Evaluation of Moringa Oleifera Leaf Extract for its In vitro Antibacterial Properties, Mechanism of Action, and In vivo Corneal Ulcer Healing Effects in Rabbits' Eyes.

M. oleifera is the most adapted tree species in different medicinal eco-systems and has resilience against climate changes. This multiple-use tree provides healthy foods, snacks, honey, and fuel. Besides this, it has immense promising applicationsby offering antimicrobial and antibacterial activities for targeted uses. This validates the court of Hippocrates that let food be the medicine and medicine be the food for which moringa qualifies. In view of this, the antioxidant and in vitro antibacterial potency of the hydro-ethanolic extract of M. oleifera was evaluated on clinically isolated multidrug-resistant strains of Staphylococcus aureus. Furthermore, in vivo, the healing response of M. oleifera extract was analysed on corneal ulcers induced in rabbit eyes infected with methicillin-resistant Staphylococcus aureus. TheM. oleifera extract exhibited exponential antioxidant activity. In-vitro antibacterial activity was evaluated by agar well diffusion assay showing zone of inhibition ranging from 11.05±0.36 to 20±0.40 mm at concentrations of 20, 40, 80, and 160 mg/ml, whereas, in our finding, no zone of inhibition was observed below 20 mg/ml concentration, which indicated that there is threshold limit below which the antibacterial activity of M. oleifera extract is not observed. Furthermore, continuous application of 3% and 5% M. oleifera extract (eye drop) four times a day for 14 consecutive days showed a significant healing response of the eyes of rabbits with corneal ulcers. These results suggest that M. oleifera extract could be a viable alternative to existing antibacterial therapies for corneal ulcers. Additionally, there is a possibility of commercial formulation of M. oleifera extract in the form of deliverable pharmaceutical products; therefore, it should be explored further.

Exploring the Potential Benefits of Bovine Colostrum Supplementation in the Management of Diabetes and Its Complications: A Comprehensive Review.

Diabetes is a metabolic illness marked by elevated levels of glucose in the bloodstream due to the inadequate production or use of insulin in the body. Diabetes can result in a range of consequences, with the most prevalent being cardiovascular disease, renal failure, vision loss, and limb removal. Natural compounds isolated from different sources, like colostrum, are the most important compounds for the treatment of diabetes. Colostrum is a form of lactation produced by mammals in the first days after giving birth to their offspring, having a rich source of constituents and showing multipharmacological properties. This review was prepared on the basis of a variety of authoritative search databases, including Google Scholar, Scopus, and PubMed. In addition, the publications and other online sources were also included. In the literature search, the terms "colostrum," "diabetes," "uses," "management," "constituent," "composition," "alternative sources," "mechanism of action," "preclinical," "clinical," "marketed formulations," and "patents" were utilized as keywords and collected from last two decades. Colostrum has been utilized as a treatment for a wide variety of illnesses due to its active constituents. A variety of colostrums are available in the market, like goat colostrum, porcine colostrum, sheep colostrum, human colostrum and many more. They have the full potential of nutrients like minerals, vitamins, lactose, essential enzymes, proteins and high concentrations of immunoproteins. Mostly, the colostrums are used for treating diabetes and its complications. Preclinical and clinical studies of metabolic syndrome, especially on diabetes and its complications, were also reported at the National and International levels, which evidently prove that the use of colostrums in the long term can be beneficial for various ailments associated with diabetes. In general, the findings of this review indicate that supplementation with colostrum may hold promise as a novel therapeutic intervention for people who have diabetes and its complications; however, additional research is required to fully understand its mechanisms of action and determine the best possible dosage as well as the time period of supplementation.

Assessment of the mechanistic role of an Indian traditionally used ayurvedic herb Bacopa monnieri (L.)Wettst. for ameliorating oxidative stress in neuronal cells.

