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With the increasing prevalence of age-related chronic diseases burdening healthcare systems, there is a pressing need for innovative management strategies. Our study focuses on the gut microbiota, essential for metabolic, nutritional, and immune functions, which undergoes significant changes with aging. These changes can impair intestinal function, leading to altered microbial diversity and composition that potentially influence health outcomes and disease progression. Using advanced metagenomic sequencing, we explore the potential of personalized probiotic supplements in 297 older adults by analyzing their gut microbiota. We identified distinctive Lactobacillus and Bifidobacterium signatures in the gut microbiota of older adults, revealing probiotic patterns associated with various population characteristics, microbial compositions, cognitive functions, and neuroimaging results. These insights suggest that tailored probiotic supplements, designed to match individual probiotic profile, could offer an innovative method for addressing age-related diseases and functional declines. Our findings enhance the existing evidence base for probiotic use among older adults, highlighting the opportunity to create more targeted and effective probiotic strategies. However, additional research is required to validate our results and further assess the impact of precision probiotics on aging populations. Future studies should employ longitudinal designs and larger cohorts to conclusively demonstrate the benefits of tailored probiotic treatments.
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Envelhecimento , Suplementos Nutricionais , Microbioma Gastrointestinal , Probióticos , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Humanos , Idoso , Feminino , Masculino , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Lactobacillus/genética , Metagenômica/métodos , BifidobacteriumRESUMO
Mild cognitive impairment (MCI) is recognized as the prodromal phase of dementia, a condition that can be either maintained or reversed through timely medical interventions to prevent cognitive decline. Considerable studies using functional magnetic resonance imaging (fMRI) have indicated that altered activity in the medial prefrontal cortex (mPFC) serves as an indicator of various cognitive stages of aging. However, the impacts of intrinsic functional connectivity in the mPFC as a mediator on cognitive performance in individuals with and without MCI have not been fully understood. In this study, we recruited 42 MCI patients and 57 healthy controls, assessing their cognitive abilities and functional brain connectivity patterns through neuropsychological evaluations and resting-state fMRI, respectively. The MCI patients exhibited poorer performance on multiple neuropsychological tests compared to the healthy controls. At the neural level, functional connectivity between the mPFC and the anterior cingulate cortex (ACC) was significantly weaker in the MCI group and correlated with multiple neuropsychological test scores. The result of the mediation analysis further demonstrated that functional connectivity between the mPFC and ACC notably mediated the relationship between the MCI and semantic fluency performance. These findings suggest that altered mPFC-ACC connectivity may have a plausible causal influence on cognitive decline and provide implications for early identifications of neurodegenerative diseases and precise monitoring of disease progression.
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Disfunção Cognitiva , Giro do Cíngulo , Imageamento por Ressonância Magnética , Córtex Pré-Frontal , Humanos , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Giro do Cíngulo/diagnóstico por imagem , Masculino , Feminino , Idoso , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos de Casos e ControlesRESUMO
Diabetes nephropathy (DN) is one of the most common causes of end stage renal disease (ESRD) globally. Medication options to stop or slow the progression of chronic renal disease (CKD) are limited, and patients with DN remain at a high risk of developing renal failure. Inonotus obliquus extracts (IOEs) of Chaga mushroom have been shown to have anti-glycemic, anti-hyperlipidemia, antioxidant, and anti-inflammatory effects against diabetes. In this study, we examined the potential renal protective role of an ethyl acetate layer after water-ethyl acetate separation from Inonotus obliquus ethanol crude extract (EtCE-EA) from Chaga mushrooms in diabetic nephropathy mice after preparation with 1/3 NT + STZ. Our data showed that treatment with EtCE-EA can effectively regulate blood glucose, albumin-creatinine ratio, serum creatinine, and blood urea nitrogen (BUN) levels, and it can improve the renal damage in 1/3 NT + STZ-induced CRF mice with an increase in concentration (100, 300, and 500 mg/kg). In the immunohistochemical staining test, EtCE-EA can effectively reduce the expression of TGF-ß and α-SMA after induction according to the increase in the concentration (100 mg/kg, 300 mg/kg), thereby slowing down the degree of kidney damage. Our findings demonstrate that EtCE-EA could provide renal protection in diabetes nephropathy, possibly due to the decreased expression of transforming growth factor-ß1 and α-smooth muscle actin.
