In Sub-Saharan Africa, despite poverty, chronic hunger and food insecurity, traditional eating has been related to positive health outcomes and sustainability. There is little health research on diet quality based on what African people consume. The defining characteristics of the traditional African cuisine are the richness in herbs and spices, fermented foods and beverages, and healthy and whole ingredients used. However, as countries in this region become more economically developed, there is a shift to “modern” occidental foods rich in saturated fats, sugar and sweeteners. As a result, there are increased incidences of previously unreported ailments due to unbalanced diet. The regular practice of infinite international aid to the region to curb food insecurity has been unsustainable, ineffective and with no end in sight. Local increase in production and productivity is imperative. Protein rich foods in dietary guidelines enhance only those of animal or plant sources while rich protein sources such of mushroom, has been absent in these charts. This article considers the valorisation of traditional African foods and the importance of establishing an African Food-Based Dietary Guidelines (AFBDGs), an unprecedented Food Pyramid, along with the added emphasis on the potential of African mushrooms, which may play a role in shielding Sub-Saharan Africans against the side-effects of a western stylish diet and promote health. It enhances the preventive role of mushrooms in viral diseases and other disorders.

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although very limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which is able to stabilize the effector cells becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allows a great improvement in the management of asthma.

Zika virus (ZIKV), without a vaccine or no effective treatment approved as yet, have globally spread since the past century. The infection caused by ZIKV in humans has changed progressively from mild to subclinical in the last years, causing epidemics with greater infectivity, tropism towards new tissues, and other related symptoms as a product of various emergent ZIKV-host cell interactions. However, it is still unknown why or how the RNA genome structure impacts those interactions in differential evolutionary origin strains. Moreover, genomic comparison of ZIKV strains from the sequence-based phylogenetic analysis is well known, but differences from RNA structure comparisons are less known. Thus, in order to understand the RNA genome variability of lineages of various geographic distributions better, 412 complete genomes in a phylogenomic scanning were used for studying the conservation of structured RNAs. We found specific genomic regions, which highlight their patterns of conserved RNA structures at the level of inter-geographical comparisons. We have proposed these structures as candidates for further experimental validation to establish their potential role in vital functions of the viral cycle of ZIKV and their possible associations with the singularities of different outbreaks that occurred in specific geographic regions.

Although rRT-PCR is the gold standard method for SARS-CoV-2 detection, some factors, such as amplification inhibitors presence, lead to false-negative results. Here we describe differences between rRT-PCR results for SARS-CoV-2 infection in normal and diluted samples, simulating the need for dilution due to amplification inhibitors presence. Viral RNA extraction of nasopharyngeal swabs samples from 20 patients previously detected as 'Negative' and 21 patients detected as 'Positive' for SARS-CoV-2 was realized with the EasyExtract DNA-RNA (Interprise®). rRT-PCR was realized with OneStep/COVID-19 (IBMP) kit with normal and diluted (80µl of H₂O RNAse free) samples, totaling 82 tests. The results indicate that there is an average variation (ɑ < 0.05) delaying Cq between the amplification results of internal control (IC), N Gene (NG), and ORF-1ab (OF) of 1.811 Cq, 3.840 Cq, and 3.842 Cq, respectively. The extraction kit does not completely purify the inhibitor compounds, therefore non-amplification by inhibitors may occur. In this study, we obtained a 19.04% false-negative diagnosis after sample dilution, and this process reduces the efficiency of rRT-PCR to 29.80% for detecting SARS-CoV-2. Knowing the rRT-PCR standards of diluted samples can help in the identification of false-negative cases, and consequently avoid a wrong diagnosis.

The COVID-19 global pandemic is now a public health emergency in Morocco. Reports on factors associated with prolonged viral shedding are not consistent. In this retrospective laboratory based study, time to RNA negative conversion is reported in a series of 129 patients monitored in a single laboratory in Casablanca. Risk factors associated with delayed negative conversion have been evaluated, by chi-squared test. Median delay of negative conversion was 22.5 days (IQR 17.75-29.0) from illness onset. Neither gender nor age were particularly associated with delayed viral clearance. Delayed time to hospital admission and disease severity were associated with prolonged viral shedding in this series. We recommend early diagnosis and treatment onset to reduce time to viral clearance and transmissibility of SARS-CoV-2 virus.

The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress and fatality. At present, the global case fatality rate of COVID-19 laboratory confirmed cases is ~4.7% ranging from ~0.3-0.4% in Chile and Israel to ~10.8% in Italy. To address this global crisis, up-to-date information on the viral genomics and transcriptomics is crucial for understanding the origins and global dispersal of the virus, providing insight into viral pathogenicity, transmission and epidemiology, and enabling strategies for therapeutic interventions, drug discovery and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.

Zika virus (ZIKV) is an emerging human mosquito-transmitted pathogen of global concern, known to be associated with complications such as congenital defects and neurological disorders in adults. ZIKV infection is associated with induction of cell death. However, previous studies suggest that the virally-induced apoptosis occurs at a slower rate compared to the course of viral production. In this present study, we investigated the capacity of ZIKV to delay host cell apoptosis. We provide evidence that ZIKV has the ability to interfere with apoptosis whether it is intrinsically or extrinsically induced. In cells expressing viral replicon-type constructions, we show that this control is achieved through replication. Finally, our work highlights an important role for anti-apoptotic Bcl-2 family protein in the ability of ZIKV to control apoptotic pathways, avoiding premature cell death and thereby promoting virus replication in the host-cell.

The Zika virus (ZIKV) is a mosquito-borne Flavivirus and can be transmitted through an infected mosquito bite or through human-to-human interaction by sexual activity, blood transfusion, breastfeeding or perinatal exposure. After the 2015-2016 outbreak in Brazil, a strong link between ZIKV infection and microcephaly emerged. ZIKV specifically targets human neural progenitor cells, suggesting that proteins encoded by ZIKV bind and inactivate host cell proteins leading to microcephaly. Here, we present a systematic annotation of interactions between human proteins and the seven non-structural ZIKV proteins corresponding to a Brazilian isolate. The interaction network was generated by combining tandem-affinity purification followed by mass spectrometry with yeast two-hybrid screens. We identified 150 human proteins, involved in distinct biological processes, as interactors to ZIKV non-structural proteins. Our interacting network is composed of proteins that have been previously associated with microcephaly in human genetic disorders and/or animal models. This study builds on previously published interacting networks of ZIKV and genes related to autosomal recessive primary microcephaly to generate a catalog of human cellular targets of ZIKV proteins implicated in processes related to microcephaly in humans. Collectively, this data can be used as a resource for future characterization of ZIKV infection biology and help create a basis for the discovery of drugs which may disrupt the interaction and reduce the health damage to the fetus.

Viruses are the most abundant biological entities in aquatic ecosystems and harbor an enormous genetic diversity. While their great influence on the marine ecosystems is widely acknowledged, current information about their diversity remains scarce. A viral metagenomic analysis of three water samples was conducted from sites on the South Scotia Ridge (SSR) near the Antarctic Peninsula, during the austral summer 2016. The taxonomic composition and diversity of the viral communities were investigated and a functional assessment of the sequences was determined. Phylotypic analysis showed that most viruses belonging to the order Caudovirales, especially the family Podoviridae (41.92-48.7%), similar to the viromes from the Pacific Ocean. Functional analysis revealed a relatively high frequency of phage-associated and metabolism genes. Phylogenetic analyses of phage TerL and Capsid_NCLDV (nucleocytoplasmic large DNA viruses) marker genes indicated that many sequences associated with Caudovirales and NCLDV were novel and distinct from known phage genomes. High Phaeocystis globosa virus virophage (Pgvv) signatures were found in SSR area and complete and partial Pgvv-like were obtained which may have an influence on host-virus interactions. Our study expands the existing knowledge of viral communities and their diversities from the Antarctic region and provides basic data for further exploring polar microbiomes.

Hepatitis C virus (HCV) represents a challenging global health threat in ~200 million infected individuals. Clinical data suggests that only ~10-15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts a myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence that includes, but not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here, we discussed a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.

Background: Antiphospholipid antibodies (aPL) are a laboratory criterion for the classification of antiphospholipid syndrome (APS), and are known to cause clinical symptoms: vascular thrombosis or obstetric complications. It is suggested that aPL may be associated with thromboembolism in severe COVID-19 cases. Aim: to combine clinical data with aPL findings at 4 time points (admission, worsening, discharge, 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. Methods: current and past history of thrombosis and obstetric complications; aPL determined at 4 time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI) and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG or IgA isotypes. Results: 111 patients with COVID-19 pneumonia were enrolled. During hospitalization, 7 patients died, 3 of them due to pulmonary artery thromboembolism (none was aPL positive). Only one of the five who developed pulmonary artery thrombosis was aPL positive. Of 9/101 patients with a history of thrombosis, 5 had arterial thrombosis and none was aPL positive at admission and follow-up; 4 had venous thrombosis and one was aPL positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPL positive at discharge only, compared to 26.1% without history of thrombosis (p=0.05). Conclusions: aPL were not associated with fatal outcomes and vascular thrombosis; aPL were transiently positive in more than half of patients with a history of thrombosis.

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

The West-African variety of Sorghum bicolor leaf sheath (SBLS) Jobelyn® is a natural remedy, which has gained international recognition for its anti-anemic effect and energy boosting qualities in debilitating diseases. The widespread use of traditional medicine in the region usually confirms its safety, but not its efficacy or deep assessment of their pharmacological properties. The other major issue for herbal-based treatments is the lack of definite and complete information about the composition of the extracts. Despite limitations, efforts have been made in isolation and characterisation of active compounds in this specie of sorghum showing various subclasses of flavonoids including apigeninidin, a stable 3-deoxyanthocyanidin and potential fungal growth inhibitor, which accounts for 84% of the total extract. Non-clinical in vitro and in vivo studies support previous indications that this variety of Sorghum bicolor possesses several biologically active compounds with potent antioxidant, anti-inflammatory, anti-aging and neuro-protective properties. Clinical studies show that SBLS has the ability to boost hemoglobin concentrations in anemic conditions and most remarkably to increase CD4 count in HIV-positive patients. The multiple effects and high safety profiles of this extract may encourage its development as a therapeutic agent for the treatment of anemia, chronic inflammatory conditions or in the symptomatic management of HIV infections. This review describes the potential therapeutic aspects of SBLS extract and its potential benefits.

Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declined responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5'end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5’ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I or MDA5 receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host-cell interactions driving the development of acute or persistent EV-B infections.

Background The evolution of treatment patterns in neovascular age-related macular degeneration (nAMD) warrants investigation into the impact of patients’ adherence to anti-vascular endothelial growth factor (VEGF) treatment on visual outcomes. This retrospective, non-randomized, non-comparative study aimed to investigate real-world adherence to anti-VEGF treatment. Methods Patients (eyes) (≥ 50 years) with a diagnosis of nAMD who had a first injection of aflibercept or ranibizumab between January 2016 and December 2018 and 12 months of follow-up were included. Visual acuity (VA; logarithm of the minimum angle of resolution letters) and duration of injection intervals were recorded. Adherence was defined as < 20% of visits deviating from the schedule by ≥ 14 days. Results Overall, 133 patient eyes were included: 129 adherent, 4 non-adherent. Mean (± standard deviation) baseline VA was 57.0 (± 23.6) and 53.8 (± 35.3) letters in adherent and non-adherent patient eyes, respectively. Mean change in VA by month 12 was higher in adherent (6.3 letters) than non-adherent patient eyes (−11 letters). In non-adherent patient eyes, no improvement in VA was recorded following completion of the loading period (month 3). Compared with the previous visit, adherent visits were associated with a mean increase in VA of 0.67 letters and non-adherent visits with a decrease of 2.30 letters. Conclusions These results emphasize the importance of adherence to appropriate dosing regimens to optimize visual outcomes in patients with nAMD.

