Synthesis, Structural Characterization, and Biological Activities of 1,3,4- Thiadiazole Derivatives Containing Sulfonylpiperazine Structures.

To develop novel bacterial biofilm inhibiting agents, a series of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures were designed, synthesized, and characterized using 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry. Meanwhile, their biological activities were evaluated, and the ensuing structure-activity relationships were discussed. The bioassay results showed the substantial antimicrobial efficacy exhibited by most of the compounds. Among them, compound A24 demonstrated a strong efficacy with an EC50 value of 7.8 µg/mL in vitro against the Xanthomonas oryzae pv. oryzicola (Xoc) pathogen, surpassing commercial agents thiodiazole copper (31.8 µg/mL) and bismerthiazol (43.3 µg/mL). Mechanistic investigations into its anti-Xoc properties revealed that compound A24 operates by increasing the permeability of bacterial cell membranes, inhibiting biofilm formation and cell motility, and inducing morphological changes in bacterial cells. Importantly, in vivo tests showed its excellent protective and curative effects on rice bacterial leaf streak. Besides, molecular docking showed that the hydrophobic effect and hydrogen-bond interactions are key factors between the binding of A24 and AvrRxo1-ORF1. Therefore, these results suggest the utilization of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures as a bacterial biofilm inhibiting agent, warranting further exploration in the realm of agrochemical development.

Sulfonate derivatives bearing an amide unit: design, synthesis and biological activity studies.

Pest disasters which occurs on crops is a serious problem that not only cause crop yield loss or even crop failure but can also spread a number of plant diseases.Sulfonate derivatives have been widely used in insecticide and fungicide research in recent years. On this basis, a series of sulfonate derivatives bearing an amide unit are synthesized and the biological activities are evaluated. The bioassay results showed that compounds A8, A13, A16, B1, B3, B4, B5, B10, B12 - 20, C3, C5, C9, C10, C14, C15, C17 and C19 showed 100% activity at a concentration of 500 µg/mL against the Plutella xylostella (P. xylostella). Among them, B15 which contains a thiadiazole sulfonate structure still shows 100% activity at 50 µg/mL concentration against P. xylostella and had the lowest median lethal concentration (LC50) (7.61 µg/mL) among the target compounds. Further mechanism studies are conducted on compounds with better insecticidal activity. Molecular docking results shows that B15 formed hydrophobic interactions π-π and hydrogen bonds with the indole ring of Trp532 and the carboxyl group of Asp384, respectively, with similar interaction distances or bond lengths as those of diflubenzuron. Moreover, chitinase inhibition assays are performed to further demonstrate its mode of action. In addition, the anti-bacterial activity of the series of compounds is also tested and the results showed that the series of compounds has moderate biological activity against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), with inhibition rates of 91%, 92% and 92%, 88% at the concentration of 100 µg/mL, respectively. Our study indicates that B15 can be used as a novel insecticide for crop protection.

Zinc Deficiency Exacerbates Behavioral Impediments and Dopaminergic Neuron Degeneration in a Mouse Model of Parkinson Disease.

BACKGROUND: Circulating zinc (Zn) concentrations are lower than normal in patients with Parkinson disease (PD). It is unknown whether Zn deficiency increases the susceptibility to PD. OBJECTIVES: The study aimed to investigate the effect of dietary Zn deficiency on behaviors and dopaminergic neurons in a mouse model of PD and to explore potential mechanisms. METHODS: Male C57BL/6J mice aged 8-10 wk were fed Zn adequate (ZnA; 30 µg/g) or Zn deficient (ZnD; <5 µg/g) diet throughout the experiments. Six weeks later 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected to generate the PD model. Controls were injected with saline. Thus, 4 groups (Saline-ZnA, Saline-ZnD, MPTP-ZnA, and MPTP-ZnD) were formed. The experiment lasted 13 wk. Open field test, rotarod test, immunohistochemistry, and RNA sequencing were performed. Data were analyzed with t-test, 2-factor ANOVA, or Kruskal-Wallis test. RESULTS: Both MPTP and ZnD diet treatments led to a significant reduction in blood Zn concentrations (PMPTP = 0.012, PZn = 0.014), reduced total distance traveled (PMPTP < 0.001, PZn = 0.031), and affected the degeneration of dopaminergic neurons in the substantia nigra (PMPTP < 0.001, PZn = 0.020). In the MPTP-treated mice, the ZnD diet significantly reduced total distance traveled by 22.4% (P = 0.026), decreased latency to fall by 49.9% (P = 0.026), and reduced dopaminergic neurons by 59.3% (P = 0.002) compared with the ZnA diet. RNA sequencing analysis revealed a total of 301 differentially expressed genes (156 upregulated; 145 downregulated) in the substantia nigra of ZnD mice compared with ZnA mice. The genes were involved in a number of processes, including protein degradation, mitochondria integrity, and α-synuclein aggregation. CONCLUSIONS: Zn deficiency aggravates movement disorders in PD mice. Our results support previous clinical observations and suggest that appropriate Zn supplementation may be beneficial for PD.

