Exploring the Neural Correlates of Flow Experience with Multifaceted Tasks and a Single-Channel Prefrontal EEG Recording.

Flow experience, characterized by deep immersion and complete engagement in a task, is highly recognized for its positive psychological impacts. However, previous studies have been restricted to using a single type of task, and the exploration of its neural correlates has been limited. This study aimed to explore the neural correlates of flow experience with the employment of multifaceted flow-induction tasks. Six tasks spanning mindfulness, artistic tasks, free recall, and varying levels of Tetris complexity (easy, flow, and hard conditions) were employed to have relatively complete coverage of the known flow-induction tasks for a better induction of individualized flow experience. Twenty-eight participants were recruited to perform these six tasks with a single-channel prefrontal EEG recording. Significant positive correlations were observed between the subjective flow scores of the individual's best-flow-experience task and the EEG activities at the delta, gamma, and theta bands, peaking at latencies around 2 min after task onset. The outcomes of regression analysis yield a maximum R2 of 0.163. Our findings report the EEG correlates of flow experience in naturalistic settings and highlight the potential of portable and unobtrusive EEG technology for an objective measurement of flow experience.

Rethinking Sweetener Discovering: Multiparameter Modeling of Molecular Docking Results between the T1R2-T1R3 Receptor and Compounds with Different Tastes.

Molecular docking has been widely applied in the discovery of new sweeteners, yet the interpretation of computational results sometimes remains difficult. Here, the interaction between the T1R2-T1R3 sweet taste receptor and 66 tasting compounds, including 26 sweet, 19 bitter, and 21 sour substances was investigated by batch molecular docking processes. Statistical analysis of the docking results generated two novel methods of interpreting taste properties. Quantitative correlation between relative sweetness (RS) and docking results created a multiparameter model to predict sweetness intensity, whose correlation coefficient r = 0.74 is much higher than r = 0.17 for the linear correlation model between sweetness and binding energy. The improved correlation indicated that docking results besides binding energy contain undiscovered information about the ligand-protein interaction. Qualitative discriminant analysis of different tasting molecules generated an uncorrelated linear discriminant analysis (UDLA) model, which achieved an overall 93.1% accuracy in discriminating the taste of molecules, with specific accuracy for verifying sweet, bitter, and sour compounds reaching 88.0%, 92.1%, and 100%. These unprecedented models provide a unique perspective for interpreting computational results and may inspire future research on sweetener discovery.

Systemic immune-inflammatory biomarkers (SII, NLR, PLR and LMR) linked to non-alcoholic fatty liver disease risk.

Background: Systemic immune-inflammatory biomarkers including systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be associated with the risk and severity of various liver diseases. However, studies on their role and clinical significance in metabolic diseases, especially in nonalcoholic fatty liver disease (NAFLD), are limited and results are inconsistent. Methods: 10821 adults aged 20 years or older were enrolled in this cross-sectional study, sourced from six cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted logistic regression was employed to investigate the correlation between systemic immune-inflammatory biomarkers (SII, NLR, PLR, and LMR) and NAFLD risk. Restricted cubic spline regression models and segmented regression models were used to describe nonlinear relationships and threshold effects. Subgroup and sensitivity analyses were also conducted. Results: After adjusting for all confounding variables, there was a significant positive association observed between ln-transformed SII (OR= 1.46, 95% CI: 1.27-1.69, P <0.001), NLR (OR= 1.25, 95% CI: 1.05-1.49, P =0.015), LMR (OR= 1.39, 95% CI: 1.14-1.69, P = 0.002) with NAFLD. A nonlinear dose-response relationship with an inverted "U"-shaped threshold of 4.64 was observed between ln(PLR) and NAFLD risk. When ln(PLR) was below 4.64, each unit increase in ln(PLR) was associated with a 0.55-fold increase in the risk of NAFLD (OR= 1.55, 95% CI: 1.05-2.31, P <0.05). Conversely, when ln(PLR) exceeded 4.64, each unit increase in ln(PLR) was associated with a 0.40-fold decrease in the risk of NAFLD (OR= 0.60, 95% CI. 0.44-0.81, P <0.05). Conclusion: ln-transformed SII, NLR, and LMR were linearly associated with NAFLD risk. ln(PLR) showed an inverted "U"-shaped nonlinear dose-response relationship with the risk of NAFLD.