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Diabetes Mellitus , Nefropatias Diabéticas , Camundongos , Animais , Nefropatias Diabéticas/metabolismo , Estreptozocina/farmacologia , Rim/metabolismo , Nefrectomia/efeitos adversos , Diabetes Mellitus/metabolismoRESUMO
OBJECTIVES: To investigate the effectiveness of family caregiver-administered home-based manual massages in managing dementia symptoms and reducing caregiver stress. METHODS: Thirty-eight pairs of participants-patients with dementia and their family caregivers-were randomly allocated to the experimental or the control group. The caregivers underwent 3-h-long massage training. Subsequently, the patients received a 30-min-long, home-based massage from their caregivers thrice a week for 8 consecutive weeks. The Cornell Scale for Depression in Dementia (CSDD), Cohen-Mansfield Agitation Inventory (CMAI), and Perceived Stress Scale (PSS) were assessed before and after the interventions. RESULTS: After intervention, the experimental group exhibited significant improvements in CSDD and CMAI scores compared with the scores of the control group (all p < .001). Furthermore, the experimental group obtained more favorable PSS scores than did the control group (p = .013). CONCLUSIONS: Family caregiver-administered home-based massage therapy is recommended for managing dementia symptoms and reducing caregiver stress.
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Cuidadores , Demência , Humanos , Cuidadores/educação , Demência/terapia , Escalas de Graduação Psiquiátrica , MassagemRESUMO
BACKGROUND: This study investigated the determinants and use of Taiwan's long-term care (LTC) Plan Version 2.0 (LTC 2.0) services by persons with dementia (PWDs) and their caregivers. METHODS: In total, 1268 PWD-caregiver dyads were enrolled for analysis from a national dementia registry. Andersen's Behavioral Model of Health Services Use was used to investigate the association of LTC service use with several factors, namely the demographic data of PWDs and their caregivers, migrant caregiver employment, monthly household income, caregiver burden as determined by the Zarit Burden Interview (ZBI), Mini-Mental State Examination score, Clinical Dementia Rating scores, neuropsychiatric inventory scores for the behavioral and psychological symptoms of dementia, and PWDs' activities of daily living (ADLs). RESULTS: Among the studied family caregivers, 81.4% did not use LTC resources. A multivariable logistic analysis revealed that aberrant motor behaviors (odd ratio [OR] = 1.31, 95% confidence interval [CI] = 1.10-1.56, p = 0.003), dysfunction in ADLs (OR = 1.06, 95% CI = 1.02-1.10, p = 0.002), higher ZBI scores (OR = 1.02, 95% CI = 1.01-1.03, p = 0.004), not residing with family members (OR = 1.88, 95% CI = 1.32-2.66, p < 0.001), and not employing a migrant caregiver (OR = 4.41, 95% CI = 2.59-7.51, p < 0.001) were the factors most significantly associated with LTC service use. CONCLUSION: Factors such as whether PWDs live alone, specific neuropsychiatric symptoms, and impaired function should be considered in future policy amendments to provide required activities and care resources for PWDs and their caregivers.
