Background & Aims
Insulin resistance is strongly associated with non‐alcoholic fatty liver disease, a chronic, obesity–related liver disease. Increased endoplasmic reticulum (ER) stress plays an ...important role in the development of insulin resistance. In this study, we investigated the roles of miRNAs in regulating ER stress in the liver of rats with obesity.
Methods
We used miRNA microarray to determine the miRNA expression profiles in the liver of rats fed with a high fat diet (HFD). We used prediction algorithms and luciferase reporter assay to identify the target gene of miRNAs. To overexpress the miRNA miR‐30b or inhibit miR‐30b rats were injected with lentivirus particles containing PGLV3‐miR‐30b or PGLV3‐miR‐30b antimiR through tail vein. Hepatic steatosis was measured using transient elastography in human subjects.
Results
Our data showed that miR‐30b was markedly up‐regulated in the liver of HFD–treated rats. Bioinformatic and in vitro and in vivo studies led us to identify sarco(endo)plasmic reticulum Ca2+‐ATPase 2b (SERCA2b), as a novel target of miR‐30b. Overexpression of miR‐30b induced ER stress and insulin resistance in rats fed with normal diet, whereas inhibition of miR‐30b by miR‐30b antimiR suppressed ER stress and insulin resistance in HFD–treated rats. Finally, our data demonstrated that there was a positive correlation between serum miR‐30b levels and hepatic steatosis or homoeostasis model assessment of insulin resistance (HOMA‐IR) in human subjects.
Conclusions
Our findings suggest that miR‐30b represents not only a potential target for the treatment of insulin resistance, but also a non‐invasive disease biomarker of NAFLD.
This study aimed to investigate the mechanism by which microRNA-206 (miR-206) affects the proliferation, apoptosis, migration and invasion of osteosarcoma (OS) cells by targeting ANXA2 via the AKT ...signaling pathway.
A total of 132 OS tissues and 120 osteochondroma tissues were examined in this study. The targeting relationship between miR-206 and ANXA2 was verified with a dual-luciferase reporter assay. The miR-206 expression and ANXA2, AKT, PARP, FASN, Survivin, Bax, Mcl-1 and Bcl-1 mRNA and protein expression in the above two groups were examined by qRT-PCR and western blotting. The cultured OS cells were divided into 6 groups: a blank group, negative control (NC) group, miR-206 mimic group, miR-206 inhibitor group, si-ANXA2 group and miR-206 inhibitor + si-ANXA2 group. Cell cycle and apoptosis were assessed by flow cytometry, cell migration was examined with a wound-healing assay, and cell invasion was assessed with a Transwell assay. Pearson correlation analysis was used to determine the correlation between ANXA2 mRNA expression and miR-206 expression in OS.
OS tissues exhibited increased mRNA and protein expression of ANXA2, AKT, PARP, FASN, Survivin, Mcl-1 and Bcl-2; decreased miR-206 expression; and decreased Bax mRNA and protein expression. ANXA2 mRNA expression was strongly negatively correlated with miR-206 expression in OS. ANXA2 was found to be a miR-206 target gene. In the miR-206 mimic group and the si-ANXA2 group, the mRNA and protein expression of ANXA2, AKT, PARP, FASN, Survivin, Mcl-1 and Bcl-1 decreased markedly, cell proliferation was inhibited, apoptosis was promoted, higher cell growth in G1 phase and decreased growth in S phase was detected, and decreased cell migration and invasion were observed compared with those in the blank group.
The current results demonstrate that miR-206 overexpression inhibits OS cell proliferation, migration and invasion and promotes apoptosis through targeting ANXA2 by blocking the AKT signaling pathway.
Porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared, loaded with insulin, and then coated in poly(vinyl alcohol) (PVA) and a novel boronic acid-containing copolymer poly(acrylamide ...phenyl boronic acid-co-N-vinylcaprolactam); p(AAPBA-co-NVCL). Multilayer microspheres were generated using a layer-by-layer approach depositing alternating coats of PVA and p(AAPBA-co-NVCL) on the PLGA surface, with the optimal system found to be that with eight alternating layers of each coating. The resultant material comprised spherical particles with a porous PLGA core and the pores covered in the coating layers. Insulin could successfully be loaded into the particles, with loading capacity and encapsulation efficiencies reaching 2.83 ± 0.15 and 82.6 ± 5.1% respectively, and was found to be present in the amorphous form. The insulin-loaded microspheres could regulate drug release in response to a changing concentration of glucose. In vitro and in vivo toxicology tests demonstrated that they are safe and have high biocompatibility. Using the multilayer microspheres to treat diabetic mice, we found they can effectively control blood sugar levels over at least 18 days, retaining their glucose-sensitive properties during this time. Therefore, the novel multilayer microspheres developed in this work have significant potential as smart drug-delivery systems for the treatment of diabetes.
