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Sepsis-induced myocardial dysfunction (SIMD) is a severe complication in sepsis, manifested as myocardial systolic dysfunction, which is associated with poor prognosis and higher mortality. Mitophagy, a self-protective mechanism maintaining cellular homeostasis, plays an indispensable role in cardioprotection. This study aimed to unveil the cardioprotective effects of Baricitinib on LPS-induced myocardial dysfunction and its effect on mitophagy. Herein, we demonstrated that LPS induced severe myocardial dysfunction and initiated mitophagy in septic mice hearts. Despite the initiation of mitophagy, a significant number of apoptotic cells and damaged mitochondria persisted in the myocardium, and myocardial energy metabolism remained impaired, indicating that the limited mitophagy was insufficient to mitigate LPS-induced damage. The JAK2-AKT-mTOR signaling pathway is activated in LPS-induced cardiomyocytes and in the hearts of septic mice. Baricitinib administration remarkably improved cardiac function, suppressed systemic inflammatory response, attenuated histopathological changes, inhibited cardiac cell apoptosis and alleviated myocardial damage in septic mice. Furthermore, Baricitinib treatment significantly enhanced PINK1-Parkin-mediated mitophagy, increased autophagosomes, decreased impaired mitochondria, and restored myocardial energy metabolism. Mechanically, the limited mitophagy in septic myocardium was associated with increased p-ULK1 (Ser757), which was regulated by p-mTOR. Baricitinib reduced p-ULK1 (Ser757) and enhanced mitophagy by inhibiting the JAK2-AKT-mTOR signaling pathway. Inhibition of mitophagy with Mdivi-1 reversed the cardiac protective and anti-inflammatory effects of Baricitinib in septic mice. These findings suggest that Baricitinib attenuates SIMD by enhancing mitophagy in cardiomyocytes via the JAK2-AKT-mTOR signaling pathway, providing a novel mechanistic and therapeutic insight into the SIMD.
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RBM45 is an RNA-binding protein with roles in neural development by regulating RNA splicing. Its dysfunction and aggregation are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). RBM45 harbors three RRM domains that potentially bind RNA. While the recognitions of RNA by its N-terminal tandem RRM domains (RRM1 and RRM2) have been well understood, the RNA-binding property of its C-terminal RRM (RRM3) remains unclear. In this work, we identified that the RRM3 of RBM45 sequence-specifically binds RNA with a GACG sequence, similar but not identical to those recognized by the RRM1 and RRM2. Further, we determined the crystal structure of RBM45RRM3 in complex with a GACG sequence-containing single-stranded DNA. Our structural results, together with the RNA-binding assays of mutants at key amino acid residues, revealed the molecular mechanism by which RBM45RRM3 recognizes an RNA sequence. Our finding on the RNA-binding property of the individual RRM module of RBM45 provides the foundation for unraveling the RNA-binding characteristics of full-length RBM45 and for understanding the biological functions of RBM45.
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Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by diverse clinical manifestations and organ damage. Despite its elusive etiology, dysregulated subsets and functions of B cells are pivotal in SLE pathogenesis. Peoniflorin-6'-O-benzene sulfonate (CP-25), an esterification modification of Paeoniflorin, exhibits potent anti-inflammatory and immunomodulatory properties in autoimmune diseases (AID). However, the involvement of CP-25 and its target, GRK2, in SLE development has not been explored. In this study, we demonstrate that both genetic deficiency and pharmacological inhibition of GRK2 attenuate autoantibodies production, reduce systemic inflammation, and mitigate histopathological alterations in the spleen and kidney in the pristane-induced mouse SLE model. Importantly, our findings highlight that both genetic deficiency and pharmacological inhibition of GRK2 suppress plasma cells generation and restore dysregulated B-cell subsets by modulating two crucial transcription factors, Blimp1 and IRF4. Collectively, targeting GRK2 with CP-25 emerges as a promising therapeutic approach for SLE.
