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The pro-inflammatory cytokines secreted by Müller cells aggregate retinal cell loss and vascularization in diabetic retinopathy (DR). The deubiquitinase BRCA1–BRCA2-containing complex subunit 3 (BRCC3)-mediated nucleotide-binding domain and leucine-rich repeat receptor containing a pyrin domain 3 (NLRP3) inflammasome activation participate in this progress. This study aims to clarify whether the E3 ubiquitin ligase synoviolin (SYVN1) relieves DR via regulating the BRCC3/NLRP3 axis. The DR model was established using streptozotocin-induced mice. Immunofluorescence staining with anti-CD31, anti-glutamine synthetase, and anti-vimentin was performed to identify DR and Müller cells. Levels of pro-inflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, IL-6, and IL-18, in murine serum and Müller cell supernatants were determined. Co-immunoprecipitation (Co-IP) and ubiquitination assays were used to clarify the interactions among SYVN1, BRCC3, and NLRP3. SYVN1 was reduced and BRCC3 was increased in DR retina and high glucose (HG)-induced Müller cells. Overexpressing 1 promoted the ubiquitination and degradation of BRCC3 and reduced the secretion of proinflammatory cytokines in HG-induced Müller cells. The simultaneous overexpression of 1 and Brcc3 restored the reduction of pro-inflammatory cytokines caused by the overexpression of 1 alone. Co-IP experiments confirmed the interaction between BRCC3 and NLRP3. SYVN1-mediated BRCC3 downregulation promoted NLRP3 ubiquitination and reduced pro-inflammatory cytokine secretion. 1 overexpression reduced retinal vascularization and inflammatory cytokine secretion in DR mice. SYVN1 has a protective effect on DR, whose molecular mechanisms are partly through SYVN1-mediated ubiquitination of BRCC3 and the subsequent downregulation of NLRP3.

Objective. To systematically review whether the Kangai injection (KAI), which is commonly used traditional Chinese medicine, can improve the clinical efficacy of chemotherapy and relieve adverse reactions of chemotherapy in advanced colorectal cancer (CRC) patients. Methods. A comprehensive literature search was performed in three English and three Chinese electronic databases until March 2019. The literature was screened by EndNote X8 and data were analysed by RevMan5 and Stata12.0. Results. This meta-analysis consisted of twenty-eight studies, of which 2310 cases were reported. Among the 2310 cases, 1207 cases were treated with KAI combined with chemotherapy and 1103 cases were treated with chemotherapy alone. The results showed that KAI combined with chemotherapy significantly improved tumor response (Risk Ratio (RR) =1.32; 95% confidence interval (CI): 1.22-1.43; p p p p p p p p = 0.0004); increased immune function (CD3+: MD=6.34; 95% CI: 5.52-7.16; p < 0.00001, CD4+: MD=-5.99; 95% CI: 5.20-6.78; p < 0.00001; and CD4+/CD8+: MD=0.34; 95% CI: 0.14-0.54; p < 0.0009), and prolonged survival time (OR =1.77; 95% CI: 1.25-2.50; p = 0.001). Renal dysfunction caused by chemotherapy was not affected by KAI treatment (Odds Ratio (OR) =0.53; 95%IC: 0.25-1.12; p = 0.10). Conclusion. KAI can increase clinical effectiveness, improve quality of life, alleviate ADRs, and prolong survival time in advanced colorectal (CRC) patients receiving chemotherapy.

