Prognostic value of RNF113A shows a correlation with immune infiltrates in colorectal cancer.

OBJECTIVE: To explore the prognostic role of RNF113A in colorectal cancer (CRC) and its relationship with immune infiltration. METHODS: Data from publicly available datasets were collected and analyzed to evaluate RNF113A expression in different tumors compared with normal samples and investigate the relationship between RNF113A and CRC survival. The protein expression of RNF113A among colorectal cancer cell lines (HCT116, Caco2, Colon3) and human colorectal mucosa cell (FHC) was detected as well. Pathway enrichment analysis was performed to identify signaling pathways associated with RNF113A. The diagnostic and prognostic values of RNF113A expression in CRC and its correlation with cancer immune characteristics were analyzed by using the TIMER and TISIDB databases. RESULTS: RNF113A is predominantly overexpressed in CRC, which has diagnostic and prognostic value. The protein expression of RNF113A in Colon3 cells was significantly higher than that of FHC cells (P<0.05). The rRNA processing signaling pathway-related gene SNU13 was positively correlated with RNF113A (R=0.245, P<0.001). The area under the ROC curve (AUC) of RNF113A expression for diagnosis of CRC was 0.885. The nomogram showed that RNF113A expression outperformed traditional clinical features such as age in predicting prognosis. RNF113A expression was negatively correlated with the infiltration level of memory B cells, NK cells, Th2 cells, and CD8+ T cells. Moreover, RNF113A expression was negatively correlated with the expression of CCL4, CXCL16, CCR5, and CXCR4. CONCLUSION: RNF113A may regulate CRC through the rRNA processing pathway and negatively correlate with the infiltration level of immune cells, serving as a prognostic biomarker for CRC.

Unraveling the role of microRNAs: potential biomarkers for gestational diabetes mellitus revealed through RNA sequencing analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) poses significant health risks for both mothers and children, contributing to long-term complications such as type 2 diabetes and cardiovascular disease. This study explores the potential of microRNAs (miRNAs) as biomarkers for GDM by analyzing peripheral blood samples from GDM patients. METHOD: Ten samples, including peripheral blood from 5 GDM patients and 5 controls, were collected to perform the RNA sequencing analysis. Differentially expressed miRNAs were further validated by quantitative real-time polymerase chain reaction. RESULTS: A total of 2287 miRNAs were identified, 229 of which showed differential expression. Validation by qRT-PCR confirmed significant up-regulation of miR-5193, miR-5003-3p, miR-3127-5p, novel-miR-96, miR-6734-5p, and miR-122-5p, while miR-10395-3p was down-regulated. Bioinformatics analyses revealed the involvement of these miRNAs in pathways associated with herpes simplex virus 1 infection. CONCLUSION: This study provides insights into the differential expression of miRNAs in GDM patients and their potential roles in disease pathogenesis. It suggests that the differentially expressed miRNAs could serve as potential biomarkers for GDM, shedding light on the complex molecular mechanisms involved.

Inhibition of Lck/Fyn kinase activity promotes the differentiation of induced Treg cells through AKT/mTOR pathway.

Regulatory T (Treg) cells are indispensable in maintaining the immune homeostasis and preventing autoimmune diseases. Regulatory T (Treg) cells include thymus derived Treg cells (tTregs) and peripherally induced Treg cells (iTreg), which are differentiated from antigen stimulated CD4+ naïve T cells in presence of TGFß. tTregs are quite stable, and more immune suppressive, while iTreg cells are less stable, and are prone to differentiate into inflammatory T cells. Therefore, identification of small molecules that could promote the differentiation of iTreg cells is an attractive strategy for autoimmune diseases. Inhibition of AKT/mTOR pathway promotes their differentiation. Whether inhibition of Lck/Fyn kinase activity (upstream of AKT/mTOR pathway) can be used to promote the differentiation of iTreg cells has not been determined. Here, we showed that Srci1, a small molecular inhibitor of Lck/Fyn, promoted the differentiation of FOXP3+ iTreg cells. Srci1 treatment resulted in inhibition of phosphorylation of key components of AKT/mTOR pathway, including mTOR, p70 S6K, 4EBP1, and promoted the expression of Foxp3 and its target genes, thereby promoted differentiation of in vitro iTreg cells. Srci1 treated iTreg cells showed more similar gene expression profile to that of tTreg cells. Our results thus suggest that inhibition of Lck/Fyn kinase activity can promote the differentiation of iTreg cells, and may have implication in autoimmune diseases.

