Advancing Equity in Health Care Among Dalits and Tribal People in India: The Progress, Current Realities, and the Way Forward.

The caste system and resulting social exclusion are important social determinants of health inequity in India. This article critically analyzes the influence of the caste system on health inequity in India, starting with a historical perspective and moving to the current status. The article argues that the caste system has deprived Dalits and tribal people in India of achieving health equity. The programs to promote health are often disease-specific and not culturally informed, leading to poor attention at the policy level to the intersecting disadvantages that make Dalits and tribal communities vulnerable, resulting in poor health. The authors suggest strengthening and promoting primary care, improving health access for Dalit and tribal populations, and the need for pivotal changes in the medical education system, shifting the emphasis from specialized care to training family physicians to be oriented toward community health needs, keeping health equity in perspective.

Commercial Enzyme-Linked Immunosorbent Assay Kit Is Useful for Detection of Recombinant and Secretory Nonstructural-1 Protein Antigen of Dengue Virus.

Background: Dengue is a mosquito-borne tropical disease, caused by the Dengue virus (DENV). It has become a severe problem and is a rising threat to public health. In this study, we have evaluated commercial Merilisa i Dengue NS1 Antigen kit (Meril LifeSciences India Pvt. Ltd.) to detect recombinant dengue virus 2 NS1 antigen (rDNS1Ag) and secreted forms of NS1 antigen (sDNS1Ag). Methods: To determine the detection limit of the kit, 100 nanogram (ng) to 0.001 ng rDNS1Ag was tested. The sensitivity and specificity of the kit was determined using recombinant NS1 antigens of all serotypes of DENV and other flaviviruses. For testing sDNS1Ag, the culture supernatant of the Vero cell lines infected with DENV-2 was tested. Further, a spiking experiment was carried out to check the sensitivity of the kit to detect rDNS1Ag in the pools of Aedes aegypti mosquitoes. Results: It was observed that the kit can detect the rDNS1Ag at 1 ng concentration. The kit was sensitive to detect NS1 antigen of DENV-1, DENV-2 and DENV-3 serotypes and specific for detection of only DNS1Ag as it did not cross-react with NS1 antigen of flaviviruses. The kit was sensitive to detect rDNS1Ag in the mosquito pools as well. In addition, the kit was able to detect the sDNS1Ag in Vero cell culture supernatant. Conclusions: Overall, we observed that the Merilisa i Dengue NS1 Ag kit is sensitive and specific for the detection of DNS1Ag both in recombinant and secretory forms.

Circular RNA as a Biomarker for Diagnosis, Prognosis and Therapeutic Target in Acute and Chronic Lymphoid Leukemia.

Circular RNAs (circRNAs) are single-stranded RNAs that have received much attention in recent years. CircRNAs lack a 5' head and a 3' poly-A tail. The structure of this type of RNAs make them resistant to digestion by exonucleases. CircRNAs are expressed in different cells and have various functions. The function of circRNAs is done by sponging miRNAs, changing gene expression, and protein production. The expression of circRNAs changes in different types of cancers, which causes changes in cell growth, proliferation, differentiation, and apoptosis. Changes in the expression of circRNAs can cause the invasion and progression of tumors. Studies have shown that changes in the expression of circRNAs can be seen in acute lymphoid leukemia (ALL) and chronic lymphoid leukemia (CLL). The conducted studies aim to identify circRNAs whose expression has changed in these leukemias and their more precise function so that these circRNAs can be identified as biomarkers, prediction of patient prognosis, and treatment targets for ALL and CLL patients. In this study, we review the studies conducted on the role and function of circRNAs in ALL and CLL patients. The results of the studies show that there is a possibility of using circRNAs as biomarkers in the identification and treatment of patients in the future.

Antioxidants for Skin Health.

