Search

Abstract Multiple sclerosis (MS) is an autoimmune disorder caused by chronic inflammatory reactions in the central nervous system. Currently, little is known about the changes of plasma proteomic profiles in Chinese patients with MS (CpwMS) and its relationship with the altered profiles of multi-omics such as metabolomics and gut microbiome, as well as potential molecular networks that underlie the etiology of MS. To uncover the characteristics of proteomics landscape and potential multi-omics interaction networks in CpwMS, Plasma samples were collected from 22 CpwMS and 22 healthy controls (HCs) and analyzed using a Tandem Mass Tag (TMT)-based quantitative proteomics approach. Our results showed that the plasma proteomics pattern was significantly different in CpwMS compared to HCs. A total of 90 differentially expressed proteins (DEPs), such as LAMP1 and FCG2A, were identified in CpwMS plasma comparing to HCs. Furthermore, we also observed extensive and significant correlations between the altered proteomic profiles and the changes of metabolome, gut microbiome, as well as altered immunoinflammatory responses in MS-affected patients. For instance, the level of LAMP1 and ERN1 were significantly and positively correlated with the concentrations of metabolite L-glutamic acid and pro-inflammatory factor IL-17 (Padj

Multiple sclerosis (MS) is an autoimmune disorder caused by chronic inflammatory reactions in the central nervous system. Currently, little is known about the changes of plasma proteomic profiles in Chinese patients with MS (CpwMS) and its relationship with the altered profiles of multi-omics such as metabolomics and gut microbiome, as well as potential molecular networks that underlie the etiology of MS. To uncover the characteristics of proteomics landscape and potential multi-omics interaction networks in CpwMS, Plasma samples were collected from 22 CpwMS and 22 healthy controls (HCs) and analyzed using a Tandem Mass Tag (TMT)-based quantitative proteomics approach. Our results showed that the plasma proteomics pattern was significantly different in CpwMS compared to HCs. A total of 90 differentially expressed proteins (DEPs), such as LAMP1 and FCG2A, were identified in CpwMS plasma comparing to HCs. Furthermore, we also observed extensive and significant correlations between the altered proteomic profiles and the changes of metabolome, gut microbiome, as well as altered immunoinflammatory responses in MS-affected patients. For instance, the level of LAMP1 and ERN1 were significantly and positively correlated with the concentrations of metabolite L-glutamic acid and pro-inflammatory factor IL-17 (Padj < 0.05). However, they were negatively correlated with the amounts of other metabolites such as L-tyrosine and sphingosine 1-phosphate, as well as the concentrations of IL-8 and MIP-1α. This study outlined the underlying multi-omics integrated mechanisms that might regulate peripheral immunoinflammatory responses and MS progression. These findings are potentially helpful for developing new assisting diagnostic biomarker and therapeutic strategies for MS. [ABSTRACT FROM AUTHOR]

