Interleukin-7 as a potential therapeutic target for alleviating hepatic fibrosis in a mice model induced by carbon tetrachloride: implications for fitness and exercise

The effects of interleukin-7 (IL-7) on the carbon tetrachloride (CCL4) induced hepatic fibrosis were investigated in this study. Thirty-six female BALB/C mice were randomized into group A (control group) injected with saline, group B (fibrotic model group) and group C (IL-7 intervention group). Histopathological changes were observed by HE, Masson as well as reticular fiber staining. The apoptosis cells and hepatic stellate cell (HSC) were detected from the tissues, and the expressions of Bax and Bcl-2 gene were also detected. The results of histological HE, Masson and reticular fiber staining showed that compared with group B, the degree of inflammation and fibrosis of the tissue were statistically reduced in group C. Compared with sub-group B and C, the degree of reduce inflammation of the liver and inhibit hepatic fibrosis were more obviously with the extension of treatment time. The inflammatory activity and liver fibrosis score were statistical significant between groups (P<0.05), the highest score was group B, followed by group C. The apoptosis cells were similar between fibrotic model group and IL-7 intervention group, while the HSC count was obviously higher in group B compared to the other two groups. The Bax gene was up-regulated when intervened with IL-7 for hepatic fibrosis and Bcl-2 showed to the contrary. IL-7 could inhibit hepatic fibrosis in mice induced by CCL4 and reduce liver inflammation process. The anti-fibrosis mechanism might be involved in inducing apoptosis through P53 pathway regulated Bcl-2 and Bax genes. (AU)

Human brucellosis and fever of unknown origin.

BACKGROUND: Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted. METHODS: We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records. RESULTS: The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05). CONCLUSION: Brucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis.

Rapid diagnosis of seven high-risk human papillomavirus subtypes by a novel loop-mediated isothermal amplification method.

Current human papillomavirus (HPV) detection methods require complex instruments, skilled staff and have a high cost. Therefore, novel testing approaches are needed which are easy to implement, highly sensitive, and low cost. Loop-mediated isothermal amplification (LAMP) is an isothermal amplification technique. In this study, according to the conditions in China, a novel LAMP method for detecting seven high-risk HPV subtypes (16, 18, 33, 39, 45, 52, and 58) was designed and evaluated. The DNA from plasmid and cervical specimens was extracted using Chelex 100 and measured by qPCR and LAMP assay. LAMP products were observed under ultraviolet light. HPV sequences were successfully amplified and a plateau time of 19-75 min was maintained. The concentration of positive reactions ranged between 20 copies/µL and 200000 copies/µL. Additionally, there was no cross-reactivity between HPV16, 18, 33, 39, 45, 52, 58, 31, 35, 45, 51, 56, 59, 66, or 68. For clinical samples, the LAMP assay had high sensitivity and specificity for HPV16, 18, 33, 39, 45, 52, and 58. However, 5% (72/1447) of the samples tested yielded false-positive results. In conclusion, the novel LAMP assay for HPV16, 18, 33, 39, 45, 52, and 58 has high sensitivity and specificity, a low cost, and is simple and rapid to perform. The LAMP assay can improve HPV detection in resource-limited settings, especially in primary care hospitals and rural areas.

Impact of the Gut Microbiome on the Progression of Hepatitis B Virus Related Acute-on-Chronic Liver Failure.

The relationship between the progression of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and the gut microbiota is poorly understood, and an HBV-ACLF-related microbiome has yet to be identified. In this study alterations in the fecal microbiome of 91 patients with HBV-ACLF (109 stool samples), including a cohort of nine patients at different stages of HBV-ACLF, were determined by high-throughput 16S rDNA sequencing. The operational taxonomic units and Shannon indexes indicated that the diversity and abundance of the gut microbiome significantly decreased with the progression of HBV-ACLF (p <0.05). The relative abundance of the Bacteroidetes phylum in the microbiome was significantly reduced, whereas the abundance of potentially pathogenic bacteria, such as Veilonella, Streptococcus, Enterococcus, and Klebsiella, was highly enriched in the HBV-ACLF group compared with the healthy control group. The abundance of Bacteroidetes was negatively correlated with the level of serum alpha fetoprotein, and the abundance of Veilonella was positively correlated with serum total bilirubin (TBIL). Furthermore, the abundance of Coprococcus was significantly negatively correlated with the level of serum TBIL and the international normalized ratio and positively correlated with prothrombin time activity. Our findings suggest that the gut microbiota plays an important role in the development of HBV-ACLF.

