1.Linagliptin synergizes with cPLA2 inhibition to enhance temozolomide efficacy by interrupting DPP4-mediated EGFR stabilization in glioma.
Dongyuan SU ; Biao HONG ; Shixue YANG ; Jixing ZHAO ; Xiaoteng CUI ; Qi ZHAN ; Kaikai YI ; Yanping HUANG ; Jiasheng JU ; Eryan YANG ; Qixue WANG ; Junhu ZHOU ; Yunfei WANG ; Xing LIU ; Chunsheng KANG
Acta Pharmaceutica Sinica B 2025;15(7):3632-3645
The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.
2.Optimization of the control strategy and research priorities to combat the resurgence of visceral leishmaniasis in China
Xiaonong ZHOU ; Shizhu LI ; Junhu CHEN ; Yi ZHANG
Chinese Journal of Schistosomiasis Control 2024;36(4):329-333
Leishmaniasis is a zoonotic parasitic disease caused by Leishmania infection and transmitted by sandflies. There are three main forms of leishmaniasis, including cutaneous leishmaniasis, visceral leishmaniasis and mucocutaneous leishmaniasis. China is mainly endemic for visceral leishmaniasis, which is a class C notifiable infectious disease in the country. Following concerted efforts, the transmission of visceral leishmaniasis had been controlled in most endemic foci of China by the end of 1958, with a few cases reported in western China. Due to global climate changes and population mobility, resurgence of visceral leishmaniasis has recently occurred in historical endemic areas of central and western China, which is characterized by gradual expansion of endemic areas and remarkable rebounding epidemics. Hereby, we summarize the national and global epidemiology and control strategy of visceral leishmaniasis, propose 8 key research areas and 12 key research topics for visceral leishmaniasis control, and recommend the establishment of the joint prevention and control mechanism of “human-animals-vectors” and the working mechanism of animal prevention for human diseases based on the One Health approach, so as to combat the resurgence of visceral leishmaniasis in China.
3.Expert consensus on the construction of surveillance pathways and systems for vector-borne tropical diseases
CHEN Junhu ; WEN Liyong ; LI Shizhu ; WANG Shanqing ; LIU Qiyong ; ZHAO Tongyan ; XIE Qing ; ZHOU Xiaonong ; Consensus Expert Group
China Tropical Medicine 2024;24(3):233-
With the growth of the global economy , changes in climate and ecological environments, and increased mobility of humans and animals, the transmission risk of vector-borne tropical diseases continues to rise. To address this challenge, strengthening surveillance of vector-borne tropical diseases is urgent. This consensus brought together 29 renowned experts in related professional fields from 26 institutions in China, who, through analyzing the epidemic trend and hazard situation of vector-borne tropical diseases and summarizing the working experiences of experts, have firstly reached following consensus: the burden of vector-borne tropical diseases is heavy with great threats to human health; China has achieved remarkable results in prevention and control of vector-borne tropical diseases , but still needs to strengthen the surveillance and response actively. Secondly, a unanimous consensus has been reached on the aspects of surveillance definition, objectives, contents, and methods of vector-borne tropical diseases. Thirdly, detail requirements have been agreed including: strengthening the concept of early surveillance and forecast, standarding the function, evaluation steps, and construction requirements of surveillance system for vector-borne tropical diseases. Fourthly, key tasks were put forward that need to be investigated and strengthened in the future. This expert consensus provides a standardized reference for the construction of the surveillance pathway and surveillance system for vector-borne tropical diseases in China.
4.Bibliometric analysis of researches on the Plasmodium falciparum repetitive interspersed families of polypeptides protein from 1993 to 2022
Jingxian YIN ; Zhishan SUN ; Hanqing ZHAO ; Xiaonong ZHOU ; Kokouvi KASSEGNE ; Junhu CHEN
Chinese Journal of Schistosomiasis Control 2024;36(2):184-190
Objective To perform a bibliometric analysis of researches on the Plasmodium falciparum repetitive interspersed families of polypeptides (RIFIN) protein from 1993 to 2022 and identify the hot topics in the RIFIN protein research, so as to provide insights into future researches on RIFIN protein. Methods RIFIN protein-associated publications were retrieved in the Web of Science Core Collection from 1993 to 2022 and all bibliometric analyses were performed using the software CiteSpace 6.2.4.0. The annual number of RIFIN protein-associated publications was analyzed from 1993 to 2022, and country, author and institution collaboration networks were created. Keywords were extracted from RIFIN protein-associated publications for plotting keyword co-occurrence, clustering, burst and timeline maps to identify the hot topics in the RIFIN protein research. Results A total of 745 English RIFIN protein-associated publications were included in the final bibliometric analysis, and there were 18 to 36 publications each year from 1993 to 2022. The top three countries with the highest activity in the RIFIN protein research included the United States, the United Kingdom and France, universities and research institutes were highly active in the RIFIN protein research; however, no authors were identified with a high activity in the RIFIN protein research. There were three keyword clusters in the RIFIN protein-associated publications, including repetitive DNA sequence, molecular epidemiology and antigenic variation. Keyword co-occurrence, burst and timeline analyses showed that previous RIFIN protein-associated publications mainly focused on gene properties and functions, involving keywords of repetitive DNA sequence and evolution, and recent hot topics for the RIFIN protein research shifted to genetic diversity and immune response, involving keywords of genetic diversity, antigenic variation and binding. Conclusions The annual number of RIFIN protein-associated publications was relatively stable from 1993 to 2022. This bibliometric analysis may provide insights into future researches on the RIFIN protein.
