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1.
Fish Shellfish Immunol ; : 109531, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38604479

RESUMO

In this study, we present the first cloning and identification of perforin (MsPRF1) in largemouth bass (Micropterus salmoides). The full-length cDNA of MsPRF1 spans 1572 base pairs, encoding a 58.88 kDa protein consisting of 523 amino acids. Notably, the protein contains MACPF and C2 structural domains. To evaluate the expression levels of MsPRF1 in various healthy largemouth bass tissues, real-time quantitative PCR was employed, revealing the highest expression in the liver and gut. After the largemouth bass were infected by Nocardia seriolae, the mRNA levels of MsPRF1 generally increased within 48 h. Remarkably, the recombinant protein MsPRF1 exhibits inhibitory effects against both Gram-negative and Gram-positive bacteria. Additionally, the largemouth bass showed a higher survival rate in the N. seriolae challenge following the intraperitoneal injection of rMsPRF1, with observed reductions in the tissue bacterial loads. Moreover, rMsPRF1 demonstrated a significant impact on the phagocytic and bactericidal activities of largemouth bass MO/MΦ cells, concurrently upregulating the expression of pro-inflammatory factors. These results demonstrate that MsPRF1 has a potential role in the immune response of largemouth bass against N. seriolae infection.

2.
Curr Biol ; 34(7): R275-R278, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38593770

RESUMO

Collective cell migration is a key cellular process in development and disease. A new study reports that ER stress is induced during collective cell migration and an intrinsic mechanism prevents migratory cells from over-reacting to ER stress.


Assuntos
Movimento Celular
3.
Bioorg Chem ; 147: 107400, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38688196

RESUMO

Although certain members of the Ubiquitin-specific peptidases (USPs) have been recognized as promising therapeutic targets for various diseases, research progress regarding USP21 has been relatively sluggish in its early stages. USP21 is a crucial member of the USPs subfamily, involved in diverse cellular processes such as apoptosis, DNA repair, and signal transduction. Research findings from the past decade demonstrate that USP21 mediates the deubiquitination of multiple well-known target proteins associated with critical cellular processes relevant to both disease and homeostasis, particularly in various cancers.This reviewcomprehensively summarizes the structure and biological functions of USP21 with an emphasis on its role in tumorigenesis, and elucidates the advances on the discovery of tens of small-molecule inhibitors targeting USP21, which suggests that targeting USP21 may represent a potential strategy for cancer therapy.

4.
NPJ Biofilms Microbiomes ; 10(1): 40, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605016

RESUMO

Increasing evidence infers that some complex diseases are attributed to co-infection with multiple pathogens, such as shrimp white feces syndrome (WFS); however, there is a lack of experimental evidence to validate such causal link. This deficiency further impedes rational design of probiotics to elicit desired benefits to shrimp WFS resistance. Herein, we validated the causal roles of Vibrio fluvialis, V. coralliilyticus and V. tubiashii (in a ratio of 7:2:1) in shrimp WFS etiology, which fully satisfied Koch's postulates. Correspondingly, we precisely designed four antagonistic strains: Ruegeria lacuscaerulensis, Nioella nitratireducens, Bacillus subtilis and Streptomyces euryhalinus in a ratio of 4:3:2:1, which efficiently guarded against WFS. Dietary supplementation of the probiotics stimulated beneficial gut populations, streptomycin, short chain fatty acids, taurine metabolism potentials, network stability, tight junction, and host selection, while reducing turnover rate and average variation degree of gut microbiota, thereby facilitating ecological and mechanical barriers against pathogens. Additionally, shrimp immune pathways, such as Fcγ R-mediated phagocytosis, Toll-like receptor and RIG-I-like receptor signaling pathways conferring immune barrier, were activated by probiotics supplementation. Collectively, we establish an updated framework for precisely validating co-infection with multiple pathogens and rationally designing antagonistic probiotics. Furthermore, our findings uncover the underlying beneficial mechanisms of designed probiotics from the probiotics-gut microbiome-host immunity axis.


