Thymoquinone Augments Cisplatin-Induced Apoptosis on Esophageal Carcinoma Through Mitigating the Activation of JAK2/STAT3 Pathway.

BACKGROUND: Thymoquinone (TQ) is the major constituent of Nigella sativa seed and has shown biological activity in various human carcinomas. However, few studies have reported its effect on esophageal carcinoma (EC). AIMS: To explore the chemosensitive effect and mechanism of TQ in augmentation of cisplatin (DDP)-induced apoptosis of EC, both in vitro and in vivo. METHODS: The viability and apoptosis of esophageal carcinoma cells were detected by the Cell Counting Kit-8 assay, flow cytometry, and Hoechst 33258 staining. The expression levels of JAK2, p-JAK2, STAT3, p-STAT3, Bax, Bcl-2, Cyclin D1, Survivin, and caspase-3, 7, 9 were evaluated by western blot analysis. The histological changes were examined by TUNEL technique and immunohistochemical analysis. RESULTS: TQ enhanced the proapoptotic effect of DDP in human esophageal carcinoma cell line Eca-109, while blocking the activation of JAK2/STAT3 signaling pathway. The apoptosis of esophageal carcinoma cells was induced via blocking the activation of JAK2/STAT3 by using a molecular inhibitor (WP1066). Consistent with the in vivo and in vitro results, TQ increased cellular apoptosis and enriched the chemosensitivity of DDP. CONCLUSIONS: TQ along with DDP may regulate the progression of EC and has potential to be a chemotherapeutic agent in EC.

Identification of Two Additional Susceptibility Loci for Inflammatory Bowel Disease in a Chinese Population.

BACKGROUND/AIMS: To investigate the associations between the rs1250569 (zinc finger MIZ-type containing 1, ZMIZ1), rs1042522 (tumour protein p53, TP53), and rs10114470 (tumour necrosis factor-like cytokine 1A, TL1A) polymorphisms and the development of inflammatory bowel disease (IBD) in a Chinese (Han) population. We analysed the expression of genes that predispose patients to Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A total of 381 IBD patients and 517 healthy controls were recruited into our study. Polymorphisms at the three loci were genotyped using polymerase chain reaction-ligation detection reactions (PCR-LDR). Genotype-phenotype correlations were analysed. Blood and gut samples were obtained and analysed using quantitative real-time PCR (qRT-PCR), western blot analysis, and immunohistochemistry to investigate the mRNA and protein levels and in situ expression of genes found to predispose patients to IBD. Furthermore, the expression of susceptible genes was further verified using a mouse dextran sulphate sodium (DSS)-induced acute colitis model. RESULTS: No significant association was detected between rs1250569 and rs1042522 genotypes and CD or UC susceptibility. However, the frequency of allele A of rs1250569 was much higher in CD patients than that in healthy controls (55.03% vs. 48.48%, respectively; p = 0.044). The mutation rates at rs10114470 were dramatically lower at both the genotype and allele level in patients than those in healthy controls (p = 0.002 at both the genotype and allele level). Additionally, increased ZMIZ1 and TL1A levels were detected in intestinal samples obtained from both IBD patients and DSS-treated mice. CONCLUSION: rs1250569 (ZMIZ1) and rs10114470 (TL1A) are two novel loci that indicate susceptibility to IBD in Han-Chinese patients. Consistent with previous studies, TL1A expression levels were higher in Chinese Han IBD patients and DSS-treated mice. Most importantly, we found that ZMIZ1 expression was markedly higher in both IBD patients and mice with experimentally induced colitis, suggesting that ZMIZ1 plays important roles in the pathogenesis of IBD.

Effect of subconjunctival injection with conbercept as an adjuvant to filtration surgery for open angle glaucoma: a prospective randomized interventional 6-month follow-up study.

AIM: To compare the safety and efficacy of subconjunctival injection with conbercept and 5-fluorouracil (5-FU) for open angle glaucoma (OAG) patients after filtration surgery. METHODS: As a prospective randomized interventional trial, 36 eyes from 36 patients after OAG surgery were collected and divided randomly into conbercept and 5-FU groups. All patients were subconjunctivally injected with either conbercept (0.2 mL) or 5-FU (0.2 mL) on the 5th day post-operatively. The intraocular pressure (IOP), number of medications used, type of conjunctival bleb, and complications were recorded and analyzed pre-operatively and 1d, 1wk, 1, 3 and 6mo post-injection. RESULTS: There were significant differences in IOP between the conbercept and 5-FU groups 1mo (conbercept group: 12.17±1.04 mm Hg; 5-FU group: 13.50±2.33 mm Hg, t=2.214, P=0.037), 3mo (conbercept group: 13.00±1.88 mm Hg; 5-FU group: 14.50±2.28 mm Hg, t=2.153, P=0.039), and 6mo post-injection (conbercept group: 13.28±2.95 mm Hg; 5-FU group: 15.22±2.49 mm Hg, t=2.140, P=0.040); however, in the number of medications, a prominent difference was not shown between groups on post-injection 6mo (t=1.312, P=0.200). Moreover, there was mild vascularity observed in the conbecept group than the 5-FU group 1d (3a, 3b, 3c: t=8.497, 6.693, 4.515, P=0.000), 1wk (3a, 3b, 3c: t=3.431, 6.408, 3.984, P=0.002, 0.000, 0.000), and 1mo post-injection (3a, 3b, 3c: t=2.466, 2.466, 2.503, P=0.019, 0.019, 0.017). Simultaneously, differences from other indicators between the two groups were not demonstrated. Also, there was a lower probability of corneal epithelial stripping in the conbercept group than the 5-FU group (χ 2=4.500, P=0.034). CONCLUSION: Subconjunctival injection of conbercept has a safe, effective, and tolerable profile for open angle glaucoma patients with distinct conjunctival congestion after filtration surgery.

