miR-663a inhibits tumor growth and invasion by regulating TGF-ß1 in hepatocellular carcinoma.

BACKGROUND: The dysregulation of miR-663a is frequently observed in many human cancers. However, the functional role and precise mechanism of miR-663a have been controversial in hepatocellular carcinoma (HCC) and need to be studied in depth. METHODS: The expression of miR-663a was detected in human cell lines and HCC tissues by quantitative RT-PCR (qRT-PCR), and data from the Cancer Genome Atlas (TCGA). Cell proliferation was investigated using MTS, EdU, colony formation assays, and xenograft animal experiments, and the cell invasion capacity was evaluated using the transwell assay. The target gene of miR-663a was identified by qRT-PCR, Western blot, and dual-luciferase reporter assays. The clinicopathological features of miR-663a and the correlation between miR-663a and TGF-ß1 expression were also investigated in the clinical samples of HCC. RESULTS: miR-663a was significantly downregulated in HCC cells relative to immortal normal liver cells, as indicated using qRT-PCR, and the lower expression of miR-663a was also confirmed in HCC tissue samples and the data from TCGA. The expression of miR-663a in HCC tissue samples was statistically significantly associated with size and the number of tumors. In addition, the upregulation of miR-663a inhibited the proliferation and invasion of HCC cells in vitro. Further study showed that miR-663a directly targeted transforming growth factor beta 1 (TGF-ß1) to suppress HCC invasion, and that the inhibitory effect of miR-663a on cell invasion could be regulated by TGF-ß1. In vivo studies showed that miR-663a significantly inhibited tumor growth. A negative correlation between miR-663a and TGF-ß1 expression was also confirmed from the clinical samples of HCC. CONCLUSIONS: miR-663a acts as a tumor suppressor and exerts a substantial role in inhibiting the proliferation, invasion, and tumorigenesis of HCC by regulating TGF-ß1 in vitro and in vivo. These observations indicate that miR-663a may be a suitable diagnostic, therapeutic, and prognostic target for the treatment of HCC.

Basiliximab application on liver recipients: a meta-analysis of randomized controlled trials.

BACKGROUND: The benefits of the application of basiliximab induction therapy in liver transplantation are not clear. The present meta-analysis was to evaluate the pros and cons of basiliximab use in liver transplantation. DATA SOURCES: We searched the associated publications in English from July 1998 to December 2015 in the following databases: MEDLINE, PubMed, Ovid, EMBASE, Web of Science and Cochrane Library. RESULTS: Basiliximab significantly decreased the incidence of de novo diabetes mellitus after liver transplantation (RR=0.56; 95% CI: 0.34-0.91; P=0.02). Subgroup analysis showed that basiliximab in combination with steroids-free immunosuppressant significantly decreased the incidence of biopsy-proven acute rejection (RR=0.62; 95% CI: 0.39-0.97; P=0.04) and new-onset hypertension (RR=0.62; 95% CI: 0.42-0.93; P=0.02). CONCLUSIONS: Basiliximab may be effective in reducing de novo diabetes mellitus. What is more, basiliximab in combination with steroids-free immunosuppressant shows statistical benefit to reduce biopsy-proven acute rejection and de novo hypertension.

ZnSe-material phase mask applied to athermalization of infrared imaging systems.

This paper reports a ZnSe-material phase mask that is applied to athermalization of a conventional infrared imaging system. Its principle, design, manufacture, measurement, and performance validation are successively discussed. This paper concludes that a ZnSe-material phase mask has a permissible manufacturing error 2.14 times as large as a Ge-material phase mask. By constructing and solving an optimization problem, the ZnSe-material phase mask is optimally designed. The optimal phase mask is manufactured and measured with a form manufacturing error of 1.370 µm and a surface roughness value of 9.926 nm. Experiments prove that the wavefront coding athermalized longwave infrared (LWIR) imaging system works well over the temperature range from -40°C to +60°C.

Is radiofrequency ablation equal to surgical re-resection for recurrent hepatocellular carcinoma meeting the Milan criteria? A meta-analysis.

