4.Research progress of small molecule modulators targeting Toll-like receptor 2
Jia-hua KE ; Dan-lei CHEN ; Kui CHENG
Acta Pharmaceutica Sinica 2023;57(8):2239-2249
Toll like receptors (TLRs) are the earliest discovered natural immune pattern recognition receptors (PRRs). The abnormality of TLR signal transduction pathway is the key factor leading to chronic inflammatory, cancer, nervous system disease and cardiovascular diseases. The development of TLR agonists and inhibitors has attracted much attention. Currently known TLR2 agonists, such as lipopeptides or their derivatives, have certain limitations in drug development due to their difficult synthesis, easy hydrolysis, and triggering inflammatory cytokine storms, while inhibitors have been rarely reported. New small molecule TLR2 agonists or inhibitors with higher stability are more likely to be developed as tumor immunotherapy or anti-inflammatory drugs.
5.Localized amyloidosis concurrently involving the nasopharynx, larynx and nasal cavities: a case report.
Ke-Jia CHENG ; Shen-Qing WANG ; Shan LIN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2009;44(10):875-876
Amyloidosis
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pathology
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Humans
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Laryngeal Diseases
;
etiology
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Larynx
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pathology
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Male
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Middle Aged
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Nasopharynx
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pathology
6.HPV DNA vaccines expressing recombinant CRT/HPV6bE7 fusion protein inhibit tumor growth and angiogenic activity.
Yan XU ; Hao CHENG ; Ke-Jia ZHAO ; Ke-Jian ZHU ; Xing ZHANG
Chinese Journal of Virology 2007;23(6):466-470
This paper was to study the angiogenic inhibitory effect and the potential antitumor effect of the constructed recombinant DNA vaccine CRT/HPV6bE7 in vivo. The C57BL/6 mice were vaccinated respectively with recombinant CRT/HPV6bE7 DNA plamids. The inhibitory effects on angiogenesis of generated vaccines in vivo were evaluated by a bFGF-induced angiogenesis assay using the Matrigel kit. To investigate the potential antitumor effect, the mean tumor weights, sizes and tumor appearing times were measured in C57BL/6 mice treated with HPV6bE7-expressing B16 cells. The results indicated that the recombinants CRT180/HPV6bE7 and CRT180 showed strong anti-angiogenic effects in bFGF-induced angiogenesis in vivo. Moreover, CRT180/HPV6bE7 and CRT180 DNA vaccines could significantly inhibit the tumor growth in tumor challenge experiment, and CRT180/HPV6bE7 was superior to other vaccines in delaying tumor formation time, limiting tumor size and weight in tumor protection experiment. In conclusion, recombinant CRT180/HPV6bE7 DNA could elicit a most efficient anti-angiogenic effect and inhibit tumor growth in mice inoculated with DNA vaccines. The antiangiogenic activity of CRT were suggested residing in a domain between CRT 120-180 aa.
Animals
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Calreticulin
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genetics
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Female
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Human papillomavirus 6
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immunology
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Mice
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Mice, Inbred C57BL
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Neovascularization, Pathologic
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prevention & control
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Oncogene Proteins, Viral
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genetics
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Papillomavirus Infections
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therapy
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Papillomavirus Vaccines
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immunology
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Recombinant Fusion Proteins
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genetics
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Vaccines, DNA
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immunology
7.Effects of acupuncture on distribution taxis of paclitaxel in mice with lung cancer.
Zhi-Xing ZHANG ; Ze-Dong CHENG ; Chun-Ri LI ; Ai-Jun KE ; Jia-Li CHEN ; Yi-Guo CHEN
Chinese Acupuncture & Moxibustion 2014;34(12):1208-1213
OBJECTIVETo observe the effects of acupuncture at "Feishu" (BL 13) and "Lingtai" (GV 10) on distribution taxis of paclitaxel in mice with lung cancer to discuss targeted relationship between acupoints and corresponding viscera.
