TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE.

Small Transjugular Intrahepatic Portosystemic Shunt Plus Variceal Embolization for Gastric Varices: A Multicenter Cohort Study.

BACKGROUND & AIMS: The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs. METHODS: This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at 7 medical centers. The primary endpoint was all-cause rebleeding, and the secondary endpoints included overt hepatic encephalopathy (OHE) and all-cause mortality. RESULTS: A total of 629 patients were included. Among them, 429 (68.2%) had gastroesophageal varices type 1 (GOV1), 145 (23.1%) had gastroesophageal varices type 2 (GOV2), and 55 (8.7%) had isolated gastric varices type 1 (IGV1). In the entire cohort, adjunctive embolization reduced rebleeding (6.2% vs 13.6%; P = .005) and OHE (31.0% vs 39.4%; P = .02) compared with TIPS alone. However, no significant differences were found in mortality (12.0% vs 9.7%; P = .42). In patients with GOV2 and IGV1, TIPS plus variceal embolization reduced both rebleeding (GOV2: 7.8% vs 25.1%; P = .01; IGV1: 5.6% vs 30.8%; P = .03) and OHE (GOV2: 31.8% vs 51.5%; P = .008; IGV1: 11.6% vs 38.5%; P = .04). However, in patients with GOV1, adjunctive embolization did not reduce rebleeding (5.9% vs 8.7%; P = .37) or OHE (33.1% vs 35.3%; P = .60). CONCLUSIONS: Compared with TIPS alone, 8-mm TIPS plus variceal embolization reduced rebleeding and OHE in patients with GOV2 and IGV1. These findings suggest that patients with GOV2 and IGV1, rather than GOV1, could benefit from embolization with TIPS.

Multi-omics analysis of gut-brain axis reveals novel microbial and neurotransmitter signatures in patients with arteriosclerotic cerebral small vessel disease.

Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.

A systematic review and meta-analysis:comparing the efficacy of the Ilizarov technique alone with lengthening over a nail for lower extremity bone defects.

PURPOSE: The task faced by surgeons becomes significantly more challenging when they encounter lower extremity bone defects due to a variety of causes requiring lengthening. The most discussed and successful approach is the Illizarov technique, or lengthening over a nail (LON):distraction osteogenesis is also widely performed with monoliteral external fixators and intramedullarylengthening nails have increasingly been used in the last decade. METHODS: The data were collected from PubMed, Cochrane Library, Embase, and the Web of Science for all available studies comparing the outcomes of Ilizarov technique alone and LON technique (from January 1, 1997, to November 30, 2023). The outcomes of interest encompassed the external fixation index (EFI) (month/cm), mean duration of follow-up (MFT) (month), length gained (LG) (cm), consolidation index (CIx) (month/cm), and bone healing index (BHI) (month/cm).Complications include pin tract infection rate (PTI), axial deviation rate (AD), occurrence of intramedullary infection (II), delayed consolidation rate (DC), as well as data categorized into three levels of problems, obstacles, and sequelae based on the severity of complications.Two reviewers independently assessed each study for quality and extracted data. The case-control or respective cohort studies were evaluated using the Newcastle-Ottawa scale (NOS) to determine their techniqueological rigor.The Cochrane Collaboration's risk assessment tool was employed to perform quality evaluations for randomized controlled trials. RESULTS: This review included thirteen studies comprising a total of 629 patients.The external fixation index (month/cm) was significantly smaller in the LON technique compared to the Ilizarov technique alone [Mean Difference(MD) = -29.59, 95% CI -39.68--19.49, P < 0.00001].In terms of the mean follow-up time(month) (MD = -0.92, 95% CI -3.49-1.65, P = 0.57), length gained (cm) (MD = -0.87, 95%CI -2.80-1.07, P = 0.38), consolidation index (month/cm) (MD = 0.66, 95% CI -3.44-4.77, P = 0.75), and bone healing index (month/cm) (MD = -3.33, 95% CI -13.07-6.41, P = 0.5), there were no significant differences observed. The LON technique exhibited a lower incidence of axial deviation [Odds Ratio(OR) = 0.06, 95%CI 0.03-0.16, P < 0.00001] and pin tract infection (OR = 0.30, 95%CI 0.18-0.50, P < 0.00001) compared to the Ilizarov technique alone.The remaining complications, such as intramedullary infection rate (OR = 0.93, 95%CI 0.42-2.06, P = 0.85) and delayed consolidation rate(OR = 0.61, 95%CI 0.20-1.86, P = 0.38), did not exhibit statistically significant differences.Our findings demonstrated that the LON technique results in lower incidences of problems (38.5%vs.58.6%) and sequelae (16.6% vs.30.9%) when compared to the Ilizarov technique alone. However, the rates of obstacles (32.4% vs.32.3%) were comparable between the two methods. CONCLUSIONS: Our findings indicate that patients treated with the LON technique experienced significantly shorter external fixation durations and a lower incidence of complications (e.g., pin tract infections and axial deviation) compared to those treated with the Ilizarov technique alone. Other outcome metrics showed no significant differences between the two techniques. However, the LON technique offers substantial benefits, including reduced external fixation times and increased comfort, which enhance patient compliance. In conclusion, the LON technique is a safe, reliable, and effective method for treating tibial and femoral defects.

