Titin as a potential novel therapeutic target in colorectal cancer.

Colorectal cancer (CRC) is identified as a primary cause of death around the world. The current chemotherapies are not cost-effective. Therefore, finding novel potential therapeutic target is urgent. Titin (TTN) is a muscle protein that is critical in hypertrophic cardiomyopathy. However, its role in CRC is not well understood. The study focused on exploring the possible role of TTN in CRC carcinogenesis. TTN mRNA and protein expression levels presented an obvious downregulation in CRC tissue samples, relative to normal control (p < 0.05). TTN expression significantly correlated with the clinical stage (normal vs. Stage 1, p < 0.05; normal vs. Stage 4, p < 0.05), node metastasis (normal vs. N1, p < 0.05; N1 vs. N2, p < 0.05), histological type (normal vs. adenocarcinoma, p < 0.05), race (Caucasian vs. Asian, p < 0.05; African-American vs. Asian, p < 0.05) and TP53 mutation (normal vs. TP53 mutation, p < 0.05), considering The Cancer Genome Atlas database. However, for patients who had higher TTN expression, the overall survival was remarkably shorter than patients who had low TTN expression. Furthermore, TTN was lowly expressed in four CRC cell lines. TTN overexpression facilitated CRC cells in terms of the proliferation, metastasis and invasion. Based on gene set enrichment analysis, the ERB pathway might be responsible for TTN-related CRC. Besides, TTN was involved in the response to azacitidine. Overall, TTN might serve as a potential novel therapeutic target for treating and overcoming chemotherapy resistance in CRC.

Precision treatment of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous tumor comprising pancreatic cancer cells, fibroblasts, immune cells, vascular epithelial cells, and other cells in the mesenchymal tissue. PDAC is difficult to treat because of the complexity of the tissue components; therefore, achieving therapeutic effects with a single therapeutic method or target is problematic. Recently, precision therapy has provided new directions and opportunities for treating PDAC using genetic information from an individual's disease to guide treatment. It selects and applies appropriate therapeutic methods for each patient, with an aim to minimize medical damage and costs, while maximizing patient benefits. Molecular targeted therapy is effective in most clinical studies; however, it has been ineffective in large-scale randomized controlled trials of PDAC, mainly because the enrolled populations were not stratified on a molecular basis. Molecular stratification allows the identification of the PDAC population being treated, optimizing therapeutic effect. However, a systematic review of precision therapies for patients with highly heterogeneous PDAC backgrounds has not been conducted. Here, we review the molecular background and current potential therapeutic targets related to PDAC and provide new directions for PDAC precision therapy.

Tong-Xie-Yao-Fang induces mitophagy in colonic epithelial cells to inhibit colitis-associated colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Based on the core pathogenesis of hepatosplenic disorder and qi transformation disorder in ulcerative colitis, Tong-Xie-Yao-Fang (TXYF) is a classical traditional Chinese medicine commonly used to treat ulcerative colitis. Our study revealed that it has the potential to prevent colitis-associated colorectal cancer, which embodies the academic concept in traditional Chinese medicine of treating the disease before it develops. AIM OF THE STUDY: This study was aimed at evaluating the therapeutic role of TXYF in treating colitis-associated colorectal cancer and exploring its possible underlying mechanisms. MATERIALS AND METHODS: A colitis-associated colorectal cancer model was established in mice using azoxymethane and dextran sulfate sodium salt to examine the therapeutic effect of TXYF. The mouse body weights were observed. Hematoxylin-eosin staining was used to evaluate mouse colon histopathology. Colon cancer cells and colon epithelial cells were used to explore the potential molecular mechanisms. The proliferation and apoptosis of cells were detected by CCK8 and cell colony assays, flow cytometry and western blotting. The epithelial-mesenchymal transition (EMT) and mitophagy markers were examined by immunohistochemistry, western blotting, quantitative real-time PCR and immunofluorescence staining. RESULTS: TXYF inhibited the tumorigenesis of mice with colitis-associated colorectal cancer and the growth of inflammatory colon cells. TXYF induced mitophagy in colon cancer cells through the PTEN-induced putative kinase 1 (PINK1)/Parkin pathway to reverse EMT, which was consistent with the results in mice with colitis-associated colorectal cancer. CONCLUSIONS: The results of the present study demonstrated that TXYF effectively inhibited the progression of colitis-associated colorectal cancer through the PINK1/Parkin pathway, which provides new evidence for prevention strategies for this disease.

