Biomarkers of Hepatic Toxicity: An Overview.

Background: Hepatotoxicity is the foremost issue for clinicians and the primary reason for pharmaceutical product recalls. A biomarker is a measurable and quantifiable attribute used to evaluate the efficacy of a treatment or to diagnose a disease. There are various biomarkers which are used for the detection of liver disease and the intent of liver damage. Objective: This review aims to investigate the current state of hepatotoxicity biomarkers and their utility in clinical settings. Using hepatic biomarkers, the presence of liver injury, its severity, prognosis, causative agent, and type of hepatotoxicity can all be determined. Methods: Relevant published articles up to 2022 were systematically retrieved from MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as drug toxicity, hepatotoxicity biomarkers, biochemical parameters, and nonalcoholic fatty liver disease. Results: In clinical trials and everyday practice, biomarkers of drug-induced liver injury are essential for spotting the most severe cases of hepatotoxicity. Hence, developing novel biomarker approaches to enhance hepatotoxicity diagnosis will increase specificity and/or identify the person at risk. Importantly, early clinical studies on patients with liver illness have proved that some biomarkers such as aminotransferase, bilirubin, albumin, and bile acids are even therapeutically beneficial. Conclusions: By assessing the unique signs of liver injury, health care professionals can rapidly and accurately detect liver damage and evaluate its severity. These measures contribute to ensuring prompt and effective medical intervention, hence reducing the risk of long-term liver damage and other major health concerns.

Indian herb Tinospora cordifolia and Tinospora species: Phytochemical and therapeutic application.

Clinical investigations are increasingly focusing on natural materials with medical benefits because, in contrast to medicines, they have extremely few adverse effects. Tinospora species of the Menispermaceae family has many bioactive principles for plant nutraceuticals. A thorough assessment of the existing literature revealed that Indian Tinospora species are an important group of medicinal herbs used for a variety of pharmacological activities. While, Tinospora cordifolia is widely recognized as a significant herb in the Indian System of Medicines (ISM) due to its bioactive components and has been used in the treatment of diabetes, cancer, urinary problems, fever, jaundice, helminthiasis, leprosy, dysentery, skin diseases, and many more. Using the search phrases "phytochemistry," "traditional uses," and "pharmacological evaluation of Indian Tinospora species," appropriate articles were carefully extracted from the MEDLINE/PubMed, Scopus, and WOS databases. Around 180 articles, related to the India Tinospora species, were selected from a pool of 200 papers published between 1991 and 2023. T. cordifolia has received a lot of scientific attention because of its diverse therapeutic characteristics in treating various diseases. Our present study in this review encompasses 1.) Phytochemistry, traditional uses and pharmacological potential of T. cordifolia as well as other Indian Tinospora species. 2.) Safety and toxicity study and available marketed formulation of T. cordifolia for the treatment of various diseases. The chemical constitution and pharmacological characteristics of other Tinospora species must also be investigated, indicating a need for further scientific research.

Quinolone scaffolds as potential drug candidates against infectious microbes: a review.

Prevalence of microbial infections and new rising pathogens are signified as causative agent for variety of serious and lethal health crisis in past years. Despite medical advances, bacterial and fungal infections continue to be a rising problem in the health care system. As more bacteria develop resistance to antibiotics used in therapy, and as more invasive microbial species develop resistance to conventional antimicrobial drugs. Relevant published publications from the last two decades, up to 2024, were systematically retrieved from the MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as quinolones, anti-infective, antibacterial, antimicrobial resistance and patents on quinolone derivatives. With an approach of considerable interest towards novel heterocyclic derivatives as novel anti-infective agents, researchers have explored these as essential tools in vistas of drug design and development. Among heterocycles, quinolones have been regarded extremely essential for the development of novel derivatives, even able to tackle the associated resistance issues. The quinolone scaffold with its bicyclic structure and specific functional groups such as the carbonyl and acidic groups, is indeed considered a valuable functionalities for further lead generation and optimization in drug discovery. Besides, the substitution at N-1, C-3 and C-7 positions also subjected to be having a significant role in anti-infective potential. In this article, we intend to highlight recent quinolone derivatives based on the SAR approach and anti-infective potential such as antibacterial, antifungal, antimalarial, antitubercular, antitrypanosomal and antiviral activities. Moreover, some recent patents granted on quinolone-containing derivatives as anti-infective agents have also been highlighted in tabular form. Due consideration of this, future research in this scaffold is expected to be useful for aspiring scientists to get pharmacologically significant leads.