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Modelos Animais de Doenças , Quinase 2 de Receptor Acoplado a Proteína G , Lúpus Eritematoso Sistêmico , Plasmócitos , Animais , Feminino , Camundongos , Anti-Inflamatórios/farmacologia , Autoanticorpos/sangue , Diferenciação Celular/efeitos dos fármacos , Quinase 2 de Receptor Acoplado a Proteína G/antagonistas & inibidores , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Glucosídeos/farmacologia , Rim/patologia , Rim/efeitos dos fármacos , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monoterpenos/farmacologia , Plasmócitos/efeitos dos fármacos , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Baço/efeitos dos fármacos , Baço/patologia , Baço/imunologia , TerpenosRESUMO
P2Y14 receptor (P2Y14R) is activated by uridine 5'-diphosphate-glucose, which is involved in many human inflammatory diseases. Based on the molecular docking analysis of currently reported P2Y14R antagonists and the crystallographic overlap study between the reported P2Y14R antagonist compounds 6 and 9, a series of N-substituted-acetamide derivatives were designed, synthesized, and identified as novel and potent P2Y14R antagonists. The most potent antagonist, compound I-17 (N-(1H-benzo[d]imidazol-6-yl)-2-(4-bromophenoxy)acetamide, IC50 = 0.6 nM) without zwitterionic character, showed strong binding ability to P2Y14R, high selectivity, moderate oral bioactivity, and improved pharmacokinetic profiles. In vitro and in vivo evaluation demonstrated that compound I-17 had satisfactory inhibitory activity on the inflammatory response of monosodium urate (MSU)-induced acute gouty arthritis. I-17 decreased inflammatory factor release and cell pyroptosis through the NOD-like receptor family pyrin domain-containing 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway. Thus, compound I-17, with potent P2Y14R antagonistic activity, in vitro and in vivo efficacy, and favorable bioavailability (F = 75%), could be a promising lead compound for acute gouty arthritis.
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Acetamidas , Simulação de Acoplamento Molecular , Receptores Purinérgicos P2 , Acetamidas/farmacologia , Acetamidas/química , Acetamidas/síntese química , Acetamidas/farmacocinética , Humanos , Animais , Receptores Purinérgicos P2/metabolismo , Camundongos , Masculino , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/metabolismo , Relação Estrutura-Atividade , Antagonistas do Receptor Purinérgico P2/farmacologia , Antagonistas do Receptor Purinérgico P2/química , Antagonistas do Receptor Purinérgico P2/síntese química , Descoberta de Drogas , Ratos , Cristalografia por Raios X , Ratos Sprague-Dawley , Estrutura MolecularRESUMO
Sludge is an inevitable by-product of the sewage treatment process and its high moisture content poses significant challenges for its treatment and disposal. This study focuses on the technology of sludge deep dewatering using liquefied dimethyl ether (DME) and explores the relationship between operating parameters (DME/sludge ratio, extraction time and stirring speed) and the water content of the sludge after deep dewatering. After deep dewatering, the sludge's lower heating value (LHV) was significantly increased. The dehydrated filtrate is highly biodegradable and could be treated together with sewage. Based on the response surface method of central composite design, a second-order regression model of the above three variables and sludge water content as the response was established. Finally, the operating conditions diagram was drawn by target water content (36.96 wt.%) which meets the requirement of self-sustained incineration and model equation. This study provides a valuable perspective on sludge drying and fuelisation.
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Mouse androgenetic haploid embryonic stem cells (mAG-haESCs) can be utilized to uncover gene functions, especially those of genes with recessive effects, and to produce semicloned mice when injected into mature oocytes. However, mouse haploid cells undergo rapid diploidization during long-term culture in vitro and subsequently lose the advantages of haploidy, and the factors that drive diploidization are poorly understood. In this study, we compared the small RNAs (sRNAs) of mAG-haESCs, normal embryonic stem cells (ESCs), and mouse round spermatids by high-throughput sequencing and identified distinct sRNA profiles. Several let-7 family members and miR-290-295 cluster microRNAs (miRNAs) were found significantly differentially transcribed. Knockdown and overexpression experiments showed that let-7a and let-7g suppress diploidization while miR-290a facilitates diploidization. Our study revealed the unique sRNA profile of mAG-haESCs and demonstrated that let-7a overexpression can mitigate diploidization in mAG-haESCs. These findings will help us to better understand mAG-haESCs and utilize them as tools in the future.
