This current review provides a thorough examination of the potential of plant-based chemicals as effective male contraceptive treatments by synthesizing results from several preclinical investigations. The established literature highlights the urgent requirement for male contraceptive strategies that are safe, effective, and reversible, considering the drawbacks and difficulties of current options. The need for male contraceptive research and the inherent drawbacks of available solutions are also covered in this review. It clarifies the possible benefits of plant-based contraceptives by emphasizing their natural source, expected safety profile, and low side effect rate. In this review, 49 plants evaluated for male oral contraceptive action are discussed. PubMed, Cochrane library, Embase, ScienceDirect, and Google Scholar databases are used for the literature search. This review explores the complex pathways, including hormone regulation, spermatogenesis suppression, sperm motility interference, and sperm maturation disruption, by which plant-based chemicals may have contraceptive effects. Pre-clinical investigations have examined a wide range of plant-derived substances, including flavonoids, anthraquinones, glycosides, alkaloids, phenolics, diterpenes, triterpenes, tannins, saponins, steroids, and phytosterols, among other phytochemical families. Every phytochemical is thoroughly examined, including its botanical origins, phytoconstituents, native name, and unique effects on male fertility. Results from research conducted on animals are methodically summarised in this study, including information on the effectiveness, dose, delivery methods, and reversibility of contraceptive effects. Furthermore, the discussion includes findings from in vitro research, emphasizing the possible influence on sperm parameters (sperm production, deformation, count, viability, and motility), reproductive hormones (testosterone level), thickness and diameter of seminiferous tubules (ST) as well as spermatocytes and secondary spermatocytes, Sertoli cells (SCs), and Leydig cell (LCs). According to the assessment, male contraceptives made of plants have a lot of potential as a future weapon in the arsenal of contraceptives. Preclinical research has shown the safety, effectiveness, and reversibility of several plant-derived drugs, which offers a solid basis for more investigation and advancement. However, there are still a lot of obstacles to overcome, like standardizing plant extracts, guaranteeing uniform effectiveness, and carrying out thorough safety evaluations. This review emphasizes the significance of undertaking well-designed clinical studies to validate pre-clinical findings, creating standardized formulations for consistent outcomes, and resolving regulatory issues as well as ethical considerations for human use to progress this subject.

BACKGROUND:Monoclonal antibodies (mAbs) are frequently used in the treatment of various types of cancer and autoimmune diseases, but their causal association with Gastrointestinal (GI) disorders is still unclear. The purpose of this study is to evaluate the frequency and nature of GI adverse events (AEs) associated with mAbs reported in the FDA Adverse Event Reporting System (FAERS) database. OBJECTIVES:The study's primary objective was to investigate the GI-AEs linked with mAbs, determine the demographic trends, and evaluate the clinical characteristics (age groups, seriousness, fatality, etc.) from the reported cases. Secondary objectives included using disproportionality signal analysis to find mAb-AEs combinations with significant associations. MATERIALS AND METHODS:Cases involving mAbs from the FAERS database were examined for the period from first authorization until June 30, 2023. The AEs were taken from the "GI Disorders" System Organ Class as standardized Preferred Terms. The characteristics of the cases, such as gender, age, seriousness, and co-suspect drug usage, were examined in detail. Proportional relative risk, IC025, χ2, and Ncomb metrics were used in disproportionality analysis to find the meaningful associations between a particular mAb and GI-AE. RESULTS:A total of 115,346 cases were evaluated, and the most common GI-AEs were caused by rituximab, bevacizumab, and denosumab. Constipation, vomiting, nausea, abdominal pain, and diarrhea were the most commonly reported AEs. 89.17% of cases had serious AEs, and 14.33% had fatal outcomes. Bevacizumab, atezolizumab, and rituximab had the highest death rates. 29 signals were detected by performing the disproportionality analysis for mAbs-GI-AEs combinations having significant values, especially for enterocolitis, ascites, GI perforation, and some other AEs as well, from GI disorders. The highest number of signals was identified by bevacizumab. CONCLUSIONS:This study highlights the strong correlation between mAbs and GI disorders, especially for mAbs such as atezolizumab, rituximab, and bevacizumab. The results emphasise the necessity of increased pharmacovigilance to keep an eye on these AEs and enhance patient safety. Improving patient safety during mAb therapy requires constant safety surveillance and additional research. Further investigation into the mechanisms underlying these relationships could lead to more effective management options for patients undergoing mAb therapy.