MUC16 can Predict the Pregnancy Outcomes in Human and Intraperitoneal Administration of MUC16 can Rescue Pregnancy Losses in Mouse Models.

Mucin 16 (MUC16) participates in the process of embryo implantation, but few studies have examined the association between MUC16 and pregnancy loss. To investigate this association, the expression of MUC16 in serum and decidua was compared between women with pregnancy loss and ongoing pregnancies. In vitro experiments and animal models were used to explore the role and underlying mechanisms of MUC16 in pregnancy loss. In human study, the expression of MUC16 in serum and decidua was both consistently lower in the women with pregnancy loss compared with those in women with ongoing pregnancies. In vitro experiments revealed the interaction of MUC16 with peripheral blood natural killer (pNK) cells. MUC16 changed the phenotype and reduced the pro-inflammation ability of pNK cells. MUC16 also inhibited the cytotoxicity of pNK cells through the Src homology region 2 domain-containing phosphatase-1/extracellular signal-regulated kinase (SHP-ERK) pathway. Furthermore, MUC16 promoted the migration, invasion and tube formation of trophoblast cells by co-culturing together with pNK cells. In vivo experiments, the mouse model of abortion was used to further confirm that intraperitoneal administration of MUC16 could rescue the pregnancy loss. This study reveals the still-unknown connection between MUC16 and pNK cells and indicates that MUC16 provides a novel method for future prediction and treatment of unfavorable pregnancy outcomes.

In situ and self-adaptive BOD bioreaction sensing system based on environmentally domesticated microbial populations.

Biochemical oxygen demand (BOD) is a water quality parameter of vital importance. Rapid BOD analysis methods have emerged to simplify the five-day BOD (BOD5) measurement protocol. However, their universal implementations are restricted by the tricky environmental matrix (including environmental microbes, contaminants, ionic compositions, etc.). Here, an in situ and self-adaptive BOD bioreaction sensing system consisting of a "gut-like" microfluidic coil bioreactor with self-renewed biofilm was proposed for the establishment of a rapid, resilient and reliable BOD determination method. With the spontaneous surface adhesion of environmental microbial populations, the biofilm was colonized in situ on the inner surface of the microfluidic coil bioreactor. Exploiting the environmental domestication during every real sample measurement, the biofilm was capable of self-renewal to adapt to the environmental changes and exhibited representative biodegradation behaviors. The aggregated abundant, adequate and adapted microbial populations in the BOD bioreactor rendered a total organic carbon (TOC) removal rate of 67.7% within a short hydraulic retention time of 99 s. As validated by an online BOD prototype, exceptional analytical performance was achieved in terms of reproducibility (relative standard deviation of 3.7%), survivability (inhibition by pH and metal ion interference of <20%) and accuracy (relative error of -5.9% to 9.7%). This work rediscovered the interactive effects of the environmental matrix on BOD assays and demonstrated an instructive attempt by making use of the environment to develop practical online BOD monitoring devices for water quality assessments.

The impact of endometrial scratch performed in mid-luteal phase on the endometrium whole genome transcriptomic profiles in following menstrual cycle.

The value of endometrial scratch in women with recurrent embryo transfer has been controversial. Endometrial scratch is often performed in the mid-luteal phase of the cycle preceding embryo transfer but there is little scientific evidence if it affects the whole genome transcriptomic profile of peri-implantation endometrium in the following cycle. A prospective longitudinal cohort study was conducted in a university assisted reproductive unit. A total of eight women with recurrent implantation failure (RIF) were included. Each participant had endometrial biopsy twice, first biopsy on day LH + 7 in natural cycle and second on day LH + 7 of the following cycle. R package was used to identify differentially expressed genes between the sample and enriched gene ontology. However, the paired sample showed no significant difference, neither known endometrial receptive gene set nor other genes, before and after the endometrial scratch. It suggests that endometrial scratch performed during previous mid-luteal phase did not affect the transcriptomic profiles of endometrium on day LH + 7 in women with RIF.

Low-dose human chorionic gonadotropin supplementation initiated at the onset of ovarian stimulation can improve oocyte quality without impairing endometrial receptivity: Case series.

