This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL^-1) were used to induce fibrotic model, and high glucose (30 mmol·L^-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

AIM To investigate the ameliorative effects of Schisandrol A(Sol A)in Suhuang antitussive capsule on post-infectious cough(PIC).METHODS The in vivo mouse PIC model was established by intratracheal instillation of lipopolysaccharide(LPS)combined with cigarette smoke exposure.The mice were randomly divided into the control group,the model group,the Suhuang antitussive capsule group(14 g/kg),the montelukast sodium positive control group(3 mg/kg),and low and high dose Sol A groups(10,30 mg/kg).The in vitro PIC model was established by stimulating human bronchial epithelial cells(BEAS-2B)with LPS.The cells were divided into the control group,the model group,the Suhuang antitussive capsule group(10 μg/mL)and low and high dose Sol A groups(3,10 μmol/L).HE and Masson staining were used to detect the pathological changes of the lung and bronchial tissues.ELISA was used to detect the levels of IL-1β,IL-6,TNF-α,ROS,MDA,SOD and GSH in the lung tissues.RT-qPCR was used to detect the IL-1β,IL-6 and TNF-α mRNA expressions in BEAS-2B cells.And Western blot was applied to detect the protein expressions of p-PI3K,p-Akt,NOX4,SIRT1,p-ERK,Fibronectin,E-cadherin,Vimentin and α-SMA in mouse lung tissue and BEAS-2B cells.RESULTS Compared with the model group,the groups intervened with Sol A or Suhuang antitussive capsule displayed prolonged cough latency(P＜0.01);reduced cough frequency(P＜0.01);relieved pulmonary inflammatory cell infiltration and collagen deposition in PIC mice;decreased pulmonary levels of IL-1β,IL-6,TNF-α,ROS,MDA and protein expressions of Fibronectin,Vimentin,α-SMA,p-ERK,p-PI3K,p-Akt,and NOX4(P＜0.05,P＜0.01);increased pulmonary levels of SOD and GSH and protein expressions of E-cadherin and SIRT1(P＜0.05,P＜0.01);decreased ROS level,IL-1β,IL-6,TNF-α mRNA expressions and p-ERK,p-PI3K,p-Akt,NOX4 protein expressions in vitro(P＜0.05,P＜0.01);and increased SIRT1 protein expression in vitro as well(P＜0.01).CONCLUSION Being the main antitussive component of Suhuang antitussive capsule upon the PIC model,Sol A inhibits the inflammation via SIRT1/ERK signaling pathway and relieve the oxidative stress via PI3K/Akt/NOX4 signaling pathway.

AIM To explore the effects of praeruptorin A from Suhuang antitussive capsules on cough variant asthma(CVA).METHODS The rats were randomly divided into the normal group,the model group,the dexamethasone group(0.5 mg/kg),the Suhuang antitussive capsules group(7 g/kg)and the low,medium and high dose praeruptorin A groups(15,30 and 60 mg/kg).The rat model of CVA was established by intraperitoneal injection of sensitizer(1 mg/mL ovalbumin and 10 mg/mL aluminum hydroxide)and aerosol inhalation of 1%ovalbumin followed by the corresponding dosing of drugs by gavage initiated on the 14th day.Another 14 days later,the rats had their pathological pulmonary changes observed by HE,Masson and PAS stainings;their number of inflammatory cells in bronchoalveolar lavage fluid(BALF)detected by hematology analyzer;and their levels of IL-4,IL-5,IL-13 and MUC5AC in BALF detected by ELISA.The RAW264.7 cell inflammatory model induced by lipopolysaccharide(LPS)was treated with 4,8,16 μmol/L praeruptorin A or 0.25 mg/mL Suhuang antitussive capsules,respectively.And the cells had their NO level detected by Griess method,and their ROS expression observed using fluorescence microscopy.The detections of the pulmonary and cellular mRNA expressions of IL-6,IL-1β,COX-2,iNOS and PPAR-γ by RT-qPCR;and the protein expressions of p-P65,P65,p-IκBα,IκBα,NLRP3,caspase-1(p20)and IL-1β by Western blot were conducted in both the cells and the rats.RESULTS The in vivo result showed that praeruptorin A reduced the cough frequency(P＜0.01);prolonged the cough latency(P＜0.05,P＜0.01);reduced the number of eosinophils and neutrophils in BALF(P＜0.05,P＜0.01);decreased the levels of IL-4,IL-5,IL-13 and MUC5AC in BALF and the pulmonary mRNA expressions of IL-6,IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);and decreased the phosphorylation of P65 and IκBα protein and NLRP3,caspase-1(p20)and IL-1β protein expressions(P＜0.05,P＜0.01)as well.The in vitro result showed that praeruptorin A inhibited the release of LPS-induced NO and reduce the ROS level(P＜0.01);decreased the mRNA expressions of IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);increased PPAR-γ mRNA expression(P＜0.05),and decreased the phosphorylation of P65 and IκBα protein and the expression of NLRP3 protein(P＜0.05,P＜0.01).CONCLUSION Praeruptorin A,one of the main antitussive components of Suhuang antitussive capsules,may improve CVA because of its anti-inflammatory and antitussive role by inhibiting the activation of NF-κB signaling pathway and reducing the expression of NLRP3 inflammatory corpuscles.