Understanding the Potential of mRNA as Biomarker to Revolutionize Diagnosis of Colorectal Cancer.

MicroRNA as potential biomarker for early diagnosis, differentiating various stages, interpreting the success of postoperative curative surgery and predicting early relapse of Colorectal cancer.In the realm of medical research, the quest to find effective biomarkers for various diseases has always been a top priority. Colorectal cancer (CRC), one of the leading causes of cancer-related deaths worldwide, is no exception. The emergence of microRNA (mRNA) as a potential biomarker for CRC has sparked immense interest among scientists and clinicians alike. mRNA, a molecule responsible for translating genetic information into functional proteins, presents a promising avenue for early detection and personalized treatment of this deadly disease. By analyzing the specific patterns and levels of mRNA expression in CRC cells, researchers have the ability to identify signatures that can aid in accurate diagnosis, predict patient prognosis, and even guide targeted therapies. This breakthrough in molecular biology not only enhances our understanding of CRC but also holds the potential to revolutionize the field of cancer diagnostics and treatment. In this article, we will delve deeper into the potential of mRNA as a biomarker for CRC, exploring its benefits and challenges in the field of cancer research.

Serum Gamma Glutamyl Transferase: Understanding its Contribution as a Potential Predictor of the Occurrence of Type 2 Diabetes.

INTRODUCTION: The liver and kidneys are the primary locations of the glutathione metabolism enzyme gamma-glutamyl transferase (GGT). The two main factors contributing to an increase are hepatic illnesses and excessive alcohol use. This study set out to test a theory on the predictive importance of the association between GGT and Type 2 diabetes mellitus. (T2DM). METHODS: In order to do this, we combed through PubMed, Google Scholar, Medline, and Science Direct for a wide range of information from previous studies. Attributes were established at the outset and compared to GGT concentration. RESULT: GGT, present in most cells, absorbs glutathione for intracellular antioxidant defences. This study links GGT to hepatic enzymes including HDL, LDL, and triglyceride. LDL, triglycerides, AST, and ALT increased with GGT concentration, but LDL decreased. Because of obesity, GGT production rises with BMI. We found that greater GGT levels were associated with more T2DM after analysing data from multiple sources. CONCLUSION: This literature review concludes that GGT is related to other factors such as BMI, HDL, AST, and triglycerides in the development of diabetes mellitus. Serum GGT was found to be a potential predictor of metabolic syndrome and T2DM.

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.

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.

Novel targets for potential therapeutic use in Diabetes mellitus.

Future targets are a promising prospect to overcome the limitation of conventional and current approaches by providing secure and effective treatment without compromising patient compliance. Diabetes mellitus is a fast-growing problem that has been raised worldwide, from 4% to 6.4% (around 285 million people) in past 30 years. This number may increase to 430 million people in the coming years if there is no better treatment or cure is available. Ageing, obesity and sedentary lifestyle are the key reasons for the worsening of this disease. It always had been a vital challenge, to explore new treatment which could safely and effectively manage diabetes mellitus without compromising patient compliance. Researchers are regularly trying to find out the permanent treatment of this chronic and life threatening disease. In this journey, there are various treatments available in market to manage diabetes mellitus such as insulin, GLP-1 agonist, biguanides, sulphonyl ureas, glinides, thiazolidinediones targeting the receptors which are discovered decade before. PPAR, GIP, FFA1, melatonin are the recent targets that already in the focus for developing new therapies in the treatment of diabetes. Inspite of numerous preclinical studies very few clinical data available due to which this process is in its initial phase. The review also focuses on the receptors like GPCR 119, GPER, Vaspin, Metrnl, Fetuin-A that have role in insulin regulation and have potential to become future targets in treatment for diabetes that may be effective and safer as compared to the conventional and current treatment approaches.

