The aim was to assess the effects of
(AN) with/without
C-3102 as alternative treatments for Chronic Inflammatory Enteropathy (CIE) of dogs. Fourteen CIE patients, which had received the same control ...(CTR) diet, were enrolled to serially receive three diets: (1) hydrolysed protein (HP) diet; (2) 4.0% AN supplemented HP (HPA) food, (3) HPA diet fortified with 125 billion
C-3102 spores/10 kg body weight (HPAB diet). Clinical outcome was assessed by Canine Inflammatory Bowel Disease Activity Index (CIBDAI), whereas gut microbiota compositional variations were investigated via 16S rRNA gene analysis, and faecal fermentation end-products by liquid chromatography. Higher abundances of the
and
families were shown in HPA relative to CTR treatment, with
genus being differentially abundant on HPAB diet. Concentrations of acetate were higher (
< 0.05) in dogs fed HPA compared to CTR diet, and amounts of isovalerate and isobutyrate were greater (
< 0.05) in HPA compared to HP food. A tendency for higher amounts of faecal butyrate was found for the HPAB treatment (
= 0.06). Comprehensively, while displaying potentially positive effects on faecal fermentations, the tested substances failed to improve CIBDAI scores and microbial richness in CIE dogs.
Treatment with low-dose ozone is successfully exploited as an adjuvant therapy in the treatment of several disorders. Although the list of medical applications of ozone therapy is increasing, ...molecular mechanisms underlying its beneficial effects are still partially known. Clinical and experimental evidence suggests that the therapeutic effects of ozone treatment may rely on its capability to mount a beneficial antioxidant response through activation of the nuclear factor erythroid-derived-like 2 (Nrf2) pathway. However, a conclusive mechanistic demonstration is still lacking. Here, we bridge this gap of knowledge by providing evidence that treatment with a low concentration of ozone in cultured cells promotes nuclear translocation of Nrf2 at the chromatin sites of active transcription and increases the expression of antioxidant response element (ARE)-driven genes. Importantly, we show that ozone-induced ARE activation can be reverted by the ectopic expression of the Nrf2 specific inhibitor Kelch-like ECH associated protein (Keap1), thus proving the role of the Nrf2 pathway in the antioxidant response induced by mild ozonisation.
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•Low ozone concentrations induce increases nuclear translocation of Nrf2 at the transcriptional sites.•Low ozone concentrations activate ARE-driven transcription in a dose-dependent manner.•Low ozone concentrations trigger an antioxidant response through activation of the Nrf2/Keap1-dependent pathway.
Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of ...Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before.
HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195).
During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported.
PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time.
In lower extremity peripheral artery disease (PAD), the ankle-brachial index (ABI) is an easily reproducible diagnostic tool for PAD, but it loses reliability when > 1.4 due to calcification of the ...vessel wall. Patients with diabetes are at higher risk for wall calcification. In order to overcome the limitation and reliability of ABI, particularly in patients with diabetes, we decided to assess resistive (RI) and pulsatility index (PI) by ultrasound doppler of the dorsal metatarsal artery (DMA).
We therefore analyzed 51 legs (32 patients), evaluating the correlation between PI, RI, and ABI. Patients with diabetes were 21 (65.6 %), accounting for 33 legs (64.7 %). Out of 51 legs assessed, 37 (72.5 %) cases had compressible arteries, whereas in 14 legs (27.5 %) ABI was not calculable due to wall calcification. PAD was significantly associated with lower both RI and PI of the DMA (both p < 0.000). RI, but not PI, showed a significant correlation (r = 0.535) with ABI, when ABI was less than 1.4, but not when ABI > 1.4. When analyzed separately, patients with diabetes showed a similar figure in comparison with those without diabetes (r = 0.600), RI, but not PI, showed a significant correlation with ABI.
Dorsal metatarsal artery resistive index (MARI) showed a significant inverse correlation with PAD, similarly to ABI, irrespective of the presence of diabetes. MARI seems to be an effective screening tool for PAD even in patients with wall calcification. Further studies are needed for confirming the results of the present pilot study.
Coffee and Microbiota: A Narrative Review Rosa, Federico; Marigliano, Benedetta; Mannucci, Sergio ...
