There is increasing evidence showing that the dynamic changes in the gut microbiota can alter brain physiology and behavior. Cognition was originally thought to be regulated only by the central nervous system. However, it is now becoming clear that many non-nervous system factors, including the gut-resident bacteria of the gastrointestinal tract, regulate and influence cognitive dysfunction as well as the process of neurodegeneration and cerebrovascular diseases. Extrinsic and intrinsic factors including dietary habits can regulate the composition of the microbiota. Microbes release metabolites and microbiota-derived molecules to further trigger host-derived cytokines and inflammation in the central nervous system, which contribute greatly to the pathogenesis of host brain disorders such as pain, depression, anxiety, autism, Alzheimer’s diseases, Parkinson’s disease, and stroke. Change of blood–brain barrier permeability, brain vascular physiology, and brain structure are among the most critical causes of the development of downstream neurological dysfunction. In this review, we will discuss the following parts: Overview of technical approaches used in gut microbiome studies Microbiota and immunity Gut microbiota and metabolites Microbiota-induced blood–brain barrier dysfunction Neuropsychiatric diseases ■ Stress and depression ■ Pain and migraine ■ Autism spectrum disorders Neurodegenerative diseases ■ Parkinson’s disease ■ Alzheimer’s disease ■ Amyotrophic lateral sclerosis ■ Multiple sclerosis Cerebrovascular disease ■ Atherosclerosis ■ Stroke ■ Arteriovenous malformation Conclusions and perspectives

Urinary protein quantification is critical for assessing the severity of chronic kidney disease (CKD). However, the current procedure for determining the severity of CKD is completed through evaluating 24-h urinary protein, which is inconvenient during follow-up. To quickly predict the severity of CKD using more easily available demographic and blood biochemical features during follow-up, we developed and compared several predictive models using statistical, machine learning and neural network approaches. The clinical and blood biochemical results from 551 patients with proteinuria were collected. Thirteen blood-derived tests and 5 demographic features were used as non-urinary clinical variables to predict the 24-h urinary protein outcome response. Nine predictive models were established and compared, including logistic regression, Elastic Net, lasso regression, ridge regression, support vector machine, random forest, XGBoost, neural network and k-nearest neighbor. The AU-ROC, sensitivity (recall), specificity, accuracy, log-loss and precision of each of the models were evaluated. The effect sizes of each variable were analysed and ranked. The linear models including Elastic Net, lasso regression, ridge regression and logistic regression showed the highest overall predictive power, with an average AUC and a precision above 0.87 and 0.8, respectively. Logistic regression ranked first, reaching an AUC of 0.873, with a sensitivity and specificity of 0.83 and 0.82, respectively. The model with the highest sensitivity was Elastic Net (0.85), while XGBoost showed the highest specificity (0.83). In the effect size analyses, we identified that ALB, Scr, TG, LDL and EGFR had important impacts on the predictability of the models, while other predictors such as CRP, HDL and SNA were less important. Blood-derived tests could be applied as non-urinary predictors during outpatient follow-up. Features in routine blood tests, including ALB, Scr, TG, LDL and EGFR levels, showed predictive ability for CKD severity. The developed online tool can facilitate the prediction of proteinuria progress during follow-up in clinical practice.

Platelets play a crucial role in cancer blood metastasis. Various cancer-related factors such as Toll-like receptors (TLRs), adenosine diphosphate (ADP) or extracellular matrix (ECM) can activate these small particles that function in hemostasis and thrombosis. Moreover, platelets induce Epithelial Mesenchymal Transition (EMT) to promote cancer progression and invasiveness. The activated platelets protect circulating tumor cells from immune surveillance and anoikis. They also mediate tumor cell arrest, extravasation and angiogenesis in distant organs through direct or indirect modulation, creating a metastatic microenvironment. This review summarizes the recent advances and progress of mechanisms in platelet activation and its interaction with cancer cells in metastasis.

Lung cancer, renowned for its fast progression and metastatic potency, is rising to become a leading cause of death globally. It has been long observed that lung cancer is particularly ept in spawning distant metastasis at its early stages, and it can readily colonize virtually any human organ. In recent years, cancer research has shed light on why lung cancer is endowed with its exceptional ability to metastasize. In this review, we will take a comprehensive look at the current research on lung cancer metastasis, including molecular pathways, anatomical features and genetic traits that make lung cancer intrinsically metastatic, as we go from lung cancer’s general metastatic potential to the particular metastasis mechanisms in multiple organs. We highly concerned about the advanced discovery and development of lung cancer metastasis, indicating the importance of lung cancer specific gene mutations, heterogeneity or biomarker discovery, and discussing potential opportunities and challenges. We will also introduce some current treatments that targets certain metastatic strategies of non-small cell lung cancer (NSCLC). Advances made in these regards could be critical to our current knowledge base of lung cancer metastasis.

The mechanism of pancreatic cancer (PA) is not fully understanded. In our last report, TRPM2 plays a promising role in pancreatic cancer. However, the mechanism of TRPM2 is still unknown in this dismal disease. This study was designed to investigate the role and mechanism of TRPM2 in pancreatic cancer. TRPM2 overexpressed and siRNA plasmid were created and transfected with pancreatic cancer cell line (BxPC-3) to construct the cell model. We employed CCK-8, Transwell, scratch wound, and nude mice tumor-bearing model to investigate the role of TRPM2 in pancreatic cancer. Besides, we collected the clinical data, tumor tissue sample (TT) and para-tumor sample (TP) from the pancreatic cancer patients treated in our hospital. We analyzed the mechanism of TRPM2 in pancreatic cancer by transcriptome analysis, western blot, and PCR. We blocked the downstream PKC/MEK pathway of TRPM2 to investigate the mechanism of TRPM2 in pancreatic cancer by CCK8, scratch wound healing, and transwell assays. Overexpressed TRPM2 could promote pancreatic cancer in proliferation, migration, and invasion ability in no matter the cell model or nude mice tumor-bearing model. TRPM2 level is highly negative correlated to the overall survival and progression-free survival time in PA patients, however, it is significantly increased in PA tissue as the tumor stage increases. The transcriptome analysis, GSEA analysis, western-blot, and PCR results indicate TRPM2 is highly correlated with PKC/MAPK pathways. The experiments of PKC/MEK inhibitors added to TRPM2 overexpressed BxPC-3 cell showed that significant inhibition of PA cells happened in CCK8, transwell, and wound-healing assay. TRPM2 may directly activate PKCα by calcium or indirectly activate PKCε and PKCδ by increased DAG in PA, which promote PA by downstream MAPK/MEK pathway activation.

For decades, cancer metastasis has been a heated topic for its high mortality. Previous research has shown that pre-metastatic niche and metastatic niche are the 2 crucial steps in cancer metastasis, assisting cancerous cells’ infiltration, survival, and colonization at target sites. More recent studies have unraveled details about the specific mechanisms related to the modification of pro-invasion environments. Here, we will review literatures on extracellular matrix (ECM) alterations, general cancer metastasis, organ specificity, pre-metastatic niche, metastatic niche, colony formation and impact on the course of metastasis. Respectively, the metastatic mechanisms like effect of hypoxia or inflammation on pre-metastatic niche construction, as well as the interaction between cancer cells and local milieu will be discussed. Based on the evidences of metastatic niches, we revisit and discussed the “Seed and Soil” hypothesis by Paget. This review will seek to provide insight into the mechanism of metastatic organ specificity which pre-metastatic niche and metastatic niche might suggest from an evolutionary aspect.