IL6ST: A Novel Therapeutic Target for Managing and Treating Colorectal Cancer Via Ferroptosis.

Inflammation is an essential driver of colorectal cancer (CRC). Identifying phenotypes and targets associated with inflammation and cancer may be an effective way to treat CRC. R was used to analyze interleukin 6 cytokine family signal transducer (IL6ST) expression in The Cancer Genome Atlas Colon Adenocarcinoma database. Immunohistochemistry, western blotting, and quantitative PCR were used to detect IL6ST and ferroptosis-related genes expression in our cohort. Receiver operating characteristic curves evaluated the specificity and sensitivity of IL6ST to predict CRC. Cell counting kit-8 investigated cell viability. Mitochondrial morphology, total iron, and reactive oxygen species (ROS) levels were evaluated to assess cell ferroptosis. The correlation of IL6ST and immune cells filtration were also analyzed based on R. IL6ST was significantly upregulated in CRC tissues (P < .05). The specificity and sensitivity of IL6ST for predicting CRC were high (area under the curve (AUC): 0.919, CI: 0.896-0.942). IL6ST was significantly associated with ferroptosis-related genes. IL6ST knockdown decreased SW480 cells viability (knockdown vs. vector, P = .004), promoted the ferroptosis phenotype, and increased iron accumulation (knockdown vs. vector P = .014) and ROS production (knockdown vs. vector P = .005). IL6ST upregulation increased SW620 cells viability (overexpression vs. blank, P = .001), inhibited the ferroptosis phenotype, and decreased iron accumulation (overexpression vs. vector P = 0.006) and ROS production (overexpression vs. vector P = .05). IL6ST increased FTH1 and GPX4 expression and reduced PTGS2, NOX1, and ACSL4 expression (P < .01). Additionally, IL6ST level is linked to immune cell infiltration. A higher enrichment score of T cells was observed in IL6ST up-regulated group. IL6ST inhibits ferroptosis and may be a potential novel therapeutic target in CRC via the modulation of ferroptosis.

Gastric duplication cysts: literature review and a case report of rare multiple gastric duplication cysts treated by endoscopic submucosal dissection.

Gastric duplication cysts (GDCs) are rare structural abnormalities, especially in adults. We first report a rare case of small multiple GDCs in a woman, which presents as a submucosal tumor (SMT) at the gastric antrum. In consideration of the patient's request for surgical treatment and minimally invasive resection, endoscopic submucosal dissection (ESD) was performed to remove the cyst. The case provides a reference for ESD surgery to remove small GDCs. So far, there is no consensus or practice guidelines for the diagnosis and management of GDCs. Herein we perform a comprehensive literature review and discussion on GDCs. GDCs are 'repetitive' cystic or tubular structures of gastric mucosa and muscularis mucosae, and share the muscularis propria and serous layer with the normal gastric wall. GDCs protruding into the stomach cavity can be diagnosed by endoscopic ultrasound (EUS), which has higher specificity and accuracy than CT and MRI. Some GDCs may cause complications, even cancerization. Therefore, we suggest that once found, the GDCs could be completely resected. For GDCs protruding into the stomach cavity, endoscopic surgery such as ESD can be adopted to remove the lesion. Endoscopic full-thickness resection (EFTR) may become an option for larger GDCs in the future. For extraluminal GDC, laparoscopic surgery is currently preferred. In this review, we summarized the structural and histopathological characteristics of GDCs and various treatment therapies, in order to provide experience and reference for the diagnosis and treatment of GDCs in the future.

