Investigation the mechanism of iron overload-induced colonic inflammation following ferric citrate exposure.

Iron overload occurs due to excessive iron intake compared to the body's demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear. The current study aims to investigate the mechanism by which iron overload induced by FC exposure leads to colonic inflammation. To accomplish this, mice were orally exposed to three different concentrations of FC (71 mg/kg/bw (L), 143 mg/kg/bw (M) and 286 mg/kg/bw (H)) for continuous 16 weeks, with the control group receiving ultrapure water (C). Exposure to FC caused disturbances in the excretory system, altered colonic flora alpha diversity, and enriched pathogenic bacteria, such as Mucispirillum, Helicobacter, Desulfovibrio, and Shigella. These changes led to structural disorders of the colonic flora and an inflammatory response phenotype characterized by inflammatory cells infiltration, atrophy of intestinal glands, and irregular thickening of the intestinal wall. Mechanistic studies revealed that FC-exposure activated the NF-κB signaling pathway by up-regulating TLR4, MyD88, and NF-κB mRNA levels and protein expression. This activation resulted in increased production of pro-inflammatory cytokines, further contributing to the colonic inflammation. Additionally, in vitro experiments in SW480 cells confirmed the activation of NF-κB signaling pathway by FC exposure, consistent with the in vivo findings. The significance of this study lies in its elucidation of the mechanism by which iron overload caused by FC exposure leads to colonic inflammation. By identifying the role of pathogenic bacteria and the NF-κB signaling pathway, this study could potentially offer a crucial theoretical foundation for the research on iron overload, as well as provide valuable insights for clinical iron supplementation.

Dietary selenomethionine reduced oxidative stress by resisting METTL3-mediated m6A methylation level of Nrf2 to ameliorate LPS-induced liver necroptosis in laying hens.

Selenomethionine (SeMet) as the main form of daily dietary selenium, occupies essential roles in providing antioxidant and anti-inflammatory properties, which alleviates inflammatory liver damage. N6-methyladenosine (m6A) is one of the most prevalent and abundant internal transcriptional modifications that regulate gene expression. To investigate the protective mechanism of SeMet on liver injury and the regulatory effect of m6A methylation modification, we established the model by supplementing dietary SeMet, and LPS as stimulus in laying hens. LMH cells were intervened with SeMet (0.075 µM) and/or LPS (60 µg/mL). Subsequently, histopathology and ultrastructure of liver were observed. Western Blot, qRT-PCR, colorimetry, MeRIP-qPCR, fluorescent probe staining and AO/EB were used to detect total m6A methylation level, m6A methylation level of Nrf2, ROS, inflammatory and necroptosis factors. Studies showed that SeMet suppressed LPS-induced upregulation of total m6A methylation levels and METTL3 expression. Interestingly, SeMet reduced the m6A methylation level of Nrf2, activated antioxidant pathways and alleviated oxidative stress. LMH cells were transfected with 50 µm siMETTL3. SeMet/SiMETTL3 reversed the LPS-induced reduction in Nrf2 mRNA stability, slowed down its degradation rate. Moreover, LPS induced oxidative stress, led to necroptosis and activated NF-κB to promote the expression of inflammatory factors. SeMet/SiMETTL3 alleviated LPS-induced necroptosis and inflammation. Altogether, SeMet enhanced antioxidant and anti-inflammatory capacity by reducing METTL3-mediated m6A methylation levels of Nrf2, ultimately alleviating liver damage. Our findings provided new insights and therapeutic target for the practical application of dietary SeMet in the treatment and prevention of liver inflammation, and supplied a reference for comparative medicine.

[Analysis on the Current Situation of Phytoplankton in the Typical River-Lake Ecotone of Lake Poyang].

