Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary behaviors.The preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion repair.In the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats.Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws.Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections.Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex.Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats.Following sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury.However,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats.Furthermore,PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recove ry compared with those without Sciatic Functional Index recovery,suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries.This correlation was independent of the sex or strain of the rat.Furthermore,our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths.No chronic hypersensitivity developed in any rat up to 12 weeks.All these data suggest that PEG-fusion repair of transection peripheral nerve injuries co uld have important clinical benefits.

Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively.Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts.While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts,loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively.MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts,but MHCII expression was modestly lower compared to negative control at 21 days postoperatively.We conclude that,while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts,successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts,and produce recovery of sensory/motor functions and voluntary behaviors.Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.

Mitochondrial therapeutics and mitochondrial transfer for neurodegenerative diseases and aging

Mitochondrial dysfunction and neurodegeneration:Progressive neurodegenerative diseases affect a significant proportion of the population;in a single year,there are as many as 276 million disabilities and 9 million deaths as a result of neurological diseases.

Male sex determination： insights into molecular mechanisms

Disorders of sex development often arise from anomalies in the molecular or cellular networks that guide the differentiation of the embryonic gonad into either a testis or an ovary, two functionally distinct organs. The activation of the Y-linked gene Sry （sex- determining region Y） and its downstream target Sox9 （Sry box-containing gene 9） triggers testis differentiation by stimulating the differentiation of Sertoli cells, which then direct testis morphogenesis. Once engaged, a genetic pathway promotes the testis development while actively suppressing genes involved in ovarian development. This review focuses on the events of testis determination and the struggle to maintain male fate in the face of antagonistic pressure from the underlying female programme.

The ATPase activity of molecular chaperone HSP60 is inhibited by immunosuppressant mizoribine

The molecular chaperone HSP60 is a chaperonin homolog of GroEL. We had previously shown that the immunosuppressant mizoribine is bound directly to HSP60 and inhibited its chaperone activity. However, the inhibitory mechanisms of HSP60 by mizoribine have not yet been fully understood. In the present study, we investigated the influence of mizoribine on a folding cycle of HSP60 and co-chaperone HSP10. Our results showed that mizoribine inhibited the folding cycle of HSP60/HSP10. The ATPase activity of HSP60/HSP10 was decreased in the presence of mizoribine and the dissociation of HSP10 from HSP-60 was also decreased by mizoribine. The same functions of GroEL and/or GroES were slightly affected by mizoribine. Based on our findings, we discuss the inhibitory mechanisms of HSP60 by mizoribine.

A Comparison of the Clinical and Molecular Diagnosis of Herpes Simplex Keratitis

Purpose: To compare the clinical and molecular diagnoses of Herpes Simplex Keratitis (HSK). Materials and Methods: Conjunctival swabs (after fluorescein and anaesthetic wash out) and detailed questionnaire data were obtained from 146 participants. Corneal rims and conjunctival epithelial cells were infected with Herpes Simplex Virus (HSV) type 1 or HSV2 and supernatant collected. HSV1;HSV2;Varicella Zoster Virus (VZV) and Adenovirus (ADV) DNA was assessed using two real time Polymerase Chain Reaction (PCR) methods. Results: Of the 146 participants recruited, 54 were clinically diagnosed with typical epithelial lesions and 38 with atypical epithelial lesions, 17 with old inactive HSK and 37 healthy volunteers. HSV1 DNA was detected in 28 (30%) of the 92 participants with clinically suspect HSK. Patients who presented with typical epithelial lesions had a higher positive rate (46%) than those who presented with atypical type lesions (8%), when using primers against the Glycoprotein (Gp) G region of the virus. When the same samples were retested with primers against the GpB region, the positive rate for the typical and atypical cases increased to 52% and 11% respectively. Antiviral use at the time of sampling reduced the rate of PCR positivity by 20% (p < 0.05). ADV DNA was detected in 6% of the typical cases and 8% of the atypical cases. All control participants with no history of HSK were negative for HSV1 DNA. Sample quantity was confirmed by testing for housekeeping control genes, beta-actin and beta-2 macroglobulin. PCR results from in vitro control investigations of HSV1 and 2 infected corneal rims and conjunctival epithelial cells were 100% positive for infected and 100% negative for uninfected samples when assessed using both PCR methods. Conclusions: Clinical diagnosis of typical HSK is not always confirmed by PCR. Concomitant use of an antiviral reduces levels of PCR positivity. Given this and the findings that other ocular surface pathogens may mimic HSK pathology, and that choice of gene amplification region can also affect accurate detection of HSV1 by PCR, we propose the use of a multiplex assay. This would perform PCR using primers spanning a number of different regions within one gene and would also target a number of different viral genes to ensure potentially different HSV1 viral strains or other viruses do not affect the test and lead to disagreements between the clinical and molecular diagnosis of HSK. From these findings, this paper proposes a clinical supportive algorithmic guide to manage such disagreements.

