Risultati per: È confermato il legame tra la malattia di Alzheimer e microbiota intestinale

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Potenziale cura per cardiomiopatia amiloide da transtiretina

Objective
Cigarette smoking is a major risk factor for colorectal cancer (CRC). We aimed to investigate whether cigarette smoke promotes CRC by altering the gut microbiota and related metabolites.

Design
Azoxymethane-treated C57BL/6 mice were exposed to cigarette smoke or clean air 2 hours per day for 28 weeks. Shotgun metagenomic sequencing and liquid chromatography mass spectrometry were parallelly performed on mice stools to investigate alterations in microbiota and metabolites. Germ-free mice were transplanted with stools from smoke-exposed and smoke-free control mice.

Results
Mice exposed to cigarette smoke had significantly increased tumour incidence and cellular proliferation compared with smoke-free control mice. Gut microbial dysbiosis was observed in smoke-exposed mice with significant differential abundance of bacterial species including the enrichment of Eggerthella lenta and depletion of Parabacteroides distasonis and Lactobacillus spp. Metabolomic analysis showed increased bile acid metabolites, especially taurodeoxycholic acid (TDCA) in the colon of smoke-exposed mice. We found that E. lenta had the most positive correlation with TDCA in smoke-exposed mice. Moreover, smoke-exposed mice manifested enhanced oncogenic MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated protein kinase 1/2) signalling (a downstream target of TDCA) and impaired gut barrier function. Furthermore, germ-free mice transplanted with stools from smoke-exposed mice (GF-AOMS) had increased colonocyte proliferation. Similarly, GF-AOMS showed increased abundances of gut E. lenta and TDCA, activated MAPK/ERK pathway and impaired gut barrier in colonic epithelium.

Conclusion
The gut microbiota dysbiosis induced by cigarette smoke plays a protumourigenic role in CRC. The smoke-induced gut microbiota dysbiosis altered gut metabolites and impaired gut barrier function, which could activate oncogenic MAPK/ERK signalling in colonic epithelium.

Objective
Microbiome and dietary manipulation therapies are being explored for treating ulcerative colitis (UC). We aimed to examine the efficacy of multidonor faecal microbiota transplantation (FMT) and anti-inflammatory diet in inducing remission followed by long-term maintenance with anti-inflammatory diet in patients with mild-moderate UC.

Design
This open-labelled randomised controlled trial (RCT) randomised patients with mild-moderate (Simple Clinical Colitis Activity Index (SCCAI) 3–9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity (UCEIS) >1) on stable baseline medications in 1:1 ratio to FMT and anti-inflammatory diet (FMT-AID) versus optimised standard medical therapy (SMT). The FMT-AID arm received seven weekly colonoscopic infusions of freshly prepared FMT from multiple rural donors(weeks 0–6) with anti-inflammatory diet. Baseline medications were optimised in the SMT arm. Clinical responders (decline in SCCAI >3) at 8 weeks in both arms were followed until 48 weeks on baseline medications (with anti-inflammatory diet in the FMT-AID arm). Primary outcome measures were clinical response and deep remission (clinical—SCCAI

In Italia 3 milioni con problemi cronici. Studio con San Martino

Introduction
According to the World Alzheimer’s Report 2019, around 50 million people suffer from dementia, worldwide. Observational analysis revealed the existence of particular factors associated with the onset and progression of Alzheimer’s disease (AD). There are no international homogeneous principles for the early detection and evaluation of memory impairment and possible AD. This work aimed at (1) determining the prevalence of possible AD in the elderly residing in urban and rural regions in Cuba and (2) identifying the main factors that could significantly influence on its occurrence.

Methods and analysis
The study includes four neuropsychological tests (Clock Drawing Test, Mini-Mental Status Examination, Short Portable Mental Status Questionnaire, Cognitive and Non-Cognitive Alzheimer’s Disease Assessment Scale) and two scales (Clinical Dementia Rating and Global Deterioration Scale). Moreover, the protocol includes a survey with demographic and socioeconomic information, educational level, occupation, health, neuropsychological status of subjects, familial pathological history, comorbidities and lifestyles. The study will comprise a total of 1092 subjects aged ≥60, of both genders, and from every ethnic group settled in rural and urban areas. Primary outcomes: prevalence of possible AD. Secondary outcomes: correlation among risk and protective factors and AD, and comparison of the performance of neuropsychological tests and scales.

Ethics and dissemination
This research met the ethical codes of the Declaration of Helsinki. The Scientific Research Council of the Promoting Research Institute and the Ethics Committee of the Health Authorities approved the protocol. The proper written informed consent is also incorporated. The results of the survey will be published in scientific papers and shared with the Health Authorities of each municipality.