The current research work reports the effect of inhibition of LDH (Lactate dehydrogenase) and TGF-β (Transforming growth factor-β) on the metastatic progression of hypoxic mammary gland carcinoma. Using in silico docking studies, Ellagic acid was selected as the inhibitor of LDH, and DITU-1 (a novel compound) as the TGF-β inhibitor. In Vitro anti-cancer potential of both compounds was evaluated in MDA-MB-321 cell lines. DITU-1 and ellagic acid exhibited significant apoptotic potential as evidenced by Anexin V/FIT assay and comet assay. The anti-cancer potential of DITU-1 and ellagic was further validated through in vivo studies. Experimental mammary gland carcinoma was induced in the female SD rats with 7,12-Dimethybenzanthracenes (DMBA-50mg/i.p), and animals were grouped into Normal, toxic control and treatment groups and treated with DITU-1 and ellagic acid combination therapy. A significant increase in tumor size was observed in toxic control animals, which was reduced significantly with combination therapy of DITU-1 and ellagic acid. An increase in angiogenesis was observed through Carmine staining, which was prevented by the combination therapy at low and high doses. Combination therapy also worked well to return to normal, as confirmed by the H-NMR serum metabolic. SEM and Histopathological examination of mammary gland tissue evidenced the protective effect of the combination therapy in retaining the tissue architecture. Immunohistochemistry of HIF-1α, LDH, TGF-β, Vimentin, VEGF and MMP-9 confirmed the anti-metastatic potential of combination therapy at the molecular level. The findings of the current research report that DITU-1 and ellagic acid combination therapy can prevent metastatic progression of hypoxic mammary gland carcinoma.

Road traffic noise (RTN), an emerging environmental stressor, has been linked to adverse gestational outcomes; however, its impact on offspring early reproductive development and potential pharmacological interventions remain insufficiently explored. Oxidative stress and inflammation are considered key mechanisms underlying prenatal stress-induced developmental programming. The current study aims to investigate whether maternal administration of melatonin (MLT) and edaravone (EDV), individually or in combination, can protect against prenatal RTN-induced early testicular development in male offspring and to assess environmental enrichment (EE) as an independent non-pharmacological approach to preserve normal reproductive development. Pregnant Sprague–Dawley rats were randomly assigned to six groups: control, RTN (100 dB(A) SPL), RTN + MLT (5 mg/kg/day, i.p.), RTN + EDV (5 mg/kg/day, i.p.), RTN + MLT + EDV, and EE (independent). Male offspring were evaluated on postnatal day 21 for reproductive organ weights; testicular oxidative stress markers (TBARS and NO₂⁻); antioxidant enzymes (GSH, SOD, and CAT); inflammatory cytokines (TNF-α and IL-6); serum testosterone levels; and testicular histopathological changes. Prenatal RTN exposure was found to be a significant cause of reduced reproductive organ weights, testosterone concentrations, and antioxidant enzyme activities, while increasing lipid peroxidation, nitro-oxidative stress, and pro-inflammatory cytokine levels. The combined gestational administration of MLT and EDV conferred superior restoration of prenatal RTN-induced adverse redox homeostasis, inflammatory status, and testicular structure of offspring compared with either agent alone. However, providing environmental enrichment alone during the gestational period avoided adverse reproductive programming in offspring. The findings identify RTN as a modifiable prenatal environmental risk factor and suggest MLT and EDV as promising pharmacological strategies for mitigating RTN-associated early testicular developmental alterations. Independently, optimized gestational EE was associated with favorable early testicular development. These findings warrant further mechanistic and translational investigation. Prenatal road traffic noise impairs early testicular development in Sprague-Dawley offspring

