Therapeutic Benefit Research Articles

Comparative effectiveness of exercise interventions for primary dysmenorrhea: a systematic review and network meta-analysis.

Exercise is increasingly being promoted as an effective treatment for primary dysmenorrhea (PD). This study aims to conduct a comprehensive network meta-analysis (NMA) of randomized controlled trials to identify the optimal types and dosages of exercise for managing PD in women. Adhering to PRISMA-NMA guidelines, we systematically reviewed RCTs from the Cochrane Library, Web of Science, PubMed, and Embase databases up to May 23, 2024. Data analysis was performed using 'GEMTC' and 'BUGSnet' packages within a Bayesian framework in R and a hierarchy of exercise treatments was also calculated using surface under the cumulative ranking curve (SUCRA) values. Subgroup analyses were conducted to identify the most effective exercise regimens, including duration, frequency, and volume of the exercise interventions. Forty-nine studies representing 3,129 participants (1,640 exercises and 1,489 controls) were included. The results showed that all exercise interventions significantly reduced menstrual pain of the PD patients. Of six exercise intervention modalities based on the study ranked effectiveness, statistically significant reductions in pain intensity were found for resistance exercise and multi-component exercise. Multi-component exercise and stretching exercise were ranked best for menstrual symptoms, while core-strengthening exercise and multi-component exercise had the greatest impact on reducing pain duration. Significant and clinically important reductions or reliefs in pain occurred with 4 to 8 weeks of exercise training from all exercises, with resistance exercise showing the best efficacy when the duration exceeded 8 weeks, followed by multi-component exercise and mind-body exercise. Multi-component exercise and aerobic exercise with 1 to 3 sessions per week induced greater benefit in performance improvements, while resistance exercise with increased frequency showed the enhanced performance. Resistance exercise could elicit better efficacy within` 30-minute training duration, and multi-component exercise was ranked the best if such a training over 30min. This study provided quantitative insight into efficacy and effectiveness of exercise interventions on PD treatments. All six different exercises are associated with positive influence on PD management. Our study indicates that this exercise training induced adaptation may have therapeutic benefits for PD patients; however, such alterations and improvements are affected by exercise regiments.

Butyrate-Mediated Modulation of Paraoxonase-1 Alleviates Cardiorenometabolic Abnormalities in a Rat Model of Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) has been associated with cardiovascular risks and comorbid pathologies, particularly cardiorenal disorder. Short-chain fatty acids (SCFAs), especially butyrate, are essential fatty acids that regulate metabolic health and ameliorate granulosa inflammation in PCOS. However, the effect of butyrate on cardiorenal damage associated with PCOS is unknown. This study investigated the impact of SCFA and butyrate on cardiorenal abnormalities in PCOS rat model and the probable involvement of paraoxonase-1 (PON-1). Eight-week-old female Wistar rats were allotted into three groups, n = 5, namely control (CTL), PCOS (LEZ), and LEZ + BUT. Induction of PCOS with letrozole (1mg/kg) lasted for 21days, while treatment with butyrate (200mg/kg) commenced after the induction and lasted for 6weeks uninterruptedly. PCOS rats showed hyperandrogenism, multiple ovarian cysts, disrupted metabolic indices (fasting insulin and homeostatic model of insulin resistance), and increased (p < 0.05) plasma troponin T, urea, and creatinine, as well as increased cardiac/renal stroma cell-derived factor-1/caspase-6, malondialdehyde/nuclear factor-kappaB, transforming growth factor-β1, and renal ϒ-glutamyl transferase, while a significant decrease (p < 0.05) in systemic nitric oxide/endothelial nitric oxide synthase and cardiac/renal hypoxia-inducible factor-1α and nuclear factor erythroid 2-related factor 2, which were accompanied with a decreased level of PON-1. These systemic and cardiorenal derangements were reversed by butyrate administration. The results demonstrate the therapeutic benefits of SCFAs, butyrate, against cardiorenometabolic disorder in a model of PCOS. This beneficial effect is accompanied by an elevated level of PON-1. The present data possibly provides a preclinical relevance for the management of cardiorenal syndrome in PCOS.

