High fat diet-induced changes in gut microbiota have been linked to intestinal permeability and metabolic endotoxemia, which is related to metabolic disorders. However, the influence of a high-glucose (HGD) or high-fructose (HFrD) diet on gut microbiota is largely unknown. We performed changes of gut microbiota in HGD- or HFrD-fed C57BL/6J mice by 16S rRNA analysis. Gut microbiota-derived endotoxin-induced metabolic disorders were evaluated by glucose and insulin tolerance test, gut permeability, Western blot and histological analysis. We found that the HGD and HFrD groups had comparatively higher blood glucose and endotoxin levels, fat mass, dyslipidemia, and glucose intolerance without changes in bodyweight. The HGD- and HFrD-fed mice lost gut microbial diversity, characterized by a lower proportion of Bacteroidetes and a markedly increased proportion of Proteobacteria. Moreover, the HGD and HFrD groups had increased gut permeability due to alterations to the tight junction proteins caused by gut inflammation. Hepatic inflammation and lipid accumulation were also markedly increased in the HGD and HFrD groups. High levels of glucose or fructose in the diet regulate the gut microbiota and increase intestinal permeability, which precedes the development of metabolic endotoxemia, inflammation, and lipid accumulation, ultimately leading to hepatic steatosis and normal-weight obesity.

BackgroundElderly people often have more complicated healthcare needs than younger adults due to additional functional decline, physical illness, and psychosocial needs. Unmet healthcare needs increase illness severity, complications, and mortality. Despite this, research on the unmet healthcare needs of elderly people is limited in Korea. This study analysed the effect of functional deterioration related to aging on unmet healthcare needs based on the Korea Health Panel Study.MethodsThis cross-sectional study used data from the 2011–2013 survey of 8666 baseline participants aged 65 years and older. Unmet healthcare needs were calculated using a complex weighted sample design. Group differences in categorical variables were analysed using the Rao-Scott Chi-square test. Using logistic regression analysis, the association between unmet healthcare needs and aging factors was analysed.ResultsThe prevalence of unmet healthcare needs in Korean elderly was 17.4%. Among them, the leading reason was economic hardship (9.2%). Adjusting for sex, age, socioeconomic characteristics, and health-related characteristics, the group with depression syndrome was 1.45 times more likely to have unmet healthcare needs than that without depression syndrome (95% CI = 1.13–1.88). The group with visual impairment was 1.48 times more likely to have unmet healthcare needs than that without it (95% CI = 1.22–1.79). The group with hearing impairment was 1.40 times more likely to have unmet healthcare needs than that without it (95% CI = 1.15–1.72). The group with memory impairment was 1.74 times more likely to have unmet healthcare needs than that without it (95% CI = 1.28–2.36).ConclusionsThe unmet medical needs of the elderly are more diverse than those of younger adults. This is because not only socioeconomic and health-related factors but also aging factors that are important to the health of the elderly are included. All factors were linked organically; therefore, integrated care is needed to improve healthcare among the elderly. To resolve these unmet healthcare needs, it is necessary to reorganize the healthcare system in Korea to include preventive and rehabilitative services that address chronic diseases in an aged society and promote life-long health promotion.

OBJECTIVEThis study investigated the effects of resveratrol, a natural polyphenol with neuroprotective properties, on retinal neuronal cell death mediated by diabetes-induced activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII).RESEARCH DESIGN AND METHODSDiabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin (STZ). Control mice received buffer. All mice were killed 2 months after the injections, and the extent of neuronal cell death, CaMKII, and phospho-CaMKII protein expression levels and CaMKII kinase activity were examined in the retinas. To assess the role of CaMKII in the death of retinal neurons, a small-interfering RNA (siRNA) or specific inhibitor of CaMKII was injected into the right vitreous humor, and vehicle only was injected into the left vitreous humor, 2 days before death. Resveratrol (20 mg/kg) was administered by oral gavage daily for 4 weeks, beginning 1 month after the fifth injection of either STZ or buffer.RESULTSThe death of retinal ganglion cells (RGCs), CaMKII, phospho-CaMKII protein levels, and CaMKII activity were all greatly increased in the retinas of diabetic mice compared with controls, 2 months after induction of diabetes. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)-positive signals co-localized with CaMKII- and phospho-CaMKII immunoreactive RGCs. However, in addition to CaMKII knockdown and inhibition by siRNA or a specific inhibitor, respectively, resveratrol provided complete protection from diabetes-induced retinal cell death.CONCLUSIONSIn the present study, resveratrol prevented diabetes-induced RGC death via CaMKII downregulation, implying that resveratrol may have potential therapeutic applications for prevention of diabetes-induced visual dysfunction.