Assuntos
Coinfecção , Microbioma Gastrointestinal , Probióticos , Humanos , Fezes
5.
Microorganisms ; 12(3)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38543573

RESUMO

Glugea plecoglossi is an obligate intracellular microsporidium, which poses a significant threat to ayu (Plecoglossus altivelis). In vitro cultivation models are invaluable tools for investigating intracellular microorganisms, including G. plecoglossil. In this study, we attempted to in vitro cultivate G. plecoglossi using primary cultures derived from ayu monocytes/macrophages (MO/MΦ), a murine-derived macrophage cell line RAW264.7, and the epithelioma papulosum cyprini (EPC) cell line. The results demonstrated that MO/MΦ infected with spores exhibited a pronounced immune response which was presented by rapidly high expression levels of inflammatory cytokines, such as PaIL-1ß, PaTNF-α, PaIL-10, and PaTGF-ß, and detached within 96 h post-infection (hpi). Infected RAW264.7 cells remained capable of stable passage yet exhibited cellular deformation with a decrease in intracellular spores occurring around 8 days post-infection (dpi). In contrast, EPC cells promised a substantial parasite population, and the cytokine expression levels returned to normal by 8 dpi. In addition, G. plecoglossi spores recovered from EPC cells could infect young ayu, suggesting that EPC cells might be used as an in vitro cultivation system for G. plecoglossi.

6.
Cell Mol Biol Lett ; 29(1): 32, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443798

RESUMO

RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid-protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure-activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy.


Assuntos
Descoberta de Drogas , Epigênese Genética , Homeostase , RNA , RNA Mensageiro
7.
bioRxiv ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38370767

RESUMO

Single-cell technologies have emerged as a transformative technology enabling high-dimensional characterization of cell populations at an unprecedented scale. The data's innate complexity and voluminous nature pose significant computational and analytical challenges, especially in comparative studies delineating cellular architectures across various biological conditions (i.e., generation of sample level distance matrices). Optimal Transport (OT) is a mathematical tool that captures the intrinsic structure of data geometrically and has been applied to many bioinformatics tasks. In this paper, we propose QOT (Quantized Optimal Transport), a new method enables efficient computation of sample level distance matrix from large-scale single-cell omics data through a quantization step. We apply our algorithm to real-world single-cell genomics and pathomics datasets, aiming to extrapolate cell-level insights to inform sample level categorizations. Our empirical study shows that QOT outperforms OT-based algorithms in terms of accuracy and robustness when obtaining a distance matrix at the sample level from high throughput single-cell measures. Moreover, the sample level distance matrix could be used in downstream analysis (i.e. uncover the trajectory of disease progression), highlighting its usage in biomedical informatics and data science.

8.
BMC Cancer ; 24(1): 253, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395798

RESUMO

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.


Assuntos
Desnutrição , Neoplasias Gástricas , Humanos , Caquexia/diagnóstico , Caquexia/etiologia , Prognóstico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Liderança , Velocidade de Caminhada , Desnutrição/complicações , Desnutrição/diagnóstico , Estado Nutricional , Força da Mão , Avaliação Nutricional
9.
Nat Commun ; 15(1): 354, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191573

RESUMO

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN - a multi-view, weakly-supervised deep clustering method - which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer's disease and brain endophenotypes associated with hypertension, from MRI and single nucleotide polymorphism data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-associated neuroimaging phenotypes.


Assuntos
Doença de Alzheimer , Neuroimagem , Humanos , Endofenótipos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Encéfalo/diagnóstico por imagem , Análise por Conglomerados
10.
Fish Shellfish Immunol ; 145: 109364, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199264

RESUMO

Micropterus salmoides rhabdovirus (MSRV) is one of the main pathogens of largemouth bass, leading to serious economic losses. The G protein, as the only envelope protein present on the surface of MSRV virion, contains immune-related antigenic determinants, thereby becoming the primary target for the design of MSRV vaccines. Here, we displayed the G protein on the surface of yeast cells (named EBY100/pYD1-G) and conducted a preliminary assessment of the protective efficacy of the recombinant yeast vaccine. Upon oral vaccination, a robust immune response was observed in systemic and mucosal tissue. Remarkably, following the MSRV challenge, the relative percent survival of EBY100/pYD1-G treated largemouth bass significantly increased to 66.7 %. In addition, oral administration inhibited viral replication and alleviated the pathological symptoms of MSRV-infected largemouth bass. These results suggest that EBY100/pYD1-G could be used as a potential oral vaccine against MSRV infection.


