Potential shared pathogenic mechanisms between endometriosis and inflammatory bowel disease indicate a strong initial effect of immune factors.

Introduction: Over the past decades, immune dysregulation has been consistently demonstrated being common charactoristics of endometriosis (EM) and Inflammatory Bowel Disease (IBD) in numerous studies. However, the underlying pathological mechanisms remain unknown. In this study, bioinformatics techniques were used to screen large-scale gene expression data for plausible correlations at the molecular level in order to identify common pathogenic pathways between EM and IBD. Methods: Based on the EM transcriptomic datasets GSE7305 and GSE23339, as well as the IBD transcriptomic datasets GSE87466 and GSE126124, differential gene analysis was performed using the limma package in the R environment. Co-expressed differentially expressed genes were identified, and a protein-protein interaction (PPI) network for the differentially expressed genes was constructed using the 11.5 version of the STRING database. The MCODE tool in Cytoscape facilitated filtering out protein interaction subnetworks. Key genes in the PPI network were identified through two topological analysis algorithms (MCC and Degree) from the CytoHubba plugin. Upset was used for visualization of these key genes. The diagnostic value of gene expression levels for these key genes was assessed using the Receiver Operating Characteristic (ROC) curve and Area Under the Curve (AUC) The CIBERSORT algorithm determined the infiltration status of 22 immune cell subtypes, exploring differences between EM and IBD patients in both control and disease groups. Finally, different gene expression trends shared by EM and IBD were input into CMap to identify small molecule compounds with potential therapeutic effects. Results: 113 differentially expressed genes (DEGs) that were co-expressed in EM and IBD have been identified, comprising 28 down-regulated genes and 86 up-regulated genes. The co-expression differential gene of EM and IBD in the functional enrichment analyses focused on immune response activation, circulating immunoglobulin-mediated humoral immune response and humoral immune response. Five hub genes (SERPING1、VCAM1、CLU、C3、CD55) were identified through the Protein-protein Interaction network and MCODE.High Area Under the Curve (AUC) values of Receiver Operating Characteristic (ROC) curves for 5hub genes indicate the predictive ability for disease occurrence.These hub genes could be used as potential biomarkers for the development of EM and IBD. Furthermore, the CMap database identified a total of 9 small molecule compounds (TTNPB、CAY-10577、PD-0325901 etc.) targeting therapeutic genes for EM and IBD. Discussion: Our research revealed common pathogenic mechanisms between EM and IBD, particularly emphasizing immune regulation and cell signalling, indicating the significance of immune factors in the occurence and progression of both diseases. By elucidating shared mechanisms, our study provides novel avenues for the prevention and treatment of EM and IBD.

Elucidating the molecular basis of ATP-induced cell death in breast cancer: Construction of a robust prognostic model.

BACKGROUND: Breast cancer is a multifaceted and formidable disease with profound public health implications. Cell demise mechanisms play a pivotal role in breast cancer pathogenesis, with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence. AIM: To investigate the impact of ATP-induced cell death (AICD) on breast cancer, enhancing our understanding of its mechanism. METHODS: The foundational genes orchestrating AICD mechanisms were extracted from the literature, underpinning the establishment of a prognostic model. Simultaneously, a microRNA (miRNA) prognostic model was constructed that mirrored the gene-based prognostic model. Distinctions between high- and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized, with the aim of delineating common influence mechanisms, substantiated through enrichment analysis and immune infiltration assessment. RESULTS: The mRNA prognostic model in this study encompassed four specific mRNAs: P2X purinoceptor 4, pannexin 1, caspase 7, and cyclin 2. The miRNA prognostic model integrated four pivotal miRNAs: hsa-miR-615-3p, hsa-miR-519b-3p, hsa-miR-342-3p, and hsa-miR-324-3p. B cells, CD4+ T cells, CD8+ T cells, endothelial cells, and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways, while miRNA risk scores significantly enriched 29 signaling pathways, with 16 pathways being jointly enriched. CONCLUSION: Of paramount significance, distinct mRNA and miRNA signature models were devised tailored to AICD, both potentially autonomous prognostic factors. This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools, offering an unparalleled window for innovative interventions. Essentially, this paper reveals the hitherto enigmatic link between AICD and breast cancer, potentially leading to revolutionary progress in personalized oncology.

