Titanium carbide MXene-based hybrid hydrogel for chemo-photothermal combinational treatment of localized bacterial infection.

With the increased emergence and threat of multi-drug resistant microorganisms, MXenes have become not only an emerging class of two-dimensional functional nanomaterials, but also potential nanomedicines (i.e., antimicrobial agents) that deserve further exploration. Very recently, Ti3C2 MXene was observed to offer a unique membrane-disruption effect and superior light-to-heat conversion efficiency, but its antibacterial property remains unsatisfactory due to poor MXene-bacteria interactions, low photothermal therapy efficiency, and occurrence of bacterial rebound in vivo. Herein, the cationic antibiotic ciprofloxacin (Cip) is combined with Ti3C2 MXene, and a hybrid hydrogel was constructed by incorporating Cip-Ti3C2 nanocomposites into the network structure of a Cip-loaded hydrogels to effectively trap and kill bacteria. We found that the Cip-Ti3C2 nanocomposites achieved an impressive in vitro bactericidal efficiency of >99.99999% (7.03 log10) for the inhibition of methicillin-resistant Staphylococcus aureus (MRSA) by combining chemotherapy with photothermal therapy. In an MRSA-induced murine abscess model, the hybrid hydrogel simultaneously achieved high-efficiency sterilization and long-term inhibition effects, avoiding the rebound of bacteria after photothermal therapy, and thus maximized the in vivo therapeutic efficacy of Ti3C2 MXene-based systems. Overall, this work provides a strategy for efficiently combating localized bacterial infection by rationally designing MXene-based hybrid hydrogels. STATEMENT OF SIGNIFICANCE: Two-dimensional Ti3C2 MXene was recently regarded as a promising functional nanomaterial, however, its antibacterial applications are limited by the poor MXene-bacteria interactions, low photothermal therapy efficiency, and the occurrence of bacterial rebound in vivo. This work aims to construct a Ti3C2 MXene-based hybrid hydrogel for chemo-photothermal therapy and enhance the antimicrobial performance via a combination of the high-efficiency sterilization of ciprofloxacin-Ti3C2 nanocomposites with the long-term inhibition effect of ciprofloxacin hydrogel. The present study provides an example of efficient MXene-based antimicrobials to treat localized bacterial infection such as methicillin-resistant Staphylococcus aureus (MRSA)-induced skin abscess.

Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction.

BACKGROUND: Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. METHODS AND RESULTS: Eighteen adult mongrel male dogs were randomized into the control (n=8) and GPS (n=10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180-220bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. CONCLUSIONS: GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing.

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway.

In this study, we investigated the cardioprotective mechanisms of action of DT-010, a novel danshensu-tetramethylpyrazine conjugate. DT-010 significantly preserved cell viability and suppressed cell apoptosis in H9c2 cells injured by tert-butylhydroperoxide (t-BHP), iodoacetic acid (IAA) and hypoxia-reoxygenation. In addition, DT-010 pre-treatment reduced the intracellular level of free radicals including superoxide anion (·O2-), hydroxyl radical (·OH) and peroxynitrite anion (ONOO-) after t-BHP exposure. Moreover, DT-010 up-regulated the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear factor-E2-related factor 2 (Nrf2) as well as mitochondrial transcription factor A (Tfam) and heme oxygenase-1 (HO-1) in H9c2 cells. DT-010 also triggered Nrf2 nuclear translocation. In a rat myocardial ischemia-reperfusion model, DT-010 significantly alleviated myocardial infarction. The results indicated that DT-010 may be a promising candidate for the treatment of cardiovascular diseases, particularly myocardial ischemia and reperfusion injury.

Selective and sensitive determination of As(III) and tAs in Chinese herbal medicine samples using L-cysteine modified carbon paste electrode-based electrolytic hydride generation and AFS analysis.

A novel non-chromatographic speciation technique for ultra-trace arsenite [As(III)] and total arsenic (tAs) in Chinese herbal medicine (CHM) is developed and validated by electrolytic hydride generation (EHG) coupled with atomic fluorescence spectrometry (AFS). The studies show that As(III) can be converted efficiently to AsH3 on an L-cysteine modified carbon paste electrode (CMCPE), which has never been reported before. Significantly, other arsenic species such as arsenate [As(V)], monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) do not form any or only less volatile hydrides at low applied current mode (<1.0 A). The results also demonstrate that L-cysteine and graphite powder play different roles in the electrolytic generation of AsH3. Comparing with the traditional graphite electrode, CMCPE has better stability, sensitivity and interference tolerance. Under the optimal conditions, the limit of detection (LOD) of tAs and As(III) for this method are 0.087µgL-1 and 0.095µgL-1 respectively. The accuracy of the method is verified through the analysis of reference materials (CRM 08231 and SRM1568a), and the proposed method has been applied satisfactorily to the determination of As(III) and tAs in several CHM samples.