Multifaceted effects of aluminium in neurodegenerative diseases: A review

Aluminium (Al) is the most common metal and widely distributed in our environment. Al was first isolated as an element in 1827, and its use began only after 1886. Al is widely used for industrial applications and consumer products. Apart from these it is also used in cooking utensils and in pharmacological agents, including antacids and antiperspirants from which the element usually enters into the human body. Evidence for the neurotoxicity of Al is described in various studies, but still the exact mechanism of Al toxicity is not known. However, the evidence suggests that the Al can potentiate oxidative stress and inflammatory events and finally leads to cell death.Al is considered as a well-established neurotoxin and have a link between the exposure and development of neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s disease (AD), dementia, Gulf war syndrome and Parkinsonism. Here, we review the detailed possible pathogenesis of Al neurotoxicity. This review summarizes Al induced events likewise oxidative stress, cell mediated toxicity, apoptosis, inflammatory events in the brain, glutamate toxicity, effects on calcium homeostasis, gene expression and Al induced Neurofibrillary tangle (NFT) formation. Apart from these we also discussed animal models that are commonly used for Al induced neurotoxicity and neurodegeneration studies. These models help to find out a better way to treat and prevent the progression in Al induced neurodegenerative diseases.     

免疫组化检测膀胱癌中netrin-1的表达

目的:比较不同病理分期膀胱癌组织标本中netrin-1表达量的差异,分析其表达量与膀胱癌临床分期的关系。方法:选取膀胱癌组织标本100例,免疫组化方法检测netrin-1表达量。结果:netrin-1在膀胱癌组织中随病理分期的升高,表达量增加(P<0.05)。结论:netrin-1表达量与膀胱癌临床病理分期显著相关,对推测膀胱癌的术前分期以及对临床选择治疗方案和估计预后具有重要意义。     

Association between the NBS1 Glu185Gln polymorphism and breast cancer risk: a meta-analysis

Nijmegen breakage syndrome 1 (NBS1), a vital DNA repair protein in the homologous recombination repair pathway and a signal modifier in the intra-S phase checkpoint, plays a critical role in cellular response to DNA damages and the maintenance of genomic stability. The NBS1 Glu185Gln (NBS1 E185Q, NBS1 8360G>C, rs1805794) polymorphism has been indicated to be involved in the development of cancer, but results of previous individual studies on the association between NBS1 Glu185Gln polymorphism and breast cancer risk remain controversial and inconclusive. Our meta-analysis investigated this association for the first time by pooling the odds ratios with corresponding 95 % confidence intervals (95 % CIs) of all individual publications available to date. Overall, 14 separate studies with 6,642 cases and 7,138 controls were finally included into the present meta-analysis after a comprehensive literature search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to October 21, 2012. Overall analysis and subgroup analyses by ethnicity and source of controls were performed. Meta-analysis of total studies showed that the NBS1 Glu185Gln variant carriers were not susceptible to breast cancer (OR_{Gln vs. Glu}?=?1.05, 95 % CI 0.80–1.39, P _OR?=?0.719; OR _{Gln/Gln vs. Glu/Glu}?=?0.82, 95 % CI 0.62–1.08, P _OR?=?0.154; OR _{Glu/Gln vs. Glu/Glu}?=?1.00, 95 % CI 0.90–1.13, P _OR?=?0.939; OR_{Gln/Gln + Glu/Gln vs. Glu/Glu}?=?0.96, 95 % CI 0.83–1.11, P _OR?=?0.551; OR_{Gln/Gln vs. Glu/Glu + Glu/Gln}?=?0.84, 95 % CI 0.67–1.05, P _OR?=?0.134). Similar results were observed in heterogeneity-adjusted meta-analysis of all studies. Furthermore, subgroup analyses by ethnicity and source of controls did not identify any appreciable relationship of the NBS1 Glu185Gln polymorphism with breast cancer susceptibility in any populations. Sensitivity analysis by sequentially omitting individual studies confirmed the stability and reliability of our results. Our meta-analysis of currently available data shows no association between the NBS1 Glu185Gln polymorphism and breast cancer risk.     

Impact of demographic,environmental, and lifestyle factors on vitamin D sufficiency in 9084 Japanese adults

BackgroundLittle is known about correlates of vitamin D status in Asian populations. In this study, we established the prevalence of vitamin D sufficiency in the Murakami region (latitude N38°13′) in Niigata, Japan, and examined demographic, environmental, and lifestyle factors that might be associated with vitamin D sufficiency, with the aim of clarifying the relative contributions of previously described determinants of vitamin D status as well as identifying new determinants in this Japanese population.MethodsThis study involved a cross-sectional analysis of baseline data obtained from a cohort study conducted in 2011–2013. Participants were 9084 individuals aged between 40 and 74 years who provided blood samples for the determination of plasma 25-hydroxyvitamin D [25(OH)D] concentrations. Lifestyle information was obtained from 8498 participants, with some missing values regarding different lifestyle factors. Multiple logistic regression analysis was used to obtain odds ratios for vitamin D sufficiency, which was defined as a plasma 25(OH)D concentration ≥ 75 nmol/L.ResultsThe prevalence of vitamin D sufficiency (i.e., plasma 25(OH)D concentration ≥ 75 nmol/L) was 9.1%, and significant associations were observed with male gender (P < 0.0001; OR = 2.37, 95% CI: 1.84–3.05), older age (P for trend < 0.0001), lower BMI (P for trend < 0.0001), higher METs score (P for trend = 0.0138), higher vitamin D intake (P for trend = 0.0467), summer season (P for trend < 0.0001), longer duration outdoors (P for trend = 0.0026), no sunscreen use (P = 0.0135; OR = 1.40, 95% CI: 1.07–1.82), higher salmon consumption (P for trend < 0.0001), higher alcohol consumption (P for trend < 0.0001), and lower coffee consumption (P for trend = 0.0025). Unlike other populations previously reported, vitamin D sufficiency was associated with older age.ConclusionsThe prevalence of vitamin D sufficiency (i.e., 25[OH]D ≥ 75 nmol/L) was low (9.1%) in this Japanese population. A number of demographic, environmental, and lifestyle factors are associated with vitamin D sufficiency, and thus lifestyle modification may present an opportunity to achieve vitamin D sufficiency.     

