Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by dysregulation of lipid metabolism, insulin resistance, and gut microbiota disorder. Compared to drug interventions, probiotic interventions may have a more enduring effect without producing any side effects. Thus, the potential of probiotics as a therapeutic approach for diabetes and other metabolic disorders has gained increasing attention in recent years. In this study, we evaluated the therapeutic efficacy of Lactobacillus gasseri CKCC1913, a potential probiotic strain, in high-fat diet-induced insulin-resistant diabetes using the C57BL/6J mouse animal model. From the results, L. gasseri CKCC1913 has been shown to increase glucose tolerance, reduce fasting blood glucose levels in diabetic mice, and reduce the expression of pro-inflammatory cytokines, such as TNF-α and IL-6. Besides, L. gasseri CKCC1913 intervention effectively alleviated oxidative stress damage by increasing SOD activity, decreasing MDA levels, reducing insulin resistance, and improving dyslipidemia caused by diabetes. The potential mechanism of L. gasseri CKCC1913 in improving metabolic health and alleviating diabetes involves an increased abundance of beneficial bacteria, such as Parabacteroides merdae, which directly produce short-chain fatty acids that help regulate immune cells and reduce inflammation. SCFAs also enter the bloodstream and promote antioxidant enzyme activity in the liver, protecting against oxidative damage. Additionally, L. gasseri CKCC1913 influences local bacterial metabolism pathways, such as the superpathway of unsaturated fatty acid biosynthesis, leading to an increase in unsaturated fatty acids, increasing high-density lipoprotein cholesterol (HDL-C) levels and improving lipid metabolism and glucose control in diabetic mice. In summary, in this study, L. gasseri CKCC1913 and its potential impact on metabolic health highlight the promising potential of probiotics as a therapeutic approach for diabetes. Future research should focus on identifying the optimal dose and duration, investigating the long-term effects and mechanisms of action, and exploring the potential use of probiotics as an adjunct to other therapies or in preventing metabolic disorders.

Microvessel density (MVD) has been proposed as a direct quantification method of tumor neovascularization. However, the current literature regarding the role of MVD in differentiated thyroid carcinoma (DTC) remains inconclusive.

To appraise the effect of tumoral MVD on the survival of patients with DTC.

This meta-analysis was based on the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The electronic databases Medline, Web of Science, and Scopus were systematically screened. A fixed-effects or random-effects model was used, according to the Cochran Q test. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/).

A total of nine studies were included in the present study. Superiority of low MVD tumors in terms of 10-year disease free survival (OR: 0.21, 95%CI: 0.08-0.53) was recorded. Lowly vascularized thyroid cancers had a lower recurrence rate (OR: 13.66, 95%CI: 3.03-61.48). Moreover, relapsing tumors [weighed mean difference (WMD): 11.92, 95%CI: 6.32-17.52] or malignancies with regional lymph node involvement (WMD: 8.53, 95%CI: 0.04-17.02) presented with higher tumoral MVD values.

MVD significantly correlates with the survival outcomes of thyroid cancer patients. However, considering several study limitations, further prospective studies of higher methodological and quality level are required.

Liver cirrhosis (LC) is a heterogeneous liver disease, the last stage of liver fibrosis, and the major risk factor for hepatocellular carcinoma (HCC). Our study aimed to evaluate the expression of microRNAs and the endothelial vascular growth factor (VEGFA) gene in LC and HCC.

The sample group consisted of 46 tissue samples: 21 of LC, 15 of HCC, and 10 of non-tumoural and non-cirrhotic liver tissue (control group). MiRNAs were chosen based on a mirDIP prediction database as regulators of the VEGFA gene. Gene expression of VEGF and miRNAs was quantified by real-time quantitative polymerase chain reaction. VEGFA protein expression was evaluated by ELISA.

VEGFA gene expression was significantly overexpressed in LC compared to the control group (p < 0.0001). Hsa-miR-206 (p = 0.0313) and hsa-miR-637 (p = 0.0156) were down-expressed in LC. In HCC, hsa-miR-15b (p = 0.0010), hsa-miR-125b (p = 0.0010), hsa-miR-423-3p (p = 0.0010), hsa-miR-424 (p = 0.0313), hsa-miR-494 (p < 0.0001), hsa-miR-497 (p < 0.0001), hsa-miR-612 (p = 0.0078), hsa-miR-637 (p < 0.0001), and hsa-miR-1255b (p = 0.0156) presented down-expression.

Overexpression of VEGFA in LC suggests impairment of angiogenesis in this tissue. The differential expression of microRNAs in LC and HCC observed in our study can lead to the evaluation of possible biomarkers for these diseases.