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Purpose Alzheimer disease (AD) is an irreversible neurodegenerative disease that causes progressive cognitive decline. Co-existing thymoma should be considered when rapid deterioration of cognition was noted in AD patients and removal of thymoma may improve cognition in AD. Case report We report a 72-year-old woman with initial complaints of memory impairment for 2 years. After detailed history taking, neuropsychological tests, brain magnetic resonance imaging, and positive amyloid positron emission tomography, she was diagnosed as having dementia of the Alzheimer type. At the time of diagnosis, her dementia condition was mild (clinical dementia rating [CDR] is equal to 1, CDR sum of boxes [CDR-sb] = 4.5, Mini-Mental State Examination (MMSE) is equal to 21 divided by 30). She needed moderate assistance in performing daily life activities. One year after AD diagnosis, her condition deteriorated drastically, and she experienced frequent falls and severe weakness apart from cognitive symptoms. Concurrent myasthenia gravis (MG) with thymoma was found later, and thymectomy was performed. Her symptoms related to MG alleviated after the operation. Notably, her cognitive symptoms also improved 4 months after the operation, and her dementia reversed to mild cognitive impairment. Conclusion Although the role of neuroinflammation in AD has been widely discussed, it remains elusive. Removal of the co-existing thymoma not only alleviated the patient's MG symptoms but also improved her cognitive performance. We supposed that this effect may have been a direct result of the decrease in acetylcholine receptor antibody or reduction in the degree of neuroinflammation. Keywords Alzheimer disease, thymoma, neuroinflammation, central cholinergic effects, acetylcholine receptor antibody.
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OBJECTIVES: To explore the effects of a 10-week manual massage intervention given by caregivers of patients with dementia on the behavioral and psychological symptoms of dementia (BPSD) and caregiver burden. METHODS: Twelve pairs of participants-patients with dementia and their family caregivers-were recruited. Before the intervention, caregivers received a four-hour full body manual massage training course. Thereafter, the caregivers gave a 30-min massage to the patients once a week for a 10-week period. The Cornell Scale for Depression in Dementia, Cohen-Mansfield Agitation Inventory, and Zarit Burden Scale were administered pre- and post-intervention. RESULTS: Total scores on all questionnaires significantly decreased after the intervention (p < .05). Moreover, two subscale scores of the Cornell Scale for Depression in Dementia-behavioral disturbance and physical signs-reduced significantly (p < .05). CONCLUSIONS: This study provides preliminary evidence on the benefits of manual massage given by caregivers for the management of BPSD and caregiver burden.
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Cuidadores , Demência , Ansiedade , Cuidadores/psicologia , Demência/psicologia , Humanos , Massagem , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Dementia in the oldest-old is projected to increase exponentially as is the burden of their caregivers who may experience unique challenges and suffering. Thus, we aim to investigate which factors are associated with older caregivers' burden in caring demented outpatients in a multicenter cohort. METHODS: Patients and their caregivers, both aged â§65 years, in the National Dementia Registry Study in Taiwan (T-NDRS) were included in this study. Caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). The correlations between the ZBI scores and characteristics of caregivers and patients, including severity of dementia, physical comorbidities, instrumental activities of daily living (IADL), neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory (NPI), and family monthly income, were analyzed. RESULTS: We recruited 328 aged informal caregiver-patient dyads. The mean age of caregivers was 73.7 ± 7.0 years, with female predominance (66.8%), and the mean age of patients was 78.8 ± 6.9 years, with male predominance (61.0%). Multivariable linear regression showed that IADLs (ß = 0.83, p < 0.001) and NPI subscores of apathy (ß = 3.83, p < 0.001)and irritability (ß = 4.25, p < 0.001) were positively associated with ZBI scores. The highest family monthly income (ß = - 10.92, p = 0.001) and caregiver age (ß = - 0.41, p = 0.001) were negatively correlated with ZBI scores. CONCLUSIONS: Older caregivers of older demented patients experience a higher care burden when patients had greater impaired functional autonomy and the presence of NPI symptoms of apathy and irritability. Our findings provide the direction to identify risky older caregivers, and we should pay more attention to and provide support for these exhausted caregivers.
