Glycyrrhizic acid attenuates the malignant biological properties of nonalcoholic fatty liver disease-related hepatocellular carcinoma.

Glycyrrhizic acid (GA) has effects on anti-hepatic fibrosis, anti-tumor and prevention from hepatocellular carcinoma (HCC) progression. Yet, the capacity of GA to ameliorate the advance of HCC pertinent to nonalcoholic fatty liver disease (NAFLD) remains to be clarified. We used the CCK-8 method to detect the optimal treatment concentration and time for L-02 cells, palmitic acid (PA)-induced L-02 cells and HepG2 cells, and selected 40 µM and 48 h to treat PA-induced L-02 cells and 60 µM for 24 h to treat HepG2 cells. Moreover, functional associations of HepG2 cells were elucidated through various assays. The results showed that GA demonstrated enhances lipid deposition and alleviates the inflammatory response in L-02 cells induced by palmitic acid. Simultaneously, we found that GA inhibits the proliferation, migration, and invasion while promoting apoptosis in HepG2 cells. In pursuit of constructing of HCC model rats, a combination of high-fat diets and diethylnitrosamine was utilized. The results showed that GA significantly decreased the liver index, body weight, liver weight, and the number of nodules in HCC model rats. Moreover, GA mitigated infiltration and heightened apoptosis in these rats. Mechanistically, GA notably attenuated the KKß/NF-κB pathway in both HepG2 cells and the HCC model rats. In conclusion, GA functions as an inhibitor in the progression of NAFLD-related HCC cells, which might be relevant to the KKß/NF-κB pathway. Therefore, GA is a potential drug for NAFLD-related HCC treatment.

Astragaloside IV induces the protective effect of bone marrow mesenchymal stem cells derived exosomes in acute myocardial infarction by inducing angiogenesis and inhibiting apoptosis.

Bone marrow mesenchymal stem cells (BMECs)-derived exosomes (MSC-Exo) can improve acute myocardial infarction (AMI). Astragaloside IV (AS-IV) has also been reported to have cardioprotective pharmacological effects. However, it is not entirely clear whether AS-IV can improve AMI by inducing MSC-Exo. BMSCs and MSC-Exo were isolated and identified, and we also established the AMI rat model and the OGD/R model with H9c2 cells. After MSC-Exo or AS-IV-mediated MSC-Exo treatment, cell angiogenesis, migration, and apoptosis were evaluated by tube formation, wound healing, and TUNEL staining. The cardiac function of the rats was measured by echocardiography. The pathological changes and collagen deposition in rats were also assessed with Masson and Sirius red staining. The levels of α-SMA, CD31 and inflammatory factors were determined by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). In vitro, AS-IV-mediated MSC-Exo can significantly enhance the angiogenesis and migration of H9c2 cells induced by OGD/R, and significantly reduce their apoptosis. In vivo, AS-IV-mediated MSC-Exo can improve the cardiac function of rats, and attenuate pathological damage and collagen deposition in AMI model rats. In addition, AS-IV-mediated MSC-Exo can also promote angiogenesis and reduce inflammatory factors in rats with AMI. AS-IV-stimulated MSC-Exo can improve myocardial contractile function, myocardial fibrosis and angiogenesis, reduce inflammatory factors and induce apoptosis in rats after AMI.

Computation of transverse-electric polarized optical eigenstates in dielectric systems based on perfectly matched layer.

The optical resonance problem is an eigenproblem with an exponential-growing boundary condition imposed at infinity. This inconvenient boundary condition is caused by the openness of dielectric systems, and it is explained as the effect of retardation. Following our previous work [Jiang and Xiang, Phys. Rev. A 102, 053704 (2020)2469-992610.1103/PhysRevA.102.053704] where a perfectly-matched-layer method is developed for transverse-magnetic modes, we extend the method in this paper to transverse-electric modes and apply it to study mode symmetries. The method is implemented by introducing an extra layer to absorb outgoing waves at the far-field region, based on which we derive a damping eigenequation. A finite-element-based numerical approach is developed to compute the eigenstates of the damping eigenproblem. Our method is validated by application to the circular cavity and comparison with exact analytical solutions of whispering-gallery modes. We apply the method to the elliptic cavity to study the even- and odd-symmetric optical eigenstates. We also apply the method to trace the evolution of a pair of degenerate eigenstates with cavity shapes smoothly deformed from circles to squares.

