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Introduction: Fungal endophytes have mutualistic associations with the plant's host, communicating through genetic and metabolic processes. As a result, they gain the ability to generate therapeutically effective metabolites and their derivatives., Methods: The current study aims to assess antioxidant potential along with the identification of robust metabolites within the crude extract of a potent endophytic fungus Xylaria ellisii isolated from leaf tissues of the Acorus calamus Linn plant.Four endophytic fungi were obtained from leaf tissues of Acorus calamus Linn., and identified morphologically and molecularly as distinct species. Each ethyl acetate extract of the isolated fungi exhibited a unique chemical profile in the HPTLC fingerprint at various wavelengths. The ethyl acetate (EA) extract from the fungal strain ACL-4 (Xylaria ellisii) demonstrated the strongest antioxidant activity among the four fungal endophytes examined, with an EC50 value of 292.64 ± 3.558 μg/mL. Remarkably, fungal endophyte ACL-4 extract exhibited superior antimicrobial activity at the less concentrations compared to ACL-ME extract of leaf crude., Results: The extract of ACL-ME-treated HEK 293T cells exhibited significant toxicity, with an IC50 value of 1481.74 ± 23.772 μg/mL, compared to fungal strain ACL-4-treated HEK 293T cells, which had an IC50 value greater than 2000 μg/mL. Consequently, the crude extract of ACL-4 and ACL-ME along with the standard drug methotrexate exhibited cytotoxic activity against cancer cell line MDA-MB-231 with IC50 concentrations of 146.65 ± 0.394 μg/mL, 528.46 ± 10.912 μg/mL, and 134.11 ± 3.446 μg/mL, respectively. A total of 2,255 compounds were detected through LC-HRMS-based metabolomics in the crude metabolites of Xylaria ellisii, with certain compounds identified in multiple instances. Among this repertoire, 62 robust bioactive compounds were identified through meticulous screening, guided by existing literature. Comparative HPTLC fingerprint analysis, along with antioxidant efficacy assays of ethyl acetate extracts of Xylaria ellisii derived from Acorus calamus leaves and Cassia fistula twigs revealed the host-specific production of bioactive chemicals., Conclusion: The top-scoring Keap1 inhibitors derived from Xylaria ellisii, including Pregabalin (-6.083 Kcal/mol), Ferulic acid (-5.434 Kcal/mol), (R)-Piperidine-2-carboxylic acid (-5.31 Kcal/mol), Genipin (-5.197 Kcal/mol), and Brivaracetam (-5.17 Kcal/mol), respectively were considered as Keap 1 inhibitors, potentially mitigate oxidative stress., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Despite notable progress in treatment modalities, cancer continues to be a prom-inent cause of death globally. Chemotherapy is the main method used to treat cancer, and chemotherapeutic medications are categorized according to how they work. Nevertheless, the issue of multidrug resistance (MDR) is a significant obstacle, impacting almost 90% of cancer patients who receive chemotherapy or innovative targeted medicines. MDR pro-cesses involve the quick metabolism of foreign substances, the accelerated removal of drugs from cells, the stimulation of growth hormones, the enhancement of DNA repair ability, and the influence of genetic variables. Recent studies have mostly concentrated on studying the anticancer effects of dietary phytoconstituents as a possible remedy for overcoming multidrug resistance (MDR). Various bioactive compounds, such as phenolic acids, phe-nylpropanoids, flavonoids, stilbenes, terpenoids, and organo-sulfur compounds, have shown potential in fighting cancer. It is worth mentioning that a number of phenylpro-panoids are now being tested in clinical trials to evaluate their effectiveness in fighting cancer. This review presents a comprehensive summary of the existing knowledge regard-ing dietary phytoconstituents as possible agents for treating cancer, particularly their ability to overcome MDR. This discussion will focus on the mechanisms by which these com-pounds work, as well as the data from both preclinical and clinical studies. Additionally, we have explored the potential future applications of these compounds in the development of cancer therapeutics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Rheumatoid Arthritis is a long-lasted, inflammatory, systemic autoimmune disease that predominantly manifests in people between the ages of 30 and 50 Rheumatoid arthritis is characterized by more than a half-hour of morning stiffness in the affected joints, fever, soreness, swelling, weight loss, tiredness, warm joints, and subcutaneous rheumatoid nodules. Hormonal, genetic, epigenetic, reproductive, and neuroendocrine risk factors, as well as comorbid host variables, are the categories of host-related risk factors associated with the evolution of RA. Additional risk variables that have been linked to RA include food, environmental variables, socioeconomic status, smoking, microbiome, infection agents, and other airborne exposures. The objective of RA therapies is to minimise joint deformity and destruction, minimise discomfort and inflammation in the joints, and maximise joint function.Growing data suggests that the course of Rheumatoid Arthritis is affected by the minimisation of disease activity caused by disease-modifying medications, and that patients may benefit from early antirheumatic medication delivery that modifies illness. While numerous herbs have been explored for their anti-inflammatory properties, it is important to note that not all herbs have been thoroughly researched. This review focuses on seventeen native plant species that have shown either promising or established anti-arthritic effects based on preclinical and clinical studies where available. The review highlights the biochemical and immunological attributes of these herbs, summarizing their therapeutic potential for RA management while also acknowledging the limitations and gaps in current research. This examination provides insights into the potential of these herbal treatments for RA and calls for further research to explore their efficacy and safety in greater depth., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease is an ailment that is linked with the degeneration of the brain cells, and this illness is the main cause of dementia. Metabolic stress affects the activity of the brain in AD via FOXO signaling. The occurrence of AD will significantly surge as the world's population ages, along with lifestyle changes perceived in current decades, indicating a main contributor to such augmented prevalence. Similarly, metabolic disorders of current adulthood, such as obesity, stroke, and diabetes mellitus, have been observed as the risk-causing factors of AD. Environmental influences induce genetic mutations that result in the development of several diseases. Metabolic disorders develop when individuals are exposed to an environment where food is easily accessible and requires minimal energy expenditure. Obesity and diabetes are among the most significant worldwide health concerns. Obesity arises because of an imbalance between the amount of energy consumed and the amount of energy expended, which is caused by both behavioral and physiological factors. Obesity, insulin resistance syndrome, hypertension, and inflammation are factors that contribute to the worldwide risk of developing diabetes mellitus and neurodegenerative diseases. FOXO transcription factors are preserved molecules that play an important part in assorted biological progressions, precisely in aging as well as metabolism. Apoptosis, cell division and differentiation, oxidative stress, metabolism, and lifespan are among the physiological processes that the FOXO proteins are adept at controlling. In this review, we explored the correlation between signaling pathways and the cellular functions of FOXO proteins. We have also summarized the intricate role of FOXO in AD, with a focus on metabolic stress, and discussed the prospect of FOXO as a molecular link between AD and metabolic disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Numerous health hazards are associated with fungal infections, ranging from asymptomatic cases to potentially fatal invasive diseases that are especially dangerous for those with impaired immune systems. The main causes behind these diseases are opportunistic fungi, namely Aspergillus, Candida, and Cryptococcus. Invasive fungal infections (IFIs) require a global response that includes the development of vaccines, standardized protocols for diagnosis, potent antifungal medications, and strategies to stop drug-resistant strains. Improving high-risk group diagnosis and treatment is essential to lowering death rates. This review highlights the substantial health concerns associated with fungal infections, especially in immunocompromised individuals, and identifies Aspergillus, Candida, and Cryptococcus as the main pathogens. It highlights the necessity of international efforts, such as the development of novel diagnostic instruments, imaging methods, and