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Keywords: Hepatitis B virus; Acute-on-chronic liver failure; Prognosis EN Hepatitis B virus Acute-on-chronic liver failure Prognosis 479 480 2 12/30/20 20210201 NES 210201 To the Editor: We read the paper "The PREDICT study uncovers three clinical courses in acutely decompensated cirrhosis with distinct pathophysiology" published in Journal of Hepatology with great interest.[1] This multicenter study reported on 3 different clinical courses with distinct pathophysiology and prognosis in patients with acute decompensation (AD) of cirrhosis. Clinical and laboratory characteristics of the pre-ACLF patients (n = 90), ACLF patients at the time of admission (n = 189) and patients with AD without ACLF development (n = 587) were compared in Table 1. The prevalence of HBV reactivation was different (p <0.001) among these patients and higher in pre-ACLF patients (56.7%) and ACLF patients (57.7%). [Extracted from the article]

Intestinal pathophysiological alterations have recently been revealed to be implicated in the pathogenesis of hypertension, necessitating further investigations to better understand the intestinal effects of anti-hypertensive drugs. The current study thus investigated the pharmacological implications of a commonly used first-line angiotensin II type 1 receptor blocker, candesartan cilexetil, on the intestinal barrier impairment and gut dysbiosis in spontaneously hypertensive rats (SHRs). The results revealed that candesartan treatment protected against ileal and colonic pathologies and increased the intestinal expression of genes encoding tight junction proteins such as cingulin, occludin and tight junction protein 1 in SHRs. Serum level of lipopolysaccharides-binding protein was increased in candesartan-treated SHRs, supporting the notion that candesartan treatment provided protection against hypertension-associated impairment of intestinal barrier. Candesartan treatment also increased the amount of fecal short-chain fatty acids (SCFAs) including acetic acid, propionic acid, and butyric acid in SHRs. Fecal 16S rDNA sequencing further revealed that candesartan treatment normalized hypertension-altered ratio of Firmicutes to Bacteroidete s in SHRs. Most notably, candesartan treatment counteracted hypertension-associated diminishment of lactic acid-producing genus Lactobacillus. Taken together, the current study demonstrates for the first time that candesartan treatment alleviates hypertension-associated pathophysiological alterations in the gut, increases microbial production of SCFAs and preserves gut Lactobacillus under hypertensive conditions, which sheds novel light on the pharmacological implications of candesartan in the treatment of hypertension. [ABSTRACT FROM AUTHOR]

Structural plasticity and dynamic protein–protein interactions are critical determinants of protein function within living systems. Quantitative chemical cross-linking with mass spectrometry (qXL-MS) is an emerging technology able to provide information on changes in protein conformations and interactions. Importantly, qXL-MS is applicable to complex biological systems, including living cells and tissues, thereby providing insights into proteins within their native environments. Here, we present an overview of recent technological developments and applications involving qXL-MS, including design and synthesis of isotope-labeled cross-linkers, development of new liquid chromatography–MS methodologies, and computational developments enabling interpretation of the data. [Display omitted] • Quantitative chemical cross-linking provides information on changes in protein interactomics. • Overview of recent technological developments involving qXL-MS. • Applications of qXL-MS in biological systems with varying conditions. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury can lead to activation of spinal microglia, which can mediate neuroinflammation and contribute to neuropathic pain following nerve injury. Activated microglia may manifest with either pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype, which may lead to detrimental or beneficial roles in the nervous system. In this study, microglia numbers, morphology and gene profiles were examined in the dorsal spinal cord of rats over 14 days following sciatic nerve chronic constriction injury (CCI). The morphology of some microglia changed from a surveying to an activated state within 1 day of CCI. Neuropathic pain developed within seven to 14 days following injury and microglia numbers were increased, with almost all in the dorsal spinal cord morphologically defined as activated. At day one after CCI, both M1 and M2 microglia-related genes were increased but only M1 microglia-related genes remained elevated at day seven and 14 thereafter. These results indicate that both M1 and M2 microglia were activated in the dorsal spinal cord one day after CCI but the microglia skewed towards M1 phenotype during the following seven and 14 days. [ABSTRACT FROM AUTHOR]