BACKGROUND:In this study, we aimed to prepare, evaluate, and compare drug-loaded pellets of ketoprofen coated with different triggering mechanisms for colonic delivery. OBJECTIVE:The purpose of this study was to compare Eudragit S100 and Eudragit L100 based pH-dependent, hydroxypropyl cellulose and ethyl cellulose-based time-dependent and high methoxylated pectin and ethyl cellulose-based colonic bacterial enzymatic degradation-dependent coatings over drug-loaded pellets for most efficient colon targeting. METHODS:Any possible drug-polymer interactions were analyzed using Fourier-transform infrared spectroscopy and differential scanning calorimetry. Drug-loaded pellets were prepared using powder layering technology. Different batches of coated pellets were prepared for in vitro evaluation, and optimized batches were selected. These optimized batches were investigated for surface topography by scanning electron microscopy and for colon targeting efficiency by in vivo X-ray roentgenography and gamma scintigraphy studies in white New Zealand rabbits. RESULTS:The drug and polymers were found to be compatible. The prepared coated multi-particulates exhibited favorable micrometric properties. In vitro dissolution studies showed that the polysaccharide pectin high methoxylated and ethyl cellulose-coated optimized batch limited drug release to 16.724 ± 1.124% in the upper gastrointestinal tract and released up to 91.556 ± 3.144% in the colon following zero-order Korsmeyer-peppas super case-II transport (mean dissolution time 36.1779 h). Scanning electron microscopy analysis confirmed the surface characteristics of the pellets before and after dissolution. In vivo studies in New Zealand white rabbits using X-ray roentgenography and gamma scintigraphy demonstrated the optimized batch's gastrointestinal transit and colon targeting efficiency. CONCLUSION:Statistically, the polysaccharide-based formulation showed promising results for targeted drug release in the colon.

Introduction: Mental problems are associated with early neonatal and in utero exposure to maternal stress. With established negative impacts on mental health and cognitive function, road traffic noise (RTN) has emerged as a ubiquitous environmental stressor. In this work, we have examined the effects of maternal exposure to RTN on the development of neurogenesis and spatial memory in the hippocampus (HC) of offspring and investigated possible strategies for mitigating these effects. Method: During the prenatal maturation stage, female Sprague Dawley (SD) rats that were determined to be pregnant were exposed chronically to 100 dB SPL (sound pressure level) RTN for six hours per day. The Morris water maze and elevated plus maze tests were used to evaluate the neurobehavioral performances of the offspring. The oxidative stress and neurogenesis in the HC were evaluated using 2% 2,3,5-triphenyl tetrazolium chloride staining, HC histopathology, and biochemical methods (SOD: superoxide dismutase, GSH: glutathione, CAT: catalase, as well as TBARS: thiobarbituric acid reactive substance, MPO: myeloperoxidase, and AChE: acetylcholinesterase), respectively. Additionally, we looked at the potential therapeutic benefits of melatonin, edaravone, and an enriched environment. Result: The results of our investigation showed that maternal exposure to 100 dB SPL RTN considerably reduced the offspring's spatial memory and caused distress. The biochemical estimation of HC tissue supernatant revealed a considerable increase in MPO, AChE, and TBARS levels and a marked reduction in SOD, CAT, and GSH levels. However, there were notable protective effects against these unfavorable outcomes due to the administration of melatonin and edaravone, as well as from being exposed to an enriched environment. Discussion: In our study, prenatal exposure to 100 dB SPL RTN caused oxidative stress, which caused neurodegeneration, as well as decreased spatial memory and induced anxiety, being consistent with previous findings. In particular, compared to offspring of the 100 dB SPL RTNexposed group, offspring of the maternally treated EDV and MLT combination groups showed superior spatial memory function, reduced anxiety, and increased neurogenesis. Conclusion: The findings of our study have offered promising pathways for public health policies and urban planning concerns, as well as useful insights into the development of tailored therapies to safeguard against the cognitive and neurological repercussions of maternal RTN exposure.