Regulatory Mechanism miR-302a-3p/E2F1/SNHG3 Axis in Nerve Repair Post Cerebral Ischemic Stroke.

OBJECTIVE: Cerebral ischemic stroke (CIS) remains a primary cause of death worldwide. The current knowledge has identified the implication of microRNAs (miRNAs) in the pathophysiology of CIS. This study investigated the mechanism of miR-302a-3p in nerve repair post CIS. METHODS: A middle cerebral artery occlusion (MCAO) model was established in mice to simulate CIS. miR-302a-3p expression in brain tissues of MCAO mice was up-regulated by injecting agomiR-302a-3p. Neurological deficits of MCAO mice were evaluated through neurological function score, forelimb placing test, and balance beam walking test. Neuronal damage was measured using Nissl staining. The concentrations of nerve injury-related factors (S100B and GFAP) and the contents of neuroinflammatory factors (TNF-α and IL-1ß) in serum were examined using ELISA kits. miR-302a-3p, E2F1, and long non-coding RNA (lncRNA) SNHG3 expressions in brain tissues of MCAO mice were determined using RT-qPCR and Western blot. The binding relationships between miR-302a-3p and E2F1 and E2F1 and SNHG3 were validated using dual-luciferase and ChIP assays, respectively. RESULTS: miR-302a-3p expression was reduced in brain tissues of MCAO mice. miR-302a-3p overexpression increased the number of neurons, decreased the concentrations of S100B and GFAP, reduced the contents of TNF-α and IL-1ß, promoted nerve repair, and alleviated CIS-induced brain injury. miR-302a-3p targeted E2F1 expression, and E2F1 activated SNHG3 transcription. E2F1 overexpression or SNHG3 overexpression reversed the effect of miR-302a-3p overexpression on nerve repair in MCAO mice. CONCLUSION: miR-302a-3p overexpression repressed SNHG3 transcription by targeting E2F1 expression, thereby promoting nerve repair and alleviating CIS.

Malic enzyme 2 promotes the progression of hepatocellular carcinoma via increasing triglyceride production.

The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss-of-function and gain-of-function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production.

The protective role of the miR-25-mediated notch signaling pathway in the memory capacity and brain tissue of mice with central nervous system infections.

OBJECTIVE: The study aimed to explore the role of miR-25 and the notch signaling pathway in the memory capacity and brain tissue of mice with central nervous system (CNS) infections. METHODS: A bioinformatics website and the dual-luciferase reporter assay were used to analyze the targeting relationship between miR-25 and Notch1. The mice were randomized into 7 groups (n=10 per group), including the normal group, the model group (lipopolysaccharide at a dose of 500 µg/kg for the model establishment), the NC group, the miR-25 mimic group, the miR-25 inhibitor group, the DAPT group, and the miR-25 inhibitor + DAPT group. qRT-PCR and western blot were used to measure the miR-25, Notch1, and Hes5 expression levels in the hippocampal CA1 region of the mice's brains, along with the cyclo-oxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) levels in the mice's hippocampi. RESULTS: Compared with the normal mice, the model mice had up-regulated miR-25, COX-2, and iNOS expressions and down-regulated Notch1 and Hes5 expressions, lower superoxide dismutase (SOD) levels in the hippocampi, and higher malondialdehyde (MDA) levels. Compared with the model group, the miR-25 mimic and DAPT groups had down-regulated Notch1 and Hes5 expressions, lower learning and memory capacities and SOD levels, higher MDA levels, and up-regulated COX-2 and iNOS expressions. CONCLUSION: Down-regulating miR-25 may improve the memory capacity in mice with CNS infections by activating the Notch signaling pathway.

