Receptor tyrosine kinases (RTKs) are cell surface receptors with kinase activity that play a crucial role in diverse cellular processes. Among the RTK family members, Human epidermal growth factor receptor 2 (HER2) and HER3 are particularly relevant to breast cancer. The review delves into the complexities of receptor tyrosine kinase interactions, resistance mechanisms, and the potential of anti-HER3 drugs, offering valuable insights into the clinical implications and future directions in this field of study. It assesses the potential of anti-HER3 drugs, such as pertuzumab, in overcoming resistance observed in HER2-positive breast cancer therapies. The review also explores the resistance mechanisms associated with various drugs, including trastuzumab, lapatinib, and PI3K inhibitors, providing insights into the intricate molecular processes underlying resistance development. The review concludes by emphasizing the necessity for further clinical trials to assess the efficacy of HER3 inhibitors and the potential of developing safe and effective anti-HER3 treatments to improve treatment outcomes for patients with HER2-positive breast cancer.

Aortic stenosis (AS) is very common in mid-aged and elderly patients, and it has been reported to have a negative impact on both short and long-term survival with a high mortality rate. The current study identified methods of diagnosis, incidence, and causes of AS, pathogenesis, intervention and management and future perspectives of Asymptomatic and Symptomatic Aortic stenosis. A systematic literature search was conducted using PubMed, Scopus and CINAHL, using the Mesh terms and key words \"Aortic stenosis\", \"diagnostic criteria\", \"pathogenesis\", \"incidence and causes of AS\" and\" intervention and management strategies\". Studies were retained for review after meeting strict inclusion criteria that included studies evaluating Asymptomatic and Symptomatic AS. Studies were excluded if duplicate publication, overlap of patients, subgroup studies of a main study, lack of data on AS severity, case reports and letters to editors. Forty-five articles were selected for inclusion. Incidence of AS across the studies ranged from 3 % to 7 %. Many factors have been associated with incidence and increased risk of AS, highest incidence of AS was described after aortic valve calcification, rheumatic heart disease, degenerative aortic valve disease, bicuspid aortic valve and other factors. AS is common and can be predicted by aortic root calcification volume, rheumatic heart disease, degenerative aortic valve disease, bicuspid aortic valve. Intervention and management for AS patients is a complex decision that takes into consideration multiple factors. On the other hand, there is not enough progress in preventive pharmacotherapy to slow the progression of AS.

Cutaneous Squamous Cell Carcinoma (cSCC) is a common and potentially fatal type of skin cancer that poses a significant threat to public health and has a high prevalence rate. Exposure to ultraviolet radiation on the skin surface increases the risk of cSCC, especially in those with genetic syndromes like xerodermapigmentosum and epidermolysis bullosa. Therefore, understanding the molecular pathogenesis of cSCC is critical for developing personalized treatment approaches that are effective in cSCC. This article provides a comprehensive overview of current knowledge of cSCC pathogenesis, emphasizing dysregulated signaling pathways and the significance of molecular profiling. Several limitations and challenges associated with conventional therapies, however, are identified, stressing the need for novel therapeutic strategies. The article further discusses molecular targets and therapeutic approaches, i.e., epidermal growth factor receptor inhibitors, hedgehog pathway inhibitors, and PI3K/AKT/mTOR pathway inhibitors, as well as emerging molecular targets and therapeutic agents. The manuscript explores resistance mechanisms to molecularly targeted therapies and proposes methods to overcome them, including combination strategies, rational design, and optimization. The clinical implications and patient outcomes of molecular-targeted treatments are assessed, including response rates and survival outcomes. The management of adverse events and toxicities in molecular-targeted therapies is crucial and requires careful monitoring and control. The paper further discusses future directions for therapeutic advancement and research in this area, as well as the difficulties and constraints associated with conventional therapies.

