Nuclear Receptor Rev-erbα Role in Fine-Tuning Erythropoietin Gene Expression.

The regulation of RBC homeostasis by erythropoietin (EPO) is critical for O2 transport and maintaining the adequate number of RBCs in vertebrates. Therefore, dysregulation in EPO synthesis results in disease conditions like polycythemia in the case of excessive EPO production and anemia, which occurs when EPO is inadequately produced. EPO plays a crucial role in treating anemic patients; however, its overproduction can increase blood viscosity, potentially leading to fatal heart failure. Consequently, the identification of druggable transcription factors (TFs) and their associated ligands capable of regulating EPO offers a promising therapeutic approach to address EPO-related disorders. This study unveils a novel regulatory mechanism involving two pivotal nuclear receptors (NRs), Rev-erbα and RORα, in the control of EPO gene expression. Rev-erbα acts as a cell-intrinsic negative regulator, playing a vital role in maintaining erythropoiesis at the correct level. It accomplishes this by directly binding to newly identified response elements within the human and mouse EPO gene promoter, thereby repressing EPO production. These findings are further supported by the discovery that a Rev-erbα agonist (SR9011) effectively suppresses hypoxia-induced EPO expression in mice. In contrast, RORα functions as a positive regulator of EPO gene expression, also binding to the same response elements in the promoter to induce EPO production. Finally, the results of this study revealed that the two NRs, Rev-erbα, and RORα, influence EPO synthesis in a negative and positive manner, suggesting that the modulating activity of these two NRs could provide a method to target disorders linked with EPO dysregulation.

Unveiling the phyto-restorative potential of ethereal distillates for atopic dermatitis: an advanced therapeutic approach.

Atopic dermatitis is acknowledged as a vital inflammatory disorder associated with the integumentary system of the body and is characterized by the formation of thick reddish-grey scars and erythema formation on skin, prevalent amidst the populace. Numerous synthetic drugs are available for treatment like antihistamines, immunosuppressants, glucocorticoids etc., but contrarily, essential oil therapy is exclusively lime lighted to favour the purpose. The utilization of available engineered drugs, possess the marked adverse effects owing to prolonged duration of therapy and therefore, essential oils are explored well and proved to exhibit the anti-eczematic, anti-inflammatory and antipruritic properties. Ethereal distillates own the assorted and selective therapeutic properties attributable to presence of bioactive compounds liable to treat this torturous and integumentary disorder, likely lavender oil, patchouli oil, frankincense oil etc., have been found to exert their pharmacological actions by impeding the liberation and action of inflammatory mediators and immunological hyperactivities that are engaged in exacerbating this idiopathic illness. The current attempt provided the update with the aim to bring forth the naturally originated treatment that is pertinent to provide the invulnerable therapy by circumventing the noxious symptoms i.e. erythema formation and inflamed lesions.

Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson's.

Elevated ER stress has been linked to the pathogenesis of several disease conditions including neurodegeneration. In this study, we have holistically determined the differential expression of all the nuclear receptors (NRs) in the presence of classical ER stress inducers. Activation of Nr1h4 and Thrb by their cognate ligands (GW4064 and T3) ameliorates the tunicamycin (TM)-induced expression of ER stress genes. A combination of both ligands is effective in mitigating cell death induced by TM. Further exploration of their protective effects in the Parkinson's disease (PD) model shows that they reduce MPP+-induced dissipation of mitochondrial membrane potential and ROS generation in an in vitro PD model in neuronal cells. Furthermore, the generation of an experimental murine PD model reveals that simultaneous treatment of GW4064 and T3 protects mice from ER stress, dopaminergic cell death, and functional deficits in the MPTP mouse model of PD. Thus, activation of Nr1h4 and Thrb by their respective ligands plays an indispensable role in ER stress amelioration and mounts protective effects in the MPTP mouse model of PD.

