There is a lack of knowledge concerning the effects of ambient heat exposure on morbidity in Northern Europe. Therefore, this study aimed to evaluate the relationships of daily summer-time temperature and heatwaves with cardiorespiratory hospital admissions in the Helsinki metropolitan area, Finland. Methods: Time-series models adjusted for potential confounders such as air pollution were used to investigate the associations of daily temperature and heatwaves with cause-specific cardiorespiratory hospital admissions, during summer months of 2001-2017. Daily number of hospitalizations was obtained from the national hospital discharge register, weather information from the Finnish Meteorological Institute. Results: Increased daily temperature was associated with decreased risk of total respiratory hospital admissions and asthma. Heatwave days were associated with 20.5% (95% CI: 6.9, 35.9) increased risk of pneumonia admissions and during long or intense heatwaves also with total respiratory admissions in the oldest age group (≥ 75 years). There were also suggestive positive associations between heatwave days and admissions due to myocardial infarction and cerebrovascular diseases. In contrast, risk of arrhythmia admissions was decreased 20.8% (95% CI: 8.0, 31.8) during heatwaves. Conclusions: Heatwaves, rather than single hot days, are a health threat affecting the morbidity even in a Northern climate.

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally. Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments. MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis. Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC. These include signaling pathways associated with mucus-secreting cell differentiation [ nuclear factor-κB (NF-кB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF). Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD. Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease. Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion.

Purpose: Determine the internal consistency and reproducibility test-retest of the Barrier Scale for Cardiac Rehabilitation (BSCR) in Colombian population. Methods: 190 patients (67% men, average age = 65 ± 12 years) completed the scale in two moments, with an average of eight days between applications. Cronbach's Alpha and Intraclass Correlation (ICC) coefficients were calculated. Results: The internal consistency of the Colombian version of the BSCR was good (Cronbach's alpha = 0.85). The ICC of the instrument was 0.69 (95% CI 0.61-0.76), 0.78 (95% CI 0.71-0.84) when used in the interview type, and 0.47 (95% CI 0, 21-0.67) when it was self-completing. Conclusions: The EBRC has an acceptable reliability in the Colombian population, however, its reproducibility decreases when it is self-directed. Identifying barriers using this scale will allow developing strategies to increase participation and adherence to cardiac rehabilitation programs focused on the real needs of patients.

During a multi-detector computed tomography (MDCT) examination, it is crucial to efficiently organize, store, and transmit medical images in DICOM standard, which requires significant hardware resources and memory. Our project processed large amounts of DICOM images by classifying them based on cross-section views that may carry important information about a possible diagnosis. We ensured that images were retained and saved in PNG format to optimize hardware resources while preserving patient confidentiality. Furthermore, we have developed a graphical, user-friendly interface that allows physicians to visualize specific regions of interest in a patient's brain where changes may indicate disease. Our proposed method enables quick classification of medical images into predefined classes of confirmed diseases of brain parenchyma, contributing to swift decision-making for further diagnosis for more precisely evaluating and characterizing brain changes, and it can lead to the rapid application of adequate therapy, which may result in better outcomes.

Periodontal diseases and Thalassemia Major (TM), which are two chronic inflammatory diseases, are associated with increased levels of proinflammatory cytokines in bio-fluids. Interleukin (IL)-6 and IL-8 have been identified as potent proinflammatory biomarkers in periodontal diseases as well as in patients with β-thalassemia (TM-β). This suggests that patients with TM-β and gingival inflammation have two chronic inflammatory conditions, each of which may affect the other. The objective of this pioneer research was to evaluate the effect of oral hygiene maintenance and care on serum levels of IL-6 and IL-8. 31 participants selected after screening and were given Non-surgical periodontal therapy(NSPT). IL-6 and IL-8 were evaluated by enzyme linked immunohistochemistry assay (ELISA) at baseline and compared at 6 weeks after NSPT. Statistical analysis was done with SPSS v23. The comparison from the baseline to 6-weeks follow-up for both IL-6 and IL-8 was done using Wilcoxon Signed rank test. The descriptive statistics are represented as median and inter quartile range (IQR). Highly significant improvement (p-<0.000) was found for IL-6 and IL-8 when compared at 6 weeks from baseline. Results provide a gateway to new modality in lowering systemic burden of the disease, thereby reducing morbidity, via local measures or oral care.

Transcription factors (TFs) and microRNAs (miRNAs) are co-actors in genome-scale decoding and regulatory networks, often targeting common genes. In this paper, we describe the algebraic geometry of both TFs and miRNAs thanks to group theory. In TFs, the generator of the group is a DNA-binding domain while, in miRNAs, the generator is the seed of the sequence. For such a generated (infinite) group $\pi$, we compute the $SL(2,\mathbb{C})$ character variety, where $SL(2,\mathbb{C})$ is simultaneously a \lq space-time' (a Lorentz group) and a \lq quantum' (a spin) group. A noteworthy result of our approach is to recognize that optimal regulation occurs when $\pi$ looks like a free group $F_r$ ($r =1$ to $3$) in the cardinality sequence of its subgroups, a result obtained in our previous papers. A non free group structure features a potential disease. A second noteworthy result is about the structure of the Groebner basis $\mathcal{G}$ of the variety. A surface with simple singularities (like the well known Cayley cubic) within $\mathcal{G}$ is a signature of a potential disease even when $G$ looks like a free group $F_r$ in its structure of subgroups. Our methods apply to groups with a generating sequence made of two to four distinct DNA/RNA bases in $\{A,T/U,G,C\}$. Several human TFs and miRNAs are investigated in detail thanks to our approach.

According to the recent data, nitric oxide (NO) is a chemical messenger that mediates functions such as vasodilation and neurotransmission, it also possesses antimicrobial and antitumoral activities. Nitric oxide has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. We searched for full-text English publications in Pubmed and SNPedia databases using keywords and combined word searches (nitric oxide, single nucleotide variants, single nucleotide polymorphisms, genes) over the past 15 years. In addition, earlier publications of historical interest were included in the review. In our review, we have sum up all NOS1, NOS2, NOS3, and NOS1AP single nucleotide variants (SNVs) involved in the development of mental disorders and neurological diseases/conditions. The results of studies we have discussed in this review are contradictory, that might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical characteristics. However, the contribution of genetic and environmental factors has been understudied, that makes this issue increasing for researchers as the understanding of these mechanisms can support a search for new approaches to pathogenetic and disease-modifying treatment.

Diabetes and chronic kidney disease (CKD) are a major public health burden in low-and-middle-income countries. This study aimed to explore factors associated with CKD in patients with type 2 diabetes (T2D) in Bangladesh. A cross-sectional study was conducted among 315 adults with T2D presenting at the outpatient department of Bangladesh Institute of Health Sciences (BIHS) hospital between July 2013 to December 2013. CKD was diagnosed based on estimated Glomerular Filtration Rate using the ‘Modification of Diet in Renal Disease’ equations and presence of albuminuria estimated by the albumin-to-creatinine ratio. Multivariate logistic regression analysis was used to determine the factors associated with CKD. The overall prevalence of CKD among patients with T2D was 21.3%. In the unadjusted model Factors associated with CKD were: aged 40-49 years (OR: 5.7, 95% CI: 1.3-25.4), age 50-59 years (7.0, 1.6-39), age ≥60 years (7.6, 1.7-34); being female (2.2, 1.2-3.8), hypertensive (1.9, 1.1-3.5) and household income between 128.2-256.4 US$ (2.9, 1.0-8.2) compared with income ≤128.2$. However, after adjustment of other covariates, only duration of hypertension and household income (128.2-256.4 US$) remained statistically significant. There is a need to implement policies and programs for early detection and management of hypertension and CKD in T2D patients in Bangladesh.

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from Surveillance Epidemiology and End Results database with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general US population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during study period. While age and surgery positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, more recent year (2001-2015) of diagnosis as well as multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM, which may be helpful for risk stratification and therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

The association between autoimmune diseases, mostly rheumatoid arthritis, systemic lupus erythematous, celiac disease and Sjögren syndrome, and lymphoma has been widely demonstrated by several epidemiologic studies. By a not yet entirely elucidated mechanism, chronic activation/stimulation of the immune system, along with the administration of specific treatments, may lead to persistent stimulation of both of B- and T-cells, and to the onset of different types of lymphoma in such patients. Specifically, patients affected by may develop lymphomas may years after the original diagnosis. Several epidemiologic, hematologic and histological factors may anticipate the progression from Sjögren syndrome into lymphoma but, to the best of our knowledge, a definite pathogenetic mechanism for such progression is still missing. In fact, while the association between Sjögren syndrome and non-Hodgkin lymphoma, mostly diffuse large B-cell and extranodal marginal zone lymphomas is well established, many other variables, such as time of onset, gender predilection, sites of occurrence, subtype of lymphoma and predictive factors still remain unclear. We report on a rare case of primary breast lymphoma occurring three years after the diagnosis of Sjögren syndrome in a 57 y.o. patient. The diagnostic work-up, including radiograms, core needle biopsy and histological examination are discussed, along with emerging data from the recent literature, thus highlighting the usefulness of breast surveillance in Sjögren syndrome patients.

KLFs seem to associate with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of differentiation of cardiac myofibroblasts or a modified fatty acid oxidation, related to the formation of a dilated cardiomyopathy; myocardial infarctions, left ventricular hypertrophy and diabetic cardiomyopathies. MicroRNA have been involved in certain regulatory loops of KLFs as they may function as critical modulators of vascular smooth muscle cells in atherosclerosis, in heart failure and as markers of endothelial damage in acute myocardial infarction.

The article is devoted to the problem of autoimmune diseases provocation by coronavirus infection and the role of molecular mimicry in this phenomenon. SARS-CoV-2 can disguise its proteins as human ones in order to avoid immune attack. A bioinformatics analysis of the probable pentapeptide sharing between human autoantigens of endocrinocytes and SARS-CoV-2 spike protein, membrane protein and nucleocapsid protein was performed. Antigen mimicry between S-proteins of all other known human Coronaviruses and typical target autoantigens of endocrinocytes was also explored. Six human-identical regions were found in the SARS-CoV-2 membrane and nucleocapsid proteins, all of them in their immunodominant epitopes. All shared epitopes belong to antigens of endocrine cells commonly targeted during autoimmune endocrinopathies. Moreover, samples of the pituitary, adrenal and thyroid from patients who died from coronovirus infection (COVID-19) were studied morphologically using histochemical methods. A high frequency of SARS-CoV-2 caused inflammation of the studied endocrine organs was found in patients who died from severe COVID-19. At the same time, the abundant expression of virus antigens by the cells of the adenohypophysis was combined with the complete absence of its expression by the cells of the neurohypophysis. SARS-CoV-2 infected cells apparently perished by non-apoptotic pathway. The foci of lesions in endocrine organs contained abundant lymphocytic infiltrates which may witness for the impact of autoimmune processes. The facts revealed emphasize the need of endocrinological diagnostic alertness of a physician while observing patients with post-vaccination and post-COVID-19 health disorders. [3 figures, 6 tables, bibliography: 45 references].

The Golgi apparatus (GA) dysfunctions in Parkinson’s Disease (PD), neurodevelopmental disorders (NDDs), cancer, and organelle structural biology (OSB) can provide insights into therapeutic targets, gene therapy, and drug design. Primary defects and fragmentation within the GA are implicated in a wide range of neurodegenerative diseases. GA defects typically result in mislocation of proteins, accumulation of undegraded proteins, and impaired glycosylation of proteins. Inhibition of vesicular trafficking by α-synuclein (aSyn) may affect the dopamine-producing neurons and neuromodulators. GA regulates apoptosis during pathological mechanisms of neurological diseases and could provide new avenues in treatments through translation research. PD patients bearing the hereditary E46K disease mutation manifest the clinical picture of parkinsonism. How do we provide high resolution nanoimages of the GA during disease to capture dysfunction? Could we visualize the aSyn traffic jam between vesicles in the organelles ER and GA? OSB is emerging as a field as more technology advances and is more accessible. Structural studies of the GA will advance the field of neurological disease forward with an in depth understanding of dysfunction, fragmentation, and defects. Discoveries of the GA in PD, NDDs, and cancer would break new ground and provide translational medicine data of these diseases. Future research could be visualizing high angle annular dark field-STEM (HAADF-STEM) tomograms, cryogenic electron tomography (cryo-ET), multiplex correlative light and electron microscopy (cryo-CLEM), nanobody-assisted tissue immunostaining for volumetric EM (NATIVE) and using soft X-ray tomography (SXT) and computational reconstruction of the GA.

Annually, millions of people worldwide are affected by skin diseases, and current therapeutic approaches have limited efficacy. Advances in the treatment of exosomes have led to the development of new therapeutic methods that hold promising potential for improving the treatment options for skin diseases. The aim of this study is to produce pharmaceutical and cosmetic compounds based on exosomes for the treatment of skin conditions such as eczema, pigmentation disorders, skin sagging and aging, cellular skin regeneration, increased skin moisture, and prevention of skin shedding, among others. This study examines the effects of exosomes derived from plants, humans, medicinal algae, and fungi to treat skin diseases. Spectrophotometric analysis reveals the presence of nucleic acids and proteins in exosome samples, indicating their cargo composition. TEM micrographs demonstrate that the exosome isolation process preserves the integrity of the membrane and the crucial spherical structure for their functionality. DLS analysis confirms that isolated exosomes have a size similar to typical exosome dimensions. MTT assays indicate concentration-dependent cytotoxic effects of exosomes on skin cells, with a calculated IC50 representing a significant decrease in cell viability. Real-time PCR shows higher gene expression levels of collagen I and collagen III, indicating the potential of exosomes to enhance collagen synthesis. Tyrosinase enzyme expression analysis demonstrates the influence of exosome treatments on pathways related to melanin production. The use of exosomes derived from various sources provides a promising platform for developing new drugs in the treatment of skin diseases. Additionally, exosomes can be utilized in the treatment of autoimmune diseases and cancer, transforming them into a hopeful field of research. Plant-derived exosomes are environmentally friendly and can serve as the next generation of drug delivery systems for treating various diseases.

MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene expression post-transcriptionally by targeting either the 3′ untranslated or coding regions of genes. They have been reported to play key roles in a wide range of biological processes. The recent remarkable developments of transcriptomics technologies, especially next-generation sequencing technologies and advanced bioinformatics tools, allow more in-depth exploration of messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) including miRNAs. These technologies have offered great opportunities for a deeper exploration of miRNA involvement in farm animal diseases, as well as livestock productivity and welfare. In this review, we provide an overview of the current knowledge of miRNA roles in farm animal diseases with a particular focus on diseases of economic importance. In addition, we discuss the steps and future perspectives of using miRNAs as biomarkers and molecular therapy for livestock disease management as well as the challenges and opportunities for understanding the regulatory mechanisms of miRNAs related to disease pathogenesis.

One in 12 babies is born with a rare genetic disease. Sadly, most cases are undetected until later age, missing time for early treatment and opportunity to prevent complications. Humanity has entered a new era where Big Data collected by governments, including 2D and 3D facial scans, are available. Many rare genetic diseases can be identified by artificial intelligence (AI) analysis of the facial photo. Phenotyping AI utilizations facilitate comprehensive and accurate genetic evaluations. AI processing of this Big Data to identify rare genetic diseases could bring unimaginable benefits to healthcare, although this would be a questionable step in terms of citizen privacy and could lead to future "Orwellian" ramifications with government abuse. Going forward, a balance must be found between protecting the privacy of citizens and the enticing use of AI for their health risks and cost savings through prevention. The unimaginable potential of AI early diagnostics from facial photos also raises various ethical and legal concerns. This paper presents concept, protentional methods and legal and other limitations within EU legal framework in contrast with potential benefits. This paper is focused on AI utilization to early diagnostic of rare genetic diseases. Shift of paradigm in the screening for rare genetic diseases in population with AI face analysis is expected to have a significant impact. The potential of AI algorithms utilizations similar to face2gene app in general population or systematically on Big governmental datasets recording facial traits changes in time can have significant impact on public health but at the same time give raise to profound concern as violation of one’s privacy.

Tick-borne diseases are a growing concern worldwide, affecting both human and animal populations. Ticks are known to harbor a wide range of pathogens and are considered one of the most important vectors of disease. Lyme disease, caused by Borrelia burgdorferi sensu lato, is the most common tick-borne disease in the US and Europe. However, accurate diagnosis of Lyme disease can be challenging due to the complex immune evasion strategies employed by Borrelia species and the limitations of existing diagnostic tests. To address this issue, researchers are exploring novel approaches, including the use of bacteriophages as diagnostic tools. Bacteriophages are highly specific and offer advantages over traditional methods for detecting bacteria, including Borrelia. In particular, the use of multicopy bacteriophages as molecular markers for Borrelia detection is a promising approach that may provide greater sensitivity than targeting single-copy bacterial genes. Nonetheless, the task of identifying trace amounts of bacteriophages in blood samples necessitates attention, and scientists are devising innovative techniques to surmount this hurdle. In summary, employing bacteriophages as a diagnostic tool for tick-borne diseases, such as Lyme disease, by specifically targeting free circulating bacteriophages in blood samples, offers significant potential for enhancing patient outcomes and public health.

Societal changes have had effects on deaths from all causes in Russia. Up until now, deaths from all causes have been well researched, although several inconsistencies persist on the contributions of researchers. This study assessed research output, trends and topics that shaped deaths from all causes studies in Russia. Using bibliometric and topic modelling approaches, deaths from all causes in Russia published from 1914 to date was analysed using data on publications, citations, journals, keywords co-occurrence, year of publication, institutional affiliations, and country of origin from Scopus. Overall results indicate a steady growth of publications in Russia was documented after 1985. The h-index of some top 10 authors did not surpass single digits. A network visualisation map showed that ‘Russia’, ‘male’, ‘mortality’ and ‘human’ were the most commonly encountered vital terms. Of the ten most prolific authors, McKee M, Shkolnikov VM, Bobak M, Samorodskaya IV and Andreev E were the first five. Although the top 10 journals researching on death causes in Russia were Russian, these journals were not included in the most cited journals. The most prolific institutions studying deaths in Russia included; Tehran University of Medical Sciences, London School of Hygiene and Tropical Medicine, University College London, Max Planck Institute for Demographic Research and National Research University-Higher School of Economics. Findings suggest that deaths from all causes research attention in Russia increased in recent years, but the number of publications and research related engagements (e.g., networking and/ collaboration) does not match-up to other countries (e.g., UK, US, Germany). This research lag calls for more collaborative research between public health disciplines and networking among researchers (i.e., both national and international).

The stability of the gut barrier is very important for keeping the gut healthy and stopping dangerous substances from getting into the bloodstream. Several diseases, including cancer, have been linked to the gut barrier being broken. Live bacteria called probiotics that are good for the host have been shown to have the ability to improve the gut barrier and lower the risk of cancer in the gastrointestinal system. This review looks at how probiotics affect the health of the gut barrier and what that might mean for preventing cancer. Researchers have found that probiotics strengthen the connections between intestine cells, encourage the production of protective mucins, and change the make-up and balance of the gut bacteria. These processes help keep the gut barrier strong and stop harmful chemicals from getting into the bloodstream. Probiotics may help lower the chance of cancer by reducing inflammation throughout the body and protecting the GI tract from harmful substances. But more study is needed to fully understand the benefits of different probiotic strains, the best amounts to take, and how they affect the health of the gut barrier. Understanding how probiotics, the health of the gut barrier, and the risk of cancer all work together can help us come up with new ways to avoid and treat cancer.

Emerging infectious disease threats require rapid response tools to inform diagnostics, treatment, and outbreak control. RNA-based metagenomics offers this; however, most approaches are time-consuming and laborious. Here, we present a simple and fast protocol – the RAPIDprep assay – with the aim to provide cause agnostic laboratory diagnosis of infection within 24 hours of sample collection by sequencing ribosomal RNA-depleted total RNA. The method is based on the synthesis and amplification of double-stranded cDNA followed by short-read sequencing with minimal handling and clean-up steps to improve processing time. The approach was optimized and applied to a range of clinical respiratory samples to demonstrate diagnostic and quantitative performance. Our results showed robust depletion of both human and microbial rRNA, and library amplification across different sample types, qualities and extraction kits using a single protocol without input nucleic acid quantification or quality assessment. Furthermore, we demonstrate the genomic yield of both known and undiagnosed pathogens with complete genomes recovered in most cases to inform molecular epidemiological investigations and vaccine design. The RAPIDprep assay is a simple and effective tool, and representative of an important shift towards integration of modern genomic techniques to infectious disease investigations.

Bacteriophages are viruses obligately infecting bacteria. They constitute the most numerous categories of biological forms populating our biosphere and are highly diverse and capable of infecting almost all bacteria. Phages make use of their host cell molecular machinery to express their own genes as they lack the ability to independently reproduce themselves. The inimitable characteristics of bacteriophages have enabled them to become propitious tools in biotechnology and genetic engineering. Phages show no tropism for mammalian cells but however, can be easily modified to present targeting ligands on their surface as coat protein fusions without any negative impacts on phage structure. These displayed ligands thereupon guide the recognition, interaction, and internalization of the phage into cells wherein efficiency of transfection is directly influenced by the copy number of the ligands used for targeting. Engineered phages are more efficacious for transgene delivery and gene expression in cancer cells when compared to other non-viral gene transfer strategies and are therefore being employed in developing cancer vaccines. The high level of stability as well as resistance of bacteriophages to various environmental conditions have enabled the development of virus-like particles (VLPs) capable of successful deliverance of several therapeutic drug cargos into tumors by selective targeting. Phage display technology has been used in therapy of Alzheimer’s disease and drug delivery into the brain. Exogenous peptides fused into the coat protein of phages enables the display of these peptides on the phage surface to generate combinatorial phage that facilitates their rapid separation using their ability to bind to a specific molecular target. Phage therapy has been shown to be safe in clinical settings when compared to antibiotics as it shows no adverse anaphylaxis nor adverse effects such as the emergence of multi-drug resistant bacteria. This review provides intriguing details of the use of natural and engineered phages in the therapy of diseases such as cancer, bacterial infections, bovine mastitis and dementia in addition to the use of CRISPR-Cas9 technology in generating genetically engineered phages. Further, the use of phage display technology in generating monoclonal antibodies against various human diseases is elucidated.

Background: When we talk about zoonoses, it is undeniable that we have a human and animal population that has been isolated in studies over time. Besides human and animal health, zoonoses also impact the economy and society. Therefore, the integration of the analysis in this area is essential to optimize resources in public health decisions. We have new challenges in public health that we need to overcome in a more comprehensive method such as One Health. For better measures in public health, the dual burden of zoonoses seems a logical way to determine the integral impact of such diseases in society and thus take better measures to prevent and reduce the impact of these diseases. Methods: We follow the guidelines for “Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). We search human and animal zoonoses on Embase, Ovid Medline, Scopus, Web of Science, and Google Scholar, from an unrestricted period until November 2021. For the search, we consider the Disability Adjusted Life Years (DALYs) for the human zoonotic burden and the animal zoonotic burden in monetary terms. A librarian collaborates to optimize the search string for the databases, and two reviewers screen eligible articles (first by title, then by abstracts, and finally, by full-text assessment.) For the analysis, we aim to convert the burden of zoonoses of all selected studies into the zoonotic Disability Adjusted Life Years (zDALYs) – including the human and animal components. Discussion: The study results will provide information on published studies that have accounted for the dual burden of zoonoses (both human and animal health aspects.) In addition, the synthesis of the available literature will address the knowledge gap in this area in order to know to what extent it is possible to convert the burden of human zoonoses to the animal burden of zoonoses and integrate them into a more comprehensive approach (dual burden of zoonoses.)

Our recent work has focused on the application of infinite group theory and related algebraic geometric tools in the context of transcription factors and microRNAs. We were able to differentiate between “healthy" nucleotide sequences and disrupted sequences that may be associated with various diseases. In this paper, we extend our efforts to the study of messenger RNA metabolism, showcasing the power of our approach. We investigate (i) mRNA translation in prokaryotes and eukaryotes, (ii) polyadenylation in eukaryotes, which is crucial for nuclear export, translation, stability, and splicing of mRNA, (iii) miRNAs involved in RNA silencing and post-transcriptional regulation of gene expression, and (iv) the identification of disrupted sequences that could lead to potential illnesses. To achieve this, we employ (a) infinite (finitely generated) groups fp, with generators representing the r+1 distinct nucleotides and a relation between them [e.g., the consensus sequence in the mRNA translation (i), the poly(A) tail in item (ii), and the miRNA seed in item (iii)], (b) aperiodicity theory, which connects “healthy groups" fp to free groups Fr of rank r and their profinite completion F^r, and (c) the representation theory of groups fp over the space-time-spin group SL2(C), highlighting the role of surfaces with isolated singularities in the character variety. Our approach could potentially contribute to the understanding of the molecular mechanisms underlying various diseases and help develop new diagnostic or therapeutic strategies.

The accumulation of loss of function mutations in the uricase gene well explains the high urate levels in hominoids (apes and humans) compared to other mammals. The loss of human uricase activity may have allowed humans to survive environmental stressors, evolution bottlenecks, and life-threatening pathogens. While high urate levels may contribute to developing cardiometabolic disorders such as hypertension and insulin resistance, low urate levels may increase the risk for neurodegenerative diseases. The double-edged sword effect of uric acid has resurrected a growing interest in the antioxidant role of urate and the role of the uricase gene in modulating the risk of obesity. Characterizing both the effect of uric acid levels and the uricase gene in different animal models may provide new insights into the potential therapeutic benefits of uric acid and novel uricase-based therapy.

In this article, we describe an immunochromatographic test system developed for rapid serodiagnostics of cattle brucellosis using two markers: gold nanoparticles (GNPs) and quantum dots (QDs). The test system was compared with immunochromatographic serodiagnostics systems that use only one marker. The approbation of the test system was conducted on samples of cattle sera with low, but diagnostically significant titers of specific antibodies. We show that when two conjugates are used, the intensity of the detectable signal increases by 2–3 times compared with the test system using the QD conjugate and by more than 9 times compared with the system using the GNP conjugate.

miRNAs have recently attracted investigators' interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors comprise of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

Immune-mediated bowel diseases (IMBD), including Ulcerative colitis and Crohn's disease, represent a significant global health burden with their complex etiology and increasing prevalence. The connection between intestinal parasites and the gut microbiome in immune-mediated bowel disease is a complex and evolving field of research. Several studies have demonstrated that intestinal parasites can modulate the composition and function of the gut microbiome. Parasitic infections can result in alterations in the gut microbial community, including changes in microbial diversity, abundance, and metabolic activity. These changes can influence the immune response and contribute to the development of IMBDs. In contrast, the gut microbiome serves a pivotal function in maintaining intestinal homeostasis and immune regulation. Dysbiosis, characterized by changes in the gut microbial composition, has been associated with the pathogenesis of IMBDs. Imbalances in the gut microbiota can result in increased gut permeability, chronic inflammation, and aberrant immune responses, all of which are hallmarks of IMBDs. The bidirectional interaction between intestinal parasites and the gut microbiome further complicates the understanding of immune-mediated bowel diseases. Certain parasites, such as hookworms and Necator americanus, have been found to downregulate immune responses and may have therapeutic potential in treating celiac disease. On the other hand, infections with parasites like Strongyloides stercoralis and Blastocystis have been shown to mimic the symptoms of IBD, highlighting the intricate relationship between parasites and the pathogenesis of these diseases. Additional investigation is required to comprehensively elucidate the mechanisms that underlie the association between intestinal parasites and the gut microbiome in immune-mediated bowel disease. This knowledge could potentially lead to the development of targeted therapeutic strategies that aim to restore gut microbiota homeostasis and alleviate the symptoms of these debilitating conditions. By understanding and harnessing the complex interplay between parasites, the gut microbiome, and the host immune system, researchers may uncover novel approaches for the management and treatment of immune-mediated bowel diseases.