Lactic acidosis is a characteristic feature of solid hypoxic cancerous tumors, those that develop in the breast, colon, and prostate tissue. Even though extreme lactic acidosis is damaging to healthy cells, malignant tumors actually benefit from it in several different ways. Lactic acidosis in TME (TME) imparts resistance to chemotherapy and helps them from immune invasion. Lactic acidosis further benefits the tumor cells by inducing the formation of new blood vessels. Acidic tumour microenvironment (TME) provides very favourable pH conditions for activation of proteolytic enzymes like Matrix metalloproteinase (MMP-2/9), which helps the tumor cells invade into the nearby organs. Because aggressive hypoxic cancer cells have a high chance of metastasising to other organs, it is difficult to manage a tumor at this stage with chemotherapy. Stopping hypoxia-induced Lactate dehydrogenase (LDH) from working can prevent cancers from behaving aggressively. Restraining lactate circulation in the TME by inhibiting LDH and its transporters i.e Monocarboxylate transporters (MCT-1/2) would be a promising therapeutic strategy to prevent metastatic transformation of solid hypoxic tumors. Moreover, nanotechnology can be implicated in various ways to selectively kill the cancer cells. Whereas in some cancers, chemotherapeutic agents fail to activate, pH-sensitive nanoparticles can be designed to target such cancer cells. In the current review, we have highlighted the role and mechanisms of lactic acidosis to transform the benign tumours into more aggressive metastatic tumors. This review also offers fresh perspectives on the variety of LDH and MCT inhibitors currently undergoing clinical trials to act in the acidic TME.

Background Tirzepatide has demonstrated superior efficacy in glycemic control and weight reduction compared to existing GLP-1 receptor agonists. However, its safety profile remains to be fully elucidated in real-world settings. This study examines its safety profile using the EudraVigilance database. Methods We conducted a pharmacovigilance analysis of individual case safety reports (ICSRs) with tirzepatide as the suspected drug using EudraVigilance database. A descriptive analysis was carried out to explore the characteristics of these ICSRs. Disproportionality analysis was performed using reporting odds ratio (ROR) and proportional reporting ratio (PRR) metrics. Results We evaluated 2102 ICSRs where tirzepatide was implicated as the suspected drug. Majority of the ICSRs were reported by healthcare professionals (1299, 61.8%). A total of 5774 AEs associated with tirzepatide were reported with majority being classified as serious (4914, 85.1%). The outcome for most AEs (47.7%, 2754 AEs) was reported as unknown, whereas 30.9% (1784 AEs) were reported as recovered/resolved. AEs associated with the ‘Gastrointestinal Disorders’ SOC (1873, 32.4%) were the most frequently reported, followed by those related to ‘Injury, poisoning and procedural complications’ SOC (641 AEs). Pancreatitis (363) and vomiting (274) emerged as the most commonly reported AEs. The disproportionality analysis indicated a higher reporting frequency of gastrointestinal AEs for tirzepatide (ROR: 1.35, 95% CI: 1.47-1.23; PRR: 1.16, 95% CI: 1.26-1.06) compared to semaglutide, dulaglutide, liraglutide and exenatide. Conclusion This study underscores tirzepatide's safety profile in real-world settings. It highlights the need for ongoing monitoring, especially considering tirzepatide's recent introduction to the market.