Endovascular treatment of systematic isolated mesenteric artery dissection with a patent false lumen: Bare stents alone versus stent-assisted coiling.

OBJECTIVES: Bare stent treatment and bare stent-assisted coiling treatment have not been directly compared in symptomatic isolated superior mesenteric artery dissection with a patent false lumen. Thus, we compared the early and mid-term outcomes of bare stent treatment and bare stent-assisted coiling treatment to determine the most effective remedy for patients with this condition. METHODS: Consecutive patients diagnosed with systematic isolated superior mesenteric artery dissection with a patent false lumen admitted to the study hospital between January 2016 and December 2021 were enrolled in this retrospective study. Their demographic data, clinical findings, treatment options, early outcomes, and follow-up results were analyzed. RESULTS: A total of 85 patients (83 men) were included. 34.1% (n = 29) adopted bare stent treatment and 65.9% (n = 56) underwent bare stent-assisted coiling treatment. The symptoms were relieved in all patients (100%) with bare stent treatment and bare stent-assisted coiling treatment. There was no significant difference in the length of hospital stay between the two endovascular treatments (p = 0.354). The cumulative complete remodeling rate was 100% in bare stent-assisted coiling treatment vs. 70.4% in bare stent treatment (p < 0.0001). The prevalence of adverse events for abdominal pain recurrence (none in BST or bare stent-assisted coiling treatment), and formation of the aneurysm (two in bare stent treatment, and none in bare stent-assisted coiling treatment) showed no significant difference at follow-up. CONCLUSION: Both bare stent treatment and bare stent-assisted coiling treatment for symptomatic isolated superior mesenteric artery dissection with a patent false lumen have the same satisfying early outcome. In the midterm follow-up, bare stent-assisted coiling treatment has the higher cumulative complete remodeling rate which could be prioritized to treat this condition.

Machine learning-based integrated identification of predictive combined diagnostic biomarkers for endometriosis.

Background: Endometriosis (EM) is a common gynecological condition in women of reproductive age, with diverse causes and a not yet fully understood pathogenesis. Traditional diagnostics rely on single diagnostic biomarkers and does not integrate a variety of different biomarkers. This study introduces multiple machine learning techniques, enhancing the accuracy of predictive models. A novel diagnostic approach that combines various biomarkers provides a new clinical perspective for improving the diagnostic efficiency of endometriosis, holding significant potential for clinical application. Methods: In this study, GSE51981 was used as a test set, and 11 machine learning algorithms (Lasso, Stepglm, glmBoost, Support Vector Machine, Ridge, Enet, plsRglm, Random Forest, LDA, XGBoost, and NaiveBayes) were employed to construct 113 predictive models for endometriosis. The optimal model was determined based on the AUC values derived from various algorithms. These genes were then evaluated using nine machine learning algorithms (Random Forest, SVM, Gradient Boosting Machine, LASSO, XGB, NNET, Generalized Linear Model, KNN, and Decision Tree) to assess significance scores and identify diagnostic genes for each algorithm. The diagnostic value of these genes was further validated in external datasets from GSE7305, GSE11691, and GSE120103. Results: Analysis of the GSE51981 dataset revealed 62 DEGs. The Stepglm [Both] and plsRglm algorithms identified 30 genes with the most potential using the AUC evaluation. Subsequently, nine machine learning algorithms were applied to select diagnostic genes, leading to the identification of five key diagnostic genes using the LASSO algorithm. The ADAT1 gene exhibited the best single-gene predictive performance, with an AUC of 0.785. A combination of genes (FOS, EPHX1, DLGAP5, PCSK5, and ADAT1) achieves an AUC of 0.836 in the test dataset. Moreover, these genes consistently exhibited an AUC exceeding 0.78 in all validation datasets, demonstrating superior predictive performance. Furthermore, correlation analysis with immune infiltration strengthened their predictive value by demonstrating the close relationship of the diagnostic genes with immune infiltrating cells. Conclusion: A combination of biomarkers consisting of FOS, EPHX1, DLGAP5, PCSK5, and ADAT1 can serve as a diagnostic tool for endometriosis, enhancing diagnostic efficiency. The association of these genes with immune infiltrating cells reveals their potential role in the pathogenesis of endometriosis, providing new insights for early detection and treatment.