Network pharmacology combined with Mendelian randomization analysis to identify the key targets of renin-angiotensin-aldosterone system inhibitors in the treatment of diabetic nephropathy.

Background: Diabetic Nephropathy (DN) is one of the microvascular complications of diabetes. The potential targets of renin-angiotensin-aldosterone system (RAAS) inhibitors for the treatment of DN need to be explored. Methods: The GSE96804 and GSE1009 datasets, 729 RAAS inhibitors-related targets and 6,039 DN-related genes were derived from the public database and overlapped with the differentially expressed genes (DN vs. normal) in GSE96804 to obtain the candidate targets. Next, key targets were screened via the Mendelian randomization analysis and expression analysis. The diagnostic nomogram was constructed and assessed in GSE96804. Additionally, enrichment analysis was conducted and a 'core active ingredient-key target-disease pathway' network was established. Finally, molecular docking was performed. Results: In total, 60 candidate targets were derived, in which CTSC and PDE5A were screened as the key targets and had a causal association with DN as the protective factors (P < 0.05, OR < 1). Further, a nomogram exhibited pretty prediction efficiency. It is indicated that Benadryl hydrochloride might play a role in the DN by affecting the pathways of 'cytokine cytokine receptor interaction', etc. targeting the CTSC. Moreover, PDE5A might be involved in 'ECM receptor interaction', etc. for the effect of NSAID, captopril, chlordiazepoxide on DN. Molecular docking analysis showed a good binding ability of benadryl hydrochloride and CTSC, NSAID and PDE5A. PTGS2, ITGA4, and ANPEP are causally associated with acute kidney injury. Conclusion: CTSC and PDE5A were identified as key targets for RAAS inhibitors in the treatment of DN, which might provide some clinical significance in helping to diagnose and treat DN. Among the targets of RAAS inhibitors, PTGS2, ITGA4 and ANPEP have a causal relationship with acute kidney injury, which is worthy of further clinical research.

Jin-Gui-Shen-Qi Wan alleviates fibrosis in mouse diabetic nephropathy via MHC class II.

ETHNOPHARMACOLOGICAL RELEVANCE: Jin-Gui-Shen-Qi Wan (JGSQW) is a traditional Chinese medicine formula that has been traditionally used to alleviate urinary system ailments such as frequent urination and polyuria. Clinical studies have indicated that when combined with hypoglycaemic drugs, JGSQW exhibits a synergistic effect and can improve diabetic nephropathy (DN), yet its underlying mechanism and targets remain unclear. AIM OF THE STUDY: This study aims to investigate the therapeutic efficacy of JGSQW and its underlying mechanisms using a DN db/db mouse model. MATERIALS AND METHODS: Ultrahigh-performance liquid chromatography coupled with mass spectrometry was utilized to analyse the primary active compounds, blood levels, and pharmacokinetics of JGSQW. Additionally, the therapeutic effects of JGSQW and metformin on blood glucose levels, lipid levels, renal function, and renal pathology in diabetic nephropathy mice were investigated using a db/db mouse model. Proteomic analysis was carried out to identify the primary target of JGSQW in treating DN. The mechanism of action was verified by western blotting, immunohistochemistry, and immunofluorescence. Then, molecular docking and molecular dynamics, transfection, drug affinity responsive target stability (DARTS) assay and cell thermal migration assay (CETSA) further validated the targeted binding effect. RESULTS: JGSQW combined with metformin significantly improved the blood glucose levels, blood lipids, renal function, and renal pathology of DN mice. JGSQW mainly exerted its therapeutic effect on DN by targeting major histocompatibility complex class II (MHC class II) molecules. Immunohistochemistry results showed that JGSQW inhibited the expression of collagen I, fibronectin, and alpha smooth muscle actin (α-SMA) expression. Immunofluorescence and Western blot results showed that JGSQW inhibited the expression of H2-Ab1 and H2-Aa, which are MHC class II molecules, thereby suppressing CD4+ T-cell infiltration and improving diabetic kidney fibrosis. The binding ability of paeoniflorin to H2-Aa was predicted and verified by molecular, DARTS, and CETSA assays. Treatment with 80 µM paeoniflorin effectively alleviated high glucose-induced injury in the MPC-5 injury model. H2-Aa was overexpressed at this model concentration, and Western blotting further confirmed that paeoniflorin reduced glomerular podocyte fibrosis by regulating H2-Aa. CONCLUSIONS: JGSQW combined with metformin may have a synergistic effect to alleviates renal fibrosis in diabetic nephropathy by downregulating immune complex MHC class II molecules and attenuating the antigen presentation effect of MHC class II on CD4.

