Self-reported side effects of COVID-19 vaccines among health professions students in India.

Studies focusing on the safety and common side effects of vaccines play a crucial role in enhancing public acceptance of vaccination. Research is scarce regarding the usage of COVID-19 vaccines and the side effects experienced by health professions students in India and other countries. This study aimed to document self-reported side effects associated with COVID-19 vaccination among medical and dental students of six medical and dental colleges and teaching hospitals in four states (Tamil Nadu, Madhya Pradesh, Gujarat, and West Bengal) of India. A cross-sectional survey using purposive sampling of medical and dental students was conducted from 26 April to 26 May 2021. Data was collected using a Google Forms questionnaire capturing information regarding receiving COVID-19 vaccines, side effects and symptoms, onset and duration of symptoms, use of treatment to alleviate symptoms, awareness of haematologic risks associated with vaccination, and side effects from previous (non-COVID-19) vaccinations. The majority (94.5%) of participants received both doses of the Covishield/AstraZeneca COVID-19 vaccine. Among participants (n = 492), 45.3% (n = 223) reported one or more side effects. The most frequently reported side effects were soreness of the injected arm (80.3%), tiredness (78.5%), fever (71.3%), headache (64.1%), and hypersomnia (58.7%). The two most common severe symptoms were fever (14.8%) and headache (13%). Most side effects appeared on the day of vaccination: soreness of the injection site (57%), fever (43.1%), and tiredness (42.6%). Most reported symptoms persisted for one to three days-soreness of the injection site (53%), fever (47.1%), and headache (42.6%). Logistic regression showed that women were almost 85% less likely to report side effects. The study's findings corroborate the safety of the Covishield/AstraZeneca vaccine's first dose, evidenced by the relatively minor and transient nature of the side effects. However, the study underscores the necessity for ongoing research to assess the long-term impacts of COVID-19 vaccines, especially in the context of booster doses, thereby contributing to the global understanding of vaccine safety and efficacy.

Knowledge, Attitudes, and Practices of Hand Hygiene, Mask Use, and Social Distancing among Public Hospital and Polyclinic Nurses in Barbados during the Coronavirus 2019 Pandemic.

BACKGROUND: Nurses are essential members of the healthcare workforce and were among the first-line carers for patients in community and hospital settings during the COVID-19 pandemic. As a result, they were at a heightened risk of infection, resulting in several reported deaths among nursing staff. Several preventive measures were adopted to contain the spread of the COVID-19 virus. This study aims to explore the knowledge, attitudes, and practices (KAP) of nurses regarding hand hygiene, mask wearing, and social distancing measures in healthcare settings in Barbados during the COVID-19 pandemic. METHOD: An online survey of nurses working in public hospitals and polyclinics (public primary care clinics) in Barbados from March 2021 to December 2021 was conducted. A nonsystematic convenience sampling method was employed to recruit nurses who were readily available and willing to participate. A questionnaire captured the sociodemographic information and knowledge and practices related to hand hygiene, the use of face masks, and social distancing. Each correct response received one mark. Overall knowledge scores were categorized as poor (<60%), average (60-80%), or good (>80-100%). RESULTS: Of the 192 participants, the majority were female (82.8%) and had >5 years of experience (82%). The findings revealed that 45.8% had poor knowledge of hand hygiene, and that the knowledge of 43.8% of respondents was average. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 2.1 times increased odds (95% confidence interval 1.0, 4.2) of having good knowledge compared to other nursing categories. Regarding mask wearing, 53.6% of nurses had average knowledge, and 27.1% had good knowledge. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 3.3 times increased odds (95% confidence interval 1.5, 7.4) of having good knowledge compared to nursing assistants. A total of 68.6% of respondents followed the correct steps of handwashing every time, and 98.3% wore a mask in public places. More than half of the nurses (51.2%) kept a safe distance from others to avoid spreading SARS-CoV-2; one-third were in a crowded place(s) in the past three months, and 55.8% usually followed guidelines for social isolation as recommended by the WHO. CONCLUSIONS: The study identified knowledge deficiencies related to hand hygiene and wearing masks among nurses. It is imperative to provide additional training on infection control measures.

Evaluation of Short-Term Side Effects Following the First Dose of COVID-19 Vaccines Among Physicians and Dentists: A Cross-Sectional Study from India.

Background: Efficacy and safety are fundamental for the development of successful COVID-19 vaccines. Vaccine-associated side effects influence vaccine hesitancy. This study investigated the prevalence, severity, and onset of side effects following the first dose of COVID-19 vaccines among physicians and dentists working in various healthcare settings across India. Methods: A cross-sectional survey collected self-report data from April to June 2021 on side effects following the first dose of the vaccine. An online validated questionnaire using the Google Docs® platform was circulated via email and social media platforms. Results: More than 40% of participants experienced at least one side effect after the first dose of vaccination; the most common were mild and resolved within three days after vaccination. More than 91% of respondents received the Covishield (AstraZeneca) vaccine; the most prevalent adverse effects were soreness of the injected arm (78.9%), tiredness (71.1%), and fever (54.9%). Logistic regression showed that women were almost 60% less likely to report side effects. Conclusion: Findings supported the safety of the first dose of the COVID-19 vaccine based on relatively few self-limiting side effects, mainly soreness of the injected arm and tiredness. Further research is needed to determine the long-term safety of COVID-19 vaccines, especially after booster doses.

Quetiapine Shortens the Lifespan of Caenorhabditis elegans through DOP-2, DAF-2 and RSKS-1.

Recent studies implicate a key role of dopamine signaling in lifespan regulation. Our previous study found that quetiapine, an atypical antipsychotic drug that has antagonistic activity on dopamine D2-like receptors (D2Rs), shortened the lifespan of Caenorhabditis elegans (C. elegans). However, the detailed mechanism of this effect was not clear. In the present study, we evaluate the effect of quetiapine on aging and explore its underlying molecular mechanism. The results show that quetiapine shortened healthspan in C. elegans. The lifespan-shortening effect is dependent on DOP-2, a D2R expressed in worms. Quetiapine shortens lifespan through the C. elegans insulin and IGF-1 receptor DAF-2, but not the downstream Akt pathway. Quetiapine-induced lifespan reduction is dependent on RSKS-1, a key protein kinase that functions in mTOR signaling. In addition, the quetiapine effect is also related to mitochondrial function. These findings further support the key role of dopamine signaling in lifespan regulation and promote our insight into the mechanism of action of antipsychotic drugs.

Dopamine D1- and D2-like receptors oppositely regulate lifespan via a dietary restriction mechanism in Caenorhabditis elegans.

BACKGROUND: Despite recent progress in understanding the molecular mechanisms regulating aging and lifespan, and the pathways involved being conserved in different species, a full understanding of the aging process has not been reached. In particular, increasing evidence suggests an active role for the nervous system in lifespan regulation, with sensory neurons, as well as serotonin and GABA signaling, having been shown to regulate lifespan in Caenorhabditis elegans (C. elegans). However, the contribution of additional neural factors, and a broad understanding of the role of the nervous system in regulating aging remains to be established. Here, we examine the impact of the dopamine system in regulating aging in C. elegans. RESULTS: We report that mutations of DOP-4, a dopamine D1-like receptor (D1R), and DOP-2, a dopamine D2-like receptor (D2R) oppositely affected lifespan, fast body movement span, reproductive lifespan, and developmental rate in C. elegans. Activation of D2R using aripiprazole, an antipsychotic drug, robustly extended both lifespan and healthspan. Conversely, inhibition of D2R using quetiapine shortened worm lifespan, further supporting the role of dopamine receptors in lifespan regulation. Mechanistically, D2R signaling regulates lifespan through a dietary restriction mechanism mediated by the AAK-2-DAF-16 pathway. The DAG-PKC/PKD pathway links signaling between dopamine receptors and the downstream AAK-2-DAF-16 pathway to transmit longevity signals. CONCLUSIONS: These data demonstrated a novel role of dopamine receptors in lifespan and dietary restriction regulation. The clinically approved antipsychotic aripiprazole holds potential as a novel anti-aging drug.

Inhibitor GSK690693 extends Drosophila lifespan via reduce AKT signaling pathway.

