METTL5: A Potential Biomarker for Nonsmall Cell Lung Cancer That Promotes Cancer Cell Proliferation by Interacting with IGF2BP3.

Objective: To examine if METTL5 promotes the proliferation of nonsmall cell lung cancer (NSCLC) cells by interacting with IGF2BP3. Methods: The expression patterns of METTL5 and IGF2BP3 in NSCLC tissues, their relationship with survival rate, and their correlation were analyzed using bioinformatics and clinical sample analyses. The effects of METTL5 overexpression and IGF2BP3 knockdown, as well as those of METTL5 knockdown and IGF2BP3 overexpression, on the proliferation of NSCLC cells were analyzed by transfecting appropriate constructs. The interaction between METTL5 and IGF2BP3 was verified using the co-immunoprecipitation (Co-IP) assay. The in vivo effects of METTL5 and IGF2BP3 on NSCLC growth were analyzed using the tumor-bearing nude mouse model. Results: METTL5 and IGF2BP3 expression levels were positively correlated and were associated with poor clinical prognosis. The METTL5 and IGF2BP3 expression levels were upregulated in the clinical NSCLC samples. IGF2BP3 expression did not affect METTL5 expression but was regulated by METTL5. IGF2BP3 overexpression mitigated the METTL5 knockdown-induced impaired cell proliferation. Meanwhile, IGF2BP3 knockdown suppressed METTL5-mediated NSCLC cell proliferation. The Co-IP assay results revealed the interaction between METTL5 and IGF2BP3 in NSCLC cells. IGF2BP3 knockdown suppressed tumor growth, whereas IGF2BP3 overexpression enhanced tumor volume and quality. Conclusion: METTL5 induces NSCLC cell proliferation by interacting with IGF2BP3. Thus, METTL5 is a potential biomarker and a therapeutic target for NSCLC.

Consent and Educational Sensitive Exams on Anesthetized Patients: Experiences of Medical Students Across Canada.

OBJECTIVES: This study investigates experiences of medical students across Canada related to consent for educational sensitive (i.e., pelvic, rectal) exams under anesthesia (EUAs). METHODS: A bilingual online questionnaire was developed and distributed to medical students across Canada. RESULTS: Of 134 respondents, 63% had performed a pelvic EUA, 35% a rectal EUA, and 11% another sensitive EUA during their training. For those who had performed pelvic EUA, 28% were unsure if consent had taken place, 26% reported no specific consent, 20% reported specific consent, and 25% had mixed experiences of consent. For rectal EUAs, 48% reported no specific consent, 37% were unsure if consent had taken place, 13% reported that there had been specific consent, and 2% reported mixed experiences. Most respondents were uncomfortable (36%) or not sure if they were comfortable (32%) with how the consent process was handled for student pelvic EUAs; 31% were comfortable. In open-ended responses, respondents described experiences related to variability, discomfort, and authority. CONCLUSIONS: Non-consensual educational sensitive EUAs continue to take place in medical training across Canada, although practices of consent are highly variable. The majority of respondents reported being uncomfortable or unsure if they were comfortable with how consent for educational sensitive EUAs was practised during their training, and some respondents struggled to express their discomfort given the power dynamics at play.

Therapeutic effects of vitamin D supplementation on COVID-19 aggravation: a systematic review and meta-analysis of randomized controlled trials.

