Efficacy and safety of intravitreal injections of conbercept for the treatment of idiopathic choroidal neovascularization.

BACKGROUND: To determine the efficacy and safety of intravitreally injected conbercept, a vascular endothelial growth factor receptor fusion protein, for the treatment of idiopathic choroidal neovascularization (ICNV). METHODS: This retrospective study analyzed outcomes in 40 patients (40 eyes) with ICNV who received intravitreal injections of conbercept 0.5 mg (0.05 ml) and were followed up for at least 12 months. All patients underwent full ophthalmic examinations, including best-corrected vision acuity (BCVA), intraocular pressure (IOP), slit-lamp examination, color fundus photography, optical coherence tomography angiography, multifocal electroretinogram, and fundus fluorescence angiography, if necessary, at baseline and after 1, 3, 6, and 12 months. BCVA, macular central retinal thickness (CRT), IOP, CNV blood flow area, thickness of the CNV-pigment epithelial detachment complex, thickness of the retinal nerve fiber layer (RNFL), and the first positive peak (P1) amplitude density in ring 1 before and after treatment were compared. RESULTS: Mean baseline BCVA (logMAR), CRT, CNV blood flow area, and CNV-pigment epithelial detachment complex thickness were significantly lower 1, 3, 6, and 12 months after than before conbercept treatment (P < 0.05 each). IOP and baseline RNFL thickness were unaffected by conbercept treatment. P1 amplitude density was significantly higher 1, 3, 6, and 12 months after than before conbercept treatment (P < 0.05 each). None of the 40 eyes showed obvious ocular adverse reactions, such as endophthalmitis, glaucoma, cataract progression, and retinal detachment, and none of the patients experienced systemic adverse events, such as cardiovascular and cerebrovascular accidents. CONCLUSIONS: Intravitreal injection of conbercept is beneficial to eyes with ICNV, inducing the recovery of macular structure and function and improving BCVA, while not damaging the neuroretina. Intravitreal conbercept is safe and effective for the treatment of ICNV.

Long Non-Coding RNA Dancr Affects Myocardial Fibrosis in Atrial Fibrillation Mice via the MicroRNA-146b-5p/Smad5 Axis.

Objectives: Atrial fibrillation (AF) is the most frequent arrhythmia, and myocardial fibrosis (MF) has a close association with atrial remodeling and leads to AF. This study aimed to explore the function of the long non-coding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (Dancr)/microRNA (miR)-146b-5p/Smad5 axis on MF in AF mice. Methods: AF mouse models were established. Overexpression Dancr lentivirus was injected into AF mice to increase Dancr expression in myocardial tissues. LncRNA Dancr, miR-146b-5p, and Smad5 expression levels and inflammatory factors (IL-18 and TNF-α) in the myocardial tissues were measured. MF was measured and the expression levels of MF-related genes (COL1A1, α-SMA, and FN1) were detected. In addition, in vitro HL-1 cell rapid pacing models were constructed, and after lncRNA Dancr and miR-146b-5p-related construct transfection, cell viability and cell apoptosis were determined. Results: LncRNA Dancr up-regulation ameliorated MF in the AF mice, reduced IL-18 and TNF-α expression levels in myocardial tissues, and decreased COL1A1, α-SMA, and FN1 expression levels. The in vitro HL-1 cell rapid pacing models suggested that miR-146b-5p overexpression reversed the inhibitory effects of lncRNA Dancr overexpression on MF in HL-1 cells, and Smad5 interference reversed the ameliorative effects of miR-146b-5p interference on MF in HL-1 cells. Conclusions: LncRNA Dancr can sponge miR-146b-5p to promote Smad5 expression, thereby delaying MF in AF mice.

Chiral polypeptide nanoparticles as nanoadjuvants of nanovaccines for efficient cancer prevention and therapy.

The chirality of bioactive molecules is closely related to their functions. D-amino acids commonly distributed in the bacterial cell walls trigger a robust anti-infective immune response. Inspired by that, two kinds of chiral polypeptides, poly(L-phenylalanine)-block-poly(L-lysine) (PL-K) and poly(L-phenylalanine)-block-poly(D-lysine) (PD-K), were synthesized and used as nanoadjuvants of nanovaccines for cancer prevention and therapy. The amphiphilic polypeptides self-assembled into nanoparticles with a diameter of about 30 nm during ultrasonic-assisted dissolution in phosphate-buffered saline. The nanovaccines PL-K-OVA and PD-K-OVA were easily prepared by mixing solutions of PL-K or PD-K and the model antigen chicken ovalbumin (OVA), respectively, with loading efficiencies of almost 100%. Compared to PL-K-OVA, PD-K-OVA more robustly induced dendritic cell maturation, antigen cross-presentation, and adaptive immune response. More importantly, it effectively prevented and treated the OVA-expressed B16-OVA melanoma model. PD-K-OVA achieved a tumor inhibition rate of 94.9% and even 97.0% by combining with anti-PD-1 antibody. Therefore, the chiral polypeptide nanoparticles represent simple, efficient, and extensively applicable nanoadjuvants for various nanovaccines.

Drug-Coated Balloons for De Novo Coronary Artery Lesions: A Meta-Analysis of Randomized Clinical Trials.