Bangladeshi medicinal plants (BMP) have been used as traditional medicinal plants to treat chronic inflammatory diseases, but the antioxidant and anti-inflammatory effects of the bark of BMP are not yet known. The objective of this study was to determine antioxidant and anti-inflammatory activities using methanolic extracts of bark obtained from 15 medicinal spices of Bangladesh plants. The bark methanol extracts of BMP evaluated the total antioxidant activity and anti-inflammatory effect of lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. Among the 15 bark extracts of BMP, Albizia odoratissima (A. odoratissima), Engelhardia spicata (E. spicata), and Shorea robusta (S. robusta) showed the highest total phenolic contents and total antioxidant capacity by reducing free radicals scavenging activity. In particular, the three bark extracts significantly reduced the mRNA expression of LPS-induced inflammatory cytokines and inflammation-inducible enzymes in macrophages. Also, the mRNA expression of NADPH oxidase 2 was significantly suppressed by three bark extracts in LPS-induced RAW 264.7 macrophages. The results suggest that among the 15 bark extracts obtained from medicinal plant in Bangladesh, three bark extracts of A. odoratissima, E. spicata, and S. robusta exert total antioxidant capacity by reducing free radicals scavenging activity and inhibitory effects on LPS-stimulated inflammation in macrophages.

Two-dimensional (2D) ice I is an atomic-level ice that is composed of two interlocked atom-ic layers saturated with hydrogen bonds. It has recently been experimentally observed but its properties have yet to be clarified. Accordingly, we theoretically studied the hydrophobic properties of 2D ice I. On the contrary, simulation of a hydrogen fluoride molecule on a 2D ice surface manifested that it destroyed the 2d ice structure and connected new hydrogen bonds with water molecules. Investigations of the interfacial effect between 2D and three-dimensional (3D) ice films indicated that the network structure of 2D ice was not de-stroyed by a 3D ice surface, as the former was saturated with hydrogen bonds. However, the surface of 3D ice reorganized to form as many hydrogen bonds as possible. Thus, the 2D ice film was hydrophobic and inhibited the growth of 3D ice. This shows that if 2D ice can be produced on an industrial scale, it could be used as an anti-3D-icing agent under low tem-perature.

This work is based on identifying the analysis techniques used to evaluate the antioxidant and anti-inflammatory effects using the zebrafish model. In this context, a literature review was performed with the Web of Science database. We used the terms zebra fish, antioxidant, anti-inflammatory, model, and Danio rerio. Fifty articles were reviewed, of which thirty-three were chosen to perform this review and were classified according to the source of plant extracts, compounds extracted from plants, chemical compounds, and other sources. This paper is an effort to provide a literature review on zebrafish models and elucidate their pros and cons to evaluate anti-inflamatory and antioxidant activity.

The purpose of this scoping review was to examine the literature on the use of anti-gravity treadmill and its effects on lower limb motor functions in children and adolescents with locomotor impairments. Four databases (MEDLINE, CINAHL, Embase, Web of Science) were searched for articles from inception to August 2021. Inclusion criteria were: (1) experimental or quasi-experimental studies using the anti-gravity training as the primary intervention; (2) studies conducted in paediatricpediatric participants; (3) articles reporting outcomes related to the lower limb functions; and (4) studies published in French or English. Fifteen articles were included in the review. Studies included children and adolescents aged 4–18 years with locomotor impairments. The intervention duration was ranged from 2 and to 12 weeks, with 2-5 sessions per week. Included studies showed reported that anti-gravity training induces improvements in muscle strength, balance, spatiotemporal gait parameters, and walking endurance in children with locomotor impairments. This review provides relevant information about the modalities, outcomes and limits associated with the anti-gravity training protocol reported in the literature. Overall, the anti-gravity treadmill training could be viewed as a valuable training modality for children with cerebral palsy. However, more precise, and comprehensive description of anti-gravity rehabilitation protocols would be useful.

Acquired Immunodeficiency Syndrome (AIDS) which is chiefly originated by a retrovirus named Human Immunodeficiency Virus (HIV), has influenced about 70 million populations worldwide. Even though several advancements have been invented in the field of antiretroviral combination therapy, still HIV has become the dominant reason for death in South Africa, for example. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. In the present day, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate the drugs obtained from natural plants as well as the synthetic derivatives that have been derived from the natural compounds by various chemical reactions. Several plants such as Andrographis paniculata, Dioscorea bulbifera, Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity showing more potent anti-HIV activity along with their structures, SARs & important key findings.

As the time passes the modification in technology world lead to the evaluation in mobile application as well. With evaluation in mobile industry it is an open challenge for software quality researcher that how to enhance software quality to meet the needs of changes? Quality assurance play a key role in differentiating good application from bed application. With the continuous evaluation of mobile application developing process should be quick and efficient to comply with user requirements and satisfaction. While the listed requirement leads to bad design choices known as antipatterns, which in turn affect the reliability of the code. A tool based method PAPRIKA is used in the proposed re-search to identify and monitor these antipatterns together with a two-step assessment model for software quality assurance and object oriented software quality matrix.

The iridoids of H. diffusa play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism is lack of study. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Its anti-inflammatory mechanism was confirmed by in intro experiment and molecular docking analysis. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.

Background and Objectives: In the current Covid-19 pandemic, children below the age of 12 could manifest Covid-19 symptoms and serve as a reservoir for the virus in the community. The present study was conducted to evaluate the reactogenicity, and immunogenicity of BBIBP-CorV, prior to involving this age group in the vaccination program in the kingdom of Bahrain. Subjects and Methods: The study included 582 children from 3 to 12 years old of Bahraini and non-Bahraini nationality, all of which contributed to the reactogenicity study. Of those, 401 contributed to the immunogenicity study. All children received 2 doses of BBIBP-CorV inactivated virus 3 weeks apart. To assess reactogenicity, children were followed up for 5 weeks to evaluate any vaccine-related adverse events (AE). To assess immunogenicity, blood was collected on day 0 and day 35 to assess antibody titer against S, N, and neutralizing antibody. Results: Of the 582 participants, (45.4%) were female, (54.61%) were male, with 49% in 9-12 age group. Of the 401 children contributing to the immunogenicity study, 274 (68.3%) had no prior exposure to Covid-19. The overall incidence of AE was 27.7%. No significant difference was found among different age groups. The most frequent AE was local (at the injection site) and occurred in 16% of children, followed by fever in 9.3%. No serious adverse events were reported. The Seroconversion rate was 100% among children with no prior exposure to Covid-19. Children with previous Covid-19 exposure had higher averages of anti-S (2379 U/ml compared to 409.1), anti-N (177.6 U/ml compared to 30.9) and neutralizing antibody (93.7 U/ml compared to 77.1) than children with no prior exposure at day 35. Conclusions: Two doses of COVID-19 BBIBP-CorV on the subjects aged between 3 to 12 has good safety and tolerance and can induce an effective immune response and neutralizing antibody titer.

The simplistic morphological characteristics of the Carica papaya, papaya or ‘pawpaw’ should not be the cause for underestimating its potential as a nutraceutical. The market for papaya has been expanding at a staggering rate, partly due to its applicability as a biofortified product, but mostly for its phytochemical properties and traditional health benefits. Recent characterization studies have showed that the entirety of papaya or using a formulation of fermented papaya promotion (FPP) displays effective free radical scavenging abilities, thought to be influenced by its phenolic, carotenoids, flavonoid or amino acid profile. Aiming at reducing the impact of free radical-induced oxidative damage in the human system, the antioxidant properties of FPP have been found to potently target a broad spectrum of diseases ranging from neurological impairments such as senile dementia to systemic diseases, to its interference at the cellular level and support of normal biological ageing processes. FPP has thus been extensively investigated for its ability to exert cellular protective effects and reduce oxidative stress via mitigation of genetic damage, lipid peroxidation and enzymatic inactivation in diseases. Oxidative stress reduction strategies using FPP and its holistic approach in disease prevention and management, with a focus on diabetes, cancer and cognitive health, contributes unequivocally to wellness in an aging population.

In mesoscale eddies, chemical properties and biological composition are different from those in surrounding water, due to their unique physical processes. It is unclear how physical-biological coupling occurs in warm-core eddies, particularly since no study has examined the relationship between bacteria and viruses. The purpose of the present study was to examine the influence of anticyclonic warm eddy on the relationship between bacterial and viral abundances as well as viral activity (viral production) in different depths. In the core of warm eddy, bacterial abundance (0.48 to 2.82 ×105 cells mL−1) fluctuated less than that of the outside eddy (1.12 to 7.03×105 cells mL−1). In particular, there was four-folds higher of viral-bacterial abundance ratio (VBR) estimated within the eddy below DCM than the outside eddy. We suggest that prevailing physical forces with downwelling at the center of the anticyclonic warm eddy, viruses can also be transmitted into the deep ocean directly through adsorption on particulate organic matter during sinking. Overall, our findings provide valuable insights into the interaction between bacterial and viral communities and their ecological mechanism within the warm eddy.

Lyme disease is the most common tick-borne illness in the United States, Europe, and Asia. Borrelia burgdorferi, a spirochete bacterium transmitted by the tick vector Ixodes scapularis, causes Lyme disease in the U.S. If untreated, Lyme arthritis, carditis, and meningitis will occur. Given the absence of a human Lyme disease vaccine, we developed a vaccine using the rabies virus vaccine vector, BNSP333, and an outer surface borrelial protein BBI39. To incorporate BBI39 into the RABV virion, we generated a chimeric BBI39 antigen, BBI39RVG, by fusing it with the final amino acids of the RABV glycoprotein. Here we demonstrated that BBI39RVG antigen was incorporated into the RABV virion, and mice vaccinated with our RABV-BBI39RVG vaccine induced high amounts of BBI39-specific antibodies which are maintained long-term. The BBI39 antibodies neutralized Borrelia in vaccinated mice when challenged with Borrelia burgdorferi by either syringe injection or infected ticks, and reduced Lyme disease pathology.

Respiratory viral infections, including influenza, respiratory syncytial virus (RSV), and, more recently, the coronavirus disease 2019 (COVID-19) pandemic, continue to pose significant global health threats. Conventional treatments for these infections often face challenges such as limited efficacy, the emergence of drug-resistant strains, and the requirement for frequent administration. In recent years, nanobodies have emerged as a promising class of therapeutic agents due to their unique properties, including small size, high stability, and specific binding capabilities. This mini-review article focuses on the application of nanobodies as spray and aerosol particles for the treatment of respiratory viral infections. Furthermore, we highlight the remarkable efficacy of nanobodies in preclinical and clinical studies against respiratory viruses, including their ability to neutralize viral particles, inhibit viral replication, and modulate the host immune response. We discuss the potential advantages of using nanobodies as inhalable formulations, including their improved delivery to the respiratory tract, enhanced stability in aerosol form, and reduced systemic side effects. Additionally, we explore the various strategies employed to engineer nanobodies for optimal aerosol delivery, such as conjugation to carrier particles or formulation as dry powders. We also examine the potential challenges and limitations associated with the development of nanobody-based aerosol therapies, including production scalability, cost-effectiveness, and regulatory considerations.

