Vitamin D supplementation could enhance the effectiveness of glibenclamide in treating type 2 diabetes by improving the function of pancreatic ß-cells through the NF-κB pathway.

PURPOSE: The high morbidity and mortality associated with type 2 diabetes mellitus (T2DM) pose a significant global health challenge, necessitating the development of more efficient anti-diabetic drugs with fewer side effects. This study investigated the intervention of vitamin D3 combined with glibenclamide in rats with T2DM to elucidate its effects on pancreatic ß-cells through the NF-κB pathway. METHODS: Twenty-four healthy male Sprague-Dawley (SD) rats were randomly assigned to four groups: the control group (CG), the model group (MG), the glibenclamide group (GG), and the glibenclamide + vitamin D3 group (GDG). After inducing the T2DM model using high-fat and high-sugar diet and intraperitoneal injection of streptozotocin, the rats in the GG group were administered glibenclamide orally (0.6 mg/kg/day), while those in the GDG group received both glibenclamide (0.6 mg/kg/day) and vitamin D3 (500 IU/kg/day) in corn oil for a duration of 8 weeks. Biochemical indices were measured, and histopathological changes in pancreatic tissue and islet ß cells were observed using hematoxylin and eosin staining. The expression of pancreatic nuclear factor κB (NF-κB), islet ß-cells, and inflammatory cytokines were assessed using the TUNEL method and PCR. RESULTS: According to the data from this current study, the GDG group showed significant positive differences in plasma biochemical indices, as well as in the expression of ß cells, NF-κB p65, TNF-α, IL-1ß, INF-γ, and Fas, compared to the GG and CG groups (P < 0.05). CONCLUSION: The results suggest that vitamin D has beneficial effects on T2DM by improving the functions of islet ß cells through inhibition of the NF-κB signaling pathway. Therefore, it is suggested that vitamin D supplementation, when used alongside antidiabetic drugs, may more effectively prevent and treat T2DM.

Effect of governor vessel moxibustion (GVM) therapy with mild to moderate psoriasis: A randomized clinical trial.

BACKGROUND: It was hypothesized that governor vessel moxibustion (GVM) therapy may improve the course of mild to moderate psoriasis (PS) in patients. METHODS: A randomized, controlled clinical trial lasting 40 days was conducted at the Shaanxi Provincial Hospital of Chinese Medicine. Investigators were blinded to patient groupings. Individuals with mild to moderate PS ranging in age from 18 to 70 years were enrolled. GVM therapy was administered one every 10 days for 40 days with 1.5 hours on the governor meridian in the GVM therapy group. The PS area and severity index (PASI) and dermatological life quality index (DLQI) scores were monitored before and after treatment. RESULTS: There was a significant reduction in the mean PASI score in the GVM therapy group of 0.76 points (2.37 [2.61]; SE, 0.39) after 40 days of treatment compared with the control group (3.12 [2.12], SE, 0.32) (P < .01). There were also significantly greater changes in the DLQI scores of the GVM therapy group (4.23 [2.25]; SE, 0.34) compared with those in the control group (8.91 [3.85]; SE, 0.59) (P < .001). CONCLUSION: GVM therapy effectively reduced both PASI and DLQI scores in patients with mild to moderate PS.

The effect of enteral nutrition nursing intervention on postoperative treatment of chronic critically ill patients: Health prevention data analysis.

The field of genomics has witnessed remarkable advancements, leading to the gradual clarification of the genetic mechanism underlying various cancers. As a result, there has been an increased emphasis on gene prevention and treatment. Against this backdrop, this paper aims to examine the impact of enteral nutrition nursing intervention on the postoperative treatment of patients with chronic critical illness, with a focus on health prevention. Based on an analysis of the clinical data of patients with chronic critical illness, the study found that enteral nutrition nursing intervention plays a crucial role in enhancing the nutritional status of patients, reducing the incidence of complications, shortening the length of hospital stay, and improving the effect of postoperative rehabilitation. The study's results provide valuable insights into the efficacy of enteral nutrition nursing intervention in the postoperative treatment of patients with chronic critical illness. By improving the nutritional status of patients, enteral nutrition nursing intervention can help reduce the risk of complications, shorten the length of hospital stay, and enhance the effectiveness of postoperative rehabilitation. These findings underscore the importance of adopting effective interventions such as enteral nutrition nursing to improve the therapeutic outcomes of chronic critical illness patients and achieve the goal of health prevention.

