Abstract: Defective CFTR (cystic fibrosis transmembrane conductance regulator) is pathognomonic for cystic fibrosis (CF), which is characterized by accumulation of tenacious secretions in pulmonary airways, as well as by abnormal ductal secretions in other organs, including pancreas and prostate. The advent of CFTR modulating therapies has markedly improved the clinical status and survival of CF patients, primarily attributable to improved lung function. Previous publications reported that decline in CFTR function was associated with decline in activity and expression of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB). ARSB removes 4-sulfate groups from N-acetylgalactosamine 4-sulfate residues and is required for the degradation of chondroitin 4-sulfate and dermatan sulfate, two sulfated glycosaminoglycans which accumulate in cystic fibrosis. Both declines in ARSB and in CFTR have been associated with development of malignancies, including prostate malignancy. The experiments in this report show that similar effects on invasiveness are present when either CFTR or ARSB is inhibited in human prostate epithelial cells, and these effects resemble findings detected in malignant prostate tissue. Effects of CFTR inhibition are reversed by treatment with recombinant human ARSB in prostate cells. These results suggest that treatment by rhARSB may benefit patients with cystic fibrosis and prostate cancer.

Abstract: The rise of antimicrobial resistance poses a significant challenge to global health, necessitating the exploration for novel antimicrobial agents. Eucalyptus species, widely used in traditional African medicine, have shown promise in this regard. This systematic review investigates the antimicrobial potential of Eucalyptus species used in Africa. A systematic search was conducted via PubMed, Scopus, and Embase for African studies investigating the antimicrobial potential of Eucalyptus using the query: "Eucalyptus" AND ("Antimicrobial" OR "Antibacterial") AND (list of African countries). A total of 585 studies were retrieved and exported to Mendeley Desktop for de-duplication. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, only African research on the antibacterial activity of eucalyptus were included in the selection of studies. The included studies covered nine (9) countries across various regions in Africa, and twenty (20) Eucalyptus species with the most frequently studied species being Eucalyptus globulus, Eucalyptus camaldulensis, and Eucalyptus torelliana. The Eucalyptus extracts were reported to exhibits good inhibitory actions against a wide range of microorganisms. The findings emphasize the importance of species selection and extraction methods in maximizing antimicrobial efficacy and calls for their exploitation as therapeutic agents in various biomedical applications.

Abstract: This study analyzes for the first time the genetic diversity, connectivity, and evolutionary dynamics of the small red scorpionfish (Scorpaena notata) in the Balearic Islands based on mitochondrial DNA. Nucleotide diversity of the Cytochrome c oxidase subunit I (COI) gene was found to be low compared to other commercial fish species, suggesting that fishing may be impacting the population despite being a by-catch species. In contrast, the Control Region (CR) showed higher genetic variability. Demographic history analyses suggest that S. notata underwent a population expansion during the Pleistocene, possibly driven by sea-level changes. Genetic structure analyses (Fst and AMOVA) indicated genetic homogeneity and high connectivity among the Balearic Islands’ population, likely facilitated by its passive dispersion with pelagic eggs and larvae and the oceanographic conditions of the region. Our results indicate that the entire Balearic Islands should be considered as a unique Management Unit, although its potential relation to other nearby areas, such as the Iberian Peninsula, should also be studied.

Abstract: The evaluation of external pelvimetry measurements and the genetic factors influencing them is essential for improving morphological characteristics and reproductive performance in cattle. This study investigates the relationship between single nucleotide polymorphisms (SNPs) and external pelvimetry measurements in Simmental cows, considering traits such as croup height (CH), buttock height (BH), croup width (CW), rump angle (RA) and croup length (CL). A total of 33 SNPs, located on multiple chromosomes, were identified near relevant genes such as CLSTN2, DPYD, FBXL7, FBXL13, SEMA6A, RUNX2, FSTL4, DST, DCBLD2, FRMD6, CAV2.3, ABL2, SH3BP4, RSBN1L, and SAMD12, suggesting that these genetic variants may influence the development and morphology of the pelvic bones. Statistical analysis revealed significant relationships between certain allele variants and croup measurements, highlighting that the presence of alternative alleles can modify their morphological traits.