Objective. To systematically evaluate the efficacy of Xihuang pill (XHP) in breast cancer patients receiving chemotherapy. Methods. Three English and four Chinese databases were searched. Literature was screened using EndNote X7 and data were analyzed by Review Manager. Results. This review included 13 randomized clinical studies of 1272 patients. The results showed that XHP increased the tumor response [risk ratio (RR) = 2.91; 95% confidence interval (CI): 1.98-4.26] and improved Karnofsky performance score (KPS) for breast cancer patients receiving chemotherapy [RR = 4.96; 95% CI = 2.07-11.86]. In addition, XHP treatment significantly reduced chemotherapy-induced adverse events, including nausea and vomiting [RR = 0.50; 95% CI = 0.33-0.74], WBC reduction [RR = 0.71; 95% CI = 0.47-1.06], platelet reduction [RR = 0.53; 95% CI = 0.19-1.44], hemoglobin reduction [RR = 0.31; 95% CI = 0.19-0.52], and hepatic function damage [RR = 0.63; 95% CI = 0.35-1.11]. Conclusion. XHP combined with chemotherapy in comparison with chemotherapy alone could significantly enhance the tumor response, improve KPS, and alleviate toxicity induced by chemotherapy in breast cancer patients.

Tumor immune cell infiltration (ICI) has been reported in various studies to be correlated with tumor diagnosis, clinical treatment sensitivity and prognosis. It is an important direction to study the characteristics of immune cell infiltration and develop new prognostic markers to improve the treatment of colon cancer. In this paper, we systematically analyzed the ICI characteristics and obtained three ICI clusters. Then, the ICI scores were constructed and its prognostic implications were discussed. From the results, the ICI score patterns were linked to a great survival difference (p

Colorectal cancer (CRC) is a commonly occurring tumour with poor prognosis. Autophagy-related long non-coding RNAs (lncRNAs) have received much attention as biomarkers for cancer prognosis and diagnosis. However, few studies have focused on their prognostic predictive value specifically in CRC. This research aimed to construct a robust autophagy-related lncRNA prognostic signature for CRC. Autophagy-related lncRNAs from The Cancer Genome Atlas database were screened using univariate Cox, LASSO, and multivariate Cox regression analyses, and the resulting key lncRNAs were used to establish a prognostic risk score model. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression of several lncRNAs in cancer tissues from CRC patients and in normal tissues adjacent to the cancer tissues. A prognostic signature comprising lncRNAs AC125603.2, LINC00909, AC016876.1, MIR210HG, AC009237.14, and LINC01063 was identified in patients with CRC. A graphical nomogram based on the autophagy-related lncRNA signature was developed to predict CRC patients' 1-, 3-, and 5-year survival. Overall survival in patients with low risk scores was significantly better than in those with high risk scores (P < 0.0001); a similar result was obtained in an internal validation sample. The nomogram was shown to be suitable for clinical use and gave correct predictions. The 1- and 3-year values of the area under the receiver operating characteristic curve were 0.797 and 0.771 in the model sample, and 0.656 and 0.642 in the internal validation sample, respectively. The C-index values for the verification samples and training samples were 0.756 (95% CI = 0.668-0.762) and 0.715 (95% CI = 0.683-0.829), respectively. Gene set enrichment analysis showed that the six autophagy-related lncRNAs were greatly enriched in CRC-related signalling pathways, including p53 and VEGF signalling. The qRT-PCR results showed that the expression of lncRNAs in CRC was higher than that in adjacent tissues, consistent with the expression trends of lncRNAs in the CRC data set. In summary, we established a signature of six autophagy-related lncRNAs that could effectively guide clinical prediction of prognosis in patients with CRC. This lncRNA signature has significant clinical implications for improving the prediction of outcomes and, with further prospective validation, could be used to guide tailored therapy for CRC patients.