Blood levels of omega-6 fatty acids and coronary heart disease: a systematic review and metaanalysis of observational epidemiology.

Individual omega-6 polyunsaturated fatty acids (PUFAs), principally linoleic acid (LA) and arachidonic acid (AA), may have differential impacts on cardiovascular risk. We aimed to summarize the up-to-date epidemiology evidence on the relationship between blood levels of omega-6 PUFAs and the risk of coronary heart disease (CHD). Population-based studies determining PUFA levels in blood were identified until May 2021 in PubMed, Embase, Web of Science, and Cochrane Library. Random-effects meta-analyses of cohorts comparing the highest versus lowest category were conducted to combine study-specific risk ratios (RRs) with 95% confidence intervals (CIs). Blood levels of omega-6 PUFAs were compared between the CHD case and non-case, presented as a weight mean difference (WMD). Twenty-one cohorts and eleven case-control studies were included. The WMD was -0.71 (95% CI: -1.20, -0.21) for LA and 0.08 (95% CI: -0.28, 0.43) for AA. LA levels were inversely associated with total CHD risk (RR: 0.85, 95% CI: 0.71, 1.00), but not AA. Each one-SD increase in LA levels resulted in 10% reductions in the risk of fatal CHD (RR: 0.90, 95% CI: 0.86, 0.95), but not in non-fatal CHD. Such findings highlight that the current recommendation for optimal intakes of omega-6 PUFAs (most LA) may offer a coronary benefit in primary prevention.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2056867 .

Intra-Articular Biomechanical Changes of the Meniscus and Ligaments During Stance Phase of Gait Circle after Different Anterior Cruciate Ligament Reconstruction Surgical Procedures: A Finite Element Analysis.

OBJECTIVE: The debate on the superiority of single- or double-bundle for anterior cruciate ligament reconstruction has not ceased. The comparative studies on intra-articular biomechanics after different surgical reconstructions are rare. This study is to evaluate the biomechanical stress distribution intra-knee after single- and double-bundle anterior cruciate ligament reconstruction by three-dimensional finite element analysis, and to observe the change of stress concentration under the condition of vertical gradient loads. METHODS: In this study, magnetic resonance imaging data were extracted from patients and healthy controls for biomechanical analysis. Patients included in the three models were matched in age and sex. The strength and distribution of induced stresses were analyzed in two frequently used procedures, anatomical single-bundle anterior cruciate ligament reconstruction and anatomical double-bundle anterior cruciate ligament reconstruction, using femoral-graft-tibial system under different loads, to mimic a post-operation mechanical motion. The three-dimensional finite-element models for normal ligament and two surgical methods were applied. A vertical force simulating daily walking was performed on the models to assess the interfacial stresses and displacements of intra-articular tissues and ligaments. The evaluation results mainly included the stress of each part of ligament and meniscus. The stress values of different parts of three models were extracted and compared. RESULTS: The stress of ligament/graft at femoral side of three finite-element models was significantly higher than at tibial side, while the highest level was observed in single-bundle reconstruction finite-element model. With the increase of force, the maximum stress in the medial (7.1-7.1 MPa) and lateral (4.9-7.4 MPa) meniscus of single-bundle reconstruction finite-element model shifted from the anterior horn to the central area (p = 0.0161, 0.0479, respectively). The stress was shown to be at a lower level at femoral side and posterior cruciate ligament of intra-knee in two reconstruction finite-element models than that in normal finite-element models, while presented higher level at the tibial side than normal knee (p = 0.3528). The displacement of the femoral side and intra-knee areas in reconstruction finite-element models was greater than that in normal finite-element model (p = 0.0855). CONCLUSION: Compared with the single-bundle technique, the graft of double-bundle anterior cruciate ligament reconstruction has better stress dissipation effect and can prevent postoperative meniscus tear more effectively.

