Moyamoya syndrome may result from psoriasis: Four case reports.

BACKGROUND: Moyamoya syndrome (MMS) is a group of diseases that involves more than one underlying disease and is accompanied by moyamoya vascular phenomena. Psoriasis is a chronic immune skin disease closely linked to high blood pressure and heart disease. However, psoriasis-related MMS has not been reported. CASE SUMMARY: We collected data on patients with stroke due to MMS between January 2017 and December 2019 and identified four cases of psoriasis. Case histories, imaging, and hematological data were collected. The average age of the initial stroke onset was 58.25 ± 11.52 years; three cases of hemorrhagic and one case of ischemic stroke were included. The average duration from psoriasis confirmation to the initial MMS-mediated stroke onset was 17 ± 3.56 years. All MMS-related stenoses involved the bilateral cerebral arteries: Suzuki grade III in one case, grade IV in two cases, and grade V in one case. Abnormally elevated plasma interleukin-6 levels were observed in four patients. Two patients had abnormally elevated immunoglobulin E levels, and two had thrombocytosis. All four patients received medication instead of surgery. With an average follow-up time of 2 years, two causing transient ischemic attacks occurred in two patients, and no hemorrhagic events occurred. CONCLUSION: Psoriasis may be a potential risk factor for MMS. Patients with psoriasis should be screened for MMS when they present with neurological symptoms.

Targeting NAD metabolism regulates extracellular adenosine levels to improve the cytotoxicity of CD8+ effector T cells in the tumor microenvironment of gastric cancer.

PURPOSE: Nicotinamide adenine dinucleotide (NAD+) is closely related to the pathogenesis of tumors. However, the effect of NAD+ metabolism of gastric cancer (GC) cells on immune cells remains unexplained. We targeted nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD+ synthesis salvage pathway, to observe its effect in the immune microenvironment. METHODS: NAMPT of GC cell lines was inhibited by using the small molecule inhibitor (FK866) and short hairpin RNA (shRNA). CCK-8 test and flow cytometry were performed to detect cell viability and apoptosis. Immunofluorescence was used to observe changes in mitochondrial membrane potential (MMP).The transfected GC cells (AGS) and patient-derived organoids (PDOs) were cocultured with activated PBMCs, followed by flow cytometric analysis (FCA) for cytokines and inhibitory marker. The level of NAD and ATP of GC cells (AGS & MKN45) was tested combined with NMN and CD39 inhibitor. RESULTS: Targeting NAD+ by FK866 obviously reduced MMP, which ultimately inhibited proliferation and increased the apoptosis of GC cells. NAMPT silencing reduced intracellular NAD and ATP，further decreased extracellular adenosine. Meawhile, the cytokines of CD8+T cells were significantly increased after cocultured with transfected AGS, and the expression of PD-1 was distinctly decreased. NMN reversed the effect of shNAMPT and enhanced the immunosuppression. Consistent results were obtained by coculturing PBMCs with PDOs. CONCLUSION: Restraining the function of NAMPT resulted in the functional improvement of effector CD8+ T cells by decreasing extracellular adenosine levels and inducing apoptosis of GC cells simultaneously. Therefore, this study demonstrates that NAMPT can be an effective target for gastric cancer immunotherapy.

The Prognostic Effect of Multidisciplinary Team Intervention in Patients with Advanced Gastric Cancer.

BACKGROUND: The effect of multidisciplinary team intervention (MDT) on the prognosis of advanced gastric cancer (GC) is still controversial. This study aims to analyze the effect of MDTs on the overall survival time of advanced gastric cancer patients. METHODS: Patients with advanced GC who underwent surgical treatment between 2007 and 2014 were included in the study. They were divided into two groups; the MDT group received MDT treatment and the non-MDT group received conventional treatment. The Kaplan-Meier method was used to compare the overall survival (OS) of the two groups. The prognostic factors of advanced GC were evaluated by multivariate Cox regression analysis. RESULTS: 394 patients were included in our study. Kaplan-Meier survival analysis showed that the prognosis of advanced GC patients with who underwent MDT intervention was better than those without (3-year OS of 55.6% vs. 46.1%, p = 0.005), Multivariate analysis indicated that MDT intervention could reduce mortality (HR = 0.493, p < 0.001). CONCLUSIONS: MDT intervention is an effective measure that improves the survival of patients with advanced GC.

LncRNA-GAS5 related to the processes of recurrent pregnancy loss by regulating Th1/Th2 balance.