PURPOSE: To evaluate the clinical efficacy and safety of radiofrequency ablation (RFA) with surgical re-resection (SRR) in patients with postoperative recurrent hepatocellular carcinoma (RHCC) meeting the Milan criteria. METHODS: A literature search was performed to identify comparative studies addressing outcomes of both RFA and SRR for RHCC meeting the Milan criteria. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using either the fixed effects model or the random effects model. RESULTS: Five nonrandomized controlled trials were included in the analysis. These studies included a total of 543 patients: 243 treated with RFA and 300 treated with SRR. The SRR group had a better 3-year recurrence-free survival rate compared with RFA group (OR 0.44, 95%CI 0.25-0.77, p=0.004). However, there were no obvious differences between RFA and SRR group in overall survival (OS) rates, re-recurrence rate and OS rates with tumors ≤ 3cm. What's more, the RFA group had a safety advantage with less complications of Clavien classification grade II or higher compared with SRR group (OR 0.21, 95%CI 0.05-0.94, p=0.04). CONCLUSIONS: RFA seemed to be superior to SRR in the treatment of patients with RHCC meeting the Milan criteria on account of clinical safety. However, these findings have to be carefully interpreted due to the lower level of evidence.

Dynamic three-dimensional liver volume assessment of liver regeneration in hilar cholangiocarcinoma patients undergoing hemi-hepatectomy.

Background: For patients with hilar cholangiocarcinoma (HC) undergoing hemi-hepatectomy, there are controversies regarding the requirement of, indications for, and timing of preoperative biliary drainage (PBD). Dynamic three-dimensional volume reconstruction could effectively evaluate the regeneration of liver after surgery, which may provide assistance for exploring indications for PBD and optimal preoperative bilirubin value. The purpose of this study was to explore the indications for PBD and the optimal preoperative bilirubin value to improve prognosis for HC patients undergoing hemi-hepatectomy. Methods: We retrospectively analyzed the data of HC patients who underwent hemi-hepatectomy in the First Affiliated Hospital of China Medical University from 2012 to 2023. The liver regeneration rate was calculated using three-dimensional volume reconstruction. We analyzed the factors affecting the liver regeneration rate and occurrence of postoperative liver insufficiency. Results: This study involved 83 patients with HC, which were divided into PBD group (n=36) and non-PBD group (n=47). The preoperative bilirubin level may be an independent risk factor affecting the liver regeneration rate (P=0.014) and postoperative liver insufficiency (P=0.016, odds ratio=1.016, ß=0.016, 95% CI=1.003-1.029). For patients whose initial bilirubin level was >200 µmol/L (n=45), PBD resulted in better liver regeneration in the early stage (P=0.006) and reduced the incidence of postoperative liver insufficiency [P=0.012, odds ratio=0.144, 95% confidence interval (CI)=0.031-0.657]. The cut-off value of bilirubin was 103.15 µmol/L based on the liver regeneration rate. Patients with a preoperative bilirubin level of ≤103.15 µmol/L shown a better liver regeneration (P<0.01) and lower incidence of postoperative hepatic insufficiency (P=0.011, odds ratio=0.067, 95% CI=0.008-0.537). Conclusion: For HC patients undergoing hemi-hepatectomy whose initial bilirubin level is >200 µmol/L, PBD may result in better liver regeneration and reduce the incidence of postoperative liver insufficiency. Preoperative bilirubin levels ≤103.15 µmol/L maybe recommended for leading to a better liver regeneration and lower incidence of postoperative hepatic insufficiency.

Advances in electroactive biomaterials: Through the lens of electrical stimulation promoting bone regeneration strategy.

