Association of systemic inflammation markers in cancer mortality with diabetes: evidence from National Health and Nutrition Examination Survey.

AIMS: Inflammation plays a crucial role in the interconnection between diabetes and cancer. Our study seeks to investigate the predictive value of inflammatory indices concerning overall survival (OS) among diabetic cancer patients. METHODS: We analyzed data from the National Health and Nutrition Examination Survey between 1999 and 2020. Using four immune-related markers, we employed the log-rank method, multivariate Cox regression, and subgroup analysis to explore the predictive capacity of these markers for OS among adult individuals with diabetes and cancer. RESULTS: Our study identified four systemic immune-inflammatory indices that demonstrated significant predictive potential for OS among diabetic cancer patients, namely systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (all p values < 0.05). Notably, these inflammatory biomarkers still maintain their predictive value after adjusting potential confounding factors. The analysis using restrictive cubic splines revealed significant non-linear relationships between inflammatory biomarkers and OS. CONCLUSION: The findings presented in this study underscore the potential of inflammatory markers as prognostic indicators and their crucial role in enhancing risk assessment for diabetic patients with cancer.

Relationship between hemoglobin and lung cancer: evidence from Mendelian randomization and National Health and Nutrition Examination Survey

Background Lung cancer is the primary cause of cancer-related mortality worldwide. Hemoglobin (Hb) represents the most widely utilized test parameter in clinical settings. However, few articles have examined the causal relationship between Hb concentration and lung cancer incidence. Methods Mendelian randomization (MR) was first conducted to investigate the potential causality between Hb and lung cancer. Sensitivity analyses were applied to validate the reliability of MR results. Then, the National Health and Nutrition Examination Survey (NHANES) database was used to verify the effect of Hb on the prognosis of lung cancer. Results The MR analysis demonstrated that Hb was casually associated with the decreased risk of lung cancer in the European population (ORIVW 0.84, 95% CI 0.75–0.95, p = 0.006; ORWeighted-median 0.78, 95% CI 0.65–0.94, p = 0.008; ORMR-Egger 0.82, 95% CI 0.64–1.04, p = 0.11). The results from the NHANES database showed that a high value of Hb was associated with better outcomes for patients with lung cancer (HR 0.45, 95% CI 0.26–0.79, p = 1.6E−03). Conclusions Our study provides further evidence for the relationship between Hb levels and lung cancer, highlighting the potential significance of Hb as a biomarker for predicting the risk and prognosis of lung cancer (AU)

FHL2 promotes the aggressiveness of lung adenocarcinoma by inhibiting autophagy via activation of the PI3K/AKT/mTOR pathway.

BACKGROUND: Increasing evidence indicates that four and a half LIM domains 2 (FHL2) plays a crucial role in the progression of various cancers. However, the biological functions and molecular mechanism of FHL2 in lung adenocarcinoma (LUAD) remain unclear. METHODS: We evaluated the prognostic value of FHL2 in LUAD using public datasets and further confirmed its prognostic value with our clinical data. The biological functions of FHL2 in LUAD were evaluated by in vitro and in vivo experiments. Pathway analysis and rescue experiments were subsequently performed to explore the molecular mechanism by which FHL2 promoted the progression of LUAD. RESULTS: FHL2 was upregulated in LUAD tissues compared to adjacent normal lung tissues, and FHL2 overexpression was correlated with unfavorable outcomes in patients with LUAD. FHL2 knockdown significantly suppressed the proliferation, migration and invasion of LUAD cells, while FHL2 overexpression had the opposite effect. Mechanistically, FHL2 upregulated the PI3K/AKT/mTOR pathway and subsequently inhibited autophagy in LUAD cells. The effects FHL2 on the proliferation, migration and invasion of LUAD cells are dependent on the inhibition of autophagy, as of induction autophagy attenuated the aggressive phenotype induced by FHL2 overexpression. CONCLUSIONS: FHL2 promotes the progression of LUAD by activating the PI3K/AKT/mTOR pathway and subsequently inhibiting autophagy, which can be exploited as a potential therapeutic target for LUAD.

Relationship between hemoglobin and lung cancer: evidence from Mendelian randomization and National Health and Nutrition Examination Survey.