Association of Dietary Intake and Biomarker of α-Linolenic Acid With Incident Colorectal Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

Background and Objective: There is keen interest in better understanding the impacts of alpha-linolenic acid (ALA), a plant-derived n-3 fatty acid, in ameliorating the development of cancer; however, results of several prospective cohorts present an inconsistent association between ALA intake and the incident colorectal cancer (CRC). We aimed to investigate the summary association of dietary intake and biomarkers of ALA with CRC risk based on the prospective cohorts. Methods: Pertinent prospective cohorts were identified in Cochrane Library, PubMed, and EMBASE from inception to February 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) for comparing the top with the bottom quartiles of ALA levels were combined using a random-effects model. Nonlinear dose-response relationships of ALA levels in diet and blood with CRC risk were assessed using the restricted cubic spline models, respectively. Results: Over the duration of follow-up with a median of 9.3 years ranging from 1 to 28 years, 12,239 CRC cases occurred among 861,725 participants from 15 cohorts (11 studies on diet and 5 studies on biomarkers including 4 on blood and 1 on adipose tissue). The summary RR was 1.03 (95% CI: 0.97, 1.10; I2: 0.00%) for dietary intake and 0.83 (95% CI: 0.69, 0.99; I2: 0.00%) for biomarker. Each 0.1% increase in the levels of ALA in blood was associated with a 10% reduction in risk of CRC (summary RR: 0.90, 95% CI: 0.80, 0.99; I2: 38.60%), whereas no significant dose-response association was found between dietary intake of ALA and the incident CRC (p for non-linearity = 0.18; p for linearity = 0.24). Conclusions: Blood levels of ALA were inversely and linearly associated with the risk of CRC, which suggested that increased intake of ALA to improve circulating levels was beneficial for CRC prevention.

[Survey of dentists' knowledge and behavior of medications used during pregnancy in Beijing area].

PURPOSE: To investigate dentists' knowledge and behavior of drugs used during pregnancy in Beijing and analyze sources of influence. METHODS: A cross sectional survey was undertaken among 259 dentists in Beijing. The percentage frequency distributions of correct responses regarding medication safety during pregnancy and the use of drugs were calculated. Logistic regression model was used to explore factors associated with dentists' knowledge of medications used during pregnancy with SAS 9.4 software package. RESULTS: The correct rate on medication safety during pregnancy ranged from 1.93%-57.92%. The percentage of knowledge scores exceeding 8 point was only 10.42% (out of 16 points). In addition, the percentage of drugs prescribed and used during pregnancy was generally low(2.8%-27.09%). CONLUSIONS: Dentists in Beijing do not have sufficient knowledge about medication used during pregnancy. Continuing education is needed and professional authorities should develop unified guidelines to standardize their clinical practice.

[Multi-disciplinary knowledge integration and its technical approaches in the integrated ecology of macroecosystem science]. / å®è§‚ç”Ÿæ€ç³»ç»Ÿç§‘å­¦æ•´åˆç ”ç©¶çš„å¤šå­¦ç§‘çŸ¥è¯†èžåˆåŠå ¶æŠ€æœ¯é€”å¾„.