Marine-Derived Compounds: A Powerful Platform for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a debilitating form of dementia that primarily affects cholinergic neurons in the brain, significantly reducing an individual's capacity for learning and creative skills and ultimately resulting in an inability to carry out even basic daily tasks. As the elderly population is exponentially increasing, the disease has become a significant concern for society. Therefore, neuroprotective substances have garnered considerable interest in addressing this universal issue. Studies have shown that oxidative damage to neurons contributes to the pathophysiological processes underlying AD progression. In AD, tau phosphorylation and glutamate excitotoxicity may play essential roles, but no permanent cure for AD is available. The existing therapies only manage the early symptoms of AD and often come with numerous side effects and toxicities. To address these challenges, researchers have turned to nature and explored various sources such as plants, animals, and marine organisms. Many historic holy books from different cultures emphasize that adding marine compounds to the regular diet enhances brain function and mitigates its decline. Consequently, researchers have devoted significant time to identifying potentially active neuroprotective substances from marine sources. Marine-derived compounds are gaining recognition due to their abundant supply of diverse chemical compounds with biological and pharmacological potential and unique mechanisms of action. Several studies have reported that plants exhibit multitarget potential in treating AD. In light of this, the current study focuses on marine-derived components with excellent potential for treating this neurodegenerative disease.

Exploring the Intersection of Geophysics and Diagnostic Imaging in the Health Sciences.

To develop diagnostic imaging approaches, this paper emphasizes the transformational potential of merging geophysics with health sciences. Diagnostic imaging technology improvements have transformed the health sciences by enabling earlier and more precise disease identification, individualized therapy, and improved patient care. This review article examines the connection between geophysics and diagnostic imaging in the field of health sciences. Geophysics, which is typically used to explore Earth's subsurface, has provided new uses of its methodology in the medical field, providing innovative solutions to pressing medical problems. The article examines the different geophysical techniques like electrical imaging, seismic imaging, and geophysics and their corresponding imaging techniques used in health sciences like tomography, magnetic resonance imaging, ultrasound imaging, etc. The examination includes the description, similarities, differences, and challenges associated with these techniques and how modified geophysical techniques can be used in imaging methods in health sciences. Examining the progression of each method from geophysics to medical imaging and its contributions to illness diagnosis, treatment planning, and monitoring are highlighted. Also, the utilization of geophysical data analysis techniques like signal processing and inversion techniques in image processing in health sciences has been briefly explained, along with different mathematical and computational tools in geophysics and how they can be implemented for image processing in health sciences. The key findings include the development of machine learning and artificial intelligence in geophysics-driven medical imaging, demonstrating the revolutionary effects of data-driven methods on precision, speed, and predictive modeling.

Understanding the promising role of antibody drug conjugates in breast and ovarian cancer.

A nascent category of anticancer therapeutic drugs called antibody-drug conjugates (ADCs) relate selectivity of aimed therapy using chemotherapeutic medicines with high cytotoxic power. Progressive linker technology led to the advancement of more efficacious and safer treatments. It offers neoteric as well as encouraging therapeutic strategies for treating cancer. ADCs selectively administer a medication by targeting antigens which are abundantly articulated on the membrane surface of tumor cells. Tumor-specific antigens are differently expressed in breast and ovarian cancers and can be utilized to direct ADCs. Compared to conventional chemotherapeutic drugs, this approach enables optimal tumor targeting while minimizing systemic damage. A cleavable linker improves the ADCs because it allows the toxic payload to be distributed to nearby cells that do not express the target protein, operating on assorted tumors with dissimilar cell aggregation. Presently fifteen ADCs are being studied in breast and ovarian carcinoma preclinically, and assortment of few have already undergone promising early-phase clinical trial testing. Furthermore, Phase I and II studies are investigating a wide variety of ADCs, and preliminary findings are encouraging. An expanding sum of ADCs will probably become feasible therapeutic choices as solo agents or in conjunction with chemotherapeutic agents. This review accentuates the most recent preclinical findings, pharmacodynamics, and upcoming applications of ADCs in breast and ovarian carcinoma.

Bioactive Compound-Loaded Nanocarriers for Hair Growth Promotion: Current Status and Future Perspectives.