Current Issues in Molecular Biology,
01/2024, Letnik:
46, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Coffee is one of the most widely consumed beverages in the world, which has important repercussions on the health of the individual, mainly because of certain compounds it contains. Coffee ...consumption exerts significant influences on the entire body, including the gastrointestinal tract, where a central role is played by the gut microbiota. Dysbiosis in the gut microbiota is implicated in the occurrence of numerous diseases, and knowledge of the microbiota has proven to be of fundamental importance for the development of new therapeutic strategies. In this narrative review, we thoroughly investigated the link between coffee consumption and its effects on the gut microbiota and the ensuing consequences on human health. We have selected the most significant articles published on this very interesting link, with the aim of elucidating the latest evidence about the relationship between coffee consumption, its repercussions on the composition of the gut microbiota, and human health. Based on the various studies carried out in both humans and animal models, it has emerged that coffee consumption is associated with changes in the gut microbiota, although further research is needed to understand more about this link and the repercussions for the whole organism.
Aim of the present network meta-analysis (NMA) is the comparison across glucose-lowering drugs (GLA) concerning their effects on glucose control, body weight, hypoglycemia, gastrointestinal adverse ...events, and quality of life.
This NMA includes randomized clinical trials comparing different head-to-head comparison trials with EMA-approved GLA in type 2 diabetes, with a duration of ≥52 weeks. All drugs have to be administered at the maximal approved dose. Primary endpoints were HbA1c at 12, 52, and 104+ weeks. Secondary endpoints were body weight, quality of life, hypoglycemia, and gastrointestinal disorders. Indirect comparisons of different GLA were performed by NMA choosing metformin as reference. The standardized difference in means (SDM) and Mantel-Haenzel Odds Ratio MH–OR (using random-effect models) with 95% Confidence Intervals were calculated for categorical and continuous variables, respectively.
We included 68 trials fulfilling all inclusion criteria. At 12 weeks, when considering indirect comparisons, insulin secretagogues (IS) were associated with a significantly greater reduction in comparison with metformin (SDM, −0.3 -0.4;-0.2%); a significantly lower efficacy was observed for pioglitazone. At 52 weeks, IS were no longer associated with a greater reduction of HbA1c; whereas a significant decrease in HbA1c was observed for GLP-1 RA (SDM, −0.2 -0.1;-0.3%). At 104+ weeks, only SGLT-2 inhibitors showed a significantly greater HbA1c reduction (SDM, −0.2 -0.1;-0.3%), whereas sulfonylureas and insulin showed a significantly lower efficacy (SDM, 0.1 0.0; 0.2%), and 0.4 0.3; 0.5%, respectively).
The results of this meta-analysis should be considered together with evidence on long-term outcomes for selecting the most appropriate drugs for individual patients.
•Different classes of drugs have different effects on glucose control depending to the length of treatment.•Sulfonylureas were effective drugs in the short term, but less effective when increasing the duration of treatment.•SGLT2 inhibitors and GLP-1 RA were the most effective drugs in the longer term.
Cities are experiencing an increased rate of climate-related extreme events threats derived from climate change. Floods are one of the most challenging issues to address to reduce damages and losses ...in urban areas. Building resilience through adaptation to these changing conditions has become a common goal for different disciplines involving planning for the future. Adaptation planning is widely recognized as generally applicable to any field. However, there are current limitations to overcome for architectural and urban planning to switch from theory to practice. This paper proposes a critical overview of literature works on flood mitigative strategies and adaptive approaches considering uncertainties, linking strategies for the Built Environment (BE) to mitigate the effects of floods, and operative frameworks to pursue adaptation under changing environmental conditions. The literature selection accounts for the pivotal components of the BE: open spaces (OSs), buildings, and users. Next, we provide an overview of the most relevant adaptive methodologies that have emerged in literature, and, lastly, the planning strategies are discussed, considering the climate-related uncertainties that might undermine the effectiveness of the designed action. The present paper aimed to provide a contribution to the discussion regarding the necessity of making architectural and urban planning adaptive, providing a base for future studies for operative adaptation.
Surveillance programs on high-risk individuals (HRIs) can detect pre-malignant lesions or early pancreatic cancer (PC). We report the results of the first screening round of the Italian multicenter ...program supported by the Italian Association for the study of the Pancreas (AISP).