Reactions of Ethynyloxy Radical with Hydroperoxyl Radical: Bridging Theoretical Reaction Dynamics and Chemical Modeling of Combustion.

A detailed and accurate combustion reaction mechanism is crucial for understanding the nature of fuel combustion. In this work, a theoretical study of reaction HCCO+HO2 using M06-2X/6-311++G(d,p) for geometry optimization and combined methods based on spin-unrestricted CCSD(T)/CBS level of theory with basis set extrapolation from MP2/aug-cc-pVnZ (n=T and Q) for energy calculations were performed. The temperature- and pressure-dependent rate coefficients at 300-2000 K and 0.01-100 atm, suitable for combustion conditions, were derived using the Rice-Ramsberger-Kassel-Marcus/Master-Equation approach. Furthermore, temperature-dependent thermochemistry data of key species for the HCCO+HO2 system has also been studied. Finally, an updated ketene model is developed by supplementing the most recent theoretical work and the theoretical work in this paper. This updated model was tested to simulate the speciation of ketene oxidation in available experimental research. It is shown that the updated model for predicting ketene oxidation exhibits a high level of agreement with experimental data across a wide range of species profiles. An analysis was conducted to identify the crucial reactions that influence ketene ignition. This paper's research findings are essential for enhancing the combustion mechanism of ketene and other hydrocarbons and oxygenated hydrocarbon fuels.

Flexible molecularly imprinted fiber library for the metabolic analysis of bisphenol F and ecological risk evaluation.

Bisphenol F (BPF) has evoked global attentions due to its ubiquity and detrimental effects. Herein, a flexible molecularly imprinted fiber library was firstly proposed for the metabolic analysis of BPF in aquatic ecosystems. The library includes flexible single fibers and fiber arrays to precisely identify BPF and its metabolites with a wide range of polarities. Compared to commercial polyacrylate, the performance increased 11.56-570.98-fold. The adsorption capacity and the LogKow value were positively related. These arrays were used for the acquisition of environmental metabolomics data from aquatic ecosystems. In-depth data analysis showed that risk quotient was lower than 0.76, and bioaccumulation factor was lower than 2000 L/kg. Distribution concentration of BPF and its metabolites changed seasonally, and accumulation in sediment was much larger than that in surface water and hydrobionts. The risk is gradually increasing in sediment, but it does not reach high risk. The likelihood of bioaccumulation of parent compounds was greater than its metabolites. The library can be used in the metabolic diagnosis of pollutants with a broad range of polarities, providing a new method to acquire data for further ecological risk assessment, and offering a revolutionary strategy for environmental metabolomics investigation in aquatic ecosystems.

Natural products in traditional Chinese medicine: molecular mechanisms and therapeutic targets of renal fibrosis and state-of-the-art drug delivery systems.

Renal fibrosis (RF) is the end stage of several chronic kidney diseases. Its series of changes include excessive accumulation of extracellular matrix, epithelial-mesenchymal transition (EMT) of renal tubular cells, fibroblast activation, immune cell infiltration, and renal cell apoptosis. RF can eventually lead to renal dysfunction or even renal failure. A large body of evidence suggests that natural products in traditional Chinese medicine (TCM) have great potential for treating RF. In this article, we first describe the recent advances in RF treatment by several natural products and clarify their mechanisms of action. They can ameliorate the RF disease phenotype, which includes apoptosis, endoplasmic reticulum stress, and EMT, by affecting relevant signaling pathways and molecular targets, thereby delaying or reversing fibrosis. We also present the roles of nanodrug delivery systems, which have been explored to address the drawback of low oral bioavailability of natural products. This may provide new ideas for using natural products for RF treatment. Finally, we provide new insights into the clinical prospects of herbal natural products.

Establishment and Validation of the Nomogram Model and the Probability of Silent Cerebral Infarction After Ablation Atrial Fibrillation.