There is a need to further characterize the antibody response to vimentin in relation to it possible involvement in pathogenicity of sarcoidosis, and other lung disorders. Objectives: We investigated serum samples from patients with sarcoidosis, healthy and diseased control subjects to evaluate levels and frequency of these antibodies. Materials and methods. A retrospective-prospective comparative study was performed in the years 2014-2017. 188 serum samples were examined for presence of autoantibodies to mutated citrullinated vimentin (anti-MCV). Patients with elevated anti-MCV levels were tested for antibodies to a cyclic citrullinated peptide (anti-CCP) and citrullinated vimentin (anti-Sa). Additionally, sera from 93 patients with sarcoidosis and 40 healthy subjects were evaluated for the presence of autoantibodies to non-modified vimentin. In all cases ELISA assays was used. The results were considered statistically significant at p-value less than 0.05. Results of the study. The high concentrations of anti-MCV. antibodies were more frequent in patients with sarcoidosis (40.9% of the cases, 38/93), compared to the control groups (23.6% and 25.0% of cases, respectively). In sarcoidosis, clinical symptoms similar to the autoimmune pathology were described. A moderate positive correlation between the anti-MCV and anti-Sa antibodies (r = 0.66) was found in 13 patients with sarcoidosis. There was no significant difference between the levels of the anti-MCV and the anti-CCP in patients with non-infectious lung diseases and the healthy control group. Conclusion. A high level of anti-MCV antibodies in patients with sarcoidosis characterizes the presence of an autoimmune process that is not related to citrullination. The absence of a significant difference in the level of antibodies to modifications of vimentin in patients with sarcoidosis may indicate the autoimmune process.

The rising incidence of complex illnesses and their costs have revolutionized basic research, patient management, and societal needs. Between 70 to 90% of the risk of developing a disease is due to the air we breathe, the water we drink, and the surroundings in which we work and live. Visibly polluted, infectious or not, the fact remains that we are more than ever exposed to environmental risks. Air pollution is the fourth most prevalent deadly risk factor worldwide and by far the leading risk factor for hundreds of diseases, including respiratory infections, inflammatory illness, and cancer. Thus, an unhealthy environment can be considered as a pandemic, affecting 280 million people and claiming 12 million deaths every year. Although critical for identifying of the people at risk, the causal environment components (pollutants and/or the microbiome), and the affected physiological mechanisms are not well understood. Herein, we consider the dysregulation of macroautophagy (hereafter referred to as ‘autophagy’), as the mechanism at the heart of an immediate response to environmental stress. We discuss the missing link between the autophagy gene variations, and the exposome in the susceptibility, prognosis, and management of complex diseases when embracing personalized medicine.

Although originally multi-ethnic in its structure, nowadays the Calabria region of southern Italy represents an area with a low genetic heterogeneity and a high level of consanguinity that allows rare mutations to be maintained due to the founder effect. A complex research methodology ranging from clinical activity to genealogical reconstruction of families/populations along the centuries, creation of databases, and molecular/genetic research, has been modelled on the characteristics of the Calabrian population for more than three decades. This methodology allows to the identification of several novel genetic mutations or variants associated with neurodegenerative diseases. In addition, in this population it has been reported a higher prevalence of several hereditary neurodegenerative diseases such as Alzheimer’s disease, Frontotemporal dementia, Parkinson’s disease, Niemann Pick type C disease, Spino-cerebellar ataxia, Creutzfeldt–Jakob disease and Gerstmann Straussler Scheincker disease. Thus, Calabria constitutes a model for the study of neurodegenerative diseases, a sort of "outdoor laboratory" useful for the advancement of knowledge in this field. Here, we summarize and discuss some results of research data supporting the view that Calabria is a genetic isolate and could represent a useful model for the study and characterization of neurodegenerative diseases.

The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, that could facilitate the development of interventions contributing to “successful aging” and improvement of quality of life. Cardio-vascular diseases (CVD) include pathologies affecting heart or blood vessels, such as hyperten-sion, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations raising the risk of CVD development. Several factors have been claimed to play a role in the alterations observed in muscle and endothelial cells and leading to increased CVD, such as genetic pattern, smoking, unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the last decades attention has been focused on a potential role of several pollutants which disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatic process and CVD progression.

Probiotics are namely yeast and bacteria which are regarded as dietary supplements and food. Many probiotics are being commonly used now, the most frequently used, lactic acid bacteria are called Lactobacillus and Bifidobacterium. Many of the diseases associated with GIT are related to microbiota found in GIT, an imbalance of which causes gastrointestinal diseases. Probiotics, in light of scientific literature, are thought to play an important role in relieving symptoms of many diseases associated with GIT, i.e. beneficially regulating the microbiota composition. In the present review, we aimed to highlight the main considerations for main probiotic formulations to date. This study reviews the role of different probiotic formulations introduced so far in treating GI diseases in cohort ageing ≤18 years. We searched PubMed and Clinicaltrials.gov without any restrictions. This study comprises the descriptive and comparative analysis between Single-organism and Composite probiotics. These GI diseases include NEC, FAP, AGE, Acute Diarrhea, Ulcerative Colitis and etc. The results have been categorized according to title and outcomes. The positive outcomes emphasize the drug’s effectiveness in improving health and the negative outcome elaborates on the adverse effects the drug may have shown. Conclusively, discussed practices will assist in reducing GI disorders and strengthening the gut. Further insight into the various gut microbes and microbiomes with specific demographic is recommended.

Rodents are known to be reservoirs of Toxoplasma gondii and keep the parasite circulation in the environment. We conducted biomonitoring to assess the role of sylvatic rodents in maintaining T. gondii and to analyse the prevalence and seroprevalence of the parasite in seven wild rodent species. Rodents were collected in our study sites (woodland and open grasslands) located in northeastern Poland and dissected. We collected brain, spleen, blood and serum samples. We applied both molecular (PCR assay, nested-PCR assay) and serological (ELISA and agglutination tests) methods to indicate the best approach for application in the biomonitoring of T. gondii in small mammals. We screened samples from 95 individuals sing PCR assays and found no T. gondii DNA. The agglutination test showed no signal. We found antibodies against T. gondii in 6 sera samples out of 74 analysed (seroprevalence = 8.11% [4.0-17.1]). Our results confirm that rodents participate in the life cycle of T. gondii as reservoirs of this parasite in the sylvatic environment. However, biomonitoring should be performed with the ELISA tests to search for T. gondii antigens, rather than a molecular approach only.

Aquaculture is rapidly becoming one of the pivotal sectors in the farm economy, driven by the increasing demand for high-quality animal protein at an affordable cost, especially with the escalating human population. However, the expansion of high-density fish populations also brings forth a challenge – the rapid transmission and spread of infectious disease agents among them. To combat this, vaccination is emerging as a reliable and standardized method for providing immunity against viral and bacterial outbreaks. The ideal vaccine is expected to be safe, effective, economical, and easily administered. The fish vaccination industry continually publishes new information on fish immunology and vaccinology, contributing to the improvement of vaccine formulation and efficacy. This review aims to offer insights into the current status of bacterial, viral, and parasitic diseases, discuss existing vaccinations, and address potential industry-threatening diseases like infectious edwardsiellosis, motile aeromonas septicemia, TiLV, salmon anemia, vibriosis, and white spot disease. Technological advancements have played a crucial role in enhancing our understanding of fish immunological mechanisms, leading to improved vaccine administration and the development of recombinant live attenuated, subunit, DNA, and RNA vaccines. However, challenges such as oral tolerance, vaccine degradation, and stressful environments persist, impacting vaccine efficacy. Addressing these challenges and gaining a deeper understanding of the fish immune system and host-pathogen interactions will be pivotal for future improvements, contributing to the sustainability of aquaculture and enhancing global food security.

Globally, noncommunicable diseases (NCDs) were responsible for 41 million deaths in 2016, with the majority of these occurring in low and middle-income countries. These diseases were on the rise as a result of unhealthy, low-quality, and unbalanced diets, which resulted in overweight and obesity. The National School Nutrition Programme (NSNP) was created to regulate the foods sold to schoolchildren. To ascertain school management teams' perspectives on the relationship between the NSNP and the development of lifestyle diseases. A phenomenological qualitative study using Focus Group Discussions among 16 purposively selected members of the School Management Teams were conducted in Mt Frere, Eastern Cape in 2016. The narrative data was analyzed using Tesch's eight-phase thematic analysis approach. The data analysis revealed two themes (NSNP and the vendor system) and six sub-themes. The NSNP was viewed as making a significant contribution to children's food security, thereby improving academic output. However, reengineering of the NSNP was need through improved budgeting and inclusion of breakfast in the menu to control NCDs risk factors. The current implementation of the vendor system did not support reduction of NCDs risk factors. Improved implementation of the guide to vendor system is needed.

In Africa, vector-borne diseases (VBDs) are still a major public health issue especially in cities that gather an increasing human population. Market gardening practices, for example, can favor the transmission of urban malaria, while insufficient water supply and waste management favor the circulation of arboviroses related to Aedes mosquitoes. Urban planning is a major challenge to mitigate vector risks. As a planning strategy, greening is a concept that is increasingly considered as a major element impacting the well-being of inhabitants, but also for the restoration of biodiversity in cities. Nevertheless, the impact of urban green spaces on vector risk remains poorly investigated, as they may serve as refuge for vectors. This is why the diversity of mosquitoes in terms of species and larval habitat, through larval prospections in environmental water collections and human landing catches, is studied here at an intra-urban interface area between a forest and an urban ecosystem in order to assess the vector risk generated by preserving a forest patch in the heart of Libreville, capital of Gabon, central Africa. Out of 104 water containers explored, 94 (90.4%) were artificial, mainly comprising gutters, used tires, and plastic bottles, while 10 (9.6%) were natural, comprising a puddle, streams, and tree holes. The majority of the water collections recovered (73.1%) were found outside of the forested area, natural and artificial ones considered together. A total of 770 mosquitoes belonging to 14 species were collected from water collections. The mosquito community was largely dominated by anthropophilic species like Aedes albopictus (33.5%), Culex quinquefasciatus (30.4%), and Lutzia tigripes (16.5%). The Shannon index of diversity showed that mosquitoes were almost twice less diversified inside the forest (0.7) than outside (1.3). However, both communities were quite similar in terms of common species and relative abundance (Morisita-Horn index = 0.7). Regarding Human landing catches, Aedes albopictus (86.1%) was the most aggressive species, putting people at risk of Aedes-borne viruses. This study uncovered the importance of considering urban forested ecosystems as potential drivers of disease emergence and spread in urban areas, as they might locally boost urban mosquito densities due to poor environmental practices, mainly maintained by humans through poor environmental practices. In Gabon, this study should contribute to guide targeted vector control strategies, especially regarding the implementation of policies for a better environmental management and vector surveillance in urbanized areas.

Intramammary infections (mastitis) of dairy cows, along with other periparturient diseases, have become problematic within the dairy industry as they lead to loss of milk production. The main objective of this study was to determine whether elevated somatic cell counts (SCC) in cows prior to drying off are related to the incidence of other periparturient diseases. Additionally, we de-termined whether milk composition and milk yield are affected by a high SCC prior to drying off. Somatic cell counts of milk samples were determined prior to dry off (n = 140) and were used to classify cows in the study as high (>200,000 cells/mL) or low (<200,000 cells/mL) SCC. The com-position of milk was analyzed before drying off and at 1 and 2 weeks after calving. The results showed that an elevated SCC before drying off was related to the incidence of ketosis. Cows with a high SCC at drying off also showed an increased likelihood of retained placenta, metritis, and lameness postpartum; however, it was not statistically significant. Milk lactose was lower in cows with high SCC, while protein content was lower after parturition. Milk production was lower for cows with pre-drying elevated SCC, particularly for cows with retained placenta, keto-sis, and mastitis. In conclusion, cows with pre-drying elevated SCC were more likely to develop disease after parturition and produce less milk and with lower lactose and protein content.

The sustainable development goals(SDG) of the UNO would be difficult to achieve without prevention of metabolic diseases and other non-communicable diseases (NCDs). Western diet and lifestyle, which are major risk factors of NCDs, are known to cause oxidative stress and decrease in production of molecular hydrogen in the intestines which leads to a decline in endogenous antioxidant status in the body, leading to increase in systemic inflammation. Many experts consider molecular hydrogen as a potential nutrient, which may be administered as gas in the body. There are gaps in the knowledge about the role molecular hydrogen plays, in the treatment of metabolic diseases and other NCDs This review aims to discuss the role of hydrogen in the pathogenesis and prevention of NCDs. Molecular hydrogen (H2) has been studied extensively as a therapeutic gas, with an estimated 2000 publications to date, exploring its potential therapeutic use in 170 disease models across every organ in the mammalian body. Hydrogen therapy can be administered through several methods, such as H2 inhalation, dissolving H2 gas in water to make hydrogen-rich water (HRW) for oral consumption or topical application, or hydrogen-rich saline. The exact mechanism of action of molecular hydrogen is not known but it is in itself a potential antioxidant that can also inhibit hydroxyl and nitrosyl radicals in the cells and tissues. Hydrogen is known to cause a marked decline in oxidative stress, and inflammation that are crucial in the pathogenesis of NCDs. Hydrogen therapy has been found protective against NCDs, including, metabolic diseases, cardiovascular diseases (CVDs), neurodegenerative diseases, chronic kidney disease, cancer and chronic lung diseases.