Body Composition in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is associated with body composition changes, which are associated with clinical prognosis, response to therapy, and quality of life in IBD patients. Therefore, it is critical to review the body composition distribution in IBD, summarize the potential factors affecting body composition distribution, and take steps to improve the body composition distribution of IBD patients as early as possible. In the current review, we searched PubMed via keywords 'inflammatory bowel disease', or 'IBD', or 'Crohn's disease', or 'CD', or 'ulcerative colitis', or 'UC', and 'body composition'. Malnutrition and sarcopenia are common in IBD patients and are associated with the clinical course, prognosis, and need for surgery. Disease activity, reduced nutrition intake, vitamin D deficiency, and intestinal dysbiosis are factors contributing to changed body composition. Early use of biological agents to induce remission is critical to improving body composition distribution in IBD patients, supplementation of vitamin D is also important, and moderate physical activity is recommended in IBD patients with clinical remission.

Glutamine addiction and therapeutic strategies in pancreatic cancer.

Pancreatic cancer remains one of the most lethal diseases worldwide owing to its late diagnosis, early metastasis, and poor prognosis. Because current therapeutic options are limited, there is an urgent need to investigate novel targeted treatment strategies. Pancreatic cancer faces significant metabolic challenges, principally hypoxia and nutrient deprivation, due to specific microenvironmental constraints, including an extensive desmoplastic stromal reaction. Pancreatic cancer cells have been shown to rewire their metabolism and energy production networks to support rapid survival and proliferation. Increased glucose uptake and glycolytic pathway activity during this process have been extensively described. However, growing evidence suggests that pancreatic cancer cells are glutamine addicted. As a nitrogen source, glutamine directly (or indirectly via glutamate conversion) contributes to many anabolic processes in pancreatic cancer, including amino acids, nucleobases, and hexosamine biosynthesis. It also plays an important role in redox homeostasis, and when converted to α-ketoglutarate, glutamine serves as an energy and anaplerotic carbon source, replenishing the tricarboxylic acid cycle intermediates. The present study aims to provide a comprehensive overview of glutamine metabolic reprogramming in pancreatic cancer, focusing on potential therapeutic approaches targeting glutamine metabolism in pancreatic cancer.

Cytomegalovirus Pneumonia in Inflammatory Bowel Disease: Literature Review and Clinical Recommendations.

Aim: The objective was to elucidate the correlation between CMVP and immunosuppressive therapy in IBD patients, we hope this review could expand on the significance of CMV as an opportunistic pathogen and the potential impact on morbidity and mortality in IBD patients. Methods: Records and clinical trajectories linked to CMVP in IBD patients were extracted from the PubMed database, irrespective of language barriers. The reference lists incorporated in these studies were manually inspected. Conclusions were generated using straightforward descriptive analysis. Results: In total, 18 IBD patients, including Crohn's disease (CD, 67%) and Ulcerative Colitis (UC, 33%), affected by CMVP were identified from 17 published articles. A minority of these patients (17%) exhibited active disease, whereas the majority (83%) presented with quiescent disease. Fever (100%) and dyspnea (44%) emerged as the most prevalent clinical symptoms. All the patients had undergone immunosuppressive therapy. A significant proportion, up to 89%, had received thiopurine treatment prior to the CMVP diagnosis. Interestingly, none of the patients were subjected to biological therapy. Half of the patients manifested with Hemophagocytic Lymphohistiocytosis (HLH). Almost all patients (94%) were administered antiviral treatment and a substantial 83% experienced full recovery. Immunosuppressive agents were either tapered or discontinued altogether. A subset of patients, 17%, suffered fatal outcomes. Conclusion: Our findings underscore the need for heightened suspicion of CMVP in IBD patients who exhibit symptoms such as fever and dyspnea. During the COVID-19 pandemic, CMVP should be considered a potential differential diagnosis. It was observed that CMVP primarily transpires during CD remission. Azathioprine emerged as the predominant immunosuppressant linked to CMV reactivation. The prompt application of effective antiviral therapy can substantially enhance patient outcomes. CMV vaccine might serve as a viable prevention strategy.