Assuntos
Bass , Doenças dos Peixes , Rhabdoviridae , Animais , Saccharomyces cerevisiae , Vacinação , Proteínas Fúngicas , Vacinas Sintéticas
11.
Fish Shellfish Immunol ; 144: 109284, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38092092

RESUMO

Micropterus salmoides rhabdovirus (MSRV) is a significant viral pathogen in largemouth bass aquaculture, causing substantial annual economic losses. However, effective prevention methods remain elusive for various reasons. Medicinal plant extracts have emerged as valuable tools in preventing and managing aquatic animal diseases. Thus, the search for immunomodulators with straightforward, safe structures in plant extracts is imperative to ensure the continued health and growth of the largemouth bass industry. In our research, we employed epithelioma papulosum cyprinid (EPC) cells and largemouth bass as models to assess the anti-MSRV properties and immunomodulatory effects of ten plant-derived bioactive compounds. Among them, rhein demonstrated noteworthy potential, exhibiting a 75 % reduction in viral replication in vitro at a concentration of 50 mg/L. Furthermore, rhein pre-treatment significantly inhibited MSRV genome replication in EPC cells, with the highest inhibition rate reaching 64.8 % after 24 h, underscoring rhein's preventive impact against MSRV. Likewise, rhein displayed remarkable therapeutic effects on EPC cells during the early stages of MSRV infection, achieving a maximum inhibition rate of 85.6 % in viral replication. Subsequent investigations unveiled that rhein, with its consistent activity, effectively mitigated cytopathic effects (CPE) and nuclear damage induced by MSRV infection. Moreover, it restrained mitochondrial membrane depolarization and reduced the apoptosis rate by 38.8 %. In vivo experiments reinforced these findings, demonstrating that intraperitoneal injection of rhein enhanced the expression levels of immune related genes in multiple organs, hindered virus replication, and curtailed the mortality rate of MSRV-infected largemouth bass by 29 %. Collectively, our study endorses the utility of rhein as an immunomodulator to combat MSRV infections in largemouth bass. This not only underscores the potential of rhein as a broad-spectrum antiviral and means to bolster the immune response but also highlights the role of apoptosis as an immunological marker, making it an invaluable addition to the armamentarium against aquatic viral pathogens.


Assuntos
Bass , Doenças dos Peixes , Infecções por Rhabdoviridae , Rhabdoviridae , Animais , Fatores Imunológicos/metabolismo , Poder Psicológico , Doenças dos Peixes/prevenção & controle
12.
Graefes Arch Clin Exp Ophthalmol ; 262(1): 323-330, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37490104

RESUMO

PURPOSE: We aimed to explore the effects of the ciliary sulcus angle (CSA) on accurate prediction of the vault after phakic implantable collamer lens (EVO ICL Model V4c) using the KS formula. METHODS: Patients were classified according to the size of CSA: group A, narrow angle (CSA < 30°); group B, normal angle (CSA = 30-90°); and group C, wide angle (CSA > 90°). Further, differences between the actual vault dimensions at 3 months postoperatively and the preoperatively predicted vault dimensions in the three groups were analyzed. RESULTS: This study included 223 eyes of 223 individuals. In groups A-C, the difference in the preoperative vault dimensions of the three groups predicted with the KS formula was not statistically significant (P = 0.056). The actual vault dimensions at 3 months postoperatively were significantly different between the three groups (P < 0.001). Moreover, the difference between the actual and predicted vaults by the KS formula was statistically significant (P < 0.001). In the 3 months, after surgery, the percentages of patients with a low vault (< 250 µm) were 0%, 3%, and 29% in groups A, B, and C, respectively. Further, the percentages of patients with an ideal vault (250-750 µm) in the postoperative period were 66%, 84%, and 71% in groups A, B, and C, respectively. Finally, the percentages of patients with a high vault (> 750 µm) in the postoperative period were 34%, 13%, and 0% in groups A, B, and C, respectively. Notably, the distribution of the vault among the three groups was statistically significant (P < 0.001). CONCLUSION: The size of CSA significantly affects the predictiveness of the vault by the KS formula, with the most pronounced effect on the angles < 30° and > 90°. Therefore, CSA should be considered when selecting the lens size using the KS formula preoperatively. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065501.


