Caveolin-1 in skin aging – From innocent bystander to major contributor

Caveolin-1 (Cav-1) appears to be both a pathophysiological contributor and a target in different inflammatory and hyperproliferative skin conditions as well as in skin aging. Skin fibroblasts demonstrate an up-regulation of Cav-1 expression both in chronological and UV-induced aging, and such an up-regulation was observed both in vitro and in vivo. Typical alterations in aging skin involve a reduction of the dermis thickness, a significant expansion of the dermal white adipose tissue as well as modifications of the content and distribution of hyaluronan, impairment of autophagic flux, a reduction of collagen expression and an increase in tissue inflammation. All of these phenomena can be connected with changes in Cav-1 expression in the aging skin. Modified expression of Cav-1 can also significantly influence the mechanical properties of individual skin layers, thus changing the total mechanical stability of the layered composite skin/WAT, leading to typical structural modifications of the skin surface in the aging skin. Selective reduction of Cav-1 expression has the potential to exert anti-aging effects on the skin.     

In silico repurposing the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing clear cell renal carcinoma

The pituitary tumor-transforming gene 1 (PTTG1), also known as Securin, is considered an oncogene. This study aimed to investigate the role of PTTG1 in clear cell renal cell carcinoma (ccRCC) using in silico bioinformatics approaches. A pan-cancer analysis using The Cancer Genome Atlas (TCGA) data indicated that among all cancer types copy number amplification of PTTG1 gene was most frequently found in ccRCC. However, amplification of PTTG1 gene copy number did not correlate with the increase of mRNA level in ccRCC, and did not predict the patients' overall survival. Instead, ccRCC was correlated with overexpression of PTTG1 mRNA, and its expression level was stage-dependent increased in cancer patients. An outlier analysis using the Oncomine database suggested that PTTG1 mRNA expression served as a good biomarker for ccRCC. Pathway analysis for upregulated genes enriched in PTTG1-high expressing ccRCC patients found that PTTG1 overexpression was associated with mitotic defects. Mining drug sensitivity data using the Cancer Therapeutics Response Portal (CTRP) discovered that PTTG1-high expressing ccRCC cell lines were susceptible to a Rac1 (Ras-related C3 botulinum toxin substrate 1) inhibitor NSC23766. Therefore, this study provides an in silico insight into the role of PTTG1 in ccRCC, and repurposes the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing ccRCC.     

Inhibition of PRRX2 suppressed colon cancer liver metastasis via inactivation of Wnt/β-catenin signaling pathway

The aim of this study was to investigate whether PRRX2 may regulate the liver metastasis of colon cancer via the Wnt/β-catenin signaling pathway. PRRX2 and β-catenin in patients with the liver metastases of colon cancer was detected by immunochemistry. Colon cancer cells (CT-26 and CMT93) were divided into Normal, si-Ctrl, si-PRRX2 and si-PRRX2 +LiCl groups. Cell invasive and migrating abilities and the related proteins were detected. Liver-metastatic mice model was constructed consisting of Normal, NC shRNA and PRRX2 shRNA groups to examine the function of PRRX2 shRNA on liver metastasis. We found that PRRX2 and β-catenin positive rate was elevated in colon cancer tissues, especially in those tissues with liver metastasis, and there was a close relation between PRRX2 and the clinical staging, lymph node metastasis and numbers of liver metastases of colon cancer patients with liver metastasis. In vitro, the invasive and migrating abilities of CT-26 and CMT93 cells decreased apparently in the si-PRRX2 group, with down-regulation of PRRX2, p-GSK3β^Ser9/GSK3β, nucleus and cytoplasm β-catenin, TCF4 and Vimentin but up-regulation of E-cadherin. However, LiCl, the Wnt/β-catenin pathway activator, can reverse the inhibitory effect of si-PRRX2 on invasive and migrating ability of colon cancer cells. In vivo, the volume and weight of transplanted tumor and the number of liver metastases in the PRRX2 shRNA group were significantly reduced, with the similar protein expression patterns as in vitro. In a word, PRRX2 inhibition may reduce invasive and migrating abilities to hinder epithelial-mesenchymal transition (EMT), and suppress colon cancer liver metastasis through inactivation of Wnt/β-catenin pathway.     

