Huntington's disease (HD) is an inherited neurodegenerative disorder typified by involuntary body movements, and psychiatric and cognitive abnormalities. Many HD patients also exhibit metabolic ...changes including progressive weight loss and appetite dysfunction. Here we have investigated metabolic function in pre-manifest and manifest HD subjects to establish an HD subject metabolic hormonal plasma signature. Individuals at risk for HD who have had predictive genetic testing showing the cytosine-adenine-guanine (CAG) expansion causative of HD, but who do not yet present signs and symptoms sufficient for the diagnosis of manifest HD are said to be "pre-manifest." Pre-manifest and manifest HD patients, as well as both familial and non-familial controls, were evaluated for multiple peripheral metabolism signals including circulating levels of hormones, growth factors, lipids, and cytokines. Both pre-manifest and manifest HD subjects exhibited significantly reduced levels of circulating growth factors, including growth hormone and prolactin. HD-related changes in the levels of metabolic hormones such as ghrelin, glucagon, and amylin were also observed. Total cholesterol, HDL-C, and LDL-C were significantly decreased in HD subjects. C-reactive protein was significantly elevated in pre-manifest HD subjects. The observation of metabolic alterations, even in subjects considered to be in the pre-manifest stage of HD, suggests that in addition, and prior, to overt neuronal damage, HD affects metabolic hormone secretion and energy regulation, which may shed light on pathogenesis, and provide opportunities for biomarker development.
The aging process affects every tissue in the body and represents one of the most complicated and highly integrated inevitable physiological entities. The maintenance of good health during the aging ...process likely relies upon the coherent regulation of hormonal and neuronal communication between the central nervous system and the periphery. Evidence has demonstrated that the optimal regulation of energy usage in both these systems facilitates healthy aging. However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity. Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration. In this study, we examined alterations in protein expression in the hypothalami of young, middle-aged, and old rats. Using novel combinatorial bioinformatics analyses, we were able to gain a better understanding of the proteomic and phenotypic changes that occur during the aging process and have potentially identified the G protein-coupled receptor/cytoskeletal-associated protein GIT2 as a vital integrator and modulator of the normal aging process.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anorexia nervosa (AN) is a debilitating eating disorder characterized by severely restricted eating and significant body weight loss. In addition, many individuals also report engaging in excessive ...exercise. Previous research using the activity-based anorexia (ABA) model has implicated the hypothalamic proopiomelanocortin (POMC) system. Using the ABA model,
mRNA has been shown to be transiently elevated in both male and female rodents undergoing ABA. In addition, the POMC peptide β-endorphin appears to contribute to food anticipatory activity (FAA), a characteristic of ABA, as both deletion and antagonism of the µ opioid receptor (MOR) that β-endorphin targets, results in decreased FAA. The role of β-endorphin in reduced food intake in ABA is unknown and POMC neurons release multiple transmitters in addition to β-endorphin. In the current study, we set out to determine whether targeted inhibition of POMC neurons themselves rather than their peptide products would lessen the severity of ABA. Inhibition of POMC neurons during ABA via chemogenetic Designer Receptors Exclusively Activated by Designer Drugs (DREADD) technology resulted in reduced FAA in both male and female mice with no significant changes in body weight or food intake. The selective reduction in FAA persisted even in the face of concurrent chemogenetic inhibition of additional cell types in the hypothalamic arcuate nucleus. The results suggest that POMC neurons could be contributing preferentially to excessive exercise habits in patients with AN. Furthermore, the results also suggest that metabolic control during ABA appears to take place via a POMC neuron-independent mechanism.
Huntington's disease (HD) is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, ...body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg) rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP), heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4), glycogen synthase1 (Gys1) and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1). In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Text mining is rapidly becoming an essential technique for the annotation and analysis of large biological data sets. Biomedical literature currently increases at a rate of several thousand papers ...per week, making automated information retrieval methods the only feasible method of managing this expanding corpus. With the increasing prevalence of open-access journals and constant growth of publicly-available repositories of biomedical literature, literature mining has become much more effective with respect to the extraction of biomedically-relevant data. In recent years, text mining of popular databases such as MEDLINE has evolved from basic term-searches to more sophisticated natural language processing techniques, indexing and retrieval methods, structural analysis and integration of literature with associated metadata. In this review, we will focus on Latent Semantic Indexing (LSI), a computational linguistics technique increasingly used for a variety of biological purposes. It is noted for its ability to consistently outperform benchmark Boolean text searches and co-occurrence models at information retrieval and its power to extract indirect relationships within a data set. LSI has been used successfully to formulate new hypotheses, generate novel connections from existing data, and validate empirical data.