Background: The therapeutic effects of vitamin D supplementation on Coronavirus disease 2019 (COVID-19) aggravation remain controversial and inconclusive. To probe into this contentious issue, we performed the present meta-analysis of randomized controlled trials (RCTs). Methods: Literature published up to June 2023 was retrieved from Cochrane Library, PubMed, Web of Science and Embase. RCTs assessing mortality, intensive care unit (ICU) admission, mechanical ventilation (MV), length of hospitalization (LOH), and inflammatory markers containing C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), lactate dehydrogenase (LDH) were included. 19 RCTs were involved in the analysis and were conducted subgroup analyses on the baseline COVID-19 severity and vitamin D administration. Results: In the severity subgroup, statistically significant effects in moderate to severe group were observed in ICU admission (OR 0.43, 95% CI 0.23, 0.80; p = 0.008), MV (OR 0.44, 95% CI 0.27, 0.72; p = 0.001) and LOH (SMD -0.49, 95% CI -0.92, -0.06; p = 0.027). In the administration subgroup, effects of ICU admission (OR 0.39, 95% CI 0.16, 0.97; p = 0.044), MV (OR 0.18, 95% CI 0.07, 0.46; p = 0.000) and LOH (SMD -0.50, 95% CI -0.96, -0.04; p = 0.034) were more pronounced in patients supplied with multiple-dose vitamin D than single-dose. Although the result of mortality showed no statistically significant effect, it indicated a reduced trend (OR 0.87, 95% CI 0.63, 1.12; p > 0.05). The results of inflammatory markers reached no statistical differences. Conclusion: This meta-analysis revealed that moderate to severe COVID-19 patients supplied with multiple doses of vitamin D were less apt to need ICU admission, mechanical ventilation and have shorter hospital stays.

Immunopotentiating effect of lentinan on chicks and its inhibitory effect on Marek's disease virus infection.

Marek's disease virus (MDV) is a significant tumorigenic virus that causes severe immunosuppression in chickens. Lentinan (LNT) is an immunomodulator containing ß-glucans and is widely used in areas such as antiviral, anticancer, and immune regulation. To investigate the immunomodulatory effects of LNT on specific pathogen-free (SPF) chicks and its potential to inhibit MDV infection, we conducted an MDV challenge experiment and observed the immune-enhancing effect of LNT on SPF chicks. The results showed that LNT promoted the growth and development of SPF chicks and induced the upregulation of cytokines such as Mx protein, interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The specific gravity of CD4+ T-lymphocytes and CD8+ T-lymphocytes and their ratios were also significantly upregulated. Prophylactic use of LNT inhibited MDV replication in lymphocytes, liver, and spleen. It also alleviated MDV-induced weight loss and hepatosplenomegaly in SPF chicks. The present study confirms that LNT can enhance the levels of innate and cellular immunity in SPF chicks and contributes to the inhibition of MDV replication in vivo and mitigation of immune organ damage in chicks due to MDV infection. This provides an adjunctive measure for better control of MDV infection.

The causality between obstructive sleep apnea and ventricular structure and function: a bidirectional Mendelian randomization study.

Background: Multiple observational studies have discovered a substantial link between obstructive sleep apnea (OSA) and ventricular dysfunction. However, conventional observational studies are vulnerable to causal reversal and confounding, making it challenging to infer the causes of effects and their direction. Methods: With the help of a bidirectional, two-sample Mendelian randomization (MR) study, we assessed the potential causality between OSA and left and right ventricular (LV, RV) structure and function. We conducted our analysis utilizing summary data from genome-wide association studies of OSA (16,761 cases and 201,194 controls) in the FinnGen Study, as well as LV (36,041 participants) and RV (29,506 participants) in the UK Biobank cardiovascular magnetic resonance research. The inverse variance weighted (IVW) was selected as the main strategy, with the MR-Egger and weighted median methods serving as supplements. Other methods were employed as sensitivity analysis tools to look at heterogeneity and pleiotropy, including MR-Egger intercept, Cochran Q statistic, MR-PRESSO, and leave-one-out analysis. Results: In the primary IVW analysis, genetically predicted OSA was strongly causative on LV end-diastolic volume (ß = 0.114, 95% CI = 0.034-0.194, p = 0.006) and LV stroke volume (ß = 0.111, 95% CI = 0.031-0.191, p = 0.007), and genetically predicted LV ejection fraction was linked to an increased risk of OSA (OR = 1.161, 95% CI = 1.029-1.309, p = 0.015). However, there was no connection found between OSA and any RV parameters. Conclusion: Our genetic analysis raises a potential causative link between OSA and ventricular structure and function, which may improve the knowledge of OSA as a risk factor for cardiovascular disease by demonstrating a direct impact on cardiac structure and function.

