Traditional Chinese medicine improves myasthenia gravis by regulating the symbiotic homeostasis of the intestinal microbiota and host

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies that is dependent on T-cell immunity and complement participation and mainly involves neuromuscular junctions. In this study, 30 patients with myasthenia gravis were selected and divided into pretreatment (Case group) and posttreatment (Treatment group) and 30 healthy volunteers (CON group) were included. Among them, the treatment group was treated with Modified Buzhong Yiqi Decoction (MBZYQD), and the levels of antibodies such as AChR, Musk and Titin in blood and intestinal microbiota were compared before treatment (Case group), after treatment (Treatment group) and in healthy volunteers (CON group). The results showed that after treatment with MBZYQD, the antibody levels of AChR, MuSK, and Titin and the inflammatory factor level of IL-6, IL-1β, and IL-22 in MG patients decreased significantly and nearly returned to a healthy level. In addition, after treatment with MBZYQD, the diversity, structure and function of intestinal microorganisms in MG patients also recovered to a healthy level. At the phylum level, the relative abundance of Proteobacteria in the Case group increased significantly, accompanied by a significant decrease in the relative abundance of Bacteroides compared with that in the CON group, the relative abundance of Proteobacteria and Bacteroides in the Treatment group was similar to that in the CON group. At the genus level, the relative abundance of Shigella in the Case group was significantly increased, accompanied by a significant decrease in the relative abundance of Prevotella, and the relative abundance of Shigella and Prevotella in Treatment group was similar to that in the CON group. Moreover, the fluorobenzoate degradation pathway (KO00364) was significantly increased in the Case group, while this pathway was significantly decreased in the Treatment group. In conclusion, MBZYQD can improve the immune function of the host by regulating the diversity, structure and function of the intestinal microbiota to treat myasthenia gravis

Zwitterion-functionalized dendrimer-entrapped gold nanoparticles for serum-enhanced gene delivery to inhibit cancer cell metastasis

We demonstrate a novel serum-enhanced gene delivery approach using zwitterion-functionalized dendrimer-entrapped gold nanoparticles (Au DENPs) as a non-viral vector for inhibition of cancer cell metastasis in vitro. Poly(amidoamine) dendrimers of generation 5 decorated with zwitterion carboxybe taine acrylamide (CBAA) and lysosome-targeting agent morpholine (Mor) were utilized to entrap gold NPs. We show that both Mor-modified and Mor-free Au DENPs are cytocompatible and can effectively deliver plasmid DNA encoding different reporter genes to cancer cells in medium with or without serum. Strikingly, due to the antifouling property exerted by the attached zwitterion CBAA, the gene delivery efficiency of Mor-modified Au DENPs and the Mor-free Au DENPs in the serum-containing medium are 1.4 and 1.7 times higher than the corresponding vector in serum-free medium, respectively. In addition, the Mor-free vector has a better gene expression efficiency than the Mor-modified one although the Mor modification enables the polyplexes to have enhanced cancer cell uptake. Wound healing and hyperme thylated in cancer 1 (HIC1) protein expression assay data reveal that the expression of HIC1 gene in cancer cells enables effective inhibition of cell migration. Our findings suggest that the created zwitterion-functionalized Au DENPs may be employed as a powerful vector for serum-enhanced gene therapy of different diseases.info:eu-repo/semantics/publishedVersio

A study on the correlation between hemoglobin concentration and the storage quality of suspended red blood cells prepared from the whole blood of Tibetan male residents

