Hyperoside Ameliorates Diabetic Retinopathy via Anti-Oxidation, Inhibiting Cell Damage and Apoptosis Induced by High Glucose.

BACKGROUND: Hyperoside (Hyp) is a flavonoid substance extracted from plants, which has the functions of anti-cancer, anti-inflammatory, and anti-oxidation. In the previous study, we found that Hyp reduced the injury of rat retinal vascular endothelial cells (RVECs) induced by H2O2. METHOD: In the present research, we evaluated the protective effect of Hyp on the pathological damage of retina caused by high glucose of diabetes mellitus (DM) in in vitro and in vivo experiments. The effect of Hyp on cell viability, oxidative stress level, and apoptosis of RVECs was assessed. RESULTS: Hyp significantly reduced the of RVECs damage, oxidative stress level, and cell apoptosis induced by high glucose in vitro. In DM model rats, Hyp treatment could significantly reduce blood glucose levels and the pathological damage of retina caused by DM and increase the proliferation of RVECs while exerting the inhibition on apoptotic activity. Furthermore, Hyp treatment decreased the expressions of apoptotic proteins including caspase-3, caspase-9, and Bax in RVECs of DM rats, while increased the expression of anti-apoptotic protein Bcl-2. CONCLUSION: Hyp may have protective effect on diabetes-induced retinopathy by reducing oxidative stress, inhibiting cell damage, and apoptosis induced by high glucose.

Short-term effect and safety of a new generation of monoclonal antibodies targeting interleukin-23p19 for treatment of psoriasis: a systematic review and meta-analysis.

The effect and safety of monoclonal antibodies (mAbs) targeting the interleukin-23 (IL-23) p19 subunit for treatment of psoriasis has not previously been systematically evaluated. To perform a systematic review and meta-analysis of randomized clinical trials (RCTs) (including Phase I-III trials) to evaluate the efficacy and safety of these mAbs for treatment of psoriasis. The databases of PubMed, Baidu Scholar, and Cochrane Library of Clinical Trials were searched from inception of the databases to January 1st, 2018. A systematic review and meta-analysis was conducted using Review Manager Software version 5.3 (RevMan 5.3). Nine RCTs with a total of 2,478 subjects met our inclusion criteria. A significant increase in PASI 75 (RR: 11.65; 95% CI: 9.01-15.06), PASI 90 (RR: 21.74; 95% CI: 14.28-33.10), PASI 100 (RR: 31.56; 95% CI: 14.66-67.96), PGA 0/1 (OR: 23.21; 95% CI: 14.61-36.89), and DLQI 0/1 (RR: 10.29; 95% CI: 7.52-14.09) was identified for anti-IL-23p19 mAb vs. placebo, and PASI 75 (RR: 1.25; 95% CI: 1.18-1.32), PASI 90 (OR: 2.56; 95% CI: 2.13-3.09), PASI 100 (OR: 2.38, 95% CI: 1.89-2.99), and DLQI 0/1 (RR: 1.33; 95% CI: 1.20-1.47) vs. tumour necrosis factor (TNF) antagonists for the treatment of psoriasis. Furthermore, there was no significant difference in adverse events between placebo and TNF antagonists. Anti-IL-23p19 mAbs are effective with acceptable safety as therapy for psoriasis, and may be superior to TNF antagonists. More RCTs with a larger sample size are required to verify the current findings.

