Local anesthetic lidocaine-encapsulated polymyxin-chitosan nanoparticles delivery for wound healing: in vitro and in vivo tissue regeneration.

In relieving local pains, lidocaine, one of ester-type local anesthetics, has been used. To develop the lidocaine membranes of enhanced local anesthetic effects, we have designed to establish the composition of wound dressings based on lidocaine chloride (LCH) (anesthetic drug)-loaded chitosan (CS)/polymyxin B sulfate (PMB). The LCH membranes (LCH-CS/PMB) was fabricated by the LCH oxide solutions within the CS/PMB matrix. The influences of different experimental limitations on CS/PMB membrane formations were examined. The double membrane particle sizes were evaluated by scanning electron microscopy (HR-SEM). Additionally, antibacterial efficacy was developed for gram-positive and negative microorganisms. Moreover, we examined in vivo healing of skin wounds formed in mouse models over 16 days. In contrast to the untreated wounds, rapid healing was perceived in the LCH-CS/PMB-treated wound with less damaging. These findings indicate that LCH-CS/PMB-based bandaging materials could be a potential innovative biomaterial for tissue repair and regeneration for wound healing applications in an animal model.

Midazolam inhibits proliferation and accelerates apoptosis of hepatocellular carcinoma cells by elevating microRNA-124-3p and suppressing PIM-1.

OBJECTIVE: Recently, the impact of microRNAs (miRNAs) has been identified in hepatocellular carcinoma (HCC), this study was designed to assess the effects of miR-124-3p and midazolam (MDZ) in HCC with the involvement of PIM-1. METHODS: HepG2 human HCC cells were selected for our study, which were treated with different concentrations of MDZ. The gain- and loss-of-function experiments were performed to elucidate the migration, invasion, proliferation, colony formation ability, cell cycle, and apoptosis of HepG2 cells upon treatment of MDZ, miR-124-3p mimics, or miR-124-3p inhibitor. The expression levels of miR-124-3p, PIM-1, Bax, Bcl-2, P21, and Ki-67 in HepG2 cells were assessed by reverse transcription quantitative polymerase chain reaction and western blot analysis. Moreover, HepG2 cell growth in vivo was measured by subcutaneous tumorigenesis in nude mice, and the target relation between miR-124-3p and PIM-1 was evaluated using dual luciferase reporter gene assay. RESULTS: We have found that after treated with overexpression of miR-124-3p and MDZ, there exhibited elevated miR-124-3p, declined expression of PIM-1, attenuated migration, invasion, proliferation and colony formation ability, and promoted apoptosis of HepG2 cells. Additionally, it could be observed that the tumor volume and weight were all reduced upon treatment of overexpression of miR-124-3p and MDZ. Meanwhile, the results in the HepG2 cells that treated with down-regulated miR-124-3p were the opposite. Furthermore, PIM-1 was found to be a target gene of miR-124-3p. CONCLUSION: Our study found that MDZ could inhibit proliferation and accelerate apoptosis of HCC cells by elevation of miR-124-3p and suppressing PIM-1, which may be an effective method in the treatment of HCC.

Vildagliptin inhibits high free fatty acid (FFA)-induced NLRP3 inflammasome activation in endothelial cells.

Elevated free fatty acids (FFAs) are a risk factor for type 2 diabetes. Endothelial dysfunction induced by high levels of FFAs is one of the mechanisms related to the progression of diabetes. In clinical diabetes care, DPP-4 inhibitors have been shown to be effective in reducing glucose levels. In this study, we investigated the molecular mechanism of the clinically available DPP-4 inhibitor vildagliptin in the protection of FFA-induced endothelial dysfunction. Treatment of endothelial cells with vildagliptin inhibits FFA-induced cellular LDH release and generation of ROS. Vildagliptin also reverses FFA-induced reduced levels of GSH and elevated expression of the FFA-associated NAPHD oxidase protein NOX-4. Moreover, vildagliptin ameliorates the reduction in mitochondrial potential triggered by FFAs. Mechanistically, we show that vildagliptin suppresses FFA-induced expression of proteins of the NLRP3 inflammasome complex, including NLRP3, ASC, p20 and HMGB-1, and mitigates FFA-induced inactivation of the AMPK pathway. Consequently, vildagliptin inhibits production of two cytokines that are favored by NLRP3 inflammasome machinery: IL-1ß and IL-18. Finally, we demonstrate that vildagliptin ameliorates FFA-induced reduced eNOS, indicating its protective role against endothelial dysfunction. Collectively, we conclude that the protective role of vildagliptin in endothelial cells is mediated via suppression of the AMPK-NLRP3 inflammasome-HMGB-1 axis pathway. These findings imply that the anti-diabetic drug vildagliptin possesses dual therapeutic applications in lowering glucose and improving vascular function.

