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1.
World J Gastrointest Oncol ; 16(8): 3600-3623, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39171160

RESUMO

BACKGROUND: Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled. AIM: To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps. METHODS: Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators. RESULTS: The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella, Plesiomonas, and Cronobacter, was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones. CONCLUSION: These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.

2.
Nat Commun ; 15(1): 7096, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39154092

RESUMO

The intratumor microbiome imbalance in pancreatic cancer promotes a tolerogenic immune response and triggers immunotherapy resistance. Here we show that Lactobacillus rhamnosus GG probiotics, outfitted with a gallium-polyphenol network (LGG@Ga-poly), bolster immunotherapy in pancreatic cancer by modulating microbiota-immune interactions. Upon oral administration, LGG@Ga-poly targets pancreatic tumors specifically, and selectively eradicates tumor-promoting Proteobacteria and microbiota-derived lipopolysaccharides through a gallium-facilitated disruption of bacterial iron respiration. This elimination of intratumor microbiota impedes the activation of tumoral Toll-like receptors, thus reducing immunosuppressive PD-L1 and interleukin-1ß expression by tumor cells, diminishing immunotolerant myeloid populations, and improving the infiltration of cytotoxic T lymphocytes in tumors. Moreover, LGG@Ga-poly hampers pancreatic tumor growth in both preventive and therapeutic contexts, and amplifies the antitumor efficacy of immune checkpoint blockade in preclinical cancer models in female mice. Overall, we offer evidence that thoughtfully designed biomaterials targeting intratumor microbiota can efficaciously augment immunotherapy for the challenging pancreatic cancer.


Assuntos
Gálio , Lacticaseibacillus rhamnosus , Microbiota , Neoplasias Pancreáticas , Polifenóis , Probióticos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/microbiologia , Animais , Probióticos/administração & dosagem , Camundongos , Feminino , Humanos , Lacticaseibacillus rhamnosus/imunologia , Polifenóis/farmacologia , Microbiota/imunologia , Microbiota/efeitos dos fármacos , Linhagem Celular Tumoral , Imunoterapia/métodos , Camundongos Endogâmicos C57BL , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Linfócitos T Citotóxicos/imunologia
3.
Immunity ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39163866

RESUMO

Despite decades of antibody research, it remains challenging to predict the specificity of an antibody solely based on its sequence. Two major obstacles are the lack of appropriate models and the inaccessibility of datasets for model training. In this study, we curated >5,000 influenza hemagglutinin (HA) antibodies by mining research publications and patents, which revealed many distinct sequence features between antibodies to HA head and stem domains. We then leveraged this dataset to develop a lightweight memory B cell language model (mBLM) for sequence-based antibody specificity prediction. Model explainability analysis showed that mBLM could identify key sequence features of HA stem antibodies. Additionally, by applying mBLM to HA antibodies with unknown epitopes, we discovered and experimentally validated many HA stem antibodies. Overall, this study not only advances our molecular understanding of the antibody response to the influenza virus but also provides a valuable resource for applying deep learning to antibody research.

4.
Oral Dis ; 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39155514

RESUMO

OBJECTIVES: This study aimed to investigate the expression and biological significance of Semenogelin 1 (SEMG1), a member of the cancer-testis antigen family, in oral squamous cell carcinoma (OSCC). Further, we explored its potential association with metabolism-related molecules. METHODS: SEMG1 expression levels in OSCC were determined through immunohistochemistry, flow cytometry, and Western blot analyses. To decipher the biological implications of SEMG1 in OSCC, the CAL27 OSCC cell line was either stably overexpressed with SEMG1 or subjected to SEMG1-shRNA knockdown. The relationship between clinicopathological parameters and SEMG1 expression in OSCC patients was also assessed. RESULTS: SEMG1 was found to be overexpressed in OSCC, though its expression was not influenced by the pathological grade. The fluorescent dihydroethidium assay indicated that SEMG1 augmented reactive oxygen species production. The mitochondrial membrane potential assay suggested a significant upregulation of mitochondrial membrane potential by SEMG1. Cell cycle assessments highlighted that SEMG1 overexpression led to a notable rise in cells entering the S-phase. Additionally, a strong correlation between SEMG1 expression and both ENO1 and PKM2 expression in OSCC was observed. CONCLUSIONS: The findings underscore the elevated expression of SEMG1 in OSCC and its contributory role in the tumorigenesis of OSCC patients.