Banzhilian formula alleviates psoriasis-like lesions via the LCN2/MMP-9 axis based on transcriptome analysis.

Introduction: Oral Banzhilian formula (BZLF) is effective in the clinical treatment of psoriasis. However, the effectiveness and mechanism of different drug delivery routes deserve further study. Methods: First, we established the mouse model of psoriasis using imiquimod (IMQ), and high-performance liquid chromatography (HPLC) was used for the quality control of BZLF. Secondly, Total RNA Sequencing and bioinformatics analysis were used to explore the regulatory mechanism of BZLF in improving psoriatic lesions. Finally, further verification was based on animal experiments. Results: we externally applied BZLF for skin lesions in an imiquimod-induced psoriasis mouse model and found that BZLF alleviated psoriasis-like skin lesions while inhibiting the expression of Ki67 and inflammatory factors (Il17a, Tnf-α, S100a7 and Cxcl1) in skin lesions. Transcriptome sequencing results suggested that BZLF inhibited signalling pathways closely related to psoriatic inflammation, such as the IL-17 signalling pathway, chemokine signalling pathway, TNF signalling pathway, and NF-kappa B signalling pathway, and the protein-protein interaction (PPI) network identified LCN2 as one of the core target genes and screened out its regulated downstream gene MMP9. Discussion: Our findings suggest that the anti-psoriatic mechanism of BZLF involved in downregulating the LCN2/MMP-9 axis.

Polygoni Multiflori Radix interferes with bile acid metabolism homeostasis by inhibiting Fxr transcription, leading to cholestasis.

Objective: To explore the possible mechanisms of cholestasis induced by Polygoni Multiflori Radix (PM). Methods: Low and high doses of water extract of PM were given to mice by gavage for 8 weeks. The serum biochemical indexes of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyltransferase (GGT) alkaline phosphatase (ALP) and so on were detected in the second, fourth, sixth, and eighth weeks after administration. At the end of the eighth week of administration, the bile acid metabolic profiles of liver and bile were screened by high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS). Liver pathological changes were observed by hematoxylin and eosin staining. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA transcription of the target genes and Western blotting (WB) was used to the detect target protein expression. Results: Biochemical tests results showed the values of ALP and GGT were two and three times greater than the normal values respectively, and the value of R was less than 2. Histopathology also showed that PM caused lymphocyte infiltration, a small amount of hepatocyte necrosis and nuclear fragmentation in mouse liver. The proliferation of bile duct epithelial cells was observed in the high group. These results indicated that PM may lead to cholestatic liver injury. HPLC-QQQ-MS/MS analysis with the multivariate statistical analysis revealed significant alterations of individual bile acids in liver and gallbladder as compared to those of the control group. RT-qPCR showed that the transcription of Fxr, Shp, Bsep, Bacs, Mdr2, and Ugt1a1 were downregulated and that of Cyp7a1, Mrp3, and Cyp3a11 was significantly upregulated in the treatment group. WB demonstrated that PM also markedly downregulated the protein expression of FXR, BSEP, and MDR2, and upregulated CYP7A1. Conclusion: PM inhibited the expression of FXR, which reduced the expression of MDR2 and BSEP, leading to the obstruction of bile acids outflow, and increased the expression of CYP7A1, resulting in an increase of intrahepatic bile acid synthesis, which can lead to cholestasis.

Association between environmental chemicals co-exposure and peripheral blood immune-inflammatory indicators.

