CD36 accelerates the progression of hepatocellular carcinoma by promoting FAs absorption.

CD36 is emerging as a potential strategy for cancer treatment because of its function of regulating fatty acid intake. The purpose of this study was to clarify the molecular mechanism of CD36 in the progression of HCC. TCGA database was used to analyze the relationship of CD36 with HCC. The expression of CD36 in HCC clinical samples and cell lines was detected by qRT-PCR and western blot. Huh7 cells and HCCLM3 cells were transfected and treated into different group. CCK-8 and clone formation assay were used to detect the cell proliferation ability. Wound healing and transwell experiment were used to detect the metastatic ability. HCC xenografts were constructed in nude mice by subcutaneous injection of stably transfected Huh7 cells. The expression of CD36 in HCC was detected by immunohistochemistry (IHC). The contents of phospholipids and triglycerides in HCC cells were detected by ELISA. And the content of neutral lipids in HCC cells was detected by staining with BODIPY 493/503 and DAPI dye. Then transcriptional sequencing was used to determine the downstream mechanism of CD36 in HCC, and the differentially expressed genes (DEGs) were analyzed. CD36 was upregulated in HCC. Knockdown of CD36 could suppress the proliferation and metastasis of HCC in vitro and in vivo by regulating FAs intake in HCC. In addition, the expression of AKR1C2 was suppressed by sh-CD36, and which was also involved in the regulation of FAs intake. The molecular mechanism by which CD36 accelerated the progression of HCC was to promote the expression of AKR1C2 and thus enhance fatty acids (FAs) intake.

Zwitterionic Polypeptoids: A Promising Class of Antifouling Bioinspired Materials.

Biofouling caused by protein adsorption and microbial colonization remains a great challenge in many applications. In this work, we synthesized a new type of zwitterionic polypeptoid containing carboxybetaine (CB) moieties (PeptoidCB) through thiol-ene chemistry of poly(N-allylglycine) (PNAG). The zwitterionic antifouling hydrogel was subsequently prepared by co-mixing PeptoidCB with agarose, which exhibited excellent resistance to non-specific protein adsorption and bacterial adhesion. Further, PeptoidCB-modified block copolypeptoids with amphiphilic structure were synthesized to form nanoparticles in an aqueous solution with neglected protein adsorption. The ability of PeptoidCB to resist non-specific protein adsorption and bacterial adhesion makes it a promising candidate for biomedical and industrial applications.

Hierarchical Approach for Controlled Assembly of Branched Nanostructures from One Polymer Compound by Engineering Crystalline Domains.

The interplay of crystalline packing, which governs atomic length-scale order, and hierarchical assembly, which governs longer length scales, is essential to fabricate complex superstructures from polymers for many applications. Here, we demonstrate that a diblock copolymer containing an N-octylglycine peptoid block, which has a propensity to crystallize, can form distinct hierarchical superstructures including a star-like morphology, a superbrush, or a nanosheet by tuning the balance between surface energy arising from the solubility of the copolymers and crystallization energy of the solvophobic polypeptoid blocks. We show that partially ordered micellar aggregates (clusters) are key intermediates that form early in the assembly process and template the formation of superstructures via the oriented fusion of individual micelles as the growth materials. Notably, the fiber-like branch of the superstructures is driven by crystallization and exhibits growth in a living linear manner. The superstructures can be internalized by mammalian cells and hold promise for biomedical applications.

Polypeptoid-Assisted Formation of Supramolecular Architectures from Folic Acid for Targeted Cancer Therapy with Enhanced Efficacy.

In recent years, much research has focused on assemblies formed by charged polyelectrolytes via electrostatic interactions in aqueous solutions as they have the potential to be used in a variety of biomedical applications. In this study, we analyzed supramolecular architectures fabricated from poly(N-allyl glycine) modified with cysteamine (PNAG-NH2) and folic acid (FA) via electrostatic interactions. The PNAG-NH2/FA complex exhibits a reversible pH-responsive morphological transformation from vesicles (pH = 7.0) to nanofibers (pH = 5.0). Besides, we demonstrated that homopolypeptoids electrostatically interact with FA, thereby facilitating ribbon- and disk-like H-bonded FA patterns and inducing the formation of vesicle nanostructures and fiber arrays, respectively. Additionally, we systematically studied the influence of the degree of polymerization of the polymers, concentration, charge mixing ratio, and type of the polymer and the small-molecule acid on the assemblies. We show the superior stability of the polypeptoid/FA complex as compared to those based on other polymers. We established that the polypeptoid/FA complex exhibits a superior stability than those based on other polymers. By applying these beneficial properties, we encapsulated the anticancer drug doxorubicin (DOX) in the complex vesicle to obtain a pH-induced drug carrier. Cytotoxicity studies and internalization assays revealed that the DOX-loaded PNAG-NH2/FA complex vesicles display an enhanced therapeutic efficacy via typical FA-folate receptor-mediated endocytosis in vitro.

