The tumor microenvironment is a complex system that is affected by various factors, including hypoxia, acidosis, and immune and inflammatory responses, which have significant effects on tumor adhesion, invasion, metastasis, angiogenesis, and autophagy. In this hostile tumor microenvironment, autophagy of tumor cells can promote tumor growth and metastasis. As autophagy is a double-edged sword in tumors, treatment of cancer via regulation of autophagy is extremely complicated. Therefore, understanding the relationship between tumor autophagy and the tumor microenvironment is extremely important. As the immune milieu plays an important role in tumor development, immunotherapy has become a promising form of cancer therapy. A multi-pronged treatment approach using immunotherapy and molecular targets may become the major direction for future cancer treatments. This article reviews existing knowledge regarding the immune factors in the tumor microenvironment and the status of tumor autophagy research.

Polycystic ovary syndrome (PCOS) is a common condition, affecting 5–10% of women of reproductive age worldwide. It has serious reproductive implications and causes mood disorders and metabolic disorders, such as type-2 diabetes. Because PCOS reflects multiple abnormalities, there is no single drug that can treat all its symptoms. Existing pharmaceutical agents, such as oral contraceptives (OCs), are suggested as a first-line therapy for menstrual irregularities; however, OCs are not appropriate for women pursuing pregnancy. Additionally, insulin-sensitizing agents, which appear to decrease insulin levels and hyperandrogenemia in women with PCOS, have been associated with a high incidence of gastrointestinal adverse effects. It is a common practice in Chinese society to receive traditional Chinese medicine (TCM) for treatment of gynecological problems and infertility. Current research demonstrates that several herbs and herbal formulas show beneficial effects in PCOS treatment. In this study, we conducted the first large-scale survey through the Taiwan National Health Insurance Program database to analyze TCM utilization patterns among women with PCOS in Taiwan during 1997–2010. The survey results revealed that 89.22% women with newly diagnosed PCOS had received TCM therapy. Jia-Wei-Xiao-Yao-San and Xiang-Fu (Rhizoma Cyperi) were the most commonly used formula and single herb, respectively, in the database. In addition, we found that the top five commonly prescribed single herbs and herbal formulas have shown promise in treating symptoms associated with PCOS.

Cardiomyopathy is a group of heterogeneous cardiac diseases that impair systolic and diastolic function, and can induce chronic heart failure and sudden cardiac death. Cardiomyopathy is prevalent in the general population, with high morbidity and mortality rates, and contributes to nearly 20% of sudden cardiac deaths in younger individuals. Genetic mutations associated with cardiomyopathy play a key role in disease formation, especially the mutation of sarcomere encoding genes and ATP kinase genes, such as titin, lamin A/C, myosin heavy chain 7, and troponin T1. Pathogenesis of cardiomyopathy occurs by multiple complex steps involving several pathways, including the Ras-Raf-mitogen-activated protein kinase-extracellular signal-activated kinase pathway, G-protein signaling, mechanotransduction pathway, and protein kinase B/phosphoinositide 3-kinase signaling. Excess biomechanical stress induces apoptosis signaling in cardiomyocytes, leading to cell loss, which can induce myocardial fibrosis and remodeling. The clinical features and pathophysiology of cardiomyopathy are discussed. Although several basic and clinical studies have investigated the mechanism of cardiomyopathy, the detailed pathophysiology remains unclear. This review summarizes current concepts and focuses on the molecular mechanisms of cardiomyopathy, especially in the signaling from mutation to clinical phenotype, with the aim of informing the development of therapeutic interventions.

Background/Aim: Despite recent advances in EGFR-tyrosine kinase inhibitor (TKI) drugs for glioblastoma multiforme (GBM), intrinsic EGFR alterations in GBM have resulted in drug resistance and unsatisfactory clinical development of EGFR-TKIs. Determining the unknown mechanisms underlying EGFR-TKI drug resistance is an urgent, but unmet, medical need for GBM. Although several m⁶A RNA methylation regulators, such as reader YTHDF1/2, were recently predicted to be related to GBM recurrence, none was associated with resistance to the 3^rd generation EGFR-TKI osimertinib. Materials and Methods: Osimertinib-resistant GBM cells (U87^OSR) were established to ascertain the correlation between m⁶A expression and osimertinib resistance, prior to systemic analyses on m⁶A writers, erasers, and readers. YTHDF3-silencing was employed to reveal changes in IC₅₀, cellular migration, cancer stemness, and p21-guided senescence in U87^OSR cells. Signaling pathways and an in vivo xenograft model of U87^OSR cells were investigated to delineate the influence of osimertinib-resistance and elevated YTHDF3 expression. Results: YTHDF3 played a crucial role in inducing cellular proliferation, migration, and stemness in U87^OSR GBM cells. Importantly, silencing of YTHDF3 markedly reduced the activation of certain signaling pathways, including EGFR- or ITGA7- AKT, and ERK in U87^OSR cells. Our study also revealed the oncogenic function of YTHDF3 in inducing senescence escape via p21 down-regulation. In contrast, silencing of YTHDF3 resulted in increased p21 expression, senescence, and suppressed tumor growth in our osimertinib-resistant preclinical model. Conclusion: Overall, our research underscores the novel potential of YTHDF3 as a new pharmacological target in GBM treatment, specifically for patients with osimertinib-resistant or refractory tumors.

Early diagnosis and identification of prognostic markers for ovarian cancer can significantly improve survival and reduce mortality. The role of the YME1L1 signaling axis in genetic alterations and immune infiltration of the tumor microenvironment remains unclear. Bioinformatics web resources, including GEPIA2, cBioPortal, Oncomine, Kaplan-Meier Plotter, and TIMER, were used to analyze the expression profile, prognostic value, and immune infiltration of YME1L1. We further performed a tissue microarray analysis of paraffin-embedded tissues from 60 patients with ovarian cancer, recorded at the FIGO/TNM cancer staging. Here, we used multi-omics analysis of multiple histological datasets to map the role of epigenetic and genetic alterations of YME1L1 in tumor immune infiltration and the prognosis of cancer patients. We explored YME1L1 gene expression profiles by systematically analyzing the association between YME1L1 expression and the prognosis of patients with ovarian cancer confirmed in multiple databases. High expression levels of YME1L1 were associated with poor overall and disease-free survival. Together, our studies suggest that YME1L1 may modulate tumor survival and immune features and contribute to tumor immune invasion, poor prognosis, and immunotherapy failure. Our findings may have clinical implications for the design of treatment strategies, prognosis assessment, and follow-up management of patients receiving immunotherapy for various cancers.