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Cover Illustration
2015, Vol.6  No.4
 BrdU-positive cells expressed nestin and vimentin in adult kidney in rat.  BrdU-positive cells (red) in the tubule (top panel) and the glomerulus (bottom panel) expressed nestin (green) 3 days after ischemia. [Detail] ...

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  • Table of Content
      01 August 2015, Volume 6 Issue 4 Previous Issue    Next Issue
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    Original Article
    Increasing Proliferation of Intrinsic Tubular Cells after Renal Ischemia-reperfusion Injury in Adult Rat
    Feng Jian, Hu Weiming, Feng Chunyue, Mao XiaoOu, Jin Kunlin, Ye Youxin
    Aging and disease. 2015, 6 (4): 228-235.   DOI: 10.14336/AD.2014.0917
    Abstract   HTML   PDF (1255KB) ( 1234 )

    The kidney is capable of regeneration following injury. However, whether renal stem/progenitor cells contribute to the repair process after injury, as well as the origin of the cells that repair and replace damaged renal tubule cells remains debated. Therefore, better understanding of the repair process will be critical to developing new strategies for the treatment of acute renal failure. Using an ischemia-reperfusion injury mode and an immunocytochemistry method, we counted the number of BrdU-positive cells in damged regions at different durations of reperfusion. We found that BrdU, a cell proliferative marker, was mainly incorporated in the tubular cells of both medulla and cortex 1 day after reperfusion. The number of BrdU-positive cells reached a peak at 3 days and lasted for two months after injury. BrdU-positive cells were barely found in the renal glomerulus and the parietal layer of Bowman’s capsule after injury, and only a few were found in the intersititium. PAX2, an embryonic renal marker, was also increased in renal tubule cells. Confocal images show that BrdU-positive cells co-expressed PAX2, but not the activated form of caspase-3, a cell death marker. Our data suggest that renal stem-like cells or dedifferentiation of surviving renal tubular cells in both the medulla and cortex may predominantly contribute to the repair process after renal ischemia-reperfusion injury in rat.

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    Clinical Characteristics for the Relationship between Type-2 Diabetes Mellitus and Cognitive Impairment: A Cross-Sectional Study
    Zhou Yi, Fang Rong, Liu Li-Hua, Chen Sheng-Di, Tang Hui-Dong
    Aging and disease. 2015, 6 (4): 236-244.   DOI: 10.14336/AD.2014.1004
    Abstract   HTML   PDF (950KB) ( 1344 )

    We explored the potential differences in cognitive status, lipid and glucose metabolism, ApoEε4 alleles and imaging between diabetic and non-diabetic subjects. 83 subjects with normal cognitive function and 114 mild cognitive impaired patients were divided into four groups by history of diabetes. General demographics was collected from all participants followed by MRI scan, biochemical examinations and a series of neuropsychological tests. Student’s t test, multiple regressions and one-way ANOVA were applied to investigate the differences between groups. Comparing diabetic patients with non-diabetic subjects in the mild cognitive impaired group, we found several decreased items in recall of three words in MMSE (p=0.020), AVLT and SCWT (p<0.050). The multiple linear regression revealed that two-hour glucose level (B= -0.255,p<0.001) and fasting C-peptide (B= -0.466,p=0.001) had negative effects on the score of MMSE. In addition, diabetic patients treated with insulin and other diabetes medication performed better in part of the AVLT (p<0.050) compared to patients with insulin treatment or oral antidiabetic medication only. Patients with metformin medication had a better memory outcome compared to patients with sulphonylurea medication in the AVLT long delay free recall (p =0.010). These findings show that patients of mild cognitive impairment with diabetes mellitus have a worse outcome in attention, information processing speed and memory compared to non-diabetic patients. Higher two-hour glucose level and C-peptide level may be risk factors for severe cognitive impairment in type-2 diabetes mellitus patients. The results of this study also suggest that medication may have effects on cognitive function.