Abstract: Bone morphogenetic protein 9 (BMP9) is a cytokine belonging to the transforming growth – beta (TGF-β) family mainly known for its role in regulating vascular function, specifically keeping blood vessels stable and preventing unwarranted growth. It has been previously demonstrated to be involved in hereditary hemorrhagic telangiectasia (HHT) and vascular remodeling acting via HHT target genes. Inhibitor of Differentiation/DNA – Binding 3 (ID3) has been known to be a significant mediator for stages of cell differentiation within the context of BMP9 signaling in HHT development; however, the roles of ID3 and its targets within the HHT pathways are still limited. This brief report highlights significant ID3 targeted - BMP9 gene signatures and networks that may play a key role in the modifications of HHT.

Abstract: Diseases are one of the main attributes of life. Failures in attempts to control these natural phenomena for all living things are due to the epistemological insufficiency of the natural philosophical paradigm. The author's goal is to familiarize specialists with the phylogenetically conditioned quantum nature of disease programs, which is manifested by their pathogenetic pattern. The author's task is to draw the attention of specialists to the possibility of access to the storage of these programs in the body to control them. The solution to this problem is possible only with the interdisciplinary collaboration of specialists capable of developing the appropriate technologies. This publication substantiates the possibilities for this.

Abstract: Nucleic acids are significant components of daily diet and have attracted attention regarding their metabolic and nutritional roles. Numerous studies have explored the biological functions of nucleotides, nucleosides, and functional nucleic acids like microRNAs. However, the nutritional value and metabolic mechanisms of RNA oligonucleotides derived from ribosomal RNA (rRNA)—a major form of nucleic acids in nature remain underexplored. Here, yeast was utilized as a model organism to investigate the absorption and metabolism of oligonucleotides obtained from rRNA. We cultured yeast directly using RNA oligonucleotides as one nutrient, demonstrating that yeast can efficiently utilize RNA oligonucleotides (length < 30 nt) as a nitrogen source. Through proteomic analysis to assess the expression levels of key proteins associated with transport and metabolic processes, we found that the key proteins involved in endocytosis, autophagy, and RNA degradation were upregulated. These results clearly demonstrate that yeast directly uptakes RNA oligonucleotides via endocytosis, which are subsequently degraded into nucleosides, ammonia and β-Alanine through autophagy and RNA degradation, thus providing substrates for synthesizing nucleic acid and other organic nitrogenous metabolites. Our findings and proposed mechanisms for RNA absorption and metabolism in eukaryotic cells can promote future research in both nutrition and nucleic acid metabolism.

Abstract: Background/Objectives: With the number of detected breast cancer cases growing every year, there is a need to augment histopathological analysis with fast preliminary screening. We examine the feasibility of using X-ray diffraction measurements for this purpose; Methods: In this work, we obtained more than 6,000 diffraction patterns from 211 patients and examined both standard and custom-developed methods, including Fourier coefficient analysis, for their interpretation. Various preprocessing steps and machine-learning classifiers were compared to determine the optimal combination; Results: We demonstrated that benign and cancerous clusters are well-separated, with specificity and sensitivity exceeding 0.9. For wide-angle scattering, the two-dimensional Fourier method is superior, while for small angles, the conventional analysis based on azimuthal integration of the images provides similar metrics; Conclusions: X-ray diffraction of biopsy tissues, supported by machine-learning approaches to data analytics, can be an essential tool for pathological services. The method is rapid and inexpensive, providing excellent metrics for benign/cancer classification.

