Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the world, yet the pathogenesis of the disease is not well elucidated. Due to the close anatomic and functional ...association between the intestinal lumen and the liver through the portal system, it is speculated that the gut microbiome may play a pivotal role in the pathogenesis of NAFLD. Furthermore, diet, which can modulate the gut microbiome and several metabolic pathways involved in NAFLD development, shows a potential tripartite relation between the gut, diet, and the liver. In this review, we summarize the current evidence that supports the association between NAFLD, the gut microbiome, and the role of diet.
Abstract
Medulloblastoma is the most common high-grade brain tumor in childhood. Medulloblastomas with c-myc amplification, classified as group 3, are the most aggressive among the four disease ...subtypes resulting in a 5-year overall survival of just above 50%. Despite current intensive therapy regimens, patients suffering from group 3 medulloblastoma urgently require new therapeutic options. Using a recently established c-myc amplified human medulloblastoma cell line, we performed an in-vitro-drug screen with single and combinatorial drugs that are either already clinically approved or agents in the advanced stage of clinical development. Candidate drugs were identified in vitro and then evaluated in vivo. Tumor growth was closely monitored by BLI. Vessel development was assessed by 3D light-sheet-fluorescence-microscopy. We identified the combination of gemcitabine and axitinib to be highly cytotoxic, requiring only low picomolar concentrations when used in combination. In the orthotopic model, gemcitabine and axitinib showed efficacy in terms of tumor control and survival. In both models, gemcitabine and axitinib were better tolerated than the standard regimen comprising of cisplatin and etoposide phosphate. 3D light-sheet-fluorescence-microscopy of intact tumors revealed thinning and rarefication of tumor vessels, providing one explanation for reduced tumor growth. Thus, the combination of the two drugs gemcitabine and axitinib has favorable effects on preventing tumor progression in an orthotopic group 3 medulloblastoma xenograft model while exhibiting a favorable toxicity profile. The combination merits further exploration as a new approach to treat high-risk group 3 medulloblastoma.
This study is to determine the effect of the family-centered intervention (FCIS) on the key indicators of diabetes management and Control control in patients with type-2 diabetes.
The present study ...is a quiz- experimental study with a randomized control group. Participants were 64 patients with type-2 diabetes visiting Ali Asghar Hospital of Isfahan in 2018. The eligible patients were assigned to either the intervention group or the control group (i.e., patient-center care) through block randomization. FCIS were implemented in 4 two-hour sessions as home visits while the patients and their caregivers were present. Data were collected twice-
. before the intervention and 12 weeks after it- and were analyzed, by running a t-test (α = 0.05), using SPSS-21.
The mean ± SD age of participants was 50.4 ± 8.5. There was no significant difference between the two groups in the mean weight, serum levels of FBS and A1C, physical activity, energy intake, and BMI before intervention. But, a significant improvement in the mean values of these variables in the intervention group after the intervention, compared with the control group was indicated (
< 0.05).
This study suggests that FCIS are more effective than patient-center care in the management and control of type-2 diabetes. Therefore, it is recommended that the family be considered in educational interventions.
Multiple myeloma remains a largely incurable disease of clonally expanding malignant plasma cells. The bone marrow microenvironment harbors treatment-resistant myeloma cells, which eventually lead to ...disease relapse in patients. In the bone marrow, CD4
FoxP3
regulatory T cells (Tregs) are highly abundant amongst CD4
T cells providing an immune protective niche for different long-living cell populations, e.g., hematopoietic stem cells. Here, we addressed the functional role of Tregs in multiple myeloma dissemination to bone marrow compartments and disease progression. To investigate the immune regulation of multiple myeloma, we utilized syngeneic immunocompetent murine multiple myeloma models in two different genetic backgrounds. Analyzing the spatial immune architecture of multiple myeloma revealed that the bone marrow Tregs accumulated in the vicinity of malignant plasma cells and displayed an activated phenotype. In vivo Treg depletion prevented multiple myeloma dissemination in both models. Importantly, short-term in vivo depletion of Tregs in mice with established multiple myeloma evoked a potent CD8 T cell- and NK cell-mediated immune response resulting in complete and stable remission. Conclusively, this preclinical in-vivo study suggests that Tregs are an attractive target for the treatment of multiple myeloma.