The Novel LncRNA WASH5P Inhibits Colorectal Cancer Carcinogenesis via Targeting AKT Signaling Pathway.

Emerging evidence has shown that long non-coding RNAs (lncRNAs) play an important role in colorectal cancer (CRC) carcinogenesis, so more specific mechanisms of key lncRNAs in CRC initiation and development are needed. Here, we evaluated the expression profiles of lncRNAs in CRC tissues and identified a novel lncRNA generated from the pseudogene Wiskott-Aldrich syndrome protein (WASP) family homolog 5, termed lncRNA WASH5P. However, the role and potential molecular mechanism of this novel lncRNA in diseases, including CRC carcinogenesis, is unknown. Our present study found that WASH5P was significantly downregulated in CRC cell lines and tissues compared with normal controls. The ectopic expression of WASH5P in CRC cells could significantly inhibit CRC cell proliferation, invasion, and migration. In addition, WASH5P could increase the expression of E-cadherin and decrease Vimentin expression. WASH5P-overexpressing CRC cells developed tumors more slowly in different mouse models. Meanwhile, the overexpression of WASH5P could significantly inhibit AKT activation via suppressing AKT phosphorylation. The treatment of PI3K/AKT (phosphatidlinositol 3-kinase /protein kinase B) signaling agonist 740Y-P rescued WASH5P-reduced AKT phosphorylation and abolished the inhibitory effects of WASH5P on cell viability, migration, and invasion. Moreover, 740Y-P restored the WASH5P-induced downregulation of p-AKT and vimentin and the upregulation of E-cadherin via Western blot. In summary, our findings suggested that the novel lncRNA WASH5P might be a potential candidate biomarker and therapeutic target that could inhibit CRC by repressing the AKT signaling pathway.

CLEC4s as Potential Therapeutic Targets in Hepatocellular Carcinoma Microenvironment.

Immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC) is critical in tumor development. C-type (Ca2+ -dependent) lectin (CLEC) receptors, essential in innate pattern recognition, have potential regulatory effects on immune cell trafficking and modulatory effects on cancer cell activity. However, information on the expression and prognostic value of CLECs in HCC is scanty. Herein, we explored the potential role of CLECs in HCC based on TCGA, ONCOMINE, GEPIA, UALCAN, cBioPortal, Metascape, TRRUST, and TIMER databases. Results demonstrated a significantly higher mRNA level of CLEC4A and CLEC4L in HCC tissues than normal liver tissues. Contrarily, we found significantly low CLEC4G/H1/H2/M expression in HCC tissues. The IHC analysis revealed the following: Absence of CLEC4A/J/K/M in normal and liver cancer tissues; high CLEC4C expression in HCC tissues; low expression and zero detection of CLEC4D/E/H1/H2/L in HCC tissues and normal tissues, respectively. And the HepG2 and LX-2 were used to verify the expression level of CLEC4s via qRT-PCR in vitro. Furthermore, the expression of CLEC4H1 (ASGR1) and CLEC4H2 (ASGR2) exhibited a significant relation to clinical stages. However, the expression of CLEC4A, CLEC4D, CLEC4E, CLEC4J (FCER2), CLEC4K (CD207), CLEC4G, CLEC4H1, CLEC4M, and CLEC4H2 decreased with tumor progression. Patients expressing higher CLEC4H1/H2 levels had longer overall survival than patients exhibiting lower expression. Moreover, CLEC4A/D/E/J/K/G/H1/M/H2 had significant down-regulated levels of promoter methylation. The expression level of CLEC4s was correlated with the infiltration of B cells, CD8 + T cells, CD4 + T cells, macrophage cells, neutrophil cells, and dendritic cells. Functional analysis revealed the potential role of CLECL4s in virus infection, including COVID-19. Also, hsa-miR-4278 and hsa-miR-324-5p, two potential miRNA targets of CLEC4s, were uncovered. This article demonstrates that CLEC4 is crucial for the development of HCC and is associated with infiltration of various immune cells, providing evidence for new immunotherapy targets in HCC.