红树林沉积物聚乙烯降解菌的筛选和降解特性

【目的】探究湛江市麻章区红树林沉积物中微生物对聚乙烯(PE)塑料的降解特性,丰富红树林塑料降解菌种类。【方法】在湛江市麻章区红树林的高、中、低潮带随机选取9个样点,并采用五点采样法从红树林表层2~5 cm的沉积物中取样。将采集到的沉积物样本在以聚乙烯为唯一碳源的无机盐培养基中进行富集、分离、纯化,以筛选出能够降解PE的菌株,并通过显微形态分析、分子鉴定等方法确定其种属;通过测定生长曲线、失重率、以及分析官能团变化来验证菌株对PE塑料的降解性能。【结果与结论】从沉积物中共筛选出K1-1、K1-2和K1-3三株PE降解能力较强的菌,分别为威尼斯不动杆菌(Acinetobacter venetianus)、Pseudomonas juntendi和维德曼芽孢杆菌(Bacillus wiedmannii)。在120 d的培养周期中,这些菌株的生长曲线均呈抛物线形态。经三株菌作用后,PE表面生成羟基,并形成氨基和羟基化合物,羟基取代羰基,导致PE表观和内部结构明显改变。经120 d处理后,PE膜的失重率分别为6.42%、5.38%和5.73%,其中K1-1菌株处理后PE塑料的失重率相较于目前报道的红树林沉积物中最高降解效率菌株Bacillus gottheilii处理后塑料的失重率提升3.55%。威尼斯不动杆菌(A.venetianus)在PE塑料降解上具有一定潜力,这丰富了湛江红树林沉积物中PE降解菌的种类,为PE塑料的生物降解提供理论支持。

Understanding the oxidation chemistry of Ti_(3)C_(2)T_(x)(MXene)sheets and their catalytic performances

Transition metal carbides and nitrides(MXenes)nanosheets are attractive two-dimensional(2D)materials,but they suffer from oxidation/degradation issues during storage and/or applications due to their sensitivity to water and oxygen.Despite the great research progress,the exact oxidation kinetics of Ti_(3)C_(2)T_(x)(MXene)and their final products after oxidation are not fully understood.Herein,we systematically tracked the oxidation process of few-layer Ti_(3)C_(2)T_(x) nanosheets in an aqueous solution at room temperature over several weeks.We also studied the oxidation effects on the electrocatalytic properties of Ti_(3)C_(2)T_(x) for hydrogen evolution reaction and found that the overpotential to achieve a current density of 10 mA cm^(-2)increases from 0.435 to 0.877 V after three weeks of degradation,followed by improvement to stabilized values of around 0.40 V after eight weeks.These results suggest that severely oxidized MXene could be a promising candidate for designing efficient catalysts.According to our detailed experimental characterization and theoretical calculations,unlike previous studies,black titanium oxide is formed as the final product in addition to white Ti(IV)oxide and disordered carbons after the complete oxidation of Ti_(3)C_(2)T_(x).This work presents significant advancements in better understanding of 2D Ti_(3)C_(2)T_(x)(MXene)oxidation and enhances the prospects of this material for various applications.

