Bone morphogenetic protein 10, a rising star in the field of diabetes and cardiovascular disease.

Early research suggested that bone morphogenetic protein 10 (BMP10) is primarily involved in cardiac development and congenital heart disease processes. BMP10 is a newly identified cardiac-specific protein. In recent years, reports have emphasized the effects of BMP10 on myocardial apoptosis, fibrosis and immune response, as well as its synergistic effects with BMP9 in vascular endothelium and role in endothelial dysfunction. We believe that concentrating on this aspect of the study will enhance our knowledge of the pathogenesis of diabetes and the cardiovascular field. However, there have been no reports of any reviews discussing the role of BMP10 in diabetes and cardiovascular disease. In addition, the exact pathogenesis of diabetic cardiomyopathy is not fully understood, including myocardial energy metabolism disorders, microvascular changes, abnormal apoptosis of cardiomyocytes, collagen structural changes and myocardial fibrosis, all of which cause cardiac function impairment directly or indirectly and interact with one another. This review summarizes the research results of BMP10 in cardiac development, endothelial function and cardiovascular disease in an effort to generate new ideas for future research into diabetic cardiomyopathy.

Clinical study on the efficacy of postural control combined with electroacupuncture in treating dysphagia after stroke.

Objective: To evaluate the clinical effectiveness of combining postural control with electroacupuncture in the treatment of dysphagia following stroke, with the goal of establishing a solid clinical foundation for this therapeutic approach and investigating potential mechanisms to stimulate additional research and progress in post-stroke dysphagia management. Methods: 138 patients who met the diagnostic and inclusion criteria were enrolled and divided into control group and observation group. Both groups received conventional rehabilitation training. Additionally, the control group received swallowing training and diet optimize, while the observation group received swallowing training, diet optimize, posture control as well as electroacupuncture therapy. After four weeks, swallowing function was assessed and compared between the two groups using the Standardized Swallowing Assessment (SSA) score and water swallowing test (WST). Results: Patients who underwent postural control therapy in combination with electroacupuncture demonstrated significantly higher treatment efficacy compared to the control group. Notably, The SSA score and WST score in both groups decreased significantly, and the observation group showed more improvements in aspiration compared to the control group. Conclusion: The integration of posture control, electroacupuncture, and conventional rehabilitation training can effectively lower the degree of post-stroke swallowing disorders, restore swallowing function, and significantly reduce the occurrence of complications such as aspiration, fever, and nutritional disorders. Moreover, this approach significantly improves the quality of life of patients and is more effective than conventional rehabilitation training in treating post-stroke swallowing disorders. Clinical trial registration: https://www.chictr.org.cn/, Identifier ChiCTR2300075870.

Elucidating the molecular basis of ATP-induced cell death in breast cancer: Construction of a robust prognostic model.

BACKGROUND: Breast cancer is a multifaceted and formidable disease with profound public health implications. Cell demise mechanisms play a pivotal role in breast cancer pathogenesis, with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence. AIM: To investigate the impact of ATP-induced cell death (AICD) on breast cancer, enhancing our understanding of its mechanism. METHODS: The foundational genes orchestrating AICD mechanisms were extracted from the literature, underpinning the establishment of a prognostic model. Simultaneously, a microRNA (miRNA) prognostic model was constructed that mirrored the gene-based prognostic model. Distinctions between high- and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized, with the aim of delineating common influence mechanisms, substantiated through enrichment analysis and immune infiltration assessment. RESULTS: The mRNA prognostic model in this study encompassed four specific mRNAs: P2X purinoceptor 4, pannexin 1, caspase 7, and cyclin 2. The miRNA prognostic model integrated four pivotal miRNAs: hsa-miR-615-3p, hsa-miR-519b-3p, hsa-miR-342-3p, and hsa-miR-324-3p. B cells, CD4+ T cells, CD8+ T cells, endothelial cells, and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways, while miRNA risk scores significantly enriched 29 signaling pathways, with 16 pathways being jointly enriched. CONCLUSION: Of paramount significance, distinct mRNA and miRNA signature models were devised tailored to AICD, both potentially autonomous prognostic factors. This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools, offering an unparalleled window for innovative interventions. Essentially, this paper reveals the hitherto enigmatic link between AICD and breast cancer, potentially leading to revolutionary progress in personalized oncology.

