Value of tumor size as a prognostic factor in metastatic colorectal cancer patients after chemotherapy: a population-based study.

Aim: To evaluate the relationship between tumor size and survival in metastatic colorectal cancer (mCRC) patients who received chemotherapy. Materials & methods: SEER database was accessed for eligible patients. Multivariate Cox regression analysis was performed to compare the effect of tumor size on overall survival (OS) and CRC-specific survival (CCSS). Results: Tumor size ≥5 cm was an independent risk factor for OS and CCSS in mCRC patients treated with chemotherapy. Tumor size <5 cm did not show a survival advantage in patients whose primary tumor site was rectosigmoid junction, while tumor size ≥5 cm was associated with poor OS and CCSS in left-and right-sided colorectal cancer. Conclusion: Tumor size ≥5 cm was associated with poor prognosis after receiving chemotherapy treatment and a risk factor for survival of mCRC.

[Expression and characterization of mesophilic GH1 ß-glucosidase CdBglA from acidophilic Cuniculiplasma divulgatum].

ß-glucosidase has important applications in food, pharmaceutics, biomass conversion and other fields, exploring ß-glucosidase with strong adaptability and excellent properties thus has received extensive interest. In this study, a novel glucosidase from the GH1 family derived from Cuniculiplasma divulgatum was cloned, expressed, and characterized, aiming to find a better ß-glucosidase. The amino acid sequences of GH1 family glucosidase derived from C. divulgatum were obtained from the NCBI database, and a recombinant plasmid pET-30a(+)-CdBglA was constructed. The recombinant protein was induced to express in Escherichia coli BL21(DE3). The enzymatic properties of the purified CdBglA were studied. The molecular weight of the recombinant CdBglA was 56.0 kDa. The optimum pH and temperature were 5.5 and 55 ℃, respectively. The enzyme showed good pH stability, 92.33% of the initial activity could be retained when treated under pH 5.5-11.0 for 1 h. When pNPG was used as a substrate, the kinetic parameters Km, Vmax and Kcat/Km were 0.81 mmol, 291.99 µmol/(mg·min), and 387.50 s-1 mmol-1, respectively. 90.33% of the initial enzyme activity could be retained when CdBglA was placed with various heavy metal ions at a final concentration of 5 mmol/L. The enzyme activity was increased by 28.67% under 15% ethanol solution, remained unchanged under 20% ethanol, and 43.68% of the enzyme activity could still be retained under 30% ethanol. The enzyme has an obvious activation effect at 0-1.5 mol/L NaCl and can tolerate 0.8 mol/L glucose. In conclusion, CdBglA is an acidic and mesophilic enzyme with broad pH stability and strong tolerance to most metal ions, organic solvents, NaCl and glucose. These characteristics may facilitate future theoretical research and industrial production.

[Expression and characterization of a bifunctional thermal ß-glucosidase IuBgl3 from thermophilic archaeon Infirmifilum uzonense].

ß-glucosidase has important applications in food, medicine, biomass conversion and other fields. Therefore, exploring ß-glucosidase with strong stability and excellent properties is a research hotspot. In this study, a GH3 family ß-glucosidase gene named Iubgl3 was successfully cloned from Infirmifilum uzonense. Sequence analysis showed that the full length of Iubgl3 was 2 106 bp, encoding 702 amino acids, with a theoretical molecular weight of 77.0 kDa. The gene was cloned and expressed in E. coli and the enzymatic properties of purified IuBgl3 were studied. The results showed that the optimal pH and temperature for pNPG hydrolysis were 5.0 and 85 ℃, respectively. The enzyme has good thermal stability, and more than 85% of enzyme activity can be retained after being treated at 80 ℃ for2 h. This enzyme has good pH stability and more than 85% of its activity can be retained after being treated at pH 4.0-11.0 for 1 h. It was found that the enzyme had high hydrolysis ability to p-nitrophenyl ß-d-glucoside (pNPG) and p-nitrophenyl ß-d-xylopyranoside (pNPX). When pNPG was used as the substrate, the kinetic parameters Km and Vmax were 0.38 mmol and 248.55 µmol/(mg·min), respectively, and the catalytic efficiency kcat/Km was 6 149.20 s-1mmol-1. Most metal ions had no significant effect on the enzyme activity of IuBgl3. SDS completely inactivated the enzyme, while EDTA increased the enzyme activity by 30%. This study expanded the ß-glucosidase gene diversity of the thermophilic archaea GH3 family and obtained a thermostable acid bifunctional enzyme with good industrial application potential.