Recent advances in essential oils and their nanoformulations for poultry feed

Antibiotics in poultry feed to boost growth performance are becoming increasingly contentious due to concerns over antimicrobial resistance development.Essential oils(EOs),as natural,plant-derived compounds,have demonstrated antimicrobial and antioxidant properties.EOs may potentially improve poultry health and growth performance when included in poultry feed.Nevertheless,the incorporation of EOs as nutritional additives is hindered by their high volatility,low water solubility,poor intestinal absorption,and sensitivity to environmental conditions.Recently,nanoencapsulation strategies using nanoformulations have emerged as a potential solution to these challenges,improving the stability and bioavailability of EOs,and enabling targeted delivery in poultry feed.This review provides an overview of the antioxidant and antibacterial properties of EOs,the current limitations of their applications in poultry feed,and the recent advancements in nano-engineering to overcome these limitations.Furthermore,we outline the potential future research direction on EO nanoformulations,emphasizing their promising role in advancing sustainable poultry nutrition.

Productivity of Commercial Feedlot Beef Production Significantly Improved by Asparagopsis Bioactives Stabilized in Canola Oil

Research using open-circuit respiration chambers has established that Asparagopsis bioactive compounds stabilized in canola oil (Asp-Oil), delivering a range of inclusion between 34 - 51 mg bromoform (CHBr3)/kg dry matter intake (DMI), inhibits methane (CH4) emissions > 98% in feedlot cattle. In this study, Asp-Oil was fed at 35 mg CHBr3/kg DMI in the feedlot finisher diet under highly replicated and commercially relevant conditions, and adequately powered to confirm differences as low as 3.3% in feed conversion efficiency (FCE). The study also evaluated the effect of Asp-Oil on CH4 production (g/day), carcass and meat-eating qualities, animal health, and food safety. The experiment consisted of 300 Angus-Shorthorn (Bos taurus) steers in 30 pens of 10 and fed a barley-based ration supplemented with canola oil (Control, n = 15), or Asp-Oil (n = 15) for total 81-d, inclusive of 21-d transition to full Asp-Oil and grain inclusion in the finisher ration. Reduction of CH4 was measured using GreenFeed Emissions Monitors (GEM) in a subset of 2 pens in both Control and Asp-Oil. However, 67% of CH4 measurements were recorded below the GEM’s limit of detection. An inhibition range of 58% - 98% was demonstrated by collectively using GEM and preliminary respiration chamber measurements. Asp-Oil improved FCE 7.4% in the finisher diet, and 5.6% across transition and finisher periods. During the transition steps the steers had not yet received their full allocations of grain and Asp-Oil which is responsible for the lower FCE benefits. A 4.1% lower DMI in the finisher period contributed to benefits in FCE with no effect on daily weight gains. Cost of feed and weight gain were reduced $0.35/head/day and $0.23/kg, respectively, in steers receiving Asp-Oil. Residues of Asparagopsis CHBr3 were not detected in any sample and only trace iodide and bromide were detected in livers and kidneys of both Control and Asp-Oil steers at levels safe for human consumption. Steers demonstrated normal rumen development typical of feedlot diets. This study confirms that Asp-Oil safely induces significant productivity benefits and CH4 reductions in feedlot beef production. Commercial adoption of Asparagopsis can benefit feedlot beef production and reduces the climate change contribution of livestock production.

