Publications by authors named "Kailong Wang"

11 Publications

  • Page 1 of 1

Clinicopathological features, risk factors, and outcomes of immunoglobulin A nephropathy associated with hepatitis B virus infection.

J Nephrol 2021 Mar 8. Epub 2021 Mar 8.

Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, People's Republic of China.

Background: Hepatitis B virus (HBV) infections are associated with an increased risk of kidney diseases. However, the effects of HBV infection on the prognosis of immunoglobulin A nephropathy (IgAN) are unclear.

Methods: A total of 838 patients with biopsy-confirmed IgAN were enrolled in this retrospective cohort study. The patients were categorized into either affected by IgAN and HBV infection (HBsAg-IgAN) or by primary IgAN with no sign of HBV infection (P-IgAN). A 1:1 propensity-score matching was performed between the two groups, followed by a Kaplan-Meier survival analysis, to compare the prognoses, and a Cox regression analysis, to identify factors influencing the HBsAg-IgAN outcomes.

Results: A total of 176 pairs of patients were successfully matched. A significant difference in the systolic blood pressure and urea, serum creatinine, uric acid, and 24-h urine protein levels was observed between the groups. A renal pathological analysis also revealed a significant difference in the mesangial hypercellularity between the groups. During a median follow-up period of 2.4 years, Kaplan-Meier analysis also revealed a significant difference in the renal survival between the groups. Furthermore, multivariate Cox analysis confirmed that HBV infection is an independent risk factor for IgAN progression (hazard ratio [HR] 2.096; 95% confidence interval [CI] 1.091-4.026). Finally, the HBsAg-IgAN patients who received treatment with renin-angiotensin-aldosterone system inhibitors had a better overall prognosis than those who received immunosuppressive therapy and antiviral treatment.

Conclusion: Our results indicate that the clinicopathological features and outcomes of patients with IgAN differ significantly between those with and without HBV infection, and that HBV is an independent risk factor for IgAN progression.
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http://dx.doi.org/10.1007/s40620-021-01004-2DOI Listing
March 2021

HTBPI, an active phenanthroindolizidine alkaloid, inhibits liver tumorigenesis by targeting Akt.

FASEB J 2020 09 24;34(9):12255-12268. Epub 2020 Jul 24.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Akt, a crucial protein involved in a variety of signaling pathways in cancer, acts as an important regulator of survival in hepatocellular carcinoma (HCC), and provides curative option for the related drugs development. We have found an active phenanthroindolizidine alkaloid, (13aR,14R)-9,11,12,13,13a,14-hexahydro-3,6,7-trimethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-14-ol (HTBPI), is a promising Akt inhibitor effective in the suppression of HCC cells proliferation through stimulating apoptotic and autophagic capability in vivo and in vitro. Treatment of HTBPI combined with a classical autophagy-lysosomal inhibitor (bafilomycin A1), could enhance stimulation effects of apoptosis on HCC cell lines. In addition, we confirmed HTBPI targeting Akt, occupied the kinase binding domain (Thr 308) of Akt to inactivate its function by CETSA and DARTS assay. In contrast, ectopic Akt-induced overexpression significantly abrogated inhibitory effects of HTBPI on cell viability and proliferation. Furthermore, high p-Akt (Thr 308) expression is collated with liver tumor formation and poor survival in HCC patients. In conclusions, HTBPI impeded HCC progress through regulation of apoptosis and autophagy machinery via interaction with p-Akt (Thr 308). This may provide potential molecular candidate by targeting Akt for the therapy of HCC patients.
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http://dx.doi.org/10.1096/fj.202000254RDOI Listing
September 2020

Effect of Massage on the TLR4 Signalling Pathway in Rats with Neuropathic Pain.

Pain Res Manag 2020 16;2020:8309745. Epub 2020 Dec 16.

Department of Massage, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi 530000, China.