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Atividades Cotidianas , Cuidadores , Idoso , Idoso de 80 Anos ou mais , Sobrecarga do Cuidador , Estudos de Coortes , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Taiwan/epidemiologiaRESUMO
BACKGROUND: Taiwan is a rapidly aging society. The elderly with mild cognitive impairment (MCI) have increased risk of dementia, and this is a population-based report using standard neuropsychological tests and expert consensus diagnosis to assess the MCI prevalence and its associated factors in Taiwan. METHOD: The Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT) is a community-based, prospective cohort study. Independently-living individuals aged â§60 years in a rural area (n = 122) and in an urban area (n = 348) of New Taipei City, Taiwan, completed detailed neuropsychological tests at the cohort baseline. Diagnosis of MCI was ascertained through expert consensus based on 2011 NIA-AA criteria. RESULTS: Of 470 participants recruited between 2017 and 2019 (mean age 71.2 ± 5.4 years), the prevalence of MCI was higher in the rural area than in the urban area (25.1% vs. 10.8%, p < 0.001) after standardized for age, gender, and level of education. Having lower education and having depression symptoms were consistently associated with increased risk of MCI in both urban and rural areas (p < 0.05). Being male and diabetes were additionally associated with MCI prevalence in urban areas. CONCLUSION: In this community-based prospective cohort study in Taiwan, the prevalence of MCI in the rural community was much higher than that in the urban community. Different strategies may be needed to targeted different types of communities.
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Disfunção Cognitiva , Vida Independente , Idoso , Disfunção Cognitiva/epidemiologia , Humanos , Masculino , Testes Neuropsicológicos , Prevalência , Estudos Prospectivos , Fatores de Risco , População Rural , Taiwan/epidemiologiaRESUMO
BACKGROUND/PURPOSE: Screening of dementia can help to initiate proper management of the disorder. The use of the Ascertain Dementia 8-item Questionnaire (AD8) in screening has been promoted in Taiwan recently. The purpose of this study was to compare the psychometric properties and appropriateness of informant-reported and self-rated AD8 in cognitive impairment screening in Taiwan. METHODS: The AD8 were administered to 153 participants and their informants recruited from two neurology out-patient clinics. The discriminative abilities for early cognitive impairment [Clinical Dementia Rating scale (CDR) 0.5 and 1] of informant-based and self-rating AD8 were determined and compared with their areas under the receiver operating curve. κ coefficients representing the agreement between self-rated and informant-reported AD8 scores were also calculated. RESULTS: Participants and their informants were aged 76.9 years and 56.0 years on average, respectively. Only informant-reported AD8 was significantly associated with CDR level (Spearman ρ=0.469, p<0.001) and Cognitive Abilities Screening Instrument score (Spearman ρ=-0.458, p<0.001). The item-by-item agreements between self-rated and informant-reported AD8 were poor (κ coefficients: -0.030 to 0.206). The area under the receiver-operator characteristic curve was 0.59 for self-rated AD8 scores, and 0.77 for informant-reported AD8 scores, indicating that the discriminating ability of AD8 scores between CDR 0 and CDR 0.5 or greater is better when reported by informant than when rated by self. CONCLUSION: Informant-rated AD8 gave more accurate screening results than self-reported AD8 in an out-patient clinic setting.
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Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Programas de Rastreamento/métodos , Testes Neuropsicológicos , Autorrelato , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Curva ROC , Sensibilidade e Especificidade , TaiwanRESUMO
BACKGROUND: The relationship between early life experience and the occurrence of neuropsychiatry symptoms (NPSs) in patients with Alzheimer disease (AD) is unclear. METHODS: From 2012 to 2014, we prospectively recruited 250 patients with probable AD from the memory clinic of Taipei Veterans General Hospital. All patients underwent standard assessments, including brain magnetic resonance imaging or computed tomography, neuropsychological tests, neuropsychiatry inventory (NPI-Q) and related blood tests. A linear regression analysis was performed to investigate the relationship between NPSs and age, gender, disease severity, depression, language background (with or without Japanese education). RESULTS: Among the 250 participants, 113 (45.2%) were women. Their average age was 82.6 years. Of all the participants, 93 (37.2%) had received formal Japanese education, whereas 157 (62.8%) did not receive Japanese education. The participants with Japanese education were slightly younger (83.1 ± 3.6 vs. 81.4 ± 3.4, P = 0.006), with a higher proportion of them were women (30.5% vs. 69.8%, P < 0.001) and fewer years of total education (10.8 ± 4.5 vs. 7.7 ± 3.2, P < 0.001), compared to the participants without Japanese education. NPI-Q scores significantly differed between the two groups (15.8 vs. 24.1, P = 0.024). Both disease severity and language background predicted NPI-Q scores. CONCLUSIONS: Language background in early life may be related to NPSs in patients with AD, and this effect is more significant in patients with a lower education level than in those with a higher education level. More NPSs may be the result of negative effects on dominant language or early life experiences.