MicroRNA-301b-3p accelerates the growth of gastric cancer cells by targeting zinc finger and BTB domain containing 4

MicroRNAs (miRNAs) have been found to be aberrantly expressed and exert essential roles in the tumorigenesis and progression of gastric cancer (GC). miR-301b-3p has been recognized as a cancer-related miRNA in lung cancer, bladder cancer and hepatocellular carcinoma. However, the function of miR-301b-3p in GC progression and its underlying mechanism have not been studied yet. In this study, we found that miR-301b-3p expression was up-regulated in GC tissues compared to adjacent noncancerous tissues. Furthermore, the elevated levels of miR-301b-3p were detected in GC cell lines (SGC-7901, AGS, MKN-45 and MGC-803) as compared with GES-1 cells. Interestingly, GC tissues from patients with tumor size ≥ 5 cm and advanced tumor stages showed obvious higher levels of miR-301b-3p compared to matched controls. Functionally, miR-301b-3p knockdown prominently inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in MGC-803 cells. Meanwhile, ectopic expression of miR-301b-3p conversely regulated these biological behaviors of MKN-45 cells. Next, we found that miR-301b-3p knockdown increased, whereas miR-301b-3p overexpression reduced the expression of zinc finger and BTB domain containing 4 (ZBTB4) in GC cells. Accordingly, luciferase reporter assay identified ZBTB4 as a direct target of miR-301b-3p. ZBTB4 overexpression markedly restrained the growth of MGC-803 cells. More importantly, ZBTB4 silencing partially reversed miR-301b-3p knockdown-induced tumor suppressive effects on MGC-803 cells. In conclusion, we firstly revealed that miR-301-3p was highly expressed in GC and contributed to tumor progression via attenuating ZBTB4, which might provide a novel molecular-targeted strategy for GC treatment.     

Sinonasal glomangiopericytoma: A clinicopathologic study

Sinonasal glomangiopericytoma (SNGP) is a neoplasm arising in the nasal cavity and paranasal sinuses that shows perivascular myoid differentiation. The diagnosis of SNGP may be diagnostically challenging due to a large number of potential mimics. In the present study, we sought to characterize the histological and molecular features of six cases of SNGP found in prior surgical pathology records over a 15-year period. The average age at diagnosis was 48.5 years (range: 31–78 years), and the male-to-female ratio was 1:1. Imaging studies in all six cases demonstrated avidly enhancing, lobulated soft tissue masses in the nasal cavity, extending into the sinuses and nasopharynx. Histologically, the tumors were unencapsulated and composed of a proliferation of closely packed, bland, and uniform spindle cells growing deep to an intact surface respiratory epithelium. The cells were separated by a distinctive vascular network ranging from capillaries to large vascular spaces. All cases demonstrated strong positivity for smooth muscle actin, cyclin D1, CD99, and β-catenin (100%). Targeted sequencing revealed recurrent CTNNB1 missense mutations in all cases tested. Additionally, TLE1 was positive in all cases which has not been previously reported. No tested cases harbored SS18 translocations. We found that while no single marker resolves immunohistochemical overlap between SNGP and its histologic mimics, an extended immunohistochemical panel that includes β-catenin, cyclin D1, STAT6, smooth muscle actin, pan-cytokeratin cocktails, S100, and SOX10 helps to support the diagnosis of SNGP in diagnostically challenging cases without the need for molecular studies.     