The Ser326Cys polymorphism of hOGG1 is associated with intrahepatic cholangiocarcinoma susceptibility in a Chinese population.

OBJECTIVE: Intrahepatic cholangiocarcinoma is a rare disease whose etiology is far from clear, the Ser326Cys polymorphism in human 8-hydroxyguanine glycosylase (hOGG1) has been shown associated with various cancers, however, the association of Ser326Cys (rsl052133) polymorphism and intrahepatic cholangiocarcinoma susceptibility has not been clarified. The purpose of this study is to investigate whether this polymorphism is related to the genetic susceptibility of intrahepatic cholangiocarcinoma. METHODS: A total 150 patients and 150 normal people were included in this study, the Ser326Cys polymorphisms in each group were genotyped using PCR-RFLP method. RESULTS: We found that individuals carrying Cys/Cys genotype were exposed to higher riskof intrahepatic cholangiocarcinoma (OR=2.924, 95% CI=1.475-5.780) compared with the individuals with wild type genotype Ser/Ser. Further analysis revealed that male individuals carrying Cys/Cys genotype also had increased risk (OR=2.762, 95% CI=1.233-6.173), whereas no significant difference was observed in female group. CONCLUSIONS: Therefore, our data indicates that the Ser326Cys (rs1052133) polymorphism is associated with intrahepatic cholangiocarcinoma susceptibility, and it shows preference in male population.

Correlation between B7-H3 expression and matrix metalloproteinases 2 expression in pancreatic cancer.

BACKGROUND: B7-H3 and matrix metalloproteinases 2 (MMP-2) are reported highly expressed in malignant tumor, we investigate the relationship between B7-H3 expression and MMP-2 on malignant behavior and prognosis predictable value in pancreatic cancer. METHODS: We tested the expressions of B7-H3 and MMP-2 protein in 45 pancreatic surgical resected cancer samples; meanwhile, the clinicopathological data of enrolled patients were obtained for correlation analysis to obtain their relationship with pancreatic cancer progress. RESULTS: The expression of B7-H3 was up-regulated with infiltrating depth, lymph node metastasis and TNM stage (P < 0.01). Positive expression rate of MMP-2 in pancreatic cancer tissues was 44.35%, whereas negative in normal pancreatic tissues. Multivariate analysis of Logistic regression showed B7-H3 and MMP-2 expressions were hazardous makers correlated with infiltrating depth (P < 0.05). CONCLUSION: Our study showed combined detections of B7-H3 and MMP2 protein expression could identify patients at high risk in disease recurrence and prognosis more efficiently.

The preliminary experience in simultaneous treatment of rectal cancer and synchronous liver metastases with laparoscopy.

BACKGROUND/AIMS: There is no consensus for laparoscopy first in patients with rectal cancer and synchronous liver metastases, whose metastases are confined to the liver. This study aimed to evaluate its indications for one-stage surgery in laparoscopy. MATERIALS AND METHODS: Eighteen patients with rectal cancer and synchronous liver metastases, who had undergone laparoscopic colorectal resection and simultaneous treatment for liver metastases, were retrospectively reviewed. RESULTS: Concomitant with laparoscopic colorectal resection, eight patients received liver resection simultaneously; 10 patients underwent a variety of down-staging management including local ablation, right hepatic portal vein ligation, and implantation of chemotherapy pumps into the hepatic artery. The colo-anal/rectal anastomoses were performed with a stapler or "pull-though" mode though the anus. Three patients underwent two-stage liver resection following tumor down-staging. Median survival time was 22.3 months. CONCLUSIONS: Laparoscopy approach for rectal cancer and synchronous liver metastases is feasible in selected patients. Colon pull-through anastomosis was a potential method to avoid abdominal incision and decrease the risk of anastomotic leakage. It is worth further investigation regarding its advantages over traditional modalities with a prospective randomized controlled study.

