摘要：
Background: Ciliary neurotrophic factor (CNTF), which is a neural peptide, has been reported to confer cardioprotective effects. However, whether CNTF-based gene therapy could prevent cardiac remodelling remains incompletely clear. In this study, we used adeno-associated viral vector serotype 9 (AAV9)-based cardiac gene therapy to test the effects of CNTF overexpression on adverse ventricular remodelling in angiotensin II (Ang II)-infused mice. Methods: First, AAV9-EGFP and AAV9-CNTF constructs were generated with virus concentration at 5 x 10(12) vg/ml. Next, postnatal (P3-P10) mice with C57BL/6J background were administered with 5 x 10(11) vg of AAV9 recombinant genome diluted in 50 ml of saline, and delivered through intraperitoneal injection. Implantation of osmotic minipumps was performed in 8-week-old male mice and human Ang II solution was administrated in the mice subcutaneously for 14 days through the pumps. Finally, we evaluated the effects of CNTF overexpression on mouse cardiac function, hypertrophy and fibrosis, as well as investigated the possible mechanisms. Results: Our data showed that CNTF overexpression in mouse cardiomyocytes prevents cardiac hypertrophy and fibrosis induced by chronic Ang II stimulation. Mechanistic study found that CNTF over expression upregulated NFE2-related factor 2 (Nrf2) antioxidant pathway, coupled with decreased ROS level in the cardiac tissues. Additionally, inflammatory cytokines were found to be reduced upon cardiac CNTF overexpression in response to chronic Ang II stimulation. Conclusions: Altogether, these results provide further evidence that CNTF can alleviate the condition of cardiac remodelling induced by chronic Ang II stimulation. Therefore, our results suggest a potential therapeutic role of CNTF in cardiac pathological remodelling. (c) 2021 Elsevier Inc. All rights reserved.
摘要：
PURPOSE: To evaluate S1AI-S4AI screw channels with three-dimensional digital technology simulation analysis and to study the feasibility and applicable features of sacral alar-iliac screw fixation in adults. MATERIALS AND METHODS: Forty (20 men and 20 women) normal adult's pelvic CT scan data sets were selected to reconstruct the three-dimensional pelvic model. The ideal S1AI-S4AI screw channels were simulated, followed by precise measurement of their parameters. RESULTS: The results showed that there were no significant differences in the transverse angles, sagittal angles, radiuses of the maximal inscribed circles, or lengths of the screw channels in S1AI-S2AI screws between genders (P > 0.05). In contrast, the radiuses of the maximal inscribed circles on the left and right, respectively, were 5.93 +/- 1.02 mm and 5.92 +/- 1.04 mm in males and 4.64 +/- 0.98 mm and 4.59 +/- 0.95 mm in females, and there was a significant difference in S3AI screws between genders (P < 0.05). With a radius of 2.50 mm considered to be standard, there were 25 cases (62.5%) with an S4AI screw channel radius </= 2.50 mm in 40 adults, and 15 cases (37.5%; 9 males and 6 females) with a radius > 2.50 mm. Furthermore, the transverse angles, the sagittal angles, the lengths of the screw channels, and the radiuses of the maximal inscribed circles were significantly different between genders in 15 cases (P < 0.05). CONCLUSION: Only one maximum ideal screw can be placed on one side at a time. With a radius of 2.50 mm considered to be standard, it is feasible to place S1AI-S3AI screws with a radius > 2.50 mm in the entire adult population and S4AI screws with a radius > 2.50 mm in some of the adult population. Furthermore, preoperative three-dimensional reconstruction and three-matic research software can effectively simulate the sacral alar-iliac screw channels, and they can provide accurate data for clinical applications.