The multicenter surveillance program included asymptomatic HRIs with familial (FPC) or genetic frailty (GS: BRCA1/2, p16/CDKN2A, STK11/LKB1or PRSS1, mutated genes) predisposition to PC. The surveillance program included at least an annual magnetic resonance cholangio pancreatography (MRCP). Endoscopic ultrasound (EUS) was proposed to patients who refused or could not be submitted to MRCP.
One-hundreds eighty-seven HRIs underwent a first-round screening examination with MRCP (174; 93.1%) or EUS (13; 6.9%) from September 2015 to March 2018.The mean age was 51 years (range 21-80).One-hundreds sixty-five (88.2%) FPC and 22 (11.8%) GF HRIs were included. MRCP detected 28 (14.9%) presumed branch-duct intraductal papillary mucinous neoplasms (IPMN), 1 invasive carcinoma/IPMN and one low-grade mixed-type IPMN, respectively. EUS detected 4 PC (2.1%): 1 was resected, 1 was found locally advanced intraoperatively, and 2 were metastatic. Age > 50 (OR 3.3, 95%CI 1.4-8), smoking habit (OR 2.8, 95%CI 1.1-7.5), and having > 2 relatives with PC (OR 2.7, 95%CI 1.1-6.4) were independently associated with detection of pre-malignant and malignant lesions. The diagnostic yield for MRCP/EUS was 24% for cystic lesions. The overall rate of surgery was 2.6% with nil mortality.
The rate of malignancies found in this cohort was high (2.6%). According to the International Cancer of the Pancreas Screening Consortium the screening goal achievement was high (1%).
Summary Beclin 1 and LC3 autophagic genes are altered in several human cancer types. This study was designed to assess the expression of Beclin 1 and LC3 in cutaneous melanocytic lesions, in which ...they have not yet been investigated. In melanoma, we correlated their expression with conventional histopathologic prognostic factors. In 149 lesions, including benign nevi, dysplastic nevi, radial growth phase melanomas, vertical growth phase melanomas, and melanoma metastases, proteins were evaluated by immunohistochemistry, and, in representative cases of benign nevi, vertical growth phase melanomas and melanoma metastases were evaluated by Western blotting. In most lesions, messenger RNA level was also assessed by real-time reverse transcriptase polymerase chain reaction. Both genes were expressed in all the investigated conditions. Beclin 1 cytoplasmic protein and messenger RNA, as well as LC3 messenger RNA, significantly decreased with tumor progression ( P < .05). The percentage of cases with high cytoplasmic expression of beclin 1 from 100% in benign nevi declined to 86.4% in dysplastic nevi, 54.5% in radial growth phase melanomas, 54.3% in vertical growth phase melanomas, and 26.7% in melanoma metastases. The lowest expression of LC3 II protein was observed in melanoma metastases (53.3% of cases) ( P < .05); LC3 II protein overexpression was, however, found in several nonbenign lesions, with the highest percentage (45.5%) in radial growth phase melanomas. LC3 II protein expression was inversely correlated to thickness, ulceration, and mitotic rate. In a multivariate analysis, messenger RNAs for both genes discriminated between nonmalignant (benign and dysplastic nevi) and malignant (radial, vertical growth phase melanomas, and melanoma metastases) lesions. Our results, therefore, indicate that beclin 1 and LC3 II autophagic gene expression is altered also in melanocytic neoplasms.
Background:The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC) autotransplantation in critical limb ischemia (CLI) has been reported. Variable proportions of circulating monocytes ...express low levels of CD34 (CD14+CD34lowcells) and behave in vitro as endothelial progenitor cells (EPCs). The aim of the present randomized clinical trial was to compare the safety and therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral blood by immunomagnetic selection of CD14+and CD34+cells) or BM-MNC were injected into the gastrocnemius of the affected limb in 23 and 17 patients, respectively. After a mean of 25.2±18.6-month follow-up, both groups showed significant and progressive improvement in muscle perfusion (primary endpoint), rest pain, consumption of analgesics, pain-free walking distance, wound healing, quality of life, ankle-brachial index, toe-brachial index, and transcutaneous PO2. In ECEPC-treated patients, there was a positive correlation between injected CD14+CD34lowcell counts and the increase in muscle perfusion. The safety profile was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the number of deaths and major amputations was lower compared with eligible untreated patients and historical reference patients.Conclusions:This study supports previous trials showing the efficacy of BM-MNC autotransplantation in CLI patients and demonstrates comparable therapeutic efficacy between BM-MNC and EPEPCs.
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