Unlocking c-MET: A comprehensive journey into targeted therapies for breast cancer.

Breast cancer is the most common malignancy among women, posing a formidable health challenge worldwide. In this complex landscape, the c-MET (cellular-mesenchymal epithelial transition factor) receptor tyrosine kinase (RTK), also recognized as the hepatocyte growth factor (HGF) receptor (HGFR), emerges as a prominent protagonist, displaying overexpression in nearly 50% of breast cancer cases. Activation of c-MET by its ligand, HGF, secreted by neighboring mesenchymal cells, contributes to a cascade of tumorigenic processes, including cell proliferation, metastasis, angiogenesis, and immunosuppression. While c-MET inhibitors such as crizotinib, capmatinib, tepotinib and cabozantinib have garnered FDA approval for non-small cell lung cancer (NSCLC), their potential within breast cancer therapy is still undetermined. This comprehensive review embarks on a journey through structural biology, multifaceted functions, and intricate signaling pathways orchestrated by c-MET across cancer types. Furthermore, we highlight the pivotal role of c-MET-targeted therapies in breast cancer, offering a clinical perspective on this promising avenue of intervention. In this pursuit, we strive to unravel the potential of c-MET as a beacon of hope in the fight against breast cancer, unveiling new horizons for therapeutic innovation.

A State-of-the-Art Review on the Recent Advances of Mesenchymal Stem Cell Therapeutic Application in Systematic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with an unknown etiology that has widespread clinical and immunological manifestations. Despite the increase in knowledge about the pathogenesis process and the increase in treatment options, however, the treatments fail in half of the cases. Therefore, there is still a need for research on new therapies. Mesenchymal stem cells (MSCs) are powerful regulators of the immune system and can reduce the symptoms of systemic lupus erythematosus. This study aimed to review the mechanisms of immune system modulation by MSCs and the role of these cells in the treatment of SLE. MSCs suppress T lymphocytes through various mechanisms, including the production of transforming growth factor-beta (TGF-B), prostaglandin E2 (PGE2), nitric oxide (NO), and indolamine 2 and 3-oxygenase (IDO). In addition, MSCs inhibit the production of their autoantibodies by inhibiting the differentiation of lymphocytes. The production of autoantibodies against nuclear antigens is an important feature of SLE. On the other hand, MSCs inhibit antigen delivery by antigen-presenting cells (APCs) to T lymphocytes. Studies in animal models have shown the effectiveness of these cells in treating SLE. However, few studies have been performed on the effectiveness of this treatment in humans. It can be expected that new treatment strategies for SLE will be introduced in the future, given the promising results of MSCs application.

Importance of gut microbiota metabolites in the development of cardiovascular diseases (CVD).

Cardiovascular disease (CVD) remains the most common cause of death worldwide and has become a public health concern. The proven notable risk factors for CVD are atherosclerosis, hypertension, diabetes, dyslipidemia, inflammation, and some genetic defects. However, research has shown a correlation between metabolic health, gut microbiota, and dietary risk factors. The gut microbiota makes an important contribution to human functional metabolic pathways by contributing enzymes that are not encoded by the human genome, for instance, the breakdown of polysaccharides, polyphenols and vitamins synthesis. TMAO and SCFAs, human gut microbiota compounds, have respective immunomodulatory and pro-inflammatory effects. Choline and l-carnitine are abundant in high-fat diets and are transformed into TMA by gut bacteria. The liver's phase of metabolism then changes TMA into TMAO. In turn, TMAO promotes the activation of macrophages, damages vascular endothelium, and results in CVD-however, dysbiosis decreases SCFAs and bile acids, which raises intestinal permeability. Congestion in the portal vein, a drop in cardiac output, a reduction in intestinal perfusion, and intestinal leakage are all caused by heart failure. These factors induce systemic inflammation by increasing intestinal leakage. By raising CRP and pro-inflammatory reactions, human gut dysbiosis and elevated TMAO levels promote the development of arterial plaque, hasten the beginning of atherosclerosis, and raise the risk of CAD. A healthy symbiosis between the gut microbiota and host is a key factor in shaping the biochemical profile of the diet, therefore which are crucial for maintaining the intestinal epithelial barrier, growing mucosa, reducing inflammation, and controlling blood pressure.

Gastrointestinal Tract, Microbiota and Multiple Sclerosis (MS) and the Link Between Gut Microbiota and CNS.