耳穴贴压联合中医饮食调护对糖尿病肾病患者的影响

目的:观察耳穴贴压联合中医饮食调护对糖尿病肾病患者的影响。方法:将糖尿病肾病患者60例按随机数字表法分成2组,对照组30例患者采用耳穴贴压治疗,观察组30例患者采用耳穴贴压联合中医饮食调护治疗。对比2组患者治疗前后肾功能指标、血清糖化血红蛋白、尿微量白蛋白、24h尿蛋白定量变化和肾小管损伤情况。结果:2组治疗后,血尿素氮(BUN)、内生肌酐清除率(CCr)、24 h尿白蛋白排泄率(UAE)和血肌酐(SCr)水平均明显优于治疗前,差异有统计学意义(P<0.05);治疗后,观察组肾功能指标BUN、CCr、UAE低于对照组,SCr则有所提高,差异有统计学意义(P<0.05)。2组患者治疗后,尿蛋白定量、尿微量白蛋白和血清糖化血红蛋白水平均明显优于治疗前,差异有统计学意义(P<0.05);观察组治疗后尿蛋白、尿微量白蛋白、血清糖化血红蛋白指标低于对照组,差异有统计学意义(P<0.05)。2组患者治疗后,β2-微球蛋白(β2-MG)和N-乙酰-β-D-氨基葡萄糖苷酶(NAG)水平均明显优于治疗前,差异有统计学意义(P<0.05);观察组治疗后肾小管损伤指标β2-MG、NAG低于对照组,差异有统计学意义(P<0.05)。结论:耳穴贴压联合中医饮食调护在糖尿病肾病患者中疗效明确,可改善肾功能指标,减轻肾小管损伤,改善临床症状。     

和解汤联合耳穴贴压治疗少阳郁热型颈性眩晕疗效研究

目的:观察和解汤联合耳穴贴压治疗少阳郁热型颈性眩晕的疗效与安全性。方法:选取我院门诊部诊治的少阳郁热型颈性眩晕患者86例为研究对象,应用随机数字表以简单随机分组法分为观察组、对照组各43例,对照组予以常规西药治疗,观察组在此基础上采用和解汤联合耳穴贴压治疗,比较两组治疗有效率、治疗前后颈性眩晕症状与功能(ESOV)评分、彩色多普勒超声(TCD)下椎基底动脉血流动力学指标、血清相关指标[白介素-1β(IL-1β)、白介素-6(IL-6)、内皮素-1(ET-1)]、不良反应发生率。结果:观察组治疗有效率为95.35%,较对照组的81.40%高(P<0.05)。观察组治疗2周、治疗4周ESOV评分分别为(22.18±2.47)分、(25.13±2.56)分,高于对照组的(20.45±2.29)分、(22.76±2.35)分(P<0.05)。观察组治疗结束后左椎动脉、右椎动脉、基底动脉血流速度为(20.15±2.17)cm/s、(19.75±1.98)cm/s、(20.49±2.17)cm/s,均高于对照组的(18.96±1.93)cm/s、(16.82±1.67)cm/s、(19.47±2.03)cm/s,组间差异具有统计学意义(P<0.05)。观察组治疗后血清IL-1β(120.47±12.79)pg/ml、IL-6(0.24±0.03)pg/ml、ET-1(59.97±6.06)ng/L均低于对照组的(134.65±13.86)pg/ml、(0.35±0.07)pg/ml、(63.47±6.49)ng/L,组间具有统计学差异(P<0.05)。两组不良反应发生率分别为9.30%、4.65%,两组比较差异无统计学意义(P>0.05)。结论:和解汤与耳穴贴压联合治疗少阳郁热型颈性眩晕疗效满意,可有效改善患者椎基底动脉血流动力学,下调IL-1β、IL-6、ET-1水平,较好改善其眩晕症状,且安全性较好。     

Potential anti-inflammatory effect of dapagliflozin in HCHF diet- induced fatty liver degeneration through inhibition of TNF-α, IL-1β, and IL-18 in rat liver

