Neonatal hypoxic-ischemic encephalopathy is a serious neurological disease,often resulting in long-term neurodevelopmental disorders among surviving children.However,whether these neurodevelopmental issues can be pass...Neonatal hypoxic-ischemic encephalopathy is a serious neurological disease,often resulting in long-term neurodevelopmental disorders among surviving children.However,whether these neurodevelopmental issues can be passed to offspring remains unclear.The right common carotid artery of 7-day-old parental-generation rats was subjected to permanent ligation using a vessel electrocoagulator.Neonatal hypoxic-ischemic rat models were established by subjecting the rats to 8%O2–92%N2 for 2 hours.The results showed that 24 hours after hypoxia and ischemia,pathological damage,cerebral atrophy,liquefaction,and impairment were found,and Zea-Longa scores were significantly increased.The parental-generation rats were propagated at 3 months old,and offspring were obtained.No changes in the overall brain structures of these offspring rats were identified by magnetic resonance imaging.However,the escape latency was longer and the number of platform crossings was reduced among these offspring compared with normal rats.These results indicated that the offspring of hypoxic-ischemic encephalopathy model rats displayed cognitive impairments in learning and memory.This study was approved by the Animal Care&Welfare Committee of Kunming Medical University,China in 2018(approval No.kmmu2019072).展开更多
Illicit and pharmaceutical drugs are considered to be emerging contaminants of concern,and much research effort has gone into assessing their occurrence in wastewater.However,little information exists on their presenc...Illicit and pharmaceutical drugs are considered to be emerging contaminants of concern,and much research effort has gone into assessing their occurrence in wastewater.However,little information exists on their presence in treated sludge or biosolids.In this study,we examined sludge and biosolids from a large metropolitan wastewater treatment plant(WWTP)in Australia to determine the occurrence of five drugs of abuse,including benzoylecgonine as indicator of cocaine consumption,methamphetamine and 3,4-methylenedioxy methamphetamine(MDMA)as representative illicit stimulants,and codeine and morphine as pharmaceuticals with potential environmental risk.The samples were solid-phase extracted and analyzed by liquid chromatography–tandem mass spectrometry(LC–MS/MS).Benzoylecgonine and MDMA were present in raw sludge but were notably degraded during solids treatment processes,and were not detected in the dewatered sludge(after treatment)or in biosolids.Methamphetamine,codeine,and morphine were detected in all biosolids samples at mean concentrations of 20–50 lg kg^-1.The presence of these three drugs in biosolids shows that these compounds are relatively stable in the solids and in soil,and can persist in biosolids for at least several years.A simple environmental risk assessment based on estimated risk quotients(RQs)for these compounds indicated that the potential environmental risks associated with the land application of biosolids are very low at typical Australian biosolids application rates.展开更多
A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neona...A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neonatal hypoxic-ischemic brain damage remain elusive.Seven-day-old rats were used to establish a hypoxic ischemic encephalopathy model.SNPs and expression profiles of mRNAs were analyzed in hypoxic ischemic encephalopathy model rats using RNA sequencing.Genes exhibiting SNPs associated with hypoxic ischemic encephalopathy were identified and studied by gene ontology and pathway analysis to identify their possible involvement in the disease mechanism.We identified 89 up-regulated genes containing SNPs that were mainly located on chromosome 1 and 2.Gene ontology analysis indicated that the up-regulated genes containing SNPs are mainly involved in angiogenesis,wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels.Signaling pathway analysis indicated that the differentially expressed genes play a role in glutamatergic synapses,long-term depression and oxytocin signaling.Moreover,intersection analysis of high throughput screening following PubMed retrieval and RNA sequencing for SNPs showed that CSRNP1,DUSP5 and LRRC25 were most relevant to hypoxic ischemic encephalopathy.Significant up-regulation of genes was confirmed by quantitative real-time polymerase chain reaction analysis of oxygen-glucose-deprived human fetal cortical neurons.Our results indicate that CSRNP1,DUSP5 and LRRC25,containing SNPs,may be involved in the pathogenesis of hypoxic ischemic encephalopathy.These findings indicate a novel direction for further hypoxic ischemic encephalopathy research.This animal study was approved on February 5,2017 by the Animal Care and Use Committee of Kunming Medical University,Yunnan Province,China(approval No.kmmu2019038).Cerebral tissue collection from a human fetus was approved on September 30,2015 by the Ethics Committee of Kunming Medical University,China(approval No.2015-9).展开更多
AIM To determine the clinical and dietary predictors of common carotid artery intima media thickness(CCA IMT) in a cohort of subjects with type 1 and type 2 diabetes. METHODS Participants with type 1(n = 23) and type ...AIM To determine the clinical and dietary predictors of common carotid artery intima media thickness(CCA IMT) in a cohort of subjects with type 1 and type 2 diabetes. METHODS Participants with type 1(n = 23) and type 2 diabetes(n = 127) had mean and mean maximum CCA IMT measured using B mode ultrasound. Dietary intake was measured using a food frequency questionnaire. Clinical and dietary predictors of mean and mean maximum CCA IMT were determined using linear regression analysis adjusted for potential confounders. RESULTS The main predictors of mean and mean maximum CCA IMT were age and weight. After multivariate adjustment there were no dietary predictors of CCA IMT. However,in subjects that were not prescribed a lipid lowering medication alcohol consumption was positively associated with CCA IMT after multivariate adjustment. No difference existed in CCA IMT between subjects with type 1 or type 2 diabetes once age was adjusted for. CONCLUSION CCA IMT was predominantly predicted by age and weight in these subjects with diabetes. The finding that CCA IMT was not different between people with type 1 and type 2 diabetes warrants further investigation in a larger cohort.展开更多