In May 2022, WHO reported an outbreak of Mpox in several European countries which were previously Mpox free. Mpox (formerly known as monkeypox) is a zoonotic viral disease endemic in Central and West Africa. The sudden emergence of Mpox outside Africa and its subsequent rapid spread lead the WHO to declare the outbreak as Public Health Emergency of International Concern. As of May 15, 2023, a total of 87,704 confirmed cases and 140 deaths had been reported from 111 countries and territories worldwide. Looking back on this outbreak one year later, several important questions have arisen. Here, we address these questions using the classic five Ws: What, When, Where, Who and Why? We discuss these questions and outline what needs to be done to prevent, or at least minimize, outbreaks from emerging and re-emerging viral infection.

The Infectious and Tropical Diseases Department of University of Brescia organized free rapid screening tests for HIV and HCV as part of the Fast Track City commitment. A cross-sectional study was conducted, consisting of an anonymous, multiple-choice questionnaire that was administered to individuals who underwent the screening or consultation. The study aimed to compare knowledge and attitudes towards HIV and HCV between age groups (18-40 vs. >40) and sexual orientations (heterosexual vs. LGBTQ+). Overall, 333 questionnaires were completed. Individuals over the age of 40 and those who identified as heterosexual had the lowest level of knowledge about HIV transmission (7.9% and 30% respectively), undetectable=untransmittable (19.7% and 39.4% respectively) and PrEP (9.2% and 18.2% respectively). They were also less willing to cohabit with people with HIV (PLHIV). Only 9.6% of the population demonstrated high levels of knowledge for both HIV and HCV. People over the age of 40 had the largest gaps in knowledge and would benefit the most from educational and prevention interventions.

Gene therapy has seen major progress in recent years. Viral vectors have made a significant contribution through efficient engineering for improved delivery and safety. A large variety of indications such as cancer, cardiovascular, metabolic, hematological, neurological, muscular, ophthalmological, infectious diseases, and immunodeficiency have been targeted. Viral vectors based on adenoviruses, adeno-associated viruses, herpes simplex viruses, retroviruses including lentiviruses, alphaviruses, flaviviruses, measles viruses, rhabdoviruses, Newcastle disease virus, poxviruses, picornaviruses, reoviruses, and polyomaviruses have been used. Proof-of-concept has been demonstrated for different indications in animal models. Therapeutic efficacy has also been achieved in clinical trials. Several viral vector-based drugs have been approved for the treatment of cancer, and hematological, metabolic, and neurological diseases. Moreover, viral vector-based vaccines have been approved against COVID-19 and Ebola virus disease.

Systematic reviews of 591 primary studies of the modes of transmission for SARS-CoV-2 show significant methodological shortcomings and heterogeneity in the design, conduct, testing and reporting of SARS-CoV-2 transmission. While this is partly understandable at the outset of a pandemic, evidence rules of proof for assessing the transmission of this virus are needed for pre-sent and future pandemics of viral respiratory pathogens. We review the history of causality as-sessment related to microbial etiologies with a focus on respiratory viruses and suggest a hierar-chy of evidence to integrate clinical, epidemiologic, molecular and laboratory perspectives on transmission. The hierarchy, if applied to future studies, should narrow the uncertainty over the twin concepts of causality and transmission of human respiratory viruses. We attempt to address the translational gap between the current research evidence and the assessment of causality in the transmission of respiratory viruses with a focus on SARS-CoV-2. Experimentation, consistency and independent replication of research alongside our proposed framework provide a chain of evidence that can reduce the uncertainty over the transmission of respiratory viruses and increase the level of confidence in specific modes of transmission, informing the measures that should be undertaken to prevent transmission.

The fate of a viral infection in the host begins with various types of cellular responses, such as abortive, productive, latent, and destructive infections. Apoptosis, necroptosis, and pyroptosis are the three major types of regulated cell death mechanisms that play critical roles in viral infection response. Cell shrinkage, nuclear condensation, bleb formation, and retained membrane integrity are all signs of osmotic imbalance-driven cytoplasmic swelling and early membrane damage in necroptosis and pyroptosis. Caspase-driven apoptotic cell demise is considered in many circum-stances as an anti-inflammatory, and some pathogens hijack the cell death signaling routes to initiate a targeted attack against the host. In this review, we selected mechanisms by which viruses interfere with cell death are discussed in-depth and are used to illustrate the general principles and cellular signaling mechanisms of virus-host specific molecule interactions.

HIV-associated neurocognitive disorder (HAND) is an array of neurocognitive changes associated with HIV infection, and the roles of microRNAs in HAND are not completely revealed yet. Based on published data and publicly available databases, we constructed an integrated miRNA-mRNA network involved in HAND. Bioinformatics analyses, including gene ontology, network analysis, and KEGG pathway analysis, were applied for further study of the network and the genes of the network. The axon guidance KEGG pathway, three genes NTNG1, EFNB2, CXCL12, and 17 miRNAs which regulates them, are spotlighted in our study. This study provides new perspectives to the knowledge of miRNAs’ roles in the process of HAND, and our findings provided potential therapeutic targets and clues of HAND.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic still persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the Spike surface protein of the virus are regularly observed in the new variants, potentializing the emergence of novel viruses with different tropism from the current ones, which may change the severity and symptoms of the disease. Growing evidence has shown that mutations are being selected in favor of variants that are more capable of evading the action of neutralizing antibodies. In this context, the most important factor guiding the evolution of SARS-CoV-2 is its interaction with the host’s immune system. Thus, as current vaccines cannot block the transmission of the virus, measures complementary to vaccination, such as the use of masks, hand hygiene, and keeping environments ventilated remain essential to delay the emergence of new variants. Importantly, in addition to the involvement of the immune system in the evolution of the virus, we highlight several chemical parameters that influence the molecular interactions between viruses and host cells during invasion and are also critical tools making novel variants more transmissible. In this review, we dissect the impacts of the Spike mutations on biological parameters such as (1) increase of Spike binding affinity to hACE2; (2) bound time for the receptor to be cleaved by the proteases; (3) how mutations associate with increase of RBD up-conformation state in the Spike ectodomain; (4) expansion of uncleaved Spike protein in the virion particles; (5) increment of Spike concentration per virion particles; and (6) evasion of the immune system. These factors play key roles in the fast spreading of SARS-CoV-2 variants of concern, including the Omicron.

A substantial number of humans are at risk for infection by vector-borne flaviviruses, resulting in considerable morbidity and mortality worldwide. These viruses also infect wildlife at a considerable rate, persistently cycling between either the tick or mosquito vector to small mammals (e.g. rodents, skunks) and reptiles to non-human primates and humans. Substantially increasing evidence of viral persistence in wildlife continue to be reported. In addition to in humans, viral persistence can also be established in mammalian, reptile, arachnid, and mosquito systems, as well as insect cell lines in culture. Although a considerable amount of research has focused on the potential roles of defective virus particles, autophagy and/or apoptosis induced evasion of the immune response, the precise mechanism of flavivirus has yet to be elucidated. In this review, we present findings that aid in further understanding of how vector-borne flavivirus persistence is established in wildlife. Research studies to be discussed include determining the critical roles universal flavivirus non-structural proteins played in viral persistence, the development of relevant animal models of viral persistence, and investigating the host responses that allow vector-borne flavivirus replication without destructive effects on infected cells. These findings underscore the viral–host relationships in wildlife animals and could be used to elucidate the mechanisms for the establishment of viral persistence in these animals.

Viral infections induce exosomes containing viral material and inflammatory factors. During respiratory tract infection, exosomes can easily cross the blood-brain barrier and transmit the inflammatory signal to the brain; however, such a hypothesis has no experimental evidence. The study investigated whether exosomes from virus mimetic poly (I:C)-primed airway cells enter the brain and interact with brain immune cells microglia. Airway cells were isolated from Wistar rats and BALB/c mice; microglial cell cultures - from Wistar rats. Exosomes from poly (I:C)-stimulated airway cell culture medium were isolated by precipitation, visualised by transmission electron microscopy, and evaluated by nanoparticle analyser; exosomal markers CD81 and CD9 were determined by ELISA. For in vitro and in vivo tracking, exosomes were loaded with Alexa Fluor 555-labelled RNA. Intracellular reactive oxygen species (ROS) were evaluated by DCFDA fluo-rescence and mitochondrial superoxide - by MitoSOX. The exosomes from poly (I:C)-primed airway cells entered the brain within an hour after intranasal introduction, were internalised by microglia, and induced intracellular and intramitochondrial ROS production. There was no ROS increase in microglial cells was after treatment with exosomes from airway cells untreated with poly (I:C). The data indicate that virus-primed airway cell exosomes might enter the brain and induce the activation of microglial cells.

All neurological diseases have their pathological progress influenced by microglial cells, which react to insults with multiple morphofunctional phenotypes. However, the complete morphological spectrum of the reactive microglia, revealed by the three-dimensional microscopic reconstruction, has not been explored in detail in virus limbic encephalitis. Here, we used anatomical series of brain sections from a previous study using Piry arbovirus encephalitis, expanding the original investigation to CA1/CA2. The morphological response of the homeostatic and reactive microglia was investigated 8 days after infection. The hierarchical cluster and linear discriminant function analysis of multimodal morphometric features allowed to distinguish between the microglial morphology of infected individuals and controls. In order to represent more broadly the morphological spectrum of the microglia of each cluster, representative cells of the homeostatic and reactive microglia were chosen, using the sum of the distances of each cell in relation to all the others. Overall, the multivariate statistical analysis showed that the reactive microglia of infected animals have more complex trees and thicker branches, that cover a larger volume of tissue than the microglia of control animals. With this approach a more reliable representation of the microglia dispersion in the Euclidean space, would be closer to the spectrum of morphotypes of the control and infected groups, and help to avoid hiding the morphological kaleidoscope of surveillant and reactive microglia. As form precedes function in nature, our findings are a good starting point for future research with integrative approaches to microglia form and function.

All neurological diseases have their pathological progress influenced by microglial cells, which react to insults with multiple morphofunctional phenotypes. However, the complete morphological spectrum of the reactive microglia, revealed by the three-dimensional microscopic reconstruction, has not been explored in detail in virus limbic encephalitis. Here, we used anatomical series of brain sections from a previous study using Piry arbovirus encephalitis, expanding the original investigation to CA1/CA2. The morphological response of the homeostatic and reactive microglia was investigated 8 days after infection. The hierarchical cluster and linear discriminant function analysis of multimodal morphometric features allowed to distinguish between the microglial morphology of infected individuals and controls. In order to represent more broadly the morphological spectrum of the microglia of each cluster, representative cells of the homeostatic and reactive microglia were chosen, using the sum of the distances of each cell in relation to all the others. Overall, the multivariate statistical analysis showed that the reactive microglia of infected animals have more complex trees and thicker branches, that cover a larger volume of tissue than the microglia of control animals. With this approach a more reliable representation of the microglia dispersion in the Euclidean space, would be closer to the spectrum of morphotypes of the control and infected groups, and help to avoid hiding the morphological kaleidoscope of surveillant and reactive microglia. As form precedes function in nature, our findings are a good starting point for future research with integrative approaches to microglia form and function.

The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes mellitus, hypertension and obesity.