Physical and mental health impairments experienced by operating surgeons and camera-holder assistants during laparoscopic surgery: a cross-sectional survey.

Introduction: Surgeons may experience physical and mental health problems because of their jobs, which may lead to chronic muscle damage, burnout, or even withdrawal. However, these are often ignored in camera-holder assistants during laparoscopic surgery. We aimed to analyze the differences between operating surgeons and camera-holder assistants. Methods: From January 1, 2022, to December 31, 2022, a cross-sectional survey was conducted to evaluate the muscle pain, fatigue, verbal scolding, and task load for operating surgeons and camera-holder assistants. The Nordic Musculoskeletal Questionnaire, the Space Administration Task Load Index, and the Surgical Task Load Index (SURG-TLX) were combined in the questionnaire. Results: 2,184 operations were performed by a total of 94 operating surgeons and 220 camera assistants. 81% of operating surgeons and 78% of camera-holder assistants reported muscle pain/discomfort during the procedure. The most affected anatomic region was the shoulders for operating surgeons, and the lower back for camera-holder assistants. Intraoperative fatigue was reported by 41.7% of operating surgeons and 51.7% of camera-holder assistants. 55.2% of camera-holder assistants reported verbal scolding from the operating surgeons, primarily attributed to lapses in laparoscope movement coordination. The SURG-TLX results showed that the distributions of mental, physical, and situational stress for operating surgeons and camera-holder assistants were comparable. Conclusion: Like operating surgeons, camera-holder assistants also face similar physical and mental health impairments while performing laparoscopic surgery. Improvements to the working conditions of the camera-holder assistant should not be overlooked.

The alleviating effect and mechanism of GLP-1 on ulcerative colitis.

Ulcerative Colitis (UC) is a major type of chronic inflammatory bowel disease of the colonic mucosa and exhibits progressive morbidity. The incidence and prevalence of UC is increasing worldwide. The global burden of UC, which can substantially reduce quality of life, is clearly increasing. These data highlight the need for research into prevention of UC and innovations in health-care systems to manage this complex and costly disease. Glucagon-like peptide-1 (GLP-1), a new antidiabetic drug, is used to treat Type 2 Diabetes Mellitus (T2DM). Accumulating evidence suggests that GLP-1 has additional roles other than glucose-lowering effects. Despite the abundance of GLP-1 research, studies in UC have been less consistent, especially body weight; for example, body weight, colon length, colon injury score, intestinal microbiota, remain to be studied further. To date, the molecular mechanism of the protective effect of GLP-1 on UC remains obscure. The effect of GLP-1 was studied by using a dextran sulfate sodium (DSS)-induced colitic mice and lipopolysaccharide (LPS) treated RAW264.7 cells (macrophage cell line) under in vivo and in vitro conditions, respectively. Our results indicate that GLP-1 significantly relieves ulcerative colitis as it represses the production of proinflammatory mediators. In addition, GLP-1 blocks the activation of the protein kinase B (AKT)/nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways. GLP-1 also alleviates DSS-induced injury to the intestinal mucosa and dysbiosis of gut microbiota. Altogether, GLP-1 has protection effect on ulcerative colitis. Thus, GLP-1 can be considered as a potential therapeutic candidate for the treatment of UC.

Midterm Results of the Conservative, Bare Stent, and Bare Stent-Assisted Coiling Treatments for Symptomatic Isolated Superior Mesenteric Artery Dissection.