antifungal drugs, to combat these invasive infections. The review also addresses the increasing need for novel treatment approaches in light of the developing resistance to widely used antifungal medications. Furthermore, the significance of secretory proteins in fungal pathogenicity and the potential of combination therapy are investigated. It is also suggested that a multimodal strategy be used to fight these illnesses, given the promise of multivalent vaccinations. Overall, this study emphasizes how critical it is to develop better diagnostic and treatment strategies in order to successfully control and lessen the impact of invasive fungal diseases on the health of the world., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Posaconazole is an antifungal medication used primarily to treat invasive fungal in-fections caused by various organisms, such as Aspergillus, Candida, and certain molds. It be-longs to the class of drugs known as triazole antifungals. Clinical studies have reported posaconazole to be effective in treating various invasive fungal infections, especially in patients who are immunocompromised, such as those with weakened immune systems due to conditions like HIV/AIDS, undergoing chemotherapy, or having received an organ transplant. It has ef-fectively treated invasive candidiasis, aspergillosis, zygomycosis, and other serious fungal in-fections. The effectiveness of the drug varies based on factors, such as the type of infection, the patient's immune status, and the site of infection. This review describes the types of infection, the drug's safety profile, the development of resistance to posaconazole, and strategies to man-age or prevent resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Liquiritin (LIQ), a bioactive flavonoid from Glycyrrhiza species, has shown significant potential in cancer therapy. LIQ exhibits potent inhibitory effects on various cancer cell types, including breast, lung, liver, and colon cancers, while demonstrating low toxicity towards healthy cells. Its anticancer mechanisms include inducing cell cycle arrest, promoting apoptosis, and modulating inflammation-related pathways. Additionally, LIQ impedes angiogenesis and enhances the efficacy of conventional chemotherapies through sensitization and synergistic effects with other natural compounds and targeted therapies. These multifaceted actions highlight LIQ as a promising candidate for further development as an anticancer agent. This abstract provides an overview of LIQ's chemistry, biological effects, and underlying mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The eye is a most delicate organ protected by several complex biological barriers that are static and dynamic. The presence of these ocular barriers retards drug absorption from topically applied dosage forms at the conjunctival sac. The efficient topical delivery of the drug into the globe is more difficult to achieve and there is a need to develop a topical formulation that may reduce the use of injections and increase patient compliance with decreased frequency of administration. In the advancements of research in nanotechnology, nanoemulsions can be used as biocompatible carriers to deliver the drug to the ocular cavity. The lipophilic globules can increase the solubility of hydrophobic cargos which provides increased permeation ability and ocular bioavailability which can sustain drug release and corneal retention. Because of their small size, these formulations do not cause blurring of vision. Nanoemulsions (NEs) over the past decade have been used to treat several ocular diseases in the anterior eye segment. This review summarizes the economic burden, pathology of ocular diseases, formulation considerations for ocular formulations, and recent advances of these NEs as effective carriers for ocular drug delivery highlighting their performance in pre-clinical studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Dengue is a major health burden worldwide, notably in tropical and subtropical countries, with symptoms ranging from asymptomatic infection to severe hemorrhagic or shock syndrome. The clinical and biochemical profile of dengue has been shown in the literature to be expanding as more atypical signs have been added over the past few decades. Most dengue-related symptoms are typically mild to moderate and self-limited. However, intracranial hemorrhage and acute respiratory distress syndrome in severe dengue is an event that has been encountered uncommonly., Case Presentation: A 30-year-old female presented with complaints of fever, headache, cough, and altered sensorium. Later, she was diagnosed with severe dengue fever complicated by dengue hemorrhagic fever, which manifested as subarachnoid and subdural bleeding and acute respiratory distress syndrome. She was managed conservatively with a positive outcome., Conclusion: Atypical manifestation, though rare, should be kept in mind while dealing with severe dengue patients, as early detection based on anticipated risk factors and timely treatment have the potential to save lives., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In the last few decades, it has been largely perceived that the factors affecting the immune system and its varying pathways lead to the pathological progression of inflammation and inflammatory conditions. Chronic inflammation also contributes to common diseases, such as diabetes mellitus, ischemic heart disease, cancer, chronic renal inflammatory disease, non-alcoholic fatty hepat-ic disease, autoimmune diseases and neurodegenerative diseases., Objective: Interestingly, plant sources and secondary metabolites from plants have been increasingly employed in managing acute and chronic inflammatory diseases for centuries. Boswellic acids are pentacyclic triterpenoidal moieties obtained from the oleo gum resin of different Boswellia species., Methods: Detailed data was collected revealing the anti-inflammatory potential of Boswellic acids through various databases., Result: These are pharmacologically active agents that possess promising anti-inflammatory, anti-arthritic, antirheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, and anti-microbial effects., Conclusion: Boswellic acids have been in use since ancient times primarily to treat acute and chronic inflammatory diseases. This review discusses the various mechanisms underlying the inflammatory process and the necessity of such natural products as a medication to treat inflammatory diseases. In addition, a discussion has also been extended to understand the primary targets involved in inflammation. The review further explores the therapeutic potential of boswellic acids in., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

When breast cells divide and multiply out of control, it is called breast cancer. Symptoms include lump formation in the breast, a change in the texture or color of the breast, or a discharge from the nipple. Local or systemic therapy is frequently used to treat breast cancer. Surgical and radiation procedures limited to the affected area are examples of local management. There has been significant worldwide progress in the development of monoclonal antibodies (mAbs) since 1986, when the first therapeutic mAb, Orthoclone OKT3, became commercially available. mAbs can resist the expansion of cancer cells by inducing the destruction of cellular membranes, blocking immune system inhibitors, and preventing the formation of new blood vessels. mAbs can also target growth factor receptors. Understanding the molecular pathways involved in tumor growth and its microenvironment is crucial for developing effective targeted cancer therapeutics. Due to their unique properties, mAbs have a wide range of clinical applications. Antibody-drug conjugates (ADCs) are drugs that improve the therapeutic index by combining an antigen-specific antibody with a payload. This review focuses on the therapeutic applications, mechanistic insights, characteristics, safety aspects, and adverse events of mAbs like trastuzumab, bevacizumab, pertuzumab, ertumaxomab, and atezolizumab in breast cancer treatment. The creation of novel technologies utilizing modified antibodies, such as fragments, conjugates, and multi-specific antibodies, must be a central focus of future studies. This review will help scientists working on developing mAbs to treat cancers more effectively., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Diabetes mellitus is a metabolic disorder characterized by high blood sugar levels. In recent years, T2DM has become a worldwide health issue due to an increase in incidence and prevalence. Diabetic kidney disease (DKD) is one of the devastating consequences of diabetes, especially owing to T2DM and the key clinical manifestation of DKD is weakened renal function and progressive proteinuria. DKD affects approximately 1/3rd of patients with diabetes mellitus, and T2DM is the predominant cause of end-stage kidney disease (ESKD). Several lines of studies have observed the association between vitamin D deficiency and the progression and etiology of type II diabetes mellitus. Emerging experimental evidence has shown that T2DM is associated with various kinds of kidney diseases. Recent evidence has also shown that an alteration in VDR (vitamin D receptor) signaling in podocytes leads to DKD. The present review aims to examine vitamin D metabolism and its correlation with T2DM. Furthermore, we discuss the potential role of vitamin D and VDR in diabetic kidney disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (Aβ), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of Aβ and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of Aβ. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This article covers the triazole-linked nucleic acids where the triazole linkage (TL) replaces the natural phosphate backbone. The replacement is done at either a few selected linkages or all the phosphate linkages. Two triazole linkages, the four-atom TL1 and the six-atom TL2, have been discussed in detail. These triazole-modified oligonucleotides have found a wide range of applications, from therapeutics to synthetic biology. For example, the triazole-linked oligonucleotides have been used in the antisense oligonucleotide (ASO), small interfering RNA (siRNA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology as therapeutic agents. Due to the ease of the synthesis and a wide range of biocompatibility, the triazole linkage TL2 has been used to assemble a functional 300-mer DNA from alkyne- and azide-functionalized 100-mer oligonucleotides as well as an epigenetically modified variant of a 335 base-pair gene from ten short oligonucleotides. These outcomes highlight the potential of triazole-linked nucleic acids and open the doors for other TL designs and artificial backbones to fully exploit the vast potential of artificial nucleic acids in therapeutics, synthetic biology and biotechnology., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Formononetin (FNT), a methoxy isoflavone, is a potential phytoconstituent utilized for refurbishing fractures in bone tissue. Conceding to its involvement in first-pass metabolism followed by glucuronidation, its absorption efficacy is limited. Hence, it belongs to the BCS class II classification., Objective: We designed the present work to enhance FNT oral bioavailability by using Phospholipids (PL) as a promising carrier. Formononetin Phospholipid Complex (FNT-PC) was prepared by the solvent evaporation method and characterized., Methods: FNT-PC was prepared by solvent evaporation method and characterization (FNT-PC) was performed using aqueous/n-octanol solubility and partition coefficient, FTIR, NMR, SEM, and in vivo pharmacokinetic study in female SD rats at 50 mg/kg., Results: Physicochemical properties like aqueous/n-octanol solubility and partition coefficient were enhanced in FNT-PC. The FTIR spectrum confirmed there was no involvement of functional groups in the preparation of FNT-PC. Whereas, the NMR study resulted in the attachment of carbon (C-8) position of FNT by replacing the quaternary amine of PL to form FNT-PC. When scrutinized for its surface morphology, the FNT-PC exhibited the amorphous geometry that remarkably enhanced the dissolution of FNT (p<0.05) from its pure form. This dissolution effect was also affirmed by the per-oral administration of FNT-PC in female Sprague Dawley (SD) rats at 50 mg/kg dose. The pharmacokinetic profile showed the free FNT levels were markedly increased, correspondingly decreasing the conjugated FNT levels in rat plasma., Conclusion: To summarize, FNT-PC could substantially reduce the first-pass metabolism with enhanced free concentration, improving oral bioavailability for therapeutic use., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The popular perennial creeping plant known as Bacopa monnieri (also known as Brahmi) is being utilized in the Indian Ayurvedic medicine practice. It has a variety of bioactive phytoconstituents that have been used therapeutically to treat a number of serious illnesses. Ancient Vedic scholars used this herb because of its pharmacological effects, particularly as a nerve booster and nootropic supporter. However, it is vital to comprehend the active phytochemical components of Bacopa monnieri extract (BME) and their molecular mechanisms in order to better grasp the effect of BME on neurological illnesses and diseases. Understanding its active phytochemical constituents and their molecular processes is essential. Numerous clinical investigations indicated that BME may have neuroprotective benefits, so it is worthwhile to re-evaluate this wellknown plant. Here, we focused on neurological problems as we examined the pharmacological and phytochemical characteristics of BME. For their effective usage in neuroprotection and cognition, many clinical concerns and the synergistic potential of Bacopa extract have been investigated. Alzheimer's disease is a neurological condition caused by the production of reactive oxygen species, which also causes amyloid-beta (Aβ) and tau protein aggregation and increases neuro-inflammation and neurotoxicity. Our review offers a more indepth molecular understanding of the neuroprotective functions of BME, which can also be connected to its therapeutic management of neurological illnesses and cognitive-improving effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease (AD) is a complex neurological disorder that results in cognitive decline. The incidence rates of AD have been increasing, particularly among individuals 60 years of age or older. In June 2021, the US FDA approved aducanumab, the first humanized monoclonal antibody, as a potential therapeutic option for AD. Clinical trials have shown this drug to effectively target the accumulation of Aβ (beta-amyloid) plaques in the brain, and its effectiveness is dependent on the dosage and duration of treatment. Additionally, aducanumab has been associated with improvements in cognitive function. Biogen, the pharmaceutical company responsible for developing and marketing aducanumab, has positioned it as a potential breakthrough for treating cerebral damage in AD. However, the drug has raised concerns due to its high cost, limitations, and potential side effects. AD is a progressive neurological condition that affects memory, cognitive function, and behaviour. It significantly impacts the quality of life of patients and caregivers and strains healthcare systems. Ongoing research focuses on developing disease-modifying therapies that can halt or slow down AD progression. The pathogenesis of AD involves various molecular cascades and signaling pathways. However, the formation of extracellular amyloid plaques is considered a critical mechanism driving the development and progression of the disease. Aducanumab, as a monoclonal antibody, has shown promising results in inhibiting amyloid plaque formation, which is the primary pathological feature of AD. This review explores the signaling pathways and molecular mechanisms through which aducanumab effectively prevents disease pathogenesis in AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Quercetin is a natural flavonoid with various pharmacological actions such as anti-inflammatory, antioxidant, antimicrobial, anticancer, antiviral, antidiabetic, cardioprotective, neuroprotective, and antiviral activities. Looking at these enormous potentials, researchers have explored how they can be used to manage numerous cancers. It's been studied for cancer management due to its anti-angiogenesis, anti-metastatic, and antiproliferative mechanisms. Despite having these proven pharmacological activities, the clinical use of quercetin is limited due to its first-- pass metabolism, poor solubility, and bioavailability. To address these shortcomings, researchers have fabricated various nanocarriers-based formulations to fight cancer. The present review overshadows the pharmacological potential, mechanisms, and application of nanoformulations against different cancers. Teaser: Explore the potential of Quercetin, a natural flavonoid with diverse pharmacological activities, and its nanoformulations in managing various cancers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The current study recognizes the significance of estrogen receptor alpha (ERα) as a member of the nuclear receptor protein family, which holds a central role in the pathophysiology of breast cancer. ERα serves as a valuable prognostic marker, with its established relevance in predicting disease outcomes and treatment responses., Methods: In this study, computational methods are utilized to search for suitable drug-like compounds that demonstrate analogous ligand binding kinetics to ERα., Results: Docking-based simulation screened out the top 5 compounds - ZINC13377936, NCI35753, ZINC35465238, ZINC14726791, and NCI663569 against the targeted protein. Further, their dynamics studies reveal that the compounds ZINC13377936 and NCI35753 exhibit the highest binding stability and affinity., Conclusion: Anticipating the competitive inhibition of ERα protein expression in breast cancer, we envision that both ZINC13377936 and