The regenerative capacity of bone is indispensable for growth, given that accidental injury is almost inevitable. Bone regenerative capacity is relevant for the aging population globally and for the repair of large bone defects after osteotomy (e.g., following removal of malignant bone tumours). Among the many therapeutic modalities proposed to bone regeneration, electrical stimulation has attracted significant attention owing to its economic convenience and exceptional curative effects, and various electroactive biomaterials have emerged. This review summarizes the current knowledge and progress regarding electrical stimulation strategies for improving bone repair. Such strategies range from traditional methods of delivering electrical stimulation via electroconductive materials using external power sources to self-powered biomaterials, such as piezoelectric materials and nanogenerators. Electrical stimulation and osteogenesis are related via bone piezoelectricity. This review examines cell behaviour and the potential mechanisms of electrostimulation via electroactive biomaterials in bone healing, aiming to provide new insights regarding the mechanisms of bone regeneration using electroactive biomaterials. The translational potential of this article: This review examines the roles of electroactive biomaterials in rehabilitating the electrical microenvironment to facilitate bone regeneration, addressing current progress in electrical biomaterials and the mechanisms whereby electrical cues mediate bone regeneration. Interactions between osteogenesis-related cells and electroactive biomaterials are summarized, leading to proposals regarding the use of electrical stimulation-based therapies to accelerate bone healing.

RPL35A promotes the progression of cholangiocarcinoma by mediating HSPA8 ubiquitination.

BACKGROUND: Cholangiocarcinoma (CCA) is a biliary epithelial malignant tumor with an increasing incidence worldwide. Therefore, further understanding of the molecular mechanisms of CCA progression is required to identify new therapeutic targets. METHODS: The expression of RPL35A in CCA and para-carcinoma tissues was detected by immunohistochemical staining. IP-MS combined with Co-IP identified downstream proteins regulated by RPL35A. Western blot and Co-IP of CHX or MG-132 treated CCA cells were used to verify the regulation of HSPA8 protein by RPL35A. Cell experiments and subcutaneous tumorigenesis experiments in nude mice were performed to evaluate the effects of RPL35A and HSPA8 on the proliferation, apoptosis, cell cycle, migration of CCA cells and tumor growth in vivo. RESULTS: RPL35A was significantly upregulated in CCA tissues and cells. RPL35A knockdown inhibited the proliferation and migration of HCCC-9810 and HUCCT1 cells, induced apoptosis, and arrested the cell cycle in G1 phase. HSPA8 was a downstream protein of RPL35A and overexpressed in CCA. RPL35A knockdown impaired HSPA8 protein stability and increased HSPA8 protein ubiquitination levels. RPL35A overexpression promoted CCA cell proliferation and migration. HSPA8 knockdown inhibited CCA cell proliferation and migration, and reversed the promoting effect of RPL35A. Furthermore, RPL35A promoted tumor growth in vivo. In contrast, HSPA8 knockdown suppressed tumor growth, while was able to restore the effects of RPL35A overexpression. CONCLUSION: RPL35A was upregulated in CCA tissues and promoted the progression of CCA by mediating HSPA8 ubiquitination.

Characterizing ligand-receptor interactions and unveiling the pro-tumorigenic role of CCL16-CCR1 axis in the microenvironment of hepatocellular carcinoma.

Background: The heterogeneity of the tumor microenvironment significantly influences the prognosis of hepatocellular carcinoma (HCC) patients, with cell communication through ligand-receptor complexes playing a central role. Methods: We conducted single-cell transcriptomic analysis on ten HCC tissues to identify ligand-receptor genes involved in malignant HCC cell communication using CellChat. Leveraging RNA-Seq data from the TCGA Liver Cancer (TCGA-LIHC) and Liver Cancer - RIKEN, JP (LIRI-JP) cohorts, we employed Cox regression analysis to screen for prognosis-related genes. Prognostic risk models were constructed through unsupervised clustering and differential gene expression analysis. Subsequently, a co-culture system involving tumor cells and macrophages was established. A series of experiments, including Transwell assays, immunofluorescence staining, immunoprecipitation, flow cytometry, and immunohistochemistry, were conducted to elucidate the mechanism through which HCC cells recruit macrophages via the CCL16-CCR1 axis. Results: Single-cell analysis unveiled significant interactions between malignant HCC cells and macrophages, identifying 76 related ligand-receptor genes. Patients were classified into three subtypes based on the expression patterns of eight prognosis-related ligand-receptor genes. The subtype with the worst prognosis exhibited reduced infiltration of T cell-related immune cells, downregulation of immune checkpoint genes, and increased M2-like tumor-associated macrophage scores. In vitro experiments confirmed the pivotal role of the CCL16-CCR1 axis in the recruitment and M2 polarization of tumor-associated macrophages. Clinical samples demonstrated a significant association between CCL16 protein expression levels and advanced stage, lymph node metastasis, and distant metastasis. Immunohistochemistry and immunofluorescence staining further confirmed the correlation between CCL16 and CCR1, CD68, and CD206, as well as CD68+CCR1+ macrophage infiltration. Conclusions: Our study identified molecular subtypes, a prognostic model, and immune microenvironment features based on ligand-receptor interactions in malignant HCC cell communication. Moreover, we revealed the pro-tumorigenic role of HCC cells in recruiting M2-like tumor-associated macrophages through the CCL16-CCR1 axis.

