Publications by authors named "Zhengkun Hou"

10 Publications

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Quercetin alleviates chronic renal failure by targeting the PI3k/Akt pathway.

Bioengineered 2021 12;12(1):6538-6558

Division of Nephrology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong, Guangzhou, China.

Chronic renal failure (CRF) threatens human health greatly and attracts worldwide concerns of health professionals in the public health sector. In our preliminary study, we found that Compound capsule (Shengqing Jiangzhuo Capsule, SQJZJN) had a significant therapeutic effect on CRF. Quercetin is one of the main components of this Compound capsule. In this study, we investigated the effect of Quercetin monomer on CRF and the regulation of PI3k/Akt pathway. Network pharmacology analysis methods were employed to analyze the SQJZJN/Quercetin/PIK3R1 network relationships. In this study, a CRF rat model was prepared using the gavage adenine solution method and detected the indicators of Creatinine (Cr), Blood Urea Nitrogen (BUN), and Uric Acid (UA). After treating the rat model with Quercetin and PIK3R1-interfering lentivirus, respectively, we observed the changes on the histological morphology of the kidney and detected apoptosis using TUNEL staining. Gene and protein expression associated with renal function were detected using qPCR, WB and immunofluorescence. Quercetin was identified as the main ingredient of SQJZJN by the network pharmacological screening and Quercetin at 1.5 and 3 g/(kg.d) concentrations could effectively alleviate the CRF symptoms, reduce the levels of Cr, BUN, and UA, and markedly inhibit cell apoptosis demonstrated by the intragastric administration. Furthermore, the protein expression of p-PI3K, p-AKT, NLRP3, caspase1, AQP1, and AQP2 in all groups was detected by immunofluorescence and western blot assays, indicating that Quercetin could reduce the expression of NLRP3, caspase1, p-PI3k, and p-Akt, and increase the expression of AQP1 and AQP2 in the renal tissues of CRF rats. Being labeled with biotin and incubated with the total protein extracted from kidney tissues, Quercetin could bind to PIK3R1. Following the PIK3R1 interference lentivirus was injected into the CRF model rats by tail vein, the CRF symptoms were effectively alleviated in the PIK3R1 interference group, consistent with the effect of Quercetin. Taken together, Quercetin, a major component of SQJZJN, might minimize renal fibrosis and apoptosis in CRF rats by inhibiting the PI3k/Akt pathway through targeting PIK3R1. By regulating AQP1 and AQP2, both water retention and toxin accumulation were reduced.
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December 2021

Scientometric Analysis of Medicinal and Edible Plant .

Front Pharmacol 2021 12;12:725162. Epub 2021 Aug 12.

Postgraduate College, Guangzhou University of Chinese Medicine, Guangzhou, China.

A scientometric analysis to obtain knowledge mapping of revealed the current research situation, knowledge base and research hotspots in research. -related documents published from 1987 to 2020 were selected through the Web of Science Core Collection. CiteSpace, VOSviewer and Microsoft Excel were used to construct knowledge maps of the research field. A total of 367 documents and their references were analyzed. These papers were primarily published in mainland China (214), followed by Japan (57) and South Korea (52), and they each formed respective cooperation networks. The document co-citation analysis suggested that the identification of Salisb. species, the production of alkaloids, and the mechanisms of action of these alkaloids formed the knowledge bases in this field. A keyword analysis further revealed that the research hotspots were primarily concentrated in three fields of research involving berberine, Franch, and (Thunb) Makino. Oxidative stress, rat plasma (for the determination of plasma alkaloid contents), and Alzheimer's disease are recent research hotspots associated with . research was mainly distributed in three countries: China, Japan, and South Korea. Researchers were concerned with the identification of species, the production of alkaloids, and the efficacy and pharmacological mechanism of the constituent alkaloids. In addition, the anti-oxidative stress, pharmacokinetics, and Alzheimer's disease treatment of are new hotspots in this field. This study provides a reference for researchers.
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August 2021

Quantifying Liver-Stomach Disharmony Pattern of Functional Dyspepsia Using Multidimensional Analysis Methods.

Evid Based Complement Alternat Med 2020 10;2020:2562080. Epub 2020 Oct 10.

Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China.

Purpose: This study aims to develop and validate a quantitative model for measuring severity of a typical traditional Chinese medicine (TCM) pattern for functional dyspepsia (FD) using multidimensional analysis methods including confirmatory factor analysis (CFA) and multidimensional item response theory (MIRT).

