Downregulation of GNAI3 Promotes the Pathogenesis of Methionine/Choline-Deficient Diet-Induced Nonalcoholic Fatty Liver Disease

Background/Aims: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) has not be fully elucidated, and the lack of therapeutic strategies for NAFLD is an urgent health problem. Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 (GNAI3) participates in several biological processes, but its relationship with lipid metabolism and NAFLD has not yet been reported. We aimed to determine the function of GNAI3 in the development of NAFLD. Methods: Mice were fed a methionine and choline-deficient diet to induce NAFLD. An NAFLD model in HepG2 cells was induced by free fatty acid treatment. GNAI3 levels in HepG2 cells were downregulated by shRNA. Protein levels of related proteins were evaluated by Western blotting, and mRNA levels were determined by quantitative reverse transcription polymerase chain reaction. Hematoxylin and eosin and Oil Red O staining were used to observe histological changes in liver tissue. Results: The dysregulated hepatic lipid metabolism in the NAFLD mouse model was enhanced by GNAI3 knockout, which also provoked worse liver damage. In the NAFLD model in HepG2 cells, the downregulation of GNAI3 promoted cellular lipid accumulation and enhanced the changes in lipid metabolic enzyme levels. Conclusions: This study demonstrates that GNAI3 participates in the development of NAFLD in both cellular and mouse models. The data indicate that GNAI3 is a potential new target for the treatment of NAFLD in humans

Progress of Inertial Microfluidics in Principle and Application

Inertial microfluidics has become a popular topic in microfluidics research for its good performance in particle manipulation and its advantages of simple structure, high throughput, and freedom from an external field. Compared with traditional microfluidic devices, the flow field in inertial microfluidics is between Stokes state and turbulence, whereas the flow is still regarded as laminar. However, many mechanical effects induced by the inertial effect are difficult to observe in traditional microfluidics, making particle motion analysis in inertial microfluidics more complicated. In recent years, the inertial migration effect in straight and curved channels has been explored theoretically and experimentally to realize on-chip manipulation with extensive applications from the ordinary manipulation of particles to biochemical analysis. In this review, the latest theoretical achievements and force analyses of inertial microfluidics and its development process are introduced, and its applications in circulating tumor cells, exosomes, DNA, and other biological particles are summarized. Finally, the future development of inertial microfluidics is discussed. Owing to its special advantages in particle manipulation, inertial microfluidics will play a more important role in integrated biochips and biomolecule analysis

Selective Radical Resection for Unresectable Pancreatic Cancer

Background and Objective: &nbsp;For inefficiency of chemotherapy and radiation against pancreatic cancer, resection rate for primary unresectable pancreatic cancer remains very low. This study was carried out to evaluate the safety and value of radical resection for unresectable pancreatic cancer (UPC). Methods: &nbsp;Clinical data were analyzed retrospectively. In unresectable group, 360&deg; resection of the involved artery sheath, resection and reconstruction of the involved artery, resection and reconstruction of the involved vein as well as resection and reconstruction of combined organs were performed. Operation time, intraoperative blood loss, ICU transitional treatment, pancreatic fistula, bleeding, reoperation and survival time were analyzed for two groups. Results: &nbsp;Operation time and intraoperative blood loss were greatly increased in the unresectable group. The incidence of intractable diarrhea and abdominal hemorrhage in the unresectable group were higher. However, the rate of ICU transitional therapy, delayed gastric emptying and reoperation were lower. Grade-C pancreatic fistula occurred in neither group. Conclusion: &nbsp;Surgical treatment through stringent selection for patients with unresectable pancreatic cancer is a safer technique and median post-operative survival time is similar to patients with resectable pancreatic cancer.</p

Arterial reconstruction by anastomosis of left gastric artery and superior mesenteric artery for locally advanced pancreatic carcinoma

We report the case of a 61-year-old man with pancreatectomy with arterial resection and reconstruction and extended lymph node dissection because of locally advanced pancreatic cancer. Surgery revealed the tumor invading the root part of the superior mesenteric artery, so we cut off and reconstructed the artery root through end-to-end anastomosis of the left gastric artery and superior mesenteric artery. The left gastric artery is a reasonable choice to reconstruct the superior mesenteric artery, and to the best of our knowledge, only a few reports describe locally advanced pancreatic cancer as an indication for our surgical procedure

CD44V3, an Alternatively Spliced Form of CD44, Promotes Pancreatic Cancer Progression

Pancreatic cancer is one of the most lethal malignant tumors. However, the molecular mechanisms responsible for its progression are little known. This study aimed to understand the regulatory role of CD44V3 in pancreatic cancer. A Kaplan&ndash;Meier analysis was performed to reveal the correlation between CD44/CD44V3 expression and the prognosis of pancreatic cancer patients. CD44V3 and U2AF1 were knocked down using shRNAs. The proliferation, migration, invasion, and stemness of two pancreatic cell lines, BxPC-3 and AsPC-1, were examined. The expression of CD44V3, cancer-associated markers, and the activation of AKT signaling were detected by qRT-PCR and Western blot. Both CD44 and CD44V3 expression levels were associated with a poor prognosis in pancreatic cancer patients. Interestingly, the expression of CD44V3, instead of CD44, was greatly increased in tumor tissues. CD44V3 knockdown inhibited the proliferation, migration, invasion, and stemness of cancer cells. CD44V3 splicing was regulated by U2AF1 and downregulation of U2AF1 enhanced CD44V3 expression, which promoted pancreatic cancer progression. CD44V3 is an important cancer-promoting factor, which may serve as a potential candidate for pancreatic cancer intervention

Downregulation of PRAME Suppresses Proliferation and Promotes Apoptosis in Hepatocellular Carcinoma Through the Activation of P53 Mediated Pathway

Background/Aims: The expression of PRAME and its role in hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to examine the functional role of PRAME in HCC development and exploring the molecular mechanism. Methods: We first detected PRAME expression in 96 human HCC tissue samples and correlated with clinicopathological characteristics and prognosis of the patients. We then established stable HCC cell lines with PRAME overexpression and knockdown followed by functional analysis in vitro. Further, we examined the relationship between PRAME and p53 pathway in vitro by using Western blotting. Finally, PRAME expression was detected to evaluate its correlation with p-p53 and p53 pathway related apoptotic proteins in xenograft tumor mouse model using immunohistochemistry. Results: PRAME expression was significantly higher in HCC tissues than in adjacent non-tumor tissues and their expression was positively correlated with alpha fetoprotein levels and tumor size. In addition, PRAME expression was associated with AJCC stage and is a potential biomarker of poor prognosis regarding 5-year overall survival in HCC. In vitro studies, we found that PRAME expression was higher in HCC cell lines than in normal hepatic cell line. Inhibited cell proliferation and increased cell apoptosis was observed in PRAME knockdown HCC cells. Futher, increased cell apoptosis was correlated with the proportion of cells in G0/G1 stage, activated p53 mediated apoptosis, and increased cyclin p21 expression. Xenograft analysis in nude mice also found that PRAME knockdown inhibited tumorigenesis while PRAME overexpression had opposite effect. Conclusions: In HCC, PRAME serves as a potential biomarker for poor prognosis and novel therapeutic target in treating this cancer. PRAME is a potential biomarker of poor prognosis in HCC. PRAME surpresses HCC cell death in vitro and in vivo by regulating p53 apoptotic signaling and may serve as a potential therapeutic target in HCC