LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B.

BACKGROUND: LncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown. METHODS: The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay. RESULTS: We demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein. CONCLUSIONS: Overall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM.

The association between dietary mineral intake and the risk of preeclampsia in Chinese pregnant women: a matched case-control study.

Previous studies on the relationship between dietary minerals and preeclampsia (PE) have given inconsistent results. The aim of this study was to further clarify the relationship between dietary minerals intake and PE in Chinese pregnant women. In this study, 440 pairs of hospital-based preeclamptic and healthy women were matched 1:1. Dietary intake was obtained through a 78-item semi-quantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were plotted to evaluate the dose-response relationship between dietary minerals intake and PE. This study found significant inverse associations for dietary intake of calcium, magnesium, phosphorus, iron, copper, manganese and zinc and the risk of PE in both univariate and multivariate models (all P- trend < 0.05). After adjusting for possible confounders, compared with the lowest quartile, the odds ratio of the highest quartile was 0.74 (95% CI 0.56-0.98) for calcium, 0.63 (95% CI 0.42-0.93) for magnesium, 0.45 (95% CI 0.31-0.65) for phosphorus, 0.44 (95% CI 0.30-0.65) for iron, 0.72 (95% CI 0.53-0.97) for copper, 0.66 (95% CI 0.48-0.91) for manganese and 0.38 (95% CI 0.25-0.57) for zinc. In addition, a reverse J-shaped relationship between dietary minerals intake and PE risk was observed (P-overall association < 0.05). In Chinese pregnant women, a higher intake of dietary minerals, including calcium, magnesium, phosphorus, copper, iron, manganese, and zinc was associated with a lower odds of PE.

BHLHE40, a potential immune therapy target, regulated by FGD5-AS1/miR-15a-5p in pancreatic cancer.

Pancreatic cancer, as one of the neoplasms with the highest degree of malignancy, has become a main disease of concerns in recent years. BHLHE40, a critical transcription factor for remodeling of the tumor immune microenvironment, has been described to be substantially increased in a variety of tumor-associated immune cells. Nevertheless, the pro-cancer biological functions and underlying molecular mechanisms of BHLHE40 for pancreatic cancer and its unique microenvironment are unclear. Hereby, we investigated the pro-oncogenic role of BHLHE40 in the pancreatic cancer microenvironment by bioinformatics analysis and cell biology experiments and determined that the expression of BHLHE40 was obviously elevated in pancreatic cancer tissues than in adjacent normal tissues. In parallel, Kaplan-Meier survival analysis unveiled that lower expression of BHLHE40 was strongly associated with better prognosis of patients. Receiver operating characteristic (ROC) curve analysis confirmed the accuracy of the BHLHE40-related prediction model. Subsequent, spearman correlation analysis observed that higher expression of BHLHE40 might be involved in immunosuppression of pancreatic cancer. Silencing of BHLHE40 could inhibit proliferation, invasion, and apoptosis of pancreatic cancer in vitro and in vivo, implying that BHLHE40 is expected to be a potential therapeutic target for pancreatic cancer. In addition, we explored and validated the FGD5-AS1/miR-15a-5p axis as a potential upstream regulatory mode for high expression of BHLHE40 in pancreatic cancer. In summary, our data showed that ceRNA involved in the regulation of BHLHE40 contributes to the promotion of immunosuppressive response in pancreatic and is expected to be a diagnostic marker and potential immunotherapeutic target for pancreatic cancer.

Dietary intake and serum concentrations of vitamin A and vitamin E and pre-eclampsia risk in Chinese pregnant women: A matched case-control study.

