ABSTRACT
High mobility group box proterin-1 (HMGB-1) is a multifunctional protein that can be released by various programmed cell deaths (PCDs), such as necroptosis and ferroptosis. PCDs play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the role of HMGB-1 in the process of SLE remains unclear. This study aims to demonstrate the potential diagnosing role of serum HMGB-1 in SLE that released by necroptosis and ferroptosis. We found that the serum levels of HMGB-1, receptor-interacting protein kinase 3 (RIPK3) /mixed lineage kinase domain-like protein (MLKL) related with necroptosis, and metabolites associated with ferroptosis were significantly upregulated in SLE patients compared to HC individuals. These serum levels were positively correlated with SLE disease activity. Additionally, the serum level of HMGB-1 showed a strong positive correlated with the levels of RIPK3/MLKL and ferroptosis metabolites. Moreover, the serum level of HMGB-1 was correlated with renal involvement and high-antinuclear antibodies (ANA) titer. After SLE serum and interferon γ (IFN-γ) treatment in vitro, the level of necroptosis and ferroptosis markers were activated and HMGB1 was released both in HEK293 and HK2 cells. Clinically, HMGB-1 was considered as a significant independent risk factor in SLE serum by binary logistic assay. Notably, HMGB-1 exhibited outstanding diagnostic ability for SLE by the area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. Taken together, our study indicates that the serum level of HMGB-1 is a promising biomarker for the diagnosis and monitoring of SLE.
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BACKGROUND: The study aimed to analyze the characteristic clinical manifestations of patients with intestinal disease Meckel's diverticulum (MD) complicated by digestive tract hemorrhage. Moreover, we aimed to evaluate the value of double-balloon enteroscopy (DBE) in MD diagnosis and the prognosis after laparoscopic diverticula resection. AIM: To evaluate the value of DBE in the diagnosis and the prognosis after laparoscopic diverticula resection for MD with bleeding. METHODS: The study retrospectively analyzed relevant data from 84 MD patients treated between January 2015 and March 2022 and recorded their clinical manifestations, auxiliary examination, and follow-up after laparoscopic resection of diverticula. RESULTS: (1) Among 84 MD patients complicated with hemorrhage, 77 were male, and 7 were female with an average age of 31.31 ± 10.75 years. The incidence was higher in men than in women of different ages; (2) Among the 84 MD patients, 65 (78.40%) had defecated dark red stools, and 50 (58.80%) had no accompanying symptoms during bleeding, indicating that most MD bleeding appeared a dark red stool without accompanying symptoms; (3) The shock index of 71 patients (85.20%) was < 1, suggesting that the blood loss of most MD patients was less than 20%-30%, and only a few patients had a blood loss of > 30%; (4) The DBE-positive rate was 100% (54/54), 99mTc-pertechnetate-positive scanning rate was 78% (35/45) compared with capsule endoscopy (36%) and small intestine computed tomography (19%). These results suggest that DBE and 99mTc-pertechnetate scans had significant advantages in diagnosing MD and bleeding, especially DBE was a highly precise examination method in MD diagnosis; (5) A total of 54 MD patients with hemorrhage underwent DBE examination before surgery. DBE endoscopy revealed many mucosal manifestations including normal appearance, inflammatory changes, ulcerative changes, diverticulum inversion, and nodular hyperplasia, with ulcerative changes being the most common (53.70%). This suggests that diverticular mucosal ulcer was the main cause of MD and bleeding; and (6) Laparoscopic dissection of diverticulae was performed in 76 patients, The patients who underwent postoperative follow-up did not experience any further bleeding. Additionally, follow-up examination of the 8 cases who had declined surgery revealed that 3 of them experienced a recurrence of digestive tract bleeding. These findings indicate that laparoscopic diverticula resection in MD patients complicated by bleeding had a favorable prognosis. CONCLUSION: Bleeding associated with MD was predominantly observed in male adolescents, particularly at a young age. DBE was a highly precise examination method in MD diagnosis. Laparoscopic diverticula resection effectively prevented MD bleeding and had a good prognosis.