Canagliflozin combined with aerobic exercise protects against chronic heart failure in rats.

To determine the efficacy and potential protective mechanism of canagliflozin combined with aerobic exercise in treating chronic heart failure (CHF). Isoproterenol was injected into rats to create CHF models. The rats were then subsequently divided into saline, canagliflozin (3 mg/kg/d), aerobic exercise training, and canagliflozin combined with aerobic exercise training. Compared to the CHF group, the canagliflozin combined with the aerobic exercise group had superior ventricular remodeling and cardiac function. In rats treated with canagliflozin combined with aerobic exercise, the expression of cytochrome P450 (CYP) 4A3, CYP4A8, COL1A1, COL3A1, and FN1 was reduced, while the expression of CYP26B1, ALDH1A2, and CYP1A1 increased significantly. Additionally, canagliflozin combined with aerobic exercise decreased the phosphorylation of AKT and ERK1/2. Canagliflozin combined with aerobic exercise has a positive effect on the development of CHF via the regulation of retinol metabolism and the AKT/ERK signaling pathway.

Efficacy of polyethylene glycol loxenatide for type 2 diabetes mellitus patients: a systematic review and meta-analysis.

Objective: Some studies have proved that polyethylene glycol loxenatide (PEG-Loxe) has significant effects on controlling blood glucose and body weight in patients with type 2 diabetes mellitus (T2DM), but there is still some controversy over the improvement of blood lipid profiles (BLP) and blood pressure (BP), and more evidences are needed to verify such effects. Therefore, this study was conducted to provide a comprehensive evaluation of the efficacy of PEG-Loxe in improving blood glucose (BG), BLP, BP, body mass index (BMI), and body weight (BW) in patients with T2DM for clinical reference. Methods: Randomized controlled trials (RCT) in which PEG-Loxe was applied to treat T2DM were retrieved by searching PubMed, Cochrane Library, Embase, Medline, Scopus, Web of Science, China National Knowledge Infrastructure, China Scientific Journal, Wanfang Data, and SinoMed databases. Outcome measures included BG, BLP, BP, BMI, and BW. RevMan 5.3 software was used to perform data analysis. Results: Eighteen trials were identified involving 2,166 patients. In experimental group 1,260 patients received PEG-Loxe alone or with other hypoglycemic agents, while in control group 906 patients received placebo or other hypoglycemic agents. In the overall analysis, PEG-Loxe significantly reduced the levels of glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-h postprandial blood glucose (2-h PBG), BMI, and BW compared with control group. However, it had no obvious effect on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Conclusion: PEG-Loxe has better hypoglycemic effects compared with placebo in patients with T2DM, but could not significantly improved TG, LDL-C, HDL-C, SBP, and DBP. And the combination of conventional hypoglycemic drugs (CHD) and PEG-Loxe could more effectively improve the levels of HbA1c, FPG, 2-h PBG, TC, TG, BMI, and BW compared with CHD in T2DM patients. Systematic Review Registration: www.inplasy.com, identifier INPLASY202350106.

Effects of once-weekly glucagon-like peptide-1 receptor agonists on type 2 diabetes mellitus complicated with coronary artery disease: Potential role of the renin-angiotensin system.

