Quinomycins with an unusual N-methyl-3-methylsulfinyl-alanine residue from a Streptomyces sp.

Four new echinomycin congeners, quinomycins M-P (1-4) were isolated from the cultures of the soil-derived Streptomyces sp. CPCC205575. The planar structures were determined by comprehensive analyses of NMR and HRESIMS/MS data. The absolute configurations were elucidated by the advanced Marfey's method combined with biosynthetic gene analysis. Compounds 1-4 represent the first examples of quinomycin-type natural products with the sulfur atom at the N,S-dimethylcysteine residue oxidized as a sulfoxide group forming the unusual N-methyl-3-methylsulfinyl-alanine residue. Bioassay results revealed that the oxidation of the sulfur atom at the Cys or Cys' residues led to dramatic decrease of cytotoxicity and antimicrobial activity.

Anti-Biofilm Activity of Cocultimycin A against Candida albicans.

Candida albicans (C. albicans), the most common fungal pathogen, has the ability to form a biofilm, leading to enhanced virulence and antibiotic resistance. Cocultimycin A, a novel antifungal antibiotic isolated from the co-culture of two marine fungi, exhibited a potent inhibitory effect on planktonic C. albicans cells. This study aimed to evaluate the anti-biofilm activity of cocultimycin A against C. albicans and explore its underlying mechanism. Crystal violet staining showed that cocultimycin A remarkably inhibited biofilm formation in a dose-dependent manner and disrupted mature biofilms at higher concentrations. However, the metabolic activity of mature biofilms treated with lower concentrations of cocultimycin A significantly decreased when using the XTT reduction method. Cocultimycin A could inhibit yeast-to-hypha transition and mycelium formation of C. albicans colonies, which was observed through the use of a light microscope. Scanning electron microscopy revealed that biofilms treated with cocultimycin A were disrupted, yeast cells increased, and hypha cells decreased and significantly shortened. The adhesive ability of C. albicans cells treated with cocultimycin A to the medium and HOEC cells significantly decreased. Through the use of a qRT-PCR assay, the expression of multiple genes related to adhesion, hyphal formation and cell membrane changes in relation to biofilm cells treated with cocultimycin A. All these results suggested that cocultimycin A may be considered a potential novel molecule for treating and preventing biofilm-related C. albicans infections.

A Mitochondrial Perspective on Noncommunicable Diseases.

Mitochondria are the center of energy metabolism in eukaryotic cells and play a central role in the metabolism of living organisms. Mitochondrial diseases characterized by defects in oxidative phosphorylation are the most common congenital diseases. Meanwhile, mitochondrial dysfunction caused by secondary factors such as non-inherited genetic mutations can affect normal physiological functions of human cells, induce apoptosis, and lead to the development of various diseases. This paper reviewed several major factors and mechanisms that contribute to mitochondrial dysfunction and discussed the development of diseases closely related to mitochondrial dysfunction and drug treatment strategies discovered in recent years.

Nitric oxide alleviates salt stress in seed germination and early seedling growth of pakchoi (Brassica chinensis L.) by enhancing physiological and biochemical parameters.

The germination and seedling vigor of crops is negatively affected by soil salinity. Nitric oxide (NO) has emerged as a key molecule involved in many physiological events in plants. The objective of present study was to evaluate the impact of exogenous sodium nitroprusside (SNP, a NO donor) at different concentrations on the seed germination and early seedling growth characteristics of pakchoi (Brassica chinensis L.) under NaCl stress. 100 mM NaCl stress markedly inhibited the seed germination potential, germination index, vitality index and growth of radicles and plumules. SNP pretreatment attenuated the salt stress effects in a dose-dependent manner, as indicated by enhancing the characteristics of seed germination and early seedling growth parameters, and the mitigating effect was most pronounced at 10 µM SNP. Efficient antioxidant systems were activated by SNP pre-treatment, and which effectively increased the activities of superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX), and reduced contents of malondialdehyde (MDA) and hydrogen peroxide (H2O2) and the production rate of superoxide anion radical (O2·-) in radicles and plumules, thereby preventing oxidative damage from NaCl stress. SNP pre-treatment also increased the contents of proline and soluble sugar in radicles and plumules under NaCl stress. In addition, SNP pre-treatment significantly increased the K+ contents and decreased Na+ contents in radicles and plumules, resulting in the increased level of K+/Na+ ratio. Our results demonstrated that SNP application on pakchoi seeds may be a good option to improve seed germination and seedling growth under NaCl stress by modulating the physiological responses resulting in better seed germination and seedling growth.