Background: Over the last decade, an emerging role of novel cytokines in the pathogenesis of gestational diabetes mellitus (GDM) has been proposed. The present study was implemented to provide a more ...accurate estimate of the effect size of the association between leptin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and the risk of GDM.Methods: Online databases were looked up to January 2023 using the search string: (leptin OR TNF-α OR IL-6) AND "gestational diabetes." Observational studies investigating the association of selected cytokines and GDM risk were included. Odds ratios and their 95% confidence intervals (CIs) were extracted and random-effects models were used to estimate the pooled effect.Results: Twenty-four studies were included in the meta-analysis. A significant association was found between higher circulating leptin and the risk of GDM and the pooled estimate was 1.16 (95%CI: 1.07, 1.27). Higher circulating levels of IL-6 and TNF-α were associated with increased risk of GDM, and the pooled estimates were 1.35 (95%CI: 1.05, 1.73) and 1.28 (95%CI: 1.01, 1.62), respectively.Conclusions: The studied cytokines could be implicated in the GDM pathogenesis and used as potential biomarkers for assessing the GDM risk. Additional longitudinal studies with large sample sizes are needed for a further evaluation of these findings.
In this study, we assessed the risk of cardiovascular diseases (CVDs) and all-cause mortality in subjects having an only physical activity or a healthy diet or both compared to those having none of ...these healthy behaviors in the Golestan Cohort Study (GCS). A total of 50,045 participants aged greater than or equal to 40 years were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a median of 13.9 years. Four lifestyles were compared: healthy diet and active (HDA), healthy diet but inactive (HDI), unhealthy diet but active (UDA), and unhealthy diet and inactive (UDI), with UDI being considered as the reference group. Diet quality was assessed by the Dietary Approaches to Stop Hypertension diet score, which was calculated based on a validated food frequency questionnaire. The primary outcomes were death from any cause and CVDs. Adjusted Cox models were used to estimate the hazards ratio (HR) and 95% confidence intervals (CI) for overall and CVDs mortality. During 467,401 person-years of follow-up, 6,256 overall deaths and 2,043 confirmed CVDs deaths were reported. After adjustment for potential confounders, there was a significant lower risk for all-cause mortality in participants with both healthy behaviors (HR = 0.79, 95% CI = 0.73 to 0.86) or only one healthy behavior HDI: HR = 0.84, 95% CI = 0.78 to 0.90) and UDI: HR = 0.91, 95% CI = 0.85 to 0.97 compared to those with both unhealthy behaviors. For CVDs mortality, the HDA lifestyle (HR = 0.74, 95%CI = 0.65 to 0.86), as well as the UDA lifestyle (HR = 0.83, 95%CI = 0.74 to 0.94) indicated a significant lower risk compared to the UDI lifestyle. The HDI lifestyle was not more effective than UDI. The greatest reduction in all-cause and CVDs mortality was related to the HDA. For all-cause mortality, both HDI and UDA lifestyles were associated with a decreased risk in comparison to UDI, but for CVDs mortality, only UDA but not HDI decreased the risk.
Physical activity has benefits for the cardiovascular system, however, what levels and types of activity provide optimal cardiovascular health is unclear. We aimed to determine the level of physical ...activity that has the most benefits against cardiovascular diseases (CVD).
PubMed, Scopus, and Web of Science were searched for prospective cohort studies on leisure-time (LTPA) or occupational physical activity (OPA) as the exposure and major types of CVD (total CVD, coronary heart disease CHD, stroke, and atrial fibrillation AF) incidence as the outcome. Risk of bias of studies was evaluated using the ROBINS-I tool. Summary hazard ratios (HR) were calculated using random-effects pairwise model.
A total of 103 studies were included in the analysis. The highest versus the lowest LTPA was associated with a lower risk of overall CVD (HR = 0.81; 95% CI: 0.77-0.86), CHD (HR = 0.83; 0.79-0.88), and stroke (HR = 0.83; 0.79-0.88), but not AF (HR = 0.98; 0.92-1.05). Linear dose-response analyses showed a 10%, 12%, 9%, and 8% risk reduction in CVD, CHD, stroke, and AF incidence, respectively, for every 20 MET-hours/week increase in LTPA. In nonlinear dose-response analyses, there were inverse associations up to 20 MET-hours/week with 19% and 20% reduction in CVD and CHD risk, and up to 25 MET-hours/week with 22% reduction in stroke, with no further risk reduction at higher LTPA levels. For AF, there was a U-shaped nonlinear association with the maximum 8% risk reduction at 10 MET-hours/week of LTPA. Higher levels of OPA were not associated with risk of CVD, CHD, stroke, or AF.