NCI35753 compounds hold substantial promise as potential therapeutic agents. These candidates warrant thorough consideration for rigorous In vitro and In vivo evaluations within the context of clinical trials. The findings from this current investigation carry significant implications for the advancement of future diagnostic and therapeutic approaches for breast cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Amongst different routes of drug delivery systems, ophthalmic drug delivery still requires a careful investigation and strict parameter measurements because the eyes are one of the most sensitive parts of the body and require special attention. The conventional systems for eyes lead to rapid elimination of formulation and hence very small contact time on the ocular epithelium. The current review article covers various types of polymers used in ocular drug delivery along with their applications/ limitations. Polymers are widely used by researchers in prodrug techniques and as a penetration enhancer in ocular delivery. This article covers the role and use of different polymeric systems which makes the final formulation a promising candidate for ophthalmic drug delivery. The researchers are still facing multiple challenges in order to maintain the therapeutic concentration of the drug in the eyes because of its complex structure. There are several barriers that further restrict the intraocular entry of the drug. In order to remove/reduce such challenges, these days various types of polymers are used for ocular delivery in order to develop different drug carrier systems for better efficacy and stability. The polymers used are highly helpful in increasing residence time by increasing the viscosity at the ocular epithelium layer. Such preparations also get easily permeated in ocular cells. The combination of different polymeric properties makes the final formulation stable with prolonged retention, high viscosity, high permeability, and better bioavailability, making the final formulation a promising candidate for ocular drug delivery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Melasma is a skin hyperpigmentary disorder that develops over time. Genetic factors, oxidative stress, female sex hormones, and UV light may all play a role in the disorder's progression., Aims: To compare the levels of oxidative stress and tyrosinase activity in melasma patients with healthy volunteers., Methods: After written consent, 130 patients were enrolled in a case-control study. 65 cases were of melasma disorder, and 65 were served as control. Homogenized skin tissues were taken and used to estimate superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx) (antioxidants), malondialdehyde (MDA) and tyrosine hydroxylase (TH)., Results: Melasma patients had lower basal levels of systemic antioxidants than healthy subjects. Tyrosinase activity was shown to be greater in lesional skin than in non-lesional skin. In controls, there was a good positive relationship between TH and MDA and an excellent negative relationship between GPx and GSH. In melasma patients, there were significant associations between CAT, GPx, SOD and MDA., Conclusions: Increased oxidative stress may affect tyrosinase activity and eumelanin synthesis via the anabolic pathway of melanin synthesis, according to our findings. In conclusion, we discovered a negative relationship between antioxidants and tyrosinase activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neurological disorders are possibly the most prevalent and have been identified to occur among individuals with autism beyond chance. These disorders encompass a diverse range of consequences with neurological causes and have been regarded as a major threat to public mental health. There is no tried-and-true approach for completely protecting the nervous system. Therefore, plant-derived compounds have developed significantly nowadays. Coumestrol (CML) is a potent isoflavone phytoestrogen with a protective effect against neurological dysfunction and has been discovered to be structurally and functionally similar to estrogen. In recent years, more research has been undertaken on phytoestrogens. This research demonstrates the biological complexity of phytoestrogens, which consist of multiple chemical families and function in various ways. This review aimed to explore recent findings on the most significant pharmacological advantages of CML by emphasising neurological benefits. Numerous CML extraction strategies and their pharmacological effects on various neurological disorders, including PD, AD, HD, anxiety, and cognitive impairments, were also documented., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Reflex cardio-vascular and respiratory (CVR) alterations evoked by intraarterial instillation of nociceptive agents are termed vasosensory reflexes. Such responses elicited by optimal doses of inflammatory mediators have been described in our earlier work., Objective: The present study was designed to evaluate the interactions between subthreshold doses of inflammatory mediators on perivascular nociceptive afferents in urethane anesthetized rats., Methods: Healthy male adult rats (Charles-Foster strain) were anesthetized with an intraperitoneal injection of urethane. After anesthesia, the right femoral artery was cannulated. Respiratory movements, blood pressure, and electrocardiogram were recorded. The interactions between subthreshold doses of algogens in the elicitation of vasosensory reflex responses were studied by instillation of bradykinin (1 nM) and histamine (100 μM) into the femoral artery one after the other, in either temporal combination in separate groups of rats. The CVR responses obtained in these groups were then compared with the responses produced by 100 μM histamine and 1 nM bradykinin in saline-pretreated groups, which served as control., Results: Subthreshold doses of histamine elicited transient tachypnoeic, hyperventilatory, hypotensive, and bradycardiac responses, in rats pretreated with subthreshold doses of bradykinin [p < 0.01, two-sided Dunnett's test] but not in saline pretreated groups [p > 0.05, two-sided Dunnett's test]. Similar responses were elicited by bradykinin after histamine pretreatment compared to the saline-pretreated group. Furthermore, CVR responses produced by histamine in the bradykininpretreated group were greater in magnitude as compared to bradykinin-induced responses in the histamine-pretreated group [p < 0.05, two-sided Dunnett's test]., Conclusion: The present study demonstrates that both bradykinin and histamine potentiate one another in the elicitation of vasosensory reflex responses, and bradykinin is a better potentiator than histamine at the level of perivascular nociceptive afferents in producing reflex CVR changes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Quercetin (Qu), a dietary flavonoid, is obtained from many fruits and vegetables such as coriander, broccoli, capers, asparagus, onion, figs, radish leaves, cranberry, walnuts, and citrus fruits. It has proven its role as a nutraceutical owing to numerous pharmacological effects against various diseases in preclinical studies. Despite these facts, Qu and its nanoparticles are less explored in clinical research as a nutraceutical. The present review covers various neuroprotective actions of Qu against various neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. A literature search was conducted to systematically review the various mechanistic pathways through which Qu elicits its neuroprotective actions and the challenges associated with raw Qu that compromise therapeutic efficacy. The nanoformulations developed to enhance Qu's therapeutic efficacy are also covered. Various ongoing/completed clinical trials related to Qu in treating various diseases, including NDs, are also tabulated. Despite these many successes, the exploration of research on Qu-loaded nanoformulations is limited mostly to preclinical studies, probably due to poor drug loading and stability of the formulation, time-consuming steps involved in the formulation, and their poor scale-up capacity. Hence, future efforts are required in this area to reach Qu nanoformulations to the clinical level., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The prevalence of type 2 diabetes mellitus has been increasing worldwide. As the therapeutic options for type 2 diabetes mellitus have evolved over the last 2 decades, national and global guidelines related to type 2 diabetes mellitus pharmacotherapy issued by various organizations have tended to vary in their recommendations. This narrative review aimed to analyze the key recommendations by major global and national guidelines on the initiation of insulin therapy in patients with type 2 diabetes mellitus over the last 20 years. Strategies for insulin therapy for titration and intensification were also assessed. All guidelines recommend initiation of insulin (basal/ premixed/other formulations) when glycemic targets are not achieved despite lifestyle measures and oral antidiabetic drugs. In the recent