Sesamol promotes browning of white adipocytes through liver-adipose crosstalk signal of hepatic fibroblast growth factor 21.

Sesamol (SEM), a lignan from sesame oil, exhibited potential benefits on obesity treatment by promoting browning of adipocytes, and the current study is aimed to explore the molecular mechanisms of SEM from the aspect of systemic liver-adipose crosstalk that mediated by hepatic fibroblast growth factor 21 (FGF21). Our in vivo data showed that SEM induced energy expenditure and white adipose tissue (WAT) browning by increasing the expression level of uncoupling protein-1 in high fat diet induced obese C57BL/6J mice. Elevated levels of circulating FGF21 associated with the increased expression of hepatic FGF21 were observed after SEM intervention. Simultaneously, the increased adipose fibroblast growth factor tyrosine kinase receptor 1/beta-klotho indicated that FGF21 sensitivity was enhanced by SEM in WAT. Furthermore, our in vitro results from HepG2 and 3T3-L1 cell lines confirmed the effects and revealed the mechanism of SEM on the white adipocytes browning. We found that with the specific inhibitors of PPARα, the SEM-mediated hepatic FGF21 expression was decreased, and with the specific inhibitors of PPARγ, the browning effect of adipocytes by SEM combining with FGF21 was significantly suppressed. Taken together, the mechanism of SEM for inducing the WAT browning might be the modulation of SEM on liver-adipose crosstalk mediated by FGF21, and the PPARs family might be the targets of SEM. The novel findings from the present study provided evidence that SEM could be a potent obesity-treating compound.

Application of Immune Checkpoint Inhibitors in the Treatment of Cholangiocarcinoma.

Cholangiocarcinoma is a general term for intrahepatic and extrahepatic malignant tumors deriving in the biliary system. According to the location, it is divided into intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and distal cholangiocarcinoma. Progressive cholangiocarcinoma yields poor outcomes with radiotherapy; therefore, there is an urgent need for new therapeutic breakthroughs. Immune checkpoint inhibitor (ICI) therapy brings the treatment for cancer into a new field, with the use of drugs targeting PD-1/PD-L1 and CTLA-4 considerably extending the survival of patients with melanoma, lung cancer, and other solid tumors. The FDA has approved the application of pembrolizumab for solid tumors with high microsatellite instability and defective mismatch repair, including cholangiocarcinoma. Moreover, the combination of ICIs with chemotherapy and radiation therapy showed good promise. The aim of the present study was to review the application of ICIs in the treatment of cholangiocarcinoma and to summarize the reported individualized immunotherapy-based protocols and ongoing clinical trials for clinical reference.

Whole-genome sequencing of leopard coral grouper ( Plectropomus leopardus) and exploration of regulation mechanism of skin color and adaptive evolution.

Leopard coral groupers belong to the Plectropomus genus of the Epinephelidae family and are important fish for coral reef ecosystems and the marine aquaculture industry. To promote future research of this species, a high-quality chromosome-level genome was assembled using PacBio sequencing and Hi-C technology. A 787.06 Mb genome was assembled, with 99.7% (784.57 Mb) of bases anchored to 24 chromosomes. The leopard coral grouper genome size was smaller than that of other groupers, which may be related to its ancient status among grouper species. A total of 22 317 protein-coding genes were predicted. This high-quality genome of the leopard coral grouper is the first genomic resource for Plectropomus and should provide a pivotal genetic foundation for further research. Phylogenetic analysis of the leopard coral grouper and 12 other fish species showed that this fish is closely related to the brown-marbled grouper. Expanded genes in the leopard coral grouper genome were mainly associated with immune response and movement ability, which may be related to the adaptive evolution of this species to its habitat. In addition, we also identified differentially expressed genes (DEGs) associated with carotenoid metabolism between red and brown-colored leopard coral groupers. These genes may play roles in skin color decision by regulating carotenoid content in these groupers.

The role of enterovirus 71 and coxsackievirus A strains in a large outbreak of hand, foot, and mouth disease in 2012 in Changsha, China.

BACKGROUND: During 2012, Changsha experienced a large outbreak of hand, foot, and mouth disease (HFMD), resulting in 25,438 cases, including 42 severe cases and eight deaths. METHODS: Seven hundred and forty-six clinical specimens were collected from hospital-based surveillance for HFMD in 2012. The detection and genotyping of enterovirus were performed by real-time RT-PCR and sequencing of the VP1 regions; phylogenetic analysis was performed based on the VP1 sequences. RESULTS: A total of 545 (73.1%) enterovirus-positive samples were identified, with the most frequently presenting serotype being enterovirus 71 (EV-71; n=364, 66.8%), followed by coxsackievirus A16 (CV-A16; n=84, 15.4%), CV-A6 (n=22, 4.0%), and CV-A10 (n=19, 3.5%). Most of the affected patients were children aged ≤5 years (n=524, 96.1%). EV-71 was the major pathogen in the severe and fatal cases (n=22, 78.6%). Phylogenetic analysis of VP1 gene sequences showed the EV-71 isolates to belong to subgenotype C4a, and the CV-A16 isolates to belong to subgenotype B1. The Changsha CV-A6 and CV-A10 circulating strains were homologous to strains circulating in other areas of mainland China. CONCLUSIONS: Our results demonstrate that EV-71 was the primary causative agent responsible for the HFMD outbreak in Changsha in 2012, and the co-circulation of other coxsackievirus A strains posed a potential risk to public health.