ETHNOPHARMACOLOGICAL RELEVANCE: This study has important ethnopharmacological implications since it systematically investigated the therapeutic potential of Bacopa monnieri(L.) Wettst. (Brahmi) in treating neurological disorders characterized by oxidative stress-a growing issue in the aging population. Bacopa monnieri, which is strongly rooted in Ayurveda, has long been recognized for its neuroprotective and cognitive advantages. The study goes beyond conventional wisdom by delving into the molecular complexities of Bacopa monnieri, particularly its active ingredient, Bacoside-A, in countering oxidative stress. The study adds to the ethnopharmacological foundation for using this herbal remedy in the context of neurodegenerative disorders by unravelling the scientific underpinnings of Bacopa monnieri's effectiveness, particularly at the molecular level, against brain damage and related conditions influenced by oxidative stress. This dual approach, which bridges traditional wisdom and modern investigation, highlights Bacopa monnieri's potential as a helpful natural remedy for oxidative stress-related neurological diseases. AIM OF THE STUDY: The aim of this study is to investigate the detailed molecular mechanism of action (in vitro, in silico and in vivo) of Bacopa monnieri (L.) Wettst. methanolic extract and its active compound, Bacoside-A, against oxidative stress in neurodegenerative disorders. MATERIALS AND METHODS: ROS generation activity, mitochondrial membrane potential, calcium deposition and apoptosis were studied through DCFDA, Rhodamine-123, FURA-2 AM and AO/EtBr staining respectively. In silico study to check the effect of Bacoside-A on the Nrf-2 and Keap1 axis was performed through molecular docking study and validated experimentally through immunofluorescence co-localization study. In vivo antioxidant activity of Bacopa monnieri extract was assessed by screening the oxidative stress markers and stress-inducing hormone levels as well as through histopathological analysis of tissues. RESULTS: The key outcome of this study is that the methanolic extract of Bacopa monnieri (BME) and its active component, Bacoside-A, protect against oxidative stress in neurodegenerative diseases. At 100 and 20 µg/ml, BME and Bacoside-A respectively quenched ROS, preserved mitochondrial membrane potential, decreased calcium deposition, and inhibited HT-22 mouse hippocampus cell death. BME and Bacoside-A regulated the Keap1 and Nrf-2 axis and their downstream antioxidant enzyme-specific genes to modify cellular antioxidant machinery. In vivo experiments utilizing rats subjected to restrained stress indicated that pre-treatment with BME (50 mg/kg) downregulated oxidative stress markers and stress-inducing hormones, and histological staining demonstrated that BME protected the neuronal cells of the Cornu Ammonis (CA1) area in the hippocampus. CONCLUSIONS: Overall, the study suggests that Bacopa monnieri(L.) Wettst. has significant potential as a natural remedy for neurodegenerative disorders, and its active compounds could be developed as new drugs for the prevention and treatment of oxidative stress-related diseases.

Insights into Prospects of Novel NSAID Prodrugs in the Management of Gastrointestinal Toxicity: A Perspective Review.

Non-steroidal anti-inflammatory drugs (NSAIDs) have a long history in the healthcare system due to their therapeutic potential. These NSAIDs cause ulcerogenicity, stomach pains, gastrointestinal hemorrhage, mucosa bleeding, and pancreatitis when used moderately and consistently. With researchers, managing the aforementioned adverse effects therapeutically is getting increasingly difficult. One method for creating NSAID moieties with low penetration as well as ulcerogenic properties is the prodrug technique. During the oral consumption of NSAID-prodrugs, ulcerations, intestinal hemorrhage, and mucosa hemorrhage have significantly decreased. Considering this background, this review focussed on NSAID prodrugs as well as their justifications, the pathogenesis of NSAIDs inducing gastrointestinal toxicity, and the role of different antioxidants and spacer groups. Prodrug moieties have more advantages over parent medicines concerning both solubility and lipophilicity. In general, NSAID-class prodrugs can successfully treat both acute and long-term inflammation and aches without causing ulcerotoxicity and related gastrointestinal side effects, which reduces their burden from the pharmacoeconomic perspective.