HPV prevalence and genotype distribution among 38 056 women in Weifang, China: a cross-sectional study.

OBJECTIVES: Human papillomavirus (HPV) infection is closely associated with cervical cancer, especially the persistent infection of high-risk HPV (HR-HPV) genotypes. Therefore, investigating the HPV prevalence, age-specific, genotype distribution and the impact of the COVID-19 pandemic among large populations was essential for HPV screening and optimising vaccination. DESIGN: This was a cross-sectional study. METHODS: A total of 38 056 cervical epithelial cell specimens were collected in Weifang city from January 2018 to December 2022. The study was divided into seven age groups based on the age of the participants. HPV genotype testing was performed by using a commercial kit which is designed for the detection of 23 HPV genotypes. RESULT: A total of 8998 women were infected with HPV, with an overall positive rate of 23.64% (8998/38 056). Single infection of HPV was dominant among different age groups, which accounted for 71.33% of total infections. The most prevalent genotype was HR-HPV 16 (4.33%), followed by 52, 58, 53 and 68. Low-risk HPV (LR-HPV) 42 exhibited the highest prevalence (2.19%) among six LR-HPV genotypes, representing a novel finding. There was a significant difference in the prevalence across different age groups (p<0.01), with the highest prevalence in the group under 25 years old. During the 3 year COVID-19 breakout period, the number of HPV samples received in 2020, 2021 and 2022 was reduced by 24.03%, 14.79% and 24.76%, respectively. In 2018-2022, the annual prevalence varied between 21.09% and 25.30%, with a decreasing trend, while the prevalence of HR-HPV 39, 56, 31 and LR-HPV 42 increased. CONCLUSION: This study indicates a high-HPV infection rate and age-specific distribution characteristics of HPV genotype infections, as well as analyses of the impact of the COVID-19 outbreak on the HPV prevalence, which provides an epidemiological basis for the control and prevention of HPV infection in this region.

Combined inhibitory effect of interferon and antiserum on avian hepatitis E virus.

Epidemiologic investigations in recent years have shown that the detection rate of avian hepatitis E virus (HEV) in chicken flocks is increasing in China. Nevertheless, effective prevention and control measures are still lacking. In this study, specific pathogen-free (SPF) chicken serum against HEV was prepared using recombinant HEV open reading frames (ORF2 and ORF3) proteins as immunogens. An SPF chicken infection model was established by intravenous inoculation of chick embryos. Swab samples were collected at 7, 14, 21, and 28 d of age and used to detect avian HEV load, along with other indicators, by fluorescence quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) assay. The therapeutic effects on blocking vertical HEV transmission were observed, by using the methods of antibody application alone, mixed, or combined application of each of the 2 antibodies with type I interferon. The results showed that type I interferon alone or in combination with antiserum reduced the positive rate of HEV from 100 to 62.5% and 25%, respectively. However, the avian HEV-positivity rate was reduced to 75, 50, and 37.5% after type I interferon was used alone or in combination with antisera against ORF2 and ORF3, respectively. The inhibitory effect of type I interferon alone or in combination with an antiserum, on HEV replication was more significant in cells than in vivo. In this study, the inhibitory effect of type I interferon alone or in combination with an antiserum on avian HEV replication was observed in vitro and in vivo, providing the necessary technical reserve for disease prevention and control.

A novel electrocoagulation process with centrifugal electrodes for wastewater treatment: Electrochemical behavior of anode and kinetics of heavy metal removal.