With the outbreak of the COVID-19 disease, the research community is producing unprecedented efforts dedicated to better understand and mitigate the affects of the pandemic. In this context, we review the data integration efforts required for accessing and searching genome sequences and metadata of SARS-CoV2, the virus responsible for the COVID-19 disease, which have been deposited into the most important repositories of viral sequences. Organizations that were already present in the virus domain are now dedicating special interest to the emergence of COVID-19 pandemics, by emphasizing specific SARS-CoV2 data and services. At the same time, novel organizations and resources were born in this critical period to serve specifically the purposes of COVID-19 mitigation, while setting the research ground for contrasting possible future pandemics. Accessibility and integration of viral sequence data, possibly in conjunction with the human host genotype and clinical data, are paramount to better understand the COVID-19 disease and mitigate its effects.

The coronavirus pandemic will deeply affect the tourism and travel sector. It is already clear now that its economic impact would be more severe that in the case of the Severe Acute Respiratory Syndrome (SARS) in 2002-2003. Although not as deadly as SARS, coronavirus infection has a longer incubation period and leaves about 85% of the infected without any (or with just mild) symptoms which makes it more difficult to track and to contain. Moreover, it appears to be much more contagious than its predecessor. The goods news is that most people recover from the disease and develop antibodies that can protect them from getting infected again (natural vaccination). Those cured might become the key element for the post-virus recovery strategies of tourism organisations. People with the acquired immunity to the virus would be capable of travelling freely without spreading the disease. Airlines, hotels and gastronomy should aim at this group offering them discounts and special offers. However, the problem is how to effectively ensure that everyone who claims to be cured from COVID-19 is telling the truth. Health tracking bracelets, apps, and other advanced technological solutions should be put in place. Recent best practices from Hong Kong, mainland China, or India might be applied.

The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.

Autophagy is an evolutionarily conserved central process in host metabolism. Among its major functions are conservation of energy during starvation, recycling organelles, and turnover of long-lived proteins. Besides, autophagy plays a critical role in removing intracellular pathogens and very likely represents a primordial intrinsic cellular defence mechanism. More recent findings indicate that it has not only retained its ability to degrade intracellular pathogens, but also functions to augment and fine tune antiviral immune responses. Interestingly, viruses have also co-evolved strategies to manipulate this pathway and use it to their advantage. Particularly intriguing is infection-dependent activation of autophagy with positive stranded (+)RNA virus infections, which benefit from the pathway without succumbing to lysosomal degradation. In this review we summarise recent data on viral manipulation of autophagy, with a particular emphasis on +RNA viruses and highlight key unanswered questions in the field that we believe merit further attention.

Abstract: Thermostability of vaccines, particularly enveloped viral vectored vaccines, remains a challenge for their delivery wherever needed. Freeze-drying of viral vectored vaccines is a prom-ising approach but remains challenging due to the water removal process from the outer and in-ner parts of the virus. In the case of enveloped viruses, freeze-drying induces increased stresses on the envelope, which often leads to inactivation of the virus. In this study, we design a method to freeze-dry a recombinant Vesicular Stomatitis Virus (VSV) expressing the SARS-CoV-2 spike glycoprotein. Since the envelope of VSV is composed of 50% lipid and 50% protein, the formula-tion study focused on both the protein and lipid portions of the vector. Formulations were pre-pared primarily using sucrose, trehalose, and sorbitol as cryoprotectants; mannitol as a lyopro-tectant; and histidine as a buffer. Initially, the infectivity of rVSV-SARS-CoV-2 and cake stability were investigated at different final moisture contents. High recovery of the infectious viral titer ( 0.5 to 1 log loss) was found at 3-6% moisture content with no deterioration of the freeze-dried cakes. To further minimize infectious viral titer loss, the composition and concentration of the ex-cipients were studied. An increase from 5 to 10% of both cryoprotectants and lyoprotectant, to-gether with the addition of 0.5% gelatin, resulted in the improved recovery of infectious virus titer and stable cake formation. Moreover, the secondary drying temperature of the freeze-drying pro-cess showed a significant impact on the infectivity of rVSV-SARS-CoV-2. The infectivity of the vector declined drastically when the temperature was raised above 20°C. Throughout a long-term stability study, formulations containing 10% sugar (sucrose/trehalose), 10% mannitol, 0.5% gelatin, and 10 mM of histidine showed satisfactory stability for six months at 2-8°C. The development of this freeze-drying process and the optimized formulation minimizes the need for a costly cold chain distribution system.

The plethora of bio-functional compounds present in fermented alcoholic beverages like wine, as well as the valorization of bioactives from their wineries/breweries by-products like grape pomace and grape seed, has gained significant interest in the functional foods sector. Wine has always accompanied humanity, for religion or for health. For example, Christians are using wine in the “Holy Communion”, following what Jesus Christ himself did and said during the Last Supper, while the benefits of the wine consumption in moderation was embedded in all Mediterranean civilizations, as it is mentioned by the wise King-Prophet David in his psalms, but also by Hip-pocrates and other wise men, in a Greek-based philosophy of “All things in Moderation” (Cleobulus of Lindos; 6th century BC). In modern times, and after the outbreak of research on wine benefits since the 90’s, when the term “French Paradox” was introduced in the US public during a CBS show, recent evidence has outlined that these benefits are derived by the synergisms of its bio-functional compounds and their digestion-derived metabolites. Within this article, the proposed health benefits of moderate wine consumption, as a functional component of a balanced diet (i.e. the Mediterra-nean Diet), against inflammation-related chronic disorders, is thoroughly reviewed. The various bio-functional compounds of both wine and wineries’ by-products, such as their bioactive phe-nolics, unsaturated fatty acids, polar lipids, and dietary fibers, and their functional antioxidant, anti-inflammatory and antithrombotic health promoting properties are also thoroughly evaluated. The mechanisms of actions and synergism, by which the health benefits are elicited, are also ex-plored. Functional properties of non-alcoholic wine products are also introduced. Emphasis is also given to applications of wineries’ by-products bioactives, as ingredients of bio-functional foods, supplements and nutraceuticals. Limitations and future perspectives for this popular functional alcoholic beverage (wine) ant its rich in bioactives by-products are also addressed. .

Lactococcus lactis subsp. cremoris C60 is a probiotic strain of lactic acid bacteria (LAB) which induces various immune modifications in myeloid lineage cells. These modifications subsequently reg-ulate T cell function, resulting in enhanced immunity both locally and systemically. Here, we report that C60 suppresses tumor growth by enhancing macrophage function via metabolic al-terations, thereby increasing adenosine triphosphate (ATP) production in a murine melanoma model. Intragastric (i.g.) administration of C60 significantly reduced tumor volume compared to saline administration in mice. The anti-tumor function of intratumor (IT) macrophage was up-regulated in mice administered with C60, as evidenced by an increased inflammatory phenotype (M1) rather than an anti-inflammatory/reparative (M2) phenotype, along with enhanced anti-gen-presenting ability, resulting in increased tumor antigen-specific CD8+ T cells. Through this functional modification, we identified that C60 establishes a glycolysis-dominant metabolism, rather than fatty acid oxidation (FAO), in IT macrophages, leading to increased intracellular ATP levels. To address the question of why orally supplemented C60 exhibits functions in distal places, we found a possibility that bacterial cell wall components, which could be distributed throughout the body from the gut, may induce stimulatory signals in peripheral macrophages via Toll-like receptors (TLRs) signaling activation. Thus, C60 strengthens macrophage anti-tumor immunity by promoting a predominant metabolic shift towards glycolysis upon TLR-mediated stimulation, thereby increasing substantial energy production.

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

A rare neurological condition known as Dyke-Davidoff-Masson syndrome (DDMS) is characterized by cerebral hemiatrophy, facial asymmetry, contralateral motor impairment, and seizures. Cerebral hypoplasia, ventriculomegaly, paranasal sinus hyper-pneumatization, and compensatory osseous expansion are classic imaging findings. The relationship between clinical and neuroimaging findings provides the basis for the diagnosis of DDMS. DDMS is treated with anticonvulsant medication and physical therapy. This is the case of a 26-year-old male, with a known case of cerebral palsy and on antiepileptics for 15 years, who presented with complaints of generalized weakness, vomiting, difficulty walking, recurrent convulsions, and a recent episode of generalized tonic-clonic seizures. Neuroimaging revealed findings significant of Dyke Davidoff Masson Syndrome. Understanding its imaging and clinical characteristics facilitates prompt and precise diagnosis, permitting appropriate management.

Since ancient times, various scientists and doctors have utilized different herbs to heal diseases. Due to the rise in drug resistance and the negative effects of chemosynthetic drugs, researchers and the general public around the world have become more interested in medicinal herbs and plant metabolites/extracts. This is due to its non-toxicity and several health benefits when used to treat diseases in clinical and medical settings. Ocimum basilicum is one such plant, possessing a wide range of bioactive phytochemicals including alkaloids, phenolics, flavonoids, tannins, saponins, reducing sugars, cardiac glycosides, steroids and glycosides, as well as complex pharmacological activities including anti-inflammatory, antifungal, antibacterial, antioxidant, wound healing and antiviral properties. The results of many studies on Ocimum basilicum plant extracts are collected and presented in this review. The plant extracts have an excellent potential to be used as medicinal raw materials and exhibit an extensive variety of therapeutic capacities, including antibacterial, antioxidant, wound healing, anti-inflammatory, antifungal, and antiviral properties.

Inflammation is natural protective response of the body tissue caused by various stimuli. Macrophages start and control the inflammatory response. Microalgae have high value of ingredients including carotenoids which are well known for anti-inflammatory properties and used for various products in functional food industries. A green microalgal, Tetraselmis species contains a various type of carotenoids such as lutein, violaxanthin, astaxanthin, fucoxanthin, α-carotene and β-carotene. Therefore, we studied whether carotenoids isolated from Tetraselmis sp. with different culture conditions in Raw 264.7 cells and zebrafish (Danio rerio) have an anti -inflammatory effect. Carotenoid extracts of natural seawater (NS) and magma seawater (MS) showed inhibitory activity of nitric oxide (NO) overproduction without toxicity. In addition, carotenoid extracts of NS and MS inhibited pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)- 1β and IL-6. Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, which are inflammatory mediators also decreased by pretreatment of NS and MS. Carotenoid extracts of NS and MS pretreatment also reduced phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kB (NF-kB). In conclusion, the carotenoid extract of Tetraselmis sp. has an anti -inflammatory effect and can be potential industrial ingredient.

A series of pyrazolopyrimidines derivatives 4– 11 were synthesized using 1-(6-(3-methoxyphenyl)-4-methylpyridazin-3-yl)-1H-pyrazolo [3,4-d] pyrimidin-4-amine 3 as a starting material. The detailed synthesis, structure assignments of the novel compounds based on chemical and spectroscopic evidence, spectroscopic data, pharmacological properties and molecular docking are reported. The pharmacological evaluation illustrated that many of these compounds have good analgesic, anti-inflammatory and antimicrobial activities.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. Here, I explore the possibility that the accumulation of lipofuscin may to some extent exacerbate every other kind of age-related damage. I do not think that lipofuscin removal will reverse/prevent all forms of aging, just the major component facing us currently. In this piece, I will review what is known about lipofuscin accumulation from evolutionary and mechanistic standpoints and discuss a method of removing it from single cells in vitro.

Hydroxamic acid (HA) derivates displayed antibacterial and antifungal activities. HA with various numbers of carbon atoms (C2, C6, C8, C10, C12 and C17), complexed to different metal ions Fe(II/III), Ni(II), Cu(II) and Zn(II) were evaluated for their antimycobacterial activities and their anti-biofilm activities. Some derivates, among others HA12Fe2, inhibited the development of Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium marinum biofilms and could even attack pre-formed Pseudomonas aeruginosa biofilm. Proteomic profiles showed that the potential targets of HA10FeCl were mainly related to mycobacteria stress adaptation, involving cell wall lipid biosynthesis, drug resistance and tolerance, siderophore metabolism. This study provides new insights regarding the antimycobacterial activities of the HA and their complexes, especially about their potential antibiofilm activities.

