Gastric cancer (GC) is among the most common malignant tumors worldwide. The inhibition of p53 ubiquitination can inhibit the progression of GC. The mechanism through which plasmolipin (PLLP) regulates p53 ubiquitination in GC remains unclear. In this study, the correlation between PLLP expression and the prognosis of GC was analyzed on the basis of data from The Cancer Genome Atlas database, and the expression characteristics of PLLP and p53 were verified by immunohistochemistry. A PLLP overexpression/knockdown GC cell model was constructed, and cell proliferation, apoptosis, and invasion were detected by Cell Counting Kit-8, flow cytometry, and Transwell assays. Coimmunoprecipitation and Western blotting were used to analyze the PLLP-tripartite motif-containing 59 (TRIM59)-p53 regulatory axis. The antitumor effect of PLLP in vivo was verified by tumor formation experiments in nude mice. Cycloheximide tracking assays, coimmunoprecipitation, and ubiquitination analysis were used to determine the effect of PLLP on p53 stability. Combined with bioinformatics prediction and experimental verification, the interaction between PLLP and the E3 ubiquitin ligase TRIM59 and its regulatory effect on the ubiquitination and degradation of p53 were analyzed. Flow cytometry and Transwell assays were used to verify the biological effect of the PLLP-TRIM59-p53 axis. We found that PLLP was downregulated in GC (p < 0.05). PLLP interacts with TRIM59, inhibits TRIM59-mediated ubiquitination degradation of p53, and inhibits the progression of GC cells with WT p53. PLLP may be used as a potential biomarker for targeted therapy of GC.
Sinusoidal capillarization - key symptoms of liver fibrosis progression - represents potential therapeutic targets. tRNA modification-mediated tRNA-derived small RNAs (tsRNAs) play a role in angiogenesis. NSun2, an RNA methyltransferase, generates a significant number of tsRNAs. However, the role of NSun2 and its mediated tsRNAs in liver fibrosis remains unclear. In this study, NSun2 deficiency was found to inhibit sinusoidal capillarization, alleviating liver fibrosis. Furthermore, endothelial cell angiogenesis and migration were disrupted in NSun2 knockout mice. Mechanistically, reduced NSun2 expression led to alterations in the functional tsRNAs tRF-1-S25 and tRF-5-V31, which regulate sinusoidal capillarization by targeting key proteins, including DUSP1 and FAK - crucial clinical targets. Moreover, intravenous injection of tRF-1-S25 and tRF-5-V31 inhibitor rescued liver fibrosis in mice. In conclusion, tsRNAs generated by NSun2-mediated modification of tRNAs inhibit sinusoidal capillarization. Furthermore, targeting the DUSP1/FAK/p-FAK pathway offers an innovative approach to treat this disease.
Background: Breast cancer has become the most frequently diagnosed cancer in the world. Detection at an early stage, frequently allows women to benefit from breast conserving surgery. However, some patients are not satisfied with the breast shape after breast-conserving surgery, and autologous tissue flaps are needed to fill the defect in the resection area. The modified lateral thoracic artery perforator (LTAP) flap isn't one of the commonly used flaps in breast surgery and has the advantages of a reliable blood supply, simple operation and few postoperative complications. In this study, we aimed to evaluate the feasibility and effectiveness of a modified LTAP flap for repairing partial breast defects after breast-conserving surgery. Methods: In this study, we retrospectively analyzed the clinical data of 126 patients treated with LTAP flaps to repair local breast defects at Affiliated Hospital of Guangdong Medical University between January 2020 and June 2021. Data were collected on the demographic characteristics of these patients, tumor size and location, type of axillary lymph node surgery, availability of adjuvant chemotherapy and radiotherapy, and postoperative complications. Results: The median weight of the tumor specimen was 185 g (range, 170-320 g), and this glandular tissue accounted for 30% to 40% of the total breast volume. The average flap size was 10.5 cm x2.5 cm (length range, 8-15 cm, width range: 2-4 cm). The minimum follow-up time was 6 months, with an average of 10 months (range, 6-22 months). The mean operative time was 130 minutes (range: 90-180 minutes), and the mean hospital stay was 3 days (range, 2-5 days). All modified LTAP flaps survived completely without donor site complications. None of the patients required revision surgery on the postoperative breast. Conclusions: The modified LTAP flap is a reliable method for repairing partial breast defects after breastconserving surgery. It has the advantages of a simple operation, a reliable blood supply, fewer postoperative complications, and a high flap survival rate. It is especially suitable for Asian women with small breast volumes and can achieve good breast contouring effects.