Anodic passivation is a key problem to impair the efficiency of in the electrocoagulation (EC) process. Process intensification of EC has attracted increasingly greater attention. In this work, a novel centrifugal electrode reactor was designed and applied in EC process to enhance the treatment of simulated heavy metal wastewater using aluminum anode. Results showed that the removal efficiency of heavy metals was significantly improved by the centrifugal electrodes, compared with the stationary electrodes. Electrochemical behavior of centrifugal electrodes was analyzed by an improved rotating disk electrode system. Anodic polarization behavior of aluminium showed a typical characteristic of dissolution in centrifugal electrodes, rather than passivation in static condition. Anode dissolution was controlled by the diffusion of Cl- ion that was enhanced by centrifugal electrodes. Thus, anode passivation was reduced. In addition, the kinetics analysis indicated that the removal of heavy metals in EC by centrifugal electrodes conformed to Variable-Order-Kinetic (VOK) model based on the Langmuir adsorption.

Non-coding RNAs in cancer therapy-induced cardiotoxicity: Mechanisms, biomarkers, and treatments.

As a result of ongoing breakthroughs in cancer therapy, cancer patients' survival rates have grown considerably. However, cardiotoxicity has emerged as the most dangerous toxic side effect of cancer treatment, negatively impacting cancer patients' prognosis. In recent years, the link between non-coding RNAs (ncRNAs) and cancer therapy-induced cardiotoxicity has received much attention and investigation. NcRNAs are non-protein-coding RNAs that impact gene expression post-transcriptionally. They include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). In several cancer treatments, such as chemotherapy, radiotherapy, and targeted therapy-induced cardiotoxicity, ncRNAs play a significant role in the onset and progression of cardiotoxicity. This review focuses on the mechanisms of ncRNAs in cancer therapy-induced cardiotoxicity, including apoptosis, mitochondrial damage, oxidative stress, DNA damage, inflammation, autophagy, aging, calcium homeostasis, vascular homeostasis, and fibrosis. In addition, this review explores potential ncRNAs-based biomarkers and therapeutic strategies, which may help to convert ncRNAs research into clinical practice in the future for early detection and improvement of cancer therapy-induced cardiotoxicity.

Relevance of Ferroptosis to Cardiotoxicity Caused by Anthracyclines: Mechanisms to Target Treatments.

Anthracyclines (ANTs) are a class of anticancer drugs widely used in oncology. However, the clinical application of ANTs is limited by their cardiotoxicity. The mechanisms underlying ANTs-induced cardiotoxicity (AIC) are complicated and involve oxidative stress, inflammation, topoisomerase 2ß inhibition, pyroptosis, immunometabolism, autophagy, apoptosis, ferroptosis, etc. Ferroptosis is a new form of regulated cell death (RCD) proposed in 2012, characterized by iron-dependent accumulation of reactive oxygen species (ROS) and lipid peroxidation. An increasing number of studies have found that ferroptosis plays a vital role in the development of AIC. Therefore, we aimed to elaborate on ferroptosis in AIC, especially by doxorubicin (DOX). We first summarize the mechanisms of ferroptosis in terms of oxidation and anti-oxidation systems. Then, we discuss the mechanisms related to ferroptosis caused by DOX, particularly from the perspective of iron metabolism of cardiomyocytes. We also present our research on the prevention and treatment of AIC based on ferroptosis. Finally, we enumerate our views on the development of drugs targeting ferroptosis in this emerging field.

Efficacy and safety of prophylactic intraoperative sac embolization in EVAR for abdominal aortic aneurysm: A meta-analysis.