Chronic inflammation is closely related to chronic inflammatory diseases, autoimmune diseases and cancer. Few studies have evaluated the effects of exposure to multiple chemical combinations on immunoinflammatory related indicators and their possible molecular mechanisms. This study explored the effect of exposure to various chemicals on immune-inflammatory biomarkers and its molecular mechanism. Using data from 1,723 participants in the National Health and Nutrition Examination Survey (NHANES, 2011-2012), the aim was to determine the association between chemical mixtures and immunoinflammatory biomarkers [including White blood cell (Wbc), neutrophil (Neu), lymphocytes (Lym), and Neutrophil-to-lymphocyte ratio (NLR)] using linear regression model, weighted quantile sum regression (WQSR) model, and bayesian nuclear machine regression (BKMR) model. Meanwhile, functional enrichment analysis and protein-protein interaction network establishment were performed to explore the molecular mechanism of inflammation induced by high-weight chemicals. In the linear regression model established for each single chemical, the four immunoinflammatory biomarkers were positively correlated with polycyclic aromatic hydrocarbons (PAHs), negatively correlated with perfluoroalkyl substances (PFASs), and positively or negatively correlated with metallic and non-metallic elements. WQSR model showed that cadmium (Cd), perfluorooctane sulfonic acid (PFOS) and perfluorodecanoic acid (PFDE) had the highest weights. In BKMR analysis, the overall effect of chemical mixtures was significantly associated with Lym and showed an increasing trend. The hub genes in high-weight chemicals inflammation-related genes were interleukin-6 (IL6), tumor necrosis factor (TNF), and interleukin-1B (IL1B), etc. They were mainly enriched in inflammatory response, Cytokine-cytokine receptor interaction, Th17 cell differentiation and IL-17 signaling pathway. The above results show that exposure to environmental chemical cocktails primarily promotes an increase in Lym across the immune-inflammatory spectrum. The mechanism leading to the inflammatory response may be related to the activation of IL-6 amplifier by the co-exposure of environmental chemicals.

Danhe granule ameliorates nonalcoholic steatohepatitis and fibrosis in rats by inhibiting ceramide de novo synthesis related to CerS6 and CerK.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhe granule (DHG) is used by Chinese doctors to treat blood stasis, phlegm and dampness. Its lipid-lowering ability has been investigated in our previous research. However, the anti-liver inflammatory and fibrotic effects and mechanism of action of DHG in non-alcoholic steatohepatitis (NASH) have not been explored. AIM OF THE STUDY: To evaluate the ameliorative effects of DHG on liver inflammation and fibrosis in a methionine/choline-deficient (MCD) diet-induced NASH rat model, and its underlying mechanism. MATERIALS AND METHODS: Sprague-Dawley rats were fed an MCD diet for two weeks and then treated with or without DHG by oral gavage for eight weeks. Their body weight and liver index were measured. The serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activities as well as the liver triglyceride (TG) and free fatty acid (FFA) levels were tested using reagent kits. Inflammatory cytokines, including Tnf-α, Il-ß and Il-6, and fibrosis genes, including Acta2, Col1a1, Col1a2 and Tgf-ß were examined by real-time quantitative PCR (RT-qPCR). Hematoxylin-eosin (H&E), Oil Red O, Masson's and Sirius Red staining were used to observe liver changes. The plasma and liver ceramide levels were analyzed using HPLC-QQQ-MS/MS. The expression of serine palmitoyl-CoA transferase (Spt), ceramide synthase 6 (Cers6), dihydroceramide desaturase 1 (Des1), glucosylceramide synthase (Gcs), and ceramide kinase (Cerk) mRNA was assayed by RT-qPCR, while the protein expression of CerS6, DES1, GCS, CerK, and casein kinase 2α (CK2α) was tested by western blotting (WB). CerS6 degradation was evaluated using a cycloheximide (CHX) assay in vitro. RESULTS: The liver index decreased by 20% in DHG groups and the serum ALT and AST decreased by approximately 50% and 30%, respectively in the DHG-H group. The liver Oil Red O staining, TG, and FFA changes showed that DHG reduced hepatic lipid accumulation by approximately 30% in NASH rats. H&E, Masson's and Sirius Red staining and the mRNA levels of Tnf-α, Il-ß, Il-6, Acta2, Col1a1, Col1a2 and Tgf-ß revealed that DHG alleviated liver inflammation and fibrosis in NASH rats. The ceramide (Cer 16:0), and hexosylceramide (HexCer 16:0, HexCer 18:0, HexCer 22:0, HexCer 24:0 and HexCer 24:1) levels decreased by approximately 17-56% in the plasma of the DHG-M and H rats. The Cer 16:0 content in the liver decreased by 20%, 50%, and 70% with the DHG-L, M, and H treatments; additionally, the dhCer 16:0, Cer 18:0, HexCer 18:0, HexCer 20:0 Cer 22:0-1P, Cer 24:0-1p, Cer 24:1-1p, and Cer 26:1-1p levels decreased in the DHG groups. The mRNA and protein expression levels of DES1, GCS, Cerk, CerS6, and CHX assay indicated that DHG decreased the mRNA and protein expression levels of CerK and reduced CerS6 protein expression by promoting its degradation. Additionally, DHG attenuated the protein expression of CK2α which could increase CerS6 enzymatic activity by phosphorylating its C-terminal region. CONCLUSION: DHG ameliorated the levels of liver FFA and TG and inflammation and fibrosis in MCD-induced rats, which were associated with decreasing ceramide species in the plasma and liver by reducing the expression levels of CerS6 and CerK.