Phenolic acids from Prunella vulgaris alleviate cardiac remodeling following myocardial infarction partially by suppressing NLRP3 activation.

Acute myocardial infarction (MI) is one of the leading causes of mortality around the world. Prunella vulgaris (Xia-Ku-Cao in Chinese) is used in traditional Chinese medicine practice for the treatment of cardiovascular diseases. However, its active ingredients and mechanisms of action on cardiac remodeling following MI remain unknown. In this study, we investigated the cardioprotective effect of P. vulgaris on MI rat models. MI rats were treated with aqueous extract of P. vulgaris or phenolic acids from P. vulgaris, including caffeic acid, ursolic acid or rosmarinic acid, 1 day after surgery and continued for the following 28 days. Then the cardioprotective effect, such as cardiac function, inflammatory status, and fibrosis areas were evaluated. RNA-sequencing (RNA-seq) analysis, real-time polymerase chain reaction (PCR), western blotting, and ELISA were used to explore the underlying mechanism. In addition, ultra-high performance liquid chromatography/mass spectrometer analysis was used to identify the chemicals from P. vulgaris. THP-1NLRP3-GFP cells were used to confirm the inhibitory effect of P. vulgaris and phenolic acids on the expression and activity of NLRP3. We found that P. vulgaris significantly improved cardiac function and reduced infarct size. Meanwhile, P. vulgaris protected cardiomyocyte against apoptosis, evidenced by increasing the expression of anti-apoptosis protein Bcl-2 in the heart and decreasing lactate dehydrogenase (LDH) levels in serum. Results from RNA-seq revealed that the therapeutic effect of P. vulgaris might relate to NLRP3-mediated inflammatory response. Results from real-time PCR and western blotting confirmed that P. vulgaris suppressed NLRP3 expression in MI heart. We also found that P. vulgaris suppressed NLRP3 expression and the secretion of HMGB1, IL-1ß, and IL-18 in THP-1NLRP3-GFP cells. Further studies indicated that the active components of P. vulgaris were three phenolic acids, those were caffeic acid, ursolic acid, and rosmarinic acid. These phenolic acids inhibited LPS-induced NLRP3 expression and activity in THP-1 cells, and improved cardiac function, suppressed inflammatory aggregation and fibrosis in MI rat models. In conclusion, our study demonstrated that P. vulgaris and phenolic acids from P. vulgaris, including caffeic acid, ursolic acid, and rosmarinic acid, could improve cardiac function and protect cardiomyocytes from ischemia injury during MI. The mechanism was partially related to inhibiting NLRP3 activation.

FOXP2 suppresses the proliferation, invasion, and aerobic glycolysis of hepatocellular carcinoma cells by regulating the KDM5A/FBP1 axis.