Objective: We aimed to investigate the effectiveness and safety of prophylactic sac embolization during endovascular aneurysm repair (EVAR) in patients suffering from abdominal aortic aneurysms. Methods: We performed a systematic literature search of PubMed, Web of Science, EMbase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, Wanfang and China Biomedical Literature Database (CBM) to identify studies evaluating the outcomes of sac embolization vs. no embolization among patients who had received EVAR. The time limit of the search was from the establishing database to July 22, 2022. Outcome measures involved the type II endoleak rate, the other endoleak rate, the reintervention rate, mortality, and operation time. Fixed (no heterogeneity) or random effects models were constructed for each outcome. The outcomes are represented as the odds ratio (OR) with a 95% confidence interval (CI). Results: Among the 2,622 studies screened, 13 studies involving 747 participants were included in the review. The incidence of early-term type II endoleak (OR = 0.2, 95% CI (0.13,0.31), P < 0.00001), mid-term type II endoleak (OR = 0.23, 95% CI (0.15,0.37), P < 0.00001), late-term type II endoleak (OR = 0.27, 95% CI (0.16,0.46), P < 0.00001) and reintervention (OR = 0.50, 95% CI (0.37,0.78), P = 0.002) within the sac embolization group were significantly lower than those in the non-embolization group. No significant differences were observed between the two groups were found for the other endoleak rates (OR = 0.67, 95% CI (0.34,1.32), P = 0.25), mortality (OR = 0.64, 95% CI (0.25,1.66), P = 0.36) and operation time operation (MD = 5.76, 95% CI (-8.30,19.83), P = 0.42). Conclusions: EVAR combined with sac embolization effectively reduces the incidence of type II endoleak and the reintervention rate without enhancing the operation time. Therefore, more high-quality studies are still needed for validation due to the limited amount and quality of included literature. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022365648.

Enhanced Antiviral Ability by a Combination of Zidovudine and Short Hairpin RNA Targeting Avian Leukosis Virus.

Avian leukosis virus (ALV) causes tumor diseases in poultry and is circulating all over the world, leading to significant economic losses. In addition, mixed infection of ALV with other viruses is very common and is often reported to contaminate live vaccines. At present, there is no effective method to suppress the replication of ALV in vitro, so it is very difficult to remove it in mixed infection. As a retrovirus, the replication of ALV can be limited by reverse transcriptase (RT) inhibitors like zidovudine (AZT), but it also causes nontargeted cytotoxicity. To find the optimal solution in cytotoxicity and inhibition efficiency in vitro culture system, we firstly designed a combination therapy of AZT and short hairpin RNA (shRNA) targeting ALV and then verified its efficiency by multiple biological methods. Results showed that shRNA can effectively inhibit the expression of RT and then limit the replication of ALV. The combination of AZT and shRNA can significantly improve the antiviral efficiency in viral replication, shedding, and provirus assembly under the condition of low cytotoxicity. Overall, in this study, the combination therapy of AZT and shRNA targeting ALV showed excellent antiviral performance against ALV in vitro culture system. This method can be applied to multiple scenarios, such as the removal of ALV in mixed infection or the purification of contaminated vaccine strains.

Efficacy of endostatin combined with continuous transcatheter arterial infusion and chemoembolization on gastric cancer with liver metastasis and analysis of prognosis.

PURPOSE: To explore the efficacy and safety of Endostatin combined with continuous transcatheter arterial infusion (TAI) and transcatheter arterial chemoembolization (TACE) in the treatment of gastric cancer with liver metastasis, and analyze the prognosis. METHODS: 96 gastric cancer patients with liver metastasis treated in our hospital from September 2013 to September 2016 were collected and randomly divided into TAI+TACE group (n=48) and Endostatin+TAI+TACE group (n=48). The clinical efficacy, changes in the level of vascular endothelial growth factor (VEGF) before and after treatment, adverse reactions, postoperative tumor recurrence and patient survival were observed and recorded, and the possible influencing factors for prognosis were analyzed. RESULTS: In the Endostatin+TAI+TACE group and TAI+TACE group, the objective response rate (ORR) was 70.8% (34/48) and 47.9% (23/48), and the disease control rate (DCR) was 91.7% (44/48) and 83.3% (40/48), respectively. After treatment, the concentration of VEGF declined significantly in both groups compared with that before treatment, more obviously in the Endostatin+TAI+TACE group than in the TAI+TACE group. According to the follow-up results, both overall survival (OS) and progression-free survival (PFS) in the Endostatin+TAI+TACE group were evidently higher than those in the TAI+TACE group. The Cox regression analysis revealed that the grade of tumor differentiation and Endostatin combination therapy were independent factors influencing the prognosis of patients. CONCLUSION: Endostatin combined with TAI and TACE can obtain good short-term clinical efficacy in the treatment of gastric cancer with liver metastasis. Compared with those treated with chemotherapy alone, patients receiving Endostatin+TAI+TACE have significantly improved OS and PFS, a reduced level of VEGF and a lower incidence rate of adverse reactions, so Endostatin+TAI+TACE is worthy of clinical popularization and application.