Hair loss (alopecia) has a multitude of causes, and the problem is still poorly defined. For curing alopecia, therapies are available in both natural and synthetic forms; however, natural remedies are gaining popularity due to the multiple effects of complex phytoconstituents on the scalp with fewer side effects. Evidence-based hair growth promotion by some plants has been reported for both traditional and advanced treatment approaches. Nanoarchitectonics may have the ability to evolve in the field of hair- and scalp-altering products and treatments, giving new qualities to hair that can be an effective protective layer or a technique to recover lost hair. This review will provide insights into several plant and herbal formulations that have been reported for the prevention of hair loss and stimulation of new hair growth. This review also focuses on the molecular mechanisms of hair growth/loss, several isolated phytoconstituents with hair growth-promoting properties, patents, in vivo evaluation of hair growth-promoting activity, and recent nanoarchitectonic technologies that have been explored for hair growth.

Evolving Advances in the Cosmetic Use of Probiotics and Postbiotics: Health, Regulatory and Marketing Aspects.

Ongoing development in cosmetics is increasingly making use of probiotics, which are defined as "live microorganisms with health-enhancing properties mediated through ingestion or topical application to the host". The observation that several bacterial strains augment normal processes of healthy tissue maintenance, particularly for the skin, has opened up new avenues for the use of bacterial strains in cosmetics. A principal feature of such "cosmeceuticals" is an application of increasing insight into the biochemical nature of the skin's normal microbial flora, also called its microbiome. The opportunity of manipulating the skin microbiome to address various skin disorders has revealed novel routes for treatment. The skin microbiome manipulation approaches to address various skin disorders include skin microbiome transplantation, skin bacteriotherapy, and prebiotic stimulation. Research in this field has revealed that medical outcome-targeted manipulation of skin microbiome bacterial strain makeup may significantly increase skin health and appearance. Commercial availability of probiotic skincare products is rapidly expanding worldwide due to satisfactory laboratory results and public perception of probiotics as being intrinsically more wholesome than other bioactive substances, such as synthetics. Major outcomes of probiotic use include a significant reduction in skin wrinkling, acne and other conditions adversely affecting skin appearance and healthy function. Moreover, probiotics may additionally promote normal skin hydration, resulting in a vibrant and lustrous appearance. Nevertheless, significant technical challenges remain for the full optimization of probiotics in cosmetic products. This article summarizes the evolving nature of this field and explores current probiotic research initiatives, along with regulatory aspects and significant challenges in the manufacturing of cosmetics in the context of market expansion for these products.

Effect of Normal Saline versus PlasmaLyte on Coagulation and Metabolic Status in Patients Undergoing Neurosurgical Procedures.

Background The choice of intraoperative fluid in neurosurgical patients is important as we need to maintain adequate cerebral perfusion and oxygenation and also avoid cerebral edema. Normal saline (NS) is commonly used in neurosurgeries, but it leads to hyperchloremic metabolic acidosis, which may result in coagulopathy. Balanced crystalloid with physiochemical composition akin to that of plasma has favorable effects on metabolic profile and may avoid the problems associated with NS. Against this background, the present study aimed to compare the effects of NS versus PlasmaLyte (PL) on coagulation profile in patients undergoing neurosurgical procedures. Methods This prospective, randomized, double-blinded study was conducted in 100 adult patients scheduled to undergo various neurosurgical procedures. Patients were randomly allocated in two groups of 50 each to receive either NS or PL intraoperatively and postoperatively till 4 hours after the surgery. Hemoglobin, hematocrit, coagulation profile (PT, PTT, and INR), serum chloride, pH, blood urea, and serum creatinine were measured prior to induction (baseline) and 4 hours after completion of surgery. Results Demographic characteristics were statistically similar between the two groups. Coagulation profile parameters were comparable between the two groups at baseline as well as 4 hours after surgery. pH was significantly lower in the NS group as compared to the PL group at 4 hours after surgery. Postoperatively blood urea, serum creatinine, and serum chloride levels were significantly raised in the NS group as compared to the PL group. Hemoglobin and hematocrit values were similar between the two groups. Conclusion Coagulation profile parameters were normal and statistically similar with intraoperative infusion of NS versus PL in patients undergoing neurosurgical procedures. However, use of PL was associated with a better acid-base and renal profile in these patients.

