Inhibition of MALT1 reduces ferroptosis in rat hearts following ischemia/reperfusion via enhancing the Nrf2/SLC7A11 pathway.

The dysregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and/or solute carrier family 7 member 11 (SLC7A11) is believed to contribute to ferroptosis in the hearts suffered ischemia/reperfusion (I/R), but the mechanisms behind the dysregulation of them are not fully elucidated. Mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1) can function as a paracaspase to cleave specified substrates and it is predicted to interact with Nrf2. This study aims to explore whether targeting MALT1 can reduce I/R-induced ferroptosis via enhancing the Nrf2/SLC7A11 pathway. The SD rat hearts were subjected to 1h-ischemia plus 3h-reperfusion to establish the I/R injury model, which showed myocardial injuries (increase in infarct size and creatine kinase release) and up-regulation of MALT1 while downregulation of Nrf2 and SLC7A11 concomitant with the increased ferroptosis, reflecting by an increase in glutathione peroxidase 4 (GPX4) level while decreases in the levels of acyl-CoA synthetase long chain family member 4 (ACSL4), total iron, Fe2+ and lipid peroxidation (LPO); these phenomena were reversed in the presence of MI-2, a specific inhibitor of MALT1. Consistently, similar results were achieved in the cultured cardiomyocytes subjected to 8h-hypoxia plus 12h-reoxygenation. Furthermore, micafungin, an antifungal drug, could also exert beneficial effect on mitigating myocardial I/R injury via inhibition of MALT1. Based on these observations, we conclud that inhibition of MALT1 can reduce I/R-induced myocardial ferroptosis through enhancing the Nrf2/SLC7A11 pathway; and MALT1 may be used as a potential target to seek novel or existing drugs (such as micafungin) for treating myocardial infarction.

An integrative investigation of developmental toxicities induced by triphenyltin in a larval coral reef fish, Amphiprion ocellaris.

Triphenyltin (TPT) is widely distributed on coastlines, which makes coral reef fish a potential target of TPT pollution. However, the negative effects of TPT on coral reef fish remain poorly understood. Therefore, in the present study, the larval coral reef fish Amphiprion ocellaris was used to investigate the developmental toxicities of TPT at environmentally relevant concentrations (0, 1, 10 and 100 ng/L). After TPT exposure for 14 d, the cumulative mortality increased, and growth was suppressed. In addition, TPT exposure inhibited the development of melanophores and xanthophores and delayed white strip formation, which might be responsible for the disruption of the genes (erbb3b, mitfa, kit, xdh, tyr, oca2, itk and trim33) related to pigmentation. TPT exposure also attenuated ossification of head skeletal elements and the vertebral column and inhibited the expression of genes (bmp2, bmp4 and sp7) related to skeletal development. The observed developmental toxicities on growth, pigmentation and skeleton development might be associated with the disruption of thyroid hormones and the genes related to thyroid hormone regulation (tshß, thrα, thrß, tg, tpo, dio2, and ttr). In addition, TPT exposure interfered with locomotor and shoaling behavior, and the related genes dbh, avp and avpr1aa. Taken together, our results suggest that TPT pollution might threaten the development of one of the most iconic coral reef fish, which might produce disastrous consequences on the health of coral reef ecosystems.

Effectiveness of moist dressings in wound healing after surgical suturing: A Bayesian network meta-analysis of randomised controlled trials.

The moist healing theory proves that a moderately moist and airtight environment is conducive to wound healing. However, different moist dressings have different functions. We aim to evaluate the effects of moist dressings on wound healing after surgical suturing and identify superior moist dressings. Randomised controlled trials investigating the application of moist dressings were retrieved from electronic databases, including PubMed, EMBASE, Web of Science, and the Cochrane Library. Wound healing, surgical site infection (SSI), and times of dressing change were assessed. The values of the surface under the cumulative ranking (SUCRA) curve were calculated based on the Bayesian network meta-analysis. Inconsistency tests and funnel plots were applied to analyse the consistency and publication bias. All the analysis complies with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 Checklist and AMSTAR (Assessing the Methodological Quality of Systematic Reviews) Guidelines. Sixteen randomised controlled trials involving 4444 patients were pooled in the network meta-analysis. The ionic silver dressing (SUCRA, 93%) ranked first in wound healing, the metallic silver dressing (SUCRA, 75.9%) ranked first in SSI, and the hydrocolloid dressing (SUCRA, 73.9%) ranked first in times of dressing change. Inconsistency was only observed in wound healing, and no publication bias was observed in this study. The effects of moist dressings are better than gauze dressings in the process of wound healing. The ionic silver dressing is effective in wound healing, whereas the metallic silver dressing is effective in SSI prevention. The hydrocolloid dressing requires the fewest times of dressing change. More high-quality RCTs are required to support the network meta-analysis.