decade, early initiation of insulin has been recommended when the glycated hemoglobin levels are >10% or blood glucose levels are ≥300 mg/dL (16.7 mmol/L). Initiation is recommended at a dose of 10 units or 0.1-0.2 U/kg. Titration is advised to achieve the optimal dosage, while intensification is recommended when glycemic targets are not achieved despite titrating to an acceptable level. Glucose monitoring at periodic intervals is recommended for adequate glycemic control. The guidelines further suggest that the choice of insulin should be individualized, considering the clinical status of patients with type 2 diabetes mellitus. The physicians as well as patients should be a part of the decisions made regarding the therapeutic choice of regimen, preparation, and delivery device., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Protein kinases modulate the structure and function of proteins by adding phosphate groups to threonine, tyrosine, and serine residues. The phosphorylation process mediated by the kinases regulates several physiological processes, while their overexpression results in the development of chronic diseases, including cancer. Targeting of receptor tyrosine kinase pathways results in the inhibition of angiogenesis and cell proliferation that validates kinases as a key target in the management of aggressive cancers. As such, the identification of protein kinase inhibitors revolutionized the contemporary anticancer therapy by inducing a paradigm shift in the management of disease pathogenesis. Contemporary drug design programs focus on a broad range of kinase targets for the development of novel pharmacophores to manage the overexpression of kinases and their pathophysiology in cancer pathogenesis. In this review, we present the emerging trends in the development of rationally designed molecular inhibitors of kinases over the last five years (2016-2021) and their incipient role in the development of impending anticancer pharmaceuticals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The ongoing pandemic of severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2) has caused an immense public health crisis worldwide. Emerging evidence has suggested that inflammatory response plays a critical role in the pathogenesis and prognosis of the disease. As vitamin D can modulate the immune system, this study has been designed to correlate vitamin D with inflammatory and prognostic markers in COVID-19 patients., Methods: The present study is a retrospective study examining the relationship between vitamin D levels and inflammatory markers in the COVID-19 disease. COVID-19 patients who were investigated for vitamin D, ferritin, D-dimer, C-reactive protein (CRP), and procalcitonin (PCT) level were only included. The patients were divided into hypovitaminosis D, and normal vitamin D. Correlation and logistic regression analyses were carried out to identify the strength and association of hypovitaminosis D with inflammatory markers in COVID-19 disease., Results: The hypovitaminosis D group had significantly higher inflammatory markers compared to the normal vitamin D group. The correlation between hypovitaminosis D and procalcitonin was negative (r = -0.433), with a strong and significant association (p = 0.002). The correlation between hypovitaminosis D, CRP, and ferritin was weak and insignificant. The logistic regression between hypovitaminosis D and procalcitonin established a significant regression equation, leading to a significant linear model., Conclusion: This study concludes that patients with hypovitaminosis D should be treated with vitamin D therapy to reduce the severity of COVID-19 disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

More than 10 million people worldwide have Alzheimer's disease (AD), a degenerative neurological illness and the most prevalent form of dementia. AD's progression in memory loss, cognitive deterioration, and behavioral changes are all symptoms. Amyloid-beta 42 (Aβ42), the hyperphosphorylated forms of microtubule-associated tau protein, and other cellular and systemic alterations are all factors that contribute to cognitive decline in AD. Rather than delivering a possible cure, present therapy strategies focus on reducing disease symptoms. It has long been suggested that various naturally occurring small molecules (plant extract products and microbiological isolates, for example) could be beneficial in preventing or treating disease. Small compounds, such as flavonoids, have attracted much interest recently due to their potential to alleviate cellular stress. Flavonoids have been proven helpful in various ways, including antioxidants, anti-inflammatory agents, and anti-apoptotic agents, but their mechanism remains unknown. The flavonoid therapy of Alzheimer's disease focuses on this review, which includes a comprehensive literature analysis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Curcumin (CRM) is known to possess various therapeutic properties, such as anti-inflammatory and antidiabetic properties, and is, therefore, considered to be an effective therapeutic., Objective: A sensitive method for the estimation of CRM in plasma, as well as fecal matter-based solid self-nano emulsifying drug delivery system (S-SNEDDS), has been reported for the first time., Methods: A bioanalytical method was optimized using Box-Behnken Design having 13 runs and 3 responses. The optimized method was developed using methanol and water (70:30 v/v) with a flow rate of 1 mL/min. Quercetin was used as an internal standard. A specificity test was also performed for the developed CRM solid self-nano emulsifying drug delivery system., Results: The retention time of CRM was found to be 14.18 minutes. The developed method was validated and found to be linear in the range of 50-250 ng/mL with an R 2 of 0.999. Accuracy studies indicated that CRM had a percentage recovery of less than 105% and more than 95%, respectively. Precision studies were carried out for inter, intraday, and inter-analyst precision, and the %RSD was found to be less than 2%. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 3.37 ng/mL and 10.23 ng/mL, respectively. Stability studies for shortterm, long term and freeze-thaw cycles showed a %RSD of less than 2%, indicating the stability of CRM in the plasma matrix. Moreover, the blank fecal microbiota extract slurry did not show any peak at the retention time of CRM in a CRM-loaded solid nanoemulsifying drug delivery system containing fecal microbiota extract indicating its specificity., Conclusion: Hence, the developed method can have clinical implications as it helps estimate CRM in blood samples and also provides a simple and sensitive method for the estimation of plant-based flavonoids along with fecal microbiota extract formulations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Several factors exist that limit the efficacy of lung cancer treatment. These may be tumor-specific delivery of therapeutics, airway geometry, humidity, clearance mechanisms, presence of lung diseases, and therapy against tumor cell resistance. Advancements in drug delivery using nanotechnology based multifunctional nanocarriers, have emerged as a viable method for treating lung cancer with more efficacy and fewer adverse effects. This review does a thorough and critical examination of effective nano-enabled approaches for lung cancer treatment, such as nano-assisted drug delivery systems. In addition, to therapeutic effectiveness, researchers have been working to determine several strategies to produce nanotherapeutics by adjusting the size, drug loading, transport, and retention. Personalized lung tumor therapies using sophisticated nano modalities have the potential to provide great therapeutic advantages based on individual unique genetic markers and disease profiles. Overall, this review provides comprehensive information on newer nanotechnological prospects for improving the management of apoptosis in lung cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The SARS-CoV-2 enters the human airways and comes into contact with the mucous membranes lining the mouth, nose, and eyes. The virus enters the healthy cells and uses cell machinery to make several copies itself. Critically ill patients infected with SARS-CoV-2 may have damaged lungs, air sacs, lining, and walls. Since COVID-19 causes cytokine storm, it damages the alveolar cells of the lungs and fills them with fluid, making it harder to exchange oxygen and carbon dioxide. The SARS-CoV-2 infection causes a range of complications, including mild to critical breathing difficulties. It has been observed that older people suffering from health conditions like cardiomyopathies, nephropathies, metabolic syndrome, and diabetes instigate severe symptoms. Many people who died due to COVID-19 had impaired metabolic health [IMH], characterized by hypertension, dyslipidemia, and hyperglycemia, i.e., diabetes, cardiovascular system, and renal diseases, making their retrieval challenging. Jeopardy stresses for increased mortality from COVID-19 include older age, COPD, ischemic