HHPE used for red ginseng processing contributes to enhanced extraction efficiencies of functional materials such as ginsenosides through cell structure modification.

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OBJECTIVE-Protein kinase C (PKC)-␦, an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein, we examined the role of PKC-␦ in neuronal apoptosis through Akt in the retinas of diabetic rats.RESEARCH DESIGN AND METHODS-We used retinas from 24-and 35-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) diabetic and Long-Evans Tokushima Otsuka (LETO) nondiabetic rats. To assess whether PKC-␦ affects Akt signaling and cell death in OLETF rat retinas, we examined 1) PKC-␦ activity and apoptosis; 2) protein levels of phosphatidylinositol 3-kinase (PI 3-kinase) p85, heat shock protein 90 (HSP90), and protein phosphatase 2A (PP2A); 3) Akt phosphorylation; and 4) Akt binding to HSP90 or PP2A in LETO and OLETF retinas in the presence or absence of rottlerin, a highly specific PKC-␦ inhibitor, or small interfering RNAs (siRNAs) for PKC-␦ and HSP90.RESULTS-In OLETF retinas from 35-week-old rats, ganglion cell death, PKC-␦ and PP2A activity, and Akt-PP2A binding were significantly increased and Akt phosphorylation and Akt-HSP90 binding were decreased compared with retinas from 24-week-old OLETF and LETO rats. Rottlerin and PKC-␦ siRNA abrogated these effects in OLETF retinas from 35-week-old rats. HSP90 siRNA significantly increased ganglion cell death and Akt-PP2A complexes and markedly decreased HSP90-Akt binding and Akt phosphorylation in LETO retinas from 35-week-old rats compared with those from nontreated LETO rats.CONCLUSIONS-PKC-␦ activation contributes to neuro-retinal apoptosis in diabetic rats by inhibiting Akt-mediated signaling pathways. Diabetes 57:2181-2190, 2008 P rotein kinase C (PKC)-␦, a ubiquitously expressed isoform of the novel PKC subfamily, mediates an anti-apoptotic signaling cascade through the phosphatidylinositol 3-kinase (PI 3-kinase)-mediated survival pathway (1,2) and also promotes apoptosis by interfering with Akt signaling (3-5).Akt is a downstream target of PI 3-kinase that plays an integral role in cell survival. Dysregulation of Akt is frequently observed in diseases such as cancers and diabetes (6 -8). PI 3-kinase activates Akt through the phosphorylation of two key regulatory residues, Thr308 and Ser473, on Akt. Phosphorylation of both residues is necessary for full activation of Akt and subsequent regulation of many PI 3-kinase-mediated biological responses (9,10).Protein phosphatase 2A (PP2A), a major cellular serine/ threonine phosphatase, regulates the phosphorylation state of cellular proteins in various pathological conditions (11-13). Recently, it has been reported that PP2A is involved in the regulation of cell proliferation and survival through its ability to dephosphorylate Akt (11-15). Furthermore, heat shock protein 90 (HSP90) counteracts the effect of PP2A in cells through direct binding to Akt, protecting Akt from PP2A-mediated dephosphorylation and thus functioning as a positive regulator of Akt signaling (13,15,16). Of note, numerous reports have suggested that Akt-or HSP-mediated cytoprotection is r...