BACKGROUND: Endophyte has now become a potential source for the discovery of novel natural products, as they participate in biochemical pathways of their hosts and produce analogous or novel bioactive compounds. As an epiphytic plant, Dendrobium officinale is one of precious Chinese medicines with various activities. It is well known for containing diverse endophytes, but so far not much is known about their secondary metabolites. METHODS: the plant tissues were cut and cultured on agar plates to isolate and purify the endophytic bacteria from Dendrobium officinale. Taxonomical identification of strains was performed by 16s rRNA. At the same time, the crude extracts of the strains were tested for antibacterial and cytotoxic activities to screen out one endophyte, Streptomyces sp. SH-1.2-R-15 for further study. After scale-up fermentation, isolation, purification and structure elucidation by using MS, 1D/2D-NMR spectroscopic method, secondary metabolites were identified and submitted for biological activity test. RESULTS: Fifty-eight endophytic strains representing 9 genera were obtained, with 50% of strains were Streptomyces. One of the most active strain, Streptomyces sp. 1.2-R-15, was selected for bioassay-guided isolation, which led to the discovery of two new peptide-type compounds 1 and 2, as well as a bioactive chartreusin, and four other known natural products. Their structures were determined by comprehensive spectroscopic techniques. Chartreusin showed potent cytotoxicity against Hep3B2.1-7 (IC(50) =18.19 µM) and H1299 (IC(50) =19.74 µM) cancer cell lines, and antibacterial activity against S. aureus (IC(50) =23.25 µM). CONCLUSIONS: This study highlights the endophytic bacteria from medical plant D. officinale have potential bioactivity and natural product diversity, thus implicates them as a valuable source for new anticancer and antibiotics agents.

Background Traditional Chinese medicine (TCM) formulations have proven to be advantageous in clinical treatment and prevention of disease. LiuWei DiHuang Pill (LWDH Pill) is a TCM that was employed to treat type 2 diabetes mellitus (T2DM). However, a holistic network pharmacology approach to understanding the active ingredients and the therapeutic mechanisms underlying T2DM has not been pursued. Methods A network pharmacology approach including drug-likeness evaluation, oral bioavailability prediction, virtual docking, and network analysis has been used to predict the active ingredients and potential targets of LWDH Pill in the treatment of type 2 diabetes. Results The comprehensive network pharmacology approach was successfully to identify 45 active ingredients in LWDH Pill. 45 active ingredients hit by 163 potential targets related to T2DM. Ten of the more highly predictive components (such as :quercetin, Kaempferol, Stigmasterol, beta-sitosterol, Kadsurenone, Diosgenin, hancinone C, Hederagenin, Garcinone B, Isofucosterol) are involved in anti-inflammatory, anti-oxidative stress, and the reduction of beta cell damage. LWDH Pill may play a role in the treatment of T2DM and its complications (atherosclerosis and nephropathy) through the AGE-RAGE signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. Conclusion Based on a systematic network pharmacology approach, our works successfully predict the active ingredients and potential targets of LWDH Pill for application to T2DM and helps to illustrate mechanism of action on a comprehensive level. This study provides identify key genes and pathway associated with the prognosis and pathogenesis of T2DM from new insights, which also demonstrates a feasible method for the research of chemical basis and pharmacology in LWDH Pill.

Ethnopharmacological relevance Traditional Chinese medicine has been utilized for the treatment of cancer. Jianpi Jiedu decoction (JPJD), a traditional Chinese medicine formula, has been used for the treatment of colorectal cancer for decades. However, the underlying molecular mechanistic basis for the effect of JPJD on colorectal cancer is poorly understood. Aim of the study The aim of this study was to identify the effects of JPJD on human colon cancer cells in vitro as well as in vivo and to investigate the mechanistic basis for the anticancer effect of JPJD. Materials and methods The in vitro antitumor activity of JPJD was assessed by MTT assay, flow cytometric analysis, wound-healing assay, transwell assays, and tube formation assays in order to assess cell activity, apoptosis, migration, invasion, and angiogenesis, respectively. The anticancer properties of JPJD in vivo were assessed by immunohistochemistry in a nude mouse xenograft model of HCT116 cells. In addition, the level of mTOR/HIF-1α/VEGF signaling pathway proteins in HCT116 cells and tumor tissue was evaluated by immunoblotting. Results In vitro, JPJD significantly inhibited colorectal cancer cell lines viability and proliferation. Flow cytometry analysis demonstrated JPJD to induce HCT116 cell apoptosis. Additionally, JPJD effectively suppressed tumor cell migration, invasion, and angiogenesis by inhibiting the mTOR/HIF-1α/VEGF signaling pathway. In vivo, JPJD significantly inhibited HCT116 tumor growth in athymic nude mice, decreased the levels of CD34 as well as VEGF, and downregulated the mTOR/HIF-1α/VEGF pathway. Conclusions JPJD treatment produced anti-colorectal tumor effects by inhibiting tumorigenesis, metastasis, as well as angiogenesis through the mTOR/HIF-1α/VEGF pathway. Thus, these results provide a strong rationale for the therapeutic use of JPJD in cancer treatment. Further studies are required to investigate the mechanisms underlying anti-CRC effect of JPJD.