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Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Idioma , Comportamento Verbal , Idoso de 80 Anos ou mais , Escolaridade , Feminino , Avaliação Geriátrica , Humanos , Japão , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , Fatores SocioeconômicosRESUMO
BACKGROUND: Increasing evidence shows that bilingualism or multilingualism may have beneficial effects on preventing dementia. We performed a cross-sectional, community-based study in Taiwan. Some elders (older than 70 years) in Taiwan can speak Japanese because of the formal Japanese education they received before World War II, when Taiwan was under Japanese rule. After the war, Mandarin Chinese was adopted as the official language of Taiwan. We assessed whether constantly using three languages had an effect on dementia prevalence and cognitive function. METHODS: We defined multilingualism as the ability to fluently speak Taiwanese (T), Japanese (J), and Mandarin Chinese (C) in daily life. We evaluated the Mini-Mental State Examination and AD8 questionnaire results of 514 community-dwelling people older than 70 years in Taishan, Taiwan. RESULTS: Seventy-three of the subjects (14.2%) were multilingual (T, J, C) and 441 (85.8%) were bilingual (T, C). No difference was noted in dementia prevalence between multilingual (6.8%) and bilingual (7.4%) populations, but multilinguals were older than bilinguals (mean age: 79.9 vs 77.3 years). Multilinguals had higher Mini-Mental State Examination scores than bilinguals (mean: 24.6 vs. 22.7). However, after the subjects were stratified into low and high education level groups, the Mini-Mental State Examination difference was found to be significant in only the low education level group. CONCLUSIONS: Dementia prevalence did not significantly differ between the multilingual (T, J, C) and bilingual (T, C) groups. However, given that the average age of the multilingual group was approximately 2 years older than that of the bilingual group, there may have been minor effects in the multilingual group.
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Povo Asiático , Cognição/fisiologia , Idioma , Multilinguismo , Estudos Transversais , Demência/epidemiologia , Demência/psicologia , Escolaridade , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Prevalência , Taiwan/epidemiologiaRESUMO
BACKGROUND: Previous studies in western countries have shown that about 30%-50% of patients with frontotemporal lobar degeneration (FTLD) have a positive family history, whereas the few epidemiological studies on FTLD done in Asia reported much lower frequencies. It is not clear the reason why the frequencies of FTLD with positive family history were lower in Asia. Furthermore, these findings were not from studies focused on family history. Therefore, it is necessary to conduct further studies on the family history of FTLD in Asia. This international multi-center research aims to investigate the family histories in patients with FTLD and related neurodegenerative diseases such as progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and motor neuron diseases in a larger Asian cohort. METHODS: Participants were collected from five countries: India, Indonesia, Japan, Taiwan, and Philippines. All patients were diagnosed with behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive non-fluent aphasia (PA), frontotemporal dementia with motor neuron disease (FTD/MND), PSP, and corticobasal degeneration (CBD) according to international consensus criteria. Family histories of FTLD and related neurodegenerative diseases were investigated in each patient. RESULTS: Ninety-one patients were included in this study. Forty-two patients were diagnosed to have bvFTD, two patients had FTD/MND, 22 had SD, 15 had PA, one had PA/CBS, five had CBS and four patients had PSP. Family history of any FTLD spectrum disorder was reported in 9.5% in bvFTD patients but in none of the SD or PA. CONCLUSION: In contrast to patients of the western countries, few Asian FTLD patients have positive family histories of dementia.