The purpose of the present study was to investigate the effect of glutamate scavenger oxaloacetate (OA) combined with CGS21680, an adenosine A2A receptor (A2AR) agonist, on acute traumatic brain injury (TBI), and to elucidate the underlying mechanisms. C57BL/6J mice were subjected to moderate-level TBI by controlled cortical impact, and then were treated with OA, CGS21680, or OA combined with CGS21680 at acute stage of TBI. At 24 h post TBI, neurological severity score, brain water content, glutamate concentration in cerebrospinal fluid (CSF), mRNA and protein levels of IL-1β and TNF-α, mRNA level and activity of glutamate oxaloacetate aminotransferase (GOT), and ATP level of brain tissue were detected. The results showed that neurological deficit, brain water content, glutamate concentration in CSF, and the inflammatory cytokine IL-1β and TNF-α production were exacerbated in CGS21680 treated mice. Administrating OA suppressed the rise of both glutamate concentration in CSF and brain water content, and elevated the ATP level of cerebral tissue. More interestingly, neurological deficit, brain edema, glutamate concentration, IL-1β and TNF-α levels were ameliorated significantly in mice treated with OA combined with CGS21680. The combined treatment exhibited better therapeutic effects than single OA treatment. We also observed that GOT activity was enhanced in single CGS21680 treatment group, and both the GOT mRNA level and GOT activity were up-regulated in early-stage combined treatment group. These results suggest that A2AR can improve the efficiency of GOT and potentiate the ability of OA to metabolize glutamate. This may be the mechanism that A2AR activation in combination group augmented the neuroprotective effect of OA rather than aggravated the brain damages. Taken together, the present study provides a new insight for the clinical treatment of TBI with A2AR agonists and OA.
Adenosine A2 Receptor Agonists/therapeutic use* ; Adenosine Triphosphate ; Animals ; Brain Injuries/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Glutamic Acid ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/therapeutic use* ; Oxaloacetic Acid/therapeutic use* ; RNA, Messenger ; Receptor, Adenosine A2A/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Water

The Wandaitang，recorded in an ancient medical book named Fu Qingzhu's Obstetrics and Gynecology，is one of the Classical Prescriptions. The detailed discussion and record on Wantaitang by later medical scholars can be also regarded as the inheritance and development of the original academic thought from Fu Qingzhu's Obstetrics and Gynecology. By referring to recent literatures，we have found that there are a few reports on Wandaitang from the perspective of ancient literature，but such reports are not systematic or comprehensive enough. Under the premise of inheriting but not rigidly adhering to the ancients，investigation and analysis would be made in this paper from the aspects of the origin，efficacy，dose conversion between ancient and modern uses，usage and dosage form，modern clinical application，contraindications and others based on ancient and modern literatures，in order to further promote the textual research work on Wandaitang and provide reference for its secondary research and development. The research results showed that the origin of Wandaitang can be traced back to the Bianzhenglu（Collecting Record of Differentiation of Symptoms and Signs），and its effect can be summarized as invigorating Qi and spleen，soothing liver-Qi stagnation，elevating yang and arresting leucorrhoea. In view of the great difference between the dose of the original prescription of Wandaitang and the recommended dose in the pharmacopoeia，the author recommended that the clinical dosage of Wandaitang should be 30 g Atractylodis Macrocephalae Rhizoma，30 g Dioscoreae Rhizoma，6 g Ginseng Radix et Rhizoma，15 g Paeoniae Radix Alba，10 g Plantaginis Semen，10 g Atractylodis Rhizoma，3 g Glycyrrhizae Radix et Rhizoma，3 g Citri Reticulatae Pericarpium，3 g Schizonepetae Spica Carbonisata，and 3 g Bupleuri Radix. The main indications included leucorrhea，vulva pruritus，diarrhea，stranguria，anorexia，eczema，vertigo and so on. This prescription should be used with caution in pregnant women or those with excessive phlegm and dampness，Qi stagnation of spleen and stomach，or deficiency of Yin-fluid and blood. The research and development of Wandaitang compound preparation can be inclined to the direction of compound granules，to give full play to its clinical value and market value. The above studies，based on the textual research of ancient and modern literatures，are of great significance for clarifying the origin and clinical application of Wandaitang，and provide a new idea and basis for the secondary development of Wandaitang.