The typical river-lake ecotone (tail end area) of Poyang Lake, which is a sensitive area and prone to outbreaks of cyanobacteria bloom, is vulnerable to frequent human activities. To explore the diversity of phytoplankton community structure and the relevant driving mechanism in the typical river lake junction area of Poyang Lake, the water quality and phytoplankton at seven sampling points in the typical river lake junction area of Poyang Lake, at six sampling points in the middle section of Poyang Lake River, and at one sampling point in the main lake area were investigated in the field from 2019 to 2020 (dry season), April (flood season), July (wet season), and October (recession period). The results showed that there were seven phyla and 64 genera of phytoplankton in the typical river-lake ecotone of Poyang Lake, and the biomass and relative abundance of phytoplankton were dominated by diatoms and cyanobacteria. The biomass and abundance in the east of the typical river-lake ecotone of Poyang Lake were generally higher than those in the west, and the biomass and abundance in the river-lake ecotone were higher than those in the middle of the river. The dominant degree of cyanobacteria in the lake area and the river-lake ecotone was large, and the dominant degree of diatoms in the middle section of the river was large. The Monte Carlo test results showed that total nitrogen (TN), total phosphorus (TP), orthophosphate phosphorus (PO43--P), water depth (WD), water temperature (WT), and transparency (SD) were significantly related environmental factors affecting the distribution of the phytoplankton community. Redundancy analysis results showed that the typical river-lake ecotone in the west of Poyang Lake was highly affected by the hydration factors (TN, TP, and PO43--P), and the hydrological factors (WT, WD, and SD) in the typical river-lake ecotone in the east were highly significant. The impact factors of phytoplankton in the typical river-lake ecotone of Poyang Lake were seasonal, being greatly affected by hydration factors in winter and hydrological factors in summer.

[Mechanism of action and exogenous supplementation of vitamin D in Crohn's disease]. / ç»´ç”Ÿç´ Dåœ¨å ‹ç½—æ©ç— ä¸­çš„ä½œç”¨æœºåˆ¶åŠå¤–æºæ€§è¡¥å 作用.

Vitamin D can not only regulate calcium and phosphorus metabolism, but also exert an immunoregulatory effect. Vitamin D deficiency is common in patients with Crohn's disease (CD). Studies have shown that vitamin D is associated with CD and other autoimmune diseases and can improve the condition of patients with CD and promote their recovery by regulating intestinal immunity, repairing the intestinal mucosal barrier, inhibiting intestinal fibrosis, enhancing the response to infliximab, and regulating intestinal microbiota. Exogenous vitamin D supplementation can induce disease remission while increasing the serum level of vitamin D. However, only a few randomized, double-blind, and placebo-controlled trials have investigated the therapeutic effect of vitamin D in CD, and the optimal form of vitamin D supplementation, the specific dosage of vitamin D supplementation, and the optimal serum maintenance concentration of vitamin D remain to be clarified. This article mainly discusses the mechanism of action of vitamin D in CD and the beneficial effect of exogenous vitamin D supplementation on CD.

Mume Fructus (Prunus mume Sieb. et Zucc.) extract accelerates colonic mucosal healing of mice with colitis induced by dextran sulfate sodium through potentiation of cPLA2-mediated lysophosphatidylcholine synthesis.

BACKGROUND: Mume Fructus (MF) is the fruit of Prunus mume Sieb. et Zucc, a plant of Rosaceae family. Previous studies demonstrated that MF was capable of ameliorating ulcerative colitis (UC) in mice, its action mechanism needs to be clarified. PURPOSE: This study deciphered whether and how MF extract accelerates colonic mucosal healing, the therapeutic endpoint of UC. METHODS: Biochemical, histopathological and qRT-PCR analyses were utilized to define the therapeutic efficacy of MF on dextran sulfate sodium (DSS)-induced colitis in mice. UHPLC-QTOF-MS/MS-based metabolomics technique was adopted to explore the changes of endogenous metabolites associated with UC and responses to MF intervention. qRT-PCR analysis was performed to confirm the molecular pathway in vivo. The effects of MF and lysophosphatidylcholine (LPC) on cell viability, wound healing, proliferation, and migration were examined through a series of in vitro experiments. Moreover, the effects of different subtypes of phospholipase A2 (PLA2) inhibitors on MF-treated colonic epithelial cells were detected by wound healing test and transwell assay. RESULTS: Orally administered MF could alleviate colitis in mice mainly by accelerating the healing of colonic mucosa. Guided by an unbiased metabolomics screen, we identified LPC synthesis as a major modifying pathway in colitis mice after MF treatment. Notably, MF facilitated the synthesis of LPC by enhancing the expression of PLA2 in colitis mice. Mechanistically, MF and LPC accelerated wound closure by promoting cell migration. Moreover, the promotion of MF on wound healing and migration of colonic epithelial cells was blunted by a cytosolic phospholipase A2 (cPLA2) inhibitor. CONCLUSION: MF can facilitate colonic mucosal healing of mice with colitis through cPLA2-mediated intestinal LPC synthesis, which may become a novel therapeutic agent of UC.