Aging is a process involving physiological changes that lead to the decline of biological functions of various tissues and organs of the body. Therefore, it is crucial to find anti-aging drugs that can intervene with the changes induced because of aging and slow down the degeneration of the biological functions. Among many signaling pathways linked with aging and aging-related diseases, PI3K-AKT signaling pathway has attracted major attention in aging biology. In this research paper, we have demonstrated that AKT inhibitor GSK690693 can extend lifespan in Drosophila irrespective of start of the treatment from the beginning of life or the mid-life. Effect of GSK690693 for lifespan extension has been primarily related to the improvements in oxidative resistance, intestinal integrity and increased autophagy, but not in physical activity or starvation resistance. Furthermore, GSK690693 treatment reduced the activation of AKT and ERK, consequently activating FOXO, GSK-3ß and apoptosis to modulate longevity of flies. Remarkably, GSK690693 did not induce hyperglycemia after treatment. The results indicate that GSK690693 may become an effective compound for anti-aging intervention.

Impact of COVID-19 pandemic on radiology education, training, and practice: A narrative review.

Radiology education and training is of paramount clinical importance given the prominence of medical imaging utilization in effective clinical practice. The incorporation of basic radiology in the medical curriculum has continued to evolve, focusing on teaching image interpretation skills, the appropriate ordering of radiological investigations, judicious use of ionizing radiation, and providing exposure to interventional radiology. Advancements in radiology have been driven by the digital revolution, which has, in turn, had a positive impact on radiology education and training. Upon the advent of the corona virus disease 2019 (COVID-19) pandemic, many training institutions and hospitals adhered to directives which advised rescheduling of non-urgent outpatient appointments. This inevitably impacted the workflow of the radiology department, which resulted in the reduction of clinical in-person case reviews and consultations, as well as in-person teaching sessions. Several medical schools and research centers completely suspended face-to-face academic activity. This led to challenges for medical teachers to complete the radiology syllabus while ensuring that teaching activities continued safely and effectively. As a result, online teaching platforms have virtually replaced didactic face-to-face lectures. Radiology educators also sought other strategies to incorporate interactive teaching sessions while adopting the e-learning approach, as they were cognizant of the limitations that this may have on students' clinical expertise. Migration to online methods to review live cases, journal clubs, simulation-based training, clinical interaction, and radiology examination protocolling are a few examples of successfully addressing the limitations in reduced clinical exposure. In this review paper, we discuss (1) The impact of the COVID-19 pandemic on radiology education, training, and practice; (2) Challenges and strategies involved in delivering online radiology education for undergraduates and postgraduates during the COVID-19 pandemic; and (3) Difference between the implementation of radiology education during the COVID-19 pandemic and pre-COVID-19 era.

Disparity in biomedical publication trends in the CARICOM countries: Is there a need for a more vibrant research culture in the region?

BACKGROUND: Biomedical research and publications provide evidence-based information about the extent and burden of health-related problems of a country and help to formulate strategic and operational plans to tackle the problems. PURPOSE: To determine the biomedical publication rates of CARICOM full member countries. METHODS: Biomedical publications of full member CARICOM countries were retrieved using PubMed (1990-2015) and SCImago Journal & Country Rank (1996-2015) databases. CARICOM countries having >50 publications in the PubMed (1990-2015) database were subject to further analysis, whereby publications of each country were adjusted by total population (million population), gross domestic product (billion-dollar), and Internet usage rate (hundred thousand population). RESULTS: Total publications by all countries were 7281 and 8378 in PubMed and SCImago Journal & Country Rank, respectively. Jamaica produced highest number of publications (PubMed: 3928 (53.9%); SCImago Journal & Country Rank: 2850 (34.0%)). In both databases, Grenada had the highest research publications when adjusted with per million population (4721 and 10,633), per billion gross domestic product (803 and 1651), and per hundred thousand Internet users (1487 and 3387). Trend analysis revealed Jamaica produced the highest number of additional PubMed listed publications each year, averaging 4.8/year, followed by Trinidad and Tobago (4.4). According to SCImago Journal & Country Rank, Jamaica also had the highest number of citations (42,311) and h-index (76), followed by Trinidad and Tobago (29,152 and 71). Barbados had the highest number of citations per document (24.9), followed by Haiti (18.4). The publication rates determined by PubMed and SCImago Journal & Country Rank databases were significantly correlated (p < 0.001). Most publications (68% SCImago Journal & Country Rank and 85% PubMed) can be attributed to authors affiliated with Barbados, Jamaica, and Trinidad. CONCLUSION: Publication and citation rates varied markedly between CARICOM countries and were in general low. Most publications could be attributed to researchers affiliated with The University of the West Indies. More universities valuing biomedical research are needed in the region, and more resources needed to improve publication rates.