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Degeneração Lobar Frontotemporal , Linhagem , Ásia/epidemiologia , Sintomas Comportamentais/diagnóstico , Família , Saúde da Família/estatística & dados numéricos , Feminino , Degeneração Lobar Frontotemporal/diagnóstico , Degeneração Lobar Frontotemporal/epidemiologia , Degeneração Lobar Frontotemporal/etiologia , Degeneração Lobar Frontotemporal/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricosRESUMO
OBJECTIVES: This study aimed to explore the relationship between multidimensional factors, such as environment, health status, behavior, social support, and the well-being of middle-aged and older adults. METHODS: This study utilized data from 2 waves of the nationally representative Taiwan Longitudinal Study on Aging Survey Report (TLSA) conducted in 2015 and 2019. The TLSA assesses socioeconomic status, physical and health status, the 5-item World Health Organization Well-Being Index (WHO-5 index), and social support. Data regarding the degree of digital development were obtained from the 2020 Township Digital Development Report. We applied a generalized estimating equation (GEE) to analyze the influencing factors. RESULTS: This study included 4796 participants. Residing in areas with a higher degree of digital development, having a higher socioeconomic status, and experiencing better physical and mental health were significantly associated with well-being. Furthermore, emotional and attentive support mediated the association between physical and mental status and well-being. CONCLUSION: People's awareness of searching for and receiving social support and medical resources is important for enhancing their well-being. It is also crucial to pay attention to the living environment and maintain one's health status to promote well-being.
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Nível de Saúde , Saúde Mental , Apoio Social , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Longitudinais , Taiwan/epidemiologia , Classe Social , Idoso de 80 Anos ou mais , Estudos de Coortes , Fatores SocioeconômicosRESUMO
BACKGROUND: Cognitive impairment (CI) is one of the major complications in chronic kidney disease patients, especially those with end-stage renal disease (ESRD). Limited biomarkers have been found that can significantly predict ESRD-associated cognitive decline. OBJECTIVE: This cohort study aimed to investigate de novo biomarkers for diagnosis of the ESRD-associated CI. METHODS: In this cohort study, qualified samples were divided into control (with an estimated glomerular filtration rate (eGFR) of≥60âmL/min and a Mini-Mental State Examination (MMSE) score ofâ>â27), ESRD without CI (eGFRâ<â15 and MMSEâ>â27), and ESRD with CI (eGFRâ<â15 and MMSEâ<â27) groups. Levels of plasma amyloid-ß (Aß)1 - 42, serum indoxyl sulfate, and hematologic and biochemical parameters were measured. RESULTS: Compared to the control group, levels of blood urea nitrogen, creatinine, and indoxyl sulfate were elevated in ESRD patients both without and with CI. Interestingly, ESRD patients with CI had the lowest levels of serum albumin. In contrast, levels of plasma Aß1 - 42 were significantly higher in the ESRD with CI group than in the control and ESRD without CI groups. In addition, the ratio of plasma Aß1 - 42 over serum albumin was significantly higher in the ESRD with CI group than in the control or ESRD without CI groups. Importantly, the area under the receiver operating characteristic curve (AUROC) for CI in the total population by the ratio of Aß1 - 42 over albumin was 0.785 and significant (pâ<â0.05). CONCLUSIONS: This cohort study has shown that the ratio of plasma Aß1 - 42 over serum albumin can be a de novo biomarker for the diagnosis and prognosis of ESRD-associated cognitive decline.