Artificial intelligence (AI) is revolutionizing approaches in plant disease management and phy-topathological research. This review analyzes current applications and future directions of AI in addressing evolving agricultural challenges. Plant diseases annually cause 10-16% yield losses in major crops, prompting urgent innovations. Artificial intelligence (AI) shows aptitude for auto-mated disease detection and diagnosis utilizing image recognition techniques, with reported accuracies exceeding 95% and surpassing human visual assessment. Forecasting models inte-grating weather, soil, and crop data enable preemptive interventions by predicting spa-tial-temporal outbreak risks weeks in advance at 81-95% precision, minimizing pesticide usage. Precision agriculture powered by AI optimizes data-driven, tailored crop protection strategies boosting resilience. Real-time monitoring leveraging AI discerns pre-symptomatic anomalies from plant and environmental data for early alerts. These applications highlight AI's proficiency in il-luminating opaque disease patterns within increasingly complex agricultural data. Machine learning techniques overcome human cognitive constraints by discovering multivariate correla-tions unnoticed before. AI is poised to transform in-field decision making around disease pre-vention and precision management. Overall, AI constitutes a strategic innovation pathway to strengthen ecological plant health management amidst climate change, globalization, and agri-cultural intensification pressures. With prudent and ethical implementation, AI-enabled tools promise to enable next-generation phytopathology, enhancing crop resilience worldwide.Artificial Intelligence, Phytopathology, Emerging Disease, Climate Change, Control diseases.

Cells produce reactive oxygen species (ROS) as by-products of metabolism, which can give rise to a two-sided effect on the body under balanced and imbalanced oxidant homeostasis conditions. Antioxidant supplements exert their beneficial efficacy in the treatment of metabolic diseases only when the oxidant homeostasis is imbalanced with the over-production of ROS. Over-supplementation of antioxidant(s) can also cause an imbalanced oxidant homeostasis to exert detriments to the induction of metabolic diseases. This commentary raises a concern that prior to precise supplementation of antioxidants, an establishment of oxidant homeostasis status is required in avoiding an imbalanced oxidant homeostasis in vivo. In searching for valid oxidant stress makers, 3-Nitrotyrosine seems to fit in with the selection criteria and its quantification can be correlated with the degree of oxidative stress in vivo.

Matrix metalloproteinases are involved in extracellular matrix remodeling through the degradation of extracellular matrix components and are involved in the inflammatory response by regulating the activities of TNF-alpha and IL-1beta, which are pro-inflammatory cytokines, in addition to extracellular matrix components. Since the regulation of inflammatory response and changes in the extracellular matrix by MMPs are related to the development of various diseases including lung and cardiovascular diseases, many studies have been conducted on the role of MMPs in pathogenesis. In addition, various studies have demonstrated that MMPs are involved in the pathogenesis of infectious diseases by regulating the expression and activity of MMPs by infection with pathogens. In this review, we discuss the role of MMPs in infectious diseases and the role of MMPs in inflammatory responses and present their potential as therapeutic targets in infectious diseases.

Obesity is related to the establishment of chronic inflammation and metabolic diseases, but it can be positively influenced by the regular practice of physical activity. The study aimed to compare the anthropometric, metabolic, and inflammatory parameters of physically active Military Police Officers (MPOs) with those who are less physically active. Sixty male MPOs, low activity (n=28) and physically active (n=32) participated. The following parameters were measured: plasma cytokine levels, C-reactive protein (CRP) levels, circulating glucose triglyceride (TAG) and high-density lipoprotein cholesterol (HDL-C) levels, and plasma glutamic oxalacetate transaminase (GOT), glutamic-pyruvate transaminase (GPT), and gamma-glutamyl transferase (GGT) activities. The physically active group presented lower body fat and reduced TAG and IL-8 levels compared to the low activity group. Moreover, a negative correlation between SPE and SBP, DBP, BPM was detected for the physically active group (p<0.05) but not in the low activity group. Furthermore, the physically active group's work time (WT) values were not correlated with the important metabolic markers SBP, DBP, BPM, GLU, TAG (p>0.05) but could be in the low activity group (p<0.05). These findings highlight the fundamental protective role of physical activity in controlling body composition, subclinical inflammation, and cardiovascular risk in MPOs.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering.’

The diagnosis and treatment of autoimmune diseases are major challenges. Their signs, symptoms, and their clinical severity change throughout the course of the disease. The available treatments for these conditions do not result in complete remission, and their long-term use generates several side effects. The main challenges in this field are the development of more sensitive diagnostic tools, and effective treatments. Studies in patients and animal models reported alterations in monocyte phenotype, activation, and function. These cells play an essential role in the pathogenesis of chronic inflammatory states and have become a target for extracorporeal monitoring and specific intervention. Nanoparticles (NPs) are ultrafine particles that can be used as contrast agents in diagnostic imaging techniques to detect specific cells in inflammatory infiltrates in tissues that are not easily accessible by biopsy. In addition, NPs can be designed to deliver drugs to a cell population or tissue. This review describes several experimental pieces of evidence demonstrating that monocytes and macrophages can specifically uptake various types of NPs, thus becoming detectable in vivo by magnetic resonance imaging and susceptible to be modulated by therapeutic agents. Hence, nanoparticles targeting mononuclear phagocytes represent promising tools for diagnosing and treatment.

Acute kidney injury (AKI) is a complication that can occur after cardiac surgery and requires ongoing research in light of the exponential expansion of technological advancements and knowledge in medicine. In this study, we aim to evaluate the outcomes of treated electives of emergency aortic disease with high serum creatinine levels (SCr). Methods: The cohort includes 183 patients, all of whom have an aortic disease and whose SCr levels were checked upon admission on the first day in the intensive care unit (ICU) and upon discharge from the hospital. We examined the correlation of SCr levels with in-hospital mortality and immediate mortality at least six months after discharge as well as with cross-clamp time and bypass time.Results: A high SCr level upon admission is a significant predictive factor of n-hospital mortality (p = 0.001) but not immediate mortality (p = 0.409). A statistically significant correlation was also observed between elevated SCr level on the first day of ICU and aortic disease (p = 0.041) but not immediate mortality (p = 0.119). We observed a significant correlation between aortic disease and in-hospital mortality (p < 0.001), but no correlation was found between high SCr level on the first day of ICU and immediate mortality (p = 0.119). The cross-clamp time is statistically significant correlated with elevated SCr level (p = 0.013) and in-hospital mortality (p = 0.001) but not immediate mortality (p = 0.847). Furthermore, the bypass time is negatively correlated with a high SCr level on the first day of ICU (p = 0.090), in-hospital mortality (p = 0.410), and immediate mortality (p = 0.625). We also found that aortic disease is not correlated with elevated creatinine levels at ICU discharge (p = 0.152) or long-term mortality (p = 0.106). Conclusions: Although this study only included a small portion of the elaborate aspects of surgical and medical management developed around cardiac patients who received invasive treatment, the conclusions reached are nevertheless clearly relevant, as evidenced by the significantly correlations uncovered. In order to manage AKI after AAS and improve the outcome, the SCr level could be used as a marker for renoprotective strategy. Moving forward, these results serve as a first step in motivating us to expand the range of our research, collect newly relevant data, and use it to benefit patients.

Magnetic Nanoparticles (MNPs) is a promising technique to cure brain diseases. On the one hand, by serving as drug carriers, they can bypass the blood-brain barrier and deliver drug molecules to the brain parenchyma; on the other hand, their transport trajectory can be manipulated by applying an external magnetic field. However, due to the complex microstructure of brain tissues, e.g. the anisotropy of white matter (WM), how to achieve desired drug distribution patterns, e.g. uniform distribution, by tuning the drug delivery system is largely unknown. Here, in this study, by adopting a mathematical model capable of capturing the diffusion trajectories of MNPs in the microstructures, we systematically investigated the effects of key parameters in the MNPs delivery system on the equivalent diffusion coefficient of MNPs in the microenvironment of brain WM. The results show that uniform distribution of MNPs in anisotropic tissues can be achieved by adjusting the particle size and magnetic field. We have not only obtained a deeper understanding on how to optimise the MNPs delivery system, it can also be anticipated that an improved mathematical model could even help to achieve complex drug distribution patterns in the complicated brain environment by designing an appropriate combination of the key parameters.

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but literature on long-term recovery of young adults after mild-to-moderate infection is lacking. Heart rate variability (HRV) allows observation of autonomic nervous system (ANS) modulation post SARS-CoV-2 infection. Additionally, physical activity (PA) helps improve ANS modulation, where investigation of PA influence on ANS recovery is vital to reduce risk and severity of symptoms. Clinicians may use this research to aid development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were observed where general amnamnesis was performed, followed by HRV and PA assessment. 10 CT and 7 PCOV subjects returned for follow-up (FU) evaluation 6 weeks after complete immunization (2 doses) and assessments were repeated. Over the follow-up period, decrease in sympathetic (SNS) activity (mean heart rate: p=0.0024, CI=-24.67- -3.26; SNS index: p=0.0068, CI=-2.50- -0.32) and increase in parasympathetic (PNS) activity (mean RR:p=0.0097, CI=33.72-225.51; PNS index: p=0.0091, CI=-0.20-1.47) were observed. At follow-up, HRV was not different between groups (p>0.05). Additionally, no differences were observed in PA between moments and groups. This study provides evidence of ANS recovery after SARS-CoV-2 insult in young adults over a follow-up period, independent of changes in PA.

We report the first correction by Prime editing of a mutation in the RYR1 gene, paving the way to gene therapies for RYR1-related myopathies. The RYR1 gene codes for a calcium channel named Ryanodine receptor 1, which is expressed in skeletal muscle fibers. The failure of this channel causes muscle weakness in patients, which degenerates into motor disabilities. Currently, there are no effective treatments for these diseases, which are mainly caused by point mutations. Prime editing allows the modification of precise nucleotides in the DNA. Our results showed a 59% correction rate of the T4709M mutation in the RYR1 gene in human myoblasts by RNA delivery of the Prime editing components. It is to be noted that the T4709M is recessive, and thus, persons having a heterozygous mutation are healthy. These results are the first demonstration that it is possible to correct mutations in the RYR1 gene.

Neurodegenerative diseases like Alzheimer's diseases are irreversible, progressive, and refractory in nature and managed very poorly. AD is manifested with the aggregation of unfolded proteins, synaptic pathology and dementia and poses challenges to the health care system globally. Only very few treatments with minimal effect are available to the patients and their caregivers. Despite numerous clinical trials which were launched for AD, unfortunately, most of them failed in satisfying the pharmacological criteria. At cellular levels, many signaling pathways have been proposed for the sterile / refractory behavior of degenerating neurons. Among those, Mitogen activated protein kinases (MAPKs) are the critical cellular networks which are involved in the development of Alzheimer’s disease. Several studies have demonstrated a favorable impact of MAPK inhibition on inflammatory programming, synaptic plasticity, and memory problems in mouse models of AD. In view of this, various clinical trials were launched with several MAPK inhibitors (with good safety profile and less side-effects) have yielded positive results in AD patients suggesting that MAPK targeting may be effective for reducing the pathogenesis of AD, but due to selectivity, dosing and patient stratification, this aspect still need development. In view of selectivity and off-target effects, only a few MAPK inhibitors have been employed in clinical trials against AD indicating a scope of development in this area. Therefore, this study focuses on MAPK based interventions as an upcoming and innovative approach for alleviating AD with special emphasis on clinical studies.

Brachycephalic dogs are not only affected by brachycephalic obstructive airway syndrome (BOAS), but also comprise up to 30% of canine patients seen by veterinary dermatologists, with English Bulldogs and Pugs particularly overrepresented. Some skin diseases are associated with the abnormal anatomic conformation of brachycephalic dogs, while for others there is a underlying genetic basis or a general predisposition. Anatomic alterations associated with brachycephaly, leading to fold formation of the skin and stenosis of the ear canal, together with primary immunodeficiencies described in some breeds, favor the development of pyoderma, Malassezia dermatitis and otitis externa/media. Frequently neglected but often lifelong dermatological problems of brachycephalic dogs are an important consideration when discussing genetic and medical conditions affecting the welfare of those dogs. Here we review the current state of knowledge concerning dermatological problems of brachycephalic dogs, and combine it with clinical experience in the management of these challenging disorders.

Climate change, recognized as a global crisis, is not only altering our environment but also significantly impacting human health. Particularly, its influence on non-communicable diseases (NCDs), a leading cause of global mortality, is becoming increasingly evident yet underexplored. This review aims to synthesize current research on the impact of climate change on NCDs, addressing a critical gap in our understanding of how environmental changes affect human health. We examine the complex interplay between climate change and NCDs, drawing insights from recent studies that highlight the adverse effects of climate variables on chronic diseases, such as cardiovascular and kidney diseases, and the role of food and nutrition security in this nexus. Furthermore, the review explores the disproportionate impact on vulnerable regions and populations, particularly in Pacific Island countries and territories, underscoring the urgent need for context-specific solutions and a cross-sectoral approach. By integrating findings from various disciplines, this review aims to inform policy and public health interventions, highlighting the necessity of collaborative efforts to mitigate the burgeoning burden of NCDs in a rapidly changing climate.

The evolving global SARS-CoV-2 pandemic emphasizes how unprepared we are for the emergence of the next lethal viral pathogen. A list of potential candidates was created by the World Health Organization which named Nipah virus infection as the highly lethal prototypic member of that list. Building on our earlier viral pandemic preparedness research into SARS-CoV-2 we have created computer simulations of Nipah virus infection complicated by encephalitis, the most common cause of Nipah-associated mortality. In the current experiments, we first created updated simulations of wild-type whole-brain organoids (aiWBO). Upon validation, the aiWBO were infected with the simulated Nipah virus genome. The Nipah encephalitis simulations (aiWBO-NiV) were then used to find optimal single, double, and triple protein combinations for candidates as potential targets for vaccine development. Our data suggest that the use of multi-viral proteins/epitopes chimera is the most promising approach to Nipah vaccine development and that employing artificial intelligence to guide the identification of promising vaccine candidates is an efficient and cost-effective strategy for future viral pandemic preparedness.

