Fatigue and sleep quality in Chinese adults with connective tissue disease: A cross-sectional study.

OBJECTIVES: This study aims to evaluate fatigue and sleep quality among adults with connective tissue disease (CTD), and the interrelationship. METHODS: From April 2020 to February 2021, adult CTD patients hospitalized were invited to complete sociodemographic and disease-related data, Fatigue Severity Scale (FSS), and Pittsburgh Sleep Quality Index (PSQI), as well as laboratory detection through computer query. Statistical analysis was performed using SPSS 22.0. RESULTS: A total of 363 patients with CTD were included in the study. Of which, 313 patients were accompanied by single CTD (systemic lupus erythematosus (SLE) = 109, Sjogren's syndrome (SS) = 51, rheumatoid arthritis (RA) = 44, idiopathic inflammatory myopathies (IIM) = 36, Vasculitis = 17, systemic sclerosis (SSc) = 14, other = 42, respectively), and 50 patients had CTD ≥ 2. Compared with CTD = 1, patients with CTD ≥ 2 had longer disease duration, higher erythrocyte sedimentation rate, and higher IgG level (all P < 0.05). The prevalence of poor sleep quality in 363 CTD patients was 61.2%, among which, 59.1% for CTD = 1 and 74.0% for CTD ≥ 2, with significant difference (P = 0.045). Additionally, 75.5% experienced fatigue, and 75.4% for CTD = 1, 76.0% for CTD ≥ 2 (P = 0.927). Fatigue and sleep quality interacted in CTD patients (r = 0.236, P < 0.01; χ2 = 11.302, P = 0.001). Interestingly, no significant differences were found in the prevalence of fatigue and poor sleep quality among CTD subgroups, as well as the FSS score, the seven components of sleep quality and total PSQI score (P > 0.05). CONCLUSIONS: More than 3/5 CTD patients experience fatigue and poor sleep quality, and not different among CTD subgroups. Targeted interventions are needed to reduce fatigue, improve sleep quality, and ultimately improve the prognosis of patients with CTD.

Identification of potential immunomodulators from Pulsatilla decoction that act on therapeutic targets for ulcerative colitis based on pharmacological activity, absorbed ingredients, and in-silico molecular docking.

BACKGROUND: Pulsatilla decoction (Bai-Tou-Weng-Tang, BTWT) is a classic formula prescription of a traditional Chinese medicine that is used to treat ulcerative colitis (UC). However, its active components and underlying mechanism of action remain unclear. In the present study, we aimed to identify potential immunomodulators from BTWT that act at therapeutic targets for UC. METHODS: The protective effects of BTWT granules were examined in mice with colitis induced by dextran sulfate sodium. The absorbed components of BTWT were identified using LC-MS, and selected protein targets of these components in UC were investigated using molecular docking. RESULTS: Oral administration of BTWT granules significantly alleviated disease severity and colon shortening, and inhibited the inflammatory response in mice with chronic colitis. In these mice, 11 compounds from the BTWT granules were detected in the serum and/or colon. The molecular docking study demonstrated that compounds from Radix pulsatillae, such as anemoside A3, interacted with STAT3 and S1PR1; compounds from Rhizoma coptidis and/or Cortex phellodendri, such as palmatine, interacted with JAK3, PD-1, and PD-L1; and components of Cortex fraxini such as aesculin interacted with S1PR1, JAK3, STAT3 and PD-L1. Further in-vitro experiments showing that the compounds inhibited TNF-α and IL-6 production and STAT3 activation in RAW 264.7 cells suggested that these compounds have immunomodulatory activities. CONCLUSION: We revealed for the first time that 11 absorbed ingredients from BTWT were immunomodulators against therapeutic targets for UC. These findings suggest that the identified compounds are the active components of BTWT, and the identified protein targets underlie the mechanism of action of BTWT against UC.

Anemoside B4 ameliorates experimental autoimmune encephalomyelitis in mice by modulating inflammatory responses and the gut microbiota.

BACKGROUND: Anemoside B4 (AB4) is a representative component of Pulsatilla decoction that is used in traditional Chinese medicine for treating inflammatory conditions. It is not known whether AB4 has beneficial effects on multiple sclerosis (MS). METHODS: In the present study, we examined the preventative and therapeutic effects of AB4, and the possible mechanism by which it protects female mice against experimental autoimmune encephalomyelitis (EAE). RESULTS: Preventative treatment with AB4 (given orally at 100 and 200 mg/kg for 18 days) reduced the clinical severity of EAE significantly (from 3.6 ± 1.3 to 1.8 ± 1.5 and 1.6 ± 0.6, respectively), and inhibited demyelination and inflammatory infiltration of the spinal cord. In the therapeutic protocol, oral administration of 200 mg/kg AB4 for 21 days after initiation of EAE significantly alleviated disease severity (from 2.6 ± 1.3 to 0.9 ± 0.6) and was as effective as the clinically used drug fingolimod (0.3 ± 0.6). Furthermore, both doses of AB4 significantly inhibited mRNA expression of TNF-α, IL-6, and IL-17, and STAT3 activation, in the spinal cord; and the ex vivo and iv vitro AB4 treatment markedly inhibited secretion of the three cytokines from lymphocytes of EAE mice upon in vitro restimulation. In addition, AB4 reversed the changes in the composition of the intestinal microbiome observed in EAE mice. CONCLUSION: We reveal for the first time that AB4 protects against EAE by modulating inflammatory responses and the gut microbiota, demonstrating that AB4 may have potential as a therapeutic agent for treating MS in humans.

Anemoside B4 protects against chronic relapsing colitis in mice by modulating inflammatory response, colonic transcriptome and the gut microbiota.

BACKGROUND: Anemoside B4 (AB4) is reported to prevent acute colitis when given via intraperitoneal injection by two recent studies. However, whether oral AB4 protects against chronic colitis which resembles the clinical phenotype of ulcerative colitis (UC) and its mechanism of action are largely unknown. PURPOSE: To systemically investigate the effects of oral AB4 against chronic colitis and illustrate the underlying mechanism of action. METHODS: The preventive, therapeutic, and dose-dependent effects of AB4 against UC were examined in mice with acute or chronic relapsing colitis induced by dextran sulfate sodium (DSS). The inflammatory responses, colonic transcriptome, and 16S rDNA sequencing of the intestinal content of mice were analyzed. RESULTS: Oral administration of AB4 alleviated disease severity and colon shortening in mice with chronic relapsing colitis in a dose-dependent manner. The effects of AB4 were comparable to those of two positive-control compounds: tofacitinib and berberine. Unlike tofacitinib, AB4 did not have a deleterious effect on DSS-induced splenic swelling and anemia. Furthermore, AB4 inhibited the inflammatory responses of colitis, as evidenced by in-vivo, ex-vivo, and in-vitro studies. Transcriptomics revealed that AB4 treatment reversed the DSS-mediated decrease in the expression of colonic Pelo, B3gat2 and Mir8010. In addition, AB4 reversed DSS-induced alterations in the intestinal microbiome in mice. Through fecal microbiota transplantation, we proved that AB4 partially exerted its anti-colitis effects by modulating the gut microbiota. CONCLUSIONS: We demonstrated for the first time that AB4 has dose-dependent therapeutic effects against chronic relapsing colitis by modulating the inflammatory response, colonic gene expression, and intestinal microbiota.