Advancing mitochondrial therapeutics: Synthesis and pharmacological evaluation of pyrazole-based inhibitors targeting the mitochondrial pyruvate carrier.

Inhibition of mitochondrial pyruvate transport via the mitochondrial pyruvate carrier (MPC) has shown beneficial effects in treating metabolic diseases, certain cancers, various forms of neurodegeneration, and hair loss. These benefits arise either from the direct inhibition of mitochondrial pyruvate metabolism or from the metabolic rewiring when pyruvate entry is inhibited. However, current MPC inhibitors are either nonspecific or possess poor pharmacokinetic properties.

Effect of meditation, muscle relaxation exercises, dietary and lifestyle modification on depression, anxiety, stress and self-esteem among women undergoing infertility treatment: A randomized controlled trial: Pilot protocol.

Background: Infertility is not only a reproductive health problem; it's also emotionally painful. Currently, treatments for infertility are receiving more attention, but emotional support is equally important. The aim of this study was to assess the effect of meditation, exercises, dietary, and life-style modifications on depression, anxiety, stress, and self-esteem among infertile women.

Tailoring FXR Modulators for Intestinal Specificity: Recent Progress and Insights.

While FXR has shown promise in regulating bile acid synthesis and maintaining glucose and lipid homeostasis, undesired side effects have been observed in clinical trials. To address this issue, the development of intestinally restricted FXR modulators has gained attention as a new avenue for drug design with the potential for safer systematic effects. Our review examines all currently known intestinally restricted FXR ligands and provides insights into the steps taken to enhance intestinal selectivity.

Impact of HER2-Low Status in Metastatic Gastric Cancer: A Real-World Retrospective Cohort Study.

Introduction: Information regarding HER2-low tumors in metastatic gastric cancer is sparse. Our aim here was to determine the frequency of low HER2 expression in metastatic gastric cancer and to compare the clinicopathological characteristics, survival, and treatment response of HER2-low patients with HER2-zero patients.

Methods: The clinicopathological features, treatment responses, and survival of HER2-low tumors and HER2-zero tumors were compared.

2,5-Diketopiperazines (DKPs): Promising Scaffolds for Anticancer Agents.

2,5-Diketopiperazine (2,5-DKP) derivatives represent a family of secondary metabolites widely produced by bacteria, fungi, plants, animals, and marine organisms. Many natural products with DKP scaffolds exhibited various pharmacological activities such as antiviral, antifungal, antibacterial, and antitumor. 2,5-DKPs are recognized as privileged structures in medicinal chemistry, and compounds that incorporate the 2,5-DKP scaffold have been extensively investigated for their anticancer properties.

Synthesis of 3-Aminoquinazolinones via a SnCl-Mediated ANRORC-like Reductive Rearrangement of 1,3,4-Oxadiazoles.

Herein, we developed a new SnCl-mediated ANRORC (addition of nucleophile, ring-opening, and ring-closure)-like rearrangement for the synthesis of 3-amino-2-substituted-quinazolin-4(3)-one from 2-(2-nitrophenyl)-5-substituted-1,3,4-oxadiazole. The new method is solvent-dependent and features the use of a green solvent system (i.e.

Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney.

A gradual decline in renal function occurs even in healthy aging individuals. In addition to aging, per se, concurrent metabolic syndrome and hypertension, which are common in the aging population, can induce mitochondrial dysfunction and inflammation, which collectively contribute to age-related kidney dysfunction and disease. This study examined the role of the nuclear hormone receptors, the estrogen-related receptors (ERRs), in regulation of age-related mitochondrial dysfunction and inflammation.

Identification of new 4-(6-oxopyridazin-1-yl)benzenesulfonamides as multi-target anti-inflammatory agents targeting carbonic anhydrase, COX-2 and 5-LOX enzymes: synthesis, biological evaluations and modelling insights.

Multiple inhibitions of CA, COX-2 and 5-LOX enzymes has been recognised as a useful strategy for the development of anti-inflammatory drugs that can avoid the disadvantages of using NSAIDs alone. Here, we report new pyridazine-based sulphonamides ( and ) as potential multi-target anti-inflammatory candidates. First, the furanone heterocycle in the dual CA/COX-2 inhibitor Polmacoxib was replaced with the pyridazinone one.

