Inflammatory bowel disease (IBD), which consists of Crohn's disease (CD) and ulcerative colitis (UC), is a chronic, inflammatory disorder of the gastro-intestinal tract with unknown etiology. Current ...evidence suggests that intestinal epithelial cells (IECs) is prominently linked to the pathogenesis of IBD. Therefore, maintaining the intact of epithelium has potential roles in improving pathophysiology and clinical outcomes of IBD. MicroRNAs (miRNAs) act as post-transcriptional gene regulators and regulate many biological processes, including embryonal development, cell differentiation, apoptosis and proliferation. In this study, we found that miR-200b decreased significantly in inflamed mucosa of IBD, especially for UC, when compared with their adjacent normal tissue. Simultaneously, we also found that the genes of E-cadherin and cyclin D1 were reduced significantly and correlated positively to the miR-200b. In addition, the upregulation of transforming growth factor-beta 1 (TGF-β1) was inversely correlated to the miR-200b in IBD. To investigate the possible roles of miR-200b in IECs maintaining, we used TGF-β1 to induce epithelial-mesenchymal transition (EMT) in IEC-6 initially. After sustained over-expressing miR-200b in IEC-6, the EMT was inhibited significantly that was characterized by downregulation of vimentin and upregulation of E-cadherin. Furthermore, we found that miR-200b enhanced E-cadherin expression through targeting of ZEB1, which encode transcriptional repressors of E-cadherin. SMAD2 was found to act as a target of miR-200b with direct evidence that miR-200b binding to the 3' UTR of SAMD2 and the ability of miR-200b to repress SMAD2 protein expression. With SMAD2 depletion, the expression of vimentin decreased correspondingly, which suggested miR-200b might reduce vimentin through regulating the SMAD2. With endogenous over-expression of miR-200b, the proliferation of IEC-6 cells increased significantly by increasing S-phase entry and promoting expression of the protein cyclin D1. Summarily, our study suggested a potential role for mir-200b in maintaining intact of intestinal epithelium through inhibiting EMT and promoting proliferation of IECs.
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•Magnetron sputtering was used to fabricate Al films.•High coercivity and excellent corrosion resistance were obtained.•A weak ferromagnetic phase within intergranular phase was ...investigated.
Al film, which was coated in sintered Nd-Fe-B magnets prepared by magnetron sputtering, was employed for grain boundary diffusion source. Effects of the grain boundary diffusion processes (GBDP) on the microstructure evolution and properties were investigated in detail. Through grain boundary diffusion processes, the highest coercivity of 1184 kA/m and maximum energy product of 238 kJ/m3 could be obtained, increasing by 21.8% and 3.9%, respectively, compared with the initial magnet. Meanwhile, our results showed that fine, uniform and continuous intergranular phase induced by Al diffusion, was the main reason for properties improvement, while a weak ferromagnetic phase and the vague interface between main phase and RE-rich phase should be responsible to the deterioration of coercivity when the diffused temperature exceed 600 °C. Besides, the corrosion resistance of Al-diffused magnets was also greatly improved, owing to the fact that the Al element could promote the electrochemical potential of RE-rich phase and the more thin, continuous intergranular phase would also narrow the corrosion channel.
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Evasion of apoptosis is fundamental to the pathogenesis of cancer. Members of the B-cell Lymphoma 2 (BCL-2) protein family are key pro- and anti-apoptotic regulators, and in healthy ...cells are held in a fine, delicate balance – perturbations of which may tip a cell irreversibly towards cellular death or, conversely, allow a cell to permanently escape apoptosis and immortalize itself as a malignant clone. The restoration of this balance or, indeed, adjustment in favor of apoptosis via manipulation of the BCL-2 family, is a promising area in the realm of molecular therapeutics, and one in which breathtaking advances are currently being made. The purpose of this review is to outline the role of the BCL-2 family in apoptosis, to contrast its optimal functioning with those disruptions seen in malignancy, and to provide an overview of the medications both presently available and currently under development which selectively target members of this family.
High-fat diet (HFD) decreases insulin sensitivity. How high-fat diet causes insulin resistance is largely unknown. Here, we show that lean mice become insulin resistant after being administered ...exosomes isolated from the feces of obese mice fed a HFD or from patients with type II diabetes. HFD altered the lipid composition of exosomes from predominantly phosphatidylethanolamine (PE) in exosomes from lean animals (L-Exo) to phosphatidylcholine (PC) in exosomes from obese animals (H-Exo). Mechanistically, we show that intestinal H-Exo is taken up by macrophages and hepatocytes, leading to inhibition of the insulin signaling pathway. Moreover, exosome-derived PC binds to and activates AhR, leading to inhibition of the expression of genes essential for activation of the insulin signaling pathway, including IRS-2, and its downstream genes PI3K and Akt. Together, our results reveal HFD-induced exosomes as potential contributors to the development of insulin resistance. Intestinal exosomes thus have potential as broad therapeutic targets.
Purpose
The purpose of this study is to evaluate the effectiveness and safety of liraglutide/liraglutide + metformin in overweight/obese women with polycystic ovary syndrome (PCOS).
Methods
The ...related literatures published until April 2021 were searched in PubMed, Cochrane Library, MEDLINE and EmBase.
Results
Six randomized controlled trials of 127 related articles were obtained through searching. Three articles compared liraglutide with metformin, and four articles compared liraglutide combined with metformin with metformin. Our meta-analysis suggests that liraglutide was superior to metformin only in weight loss MD = − 2.74, 95% CI (− 4.29, − 1.18),
P
= 0.0006. Compared with metformin group, the combination group had significant advantages in weight loss MD = − 3.81, 95% CI (− 5.16, − 2.46),
P
< 0.001, BMI MD = − 2.59, 95% CI (− 3.12, − 2.07),
P
< 0.001, waist circumference MD = − 6.26, 95% CI (− 7.79, − 4.72),
P
< 0.001, fasting blood glucose MD = − 0.59, 95% CI (− 0.74, − 0.44),
P
< 0.001 and fasting insulin MD = − 1.52, 95% CI (− 2.69, − 0.35),
P
= 0.01, while the incidence of adverse reactions was relatively high RR = 2.91, 95% CI (1.55, 5.46),
P
= 0.00009.
Conclusion
The present results indicate that liraglutide and metformin have the similar effects in the treatment of overweight/obese PCOS patients. Liraglutide combined with metformin is more effective than metformin in improving PCOS, but it is necessary to master the correct medication method to reduce the occurrence of adverse reactions.
Most of the state governments in United States (U.S.) issued lockdown or business restrictions amid the COVID-19 pandemic in March 2020, which created a unique opportunity to evaluate the air quality ...response to reduced economic activities. Data acquired from 28 long-term air quality stations across the U.S. revealed widespread but nonuniform reductions of nitrogen dioxide (NO2) and carbon monoxide (CO) during the first phase of lockdown (March 15–April 25, 2020) relative to a pre-lockdown reference period and historical baselines established in 2017–2019. The reductions, up to 49% for NO2 and 37% for CO, are statistically significant at two thirds of the sites and tend to increase with local population density. Significant reductions of particulate matter (PM2.5 and PM10) only occurred in the Northeast and California/Nevada metropolises where NO2 declined the most, while the changes in ozone (O3) were mixed and relatively minor. These findings are consistent with lower transportation and utility demands that dominate NO2 and CO emissions, especially in major urban areas, due to the lockdown. This study provides an insight into potential public health benefits with more aggressive air quality management, which should be factored into strategies to reopen the U.S. and global economy.
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•The lockdown issued due to COVID-19 had nonuniformly impacted air quality in the US.•Consistent NO2 and CO declines corroborate with low transportation/utility demands.•Reductions in NO2 ranged 5–49% and tended to increase with local population density.•Significant PM reductions only occurred where NO2 declined the most.•The impact on O3 was mixed, generally within ±20%.
Background
Resection and strictureplasty are the two surgical modalities used in the management of Crohn’s disease (CD). The objective of this study was to compare morbidity and clinical recurrence ...between patients who underwent strictureplasty and patients who underwent resection.
Methods
Patients with CD who underwent strictureplasty between January 2012 and December 2022 were enrolled. The patients were well matched with patients who underwent resection without strictureplasty. Patient- and disease-specific characteristics, postoperative morbidity, and clinical recurrence were also analyzed.
Results
A total of 118 patients who underwent a total of 192 strictureplasties were well matched to 118 patients who underwent resection. The strictureplasty group exhibited significantly less blood loss (30 ml versus 50 ml,
p
< 0.001) and stoma creation (2.5% versus 16.9%,
p
< 0.001). No significant difference was found regarding postoperative complications or length of postoperative stay. At the end of the follow-up, the overall rate of clinical recurrence was 39.4%, and no difference was observed between the two groups. Postoperative prophylactic use of biologics (odds ratio = 0.2,
p
< 0.001) was the only protective factor against recurrence.
Conclusion
Strictureplasty does not increase the risk of complications or recurrence compared with resection. It represents a viable alternative to resection in selected patients, and as such, it should have a broader scope of indications and greater acceptance among surgeons.
Subsurface microbial communities mediate the transformation and fate of redox sensitive materials including organic matter, metals and radionuclides. Few studies have explored how changing ...geochemical conditions influence the composition of groundwater microbial communities over time. We temporally monitored alterations in abiotic forces on microbial community structure using 1L in-field bioreactors receiving background and contaminated groundwater at the Oak Ridge Reservation, TN. Planktonic and biofilm microbial communities were initialized with background water for 4 days to establish communities in triplicate control reactors and triplicate test reactors and then fed filtered water for 14 days. On day 18, three reactors were switched to receive filtered groundwater from a contaminated well, enriched in total dissolved solids relative to the background site, particularly chloride, nitrate, uranium, and sulfate. Biological and geochemical data were collected throughout the experiment, including planktonic and biofilm DNA for 16S rRNA amplicon sequencing, cell counts, total protein, anions, cations, trace metals, organic acids, bicarbonate, pH, Eh, DO, and conductivity. We observed significant shifts in both planktonic and biofilm microbial communities receiving contaminated water. This included a loss of rare taxa, especially amongst members of the Bacteroidetes, Acidobacteria, Chloroflexi, and Betaproteobacteria, but enrichment in the Fe- and nitrate- reducing Ferribacterium and parasitic Bdellovibrio. These shifted communities were more similar to the contaminated well community, suggesting that geochemical forces substantially influence microbial community diversity and structure. These influences can only be captured through such comprehensive temporal studies, which also enable more robust and accurate predictive models to be developed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Non-pharmaceutical interventions (NPIs) and vaccination are two fundamental approaches for mitigating the coronavirus disease 2019 (COVID-19) pandemic. However, the real-world impact of NPIs versus ...vaccination, or a combination of both, on COVID-19 remains uncertain. To address this, we built a Bayesian inference model to assess the changing effect of NPIs and vaccination on reducing COVID-19 transmission, based on a large-scale dataset including epidemiological parameters, virus variants, vaccines, and climate factors in Europe from August 2020 to October 2021. We found that (1) the combined effect of NPIs and vaccination resulted in a 53% (95% confidence interval: 42-62%) reduction in reproduction number by October 2021, whereas NPIs and vaccination reduced the transmission by 35% and 38%, respectively; (2) compared with vaccination, the change of NPI effect was less sensitive to emerging variants; (3) the relative effect of NPIs declined 12% from May 2021 due to a lower stringency and the introduction of vaccination strategies. Our results demonstrate that NPIs were complementary to vaccination in an effort to reduce COVID-19 transmission, and the relaxation of NPIs might depend on vaccination rates, control targets, and vaccine effectiveness concerning extant and emerging variants.
•First report of NiTi parts created by WAAM using dedicated Ni-rich NiTi wire.•The as-built parts exhibit superelasticity.•The as-deposited material is fully austenitic at room temperature.•Potential ...of using WAAM to deposit advanced functional materials is demonstrated.
Wire and Arc Additive Manufacturing (WAAM) was used for fabrication of NiTi parts using a commercialy available Ni-rich NiTi wire as the feedstock material. The as-built parts are near fully austenitic at room temperature as confirmed by differential scanning calorimetry, X-ray diffraction and superelastic cycling. The as-built microstructure changed from collumnar, in the first deposited layers, to equiaxed in the last deposited ones as a result of the different thermal cycle conditions. This is the first work where WAAM NiTi parts exhibit superelastic behavior under tensile conditions, highlighting the potential use of the technique for the creation of parts shaped in a complex manner based on this material and process. The potential to use WAAM for deposition of advanced functional materials is demonstrated.
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