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    Herbal Formula Danggui-Shaoyao-San Promotes Neurogenesis and Angiogenesis in Rat Following Middle Cerebral Artery Occlusion
    Ren Changhong, Wang Brian, Li Ning, Jin Kunlin, Ji Xunming
    Aging and disease. 2015, 6 (4): 245-253.   DOI: 10.14336/AD.2014.1126
    Abstract   HTML   PDF (1378KB) ( 1270 )

    Current studies demonstrated that traditional Chinese herbal formula Danggui-Shaoyao-San (DSS) is not only used for the treatment of menstrual disorder, but has also found its use in neurological diseases. However, the neuroprotective role of DSS on ischemia-induced brain injury is still unclear. The aim of the present study is to explore the effect of DSS in ischemic brain injury. Total 30 adult female Sprague-Dawley rats underwent 90 min transient middle cerebral artery occlusion (MCAO). DSS (600 mg/kg) was administered through the intragastric route at the time of reperfusion and then performed every day thereafter until sacrifice. Results showed that DSS treatment significantly improved neurobehavioral outcomes (N=10 per group, P<0.05). Immunohistochemical staining showed that microvessel density in the perifocal region of DSS-treated rats was significantly increased compared to the saline-treated group (N=4 per group, P<0.01). Similarly, the numbers of BrdU+/DCX+ cells in the subventricular zone were increased in DSS-treated rats compared to the saline-treated group (P<0.05). Furthermore, we demonstrated that DSS treatment activated vascular endothelial growth factor (N=4 per group,P<0.05) and promoted eNOS phosphorylation (N=4 per group,P<0.05). Thus, we concluded that DSS promoted focal angiogenesis and neurogenesis, and attenuated ischemia-induced brain injury in rats after MCAO, suggesting that DSS is a potential drug for ischemic stroke therapy.

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    Review Article
    Activity-Based Restorative Therapies after Spinal Cord Injury: Inter-institutional conceptions and perceptions
    R. Dolbow David, S. Gorgey Ashraf, C. Recio Albert, A. Stiens Steven, C. Curry Amanda, L. Sadowsky Cristina, R. Gater David, Martin Rebecca, W. McDonald John
    Aging and disease. 2015, 6 (4): 254-261.   DOI: 10.14336/AD.2014.1105
    Abstract   HTML   PDF (545KB) ( 1109 )

    This manuscript is a review of the theoretical and clinical concepts provided during an inter-institutional training program on Activity-Based Restorative Therapies (ABRT) and the perceptions of those in attendance. ABRT is a relatively recent high volume and intensity approach toward the restoration of neurological deficits and decreasing the risk of secondary conditions associated with paralysis after spinal cord injury (SCI). ABRT is guided by the principle of neuroplasticity and the belief that even those with chronic SCI can benefit from repeated activation of the spinal cord pathways located both above and below the level of injury. ABRT can be defined as repetitive-task specific training using weight-bearing and external facilitation of neuromuscular activation. The five key components of ABRT are weight-bearing activities, functional electrical stimulation, task-specific practice, massed practice and locomotor training which includes body weight supported treadmill walking and water treadmill training. The various components of ABRT have been shown to improve functional mobility, and reverse negative body composition changes after SCI leading to the reduction of cardiovascular and other metabolic disease risk factors. The consensus of those who received the ABRT training was that ABRT has much potential for enhancement of recovery of those with SCI. Although various institutions have their own strengths and challenges, each institution was able to initiate a modified ABRT program.