Antioxidants play a pivotal role in maintaining skin health and integrity, combating the deleterious effects of oxidative stress induced by environmental aggressors such as UV ra-diation, pollution, and lifestyle factors. This paper reviews the contributions of key antioxidants, including Vitamin C, Vitamin E, Vitamin A, green tea extract, Coenzyme Q10, Resveratrol, Selenium, and Polyphenols, in skin health care. Vitamin C, known for its collagen synthesis promotion and photoprotection properties, alongside Vitamin E, a lipid-soluble antioxidant, syn-ergistically works to neutralize free radicals and repair damaged skin cells. Vitamin A, in the form of retinol, plays a critical role in skin cell regeneration and the maintenance of skin integ-rity. Green tea extract, rich in Polyphenols, offers anti-inflammatory and anticarcinogenic prop-erties, making it a potent ingredient for skin protection. Coenzyme Q10, a naturally occurring antioxidant in the body, aids in energy production for cell repair and regeneration, while Resveratrol, found in grapes and berries, provides anti-ageing benefits by enhancing skin's re-sistance to oxidative stress. Selenium, an essential mineral, contributes to the protection of skin cells from oxidative damage. The incorporation of these antioxidants in skincare products and dietary sources is discussed, highlighting the importance of a holistic approach in skincare re-gimes. The paper emphasizes the synergy between topical applications and dietary intake of antioxidants, advocating for a comprehensive strategy for promoting skin health and preventing age-related skin alterations. Method: For the review article, a variety of search engines and databases were used to identify relevant articles. Furthermore, for biomedical literature focusing on antioxidants and their ef-fects on skin health, PubMed was used. Moreover, to access a wide range of scholarly articles, including those related to dermatology and skincare, Google Scholar was used. Scopus provides comprehensive coverage of peer-reviewed literature across various scientific disciplines. Web of Science identifies high-impact articles and research on antioxidants in skincare. In addition, for accessing full-text articles on antioxidants and their applications in dermatology, Science Direct was used. The inclusion criteria for the review paper were as follows: only studies pub-lished in peer-reviewed journals were included to ensure the credibility and reliability of the information. Articles published in English were considered, to avoid language-related biases and ensure comprehension. Studies published within the last 10 years were included to provide the most current insights into antioxidant research in skincare. Articles must specifically focus on the role of antioxidants (Vitamin C, Vitamin E, Vitamin A, green tea extract, Coenzyme Q10, Resveratrol, Selenium, Polyphenols) in skin health care. Both experimental studies (in vivo and in vitro) and clinical trials were included to provide a comprehensive overview of the antioxidant effects. Full-text articles were included to allow for thorough data extraction and analysis. The exclusion criteria for the review paper were as follows: Publications that were not peer-re-viewed, such as editorials, opinion pieces, and non-scholarly articles, were excluded. Articles published in languages other than English were excluded due to potential translation challenges and to maintain consistency. Studies that did not focus on the specified antioxidants or their impact on skin health were excluded. Duplicate publications were excluded to avoid redundancy in the review. Articles with insufficient or incomplete data were excluded to ensure the quality and reliability of the review findings.

Effects of the COVID-19 Pandemic on the Lifestyle and Mental Health of Children in the Puducherry District: A Community-Based Cross-Sectional Study.

INTRODUCTION: The COVID-19 pandemic has tremendously disrupted societal behaviors and norms. People had to cope with new situations, including restrictions on free movement, home confinement, and school closures, among others. With less scope for physical classes, online classes became rampantly common during and after the pandemic. A virtual learning platform cannot replace the societal learning and preparation of children that normally occurs in school settings. The pandemic had a multifaceted impact on children, disrupting their routine work, social life, and mental health. Such uncertain circumstances are bound to interfere with their emotional well-being, with long-term consequences. It is imperative to screen for the effects of the pandemic situation among children for timely action. METHODS: A cross-sectional survey was carried out in both rural and urban areas of Puducherry, India, between February and April 2022, toward the fag end of the pandemic. Face-to-face interviews were conducted among caregivers of 621 children aged 6-17 years. Details such as sociodemographic, personal, and behavioral aspects of the child were collected. Emotional and behavioral difficulties during the pandemic were assessed using the parent (caregiver) version of the Strengths and Difficulties Questionnaire-25 (SDQ-25). Univariate analysis was performed using the chi-square test. Four different regression models were fitted to ascertain the factors influencing the overall difficulty score as well as the SDQ subscales, namely, the internalizing, externalizing, and prosocial scores. A P value of <0.05 was considered significant. RESULTS: Overall, 101 (16.3%) children aged 6-17 years were likely to have emotional and behavioral difficulties according to the SDQ scores. Abnormal externalizing, internalizing, and prosocial scores were documented among 160 (25.8%), 258 (41.5%), and 285 (45.9%) children, respectively. Caregivers reported disruptions in their children's academic performance (426, 68.6%), sleeping patterns (269, 43.3%), and eating habits (256, 41.2%). The use of digital devices for noneducational purposes was reported among 97 (35.9%) children. Younger caregivers (18-45 years), children who used digital devices for >2 hours per day, children who experienced any death due to COVID-19 in their family, and caregivers who perceived that the psychological changes in their children were due to the pandemic were predictors of abnormal SDQ scores. Physical activity for more than two hours per day reduced the risk of emotional and behavioral difficulties in children by 60%. CONCLUSIONS: This research underscores the potential ramifications of the pandemic on the mental well-being and lifestyle of children. Implementing initiatives that promote positive mental health and conducting preventive screening for vulnerable populations, such as children, are considered essential, anticipating the challenges posed by such unprecedented pandemic circumstances in the future.