This study set out to investigate the effect of massage on the Toll-like receptor 4 (TLR4) signalling pathway in the dorsal root ganglia of rats that had undergone spinal nerve ligation (SNL), with the hypothesis that massage could be used as an analgesic. Forty female SD rats were randomly divided into 5 groups: the control group, sham-operated group, model group, sham massage group, and massage group. There were 8 rats in each group. SNL rat models were established in the model group, sham massage group, and massage group. Rats in the sham-operated group underwent surgery to expose the vertebral nerves, but no further procedures were performed. The control group consisted of intact animals. The rats in the massage group underwent massage using a massage simulation machine once a day for 14 d in succession; the hind limbs of the rats in the sham massage group were gently touched with a cloth bag once a day for 14 continuous days. The rats in the control group, the sham-operated group, and the model group did not receive any intervention and were observed for 14 d. Paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) of rats in each group were detected 1 d before modelling and at 1, 3, 7, and 14 d after modelling. Fourteen days after modelling, the expression levels of TLR4, IRAK1, TRAF6, TNF-, and IL-6 were detected in all rats. The PWTL and PWMT of SNL rats were decreased, while these parameters were elevated after massage. SNL rats showed higher levels of TLR4, IRAK1, TRAF6, IL-6, and TNF-, and massage effectively lowered the expression levels of these molecules. Inhibiting activation of the TLR4 signalling pathway, which can reduce the release of inflammatory factors, may be one mechanism by which massage treats neuropathic pain.
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http://dx.doi.org/10.1155/2020/8309745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759416PMC
March 2021

Anticancer activities of TCM and their active components against tumor metastasis.

Biomed Pharmacother 2021 Jan 11;133:111044. Epub 2020 Dec 11.

State Key Laboratory of Component-based Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address:

Traditional Chinese Medicine (TCM) has the characteristics of multiple targets, slight side effects and good therapeutic effects. Good anti-tumor effects are shown by Traditional Chinese Medicine prescription, Chinese patent medicine, single Traditional Chinese Medicine and Traditional Chinese medicine monomer compound. Clinically, TCM prolonged the survival time of patients and improved the life quality of patients, due to less side effects. Cancer metastasis is a complex process involving numerous steps, multiple genes and their products. During the process of tumor metastasis, firstly, cancer cell increases its proliferative capacity by reducing autophagy and apoptosis, and then the cancer cell capacity is stimulated by increasing the ability of tumors to absorb nutrients from the outside through angiogenesis. Both of the two steps can increase tumor migration and invasion. Finally, the purpose of tumor metastasis is achieved. By inhibiting autophagy and apoptosis of tumor cells, angiogenesis and EMT outside the tumor can inhibit the invasion and migration of cancer, and consequently achieve the purpose of inhibiting tumor metastasis. This review explores the research achievements of Traditional Chinese Medicine on breast cancer, lung cancer, hepatic carcinoma, colorectal cancer, gastric cancer and other cancer metastasis in the past five years, summarizes the development direction of TCM on cancer metastasis research in the past five years and makes a prospect for the future.
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http://dx.doi.org/10.1016/j.biopha.2020.111044DOI Listing
January 2021

IRF1-mediated downregulation of PGC1α contributes to cardiorenal syndrome type 4.

Nat Commun 2020 09 16;11(1):4664. Epub 2020 Sep 16.

Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), 400037, Chongqing, China.

Cardiorenal syndrome type 4 (CRS4) is a common complication of chronic kidney disease (CKD), but the pathogenic mechanisms remain elusive. Here we report that morphological and functional changes in myocardial mitochondria are observed in CKD mice, especially decreases in oxidative phosphorylation and fatty acid metabolism. High phosphate (HP), a hallmark of CKD, contributes to myocardial energy metabolism dysfunction by downregulating peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α). Furthermore, the transcriptional factor interferon regulatory factor 1 (IRF1) is revealed as the key molecule upregulated by HP through histone H3K9 acetylation, and responsible for the HP-mediated transcriptional inhibition of PGC1α by directly binding to its promoter region. Conversely, restoration of PGC1α expression or genetic knockdown of IRF1 significantly attenuates HP-induced alterations in vitro and in vivo. These findings demonstrate that IRF1-PGC1α axis-mediated myocardial energy metabolism remodeling plays a crucial role in the pathogenesis of CRS4.
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http://dx.doi.org/10.1038/s41467-020-18519-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494935PMC
September 2020

Cellular senescence and cancer: Focusing on traditional Chinese medicine and natural products.

