Frailty has been previously studied in Western countries and the urban Korean population; however, the burden of frailty and geriatric conditions in the aging populations of rural Korean communities had not yet been determined. Thus, we established a population-based prospective study of adults aged ≥ 65 years residing in rural communities of Korea between October 2014 and December 2014. All participants underwent comprehensive geriatric assessment that encompassed the assessment of cognitive and physical function, depression, nutrition, and body composition using bioimpedance analysis. We determined the prevalence of frailty based on the Cardiovascular Health Study (CHS) and Korean version of FRAIL (K-FRAIL) criteria, as well as geriatric conditions. We recruited 382 adults (98% of eligible adults; mean age: 74 years; 56% women). Generally, sociodemographic characteristics were similar to those of the general rural Korean population. Common geriatric conditions included instrumental activity of daily living disability (39%), malnutrition risk (38%), cognitive dysfunction (33%), multimorbidity (32%), and sarcopenia (28%), while dismobility (8%), incontinence (8%), and polypharmacy (3%) were less common conditions. While more individuals were classified as frail according to the K-FRAIL criteria (27%) than the CHS criteria (17%), the CHS criteria were more strongly associated with prevalent geriatric conditions. Older Koreans living in rural communities have a significant burden of frailty and geriatric conditions that increase the risk of functional decline, poor quality of life, and mortality. The current study provides a basis to guide public health professionals and policy-makers in prioritizing certain areas of care and designing effective public health interventions to promote healthy aging of this vulnerable population.
Cisplatin (cis-diamminedichloroplatinum II) is a platinum coordinated complex that is widely used as an antineoplastic agent for the treatment of many solid tumors, including cancers of the ovary, testis, lung, bladder, head and neck, cervix and endometrium.1) Despite its excellent anticancer activity, the clinical use of cisplatin is often limited by its undesirable side effects, such as severe nephrotoxicity and hepatotoxicity. 2,3) Although the precise mechanism for this cisplatin-induced toxicity is not well understood, cisplatin is taken up preferentially and accumulates in the human liver and kidney cells, 4) resulting in the enhanced production of reactive oxygen species (ROS) and the decrease in the antioxidant enzymes.5,6) Therefore, antioxidants have been administered before a cisplatin treatment to protect against nephrotoxicity. 7)Licorice is an esteemed crude drug in both the Orient and Occident that is originated from the dried roots of several Glycyrrhiza species, including Glycyrrhiza uralensis FISCHER, G. glabra LINNE and G. inflata BATALIN. 8,9) In Chinese traditional medicine, licorice remains one of the most commonly prescribed herbs and has been used in the treatment of various ailments ranging from tuberculosis to peptic ulcers.10) Licorice has also been employed as a flavoring and sweetening agent, as well as a demulcent and expectorant in Western countries.11) The chemical constituents of licorice include glycyrrhizin and its aglycone, glycyrrhetinic acid, which are originally isolated from aqueous extracts and are used in the treatment of hyperlipemia, atherosclerosis, viral diseases, allergic inflammation and hepatotoxicity.12,13) The acetone or ethanol extract of licorice has species-specific flavonoids, such as liquiritin, isoliquiritin and their corresponding aglycones, glabridin, glabrol, glabrene, hispaglabridin A and hispaglabridin B.14,15) These flavonoids exhibit antioxidative, 16) superoxide scavenging 16) and anticarcinogenic activities.17) However, in vivo antitumor activity of a licorice extract and its protective activity on cisplatin-induced toxicity have not yet been studied.In the present study to assess the antitumor activity of a licorice extract and whether it has the potential to serve as a beneficial supplement during cisplatin chemotherapy, we examined the inhibitory effect of the licorice extract alone and in combination with cisplatin on the tumor growth, and its protective effect against cisplatin-induced nephrotoxicity and hepatotoxicity in mice xenografted with mouse colon carcinoma cells. MATERIALS AND METHODSChemical Cisplatin, phenylmethylsulfonyl fluoride (PMSF), sodium nitrite, 1,1,3,3-tetramethoxypropane, reduced glutathione (GSH), 5,5Ј-dithiobis(2-nitrobenzoic acid) (DTNB), glutathione reductase, reduced nicotinamide adenine dinucleotide phosphate (NADPH), superoxide dismutase (SOD), xanthine oxidase, a-naphthylamine, sulfanilic acid, xanthine, catalase and 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (purpald ® ) were purchased from SigmaAldrich Chem...
In the tumor microenvironment, CD11b+Gr1+ bone marrow-derived cells are a predominant source of pro-tumorigenic factors such as matrix metalloproteinases (MMPs), but how distal tumors regulate these cells in the bone marrow is unclear. Here we addressed the hypothesis that the parathyroid hormone-related protein (PTHrP) potentiates CD11b+Gr1+ cells in the bone marrow of prostate tumor hosts. In two xenograft models of prostate cancer, levels of tumor-derived PTHrP correlated with CD11b+Gr1+ cell recruitment and microvessel density in the tumor tissue, with evidence for mediation of CD11b+Gr1+ cell-derived MMP-9 but not tumor-derived VEGF-A. CD11b+Gr1+ cells isolated from mice with PTHrP-overexpressing tumors exhibited relatively increased pro-angiogenic potential, suggesting that prostate tumor-derived PTHrP potentiates this activity of CD11b+Gr1+ cells. Administration of neutralizing PTHrP monoclonal antibody reduced CD11b+Gr1+ cells and MMP9 in the tumors. Mechanistic investigations in vivo revealed that PTHrP elevated Y418 phosphorylation levels in Src family kinases in CD11b+Gr1+ cells via osteoblast-derived IL-6 and VEGF-A, thereby upregulating MMP-9. Taken together, our results showed that prostate cancer-derived PTHrP acts in the bone marrow to potentiate CD11b+Gr1+ cells, which are recruited to tumor tissue where they contribute to tumor angiogenesis and growth.