5.
Nano Lett ; 24(33): 10362-10371, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39133195

RESUMO

Adoptive cell therapies for solid tumors are usually limited by off-target antigens, incapable tissue infiltration, and cell function exhaustion. In contrast, bacterial cells possess the inherent competencies of preferential tumor targeting, deep tissue penetration, and high intratumoral bioactivity and represent promising alternatives to overcome these challenges. Here, a sialic-acid-responsive regulatory gene circuit is engineered into Escherichia coli MG1655 to express cytolysin of hemolysin E (HlyE). Furthermore, sialidases are bioorthogonally decorated onto the surface of azido-functionalized bioengineered bacteria for recognizing tumor sialoglycans and cleaving their sialosides into free sialic acids. As chemical inducers, sialic acids feedbackingly activate the bacterial gene circuit to produce HlyE and lyse tumor cells. This study mimics the tumor antigen-induced cytotoxin production and cell lysis that occurs in chimeric antigen receptor T (CAR-T) cells yet surmounts the intrinsic limitations of adoptive cell therapies. Moreover, sialidase-mediated tumor cell desialylation also reverses the immunosuppressive effect of glycoimmune checkpoints and further improves the therapeutic effect of solid tumors.


Assuntos
Escherichia coli , Neoplasias , Neuraminidase , Neuraminidase/genética , Neuraminidase/metabolismo , Humanos , Escherichia coli/genética , Animais , Neoplasias/terapia , Camundongos , Linhagem Celular Tumoral , Proteínas Hemolisinas/química , Receptores de Antígenos Quiméricos/imunologia , Imunoterapia Adotiva
6.
Adv Rheumatol ; 64(1): 55, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107865

RESUMO

BACKGROUND: In 2021, an EULAR task force published a definition of difficult-to-treat rheumatoid arthritis (D2T RA). Our current knowledge of D2T RA with the EULAR definition is based on European and Asian cohorts, and no North American cohort has yet to be published. The aim of this study was to compare D2T RA patients to non-D2T RA who are good responders to advanced therapy, and to describe their evolution in an university health center patient cohort. METHODS: This is a retrospective single centre study of the medical records of all adults with RA on at least one biologic or target synthetic DMARD (b/tsDMARD). D2T RA group was defined according to the EULAR definition of D2T RA. The non-D2T RA group was defined as a b/tsDMARD good responder who had low-disease activity or remission for at least one year on 1 or 2 b/tsDMARD mechanism of action. We compared the patients' comorbidities, and history of b/tsDMARD use. Descriptive statistics and proportions were calculated. Kaplan-Meier analysis with log-rank test was used to estimate and compare median survival. RESULTS: Among the 417 patients, 101 (24%) were D2T RA and 316 (76%) were non-D2T RA. D2T RA group was slightly younger (63 ± 9 years versus 65 ± 12 years, p = 0.045), more likely to have concomitant non-inflammatory pain (28% versus 8%, p < 0.0001) and to discontinue at least one b/tsDMARD due to intolerance (39% versus 10%, p < 0.0001). In the D2T RA group, JAK inhibitors were associated with longer drug continuation when used as the third b/tsDMARD. Fewer patients were using corticosteroid at their most recent follow-up in this Canadian cohort compared to others (16% versus from 29 to 74%). CONCLUSION: Concomitant non-inflammatory pain was more prevalent in D2T RA patients compared to b/tsDMARD good responder non-D2T RA patients. Steroid-sparing strategies is possible even in D2T RA patients. Future prospective research may compare JAK inhibitors with other mechanisms of action in D2T RA.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Estudos Retrospectivos , Antirreumáticos/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Produtos Biológicos/uso terapêutico , Estimativa de Kaplan-Meier , Estudos de Coortes , Indução de Remissão , Adulto , Comorbidade
7.
Asian J Androl ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107962