Unravelling the Crosstalk between Estrogen deficiency and Gut-biota Dysbiosis in the development of Diabetes Mellitus.

Estrogens are classically considered essential hormonal signals, but they exert profound effects in a number of physiological and pathological states, including glucose homeostasis and insulin resistance. Estrogen deficiency after menopause in most women leads to increased androgenicity and changes in body composition, and it is recommended to manipulate the ß-cell function of the pancreas, insulin-induced glucose transport, and hepatic glucose output, hence, the increasing incidence of type 2 diabetes mellitus. Recently, studies have reported that gut biota alteration due to estrogen deficiency contributes to altered energy metabolism and, hence, accentuates the pathology of diabetes mellitus. Emerging research suggests estrogen deficiency via genetic disposition or failure of ovaries to function in old age modulates the insulin resistance and glucose secretion workload on pancreatic beta cells by decreasing the levels of good bacteria such as Akkermansia muciniphila, Bifidobacterium spp., Lactobacillus spp., Faecalibacterium prausnitzii, Roseburia spp., and Prevotella spp., and increasing the levels of bad bacteria's such as Bacteroides spp., Clostridium difficile, Escherichia coli, and Enterococcus spp. Alteration in these bacteria's concentrations in the gut further leads to the development of impaired glucose uptake by the muscles, increased gluconeogenesis in the liver, and increased lipolysis and inflammation in the adipose tissues. Thus, the present review paper aims to clarify the intricate interactions between estrogen deficiency, gut microbiota regulation, and the development of diabetes mellitus.

Convection-enhanced Diffusion: A Novel Tactics to Crack the BBB.

Although the brain is very accessible to nutrition and oxygen, it can be difficult to deliver medications to malignant brain tumours. To get around some of these issues and enable the use of therapeutic pharmacological substances that wouldn't typically cross the blood-brain barrier (BBB), convection-enhanced delivery (CED) has been developed. It is a cutting-edge strategy that gets beyond the blood-brain barrier and enables targeted drug administration to treat different neurological conditions such as brain tumours, Parkinson's disease, and epilepsy. Utilizing pressure gradients to spread the medicine across the target area is the main idea behind this diffusion mechanism. Through one to several catheters positioned stereotactically directly within the tumour mass, around the tumour, or in the cavity created by the resection, drugs are given. This method can be used in a variety of drug classes, including traditional chemotherapeutics and cutting-edge investigational targeted medications by using positive-pressure techniques. The drug delivery volume must be optimized for an effective infusion while minimizing backflow, which causes side effects and lowers therapeutic efficacy. Therefore, this technique provides a promising approach for treating disorders of the central nervous system (CNS).

Effect of Vitamin D on Retinoblastoma Protein in Prediabetic Individuals.

About 50.8 million people were diagnosed with diabetes in 2011; the count has increased by 10 million in the last five years. Type-1 diabetes could occur at any age, but predominantly in children and young adults. The risk of developing type II diabetes mellitus in the offspring of parents with DM II is 40% if one parent has DM II and approaches 70% if both parents have DM II. The process of developing diabetes from normal glucose tolerance is continuous, with insulin resistance being the first stage. As prediabetes progresses slowly to DM II, it may take approximately 15-20 years for an individual to become diabetic. This progression can be prevented or delayed by taking some precautions and making some lifestyle amendments, e.g., reducing weight by 5-7% of total body weight if obese, etc. Retinoblastoma protein is one of the pocket proteins that act as crucial gatekeepers during the G1/S transition in the cell cycle. A loss or defect in single- cell cycle activators (especially CDK4 and CDK6) leads to cell failure. In diabetic or stress conditions, p53 becomes a transcription factor, resulting in the transactivation of CKIs, which leads to cell cycle arrest, cell senescence, or cell apoptosis. Vitamin D affects insulin sensitivity by increasing insulin receptors or the sensitivity of insulin receptors to insulin. It also affects peroxisome proliferator-activated receptors (PPAR) and extracellular calcium. These influence both insulin resistance and secretion mechanisms, undertaking the pathogenesis of type II diabetes. The study confines a marked decrement in the levels of random and fasting blood glucose levels upon regular vitamin D intake, along with a significant elevation of retinoblastoma protein levels in the circulatory system. The most critical risk factor for the occurrence of the condition came out to be family history, showing that patients with first-degree relatives with diabetes are more susceptible. Factors such as physical inactivity or comorbid conditions further aggravate the risk of developing the disease. The increase in pRB levels caused by vitamin D therapy in prediabetic patients directly influences blood glucose levels. pRB is supposed to play a role in maintaining blood sugar levels. The results of this study could be used for further studies to evaluate the role of vitamin D and pRB in regeneration therapy for beta cells in prediabetics.

