Short-term EXE therapy was linked to significant weight loss and central adiposity reduction, which may further explain the improvements in insulin resistance, inflammatory marker and menstrual cycle, which may contribute to increasing pregnancy rates in OW/OB women with PCOS.
The MiT/TFE transcription factors play a pivotal role in the regulation of autophagy and lysosomal biogenesis. The subcellular localization and activity of MiT/TFE proteins are primarily regulated through phosphorylation. And the phosphorylated protein is retained in the cytoplasm and subsequently translocates to the nucleus upon dephosphorylation, where it stimulates the expression of hundreds of genes, leading to lysosomal biogenesis and autophagy induction. The transcription factor-mediated lysosome-to-nucleus signaling can be directly controlled by several signaling molecules involved in the mTORC1, PKC, and AKT pathways. MiT/TFE family members have attracted much attention owing to their intracellular clearance of pathogenic factors in numerous diseases. Recently, multiple studies have also revealed the MiT/TFE proteins as master regulators of cellular metabolic reprogramming, converging on autophagic and lysosomal function and playing a critical role in cancer, suggesting that novel therapeutic strategies could be based on the modulation of MiT/TFE family member activity. Here, we present an overview of the latest research on MiT/TFE transcriptional factors and their potential mechanisms in cancer.
Introduction
Helicobacter pylori
eradication therapy may lead to the perturbation of gut microbiota. We aim to investigate the impact of probiotics on eradication rate and gut microbiota during eradication therapy.
Methods
A total of 162 patients receiving bismuth quadruple therapy were enrolled and randomly assigned to groups given probiotics (
n
= 83) or placebo (
n
= 79) for 4 weeks. Fecal samples were collected before treatment and 2, 4, 6, and 8 weeks after eradication therapy. Gut microbiota was analyzed by 16S rRNA high-throughput sequencing.
Results
The eradication rates in the placebo and probiotics group were 82.43% and 87.01%, respectively (
P
> 0.05). Compared with baseline, alpha and beta diversity was significantly altered 2 weeks after eradication in both groups, which was restored at week 8. There were no significant differences in diversity between the two groups.
H. pylori
eradication therapy resulted in enrichment of some detrimental bacteria taxa such as
Shigella
,
Klebsiella
, and
Streptococcus
, while probiotics supplementation could rapidly restore these taxa levels after eradication and increase the taxa of
Bacillus
and Lactobacillales. Functional analysis revealed that lipopolysaccharide biosynthesis and polymyxin resistance pathways were significantly enriched after eradication, while probiotics supplementation mainly enriched the cofactors and vitamins metabolism pathways. Increased relative abundances of
Roseburia
and
Dialister
were associated with the positive eradication outcome.
Conclusions
Probiotics supplementation might help to construct a beneficial profile of gut microbiota after eradication therapy. Specific bacteria taxa are associated with
H. pylori
eradication outcome. These findings may be of value in rational use of probiotics during
H. pylori
eradication.
Trial Registration
Chinese Clinical Trial Registry, ChiCTR1900022116.
Electronic supplementary material
The online version of this article (10.1007/s40121-020-00372-9) contains supplementary material, which is available to authorized users.
AimPremixed insulin regimens are commonly used for the treatment of patients with type-2 diabetes mellitus (T2DM). However, limited data are available regarding next-step therapy options in cases where premixed insulin fails to provide adequate glycemic control. This 20-week observational study of everyday clinical practice evaluated the efficacy, safety and treatment satisfaction of insulin glargine plus oral anti-diabetic drugs (OADs) in T2DM patients previously treated with premixed insulin.MethodsIn this open-label, single-arm, 20-week study, 70 subjects with T2DM inadequately controlled with premixed insulin were switched to insulin glargine plus OADs. Changes in glycaemic control, incidence of hypoglycaemia, treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (DTSQ), serum superoxide dismutase (SOD), and serum 8-iso-prostaglandin (8-iso-PG) were evaluated at the start and the end of the study.ResultsOver the 20 week treatment period, mean (±SD) HbA1c levels decreased from 8.28 ± 1.24% to 6.83 ± 1.09%, mean (±SD) FBG levels decreased from 7.64 ± 1.36 mmol/L to 5.57 ± 1.21 mmol/L, and 2 h PBG levels decreased from 12.07 ± 1.17 mmol/L to 8.94 ± 1.56 mmol/L, all P < 0.001. A total of 3 symptomatic hypoglycemic episodes were reported. No significant reductions in body weight were observed. The mean daily dose of insulin decreased by 14 U between week 0 (30.20 ± 9.93 U) and week 20 (16.38 ± 5.15 U). The total treatment satisfaction score showed a significant increase from study baseline to end point. Significant increases in SOD(90.00 ± 16.62 to 108.81 ± 27.02 u/ml, P < 0.01) and reductions in 8-iso-PG(2.15 ± 0.61 to 1.64 ± 0.42 pg/ml, P < 0.05) were observed between the start and end of the observation period. There were significant differences in baseline HbA1c, duration of diabetes, and baseline postprandial C-peptide between the A1c ≤ 6.5% group and the A1c > 7.0% group [HbA1c: 7.25% ± 1.02% vs. 9.32% ± 1.23%; duration: 7.84 ± 1.02 vs. 13.96 ± 1.35 years; postprandial C-peptide: 4.83 ± 2.11 vs 2.54 ± 0.87 nmol/L, all P < 0.05].ConclusionsThe observational study shows that, in T2DM patients inadequately controlled with premixed insulin, switching therapy to glargine plus OADs is associated with significant improvements in glycaemic control and treatment satisfaction, and is with low incidence of hypoglycemia. Baseline postprandial C-peptide, HbA1c, and duration of diabetes are the key factors closely related to efficacy of this treatment regimen.
Key Points
Question
Can artificial intelligence be applied in video review of small bowel capsule endoscopy (SBCE)?
Findings
In this diagnostic study of 5825 patients, a convolutional neural network solution was developed based on CE structured terminology (CEST) to allow a standardized computer-aided detection (CADe) approach. The convolutional neural network was associated with an increased detection rate of SB findings and reduced SBCE video reading times.
Meaning
This study suggests that a well-structured CADe algorithm, based on CEST, may change the human-based reading and reporting of SBCE videos.
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