Methods: A scale and theoretical models were constructed according to the definition of pathogenesis about "liver-stomach disharmony" patterns of FD. With data collected from 502 patients in a cross-section study, the theoretical model was validated with CFA, and the related validity and reliability were evaluated in Amos 21.0. By the use of the MIRT paradigm, psychometric properties of the scale were estimated and evaluated for pattern quantification.

Results: A scale consisting of 12 items was constructed detecting three latent traits of the pattern. The theoretical model was evaluated to be with adequate consistency with clinical data as RMSEA < 0.05, CFI = 0.94, and /D = 2.29. As the correlation between symptoms and related pattern factors evaluated to be with adequate factor loading, the instrument is of preliminary interpretation. Most precision of assessment could be achieved for patients with moderate severity of the pattern as shown in test information and standard error functions.

Conclusions: An instrument with an interpretable conceptual framework was developed for pattern quantification in TCM clinical practice. By constructing and evaluating both psychological and physical effects in a multidimensional model of the TCM pattern of FD, the paradigm raised in this article provided a valuable reference for interpreting complex diseases and theories such as FD and TCM patterns.
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October 2020

A Methodological and Reporting Quality Assessment of Systematic Reviews/Meta-Analyses about Chinese Medical Treatment for Gastroesophageal Reflux Disease.

Gastroenterol Res Pract 2020 24;2020:3868057. Epub 2020 Sep 24.

Gastroenterology Department, The First Affiliated Hospital, of Guangzhou University of Chinese Medicine, Guangzhou Guangdong, China.

Objective: To access the methodological and reporting quality of systematic reviews (SRs)/meta-analyses (MAs) about Chinese medical treatment for gastroesophageal reflux disease (GERD).

Methods: The PubMed, Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical (CBM), Web of Science, and Cochrane Library databases were searched from inception to June 2020. Two researchers independently screened the literature considering the eligibility criteria. Overview Quality Assessment Questionnaire (OQAQ), Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to assess the methodological and reporting quality of the included reports. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the level of evidence in each report.

Results: Thirty-three SRs/MAs met the inclusion criteria. The OQAQ results showed that defects in the methodological quality of 17/32 reports were major, with scores of 3 points. Analyzing a single item as the object, search strategies (item 2), and risk of bias in individual studies (item 4) was considered poor. The AMSTAR 2 results showed that 25.4% of the items were not reported, and 7.8% of the items were only partially reported. The overall assessment of AMSTAR 2 showed the majority of systematic reviews and meta-analyses were of low/very low (31/33, 93.9%) methodological quality, with a lack of protocol registration and excluded study list. The PRISMA results showed that 19.9% of items were not reported, and 15.2% of items were only partially reported, due to a lack of protocol registration and study selection methods. The methodological and reporting quality of the included studies was generally poor. Evidence evaluation with GRADE showed that most (31/33) of the included studies had low or very low levels of evidence.

Conclusion: The methodological and reporting quality of SRs/MAs about Chinese medical treatment for GERD is generally poor. The main problems included incomplete search strategies, risk of bias in individual studies, the lack of protocol registration and excluded study list, and incorrect study selection methods.
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September 2020

MicroRNA-200a Targets Cannabinoid Receptor 1 and Serotonin Transporter to Increase Visceral Hyperalgesia in Diarrhea-predominant Irritable Bowel Syndrome Rats.

J Neurogastroenterol Motil 2018 Oct;24(4):656-668

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Background/aims: MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown.

Methods: We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats.

Results: The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs.

Conclusions: This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.
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October 2018

Quantifying Liver Stagnation Spleen Deficiency Pattern for Diarrhea Predominate Irritable Bowel Syndromes Using Multidimensional Analysis Methods.

Evid Based Complement Alternat Med 2018 12;2018:6467135. Epub 2018 Feb 12.

The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Objective: This study aims to offer a new approach for quantifying severity of traditional Chinese medicine pattern with multidimensional analysis methods.

Methods: A scale and theoretical models were constructed based on the definition of liver stagnation spleen deficiency pattern. Clinical data of 344 IBS-D patients from a cross-sectional study was used for feature validation of the model. Confirmatory factor analysis was used for evaluating the models. Also, multidimensional item response model was used for assessing multidimensional psychometric properties of the scale.

Results: Detecting two latent traits, the Cronbach's alpha of the 9-item scale was 0.745. Multidimensional model was evaluated with significant goodness of fit indices while the unidimensional model was rejected. The multidimensional item response model showed all the items had adequate discrimination. Parameters presented adequate explanation regarding mental syndromes having high factor loading on the liver stagnation factor and abdominal discomfort syndromes highly related to the spleen deficiency factor. Test information function showed that scale demonstrated the highest discrimination power among patients with moderate to high level of severity.

