Histone deacetylase inhibitors: a novel class of therapeutic agents in diabetic nephropathy

Histone deacetylase (HDAC) inhibitors are currently being tested as anticancer agents in clinical trials. Chromatin remodeling, such as through histone acetylation, is a fundamental phenomenon in eukaryotic cell biology, bearing implications to numerous physiological and pathological phenomena. Here, we discuss recent data from our own laboratory and those of others demonstrating antifibrotic and renoprotective effect of HDAC inhibitors in diabetic kidneys, and the possible mechanisms including the role of reactive oxygen species. HDAC inhibitors may prove to be a novel class of multitarget agents in the treatment of diabetic nephropathy.     

Immunomodulation of Fungal β-Glucan in Host Defense Signaling by Dectin-1

During the course of evolution, animals encountered the harmful effects of fungi, which are strong pathogens. Therefore, they have developed powerful mechanisms to protect themselves against these fungal invaders. β-Glucans are glucose polymers of a linear β(1,3)-glucan backbone with β(1,6)-linked side chains. The immunostimulatory and antitumor activities of β-glucans have been reported; however, their mechanisms have only begun to be elucidated. Fungal and particulate β-glucans, despite their large size, can be taken up by the M cells of Peyer''s patches, and interact with macrophages or dendritic cells (DCs) and activate systemic immune responses to overcome the fungal infection. The sampled β-glucans function as pathogen-associated molecular patterns (PAMPs) and are recognized by pattern recognition receptors (PRRs) on innate immune cells. Dectin-1 receptor systems have been incorporated as the PRRs of β-glucans in the innate immune cells of higher animal systems, which function on the front line against fungal infection, and have been exploited in cancer treatments to enhance systemic immune function. Dectin-1 on macrophages and DCs performs dual functions: internalization of β-glucan-containing particles and transmittance of its signals into the nucleus. This review will depict in detail how the physicochemical nature of β-glucan contributes to its immunostimulating effect in hosts and the potential uses of β-glucan by elucidating the dectin-1 signal transduction pathway. The elucidation of β-glucan and its signaling pathway will undoubtedly open a new research area on its potential therapeutic applications, including as immunostimulants for antifungal and anti-cancer regimens.     

艾灸对动脉粥样硬化小鼠炎性反应因子及MMP-9的实验研究

目的:观察艾灸对Apo E~(-/-)小鼠主动脉内肿瘤坏死因子(TNF-α)、白细胞介素-10(IL-10)及基质金属蛋白酶9(MMP-9)的影响,并从抑制炎性反应,稳定动脉粥样硬化斑块等角度探讨艾灸在防治动脉粥样硬化中的机制。方法:将48只采用高脂饮食喂养的载脂蛋白E基因敲除小鼠(Apo E~(-/-)小鼠)作为动脉粥样硬化模型,并随机分为3组:艾灸组,模型组,药物对照组。并将16只同龄相同遗传背景的C57BL/6小鼠作为空白对照组。空白组、模型组小鼠每天常规抓取、固定,并放置假艾灸装置。艾灸组小鼠每天抓取固定,并艾灸膻中穴。药物组小鼠每天采用辛伐他汀0.28 mg/100 g灌胃,所有干预20 min/d,6 d/周,干预14周后牺牲,取材检测。Elisa法测定主动脉内TNF-α、IL-10、MMP-9的含量。油红O染色观察胸主动脉病理改变。结果:1)与模型组相比,艾灸组,药物组小鼠主动脉内TNF-α、MMP-9含量明显降低(P0.05),艾灸组,药物组之间无明显差异;与模型组相比,药物组IL-10水平明显升高有统计学意义(P0.05),艾灸组小鼠主动脉内IL-10呈升高趋势,但无统计学意义。2)胸主动脉病理改变:与空白组相比,模型组胸主动脉可见明显的AS斑块,内膜破坏,中膜增厚,平滑肌细胞破坏变性,管腔变狭窄。相比于模型组,艾灸组及药物组主动脉病变明显减轻。结论:1)艾灸可以有效缓解动脉粥样硬化病变,抑制动脉粥样硬化斑块生长;2)艾灸可以抑制体内炎性反应,并具有稳定斑块的作用     