[Conducting clinical studies during the epidemics of communicable diseases: perspectives of methodology and health economics].

In the setting of epidemics of communicable diseases, early initiation of epidemiological and clinical data collection and analysis and conducting relevant researches are essential to the success of epidemic containment. The coronavirus disease 2019 (COVID-19), starting initially as an epidemic in China in late 2019 and now becoming a pandemic globally, poses grave challenges to the global health care systems while also provides an opportunity for studying infectious diseases in the perspective of methodology. The authors propose the evaluation methods for case reports, randomized controlled trials (RCTs), real-world evidence studies and health economics researches during an epidemic. Case reports, which are of important value for health care workers during outbreaks of infectious diseases, should be written in standard format and style and published following a strict peer review process. RCTs provides the gold standard for evaluating the effectiveness of a given treatment for the patients from the outbreaks. We review the potential challenges faced in conducting RCTs during the outbreaks. The real-world data collected from the cases in designated hospitals allow the verification of the safety and effectiveness of the intervention measures. The data from health economics research also provide important support for optimizing communicable disease prevention and control strategies. Herein we summarize the health economics research methods, study design, and technical points during the outbreaks. We recommend that clinical research and health economics research be incorporated into the prevention and control plan and measures be taken to ensure both the standards and feasibility of these studies to improve the response capacity against outbreaks of communicable diseases.

LncRNA MIR4435-2HG predicts poor prognosis in patients with colorectal cancer.

BACKGROUND: LncRNA MIR4435-2HG is observed in a variety of cancers, while its role in colorectal cancer is unknown. We aimed to demonstrate the relationship between MIR4435-2HG and colorectal cancer based on The Cancer Genome Atlas (TCGA) database. MATERIALS AND METHODS: Patients with colorectal cancer were collected from TCGA. We compared the expression of MIR4435-2HG in colorectal cancer and normal tissues with Wilcoxon rank sum test, and logistic regression was used to evaluate the relationship between MIR4435-2HG and clinicopathological characters. Moreover, Kaplan-Meier and Cox regression was performed to evaluate the correlation between MIR4435-2HG and survival rate. Gene set enrichment analysis (GSEA) was also conducted to annotate biological function of MIR4435-2HG. RESULTS: MIR4435-2HG level was elevated in colorectal cancer tissues. Increased level of MIR4435-2HG was significantly correlated with TNM stage (OR = 1.66 for T1/T2 vs. T3/T4; OR = 1.68 for N0 vs. N1/N2), stage (OR = 1.66 for stage 1/2 vs. stage 3/4), and carcinoembryonic antigen level before treatment (OR = 1.70 for <5 vs. ≥5) (all P-value <0.05). High MIR4435-2HG expression had a poorer progression-free survival (p = 0.048), and overall survival (OS) (P = 0.028), which were validated in the GSE92921 and GSE29621 datasets. MIR4435-2HG expression (P = 0.040, HR = 1.955 (95% CI [1.031-3.710])) was independently correlated with OS. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway, the cell surface interactions at the vascular wall, and integrin cell surface interactions were differentially enriched in MIR4435-2HG high expression phenotype. CONCLUSIONS: Increased MIR4435-2HG might be a potential biomarker for the diagnosis and prognosis of colorectal cancer. Moreover, MIR4435-2HG might participate in the development of colorectal cancer via the P38/MAPK and VEGF pathway.

Osteoporosis as an initial manifestation in a patient with Crohn's disease: A case report.

The present case report details a rare case of osteoporosis as the initial manifestation of Crohn's disease (CD). A 43-year-old male was referred to the Second Xiangya Hospital of Central South University (Changsha, China) for further examination of low back pain (LBP) without digestive symptoms. Bone mineral density (BMD) analysis indicated osteoporosis, particularly in the lumbar spine. Endoscopy revealed an inflamed and strictured ileocecal valve with less inflammation in the ascending, transverse colon, sigmoid colon and rectum, compatible with CD, which was in accordance with the appearance of an abdominal computed tomography scan. Duodenal-balloon enteroscopy indicated segmental ulceration and stricture in the jejunum, in accordance with CD. The patient was diagnosed with CD following examination. It was suspected that osteoporosis may be an extra-intestinal manifestation of CD. Steroids and biological agents were prescribed in sequence. LBP and BMD rapidly improved following treatment, and inflammatory markers returned to normal after 1.5 years of treatment. According to this case, osteoporosis with unknown causes should be considered as a possible sign of small intestinal CD.