Background: Many studies have suggested that the serum concentrations of vitamin A (VA) and vitamin E (VE) influence preeclampsia (PE) risk in pregnant women. However, few studies have assessed whether dietary intake and serum concentrations of VA and VE are correlated with PE risk. Methods: A 1:1 matched case-control study was conducted to explore the association between the dietary intake and serum concentrations of VA and VE and the risk of PE in pregnant Chinese women. A total of 440 pregnant women with PE and 440 control pregnant women were included in the study. Dietary information was obtained using a 78-item semi-quantitative food frequency questionnaire. Serum concentrations of VA and VE were measured by liquid chromatography-tandem mass spectrometry. Results: Compared with the lowest quartile, the multivariate-adjusted odds ratios [95% confidence interval (CI)] of the highest quartiles were 0.62 (95% CI: 0.40-0.96, P trend = 0.02) for VA, 0.51 (95% CI: 0.33-0.80, P trend =0.002) for ß-carotene, and 0.70 (95% CI: 0.45-1.08, P trend = 0.029) for retinol. Additionally, for serum VA and VE concentrations, the multivariate-adjusted odds ratios (95% CI) were 2.75 (95% CI: 1.24-6.13, P trend = 0.002) and 11.97 (95% CI: 4.01-35.77, P trend < 0.001), respectively. No significant association was seen between VE intake and PE risk. Conclusions: Dietary VA intake was negatively correlated with PE risk, and serum VA and VE concentrations were positively correlated with PE risk among pregnant Chinese women.

One-carbon metabolism-related nutrients intake is associated with lower risk of preeclampsia in pregnant women: a matched case-control study.

Many studies have suggested that folate plays a role in preeclampsia (PE) risks, but few studies have assessed folate-related 1-carbon metabolism (OCM)-related nutrients with the risk of PE. We hypothesized that OCM-related nutrients are associated with PE. A 1:1 matched case-control study was conducted to explore the association between dietary OCM-related nutrients intake and the risk of PE in pregnant Chinese women. Four hundred and forty pairs of pregnant women with PE and hospital-based, healthy pregnant women, matched according to gestational week (±1 week) and age (±3 years), were recruited. Dietary intake was assessed using a validated 78-item semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. Restricted cubic splines were plotted to evaluate the dose-response relationship between dietary OCM-related nutrient intake and the risk of PE. Intake of folate, vitamin B6, vitamin B12, methionine, and total choline were inversely related to the risk of PE after adjustment for covariates (all P trend < .05). Adjusted ORs (95% CIs) for quartile 4 versus quartile 1 were 0.71 (0.55-0.93) for folate, 0.66 (0.50-0.87) for vitamin B6, 0.68 (0.52-0.88) for vitamin B12, 0.77 (0.60-0.81) for methionine, and 0.67 (0.51-0.87) for total choline. This study suggests that dietary OCM-related nutrients intake is associated with lower odds of PE in pregnant Chinese women.

Noncirrhotic portal hypertension due to peripheral T-cell lymphoma, not otherwise specified: A case report.

BACKGROUND: Peripheral T-cell lymphoma (PTCL), an aggressive and rare disease that belongs to a heterogeneous group of mature T-cell lymphomas, develops rapidly and has a poor prognosis. Early detection and treatment are essential to improve patient cure and survival rates. Here, we report a rare case of PTCL with clinical presentation of noncirrhotic portal hypertension, which provides a basis for early vigilance of lymphomas in the future. CASE SUMMARY: A 65-year-old Chinese woman was admitted to our hospital because of abdominal distension for 3 months and pitting oedema of both lower limbs for 2 months. Physical examinations and associated auxiliary examinations showed the presence of hepatosplenomegaly, and her hepatic venous pressure gradient was 10 mmHg. Immunohistochemical analysis of the liver biopsy confirmed the diagnosis of PTCL. The patient underwent combination therapy with dexamethasone, VP-16, and chidamide. Unfortunately, after 41 days of chemotherapy, the patient died of multiple organ failure. CONCLUSION: PCTL accompanied by noncirrhotic portal hypertension is rarely reported. This case report discusses the diagnosis of a patient according to the literature.

A Study on Insulation Monitoring Technology of High-Voltage Cables in Underground Coal Mines Based on Decision Tree.

The insulation state of high-voltage cables in coal mines directly influences the reliability of power supply in coal mines and the level of safe production. In this paper, the degradation mechanism of cable insulation is analyzed, and an online monitoring technology of cable insulation in coal mines based on decision tree is proposed, the technical principle of the judgment method of cable degradation based on decision tree is studied, the feasibility of this technology is verified through simulation, the existing online monitoring solutions for cable insulation are analyzed, and a wide-area synchronous measurement and monitoring system for cable insulation is designed. This technology has been applied in Chinese coal mine enterprises in China and achieved a good effect.

Associations of dietary patterns and pre-eclampsia: a matched case-control study.