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Disfunção Cognitiva , Falência Renal Crônica , Humanos , Estudos de Coortes , Albumina Sérica , Indicã , Falência Renal Crônica/complicações , Taxa de Filtração Glomerular , Biomarcadores , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Peptídeos beta-AmiloidesRESUMO
Osteoporosis is characterized by low bone mass, bone microarchitecture disruption, and collagen loss, leading to increased fracture risk. In the current study, collagen peptides were extracted from milkfish scales (MS) to develop potential therapeutic candidates for osteoporosis. MS was used to synthesize a crude extract of fish scales (FS), collagen liquid (COL), and hydroxyapatite powder (HA). COL samples were further categorized according to the peptide size of total COL (0.1 mg/mL), COL < 1 kDa (0.1 mg/mL), COL: 1-10 kDa (0.1 mg/mL), and COL > 10 kDa (0.1 mg/mL) to determine it. Semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and immunofluorescence labeling were used to assess the expression levels of specific mRNA and proteins in vitro. For in vivo studies, mice ovariectomy (OVX)-induced postmenopausal osteoporosis were developed, while the sham surgery (Sham) group was treated as a control. Collagen peptides (CP) from MS inhibited osteoclast differentiation in RAW264.7 cells following an insult with nuclear factor kappa-B ligand (RANKL). CP also enhanced osteoblast proliferation in MG-63 cells, possibly through downregulating NFATc1 and TRAP mRNA expression and upregulating ALP and OPG mRNA levels. Furthermore, COL1 kDa also inhibited bone density loss in osteoporotic mice. Taken together, CP may reduce RANKL-induced osteoclast activity while promoting osteoblast synthesis, and therefore may act as a potential therapeutic agent for the prevention and control of osteoporosis.
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Glaucoma is considered a neurodegenerative disease characterized by progressive visual field defects that may lead to blindness. Although controlling intraocular pressure (IOP) is the mainstay of glaucoma treatment, some glaucoma patients have unmet needs due to unclear pathogenic mechanisms. Recently, there has been growing evidence that neuroinflammation is a potential target for the development of novel antiglaucoma agents. In this study, we investigated the protective effects and cellular mechanisms of H7E, a novel small molecule inhibits HDAC8, using in vitro and in vivo glaucoma-like models. Importantly, H7E mitigated extracellular MMP-9 activity and MCP-1 levels in glutamate- or S100B-stimulated reactive Müller glia. In addition, H7E inhibited the upregulation of inflammation- and proliferation-related signaling pathways, particularly the ERK and JNK MAPK pathways. Under conditions of oxidative damage, H7E prevents retinal cell death and reduces extracellular glutamate released from stressed Müller glia. In a mouse model of NMDA-induced retinal degeneration, H7E alleviated functional and structural defects within the inner retina as assessed by electroretinography and optical coherence tomography. Our results demonstrated that the newly identified compound H7E protects against glaucoma damage by specifically targeting HDAC8 activity in the retina. This protective effect is attributed to the inhibition of Müller glial activation and the prevention of retinal cell death caused by oxidative stress.
