PNAS-4 is a novel pro-apoptosis gene identified latetly. In recent years, there has been a large number of research reports on the basic studies about PNAS-4 in cancer gene therapy and gene therapy of PNAS-4 alone or combined with chemotherapy or radiotherapy manifested a good application prospect, but its molecular mechanisms to promote apoptosis is not clear yet. In this paper, recent research about PNAS-4 in cancer gene therapy is briefly reviewed, and recent hypotheses on its molecular mechanisms to promote apoptosis are especially elucidated. Based on its newly identified characteristics of structural domain, we made a point that PNAS-4 might regulate functions of some target protein related to apoptosis by deSumoylation as a new deSumoylating isopeptidase, and consequently promote apoptosis.
Endogenous adult neural stem cells are closely related to the normal physiological functions of the brain and many neurodegenerative diseases. Neurons are affected by factors such as extracellular microenvironment and intracellular signaling. In recent years, some specific signaling pathways have been found that affect the occurrence of neural stem cells in adult neural networks, including proliferation, differentiation, maturation, migration, and integration with host functions. In this paper, we summarize the signals and their molecular mechanisms, including the related signaling pathways, neurotrophic factors, neurotransmitters, intracellular transcription factors and epigenetic regulation of neuronal differentiation from both the extracellular and intracellular aspects, providing basic theoretical support for the treatment of central nervous system diseases through neural stem cells approach.
ObjectiveAlthough evidence links idiopathic pulmonary fibrosis (IPF) and diabetes mellitus (DM), the exact underlying common mechanism of its occurrence is unclear. This study aims to explore further the molecular mechanism between these two diseases. MethodsThe microarray data of idiopathic pulmonary fibrosis and diabetes mellitus in the Gene Expression Omnibus (GEO) database were downloaded. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify co-expression genes related to idiopathic pulmonary fibrosis and diabetes mellitus. Subsequently, differentially expressed genes (DEGs) analysis and three public databases were employed to analyze and screen the gene targets related to idiopathic pulmonary fibrosis and diabetes mellitus. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Metascape. In addition, common microRNAs (miRNAs), common in idiopathic pulmonary fibrosis and diabetes mellitus, were obtained from the Human microRNA Disease Database (HMDD), and their target genes were predicted by miRTarbase. Finally, we constructed a common miRNAs-mRNAs network by using the overlapping genes of the target gene and the shared gene. ResultsThe results of common gene analysis suggested that remodeling of the extracellular matrix might be a key factor in the interconnection of DM and IPF. Finally, hub genes (MMP1, IL1R1, SPP1) were further screened. miRNA-gene network suggested that has-let-19a-3p may play a key role in the common molecular mechanism between IPF and DM. ConclusionsThis study provides new insights into the potential pathogenic mechanisms between idiopathic pulmonary fibrosis and diabetes mellitus. These common pathways and hub genes may provide new ideas for further experimental studies.
Obesity is a prevalent metabolic disorder,which seriously affects human health and has become the world's public health problem. Kinase S6K1, an important downstream effector of mammalian target of rapamycin (mTOR), influences specific pathological responses, including obesity, type 2 diabetes and cancer. Presently, S6K1 has become an attractive therapeutic target in the treatment of these disorders. Here, the functions of kinase S6K1, its molecular regulation mechanisms, related pathogenesis of disease and relevant small molecular inhibitors are reviewed. Finally, the prospect of research toward S6K1 is expected as well.
At present, the potential hazards of infrasound on heart health have been identified in previous studies, but a comprehensive review of its mechanisms is still lacking. Therefore, this paper reviews the direct and indirect effects of infrasound on cardiac function and explores the mechanisms by which it may induce cardiac abnormalities. Additionally, in order to further study infrasound waves and take effective preventive measures, this paper reviews the mechanisms of cardiac cell damage caused by infrasound exposure, including alterations in cell membrane structure, modulation of electrophysiological properties, and the biological effects triggered by neuroendocrine pathways, and assesses the impact of infrasound exposure on public health.