Identification of Potential Biomarkers and Small Molecule Drugs for Cutaneous Melanoma Using Integrated Bioinformatic Analysis.

Background: Cutaneous melanoma (CM) is a type of skin cancer with a high fatality rate, and its pathogenesis has not yet been fully elucidated. Methods: We obtained the gene expression datasets of CM through the Gene Expression Omnibus (GEO) database. Subsequently, robust rank aggregation (RRA) method was used to identify differentially expressed genes (DEGs) between CM cases and normal skin controls. Gene functional annotation was performed to explore the potential function of the DEGs. We built the protein-protein interaction (PPI) network by the Interactive Gene database retrieval tool (STRING) and selected hub modules by Molecular Complexity Detection (MCODE). We furthered and validated our results using the TCGA-GTEX dataset. Finally, potential small molecule drugs were predicted by CMap database and verified by molecular docking method. Results: A total of 135 DEGs were obtained by RRA synthesis analysis. GMPR, EMP3, SLC45A2, PDZD2, NPY1R, DLG5 and ADH1B were screened as potential targets for CM. Furazolidone was screened as a potential small molecule drug for the treatment of CM, and its mechanism may be related to the inhibition of CM cell proliferation by acting on GMPR. Conclusion: We identified seven prognostic therapeutic targets associated with CM and furazolidone could be used as a potential drug for CM treatment, providing new prognostic markers, potential therapeutic targets and small molecule drugs for the treatment and prevention of CM.

Biogenesis, Trafficking, and Function of Small RNAs in Plants.

Small RNAs (sRNAs) encoded by plant genomes have received widespread attention because they can affect multiple biological processes. Different sRNAs that are synthesized in plant cells can move throughout the plants, transport to plant pathogens via extracellular vesicles (EVs), and transfer to mammals via food. Small RNAs function at the target sites through DNA methylation, RNA interference, and translational repression. In this article, we reviewed the systematic processes of sRNA biogenesis, trafficking, and the underlying mechanisms of its functions.

Discovery of Hepatotoxic Equivalent Markers and Mechanism of Polygonum multiflorum Thunb. by Metabolomics Coupled with Molecular Docking.

Polygonum multiflorum Thunb. (PMT), a commonly used Chinese herbal medicine for treating diseases such as poisoning and white hair, has attracted constant attention due to the frequent occurrence of liver injury incidents. To date, its hepatotoxic equivalent markers (HEMs) and potential hepatotoxic mechanisms are still unclear. In order to clarify the HEMs of PMT and further explore the potential mechanisms of hepatotoxicity, firstly, the chemical constituents in PMT extract were globally characterized, and the fingerprints of PMT extracts were established along with the detection of their hepatotoxicity in vivo. Then, the correlations between hepatotoxic features and component contents were modeled by chemometrics to screen HEMs of PMT, which were then further evaluated. Finally, the hepatotoxic mechanisms of PMT were investigated using liver metabolomics and molecular docking. The results show that the chemical combination of 2,3,5,4-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) and emodin-8-O-glucoside (EG) was discovered as the HEMs of PMT through pre-screening and verifying process. Liver metabolomics revealed that PMT caused liver injury by interfering with purine metabolism, which might be related to mitochondrial function disorder and oxidative injury via the up-regulations of xanthosine and xanthine, and the down-regulation of 5' nucleotidase (NT5E) and adenylate kinase 2 (AK2). This study not only found that the HEMs of PMT were TSG and EG, but also clarified that PMT might affect purine metabolism to induce liver injury, which contributed to our understanding of the underlying mechanisms of PMT hepatotoxicity.

Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness.

CONTEXT: Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba (Crassulaceae) is used to prevent and treat acute mountain sickness. However, the mechanisms underlying its effects on the central nervous system remain unclear. OBJECTIVE: To investigate the effect of Rhodiola crenulata on cellular metabolism in the central nervous system. MATERIALS AND METHODS: The viability and Hif-1α levels of microglia and neurons at 5% O2 for 1, 3, 5 and 24 h were examined. We performed the binding of salidroside (Sal), rhodiosin, tyrosol and p-hydroxybenzyl alcohol to Hif-1α, Hif-1α, lactate, oxidative phosphorylation and glycolysis assays. Forty male C57BL/6J mice were divided into control and Sal (25, 50 and 100 mg/kg) groups to measure the levels of Hif-1α and lactate. RESULTS: Microglia sensed low oxygen levels earlier than neurons, accompanied by elevated expression of Hif-1α protein. Salidroside, rhodiosin, tyrosol, and p-hydroxybenzyl alcohol decreased BV-2 (IC50=1.93 ± 0.34 mM, 959.74 ± 10.24 µM, 7.47 ± 1.03 and 8.42 ± 1.63 mM) and PC-12 (IC50=6.89 ± 0.57 mM, 159.28 ± 8.89 µM, 8.65 ± 1.20 and 8.64 ± 1.42 mM) viability. They (10 µM) reduced Hif-1α degradation in BV-2 (3.7-, 2.5-, 2.9- and 2.5-fold) and PC-12 cells (2.8-, 2.8-, 2.3- and 2.0-fold) under normoxia. Salidroside increased glycolytic capacity but attenuated oxidative phosphorylation. Salidroside (50 and 100 mg/kg) treatment increased the protein expression of Hif-1α and the release of lactate in the brain tissue of mice. CONCLUSIONS: These results suggest that Sal induces metabolic reprogramming by regulating the Hif-1α signalling pathway to activate compensatory responses, which may be the core mechanism underlying the effect of Rhodiola crenulata on the central nervous system.

Adipocyte factor CTRP6 inhibits homocysteine-induced proliferation, migration, and dedifferentiation of vascular smooth muscle cells through PPARγ/NLRP3.

NLRP3 and PPARγ play important roles in the development of atherosclerosis (AS). Studies have shown that PPARγ regulates the expression of NLRP3 in vascular diseases. In addition, the adipocyte factor CTRP6 can improve the activation of PPARγ in vascular diseases. However, the regulatory relationship between CTRP6, PPARγ, and NLRP3 in AS and its underlying mechanism have not been reported. Since proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) are key events in AS, in this study, we induced proliferation, migration, and dedifferentiation of VSCMs through homocysteine (HCY) to detect the specific effects of CTRP6, PPARγ, and NLRP3. Subsequently, CTRP6 was overexpressed and the PPARγ inhibitor GW9662 and agonist rosiglitazone were administered to HCY-induced VSCMs to investigate the mechanisms. The results show that the expression of CTRP6 decreased in HCY-induced VSMCs. In addition, CTRP6 overexpression inhibited the proliferation and migration of HCY-induced VSMCs, as well as cell cycle acceleration and dedifferentiation. Overexpression of CTRP6 increased HCY-induced PPARγ expression and inhibited NLRP3 expression. The addition of GW9662 and rosiglitazone further demonstrated that overexpression of CTRP6 inhibited HCY-induced VSMC proliferation, migration, and dedifferentiation through PPARγ/NLRP3 signaling. In conclusion, CTRP6 inhibited HCY-induced proliferation, migration, and dedifferentiation of VSMCs through PPARγ/NLRP3.

Identification of Potential Biomarkers for Psoriasis by DNA Methylation and Gene Expression Datasets.