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Akkermansia muciniphila is a mucin-degrading probiotic that colonizes the gastrointestinal tract. Genomic analysis identified a set of genes involved in the biosynthesis of corrin ring, including the cobalt factor II methyltransferase CbiL, in some phylogroups of A. muciniphila, implying a potential capacity for de novo synthesis of cobalamin. In this work, we determined the crystal structure of CbiL from A. muciniphila at 2.3 Å resolution. AmCbiL exists as a dimer both in solution and in crystal, and each protomer consists of two α/ß domains, the N-terminal domain and the C-terminal domain, consistent with the folding of typical class III MTases. The two domains create an open trough, potentially available to bind the substrates SAM and cobalt factor II. Sequence and structural comparisons with other CbiLs, assisted by computer modeling, suggest that AmCbiL should have cobalt factor II C-20 methyltransferase activity. Our results support that certain strains of A. muciniphila may be capable of synthesizing cobalamin de novo.
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Akkermansia , Metiltransferases , Modelos Moleculares , Metiltransferases/química , Metiltransferases/metabolismo , Metiltransferases/genética , Akkermansia/enzimologia , Cristalografia por Raios X , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Vitamina B 12/metabolismo , Vitamina B 12/química , Conformação ProteicaRESUMO
BACKGROUND: Hypertension, a prevalent disease, is a significant risk factor for coronary heart disease. Huoxue Qianyang Qutan Recipe (HQQR), a traditional Chinese herbal remedy, has been used for treating hypertension over several years. OBJECTIVE: This study assesses HQQR's efficacy for controlling blood pressure among patients with hypertension related to blood stasis, yang hyperactivity and phlegm. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, from July 2020 to June 2022. Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography. Participants aged 18-80 years, exhibiting traditional Chinese medicine syndromes of blood stasis, yang hyperactivity or phlegm, along with grades 1 or 2 hypertension, were randomly categorized into two groups. The intervention group was given HQQR granules alongside conventional hypertension treatment, while the control group was given placebo granules in addition to conventional treatment for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was clinic blood pressure, whereas secondary outcomes included metabolic indices (e.g., homeostasis model assessment of insulin resistance [HOMA-IR], total cholesterol [TC], low-density lipoprotein cholesterol and triglyceride), target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio [UACR]) and inflammation indices (interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hs-CRP]). RESULTS: HQQR's primary components were identified as salvianolic acid B, emodin and ferulic acid. Of the 216 participants (108 in each group), compared to the control, the intervention group exhibited significant improvements (P < 0.001) in clinic systolic blood pressure ([136.24 ± 7.63] vs [130.06 ± 8.50] mmHg), clinic diastolic blood pressure ([84.34 ± 8.72] vs [80.46 ± 6.05] mmHg), home systolic blood pressure ([131.64 ± 8.74] vs [122.36 ± 8.45] mmHg) and home diastolic blood pressure ([78.47 ± 9.53] vs [71.79 ± 6.82] mmHg). HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure: [133.75 ± 10.49] vs [132.46 ± 8.84] mmHg and 24-hour diastolic blood pressure: [84.12 ± 8.01] vs [82.11 ± 7.45] mmHg) and an improvement in HOMA-IR ([4.09 ± 1.72] vs [3.98 ± 1.44]), TC ([4.66 ± 1.47] vs [3.75 ± 1.81] mmol/L) and UACR (75.94 [5.12, 401.12] vs 45.61 [4.26, 234.26]). Moreover, HQQR demonstrated a decrease in hs-CRP (1.46 [0.10, 10.53] vs 0.57 [0.12, 3.99] mg/L) and IL-6 (6.69 [2.00, 29.74] vs 5.27 [2.00, 9.73] pg/mL), with no reported side effects (P < 0.001). CONCLUSION: This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure, glycolipid metabolism, and inflammation in patients with hypertension. TRIAL REGISTRATION: ChiCTR2000035092 (https://www.chictr.org.cn/). Please cite this article as: Xie J, Ma YL, Gui MT, Yao L, Li JH, Wang MZ, Zhou XJ, Wang YF, Zhao MY, Cao H, Lu B, Fu DY. Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension: A randomized, double-blind, placebo-controlled trial. J Integr Med 2024; 22(4): 485-493.