BackgroundPrevious studies reported that the blood of Tibetans living at different altitudes may vary slightly. There is evidence that the harsh environmental conditions at high altitudes, such as low pressure and hypoxia, may affect the morphology and hemorheology of red blood cells (RBCs). Hypoxia would increase the levels of hemoglobin ([Hb]) and hematocrit (Hct), potentially increasing blood hyperviscosity and compromising blood collection and transfusions. Therefore, it is critical to investigate the in vitro storage quality of Tibetan RBCs.ObjectivesIn this study, the in vitro quality of suspended RBCs (SRBCs) prepared from whole blood (WB) of Tibetan residents with varying Hb concentrations ([Hb]) was measured during storage, and the relationship between the major factors in RBC storage and [Hb] was studied.Materials and methodsThe WB of Tibetan men was divided into three groups based on [Hb] levels (group A: 120 < Hb ≤ 185 g/L; group B: 185 < Hb ≤ 210 g/L; group C: Hb > 210 g/L). The SRBCs prepared from WB were examined aseptically on days 1, 14, 21, and 35 after storage.Results[Hb] was not correlated with mean corpuscular volume (MCV), adenosine triphosphate (ATP), pH, P50, and hemolysis. There was a moderate or strong negative association between platelets (PLT) and [Hb] from days 1 to 35, and the PLT number of group C was lower than group A during storage. Group C had the highest change rates of electrolytes, glucose, and lactate, and there were moderate or strong positive correlations between lactate and [Hb] (r = 0.3772, p = 0.0045), glucose and [Hb] (r = 0.5845, p < 0.0001), Na+ and [Hb] (r = 0.3966, p = 0.0027), and K+ and [Hb] (r = 0.4885, p = 0.0002). Group B had the highest change rates of 2,3-DPG on day 35, and there was a negative correlation between 2,3-DPG and [Hb] (r = −0.4933, p = 0.0001).ConclusionsThese new data on the [Hb] could have implications for researchers wishing to study the storage quality of Tibetan SRBCs, particularly in the context of erythrocyte metabolism, and we propose finding a new, suitable alternative solution for plateau SRBCs, particularly the blood with [Hb] greater than 185 g/L. Our results could have important implications for researchers wishing to study the potential framework of high-altitude-induced SRBC storage lesions

Prognosis of immune checkpoint inhibitor-induced myasthenia gravis: a single center experience and systematic review

BackgroundImmune checkpoint inhibitors (ICI)-induced myasthenia gravis (MG) is an uncommon but potentially fatal neurotoxicity. We aim to help physicians familiarize themselves with the clinical characteristics of ICI-induced MG, facilitating early diagnosis and prompt intervention.MethodsWe searched the Chinese People’s Liberation Army General Hospital medical record system from January 2017 to August 2023 for patients diagnosed with ICI-induced MG. We systematically reviewed the literature until August 2023 to identify all similar patients. We collected clinical information on these patients.Results110 patients were identified, 9 from our institution and 101 from case reports. In our institution, Median age was 66 years (range: 49–79 years). 6 were males. The most common was lung cancer (n = 4). All patients had no previous history of MG and received PD-1 or PD-L1 inhibitors. The median time from ICI initiation to first MG symptoms was 4 weeks (range: 2–15 weeks). ICIs were discontinued in all patients. Most patients initially received high-dose corticosteroids, and their symptoms improved. Some patients are discharged with corticosteroids maintenance therapy. In addition, 55 patients (50%) with concomitant myositis and/or myocarditis and MG-induced mortality were more common in the myositis and/or myocarditis group (10.9% vs. 34.5%, p = 0.016). Overlap of myositis with MG (OR = 3.148, p = 0.009) and anti-AChR antibody positivity (OR = 3.364, p = 0.005) were both significantly associated with poor outcomes.ConclusionOur study reveals the prognosis of ICI-induced MG and suggests that myositis and/or myocarditis are severe comorbidities of ICI-induced MG, emphasizing the importance of early diagnosis and clinical intervention

Comparative efficacy of six programmed cell death Protein-1 inhibitors as first-line treatment for advanced non-small cell lung cancer: a multicenter retrospective cohort study

