Therapeutics, Volume 2, Issue 3 (September 2025) – 6 articles

Background: The outgrowth of castration-resistant prostate cancer (CRPC) dictates patient morbidity and mortality. Recurrence of prostate cancer (PC) following androgen-deprivation therapy (ADT) often occurs due to constitutively active androgen receptor (AR) splice variants (AR-Vs), primarily AR-V7. Therefore, safe and effective therapies enabling the suppression of both full-length AR (AR-FL) and AR-Vs are urgently needed. The natural compound dimethyl sulfoxide (DMSO) has negligible cytotoxicity at concentrations below 5% and has anticancer potential. DMSO has been broadly used in biomedical research as a solvent for pharmaceuticals, as a cryoprotectant for cells, and as a topical treatment to suppress pain and inflammation. We investigated the effect of low-dose DMSO on AR expression, cell viability, and metastatic ability in PC cell lines expressing both AR-FL and AR-V7 (e.g., 22Rv1) and those expressing only AR-FL (e.g., C4-2B). Methods: MTT cell viability assays were performed to measure DMSO-induced cytotoxicity. Wound-healing assays were conducted to monitor the effect of DMSO on the migratory phenotype of cancer cells. Western blot analyses were performed to study the efficacy of DMSO in suppressing the protein levels of AR-FL and AR-V7, and expression of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) was measured as a possible mechanism. Results: At concentrations of 0.1–1% (v/v), DMSO treatment showed minimal cytotoxicity, whereas the highest concentration used (2.5%) showed approximately 20% cytotoxicity at 96 h. Interestingly, however, DMSO treatment at concentrations of 1.0 and 2.5% significantly inhibited the migration of PC cells. Treatment with DMSO led to a dose-dependent inhibition of both AR-FL and AR-V7. Notably, in 22Rv1 cells, DMSO potently downregulated the expression of hnRNPH1, a splicing factor often associated with AR expression and signaling. Conclusions: Our findings suggest that low concentrations of DMSO may have potential as an effective anticancer agent, both at the initial and later stages when PC cells become castration resistant. Full article

Background/Objectives: Gender-affirming surgery (GAS) is associated with improved mental health outcomes in transgender and gender-diverse (TGD) individuals. However, TGD populations experience disproportionately high rates of substance use disorders (SUDs), which are established risk factors for surgical complications. Despite this, the relationship between preoperative SUDs and postoperative outcomes following GAS has not been studied. Our objective was to evaluate how specific SUD subtypes, including tobacco, alcohol, and cannabis, impact short- and medium-term postoperative complications following GAS. Methods: A retrospective cohort study was conducted using the TriNetX Research Network, which includes de-identified electronic health records from over 100 million U.S. patients. Adults with documented gender dysphoria who underwent GAS between April 2015 and April 2025 were included. Patients were divided into four groups: no SUD, tobacco use, alcohol use, and cannabis use. Propensity score matching was used to control for demographic variables. Postoperative complications were assessed at 30 days and 6 months. Results: Alcohol use was significantly associated with increased rates of delayed wound healing, wound dehiscence, gastrointestinal symptoms, and postoperative pain at both 30 days and 6 months. Cannabis use was linked to higher rates of wound dehiscence, infections, GI symptoms, and pain. Tobacco use showed the broadest impact, significantly associated with nearly all complications measured except pain at 30 days. These associations persisted at six months. Conclusions: This is the first study to quantify the relationship between substance use and GAS outcomes. Preoperative use of tobacco, alcohol, and cannabis was independently associated with increased postoperative complications. These findings underscore the need for systematic preoperative screening and the development of SUD-specific perioperative care pathways to improve outcomes and advance equity in surgical care for TGD patients. Full article

Background: Multiple Chemical Sensitivity (MCS) is a complex, disabling condition marked by non-specific symptoms in response to low-level chemical exposures. It often leads to substantial impairments in quality of life, psychological health, and daily functioning. Although non-pharmacological approaches—such as lifestyle and psychological interventions—are widely used, their clinical effectiveness remains unclear. Objective: We aim to evaluate the effectiveness of lifestyle-based approaches in improving clinical and psychosocial outcomes in adults with Multiple Chemical Sensitivity. Methods: A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420251013537). Literature searches were carried out in MEDLINE (PubMed), CINAHL, Google Scholar, and ResearchGate between March and April 2025. Eligible studies included adults (≥18 years) with a confirmed diagnosis of MCS and reported outcomes such as perceived stress, anxiety, depressive symptoms, or quality of life. Methodological quality and risk of bias were independently assessed using the PEDro scale, NIH Quality Assessment Tool, CEBMa checklist, and Cochrane RoB 2.0. Results: Twelve studies (N = 378) met the inclusion criteria. Cognitive and behavioral therapies demonstrated the most consistent evidence of efficacy, with reductions in symptom severity, maladaptive cognitive patterns, and functional limitations. Mindfulness-based stress reduction showed favorable outcomes, while other mindfulness-based interventions yielded mixed results. Exposure-based therapies contributed to increased chemical tolerance and reduced avoidance behavior. Electromagnetic and biomedical approaches demonstrated preliminary but limited effectiveness. Aromatherapy was well tolerated and perceived as relaxing, though its clinical impact was modest. Conclusions: Cognitive and behavioral therapies appear to be most effective among lifestyle-based interventions for MCS/IEI. However, study heterogeneity limits the generalizability of findings, underscoring the need for more rigorous research. Full article

