Objective To investigate the changes of expression of peroxisome proliferator-activated receptor γ (PPARγ) and its coregulators and monocyte chemotactic factor (MCP-1) treated with intedeukin-1β (IL-1β), and to analyze the mechanism of interaction of these factors. Methods Renal tubular cells (HK-2 cells) were cultured in vitro. Total cellular RNA was isolated for real-lime quantitative polymerase chain reaction (real-time PCR), nuclear extracts were prepared for Western blot analysis and EMSA. The supernatant was collected for ELISA after the treatment of IL-1β at different concentrations and time points. Results Under stimulus of different concentrations of IL-1β (0～20 μg/L) for 24 hours, the mRNA expression of PPARγ, SRC-1, SRC-2 and PGC-1 decreased significantly (P<0.05), meanwhile NCoR increased obviously (P<0.05). In further time-dependent experiment, the mRNA levels of SRC-2 and PGC-1 decreased by 57% and 48%, respectively, at 1 hour after treatment with 10 μg/L IL-1β (P<0.05). The expression of SRC-1 decreased by 43%only after 2 hours (P<0.05). The expression of NCoR was not obviously changed until stimulated by IL-1β for 8 hours (2.17 folds, P<0.05), then it decreased slowly. In the same time-dependent experiment, Western blot analysis showed that IL-1β (10 μg/L) significantly decreased the protein level of PPARγ at 4 hours (P<0.05). ELISA analysis revealed that the secretion of MCP-1 kept on rising and reached the peak (160.56±2.80) ng/L at 8 hours (P<0.01), then decreased to (50.82±1.25) ng/L at 24 hours (P<0.01). IL-1β could down-regulate the DNA binding activity of PPARγ, and the activity of NF-κB was up-regulated. Conclusions PPARγ and its eoregulators are closely related to MCP-1 and NF-κB during inflammation response in kidney. The activation of NF-κB by IL-1β leads to the decrease of PPARγ, and its coactivators expression levels, however the expression of MCP-1 and NCoR in renal tubular epithelial cells is up-regulated. PPARγ together with its coregulators participate in the inflammation response in kidney.

ObjectiveTo investigate the role of MG-132, a specific dipeptide proteasome inhibitor, on the proliferation, apoptosis and the related proteins in renal interstitial fibroblasts. MethodsRenal interstitial fibroblasts (NRK-49F) were induced by transforming growth factor β1 (TGF-β1, 5 μg/L) and pro-treated with MG-132 (0～5 μmol/L). The cell proliferation was measured with MTT method. Cell cycle and apoptosis were analyzed by flow cytometry. The apoptosis was also analyzed by Annexin V/PI staining and DNA ladder. Expression of p53, p27, p21, caspase-3, Bcl-2 and Bax protein was examined by Western blot. ResultsTGF-β1 (5 μg/L) could stimulate the proliferation of NRK-49F. MG-132 (0.25～5 μmol/L) could inhibit TGF-β1-induced proliferation in a dose-dependent manner through G1-arrest. TGF-β1 alone could not induce apoptosis (3.880%±0.365% vs 4.723%±1.582%). But pretreatment of MG-132 (0.1～2.5 μmol/L) could significantly induce apoptosis of TGF-β1-stimulated NRK-49F in a dose-dependent manner. Typical DNA ladder was also confirmed in these two groups in the DNA fragments analysis after being incubated with 2.5 μmol/L MG-132 with or without 5 μg/L TGF-β1. Western blot showed that MG-132 could activate the cell-cycle and apoptosis-related proteins such as p53, p21, caspase-3, Bax and inhibit Bcl-2 in a dose-dependent manner, while expression of p27 remained unchanged. ConclusionsProteasome inhibitor MG-132 can inhibit proliferation and induce the cell apoptosis in renal interstitial fibroblasts stimulated by TGF-β1. The mechanism may be associated to the mediation of p53, p21, caspase-3, Bcl-2 and bax pathways. Protoasome inhibitor may be a new strategy to treat renal interstitial fibrosis.