ABSTRACT
Due to its unclear etiology, there is no specific medicine to cure the recurrent and incurable inflammatory bowel disease (IBD). Unhealthy dietary habits unconsciously contributed to the progression of IBD, for example a High-Salt-Diet (HSD) is the most neglected and frequently adopted habit. However, the molecular mechanism of how HSD aggravates the progression of IBD has yet to remain uncovered. Herein, we focus on the hypothesis that necroptosis pathway may be involved in the process of IBD exacerbated by HSD. To this end, different gene expression (DEGs) profiles of human epithelia under hypertonic culture conditions were applied to screen candidate pathways. What's more, gene expression manipulation, immune microenvironment detection, RIPK3/MLKL gene knockout (KO), and wild-type (WT) mice were carried out to research the promotion of IBD progression under treatments of high salt intake. Based on our present results, gene expression profiles in human normal colon epithelia cell NCM460 were significantly changed under salt- or sucrose-induced hypertonic culture conditions. RIPK3 was significantly up-regulated under both conditions. Furthermore, mice colon epithelia cell CT26 growth was inhibited in a time- and dose-dependent manner by extra NaCl incubation. Autophagy, and Necroptosis pathways were activated and enhanced by LPS pretreatment. HSD significantly exacerbated DSS-induced IBD symptoms in vivo in a dose-dependent manner. Moreover, RIPK3-/- and MLKL-/- mice presented severe IBD symptoms in vivo. Overall, the results demonstrated that HSD aggravated the IBD progression via necroptosis activation, providing novel strategies and promising targets for the clinical treatment of IBD.
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Background: Epithelial-mesenchymal transition (EMT) is closely associated with cancer cell metastasis. Colon adenocarcinoma (COAD) is one of the most common malignancies in the world, and its metastasis leading to poor prognosis remains a challenge for clinicians. The purpose of this study was to explore the prognostic value of EMT-related genes (EMTRGs) by bioinformatics analysis and to develop a new EMTRGs prognostic signature for COAD. Methods: The TCGA-COAD dataset was downloaded from the TCGA portal as the training cohort, and the GSE17538 and GSE29621 datasets were obtained from the GEO database as the validation cohort. The best EMTRGs prognostic signature was constructed by differential expression analysis, Cox, and LASSO regression analysis. Gene set enrichment analysis (GSEA) is used to reveal pathways that are enriched in high-risk and low-risk groups. Differences in tumor immune cell levels were analyzed using microenvironmental cell population counter and single sample gene set enrichment analysis. Subclass mapping analysis and Genomics of Drug Sensitivity in Cancer were applied for prediction of immunotherapy response and chemotherapy response, respectively. Results: A total of 77 differentially expressed EMTRGs were identified in the TCGA-COAD cohort, and they were significantly associated with functions and pathways related to cancer cell metastasis, proliferation, and apoptosis. We constructed EMTRGs prognostic signature with COMP, MYL9, PCOLCE2, SCG2, and TIMP1 as new COAD prognostic biomarkers. The high-risk group had a poorer prognosis with enhanced immune cell infiltration. The GSEA demonstrated that the high-risk group was involved in "ECM Receptor Interaction," "WNT Signaling Pathway" and "Colorectal Cancer." Furthermore, patients with high risk scores may respond to anti-CTLA4 therapy and may be more resistant to targeted therapy agents BI 2536 and ABT-888. Conclusion: Together, we developed a new EMTRGs prognostic signature that can be an independent prognostic factor for COAD. This study has guiding implications for individualized counseling and treatment of COAD patients.
Subject(s)
Adenocarcinoma , Colonic Neoplasms , Humans , Epithelial-Mesenchymal Transition , Prognosis , ApoptosisABSTRACT
Sesamum indicum is a major and important oilseed crop that is believed to promote human health in many countries, especially in China. Sesame seeds contain two types of lignans: lipid-soluble lignans and water-soluble glucosylated lignans. The major glucosylated lignans are sesaminol glucosides (SGs). So far, four sesaminol isomers and four SGs are identified. During the naturally occurring process of SGs production, sesaminol is generated first from two molecules of E-coniferyl alcohol, and then the sugar is added to the sesaminol one by one, leading to production of SGs. Sesaminol can be prepared from SGs, from sesamolin, and through artificial synthesis. SGs are metabolized in the liver and intestine and are then transported to other tissues. They exhibit several biological activities, most of which are based on their antioxidant and anti-inflammatory activities. In this paper, we present an overview of the current status of research on sesaminol and SGs. We have also discussed their synthesis, preparation, metabolism, and biological activities. It has been suggested that sesaminol and SGs are important biological substances with strong antioxidant properties in vitro and in vivo and are widely used in the food industry, medicine, and cosmetic products. The recovery and utilization of SGs from sesame seed cake after oil processing will generate massive economic benefits.