Alkaloids as Potential Anti-HIV Agents.

BACKGROUND: Alkaloids are nitrogen-containing compounds that are naturally occurring and have a variety of biological activities, including antimicrobial properties. In this study, the authors used a molecular docking approach to evaluate the anti-HIV potential of 64 alkaloids. METHODS: The authors used the Molegro Virtual Docker software to dock the alkaloids into the active sites of three HIV enzymes: protease, integrase, and non-nucleoside reverse transcriptase (NNRT). The docking scores were used to assess the potential of the alkaloids to inhibit the enzymes. RESULTS: The results showed the alkaloids to have good potential to inhibit the enzymes. Tubocurarine and reserpine were found to be the most potent alkaloids, with docking scores of -123.776 and - 114.956, respectively. CONCLUSION: The authors concluded that tubocurarine and reserpine could be further promoted as potential lead molecules for the development of new anti-HIV drugs.

White Coat Effect: Is It Because of the Hospital Setting, or Is It Physician-Induced?

INTRODUCTION: White coat hypertension (WCH) patients are those individuals who have high blood pressure (BP) in the medical environment but are normal during their daily activities. White coat hypertensive patients with normal daytime ambulatory blood pressure monitoring (ABPM) rapidly progress to sustained hypertension. WCH is mainly treated with non-pharmacological methods. Alpha-1 agonists and beta blockers are logical treatment choices for patients with fixed hypertension with the White Coat Effect (WCE). Masked hypertension patients are those individuals who have normal values at the doctor's office but elevated BP at home or during 24-hour ABPM (24-hour or daytime). ABPM is a more practical and reliable method for detecting patients with WCH. MATERIAL AND METHODS: This observational study was conducted at Dayanand Medical College & Hospital, Ludhiana, over the course of one year (December 2015 to November 2016). The primary objective of the study was to determine whether there was a difference in blood pressure readings between the home setting and the hospital setting. The secondary objective was to determine whether the difference, if present, between the hospital and home readings was due to the hospital setting, physician presence, or a combination of both. Patients with stage 1 hypertension were included in the study, irrespective of antihypertensive treatment. Patients with ischemic heart disease, chronic liver failure, and chronic kidney disease who could not follow protocol instructions were excluded. RESULTS: In our study, the mean age of patients was 53.91±12.86 years. The patient's mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) readings at the hospital were higher than their home readings (p-0.012; p-0.001, respectively). Mean hospital SBP and DBP readings recorded by the physician were higher than readings recorded by patients alone at home (p-0.002; p-0.014, respectively) and alone at the hospital (p-0.004; p-0.001, respectively). BP readings taken by the physician with a manual sphygmomanometer were significantly lower than those taken with a digital sphygmomanometer by patients and physicians in all settings (p<0.05). The mean rise in BP was significant in both the physician's presence and the hospital environment (p<0.05 for both), and this rise was more significantly associated with the hospital effect than the physician effect (p<0.05). CONCLUSION: Misdiagnosis of hypertension results in inappropriate prescription and overuse of antihypertensive medications for individuals who are not persistently hypertensive. So it is very important to rule out WCH in both the hospital setting and the physician's presence, more precisely by ABPM. WCH can be diagnosed with regular BP monitoring by a digital sphygmomanometer at home.

Role of Routine Blood Parameters in Predicting Mortality Among Surgical Patients With Sepsis.