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Pressão Sanguínea , Medicamentos de Ervas Chinesas , Hipertensão Essencial , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Método Duplo-Cego , Hipertensão Essencial/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Adulto , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Resultado do Tratamento , Idoso de 80 Anos ou mais , Adulto JovemRESUMO
Environmental aflatoxin B1 (AFB1) exposure has been proposed to contribute to hepatocellular carcinoma by promoting liver fibrosis, but the potential mechanisms remain to be further elucidated. Extracellular vesicles (EVs) were recognized as crucial traffickers for hepatic intercellular communication and play a vital role in the pathological process of liver fibrosis. The AFB1-exposed hepatocyte-derived EVs (AFB1-EVs) were extracted, and the functional effects of AFB1-EVs on the activation of hepatic stellate cells (HSCs) were explored to investigate the molecular mechanism of AFB1 exposure-induced liver fibrogenesis. Our results revealed that an environment-level AFB1 exposure induced liver fibrosis via HSCs activation in mice, while the AFB1-EVs mediated hepatotoxicity and liver fibrogenesis in vitro and in vivo. AFB1 exposure in vitro increased PINK1/Parkin-dependent mitophagy in hepatocytes, where upregulated transcription of the PARK2 gene via p53 nuclear translocation and mitochondrial recruitment of Parkin, and promoted AFB1-EVs-mediated mitochondria-trafficking communication between hepatocytes and HSCs. The knockdown of Parkin in HepaRG cells reversed HSCs activation by blocking the mitophagy-related AFB1-EVs trafficking. This study further revealed that the hepatic fibrogenesis of AFB1 exposure was rescued by genetic intervention with siPARK2 or p53's Pifithrin-α (PFTα) inhibitors. Furthermore, AFB1-EVs-induced HSCs activation was relieved by GW4869 pharmaceutic inhibition of EVs secretion. These results revealed a novel mechanism that AFB1 exposure-induced p53-Parkin signal axis regulated mitophagy-dependent hepatocyte-derived EVs to mediate the mitochondria-trafficking intercellular communication between hepatocytes and HSCs in the local hepatotoxic microenvironment to promote the activated HSCs-associated liver fibrogenesis. Our study provided insight into p53-Parkin-dependent pathway regulation and promised an advanced strategy targeting intervention to EVs-mediated mitochondria trafficking for preventing xenobiotics-induced liver fibrosis.
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Aflatoxina B1 , Vesículas Extracelulares , Células Estreladas do Fígado , Hepatócitos , Cirrose Hepática , Mitofagia , Proteína Supressora de Tumor p53 , Ubiquitina-Proteína Ligases , Aflatoxina B1/toxicidade , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Vesículas Extracelulares/efeitos dos fármacos , Vesículas Extracelulares/metabolismo , Mitofagia/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Animais , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Camundongos , Masculino , Humanos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacosRESUMO
Transcription factors (TFs) play important roles in early embryonic development, but factors regulating TF action, relationships in signaling cascade, genome-wide localizations, and impacts on cell fate transitions during this process have not been clearly elucidated. In this study, we used uliCUT&RUN-seq to delineate a TFAP2C-centered regulatory network, showing that it involves promoter-enhancer interactions and regulates TEAD4 and KLF5 function to mediate cell polarization. Notably, we found that maternal retinoic acid metabolism regulates TFAP2C expression and function by inducing the active demethylation of SINEs, indicating that the RARG-TFAP2C-TEAD4/KLF5 axis connects the maternal-to-zygotic transition to polarization. Moreover, we found that both genomic imprinting and SNP-transferred genetic information can influence TF positioning to regulate parental gene expressions in a sophisticated manner. In summary, we propose a ternary model of TF regulation in murine embryonic development with TFAP2C as the core element and metabolic, epigenetic, and genetic information as nodes connecting the pathways.