Real-world application of disitamab vedotin (RC48-ADC) in patients withbreast cancer with different HER2 expression levels: efficacy and safety analysis.

Disitamab vedotin (RC48-ADC), an antibody-drug conjugate (ADC), combines specific antibody disitamab with cytotoxicity monomethyl auristatin E to effectively target the human epidermal growth factor receptor 2 (HER2) protein on tumor cells for precise elimination. Recent studies have demonstrated that RC48-ADC offers therapeutic benefits for patients with HER2-positive and HER2-low-expression breast cancer (BC). However, a thorough exploration of its efficacy and safety in real-world settings for patients with metastatic breast cancer (mBC) is currently lacking. This retrospective, multicenter, real-world study included patients with mBC who received RC48-ADC from September 2021 to March 2024. These patients include HER2-positive BC and HER2-low-expression BC. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), restricted mean survival time, objective response rate (ORR), and disease control rate (DCR). Factors affecting efficacy and the occurrence of treatment-related adverse events (TRAE) were evaluated. The study included a cohort of 89 patients with mBC, with 48 of those being identified as HER2-positive. As of March 2024, 22 deaths were recorded, with an immature median OS. Total PFS varied from 1.0 to 31.2 months, with a median of 5.5 months (95% CI, 4.368-6.632). HER2-positive patients exhibited prolonged PFS compared with HER2-low-expression patients (6.6 months vs 4.1 months, P = .023). The overall ORR stood at 25.8% (95% CI, 0.178-0.358), with higher rates observed in HER2-positive patients compared with HER2-low-expression patients (31.3% vs 19.5%). Similarly, the overall DCR was 78.7% (95% CI, 0.691-0.859), with HER2-positive patients demonstrating superior DCR compared with HER2-low-expression patients (83.3% vs 73.2%). Notably, HER2 expression emerged as the primary determinant of RC48-ADC efficacy. The most prevalent TRAE among all patients included leukopenia (21.3%) and alopecia (20.2%). RC48-ADC showcases promising efficacy and manageable safety in patients with both HER2-positive and HER2-low-expression mBC.

Combined therapy with pirfenidone and nintedanib counteracts fibrotic silicosis in mice.

Pneumoconiosis, especially silicosis, is a prevalent occupational disease with substantial global economic implications and lacks a definitive cure. Both pneumoconiosis and idiopathic pulmonary fibrosis (IPF) are interstitial lung diseases, which share many common physiological characteristics. Because pirfenidone and nintedanib are approved to treat IPF, their potential efficacy as antifibrotic agents in advanced silicosis deserves further exploration. Thus, we aimed to evaluate the individual and combined effects of pirfenidone and nintedanib in treating advanced silicosis mice and elucidate the underlying mechanisms of their therapeutic actions via multiomics. We administered monotherapy or combined therapy of pirfenidone and nintedanib, with low and high doses, in silicosis established after 6weeks and evaluated lung function, inflammatory responses and fibrotic status. Additionally, we employed transcriptomic and metabolomic analyses to uncover the mechanisms underlying different therapeutic strategies. Both pirfenidone and nintedanib were effective in treating advanced silicosis, with superior outcomes observed in combination therapy. Transcriptomic and metabolomic analyses revealed that pirfenidone and nintedanib primarily exerted their therapeutic effects by modulating immune responses, signalling cascades and metabolic processes involving lipids, nucleotides and carbohydrates. Furthermore, we experimentally validated both monotherapy and combined therapy yielded therapeutic benefits through two common signalling pathways: steroid biosynthesis and purine metabolism. In conclusion, pirfenidone and nintedanib, either individually or in combination, demonstrate substantial potential in advanced silicosis. Furthermore, combined therapy outperformed monotherapy, even at low doses. These therapeutic benefits are attributed to their influence on diverse signalling pathways and metabolic processes.