Objective. To systematically review the effect of invigorating Pi and detoxification (Jianpi Jiedu, (JPJD)) herbs in advanced colorectal cancer (CRC) patients receiving chemotherapy. Methods. Three English and four Chinese databases were searched. Literature was screened by EndNote X7 and data were analyzed by RevMan 5.2. Results. This review comprised 12 randomized clinical studies of 701 patients. The results showed that JPJD herbs improved the therapeutic effect on Chinese medicine symptoms [risk ratio (RR) = 1.59; 95% confidence interval (CI): 1.35~1.88] and Karnofsky performance score [RR = 2.07; 95% CI: 1.52~2.82] for advanced CRC patients receiving chemotherapy, lowered the Chinese medicine symptoms’ score [weighted mean difference = −2.44; 95% CI: −3.23~−1.64], reduced the incidence of nausea and vomiting [RR = 0.23; 95% CI: 0.11~0.49], improved platelet at toxicity grades III-IV [odds ratio = 0.29; 95% CI: 0.12~0.74] and I–IV [RR = 0.65; 95% CI: 0.51~0.82], and improved white blood cell at toxicity grades III-IV [RR = 0.37; 95% CI: 0.23~0.58] and I–IV [RR = 0.69; 95% CI: 0.60~0.79]. However, the results showed no significant effect on tumor response. Conclusion. JPJD herbs can improve quality of life, relieve symptoms, and reduce adverse events of advanced CRC patients receiving chemotherapy.

Several studies have previously reported that endothelial cells contributed to pathological fibrosis in proliferative diabetic retinopathy (PDR) through endothelial-mesenchymal transition (EndMT); however, the precise mechanism of this interaction has not been completely elucidated. The present study investigated the expression of microRNA (miR)-29a/b cluster in human retinal microvascular endothelial cells (HRMECs) and examined its functional role in high glucose (HG)-induced EndMT. HRMECs were exposed to glucose at concentrations of 5, 15, 30 and 50 mM for 7 days and reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence were conducted to determine the expression of genes associated with miR-29a/b and EndMT. A luciferase reporter gene assay was also performed to confirm the association between miR-29a/b and neurogenic locus notch homolog protein 2 (Notch2). The expression levels of miR-29a/b, and endothelial markers vascular endothelial cadherin and cluster of differentiation 31 were decreased, whereas the expression levels of Notch2 and mesenchymal markers, including α-smooth muscle actin, fibroblast-specific protein 1 (also named S100 calcium binding protein A4, S100A4), fibronectin and SNAI1 were increased in HRMECs under HG (30 nM) conditions. In addition, Notch2 was identified as a target of miR-29a and miR-29b. Overexpression of miR-29a/b downregulated the expression of Notch2 and subsequently suppressed HG-induced EndMT. Taken together, the results of the present study revealed that the miR-29/Notch2 signaling pathway may participate in the regulation of HG-induced EndMT, and may serve as a potential molecular target during fibrosis in PDR.