Microfluidic Formulation of Curcumin-Loaded Multiresponsive Gelatin Nanoparticles for Anticancer Therapy.

Current anticancer research shows that a combination of multiple treatment methods can greatly improve the killing of tumor cells. Using the latest microfluidic swirl mixer technology, combined with chemotherapy and photothermal-ablation therapy, we developed multiresponsive targeted antitumor nanoparticles (NPs) made of folate-functionalized gelatin NPs under 200 nm in size and with encapsulated CuS NPs, Fe3O4 NPs, and curcumin (Cur). By exploring gelatin's structure, adjusting its concentration and pH, and fine-tuning the fluid dynamics in the microfluidic device, the best preparation conditions were obtained for gelatin NPs with an average particle size of 90 ± 7 nm. The comparative targeting of the drug delivery system (DDS) was demonstrated on lung adenocarcinoma A549 cells (low level of folate receptors) and breast adenocarcinoma MCF-7 cells (high level of folate receptors). Folic acid helps achieve targeting and accurate delivery of NPs to the MCF-7 tumor cells. The synergistic photothermal ablation and curcumin's anticancer activity are achieved through infrared light irradiation (980 nm), while Fe3O4 is guided with an external magnetic field to target gelatin NPs and accelerate the uptake of drugs, thus efficiently killing tumor cells. The method described in this work is simple, easy to repeat, and has great potential to be scaled up for industrial production and subsequent clinical use.

3, 3'-diindolylmethane enhances macrophage efferocytosis and subsequently relieves visceral pain via the AhR/Nrf2/Arg-1-mediated arginine metabolism pathway.

BACKGROUND: 3, 3'-diindolylmethane (DIM), a classical aryl hydrocarbon receptor (AhR) agonist, has been shown to relieve neuropathic pain, but few studies have reported the efficacy of DIM in visceral pain under colitis condition. PURPOSE: This study aimed to investigate the effect and mechanism of DIM on visceral pain under colitis condition. METHODS: Cytotoxicity was performed using the MTT assay. RT-qPCR and ELISA assays were applied to determine the expression and release of algogenic substance P (SP), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Flow cytometry was used to examine the apoptosis and efferocytosis. The expression of Arg-1-arginine metabolism-related enzymes was detected using western blotting assays. ChIP assays were used to examine the binding of Nrf2 to Arg-1. Mouse models of dextran sulfate sodium (DSS) were established to illustrate the effect of DIM and validate the mechanism in vivo. RESULTS: DIM did not directly affect expressions and release of algogenic SP, NGF and BDNF in enteric glial cells (EGCs). However, when co-cultured with DIM-pre-treated RAW264.7 cells, the release of SP and NGF was decreased in lipopolysaccharides-stimulated EGCs. Furthermore, DIM increased the number of PKH67+ F4/80+ cells in the co-culture system of EGCs and RAW264.7 cells in vitro and alleviated visceral pain under colitis condition by regulating levels of SP and NGF as well as values of electromyogram (EMG), abdominal withdrawal reflex (AWR) and tail-flick latency (TFL) in vivo, which was significantly inhibited by efferocytosis inhibitor. Subsequently, DIM was found to down-regulate levels of intracellular arginine, up-regulate levels of ornithine, putrescine and Arg-1 but not extracellular arginine or other metabolic enzymes, and polyamine scavengers reversed the effect of DIM on efferocytosis and release of SP and NGF. Moving forward, Nrf2 transcription and the binding of Nrf2 to Arg-1-0.7 kb was enhanced by DIM, AhR antagonist CH223191 abolished the promotion of DIM on Arg-1 and efferocytosis. Finally, nor-NOHA validated the importance of Arg-1-dependent arginine metabolism in DIM-alleviated visceral pain. CONCLUSION: DIM enhances macrophage efferocytosis in an arginine metabolism-dependent manner via "AhR-Nrf2/Arg-1" signals and inhibits the release of SP and NGF to relieve visceral pain under colitis condition. These findings provide a potential therapeutic strategy for the treatment of visceral pain in patients with colitis.

Self-Assembly of Selenium-Doped Carbon Quantum Dots as Antioxidants for Hepatic Ischemia-Reperfusion Injury Management.