The interplay between intestinal barrier degradation and trace element insufficiency worsens inflammatory bowel disease (IBD). Selenium (se) is essential for glutathione peroxidase 4 (GPX4) synthesis, which protects against intestinal epithelial cell injury in IBD. However, malnutrition and malabsorption limit the availability of dietary selenium. This study investigated the protective effects of naturally occurring seleno-amino acids on the intestinal barrier in an IBD animal model by promoting GPX4 synthesis. L-se-methylselenocystine (seMc) supplementation reversed decreased GPX4 expression levels, alleviated glutathione depletion and scavenged reactive oxygen species in vitro. In vivo, enteral nutrition combined with seMc protected the intestinal barrier and alleviated IBD-related symptoms by inhibiting ferroptosis and reversing lipid peroxidation in epithelial cells while reducing immune cell infiltration. Our findings suggest that seleno-amino acid-based nutritional formulations may provide a basis for nutritional support to alleviate complex cycles between intestinal barrier damage and malnutrition in IBD patients.
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Intestinal mucosal barrier aging is a major cause of the occurrence and development of many chronic diseases in older adults and is closely associated with gut microbiota. However, it remains unclear whether exogenous supplementation with omega‐3 polyunsaturated fatty acids (ω‐3 PUFAs) can ameliorate aging‐induced intestinal mucosal barrier damage by regulating the gut microbiota. This study was conducted to explore the roles of ω‐3 PUFAs and gut microbiota in the process of maintaining the intestinal mucosal barrier. Senescence‐accelerated mouse prone 8 (SAMP8) mice were used to establish a geriatric animal model and given reasonable doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplemented diets for six months to validate the effect of ω‐3 PUFAs. Differences in the composition and function of gut microbiota were analyzed using 16S rRNA gene sequencing. This study revealed that aging SAMP8 mice showed increased intestinal permeability and gut microbiota disorder. Long‐term supplementation with ω‐3 PUFAs reduced intestinal mucosal permeability (P < 0.05), regulated gut microbiota, strengthened the microecological interactions, and enhanced enrichment of metabolic pathways producing short‐chain fatty acids (P < 0.05), ultimately ameliorating intestinal mucosal barrier dysfunction. Furthermore, we demonstrated that ω‐3 PUFAs could maintain the aging intestinal mucosal barrier by regulating the relative abundance of eight key characteristic microbial strains to increase the concentration of DHA and EPA in the plasma and colon tissue and reduced intestinal permeability of SAMP8 mice. ω‐3 PUFAs can significantly ameliorate intestinal mucosal barrier function in senescence‐accelerated mice, and this effect is mediated by the gut microbiota. The findings of our study provide a scientific basis for the rational intake of ω‐3 PUFAs in older adults to maintain intestinal mucosal barrier function.
The aim of this study is to explore a novel classification and investigate the clinical significance of hepatocellular carcinoma (HCC) cells. We analyzed integrated single-cell RNA sequencing and bulk RNA-seq data obtained from HCC samples. Cell trajectory analysis divided HCC cells into three subgroups with different differentiation states: state 1 was closely related to phosphoric ester hydrolase activity, state 2 was involved in eukaryotic initiation factor 4E binding, translation regulator activity and ribosome, and state 3 was associated with oxidoreductase activity and metabolism. Three molecular classes based on HCC differentiation-related genes (HDRGs) from HCC samples were identified, which revealed immune checkpoint gene expression and overall survival (OS) of HCC patients. Moreover, a prognostic risk scoring (RS) model was generated based on eight HDRGs, and the results showed that the OS of the high-risk group was worse than that of the low-risk group. Further, potential therapeutic drugs were screened out based on eight prognostic RS-HDRGs. This study highlights the importance of HCC cell differentiation in immunotherapy, clinical prognosis, and potential molecular-targeted drugs for HCC patients, and proposes a direction for the development of individualized treatments for HCC.