摘要：
Gastric cancer (GC) is the fifth most common primary malignancy in humans. Rho GDP dissociation inhibitor 2 (RhoGDI2) is overexpressed in multiple cancer types, but the role of RhoGDI2 in GC has not been elucidated. This study aims to determine the level of RhoGDI2 in GC and to confirm the effect of its inhibition or overexpression on GC cell migration, invasion and chemosensitivity. RhoGDI2 level is significantly enhanced in human GC tissue samples in comparison with normal gastric epithelium and corresponding para-cancerous samples. The expression of RhoGDI2 is correlated with clinicopathological parameters and prognosis. Transfection in combination with miRNA targeting of RhoGDI2 in GC cell lines remarkably downregulates GC cell migration and invasion and reduces the mRNA levels of Rac1, Pak1 and LIMK1. The inhibition of RhoGDI2 downregulates GC cell migration and invasion by attenuating the EMT cascade via the Rac1/Pak1/LIMK1 pathway. Knockdown of RhoGDI2 is a potential therapeutic strategy for GC.
作者机构：
[夏红; 苏琦; 刘芳; Zeng X.] Cancer Research Institute, Hunan Province Key Lab of Cancer Cellular and Molecular Pathology, Center for Gastric Cancer Research of Hunan Province, University of South China, Hengyang, Hunan, 421001, China;Dept of Pathology, Affiliated Xiangtan Hospital, University of South China, Xiangtan, Hunan, 411101, China;Dept of Basic Medicine, Yongzhou Vocational Technical College, Yongzhou, Hunan, 425100, China;Dept of Pathology, Second Affiliated Hospital, University of South China, Hengyang, Hunan, 421001, China;[唐仪] Cancer Research Institute, Hunan Province Key Lab of Cancer Cellular and Molecular Pathology, Center for Gastric Cancer Research of Hunan Province, University of South China, Hengyang, Hunan, 421001, China, Dept of Pathology, Affiliated Xiangtan Hospital, University of South China, Xiangtan, Hunan, 411101, China
作者机构：
[Wang, Siyang; Liu, Zhigang; Liu, Qiaodan; Yao, Jijin] Sun Yat Sen Univ, Phase 1 Clin Trial Ward, Dept Head & Neck Oncol, Canc Ctr,Affiliated Hosp 5, Zhuhai 519001, Peoples R China.;[Zhou, Jiao; Liu, Guiyun; Xu, Chenyang; Liu, Fengzin; Jiang, Rong] Cent S Univ, Xiangya Sch Med, Affiliated Canc Hosp, Dept Radiat Oncol,Hunan Canc Hosp, Changsha 410000, Hunan, Peoples R China.;[Zhou, Jiao; Liu, Guiyun; Xu, Chenyang; Liu, Fengzin; Jiang, Rong] Univ South China, Dept Clin Med, Hengyang 421000, Peoples R China.;[Jiang, Wen] Univ Texas Southwestern Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA.
通讯机构：
[Liu, Zhigang] S;Sun Yat Sen Univ, Phase 1 Clin Trial Ward, Dept Head & Neck Oncol, Canc Ctr,Affiliated Hosp 5, Zhuhai 519001, Peoples R China.
摘要：
Nasopharyngeal carcinoma (NPC) is endemic in southern China. Due to the unique anatomical and biological properties of NPCs, radiotherapy or combined modality based on radiotherapy is an effective treatment option. Helical tomotherapy (HT) is an emerging intensity modulated radiotherapy technology. The advantages of dose homogeneity, steepness of dose gradient, and protection of normal organs are reflected in the treatment of head and neck cancers. We present the preliminary (2-year) clinical outcomes of HT in 85 patients with locally advanced NPC (LA-NPC). Of these patients, 3 patients (3.5%) experienced treatment interruption due to severe pulmonary infection, and 82 (96.5%) completed radiation treatments. The 2-year estimate of progression-free survival, local relapse-free survival, nodal relapse-free survival, distant metastases-free survival, and overall survival rate were 90%, 96.3%, 98.8%, 96.3%, and 96.3%, respectively. Among the three patients that died, one had stage III disease and died from fatal nasopharyngeal bleeding after radiotherapy, while the other two patients succumbed to local recurrence. Our experience suggests that HT can achieve promising disease control and survival in the treatment of LA-NPC patients with mild acute and late toxicity profiles.
