The multifaceted functions of long non-coding RNA HOTAIR in neuropathologies and its potential as a prognostic marker and therapeutic biotarget.

Long non-coding RNAs (lncRNAs) are progressively being perceived as prominent molecular agents controlling multiple aspects of neuronal (patho)physiology. Amongst these is the HOX transcript antisense intergenic RNA, often abbreviated as HOTAIR. HOTAIR epigenetically regulates its target genes via its interaction with two different chromatin-modifying agents; histone methyltransferase polycomb-repressive complex 2 and histone demethylase lysine-specific demethylase 1. Parenthetically, HOTAIR elicits trans-acting sponging function against multiple micro-RNA species. Oncological research studies have confirmed the pathogenic functions of HOTAIR in multiple cancer types, such as gliomas and proposed it as a pro-oncological lncRNA. In fact, its expression has been suggested to be a predictor of the severity/grade of gliomas, and as a prognostic biomarker. Moreover, a propound influence of HOTAIR in other aspects of brain heath and disease states is just beginning to be unravelled. The objective of this review is to recapitulate all the relevant data pertaining to the regulatory roles of HOTAIR in neuronal (patho)physiology. To this end, we discuss the pathogenic mechanisms of HOTAIR in multiple neuronal diseases, such as neurodegeneration, traumatic brain injury and neuropsychiatric disorders. Finally, we also summarize the results from the studies incriminating HOTAIR in the pathogeneses of gliomas and other brain cancers. Implications of HOTAIR serving as a suitable therapeutic target in neuropathologies are also discussed.

Multirole of the internet of medical things (IoMT) in biomedical systems for managing smart healthcare systems: An overview of current and future innovative trends.

Internet of Medical Things (IoMT) is an emerging subset of Internet of Things (IoT), often called as IoT in healthcare, refers to medical devices and applications with internet connectivity, is exponentially gaining researchers' attention due to its wide-ranging applicability in biomedical systems for Smart Healthcare systems. IoMT facilitates remote health biomedical system and plays a crucial role within the healthcare industry to enhance precision, reliability, consistency and productivity of electronic devices used for various healthcare purposes. It comprises a conceptualized architecture for providing information retrieval strategies to extract the data from patient records using sensors for biomedical analysis and diagnostics against manifold diseases to provide cost-effective medical solutions, quick hospital treatments, and personalized healthcare. This article provides a comprehensive overview of IoMT with special emphasis on its current and future trends used in biomedical systems, such as deep learning, machine learning, blockchains, artificial intelligence, radio frequency identification, and industry 5.0.

Binding selectivity analysis of new delhi metallo-beta-lactamase-1 inhibitors using molecular dynamics simulations: Exploring possibilities for decoding antimicrobial drug resistance.

BACKGROUND: New Delhi metallo-beta-lactamase-1 (NDM1) confers resistance to several bacterial species against a broad range of beta-lactam antibiotics and turning them into superbugs that pose a significant threat to healthcare systems worldwide. As such, it is a potentially relevant biological target for counteracting bacterial infections. Given the lack of effective treatment options against NDM1 producing bacteria, finding a reliable inhibitor for the NDM1 enzyme is crucial. METHODS: Using molecular dynamics simulations, the binding selectivities and affinities of three ligands, viz. PNK, 3S0, and N1G were investigated against NDM1. RESULTS: The results indicate that N1G binds with more affinity to NDM1 than PNK and 3S0. The binding energy decomposition analysis revealed that residues I35, W93, H189, K211, and N220 showed significant binding energies with PNK, 3S0, and N1G, and hence are crucially involved in the binding of the ligands to NDM1. Molecular dynamics trajectory analysis further elicited that the ligands influence dynamic flexibility of NDM1 morphology, which contributes to the partial selectivities of PNK, 3S0, and N1G. CONCLUSIONS: This in silico study offers a vital information for developing potential NDM1 inhibitors with high selectivity. Nevertheless, in vitro and in vivo experimental validation is mandated to extend the possible applications of these ligands as NDM1 inhibitors that succor in combating antimicrobial resistance.