Abstract: Background. Sarcopenic obesity, characterized by excess fat and reduced muscle mass/function, is linked to chronic inflammation and metabolic dysfunction. Methods. This study assessed a 2-month multidisciplinary residential program (MRP) for improving clinical and functional outcomes in 61 institutionalized obese Italian adults (mean age 60; 36 women, 25 men; BMI ≥30 with metabolic comorbidities). The MRP included personalized nutrition, physical activity, and psychological support. Outcomes included anthropometric, biochemical, body composition, and physical performance measures (via Short Physical Performance Battery [SPPB]), with sarcopenia risk evaluated using EWGSOP2 criteria. Results. Post-intervention, significant improvements were observed in SPPB scores (+0.93 units, p&lt;0.001), weight (-6.4 kg), BMI (-2.45 kg/m²), fat mass (-3.9 kg), visceral adipose tissue (-314.2 g), and fat-free mass index (-285.54 g; all p&lt;0.01). Glycemic control improved, with reductions in fasting glucose (-16.4 mg/dL), HbA1c (-0.81%), insulin (-2.77 mcU/mL), and HOMA-IR (-0.95; p&lt;0.05). Lipid profiles also improved: total cholesterol (-21.32 mg/dL), LDL (-12.10 mg/dL), and triglycerides (-39.07 mg/dL; all p&lt;0.001). Conclusion. The MRP effectively enhanced body composition, metabolic health, and physical function, underscoring its potential as a preferred strategy for managing sarcopenic obesity in institutional settings.

Abstract: Diabetic nephropathy (DN) is a serious complication of Diabetes mellitus. This clinical condition is diagnosed through detection of microalbuminuria. Molecular biomarkers such as MicroRNA-192 may play a role in early diagnosis of this condition. The objective of this study was to assess the serum concentration of MicroRNA-192 in different stages of DN in comparison to a group of healthy individuals. The study was a retrospective case-control study included three groups. Group I included patients with early DN, group II included patients with late DN and group III included healthy control subjects. Blood samples were obtained from each participant and subjected to full biochemical study including creatinine, albumin and detection of MicroRNA-192 by real time polymerase chain reaction. There was significant difference between MicroRNA-192 levels in the three groups (P=0.001). There was significant increase in MicroRNA-192 level in group I (1.35±7 0.5) compared to group II (0.65±7 0.2, P3=0.001) and group III (0.83±7 0.3, P1=0.001). There was significant reduction in MicroRNA-192 level in group II compared to group III (P2=0.001). The study of diagnostic accuracy of MicroRNA-192 in the patients revealed good accuracy in the differentiation of early DN from control subjects (sensitivity 62% and specificity 86%) and good accuracy in the differentiation of early from late DN (sensitivity and specificity each 82%). The present study highlights that MicroRNA-192 is a good diagnostic tool for early detection of DN. MicroRNA-192 correlates significantly with estimated glomerular filtration rate, albuminuria, and renal functions tests. MicroRNA-192 might play role in the development of DN.

Abstract: The rise of multidrug-resistant (MDR) Pseudomonas aeruginosa remains an unresolved and substantial challenge to public health, which highlights an urgent need for newer therapeutic strategies. Despite the availability of innumerable antibiotics that effectively eliminate bacterial infections, their unregulated consumption and overexploitation has promoted the development of multidrug resistance by inducing selection pressure. As the world progresses into the post-antibiotic era, antivirulence therapies that exploit a ‘disarm-don’t kill approach’ are gaining momentum as a promising alternative to existing antimicrobial regimens. In view of extensive research being conducted to explore alternate intervention strategies against P. aeruginosa, this review augments scientific literature on repurposing of Food and Drug Administration (FDA)-approved drugs as antivirulence agents, focusing on their ability to disarm quorum sensing (QS), suppress virulence factor production, and disrupt biofilm formation. Drugs from various categories, including but not limited to antifungals, antidiabetics, antihypertensives, antiparasitics, NSAIDs, and antibiotics have been reported to override QS circuitry and QS-regulated virulence pathways in P. aeruginosa through in vitro and in vivo studies. Further, pre-clinical studies with FDA-approved drugs have been substantiated by in silico analysis predicting strong binding affinities to key QS receptors of P. aeruginosa such as LasR, RhlR, and PqsR, underscoring their potential mechanisms of action. Besides, with the well-documented safety profiles, pharmacokinetics, and clinical efficacy of the existing drugs, this repurposing approach streamlines the drug development process, minimizes costs, and accelerates the transition to clinical application. This review underscores the transformative potential of drug repurposing as a cost-effective and sustainable solution to the escalating antimicrobial resistance crisis and advocates for further research to optimize and clinically validate these promising antivirulence therapies.

