Mulberry fruit repairs alcoholic liver injury by modulating lipid metabolism and the expression of miR-155 and PPARα in rats.

As alcohol consumption increases, alcoholic liver disease (ALD) has become more popular and is threating our human life. In this study, we found mulberry fruit extract (MFE) repaired alcohol-caused liver diseases by regulating hepatic lipid biosynthesis pathway and oxidative singling in alcoholically liver injured (ALI) rats. MFE administration inhibited hepatic lipid accumulation and improved liver steatosis in ALI rats. MFE also enhanced the antioxidant capacity and alleviated the inflammatory response by increasing the activities of antioxidant enzymes and decreasing the contents of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. Additionally, MFE regulated the expression of miRNA-155 and lipid metabolism-related PPARα protein in rats. Both miR-155 and PPARα play important roles in liver function. The results indicate that MFE has hepatoprotective effects against ALI in rats.

Aflibercept for long-term treatment of diabetic macular edema and proliferative diabetic retinopathy: a meta-analysis.

Purpose: This meta-analysis compared the long-term (12 months or 24 months) efficacy and safety of intravitreal aflibercept injection (IAI) for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Methods: We selected 16 randomized controlled trials (RCTs) performed after 2015 that had a minimum of 12 months and up to 24 months of treatment and conducted a meta-analysis with Review Manager version 5.3. Visual acuity (VA), central subfield thickness (CST) and adverse events were the outcomes selected for evaluation from the eligible studies. Results: Based on 16 RCTs, we evaluated a total of 7125 patients. For PDR and severe DME with poor baseline vision, after a minimum of 12 months and up to 24 months of treatment, the aflibercept treatment group obtained better VA improvement than the focal/grid laser photocoagulation treatment group (MD=13.30; 95%CI: 13.01~13.58; P<0.001) or other treatments (ranibizumab, focal/grid laser photocoagulation, PRP, et al.) group (MD=1.10; 95%CI: 1.05~1.16; P<0.001). In addition, the aflibercept treatment group got higher CST reduction than the focal/grid laser photocoagulation treatment (MD=-33.76; 95%CI: -45.53 ~ -21.99; P<0.001) or other treatments (ranibizumab, focal/grid laser photocoagulation, et al.) group (MD=-33.76; 95%CI: -45.53 ~ -21.99; P<0.001). There was no significant difference in the overall incidence of ocular and non-ocular adverse events in each treatment group. Conclusions: This meta-analysis showed that the advantages of IAI are obvious in the management of DME and PDR with poor baseline vision for long-term observation (a minimum of 12 months and up to 24 months) with both VA improvement and CST reduction. Applied IAI separately trended to be more effective than panretinal photocoagulation separately in VA improvement for PDR. More parameters should be required to assess functional and anatomic outcomes.

Pan-cancer analysis of the oncogenic effects of G-protein-coupled receptor kinase-interacting protein-1 and validation on liver hepatocellular carcinoma.

BACKGROUND: Despite G-protein-coupled receptor kinase-interacting protein-1 (GIT1) being recognized as a new promoter gene in some types of cancer, its effect on human pan-cancers and liver hepatocellular carcinoma (LIHC) remains unclear. OBJECTIVES: To elucidate the molecular mechanisms of GIT1 in pan-cancer and LIHC. MATERIAL AND METHODS: Various bioinformatics approaches were utilized to elucidate the oncogenic effects of GIT1 on human pan-cancers. RESULTS: The GIT1 was aberrantly expressed in pan-cancers and associated with the clinical stage. Moreover, the upregulation of GIT1 expression was indicative of poor overall survival (OS) in patients with LIHC, skin cutaneous melanoma (SKCM) and uterine corpus endometrial carcinoma (UCEC), as well as of poor disease-free survival (DFS) in patients with LIHC and UCEC. Furthermore, GIT1 levels were correlated with cancer-associated fibroblasts (CAFs) in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma (CESC) and LIHC. The analysis of single-cell sequencing data revealed an association of GIT1 levels with apoptosis, cell cycle and DNA damage. In addition, multivariate Cox analysis indicated that high GIT1 levels were an independent risk factor for shorter OS in patients with LIHC. Finally, the gene set enrichment analysis revealed INFLAMMATORY_RESPONSE pathway and IL2_STAT5_SIGNALING to be the most enriched in LIHC. CONCLUSIONS: Our data demonstrate the oncogenic effects of GIT1 on various cancers. We believe that GIT1 can serve as a biomarker for LIHC.