Protective Effects of Ischemic Postconditioning on Livers in Rats with Limb Ischemia-Reperfusion via Glycogen Synthase Kinase 3 beta (GSK-3ß)/Fyn/Nuclear Receptor-Erythroid-2-Related Factor (Nrf2) Pathway.

BACKGROUND Ischemia/reperfusion (I/R) injury not only exists in ischemic tissues and organs, but also can cause damage to distant tissues and organs. As the largest metabolic organ of the human body, the liver is very vulnerable to injury after limb I/R. However, the mechanism of liver injury caused by limb I/R injury has not been fully elucidated. This study investigated the effect and mechanism of ischemic postconditioning (IPO) on the liver after hindlimb I/R in rats. MATERIAL AND METHODS A rat model of hindlimb I/R was established and treated by IPO. Liver function, changes of oxidative stress index and inflammation, Bcl-2 and Bax proteins, and apoptosis were assessed. The structural changes were observed by electron microscopy. GSK-3ß/Fyn/Nrf2 levels were detected by quantitative PCR and Western blot. RESULTS IPO significantly reduced serum AST, ALP, LDH, and ALT levels induced by I/R. Compared with the I/R group, the levels of SOD, GSH-Px, and CAT in the IPO group were significantly increased, while the levels of MDA, MPO, and ROS were significantly decreased. The IPO group had significantly higher Bcl-2 level and significantly lower Bax level compared to the I/R group. Consistently, IPO decreased the apoptosis rate induced by I/R. Furthermore, IPO lowered the levels of TNF-alpha, IL-1ß, IL-10, and INF-γ and alleviated the ultrastructural changes of hepatocytes. Finally, Nrf2, Fyn, and GSK-3ß mRNA and protein levels in the IPO group were significantly higher than in the I/R group. CONCLUSIONS IPO protects against liver injury caused by I/R injury of the hindlimb, possibly via the GSK-3ß/Fyn/Nrf2 pathway.

Prognosis of ß-adrenergic blockade therapy on septic shock and sepsis: A systematic review and meta-analysis of randomized controlled studies.

PURPOSE: ß-adrenoceptor antagonist (ß-blocker) may have potential in the treatment of septic shock and sepsis. However, the relevant research findings are still controversial. METHODS: We conducted a systematic review and meta-analysis to explore the efficacy of ß-blocker in patients with septic shock and sepsis. The primary sources of the reviewed studies through August 2018, with restriction on the language of English, were Pubmed and Embase. Randomized controlled trials (RCT) were included to evaluate the efficacy of ß-blocker in the treatment of septic shock and sepsis. Meta analysis was performed using a random effect model. Two researchers independently searched articles, extracted data, and assessed the quality of the included studies. RESULTS: A total of 6 studies related to 5 original RCTs were qualified for inclusion in this systematic review and meta-analysis with a total of 363 patients with sepsis and/or septic shock. ß-blocker was associated with a significantly decreased 28-day mortality compared to usual treatment group as the control (RR = 0.59, 95%CI: 0.48, 0.74; P < 0.00001). Heart rate in ß-blocker was significantly lower than that in the standard care group (SMD = -2.01, 95%CI: -3.03, -0.98; P = 0001). CONCLUSION: ß-blocker of esmolol is safe and effective in improving 28-day mortality and controlling ventricular rate in patients with sepsis after fluid resuscitation, and has no significant adverse effect on tissue perfusion.

The fucoidan from the brown seaweed Ascophyllum nodosum ameliorates atherosclerosis in apolipoprotein E-deficient mice.