Report of a rare case and review of adult intestinal duplication at the opposite side of mesenteric margin.

CONTEXT: To study the previously discovered clinical entity of adult intestinal duplication and its treatment, and propose an extension to its existing classification. CASE REPORT: We report the case of an adult male with abdominal pain, constipation and vomiting. This patient underwent surgical separation of adhesions, reduction of torsion and intestinal decompression. Postoperative pathological findings confirmed the rare diagnosis of intestinal duplication. CONCLUSION: Adult intestinal duplication is quite rare. Its clinical manifestations are nonspecific. From this finding of intestinal duplication originating at the opposite side of the mesenteric margin, a further extension of the existing anatomical classification is proposed.

Survival rate variation with different histological subtypes of poor prognostic male anal squamous cell carcinoma: a population-based study.

BACKGROUND AND OBJECTIVE: The prognosis of male anal squamous cell carcinoma (MASCC) and female anal squamous cell carcinoma (FASCC) is variable. The influence of tumor subtype on the survival rate and gender is poorly known. Our study is the largest population-based study and aims to outline the difference in survival between MASCC and FASCC patients. METHODS: A retrospective population-based study was performed to compare the disease-specific mortalities (DSMs) between genders related to the tumor subtypes. The Surveillance, Epidemiology, and End Results (SEER) program database was employed to obtain the data from January 1988 to December 2014. RESULTS: A total of 4,516, (3,249 males and 1,267 females), patients with anal squamous cell carcinomas (ASCC) were investigated. The 5-year DSMs were 24.18% and 18.08% for men and women, respectively. The univariate analysis of the male basaloid squamous cell carcinoma (BSCC) and cloacogenic carcinoma (CC) patients demonstrated higher DSMs (P <0.001). Moreover, in the multivariate analysis, BSCC and CC were associated with soaring DSMs in male patients (P < 0.05). CONCLUSIONS: In the cohort of BSCC and CC patients, male patients demonstrated a considerable decrease in survival rate compared to females. A more precise classification of ASCC and individualized management for MASCC are warranted.

ROS and ROS-Mediated Cellular Signaling.

It has long been recognized that an increase of reactive oxygen species (ROS) can modify the cell-signaling proteins and have functional consequences, which successively mediate pathological processes such as atherosclerosis, diabetes, unchecked growth, neurodegeneration, inflammation, and aging. While numerous articles have demonstrated the impacts of ROS on various signaling pathways and clarify the mechanism of action of cell-signaling proteins, their influence on the level of intracellular ROS, and their complex interactions among multiple ROS associated signaling pathways, the systemic summary is necessary. In this review paper, we particularly focus on the pattern of the generation and homeostasis of intracellular ROS, the mechanisms and targets of ROS impacting on cell-signaling proteins (NF-κB, MAPKs, Keap1-Nrf2-ARE, and PI3K-Akt), ion channels and transporters (Ca(2+) and mPTP), and modifying protein kinase and Ubiquitination/Proteasome System.

Transcriptome Analysis and Comparison of Marmota monax and Marmota himalayana.

The Eastern woodchuck (Marmota monax) is a classical animal model for studying hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) in humans. Recently, we found that Marmota himalayana, an Asian animal species closely related to Marmota monax, is susceptible to woodchuck hepatitis virus (WHV) infection and can be used as a new mammalian model for HBV infection. However, the lack of genomic sequence information of both Marmota models strongly limited their application breadth and depth. To address this major obstacle of the Marmota models, we utilized Illumina RNA-Seq technology to sequence the cDNA libraries of liver and spleen samples of two Marmota monax and four Marmota himalayana. In total, over 13 billion nucleotide bases were sequenced and approximately 1.5 billion clean reads were obtained. Following assembly, 106,496 consensus sequences of Marmota monax and 78,483 consensus sequences of Marmota himalayana were detected. For functional annotation, in total 73,603 Unigenes of Marmota monax and 78,483 Unigenes of Marmota himalayana were identified using different databases (NR, NT, Swiss-Prot, KEGG, COG, GO). The Unigenes were aligned by blastx to protein databases to decide the coding DNA sequences (CDS) and in total 41,247 CDS of Marmota monax and 34,033 CDS of Marmota himalayana were predicted. The single nucleotide polymorphisms (SNPs) and the simple sequence repeats (SSRs) were also analyzed for all Unigenes obtained. Moreover, a large-scale transcriptome comparison was performed and revealed a high similarity in transcriptome sequences between the two marmota species. Our study provides an extensive amount of novel sequence information for Marmota monax and Marmota himalayana. This information may serve as a valuable genomics resource for further molecular, developmental and comparative evolutionary studies, as well as for the identification and characterization of functional genes that are involved in WHV infection and HCC development in the woodchuck model.

Report of a rare case and review of adult intestinal duplication at the opposite side of mesenteric margin

ABSTRACT CONTEXT: To study the previously discovered clinical entity of adult intestinal duplication and its treatment, and propose an extension to its existing classification. CASE REPORT: We report the case of an adult male with abdominal pain, constipation and vomiting. This patient underwent surgical separation of adhesions, reduction of torsion and intestinal decompression. Postoperative pathological findings confirmed the rare diagnosis of intestinal duplication. CONCLUSION: Adult intestinal duplication is quite rare. Its clinical manifestations are nonspecific. From this finding of intestinal duplication originating at the opposite side of the mesenteric margin, a further extension of the existing anatomical classification is proposed.