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Autism spectrum disorder (ASD) and schizophrenia have a genetic basis, but environmental factors also play a significant role in their etiopathogenesis. One of them may be an infectious disease in the mother during pregnancy. This is indicated mainly by the epidemiological studies, in which a prenatal infection has been shown to increase under certain circumstances the risk of ASD and schizophrenia in the offspring. Animal experiments indicate that the immune response of the mother plays a key role here, especially in the form of a cytokine storm. However, the resulting effect of the prenatal infection depends on several risk and protective factors on the side of the mother and the fetus, as well as on the characteristics of the infections. In case of COVID-19, due to the shortness of time, such studies are absent, however, due to its infectious nature, and predominantly its high prevalence rates, it is reasonable to consider this disease as a potential risk. The objective of our paper was to summarize results of epidemiological and animal studies in respect to other infections and, based on that, to analyse whether COVID-19 during pregnancy represents a risk for the development of ASD or schizophrenia in the offspring. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cachexia is a multifactorial condition characterized by body weight loss and skeletal muscle wasting that negatively impacts the quality of life and survival of cancer patients. In this paper, we found that ursolic acid (UA) alleviated cancer cachexia and prevented muscle wasting via activating SIRT1, and thence inhibiting phosphorylation levels of NF-κB and STAT3. Furthermore, UA remained effective in the advanced stages of cancer cachexia. This is significant because no approved drug for the treatment of cancer-related muscle atrophy is available. UA may be a potential drug for cancer cachexia and has the possibility of translational application to clinical treatment. Skeletal muscle wasting is the most remarkable phenotypic feature of cancer cachexia that increases the risk of morbidity and mortality. However, there are currently no effective drugs against cancer cachexia. Ursolic acid (UA) is a lipophilic pentacyclic triterpene that has been reported to alleviate muscle atrophy and reduce muscle decomposition in some disease models. This study aimed to explore the role and mechanisms of UA treatment in cancer cachexia. We found that UA attenuated Lewis lung carcinoma (LLC)-conditioned medium-induced C2C12 myotube atrophy and muscle wasting of LLC tumor-bearing mice. Moreover, UA dose-dependently activated SIRT1 and downregulated MuRF1 and Atrogin-1. Molecular docking results revealed a good binding effect on UA and SIRT1 protein. UA rescued vital features wasting without impacting tumor growth, suppressed the elevated spleen weight, and downregulated serum concentrations of inflammatory cytokines in vivo. The above phenomena can be attenuated by Ex-527, an inhibitor of SIRT1. Furthermore, UA remained protective against cancer cachexia in the advanced stage of tumor growth. The results revealed that UA exerts an anti-cachexia effect via activating SIRT1, thereby downregulating the phosphorylation levels of NF-κB and STAT3. UA might be a potential drug against cancer cachexia. [ABSTRACT FROM AUTHOR]

The aim of this paper was to explore the mechanism of bladder meridian massage (BMM) on anxiety in rats with chronic stress. Chronic stress induced rats to establish rat anxiety model. The sugar water preference (SPF), tail suspension time (TST), and forced swimming time (FST) of rats were measured. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines in serum and hippocampus of rats were detected. Brain neurotransmitters (dopamine (DA), 5- hydroxytryptamine (5-HT), and norepinephrine (NE)) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Immunohistochemistry and western blotting were used to detect autophagy protein expression in hippocampus of rats. BMM significantly increased SPF, decreased TST and FST, increased SOD level in serum and hippocampus, and decreased MDA level and cytokine level. BMM reversed the changes of neurotransmitters. At the same time, BMM significantly decreased autophagy protein expression in hippocampus of rats. The above results show that BMM significantly relieve anxiety induced by chronic stress in rats. [ABSTRACT FROM AUTHOR]

Background. Depression is a major cause of disability and most antidepressant medicines are ineffective owing to their high toxicity and numerous adverse effects. As a result, there is an urgent need to find new effective treatment methods. This paper aims to investigate the effect and mechanism of total saikosaponins (TSS) on depression-like behaviors induced by chronic unpredictable mild stress (CUMS) in rats. Methods. Twenty-four male SD rats were randomly divided into 4 groups: control group, CUMS group, TSS group, and fluoxetine (Flu) group. Then, the following tests were conducted: sucrose preference test, open field test, and elevated plus maze test. Additionally, ELISA was used to detect the levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH) in the serum of the rats as well as the levels of inflammatory cytokines IL-1β, IL-6, and TNF-α in the hippocampus, and Western blot was used for measuring the expression of brain-derived neurotrophic factor (BDNF) protein and related proteins of the PI3K/AKT/NF-κB signaling pathway in the hippocampus. Results. TSS could significantly improve rat behaviors, specifically indicated by increases in sucrose preference, total movement distance, stay time in the central area, number of entries into open arms, time spent in open arms, and a decrease in stay time in the peripheral area. TSS acted to significantly reduce BDNF protein expression and increase the contents of ACTH and CORT in serum as well as the levels of IL-1β, IL-6, and TNF-α in the hippocampal tissue in rats. In addition, it was able to raise the ratios of p-PI3K/PI3K and p-AKT/AKT and decrease the ratio of p-p65/p65 in tissues, which in turn regulated the PI3K/AKT/NF-κB signaling pathway. Conclusions. TSS, through regulating PI3K/AKT/NF-κB signaling axis, can alleviate depression-like behaviors and elevate neuroendocrine hormone levels and inflammatory factor levels. [ABSTRACT FROM AUTHOR]

