Activity

Downregulation of circ-CCS inhibited lung cancer cell growth and metastasis while promoted apoptosis in vitro, and suppressed tumorigenesis of lung cancer in vivo. Circ-CCS had sponge effect on miR-383 and the function of si-circ-CCS was achieved by upregulating miR-383. E2F7 was a target gene of miR-383 and its downregulation was responsible for the anti-cancerous role of miR-383 in lung cancer. Circ-CCS could elevate E2F7 expression via interacting with miR-383.

Circ-CCS was shown to facilitate lung cancer progression via the miR-383/E2F7 axis, exhibiting the pivotal value of circ-CCS in diagnosis and treatment of lung cancer.

Circ-CCS was shown to facilitate lung cancer progression via the miR-383/E2F7 axis, exhibiting the pivotal value of circ-CCS in diagnosis and treatment of lung cancer.Topical photodynamic therapy (PDT) is widely used to treat non melanoma skin cancers. It consists of topically applying on the skin lesions a cream containing a prodrug (5-aminolevulinic acid (5-ALA) or methyl aminolevulinate (MAL)) that is then metabolized to the photosensitizer protoporphyrin IX (PpIX). Light irradiation at PpIX excitation wavelength combined with oxygen then lead to a photochemical reaction inducing cell death. Nevertheless, this conventional PDT treatment is currently restricted to superficial skin lesions since the penetration depth of the prodrug is limited and hampers the production of PpIX in deep seated lesions. To overcome this problem, dissolving microneedles (MNs) included in a square flexible patch were developed. This easy-to-handle MN-patch is composed of 5-ALA mixed with hyaluronic acid (HA) and has the ability to dissolve after skin application. To evaluate the efficiency of this MN-patch in vivo, a skin lesion model has been developed on rats by applying UV-B illuminations. After 40 UV-B illuminations, histological and pharmacokinetic controls confirmed that the rats presented skin lesions. Once the rat skin lesion model has been validated, it was demonstrated that the MNs penetrated into the skin and fully dissolved in one hour on most of the rats. After one hour, the fluorescence images showed that the MN-patch produced a consequent and homogeneous level of PpIX. Overall, the dissolving MN-patch is a recent technology that has interesting features and several preclinical investigations should be led to compare its efficiency to that of the conventional treatment for PDT of non melanoma skin cancers.Glycogen storage disease type Ia (GSD-Ia), deficient in glucose-6-phosphatase-α (G6PC), is characterized by impaired glucose homeostasis and a hallmark of fasting hypoglycemia. We have developed a recombinant adeno-associated virus (rAAV) vector-mediated gene therapy for GSD-Ia that is currently in a phase I/II clinical trial. While therapeutic expression of the episomal rAAV-G6PC clinical vector is stable in mice, the long-term durability of expression in humans is currently being established. Here we evaluated CRISPR/Cas9-based in vivo genome editing technology to correct a prevalent pathogenic human variant, G6PC-p.R83C. GSK1325756 CXCR antagonist We have generated a homozygous G6pc-R83C mouse strain and shown that the G6pc-R83C mice manifest impaired glucose homeostasis and frequent hypoglycemic seizures, mimicking the pathophysiology of GSD-Ia patients. We then used a CRISPR/Cas9-based gene editing system to treat newborn G6pc-R83C mice and showed that the treated mice grew normally to age 16 weeks without hypoglycemia seizures. The treated G6pc-R83C mice, expressing ≥ 3% of normal hepatic G6Pase-α activity, maintained glucose homeostasis, displayed normalized blood metabolites, and could sustain 24 h of fasting. Taken together, we have developed a second-generation therapy in which in vivo correction of a pathogenic G6PC-p.R83C variant in its native genetic locus could lead to potentially permanent, durable, long-term correction of the GSD-Ia phenotype.The development of microneedles (MNs) assisted drug delivery technologies have been highly active for more than two decades. The minimally invasive and self-administered MN technology bypasses many challenges associated with injectable drug delivery systems, by delivering the therapeutic materials directly into the dermal and ocular space and allowing the release of the active ingredient in a sustained or controlled manner. Different types of MNs (biodegradable solid/dissolving MNs and nanoparticle loaded/coated polymeric MNs or delivery by hollow MNs) have been envisioned for long-acting sustained delivery of therapeutic payloads, with the aim of reducing the side effects and administration frequency to improve the patient compliance. In this review, we covered the different types of MNs loaded with different nano/biotherapeutics for long-acting delivery for a wide range of potential clinical applications. We also outlined the future development scenario of such long-acting MN delivery systems for different disease conditions to achieve improved clinical benefit. Finally, we discussed the challenges lie ahead to realize the full potential of sustained-release long-acting MNs in the clinic.The present study aimed to investigate the effect of ghrelin on the degree of bursa of Fabricius (BF) fibrosis in infectious bursal disease virus-infected chickens. Specific pathogen free (SPF) chicks were divided into four groups. One group was used as the control (“C”). The other three groups were inoculated with IBDV on the 19th day, of which two were injected intraperitoneally with 0.5 nmol (“LG”) or 1.0 nmol (“HG”) ghrelin/100 g weight from the 18th day to the 22nd day, and one was injected intraperitoneally with PBS (“I”). Hematoxylin-eosin staining, Masson’s staining, and quantitative real-time PCR were used to determine the effects of ghrelin on the degree of inflammatory cell infiltration, the bursal fibrosis degree, and the expression of TGF-β and MMP-9 mRNA in IBDV-infected SPF chicks. The results showed that ghrelin administration reduced the number of infiltrated inflammatory cells in BF from 5 dpi and significantly attenuated the degree of fibrosis induced by IBDV from 2 dpi to 7 dpi (P less then 0.