lncRNA SNHG7 sponges miR-425 to promote proliferation, migration, and invasion of hepatic carcinoma cells via Wnt/ß-catenin/EMT signalling pathway.

Increasing evidence has indicated the important roles of long noncoding RNA small nucleolar RNA host gene 7 (SNHG7) in tumourigenesis as a potential oncogene. However, the function of SNHG7 in hepatic carcinoma remains unclear. In the present study, we found that SNHG7 expression was significantly upregulated in hepatic carcinoma tissues, especially in aggressive cases, and it was closely correlated with the poor prognosis. Furthermore, knockdown of SNHG7 inhibited the proliferation, migration, and invasion of hepatic carcinoma cell lines in vitro. Mechanistically, SNHG7 directly interacted with miR-425 as a ceRNA. Moreover, knockdown of SNHG7 significantly inhibited the tumorigenic Wnt/ß-catenin/EMT pathway. SNHG7 regulated Wnt/ß-catenin/EMT pathway through sponging miR-425 and played an oncogenic role in hepatic carcinoma progression. Together, our study elucidated the role of SNHG7 as a ceRNA in hepatic carcinoma, provided new potential diagnosis and therapeutic application in hepatic carcinoma progression. SIGNIFICANCE OF THE STUDY: SNHG7 could promote proliferation and metastasis of hepatic carcinoma cell in vitro and in vivo, suggesting that SNHG7 exerts tumorigenic role in hepatic carcinoma progression. Further mechanism research revealed that SNHG7 exhibited the tumorigenic role through Wnt/ß-catenin/EMT pathway as a miR-425 sponge. These findings provided new cues to understand the molecular signalling network in carcinogenesis of hepatic carcinoma, and it may provide new evidence for therapeutic application in hepatic carcinoma.

Improved drug targeting to liver tumor by sorafenib-loaded folate-decorated bovine serum albumin nanoparticles.

BACKGROUND: To prepare sorafenib-loaded folate-decorated bovine serum nanoparticles (FA-SRF-BSANPs) and investigate their effect on the tumor targeting. METHODS: The nanoparticles were characterized and evaluated by in vivo and in vitro experiments. RESULTS: SRF-loaded BSA nanoparticles (SRF-BSANPs) was first prepared and modified with folic acid by chemical coupling to obtain FA-SRF-BSANPs. The average particle size, zeta potential, entrapment efficiency, and drug loading of the optimized FA-SRF-BSANPs were 158.00 nm, -16.27 mV, 77.25%, and 7.73%, respectively. The stability test showed that FA-SRF-BSANPs remained stable for more than 1 month at room temperature. The TEM analysis showed that the surface of FA-SRF-BSANPs was nearly spherical. XRD analysis showed that the drug existed in. the nanoparticles in an amorphous state. FA-SRF-BSANPs can promote the intracellular uptake of hepatoma cells (SMMC-7721) with the strongest inhibitory effect compared with SRF-BSANPs and sorafenib solution. Furthermore, the tumor targeting of FA-SRF-BSANPs (Ctumor/Cblood, 0.666 ± 0.053) was significantly higher than those of SRF-BSANPs (Ctumor/Cblood, 0.560 ± 0.083) and sorafenib-solution (Ctumor/Cblood, 0.410 ± 0.038) in nude mice with liver cancer. CONCLUSION: FA-modified albumin nanoparticles are good carriers for delivering SRF to the tumor tissue, which can improve the therapeutic effect and reduce the side effects of the drug.