A new screening method for discovering antibacterial agents from filamentous fungi

Rapid development of resistance among major bacterial pathogens renders antibiotics more and more ineffective and it is crucial to find novel antibiotics for controlling these pathogens. Since high-throughput screening (HTS) that selects antibacterial agents according to targets in vitro rather than whole-cell have not proven effective in the discovery of new antibiotics; new approaches for discovering the next generation of antibiotics are urgently needed. Filamentous fungi are an important source for many of the antibiotics currently used, but screening them for novel antibiotics is difficult primarily due to the lack of efficient screening methods capable of maintaining whole bacterial cell metabolism. In this study, mixed agar plate culture (MAPC) screening method is described. The method maintains the advantages of traditional whole-cell screening but offers increased screening efficiency. Furthermore, its simplicity and convenience makes it suitable for many laboratories. MAPC screening increases the probability of discovering novel antibacterial agents from filamentous fungi under laboratory conditions.Keywords: Drug-resistant bacterial pathogens, novel antibiotics; screening method, filamentous fungi product

Cyclic Mechanical Stretching Induces Autophagic Cell Death in Tenofibroblasts Through Activation of Prostaglandin E2 Production

Background/Aims: Autophagic cell death has recently been implicated in the pathophysiology of tendinopathy. Prostaglandin E2 (PGE2), a known inflammatory mediator of tendinitis, inhibits tenofibroblast proliferation in vitro; however, the underlying mechanism is unclear. The present study investigated the relationship between PGE2 production and autophagic cell death in mechanically loaded human patellar tendon fibroblasts (HPTFs) in vitro. Methods: Cultured HPTFs were subjected to exogenous PGE2 treatment or repetitive cyclic mechanical stretching. Cell death was determined by flow cytometry with acridine orange/ethidium bromide staining. Induction of autophagy was assessed by autophagy markers including the formation of autophagosomes and autolysosomes (by electron microscopy, AO staining, and formation of GPF-LC3-labeled vacuoles) and the expression of LC3-II and BECN1 (by western blot). Stretching-induced PGE2 release was determined by ELISA. Results: Exogenous PGE2 significantly induced cell death and autophagy in HPTFs in a dose-dependent manner. Blocking autophagy using inhibitors 3-methyladenine and chloroquine, or small interfering RNAs against autophagy genes Becn-1 and Atg-5 prevented PGE2-induced cell death. Cyclic mechanical stretching at 8% and 12% magnitudes for 24 h significantly stimulated PGE2 release by HPTFs in a magnitude-dependent manner. In addition, mechanical stretching induced autophagy and cell death. Blocking PGE2 production using COX inhibitors indomethacin and celecoxib significantly reduced stretching-induced autophagy and cell death. Conclusion: Taken together, cyclic mechanical stretching induces autophagic cell death in tenofibroblasts through activation of PGE2 production

Treatment of Diabetic Foot with Autologous Stem Cells: A Meta-Analysis of Randomized Studies

Background. This meta-analysis was to evaluate the efficacy of autologous stem cell administration for the treatment of diabetic foot. Methods. The electronic databases included PubMed, EMBASE, BIOSIS, Cochrane central, and Google Scholar internet, last updated on May 30, 2019. Evaluated outcomes included the rate of wound healing and amputation. Dichotomous outcomes were described as risk ratios (RR) with 95% confidence intervals (CIs). Statistical analysis was performed with RevMan 5.0 software and STATA 10.0 software. Results. Eight randomized controlled trial (RCT) studies were included in this study. The meta-analysis showed a lower amputation (RR 0.25, 95% CI 0.11 to 0.54, I2=0) and a higher wound healing rate (RR 2.05, 95% CI 1.67 to 2.51, I2=4) in the cell therapy group compared with control. Conclusion. This meta-analysis supports the effective role of stem cell therapy in promoting wound healing and decreasing rate of amputation in diabetic foot. In the future, more high quality and well-designed studies are need