Hepatic ischemia-reperfusion injury (HIRI) is a critical complication after liver surgery that negatively affects surgical outcomes of patients with the end-stage liver-related disease. Reactive oxygen species (ROS) are responsible for the development of ischemia-reperfusion injury and eventually lead to hepatic dysfunction. Selenium-doped carbon quantum dots (Se-CQDs) with an excellent redox-responsive property can effectively scavenge ROS and protect cells from oxidation. However, the accumulation of Se-CQDs in the liver is extremely low. To address this concern, the fabrication of Se-CQDs-lecithin nanoparticles (Se-LEC NPs) is developed through self-assembly mainly driven by the noncovalent interactions. Lecithin acting as the self-assembly building block also makes a pivotal contribution to the therapeutic performance of Se-LEC NPs due to its capability to react with ROS. The fabricated Se-LEC NPs largely accumulate in the liver, effectively scavenge ROS and inhibit the release of inflammatory cytokines, thus exerting beneficial therapeutic efficacy on HIRI. This work may open a new avenue for the design of self-assembled Se-CQDs NPs for the treatment of HIRI and other ROS-related diseases.

Prognostic value and adverse events of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in primary advanced and platinum-sensitive recurrent epithelial ovarian cancer: a systematic review and meta-analysis.

BACKGROUND: The original meta-analysis of hyperthermic intraperitoneal chemotherapy (HIPEC) is already outdated, owing to the latest trial results. This study aimed to clarify the efficacy and adverse events of cytoreductive surgery with HIPEC compared to conventional therapy for advanced and platinum-sensitive recurrent epithelial ovarian cancer (OC). METHODS: In this meta-analysis, phase II/III controlled trials regarding 'HIPEC' and 'ovarian cancer' were searched for in electronic databases from inception to March 2022. RESULTS: Twenty-one studies were included in the quantitative synthesis. The pooled hazard ratio [HR] in the HIPEC group for progression-free survival (PFS) (HR = 0.61, 95% confidence interval [CI]: 0.45-0.83, p = .002) and overall survival (OS) (HR = 0.65, 95% CI: 0.51-0.82, p < .001) were improved in the HIPEC group compared with the non-HIPEC group. For primary advanced disease, OS and PFS were significantly increased in patients receiving interval debulking surgery + HIPEC, whereas PFS was not significantly different between primary debulking surgery (PDS) + HIPEC and PDS alone. For platinum-sensitive recurrent disease, no correlation was observed for PFS and OS between the HIPEC and non-HIPEC groups (p < .05). The incidence of procedure-related complications was higher in the HIPEC group than in the non-HIPEC group (odds ratio = 1.93, 95% CI: 1.24-3.01, p < .01). The morbidity of leukopenia, neutropenia, nausea, hypoalbuminemia, and grades III-IV electrolyte disturbance was higher in the HIPEC group than in the non-HIPEC group. However, HIPEC administration reduced the risk of intra-abdominal bleeding and constipation. CONCLUSION: HIPEC-based regimens improved the clinical prognosis for primary advanced OC, whereas no significant value was elicited for recurrent OC.

Ferric citrate-induced colonic mucosal damage associated with oxidative stress, inflammation responses, apoptosis, and the changes of gut microbial composition.

Ferric citrate (FC) has been used as an iron fortifier and nutritional supplement, which is reported to induce colitis in rats, however the underlying mechanism remains to be elucidated. We performed a 16-week study of FC in male healthy C57BL/6 mice (nine-month-old) with oral administration of Ctr (0.9 % NaCl), 1.25 % FC (71 mg/kg/bw), 2.5 % FC (143 mg/kg/bw) and 5 % FC (286 mg/kg/bw). FC-exposure resulted in colon iron accumulation, histological alteration and reduce antioxidant enzyme activities, such as glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC), together with enhanced lipid peroxidation level, including malondialdehyde (MDA) level and 4-Hydroxynonenal (4-HNE) protein expression. Exposure to FC was associated with upregulated levels of the interleukin (IL)- 6, IL-1ß, IL-18, IL-8 and tumor necrosis factor α (TNF-α), while down-regulated levels of IL-4 and IL-10. Exposure to FC was positively associated with the mRNA and protein expressions of cysteine-aspartic proteases (Caspase)- 9, Caspase-3, Bcl-2-associated X protein (Bax), while negatively associated with B-cell lymphoma 2 (Bcl2) in mitochondrial apoptosis signaling pathway. FC-exposure changed the diversity and composition of gut microbes. Additionally, the serum lipopolysaccharide (LPS) contents increased in FC-exposed groups when compared with the control group, while the expression of colonic tight junction proteins (TJPs), such as Claudin-1 and Occludin were decreased. These findings indicate that the colonic mucosal injury induced by FC-exposure are associated with oxidative stress generation, inflammation response and cell apoptosis, as well as the changes in gut microbes diversity and composition.