MicroRNA-155 induces protection against cerebral ischemia/reperfusion injury through regulation of the Notch pathway in vivo.

microRNA (miR)-155 has been demonstrated to participate in the regulation of endothelium during cerebral ischemia. In the present study, it was aimed to investigate the molecular mechanism of miR-155 in the regulation of cerebral ischemia/reperfusion (I/R) injury with middle cerebral artery occlusion (MCAO) in mice. The MCAO model was established in C57BL/6 mice. Transfection of miR-155 mimics and miR-155 inhibitors was performed to alter the expression of miR-155. The level of miR-155 was measured by RT-qPCR analysis. The western blotting results demonstrated that deletion of miR-155 increased the expression of Notch1, intracellular Notch receptor domain (NICD) and hairy and enhancer of split-1 (Hes1) levels. In addition, the percentage of terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling-positive cells and caspase-3 levels were decreased following treatment with a miR-155 inhibitor compared with the Pre-IR group. Notably, disrupting miR-155 also increased nitric oxide (NO) production and the expression of endothelial NO synthase (eNOS), leading to downregulation of brain water content and Evans blue levels. However, overexpression of miR-155 restored all these changes to similar levels observed in the cerebral I/R injury group. The expressions of Notch1, NICD and Hes1 were also decreased to the cerebral I/R injury condition. In conclusion, a novel mechanism was identified for abrogating normal NO production and eNOS expression via the aberrant expression of the Notch signaling pathway, a mechanism that may be modulated by miR-155. Together, these results reveal important functions of miR-155 in regulating the Notch signaling pathway of the nervous system, and a potential role for miR-155 as a crucial therapy target for cerebral stroke.

Overexpression of PIK3R1 promotes hepatocellular carcinoma progression.

BACKGROUND: Phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) could regulate cancer cell proliferation important for cancer cell proliferation; however, its role in Hepatocellular carcinoma (HCC) remains largely unknown. Here, we investigated the role of PIK3R1 in HCC and examined the underlying molecular mechanisms. METHODS: The expression of PIK3R1 was evaluated by immunohistochemistry and qRT-PCR in a series of HCC tissues. The mRNA and protein expression of PIK3R1 was used by qRT-PCR and western blot assays in a series of human HCC cell lines, and then we choose MHCC97H and HCCLM3 cells as a model to investigate the effect of PIK3R1 on HCC progression. The effects of PIK3R1 knowdown on cell proliferation, migration, apoptosis of HCC were assessed by the MTT assay, clonogenic assays, wound healing assay and flow cytometry in vitro. Western blot assay was performed to assess the expression changes of PI3K/AKT/mTOR signaling pathway. RESULTS: Our results found that PIK3R1 was highly expressed in HCC tissues compared with adjacent normal tissues. Knockdown of PIK3R1 inhibited the proliferation, migration and promoted apoptosis of HCC cell lines. In addition, we proved that knockdown of PIK3R1 downregulated p-PI3K, p-AKT, and p-mTOR expressions in MHCC97H and HCCLM3 cells. CONCLUSIONS: In conclusion, PIK3R1 providing potential novel targets for the treatment of HCC.

miR-29b affects neurocyte apoptosis by targeting MCL-1 during cerebral ischemia/reperfusion injury.

The present study aimed to determine whether an miRNA (miR)-29b inhibitor protected against cerebral ischemia/reperfusion (I/R) injury in vitro and to investigate the underlying mechanisms. As a model for induced cerebral IR injury, N2a cells were exposed to an oxygen-glucose deprivation/reoxygenation (OGD/R) environment. Using this model, it was demonstrated that miR-29b was significantly upregulated compared with cells in a normal environment. The interactions between miR-29b and myeloid cell leukemia sequence (MCL)-1 were then investigated using dual-luciferase assays, revealing a strong regulation of MCL-1 through the 3'untranslated region. Using the OGD/R model, the present study additionally examined the effects of miR-29b and miR-29b inhibitor on cell viability and apoptosis using Cell Counting kit 8 and flow cytometry assays, respectively. miR-29b transfection led to increased N2a cell apoptosis and reduced cell viability under an OGD/R environment. However, this effect was reversed by the miR-29b inhibitor. Finally, the effects of miR-29b on the expression of several Wnt-associating proteins were examined. It was observed that B cell lymphoma-2 was inhibited by miR-29b, as was MCL-1, whereas caspase-3 expression was promoted. The miR-29b inhibitor demonstrated the opposite effect. Overall, miR-29b promoted neurocyte apoptosis by targeting MCL-1 during cerebral I/R injury. The results of the present study suggest a potential novel therapeutic target for the treatment of ischemic stroke.