Older adults in low-and middle-income countries experience a disproportionate burden of non-communicable diseases (NCDs). Unintentional injuries are among the major NCDs, and falls are the second leading cause of these injuries and deaths worldwide, including in Thailand. We aimed to culturally adapt the CDC’s Stopping Elderly Accidents, Deaths, and Injuries (STEADI) for Thai older adults and explore the feasibility, appropriateness, and acceptability of using STEADI in primary care via trained community health workers (CHWs) and care managers (CMs). STEADI takes a coordinated care approach that consists of three steps: screening, assessing, and intervening. In Step a, CHWs screened fall risk in 20 community-dwelling older adults using three key questions and found that all of them had fall risk, then CHWs screened with a Stay Independent questionnaire (range 0-14) and found that 100% have high fall risk (total scores 9.7± 2.4). In Step b, CMs assessed balance, vision, footwear, postural hypotension, medications, and CHWs assessed home hazards. They found that 50% had poor balance, 70% took 4+ medications,75% fell on the walkway, and 70% had no bathroom modifications. In Step c, individual participants received fall prevention interventions to mitigate their specific fall risk factors. CHWs and CMs indicated high acceptability (19.20±.1.31 of 20 total), appropriateness (18.80± 1.79 of 20 total), and feasibility (18.60±1.67 of 20 total) of the Thai-STEADI intervention. Our study showed that the community-based multifactorial Thai-STEADI delivered by CHWs and CMs is feasible and acceptable to prevent falls in older adults with limited access to health care.

Global agriculture has been forced to increase food production to feed the growing human population, while confronting various environmental obstacles such as global warming, resistance to pathogens, and constraints on arable land caused by soil salinity, drought, rising sea level, saltwater intrusion, and urbanization. Regarding abiotic stresses, salinity is a worldwide problem for agricultural production. Many efforts, therefore, have been made to cope with the environmental challenges, however, the progress of salinization, which is mainly caused and accelerated by anthropogenic activities, is likely faster than our progress in finding ways to deal with this problem. In addition, drought represents a global threat to the production of major crops. In addition, pests and pathogens cause significant crop losses and diminish global food security. Among the various strategies that have been investigated and applied in plant science, antimicrobial peptides derived from plants have caught widespread attention from scientists since these peptides exhibit beneficial biological activities. In agricultural science, there have been reports on the roles of antimicrobial peptides with active properties against biotic and abiotic stresses. Non-specific plant lipid transfer proteins, thionins, systemins, defensins, cyclotides, and heveins-like antimicrobial peptides are common antimicrobial peptides that have been found to be involved in the defense system against fungi and insect pests. Based on their potential ability to protect crops from pests, bacteria, and pathogenic fungi, the use of antimicrobial peptide genes in creating transgenic plants has been largely conducted during the last decades, and these studies have obtained positive results against the growth of fungi and bacteria. This review will focus on the latest progress in studies of antimicrobial peptides related to biotic and abiotic stress tolerance in plants. We will also update the current progress in the development of antimicrobial peptide-based transgenic crops.

Oxidative stress (OS) is a condition in which there is an excess of reactive oxygen species (ROS) in the body, which can lead to cell and tissue damage. This occurs when there is an overproduction of ROS or when the body's antioxidant defense systems are overwhelmed. Quercetin is part of a group of compounds called flavonoids. It is found in high concentrations of vegetables, fruits, and other foods. Over the past decade, a growing number of studies have highlighted the therapeutic potential of flavonoids to modulate neuronal function and prevent age-related neurodegeneration. Therefore, quercetin has been shown to have antioxidant, anticancer, and anti-inflammatory properties, both in vitro and in vivo. Due to its antioxidant character, quercetin alleviates oxidative stress, thus improving cognitive function, reducing the risk of neurodegenerative diseases. On the other hand, quercetin can also help support the body's natural antioxidant defense systems, thus being a potentially practical supplement for managing oxidative stress. This review focuses on experimental studies supporting the neuroprotective effects of quercetin in Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD) and epilepsy.

Background: COVID-19 was initially identified as a respiratory system disorder, but it has been discovered to interact with and influence the cardiovascular system. COVID-19-associated cardiovascular (CV) complications are common, resulting in high acute phase mortality and a large number of morbidities in the chronic phase, thus severely impacting patients' quality of life and health outcomes. Nevertheless, clinical, cellular, and molecular biological factors underlying the pathophysiology of cardiovascular complications associated with COVID-19 are poorly understood. Objective: This review investigates putative underlying clinical factors as well as cellular and molecular biological mechanisms by which COVID-19 leads to acute CV complications, including state-of-the-art genomic sequencing-based findings, assessing the long-term CV consequences of COVID-19, and aiming to shed light on developing strategies for differential diagnosis, risk prognostic stratification, prevention, and clinical management of CV sequlea in COVID-19 patients. Methods: For this purpose, a through review of literature and published data was carried out from first report of COVID-19 till October 2023 to find out a comprehensive account of clinical, cellular and molecular genetic factors underlying COVID-19-associated cardiovascular diseases. Results: We found that the relationship between COVID-19 and CV risk is complex and multifaceted. In addition to acute COVID-19 detertriuos effects, COVID-19 survivors may experience long-term CV effects. We provide a detailed account of the involvement of a large number of genomic alterations, microRNAs, and novel viral as well as host proteins in CVDs associated with COVID-19, which has helped identify some novel drug targets to treat COVID-19-related cardiovascular complications. Conclusions: The relationship between COVID-19 and CV risk is complex and multifaceted. While COVID-19 primarily affects the respiratory system, it can also significantly affect CV health. as compared to classical cardiovascular diseases, there are new clinical, cellular and molecular biological factors in CVDs related to COVID-19, that need specific diagnostic assays, prognostic stratification and treatment modules. Therefore, specail care is must taken to treat cardiovascular diseases associated with COVID-19.

Thalassemia is one of the most prevalent genetic disorders worldwide which has been previously found to have an association with several physiological and organ complications. Several studies found both its positive and inverse correlation with glomerular filtration rate (GFR). Therefore, in this meta-analysis, we tried to assess the accurate correlation of thalassemia with GFR. We searched in Google Scholar, PubMed, and ScienceDirect, and from the initial 96 articles we finally could include 15 studies. The quality and publication bias assessment confirmed that all the studies were of high to moderate quality with no publication bias. The main outcome of the mean difference (MD) was -6.45, 95%CI: -18.50, 5.60 (P<0.00001), which indicated a negative correlation of GFR with thalassemia. The sensitivity analyses found one study as a slight outlier and reanalyzing the data excluding that study MD was achieved as -13.90, 95%CI: -24.22, -3.59 (P<0.00001) which even strongly supports our main outcome. Our result determined that the GFR is generally higher in healthy people as compared to thalassemia patients.

Increasing clinical and preclinical evidences implicate gut microbiome (GM) dysbiosis as a key susceptibility factor for neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s diseases (PD). In recent years, neurodegenerative diseases have not been viewed as driven solely by defects in brain, and the role of GM in modulating the central nervous system function via gut-brain axis has attracted considerable interest. Encouraged by GM researches, the next-generation probiotics may lead to tangible impacts on the treatment of neurodegenerative disorders. This review summarizes the current understandings of GM composition and characteristics associated with neurodegenerative diseases, and the demonstrations of molecules from GM affecting neurodegeneration. Particularly, applications of next-generation probiotics such as Clostridium butyricum, Akkermansia muciniphila, Faecalibacterium prausnitzii, and Bacteroides fragilis for remediation of neurodegenerative diseases are discussed.

Foliar fungal diseases in tomatoes include early blight (Alternaria linariae), Septoria leaf spot (Septoria lycopersici), and late blight (Phytophthora infestans) which is oomycetes. These are one of the significant production constraints in tomatoes. We describe the etiology, host range, distribution, symptoms, and disease cycle to understand the biology followed by management practices emphasizing the resistance breeding approach for these diseases. In crop improvement efforts, we provide an analytical review, including conventional and molecular methods for improving this disease resistance. Modern breeding tools, including genomics, genetic transformation, and genome editing, can be used to improve these traits. There is a good possibility of using these tools in the future to improve these traits.

Systemic autoimmune diseases (SAIDs) such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA) are fully related to the unregulated innate and adaptive immune systems involved in their pathogenesis. They have similar pathogenic characteristics including the interferon signature, loss of tolerance to self-nuclear antigens, and enhanced tissue damage like necrosis and fibrosis. Glucocorticoids and immunosuppressants, which have limited specificity and are prone to tolerance, are used as the first-line therapy. A plethora of novel immunotherapies have been developed including monoclonal and bispecific antibodies, and other biological agents to target cellular and soluble factors involved in disease pathogenesis such as B cells, co-stimulatory molecules, cytokines or their receptors, and signalling molecules. Many of these have shown encouraging results in clinical trials. CAR-T cell therapy is considered the most promising technique for curing autoimmune diseases, with recent successes in the treatment of SLE and SSc.

Delivery of drugs through the nasal route provides an alternative, yet highly efficacious modality for administering both large and small pharmaceutic molecules. This method proves particularly advantageous for drugs that are unstable during oral administration, as they undergo significant degradation in the gastrointestinal tract or metabolization through the first-pass effect in the liver. Nasal administration stands as a viable alternative to parenteral therapy and is also suitable for long-term medical management. The nasal mucosa, characterized by high vascularity and permeability, facilitates rapid pharmaceutical absorption, ensuring a swift onset of therapeutic action. Despite its noninvasive nature, the nasal delivery technique finds broad applicability for both local treatment and systemic therapy, as the drug directly enters systemic circulation. This article explores the feasibility of a novel spray delivery mechanism for intranasal drug deposition. The study aims to determine whether users can correctly follow the state-of-the-art application instructions for a nasal spray with an optimal nozzle placement angle (namely, 12-15°) at the nostril while maintaining sufficient safety and efficacy, and without engaging in preventable usage errors that could harm the user. Additionally, the study evaluates the effectiveness of device labeling, instructions for use, and a short video in supporting the correct application of the nasal spray at the optimal angle (12-15°) and assesses whether users can differentiate the product from others with similar appearances. We have also performed physical spray tests to experimentally evaluate drug penetration to the nasopharynx (a key target site for viral infections) for two different nozzle placements – one for current package instructions coming with over-the-counter spray products and the other for the optimal spray usage procedure to enhance targeted drug delivery. Human Factors (HF) validation studies were also conducted, instructing users to follow the application instructions of the nasal spray bottle with the nozzle placed at the optimal angle to target the nasopharynx. The experimental tests consistently confirmed improved penetration with the 12-15° nozzle placement, with visual cues proving effective when used in tandem with written instructions for guiding the study participants to adhere to the recommended usage procedures.

The increased cultivation of high THC-containing Cannabis sativa L. (cannabis), particularly in greenhouses, has resulted in a greater incidence of diseases and molds that can negatively affect the growth and quality of the crop. Among them, the most important diseases are root rots (Fusarium and Pythium spp.), Botrytis bud rot (Botrytis cinerea), powdery mildew (Golovinomyces ambrosiae), cannabis stunt disease (caused by Hop latent viroid), and a range of microbes that reduce post-harvest quality. An integrated management approach to reduce the impact of these diseases/microbes requires combining different approaches that target the reproduction, spread and survival of the associated pathogens, many of which can occur on the same plant simultaneously. These approaches will be discussed in the context of developing an integrated plan to manage the important pathogens of greenhouse-grown cannabis at different stages of plant development. These stages include maintenance of stock plants, propagation through cuttings, vegetative growth of plants, and flowering. The cultivation of cannabis genotypes with tolerance or resistance to various pathogens is a very important approach, followed by the maintenance of pathogen-free stock plants. When combined with cultural approaches (sanitation, management of irrigation, and monitoring for diseases) and environmental approaches (greenhouse climate modification), a significant reduction in pathogen development and spread can be achieved. The use of preventive applications of microbial biological control agents and reduced risk biorational products can also reduce disease development at all stages of production in jurisdictions where they are registered for use. The combined use of promising strategies for integrated disease management on cannabis plants during greenhouse production will be reviewed. Future areas for research are identified.

Parasitic diseases are among the most serious public health problems in developing countries, causing high mortality and economic burdens. The Trypanosomatidae family includes Leishmania spp. and Trypanosoma cruzi, which cause leishmaniasis and Chagas disease, respectively. Both these parasites are among the major agents of neglected tropical diseases (NTDs). Leishmaniasis is currently the second most widespread vector-borne parasitic disease after malaria. The World Health Organization (WHO) records approximately 0.7-1 million newly diagnosed leishmaniasis cases each year, resulting in approximately 20,000-30,000 deaths. Also, 25 million people worldwide are at risk of Chagas disease and an estimated 6 million people are infected with Trypanosoma cruzi. Despite the similarity of the parasites, the evolution of the disease and the clinical indexes are explicitly different in African, Asian, and American forms of infection. Clinical therapies are associated with drug resistance and side effects. As a result, the discovery of novel therapeutic agents has emerged as a top priority and a promising alternative. Peptide-based drugs are an attractive class of therapeutic agents. They are recognized for being highly selective and effective, as well as safe and well tolerated. Moreover, they are now being explored in the development of novel therapeutics for a variety of health disorders, including oncology, endocrinology, metabolic, cardiovascular, and bone diseases. In addition, they are being explored in tropical diseases such as leishmaniasis and Chagas disease. We will discuss current knowledge regarding the parasite life cycle, signs and symptoms, diagnosis, and treatment options for leishmaniasis and Chagas disease.