Evaluation of Iris Kashmiriana Baker plant extracts against nociception and rheumatoid arthritis in experimental rats: A concept proof by In-silico model.

ETHNOPHARMACOLOGICAL RELEVANCE: Iris Kashmiriana Baker, a traditional medicinal plant, is native to Asia, found in India, Nepal, Afghanistan, Pakistan, as name indicates majorly it's found in Kashmir region of India. Ethnopharmacologically this plant has been used there for the management of joint pain, but there was no scientific literature available. This species also comes under critically endangered species. AIM OF THE STUDY: The current study aims to evaluate the effect of Iris kashmiriana Baker against nociception and rheumatoid arthritis in experimental rats with In-silico model. MATERIAL AND METHODS: Various extracts of the plant were investigated for their in-vitro antioxidant activity. Acute inflammation and FCA induced in rat model, then acetic acid-induced writhing in mice were used. These anti-rheumatic results were justified by the computational method. RESULTS: The total phenolic and flavonoid concentration of HE extracts were found to be 95.30 ± 2.80 mg/g and 18.18 ± 5.88 mg/g respectively. IC50 and maximum inhibition of HE extracts against DPPH and H2O2 were also effective. Among different doses, 400 mg/kg of HE extracts showed significant (p<0.001) reduction in acute inflammation (16.42 %), in analgesic activity, the HE extract was found statistically (p<0.001) reduced (60.15 %) and in arthritis model, maximum inflammation reduced (25.9%) was found with hydro ethanol extract and statistical significant (p<0.001). and the paw thickness was reduced (27.4 %). Antioxidant activity of HE extract was found to be optimum (37.01%, p<0.001), Superoxide dismutase concentration was found to be optimum (65.12%, p<0.001). In Histopathology, HE 400 mg/kg showed mild inflammation only. The weight of the thymus and spleen were also determined and the HE 400 mg/kg extract inhibited the increase in weight of these organs compared with positive group (28.26 %, and 25.11 %), respectively. CONCLUSION: Among all the different extracts and various doses, the iris kashmiriana Baker hydro-ethanolic (60:40) 400 mg/kg extract showed the best response among all different extracts.

Assessment of Health-Related Quality of Life in Chronic Kidney Disease Patients: A Hospital-Based Cross-Sectional Study.