Computational Design of Plant-Based Antistress Agents Targeting Nociceptin Receptor.

Stress is the body's reaction to the challenges it faces, and it produces a multitude of chemical molecules known as stressors as a result of these reactions. It's also a misalignment of the sympathetic and parasympathetic nervous systems causing changes in a variety of physiological reactions and perhaps leading to stress disorders. The reduction in neurotransmitter & neurohormonal hormones is mainly governed by the nociceptin receptor as G-protein coupled receptor and increased the level of reactive oxygen species. Various synthetic medicines that target nociceptin receptors were utilized to reduce the effects of stress but they come up with a variety of side effects. Because of the widespread utilization and renewed interest in medicinal herbal plants considered to be alternative antistress therapy. Our present work is an approach to decipher the molecular nature of novel herbal leads by targeting nociceptin receptor, under which herbal compounds were screened and validated through in-silico methods. Among screened leads, withanolide-B showed stable association in the active site of the nociceptin receptor as an antistress agent with no side effects. Furthermore, the selected lead was also evaluated for stability by molecular dynamic stimulation as well as for pharmacokinetics and toxicity profile. It has been concluded stable conformation of withanolide-B without presence of any major toxic effects. As a result, the in silico molecular docking technique is a highly successful method for selecting a prospective herbal lead molecule with respect to a specific target, and future research can pave the way for further exploration in the drug development field.

Design, Synthesis, Anti-microbial and Molecular Docking Studies of Novel 5-Pyrazyl-2-Sulfanyl-1, 3, 4-Oxadiazole Derivatives.

BACKGROUND: Chemical modification of Oxadiazole may lead to a potent therapeutic agent. A series of novel 5-pyrazyl-2-sulfanyl-1, 3, 4-oxadiazole derivatives (5ag) have been synthesised utilising pyrazinoic acid as a precursor. The new oxadiazole compounds were docked against potential targets and evaluated for antibacterial and antitubercular activity. METHODS: The 5-pyrazyl-2-substituted sulfanyl-1, 3,4-oxadiazole derivatives (5a-g) were synthesized from the crucial intermediate 2-sulfanyl-5-pyrazyl-1, 3,4-oxadiazole (4), which was prepared by treating the 2-pyrazyl hydrazide with CS2 and pyridine. IR, 1HNMR, 13C, MS and elemental analyses were used to confirm the chemical structures. RESULTS: Antimicrobial activity was determined for each synthesized compound. Additionally, compounds were evaluated for antitubercular activity against the Mycobacterium Tuberculosis H37Rv strain. Compounds 5c, 5g, and 5a had a favourable antibacterial profile, while 5c and 5g (MIC = 25 g/ml) demonstrated potential antitubercular activity when compared to the other produced compounds. Molecular docking experiments using V-Life Science MDS 4.6 supplemented the biological data. CONCLUSION: Each compound has been tested for antibacterial and antitubercular action against a variety of microorganism strains and exhibits considerable activity. Additionally, molecular docking analysis confirmed the experimental results by describing improved interaction patterns.

Brassica oleracea Extracts Prevent Hyperglycemia in Type 2 Diabetes Mellitus.

This study investigated the protective effect of extracts from flowers of Brassica oleracea L. var. italica Plenck on type 2 diabetes mellitus and its associated disorders. Three different doses of each extract (petroleum ether, ethanol, and aqueous) were administered orally for 42 days. Biochemical parameters, behavioral studies, and histological studies were measured at different periods. Mortality was found to be nil up to 2,000 mg/kg. Statistically significant (P<0.001) improvement in serum glucose level was observed in the groups receiving 400 mg/kg of petroleum ether, aqueous, or ethanol extracts compared with the negative control group. Insulin level was decreased by aqueous extracts, whereas lipid profiles were improved by aqueous and ethanol extracts. A reduction in transfer latency was observed in treatments of all three extract types. Ethanol extract treatment (400 mg/kg) showed maximum percentage inhibition in a lipid peroxidation assay. Additionally, the aqueous and ethanol extract treatments markedly reduced tumor necrosis factor-α, interleukin-6, and glycosylated hemoglobin levels. Histological results showed that high doses of extracts alleviated the damages induced by type 2 diabetes mellitus in various organs and bones. Based on the results of this study, it can be concluded that B. oleracea has the potential to alleviate type 2 diabetes mellitus.

