This study is performed to analyze the anti-liver fibrosis effect of the fusion protein of human serum albumin and extracellular domain of transforming growth factor beta type II receptor(eTGFBR2)in vivo to looking for the more stable anti-liver fibrosis drug. The mice model of liver fibrosis was constructed by CCl4 induction and the following groups are included in the study: the control group, CCl4 model group, the positive control group, eTGFBR2 treatment group, HSA-eTGFBR2 treatment group, and HSA group. Hematoxylin eosin staining, serum liver function index detection, and western blot are used to identify the anti-liver fibrosis activities. The results showed that: (1)CCl4 caused liver structure disorder, hepatocellular necrosis, collagen fibers proliferation, and induced liver fibrosis at last; (2)HSA-eTGFBR2 and its monomer drug improved the symptoms of liver fibrosis significantly, as well as reduced the damage of liver cells and collagen deposition, and recovered the liver basic structure to normal. Both of HSA-eTGFBR2 and its monomer drug improved liver function and reduced the expression level of liver fibrosis marker α-SMA and COL I. Moreover, the anti-liver fibrosis effect of the fusion protein is comparable to the monomer drug. In contrast, the albumin had no effect on therapeutic effect; (3)Reducing the injection frequency of HSA-eTGFBR2 achieved the comparable effects to the monomer drug with the normal injection frequency. In summary, the fusion protein HSA-eTGFBR2 has good anti-liver fibrosis effect. In addition, reducing the injection frequency of the fusion protein could also achieve the comparable treatment with the monomer drug, indicating that the fusion protein is stable and has longer half-lives and then a relatively positive application prospect in future.

Liver fibrosis is a common chronic liver disease, which is a stress response process of liver cells affected by one or more pathogenies for long term or repeatedly. During the fibrosis process, massive accumulated extracellular matrix can form scar tissue, which results in liver dysfunction or failure and seriously endangers the health of people. According to many independent reports, stem cell therapy can facilitate the alleviation of liver fibrosis. During the stem cell therapy, stem cells migrate to the injury site of liver and alleviate the liver fibrosis by improving the microenvironment of the scar area via paracrine way. This article reviews the formation, treatment, and stem cell therapy of liver fibrosis.

This study was focus on investigating the anti-liver fibrosis effects of insulin-like growth factor-1 (IGF-1) in vitro.The effects of IGF-1 on human liver L-02 cell viability and cell cycle were observed.CC14-induced L-02 cell injury was set up to detect the anti-apoptotic activity of insulin-like growth factor-1 (IGF-1).Transforming growth factor β1 (TGF-β1) induced hepatic stellate cell line (HSC-T6) were used as a liver fibrosis model in vitro to analyze the effects of IGF-1 on the expression of liver fibrosis proteins and intracellular TGF-β1/Smad signaling pathway in HSC-T6 cells.The results showed that IGF-1 could relieve the growth inhibition effects of TGF-β1 on L-02 cells,increase the viability of L-02 cells injured by CCl4,decrease the expression of liver fibrosis proteins,and inhibit the TGF-β1/Smad signaling pathway by inhibiting the phosphorylation of Smad3.Our study suggested that IGF-1 exerted anti-liver fibrosis effects by stimulating L-02 cells proliferation,reducing cell damage and inhibiting ECM accumulation via interfering TGF-β1/Smad signaling pathway.

Introduction: This multiple-subject fMRI study continue to further investigate brain activation within and effective connectivity between the significantly (p<0.001) activated primary motor area (M1), supplementary motor area (SMA) with the inclusion of BA44 during unimanual (UNIright and UNIleft) and bimanual (BIM) self-paced tapping of hand fingers. Methods: The activation extent (spatial and height) and effective connectivity were analysed using statistical parametric mapping (SPM), dynamic causal modeling (DCM) and the novel method of Bayesian model selection (BMS) for group studies. Results: Group results for UNIright and UNIleft showed contra-lateral and ipsi-lateral involvement of M1 and SMA. The results for BIM showed bilateral activation in M1, SMA and BA44. A larger activation area but with lower percentage of signal change (PSC) are observed in the left M1 due to the control on UNIright as compared to the right M1 due to the control on UNIleft. This is discussed as due to the influence of the tapping rate effects that is greater than what would be produced by the average effects of the dominant and sub-dominant hand. However, the higher PSC observed in the right M1 is due to a higher control demand used by the brain in coordinating the tapping of the sub-dominant hand fingers. Connectivity analysis indicated M1 as the intrinsic input for UNIright and UNIleft while for BIM, the inputs were both M1s. During unilateral finger tapping, the contra-lateral M1 acts as the input center which in turn triggers the propagation of signal unidirectionally to other regions of interest. The results obtained for BIM (BIMleft and BIMright) however yield a model with less number of significant connection. M1-M1 connection is unidirectional for UNIleft and UNIright originating from contra-lateral M1, and is inhibited during BIM. Conclusion: By taking into consideration the presence of outliers that could have arisen in any subject under study, BMS for group study has successfully chosen a model that has the best balance between accuracy (fit) and complexity.