The purpose of this study was to assess the comparative efficacy of six programmed cell death-1 inhibitors (nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab) that have been used as first-line therapy for Chinese patients with advanced non-small cell lung cancer (NSCLC), which remains unclear. We determined the differences in efficacy by observing patient survival data, with the goal of informing future treatment options. Retrospective data analysis from June 2015 to April 2023 included 913 patients across six groups: nivolumab (123%, 13.5%), pembrolizumab (421%, 46.1%), sintilimab (239%, 26.1%), tislelizumab (64%, 7.0%), toripalimab (39%, 4.3%), and camrelizumab (27%, 3.0%). The median progression-free survival (PFS) for each group was 16.0, 16.1, 18.4, 16.9, 23.7, and 12.8 months, and the median overall survival (OS) was 33.7, 36.1, 32.5, not reached, 30.9 and 46.0 months for the nivolumab, sintilimab, pembrolizumab, tislelizumab, toripalimab, and camrelizumab groups, respectively. While differences existed in the objective response rates among groups (p < 0.05), there were no significant differences (all p > 0.05) in PFS or OS. The findings suggest comparable efficacy among these PD-1 inhibitors for NSCLC treatment, underscoring their collective suitability and aiding treatment decisions

Inhibition of neutrophil extracellular trap formation attenuates NLRP1-dependent neuronal pyroptosis via STING/IRE1α pathway after traumatic brain injury in mice

IntroductionIncreased neutrophil extracellular trap (NET) formation has been reported to be associated with cerebrovascular dysfunction and neurological deficits in traumatic brain injury (TBI). However, the biological function and underlying mechanisms of NETs in TBI-induced neuronal cell death are not yet fully understood.MethodsFirst, brain tissue and peripheral blood samples of TBI patients were collected, and NETs infiltration in TBI patients was detected by immunofluorescence staining and Western blot. Then, a controlled cortical impact device was used to model brain trauma in mice, and Anti-Ly6G, DNase, and CL-amidine were given to reduce the formation of neutrophilic or NETs in TBI mice to evaluate neuronal death and neurological function. Finally, the pathway changes of neuronal pyroptosis induced by NETs after TBI were investigated by administration of peptidylarginine deiminase 4 (a key enzyme of NET formation) adenovirus and inositol-requiring enzyme-1 alpha (IRE1α) inhibitors in TBI mice.ResultsWe detected that both peripheral circulating biomarkers of NETs and local NETs infiltration in the brain tissue were significantly increased and had positive correlations with worse intracranial pressure (ICP) and neurological dysfunction in TBI patients. Furthermore, the depletion of neutrophils effectively reduced the formation of NET in mice subjected to TBI. we found that degradation of NETs or inhibition of NET formation significantly inhibited nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 1 (NLRP1) inflammasome-mediated neuronal pyroptosis after TBI, whereas these inhibitory effects were abolished by cyclic GMP-AMP (cGAMP), an activator of stimulating Interferon genes (STING). Moreover, overexpression of PAD4 in the cortex by adenoviruses could aggravate NLRP1-mediated neuronal pyroptosis and neurological deficits after TBI, whereas these pro-pyroptotic effects were rescued in mice also receiving STING antagonists. Finally, IRE1α activation was significantly upregulated after TBI, and NET formation or STING activation was found to promote this process. Notably, IRE1α inhibitor administration significantly abrogated NETs-induced NLRP1 inflammasome-mediated neuronal pyroptosis in TBI mice.DiscussionOur findings indicated that NETs could contribute to TBI-induced neurological deficits and neuronal death by promoting NLRP1-mediated neuronal pyroptosis. Suppression of the STING/ IRE1α signaling pathway can ameliorate NETs-induced neuronal pyroptotic death after TBI

High-throughput Sequencing Analysis of Diversity and Spatial Heterogeneity of Fungal Community in Pit Muds of Different Ages for Baijiu Production