Biodegradation and Detoxification of Azo Dyes by Halophilic/Halotolerant Microflora Isolated From the Salt Fields of Tibet Autonomous Region China.

This study aimed to decolorize azo dyes in high-salt industrial wastewater under high-salt and low oxygen conditions using extreme halophilic/halotolerant bacteria screened from the salt fields of Tibet, which consisted of Enterococcus, unclassified Enterobacteriaceae, Staphylococcus, Bacillus, and Kosakonia. Under the optimal conditions, 600 mg/l Congo red, Direct Black G (DBG), Amaranth, methyl red, and methyl orange could be completely decolorized in 24, 8, 8, 12, and 12 h, respectively. When the DBG concentration was 600 mg/l, NADH-DCIP, laccase, and azo reductase were confirmed to be the primary reductase and oxidase during the degradation process, and the degradation pathways were verified. The microflora could not only tolerate changes in salt concentrations of 0-80 g/l, but also displayed strong degradative ability. Under high-salt concentrations (≥ 60 g/l NaCl), NADH-DCIP reductase was primarily used to decolorize the azo dye. However, under low salt concentrations (≤ 40 g/l NaCl), azo reductase began to function, and manganese peroxidase and lignin peroxidase could cooperate to participate in DBG degradation. Additionally, the halophilic/halophilic microflora was shown to convert the toxic DBG dye to metabolites of low toxicity based on phytotoxicity analysis, and a new mechanism for the microflora to degrade DBG was proposed based on intermediates identified by liquid chromatography-mass spectrometry (LC-MS). This study revealed that the halophilic/halophilic microflora has effective ecological and industrial value for treating wastewater from the textile industry.

Regulation of Nir gene in Lactobacillus plantarum WU14 mediated by GlnR.

Nitrogen (N) is an essential element in the biosynthesis of key cellular components, such as proteins and nucleic acids, in all living organisms. Nitrite, as a form of nitrogen utilization, is the main nutrient for microbial growth. However, nitrite is a potential carcinogen that combines with secondary amines, which are breakdown products of proteins, to produce N-nitroso compounds that are strongly carcinogenic. Nitrite reductase (Nir) produced by microorganisms can reduce nitrite. Binding of GlnR to the promoter of nitrogen metabolism gene can regulate the expression of Nir operon. In this study, nitrite-resistant Lactobacillus plantarum WU14 was isolated from Pickles and its protease Nir was analyzed. GlnR-mediated regulation of L. plantarum WU14 Nir gene was investigated in this study. New GlnR and Nir genes were obtained from L. plantarum WU14. The regulation effect of GlnR on Nir gene was examined by gel block test, yeast two-hybrid system, bacterial single hybrid system and qRT-RCR. Detailed analysis showed that GlnR ound to the Nir promoter region and interacted with Nir at low nitrite concentrations, positively regulating the expression of NIR. However, the transcription levels of GlnR and Nir decreased gradually with increasing nitrite concentration. The results of this study improve our understanding of the function of the Nir operon regulatory system and serve as the ground for further study of the signal transduction pathway in lactic acid bacteria.

The Efficacy and Safety of Acupuncture for Prophylaxis of Vestibular Migraine: A Study Protocol for a Randomized Controlled Trial.