Little is known about the effects of dietary patterns on prevalent pre-eclampsia in Chinese population. This study aimed to investigate the associations between dietary patterns and the odds of pre-eclampsia among Chinese pregnant women. A 1:1 age- and gestational week-matched case-control study was conducted between March 2016 and February 2019. A total of 440 pairs of pre-eclampsia cases and healthy controls were included. Dietary intakes were assessed by a seventy-nine-item FFQ and subsequently grouped into twenty-eight distinct groups. Factor analysis using the principal component method was adopted to derive the dietary patterns. Conditional logistic regression was used to analyse the associations of dietary patterns with prevalent pre-eclampsia. We identified four distinct dietary patterns: high fruit-vegetable, high protein, high fat-grain and high salt-sugar. We found that high fruit-vegetable dietary pattern (quartile (Q)4 v. Q1, OR 0·71, 95 % CI 0·55, 0·92, Ptrend = 0·013) and high protein dietary pattern (Q4 v. Q1, OR 0·72, 95 % CI 0·54, 0·95, Ptrend = 0·011) were associated with a decreased odds of pre-eclampsia in Chinese pregnant women. Whereas high fat-grain dietary pattern showed a U-shaped association with pre-eclampsia, the lowest OR was observed in the third quartile (Q3 v. Q1, OR 0·75, 95 % CI 0·57, 0·98, Ptrend = 0·111). No significant association was observed for high salt-sugar dietary pattern. In conclusion, pregnancy dietary pattern characterised by high fruit-vegetable or high protein was found to be associated with a reduced odds of pre-eclampsia in Chinese pregnant women.

Dietary carotenoid intake and risk of developing preeclampsia: a hospital-based case-control study.

BACKGROUND: The effect of carotenoids on the risk of preeclampsia (PE) is uncertain. We aimed to examine the associations between the intake of dietary carotenoids and related compounds by pregnant women in China, and the risk of their developing PE. METHODS: Four hundred and forty PE cases and 440 age- (± 3 years), gestational age- (± 1 weeks) and gestational diabetes mellitus status- (yes/no) matched healthy controls were recruited from March 2016 to June 2019. Dietary intake of carotenoids was assessed using a 79-item validated food-frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. RESULTS: After adjusting for potential confounders, we found that the intake of total carotenoids, ß-carotene, ß-cryptoxanthin, lycopene, and lutein and zeaxanthin (lut-zea) were negatively associated with the odds of developing PE. Compared with the lowest quartile intake, the multivariate-adjusted OR (95% CI) of the highest quartile intake was 0.29 (0.16-0.54, Ptrend <  0.001) for total carotenoids, 0.31 (0.16-0.58, Ptrend <  0.001) for ß-carotene, 0.50 (0.27-0.90, Ptrend = 0.007) for ß-cryptoxanthin, 0.55 (0.30-0.99, Ptrend = 0.04) for lycopene and 0.32 (0.17-0.61, Ptrend = 0.001) for lut-zea. However, no significant associations were observed between the risk of developing PE and α-carotene intake (OR = 0.75, 95% CI: 0.41-1.36, Ptrend = 0.28). Moreover, similar negative associations were found for every one-standard-deviation increase in the intake of total carotenoids, ß-carotene, ß-cryptoxanthin, lycopene and lut-zea. CONCLUSION: These results indicate that a high intake of total carotenoids, ß-carotene, ß-cryptoxanthin, lycopene and lut-zea may be associated with a low risk of developing PE.

Dietary inflammatory index, inflammation biomarkers and preeclampsia risk: a hospital-based case-control study.