BACKGROUND: The objective of this study is to establish and validate a nomogram model for predicting the probability of silent cerebral infarction following ablation of atrial fibrillation. METHODS AND RESULTS: A retrospective observational study was conducted on the data of 238 patients with atrial fibrillation who underwent radiofrequency ablation in our hospital from October 2019 to December 2022. LASSO regression and multivariate logistics regression analysis were used to assess the independent risk factors for silent cerebral infarction after ablation. The AUC of the predictive model was 0.733 (95% CI, 0.649-0.816) and the internal validation (bootstrap = 1000) of the bootstrap method was 0.733 (95% CI 0.646-0.813). The Hosmer-Lemeshow test yields an insignificant p-value of X-squared = 10.212 and p-value = 0.2504, thus indicating an insignificant difference between predicted and observed values and good calibration results. The clinical impact curve (CIC) and clinical decision curve also prove that this graph is useful in the clinical setting. CONCLUSION: We developed an easy-to-use nomogram model to predict the probability of silent cerebral infarction following radiofrequency ablation of atrial fibrillation. This model can provide a valid assessment of the probability of postoperative silent cerebral infarction in patients undergoing radiofrequency ablation of atrial fibrillation.

Corrigendum: The science behind TCM and Gut microbiota interaction-their combinatorial approach holds promising therapeutic applications.

[This corrects the article DOI: 10.3389/fcimb.2022.875513.].

Jin-Gui-Shen-Qi Wan ameliorates diabetic retinopathy by inhibiting apoptosis of retinal ganglion cells through the Akt/HIF-1α pathway.

BACKGROUND: Jin-Gui-Shen-Qi Wan (JGSQ) has been used in China for thousands of years to treat various ailments, including frequent urination, blurred vision, and soreness in the waist and knees. It has traditional therapeutic advantages in improving eye diseases. AIM OF THE STUDY: Clinical studies have confirmed the therapeutic efficacy of JGSQ in improving diabetes and vision; however, its efficacy and pharmacological effects in treating diabetic retinopathy (DR) remain unclear. Therefore, the aim of this study was to investigate the specific pharmacological effects and potential mechanisms of JGSQ in improving DR through a db/db model. MATERIALS AND METHODS: db/db mice were given three different doses of orally administered JGSQ and metformin for 8 weeks, and then PAS staining of the retinal vascular network patch, transmission electron microscopy, H&E staining, and TUNEL staining were performed to determine the potential role of JGSQ in improving DR-induced neuronal cell apoptosis. Furthermore, network pharmacology analysis and molecular docking were carried out to identify the main potential targets of JGSQ, and the efficacy of JGSQ in improving DR was evaluated through western blotting and immunofluorescence staining, revealing its mechanism of action. RESULTS: According to the results from H&E, TUNEL, and PAS staining of the retinal vascular network patch and transmission electron microscopy, JGSQ does not have an advantage in improving the abnormal morphology of vascular endothelial cells, but it has a significant effect on protecting retinal ganglion cells from apoptosis. Through network pharmacology and molecular docking, AKT, GAPDH, TNF, TP53, and IL-6 were identified as the main core targets of JGSQ. Subsequently, through western blot and immunofluorescence staining, it was found that JGSQ can inhibit HIF-1α, promote p-AKT expression, and inhibit TP53 expression. At the same time, inhibiting the release of inflammatory factors protects retinal ganglion cells and improves apoptosis in DR. CONCLUSION: These results indicated that in the db/db DR mouse model, JGSQ can inhibit the expression of inflammatory cytokines and protect retinal ganglion cells from apoptosis, possibly by modulating the Akt/HIF-1α pathway.

Purine and purinergic receptors in health and disease.

Purines and purinergic receptors are widely distributed throughout the human body. Purine molecules within cells play crucial roles in regulating energy metabolism and other cellular processes, while extracellular purines transmit signals through specific purinergic receptors. The ubiquitous purinergic signaling maintains normal neural excitability, digestion and absorption, respiratory movement, and other complex physiological activities, and participates in cell proliferation, differentiation, migration, and death. Pathological dysregulation of purinergic signaling can result in the development of various diseases, including neurodegeneration, inflammatory reactions, and malignant tumors. The dysregulation or dysfunction of purines and purinergic receptors has been demonstrated to be closely associated with tumor progression. Compared with other subtypes of purinergic receptors, the P2X7 receptor (P2X7R) exhibits distinct characteristics (i.e., a low affinity for ATP, dual functionality upon activation, the mediation of ion channels, and nonselective pores formation) and is considered a promising target for antitumor therapy, particularly in patients with poor response to immunotherapy This review summarizes the physiological and pathological significance of purinergic signaling and purinergic receptors, analyzes their complex relationship with tumors, and proposes potential antitumor immunotherapy strategies from tumor P2X7R inhibition, tumor P2X7R overactivation, and host P2X7R activation. This review provides a reference for clinical immunotherapy and mechanism investigation.