Food and drinks can be contaminated with pollutants such as lead and strontium and this poses a serious danger to human health. For this reason, a number of effective sensors have been developed for the rapid and highly selective detection of such contaminants. TBA, a well-known aptamer developed to selectively target and thereby inhibit the protein of clinical interest -thrombin, is receiving increasing attention for sensing applications, particularly for the sensing of different cations. Indeed, TBA, in the presence of these cations, folds into the stable G-quadruplex structure. Furthermore, different cations produce small but significant changes in this structure that result in changes in the electrical responses that TBA can produce. In this article we produce an overview of the expected data regarding the use of TBA in the detection of lead and strontium, calculating the expected electrical response using different measurement techniques. Finally, we conclude that the TBA should perform better as a detector of strontium rather than lead.

Cancer is a catchall term that refers to a collection of more than one chronic disease that can adversely affect the body, including the organs of the body. These diseases can be grouped together under the umbrella term "cancer." Cancer is a catch-all term that is used to refer to a number of different diseases. During the process of looking for new chemical entities, it was found that certain compounds with a basic nucleus of benzoic acid (BA) exhibit a remarkable anticancer potential. This was discovered while the researchers were looking for new chemical entities. In the sixteenth century, the aromatic chemical known as BA, which is also known as an aromatic carboxylic acid, was discovered. BA is also referred to as an aromatic carboxylic acid. When it comes to the chemical synthesis of a wide range of different active molecules, the utilization of a sizeable quantity of BA as a raw material is absolutely necessary. In addition to being present in a variety of other naturally occurring compounds, the BA moiety is the component that is responsible for the activity of the naturally occurring compounds vanillin, gallic acid, and syringic acid. In the synthesis of a wide variety of synthetic bioactive molecules, the BA scaffold is utilized as a building block. The drugs furosemide, bumetanide, benzocaine, tetracaine, and bexarotene are all examples of molecules that fall into this category. The scope of this review article allows for the discussion of a number of noteworthy and recent achievements of BA derivatives in terms of their effectiveness against cancer.

The ethanol extract (EE) prepared from the leaves of Tibouchina granulosa, and its fraction in ethyl acetate (fEA) were evaluated concerning their capacity to reduce inflammation in different experimental models. fEA was also studied concerning its chemical constituents. EE and fEA were assayed for their anti-inflammatory potential, using formalin-induced licking behaviour and carrageenan-induced inflammation into the subcutaneous air pouch (SAP) models. Reduction in polymorphonuclear cells (PMN) activation was performed in freshly isolated PMN. Chromatographic analysis of fEA was done by HPLC. Hispiduloside was isolated as the main constituent in fEA and its quantity was estimated to be 11.75% in fEA, 3.05% in EE, and 0.2% (w/w) in the plant. EE (30 mg/kg) significantly reduced the second phase of formalin-induced licking. fEA demonstrated a reduction in leukocyte migration into the SAP. EE and fEA drastically reduced cytokines (TNF-α, IL-1β, and IFN-γ), nitric oxide (NO) production, in vitro PMN migration induced by C5a and IL-8, and TNF-α and IL-1β gene expression. Taken together our data indicate that either ethanol extract or its fEA fraction from leaves of T. granulosa present an anti-inflammatory effect contributing to the pharmacological and chemical knowledge of this species and confirming the rationale behind its traditional use.

Polysaccharides from marine algae exhibit beneficial biological activities. In this study, we examined the effect of polysaccharides from Codium fragile (PCF) on prebiotic and anti-obesity activity. PCF increases the growth of specific beneficial microbial populations with concomitant decrease in pathogenic microbes. Further, total phenolic content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity (DPPH activity) after fermentation with PCF as carbon source were higher than for the glucose as control. Moreover, PCF inhibited adipocyte differentiation by inducing differentiation-related factors when the induction of 3T3-L1 preadipocytes into adipocytes was induced. Therefore, we suggest that PCF can be used as prebiotic material with anti-obesity for human health.

Diabetes mellitus remains a major risk factor for developing cardiovascular diseases, resulting in increased morbidity and mortality associated with cardiovascular complications. Given the burden of diabetes-related cardiovascular complications, there is a need to identify strategies, safe and effective therapeutic agents that could effectively prevent and control diabetes. Presently, many patients living with diabetes depends on traditional medicines as an alternative cure. Channa striatus (Haruan) is a freshwater fish traditionally used to treat wounds, inflammations, and pains. Several pharmacological investigations have supported the folkloric claims of C. striatus extracts, including hypoglycemic, hypolipidemic, antioxidant, anti-inflammatory, and pro-platelet aggregation activities. The therapeutic potentials of C. striatus were demonstrated to be associated with the presence of high content essential amino acids and good fatty acids known to improve cell growth and facilitate wound healing. Therefore, C. striatus bioactive compounds have great potentials to serve as lead candidates in developing novel therapeutic agents for the management of diabetes and related cardiovascular diseases. This review aims to provide a comprehensive overview of the pharmacological properties and therapeutic potentials of C. striatus for the management of diabetes and associated cardiovascular complications.

Abstract: As a risk factor, obesity is a threat to human well-being and related metabolic disorders such as diabetes mellitus and dyslipidemia. adipogenesis is defined as the proliferation and maturation of adipocyte predecessor cells to adipocyte. As the adipogenesis process decides adipocyte production, it may be considered a therapeutic target for obesity and obesity-related disorders. White adipose tissue abnormal expansion increases the size and number of adipocytes. For that reason, this review aims to spot the molecular mechanisms implicated in adipogenesis that lead to application in the therapeutic targets. Keywords: adipogenesis, signaling pathways, anti-obesity treatment, obesity

Since the financial crisis in 2008, the U.S. economy has weakened, and the world economy has slowly developed. As the world's leading country, the United States has used many methods to restore the economy. But it does work efficiently. However, there are many issues in developed countries such as domestic social, economic, immigration in the United States/United Kingdom; those are not optimistic. Developed countries have entered a dilemma. The neoliberalism financial system has been unable to move forward. Populists have pointed out that those problems have been causing by globalization. Under the leadership of the Brexit Referendum, President Trump has caused a wave of anti-globalization. Under a series of systems such as the China-US trade war and the US-Mexico border wall repairs, the anti-globalization trend is getting stronger. This article mainly analyzes the in-depth reasons and mechanism research of globalization and anti-globalization alternately—the data obtained from an international method performance study. The results show that anti-globalization is temporary, along with globalization. There are three main factors affecting globalization: the situation of the dominant country, natural disasters, and wars. After so much literature review, I believe that the United States' globalization is gradually weakening, and globalization may return to regionalization under the United States' opposition.

Product counterfeiting is an on-going problem in supply chains and retail environments, Recently an anti-counterfeiting protocol to address this issue via cost-effective use of auto-identification technologies such as radio-frequency identification (RFID) was proposed by researchers.Yet the use case of re-selling the same product was not been fully addressed which might cause serious problem for the exciting and proposed schemes and transactions. This paper proposes an extended RFID-based anti-counterfeiting to address the use case of the original buyer reselling the same item to a second buyer. The extended scheme will be followed by a formal security analysis to show that the proposed protocol satisfies the requirements of security correctness and is resistant to compromise through security attacks.

Chaenomeles plants are adapted to diverse ecological zones particularly the temperate areas of Korea, Japan and China. In China, Chaenomeles speciosa mainly planted in Chongqing, Anhui and Hubei provinces. Most of the studies till date have been focused on the anti-inflammatory activities of C. speciosa fractions. The present study aimed to review the maximum literature reported for the presence of various phytochemicals in C. speciosa. In addition, the pharmacological properties of these chemical compounds of this plant shall also be discussed. The extracts of the various parts of the plant are rich in diversity of antioxidants, organic acids, phenolics, terpenoides and many different phytochemicals that bear strong anticancer, antioxidant, anti-viral, antibacterial properties, anti-inflammation, anti-hyperlipidemic, anti-hyperglycemic and anti-parkinson properties. C. speciosa fruits have broad scope in industry as well as in medicines. Not only the leaves and fruits of C. speciosa plant, but various other parts including roots, seeds, bark twigs, and flowers all have long history of clinical trials in curing many human ailments. However, the maximum accessible data concerning the chemical composition and their broad pharmacological properties of C. speciosa plant parts is pretty restricted that make it more appealing for indepth investigations.

Fracking in the UK has yet to reach full industrial development but it is still subject to significant opposition. This study uses Beck’s Risk Society theory and anti-politics to examine the views voiced by opponents to fracking in Yorkshire, England. A qualitative approach was used; local newspaper reports were evaluated alongside semi-structured interviews with protesters to provide a thematic analysis. Although there are signs of post-materialist concerns with the environment these issues did not dominate the discussion. Scientists were not held responsible for the risks involved in fracking. Instead economic greediness of politicians and austerity measures were perceived as putting the environment and people’s health at risk. Interviewees thought fossil fuel energy production was economically advantaged over more sustainable energy and jobs in the low carbon economy. Protesters’ trust in politicians had been eroded but faith in democracy remained. It is suggested a citizen-led deliberative approach to all the concerns raised, not simply those relating to scientific risk, might achieve some level of resolution over fracking in the UK.

Background. Nanotechnology is promising field for generating new applications. A green synthesis of nanoparticles through biological methods using plant extract have a reliable and ecofriendly approach to improve our global environment. Methods. Silver nanoparticles (AgNPs) were synthesized using aqueous extract of Anagalis arvensis L and silver nitrate and were physicochemically characterized. Results. The stability of AgNPs toward acidity, alkalinity, salinity and temperature showed that they remained stable at room temperature for more than two months. The SEM and TEM analysis of the AgNPs showed that they have a uniform spherical shape with an average size in the range of 40–78 nm. Further 1-Dibhenyl-2-Picrylhydrazl radical in Anagalis arvensis L.mediated AgNPs showed a maximum activity of 98% at concentration of 200μg/mL. Hydrogen peroxide scavenging assay in Anagalis arvensis L. mediated AgNPs showed a maximum activity of 85% at concentration of 200μg/mL. Reducing power of Anagalis arvensis L.Ag NPs exhibited a higher activity of 330 μg/mL at concentration of 200 μg/mL. These NPs have cytotoxic effects against brine shrimp (Artemia salina) nauplii with a value of 53% LD 178.04μg/mL. Conclusion. The AgNPs synthesized using Anagalis arvensis L. extract demonstrate a broad range of applications.

Versatile hybrid organic polymers are prepared using two active intermediates such as cynuric chloride and chitosan derivatives. The prepared chalcones are characterized by using FT-IR, UV, and proton NMR, thermal analysis and Minimum inhibitory Concentration. Thermal stability of the synthesized hybrid polymer is found using TGA and the hybrid chitosan derivative chalcone is thermally stable up to 270 °C. The antimicrobial activity of the prepared chitosan containing chalcone moiety are find out using Minimum Inhibitory Concentration (MIC) method. The synthesized versatile chalcone shows excellent antimicrobial activity against gram-negative bacteria such as Pseudomonas aeruginosa; and Gram-positive bacteria Chalcone containing halogen moiety shows high activity (MIC 7.8 µg/mL) than the hydroxyl containing chalcone. Cytotoxicity activity of the synthesized composites shows high activity.