Objective: This study was performed to evaluate the efficacy of metformin on liver fat content (LFC) in first episode schizophrenia patients with olanzapine-induced weight gain, and the relationship between the change of LFC and the other metabolic indices. Methods: In a double-blind study, the clinically stable inpatients with first-episode schizophrenia under olanzapine monotherapy who gained more than 7% of their baseline weight were randomly assigned to two groups; one with olanzapine plus metformin (1,000 mg/day) (metformin group) and the other with olanzapine plus placebo (placebo group) for 16 weeks. All patients continued to maintain the original olanzapine dosage. LFC was measured by magnetic resonance imaging at baseline and at the end of 16 weeks, respectively. At the same time, glucose and lipid metabolism, homeostasis model assessment of insulin resistance index (HOMA-IR) were measured respectively, analyzing the correlation between the change value of LFC and other indicators. Results: Over the 16-week study period, LFC value in metformin group decreased compared with baseline. LFC change across the 16-week treatment period was −2.91% for the metformin group and 0.59% for the placebo group, with a between-group difference of −3.5% (95% confidence interval, −6.08 to −0.93; p = 0.009). Compared to baseline, in the metformin group, triglyceride and HOMA-IR reduced significantly, while high density lipoprotein cholesterol increased significantly at weeks 16. There was positive correlation between LFC changes and triglycerides, HOMA-IR changes significantly. Conclusion Metformin can significantly attenuate LFC in schizophrenia patients with olanzapine-induced weight gain. It may be related to the improvement of the part of the glucolipid metabolic indices.

Objective To investigate the clinical application of enteroscopies in China, and to further provide evidence for popularization and promotion of enteroscopies. Methods The survey was designed between January 1st , 2017 and July 31th , 2017 with pre-survey in Guangdong Province between May 1st , 2017 and July 31st , 2017. It was conducted in Chinese mainland between August 30th , 2017 and December 30th , 2017. Data were collected through the online survey and reality survey at 385 hospitals. A total of 373 hospitals gave feedbacks and 7 hospitals were unqualified for further analysis after data checking, so 366 hospitals were included for final analysis, with a responding rate of 95. 1％. Information on practice status of hospitals with enteroscopies and enteroscopists were collected. The chi-squared test was used for comparison of data between eastern and central and western regions. Results The hospitals owning enteroscopies accounted for 47. 0％ ( 172/366 ) , 154/172 ( 89. 5％) were tertiary referral hospitals, 112/172 ( 65. 1％) established enteroscopy units, and 84/172 ( 48. 8％) owned X-ray exclusive for enteroscopy. The proportion of enteroscopists with senior title was 40. 3％ (50/124), female enteroscopists accounted for 42. 7％ ( 53/124 ) . Most enteroscopists aged 31-40 ( 50. 8％) and 41-50 years ( 27. 4％) . 43. 0％ ( 74/172) hospitals employed only 1-2 enteroscopists. The diagnostic cases per year were less than 50 cases in 51. 2％ hospitals ( 88/172) . The therapeutic cases per year were less than 10 cases in 51. 7％hospitals ( 89/172 ) . Nineteen of 124 ( 15. 3％) of enteroscopists didn' t receive standard training. The number of hospitals performing enteroscopies in eastern regions was higher than that in central and western regions [111(51. 6％) VS 61(40. 4％), P=0. 034]. The training background of enteroscopists in eastern regions was better than that in central and western regions. Untrained endoscopists accounted for 10. 5％ in eastern regions, while those accounted for 22. 9％ in central and western regions with significant difference ( P=0. 031 ) . Conclusion Low number of patients treated and shortage of enteroscopists are obvious in Chinese mainland, especially in central and western regions. Standard training of enteroscopists is impending.