Conclusions: The application of the multidimensional analysis methods on the basis of theoretical model construction provides a useful and rational approach for quantifying the severity of traditional Chinese medicine patterns.
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February 2018

MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1.

Cell Physiol Biochem 2017 14;44(6):2256-2268. Epub 2017 Dec 14.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Background/aims: Irritable bowel syndrome with diarrhoea (IBS-D) is a chronic, functional bowel disorder characterized by abdominal pain or diarrhoea and altered bowel habits, which correlate with intestinal hyperpermeability. MicroRNAs (miRNAs) are involved in regulating intestinal permeability in IBS-D. However, the role of miRNAs in regulating intestinal permeability and protecting the epithelial barrier remains unclear. Our goals were to (i) identify differential expression of miRNAs and their targets in the distal colon of IBS-D rats; (ii) verify in vitro whether occludin (OCLN) and zonula occludens 1 (ZO1/TJP1) were direct targets of miR-144 and were down-regulated in IBS-D rats; and (iii) determine whether down-regulation of miR-144 in vitro could reverse the pathological hallmarks of intestinal hyperpermeability via targeting OCLN and ZO1.

Methods: The IBS-D rat model was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. The distal colon was obtained in order to perform miRNA microarray analysis and to isolate and culture colonic epithelial cells. When differential expression of miRNA was found, the results were verified by qRT-PCR, and the target genes were further explored by bioinformatics analysis. Correlation analyses were carried out to compare the expression of miRNA and target genes. Then, mutants, miRNA mimics and inhibitors of the target genes were constructed and transfected to colonic epithelial cells. qRT-PCR, western blotting, enzyme-linked immunosorbent assays (ELISAs) and dual-luciferase assays were used to investigate the expression of miR-144 and OCLN, ZO1 in IBS-D rats.

Results: There were 8 up-regulated and 18 down-regulated miRNAs identified in the IBS-D rat model. Of these, miR-144 was markedly up-regulated and resulted in the down-regulation of OCLN and ZO1 expression. Overexpression of miR-144 by transfection of miR-144 precursor markedly inhibited the expression of OCLN and ZO1. Further studies confirmed that OCLN and ZO1 were direct targets of miR-144. Additionally, intestinal hyperpermeability was enhanced by miR-144 up-regulation and attenuated by miR-144 down-regulation in IBS-D rat colonic epithelial cells. Moreover, rescue experiments showed that overexpression of OCLN and ZO1 significantly eliminated the inhibitory effect of miR-144, which showed a stronger effect on the attenuation of intestinal hyperpermeability.

Conclusion: Up-regulation of miR-144 could promote intestinal hyperpermeability and impair the protective effect of the epithelial barrier by directly targeting OCLN and ZO1. miR-144 is likely a key regulator of intestinal hyperpermeability and could be a potential therapeutic target for IBS-D.
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March 2018

Adalimumab for Moderately to Severely Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.

BioDrugs 2016 Jun;30(3):207-17

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Evidence-based studies are increasingly being focused on evaluating the efficacy and safety of adalimumab (ADA) for moderately to severely active ulcerative colitis (UC). However, the dosage pattern of ADA for UC management is still not clear.

Objective: A meta-analysis was conducted to evaluate the efficacy and safety of different ADA dosage regimens for moderately to severely active UC.

Methods: The Medline, EMBASE, ISI Web of Knowledge, and Cochrane databases were searched from their inception to January 2015. Randomized controlled trials (RCTs) comparing ADA with placebo were eligible for initial inclusion. The efficacy and side effects were evaluated for ADA 160/80 (ADA 160/80 mg at weeks 0/2 and then 40 mg at weeks 4 and 6), and ADA 80/40 (ADA 80/40 mg at weeks 0/2 and then 40 mg at weeks 4 and 6) induction therapy, with ADA 40 mg every other week (EOW) for maintenance therapy of 52 weeks. The pooled risk ratio (RR) and its 95 % confidence interval (CI) were calculated.