miR­23b inhibits proliferation of SMMC­7721 cells by directly targeting IL­11.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer­associated mortality in the 21st century. microRNA (miR)­23b has been shown to be involved in the pathogenesis of many cancers, including breast and prostate cancer. However, the role of miR­23b in HCC remains unclear. The present study revealed a negative correlation between miR­23b expression in HCC tissues and progression of carcinomas. Compared to normal tissues, miR­23b expression was significantly downregulated in HCC tissues, whereas the expression of interleukin (IL)­11 and IL­11 receptor α (IL­11Rα) was significantly upregulated, indicating that miR­23b expression is negatively correlated with IL­11 and IL­11Rα expression. In addition, miR­23b inhibited proliferation and promoted apoptosis of SMMC­7721 cells. This effect was mediated by IL­11, which was found to be the direct target of miR­23b in this study. These results indicated that miR­23b regulates IL­11 and IL­11Rα expression, and might act as an anti­oncogenic agent in the progression of HCC by directly downregulating IL­11 expression.

MicroRNA-29b alleviates oxygen and glucose deprivation/reperfusion-induced injury via inhibition of the p53-dependent apoptosis pathway in N2a neuroblastoma cells.

Cerebral ischemic injury causes severe brain damage and remains one of the leading causes of morbidity and mortality worldwide. Members of the microRNA-29 (miR-29) family are involved in regulating the process of ischemia and may be developed as biomarkers to diagnose and treat cerebral ischemia. The role of miR-29b in cerebral ischemia injury remains poorly understood. The purpose of the present study was to investigate whether miR-29b overexpression suppressed cerebral ischemic injury and to explore its underlying mechanism of action. The results demonstrated that levels of miR-29b in N2a neuroblastoma cells decreased following oxygen and glucose deprivation/reperfusion (OGD/R) treatment. Transfection with miR-29b mimics significantly increased cell viability, decreased lactate dehydrogenase (LDH) leakage, inhibited apoptosis by decreasing morphological changes occurring in the nuclei and reduced caspase-3 activity in OGD/R-treated N2a cells. Conversely, miR-29b inhibitors enhanced OGD/R-induced cytotoxicity and apoptosis. In addition, the miR-29b mimics blocked the increase in Bax and p53 expression and decreased Bcl-2 expression in OGD/R-treated N2a cells, whereas miR-29b inhibitors exacerbated the changes in the expression of these apoptosis-associated proteins caused by OGD/R. p53 knockdown using p53 small interfering RNA decreased cell viability and increased LDH leakage, reversing the improvements that the miR-29b mimics induced in damaged cells. Taken together, the results of the present study demonstrated that miR-29b attenuates ischemic injury by negatively regulating the p53-dependent apoptosis pathway and may therefore be a novel potential therapeutic target for treating ischemic stroke.

Embolization of arterial gastrointestinal hemorrhage with Fuaile medical adhesive.

