摘要：
This study explored the correlation among the expression, clinical significance, and prognosis of DJ-1 and RUNX3 in rectal cancer. Eighty-five cases of resected rectal cancer tissue were obtained from patients treated from June 2014 to June 2015. The expression of DJ-1 and RUNX3 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the expression of DJ-1 and RUNX3 protein was detected by immunohistochemistry. Their relationship to the clinicopathological features of the tumor was also analyzed. The correlation between the two proteins and survival prognosis [5-year disease-free survival (DES)] was analyzed. RT-PCR results showed that the DJ-1 mRNA expression of cancer tissue increased, whereas that of RUNX3 decreased. Immunohistochemical results showed that the positive rate of DJ-1 protein of cancer tissue increased (69.41% vs. 21.18%), whereas that of RUNX3 decreased (40.00% vs. 77,65 degrees 4 The positive expression of DJ-1 and RUNX3 was highly related to the cTNM staging of rectal cancer. Correlation analysis results showed a negative correlation between the genes in rectal cancer tissue. The follow-up records showed 5-year DFS data as follows: 50.00% for the DJ-1(+)/RUNX3(-) group, 57.14% for the DJ-1(-)/RUNX3(-) group, 71.43% for the DJ-1(+)/RUNX3(+) group, and 82.50% for the DJ-1(-)/RUNX3(+) group, suggesting that the 5-year DFS of the DJ-1(+) group was lower, whereas that of the RUNX3(+) group was higher. These results indicated that DJ-1 and RUNX3 were related to the occurrence, development, and progression of rectal cancer. Interestingly, there was a significant negative correlation between the genes, which was important for the treatment and prognosis of rectal cancer.
期刊：
OncoTargets and Therapy,2021年14:4047-4060 ISSN：1178-6930
通讯作者：
Guihua Wang<&wdkj&>Jinyue Hu
作者机构：
[Xia, Yuchen] Hunan Univ Chinese Med, Grad Sch, Changsha, Hunan, Peoples R China.;[Xia, Yuchen; Wang, Guihua] Univ South China, Changsha Cent Hosp, Dept Oncol, Changsha, Hunan, Peoples R China.;[Hu, Jinyue; Jiang, Binyuan; Jiang, Manli; Liu, Xueting] Univ South China, Changsha Cent Hosp, Med Res Ctr, Changsha 410004, Hunan, Peoples R China.;[Zhu, Demao; Zhao, Yan] Univ South China, Changsha Cent Hosp, Dept Pathol, Changsha, Hunan, Peoples R China.;[Song, Yinghui] Hunan Normal Univ, Hunan Prov Peoples Hosp, Dept Hepatobiliary Surg, Changsha, Hunan, Peoples R China.
通讯机构：
[Guihua Wang] D;[Jinyue Hu] M;Department of Oncology, Changsha Central Hospital, University of South China, Changsha, Hunan, People��s Republic of China<&wdkj&>Medical Research Center, Changsha Central Hospital, University of South China, Changsha, Hunan, People��s Republic of China
摘要：
Introduction: Glutathione reductase (GSR) provides reduced glutathione (GSH) to main-tain redox homeostasis. Inhibition of GSR disrupts this balance, resulting in cell damage, which benefits cancer therapy. However, the effect of GSR inhibition on the tumorigenicity of human cervical cancer is not fully understood. Materials and Methods: Tissue microarray analysis was employed to determine GSR expression in cervical cancer tissues by immunohistochemical staining. Cell death was measured with PI/FITC-annexin V staining. mRNA levels were measured via quantitative RT-PCR. Protein expression was measured by Western blotting and flow cytometry. STAT3 deletion was performed with CRISPR/Cas9 technology. GSR knockdown was achieved by RNA interference. Reactive oxygen species (ROS) levels were measured by DCF staining. GSR enzymatic activity was measured with a GSR assay kit. The effect of GSR inhibition on the growth of tumors formed by cervical cancer cells was investigated using a xenograft model. Results: The expression of GSR was increased in human cervical cancer tissues, as shown by immunohistochemical staining. GSR knockdown by RNA interference in human cervical cancer cell lines resulted in cell death, suggesting the ability of GSR to maintain cancer cell survival. The STAT3 inhibitor 6-nitrobenzo[b]thiophene 1,1-dioxide (Stattic) also inhibited the enzymatic activity of GSR and induced the death of cervical cancer cells. More importantly, Stattic decreased the growth of xenograft tumors formed by cervical cancer cells in nude mice. Mechanistically, tumor cell death induced by Stattic-mediated GSR inhibition was ROS-dependent, since the ROS scavengers GSH and N-acetyl cysteine (NAC) reversed the effect of Stattic. In contrast, pharmacological and molecular inhibition of STAT3 did not induce the death of cervical cancer cells, suggesting a STAT3-independent activity of Stattic. Conclusion: Stattic inhibits the enzymatic activity of GSR and induces STAT3-independent but ROS-dependent death of cervical cancer cells, suggesting its potential application as a therapeutic agent for human cervical cancers.