TLR7 agonist RO7020531 versus placebo in healthy volunteers and patients with chronic hepatitis B virus infection: a randomised, observer-blind, placebo-controlled, phase 1 trial.

BACKGROUND: Toll-like receptor 7 (TLR7) agonists augment immune activity and have potential for the treatment of chronic hepatitis B virus (HBV) infection. We aimed to assess the safety and tolerability of RO7020531 (also called RG7854), a prodrug of the TLR7 agonist RO7011785, in healthy volunteers and patients with chronic HBV infection. METHODS: This randomised, observer-blind, placebo-controlled, phase 1 study was done in two parts. Part 1 was done at one site in New Zealand and part 2 was done at 12 sites in Bulgaria, Hong Kong, Italy, New Zealand, the Netherlands, Taiwan, Thailand, and the UK. In part 1, healthy volunteers were randomly assigned (4:1) within one of eight dose cohorts (3 mg, 10 mg, 20 mg, 40 mg, 60 mg, 100 mg, 140 mg, or 170 mg) to receive a single RO7020531 dose or placebo or randomly assigned (4:1) within one of three dose cohorts (100 mg, 140 mg, or 170 mg) to receive either RO7020531 or placebo every other day for 13 days. In part 2, nucleoside or nucleotide analogue-suppressed patients with chronic HBV infection were randomly assigned (4:1) within cohorts 1-3 (150 mg, 150 mg, or 170 mg) to receive either RO7020531 or placebo and treatment-naive patients with chronic HBV infection were randomly assigned (3:1) in cohort 4 to receive either 150 mg of RO7020531 or placebo. Patients were treated every other day for 6 weeks. Study medication was administered orally to participants after they had fasted. Study participants and investigational staff were masked to treatment allocation. The primary outcome was the safety and tolerability of RO7020531, as measured by the incidence and severity of adverse events and the incidence of laboratory, vital sign, and electrocardiogram abnormalities, and was analysed in all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT02956850, and the study is complete. FINDINGS: Between Dec 12, 2016, and March 21, 2021, 340 healthy volunteers were screened in part 1, of whom 80 were randomly assigned in the single ascending dose study (eight assigned RO7020531 in each cohort and 16 assigned placebo) and 30 were randomly assigned in the multiple ascending dose study (eight assigned RO7020531 in each cohort and six assigned placebo), and 110 patients were screened in part 2, of whom 30 were randomly assigned in cohorts 1-3 (16 assigned RO7020531 150 mg, eight assigned RO7020531 170 mg, and six assigned placebo) and 20 were randomly assigned in cohort 4 (15 assigned RO7020531 and five assigned placebo). All randomly assigned participants received at least one dose of a study drug and were included in the safety analysis. All tested doses of RO7020531 were safe and had acceptable tolerability in healthy volunteers and patients. The most frequent treatment-related adverse events among the total study population were headache (15 [9%] of 160 participants), influenza-like illness (seven [4%] of 160 participants), and pyrexia (ten [6%] of 160 participants). Most adverse events were mild and transient. There were no severe or serious adverse events in healthy volunteers. In the patient cohorts, there was one severe adverse event (influenza-like illness with 170 mg of RO7020531) and one serious adverse event (moderate influenza-like illness with a 3-day hospitalisation in a treatment-naive patient receiving RO7020531). There were no treatment-related deaths. INTERPRETATION: Due to acceptable safety and tolerability, RO7020531 should continue to be developed for the treatment of patients with chronic HBV infection. FUNDING: F Hoffmann-La Roche.