Introduction: With a high incidence rate and low diagnosis rate, vestibular migraine (VM) can seriously affect the quality of life of patients, but it remains difficult to manage by current treatment options. Acupuncture may be a potential treatment option for VM prophylaxis, but the currently available evidence is still uncertain. Therefore, this trial aims to evaluate the efficacy and safety of acupuncture for VM prophylaxis. Methods: This is a 28-week parallel, randomized, controlled clinical trial including 4 weeks of baseline, 8 weeks of treatment, and 16 weeks of follow-up. A total of 72 participants will be randomly assigned to two groups. The participants will receive acupuncture in the experimental group, while the participants in the control group will be treated with venlafaxine. The primary outcome measures are change in vertigo/migraine days and vertigo/migraine attacks, vertigo severity, and migraine intensity per 4 weeks from baseline. The secondary outcome measures are change in doses of rescue medication, anxiety level, depression level, and quality of life per 4 weeks from baseline. Adverse events will be recorded for safety evaluation. Discussion: This study will investigate the efficacy and safety of acupuncture for VM prophylaxis. The results will contribute to determining whether acupuncture can serve as an optional treatment strategy for treating VM. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT0464088.

Is acupuncture effective and safe for prophylaxis of vestibular migraine?: A protocol for systematic review and meta analysis.

BACKGROUND: Increasing studies indicate that acupuncture can be used for treating vestibular migraine (VM), but current evidence remains inconclusive. Thus, this protocol aims to evaluate the evidence regarding the efficacy and safety of acupuncture for VM prophylaxis by conducting a systematic review and meta-analysis. METHODS: Studies will be retrieved by searching electronic databases from their inception to December 2020, including EMBASE, PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), and Chinese Science and Technology Periodical Database (VIP). Eligible randomized controlled trials involving acupuncture for VM prophylaxis will be included. Study screening, data collection, and assessment for risk of bias will be executed by 2 independent reviewers. Meta-analyses will be conducted, followed by subgroup analysis if significant heterogeneity is detected. Sensitivity analysis and summary of the strength of the evidence will also be performed. RESULTS: The results of the present systematic review and meta-analysis will verify the efficacy and safety of acupuncture for VM prophylaxis. CONCLUSION: This review will determine the efficacy and safety of acupuncture on VM prophylaxis. The findings are expected to verified whether acupuncture can be an alternative treatment for VM prophylaxis. ETHICS AND DISSEMINATION: Given that a systematic review and meta-analysis will not involve private information of individuals, ethical approval is not required. Relevant results and findings will be submitted to an academic journal for peer reviews. PROSPERO REGISTRATION NUMBER: CRD42020202588.

CXCR4 and CXCR3 are two distinct prognostic biomarkers in breast cancer: Database mining for CXCR family members.

CXC chemokine receptors (CXCRs) and chemokines are involved in tissue development and homeostasis, including in cancer development and progression. To date, seven CXCRs have been identified. However, the expression of CXCRs and their influence on the occurrence and development of breast cancer (BC) requires further investigation. In the present study, mRNA expression levels of the seven CXCRs were compared between normal tissues and several cancer types using the Oncomine database. Highly expressed CXCRs were selected and the expression levels of these CXCRs were examined in different subtypes of BC using the Gene Expression­Based Outcome for Breast Cancer database. Finally, the prognostic value of these CXCRs was examined using Kaplan­Meier plotter. It was found that, compared with normal controls, transcripts of CXCR4 and CXCR3 were significantly overexpressed in BC samples compared with other CXCRs. Survival analysis showed that high expression of CXCR4 promoted the recurrence of BC but had no impact on overall survival (OS), while a high level of CXCR3 transcript expression was significantly associated with increased survival in patients with BC. With regards to different subtypes of BC, the present study revealed that high CXCR4 transcript expression was significantly associated with both longer relapse­free survival and OS only in basal­like BC. Furthermore, CXCR4 promoted chemosensitivity in patients with basal­like BC and induced resistance against endocrine therapy for patients with luminal A BC. Thus, CXCR4 and CXCR3 are two distinct prognostic biomarkers and further studies are required.