Background: Health-related quality of life is rapidly becoming recognized as an important indicator of how a disease affects patient lives and for evaluating the quality of care, especially for chronic conditions such as chronic kidney disease (CKD). Objectives: This study is an attempt to assess the quality of life in patients with chronic kidney disease at MMIMSR and also identify characteristics that may be associated with their worsening quality of life. Materials and Methods: This cross-sectional investigation was conducted at the in-patient department (IPD) of the MMIMSR hospital. This study included 105 CKD patients and used a systematic random sampling method for quantitative analysis. This study utilized a 36-item short-form SF-36 (v1.3) questionnaire to assess HRQoL in CKD patients. Descriptive statistics were employed at the baseline. Chi square and ANOVA were used to draw comparisons between two groups or more than two groups, respectively. Logistic regression analysis was utilized to identify the potential QoL determinants. A p value of 0.05 or lower was used to determine statistical significance. Results: Among a total of 105 participants, the mean (±standard deviation) age was found to be 54.53 ± 13.47 years; 48 were male patients, and 57 were female patients. Diabetes Mellitus (61.9%), hypertension (56.2%), chronic glomerulonephritis (7.6%), chronic pyelonephritis (6.7%), and polycystic kidney disease (5.7%) were identified to be the most frequent disorders associated with CKD. The current study also demonstrated that the HRQoL score domains such as symptom problem list, the effect of kidney disease, and the burden of kidney disease decline significantly and progressively as the patient advances into higher stages of CKD (p = 0.005). A similar pattern was observed in work status, sleep, and general health (p < 0.005). Additionally, a statistically significant difference was noted for cognitive function, quality of social interaction, overall health, dialysis staff encouragement, patient satisfaction, social support, physical functioning, role of physical health, pain, emotional well-being, role of emotional health, social functioning, and energy fatigue (p < 0.005). The mean difference for PCS and MCS based on CKD stages was found to be statistically significant (p < 0.005). The PCS and MCS showed a positive correlation with GFR (r = 0.521), and Hb (r = 0.378), GFR (r = 0.836), and Hb (r = 0.488), respectively. Conclusions: The findings of this study demonstrated that a significant decrease in HRQoL was observed among CKD patients, with a progressive deterioration of HRQoL dimensions as the patient advances to end-stage renal disease. This study also revealed that CKD imposes various restrictions on patients' day-to-day lives, particularly in terms of their physical and mental functioning, even in the initial stages of the disease.

Recent Advances in the Prevention and Management of Monkeypox Viral Infection in Humans.

BACKGROUND: There have been several neglected infectious pathogens that have reemerged in the last few decades, including the monkeypox virus, a virus from the orthopoxviral genus that causes monkeypox and is transmitted between animals and humans. The human monkeypox outbreak has spread to several different countries. Because of the outbreak's unusually high case count and lack of connections to endemic nations, there are concerns that the monkeypox transmission pattern may have changed. OBJECTIVE: The current study aimed to provide recent advancements in the prevention and management of the monkeypox virus in humans. METHODOLOGY: We have highlighted recent advancements in the prevention and management of the monkeypox virus in humans in this work. RESULTS: For the treatment and prevention of monkeypox, new medications and vaccinations are being used, and more study is needed to understand the epidemiology, biology, and ecology of the virus in endemic regions and stop future global outbreaks. Vaccines available in the market for the treatment of viruses are JYNEOS and ACAM2000. Some of the antiviral drugs, such as tecovirimat, brincidofovir, cidofovir, trifluridine, and vaccinia immune globulin, are used for the treatment of the monkeypox virus. Some of the vaccines, such as NIOCH-14, Cidofovir, CMX-001, and ST-246, are currently in clinical trials. CONCLUSION: We have, herein, covered features of monkeypox viral biology that are important for risk assessment and getting ready for an outbreak of the monkeypox virus, with a focus on recent advances in knowledge of the virus's host range, evolutionary potential, and potential targets for neutralization.

Electro-conductive chitosan/graphene bio-nanocomposite scaffold for tissue engineering of the central nervous system.

