Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2017-12-07 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To investigate the effect of chloroquine on airway hyperresponsiveness in asthmatic mice and explore the possible mechanism. Methods Balb/c mouse models of asthma established using OVA received intraperitoneal injections of chloroquine, dexamethasone, or both prior to OVA challenge. Within 24 h after the final challenge, airway hyper-responsiveness (AHR) of the mice was assessed, and the total cell count and the counts of different cell populations in the bronchoalveolar lavage fluid (BALF) were determined under light microscopy The severity of lung inflammation was evaluated using HE staining, and the concentrations of IL-6 and PGFzx in the BALF were detected by enzyme-linked immunosorbent assay (ELISA). Results Chloroquine pretreatment significantly decreased AHR (P<0.001) in the asthmatic mice and reduced the total cell count (P<0.01), eosinophils (P<0.001), neutrophils (P<0.01), and PGF} levels in the BALE Chloroquine combined with low-dose dexamethasone significantly lessened inflammations around the bronchioles (P<0.05) and blood vessels (P<0.01) in the lung tissue, and obviously lowered IL-6 (P<0.05) and PGFza (P<0.001) in the BALF in the asthmatic mice. Conclusion Chloroquine can inhibit AHR in asthmatic mice and produce better anti-inflammatory effect when combined with dexamethasone for treatment of neutrophilic asthma.
Subjects: Medicine, Pharmacy >> Other Disciplines of Medicine and Pharmacology submitted time 2024-07-22
Abstract： Bone fracture is an important factor affecting the life quality and mortality of elderly individuals, and its pathogenesis involves the imbalance of bone metabolism maintained by osteoblasts (OB) and osteoclasts (OC). 99Tc-MDP is a drug for the targeted treatment of osteoporosis. While it can directly inhibit OC activity, there have been no in vivo data on its ability to induce OB activity. [Purpose]:This study aim to evaluate the effect of 99Tc-MDP on osteogenesis in the treatment of osteoporosis. [Methods]: In this study, a rat model of osteoporosis after ovariectomy were constructed, and the dynamic changes of osteoblast indexes after 99Tc-MDP treatment were detected at the cellular, metabolic, and genetic levels to evaluate the effect of 99Tc-MDP on osteogenesis in the treatment of osteoporosis. The rat model of osteoporosis can reflect the early process of osteoporosis formation, including calcium loss and bone mineral density decrease. [Results]: 99Tc-MDP effectively inhibited the osteoporosis process and reversed bone mineral density loss by inducing OB activity, achieving the suppression of bone decline at 4 weeks and returning to the preoperative level at 8 weeks. The OB activity induced by 99Tc-MDP was altered to similar levels in OB cells of normal rats, but there was no significant change in the expression of major bone-relatedgenes. The multifactor analysis suggested that IL-6 could be the key factor and monitoring index. [Conclusions]: 99Tc-MDP can stimulate OB activity as a powerful supplement to inhibiting OC activity, which is beneficial to the maintenance of OB/OC homeostasis.
Subjects: Biology >> Biophysics submitted time 2016-05-12
Cao, Wei
Zhang, Ran
Zhu, Xianbing
Mei, Lin
Chen, Hongbo
Zhang, Hongling
Huang, Laiqiang
Cao, Wei
Liu, Ying
Zhang, Ran
Wang, Teng
Zhu, Xianbing
Mei, Lin
Chen, Hongbo
Zhang, Hongling
Huang, Laiqiang
Cao, Wei
Liu, Ying
Zhang, Ran
Wang, Teng
Abstract： Tyrosine kinase inhibitors (TKIs) are mostly used in non-small cell lung cancer (NSCLC) treatment. Unfortunately, treatment with Gefitinib for a period of time will result in drug resistance and cause treatment failure in clinic. Therefore, exploring novel compounds to overcome this resistance is urgently required. Here we investigated the antitumor effect of homoharringtonine (HHT), a natural compound extracted from Cephalotaxus harringtonia, on Gefitinib-resistant NSCLC cell lines in vitro and in vivo. NCI-H1975 cells with EGFR T790M mutation are more sensitive to HHT treatment compared with that of A549 cells with wild type EGFR. HHT inhibited cells growth, cell viability and colony formation, as well as induced cell apoptosis through mitochondria pathway. Furthermore, we explored the mechanism of HHT inhibition on NSCLC cells. Higher level of interleukin-6 (IL-6) existed in lung cancer patients and mutant EGFR and TGF beta signal requires the upregulation of IL-6 through the gp130/JAK pathway to overactive STAT3, an oncogenic protein which has been considered as a potential target for cancer therapy. HHT reversiblely inhibited IL-6-induced STAT3 Tyrosine 705 phosphorylation and reduced anti-apoptotic proteins expression. Gefitinib-resistant NSCLC xenograft tests also confirmed the antitumor effect of HHT in vivo. Consequently, HHT has the potential in Gefitinib-resistant NSCLC treatment.