AIM: To investigate the potential mechanism of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RA) in the treatment of type 2 diabetes mellitus (T2DM) complicated with coronary artery disease (CAD). METHODS: We searched both Chinese and English databases for randomized controlled trials related to once-weekly GLP-1 RA for T2DM complicated with CAD to verify the safety and efficacy of GLP-1 RA. The underlying mechanism was analysed by network pharmacology. RESULTS: In total, 13 studies with 35 563 participants were included in the analysis. The pooled analysis found that dulaglutide, exenatide and semaglutide outperformed placebo in cardiovascular outcomes in patients with T2DM, with a significant reduction in the incidence of non-fatal stroke (p < .00). Levels of cardiovascular risk factors were significantly reduced in the once-weekly GLP-1 RA group compared with the conventional treatment group (glycated haemoglobin: p < .00; fasting blood glucose: p < .00; weight: p < .00; systolic blood pressure: p < .00; total cholesterol: p < .00; low-density lipoprotein cholesterol: p < .00). Network pharmacology results were enriched to the renin-angiotensin system, and matrix metalloproteinase 2 and renin (REN) may be the key targets. In addition, four key targets of dulaglutide, five key targets of exenatide and two key targets of semaglutide were enriched. CONCLUSIONS: Our study suggests that once-weekly GLP-1 RA may have a potential protective effect on cardiovascular events in patients with T2DM combined with CAD, possibly through the renin-angiotensin system. However, further research is needed to confirm these findings and determine cause and effect.

Ultra-weak photon emission as a potential tool for evaluating the therapeutic effect of traditional Chinese medicine in patients with type 2 diabetes.

Background: Traditional Chinese medicine (TCM) has been used to prevent and treat type 2 diabetes (T2DM) for thousands of years. The holistic view of TCM and the "multitarget" characteristics of Chinese medicine have unique advantages in the prevention and treatment of T2DM. TCM syndrome differentiation and treatment are effective for T2DM; however, currently, the therapeutic effect of TCM is generally evaluated by asking for patients' subjective feelings, or by checking the changes in relevant indicators. The main problems are that the patient's descriptions are unclear and subjective, and although the self-reported symptoms may have improved significantly, the relevant indicators are sometimes not obvious, which cannot truly reflect the therapeutic effect of TCM. Therefore, it is urgent to develop a novel, sensitive, and noninvasive method to quantitatively evaluate the therapeutic effect of TCM. Methods: In this study, ultra-weak photon emission (UPE) was measured at four sites of hands of T2DM patients with Qi-Yin deficiency before treatment and after 1 and 2 weeks of treatment with TCM. The UPE intensity and spectral distribution were calculated and analyzed using the results measured at these four sites. Spearman's correlation coefficient was used to quantify the correlation between the UPE parameters and the syndrome scores of TCM. Results: The UPE intensity of T2DM patients with Qi-Yin deficiency decreased gradually with the course of the treatment and was significantly lower than that before the treatment. The ratio of photon counts between the wavelength ranges of 495-550 nm and 550-610 nm after the treatment was higher than that before the treatment and negatively correlated with the corresponding syndrome scores so that the degree of symptoms improvement could be characterized by the ratio (495-550 nm/550-610 nm). Conclusions: The therapeutic effect of TCM in T2DM patients with Qi-Yin deficiency can be shown at the level of UPE. UPE is a potential and noninvasive tool for evaluating the therapeutic effect of TCM in patients with T2DM.

Corrigendum: A biophoton method for identifying the quality states of fresh Chinese herbs.

[This corrects the article DOI: 10.3389/fphar.2023.1140117.].

The Efficacy of Microfracture Combined with Extracorporeal Shock Wave Therapy for Treating Osteochondral Lesion of the Talus and the Quality of Regenerated Cartilage: A Retrospective Cohort Study and MRI Assessment.