Aspirin and heparin for the prevention of pre-eclampsia: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Pre-eclampsia is an important cause of death and complication for pregnant women and perinatal infant. Low-dose aspirin has been most commonly used to prevent pre-eclampsia in high-risk pregnant women. Recently, heparins have also been used alone or in combination with aspirin to prevent pre-eclampsia. However, the optimal doses and combination therapy of aspirin and heparins are not well established. Therefore, we aim to compare aspirin, heparins and their combination to prevent pre-eclampsia in a network meta-analysis. METHODS AND ANALYSIS: We will search the following electronic databases from the date of database establishment to 8 January 2019: PubMed, Embase, Cochrane Library, Web of Science and ProQuest. We will also search additional studies manually. There will be no restriction on the language of publications. Only randomised clinical trials will be eligible in our network meta-analysis. We will include pregnant women who have been recommended for aspirin according to the standard of the American Congress of Obstetricians and Gynecologists, or were designated as high risk in some recent studies. We will include studies comparing the effects of any single or combination of aspirin and heparins with placebo or observation or another intervention in pregnancy. We will include studies that reported one of the following outcomes: pre-eclampsia, severe pre-eclampsia, preterm delivery, perinatal death and full-term pre-eclampsia with delivery at ≥37 weeks. Traditional pairwise meta-analysis will be performed initially, and then network meta-analysis will be performed using frequency analysis method. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. ETHICS AND DISSEMINATION: This network meta-analysis does not require ethical certification. An overview and information on the prevention of pre-eclampsia in high-risk pregnant women will be provided by this network meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42018084248.

A case of Phaeohyphomycosis caused by Corynespora cassiicola infection.

BACKGROUND: Corynespora cassiicola infection is common in plants, but the human Corynespora cassiicola infection in our report is rare according to the literature. CASE PRESENTATION: We report a case of subcutaneous phaeohyphomycosis caused by a plant pathogen in a patient with acute heart failure. The organism was isolated and identified as Corynespora cassiicola according to its morphological characteristics and gene analysis. The patient was treated successfully with systemic voriconazole. CONCLUSIONS: This is the third reported case of subcutaneous infection caused by Corynespora cassiicola and the first reported case with accompanied renal impairment, which was associated with acute heart failure. Our case also suggests the importance of renal function monitoring in patients receiving intravenous voriconazole treatment.

DNA/RNA-based formulations for treatment of breast cancer.

INTRODUCTION: To develop a successful formulation for the gene therapy of breast cancer, an effective therapeutic nucleic acid and a proper delivery system are essential. Increased understanding of breast cancer, and developments in biotechnology, material science and nanotechnology have provided a major impetus in the development of effective formulations for the gene therapy of breast cancer. Areas covered: We discuss DNA/RNA-based formulations that can inhibit the growth of breast cancer cells and control the progress of breast cancer. Targets for the gene therapy of breast cancer, DNA/RNA-based therapeutics and delivery systems are summarized. And examples of successful DNA/RNA-based formulations for breast cancer gene therapy are reviewed. Expert opinion: Several challenges remain in developing effective DNA/RNA-based formulations for treatment of breast cancer. Firstly, most of the currently utilized targets are not effective enough as monotherapy for breast cancer. Secondly, the requirements for co-delivery system make the preparation of formulation more complicated. Thirdly, nanoparticles with the modification of tumor-targeting ligands could be more unstable in circulation and normal tissues. Lastly, immune responses against the viral vectors are unfavorable for the gene therapy of breast cancer because of the damage to the host and the impaired therapeutic ability.

Engineering intravaginal vaccines to overcome mucosal and epithelial barriers.

The mucosal surface of the vagina is a primary human immunodeficiency virus (HIV) entry portal, making it an attractive site for HIV vaccination. However, HIV vaccines based on recombinant adenovirus (rAd) do not efficiently cross the mucus layers or underlying epithelium of the vagina. Here we designed nanocomplexes of rAd particles coated with (1) the polyethylene glycol derivative APS to provide a hydrophilic surface that would prevent entrapment in the hydrophobic mucus, and (2) the cell-penetrating peptide TAT to improve transduction efficiency. The optimized rAd-TAT-APS nanocomplexes could achieve the balance of effective mucus-penetrating and cellular transduction. Intravaginal delivery of rAd-TAT-APS encoding HIVgag p24 into mice strongly enhanced HIVgag-specific systemic and mucosal immune responses. This rAd-TAT-APS system may allow effective vaginal delivery of vaccines against HIV and other infectious agents.

Bradycardia associated with pegylated liposomal doxorubicin administration: a case report.