(1) Background: Bats are reservoirs and vectors of significant zoonotic diseases. Our study focuses on understanding the role of bats as reservoirs and carriers of coronaviruses, given their epidemiological significance and the recent global health crises stemming from coronavirus outbreaks. (2) Methods: We conducted virological screening of bats hibernating in military bunkers at the Natura 2000 site "Nietoperek" in Western Poland. This involved collecting and analyzing oral and anal swab samples from 138 bats across six species, using a combination of pan-coronavirus and SARS-CoV-2 specific PCR assays. (3) Results: Out of 138 bats, only one anal swab tested positive for coronavirus. However, we were not able to obtain genomic sequence from the sample. No SARS-CoV-2 was detected in any of the samples. The low prevalence of coronavirus in the studied colony contrasts with higher rates found in other regions and may be influenced by the physiological and behavioral conditions of bats during hibernation. (4) Conclusions: Hibernating bats may show a low prevalence of coronavirus, potentially due to the hibernation process itself. This finding indicates that hibernating bats may not be the most optimal subjects for screening zoonotic pathogens. However, continuous monitoring of bat populations for emerging and reemerging diseases is recommended for a comprehensive epidemiological understanding.

During the last decades, a growing number of studies have shown that infections during pregnancy have an important impact on both pregnant women and their fetuses. Our goal was to identify newborns from pregnancies with SARS-CoV-2 infection and to investigate the extension of neonatal complications using cardiac, abdominal and cerebral ultrasonography, hearing testing and indirect ophthalmoscopy. By contrast, neonates whose mothers were vaccinated against COVID-19 during pregnancy and those from pathology-free pregnancies have been examined. A total of 458 newborns were included, over a period of 10 months, divided into 3 groups, COVID-19 group, vaccine group and control group. Although 6 cardiac malformations were found in the COVID-19 group, no correlation was made compared to the vaccine and control group (p=0.07). Grade 1 intraventricular hemorrhage and hypoxic ischemic encephalopathy were the most prevalent among neonates from mothers with SARS-CoV-2 infection (p=0.002 and p&lt;0.001, respectively). The kidney anomaly found to be most frequent in this group was grade 1 unilateral hydronephrosis (p&lt;0.001). COVID-19 disease during the gestational period had no effect on the auditory or visual function. Despite the fact that our observations are relevant, further studies investigating the effects of SARS-CoV-2 infection during pregnancy and the neonatal outcomes are necessary.

Endocytosis in mammalian cells is a fundamental cellular machinery that regulates vital physiological processes, such as the absorption of metabolites, release of neurotransmitters, hormonal secretion, cellular defense, and delivery of biomolecules across the plasma membrane. A remarkable characteristic of the endocytic machinery is the sequential assembly of the complex proteins at the plasma membrane followed by transportation of various cargo molecules to different cellular compartments. In all eukaryotic cells, functional characterization of endocytic pathways is based on dynamics of the protein complex modules. To coordinate the assembly and functions of the numerous parts of the endocytic machinery, the endocytic proteins interact significantly within and between the modules. Clathrin dependent and independent endocytosis, caveolar pathway and receptor mediated endocytosis have been attributed in a greater variety of physiological and pathophysiological roles such as, autophagy, metabolism, cell division, apoptosis, cellular defense, and intestinal permeabilization. Notably, any defect or alteration in the endocytic machinery results in the development of pathological consequences associated with human diseases such as cancer, cardiovascular diseases, neurological diseases, and inflammatory diseases. In this review, an in-depth endeavor has made to illustrate the process of endocytosis, and associated mechanisms describing pathological manifestation associated with dysregulated endocytosis machinery.

The multitarget therapeutic strategy, as opposed to the more traditional ‘one disease-one tar-get-one drug’, may hold promise in treating multifactorial neurodegenerative syndromes, such as Alzheimer’s disease (AD) and related dementias. Recently, combining a photopharmacology approach with the multitarget-directed ligand (MTDL) design strategy, we disclosed a novel donepezil-like compound, namely 2-(4-((diethylamino)methyl)benzylidene)-5-methoxy- 2,3-dihydro-1H-inden-1-one (1a), which in the E diastereomeric form (and about tenfold less in the UV-B photo-induced isomer Z) showed the best activity as dual inhibitor of the AD-related targets acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). Herein, we investigated further photoisomerizable 2-benzylideneindan-1-one analogs 1b-h with the unconjugated tertiary amino moiety bearing alkyls of different bulkiness and lipophilicity. For each compound the thermal stable E diastereoisomer, along with the E/Z mixture as produced by UV-B light irradia-tion in the photostationary state (PSS, 75% Z), was investigated for the inhibition of human ChEs and MAOs. The pure E-diastereoisomer of the N-benzyl(ethyl)amino analog 1h achieved low nanomolar AChE and high nanomolar MAO-B inhibition potencies (IC50s 39 and 355 nM, re-spectively), whereas photoisomerization to the Z isomer (75% Z in the PSS mixture) resulted in a decrease (about 30%) of AChE inhibitory potency, and not in the MAO-B one. Molecular docking studies were performed to rationalize the different E/Z diastereoselectivity of 1h toward the two target enzymes.

The spectrum, intensity and overlap of symptoms between FGIDs and other gastrointestinal disorders characterize patients with FIGDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis and treatment's applicability is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found causing the continuous existence of low-inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and intestinal functions, including the involvement of the gut bacteria. In this review paper, we intend to promote a hypothesis that FGIDs, should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic and microbiome pathways. Hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, being omnipresent in chronic health conditions. Better understanding of inflammation role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs, may reduce patient heterogeneity and help clarify pathophysiology for better treatment.

Acute myocardial infarction (AMI), which is characterized by severe and fatal arrhythmias resultant from cardiac ischemia/reperfusion (CIR), is the leading cause of morbidity and mortality in the world. Considering that epiisopiloturin (EPI), an imidazole alkaloid found in the leaves of Pilocarpus microphyllus produded anti-inflammatory and antioxidant effects in an animal model of peritonitis, paw edema and peritonitis in mice, we decided to investigate the potential cardioprotective activity of EPI in animal model of CIR. Then, adult rats submitted to CIR pretreated with EPI 10 mg/kg (EPI10+CIR group) or 15 mg/kg (EPI15+CIR group) were compared to control animals submitted to CIR treated with saline solution 0.9% (CIR group). To evaluate the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) induced by CIR in these rats, the ECG analysis was performed. Serum levels of cardiac damage markers, total creatine kinase (CK) and CK-MB, were measured. The results showed that the AVB incidence was reduced from 80% to 30%, and LET incidence was reduced from 70% to 20%, compared to CIR group. Serum levels of LDH, total CK and, CK-MB was similar in all groups studied. These results indicate that the treatment with EPI (15 mg/kg, IV) before CIR was effective to produce cardioprotective effects. Thus, the use of EPI could be a promisse strategy to reduce the incidence of severe and fatal arrhythmias associated with AMI.

We hypothesized that reticuloruminal temperature and pH, as well as cow activity, can be used as biomarkers for the early diagnosis of clinical mastitis in dairy cows. Therefore, we aimed to detect the relationship between reticuloruminal temperature and pH, cow activity, and clinical mastitis in dairy cows. We randomly selected cows with clinical mastitis and clinical healthy cows (HG) out of 600 milking cows. We recorded the following parameters during the experiment: reticulorumen tem-perature (RR temp.), reticulorumen pH (RR pH), and cow activity. We used smaXtec boluses (smaXtec animal care technology®, Graz, Austria). In this investigation, reticulorumen data ob-tained seven days before diagnosis were compared to HG data from the same time period. CM cows were observed on the same days as the healthy cows. The healthy group’s RR pH was 7.32% higher than that of cows with CM. Reticulorumen temperature was also 1.25% higher in the CM group than in the control group. The healthy group had a higher average value for walking activity and was 17.37% higher than the CM group. The data of reticulorumen pH changes during 24 h showed that during the day, the pH changed from 5.53 to 5.83 in the CM group. By contrast, pH changed from 6.05 to 6.31 in the control group. The lowest reticulorumen pH in the CM group was detected on the third day before diagnosis. It was 15.76% lower than the highest reticulorumen pH detected on the sixth day before diagnosis. The lowest reticulorumen pH in CM cows was detected at 0 and 1 days before diagnosis. It was 1.45% lower than the highest reticulorumen pH detected on the second day before diagnosis. The lowest walking activity in the CM group was detected 0 days before diagnosis, 50.60% lower than on the fifth day before diagnosis. The lowest walking activity was detected 0 days before diagnosis, 39.57% lower than on the seventh day before diagnosis. In this study, we found that reticuloruminal temperature, reticuloruminal pH, and cow ac-tivity could be used as biomarkers for the early diagnosis of clinical mastitis in dairy cows.

The brain being arguably the most complex organ in the human body, its detailed functioning is yet to be fully deciphered, let alone accurately modeled. Nonetheless, the medical community has gathered quite a remarkable amount of studies about the consequences of illnesses and injuries on its development and functioning. This bibliographic review aims to cover mostly the findings related to the changes in the physical distribution of neurons and their connections - the connectome -, both structural and functional, as well as their modelling. It does not intend to offer an extensive medical description of all injuries and diseases affecting the brain, rather presenting the most common ones succinctly so the need for accurate brain modelling can be fully understood and pondered, offering propositions to this aim.

Neurodegenerative diseases encompass a broad spectrum of profoundly disabling disorders that impact millions of individuals globally. While their underlying causes and pathophysiol-ogy display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, constitutes a shared characteristic among them. Con-sequently, targeting the BBB has emerged as an innovative therapeutic strategy for address-ing neurological diseases. Within this review, we not only explore the neuroprotective, neu-rotrophic, and immunomodulatory benefits of mesenchymal stem cells (MSCs) in combating neurodegeneration but also delve into their recent role in modulating the BBB. We will delve into the cellular and molecular mechanisms through which MSC treatment impacts primary age-related neurological disorders like Alzheimer’s disease, Parkinson’s disease, and stroke as well as immune-mediated conditions such as multiple sclerosis. Our focus will center on how MSCs participate in the modulation of cell transporters, matrix remodeling, stabilization of cell-junction components, and restoration of BBB network integrity in these pathological con-texts.

Background Community health workers (CHWs) drawn from the general population are an important human resource in health care systems, preventing non-communicable diseases (NCDs) and contributing to an increase in healthy life expectancy in Japan. Thus, we have developed the COmmunity health workers perceptual and behavioral Competency Scale for preventing Non-communicable diseases (COCS-N) to measure CHWs’ competence in preventing NCDs. The purpose of this study is to examine individual and community factors affecting CHWs’ COCS-N scores. Methods Municipal public health nurses and other public health professionals are responsible for training and supporting CHWs in Japan. Therefore, the existence of CHWs and their willingness to participate in the study were confirmed with the municipalities, who were asked to distribute the self-administered questionnaire to CHWs where consent was obtained (N = 6,480). Variables used included demographic characteristics, COCS-N scores, and individual- and community-related factors. Logistic regression analysis was used to assess associations between variables. Results A total of 3,120 people completed the questionnaire, a valid response rate of 48.1%. The respondents’ mean age was 67.0 years (standard deviation = 9.0), and 88.0% were female. Comparison of the high- and low- competence groups in terms of NCD prevention based on COCS-N scores identified 13 factors associated with significant differences, including years spent working as a CHW (p < 0.001), subjective sense of health (p = 0.005), European Health Literacy Survey Questionnaire (HLS-EU-Q47) scores (p < 0.001), and community commitment scale (CCS) scores (p < 0.001). Logistic regression analysis revealed that HLS-EU-Q47 scores (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02–1.03) were a significant individual factor, while CCS scores (OR: 1.14, 95% CI: 1.11–1.16) were a significant community factor. Conclusions We found that the COCS-N score was associated with the individual factors overall health literacy (HL), perceptions of HL, and subjective sense of health, and with the community factor CCS scores. These results suggest that strengthening individual factors such as HL and subjective sense of health, and community factors such as sense of community is an effective strategy for increasing CHWs’ competence in preventing NCDs.

While it is well known that 98-99% of the human genome do not encode proteins, but are nevertheless transcriptionally active and give rise to a broad spectrum of noncoding RNAs (ncRNAs) with complex regulatory and structural functions, specific functions have so far been assigned to only a tiny fraction of all known transcripts. On the other hand, the striking observation of an overwhelmingly growing fraction of ncRNAs, in contrast to an only modest increase in the number of protein-coding genes, during evolution from simple organisms to humans, strongly suggests critical but so far essentially unexplored roles of the noncoding genome for human health and disease pathogenesis. Research into the vast realm of the noncoding genome during the past decades thus lead to a profoundly enhanced appreciation of the multi-level complexity of the human genome. Here, we address a few of the many huge remaining knowledge gaps and consider some newly emerging questions and concepts of research. We attempt to provide an up-to-date assessment of recent insights obtained by molecular and cell biological methods, and by the application of systems biology approaches. Specifically, we discuss current data regarding two questions: (1) By which mechanisms could evolutionary recent ncRNAs with critical regulatory functions in a broad spectrum of cell types (neural, immune, cardiovascular) constitute novel thera-peutic targets in human diseases ? (2) Since noncoding genome evolution is causally linked to brain evolution, and given the pro-found interactions between brain and immune system, could human-specific brain-expressed ncRNAs play a direct or indirect (immune-mediated) role in human diseases? Synergistic with the remarkable recent progress regarding delivery, efficacy, and safety of nu-cleic acid-based therapies, the ongoing large-scale exploration of the noncoding genome for human-specific therapeutic targets is encouraging to proceed with the development and clinical evaluation of novel therapeutic pathways suggested by these research fields.