BACKGROUND: osteochondral lesion of the talus (OLT) is a common disease in the physically active population, and extracorporeal shock wave therapy (ESWT) is a noninvasive treatment. We hypothesized that microfracture (MF) combined with ESWT may have great potential to become a novel combination treatment of OLT. METHODS: the OLT patients who received MF + ESWT or MF + platelet-rich plasma (PRP) injection were retrospectively included, with a minimal follow up of 2y. The daily activating VAS, exercising VAS, and American Orthopedic Foot and Ankle Society Ankle-Hindfoot Score (AOFAS) were used to assess the efficacy and functional outcome, and ankle MRI T2 mapping was used to evaluate the quality of regenerated cartilage in the OLT patients. RESULTS: only transient synovium-stimulated complications were found during the treatment sessions; the complication rate and daily activating VAS did not have differences between groups. MF + ESWT had a higher AOFAS and a lower T2 mapping value than MF + PRP at the 2y follow up. CONCLUSIONS: the MF + ESWT had superior efficacy for treating OLT, which resulted in better ankle function and more hyaline-like regenerated cartilage, superior to the traditional MF + PRP.

Printable and Flexible Humidity Sensor Based on Graphene -Oxide-Supported MoTe2 Nanosheets for Multifunctional Applications.

This study focuses on a novel humidity sensor composed of graphene-oxide (GO)-supported MoTe2 nanosheets. Conductive Ag electrodes were formed on PET substrates by inkjet printing. A thin film of GO-MoTe2 was deposited on the Ag electrode used for adsorbing humidity. The experiment's results demonstrate that MoTe2 are attached to GO nanosheets uniformly and tightly. The capacitive output of the sensors with various ratios of GO/MoTe2 has been tested for different levels of humidity (11.3-97.3%RH) at room temperature (25 °C). As a consequence, the obtained hybrid film exhibits superior sensitivity (94.12 pF/%RH). The structural integrity and interaction of different components were discussed to afford the prominent humidity sensitivity performance. Under the bending condition, the output curve of the sensor has no obvious fluctuation. This work provides a low-cost way to build flexible humidity sensors with high-performance in environmental monitoring and healthcare.

A biophoton method for identifying the quality states of fresh Chinese herbs.

Introduction: The quality of Chinese herbs is the basis for ensuring their safety and efficacy. However, the quality evaluation system is imperfect. In particular, there is a lack of quality evaluation methods for fresh Chinese herbs during growth. The biophoton is a common phenomenon and provides complete information about the interior of the living system, which is consistent with the holistic concept of traditional Chinese medicine. Therefore, we aim to correlate the biophoton characteristics with the quality states to find the biophoton parameters that can characterize the quality states of fresh Chinese herbs. Methods: The biophoton characteristics of motherwort and safflower were measured and characterized by the counts per second (CPS) in the steady state and the initial intensity (I0) and coherent time (T) of delayed luminescence. The active ingredient content was measured by ultra-high-performance liquid chromatography (UPLC). The pigment content of motherwort leaves was measured by UV spectrophotometry. The t-test and correlation analysis were performed on the experimental results. Results: The CPS and I0 of motherwort and I0 of safflower showed a significant downward trend during the growth process, and their active ingredient content showed a trend that increased and then decreased. The CPS, I0, and the content of active ingredients and pigments in a healthy state were significantly higher than those in a poor state, while T showed the opposite results. The CPS and I0 were all significantly and positively correlated with the content of active ingredients and pigments, while the T of motherwort showed the opposite results. Conclusion: It is feasible to identify the quality states of fresh Chinese herbs by using their biophoton characteristics. Both CPS and I0 have better correlations with the quality states and can be considered characteristic parameters of the quality of fresh Chinese herbs.

Deficits in psychological resilience and problem-solving ability in adolescents with suicidal ideation.