Garcinol in gastrointestinal cancer prevention: recent advances and future prospects.

Gastrointestinal cancers continue to pose a significant global health challenge, with millions of new cases diagnosed each year. Despite advancements in treatment, the prognosis for many patients remains poor. This article explores the potential of garcinol, a polyisoprenylated benzophenone found in various Garcinia species, as a therapeutic agent against gastrointestinal malignancies. The objective is to review recent research on garcinol's anticancer properties, its mechanisms of action, and safety aspects. Garcinol exhibits anticancer effects in esophageal, gastric, colorectal, pancreatic, and liver cancers by inhibiting metastasis, inducing apoptosis, and targeting key molecular pathways in cancer progression. Nanotechnology is explored as a means to enhance garcinol delivery and efficacy. Safety assessments suggest a promising toxicity profile. Garcinol shows significant potential as a natural therapeutic agent for gastrointestinal cancers, and future research is needed on optimizing its delivery, exploring synergistic combinations, and conducting clinical trials to validate its efficacy and safety for clinical applications.

Emerging challenges in antimicrobial resistance: implications for pathogenic microorganisms, novel antibiotics, and their impact on sustainability.

Overuse of antibiotics is accelerating the antimicrobial resistance among pathogenic microbes which is a growing public health challenge at the global level. Higher resistance causes severe infections, high complications, longer stays at hospitals and even increased mortality rates. Antimicrobial resistance (AMR) has a significant impact on national economies and their health systems, as it affects the productivity of patients or caregivers due to prolonged hospital stays with high economic costs. The main factor of AMR includes improper and excessive use of antimicrobials; lack of access to clean water, sanitation, and hygiene for humans and animals; poor infection prevention and control measures in hospitals; poor access to medicines and vaccines; lack of awareness and knowledge; and irregularities with legislation. AMR represents a global public health problem, for which epidemiological surveillance systems have been established, aiming to promote collaborations directed at the well-being of human and animal health and the balance of the ecosystem. MDR bacteria such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp., and Klebsiella pneumonia can even cause death. These microorganisms use a variety of antibiotic resistance mechanisms, such as the development of drug-deactivating targets, alterations in antibiotic targets, or a decrease in intracellular antibiotic concentration, to render themselves resistant to numerous antibiotics. In context, the United Nations issued the Sustainable Development Goals (SDGs) in 2015 to serve as a worldwide blueprint for a better, more equal, and more sustainable existence on our planet. The SDGs place antimicrobial resistance (AMR) in the context of global public health and socioeconomic issues; also, the continued growth of AMR may hinder the achievement of numerous SDGs. In this review, we discuss the role of environmental pollution in the rise of AMR, different mechanisms underlying the antibiotic resistance, the threats posed by pathogenic microbes, novel antibiotics, strategies such as One Health to combat AMR, and the impact of resistance on sustainability and sustainable development goals.

The Role of Phytonutrient Kaempferol in the Prevention of Gastrointestinal Cancers: Recent Trends and Future Perspectives.

In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol's efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment.

Luteolin: A promising modulator of apoptosis and survival signaling in liver cancer.

Due to the increasing incidence of cancer and the difficulties in determining the safety profile of existing therapeutic approaches, cancer research has recently become heavily involved in the search for new therapeutic approaches. The therapeutic significance of natural substances, especially flavonoids, against the onset and progression of cancer has been emphasized in traditional food-based medicine. Interestingly, the flavone luteolin possesses biological effects that have been linked to its anti-inflammatory, antioxidant, and anticancer effects. Luteolin interacts with several downstream chemicals and signaling pathways, including those involved in apoptosis, autophagy, cell cycle progression, and angiogenesis, to exert its anticancer effects on various cancerous cells. A complete understanding of both intrinsic and extrinsic apoptotic pathways, autophagy, and, most critically, the nanodelivery of luteolin in liver cancer is provided in the current review.

In silico identification of microRNAs targeting the PPARα/γ: promising therapeutics for SARS-CoV­2 infection.