BACKGROUND:The key to preventing the recurrence of intrauterine adhesions is to reconstruct the endometrium with normal function.The latest breakthrough in the treatment of recurrent intrauterine adhesions in and outside China is the use of degradable materials to prepare hydrogels to prevent the recurrence of adhesions. OBJECTIVE:To review the research advance in hydrogel-promoted endometrial repair in intrauterine adhesions. METHODS:PubMed,Web of Science,China National Knowledge Infrastructure(CNKI),and WanFang databases were searched systematically,with the keywords"intrauterine adhesions,endometrial injury,endometrium regeneration,hydrogel"in Chinese and English.Relevant articles published in each database from January 1990 to March 2023 were collected. RESULTS AND CONCLUSION:In recent years,research on hydrogel-promoted endometrial repair in uterine adhesions in and outside China has made some progress and plays an important role in the prevention and treatment of intrauterine adhesions and the promotion of endometrial repair:(1)As an important carrier in tissue engineering,hydrogel itself has excellent biocompatibility,biodegradability and three-dimensional network structure,which can be better applied in the treatment of intrauterine adhesions.(2)The hydrogel-based carrier system can promote the proliferation and differentiation of endometrial epithelial cells by transporting drugs/biologics/stem cells,and restore normal uterine morphology to prevent adhesion recurrence.(3)Hyaluronic acid hydrogels can not only meet good biocompatibility,but also promote the proliferation and differentiation of endometrial epithelial cells,and will be hydrolyzed by corresponding enzymes in utero,without affecting the normal metabolism of the body.They are currently commonly used uterine anti-adhesion agents in the clinic and are also the most commonly used hydrogel carriers in tissue engineering research.(4)Poloxamer hydrogel with excellent temperature-sensitive properties can rapidly gelate into the body,quickly form a physical barrier,and can play a slow-release effect on carrying substances and provide a platform for cell growth/adhesion.(5)There are broad prospects for the preparation of therapeutic hydrogels using materials with different characteristics,such as temperature-sensitive hydrogels,pH-responsive hydrogels and photosensitive hydrogels,but there are still many problems to be solved,such as the safety of the hydrogel system,whether the degradation products cause immune reactions,and whether they have an impact on the normal body's menstrual period.A large number of animal experiments and clinical trials are needed to verify its safety and efficacy,and continuously improve the treatment strategy.

Objective: To investigate the antibacterial properties and the osteoblast-compatibility of chlorhexidine (CHX)-modified porous titanium. Methods: Smooth pure titanium specimen with diameter of 10.0 mm and thickness of 1.5 mm treated with alkali heat method were set as control group. Those with covalent conjugation of aminosilane were set as silane group, and those with CHX grafted by glutaraldehyde were set as CHX group. Scanning electron microscope (SEM) was used to observe the surface morphology and element compositions were detected by X-ray photoelectron spectroscopy. Hydrophilicity was analyzed by surface water contact angle test (n=6), while surface amino/imine groups quantification were performed through acid orangeⅡ(n=5) and the CHX was quantified by optical densitometric method (n=5). Live/dead bacterial staining, the morphology of adherent bacteria by SEM, plate counting method and inhibition zone method were executed to evaluate the antibacterial property of the samples. Osteoblast compatibility was evaluated by methyl thiazolyl tetrazolium. Cell-bacterial co-culture was conducted to evaluated the cell viability on the samples under the circumstance with bacteria. Results: After CHX grafting, pores on the titanium surface were decreased, while the atom ratio of C, N, Cl increased and the water contact angle decreased to 37.5°±4.0°. The density of CHX on the surface was (5.07±0.39) μg/cm². The results of live/dead bacterial staining and the morphology of adherent bacteria showed that only little dead bacterial (bacterial wall rupture) adherent on the surface of CHX group, which proved that the modified surface could inhibit bacteria adhesion and even destroyed bacteria; the plate counting displayed sporadic colonies and a transparent inhibition zone could be observed, which demonstrated that CHX group could suppress bacteria multiplication from surrounding environment. When incubating for 1 and 3 days, the cell viability of CHX group showed no significant difference from that of control group (P>0.05) ; when incubating for 5 days, the value of cell viability of CHX group was 0.547±0.087, and this was significantly lower than that of the control group (0.751±0.056) (P<0.05), demonstrating a slight inhibition of cell proliferation by CHX. The results of bacteria-cell co-culture for 3 days showed that a mass of bacteria adhered on the surface of the control group while considerable cells adhered on the surface of CHX group and exhibited a good shape. Conclusions Porous titanium surface grafted by CHX showed an excellent antibacterial properties and allowed cell adhesion in bacterial circumstance, providing immediate implantation options for patients with bad oral health.

Thyroid hormones are crucial for energy metabolism. Thyroid dysfunction is closely related to a variety of metabolic disorders. However, evaluation relying solely on thyroid function indicators may come up short, considering the complex relationship between thyroid hormones and metabolic issues. There has been a growing recognition of sensitivity to thyroid hormones as a measure of thyroid function complementary to traditional indices. The indicators of thyroid hormone sensitivity include free triiodothyronine/free thyroxine, thyrotroph thyroxine resistance index, thyroid-stimulating hormone index and thyroid feedback quantile-cased index. It has been reported that impaired sensitivity to thyroid hormones can potentially interact with various nutritional imbalances and metabolic abnormalities, such as metabolic syndrome, osteoporosis and decreased vitamin D, which are not only of concern to those with thyroid dysfunction, but also to euthyroid individuals in terms of prevention and prophylaxis. With the aim of providing comprehensive insights, this review is intended to systematically summarize the existing evidence on the association between sensitivity to thyroid hormones and metabolic disorders.