作者机构：
[Li, Lin; Hu, Zhi-xi; Hu, Si-yuan] Hunan Univ Chinese Med, Domest Class Discipline Construct Project Chinese, Changsha, Hunan, Peoples R China.;[Li, Lin; Hu, Zhi-xi] Hunan Univ Chinese Med, Inst Tradit Chinese Med Diagnost, Changsha, Hunan, Peoples R China.;[Zhong, Sen-jie; Cheng, Bin; Qiu, Hong] Hunan Univ Chinese Med, Postgrad Sch, Changsha, Hunan, Peoples R China.
通讯机构：
[Hu, Zhi-Xi] T;The Domestic First-class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China.;Institute of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China.
摘要：
The potential role of the gut microbiome (GM) in heart failure (HF) had recently been revealed. However, the underlying mechanisms of the GM and fecal metabolome in HF have not been characterized. The Dahl salt-sensitive rat model of hypertensive heart failure (H-HF) was used to study the clinical symptoms and characteristics. To elucidate the pathogenesis of HF, we combined 16S rRNA gene sequencing and metabolomics to analyze gut microbial compositions and fecal metabolomic profiles of rats with H-HF. PCoA of beta diversity shown that the gut microbiome composition profiles among the three groups were separated. Gut microbial composition was significantly altered in H-HF rats, the ratio of Firmicutes to Bacteroidetes(F/B) increased and the abundance of Muribaculaceae, Lachnospiraceae, and Lactobacillaceae decreased. Significantly altered levels of 17 genera and 35 metabolites were identified as the potential biomarker of H-HF. Correlation analysis revealed that specific altered genera were strongly correlated with changed fecal metabolites. The reduction in short-chain fatty acids (SCFA)-producing bacteria and trimethylamine N-oxide (TMAO) might be a notable characteristic for H-HF. This is the first study to characterize the fecal microbiome of hypertensive heart failure by integrating 16S rRNA gene sequencing and LC–MS-based metabolomics approaches. Collectively, the results suggesting changes of gut microbiome composition and metabolites are associated with hypertensive heart failure rats.
作者：
Yang Kongzhi;Song Kun;Guo Cuirong;Ding Ning;Li Changluo
期刊：
实用休克杂志(中英文),2021年5(06):375-384 ISSN：2096-4544
作者机构：
[Yang Kongzhi] Hunan university of Chinese Medicine,Graduate,choolChangsha,China;[Guo Cuirong; Ding Ning; Song Kun; Li Changluo] The Affiliated Changsha Central Hospital,Hengyang Medical School,University of South China,Changsha,China.
摘要：
Background A model which can early and sensitively identify poor clinical outcome in short-term and long-term could be a useful tool to help physicians to assess the severity of the dis-ease and early onset of therapeutic measures would be implemented in order to improve the prognosis of sepsis patients. This present study aimed to develop early predictive models for clinical outcomes based on a public database. Methods In the Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ)database,patients with severe sepsis or septic shock were included. Clinical variables were com-pared between survivor group and non-survivor group. Risk factors were identified by logistic regres-sion model. Results A total of 2057 patients with severe sepsis or septic shock were finally enrolled. Mortality in 30-day and 180-day were 35.39％ and 48.47％,respectively. Four independent factors including age,RDW,lactate and albumin for 30-day and 180-day mortality were identified in multiva-riate analysis. The accuracy of 30-day mortality model and 180-day mortality model were 0.702 and 0.716,respectively. The area under the receiver operating characteristic curves (AUCs)of two mod-els were 0.711 and 0.722,respectively.Conclusions In our study,a predictive model with four inde-pendent factors including age,RDW,lactate and albumin was performed by logistic regression,which could be applied for early identification in both 30-day and 180-day mortality in severe sepsis or septic shock.