A mitochondria-targeted nano-platform for pancreatic cancer therapy.

Liposome is a conventional drug delivery system which has been widely used in the pharmacy field. However, its applications are greatly restricted in clinical practice by the disadvantages of cholesterol and nonselective distribution. Herein, a novel platform for anti-tumor drug delivery was developed by incorporating an amphiphilic stachydrine-octadecane conjugate (SS) as the mitochondria-targeting molecule onto the triptolide-liposome surfaces (SS-TP LPs). The polyethylene glycol (PEG) and the suitable particle size (about 133 nm) of liposomes facilitated their stabilities, the long half-life in blood and the escape from the rapid elimination. The SS-TP LPs were internalized and accumulated into the mitochondria of cancer cells in a time-dependent manner, followed by triggering permeabilization of the mitochondrial outer membrane by inhibiting Bcl-2, and then further caused greater cancer cell death via releasing cytochrome C and initiating a cascade of caspase 3 reactions. In the Pan02 tumor-bearing mice, the SS-TP LPs showed significant efficacy in inhibiting tumor growth and reducing tumor size but synchronously exhibited specific mitochondria-targeting and much lower subacute toxicity compared with the free TP and TP LPs. Our study suggests that SS-TP LPs can be a promising anticancer drug delivery system for mitochondria-targeted therapy in pancreatic cancer.

Analysis of the aqueous humor lipid profile in patients with polypoidal choroidal vasculopathy.

This study aimed to investigate the lipid profiles of aqueous humor from polypoidal choroidal vasculopathy (PCV) patients and identify potential biomarkers to increase the understanding of PCV pathomechanism. An ultra-high performance liquid chromatography-tandem mass spectrometry based untargeted lipidomic analysis was performed to acquire lipid profiles of aqueous humor of PCV patients and control subjects. Differentially expressed lipids were identified by univariate and multivariate analyses. A receiver operator characteristic curve (ROC) analysis was conducted to confirm the potential of identified lipids as biomarkers. Sixteen PCV patients and twenty-eight control subjects were enrolled in this study. In total, we identified 33 lipid classes and 639 lipid species in aqueous humor using the LipidSearch software. Of them, 50 differential lipids were obtained by combining univariate and multivariate statistical analyses (VIP>1 and P < 0.05), and 19 potential lipid biomarkers were identified by ROC analysis. In addition, significant alterations were found in several metabolic pathways, including glycerophospholipid, glycerolipid, and glycosylphosphatidylinositol-anchor biosynthesis. This study is the first to systematically characterize the alterations in lipid profiles in aqueous humor of PCV patients and screen for the potential lipid biomarkers for PCV diagnosis and treatment intervention. The results of this study are likely to broaden our understanding of the pathogenesis of PCV and contribute to improvements in the diagnosis and treatment of the disease.

Incidence and risk factors of perioperative venous thromboembolism in patients with cervical cancer.

The aim of this retrospective study was to identify the perioperative incidence and risk factors of venous thromboembolism (VTE) in patients undergoing surgery for cervical cancer. The retrospective medical records of consecutive patients with cervical cancer were collected at the Qianfoshan Hospital affiliated with Shandong University from July 2014 to July 2017. Basic information regarding the patients, as well as tumor and surgery-related factors were compared between the cervical cancer patients with and without VTE. In the present study, a total of 338 patients undergoing surgery for cervical cancer were included. Ten (3.0%) patients were diagnosed with preoperative VTE and 18 (5.5%) with postoperative VTE. Multivariate analyses found that high levels of D-dimer and a larger size of the cervical tumor were independent risk factors for preoperative VTE, whereas the length of surgery and use of chemotherapy were independently associated with VTE development within 30 days after surgery. In conclusion, the major findings of the present study was a significant incidence of VTE in patients with cervical cancer. We also identified the clinical characteristics which can cause cervical cancer patients to have an increased risk for VTE.

Anti-Tumor and Anti-Metastasis Effects of Berbamine-Loaded Lipid Nanoparticles on Pancreatic Cancer.