Background: Diffuse brain injury (DBI) models are characterized by intense global brain inflammation and edema, which characterize the most severe form of TBI. In a previous experiment, we found that fingolimod promoted recovery after controlled cortical impact injury (CCI) by modulating inflammation around brain lesions. However, it remains unclear whether fingolimod can also attenuate DBI because of its different injury mechanisms. Furthermore, whether fingolimod has additional underlying effects on repairing DBI is unknown. Methods: The impact acceleration model of DBI was established in adult Sprague–Dawley rats. Fingolimod (0.5 mg/kg) was administered 0.5, 24, and 48 h after injury for 3 consecutive days. Immunohistochemistry, immunofluorescence analysis, cytokine array, and western blotting were used to evaluate inflammatory cells, inflammatory factors, AQP4 polarization, apoptosis in brain cells, and the accumulation of APP after DBI in rats. To evaluate the function of the glymphatic system (GS), a fluorescent tracer was injected into the cistern. The neural function of rats with DBI was evaluated using various tests, including the modified neurological severity score (mNSS), horizontal ladder‐crossing test, beam walking test, and tape sensing and removal test. Brain water content was also measured. Results: Fingolimod administration for 3 consecutive days could reduce the levels of inflammatory cytokines, neutrophil recruitment, microglia, and astrocyte activation in the brain following DBI. Moreover, fingolimod reduced apoptotic protein expression, brain cell apoptosis, brain edema, and APP accumulation. Additionally, fingolimod inhibited the loss of AQP4 polarization, improved lymphatic system function, and reduced damage to nervous system function. Notably, inhibiting the GS weakened the therapeutic effect of fingolimod on the neurological function of rats with DBI and increased the accumulation of APP in the brain. Conclusions: In brief, these findings suggest that fingolimod alleviates whole‐brain inflammation and GS system damage after DBI and that inhibiting the GS could weaken the positive effect of fingolimod on nerve function in rats with DBI. Thus, inhibiting inflammation and regulating the GS may be critical for the therapeutic effect of fingolimod on DBI. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To observe the neuroregulatory effects of Chaihu Shugan powder and Banxia Houpo decoction combined with Wuxing acupuncture on anxiety and depression after stroke and its effects on immune inflammatory response, cognitive function impairment, hypothalamic-pituitary-gonadal axis (HPG) and hypothalamicpituitary-thyroid axis (HPT). METHODS: A total of 102 patients with post-stroke anxiety and depression admitted into the hospital from Mar. 2021 to May 2023 were extracted to be divided into 51 cases in the Wuxing acupuncture group (2 cases were shed and 49 cases were eventually included), and 51 cases in the prescription combination group (2 cases were shed and 49 cases were eventually included) according to the random number table method. Both groups were given conventional Western medicine basic treatment, the Wuxing acupuncture group received Wuxing acupuncture treatment based on the conventional Western medicine basic treatment, and the prescription combination group was treated with Chaihu Shugan powder and Banxia Houpo decoction on the basis of the Wuxing acupuncture group. Clinical efficacy of two groups was compared. Traditional Chinese medicine syndrome score, Mini-Mental State Examination ( MMSE) score, Generalized Anxiety Disorder Scale ( GAD-7) score, Hamilton Depression Scale (HAMD) score and Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF) score of two groups before and after treatment were compared. Serum levels of nerve growth factor ( NGF), interleukin-1β (IL-1β), glial fibrillary acidic protein (GFAP), interleukin-17A (IL-17a), thyroid stimulating hormone (TSH), 5-hydroxytryptamine (5-HT) and estradiol 2 (E2) were measured before and after treatment. RESULTS: The total effective rate of the prescription combination group was 97. 96% (48/49), higher than 81. 63% (40/49) of the Wuxing acupuncture group, the difference was statistically significant (P < 0. 05). After treatment, the scores of anxiety and depression, epigastric fullness, chest and hypochondriac distension, frequent sighing in the prescription combination group were lower than those in the Wuxing acupuncture group, the scores of HAMD and GAD-7 were lower than those in Wuxing acupuncture group, and the scores of MMSE and Q-LES-Q-SF were higher than those in Wuxing acupuncture group, with statistically significant differences (P<0. 05). After treatment, levels of of IL-1β, IL-17a and GFAP in prescription combination group were lower than those in Wuxing acupuncture group, and levels of NGF in prescription combination group were significantly higher than those in Wuxing acupuncture group, levels of 5-HT, E2 and TSH in prescription combination group were higher than those in Wuxing acupuncture group, with statistically significant differences (P<0. 05). CONCLUSIONS: Chaihu Shugan powder and Banxia Houpo decoction combined with Wuxing acupuncture in the treatment of patients with post-stroke anxiety and depression can reduce the immune inflammatory response and neurological and cognitive function damage, regulate HPG and HPT, improve anxiety and depression, relieve the disease, improve quality of life and clinical efficacy. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate and analyze the clinical application value of thoracoscopic segmentectomy and lobectomy in patients with invasive pulmonary adenocarcinoma. Methods: 286 patients with invasive pulmonary adenocarcinoma who underwent segmentectomy or lobectomy at the First Hospital of Jiaxing City from January 2018 to June 2020 were retrospectively analyzed. Patients were divided into a thoracoscopic segmentectomy group(n=97) and a lobectomy group (n=189). Patients were compared after obtaining 1:1 propensity scorematched cohorts. Outcome indicators included surgery-related indicators, immune-inflammation-related indicators, postoperative complications, recurrence, and metastasis. Results: After 1:1 propensity score matching, 93 patients were included in each group. We found that the volume of intraoperative blood loss in the segmentectomy group was significantly less than in the lobectomy group (P=0.014). The duration of postoperative drainage (P = 0.005) and hospitalization (P=0.002) in the segmentectomy group were significantly shorter than in the lobectomy group. In terms of immunoinflammatory response, compared with the lobectomy group, white blood cells, neutrophils, SII, and NLR in the segmentectomy group were significantly lower than in the lobectomy group (P< 0.05). The recurrence-free survival (RFS) rates in the segmentectomy and lobectomy were 80.5% and 88.2% at 1 year and 35.1% and 52.6% at 3 years, respectively, and the difference was statistically significant (P<0.05). The segmentectomy group achieved similar outcomes to the lobectomy group at 1 year and 3 years (P > 0.05). Multivariate COX regression analysis showed that CAR was an independent risk factor for RFS in patients undergoing invasive adenocarcinoma surgery. Conclusion: Compared with lobectomy, thoracoscopic segmentectomy can effectively reduce the postoperative inflammatory response in patients with early invasive lung adenocarcinoma and promote patient recovery. Although segmentectomy is associated with a higher recurrence rate in the short term for patients with early invasive lung adenocarcinoma, the associated survival rate is similar to the lobectomy group. Segmentectomy should be considered in the treatment of early invasive lung adenocarcinoma. Meanwhile, postoperative CAR represents an independent risk factor for early postoperative recurrence in patients with IAC. [ABSTRACT FROM AUTHOR]