The current study was aimed to explore the effect of light and traffic noise pollution exposure on behavioral and neurochemical deficits in adult male Wistar rats. We hypothesized that exposure to these pollutants alone or in combination may cause behavioral deficits in rats. Animals were allocated into different groups and were exposed to either varying light cycles (150 lux-5lux, 14:10 hours) or traffic noise with sound level 100 dBA for 6 h/day or both for 28 days. Concurrently, Curcumin (100 mg/kg; per oral; 28 days) was administered in varying light cycles and noise exposed animal groups to study the preventive effect. After the exposure time, the Morris water maze test, elevated plus maze test, novel object recognition test, locomotor activity test, and forced swimming test were conducted. The neurobehavioral results suggested that only combined exposure of light and noise pollution markedly impaired the learning as well as spatial and reference memory in rats. Furthermore, we found significant anxiety (less no. of open arm entries in EPM) and depressive-like behavior (increased immobility time) in light or/and traffic noise pollution exposed group animals in comparison to normal control groups. Curcumin treatment significantly prevented the behavioral anomalies in combined light and noise exposed rats. Furthermore, our results revealed augmentation of acetylcholinesterase, oxidative stress markers and interleukin (IL)-1β in the hippocampal region of noise and light-exposed groups which were markedly ameliorated by curcumin. In conclusion, our results suggest that curcumin significantly modulates light and noise pollution exposed behavioral and neurochemical anomalies in rats.

BACKGROUND:This study aimed to provide an overview of gastrointestinal (GI) adverse events associated with immune checkpoint inhibitors (ICIs) using two pharmacovigilance databases, EudraVigilance and VigiAccess. RESEARCH DESIGN AND METHODS:Data was collected from the date of ICI's marketing authorization until 30 November 2023. Reporting odds ratio (ROR) was used as a measure of ADR reporting disproportionality for signal detection. RESULTS:Overall, across both databases, EudraVigilance and VigiAccess, a total of 76,606 ADR reports were analyzed. In EudraVigilance, colitis (12,581) and diarrhea (12,108) were the most reported GI adverse events, with similar findings in VigiAccess. Furthermore, in both databases, the most ADR reports were associated with nivolumab and pembrolizumab. Durvalumab (ROR:3.96,95%CI:3.65-4.28), ipilimumab (ROR:1.95,95%CI:1.89-2.01), nivolumab (ROR:1.05,95%CI:1.02-1.07), and atezolizumab (ROR:1.04,95%CI:1.01-1.07) demonstrated higher risks of GI events compared to other ICIs. EudraVigilance analysis identified dysphagia, ascites, hematochezia, and gastroesophageal reflux disease as potential signals associated with ICI therapy. Majority of ADR reports (87.2%) comprised serious GI adverse events, a portion of which was associated with fatal outcomes (14.5%). Atezolizumab (14.9%) and pembrolizumab (11.9%) were linked to a higher incidence of fatal outcomes compared to other ICIs. CONCLUSION:The differential risk profiles of ICIs-associated-GI adverse events underscore the importance of personalized therapy in oncology.

BACKGROUND:Immune checkpoint inhibitors (ICIs) used in immunotherapy have revolutionized cancer management. However, ICI therapy can come with serious neurologic risks. OBJECTIVE:The objective of our study is to analyze the occurrence of neurologic events with ICIs. METHODS:We referred to EudraVigilance (EV) and VigiAccess to evaluate the frequency of individual case safety reports (ICSRs), including neurologic events with ICIs. Data was gathered for a period from the date of ICI's marketing authorization till 30 January 2023. The computational assessment was conducted with the help of reporting odds ratio (ROR) and its 95% confidence interval (CI). RESULTS:Overall, 8181 ICSRs in EV and 15905 ICSRs from VigiAccess were retrieved for neurologic events, with at least one ICI as the suspected drug. The majority of the ICSRs were reported for nivolumab, pembrolizumab, and ipilimumab, whereas frequently reported events were neuropathy peripheral, myasthenia gravis, seizure, Guillain-Barre syndrome, paraesthesia, syncope, encephalopathy, somnolence. Under EV, 92% of ICSRs were reported as serious, 10% included fatal outcomes, and nearly 61% cited patient recovery. Atezolizumab (ROR 1.64, 95% CI 1.75- 1.52), cemiplimab (ROR 1.61, 95% CI 1.98-1.3), and nivolumab (ROR 1.38, 95% CI 1.44-1.31) had a considerable increase in the frequency of ICSR reporting. Cerebrovascular accident, posterior reversible encephalopathy syndrome, tremor, and somnolence were identified as potential signals. CONCLUSION:ICIs were significantly associated with neurologic risks, which cannot be generalized. A considerable increase in ICSR reporting frequency was observed with atezolizumab, cemiplimab, and nivolumab, while avelumab, pembrolizumab, durvalumab, and cemiplimab were linked with four potential signals. These findings suggest the consideration of a revision of the neurologic safety profile of ICIs. Furthermore, the necessity for additional ad-hoc research is emphasized.