摘要：
Retinoid-related orphan receptor alpha (RORalpha) is involved in tumor development. However, the mechanisms underlying RORalpha inhibiting epithelial-to-mesenchymal transition (EMT) and invasion are poorly understood in gastric cancer (GC). This study revealed that the decreased expression of RORalpha is associated with GC development, progression, and prognosis. RORalpha suppressed cell proliferation, EMT, and invasion in GC cells through inhibition of the Wnt/beta-catenin pathway. RORalpha overexpression resulted in the decreased Wnt1 expression and the increased RORalpha interaction with beta-catenin, which could lead to the decreased intranuclear beta-catenin and p-beta-catenin levels, concomitant with downregulated T-cell factor-4 (TCF-4) expression and the promoter activity of c-Myc. The inhibition of Wnt/beta-catenin pathway was coupled with the reduced expression of Axin, c-Myc, and c-Jun. RORalpha downregulated vimentin and Snail and upregulated E-cadherin protein levels in vitro and in vivo. Inversely, knockdown of RORalpha attenuated its inhibitory effects on Wnt/beta-catenin pathway and its downstream gene expression, facilitating cell proliferation, EMT, migration, and invasion in GC cells. Therefore, RORalpha could play a crucial role in repressing GC cell proliferation, EMT, and invasion via downregulating Wnt/beta-catenin pathway.
作者机构：
[吉晓霞] Department of Pathology,Yuncheng Muinicipal Central Hospital , Yuncheng 044000, Shanxi Province, China;[何洁; 易岚; 吉晓霞; 谭晖; 夏红; 刘芳] Key Laboratory of Cancer And Moleculay Pathology, Institute of Oncology, University of South China, Hengyang 421001, Hunan Province, China;[苏琦] Key Laboratory of Cancer And Moleculay Pathology, Institute of Oncology, University of South China, Hengyang 421001, Hunan Province, China. E-mail: suqi1945@163.com
摘要：
Transforming growth factor-beta 1 (TGF-beta 1) has been demonstrated to promote epithelial-mesenchymal transition (EMT), invasion and proliferation in tumors via the activation of Rac1 and beta-catenin signaling pathways. The present study investigated the effects of diallyl disulfide (DADS) on TGF-beta 1-induced EMT, invasion and growth of gastric cancer cells. TGF-beta 1 treatment augmented EMT and invasion, concomitantly with increased expression of TGF-beta 1, Rac1 and beta-catenin in gastric cancer cells. DADS downregulated the expression levels of TGF-beta 1, Rac1 and beta-catenin. DADS, TGF-beta 1 receptor inhibitor as well as Rac1 inhibitor antagonized the upregulation of the TGF-beta 1-induced expression of these genes, abolishing the enhanced effects of TGF-beta 1 on EMT and invasion. Blocking the TGF-beta 1 receptor through inhibition resulted in the decreased expression of Rac1 and beta-catenin. Rac1 inhibitor reduced the TGF-beta 1-induced beta-catenin expression. In addition, DADS and the aforementioned inhibitors attenuated the TGF-beta 1-induced tumor growth and the expression changes of E-cadherin, vimentin, Ki-67 and CD34 in nude mice. These data indicated that the blockage of TGF-beta 1/Rac1 signaling by DADS may be responsible for the suppression of EMT, invasion and tumor growth in gastric cancer.