Abstract Background The scored Patient-Generated Subjective Global Assessment (PG-SGA) has been widely used to assess the nutritional status of cancer patients. The purpose of this study is to compare the differences in PG-SGA scores and the 7 domain scores of the PG-SGA in male and female cancer patients. Methods This study was conducted at 72 hospitals from July 2013 to December 2018, a part of the Investigation on Nutritional Status and its Clinical Outcomes of Common Cancers. The PG-SGA was recorded to evaluate the nutritional status of patients. A total of 19,528 patients with 13 common malignancies were included in this study. Student t test and the χ2 test were applied to analyze the sex differences in the 7 domain scores. The Cancer Genome Atlas (TCGA) database was used to analyze the expression levels of symptom-related genes. Results There were significant sex differences in the PG-SGA (P = 0.032), notably in patients with gastric cancer (male vs female: 9.09 ± 4.86 vs 9.58 ± 5.07, P = 0.005) and esophageal cancer (9.64 ± 4.90 vs 10.46 ± 4.96, P = 0.011) and the average total PG-SGA of female patients was slightly higher than that of male patients (7.64 ± 4.98 vs 7.77 ± 5.14). The differences were mainly related to the weight, eating, symptom, as well as activity and physical function scores in the stratified analysis. Possible causes of the sex differences were the rates of nausea, vomiting, dry mouth, and other symptoms, in both gastric and esophageal cancer patients. Analysis of the TCGA database suggested that most of the related genes were sex neutral, except for genes related to dysphagia in gastric cancer (VEGFC was higher in female patients, VEGFA and VEGFB higher in male patients). Conclusions There are sex differences in the PG-SGA scores in patients with various tumor types (female patients generally had higher scores than male patients), with differences mainly in the weight, eating, symptom, as well as activity and physical function scores. The sex differences in PG-SGA scores might be due to the differences in the clinical manifestations of the disease, and further studies should be carried out to investigate other factors influencing the PG-SGA scores in cancer patients. This study provides basic data supporting the individualized nutritional treatment of cancer patients in clinical practice.
Background:Breast cancer is the most common gynecological malignancy and the leading cause of cancer-related deaths in women. P-element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are novel non-coding RNAs whose abnormal expressions have been closely associated with multiple cancers. This study explored the roles and possible mechanisms of piRNA-31106 in breast cancer.Methods:The expression of piRNA-31106 in breast cancer tissues and cells was detected by reverse transcription polymerase chain reaction (RT-PCR). The pcDNA vector containing piRNA-31106 (pcDNA-piRNA-31106) and a short hairpin (sh)RNA containing piRNA-31106 (shRNA-piRNA-31106) were used to interfere with piRNA-31106 expression in breast cancer cells. The effects on cell proliferation, apoptosis/cell cycle, invasion, and metastasis were detected via Cell Counting Kit-8 (CCK-8), flow cytometry, transwell assays, and scratch tests, respectively. The protein expressions of murine double minute 2 (MDM2), cyclin-dependent kinase 4 (CDK4), and cyclinD1 were detected by Western blot analysis. The N6-methyladenosine (m6A) RNA methylation level and the binding relationship between piRNA-31106 and METTL3 were analyzed. The role of METTL3 in the regulation of breast cancer by piRNA-31106 was further analyzed by using small interfering (si)RNA targeting METTL3.Results:PiRNA-31106 was highly expressed in breast cancer tissues and cell lines MDA-MB-231 and MCF-7. Overexpression of piRNA-31106 promoted the viability, invasion, and migration of breast cancer, inhibited apoptosis, and promoted the expressions of MDM2, CDK4, and cyclinD1. Inhibition of piRNA-31106 showed the opposite effect. In addition, piRNA-31106 promoted the m6A methylation levels and facilitated methyltransferase-like 3 (METTL3) expression in MDA-MB-231 and MCF-7 cells. RNA immunoprecipitation (RIP) assays confirmed the binding relationship between piRNA-31106 and METTL3. Further experiments demonstrated that si-METTL3 could inhibit the regulatory effects of piRNA-31106 on breast cancer.Conclusions:PiRNA-31106 was significantly highly expressed in breast cancer and could promote breast cancer progression by regulating METTL3-mediated m6A RNA methylation.