Assuntos
Cristalino , Lentes Intraoculares Fácicas , Humanos , Implante de Lente Intraocular/métodos , Acuidade Visual , Olho , Estudos Retrospectivos
13.
Life Sci ; 336: 122310, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38013140

RESUMO

AIMS: Qipian® is a commercialized agent composed of extracts of three genera of commensal bacteria, and its mechanism of action on asthma is unclear. This study aimed to examine the impact of Qipian® on airway inflammation and investigate the underlying mechanisms. MATERIALS AND METHODS: Qipian® or dexamethasone (DEX) was administered before OVA challenge in an ovalbumin-induced asthma mouse model, and then asthmatic symptoms were observed and scored. Samples of lung tissues, blood, and bronchoalveolar lavage fluid (BALF) were collected, and eosinophils (Eos), immunoglobins (Igs), and type 1 T helper (Th1)/Th2 cell cytokines were measured. Mucus production in the lung was assessed by periodic acid-Schiff (PAS) staining. The effects of Qipian® on dendritic and T regulatory (Treg) cells were investigated using flow cytometry. KEY FINDINGS: The short-term administration of Qipian® significantly inhibited the cardinal features of allergic asthma, including an elevated asthmatic behaviour score, airway inflammation and immune response. Histological analysis of the lungs showed that Qipian® attenuated airway inflammatory cell infiltration and mucus hyperproduction. Qipian® restored Th1/Th2 imbalance by decreasing interleukin (IL)-4, IL-5, and IL-13 while increasing interferon (IFN)-γ and IL-10. Further investigation revealed that Qipian® treatment induced the upregulation of CD4+CD25+Foxp3+ Treg cells and CD103+ DCs and downregulation of tachykinins neurokinin A (NKA) and NKB in the lung. SIGNIFICANCE: Our findings suggested that short-term treatment with Qipian® could alleviate inflammation in allergic asthma through restoring the Th1/Th2 balance by recruiting Treg cells to airways and inducing the proliferation of CD103+ DCs, which actually provides a new treatment option for asthma.


Assuntos
Asma , Lisados Bacterianos , Animais , Camundongos , Ovalbumina , Asma/metabolismo , Pulmão/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Citocinas , Líquido da Lavagem Broncoalveolar , Imunidade , Bactérias , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças
14.
Osteoarthritis Cartilage ; 32(1): 66-81, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37802465