MiR-129-3p regulates ferroptosis in the liver of Selenium-deficient broilers by targeting SLC7A11.

Selenium (Se) has been proven to be an essential trace element for organism. Se deficiency in poultry can cause widespread damage, such as exudative diathesis. The liver is not only the main organ of metabolism, but also one of the organs with high Se content in organism. Recent studies have shown that solute carrier family 7 member 11 (SLC7A11) plays a key role in the negative regulation of ferroptosis. In order to explore the mechanism of Se deficiency induces liver ferroptosis in broilers, and the role of microRNAs (miRNAs) in this process, we divided broilers into 2 groups: control group (0.2 mg/kg Se) and Se deficiency group (0.03 mg/kg Se). Hematoxylin-Eosin staining detected liver tissue damage in broilers. Predicted and verified the targeting relationship between miR-129-3p and SLC7A11 through miRDB and dual luciferase report experiments. The genes related to ferroptosis were detected by qRT-PCR and Western Blot. The results showed that the expression level of miR-129-3p mRNA in Se-deficient liver was significantly increased. To understand whether the miR-129-3p/SLC7A11 axis could involve in the process of ferroptosis, our further research showed that overexpression of miR-129-3p could reduce the expression of SLC7A11 and its downstream GCL, GSS, and GPX4, thereby inducing ferroptosis. These data indicates that miR-129-3p affected ferroptosis under Se deficiency conditions through the SLC7A11 pathway. Our research provides a new perspective for the mechanism of Se deficiency on the liver damage.

Hyperparathyroidism in a Large Cohort of Chinese Patients With Tumor-induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Hyperparathyroidism (HPT) including secondary HPT (SHPT) and tertiary HPT (THPT) in TIO patients, which is believed to be associated with phosphate supplementation, has not been well documented. OBJECTIVES: To clarify the prevalence, clinical characteristics, and risk factors for HPT in a large cohort of Chinese patients with TIO in our hospital. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study enrolled 202 patients with TIO. MAIN OUTCOME MEASUREMENTS: Occurrence of HPT in patients with TIO. RESULTS: HPT was observed in 91 patients (91/202, 45.1%): 84 patients (41.6%) with SHPT and 7 patients (3.5%) with THPT. All patients with THPT underwent parathyroidectomy and only 1 patient experienced recurrence. Compared with patients without HPT, patients with SHPT had longer disease duration, higher rate of phosphate and calcitriol supplementation, lower serum calcium, lower urine calcium excretion, and higher urine phosphate excretion. Compared with patients with SHPT, patients with THPT had even longer disease duration and a higher rate of phosphate and calcitriol supplementation. PTH levels showed positive correlation with intact FGF23 and 1,25-dihydroxyvitamin D levels, but not 25-hydroxy vitamin D level in patients with TIO. Multivariate logistic regression analysis showed that long disease duration and phosphate supplementation were independently associated with occurrence of HPT in patients with TIO. Further logistic regression analysis and restricted cubic spline model revealed dose-response relationship between cumulative dose of phosphate supplementation and PTH levels. CONCLUSIONS: HPT is common in patients with TIO. To avoid the occurrence of HPT in patients with TIO, timely diagnosis and tumor resection is necessary and an excessive dose of phosphate supplementation is not suggested before surgery.

Effects of multifaceted optimization management for chronic heart failure: a multicentre, randomized controlled study.

