The aim of the present study was to investigate the potential mechanism of retinopathy of prematurity (ROP) using an oxygen-induced retinopathy (OIR) mouse model. For experiments, mice were divided into either the OIR group or control group. Fluorescein isothiocyanate-dextran cardiac perfusion and stretched retina preparation were performed. The total retina area, area of instillation, density of microvascular network, area of new blood vessels, vein width and the tortuosity of arteries were measured. Next, mice were randomly assigned into the PBS, soluble TEK receptor tyrosine kinase (sTie2)-fusion protein (Fc), angiopoietin 1 (Ang1), ranibizumab, ranibizumab + sTie2-Fc and ranibizumab + Ang1 treatment groups. Following housing for 5 days, the body weight of each mouse was recorded. Mice in the OIR group presented smaller total retina area and larger area of instillation, larger area of new blood vessels, and higher microvascular network density compared with the control PBS group. Obvious retinal vein dilatation and arterial tortuosity were identified in the OIR group. The amount of endotheliocyte nuclei of new vessels beyond the inner limiting membrane was larger in the OIR group compared with the control group. Furthermore in the next set of experiments, a larger area of instillation, smaller area of new blood vessels and decreased amount of endotheliocyte nuclei of new vessels were observed in the sTie2-Fc group, Ang1 group, ranibizumab group, ranibizumab + sTie2-Fc group and ranibizumab + Ang1 group compared with the PBS group. Specifically, the ranibizumab + sTie2-Fc group and ranibizumab + Ang1 group demonstrated markedly reduced retina instillation area and microvascular network density in the instillation area. Total retina area and body weight following 10 days of the experiment for the ranibizumab group were significantly lower compared with other groups. In conclusion, the combined regulation of the Ang/Tie2 and the vascular endothelial growth factor (VEGF)/VEGF receptor pathways markedly increased the efficacy of treatment with retinal neovascularization (RNV). Regulation of these pathways has a potential for treating RNV, in particular ROP.

Intrauterine adhesion (IUA) is a disease characterized by endometrial fibrosis caused by injury to the endometrium. In the present study, decellularized and lyophilized human amniotic membrane (DL-AM) material was transplanted in a rat model to explore the preventive effect against IUA. A total of 24 Sprague Dawley rats were randomly divided into an IUA (n=12) group and an IUA + DL-AM (n=12) group. To establish the model, the endometrium of the left uterus was scraped, while that of the right uterus was used as a control. In the IUA group, scraped uteri were sutured without any other treatment, whereas DL-AM was transplanted onto the scraped uteri in the IUA + DL-AM group. Uteri were resected for histological and immunohistochemical evaluation at 3, 7, 14 and 28 days after surgery. The results confirmed the development of IUA, which was accompanied by an increase in the rate of fibrotic area. Integral optical density (IOD) values of connective tissue growth factor (CTGF) were elevated in the IUA group, while matrix metalloproteinase-2 (MMP-2) decreased relative to the control group (P<0.05). After DL-AM transplantation, the IOD value of CTGF dropped, while MMP-2 increased compared with the IUA group (P<0.05). However, compared with that in the control group, the IOD value of CTGF was still higher, whereas MMP-2 was still lower in the IUA + DL-AM group (P<0.05). Furthermore, no evidence of endometrial regeneration was detected in both the IUA and IUA + DL-AM groups. Overall, these results indicated that in the rat model of IUA, transplantation of DL-AM had the potential to prevent the formation of fibrosis to a certain extent and may thus be an alternative strategy for managing the condition.

Statins are HMG-CoA reductase inhibitors that are used to decrease the blood levels of low-density lipoprotein (LDL). In addition, they have been shown to exert pleiotropic protective effects in the absence of LDL-lowering activity. The present study investigated the effects of lovastatin on global gene expression in human umbilical vein endothelial cells (HUVECs), in order to further explore its ability to protect against oxidized (ox)-LDL-induced cytotoxicity. HUVECs were treated with lovastatin for 2-24 h, and gene expression patterns were analyzed using cDNA microarrays. The results suggested that numerous genes were regulated by lovastatin, including certain genes associated with cell survival, such as PTK2B, BCL2 and MAP3K3. In particular, PTK2B, which has been shown to exert anti-apoptotic effects against ox-LDL-induced cell injury, was upregulated by lovastatin. Knockdown of PTK2B was able to attenuate ox-LDL-induced cell injury, and this was associated with decreased levels of phosphorylated-AKT and eNOS, and inhibition of mitochondrial-dependent apoptosis. In conclusion, the results of the present study suggested that lovastatin protects against ox-LDL-induced cell injury, potentially via the upregulation of PTK2B, which regulates the anti-apoptosis signaling pathway.