Background: To summarise data from previous reports and perform a meta-analysis to compare the short-term surgical outcomes and post-operative recovery between single-incision and multi-port laparoscopic distal gastrectomy (MLDG) for gastric cancer. Methods: A systematic literature search was performed using PubMed and Embase databases and relevant data were extracted. Short-term surgical outcomes and post-operative recovery of single-incision laparoscopic distal gastrectomy (SLDG) and MLDG for gastric cancer were compared using a fixed or random-effect model. Results: In total, we identified five relevant studies involving 983 participants for this systematic review and meta-analysis, and 45.8% (450/983) of patients underwent SLDG. The results demonstrated that mean operation time (weighted mean difference [WMD]:-3.22, 95% confidence interval [CI]: 14.64,8.19, P = 0.580; I2 = 75.6%), intra-operative blood loss (WMD:-19.77, 95% CI: 40.20,0.65, P = 0.058; I2 = 85.0%) and lymph node yield (WMD:-0.71, 95% CI: 1.47, 0.05, P = 0.068; I2 = 0%) of SLDG were comparable to those of MLDG for gastric cancer. In addition, SLDG had a similar incidence of post-operative complications compared with MLDG (odds ratio: 0.82, 95% CI: 0.55-1.22, P = 0.326; I2 = 0%). There was no significant difference between the two surgical procedures for the conversion to open surgery (OR: 0.32, 95%CI: 0.03-3.15, P = 0.331; I2 = 0%), the length of hospital stay (WMD:-0.05, 95% CI: 0.65, 0.55, P = 0.876; I2 = 44.1%), the time to first flatus (WMD:-0.24, 95% CI: 0.58, 0.10, P = 0.169; I2 = 85.3%) and the time to oral intake (WMD:-0.05, 95% CI: 0.20, 0.10, P = 0.500; I2 = 0%). Conclusion: Single-incision laparoscopic gastrectomy may be technically feasible and safe for gastric cancer. However, it did not show a more obvious advantage over MLDG.
Background Malnutrition is common in patients with cancer, and this adversely affects the survival and quality of life of patients. Chinese Society for Nutritional Oncology issued a multi-center, large-scale, long-term follow-up prospective study, the Investigation on Nutrition Status and Clinical Outcome of Patients with Common Cancers in China(INSCOC study) since 2013. This is an extension to the previous 2013-2020 study protocol. This study still sought to:(1) address the prognostic impact of nutritional factors and quality of life on cancer patient survival;(2) describe the overall and cancer-specific incidence and/or distribution of malnutrition and different measurements of patient quality of life. Methods and study design This is an observational, multi-centered, hospital-based prospective cohort study. Data collection will be performed at baseline(within 48 hours after patient admission), during the hospital stay and 30 days after hospital admission. Follow-up will be conducted for 1-20 years after enrollment. The primary outcome will be the all-cause mortality/overall survival, and secondary outcomes will be the length of hospital stay and costs of hospitalization. Study factors will include demographic characteristics, tumor characteristics, information about chronic diseases, hematological measurements(e.g., red blood cell count, total lymphocyte counts, hemoglobin,albumin, prealbumin, creatinine, C-reactive protein, IL-6), anthropometric measurements(e.g., height, weight, arm circumference, arm muscle circumference, triceps skinfold thickness, and waist circumference), body composition parameters, PG-SGA scores, quality of life(as indicated by the QLQ-C30 questionnaire), muscle mass(as indicated by the calf circumference), muscle strength(as indicated by the handgrip strength), muscle function(as indicated by the six-meter walking speed test) and physical status assessments(as indicated by the Karnofsky Performance Status scores). This clinical study protocol was approved by local Ethics Committees of all the participating hospitals. Written informed consent is required for each subject included. Discussion This multi-center, large-scale, long-term followup prospective study will help improve the diagnosis of malnutrition in cancer patients and identify the risk factors associated with adverse clinical outcomes. The anticipated results of this study will highlight the need for a truly scientific appraisal of nutrition therapy in Chinese oncology populations, and finally help treat the potentially reversible elements of malnutrition in cancer patients to improve their clinical outcomes in the future.