Survival benefit of perioperative locoregional adjuvant treatment for hepatocellular carcinoma with portal vein tumor thrombosis: A systematic review and Bayesian network meta-analysis.

BACKGROUND: To identify the optimal strategy for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) by comparing the oncological prognosis of different perioperative locoregional adjuvant treatments. METHODS: Electronic database were searched for relevant studies. Overall survival (OS) and recurrence-free survival (RFS) were pooled by pairwise and network meta-analysis. RESULTS: Fourteen eligible trials with 1927 patients and covering four adjuvant treatments were included. All adjuvant therapies in combination with surgery were shown to be superior to surgery alone. Adjuvant therapy with radiotherapy had the lowest hazard ratio (HR) for both OS (HR: 0.38, 95% CrI: 0.25-0.57) and RFS (HR: 0.27, 95% CrI: 0.11-0.65) compared with other combination treatments, with estimated surface under the cumulative ranking of 93.2% and 82.7%, respectively. CONCLUSIONS: Perioperative locoregional adjuvant therapy provides OS benefits and reduces the risk of recurrence for patients suffering from HCC with PVTT. Radiotherapy is likely to be the most effective adjuvant regimen.

A novel NiO/BaTiO3 heterojunction for piezocatalytic water purification under ultrasonic vibration.

This work designed and prepared a novel heterojunction composite NiO/BaTiO3 through a method of photodeposition and used it in piezocatalytic dye removal for the first time. Results of the piezocatalytic test indicated that the NiO/BaTiO3 composite presented superior efficiency and stability in the RhB degradation under the vibration of ultrasonic waves. The best NiO/BaTiO3 sample synthesized under light irradiation for 2 h displayed an RhB degradation rate of 2.41 h-1, which was 6.3 times faster than that of pure BaTiO3. By optimizing the piezocatalytic reaction conditions, the degradation rate constant of NiO/BaTiO3 can further reach 4.14 h-1 A variety of systematic characterizations were executed to determine the reason for the excellent piezocatalytic performance of NiO/BaTiO3. The band potentials of NiO and BaTiO3 are found to coincide, and at their contact interface, they may create a type-II p-n heterojunction structure. Driven by the potential difference and the built-in electric field, piezoelectrically enriched charge carriers can migrate between NiO and BaTiO3, resulting in improved efficiency in charge separation and an increase in the piezoelectric catalytic performance. This study may provide a potential composite catalyst and a promising idea for the design of highly efficient catalysts in the field of piezoelectric catalysis.

Development and Validation of a Preoperative Nomogram for Predicting Benign and Malignant Gallbladder Polypoid Lesions.

Purpose: The purpose of this study was to develop and validate a preoperative nomogram of differentiating benign and malignant gallbladder polypoid lesions (GPs) combining clinical and radiomics features. Methods: The clinical and imaging data of 195 GPs patients which were confirmed by pathology from April 2014 to May 2021 were reviewed. All patients were randomly divided into the training and testing cohorts. Radiomics features based on 3 sequences of contrast-enhanced computed tomography were extracted by the Pyradiomics package in python, and the nomogram further combined with clinical parameters was established by multiple logistic regression. The performance of the nomogram was evaluated by discrimination and calibration. Results: Among 195 GPs patients, 132 patients were pathologically benign, and 63 patients were malignant. To differentiate benign and malignant GPs, the combined model achieved an area under the curve (AUC) of 0.950 as compared to the radiomics model and clinical model with AUC of 0.929 and 0.925 in the training cohort, respectively. Further validation showed that the combined model contributes to better sensitivity and specificity in the training and testing cohorts by the same cutoff value, although the clinical model had an AUC of 0.943, which was higher than 0.942 of the combined model in the testing cohort. Conclusion: This study develops a nomogram based on the clinical and radiomics features for the highly effective differentiation and prediction of benign and malignant GPs before surgery.