AIMS: In recent years, we have developed the concept of 'clinical pathway based on integrated traditional Chinese and western medicine for the management of Chronic heart failure (CHF)'. The purpose of this study was to assess the implementation effects of multifaceted optimization management of chronic heart failure. METHODS: A total of nine physicians in optimization group from nine research sites received multifaceted intervention (a 1-day training session on how to implement the optimization programme, a written optimization programme for CHF management, supervision from daily quality coordinator, and 1-monthly monitoring and feedback of performance measure) with respect to the management of CHF, comparing to nine physicians in control group who did not receive the aforementioned multifaceted intervention and diagnosed and treated CHF patients with conventional programme (usual care). After that, a total of 256 patients with CHF were enrolled and randomly assigned to receive optimization programme [integration of usual care and traditional Chinese medicine (TCM) treatment] or conventional programme (usual care) for the treatment of CHF. The primary outcome was the change in New York Heart Association (NYHA) functional classification during 24 weeks of treatment. RESULTS: When compared with usual care, multifaceted optimization management resulted in superior improvements in NYHA functional classification at the 12-week visit (P = 0.023), the 16-week, 20-week, and 24-week visits (P < 0.001). It also demonstrated superior performance in comparison with the conventional programme with respect to readmission rate for major adverse cardiovascular events (MACEs), readmission rate for worsening heart failure, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, left ventricular ejection fraction (LVEF), patient TCM syndrome scores, quality of life, and patients with heart failure with reduced ejection fraction (HFrEF) in optimization group more likely received beta-blockers and ACE inhibitors or ARBs than those in control group (P = 0.038 and P = 0.013, respectively). CONCLUSIONS: It is likely that the multifaceted optimization programme used in this study is feasible would benefit patients with CHF in NYHA functional classification, readmission for worsening heart failure, plasma NT-proBNP level, LVEF, patient TCM syndrome scores, and quality of life. Additionally, it would improve hospital personnel adherence to evidence-based performance measures for HFrEF.

Network Meta-analysis of oral Chinese patent medicines in treatment of acute exacerbation of chronic obstructive pulmonary disease / 中国中药杂志

This study aimed to evaluate the effectiveness and safety of eight oral Chinese patent medicines in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) by network Meta-analysis. Randomized controlled trial(RCT) on the treatment of AECOPD with eight oral Chinese patent medicines was retrieved from databases including CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library from database inception to August 6, 2022. The information was extracted from the included literature and the quality of the included studies was evaluated using the Cochrane risk of bias assessment tool. The data were analyzed using Stata SE 15.1 and ADDIS 1.16.8 software. Finally, 53 RCTs were included, with 5 289 patients involved, including 2 652 patients in the experimental group and 2 637 patients in the control group. Network Meta-analysis showed that Lianhua Qingwen Capsules+conventional western medicine were optimal in improving clinical effective rate, Shufeng Jiedu Capsules+conventional western medicine in improving FEV1/FVC, Qingqi Huatan Pills+conventional western medicine in improving FEV1%pred, Feilike Mixture(Capsules)+conventional western medicine in improving PaO_2, Lianhua Qingwen Capsules+conventional western medicine in reducing PaCO_2, and Qingqi Huatan Pills+conventional western medicine in reducing C-reactive protein(CRP). In terms of safety, most of them were gastrointestinal symptoms, and no serious adverse reactions were reported. When the clinical effective rate was taken as the comprehensive index of efficacy evaluation, Lianhua Qingwen Capsules+conventional western medicine were the most likely to be the best treatment for AECOPD. There are some limitations in the conclusion of this study. It only provides references for clinical medication.

Role of podocyte injury signaling pathway in steroid-resistant nephrotic syndrome and research progress in traditional Chinese medicine intervention / 中国中药杂志

As one of the main diseases leading to end-stage renal disease, steroid-resistant nephrotic syndrome(SRNS) can cause serious complications such as infection. Without effective control, this disease can further lead to the malignant development of the renal function, bringing serious social and economic burdens. As previously reported, the formation of SRNS is mostly related to the podocyte injury in the body, i.e., the injury of glomerular visceral epithelial cells. Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, nuclear transcription factor-κB(NF-κB) signaling pathway, mammalian target of rapamycin(mTOR)/adenosine monophosphate(AMP)-activated protein kinase(AMPK), transforming growth factor(TGF)-β1/Smads, and other signaling pathways are classical signaling pathways related to podocyte injury. By regulating the expression of signaling pathways, podocyte injury can be intervened to improve the adhesion between podocyte foot processes and glomerular basement membrane and promote the function of podocytes, thereby alleviating the clinical symptoms of SRNS. Through the literature review, traditional Chinese medicine(TCM) has unique advantages and an important role in intervening in podocyte injury. In the intervention in podocyte injury, TCM, by virtue of multi-target and multi-pathway role, can regulate and intervene in podocyte injury in many ways, alleviate the clinical symptoms of SRNS, and interfere with the progress of SRNS, reflecting the unique advantages of TCM. On the other hand, TCM can directly or indirectly inhibit podocyte injury by regulating the above signaling pathways, which can not only promote the effect of hormones and immunosuppressants and shorten the course of treatment, but also reduce the toxic and side effects caused by various hormones and immunosuppressants to exert the advantages of small side effects and low price of TCM. This article reviewed TCM in the treatment of SRNS by interfering with podocyte injury-related signaling pathways and is expected to provide a reference for the in-depth study of TCM in the treatment of SRNS, as well as a theoretical basis and a new direction for the clinical application of TCM to shorten the course of treatment of SRNS and delay the progression to end-stage renal disease.