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Implantação do Embrião , Regulação da Expressão Gênica no Desenvolvimento , Fator de Transcrição AP-2 , Fatores de Transcrição , Animais , Feminino , Camundongos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Implantação do Embrião/genética , Desenvolvimento Embrionário/genética , Redes Reguladoras de Genes , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Proteínas Musculares/metabolismo , Proteínas Musculares/genética , Regiões Promotoras Genéticas/genética , Fatores de Transcrição de Domínio TEA/metabolismo , Fator de Transcrição AP-2/metabolismo , Fator de Transcrição AP-2/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Tretinoína/metabolismoRESUMO
Background: Less research has linked the Systemic Immune Inflammatory Index (SII) with post-stroke depression (PSD). This study aims to look at any potential connections between SII and PSD. Methods: The National Health and Nutrition Examination Survey (NHANES), conducted in a population that embodied complete SII and stroke data from 2005 to 2020, was used to perform the current cross-sectional survey. A fitted smoothed curve was used to depict the nonlinear link between SII and PSD, and multiple linear regression analysis demonstrated a positive correlation between SII and PSD. Results: Multiple linear regression analysis showed that SII and PSD were markedly related [1.11(1.05, 1.17)]. Interaction tests showed that the association between SII and PSD was not statistically different between strata, and age, sex, BMI, income poverty ratio, education level, smoking status, diabetes mellitus, coronary heart disease, and heart failure did not have a significant effect on this positive association (p > 0.05 for interaction). In addition, a nonlinear association between SII and PSD was found using a two-stage linear regression model. Conclusion: The results of our research support the existence of a significant positive correlation between SII levels and PSD. Further prospective trials are required to comprehend SII, which is for the PSD thoroughly.
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BACKGROUND: The P2X7 receptor (P2X7R) is known to play a significant role in regulating various pathological processes associated with immune regulation, neuroprotection, and inflammatory responses. It has emerged as a potential target for the treatment of diseases. In addition to chemically synthesized small molecule compounds, natural products have gained attention as an important source for discovering compounds that act on the P2X7R. PURPOSE: To explore the research progress made in the field of natural product-derived compounds that act on the P2X7R. METHODS: The methods employed in this review involved conducting a thorough search of databases, include PubMed, Web of Science and WIKTROP, to identify studies on natural product-derived compounds that interact with P2X7R. The selected studies were then analyzed to categorize the compounds based on their action on the receptor and to evaluate their therapeutic applications, chemical properties, and pharmacological actions. RESULTS: The natural product-derived compounds acting on P2X7R can be classified into three categories: P2X7R antagonists, compounds inhibiting P2X7R expression, and compounds regulating the signaling pathway associated with P2X7R. Moreover, highlight the therapeutic applications, chemical properties and pharmacological actions of these compounds, and indicate areas that require further in-depth study. Finally, discuss the challenges of the natural products-derived compounds exploration, although utilizing compounds from natural products for new drug research offers unique advantages, problems related to solubility, content, and extraction processes still exist. CONCLUSION: The detailed information in this review will facilitate further development of P2X7R antagonists and potential therapeutic strategies for P2X7R-associated disorders.
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Produtos Biológicos , Antagonistas do Receptor Purinérgico P2X , Receptores Purinérgicos P2X7 , Receptores Purinérgicos P2X7/metabolismo , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Humanos , Antagonistas do Receptor Purinérgico P2X/farmacologia , Antagonistas do Receptor Purinérgico P2X/química , Transdução de Sinais/efeitos dos fármacos , AnimaisRESUMO
Adenomyosis is a poorly understood gynecological disorder lacking effective treatments. Controversy persists regarding "invagination" and "metaplasia" theories. The endometrial-myometrial junction (EMJ) connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis, but its in-depth study is just beginning. Using single-cell RNA sequencing and spatial profiling, we mapped transcriptional alterations across eutopic endometrium, lesions, and EMJ. Within lesions, we identified unique epithelial (LGR5+) and invasive stromal (PKIB+) subpopulations, along with WFDC1+ progenitor cells, supporting a complex interplay between "invagination" and "metaplasia" theories of pathogenesis. Further, we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin pathways. Cell-cell communication differed markedly between ectopic and eutopic endometrium, with aberrant signaling in lesions involving pleiotrophin, TWEAK, and WNT cascades. This study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified, dysfunctional signaling, and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.