OBJECTIVES: This study aimed to explore differences between psychological resilience and problem-solving ability in grade one junior middle school adolescents with and without suicidal ideation, focusing on the relationship between these factors and suicidal ideation. METHODS: Ninety-nine adolescents (aged 10 to 14) were divided into Suicidal Ideation (SI, n = 49) and Non-Suicidal Ideation (NSI, n = 50) grouped by the Self-rating Idea of Suicide Scale (SIOSS). The Psychological Resilience Scale (PRS) and Tower of Hanoi task (TOH) were applied to assess psychological resilience and problem-solving ability, respectively. RESULTS: The SI group scored significantly lower than the NSI group on PRS (p < 0.001) and performed more poorly on TOH than the NSI group, with more mistakes in the number of errors index (p < 0.001) and requiring a longer time in the task completion time index (p < 0.05). Among all the participants in this study, a significant negative correlation was observed between PRS and SIOSS (r = - 0.413, p < 0.01). The sub-dimensions of PRS including emotional control, family support, and interpersonal assistance were significantly negatively correlated with the SIOSS total score (r = - 0.361, - 0.360, - 0.382; p < 0.01). CONCLUSIONS: This study profiled the characteristics and differences in psychological resilience and problem-solving ability between adolescents with and without suicidal ideation. The data suggested adolescents with SI might have deficits in psychological resilience and problem-solving ability, which may serve as potential targets for suicide intervention.

Oxidative stress and DNA damage in earthworms induced by methyl tertiary-butyl ether in natural soils.

Adverse effects of methyl tertiary-butyl ether (MTBE) have been noticed at different trophic levels by international researchers. However, there was unclear evidence about its effects on oxidative stress and DNA damage in earthworms. In this study, earthworms were cultivated in various doses of MTBE (0.0 mg/kg, 10.0 mg/kg, 30.0 mg/kg, and 60.0 mg/kg) contaminated agricultural soil for 7 days, 14 days, 21 days, and 28 days, respectively. The result showed that the reactive oxygen species (ROS) content of earthworms significantly increased in MTBE treatment groups compared to the control group. In MTBE treatment groups, the activities of superoxide dismutase, catalase, peroxidase, and glutathione S-transferase were significantly activated at the exposure of 7 days, which increased by 36.3-78.9%, 51.8-97.3%, 36.5-61.9%, and 12.0-54.8%, respectively. Then, the activities of these defense enzymes showed various changes following the changes in exposure times and MTBE concentrations. Especially in the 60.0 mg kg-1 group, both antioxidant enzymes and GST were still significantly activated at the exposure of 14 days and then significantly inhibited at the exposure of 28 days. The analysis of olive tail moment showed significant DNA damage in the 10.0 mg kg-1 group at the exposure of 28 days, and this damage in 30.0 mg/kg and 60.0 mg/kg groups was found at the exposure of 7 days. This result was consistent with the malondialdehyde accumulation in earthworms. Additionally, the analysis of IBRv2 showed the effects of MTBE treatments on earthworms in dose- and time-dependent manners. This study helps better to understand the effects of MTBE on soil invertebrate animals and provide theoretical support for soil protection in governing MTBE application.

ATP-induced cell death: a novel hypothesis for osteoporosis.

ATP-induced cell death has emerged as a captivating realm of inquiry with profound ramifications in the context of osteoporosis. This study unveils a paradigm-shifting hypothesis that illuminates the prospective involvement of ATP-induced cellular demise in the etiology of osteoporosis. Initially, we explicate the morphological attributes of ATP-induced cell death and delve into the intricacies of the molecular machinery and regulatory networks governing ATP homeostasis and ATP-induced cell death. Subsequently, our focus pivots towards the multifaceted interplay between ATP-induced cellular demise and pivotal cellular protagonists, such as bone marrow-derived mesenchymal stem cells, osteoblasts, and osteoclasts, accentuating their potential contributions to secondary osteoporosis phenotypes, encompassing diabetic osteoporosis, glucocorticoid-induced osteoporosis, and postmenopausal osteoporosis. Furthermore, we probe the captivating interplay between ATP-induced cellular demise and alternative modalities of cellular demise, encompassing apoptosis, autophagy, and necroptosis. Through an all-encompassing inquiry into the intricate nexus connecting ATP-induced cellular demise and osteoporosis, our primary goal is to deepen our comprehension of the underlying mechanisms propelling this malady and establish a theoretical bedrock to underpin the development of pioneering therapeutic strategies.

Adenosine triphosphate induced cell death: Mechanisms and implications in cancer biology and therapy.