Context Hypothalamic inflammation and dysfunction may be induced by high-fat diets. However, the mechanisms involved in this process have not been fully elucidated. Objective To evidence, in animal models, of how a high-fat diet influence the mechanisms involved in hypothalamic inflammation. Data sources Scopus, PubMed/Medline, Web of Science, Science Direct, and Embase databases were searched. Data extraction The exclusion criteria were human studies, studies with medicinal products or other substances not related to food, paper reviews, studies that used a surgical intervention or an intervention with food to reverse hypothalamic inflammation, and studies with genetically modified animals. The identified studies were evaluated according to the following inclusion criteria: animal studies, studies in which a control group was included in the experimental design, and studies in which markers of inflammation in the hypothalamus were evaluated. Data analysis A total of 322 studies were found, of which 9 met the inclusion criteria for a systematic review, conducted in accordance with the PRISMA guidelines, and were included in this review. Conclusion The exposure of rodents to high-fat diets promoted an increase in levels of several pro-inflammatory cytokines and other proteins involved in the inflammatory process in the hypothalamus. This process was associated with increased glial cell activity. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is the most prevalent degenerative joint disease. In vitro experiments are an intuitive method used to investigate its early pathogenesis. Chondrocyte inflammation models in rats and mice are often used as in vitro models of OA. However, similarities and differences between them in the early stages of inflammation have not been reported. Objective: This paper seeks to compare the chondrocyte phenotype of rats and mice in the early inflammatory state and identify chondrocytes suitable for the study of early OA. Methods: Under similar conditions, chondrocytes from rats and mice were stimulated using the same IL-1β concentration for a short period of time. The phenotypic changes of chondrocytes were observed under a microscope. The treated chondrocytes were subjected to RNA-seq to identify similarities and differences in gene expression. Chondrocytes were labelled with EdU for proliferation analysis. Cell proliferation-associated proteins, including minichromosome maintenance 2 (MCM2), minichromosome maintenance 5 (MCM5), Lamin B1, proliferating cell nuclear antigen (PCNA), and Cyclin D1, were analysed by immunocytochemical staining, cell immunofluorescence, and Western blots to verify the RNA-seq results. Results: RNA-seq revealed that the expression patterns of cytokines, chemokines, matrix metalloproteinases, and collagen were similar between the rat and mouse chondrocyte inflammation models. Nonetheless, the expression of proliferation-related genes showed the opposite pattern. The RNA-seq results were further verified by subsequent experiments. The expression levels of MCM2, MCM5, Lamin B1, PCNA, and Cyclin D1 were significantly upregulated in rat chondrocytes (P < 0.05) and mouse chondrocytes (P < 0.05). Conclusions: Based on the findings, the rat chondrocyte inflammation model may help in the study of the early pathological mechanism of OA. [ABSTRACT FROM AUTHOR]

Background. The flower of Abelmoschus manihot (AM) has been widely used in the treatment of chronic inflammatory diseases, including ulcerative colitis. This paper aimed to confirm the therapeutic effect of AM on ulcerative colitis (UC) and explore its mechanism. Methods. Mouse models were induced by 2.5% dextran sulfate sodium (DSS) and treated with AM. UC signs, symptoms, colon macroscopic lesion scores, and disease activity index (DAI) scores were observed. Colon levels of interleukin- (IL-) 6, IL-1β, IL-18, IL-17, tumor necrosis factor- (TNF-) α, and IL-10 were quantified by ELISA. The colon protein expression levels of NLRP3, ASC, caspase 1 p10, β-arrestin1, ZO-1, occludin-1, and claudin-1 were examined by immunohistochemistry and western blotting. The mRNA levels of IL-1β, IL-18, NLRP3, ASC, and caspase 1 p10 in the colon were determined by real-time quantitative polymerase chain reaction (qPCR). Results. After treatment with AM, the mortality of mice, pathological damage to the colon, splenomegaly, and the spleen coefficient were decreased. AM reduced the levels of proinflammatory cytokines (IL-6, IL-1β, IL-18, IL-17, and TNF-α) and increased the level of IL-10. The mRNA expression levels of NLRP3, ASC, and caspase 1 in colon tissue were decreased by AM in a dose-dependent manner. In addition, AM also reduced the protein expression of NLRP3, ASC, caspase 1 p10, IL-1β, IL-18, and β-arrestin1 in the colon tissue of model mice. Western blot analysis confirmed that AM increased the expression of occludin-1, claudin-1, and ZO-1 in a dose-dependent manner. Conclusion. This study shows that AM has a significant therapeutic effect on mice with UC, and the mechanism may be related to the inhibition of the β-arrestin1/NLRP3 inflammasome signaling pathway and the protection of intestinal barrier function. [ABSTRACT FROM AUTHOR]

Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research. [Display omitted] [ABSTRACT FROM AUTHOR]