Rochabranch2785

MicroRNAs (miRNAs) play crucial roles in maintaining normal physiological processes by regulating gene expression network and thus the tumor-suppressive miRNA has emerged as a promising antitumor agent for cancer treatment. However, targeted delivery of miRNA remains a challenge owing to its intrinsic macromolecular and negatively-charged features. Herein, we first employ the miRNA as crosslinker to construct a nucleic acid nanogel, in which miRNA is embedded and protected inside the three-dimensional (3D) nanostructure. Thereafter, nanobody (Nb) conjugated DNA (Nb-DNA) strands are further loaded on nanogel surface through nucleic acid hybridization, to form a Nb-functionalized nanogel (Nb-nanogel) for tumor-targeted miRNA delivery and antitumor treatment. Both in vitro and in vivo experiments show that nanogel equipped with Nb targeting moieties can greatly promote the miRNA accumulation at the tumor site and cellular uptake efficiency, resulting in significant improvement of the miRNA-mediated antitumor efficacy. this website This research provides a new approach for targeted miRNA delivery and may pave a new avenue to realize efficient miRNA replacement therapy for cancer treatment.With the prevalence of antibiotic-resistant bacteria, novel antibacterial strategies are urgently needed. In recent years, several antibiotics-independent physical approaches have attracted high attention and interests. Among those approaches, photothermal therapy (PTT), a novel non-invasive therapeutic technique, has exhibited great potentials in dealing with drug-resistant bacteria and bacterial biofilms. Photothermal agents (PTAs), which are either nanomaterials themselves or small molecules loaded in nanoparticles, are the essential element for PTT. How to deliver PTAs in a controlled manner is of great importance for high-efficiency and low-toxicity PTT. Therefore, a comprehensive understanding of various PTAs is required for the better application of PTT in antibacterial treatment. Herein, the physicochemical properties and antibacterial PTT of five types of PTAs are summarized. In addition, the PTT-involved multifunctional theranostics nanoplatforms and the potential approaches for reducing the side effects of PTT (such as targeted delivery and controlled release of PTAs) are also discussed.Development of injectable nanoparticles for delivery of active anticancer compounds often requires complicated schemes that involve tedious synthetic protocols and nanoformulations. In particular, clinical translation of synergistic nanoparticles that can facilitate multimodal therapies remains a considerable challenge. Herein, we describe a self-assembling, small-molecule nanosystem with unique properties, including near-infrared (NIR) light-responsive drug activation, size transformability, combinatorial synergy, and substantially reduced toxicity. Ligation of anticancer cabazitaxel (CTX) drugs via a reactive oxygen species-activatable thioketal linkage generates a dimeric TKdC prodrug, and subsequent coassembly with a photosensitizer, chlorin e6 (Ce6), forms colloidal-stable nanoassemblies (termed psTKdC NAs). Upon NIR laser irradiation, psTKdC NAs are transformed into smaller size particles and facilitate production of pharmacologically active CTX. Importantly, reactive oxygen species yielded by coassembled Ce6 can synergize with chemotherapy to achieve potent combinatorial effects. In a preclinical orthotopic model of an aggressive, human melanoma patient-derived xenograft (PDX), we show that administration of psTKdC NAs followed by laser irradiation produced durable tumor regression, with the tumors being completely eradicated in three of six PDXs. Furthermore, low systemic toxicity of this smart, photo-activatable nanotherapy was observed in animals. The new self-deliverable combinatorial system addresses essential requirements for high efficacy, safety, and translational capacity and deserves further investigation.The main purpose of this study was to evaluate the estrogenic properties of total flavonoids (TFs) and five flavonoid monomers (cardamonin (Car), pinostrobin chalcone (PC), wogonin (Wo), chrysin (Chr) and Pinocembrin (PI)) from leaves of Carya cathayensis Sarg (LCC). TFs from LCC were isolated and determined using HPLC. The 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were performed to assess the effects of flavonoids on cell proliferation and cell cycle, respectively. The molecular docking technique was applied to investigate binding conformations of the monomers from LCC to the estrogen receptor ERα and ERβ. Gene and protein expression patterns were assessed using quantitative real-time PCR (qRT-PCR) and western blot, respectively. The results showed that TFs, Car, PC, Wo and Chr promoted proliferation of MCF-7 cells and cell transition from the G1 to S phase, and inhabitation of MCF-7 cell proliferation was observed after the treatment of PI. Molecular docking studies confirmed ERs as molecular targets for the monomers. TFs, Car, PC, Wo and Chr from LCC promoted gene expression of ERα, ERβ, progesterone receptor (PR) and pS2. Our collective results demonstrated that TFs and monomers from LCC may exert ER agonist activity through competitively bind to ER, inducing ER upregulation and active ER to estrogen response element (ERE)- independent gene regulation. As an abundant natural product, LCC may provide a novel medicinal source for treatment of diseases caused by estrogen deficiency.Phytochemical analysis of the fruits of Raphia vinifera led to the isolation of four new steroidal saponins (1-4), along with six known secondary metabolites (6-10). The structures of the isolated compounds were determined based on the analyses of NMR and mass spectrometric data, and chemical degradation reactions. Among the compounds tested, 1 and 4 showed the most promising cytotoxic activity against the drug-sensitive CCRF-CEM leukemia cell lines, with IC50 values of 3.55 µM and 7.14 µM, respectively.Tolosa-Hunt syndrome is a rare disorder characterized by granulomatous inflammation involving the cavernous sinus, superior orbital fissure, and/or orbit with no additional underlying cause. Tolosa-Hunt syndrome most often presents with painful ophthalmoplegia involving one or multiple cranial nerves. Here we report the case of an 8-year-old girl who presented, atypically, without the hallmark finding of pain. This case of pediatric Tolosa-Hunt syndrome is the only reported example to date lacking what is considered its pathognomonic feature and thus brings to light the clinical variability of this already inconspicuous disorder.