Towards an actionable One Health approach.

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

Alkaloids as drug leads in Alzheimer's treatment: Mechanistic and therapeutic insights.

Alzheimer's disease (AD) has few effective treatment options and continues to be a major global health concern. AD is a neurodegenerative disease that typically affects elderly people. Alkaloids have potential sources for novel drug discovery due to their diverse chemical structures and pharmacological activities. Alkaloids, natural products with heterocyclic nitrogen-containing structures, are considered potential treatments for AD. This review explores the neuroprotective properties of alkaloids in AD, focusing on their ability to regulate pathways such as amyloid-beta aggregation, oxidative stress, synaptic dysfunction, tau hyperphosphorylation, and neuroinflammation. The FDA has approved alkaloids such as acetylcholinesterase inhibitors like galantamine and rivastigmine. This article explores AD's origins, current market medications, and clinical applications of alkaloids in AD therapy. This review explores the development of alkaloid-based drugs for AD, focusing on pharmacokinetics, blood-brain barrier penetration, and potential adverse effects. Future research should focus on the clinical evaluation of promising alkaloids, developing recently discovered alkaloids, and the ongoing search for novel alkaloids for medical treatment. A pharmaceutical option containing an alkaloid may potentially slow down the progression of AD while enhancing its symptoms. This review highlights the potential of alkaloids as valuable drug leads in treating AD, providing a comprehensive understanding of their mechanisms of action and therapeutic implications.

Structural and sequence analysis of the RPO30 gene of sheeppox and goatpox viruses from India.

Sheeppox and goatpox are transboundary viral diseases of sheep and goats that cause significant economic losses to small and marginal farmers worldwide, including India. Members of the genus Capripoxvirus (CaPV), namely Sheeppox virus (SPPV), Goatpox virus (GTPV), and Lumpy skin disease virus (LSDV), are antigenically similar, and species differentiation can only be accomplished using molecular approaches. The present study aimed to understand the molecular epidemiology and host specificity of SPPV and GTPV circulating in India through sequencing and structural analysis of the RNA polymerase subunit-30 kDa (RPO30) gene. A total of 29 field isolates from sheep (n = 19) and goats (n = 10) belonging to different geographical regions of India during the period: Year 2015 to 2023, were analyzed based on the sequence and structure of the full-length RPO30 gene/protein. Phylogenetically, all the CaPV isolates were separated into three major clusters: SPPV, GTPV, and LSDV. Multiple sequence alignment revealed a highly conserved RPO30 gene, with a stretch of 21 nucleotide deletion in all SPPV isolates. Additionally, the RPO30 gene of the Indian SPPV and GTPV isolates possessed several species-specific conserved signature residues/motifs that could act as genotyping markers. Secondary structure analysis of the RPO30 protein showed four α-helices, two loops, and three turns, similar to that of the E4L protein of vaccinia virus (VACV). All the isolates in the present study exhibited host preferences across different states of India. Therefore, in order to protect vulnerable small ruminants from poxviral infections, it is recommended to take into consideration a homologous vaccination strategy.

Intriguing insight into unanswered questions about Mpox: exploring health policy implications and considerations.

The 2022 multi-country Monkeypox (Mpox) outbreak has added concerns to scientific research. However, unanswered questions about the disease remain. These unanswered questions lie in different aspects, such as transmission, the affected community, clinical presentations, infection and prevention control and treatment and vaccination. It is imperative to address these issues to stop the spread and transmission of disease. We documented unanswered questions with Mpox and offered suggestions that could help put health policy into practice. One of those questions is why gay, bisexual or other men who have sex with men (gbMSM) are the most affected community, underscoring the importance of prioritizing this community regarding treatment, vaccination and post-exposure prophylaxis. In addition, destigmatizing gbMSM and implementing community-based gbMSM consultation and action alongside ethical surveillance can facilitate other preventive measures such as ring vaccination to curb disease transmission and track vaccine efficacy. Relevant to that, vaccine and drug side effects have implied the questionability of their use and stimulated the importance of health policy development regarding expanded access and off-label use, expressing the need for safe drug and vaccine development manufacturing. The possibility of reverse zoonotic has also been raised, thus indicating the requirement to screen not only humans, but also their related animals to understand the real magnitude of reverse zoonosis and its potential risks. Implementing infection prevention and control measures to stop the virus circulation at the human-animal interface that includes One Health approach is essential.