BACKGROUND: Outcome prediction for surgical patients with sepsis may be conducive to early aggressive interventions. In several studies, changes in the level of numerous biomarkers like red cell distribution width (RDW), platelet count (PC), mean platelet volume (MPV), and platelet distribution width (PDW) have been demonstrated to be associated with mortality in critically ill patients. We aimed at investigating the prognostic significance of dynamic changes in RDW, PC, MPV, and PDW in surgical patients with sepsis. METHODS: We prospectively enrolled 110 surgical patients of sepsis in our study admitted to the surgical ward and ICU. We measured RDW, PC, MPV, and PDW on days 1, day 4, and day 8. Receiver operating characteristics (ROC) were generated for prognostic validation of these parameters and mortality in surgical patients with sepsis.  Results: We found that higher RDW and PDW on day 1 among non-survivors as compared to survivors on day 1 were significantly associated with mortality. ROC curves showed that RDW and PDW on day 1 could be used to predict mortality in surgical patients with sepsis and it was dynamic changes in PC on day 4 and day 8 along with a change in MPV on day 8, which was significantly associated with mortality. CONCLUSION: The major findings of our study were baseline value of RDW and PDW on day 1 and continuous decrease in PC and increase in MPV over one week were significantly associated with mortality. So, it is better to monitor dynamic changes in PC and MPV in combination with baseline RDW and PDW. So, these parameters can be promising markers to assess prognosis in surgical patients with sepsis.

Risk Factors and Outcome Analysis of Gram-Positive Bacteremia in Critically Ill Patients.

Introduction Bloodstream infection (BSI) is a common problem for patients in the intensive care unit (ICU). Nearly 60% of primary bloodstream infections are caused by Gram-positive cocci. Gram-positive bacteria gain access to the bloodstream through invasive procedures and various patient care equipment like catheters, intravenous lines, and mechanical ventilators. S. aureus is considered to be the major cause of septicemia. Knowledge of healthcare-associated infections and the antimicrobial susceptibility patterns of the isolates are crucial in guiding empirical treatment. Methods This prospective observational study was conducted in Medical ICU, Dayanand Medical College & Hospital, Ludhiana over a period of one year (December 2015 to November 2016). Patients whose blood cultures tested positive for Gram-positive bacteria were included in the study. This study was carried out to assess the implications and risk factors for nosocomial BSI and several factors, including the age of the patient, the severity of illness, the presence of catheters, and the microorganisms causing the BSI to independently predict mortality. Chief complaints and risk factors were evaluated. APACHE-II scores were calculated for all patients and outcomes were analyzed. Results In our study, the mean age of patients was 50.93±14.09 years. Central line insertion was found as the most common risk factor (58.7%). A statistically significant correlation was obtained between APACHE-II scores and the presence of risk factors i.e. central line insertion (p-value=0.010) and diabetes mellitus (p-value=0.003). The most common Gram-positive pathogen isolated by blood culture was methicillin-sensitive S. aureus (44.2%). For management, the majority of the patients were prescribed teicoplanin (58.7%). The 28-day overall mortality rate in our study was 52.9%. Conclusion We conclude that independent risk factors like diabetes mellitus, central line insertion, and acute pancreatitis in adult patients with Gram-positive bacteremia were associated with higher mortality. We have also concluded that the administration of early appropriate antibiotics improves patient outcomes.

Financing for Sustainable Development Goals (SDGs) in the Era of COVID-19 and Beyond.

The economic and social impact of covid-19 pandemic both on developing and developed countries has been significant. In addition to the impact of the pandemic, the current Ukraine war has also led to severe supply chain disruptions leading to a sharp increase in food and commodity prices globally. Due to a combination of external shocks and the impact of the pandemic global economic growth is expected to slow down from 6.1% in 2021 to 3.2% in 2022 and further to 2.7% in 2023 (IMF in: World economic outlook, International Monetary Fund, 2022). The above factors have led to a sharp increase in government expenditure constraining both developed and developing countries' fiscal capacity. This has further implications for the achievement of SDGs especially for low-income countries. The challenge for developing countries in the current scenario is to mobilise adequate resources both from domestic and international sources, not just for the achievement of SDGs as such, but also to sustain the livelihoods, health, and welfare of people. This special issue aims to examine some of these issues in the context of developing countries.

