Decoding the role of the gut microbiome in gut-brain axis, stress-resilience, or stress-susceptibility: A review.

Increased exposure to stress is associated with stress-related disorders, including depression, anxiety, and neurodegenerative conditions. However, susceptibility to stress is not seen in every individual exposed to stress, and many of them exhibit resilience. Thus, developing resilience to stress could be a big breakthrough in stress-related disorders, with the potential to replace or act as an alternative to the available therapies. In this article, we have focused on the recent advancements in gut microbiome research and the potential role of the gut-brain axis (GBA) in developing resilience or susceptibility to stress. There might be a complex interaction between the autonomic nervous system (ANS), immune system, endocrine system, microbial metabolites, and bioactive lipids like short-chain fatty acids (SCFAs), neurotransmitters, and their metabolites that regulates the communication between the gut microbiota and the brain. High fiber intake, prebiotics, probiotics, plant supplements, and fecal microbiome transplant (FMT) could be beneficial against gut dysbiosis-associated brain disorders. These could promote the growth of SCFA-producing bacteria, thereby enhancing the gut barrier and reducing the gut inflammatory response, increase the expression of the claudin-2 protein associated with the gut barrier, and maintain the blood-brain barrier integrity by promoting the expression of tight junction proteins such as claudin-5. Their neuroprotective effects might also be related to enhancing the expression of brain-derived neurotrophic factor (BDNF) and glucagon-like peptide (GLP-1). Further investigations are needed in the field of the gut microbiome for the elucidation of the mechanisms by which gut dysbiosis contributes to the pathophysiology of neuropsychiatric disorders.

A stability-indicating LC–MS/MS method for zidovudine: Identification, characterization and toxicity prediction of two major acid degradation products / 药物分析学报

Zidvovudine (AZT) is a nucleoside analogue reverse transcriptase inhibitor (NRTI), a class of anti-retroviral drug. A stability-indicating assay method for AZT was developed in line with ICH guideline. Successful separation of AZT and its degradation products was achieved by gradient elution mode on reverse phase C18 column using 10 mM ammonium acetate: acetonitrile as the mobile phase at 0.8 mL/min flow rate, 25 μL injection volume, 30 °C column temperature and 285 nm detection wavelength. Two major acid degradation products were identified and characterized by liquid chromatography–electrospray ionization mass spectro-metry (LC–ESI/MS/MS) and accurate mass measurements. The probable mechanisms for the formation of degradation products were identified based on a comparison of the fragmentation pattern of the [M + H] + ions of AZT and its degradation products. One of the degradation products, DP-1, was isolated by semi-preparative high performance liquid chromatography (HPLC) using Waters XBridge Prep C18 (250 mm×10 mm, 5 μm). Degradation products showed higher toxicity compared to the drug in some models assessed by TOPKAT software. The method validation was performed with respect to robustness, specificity, linearity, precision and accuracy as per ICH guideline Q2 (R1).