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    Low HbA1c and Increased Mortality Risk-is Frailty a Confounding Factor?
    H Abdelhafiz Ahmed, J Sinclair Alan
    Aging and disease. 2015, 6 (4): 262-270.   DOI: 10.14336/AD.2014.1022
    Abstract   HTML   PDF (600KB) ( 1465 )

    Diabetes mellitus is increasingly becoming an older person disease due to the increased survival and aging of the population. Previous studies which showed benefits of tight glycemic control and a linear relationship between HbA1c and mortality have largely included younger patients newly diagnosed with diabetes and with less comorbidities. Recent studies, which included older population with diabetes, have shown a U-shaped relationship of increased mortality associated with low HbA1c. The mechanism of such relationship is unclear. There was no direct causal link between low HbA1c and mortality. It appears that malnutrition, inflammation and functional decline are characteristics shared by the populations that showed increased mortality and low HbA1c. In these studies functional status, disability or frailty was not routinely measured. Therefore, although adjustment for comorbidities was made there may be a residual confounding by unmeasured factors such as frailty. Thus, frailty or decline in functional reserve may be the main confounding factor explaining the relationship between increased mortality risk and low HbA1c.

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    Does Upper Extremity Training Influence Body Composition after Spinal Cord Injury?
    A. Fisher Justin, A. McNelis Meredith, S. Gorgey Ashraf, R. Dolbow David, L. Goetz Lance
    Aging and disease. 2015, 6 (4): 271-281.   DOI: 10.14336/AD.2014.0912
    Abstract   HTML   PDF (840KB) ( 1362 )

    Spinal cord injury (SCI) leads to serious body composition adaptations characterized by increasing whole body fat mass and decreased soft tissue lean mass (LM). These adaptations in body composition may lead to several cardio-metabolic disorders that reduce the quality of life, increase patients’ and caregivers’ burden and eventually leads to mortality. Exercise, an appropriate dietary regimen, and an active lifestyle may alleviate several of the negative effects on body composition after a SCI. Today however, there is no established consensus on the recommended dose, frequency or type of exercise to ameliorate several of the body composition sequelae after an acute SCI. Resistance training has been previously recommended as an effective strategy to restore soft tissue LM and decrease fat mass (FM). The strategy can be simply implemented as a routine home-based training program using free weights or resistance bands after a SCI. Additionally, upper extremity (UE) circuit resistance training has been previously used to improve cardiovascular and metabolic parameters after a SCI; however compared to the vast knowledge regarding the able-bodied (AB) population, the effects of UE circuit resistance training on body composition after a SCI is not well established. In summary, the available evidence does not support the rationale that UE circuit resistance training can lead to positive adaptations in body composition after a SCI. Further studies are suggested to examine the effects of UE circuit resistance training on body composition.

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    Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment
    Chakrabarti Sasanka, Kumar Khemka Vineet, Banerjee Anindita, Chatterjee Gargi, Ganguly Anirban, Biswas Atanu
    Aging and disease. 2015, 6 (4): 282-299.   DOI: 10.14336/AD.2014.002
    Abstract   HTML   PDF (1071KB) ( 1424 )

    Alzheimer's disease (AD), the major cause of dementia among the elderly world-wide, manifests in familial and sporadic forms, and the latter variety accounts for the majority of the patients affected by this disease. The etiopathogenesis of sporadic AD is complex and uncertain. The autopsy studies of AD brain have provided limited understanding of the antemortem pathogenesis of the disease. Experimental AD research with transgenic animal or various cell based models has so far failed to explain the complex and varied spectrum of AD dementia. The review, therefore, emphasizes the importance of AD related risk factors, especially those with metabolic implications, identified from various epidemiological studies, in providing clues to the pathogenesis of this complex disorder. Several metabolic risk factors of AD like hypercholesterolemia, hyperhomocysteinemia and type 2 diabetes have been studied extensively both in epidemiology and experimental research, while much less is known about the role of adipokines, pro-inflammatory cytokines and vitamin D in this context. Moreover, the results from many of these studies have shown a degree of variability which has hindered our understanding of the role of AD related risk factors in the disease progression. The review also encompasses the recent recommendations regarding clinical and neuropathological diagnosis of AD and brings out the inherent uncertainty and ambiguity in this area which may have a distinct impact on the outcome of various population-based studies on AD-related risk factors.

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Kunlin Jin, M.D., Ph.D., Professor
Ashok K. Shetty, Ph.D., Professor
David A. Greenberg, M.D., Ph.D., Professor
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