The Impact of Human-Animal Interaction on Animal Welfare and Owners’ Job Performance: A Study on Cats, Dogs and Birds

ABSTRACT Human-Animal Interaction (HAI) has been significant since ancient times, initially with animals, especially dogs, assisting in hunting and food gathering. Over time, this relationship evolved into domestication, companionship, and therapeutic roles in society. In urban areas, pet ownership is widespread, driven by companionship, therapeutic benefits, and social status. This study focuses on urban pet owners due to structured work environments, allowing a clear examination of the relationship between HAI, animal welfare, and work performance. The study explores HAI's dual impact on animal welfare and the work performance of dog, cat, and bird owners. Key factors include psychological, social, and physical closeness in HAI; animal hygiene, physical activity, and loneliness for welfare; and work performance for owners. Data were collected from 404 pet-owning employees in Istanbul, with statistical analyses confirming tool validity. Results reveal a significant positive correlation (r = 0.568) between HAI and animal welfare, and a positive but smaller correlation (r = 0.215) between HAI and work performance. Findings support HAI's role in enhancing well-being, suggesting pet-friendly policies in workplaces to maximize benefits.

TET2 regulates early and late transitions in exhausted CD8+ T cell differentiation and limits CAR T cell function.

CD8+ T cell exhaustion hampers control of cancer and chronic infections and limits chimeric antigen receptor (CAR) T cell efficacy. Targeting TET2 in CAR T cells provides therapeutic benefit; however, TET2's role in exhausted T cell (TEX) development is unclear. In chronic lymphocytic choriomeningitis virus (LCMV) infection, TET2 drove conversion from stem cell-like TEX progenitors toward terminally differentiated and effector (TEFF)-like TEX. TET2 also enforced a terminally differentiated state in the early bifurcation between TEFF and TEX, indicating broad roles for TET2 in acquisition of effector biology. To exploit the therapeutic potential of TET2, we developed clinically actionable TET2-targeted CAR T cells by disrupting TET2 via knock-in of a safety switch alongside CAR knock-in at the TRAC locus. TET2-targeted CAR T cells exhibited restrained terminal exhaustion in vitro and enhanced antitumor responses in vivo. Thus, TET2 regulates fate transitions in TEX differentiation and can be targeted with a safety mechanism in CAR T cells for improved tumor control.

Bariatric and endo-bariatric interventions for diabetes: What is the current evidence?

Bariatric interventions have shown the best therapeutic benefits in individuals with obesity. They can be classified into surgical procedures (bariatric/metabolic surgery) and endoscopic procedures. Common surgical procedures include sleeve gastrectomy, Roux-en-Y gastric bypass, bilio-pancreatic diversion with or without duodenal switch and Stomach Intestinal Pylorus Sparing Surgery. Endoscopic procedures include intragastric balloons, transpyloric shuttle, endoscopic gastroplasties, aspiration therapy, duodenal mucosal resurfacing, duodeno-jejunal bypass liner, gastro-duodeno-jejunal bypass and incisionless magnetic anastomosis system among others. However, these procedures are limited by lack of wide availability, high costs, immediate and long-term complications and poor acceptability in some regions. Weight re-gain is a common concern and revisional metabolic surgery is often required. Appropriate pre-operative evaluation and correction of nutritional deficiencies post-surgery are very important. The most appropriate procedure for a person would depend on multiple factors like the intended magnitude of weight-loss, comorbidities and surgical fitness, as well as choice of the patient. Recently, glucagon-like insulinotropic peptide-1 receptor agonists (GLP) and the GLP-1/gastric inhibitory polypeptide co-agonist–Tirzepatide have shown remarkable weight loss potential, which is at par with bariatric interventions in some patients. How far these can help in avoiding invasive bariatric procedures in near future remains to be explored. An updated and comprehensive clinical review by He et al in the recent issue of World Journal of Diabetes address has addressed the avenues and challenges of currently available bariatric surgeries which will enable clinicians to make better decisions in their practice, including their applicability in special populations like the elderly and pediatric age groups, type 1 diabetes mellitus, and non-diabetics.