Non-alcoholic fatty liver (NAFLD) is accompanied by an increased expression of oxidative stress parameters, in addition to the inflammatory cytokines; tumor necrosis factor alpha (TNF-α), interleukin type 1beta (IL-1β), and interleukin type 18 (IL-18). The aim of this study is to investigate the effect of dapagliflizon (DAPA) on high carbohydrate-high fat (HCHF) diet-induced expression of inflammatory cytokines in rat liver. NAFLD was induced by feeding the rats HCHF diet (consist of animal fat tallow and standard show pellets) and the consumption of fructose in drinking water (10%) for 12 or 18 weeks. The oral administration of DAPA (1 mg/kg/day) from 13th week to 18th week significantly improved NAFLD as indicated by a significant reduction in liver aminotransferases in addition to a significant decrease of serum MDA, cholesterol, triglyceride and LDL-cholesterol with concomitant significant elevation of HDL-cholesterol. DAPA-treated animals showed a significant reduction of liver homogenate content of TNF-α, IL-1β, and IL-18. These results indicate that the administration of DAPA may be beneficial against HCHF diet-induced NAFLD. Histopathological examination of liver specimens supported the conclusion that DAPA improves steatohepatitis induced by HCHF diet.     

HSP90β干扰和过表达慢病毒载体的构建及其在骨肉瘤细胞Saos-2中的表达

目的:获得热休克蛋白90β(HSP90β)基因干扰和过表达慢病毒表达系统，并检测其在人骨肉瘤细胞株Saos-2中的表达水平。方法:设计合成shRNA，以慢病毒表达质粒构建HSP90β干扰和过表达载体，酶切电泳、测序技术鉴定载体构建是否成功。重组病毒转染H1299细胞，以嘌呤霉素筛选稳定转染的Saos-2细胞，通过荧光显微镜观察计数获得转染效率。将感染好的细胞分为干扰NC组（NEG-shRNA）、干扰组（shRNA-HSP90β）、过表达NC对照组（NEG-pEZ）及过表达组（pEZ-HSP90β）。通过qRT-PCR 与Western blotting 分别从mRNA 和蛋白表达水平验证目的基因的干扰和过表达水平。结果:插入慢病毒表达载体的基因片段与目的基因的碱基序列完全一致。病毒包装成功后，嘌呤霉素最小致死浓度1 μg/ml，感染复数200，感染人Saos-2的感染效率达80%，其中shRNA-HSP90β组干扰效率为86.35%，pEZ-HSP90β组的mRNA相对表达量增加2.8倍。进一步研究发现，shRNA-HSP90β组较NEG-shRNA组中HSP90β蛋白表达明显降低，pEZ-HSP90β组较NEG-pEZ组HSP90β蛋白表达增加。结论:HSP90β基因干扰和过表达慢病毒载体构建成功，并能够在Saos-2中稳定表达。     

加味逍遥散联合三维适形放疗对原发性肝癌患者血清生长因子及免疫功能的影响

目的:观察加味逍遥散联合三维适形放疗对原发性肝癌(PLC)患者血清肝细胞生长因子(HGF)、转化生长因子-β1(TGF-β1)及免疫功能的影响。方法:选取90例PLC患者为研究对象,按照随机数字表法分为观察组和对照组,每组45例。对照组采用经肝动脉化疗栓塞术(TACE)联合三维适形放疗治疗,观察组在对照组基础上联合加味逍遥散治疗。对比2组中医证候疗效和实体瘤疗效,观察治疗前后血清HGF、TGF-β1及免疫功能指标的变化,记录不良反应发生情况。结果:观察组中医证候改善率97.78%,高于对照组的77.78%,差异有统计学意义(P<0.05)。观察组实体瘤疗效有效率略高于对照组,差异无统计学意义(P>0.05)。与治疗前比较,治疗后2组HGF水平均升高(P<0.05),TGF-β1水平均降低(P<0.05),观察组2项指标水平升高或降低幅度均大于对照组(P<0.05)。与治疗前比较,治疗后2组CD3^+、CD4^+、CD4^+/CD8^+、自然杀伤细胞(NK细胞)值均升高(P<0.05),观察组以上4项指标值均高于对照组(P<0.05)。2组治疗过程中均无严重不良反应发生。结论:加味逍遥散联合三维适形放疗治疗PLC可提高临床疗效,改善患者的免疫功能,调节机体血清相关因子。