Thermoresponsive and Injectable Pluronic F127 Hydrogel for Loading Adipose-Derived Mesenchymal Stem Cells.

BACKGROUND: Stem cell-based therapies display immense potential in regenerative medicine, highlighting the crucial significance of devising efficient delivery methods. This study centers on a pioneering approach that utilizes Pluronic F127 (PF127) as a thermoresponsive and injectable hydrogel designed for the encapsulation of adipose-derived mesenchymal stem cells (AdMSCs). METHODS: The degradation profile, gelation time, and microstructure of the PF127 hydrogel were thoroughly examined. AdMSCs were isolated, expanded, and characterized based on their multi-lineage differentiation potential. AdMSCs from the third passage were specifically employed for encapsulation within the PF127 hydrogel. Subsequently, the cytotoxicity of the AdMSC-loaded PF127 hydrogel was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis assays. RESULTS: Characterized by scanning electron microscopy (SEM), the PF127 hydrogel exhibited a porous structure, indicating its suitability for accommodating AdMSCs and facilitating wound healing. The PF127 hydrogel demonstrated reversible phase transitions, rendering it suitable for in vivo applications. Studies on the gelation time of PF127 hydrogel unveiled a concentration-dependent decrease in gelation time, offering adaptability for diverse medical applications. Analysis of the degradation profile showcased a seven-day degradation period, leading to the decision for weekly topical applications. Cytotoxicity assessments confirmed that AdMSCs loaded into the PF127 hydrogel maintained heightened metabolic activity for up to one week, affirming the safety and appropriateness of the PF127 hydrogel for encapsulating cellular therapeutics. Furthermore, cell apoptosis assays consistently indicated low rates of apoptosis, emphasizing the viability and robust health of AdMSCs when delivered within the hydrogel. CONCLUSIONS: These findings underscore the vast potential of PF127 hydrogel as a versatile and biocompatible delivery system for AdMSCs in the realm of regenerative medicine. Boasting adjustable gelation properties and a remarkable capacity for cell encapsulation, this pioneering delivery system presents a promising path for applications in tissue engineering and wound healing. Ultimately, these advancements propel and elevate the landscape of regenerative medicine.

Current paradigms in employing self-assembled structures: Drug delivery implications with improved therapeutic potential.

Recent efforts have focused on developing improved drug delivery systems with enhanced therapeutic efficacy and minimal side effects. Micelles, self-assembled from amphiphilic block copolymers in aqueous solutions, have gained considerable attention for drug delivery. However, there is a need to further enhance their efficiency. These micelles offer benefits like biodegradability, biocompatibility, sustained drug release, and improved patient compliance. Yet, researchers must address stability issues and reduce toxicity. Nanoscale self-assembled structures have shown promise as efficient drug carriers, offering an alternative to conventional methods. Fine-tuning at the monomeric and molecular levels, along with structural modifications, is crucial for optimal drug release profiles. Various strategies, such as entrapping hydrophobic drugs and using polyethylene oxide diblock copolymer micelles to resist protein adsorption and cellular adhesion, protect the hydrophobic core from degradation. The polyethylene oxide corona also provides stealth properties, prolonging blood circulation for extended drug administration. Amphiphilic copolymers are attractive for drug delivery due to their adjustable properties, allowing control over micelle size and morphology. Emerging tools promise complex and multifunctional platforms. This article summarizes about the challenges as far as the use of micelles is concerned, including optimizing performance, rigorous pre-clinical and clinical research, and suggests further improvement for drug delivery efficacy.

The role of digital health in revolutionizing healthcare delivery and improving health outcomes in conflict zones.

The provision and planning for healthcare delivery in conflict is a pressing imperative. Healthcare within these environments is naturally complex, given the entanglement of affected populations, militaries and oft-deteriorating public services. The field of digital health, placed at the intersection of healthcare and technology, has the power to revolutionize healthcare delivery and improve health outcomes worldwide. Its impact is particularly significant in conflict zones, where it can address the unique challenges faced by these regions. Violence, damaged infrastructure, restricted mobility, forced migration, and overstretched healthcare facilities are all hallmarks of conflict zones that demand novel approaches to addressing them. Health care delivery is being revolutionized by the introduction of digital health technology in conflict zones, which are improving access, emergency response capacities, health information management, and mental health assistance. Doctors and aid organizations can more easily overcome challenges and reach out to underserved populations in these regions because to digital technological improvements. Recent decades have seen a shift in the nature of conflict, and with it, a corresponding shift in the range of digital health solutions available to address geographical, epidemiological, and clinical gaps. The purpose of this letter is to inquire into the application of digital health in conflict zones and its potential to lessen the pressing healthcare needs of affected communities.