OBJECTIVE: The aim of the study was to investigate the therapeutic potential of Berbamine-loaded lipid nanoparticles (BBM-NPs) in pancreatic cancer. METHODS: Dopamine polymerization-polylactide-TPGS nanoparticles were synthesized to prepare BBM-NPs, and the change in particle size of BBM-NPs was measured. Cell Counting Kit-8 (CCK8) assay, plate cloning experiment, and apoptosis analysis were performed to evaluate the cytotoxicity of BBM-NPs against the pancreatic cancer cells (PANC-1 and AsPC-1). Migration and invasion abilities of the tumor cells were determined by Transwell and wound healing assays. The intracellular level of ROS and expression of tumor progression-related proteins were measured using ROS-kit and western blot assay. Besides, an in vivo study was performed in the Balb/c nude mice to analyze the function of BBM-NPs in tumor growth. RESULTS: The in vitro studies showed that BBM-NPs with stable particle size and sustained drug release effectively inhibited the viability, proliferation, migration, and invasion of pancreatic cancer cells, while promoting cell apoptosis. Moreover, the in vivo experiments revealed that compared to Free BBM, BBM-NPs exhibited a stronger inhibitory effect on the growth of xenograft tumors derived from PANC-1 cells in mice. In addition, increased expressions of ROS, Bax, Cleaved Caspase-3, and γ-H2AX, as well as decreased expressions of MMP2, MMP9 and Bcl-2 were identified in both Free BBM and BBM-NPs groups, while BBM-NPs exhibited a stronger effect on protein expression than Free BBM. CONCLUSION: In summary, BBM-loaded lipid nanoparticles enhanced the therapeutic effects of BBM on pancreatic cancer, providing a promising strategy for targeted cancer therapy.

Dextran-polylactide micelles loaded with doxorubicin and DiR for image-guided chemo-photothermal tumor therapy.

Image-guided chemo-photothermal therapy based on near-infrared (NIR) theranostic agents has found promising applications in treating tumors. In this multimodal treatment, it is of critical importance to image real-time distribution of photothermal agents in vivo and to monitor therapeutic outcomes for implementing personalized treatment. In this study, an optimally synthesized dextran-polylactide (DEX-PLA) copolymer was assembled with doxorubicin (DOX) and DiR, a kind of NIR dye, to construct desirable micelles ((DiR + DOX)/DEX-PLA) for performing image-guided chemo-photothermal therapy. These (DiR + DOX)/DEX-PLA micelles had good physical and photothermal stability in aqueous media and showed high photothermal efficiency in vivo. Based on the H22-tumor-bearing mouse model, (DiR + DOX)/DEX-PLA micelles were found to accumulate inside tumors sustainably and to emit strong fluorescence signals for more than three days. The (DiR + DOX)@DEX-PLA micelles together with NIR laser irradiation were able to highly inhibit tumor growth or even eradicate tumors with one injection and two dose-designated 5-minute laser irradiations at the tumor site during 14 days of treatment. Furthermore, they showed almost no impairment to the body of the treated mice. These (DiR + DOX)@DEX-PLA micelles have confirmative translational potential in clinical tumor therapy on account of their persistent image-guided capacity, high antitumor efficacy and good in vivo safety.

Unveiling the Activity Origin of Iron Nitride as Catalytic Material for Efficient Hydrogenation of CO2 to C2+ Hydrocarbons.

Developing efficient catalytic materials and unveiling the active species are significant for selective hydrogenation of CO2 to C2+ hydrocarbons. Fe2 N@C nanoparticles were reported to exhibit outstanding performance toward selective CO2 hydrogenation to C2+ hydrocarbons (C2+ selectivity: 53.96 %; C2 -C4 = selectivity, 31.03 %), outperforming corresponding Fe@C. In situ X-ray diffraction, ex situ Mössbauer and X-ray photoelectron spectra revealed that iron nitrides were in situ converted to highly active iron carbides, which acted as the real active species. Moreover, the combined results of in situ diffuse reflectance infrared Fourier transform spectroscopy and control experiments suggested an in situ formed carbonyl iron-mediated conversion mechanism from iron nitrides to iron carbides.

Quality assessment of the guidelines for the management of malignant pleural effusions and ascites.