Degenerative central nervous system (CNS) disorders and traumatic brain injuries are common nowadays. These may induce the loss of neuronal cells and delicate connections essential for optimal CNS function. The CNS tissue has restricted regeneration ability, hindering the development of effective therapies. Developing cell and tissue instructive materials may bring up new treatment possibilities. In this study, chitosan-graphene nano platelets (GNPs) composite films were developed to regenerate brain cells. This study evaluates the effects of GNP concentration (0.5, 1 and 2 wt%) and their alignment on mechanical, electrical, surface, protein adsorption and biological properties of the regenerative scaffolds. Incorporating and aligning GNPs into chitosan matrix improved all the physical and biological properties. On reinforced scaffolds, HT22 cell morphology mimics pyramidal brain cells, which are responsible for the brain's highly branched neural network. Additionally, the reinforced scaffolds supported Mesenchymal Stem like Cells growth and were biocompatible in vivo. The alignment of GNPs in the chitosan matrix offered the appropriate physicochemical and biological properties to promote adhesion, proliferation and shape morphogenesis of hippocampal HT22 neuronal cells. Overall, this study delineates the enormous potential offered by the GNP-reinforced scaffolds for regeneration of central nervous system, especially the brain.

Investigation of Pancreatic-beta cells Role in the Biological Process of Ageing.

BACKGROUND: Cellular senescence is associated with the formation and progression of a range of illnesses, including ageing and metabolic disorders such as diabetes mellitus and pancreatic beta cell dysfunction. Ageing and reduced glucose tolerance are interconnected. Often, Diabetes is becoming more common, which is concerning since it raises the risk of a variety of age-dependent disorders such as cardiovascular disease, cancer, Parkinson's disease, stroke, and Alzheimer's disease. OBJECTIVES: The objectives of this study are to find out the most recent research on how ageing affects the functions of pancreatic beta cells, beta cell mass, beta cell senescence, mitochondrial dysfunction, and hormonal imbalance. METHODS: Various research and review manuscripts are gathered from various records such as Google Scholar, PubMed, Mendeley, Scopus, Science Open, the Directory of Open Access Journals, and the Education Resources Information Centre, using different terms like "Diabetes, cellular senescence, beta cells, ageing, insulin, glucose". RESULTS: In this review, we research novel targets in order to discover new strategies to treat diabetes. Abnormal glucose homeostasis and type 2 diabetes mellitus in the elderly may aid in the development of novel medicines to delay or prevent diabetes onset, improve quality of life, and, finally, increase life duration. CONCLUSION: Aging accelerates beta cell senescence by generating premature cell senescence, which is mostly mediated by high glucose levels. Despite higher plasma glucose levels, hepatic gluconeogenesis accelerates and adipose tissue lipolysis rises, resulting in an increase in free fatty acid levels in the blood and worsening insulin resistance throughout the body.

Anti-inflammatory and Anti-arthritic Properties of Mucuna gigantea Plant Extracts: Establishing by Molecular Docking Study.

Background Mucuna giganteais a traditional plant reported in the management of nervous disorders, male infertility, etc., and also exhibits aphrodisiac, anti-oxidant, and anti-diabetic properties. Very few studies are conducted on Mucuna gigantea. It has not been pharmacologically evaluated for rheumatoid arthritis (RA). In RA, the body's natural defence mechanism gets confused and begins to target the healthy tissues in the body, which leads to joint pain, swelling, bone erosion, and joint stiffness. It is a condition that is classified as an auto-immune disorder. Methods In-silico docking depicted that beta-sitosterol is present in Mucuna gigantea out of ligand library prepared based on a literature survey using computational analysis. Inflammation was induced by carrageen and chronic inflammation was induced by Freund's complete adjuvant in the plantar surface of the rats. The petroleum ether, ethanolic and aqueous extracts in three divided doses (75, 150, and 300 mg/kg) were administered orally. Diclofenac sodium (10 mg/kg), prednisolone (5 mg/kg), and methotrexate (0.5 mg/kg) were used as standard. The statistical significance between means was analyzed using one-way ANOVA, followed by Dunnett's multiple range test. The values are expressed as mean ± SD for each group (n=6), and aP<0.0001, bP<0.001, and cP<0.05 were compared with a negative control group. Results Ethanolic and petroleum ether extracts showed a statistically significant aP<0.0001 effect at 3hr with 300mg/kg effect in analgesic activity, whereas aqueous extracts showed statistically significant aP<0.0001 effect at 1.5hr with 150 and 300mg/kg. In the carrageen-induced model, all three extracts at 300 mg/kg showed a statistically significant aP<0.0001 effect from 2- 4hr. In Freund's adjuvant model, all three extracts at all doses showed a statistically significant aP<0.0001 effect. Also, Mucuna gigantea remarkably ameliorated altered WBCs, rheumatoid factor, and positively modified radiographic and histopathological changes. Conclusion Taken together, these results support the traditional use of Mucuna gigantea as a potent anti-inflammatory and anti-arthritic agent that may be proposed for rheumatoid arthritis treatment.