Results: Three RCTs were included. All of the studies were considered to have a low risk of bias. ADA 160/80 was more effective than placebo for induction of clinical remission (RR 1.62, 95 % CI 1.15-2.29), clinical response (RR 1.37, 95 % CI 1.19-1.59), mucosal healing (RR 1.27, 95 % CI 1.08-1.50), and inflammatory bowel disease questionnaire (IBDQ) response (RR 1.22, 95 % CI 1.05-1.43) and did not increase adverse events (RR 1.10, 95 % CI 0.95-1.27). Compared with placebo, ADA 80/40 did not show significant differences for induction of clinical remission and clinical response and did not increase adverse events. ADA 40 mg EOW was superior to placebo in maintaining clinical remission (RR 2.38, 95 % CI 1.57-3.59), clinical response (RR 1.69, 95 % CI 1.29-2.21), mucosal healing (RR 1.69, 95 % CI 1.26-2.28), and IBDQ response (RR 1.73, 95 % CI 1.28-2.34). Compared with placebo, ADA 40 mg EOW increased adverse events (RR 1.28, 95 % CI 1.06-1.54).

Conclusion: ADA 160/80 was a safe and effective treatment for induction management of moderately to severely active UC, but the benefits of ADA 80/40 application were limited. ADA 40 mg EOW was effective for maintenance management of UC. Additional well designed RCTs are needed to confirm these results.
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June 2016

MiR-29a promotes intestinal epithelial apoptosis in ulcerative colitis by down-regulating Mcl-1.

Int J Clin Exp Pathol 2014 1;7(12):8542-52. Epub 2014 Dec 1.

First School of Clinic Medicine & First Affiliated Hospital of Guangzhou University of Chinese Medicine China.

Objective: While it's widely accepted that the etiology of ulcerative colitis (UC) involves both genetic and environmental factors, the pathogenesis of ulcerative colitis is still poorly understood. Intestinal epithelial apoptosis is one of the most common histopathological changes of UC and the expression of a number of apoptosis genes may contribute to the progression of UC. MicroRNAs have recently emerged as powerful regulators of diverse cellular processes and have been shown to be involved in many immune-mediated disorders such as psoriasis, rheumatoid arthritis, lupus, and asthma. A unique microRNA expression profile has been identified in UC, suggesting that, microRNAs play an important role in the pathogenesis of UC. We investigated the role of miR-29a in intestinal epithelial apoptosis in UC.

Methods: The expression of miR-29a and Mcl-1, an anti-apoptotic BCL-2 family member, was evaluated in both UC patients and UC mice model induced by dextran sodium sulfate (DSS). The apoptosis rate of intestinal epithelial cells was also evaluated.

Results: In UC patients and DSS-induced UC in mice, the expression of miR-29a and Mcl-1, were up-regulated and down-regulated, respectively. We identified a miR-29a binding site (7 nucleotides) on the 3'UTR of mcl-1 and mutation in this binding site on the 3'UTR of mcl-1 led to mis-match between miR-29a and mcl-1. Knockout of Mcl-1 caused apoptosis of the colonic epithelial HT29 cells. In addition, miR-29a regulated intestinal epithelial apoptosis by down-regulating the expression of Mcl-1.

Conclusion: miR-29a is involved in the pathogenesis of UC by regulating intestinal epithelial apoptosis via Mcl-1.
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October 2015

Treatment of constipation-predominant irritable bowel syndrome by focusing on the liver in terms of Traditional Chinese Medicine: a meta-analysis.

J Tradit Chin Med 2013 Oct;33(5):562-71

Objective: To assess the efficacy of Traditional Chinese Medicine (TCM) on constipation-predominant irritable bowel syndrome by focusing on the liver.

Methods: Databases (domestic and foreign) were searched with the key words "irritable bowel syndrome'", "constipation", and "Chinese medicine"; the relevant articles were retrieved and evaluated. Cure rate, "remarkable efficacy", recurrence rate and the incidence of adverse reactions were the outcome indicators. Review Manager ver 5.1 was used for this meta-analysis, and funnel plots used to deted publication bias.

Results: Nineteen randomized controlled trials were included and 1510 patients involved. The treatment guided byTCM based on the liver was superior to Western Medicine [odds ratio (OR) = 2.46, 95% confidence interval (CI) 1.80, 3.35)], cure rate [OR = 2.61, 95% Cl (1.93, 3.52)], remarkable efficacy [OR = 2.68, 95% Cl (1.82, 3.95)], recurrence rate [OR = 0.19, 95% CI (0.12, 0.29)] and the incidence of adverse reactions [OR = 0.24, 95% CI (0.09, 0.65)]. However, funnel plots showed publication bias.

Conclusion: Compared with Western Medicine, the treatment of IBS-C based on the liver is significantly better but the results must be treated with caution because publication bias was recorded.
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October 2013