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BACKGROUND: Heterotopic tumor is a rare disease. Thus far, no cases of heterotopic cholangiocarcinoma have been reported in the world. Cholangiocarcinoma mainly metastasizes by direct invasion, and it can lead to liver metastasis in its advanced stage. There were few clinical cases of gastric metastasis in advanced tumors, mainly seen in breast cancer, lung cancer, liver cancer, malignant melanoma, choriocarcinoma, and hematological tumors. Metastases of cholangiocarcinoma to the stomach also are exceptionally rare. CASE PRESENTATION: A 58-year-old man was admitted to the hospital because of difficulty swallowing for one year. Upon gastroscopy, we found the tumor at the region of the cardia and gastric fundus. Macroscopical appearance of the tumor suggested its malignant nature. Computed tomography (CT) findings showed that the wall of the cardia, fundus, and stomach body were thickened, suggesting a tumor. Because the patient had obvious difficulty swallowing, we invited cardiothoracic surgeons for consultation. They considered that the patient had definite mechanical obstruction in the lower esophagus; hence, they performed an operation. Immunohistochemical staining revealed low-to-medium differentiated adenocarcinoma (containing mucinous adenocarcinoma components) of biliary origin. CONCLUSIONS: We highlight the importance of the endoscopic biopsy of gastric tumor. However, when its results are inconsistent with the clinician's judgment, further examination is required. Endoscopic ultrasonography and enhanced CT may be a good choice. If necessary, on the premise of patient acceptance, the diagnosis could be confirmed after surgical excision. Here we report a case of a patient with heterotopic cholangiocarcinoma in the gastric fundus. The most common tissue ectopias in the digestive tract include esophagogastric gastric mucosal ectopia, duodenal gastric mucosal ectopia, and gastric mucosal small intestinal ectopia. Thus far, there have been no reports of ectopic cholangiocarcinoma and associated cancer in the stomach. In addition, metastases of cholangiocarcinoma to the stomach are also exceptionally rare, and most of them are due to a direct invasion. The discovery of the primary lesion is an important clue for the reliable diagnosis in such cases.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Deglutition Disorders , Gastritis , Stomach Neoplasms , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/pathology , Cardia/pathology , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/pathology , Diagnostic Errors , Gastritis/pathology , Humans , Male , Middle Aged , Stomach Neoplasms/pathologyABSTRACT
Spermine, spermidine and putrescine polyamines are naturally occurring ubiquitous positively charged amines and are essential metabolites for biological functions in our life. These compounds play a crucial role in many cell processes, including cellular proliferation, growth, and differentiation. Intracellular levels of polyamines depend on their biosynthesis, transport and degradation. Polyamine levels are high in cancer cells, which leads to the promotion of tumor growth, invasion and metastasis. Targeting polyamine metabolism as an anticancer strategy is considerably rational. Due to compensatory mechanisms, a single strategy does not achieve satisfactory clinical effects when using a single agent. Combination regimens are more clinically promising for cancer chemoprevention because they work synergistically with causing little or no adverse effects due to each individual agent being used at lower doses. Moreover, bioactive substances have advantages over single chemical agents because they can affect multiple targets. In this review, we discuss anticancer strategies targeting polyamine metabolism and describe how combination treatments and effective natural active ingredients are promising therapies. The existing research suggests that polyamine metabolic enzymes are important therapeutic targets and that combination therapies can be more effective than monotherapies based on polyamine depletion.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Homeostasis/drug effects , Neoplasms/drug therapy , Neoplasms/metabolism , Polyamines/antagonists & inhibitors , Polyamines/metabolism , Animals , Biological Products/pharmacology , Biological Products/therapeutic use , Humans , Polyamines/chemistryABSTRACT
HIV infection induces pathological changes in the intestinal mucosa. Here, a successful endoscopy was performed on the colon of a Chinese rhesus macaque by using Olympus CV170 gastroscope. The stability on postoperative recovery and the integrity of biopsy tissue implied a possibility of achieving AIDS longitudinal intestinal research on macaques.
