Targeting mitochondria and programmed cell death as potential interventions for metastatic castration-resistant prostate cancer.

Prostate cancer is one of the major causes of morbidity and mortality in men worldwide. Most patients with prostate cancer will turn into end-of-life stage when those tumor cells become metastatic castration-resistant prostate cancer (mCRPC). The mCRPC subsequently developed a resistance to androgen signaling.

Links between oropharyngeal microbiota and IgA nephropathy: A paradigm shift from isolated microbe to microbiome.

Immunoglobulin A nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis globally, yet its pathogenesis remains incompletely understood. While much research has focused on the gut microbiome in the development of the disease, emerging evidence suggests that the oropharyngeal microbiota may also be a potential contributor. Studies have revealed significant alterations in oropharyngeal microbial diversity and specific bacterial taxa in IgAN patients, correlating with disease severity and progression.

Impact of calcineurin inhibitors on gut microbiota: Focus on tacrolimus with evidence from in vivo and clinical studies.

Calcineurin Inhibitors (CNIs), including tacrolimus and cyclosporine A, are the most widely used immunosuppressive drugs in solid organ transplantation. Those drugs play a pivotal role in preventing graft rejection and reducing autoimmunity. However, recent studies indicate that CNIs can disrupt the composition of gut microbiota or result in "gut dysbiosis".

Cyclosorus terminans extract mitigates submandibular gland changes associated with high-fat diet consumption in male rats.

Objectives: To investigate whether the prophylactic effect of Cyclosorus terminans extract mitigates metabolic impairment and submandibular gland changes, as indicated by increased aquaporin5 expression, decreased fibrosis, oxidative stress and inflammation, improved mitochondrial homeostasis/dynamics, and decreased cell death in the submandibular glands of high-fat diet (HFD)-feeding rats.

Methods: Thirty-two male Wistar rats were assigned to either a normal diet (ND) as control rats (n=8) or a HFD (n=24) for 12 weeks. The HFD-treated rats were divided into 3 subgroups to receive either: 1) vehicle (HDV), 2) Cyclosorus terminans at a dose of 100 mg/kg/d (HF100), or 3) Cyclosorus terminans at a dose of 200 mg/kg/d (HF200).

Effects of sodium-glucose cotransporter-2 inhibitor on atrial high-rate episodes in patients with cardiovascular implantable electronic device: a randomized controlled trial.

Prior research has demonstrated an association between sodium-glucose cotransporter 2 (SGLT2) inhibitor and a reduced incidence of atrial fibrillation (AF). Given the established link between mitochondrial dysfunction and AF, this study aimed to explore the impact of SGLT2 inhibitors on AF burden and plausible antiarrhythmic mechanisms in patients with cardiovascular implantable electronic devices (CIEDs). Patients with atrial high-rate episodes (AHREs) detected by CIEDs were randomized to receive either 10 mg of dapagliflozin or a placebo for 3 months.

Exploring alterations of gut/blood microbes in addressing iron overload-induced gut dysbiosis and cognitive impairment in thalassemia patients.

Iron overload causes cognitive impairment in thalassemia patients. The gut-brain axis plays an important role in cognitive function. However, the association between gut/blood microbiome, cognition, and iron burden in thalassemia patients has not been thoroughly investigated.

The Comparative Effects Between Long-Term and Short-Term Treatment of Finasteride on Anxiety-Like and Depression-Like Behaviors in Early Senescent Male Rats.

This study aims to compare the efficacy of 5-alpha-reductase inhibitors (5ARIs) on anxiety and depression between long-term and short-term treatment followed by withdrawal in d-galactose (Dgal)-induced senescent male rats. Thirty-two, 8-week-old, male Wistar rats were divided into two groups: control rats and Dgal-treated rats (150 mg/kg/day; subcutaneously) for 18 weeks. At week 13, Dgal-treated rats were subdivided into three subgroups: (1) vehicle (DgV), (2) long-term treatment with 5ARIs, Finasteride 5 mg/kg/day, per oral for 6 weeks (DgF), (3) short-term treatment with 5ARIs, Finasteride 5 mg/kg/day, per oral for 2 weeks followed by a 4-week withdrawal period (DgW).

Inhibition of 5-alpha reductase attenuates cardiac oxidative damage in obese and aging male rats via the enhancement of antioxidants and the p53 protein suppression.

In aging and metabolic syndrome oxidative stress is a causative factor in the cardiovascular pathology. Upregulation of 5-⍺ reductase is associated with cardiac hypertrophy but how inhibition of 5-⍺ reductase affects cardiometabolic function during oxidative damage under those conditions is unclear. Our hypothesis was that Finasteride (Fin), a 5-⍺ reductase inhibitor, promotes an antioxidant response, leading to an improvement in cardiac function in obese and aging rats.