RESUMO

OBJECTIVE: This study aimed to explore the specific function of M2 macrophages in intervertebral disc degeneration (IDD). METHODS: Intervertebral disc (IVD) samples from normal (n = 4) and IDD (n = 6) patients were collected, and the expression of M2-polarized macrophage marker, CD206, was investigated using immunohistochemical staining. Nucleus pulposus cells (NPCs) in a TNF-α environment were obtained, and a mouse caudal IVD puncture model was established. Mice with Rheb deletions, specifically in the myeloid lineage, were generated and subjected to surgery-induced IDD. IDD-induced damage and cell apoptosis were measured using histological scoring, X-ray imaging, immunohistochemical staining, and TdT-mediated dUTP nick end labeling (TUNEL) assay. Finally, mice and NPCs were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in IDD. RESULTS: Accumulation of CD206 in human and mouse IDD tissues was detected. Rheb deletion in the myeloid lineage (RheBcKO) increased the number of CD206+ M2-like macrophages (mean difference 18.6% [15.7-21.6%], P < 0.001), decreased cell apoptosis (mean difference -15.6% [-8.9 to 22.2%], P = 0.001) and attenuated the IDD process in the mouse IDD model. NPCs treated with Rspo2 displayed increased extracellular matrix catabolism and apoptosis; co-culture with a conditioned medium derived from RheBcKO mice inhibited these changes. Anti-Rspo2 treatment in the mouse caudal IVD puncture model exerted protective effects against IDD. CONCLUSIONS: Promoting CD206+ M2-like macrophages could reduce Rspo2 secretion, thereby alleviating experimental IDD. Rheb deletion may help M2-polarized macrophages accumulate and attenuate experimental IDD partially by inhibiting Rspo2 production. Hence, M2-polarized macrophages and Rspo2 may serve as therapeutic targets for IDD.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Camundongos , Animais , Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Apoptose , Modelos Animais de Doenças , Macrófagos/metabolismo
15.
Fish Shellfish Immunol ; 145: 109308, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38122956

RESUMO

Galectin-9, a tandem-repeat galectin, plays an important role in the regulation of innate immune response against various microbial infections. Here, galectin-9 from mudskipper (Boleophthalmus pectinirostris) was identified and named as BpGal-9. Putative BpGal-9 contains two conserved carbohydrate recognition domains (CRDs), one CRD within N-terminal (N-CRD) and the other one within C-terminal (C-CRD). Multi-alignment analysis indicated that BpGal-9 shared the highest amino acid sequence identity of 64.3 % with that of Southern platyfish (Xiphophorus maculatus). Phylogenetic analysis showed that BpGal-9 grouped tightly with other teleosts galectin-9 and was most closely related to that of Southern platyfish. BpGal-9 transcripts were more abundant in the intestine, and its expression upregulated significantly in the intestine, kidney, spleen, gills, and skin after Edwardsiella tarda infection. Meanwhile, BpGal-9 expression significantly increased in hemocytes and serum of mudskipper infected by E. tarda. The recombinant BpGal-9 (rBpGal-9) and rBpGal-9C-CRD could agglutinate all tested bacteria, whereas rBpGal-9N-CRD could only agglutinate three kinds of bacteria. When targeting the same bacteria, rBpGal-9 showed stronger agglutinating activities than rBpGal-9C-CRD or rBpGal-9N-CRD. In addition, the induction effect of three recombinant proteins on the mRNA expression of anti-inflammatory cytokines (BpIL-10 and BpTGF-ß) was better than that on the pro-inflammatory cytokines (BpIL-1ß and BpTNF-α). Our result suggested that the N-CRD and C-CRD of galectin-9 contribute differently to its multiple functions in innate immunity in teleosts.


Assuntos
Proteínas de Peixes , Perciformes , Animais , Proteínas de Peixes/genética , Filogenia , Alinhamento de Sequência , Peixes , Perciformes/genética , Imunidade Inata/genética , Citocinas/genética , Galectinas/genética
16.
Proc Natl Acad Sci U S A ; 120(52): e2300842120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38127979

RESUMO

Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and appendage development, while pathways of breast cancer indicate potential interplays between brain metastasis and PSCs associated with neurodegeneration and dementia. Using support vector machines, multi-scale PSCs effectively derive imaging signatures of several brain diseases. Our results elucidate genetic and biological underpinnings that influence structural covariance patterns in the human brain.


Assuntos
Neoplasias Encefálicas , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/patologia , Mapeamento Encefálico/métodos , Genômica , Neoplasias Encefálicas/patologia
17.
J Gastrointest Oncol ; 14(5): 2039-2047, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37969839