Extracellular vesicles derived from endothelial progenitor cells modified by Houshiheisan promote angiogenesis and attenuate cerebral ischemic injury via miR-126/PIK3R2.

Angiogenesis following cerebral ischemia is crucial for restoring blood supply to the ischemic region. Extracellular vesicles (EVs) derived from endothelial progenitor cells (EPCs) offer potential therapeutic benefits in the treatment of cerebral ischemia. Houshiheisan (HSHS) has been shown to improve clinical outcomes in ischemic stroke patients, reduce cerebral ischemic damage in rats, and protect endothelial cells. However, the potential effects of HSHS-modified EPC-derived EVs (EVsHSHS) for cerebral ischemia remain unexplored. This study investigated the impact of EVsHSHS on angiogenesis using rats with permanent middle cerebral artery occlusion (pMCAO) and brain microvascular endothelial cells (BMECs) subjected to oxygen-glucose deprivation (OGD). Results demonstrated that EVsHSHS promoted the proliferation, migration, and tube formation of BMECs in vitro. In vivo, high doses of EVsHSHS exhibited better performance than equivalent doses of unmodified EPC-derived EVs in reducing cerebral infarction volume, improving cortical blood perfusion, decreasing neurological deficit scores, and increasing cortical microvessel density at day 7 post-modeling. The pro-angiogenic effects of EVsHSHS following cerebral ischemia were associated with the regulation of miR-126 and the PIK3R2/PI3K/AKT pathway.

Change in self-construal: a repertory grid technique study of women admitted to a Mother and Baby Unit

IntroductionPregnancy and the postnatal period represent a time of heightened risk for women to experience mental health difficulties. Some mothers may require specialist inpatient psychiatric support made available through Mother and Baby units (MBUs). Although there is evidence of the therapeutic benefits of MBUs, many studies have utilised methodologies vulnerable to interviewer and social desirability biases. The repertory grid technique (RGT), derived from personal construct theory (PCT), has been successfully used to explore how the way in which a person thinks about and defines the self (i.e., self-construal) changes following therapeutic intervention in samples of people experiencing mental health conditions. Therefore, this study aimed to explore change in maternal self-construal following MBU admission, utilising the RGT, thereby enhancing our understanding for the therapeutic role of MBU admissions in women’s mental health recoveries.MethodsParticipants were recruited from two MBUs in England. RGT was undertaken with participants shortly after admission and again at discharge, allowing for comparisons between grids to assess change in how a mother viewed herself in relation to certain aspects of the self (e.g., ideal self) and other people, a concept referred to as construing in PCT. Data were analysed using principal component analysis, Slater analysis, and content analysis.ResultsThere were 12 participants who completed repertory grids at admission, with eight (66.67%) participants also completing discharge grids. Most of the eight participants demonstrated improvements in overall self-esteem and self-esteem as a mother, a shift towards a more positive self-perception, and increased construed similarity between the self and positively construed others, and construing became more varied. Conversely, a few participants displayed a reduction in self-esteem, particularly in the maternal role and increased construed similarity between the self and negatively construed others, and construing became more rigid.ConclusionsAll participants exhibited changes to construing during their MBU admission, with most participants displaying positive changes to self-esteem and self-perception and a more adaptive process of construing. Potential implications are offered for service users, families, clinicians, and stakeholders. Recommendations for future research are also provided.