The SARS-CoV-2 lifecycle is dependent on the host metabolism machinery. It upregulates the PPARα and PPARγ genes in lipid metabolism, which supports the essential viral replication complex including lipid rafts and palmitoylation of viral protein. The use of PPAR ligands in SARS-CoV-2 infection may have positive effects by preventing cytokine storm and the ensuing inflammatory cascade. The inhibition of PPARα and PPARγ genes may alter the metabolism and may disrupt the lifecycle of SARS-CoV-2 and COVID-19 progression. In the present work, we have identified possible miRNAs targeting PPARα and PPARγ in search of modulators of PPARα and PPARγ genes expression. The identified miRNAs could possibly be viewed as new therapeutic targets against COVID-19 infection.

Critical appraisal and systematic review of genes linked with cocaine addiction, depression and anxiety.

Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction, depression and anxiety (ADA). In this context, the stress-tolerance levels vary amongst individuals and genetic factors play prominent roles. Vulnerable individuals may often be drawn towards drug-addiction to combat stress. This systematic review critically appraises the relationship of various genetic factors linked with the incidences of ADA development. For coherence, we focused solely on cocaine as a substance of abuse in this study. Online scholarly databases were used to screen pertinent literature using apt keywords; and the final retrieval included 42 primary-research articles. The major conclusion drawn from this systematic analysis states that there are 51 genes linked with the development of ADA; and 3 (BDNF, PERIOD2 and SLC6A4) of them are common to all the three aspects of ADA. Further, inter-connectivity analyses of the 51 genes further endorsed the central presence of BDNF and SLC6A4 genes in the development of ADA disorders. The conclusions derived from this systematic study pave the way for future studies for the identification of diagnostic biomarkers and drug targets; and for the development of novel and effective therapeutic regimens against ADA.

In silico evaluation of the inhibitory potential of nucleocapsid inhibitors of SARS-CoV-2: a binding and energetic perspective.

The COVID-19 outbreak brought on by the SARS-CoV-2 virus continued to infect a sizable population worldwide. The SARS-CoV-2 nucleocapsid (N) protein is the most conserved RNA-binding structural protein and is a desirable target because of its involvement in viral transcription and replication. Based on this aspect, this study focused to repurpose antiviral compounds approved or in development for treating COVID-19. The inhibitors chosen are either FDA-approved or are currently being studied in clinical trials against COVID-19. Initially, they were designed to target stress granules and other RNA biology. We have utilized structure-based molecular docking and all-atom molecular dynamics (MD) simulation approach to investigate in detail the binding energy and binding modes of the different anti-N inhibitors to N protein. The result showed that five drugs including Silmitasterib, Ninetanidinb, Ternatin, Luteolin, Fedratinib, PJ34, and Zotatafin were found interacting with RNA binding sites as well as to predicted protein interface with higher binding energy. Overall, drug binding increases the stability of the complex with maximum stability found in the order, Silmitasertib > PJ34 > Zotatatafin. In addition, the frustration changes due to drug binding brings a decrease in local frustration and this decrease is mainly observed in α-helix, ß3, ß5, and ß6 strands and are important for drug binding. Our in-silico data suggest that an effective interaction occurs for some of the tested drugs and prompt their further validation to reduce the rapid outspreading of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Comprehensive deep mutational scanning reveals the pH induced stability and binding differences between SARS-CoV-2 spike RBD and human ACE2.

The SARS-CoV-2 spike (S) glycoprotein with its mobile receptor-binding domain (RBD), binds to the human ACE2 receptor and thus facilitates virus entry through low-pH-endosomal pathways. The high degree of SARS-CoV-2 mutability has raised concern among scientists and medical professionals because it created doubt about the effectiveness of drugs and vaccinations designed specifically for COVID-19. In this study, we used computational saturation mutagenesis approach, including structure-based free energy calculations to analyse the effects of the missense mutations on the SARS-CoV-2 S-RBD stability and the S-RBD binding affinity with ACE2 at three different pH (pH 4.5, pH 6.5, and pH 7.4). A total of 3705 mutations in the S-RBD protein were analyzed, and we discovered that most of these mutations destabilize the RBD protein. Specifically, residues G404, G431, G447, A475, and G526 were important for RBD protein stability. In addition, RBD residues Y449, Y489, Y495, Q498, and N487 were critical for the RBD-ACE2 interaction. Next, we found that the distribution of the mean stability changes and mean binding energy changes of RBD due to mutations at both serological and endosomal pH correlated well, indicating the similar effects of mutations. Overall, this computational analysis is useful for understanding the effects of missense mutations in SARS-CoV-2 pathogenesis at different pH.Communicated by Ramaswamy H. Sarma.