Tanshinone I attenuates gastric precancerous lesions by inhibiting epithelial mesenchymal transition through the p38/STAT3 pathway.

BACKGROUND: Gastric precancerous lesions (GPLs) are omens for gastric cancer (GC), which developing with a series of pathological changes of gastric mucosa. Reversing epithelial-mesenchymal transition (EMT) in gastric mucosa is the main approach to restrain GPLs from evolving into cancer. Tanshinone I (Tan-I), the active ingredients of traditional Chinese herb Salvia miltiorrhiza, has exhibited anticancer effect. PURPOSE: To investigate the effect and mechanism of Tan-I in intervening GPLs, and provide a new therapeutic strategy for prevention of GC. METHODS: Gastric mucosal epithelial cells were treated with the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) to construct MNNG-induced cell (MC cell) of gastric mucosa that undergoing EMT process. Then, this study explored the effect and mechanism of Tan-I in vitro. Subsequently, this study constructed GPL mice to clarify the exact efficacy and mechanism of Tan-I on GPLs. RESULTS: Tan-I inhibited MC cell proliferation, invasion and migration. Simultaneously, the aberrant expression of E-cadherin and N-cadherin were reversed. Tan-I attenuated inflammation by reducing the release of nitric oxide, TNFα and IL-1ß. Tan-I reversed the EMT and inflammatory processes by regulating p38 and STAT3. CONCLUSION: This study showed that Tan-I inhibited the progression of GPLs by reversing the EMT process and reducing inflammation by restraining the p38/STAT3 signaling pathway.

Targeting extracellular matrix through phytochemicals: a promising approach of multi-step actions on the treatment and prevention of cancer.

Extracellular matrix (ECM) plays a pivotal and dynamic role in the construction of tumor microenvironment (TME), becoming the focus in cancer research and treatment. Multiple cell signaling in ECM remodeling contribute to uncontrolled proliferation, metastasis, immune evasion and drug resistance of cancer. Targeting trilogy of ECM remodeling could be a new strategy during the early-, middle-, advanced-stages of cancer and overcoming drug resistance. Currently nearly 60% of the alternative anticancer drugs are derived from natural products or active ingredients or structural analogs isolated from plants. According to the characteristics of ECM, this manuscript proposes three phases of whole-process management of cancer, including prevention of cancer development in the early stage of cancer (Phase I); prevent the metastasis of tumor in the middle stage of cancer (Phase II); provide a novel method in the use of immunotherapy for advanced cancer (Phase III), and present novel insights on the contribution of natural products use as innovative strategies to exert anticancer effects by targeting components in ECM. Herein, we focus on trilogy of ECM remodeling and the interaction among ECM, cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), and sort out the intervention effects of natural products on the ECM and related targets in the tumor progression, provide a reference for the development of new drugs against tumor metastasis and recurrence.

Chelerythrine chloride inhibits the progression of colorectal cancer by targeting cancer-associated fibroblasts through intervention with WNT10B/ß-catenin and TGFß2/Smad2/3 axis.

Chelerythrine chloride (CHE) is a benzodiazepine alkaloid derived from natural herbs with significant anti-tumor and anti-inflammatory activities. However, the exact role and underlying mechanisms of CHE in colorectal cancer (CRC) remain unclear. Therefore, this study is aimed to investigate the influence of CHE on the progression of CRC. Cell Counting Kit-8 assay (CCK-8), transwell, apoptosis rate, cell cycle distribution, reactive oxygen species (ROS), and colony formation determined the anti-proliferative activity of CHE in CRC cell lines. Transcriptome sequencing and western blot were used to explore the mechanism. Finally, H&E staining, Ki67, TUNEL, and immunofluorescence were conducted to verify the anti-CRC activity and potential mechanisms of CHE in vivo. CHE had a prominent inhibitory effect on the proliferation of CRC cells. CHE induces G1 and S phase arrest and induces cell apoptosis by ROS accumulation. Cancer-associated fibroblasts (CAFs) play a key role in CRC metastasis. Then, this study found that CHE regulates WNT10B/ß-catenin and TGFß2/Smad2/3 axis, thereby decreasing the expression of α-SMA, which is a maker of CAFs. Taken together, CHE is a candidate drug and a potent compound for metastatic CRC, which can intervene CAFs in a dual pathway to effectively inhibit the invasion and migration of cancer cells, which can provide a new choice for future clinical treatment.