BACKGROUND: To investigate the safety and effectiveness of Fuaile medical adhesive (FAL) with superselective catheterization in endovascular embolotherapy for the treatment of gastrointestinal hemorrhage (GIH) that was unresponsive to internal medicine treatment and gastroscopy management. METHODS: A total of 25 patients with GIH, confirmed using angiography but with failed results after internal medicine treatment or gastroscopy were retrospectively analyzed. A mixture of lipiodol and FAL (1:1) was used to embolize the bleeding vessels. In the follow-up, the operation time, FAL amount, technical success rate, clinical success rate, postoperative complications, and survival conditions were compared and analyzed. RESULTS: Among the 25 patients with GIH, FAL was applied alone in 23 patients and microcoil combined with FAL was applied in two patients. Hemostasis was successfully achieved in all patients. Two patients treated with embolotherapy experienced relapse of bleeding within 30 days but achieved successful hemostasis with FAL. Four patients died during follow-up: three patients died of advanced cancer and one patient died of severe infection induced by necrotizing pancreatitis. Three patients developed postoperative intestinal ischemic symptoms, which resolved spontaneously in two patients. In one patient, abdominal pain progressively aggravated. This patient underwent surgical resection, which confirmed the presence of colonic neoplasms. The intraoperative view revealed obvious ischemia of the local normal bowel near the tumor; however, the patient finally recovered and was discharged after surgery. The remaining patients exhibited good survival during the postoperative follow-up. CONCLUSION: FAL embolotherapy has a high success rate for arterial GIH that was unresponsive to internal medicine treatment and gastroscopy management, with low postoperative rates of bleeding and complications; thus, this method has a high cost-efficacy.

Overexpression of PIK3R1 promotes hepatocellular carcinoma progression

BACKGROUND: Phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) could regulate cancer cell proliferation important for cancer cell proliferation; however, its role in Hepatocellular carcinoma (HCC) remains largely unknown. Here, we investigated the role of PIK3R1 in HCC and examined the underlying molecular mechanisms. METHODS: The expression of PIK3R1 was evaluated by immunohistochemistry and qRT-PCR in a series of HCC tissues. The mRNA and protein expression of PIK3R1 was used by qRT-PCR and western blot assays in a series of human HCC cell lines, and then we choose MHCC97H and HCCLM3 cells as a model to investigate the effect of PIK3R1 on HCC progression. The effects of PIK3R1 knowdown on cell proliferation, migration, apoptosis of HCC were assessed by the MTT assay, clonogenic assays, wound healing assay and flow cytometry in vitro. Western blot assay was performed to assess the expression changes of PI3K/AKT/mTOR signaling pathway. RESULTS: Our results found that PIK3R1 was highly expressed in HCC tissues compared with adjacent normal tissues. Knockdown of PIK3R1 inhibited the proliferation, migration and promoted apoptosis of HCC cell lines. In addition, we proved that knockdown of PIK3R1 downregulated p-PI3K, p-AKT, and p-mTOR expressions in MHCC97H and HCCLM3 cells. CONCLUSIONS: In conclusion, PIK3R1 providing potential novel targets for the treatment of HCC.

Pirfenidone Inhibits Proliferation and Promotes Apoptosis of Hepatocellular Carcinoma Cells by Inhibiting the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND Hepatocellular carcinoma (HCC) is the most important cause of cancer-related deaths worldwide. Pirfenidone is an orally available small molecule with therapeutic potential for fibrotic diseases. MATERIAL AND METHODS In this study, we analyzed the effects of different pirfenidone concentrations on the proliferation of HepG2 HCC cells using Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was performed to measure the apoptotic effects of pirfenidone on HepG2 cells. Western blot analysis was performed to detect the expression of ß-catenin and p-ß-catenin. RESULTS Pirfenidone inhibited proliferation and promoted HepG2 cell apoptosis. In addition, Western blot results indicated that pirfenidone suppressed b-catenin expression in HepG2 cells. To assess the mechanism, we treated HepG2 cells with pirfenidone, and pirfenidone plus the ß-catenin activator, SB-216763. The results revealed that SB-216763 accelerated proliferation and inhibited apoptosis in HepG2 cells treated with pirfenidone. Western blot results showed that SB-216763 upregulated ß-catenin expression in HepG2 cells treated with pirfenidone. CONCLUSIONS In conclusions, pirfenidone may be a potential drug for HCC treatment.

Experimental research of Fuaile medical adhesive for portal vein embolization in white rabbit models.