The development of contemporary macroecosystem sciences requires to comprehensively understand the process mechanism and model mechanism of large-scale macroecosystem structure and function, spatial variation, and dynamic evolution, to realize quantitative simulation, scientific assessment, prediction and early warning of ecosystem change and its impacts on human well-being, and to serve the utilization, protection, regulation, and management of ecosystems. Therefore, a new research field of large-scale integrated ecology of macroecosystem science (IEMES) is emerging. Based on the systematic analysis of the basic theories, approaches and key technologies of integrated ecology of macroecosystem science, the following basic understandings have been formed: 1) IEMES takes macroecosystem at regional, continental, and global scales as the research object, and adopts the methods and technologies of multidisciplinary knowledge integration. It is aimed to solve the major resource and environmental problems during the development of human society, such as food security, resource security, ecological security, and environmental security. 2) The basic scientific and technological tasks of IEMES are to understand the basic structural and functional properties of macroecosystem, monitor the changes of ecosystem state, explain the spatiotemporal evolution of ecosystem, uncover the mechanism of ecosystem operation and maintenance process, quantitatively evaluate the functional state and service capacity of ecosystem, predict the dynamic evolution and geographical pattern of ecosystem, provide early warning of ecosystem changes and ecological environmental disasters. 3) It is needed to reconstruct the theory and methodology system of "multi-source data analysis, multi-model simulation, multi-disciplinary knowledge fusion" and develop key technology of multi-disciplinary knowledge fusion of "multi-scale observation, multi-method verification, multi-process fusion, and cross-scale simulation" for IEMES. 4) The continental scale multi-spatiotemporal ecosystem observation and experiment network is the basic scientific and technological facility to carry out deep integration of multi-disciplinary knowledge. It is necessary to develop key technology of multi-disciplinary ecological knowledge integration of multi-factor, multi-process, multi-interface, multi-medium, multi-scale, and multi-method around the regional, continental, and global scale macroecosystem science issues.

Arsenic induces transgenerational behavior disorders in Caenorhabditis elegans and its underlying mechanisms.

The present study aimed to identify the effects of arsenic on behaviors in Caenorhabditis elegans (C. elegans) and the transgenerational effects. The synchronized C. elegans (P generation) were exposed to 0, 0.2, 1.0, and 5.0 mM NaAsO2 and the subsequent generations (F1 and F2) were maintained on fresh nematode growth medium (NGM). The behaviors and growth were recorded at 0, 12, 24, 36, 48, 60, and 72 h post synchronization. The results demonstrated that arsenic affected various indicators regarding the behavior (head thrash, body bend, movement speed, wavelength, amplitude and so on) and in general the effects started to accumulate from 24 h and lasted throughout the exposure. The behavior impairments were transgenerational with varying patterns, amongst the head thrash and body bend responded most sensitively though the responses gradually declined across generations. Arsenic exposure inhibited the growth (body length, body width, and body area) in P C. elegans from 24 h to 60 h, however there was no difference between treatments groups and the control at 72 h. Arsenic led to a dose-dependent degeneration of dopaminergic neurons in C. elegans, and inhibition of BAS-1 and CAT-2 expressions. The expressions of GCS-1, GSS-1, and SKN-1 were induced by arsenic exposure. Overall, chronic arsenic exposure impaired the behaviors and there were transgenerational effects. The head thrash and body bend responded most sensitively. Arsenic induced behavioral disorders might be attributed to degeneration of dopaminergic neurons which was associated with oxidative stress.

Lowering effects of fish oil supplementation on proinflammatory markers in hypertension: results from a randomized controlled trial.