BACKGROUND: We compared the early and midterm (31, 3-63 months) outcomes of conservative treatment, bare stent treatment (BST), and bare stent-assisted coiling treatment (BSACT) to determine the most effective treatment for patients with symptomatic isolated superior mesenteric artery dissection (SISMAD). METHODS: Consecutive patients with SISMAD admitted to the study hospital between January 2016 and December 2021 were included in this retrospective study. Their demographic data, clinical findings, treatment options, early outcomes, and follow-up results were analyzed. RESULTS: A total of 121 patients were included in the study (23 with conservative treatment, 42 with BST, and 56 with BSACT). Symptoms were relieved in 91.3% of conservative patients, whereas all patients (100%) with BST or BSACT had symptom relief (P = 0.035). There was no significant difference in the length of hospital stay between the 2 endovascular treatments (P = 0.9051), but hospital stay was significantly shorter compared to conservative treatment (P < 0.0001). The cumulative rate of complete remodeling was 100% for BSACT versus 46.3% for BST (P < 0.0001) versus 42.9% for conservative patients (P < 0.0001). There were no significant differences between the last 2 groups (P = 0.3925). The prevalence of adverse events for abdominal pain recurrence and aneurysm formation was also significantly lower in the BSACT group at follow-up. CONCLUSIONS: BSACT for SISMAD has a preferable early outcome. The cumulative complete remodeling rate and the event-free survival rate are satisfactory at midterm follow-up. BSACT is an effective approach for SISMAD.

Strategies involving low-molecular-weight heparin for the treatment and prevention of venous thromboembolism in patients with obesity: A systematic review and meta-analysis.

Introduction: Recent studies have indicated that the dosage of LMWH in patients with specific weights may be controversial. Therefore, we conducted a meta-analysis to explore an appropriate dosage of LMWH for the prevention and treatment of venous thromboembolism (VTE) in patients with obesity. Materials and methods: We searched the PubMed, EMBASE, and Cochrane Library databases up to July 23, 2022. Study selection, bias analysis, and information extraction were performed by three independent reviewers. The occurrence or recurrence of VTE and bleeding events were the primary outcomes we assessed. Results: Eleven studies (a total of 6266 patients) were included in the prevention group, and 6 studies (a total of 3225 patients) were included in the treatment group. For VTE prophylaxis, compared with the standard-dosage group, the high-dosage group had a lower incidence of VTE (OR: 0.47, 95% CI: 0.27-0.82, P=0.007) and a similar incidence of bleeding events (OR: 0.86, 95% CI: 0.69-1.08, P=0.020). For VTE therapy, compared to the standard-dosage group, the reduced-dosage group had a similar incidence of VTE recurrence (OR: 0.86, 95% CI: 0.11-6.84, P=0.89) but a lower incidence of bleeding events (OR: 0.30, 95% CI: 0.10-0.89, P=0.03). Conclusion: In patients with obesity, increasing the dosage of LMWH is a more appropriate option for the prevention of VTE. Due to the limited evidence, reducing the therapeutic dosage of LMWH requires careful consideration. Larger-scale, well-designed randomized controlled trials are necessary. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier ID=CRD42022298128.

Protamine 1 as a secreted colorectal cancer-specific antigen facilitating G1/S phase transition under nutrient stress conditions.