Medicinal Plants in Cancer Treatment: Contribution of Nuclear Factor- Kappa B (NF-kB) Inhibitors.

Nuclear factor-kappa B (NF-κB) is one of the principal inducible proteins and a predominant transcription factor that is known to control gene expression in mammals. It plays a pivotal role in regulating cell signalling in the body under certain physiological and pathological conditions. In cancer cells, such as colon, breast, pancreatic, ovarian, melanoma, and lymphoma, the NF-κB pathway is active. In cellular proliferation, promoting angiogenesis, invasion, metastasis of tumour cells, and blocking apoptosis, the constitutive activity of NF-κB signalling has been reported. Therefore, immense attention has been given to developing drugs targeting NF-κB signalling pathways to treat many types of tumours. They are a desirable therapeutic target for drugs, and many studies have concentrated on recognizing compounds. They may be able to reverse or standstill the growth and spread of tumours that selectively interfere with this pathway. Recently, numerous substances derived from plants have been evaluated as possible inhibitors of the NF-κB pathway. These include various compounds, such as flavonoids, lignans, diterpenes, sesquiterpenes, polyphenols, etc. A study supported by folk medicine demonstrated that plant-derived compounds could suppress NF-κB signalling. Considering this, the present review revealed the anticancer potential of naturally occurring compounds that inhibit the NF-κB signalling and suppress the growth and spread of cancer.

Recent insight into the biological activities and SAR of quinolone derivatives as multifunctional scaffold.

Quinolones are a type of bicyclic privileged building block with immense therapeutic potential. They are known for their crucial role in modulating numerous diseases conditions. In the present review, quinolone and its derivatives with different pharmacological properties like antibacterial, anticancer, anti-HIV, antitubercular and antimalarial activities are described on the basis of their structure activity relationship studies. Literature is mainly focused on the structural changes responsible for the significant increase in the therapeutic profile of the quinolone scaffold and its derivatives. The substitution pattern in the scaffold responsible for a substantial rise in the potency of specific activity has also been discussed, while emphasizing their potential as lead molecule for the drug discovery and development. Moreover, updates of recent research findings on this scaffold are also discussed.

Styrylquinolines Derivatives: SAR Study and Synthetic Approaches.

In the present-day scenario, heterocyclic derivatives have revealed the primary function of various medicinal agents precious for humanity. Out of a diverse range of heterocycles, Styrylquinolines scaffolds have been proved to play an essential role in a broad range of biological activities, including anti-HIV-1, antimicrobial, anti-inflammatory, anti-Alzheimer activity with antiproliferative effects on tumor cell lines. Due to the immense pharmacological importance, distinct synthetic methods have been executed to attain new drug entities from Styrylquinolines. Various schemes for synthesizing Styrylquinolines derivatives like one-pot, ultrasound-promoted heterogeneous acid-catalysed, microwave-assisted, solvent-free, and green synthesis were discussed in the present review. Some products of Styrylquinolines are in clinical trials, and patents are also granted for the novel synthesis of Styrylquinolines. According to the structure-activity relationship, replacement at the R-7 and R-8 positions is required for various activities. In this review, recent synthetic approaches in the medicinal chemistry of Styrylquinolines and potent Styrylquinolines derivatives based on structural activity relationships (SAR) are outlined. Moreover, their primary methods and modifications are also discussed.

Appropriate Use of Antibiotics for the Management of Respiratory Tract Infections.