Process optimization of pearl millet-based fermented beverage components using response surface methodology and evaluation of its physicochemical parameters.

The majority of millets are produced in India, particularly pearl millet, which is more nutritious than both wheat and rice. Native to India, the "north-western semi-arid region" produces rabadi, a natural dairy beverage made from cereal and fermented by lactic acid bacteria. The three components of rabadi viz. pearl millet, buttermilk and deionized water were optimized by using Design Expert software trial version13.0.12.0. Rabadi was processed by using the traditional technique i.e., the three components were mixed in sterile conditions and fermented for 4 h at 37 °C and then cooked for 7-8 min at high flame and finally boiled. Parameters such as pH, viscosity, ash, moisture, total solids, antioxidants, total phenols, tannins, suspension stability, titratable acidity, total sugars, and reducing sugars were analysed for all 16 runs predicted by the software. 6.83 g of pearl millet, 42.44 ml of buttermilk, and 50.72 ml of deionized water were predicted to be the best formulation of rabadi, when using the set goal of maximizing the antioxidants, total phenols and minimizing the tannins. FTIR analysis was also carried out, after the final concentration optimization, to confirm the presence of phenolic compounds, antioxidants, carbohydrates, proteins and fatty acids.

Specific small interfering RNAs (siRNAs) for targeting the metastasis, immune responses, and drug resistance of colorectal cancer cells (CRC).

Colorectal cancer (CRC) involves various genetic alterations, with liver metastasis posing a significant clinical challenge. Furthermore, CRC cells mostly show an increase in resistance to traditional treatments like chemotherapy. It is essential to investigate more advanced and effective therapies to prevent medication resistance and metastases and extend patient life. As a result, it is anticipated that small interfering RNAs (siRNAs) would be exceptional instruments that can control gene expression by RNA interference (RNAi). In eukaryotes, RNAi is a biological mechanism that destroys specific messenger RNA (mRNA) molecules, thereby inhibiting gene expression. In the management of CRC, this method of treatment represents a potential therapeutic agent. However, it is important to acknowledge that siRNA therapies have significant issues, such as low serum stability and nonspecific absorption into biological systems. Delivery mechanisms are thus being created to address these issues. In the current work, we address the potential benefits of siRNA therapy and outline the difficulties in treating CRCby focusing on the primary signaling pathways linked to metastasis as well as genes implicated in the multi-drug resistance (MDR) process.

Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria.

Malaria remains a global health concern as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant Plasmodium falciparum (Pf) parasites revealed point mutations in the Pf_proteasome ß5 active-site (Pfß5). A potent analog (SW584) showed efficacy in a mouse model of human malaria after oral dosing. SW584 had a low propensity to generate resistance (minimum inoculum for resistance [MIR] >109) and was synergistic with dihydroartemisinin. Pf_proteasome purification was facilitated by His8-tag introduction onto ß7. Inhibition of Pfß5 correlated with parasite killing, without inhibiting human proteasome isoforms or showing cytotoxicity. The Pf_proteasome_SW584 cryoelectron microscopy (cryo-EM) structure showed that SW584 bound non-covalently distal from the catalytic threonine, in an unexplored pocket at the ß5/ß6/ß3 subunit interface that has species differences between Pf and human proteasomes. Identification of a reversible, species selective, orally active series with low resistance propensity provides a path for drugging this essential target.

Emergence of imported cutaneous leishmaniasis caused by Leishmania major: a case series from Kerala, India.

Cutaneous leishmaniasis (CL) is often considered a 'great imitator' and is the most common form of leishmaniasis. The Leishmania species responsible for CL varies among countries, as these species exhibit specific distribution patterns. The increased mobility of people across countries has resulted in the imported incidences of leishmaniasis caused by non-endemic species of Leishmania. During 2023, we confirmed three CL cases caused by L. major from Kerala, India, and upon detailed investigation, these were identified to be imported from the Middle East and Kazakhstan regions. This is the first report of CL caused by L. major from Kerala. The lesion morphology, detection of anti-rK 39 antibody and Leishmania parasite DNA from the blood samples were the unique observations of these cases. Kerala, being an emerging endemic zone of visceral leishmaniasis (VL) and CL, the imported incidences of leishmaniasis by non-endemic species can pose a significant threat, potentially initiating new transmission cycles of leishmaniasis caused by non-endemic species.