Recovery Horizons: Nature-Based Activities as Adjunctive Treatments for Co-Occurring Post-Traumatic Stress Disorder and Substance Use Disorders

Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) frequently co-occur, and individuals with co-occurring PTSD and SUD often experience more complex treatment challenges and poorer outcomes compared to those with either condition alone. Integrative treatment approaches that simultaneously address both PTSD and SUD are considered the most effective and include both pharmacological and non-pharmacological strategies. In recent years, complementary interventions have garnered increased attention due to their broad appeal and potential therapeutic benefits in enhancing existing treatments for PTSD and SUD. This review explores the existing literature on the use of nature-based activities, such as hiking, camping, sailing, and surfing in treating individuals with co-occurring PTSD and SUD. Nature-based activities offer promising adjunctive benefits, including the reduction of PTSD symptoms and craving levels. While evidence supports the therapeutic value of nature-based activities, current research remains limited. Further research is needed to better understand their therapeutic role and to refine their implementation in clinical practice.

Hormonal interventions in skin wounds - a mini review.

The ability to heal from wounds is perhaps the most important biological function that ensures our survival and perpetuation. Cutaneous wound healing typically consists of four characteristic stages, namely hemostasis, inflammation, proliferation, and remodeling, which are carefully carried out by coordinated actions of various cells, cytokines, and hormones. Incoordination of these steps may impede complete and efficient reconstruction and functional recovery of wounds or even lead to worsened outcomes. Hormones, as powerful modulators of organ functions, participate in multiple steps of the wound healing process and play a pivotal role by choreographing the complex interplay of cellular and molecular events. Leveraging the regulatory effects of hormones to enhance the healing process, hormonal therapy has emerged as a promising approach in the clinical treatment of wounds. Current research has focused on determination of the optimal dosages, delivery methods, and combinations of hormonal therapies to maximize their therapeutic benefits while minimizing potential side effects. This review highlights the molecular mechanisms, clinical benefits and side effects of the most commonly used hormones in clinical treatment of wounds.

Protective effect of maltol on pathological response of cardiomyocyte in dystrophic mice.

Heart diseases are a significant contributor to global morbidity and mortality, and despite their diverse and complex mechanisms, treatment options remain limited. Maltol, a natural compound with antioxidant and anti-inflammatory activities, exhibits potential for addressing this need. This study evaluates the cardioprotective effects of maltol in isoproterenol (ISO)-induced cardiac stress models and Duchenne muscular dystrophy (DMD). Maltol's cardiac cytotoxicity was assessed in rodent (H9c2) and human (AC16) cells and compared with that of dapagliflozin to illustrate its cardiac safety. In ISO-induced stress models, maltol significantly reduced hypertrophic markers and inflammation while enhancing autophagy and antioxidant pathways. In the mdx mice, a DMD model, maltol treatment improved cardiac contractility and reduced pathogenic remodeling. Enhanced phosphorylation of phospholamban and trends toward higher SERCA2a expression indicated enhanced Ca2+ handling, which is crucial in DMD cardiomyopathy. This study demonstrated that maltol has the potential to provide therapeutic benefits for DMD and other cardiac conditions characterized by hypertrophy and inflammation, as evidenced by its well-known antioxidant properties, low cytotoxicity, and capacity to enhance cardiac function and Ca2+ handling.

Rosuvastatin activates autophagy via inhibition of the Akt/mTOR axis in vascular smooth muscle cells.