AIM To discuss type 2 diabetes mellitus(T2DM) medication changes required during the popular 5:2 intermittent energy restriction(IER) diet. METHODS A search was conducted in MEDLINE, EMBASE, AMED, CINAHL and Cochrane ...AIM To discuss type 2 diabetes mellitus(T2DM) medication changes required during the popular 5:2 intermittent energy restriction(IER) diet. METHODS A search was conducted in MEDLINE, EMBASE, AMED, CINAHL and Cochrane library for original research articles investigating the use of very low calorie diets(VLCD) in people with T2 DM. The search terms used included "VLCD" or "very low energy diet" or "very low energy restriction" or "IER" or "intermittent fasting" or "calorie restriction" or "diabetes mellitus type 2" and "type 2 diabetes". Reference lists of selected articles were also screened for relevant publications. Only research articles written in English, which also included an explanation of medication changes were included. A recent pilot trial using the 5:2 IER method, conducted by our research group, will also be summarized.RESULTS A total of 8 studies were found that investigated the use of VLCD in T2 DM and discussed medication management. Overall these studies indicate that the use of a VLCD for people with T2 DM usually require the cessation of medication to prevent hypoglycemia. Therefore, the 5:2 IER method will also require medication changes, but as seen in our pilot trial, may not require total cessation of medication, rather a cessation on the 2 IER days only. CONCLUSION Guidelines outlined here can be used in the initial stages of a 2-d IER diet, but extensive blood glucose monitoring is still required to make the necessary individual reductions to medications in response to weight loss.展开更多
Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, how...Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, however, whether such early gestational and/or lactational exposure can influence the later adult-type Leydig cell phenotype. In this study, Sprague-Dawley rats were exposed to dibutyl phthalate （DBP; from gestational day （GD） 14.5 to postnatal day （PND） 6） or diethylstilbestrol （DES; from GD14o5 to GD16.5） during a short gestationalllactational window, and male offspring subsequently analysed for various postnatal testicular parameters. All offspring remained in good health throughout the study. Maternal xenobiotic treatment appeared to modify specific Leydig cell gene expression in male offspring, particularly during the dynamic phase of mid-puberty, with serum INSL3 concentrations showing that these compounds led to a faster attainment of peak values, and a modest acceleration of the pubertal trajectory. Part of this effect appeared to be due to a treatment-specific impact on Leydig cell proliferation during puberty for both xenobiotics. Taken together, these results support the notion that maternal exposure to certain xenobiotics can also influence the development of the adult-type Leydig cell population, possibly through an effect on the Leydig stem cell population.展开更多
AIM： To investigate the relationship between 90-kuD ribosomal $6 kinase （pg0RSK） and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro.METHODS： Rat hepatic fibrosis was ind...AIM： To investigate the relationship between 90-kuD ribosomal $6 kinase （pg0RSK） and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro.METHODS： Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type I were determined by co-immunofluoresence and confocal microscopy.Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell （HSC） line. The expression of collagen type I in HSC-T6 cells was assessed by Western blotting and real-time polymerase chainreaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, thencollagen type I promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated withor without platelet-derived growth factor （PDGF）-BB at a final concentration of 20μg/L and the cell growthwas determined by MTS conversion.RESULTS： In fibrotic liver tissues, p90RSK was over-expressed in activated HSCs and had a significantpositive correlation with collagen type I levels.In HSC-T6 cells transfected with RNAi targeted top90RSK, the expression of collagen type I was down-regulated （61.8% in mRNA, P 〈 0.01, 89.1% inprotein, P 〈 0.01）. However, collagen type ] promoteractivity was not increased with over-expression of p90RSK and not decreased with low expression either,compared with controls in the same cell line （P = 0.076）.Furthermore, p90RSK siRNA exerted the inhibitionof HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation.CONCLUSION： p90RSK is over-expressed in activatedHSCs and involved in regulating the abnormalexpression of collagen type I through initiating theproliferation of HSCs.展开更多
This review will examine topical issues in weight loss and weight maintenance in people with and without diabetes. A high protein, low glycemic index diet would appear to be best for 12-mo weight maintenance in people...This review will examine topical issues in weight loss and weight maintenance in people with and without diabetes. A high protein, low glycemic index diet would appear to be best for 12-mo weight maintenance in people without type 2 diabetes. This dietary pattern is currently beingexplored in a large prevention of diabetes intervention. Intermittent energy restriction is useful but no better than daily energy restriction but there needs to be larger and longer term trials performed. There appears to be no evidence that intermittent fasting or intermittent severe energy restriction has a metabolic benefit beyond the weight loss produced and does not spare lean mass compared with daily energy restriction. Meal replacements are useful and can produce weight loss similar to or better than food restriction alone. Very low calorie diets can produce weight loss of 11-16 kg at 12 mo with persistent weight loss of 1-2 kg at 4-6 years with a very wide variation in long term results. Long term medication or meal replacement support can produce more sustained weight loss. In type 2 diabetes very low carbohydrate diets are strongly recommended by some groups but the long term evidence is very limited and no published trial is longer than 12 mo. Although obesity is strongly genetically based the microbiome may play a small role but human evidence is currently very limited.展开更多
AIM: To examine the effect of increasing dietary zinc (Zn) intake and the lack of metallothionein (MT) expression on activity of small intestinal disaccharidases. METHODS: MT-Ⅰ and Ⅱ knockout (MT-/-) and wild-type (...AIM: To examine the effect of increasing dietary zinc (Zn) intake and the lack of metallothionein (MT) expression on activity of small intestinal disaccharidases. METHODS: MT-Ⅰ and Ⅱ knockout (MT-/-) and wild-type (MT+/+) female mice at 3.5 wk of age were randomly fed with a diet containing 2 (2 Zn), 15 (15 Zn) or 50 (50 Zn) mg Zn/kg (n = 8/group/genotype) for 5 wk. Small intestinal segments (duodenum, jejunum and ileum) were collected and either fixed in 10% formalin for histological analysis or snap frozen in liquid nitrogen for sucrase, lactase and maltase activity analyses.RESULTS: Plasma Zn was significantly (P < 0.05) lower (33%) in MT-/- compared with MT+/+ mice fed the 2 Zn diet. Villus height and crypt depth were increased by approximately 15% in MT+/+ mice compared with MT-/- mice. Duodenal disaccharidase activities were significantly higher in MT+/+ compared with MT-/- mice particularly in those fed the 2 Zn diet. For the 50 Zn diet, jejunal sucrase and lactase activities were significantly higher in MT-/- (13 313 ± 2314; 4107 ± 364 μmol glucose/well/min/g tissue, respectively) compared with MT+/+ mice (7054 ± 608; 1818 ± 174). Similarly, ileal lactase activities were higher in MT-/- (1480 ± 192) compared with MT+/+ (629 ± 353) mice particularly those fed the 2 Zn diet. CONCLUSION: Increasing dietary Zn has little effect on disaccharidases activity in MT wild-type mice. The presence of MT may enhance morphological and functional development of the gut.展开更多