Sinomenine is a pure alkaloid that can be isolated from the root of Sinomenium acutum and has been found to exert anti-inflammatory and immunosuppressive effects. The present study investigated the effects of sinomenine hydrochloride (SIN) on inflammation and the gut microbiota composition in the colon of mouse models of dextran sulfate sodium (DSS)-induced colitis. DSS-induced mice colitis was established by treating the mice with drinking water containing 3% (w/v) DSS for 7 days. The disease activity index of each mouse was calculated on a daily basis. All mice were sacrificed on day 11, then the weight of their spleen and length of their colons were measured. The histological analysis was measured by hematoxylin-eosin staining. Oral administration of SIN (100 mg/kg/day) attenuated the DSS-induced increases in the disease activity indices and spleen indices, DSS-induced shortening of the colon length and histological damage. In addition, reverse transcription-quantitative PCR data showed that SIN treatment effectively regulated the expression of inflammatory mediators, specifically by suppressing the expression of proinflammatory gene (TNF-α, IL-6 and inducible nitric oxide synthase) whilst increasing those associated with inhibiting inflammation (IL-10 and arginine 1). Gut microbiota analysis was conducted using 16S ribosomal DNA sequencing. The results revealed that SIN improved bacterial community homeostasis and diversity, which were damaged by DSS. Furthermore, western blotting showed that the activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome was markedly suppressed by SIN treatment. In conclusion, these results indicated that SIN may ameliorate experimental colitis by modulating the gut microbiota composition and suppressing the activation of the NLRP3 inflammasome in mice. Overall, these findings suggested a broad protective effect of SIN in treating inflammatory gut diseases, including ulcerative colitis.

Butyrate is one of the most abundant short-chain fatty acids produced by intestinal bacteria. In the present study, the action of butyrate on chronic gastric mucosa lesions was investigated, as well as its underlying mechanism in mice. Male mice from the Institute of Cancer Research were randomly divided into three groups: Sham, model and butyrate groups. Butyrate was administered intragastrically for 7 days to butyrate group mice following the establishment of a gastric ulcer model. Hematoxylin and eosin staining, immunohistochemical analysis, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction were used to determine the therapeutic effects and molecular mechanism of butyrate treatment. The findings demonstrated that butyrate induced a marked shift in superoxide dismutase and catalase activities, along with a decrease in malondialdehyde levels, thereby attenuating oxidative stress. Furthermore, butyrate decreased the levels of pro-inflammatory cytokines interleukin-1β, tumour necrosis factor-α and leukotriene B4, which helped combat inflammatory responses. Moreover, butyrate treatment exerted remarkable positive influences that mediate an increase in 6-keto-PGF-1α (a degradation product of prostacyclin), trefoil factor 2, MUC5AC and fibroblast growth factor-7 levels to promote gastric mucosal repair. The expression of specific receptor GPR109A for butyrate was upregulated, with no significant difference noted in the expression of GPR43 or GPR41. Overall, the present findings revealed that butyrate exerted therapeutic effects by upregulating mucosal repair factors and stimulating protective responses against oxidation and inflammation. GPR109A may be the key receptor for butyrate therapy.