METHODSAccording to randomized digital table, 315 SPF-grade BALB/C female mice were divided into 7 groups: blank group (group A), model group (group B), medication group (group C), acupuncture at non-acupoint group (group D), acupuncture at Feishu group (group E), acupuncture at Lingtai group (group F) and acupuncture at Feishu and Lingtai group (group G), 45 mice in each one. Except the blank group, the remaining groups were treated with N-nitroso-tris-chloroethyl urea (NTCU) to establish the model of squamous-cell carcinoma. After model establishment, group A, group B and group C were not treated with acupuncture; group A and group B were treated with intraperitoneal injection of 0.9% sodium chlorvde solution by 6 mL/kg while group C was treated with intraperitoneal injection of paclitaxel by 6 mL/kg. The group D, group E, group F and group G were treated with acupuncture at non-acupoint, "Feishu" (BL 13), "Lingtai" (GV 10) and "Feishu" (BL 13) plus "Lingtai" (GV 10), respectively, then were intraperitoneally injected with paclitaxel by 6 mL/kg. The treatment was all given once a day for continuous 10 days. 15 min, 30 min, 1 h, 2 h, 8 h, 12 h and 24 h after the treatments, 6 mice in each group were randomly selected and sacrificed to collect samples of lung, liver, spleen, kidney and heart, etc. High performance liquid chromatography was applied to measure the concentration of paclitaxel in each organ (lung, liver, spleen, kidney and heart) at different time points.
RESULTS(1) The content of paclitaxel in lung, kidney and heart reached the peak at 2 h, then decreased significantly in group C, group D, group E, group F and group G; the content of paclitaxel in spleen showed downtrend at each time point. The content of paclitaxel in liver reached the peak at 2 h in group C and group D; the content of paclitaxel reached the peak at 8 h in group E, group F and group G. (2) The content of paclitaxel in lung in group E and group G was higher than that in group C and group D at each time point (all P < 0.01); the content of paclitaxel in lung in group F was higher than that in group C (P < 0.01) and group D (P < 0.01) only at time point of 2 h. The content of paclitaxel in lung in group G was higher than that in group F at each time point (all P < 0.05). There was no statistical difference between group G and group E (all P > 0.05).
CONCLUSIONAcupuncture at "Feishu" (BL 13) and "Lingtai" (GV 10) could influ- ence the metabolism of paclitaxel in lung-cancer mice, leading to distribution change in each organ. As a result, it could cause targeting effects, which is more significant at "Feishu" (BL 13) and "Lingtai" (GV 10).
Acupuncture Points ; Acupuncture Therapy ; Animals ; Antineoplastic Agents, Phytogenic ; pharmacokinetics ; Drugs, Chinese Herbal ; pharmacokinetics ; Female ; Humans ; Lung Neoplasms ; drug therapy ; therapy ; Mice ; Mice, Inbred BALB C ; Paclitaxel ; pharmacokinetics ; Taxus ; chemistry
8.Serum ECP levels in patients with allergic rhinitis and chronic rhinosinusitis..
Ke-Jia CHENG ; Shen-Qing WANG ; Ying-Ying XU ; Hong-Yan LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2009;44(12):1001-1005
OBJECTIVETo investigate the serum eosinophil cationic protein (ECP) levels in patients with allergic rhinitis (AR) or chronic rhinosinusitis with polyps(CRSWP), and its relations with allergic symptoms in patients with AR.
METHODSThe ECP in serum and Phadiatop tests were detected by UniCAP100 system. Blood sample was taken from 87 patients with inhaled AR, 49 patients with CRSWP and 20 healthy individuals. The serum ECP levels were detected by enzyme-linked immunosorbent assay. The allergic symptoms in patients with inhaled AR were graded.
RESULTSPhadiatop level was 5185.0 [983.0, 14469.0] Fu in inhaled AR, 317.5 [125.0, 526.8] Fu in CRSWP with Phadiatop positive, 30.0 [28.0, 43.0] Fu in CRSWP with Phadiatop negative and 43.5 [29.0, 105.0] Fu in healthy individuals. The level of ECP in patients with inhaled AR was 24.8 [14.6, 49.1] microg/L, higher than that in CRSWP with Phadiatop positive 7.7 [3.3, 25.6] microg/L, CRSWP with Phadiatop negative 12.5 [6.7, 16.7] microg/L and control 8.8 [5.4, 20.2] microg/L. The difference was significant. There were correlations among the allergic symptoms, serum ECP and Phadiatop levels.
CONCLUSIONSAmong patients with inhaled AR, there was an up-regulated concentration of serum ECP, which had relations to allergic symptoms. The detection of serum ECP could be used as a convenient screening test for inhaled AR. Its concentration had correlation with the severity and prognosis of the disease. To the contrary, the serum ECP did not significantly increased in patients with CRSWP.