Artificial abnormal microenvironment caused by microperfusion of
l
-glutamate (Glu) and Ca
2+
in the hippocampus results in neuron damage, which is closely related to cerebral ischemia. Ginsenoside ...Rb1, a compound from Panax notoginseng, was previously used to counter the artificial abnormal hippocampal environment in a microperfusion model. In addition, while the Akt/mTOR/PTEN signaling pathway has been shown to mediate neuronprotection in cerebral ischemia, whether this pathway is involved in the neuroprotection of ginsenoside Rb1 is unknown. Here SH-SY5Y cells exposed to OGD/R injury in treated with LY294002, ginsenoside Rb1, ginsenoside Rb1+ LY294002. Expressions of phosphorylation (P-)Akt/P-mTOR/P-PTEN (24 h after OGD/R) were detected by Western blotting. Effects were examined via the memory function of rats (by Morris water maze test), morphological changes in pyramidal cell (by histology), and mRNA expression (by qRT-PCR) and phosphorylation (P-) (by Western blotting and immunohistochemical staining) of Akt, P-mTOR, and P-PTEN in the hippocampus. The memory deficit of rats and pyramidal cellular necrosis and apoptosis in the CA1 region of hippocampus after microperfusion of Glu and Ca
2+
were dose dependently alleviated by ginsenoside Rb1.Moreover,Western blot showed that ginsenoside Rb1 increased the expressions of P-Akt, P-mTOR and reduced P-PTEN in vivo and vitro. Thus, the potent neuroprotection of ginsenoside Rb1 in artificial abnormal microenvironment is, at least partially, related to the activation of P-AKT/P-mTOR signaling pathway and inhibition of P-PTEN protein.
Glucose- and temperature-sensitive polymers of a phenylboronic acid derivative and diethylene glycol dimethacrylate (poly(3-acrylamidophenyl boronic acid-
-diethylene glycol methyl ether ...methacrylate); p(AAPBA-
-DEGMA)) were prepared by reversible addition-fragmentation chain transfer polymerization. Successful polymerization was evidenced by
H nuclear magnetic resonance and infrared spectroscopy, and the polymers were further explored in terms of their glass transition temperatures and by gel permeation chromatography (GPC). The materials were found to be temperature sensitive, with lower critical solution temperatures in the region of 12°C-47°C depending on the monomer ratio used for reaction. The polymers could be self-assembled into nanoparticles (NPs), and the zeta potential and size of these particles were determined as a function of temperature and glucose concentration. Subsequently, the optimum NP formulation was loaded with insulin, and the drug release was studied. We found that insulin was easily encapsulated into the p(AAPBA-
-DEGMA) NPs, with a loading capacity of ~15% and encapsulation efficiency of ~70%. Insulin release could be regulated by changes in temperature and glucose concentration. Furthermore, the NPs were non-toxic both in vitro and in vivo. Finally, the efficacy of the formulations at managing blood glucose levels in a murine hyperglycemic diabetes model was studied. The insulin-loaded NPs could reduce blood glucose levels over an extended period of 48 h. Since they are both temperature and glucose sensitive and offer a sustained-release profile, these systems may comprise potent new formulations for insulin delivery.
Covering crops was a commonly used viticultural technique to adjust the vineyard microclimate, thus affecting the grape and wine quality. In this two-year study, the purslane (Portulaca oleracea L.) ...was used to cover the lands between rows in the vineyards located in the semi-arid Northwest China, Xinjiang. Results showed that the photosynthetically active radiation around the fruit zone and the temperature with the purslane covering treatment decreased. Compared with the clean tillage, covering purslane had lower TSS and higher TA in the grape berries, while lower alcohol content and higher TA was also found in their corresponding wines. Covering purslane treatment significantly increased the contents of anthocyanin and flavonol in the grapes and wines in the year 2018, but no significant effect on flavanols was observed in the wines. Norisoprenoids, esters, and C6 alcohols in the grapes and wines were increased in the purslane covering treatment, respectively. Additionally, compared to the clean tillage, the purslane covering treatment significantly improved the sensory value of the wines, especially the floral aroma and the complexity of the wines. This study helped us to better understand the feasibility of applying covering purslane in viticulture in the semi-arid climate of Northwest China.