A Concise Review on Natural Products and Their Derivatives for Breast Cancer Treatment.

Cancer is a leading cause of death worldwide. Among other cancers, breast cancer has been found to produce maximum number of cases in 2020. Different factors including geographical, genetic, hormonal, oral contraceptives and modern lifestyle could be responsible for the development of breast cancer and different pathways can be targeted for breast cancer treatment. The various conventional approaches used for the treatment of breast cancer including radiotherapy, chemotherapy, hormone and immunotherapy. But due to the side effects associated with these conventional treatments such as non-selectivity, multidrug resistance and bioavailability, there is a need for the development of better therapeutic agents for breast cancer treatment. Several natural products have been explored for breast cancer treatment. However, many of these natural products suffered from the limitations of poor water solubility and possess toxic side effects. To overcome these limitations, several structural analogs of natural products have been synthesized and possess potent anti-breast cancer effects with less side effects over their precursor molecules. In the present manuscript, we describe the pathogenesis of breast cancer, some potent natural products used in the treatment of breast cancer and their selected structural analogs possessing potent anti-breast cancer effects. Database such as Science direct, Pubmed and Google scholar were searched using keywords 'risk factors', 'screening methods','receptors', and 'natural products and derivatives', Registered clinical trials on selected natural products were also analyzed. Present study concludes that eight selected natural products and their derivatives possess wide potential to exhibit anti-breast cancer effects and could be explored further to develop better chemotherapeutic agents against breast cancer.

The Anti-inflammatory and Anti-arthritis Activity of Garcinia travancorica in a Rat Model: A Proof of Concept with Computational Studies.

Background Rheumatoid arthritis is a progressive disease of human joints characterized by severe pain, stiffness, and tissue damage at the local site. Bone and cartilaginous tissue damage at the synovial joints is initiated by the production of autoantibody induced by inflammatory signaling through cytokines. Objective This study aimed to evaluate the efficacy of Garcinia travancorica against acute and chronic inflammation in a rat model after designing the ligand library and target identification using computational analysis. Methods Acute inflammation was induced by carrageen, and chronic inflammation was induced by Freund's complete adjuvant in the plantar surface of the rats. The petroleum ether, ethanolic, and aqueous extracts in three divided doses (75 mg/kg, 150 mg/kg, and 300 mg/kg) were administered orally. Diclofenac sodium (10 mg/kg), prednisolone (5 mg/kg), and methotrexate (0.5 mg/kg) were used as standard. Various parameters were evaluated, and statistical significance between means was analyzed using one-way ANOVA, followed by Dunnett's multiple range test. Results: Docking-based in-silico screening of the ligand library has revealed the potential of Polyanxanthone-C as an anti-rheumatoid agent, which is supposed to deliver its therapeutic effect by synergistic targeting of interleukin-1, interleukin-6, and tumor necrosis factor receptor type-1. Conclusion: This plant has the potential to be used in the treatment of arthritis-related disorders.

4D Printed Programmable Shape-Morphing Hydrogels as Intraoperative Self-Folding Nerve Conduits for Sutureless Neurorrhaphy.