Objective: This study investigates functional specialisation in, and effective connectivity between the precentral gyrus (PCG) and supplementary motor area (SMA) in seven right handed female subjects. Methods: Unimanual (UNIright and UNIleft) and bimanual (BIM) self-paced tapping of hand fingers were performed by the subjects to activate PCG and SMA. Brain activations and effective connectivity were analysed using statistical parametric mapping (SPM), dynamic causal modeling (DCM) and Bayesian model selection (BMS) and were reported based on group fixed (FFX) and random (RFX) effects analyses. Results: Group results showed that the observed brain activation for UNIright and UNIleft fulfill contralateral behavior of motor coordination with a larger activation area for UNIright. The activation for BIM occurs in both hemispheres with BIMright showing higher extent of activation as compared to BIMleft. Region of interest (ROI) analyses reveal that the number of activated voxel (NOV) and percentage of signal change (PSC) on average is higher in PCG than SMA for all tapping conditions. However, comparing between hemispheres for both UNI and BIM, higher PSC is observed in the right PCG and the left SMA. DCM and BMS results indicate that most subjects prefer PCG as the intrinsic input for UNIright and UNIleft. The input was later found to be bi-directionally connected to SMA for UNIright.The bi-directional model was then used for BIM in the left and right hemispheres. The model was in favour of six out of seven subjects. DCM results for BIM indicate the existance of interhemispheric connectivity between the right and left hemisphere PCG. Conclusion: The findings strongly support the existence of functional specialisation and integration i.e. effective connectivity in human brain during finger tapping and can be used as baselines in determining the probable motor coordination pathways and their connection strength in a population of subjects

Ginger extract has been reported previously by our group to exhibit anticancer and antioxidant effects by reducing tumour burden and lipid peroxidation respectively in he-patocarcinogenesis induced rats. The current study examined the expression of pro-apoptotic protein caspase-8 and anti-apoptotic protein Bcl-2 in hepatocarcinogenesis treated rats. Thirty normal male Wistar rats were divided into 5 groups based on the diet given: i) control (normal rat chow), ii) olive oil, iii) ginger extract (100mg/kg body weight), iv) choline deficient diet + ethionine, CDE (to induce liver cancer) and v) CDE+ginger extract. Rats were killed at week 8, and liver tissues were excised for immuno-histochemical study to identify pro-apoptotic and anti-apoptotic proteins, caspase-8 and Bcl-2. The observation on H&E staining confirmed the CDE diet induced liver can-cer as indicated by the presence of numerous oval cells. Identification of Bcl-2 expres-sion showed that 91.6% (11/12) of the samples from the CDE group revealed positive staining while treatment with ginger extract however inhibited the expression with only 8.4% (1/12) samples showing positive staining for Bcl-2. As for caspase-8 protein, 41.7% (5/12) of the samples from CDE group showed positive staining, which in-creased to 100% (12/12) with ginger extract treatment. Our findings suggest that gin-ger extract has an anticancer effect by inducing apoptosis in liver cancer cells via up-regulation of the expression of pro-apoptotic protein, caspase-8 and down-regulation of the expression of anti-apoptotic protein Bcl-2.

Chlorella vulgaris (CV) has been reported to have antioxidant and anticancer properties. We evaluated the effect of CV on apoptotic regulator protein expression in liver cancer-induced rats. Male Wistar rats (200~250 g) were divided into eight groups: control group (normal diet), CDE group (choline deficient diet supplemented with ethionine in drinking water to induce hepatocarcinogenesis), CV groups with three different doses of CV (50, 150, and 300 mg/kg body weight), and CDE groups treated with different doses of CV (50, 150, and 300 mg/kg body weight). Rats were sacrificed at various weeks and liver tissues were embedded in paraffin blocks for immunohistochemistry studies. CV, at increasing doses, decreased the expression of anti-apoptotic protein, Bcl-2, but increased the expression of pro-apoptotic protein, caspase 8, in CDE rats, which was correlated with decreased hepatocytes proliferation and increased apoptosis as determined by bromodeoxy-uridine (BrdU) labeling and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay, respectively. Our study shows that CV has definite chemopreventive effect by inducing apoptosis via decreasing the expression of Bcl-2 and increasing the expression of caspase 8 in hepatocarcinogenesis-induced rats.
Animals ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Cell Proliferation ; drug effects ; Chlorella vulgaris ; chemistry ; Dietary Supplements ; Liver Neoplasms ; diet therapy ; metabolism ; pathology ; Male ; Plant Extracts ; administration & dosage ; Rats ; Rats, Wistar ; Treatment Outcome

Introduction: Rapid detection of influenza viruses and respiratory syncytial virus (RSV) can be achieved by having rapid molecular point of care tests (POCTs). This expedites the diagnosis attributed by having similar clinical presentations leading to facilitation of precision medicine and reduction of antimicrobial resistance. The growing number of POCTs foster the need to ensure that these POCTs have satisfactory and reliable performance. With that the aim of this study is to evaluate the performance of rapid molecular POCT regarded as ‘X’ for the detection of Influenza viruses and RSV in comparison to multiplex PCR. Methods: A laboratory-based study was conducted from January to December 2020 which involved analysis of 116 nasopharyngeal swabs, tested using POCT X and multiplex PCR as a method of reference. The performance analysis incorporated the sensitivity, specificity, positive and negative predicted values determination. The cycle threshold values were reviewed for discordant results. Results: The POCT X demonstrated sensitivity of 88.57% with 100% specificity for Influenza A virus, and 85.71% of sensitivity with 100% specificity for influenza B virus detection. Meanwhile it revealed 100% sensitivity and specificity for RSV detection. There were ten specimens demonstrating discordant results whereby viruses were not detected by POCT X, however detected by multiplex PCR. The POCT X was not able to detect eight (12.9%) and two (16.7%) influenza A and B viruses respectively. Conclusion: The overall performance of POCT X was corresponded to multiplex PCR. This best served as a steadfast ancillary test for influenza and RSV infection.