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992.
993.
Dafei Chai Dong Qiu Zichun Zhang Shang Yuchen Shi Gang Wang Lin Fang Huizhong Li Hailong Li Hui Tian Junnian Zheng 《Journal of cellular and molecular medicine》2020,24(18):10744-10755
Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIXpromotor)‐controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIXpromotor‐AIM2 adenoviruses (Ad‐CAIXpromotor‐AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad‐CAIXpromotor, Ad‐CAIXpromotor‐AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786‐O cells or OSRC‐2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC‐2‐xenograft mice. The tumour growth was remarkably inhibited in Ad‐CAIXpromotor‐AIM2‐treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD‐CMK resulted in the reduction of anti‐tumour activity by Ad‐CAIXpromotor‐AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad‐CAIXpromotor‐AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour‐specific Ad‐CAIXpromotor‐AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2‐based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours. 相似文献
994.
995.
Min Lin Li Ye Yang Dong De Xie Jiang Tao Chen Santiago-m Monte Nguba Carlos Sala Ehapo Xiao Fen Zhan Juan Urbano Monsuy Eyi Rocio Apicante Matesa Maximo Miko Ondo Obono Hui Yang Hui Tian Yang Ji Dong Cheng 《PloS one》2015,10(4)
Background
Glucose-6-phosphate dehydrogenase (G6PD) deficiency and hemoglobinopathies were the inherited conditions found mostly in African. However, few epidemiological data of these disorders was reported in Equatorial Guinea (EQG). This study aimed to assess the prevalence and healthy effects of G6PD deficiency and hemoglobinopathies among the people on malaria endemic Bioko Island, EQG.Materials and Methods
Blood samples from 4,144 unrelated subjects were analyzed for G6PD deficieny by fluorescence spot test (FST), high-resolution melting assay and PCR-DNA sequencing. In addition, 1,186 samples were randomly selected from the 4,144 subjects for detection of hemoglobin S (HbS), HbC, and α-thalassemia deletion by complete blood count, PCR-DNA sequencing and reverse dot blot (RDB).Results
The prevalence of malaria and anemia was 12.6% (522/4,144) and 32.8% (389/1,186), respectively. Overall, 8.7% subjects (359/4,144) were G6PD-deficient by FST, including 9.0% (249/2,758) males and 7.9% (110/1,386) females. Among the 359 G6PD-deficient individuals molecularly studied, the G6PD A- (G202A/A376G) were detected in 356 cases (99.2%), G6PD Betica (T968C/A376G) in 3 cases. Among the 1,186 subjects, 201 cases were HbS heterozygotes, 35 cases were HbC heterozygotes, and 2 cases were HbCS double heterozygotes; 452 cases showed heterozygous α-thalassemia 3.7 kb deletion (-α3.7 kb deletion) and 85 homozygous - α3.7 kb deletion. The overall allele frequencies were HbS 17.1% (203/1186); HbC, 3.1% (37/1186); and –α3.7 kb deletion 52.4% (622/1186), respectively.Conclusions
High G6PD deficiency in this population indicate that diagnosis and management of G6PD deficiency is necessary on Bioko Island. Obligatory newborn screening, prenatal screening and counseling for these genetic disorders, especially HbS, are needed on the island. 相似文献996.
Xiaoxi B. Lin Christopher T. Lohans Rebbeca Duar Jinshui Zheng John C. Vederas Jens Walter Michael G?nzle 《Applied and environmental microbiology》2015,81(6):2032-2041
Reutericyclin is a unique antimicrobial tetramic acid produced by some strains of Lactobacillus reuteri. This study aimed to identify the genetic determinants of reutericyclin biosynthesis. Comparisons of the genomes of reutericyclin-producing L. reuteri strains with those of non-reutericyclin-producing strains identified a genomic island of 14 open reading frames (ORFs) including genes coding for a nonribosomal peptide synthetase (NRPS), a polyketide synthase (PKS), homologues of PhlA, PhlB, and PhlC, and putative transport and regulatory proteins. The protein encoded by rtcN is composed of a condensation domain, an adenylation domain likely specific for d-leucine, and a thiolation domain. rtcK codes for a PKS that is composed of a ketosynthase domain, an acyl-carrier protein domain, and a thioesterase domain. The products of rtcA, rtcB, and rtcC are homologous to the diacetylphloroglucinol-biosynthetic proteins PhlABC and may acetylate the tetramic acid moiety produced by RtcN and RtcK, forming reutericyclin. Deletion of rtcN or rtcABC in L. reuteri TMW1.656 abrogated reutericyclin production but did not affect resistance to reutericyclin. Genes coding for transport and regulatory proteins could be deleted only in the reutericyclin-negative L. reuteri strain TMW1.656ΔrtcN, and these deletions eliminated reutericyclin resistance. The genomic analyses suggest that the reutericyclin genomic island was horizontally acquired from an unknown source during a unique event. The combination of PhlABC homologues with both an NRPS and a PKS has also been identified in the lactic acid bacteria Streptococcus mutans and Lactobacillus plantarum, suggesting that the genes in these organisms and those in L. reuteri share an evolutionary origin. 相似文献
997.