The cardiotoxicity of doxorubicin is dose dependent and progressive, but its mechanisms remain unclear. Measures to prevent the cardiotoxicity of doxorubicin have had limited success. We report here on a patient who had received intravenous infusion of pegylated liposomal doxorubicin and developed sinus bradycardia despite the prior administration of the iron-chelating agent, dexrazoxane. The adverse effect of pegylated liposomal doxorubicin might be due to the difference in metabolic related genes for anthracyclines. Therefore, monitoring the cardiac condition of patients who receive doxorubicin treatment, even at low doses, is highly recommended.

A Prime-Boost Strategy Combining Intravaginal and Intramuscular Administration of Homologous Adenovirus to Enhance Immune Response Against HIV-1 in Mice.

Immune responses to HIV in the vaginal tract effectively trigger both systemic and mucosal protection, providing a double layer of defense. However, recombinant adenoviral (rAd) vectors delivered intravaginally do not effectively penetrate the mucus layer and vaginal epithelium, and instead are rapidly cleared. To overcome these barriers, we previously synthesized a novel cationic polyethylene glycol derivative that can self-assemble into nanocomplexes with rAd. These nanocomplexes can help rAd bypass the mucus layer and enhance mucosal immune response to the encoded antigen. However, the resulting cellular and humoral responses were still lower than those elicited by single intramuscular injection of rAd. Therefore, in the present study we investigated a new vaccination strategy involving intravaginal priming with our nanocomplexes, followed by an intramuscular boost with rAd-gag. Mice immunized in this way showed more potent humoral and cellular responses, as well as higher IgA levels, than animals primed and boosted intravaginally with nanocomplexes. These results show the promise of a prime-boost strategy for developing vaccine candidates against HIV.

Adenoviral vectors coated with cationic PEG derivatives for intravaginal vaccination against HIV-1.

Mucus layer coating the vaginal epithelium represents a barrier for intravaginally delivered recombined adenoviral (rAd) vectors, but it could be overcome by proper polyethylene glycol (PEG) modification. Here we synthesized two cationic PEG derivatives, amino-(EO)n/(AGE)m-Cyss (APCs). The polymers contained neutral linear PEG (2-5 kDa) to provide a hydrophilic surface and amine pendants to provide positive charge for coating negatively charged rAd by physical adsorption. Given proper molecular composition, the polymer (5k-APC) could coat rAd without causing aggregation, facilitating its mucus penetrating ability and enhancing gene expression both in vitro and in vivo. With HIVgag as the model antigen, the polymer-rAd complexes were administered intravaginally to elicit both systemic and mucosal immune responses. 5k-APC-rAd immunization elicited robust HIVgag-specific cellular responses and also induced higher antigen-specific serum IgG. More importantly, mice immunized with 5k-APC-rAd showed higher level of IgA in vaginal lavage fluid. These findings suggest that 5k-APC-rAd is a promising system for intravaginal immunization against infectious diseases such as HIV within the vaginal tract.

Subchronic toxicity and immunotoxicity of MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer nanoparticles delivered intravenously into rats.

Although monomethoxy(polyethyleneglycol)-poly (D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) nanoparticles have been widely studied as a drug delivery system, little is known about their toxicity in vivo. Here we examined the subchronic toxicity and immunotoxicity of different doses of PELGE nanoparticles with diameters of 50 and 200 nm (PELGE50 and PELGE200) in rats. Neither size of PELGE nanoparticles showed obvious subchronic toxic effects during 28 d of continuous intravenous administration based on clinical observation, body weight, hematology parameters and histopathology analysis. PELGE200 nanoparticles showed no overt signs of immunotoxicity based on organ coefficients, histopathology analysis, immunoglobulin levels, blood lymphocyte subpopulations and splenocyte cytokines. Conversely, PELGE50 nanoparticles were associated with an increased organ coefficient and histopathological changes in the spleen, increased serum IgM and IgG levels, alterations in blood lymphocyte subpopulations and enhanced expression of spleen interferon-γ. Taken together, these results suggest that PELGE nanoparticles show low subchronic toxicity but substantial immunotoxicity, which depends strongly on particle size. These findings will be useful for safe application of PELGE nanoparticles in drug delivery systems.