The proliferation and migration of vascular smooth muscle cells (VSMCs) are key contributors to the development of atherosclerosis and restenosis. We investigated the impact of rosuvastatin (RSV) on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, with a focus on the Akt/mTOR-autophagy signaling pathways. The cytotoxicity of RSV was assessed using MTT and annexin V staining, while the proliferation and migration capabilities of PDGF-BB-induced VSMCs were evaluated using MTT and cell migration assays. Confocal microscopy was employed to examine autophagic cell images, and protein expressions were analyzed via Western blotting. Our key findings revealed that RSV inhibited PDGF-BB-induced proliferation and migration of VSMCs, significantly reducing the expression of proliferating cell nuclear antigen and matrix metalloproteinase-2, which are crucial for these processes. RSV also enhanced autophagy in PDGF-BB-stimulated cells by inducing the maturation of microtubule-associated protein light chain 3 and increasing the expression of Beclin-1, autophagy related (Atg)3, Atg5, and Atg7. The regulatory effects of RSV on PDGF-BB-induced autophagy, proliferation, and migration were associated with the suppression of the Akt/mTOR signaling pathway. These findings suggest that RSV may have potential therapeutic benefits in preventing and treating vascular diseases by targeting the Akt/mTOR pathway and inducing autophagy.

"Instead of Building More Buildings, They Should Plant More Trees", a Photovoice Study of Determinants of Happiness and Sadness Among East London Adolescents.

Globally, mental health problems in adolescents, alongside associated morbidity and mortality, have never been higher. Local living, working and environmental conditions, socio-economics, and intra-individual and inter-individual processes impact mental health. The risk of developing mental health problems is higher in certain areas, including East London. However, limited research explores East London adolescents' experiences of mental health. An in-depth and locally situated understanding of determinants shaping East London adolescents' happiness and sadness is needed. This study used Photovoice, a qualitative method within a community-based participatory research methodology, to generate photographic and textual data, which was analyzed using reflexive thematic analysis. This method allows participants to be part of knowledge production and authors to present the data. Our findings underscore the bidirectional interplay between environmental factors and adolescents' happiness and sadness. Gratitude for nature was described as increasing happiness: adolescents connected to nature to memories, appreciation, and leisure opportunities. Adolescents were concerned about the fragility of nature in response to urban development. The urban environment was perceived as imposing, inspiring, and offering therapeutic benefits blighted by pollution. Beautiful areas were described as paradisical and lacking, revealing urban development and economic productivity disparities. Our research documents the voices of an under-researched group, revealing novel insights while empowering adolescents as co-producers of mental health research. This study indicates participatory research is valuable for granting adolescents autonomy and addressing misrepresentation. The findings implicate multiple stakeholders, including "Health in All Policies." By deepening our understanding of adolescent mental health in East London, our study can be leveraged to bolster the effectiveness and relevance of interventions for East London adolescents.

Therapeutic Potential of Neutralizing Monoclonal Antibodies (nMAbs) against SARS-CoV-2 Omicron Variant.

The COVID-19 pandemic has spurred significant endeavors to devise treatments to combat SARS-CoV-2. A limited array of small-molecule antiviral drugs, specifically monoclonal antibodies and interferon therapy, have been sanctioned to treat COVID-19. These treatments typically necessitate administration within ten days of symptom onset. There have been reported reductions in the effectiveness of these medications due to mutations in non-structural protein genes, particularly against Omicron subvariants. This underscores the pressing requirement for healthcare systems to continually monitor pathogen variability and its impact on the efficacy of prevention and treatments. This review aimed to comprehend the therapeutic benefits and recent progress of nMAbs for preventing and treating the Omicron variant of SARS-CoV-2. Neutralizing monoclonal antibodies (nMAbs) provide a treatment avenue for severely affected individuals, especially those at high risk for whom vaccination is not viable. With their specific epitope affinity, they pose no significant risk of severe adverse effects. The degree of reduction in neutralization varies significantly across different monoclonal antibodies and variant combinations. For instance, Sotrovimab maintained its neutralization effectiveness against Omicron BA.1, but exhibited diminished efficacy against BA.2, BA.4, BA.5, and BA.2.12.1. Bebtelovimab has been observed to preserve its efficacy against all subtypes of the Omicron variant. Subsequently, WKS13, mAb-39, 19n01, F61-d2 cocktail, etc., have become effective. This review has highlighted the therapeutic implications of nMAbs in SARS-CoV-2 Omicron treatment and the progress of COVID-19 drug discovery.