Adenosine triphosphate (ATP) induced cell death (AICD) is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions. This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology. This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer. This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis, deciphering the intricate mechanisms governing AICD, elucidating its intricate involvement in cancer signaling pathways, and scrutinizing validated key genes. Moreover, the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.

The modulation of gut microbiota by herbal medicine to alleviate diabetic kidney disease - A review.

The treatment of diabetic kidney disease (DKD) has been the key concern of the medical community. Herbal medicine has been reported to alleviate intestinal dysbiosis, promote the excretion of toxic metabolites, and reduce the secretion of uremic toxins. However, the current understanding of the modulation of the gut microbiota by herbal medicine to delay the progression of DKD is still insufficient. Consequently, we reviewed the knowledge based on peer-reviewed English-language journals regarding regulating gut microbiota by herbal medicines in DKD. It was found that herbal medicine or their natural extracts may have the following effects: modulating the composition of intestinal flora, particularly Akkermansia, Lactobacillus, and Bacteroidetes, as well as adjusting the F/B ratio; increasing the production of SCFAs and restoring the intestinal barrier; reducing the concentration of uremic toxins (p-cresol sulfate, indole sulfate, TMAO); inhibiting inflammation and oxidative stress.

Xianling Gubao attenuates high glucose-induced bone metabolism disorder in MG63 osteoblast-like cells.

Diabetes mellitus (DM) patients are prone to osteoporosis, and high glucose (HG) can affect bone metabolism. In the present study, we investigated the protective effects of traditional Chinese herbal formulation Xianling Gubao (XLGB) on HG-treated MG63 osteoblast-like cells. MG63 cells were incubated with control (mannitol), HG (20 mM glucose) or HG + XLGB (20 mM glucose+200 mg/L XLGB) mediums. Cell proliferation, apoptosis, migration and invasion were examined using CCK8, colony-formation, flow cytometry, Hoechst/PI staining, wound-healing and transwell assays, respectively. ELISA, RT-PCR and western blot analysis were used to detect the levels of osteogenesis differentiation-associated markers such as ALP, OCN, OPN, RUNX2, OPG, and OPGL in MG63 cells. The levels of the PI3K/Akt signaling pathway related proteins, cell cycle-related proteins, and mitochondrial apoptosis-related proteins were detected using western blot analysis. In HG-treated MG63 cells, XLGB significantly attenuated the suppression on the proliferation, migration and invasion of MG63 cells caused by HG. HG downregulated the activation of the PI3K/Akt signaling pathway and the expressions of cell cycle-related proteins, while XLGB reversed the inhibition of HG on MG63 cells. Moreover, XLGB significantly reduced the promotion on the apoptosis of MG63 cells induced by HG, the expressions of mitochondrial apoptosis-related proteins were suppressed by XLGB treatment. In addition, the expressions of osteogenesis differentiation-associated proteins were also rescued by XLGB in HG-treated MG63 cells. Our data suggest that XLGB rescues the MG63 osteoblasts against the effect of HG. The potential therapeutic mechanism of XLGB partially attributes to inhibiting the osteoblast apoptosis and promoting the bone formation of osteoblasts.

Bariatric surgery for diabetic comorbidities: A focus on hepatic, cardiac and renal fibrosis.

Continuously rising trends in diabetes render this disease spectrum an epidemic proportion worldwide. As the disease progresses, the pathological effects of diabetes may impair the normal function of several vital organs, eventually leading to increase the risk of other diabetic comorbidities with advanced fibrosis such as non-alcoholic fatty liver disease, diabetic cardiomyopathy, and diabetic kidney disease. Currently, lifestyle changes and drug therapies of hypoglycemic and lipid-lowering are effective in improving multi-organ function, but therapeutic efficacy is difficult to maintain due to poor compliance and drug reactions. Bariatric surgery, including sleeve gastrectomy and Roux-en-Y gastric bypass surgery, has shown better results in terms of prognosis for diabetes through long-term follow-up. Moreover, bariatric surgery has significant long-term benefits on the function of the heart, liver, kidneys, and other organs through mechanisms associated with reversal of tissue fibrosis. The aim of this review is to describe the impact of type 2 diabetes mellitus on hepatic, cardiac and renal fibrosis and to summarize the potential mechanisms by which bariatric surgery improves multiple organ function, particularly reversal of fibrosis.