RESUMO

ABSTRACT: Recent evidence suggests that low-intensity extracorporeal shock wave therapy (Li-ESWT) is a promising treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its safety in pelvic organs, particularly prostate tissues and cells, remains unclear. The current study evaluates the risks of prostate cell damage or oncogenesis following the administration of Li-ESWT for prostatitis. To this end, a robust in vitro model (Cell Counting Kit-8 [CCK-8] assay, clone formation assay, cell scratch assay, lactate dehydrogenase [LDH] release assay, flow cytometry, and immunoblotting assay) was designed to examine the effects of Li-ESWT on cell proliferation, clonogenicity, migration, membrane integrity, and DNA damage. Exome sequencing of Li-ESWT-treated cells was performed to determine the risk of carcinogenesis. Furthermore, an in vivo rat model (n = 20) was employed to assess the effects of Li-ESWT on cancer biomarkers (carcinoembryonic antigen [CEA], Ki67, proliferating cell nuclear antigen [PCNA], and gamma-H2A histone family member X, phosphorylation of the H2AX Ser-139 [γ-H2AX]) in prostate tissue. Based on our findings, Li-ESWT promotes cellular growth and motility without inducing significant cell membrane or DNA damage or alterations. Genetic analyses did not demonstrate an increase in mutations, and no damage to prostate tissue or upregulation of cancer biomarkers was detected in vivo. This comprehensive in vitro and in vivo assessment confirms the safety of Li-ESWT in managing prostate disorders.

8.
Bioanalysis ; 16(11): 535-544, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-39088034

RESUMO

Aim: A new, selective and simple UPLC-MS/MS method was developed and validated for the determination of lifitegrast in human plasma and tear in order to obtain PK data. Materials & methods: Lifitegrast-d4 solutions were added in the samples, and then were extracted and transferred to a UPLC vial. Results: The respective working ranges were 25.00-2000.00 pg/ml in plasma and 4.00-1000.00 µg/ml in tear. The fully validated method complied with existing regulatory criteria for accuracy and precision, recovery, etc. It was applied to plasma and tear samples, which were from a clinical study, successfully. Conclusion: This method is useful in the evaluation of lifitegrast in plasma and tear.


[Box: see text].


Assuntos
Espectrometria de Massas em Tandem , Lágrimas , Humanos , Espectrometria de Massas em Tandem/métodos , Lágrimas/química , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massa com Cromatografia Líquida
9.
Vet Microbiol ; 297: 110199, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39096789

RESUMO

Japanese encephalitis virus (JEV) is a mosquito-borne, zoonotic orthoflavivirus causing human encephalitis and reproductive disorders in pigs. Cell-intrinsic antiviral restriction factors are the first line of defense that prevent a virus from establishing a productive infection, while the molecular mechanism of the virus-host interaction is still not fully understood. Our in vitro experiments demonstrated that the Solute Carrier Family 25 Member 12 (SLC25A12) interacted with the JEV nonstructural protein 1 (NS1) and inhibited JEV replication. Furthermore, we showed that knockdown or knockout of SLC25A12 promoted JEV replication, while overexpression of SLC25A12 repressed viral replication. Finally, we demonstrated that SLC25A12 increased IRF7 mRNA levels, which promoted IFN-ß expression and subsequently induced antiviral effects. Collectively, our study revealed that SLC25A12 interacted with NS1, inhibiting viral RNA synthesis and transcription and enhancing type I interferon induction for antiviral effects.

10.
Artigo em Inglês | MEDLINE | ID: mdl-39011845

RESUMO

OBJECTIVES: To establish the epidemiology cut-off (ECOFF) values of eravacycline against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii and Staphylococcus aureus, from a multi-centre study in China. METHODS: We collected 2500 clinical isolates from five hospitals in China from 2017 to 2020. The MICs of eravacycline were determined using broth microdilution. The ECOFF values of eravacycline against the five species commonly causing cIAIs were calculated using visual estimation and ECOFFinder following the EUCAST guideline. RESULTS: The MICs of eravacycline against all the strains were in the range of 0.004-16 mg/L. The ECOFF values of eravacycline were 0.5 mg/L for E. coli, 2 mg/L for K. pneumonia and E. cloacae, and 0.25 mg/L for A. baumannii and S. aureus, consistent with the newest EUCAST publication of eravacycline ECOFF values for the populations. No discrepancy was found between the visually estimated and 99.00% ECOFF values calculated using ECOFFinder. CONCLUSIONS: The determined ECOFF values of eravacycline against the five species can assist in distinguishing wild-type from non-wild-type strains. Given its promising activity, eravacycline may represent a member of the tetracycline class in treating cIAIs caused by commonly encountered Gram-negative and Gram-positive pathogens.