Case report: Reconstruction of the left renal vein with resected autologous right renal vein interposition after excision of an inferior vena cava leiomyosarcoma.

Background: Leiomyosarcoma of the inferior vena cava (IVC) was a rather rare disease with the characteristics of invading the adjacent viscera. Surgical resection is the only potential curative treatment, and radiation therapy and chemotherapy for leiomyosarcoma are not definite. There is few literature reporting the leiomyosarcoma of the IVC. Case presentation: A previously healthy 64-year-old female was admitted to the First Affiliated Hospital of China Medical University with the complaint of right lower quadrant abdominal pain for almost three years and worsening with a radiating ache in the waist recently. Contrast-enhanced computed tomography(CT) scans revealed a large (7.8 cm*5.5 cm*5.0 cm) irregular hypodense retroperitoneal mass with heterogeneous enhancement and invasion of the IVC, and the right ureter was compressed with proximal ureteral dilatation and hydrops. Three-dimensional CT of the IVC revealed that the IVC was encircled by the tumor with moderate invasion. During the operation, the tumor was resected en bloc with the IVC (from the suprarenal to infrarenal segment), the right kidney with ureter, and the duodenum seromuscular layer. As the left renal vein was involved, it was also partly resected. IVC reconstruction was performed with the interposition of a 20 mm diameter polytetrafluoroethylene (PTFE) prosthesis, and the right renal vein was anastomosed between the left renal vein and the reconstructed IVC to guarantee the left renal vein reflux. The patient had an uneventful recovery process with normal renal function after the operation. However, follow-up CT indicated that the left renal vein was blocked two weeks after the surgery. The patient was discharged two weeks after the operation. She continues well and has no evidence of disease fourteen months after the surgery. Conclusions: Wide excision of the tumor en bloc with the IVC is the main treatment for leiomyosarcoma of the IVC. IVC reconstruction with prosthetic PTFE grafts is recommended. When the left renal vein is partly resected due to involvement of the tumor, reconstruction of left renal vein should also be performed to avoid renal impairment. If the right renal vein does not show tumor involvement, the resected right renal vein can be used to reconstruct the left renal vein.

Favorable response to multimodal treatment in hepatocellular carcinoma with inferior vena cava and right atrial tumor thrombus and left adrenal gland metastasis: A case report and literature review.

RATIONALE: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths and the sixth most commonly diagnosed cancer globally. Interdisciplinary and multimodal treatment strategies are essential for a successful therapy in HCC. Established therapies for HCC treatment include surgical resection, liver transplantation, local ablative therapies, transarterial chemoembolization (TACE), tyrosine kinase inhibitors (TKIs), immunotherapy, and radiotherapy (RT). PATIENT CONCERNS: A 52-year-old male patient did an ultrasound scan and found a large mass within the right lobe of the liver and gallstones in December 2018. He had a history of chronic hepatitis C virus infection (30 years) and was treated with sofosbuvir (400 mg, q.d.) for 1 year. The patient never had any symptoms of gallstones. Enhanced abdominal computed tomography of this patient showed a heterogeneous irregular mass with the largest measurement of up to 13.7 × 11.1 cm in size in the right lobe of the liver, meanwhile also had inferior vena cava (IVC) tumor thrombus, right atrial (RA) tumor thrombus, and left adrenal gland metastasis. The laboratory test data revealed that the serum tumor marker α-fetoprotein was 2.63 ng/mL, cancer antigen 19-9 (CA 19-9) was 34.40 U/mL, and protein induced by Vitamin K absence was 391.94 mAU/mL. DIAGNOSIS: HCC with IVC tumor thrombus, RA tumor thrombus, and left adrenal gland metastasis, and gallstones. INTERVENTIONS: He was hospitalized and received TACE treatment, oral TKIs, intravenous drip programmed cell death-1 (PD-1) inhibitor and RT. OUTCOMES: The patient showed a favorable response after consecutive treatment with TACE, TKIs, PD-1 inhibitor, and RT. Until now, the patient has survived 34 months since the diagnosis of the disease. LESSONS: Our case suggests that TACE combined with TKIs, PD-1 inhibitor, and RT may be a suitable treatment option for advanced HCC patients with IVC tumor thrombus and/or RA tumor thrombus, and/or adrenal gland metastasis.