OBJECTIVES: To fully assess the quality of the guidelines for the management of malignant pleural effusions (MPE) and ascites and reveal the heterogeneity of recommendations and possible reasons among guidelines. METHODS: A systematic search was performed in the database to obtain guidelines for the management of MPE and ascites. The AGREE IIGtool was used to assess the quality of these guidelines. The Measurement Scale of Rate of Agreement (MSRA) was introduced to assess the scientific agreement of formulated recommendations for the management of MPE and ascites among guidelines, and evidence supporting these recommendations was extracted and analyzed. RESULTS: Nine guidelines were identified. Only 4 guidelines scored more than 60% and are worth recommending. Recommendations were also heterogeneous among guidelines for the management of MPE, and the main reasons were the different emphases of the recommendations for the treatment of MPE, the contradictions in recommendations, and the unreasonably cited evidence for MPE. CONCLUSIONS: The quality of the management guidelines for patients with MPE and malignant ascites was highly variable. Specific improvement of the factors leading to the heterogeneity of recommendations will be a reasonable and effective way for developers to upgrade the recommendations in the guidelines for MPE.

Augmented Graphene Quantum Dot-Light Irradiation Therapy for Bacteria-Infected Wounds.

This paper proposes a highly efficient antibacterial system based on a synergistic combination of photodynamic therapy, photothermal therapy, and chemotherapy. Chitosan oligosaccharide functionalized graphene quantum dots (GQDs-COS) with short-term exposure to 450 nm visible light are used to promote rapid healing in bacteria-infected wounds. The GQDs undergo strong photochemical transformation to rapidly produce radical oxygen species and heat under light illumination, while the COS has an innate antimicrobial ability. Moreover, the positively charged GQDs-COS can easily capture bacteria via electrostatic interactions and kill Gram-positive and Gram-negative bacteria by multivalent interactions and synergistic effects. The antibacterial action of this nanocomposite causes irreversible damage to outer and inner bacterial membranes, resulting in cytoplasm leakage and death. The system has good hemocompatibility and low cytotoxicity and can improve the healing of infected wounds, as demonstrated by the examination of pathological tissue sections and inflammatory markers. These results suggest that GQDs anchored with bioactive molecules are a potential photo-activated antimicrobial strategy for anti-infective therapy.

Efficacy of neoadjuvant chemotherapy combined with intraperitoneal hyperthermic chemotherapy in advanced ovarian cancer.

PURPOSE: To explore the efficacy and safety of neoadjuvant chemotherapy (NAC) combined with cytoreductive surgery (CRS) and postoperative intraperitoneal hyperthermic chemotherapy (IPHC) in the treatment of advanced ovarian cancer. METHODS: 132 patients with advanced ovarian cancer admitted to our hospital from May 2013 to May 2016 were enrolled and randomly divided into control group (n=44), IPHC group (n=44) and NAC+IPHC group (n=44). The patients in the control group underwent CRS and postoperative TP chemotherapy (iv. drip of paclitaxel + peritoneal perfusion of cisplatin), those in IPHC group underwent the CRS and postoperative IPHC+TP chemotherapy, and those in the NAC+IPHC group received two cycles of preoperative NAC and postoperative IPHC+TP chemotherapy. The surgery indexes (operation time, amount of intraoperative bleeding, diameter of tumor and number of metastatic foci) were recorded. The clinical effective rate, changes in levels of serum tumor markers and adverse reactions were evaluated. Moreover, the tumor recurrence and survival of patients after treatment were recorded. RESULTS: In NAC + IPHC group, the operation time, amount of intraoperative bleeding and of ascites, diameter of tumor and number of metastatic foci were all significantly reduced, and the optimal cytoreduction rate was increased compared with IPHC group and control group. The clinical effective rate was 43.2% (19/44), 61.4% (27/44) and 72.7% (32/44), respectively, in the three groups, with significant differences, and the clinical effective rate was obviously higher in NAC+IPHC group than in control group, while it had no significant difference in IPHC group compared with NAC+IPHC group or control group. After treatment, the levels of serum human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) were evidently higher in NAC + IPHC group than in IPHC group, while they were also evidently higher in IPHC group than in control group. According to the follow-up results, the 1-year recurrence rate in NAC+IPHC group was remarkably lower than in control group, and the median progression-free survival in NAC+IPHC group and IPHC group was remarkably longer than in control group, while it had no significant difference between NAC+IPHC group and IPHC group. The median overall survival had no statistically significant differences among the three groups. CONCLUSIONS: NAC combined with IPHC can significantly reduce the perioperative risk, increase the optimal cytoreduction rate and raise the clinical effective rate of CRS in the treatment of advanced ovarian cancer. Moreover, patients have good tolerance, and both tumor progression and survival of patients are significantly improved.

Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity.

Background: Photothermal therapy (PTT) has been demonstrated to be a promising cancer treatment approach because it can be modulated to induce apoptosis instead of necrosis via adjusting irradiation conditions. Recently, an abscopal anti-tumor immunity has been highlighted, in which PTT on the primary tumor also induced repression of distant tumors. In PTT cancer treatments, the mechanism and the role of immune checkpoints to enhance anti-tumor immunity needs to be investigated. Methods: We prepared a multi-functional gold nanorod reagent, GMPF-siIDO, that is composed of gold nanorods (GNRs) that act as the nano-platform and photothermal sensitizer; folic acid (FA) as the tumor-targeting moiety; and IDO-specific RNA (siIDO) as an immune-stimulator functionality for inducing anti-tumor immunity. For this study, we adjusted the irradiation condition of PTT to induce apoptosis and to silence the immune checkpoint indoleamine 2,3 dioxygeonase (IDO), simultaneously. Results: Our studies provide evidence that photothermal effects kill tumor cells mainly via inducing apoptosis, which can significantly improve antitumor immunity when IDO was down-regulated in TME through significant increases of localized CD8+ and CD4+ lymphocytes in tumor tissue, the downregulation of CD8+ and CD4+ lymphocyte apoptosis, and the upregulation of antitumor cytokines, TNF-α and IFN-γ. Conclusion: In this study, we, for the first time, validated the role of IDO as a negative regulator for both PTT-induced tumor cell apoptosis and anti-tumor immunity; IDO is a critical immune checkpoint that impedes PTT while combination of gene knockdown of IDO in TME enhances anti-tumor efficacy of PTT.

miRNA-5119 regulates immune checkpoints in dendritic cells to enhance breast cancer immunotherapy.

Dendritic cell (DC) based immunotherapy is a promising approach to clinical cancer treatment. miRNAs are a class of small non-coding RNA molecules that bind to RNAs to mediate multiple events which are important in diverse biological processes. miRNA mimics and antagomirs may be potent agents to enhance DC-based immunotherapy against cancers. miRNA array analysis was used to identify a representative miR-5119 potentially regulating PD-L1 in DCs. We evaluated levels of ligands of immune cell inhibitory receptors (IRs) and miR-5119 in DCs from immunocompetent mouse breast tumor-bearing mice, and examined the molecular targets of miR-5119. We report that miRNA-5119 was downregulated in spleen DCs from mouse breast cancer-bearing mice. In silico analysis and qPCR data showed that miRNA-5119 targeted mRNAs encoding multiple negative immune regulatory molecules, including ligands of IRs such as PD-L1 and IDO2. DCs engineered to express a miR-5119 mimic downregulated PD-L1 and prevented T cell exhaustion in mice with breast cancer homografts. Moreover, miR-5119 mimic-engineered DCs effectively restored function to exhausted CD8+ T cells in vitro and in vivo, resulting in robust anti-tumor cell immune response, upregulated cytokine production, reduced T cell apoptosis, and exhaustion. Treatment of 4T1 breast tumor-bearing mice with miR-5119 mimic-engineered DC vaccine reduced T cell exhaustion and suppressed mouse breast tumor homograft growth. This study provides evidence supporting a novel therapeutic approach using miRNA-5119 mimic-engineered DC vaccines to regulate inhibitory receptors and enhance anti-tumor immune response in a mouse model of breast cancer. miRNA/DC-based immunotherapy has potential for advancement to the clinic as a new strategy for DC-based anti-breast cancer immunotherapy.

Ag-Conjugated graphene quantum dots with blue light-enhanced singlet oxygen generation for ternary-mode highly-efficient antimicrobial therapy.