The aim of the present study was to investigate the feasibility and efficacy of Fuaile medical adhesive for portal vein embolization in the treatment of a rabbit model. This study used 26 white rabbits, 14 of which were selected and assigned into seven groups (n=2) for the preliminary experiment. Fuaile medical adhesive was mixed with lipiodol at different ratios of 1:0, 1:1, 1:2, 1:3, 1:4, 1:5 and 0:1, respectively, and administered via the portal trunk. The remaining 12 white rabbits were randomly divided into two groups (n=6). The evaluation of the results included the degree of adhesion to the vessels, the extent of embolization and the reaction of the rabbit. Hepatic and renal functions were detected prior to and at 1, 7 and 14 days post-embolization, respectively. Angiography, CT scans and pathological examinations were conducted at post-embolization. Histological examinations revealed that the topical swollen lesions were darker. Light microscopy showed embolic agents in the portal venous blood vessels and the formation of a secondary thrombus. Hepatic necrosis appeared surrounding the embolization area. Inflammatory cell infiltration of different degrees occurred in the early stage and inflammatory fibroplasia occurred in the late stage. Alanine aminotransferase and aspartate aminotransferase levels increased at 1 day post-embolization, peaked at 7 days and was in the normal range at 14 days. The levels of blood urea nitrogen and ceruloplasmin were elevated at 1 day post-embolization and lowered to normal at 7 days. Fuaile medical adhesive is an effective, safe and inexpensive agent, used for effectively inducing embolization in the portal trunk, and the first and second branches of rabbit portal veins. The use of Fuaile therefore merits widespread application in clinical practice.

Interferon-γ +874A/T polymorphism and hepatocellular carcinoma risk: a meta-analysis.

BACKGROUND: Studies have evaluated the association between interferon-γ (IFN-γ) +874A/T polymorphism and hepatocellular carcinoma (HCC) risk, but the results are controversial. We performed this meta-analysis to further investigate this association. MATERIAL AND METHODS: Relevant studies were searched by using the PubMed, Web of Science, and Embase databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Subgroup analysis and sensitivity analysis were conducted. RESULTS: Seven case-control studies (859 HCC patients and 1482 healthy controls) were identified to assess the association between IFN-γ +874A/T polymorphism and risk of HCC. IFN-γ +874A/T polymorphism was significantly associated with an increased risk of HCC (OR=1.38; 95% CI 1.12-1.70; P=0.002). In the subgroup analysis by ethnicity, IFN-γ +874A/T polymorphism was significantly associated with HCC risk in Asians (OR=1.42; 95% CI 1.08-1.87; P=0.01), but no significant association was found in Caucasians (OR=1.21; 95% CI 0.86-1.70; P=0.28). IFN-γ +874A/T polymorphism also increased HBV-induced HCC risk (OR=1.42; 95% CI 1.08-1.87; P=0.01). In the subgroup analysis by control source, IFN-γ +874A/T polymorphism was associated with HCC risk in hospital-based studies (OR=1.45; 95% CI 1.09-1.53; P=0.01). A marginal association was found in population-based studies (OR=1.33; 95% CI 0.97-1.83; P=0.08). CONCLUSIONS: This meta-analysis indicates that the IFN-γ +874A/T polymorphism might contribute to HCC risk.

Pirfenidone inhibits proliferation, arrests the cell cycle, and downregulates heat shock protein-47 and collagen type I in rat hepatic stellate cells in vitro.

Pirfenidone (esbiret) is an established anti-fibrotic and anti-inflammatory drug used to treat idiopathic pulmonary fibrosis. In the present study, the dose-dependent effects of pirfenidone on the cell cycle, proliferation and expression of heat shock protein (HSP)-47 and collagen type I in a cultured rat hepatic stellate cell line (HSC-T6) were investigated. Following pirfenidone treatment, cell proliferation was determined using the cell counting kit-8 assay and the cell cycle was measured using flow cytometry. HSP-47 expression was estimated using western blot analysis and collagen type I mRNA was assessed using reverse transcription quantitative polymerase chain reaction. Pirfenidone induced significant dose-dependent inhibition of proliferation in HSC-T6 cells. Cell viability was unaffected by treatment with pirfenidone (0, 10 or 100 µM) for 24 and 72 h. However, after 24 h, HSC-T6 cells exhibited dose-dependent decreases in HSP-47 protein and collagen I mRNA levels. In conclusion, pirfenidone inhibited HSC-T6 cell proliferation, arrested the cell cycle and reduced the expression of HSP-47 and collagen type I, indicating that pirfenidone may be a promising drug in the treatment of liver fibrosis.