There are only a few reports of implantable 4D printed biomaterials, most of which exhibit slow deformations rendering them unsuitable for in situ surgical deployment. In this study, a hydrogel system is engineered with defined swelling behaviors, which demonstrated excellent printability in extrusion-based 3D printing and programmed shape deformations post-printing. Shape deformations of the spatially patterned hydrogels with defined infill angles are computationally predicted for a variety of 3D printed structures, which are subsequently validated experimentally. The gels are coated with gelatin-rich nanofibers to augment cell growth. 3D-printed hydrogel sheets with pre-programmed infill patterns rapidly self-rolled into tubes in vivo to serve as nerve-guiding conduits for repairing sciatic nerve defects in a rat model. These 4D-printed hydrogels minimized the complexity of surgeries by tightly clamping the resected ends of the nerves to assist in the healing of peripheral nerve damage, as revealed by histological evaluation and functional assessments for up to 45 days. This work demonstrates that 3D-printed hydrogels can be designed for programmed shape changes by swelling in vivo to yield 4D-printed tissue constructs for the repair of peripheral nerve damage with the potential to be extended in other areas of regenerative medicine.

Circulating MicroRNAs: Diagnostic Value as Biomarkers in the Detection of Non-alcoholic Fatty Liver Diseases and Hepatocellular Carcinoma.

Non-alcoholic fatty liver disease (NAFLD), a metabolic-related disorder, is the most common cause of chronic liver disease which, if left untreated, can progress from simple steatosis to advanced fibrosis and eventually cirrhosis or hepatocellular carcinoma, which is the leading cause of hepatic damage globally. Currently available diagnostic modalities for NAFLD and hepatocellular carcinoma are mostly invasive and of limited precision. A liver biopsy is the most widely used diagnostic tool for hepatic disease. But due to its invasive procedure, it is not practicable for mass screening. Thus, noninvasive biomarkers are needed to diagnose NAFLD and HCC, monitor disease progression, and determine treatment response. Various studies indicated that serum miRNAs could serve as noninvasive biomarkers for both NAFLD and HCC diagnosis because of their association with different histological features of the disease. Although microRNAs are promising and clinically useful biomarkers for hepatic diseases, larger standardization procedures and studies are still required.

Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics.

The liver is a vital organ that plays a crucial role in the physiological operation of the human body. The liver controls the body's detoxification processes as well as the storage and breakdown of red blood cells, plasma protein and hormone production, and red blood cell destruction; therefore, it is vulnerable to their harmful effects, making it more prone to illness. The most frequent complications of chronic liver conditions include cirrhosis, fatty liver, liver fibrosis, hepatitis, and illnesses brought on by alcohol and drugs. Hepatic fibrosis involves the activation of hepatic stellate cells to cause persistent liver damage through the accumulation of cytosolic matrix proteins. The purpose of this review is to educate a concise discussion of the epidemiology of chronic liver disease, the pathogenesis and pathophysiology of liver fibrosis, the symptoms of liver fibrosis progression and regression, the clinical evaluation of liver fibrosis and the research into nanotechnology-based synthetic and herbal treatments for the liver fibrosis is summarized in this article. The herbal remedies summarized in this review article include epigallocathechin-3-gallate, silymarin, oxymatrine, curcumin, tetrandrine, glycyrrhetinic acid, salvianolic acid, plumbagin, Scutellaria baicalnsis Georgi, astragalosides, hawthorn extract, and andrographolides.

SARS CoV-2 Omicron (B. 1.1. 529) Recent Updates and Challenges Worldwide.

The current world is plagued by unpredictability as a result of various COVID-19 variants. The current variants of concern (VOCs) are B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617/B.1.617.2(Delta). WHO classified two variants, delta (B.1.617.2) and omicron (B.1.1.529), as having highly mutable strikes. The WHO predicted that it would be more dangerous than previous variants due to its mutatable capability. The Omicron variant of coronavirus has caused widespread disruption, with countries struggling to manage the massive number of infections. Due to its unique properties, such as protein structure, symptoms, transmission, and epidemiology, this review aims to compare omicron to other variants. Furthermore, we have highlighted vaccines that have been used to combat this pandemic.