Acceptance of COVID-19 vaccine and its related determinants in Nigeria:An online survey

BACKGROUND Vaccine hesitancy is a major challenge in the fight against the coronavirus disease 2019(COVID-19)pandemic.Identifying the sociodemographic factors associated with vaccine acceptance among Nigerians is crucial for improving vaccine uptake.AIM To assess the acceptance rate of COVID-19 vaccine and its related determinants among Nigerians.METHODS An online cross-sectional survey(observational study)was conducted between February 2021 and May 2021,using a questionnaire hosted on SurveyMonkey.The invitation to take part in the poll was sent out to participants through social networking platforms.A logistic regression was used to determine which sociodemographic factors were associated with vaccine acceptance constructs.RESULTS A total of 1800 persons responded to the survey,a larger proportion of whom were males(53.9%)and within the age group of 21-30 years(29.4%)and earned an average income of less than$500 per month(43.3%).Only 0.56%of participants had a high perceived risk of COVID-19 infection,while only 1.11%had a perceived risk of dying from COVID-19.The perception rate of the COVID-19 vaccine among participants was 51.1%,while the acceptance rate was 63.9%.There was no significant association between the COVID-19 vaccine acceptance rate and related determinants assessed,particularly age(χ²=3.049,P=0.550),sex(χ²=0.102,P=0.749),average income(χ²=3.802,P=0.875),and religion(χ²=2.819,P=0.420).Participants with chronic conditions demonstrated a higher acceptance rate compared to the general population.CONCLUSION Despite the positive perception observed and substantial vaccine acceptance rate among the study participants,more public health interventions are still needed to enhance vaccine acceptability in Nigeria.

利用棋盘格实验直接筛选酶免疫测定的最佳包被抗原和抗体浓度

以两个单克隆抗体及其相应的包被抗原为例,研究了棋盘格实验中包被抗原与抗体浓度组合对免疫检测中0孔吸光度值A0、IC50值和标准曲线斜率的影响。结果发现,A0和IC50值随包被抗原与抗体稀释倍数的增加而降低;斜率随抗体稀释倍数增加而降低,而随包被抗原的稀释倍数增加表现出先增加后降低的趋势。在同一抗体浓度和不同包被抗原浓度的组合中,斜率最大值出现在使板吸附达到饱和的最大稀释倍数的包被抗原浓度附近。综合实验结果确认从棋盘格实验中直接筛选最佳包被抗原、抗体浓度组合的标准是:选择使板吸附达到饱和的最大包被抗原稀释倍数为最佳包被抗原浓度,在不同抗体浓度与已选择的最佳包被抗原浓度组合中使0孔吸光度值达1.0左右的抗体稀释倍数为最佳抗体浓度。

植物环蛋白的结构

简要介绍了植物环蛋白的定义、结构特点、研究历史、分布、提取分离方法、化学合成与生物合成、生物活性与生物功能。并主要以从紫花蔓地丁(Viola labridorica)中分离得到的六个环蛋白之一,cy-cloviolacinO2为例介绍通过还原酶解-质谱与二维核磁共振谱结合鉴定环蛋白结构的研究方法。

沙尘PM_(10)质量浓度与气温的关系初探

利用甘肃民勤自动气象站观测的2004～2006年夏季的5 min一次的气温与沙尘PM10浓度资料,通过将数据分为实验组与对照组,研究了气温与沙尘天气之间的统计关系。个例显示,气温与沙尘PM10浓度之间存在降温、升温和混合型3种对应关系。实验组统计分析表明,气温及其变化(每5min间隔气温变化绝对值和每24 h间隔气温变化绝对值)与沙尘PM10浓度及其变化呈现出非常显著的正相关关系;沙尘暴天气下日平均气温变化与相应沙尘PM10浓度变化呈显著负相关。对照组结果表明,实验组统计关系是非常显著的。