heart disease, diabetes mellitus, and immunosuppression. However, no targeted therapies are available as of now. Almost two-thirds of diagnosed coronavirus patients had cardiovascular diseases and diabetes, out of which 37% were under 60. The NHS audit revealed that with a higher expression of ACE-2 receptors, viral particles could easily bind their protein spikes and get inside the cells, finally causing COVID-19 infection. Hence, people with IMH are more prone to COVID-19 and, ultimately, comorbidities. This review provides enormous information about tissue [lungs, heart, and kidneys] damage, pathophysiological changes, and impaired metabolic health of SARS-CoV-2 infected patients. Moreover, it also designates the possible therapeutic targets of COVID-19 and drugs which can be used against these targets., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Diindolylmethane (DIM), a major acid condensation product of Indole-3- carbinol, is known to inhibit platelet aggregation and thrombosis. The drugs with antiplatelet and antithrombotic activities are used to treat ischemic stroke., Objective: The present study investigated the role of DIM on platelet aggregation inhibitory properties in middle cerebral artery occluded (MCAO) rats., Methods: DIM (12.5, 25, and 50 mg/kg) was orally administered to MCAO rats for 3 days. Platelet aggregation, platelet cyclic adenosine monophosphate (cAMP), reactive oxygen species (ROS), hydrogen peroxide (H2O2), and serum cyclooxygenase (COX-1), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2), and inflammatory markers were estimated. Further brain structural and functional recovery was evaluated by measuring cerebral blood flow, neurological deficits, brain infarction, blood-brain barrier (BBB) leakage, brain water content, and histological abnormalities., Results: DIM significantly ameliorated adenosine diphosphate (ADP), collagen, thrombin, and arachidonic acid-induced platelet aggregation by inhibiting COX-1, TXB2, and PGE2 and elevating cAMP. Further, DIM also alleviated platelet-mediated oxidative stress (ROS and H2O2) and reduced the serum inflammatory markers, tumor necrosis factor-α (TNF-α) and interleukin -6 (IL-6), and increased anti-inflammatory cytokine, IL-10, in MCAO rats., Conclusion: DIM treatment confers neuroprotection in MCAO rats by inhibition of platelet aggregation, platelet-mediated oxidative stress, and inflammation. Correspondingly, DIM improved cerebral blood flow and reduced neurological deficits, brain infarction, BBB leakage, brain water content, and histopathological abnormalities indicating the preservation of brain structural integrity. Thus, the present study provided preclinical evidence of DIM neuroprotection against ischemic stroke., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer is characterized by disrupted molecular variables caused by cells that deviate from regular signal transduction. The uncontrolled segment of such cancerous cells annihilates most of the tissues that contact them. Gene therapy, immunotherapy, and nanotechnology advancements have resulted in novel strategies for anticancer drug delivery. Furthermore, diverse dispersion of nanoparticles in normal stroma cells adversely affects the healthy cells and disrupts the crosstalk of tumour stroma. It can contribute to cancer cell progression inhibition and, conversely, to acquired resistance, enabling cancer cell metastasis and proliferation. The tumour's microenvironment is critical in controlling the dispersion and physiological activities of nano-chemotherapeutics which is one of the targeted drug therapy. As it is one of the methods of treating cancer that involves the use of medications or other substances to specifically target and kill off certain subsets of malignant cells. A targeted therapy may be administered alone or in addition to more conventional methods of care like surgery, chemotherapy, or radiation treatment. The tumour microenvironment, stromatogenesis, barriers and advancement in the drug delivery system across tumour tissue are summarised in this review., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV- 2), is responsible for multiple worldwide lockdowns, an economic crisis, and a substantial increase in hospitalizations for viral pneumonia along with respiratory failure and multiorgan dysfunctions. Recently, the first few vaccines were approved by World Health Organization (WHO) and can eventually save millions of lives. Even though, few drugs are used in emergency like Remdesivir and several other repurposed drugs, still there is no approved drug for COVID-19. The coronaviral encoded proteins involved in host-cell entry, replication, and host-cell invading mechanism are potential therapeutic targets. This perspective review provides the molecular overview of SARS-CoV-2 life cycle for summarizing potential drug targets, structural insights, active site contour map analyses of those selected SARS-CoV-2 protein targets for drug discovery, immunology, and pathogenesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease (AD) is a complex multifactorial neurodegenerative disease characterized by progressive memory loss. The main pathological features of the disease are extracellular deposition of amyloid β (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Understanding factors contributing to AD progression, the number of molecular signatures, and the development of therapeutic agents played a significant role in the discovery of disease-modifying drugs to treat the disease. Bioinformatics has established its significance in many areas of biology. The role of bioinformatics in drug discovery, is emerging significantly and will continue to evolve. In recent years, different bioinformatics methodologies, viz. protein signaling pathway, molecular signature differences between different classes of drugs, interacting profiles of drugs and their potential therapeutic mechanisms, have been applied to identify potential therapeutic targets of AD. Bioinformatics tools were also found to contribute to the discovery of novel drugs, omics-based biomarkers, and drug repurposing for AD. The review aims to explore the applications of various advanced bioinformatics tools in the identification of targets, biomarkers, pathways, and potential therapeutics for the treatment of the disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The lysosomal cysteine protease enzyme, named Cathepsin B, mainly degrades the protein and manages its average turnover in our body. The Cathepsin B active form is mostly present inside the lysosomal part at a cellular level, providing the slightly acidic medium for its activation. Multiple findings on Cathepsin B reveal its involvement in neurons' degeneration and a possible role as a neuronal death mediator in several neurodegenerative diseases. In this review article, we highlight the participation of Cathepsin B in the etiology/progress of AD, along with various other factors. The enzyme is involved in producing neurotoxic Aβ amyloid in the AD brain by acting as the β-secretase enzyme in the regulated secretory pathways responsible for APP processing. Aβ amyloid accumulation and amyloid plaque formation lead to neuronal degeneration, one of the prominent pathological hallmarks of AD. Cathepsin B is also involved in the production of PGlu-Aβ, which is a truncated and highly neurotoxic form of Aβ. Some of the findings also revealed that Cathepsin B specific gene deletion decreases the level of PGlu-Aβ inside the brain of experimental mice. Therefore, neurotoxicity might be considered a new pathological indication of AD due to the involvement of Cathepsin B. It also damages neurons present in the CNS region by producing inflammatory responses and generating mitochondrial ROS. However, Cathepsin B inhibitors, i.e., CA-074, can prevent neuronal death in AD patients. The other natural inhibitors are also equally effective against neuronal damage with higher selectivity. Its synthetic inhibitors are specific for their target; however, they lose their selectivity in the presence of quite a few reducing agents. Therefore, a humanized monoclonal antibody is used as a selective Cathepsin B inhibitor to overcome the problem experienced. The use of Cathepsin B for the treatment of AD and other neurodegenerative diseases could be considered a rational therapeutic target., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Metabiotics have emerged as the safer alternatives to probiotics in last decade. Unlike probiotics that are live microbes, metabiotics are the low molecular weight bioactive metabolites produced by the gut microbiota. While offering a similar profile of health benefits as that of probiotics, metabiotics are free from the risks and uncertain responses associated with administration of live bacteria into the body. Metabiotics have demonstrated substantial effectiveness across the ethnicities, age, gender and nutritional habits in a number of metabolic disorders, including obesity. Obesity is attributed to the offsetting of the energy homeostasis of the body