BACKGROUND Zuojinwan (ZJW) is a traditional Chinese prescription normally used for gastritis. Several studies indicated that it could fight against gastric cancer. This study was designed to determine the potential pharmacological mechanism of ZJW in the treatment of gastric cancer. MATERIAL AND METHODS Bioactive compounds and potential targets of ZJW and related genes of gastric cancer were retrieved from public databases. Pharmacological mechanisms including crucial ingredients, potential targets, and signaling pathways were determined using protein-protein interaction (PPI) and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Virtual docking was performed to validate the findings. RESULTS Network analysis identified 47 active ZJW compounds, and 48 potential ZJW target genes linked to gastric cancer. Quercetin, beta-sitosterol, isorhamnetin, wogonin, and baicalein were identified as potential candidate agents. Our PPI analysis results combined with previously published results indicated that matrix metalloproteinases family members MMP9, MMP1, and MMP3 may play key roles in the anti-gastric cancer effect of ZJW. Molecular docking analysis showed that these crucial targets had good affinity for the representative components in ZJW. GO and KEGG enrichment analysis showed that ZJW target genes functioned in multiple pathways for treating gastric cancer, including interleukin-17 signaling and platinum drug resistance. CONCLUSIONS Our results illuminate the active ingredients, associated targets, biological processes, and signaling pathways of ZJW in the treatment of gastric cancer. This study enhances our understanding of the potential effects of ZJW in gastric cancer and demonstrates a feasible method for discovering potential drugs from Chinese medicinal formulas.

PURPOSE: To assess psychometric properties of the Hong Kong Quality of Life Questionnaire (HKQ) using Rasch analysis and use it to assess cataract surgery outcomes. METHODS: The HKQ was interviewer administered to participants at baseline (preoperative) and 12 months of follow-up (postoperative). Rasch analysis was used to assess and improve psychometric properties of the HKQ using the preoperative data. The responsiveness of the HKQ was assessed on the stacked preoperative and postoperative data, reported with the effect size. RESULTS: One hundred ninety-nine participants (median age: 72 years; interquartile range: 65 to 78 years) with cataract completed the HKQ at the preoperative assessment. There were more women (58%) and most of the participants had bilateral cataract (83.9%). Nearly half of the participants had undergone surgery in one eye (45.2%) followed by bilateral surgery (38.7%). Psychometric assessment guided by Rasch analysis resulted into a 15-item HKQ with promising psychometric properties including adequate measurement precision (2.09), no misfitting items, near perfect targeting (−0.05), unidimensionality, and with no evidence of item bias. For those who completed the HKQ (n = 82, 41.2%) at the 12-month follow-up visit, all groups demonstrated statistically significant gains in the HKQ scores, with the highest gain in participants who had undergone bilateral surgery (effect size: 2.61). CONCLUSIONS: The 15-item HKQ was valid and psychometrically sound and might be a highly responsive instrument to measure cataract surgery outcomes in China. This study demonstrated that cataract surgery significantly improves quality of life in the Chinese population. [ J Refract Surg. 2018;34(6):413–418.]

Purpose: to assess cataract surgery outcome using the Rasch scaled Chinese version of the Catquest short-form. Methods: the Chinese translated and culturally adapted version of the Catquest-9SF was interviewer-administered to patients, pre and post cataract surgery. Rasch analysis was performed on the baseline data to revise the Catquest. For the surgical outcome assessment, we stacked pre- and post-surgical Catquest data to demonstrate improvement in visual function scores and responsiveness of the instrument to cataract surgery. Results: a total of 247 cataract patients (median age, 70 yrs; male 51.0%) completed the Catquest 9SF at baseline.The Catquest-9SF possessed adequate measurement precision of 2.15. No disordering of response categories were observed and all the items perfectly fit to the Rasch model except item 7 (outfit >1.5). A slight reduction in precision was observed after removing misfitting item 7 (Catquest-8SF-CN), but the precision value was well above the acceptable value of 2.00. Notably, the instrument was well targeted (mean person location 0.30), demonstrated no evidence of multidimensionality and DIF. At 12 months post-surgery, 74 (30%) patients came for follow-up and completed the Catquest. There was a significant improvement in the Catquest scores post cataract surgery with a considerably large effect size. Conclusion: the Catquest-8SF-CN demonstrated promising Rasch based psychometric properties and was highly responsive to cataract surgery. Refereed/Peer-reviewed