PURPOSE: Cancer testis antigens (CTAs) are optimal tumor diagnostic markers and involved in carcinogenesis. However, colorectal cancer (CRC) related CTAs are less reported with impressive diagnostic capability or relevance with tumor metabolism rewiring. Herein, we demonstrated CRC-related CTA, Protamine 1 (PRM1), as a promising diagnostic marker and involved in regulation of cellular growth under nutrient deficiency. METHODS: Transcriptomics of five paired CRC tissues was used to screen CRC-related CTAs. Capability of PRM1 to distinguish CRC was studied by detection of clinical samples through enzyme linked immunosorbent assay (ELISA). Cellular functions were investigated in CRC cell lines through in vivo and in vitro assays. RESULTS: By RNA-seq and detection in 824 clinical samples from two centers, PRM1 expression were upregulated in CRC tissues and patients` serum. Serum PRM1 showed impressive accuracy to diagnose CRC from healthy controls and benign gastrointestinal disease patients, particularly more sensitive for early-staged CRC. Furthermore, we reported that when cells were cultured in serum-reduced medium, PRM1 secretion was upregulated, and secreted PRM1 promoted CRC growth in culture and in mice. Additionally, G1/S phase transition of CRC cells was facilitated by PRM1 protein supplementation and overexpression via activation of PI3K/AKT/mTOR pathway in serum deficient medium. CONCLUSIONS: In general, our research presented PRM1 as a specific CRC antigen and illustrated the importance of PRM1 in CRC metabolism rewiring. The new vulnerability of CRC cells was also provided with the potential to be targeted in future. Diagnostic value and grow factor-like biofunction of PRM1 A represents the secretion process of PRM1 regulated by nutrient deficiency. B represents activation of PI3K/AKT/mTOR pathway of secreted PRM1.

ATP-induced cell death: a novel hypothesis for osteoporosis.

ATP-induced cell death has emerged as a captivating realm of inquiry with profound ramifications in the context of osteoporosis. This study unveils a paradigm-shifting hypothesis that illuminates the prospective involvement of ATP-induced cellular demise in the etiology of osteoporosis. Initially, we explicate the morphological attributes of ATP-induced cell death and delve into the intricacies of the molecular machinery and regulatory networks governing ATP homeostasis and ATP-induced cell death. Subsequently, our focus pivots towards the multifaceted interplay between ATP-induced cellular demise and pivotal cellular protagonists, such as bone marrow-derived mesenchymal stem cells, osteoblasts, and osteoclasts, accentuating their potential contributions to secondary osteoporosis phenotypes, encompassing diabetic osteoporosis, glucocorticoid-induced osteoporosis, and postmenopausal osteoporosis. Furthermore, we probe the captivating interplay between ATP-induced cellular demise and alternative modalities of cellular demise, encompassing apoptosis, autophagy, and necroptosis. Through an all-encompassing inquiry into the intricate nexus connecting ATP-induced cellular demise and osteoporosis, our primary goal is to deepen our comprehension of the underlying mechanisms propelling this malady and establish a theoretical bedrock to underpin the development of pioneering therapeutic strategies.

Adenosine triphosphate induced cell death: Mechanisms and implications in cancer biology and therapy.

Adenosine triphosphate (ATP) induced cell death (AICD) is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions. This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology. This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer. This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis, deciphering the intricate mechanisms governing AICD, elucidating its intricate involvement in cancer signaling pathways, and scrutinizing validated key genes. Moreover, the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.

Uncovering the Sweat Biofouling Components and Distributions in Electrochemical Sensors.

Interest is growing in the creation of wearable sweat sensors for continuous, low-cost, and noninvasive health diagnosis at the molecular level. The biofouling phenomenon leads to degradation of sweat sensors' performance over time, further limiting the successive monitoring of human health status. However, to date, the mechanism of sweat fouling is still unclear, with the inability to provide effective guidance on antifouling strategies. This study clarifies chemical compositions in sweat fouling and fouling distributions on the surface of sensors. Gold film electrodes were prepared on glass and poly(ethylene terephthalate) (PET) substrates and contaminated by human facial sweat (from eccrine sweat glands and apocrine sweat glands) and palm sweat (only from eccrine sweat glands). A scanning electron microscope (SEM), an optical microscope (OM), and an atomic force microscope (AFM) were employed to study the surface morphology of biofouling electrodes. The existence of sweat fouling was characterized by AFM adhesion force, a Fourier transform infrared spectrometer (FTIR), and X-ray photoelectron spectra (XPS). FTIR along with XPS was adopted to analyze the biofouling components, and differential reflectance spectroscopy (DRS) was undertaken to observe the distribution of biofouling on the surface of the electrodes. As a result, we found that neither skin cell pieces nor recognized protein adsorption is the dominant source of biofouling, but the lipids in sweat form an inhomogeneous fouling layer on the electrode surface to reduce the electrochemical reactivity of sensors. This study provides deeper insights into sweat biofouling components and distributions and points out the right direction for resolving the problem of limited continuity in wearable sweat sensors.

