Using 17ß-estradiol heparin-poloxamer thermosensitive hydrogel to enhance the endometrial regeneration and functional recovery of intrauterine adhesions in a rat model.

Mechanical damage or infection to the endometrium can lead to the formation of adhesions in the uterine cavity, which may result in reduced reproductive outcome and/or pregnancy complications. The prognosis of this disease is poor due to few effective treatments and the complex environment of endometrium. Heparin-Poloxamer Hydrogel (HP hydrogel) is a nontoxic and biodegradable biomaterial, which has been commonly used as a sustained-release delivery system. In this study, we applied a mini-endometrial curette to scrape the endometrium of rats to mimic the process of curettage in patients. After the establishment of IUA model in rats, we injected the thermo-sensitive hydrogel(E2-HP hydrogel) into the injured uterine cavity and evaluated the therapeutic effect of E2-HP hydrogel on the recovery of IUA. Our results showed that E2-HP hydrogel can significantly facilitate the regeneration of injured endometrium along with inhibiting the cell apoptosis in IUA model. Furthermore, we revealed that E2-HP hydrogel on the recovery of IUA was closely associated with the upregulation of kisspeptin through activating the ERK1/2 and MAPKs p38 pathways. In conclusion, E2-HP hydrogel can effectively transfer E2 into the injured endometrium and it can be considered as a promising therapeutic method for the women with intrauterine adhesions.

Exploiting crosslinked decellularized matrix to achieve uterus regeneration and construction.

Decellularized extracellular matrix (dECM) has been considered as a promising scaffold in xenotransplantation, yet natural tissue dECM is often mechanically weak and rapidly degraded, compromising the outcomes. How to restore the mechanical strength and optimise the in vivo degradation, but maintain the microstructure and maximumly suppress the immune rejection, remains challenging. For this aim, we prepared and characterised various crosslinked decellularized rabbit uterus matrix (dUECM) and evaluated in vivo performance after uterus xenotransplantation from rabbit to rat. Naturally derived genipin (GP) and procyanidins (PC) were chosen to crosslink the dUECM, producing significant mechanical enhanced crosslinked-dUECM along with prolonged enzymatic degradation rate. Xenogeneic subcutaneous graft studies revealed that PC- and GP-crosslinked dUECM experienced significant cell infiltration and caused low immune reactions, indicating the desired biocompatibility. In vivo transplantation of GP- and PC-crosslinked dUECM to a uterus circular excised rat yielded excellent recellularization ability and promoted uterus regeneration after 90 days. While the reconstruction efficacy of crosslinked dUECM is highly depended on the crosslinking degree, crosslinking condition must be carefully evaluated to balance the role of crosslinked dECM in mechanical and biological support for tissue regeneration promotion.

Grazing buffers the effect of climate change on the species diversity of seedlings in an alpine meadow on the Tibetan Plateau.

Climate change predominated by warming over the past decades has affected plant biodiversity, distribution, and ecosystem functioning in alpine grasslands. Yet, little is known about the interactive effect of climate change and grazing on biodiversity and ecosystem functioning. Here, we conducted a vegetation translocation experiment (ten soil-vegetation blocks were translocated from high-altitudinal site 3,245 m to low-altitudinal site 3,045 m) combined with grazing treatment in an alpine meadow on the Tibetan Plateau. The results showed that (a) translocation induced effect of climate change from harsh, high-altitudinal site to benign, low-altitudinal site significantly promoted species richness, and density of asexual and sexual seedling, with an increase in the proportion of asexual recruitment to sexual recruitment; (b) grazing decreased the proportion of asexual seedling to sexual recruitment within community, led to a shift in the dominant plant functional groups from graminoids and legumes to forbs; and (c) grazing partly offset the increased species richness of seedling, but not seedling density, induced by climate change. These findings suggest that moderate grazing may buffer the effect of climate change on the plant community composition, and thus, functional role in alpine meadows. Further understanding the influence of climate change on grassland ecosystems needs to consider the non-additive effect of grazing and climate change to sustainability of grassland services.

Metformin Promotes Regeneration of the Injured Endometrium Via Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis.

Intrauterine adhesion (IUA) is now recognized as one of the most common diseases in reproductive-age women. Metformin, a well-known frontline oral antidiabetic drug, has been found effective in numerous different diseases. The aim of this study was to determine the effect of metformin on reducing adhesions in an animal model of IUA. Sprague-Dawley rats were randomized into 4 groups: sham operation, control, metformin-treated for 7 days, and metformin-treated for 14 days. To establish the IUA model, mechanical injury to the endometria of rats was induced with a mini curette. Metformin was injected intraperitoneally after surgery. A significant amelioration in both the number of glands and the fibrotic area, compared to those of the control group, was detected 14 days after metformin intervention. The expression levels of antigen KI-67 and vascular endothelial growth factor were increased at 7 and 14 days after treatment. However, the transforming growth factor-ß expression was decreased at 14 days after treatment. Endoplasmic reticulum stress-related apoptosis proteins (glucose-regulated protein 78, caspase-12, and CCAAT/enhancer binding protein (EBP) homologous protein) were downregulated after metformin treatment. Moreover, we determined that the effect of metformin was related to the inhibition of endoplasmic reticulum stress-induced apoptosis via the Phosphatidylinositol 3 kinase (PI3K)/Protein kinase B (AKT) and Extracellular regulated protein kinases1/2 pathways. In conclusion, metformin can attenuate the adhesion and promote the regeneration of the endometrium of the IUA rat, and metformin may serve as a novel therapeutic strategy for IUA patients.

[Soil particle size distribution and its fractal dimension among degradation sequences of the alpine meadow in the source region of the Yangtze and Yellow River, Qinghai-Tibetan Plateau, China].

The alpine meadow in the source region of the Yangtze and Yellow River is suffering serious deterioration. Though great efforts have been put into, the restoration for the degraded grassland is far from being effective, mainly due to poor understanding of the degradation mechanism of alpine meadow in this region. In order to clarify the formation mechanism of degradation grassland and provide the new ideas for restoration, degradation sequences of the alpine meadow in the source region of the Yangtze and Yellow River were taken as target systems to analyze the soil particle size distribution, the fractal dimension of the soil particle size, and the relationship between soil erosion modulus and fractal dimension. The results showed that, with increasing grassland degradation, the percentage contents of clay increased while the percentage contents of silt sand and very fine sand showed a decreasing trend. The fractal dimension presented a positive correlation with clay among the degradation sequences while negative correlations were found with very fine sand and silt sand. The curvilinear regression of fractal dimension and erosion modulus fitted a quadratic function. Judged by the function, fractal dimension 2.81 was the threshold value of soil erosion. The threshold value has an indicative meaning on predicting the breakout of grazing-induced erosion and on restoration of the degraded grassland. Taking fractal dimension of 2.81 as the restoration indicator, adoption of corresponding measures to make fractal dimension less than 2.81, would an effective way to restore the degradation grassland.