PURPOSE: Through meta-analysis, we aimed to assess the efficacy and safety of drug-coated balloons (DCB), compared with drug-eluting stents (DES) or uncoated devices, in the treatment of de novo coronary lesions. MATERIALS AND METHODS: Only randomized controlled trials were included. The primary outcomes were late lumen loss (LLL), target lesion revascularization (TLR), and major adverse cardiac events (MACEs). Subgroup analyses were conducted based on clinical indications, whether DCBs were used with a systematic or bailout stent, and types of DESs. RESULTS: The present meta-analysis demonstrated that DCBs elicit significantly lower incidences of TLR, MACE, and LLL, compared with uncoated devices, and similar incidences, compared with DESs, in the treatment of de novo coronary lesions. Subgroup analysis indicated that DCBs used with a bailout stent achieved lower incidences of binary restenosis and myocardial infarction, compared with uncoated devices, and provided less LLL than DESs. DCBs showed similar rates of TLR and MACE, with significantly less LLL, than DESs in treating de novo small-vessel diseases. The clinical efficacy of DCBs was similar to that of second-generation DES. CONCLUSION: Overall, DCB is favored over bare metal stent alone in treating de novo coronary lesions. DCBs appear to be a promising alternative to DESs in the treatment of de novo coronary lesions.

Acidity-Triggered Transformable Polypeptide Self-Assembly to Initiate Tumor-Specific Biomineralization.

Biomineralization is a normal physiological process that includes nucleation, crystal growth, phase transformation, and orientation evolution. Notably, artificially induced biomineralization in the tumor tissue has emerged as an unconventional yet promising modality for malignancy therapy. However, the modest ion-chelating capabilities of carboxyl-containing biomineralization initiators lead to a deficient blockade, thus compromising antitumor efficacy. Herein, a biomineralization-inducing nanoparticle (BINP) is developed for blockade therapy of osteosarcoma. BINP is composed of dodecylamine-poly((γ-dodecyl-l-glutamate)-co-(l-histidine))-block-poly(l-glutamate-graft-alendronate) and combines a cytomembrane-insertion moiety, a tumor-microenvironment (TME)-responsive component, and an ion-chelating motif. After intravenous injection into osteosarcoma-bearing mice, BINP responds to the acidic TME to expose the dodecyl group on the surface of the expanded nanoparticles, facilitating their cytomembrane insertion. Subsequently, the protruding bisphosphonic acid group triggers continuous ion deposition to construct a mineralized barrier around the tumor, which blocks substance exchange between the tumor and surrounding normal tissues. The BINP-mediated blockade therapy displays tumor inhibition rates of 59.3% and 52.1% for subcutaneous and orthotopic osteosarcomas, respectively, compared with the Control group. In addition, the suppression of osteoclasts by the alendronate moiety alleviates bone dissolution and further inhibits pulmonary metastases. Hence, the BINP-initiated selective biomineralization provides a promising alternative for clinical osteosarcoma therapy.

Development of stimuli responsive polymeric nanomedicines modulating tumor microenvironment for improved cancer therapy.

The complexity of the tumor microenvironment (TME) severely hinders the therapeutic effects of various cancer treatment modalities. The TME differs from normal tissues owing to the presence of hypoxia, low pH, and immune-suppressive characteristics. Modulation of the TME to reverse tumor growth equilibrium is considered an effective way to treat tumors. Recently, polymeric nanomedicines have been widely used in cancer therapy, because their synthesis can be controlled and they are highly modifiable, and have demonstrated great potential to remodel the TME. In this review, we outline the application of various stimuli responsive polymeric nanomedicines to modulate the TME, aiming to provide insights for the design of the next generation of polymeric nanomedicines and promote the development of polymeric nanomedicines for cancer therapy.

Aptamer Nanomaterials for Ovarian Cancer Target Theranostics.

Ovarian cancer is among the leading causes of gynecological cancer-related mortality worldwide. Early and accurate diagnosis and an effective treatment strategy are the two primary means of improving the prognosis of patients with ovarian cancer. The development of targeted nanomaterials provides a potentially efficient strategy for ovarian cancer theranostics. Aptamer nanomaterials have emerged as promising nanoplatforms for accurate ovarian cancer diagnosis by recognizing relevant biomarkers in the serum and/or on the surface of tumor cells, as well as for effective ovarian cancer inhibition via target protein blockade on tumor cells and targeted delivery of various therapeutic agents. In this review, we summarize recent advances in aptamer nanomaterials as targeted theranostic platforms for ovarian cancer and discusses the challenges and opportunities for their clinical application. The information presented in this review represents a valuable reference for creation of a new generation of aptamer nanomaterials for use in the precise detection and treatment of ovarian cancer.

Immunologically Effective Biomaterials.

Immunoregulation represents a booming field of biomaterial design. The unique physical and chemical properties of biomaterials offer tremendous opportunities for development. Each of their parameters exerts immunogenic effects at the immune system, cellular, and molecular levels. Herein, the perspective summarizes the interaction of biomaterials with immune cells and the underlying mechanisms to control immunoregulation in a top-down manner, providing solid inspiration for biomedical applications of immunologically effective biomaterials.