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Células Ependimogliais , Glaucoma , Inibidores de Histona Desacetilases , Histona Desacetilases , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Animais , Estresse Oxidativo/efeitos dos fármacos , Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , Glaucoma/patologia , Inibidores de Histona Desacetilases/farmacologia , Células Ependimogliais/efeitos dos fármacos , Células Ependimogliais/metabolismo , Células Ependimogliais/patologia , Camundongos , Histona Desacetilases/metabolismo , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/patologia , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Masculino , Degeneração Retiniana/tratamento farmacológico , Degeneração Retiniana/patologia , Degeneração Retiniana/metabolismo , Degeneração Retiniana/prevenção & controleRESUMO
Myeloperoxidase (MPO) is a member of the mammalian peroxidase superfamily and plays specific roles in host defense. This study aimed to explore the association between one polymorphism of MPO and hypertension risk. Study subjects were recruited from Taipei City Hospital, Zhongxiao Branch, Taipei Medical University Hospital and Taipei Municipal WanFang Hospital. Participants completed questionnaires and provided blood samples. In this study we considered hypertension to be present among subjects that had blood pressures above 140/90 mmHg, or who had previously received treatment for hypertension. The polymorphism of MPO investigated in this study was constructed by performing a restriction fragment length polymorphism following polymerase chain reaction. This study found the odds ratio and 95% confidence interval for hypertension among subjects with the MPO -463 GA/AA genotype to be 1.97 (1.23-3.16) when compared with those with the GG genotype after multivariate adjustment. Participants with a body mass index (BMI) ≥ 24 kg/m(2) and with MPO -463 GA/AA genotype had a 4.60-fold increased risk of hypertension compared with those with a BMI < 24 kg/m(2) and with the GG genotype. This is the first study to conclude that the MPO -463 GA/AA genotype was associated with hypertension. In addition, we also detected that subjects with the MPO -463 GA/AA genotype that had higher BMIs and positive diabetes status tended to have higher risks of hypertension than subjects with the MPO -463 GA/AA genotype that had normal BMIs and were not diabetic.
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Hipertensão/enzimologia , Hipertensão/genética , Peroxidase/genética , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Peroxidase/metabolismo , Polimorfismo Genético , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Background and objectives: Among individuals with Alzheimer's disease (AD), APOE e4 carriers with increased white matter hyperintensities (WMHs) may selectively be at increased risk of cognitive impairment. Given that the cholinergic system plays a crucial role in cognitive impairment, this study aimed to identify how APOE status modulates the associations between dementia severity and white matter hyperintensities in cholinergic pathways. Methods: From 2018 to 2022, we recruited participants (APOE e4 carriers, n = 49; non-carriers, n = 117) from the memory clinic of Cardinal Tien Hospital, Taipei, Taiwan. Participants underwent brain MRI, neuropsychological testing, and APOE genotyping. In this study, we applied the visual rating scale of the Cholinergic Pathways Hyperintensities Scale (CHIPS) to evaluate WMHs in cholinergic pathways compared with the Fazekas scale. Multiple regression was used to assess the influence of CHIPS score and APOE carrier status on dementia severity based on Clinical Dementia Rating-Sum of Boxes (CDR-SB). Results: After adjusting for age, education and sex, higher CHIPS scores tended to be associated with higher CDR-SB in APOE e4 carriers but not in the non-carrier group. Conclusions: Carriers and non-carriers present distinct associations between dementia severity and WMHs in cholinergic pathways. In APOE e4 carriers, increased white matter in cholinergic pathways are associated with greater dementia severity. In non-carriers, WMHs exhibit less predictive roles for clinical dementia severity. WMHs on the cholinergic pathway may have a different impact on APOE e4 carriers vs. non-carriers.
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Introduction: The microbiota-gut-brain axis is implicated in Alzheimer's disease. Gut microbiota alterations in mild cognitive impairment (MCI) are inconsistent and remain to be understood. This study aims to investigate the gut microbial composition associated with MCI, cognitive functions, and structural brain differences. Methods: A nested case-control study was conducted in a community-based prospective cohort where detailed cognitive functions and structural brain images were collected. Thirty-one individuals with MCI were matched to sixty-five cognitively normal controls by age strata, gender, and urban/rural area. Fecal samples were examined using 16S ribosomal RNA (rRNA) V3-V4 sequencing. Compositional differences between the two groups were identified and correlated with the cognitive functions and volumes/thickness of brain structures. Results: There was no significant difference in alpha and beta diversity between MCIs and cognitively normal older adults. However, the abundance of the genus Ruminococcus, Butyricimonas, and Oxalobacter decreased in MCI patients, while an increased abundance of nine other genera, such as Flavonifractor, were found in MCIs. Altered genera discriminated MCI patients well from controls (AUC = 84.0%) and were associated with attention and executive function. Conclusion: This study provides insights into the role of gut microbiota in the neurodegenerative process.