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1.
Acta Pharmacol Sin ; 43(3): 659-671, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34103688

ABSTRACT

Tubulointerstitial inflammation plays an important role in the progression of diabetic nephropathy (DN), and tubular epithelial cells (TECs) are crucial promoters of the inflammatory cascade. Exchange protein activated by cAMP (Epac) has been shown to suppress the angiotensin II (Ang-II)-induced release of inflammatory cytokines in tubular cells. However, the role of Epac in TEC-mediated tubulointerstitial inflammation in DN remains unknown. We found that administering the Epac agonist 8-pCPT-2'-O-Me-cAMP (8-O-cAMP) to db/db mice inhibited tubulointerstitial inflammation characterized by macrophage infiltration and increased inflammatory cytokine release and consequently alleviated tubulointerstitial fibrosis in the kidney. Furthermore, 8-O-cAMP administration restored CCAAT/enhancer binding protein ß (C/EBP-ß) expression and further upregulated the expression of Suppressor of cytokine signaling 3 (SOCS3), while inhibiting p-STAT3, MCP-1, IL-6, and TNF-α expression in the kidney cortex in db/db mice. And in vitro study showed that macrophage migration and MCP-1 expression induced by high glucose (HG, 30 mM) were notably reduced by 8-O-cAMP in human renal proximal tubule epithelial (HK-2) cells. In addition, 8-O-cAMP treatment restored C/EBP-ß expression in HK-2 cells and promoted C/EBP-ß translocation to the nucleus, where it transcriptionally upregulated SOCS3 expression, subsequently inhibiting STAT3 phosphorylation. Under HG conditions, siRNA-mediated knockdown of C/EBP-ß or SOCS3 in HK-2 cells partially blocked the inhibitory effect of Epac activation on the release of MCP-1. In contrast, SOCS3 overexpression inhibited HG-induced activation of STAT3 and MCP-1 expression in HK-2 cells. These findings indicate that Epac activation via 8-O-cAMP ameliorates tubulointerstitial inflammation in DN through the C/EBP-ß/SOCS3/STAT3 pathway.


Subject(s)
Diabetic Nephropathies/pathology , Guanine Nucleotide Exchange Factors/agonists , Inflammation/pathology , Kidney Tubules/drug effects , Animals , CCAAT-Enhancer-Binding Protein-beta/drug effects , Cyclic AMP/analogs & derivatives , Cyclic AMP/pharmacology , Cytokines/drug effects , Humans , Inflammation Mediators/metabolism , Macrophages/drug effects , Mice , Mice, Inbred C57BL , Random Allocation , STAT3 Transcription Factor/drug effects , Signal Transduction/drug effects , Suppressor of Cytokine Signaling 3 Protein/drug effects , Up-Regulation
2.
Zool Res ; 40(6): 552-557, 2019 Nov 18.
Article in English | MEDLINE | ID: mdl-31592584

ABSTRACT

A blind fish of Sinocyclocheilus (Cypriniformes: Cyprinidae) was caught in open water in the Three Gorges (Sanxia) reservoir, at a depth of 20 m in the mainstream of Yangtze River in Zigui County, Hubei Province, China. This fish can be easily distinguished from all other congeners by external morphological characteristics, and is estimated to have diverged from its sister group about 0.55 million years ago (Ma). The geologically well separated locality of this species has expanded the distribution of Sinocyclocheilus cavefish from around N25°(latitude) to above N30°. Herein, we describe this new species as Sinocyclocheilus sanxiaensis sp. nov., and discuss the possible reasons why the species appears, surprisingly, in the Three Gorges reservoir.