The aim of the present study was to investigate the anti-hepatitis B virus (HBV) effect of interferon (IFN)-thymosin α1 (TA1) in a transgenic Dunaliella salina (TDS) system in vitro and in vivo. The toxicity of TDS in the HepG2.2.15 cell line was assessed using an MTT assay. The effect of TDS on the secretion of HBV early antigen (HBeAg) and HBV surface antigen (HBsAg) in culture supernatants was measured using ELISA. In addition, HBV-DNA was analyzed using quantitative polymerase chain reaction. Drug treatment experiments were performed in vivo on ducks congenitally infected with duck HBV (DHBV). The drug was administered once daily for 21 continuous days. Blood was drawn from all ducks prior to treatment, following treatment for 7, 14 and 21 days, and following drug withdrawal for 5 days. Serum DHBV-DNA was determined using quantitative PCR. In addition, the histology of duck liver tissues was assessed using hematoxylin and eosin, and orcein staining. The results demonstrated that TDS suppressed cell viability and HBsAg and HBeAg secretion in HepG2.2.15 cells. Furthermore, the treatment index values for HBsAg and HBeAg following TDS treatment were 2.96 and 3.07 respectively, which were greater than those of the IFN-α treated group. In addition, the DHBV-infected duck model experiments indicated that serum DHBV-DNA levels were significantly decreased in the group of TDS (20 g/kg) following treatment for 7, 14 and 21 days compared with the control group. Following withdrawal of the drug for 5 days, the levels of DHBV-DNA did not relapse in the medium and high dose groups of TDS (10 and 20 g/kg, respectively). Histological analysis of duck liver also demonstrated that TDS and IFN-α treatment alleviated inflammation and HBsAg signals in duck livers. In conclusion, TDS markedly suppresses HBV replication in vitro and in vivo and its anti-HBV effect is greater than that of IFN-α.

Myocardial injury is an indicator of poor prognosis in sepsis, whereas propofol has been reported to protect the myocardium. Therefore, the present study investigated the effect of propofol on myocardial injury in sepsis and its mechanism. An in vitro model of myocardial cell injury was established in myocardial H9C2 cells using lipopolysaccharide (LPS). The Cell Counting Kit 8 (CCK8) assay was used to investigate the effect of propofol pretreatment on the viability of normal and LPS-challenged H9C2 cells, whereas the lactate dehydrogenase (LDH) detection kit was used to measure the levels of LDH. The expression levels of LC3 were analyzed using an immunofluorescence assay. Western blotting was performed to analyze the expression levels of autophagy-related proteins. Following treatment with the autophagy inhibitor 3-methyladenine, CCK8 assay, TUNEL assay, western blotting, 2,7-dichlorohydrofluorescein diacetate assay and ELISA were performed to investigate whether propofol exerted its effects on cell viability, apoptosis, oxidative stress and inflammation via autophagy. Moreover, to further explore the regulatory mechanism of propofol in myocardial injury, sirtuin 1 (SIRT1) was knocked down via transfection with small interfering RNA, and SIRT1 protein was inhibited via the addition of the SIRT1 inhibitor EX527. The present study demonstrated that propofol activated autophagy in LPS-induced cardiomyocytes, and reversed the effects of LPS on viability, apoptosis, oxidative stress and the inflammatory response. Moreover, SIRT1 knockdown and inhibition decreased the activation of autophagy and the protective effect of propofol on LPS-induced cardiomyocytes. In conclusion, propofol reduced LPS-induced cardiomyocyte injury by activating SIRT1-mediated autophagy.

Resibufogenin (RBG) is an active ingredient of toad venom that also has antitumor potential. The present study aimed to investigate the role of RBG in multiple myeloma (MM) and the underlying action mechanism involving the PI3K/Akt signaling pathway. A human MM cell line, RPMI8226, was treated with RBG and/or insulin-like growth factor 1 (IGF-1; an activator of the PI3K/AKT signaling pathway). Cell viability and apoptosis were detected using Cell Counting Kit-8 and flow cytometry, respectively. Cell migration and invasion were detected using a Transwell assay. In addition, the epithelial-mesenchymal transition (EMT)-associated proteins (E-cadherin, N-cadherin and Vimentin) and the PI3K/AKT pathway-associated proteins [AKT, phosphorylated (p)-AKT, PI3K and p-PI3K] were measured using western blotting. RBG inhibited the viability, migration and invasion, and promoted the apoptosis of RPMI8226 cells in a dose-dependent manner. RBG at concentrations of 4 and 8 µM upregulated E-cadherin, and downregulated N-cadherin and Vimentin in RPMI8226 cells. RBG also decreased the protein expression of p-AKT and p-PI3K in a dose-dependent manner. In addition, the intervention of IGF-1 weakened the inhibitory effects of RBG on the malignant characteristics of MM cells. RBG-induced inhibition of EMT and the PI3K/AKT pathway were also weakened by IGF-1 treatment. In conclusion, RBG inhibited viability, migration, invasion and EMT, and promoted the apoptosis of MM cells by blocking the PI3K/AKT signaling pathway.