Background Malnutrition is common in patients with cancer, and can negatively impact their quality of life(QoL) and even survival. However, there is currently no large data available on the prevalence of malnutrition in Chinese cancer patients. This study evaluated the prevalence of malnutrition and the QoL of Chinese patients with locoregional, recurrent or metastatic cancer. Methods We conducted a nationwide observational, multi-center, hospital-based cross-sectional study within the Chinese Society of Nutritional Oncology(CSNO) Network. All of the patients were diagnosed with one of the following 18 different types of malignant tumors: lung cancer, gastric cancer, liver cancer, colorectal cancer, breast cancer, esophageal cancer, cervical cancer, endometrial cancer, nasopharyngeal carcinoma, malignant lymphoma, leukemia, pancreatic cancer, ovarian cancer, prostate cancer, bladder cancer, brain cancer, biliary tract malignant tumors or gastrointestinal stromal tumors. These patients were enrolled from 72 hospitals located in different regions of China. The patients’ nutritional status was evaluated based on the body mass index(BMI), loss of bodyweight, laboratory measurements and patient generated-subjective global assessment(PGSGA) scores. The cancer patients’ physical status and QoL were assessed by the Karnofsky Performance Status(KPS) questionnaire and the European Organization for Research and Treatment of Cancer(EORTC) QLQ-C30 questionnaire, respectively. Results From December 2013 to April 2016, 23,994 patients hospitalized for cancer treatment(such as surgery, chemotherapy or radiotherapy) were enrolled in the study. The patients included 12,494(52.9%) males and 11,124(47.1%) females. The mean age was 55.8±13.7 years. The proportions of patients in cancer stages Ⅰ, Ⅱ, Ⅲ, Ⅳ and uncertain were 11.5%, 20.3%, 27.5%, 30.2% and 10.5%, respectively. Among the 23,994 inpatients, the proportions of patients who were underweight(BMI < 18.5 kg/m~2), normal(18.5 kg/m~2 < BMI < 24 kg/m~2), overweight(24 kg/m~2 ≤ BMI < 28 kg/m~2) and obese(BMI ≥ 28 kg/m~2) were 9.3%, 59.9%, 26.1% and 4.7%, respectively. A total of 18.3%(4,101/22,424) of patients had lost 5% or more of their bodyweight within the past month and 19.6%(2,463/12,538) of patients had lost 10% or more of their bodyweight within the past 6 months. According to the PG-SGA scores, 26.6% of the patients were severely malnourished(score ≥ 9), 31.3% were moderately malnourished(scores 4~8). A total of 22.2% of patients had a serum albumin level lower than 35 g/L. Only 8.6%(2056/23,991) of the patients had severe KPS scores(≤ 60). The patients with these severe KPS scores were most frequently among those with cancers of the brain(19.7%), prostate(18.0%), pancreas(15.5%) and bladder(15.0%). Based on the QLQ-C30 score, 11.6% of patients had a poor QoL. The PG-SGA score and global QoL were correlated(r =-0.593, P < 0.001). Conclusion The prevalence of malnutrition in patients with cancer is relatively high, and is related to a poorer QoL. The present findings should be kept in mind when assessing cancer patients, because addressing the patient’s problems in nutritional status would be expected to improve both the clinical outcomes and QoL in cancer patients with malnutrition.