Peer Review Status:
Awaiting Review
Subjects: Biology >> Bioengineering submitted time 2018-10-26 Cooperative journals: 《中国生物工程杂志》
Abstract：目的：探讨微环境中钙周期素S100A6 是否通过影响巨噬细胞（macrophages, Mφ）进而促进结直肠癌（colorectal cancer, CRC）细胞的增殖及其机制。方法：制备（原核表达）并鉴定带GST（glutathione S-transferase，谷胱甘肽S-转移酶）标签的人重组S100A6蛋白(recombinant GST-hS100A6，rS100A6) 和对照蛋白GST；采用台盼兰计数、CCK8和结晶紫染色检测CRC细胞系HCT116的增殖能力；用定量实时聚合酶链反应检测Mφ中IL-6 mRNA水平；用Western blot检测Mφ中IL-6的蛋白水平、HCT116细胞中JAK2和STAT3及其磷酸化水平。 结果：（1）成功制备rS100A6和GST蛋白。（2）与经rS100A6处理的Mφ（即A6-Mφ）共培养后，HCT116细胞的增殖能力增强（P<0.05）；同时，HCT116细胞中的JAK2和STAT3水平无明显变化，但其磷酸化水平提高（P<0.05）。（3）A6-Mφ中，IL-6的mRNA和蛋白水平均升高（P<0.05）。（4）在HCT116与A6-Mφ的共培养体系中加入IL-6R封闭肽后，A6-Mφ促HCT116细胞的活力和增殖能力的作用被部分逆转（P<0.05）。 结论：微环境中的S100A6可通过上调巨噬细胞中IL-6的表达、进而激活HCT116细胞中IL-6/JAK2/STAT3信号通路来促进CRC细胞的增殖。
Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2017-12-07 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To observe the effect of anti-survivin oligonucleotides (ASODN) on the invasion and growth of peritoneally implanted ovarian cancer cell xenografts in nude mice. Methods Nude mouse models bearing peritoneally implanted ovarian cancer cell (SKOV3) xenografts were established and subjected to intraperitoneal injection of survivin ASODN or saline (control). The number and weight of the intraperitoneal xenografts were compared between the two groups. The expressions of interieukin (IL-6), signal transducer and activator of transcription3 (STAT3), phosphorylated STAT3 (p-STAT3), and survivin protein in the tumor tissues were detected with Western blotting in both groups. Results Compared with those in the control group, the number and weight of the intraperitoneal xenografts were significantly reduced in ASODN group (P<0.05). ASODN treatment also resulted in significantly lowered protein levels of IL-6, STAT3, p-STAT3, and survivin in the tumor tissues (P<0.05). Conclusion Survivin ASODN can suppress the invasion and migration capacity of ovarian cancer cells and inhibit peritoneal metastasis of the tumor in nude mice possibly though down-regulation of IL-6/ STAT3 signaling pathway.
Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2017-12-07 Cooperative journals: 《分子影像学杂志》
Abstract： Objective To evaluate the value of lipopolysaccharide (LPS) in invasive brain injury (TBI) inflammatory response(Inflammation). Methods Eighty-six patients with TBI in Third People's Hospital of Nanhai Foshan were enrolled.They weredivided into 3 groups according to the Glasgow coma scale (GCS) score, with mild group of 33 cases, moderate group of 24cases and severe group of 29 cases. Twenty-eight cases with health examination in the same period were selected as a controlgroup.The levels of nitric oxide (NO) in serum were detected by GREISS. The levels of TNF-α, IL-6, IL-1β and were measuredby ELISA. Results The levels of serum TNF-α were increased in the mild, moderate and severe groups, and the third day wasthe highest. The levels of serum TNF-α on the 5th and 7th day were gradually decreased and still higher than the controlgroup. The levels of serum IL-6 in the mild, moderate and severe groups were higher than those in the control group (P<0.05).The level of IL-6 in the mild and moderate group was significantly higher than that in the control group (r=0.925, P<0.05). Thelevels of serum IL-1β in the mild group, moderate group and severe group were higher than those in the control group, andthe increasement was significant on the third , fifth day (P<0.05). The severity of TBI was correlated with serum IL-1βconcentration (r=1.267, P<0.05). The levels of serum NO in the mild, moderate and severe groups were significantly higher thanthose in the control group (P<0.05), and serum NO levels on the third day was higher than that in the control group. NOconcentration was correlated with the severity of TBI (r=0.847, P<0.05). Conclusion The changes of TNF-α, IL-6, IL-1β and NOin serum are closely related to the degree of TBI. High NO concentration means a serious brain tissue injury and poorprognosis.
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