Alzheimer's disease (AD), a pathology first described by Alois Alzheimer in 1906, It is a neurodegenerative disorder that is the most common cause of dementia which is characterized by functional and neuronal loss in the brain. It has recently been suggested that mechanisms like chronic neuroinflammation may occur before amyloid-β and tau pathologies in late-onset Alzheimer's disease Neuro-pathological criteria are senile plaques that can potentially get between the neurons, resulting in the accumulation of an inflammatory reaction around deposits of amyloid, fibrillary protein, Aβ, the beta-amyloid precursor protein (APP) and neurofibrillary tangles. Irrespective of the source and mechanisms that lead to the generation of reactive oxygen species, mammalian cells have developed highly regulated inducible defense systems, whose cytoprotective functions are essential in terms of cell survival. Some experts have proposed that Inflammation clears in pathologically vulnerable regions of AD and several inflammatory factors influencing AD development, i.e., environmental and/or genetic factors have been described. Obesity and systemic inflammation may also interfere with immunological processes which promote disease progression. This study suggest that assess the association between neuroinflammation and a variety of clinical studies and treatment strategies for Alzheimer's disease and some natural compounds may also provide a new therapeutic line of approach to this brain neurodegenerative disorder.

Background: Monoclonal antibodies (mAbs), are pivotal in treating various diseases including cancers and autoimmune disorders. Despite their therapeutic benefits, mAbs therapy has been associated with neurological toxicity. Objectives: This study aimed to assess the incidence of neuronal toxicity associated with mAbs, utilizing data from the FDA Adverse Event Reporting System (FAERS) safety database. The study also sought to delineate the medical characteristics of the reported cases. Methods: A comprehensive analysis of neurological adverse events reported in the FAERS database was conducted, employing computational methodologies such as proportional relative risk (PRR), information component (IC025), and Chi-Square (χ2). Individual case safety reports (ICSRs) pertaining to neurological disorders linked to mAbs from the date of first global marketing authorization until June 30, 2023, were meticulously examined. Results: The FAERS safety database contains 79,022 Individual Case Safety Reports (ICSRs) linking monoclonal antibodies (mAbs) to Nervous system disorders. Rituximab, Bevacizumab, Denosumab, Nivolumab, and Trastuzumab were frequently cited. Reported adverse events include headache, peripheral neuropathy, dizziness, and cerebrovascular accident. Most ICSRs (85.81%) were serious, mainly affecting females (57.04%) with a 14.09% fatality rate. Panitumumab, Atezolizumab, Bevacizumab, and Trastuzumab showed strong drug-event associations. Signal Disproportionate Reporting (SDR) analysis flagged myasthenia gravis, peripheral neuropathy, and neurotoxicity across multiple mAbs, suggesting potential signals. Conclusions: Interdisciplinary collaboration between oncologists and neurologists is crucial for safe mAb use. Our study enhances understanding of mAb neurological safety. Disproportionality signal analysis provides valuable evidence for risk mitigation.