Three new secoiridoid constituents Gonocarin A-C (1-3) and a new derivative Gonocarin A monoacetate (4), along with two known lignins pinoresinol (5) and paulownin (6) were isolated from the seed of Gonocaryum calleryanum (Baill.) Becc. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly mass spectroscopy and 2D NMR (1H–1H COSY, HMQC, HMBC, and NOESY) spectroscopy. When mouse macrophages RAW264.7 were treated with compounds 1-6 together with LPS -stimulated, a concentration-dependent inhibition of nitric oxide (NO) and tumor necrosis factor (TNF-α) productions were detected. The results confirmed that the Gonocaryum calleryanumrrg could be a potential anti-inflammatory agent.

Cordycepin is an extract from the insect fungus Cordyceps. militaris, which is a traditional medicine with various biological function. In previous studies, cordycepin had been reported with excellent anti-obesity effect, but the mechanism is unclear. A large quantity of evidences showed that prolactin plays an important part in body weight regulation, hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin by reducing prolactin release via an adenosine A₁ receptor. In vivo, obese rats model was induced by high fat diet for 5 weeks, the serum and liver lipids coupling with serum prolactin were reduced by treatment of cordycepin, the results suggested that cordycepin is a potential drug for therapying obesity which could be related with prolactin. In vitro, cordycepin could inhibit prolactin secretion in GH₃ cells via upregulating the expression of adenosine A₁ receptor, the inhibition effect could be blocked by an antagonist of adenosine receptor A1 DPDPX, prolactin induced the upregulation of lipogenesis genes PRLR, and P-JAK2 in 3T3-L1 cells. Intriguingly, cordycepin would down-regulate the expression of prolactin receptor (PRLR). Thus, we concluded that cordycepin modulate body weight by reducing prolactin release via an adenosine A₁ receptor.

Oligonol is a low-molecular-weight polyphenol derived from lychee fruit. This study was conducted to examine whether oligonol has an ameliorative effect on diabetes-induced pancreatic damage via oxidative stress-induced inflammation. Oligonol was orally administered at 10 or 20 mg/kg body weight/day for 10 days to streptozotocin-induced diabetic rats, and changes in serum glucose, C-peptide, insulin, reactive oxygen species (ROS), and thiobarbituric acid-reactive substance (TBARS) levels as well as body weight and food and water consumption were assessed. Furthermore, rat pancreases were analyzed for weight, ROS generation, TBARS level, insulin content, and protein expressions of phosphor (p)-p38, p-extracellular-signal regulated kinase 1/2, p-inhibitor of nuclear factor kappa Bα, nuclear factor-kappa Bp65, cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. Markers of diabetes were shown to be decreased by oligonol administration and histological damage in the pancreas was also ameliorated. These results indicate that oligonol exerts antidiabetic activities, which may be mediated via antioxidative, stress-related, anti-inflammatory signaling.

The chemical investigation of the anti-yeast methanol extract from the stem bark of Terminalia mantaly led to the isolation of seven compounds: 3-O-methyl-4-O-α-rhamnopyranoside ellagic acid (1), 3-O-mehylellagic acid (2), arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid (3), arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside (4), 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid (5), stigmasterol (6), stigmasterol 3-O-β-D-glucopyranoside (7). Their structures were established by means of spectroscopic analysis and comparison with published data. Compounds 1-5 were tested in vitro for activity against three pathogenic yeast isolates, Candida albicans, Candida parapsilosis and Candida krusei. The activity of compounds 1, 2 and 4 were comparable to that of the reference compound fluconazole (MIC values below 32 µg/ml) against the three tested yeast isolates. They were also tested for inhibitory properties against four enzymes of metabolic significance: Glucose-6-Phosphate Deshydrogenase (G6PD), human erythrocyte Carbonic anhydrase I and II (hCA I and hCA II), Glutathione S-transferase (GST). Compound 4 showed highly potent inhibitory property against the four tested enzymes with overall IC₅₀ values below 4 µM and inhibitory constant (Ki) <3 µM.

Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p<0.001 and HR 0.77, p<0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p<0.012), with the exception of melanoma (in women, HR 0.80, p=0.006). PFS was longer in men than in women (HR 0.67, p<0.001 and HR 0.77, p=0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs.

During the COVID-19 pandemic, immunosuppressed patients showed prolonged SARS-CoV-2 infections, with several studies reporting the accumulation of mutations in the viral genome. The weakened immune system present in these individuals, along with the effect of antiviral thera-pies, are thought to create a favourable environment for intra-host viral evolution and have been linked to the emergence of new viral variants, which strongly challenged the containment measures and some therapeutic treatments. To assess whether an impaired immunity could lead to an increased instability of viral genomes, longitudinal nasopharyngeal swabs were collected from eight immunocompromised patients and fourteen non-immunocompromised subjects, all undergoing SARS-CoV-2 infection. Intra-host viral evolution was compared between the two groups through deep sequencing, exploiting a probe-based enrichment method to minimize the possibility of artefactual mutations commonly generated in amplicon-based methods, which heavily rely on PCR amplification. Although, as expected, immunocompromised patients expe-rienced significantly longer infections, the acquisition of novel intra-host viral mutations was similar between the two groups. Moreover, a thorough analysis of viral quasispecies showed that the variability of viral populations in the two groups is comparable not only at the consensus level, but also when considering low frequency mutations. This study suggests that a compro-mised immune system alone does not affect SARS-CoV-2 within-host genomic variability.

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.

Artemia (brine shrimp), holds significant value as a live feed for larval fish and crustaceans, owing to their distinctive dietary requirements. However, it is vital to acknowledge that Artemia also carries potential risk as a vector of infection. We conducted a metagenomic analysis to explore the virome present in Artemia cysts collected from inland salt lakes across four distinct regions in Kazakhstan. The study identified the presence of dsDNA phages and RNA virus sequences, with a predominant representation from the Reoviridae, Nodaviridae, Dicistroviridae, Picornaviridae, Astroviridae, Tombusviridae, and Solemoviridae families. In general, this study has significantly enhanced our understanding of the virome of Artemia cysts in the saline lakes of Kazakhstan. It has also furnished crucial insights for the identification, surveillance, and management of viral infections that impact brine shrimp and fish species populations.

The human T-cell leukemia virus type 1 (HTLV-1) is the only known human oncogenic retrovirus. HTLV-1 can cause a cancer called adult T-cell leukemia/lymphoma (ATL). The virus is transmitted through body fluids of infected individuals, primarily breast milk, blood, and semen. At least 5–10 million people in the world are infected with HTLV-1. In addition to ATL, HTLV-1 infection can also cause HTLV-I-associated myelopathy (HAM /TSP). ATL is characterized by low viral ex-pression and poor prognosis. The oncogenesis triggered by HTLV-1 is extremely complex and the molecular mechanisms are not fully understood. However, viral regulatory proteins Tax and HTLV-1 bZIP factor (HBZ) have been shown to play key roles in the transformation of HTLV-1-infected T cells. Moreover, several studies have shown that the final fate of HTLV-1-infected transformed T cell clones is the result of a complex interplay of HTLV-1 oncogenic protein expression with cellular transcription factors that subvert the cell cycle and disrupt reg-ulated cell death, thereby exerting their transforming effects. This review provides updated in-formation on the mechanisms underlying the transforming action of HTLV-1 and the potential therapeutic targets to combat ATL.

In the course of SARS-CoV-2 infection, the 3CL or nsp5 protease plays a pivotal role as the most important viral protease required for the maturation of viral proteins during host infection. Herein, we simulated for 500 ns 3CLproWT, 3CLproH41A, , 3CLproBeta, and 3CLproOmicron, in complex with the substrates nsp 4|5 and nsp 5|6. Our results show that mutations in the 3CLpro present in the SARS-CoV-2 variant of concerns (VOCs) did not lead to significant conformational changes or changes in substrate binding affinities. However, significantly high cleavage rates for the boundary between nsp4 and nsp5 were obtained for 3CLproBeta and 3CLproOmicron and may play a key role in the viral replication and virus fitness gain. Our molecular dynamics data suggest that the cleavage rate of nsp4|5 may be related to the increased amount of viral load observed for these VOCs, releasing more nsp4 than other non-structural proteins. Based on our hydrogen bonding analyses, we also discovered that Gly143 and Glu166 are key residues in substrate recognition, suggesting that these residues may be incorporated as pharmacophoric centers for Beta and Omicron variants in drug design. Our results suggest that Gly143 and Glu166 are essential residues to interact with Gln6 of the different substrates and, therefore, are potential broad-spectrum pharmacophoric centers of SARS-CoV-2 3CLpro.

The risk of the emergence and reemergence of zoonoses is high in regions that are under anthropogenic actions, as they contribute to the risk of vector disease transmission. Yellow fever (YF) is among the main pathogenic arboviral disease in the world, and the Culicidae Aedes albopictus has been proposed to have the potential to transmit yellow fever virus (YFV). This mosquito inhabits both urban and wild environments, and under experimental conditions, it has been shown to be susceptible to infection by YFV. In this study, the vector competence of the mosquito Ae. albopictus for the YFV was investigated. Female Ae. albopictus were exposed to non-human primates (NHP) of the genus Callithrix infected with YFV for blood meal. Subsequently, on the 14th and 21st days post infection, the legs, heads, thorax/abdomen and saliva of the arthropods were collected and analyzed by viral isolation and molecular analysis techniques to verify the infection, dissemination and transmission. The presence of YFV was detected in saliva samples through viral isolation and in the head, thorax/abdomen and legs both by viral isolation and by molecular detection. The susceptibility of Ae. Albopictus to YFV confers a potential risk of reemergence of urban YF in Brazil.

Hashimoto’s thyroiditis (HT) is a common autoimmune disease, with its prevalence rapidly increasing. Both genetic and environmental risk factors contribute to the development of HT. Recently, viral infection has been suggested to act as a trigger of HT by eliciting the host immune response and subsequent autoreactivity. We analyzed features of HT through bioinformatics analysis so as to identify markers of HT development. We accessed public microarray data of HT patients from the Gene Expression Omnibus (GEO) and obtained differentially expressed genes (DEGs) under HT. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed for functional clustering of our protein-protein interaction (PPI) network. Utilizing ranked gene lists, we performed Gene Set Enrichment Analysis (GSEA) using the clusterprofiler R package. By comparing the expression signatures of the huge perturbation database with the queried rank-ordered gene list, connectivity map (CMap) analysis was performed to screen potential therapeutic targets and agents. The gene expression profile of the HT group was in line with general characteristics of HT. Biological processes related to the immune response and viral infection pathways were obtained for the upregulated DEGs. GSEA results revealed activation of autoimmune disease-related pathways and several viral infection pathways. Autoimmune disease and viral infection pathways were highly interconnected by common genes, while the HLA genes which are shared by both were significantly upregulated. CMap analysis suggested that perturbagens, including SRRM1, NLK, and CCDC92, have the potential to reverse the HT expression profile. Several lines of evidence suggested that viral infection and the host immune response are activated during HT. Viral infection is suspected to act as a key trigger of HT by causing autoimmunity. SRRM1, an alternative splicing factor, which responds to viral activity, might serve as potential marker of HT.