The Warburg effect is the preference of cancer cells to use glycolysis rather than oxidative phosphorylation to generate energy. Accumulating evidence suggests that aerobic glycolysis is widespread in hepatocellular carcinoma (HCC) and closely related to tumorigenesis. The purpose of this study was to investigate the role and mechanism of forkhead box P2 (FOXP2) in aerobic glycolysis and tumorigenesis in HCC. Here, we found that FOXP2 was lower expressed in HCC tissues and cells than in nontumor tissues and normal hepatocytes. Overexpression of FOXP2 suppressed cell proliferation and invasion of HCC cells and promoted cell apoptosis in vitro, and hindered the growth of mouse xenograft tumors in vivo. Further researches showed that FOXP2 inhibited the Warburg effect in HCC cells. Moreover, we demonstrated that FOXP2 up-regulated the expression of fructose-1, 6-diphosphatase (FBP1), and the inhibitory effect of FOXP2 on glycolysis was dependent on FBP1. Mechanistically, as a transcription factor, FOXP2 negatively regulated the transcription of lysine-specific demethylase 5A (KDM5A), and then blocked KDM5A-induced H3K4me3 demethylation in FBP1 promoter region, thereby promoting the expression of FBP1. Consistently, overexpressing KDM5A or silencing FBP1 effectively reversed the inhibitory effect of FOXP2 on HCC progression. Together, our findings revealed the mechanistic role of the FOXP2/KDM5A/FBP1 axis in glycolysis and malignant progression of HCC cells, providing a potential molecular target for the therapy of HCC.

Liver Injury in Patients with COVID-19: A Retrospective Study.

Objectives: The objective of this study is to explore the incidence, characteristics, risk factors, and prognosis of liver injury in patients with COVID-19. Methods: We collected clinical data of 384 cases of COVID-19 and retrospectively analyzed the incidence, characteristics, and risk factors of liver injury of the patients. In addition, we followed the patient two months after discharge. Results: A total of 23.7% of the patients with COVID-19 had liver injury, with higher serum AST (P < 0.001), ALT (P < 0.001), ALP (P = 0.004), GGT (P < 0.001), total bilirubin (P = 0.002), indirect bilirubin (P = 0.025) and direct bilirubin (P < 0.001) than the control group. The median serum AST and ALT of COVID-19 patients with liver injury were mildly elevated. Risk factors of liver injury in COVID-19 patients were age (P = 0.001), history of liver diseases (P = 0.002), alcoholic abuse (P = 0.036), body mass index (P = 0.037), severity of COVID-19 (P < 0.001), C-reactive protein (P < 0.001), erythrocyte sedimentation rate (P < 0.001), Qing-Fei-Pai-Du-Tang treatment (P = 0.032), mechanical ventilation (P < 0.001), and ICU admission (P < 0.001). Most of the patients (92.3%) with liver injury were treated with hepatoprotective drugs. 95.6% of the patients returned to normal liver function tests at 2 months after discharge. Conclusions: Liver injury was commen in COVID-19 patients with risk factors, most of them have mild elevations in transaminases, and conservative treatment has a good short-term prognosis.

Discovery of Salidroside as a Novel Non-Coding RNA Modulator to Delay Cellular Senescence and Promote BK-Dependent Apoptosis in Cerebrovascular Smooth Muscle Cells of Simulated Microgravity Rats.

Cardiovascular aging has been reported to accelerate in spaceflights, which is a great potential risk to astronauts' health and performance. However, current exercise routines are not sufficient to reverse the adverse effects of microgravity exposure. Recently, salidroside (SAL), a valuable medicinal herb, has been demonstrated to display an important role for prevention and treatment in cardiovascular and other diseases. In the present work, Sprague-Dawley rats with four-week tail-suspension hindlimb-unloading were used to simulate microgravity effects on the cardiovascular system. We found that intragastrical administration of SAL not only significantly decreased the expressions of senescence biomarkers, such as P65 and P16, but also obviously increased the expressions of BK-dependent apoptotic genes, including the large-conductance calcium-activated K+ channel (BK), Bax, Bcl-2, and cleaved caspase-3, in vascular smooth muscle cells (VSMCs) in vivo and in vitro. In addition, relative non-coding RNAs were screened, and a luciferase assay identified that SAL increased apoptosis by activating LncRNA-FLORPAR, inhibiting miR-193, and then triggering the activity of the BK-α subunit. Our work indicated that SAL is a novel non-coding RNA modulator for regulating the LncRNA-FLORPAR sponging miR-193 pathway, which significantly promoted BK-dependent apoptosis and delayed cerebrovascular aging-like remodeling during simulated microgravity exposure. Our findings may provide a new approach to prevent cardiovascular aging in future spaceflights.