AIM To determine lipid species that change in response to a change in dairy consumption. In addition, to investigate whether dairy associated lipid species are correlated with changes in measures of vascular structure...AIM To determine lipid species that change in response to a change in dairy consumption. In addition, to investigate whether dairy associated lipid species are correlated with changes in measures of vascular structure and function.METHODS A 12-mo randomised controlled trial was conducted to determine the effect of increased consumption of fruit, vegetables and dairy, compared to usual diet, on measures of vascular structure and function in adults with type 1 and type 2 diabetes(n = 108). Thispaper comprises post-hoc analyses investigating the relationship between dairy intake, serum lipid species and vascular health. Central and peripheral blood pressure, carotid femoral pulse wave velocity, augmentation index, serum lipid species and dietary intake were measured at baseline and 3-mo. Common carotid artery intima media thickness was measured at baseline and 12-mo.RESULTS Serum lipid species [lysophosphatidylcholine(LPC) 14:0, LPC 15:0, LPC 16:1, phosphatidylcholine(PC) 29:0 PC 30:0, PC 31:0 and cholesterol ester(CE) 14:0] were associated with the change in full fat dairy consumption(rho 0.19-0.25; P < 0.05). The 3-mo change in some lipids was positively associated with the 3-mo change in central systolic [LPC 14:0(rho 0.30; P = 0.007), PC 30:0(rho 0.28; P = 0.010)] and diastolic blood pressure [LPC 14:0(rho 0.32; P = 0.004), LPC 15:0(rho 0.23; P = 0.04), LPC 16:1(rho 0.23; P = 0.035), PC 29:0(rho 0.28; P = 0.01), PC 30:0(rho 0.36; P = 0.001), PC 31:0(rho 0.30; P = 0.007)] and 12-mo change in common carotid artery intimal medial thickness [CE 14:0(rho 0.22; P = 0.02)]. Pulse wave velocity and augmentation index were unrelated to dairy and lipid species.CONCLUSION An increase in dairy associated lipids appears to be associated with an increase in blood pressure and common carotid intimal medial thickness.展开更多
Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of...Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose ^13 C sodium acetate（^13C-acetate）, which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of ^13CO2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT L100-55 on gelatin capsules and also on DRcaps. Test results demonstrated that DRcaps coated with EUDRAGIT L100-55 possessed enhanced enteric-protective properties, particularly in vivo. These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.展开更多
Morphology-based studies have suggested a very depauperate bee fauna for islands in the South West Pacific, and recent genetic studies since have indicated an even smaller endemic fauna with many bee species in this r...Morphology-based studies have suggested a very depauperate bee fauna for islands in the South West Pacific, and recent genetic studies since have indicated an even smaller endemic fauna with many bee species in this region resulting from human-aided dispersal. These introduced species have the potential to both disrupt native pollinator suites as well as augment crop pollination, but for most species the timings of introduction are unknown. We examined the distribution and nesting biology of the long-tongued bee Braunsapis puangensis that was first recorded from Fiji in 2007. This bee has now become widespread in Fiji and both its local abundance and geographical range are likely to increase dramatically. The impacts of this invasion are potentially enormous for agriculture and native ecosystems, but they also provide opportunities for understanding how social insect species adapt to new environments. We outline the major issues associated with this recent invasion and argue that a long-term monitoring study is needed.展开更多
The functional role of aldehyde dehydrogenases(ALDHs)in prostate cancer remains an area of some controversy.Many studies have used high ALDH functional activity to isolate putative cancer stem cells with tumour-initia...The functional role of aldehyde dehydrogenases(ALDHs)in prostate cancer remains an area of some controversy.Many studies have used high ALDH functional activity to isolate putative cancer stem cells with tumour-initiating and propagating properties,while evidence is also emerging about the involvement of specific isoforms in migration,invasiveness and metastasis.Identification of specific ALDH isoforms,which contribute to both drug resistance and aggressiveness of the disease remains a challenge within the complex heterogeneity of prostate cancer.The purpose of this perspective is to dissect functional roles for ALDH in the tumour microenvironment and to evaluate the potential of the ALDH gene family as biomarkers and/or targets for therapeutic intervention.展开更多
Vaccines are an integral part of veterinary disease prevention. However there are still a significant number of veterinary diseases for which vaccines do not currently exist or where currently available vaccines do no...Vaccines are an integral part of veterinary disease prevention. However there are still a significant number of veterinary diseases for which vaccines do not currently exist or where currently available vaccines do not provide adequate immunity. Adenoviruses have transitioned from tools for gene replacement therapy to bona fide vaccine delivery vehicles because of their ability to elicit potent cell-mediated and humoral responses making them ideal for use against viruses and other intracellular pathogens. Adenoviral vector based vaccines are likely to play a significant role in overcoming these problems in the future. However, this vector is under utilized in veterinary vaccine development at this time. This review focuses on adenoviral vector based vaccines developed to date and explores the potential for veterinary vaccine development based upon this platform: advantages and potential disadvantages of this technology are discussed as well as the potential for developing efficacious commercial veterinary adenoviral vector based vaccines.展开更多
Accurately measuring inspection time (IT) with computers requires several considerations. They are: 1) Screen redraw period;2) Synchronous and timely image presentation;3) Stimulus duration timing;4) Image scale invar...Accurately measuring inspection time (IT) with computers requires several considerations. They are: 1) Screen redraw period;2) Synchronous and timely image presentation;3) Stimulus duration timing;4) Image scale invariance;5) Stan dardized presentation format (of which image scale invariance is a part). The first consideration dictates a minimum duration available for measuring IT. The second and third are necessary for accurate stimulus duration. The fourth is necessary to provide scale invariant images, that is, images with the same visual angle at a given viewing distance on any computer. And the fifth ensures that participants everywhere respond to the same task. Our computer program em bodies these elements and we make it freely available to any interested party. Data to establish validity and reliability are presented, and normative data on 2518 participants aged 6 to 92 years are available.展开更多