The severity of SARS-CoV2 infection, Covid19 disease, should account for the diversity of human individual immunoinflammatory responses. Serum immunological markers during Covid19 illness may lead to individualized therapeutics with better outcomes. Efficient treatment for Covid19 may require: 1) early disease detection, 2) combined drug therapy for 3) targeting the virus replication cycle, and 4) individualized drug treatment for specific immunoinflammatory human profile responses administered in a 5) timely manner. Covid19 is unlikely to be the last emergent human disease with fast pandemic potential. Gathering knowledge on the individual human host profiles of immunoinflammatory responses is an opportunity that could lead us to understand individual differences in response to infection at the individual and population level, paving the way to faster, more efficient strategies to tackle upcoming infectious diseases. This is a position paper based on an integrative non-exhaustive literature revision.

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD), especially advanced metabolic dysfunction-associated steatohepatitis (MASH), have an increased risk of cardiovascular diseases (CVDs). Whether CVD events will, in turn, influence the pathogenesis of MASLD remains unknown. Here, we show that myocardial infarction (MI) accelerates hepatic pathological progression of MASLD. Patients with MASLD who experience CVD events after their diagnosis exhibit accelerated liver fibrosis progression. MI promotes hepatic fibrosis in mice with MASH, accompanied by elevated circulating Ly6Chi monocytes and their recruitment to damaged liver tissues. These adverse effects are significantly abrogated when deleting these cells. Meanwhile, MI substantially increases circulating and cardiac periostin levels, which act on hepatocytes and stellate cells to promote hepatic lipid accumulation and fibrosis, finally exacerbating hepatic pathological progression of MASH. These preclinical and clinical results demonstrate that MI alters systemic homeostasis and upregulates pro-fibrotic factor production, triggering cross-disease communication that accelerates hepatic pathological progression of MASLD. [Display omitted] • CVD accelerates liver fibrosis in patients with MASLD • MI exacerbates liver damage in multiple MASH models • Ly6Chi monocytes partially mediate the MI-induced liver damage • Periostin promotes hepatic steatosis and fibrosis in mice with MASH Xie et al. show that myocardial infarction (MI) accelerates the hepatic pathological progression of MASLD by promoting the production of CCR2+Ly6Chi monocytes, triggering hepatic immunoinflammatory response, and upregulating cardiac periostin contents, which in turn acts on hepatocytes and stellate cells to promote hepatic lipid accumulation and fibrosis. [ABSTRACT FROM AUTHOR]

Colonization of Helicobacter pylori ( H. pylori ) induces immune and inflammatory response in gastric mucosa. Trimethylamine N -oxide (TMAO), from diet and metabolite through the action of gut microbiota, has been linked to inflammatory diseases. To investigate the effects of TMAO and H. pylori infection on gene expression in gastric epithelial cells, Human gene chip Affymetrix HTA 2.0 was used in this study. 1312 genes were identified as differentially expressed genes in GES-1 cells with H. pylori and TMAO co-treatment compared to the control. GO and KEGG analyses indicated that the functions of these differentially expressed genes were related closely with immune inflammation. GO-network showed that Toll-like receptor signaling pathway was the most important biological processes and 49 up-regulated genes related to immune inflammation were obtained. The synergistic effects of H. pylori and TMAO enhanced the genes expression of IL-6, CXCL1, CXCL2, FOS and C3 related to immune inflammation in comparison with those of non-infected control cells, H. pylori -infected cells, and TMAO-stimulated cells. RT-PCR verified the expression levels of IL-6, CXCL1. Additionally, expression levels of 2053 genes were altered and 52 immunoinflammatory genes were upregulated in comparison with H. pylori -infected cells. This study suggested that TMAO altered the expression levels of immunoinflammatory genes induced by H. pylori infection, and the synergistic effects of H. pylori and TMAO provided novel insights into the development of chronic gastritis, gastric ulcer and gastric cancer. [ABSTRACT FROM AUTHOR]