MicroRNA-455-3p functions as a tumor suppressor by targeting HDAC2 to regulate cell cycle in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers. MicroRNA has been studied more and more deeply and may become a new target for the treatment of HCC. Here, we investigated the role of miR-455-3p in HCC progression. Compared with non-tumor tissues and normal human hepatic cells, miR-455-3p expression was significantly downregulated in HCC tissues and cell lines. And overexpression of miR-455-3p inhibited cell proliferation and migration but promoted cell apoptosis in HCC cell lines HepG2 and Huh7. Mechanism studies displayed that miR-455-3p targeted HDAC2 and negatively regulated HDAC2 expression. Moreover, HDAC2 was highly expressed in HCC tissues and cell lines. Overexpression of HDAC2 reversed the inhibitory effects of miR-455-3p on cell proliferation, migration and cell cycle protein (CDK6 and cyclin D1) expression, and neutralized the promotion effects of miR-455-3p on cell apoptosis and the activation of p53 pathway. Furthermore, a p53 inhibitor Pifithrin-α (PFT-α) effectively abolished the effects of miR-455-3p on HCC cell behaviors. Additionally, the role of miR-455-3p in tumorigenesis was evaluated by using a mouse xenograft model, and the data showed that miR-455-3p suppressed tumor growth in vivo. In summary, our results suggested that miR-455-3p targeted HDAC2 to inhibit cell proliferation, migration and promote cell apoptosis via the activation of p53 pathway.

The long noncoding RNA OTUD6B-AS1 enhances cell proliferation and the invasion of hepatocellular carcinoma cells through modulating GSKIP/Wnt/ß-catenin signalling via the sequestration of miR-664b-3p.

Ovarian tumour domain containing 6B antisense RNA1 (OTUD6B-AS1), a newly identified long noncoding RNA (lncRNA), has been reported as a key cancer-related lncRNA. However, the detailed relevance of OTUD6B-AS1 in hepatocellular carcinoma (HCC) remains undetermined. This study was designed to determine the functional significance and regulatory mechanism of OTUD6B-AS1 in HCC. We found that the expression of OTUD6B-AS1 was up-regulated in HCC tissues, and patients with high levels of OTUD6B-AS1 expression had shorter survival rates than those with low OTUD6B-AS1 expression. Elevated expression of the lncRNA was also found in multiple HCC cell lines and the silencing of OTUD6B-AS1 significantly decreased proliferation, colony formation and invasion. Correspondingly, OTUD6B-AS1 overexpression had the opposite effect on HCC cell invasion, colony formation and proliferation. Notably, OTUD6B-AS1 was identified as a molecular sponge of microRNA-664b-3p (miR-664b-3p). The down-regulation of miR-664b-3p was detected in HCC tissues and cell lines, and the up-regulation of miR-664b-3p repressed proliferation and invasion in HCC cells by targeting the glycogen synthase kinase-3ß interaction protein (GSKIP). Moreover, OTUD6B-AS1 knockdown or miR-664b-3p up-regulation exerted a suppressive effect on Wnt/ß-catenin signalling via the down-regulation of GSKIP. In addition, GSKIP overexpression markedly reversed OTUD6B-AS1 knockdown- or miR-664b-3p overexpression-induced antitumour effects in HCC. Further data confirmed that OTUD6B-AS1 knockdown exerted a tumour-inhibition role in HCC in vivo. Overall, these findings indicate that the lncRNA OTUD6B-AS1 accelerates the proliferation and invasion of HCC cells by enhancing GSKIP/Wnt/ß-catenin signalling via the sequestration of miR-664b-3p. Our study reveals a novel molecular mechanism, mediated by lncRNA OTUD6B-AS1, which may play a key role in regulating the progression of HCC.

