Publications by authors named "Kanglin Guo"

3 Publications

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Tertiary lymphoid organs are associated with the progression of kidney damage and regulated by interleukin-17A.

Theranostics 2021 1;11(1):117-131. Epub 2021 Jan 1.

Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Tertiary lymphoid organs (TLOs) occur after multiple chronic kidney injuries. interleukin-17A (IL-17A) has been reported to associate with the development of TLOs in inflammatory diseases. However, regulation of the renal TLOs and its clinical significance to the pathogenesis of chronic kidney injury are unknown. To evaluate the clinical significance and regulation of renal TLOs, we analyzed the progression of patients with kidney damage based on the existence and absence of TLOs in a larger multicenter cohort. We also blocked the recruitment of lymphocyte cells into the kidney by FTY720 (fingolimod) . Besides, we used aged IL-17A genetic knocked out mice and IL-17A-neutralizing antibody to explore the role of IL-17A in renal TLOs formation. : We demonstrated that renal TLOs of IgA nephropathy patients were associated with disease severity and were independent risk factors for renal progression after adjustment for age, sex, mean arterial pressure, proteinuria and, baseline eGFR and MEST-C score, especially in the early stage. Plasma levels of TLO-related chemokines CXCL13, CCL19, and CCL21 were higher in patients with renal TLOs. Inhibiting the formation of renal TLOs by FTY720 could reduce the intrarenal inflammation and fibrosis, and early intervention was found to be more effective. IL-17A was increased in renal TLOs models, and genetic depletion of IL-17A or treatment with anti-IL-17A antibody resulted in a marked reduction of the TLOs formation as well as alleviation of renal inflammation and fibrosis. These results indicate that TLOs are associated with the progression of kidney damage and regulated by IL-17A and may be effective targets for the treatment of kidney damage.
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http://dx.doi.org/10.7150/thno.48624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681089PMC
August 2021

Zika virus circumvents host innate immunity by targeting the adaptor proteins MAVS and MITA.

FASEB J 2019 09 10;33(9):9929-9944. Epub 2019 Jun 10.

School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Recently, Zika virus (ZIKV) has generated extraordinary concern because of its severe neurotoxicity. Disturbingly, there is no vaccine or specific drug to prevent or treat the diseases caused by ZIKV infection. Thus, it is extremely urgent to characterize the pathogenesis of ZIKV. It has been documented that ZIKV can evade antiviral responses of host cells. Here, we demonstrate that ZIKV strain SZ-WIV01 down-regulates the production of type I IFN and IFN-stimulated genes along with the expression of mitochondrial antiviral signaling protein (MAVS) and mediator of IFN regulatory factor 3 activation (MITA). In the mechanism, ZIKV nonstructural (NS) 3 and NS2B3 negatively regulate IFN-related retinoic acid-inducible gene I-like receptor signaling pathway by targeting MAVS and MITA, respectively. Overexpression of ZIKV NS3 and NS2B3 dramatically inhibits expression of IFN-β. ZIKV NS3 interacts with MAVS, and NS2B3 interacts with MITA, which catalyzes K48-linked polyubiquitination of MAVS and MITA for degradation. Further investigations suggest that ZIKV NS2B3 impairs polyinosinic:polycytidylic acid-triggered K63-linked polyubiquitination of MITA, thereby subverting the activation of downstream sensors. Our study reveals an undiscovered mechanism for ZIKV to escape the innate immune response, providing new insights into clinical study of vaccines or effective drugs.-Li, W., Li, N., Dai, S., Hou, G., Guo, K., Chen, X., Yi, C., Liu, W., Deng, F., Wu, Y., Cao, X. Zika virus circumvents host innate immunity by targeting the adaptor proteins MAVS and MITA.
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http://dx.doi.org/10.1096/fj.201900260RDOI Listing
September 2019

Randomized controlled trial on adjunctive cognitive remediation therapy for chronically hospitalized patients with schizophrenia.

Shanghai Arch Psychiatry 2012 Jun;24(3):149-54

Third People's Hospital of Lanzhou Municipality, Lanzhou, Gansu Province, China.

Background: Cognitive remediation therapy (CRT) is one of the promising new non-drug approaches to reducing cognitive deficits of patients with schizophrenia that has not yet been fully evaluated in China.

Aim: Assess the efficacy of CRT in improving the cognitive functioning, social functioning and insight of patients with chronic schizophrenia.

Methods: 126 clinically stable inpatients with chronic schizophrenia were randomly allocated to an intervention group (with CRT) and a treatment as usual group (TAU) (which used standard occupational and recreational therapy methods). The treatment frequency and duration were the same for the two groups: five times per week for three months. The Wisconsin Card Sorting Test (WCST) was used to evaluate before versus after changes in cognitive function, the Scale of Social Skills of chronic schizophrenia Inpatients (SSSI) was used to assess social functioning, and the Insight and Treatment Attitude Questionnaire (ITAQ) was use to assess insight.

Results: Four patients dropped out during the study leaving 60 in the CRT group and 62 in the TAU group in the final analysis. Both groups showed significant improvement in WCST measures over the three-month trial but the improvement in the CRT group was significantly greater than that for the TAU group on all of the WCST measures assessed. The total SSSI score improved significantly in both groups over the three months, but the improvement in the two groups was not significantly different. The total ITAQ score also showed significant improvement in both groups over the three months and the degree of improvement was significantly greater in the CRT group than in the TAU group.

Conclusion: As an adjunctive treatment to antipsychotic medication, a three month course of CRT is more effective at improving the cognitive functioning and insight of hospitalized patients with chronic schizophrenia than routine occupational and recreational therapy.
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http://dx.doi.org/10.3969/j.issn.1002-0829.2012.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198846PMC
June 2012
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