Comparative safety of multiple doses of erythropoietin for the treatment of traumatic brain injury: A systematic review and network meta-analysis.

Introduction: Over the past few decades, advances in traumatic brain injury (TBI) pathology research have dynamically enriched our knowledge. Therefore, we aimed to systematically elucidate the safety and efficacy of erythropoietin (EPO) dosing regimens in patients with TBI. Methods: Data search included PubMed, the Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov for related research published before July 2022. The network meta-analysis was conducted using ADDIS 1.16.8, and the CINeMA tool was used to assess the quality level of evidence. Results: A total of six RCTs involving 981 patients were included in the network meta-analysis. EPO did not significantly reduce mortality in patients with TBI, but its risk of death decreased with increasing dosage (odds ratio (OR) of 12,000u vs. placebo = 0.98, 95% CI: 0.03-40.34; OR of group 30,000u vs. placebo = 0.56, 95% CI: 0.06-5.88; OR of 40,000u vs. placebo = 0.35, 95% CI: 0.01-9.43; OR of 70,000u vs. placebo = 0.29, 95% CI: 0.01-9.26; OR of group 80,000u vs. placebo = 0.22, 95% CI: 0.00-7.45). A total of three studies involving 739 patients showed that EPO did not increase the incidence of deep vein thrombosis in patients with TBI. However, the risk tended to rise as the dosage increased. Another two studies demonstrated that EPO did not increase the incidence of pulmonary embolism. The quality of evidence for all outcomes was low to moderate. Conclusion: Although the efficacy of EPO was not statistically demonstrated, we found a trend toward an association between EPO dosage and reduced mortality and increased embolic events in patients with TBI. More high-quality original studies should be conducted to obtain strong evidence on the optimal dosage of EPO. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=272500. The study protocol was registered with PROSPERO (CRD42021272500).

Application of probiotics, prebiotics and synbiotics in patients with breast cancer: a systematic review and meta-analysis protocol for randomised controlled trials.

INTRODUCTION: Breast cancer has become a common tumour that threatens women's physical and mental health. Microbial agents play an important role in maintaining the balance of gut microbiota and modulating intestinal immunity, anti-inflammatory and antioxidant effects. Available evidence points to a strong association between them and breast cancer. However, there has been no systematic review of the effects of microbial agents in patients with breast cancer. This protocol aims to explore the effectiveness and safety of probiotics, prebiotics and synbiotics in patients with breast cancer. METHODS AND ANALYSIS: We will search the following electronic databases for relevant randomised controlled trials: PubMed, EMBASE, Cochrane Library and Web of Science. Grey literature and reference lists of original studies will also be searched to avoid omissions. We will use the Cochrane Collaboration's Risk of Bias tool to assess the quality of the included studies. The primary outcomes include patients' arm oedema volume, changes in gut microbiota composition and anthropometric parameters. Two independent reviewers will perform literature screening, data extraction and risk of bias assessment. Data synthesis will be performed using descriptive analysis or meta-analysis. The quality of the evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. ETHICS AND DISSEMINATION: The data for systematic reviews are derived from published original studies and do not require review and approval by the ethics committee. The results will be disseminated through a peer-reviewed journal and conferences. PROSPERO REGISTRATION NUMBER: CRD42022311502.

Comprehensive analysis of treatment-related adverse events of immunotherapy in advanced gastric or gastroesophageal junction cancer: A meta-analysis of randomized controlled trials.