Subject(s)
Acquired Immunodeficiency Syndrome/pathology , Colonoscopy/veterinary , Intestinal Mucosa/diagnostic imaging , Macaca mulatta , Animals , Simian Acquired Immunodeficiency Syndrome/pathologyABSTRACT
BACKGROUND: Although contact force (CF)sensing catheters improve procedural effectiveness and safety of atrial fibrillation ablation, recent reports documented a higher incidence of atrioesophageal fistula formation relative to ablation with nonCF-sensing catheters.The present study was to assess whether restricting CF to <20 g reduced risk for esophageal injury (EI) in patients with atrial fibrillation undergoing circumferential pulmonary vein isolation. METHODS: This prospective, single-center, randomized study enrolled 89 consecutive patients (mean age, 57.2±11.3 years; 57.3% men) with atrial fibrillation (68.5% paroxysmal and 31.5% persistent). Computed tomography angiography, transesophageal echocardiography, and esophageal endoscopy were conducted before the procedure, and a repeat esophageal endoscopy was performed after the procedure. Patients were randomized to restricted-CF group (n=44) or non-CF group (n=45), with circumferential pulmonary vein isolation using a CF-sensing (CF restricted to <20 g) or nonCF-sensing catheter, respectively. The primary end point was rate of EI post ablation. RESULTS: Baseline characteristics were evenly distributed between groups, without a case of preprocedural EI. With the same power setting, similar ablation time and average measured catheter tip temperature during posterior wall ablation just opposite to the esophagus in all patients in the restricted-CF group versus non-CF groups, there were no cases versus 9 (20%) cases of EI post ablation, respectively, with similar rate of freedom from atrial tachyarrhythmias at mean 31.3±6.5 months follow-up (68.2% versus 64.4%; P=0.3798). CONCLUSIONS: Risk for EI was minimized when CF was restricted to <20 g at the posterior left atrial wall, where the circumferential pulmonary vein isolation lesion set and the course of the esophagus overlapped in all subjects.
Subject(s)
Atrial Fibrillation/surgery , Cardiac Catheterization/methods , Catheter Ablation/methods , Heart Atria/diagnostic imaging , Heart Conduction System/physiopathology , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Atrial Function, Left/physiology , Body Surface Potential Mapping/methods , Computed Tomography Angiography , Echocardiography, Transesophageal , Female , Follow-Up Studies , Heart Atria/physiopathology , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Prospective Studies , Pulmonary Veins/growth & development , Pulmonary Veins/surgery , Treatment OutcomeABSTRACT
Minimal hepatic encephalopathy (MHE) is caused by dysbiosis of gut microbiota, particularly the ammonia-producing bacteria. Given the efficacy of certain treatments on MHE and the connection between alcoholism and MHE, a thorough understanding of how these strategies affect the gut microbiota in patients (alcoholic or non-alcoholic) will facilitate the assessment of their efficacy in the reshaping of gut microbiota. In the present study, a metagenomics approach was adopted to reveal alterations in gut microbiota of 14 MHE patients following treatment with rifaximin alone or rifaximin plus probiotics. Patients were grouped into the alcoholic and non-alcoholic groups to examine differences in terms of their response to treatment. Treatment reduced the overall microbiota diversity and decreased the abundance of certain ammonia-producing bacteria, such as Clostridium, with the treatment of rifaximin plus probiotics presenting a more apparent effect. Non-alcoholic MHE patients responded better to the treatment, as they presented greater reduction in microbiota diversity and a more consistent decline in certain ammonia-producing bacteria genera (such as Clostridium and Streptococcus) belonging to the Firmicutes phylum. In conclusion, treatment with rifaximin alone and rifaximin plus probiotics exhibited a different effect in different MHE patients, decreasing the overall gut microbiota diversity to various extents and reshaping microbiota in different ways. Furthermore, non-alcoholic MHE patients responded better to treatment in microbiota alterations.