Although intensive interventions with low carbohydrate diets compared with higher carbohydrate diets can reduce HbA1c in people with type 2 diabetes, it is not clear if simple advice to make modest reductions in carbo...Although intensive interventions with low carbohydrate diets compared with higher carbohydrate diets can reduce HbA1c in people with type 2 diabetes, it is not clear if simple advice to make modest reductions in carbohydrate is effective in clinical practice. Forty-three people with type 2 diabetes and poor control (HbA1c > 7.5%) were randomized to receive 2 short education sessions over 6 months with a non-dietitian researcher on how to reduce carbohydrate intake by about 25% or to 2 control sessions in which the Australian Guide to Healthy Eating was provided. Hba1c and fasting glucose and lipids were measured at baseline and 3 months and 6 months. 33 volunteers attended a baseline visit;27 completed 3 months and 24 6 months. HbA1c was reduced by 0.6% - 0.7% in the low carbohydrate diet group compared with the control group (P = 0.1). Fasting glucose was reduced by 2.3 mmol/L compared with the control group at 3 months (P < 0.03) only. Changes in HbA1c at 6 months were related to baseline HbA1c in the intervention group only. Although we have obtained suggestive evidence that a low carbohydrate diet can be successfully implemented in normal practice without professional help, our results are limited by low participant numbers and further studies are required.展开更多
BACKGROUND： Spring water therapies have been used since at least 1550 BC. Despite the growing body of evidence supporting these therapies for a range of conditions, including musculoskeletal, dermatological, respirat...BACKGROUND： Spring water therapies have been used since at least 1550 BC. Despite the growing body of evidence supporting these therapies for a range of conditions, including musculoskeletal, dermatological, respiratory and cardiovascular conditions, they do not currently form part of mainstream healthcare in many countries. The protocol established in this paper aims to support systematic reviews that examine the health outcomes associated with human exposure to regional spring waters, using the Australia and New Zealand context as a case study. METHODS/DESIGN： The protocol searches for studies in eight health/medical databases, searches three local health/medical journals, and includes forwards and backwards searching. Standard systematic review methods are used including： specifying pre-deterrnined inclusion criteria and data management plans, appraising the studies for bias, and allocation to a hierarchy of evidence. DISCUSSION： The protocol supports a review and comprehensive synthesis of the current evidence regarding the health effects of natural spring water, and can be adapted for reviews in other regions. From this evidence, recommendations regarding practice and future research can be made on the therapeutic role of spring water.展开更多
The degradation of flavonol glycosides extracted from Ginkgo biloba was performed under different conditions and the degraded products were determined by reversed-phase high performance liquid chromatography （RP-HPLC...The degradation of flavonol glycosides extracted from Ginkgo biloba was performed under different conditions and the degraded products were determined by reversed-phase high performance liquid chromatography （RP-HPLC） method.Four stress conditions including acid（0.1 mol/L HCl）,base（0.1 mol/L NaOH）,temperature （70 ℃） and oxidation（0.03% H2O2,volume fraction） were used for the forced degradation studies.The pH stabilities of the flavonol glycosides were determined in phosphate buffers of varying pH values from 4.5 to 7.4.The degradation rate constants and half-life of three Ginkgo flavonol aglycones（quercetin,kaempferol and isorhamnetin） which represent Ginkgo flavonol glycosides were calculated in forced degradation and pH-stability studies of them.The resuits indicate that the three substances were more stable when incubated under acid condition and showed pH-dependent stability.The degradation was observed to follow first-order kinetics in all degradation studies.The stability results could provide important bases on development,preparation and storage of products of Ginkgo biloba extract and should be significantly considered during the further formulation development.展开更多
The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a s...The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a significant pathomechanism in AD,supported by results of recent clinical trials using anti-Aβantibodies.Nonetheless,the cognitive benefits of the current treatments are limited.The etiology of AD is multifactorial,encompassing Aβand tau accumulation,neuroinflammation,demyelination,vascular dysfunction,and comorbidities,which collectively lead to widespread neurodegeneration in the brain and cognitive impairment.Hence,solely removing Aβfrom the brain may be insufficient to combat neurodegeneration and preserve cognition.To attain effective treatment for AD,it is necessary to(1)conduct extensive research on various mechanisms that cause neurodegeneration,including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level;(2)identify neuroprotective intervention targets against different neurodegeneration mechanisms;and(3)discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients.The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated,multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD.The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD,with the goal of halting or even reversing cognitive decline.展开更多
Dear Editor,Brain-reactive autoantibodies are thought to play an important role in mediating disorders of the central nervous system(CNS).These antibodies direct the processes underlying several diseases,such as multi...Dear Editor,Brain-reactive autoantibodies are thought to play an important role in mediating disorders of the central nervous system(CNS).These antibodies direct the processes underlying several diseases,such as multiple sclerosis(MS),neuromyelitis optica(NMO),and neuropsychiatric systemic lupus erythematosus[1-3].In infectious diseases of the CNS,the pathogen itself is regarded to play a major role in the pathogenesis[4].展开更多
基金supported by the National Natural Science Foundation of China,No.81560215(FW)the Innovative Research Team Program of Science and Technology in Yunnan Province of China,No.2017HC007
文摘Neonatal hypoxic-ischemic encephalopathy is a serious neurological disease,often resulting in long-term neurodevelopmental disorders among surviving children.However,whether these neurodevelopmental issues can be passed to offspring remains unclear.The right common carotid artery of 7-day-old parental-generation rats was subjected to permanent ligation using a vessel electrocoagulator.Neonatal hypoxic-ischemic rat models were established by subjecting the rats to 8%O2–92%N2 for 2 hours.The results showed that 24 hours after hypoxia and ischemia,pathological damage,cerebral atrophy,liquefaction,and impairment were found,and Zea-Longa scores were significantly increased.The parental-generation rats were propagated at 3 months old,and offspring were obtained.No changes in the overall brain structures of these offspring rats were identified by magnetic resonance imaging.However,the escape latency was longer and the number of platform crossings was reduced among these offspring compared with normal rats.These results indicated that the offspring of hypoxic-ischemic encephalopathy model rats displayed cognitive impairments in learning and memory.This study was approved by the Animal Care&Welfare Committee of Kunming Medical University,China in 2018(approval No.kmmu2019072).