Reduced inflammation is one of the potential mechanisms underlying the cardioprotective efficacy of fish oil enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Supplementation with fish oil has favorable effects on cardiometabolic profiles in Inner Mongolia patients with hypertension, but whether the cardiovascular benefits can be ascribed to reduced subclinical inflammation is unclear among this population. Seventy-seven middle-aged/elderly hypertensive volunteers were randomly assigned to receive either fish oil (FO, n = 38, 2 g day-1 EPA + DHA) or control corn oil (CO, n = 39) for 90 days. FA compositions in erythrocytes and C-reactive protein (CRP, mg L-1), interleukin-6 (IL-6, pg mL-1) and tumor necrosis factor-α (TNF-α, pg mL-1) concentrations in the plasma were measured before and after the 90-day supplementation, and the cardiometabolic risk was expressed as continuously distributed z-scores calculated by standardizing and then summing the individual cardiovascular risk factors. Significant reductions in the TNF-α (-1.87 ± 2.71 vs. -0.64 ± 2.62, p = 0.02) and CRP levels (-0.85 ± 2.49 vs. 0.56 ± 2.14, p = 0.01) were found in the FO group compared with the CO group, but not in the IL-6 levels (-0.66 ± 1.05 vs. -0.25 ± 0.94, p = 0.10). The decreases in the changes of TNF-α levels were positively correlated with the reductions in the cardiometabolic risk scores in the subjects supplemented with FO (r = 0.35, p = 0.02), but not in the control subjects supplemented with CO (r = 0.09, p = 0.54). FO supplementation increased the levels of EPA (p = 0.013), DHA (p = 0.040) and total n-3 FA (p = 0.035), and decreased the levels of 20:4n-6 (p = 0.041) and total n-6 FA (p = 0.011) and the ratio of n-6 to n-3 FA (p = 0.001), compared with the changes related to the CO group. The increases in the changes of erythrocyte total n-3 FA levels were inversely correlated with the concentrations of TNF-α (r = -0.34, p = 0.001) and CRP (r = -0.29, p = 0.020). The present findings suggest that fish oil supplementation may attenuate the proinflammatory reactions in hypertension, which might help promote the cardiometabolic benefits in this Inner Mongolia population.

Properties of Rigid Polyurethane Foam Modified by Tung Oil-Based Polyol and Flame-Retardant Particles.

Although tung oil is renewable, with an abundant production and low price in China, and it is used to synthesize different polyols for rigid polyurethane foam (RPUF), it remains a challenge to improve the properties of RPUF by redesigning the formula. Therefore, we propose four novel compounds to strengthen the properties of RPUF, such as the catalyst-free synthesis of tung oil-based polyol (PTOK), aluminum phosphate micro-capsule (AM), silica micro-capsule (SiM), and grafted epoxidized monoglyceride of tung oil on the surface of SiO2 (SiE), which were designed and introduced into the RPUF. Because of the PTOK with a catalytic function, the foaming process of some RPUF samples was catalyst-free. The results show that the incorporation of AM, SiM, and SiE, respectively, endow RPUF with a better thermal stability at a high temperature, and the T5%, Tmax1, and Tmax2 of RPUF appeared to be reduced, however, the Tmax3 and residue rate at 800 °C were improved, which may have a positive effect on the extension of the rescue time in case of fire, and the limiting oxygen index (LOI) value was increased to 22.6%. The formula, containing 25% PTOK made the RPUF environment-friendly. The results were obtained by comparing the pore size and mechanical properties of the RPUF-the AM had a better dispersion in the foam, and the foam obtained a better mechanical, thermal, and flame retardancy.

Circulating long-chain n-3 polyunsaturated fatty acid and incidence of stroke: a meta-analysis of prospective cohort studies.

BACKGROUND: Circulating long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) can provide objective measures that reflect both dietary consumption and relevant biological processes. Nevertheless, prospective cohort studies on circulating LC n-3 PUFA in relation to incidence of stroke have yielded inconsistent results. We therefore conducted a meta-analysis to quantitatively evaluate the association. RESULTS: A total of 2,836 stroke events occurred among 20,460 individuals aged 35-79 yr from 10 prospective cohort studies. Circulating LC n-3 PUFA was significantly associated with reduced risk of stroke (RR: 0.86; 95% CI: 0.76, 0.98; I2 = 0.00%), especially 22:5n-3 (RR: 0.74; 95% CI: 0.60, 0.92) and 22:6n-3 (RR: 0.78; 95% CI: 0.65, 0.94). The associations were more pronounced with ischemic stroke (RR: 0.81; 95% CI: 0.68, 0.96), but not with hemorrhagic stroke (RR: 0.95; 95% CI: 0.60, 1.49). A 1% increment of 22:5n-3 and 22:6n-3 proportions in circulating blood was associated with 25% (RR: 0.75; 95% CI: 0.64, 0.87) and 11% (RR: 0.89; 95% CI: 0.83, 0.95) reduced risk of stroke, respectively. MATERIALS AND METHODS: Pertinent studies were identified from Cochrane Library, PubMed and EMBASE database through June 2017. Multivariate-adjusted risk ratios (RRs) with 95% confidence interval (CI) for incident stroke when comparing the top with the bottom tertiles of baseline LC n-3 PUFA proportions in blood were pooled using a random-effect model. CONCLUSIONS: Circulating LC n-3 PUFAs were linearly associated with reduced risk of stroke, especially 22:5n-3 and 22:6n-3. Such findings highlight the importance of circulating LC n-3 PUFA in the development of ischemic stroke.