摘要：
Diallyl disulfide (DADS) is a primary component of garlic, which has chemopreventive potential. We previously found that moderate doses (15-120 μM) of DADS induced apoptosis and G2/M phase cell cycle arrest. In this study, we observed the effect of low doses (8 μM) of DADS on human leukemia HL-60 cells. We found that DADS could inhibit proliferation, migration and invasion in HL-60 cells, and arrested cells at G0/G1 stage. Then, cell differentiation was displayed by morphologic observation, NBT reduction activity and CD11b evaluation of cytometric flow. It showed that DADS induced differentiation, reduced the ability of NBT and increased CD11b expression. Likewise, DADS inhibited xenograft tumor growth and induced differentiation in vivo. In order to make sure how DADS induced differentiation, we compared the protein expression profile of DADS-treated cells with that of untreated control. Using high resolution mass spectrometry, we identified 18 differentially expressed proteins after treatment with DADS, including four upregulated and 14 downregulated proteins. RT-PCR and western blot assay showed that DJ-1, cofilin 1, RhoGDP dissociation inhibitor 2 (RhoGDI2), Calreticulin (CTR) and PCNA were decreased by DADS. These data suggest that the effects of DADS on leukemia may be due to multiple targets for intervention.
作者机构：
[Zeng X.; 夏红; 苏波; 刘芳; 苏琦] Cancer Research Institute, Center for Gastric Cancer Research of Hunan Province, Key Lab of Cancer Cellular and Molecular Pathology, Hunan Provincial University, University of South China, Hengyang Hunan, 421001, China;Dept of Basic Medicine, Yongzhou Vocational Technical College, Yongzhou Hunan, 425100, China;Dept of Pathology, Affiliated Xiangtan Hospital, University of South China, Xiangtan Hunan, 411101, China;Dept of Pathology, Second Affiliated Hospital, University of South China, Hengyang Hunan, 421001, China;[唐云云] Cancer Research Institute, Center for Gastric Cancer Research of Hunan Province, Key Lab of Cancer Cellular and Molecular Pathology, Hunan Provincial University, University of South China, Hengyang Hunan, 421001, China, Dept of Basic Medicine, Yongzhou Vocational Technical College, Yongzhou Hunan, 425100, China
摘要：
Objective To evaluate the protective effect of estrogen on spinal cord ischemia-reperfusion injury inrabbits and its mechanism.Methods According to a random number table method,adult New Zealand rabbits weredivided into A-E five groups with9in each group.In the rabbits of group A,infrarenal aorta was clamped for20min and then blood circulation was restored(reperfusion).The rabbits of group B received the same anesthesia andsurgery as group A,but no ischemia-reperfusion injury.The rabbits of groups C,D and E had injection of estrogen200,400and800滋g/kg respectively through ear veins when reperfusion started.The neurological function of thelower extremities was scored according to Tarlov law48h after reperfusion.Then hematoxylin-eosin staining was usedfor pathological analysis of spinal cord.Results The neurological function scores of the groups C,D and E weresignificantly higher than those of the group A(<0.05).Histopathological study showed apoptosis and markednecrosis of the motor neurons in the anterior horn of the spinal cord.The number of anterior horn motor neurons in thegroup A was significantly smaller than that of the estrogen groups(<0.05).Conclusions Estrogen can significantlyimprove the neurological function of the lower limbs of rabbits with spinal cord ischemia and reperfusion,increase thenumber of normal motor neurons in the anterior horn of the spinal cord,and reduce ischemia-reperfusion injury.
作者机构：
南华大学附属第二医院病理科,湖南 衡阳 421001;南华大学肿瘤研究所,湖南省胃癌研究中心,湖南省高校肿瘤细胞与分子病理学重点实验室,湖南 衡阳 421001;海南省妇幼保健院,海南 海口 570206;[夏红; Zeng X.; 苏琦; 刘芳; 向姝霖; 凌晖; 苏波] Cancer Research Institute, Center for Gastric Cancer Research of Hunan Province, Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan, Provincial University, University of South China, Hengyang, 421001, China;[苏坚] Dept of Pathology, Second Affiliated Hospital, University of South China, Hengyang Hunan, 421001, China, Cancer Research Institute, Center for Gastric Cancer Research of Hunan Province, Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan, Provincial University, University of South China, Hengyang, 421001, China