Chronic obstructive pulmonary disease (COPD) is marked by both lung-related and systemic symptoms, notably chronic inflammation. Despite pulmonary rehabilitation (PR) being a critical treatment for COPD, its influence on systemic inflammation remains unclear. This meta-analysis was conducted to assess PR\'s effect on circulating inflammatory markers in COPD patients. We systematically reviewed databases like PubMed, EMBASE, and Web of Science to select randomized controlled trials and observational studies that investigated the impact of PR on systemic inflammation. We calculated the mean differences (MD) in inflammatory markers before and after PR using a random-effects model and assessed the risk of bias with established tools. Our study included six investigations (four RCTs, two observational) with 147 COPD patients. Our findings show notable increases in IL-6 (MD 0.44, 95% CI 0.17-0.70, P = 0.001), CRP (MD 0.56, 95% CI 0.31-0.81, P<0.00001), and TNF-alpha (MD 0.41, 95% CI 0.12-0.70, P = 0.005) following PR. However, sensitivity analysis pinpointed the study by El-Kader et al. as a key influence on these results. Excluding this study led to nonsignificant changes. Thus, our meta-analysis uncovers an unanticipated rise in inflammatory markers post-PR in COPD patients, questioning the assumed anti-inflammatory benefits of PR.

Cancer is a major cause of death globally, and traditional treatments often have limited efficacy and adverse effects. Immunotherapy has shown promise in various malignancies but is less effective in tumors with low immunogenicity or immunosuppressive microenvironment, especially sarcomas. Tertiary lymphoid structures (TLSs) have been associated with a favorable response to immunotherapy and improved survival in cancer patients. However, the immunological mechanisms and clinical significance of TLS in malignant tumors are not fully understood. In this review, we elucidate the composition, neogenesis, and immune characteristics of TLS in tumors, as well as the inflammatory response in cancer development. An in-depth discussion of the unique immune characteristics of TLSs in lung cancer, breast cancer, melanoma, and soft tissue sarcomas will be presented. Additionally, the therapeutic implications of TLS, including its role as a marker of therapeutic response and prognosis, and strategies to promote TLS formation and maturation will be explored. Overall, we aim to provide a comprehensive understanding of the role of TLS in the tumor immune microenvironment and suggest potential interventions for cancer treatment.

Acute myeloid leukemia (AML) is a clonal hematological malignancy with high mortality rates. The identification of novel markers is urgent for AML. Cytohesins are a subfamily of guanine nucleotide exchange factors activating the ADP-ribosylation factor family GTPases. While the important roles of cytohesins have been reported in various cancers, their function in AML remains unclear. The present study aimed to explore the prognostic impact of cytohesin-4 (CYTH4) and the underlying molecular functions. RNA sequencing and AML clinical data were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases to investigate gene expression and survival. Using the R software, differentially expressed genes were identified between the high- and the low-CYTH4 group. Functional enrichment analysis was conducted by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analyses. The CIBERSORTx tool was used to explore the proportions of different immune cell types. The molecular function of CYTH4 was also validated in vitro by examining cell growth, cell cycle, apoptosis and colony-forming ability. CYTH4 was significantly upregulated in AML compared with other cancers and normal tissues. High CYTH4 expression was associated with high white blood count (P=0.004) and higher risk status (P<0.001). Patients with high CYTH4 expression had poor overall survival (OS; HR=2.19; 95% CI, 1.40-3.44; P=0.0006; high vs. low) and event-free survival (EFS; HR=2.32; 95% CI, 1.43-3.75; P=0.0006; high vs. low), and these patients could benefit from transplantation (HR=0.29; 95% CI, 0.18-0.47; P<0.0001; transplantation vs. chemotherapy). Multivariate analysis showed that high CYTH4 expression was independently associated with inferior OS (HR=2.49; 95% CI, 1.28-4.83; P=0.007) and EFS (HR=2.56; 95% CI, 1.48-4.42; P=0.001). Functional analysis showed that CYTH4 was involved in immunoregulation. In vitro validation showed knockdown of CYTH4 adversely affected cell growth and induced cell apoptosis, while overexpression of CYTH4 enhanced cell growth. Taken together, CYTH4 is expressed at high levels in AML and can potentially function as a prognostic biomarker.