Abstract Aims This review investigated the population impact of major modifiable type 2 diabetes (T2D) risk factors, with special focus on native Asian Indians, to estimate population attributable ...risks (PARs) and compare them with estimates from Chinese and Japanese populations. Methods Information was obtained on risk factors in 21,041 Asian Indian, 17,774 Chinese and 17,986 Japanese populations from multiple, large, cross-sectional studies (the DECODA project) of T2D. Crude and adjusted PARs were estimated for the major T2D risk factors. Results Age had the highest crude and adjusted PARs among Asian Indians and Chinese in contrast to waist–hip ratio among Japanese. After adjusting for age, the PAR for body mass index (BMI) in Asian Indians (41.4% 95% CI: 37.2%; 45.4%) was second only to triglycerides (46.4% 95% CI: 39.5%; 52.8%) compared with 35.8% 95% CI: 29.9%; 41.4% in Japanese and 38.4% 95% CI: 33.5%; 43.2% in Chinese people. The PAR for BMI adjusted for age, LDL and triglycerides (39.7% 95% CI: 31.6%; 47.2%) was higher than for any other factor in Asian Indians, and was much higher than in the Chinese (16.8% 95% CI: 3.0%; 30.9%) and Japanese (30.4% 95% CI: 17.5%; 42.2%) populations. Conclusion This review provides estimates of the association between major risk factors and prevalences of T2D among Asian populations by examining their PARs from large population-based samples. From a public-health point of view, the importance of BMI in Asian Indians is especially highlighted in comparison to the other Asian populations. Given these results and other recent findings on the causality link between BMI and T2D, it can be postulated that obesity may be involved in the aetiology of T2D through interaction with ethnic-specific genetic factors, although ethnicity itself is not a direct risk factor for T2D as people of all ethnic backgrounds develop diabetes.
Background and purpose: Recent studies have shown that kidney dysfunction is associated with cerebral small vessel disease (SVD). Although creatinine‐based estimating equations have been used as the ...standard measure for the evaluation of kidney function, the accuracy of these is limited in the elderly because of muscle mass decrease with aging. Cystatin C is a more useful measurement than creatinine‐based estimating equations for evaluating kidney function, however, the relationship amongst cystatin C, cognitive dysfunction, and cerebral SVD has not been fully examined in community‐based elderly.
Methods: We performed a cross‐sectional study using MRI to determine the relationship amongst cystatin C, cognitive function, and cerebral SVD in a total of 604 community‐based Japanese elderly.
Results: In this study, subjects with higher cystatin C levels tended to have more lacunas and higher grades of white matter lesions. Although a decline of the Mini‐Mental State Examination (MMSE) scores was associated with SVD‐related lesions, the relationship between the tertiles of cystatin C and mean MMSE scores was not statistically significant. In the logistic regression analysis, the association between cystatin C and SVD‐related lesions was statistically significant, even after adjustment for conventional risk factors and high‐sensitivity C‐reactive protein. Furthermore, subjects with higher cystatin C levels accompanied with albuminuria had a greater risk for the presence of subclinical cerebral SVD than those with lower cystatin C levels without albuminuria.
Conclusions: The present study suggests that there is a close relationship between cystatin C and subclinical cerebral SVD, independently of conventional risk factors, in community‐based elderly.
Echocardiography plays a pivotal role as an imaging modality in modern cardiology practice. Information derived from echocardiography is definitely helpful for patient care. The Japanese Society of ...Echocardiography has promoted echocardiography in routine clinical and research use. One of the missions of the Society is to provide information that is useful for high-quality examinations. To ensure this, we believe that equipment in good condition and a comfortable environment are important for both patient and examiner. Here, the Guideline Preparation Committee of the Japanese Society of Echocardiography has established brief guidance for the routine use of echocardiography equipment.
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