OGC SO31 - Treatment of cachexia in gastric cancer: A literature review exploring the use of natural anti-inflammatory products and their derivatives

Abstract Background Gastric cancer is a major cause of global cancer-related mortality, with 5-year survival rates of 7% in advanced disease. Cancer cachexia, characterised by irreversible skeletal muscle loss driven by systemic inflammation, contributes to approximately 20% of cancer-related deaths. Cachexia differs from malnutrition in that it cannot be fully reversed with nutritional support alone. Current treatments that focus on nutritional support, psychological counselling and anti-inflammatory medication are lacking in efficacy. Natural dietary supplements and their derivatives such as fatty acids, probiotics, amino acids, curcumin, ginger and resveratrol, may offer additional therapeutic benefits in managing gastric cancer cachexia. Method A comprehensive literature review was conducted to evaluate the efficacy of natural anti-inflammatory products in managing gastric cancer cachexia. The review focused on widely studied compounds including omega-3 fatty acids, probiotics, amino acids, curcumin, fucoidan, epigallocatechin-3-gallate (EGCG), resveratrol and ginger, assessing their impact on inflammation, muscle mass preservation, and overall patient outcomes. Results Natural anti-inflammatory compounds demonstrate efficacy in mitigating cancer cachexia by reducing systemic inflammation and muscle wasting. Essential fatty acids from nuts, seeds, and fish oil decrease pro-inflammatory cytokines and improve chemotherapy tolerance. Probiotics reduce gut dysbiosis and may enhance chemotherapy tolerance. Essential amino acids may promote muscle anabolism and reduce catabolism. Curcumin, fucoidan, EGCG and ginger exhibit anti-inflammatory properties, with some improving appetite and reducing nausea. While promising, these compounds need further clinical trials to validate their efficacy and safety in cancer cachexia management. Conclusion Natural anti-inflammatory products hold promise as adjunctive therapies in management of gastric cancer cachexia. While preclinical evidence is encouraging, robust clinical trials are essential to confirm their efficacy and safety. Integrating these compounds with conventional treatments may offer a comprehensive approach to addressing the complex metabolic and inflammatory challenges of cancer cachexia, potentially improving patient outcomes. Future research should focus on understanding mechanisms, optimising dosages, and overcoming bioavailability challenges.

Targeting Glucose Metabolism: A Novel Therapeutic Approach for Parkinson’s Disease

Glucose metabolism is essential for the maintenance and function of the central nervous system. Although the brain constitutes only 2% of the body weight, it consumes approximately 20% of the body’s total energy, predominantly derived from glucose. This high energy demand of the brain underscores its reliance on glucose to fuel various functions, including neuronal activity, synaptic transmission, and the maintenance of ion gradients necessary for nerve impulse transmission. Increasing evidence shows that many neurodegenerative diseases, including Parkinson’s disease (PD), are associated with abnormalities in glucose metabolism. PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, accompanied by the accumulation of α-synuclein protein aggregates. These pathological features are exacerbated by mitochondrial dysfunction, oxidative stress, and neuroinflammation, all of which are influenced by glucose metabolism disruptions. Emerging evidence suggests that targeting glucose metabolism could offer therapeutic benefits for PD. Several antidiabetic drugs have shown promise in animal models and clinical trials for mitigating the symptoms and progression of PD. This review explores the current understanding of the association between PD and glucose metabolism, emphasizing the potential of antidiabetic medications as a novel therapeutic approach. By improving glucose uptake and utilization, enhancing mitochondrial function, and reducing neuroinflammation, these drugs could address key pathophysiological mechanisms in PD, offering hope for more effective management of this debilitating disease.

The Bi-Steric Inhibitor RMC-5552 Reduces mTORC1 Signaling and Growth in Lymphangioleiomyomatosis.