Evaluation of Corneal Parameters and Meibomian Gland Alterations After Corneal Cross-Linking in Patients With Progressive Keratoconus.

Objectives: The aim of the study was to evaluate the changes in corneal parameters and meibomian gland alterations after corneal cross-linking (CXL) for progressive keratoconus.

Methods: Thirty nine eyes of 39 keratoconus patients were treated with CXL. Corneal topography, specular microscopy, the Ocular Surface Disease Index© (OSDI), noninvasive tear break-up time (NITBUT), and meibography indices were evaluated preoperatively and at the first, third, and sixth months after CXL.

Is Virtual Patient Simulation Superior to Human Patient Simulation: A Randomized Controlled Study.

Virtual and human patient simulation methods offer an effective way to increase patient safety, reduce the incidence of errors, and improve clinical decision-making skills. The study was conducted to compare the effects of virtual and human patient simulation methods on performance, simulation-based learning, anxiety, and self-confidence with clinical decision-making scores of nursing students. A quasi-experimental, stratified, randomized controlled study was conducted with third-year nursing students.

Assigning pathogenicity for TAB2 variants using a novel scalable functional assay and expanding TAB2 disease spectrum.

Haploinsufficiency of TGF-beta-activated kinase 1 (MAP3K7) binding protein 2 (TAB2) has been associated with congenital heart disease and more recently multiorgan structural abnormalities. Missense variant represents a major proportion of non-synonymous TAB2 variants reported in gnomAD (295/576) and Clinvar (16/73), most of which are variants of uncertain significance (VUSs). However, interpretation of TAB2 missense variants remains challenging because of lack of functional assays.

Metal coordinating inhibitors of Rift Valley fever virus replication.

Rift Valley fever virus (RVFV) is a veterinary and human pathogen and is an agent of bioterrorism concern. Currently, RVFV treatment is limited to supportive care, so new drugs to control RVFV infection are urgently needed. RVFV is a member of the order Bunyavirales, whose replication depends on the enzymatic activity of the viral L protein.

Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults.

Background: The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials.

Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only.

The role of REV-ERB in NASH.

REV-ERBs are atypical nuclear receptors as they function as ligand-regulated transcriptional repressors. The natural ligand for the REV-ERBs (REV-ERBα and REV-ERBβ) is heme, and heme-binding results in recruitment of transcriptional corepressor proteins such as N-CoR that mediates repression of REV-ERB target genes. These two receptors regulate a large range of physiological processes including several important in the pathophysiology of non-alcoholic steatohepatitis (NASH).

Mitochondrial pyruvate carrier inhibitors improve metabolic parameters in diet-induced obese mice.

The mitochondrial pyruvate carrier (MPC) is an inner mitochondrial membrane complex that plays a critical role in intermediary metabolism. Inhibition of the MPC, especially in liver, may have efficacy for treating type 2 diabetes mellitus. Herein, we examined the antidiabetic effects of zaprinast and 7ACC2, small molecules which have been reported to act as MPC inhibitors.

Synthesis and structure activity relationship of the first class of LXR inverse agonists.

Liver X Receptors (LXRs) are members of the nuclear receptor family, and they play significant role in lipid and cholesterol metabolism. Moreover, they are key regulators of several inflammatory pathways. Pharmacological modulation of LXRs holds great potential in treatment of metabolic diseases, neurodegenerative diseases, and cancer.

Effects of Robot-Assisted Gait Training in Patients With Multiple Sclerosis: A Single-Blinded Randomized Controlled Study.

Objective: This study aims to evaluate and compare the effects of conventional and robot-assisted gait training (RAGT) programs on fatigue, mood, and quality of life in patients with multiple sclerosis who have fatigue.

Methods: In this single-blinded, randomized controlled study, 37 patients with multiple sclerosis were randomized into two groups: RAGT ( n = 18) and conventional gait training ( n = 19). The RAGT group had gait training with RoboGait, whereas the conventional gait training group received conventional physiotherapist-assisted gait training.