Emerging roles of long noncoding RNA H19 in human lung cancer.

Lung cancer holds the position of being the primary cause of cancer-related fatalities on a global scale. Furthermore, it exhibits the highest mortality rate among all types of cancer. The survival rate within a span of 5 years is less than 20%, primarily due to the fact that the disease is often diagnosed at an advanced stage, resulting in less effective treatment options compared to earlier stages. There are two main types of primary lung cancer: nonsmall-cell lung cancer, which accounts for approximately 80%-85% of all cases, and small-cell lung cancer, which is categorized based on the specific type of cells in which the cancer originates. The understanding of the biology of this disease and the identification of oncogenic driver alterations have significantly transformed the landscape of therapeutic approaches. Long noncoding RNAs (lncRNAs) play a crucial role in regulating various physiological and pathological processes through diverse molecular mechanisms. Among these lncRNAs, lncRNA H19, initially identified as an oncofetal transcript, has garnered significant attention due to its elevated expression in numerous tumors. Extensive research has confirmed its involvement in tumorigenesis and malignant progression by promoting cell growth, invasion, migration, epithelial-mesenchymal transition, metastasis, and therapy resistance. This comprehensive review aims to provide an overview of the aberrant overexpression of lncRNA H19 and the molecular pathways through which it contributes to the advancement of lung cancer. The findings of this review highlight the potential for further investigation into the diagnosis and treatment of this disease, offering promising avenues for future research.

Modulating a model membrane of sphingomyelin by a tricyclic antidepressant drug.

Tricyclic medicine such as amitriptyline (AMT) hydrochloride, initially developed to treat depression, is also used to treat neuropathic pain, anxiety disorder, and migraines. The mechanism of functioning of this type of drugs is ambiguous. Understanding the mechanism is important for designing new drug molecules with higher pharmacological efficiency. Hence, in the present study, biophysical approaches have been taken to shed light on their interactions with a model cellular membrane of brain sphingomyelin in the form of monolayer and multi-lamellar vesicles. The surface pressure-area isotherm infers the partitioning of a drug molecule into the lipid monolayer at the air water interface, providing a higher surface area per molecule and reducing the in-plane elasticity. Further, the surface electrostatic potential of the lipid monolayer is found to increase due to the insertion of drug molecule. The interfacial rheology revealed a reduction of the in-plane viscoelasticity of the lipid film, which, depends on the adsorption of the drug molecule onto the film. Small-angle X-ray scattering (SAXS) measurements on multilamellar vesicles (MLVs) have revealed that the AMT molecules partition into the hydrophobic core of the lipid membrane, modifying the organization of lipids in the membrane. The modified physical state of less rigid membrane and the transformed electrostatics of the membrane could influence its interaction with synaptic vesicles and neurotransmitters making higher availability of the neurotransmitters in the synaptic cleft.

Detection of Wuchereria bancrofti infection in mosquitoes in areas co-endemic with Brugia malayi in Balasore district, Odisha, India.

Lymphatic filariasis (LF) is a crippling and disfiguring parasitic condition. India accounts for 55% of the world's LF burden. The filarial parasite Wuchereria bancrofti is known to cause 99.4% of the cases while, Brugia malayi accounts for 0.6% of the issue occurring mainly in some pockets of Odisha and Kerala states. The Balasore (Baleswar) district of Odisha has been a known focus of B. malayi transmission. We employed molecular xenomonitoring to detect filarial parasite DNA in vectors. In six selected villages, Gravid traps were used to collect Culex mosquitoes and hand catch method using aspirators was followed for collection of mansonioides. A total of 2903 mosquitoes comprising of Cx. quinquefasciatus (n = 2611; 89.94%), Cx. tritaeniorhynchus (n = 100; 3.44%), Mansonia annuliferea (n = 139; 4.78%) and Mansonia uniformis (n = 53; 1.82%) were collected from six endemic villages. The species wise mosquitoes were made into 118 pools, each with a maximum of 25 mosquitoes, dried and transported to the laboratory at VCRC, Puducherry. The mosquito pools were subjected to parasite DNA extraction, followed by Real-time PCR using LDR and HhaI probes to detect W. bancrofti and B. malayi infections, respectively. Seven pools (6.66%) of Cx. quinquefasciatus, showed infection with only W. bancrofti while none of the pools of other mosquito species showed infection with either W. bancrofti or B. malayi. Although the study area is endemic to B. malayi, none of the vectors of B. malayi was found with parasite infection. This study highlights the ongoing transmission of bancroftian filariasis in the study villages of Balasore district of Odisha and its implications for evaluating LF elimination programme.