AIMS: Immune checkpoint inhibitors (ICIs) have been recognized as an effective treatment for advanced gastric or gastroesophageal junction cancer (AG/GEJC). However, the safety of ICIs in patients has not been established. We aimed to systematically assess the risk of all common treatment-related adverse events (TRAEs) in immunotherapy of AG/GEJC. METHODS: A systematic search of randomized controlled trials (RCTs) published until May 2022 was performed using PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. And a meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: A total of nine RCTs, including 2918 patients, met the eligibility criteria. The pooled overall incidences of all grade TRAEs, grade 3 or higher TRAEs and treatment-related death were 54.5% (95% confidence interval [CI]: 48.7%-60.2%, I2=75.55%), 12.8% (95% CI: 10.2%-15.7%, I2=51.61%) and 0.11% (95% CI: 0.00%-0.51%, I2=1.63%). Subgroup analyses showed that CTLA-4 inhibitors had a higher risk of any type of TRAEs, when compared with PD-1 and PD-L1 inhibitors. Meta-regression showed significant correlation between all grade TRAEs and proportion of female. Fatigue and diarrhoea were involved in common TRAEs. CONCLUSIONS: Our study provides a comprehensive overview of ICIs-associated AEs in AG/GEJC. Immunotherapy did not have a significantly increased risk experiencing any type of TRAEs, and ICIs had a more manageable safety profile than chemotherapy. These findings provide important guidance to clinicians in counseling and management of patients with AG/GEJC.

The SPATA2/CYLD pathway contributes to doxorubicin-induced cardiomyocyte ferroptosis via enhancing ferritinophagy.

Ferroptosis is an iron-dependent cell death and contributes to doxorubicin-induced cardiotoxicity, but the mechanisms behind intracellular iron overload in cardiomyocyte after administration of doxorubicin remain largely unknown. Ferritinophagy is a selective type of autophagy and could be a novel source for intracellular free iron. Spermatogenesis-associated protein 2 (SPATA2), a member of the TNF signaling pathway, can recruit cylindromatosis (CYLD, a deubiquitinating enzyme) to regulate cell death. This study aims to explore whether ferritinophagy is the source for intracellular iron overload in cardiomyocyte upon doxorubicin treatment and whether the SPATA2/CYLD pathway is involved in regulation of nuclear receptor coactivator 4 (NCOA4) level, the selective cargo receptor for ferritinophagy. The C57BL/6J mice were subjected to a single injection of doxorubicin, which showed the compromised cardiac functions, accompanied by the upregulation of SPATA2 and CYLD and the enhanced interaction between them, the increases in ferritinophagy (reflecting by increases in NCOA4 and ratio of LC3Ⅱ/LC3Ⅰ while decreases in NCOA4 ubiquitination and ferritin) and ferroptosis (reflecting by intracellular iron overload and increase of acyl-CoA synthetase long chain family member 4). Consistently, similar results were achieved in the cultured cardiomyocytes after incubation with doxorubicin. Knocked down of SPATA2 notably reduced doxorubicin-induced cardiomyocyte injury concomitant with the attenuated ferritinophagy and the decreased ferroptosis. Based on these observations, we conclude that a novel pathway of SPATA2/CYLD has been identified, which contributes to doxorubicin-induced cardiomyocyte ferroptosis via enhancing ferritinophagy through a mechanism involving the deubiquitination of NCOA4.

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.

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.

Gibberellic acid application on biomass, oxidative stress response, and photosynthesis in spinach (Spinacia oleracea L.) seedlings under copper stress.

The mechanism of Cu tolerance in plants and its control measures are of considerable significance for the remediation of Cu-contaminated soils. Gibberellic acid (GA3) is involved in plant growth and development and in the response to heavy metal stress. In the present study, changes in the biomass, oxidative stress response responses, and photosynthesis of spinach seedlings were examined under Cu stress with exogenous GA3 applied at concentrations of 0, 3, 5, 10, 20, 40, 60, or 80 mg L-1. Under Cu stress, the plant Cu concentration and oxidative damage were greater, photosynthetic parameters and biomass declined, and antioxidant enzyme activities and the proline concentration increased. However, spinach growth did not terminate, indicating that spinach seedlings had strong Cu tolerance. When low concentrations of GA3 (3-5 mg L-1) were added to Cu-stressed spinach seedlings, the damage caused by Cu stress to spinach seedlings was reduced, and the Cu tolerance of spinach seedlings was enhanced, which mainly manifested as reduced oxidation damage, an increased proline concentration, elevated antioxidant enzyme activities, decreased Cu concentration in leaves, and increased Cu concentration in roots, increased photosynthetic parameters, and an increased in the total biomass. In contrast, additions of GA3 at concentrations higher than 40 mg L-1 intensified oxidative damage and decreased the activities of antioxidant enzymes, photosynthetic parameters, and biomass. Additionally, the Cu concentration increased in leaves and decreased Cu concentration in roots, indicating that high concentrations of GA3 aggravated stress damage and severely influenced physiological functions in spinach seedlings. In summary, the application of 3-5 mg L-1 GA3 to spinach seedlings in Cu-contaminated soil can be used to reduce Cu toxicity to plants and increase Cu tolerance.