Recurrent pregnancy loss (RPL) is defined as three or more consecutive spontaneous loss of pregnancy and the reason of 50% RPL is unknown. GAS5 is a long non-coding RNA, which has been found to be an immune responses regulator and to be relate to autoimmune diseases. However, the roles of GAS5 during the pathophysiological processes of RPL is unclear. In the present study, the levels of GAS5 were examined in the plasma and trophoblasts from 30 patients with RPL and 15 healthy controls. GAS5 was found overexpressed in patients with RPL and positively correlated with the protein levels of TNF-α in the plasma and trophoblasts. Predicted by bioinformatics tools and confirmed by luciferase assay, GAS5 was identified to function as a competing endogenous RNA (ceRNA) binding with miR-140-5p and protects TNF-α expression in HTR-8/SVneo cells and primary trophoblasts. Activated Naïve T cells co-cultured with the medium from GAS5 overexpression HTR-8/SVneo cells or primary trophoblasts exhibited Th1 bias by expression more IFN-γ, TNF-α and less IL-4, IL-10. In conclusion, GAS5 was overexpressed in the plasma and trophoblasts from RPL patients, which contributes to Th1 bias by binding with miR-140-5p.

Mine disaster survivor's pelvic floor hernia treated with laparoscopic surgery and a perineal approach: A case report.

BACKGROUND: A pelvic floor hernia is defined as a pelvic floor defect through which the intraabdominal viscera may protrude. It is an infrequent complication following abdominoperineal surgeries. This type of hernia requires surgical repair by conventional or reconstructive techniques. The main treatments could be transabdominal, transperineal or a combination. CASE SUMMARY: In this article, we present the case of a recurrent perineal incisional hernia, postresection of the left side of the pelvis, testis and lower limbs resulting from a mine disaster 18 years ago. Combined laparoscopic surgery with a perineal approach was performed. The pelvic floor defect was repaired by a biological mesh and one pedicle skin flap. No signs of recurrence were indicated during the 2 years of follow-up. CONCLUSION: The combination of laparoscopic surgery with a perineal approach was effective. The use of the biological mesh and pedicle skin flap to restructure the pelvic floor was effective.

Clinical evaluation of endoscopic resection for treatment of large gastric stromal tumors.

BACKGROUND: Gastric stromal tumor is a digestive tract mesenchymal tumor with malignant potential, and endoscopic techniques have been widely used in the treatment of gastric stromal tumors, but there is still controversy over their use for large gastric stromal tumors (≥ 3 cm). AIM: To evaluate the clinical long-term efficacy and safety of endoscopic resection for large (≥ 3 cm) gastric stromal tumors. METHODS: All patients who underwent endoscopic resection or surgery at our hospital from 2012 to 2017 for pathologically confirmed gastric stromal tumor with a maximum diameter of ≥ 3 cm were collected. The clinical data, histopathologic characteristics of the tumors, and long-term outcomes were recorded. RESULTS: A total of 261 patients were included, including 37 patients in the endoscopy group and 224 patients in the surgical group. In the endoscopy group, the maximum tumor diameter was 3-8 cm; the male: Female ratio was 21/16; 34 cases had low-risk tumors, 3 had intermediate-risk, and 0 had high-risk; the mean follow-up time was 30.29 ± 19.67 mo, no patient was lost to follow-up, and no patient received chemotherapy after operation; two patients with recurrence had low-risk stromal tumors, and neither had complete resection under endoscopy. In the surgical group, the maximum tumor diameter was 3-22 cm; the male: Female ratio was 121/103; 103 cases had low-risk tumors, 75 had intermediate-risk, and 46 had high-risk; the average follow-up time was 38.83 ± 21.50 mo, 53 patients were lost to follow-up, and 8 patients had recurrence after operation (6 cases had high-risk tumors, 1 had intermediate-risk, and 1 had low-risk). The average tumor volume of the endoscopy group was 26.67 ± 26.22 cm3 (3.75-120), all of which were less than 125 cm3. The average volume of the surgical group was 273.03 ± 609.74 cm3 (7-4114). Among all patients with a tumor volume < 125 cm3, 7 with high-risk stromal tumors in the surgical group (37.625 cm3 to 115.2 cm3) accounted for 3.8% (7/183); of those with a tumor volume < 125 cm3, high-risk patients accounted for 50% (39/78). We found that 57.1% (12/22) of patients with high-risk stromal tumors also had endoscopic surface ulcer bleeding and tumor liquefaction on ultrasound or abdominal computed tomography; the ratio of tumors positive for both in high-risk stromal tumors with a volume < 125 cm3 was 60% (3/5). CONCLUSION: Endoscopic treatment is safe for 95.5% of patients with gastric stromal tumors with a tumor diameter ≥ 3 cm and a volume of < 125 cm3 without endoscopic surface ulcer bleeding or CT liquefaction.

Downregulation of long noncoding RNA DGCR5 contributes to the proliferation, migration, and invasion of cervical cancer by activating Wnt signaling pathway.

