Here we provide a systematic discussion of the underlying mechanisms of dietary fructose in contributing to the development and progression of NAFLD, and suggest the possible targets to prevent the pathogenetic process.Traditional Chinese medicine (TCM) usually plays therapeutic roles on complex diseases in the form of formulas. However, the multicomponent and multitarget characteristics of formulas bring great challenges to the mechanism analysis and secondary development of TCM in treating complex diseases. Modern bioinformatics provides a new opportunity for the optimization of TCM formulas. In this report, a new bioinformatics analysis of a computational network pharmacology model was designed, which takes Chai-Hu-Shu-Gan-San (CHSGS) treatment of depression as the case. In this model, effective intervention space was constructed to depict the core network of the intervention effect transferred from component targets to pathogenic genes based on a novel node importance calculation method. The intervention-response proteins were selected from the effective intervention space, and the core group of functional components (CGFC) was selected based on these intervention-response proteins. Results show that the enriched pathways and GO terms of intervention-response proteins in effective intervention space could cover 95.3 and 95.7% of the common pathways and GO terms that respond to the major functional therapeutic effects. Additionally, 71 components from 1,012 components were predicted as CGFC, the targets of CGFC enriched in 174 pathways which cover the 86.19% enriched pathways of pathogenic genes. Based on the CGFC, two major mechanism chains were inferred and validated. Finally, the core components in CGFC were evaluated by in vitro experiments. These results indicate that the proposed model with good accuracy in screening the CGFC and inferring potential mechanisms in the formula of TCM, which provides reference for the optimization and mechanism analysis of the formula in TCM.Pyroptosis is a recently identified type of lytic programmed cell death, in which pores form in the plasma membrane, and cells swell, rupture, and then release their contents, including inflammatory cytokines. Molecular studies indicated that pyroptosis may occur via a gasdermin D (GSDMD) and caspase-1 (Casp1) -dependent classical pathway, a GSDMD and Casp11/4/5-dependent non-classical pathway, or a gasdermin E (GSDME) and Casp3-dependent pathway. Studies of animal models and humans indicated that pyroptosis can exacerbate several complications of diabetes, including diabetic nephropathy (DN), a serious microvascular complication of diabetes. Many studies investigated the mechanism mediating the renoprotective effect of GSDMD regulation in the kidneys of patients and animal models with diabetes. As a newly discovered regulatory mechanism, GSDME and Casp3-dependent pyroptotic pathway in the progression of DN has also attracted people’s attention. Z-DEVD-FMK, an inhibitor of Casp3, ameliorates albuminuria, imprr research on the function of GDSME in DN may provide valuable insights that may help to improve treatments for this disease.Obesity and type 2 diabetes mellitus (T2DM) are preconditions for the development of metabolic syndrome, which is reaching pandemic levels worldwide, but there are still only a few anti-obesity drugs available. One of the promising tools for the treatment of obesity and related metabolic complications is anorexigenic peptides, such as prolactin-releasing peptide (PrRP). PrRP is a centrally acting neuropeptide involved in food intake and body weight (BW) regulation. In its natural form, it has limitations for peripheral administration; thus, we designed analogs of PrRP lipidized at the N-terminal region that showed high binding affinities, increased stability and central anorexigenic effects after peripheral administration. In this review, we summarize the preclinical results of our chronic studies on the pharmacological role of the two most potent palmitoylated PrRP31 analogs in various mouse and rat models of obesity, glucose intolerance, and insulin resistance. We used mice and rats with diet-induced obesity fed a high-fat diet, which is considered to simulate the most common form of human obesity, or rodent models with leptin deficiency or disrupted leptin signaling in which long-term food intake regulation by leptin is distorted. The rodent models described in this review are models of metabolic syndrome with different severities, such as obesity or morbid obesity, prediabetes or diabetes and hypertension. We found that the effects of palmitoylated PrRP31 on food intake and BW but not on glucose intolerance require intact leptin signaling. Thus, palmitoylated PrRP31 analogs have potential as therapeutics for obesity and related metabolic complications.Herbal preparations of willow bark (Salix cortex) are available in many countries as non-prescription medicines for pain and inflammation, and also as dietary supplements. Currently only little information on toxicity and drug interaction potential of the extracts is available. This study now evaluated the effects of two Salix cortex extracts on human hepatocyte-like HepaRG cells, in view of clinically relevant CYP450 enzyme activity modulation, cytotoxicity and production of reactive oxygen species (ROS). Drug metabolism via the CYP450 enzyme system is considered an important parameter for the occurrence of drug-drug interactions, which can lead to toxicity, decreased pharmacological activity, and adverse drug reactions. We evaluated two different bark extracts standardized to 10 mg/ml phenolic content. Herein, extract S6 (S. pentandra, containing 8.15 mg/ml total salicylates and 0.08 mg/ml salicin) and extract B (industrial