Lin Ding An Song Meng Dai Min Xu Wanwan Sun Baihui Xu Jichao Sun Tiange Wang Yu Xu Jieli Lu Weiqing Wang Yufang Bi Guang Ning 《Journal of lipid research》2015,56(4):920-926
Lipoprotein (a) [Lp(a)], an LDL-like particle, has been proposed as a causal risk factor for CVD among general populations. Meanwhile, both serum Lp(a) and diabetes increase the risk of CVD. However, the relationship between serum Lp(a) and T2D is poorly characterized, especially in the Asian population. Therefore, we conducted a cross-sectional study in 10,122 participants aged 40 years or older in Jiading District, Shanghai, China. Our study found that the prevalence of T2D was decreased from 20.9% to 15.0% from the lowest quartile to the highest quartile of serum Lp(a) concentrations (P for trend <0.0001). Logistic regression analyses showed that the odds ratios and 95% confidence intervals of prevalent T2D for quartiles 2–4 versus quartile 1 were 0.86 (0.73–1.01), 0.88 (0.75–1.04), and 0.76 (0.64–0.90) (P for trend = 0.0002), after adjustment for traditional confounding factors. Moreover, the risks for prevalent prediabetes, insulin resistance, and hyperinsulinemia were also decreased from the lowest to the top quartile. This inverse association between serum Lp(a) and T2D was not appreciably changed after we adjusted hypoglycemic medications or excluded the subjects with hypoglycemic and/or lipid-lowering agents and/or a history of self-reported CVD. 相似文献
998.
Chunyan Liu Wenjuan Mei Juan Tang Qiongjing Yuan Ling Huang Miaomiao Lu Lin Wu Zhangzhe Peng Jie Meng Huixiang Yang Hong Shen Ben Lv Gaoyun Hu Lijian Tao 《PloS one》2015,10(6)
Background
Inflammation has a crucial role in renal interstitial fibrosis, which is the common pathway of chronic kidney diseases. Mefunidone (MFD) is a new compound which could effectively inhibit the proliferation of renal fibroblasts in vitro. However, the overall effect of Mefunidone in renal fibrosis remains unknown.Methods
Sprague-Dawley rats were randomly divided intro 6 groups: sham operation, unilateral ureteral obstruction (UUO), UUO/Mefunidone (25, 50, 100mg/kg/day) and UUO/PFD (500mg/kg/day). The rats were sacrificed respectively on days 3, 7, and 14 after the operation. Tubulointerstitial injury index, interstitial collagen deposition, expression of fibronectin (FN), α-smooth muscle actin (α-SMA), type I and III collagen and the number of CD3+ and CD68+ cells were determined. The expressions of proinflammatory cytokines, p-ERK, p-IκB, and p-STAT3 were measured in human renal proximal tubular epithelial cells of HK-2 or macrophages.Results
Mefunidone treatment significantly attenuated tubulointerstitial injury, interstitial collagen deposition, expression of FN, α-SMA, type I and III collagen in the obstructive kidneys, which correlated with significantly reduced the number of T cells and macrophages in the obstructive kidneys. Mechanistically, Mefunidone significantly inhibited tumor necrosis factor-α (TNF-α-) or lipopolysaccharide (LPS)-induced production of proinflammatory cytokines. This effect is possibly due to the inhibition of phosphorylation of ERK, IκB, and STAT3.Conclusion
Mefunidone treatment attenuated tubulointerstitial fibrosis in a rat model of UUO, at least in part, through inhibition of inflammation. 相似文献999.
Li-Na Liao Chia-Ing Li Chiu-Shong Liu Chiu-Ching Huang Wen-Yuan Lin Jen-Huai Chiang Cheng-Chieh Lin Tsai-Chung Li 《PloS one》2015,10(6)
Background
Whether HbA1c is a predictor of end-stage renal disease (ESRD) in type 2 diabetes patients remains unclear. This study evaluated relationship between HbA1c and ESRD in Chinese patients with type 2 diabetes.Methods
Patients aged ≥ 30 years who were free of ESRD (n = 51 681) were included from National Diabetes Care Management Program from 2002–2003. Extended Cox proportional hazard model with competing risk of death served to evaluate association between HbA1c level and ESRD.Results
A total of 2613 (5.06%) people developed ESRD during a follow-up period of 8.1 years. Overall incidence rate of ESRD was 6.26 per 1000 person-years. Patients with high levels of HbA1c had a high incidence rate of ESRD, from 4.29 for HbA1c of 6.0%–6.9% to 10.33 for HbA1c ≥ 10.0% per 1000 person-years. Patients with HbA1c < 6.0% particularly had a slightly higher ESRD incidence (4.34 per 1000 person-years) than those with HbA1c of 6.0%–6.9%. A J-shaped relationship between HbA1c level and ESRD risk was observed. After adjustment, patients with HbA1c < 6.0% and ≥ 10.0% exhibited an increased risk of ESRD (HR: 1.99, 95% CI: 1.62–2.44; HR: 4.42, 95% CI: 3.80–5.14, respectively) compared with those with HbA1c of 6.0%–6.9%.Conclusions
Diabetes care has focused on preventing hyperglycemia, but not hypoglycemia. Our study revealed that HbA1c level ≥ 7.0% was linked with increased ESRD risk in type 2 diabetes patients, and that HbA1c < 6.0% also had the potential to increase ESRD risk. Our study provides epidemiological evidence that appropriate glycemic control is essential for diabetes care to meet HbA1c targets and improve outcomes without increasing the risk to this population. Clinicians need to pay attention to HbA1c results on diabetic nephropathy. 相似文献1000.