Development and Validation of a Nomogram Model Affecting the ACT Targeting Rate During Radiofrequency Ablation of Atrial Fibrillation in China.

CONTEXT: A nomogram model affecting the activated clotting time (ACT) targeting rate during radiofrequency ablation of atrial fibrillation (RFCA) in China. PURPOSE: The aim of this study is to develop and validate a nomogram model for predicting the activated clotting time targeting rate after the initial bolus heparin dosages during the radiofrequency catheter ablation of atrial fibrillation in China. METHODS AND RESULTS: A retrospective observational study was conducted on the data of 465 patients with atrial fibrillation who underwent radiofrequency catheter ablation (RFCA) from October 2019 to June 2022. All patients were randomized into a training cohort (70%; n = 325) and a validation cohort (30%; n = 140). Independent risk factors were identified using univariate and multifactorial logistic regression analysis. The predictive nomogram model was established using R software. The nomogram was developed and evaluated based on differentiation, calibration, and clinical efficacy using concordance statistic (C-statistic), calibration plots, and decision curve analysis (DCA), respectively. The nomogram was established using three variables, including sex (OR 1.01, 95% CI 0.29-1.76, P = 0.007), heparin dose (OR 0.04; 95%CI 0.02-0.05, P < 0.001), and the baseline ACT (OR 0.03; 95%CI 0.02-0.04, P < 0.001). The C-statistic of the nomogram was 0.736 (95%CI 0.675-0.732) in the training cohort and 0.700 (95%CI 0.622-0.721) in the validation cohort. The calibration plots showed good agreement between the predictions and observations in the training and validation cohorts. The clinical decision curve also proves that the map is useful in clinical settings. CONCLUSION: The nomogram model has good discrimination and accuracy, which can screen attainment groups intuitively and individually, and has a certain predictive value for the probability of ACT reaching the target after the adequate dosage of initial heparin in Chinese patients with atrial fibrillation.

Translation Animal Models of Diabetic Kidney Disease: Biochemical and Histological Phenotypes, Advantages and Limitations.

Animal models play a crucial role in studying the pathogenesis of diseases, developing new drugs, identifying disease risk markers, and improving means of prevention and treatment. However, modeling diabetic kidney disease (DKD) has posed a challenge for scientists. Although numerous models have been successfully developed, none of them can encompass all the key characteristics of human DKD. It is essential to choose the appropriate model according to the research needs, as different models develop different phenotypes and have their limitations. This paper provides a comprehensive overview of biochemical and histological phenotypes, modeling mechanisms, advantages and limitations of DKD animal models, in order to update relevant model information and provide insights and references for generating or selecting the appropriate animal models to fit different experimental needs.

Radical oxygen species: an important breakthrough point for botanical drugs to regulate oxidative stress and treat the disorder of glycolipid metabolism.

Background: The incidence of glycolipid metabolic diseases is extremely high worldwide, which greatly hinders people's life expectancy and patients' quality of life. Oxidative stress (OS) aggravates the development of diseases in glycolipid metabolism. Radical oxygen species (ROS) is a key factor in the signal transduction of OS, which can regulate cell apoptosis and contribute to inflammation. Currently, chemotherapies are the main method to treat disorders of glycolipid metabolism, but this can lead to drug resistance and damage to normal organs. Botanical drugs are an important source of new drugs. They are widely found in nature with availability, high practicality, and low cost. There is increasing evidence that herbal medicine has definite therapeutic effects on glycolipid metabolic diseases. Objective: This study aims to provide a valuable method for the treatment of glycolipid metabolic diseases with botanical drugs from the perspective of ROS regulation by botanical drugs and to further promote the development of effective drugs for the clinical treatment of glycolipid metabolic diseases. Methods: Using herb*, plant medicine, Chinese herbal medicine, phytochemicals, natural medicine, phytomedicine, plant extract, botanical drug, ROS, oxygen free radicals, oxygen radical, oxidizing agent, glucose and lipid metabolism, saccharometabolism, glycometabolism, lipid metabolism, blood glucose, lipoprotein, triglyceride, fatty liver, atherosclerosis, obesity, diabetes, dysglycemia, NAFLD, and DM as keywords or subject terms, relevant literature was retrieved from Web of Science and PubMed databases from 2013 to 2022 and was summarized. Results: Botanical drugs can regulate ROS by regulating mitochondrial function, endoplasmic reticulum, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT), erythroid 2-related factor 2 (Nrf-2), nuclear factor κB (NF-κB), and other signaling pathways to improve OS and treat glucolipid metabolic diseases. Conclusion: The regulation of ROS by botanical drugs is multi-mechanism and multifaceted. Both cell studies and animal experiments have demonstrated the effectiveness of botanical drugs in the treatment of glycolipid metabolic diseases by regulating ROS. However, studies on safety need to be further improved, and more studies are needed to support the clinical application of botanical drugs.