Etiology and incidence of postpartum depression among birthing women in the scenario of pandemics, geopolitical conflicts and natural disasters: a systematic review.

Postpartum depression (PPD) is classified under postpartum psychiatric disorders and initiates soon after birthing, eliciting neuropsychological and behavioral deficits in mothers and offspring. Globally, PPD is estimated to be associated with 130-190 per 1000 birthing. The severity and incidences of PPD have aggravated in the recent years due to the several unfavorable environmental and geopolitical circumstances. The purpose of this systematic review hence is to explore the contributions of recent circumstances on the pathogenesis and incidence of PPD. The search, selection and retrieval of the articles published during the last three years were systematically performed. The results from the primary studies indicate that unfavorable contemporary socio-geopolitical and environmental circumstances (e.g. Covid-19 pandemic, political conflicts/wars, and natural calamities; such as floods and earthquakes) detrimentally affect PPD etiology. A combination of socio-economic and psychological factors, including perceived lack of support and anxiousness about the future may contribute to drastic aggravation of PPD incidences. Finally, we outline some of the potential treatment regimens (e.g. inter-personal psycho- and art-based therapies) that may prove to be effective in amelioration of PPD-linked symptoms in birthing women, either alone or in complementation with traditional pharmacological interventions. We propose these psychological and art-based intervention strategies may beneficially counteract the negative influences of the unfortunate recent events across multiple cultures, societies and geographical regions.

SARS-CoV-2 origins: zoonotic Rhinolophus vs contemporary models.

The question of the origin of coronavirus spread like wildfire ever since it wreaked havoc among humankind, and ever since the scientific community has worked tirelessly to trace the history of the virus. In this review, we have tried to compile relevant literature pertaining to the different theories of origin of SARS-CoV-2, hopefully without any bias, and we strongly support the zoonotic origin of the infamous SARS-CoV-2 in bats and its transfer to human beings through the most probable evolutionary hosts, pangolins and minks. We also support the contemporary 'Circulation Model' that simply mirrors the concept of evolution to explain the origin of the virus which, the authors believe, is the most rational school of thought. The most recent variant of SARS-CoV-2, Omicron, has been taken as an example to clarify the concept. We recommend the community to refer to this model for further understanding and delving deep into this mystery of the origin of SARS-CoV-2.

Bioplatforms in liquid biopsy: advances in the techniques for isolation, characterization and clinical applications.

Tissue biopsy analysis has conventionally been the gold standard for cancer prognosis, diagnosis and prediction of responses/resistances to treatments. The existing biopsy procedures used in clinical practice are, however, invasive, painful and often associated with pitfalls like poor recovery of tumor cells and infeasibility for repetition in single patients. To circumvent these limitations, alternative non-invasive, rapid and economical, yet sturdy, consistent and dependable, biopsy techniques are required. Liquid biopsy is an emerging technology that fulfills these criteria and potentially much more in terms of subject-specific real-time monitoring of cancer progression, determination of tumor heterogeneity and treatment responses, and specific identification of the type and stages of cancers. The present review first briefly revisits the state-of-the-art technique of liquid biopsy and then proceeds to address in detail, the advances in the potential clinical applications of four major biological agencies present in liquid biopsy samples (circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes and tumor-educated platelets (TEPs)). Finally, the authors conclude with the limitations that need to be addressed in order for liquid biopsy to effectively replace the conventional invasive biopsy methods in the clinical settings.