Comparison of recovery effect for sufentanil and remifentanil anesthesia with TCI in laparoscopic radical resection during colorectal cancer.

The aim of the present study was to compare the recovery of sufentanil and remifentanil anesthesia by target-controlled infusion (TCI) in elderly patients with laparoscopic-assisted radical resection of colorectal cancer. The effect of anesthesia on patient stress response and cellular immune function was also observed. Elderly patients (n=192) who underwent laparoscopic radical resection of colorectal cancer between July 2014 and October 2015 were randomly divided into the sufentanil and remifentanil groups (n=96 per group). The two groups used sufentanil- and remifentanil-based anesthesia by TCI. The wake-up time, extubation time, orientation recovery time, vital signs, stress response, distribution of T-cell subsets and incidence of adverse reactions were recorded and compared. The wake-up and extubation times of the remifentanil group were significantly shorter than those of the sufentanil group. The difference of orientation recovery time was not statistically significant. The differences in heart rate, mean arterial pressure, and arterial oxygen saturation following anesthesia and during surgery and those prior to anesthesia of the sufentanil group were not statistically significant. However, those of the remifentanil group significantly improved following anesthesia. The concentrations of glucose, cortisol (COR), and interleukin-6 and C-reactive protein were stable in the sufentanil group, whereas the indices in the remifentanil group had a tendency of increasing during the anesthesia and surgery, and had a longer postoperative recovery time. The decreasing degree of T-cell subsets in the sufentanil group was significantly lower than that in the remifentanil group, and had a short recovery of cellular immunity following surgery. The adverse reactions rate during anesthesia of the remifentanil group was significantly higher than that of the sufentanil group. In conclusion, sufentanil- and remifentanil-based anesthesia with TCI has certain advantages, including improved recovery effect, less stress response, less inhibition of cellular immunity and fewer adverse reactions. It has the potential to become the first choice of anesthetic in the clinic for elderly patients who undergo laparoscopic radical resection for colorectal cancer.

Inactivation of INK4a and ARF induces myocardial proliferation and improves cardiac repair following ischemia­reperfusion.

The growth of the heart during mammalian embryonic development is primarily dependent on an increase in the number of cardiomyocytes (CM). However, shortly following birth, CMs cease proliferating and further growth of the myocardium is achieved via hypertrophic expansion of the existing CM population. The cyclin-dependent kinase inhibitor 2A (Cdkn2a) locus encodes overlapping genes for two tumor suppressor proteins, p16INK4a and p19 alternative reading frame (ARF). To determine whether decreased Cdkn2a gene expression results in improved cardiac regeneration in vitro and in vivo following cardiac injury, the proliferation of CMs isolated from Cdkn2a knockout (KO) and wild­type (WT) mice in vitro and in vivo were evaluated following generation of ischemia reperfusion (IR) injury. The KO mice demonstrated enhanced CM proliferation not only in vitro, but also in vivo. Furthermore, heart function was improved and scar size was decreased in the KO mice compared with that of the WT mice. The results also indicated that microRNA (miR)­1 and miR­195 expression levels associated with cell proliferation were reduced following IR injury in KO mice compared with those of WT mice. These results suggested that the inactivation of INK4a and ARF stimulated CM proliferation and promoted cardiac repair.