HIPK3 Circular RNA Promotes Metastases of HCC Through Sponging miR-338-3p to Induce ZEB2 Expression.

BACKGROUND: Upregulation of circHIPK3 has been observed in several kinds of malignancies. However, the mechanisms of circHIPK3 in HCC metastases remains unclear. We investigated the role and the mechanisms of circHIPK3 in the development of HCC. METHODS: HCC tissues and paired adjacent non-tumor tissues of surgical patients were used to evaluate circHIPK3 expression. A series of biological experiments had been taken to evaluate the pro-metastatic ability of circHIPK3 during HCC development in vitro and in vivo. The potential mechanisms of circHIPK3 in HCC development were identified by RT-qPCR, Western blot, RIP, and luciferase reporter assays. RESULTS: CircHIPK3 expression is significantly upregulated during HCC development. Overexpression of circHIPK3 promotes cell migration, invasion, and metastases in vitro and in vivo. CircHIPK3 promoted HCC metastases by sponging miR-338-3p to regulate EMT-associated proteins E-cadherin, vimentin, and ZEB2 expression. CONCLUSION: CircHIPK3 plays a regulatory role in metastatic HCC by sponging miR-338-3p to induce ZEB2 expression, thus promoting EMT procession.

Association of CD14 gene -260C>T and -561C>T polymorphisms with cancer susceptibility: A meta-analysis.

BACKGROUND: Two polymorphisms, -260C>T (rs2569190) and -561C>T (rs5744455), in the CD14 gene have been implicated in susceptibility to cancer. However, the results remain inconclusive. The current meta-analysis was carried out aiming to confirm the function of these two polymorphisms on the susceptibility of cancer. METHODS: We collected eligible studies from databases, including PubMed, EMBASE, CNKI, Wanfang, and VIP (Weipu). We used logistic regression calculation to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After strict selection, 24 studies with 5854 cases and 10339 controls for -260C>T and seven studies with 1809 cases and 7289 controls for -561C>T were finally enlisted into our analysis reference material. Pool results revealed that neither -260C>T, nor -561C>T was found to have any association with overall cancer susceptibility. Nevertheless, when stratified by cancer type, we detected a decreased risk associated with other cancers in a heterozygous model (OR = 0.69, 95% CI = 0.51-0.93, p = 0.014) and a dominant model (OR = 0.70, 95% CI = 0.53-0.93, p = 0.012) for -561C>T. An increased risk was found in other cancers under an allele model (OR = 1.29, 95% CI = 1.03-1.62, p = 0.026), in laryngeal cancer under a dominant model (OR = 1.38, 95% CI = 1.11-1.71, p = 0.003) and for a score ≤ 9 under a recessive model (OR = 1.45, 95% CI = 1.09-1.91, p = 0.009) for -561C>T. CONCLUSIONS: In the present study, we conclude that the CD14 -260C>T and -561C>T polymorphisms might not be associated with overall cancer risk. Further studies are encouraged to confirm this conclusion.

ATDC promotes the growth and invasion of hepatocellular carcinoma cells by modulating GSK-3ß/Wnt/ß-catenin signalling.

Accumulating evidence has suggested that the ataxia telangiectasia group D complementing (ATDC) gene is an emerging cancer-related gene in multiple human cancer types. However, little is known about the role of ATDC in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the expression level, biological function and underlying mechanism of ATDC in HCC. The expression of ATDC in HCC cells was detected by quantitative real-time polymerase chain reaction and western blot analysis. Cell growth was determined by cell counting kit-8 assay and colony formation assay. Cell invasion was assessed by Transwell invasion assay. The activation status of Wnt/ß-catenin signalling was evaluated by the luciferase reporter assay. Functional experiments showed that the silencing of ATDC expression significantly suppressed the growth and invasion of HCC cells, whereas the overexpression of ATDC promoted the growth and invasion of HCC cells in vitro. Moreover, we showed that ATDC overexpression promoted the phosphorylation of glycogen synthase kinase (GSK)-3ß and resulted in the activation of Wnt/ß-catenin signalling. Notably, the inhibition of GSK-3ß activity significantly abrogated the tumour suppressive effect of ATDC silencing, while the silencing of ß-catenin partially reversed the oncogenic effect of ATDC overexpression. Taken together, these findings reveal an oncogenic role of ATDC in HCC and show that the suppression of ATDC impedes the growth and invasion of HCC cells associated with the inactivation of Wnt/ß-catenin signalling. Our study suggests that ATDC may serve as a potential therapeutic target for HCC.