Accumulating research works have reported that long noncoding RNAs (lncRNAs) are involved in various cancers, including cervical cancer. LncRNA DGCR5 has been identified in many cancers. However, the biological role of DGCR5 in cervical cancer remains barely known. We aimed to investigate the biological function of DGCR5 in cervical cancer progression. Here, in our current study, we observed that DGCR5 was downregulated in human cervical cancer cell lines (MS751, SiHa, HeLa, and HT-3) compared with the primary normal cervical squamous cells (NCSC1 and NCSC2). Then, DGCR5 was restrained by transfection with lenti-virus-short hairpin RNA (LV-shRNA) while induced by LV-DGCR5 in HeLa and C33A cells. Silence of DGCR5 obviously induced cervical cancer cell viability and cell proliferation. Reversely, upregulation of DGCR5 inhibited HeLa and C33A cell survival and proliferation. Furthermore, silencing of DGCR5 increased cervical cancer cell colony formation ability and decreased cell apoptosis, whereas its overexpression exhibited an opposite process. Moreover, DGCR5 suppressed migration and invasion capacity of cervical cancer cells. The Wnt signaling is integral in numerous biological processes. Here, we found that Wnt signaling was strongly activated in cervical cancer cells. Downregulation of DGCR5 contributed to cervical cancer progression by activating Wnt signaling. Subsequently, in vivo animal models were used to confirm that DGCR5 suppressed cervical cancer via targeting Wnt signaling. In conclusion, we reported that DGCR5 was involved in cervical cancer progression via modulating the Wnt pathway.

New progress in roles of nitric oxide during hepatic ischemia reperfusion injury.

Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothelial nitric oxide synthase (eNOS) activation plays a protective role during early HIRI. But eNOS overexpression and the resulting excessive NO bioavailability can aggravate liver injury. NO induced by inducible nitric oxide synthase (iNOS) may have either a protective or a deleterious effect during the early phase of HIRI, but it may protect the liver during late HIRI. Here, we reviewed the latest findings on the role of NO during HIRI: (1) NO exerts a protective effect against HIRI by increasing NO bioavailability, downregulating p53 gene expression, decreasing inflammatory chemokines, reducing ROS via inhibiting the mitochondrial respiratory chain, activating sGC-GTP-cGMP signal pathway to reduce liver cell apoptosis, and regulating hepatic immune functions; (2) eNOS protects against HIRI by increasing NO levels, several eNOS/NO signal pathways (such as Akt-eNOS/NO, AMPK-eNOS/NO and HIF-1α-eNOS/NO) participating in the anti-HIRI process, and inhibiting over-expression of eNOS also protects against HIRI; and (3) the inhibition of iNOS prevents HIRI. Thus, the adverse effects of NO should be avoided, but its positive effect in the clinical treatment of diseases associated with HIRI should be recognized.

Overexpression of Hsa-miR-320 Is Associated With Invasion and Metastasis of Ovarian Cancer.

Ovarian cancer is one of the most common malignant tumor of female genital organs which ranks the third morbidity. We aimed to provide a better understanding of the mechanism of invasion and metastasis of ovarian cancer. The ovarian cancer samples were downloaded from GEO. Then clustering was performed to classify the stage of miRNAs based on the difference of prognosis and metastasis. Furthermore, the miRNAs model was build and the survival analysis processes was performed to observe the influence on prognosis, invasion and metastasis. At last, miRNAs co-expression network was built to explore the core miRNAs and the risk classification model was built to perform the risk assessment based on these core miRNAs. A total of 17 significantly differential expressed miRNAs were obtained. Functional enrichment of 1,488 target genes, pathways like cell cycle, focal adhesion, and pathways in cancer, which are closely related to the proliferation and metastasis of cancer cells were highly enriched, this indicate that these miRNAs are related to the proliferation and metastasis of cancer cells. The co-expressed network shows that the high expression of hsa-miR-320 indicated negative prognosis and high risk of metastasis. In conclusion, the expression level of hsa-miR-320 is highly related to the migration and invasion of cancer. The high expression of hsa-miR-320 directly indicated negative prognosis and high risk of metastasis. These findings reveal that hsa-miR-320 may serve as an important therapeutic target in ovarian cancer therapy. J. Cell. Biochem. 118: 3654-3661, 2017. © 2017 Wiley Periodicals, Inc.

Competing endogenous RNA interplay in cancer: mechanism, methodology, and perspectives.

Competing endogenous RNAs (ceRNAs) refer to RNA transcripts, such as mRNAs, non-coding RNAs, pseudogene transcripts, and circular RNAs, that can regulate each other by competing for the same pool of miRNAs. ceRNAs involve in the pathogenesis of several common cancers such as prostate cancer, liver cancer, breast cancer, lung cancer, gastric cancer, endometrial cancer, and so on. ceRNA activity is determined by factors such as miRNA/ceRNA abundance, ceRNAs binding affinity to miRNAs, RNA editing, and RNA-binding proteins. The alteration of any of these factors may lead to ceRNA network imbalance and thus contribute to cancer initiation and progression. There are generally three steps in ceRNA research conductions: ceRNA prediction, ceRNA validation, and ceRNA functional investigation. Deciphering ceRNA interplay in cancer provides new insight into cancer pathogenesis and opportunities for therapy exploration. In this review, we try to give readers a concise and reliable illustration on the mechanism, functions, research approaches, and perspective of ceRNA in cancer.