Circulating brain-derived neurotrophic factor levels and heart failure: A systematic review and meta-analysis.

AIMS: Biomarkers are paramount for managing heart failure (HF) patients as prognostic and therapeutic efficacy index tools. Systemic levels of brain-derived neurotrophic factor (BDNF) can add to the HF biomarker scenario, allowing for potentiated efficacy in diagnosis, prognostic stratification, and prediction of patient response to a given therapeutic intervention because BDNF is one of the primary rulers of myocardial function. Yet, whether BDNF is a reliable clinical biomarker awaits clinical validation. Hence, we aimed to answer this relevant question via a systematic review and meta-analysis of existing studies. METHODS AND RESULTS: International databases, including PubMed, Scopus, Embase, and the Web of Science, were comprehensively searched for studies assessing BDNF levels in patients with HF versus non-HF controls or as a prognostic factor for HF complications. Data were extracted and analysed by random-effect meta-analysis. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were computed to pool the results of studies. We included 11 studies in the final review, among which six underwent meta-analysis. These studies analysed 1420 HF patients, with a mean age of 65.4 ± 11.2 years. Meta-analysis revealed that patients with HF had significantly lower circulating BDNF levels than healthy controls (SMD -2.47, 95% CI -4.39 to -0.54, P-value = 0.01). Moreover, patients with higher New York Heart Association functional classification had lower levels of BDNF. Adverse clinical outcomes such as all-cause mortality and HF rehospitalization were also associated with lower levels of BDNF in individual studies. CONCLUSIONS: BDNF levels are decreased in patients with HF. Most importantly, we observed an association between lower BDNF levels and poor prognosis in patients with HF. Our study supports BDNF as an easy-to-dose diagnostic and prognostic biomarker to be implemented in clinical practice for HF. Further studies are warranted to address this ability specifically.

Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer.

Lung cancer (LC) is the main cause of cancer-related mortality. Most LC patients are diagnosed in an advanced stage when the symptoms are obvious, and the prognosis is quite poor. Although low-dose computed tomography (LDCT) is a routine clinical examination for early detection of LC, the false-positive rate is over 90%. As one of the intensely studied epigenetic modifications, DNA methylation plays a key role in various diseases, including cancer and other diseases. Hypermethylation in tumor suppressor genes or hypomethylation in oncogenes is an important event in tumorigenesis. Remarkably, DNA methylation usually occurs in the very early stage of malignant tumors. Thus, DNA methylation analysis may provide some useful information about the early detection of LC. In recent years, liquid biopsy has developed rapidly. Liquid biopsy can detect and monitor both primary and metastatic malignant tumors and can reflect tumor heterogeneity. Moreover, it is a minimally invasive procedure, and it causes less pain for patients. This review summarized various liquid biopsies based on DNA methylation for LC. At first, we briefly discussed some emerging technologies for DNA methylation analysis. Subsequently, we outlined cell-free DNA (cfDNA), sputum, bronchoalveolar lavage fluid, bronchial aspirates, and bronchial washings DNA methylation-based liquid biopsy for the early detection of LC. Finally, the prognostic value of DNA methylation in cfDNA and sputum and the diagnostic value of other DNA methylation-based liquid biopsies for LC were also analyzed.

Mechanism research and treatment progress of NAD pathway related molecules in tumor immune microenvironment.

Nicotinamide adenine dinucleotide (NAD) is the core of cellular energy metabolism. NAMPT, Sirtuins, PARP, CD38, and other molecules in this classic metabolic pathway affect many key cellular functions and are closely related to the occurrence and development of many diseases. In recent years, several studies have found that these molecules can regulate cell energy metabolism, promote the release of related cytokines, induce the expression of neoantigens, change the tumor immune microenvironment (TIME), and then play an anticancer role. Drugs targeting these molecules are under development or approved for clinical use. Although there are some side effects and drug resistance, the discovery of novel drugs, the development of combination therapies, and the application of new technologies provide solutions to these challenges and improve efficacy. This review presents the mechanisms of action of NAD pathway-related molecules in tumor immunity, advances in drug research, combination therapies, and some new technology-related therapies.

The Function of cGAS-STING Pathway in Treatment of Pancreatic Cancer.

The activation of stimulator of interferon genes (STING) signalling pathway has been suggested to promote the immune responses against malignancy. STING is activated in response to the detection of cytosolic DNA and can induce type I interferons and link innate immunity with the adaptive immune system. Due to accretive evidence demonstrating that the STING pathway regulates the immune cells of the tumor microenvironment (TME), STING as a cancer biotherapy has attracted considerable attention. Pancreatic cancer, with a highly immunosuppressive TME, remains fatal cancer. STING has been applied to the treatment of pancreatic cancer through distinct strategies. This review reveals the role of STING signalling on pancreatic tumors and other diseases related to the pancreas. We then discuss new advances of STING in either monotherapy or combination methods for pancreatic cancer immunotherapy.