11.
Nano Lett ; 24(29): 8979-8987, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38994924

RESUMO

With the development of miniaturized devices, there is an increasing demand for 2D multifunctional materials. Six ferroelastic semiconductors, Y2Se2XX' (X, X' = I, Br, Cl, or F; X ≠ X') monolayers, are theoretically predicted here. Their in-plane anisotropic band structure, elastic and piezoelectric properties can be switched by ferroelastic strain. Moderate energy barriers can prevent the undesired ferroelastic switching that minor interferences produce. These monolayers exhibit high carrier mobilities (up to 104 cm2 V-1 s-1) with strong in-plane anisotropy. Furthermore, their wide bandgaps and high potential differences make them broad-pH-value and high-performance photocatalysts at pH value of 0-14. Strikingly, Y2Se2BrF possesses outstanding d33 (d33 = -405.97 pm/V), greatly outperforming CuInP2S6 by 4.26 times. Overall, the nano Y2Se2BrF is a hopeful candidate for multifunctional devices to generate a direct current and achieve solar-free photocatalysis. This work provides a new paradigm for the design of multifunctional energy materials.

12.
bioRxiv ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39026731

RESUMO

The circulation of seasonal influenza A viruses (IAVs) in humans relies on effective evasion and subversion of the host immune response. While the evolution of seasonal H1N1 and H3N2 viruses to avoid humoral immunity is well characterized, relatively little is known about the evolution of innate immune antagonism phenotypes in these viruses. Numerous studies have established that only a small subset of infected cells is responsible for initiating the type I and type III interferon (IFN) response during IAV infection, emphasizing the importance of single cell studies to accurately characterize the IFN response during infection. We developed a flow cytometry-based method to examine transcriptional changes in IFN and interferon stimulated gene (ISG) expression at the single cell level. We observed that NS segments derived from seasonal H3N2 viruses are more efficient at antagonizing IFN signaling but less effective at suppressing IFN induction, compared to the pdm2009 H1N1 lineage. We compared a collection of NS segments spanning the natural history of the current seasonal IAV lineages and demonstrate long periods of stability in IFN antagonism potential, punctuated by occasional phenotypic shifts. Altogether, our data reveal significant differences in how seasonal and pandemic H1N1 and H3N2 viruses antagonize the human IFN response at the single cell level.

13.
Langmuir ; 40(31): 16605-16614, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39039962

RESUMO

Despite its significant potential in various disease treatments and diagnostics, microbiotherapy is consistently plagued by multiple limitations ranging from manufacturing challenges to in vivo functionality. Inspired by the strategy involving nonproliferating yet metabolically active microorganisms, we report an intracellular gelation approach that can generate a synthetic polymer network within bacterial cells to solve these challenges. Specifically, poly(ethylene glycol dimethacrylate) (PEGDA, 700 Da) monomers are introduced into the bacterial cytosol through a single cycle of freeze-thawing followed by the initiation of intracellular free radical polymerization by UV light to create a macromolecular PEGDA gel within the bacterial cytosol. The molecular crowding resulting from intracytoplasmic gelation prohibits bacterial division and confers robust resistance to simulated gastrointestinal fluids and bile acids while retaining the ability to secrete functional proteins. Biocompatibility assessments demonstrate that the nondividing gelatinized bacteria are effective in alleviating systemic inflammation triggered by intravenous Escherichia coli injection. Furthermore, the therapeutic efficacy of gelatinized Lactobacillus rhamnosus in colitis mice provides additional support for this approach. Collectively, intracellular gelation indicates a universal strategy to manufacture next-generation live biotherapeutics for advanced microbiotherapy.


Assuntos
Escherichia coli , Polietilenoglicóis , Animais , Camundongos , Escherichia coli/efeitos dos fármacos , Polietilenoglicóis/química , Géis/química , Modelos Animais de Doenças , Colite/tratamento farmacológico , Colite/induzido quimicamente , Metacrilatos/química
14.
Rev Cardiovasc Med ; 25(5): 183, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-39076489