基金supported by an Australian Government Research Training Program (RTP) Scholarshipfinancial support of the Cooperative Research Center for Low Carbon Living Ltd. (RP2017 and RP2008) whose activeties are supported by the Cooperative Research Centers program, an Australian Government initiativethe South Australian Health Network for its financial support
文摘Illicit and pharmaceutical drugs are considered to be emerging contaminants of concern,and much research effort has gone into assessing their occurrence in wastewater.However,little information exists on their presence in treated sludge or biosolids.In this study,we examined sludge and biosolids from a large metropolitan wastewater treatment plant(WWTP)in Australia to determine the occurrence of five drugs of abuse,including benzoylecgonine as indicator of cocaine consumption,methamphetamine and 3,4-methylenedioxy methamphetamine(MDMA)as representative illicit stimulants,and codeine and morphine as pharmaceuticals with potential environmental risk.The samples were solid-phase extracted and analyzed by liquid chromatography–tandem mass spectrometry(LC–MS/MS).Benzoylecgonine and MDMA were present in raw sludge but were notably degraded during solids treatment processes,and were not detected in the dewatered sludge(after treatment)or in biosolids.Methamphetamine,codeine,and morphine were detected in all biosolids samples at mean concentrations of 20–50 lg kg^-1.The presence of these three drugs in biosolids shows that these compounds are relatively stable in the solids and in soil,and can persist in biosolids for at least several years.A simple environmental risk assessment based on estimated risk quotients(RQs)for these compounds indicated that the potential environmental risks associated with the land application of biosolids are very low at typical Australian biosolids application rates.
基金supported by the program Innovative Research Team in Science and Technology in Yunnan Province of China(to THW)the National Natural Science Foundation of China,No.81601074Sichuan Provincial Scientific Foundation Grant of China,No.2017SZ0145
文摘A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neonatal hypoxic-ischemic brain damage remain elusive.Seven-day-old rats were used to establish a hypoxic ischemic encephalopathy model.SNPs and expression profiles of mRNAs were analyzed in hypoxic ischemic encephalopathy model rats using RNA sequencing.Genes exhibiting SNPs associated with hypoxic ischemic encephalopathy were identified and studied by gene ontology and pathway analysis to identify their possible involvement in the disease mechanism.We identified 89 up-regulated genes containing SNPs that were mainly located on chromosome 1 and 2.Gene ontology analysis indicated that the up-regulated genes containing SNPs are mainly involved in angiogenesis,wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels.Signaling pathway analysis indicated that the differentially expressed genes play a role in glutamatergic synapses,long-term depression and oxytocin signaling.Moreover,intersection analysis of high throughput screening following PubMed retrieval and RNA sequencing for SNPs showed that CSRNP1,DUSP5 and LRRC25 were most relevant to hypoxic ischemic encephalopathy.Significant up-regulation of genes was confirmed by quantitative real-time polymerase chain reaction analysis of oxygen-glucose-deprived human fetal cortical neurons.Our results indicate that CSRNP1,DUSP5 and LRRC25,containing SNPs,may be involved in the pathogenesis of hypoxic ischemic encephalopathy.These findings indicate a novel direction for further hypoxic ischemic encephalopathy research.This animal study was approved on February 5,2017 by the Animal Care and Use Committee of Kunming Medical University,Yunnan Province,China(approval No.kmmu2019038).Cerebral tissue collection from a human fetus was approved on September 30,2015 by the Ethics Committee of Kunming Medical University,China(approval No.2015-9).
基金supported by a NHMRC senior research fellowship (1042095)supported by the OIS Program of the Victorian Government, Australia+3 种基金the South Australian Cardiovascular Research Development Program funded by the Heart Foundation and the Government of South Australiasupported by a NHMRC Principal Research Fellow- shipfunded by an Australian Postgraduate Award + UniS A Rural and Isolated Top-up Scholarshipfunded through these fellowships and the University of South Australia
文摘AIM To determine the clinical and dietary predictors of common carotid artery intima media thickness(CCA IMT) in a cohort of subjects with type 1 and type 2 diabetes. METHODS Participants with type 1(n = 23) and type 2 diabetes(n = 127) had mean and mean maximum CCA IMT measured using B mode ultrasound. Dietary intake was measured using a food frequency questionnaire. Clinical and dietary predictors of mean and mean maximum CCA IMT were determined using linear regression analysis adjusted for potential confounders. RESULTS The main predictors of mean and mean maximum CCA IMT were age and weight. After multivariate adjustment there were no dietary predictors of CCA IMT. However,in subjects that were not prescribed a lipid lowering medication alcohol consumption was positively associated with CCA IMT after multivariate adjustment. No difference existed in CCA IMT between subjects with type 1 or type 2 diabetes once age was adjusted for. CONCLUSION CCA IMT was predominantly predicted by age and weight in these subjects with diabetes. The finding that CCA IMT was not different between people with type 1 and type 2 diabetes warrants further investigation in a larger cohort.