The increasing prevalence of antibiotic resistance highlights the need for new antibacterial drugs and, in particular, the development of alternative approaches such as photodynamic therapy (PDT) and photothermal therapy (PTT) to manage this growing issue. In the present study, a broad-spectrum antibacterial system was produced in which Ag nanoparticle-conjugated graphene quantum dots (GQD-AgNP) were utilised as a blue light-enhanced nanotherapeutic for efficient ternary-mode antimicrobial therapy. The successful conjugation of AgNPs onto the surface of GQDs can significantly improve the production of reactive oxygen species in light-activatable GQDs and the transformation of light energy to hyperthermia with high efficiency. There was a remarkable increase in the sample temperature of nearly 40 °C via photoexcitation after only 10 min of 450 nm laser exposure (14.2 mW cm-2). The hybrids exhibited much more efficient bactericidal capability against both Gram-negative and Gram-positive bacteria compared with GQDs alone, using 450 nm light irradiation. This is likely a consequence of their enhanced PDT, concomitant PTT, and the synergistic function of AgNPs. The antibacterial mechanism of the new-style nanocomposites was found to irreversibly destroy the bacterial membrane structure, leading to the leaking out of the cytoplasmic contents and the death of the bacteria. At low doses, the biocompatible GQD-AgNP hybrids promoted healing in bacteria-infected rat wounds, with negligible adverse impact to the normal tissue, indicating a promising future for combined photodynamic and photothermal antibacterial applications in clinical medicine.

Long noncoding RNA CHL1-AS1 promotes cell proliferation and migration by sponging miR-6076 to regulate CHL1 expression in endometrial cancer.

Endometrial cancer (EC) is deemed to be the most typical gynecologic malignant tumor. Despite the incidence of EC being lower in Asia than that in western countries, substantial increased incidence has been observed in the past few decades in Asia. Although various molecular testing methods and genomic science have developed, the overall prognosis is still disappointing. LncRNAs have been found to influence the progression of various cancers. CHL1-AS1 has been found to be upregulated in ovarian endometriosis, nevertheless, the molecular mechanism and biological function of CHL1-AS1 in EC have not been explored. In our exploration, both CHL1-AS1 and CHL1 were upregulated in EC cells. Knockdown of CHL1-AS1 or CHL1 inhibited cell proliferation and migration in EC. Furthermore, microRNA-6076 (miR-6076) could bind with CHL1-AS1 or CHL1, and regulate the expression of CHL1. Finally, absence of miR-6076 or overexpression of CHL1 can partially rescue the effect of CHL1-AS1 knockdown or miR-6076 upregulation on cell proliferation and migration, respectively. All in all, our research was the first endeavor to study the underlying mechanism of CHL1-AS1 in EC and confirmed that CHL1-AS1 regulated EC progression via targeting the miR-6076/CHL1 axis, offering new insight into treating EC.

miR-149-3p reverses CD8+ T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells.

Blockade of inhibitory receptors (IRs) is one of the most effective immunotherapeutic approaches to treat cancer. Dysfunction of miRNAs is a major cause of aberrant expression of IRs and contributes to the immune escape of cancer cells. How miRNAs regulate immune checkpoint proteins in breast cancer remains largely unknown. In this study, downregulation of miRNAs was observed in PD-1-overexpressing CD8+ T cells using miRNA array analysis of mouse breast cancer homografts. The data reveal that miR-149-3p was predicted to bind the 3'UTRs of mRNAs encoding T-cell inhibitor receptors PD-1, TIM-3, BTLA and Foxp1. Treatment of CD8+ T cells with an miR-149-3p mimic reduced apoptosis, attenuated changes in mRNA markers of T-cell exhaustion and downregulated mRNAs encoding PD-1, TIM-3, BTLA and Foxp1. On the other hand, T-cell proliferation and secretion of effector cytokines indicative of increased T-cell activation (IL-2, TNF-α, IFN-γ) were upregulated after miR-149-3p mimic treatment. Moreover, the treatment with a miR-149-3p mimic promoted the capacity of CD8+ T cells to kill targeted 4T1 mouse breast tumour cells. Collectively, these data show that miR-149-3p can reverse CD8+ T-cell exhaustion and reveal it to be a potential antitumour immunotherapeutic agent in breast cancer.

In Situ Electrochemical Conversion of an Ultrathin Tannin Nickel Iron Complex Film as an Efficient Oxygen Evolution Reaction Electrocatalyst.