RESUMO

Background: Pulmonary artery catheters (PAC) are widely used in patients undergoing off-pump coronary artery bypass (OPCAB) grafting surgery. However, primary data suggested that the benefits of PAC in surgical settings were limited. Therefore, the present study sought to estimate the effects of PAC on the short-term outcomes of patients undergoing OPCAB surgery. Methods: The characteristics, intraoperative data, and postoperative outcomes of consecutive patients undergoing primary, isolated OPCAB surgery from November 2020 to December 2021 were retrospectively extracted. Patients were divided into two groups (PAC and no-PAC) based on PAC insertion status. Data were analyzed with a 1:1 nearest-neighbor propensity score matched-pair in PAC and no-PAC groups. Results: Of the 1004 Chinese patients who underwent primary, isolated OPCAB surgery, 506 (50.39%) had PAC. Propensity score matching yielded 397 evenly balanced pairs. Compared with the no-PAC group (only implanted a central venous catheter), PAC utilization was not associated with improved in-hospital mortality in the entire or matched cohort. Still, the matched cohort showed that PAC utilization increased epinephrine usage and hospital costs. Conclusions: The current study demonstrated no apparent benefit or harm for PAC utilization in OPCAB surgical patients. In addition, PAC utilization was more expensive.

15.
Int J Endocrinol ; 2024: 5588104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39040973

RESUMO

Introduction: The correlation between potassium and nonalcoholic fatty liver disease (NAFLD) is currently still poorly understood. We conducted this study to explore the correlation between dietary potassium intake and NAFLD, as well as advanced hepatic fibrosis (AHF). The study also sought to identify any potential interactions. Methods: The data employed in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) program, encompassing a period from 2007 to 2018. Employing the multiple logistic regression analysis, we evaluated the association of dietary potassium intake with NAFLD and AHF. Subsequently, stratification analysis, based on demographic variables, was constructed so as to assess the stability of the results. In addition, potential interaction effects were assessed by interaction tests. Results: A total of 9443 participants were included in the analysis. The mean age of the participants was 50.4 years, and their daily mean dietary potassium and vitamin C intake was 2556.49 mg and 82.93 mg, respectively. Following comprehensive statistical analyses, the findings indicated a negative correlation between dietary potassium intake and both NAFLD and AHF. Participants in Q4 group with dietary potassium intake exhibited a 31% and 42% reduction in the odds of developing NAFLD and AHF, respectively, in comparison to Q1 group. An interaction effect of dietary vitamin C intake was observed in the association between dietary potassium intake and NAFLD. The results imply that high dietary vitamin C intake augment the inverse relationship between dietary potassium intake and NAFLD. Conclusion: Dietary potassium intake was found to have an inverse association with the odds of both NAFLD and AHF. The association between dietary potassium intake and NAFLD was amplified by the presence of vitamin C in the diet.

16.
BMC Cancer ; 24(1): 714, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858644

RESUMO

BACKGROUND: Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). METHODS: Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. RESULTS: MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01-1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. CONCLUSION: RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.


Assuntos
Artrite Reumatoide , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Análise da Randomização Mendeliana , Miosinas/genética , Perfilação da Expressão Gênica , Transcriptoma , Locos de Características Quantitativas , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Multiômica
17.
Front Immunol ; 15: 1404108, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873601

RESUMO

Background: Forest musk deer (FMD, Moschus Berezovskii) is a critically endangered species world-widely, the death of which can be caused by pulmonary disease in the farm. Pulmonary fibrosis (PF) was a huge threat to the health and survival of captive FMD. MicroRNAs (miRNAs) and messenger RNAs (mRNAs) have been involved in the regulation of immune genes and disease development. However, the regulatory profiles of mRNAs and miRNAs involved in immune regulation of FMD are unclear. Methods: In this study, mRNA-seq and miRNA-seq in blood were performed to constructed coexpression regulatory networks between PF and healthy groups of FMD. The hub immune- and apoptosis-related genes in the PF blood of FMD were explored through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Further, protein-protein interaction (PPI) network of immune-associated and apoptosis-associated key signaling pathways were constructed based on mRNA-miRNA in the PF blood of the FMD. Immune hub DEGs and immune hub DEmiRNAs were selected for experimental verification using RT-qPCR. Results: A total of 2744 differentially expressed genes (DEGs) and 356 differentially expressed miRNAs (DEmiRNAs) were identified in the PF blood group compared to the healthy blood group. Among them, 42 DEmiRNAs were negatively correlated with 20 immune DEGs from a total of 57 correlations. The DEGs were significantly associated with pathways related to CD molecules, immune disease, immune system, cytokine receptors, T cell receptor signaling pathway, Th1 and Th2 cell differentiation, cytokine-cytokine receptor interaction, intestinal immune network for IgA production, and NOD-like receptor signaling pathway. There were 240 immune-related DEGs, in which 186 immune-related DEGs were up-regulated and 54 immune-related DEGs were down-regulated. In the protein-protein interaction (PPI) analysis of immune-related signaling pathway, TYK2, TLR2, TLR4, IL18, CSF1, CXCL13, LCK, ITGB2, PIK3CB, HCK, CD40, CD86, CCL3, CCR7, IL2RA, TLR3, and IL4R were identified as the hub immune genes. The mRNA-miRNA coregulation analysis showed that let-7d, miR-324-3p, miR-760, miR-185, miR-149, miR-149-5p, and miR-1842-5p are key miRNAs that target DEGs involved in immune disease, immune system and immunoregulation. Conclusion: The development and occurrence of PF were significantly influenced by the immune-related and apoptosis-related genes present in PF blood. mRNAs and miRNAs associated with the development and occurrence of PF in the FMD.