•
Distal leaf removal increased the solar radiation of the cluster zone in the first few days after applying LR treatments.
•
Distal leaf removal was beneficial for accumulating C6 alcohols, ...terpenes, and the free form of (
Z
)-
β
-damascenone in grapes.
•
Distal leaf removal significantly increased the fruity and floral intensity of wines because of the increased esters and
β
-damascenone.
•
Whether leaf removal in the same vines over consecutive years or not (1-LRs vs 2-LRs) had limited effects on wines aroma profiles.
The heterogeneity of the vineyard environment caused high variability in grape metabolites and flavor profiles, and the phenomenon was more prominent in recent years of climate change. Herein, distal leaf removal was applied in semi-arid Xinjiang to adjust the source to sink ratio of grapevines for three consecutive years (2018–2020). The grape-derived volatiles showed high correlations with specific climate factors such as temperature changes in the growth period. Results showed that distal leaf removal increased the solar radiation reaching the clusters in the first few days after applying LR treatments while not affecting the temperature. The improvement in fruity and floral aroma intensity by distal leaf removal was founded not only in grape metabolites but also in wines. Moderate cluster exposure brought by distal leaf removal was beneficial for the accumulation of isoprenoids, which therefore increased the fruity and floral intensity of wines. The carry-over effect did not show in consecutively defoliated vines among vintages regarding the wine aroma profile.
Purpose
To perform environmental sampling and molecular identification of
Paragonimus
in endemic regions, which may help in minimizing transmission among humans.
Methods
Mountain crabs from the genus
...Potamiscus
were collected and the encysted metacercariae were extracted and subjected to morphological identification, followed by animal inoculation in Sprague–Dawley (SD) rats. After 112 days of infection, animals were killed and adult worms were extracted from lungs and muscles. The morphology of adult worms was characterized by microscopy and molecular identification was done by polymerase chain reaction, followed by sequencing of
cox1
and
ITS2
genes. Phylogenetic analysis was done by maximum parsimony method.
Results
A total of 447 crabs were captured from the streams of Tongchang Town, Jinping County, Yunnan Province, China. The infection rate was found to be 41% (186 out of 447 crabs). The metacercariae of
Paragonimus skrjabini
was identified by the characteristics round or spherical encysted form measuring 410 to 460 × 400 to 460 µm. After animal infection in SD rats, adults were presumptively confirmed to be
P. skrjabini
, which was also confirmed by gene amplification and sequence analysis of
cox1
and
ITS2
regions.
Paragonimus skrjabini
clustered with previously reported
P. skrjabini
from Yunnan and Vietnam. The confidence values of their branches were > 95%. Phylogenetic analysis of the
ITS2
region revealed two distinct clusters with distinct geographical grouping. Phylogenetic analysis with the combined data sets reiterated the geographical grouping with
P. skrjabini
from Yunnan clustering with strains from Vietnam.
Conclusion
Metacercariae of
P. skrjabini
was discovered in freshwater crabs in Yunnan province, China, and the strains were phylogenetically related to
P. skrjabini
from Vietnam.
•Harvest dates could vary two weeks in adjacent vineyards due to soil variations.•Moderate nutrition in soils produced wines with abundant anthocyanin derivatives.•Harvest ripeness affected wine’s ...flavonoid profiles and color characteristics.•Wine chemical features brought by soils could be resistant to the vintage effect.•The role of anthocyanin derivatives in regulating wine color was clarified.
Recently, revealing the terroir influence on wine chemical features has drawn increasing interest. This study aimed to explain how wine flavonoid signatures were altered by vineyard parcel, harvest ripeness, vintage and bottle aging. Six commercial Cabernet Sauvignon vineyards were selected in the Manas region to produce wines at three harvest ripeness in three seasons (2019–2021) and aged for three years. The six vineyards had little difference in mesoclimate conditions while varying greatly in soil composition. Results showed high vineyard pH (> 8.5) could accelerate grape ripening rate and increase wine flavonol concentration. Vineyards with moderate nutrition produced wines with abundant anthocyanin derivatives and maintained color characteristics during aging. The role of detailed anthocyanin derivatives in regulating wine color was clarified. As the harvest ripeness elevated, wine’s flavonoid profiles were altered and gained a higher red color intensity. This work provides chemical mechanisms underlying single-vineyard wines and a theoretical basis for targeted wine production.
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