RATIONALE: Whether continuous low-dose human chorionic gonadotropin (hCG) supplementation during controlled ovarian hyperstimulation (COH) can improve oocyte and embryo quality is still controversial in clinical practice. PATIENT CONCERNS: We report the first case series of inadvertent COH in luteal-phase stimulation in the presence of endogenous or exogenous low-dose hCG. DIAGNOSES: Patients were diagnosed with infertility. OUTCOMES: The first two cases had inadvertent COH during preexisting pregnancy, and one of which produced more high-quality embryos (5 vs 1) in the presence of low hCG. Both cases had a live birth. The third case had 7 repeated failures of IVF, during which a total of 55 oocytes were obtained, but only 3 developed into transferable embryo. However, supplementation of 330 IU hCG per day from the onset of COH resulted in the recovery of one high-quality embryo and subsequent delivery of a healthy baby following fresh embryo transfer in eighth attemption. LESSONS: In conclude, supplementation with low-dose hCG from the onset of ovarian stimulation can improve oocyte quality without impairing endometrial receptivity.

Toxicity from a single injection of human umbilical cord mesenchymal stem cells into rat ovaries.

Intraovarian injection of human umbilical cord mesenchymal stem cells (hUC-MSCs) has been applied and with promising therapeutic effects, but its toxicity and safety remain uncertain. This study evaluated the toxic effects and the affected target organs after a single injection of hUC-MSCs into bilateral rat ovaries. Sixty Sprague-Dawley rats were randomly divided into four groups and intraovarian injected with three different doses of hUC-MSC suspension. Toxicity-related manifestations occurred over the following 14 days postinjection. On day (D)5 and D15, we assessed the clinical pathology; immunotoxicity, including the cytokine IFN-γ, TNF-α, IL-4, and IL-6 levels; the immune organs, and the organ weights. On D5, inflammatory cells mainly infiltrated the ovaries of the low- and medium-dose groups, whereas inflammatory cells infiltrated the oviduct in the medium- and high-dose groups. On D15, inflammatory cells infiltrated the corpus luteal cysts, ovarian sacs and oviducts in each group. Body weights; organ weights; immunotoxicity; clinical pathology and histopathological examinations of the immune organs did not significantly differ among the groups. No obvious hUC-MSC-related clinical symptoms were observed except in the rats that died. The high-dose group exhibited significantly higher mortality than did the control and low-dose groups. Deaths in the high-dose group, who received approximately 50 times the standard clinical dose, were related to the intraovarian hUC-MSC injection. The maximum tolerated dose was approximately ten times the standard clinical dose. The ovary and oviduct may be the target organs for this toxicity. This report provides dosage references and guidance for clinical applications of intraovarian hUC-MSC injections.

Potentiating CD8+ T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling.

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8+ T cell antitumor activity. Besides the involvement of cholesterol uptake which is mediated by LDLR in T cell priming and clonal expansion, we also found a non-canonical function of LDLR in CD8+ T cells: LDLR interacts with the T-cell receptor (TCR) complex and regulates TCR recycling and signaling, thus facilitating the effector function of cytotoxic T-lymphocytes (CTLs). Furthermore, we found that the tumor microenvironment (TME) downregulates CD8+ T cell LDLR level and TCR signaling via tumor cell-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) which binds to LDLR and prevents the recycling of LDLR and TCR to the plasma membrane thus inhibits the effector function of CTLs. Moreover, genetic deletion or pharmacological inhibition of PCSK9 in tumor cells can enhance the antitumor activity of CD8+ T cells by alleviating the suppressive effect on CD8+ T cells and consequently inhibit tumor progression. While previously established as a hypercholesterolemia target, this study highlights PCSK9/LDLR as a potential target for cancer immunotherapy as well.

Interleukin-6 in Patients with Cardiac Myxoma.

The relationships between interleukin (IL)-6 and cardiac myxoma remain to be clarified. This article systematically reviewed the IL-6 properties in cardiac myxoma patients based on retrieval of pertinent literature published between 1998 and 2018. Significant differences were found in circulating IL-6 values between preoperation and 1 and 6 months after operation. Preoperative circulating IL-6 correlated significantly with tumour volume (r=0.8552, p=0.003), while there were no significant correlations with maximal tumour dimension (r=0.2443, p=0.190). No correlation was found between circulating IL-6 at 1 and 6 months after tumour resection with either tumour volume or with maximal tumour dimension. The positive rate of immunostaining of IL-6 in cardiac myxoma tissues was 93.3%. Overproduction of IL-6 is responsible for the inflammatory presentations, constitutional symptoms, and recurrence and distal embolisation of cardiac myxoma. Cardiac myxoma could be a cellular source of IL-6 release. Cardiac myxoma resection is an absolute choice of eliminating IL-6 production in these patients. Key Words: Cardiac surgical procedures, Cytokines; Inflammation, Interleukin-6, Neoplasms.