Exploration of the main active components and pharmacological mechanism of Yerba Mate based on network pharmacology.

INTRODUCTION: Yerba mate is widely consumed in South American countries and is gaining popularity around the world. Long-term consumption of yerba mate has been proven to have health-care functions and therapeutic effects on many diseases; however, its underlying mechanism has not been clearly elucidated. In this research, we explored the pharmacological mechanism of yerba mate through a network pharmacological approach. MATERIAL AND METHODS: The bioactive components of yerba mate were screened from published literature and the Traditional Chinese Medicine System Pharmacology Database (TCMSP), and the targets and related diseases were retrieved by TCMSP. Furthermore, the component-target-disease network an protein-protein interaction (PPI) network were constructed, and combined with gene ontology (GO) functional analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis to explore the pharmacological mechanism of yerba mate. RESULTS: As a result, 16 bioactive components of yerba mate were identified, which acted on 229 targets in total. Yerba mate can be used to treat 305 diseases, such as breast cancer, asthma, Alzheimer's disease, osteoarthritis, diabetes mellitus, atherosclerosis, and obesity. Protein kinase B (AKT1), signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 1 (MAPK1), transcription factor AP-1 (JUN), cellular tumour antigen (p53) TP53, tumour necrosis factor (TNF), transcription factor p65 (RELA), interleukin-6 (IL6), amyloid-beta precursor protein (APP), and vascular endothelial growth factor A (VEGFA) were identified as the key targets of yerba mate playing pharmacological roles. The signalling pathways identified by KEGG pathway enrichment analysis that were most closely related to the effects of yerba mate included pathways in cancer, fluid shear stress and atherosclerosis, and human cytomegalovirus infection. CONCLUSION: the results of our study preliminarily verify the basic pharmacological action and possible mechanism of yerba mate and provide a reference for the further development of its medicinal value.

Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacology.

Aims: To evaluate the effectiveness and potential mechanism of calcium dobesilate (CaD) in diabetic kidney disease (DKD) patients. Methods: We searched for available randomized controlled studies on DKD patients' treatment with CaD through open databases. Continuous variables were expressed as standardized mean difference (SMD) with a 95% confidence interval (CI). The putative targets and possible pathways of CaD on DKD were analyzed by network pharmacology. Molecular docking was employed to verify the match between CaD and the target genes. Results: In the meta-analysis, 42 trials were included, involving 3,671 DKD patients, of which 1,839 received CaD treatment in addition to conventional treatment, while 1,832 received conventional treatment. Compared with routine therapy, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) significantly decreased in the CaD treatment (early stage of DKD, Scr: p < 0.00001; BUN: p < 0.0001; clinical stage of DKD, Scr: p < 0.00001; BUN: p < 0.00001; kidney failure stage, Scr: p = 0.001; BUN: p = 0.004). The levels of serum cystatin C (Cys-C), urine levels of molecules reflecting kidney function (urinary albumin excretion rate (UAER) and micro glycoprotein), and inflammatory factors [hypersensitive c-reactive protein (hs-CRP)] were reduced compared with control groups, while glomerular filtration rate (GFR) was increased in patients treated with CaD for 12 weeks. CaD also showed a better effect on improving endothelial function. Network pharmacology results showed that the interaction pathway between CaD and DKD was mainly enriched in MAPK and chemokine signaling pathways. AKT1, CASP3, IGF1, MAPK8, and CCL5 might be the key targets for CaD in treating DKD. Conclusion: Combination with CaD is effective and safe in patients with DKD. Inhibition of MAPK and chemokine signaling pathways might be vital in treating CaD in DKD patients.