A randomized controlled trial to compare the efficacy of regenerated and non-regenerated oxidized cellulose gauze for the secondary treatment of local bleeding in patients undergoing hepatic resection.

PURPOSE: Oxidized cellulose is available in many forms, but manufactured using either a regenerated or non-regenerated process. In this study, we evaluated the effects of 2 different hemostatic agents for the treatment of local bleeding in patients undergoing hepatic resection. METHODS: This was a monocentric, parallel-group, randomized, and controlled clinical trial to compare oxidized regenerated cellulose gauze (ORCG) with oxidized non-regenerated cellulose gauze (ONRCG) in patients undergoing hepatectomy. The primary endpoint was the time to hemostasis at the target bleeding site. The secondary endpoints were the postoperative drainage volume on the first 2 days after surgery and the hospital stay. RESULTS: There was no significant difference between the ORCG and ONRCG groups in time to hemostasis from column analysis (238.8 ± 121.6 seconds vs. 193.7 ± 85.3 seconds, P = 0.068), and there were no differences in the rates of hemostatic success between the 2 groups at 120 seconds (18.4% vs. 24.3%; odds ratio [OR], 0.703; 95% confidence interval [CI], 0.231-2.136) and 300 seconds (71.1% vs. 89.2%; OR, 0.298; 95% CI, 0.085-1.041). However, the ONRCG group was superior to the ORCG group in hemostasis according to the survival analysis (log-rank test, P = 0.044). Moreover, there were also no significant differences between the 2 groups in postoperative drainage volume on the first 2 days (P = 0.436, P = 0.381) and hospital stay (P = 0.537, P = 0.200). CONCLUSION: ONRCG was not inferior to ORCG as a hemostatic agent in patients undergoing liver resection.

Transcriptome changes for Nile tilapia (Oreochromis niloticus) in response to alkalinity stress.

Nile tilapia is an important economic fish in the world because of its fast growth, high meat yield and strong adaptability. It is more adaptable to high alkalinity than common freshwater fish and provides valuable material for developing alkaline-tolerant strains and understanding the adaptation mechanism of fish to extreme environmental stress. In this study, we employed high throughput RNA sequencing to reveal the tissues (gill, kidney and liver) transcriptome differences of O. niloticus at different carbonate alkalinities (FW, AW40 and AW60). A total of 1,369,381,790 raw reads were obtained, including 496,441,232 reads in FW group, 437,907,696 reads in AW40 and 435,032,862 reads in AW60. In addition, 484,555,626 reads in gill, 451,618,224 reads in kidney and 433,207,940 reads in liver. A large number of stress-regulated changes were detected comprehensively. We focused on 3 significantly change pathways (steroid biosynthesis, drug metabolism and protein digestion/absorption) and 17 DEGs (HMG-CoA reductase, UDP-glucuronosyltransferase, and carbonic anhydrase etc.) which were shared among compared groups (AW40 vs FW, AW60 vs FW, AW40 vs 60 AW60) in gill, kidney and liver, respectively. These pathways/genes are sensitive to alkalinity stress and crucial to the alkalinity adaptation of tilapia. Overall, we found a large number of candidate genes, which encode important regulators of stress tolerance and ultimately contribute to future alkaline-tolerant fish breeding. Among these genes, lipid metabolism (involving signal transduction), detoxification and immune related genes are more prominent to the response and adaptability of fish to alkalinity stress.

Change in Viability and Function of Pancreatic Islets after Coculture with Mesenchymal Stromal Cells: A Systemic Review and Meta-Analysis.