Coronary artery involvements in Takayasu arteritis: systematic review of reports.

Coronary artery involvements in patients with Takayasu arteritis (TA) have not been sufficiently described. By comprehensive retrieval of the pertinent literature published in the past two decades, 59 reports including 141 patients were recruited into this study. In TA patients with coronary artery involvements, the right coronary artery was the most commonly affected. Stenosis was the most common coronary artery lesion, and the coronary ostium was the most commonly affected coronary segment. Acute myocardial infarction was diagnosed in 17 (12.1%) patients of this cohort. Patients receiving surgical treatment showed a higher recovery rate than interventionally treated patients. Interventional therapy was associated with a higher reintervention rate than surgical treatment. The inflammation condition in TA patients can lead to in-stent restenosis and warrant reinterventions. Surgical treatment is a preferable treatment of choice over interventional therapy for the coronary artery lesions of TA patients.

Predictors of Normalization of Circulating Interleukin-6 after Cardiac Myxoma Resection.

OBJECTIVE: To disclose the relationships between the anatomic features of cardiac myxomas and plasma interleukin (IL)-6 levels. METHODS: Twelve patients undergoing cardiac myxoma resection at The First Hospital of Putian, Teaching Hospital, Fujian Medical University were enrolled into this study. Pre- and postoperative IL-6 levels were determined by an enzyme-linked immunosorbent assay method, and correlations between cardiac myxoma dimension or volume and plasma IL-6 levels were analyzed. C-reactive protein (CRP) levels were also evaluated. RESULTS: IL-6 and CRP levels were significantly decreased one month after cardiac myxoma resection in comparison to preoperative values. IL-6 and CRP levels did not differ between patients with a cardiac myxoma of irregular appearance and those with a myxoma of regular gross appearance, or between patients with a pedicled or a sessile myxoma. Decrement of IL-6 of patients with irregular cardiac myxomas was much higher than that of patients with regular ones, while no intergroup difference was noted in decrement of CRP. A close direct correlation was noted between IL-6 levels and maximal dimension (length) or volume of cardiac myxomas, whereas CRP levels only correlated with maximal dimension of cardiac myxomas. CONCLUSION: Anatomic features of cardiac myxomas (sessile, irregular appearance, maximal dimension, and volume) could be determinants of the patients' circulating IL-6 levels. IL-6 was likely to be a more sensitive biomarker than CRP in predicting the inflammatory status of patients with cardiac myxoma. Sessile and irregular cardiac myxomas might predict more severe inflammatory conditions for their more abundant endothelial cells and IL-6 overproduction.

Predictors of normalization of circulating interleukin-6 after cardiac myxoma resection

Abstract Objective: To disclose the relationships between the anatomic features of cardiac myxomas and plasma interleukin (IL)-6 levels. Methods: Twelve patients undergoing cardiac myxoma resection at The First Hospital of Putian, Teaching Hospital, Fujian Medical University were enrolled into this study. Pre- and postoperative IL-6 levels were determined by an enzyme-linked immunosorbent assay method, and correlations between cardiac myxoma dimension or volume and plasma IL-6 levels were analyzed. C-reactive protein (CRP) levels were also evaluated. Results: IL-6 and CRP levels were significantly decreased one month after cardiac myxoma resection in comparison to preoperative values. IL-6 and CRP levels did not differ between patients with a cardiac myxoma of irregular appearance and those with a myxoma of regular gross appearance, or between patients with a pedicled or a sessile myxoma. Decrement of IL-6 of patients with irregular cardiac myxomas was much higher than that of patients with regular ones, while no intergroup difference was noted in decrement of CRP. A close direct correlation was noted between IL-6 levels and maximal dimension (length) or volume of cardiac myxomas, whereas CRP levels only correlated with maximal dimension of cardiac myxomas. Conclusion: Anatomic features of cardiac myxomas (sessile, irregular appearance, maximal dimension, and volume) could be determinants of the patients' circulating IL-6 levels. IL-6 was likely to be a more sensitive biomarker than CRP in predicting the inflammatory status of patients with cardiac myxoma. Sessile and irregular cardiac myxomas might predict more severe inflammatory conditions for their more abundant endothelial cells and IL-6 overproduction.