PURPOSE: Obstructive ileocolitis is an ulcero-inflammatory condition which typically occurs in the ileum or colon proximal to an obstructing colorectal lesion. If left unresolved, it often leads to intestinal perforation. We present a matched case control study of patients with obstructive ileocolitis caused by colorectal cancer to determine if any factors can predict this condition. METHODS: This is a retrospective review of 21 patients with obstructive colorectal cancer and histologically proven obstructive ileocolitis from 2005 to 2015 matched for age and sex with 21 controls with obstructing colorectal cancer without obstructive ileocolitis. RESULTS: The 21 patients with obstructive ileocolitis had a median age of 71 years (range, 52–86 years). The most common presenting symptom was abdominal pain (n = 16, 76.2%), followed by vomiting/nausea (n = 14, 66.7%) and abdominal distension (n = 12, 57.1%). Interestingly, the radiological feature of pneumatosis intestinalis was noted in only 1 case. No significant differences were observed in baseline comorbidities, clinical presentations, or tumor characteristics between the 2 groups. Patients with obstructive ileocolitis were found to have a significantly higher total leucocyte count (17.1 ± 9.4×109/L vs. 12.0 ± 6.8×109/L, P = 0.016), lower pCO2 (32.3 ± 8.2 mmHg vs. 34.8 ± 4.9 mmHg, P = 0.013), lower HCO3 (18.8 ± 4.5 mmol/L vs. 23.6 ± 2.7 mmol/L, P < 0.001), lower base excess (-6.53 ± 5.32 mmol/L vs. -0.57 ± 2.99 mmol/L, P < 0.001) and higher serum lactate levels (3.14 ± 2.19 mmol/L vs. 1.19 ± 0.91 mmol/L, P = 0.007) compared to controls. No radiological features were predictive of obstructive ileocolitis. CONCLUSION: Patients with obstructive ileocolitis tend to present with metabolic acidosis with respiratory compensation, raised lactate, and worse leucocytosis. Radiological features are not useful for predicting this condition.
Abdominal Pain ; Acidosis ; Case-Control Studies* ; Colon ; Colorectal Neoplasms* ; Comorbidity ; Compensation and Redress ; Crohn Disease* ; Humans ; Ileum ; Intestinal Obstruction ; Intestinal Perforation ; Lactic Acid ; Retrospective Studies

Chorismate synthase(CS, EC:4.2.3.5) catalyses 5-enolpyruvy-shikimate-3-phosphate to form chorismate, which is the essential enzyme for chorismate biosynthesis in organisms. The amino acid sequences of CS from 79 species of higher plants were reported in GenBank at present. 125 amino acid sequences of CS from Baphicacanthus cusia and other 78 species of plants were predicted and analyzed by using various bioinformatics software, including the composition of amino acid sequences, signal peptide, leader peptide, hydrophobic/hydrophilic, transmembrane structure, coiled-coil domain, protein secondary structure, tertiary structure and functional domains. The phylogenetic tree of CS protein family was constructed and divided into eight groups by phylogenetic analysis. The homology comparison indicated that B. cusia shared a high homology with several plants such as Sesamum indicum, Nicotiana tabacum, Solanum tuberosum and so on. The open reading frame(ORF) of all samples is about 1 300 bp, the molecular weight is about 50 kDa, the isoelectric point(pI) is 5.0-8.0 which illustrated that CS protein is slightly basic. The ORF of CS we cloned in B. cusia is 1 326 bp, the amino acid residues are 442, the molecular weight is 47 kDa and pI is 8.11. The CS in B.cusia showed obvious hydrophobicity area and hydrophilicity area, no signal peptide, and may exists transmembrane structure areas. The main secondary structures of CS protein are random coil and Alpha helix, also contain three main structural domains which are an active structural domain, a PLN02754 conserved domain and a FMN binding site. The acquired information in this study would provide certain scientific basis for further study on structure-activity relationship and structure modification of CS in plants in the future.
Acanthaceae ; enzymology ; Amino Acid Sequence ; Computational Biology ; Phosphorus-Oxygen Lyases ; chemistry ; Phylogeny ; Plant Proteins ; chemistry ; Protein Structure, Secondary

Fourteen compounds, including rubiprasin D (1), rubiprasin B (2), rubiprasin C (3), oleanolic acid (4), methyl-5-hydroxy-dinaphtho[1, 2-2'3']furan-7, 12-dione-6-carboxylate (5), rubioncolin C (6), mollugin (7), furomollugin (8), 3-amino-2-methoxycarbonyl-1, 4-naphthoquinone (9), 1-hydroxy-2-methyl-9, 10-anthraquinone (10), 2-hydroxy-6-methyl-9, 10-anthraquinone (11), 1, 4-dihydroxy-2-hydroxymethyl-9, 10-anthraquinone (12), 2-hydroxy-1-methoxy-9, 10-anthraquinone (13), and 1-hydroxy-2-methoxy-6-methyl-9, 10-anthraquinone(14), were isolated from the methanol extract of the roots and rhizomes of Rubia oncotricha using various column chromatographies. Their structures were mainly determined on basis of NMR and MS spectroscopic data analyses. Among them, 1 is a new oleanane triterpene, and compounds 2-5, 9 and 11-13 were obtained from this plant for the first time. Cytotoxic and nematicidal activities of all these compounds were evaluated, and the results showed that only 4, 6, 11 and 12 exhibited cytotoxicities against A549, SGC-7901 and HeLa cancer cell lines. The IC₅₀ of 6 were 19.42, 2.74, 8.07 μmol·L⁻¹, respectively.
Molecular Structure ; Naphthoquinones ; Plant Extracts ; Plant Roots ; Rhizome ; Rubia