Tularemia - a re-emerging disease with growing concern.

Tularemia caused by Gram-negative, coccobacillus bacterium, Francisella tularensis, is a highly infectious zoonotic disease. Human cases have been reported mainly from the United States, Nordic countries like Sweden and Finland, and some European and Asian countries. Naturally, the disease occurs in several vertebrates, particularly lagomorphs. Type A (subspecies tularensis) is more virulent and causes disease mainly in North America; type B (subspecies holarctica) is widespread, while subspecies mediasiatica is present in central Asia. F. tularensis is a possible bioweapon due to its lethality, low infectious dosage, and aerosol transmission. Small mammals like rabbits, hares, and muskrats are primary sources of human infections, but true reservoir of F. tularensis is unknown. Vector-borne tularemia primarily involves ticks and mosquitoes. The bacterial subspecies involved and mode of transmission determine the clinical picture. Early signs are flu-like illnesses that may evolve into different clinical forms of tularemia that may or may not include lymphadenopathy. Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals, oculo-glandular form as a result of conjunctival infection, and oro-pharyngeal form by intake of contaminated food or water. Pulmonary form appears after inhalation of bacteria. Typhoidal form may occur after infection via different routes. Human-to-human transmission has not been known. Diagnosis can be achieved by serology, bacterial culture, and molecular methods. Treatment for tularemia typically entails use of quinolones, tetracyclines, or aminoglycosides. Preventive measures are necessary to avoid infection although difficult to implement. Research is underway for the development of effective live attenuated and subunit vaccines.

France Reports Rise in Severe Neonatal Infections Caused by a New Enterovirus (Echovirus-11) Variant.

The surge in severe neonatal sepsis cases caused by a novel variant of Echovirus 11 (E-11) in France and several European countries has sparked concern. The affected infants, mostly premature and twins, displayed rapid clinical decline within days after birth, presenting symptoms akin to septic shock with hepatic impairment and multi-organ failure. Laboratory findings revealed profound coagulopathy, low platelet counts, and acute renal failure, indicating severe disease progression. Genetic analysis identified a distinct recombinant E-11 lineage, previously unseen in France before July 2022. Despite its novelty, the exact pathogenicity remains uncertain. Although the World Health Organization downplaying immediate public health risks, the absence of a robust global surveillance program hinders accurate prevalence assessment. To mitigate the impact of this novel E-11 variant, establishing robust surveillance, refining diagnostic capabilities, and exploring therapeutic interventions such as intravenous immunoglobulin (IVIg) and pocapavir are imperative for effective management and prevention strategies.

Corrigendum: Association of household fuel with acute respiratory infection (ARI) under-five years children in Bangladesh.

[This corrects the article DOI: 10.3389/fpubh.2022.985445.].

Mechanistic inhibition of gastric cancer-associated bacteria Helicobacter pylori by selected phytocompounds: A new cutting-edge computational approach.

Background: Helicobacter pylori (H. pylori) is a persistent bacterial inhabitant in the stomachs of approximately half the global populace. This bacterium is directly linked to chronic gastritis, leading to a heightened risk of duodenal and gastric ulcer diseases, and is the predominant risk factor for gastric cancer - the second most common cause of cancer-related deaths globally. The increasing prevalence of antibiotic resistance necessitates the exploration of innovative treatment alternatives to mitigate the H. pylori menace. Methods: Initiating our study, we curated a list of thirty phytochemicals based on previous literature and subjected them to molecular docking studies. Subsequently, eight phytocompounds-Glabridin, Isoliquiritin, Sanguinarine, Liquiritin, Glycyrrhetic acid, Beta-carotin, Diosgenin, and Sarsasapogenin-were meticulously chosen based on superior binding scores. These were further subjected to an extensive computational analysis encompassing ADMET profiling, drug-likeness evaluation, principal component analysis (PCA), and molecular dynamic simulations (MDs) in comparison with the conventional drug, Mitomycin. Results: The natural compounds investigated demonstrated superior docking affinities to H. pylori targets compared to the standard Mitomycin. Notably, the phytocompounds Diosgenin and Sarsasapogenin stood out due to their exceptional binding affinities and pharmacokinetic properties, including favorable ADMET profiles. Conclusion: Our comprehensive and technologically-advanced approach showcases the potential of identified phytocompounds as pioneering therapeutic agents against H. pylori-induced gastric malignancies. In light of our promising in silico results, we recommend these natural compounds as potential candidates for advancing H. pylori-targeted drug development. Given their potential, we strongly advocate for subsequent in vitro and in vivo studies to validate their therapeutic efficacy against this formidable gastrointestinal bacterium.