Endothelial progenitor cells overexpressing platelet derived growth factor-D facilitate deep vein thrombosis resolution.

To assess the therapeutic efficacy of PDGF-D-overexpressing endothelial progenitor cells (EPCs) in deep vein thrombosis. Inferior vena cava thrombosis was induced in female Sprague Dawley (SD) rats. Animals were injected via the distal vena cava with EPCs overexpressing PDGF-D after transfection with a lentiviral vector containing the PDGF-D gene. The effect on thrombosis in animals who received EPCs was evaluated using MSB staining, immunohistochemistry, immunofluorescence, and venography; the steady-state mRNA and protein levels of PDGF-D and its receptor (PDGF-Rß) were determined by RT-PCR and Western blotting, respectively; and the PDGF-D-induced mobilization of circulating EPCs was estimated by flow cytology. Compared with controls, injection of EPCs overexpressing PDGF-D was associated with increased thrombosis resolution; recanalization; PDGF-D and PDGF-Rß expression; induction of monocyte homing; and mobilization of EPCs to the venous circulation. In a rat model, transplantation of PDGF-D-overexpressing EPCs facilitated the resolution of deep vein thrombosis.

Outcomes of Covered Stents With Vacuum Sealing Drainage For Treatment of Infected Femoral Pseudoaneurysms in Intravenous Drug Addicts.

OBJECTIVE: For treatment of infected femoral artery pseudoaneurysms (IFAPs) with the covered stent, debridement technique is important but frequently ignored. Our study aims to review our experience and outcomes of patients undergoing covered stents placement and debridement with vacuum sealing drainage (VSD). METHODS: This study retrospectively analyzed 41 intravenous drug addicts with IFAP who received covered stent implantation and debridement with VSD from January 2015 to December 2020. The diagnosis was based on the previous history of local injection and the presence of pulsatile mass at the injection site. All cases were confirmed by CT angiography (CTA), ultrasound, or digital subtraction angiography (DSA). Technical success, time of wound care, and clinical outcomes were evaluated. RESULTS: Technical success was achieved in all patients. The interval from diagnosis to treatment was 26 ± 11 hours. The time of continuous drainage with VSD was 18.79 ± 6.56 days. 38 patients (92.68%) with fresh granulation tissue were sutured and discharged from the hospital. Stents in 31(91.18%) of 34 cases were patent during follow-ups. Three patients had stent occlusion caused by thrombosis, and two of them were complicated with stent infection. The two infectious stents were removed and the femoral arteries were ligated. One of them received open-surgical reconstruction with the great saphenous because of claudication. Two patients were admitted to the hospital for rebleeding caused by drug abuse relapse. CONCLUSIONS: Covered stents placement is convenient and rapid to control massive hemorrhage in IFAPs of intravenous drug abuse. Early debridement of infected tissue with continued VSD may shorten the time of wound care and make the incidence of stent infection relatively low. Meanwhile, the patency in a short time follow-up is acceptable. These results indicate that covered stents implantation with VSD may be a safe, effective, and feasible measure for the treatment of IFAPs.

The alleviating effect and mechanism of Bilobalide on ulcerative colitis.

Dysfunction of the intestinal epithelial barrier and intestinal microbiota dysbiosis can drive the onset or aggravation of ulcerative colitis (UC). Bilobalide (BI) is an extract of Ginkgo biloba that has been shown to exhibit a range of anti-inflammatory properties. Herein, we explored functional and mechanistic effects of BI treatment in a rodent model of DSS-induced UC. These analyses revealed that BI treatment was sufficient to reduce disease severity, increase colon length, and normalize colon histological characteristics relative to those observed in DSS-treated model mice. BI also enhanced the expression of tight junction proteins associated with intestinal barrier integrity including ZO-1, Occludin, and Claudin-3. Through 16S rDNA sequencing analyses, BI was also found to influence the overall richness of the intestinal microbiome, promoting the proliferation of probiotic species including Lactobacillus. Consistent with these in vivo findings, BI treatment protected RAW264.7 cells against lipopolysaccharide (LPS)-induced inflammatory damage, suppressing the activation of the AKT/NF-κB p65 and MAPK signaling pathways in this experimental context. In summary, these findings revealed that BI can suppress MAPK and AKT/NF-κB p65 signaling, thereby suppressing the production of inflammatory cytokines including IL-1ß, IL-6, and TNF-α, while additionally alleviating UC severity by facilitating repair of the intestinal epithelial barrier and the remodeling of intestinal microbial communities.