Smear-ripened cheeses host complex microbial communities that play a crucial role in the ripening process. Although bacteriophages have been frequently isolated from dairy products, their diversity and ecological role in such type of cheese remain underexplored. In order to fill this gap, the main objective of this study was to isolate and characterize bacteriophages from the rind of a smear-ripened cheese. Thus, viral particles extracted from cheese rind were tested against a collection of bacterial isolates through a spot assay. In total, five virulent bacteriophages infecting Brevibacterium aurantiacum, Glutamicibacter arilaitensis, Leuconostoc falkenbergense and Psychrobacter aquimaris species were obtained. All exhibit a narrow host range, being only able to infect a few cheese-rind isolates within the same species. The complete genome of each phage was sequenced using both Nanopore and Illumina technologies, assembled and annotated. Sequence comparison with known phages revealed that four of them may represent at least new genera. The distribution of the five virulent phages into the dairy-plant environment was also investigated by PCR and three potential reservoirs were identified. This work provides new knowledge on the cheese rind viral community and an overview of the distribution of phages within a cheese factory.

The spreading global sea turtle fibropapillomatosis (FP) epizootic is threatening some of Earth’s ancient reptiles, adding to the plethora of threats faced by these keystone species. Understanding this neoplastic disease, and its likely aetiological pathogen, chelonid alphaherpesvirus 5 (ChHV5), is crucial to understand how the disease impacts sea turtle populations and species and the future trajectory of disease incidence. We generated 20 ChHV5 genomes, from three sea turtle species, to better understand the viral variant diversity and gene evolution of this oncogenic virus. We revealed previously underappreciated genetic diversity within this virus (with an average of 2,035 single nucleotide polymorphisms [SNPs], 1.54% of the ChHV5 genome) and identified genes under the strongest evolutionary pressure. Furthermore, we investigated the phylogeny of ChHV5 at both genome and gene level, confirming the propensity of the virus to be interspecific with related variants able to infect multiple sea turtle species. Finally, we revealed unexpected intra-host diversity, with up to 0.15% of the viral genome varying between ChHV5 genomes isolated from different tumours concurrently arising within the same individual. These findings offer important insights into ChHV5 biology and provide genomic resources for this oncogenic virus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) continues to wreak havoc threatening the public health services and imposing economic collapse worldwide. Tailoring public health responses to the SARS-CoV-2 pandemic depends on understanding the mechanism of viral replication, disease pathogenesis, and accurately identifying acute infections and mapping the spreading risk of hotspots across the globe. However, effective identification and isolation of persons with asymptomatic and mild SARS-CoV-2 infections remain the major obstacles to efforts in controlling the SARS-CoV-2 spread and hence the pandemic. Understanding the mechanism of persistent viral shedding, reinfection, and the post-acute sequalae of SARS-CoV-2 infection (PASC) is crucial in our efforts to combat the pandemic and provide better care and rehabilitation to survivors. Here we present a living literature review on SARS-CoV-2 viral persistence, reinfection and PASC. We also highlight potential areas of research to uncover putative links between viral persistence, intra-host evolution, host immune status, and protective immunity to guide and direct future basic science and clinical research priorities.

The tiered laboratory framework for HIV viral load monitoring accommodates a range of HIV viral load testing platforms, with quality assessment critical to ensure quality patient testing. HIV plasma viral load testing is challenged by the instability of viral RNA. An approach using an RNA stabilizing buffer is described for the Xpert® HIV-1 Viral Load (Cepheid) assay and was tested in remote laboratories in South Africa. EDTA-plasma panels with known HIV viral titres were prepared in PrimeStore molecular transport medium for per-module verification and per-instrument external quality assessment. The panels were transported at ambient temperatures to 13 testing laboratories during 2017 and 2018, tested according to standard procedures and uploaded to a web portal for analysis. A total of 275 quality assessment specimens (57 verification panels and two EQA cycles) were tested. All participating laboratories met study verification criteria (n=171 specimens) with an overall concordance correlation coefficient (ρ_c) of 0.997 (95% confidence interval [CI]: 0.996 to 0.998) and a mean bias of -0.019 log cp/mL (95% CI: -0.044 to 0.063). The overall EQA ρ_c (n=104 specimens) was 0.999 (95% CI: 0.998 to 0.999), with a mean bias of 0.03 log cp/mL (95% CI: 0.02 to 0.05). These panels are suitable for use in quality monitoring of Xpert® HIV-1 VL and are applicable to laboratories in remote settings.

Despite great advances in understanding the dynamics of viral epidemics, the emergence of rapidly spreading, highly pathogenic viruses remains a realistic and catastrophic possibility, which current health systems may not be able to fully contain. An intriguing feature in many recent zoonotic viral outbreaks is the presence of superspreaders, which are infected individuals that cause dramatically more new cases than the average. Here I study the effect of superspreaders on the early dynamics of emerging viruses that have not gained the capacity for efficient human-to-human transmission, i.e viruses with R0 < 1. I show that superspreaders have a higher chance of rapid extinction, but under crowded conditions can lead to outbreaks, causing far more cases than regular viruses. I suggest that outbreaks of highly pathogenic superspreaders are more likely when they coincide in time and space with an unrelated outbreak leading to increased hospital admission rates. These superspreader outbreaks may be difficult to detect, especially in the context of a different epidemic in progress, and can significantly affect mortality patterns observed in affected areas.

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. SARS-CoV-2 nucleic acid, peripheral lymphocyte count, and functionality were assessed. SARS-CoV-2-specific and neutralization antibodies were detected, followed by virus isolation and genome sequencing. The median age of the studied cohort was 59.83±12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. Interferon gamma (IFN-ƴ)-generated CD4+ and CD8+ cells were normal as 24.68±9.60% and 66.41±14.87%. However, the number of IFN-ƴ-generated NK cells diminished (58.03±11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (ID50=157.2, P=0.05). SARS-CoV-2 was not isolated, and a cytopathic effect was lacking. Only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity was observed in COVID-19 patients with long-term SARS-CoV-2 infection.

The integrated stress response (ISR) is an adaptational signaling pathway that is induced in response to different stimuli, such as accumulation of unfolded and misfolded protein, hypoxia, amino acid deprivation, viral infection and ultraviolet light. It has been known that viral infection can activate ISR, but the role of ISR during viral infection is still unclear. In some cases, ISR is a protective mechanism of host cell against infection with virus whilst ISR may be hijacked by viruses for facilitating its replication. In this review, we highlighted recent advances on induction of ISR upon viral infection and the downstream responses involved such as autophagy, apoptosis, formation of stress granules and innate immunity response. We then discussed the molecular mechanism of ISR regulating viral replication and how viruses antagonize this cellular stress response resulting from ISR.

The spread of viral pathogens both between and within hosts is inherently a spatial process. While the spatial aspects of viral spread at the epidemiological level have been increasingly well characterized, the spatial aspects of viral spread within infected hosts are still understudied. Recent experimental studies, however, have started to shed more light on the mechanisms and spatial dynamics of viral spread within hosts. Here, we review these experimental studies as well as the limited number of computational modeling efforts that have begun to integrate spatial considerations for understanding within-host viral spread. We limit our review to influenza virus to highlight key mechanisms affecting spatial aspects of viral spread for pathogens of the respiratory tract. There is considerable empirical evidence for highly spatial within-host spread of influenza virus, yet few computational modeling studies that shed light on possible factors that structure the dynamics of this spatial spread. In existing modeling studies, there is also a striking absence of theoretical expectations of how spatial dynamics may impact the dynamics of viral populations. To mitigate this, we turn to the extensive ecological and evolutionary literature to provide informed theoretical expectations for what viral and host factors may impact the spatial patterns of within-host viral dynamics and for how spatial spread will affect the genetic composition of within-host viral populations. We end by discussing current knowledge gaps related to the spatial component of within-host influenza virus spread and the potential for within-host spatial considerations to inform the development of disease control strategies.

Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. The lncRNAs allow the virus to escape cytosolic surveillance, sequester and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.

Fetuses of pregnant women affected by anti-Ro/anti La antibodies are at risk to develop complete atrioventricular heart block (CAVB) and other potentially life-threatening cardiac affections. CAVB can develop in less than 24 hours. Treatment with anti-inflammatory drugs and immuno-globulins (IVIG) can restore normal rhythm if applied in the transition period. Routine weekly echocardiography as often recommended will seldomly detect emergent AVB. Surveillance of these pregnancies is controversial. To obtain an overview of the current practice in Germany we have developed a web-based survey sent by the DEGUM (German Society of Ultrasound in Med-icine) to ultrasound specialists. Home-monitoring by hand-held Doppler is a promising new approach. With the intention to evaluate practicability, we instructed pregnant women at risk to use hand-held Doppler in the vulnerable period between 18-26 weeks at our university center.

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) antibodies, have initiated a new era in the treatment of malignant melanoma. ICIs can be used in various settings, including as first-line, adjuvant, and neoadjuvant therapy. In the scope of this review, we examined clinical studies utilizing ICIs in the context of treating oral mucosal melanoma, a rare disease albeit with an extremely poor prognosis, with a specific focus on unraveling the intricate web of resistance mechanisms. The absence of a comprehensive review focusing on ICIs in oral mucosal melanoma is notable. Therefore, this review seeks to address this deficiency by offering a novel and thorough analysis of the current status, potential resistance mechanisms, and future prospects of applying ICIs specifically to oral malignant melanoma. Clarifying and thoroughly understanding these mechanisms will facilitate the advancement of effective therapeutic approaches and enhance the prospects for patients suffering from oral mucosal melanoma.

Lung cancer is the leading cause of cancer death worldwide therefore studies about the etiological factors and carcinogenesis are important.The aim of the study is to detect the presence and types of Human papilloma virus (HPV) in lung cancer and non-tumoral lung and Epidermal Growth Factor Receptor (EGFR) mutation prevalance in lung cancer with Polymerase Chain Reaction (PCR) method.Fifty patients who were histopathologically diagnosed lung cancer and 7 patients with non-neoplastic lung disease were enrolled in the study. HPV positivity was detected in 75.4% of the patients. The rate of high-risk HPV positivity was 100% in adenocarcinomas, 64.5% in squamous cell carcinomas, and 57% in non-neoplastic lung. HPV 51 was the most frequent type followed by HPV 16 (43.9%). There was no statistically significant relationship between HPV infection and age, gender and smoking history and EGFR mutation. The prevalence of HPV positivity is variable in lung cancer in different studies and this may be due to many factors including HPV detection methods, number of patients, geographic regions. New studies about the role of HPV infection need to be performed in order to obtain information about the use of prophylactic and theurepatic agents in lung cancer.

To analyze the viral titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) at the anterior nasal site (ANS) and nasopharyngeal site (NS), evaluate their virological dynamics, and validate the usefulness of a newly developed two antigen-detecting rapid antigen diagnostic test (Ag-RDT) that simultaneously detects SARS-CoV-2 and RSV using clinical specimens. This study included 195 asymptomatic to severely ill patients. Overall, 668 specimens were collected simultaneously from the ANS and NS. The cycle threshold (Ct) values calculated from real-time polymerase chain reaction were used to analyze temporal changes in viral load and evaluate the sensitivity and specificity of the Ag-RDT. The mean Ct values for SARS-CoV-2-positive, ANS, and NS specimens were 28.8, 28.9, and 28.7, respectively. The mean Ct values for RSV-positive, ANS, and NS specimens were 28.7, 28.8, and 28.6, respectively. SARS-CoV-2 and RSV showed the same trend in viral load, although the viral load of NS was higher than that of ANS. The sensitivity and specificity of the newly developed Ag-RDT were excellent in specimens collected up to 10 days after the onset of SARS-CoV-2 infection and up to 6 days after the onset of RSV infection.