Entropy-Driven, Integrative Bioinformatics Approaches Reveal the Recent Transmission of the Monkeypox Virus from Nigeria to Multiple Non-African Countries.

Monkeypox virus (mpox) has currently affected multiple countries around the globe. This study aims to analyze how the virus spread globally. The study uses entropy-driven bioinformatics in five directions to analyze the 60 full-length complete genomes of mpox. We analyzed the topological entropy distribution of the genomes, principal component analysis (PCA), the dissimilarity matrix, entropy-driven phylogenetics, and genome clustering. The topological entropy distribution showed genome positional entropy. We found five clusters of the mpox genomes through the two PCA, while the three PCA elucidated the clustering events in 3D space. The clustering of genomes was further confirmed through the dissimilarity matrix and phylogenetic analysis which showed the bigger size of Cluster 1 and size similarity between Clusters 2 and 4 as well as Clusters 3 and 5. It corroborated with the phylogenetics of the genomes, where Cluster 1 showed clear segregation from the other four clusters. Finally, the study concluded that the spreading of the mpox is likely to have originated from African countries to the rest of the non-African countries. Overall, the spreading and distribution of the mpox will shed light on its evolution and pathogenicity of the mpox and help to adopt preventive measures to stop the spreading of the virus.

Pathology, virulence-associated gene profiling, antimicrobial susceptibility, and pathogenicity of untypeable capsular serotypes of Pasteurella multocida isolated from slaughtered pigs of India.

Pasteurella multocida is widely distributed in all pig-rearing countries, affecting the economic viability and profitability of pig production. The present research highlights the molecular characterization and pathology of untypeable capsular serotypes of P. multocida in slaughtered pigs from prominent pig-rearing states of India. The prevalence of Pasteurellosis was 27.17% by Pasteurella multocida specific Pasteurella multocida specific PCR (PM-PCR). assay, while isolation rate was 7.62%. The microscopic lesions of bronchopneumonia, tonsillitis, and the presence of bacterial antigens in immunohistochemistry confirmed P. multocida with pathologies. In capsular typing, the majority of the isolates were untypeable with prevalence of 52.15% and 43.58% in molecular and microbiological methods, respectively. All the isolates showed the uniform distribution of virulence genes such as exbB, nanB, sodC, plpB, and oma87 (100%), while the variations were observed in ptfA, hasR, ptfA, pfhA, hsf-1, and plpE genes. The untypeable isolates showed higher prevalence of hsf-1 gene as compared to others. The untypeable serotypes showed a higher degree of resistance to ampicillin, amoxicillin, and penicillin antibiotics. The mouse pathogenicity testing of untypeable capsular isolates confirmed its pathogenic potential. The higher frequency of pathogenic untypeable isolates with antibiotic resistance profile might pose a serious threat to the pigs, and therefore, preventive measures should be adopted for effective control.

Hepatoprotective effects of natural drugs: Current trends, scope, relevance and future perspectives.