文摘AIM To discuss type 2 diabetes mellitus(T2DM) medication changes required during the popular 5:2 intermittent energy restriction(IER) diet. METHODS A search was conducted in MEDLINE, EMBASE, AMED, CINAHL and Cochrane library for original research articles investigating the use of very low calorie diets(VLCD) in people with T2 DM. The search terms used included "VLCD" or "very low energy diet" or "very low energy restriction" or "IER" or "intermittent fasting" or "calorie restriction" or "diabetes mellitus type 2" and "type 2 diabetes". Reference lists of selected articles were also screened for relevant publications. Only research articles written in English, which also included an explanation of medication changes were included. A recent pilot trial using the 5:2 IER method, conducted by our research group, will also be summarized.RESULTS A total of 8 studies were found that investigated the use of VLCD in T2 DM and discussed medication management. Overall these studies indicate that the use of a VLCD for people with T2 DM usually require the cessation of medication to prevent hypoglycemia. Therefore, the 5:2 IER method will also require medication changes, but as seen in our pilot trial, may not require total cessation of medication, rather a cessation on the 2 IER days only. CONCLUSION Guidelines outlined here can be used in the initial stages of a 2-d IER diet, but extensive blood glucose monitoring is still required to make the necessary individual reductions to medications in response to weight loss.
文摘Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, however, whether such early gestational and/or lactational exposure can influence the later adult-type Leydig cell phenotype. In this study, Sprague-Dawley rats were exposed to dibutyl phthalate （DBP; from gestational day （GD） 14.5 to postnatal day （PND） 6） or diethylstilbestrol （DES; from GD14o5 to GD16.5） during a short gestationalllactational window, and male offspring subsequently analysed for various postnatal testicular parameters. All offspring remained in good health throughout the study. Maternal xenobiotic treatment appeared to modify specific Leydig cell gene expression in male offspring, particularly during the dynamic phase of mid-puberty, with serum INSL3 concentrations showing that these compounds led to a faster attainment of peak values, and a modest acceleration of the pubertal trajectory. Part of this effect appeared to be due to a treatment-specific impact on Leydig cell proliferation during puberty for both xenobiotics. Taken together, these results support the notion that maternal exposure to certain xenobiotics can also influence the development of the adult-type Leydig cell population, possibly through an effect on the Leydig stem cell population.
基金Supported by Jinling Hospital Medical Research Fund, No. 2005029
文摘AIM： To investigate the relationship between 90-kuD ribosomal $6 kinase （pg0RSK） and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro.METHODS： Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type I were determined by co-immunofluoresence and confocal microscopy.Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell （HSC） line. The expression of collagen type I in HSC-T6 cells was assessed by Western blotting and real-time polymerase chainreaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, thencollagen type I promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated withor without platelet-derived growth factor （PDGF）-BB at a final concentration of 20μg/L and the cell growthwas determined by MTS conversion.RESULTS： In fibrotic liver tissues, p90RSK was over-expressed in activated HSCs and had a significantpositive correlation with collagen type I levels.In HSC-T6 cells transfected with RNAi targeted top90RSK, the expression of collagen type I was down-regulated （61.8% in mRNA, P 〈 0.01, 89.1% inprotein, P 〈 0.01）. However, collagen type ] promoteractivity was not increased with over-expression of p90RSK and not decreased with low expression either,compared with controls in the same cell line （P = 0.076）.Furthermore, p90RSK siRNA exerted the inhibitionof HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation.CONCLUSION： p90RSK is over-expressed in activatedHSCs and involved in regulating the abnormalexpression of collagen type I through initiating theproliferation of HSCs.
文摘This review will examine topical issues in weight loss and weight maintenance in people with and without diabetes. A high protein, low glycemic index diet would appear to be best for 12-mo weight maintenance in people without type 2 diabetes. This dietary pattern is currently beingexplored in a large prevention of diabetes intervention. Intermittent energy restriction is useful but no better than daily energy restriction but there needs to be larger and longer term trials performed. There appears to be no evidence that intermittent fasting or intermittent severe energy restriction has a metabolic benefit beyond the weight loss produced and does not spare lean mass compared with daily energy restriction. Meal replacements are useful and can produce weight loss similar to or better than food restriction alone. Very low calorie diets can produce weight loss of 11-16 kg at 12 mo with persistent weight loss of 1-2 kg at 4-6 years with a very wide variation in long term results. Long term medication or meal replacement support can produce more sustained weight loss. In type 2 diabetes very low carbohydrate diets are strongly recommended by some groups but the long term evidence is very limited and no published trial is longer than 12 mo. Although obesity is strongly genetically based the microbiome may play a small role but human evidence is currently very limited.