The emergence of new SARSCoV-2 variants can affect vaccine efficacy, laboratory diagnosis and therapies already available, triggering interest in the search for antiviral agents for SARSCoV-2 infections. Ribavirin (RBV) is a broad-spectrum antiviral with demonstrated in vitro activity against multiple viruses, including SARSCoV-2. Methods. This retrospective study evaluated the dynamic and viral clearance of SARSCoV-2 in hospitalized adult participants (PTs) with COVID-19 pneumonia who received RBV aerosol within a compassionate use study. Was also assessed the impact of RBV on the clinical outcome and the mutational profile of SARSCoV-2. Results. The median RNA values measured in nine PTs included in the study de-creased from baseline to discharge (at BL, threshold cycle (Ct)=22.4, IQR 19.84-5.07; at discharge, Ct=27.92, IQR 26.43-36.11). Seven/9 PTs experienced a clinical improvement, while two PTs deceased during hos-pitalization. In PTs with a favorable outcome the virus clearance rate at discharge was 28.6%. The cumulative clearance rate was 71.4% within day 14th from discharge. A mutational pattern after RBV was detected in 3/5 PTs in whom was available whole genome sequencing. Conclusions. RBV may limit SARSCOV-2 replication resulting in a favorable clinical outcome. Ribavirin may also contribute to the mutational spectrum of SARSCoV-2.

Newcastle disease (ND) is a highly contagious and usually causes severe illness that affects Aves all over the world, including domestic poultry. Depending on the virus's virulence, it can impact the nervous, respiratory, and digestive systems and causes up to 100% mortality. The chIFITM genes are activated in response to viral infection. The current study was conducted to quantify the mRNA of chIFITM genes in vitro in response to ND viral infection. It also examined its ability to inhibit ND virus replication in Chicken Embryo Fibroblast (CEF) cells of Aseel and Kadaknath breeds. Results from the study showed that the expression of all chIFITM genes was significantly upregulated throughout the period in the infected CEF cells of both breeds compared to uninfected CEF cells. In CEF cells of the Kadaknath breed, elevated levels of expression of the chIFITM3 gene dramatically reduced the ND viral growth and the viral load was 60% lower than in CEF cells of the Aseel breed. The expression level of the chIFITMs in Kadaknath ranged from 2.39 to 11.68 log2 folds higher than that of control CEFs, and was consistently (p<0.01) higher than Aseel CEFs. Similar to this, IFN-γ gene expresses strongly quickly and peaks at 13.9 log2 fold at 48 hpi. The result suggests that the Kadaknath chicken breed may have a higher level of disease tolerance compared to the Aseel chicken.

In recent years, given the enormous competition for new products and services, many companies have begun to behave more creatively in an aim to be the best in the market. “Guerrilla marketing” refers to an advertising technique that uses unconventional and cost-effective approaches, employing a variety of strategies that reduce costs. Since the emergence of this concept in the second half of the last century, substantial research has looked into its application and usefulness. This study presents a systematic survey of the field of marketing and advertising: by analyzing the main scientific publications on guerrilla marketing through content analysis in the Web of Science, Scopus, and EBSCO databases. One hundred and sixty-four articles were analyzed in depth and divided into two separate lists: one with publications corresponding to Hutter and Hoffmann’s first classification, and another corresponding to the new variables that emerged from the in-depth study that was carried out. As a consequence, a new taxonomy is proposed for the field, based on the identification of some novel variables characterizing the different existing approaches.

The SARS–CoV-2 infection has caused both acute and chronic COVID–19 disease during the recent pandemic with emerging more transmissible SARS–CoV–2 Omicron variants (BQ1 and XBB1) that have increased demands for more effective immunogens and therapeutic approaches to protect the lives of numerous SARS–CoV-2 affected individuals and reduce overall disease burden that could be affected by concurrent other pathogens causing diseases. Following a worldwide campaign of mass vaccination, there is still a significant demand to quell the harmful effects of novel SARS–CoV–2 infections due to higher mutation rates within specific areas of the SARS–CoV-2 domain, leading to enhanced viral entry, especially within individuals with one or more significant comorbidities, and there is still a dilemma of how prevention of future pandemics will occur as within host animal mutations and cross species transfer naturally occurs. Concerns intersect at a specific point; a gained evolutionary ability of several viruses over the previous centuries to remain undetected during the first stages of infection by means of capping the 5' end of their DNA and RNA genes respectively. This may occur by reducing the rate of host Type I and Type III Interferons (IFN) cellular synthesis, that would usually occur and affect both apoptotic pathways, that facilitate viral replication and clearance, as well as immune cells, that process and present pathogenic antigen epitopes. Furthermore, although methods of vaccination exist, other methods in clinical development remain that could evoke an immune response in different cellular, serum or mucosal compartments being cellular, serum and mucosal that evoke differential antibody responses. Antibodies are classed as natural and synthetic. Natural antibodies are further classified into neutralizing and non-neutralizing, whilst synthetic antibodies are also further classified into monoclonal and polyclonal. As a result of single cell study transcriptome research, viruses do utilize an array of protein receptors for receptor-mediated cellular entry. This, therefore suggests that potential differential production of antibody immunoglobulins (Ig) within serum and mucosal areas remains affected by cytokines, adhesion molecules and chemokines that can be upregulated or downregulated upon host viral infection. Serum plasma antibodies can be multimeric that may not efficiently cross the nasal epithelium cell layer, therefore offering less protection against mucosal inflammation due to mucin proteins. On the other hand, antibodies produced by mucosal plasma cells at epithelial surfaces are known to provide effective immune responses in some viral infections. The existence of developments that stimulate mucosal immune responses has so far only been seen with influenza nasal immunogens. Nevertheless, scientists developed ways of immunization and early treatment worldwide that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration. For example, the administration of human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can stimulate cellular activity to train the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Recently, it was discovered that specific plants secrete proteins that also stimulate the production of Type I Interferons. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. Naturally-selected polymorphic viruses through genetic recombination pose challenges to traditional concepts of cellular and molecular immune system neutralization of these viruses during the first stages of cellular infection. It is until the scientific community realizes this potentially crucial aspect that we will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently monkeypox. Type I IFNs tend to be produced faster than Type III IFNs, and the first induce slightly more abundant pro-inflammatory signals than the latter, meaning that type III IFNs, if produced early, may further decrease the extent of excessive proinflammatory signals. Hence, we believe that nasal sprays containing a low dosage of Type I and Type III IFNs not only represent a relevant COVID-19 therapeutic, but also a potential unknown modulatory therapy of the future. Of note, it has been indicated that IFN I and / or III display significant immunizing and early therapeutic effects for other viral evoked diseases like Influenza (Influenza (A)H1N1), rabies (Rabies lyssavirus), measles (Measles virus), rubella (Rubivirus rubellae), Hepatitis B, HIV-induced AIDS, Ebola, Marburg, as well as bacterial diseases, such as lower respiratory tract infectious diseases induced by Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus, and a number of oncological diseases, like hepatic melanoma.

Among all economically important plant species in the world, grapevine (Vitis vinifera L.) is the most cultivated fruit plant. It has a significant impact on the economies of many countries through wine and fresh and dried fruit production. In recent years, the grape and wine industry has been facing outbreaks of known and emerging viral diseases across the world. Although high-throughput sequencing (HTS) has been used extensively in grapevine virology, the application and potential of third-generation sequencing have not been explored in understanding grapevine viruses and their impact on the grapevine. Nanopore sequencing, a third-generation technology, can be used for direct sequencing of both RNA and DNA with minimal infrastructure. Compared to other HTS methods, the MinION nanopore platform is faster and more cost-effective and allows for long-read sequencing. Due to the size of the MinION device, it can be easily carried for field viral disease surveillance. This review article discusses grapevine viruses and their diagnostic methods, the principle of nanopore sequencing technology and its application in grapevine virus detection, virus–plant interactions, as well as the characterization of viral RNA modifications.

Outbreaks of Ebola ebolavirus (EBOV) have been associated with high morbidity and mortality. Milestones have been reached recently in the management of EBOV disease (EVD) with licensure of an EBOV vaccine and two monoclonal antibody therapies. However, neither vaccines nor therapies are available for other disease-causing filoviruses. In preparation for such outbreaks, and for more facile and cost-effective management of EVD, we seek a cocktail containing orally available and room temperature stable drugs with strong activity against multiple filoviruses. We previously showed that (bepridil + sertraline) and (sertraline + toremifene) synergistically suppress EBOV in cell cultures. Here we describe steps towards testing these combinations in a mouse model of EVD. We identified a vehicle suitable for oral delivery of the component drugs and determined that, thus formulated the drugs are equally active against EBOV as preparations in DMSO, and they maintain activity upon storage in solution for up to seven days. Pharmacokinetic (PK) studies indicated that the drugs in the oral delivery vehicle are well tolerated in mice at the highest doses tested. Collectively the data support advancement of these combinations to tests for synergy in a mouse model of EVD. Moreover, mathematical modeling based on human oral PK projects that the combinations would be more active in humans than their component single drugs.

The development of 3D cerebral brain organoids which accurately resemble aspects of the human brain permits a more accurate characterization of physiological processes and neurological diseases. Cerebral organoids can be grown from stem cell lines with various genetic backgrounds allowing multiple neurodegenerative diseases to be modeled. While dysfunction in neurotransmission of patients with neurodegenerative diseases is expected, the impact of chronic neurodegeneration on the response to viral infection of the CNS is poorly understood. For instance, several mosquito-borne viruses like Dengue virus and West Nile Virus cause post-viral parkinsonism. How CNS infection might impact a host with inherent CNS dysfunction such as Parkinson’s Disease in poorly understood. This preliminary, observational study aimed to understand dysfunction in intrinsic and innate expression of a patient with a neurodegenerative disease and a non-affected individual in relation to potential viral infection in the CNS. Cerebral organoids were generated from human induced pluripotent stem cells with a normal genetic background or with idiopathic Parkinson’s Disease. After differentiation and maturation, organoid size, gene expression and immunofluorescence were evaluated to assess neurotransmission and innate immunity. While there was no significant difference in size of the organoids with a normal or Parkinson’s genetic background, gene expression studies identified multiple differences in innate immunity and neurotransmission. Immunofluorescence also identified differences in protein expression related to neurotransmission and innate immunity. Of note, organoids derived from a Parkinson’s patient exhibited endogenous up-regulation of dopamine and muscarinic acetylcholine receptors, GABA, glycine, and glutamate targets, and the majority of cytokines. This expression pattern suggests a chronic state of neuroexcitation and neuroinflammation in this population of organoids.

ABSTRACT: A woman in her 50s showed symptoms of fever, loss of appetite, vomiting, and general fatigue 2 days after she was bitten by a sick cat, which had later died, in Yamaguchi prefecture, western Japan, in June 2016. She subsequently died of multiorgan failure, and an autopsy was performed to determine the cause of death. However, the etiological pathogens were not quickly identified. The pathological features of the patient were retrospectively re-examined, and the pathology of the regional lymph node at the site of the cat bite was found to show necrotizing lymphadenitis with hemophagocytosis. The pathological features were noticed to be similar to those of patients reported to have severe fever with thrombocytopenia syndrome (SFTS). Therefore, the lymph node section was retrospectively tested immunohistochemically for SFTSV antigen, which revealed the presence of SFTSV antigen. The sick cat also showed similar symptoms and laboratory findings similar to those shown in human SFTS cases. It is highly possible that the patient was infected with SFTSV through the sick cat’s bite. If a patient gets sick in an SFTS-endemic region after a cat bite, SFTS should be considered in the differential diagnosis.