BACKGROUND: There is no clear consensus on the effect of coculture of islets with mesenchymal stem cells (MSCs) on islet function and viability. METHODS: We conducted a meta-analysis of relevant studies to evaluate the effect of coculture of islets with MSCs on the function and viability of islets, both in vitro and in vivo. We searched PubMed, Embase, and Web of Science databases for all relevant studies that compared the effect of coculture of islets with MSCs on the function and viability of islets (language of publication: English; reference period: January 2000-May 2019). Data pertaining to islet function and viability, concentrations of some cytokines, and in vivo experimental outcomes were extracted and compared. RESULTS: Twenty-four articles were included in the meta-analysis. In comparison to islets cultured alone, coculture of islets with MSCs was associated with a significantly higher islet viability [weighted mean difference (WMD), -15.59; -22.34 to -8.83; P < 0.00001], insulin level (WMD, -5.74; -9.29 to -2.19; P = 0.002), insulin secretion index (WMD, -2.45; -3.70 to -1.21; P = 0.0001), and higher concentrations of interleukin-6 (WMD, -1225.66; -2044.47 to -406.86; P = 0.003) and vascular endothelial growth factor (WMD, -1.19; -2.25 to -0.14; P = 0.03). Direct coculture of islets and MSCs significantly increased islet viability (WMD, -19.82; -26.56 to -13.07; P < 0.00001). In the in vivo experiments, coculture of islets with MSCs induced lower fasting blood glucose level (on postoperative days 21 and 28, WMD, 102.60; 27.14 to 178.05; P = 0.008 and WMD, 121.19; 49.56 to 192.82; P = 0.0009) and better glucose tolerance (blood glucose at 30 minutes after intraperitoneal injection of glucose, WMD, 85.92; 5.33 to 166.51; P = 0.04). CONCLUSION: Coculture of islets with MSCs improves insulin secretory function of islets and enhances islet viability. Direct coculture of two cells significantly increased islet viability. MSC-based strategy may be beneficial for clinical islet transplantation for type 1 diabetes in the future.

Amniotic Membrane Extract Protects Islets From Serum-Deprivation Induced Impairments and Improves Islet Transplantation Outcome.

Islet culture prior to transplantation is a standard practice in many transplantation centers. Nevertheless, the abundant islet mass loss and function impairment during this serum-deprivation culture period restrain the success of islet transplantation. In the present study, we used a natural biomaterial derived product, amniotic membrane extract (AME), as medium supplementation of islet pretransplant cultivation to investigate its protective effect on islet survival and function and its underlying mechanisms, as well as the engraftment outcome of islets following AME treatment. Results showed that AME supplementation improved islet viability and function, and decreased islet apoptosis and islet loss during serum-deprived culture. This was associated with the increased phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway. Moreover, transplantation of serum-deprivation stressed islets that were pre-treated with AME into diabetic mice revealed better blood glucose control and improved islet graft survival. In conclusion, AME could improve islet survival and function in vivo and in vitro, and was at least partially through increasing phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway.

A Novel Pentapeptide Inhibitor Reduces Amyloid Deposit Formation by Direct Interaction with hIAPP.

BACKGROUNDS: The presence of amyloid deposits of human islet amyloid polypeptide (hIAPP) in islet ß-cells has been associated with type 2 diabetes occurrence and islet graft failure. Self-assembly into oligomers and fibrils during the process of aggregation by hIAPP can lead to failure and depletion of ß-cells. Studies have shown that some critical regions of hIAPP might contribute to the aggregation. Thus, many studies focused on finding the effective molecules, especially the short-peptide inhibitors, that bind to these regions and disrupt the aggregation of hIAPP. In the present study, a novel pentapeptide inhibitor Phe-Leu-Pro-Asn-Phe (FLPNF) was designed and its effectiveness on the inhibition of the formation of amyloid deposits was examined. METHODS: The binding mode between FLPNF and hIAPP was performed using molecular docking. The effectiveness of FLPNF on inhibiting hIAPP amyloid aggregation was tested by Thioflavin T (ThT) staining. Furthermore, negative stain electron microscopy was used to observe hIAPP fibrils. A biolayer interferometry analysis was used to identify the interaction between FLPNF and hIAPP. In addition, the cytotoxicity toward INS-1 cells was tested by a cell proliferation assay. RESULTS: FLPNF was predicted to have a compact conformation to bind at the site of hIAPP. FLPNF strongly inhibited the amyloid aggregation of hIAPP at a 10 : 1 molar ratio in vitro. Coincubation of FLPNF with hIAPP decreased the amount of hIAPP fibrils. Furthermore, a direct interaction between FLPNF and hIAPP was confirmed. FLPNF could also decrease the cytotoxic effect of hIAPP. CONCLUSIONS: The novel pentapeptide inhibitor FLPNF was constructed and inhibited the aggregation through direct binding to hIAPP. It is considered a suitable inhibitor for hIAPP amyloid deposit formation.