Naturally Occurring Genetic Variants in the Oxytocin Receptor Alter Receptor Signaling Profiles.

The hormone oxytocin is commonly administered during childbirth to initiate and strengthen uterine contractions and prevent postpartum hemorrhage. However, patients have wide variation in the oxytocin dose required for a clinical response. To begin to uncover the mechanisms underlying this variability, we screened the 11 most prevalent missense genetic variants in the oxytocin receptor () gene.

Potent antiplasmodial alkaloids from the rhizobacterium Pantoea agglomerans as hemozoin modulators.

Global health concern regarding malaria has increased since the first report of artemisinin-resistant Plasmodium falciparum (Pf) two decades ago. The current therapies suffer various drawbacks such as low efficacy and significant side effects, alarming for an urgent need of more effective and less toxic drugs with higher patient compliance. Chemical entities with natural origins become progressively attractive as new drug leads due to their structural diversity and bio-compatibility.

The Rx-HEART Framework to Address Health Equity and Racism Within Pharmacy Education.

To identify gaps in health equity and anti-racism education across the pharmacy curriculum, define the key health equity and anti-racism concepts that are suggested to be included across the pharmacy curriculum, and recommend a framework with steps to integrate health equity and anti-racism education across the pharmacy curriculum. Other professions, such as social work, nursing, and medicine, have taken steps to address social injustice by integrating anti-racism into their curriculum. The National Association of Social Workers (NASW) advocates for "social justice and social change with and on behalf of clients" and included racism and health equity in its mission to eradicate "discrimination, oppression, poverty, and other forms of social injustice.

Design, Synthesis and Antitumor Activity of Novel Dispiro[oxindole-cyclohexanone]- pyrrolidines.

Background: Spirooxindoles are privileged scaffolds in medicinal chemistry, which were identified through Wang's pioneering work as inhibitors of MDM2-p53 interactions.

Objective: To design and synthesize 2,6-diarylidenecyclohexanones and dispiro[oxindole-cyclohexanone]- pyrrolidines having potential antitumor effect.

Methods: Dispiro[oxindole-cyclohexanone]-pyrrolidines 6a-h were synthesized in a regioselective manner via 1,3-dipolar cycloaddition reaction of 2,6-diarylidenecyclohexanones 3a-h, isatin, and sarcocine.

Treatment modification after second-line failure among people living with HIV in the Asia-Pacific.

Background: The World Health Organization recommends continuation with the failing second-line regimen if third-line option is not available. We investigated treatment outcomes among people living with HIV in Asia who continued with failing second-line regimens compared with those who had treatment modifications after failure.

Methods: Treatment modification was defined as a change of two antiretrovirals, a drug class change or treatment interruption (TI), all for >14 days.

Comparison of Perioperative, Oncological, and Functional Outcomes of Three-Dimensional Versus Robot-Assisted Laparoscopic Radical Prostatectomy: A Preliminary Study.

Radical prostatectomy (RP) is the first-line treatment modality for prostate cancer and can be performed using retropubic or minimally invasive techniques. New technologies such as the da Vinci robotic system and three-dimensional (3D) laparoscopic imaging system have been developed to overcome the challenges of conventional laparoscopy. This study aimed to compare the perioperative, oncological, and functional outcomes of robot-assisted laparoscopic RP (RALP) and 3D laparoscopic RP (3D LRP).

Being a Physician in Coronavirus Disease 2019 Pandemic and Alternative Health Care Service: Telemedicine: Prospective Survey Study.

In this study, we aimed to detect anxiety levels of the physicians during the Coronavirus Disease 2019 (COVID-19) pandemic and to assess the knowledge, perspective, and willingness of the physicians about telemedicine. This was a survey study of physicians from different specialties who provided patient care during the pandemic in Turkey. A total of 824 physicians responded to questionnaire, which consisted of 5 sections: (1) demographic characteristics; (2) anxiety level; (3) knowledge; (4) perspective; and (5) willingness to use telemedicine.