Background and Aims: Gastroesophageal reflux disease (GERD) is the most common esophageal disorder worldwide and a progressive condition leading to Barrett’s esophagus and adenocarcinoma. Continuous medical therapy with proton pump inhibitors fails to restore the antireflux barrier and is unable to relieve symptoms in up to 40% of patients. A tailored and standardized antireflux surgical procedure may increase cure rates and meet patient expectations. Methods and Results: Antireflux surgery aims to reestablish the natural antireflux barrier, which includes the diaphragmatic crura, the lower esophageal sphincter (LES), and the angle of His along with the gastroesophageal flap valve. For decades, the Nissen total fundoplication has been the primary procedure and remains the gold standard for surgical treatment. Alternatives such as Toupet partial fundoplication, Dor partial fundoplication, and the magnetic sphincter augmentation (LINX™) procedure have been developed to mitigate side effects like dysphagia, gas-bloat syndrome, and the inability to belch or vomit. Recent clinical findings regarding a novel procedure, RefluxStop™, indicate that restoring the gastroesophageal flap valve, in conjunction with anterior fundoplication and a silicone device for stabilizing the LES beneath the diaphragm, can achieve lasting reflux control and enhance patient-reported outcomes. Conclusions: The planning of healthcare services and actionable strategies to improve equity and quality of treatment is critical to address the global burden of GERD. Modern laparoscopic surgery for GERD is safe and effective and should be performed in centers offering a complete diagnostic pathway and specific surgical techniques tailored to the individual GERD phenotype. Shared decision-making between the surgeon and the patient is essential for the choice of operation. A personalized approach can offer clinical benefits over total fundoplication and improve patient-reported outcomes. Full article

Background: Human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) allow for high-throughput evaluation of cardiomyocyte (CM) physiology in health and disease. While multimodality testing provides a large breadth of information related to electrophysiology, contractility, and intracellular signaling in small populations of iPSC-CMs, current technologies for analyzing these parameters are expensive and resource-intensive. Methods: We have designed a novel 2D/3D hybrid organoid system that can harness optical imaging techniques to assess electromechanical properties and calcium dynamics across CMs in a high-throughput manner. We validated our methods using a doxorubicin-based system, as the drug has well-characterized cardiotoxic, pro-arrhythmic effects. Results: This novel hybrid system provides the functional benefit of 3D organoids while minimizing optical interference from multilayered cellular systems through our cell-culture techniques that propagate organoids outwards into 2D iPSC-CM sheets. The organoids recapitulate contractile forces that are more robust in 3D structures and connectivity, while 2D CMs facilitate analysis at an individual cellular level, which recreated numerous doxorubicin-induced electrophysiologic and propagation abnormalities. Conclusions: Thus, we have developed a novel 2D/3D hybrid organoid model that employs an integrated optical analysis platform to provide a reliable high-throughput method for studying cardiotoxicity, providing valuable data on calcium, contractility, and signal propagation. Full article

Animal models are indispensable in biomedical research, offering critical insights into disease mechanisms and therapeutic strategies. However, existing models often inadequately replicate human pathophysiology, leading to discrepancies between preclinical and clinical outcomes. Despite their contributions, many models exhibit significant limitations, especially concerning cancer and infectious diseases. Inaccurate modeling of human biological responses can result in failed clinical trials, escalated research costs, and delays in developing effective treatments. The golden hamster (Mesocricetus auratus) has emerged as a viable model, particularly in cancer and infectious disease research. Sharing physiological and immunological profiles similar to humans, the golden hamster offers distinct advantages over other rodent models, such as mice and rats. This review explores the benefits of using golden hamsters in cancer research, highlighting their contributions to scientific advancements while also addressing the limitations due to incomplete immunological and molecular knowledge about this species. Full article