5.Enzyme production mechanism of anaerobic fungus Orpinomyces sp. YF3 in yak rumen induced by different carbon source.
Xue'er DU ; Linlin ZHOU ; Fan ZHANG ; Yong LI ; Congcong ZHAO ; Lamei WANG ; Junhu YAO ; Yangchun CAO
Chinese Journal of Biotechnology 2023;39(12):4927-4938
In order to investigate the enzyme production mechanism of yak rumen-derived anaerobic fungus Orpinomyces sp. YF3 under the induction of different carbon sources, anaerobic culture tubes were used for in vitro fermentation. 8 g/L of glucose (Glu), filter paper (Flp) and avicel (Avi) were respectively added to 10 mL of basic culture medium as the sole carbon source. The activity of fiber-degrading enzyme and the concentration of volatile fatty acid in the fermentation liquid were detected, and the enzyme producing mechanism of Orpinomyces sp. YF3 was explored by transcriptomics. It was found that, in glucose-induced fermentation solution, the activities of carboxymethyl cellulase, microcrystalline cellulase, filter paper enzyme, xylanase and the proportion of acetate were significantly increased (P < 0.05), the proportion of propionate, butyrate, isobutyrate were significantly decreased (P < 0.05). The results of transcriptome analysis showed that there were 5 949 differentially expressed genes (DEGs) between the Glu group and the Flp group, 10 970 DEGs between the Glu group and the Avi group, and 6 057 DEGs between the Flp group and the Avi group. It was found that the DEGs associated with fiber degrading enzymes were significantly up-regulated in the Glu group. Gene ontology (GO) function enrichment analysis identified that DEGs were mainly associated with the xylan catabolic process, hemicellulose metabolic process, β-glucan metabolic process, cellulase activity, endo-1,4-β-xylanase activity, cell wall polysaccharide metabolic process, carbohydrate catabolic process, glucan catabolic process and carbohydrate metabolic process. Moreover, the differentially expressed pathways associated with fiber degrading enzymes enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were mainly starch and sucrose metabolic pathways and other glycan degradation pathways. In conclusion, Orpinomyces sp. YF3 with glucose as carbon source substrate significantly increased the activity of cellulose degrading enzyme and the proportion of acetate, decreased the proportion of propionate, butyrate and isobutyrate. Furthermore, the degradation ability and energy utilization efficiency of fungus in the presence of glucose were improved by means of regulating the expression of cellulose degrading enzyme gene and participating in starch and sucrose metabolism pathway, and other glycan degradation pathways, which provides a theoretical basis for the application of Orpinomyces sp. YF3 in practical production and facilitates the application of Orpinomyces sp. YF3 in the future.
Animals
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Cattle
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Neocallimastigales/metabolism*
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Anaerobiosis
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Rumen/microbiology*
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Propionates/metabolism*
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Isobutyrates/metabolism*
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Cellulose/metabolism*
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Fungi
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Starch/metabolism*
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Glucose/metabolism*
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Acetates
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Sucrose/metabolism*
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Cellulases
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Cellulase
6.Evaluation value of intravascular optical coherence tomography for carotid atherosclerotic plaques
Jun ZHOU ; Yongnan HAO ; Shuhu ZHOU ; Yan DONG ; Lin WANG ; Zhongqing ZHAO ; Junhu ZHANG
International Journal of Cerebrovascular Diseases 2022;30(6):420-425
Objective:To investigate the evaluation value of optical coherence tomography (OCT) for carotid atherosclerotic plaques.Methods:Patients with carotid atherosclerotic stenosis underwent digital subtraction angiography (DSA) and OCT in the Affiliated Hospital of Jining Medical College from January 2020 to January 2022 were retrospectively enrolled. The demographics, baseline clinical data, DSA and OCT imaging data of the symptomatic group and the asymptomatic group were compared. Multivariate logistic regression analysis was used to determine the independent risk factors for symptomatic carotid atherosclerotic stenosis. Results:A total of 39 patients were enrollded, including 21 in the symptomatic group and 18 in the asymptomatic group. The detection rate of fibrous plaque in the symptomatic group was significantly lower than that in the asymptomatic group (38.1% vs. 77.78%; P=0.023), while the detection rate of plaque rupture (38.1% vs. 5.56%; P=0.023) and macrophage infiltration (42.86% vs. 11.11%; P=0.037) was significantly higher than that in the asymptomatic group. Multivariate logistic regression analysis showed that plaque rupture (odds ratio 6.982, 95% confidence interval 1.068-45.660; P=0.043) and macrophage infiltration (odds ratio 6.480, 95% confidence interval 1.009-41.625; P=0.049) were significantly independently associated with the symptomatic carotid atherosclerotic stenosis. Conclusions:OCT is of value in evaluating the plaque characteristics of carotid atherosclerotic stenosis. Plaque rupture and macrophage infiltration are the independent risk factors for symptomatic carotid atherosclerotic stenosis.