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Adenomiose , Análise de Célula Única , Transcriptoma , Humanos , Feminino , Adenomiose/genética , Adenomiose/metabolismo , Adenomiose/patologia , Endométrio/metabolismo , Endométrio/patologia , Análise de Sequência de RNA , Miométrio/metabolismo , Miométrio/patologiaRESUMO
Yam is an important medicinal and edible dual-purpose plant with high economic value. However, nematode damage severely affects its yield and quality. One of the major effects of nematode infestations is the secondary infection of pathogenic bacteria or fungi through entry wounds made by the nematodes. Understanding the response of the symbiotic microbial community of yam plants to nematodes is crucial for controlling such a disease. In this study, we investigated the rhizosphere and how endophytic microbiomes shift after nematode infection during the tuber expansion stage in the Dioscorea opposita Thunb. cultivar Tiegun. Our results revealed that soil depth affected the abundance of nematodes, and the relative number of Meloidogyne incognita was higher in the diseased soil at a depth of 16 to 40 cm than those at a depth of 0 to 15 and 41 to 70 cm. The abundance of and interactions among soil microbiota members were significantly correlated with root-knot nematode (RKN) parasitism at various soil depths. However, the comparison of the microbial α-diversity and composition between healthy and diseased rhizosphere soil showed no difference. Compared with healthy soils, the co-occurrence networks of M. incognita-infested soils included a higher ratio of positive correlations linked to plant health. In addition, we detected a higher abundance of certain taxonomic groups belonging to Chitinophagaceae and Xanthobacteraceae in the rhizosphere of RKN-infested plants. The nematodes, besides causing direct damage to plants, also possess the ability to act synergistically with other pathogens, especially Ramicandelaber and Fusarium, leading to the development of disease complexes. In contrast to soil samples, RKN parasitism specifically had a significant effect on the composition and assembly of the root endophytic microbiota. The RKN colonization impacted a wide variety of endophytic microbiomes, including Pseudomonas, Sphingomonas, Rhizobium, Neocosmospora, and Fusarium. This study revealed the relationship between RKN disease and changes in the rhizosphere and endophytic microbial community, which may provide novel insights that help improve biological management of yam RKNs.
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Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS), is a benign histiocytosis with hyperreactive proliferation of the mononuclear phagocyte system caused by immune function abnormalities, which often occurs under the background of genetic mutations, inflammation, infection or tumors. Because the research on malignancy-associated HLH (M-HLH) is focused on hematological malignancies, reports on HLH secondary to solid tumors are rare. In this case, we report a 14-year-old girl who developed HLH during treatment for intracranial multifocal germinoma, and the disease was controlled after hormone combined with etoposide(VP-16) and other related treatments. To our knowledge, there have been no documented cases of HLH caused by intracranial multifocal germinoma.
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Colitis is a major gastrointestinal disease that threatens human health. In this study, a synbiotic composed of inulin and Pediococcus acidilactici (P. acidilactici) was investigated for its ability to alleviate dextran sulfate sodium (DSS)-induced colitis. The results revealed that the synbiotic, composed of inulin and P. acidilactici, attenuated the body weight loss and disease activity index (DAI) score in mice with DSS-mediated colitis. Determination of biochemical indicators found that the synbiotic increased anti-oxidation and alleviated inflammation in mice. Additionally, histopathological examination revealed that colonic goblet cell loss and severe mucosal damage in the model group were significantly reversed by the combination of inulin and P. acidilactici. Moreover, synbiotic treatment significantly reduced the levels of IL-1ß, TNF-α, and IL-6 in the serum of mice. Thus, a synbiotic composed of inulin and P. acidilactici has preventive and therapeutic effects on DSSinduced colitis in mice.