The progression of fibrosis in chronic hepatitis C (CHC) is a multifactorial process. The high adverse effects and the cost of standard health care increase the demand to discover new predictors for the progression of fibrosis in CHC patients. Our study aims to establish the relation between the angiogenic marker [vascular endothelial growth factor (VEGF)] and activated hepatic stellate cells (HSCs) represented by the expression of α-smooth muscle actin (α-SMA) and whether these 2 markers can be used as predictors for the progression of fibrosis in patients with CHC.

Histopathologic and immunohistochemical analyses were used for examining the morphology and the expression of VEGF and α-SMA in 60 CHC biopsies procured from CHC patients. Multivariate analysis was used to correlate the protein expression with staging and grading of liver fibrosis. Cutoff values of α-SMA and VEGF were determined by the receiver operating characteristics curve.

There was a positive correlation between VEGF and HSCs expressing α-SMA (ρ=0.287, P=0.026) and both factors were correlated with the stage of fibrosis (P<0.001). Using the receiver operating characteristics curve, both VEGF (area under the curve=0.71, P<0.006) and α-SMA (area under the curve=0.82, P<0.001) were positive predictors for moderate and severe fibrosis.

This study demonstrates the relation between VEGF expression and the activated HSCs denoted by the expression of α-SMA in CHC biopsies and together can be used as a predictor for the progression of fibrosis.

Boswellic acid (BA)-containing extracts such as BSE have anti-inflammatory and immunomodulatory activity. In chronic schistosomiasis, the hepatic granuloma and fibrosis induced by egg deposition in the liver is the most serious pathological manifestations. However, little is known regarding the role of BAs in Schistosoma japonicum (S. japonicum) egg-induced liver granuloma and fibrosis. In order to investigate the effect of a water-soluble complex preparation of BSE, BSE-CD, on S. japonicum egg-induced liver pathology, liver granuloma and fibrosis were induced by infecting C57BL/6 mice with 18-22 cercariae of S. japonicum. S. japonicum cercariae infected mice were injected with BSE-CD at the onset of egg granuloma formation (early phase BSE-CD treatment after 4 weeks infection) or after the formation of liver fibrosis (late phase BSE-CD treatment after 7 weeks infection). Our data show that treatment of infected mice with BSE-CD significantly reduced both the extent of hepatic granuloma and fibrosis. Consistent with an inhibition of NF-κB signaling as evidenced by reduced IκB kinase (IKK) activation, the mRNA expression of VEGF (vascular endothelial growth factor, VEGF), TNF-α (tumor necrosis factor-alpha TNF-α) and MCP-1 (monocyte chemotactic protein 1, MCP-1) was decreased. Moreover, immunohistochemical analysis (IHC) revealed that the content of α-SMA in liver tissue of BSE-CD treated mice was dramatically decreased. Our findings suggest that BSE-CD treatment attenuates S. japonicum egg-induced hepatic granulomas and fibrosis, at least partly due to reduced NF-κB signaling and the subsequently decreased expression of VEGF, TNF-α, and MCP-1. Suppression of the activation of hepatic stellate cells (HSC) may also be involved in the therapeutic efficacy of BSE-CD.

Hepatitis C imposes a significant burden on global healthcare. Chronic infection is associated with progressive inflammation of the liver which typically manifests in cirrhosis, organ failure and cancer. By virtue of elaborate evasion strategies, hepatitis C virus (HCV) succeeds as a persistent human virus. It has an extraordinary capacity to subvert the immune response enabling it to establish chronic infections and associated liver disease. Chemokines are low molecular weight chemotactic peptides that mediate the recruitment of inflammatory cells into tissues and back into the lymphatics and peripheral blood. Thus, they are central to the temporal and spatial distribution of effector and regulatory immune cells. The interactions between chemokines and their cognate receptors help shape the immune response and therefore, have a major influence on the outcome of infection. However, chemokines represent a target for modulation by viruses including the HCV. HCV is known to modulate chemokine expression in vitro and may therefore enable its survival by subverting the immune response in vivo through altered leukocyte chemotaxis resulting in impaired viral clearance and the establishment of chronic low-grade inflammation. In this review, the roles of chemokines in acute and chronic HCV infection are described with a particular emphasis placed on chemokine modulation as a means of immune subversion. We provide an in depth discussion of the part played by chemokines in mediating hepatic fibrosis while addressing the potential applications for these chemoattractants in prognostic medicine.

Increasing evidence supports the hypothesis that chronic and persistent inflammation contributes to cancer development. However, the molecular mechanisms that lead to cancer in chronic inflammation and the role of angiogenesis in inflammation-associated cancer remain poorly understood.