大鼠海马神经干细胞的扩增及与三维微小凹图式复合的研究

目的比较2种培养基下海马神经干细胞(neural stem cells,NSCs)的生长特性,进而实现海马NSCs扩增的优化及其与聚乳酸(poly-L-lactide,PLLA)三维微小凹图式的复合。方法分离大鼠胚胎海马细胞并采用Neurobasal为基础的培养基和DMEM/F12为基础的培养基进行扩增。以四甲基氮唑蓝(MTT)比色法及神经球数目统计法评价2种培养基下细胞增殖行为。采用紫外光光刻、硅蚀刻及软光刻技术制备PLLA三维微小凹图式并实现海马NSCs与微小凹图式的复合。结果原代分离的海马细胞呈神经干细胞标志物阳性并能向神经元系和胶质细胞系分化。在30d的扩增时间内,海马NSCs在以Neurobasal为基础的培养基中缓慢扩增聚集成神经球,少见细胞贴壁及分化;在以DMEM/F12为基础的培养基中海马NSCs扩增迅速,但易贴壁和分化。培养第25天时后者神经球数量为前者的4.7倍。微加工制备的微小凹图式结构清晰、稳定,具有高纵横结构比(≥1)。扩增的海马NSCs能在三维微小凹图式上成功复合生长。结论以DMEM/F12为基础的培养基有利于大鼠海马NSCs的扩增,以Neurobasal为基础的培养基利于海马NSCs的纯化。序贯应用2种培养基可有效扩增海马NSCs并实现其与三维微小凹图式的复合。

发展中国家的可再生能源:沼气的机遇和挑战

能源对于现代社会至关重要,是社会经济发展最重要的指标之一。尽管科技不断发展,但仍然有约30亿人(主要集中在发展中国家的农村地区),继续通过在传统的炉灶中燃烧生物质资源(如柴薪、秸秆、动物粪便)的方式来满足烹饪的能源需求。这种方式对环境、社会、经济、公众健康都带来极大负面影响。这些地区要实现可持续性发展,开发干净清洁、价格低廉的可再生能源就势在必行。把现有的生物质资源(动物粪便、秸秆、餐厨垃圾、绿色废弃物)提炼成更加清洁高效的能源载体(例如厌氧发酵产生的沼气),不仅具有提供清洁、可靠能源的独特潜力,同时又能保护当地和全球的环境。尽管沼气对发展中国家来说意义重大,但其面临着成本高、设备安装和维护专业知识缺乏等问题,因而在地理位置分散的社区难以广泛推广应用。因此,政府和非政府层面的通力协作就显得至关重要,从而促进沼气技术的更新改造和传播,开发尚未被开发的潜力。文章旨在通过分析沼气技术的现状、挑战和潜力,明确它在发展中国家未来的研究方向和发展传播路径。

基于核苷酸测序揭示辣椒CMS线粒体基因组结构变异

背景:胞质雄性不育(CMS)是由于线粒体基因组突变导致无功能性花粉产生的一种现象。对CMS和非CMS线粒体基因组的比较分析,揭示线粒体基因组间结构差异及因重组导致的广泛性重排具有重要意义。然而,在辣椒中与CMS相关的线粒体基因组结构及DNA重排机制仍不清楚。结果:获得了辣椒CMS FS4401(507 452 bp)和可育系Jeju(511 530 bp)线粒体完全基因组序列。并对辣椒、烟草线粒体基因组进行了比较分析,发现其均存在广泛的DNA重排和低保守性的非编码DNA区。FS4401和Jeju线粒体基因组比较发现,除了FS4401线粒体基因组中多了一个atp6(ψatp6-2)基因拷贝外,线粒体所有蛋白编码基因都一致。在基因组结构方面,发现两个线粒体基因组上的18个同线性序列区在基因组上存在重排,这些同线性序列区之间的序列总长度分别为30 380(FS4401)和17 847 bp(Jeju)。此前报道的CMS候选基因、orf507和ψatp6-2均位于FS4401最大特异序列片段的边界,在此区间大量的短序列片段聚集在一起,而Jeju中这些短序列表现为缺失或存在于不同的位点。连接序列片段的重复序列和重叠序列(由少数几个核苷酸组成)暗示同源重组导致的广泛性重排可能涉及到该区段的序列进化。本研究还利用其他植物种类的线粒体DNA序列进行分析,揭示CMS相关基因DNA区段的共同特征。结论:辣椒CMS和雄性可育系线粒体基因组大部分序列表现出一致性,但存在大量的基因组重排现象。辣椒CMS候选基因位于高度重排的CMS特定DNA区域的边界或重复序列附近。通过对其他物种CMS相关基因的特征分析,揭示出可能涉及到CMS相关基因进化的共同机制。

Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination?