This study evaluated the association between inflammatory diets as measured by the Dietary Inflammatory index (DII), inflammation biomarkers and the development of preeclampsia among the Chinese population. We followed the reporting guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology statement for observational studies. A total of 466 preeclampsia cases aged over 18 years were recruited between March 2016 and June 2019, and 466 healthy controls were 1:1 ratio matched by age (±3 years), week of gestation (±1 week) and gestational diabetes mellitus. The energy-adjusted DII (E-DII) was computed based on dietary intake assessed using a seventy-nine item semiquantitative FFQ. Inflammatory biomarkers were analysed by ELISA kits. The mean E-DII scores were -0·65 ± 1·58 for cases and -1·19 ± 1·47 for controls (P value < 0·001). E-DII scores positively correlated with interferon-γ (r s = 0·194, P value = 0·001) and IL-4 (r s = 0·135, P value = 0·021). After multivariable adjustment, E-DII scores were positively related to preeclampsia risk (Ptrend < 0·001). The highest tertile of E-DII was 2·18 times the lowest tertiles (95 % CI = 1·52, 3·13). The odds of preeclampsia increased by 30 % (95 % CI = 18 %, 43 %, P value < 0·001) for each E-DII score increase. The preeclampsia risk was positively associated with IL-2 (OR = 1·07, 95 % CI = 1·03, 1·11), IL-4 (OR = 1·26, 95 % CI = 1·03, 1·54) and transforming growth factor beta (TGF-ß) (OR = 1·17, 95 % CI = 1·06, 1·29). Therefore, proinflammatory diets, corresponding to higher IL-2, IL-4 and TGF-ß levels, were associated with increased preeclampsia risk.

[Analysis of SALL1 gene variant in a boy with Townes-Brocks syndrome without anal atresia].

OBJECTIVE: To explore the genetic basis for a child presented with renal failure and multi-cystic dysplastic kidney without anal atresia. METHODS: Peripheral blood sample of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: The 40-day-old infant had presented with vomiting brown matter in a 7 days neonate and was transferred for kidney failure. Clinical examination has discovered renal failure, polycystic renal dysplasia, congenital hypothyroidism, bilateral thumb polydactyly, sensorineural hearing loss and preauricular dermatophyte. Genetic testing revealed that he has harbored a previously unreported c.824delT, p.L275Yfs*10 frameshift variant of SALL1 gene, which was confirmed by Sanger sequencing as de novo. CONCLUSION: The patient was diagnosed with Townes-Brocks syndrome due to the novel de novo variant of SALL1 gene. Townes-Brocks syndrome without anal atresia is rare. Above finding has also enriched the mutational spectrum of the SALL1 gene.

Synthesis of rGO supported Cu@FeCo catalyst and catalytic hydrolysis of ammonia borane.

Highly dispersed Cu@FeCo/rGO catalysts have been prepared by two-step reduction method and used for hydrogen production from ammonia borane (NH3BH3, AB) hydrolysis at 298 K. The activity and reusability of synthesized composite catalyst were much more higher than Cu@FeCo for AB hydrolysis dehydrogenation at 298 K. Kinetic study manifested that AB hydrolysis dehydrogenation with Cu@FeCo/rGO catalysts was approaching to the first order at different catalyst concentrations. The hydrolysis reaction completed within four minutes, and its maximum hydrogen production rate reached to 7863.0 ml min-1 g-1 at 298 K.

Dietary and serum vitamin D and preeclampsia risk in Chinese pregnant women: a matched case-control study.

The effect of vitamin D (VD) on the risk of preeclampsia (PE) is uncertain. Few of previous studies focused on the relationship between dietary VD intake and PE risk. Therefore, we conducted this 1:1 matched case-control study to explore the association of dietary VD intake and serum VD concentrations with PE risk in Chinese pregnant women. A total of 440 pairs of participants were recruited during March 2016 to June 2019. Dietary information was obtained using a seventy-eight-item semi-quantitative FFQ. Serum concentrations of 25(OH)D2 and 25(OH)D3 were measured by liquid chromatography-tandem MS. Multivariate conditional logistic regression was used to estimate OR and 95 % CI. Restricted cubic splines (RCS) were plotted to evaluate the dose-response relationship of dietary VD intake and serum VD concentrations with PE risk. Compared with the lowest quartile, the OR of the highest quartile were 0·45 (95 % CI 0·29, 0·71, Ptrend = 0·001) for VD dietary intake and 0·26 (95 % CI 0·11, 0·60, Ptrend = 0·003) for serum levels after adjusting for confounders. In addition, the RCS analysis suggested a reverse J-shaped relationship between dietary VD intake and PE risk (P-nonlinearity = 0·02). A similar association was also found between serum concentrations of total 25(OH)D and PE risk (P-nonlinearity = 0·02). In conclusion, this study provides evidence that higher dietary intake and serum levels of VD are associated with the lower risk of PE in Chinese pregnant women.

Outbreak of the South American tomato leafminer, Tuta absoluta, in the Chinese mainland: geographic and potential host range expansion.