The oxygen evolution reaction (OER) is an important half reaction in many energy conversion and storage techniques. However, the development of a low-cost easy-prepared OER electrocatalyst with high mass activity and rapid kinetics is still challenging. Herein, we report the facile deposition of tannin-NiFe (TANF) complex film on carbon fiber paper (CP) as a highly efficient OER electrocatalyst. TANF gives rapid OER reaction kinetics with a very small Tafel slope of 28 mV dec-1 . The mass activity of TANF reaches 9.17×103  Ag-1 at an overpotential of 300 mV, which is nearly 200-times larger than that of NiFe double layered hydroxide. Furthermore, tannic acid in TANF can be electrochemically extracted under anodic potential, leaving the inorganic composite Nix Fe1-x Oy Hz as the OER-active species. This work may provide a guide to probing the electrochemical transformation and investigating the reactive species of other metal-organic complexes as heterogeneous electrocatalysts.

A meta-analysis of adoptive immunotherapy in postoperative hepatocellular carcinoma.

BACKGROUND: Adoptive immunotherapy (AIT) has been adopted as an adjuvant treatment for hepatocellular carcinoma (HCC) patients after curative therapy. However, the outcomes of AIT remain controversial. PURPOSE: The purpose of this study is to analyze the safety and efficacy of AIT with the recurrence rate and mortality. MATERIALS AND METHODS: We identified eight randomized controlled trials (RCTs) that adopted AIT to HCC after curative treatments. A meta-analysis was carried out to assess the recurrence rate and mortality. RESULTS: Eight RCTs with 964 patients were included in the study. The overall analysis showed that AIT treatment can not only decrease the 1-year (risk ratio [RR] =0.59, 95% confidence interval [95% CI] = 0.48-0.72, P < 0.00001), 2-year (RR = 0.69, 95% CI = 0.60-0.79, P < 0.00001), and 3-year (RR = 0.82, 95% CI = 0.74-091, P = 0.0001) recurrence, but also decrease the 1-year (RR = 0.43, 95% CI = 0.30-0.62, P = 0.00001), 2-year (RR = 0.56, 95% CI = 0.46-0.74, P < 0.00001), and 3-year (RR = 0.85, 95% CI = 0.73-0.99, P = 0.03) mortality. The results also indicate that the group of lymphokine-activated killer (LAK) cells showed lower pooled RR values compared to the group of cytokine-induced killer cells among every subgroups. However, the AIT treatment failed to affect the 5-year recurrence rate and mortality (P > 0.05). CONCLUSIONS: This review provides available evidences that AIT, especially the treatment of LAK, can be used to decrease the early recurrence and mortality of postoperative HCC but may not the long term.

A new cancer immunotherapy via simultaneous DC-mobilization and DC-targeted IDO gene silencing using an immune-stimulatory nanosystem.

The activity of negative immune regulatory molecules, such as indoleamine 2,3-oxygenase (IDO), significantly attenuates DC (Dendritic cells)-mediated immunotherapy. We have previously reported that knockdown of IDO using siRNA can reinstall anti-tumor immunity. However, a DC-targeted siRNA delivery system for in vivo mobilized DCs remains to be developed, while gene silencing in mobilized DCs for cancer immunotherapy has never been explored. In our study, we developed a novel DC-targeted siRNA delivery system, man-GNR-siIDO, using as a nanocarrier of siRNA specific for IDO (siIDO) and mannose (man) as a guide molecule for targeting DCs. We explored the immunostimulatory man-GNR-siIDO nano-construct in DCs mobilized by Flt3-L, a receptor-type tyrosine kinase ligand, for lung cancer immunotherapy. In vivo DC-targeted gene silencing of IDO resulted in robust anti-tumor immunity as evidenced by promoting DC maturation, up-regulating tumor antigen-specific T-cell proliferation and enhancing tumor-specific cytotoxicity. A combinatorial treatment for Lewis Lung Carcinoma (LLC)-bearing mice, with man-GNR-siIDO and Flt3-L, significantly attenuated tumor growth and delayed tumor formation, suggesting the treatment feasibility of the man-GNR-siIDO system in Flt3-L mobilized DCs in the immunotherapy of lung cancer. Therefore, our study highlights a clinical potential for a first-in-class anti-cancer immunotherapy through simultaneous DC-mobilization and DC-targeted gene silencing of IDO with man-GNR-siIDO and Flt3-L treatments.