Antitumor mechanisms of bifidobacteria.

Cancer remains one of the most common causes of mortality globally. Chemotherapy, one of the major treatment strategies for cancer, primarily functions by targeting the cancer cells and affecting them physiologically, but also affects normal cells, which is a major concern at present. Therefore, adverse effects of chemotherapy drugs, including myelosuppression and liver and kidney damage, are of concern. Now, microbial products have attracted attention in cancer treatment research. Notably, carcinogenesis is considered to be associated with microbial dysbiosis, particularly the positive antitumor effects of bifidobacteria. Although there remains a substantial amount to be understood about the regulation of bifidobacteria, bifidobacteria remain an attractive and novel source of cancer therapeutics. The present review focuses on introducing the latest information on the antitumor effects of bifidobacteria and to propose future strategies for using bifidobacteria in the development of cancer therapeutics.

Complications Following Stem Cell Therapy in Inflammatory Bowel Disease.

BACKGROUNDS: Pharmacotherapy and surgery constitute the mainstay of treatment for inflammatory bowel disease (IBD). But post-treatment relapsing and recurrence persist as concerns in patients with IBD. Stem cell therapy (SCT) has emerged as a promising treatment strategy in inflammatory bowel disease (IBD), including hematopoietic stem cells (HST), mensenchymal stem cells (MSCs). However, severe complications limit the clinical use of SCT in IBD. Therefore, this review aims to summarize SCT-associated complications, and illustrate possible prevention strategies. METHODS: We searched Pubmed for studies which reported the use of SCT to treat patients with IBD. Searching terms included 'IBD' or 'Inflammatory bowel disease' or 'CD' or 'Crohn's disease' and 'stem cell therapy' or 'stem cell transplantation'. RESULTS: HSCT can restore the immune tolerance following chemotherapy-induced immune ablation, and MSCs could affect immune cells or secret trophic factors to treat IBD. However, severe complications limit the clinical use of SCT in IBD. Dominant SCT-associated complications include infection, ectopic tissues, and graft-versus-host disease (GVHD), especially for auto-HSCT. As for infection, bacteremia and virus infection were found after SCT treatment, and the use of anti-microbial regimens could reduce incidences of infection. Ectopic tissue formation in the recipient was observed after treatment with HSCT or MSC. Homing and tissue integration might be the possible mechanisms for not forming ectopic tissues. In addition, GVHD was also observed in allogeneic HSCT. Therefore, autologous HSCT and MSCs transplantation were recommended to avoid GVHD. CONCLUSIONS: MSCs with their low immunogenicity property eliminate the need for chemotherapy, and are over HSCT in reducing the risk of severe complications. For better application of SCT in IBD, antimicrobial prophylaxis should be used combined with SCT.

Colorectal carcinoma masked by systemic inflammatory response syndrome: A case report.

The present study described the case of a 68-year-old woman who presented to the Second Xiangya Hospital of Central South University (Changsha, China) with progressive abdominal pain, distention and diarrhea. These symptoms were diagnosed as the initial manifestations of systemic inflammatory response syndrome associated with colorectal carcinoma (CRC). The presentation appeared as a common emergency medical case, which was eventually recognized as a CRC masked by this emergency symptom. This case highlights the fact that a correct diagnosis can be made by looking through the outward appearance to perceive the essence of the condition. Therefore, vigilant surveillance is of utmost importance in order to expedite prompt recognition and rapid management of this presentation of CRC.

In vivo and in vitro anti-sepsis effects of physcion 8-O-ß-glucopyranoside extracted from Rumex japonicus.