Cell Prolif 2020 Oct 3;53(10):e12894. Epub 2020 Sep 3.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Cancer is the principal cause of death and a dominant public health problem which seriously threatening human life. Among various ways to treat cancer, traditional Chinese medicine (TCM) and natural products have outstanding anti-cancer effects with their unique advantages of high efficiency and minimal side effects. Cell senescence is a physiological process of cell growth stagnation triggered by stress, which is an important line of defence against tumour development. In recent years, active ingredients of TCM and natural products, as an interesting research hotspot, can induce cell senescence to suppress the occurrence and development of tumours, by inhibiting telomerase activity, triggering DNA damage, inducing SASP, and activating or inactivating oncogenes. In this paper, the recent research progress on the main compounds derived from TCM and natural products that play anti-cancer roles by inducing cell senescence is systematically reviewed, aiming to provide a reference for the clinical treatment of pro-senescent cancer.
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http://dx.doi.org/10.1111/cpr.12894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574878PMC
October 2020

Klotho is regulated by transcription factor Sp1 in renal tubular epithelial cells.

BMC Mol Cell Biol 2020 Jun 22;21(1):45. Epub 2020 Jun 22.

Department of Nephrology, the key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, People's Republic of China.

Background: Klotho is a multifunctional protein, which exists both in a membrane bound and a soluble form. In renal tubules, Klotho is involved in cell senescence, anti-oxidant response, and renal fibrosis, thus regulation of its expression is critical to understand its roles in renal diseases. Indeed, reduced expression was observed in various renal disease. However, the mechanisms underlying transcriptional regulation of the human klotho gene (KL) largely remain unknown.

Results: Here we demonstrated that the Klotho expression in human renal tubular epithelial cells (RTECs) was enhanced by overexpression of the transcription factor Sp1. On the contrary, Klotho expression was decreased by Sp1 knockdown. Besides, increased expression of Sp1 alleviated TGF-β1-induced fibrosis in HK-2 cells by inducing Klotho expression. Luciferase reporter assays and chromatin immunoprecipitation assays further identified the binding site of Sp1 was located in - 394 to - 289 nt of the KL promoter, which was further confirmed by mutation analysis.

Conclusions: These data demonstrate that KL is a transcriptional target of Sp1 and TGF-β1-induced fibrosis was alleviated by Sp1 in human RTECs by directly modulating Klotho expression, which help to further understand the transcriptional regulation of Klotho in renal disease models.
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http://dx.doi.org/10.1186/s12860-020-00292-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309980PMC
June 2020

IRF-1 promotes renal fibrosis by downregulation of Klotho.

FASEB J 2020 03 21;34(3):4415-4429. Epub 2020 Jan 21.

Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Although the key role of renal fibrosis in the progression of chronic kidney disease (CKD) is well known, the causes of renal fibrosis are not fully clarified. In this study, interferon regulatory factor 1 (IRF-1), a mammalian transcription factor, was highly expressed in fibrotic kidney of CKD patients. Concordantly, the expression level of IRF-1 was significantly elevated in the kidney of unilateral ureteral obstruction (UUO) and Adriamycin nephropathy (ADR) mice. In tubular epithelial cells, overexpression of IRF-1 could induce profibrotic markers expression, which accompanied by dramatic downregulation of Klotho, an important inhibitor of renal fibrosis. Luciferase reporter analysis and ChIP assay revealed that IRF-1 repressed Klotho expression by downregulation of C/EBP-β, which regulates Klotho gene transcription via directly binding to its promoter. Further investigation showed that tumor necrosis factor-alpha may be an important inducement for the increase of IRF-1 in tubular epithelial cells after UUO and genetic deletion of IRF-1 attenuated renal fibrosis in UUO mice. Hence, these findings demonstrate that IRF-1 contributes to the pathogenesis of renal fibrosis by downregulation of Klotho, and suppresses IRF-1 may be a potential therapeutic target for CKD.
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http://dx.doi.org/10.1096/fj.201902446RDOI Listing
March 2020

Alkaloids from Traditional Chinese Medicine against hepatocellular carcinoma.