DNA methylation (DNAm) plays an important role in the pathogenesis of psoriasis through regulating mRNA expressions. This study aimed to identify hub genes regulated by DNAm as biomarkers of psoriasis. Psoriatic skin tissues gene expression and methylation datasets were downloaded from Gene Expression Omnibus (GEO) database. Subsequently, multiple computational approaches, including immune infiltration analysis, enrichment analysis, protein-protein interaction (PPI) network establishment, and machine learning algorithm analysis (lasso, random forest, and SVM-RFE), were performed to analyze the regulatory networks, to recognize hub genes, and to clarify the pathogenesis of psoriasis. Finally, the hypermethylated genes were used to immune cell infiltration analysis, which revealed that psoriasis skin tissues were mainly composed of activated dendritic cells, resting mast cells, T follicular helper cells (cTfh), etc. Differentially expressed-methylated genes (DEMGs) were identified and partitioned into four subgroups and the 97 significantly hypermethylated and downregulated (hyper-down) genes accounted for the highest proportion (47%). Hyper-down genes were mainly enriched in glucose homeostasis, AMP-activated protein kinase (AMPK) signaling pathway, lipid storage disease, partial lipodystrophy, and insulin resistance. Furthermore, insulin receptor substrate 1 (IRS1), Rho guanine nucleotide exchange factor 10 (ARHGEF10) and retinoic acid induced 14 (RAI14) were identified as potential targets. These findings provided new ideas for future studies of psoriasis on the occurrence and the molecular mechanisms.

Epigenetics in psoriasis: perspective of DNA methylation.

Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation of keratinocytes (KCs). Onset of psoriasis is related to genetic, immune and environmental factors. The environment can interact with the genome through epigenetic modifications, including DNA methylation, and this modification is involved in the pathogenesis of psoriasis. In addition to a skin disease, psoriasis is also considered a systemic disease. We reviewed the current literature of psoriatic DNA methylation for studies from several aspects on the DNA methylation distribution patterns in different tissues/cells, single-nucleotide polymorphisms, and candidate disease genes and identified target genes regulated by DNA methylation that have been directly/indirectly validated. This review contributes to a comprehensive understanding of the important a role that DNA methylation plays in psoriasis from a holistic perspective and will promote the implementation of DNA methylation in diagnostic and therapeutic strategies for psoriatic patients.

Qinzhuliangxue mixture alleviates psoriasis-like skin lesions via inhibiting the IL6/STAT3 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory skin disease mediated by immunity. Our pre-clinical studies have proved that QZLX mixture can improve patients' clinical symptoms with psoriasis without noticeable adverse reactions. In a psoriasis-like mouse model induced by imiquimod, QZLX mixture has been shown to alleviate epidermal inflammation and inhibit the hyperproliferation of keratinocytes. However, its related molecular mechanism remains to be elucidated. AIM OF THE STUDY: To assess the mechanism of QZLX mixture against psoriasis. MATERIALS AND METHODS: This study combines network pharmacology and experiments to study the mechanism of QZLX against psoriasis. First, construct the active compound-target network and PPI network. Secondly, determine possible drug targets through Molecular docking and KEGG. Thirdly, high-performance liquid chromatography (HPLC) was used for the quality control of QZLX. Finally, use a mouse model of psoriasis to further confirm the role of QZLX. RESULTS: (1) Network pharmacology analysis shows that QZLX alleviates psoriasis's epidermal inflammation, and neovascularization may be achieved by inhibiting the IL6/STAT3 signaling pathway. (2) QZLX improves the pathological characteristics of IMQ-induced skin damage in psoriasis-like mice. (3) QZLX inhibits the IL6/STAT3 signaling pathway and reduces the expression of IL-17, IL-23, and TNF-α related to inflammation in peripheral blood, as well as the expression of S100A7 in the lesion area. QZLX is better than MTX in inhibiting neovascularization by down-regulating the expression of HIF-1 and CD31 in the lesion area. Finally, inhibition of Ki67 alleviates the excessive proliferation of keratinocytes. CONCLUSION: In sum, this study clarifies the mechanism of QZLX against psoriasis and provides evidence to support its clinical use.

Fabrication of hollow flower-like magnetic Fe3O4/C/MnO2/C3N4 composite with enhanced photocatalytic activity.