Abstract: Cave environments represent extreme and underexplored ecosystems where fungi play a crucial role in nutrient cycling and ecological dynamics. This study provides the first comprehensive assessment of fungal diversity in air samples from caves across Portugal, with six samples from five locations being assessed through culture-dependent and metabarcoding approaches. From the five bat roosts studied, eleven morphologically distinct fungal taxa were isolated, with genera such as Aspergillus, Penicillium, and Chaetomium identified. Concurrently, Oxford Nanopore sequencing of the internal transcribed spacer (ITS) region of fungal rDNA revealed 286 genera, with Aspergillus, Candida, and Calyptella dominating across sites. Diversity indices and community composition analyses, including Principal Coordinate Analysis (PCoA) and hierarchical clustering, highlighted distinct fungal profiles influenced by site-specific environmental factors and human activity. The data underscores the dual role of fungi in bat roosts as essential decomposers emphasizing their adaptability to oligotrophic conditions. These findings advance our understanding of subterranean fungal ecology and stress the need for targeted conservation efforts to protect cave ecosystems from anthropogenic impacts.

Abstract: We report an unusual case of a nonsmoker and hypertensive 72 years old male who was admitted in the Neurology Department of Clinical County Emergency Hospital Bihor, with a second transient ischemic attack. He was diagnosed two years before, with the occasion of the first stroke, with paroxismal atrial fibrillation and was treated with anticoagulants, on top of his antihypertensive medication. At that time carotid echocardiography revealed nonobstructive atherosclerosis and statin therapy was initiated in an intend to lower the initial 70 mg/dl LDL-cholesterol level under 55 mg/dl, as indicated by current guidelines. Cardioembolism was considered the mechanism of stroke at that time. Despite the medication and the LDL under 50 mg/dl, carotid atherosclerosis evolved to an important left internal carotid stenosis and transient ischemic attack reappeared two years later. It was difficult to know its mechanism, but probably carotid stenosis was the cause. The patient underwent medical treatment and endarterectomy with good outcome. To elucidate the reason of progressive atherosclerosis and to apply preventive treatment in this case was challenging. No chronic diseases were detected during the postoperative evaluation of the patient, except for early-stage periodontal disease, for which adequate preventive measures were applied. Considering that subclinical inflammation induced by periodontal disease can induce the progression of atherosclerosis, chronic treatment with colchicine was added, with favorable outcome.

Abstract: Beyond its immunological role, colostrum has emerged as a promising, non-invasive source of bioactive factors, including Mesenchymal Stromal Cells (MSCs). This study represents the first attempt to isolate and characterize MSCs from equine colostrum (C-MSCs) and assess their potential use in veterinary regenerative medicine. Colostrum (n=6) was collected immediately after delivery, centrifuged, and recovered cells cultured under standard conditions. C-MSCs displayed plastic adherence and heterogeneous morphology, including spindle-shaped and epithelial-like cells. PDT values varied among samples, and 4/6 showed rapid proliferation (< 2 days). CFU assays confirmed clonogenic potential, though significant inter-sample variability was observed (p< 0.05). Spheroid formation assays revealed differences in cell-cell adhesion: 4/6 samples formed stable spheroids within four days. Migration assay showed significant variability (p< 0.05): 1/6 achieved complete wound closure within 72 hours, whereas 5/6 reached ~30% at 96 hours. Differentiation assays confirmed trilineage potential, with all samples staining positive for adipogenic, chondrogenic, and osteogenic differentiation. RT-PCR confirmed MSC marker expression, while hematopoietic markers were absent. MHC-I expression was weak in 5/6 samples, whereas MHC-II was consistently negative. These findings support equine colostrum as a viable MSC source, though variability requires further validation with larger samples. Additional research is needed to investigate C-MSCs' immunomodulatory properties and therapeutic potential.

