IL-9 plays a critical role in helminth-induced protection against COVID-19-related cytokine storms.

A recent study published in mBio by Cao et al. demonstrated that the helminth Trichinella sprialis (Ts) alleviates COVID-19-related cytokine storms in an IL-9-dependent way (Z. Cao, J. Wang, X. Liu, Y. Liu, et al., mBio 15:e00905-24, 2024, https://doi.org/10.1128/mbio.00905-24). A cytokine storm is a severe immune response characterized by the overproduction of proinflammatory cytokines, such as TNF-α and IFN-γ, leading to tissue damage and mortality in COVID-19 patients. This study indicated that IL-9 is crucial in protecting against cytokine storm syndromes associated with SARS-CoV-2 infection and proposed that anti-inflammatory molecules from Ts excretory/secretory (TsES) products could be a novel source for treating such illnesses.

Usnea improves high-fat diet- and vitamin D3-induced atherosclerosis in rats by remodeling intestinal flora homeostasis.

Background: Usnea has various pharmacological properties, including anti-inflammatory, antitumor, antioxidant, antiviral, and cardiovasculoprotective effects. Aim of the study: To investigate the potential mechanisms underlying the anti-atherosclerosis (AS) activity of Usnea ethanol extract (UEE) via the regulation of intestinal flora. Materials and Methods: The chemical composition of UEE was determined using ultra-performance liquid chromatography with quadrupole exactive orbitrap mass spectrometry (UPLC-Q-EOMS). Thirty-six male Sprague-Dawley rats were divided into six groups. A high-fat diet and intraperitoneal vitamin D3 injections were used to establish a rat model of AS. After 4 weeks of treatment with UEE, hematoxylin-eosin staining was performed to evaluate the pathomorphology of the aorta, liver, and colon. The composition and diversity of the rat intestinal flora were determined using high-throughput 16S rRNA sequencing. Enzyme-linked immunosorbent assays were used to measure the levels of plasma trimethylamine oxide (TMAO), serum bile acid (BA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). The protein expression of cholesterol 7α-hydroxylase (CYP7A1) and flavin monooxygenase 3 (FMO3) in the liver and zonula occludens-1 (ZO-1) and occludin in colon tissue was detected via western blotting. Results: Forty-four compounds were identified in UEE. In the rat model of AS, UEE significantly prevented calcium deposition; decreased the serum levels of TC, TG, LDL-C, LPS, TNF-α, and IL-6; and increased the serum level of HDL-C. Additionally, all UEE dosages decreased the relative abundance of Verrucomicrobiota while increased that of Bacteroidetes. FMO3 protein expression and TMAO levels decreased, whereas CYP7A1 protein expression and BA levels increased. The absorption of intestinal-derived LPS was minimized. Furthermore, the protein expression of ZO-1 and occludin was upregulated. Conclusion: UEE ameliorated AS. The underlying mechanism was the reversal of imbalances in the intestinal flora by Usnea, thereby inhibiting calcium deposition, abnormal lipid metabolism, and inflammatory response.

Computational approach to decode the mechanism of curcuminoids against neuropathic pain.

BACKGROUND: Curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are the main components of turmeric that commonly used to treat neuropathic pain (NP). However, the mechanism of the therapy is not sufficiently clarified. Herein, network pharmacology, molecular docking and molecular dynamics (MD) approaches were used to investigate the mechanism of curcuminoids for NP treatment. METHODS: Active targets of curcuminoids were obtained from the Swiss Target database, and NP-related targets were retrieved from GeneCards, OMIM, Drugbank and TTD databases. A protein-protein interaction (PPI) network was built to screen the core targets. Furthermore, DAVID was used for GO and KEGG pathway enrichment analyses. Interactions between potential targets and curcuminoids were assessed by molecular docking and the MD simulations were run for 100ns to validate the docking results on the top six complexes. RESULTS: CUR, DMC, and BDMC had 100, 99 and 100 targets respectively. After overlapping with NP there were 33, 33 and 31 targets respectively. PPI network analysis of TOP 10 core targets, TNF, GSK3ß were common targets of curcuminoids. Molecular docking and MD results indicated that curcuminoids bind strongly with the core targets. The GO and KEGG showed that curcuminoids regulated nitrogen metabolism, the serotonergic synapse and ErbB signaling pathway to alleviate NP. Furthermore, specific targets in these three compounds were also analysed at the same time. CONCLUSIONS: This study systematically explored and compared the anti-NP mechanism of curcuminoids, providing a novel perspective for their utilization.

Marked Response of Rat Ileal and Colonic Microbiota After the Establishment of Alzheimer's Disease Model With Bilateral Intraventricular Injection of Aß (1-42).

Alzheimer's disease (AD) is a common neurodegenerative disease. More evidence has shown that gut microbiota is closely associated with AD. Also, studies have shown that the distribution of gut microbiota vary in different sections of the intestine. In this study, a rat model of AD was established using a bilateral intraventricular injection of ß-amyloid (1-42) [Aß (1-42)], and the behavior of rats, hippocampal Aß (1-42) deposition, and the ileal and colonic microbiota in each group were analyzed. We observed that the model rats had obvious memory and cognitive impairment, increased Aß (1-42) deposition, indicating that the AD model was successfully established. Through 16S rRNA-sequencing analysis, we found that α diversity, ß diversity, and dominant microbiota in the ileum and colon of normal rats were significantly different, showing spatial heterogeneity. Additionally, the surgery and injection of Aß (1-42) caused various degrees of disturbances in the ileal and colonic microbiota of rats. These findings provide new insights for the study of the gut microbiota of AD rats and help advance the development of therapeutic strategies for intervening AD through the gut microbiota.

Why can hydrothermally pretreating lignocellulose in low severities improve anaerobic digestion performances?

A lignocellulosic residue, rice straw, was hydrothermally pretreated for the whole slurry anaerobic digestion. In contrast to the unpretreated rice straw, 110-120 °C pretreatment promoted biogas yield by 35%-38%, while only 14% promotion happened on the pretreatment at 180 °C. To understand why this improvement happened at lower severities, the pretreated rice straw at 90 °C, 120 °C, and 180 °C were selected for the further investigation, in which the liquor and solid fraction were separated for digestion, and compared with the whole slurry digestion. Results indicated more methane was released from the derived liquor of 180 °C than that of 90 °C and 120 °C, however, solid fraction did not exhibit significantly different methane yields (187.77-193.91 mL/g TS). These results suggested that the released soluble fraction from pretreatment could facilitate the methanogenesis. Furthermore, the released inherent soluble fraction in rice straw was mainly responsible for higher biogas yield at lower temperatures. Pretreatment at higher temperatures disintegrated the rice straw recalcitrance more, and intensified the release of soluble fraction accordingly. Consequently, the methanogenesis of whole slurry could be promoted at the initial digestion; the hydrolysis/acidification of the solid fraction in whole slurry was weakened greatly, which resulted in a lower biogas yield. This can also be proved by the evolution of dominant bacteria and archaea in the anaerobic digestion of whole slurry, separated solid and liquor fraction.