The fungal community structure, the relationship between fungal flora and physicochemical factors, and the prediction of fungal function in pit muds from different spatial positions of 10- and 50-year-old cellars at Jinhui liquor Co. Ltd. were studied by using Illumina NovaSeq high-throughput sequencing, redundancy analysis and Fungi Functional Guild (FUNGuild). The results showed that the fungal diversity and richness of the 10-year-old pit mud decreased with increasing depth; the fungal diversity of the 50-year-old pit mud showed an overall increasing trend, while the fungal richness initially decrease and then increased. Moreover, for the 10-year-old pit, the fungal diversity and richness of the upper layer of the pit wall were significantly higher than those of the other positions (P < 0.05), while for the 50-year-old cellar, the fungal diversity and richness of the bottom layer were significantly higher than those of the other locations (P < 0.05). The fungal diversity and richness were significantly higher in the wall of the 10-year-old cellar than the 50-year-old cellar (P < 0.05), but were significantly higher in the bottom of the 50-year-old cellar than the 10-year-old cellar (P < 0.05). A total of 21 fungal phyla and 520 genera were detected in all pit mud samples, the relative abundance of four dominant phyla (Ascomycota, Basidiomycota, Mortierellomycota and Rozellomycota) and most dominant genera such as Aspergillus and Kazachstania showed significant changes among pit ages and spatial locations (P < 0.05). Fusarium, Aspergillus, Saccharomyces and Monascus were positively correlated with the contents of water, humus, K+ and Ca2+, while Cladosporium and Vishniacozyma were positively correlated with pH. Seven nutritional modes of fungi were observed, mainly including saprophytic and pathological-saprophytic-symbiotic nutritional modes, and four single and seven mixed functional groups were determined. This study provides a theoretical basis for clarifying the structure and spatial distribution of fungal community in Jinhui Baijiu pit mud

Cardiovascular mortality by cancer risk stratification in patients with localized prostate cancer: a SEER-based study

PurposeThe risk of cardiovascular disease (CVD) mortality in patients with localized prostate cancer (PCa) by risk stratification remains unclear. The aim of this study was to determine the risk of CVD death in patients with localized PCa by risk stratification.Patients and methodsPopulation-based study of 340,806 cases in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with localized PCa between 2004 and 2016. The proportion of deaths identifies the primary cause of death, the competing risk model identifies the interaction between CVD and PCa, and the standardized mortality rate (SMR) quantifies the risk of CVD death in patients with PCa.ResultsCVD-related death was the leading cause of death in patients with localized PCa, and cumulative CVD-related death also surpassed PCa almost as soon as PCa was diagnosed in the low- and intermediate-risk groups. However, in the high-risk group, CVD surpassed PCa approximately 90 months later. Patients with localized PCa have a higher risk of CVD-related death compared to the general population and the risk increases steadily with survival (SMR = 4.8, 95% CI 4.6–5.1 to SMR = 13.6, 95% CI 12.8–14.5).ConclusionsCVD-related death is a major competing risk in patients with localized PCa, and cumulative CVD mortality increases steadily with survival time and exceeds PCa in all three stratifications (low, intermediate, and high risk). Patients with localized PCa have a higher CVD-related death than the general population. Management of patients with localized PCa requires attention to both the primary cancer and CVD

Strigolactone alleviates the salinity-alkalinity stress of Malus hupehensis seedlings

Salinity-alkalinity stress can remarkably affect the growth and yield of apple. Strigolactone (SL) is a class of carotenoid-derived compounds that functions in stress tolerance. However, the effects and mechanism of exogenous SL on the salinity-alkalinity tolerance of apple seedlings remain unclear. Here, we assessed the effect of SL on the salinity-alkalinity stress response of Malus hupehensis seedlings. Results showed that treatment with 100 μM exogenous SL analog (GR24) could effectively alleviate salinity-alkalinity stress with higher chlorophyll content and photosynthetic rate than the apple seedlings without GR24 treatment. The mechanism was also explored: First, exogenous GR24 regulated the expression of Na+/K+ transporter genes and decreased the ratio of Na+/K+ in the cytoplasm to maintain ion homeostasis. Second, exogenous GR24 increased the enzyme activities of superoxide, peroxidase and catalase, thereby eliminating reactive oxygen species production. Third, exogenous GR24 alleviated the high pH stress by regulating the expression of H+-ATPase genes and inducing the production of organic acid. Last, exogenous GR24 application increased endogenous acetic acid, abscisic acid, zeatin riboside, and GA3 contents for co-responding to salinity-alkalinity stress indirectly. This study will provide important theoretical basis for analyzing the mechanism of exogenous GR24 in improving salinity-alkalinity tolerance of apple