Roles of T-cell Immunoglobulin and Mucin Domain Genes and Toll-like Receptors in Wheezy Children with Mycoplasma pneumoniae Pneumonia.

BACKGROUND: The study aimed to explore possible factors influencing wheezing in children with Mycoplasma pneumoniae pneumonia (MPP). METHODS: The study included 84 children with MPP, who were divided into two groups: wheezy group (n=40) and non-wheezy group (n=44), along with 30 age-matched healthy controls. T-cell immunoglobulin and mucin domain gene (Tim) 1, 3 and Toll-like receptor (TLR) 2, 4 were evaluated using RT-PCR. Serum IL-10, TNF-α, IFN-γ and IgE were assessed by enzyme-linked immunosorbent assay. Peripheral blood eosinophil (EOS) was measured by an automated haematology. RESULTS: Children with MPP had markedly increased TLR2, TLR4, Tim1, IL-10, TNF-α, IgE and EOS, and decreased IFN-γ than the healthy controls. In the presence of MPP, wheezy children had significantly elevated TLR2, Tim1, Tim3, TNF-α, IgE and EOS than non-wheezy children. In wheezy children with MPP, MP-specific antibody titre was positively correlated with TLR2 and TIM1, and negatively correlated with IFN-γ. IgE was positively correlated with TLR2, TLR4 and Tim1, while EOS was positively correlated with Tim1 and Tim3. CONCLUSION: TLR2, Tim1, Tim3, TNF-α, IgE and EOS play a role in MPP-related wheezing in children. The role of IgE might be associated with TLR2 and Tim1, and the role of EOS might be associated with Tim1 and Tim3.

Pathogenesis and association of Mycoplasma pneumoniae infection with cardiac and hepatic damage.

The aim of this study was to investigate the pathogenesis of Mycoplasma pneumoniae (MP) infection and its association with cardiac and hepatic damage. Between March 2013 and March 2014, 59 children with MP pneumonia (MPP) and 30 healthy children were enrolled. Serum titers of TLR4, T cell immunoglobulin and mucin-domain (TIM) 3, IL-10, TNF-α, and IFN-γ were measured both in children with MPP and healthy children. Additionally, MP-specific antibody titer and creatine kinase-MB (CK-MB), and alanine transaminase (ALT) titers were measured in patients with MPP. There were significant differences between the MPP patients and healthy controls in titers of TIM1 (P < 0.01), TLR2 (P = 0.028), TLR4 (P = 0.019), IL-10 (P < 0.01), TNF-α (P < 0.01) and IFN-γ (P < 0.01); however, no significant difference was found in TIM3 titers (P = 0.8181). TIM1 was correlated with CK-MB (P = 0.025), whereas both TIM1 and TLR2 titers were correlated with MP-specific antibody titers (P < 0.001; P = 0.003, respectively). Additionally, there were correlations between ALT, TIM3, and TLR2 titers (P = 0.025; P = 0.037, respectively). The titers of TIM1 were significantly higher in patients with cardiac damage (P = 0.007) than in those without it, whereas the titers of TLR2 were significantly higher in patients with hepatic damage (P = 0.026) than in those without it. TLR2, TLR4 and TIM1 may be involved in the process of MP infection. Additionally, TLR2, TLR4, TIM1 and TIM3 may play particular roles in the pathogenesis of MPP-associated cardiac and hepatic damage.

Activation of α7nAChR by nicotine reduced the Th17 response in CD4(+)T lymphocytes.