Overall, results showed an inverse dose-response relationship between LTPA and risk of CVD, CHD, stroke, and AF. Running was the most beneficial LTPA but the risk was similar among various LTPA intensities. OPA showed no benefits in total or any type of CVD.
Clinical studies suggested that endothelial dysfunction and damage could be involved in the development and severity of acute graft-versus-host disease (aGVHD). Accordingly, we found increased ...percentage of apoptotic Casp3+ blood vessels in duodenal and colonic mucosa biopsies of patients with severe aGVHD. In murine experimental aGVHD, we detected severe microstructural endothelial damage and reduced endothelial pericyte coverage accompanied by reduced expression of endothelial tight junction proteins leading to increased endothelial leakage in aGVHD target organs. During intestinal aGVHD, colonic vasculature structurally changed, reflected by increased vessel branching and vessel diameter. Because recent data demonstrated an association of endothelium-related factors and steroid refractory aGVHD (SR-aGVHD), we analyzed human biopsies and murine tissues from SR-aGVHD. We found extensive tissue damage but low levels of alloreactive T cell infiltration in target organs, providing the rationale for T-cell independent SR-aGVHD treatment strategies. Consequently, we tested the endothelium-protective PDE5 inhibitor sildenafil, which reduced apoptosis and improved metabolic activity of endothelial cells in vitro. Accordingly, sildenafil treatment improved survival and reduced target organ damage during experimental SR-aGVHD. Our results demonstrate extensive damage, structural changes, and dysfunction of the vasculature during aGVHD. Therapeutic intervention by endothelium-protecting agents is an attractive approach for SR-aGVHD complementing current anti-inflammatory treatment options.
Cell migration is the driving force behind the dynamics of many diverse biological processes. Even though microscopy experiments are routinely performed today by which populations of cells are ...visualized in space and time, valuable information contained in image data is often disregarded because statistical analyses are performed at the level of cell populations rather than at the single-cell level. Image-based systems biology is a modern approach that aims at quantitatively analyzing and modeling biological processes by developing novel strategies and tools for the interpretation of image data. In this study, we take first steps towards a fully automated characterization and parameter-free classification of cell track data that can be generally applied to tracked objects as obtained from image data. The requirements to achieve this aim include: (i) combination of different measures for single cell tracks, such as the confinement ratio and the asphericity of the track volume, and (ii) computation of these measures in a staggered fashion to retrieve local information from all possible combinations of track segments. We demonstrate for a population of synthetic cell tracks as well as for in vitro neutrophil tracks obtained from microscopy experiment that the information contained in the track data is fully exploited in this way and does not require any prior knowledge, which keeps the analysis unbiased and general. The identification of cells that show the same type of migration behavior within the population of all cells is achieved via agglomerative hierarchical clustering of cell tracks in the parameter space of the staggered measures. The recognition of characteristic patterns is highly desired to advance our knowledge about the dynamics of biological processes.
Purpose
To assess serum vitamin D trend from baseline to 12 months after one anastomosis gastric bypass (OAGB).
Materials and Methods
In this observational cohort analysis of longitudinal data, we ...assessed the trend of serum vitamin D, and its associations with anthropometric, and biochemical measurements in 98 patients undergoing OAGB in a bariatric surgery center. All participants were on >800 IU/day vitamin D supplementation.
Results
Vitamin D, lipid profile, creatinine, and albumin levels significantly improved at 12 months post-surgery. Vitamin D concentrations significantly increased from 26.52 ± 12.32 to 54.52 ± 27.90 ng/mL at 12 months. The correlations between vitamin D concentrations and weight, body mass index, lipid profile, ferritin, glycemic indices, and albumin were not significant. In addition, the correlations between vitamin D and parathormone, vitamin D receptor, calcium, phosphorus, body composition, and basal metabolic rate (BMR) did not reach the threshold of statistical significance at 12 months following bariatric surgery. Although there was a significant correlation between body weight and body composition (
P
< 0.001) and basal metabolic rate (BMR) (
r
= 0.762,
P
< 0.001) at 12 months, there were no significant correlations between weight change percent and body composition (
P
> 0.05), BMR (
r
= −0.101,
P
= 0.350), and vitamin D (
r
= 0.120,
P
= 0.271) at 12 months.
Conclusion
Our results showed that supplementation of vitamin D with dosage of >800 IU/day is sufficient for prevention of vitamin D deficiency within 12 months after OAGB surgery.
Graphical abstract
Note: This data is mandatory.
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