NINETY PATIENTS WERE ENROLLED: 30 cases of CHC without cirrhosis, 28 cases of CHC with liver cirrhosis, and 32 cases of HCC and hepatitis C virus infection. Ten wedge liver biopsies, taken during laparoscopic cholecystectomy, served as normal controls. Serum TNF-α levels were measured using the ELISA technique; in situ hybridization and immunohistochemical studies were used to detect hepatic levels of messenger RNA (mRNA) transcripts and mature protein, respectively, for both TNF-α and VEGF.

The highest hepatic expression of TNF-α was noticed in liver cirrhosis specimens compared to noncirrhotic CHC and HCC. Hepatic expression of VEGF and serum level of TNF-α revealed significant increases in the progression of the disease. Moreover, cases with higher grades of inflammation or stages of fibrosis showed significant increases in serum TNF-α and expression of TNF-α and VEGF. Expression of mRNA of both TNF-α and VEGF shows increasing expression with positive correlation to progression of viral hepatitis to cirrhosis with more positivity in cases developed HCC.

VEGF signaling could be one of the molecular signaling pathways involved in TNF-α induced angiogenesis which might pose an important link between inflammation and fibrosis in CHC and HCC development and progression. Moreover, serum inflammatory biomarkers can be used to monitor the disease progression.

During peritoneal dialysis (PD), exposure of the peritoneal membrane to nonphysiologic solutions causes inflammation, ultimately leading to altered structure and function. Myofibroblasts, one of the cell types that contribute to dysfunction of the peritoneal membrane, can originate from mesothelial cells (MCs) by epithelial-to-mesenchymal transition (EMT), a process that has been associated with an increased rate of peritoneal transport. Because cyclooxygenase-2 (COX-2) is induced by inflammation, we studied the role of COX-2 in the deterioration of the peritoneal membrane. We observed that nonepithelioid MCs found in peritoneal effluent expressed higher levels of COX-2 than epithelioid MCs. The mass transfer coefficient for creatinine correlated with MC phenotype and with COX-2 levels. Although COX-2 was upregulated during EMT of MCs in vitro, COX-2 inhibition did not prevent EMT. In a mouse model of PD, however, COX-2 inhibition with Celecoxib resulted in reduced fibrosis and in partial recovery of ultrafiltration, outcomes that were associated with a reduction of inflammatory cells. Furthermore, PD fluid with a low content of glucose degradation products did not induce EMT or COX-2; the peritoneal membranes of mice treated with this fluid showed less worsening than mice exposed to standard fluid. In conclusion, upregulation of COX-2 during EMT may mediate peritoneal inflammation, suggesting COX-2 inhibition as a potential strategy to ameliorate peritoneal deterioration in PD patients.

To investigate the effect of vascular endothelial growth factor (VEGF) transfection on hepatic sinusoidal capillarization.

Enhanced green fluorescent protein (EGFP)/VEGF transfection was confirmed by immunofluorescence microscopy and immunohistochemistry both in primary hepatocytes and in normal liver. Cirrhotic rats were generated by thioacetamide (TAA) administration and then divided into a treatment group, which received injections of 400 microg of plasmid DNA encoding an EGFP-VEGF fusion protein, and a blank group, which received an equal amount of normal saline through the portal vein. The portal vein pressure was measured in the normal and cirrhotic state, in treated and blank groups. The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy (TEM), while the relative abundance of VEGF transcripts was examined by Gene array.

Green fluorescent protein was observed in the cytoplasms of liver cells under immunofluorescence microscopy 24 h after transfection with EGFP/VEGF plasmid in vitro. Staining with polyclonal antibodies against VEGF illustrated that hepatocytes expressed immunodetectable VEGF both in vitro and in vitro. There were significant differences in the number of fenestrae and portal vein pressures between normal and cirrhotic rats (7.40 +/- 1.71 vs 2.30 +/- 1.16 and 9.32 +/- 0.85 cmH2O vs 17.92 +/- 0.90 cmH2O, P < 0.01), between cirrhotic and treated rats (2.30 +/- 1.16 cmH2O vs 4.60 +/- 1.65 and 17.92 +/- 0.90 cmH2O vs 15.52 +/- 0.93 cmH2O, P < 0.05) and between the treatment group and the blank group (4.60 +/- 1.65 cmH2O vs 2.10 +/- 1.10 cmH2O and 15.52 +/- 0.93 cmH2O vs 17.26 +/- 1.80 cmH2O, P < 0.05). Gene-array analysis revealed that the relative abundance of transcripts of VEGF family members decreased in the cirrhotic state and increased after transfection.

Injection of a plasmid encoding VEGF through the portal vein is an effective method to induce the formation of fenestrae and decrease portal vein pressure in cirrhotic rats. Therefore, it may be a good choice for treating hepatic cirrhosis and portal hypertension.