Background: Glycogen storage diseases (GSDs), known as glycogenoses, belong to inborn metabolic defects in the glycogen metabolism pathway. Several types of GSDs are distinguished, including Ia, Ib, III, VI, and IX. GSDs manifest as excessive glycogen deposition in the liver and muscles, resulting in the dysfunction of these organs. Therefore, the treatment of choice is multitherapy that, due to dietary restrictions, may lead to nutritional deficiencies and organ complications. This study aims to assess anthropometric, body composition, skeletal status, results of selected laboratory tests, dietary, lifestyle and physical capacity analyses in patients with glycogenoses and compare the results between GSD I and GSD III-VI-IX groups. Results: The results indicate that GSD patients were overweight or obese (44% of patients had BMI +1SD or +2SD) with high percentage of fat tissue (50% of patients had above 30% of body fat) and inadequate bone mineralisation (total body less head: median z-score -0.9, L2-L4 segment: median z-score -1.65). GSD I patients had the highest risk of developing obesity (67% of them had above 30% of body fat) and osteoporosis (total body less head: median z-score -1.0, L2-L4 segment: median -1.7). Conclusions: Special attention should be paid to appropriate diet and supplementation in patients with glycogenoses.

The pathophysiology of many mood disorders is closely related with abnormal stress response associated with the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol overproduction. The hippocampus, key structure of the limbic system responsible for both cognitive and emotional spheres, is selectively vulnerable to excess of glucocorticoids (GCs) inducing neuroinflammation and neurodegeneration. The antiGC therapy of psychiatric diseases, in particular depressive disorders, may be a useful additional treatment. Among other approaches, targeting glucocorticoid receptors, abounded in the hippocampus, is regarded as highly promising. However, though the preclinical data provide firm evidence to the concept of antiGC therapy for stress-related diseases, clinical studies still are at the proof-of-concept stage. Noteworthy, chronic GC excess is associated not only with mood diseases, but also with cognitive decline, metabolic disorders, diabetes. Potentially, antiGC (HPA axis modifying) therapy may alleviate affective symptoms, cognitive disturbances, GC and insulin resistance and adverse side effects of conventional drugs through beneficial effects on hippocampal dysfunction and neurodegeneration, neuroinflammation, and neurogenesis. Since stress/GC-associated neuroinflammation-mediated pathology of the limbic system and, specifically, the hippocampus, is a general feature typical for many brain diseases, the concept of antiGC therapy may be extended, tested and validated in a wider spectrum of cerebral pathologies.

Commonly the periodontitis has been linked to periodontopathogens categorized in Socransky's microbial complexes, however, there is a lack of knowledge regarding “other microorganisms” or "cryptic microorganisms", which are rarely thought of as significant oral pathogens and are neither previously categorized nor connected to illnesses in the oral cavity. This study hypothesized that these cryptic microorganisms could contribute to the modulation of oral microbiota present in health or disease (periodontitis and/or OSA patients). For this purpose, the presence and the correlation among these cultivable cryptic oral microorganisms were identified and their possible role in both conditions was determined. Data from oral samples of individuals with or without periodontitis and with or without OSA were obtained from a previous study. Demographic data, clinical oral characteristics, and genera and species of cultivable cryptic oral microorganisms identified by MALDI-TOF were recorded. The data of 75 participants were analyzed to determine the relative frequencies of cultivable cryptic microorganisms’ genus and species, microbial clusters and correlations tests were performed. According to periodontal condition, Gingivitis - dental biofilm-induced in reduced periodontium and stage III periodontitis were found to have the highest diversity of cryptic microorganism species. Based on the experimental condition these findings showed that there are genera related to disease conditions and others related to healthy conditions, with species that could be related to different chronic diseases being highlighted as comorbidities periodontitis and OSA. The cryptic microorganisms within the oral microbiota of patients with periodontitis and OSA are present as potential pathogens, promoting the development of dysbiotic microbiota, and the occurrence of chronic diseases, which have been previously proposed to be common risk factors for periodontitis and OSA. Understanding the function of possible pathogens in the oral microbiota will take more research.

Alzheimer's disease (AD) remains a significant challenge in the field of neurodegenerative disor-ders, even nearly a century after its discovery, due to the elusive nature of its causes. The develop-ment of drugs that target multiple aspects of the disease has emerged as a promising strategy to address the complexities of AD and related conditions. The immune system's role, particularly in AD, has gained considerable interest, with nanobodies representing a new frontier in biomedical research. Advances in targeting antibodies against amyloid-β (Aβ) and using messenger RNA for genetic translation have revolutionized the production of antibodies and drug development, open-ing new possibilities for treatment. Despite these advancements, conventional treatments for AD, such as Cognex, Exelon, Razadyne, and Aricept, often have limited long-term effectiveness, under-scoring the need for innovative solutions. This necessity has led to the incorporating of advanced technologies like artificial intelligence and machine learning into the drug discovery process for neurodegenerative diseases. These technologies help identify therapeutic targets and optimize lead compounds, offering a more effective approach to addressing the challenges of AD and similar conditions.

Data on immunogenicity, immune response persistency, and safety of COVID-19 boosters in patients with comorbidities are limited. Therefore, we aimed to evaluate and compare three different boosters in individuals who received two doses of the BBIBP-CorV vaccine including underlying diseases and healthy cases as control. One hundred forty subjects including 63 ones with at least one of three underlying diseases (UD) (including obesity, hypertension, and diabetes mellitus) and 77 healthy ones (HC) who had received a booster dose (either PastoCovac Plus or PastoCovac or BBIBP-CorV) were enrolled. The presence of SARS-CoV-2 antibodies was assessed before the booster injection and 28, 60, 90, and 180 days after it. Moreover, the adverse events (AEs) were recorded on days 7 and 21 post-booster shot for evaluating safety outcomes. Significantly increased titers of anti-spike, anti-RBD, and neutralizing antibodies were observed in both UD and HC groups 28 days after the booster dose, although the titer rise of anti-spike IgG and anti-RBD IgG was insignificantly inferior in the UD group compared to the HC group. All antibodies’ titers declined, with no significant differences between the two groups over time. Notably, all specific antibodies persisted up to 180 days; particularly the neutralizing antibody in both groups. Furthermore, no significant difference in antibody levels was observed between each UD subgroup and the HC group, except for neutralizing antibodies in the hypertension sub-group. PastoCovac Plus and PastoCovac boosters induced higher antibodies’ fold rise in UD individuals than BBIBP-CorV booster recipients. Safety outcomes did not show any serious AEs after the booster injection. The overall incidence of AEs post the booster injection was higher in the UD group than the HC group. Furthermore, the highest systemic AEs rate was reported in the UD group receiving the BBIBP-CorV booster. In conclusion, administration of COVID-19 boosters can equally induce robust and persistent humoral immune responses in individuals with or without UD primarily vaccinated with 2-doses of the BBIBP-CorV. Protein-based boosters with higher antibodies' fold rise and lower AEs in individuals with comorbidities might be considered a better choice for these individuals.

The rhizosphere is a rich source of actinomycetes which can produce several potential biologically-active secondary metabolites. The principal goals for this research are to extract, purify and characterize the bioactive secondary metabolites produced by three different strains of actinomycetes isolated from the rhizosphere of rosemary, black locust and olive. The plant growth-promoting effect (PGPE) of the studied strains of actinomycetes on Ocimum basilicum L. (basil) and disease-control effect on necrotic stem lesions of “black leg” caused by Fusarium tabacinum on basil, were in silico evaluated. The cell-free culture filtrates from the studied actinomycetes isolates were evaluated in vitro for their antimicrobial activity against some common phytopathogens. The secondary metabolites obtained from the cell-free culture filtrates have been chemically characterized using high‐resolution electrospray ionization of liquid-chromatography/mass-spectrometric detection (ESI-(HR)Orbitrap-MS). Results of in silico trial showed that all studied isolates demonstrated PGPE on basil seedlings improving some Eco-physiological characteristics and reduced the disease incidence of F. tabacinum. The extracted metabolites from the studied actinomycetes demonstrated antimicrobial activity in Petri-plates assay. The chemical analysis revealed the presence of totally 20 different components. This research emphasizes how valuable the examined isolates are for producing bioactive compounds, indicating their putative antimicrobial activity and their potential employment as fungal-biocontrol agents. In particular, the obtained results revealed the possibility of green-synthesis of some important secondary metabolites such as N-Acetyl-L-histidinol, Rhizocticin A and Eponemycin from actinomycetes. The bioactive metabolites may be successively used to develop novel bio-formulations for both crop protection and/or PGPE.

The suitability of an animal model to study human diseases heavily relies on the similarity between the two species at the genetic, epigenetic, gene expression and metabolic levels. However, consistent data from different animal models at each level to evaluate this suitability is lacking. With the availability of genome sequences for many mammalian species it is now possible to compare animal models based on the genomic similarities. Here, we compare the coding sequences (CDS) of five mammalian models that include rhesus macaque, marmoset, pig, mouse and rat with those from human. We identified 10,316 conserved CDS across the five organisms and human based on the sequence similarity. Mapping the human disease-associated single nucleotide polymorphisms (SNPs) from these conserved CDS in each species has identified species-specific association with various human diseases. While associations for a disease such as colon cancer were prevalent in multiple model species, pig showed the highest number (117 diseases) of model-specific human disease associations. Based on the percentage of disease-associated SNP-containing genes, marmoset models are well suited to study many human ailments including behavioral and gastrointestinal diseases. Comparison of gene expression levels of the conserved CDS from colon, heart, kidney, lung, skeletal muscle, and spleen tissues in these models showed correlations with human expression levels in a tissue-specific manner. In the gastrointestinal tissues (colon, spleen), the pig showed the highest correlation while mouse displayed a better correlation in the heart and kidney. This study demonstrated genomic as well as tissue-specific expression-based similarity evaluation of five animal models against human that could help investigators select a suitable animal model to study their targeted disease.

Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins and decrease levels of toxic proteins. ASOs are being developed for the treatment of several diseases, including motor neuron diseases (MNDs), a group of neurodegenerative disorders characterised by the loss of motor neurons, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MND, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here we report that among eighteen representatives of the multifunctional S100 protein family only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent Kd values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1-0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatic analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect efficacy of anti-TNF treatment in various diseases.

The new class of mRNA vaccines is studied extensively, leading to many novel prospects based on the pivotal success of vaccines against the SARS-Cov-2 virus. Many novel mechanisms of immune response discovered have led to the possibility of mutation-resistant vaccines by combining multiple conserved epitopes as antigens to manipulate the T-cell and B-cell responses; these antigens can also come from different organisms, providing protection against numerous diseases and of most tremendous significance is the utility of mRNA vaccines in preventing and treating more than 100 autoimmune disorders. This is a significant humanitarian breakthrough given the ease and faster and low cost of mRNA vaccines, being a chemical entity. This paper provides a prospective analysis of mRNA vaccines with much broader applications than anticipated when these vaccines entered treating SARS-Cov-2 infections.

The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. It implies the extraction and analysis of non-solid biological tissues (serum, plasma, saliva, urine and cerebrospinal fluid) without undergoing invasive procedures to determine disease prognosis. Liquid biopsy can be used for the screening of several components such as extracellular vesicles, microRNAs, cell-free DNA, cell-free mitochondrial and nuclear DNA, circulating tumor cells, circulating tumor DNA, transfer RNA and circular DNA or RNA derived from body fluids. Its application includes early disease diagnosis, surveillance of disease activity, and treatment response monitoring, with growing evidence for validating this methodology in cancer, liver disease, and central nervous system (CNS) disorders. This review will provide an overview of mentioned liquid biopsy components, which could serve as valuable biomarkers for the evaluation of complex neurological conditions, including Alzheimer’s disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, traumatic brain injury, CNS tumors, and neuroinfectious diseases. Furthermore, this review highlights the future directions and potential limitations associated with liquid biopsy.

Nutraceuticals comprise dietary supplements, functional foods, medicinal foods, and pharmaceuticals. However, to date all these concepts are interpreted in different ways with the rapid increasing knowledge on nutrition, medicine, and plant biotechnology changing the concepts about food, health and agriculture. What matters are the bioactive elements conveyed by foodstuffs as nutrients or non-nutrients, which interfere with human metabolism and have impact on health, aging and well-being. Food, not nutrients, is the fundamental unit in nutrition and edible mushrooms, are fungi that supply unique biological compounds, different from plant or animal origin, which significantly impact on health status. Their influence on medicinal interventions has been known and studied for many years. The role on neurodegenerative disorders has been recently investigated and their significance on many other diseases has been well demonstrated. On this note it is synthesized the more recent knowledge of some edible mushrooms and preparations on Ménière’s disease, a lifelong condition it can develop at any age, but most commonly appearing between 40 and 60 years of age.

Climate change presents an urgent and impending threat to virtually all global biological systems. In recent years, there has been a surge in research endeavors aimed at investigating the potential relationship between changes in climate patterns and the spread of infectious diseases. This scoping review included studies on global warming and infectious diseases from 2019 to 2023, The studies included in this research were obtained from reputable academic databases such as Web of Science and google scholar. A systematic keyword search was conducted to identify relevant studies, and a predefined set of inclusion criteria was applied to review and select the appropriate studies for analysis. This review found that climate change has a remarkable impact on the dissemination and incidence of many infectious diseases, it increases microbial resistance and may increase the prevalence the arthropods-borne diseases with mild effect on fungal infections, also, the low to middle income countries may be affected more than other countries from these virulent pathogens, this study concluded that a future research in the field of climate change and infectious diseases should involve a thorough examination of the transmission of diseases, considering both direct and indirect modes of transmission

Given the remarkable progress in global health and overall quality of life, the significant rise in life expectancy has become intertwined with the surging occurrence of neurodegenerative disorders (ND). This emerging trend is poised to pose a substantial challenge to the fields of medicine and public health in the years ahead. In this context, Alzheimer's disease (AD) is regarded as a ND that causes recent memory loss, motor impairment and cognitive deficits. AD is the most common cause of dementia in the elderly and its development is linked to multifactorial interac-tions between the environment, genetics, aging and lifestyle. The pathological hallmarks in AD are the accumulation of beta amyloid (A) peptide, the hyperphosphorylation of tau protein, neuro-toxic events and impaired glucose metabolism. Due to pharmacological limitations and in view of the prevailing glycemic hypometabolism, the ketogenic diet (KD) emerges as a promising non-pharmacological possibility for managing AD, an approach that has already demonstrated efficacy in addressing other disorders, notably epilepsy. KD consists of a food regimen in which carbohydrate intake is discouraged at the expense of increased lipid consumption, inducing met-abolic ketosis, whereby the main source of energy becomes ketone bodies, instead of glucose. Thus, under these dietary conditions, neuronal death through lack of energy would be decreased, inasmuch as the metabolism of lipids is not impaired in AD. In this way, the clinical picture of patients with AD would potentially improve, through the slowing down of symptoms and delaying the progression of the disease. Hence, this review aims to explore the rationale behind utilizing the KD in AD treatment while emphasizing the metabolic interplay between KD and the improvement of AD indicators, drawing insights from both pre-clinical and clinical investigations.