RESUMO

Background: Preoperative albumin-bilirubin (ALBI) grade has been proposed and applied in recent years to evaluate the prognosis of liver cancer, but its role in gastric cancer (GC) is still unclear. This research aimed to examine the prognostic value of ALBI grade after gastrectomy among patients with GC complicated with metabolic syndrome (MetS). Methods: There were 628 patients who received radical resection for GC. Laboratory data and short-term results were collected prospectively, and preoperative ALBI grades were calculated from the albumin and bilirubin levels. The appropriate ALBI cutoff value was calculated by receiver operating characteristic (ROC) curve analysis, which we used to put patients into high (>-2.54) and low (≤-2.54) ALBI grade groups. The differences between the short-term complication rates of the two groups were analyzed with the chi-square test. Results: Of the included patients, 133 (21.2%) and 495 (78.8%) had high and low ALBI grades, respectively. A high ALBI grade (P=0.001), body mass index (BMI) ≥25 kg/m2 (P=0.001), and hypertension (P=0.018) were independent risk factors for postoperative complications. In GC patients with and without MetS, the high ALBI subgroup showed more overall complications than the low ALBI subgroup (P=0.028 and P=0.001). Among GC patients with MetS, those with a high ALBI grade showed a higher incidence of serious complications than those with a low ALBI grade (P=0.001); a similar, nonsignificant trend occurred in non-MetS patients (P=0.153). Conclusions: The preoperative ALBI grade is important in the prognosis of GC patients with MetS after gastrectomy. GC patients with MetS can lower their incidence of serious complications by adjusting their preoperative ALBI grade.

18.
Aquat Toxicol ; 265: 106763, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37980848

RESUMO

Microcystins (MCs) are biologically active cyclic heptapeptide compounds released by cyanobacteria in water bodies, and MC-LR is one of the most widespread and toxic isoforms. It frequently poses a serious threat to Penaeus vannamei aquaculture. Our previous study revealed that the supplementation of Lactobacillus plantarum Ep-M17 has a probiotic effect on P. vannamei health and whether Ep-M17 can alleviate the stressful effects of MC-LR on shrimp remains unclear. Therefore, in the present work, shrimp were fed MC-LR alone or combined with Ep-M17 for six weeks, and then evaluated the effects on histology, enzyme activity, gene expression, and intestinal flora. The results showed that MC-LR stress lead to slow growth and reduced survival rates in shrimp. However, feeding Ep-M17 significantly increased both the growth rate and survival rate. Meanwhile, MC-LR stress caused severe tissue damage in the hepatopancreas and intestines of shrimp, but Ep-M17 significantly reduced the toxic effects and protected the integrity of these tissues. Additionally, Ep-M17 significantly enhanced the activities of antioxidant enzymes and digestive enzymes, and induced higher expression of immune-related genes, thereby promoting the digestive and immune responses in shrimp. Furthermore, MC-LR stress disrupted the intestinal flora in shrimp intestines, while the use of Ep-M17 significantly increased the abundance of immune- and metabolism-related bacteria and inhibited the growth of pathogenic bacteria to maintain intestinal flora balance and intestinal health. In conclusion, our results indicate that Ep-M17 can reduce the toxic effect of MC-LR on shrimp and has a positive function in the prevention and control of shrimp diseases caused by MC-LR.


Assuntos
Cianobactérias , Microbioma Gastrointestinal , Lactobacillus plantarum , Penaeidae , Poluentes Químicos da Água , Animais , Lactobacillus plantarum/metabolismo , Microcistinas/toxicidade , Microcistinas/metabolismo , Penaeidae/fisiologia , Poluentes Químicos da Água/toxicidade , Cianobactérias/metabolismo
19.
Heliyon ; 9(10): e21067, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37916112

RESUMO

It is challenging to manage schizophrenic catatonia and comorbid chronic intestinal pseudo-obstruction (CIPO). The pathology of catatonia is unclear. There are few reports or research on this issue. In this case, we present a middle-aged woman diagnosed with schizophrenia with catatonic features and comorbid CIPO. In the treatment process, modified electroconvulsive therapy (mECT) improved her stupor and CIPO partially. Lorazepam alleviated her stupor and CIPO completely. It is the first report describing complete remission with lorazepam in patient suffering from comorbid schizophrenic catatonia and CIPO, which may benefit the exploration of pathophysiology and treatment of comorbidity of schizophrenia with catatonia and CIPO.

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