Effects of Malate Ringer's solution on myocardial injury in sepsis and enforcement effects of TPP@PAMAM-MR.

BACKGROUND: Myocardial dysfunction played a vital role in organ damage after sepsis. Fluid resuscitation was the essential treatment in which Lactate Ringer's solution (LR) was commonly used. Since LR easily led to hyperlactatemia, its resuscitation effect was limited. Malate Ringer's solution (MR) was a new resuscitation crystal liquid. Whether MR had a protective effect on myocardial injury in sepsis and the relevant mechanism need to be studied. METHODS: The cecal ligation and puncture (CLP) inducing septic model and lipopolysaccharide (LPS) stimulating cardiomyocytes were used, and the cardiac function, the morphology and function of mitochondria were observed. The protective mechanism of MR on myocardial injury was explored by proteomics. Then the effects of TPP@PAMAM-MR, which consisted of the mitochondria- targeting polymer embodied malic acid, was further observed. RESULTS: Compared with LR, MR resuscitation significantly prolonged survival time, improved the cardiac function, alleviated the damages of liver, kidney and lung following sepsis in rats. The proteomics of myocardial tissue showed that differently expressed proteins between MR and LR infusion involved oxidative phosphorylation, apoptosis. Further study found that MR decreased ROS, improved the mitochondrial morphology and function, and ultimately enhanced mitochondrial respiration and promoted ATP production. Moreover, MR infusion decreased the expression of apoptosis-related proteins and increased the expression of anti-apoptotic proteins. TPP@PAMAM@MA was a polymer formed by wrapping L-malic acid with poly amido amine (PAMAM) modified triphenylphosphine material. TPP@PAMAM-MR (TPP-MR), which was synthesized by replacing the L-malic acid of MR with TPP@PAMAM@MA, was more efficient in targeting myocardial mitochondria and was superior to MR in protecting the sepsis-inducing myocardial injury. CONCLUSION: MR was suitable for protecting myocardial injury after sepsis. The mechanism was related to MR improving the function and morphology of cardiomyocyte mitochondria and inhibiting cardiomyocyte apoptosis. The protective effect of TPP-MR was superior to MR.

Integrated analysis reveals important differences in the gut and oropharyngeal microbiota between children with mild and severe hand, foot, and mouth disease.

Little is known about alternation and difference in gut microbiota between patients with mild and severe hand, foot, and mouth disease (HFMD). We investigated the differences in gut and oropharynx microbiota between mild and severe HFMD in young children and changes in bacterial profiles as the disease progresses from acute to convalescent phase. Forty-two patients with confirmed HFMD were studied, among which 32 had severe HFMD and 10 had mild HFMD. First rectal swabs were collected from all patients at an average of 2 days (acute phase) after the onset of symptoms, and second rectal swabs were collected from 8 severe patients at day 9 (convalescent phase) after the onset. Oropharyngeal swabs were obtained from 10 patients in the acute phase and 6 in the convalescent phase. 16S rRNA sequencing was performed for all 70 samples. Compared with mild HFMD, severe HFMD exhibited significantly decreased diversity and richness of gut microbiota. Gut microbiota bacterial profiles observed in the acute and convalescent phases resembled each other but differed from those in mild cases. Additionally, 50% of patients with severe HFMD in the acute phase harboured a dominant pathobiontic bacterial genus. However, none of the patients with mild HFMD had such bacteria. Similar bacterial compositions in oropharynx microbiota were detected between mild and severe cases. Our findings indicate that severe HFMD exhibits significantly impaired diversity of gut microbiota and frequent gut and oropharyngeal inflammation-inducing bacteria. However, the results should be interpreted with caution as the number of subjects was limited.

A novel elastic liposome for skin delivery of papain and its application on hypertrophic scar.

This study aims to investigate the therapeutic effects of papain elastic liposomes (PEL) on hypertrophic scar through topical application. PEL were prepared using the reverse-phase evaporation method and optimized by response surface methodology. The transdermal absorption of optimized PEL was tested by vertical Franz diffusion cells in vitro. The effects of PEL were investigated in rabbit model of hypertrophic scar in vivo, histological analysis and scar-related proteins were detected to reveal potential scar repair mechanism. The best formulation of PEL had EE (43.8±1.4%), particle size (100.9±2.2nm), PDI (0.037±0.003), zeta potential (-26.3±1.3mV), and DI (21.9±3.1). PEL gave the cumulative amounts and steady state fluxes in the receiver solution of 381.9±32.4µg/cm2, 11.4±1.5µg/cm2/h, and showed drug deposition in skin of 19.1±3.2% after 24h. After topical application, the scar elevation index, microvascular density, and collagen fiber were significantly decreased with regular arrangement. The expressions of TGF-ß1, P-Smad-3, P-NF-κB p65, and P-IKBa in hypertrophic scar were significantly down regulated in contrast with those in model group. PEL were proven as an excellent topical preparation for hypertrophic scar treatment.

Electropolymerized multiwalled carbon nanotubes/polypyrrole fiber for solid-phase microextraction and its applications in the determination of pyrethroids.

A novel solid-phase microextraction (SPME) fiber coated with multiwalled carbon nanotubes/polypyrrole (MWCNTs/Ppy) was prepared with an electrochemical method and used for the extraction of pyrethroids in natural water samples. The results showed that the MWCNTs/Ppy coated fiber had high organic stability, and remarkable acid and alkali resistance. In addition, the MWCNTs/Ppy coated fiber was more effective and superior to commercial PDMS and PDMS/DVD fibers in extracting pyrethroids in natural water samples. Under optimized conditions, the calibration curves were found to be linear from 0.001 to 10 µg mL(-1) for five of the six pyrethroids studied, the exception being fenvalerate (which was from 0.005 to 10 µg mL(-1)), and detection limits were within the range 0.12-0.43 ng mL(-1). The recoveries of the pyrethroids spiked in water samples at 10 ng mL(-1) ranged from 83 to 112%.