Genotoxic and cytotoxic effects of aflatoxin on the reproductive system: Focus on cell cycle dynamics and apoptosis in testicular tissue.

Aflatoxins (AFs) are inevitable environmental contaminants that are detrimental to human and animal health. AFs interfere with metabolic processes, metabolizing into different hydroxylated derivatives in the liver, as well as mechanistically induce ROS accumulation, S-phase arrest, DNA damage, and cell apoptosis. Chronic consumption of aflatoxin-contaminated foods can adversely affect the male reproductive system, cause testicular damage, prevent testosterone synthesis, decline sperm quality, and cause infertility. Oxidative stress is the fundamental pathogenesis of aflatoxin-induced reproductive toxicity. The overproduction of reactive oxygen substances can cause testicular failure and disturb the process of spermatogenesis. Mitochondria are susceptible to being impaired by oxidative stress, and its damage is associated with infertility. AFs also disturb the process of spermatogenesis by disrupting the regulation of genes related to the progression of the cell cycle such as cyclins and inducing genes related to apoptosis, thereby weakening fertility and negatively affecting the testicular endocrine potential by suppressing androgen synthesis. Additionally, AFs downregulate ERα expression, potentially negatively impacting spermatogenesis by enhancing the apoptotic mechanism. In this review, we provide new insights into the genotoxic and cytotoxic effects of AFB1 on the male reproductive system with a focus on the cell cycle and apoptosis destruction of testicular tissue.

Updates in the management of atrial fibrillation: Emerging therapies and treatment.

OBJECTIVE: The most common and clinically important cardiac arrhythmia is atrial fibrillation (AF), which has a large negative impact on public health due to higher fatalities, morbidity, and healthcare expenditure rates. This study aims to provide valuable insights into the effectiveness and outcomes of various treatment approaches and interventions for AF. STUDY DESIGN: Systematic review. METHOD: The most pertinent published research (original papers and reviews) in the scientific literature were searched for and critically assessed using the online, internationally indexed databases PubMed, Medline, and Cochrane Reviews. These studies are summarised in this review. Keywords like "Atrial Fibrillation", "emerging therapies", "treatment", "catheter ablation", and "atrial appendage" were used to search the papers. The papers were researched and examined to be relevant to the topic. CONCLUSION: A lot of work has gone into enhancing AF management to deal with this expanding public health concern. Significant developments and advances in the treatment of AF during the past few years have aided clinicians in giving AF patients better care. The most recent treatments for AF include medication, catheter ablation, cryo-balloon ablation, and left atrial appendage closure.

Subclinical leaflet thrombosis and anticoagulation strategy following trans-catheter aortic valve replacement: A systematic review.

Objective: Subclinical leaflet thrombosis (SLT) develops in 15% of patients undergoing trans-catheter aortic valve replacement (TAVR). TAVR is a procedure in which a faulty aortic valve is replaced with a mechanical one. An aortic valve replacement can be done with open-heart surgery; this is called surgical aortic valve replacement (SAVR). A significant problem is defining the best course of treatment for asymptomatic individuals with SLT post-TAVR, including the use of oral anticoagulation (OAC) in it. Study design: Systematic review. Method: The most pertinent published research (original papers and reviews) in the scientific literature were searched for and critically assessed using the online, internationally indexed databases PubMed, Medline, and Cochrane Reviews. Keywords like "Transcatheter valve replacement" and "Subclinical leaflet thrombosis" were used to search the papers. Selected studies were critically assessed for inclusion based on predefined criteria. Results: The review examined the prevalence and characteristics of SLT after TAVR. To note, the incidence of SLT is seen to be higher in TAVR compared SAVR. Dual antiplatelet therapy, which is utilized in antithrombotic regimens post-TAVR, can possibly hasten SLT progression which could result in the impaired mobility of leaflets and the worsening of pressure gradients. Conclusion: The use of dual antiplatelet drugs in routine antithrombotic therapy tends to accelerate initial subclinical leaflet thrombosis after TAVI, which results in a developing restriction of leaflet mobility and an increase in pressure differences.

Neuroprotective effects of flavonoids: endoplasmic reticulum as the target.

The incidence of neurological disorders, particularly age-related neurodegenerative pathologies, exhibits an alarming upward trend, while current pharmacological interventions seldom achieve curative outcomes. Despite their diverse clinical presentations, neurological diseases often share a common pathological thread: the aberrant accumulation of misfolded proteins within the endoplasmic reticulum (ER). This phenomenon, known as ER stress, arises when the cell's intrinsic quality control mechanisms fail to cope with the protein-folding burden. Consequently, misfolded proteins accumulate in the ER lumen, triggering a cascade of cellular stress responses. Recognizing this challenge, researchers have intensified their efforts over the past two decades to explore natural compounds that could potentially slow or even reverse these devastating pathologies. Flavonoids constitute a vast and heterogeneous class of plant polyphenols, with over 10,000 identified from diverse natural sources such as wines, vegetables, medicinal plants, and organic products. Flavonoids are generally divided into six different subclasses: anthocyanidins, flavanones, flavones, flavonols, isoflavones, and flavonols. The diverse family of flavonoids, featuring a common phenolic ring backbone adorned with varying hydroxyl groups and additional modifications, exerts its antioxidant activity by inhibiting the formation of ROS, as evidenced by research. Also, studies suggest that polyphenols such as flavonoids can regulate ER stress through apoptosis and autophagy. By understanding these mechanisms, we can unlock the potential of flavonoids as novel therapeutic agents for neurodegenerative disorders. Therefore, this review critically examines the literature exploring the modulatory effects of flavonoids on various steps of the ER stress in neurological disorders.