Hyperlipidemia is a major cause of atherosclerosis. Reverse cholesterol transport (RCT) is believed to attenuate hyperlipidemia and the progression of atherosclerosis. Although fucoidans are reported to have hypolipidemic effects, the underlying mechanisms are unclear. Furthermore, few reports have revealed the anti-atherosclerotic effects and the underlying mechanisms of fucoidans. This study was designed to investigate the anti-atherosclerotic effect and mechanisms of the fucoidan from seaweed A. nodosum. Our results demonstrated that the fucoidan administration ameliorated atherosclerotic lesion and lipid profiles in a dose-dependent manner in the apolipoprotein E-deficient (apoE-/-) mice fed a high-fat diet. In the apoE-/- mice liver, the fucoidan treatment significantly increased the expression of scavenger receptor B type 1 (SR-B1), peroxisome proliferator-activated receptor (PPAR) α and ß, liver X receptor (LXR) α, ATP-binding cassette transporter (ABC) A1 and ABCG8; and markedly decreased the expression of PPARγ and sterol regulatory element-binding protein (SREBP) 1c, but not low-density lipoprotein receptor, proprotein convertase subtilisin/kexin type 9, cholesterol 7 alpha-hydroxylase A1, LXRß and ABCG1. In the small intestine of the apoE-/- mice, the fucoidan treatment significantly reduced the expression of Niemann-Pick C1-like 1 (NPC1L1) and dramatically improved ABCG8 levels. These results demonstrated for the first time that the fucoidan from A. nodosum attenuated atherosclerosis by regulating RCT-related genes and proteins expression in apoE-/- mice. In summary, this fucoidan from A. nodosum may be explored as a potential compound for prevention or treatment of hyperlipidemia-induced atherosclerosis.

Effects of puerarin on blood lipids and inflammatory factors in rats with lower limb arteriosclerosis obliterans

This study investigated the effects of puerarin (PUE) on blood lipid and inflammatory factor levels in rats with lower limb arteriosclerosis obliterans (ASO). Sixty rats were randomly divided into control, model, simvastatin, low-PUE, middle-PUE and high-dose PUE group. The animals in later 5 groups were with lower limb ASO, and the later 4 groups were given 1 mg/kg simvastatin and 5, 10 and 20 mg/kg PUE, respectively. The blood lipid and inflammatory factor levels were determined. Results showed that, the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) level in model group were significantly increased (P <0.01), while the high-density lipoprotein cholesterol (HDL-C) was significantly decreased (P <0.01). Compared with model group, TC, TG, LDL-C, IL-6, TNF-α and hs-CRP in high-dose PUE and simvastatin group were significantly decreased (P <0.01 or P <0.05), and HDL level was significantly increased (P <0.01 or P <0.05). There was no significant difference of each index between simvastatin and high-dose PUE group (P >0.05). PUE can obviously decrease the blood lipid and inflammatory factor levels in rats with lower limb ASO.

The role of lncRNA MALAT1 in bone metastasis in patients with non-small cell lung cancer.

lncRNA metastasis-associated lung adencarcinoma transcript 1 (MALAT1) plays an important role in the metastasis of lung cancer. Yet, its role in bone metastasis and the related mechanism remain unknown. The present study aimed to investigate the role of lncRNA MALAT1 in the bone metastasis of non-small cell lung cancer (NSCLC), including the expression pattern in tumor tissues, and the effect on the apoptosis, proliferation, migration and invasion of NSCLC cells. The expression level of MALAT1 in NSCLC tissues with/without bone metastasis and in NSCLC cell lines with (ACC-LC-319/bone2)/without (SPC­A1) bone metastatic ability was determined with qRT-PCR and compared with t-test. si-MALAT1 was used to downregulate the expression of MALAT1 in ACC-LC-319/bone2 cells. The proliferation ability was assessed by MTT assay, and the apoptosis, migration, invasion and tumorigenesis in vivo were also assessed to detect the effect of MALAT1 expression on NSCLC cells. In conclusion, the present study found that MALAT1 was significantly highly expressed in NSCLC tissues with bone metastasis and in NSCLC cell lines with high bone metastatic ability (P<0.0001). Downregulation of MALAT1 expression significantly inhibited proliferation and induced cell apoptosis in comparing with the negative controls. Our results also revealed that MALAT1 significantly increased the migration, invasion and tumorigenesis in vivo, which suggests its important role in the bone metastasis of NSCLC.