Subject(s)
Caves , Cyprinidae/anatomy & histology , Cyprinidae/classification , Rivers , Animals , China , Cyprinidae/genetics , Phylogeny , Species Specificity
3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-816383

ABSTRACT

OBJECTIVE: To offer some important insights into clinical decision-making by evaluating endorectal ultrasound and rectal MRI when they were used to predict pathological complete response for rectal cancer patients who were performed neoadjuvant therapy. METHODS: The study was a prospective cohort study which was conducted at a single tertiary care center. Patients diagnosed with mid-low rectal cancer between May 2014 and June 2018 in Peking Union Medical College Hospital were collected in the study. Both of their endorectal ultrasound and rectal MRI were performed to evaluate the tumor stage before their preoperative chemoradiation and were reevaluated at the 6 to 7 th weeks after their preoperative radiation treatment. The pathological preoperative tumor staging achieved by endorectal ultrasound and rectal MRI was compared with postoperative staging by pathologic examination. Sensitivity,specificity,accuracy and Youden index of each evaluation method and their combination were calculated. The ROC curve was administered likewise. RESULTS: A total of 247 patients were enrolled in the study. The sensitivity,specificity,accuracy,positive predictive value,negative predictive value and Youden index for ypT0 N0 separate evaluation of for whom was qualified as compete endorectal ultrasound(163 patients) and of rectal MRI(212 patients) was15.9% and 23.1%,94.0% and 94.9%,77.8% and 83.4%,0.1 and 0.2. Combined two methods,the data were recorded as 13.6%,98.1%,83.6% and 0.1.Area under curve ROC for ultrasound and MRI when using specifically for ypT0 N0 measurement was 0.656 and 0.742.The two modalities showed 0.517 and 0.667 in terms of AUC when comparing with each other. CONCLUSION: The sensitivity of MRI and ERUS as terms of diagnosing complete response is rather unsatisfactory,although they all bear a relatively good specificity. For the patients not diagnosed with clinical response by one of the two methods,radical operations were strongly recommended. For the patients confirmed as complete response by both modalities,there still exists possibilities that residual tumor persists,“watch and wait”approach can be taken cautiously and the patient must be followed up intensely.

4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-657356

ABSTRACT

Objective To explore the research status quo, hotspots and developing trends of Kazakh medicine. Methods Relevant literature of Kazakh medicine published from January of 1990 to December of 2015 was retrieved from CNKI and Wanfang database. Bibliographic information data were set as the research objects for data cleaning and data conversion. Metrological analysis was conducted from publication number, publication units, key words, and authors. Ucinet, CiteSpace, SATI and R language were used as analysis tools to construct social network and shared network. Results After screening, 142 articles were included. Institute of cooperative social network standardization center point penetration potential was 8.475%; top 3 high-yield authors were Mulati Kiaibek (10 articles), Alhin?Dakai (8 articles) and Maldives Jiang (7 articles); author co-citation map had a total of 189 nodes, 141 lines, and density of 0.007 9; key words were six element theory, traditional therapy, Soerbuen and Qieketarbe. Conclusion Kazakh medicine research is in the initial stage. The distribution of Kazakh medicine research team is relatively concentrated, while the hotspots of research were scattered. Featured medical resources of Kazakh medicine is with large space for mining.

5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-659340

ABSTRACT

Objective To explore the research status quo, hotspots and developing trends of Kazakh medicine. Methods Relevant literature of Kazakh medicine published from January of 1990 to December of 2015 was retrieved from CNKI and Wanfang database. Bibliographic information data were set as the research objects for data cleaning and data conversion. Metrological analysis was conducted from publication number, publication units, key words, and authors. Ucinet, CiteSpace, SATI and R language were used as analysis tools to construct social network and shared network. Results After screening, 142 articles were included. Institute of cooperative social network standardization center point penetration potential was 8.475%; top 3 high-yield authors were Mulati Kiaibek (10 articles), Alhin?Dakai (8 articles) and Maldives Jiang (7 articles); author co-citation map had a total of 189 nodes, 141 lines, and density of 0.007 9; key words were six element theory, traditional therapy, Soerbuen and Qieketarbe. Conclusion Kazakh medicine research is in the initial stage. The distribution of Kazakh medicine research team is relatively concentrated, while the hotspots of research were scattered. Featured medical resources of Kazakh medicine is with large space for mining.

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