Tumor microenvironment (TME) has been demonstrated to exhibit a regulatory effect on the progressions of gastric cancer (GC). However, the related functions of stromal and immune components (TME-associated genes) in TME remain largely unclear. From the TCGA dataset, we downloaded the clinical data of 375 GC cases and then estimated the percentage of tumor-infiltrating immunocytes (TICs) and the levels of immune and stromal constituents by the use of CIBERSORT and ESTIMATE tolls. Univariate assays were applied to study the differentially expressed genes. The associations between the clinical information of GC patients and the expressions of the specific genes were analyzed based on the TCGA datasets. The effect of Plexin domain containing 2 (PLXDC2) expression on TICs was conducted. We observed that PLXDC2 expression was distinctly upregulated in GC specimens compared with nontumor gastric specimens. Its upregulation was associated with advanced clinical stages and predicted a shorter overall survival of GC patients. The genes in the group of higher expressing PLXDC2 were primarily enriched in immunity-associated events. By the use of CIBERSORT, we observed that PLXDC2 expressions were related to the proportion of dendritic cells resting, T cell CD4 memory resting, eosinophils, mastocyte resting, mononuclear cells, plasma cells, T cell follicle helper, macrophage M2, and dendritic cells activated. Overall, our discoveries revealed that the expression of PLXDC2 was remarkable in GC, might be a possible biomarker for GC, and provided novel contents regarding immune infiltrates, offering novel insight for treatments of GC.
BACKGROUND:Early oral feeding (EOF) is an important measure for early recovery of patients with gastrointestinal tumors after surgery, which has emerged as a safe and effective postoperative strategy for improving clinical outcomes. AIM:To determine the safety and efficacy of early oral feeding in postoperative patients with upper gastrointestinal tumor. METHODS:This meta-analysis was analyzed using Review Manager version 5.3 and Stata version 14. All clinical studies that analyzed efficacy and safety of EOF for postoperative patients with upper gastrointestinal tumor were included. RESULTS:Fifteen studies comprising 2100 adult patients met all the inclusion criteria. A significantly lower risk of pneumonia was presented in the EOF compared with TOF group [relative risk (RR) = 0.63, 95% confidence interval (CI): 0.44-0.89, P = 0.01]. Length of hospital stay was significantly shorter in the EOF group than in the TOF group [weighted mean difference (WMD) = -1.91, 95%CI: -2.42 to -1.40; P < 0.01]. Cost of hospitalization was significantly lower (WMD = -4.16, 95%CI: -5.72 to -2.61; P < 0.01), and CD4 cell count and CD4/CD8 cell ratio on postoperative day 7 were significantly higher in the EOF group than in the TOF group: CD4 count (WMD = 7.17, 95%CI: 6.48-7.85; P < 0.01), CD4/CD8 ratio (WMD = 0.29, 95%CI: 0.23-0.35; P < 0.01). There was no significant difference in risk of anastomotic leak and total postoperative complications. CONCLUSION:EOF as compared with TOF was associated with lower risk of pneumonia, shorter hospital length of stay, lower cost of hospitalization, and significantly improved postoperative immune function of patients.
Alzheimer’s disease (AD) is a dementia-related disease with cognitive deterioration and memory impairment. Catalpol was reported to relieve impairments in learning and memory. The present study assessed the functional mechanism of catalpol in AD via miR-124/STIM2-mediated mitochondrial function. Primary hippocampal neurons were isolated and cultured. AD cell model was induced by Aβ 1−42 and treated with catalpol. APP/PS1 mouse model was established and treated with catalpol and miR-124 agomir. Aβ 1−42 induced mitochondrial damage and reactive oxygen species (ROS) generation in AD cell model. Catalpol alleviated mitochondrial damage and reduced ROS generation in hippocampal neurons. miR-124 was highly expressed in AD cell model and catalpol inhibited miR-124 expression. Catalpol alleviated Aβ 1−42 induced mitochondrial damage and ROS generation in hippocampal neurons by inhibiting miR-124 expression. miR-124 overexpression after catalpol treatment promoted mitochondrial damage and ROS generation in hippocampal neurons. miR-124 targeted STIM2. Silencing STIM2 after catalpol treatment promoted mitochondrial damage and ROS generation in hippocampal neurons. Catalpol slowed AD progression via the miR-124/STIM2 axis in vivo . The results of the present study indicated that catalpol alleviated mitochondrial damage and ROS generation and thus attenuated AD by regulating miR-124-mediated STIM2.