Chronic Disease ; Eosinophil Cationic Protein ; blood ; Humans ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; blood ; Sinusitis
9.Expression and variation of MIP-1β, MIP-2, and IL-12p70 in mouse models with bloodstream infection caused by different bacteria
Ming YANG ; Ya-Ting MA ; Shang HE ; Xin-Xin DUAN ; Jia-Nan WANG ; Ying JING ; Ke-Xin ZHANG ; Cheng-Bin WANG
Chinese Journal of Infection Control 2017;16(11):993-998
Objective To investigate the expression and variation of MIP 1β,MIP-2,and IL-12p70 in mice with bloodstream infection caused by 4 kinds of bacteria.Methods CD-1 (ICR) mouse models of bloodstream infection with Staphylococcus aureus (S.aureus),Enterococcus f aecalis (E.f aecalis),Escherichia coli (E.coli),and K lebsiella pneumoniae (K.pneumoniae) were established.After mice in each trial group and PBS control group were infected by bacteria for 0.5h,1h,3h,6h,12h,24h,and 48h,concentrations of MIP-1β,MIP-2,and IL-12p70 were detected by Luminex liquid suspension chip system.Results Concentrations of MIP-1β increased significantly 1h after bacteria was in blood,S.aureus,E.faecalis,E.coli,K.pneumoniae,and control groups were (134.5 ± 18.3),(61.5 ± 15.4),(3 354.0 ±809.0),(6 888.4 ± 1 100.2),and (28.9 ± 4.6) pg/mL respectively;the peak values of IL-12p70 were (389.3 ± 118.1),(127.6 ± 10.0),(42.2 ± 3.5),(62.8 ± 8.4),and (4.8 ± 0.3) pg/mL respectively.Concentrations of MIP-1β and MIP-2 in E.coli and K.pneumoniae groups were significantly higher than other trial groups and control group (all P<0.01),while concentrations of IL-12p70 in S.aureus and E.faecalis groups were both significantly higher than E.coli,K.pneumoniae,and control groups (all P<0.01).Conclusion Concentrations of MIP-1β and MIP-2 in E.coli and K.pneumoniae groups were both significantly higher than those in S.aureus and E.faecalis groups,while concentrations of IL-12p70 in S.aureus and E.faecalis groups were both significantly higher than those in E.coli and K.pneumoniae groups.The combination detection of multiple cytokines or chemokines are valuable in predicting gram-positive or gram-negative bacterial infection,and can provide basis for treatment of early infection.
10.MiR-214 Regulates the Human Hair Follicle Stem Cell Proliferation and Differentiation by Targeting EZH2 and Wnt/β-Catenin Signaling Way In Vitro.
Ke Tao DU ; Jia Qin DENG ; Xu Guang HE ; Zhao ping LIU ; Cheng PENG ; Ming Sheng ZHANG
Tissue Engineering and Regenerative Medicine 2018;15(3):341-350
miR-214 plays a major role in the self-renewal of skin tissue. However, whether miR-214 regulates the proliferation and differentiation of human hair follicle stem cells (HFSCs) is unknown. Primary HFSCs were isolated from human scalp skin tissue, cultured, and identified using flow cytometry. An miR-214 mimic and inhibitor were constructed for transfection into HFSCs. The MTS and colony formation assays examined cell proliferation. Immunofluorescence detected the localization and expression levels of TCF4, β-catenin, and differentiation markers. Luciferase reporter and TOP/FOP Flash assays investigated whether miR-214 targeted EZH2 and regulated the Wnt/β-catenin signaling pathway. Western blot determined the expression levels of enhancer of zeste homolog 2 (EZH2), Wnt/β-catenin signaling-related proteins, and HFSC differentiation markers in cells subjected to miR-214 transfection. miR-214 expression was remarkably decreased during the proliferation and differentiation of HFSCs into transit-amplifying (TA) cells. Downregulation of miR-214 promotes the proliferation and differentiation of HFSCs. Overexpression of miR-214 led to decreased expression of EZH2, β-catenin, and TCF-4, whereas downregulation of miR-214 resulted in increased expression of EZH2, β-catenin, and TCF-4 as well as TA differentiation markers. Immunofluorescence assay revealed that inhibiting miR-214 triggered the entry of β-catenin and TCF-4 into the nucleus. The luciferase reporter and TOP/FOP Flash assays demonstrated that miR-214 directly targets EZH2 and affects Wnt/β-catenin signaling. The miR-214/EZH2/β-catenin axis could be considered a candidate target in tissue engineering and regenerative medicine for HFSCs.
Antigens, Differentiation
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Blotting, Western
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Cell Proliferation
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Down-Regulation
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Flow Cytometry
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Fluorescent Antibody Technique
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Hair Follicle*
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Hair*
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Humans*
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In Vitro Techniques*
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Luciferases
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Regenerative Medicine
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Scalp
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Skin
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Stem Cells*
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Tissue Engineering
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Transfection