基金Supported by (in part) the MS McLeod Post-Doctoral Fellowship obtained from the Women’s and Children’s Hospital Foundation (to Tran CD)
文摘AIM: To examine the effect of increasing dietary zinc (Zn) intake and the lack of metallothionein (MT) expression on activity of small intestinal disaccharidases. METHODS: MT-Ⅰ and Ⅱ knockout (MT-/-) and wild-type (MT+/+) female mice at 3.5 wk of age were randomly fed with a diet containing 2 (2 Zn), 15 (15 Zn) or 50 (50 Zn) mg Zn/kg (n = 8/group/genotype) for 5 wk. Small intestinal segments (duodenum, jejunum and ileum) were collected and either fixed in 10% formalin for histological analysis or snap frozen in liquid nitrogen for sucrase, lactase and maltase activity analyses.RESULTS: Plasma Zn was significantly (P < 0.05) lower (33%) in MT-/- compared with MT+/+ mice fed the 2 Zn diet. Villus height and crypt depth were increased by approximately 15% in MT+/+ mice compared with MT-/- mice. Duodenal disaccharidase activities were significantly higher in MT+/+ compared with MT-/- mice particularly in those fed the 2 Zn diet. For the 50 Zn diet, jejunal sucrase and lactase activities were significantly higher in MT-/- (13 313 ± 2314; 4107 ± 364 μmol glucose/well/min/g tissue, respectively) compared with MT+/+ mice (7054 ± 608; 1818 ± 174). Similarly, ileal lactase activities were higher in MT-/- (1480 ± 192) compared with MT+/+ (629 ± 353) mice particularly those fed the 2 Zn diet. CONCLUSION: Increasing dietary Zn has little effect on disaccharidases activity in MT wild-type mice. The presence of MT may enhance morphological and functional development of the gut.
基金the Heart Foundation and the Government of South Australia,No.CR 12A 6750 to Keogh JBNHMRC Principal Research Fellowship,No.APP1125691 to Clifton PM+2 种基金NHMRC Senior Research Fellowship,No.APP1042095 to Meikle PJan Australian Postgraduate Award,No.138093 to Petersen KSa University of South Australia Postgraduate Award,No.128123 to Lister N
文摘AIM To determine lipid species that change in response to a change in dairy consumption. In addition, to investigate whether dairy associated lipid species are correlated with changes in measures of vascular structure and function.METHODS A 12-mo randomised controlled trial was conducted to determine the effect of increased consumption of fruit, vegetables and dairy, compared to usual diet, on measures of vascular structure and function in adults with type 1 and type 2 diabetes(n = 108). Thispaper comprises post-hoc analyses investigating the relationship between dairy intake, serum lipid species and vascular health. Central and peripheral blood pressure, carotid femoral pulse wave velocity, augmentation index, serum lipid species and dietary intake were measured at baseline and 3-mo. Common carotid artery intima media thickness was measured at baseline and 12-mo.RESULTS Serum lipid species [lysophosphatidylcholine(LPC) 14:0, LPC 15:0, LPC 16:1, phosphatidylcholine(PC) 29:0 PC 30:0, PC 31:0 and cholesterol ester(CE) 14:0] were associated with the change in full fat dairy consumption(rho 0.19-0.25; P < 0.05). The 3-mo change in some lipids was positively associated with the 3-mo change in central systolic [LPC 14:0(rho 0.30; P = 0.007), PC 30:0(rho 0.28; P = 0.010)] and diastolic blood pressure [LPC 14:0(rho 0.32; P = 0.004), LPC 15:0(rho 0.23; P = 0.04), LPC 16:1(rho 0.23; P = 0.035), PC 29:0(rho 0.28; P = 0.01), PC 30:0(rho 0.36; P = 0.001), PC 31:0(rho 0.30; P = 0.007)] and 12-mo change in common carotid artery intimal medial thickness [CE 14:0(rho 0.22; P = 0.02)]. Pulse wave velocity and augmentation index were unrelated to dairy and lipid species.CONCLUSION An increase in dairy associated lipids appears to be associated with an increase in blood pressure and common carotid intimal medial thickness.
基金Project supported by the Australian Research Council(ARC)Linkage Project Grant(No.LP0990847)
文摘Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose ^13 C sodium acetate（^13C-acetate）, which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of ^13CO2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT L100-55 on gelatin capsules and also on DRcaps. Test results demonstrated that DRcaps coated with EUDRAGIT L100-55 possessed enhanced enteric-protective properties, particularly in vivo. These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.
基金This project was supported by an Australian Pacific Science Foundation grant to S.V.C.G., M.I.S. and M.RS., a National Climate Change Adaptation Research Facil- ity grant awarded to S.V.C.G., and an Endeavour fellow- ship award to S.V.C.G. We thank the University of South Pacific for hosting S.V.G.G.＇s research in Fiji.
文摘Morphology-based studies have suggested a very depauperate bee fauna for islands in the South West Pacific, and recent genetic studies since have indicated an even smaller endemic fauna with many bee species in this region resulting from human-aided dispersal. These introduced species have the potential to both disrupt native pollinator suites as well as augment crop pollination, but for most species the timings of introduction are unknown. We examined the distribution and nesting biology of the long-tongued bee Braunsapis puangensis that was first recorded from Fiji in 2007. This bee has now become widespread in Fiji and both its local abundance and geographical range are likely to increase dramatically. The impacts of this invasion are potentially enormous for agriculture and native ecosystems, but they also provide opportunities for understanding how social insect species adapt to new environments. We outline the major issues associated with this recent invasion and argue that a long-term monitoring study is needed.
基金We wish to acknowledge Prostate Cancer UK(RIA15-ST2-022&PhD grant S12-027)for finan cial support and sponsorship,and Yaqeen Sawalha for producing figures for this manuscript.
文摘The functional role of aldehyde dehydrogenases(ALDHs)in prostate cancer remains an area of some controversy.Many studies have used high ALDH functional activity to isolate putative cancer stem cells with tumour-initiating and propagating properties,while evidence is also emerging about the involvement of specific isoforms in migration,invasiveness and metastasis.Identification of specific ALDH isoforms,which contribute to both drug resistance and aggressiveness of the disease remains a challenge within the complex heterogeneity of prostate cancer.The purpose of this perspective is to dissect functional roles for ALDH in the tumour microenvironment and to evaluate the potential of the ALDH gene family as biomarkers and/or targets for therapeutic intervention.