Comparative proteomics analysis of dietary restriction in Drosophila.

To explore the underlying mechanism of dietary restriction (DR) induced lifespan extension in fruit flies at protein level, we performed proteome sequencing in Drosophila at day 7 (young) and day 42 (old) under DR and ad libitum (AL) conditions. A total of 18629 unique peptides were identified in Uniprot, corresponding to 3,662 proteins. Among them, 383 and 409 differentially expressed proteins (DEPs) were identified from comparison between DR vs AL at day 7 and 42, respectively. Bioinformatics analysis revealed that membrane-related processes, post-transcriptional processes, spliceosome and reproduction related processes, were highlighted significantly. In addition, expression of proteins involved in pathways such as spliceosomes, oxidative phosphorylation, lysosomes, ubiquitination, and riboflavin metabolism was relatively higher during DR. A relatively large number of DEPs were found to participate in longevity and age-related disease pathways. We identified 20 proteins that were consistently regulated during DR and some of which are known to be involved in ageing, such as mTORC1, antioxidant, DNA damage repair and autophagy. In the integration analysis, we found 15 genes that were stably regulated by DR at both transcriptional as well as translational levels. Our results provided a useful dataset for further investigations on the mechanism of DR and aging.

Challenges and Opportunities of Preclinical Medical Education: COVID-19 Crisis and Beyond.

COVID-19 pandemic has disrupted face-to-face teaching in medical schools globally. The use of remote learning as an emergency measure has affected students, faculty, support staff, and administrators. The aim of this narrative review paper is to examine the challenges and opportunities faced by medical schools in implementing remote learning for basic science teaching in response to the COVID-19 crisis. We searched relevant literature in PubMed, Scopus, and Google Scholar using specific keywords, e.g., "COVID-19 pandemic," "preclinical medical education," "online learning," "remote learning," "challenges," and "opportunities." The pandemic has posed several challenges to premedical education (e.g., suspension of face-to-face teaching, lack of cadaveric dissections, and practical/laboratory sessions) but has provided many opportunities as well, such as the incorporation of online learning in the curriculum and upskilling and reskilling in new technologies. To date, many medical schools have successfully transitioned their educational environment to emergency remote teaching and assessments. During COVID-19 crisis, the preclinical phase of medical curricula has successfully introduced the novel culture of "online home learning" using technology-oriented innovations, which may extend to post-COVID era to maintain teaching and learning in medical education. However, the lack of hands-on training in the preclinical years may have serious implications on the training of the current cohort of students, and they may struggle later in the clinical years. The use of emergent technology (e.g., artificial intelligence for adaptive learning, virtual simulation, and telehealth) for education is most likely to be indispensable components of the transformative change and post-COVID medical education.

Keloids: Current and emerging therapies.

Keloids are pathological scars that grow over time and extend beyond the initial site of injury after impaired wound healing. These scars frequently recur and rarely regress. They are aesthetically disfiguring, can cause pain, itching, discomfort as well as psychological stress, often affecting quality of life. Many treatment modalities, including surgical and non-surgical, have been explored and have been reported to be beneficial; however, none have been absolutely satisfactory or optimal for the treatment of all keloid subtypes to date. This poses a major challenge to clinicians. Often, a combinational therapeutic approach appears to offer the best results with higher patient satisfaction compared to monotherapy. The aetiopathogenesis of keloids is not fully elucidated; however, with recent advances in molecular biology and genetics, insight is being gained on the complex process of scar formation and hence new therapeutic and management options for keloids. In this paper, we explore the literature and summarise the general concepts surrounding keloid development and review both current (corticosteroids, surgical excision, silicone-based products, pressure therapy, radiotherapy, cryotherapy, laser therapy, imiquimod and 5-fluorouracil) and emerging (stem cell therapy, mitomycin C, verapamil, interferons, bleomycin, botulinum toxin type A and angiotensin-converting enzyme inhibitors) treatments. Increased knowledge and understanding in this area may potentially lead to the discovery and development of novel therapeutic options that are more efficacious for all keloid types. LAY SUMMARY: Keloids are problematic scars that are difficult to treat and manage. The aetiopathogenesis of keloids is not clear; however, recent advances in molecular biology and genetics are beginning to shed light on the underlying mechanisms implicated in keloid scar formation which will hopefully lead to the development of treatment options for all keloid types. This review summarises current and emerging therapies.

Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway.

The most common form of dementia is Alzheimer's disease which is characterized by memory loss and cognitive disorders. The pathogenesis of Alzheimer's disease is not known at present but toxicity of amyloid-beta is one of the central hypotheses. Amyloid-beta can stimulate the production of reactive oxygen species (ROS), cause oxidative stress, damage mitochondrial, cause inflammatory reactions and activate apoptosis related factors which lead to the neuronal death. In this study, we found that artemisinin, a first line antimalarial drug used in clinic for decades, improved the cognitive functions in Alzheimer's disease animal model 3xTg mice. Further study showed that artemisinin reduced the deposition of amyloid-beta and tau protein, reduced the release of inflammation factors and apoptosis factors, and thereby reduced the neuronal cell death. Western blot assay showed that artemisinin stimulated the activation of ERK/CREB signaling pathway. Consistent with these results, artemisinin concentration-dependently promoted the survival of SH-SY5Y cell against toxicity of amyloid-beta protein 1-42 induced ROS accumulation, caspase activation and apoptosis. Artemisinin also stimulated the phosphorylation of ERK1/2 and CREB in SH-SY5Y cells in time and concentration-dependent manner. Inhibition of ERK/CREB pathway attenuated the protective effect of artemisinin. These data put together suggested that artemisinin has the potential to protect neuronal cells in vitro as well as in vivo animal model 3xTg mice via, at least in part, the activation of the ERK/CREB pathway. Our findings also strongly support the potential of artemisinin as a new multi-target drug that can be used for preventing and treating the Alzheimer's disease.

Pharmacological Treatment of Alzheimer's Disease: Insights from Drosophila melanogaster.

Aging is an ineluctable law of life. During the process of aging, the occurrence of neurodegenerative disorders is prevalent in the elderly population and the predominant type of dementia is Alzheimer's disease (AD). The clinical symptoms of AD include progressive memory loss and impairment of cognitive functions that interfere with daily life activities. The predominant neuropathological features in AD are extracellular ß-amyloid (Aß) plaque deposition and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated Tau. Because of its complex pathobiology, some tangible treatment can only ameliorate the symptoms, but not prevent the disease altogether. Numerous drugs during pre-clinical or clinical studies have shown no positive effect on the disease outcome. Therefore, understanding the basic pathophysiological mechanism of AD is imperative for the rational design of drugs that can be used to prevent this disease. Drosophila melanogaster has emerged as a highly efficient model system to explore the pathogenesis and treatment of AD. In this review we have summarized recent advancements in the pharmacological research on AD using Drosophila as a model species, discussed feasible treatment strategies and provided further reference for the mechanistic study and treatment of age-related AD.

Artemisinin Protects Human Retinal Pigmented Epithelial Cells Against Hydrogen Peroxide-induced Oxidative Damage by Enhancing the Activation of AMP-active Protein Kinase.

Dry age-related macular degeneration (AMD), a leading cause of blindness in aged population, is directly associated with oxidative stress induced damage of the retinal pigmented epithelial (RPE) cells. In the current study, we investigated the role of AMPK in the protective effect of artemisinin, an FDA approved anti-malarial Chinese herbal drug, on RPE cell line D407, against H2O2 induced oxidative stress. Our results showed that artemisinin promoted the survival of D407 cells from H2O2. Artemisinin reduced intracellular ROS generation and oxidative stress, decreased LDH release and the loss of mitochondrial membrane potential in D407 cells treated with H2O2. Western blotting showed that artemisinin concentration- and time-dependently stimulated the phosphorylation of AMP-activated protein kinase (AMPK) in D407 cells while AMPK inhibitor Compound C or knock-down of AMPK by si-RNA, inhibited the survival protective effect of artemisinin. More importantly, artemisinin produced a similar protective effect in primary cultured retinal pigment cells which was also blocked by inhibitors of AMPK. Taken together, these results suggested that artemisinin promotes survival of human retinal pigment cells against H2O2-induced cell death at least in part through enhancing the activation of AMPK. Therefore, artemisinin may be a beneficial therapeutic candidate for the treatment of age-related diseases, including retinal disorders like AMD.