Abstract: Infectious diseases remain a significant global health challenge, intensified by emerging pathogens, antimicrobial resistance, and limited healthcare access in low-resource settings whereas the emergence of Artificial Intelligence (AI) has transformed the way of infectious disease management by enhancing diagnostics, surveillance, drug discovery, and personalized treatment strategies. AI-driven approaches like Machine Learning (ML), Natural Language Processing (NLP) and deep learning, have facilitated early identification of disease, optimized healthcare resource allocation, and accelerated both the vaccine and drug development. AI powered diagnostic tools, such as computer vision-based medical imaging models and real-time epidemiological surveillance systems, have been instrumental in pandemic response efforts. Moreover, use of AI improved Anti-Microbial Resistance (AMR) monitoring, ensuring timely intervention against drug-resistant infections. More specifically, AI is developing at unprecedented scale which is being adopted and deployed even faster in every sphere of life globally. Despite its beneficial potential, there are some challenges like data privacy, ethical concerns, and infrastructure limitations causing barriers to widespread AI adoption in healthcare. Therefore, there is a requirement for collective global efforts to establish governance and standards that uphold the shared values, and address risks and build trust. Thus, the present review explores the current advancements, challenges, and future directions of AI in infectious disease management, highlighting its transformative impact on global health security.

Abstract: Stroke-prone spontaneously hypertensive rats (SHRSP) are widely used as a model to study cerebral small vessel disease (CSVD) and its association with chronic hypertension. This study investigated the relationship between metabolic, cardiovascular, and neuronal comorbidities in 32-week-old SHRSP rats versus Wistar-Kyoto (WKY) controls, with a focus on oxidative stress, inflammation, and metabolic alterations. Despite hypertension and cardiac and renal hypertrophy, no significant cerebral vascular changes or microbleeds and no cerebral edema were detected in SHRSP. NMR-based urinary metabolomics revealed reduced gut microbiome-derived metabolites, such as p-cresylglucuronide, hippurate, and phenylacetylglycine, alongside increases in methylamine and dimethylamine. These findings reflect gut dysbiosis and altered microbial composition in hypertensive conditions. Elevated markers of oxidative stress, including thiobarbituric acid-reactive substances, and increased expression of NADPH oxidase (NOX) 2 and NOX4 in peripheral tissues suggested oxidative damage in SHRSP rats. Astrocytic hyperreactivity, indicated by increased expression of glial fibrillary acidic protein in brain cortex and hippocampus, was suggestive of neuroinflammatory responses. Our findings highlight complex interplay between hypertension, metabolism, and neuroinflammation in SHRSP, an experimental model of co-morbidities.

Abstract: Objective: Lung cancer remains the leading cause of cancer-related mortality worldwide, with significant resistance to conventional therapies, highlighting the urgent need for novel therapeutic strategies. Moringa oleifera (M. oleifera), a medicinal plant rich in diverse bioactive compounds, has shown promising potential for anti-lung carcinoma activity. This study investigates the molecular mechanisms underlying the therapeutic effects of M. oleifera bioactive compounds through an integrated systems biology and molecular docking approach. By constructing comprehensive compound-target-pathway networks, we aim to elucidate the multitarget pharmacology of M. oleifera compounds, providing valuable insights into their potential as therapeutic candidates. Methods: Bioinformatics tools were used to identify 180 phytochemicals from M. oleifera, filtered using Lipinski’s Rule of Five and ADMET properties, yielding 14 lead compounds. Protein-protein interaction (PPI) analysis identified 89 overlapping lung cancer targets, with EGFR being the most enriched in pathway enrichment analysis. Results: In the analysis, Caffeic acid showed the highest binding affinity (-28.97 kcal/mol) with EGFR through molecular docking and maintained stability during molecular dynamics simulations. This interaction also modulates 12 pathways critical to lung cancer, including MAPK, JAK-STAT, and PI3K/AKT pathways. The overall result suggests that Caffeic acid is an EGFR-mediated oncogenic signalling inhibitor. Conclusion: Caffeic acid is a potential candidate for lung cancer therapy, warranting further experimental validation to translate these findings into clinical applications.