Assuntos
Cervos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs , Fibrose Pulmonar , RNA Mensageiro , Transcriptoma , Animais , MicroRNAs/genética , Cervos/genética , Cervos/imunologia , RNA Mensageiro/genética , Fibrose Pulmonar/genética , Fibrose Pulmonar/imunologia , Mapas de Interação de Proteínas , Regulação da Expressão Gênica , Biologia Computacional/métodos
19.
Pestic Biochem Physiol ; 202: 105936, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879328

RESUMO

The fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), is one of the most destructive agricultural pests. The entomopathogenic fungus Beauveria bassiana (Hypocreales: Clavicipitaceae) is a biopesticide widely used for biocontrol of various pests. Secreted fungal proteases are critical for insect cuticle destruction and successful infection. We have previously shown that the serine protease BbAorsin in B. bassiana has entomopathogenic and antiphytopathogenic activities. However, the contribution of BbAorsin to fungal growth, conidiation, germination, virulence and antiphytopathogenic activities remains unclear. In this study, the deletion (ΔBbAorsin), complementation (Comp), and overexpression (BbAorsinOE) strains of B. bassiana were generated for comparative studies. The results showed that ΔBbAorsin exhibited slower growth, reduced conidiation, lower germination rate, and longer germination time compared to WT and Comp. In contrast, BbAorsinOE showed higher growth rate, increased conidiation, higher germination rate and shorter germination time. Injection of BbAorsinOE showed the highest virulence against S. frugiperda larvae, while injection of ΔBbAorsin showed the lowest virulence. Feeding BbAorsinOE resulted in lower pupation and adult eclosion rates and malformed adults. 16S rRNA sequencing revealed no changes in the gut microbiota after feeding either WT or BbAorsinOE. However, BbAorsinOE caused a disrupted midgut, leakage of gut microbiota into the hemolymph, and upregulation of apoptosis and immunity-related genes. BbAorsin can disrupt the cell wall of the phytopathogen Fusarium graminearum and alleviate symptoms in wheat seedlings and cherry tomatoes infected with F. graminearum. These results highlight the importance of BbAorsin for B. bassiana and its potential as a multifunctional biopesticide.


Assuntos
Beauveria , Beauveria/patogenicidade , Beauveria/genética , Beauveria/fisiologia , Animais , Virulência , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Spodoptera/microbiologia , Esporos Fúngicos , Larva/microbiologia , Serina Proteases/metabolismo , Serina Proteases/genética , Controle Biológico de Vetores , Fusarium/patogenicidade , Fusarium/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-38809724

RESUMO

This scoping review paper redefines the Artificial Intelligence-based Internet of Things (AIoT) driven Human Activity Recognition (HAR) field by systematically extrapolating from various application domains to deduce potential techniques and algorithms. We distill a general model with adaptive learning and optimization mechanisms by conducting a detailed analysis of human activity types and utilizing contact or non-contact devices. It presents various system integration mathematical paradigms driven by multimodal data fusion, covering predictions of complex behaviors and redefining valuable methods, devices, and systems for HAR. Additionally, this paper establishes benchmarks for behavior recognition across different application requirements, from simple localized actions to group activities. It summarizes open research directions, including data diversity and volume, computational limitations, interoperability, real-time recognition, data security, and privacy concerns. Finally, we aim to serve as a comprehensive and foundational resource for researchers delving into the complex and burgeoning realm of AIoT-enhanced HAR, providing insights and guidance for future innovations and developments.

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