The present study was designed to investigate the anti-sepsis effects of physcion 8-O-ß-glucopyranoside (POG) isolated from Rumex japonicas and explore its possible pharmacological mechanisms. POG was extracted from R. japonicas by bioactivity-guided isolation with the anti-sepsis agents. Survival analysis in septic mouse induced by LPS and heat-killed Escherichia coli were used to evaluate the protective effect of POG (40 mg·kg-1, i.p.) on sepsis. Cytokines including TNF-α, IL-1ß and IL-6 in RAW 264.7 cells induced by LPS (100 ng·mL-1) were determined by ELISA. In addition, the proteins expressions of TLR2 and TLR4 were determined by Western blotting assay. Our results demonstrated that POG (40 mg·kg-1, i.p.) possessed significant protective activity on the endotoxemic mice. The POG treatment (20, 40, and 80 µg·mL-1) significantly decreased the TNF-α, IL-1ß and IL-6 induced by LPS (P < 0.01) in a concentration-dependent manner. Furthermore, the TLR4 and TLR2 proteins were also down-regulated by POG at 20 (P < 0.01), 40 (P < 0.01), and 80 µg·mL-1 (P < 0.01). The present study demonstrated that the POG extracted from R. japonicas possessed significant anti-sepsis effect on endotoxemic mice, and can be developed as a novel drug for treating sepsis in the future.

Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice.

AIM: To analyze the changes of different Lactobacillus species in ulcerative colitis patients and to further assess the therapeutic effects of selected Lactobacillus strains on dextran sulfate sodium (DSS)-induced experimental colitis in BALB/c mice. METHODS: Forty-five active ulcerative colitis (UC) patients and 45 population-based healthy controls were enrolled. Polymerase chain reaction (PCR) amplification and real-time PCR were performed for qualitative and quantitative analyses, respectively, of the Lactobacillus species in UC patients. Three Lactobacillus strains from three species were selected to assess the therapeutic effects on experimental colitis. Sixty 8-week-old BALB/c mice were divided into six groups. The five groups that had received DSS were administered normal saline, mesalazine, L. fermentum CCTCC M206110 strain, L. crispatus CCTCC M206119 strain, or L. plantarum NCIMB8826 strain. We assessed the severity of colitis based on disease activity index (DAI), body weight loss, colon length, and histologic damage. RESULTS: The detection rate of four of the 11 Lactobacillus species decreased significantly (P < 0.05), and the detection rate of two of the 11 Lactobacillus species increased significantly (P < 0.05) in UC patients. Relative quantitative analysis revealed that eight Lactobacillus species declined significantly in UC patients (P < 0.05), while three Lactobacillus species increased significantly (P < 0.05). The CCTCC M206110 treatment group had less weight loss and colon length shortening, lower DAI scores, and lower histologic scores (P < 0.05), while the CCTCC M206119 treatment group had greater weight loss and colon length shortening, higher histologic scores, and more severe inflammatory infiltration (P < 0.05). NCIMB8826 improved weight loss and colon length shortening (P < 0.05) with no significant influence on DAI and histologic damage in the colitis model. CONCLUSIONS: Administration of an L. crispatus CCTCC M206119 supplement aggravated DSS-induced colitis. L. fermentum CCTCC M206110 proved to be effective at attenuating DSS-induced colitis. The potential probiotic effect of L. plantarum NCIMB8826 on UC has yet to be assessed.

Effects of different diets on intestinal microbiota and nonalcoholic fatty liver disease development.