The association between dietary fatty acid intake and the risk of developing preeclampsia: a matched case-control study.

The association between dietary fat intake during pregnancy and the risk of developing preeclampsia has been examined in many epidemiological studies, but the results remain inconsistent. The aim of this study was to clarify this association in pregnant Chinese women. After conducting 1:1 matching, 440 pairs consisting of pregnant women with preeclampsia and hospital-based, healthy pregnant women matched by gestational week (± 1 week) and age (± 3 years) were recruited. A 79-item semi-quantitative food frequency questionnaire administered during face-to-face interviews was used to estimate the participants' dietary intake of fatty acids. We found that the intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were inversely associated with the risk of developing preeclampsia. Compared with the lowest quartile intake, the multivariate-adjusted odds ratios (95% confidence interval) of the highest quartile intake were 0.42 (0.26-0.68, p-trend < 0.001) for EPA, 0.52 (0.3-0.83, p-trend = 0.005) for DHA, and 0.41 (0.19-0.88, p-trend = 0.007) for AA. However, we did not observe any significant associations between the intake of total fatty acids, saturated fatty acids, and mono-unsaturated fatty acids and the risk of developing preeclampsia. Our results showed that the dietary intake of long-chain polyunsaturated fatty acids (i.e., EPA, DHA, and AA) may protect pregnant Chinese women against the development of preeclampsia.

Efficacy and safety of islet autotransplantation after total pancreatectomy in chronic pancreatitis: A systematic review and meta-analysis including 17 studies.

AIMS: Islet autotransplantation (IAT), in conjunction with total pancreatectomy (TP), is used to relieve pain in patients with chronic pancreatitis (CP), while reducing the incidence of brittle diabetes. We aimed to evaluate the efficacy and safety of IAT after TP (TPIAT) in this setting. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials since 1977. Data were extracted from published papers. Random-effects meta-analysis and meta-regression models were built to assess the outcomes and effect of different factors. Subgroup and sensitivity analyses were conducted to examine the between-study heterogeneity, which was assessed using Cochrane's Q and I2 statistic. RESULTS: A total of 17 studies, including 1024 patients, met the eligibility criteria. The median cohort size was 21 patients (range: 5-409). The pooled incidence rates of insulin independence, narcotic independence and mortality at last follow-up were 11.47 per 100 patient-years (95% CI: 6.79-21.60, I2=91.0%), 18.11 per 100 patient-years (95% CI: 5.29-62.04, I2=98.8%) and 2.88 per 100 patient-years (95% CI: 1.75-4.74, I2=46.8%), respectively. However, the heterogeneity level of our results was high, which was due to differences in research methods and definitions of outcomes between studies. Therefore, our results should be interpreted with caution. CONCLUSIONS: TPIAT can effectively relieve pain and reduce the risk of surgical diabetes with no increase in mortality or morbidity. Prospective, randomized, clinical trials are required to further evaluate selection of patients and the timing of TPIAT.

Bioinformatic prediction of critical genes and pathways involved in longevity in Drosophila melanogaster.