BACKGROUND: In 2017 Tuta absoluta was identified as an invasive species in China. Due to its rapid geographic expansion and the severe crop damage it causes, T. absoluta poses a serious threat to China's tomato production industry. To determine its geographic distribution and host range, intensive surveys and routine monitoring were conducted across the Chinese mainland between 2018 and 2019. The population colonization coefficient (PCC; ratio of colonized sites and prefectures) and population occurrence index (POI; ratio of infested host species and PCCs) were calculated. RESULTS: In northwestern China, T. absoluta populations established in Xinjiang exhibited a medium PCC value (~0.03). In southwestern China, populations in Yunnan and its five neighboring provinces exhibited high (~0.50 in Yunnan and Guizhou), or low (<0.02 in Guangxi, Sichuan, Hunan, and Chongqing) PCC values. In the Chinese mainland, infestations of four crop plant species (tomato, eggplant, potato, and Chinese lantern) and two wild plant species (black nightshade and Dutch eggplant) were identified; tomatoes were infested in every colonized province. Chinese lantern and Dutch eggplant are potentially novel hosts. Yunnan, Guizhou, and Xinjiang experienced the most serious damage (POI). In southwestern China, observed damage significantly decreased with increased distance from the first discovery site of T. absoluta to the farthest county of an infested province increased. CONCLUSION: T. absoluta populations are well-established and could potentially spread to other regions of China. The present study helps to inform the establishment of better pest management guidelines and strategies in China and tomato-producing regions worldwide. © 2021 Society of Chemical Industry.

The deficiency of FKBP-5 inhibited hepatocellular progression by increasing the infiltration of distinct immune cells and inhibiting obesity-associated gut microbial metabolite.

BACKGROUND: Gut microbiota has a number of essential roles in nutrition metabolism and immune homeostasis, and is closely related to hepatocellular progression. In recent years, studies have also shown that FK506 binding protein 5 (FKBP-5) plays a crucial role in immune regulation. However, it is not yet clear whether FKBP-5 promotes the development of hepatocellular carcinoma (HCC) by affecting immune function and gut microbiota. METHODS: FKBP-5 expression was verified by immunochemistry and western blot and reverse transcription polymerase chain reaction (RT-qPCR) assays. After treatment in WT and FKBP-5-/- mice, the histological characteristic of mice liver tissue was assessed by H&E staining, and hepatic leukocytes and hepatic NKT cells were identified by flow cytometer. Meanwhile, primary bile acids (BAs), secondary BAs, serum total cholesterol, and the weight of abdomen adipose tissues were examined, and the gut microbiota was evaluated by 16S ribosomal ribonucleic acid (rRNA) sequencing. RESULTS: We discovered that FKBP-5 was highly expressed in HCC tissues. Meanwhile, FKBP-5 deletion inhibited tumor progression by increasing CD8+ T, CD4+ T, NKT and CD4+NKT cells in mice after diethylnitrosamine (DEN) injection. Besides, we proved that FKBP-5 deletion generated rapid and significant reductions in the intestinal BAs, the weight of abdomen adipose tissues and the serum total cholesterol. FKBP-5 deletion also led to a change in the composition of gut microbiota, suggesting that BAs are the main dietary factor regulating gut microbiota, which could be affected by FKBP-5 deletion. Further, we uncovered that anti-CD4 and anti-CD8 treatments facilitated hepatocellular progression by modulating gut microbiota composition in FKBP-5-/- mice. CONCLUSIONS: Therefore, we demonstrated that FKBP-5 deletion inhibited hepatocellular progression by modulating immune response and gut microbiome-mediated BAs metabolism.

Investigating the mechanisms of Modified Xiaoyaosan (tiaogan-liqi prescription) in suppressing the progression of atherosclerosis, by means of integrative pharmacology and experimental validation.