// Salman B. Hosain 1 , Sachin K. Khiste 1 , Mohammad B. Uddin 1 , Vindya Vorubindi 1 , Catherine Ingram 1 , Sifang Zhang 2 , Ronald A. Hill 1 , Xin Gu 3 , Yong-Yu Liu 1 1 Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe, Monroe, LA 71201, USA 2 Department of Integrated Chinese and Western Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China 3 Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA Correspondence to: Yong-Yu Liu, email: yliu@ulm.edu Keywords: tumor suppressor p53, epithelial-mesenchymal transition, cancer stem cells, glucosylceramide synthase, missense mutation Received: December 10, 2015 Accepted: July 26, 2016 Published: August 10, 2016 ABSTRACT Missense mutation of tumor suppressor p53, which exhibits oncogenic gain-of-function (GOF), not only promotes tumor progression, but also diminishes therapeutic efficacies of cancer treatments. However, it remains unclear how a p53 missense mutant contributes to induced pluripotency of cancer stem cells (CSCs) in tumors exposed to chemotherapeutic agents. More importantly, it may be possible to abrogate the GOF by restoring wild-type p53 activity, thereby overcoming the deleterious effects resulting from heterotetramer formation, which often compromises the efficacies of current approaches being used to reactivate p53 function. Herewith, we report that p53 R273H missense mutant urges cancer cells to spawn CSCs. SW48/TP53 cells, which heterozygously carry the p53 R273H hot-spot mutant (R273H/ + , introduced by a CRISPR/Casp9 system), were subchronically exposed to doxorubicin in cell culture and in tumor-bearing mice. We found that p53-R273H (TP53-Dox) cells were drug-resistant and exhibited epithelial-mesenchymal transition (EMT) and increased numbers of CSCs (CD44v6 + /CD133 + ), which resulted in enhanced wound healing and tumor formation. Inhibition of glucosylceramide synthase with d-threo -1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) sensitized p53-R273H cancer cells and tumor xenografts to doxorubicin treatments. Intriguingly, PDMP treatments restored wild-type p53 expression in heterozygous R273H mutant cells and in tumors, decreasing CSCs and sensitizing cells and tumors to treatments. This study demonstrated that p53-R273H promotes EMT and induced pluripotency of CSCs in cancer cells exposed to doxorubicin, mainly through Zeb1 and β-catenin transcription factors. Our results further indicate that restoration of p53 through inhibition of ceramide glycosylation might be an effective treatment approach for targeting cancers heterozygously harboring TP53 missense mutations.

Purpose: To translate, culturally adapt, and validate the original and previously validated shorter versions of the Visual Function Index (VF-14) questionnaire in a Chinese population. Methods: The VF-14 was completed by patients with cataract. The analysis was carried out in three phases: phase I, testing whether the VF-14 and its valid shorter versions,VF-8R and VF-11R, form valid scales in Chinese settings using Rasch analysis; phase II, developing completely new Chinese versions of the VF-14; phase III, testing whether the previously validated shorter versions of the VF-14 could be applied in a Chinese population. This was tested by assessing the agreement between the new Chinese (developed in phase II) and the previously validated shorter versions of the VF-14 using Bland-Altman plots. Results: A total of 456 patients (median age, 70 years; range, 40–92 years; females, 58%) completed the Chinese translated version of the VF-14. The VF-14 and the VF-11R demonstrated good Rasch based psychometric properties when a grossly misfitting item was removed. The VF-8R formed a valid scale without any modification. The scores of the VF-11R and the Chinese shorter version (VF-11RChin) showed very good agreement, with a mean difference of −0.18 logits and 95% limits of agreement between 0.11 and −0.47. Conclusions: The Chinese translated VF-14, VF-11R, and VF-8R were valid and could be applied to assess cataract outcomes in Chinese settings. The existing shorter version had good agreement with the new Chinese version, which signifies that there was no need to develop a different version of the VF-14 in China. Refereed/Peer-reviewed

In the title compound, C16H13NO2S, the C—SO2—NH—C torsion angle is −70.1 (2)°. The dihedral angle between the planes of the naphthyl ring system and the phenyl ring is 34.67 (4)°. In the crystal, molecules are linked by intermolecular N—H...O hydrogen bonds into chains along [100]. There are also π–π interactions between adjacent naphthyl groups [interplanar spacing = 3.541 (3) Å] for molecules stacked along [100].