文摘Vaccines are an integral part of veterinary disease prevention. However there are still a significant number of veterinary diseases for which vaccines do not currently exist or where currently available vaccines do not provide adequate immunity. Adenoviruses have transitioned from tools for gene replacement therapy to bona fide vaccine delivery vehicles because of their ability to elicit potent cell-mediated and humoral responses making them ideal for use against viruses and other intracellular pathogens. Adenoviral vector based vaccines are likely to play a significant role in overcoming these problems in the future. However, this vector is under utilized in veterinary vaccine development at this time. This review focuses on adenoviral vector based vaccines developed to date and explores the potential for veterinary vaccine development based upon this platform: advantages and potential disadvantages of this technology are discussed as well as the potential for developing efficacious commercial veterinary adenoviral vector based vaccines.
文摘Accurately measuring inspection time (IT) with computers requires several considerations. They are: 1) Screen redraw period;2) Synchronous and timely image presentation;3) Stimulus duration timing;4) Image scale invariance;5) Stan dardized presentation format (of which image scale invariance is a part). The first consideration dictates a minimum duration available for measuring IT. The second and third are necessary for accurate stimulus duration. The fourth is necessary to provide scale invariant images, that is, images with the same visual angle at a given viewing distance on any computer. And the fifth ensures that participants everywhere respond to the same task. Our computer program em bodies these elements and we make it freely available to any interested party. Data to establish validity and reliability are presented, and normative data on 2518 participants aged 6 to 92 years are available.
文摘Although intensive interventions with low carbohydrate diets compared with higher carbohydrate diets can reduce HbA1c in people with type 2 diabetes, it is not clear if simple advice to make modest reductions in carbohydrate is effective in clinical practice. Forty-three people with type 2 diabetes and poor control (HbA1c > 7.5%) were randomized to receive 2 short education sessions over 6 months with a non-dietitian researcher on how to reduce carbohydrate intake by about 25% or to 2 control sessions in which the Australian Guide to Healthy Eating was provided. Hba1c and fasting glucose and lipids were measured at baseline and 3 months and 6 months. 33 volunteers attended a baseline visit;27 completed 3 months and 24 6 months. HbA1c was reduced by 0.6% - 0.7% in the low carbohydrate diet group compared with the control group (P = 0.1). Fasting glucose was reduced by 2.3 mmol/L compared with the control group at 3 months (P < 0.03) only. Changes in HbA1c at 6 months were related to baseline HbA1c in the intervention group only. Although we have obtained suggestive evidence that a low carbohydrate diet can be successfully implemented in normal practice without professional help, our results are limited by low participant numbers and further studies are required.
文摘BACKGROUND： Spring water therapies have been used since at least 1550 BC. Despite the growing body of evidence supporting these therapies for a range of conditions, including musculoskeletal, dermatological, respiratory and cardiovascular conditions, they do not currently form part of mainstream healthcare in many countries. The protocol established in this paper aims to support systematic reviews that examine the health outcomes associated with human exposure to regional spring waters, using the Australia and New Zealand context as a case study. METHODS/DESIGN： The protocol searches for studies in eight health/medical databases, searches three local health/medical journals, and includes forwards and backwards searching. Standard systematic review methods are used including： specifying pre-deterrnined inclusion criteria and data management plans, appraising the studies for bias, and allocation to a hierarchy of evidence. DISCUSSION： The protocol supports a review and comprehensive synthesis of the current evidence regarding the health effects of natural spring water, and can be adapted for reviews in other regions. From this evidence, recommendations regarding practice and future research can be made on the therapeutic role of spring water.
文摘The degradation of flavonol glycosides extracted from Ginkgo biloba was performed under different conditions and the degraded products were determined by reversed-phase high performance liquid chromatography （RP-HPLC） method.Four stress conditions including acid（0.1 mol/L HCl）,base（0.1 mol/L NaOH）,temperature （70 ℃） and oxidation（0.03% H2O2,volume fraction） were used for the forced degradation studies.The pH stabilities of the flavonol glycosides were determined in phosphate buffers of varying pH values from 4.5 to 7.4.The degradation rate constants and half-life of three Ginkgo flavonol aglycones（quercetin,kaempferol and isorhamnetin） which represent Ginkgo flavonol glycosides were calculated in forced degradation and pH-stability studies of them.The resuits indicate that the three substances were more stable when incubated under acid condition and showed pH-dependent stability.The degradation was observed to follow first-order kinetics in all degradation studies.The stability results could provide important bases on development,preparation and storage of products of Ginkgo biloba extract and should be significantly considered during the further formulation development.
基金National Natural Science Foundation of China,Grant/Award Numbers:92249305,82120108010,81930028,31921003Academy of Medical Sciences(Newton Advanced Fellowship),Grant/Award Number:NAF/R11/1010National Institutes of Health,Grant/Award Number:R01DA056739。
文摘The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a significant pathomechanism in AD,supported by results of recent clinical trials using anti-Aβantibodies.Nonetheless,the cognitive benefits of the current treatments are limited.The etiology of AD is multifactorial,encompassing Aβand tau accumulation,neuroinflammation,demyelination,vascular dysfunction,and comorbidities,which collectively lead to widespread neurodegeneration in the brain and cognitive impairment.Hence,solely removing Aβfrom the brain may be insufficient to combat neurodegeneration and preserve cognition.To attain effective treatment for AD,it is necessary to(1)conduct extensive research on various mechanisms that cause neurodegeneration,including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level;(2)identify neuroprotective intervention targets against different neurodegeneration mechanisms;and(3)discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients.The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated,multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD.The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD,with the goal of halting or even reversing cognitive decline.
基金supported by the National Natural Science Foundation of China(81600936 and 81701046)the Natural Science Foundation of Chongqing Municipality,China(cstc2018jcyJAX0511)。
文摘Dear Editor,Brain-reactive autoantibodies are thought to play an important role in mediating disorders of the central nervous system(CNS).These antibodies direct the processes underlying several diseases,such as multiple sclerosis(MS),neuromyelitis optica(NMO),and neuropsychiatric systemic lupus erythematosus[1-3].In infectious diseases of the CNS,the pathogen itself is regarded to play a major role in the pathogenesis[4].