BACKGROUND: Lung cancer is the primary cause of cancer-related mortality worldwide. Hemoglobin (Hb) represents the most widely utilized test parameter in clinical settings. However, few articles have examined the causal relationship between Hb concentration and lung cancer incidence. METHODS: Mendelian randomization (MR) was first conducted to investigate the potential causality between Hb and lung cancer. Sensitivity analyses were applied to validate the reliability of MR results. Then, the National Health and Nutrition Examination Survey (NHANES) database was used to verify the effect of Hb on the prognosis of lung cancer. RESULTS: The MR analysis demonstrated that Hb was casually associated with the decreased risk of lung cancer in the European population (ORIVW 0.84, 95% CI 0.75-0.95, p = 0.006; ORWeighted-median 0.78, 95% CI 0.65-0.94, p = 0.008; ORMR-Egger 0.82, 95% CI 0.64-1.04, p = 0.11). The results from the NHANES database showed that a high value of Hb was associated with better outcomes for patients with lung cancer (HR 0.45, 95% CI 0.26-0.79, p = 1.6E-03). CONCLUSIONS: Our study provides further evidence for the relationship between Hb levels and lung cancer, highlighting the potential significance of Hb as a biomarker for predicting the risk and prognosis of lung cancer.

New insights of miRNA molecular mechanisms in breast cancer brain metastasis and therapeutic targets.

Brain metastases in breast cancer (BC) patients are often associated with a poor prognosis. Recent studies have uncovered the critical roles of miRNAs in the initiation and progression of BC brain metastasis, highlighting the disease's underlying molecular pathways. miRNA-181c, miRNA-10b, and miRNA-21, for example, are all overexpressed in BC patients. It has been shown that these three miRNAs help tumors grow and metastasize by targeting genes that control how cells work. On the other hand, miRNA-26b5p, miRNA-7, and miRNA-1013p are all downregulated in BC brain metastasis patients. They act as tumor suppressors by controlling the expression of genes related to cell adhesion, angiogenesis, and invasion. Therapeutic miRNA targeting has considerable promise in treating BC brain metastases. Several strategies have been proposed to modulate miRNA expression, including miRNA-Mimics, antagomirs, and small molecule inhibitors of miRNA biogenesis. This review discusses the aberrant expression of miRNAs and metastatic pathways that lead to the spread of BC cells to the brain. It also explores miRNA therapeutic target molecular mechanisms and BC brain metastasis challenges with advanced strategies. The targeting of certain miRNAs opens a new door for the development of novel therapeutic approaches for this devastating disease.

Emerging functions and clinical applications of exosomal microRNAs in diseases.

Exosomes are an important group of extracellular vesicles that transfer several kinds of biomolecules and facilitate cell-cell communication. The content of exosomes, particularly the amounts of microRNA (miRNAs) inside these vesicles, demonstrates a disease-specific pattern reflecting pathogenic processes and may be employed as a diagnostic and prognostic marker. miRNAs may enter recipient cells through exosomes and generate a RISC complex that can cause degradation of the target mRNAs or block translation of their corresponding proteins. Therefore, exosome-derived miRNAs constitute an important mechanism of gene regulation in recipient cells. The miRNA content of exosomes can be used as an important tool in the detection of diverse disorders, particularly cancers. This research field has an important situation in cancer diagnosis. In addition, exosomal microRNAs offer a great deal of promise in the treatment of human disorders. However, there are still certain challenges to be resolved. The most important challenges are as follow: the detection of exosomal miRNAs should be standardized, exosomal miRNAs-associated studies should be conducted in large number of clinical samples, and experiment settings and detection criteria should be consistent across different labs. The goal of this article is to present an overview of the effects of exosome-derived microRNAs on a variety of diseases, including gastrointestinal, pulmonary, neurological, and cardiovascular diseases, with a particular emphasis on malignancies.

The significance of N6-methyladenosine-modified non-coding RNAs in different disorders.

N6-methyladenosine (m6A) is the most widespread endogenous modification affecting the expression of eukaryotic mRNA transcripts. Recent studies have shown that the m6A marks within non-coding RNAs can affect their functions and expression in a manner similar to that of mRNA-coding genes. Since non-coding RNAs are involved in the pathophysiology of several disorders, identification of the role of m6A marks in the regulation of expression of non-coding RNAs can open a new era for identifying underlying mechanisms of several disorders and designing novel therapeutic modalities for a variety of disorders, particularly cancers. Moreover, a number of non-coding RNAs can affect m6A levels. In the current review, we discuss the impacts of m6A marks on the expression of non-coding RNAs in the context of different disorders, such as bone, gastrointestinal, neurologic, renal, pulmonary, hepatic and other disorders.