The serious problems of environmental pollution and energy shortage have pushed the green economy photocatalysis technology to the forefront of research. Therefore, the development of an efficient and environmentally friendly photocatalyst has become a hotpot. In this work, magnetic Fe3O4/C/MnO2/C3N4 composite as photocatalyst was synthesized by combining in situ coating with low-temperature reassembling of CN precursors. Morphology and structure characterization showed that the composite photocatalyst has a hollow core-shell flower-like structure. In the composite, the magnetic Fe3O4 core was convenient for magnetic separation and recovery. The introduction of conductive C layer could avoid recombining photo-generated electrons and holes effectively. Ultra-thin g-C3N4 layer could fully contact with coupled semiconductor. A Z-type heterojunction between g-C3N4 and flower-like MnO2 was constructed to improve photocatalytic performance. Under the simulated visible light, 15 wt% photocatalyst exhibited 94.11% degradation efficiency in 140 min for degrading methyl orange and good recyclability in the cycle experiment.

Efficacy and safety of fire needle therapy for blood stasis syndrome of plaque psoriasis: protocol for a randomized, single-blind, multicenter clinical trial.

BACKGROUND: Fire needle therapy is a characteristic treatment in traditional Chinese medicine (TCM). An increasing number of studies have indicated that fire needle treatment for psoriasis provides satisfactory results with few side effects and a low recurrence rate. We herein describe the protocol for a multicenter, randomized, single-blind, placebo-controlled trial that will provide high-quality evidence on the efficacy and safety of fire needle therapy for plaque psoriasis. METHODS: Ninety-two patients with blood stasis syndrome (BSS) of plaque psoriasis will be enrolled and randomly assigned to receive fire needle therapy (intervention group) or fire needle control therapy (control group) once a week for 4 weeks. The Psoriasis Area and Severity Index (PASI) score will serve as the major efficacy index, while the body surface area (BSA), Physician Global Assessment (PGA) score, Dermatology Life Quality Index (DLQI) score, patient-reported quality of life (PRQoL), visual analog scale (VAS) score for itching, TCM symptom score, and relapse rate will be assessed as secondary outcomes. The PASI score, BSA, PGA score, and VAS score for itching will be evaluated at baseline and during the 4-week treatment and follow-up periods. DLQI score, PRQoL, and TCM symptom score will be assessed at baseline and during the treatment period. Recurrence will be evaluated during the follow-up period. Safety assessments include vital sign monitoring, routine blood tests, blood biochemistry, routine urine tests, pregnancy tests, physical examinations, and adverse-event recording. SAS software will be used for data analysis. The data network platform will be designed by the data management center of Nanjing Ningqi Medical Technology Co., Ltd. DISCUSSION: It is believed that fire needle therapy can activate the meridians, promote blood circulation, and regulate skin immunity. BSS of plaque psoriasis is related to not only immune dysfunction but also poor or stagnant blood flow. We anticipate that the results of the trial described in this protocol will provide strong evidence for the safety and efficacy of fire needle therapy for BSS of plaque psoriasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03953885 . Registered on May 15, 2019. Name: Fire Needle Therapy on Plaque Psoriasis with Blood Stasis Syndrome.

[Quantification of aristolochic acids and their DNA adducts in mice kidney and liver by HPLC-MS/MS].

This study aims to establish a quantitative method of 4 aristolochic acids-DNA adducts in mice kidney and liver based on high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) for monitoring the content changes of aristolochic acids-DNA adducts. A Shiseido Capcellpak AQ C_(18) column(3 mm×100 mm, 3 µm) was used, with a mixture of 0.2% acetic acid-5 mmol·L~(-1) ammonium acetate as the aqueous phase and methanol as the organic phase for gradient elution. The multiple reaction monitoring(MRM) scanning method under positive mode by electrospray ionization(ESI) was performed for the detection of the aristolochic acids-DNA adducts which formed by combining aristolochic acid Ⅰ/Ⅱ with deoxyadenosine, deoxyguanosine, and deoxycytidine, respectively. Balb/c mice were given Guanmutong extract by gavage, and the relative content of aristolochic acids-DNA adducts in liver and kidney samples were analyzed within 60 days. It was found that the concentration of 4 aristolochic acids-DNA adducts in the kidney was significantly higher than that in the liver, and there were about 15.87 adducts in per 1×10~6 normal deoxynucleosides, which was 4.5-7.5 times than that of the liver. What's more, some adducts can still be detected on the 30 th day after administration. The concentration of the adducts in the liver was highest on the first day after administration, and a second peak appeared during the 7 th to 14 th days. The results indicated that aristolochic acids-DNA adducts are difficult to eliminate in vivo, and it is of great significance to study the mechanism of liver and kidney injury of aristolochic acid.