Network-based pharmacology and molecular docking exploring the "Bupleuri Radix-Scutellariae Radix" mechanism of action in the viral hepatitis B treatment.

Viral hepatitis B is caused by the hepatitis B virus, which is characterized by liver lesions. Bupleuri Radix and Scutellariae Radix are the main traditional medicine pairs with remarkable efficacy in hepatitis B. However, their molecular mechanisms are incompletely understood. The main active components of Bupleuri Radix and Scutellariae Radix, as well as therapeutic targets for the treatment of hepatitis B, were identified through network pharmacology techniques. We identified viral hepatitis B targets using the GeneCards, online mendelian inheritance in man, and therapeutic target databases. We discovered the active components of Bupleuri Radix and Scutellariae Radix as well as therapeutic targets using the encyclopedia of traditional Chinese medicine, HERB, traditional Chinese medicine systems pharmacology database, and a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine databases. VENNY obtained the intersections. Cytoscape and STRING were used to create the "active ingredient-potential target" network and protein interaction network. The DAVID database was used to enrich GO and KEGG pathways. The results were confirmed using the molecular docking method. There were 1827 viral hepatitis B targets, and 37 active ingredients for Bupleuri and Scutellariae Radix, with the main components being quercetin, wogonin, baicalein, and kaempferol. Tumor necrosis factor (TNF), mitogen-activated protein kinase 3 (MAPK3), interleukin-6 (IL-6), vascular endothelial growth factor A, cysteinyl aspartate specific proteinase 3, transcription factor AP-1 (JUN), RAC-alpha serine/threonine-protein kinase, and cellular tumor antigen p53 are among the 78 common targets of Bupleuri Radix and Scutellariae Radix intervention in viral hepatitis B. KEGG enrichment resulted in 107 pathways, including cancer, hepatitis B, and TNF signaling pathways. According to the molecular docking technique, quercetin, wogonin, baicalein, and kaempferol had strong binding activities with TNF, MAPK3, and IL-6. In this study, we initially identified various molecular targets and multiple pathways involved in hepatitis B treatment with Bupleuri Radix and Scutellariae Radix.

[Current situation and outlook of acupuncture-moxibustion translational medicine under the background of multi-disciplinary intersection innovation].

The common development of multi-disciplinary intersection is a hot spot in the research of acupuncture- moxibustion translational medicine. This article analyzes the current situation and reasons for slow development of acupuncture-moxibustion translational medicine, takes acupuncture-moxibustion for depressive disorder as an example, takes acupuncture and moxibustion literature, clinical evidence-based, biological mechanism and medical equipment research and development as the main line, expounds potential strategies to promote the development of acupuncture-moxibustion translational medicine under the background of multi-disciplinary intersection innovation, and discusses the future research direction of acupuncture-moxibustion translational medicine.

Catalpol relieved angiotensin II-induced blood-brain barrier destruction via inhibiting the TLR4 pathway in brain endothelial cells.