The pursuit of longevity has been the goal of humanity since ancient times. Genetic alterations have been demonstrated to affect lifespan. As increasing numbers of pro-longevity genes and anti-longevity genes have been discovered in Drosophila, screening for functionally important genes among the large number of genes has become difficult. The aim of the present study was to explore critical genes and pathways affecting longevity in Drosophila melanogaster. In this study, 168 genes associated with longevity in D. melanogaster were collected from the Human Ageing Genomic Resources (HAGR) database. Network clustering analysis, network topological analysis, and pathway analysis were integrated to identify key genes and pathways. Quantitative real-time PCR (qRT-PCR) was applied to verify the expression of genes in representative pathways and of predicted genes derived from the gene-gene sub-network. Our results revealed that six key pathways might be associated with longevity, including the longevity-regulating pathway, the peroxisome pathway, the mTOR-signalling pathway, the FOXO-signalling pathway, the AGE-RAGE-signalling pathway in diabetic complications, and the TGF-beta-signalling pathway. Moreover, the results revealed that six key genes in representative pathways, including Cat, Ry, S6k, Sod, Tor, and Tsc1, and the predicted genes Jra, Kay, and Rheb exhibited significant expression changes in ageing D. melanogaster strain w1118 compared to young ones. Overall, our results revealed that six pathways and six key genes might play pivotal roles in regulating longevity, and three interacting genes might be implicated in longevity. The results will not only provide new insight into the mechanisms of longevity, but also provide novel ideas for network-based approaches for longevity-related research.

Enhanced CO2 biofixation and protein production by microalgae biofilm attached on modified surface of nickel foam.

In this work, a photobioreactor with microalgae biofilm was proposed to enhance CO2 biofixation and protein production using nickel foam with the modified surface as the carrier for immobilizing microalgae cells. The results demonstrated that, compared with microalgae suspension, microalgae biofilm lowered mass transfer resistance and promoted mass transfer efficiency of CO2 from the bubbles into the immobilized microalgae cells, enhancing CO2 biofixation and protein production. Moreover, parametric studies on the performance of the photobioreactor with microalgae biofilm were also conducted. The results showed that the photobioreactor with microalgae biofilm yielded a good performance with the CO2 biofixation rate of 4465.6 µmol m-3 s-1, the protein concentration of effluent liquid of 0.892 g L-1, and the protein synthesis rate of 43.11 g m-3 h-1. This work will be conducive to the optimization design of microalgae culture system for improving the performance of the photobioreactor.

Baicalein Exerts Beneficial Effects in d-Galactose-Induced Aging Rats Through Attenuation of Inflammation and Metabolic Dysfunction.

Baicalein is a flavonoid isolated from the roots of Scutellaria baicalensis Georgi. This study aimed to ascertain the effects and potential underlying mechanisms of baicalein in d-galactose (d-gal)-induced aging rat model by integration of behavior examination, biochemical detection, and 1H nuclear magnetic resonance (NMR)-based metabolomic approach. Our findings suggest that baicalein significantly attenuated memory decline in d-gal-induced aging model, as manifested by increasing recognition index in novel object recognition test, shortening latency time, and increasing platform crossings in Morris water maze test. Baicalein significantly inhibited the releases of inflammatory mediators such as nitric oxide, interleukin-6, interleukin-1 beta, and tumor necrosis factor-α in d-gal-induced aging model. Metabolomic study revealed that 10 endogenous metabolites in cerebral cortex were considered as potential biomarkers of baicalein for its protective effect. Further metabolic pathway analysis showed that the metabolic alterations were associated with alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism, inositol phosphate metabolism, and energy metabolism. These data indicate that baicalein improves learning and memory dysfunction in d-gal-induced aging rats. This might be achieved through attenuation of inflammation and metabolic dysfunction.

MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis.

DNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite for B-cell progenitor survival. However, the transcription factors that promote DSB repair in B cells are not known. Here we show that MEF2C enhances the expression of DNA repair and recombination factors in B-cell progenitors, promoting DSB repair, V(D)J recombination and cell survival. Although Mef2c-deficient mice maintain relatively intact peripheral B-lymphoid cellularity during homeostasis, they exhibit poor B-lymphoid recovery after sub-lethal irradiation and 5-fluorouracil injection. MEF2C binds active regulatory regions with high-chromatin accessibility in DNA repair and V(D)J genes in both mouse B-cell progenitors and human B lymphoblasts. Loss of Mef2c in pre-B cells reduces chromatin accessibility in multiple regulatory regions of the MEF2C-activated genes. MEF2C therefore protects B lymphopoiesis during stress by ensuring proper expression of genes that encode DNA repair and B-cell factors.