Atrial pacing improves mitochondrial function in peripheral blood mononuclear cells in patients with cardiac implantable electronic devices.

Mitochondrial dysfunction contributes significantly to the development of atrial fibrillation (AF). Conflicting data regarding the atrial pacing and the risk of AF existed, and the impact of atrial pacing on mitochondrial function remains unknown. Therefore, we sought to examine the association between atrial pacing percentage and mitochondrial function in patients with cardiovascular implantable electronic devices (CIEDs) with atrial pacing capability.

Gestational diabetes mellitus, not obesity, triggers postpartum brain inflammation and premature aging in Sprague-Dawley rats.

Previous studies showed that women with gestational diabetes mellitus (GDM) are susceptible to cognitive dysfunction. We investigated the effects of GDM on brain pathologies and premature brain aging in rats. Seven-week-old female Sprague-Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) after two weeks of acclimatization.

Long-term Treatment with a 5-Alpha-Reductase Inhibitor Alleviates Depression-like Behavior in Obese Male Rats.

Several studies have reported side effects of finasteride (FIN), such as anxiety/depression in young men. Obesity is also positively associated with anxiety/depression symptoms; however, the impacts of long-term FIN treatment and FIN withdrawal in young obese individuals are still elusive. The present study aimed to investigate the effect of long-term treatment and its withdrawal on anxiety/depression and brain pathologies in lean and obese adult male rats.

Mechanistic insights into Lipocalin-2 in ischemic stroke and hemorrhagic brain injury: Integrating animal and clinical studies.

Brain injuries, including strokes and traumatic brain injuries (TBI), are a major global health concern, contributing significantly to both mortality and long-term disability. Recent research has identified lipocalin-2 (LCN2), a glycoprotein secreted by various brain cells, as a key factor in influencing brain injury outcomes. Evidence from animal and clinical studies firmly establishes the pivotal role of LCN2 in driving the inflammatory responses triggered by damage to brain tissue.

Cardiovascular toxicities by calcineurin inhibitors: Cellular mechanisms behind clinical manifestations.

Calcineurin inhibitors (CNI), including cyclosporine A (CsA) and tacrolimus (TAC), are cornerstones of immunosuppressive therapy in solid organ transplant recipients. While extensively recognized for their capacity to induce nephrotoxicity, hypertension, and dyslipidemia, emerging reports suggest potential direct cardiovascular toxicities associated with CNI. Evidence from both in vitro and in vivo studies has demonstrated direct cardiotoxic impact of CNI, manifesting itself as induction of cardiomyocyte apoptosis, enhanced oxidative stress, inflammatory cell infiltration, and cardiac fibrosis.

Potential Roles of Inflammation on Post-Traumatic Osteoarthritis of the Ankle.

Post-traumatic osteoarthritis of the ankle (PTOA) is frequently observed following a debilitating consequence of intra-articular ankle fractures. Numerous risk factors contribute to the pathogenesis of PTOA, including articular incongruity, joint malalignment, and concomitant soft tissue damage. Despite attempts to restore joint anatomy and manage soft tissues to avoid long-term complications after intra-articular ankle fractures, the incidence of PTOA remains markedly elevated.

Chronic mitochondrial dynamic-targeted therapy alleviates left ventricular dysfunction by reducing multiple programmed cell death in post-myocardial infarction rats.

Mitochondrial dysfunction and the activation of multiple programmed cell death (PCD) have been shown to aggravate the severity and mortality associated with the progression of myocardial infarction (MI). Although pharmacological modulation of mitochondrial dynamics, including treatment with the fusion promoter (M1) and the fission inhibitor (Mdivi-1), exerted cardioprotection against several cardiac complications, their roles in the post-MI model have never been investigated. Using a MI rat model instigated by permanent left-anterior descending (LAD) coronary artery occlusion, post-MI rats were randomly assigned to receive one of 4 treatments (n = 10/group): vehicle (DMSO 3%V/V), enalapril (10 mg/kg), Mdivi-1 (1.

Potential biomarkers used for risk estimation of pediatric sepsis-associated organ dysfunction and immune dysregulation.

Pediatric sepsis is a serious issue globally and is a significant cause of illness and death among infants and children. Refractory septic shock and multiple organ dysfunction syndrome are the primary causes of mortality in children with sepsis. However, there is incomplete understanding of mechanistic insight of sepsis associated organ dysfunction.