Laparoscopic spleen-preserving distal pancreatectomy (LSPDP).

BACKGROUND/AIMS: To study the feasibility and safety of laparoscopic spleen-preserving distal pancreatectomy (LSPDP). METHODOLOGY: Four patients underwent attempted LSPDP from February 2008 to April 2010 in our department and their clinical data and outcome were reviewed retrospectively. RESULTS: A total of 4 laparoscopic distal pancreas resections were attempted for 3 female and 1 male patient. All of these operations were successful with an average operative time of 235 min (range 115-305 min) and average blood loss of 200mL (range 100-450mL). The mean hospital stay time was 12.8 days, ranging from 10 to 21 days. Pancreatic fistula occurred in 1 patient then cured by extending drainage. Postoperative pathological examination showed those 2 cases of serous cystadenoma, 1 case of mucinous cystadenoma and 1 case of insulinoma, respectively. CONCLUSIONS: LSPDP is minimally invasive, safe and feasible for the management of benign pancreatic tail tumors with the advantages of earlier recovery and less morbidity from complications.

Perioperative analysis of laparoscopic liver resection with different methods of hepatic inflow occlusion.

BACKGROUND: During liver resection, bleeding remains the most important challenge. A reduction in blood loss and avoiding the need for a blood transfusion are important objectives for liver surgeons today. The authors compared the intra- and postoperative course of patients undergoing laparoscopic liver resections under intermittent total pedicle occlusion (IPO), hemihepatic vascular occlusion (HVO), and selective vascular occlusion (SVO). SUBJECTS AND METHODS: Retrospective analysis was conducted of patient data from 41 cases of laparoscopic liver resection in three groups of patients under different occlusion methods, including 15 cases of IPO, 15 cases of HVO, and 11 cases of SVO. The advantages and disadvantages of the various methods were compared, as well as blood loss, operation time, changes in postoperative liver function, and complications. RESULTS: There was no operative death in any of the 41 patients. Generally, there was no significant difference among the three groups in blood loss, clamping time, or operative time. After the operation, the effect on liver function for the HVO and SVO groups was significantly less severe than that for the IPO group (P<.05). The incidence of postoperative complications was mainly related to IPO and the larger amount of bleeding. CONCLUSIONS: Both HVO and SVO are feasible in laparoscopic hepatectomy and have the advantage of reducing liver remnant ischemia injury and modality rate over IPO. HVO is easy to do for left lateral lobe or resection of the left half of the liver. SVO is suitable for right lobe resection.

Short-term outcomes from a multicenter retrospective study in China comparing laparoscopic and open surgery for the treatment of infected pancreatic necrosis.

BACKGROUND: Laparoscopic surgery for confirmed infected pancreatic necrosis (IPN) represents a relatively new solution. There are no studies comparing the outcomes of laparoscopic and open surgery for patients with IPN. The aims of this study were to investigate the feasibility of laparoscopic management for patients with IPN and to compare the outcomes of laparoscopic and open surgery. METHODS: Seventy-six patients with IPN who underwent open surgery (Open-group) or laparoscopic surgery (Lap-group) were retrospectively reviewed. Demographic data, white blood cell count, and APACHE II score upon admission, operative findings, major complications, and mortality were compared between the Open-group and the Lap-group. The Lap-group was further divided into two subgroups (early and late), and the operative difficulty was compared between the two subgroups. RESULTS: There were no significant differences between the Open-group and the Lap-group with respect to demographic data, white blood cell count, and APACHE II score. Although the mean operative time was significantly shorter in the Open-group than in the Lap-group, the estimated blood loss was significantly greater in the Open-group than in the Lap-group, as was the rate of complications. The mean postoperative hospital stay in the Open-group was significant longer than in the Lap-group, too. In the Lap-group, the mean operating time, estimated blood loss, and conversion rate in the early subgroup were significantly lower than in the late subgroup. CONCLUSION: Laparoscopic necrosectomy and the placement of an intermittent irrigation and continuous suction drainage system for IPN is feasible, effective, and of minimal invasiveness. The late laparoscopic necrosectomy is relatively difficult.