Effect of ω-3 polyunsaturated fatty acids on liver function and inflammatory reaction in patients undergoing hepatectomy: a systematic review and meta-analysis of randomized control trials.

INTRODUCTION: Several studies have investigated the relationship between ω-3 polyunsaturated fatty acids (PUFAs) administration and liver function and inflammatory reaction in patients undergoing liver resection, but the results remain conflicting and inconclusive. Areas covered: In this meta-analysis, a relevant database search was performed to retrieve all the randomized controlled trials (RCTs) exploring the effect of ω-3 PUFAs administration in patients undergoing hepatectomy until the end of April 2018. A random effect model was used to conduct this meta-analysis with RevMan 5.3.5 software. The quality of evidence for each postoperative outcome was assessed using the GRADEpro analysis. Expert opinion: 4 RCTs including 553 patients (277 with and 276 without ω-3 PUFAs) were identified. ω-3 PUFAs significantly reduced alanine aminotransferase [Mean difference (MD): -68.82, 95% confidence interval (CI): -108.55 to - 29.08; p = 0.0007]; aspartate aminotransferase (MD: -64.92, 95% CI: -112.87 to -16.98; p = 0.008), white blood cell count (MD: -1.22, 95% CI: -2.15 to -0.29; p = 0.01) and increased the level of pre-albumin on postoperative day 3 (MD: 10.42, 95% CI: 4.84 to 15.99; p = 0.0002). The results indicate that ω-3 PUFAs administration has a positive impact on the liver function and inflammatory reaction in patients undergoing liver resection.

Intraoperative Hepatic Blood Inflow Can Predict Early Acute Kidney Injury following DCD Liver Transplantation: A Retrospective Observational Study.

PURPOSE: Acute kidney injury (AKI) is a major and severe complication following donation-after-circulatory-death (DCD) liver transplantation (LT) and is associated with increased postoperative morbidity and mortality. However, the risk factors and the prognosis factors of AKI still need to be further explored, and the relativity of intraoperative hepatic blood inflow (HBI) and AKI following LT has not been discussed yet. The purpose of this study was to investigate the correlation between HBI and AKI and to construct a prediction model of early acute kidney injury (EAKI) following DCD LT with the combination of HBI and other clinical parameters. METHODS: Clinical data of 132 patients who underwent DCD liver transplantation at the first hospital of China Medical University from April 2005 to March 2017 were analyzed. Data of 105 patients (the first ten years of patients) were used to develop the prediction model. Then we assessed the clinical usefulness of the prediction models in the validation cohort (27 patients). EAKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria based on serum creatinine increase during 7-day of postoperative follow-up. RESULTS: After Least Absolute Shrinkage and Selection Operator (LASSO) regression and simplification, a simplified prediction model consisting of the Child-Turcotte-Pugh (CTP) score (p=0.033), anhepatic phase (p=0.014), packed red blood cell (pRBC) transfusion (p=0.027), and the HBI indexed by height (HBI/h) (p=0.002) was established. The C-indexes of the model in the development and validation cohort were 0.823 [95% CI, 0.738-0.908] and 0.921 [95% CI, 0.816-1.000], respectively. CONCLUSIONS: In this study, we demonstrated the utility of HBI/h as a predictor for EAKI following DCD LT, as well as the clinical usefulness of the prediction model through the combination of the CTP score, anhepatic phase, pRBC transfusion and HBI/h.