reference, containing 5.35 mg/ml total salicylates and 2.26 mg/ml salicin) were tested. Both Salix cortex extracts showed no relevant reduction in cell viability or increase in ROS production in hepatocyte-like HepaRG cells. However, they reduced CYP1A2 and CYP3A4 enzyme activity after 48 h at ≥25 μg/ml, this was statistically significant only for S6. CYP2C19 activity inhibition (0.5 h) was also observed at ≥25 μg/ml, mRNA expression inhibition by 48 h treatment with S6 at 25 μg/ml. In conclusion, at higher concentrations, the tested Salix cortex extracts showed a drug interaction potential, but with different potency. Given the high prevalence of polypharmacy, particularly in the elderly with chronic pain, further systematic studies of Salix species of medical interest should be conducted in the future to more accurately determine the risk of potential drug interactions.DNA immune recognition regulation mediated by the cGAS-STING pathway plays an important role in immune functions. Under normal physiological conditions, cGAS can recognize and bind to invading pathogen DNA and activate the innate immune response. On the other hand, abnormal activation of cGAS or STING is closely related to autoimmune diseases. In addition, activation of STING proteins as a bridge connecting innate immunity and adaptive immunity can effectively restrain tumor growth. Therefore, targeting the cGAS-STING pathway can alleviate autoimmune symptoms and be a potential drug target for treating cancer. This article summarizes the current progress on cGAS-STING pathway modulators and lays the foundation for further investigating therapeutic development in autoimmune diseases and tumors.Bladder cancer is one of most common malignant urinary tract tumor types with high incidence worldwide. In general, transurethral resection of non-muscle-invasive bladder cancer followed by intravesical instillation of chemotherapy is the standard treatment approach to minimize recurrence and delay progression of bladder cancer. However, conventional intravesical chemotherapy lacks selectivity for tumor tissues and the concentration of drug is reduced with the excretion of urine, leading to frequent administration and heavy local irritation symptoms. While nanomedicines can overcome all the above shortcomings and adhere to the surface of bladder tumors for a long time, and continuously and efficiently release drugs to bladder cancers. The rapid advances in targeted therapy have led to significant improvements in drug efficacy and precision of targeted drug delivery to eradicate tumor cells, with reduced side-effects. This review summarizes the different available nano-systems of targeted drug delivery to bladder cancer tissues. The challenges and prospects of targeted therapy for bladder cancer are additionally discussed.Introduction Minimally invasive extracorporeal circulation (MiECC) reduced inflammatory burden, leading to best clinical outcomes in patients treated with coronary artery bypass grafting (CABG). Despite this, the patients with type 2 diabetes mellitus (T2DM) vs those without T2DM (non-T2DM) have a worse prognosis, caused by over-inflammation and modulated by sodium-glucose transporter 2 receptors. However, we evaluated the inflammatory burden and clinical outcomes in non-T2DM vs T2DM patients under sodium-glucose transporter 2 inhibitors (SGLT2-I users) vs non-SGLT2-I users at 5 years of follow-up post-CABG via MiECC. Materials and methods In a multicenter study, we screened consecutive patients with indications to receive CABG. The study endpoints were the inflammatory burden (circulating serum levels of tumor necrosis factor-alpha (TNF-α), interleukin 1 and 6 (IL-1 and IL-6), C-reactive protein (CRP), and leucocytes count) and the clinical outcomes at follow-up of 5 years in non-T2DM vs SGLT2-I users, in non-T2DM vs non-SGLT2-I users, and SGLT2-I users vs non-SGLT2-I users. Results At baseline, and at one year and 5 years of follow-up, the non-T2DM vs SGLT2-I users, non-T2DM vs non-SGLT2-I users, and SGLT2-I users vs non-SGLT2-I users had the lowest values of IL-1, IL-6, and TNF-α (p less then 0.05). At one year of follow-up, SGLT2-I users vs non-T2DM and non-SGLT2-I users vs non-T2DM users had a higher rate of all deaths, cardiac deaths, re-myocardial infarction, repeat revascularization, and stroke, and of the composite endpoint (p less then 0.05). In a multivariate Cox regression analysis, the composite endpoint was predicted by IL-1 [2.068 (1.367-3.129)], TNF-α [1.989 (1.081-2.998)], and SGLT2-I [0.504 (0.078-0.861)]. Conclusion In T2DM patients, the SGLT2-I significantly reduced the inflammatory burden and ameliorated clinical outcomes at 5 years of follow-up post-CABG via MiECC.Blood is a rich source of disease biomarkers, which include extracellular vesicles (EVs). EVs are nanometer-to micrometer-sized spherical particles that are enclosed by a phospholipid bilayer and are secreted by most cell types. EVs reflect the physiological cell of origin in terms of their molecular composition and biophysical characteristics, and they accumulate in blood even when released from remote organs or tissues, while protecting their cargo from degradation. The molecular components (e.g., proteins, miRNAs) and biophysical characteristics (e.g., size, concentration) of blood EVs have been studied as biomarkers of cancers and neurodegenerative, autoimmune, and cardiovascular diseases. However, most biomarker studies do not address the problem of contaminants in EV isolates from blood plasma, and how these might affect downstream EV analysis. Indeed, nonphysiological EVs, protein aggregates, lipoproteins and viruses share many molecular and/or biophysical characteristics with EVs, and can therefore co-isolate with EVs from blood plasma.