Bujing Yishi tablets alleviate photoreceptor cells death via the P2X7R/CX3CL1/CX3CR1 pathway in Retinitis Pigmentosa rats.

BACKGROUND: Retinitis pigmentosa (RP) refers to a group of progressive photoreceptor degenerative diseases. The activation of microglia has been reported to play an important role in the photoreceptor degeneration in RP retinal. Bujing Yishi tablets (BJYS), a Chinese herbal medicine, has been used to treat retinal diseases in China with desirable effect in improving visual function. However, the mechanisms underlying the efficacy of BJYS treatment in RP are not yet fully understood. PURPOSE: Based on the preliminary experiments, this study aimed to investigate the therapeutic mechanism involved in treating N-Methyl-N-Nitrosourea (MNU)-induced retinal degeneration of RP with BJYS. METHODS: To explore the efficacy of BJYS, a rat experimental RP model was established through intraperitoneal injection of MNU (50 mg/kg). Two experiment was carried out. After the treatment, we conducted H&E, TUNEL, retinal cytokine levels and IBA-1 expression in microglia to confirm the impact on RP model. The specific mechanism of action of BJYS tablet was assessed by western blot, real-time polymerase chain reaction (RT-PCR), and immunofluorescence to determine the mRNA and protein expression levels involved in clarifying the effectiveness of BJYS exerted through P2X7R/CX3CL1/CX3CR1 pathway. RESULTS: Significant alleviation of retinal morphological structure and photoreceptor degeneration by BJYS treatment was observed in the retinal of MNU-induced RP rats, BJYS prevented the reduction of ONL thickness and decreased the level of apoptotic cells in ONL. It also inhibited microglia overactivation and reduced retinal levels of IL-1ß, IL-6, TNF-α. In addition, BJYS decreased the protein expression and mRNA expression of P2X7, CX3CL1 and CX3CR1 and reduced the phosphorylation of p38 MAPK. CONCLUSION: In summary, this study suggested that BJYS treatment could alleviate photoreceptors degeneration of RP by inhibiting microglia overactivation and inflammation through the P2X7R/CX3CL1/CX3CR1 pathway. These effects suggest that BJYS tablets may serve as a promising oral therapeutic agent for RP.

Renoprotective Effects of Tanshinone IIA: A Literature Review.

The kidney is an important organ in the human body, with functions such as urine production, the excretion of metabolic waste, the regulation of water, electrolyte and acid-base balance and endocrine release. The morbidity and mortality of kidney diseases are increasing year by year worldwide, and they have become a serious public health problem. In recent years, natural products derived from fungi, plants and animals have become an important alternative source of treatment for kidney diseases because of their multiple pathways, multiple targets, safety, low toxicity and few side effects. Tanshinone IIA (Tan IIA) is a lipid-soluble diterpene quinone isolated from the Chinese herb Salvia miltiorrhiza, considered as a common drug for the treatment of cardiovascular diseases. As researchers around the world continue to explore its unknown biological activities, it has also been found to have a wide range of biological effects, such as anti-cancer, anti-oxidative stress, anti-inflammatory, anti-fibrotic, and hepatoprotective effects, among others. In recent years, many studies have elaborated on its renoprotective effects in various renal diseases, including diabetic nephropathy (DN), renal fibrosis (RF), uric acid nephropathy (UAN), renal cell carcinoma (RCC) and drug-induced kidney injury caused by cisplatin, vancomycin and acetaminophen (APAP). These effects imply that Tan IIA may be a promising drug to use against renal diseases. This article provides a comprehensive review of the pharmacological mechanisms of Tan IIA in the treatment of various renal diseases, and it provides some references for further research and clinical application of Tan IIA in renal diseases.