Background: This study aimed to clarify the relationship between F. nucleatum levels and the prognosis of CRC, which is still controversial. Methods: Relevant articles were searched on PubMed, Web of Science, PMC and Embase up to April 7, 2020. Outcomes of interest included clinical characteristics, molecular characteristic and survival analysis. HR (OR), odds ratios (OR) and 95% confidence interval (CI) were calculated to explore the prognostic value and relationship of clinical characteristics of Fusobacterium nucleatum in CRC. Results: A total of 3626 CRC patients from 13 eligible studies were included. High levels of F. nucleatum were associated with worse prognosis, as such parameters as overall survival (OS) (hazard ratio [HR] = 1.40, 95% confidence interval [CI]: 1.40 - 1.63, P < 0.0001), disease-free survival (DFS) (HR = 1.71, 95% CI: 1.29-2.26, P = 0.0002), and cancer-specific survival (OR= 1.93, 95% CI: 1.42-2.62, P <0.0001). F. nucleatum levels were related with T3-T4 stage (OR = 2.20, 95% CI: 1.66-2.91, P < 0.00001), M1 stage (OR = 2.11, 95% CI: 1.25-3.56, P = 0.005), poor tumor differentiation (OR = 1.83, 95% CI: 1.11-3.03, P =0.02), microsatellite instability-high (OR = 2.53, 95% CI: 1.53-4.20, P = 0.0003), and KRAS mutation (OR =1.27, 95% CI: 1.00-1.61, P=0.05) showed. Conclusions: High levels of F. nucleatum suggest a poor prognosis and are associated with tumor growth, distant metastasis, poor differentiation, MSI-high, and KRAS mutation in CRC patients.
Background and purpose: Obesity is becoming a major global health issue and is mainly induced by the accumulation of adipose tissues mediated by adipogenesis, which is reported to be regulated by peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer-binding protein α (C/EBPα). Trichostatin A (TSA) is a novel histone deacetylase inhibitor (HDACI) that was recently reported to exert multiple pharmacological functions. The present study will investigate the inhibitory effect of TSA on adipogenesis, as well as the underlying mechanism. Methods: The adipogenesis of 3T3-L1 cells was induced by stimulation with a differentiation cocktail (DMI) medium for 8 days. MTT assay was used to measure the cell viability and Oil Red O staining was used to evaluate the adipogenesis of 3T3-L1 cells. The total level of triglyceride and released glycerol were detected to evaluate the lipolysis during 3T3-L1 adipogenesis. The expression levels of Leptin, fatty acid-binding protein 4 (FABP4), and sterol regulatory element-binding protein (SREBP1C) were determined by qRT-PCR. qRT-PCR assay was utilized to detect the expression levels of PPARγ and C/EBPα in 3T3-L1 cells. A high-fat diet (HFD) was used to construct an obese mice model, followed by the treatment with TSA. HE staining was conducted to evaluate the pathological state of adipose tissues. Body weights and the weights of adipose tissues were recorded to evaluate the anti-obesity property of TSA. Results: Firstly, the promoted lipid accumulation induced by DMI incubation was significantly reversed by the treatment with TSA in a dose-dependent manner. The elevated expression levels of Leptin, FABP4, SREBP1C, PPARγ, and C/EBPα induced by the stimulation with DMI incubation were dramatically inhibited by the introduction of TSA, accompanied by the upregulation of phosphorylated AMP-activated protein kinase (p-AMPK). Secondly, the inhibitory effect of TSA against the expression level of PPARγ and lipid accumulation was greatly abolished by an AMPK inhibitor. Lastly, the increased body weights and visceral adipocyte tissue weight, as well as the enlarged size of adipocytes induced by HFD were pronouncedly reversed by the administration of TSA. Conclusion: TSA inhibited adipogenesis in 3T3-L1 preadipocytes by activating the AMPK pathway.