due to a number of genetic, endocrinological, and environmental factors leading to obesity. The obesogenic mechanisms are quite complicated as they result from a complex interplay among a number of factors. Owing to a variety of constituents exerting their action through different pathways, metabiotics offer a pragmatic option for treatment as well as prevention of obesity by addressing heterogeneous aspects of its aetiology. In this review, we categorize various components of metabiotics and discuss their cross-talk with host cells at the molecular level. We also discuss the challenges in understanding these interactions and their potential effects on obesity treatment and prevention strategies. Considering the alarming rise in obesity all over the world, metabiotics offer an attractive non-pharmacological approach to spearhead the strategies being designed to combat the challenges posed by the obesity epidemic., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objective: Psoriasis is an autoimmune skin disease involving cascading release of cytokines activated by the innate and acquired immune system. The increasing prevalence rate of psoriasis demands for more appropriate therapy. The existing chemical moiety is promising for better therapeutic outcome, but the selection of a proper channel for administration has to be reviewed. Hence there is a need to select the most appropriate dosage form and route of administration for improving the curative rate of psoriasis., Results: A total of 108 systematic reviews of research and review articles were conducted to make the manuscript comprehensible. The role of inflammatory mediators in the pathogenesis of the disease is discussed for a better understanding of the selection of pharmacotherapy. The older and newer therapeutic moiety with its mode of administration for psoriasis treatment has been discussed. With a comparative review on topical and oral administration of first-line drugs such as methotrexate (MTX), cyclosporine (CsA), and betamethasone, its benefits-liabilities in the selected routes were accounted for. Emphasis has also been paid on advanced nanocarriers for dermatologic applications., Conclusion: For a better therapeutic outcome, proper selection of drug moiety with its appropriate administration is the major requisite. With the advent of nanotechnology, the development of nanocarrier for dermatologic application has been successfully demonstrated in positioning the systemically administrated drug into topical targeted delivery. In a nutshell, to achieve successful treatment strategies towards psoriasis, there is a need to focus on the development of stable, non-toxic nanocarrier for topical delivery. Inclusion of the existing orally administered drug moiety into nanocarriers for topical delivery is proposed in order to enhance therapeutics payload with reduced side effects which serves as a better treatment approach for relief of the psoriasis condition., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Since its origin in the Wuhan province of China in December 2019, Coronavirus Disease 19 (COVID-19) has spread to most parts of the world and has infected millions of people. However, the significant variability in the mortality rate across the world indicates some underlying factors, especially the immunity factors that may have a potential role in this variability. One such factor that is being discussed and tested is the Bacillus Calmette-Guerin (BCG) vaccine. The available evidence suggests that BCG vaccination provides broad protection against respiratory infections as well as other infections. Therefore, BCG may prove to be a barrier for COVID-19 infection and may offer a ray of hope. In this review, we contrasted BCG vaccination program with COVID-19 mortality and analyzed trained immunity and cross protection against unrelated pathogens due to BCG vaccination. On analyzing the available data, we observed that countries without universal BCG vaccination policy are severely affected, while countries having universal BCG policies are less affected. Based on these data, we propose that the SARS-CoV-2 related qualified immunity, cross protection against unrelated pathogens and COVID-19 impact variations could be partly explained by the different national policies regarding BCG childhood vaccination. The combination of reduced morbidity and mortality may make BCG vaccination a potential new tool in the fight against COVID-19., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Artificial Intelligence revolutionizes the drug development process that can quickly identify potential biologically active compounds from millions of candidate within a short period. The present review is an overview based on some applications of Machine Learning based tools, such as GOLD, Deep PVP, LIB SVM, etc. and the algorithms involved such as support vector machine (SVM), random forest (RF), decision tree and Artificial Neural Network (ANN), etc. at various stages of drug designing and development. These techniques can be employed in SNP discoveries, drug repurposing, ligand-based drug design (LBDD), Ligand-based Virtual Screening (LBVS) and Structure- based Virtual Screening (SBVS), Lead identification, quantitative structure-activity relationship (QSAR) modeling, and ADMET analysis. It is demonstrated that SVM exhibited better performance in indicating that the classification model will have great applications on human intestinal absorption (HIA) predictions. Successful cases have been reported which demonstrate the efficiency of SVM and RF models in identifying JFD00950 as a novel compound targeting against a colon cancer cell line, DLD-1, by inhibition of FEN1 cytotoxic and cleavage activity. Furthermore, a QSAR model was also used to predict flavonoid inhibitory effects on AR activity as a potent treatment for diabetes mellitus (DM), using ANN. Hence, in the era of big data, ML approaches have been evolved as a powerful and efficient way to deal with the huge amounts of generated data from modern drug discovery to model small-molecule drugs, gene biomarkers and identifying the novel drug targets for various diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Worldwide, diabetes ranks among the ten leading causes of mortality. Prevalence of diabetes is growing rapidly in low and middle income countries. It is a progressive disease leading to serious co-morbidities, which results in increased cost of treatment and over-all health system of the country. Pathophysiological alterations in Type 2 Diabetes (T2D) progressed from a simple disturbance in the functioning of the pancreas to triumvirate to ominous octet to egregious eleven to dirty dozen model. Due to complex interplay of multiple hormones in T2D, there may be multifaceted approach in its management. The 'long-term secondary complications' in uncontrolled diabetes may affect almost every organ of the body, and finally may lead to multi-organ dysfunction. Available therapies are inconsistent in maintaining long term glycemic control and their long term use may be associated with adverse effects. There is need for newer drugs, not only for glycemic control but also for prevention or mitigation of secondary microvascular and macrovascular complications. Increased knowledge of the pathophysiology of diabetes has contributed to the development of novel treatments. Several new agents like Glucagon Like Peptide - 1 (GLP-1) agonists, Dipeptidyl Peptidase IV (DPP-4) inhibitors, amylin analogues, Sodium-Glucose transport -2 (SGLT- 2) inhibitors and dual Peroxisome Proliferator-Activated Receptor (PPAR) agonists are available or will be available soon, thus extending the range of therapy for T2D, thereby preventing its long term complications. The article discusses the pathophysiology of diabetes along with its comorbidities, with a focus on existing and novel upcoming antidiabetic drugs which are under investigation. It also dives deep to deliberate upon the novel therapies that are in various stages of development. Adding new options with new mechanisms of action to the treatment armamentarium of diabetes may eventually help improve outcomes and reduce its economic burden., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Huntington's disease (HD) is an autosomal fatal genetic disease in which degeneration of neuronal cells occurs in the central nervous system (CNS). Commonly used therapeutics are cludemonoamine depletors, antipsychotics, antidepressants, and tranquilizers. However, these drugs cannot prevent the psychotic, cognitive, and behavioral dysfunctions associated with HD. In addition to this, their chronic use is limited by their long-term side effects. Herbal drugs offer a plausible alternative to this and have shown substantial therapeutic effects against HD. Moreover, their safety profile is better in terms of side effects. However, due to limited drug solubility and permeability to reach the target site, herbal drugs have not been able to reach the stage of clinical exploration. In recent years, the paradigm of research has been shifted towards