BACKGROUND: Breast infiltrating ductal carcinoma (BIDC) represents the largest heterotypic tumor group, and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.
OBJECTIVE: To analyze the expression profiles and clinical implications of forkhead box M1 (FOXM1), cyclooxygenase-2 (COX-2), and glucose-regulated protein 78 (GRP78) in BIDC.
METHODS: A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis. The peripheral blood FOXM1, COX-2, and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined. Additionally, we investigated the diagnostic value of FOXM1, COX-2, and GRP78 in patients with BIDC and their correlations with clinicopathological features. Furthermore, BIDC patients were followed for 1 year to identify factors influencing patient prognosis.
RESULTS: The levels of FOXM1, COX-2, and GRP78 were significantly higher in BIDC patients compared to healthy controls (P < 0.05), and a positive correlation was observed among them (P < 0.05). Receiver operating characteristic analysis demonstrated that FOXM1, COX-2, and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC (P < 0.05). Subsequently, we found significant differences in FOXM1, COX-2, and GRP78 levels among patients with different histological grades and metastasis statuses (with vs without) (P < 0.05). Cox analysis revealed that FOXM1, COX-2, GRP78, increased histological grade, and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC (P < 0.001).
CONCLUSIONS: FOXM1, COX-2, and GRP78 exhibit abnormally high expression in BIDC, promoting malignant tumor development and closely correlating with prognosis. These findings hold significant research implications for the future diagnosis and treatment of BIDC.

Malignant brain tumors are highly heterogeneous tumors with a poor prognosis and a high morbidity and mortality rate in both children and adults. The cancer stem cell (CSC, also named tumor-initiating cell) model states that tumor growth is driven by a subset of CSCs. This model explains some of the clinical observations of brain tumors, including the almost unavoidable tumor recurrence after initial successful chemotherapy and/or radiotherapy and treatment resistance. Over the past two decades, strategies for the identification and characterization of brain CSCs have improved significantly, supporting the design of new diagnostic and therapeutic strategies for brain tumors. Relevant studies have unveiled novel characteristics of CSCs in the brain, including their heterogeneity and distinctive immunobiology, which have provided opportunities for new research directions and potential therapeutic approaches. In this review, we summarize the current knowledge of CSCs markers and stemness regulators in brain tumors. We also comprehensively describe the influence of the CSCs niche and tumor microenvironment on brain tumor stemness, including interactions between CSCs and the immune system, and discuss the potential application of CSCs in brain-based therapies for the treatment of brain tumors.

We conducted a global-scale study to identify H. pylori antimicrobial-resistant genes (ARG), address their global distribution, and understand their effect on the antimicrobial resistance (AMR) phenotypes of the clinical isolates. We identified ARG using several well-known tools against extensive bacterial ARG databases, then analyzed their correlation with clinical antibiogram data from dozens of patients across countries. This revealed that combining multiple tools and databases, followed by manual selection of ARG from the annotation results, produces more conclusive results than using a single tool or database alone. After curation, the results showed that H. pylori has 42 ARG against 11 different antibiotic classes (16 genes related to single antibiotic class resistance and 26 genes related to multidrug resistance). Further analysis revealed that H. pylori naturally harbors ARG in the core genome, called the \'Set of ARG commonly found in the Core Genome of H. pylori (ARG-CORE)\', while ARG-ACC-the ARG in the accessory genome-are exclusive to particular strains. In addition, we detected 29 genes of potential efflux pump-related AMR that were mostly categorized as ARG-CORE. The ARG distribution appears to be almost similar either by geographical or H. pylori populations perspective; however, some ARG had a unique distribution since they tend to be found only in a particular region or population. Finally, we demonstrated that the presence of ARG may not directly correlate with the sensitive/resistance phenotype of clinical patient isolates but may influence the minimum inhibitory concentration phenotype.

Cancer represents a significant and persistent global health burden, with its impact underscored by its prevalence and devastating consequences. Whereas numerous oncogenes could contribute to cancer development, a group of transcription factors (TFs) are overactive in the majority of tumors. Targeting these TFs may also combat the downstream oncogenes activated by the TFs, making them attractive potential targets for effective antitumor therapeutic strategy. One such TF is yin yang 1 (YY1), which plays crucial roles in the development and progression of various tumors. In preclinical studies, YY1 inhibition has shown efficacy in inhibiting tumor growth, promoting apoptosis, and sensitizing tumor cells to chemotherapy. Recent studies have also revealed the potential of combining YY1 inhibition with immunotherapy for enhanced antitumor effects. However, clinical translation of YY1-targeted therapy still faces challenges in drug specificity and delivery. This review provides an overview of YY1 biology, its role in tumor development and progression, as well as the strategies explored for YY1-targeted therapy, with a focus on their clinical implications, including those using small molecule inhibitors, RNA interference, and gene editing techniques. Finally, we discuss the challenges and current limitations of targeting YY1 and the need for further research in this area.