Objective To analyze the characteristics and changing trends of lung cancer-related projects funded by National Natural Science Foundation of China (NSFC) during 2019–2023, providing a reference for researchers in topic selection and for optimizing scientific research management and resource allocation. Methods Relevant databases, including the NSFC Big Data Knowledge Management Service Platform, were systematically searched to collect information on lung cancer-related funded projects from 2019 to 2023. Quantitative methods were applied to evaluate project categories, funding amounts, and the distribution of host institutions. Project themes were classified according to their titles, keywords, and abstracts, and were subsequently compared with those of projects funded during 2014–2018. Results A total of 1 327 lung cancer-related projects were funded from 2019 to 2023, with total funding of 554.92 million yuan. The Young Scientists Fund and the General Program accounted for 90.3% (1 199/1 327) of the projects and 84.1% (46 675/55 492) of the total funding; the top 10 host institutions comprised approximately 32.0% of all funded projects. Thematic analysis revealed that the core funding directions in the lung cancer field during 2019–2023 focused on molecular mechanisms and signaling pathways. Major research themes included metastasis and recurrence, tumor microenvironment and immunity, and targeted therapy resistance and drug development. Compared with 2014–2018, the proportion of projects focused on tumor microenvironment and immunity, as well as artificial intelligence and medical engineering, increased substantially. Overall, the themes of funded lung cancer projects were dominated by mechanistic studies and demonstrated cross-cutting features intersecting with disease progression, therapeutic resistance, immune regulation, and clinical translation. Conclusion The number of NSFC-funded lung cancer-related projects has continued to grow. Research themes have evolved from pure mechanistic exploration toward immune regulation and translational research, exhibiting characteristics of interdisciplinary integration with emerging technologies and multi-theme cross-fertilization. Researchers are encouraged to align with policy orientations and to emphasize the innovation and translational value of their proposed topics.
ObjectiveTo systematically summarize the molecular mechanisms, multimodal localization, and genetic stratification-based management strategies of primary hyperparathyroidism (PHPT), and to offer theoretical references for the precision diagnosis and treatment of PHPT. MethodRelevant literature on the molecular mechanisms, multimodal localization, and genetic stratification-based treatment of PHPT was retrieved from domestic and international databases and systematically reviewed. ResultsThe pathogenesis of PHPT involves cell cycle dysregulation driven by MEN1 and CCND1, impaired negative feedback of calcium homeostasis resulting from mutations in the CaSR (calcium-sensing receptor) and GNA11 (guanine nucleotide-binding protein subunit alpha-11), and the risks of malignant transformation associated with CDC73 mutations. Combined ultrasonography and radionuclide imaging can significantly enhance preoperative localization accuracy. Four-dimensional computed tomography (CT) yields high localization success rates for solitary parathyroid adenomas, whereas 18F-fluorocholine PET-CT exhibits excellent diagnostic performance in patients with negative 99mTc-MIBI (technetium-99m methoxyisobutylisonitrile) findings or multiglandular disease. Germline genetic testing is recommended for patients with early-onset PHPT, recurrent or multiglandular parathyroid disease, or suspected parathyroid carcinoma to guide the extent of surgical resection and avoid unnecessary bilateral neck exploration. Minimally invasive parathyroidectomy is the gold standard for solitary parathyroid adenomas. Ablation therapy is a viable option for patients who are unfit for surgery, whereas pharmacotherapy should be tailored according to whether hypercalcemia or skeletal disease is the predominant feature. ConclusionsPrecision management of PHPT requires the integration of four core pillars: biochemical characterization, molecular mechanisms, multimodal imaging, and genetic stratification. A stratified diagnostic framework coupled with a tiered clinical pathway can overcome the traditional “one-size-fits-all” empirical treatment model and establish a standardized closed-loop system of “screening–referral–follow-up”, thereby improving overall diagnostic yield and therapeutic outcomes.