Bloodletting at Jing-well points decreases interstitial fluid flow in the thalamus of rats.

OBJECTIVE: To investigate the changes in the neuronal microenvironment of the middle cerebral artery (MCA) territory induced by Jing-well points bloodletting acupuncture (WPBA) and to explore the neuroprotective mechanism of WPBA in stroke. METHODS: Adult male Sprague Dawley (n = 32) rats were randomly divided into four groups of eight animals each: WPBA-thalamus group (WT), WPBA-caudate nucleus group (WC), sham-control thalamus group (ST) and sham-control caudate nucleus group (SC). Animals in the WT and WC groups received 2 µL of the extracellular tracer gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) injected into the thalamus or caudate nucleus, respectively, and 12 Jing-well points in the distal ends of the rats' digits were used for WPBA. Although 2 µL of Gd-DTPA was injected into the thalamus or caudate nucleus, respectively, for animals in the two sham groups (ST and SC), no acupuncture or bloodletting was performed. Brain extracellular space and interstitial fluid flow parameters were measured using Gd-DTPA-enhanced magnetic resonance imaging. RESULTS: The brain interstitial fluid flow speed was decreased in the thalamus after WPBA, with a significantly lower Gd-DTPA clearance rate and longer half-life of Gd-DTPA in the thalamus of treated rats than those in sham-control rats [WPBA-treated rats' clearance rate, (7.47 ± 3.15) x 10(-5)/s (P.= 0.009); half-life, (1.52 ± 0.13) h, P = 0.000]. By contrast, no significant changes in brain extracellular space and interstitial fluid flow parameters were detected in the caudate nucleus after WPBA (P = 0.649). In addition, no differences in the morphology of the brain extracellular space or the final distribution of the traced brain interstitial fluid were demonstrated between the WT and WC groups (P = 0.631, P = 0.970, respectively). CONCLUSION: The WPBA decreased the speed of the local thalamic ISF flow in rats, which is assumed to be a beneficial protection by down-modulated the metabolic rate of the attacked neurons under stroke.

Expression of XB130 in human ductal breast cancer.

OBJECTIVES: XB130 is involved in gene regulation, cell proliferation, cell survival, cell migration, and tumorigenesis. In the present study, we first evaluated the expression of the XB130 and its prognostic significance in breast cancer. Then we evaluated whether XB130 could be a target for therapy in breast cancer. MATERIALS AND METHODS: Immunohistochemistry was used to assess the level of XB130 protein in surgically resected, formalin-fixed, paraffin-embedded breast cancer specimens. Associations between XB130 and the postoperative prognosis of patients with breast cancer were evaluated. We evaluated the effect of XB130 inhibited by RNA interference on proliferation, invasion and apoptosis in vitro in a metastatic subclone of MCF-7 breast cancer cell line (LM-MCF-7). The effect of XB130 silencing alone or in combination with gemcitabine on LM-MCF-7 cells apoptosis was also investigated. RESULTS: XB130 protein was present in the cytoplasm of malignant cells, and not in the normal breast tissues. There was correlation between the presence of XB130 in tumour cells and lymph node status, tumor classification and clinical stage. XB130 expression level was significantly associated with recurrence-free and overall survival. Furthermore, multivariate Cox regression analyses revealed that positive XB130 was an independent risk factor for overall survival and recurrence free survival. XB130 silencing alone inhibits tumor growth and induces apoptosis in the LM-MCF-7 cells. Depletion of the XB130 in combination with gemcitabine resulted in marked apoptotic and necrotic cell death in LM-MCF-7 cells. CONCLUSIONS: XB130 could be useful as a prognostic marker of recurrence-free and overall survival in invasive breast cancer, as well as for the response to chemotherapy.