CONTEXT: Catalpol is a major bioactive constituent of Rehmannia glutinosa Libosch (Scrophulariaceae), a traditional Chinese medicine, which is widely used in multiple diseases, including hypertension. OBJECTIVES: To explore whether catalpol protects against angiotensin II (Ang II)-triggered blood-brain barrier (BBB) leakage. MATERIALS AND METHODS: The bEnd.3 cells and BBB models were pre-treated with or without catalpol (50, 200 and 500 µM) or TAK-242 (1 µM) for 2 h and then with Ang II (0.1 µM) or LPS (1 µg/mL) for 24 h. Cell viability was determined by the MTT assay. The levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), caveolin-1 (Cav-1) and p-eNOS/eNOS were tested by western blot. The BBB permeability was evaluated by the flux of bovine serum albumin-fluorescein isothiocyanate (BSA-FITC) across monolayers. nuclear factor kappa-B (NF-κB) p65 nuclear translocation was explored by immunofluorescence staining. RESULTS: Ang II (0.1 µM) decreased the cell viability to 86.52 ± 1.79%, elevated the levels of TLR4, MyD88, iNOS, TNF-α and Cav-1 respectively to 3.7-, 1.5-, 2.3-, 2.2- and 2.7-fold, reduced the level of p-eNOS/eNOS to 1.6-fold in bEnd.3 cells, and eventually increased BBB permeability. Catalpol dose-dependently reversed these changes at 50-500 µM. Meanwhile, catalpol (500 µM) inhibited the upregulated levels of TLR4 pathway-related proteins and NF-κB p65 nuclear translocation, decreased the enhanced transcytosis, and relieved the BBB disruption caused by both LPS (the TLR4 activator) and Ang II. The effects are same as TAK-242 (the TLR4 inhibitor). CONCLUSIONS: Catalpol relieved the Ang II-induced BBB damage, which indicated catalpol has high potential for the treatment of hypertension-induced cerebral small vessel disease (cSVD).

TRIM67 Deficiency Exacerbates Hypothalamic Inflammation and Fat Accumulation in Obese Mice.

Obesity has achieved the appearance of a global epidemic and is a serious cause for concern. The hypothalamus, as the central regulator of energy homeostasis, plays a critical role in regulating food intake and energy expenditure. In this study, we show that TRIM67 in the hypothalamus was responsive to body-energy homeostasis whilst a deficiency of TRIM67 exacerbated metabolic disorders in high-fat-diet-induced obese mice. We found exacerbated neuroinflammation and apoptosis in the hypothalamus of obese TRIM67 KO mice. We also found reduced BDNF in the hypothalamus, which affected the fat sympathetic nervous system innervation and contributed to lipid accumulation in adipose tissue under high-fat-diet exposure. In this study, we reveal potential implications between TRIM67 and the hypothalamic function responding to energy overuptake as well as a consideration for the therapeutic diagnosis of obesity.

Network Pharmacology and Molecular Docking to Elucidate the Potential Mechanism of Ligusticum Chuanxiong Against Osteoarthritis.

Background: Osteoarthritis (OA) is a degenerative disease which serious affects patients. Ligusticum chuanxiong (CX) has been shown to have a certain curative effect on osteoarthritis in traditional Chinese medicine therapy. This study is based on network pharmacology and molecular docking technology to explore the potential mechanism of CX. Methods: Components of CX to treat osteoarthritis were screened in the TCMSP database and targets were predicted by the PharmMapper database, the osteoarthritis targets were collected from the GeneCards database, and intersection genes were found to be the possible targets of CX anti-OA. The STRING database and Cytoscape software were utilized for protein-protein interaction analysis and further screening of core targets. The Metascape database was used for KEGG and GO enrichment analyses. Then, the top 10 pathways were selected to construct "drug-compound-target-pathway-disease" network analysis. Finally, molecular docking was used to analyze the binding affinity of seven compounds with core targets and TNF-α. Results: Seven compounds with 253 non-repetitive targets of CX were screened from the TCMSP database and 60 potential intersection targets of CX anti-OA were found. PPI network analysis showed that the core targets were ALB, AKT1, IGF1, CASP3, MAPK1, ANXA5, and MAPK14, while GO and KEGG pathway enrichment analyses showed that the relevant biological processes involved in the treatment of osteoarthritis by CX might include the MAPK cascade and reactive oxygen species metabolic process. The KEGG pathway analysis result was mainly associated with the MAPK signaling pathway and PI3K-AKT signaling pathway. We further docked seven ingredients with MAPK1 and MAPK14 enriched in the MAPK pathway, and TNF-α as the typical inflammatory cytokine. The results also showed good binding affinity, especially FA, which may be the most important component of CX anti-OA. Conclusion: Our research revealed the potential mechanism of CX in the treatment of OA, and our findings can also pave the way for subsequent basic experimental verification and a new research direction.