Laparoscopic Transabdominal Preperitoneal Approach with Negative Pressure Drainage for Giant Inguinal Hernia.

Background: Giant inguinal hernia (GIH) is a rare disease but it can cause serious complications, such as intestinal obstruction and strangulation. Few studies have explored surgical treatment with respect to the transabdominal preperitoneal (TAPP) approach or measures to reduce the occurrence of postoperative seroma. Purpose: To investigate the safety and efficacy of the TAPP approach with negative pressure drainage in GIHs. Methods: From January 2017 to December 2019, 32 patients who underwent TAPP procedures with negative pressure drainage for GIHs at our hospital were reviewed. Demographic information, surgical characteristics, and follow-up data were obtained. Results: The mean age of the patients was 66, and more than half of them had medical comorbidities. All GIHs were defined as Type 1 and were successfully repaired through the TAPP approach with negative pressure drainage. The mean operative time was 146 minutes (range 122-251). After surgery, the mean drainage time was 7 days (range 5-10 days), and the mean volume of drainage in each patient was 820 mL (range 655-1020 mL). Complications occurred in 3 cases. For 1 case, the inferior epigastric artery was injured during surgery. A seroma was observed in 1 patient, which occurred 2 days after removal of the drainage tube. Finally, 1 patient developed an umbilical puncture site infection, and the wound healed after changing the dressing. The mean follow-up was 13 months (range 1-32), and there was no recurrence or mesh infection during that time. Conclusion: TAPP is a safe and effective approach for treating Type 1 GIHs with low operative complications. Negative pressure drainage through the scrotum to the preperitoneal space may reduce the incidence of seroma. Recurrence of hernias was not observed, and chronic pain seldom occurred during the follow-up period in our study.

Lnc HAGLR Promotes Colon Cancer Progression Through Sponging miR-185-5p and Activating CDK4 and CDK6 in vitro and in vivo.

BACKGROUND/AIM: LncRNA plays a key role in tumor progression. HAGLR functions as an oncogene in many cancers. However, the molecular mechanism of HAGLR in colon cancer is still unclear. METHODS: qRT-PCR was used to measure the expression of HAGLR, miR-185-5p in colon cancer. The expression of CDK4 and CDK6 was detected by Western blot. CCK-8 assay, EdU staining, transwell and Annexin V-FITC/PI assay were used to analyze the effect of HAGLR and miR-185-5p on cell proliferation, invasion, migration and apoptosis. Bioinformatic analysis and luciferase were used to analyze the target genes of HAGLR and miR-185-5p. Nude mice were used to detect mouse tumor changes. RESULTS: Compared with normal colon cancer tissues and cells, the expression of HAGLR was increased in colon cancer tissues and cells. In addition, the expression of HAGLR down-regulation inhibited the growth, migration, and invasion of colon cancer cells. MiR-185-5p was reduced in colon cancer, and CDK4 and CDK6 acted as target genes of miR-185-5p to regulate the progress of colon cancer. And CDK4 and CDK6 were predicted as downstream targets of miR-185-5p. Finally, it was demonstrated that HAGLR regulated tumor progression in vivo. CONCLUSION: Lnc HAGLR promoted the development of colon cancer by miR-185-5p/CDK4/CDK6 axis, and lnc HAGLR might be potential target for colon cancer.

Platelet­derived growth factor D promotes the angiogenic capacity of endothelial progenitor cells.