Rischio neurodegenerativo simile a Parkinson e Alzheimer

Circulation, Volume 146, Issue Suppl_1, Page A11528-A11528, November 8, 2022. Alzheimer’s disease (AD) is a complex and incurable neurodegenerative disorder characterized by cerebral amyloid β (Aβ) deposition and tau pathology, accompanied by a gradual loss of the two main neuromodulators, NGF and BDNF. The progressive degeneration of the cerebral neuro-signaling pathways triggers a gradual decline in neurotrophic factors with significant derangement of the peripheral nervous system. This may culminate in detrimental effects on other organs, including the heart. However, whether and how AD modulates neurotrophins, innervation, and amyloidosis in the cardiac tissue is still undefined. Here, we investigated, for the first time, cardiovascular remodeling and neuro signaling pathway dysregulation in a mouse model of Alzheimer’s disease. Hence, 12 months old Tg2576 transgenic mice, a model of cerebral amyloidosis, were compared to age-matched WT littermates. Echocardiographic analysis showed significant deterioration in LV function, evidenced by a severe decline both in ejection fraction and fraction shortening percentage in the Tg2576 group compared to WT mice. Tg2576 mice exhibited a relevant increase in interstitial fibrosis, with progressive accumulation of amyloid aggregates, resulting in severe cardiac nervous system dysfunction. The transgenic line showed a remarkable decrease in cardiac nerve fiber density, both adrenergic (stained with tyrosine hydroxylase- TH) and regenerating nerve endings (labeled with GAP-43) compared to the WT mice. This myocardial denervation was associated with a robust reduction in NGF and BDNF protein expression both at the neuronal and cardiac level, accompanied by a significant decline in GAP-43 activity in the heart and cerebral cortex lysates of Tg2576 mice. Additionally, human neuroblastoma cells (SH-SY5Y) challenged with human Aβ-40 or Aβ-42 oligomers showed a severe downregulation of both BDNF and GAP-43 protein levels. Overall, our evidence highlights a possible detrimental effect of cerebral amyloidosis on the peripheral nervous system and cardiac tissue, providing potential therapeutic targets, such as the neuro-signaling pathway, to prevent or delay some of the effects caused by AD on the cardiovascular system.

Circulation, Volume 146, Issue Suppl_1, Page A12707-A12707, November 8, 2022. Introduction:Contemporary HFrEF patients are older and have a higher prevalence of cognitive impairment compared to those studied in the original beta-blocker (BB) trials. While BB decrease mortality and morbidity in HFrEF, their use has been linked to higher fall risk and possibly acceleration of cognitive decline among older adults with Alzheimer’s Disease and Related Dementias (ADRD). The risk/benefit trade-off of beta blocker (BB) use in patients with HFrEF and dementia has not been examined.Methods:Using a 100% sample of patients enrolled in Medicare A, B and a 40% sample of D with ≥1 hospitalization for HFrEF between 2008 and 2018, we created a cohort of beneficiaries with HFrEF but no prior diagnosis of ADRD. We then subset to the population to those that developed ADRD in the year after their HFrEF hospitalization and compared BB use pre/post ADRD diagnosis and is association with outcomes using a time varying exposure.Results:The highest 1-year survival after ADRD diagnosis was observed among those continued on BB after ADRD diagnosis, regardless of whether they were on BB before (HR 0.427, 95% CI 0.406, 0.465, p

Circulation, Volume 146, Issue Suppl_1, Page A12300-A12300, November 8, 2022. Introduction:Phenylacetylglutamine (PAGln) has been recently discovered as a gut-microbiota-related metabolite, and circulating PAGln may be related to risks of cardiometabolic abnormalities. Gut microbiota-related dietary intakes and high-protein foods may affect circulating PAGln levels.Hypothesis:We assessed whether circulating PAGln levels may be related to intakes of gut-microbiota-related food intakes, and higher levels of PAGln may be associated with greater degrees of cardiometabolic abnormalities. We also tested a hypothesis that higher levels of circulating PAGln may be related to higher risk of the incident coronary heart disease (CHD).Methods:Circulating levels of PAGln, diet assessed using 7-day dietary records, and cardiometabolic abnormalities were assessed in the Women’s Lifestyle Validation Study (WLVS) (n=723). The associations between plasma PAGln levels and risk of incident CHD were analyzed in a prospective nested case-control of 1520 women (760 incident cases of fatal CHD and nonfatal myocardial infarction and 760 controls) from the Nurses’ Health Study (NHS). We identified incident cases of CHD over 10-14 years of follow-up time.Results:Higher levels of PAGln were associated with higher levels of circulating insulin, triglycerides, as well as lower levels of HDL cholesterol. We found that greater intakes of red meat and processed meat (p=0.01), but not of poultry or fish (p >0.05), and lower intakes of vegetables (p=0.03) were significant factors associated with higher levels of circulating PAGln. In the prospective nested case-control study setting, higher levels of PAGln were associated with higher risk of the incident CHD. Every 1 unit increment of log-transformed PAGln was associated with a relative risk of 1.21 (95% CI: 1.01, 1.45) for the incident CHD.Conclusions:Gut-microbiota-affecting diet quality were related to circulating levels of PAGln. Circulating PAGln levels may be associated with cardiometabolic abnormalities and risk of incident CHD among women.

Circulation, Volume 146, Issue Suppl_1, Page A11829-A11829, November 8, 2022. Introduction:Little is known about the outcomes of patients with Alzheimer’s disease (AD) following acute myocardial infarction (AMI).Methods:We used the 2017 National Inpatient Sample, including patients ages ≥60 with a primary diagnosis of STEMI and NSTEMI and those with any diagnostic code for AD. Any differences between AD and non-AD patients were calculated via Chi-square tests. The mortality rates of each group and their odds ratio (aOR) adjusted via multivariable logistic regression were also found.Results:A total of 104,860 cases of STEMI and 352,120 patients of NSTEMI were identified, amongst which 1,130 and 5,810 also had a diagnosis of Alzheimer’s disease. The incidence of Atrial flutter (160 cases, 1416 cases per 10,000 AD patients with STEMI), atrial fibrillation (320 cases, 2832 cases per 10,000 AD patients with STEMI), and long QT syndrome (15 cases, 133 cases per 10,000 AD patients with STEMI) for STEMI patients were higher among the AD patients (p

Accumulating evidence not only supports the functional role of the gut microbiome in cancer development and progression but also its role in defining the efficacy and toxicity of chemotherapeutic agents (5-fluorouracil, CTX, Irinotecan, Oxaliplatin, Gemcitabine, Methotrexate) and immunotherapeutic (anti-PD-L1/ anti-PD-1 and anti-CTLA-4) compounds. This evidence is supported in numerous in-vitro, animal and clinical studies which highlight the importance of microbial mechanisms in defining therapeutic responses.

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