Background and objectives In critically ill patients, acute kidney injury (AKI) influences mortality and morbidity. Few studies have looked at mortality and the frequency of AKI following successful heart and thoracic operations. The current study investigates the association between AKI and mortality rates among patients undergoing post-cardiac surgery care within the Cardiology & Cardio Vascular Thoracic Surgery (CVTS) Intensive Care Unit (ICU). Methodology In this prospective research, 124 patients who underwent successful cardiovascular and thoracic procedures between June 2022 and June 2023 were admitted to the CVTS ICU. To determine mortality, we contrasted the two scoring methods, Kidney Disease-Improving Global Outcomes (KDIGO) and Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE). Results Based on the KDIGO criteria, AKI was identified in 37.90% (n = 47) of the patients, and it was identified in 15.32% (n = 19) of the patients utilizing RIFLE. Notably, patients diagnosed with AKI using either the RIFLE criteria or KDIGO criteria exhibited considerably higher mortality rates (p< 0.001). Receiver operating characteristic (ROC) analysis demonstrated the effectiveness of both scoring systems in identifying mortality (area under the ROC curve for RIFLE = 0.224 and KDIGO = 0.150). Conclusion Post-cardiac surgery, AKI escalates both mortality and morbidity rates. Despite KDIGO detecting more severe renal injury and mortality, both scoring systems exhibit comparable sensitivity and specificity in predicting death among patients undergoing various cardiovascular and thoracic procedures.

INTRODUCTION Doxorubicin (DOX) is a widely used anticancer drug known for its significant cardiotoxic and nephrotoxic effects. Seeking remedies to mitigate these adverse effects is crucial. This study investigates the potential of Emblica officinalis (Amla) extract, a prominent component in Chinese and Indian traditional medicine systems, in alleviating DOX-induced cardiotoxicity and nephrotoxicity. METHODS DOX (20 mg/kg i.p., once) was given to rats to cause acute cardiotoxicity and nephrotoxicity. Rats received 16 similar and cumulative doses of DOX (1.25 mg/kg, i.p.) on alternate days for chronic cardiotoxicity and nephrotoxicity. Biochemical and histological evaluations were done to confirm the onset of cardiotoxicity and nephrotoxicity. RESULTS The cardioprotective and nephroprotective effects of Amla extract (AE) (150 mg/kg p.o. and 300 mg/kg p.o) were evaluated in comparison to Vitamin E (25 mg/kg p.o.). The treatment with AE (300 mg/kg/day, p.o.) considerably prevented DOX-induced cardiotoxicity, nephrotoxicity, and oxidative stress by positively altering the integrity of glomeruli, restoring the tissue GSH and decreasing serum TBARS. AE (300 mg/kg) was found to be more cardioprotective and nephroprotective than Vitamin E (25 mg/kg p.o.). DISCUSSION It may be concluded that the induction of cardiotoxicity and nephrotoxicity in rats may be due to DOX-induced oxidative stress, and chronic treatment with AE (300 mg/kg) is an effective way to alleviate the cardiotoxic and nephrotoxic adverse effects of DOX in rats. Moreover, given Amla's historical and contemporary significance in Chinese and Indian traditional medicine systems, its potential therapeutic role merits further exploration in clinical settings.

Background: A substantial amount of evidence indicates that long-term arsenic exposure leads to various types of pathological complications, especially cognitive dysfunction. Objective: The present study was designed to assess the neuroprotective potential of edaravone (a potent free radical scavenger) against arsenic-induced neurotoxicity in Wistar rats. Methods: Adult male Wistar rats were randomly divided into five groups. Arsenic (20 mg/kg/day; p.o.) and Edaravone (5 and 10 mg/kg/day; i.p.) were administered in different experimental groups for 28 days. Results: The results of various behavioral test paradigms revealed that arsenic caused significant learning and memory deficits, along with anxiety-like behavior. In biochemical analysis, we found marked elevations of oxidative-nitrosative stress (indicated by augmentation of lipid peroxidation and nitrite) and a reduction of glutathione levels in the hippocampus and frontal cortex region of arsenic-treated rats. Moreover, arsenic administration caused mitochondrial complexes impairment and reduction of acetylcholinesterase level. On the other hand, chronic treatment with edaravone (10 mg/kg) significantly ameliorated the arsenic-induced behavioral deficits and neurochemical anomalies. Conclusion: This study suggests that edaravone confers neuroprotection against arsenic-induced memory impairment and anxiety-like behavior, which may be attributed to the inhibition of oxidative-nitrosative stress and amelioration of cholinergic and mitochondrial functions.