Neovascularization and re-endothelialization rely on endothelial progenitor cells (EPCs). However, the recruitment and angiogenic roles of EPCs are subject to regulation through the vascular microenvironment, which remains largely unknown. Platelet­derived growth factor D (PDGF­D) is a new member of the PDGF family that binds the PDGFR­ß homodimer. However, it remains unknown whether and how it affects the angiogenic capacity of EPCs and participates in tube­like formation. EPCs were derived from rat bone marrow cells, and the gain­of­function approach was used to study the effects of PDGF­D on the biological activities of EPCs. EPCs that stably express PDGF­D were generated by lentiviral­mediated transduction, and the expression levels were evaluated by western blotting and reverse transcription, followed by real­time quantitative polymerase chain reaction (RT­qPCR). The biological activities of EPCs evaluated in the present study included proliferation, adhesion, migration, tube formation and senescence. Furthermore, the downstream signaling of PDGF­D was explored by western blot analysis. The results revealed that the lentiviral­mediated expression of PDGF­D in the microenvironment promoted the migration, proliferation, adhesion and tube formation of EPCs. In addition, PDGF­D suppressed the senescence of EPCs. Mechanistically, PDGF­D induced the phosphorylation of several signaling molecules, including STAT3, AKT, ERK1/2, mTOR and GSK­3ß, suggesting that PDGF­D enhanced the angiogenic function of EPCs through PDGF receptor­dependent and ­independent signaling pathways. In conclusion, PDGF­D promotes the angiogenic capacity of EPCs, including proliferation, migration, adhesion and tube formation, and thereby contributes to angiogenesis.

Non-Esterified Fatty Acids Over-Activate the TLR2/4-NF-Κb Signaling Pathway to Increase Inflammatory Cytokine Synthesis in Neutrophils from Ketotic Cows.

BACKGROUND/AIMS: Dairy cows with clinical ketosis display a negative energy balance and high blood concentrations of non-esterified fatty acids (NEFAs), the latter of which is an important pathological factor of ketosis in cows. The aims of this study were to investigate the inflammatory status of ketotic cows and to determine whether and through what underlying mechanism high levels of NEFAs induce an inflammatory response. METHODS: Proinflammatory factors and the nuclear factor kappa B (NF-κB) signaling pathway were evaluated in neutrophils from clinical ketotic and control cows, using methods including western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. In vitro, the effects of NEFAs on the NF-κB signaling pathway in cow neutrophils were also evaluated using the above experimental techniques. RESULTS: Ketotic cows displayed low blood concentrations of glucose and high blood NEFA and ß-hydroxybutyrate concentrations. Importantly, Toll-like receptor 2 (TLR2) and TLR4 expression and IκBα and NF-κB p65 phosphorylation levels in neutrophils (PMNs) were significantly higher in ketotic cows than in control cows, indicating over-activation of the TLR2/4-induced NF-κB inflammatory pathway in PMNs in ketotic cows. The blood concentrations of the inflammatory cytokines interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) were also significantly increased in ketotic cows. Interestingly, we found that NEFAs were positively correlated with proinflammatory cytokines. In vitro, after pharmacological inhibition of TLR2 and TLR4 expression in cow neutrophils, TLR2 and TLR4 expression was significantly decreased, and the phosphorylation level of NF-κB p65 was also reduced. Cow neutrophils were treated with different concentrations of NEFAs and pyrrolidine dithiocarbamate (PDTC; an NF-κB inhibitor). High concentrations of NEFAs (0.5 and 1 mM) significantly increased TLR2 and TLR4 expression, IκBα and NF-κB p65 phosphorylation levels, NF-κB p65 transcriptional activity, and IL-6, IL-1ß, and TNF-α synthesis in cow neutrophils. The inhibition of NF-κB by PDTC suppressed the NEFA-induced synthesis of proinflammatory cytokines. CONCLUSIONS: High concentrations of NEFAs can over-activate the TLR2/4-mediated NF-κB signaling pathway to induce the over-production of proinflammatory cytokines, thereby increasing inflammation in cows with clinical ketosis.