AIM: To study the effects of different diets on intestinal microbiota and nonalcoholic fatty liver disease (NAFLD) development at the same caloric intake. METHODS: Thirty male Sprague-Dawley rats were randomized into five groups (six rats each). The control diet (CON) group and free high-fat diet (FFAT) group were allowed ad libitum access to a normal chow diet and a high-fat diet, respectively. The restrictive high-fat diet (RFAT) group, restrictive high-sugar diet (RSUG) group, and high-protein diet (PRO) group were fed a high-fat diet, a high-sugar diet, and a high-protein diet, respectively, in an isocaloric way. All rats were killed at 12 wk. Body weight, visceral fat index (visceral fat/body weight), liver index (liver/body weight), insulin resistance, portal lipopolysaccharide (LPS), serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and liver triglycerides were measured. The intestinal microbiota in the different groups of rats was sequenced using high-throughput sequencing technology. RESULTS: The FFAT group had higher body weight, visceral fat index, liver index, peripheral insulin resistance, portal LPS, serum ALT, serum AST, and liver triglycerides compared with all other groups (P < 0.05). Taking the same calories, the RFAT and RSUG groups demonstrated increased body weight, visceral fat index, peripheral insulin resistance and liver triglycerides compared with the PRO group (P < 0.05). The RFAT group also showed increased portal LPS compared with the PRO group (P < 0.05). Unweighted UniFrac principal coordinates analysis of the sequencing data revealed that the intestinal microbiota structures of the CON, FFAT, RSUG and PRO groups were roughly separated away from each other. Taxon-based analysis showed that, compared with the CON group, the FFAT group had an increased abundance of Firmicutes, Roseburia and Oscillospira bacteria, a higher ratio of Firmicutes to Bacteroidetes, and a decreased abundance of Bacteroidetes, Bacteroides and Parabacteroides bacteria (P < 0.05). The RFAT group showed an increased abundance of Firmicutes and decreased abundance of Parabacteroides bacteria (P < 0.05). The RSUG group showed an increased abundance of Bacteroidetes and Sutterella bacteria, higher ratio of Bacteroidetes to Firmicutes, and a decreased abundance of Firmicutes (P < 0.05). The PRO group showed an increased abundance of Bacteroidetes, Prevotella, Oscillospira and Sutterella bacteria, and a decreased abundance of Firmicutes (P < 0.05). Compared with the FFAT group, the RFAT group had an increased abundance of Bacteroidetes, higher ratio of Bacteroidetes to Firmicutes, and decreased abundance of Firmicutes and Oscillospira bacteria (P < 0.05). CONCLUSION: Compared with the high-protein diet, the NAFLD-inducing effects of high-fat and high-sugar diets are independent from calories, and may be associated with changed intestinal microbiota.

Glycoprotein screening in colorectal cancer based on differentially expressed Tn antigen.

Colorectal cancer (CRC) is one of the most common cancers worldwide, and the identification of new biomarkers for CRC is valuable for its diagnosis and treatment. We aimed to screen differentially expressed glycoproteins (especially O-glycoproteins) and to identify diagnostic or therapeutic candidates for colorectal cancer (CRC) based on different Tn antigen expression levels. Fresh cancer tissues and adjacent healthy tissues were obtained from CRC patients and classified into three groups based on their Tn antigen expression: CRC with negative Tn expression (CRC Tn­), CRC with positive Tn expression (CRC Tn+) and normal control without Tn expression (NC). Protein extractions were separated and identified by iTRAQ technology. Glycoproteins and O-glycoproteins were selected using UniProt and DAVID. Deep bioinformatic analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KO), was used to annotate this O-glycoprotein interaction network. Subsequently, two O­glycoproteins were verified by western blotting and immunohistochemistry in either LS174T cells or CRC tissues. We found that 330 differentially expressed proteins were identified by iTRAQ between CRC Tn­ and NC tissues, 317 between CRC Tn+ and NC tissues, and 316 between CRC Tn­ and Tn+ tissues. Of the 316 proteins, 55 glycoproteins and 19 O­glycoproteins were identified and analyzed via deep informatics. Namely, different Tn antigen expression levels in CRC led to differential protein expression patterns, especially for glycoproteins and O­glycoproteins. Decorin and SORBS1, two representative functional O-glycoproteins, were significantly downregulated in the CRC Tn+ tissues compared with the level in the CRC Tn­ or NC tissues. Based on this deep bioinformatic analysis, Decorin and SORBS1 are hypothesized to be involved in the TGF­ß and PPAR­Î³ signaling pathways, respectively.