Effects of ABCDE Bundle on Hemodynamics in Patients on Mechanical Ventilation.

BACKGROUND Mechanical ventilation is an important part of advanced life support in the intensive care unit (ICU). This study aimed to investigate the effects of ABCDE bundle on hemodynamics in patients on mechanical ventilation (MV). MATERIAL AND METHODS This study used a cross-sectional overall controlled approach in which 143 patients on mechanical ventilation were divided into 2 groups. In the pre-ABCDE bundle group (n=70), conventional sedation and analgesia strategy were used. In the post-ABCDE bundle group (n=73), ABCDE bundle was used. Changes in hemodynamics parameters and related prognostic indicators were monitored at various time points before (T0) and at 1 d (T1), 3 d (T3), 5 d (T5), and 7 d (T7) after implementation of the 2 strategies. RESULTS Mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR), and oxygenation index (PaO2/FiO2) in the bundle group were improved more significantly than those in the pre-ABCDE bundle group (P<0.05). For comparison between various monitoring time points in the same group, compared with before intervention, MAP, CVP, HR, and PaO2/FiO2 changed significantly in the bundle group at 3 d, 5 d, and 7 d after intervention, and the difference was statistically significant (P<0.05). Compared with before intervention, differences in all hemodynamics indicators were statistically significant in the pre-ABCDE bundle group at 5 d and 7 d after intervention (P<0.05). Compared with the pre-ABCDE bundle group, differences in prognostic indicators in the post-ABCDE bundle were statistically significant (P<0.05). CONCLUSIONS ABCDE bundle is safe and effective for patients on mechanical ventilation, and can improve hemodynamics and enhance oxygenation index. ABCDE bundle might be helpful in reducing 28-d mortality and improving prognosis.

Hyperoside inhibits lipopolysaccharide-induced inflammatory responses in microglial cells via p38 and NFκB pathways.

Hyperoside (quercetin-3-O-ß-d-galactoside) is an active compound isolated from herbs. Neuroinflammation is a key mechanism involved in neurodegenerative disorders including Parkinson's disease. In this study, we aimed to investigate the potentiality of hyperoside in inhibiting microglia-mediated neuroinflammation. BV2 microglial cells were pretreated with hyperoside and stimulated with lipopolysaccharide (LPS). The results showed that hyperoside significantly inhibited LPS-induced production of nitric oxide and pro-inflammatory cytokines including IL-1ß and TNF-α, as well as the expression of inducible nitric oxide synthase. Similar results were observed in primary microglial cells isolated from neonatal mice. Analyses in MAPK and NFκB signaling combined with specific inhibitors suggested that hyperoside attenuated the LPS-induced inflammatory responses via p38 and NFκB pathways. Furthermore, hyperoside suppressed reactive microglia-mediated neurotoxicity as evidenced by conditioned media culture, but had no direct impact on MPP+-induced toxicity in SH-SY5Y neuroblastoma cells. Collectively, our data suggest that hyperoside may serve as a protective agent by alleviating microglia activation in disorders such as Parkinson's disease.

Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.

Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and KATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the KATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1α, IL-6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI.

A decline of LAMP- 2 predicts ursodeoxycholic acid response in primary biliary cirrhosis.

Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. We have previously reported that augmented expression of lysosome-associated membrane protein 2 (LAMP-2) was correlated with the severity of PBC. This study aimed to determine whether serum LAMP-2 could serve as a predictor of biochemical response to UDCA. The efficiency of serum LAMP-2 to predict biochemical response was assessed after 1 year of UDCA treatment in PBC patients by a retrospective analysis. We found that the basal serum LAMP-2 level was increased in PBC, especially in patients with stage III-IV (p = 0.010) or TBIL > 1 mg/dL (p = 0.014). Baseline serum LAMP-2 was higher in non-responders than that in responders, but the difference was statistically insignificant. However, after UDCA treatment, serum LAMP-2 level decreased prominently in the first 3 months, which was more obvious in responders. Further studies showed that the 35% decline of LAMP-2 after treatment for 3 months could be stated as an indicator of UDCA response with the sensitivity of 62.9% and specificity of 75.0% by Paris criteria. Meanwhile the specificity and sensitivity were identified as 63.5% and 64.1% by Barcelona criteria. Together, a decline in LAMP-2 might help to predict the response to UDCA.

Biospecimen long-chain N-3 PUFA and risk of colorectal cancer: a meta-analysis of data from 60,627 individuals.

BACKGROUND: Several prospective cohort and case-control studies reported the inconsistent association between biospecimen composition of C20 and C22 long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) and colorectal cancer (CRC) risk. The aim of the present study was to investigate the association of biospecimen LC n-3 PUFA with CRC risk based on prospective cohort and case-control studies. METHODS AND RESULTS: Cochrane Library, PubMed, and EMBASE database were searched up to February 2014 for eligible studies. Risk ratios (RRs) or odds ratios (ORs) from prospective and case-control studies were combined using a random-effects model in the highest vs. lowest categorical analysis. Nonlinear dose-response relationships were assessed using restricted cubic spline regression models. Difference in tissue composition of LC n-3 PUFA between cases and noncases was analyzed as standardized mean difference (SMD). Three prospective cohort studies and 8 case-control studies were included in the present study, comprising 60,627 participants (1,499 CRC cases and 59,128 noncases). Higher biospecimen LC n-3 PUFA was significantly associated with a lower risk of CRC in case-control (pooled OR: 0.76; 95% CI: 0.59, 0.97; I2 = 10.00%) and prospective cohort studies (pooled RR: 0.70; 95% CI: 0.55, 0.88; I2 = 0.00%), respectively. A significant dose-response association was found of biospecimen C20:5n-3 (P for nonlinearity  = 0.02) and C22:6n-3 (P for trend  = 0.01) with CRC risk, respectively. Subjects without CRC have significantly higher biospecimen compositions of C20:5n-3 (SMD: 0.27; 95%: 0.13, 0.41), C22:6n-3 (SMD: 0.23; 95%: 0.11, 0.34) and total LC n-3 PUFA (SMD: 0.22; 95% CI: 0.07, 0.37) compared with those with CRC. CONCLUSIONS: The present evidence suggests human tissue compositions of LC n-3 PUFA may be an independent predictive factor for CRC risk, especially C20:5n-3 and C22:6n-3. This needs to be confirmed with more large-scale prospective cohort studies.

Ratio of n-3/n-6 PUFAs and risk of breast cancer: a meta-analysis of 274135 adult females from 11 independent prospective studies.