Abstract. A growing amount of attention has been focused on the investigation of the effects of chemopreventive agents on the inhibition of cancer cell growth and toxicity in combination with chemotherapeutics. The objective of this study was to determine whether isoliquiritigenin (ISL) has the potential to serve as a beneficial supplement during cisplatin chemotherapy. We found that the administration of ISL alone significantly reduced the size of the solid tumors in CT-26 cell-inoculated BALB / c mice, without any detectable induction of nephrotoxicity, hepatotoxicity, and oxidative stress, and ISL reduced the viability and DNA synthesis of CT-26 murine colon cancer cells in a dose-dependent manner. ISL did not affect the therapeutic efficacy of cisplatin. Furthermore, ISL suppressed cisplatin-induced kidney damage characterized by increases in serum creatinine and blood urea nitrogen, as well as cisplatin-induced liver damage characterized by increases in serum alanine aminotransferase and aspartate aminotransferase. The repeated oral administration of ISL prior to cisplatin treatment exerted a preventive effect on cisplatin-mediated increases in serum nitric oxide and tissue lipid peroxidation levels, and it recovered depleted GSH levels in the tissues. Therefore, supplementation with ISL may be an effective approach to counteracting the side effects of cisplatin therapy in cancer patients.
PurposeWe aimed to describe the age- and sex-specific distributions of gait speed and to evaluate associations with longitudinal outcomes in Korean rural community-dwelling older adults.Patients and methodsA total of 1,348 people (mean age: 76 years, 55% women) in the population-based, prospective cohort of Aging Study of Pyeongchang Rural Area (ASPRA) between October 2014 and June 2017. All participants underwent a comprehensive geriatric assessment, including 4-m usual gait speed, and were followed annually.ResultsAmong the 1,348 participants, women had a slower gait speed than men (mean 0.709 m/s vs 0.850 m/s, P < 0.001). Gait speed was inversely associated with age, frailty index; slow gait speed as classified by sex-specific quartile was associated with the prevalence of common geriatric syndromes. During the mean follow-up period of 21.5 months (SD 7.88), future survival without mortality or institutionalization was affected by sex-specific gait-speed quartile (log rank test P < 0.001): the 1st quartile of sex-specific gait speed was associated with increased risk of death or institutionalization.ConclusionGait speed was related to age, sex, frailty status, and geriatric health outcomes in Korean rural community-dwelling older adults. Since this gait-speed distribution in an older Korean population differs from previous data on other populations, we should consider a gait-speed cutoff value based on sex-specific quartiles to prevent misclassification in sarcopenia and frailty diagnosis.
PurposeThe primary aim of this study was to evaluate the effectiveness of a 6-month multicomponent intervention on physical function in socioeconomically vulnerable older adults in rural communities. As secondary aims, we evaluated the effectiveness of the intervention on frailty and other geriatric syndromes, sustained benefit at 12 months, and baseline characteristics associated with poor response.Patients and methodsThis designed-delay study was conducted in 187 adults (mean age: 77 years; 75% women) who were living alone or on a low income in three rural regions of Korea. A 24-week multicomponent program that consisted of group exercise, nutritional supplementation, depression management, deprescribing medications, and home hazard reduction was implemented with a planned 6-month interval from August 2015 through January 2017. The primary outcome was physical function, measured using the Short Physical Performance Battery (SPPB) score (range: 0–12; minimum clinically important difference ≥1) at 6 months. Secondary outcomes included frailty phenotype, sarcopenia, Mini Nutritional Assessment-Short Form score (range: 0–14), Center for Epidemiologic Studies-Depression Scale score (range: 0–60), and falls.ResultsAt 6 months, the SPPB score increased by 3.18 points (95% CI: 2.89, 3.48) from baseline. The program improved frailty (odds ratio: 0.06; 95% CI: 0.02, 0.16), sarcopenia (odds ratio: 0.32; 95% CI: 0.15, 0.68), Mini Nutritional Assessment-Short Form score by 1.67 points (95% CI: 1.28, 2.06), and Center for Epidemiologic Studies-Depression Scale score by −3.83 points (95% CI: −5.26, −2.39), except for fall (rate ratio: 0.99; 95% CI: 0.69, 1.43). These beneficial effects were sustained at 12 months. Body mass index ≥27 kg/m2 and instrumental activities of daily living disability at baseline were associated with poor improvement in the SPPB score.ConclusionThis 24-week multicomponent program had sustained beneficial effects up to 1 year on physical function, frailty, sarcopenia, depressive symptoms, and nutritional status in socioeconomically vulnerable older adults in rural communities. (ClinicalTrials.gov, NCT 02554994)
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