BACKGROUND: The liver is a well-known player in the metabolism and removal of drugs. Drug metabolizing enzymes in the liver detoxify drugs and xenobiotics, ultimately leading to the acquisition of homeostasis. However, liver toxicity and cell damage are not only related to the nature and dosage of a particular drug but are also influenced by other factors such as aging, immune status, environmental contaminants, microbial metabolites, gender, obesity, and expression of individual genes Furthermore, factors such as drugs, alcohol, and environmental contaminants could induce oxidative stress, thereby impairing the regenerative potential of the liver and causing several diseases. Persons suffering from other ailments and those with comorbidities are found to be more prone to drug-induced toxicities. Moreover, drug composition and drug-drug interactions could further aggravate the risk of drug-induced hepatotoxicity. A plethora of mechanisms are responsible for initiating liver cell damage and further aggravating liver cell injury, followed by impairment of homeostasis, ultimately leading to the generation of reactive oxygen species, immune-suppression, and oxidative stress. OBJECTIVE: To summarize the potential of phytochemicals and natural bioactive compounds to treat hepatotoxicity and other liver diseases. STUDY DESIGN: A deductive qualitative content analysis approach was employed to assess the overall outcomes of the research and review articles pertaining to hepatoprotection induced by natural drugs, along with analysis of the interventions. METHODS: An extensive literature search of bibliographic databases, including Web of Science, PUBMED, SCOPUS, GOOGLE SCHOLAR, etc., was carried out to understand the role of hepatoprotective effects of natural drugs. RESULTS: Bioactive natural products, including curcumin, resveratrol, etc., have been seen as neutralizing agents against the side effects induced by the drugs. Moreover, these natural products are dietary and are readily available; thus, could be supplemented along with drugs to reduce toxicity to cells. Probiotics, prebiotics, and synbiotics have shown promise of improving overall liver functioning, and these should be evaluated more extensively for their hepatoprotective potential. Therefore, selecting an appropriate natural product or a bioactive compound that is free of toxicity and offers a reliable solution for drug-induced liver toxicity is quintessential. CONCLUSIONS: The current review highlights the role of natural bioactive products in neutralizing drug-induced hepatotoxicity. Efforts have been made to delineate the possible underlying mechanism associated with the neutralization process.

ChatGPT and artificial hallucinations in stem cell research: assessing the accuracy of generated references - a preliminary study.

Stem cell research has the transformative potential to revolutionize medicine. Language models like ChatGPT, which use artificial intelligence (AI) and natural language processing, generate human-like text that can aid researchers. However, it is vital to ensure the accuracy and reliability of AI-generated references. This study assesses Chat Generative Pre-Trained Transformer (ChatGPT)'s utility in stem cell research and evaluates the accuracy of its references. Of the 86 references analyzed, 15.12% were fabricated and 9.30% were erroneous. These errors were due to limitations such as no real-time internet access and reliance on preexisting data. Artificial hallucinations were also observed, where the text seems plausible but deviates from fact. Monitoring, diverse training, and expanding knowledge cut-off can help to reduce fabricated references and hallucinations. Researchers must verify references and consider the limitations of AI models. Further research is needed to enhance the accuracy of such language models. Despite these challenges, ChatGPT has the potential to be a valuable tool for stem cell research. It can help researchers to stay up-to-date on the latest developments in the field and to find relevant information.

Novel pathologic findings and viral antigen distribution in cattle and buffalo calves naturally infected with Foot-and-Mouth disease virus.

The Foot-and-Mouth disease is highly contagious acute viral disease of livestock inflicting huge economic loss to the farmers. The limited knowledge regarding the pathological lesions vis-a-vis distribution of the FMDV in lesser explored endocrine glands and important vital organs other than the target organs of infected calves prompted us to take the present investigation to have detailed insight into the pathogenesis. The systematic necropsy of 37 dead calves (cattle-28 and buffalo-9) was conducted, and thin representative tissue pieces from the affected organs were collected in 10% neutral buffered formalin (NBF) for pathological and immunohistochemical investigations. The genomic detection and its serotyping were done by RT-PCR and multiplex-PCR, respectively. Necropsy examination in all cases showed myocardial lesions resembling 'tigroid heart appearance'. Other organ specific lesions include vesiculo-ulcerative stomatitis, edema of the lungs, petechial hemorrhages, edema of the endocrines, and gastroenteritis. Histopathological examination showed varying sizes of vesicles and ulcerations in stratified squamous epithelium of the tongue, acute necrotizing myocarditis, lymphoid depletion in lymphoid tissues, hepatitis, pancreatitis, thymic hyperplasia, thyroiditis, adrenitis, and enteritis. Positive immunolabeling for viral antigens was observed in endocrine glands, lymphoid organs, lungs, liver, kidneys, and intestine, in addition to other typical locations. The thyroid, adrenal glands, and pancreas, in addition to the tongue and heart, are the tissue of choice for sampling in the field during epidemics. Further, the viral genome and serotype A was confirmed in the affected tissues. This study provides insights into novel tissue tropism and pathogenesis in young calves naturally infected with FMDV.