Lower Respiratory Tract Infections (LRTIs) and Upper Respiratory Tract Infections (URTIs) cause high morbidity and mortality worldwide. Lower respiratory tract infections are generally more serious than upper infections. Antibiotics are often inappropriately prescribed for patients with RTI. Inappropriate utilization of antibiotics, specifically the broad spectrum in respiratory tract infection, results in resistance to antibiotics. The common use of antibiotics is the prime reason for the spread of drug-resistant bacterial strains, which not only results in expensive treatments but also causes a high rate of morbidity and mortality due to undesired adverse effects of the drug. A literature survey was performed using PubMed, Science Direct, and Web of Science search engines. One hundred forty-five papers were retrieved, and more than 100 were included in this review. This article describes the overview and diagnosis of respiratory tract infections and the plethora of antibiotics that have been used in the management of RTIs.

Exploring Quinolone Scaffold: Unravelling the Chemistry of Anticancer Drug Design.

Globally, cancer is considered as the major leading cause in burdening the patient's health care system globally. The growing threat of drug-resistant cancers renders an urgent need to develop more successful candidates for the anti-cancer therapy. In view of the outstanding pharmacological activities, Quinolone and its derivatives have attracted more attention towards drug designing and biological evaluation in the search for new drug molecules. The inspired researchers attempted efforts in order to discover the quinolone based analogs due to their wide range of biological activities. Due to immense pharmacological importance, distinct synthetic methods have been executed to attain new drug entities from quinolones and all the reported molecules have shown constructive anticancer activities. Some of the synthetic protocols like one pot synthesis, post-Ugi-transformation, catalysed based synthesis, enzyme-based synthesis and nano-catalyst based synthetic procedures are also discussed as recent advancements in the production of quinolone derivatives. In this review, recent synthetic approaches in the medicinal chemistry of quinolones and potent quinolone derivatives on the basis of structural activity relationship are outlined. Moreover, their major methods and modifications are discussed.

Clinical Efficacy of Remdesivir and Favipiravir in the Treatment of COVID-19 Patients: Scenario so far.

The novel SARS-CoV-2 is a new disease that has caused severe destruction to human lives across the globe, including infection, mortality and financial crises, for which, scientific researchers have been directed towards the development of treatment and controlling measures against coronavirus. Currently, there has been no approved drug for the treatment of the disease, but several antiviral drugs have shown therapeutic effects from which, remdesivir and favipiravir are two such drugs. These drugs have shown some therapeutic potential in the treatment of COVID-19 by inhibiting viral enzyme RNA-dependent RNA polymerase. The purpose of this systematic review is to provide an overview of the effectiveness of these two drugs based on the clinical trials reported in current published data.

Urban drinking water security in Gujarat.

Gujarat has made important strides to ensure that most parts of the state become water secure. In 2005, Gujarat was one of the few states that recognized that its urban areas were its 'engines of growth' and made significant investments in urban infrastructure. A state-wide water supply grid was constructed to transfer inter-basin water from perennial surface water sources to water-scarce areas. While these schemes have improved household-level access to municipal water supply, service levels have not improved. In this paper, we argue that along with infrastructure creation, there is a need to focus on monitoring, operation and maintenance of existing system and improving efficiency. We analyze information available from the performance assessment system (PAS) setup by the CEPT University for monitoring of urban services in India. It has annual information of water service delivery in all the urban areas of Gujarat from 2010. We assess urban drinking water supply on three key aspects: equity, service quality and financial sustainability. We also identify a few key intervention areas related to increased accountability, efficiency and equity in delivery of water supply services.

Exploring Azatidinone Moiety: An Insight into its Anti-tubercular Potency.

TB is becoming a worldwide problem and it was declared since 1993 by the World Health Organization (WHO), a global health emergency. The current problem of tuberculosis therapy is the emergence of multi-drug resistant (MDR) strains, caused by the improper use of antibiotics in chemotherapy of TB patients. Azatidinones, a ß-lactam cyclic amide with four atoms in a ring, has been considered as a magic moiety (wonder nucleus) which possesses almost all types of biological activities. This diversity in the biological response profile has attracted the attention of many researchers to explore this skeleton to its multiple potential against several activities. Present article is sincere attempt to review chemistry, method of synthesis of azatidinones and to study azatidinones synthesized in last few years which have shown potent antitubercular activity.