Surveillance of influenza virus during 2010-2012 in Changsha, China.

The objective of this study was to examine the circulating influenza viruses in Changsha, China, during 2010-2012. Nasopharyngeal specimens were collected from persons with influenza-like illness (ILI) who presented for care at two hospitals. Of 2,955 patients tested, 278/(9.4%) were positive for influenza virus: 116/(41.7%) were influenza type A(H3N2), 79/(28.4%) were type A(H1N1) pandemic 2009 (pdm09) and 83/(29.9%) were influenza type B. The rates of virus detection varied by age and sex. The highest rate was in the 5-14 year old age group and females were infected more than males. After the initial 2009 A(H1N1) pdm09 outbreak, the number of cases of this virus declined and the season become shorter. Influenza A(H3N2) and B viruses occurred mainly during the spring and summer, while influenza A(H1N1)pdm09 occurred mainly during the winter and spring. Influenza A(H1N1)pdm09 replaced the usual seasonal H1N1 virus during 2010-2012. Continuing epidemiological surveillance of influenza virus is important to monitor trends in influenza infections and to develop prevention and control measures.

[Financial burden of hepatitis B-related diseases and factors influencing the costs in Shenzhen, China].

OBJECTIVE: To investigate the direct, indirect and intangible costs due to hepatitis B-related diseases and to explore main factors associated with the costs in Shenzhen. METHODS: Cluster sampling for cases collected consecutively during the study period was administrated. Subjects were selected from eligible hepatitis B-related patients. By pre-trained professional investigators, health economics-related information was collected, using a structured questionnaire. Hospitalization expenses were obtained through hospital records after the patients were discharged from hospital. Total economic burden of hepatitis B-related patients would involve direct, indirect and intangible costs. Direct costs were further divided into direct medical costs and direct nonmedical costs. Human Capital Approach was employed to measure the indirect costs both on patients and the caregivers in 1-year time span. Willing to pay method was used to estimate the intangible costs. Multiple linear stepwise regression models were conducted to determine the factors linked to the economic burden. RESULTS: On average, the total annual cost of per patient with hepatitis B-related diseases was 81 590.23 RMB Yuan. Among which, direct, indirect and intangible costs were 30 914.79 Yuan (account for 37.9%), 15 258.01 Yuan (18.7%), 35 417.43 Yuan (43.4%), respectively. The total annual costs per patient for hepatocellular carcinoma, severe hepatitis B, decompensated cirrhosis, compensated cirrhosis, chronic hepatitis B and acute hepatitis B were 194 858.40 Yuan, 144 549.20 Yuan, 120 333.60 Yuan, 79 528.81 Yuan, 66 282.46 Yuan and 39 286.81 Yuan, respectively. The ratio of direct to indirect costs based on the base-case estimation foot add to 2.0:1, increased from hepato-cellular carcinoma (0.7:1) to compensated cirrhosis (3.5:1), followed by acute hepatitis B (3.3:1), severe hepatitis B (2.8:1), decompensate cirrhosis (2.3:1) and chronic hepatitis B (2.2:1). Direct medical costs were more than direct nonmedical. Ratio between the sum total was 16:1. The proportions of total annual cost per patient with hepatitis B-related diseases accounted for annual patient income were 285.3%, and 75.4% for annual household income. Furthermore, proportions of direct costs accounted for annual patient income and annual household income were 108.1% and 28.6%. The total annual indirect cost per person was 8123.38 Yuan for patients of all hepatitis B-related diseases, while 7134.63 Yuan for caregivers. Corresponding work-loss days were 55.74 days for patients and 19.83 days for caregivers. Based on multiple linear stepwise regression analysis, age of patients was a common influencing factor to all kinds of costs. Other factors were as follows: complicated with other diseases, antiviral medication, monthly household income and self-medications. CONCLUSION: The economic burden of hepatitis B-related diseases was substantial for patients and their families. All costs tended to increase with the severity of disease. The direct costs were larger than the indirect costs. And the direct medical costs were more than the direct ones. Indirect costs based on patients were larger than the ones of caregivers.

[Assessment of the young rat model of visceral hypersensitivity by measuring electrical discharge of external oblique].

OBJECTIVE: To study the value of measuring electrical discharge of external oblique in assessment of young rat model of visceral hypersensitivity. METHODS: Eight-day-old neonatal Sprague-Dawley rats were randomly assigned to two groups: an experimental group and a control group (n=16 each). Rats in the experimental group were subjected to mechanical colorectal irritation daily for 7 consecutive days, while the rats in the control group did not received colorectal irritation treatment. On the 6th week of their lives, the spike amplitude of external oblique were measured to evaluate the bowel sensitivity. RESULTS: When the colorectal distention (CRD) pressure was 30 and 45 mmHg, the 95% confidence interval of the spike amplitude in the experimental group was significantly higher than that in the control group (P<0.01). When the CRD pressure were 60 and 75 mmHg, the 95% confidence interval of the spike amplitude in female rats was significantly higher than that in males (P<0.05). CONCLUSIONS: The electrical discharge of external oblique confirmed that chronic colorectal irritation in neonatal rats can result in a chronic visceral hypersensitivity in the juvenile stage, with gender differences. Electrophysiological assessment is a quantitative test, and can objectively reflect visceral sensibility of pain.