A meta-analysis of the prognosis in patients with breast cancer with ipsilateral supraclavicular lymph node metastasis versus patients with stage IIIb/c or IV breast cancer

ObjectiveTo systematically evaluate the prognosis in patients with breast cancer with ipsilateral supraclavicular lymph node metastasis (SLNM) versus patients with stage IIIb/c or IV breast cancer, so as to provide evidence for clinical practice and research.MethodsComputer retrieval from PubMed, Cochrane Libratory, CNKI (China National Knowledge Infrastructure), CBM and Wanfang Database with the assistance of other retrieval tools. All the studies evaluating the prognosis in patients with breast cancer with ipsilateral supraclavicular lymph node metastasis versus patients with stage IIIb/c or IV breast cancer were collected. Quality assessment was performed for the included data based on the quality assessment criteria appropriate for this study. Meta-analysis was performed using RevMan 5.3 software.ResultsA total of four references (1277 patients) were included. Assessment of influences on prognosis: As compared to the stage IIIb/c group, the 5-year survival rate was slightly lower in the SLNM group (relative risk (RR) 0.79; 95% confidence interval (CI) 0.59–1.06; Z = 1.55, P = 0.12), but there was no statistical significance; in contrast, the 5-year survival rate was significantly increased in the SLNM group as compared to the stage IV group (RR = 2.70; 95%CI: 1.36–5.37; Z = 2.84, P = 0.005). As compared to the stage IIIb/c group, the 5-year disease-free survival rate was lower in the SLNM group (RR = 0.65; 95%CI: 0.40–1.05; Z = 1.75, P = 0.08); however, there was no statistical significance.ConclusionsIn patients with advanced breast cancer receiving combined therapy, the prognosis in patients with breast cancer with ipsilateral SLNM was significantly better than in those with stage IV breast cancer, and slightly worse than those with stage IIIb/c breast cancer. However, with the scarcity and poor quality of these observational studies, the long-term prognosis remains to be further verified in large-sample, high-quality studies.     

Effects of upper extremity aerobic exercise training on oxygen consumption,exercise capacity,dyspnea and quality of life in patients with pulmonary arterial hypertension

BackgroundPulmonary and extrapulmonary impairments are prevalent in pulmonary arterial hypertension (PAH) which is a rare, chronic and progressive disease.ObjectivesTo investigate the effects of upper extremity aerobic exercise training on exercise capacity, oxygen consumption, dyspnea and quality of life in patients with PAH.MethodsIn a prospective, randomized controlled, double-blinded study, eleven patients in training group applied upper extremity aerobic exercise training (50–80% of maximal heart rate), 15–45 min/day, 3 days a week for 6 weeks and 11 patients in control group alternating active upper extremity exercises for the same period. Exercise capacity evaluated using six minute walk test (6MWT), oxygen consumption simultaneously measured during 6MWT using a portable instrument, dyspnea modified Borg scale and Modified Medical Research Council dyspnea scale and quality of life Short Form 36 Health Survey, before and after the exercise training.ResultsBaseline characteristics of groups were similar (p>0.05). Dyspnea (p<0.001) and peak oxygen consumption (p = 0.031) were significantly improved in training group compared the controls. Dyspnea, exercise capacity, peak oxygen consumption, minute ventilation, tidal volume, end tidal carbon-dioxide pressure, and vitality, social functioning and role-physical were significantly improved within training group (p<0.05). Oxygen consumption at anaerobic threshold were significantly decreased within control group (p<0.05).ConclusionsUpper extremity aerobic exercise training improves oxygen consumption, and decreases dyspnea perception. It is a safe and effective intervention in patients with PAH. (ClinicalTrials.gov registration: NCT02371733).     

DPD、MTHFR和TS表达水平与氟尿嘧啶类药物治疗消化道肿瘤疗效及预后关系的研究进展

消化道恶性肿瘤包括结直肠癌、胃癌和食管癌等。尽管使用了各种治疗方式，癌症患者仍然有复发和转移。绝大多数患者确诊时即为中晚期，因而化疗在癌症患者中发挥重要作用。作为5-FU抗癌活性中的三个关键酶，二氢嘧啶脱氢酶（DPD）、5,10-亚甲基四氢叶酸还原酶（MTHFR）、胸苷酸合成酶（TS）与消化道肿瘤的疗效、对化疗药物的敏感性及患者的预后有密切关系。