the development of herbal drugs based nanoformulations that can enhance their bioavailability and blood-brain barrier permeability. The present review covers the pathophysiology of HD, available biomarkers, phytomedicines explored against HD, ongoing clinical trials on herbal drugs exclusively for treating HD and their nanocarriers, along with their potential neuroprotective effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: A waterborne outbreak of hepatitis E virus occurred in the Jamshedpur city of Jharkhand from March 2018 to October 2018. The aim of the present study is to study the hepatitis E virus outbreak clinically, serologically and etiologically., Methods: Five hundred and eighty-four clinically and biochemically documented cases were screened for the hepatotropic viral markers (HepatitisA, B, C, and E) by the ELISA. Demographic data such as gender, age, clinical diagnosis, location, outcome and time of admission were extracted from the online hospital management system. Water samples from the affected area were tested for HEV RNA detection. Genotyping of HEV virus was carried out by sequencing and phylogenetic analysis., Results: Hepatitis E genotype 1 was confirmed as the major etiological agent in this outbreak due to the faecal contamination of drinking water supply while establishing illegal water connections. Mixed infection of HEV-HAV (5.31%) or HEV-HBV (0.91%) was also detected in the present series of acute viral hepatitis., Conclusion: The study highlights the importance of screening for both enterically transmitted hepatotropic viral markers as well as the parenterally transmitted hepatotropic viral markers during the outbreaks of acute viral hepatitis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The objective of the current research work was to prepare chewable tablets having Acacia catechu extract useful for mouth ulcers using a 3 2 factorial design., Methods: Acacia catechu heartwood extract was prepared using a reported method with some modifications. The extract was characterized using TLC against the catechin marker. Then, drug-excipient interaction studies were carried out. The mixture of drug and excipients was evaluated for pre-compression parameters. With the application of 3 2 factorial design, chewable tablets were prepared using direct compression technique. Prepared tablets were evaluated for post-compression parameters., Results: In vitro drug release study of the developed formulations was investigated both in intact and crushed form of tablets. Based on the in vitro performance, the best formulations were selected (F6, F7 & F8 from intact and F1, F5 & F9 from the crushed group) and subjected to various kinetic models and evaluated for Chewing Difficulty Index (CDI)., Conclusion: The overall results revealed that the formulated chewable tablets complied with the standards and exhibited the satisfactory performance in terms of drug release, chewing difficulty index and other related parameters., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Non-Small Cell Lung Cancer (NSCLC) alone is the leading cause of deaths worldwide. ROS1 is a receptor tyrosine kinase (RTK), eminently recognized as the stereotyped oncogenic driver. These RTKs trigger an array of physiological regulations via cellular signal transduction pathways, which are crucial for cancer development. This attributed ROS1 as an appealing and potential target towards the targeted cancer therapy. The present research aims to propound out an effective contemporary inhibitor for targeting ROS1 with a high affinity., Methods: Molegro Virtual Docker (MVD) provided a flexible docking platform to find out the bestestablished drug as an inhibitor for targeting ROS1. A similarity search was accomplished against the PubChem database to acquire the corresponding inhibitor compounds regarding the Entrectinib (Pub- Chem ID: 25141092). These compounds were docked to procure the high-affinity inhibitor for the target protein via virtual screening. A comparative study between the control molecule (PubChem ID: 25141092)and the virtual screened compound(PubChem ID-25175866) was performed for the relative analysis of their salient features, which involved pharmacophore mapping, ADMET profiling, and BOILED-Egg plot., Results: The virtual screened compound (PubChem ID-25175866) possesses the lowest rerank score (-126.623), and the comparative ADMET analysis also shows that it is a potential and effective inhibitor for ROS1 among the selected inhibitors., Conclusion: The present study provided a scope for the ROS1 inhibitor as significant prevention for nonsmall cell lung cancer (NSCLC). It can be upheld for future studies as a promising support via in vivo studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Diabetic foot ulcer (DFU) is one of the leading complications of type-2 diabetes mellitus. It is associated with neuropathy and peripheral arterial disease of the lower limb in patients with diabetes. There are four stages of wound healing, namely hemostasis phase, inflammatory phase, proliferative phase and maturation phase. In the case of DFU, all these stages are disturbed which lead to delay in healing and consequently to lower limb amputation. Conventional dosage forms like tablets, creams, ointments, gels and capsules have been used for the treatment of diabetic foot ulcer for many years., Introduction: In this review, the global prevalence as well as etiopathogenesis related to diabetic foot ulcer have been discussed. The potential role of various synthetic and herbal drugs, as well as their conventional dosage forms in the effective management of DFU have been discussed in detail., Methods: Structured search of bibliographic databases from previously published peer-reviewed research papers was explored and data has been represented in terms of various approaches that are used for the treatment of DFU., Results: About 148 papers, including both research and review articles, were included in this review to produce a comprehensive as well as a readily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose and mechanism of action., Conclusion: DFU has become one of the most common complications in patients having diabetes for more than ten years. Hence, understanding the root cause and its successful treatment is a big challenge because it depends upon multiple factors such as the judicious selection of drugs as well as proper control of blood sugar level. Most of the drugs that have been used so far either belong to the category of antibiotics, antihyperglycaemic or they have been repositioned. In clinical practice, much focus has been given to dressings that have been used to cover the ulcer. The complete treatment of DFU is still a farfetched dream to be achieved and it is expected that combination therapy of herbal and synthetic drugs with multiple treatment pathways could be able to offer better management of DFU., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in the regulation of cardiorespiratory (CVR) system., Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats., Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 μM) in the absence or presence of antagonists., Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin- induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 μg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly., Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma characterized by the mutation and overexpression of the cyclin D1 protein by the reciprocal chromosomal translocation t(11;14)(q13:q32)., Aim: The present study aims to identify potential inhibition of MMP9, Proteasome, BTK, and TAK1 and determine the most suitable and effective protein target for the MCL., Methodology: Nine known inhibitors for MMP9, 24 for proteasome, 15 for BTK and 14 for TAK1 were screened. SB-3CT (PubChem ID: 9883002), oprozomib (PubChem ID: 25067547), zanubrutinib (PubChem ID: 135565884) and TAK1 inhibitor (PubChem ID: 66760355) were recognized as drugs with high binding capacity with their respective protein receptors. 41, 72, 102 and 3 virtual screened compounds were obtained after the similarity search with compound (PubChem ID:102173753), PubChem compound SCHEMBL15569297 (PubChem ID:72374403), PubChem compound SCHEMBL17075298 (PubChem ID:136970120) and compound CID: 71814473 with best virtual screened compounds., Result: MMP9 inhibitors show commendable affinity and good interaction profile of compound holding PubChem ID:102173753 over the most effective established inhibitor SB-3CT. The pharmacophore study of the best virtual screened compound reveals its high efficacy based on various interactions. The virtual screened compound's better affinity with the target MMP9 protein was deduced using toxicity and integration profile studies., Conclusion: Based on the ADMET profile, the compound (PubChem ID: 102173753) could be a potent drug for MCL treatment. Similar to the established SB-3CT, the compound was non-toxic with LD50 values for both the compounds lying in the same range., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)