Alcohol consumption is the principal factor in thepathogenesis of chronic liver diseases.Alcoholic liver disease(ALD)is defined by histological lesions on the liver that can range from simple hepatic steatosis to more advanced stages such as alcoholic steatohepatitis,cirrhosis,hepatocellular carcinoma and liver failure.As one of the oldest forms of liver injury known to humans,ALD is still a leading cause of liver-related morbidity and mortality and the burden is exerting on medical systems with hospitalization and management costs rising constantly worldwide.Although the biological mechanisms,including increasing of acetaldehyde,oxidative stress with induction of cytochrome p4502E1,inflammatory cytokine release,abnormal lipid metabolism and induction of hepatocyte apoptosis,by which chronic alcohol consumption triggers serious complex progression of ALD is well established,there is no universally accepted therapy to prevent or reverse.In this article,we have briefly reviewed the pathogenesis of ALD and the molecular targets for development of novel therapies.This review is focused on current therapeutic strategies for ALD,including lifestyle modification with nutrition supplements,available pharmacological drugs and new agents that are under development,liver transplantation,application of complementary medicines,and their combination.The relevant molecular mechanisms of each conventional medication and natural agent have been reviewed according to current available knowledge in the literature.We also summarized efficacy vs safety on conventional and herbal medicines which are specifically used for the prevention and treatment of ALD.Through a system review,this article highlighted that the combination of pharmaceutical drugs with naturally occurring agents may offer an optimal management for ALD and its complications.It is worthwhile to conduct large-scale,multiple centre clinical trials to further prove the safety and benefits for the integrative therapy on ALD.

Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats

AIM To investigate protective effects and molecular mechanisms of green tea polyphenols(GTP) on nonalcoholic fatty liver disease(NAFLD) in Zucker fatty(ZF) rats.METHODS Male ZF rats were fed a high-fat diet(HFD) for 2 wk then treated with GTP(200 mg/kg) or saline(5 m L/kg) for 8 wk, with Zucker lean rat as their control. At the end of experiment, serum and liver tissue were collected for measurement of metabolic parameters, alanine aminotransferase(ALT) and aspartate aminotransferase(AST), inflammatory cytokines and hepatic triglyceride and liver histology. Immunoblotting was used to detect phosphorylation of AMP-activated protein kinase(AMPK) acetyl-Co A carboxylase(ACC), and sterol regulatory element-binding protein 1c(SREBP1c). RESULTS Genetically obese ZF rats on a HFD presented with metabolic features of hepatic pathological changes comparable to human with NAFLD. GTP intervention decreased weight gain(10.1%, P = 0.052) and significantly lowered visceral fat(31.0%, P < 0.01). Compared with ZF-controls, GTP treatment significantly reduced fasting serum insulin, glucose and lipids levels. Reduction in serum ALT and AST levels(both P < 0.01) were observed in GTP-treated ZF rats. GTP treatment also attenuated the elevated TNFα and IL-6 in the circulation. The increased hepatic TG accumulation and cytoplasmic lipid droplet were attenuated by GTP treatment, associated with significantly increased expression of AMPK-Thr172(P < 0.05) and phosphorylated ACC and SREBP1c(both P < 0.05), indicating diminished hepatic lipogenesis and triglycerides out flux from liver in GTP treated rats. CONCLUSION The protective effects of GTP against HFD-induced NAFLD in genetically obese ZF rats are positively correlated to reduction in hepatic lipogenesis through upregulating the AMPK pathway.