Jiedu Sangen Decoction Inhibits the Invasion and Metastasis of Colorectal Cancer Cells by Regulating EMT through the Hippo Signaling Pathway.

Colorectal cancer (CRC) is one of the most common malignant tumors affecting the digestive tract. Moreover, the invasion and metastasis of CRC are the main reason therapy is usually inefficient. Decreased intercellular adhesion and enhanced cell motility induced by epithelial-mesenchymal transition (EMT) provide the basic conditions for the invasion and metastasis of the epithelial tumor cells of CRC. The Jiedu Sangen Decoction (JSD) is a prescription that has been used for more than 50 years in the treatment of CRC in the Zhejiang Hospital of Traditional Chinese Medicine. The aim of this study was to investigate the mechanism of JSD-triggered inhibition of invasion and metastasis in colon cancer. In vitro, the EMT model of the SW480 cells was induced by using epithelial growth factor (50 ng/mL). In vivo, the murine model of liver metastasis was constructed by inoculating mice with the SW480 cells. The effects of JSD on cell migration, invasion, and proliferation were determined using the transwell assay and CCK-8 assay. Moreover, the proteins related to the EMT process and the Hippo signaling pathway in the cancerous tissues and cell lines were determined by western blotting and immunostaining. JSD could significantly inhibit the proliferation, migration, and invasion of CRC cells and reverse their EMT status (all, P < 0.05). Moreover, after intervention with JSD, the levels of E-Cadherin (E-cad) increased, whereas the expression levels of N-Cadherin (N-cad), Yes-associated protein (YAP), and the transcriptional coactivator with the PDZ-binding motif (TAZ) decreased in both the SW480 cells and the tumor tissues. In summary, JSD reversed EMT and inhibited the invasion and metastasis of CRC cells through the Hippo signaling pathway.

Association between the overexpression of Her3 and clinical pathology and prognosis of colorectal cancer: A meta-analysis.

BACKGROUND: This study aimed to investigate the association between the overexpression of human epidermal growth factor receptor-3 (Her3) and the clinicopathological parameters and survival of patients with colorectal cancer (CRC). METHODS: Relevant studies on the overexpression of Her3 (measured by immunohistochemistry) and overall survival (OS) in patients with CRC were searched for in PubMed, EMBASE, and Cochrane Library. Published data were extracted and computed into odds ratios (ORs) for assessing the association of Her3 overexpression with tumor differentiation, tumor node metastasis (TNM) stage, position of colon cancer, sex, and age. Prognostic data were computed into hazard ratios (HRs) for OS. RESULTS: Eight studies including 1716 patients with CRC were included in this meta-analysis. The results revealed a significant association between Her3 overexpression and tumor differentiation [OR = 2.38; 95% confidence interval (95% CI): 1.76-3.22; P < .001], TNM tumor stage (OR = 0.71; 95% CI: 0.53-0.96; P = .03), and position of colon cancer (OR = 1.71; 95% CI: 1.28-2.27; P < .001). While patients with Her3 overexpression demonstrated a worse tumor response (OR = 0.31; 95% CI: 0.16-0.60; P < .001) and OS after treatment with cetuximab (HR = 1.86; 95% CI: 1.24-2.79; P = .003), they demonstrated better OS after symptomatic treatment (HR = 0.65; 95% CI: 0.50-0.85; P = .002). Her3 overexpression was not associated with sex (OR = 1.03; 95% CI: 0.83-1.28; P = .79), age (OR = 0.96; 95% CI: 0.75-1.24; P = .77), colon or rectum site (OR = 0.79; 95% CI: 0.44-1.43; P = .44), and total OS (HR = 1.09; 95% CI: 0.69-1.72; P = .72). CONCLUSION: Her3 expression is associated with the clinical pathology and prognosis of CRC, which explains the nonefficacy of cetuximab treatment in patients with CRC.