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Colite Ulcerativa , Colite , Pediococcus acidilactici , Simbióticos , Humanos , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Inulina/farmacologia , Sulfato de Dextrana/toxicidade , Colite/induzido quimicamente , Colo/patologia , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
Mitochondria-associated membrane (MAM) serve as crucial contact sites between mitochondria and the endoplasmic reticulum (ER). Recent research has highlighted the significance of MAM, which serve as a platform for various protein molecules, in processes such as calcium signaling, ATP production, mitochondrial structure and function, and autophagy. Cardiac diseases caused by any reason can lead to changes in myocardial structure and function, significantly impacting human health. Notably, MAM exhibits various regulatory effects to maintain cellular balance in several cardiac diseases conditions, such as obesity, diabetes mellitus, and cardiotoxicity. MAM proteins independently or interact with their counterparts, forming essential tethers between the ER and mitochondria in cardiomyocytes. This review provides an overview of key MAM regulators, detailing their structure and functions. Additionally, it explores the connection between MAM and various cardiac injuries, suggesting that precise genetic, pharmacological, and physical regulation of MAM may be a promising strategy for preventing and treating heart failure.
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This article studies Lyapunov stability for nonlinear systems based on discrete-time self-triggered impulsive control (STIC). With the help of comparison approach, some Lyapunov-based sufficient conditions guaranteeing nonZeno behavior and global asymptotic stability of nonlinear systems under STIC are derived. Different from the existing self-triggered mechanisms using implicit expressions to compute the next impulse instant, which may result in computational burden, we propose a novel discrete-time self-triggered mechanism (STM) by which the next impulse instant can be predicted directly by the information of the comparison system. Moreover, the resulting algorithm is easy to be implemented. It is shown that the designed STIC strategy can not only achieve a tradeoff between computational complexity, communication resource usage and control performance, but also has strong robustness and flexibility. Finally, an illustrative simulation is provided showing the effectiveness of the results.
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Various post-stroke dysfunctions often result in poor long-term outcomes for stroke survivors, but the effect of conventional treatments is limited. In recent years, lots of studies have confirmed the effect of repetitive transcranial magnetic stimulation (rTMS) in stroke rehabilitation. As a new pattern of rTMS, theta burst stimulation (TBS) was proved recently to yield more pronounced and long-lasting after-effects than the conventional pattern at a shorter stimulation duration. To explore the role of TBS in stroke rehabilitation, this review summarizes the existing evidence from all the randomized controlled trials (RCTs) so far on the efficacy of TBS applied to different post-stroke dysfunctions, including cognitive impairment, visuospatial neglect, aphasia, dysphagia, spasticity, and motor dysfunction. Overall, TBS promotes the progress of stroke rehabilitation and may serve as a preferable alternative to traditional rTMS. However, it's hard to recommend a specific paradigm of TBS due to the limited number of current studies and their heterogeneity. Further high-quality clinical RCTs are needed to determine the optimal technical settings and intervention time in stroke survivors.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Estimulação Magnética Transcraniana , Acidente Vascular Cerebral/complicações , Fatores de TempoRESUMO
During early adolescence, parental influence diminishes, whereas friends' influence increases in shaping emotion regulation abilities. However, it is unclear how parents and friends jointly contribute to emotion regulation abilities and how their joint effects vary by gender. This study examines fathers, mothers, and friends as simultaneous emotional socializers and considers the young adolescents' gender. The analysis drew on 438 young Chinese adolescents (55.7% girls, Mage = 11.39, SD = 1.28) who participated in a longitudinal survey over one year. Results showed that parental and friend emotion socialization have both distinct and joint effects. Friends' responses provided a unique contribution to emotion regulation abilities across gender, whereas parents' responses displayed unique contributions among girls. In predicting girls' emotion regulation abilities, mothers' supportive responses explained the additional variance beyond friends' responses, whereas fathers' unsupportive responses moderated the predictive power of friends' responses. These findings clarify emotion-related socialization theories and emphasize the importance of gender specific prevention programs focusing on emotion socialization from both parents and friends in early adolescence.