Proteomics Unravels Emodin Causes Liver Oxidative Damage Elicited by Mitochondrial Dysfunction.

Emodin is one of the main active compounds in many Chinese traditional herbs. Due to its potential toxic effect on the liver, the possible injury mechanism needs to be explored. In the present study, we investigated liver injury mechanisms of emodin on rats by the technology of proteomics. Firstly, 4530 proteins were identified from the liver of rats treated with emodin by label free proteomics. Inside, 892 differential proteins were selected, presenting a downward trend. Bioinformatics analysis showed that proteins interfered with by emodin were mainly involved in oxidation-reduction biological processes and mitochondrial metabolic pathways, such as mitochondrial fatty acid ß-oxidation, citric acid cycle, and oxidative phosphorylation, which were further confirmed by western blot. The decrease in maximal respiration, ATP production, spare respiratory capacity, and coupling efficiency and increase in proton leakage were detected by seahorse XFe 24 analyzer, which confirmed the damage of mitochondrial function. The down-regulated expressions in antioxidant proteins were verified by western blot and a significant increase of ROS levels were detected in emodin group, which showed that emodin disrupted redox homeostasis in livers. Molecular docking revealed that the main targets of emodin might be acadvl and complex IV. Generally, emodin could induce oxidative stress in livers by directly targeting acadvl/complex IV and inhibiting fatty acid ß-oxidation, citric acid cycle, and oxidative phosphorylation taken place in mitochondria.

Investigation of the Lipid-Lowering Mechanisms and Active Ingredients of Danhe Granule on Hyperlipidemia Based on Systems Pharmacology.

OBJECTIVE: Investigate the active ingredients and underlying hypolipidemic mechanisms of Danhe granule (DHG). METHODS: The lipid-lowering effect of DHG was evaluated in hyperlipidemic hamsters induced by a high-fat diet. The ingredients absorbed into the blood after oral administration of DHG in hamsters were identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). A systems pharmacology approach incorporating target prediction and network construction, gene ontology (GO) enrichment and pathway analysis was performed to predict the active compounds and map the compounds-targets-disease network. Real-time polymerase chain reaction (RT-PCR) and Western blot were utilized to analyze the mRNA and protein expression levels of predicted targets. RESULTS: DHG remarkably lowered the levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and arteriosclerosis index (AI), at the same time, elevated the levels of serum high-density lipoprotein cholesterol (HDL-c) and HDL-c/TC ratio in hyperlipidemic hamsters. Sixteen ingredients absorbed into blood after oral administration of DHG were identified as the possible components interacted with targets. Moreover, 65 potential targets were predicted after targets intersection and compounds-targets-disease network mapping. Then, compounds-targets-pathways network mapping revealed that six active compounds (emodin, naringenin, etc.) compounds could interact with 10 targets such as sterol regulatory element binding protein (SREBP) 1c, SREBP-2 and peroxisome proliferation-activated receptor (PPAR) α, regulate three lipid metabolism-related pathways including SREBP control of lipid synthesis pathway, PPAR signaling pathway and nuclear receptors in lipid metabolism and toxicity pathway, and further affect lipid metabolic processes including fatty acid biosynthesis, low-density lipoprotein receptor (LDLR)-mediated cholesterol uptake, bile acid biosynthesis, and cholesterol efflux. Experimental results indicated that DHG significantly increased SREBP-2, LDLR, PPARα, liver X receptor alpha (LXRα), cholesterol 7α-hydroxylase (CYP7A1), and ATP binding cassette subfamily A member 1 (ABCA1) mRNA and protein expressions while decreased SREBP-1c and fatty acid synthase (FAS) mRNA, and protein expressions. CONCLUSION: DHG possessed a good hypolipidemic effect that may be through affecting the mRNA and protein expressions of SREBP-1c, FAS, SREBP-2, LDLR, PPARα, LXRα, CYP7A1, and ABCA1, involving in fatty acid synthesis, LDLR-mediated cholesterol uptake, bile acid biosynthesis, and cholesterol efflux. This study further provided experimental evidence about its practical application for treating hyperlipidemia and its complications.