Atherosclerosis (AS)-related diseases remain among the leading causes of death worldwide. Modified Xiaoyaosan (also called Tiaogan-Liqi prescription, TGLQ), a traditional Chinese medical formulation, has been widely applied in the treatment of AS-related diseases. The aim of this study was to investigate the underlying pharmacological mechanisms of TGLQ in acting on AS. A total of 548 chemical compounds contained in TGLQ, and 969 putative targets, were collected from the Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine, while 1005 therapeutic targets for the treatment of AS were obtained from the DisGeNET, TTD and CTD databases. Moreover, the 63 key targets were screened by the intersection of the targets above, and by network topological analysis. Further functional enrichment analysis showed that the key targets were significantly associated with regulation of the immune system and inflammation, improvement of lipid and glucose metabolism, regulation of the neuroendocrine system and anti-thrombosis effect. The in vivo experiments confirmed that TGLQ could reduce plasma lipid profiles and plasma inflammatory cytokines, and also inhibit AS plaque formation, within the AS model ApoE-/- mice. The in vitro experiments validated the hypothesis that TGLQ could significantly reduce intracellular lipid accumulation, suppress the production of inflammatory cytokines of macrophages induced by oxidized-LDL, and inhibit the protein expression of heat shock protein 90 and toll-like receptor 4. This study identified a list of key targets of TGLQ in the treatment of AS by applying an integrative pharmacology approach, which was validated by in vivo and in vitro experimentation.

COP9 Signalosome Subunit 3 Restricts Neuroinflammatory Responses During Cerebral Ischemia/Reperfusion Injury Through Stabilizing Suppressor of Cytokine Signaling 3 Protein.

BACKGROUND: The suppressor of cytokine signaling 3 (SOCS3) is a specific negative regulator of signal transducer and activator of transcription 3 (STAT3) signaling, which is predominantly activated to induce neuroinflammatory response in microglia and functions essential roles during cerebral ischemia-reperfusion (I/R) injury. Constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is a signaling platform controlling protein stability by remodeling of cullin-RING ubiquitin ligases, which is recently reported to specifically recognize proteins with SOCS-box domains. However, whether SOCS3 is related to COP9 signalosome in neuroinflammation during cerebral I/R injury is completely unclear. METHODS: Mice subjected to transient middle cerebral artery occlusion (MCAO) and reperfusion, and BV2 microglia cells treated with oxygen-glucose deprivation and reoxygenation (OGD/R) were used to mimic cerebral I/R injury. Western blot, qRTPCR, immunofluorescence, and co-Immunoprecipitation assays were performed to explore the regulatory mechanism of SOCS3 on neuroinflammation and the relationship of SOCS3 and COP9 signalosome during cerebral I/R injury. RESULTS: SOCS3 expression is significantly upregulated in microglia during OGD/R treatment, and overexpression of SOCS3 suppresses OGD/R-induced STAT3 activation and inflammatory factor expression. Furthermore, we find that COP9 signalosome subunit 3 (CSN3) interacts with SOCS3 protein to enhance its stability, thereby resulting in restricting OGD/R-induced STAT3 activation and inflammatory response. Moreover, we find that knockdown of CSN3 evidently accelerates STAT3 activation, and aggravates cerebral I/R injury in vivo. CONCLUSION: CSN3 restricts neuroinflammatory responses during cerebral I/R injury through stabilizing SOCS3 protein and indicates that CSN3 a potential therapeutic target for cerebral I/R injury.

Cyclosporine A relieved proteinuria and hypoproteinemia in DGKE nephropathy.

BACKGROUND: The DGKE gene encodes the diacylglycerol kinase epsilon (DGKε). Loss-of-function mutations of DGKE caused a group of rare renal diseases, which are called DGKE nephropathy. We report the clinical manifestations and therapeutic effects of a patient diagnosed with DGKE nephropathy. CASE REPORT: The patient's initial symptoms were fever, diarrhea, eyelid edema, acute anemia, acute thrombocytopenia, an elevation of plasm D-dimer, proteinuria, microscopic hematuria, without oliguria or renal insufficiency at the age of 7.6 months. Hemolytic uremic syndrome was diagnosed. His proteinuria and hematuria turned out negative 2 months later. Proteinuria was noticed again at the age of 5.5-year old when he was brought to the hospital because of failure to thrive. Since then, he had been noticed with persistent proteinuria. RESULTS: Genetic analysis revealed 2 novel heterozygous mutations on DGKE of the patient. Renal pathology mimicked membrane proliferative glomerulonephritis (MPGN). CONCLUSIONS: After a 5-month treatment of cyclosporine A (CsA), proteinuria and hypoproteinemia have relieved apparently. We also observed an improvement of his growth.