BACKGROUND:Targeted therapy with type II kinase inhibitors (KIs) is one of the preferred choices in cancer treatment. However, type II KI therapy can be associated to serious cardiac risks.OBJECTIVES:This study aimed to assess the occurrence of cardiac events reported with type II KIs in Eudravigilance (EV) and VigiAccess databases.METHODS:To evaluate reporting frequency of individual case safety reports (ICSRs) related to cardiac events, we referred EV and VigiAccess databases. The data was retrieved for the period from date of marketing authorization of respective type II KI till 30 July 2022. Computational analysis was conducted with data from EV and VigiAccess using reporting odds ratio (ROR) along with its 95% confidence interval (CI) under Microsoft excel.RESULTS:In total, 14429 ICSRs in EV and 11522 ICSRs from VigiAccess were retrieved concerning cardiac events with at least one type II KI as the suspected drug. In both databases, most of the ICSRs were reported for Imatinib, Nilotinib, and Sunitinib, while most reported cardiac events were myocardial infarction/acute myocardial infarction, cardiac failure/congestive heart failure and atrial fibrillation. As per EV, 98.8% ICSRs with cardiac ADRs were assessed as serious and of which, 17.4% ICSRs were associated with fatal outcomes and approximately 47% included patient's recovery as a favorable outcome. Nilotinib (ROR 2.87, 95% CI 3.01-2.74) and Nintedanib (ROR 2.17, 95% CI 2.3-2.04) were associated with a significant increase in reporting frequency of ICSRs related to cardiac events.CONCLUSIONS:Type II KI related cardiac events were serious and associated with unfavorable outcomes. A significant increase in ICSRs reporting frequency was observed with Nilotinib and Nintedanib. These results insist for a consideration of revision of cardiac safety profile of Nilotinib and Nintedanib, specifically for risks of myocardial infarction and atrial fibrillation. Additionally, the need for other ad-hoc studies is indicated.

Broad-spectrum antibiotics such as tetracycline and chloramphenicol bind to the elongating ribosome and prevent the transfer of the ternary complex aminoacylated-tRNA and EF-Tu, GTP to the A-site. Tetracycline's major binding site is in the 30S subunit's helix 34 (h34) of the 16S rRNA, which overlaps the anticodon stem loop of the A-site tRNA. Tetracycline and Chloramphenicol has been widely used in both animals and people for the past 60 years, resulting in a surge in tetracycline resistance. Tetracycline resistance is caused through the acquisition of novel genes that code for energy-dependent tetracycline efflux, a protein that shields bacterial ribosomes from tetracycline action or enzymatic inactivation, and a protein with unclear mode of action. Chloramphenicol resistance is caused by chloramphenicol acetyltransferases, which render chloramphenicol inert. There are two varieties of CAT enzymes, each of which is genetically distinct. Chloramphenicol might possibly be attributed to chloramphenicol efflux via membrane-associated transporters. Both the genes coding for CATs and particular exporters are frequently connected with mobile elements such as plasmids, transposons, or gene cassettes and can be transmitted between bacteria of different species and genera by conjugation, mobilization, transduction, or transformation. Chloramphenicol-exporting chromosomal multidrug transporters have also been discovered. Chloramphenicol can also be caused by mutations that diminish outer membrane protein production, alterations in the 23S rRNA, 3-O-phosphotransferase inactivation of chloramphenicol, or target site modification by a 23S rRNA methylase.

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME.

Injectable hydrogels have the potential to revolutionize therapeutics.