Role of Corticotropin Releasing Factor in the Neuroimmune Mechanisms of Depression: Examination of Current Pharmaceutical and Herbal Therapies.

Approximately 3% of the world population suffers from depression, which is one of the most common form of mental disorder. Recent findings suggest that an interaction between the nervous system and immune system might be behind the pathophysiology of various neurological and psychiatric disorders, including depression. Neuropeptides have been shown to play a major role in mediating response to stress and inducing immune activation or suppression. Corticotropin releasing factor (CRF) is a major regulator of the hypothalamic pituitary adrenal (HPA) axis response. CRF is a stress-related neuropeptide whose dysregulation has been associated with depression. In this review, we summarized the role of CRF in the neuroimmune mechanisms of depression, and the potential therapeutic effects of Chinese herbal medicines (CHM) as well as other agents. Studying the network of CRF and immune responses will help to enhance our understanding of the pathogenesis of depression. Additionally, targeting this important network may aid in developing novel treatments for this debilitating psychiatric disorder.

14-3-3 Proteins Are on the Crossroads of Cancer, Aging, and Age-Related Neurodegenerative Disease.

14-3-3 proteins are a family of conserved regulatory adaptor molecules which are expressed in all eukaryotic cells. These proteins participate in a variety of intracellular processes by recognizing specific phosphorylation motifs and interacting with hundreds of target proteins. Also, 14-3-3 proteins act as molecular chaperones, preventing the aggregation of unfolded proteins under conditions of cellular stress. Furthermore, 14-3-3 proteins have been shown to have similar expression patterns in tumors, aging, and neurodegenerative diseases. Therefore, we put forward the idea that the adaptor activity and chaperone-like activity of 14-3-3 proteins might play a substantial role in the above-mentioned conditions. Interestingly, 14-3-3 proteins are considered to be standing at the crossroads of cancer, aging, and age-related neurodegenerative diseases. There are great possibilities to improve the above-mentioned diseases and conditions through intervention in the activity of the 14-3-3 protein family.

Artemisinin Attenuated Hydrogen Peroxide (H2O2)-Induced Oxidative Injury in SH-SY5Y and Hippocampal Neurons via the Activation of AMPK Pathway.

Oxidative stress is believed to be one of the main causes of neurodegenerative diseases such as Alzheimer's disease (AD). The pathogenesis of AD is still not elucidated clearly but oxidative stress is one of the key hypotheses. Here, we found that artemisinin, an anti-malarial Chinese medicine, possesses neuroprotective effects. However, the antioxidative effects of artemisinin remain to be explored. In this study, we found that artemisinin rescued SH-SY5Y and hippocampal neuronal cells from hydrogen peroxide (H2O2)-induced cell death at clinically relevant doses in a concentration-dependent manner. Further studies showed that artemisinin significantly restored the nuclear morphology, improved the abnormal changes in intracellular reactive oxygen species (ROS), reduced the mitochondrial membrane potential, and caspase-3 activation, thereby attenuating apoptosis. Artemisinin also stimulated the phosphorylation of the adenosine monophosphate -activated protein kinase (AMPK) pathway in SH-SY5Y cells in a time- and concentration-dependent manner. Inhibition of the AMPK pathway attenuated the protective effect of artemisinin. These data put together suggested that artemisinin has the potential to protect neuronal cells. Similar results were obtained in primary cultured hippocampal neurons. Cumulatively, these results indicated that artemisinin protected neuronal cells from oxidative damage, at least in part through the activation of AMPK. Our findings support the role of artemisinin as a potential therapeutic agent for neurodegenerative diseases.

Population genomics identifies patterns of genetic diversity and selection in chicken.