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by central nervous system (CNS) lesions that can lead to severe neurological defects. Evidence is mounting that immune function is crucial in neuroinflammatory illnesses like MS. Through its impact on systemic immunological reactions, the large microbial population known as the gut microbiota has been linked to both human health and disease. The gut-brain axis (GBA) therefore encompasses neurological, immunological, and hormonal pathways, and microbiota can have a number of effects on the immune system, influencing MS. Recent research revealed a bidirectional relationship between metabolites originating from the gut microbiota, namely short-chain fatty acids (SCFAs). Intestinal epithelial cells are influenced by SCFAs, which also boosts the secretion of -Defensins and regenerating islet-derived III (REGIII) proteins. These proteins reduce intestinal pathogens, induce T-reg differentiation, and modulate immune responses by reducing IL-1 and IL-6 expression and increasing IL-10. Nutrition and psychological stress are two of the most significant elements that can directly and indirectly change the microbiota compositions along with other environmental influencing factors. An important regulator of intestinal physiology in the gut-brain-microbiota axis is butyrate, a well-known SCFA. Intestinal dysbiosis, altered intestinal barrier function, behavioral abnormalities, and activation of the hypothalamic-pituitary-adrenal (HPA) axis are all brought on by exposure. Probiotics, bacterial metabolite supplementation, fecal matter transplantation, defined microbial communities, and dietary intervention are some methods for modifying the composition of the gut microbiota that may be used to affect disease-related immune dysfunction and serve as the foundation for a new class of therapeutics.

Mate-value and relationship satisfaction: The moderating roles of mate retention behaviors.

Previous research indicates that mate retention strategies are associated with mate value and affect relationship satisfaction. The current research aimed to replicate previous findings in a non-WEIRD society (Iran) and to extend this research by investigating the moderating roles of individual and coalitional mate retention. Participants (n = 754; 416 women) in a committed, heterosexual relationship from two independent samples reported (1) their relationship satisfaction, (2) their partner's mate value, (3) the frequency of performing individual mate retention, and (4) the frequency of requesting coalitional mate retention. Results indicated that there were positive associations between mate value, individual and coalitional Benefit-Provisioning mate retention behaviors, and relationship satisfaction. We found negative associations between individual and coalitional Cost-Inflicting mate retention behaviors and relationship satisfaction. We found that mate retention moderated the relationship between mate value and relationship satisfaction. Limitations of the current study are noted, and future directions are discussed.

Review of Pharmaceutical and Therapeutic Approaches for Type 2 Diabetes and Related Disorders.

Type 2 diabetes (T2D), which affects many people around the world, is one of the diseases that is on the rise. Various studies have revealed that insulin resistance and lessened insulin production have been associated with T2D, and they also show that this disease can have a genetic origin and is associated with different genes, such as KCNQ1, PPAR-γ, calpain-10, ADIPOR2, TCF7L2, which can be utilized as therapeutic targets. Different therapeutic approaches and strategies such as exercise and diet, pharmacological approaches, and utilization of nanoparticles in drug delivery and gene therapy can be effective in the treatment and control of T2D. Glucagon-like peptide 1 (GLP-1) and sodiumglucose cotransporter-2 (SGLT2) have both been considered as drug classes in the treatment of T2D and T2D-related diseases such as cardiovascular disease and renal disease, and have considerable influences such as diminished cardiovascular mortality in individuals with T2D, ameliorated postprandial glycaemia, ameliorated fasting glycaemia, and diminished bodyweight on disease treatment and improvement process. In the present review article, we have attempted to explore the risk factors, genes, and diseases associated with T2D, therapeutic approaches in T2D, the influences of drugs such as dapagliflozin, metformin, acarbose, Januvia (sitagliptin), and ertugliflozin on T2D in clinical trials and animal model studies. Research in clinical trials has promising results that support the role of these drug approaches in T2D prophylaxis and ameliorate safety even though additional clinical research is still obligatory.

Adaptation and Psychometric Properties of the Persian Version of the Coalitional Mate Retention Inventory (CMRI).

Mate retention behaviors are designed to reduce the likelihood of partner infidelity and relationship withdrawal. We investigated the psychometric properties of the Persian translation of The Coalitional Mate Retention Inventory (CMRI) in Iran and explored the sex differences in the performance frequencies of these behaviors. Participants in a committed heterosexual romantic relationship (n = 508, 270 female and 238 male) were drawn from a community sample. Participants reported demographic information (including age, duration of relationship), the Persian translation of CMRI, and the Persian translation of the Mate Retention Inventory-Short Form. The results of the confirmatory factor analyses demonstrated a good fit of the CMRI seven-factor model and achieved good reliability for CMRI and its subscales. We further documented sex differences in the frequency with which coalitional mate retention behaviors were performed. The results revealed that CMRI is a valuable instrument for assessing mate retention across diverse cultures.