7.Effect of kinase PLK4 on the proliferation of glioma cells in vitro
Zuoxin ZHANG ; Junhu ZHOU ; Lei HAN
Chinese Journal of Clinical Oncology 2017;44(14):685-688
Objective:To analyze the correlation of protein kinase PLK4 with the prognosis of patients with malignant glioma and the proliferation of human glioblastoma cells. Methods:The relationship of PLK4 expression to the pathological grade and prognosis was evaluated using CGGA datasets. Designated siRNAs targeting PLK4 were constructed, and the silencing effect was identified by RT-qP-CR and Western blot analyses. The effect of PLK4 on the proliferation of tumor cells was evaluated by MTT and colony formation as-says. Results:The expression of PLK4 increased with pathological grade and was significantly related to the overall survival in patients with glioma and the prognosis of patients with high-grade glioma. MTT and colony formation assay results indicated that the prolifera-tion activity was significantly reduced after depleting PLK4. Conclusion:The expression of PLK4 is related to the prognosis of patients with glioma and can affect the proliferation activity of tumor cells. Therefore, PLK4 could be a potential therapeutic target in glioma treatment.
8.Clinical observation on therapeutic effect of bloodletting therapy for treatment of patients with piriformis injury syndrome
Wei ZHOU ; Junhu MA ; Hua LEI ; Fuquan JING ; Yu ZHOU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2017;24(3):313-315
Objective To observe the curative effect of pricking bloodletting combined with acupuncture on patients with piriformis injury syndrome.Methods A prospective randomized controlled clinical trial was conducted, 84 patients with piriformis injury syndrome admitted to the Department of Acupuncture and Massage in the First Affiliated Hospital of Xinjiang Medical University from May 2011 to May 2014 were enrolled, and they were divided into observation group and control group by random number table, each group being 42 cases. The patients in the observation group were treated with bloodletting once a week (after bloodletting no other treatment was given), and then once a day of acupuncture was performed for 4 days in a week, completing one therapeutic course; while in the control group, the patient was treated with routine acupuncture once a day for 5 days in a week, finishing one therapeutic course. The interval between two therapeutic courses was 2 days, two courses were carried out, and afterwards the clinical therapeutic effects were evaluated in the two groups. The changes of visual analogue scale (VAS) of two groups before and after treatment and the therapeutic effects were observed.Results The VAS score of the two groups after treatment was lower than that before treatment, and the degree of decrease of VAS score in the observation group was significantly lower than that of thecontrol group (1.50±1.35 vs. 2.69±1.68,P < 0.01); the total effective rate in the observation group was obviously higher than that in the control group [100.00% (42/42) vs. 69.05% (29/42),P < 0.01].Conclusion Pricking bloodletting combined with acupuncture therapy for treatment of piriformis injury syndrome can shorten the course of treatment.
9.Meta analysis for clinical efficacy of head needle treatment in children with cerebral palsy
Xianglai NIU ; Junhu MA ; Wei ZHOU ; Lina FANG ; Lijuan TIAN ; Yu ZHOU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2015;(4):347-350
Objective To evaluate the clinical curative effect of acupuncture and moxibustion treatment for children with cerebral palsy by Meta analysis.Methods The Chinese biomedical literature database (CBM), CNKI and Wanfang data, Weipu data, PubMed, EMbase and Cochrane central registration of controlled clinical trials were searched. All the randomized controlled trials (RCTs) of acupuncture and other conventional treatment for infantile cerebral palsy before December 2013 were retrieved. Meta analysis was conducted with Review Manage 5.2 software.Results Finally, 11 reports of RCT were enrolled in the study, including 979 patients. Meta analysis showed that the total effective rate of acupuncture treatment for infantile cerebral palsy was significantly higher than that in the control group [odds ratio (OR) = 4.08, 95% confidence interval (95%CI) = 2.86 - 5.83,P < 0.000 01]. Funnel chart analysis showed no publication bias in the chosen literature.Conclusion The therapeutic effect of acupuncture combined with rehabilitation therapy is superior to that of other conventional treatment for children with cerebral palsy.
10.Blood-letting therapy combined with acupuncture for 50 cases of ankle joint sprain.
Wei ZHOU ; Xianglai NIU ; Junhu MA
Chinese Acupuncture & Moxibustion 2015;35(1):43-43
Acupuncture Therapy
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Adolescent
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Adult
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Aged
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Ankle Injuries
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therapy
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Bloodletting
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Combined Modality Therapy
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Female
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Humans
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Male
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Middle Aged
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Young Adult

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