BACKGROUND: There are hundreds of phenotypically distinguishable domestic chicken breeds or lines with highly specialized traits worldwide, which provide a unique opportunity to illustrate how selection shapes patterns of genetic variation. There are many local chicken breeds in China. RESULTS: Here, we provide a population genome landscape of genetic variations in 86 domestic chickens representing 10 phenotypically diverse breeds. Genome-wide analysis indicated that sex chromosomes have less genetic diversity and are under stronger selection than autosomes during domestication and local adaptation. We found an evidence of admixture between Tibetan chickens and other domestic population. We further identified strong signatures of selection affecting genomic regions that harbor genes underlying economic traits (typically related to feathers, skin color, growth, reproduction and aggressiveness) and local adaptation (to high altitude). By comparing the genomes of the Tibetan and lowland fowls, we identified genes associated with high-altitude adaptation in Tibetan chickens were mainly involved in energy metabolism, body size maintenance and available food sources. CONCLUSIONS: The work provides crucial insights into the distinct evolutionary scenarios occurring under artificial selection for agricultural production and under natural selection for success at high altitudes in chicken. Several genes were identified as candidates for chicken economic traits and other phenotypic traits.

Metformin protects PC12 cells and hippocampal neurons from H2 O 2 -induced oxidative damage through activation of AMPK pathway.

Metformin, a first line anti type 2 diabetes drug, has recently been shown to extend lifespan in various species, and therefore, became the first antiaging drug in clinical trial. Oxidative stress due to excess reactive oxygen species (ROS) is considered to be an important factor in aging and related disease, such as Alzheimer's disease (AD). However, the antioxidative effects of metformin and its underlying mechanisms in neuronal cells is not known. In the present study, we showed that metformin, in clinically relevant concentrations, protected neuronal PC12 cells from H2 O2 -induced cell death. Metformin significantly ameliorated cell death due to H2 O2 insult by restoring abnormal changes in nuclear morphology, intracellular ROS, lactate dehydrogenase, and mitochondrial membrane potential induced by H2 O2 . Hoechst staining assay and flow cytometry analysis revealed that metformin significantly reduced the apoptosis in PC12 cells exposed to H2 O2 . Western blot analysis further demonstrated that metformin stimulated the phosphorylation and activation of AMP-activated protein kinase (AMPK) in PC12 cells, while application of AMPK inhibitor compound C, or knockdown of the expression of AMPK by specific small interfering RNA or short hairpin RNA blocked the protective effect of metformin. Similar results were obtained in primary cultured hippocampal neurons. Taken together, these results indicated that metformin is able to protect neuronal cells from oxidative injury, at least in part, via the activation of AMPK. As metformin is comparatively cheaper with much less side effects in clinic, our findings support its potential to be a drug for prevention and treatment of aging and aging-related diseases.

Pharmacoinformatic Approach to Explore the Antidote Potential of Phytochemicals on Bungarotoxin from Indian Krait, Bungarus caeruleus.

Venomous reptiles especially serpents are well known for their adverse effects after accidental conflicts with humans. Upon biting humans these serpents transmit arrays of detrimental toxins with diverse physiological activities that may either lead to minor symptoms such as dermatitis and allergic response or highly severe symptoms such as blood coagulation, disseminated intravascular coagulation, tissue injury, and hemorrhage. Other complications like respiratory arrest and necrosis may also occur. Bungarotoxins are a group of closely related neurotoxic proteins derived from the venom of kraits (Bungarus caeruleus) one of the six most poisonous snakes in India whose bite causes respiratory paralysis and mortality without showing any local symptoms. In the current study, by employing various pharmacoinformatic approaches, we have explored the antidote properties of 849 bioactive phytochemicals from 82 medicinal plants which have already shown antidote properties against various venomous toxins. These herbal compounds were taken and pharmacoinformatic approaches such as ADMET, docking and molecular dynamics were employed. The three-dimensional modelling approach provides structural insights on the interaction between bungarotoxin and phytochemicals. In silico simulations proved to be an effective analytical tools to investigate the toxin-ligand interaction, correlating with the affinity of binding. By analyzing the results from the present study, we proposed nine bioactive phytochemical compounds which are, 2-dodecanol, 7-hydroxycadalene, indole-3-(4'-oxo)butyric acid, nerolidol-2, trans-nerolidol, eugenol, benzene propanoic acid, 2-methyl-1-undecanol, germacren-4-ol can be used as antidotes for bungarotoxin.