Graphene and its hybrid nanocomposite: A Metamorphoses elevation in the field of tissue engineering.

In this discourse, we delve into the manifold applications of graphene-based nanomaterials (GBNs) in the realm of biomedicine. Graphene, characterized by its two-dimensional planar structure, superconductivity, mechanical robustness, chemical inertness, extensive surface area, and propitious biocompatibility, stands as an exemplary candidate for diverse biomedical utility. Graphene include various distinctive characteristics of its two-dimensional planar structure, enormous surface area, mechanical and chemical stability, high conductivity, and exceptional biocompatibility. We investigate graphene and its diverse derivatives, which include reduced graphene oxides (rGOs), graphene oxides (GOs), and graphene composites, with a focus on elucidating the unique attributes relevant to their biomedical utility. In this review article it highlighted the unique properties of graphene, synthesis methods of graphene and functionalization methods of graphene. In the quest for novel materials to advance regenerative medicine, researchers have increasingly turned their attention to graphene-based materials, which have emerged as a prominent innovation in recent years. Notably, it highlights their applications in the regeneration of various tissues, including nerves, skeletal muscle, bones, skin, cardiac tissue, cartilage, and adipose tissue, as well as their influence on induced pluripotent stem cells, marking significant breakthroughs in the field of regenerative medicine. Additionally, this review article explores future prospects in this evolving area of study.

Atypical Dengue Outbreak in Odisha: Insights from the Entomological Investigations.

An outbreak of dengue fever struck Tikarapada village, Rayagada district (April 2020). Among 117 fever cases, 49 tested positive for the dengue NS1 antigen. To identify mosquito-related factors in the outbreak, a survey of 101 houses found Aedes breeding sites in 11.6% of containers. Aedes aegypti (79%) and Aedes albopictus (21%) emerged from collected pupae. The village exhibited high (house index = 24.8), (container index = 11.6), (pupal index = 32.7), and (Breteau index = 40.6) indices. The findings confirmed the presence of Aedes and ample breeding sites, suggesting their role in the outbreak. A report recommending integrated vector control measures was submitted to district and state health authorities.

Toward Malaria Elimination: Understanding Awareness, Prevention, and Health-Seeking Patterns in Odisha, India.

Given India's goal of eliminating malaria by 2030, this study aimed to investigate community perspectives on malaria in highly endemic areas of Odisha, a region historically prone to malaria. The research explores self-reported malaria events, community knowledge, attitudes, practices, health-seeking behaviors, and access to healthcare services. A community-based cross-sectional survey conducted among 387 households between November 2022 and May 2023 served as an extension of our recent project, monitoring malaria elimination efforts in remote and challenging-to-reach communities in Odisha. The participants, who had a mean (SD) age of 41.7 (13.17) years, were predominantly male (88.4%). Self-reported malaria in the last 12 months prior to the survey was 6.2%, with half of the patients opting for primary health centers for treatment, averaging a 5-day recovery per episode. The median cost per malaria treatment episode was U.S. dollars 20.17. A significant majority (79.8%) demonstrated a strong awareness of malaria symptoms and transmission, with 83.3% expressing a favorable attitude toward disease prevention. Notably, 65.1% reported consistent use of long-lasting insecticidal nets. However, nearly half of the participants reported inadequate larval source management and indoor residual spraying services. Although there were slight variations in knowledge, attitude, and practice scores among demographic groups, the overall understanding of and approach to malaria were consistent in the study population, with no statistically significant differences (P >0.05). The study findings offer hope, suggesting that with sustained dedication and focused surveillance, malaria could become a thing of the past.

Stealth Nanocarriers in Cancer Therapy: a Comprehensive Review of Design, Functionality, and Clinical Applications.