Impact of Microwave Treatment on Chemical Constituents in Fresh Rhizoma Gastrodiae (Tianma) by UPLC-MS Analysis

Fresh Rhizoma Gastrodiae (Tianma) was processed in a microwave oven at 2450 MHz in order to study the effect on the main chemical component changes taking place during microwave treatment. It was found that microwave affected the chemical composition of Tianma. Seven compounds, including gastrodin, gastrodigenin (p-hydroxybenzylalcohol), p-hydroxybenzaldehyde, vanillyl alcohol, vanillin, adenine, and 5-hydroxymethylfurfural, were identified in this study. As major active compounds, the contents of gastrodin and gastrodigenin in MWT Tianma were both twice as much as those in raw Tianma. Besides, the MS data show that there are still some unidentified compositions in Tianma, and there are also many converted compounds in MWT Tianma, which is worthy of further work. The results have indicated that microwave treated fresh Tianma might be helpful in designing the processing of traditional Chinese medicine and the application of microwave technology in traditional Chinese medicine needs to be researched further in the future

Protective effect of walnut on d‐galactose‐induced aging mouse model

OBJECTIVE(S) Accumulating evidence has suggested that oxidative stress and apoptosis are involved in the aging process. d‐galactose (gal) has been reported to cause symptoms of aging in mice, accompanied by liver and brain injuries. Our present work was to study the potential antioxidative and anti‐apoptotic effects of walnut and to explore how these effects act on mice in a d‐gal‐induced aging model. MATERIALS AND METHODS Aging mice were induced by subcutaneous injection of d‐gal (200 mg kg−1 d−1 for 8 weeks). Walnut samples were simultaneously administered to the d‐gal‐induced aging mice once daily by intragastric gavage. Finally, body weight, organ index, cognitive function, levels of antioxidative enzymes, and liver function were monitored. RESULTS The kernel pellicles of walnut could not only improve the learning and memory ability, and the organ index, but also significantly decrease body weight and normalize the levels of activity of antioxidative enzymes in aging mice. Further, the walnut seed coat would protect damages of hippocampus and liver in aging mice. HIGHLIGHTS In the current study, we investigated the effects of walnut kernels and walnut seed coats (WSCs) on d‐galactose‐induced aging mice. WSC was firstly found to have beneficial effects on d‐gal‐treated mouse's brain with learning and memory impairment, which probably through the underlying mechanism reduces oxidative damage and limits neuroinflammation. In addition, WSC had a protective effect on liver damage in d‐galactose sensing mice

Protective effect of walnut on d

OBJECTIVE(S) Accumulating evidence has suggested that oxidative stress and apoptosis are involved in the aging process. d‐galactose (gal) has been reported to cause symptoms of aging in mice, accompanied by liver and brain injuries. Our present work was to study the potential antioxidative and anti‐apoptotic effects of walnut and to explore how these effects act on mice in a d‐gal‐induced aging model. MATERIALS AND METHODS Aging mice were induced by subcutaneous injection of d‐gal (200 mg kg−1 d−1 for 8 weeks). Walnut samples were simultaneously administered to the d‐gal‐induced aging mice once daily by intragastric gavage. Finally, body weight, organ index, cognitive function, levels of antioxidative enzymes, and liver function were monitored. RESULTS The kernel pellicles of walnut could not only improve the learning and memory ability, and the organ index, but also significantly decrease body weight and normalize the levels of activity of antioxidative enzymes in aging mice. Further, the walnut seed coat would protect damages of hippocampus and liver in aging mice. HIGHLIGHTS In the current study, we investigated the effects of walnut kernels and walnut seed coats (WSCs) on d‐galactose‐induced aging mice. WSC was firstly found to have beneficial effects on d‐gal‐treated mouse's brain with learning and memory impairment, which probably through the underlying mechanism reduces oxidative damage and limits neuroinflammation. In addition, WSC had a protective effect on liver damage in d‐galactose sensing mice