Neurological, cardiac, musculoskeletal, and renal manifestations of scleroderma along with insights into its genetics, pathophysiology, diagnostic, and therapeutic updates.

Background: Scleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function. Pathologically, it encompasses the persistent presence of inflammation, abnormal collagen buildup, and restructuring of blood vessels in various organs, resulting in a wide range of clinical symptoms. This review incorporates the most recent scientific literature on scleroderma, with a particular emphasis on its pathophysiology, clinical manifestations, diagnostic approaches, and treatment options. Methodology: A comprehensive investigation was carried out on numerous databases, such as PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar, to collect pertinent studies covering diverse facets of scleroderma research. Results: Scleroderma presents with a range of systemic manifestations, such as interstitial lung disease, gastrointestinal dysmotility, Raynaud's phenomenon, pulmonary arterial hypertension, renal complications, neurological symptoms, and cardiac abnormalities. Serological markers, such as antinuclear antibodies, anti-centromere antibodies, and anti-topoisomerase antibodies, are important for classifying diseases and predicting their outcomes. Discussion: The precise identification of scleroderma is crucial for promptly and correctly implementing effective treatment plans. Treatment approaches aim to improve symptoms, reduce complications, and slow down the progression of the disease. An integrated approach that combines pharmacological agents, including immunosuppressants, endothelin receptor antagonists, and prostanoids, with nonpharmacological interventions such as physical and occupational therapy is essential for maximizing patient care. Conclusion: Through the clarification of existing gaps in knowledge and identification of emerging trends, our goal is to improve the accuracy of diagnosis, enhance the effectiveness of therapeutic interventions, and ultimately enhance the overall quality of life for individuals suffering from scleroderma. Ongoing cooperation and creative research are necessary to advance the field and achieve improved patient outcomes and new therapeutic discoveries.

Inhibitory effects of selected antibiotics on the activities of α-amylase and α-glucosidase: In-vitro, in-vivo and theoretical studies.

Antibiotics are effective drugs that are used to treat infectious diseases either by killing bacteria or slowing down their growth. The well-adapted structural features of antibiotics for the inhibition/activation of enzymes include several available hydrogen bond (H-bond) acceptors and donors, flexible backbone and hydrophobic nature. The substrates of α-amylase and α-glucosidase, known as key absorbing enzymes, have functional groups (OH groups) rembling antibiotics. Given the possibility of developing in diabetics and the significant association between diabetes and infection, the present study was conducted to investigate the influences of tetracycline (TET), kanamycin (KANA), lincomycin (LIN), erythromycin (ERM) and azithromycin (AZM) on α-glucosidase and α-amylase activities with calculating IC50 and Ki values. Also, the efficacy of antibiotics after oral administration was evaluated by analysis of blood glucose concentrations in rats, as well as a molecular docking analysis was explored. α-glucosidase and α-amylase activities were inhibited in a dose dependent fashion by TET with an IC50 of 38.7 ±â€¯1.4 and 47.8 ±â€¯3.2 µM respectively, by KANA with an IC50 of 46.2 ±â€¯1.6 and 65.1 ±â€¯1.6, by LIN with an IC50 of 59.1 ±â€¯2.1 and 51.3 ±â€¯4.1, by ERM with an IC50 of 94.9 ±â€¯4.7 and 65.7 ±â€¯3.8 and by AZM with an IC50 of 69.4 ±â€¯4.4 and 103.6 ±â€¯6.2. Moreover, the Ki values of TET were calculated as 4.4 ±â€¯0.6 and 8.4 ±â€¯0.8 µM for α-glucosidase and α-amylase in a competitive-mode and mixed-mode inhibition. In addition, to communicate with the active site of α-glucosidase and α-amylase respectively, TET presented a binding energy of -9.8 and -8.8 kcal/mol, KANA -7.9 and -7.1, LIN -7.8 and -6.7, ERM -6.8 and -6.4, and AZM -6.4 and -7.5 kcal/mol. In-vivo studies also suggested a decrease in the blood glucose concentration after administering TET compared to the positive controls (P < 0.01). The results obtained from the present research can therefore help the scientific community explore the possible interconnection between the clinical side-effects of antibiotics and their α-glucosidase and α-amylase inhibitory properties, as the target enzymes in hypoglycemia conditions.