Abstract: The genus Fusicolla belongs to the order Hypocreales and the family Nectriaceae. These fungi, mainly saprobes, colonise various substrates such as soil, decaying wood and decomposing organic matter. As part of a study of fungal communities in soils contaminated by polycyclic aromatic hydrocarbons (PAHs), a new species, here named Fusicolla massiliensis sp. nov. Fo821, was isolated from an environmental sample and cultured on FastFung medium. The identification and description of this species was carried out using a combination of morphological, microscopic, phenotypic and genetic approaches. The molecular analysis included the sequencing of four genetic regions: the internal transcribed space (ITS), a fragment of the β-tubulin gene (tub2), the rpb2 gene, and the D1/D2 region of the large ribosomal subunit (LSU). These sequences revealed a significant genetic distance from other known species of the genus Fusicolla, confirming its status as a new species. Phenotypic analyses established the substrate assimilation profiles and specific chemical characteristics of Fusicolla massiliensis Fo821, while optical and electron microscopic observations highlighted its unique morphology. Finally, an antifungal susceptibility profile was established using advanced methods. This study makes a valuable contribution to the taxonomy of the genus Fusicolla and sheds light on its adaptation to contaminated environments.

Abstract: Background/Objectives: Cancer cells exhibit metabolic reprogramming, enabling them to switch between glycolysis and oxidative phosphorylation for ATP generation necessary for survival, proliferation and metastasis. This adaptability allows cancer cells to evade conventional therapy options that target only one metabolic pathway among others and lead to cancer resurgence and treatment resistance. The goal of this investigation was to evaluate the dual inhibition of these metabolic pathways with Annonacin and 2-DG in individual and combination modalities on A549 and NL20 cells to develop selective therapies for cancer cells, sparing normal cells. This dual attack was hypothesized to improve treatment effectiveness with triggering of cancer cell death by exploiting the metabolic vulnerabilities, disrupting glucose metabolism, modulating oxidative stress and inducing apoptosis through generation of reactive oxygen species (ROS) mediated DNA damage. Methods: The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]-MTT and clonogenic assays were employed to assess the viability and proliferation capacity, respectively in A549 cancer and NL20 normal cells exposed to individual and combination treatment of Annonacin and 2-DG. Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) assays were employed to evaluate treatment mediated oxidative stress. Results: The combination treatment showed enhanced cytotoxicity compared to individual application, while normal cells exhibited differential and selective response. Conclusions: These findings provided the preclinical evidence for the potential therapeutic application of Annonacin and 2-DG as a dual metabolic targeting strategy for NSCLC. Future in vitro and in vivo research are necessary to understand the underlying mechanisms in detail and potentially translate them into treatment against NSCLC.

Abstract: The “Mystery” of the origin of life has not been solved still now. In this review article, the reason, why the origin of life has not been solved, is discussed from three standpoints, (1) formation process of the first gene, (2) formation process of the first genetic system, (3) formation process of the first fundamental life system. From the results, it has been under-stood that the main reasons are because the studies on the origin of life have been chiefly carried out under the RNA world hypothesis based on the “gene/replicator-first hypothesis”. Successively, it was investigated whether or not the “mystery” of the origin of life could be solved by [GADV]-protein world hypothesis or GADV hypothesis based on the “protein/metabolism-first hypothesis”. Consequently, it has been confirmed that the steps to from chemical evolution to the emergence of life can be reasonably explained, if the formation process of the first gene was started from not mature but immature [GADV]-protein, actually [GADV]-peptide aggregates. It was also found that the three problems (1)~(3) is one problem, that is, the second and the third problems can be simul-taneously solved, if the first problem (1), “How was the first gene formed?” could be solved. Furthermore, it has been found that the formation process of the first funda-mental life system leading to the emergence of life must be formed by piling up the five members onto the immature [GADV]-protein according to the bottom-up manner.