L'impact économique et social de la pandémie de COVID-19, tant sur les pays en développement que sur les pays développés, a été important. Outre l'impact de la pandémie, la guerre actuelle en Ukraine a également entraîné de graves perturbations de la chaîne d'approvisionnement, entraînant une forte augmentation des prix des denrées alimentaires et des matières premières dans le monde. En raison d'une combinaison entre chocs externes et impact de la pandémie, la croissance économique mondiale devrait ralentir de 6,1 % en 2021 à 3,2 % en 2022, puis à 2,7 % en 2023 (FMI 2022). Les facteurs ci-dessus ont conduit à une forte augmentation des dépenses publiques, limitant la capacité budgétaire des pays développés et en développement. Cela a d'autres implications pour la réalisation des ODD, en particulier pour les pays à faible revenu. Le défi pour les pays en développement dans le scénario actuel est de mobiliser des ressources adéquates provenant de sources nationales et internationales, non seulement pour la réalisation des ODD en tant que tels, mais aussi pour maintenir les moyens de subsistance, la santé et le bien-être des personnes. Ce numéro spécial vise à aborder certaines de ces questions dans le contexte des pays en développement.

Association of PD-L1 and p16 expression with clinicopathological parameters in oral cavity and oropharyngeal squamous cell carcinoma.

BACKGROUND: High expression of PD-L1 in tumour cells is associated with a higher response rate to immune checkpoint inhibitors, which target T regulatory pathways. p16 is a surrogate marker for human papilloma virus associated cancers. The present study was conducted to evaluate PD-L1 and p16 expression in head and neck squamous cell carcinomas and its correlation with clinicopathological parameters. MATERIALS AND METHODS: Histologically confirmed cases of head and neck squamous cell carcinomas were evaluated for PD-L1 and p16 expression along with its correlation with grade and site of the tumour. RESULTS: Out of 40 cases, 21 (52.5 %) showed positive immunoreactivity for PD-L1 while 13 (32.5 %) were positive for p16. A significant association was observed between PD-L1 and p16 expression in the oropharynx (p value= 0.035). No significant association could be established between clinicopathological parameters and PD-L1/ p16 expression or between PD-L1 and p16 in the oral cavity. CONCLUSION: PD-L1 expression shows a positive association with p16 in oropharyngeal squamous cell carcinomas. Immune checkpoint inhibitors against PD-L1 can be used in carcinomas with positive expression for PD-L1.

Angiogenic footprints in diabetic retinopathy: opportunities for drug development.

Diabetic retinopathy is one of the withering disorders that has been making the lives of patients miserable. Arising as a result of chronic high blood sugar levels in diabetes patients, retinopathy has become a major reason causing permanent blindness, retinal detachment, vitreous humor, rage, or glaucoma among patients. Angiogenesis being the major culprit behind the development of this condition is the growth of new blood vessels from the earlier ones existing. The abnormal growth and poor development of blood vessels also lead to aggravation of the conditions, with vascular endothelial growth factor (VEGF) playing a major role in the process. Various anti-angiogenic therapies or anti-VEGF therapies are being explored for the treatment of this condition. 4 widely explored drugs being-Bevacizumab, pegaptanib sodium, ranibizumab, and aflibercept. The review article tries to summarize studies illustrating the efficacy of these drugs in the treatment of diabetic retinopathy along with some of the herbal therapeutic paradigms displaying anti-angiogenic action that is being used to treat this condition.

A Comparative Study of Intravenous Dexmedetomidine with Local Infiltration of Ropivacaine in Attenuation of Stress Response to Skull Pin Insertion in Craniotomies.

Objective Skull pin insertion in patients undergoing craniotomies elicits hemodynamic and neuroendocrine stress response that may be deleterious to the patient. Various drugs and techniques have been documented in literature to abate this stress response. Against this background, we aimed to compare the efficacy of intravenous dexmedetomidine and local infiltration of ropivacaine for attenuation of stress response to pin insertion in craniotomies. Methods Eighty-eight adult patients undergoing craniotomy under general anesthesia from March 2019 to April 2020 requiring application of head holder were randomized into two equal groups. After intubation, 0.75 µg kg -1 of dexmedetomidine over 10 minutes through infusion was given in group D, while local infiltration at pin sites was done with 0.5% ropivacaine, 2 mL at each site in group R. Hemodynamic parameters and levels of serum cortisol, prolactin, and blood glucose were measured before and after pin insertion. Unpaired t -test for continuous variables and Mann-Whitney U test was used for nonnormally distributed variables. Results Heart rate was statistically similar between the two groups at all the observed time points. The difference in mean arterial pressure values between the two groups was found to be statistically significant only from 10 to 20 minutes after pin insertion being statistically similar at rest of the time points. Levels of serum glucose, cortisol, and prolactin values 30 minutes after pin insertion were statistically similar between both groups. Conclusion We concluded that both interventions are equally efficacious in attenuation of hemodynamic and stress response to head holder application in patients undergoing craniotomies.

Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation.

Nuclear receptors are a unique family of transcription factors that play cardinal roles in physiology and plethora of human diseases. The adopted orphan nuclear receptor Nr1d1 is a constitutive transcriptional repressor known to modulate several biological processes. In this study, we found that Nr1d1 plays a decisive role in T helper (Th)-cell polarization and transcriptionally impedes the formation of Th2 cells by directly binding to the promoter region of GATA binding protein 3 (GATA3) gene. Nr1d1 interacts with its cellular companion, the nuclear receptor corepressor and histone deacetylase 3 to form a stable repression complex on the GATA3 promoter. The presence of Nr1d1 also imparts protection against associated inflammatory responses in murine model of asthma and its ligand SR9011 eased disease severity by suppressing Th2 responses. Moreover, Chip-seq profiling uncovered Nr1d1 interactions with other gene subsets that impedes Th2-linked pathways and regulates metabolism, immunity and brain functions, therefore, providing empirical evidence regarding the genetic link between asthma and other comorbid conditions. Thus, Nr1d1 emerges as a molecular switch that could be targeted to subdue asthma.

Natural Products as Sources of Multitarget Compounds: Advances in the Development of Ferulic Acid as Multitarget Therapeutic.

Nature has provided therapeutic substances for millennia, with many valuable medications derived from plant sources. Multitarget drugs become essential in the management of various disorders, including hepatic disorders, neurological disorders, diabetes, and carcinomas. Ferulic acid is a significant potential therapeutic agent, which is easily available at low cost, possesses a low toxicity profile, and has minimum side effects. Ferulic acid exhibits various therapeutic actions by modulation of various signal transduction pathways such as Nrf2, p38, and mTOR. The actions exhibited by ferulic acid include anti-apoptosis, antioxidant, anti-inflammatory, antidiabetic, anticarcinogenic, hepatoprotection, cardioprotection, activation of transcriptional factors, expression of genes, regulation of enzyme activity, and neuroprotection, which further help in treating various pathophysiological conditions such as cancer, skin diseases, brain disorders, diabetes, Parkinson's disease, Alzheimer's disease, hypoxia, hepatic disorders, H1N1 flu, and viral infections. The current review focuses on the significance of natural products as sources of multitarget compounds, and a primary focus has been made on ferulic acid and its mechanism, role, and protective action in various ailments.

Rotavirus Strain Distribution before and after Introducing Rotavirus Vaccine in India.

In April 2016, an indigenous monovalent rotavirus vaccine (Rotavac) was introduced to the National Immunization Program in India. Hospital-based surveillance for acute gastroenteritis was conducted in five sentinel sites from 2012 to 2020 to monitor the vaccine impact on various genotypes and the reduction in rotavirus positivity at each site. Stool samples collected from children under 5 years of age hospitalized with diarrhea were tested for group A rotavirus using a commercial enzyme immunoassay, and rotavirus strains were characterized by RT-PCR. The proportion of diarrhea hospitalizations attributable to rotavirus at the five sites declined from a range of 56-29.4% in pre-vaccine years to 34-12% in post-vaccine years. G1P[8] was the predominant strain in the pre-vaccination period, and G3P[8] was the most common in the post-vaccination period. Circulating patterns varied throughout the study period, and increased proportions of mixed genotypes were detected in the post-vaccination phase. Continuous long-term surveillance is essential to understand the diversity and immuno-epidemiological effects of rotavirus vaccination.