Effect of resveratrol on the metastasis of 4T1 mouse breast cancer cells in vitro and in vivo

We investigated the effects of resveratrol on metastasis in in vitro and in vivo systems. 4T1 cells were cultured in the presence of various concentrations (0-30 µmol/L) of resveratrol. For experimental metastasis, BALB/c mice were injected intravenously with 4T1 cells in the tail vein, and were orally administered various concentrations (0, 100, or 200 mg/kg Body weight) of resveratrol for 21 days. After resveratrol treatment, cell adhesion, wound migration, invasion, and MMP-9 activity were significantly decreased in a dose-dependent manner in 4T1 cells (P < 0.05). The numbers of pulmonary nodules were significantly decreased in mice fed the resveratrol (P < 0.05). The plasma MMP-9 activity was decreased in response to treatment with resveratrol in mice (P < 0.05). We conclude that resveratrol inhibits cancer metastasis both in vitro and in vivo, and this inhibition is likely due to the decrease in MMP-9 activity caused by resveratrol.     

Computer-Based Identification of Type 2 Diabetic Subjects with and Without Neuropathy Using Dynamic Planter Pressure and Principal Component Analysis

Diabetes is a chronic disease that is characterized by an increased blood glucose level due to insulin resistance. Type 2 diabetes is common in middle aged and old people. In this work, we present a technique to analyze dynamic foot pressures images and classify them into normal, diabetes type 2 with and without neuropathy classes. Plantar pressure images were obtained using the F-Scan (Tekscan, USA) in-shoe measurement system. We used Principal Component Analysis (PCA) and extracted the eigenvalues from different regions of the foot image. The features extracted from region 1 of the foot pressure image, which were found to be clinically significant, were fed into the Fuzzy classifier (Sugeno model) for automatic classification. Our results show that the proposed method is able to identify the unknown class with an accuracy of 93.7%, sensitivity of 100%, and specificity of 83.3%. Moreover, in this work, we have proposed an integrated index using the eigenvalues to differentiate the normal subjects from diabetes with and without neuropathy subjects using just one number. This index will help the clinicians in easy and objective daily screening, and it can also be used as an adjunct tool to cross check their diagnosis.     

Premature or Just Small? Training Guatemalan Birth Attendants to Weigh and Assess Gestational Age of Newborns: An Analysis of Outcomes

We describe Guatemalan birth attendants’ identification of vulnerable newborns, their evaluation of gestational age and anthropometry, and the validity of the Capurro and New Ballard newborn gestational age assessment methods. We interviewed 49 birth attendants and trained 10 of these women to assess 63 newborns. The Capurro and Ballard methods were correlated (Spearman rho = .75, p < .001) and showed agreement (Bland-Altman plot, difference and bias, ?0.33 ± 1.3 weeks). Prematurity was estimated at 27% (Ballard) and 24% (Capurro); low birth weight (LBW) was 30%. Capurro provided a simplified, equivalent estimate of gestational age compared with New Ballard that could be used by birth attendants.     

Brain Stem Hypoplasia Associated with Cri-du-Chat Syndrome

Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.     

Endemic Norovirus Infections in Children,Ho Chi Minh City,Vietnam, 2009–2010

We performed a case–control investigation to identify risk factors for norovirus infections among children in Vietnam. Of samples from 1,419 children who had diarrhea and 609 who were asymptomatic, 20.6% and 2.8%, respectively, were norovirus positive. Risk factors included residential crowding and symptomatic contacts, indicating person-to-person transmission of norovirus.     

Both HCV and HBV are Major Causes of Liver Cancer in Southeast Asians

The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians.