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Moreover, TAZ was upregulated and accumulated in the nuclei of anti-inflammatory M2-like (M2-L) polarized or myelin-treated microglia. Additionally, XMU-MP-1 (an inhibitor of the Hippo kinase MST1/2 to active TAZ) promoted the aggregation of microglia around the lesion core, resulting in the formation of microglial scars and the functional recovery of mice after SCI. Our findings also indicated that TAZ promoted microglial migration in vitro. Mechanistically, Fascin-1 interacted with TAZ, which upregulated TAZ expression and induced TAZ nuclear accumulation in microglia to promote microglial migration. These findings revealed that TAZ mediated microglial migration to the edge of the lesion core, promoting the formation of microglial scars and functional recovery after SCI. Moreover, TAZ was downstream of Fascin-1, which positively regulated microglial migration after SCI.Nonalcoholic fatty liver disease (NAFLD) is prevalent worldwide, while no pharmaceutical treatment has been approved. Natural herbs are promising for their amelioration effect on lipid metabolism. Theabrownin (TB) and Poria cocos polysaccharide (PCP) have been reported to have effect on hyperlipidemia and diabetes. Here, we compared the effect of individual TB or PCP and the combination of TB and PCP (TB + PCP) on NAFLD phenotypes and the alteration of metabolism in the mice with high-fat diet. The results showed that TB, PCP, and TB + PCP reduced serum and hepatic lipid levels, among which TB + PCP was the most effective. Serum metabolomic profile and liver mRNA analyses revealed that the treatments altered metabolic pathways involved in fatty acid metabolism, bile acid metabolism, and tricarboxylic acid cycle, which was also most significant in the TB + PCP group. This study demonstrated that TB, PCP, especially the combination of TB and PCP could be potential therapeutic formula for NAFLD that promoted lipid utilization and inhibited lipid synthesis and absorption.Background A high prevalence of infantile-onset Pompe disease (IOPD) in the Chinese population has been noted, but there are currently no reported clinical trials of enzyme replacement therapy (ERT) for IOPD in this population. The purpose of this study was to evaluate the efficacy and safety of alglucosidase alfa in Chinese patients with IOPD. Materials and Methods A multicentre, single-arm, prospective, open-label clinical trial was performed at 4 sites in China. Eligible Chinese subjects with IOPD received an infusion of alglucosidase alfa at a dose of 20 mg/kg every 2 weeks for up to 52 weeks. The primary endpoints of clinical efficacy were the survival rate and changes in the left ventricular mass index (LVMI). The safety assessment was based on the incidence of adverse events (AEs). Results A total of 10 eligible subjects were enrolled in the study. The mean age at the start of ERT was 5.36 ± 1.56 months. Nine subjects had survived after 52 weeks of treatment. One subject discontinued the study and died after mechanical ventilation was withdrawn. The intent-to-treat analysis demonstrated that the survival rate was 90.0% (95% confidence interval 55.5-99.7%). The mean LVMI at week 52 was 70.59 ± 39.93 g/m2 compared to that of 298.02 ± 178.43 g/m2 at baseline, with a difference of -227.60 ± 155.99 g/m2. All subjects had left ventricular mass (LVM) Z scores >10 at baseline, and eight subjects (80%) achieved Z scores less then 5 at week 52. No treatment-related AEs were observed, and no AEs led to the discontinuation of treatment. Conclusions This clinical trial is the first study of ERT for IOPD in China, indicating that alglucosidase alfa has favourable efficacy and safety for the treatment of Chinese patients with IOPD (ClinicalTrials.gov number, NCT03687333).Physicians are challenged in treating pain patients due to the lack of quantifiable, objective methods of measuring pain in the clinic; pain sensation is multifaceted and subjective to each individual. There is a critical need for point-of-care quantification of accessible biomarkers to provide objective analyses beyond the subjective pain scales currently employed in clinical care settings. In the present study, we employed an animal model to test the hypothesis that circulating regulators of the inflammatory response directly associate with an objective behavioral response to inflammatory pain. Upon induction of localized paw inflammation, we measured the systemic protein expression of cytokines, and activity levels of matrix metalloproteinases (MMPs) that are known to participate in the inflammatory response at the site of injury and investigated their relationship to the behavioral response across a 24 h period. Intraplantar injection with 1% λ-carrageenan induced a significant increase in paw thickness across this timespan with maximal effects observed at the 8 h timepoint when locomotor activity was also impaired. Expression of the chemokines C-X-C motif chemokine ligand 1 (CXCL1) and C-C motif chemokine ligand 2 (CCL2) positively correlated with paw inflammation and negatively correlated with locomotor activity at 8 h. The ratio of MMP9 to MMP2 activity negatively correlated with paw inflammation at the 8 h timepoint. We postulate that the CXCL1 and CCL2 as well as the ratio of MMP9 to MMP2 activity may serve as predictive biomarkers for the timecourse of inflammation-associated locomotor impairment. These data define opportunities for the future development of a point-of-care device to objectively quantify biomarkers for inflammatory pain states.Coronaviruses have been at the forefront of the news for the last 2 years. Unfortunately, SARS-CoV-2, the etiologic agent for the COVID-19 pandemic, must be manipulated in biosecurity level 3 settings, which significantly limits research. Meanwhile, several less pathogenic human coronaviruses (HCoV) exist and can be studied in much more common biosafety level 2 laboratories. Among them, HCoV-OC43 is a good surrogate candidate for SARS-CoV-2 since both are phylogenetically related human Betacoronaviruses. However, one issue has been the lack of standardized means among laboratories to propagate and titer this less virulent coronavirus. The present study probes the optimal parameters to propagate HCoV-OC43. First, testing of five different cell lines (MRC-5, Huh7.5, Vero, HCT-8, HRT-18) indicated that the physiologically relevant MRC-5 human lung cell line produced among the highest viral titers. HRT-18 may however be an interesting alternative as they are quick growing cells that also led to higher viral titere HRT-18 cells appeared more sensitive to quantify the virus. Perhaps most importantly, these optimized protocols routinely led to high titer viral stocks in the order of 108 TCID50/ml magnitude, which should fulfill the requirements of most experimental settings.Restoration is the natural and intervention-assisted set of processes designed to promote and facilitate the recovery of an ecosystem that has been degraded, damaged, or destroyed. However, it can also have an adverse effect on the environment. Thus, assessing an ecological restoration project's impact is crucial to determining its success and optimum management strategies. We performed a meta-analysis concerning the environmental outcomes during the years 2000-2015 resulting from the "Grain for Green" Project (GFGP) implementation in the Loess Plateau (LP). Data were gathered from 40 peer-reviewed English-language articles chosen from a pool of 332 articles. The results showed that, on average, GFGP increased forest coverage by 35.7% (95% CI [24.15-47.52%]), and grassland by 1.05% (95% CI [0.8-1.28%]). At the same time, GFGP has a positive impact on soil carbon (C) sequestration, net ecosystem production (NEP), and net primary production (NPP), from the years 2000 to 2015 by an average of 36% (95% CI [28.96-43.18%]), 22.7% (95% CI [9.10-36.79%]), and 13.5% (95% CI [9.44-17.354%]), respectively. Soil erosion, sediment load, runoff coefficient, and water yield were reduced by 13.3% (95% CI [0.27-25.76%]), 21.5% (95% CI [1.50-39.99%]), 22.4% (95% CI [5.28-40.45%]) and 43.3% (95% CI [27.03-82.86%]), respectively, from the years 2000 to 2015. Our results indicate that water supply decreased with the increase of vegetation coverage. Therefore, to balance the needs for green space, GFGP policies and strategies should recover, enhance, and sustain more resilient ecosystems.Microsporidia are obligate intracellular parasites that can infect a wide range of vertebrates and invertebrates including humans and insects, such as silkworm and bees. The microsporidium Nosema bombycis can cause pebrine in Bombyx mori, which is the most destructive disease in the sericulture industry. Although membrane proteins are involved in a wide range of cellular functions and part of many important metabolic pathways, there are rare reports about the membrane proteins of microsporidia up to now. We screened a putative membrane protein Ycf 1 from the midgut transcriptome of the N. bombycis-infected silkworm. Gene cloning and bioinformatics analysis showed that the Ycf 1 gene contains a complete open reading frame (ORF) of 969 bp in length encoding a 322 amino acid polypeptide that has one signal peptide and one transmembrane domain. Indirect immunofluorescence results showed that Ycf 1 protein is distributed on the plasma membrane. Expression pattern analysis showed that the Ycf 1 gene expressed in all developmental stages of N. selleck chemical bombycis. Knockdown of the Ycf 1 gene by RNAi effectively inhibited the proliferation of N. bombycis. These results indicated that Ycf 1 is a membrane protein and plays an important role in the life cycle of N. bombycis.
Iodine is a vital mineral of the human body that acts by maintaining the health of the thyroid gland. Research has shown that iodine-rich food allergy (
., seafood allergy) is not caused by iodine itself; instead, it is caused by other proteins including tropomyosin and parvalbumin in shellfish and fish, respectively. Amiodarone is a commonly used antiarrhythmic agent containing a significant amount of iodine.
This study's objective was to assess pharmacists' knowledge, attitude, and practices toward the misconception of iodine allergy and the cross-reactivity with amiodarone.
In February 2020, a cross-sectional study was conducted by sending out an online survey to three pharmaceutical organizations (Saudi Pharmaceutical Society, Kuwait Pharmaceutical Association, and Oman Pharmaceutical Society). Additionally, an electronic questionnaire was administered to pharmacists attending the Dubai International Pharmaceuticals and Technologies Conference and Exhibition 2020 (DUPHAT). Chi-square or Fisher's exrning iodine allergy and cross-reactivity with amiodarone was evident. Implementation of educational programs targeting pharmacists is necessary to correct these misconceptions.
Pharmacists' misconception concerning iodine allergy and cross-reactivity with amiodarone was evident. Implementation of educational programs targeting pharmacists is necessary to correct these misconceptions.
The gastrointestinal (GI) bacterial communities of sea lions described to date have occasionally revealed large intraspecific variability, which may originate from several factors including different methodological approaches. Indeed, GI bacterial community surveys commonly rely on the use of a single hypervariable region (HR) of
, which may result in misleading structural interpretations and limit comparisons among studies. Here, we considered a multi-locus analysis by targeting six HRs of
with the aims of (i) comprehensively assessing the GI bacterial consortium in rectal samples from
pups and (ii) elucidating structural variations among the tested HRs. In addition, we evaluated which HRs may be most suitable for identifying intrinsic, structurally related microbiome characteristics, such as geographic variations or functional capabilities.
We employed a Short MUltiple Regions Framework (SMURF) approach using the Ion 16S™ Metagenomic Kit. This kit provides different proprietary primers designed to target six HRs of the
gene.