BACKGROUND: Increased ratio of n-3/n-6 polyunsaturated fatty acids (PUFAs) in diet or serum may have a protective effect on the risk of breast cancer (BC); however, the conclusions from prospective studies are still controversial. The purpose of this study is to ascertain the relationship between intake ratio of n-3/n-6 PUFAs and the risk of BC, and estimate the potential summarized dose-response trend. METHODS: Relevant English-language studies were identified through Cochrane Library, PubMed and EMBASE database till April 2013. Eligible prospective studies reporting the multivariate adjusted risk ratios (RRs) for association of n-3/n-6 PUFAs ratio in diet or serum with BC risk. Data extraction was conducted independently by 2 investigators; disagreements were reconciled by consensus. Study quality was assessed using the Newcastle-Ottawa scale. Study-specific RRs were combined via a random-effects model. RESULTS: Six prospective nested case-control and 5 cohort studies, involving 8,331 BC events from 274,135 adult females across different countries, were included in present study. Subjects with higher dietary intake ratio of n-3/n-6 PUFAs have a significantly lower risk of BC among study populations (pooled RR = 0.90; 95% CI: 0.82, 0.99), and per 1/10 increment of ratio in diet was associated with a 6% reduction of BC risk (pooled RR = 0.94; 95% CI: 0.90, 0.99; P for linear trend = 0.012). USA subjects with higher ratio of n-3/n-6 in serum phospholipids (PL) have a significantly lower risk of BC (pooled RR = 0.62; 95% CI: 0.39, 0.97; I2 = 0.00%; P for metaregression = 0.103; P for a permutation test = 0.100), and per 1/10 increment of ratio in serum PL was associated with 27% reduction of BC risk (pooled RR = 0.73; 95% CI: 0.59, 0.91; P for linear trend = 0.004; P for metaregression = 0.082; P for a permutation test = 0.116). CONCLUSIONS: Higher intake ratio of n-3/n-6 PUFAs is associated with lower risk of BC among females, which implies an important evidence for BC prevention and treatment is by increasing dietary intake ratio of n-3/n-6 PUFA. No firm conclusions from USA populations could be obtained, due to the limited numbers of USA studies.

[Effects of training on plasma content of nitric oxide, endothelin and NO/ET system in rats fed with high methionine diet].

OBJECTIVE: To observe the effects of training on plasma content of NO, ET and NO/ET system in rats fed with high methionine diets. METHODS: Male Wistar rats were randomly divided into normal diet group (CR), high methionine diet group (MR) and high methionine diet plus 90 min swimming group (T+ MR). Rats in MR and T+ MR group were fed with the diet which contained 3%of methionine for eight weeks, but rats in control group were fed with ordinary diet. After breeding for eight weeks homocysteine (Hcy) level, T-NOS, NO and ET were measured. RESULTS: Plasma homocysteine of MR increased twofold as compared with that of CR,whereas plasma NO/ET of MR descended significantly (P < 0.05), suggesting that hyperhomocysteinemia was induced by the high methionine diet, and plasma NO/ET system was out of balance. Plasma homocysteine content of T+ MR obviously descended, plasma T-NOS, NO and NO/ET ascended obviously (P < 0.05) as compared with that of MR, and the above indicators of group T + MR were not different as compared with that of CR (P > 0.05). CONCLUSION: Proper training can descend plasma homocysteine level of rats fed with high methionine diet and better balance between NO and ET to prevent developing of hyperhomocysteinemia.

[Effects of azidothymidine on p33ING1b expression, apoptosis and senescence of TJ905 human glioblastoma cell line].

OBJECTIVES: To investigate the pharmacological effects of azidothymidine (AZT) on p33ING1b expression, senescence and apoptosis of TJ905 glioblastoma cells. METHODS: TJ905 cells were treated with AZT at a serial concentrations of 50, 100 and 200 µmol/L. Semi-quantitative RT-PCR and cytochemical staining of senescence related-galactosidase (sß-Gal) were used to evaluate the expression of p33ING1b mRNA and to label the senescent cells at the 1st, 3rd and 6th generations, respectively. In situ cell death detection and single cell gel electrophoresis were used to detect the apoptosis at the 3rd and 6th generations. RESULTS: AZT induced the expression of p33ING1b mRNA and senescence of the tumor cells of the 1st generation in a dosage and time dependent manner. At the 6th generation, the relative amount of p33ING1b RT-PCR product (1.44±0.23) and sß-Gal labeling index of 200 µmol/L group (45.62±6.74) were significantly higher than those of the 1st (0.95±0.13 and 7.82±2.40) and the 3rd generation cells (1.35±0.23, 26.27±7.17) of the same group, and cells of the same generation in the 50 µmol/L (0.85±0.24, 27.37±6.41) and 100 µmol/L groups (1.23±0.34, 35.49±5.12, P<0.01). There was a significant positive correlation between the p33ING1b mRNA expression and the labeling index of sß-Gal. Pro-apoptotic effects of AZT became obvious at the 6th generation. CONCLUSION: AZT upregulates the expression of p33ING1b, a possible mechanism in regulating senescence and apoptosis of the TJ905 cells.