BACKGROUND: nAChRs play an important role in the regulation and modulation of immune cell proliferation, differentiation, migration and cell-cell interactions. The present study was to characterize the expression of α7nAChR on human peripheral blood mononuclear cells (hPBMC) and CD4(+)T lymphocytes, and to explore the change of Th17 expression after activation of α7nAChR on human CD4(+)T lymphocytes. METHODS: A Ficoll gradient was used to separate hPBMC from whole blood, and then CD4(+)T lymphocytes were isolated by magnetic bead separation. The expression of α7nAChR on PBMC and CD4(+)T lymphocytes was analyzed using flow cytometry before and after stimulation with phytohemagglutinin (PHA). The effect of α7nAChR stimulation by nicotine or inhibition by α-bungarotoxin (α-BTX), as well as Th17 expression on the phenotype of CD4(+)T cells was evaluated using flow cytometric analysis. RESULTS: The percentage of CD4(+)T cells in reduced PBMC, while the expression of α7nAChR increased when cells were stimulated by nicotine. This effect vanished when co-treated with nicotine and α-BTX. α7nAChR was found to expressed in about 90% of CD4(+)T cells. However, α7nAChR expression reduced to 80% on CD4(+)T cells after stimulation with PHA for 24 h. Stimulation of α7nAChR with nicotine increased the expression of Th17 cells, and this upregulation reduced when AChRα7 was inhibited by α-BTX. CONCLUSION: α7nAChR was ubiquitously expressed by CD4(+)T lymphocytes, which was correlated with the cell activation status. Meanwhile, activation of nAChRα7 by nicotine in CD4 cells reduced the Th17 response.

A meta-analysis of IL-13 polymorphisms and pediatric asthma risk.

BACKGROUND: IL13-1112C/T and +2044A/G polymorphisms have been reported to be correlated with pediatric asthma susceptibility, but study results were still debatable. Thus, a meta-analysis was conducted. MATERIAL/METHODS: PubMed and EMBASE databases were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association in the random-effects model or fixed-effects model. RESULTS: Fourteen case-control studies with 4710 asthma cases and 6086 controls were included in this meta-analysis. IL13-1112C/T and +2044A/G polymorphisms were significantly associated with an increased risk of pediatric asthma (OR=1.14, 95% CI 1.01-1.28, P=0.04, I2=0%; OR=1.20, 95% CI 1.09-1.32, P<0.01, I2=0%), respectively. In the subgroup analysis by ethnicity, IL13-1112C/T polymorphism was significantly associated with pediatric asthma risk in whites (OR=1.29, 95% CI 1.02-1.63, P=0.03, I2=16%). IL13 +2044A/G polymorphism was significantly associated with pediatric asthma risk in Asians (OR=1.21, 95% CI 1.10-1.34, P<0.01, I2=24%). CONCLUSIONS: The results of this meta-analysis suggest that IL13-1112C/T and +2044A/G polymorphisms contribute to the development of pediatric asthma.

Ferrate(VI)-based oxidation for ultrafiltration membrane fouling mitigation in shale gas produced water pretreatment: Role of high-valent iron intermediates and hydroxyl radicals.

Ultrafiltration (UF) is increasingly used in the pretreatment of shale gas produced water (SGPW), whereas severe membrane fouling hampers its actual operation. In this work, ferrate(VI)-based oxidation was proposed for membrane fouling alleviation in SGPW pretreatment, and the activation strategies of calcium peroxide (CaO2) and ultraviolet (UV) were selected for comparison. The findings indicated that UV/Fe(VI) was more effective in removing fluorescent components, and the concentration of dissolved organic carbon was reduced by 24.1 %. With pretreatments of CaO2/Fe(VI) and UV/Fe(VI), the terminal specific membrane flux was elevated from 0.196 to 0.385 and 0.512, and the total fouling resistance diminished by 52.7 % and 76.2 %, respectively. Interfacial free energy analysis indicated that the repulsive interactions between pollutants and membrane were notably enhanced by Fe(VI)-based oxidation, thereby delaying the deposition of cake layers on the membrane surface. Quenching and probe experiments revealed that high-valent iron intermediates (Fe(IV)/Fe(V)) played significant roles in both CaO2/Fe(VI) and UV/Fe(VI) processes. Besides, hydroxyl radicals (•OH) were also important reactive species in the UV/Fe(VI) treatment, and the synergistic effect of Fe(IV)/Fe(V) and •OH showed a positive influence on SGPW fouling mitigation. In general, these findings establish a theoretical underpinning for the application of Fe(VI)-based oxidation for UF membrane fouling mitigation in SGPW pretreatment.