Nanotechnology has significantly transformed cancer treatment by introducing innovative methods for delivering drugs effectively. This literature review provided an in-depth analysis of the role of nanocarriers in cancer therapy, with a particular focus on the critical concept of the 'stealth effect.' The stealth effect refers to the ability of nanocarriers to evade the immune system and overcome physiological barriers. The review investigated the design and composition of various nanocarriers, such as liposomes, micelles, and inorganic nanoparticles, highlighting the importance of surface modifications and functionalization. The complex interaction between the immune system, opsonization, phagocytosis, and the protein corona was examined to understand the stealth effect. The review carefully evaluated strategies to enhance the stealth effect, including surface coating with polymers, biomimetic camouflage, and targeting ligands. The in vivo behavior of stealth nanocarriers and their impact on pharmacokinetics, biodistribution, and toxicity were also systematically examined. Additionally, the review presented clinical applications, case studies of approved nanocarrier-based cancer therapies, and emerging formulations in clinical trials. Future directions and obstacles in the field, such as advancements in nanocarrier engineering, personalized nanomedicine, regulatory considerations, and ethical implications, were discussed in detail. The review concluded by summarizing key findings and emphasizing the transformative potential of stealth nanocarriers in revolutionizing cancer therapy. This review enhanced the comprehension of nanocarrier-based cancer therapies and their potential impact by providing insights into advanced studies, clinical applications, and regulatory considerations.

Assessing effects of Cannabis on various neuropathologies: A systematic review.

Natural bioactives possess a wide range of chemical structures that can exert a plethora of pharmacological and toxicological actions, resulting in neuroprotection or neurotoxicity. These pharmacodynamic properties can positively or negatively impact human and animal global healthcare. Remarkably, Ayurvedic botanical Cannabis has been used worldwide by different ethnicities and religions for spiritual, commercial, recreational, nutraceutical, cosmeceutical, and medicinal purposes for centuries. Cannabis-based congeners have been approved by the United States of America's (USA) Food & Drug Administration (FDA) and other global law agencies for various therapeutic purposes. Surprisingly, the strict laws associated with possessing cannabis products have been mitigated in multiple states in the USA and across the globe for recreational use. This has consequently led to a radical escalation of exposure to cannabis-related substances of abuse. However, there is a lacuna in the literature on the acute and chronic effects of Cannabis and its congeners on various neuropathologies. Moreover, in the post-COVID era, there has been a drastic increase in the incidence and prevalence of numerous neuropathologies, leading to increased morbidity and mortality. There is an impending necessity for a safe, economically viable, multipotent, natural bioactive to prevent and treat various neuropathologies. The ayurvedic herb, Cannabis is one of the oldest botanicals known to humans and has been widely used. However, the comprehensive effect of Cannabis on various neuropathologies is not well established. Hence, this review presents effects of Cannabis on various neuropathologies.

A comprehensive insight into the contribution of epigenetics in male infertility; focusing on immunological modifications.

Numerous recent studies have examined the impact epigenetics-including DNA methylation-has on spermatogenesis and male infertility. Differential methylation of several genes has been linked to compromised spermatogenesis and/or reproductive failure. Specifically, male infertility has been frequently associated with DNA methylation abnormalities of MEST and H19 inside imprinted genes and MTHFR within non-imprinted genes. Microbial infections mainly result in male infertility because of the immune response triggered by the bacteria' accumulation of immune cells, proinflammatory cytokines, and chemokines. Thus, bacterially produced epigenetic dysregulations may impact host cell function, supporting host defense or enabling pathogen persistence. So, it is possible to think of pathogenic bacteria as potential epimutagens that can alter the epigenome. It has been demonstrated that dysregulated levels of LncRNA correlate with motility and sperm count in ejaculated spermatozoa from infertile males. Therefore, a thorough understanding of the relationship between decreased reproductive capacity and sperm DNA methylation status should aid in creating new diagnostic instruments for this condition. To fully understand the mechanisms influencing sperm methylation and how they relate to male infertility, more research is required.

Facile synthesis and in silico studies of benzothiazole-linked hydroxypyrazolones targeting α-amylase and α-glucosidase.

Aim: The objective of the present investigation was to design and synthesize new heterocyclic hybrids comprising benzothiazole and indenopyrazolone pharmacophoric units in a single molecular framework targeting α-amylase and α-glucosidase enzymatic inhibition. Materials & methods: 20 new benzothiazole-appended indenopyrazoles, 3a-t, were synthesized in good yields under environment-friendly conditions via cycloaddition reaction, and assessed for antidiabetic activity against α-amylase and α-glucosidase, using acarbose as the standard reference. Results: Among all the hydroxypyrazolones, 3p and 3r showed the best inhibition against α-amylase and α-glucosidase, which finds support from molecular docking and dynamic studies. Conclusion: Compounds 3p and 3r have been identified as promising antidiabetic agents against α-amylase and α-glucosidase and could be considered valuable leads for further optimization of antidiabetic agents.

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