Protective effect of lycopene on high-fat diet-induced cognitive impairment in rats.

A Western diet, high in saturated fats, has been linked to the development of cognitive impairment. Lycopene has recently received considerable attention for its potent protective properties demonstrated in several models of nervous system dysfunction. However, it remains unclear whether lycopene exerts protective effects on cognition. The present study aimed to investigate the protective effects of lycopene on learning and memory impairment and the potential underlying mechanism in rats fed a high-fat diet (HFD). One-month-old male rats were fed different diets for 16 weeks (n=12 per group), including a standard chow diet (CD), a HFD, or a HFD plus lycopene (4mg/kg, oral gavage in the last three weeks). Behavioral testing, including the Morris water maze (MWM), object recognition task (ORT), and anxiety-like behavior in an open field (OF), were assessed at week 16. The dendritic spine density and neuronal density in the hippocampal CA1 subfield were subsequently measured. The results indicate that HFD consumption for 16 weeks significantly impaired spatial memory (P<0.001), working memory (P<0.01), and object recognition memory (P<0.01), decreased the dendritic spine density (P<0.001), damaged pyramidal neurons in the CA1 subfield (P<0.001) compared with the CD group. However, lycopene significantly attenuated learning and memory impairments and prevented the reduction in dendritic spine density (P<0.001). Thus, this study indicated that lycopene helps to protect HFD induced cognitive dysfunction.

Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology.

Traditional Chinese medicine (TCM) has been used to treat tumors for years and has been demonstrated to be effective. However, the underlying molecular mechanisms of herbs remain unclear. This study aims to ascertain molecular targets of herbs prolonging survival time of patients with advanced hepatocellular carcinoma (HCC) based on network pharmacology, and to establish a research method for accurate treatment of TCM. The survival benefit of TCM treatment with Chinese herbal medicine (CHM) was proved by Kaplan-Meier method and Cox regression analysis among 288 patients. The correlation between herbs and survival time was performed by bivariate correlation analysis. Network pharmacology method was utilized to construct the active ingredient-target networks of herbs that were responsible for the beneficial effects against HCC. Cox regression analysis showed CHM was an independent favorable prognostic factor. The median survival time was 13 months and the 5-year overall survival rates were 2.61% in the TCM group, while there were 6 months, 0 in the non-TCM group. Correlation analysis demonstrated that 8 herbs closely associated with prognosis. Network pharmacology analysis revealed that the 8 herbs regulated multiple HCC relative genes, among which the genes affected proliferation (KRAS, AKT2, MAPK), metastasis (SRC, MMP), angiogenesis (PTGS2) and apoptosis (CASP3) etc.

Glutathione S-transferase M1 polymorphism and esophageal cancer risk: An updated meta-analysis based on 37 studies.

AIM: To evaluate the relationship between glutathione S-transferase M1 (GSTM1) polymorphism and susceptibility to esophageal cancer (EC). METHODS: A comprehensive search of the United States National Library of Medicine PubMed database and the Elsevier, Springer, and China National Knowledge Infrastructure databases for all relevant studies was conducted using combinations of the following terms: "glutathione S-transferase M1", "GSTM1", "polymorphism", and "EC" (until November 1, 2014). The statistical analysis was performed using the SAS software (v.9.1.3; SAS Institute, Cary, NC, United States) and the Review Manager software (v.5.0; Oxford, England); crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between the GSTM1 null genotype and the risk of EC. RESULTS: A total of 37 studies involving 2236 EC cases and 3243 controls were included in this meta-analysis. We observed that the GSTM1 null genotype was a significant risk factor for EC in most populations (OR = 1.33, 95%CI: 1.12-1.57, P heterogeneity < 0.000001, and I (2) = 77.0%), particularly in the Asian population (OR = 1.53, 95%CI: 1.26-1.86, P heterogeneity < 0.000001, and I (2) = 77.0%), but not in the Caucasian population (OR = 1.02, 95%CI: 0.87-1.19, P heterogeneity = 0.97, and I (2) = 0%). CONCLUSION: The GSTM1 null polymorphism may be associated with an increased risk for EC in Asian but not Caucasian populations.