Protective effect of naringin against radiation-induced heart disease in rats via Sirt1/NF-κB signaling pathway and endoplasmic reticulum stress.

This study was designed to explore the protective effect and mechanism of naringin (NG) on radiation-induced heart disease (RIHD) in rats. Rats were divided into four x-ray (XR) irradiation groups with different absorbed doses (0/10/15/20 Gy), or into three groups (control, XR, and XR + NG groups). Subsequently, the ultrasonic diagnostic apparatus was adopted to assess and compare the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular internal diameter at end diastole (LVIDd), and left ventricular internal diameter at end systole (LVIDs) in rats. Hematoxylin-eosin (H&E) staining and Masson staining were applied to detect the pathological damage and fibrosis of heart tissue. Western blot was used to measure the expression levels of myocardial fibrosis-related proteins, endoplasmic reticulum stress-related proteins, and Sirt1 (silent information regulator 1)/NF-κB (nuclear factor kappa-B) signaling pathway-related proteins in cardiac tissues. Additionally, enzyme-linked immunosorbent assay was utilized to detect the activities of pro-inflammatory cytokines, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in cardiac tissue. The results showed that NG treatment significantly attenuated the 20 Gy XR-induced decline of LVEF and LVFS and the elevation of LVIDs. Cardiac tissue damage and fibrosis caused by 20 Gy XR were significant improved after NG treatment. Meanwhile, in rats irradiated by XR, marked downregulation was identified in the expressions of fibrosis-related proteins (Col I, collagen type I; α-SMA, α-smooth muscle actin; and TGF-ß1, transforming growth factor-beta 1) and endoplasmic reticulum stress-related proteins (GRP78, glucose regulatory protein 78; CHOP, C/EBP homologous protein; ATF6, activating transcription factor 6; and caspase 12) after NG treatment. Moreover, NG treatment also inhibited the production of pro-inflammatory cytokines [interleukin-6, interleukin-1ß, and monocyte chemoattractant protein-1 (MCP-1)], reduced the expression of MDA, and promoted the activities of SOD and CAT. Also, NG treatment promoted Sirt1 expression and inhibited p65 phosphorylation. Collectively, XR irradiation induced cardiac injury in rats in a dose-dependent manner. NG could improve the cardiac injury induced by XR irradiation by inhibiting endoplasmic reticulum stress and activating Sirt1/NF-κB signaling pathway.

Nano-confined catalysis with Co nanoparticles-encapsulated carbon nanotubes for enhanced peroxymonosulfate oxidation in secondary effluent treatment: Water quality improvement and membrane fouling alleviation.

Despite widespread deployment and investigation of ultrafiltration (UF) for secondary effluent purification, the challenge of membrane fouling due to effluent organic matter (EfOM) remains formidable. This study introduced a novel pretreatment method utilizing Co nanoparticles-encapsulated carbon nanotubes activated peroxymonosulfate (Co@CNT/PMS) to degrade EfOM and mitigate membrane fouling. Characterization of Co@CNT revealed the efficient encapsulation of Co nanoparticles within nanotubes, which notably enhanced the catalytic degradation of bisphenol A and typical organics. The tube-encapsulated structure increased the concentration of reactive species within the confined nanoscopic space, thereby improving the probability of collisions with pollutants and promoting their degradation. The Co@CNT/PMS pretreatment led to substantial reductions in aromatic compounds, fluorescent components, and both high and middle molecular weight substances. These changes proved crucial in diminishing the fouling potential in subsequent UF processes, where reversible and irreversible fouling resistances decreased by 97.1 % and 72.8 %, respectively. The transition volume from pore blocking to cake filtration markedly increased, prolonging the formation of a dense fouling layer. Surface properties analysis indicated a significant reduction of pollutants on membrane surfaces after the Co@CNT/PMS pretreatment. This study underscored the efficacy of confinement-based advanced oxidization pretreatment in enhancing UF performance, presenting a viable resolution to membrane fouling.