Mutations in the Tuberous Sclerosis Complex (TSC) genes result in the hyperactivation of the mechanistic/mammalian target of rapamycin 1 (mTORC1) growth pathway in mesenchymal pulmonary cells. Rapamycin (SirolimusTM), a naturally occurring macrolide, is the only therapeutic approved for women with lymphangioleiomyomatosis (LAM), a progressive, destructive lung disease caused by TSC gene mutations and mTORC1 hyperactivation. However, on cessation of the drug, lung function decline continues. We demonstrated here that pulmonary LAM cancer stem-like cells (SLS) most highly expressed the eukaryotic translation initiation factor 4E (eIF4E)-dependent translation initiation genes. We also showed that the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) gene has the lowest expression in these cells, indicating that the 4E-BP1/eIF4E ratio in LAM SLS cells favors unrestrained eIF4E oncogenic mRNA translation. The bi-steric mTORC1-selective compound RMC-5552 prevented growth of LAM-associated fibroblasts (LAFs) and phosphorylation of proteins in the ribosomal protein S6K1/ribosomal protein S6 (S6K1/S6) and 4E-BP1/eIF4E translation mTORC1-driven pathways, whereas rapamycin only blocked the S6K/S6 axis. Rapamycin inhibition of LAF growth was rapidly reversed, but RMC-5552 inhibition was more durable. RMC-5552, through its potential to eradicate LAM cancer SLS cells, may have therapeutic benefit in LAM and other diseases with mTORC1 hyperactivity.

Frexalimab(SAR441344) as a potential multi-autoimmune disorder tackling mAB targeting the CD40-CD40L pathway undergoing clinical trials: A Review

Autoimmune disorders exhibit intricate pathology. Their mechanisms are complex, which attenuates the need for novel therapeutic interventions. Frexalimab, a potent monoclonal antibody targeting the dysregulated CD40-CD40L pathway, stands out as a formidable weapon against the assault of inflammation and tissue devastation. Diverse electronic databases were searched using relevant keywords to extract data on the role of Frexalimab in combating various autoimmune diseases. This review highlights Frexalimab’s efficacy in improving various disability indicators of relapsing multiple sclerosis (RMS), alleviating fatigue in primary Sjögren’s syndrome (PSJS), and improving glycemic control in diabetic patients. Across multiple trials, its favorable safety profile has proven its superiority over first-generation drugs in minimizing side effects. Indeed, Frexalimab has become a harbinger of hope in the fight against autoimmune diseases and has pioneered a unique and unchallenging way for tackling complex autoimmune diseases in the clinical realm, however, further large-scale trials are needed to establish its therapeutic benefits across different autoimmune conditions.

An ayurvedic approach to the management of Fissure-in-ano: A case Study

Background: In today's sedentary lifestyle, coupled with unhealthy dietary habits and stress, digestive disorders such as Fissure-in-ano have become prevalent. Fissure-in-ano is a longitudinal tear in the anal canal, most commonly occurring in the posterior midline, characterized by severe pain, burning sensation, and occasional bleeding. In Ayurveda, this condition aligns with Parikartika, often caused by improper administration of therapies like Basti (enema) or Virechana (purgative). Case Study: It explores the efficacy of per rectal Administration of Kaseesadi Taila for the management of Parikartika in a 35-year-old female patient presenting with anal pain, burning, and rectal bleeding post-defecation. Materials &amp; Methods: It involved daily rectal Administration of Kaseesadi Taila (10ml) for 7 days. Results: It showed significant improvement by day 3, with complete relief of symptoms and healing of the fissure by day 7. The therapeutic benefits of Kaseesadi Taila are attributed to its Lekhana (scraping), Shodhana (cleansing), and Ropana (healing) properties, which promote wound healing, reduce inflammation, and facilitate easier bowel movements. Conclusion: Kaseesadi Taila is an effective, cost-efficient treatment for fissure-in-ano, providing significant symptom relief without the drawbacks of conventional surgical interventions.