Inositol-requiring enzyme 1-mediated endoplasmic reticulum stress triggers apoptosis and fibrosis formation in liver cirrhosis rat models.

Long­term and advanced cirrhosis is usually irreversible and often coincides with variceal hemorrhage or development of hepatocellular carcinoma; therefore, liver cirrhosis is a major cause of morbidity and mortality globally. The aim of the present study was to investigate the specific mechanism behind the formation of fibrosis or cirrhosis using rat models of hepatic fibrosis. The cirrhosis model was established by intraperitoneally administering dimethylnitrosamine to the rats. Hematoxylin and eosin staining was performed on the hepatic tissues of the rats to observe the fibrosis or cirrhosis, and western blot analysis was employed to detect α­smooth muscle actin and desmin protein expression. Flow cytometric analysis was used to examine early and late apoptosis, and the protein and mRNA expression of endoplasmic reticulum (ER) stress-associated unfolded protein response (UPR) pathway proteins and apoptotic proteins [C/EBP homologous protein (CHOP) and caspase­12] was detected by western blotting and the reverse-transcription polymerase chain reaction, respectively. The results indicated that the cirrhosis model was established successfully and that fibrosis was significantly increased in the cirrhosis model group compared with that in the normal control group. Flow cytometric analysis showed that early and late apoptosis in the cirrhosis model was significantly higher compared with that in the control group. The expression of the UPR pathway protein inositol-requiring enzyme (IRE) 1, as well as the expression of CHOP, was increased significantly in the cirrhotic rat tissues compared with that in the control group tissues (P<0.05). In conclusion, apoptosis was clearly observed in the hepatic tissue of cirrhotic rats, and the apoptosis was caused by activation of the ER stress-mediated IRE1 and CHOP.

Comparisons of cognitive function and serum S-100B level between diabetic and non-diabetic patients after the implantation of carotid artery stent (CAS).

To investigate cognitive function improvement in diabetic and non-diabetic patients after the implantation of Carotid Artery Stent (CAS), 128 patients suffering severe carotid stenosis were successfully enrolled in this study. Tests including, the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Clock Drawing Test (CDT), Hasegawa's Dementia Scale-Revised (HDS-R) and the serum levels of S-100B, were all measured at baseline for 3 months after the implantation of CAS. The baseline characteristics were similar between the patients with and without diabetes. 3 months after the implantation, significant improvements in MMSE (24.8 ± 2.2 vs. 25.2 ± 2.1, p=0.003), MoCA (25.6 ± 2.0 vs. 26.1 ± 1.9, p=0.000), ADAS-Cog (6.5 ± 1.3 vs. 6.1 ± 1.3, p=0.000), and CDT (3.3 ± 0.7 vs. 3.5 ± 0.7, p=0.034) were observed in the non-diabetic group. In contrast, there was no significant improvement in any of the cognitive test for the diabetic group. Another interesting discovery was the CAS procedure significantly decreased the S-100B level in the non-diabetic group (0.11 ± 0.04 ng/mL vs. 0.10 ± 0.04 ng/mL, p=0.000), but similar phenomena were not discovered in the diabetic group. In this light, the change of the S-100B level was negatively correlated with the results in the MMSE (p<0.01) and the MoCA (p<0.01) tests, and positively correlated with the result in ADAS-Cog (p<0.05) test. Our findings suggest that the CAS-induced beneficial effects on cognitive function might have a correlation relationship with the serum level of S-100B.