Children five years or younger in low- and middle-income countries (LMICs) are severely affected by diarrhoea disease, especially in the sub-Saharan region. Hence, the study aimed at determining the prevalence and determinants of diarrhea disease among children under 5 years in Epworth Township, Zimbabwe. A descriptive cross-sectional study was conducted at a local clinic in Epworth Township, Harare. A convenience sampling strategy was used to recruit study participants for participation and 386 children were enrolled in the study. The majority were male children (n=229; 59.3%), while there were more female caregivers (n=370; 95.9%) than male caregivers (n=16; 4.1%). The prevalence of diarrhea disease in the study was 25.1%. The determinants associated with diarrhea were being partially vaccinated (OR 2.38, CI 95% 2.80–8.22), collecting water more than 1 kilometre from a household (OR 4.55; CI 95% 2.10–9.85) and using untreated water (OR 6.22; CI 95% 2.13–18.20). The age of the caregiver and using a clean water container (OR 0.05; p=0.020) were protective factors. Provision of primary health care, especially prevention of disease through immunization and rendering environmental health services could reduce the prevalence of diarrhea in disadvantaged townships.

One of the most important problems in the presence of epidemics and pandemics is an accurate prediction and preparedness. Scholars and experts argue that future pandemics and/or epidemics are almost inevitable events and is not whether next pandemics will happen, but when a new heath emergency will emerge. Epidemiologic models for prediction of Coronavirus Disease 2019 (COVID-19) have shown many limitations because of unpredictable dynamics of the new viral agent SARS-CoV-2 in environment and society. The main goals of this study are twofold: first, the analysis of anthropogenic activities and factors that may trigger pandemic threats; second, the planning of new directions for strategies to reduce risks that a pandemic threat emerges and/or in the initial phase to reduce vast diffusion and negative impact of new viral agents that can generate hazards and problems in public health, environment and socioeconomic systems. In particular, the investigation and understanding of sources and driving factors concerning the emergence and diffusion of new pandemics have critical aspects for strategic actions of forecast, prevention and preparation of effective policy responses to cope with next pandemic crises and health emergencies. Insights here endeavor, whenever possible, to clarify these problems to increase the knowledge of the sources and factor determining the emergence of new viral agents in order to design optimal response policies to face next pandemic diseases similar to COVID-19. .

This article reviews the introduction of Alzheimer's Disease (AD), neural networks, training and learning of neural networks, applications of neural networks in early diagnosis of AD, applications of neural networks in AD drug discovery, other brain diseases, and challenges faced by AD. First, the paper introduces the background and characteristics of AD. AD is a degenerative neurological disorder characterized by impaired memory, decreased cognitive function, and loss of neurons. These characteristics place a huge burden on the lives and families of patients. Next, the basic principle and structure of neural network are discussed. A neural network is a computational model made up of multiple neurons that can perform tasks by learning and adapting to input data. In particular, the key concepts of neural network hierarchy, activation function and weight adjustment are discussed. Then, the training and learning methods of neural networks are discussed. Common techniques such as backpropagation algorithm and gradient descent optimizer are introduced in detail, as well as the importance of data preprocessing and model evaluation. Next, the paper focuses on the application of neural network in early diagnosis of AD. By extracting features from brain image data, neural networks can automatically identify differences between AD patients and healthy subjects, enabling early diagnosis and intervention. In addition, the application of neural networks in AD drug discovery is also discussed. By analyzing and predicting a database of known drugs, neural networks can help discover potential treatments for AD and speed up the drug discovery process. The paper further explores the application of neural networks in other brain diseases and highlights the challenges faced by AD, such as the lack of reliable biomarkers, complex pathological mechanisms, etc. In summary, this paper presents a systematic overview of AD, neural networks, training and learning of neural networks, applications of neural networks in early diagnosis of AD and drug discovery, and other brain diseases and challenges associated with AD.

Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease, char-acterized by the progressive death of motor neurons, leading to paralysis and death. It is a rare disease distinguished by high patient-to-patient heterogeneity, making its study arduous and complex. Extracellular vesicles (EVs) emerged as an important player in ALS development. Thus, ALS phenotype-expressing cells can spread their abnormal bioactive cargos through the secretion of EVs, even at far distant tissues. Importantly, due to their nature and composition, EVs’ formation and cargo can be exploited for the better comprehension of this elusive disease and identification of novel biomarkers, as well as for potential therapeutic applications, such as those based on stem cell-derived exosomes. This review highlights the recent advances in the identification of the role of EVs in ALS etiopathology and how EVs can be promising new approaches for therapeutic strategies.

Cold atmospheric plasma (CAP) has emerged as a promising therapeutic technology, distinguished by its safety, efficiency, and minimal side effects. With increasing applications in dermatology, CAP demonstrates antimicrobial efficacy against bacteria, viruses, and fungi, supports tissue proliferation and wound healing, and hinders the growth and migration of tumor cells. This review encompasses the concept, physical characteristics, and current research applications of CAP in dermatology. CAP, a gas cloud produced by ionizing gases, operates at room temperature, ensuring safety and efficacy in dermatological use. Its effects are mediated through active components like reactive oxygen and nitrogen species (RONS) and ultraviolet radiation. The extensive research covered in this paper explores CAP's applications in skin infections, immune-related diseases, and tumor diseases. As a biologically suitable technology, cold atmospheric pressure plasma finds widespread use in medicine, including medical device sterilization, dentistry, oncology, and dermatology. The direct and indirect forms of CAP applications, including plasma-activated liquids, complement each other. CAP holds promise as a dermatological treatment technique, but further exploration and research are needed. This article briefly explores CAP's diverse applications and potential utility within dermatology. The objective is to enhance the progress of plasma medicine by furnishing a concise overview of the applications of this groundbreaking technology in dermatological contexts.

KV channel-interacting proteins (KChIPs) belong to a family of Ca2+-binding EF-hand proteins that are able to bind to the N-terminus of the KV4 channel α-subunits. As the auxiliary subunit, KChIPs are critically involved in regulating the amplitude and gating properties of KV4 channels by modulating their cell surface trafficking, voltage-dependent activation, inactivation kinetics, and recovery rate from inactivation. IKs, ICa,L, and INa can also be regulated by KChIPs. KChIPs are predominantly expressed in the brain and heart, where they contribute to the maintenance of the excitability of neurons and cardiomyocytes by modulating the KV4 currents. Interestingly, all KChIPs can act as transcription factors to control the expression of genes involved in pain, memory, and circadian regulation. Altered expression of KChIPs has been implicated in the pathogenesis of many diseases, such as arrhythmia, heart failure, Alzheimer's disease, etc. In this review, we summarize the research progress of KChIPs in their structural properties, physiological functions, and pathological roles in disease progression, and provide an overview of the therapeutic potential of KChIPs as pharmacological targets for associated disorders.

Dengue virus (DENV) is a member of the Flaviviridae family and is responsible for the most common mosquito-borne human disease. Currently, there are no available antiviral drugs to treat DENV infections. However, certain flavonoids, including baicalein and baicalin, have demon-strated significant anti-DENV effects in vitro. This study aimed to assess the bioavailability of baicalein and its metabolite, baicalin, in the blood serum of Albino Wistar rats using the LC/MS/MS method. The in vitro activity of sera obtained from rats administered baicalein was evaluated for its anti-DENV properties using quantitative RT-PCR and the Foci Forming Reduction Assay (FFRA). The results obtained through LC/MS/MS analysis indicated that the bioavailability of baicalin in rat blood serum reached 44.20 µg/ml one hour after oral administration of baicalein. Furthermore, the sera collected from rats given baicalein exhibited a significant 78.26% inhibition of DENV-2 replication when tested against Dengue-2 using both quantitative RT-PCR and FFRA. These findings suggest that baicalein and baicalin hold promise as potential therapeutic candidates for further investigation in the development of treatments against DENV infections.

Cardiovascular diseases (CVD) are chronic diseases associated with a high risk of mortality and morbidity. Early detection of CVD is crucial to initiating timely interventions, such as appro- priate counseling and medication, which can effectively manage the condition and improve patient outcomes. Preventive measures should be implemented at the general public level, promoting a healthy lifestyle, and at the individual level, that is, in people with moderate to high risk of CVD or patients already diagnosed with CVD by addressing an unhealthy lifestyle. Personalized early diagnostic systems based on artificial intelligence (AI), ontologies, and other medical information processing systems may prove to be a great preventive measure. In this paper, we focus on the use of ontology-inspired database models in the diagnosis of cardiovascular disease, as well as their potential for use in web application development.

Anthocyanins are among the best-known phenolic compounds and possess remarkable biological activities, including antioxidant, anti-inflammatory, anticancer, and antidiabetic effects. Despite their therapeutic benefits, they are not widely used as health-promoting agents due to their insta-bility, low absorption, and thus, low bioavailability and rapid metabolism in the human body. Recent research suggests that the application of nanotechnology could increase their solubility and/or bioavailability, and thus, their biological potential. Therefore, in this review, we decided to provide, for the first time, a comprehensive overview of in vitro and in vivo studies on nanocarriers used as delivery systems of anthocyanins, and their aglycones, i.e., anthocyanidins alone or com-bined with conventional drugs to the treatment or management of chronic diseases.

Kinases play an important role in regulating various intracellular signaling pathways that control cell proliferation, differentiation, survival and other cellular processes and their deregulation causes more than 400 diseases. Consequently, macrocyclization can be considered a noteworthy approach to develop new therapeutic agents for human diseases. Macrocyclization has emerged as an effective drug discovery strategy over the past decade to improve target selectivity and potency of small molecules. Small compounds with linear structures upon macrocyclization can lead to changes in their physicochemical and biological properties by firmly reducing conformational flexibility. A number of distinct protein kinases exhibit similar binding sites. Comparison of protein binding site provides crucial insights for the drug discovery and development. Binding site similarities are helpful to understand polypharmacology, identifying potential off-targets and repurposing of known drugs. In this review, we focused on comparing binding sites of those kinases for which macrocyclic inhibitors are available/studied so far. Furthermore, we calculated the volume of binding site pocket for each targeted kinase and then compared it with the binding site pocket of the kinase for which only acyclic inhibitors were designed till date. Our review and analysis of several explored kinases might be useful to target new protein kinases for macrocyclic drug discovery.

Background: Cardiovascular diseases (CVDs) are a rising global burden. Preventative strategies such as Cardiac Rehabilitation (CR) have shown a marked reduction of disease burden. Despite this, CR is underutilized worldwide. This study aims to identify the barriers to CR among patients diagnosed with CVD. Methods: A scoping review of the literature was conducted following the Joanna Briggs Institute (JBI) guidelines. Three major databases including CINAHL, PubMed, EBSCOhost and Scopus were used to obtain studies published between 2010 and 2023. Search terms such as “Cardiac rehab*”, “Barrier*”, “Cardiovascular”, “Disease” And “diagnosis*” Were utilized in order to obtain subject-specific studies relevant to the research question. Results: From the initial 2098 studies only 14 were included in the final analysis, consisting of both qualitative and quantitative designs. The thematic analysis included “healthcare system-related factors”, “Socioeconomic factors”, and “individual characteristics”. Healthcare system-related factors were mostly related to poor availability of CR programs, lack of proper referral strategies, inadequate knowledge of CR provider and inter-provider communication issues, and lack of alternative methods of CR delivery. Socioeconomic barriers were lack of education, longer distance to CR facilities, high cost of care, unemployment, and poor income status. Identified individual characteristics were female gender, older age, and comorbidities. Conclusion: Lack of resources, poor access, educational attainment, and high cost of care were some of the barriers to CR, particularly in low and middle-income countries (LMICs). Health policymakers and healthcare providers should implement strategies incorporating issues identified in this scoping review. Systematic reviews may be required to confirm these findings.

Egypt faces numerous challenges in achieving food and nutritional security, due largely to its unique geography, water stress, and population growth. However, nontraditional crops and pseudo cereals such as buckwheat, quinoa, sorghum, teff, and millet offer promising avenues for sustainable agricultural development and improved nutrition. These crops exhibit high tolerance to adverse environmental conditions such as soil salinity and drought and are rich in essential nutrients like protein, amino acids, and vitamins. They also present an economic advantage due to their short growing seasons and adaptability to marginal lands. Recent advancements in remote sensing and Geographic Information Systems (GIS) technology, along with crop simulation models, provide further opportunities for optimizing land and water resources for these nontraditional crops. Their exceptional nutritional values, including low glycemic indices and gluten-free properties, make them well-suited to address current health challenges, such as malnutrition and the increasing prevalence of non-communicable diseases. The study emphasizes the need for further research to investigate land suitability, water management, and economic viability for the cultivation and commercialization of these crops. By leveraging these opportunities, Egypt has the potential to not only close its food gap but also improve overall nutritional well-being, contributing to both food security and sustainable agriculture.