Biomed Pharmacother 2019 Dec 23;120:109543. Epub 2019 Oct 23.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address:

Hepatocellular carcinoma (HCC) has become one of the major diseases that are threatening human health in the 21st century. Currently there are many approaches to treat liver cancer, but each has its own advantages and disadvantages. Among various methods of treating liver cancer, natural medicine treatment has achieved promising results because of their superiorities of high efficiency and availability, as well as low side effects. Alkaloids, as a class of natural ingredients derived from traditional Chinese medicines, have previously been shown to exert prominent anti-hepatocarcinogenic effects, through various mechanisms including inhibition of proliferation, metastasis and angiogenesis, changing cell morphology, promoting apoptosis and autophagy, triggering cell cycle arrest, regulating various cancer-related genes as well as pathways and so on. As a consequence, alkaloids suppress the development and progression of liver cancer. In this study, the mechanisms of representative alkaloids against hepatocarcinoma in each class are described systematically according to the structure classification, which mainly divides alkaloids into piperidine alkaloids, isoquinoline alkaloids, indole alkaloids, terpenoids alkaloids, steroidal alkaloids and other alkaloids. Besides using them alone, synergistic effects created together with other chemotherapy drugs and some special preparation methods also have been demonstrated. In this review, we have summarized the potential roles of several common alkaloids in the prevention and treatment of HCC, by revising the preclinical studies, highlighting the potential applications of alkaloids when they function as a therapeutic choice for HCC treatment, and integrating them into clinical practices.
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http://dx.doi.org/10.1016/j.biopha.2019.109543DOI Listing
December 2019

Sophoridine Inhibits Human Colorectal Cancer Progression via Targeting MAPKAPK2.

Mol Cancer Res 2019 12 1;17(12):2469-2479. Epub 2019 Oct 1.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

is a traditional Chinese medicine commonly used to treat cancer in China. However, its active components and underlying mechanism remain ambiguous. In this study, we have screened the pharmacokinetic parameters of the main chemical constituents of by Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform and have found that Sophoridine is one of the best antitumor active ingredients. We have found that MAPKAPK2 is a potential target for Sophoridine by the PharmMapper and KEGG databXase analysis. Moreover, we have found that Sophoridine selectively inactivates phospho-MAPKAPK2 (Thr222) and directly binds into the ATP site of MAPKAPK2 by molecular docking. Furthermore, we have found out a direct binding between MAPKAPK2 and Sophoridine by cellular thermal shift assay and drug affinity responsive targets stability assay. The inhibition effects are further confirmed by Western blot: Sophoridine significantly decreases phospho-MAPKAPK2 (Thr222) in a time-dependent manner, but there is no obvious change in its total expression in colorectal cancer cells. Clinical studies have shown that a higher level of MAPKAPK2 is associated with a poorer percent survival rate (prognosis). Furthermore, a higher level of MAPKAPK2 is positively associated with the enrichment of downregulation of apoptosis and autophagy by gene set enrichment analysis, as well as upregulation of proliferation and cell-cycle arrest. Taken together, our results suggest that the MAPKAPK2 plays a key role in Sophoridine-inhibited growth and invasion in colorectal cancers. IMPLICATIONS: These studies show that Sophoridine may be a promising therapeutic strategy that blocks tumorigenesis in colorectal cancers.
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http://dx.doi.org/10.1158/1541-7786.MCR-19-0553DOI Listing
December 2019

[The design and application of a moxibustion instrument with less harmful smoke and direction adjustment].

Zhongguo Zhen Jiu 2018 Feb;38(2):217-21

Tuina Department, the First Affiliated Hospital of Guangxi University of CM, Nanning 530023, China.

The design of a clip-on moxibustion instrument which could adjust the directions and absorb harmful granules of moxa smoke was introduced in this paper. It was designed to solve the problems in home health care and clinical treatment, such as the inconvenience of adjustment of moxibustion directions and temperature, more dust and granules of moxa smoke and inconvenience of moxibustion placement. The main part of moxibustion instrument was made up of moxibustion box, bracket and base clamp. The moxibustion box could fix moxa stick and absorb smoke granules; the bracket could be twisted to adjust the direction of moxibustion box; the base clamp was aimed to fix moxibustion box on the edge of the object to save space. This moxibustion instrument could be used for various indications of moxibustion, especially in the joints or body parts with less muscles; and it can significantly enhance the pertinence and safety of moxibustion, and reduce the labor intensity. This moxibustion instrument is original and unique, simple and reasonable, easy to operate, with low cost and good effect, which will increase new vitality for the popularization and development of moxibustion.
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http://dx.doi.org/10.13703/j.0255-2930.2018.02.030DOI Listing
February 2018