Background: MiRNAs play an important role in the development of colorectal cancer (CRC); however, there is little evidence of miRNAs in the screening of the nutritional risks of patients with CRC. Objectives: This study aimed to explore the role of preoperative miR-149 in nutritional screening of patients with CRC, and its associations with clinicopathological characteristics and postoperative complications of patients with CRC. Methods: The associations of serum miR-149 with clinicopathological characteristics and postoperative complications of patients were analyzed in this study. The receiver operating characteristic curves were plotted with miR-149 as the test variable, the grouping results of the patients with nutritional risks (total NRS2002 score >= 3 points), and no nutritional risks (total NRS2002 score <3 points) based on the preoperative NRS2002 score as the state variables. The consistency of miR-149 and NRS2002 in the nutritional screening of CRC was analyzed using the Kappa test. Results: MiR-149 was low in patients with CRC. There was a statistically significant difference in the miR-149 expression among patients with different tumor diameters and TNM stages in the two groups. The preoperative total NRS2002 score of CRC patients was <3 (without nutritional risks) in 271 cases, and >= 3 (with nutritional risks) in 129 cases. The sensitivity and specificity of miR-149 in the diagnosis of nutritional risks were 76.74% and 84.50%, respectively. The Kappa value was 0.622 with miR-149=3.095 as the critical value. Conclusion: MiR-149 can reflect the preoperative nutritional status of patients with CRC, and miR-149=3.095 can be used as the cut-off point for nutritional risk screening of patients with CRC, which is an important index for assessing the nutritional risk in the preoperative period. The expression of miR-149 has a certain association with postoperative complications.
The activation of glial cells may cause inflammatory responses to brain, leading to cognitive dysfunction. Green tea polyphenols have been reported to be neuroprotective. This study used the method of intracerebroventricular injection of A1-42 to establish an Alzheimer's disease (AD) model, and then treated with tea polyphenols. We aimed to investigate the effects and molecular mechanism of tea polyphenols on antagonizing the neurotoxicity induced by A1-42. Three-month-old male C57BL/6J mice were injected with A1-42 into the lateral ventricle and tea polyphenols were administered immediately after modeling. Morris water maze test was conducted to detect the cognitive function, Western blot assay was used to detect protein expressions of related signaling pathways in hippocampus tissue, and immunofluorescence assay was used to label microglia and astrocyte. Compared with AD model mice without tea polyphenols treatment, the latency to find the hidden platform of AD model mice with tea polyphenols treatment was significantly reduced, and the proportion of time spent in the quadrant was significantly increased. The expressions of BDNF and TrkB were significantly increased. In addition, microglia/astrocyte cell proliferation was significantly reduced and the activation of pro-inflammatory signaling pathway factors was down-regulated, while anti-inflammatory signaling pathway factors was up-regulated. This study indicates that tea polyphenols attenuate A1-42-induced cognition dysfunction and the effects may be related to hippocampal neurogenesis and glial cell-related inflammatory response.
Background: The optimal timing of surgery for left-sided mild-to-moderate congenital diaphragmatic hernia (CDH) remains unknown. Objectives: To determine the optimal timing of surgery for left-sided mild-to-moderate CDH. Methods: Thirty newborns were randomly divided into emergency (EAR) and delayed (DEL) surgery groups. Thoracoscopic repair of CDH was performed within 48 hours after birth in the EAR group and then in the DEL group. Next, the baseline data, primary and secondary endpoints, and adverse reactions were assessed. Results: Differences between the two groups were not significant in terms of the measured lung-to-head ratio (LHR), preoperative pulmonary artery hypertension (PAH)-free/mild PAH ratio, surgery duration, duration of postoperative mechanical ventilation, incidence of postoperative moderate-to-severe PAH, postoperative mortality, and recurrence rate in the follow-up (P > 0.05 for all). Meanwhile, age at surgery (P = 0.001), duration of fasting (P = 0.001), and hospital stay (P = 0.032) were significantly different between the two groups. Conclusions: Timing of thoracoscopy, performed within 85 hours of birth for left-sided CDH repair, does not affect the therapeutic outcomes of children with left-sided mild-to-moderate CDH.