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1.
BMC Infect Dis ; 24(1): 240, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389047

RESUMO

OBJECTIVE: This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. METHODS: Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. RESULTS: SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P < 0.05). Multivariate analysis identified elevated LDH upon admission (OR = 1.004, 95% CI: 1-1.008, P = 0.050), elevated NT-proBNP (OR = 1.005, 95% CI: 1.001-1.008, P = 0.007), and consciousness disorders (OR = 112.852, 95% CI: 3.676 ~ 3464.292, P = 0.007) as independent risk factors for SFTS-SVM. LDH and NT-proBNP had AUCs of 0.728 and 0.744, respectively, in predicting SFTS-SVM. Critical values of LDH (> 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. CONCLUSION: Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds.


Assuntos
Miocardite , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Trombocitopenia , Viroses , Humanos , Estudos Retrospectivos , Trombocitopenia/complicações , Trombocitopenia/diagnóstico , Miocardite/complicações , Miocardite/diagnóstico , Transtornos da Consciência/complicações , Febre/complicações
2.
BMC Infect Dis ; 24(1): 1210, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39468445

RESUMO

BACKGROUND: Information on the comparison of blood microbiota between human immunodeficiency virus (HIV)-infected and HIV-uninfected patients with suspected sepsis by metagenomic next-generation sequencing (mNGS) is limited. METHODS: Retrospectively analysis was conducted in HIV-infected and HIV-uninfected patients with suspected sepsis at Changsha First Hospital (China) from March 2019 to August 2022. Patients who underwent blood mNGS testing were enrolled. The blood microbiota detected by mNGS were analyzed. RESULTS: A total of 233 patients with suspected sepsis who performed blood mNGS were recruited in this study, including 79 HIV-infected and 154 HIV-uninfected patients. Compared with HIV-uninfected patients, the proportions of mycobacterium (p = 0.001), fungus (p < 0.001) and viruses (p < 0.001) were significantly higher, while the proportion of bacteria (p = 0.001) was significantly lower in HIV-infected patients. The higher positive rates of non-tuberculous mycobacteriosis (NTM, p = 0.022), Pneumocystis jirovecii (P. jirovecii) (p = 0.014), Talaromyces marneffei (T. marneffei) (p < 0.001) and cytomegalovirus (CMV) (p < 0.001) were observed in HIV-infected patients, compared with HIV-uninfected patients. In addition, compared with HIV-uninfected patients, the constituent ratio of T. marneffei (p < 0.001) in the fungus spectrum were significantly higher, while the constituent ratios of Candida (p < 0.001) and Aspergillus (p = 0.001) were significantly lower in HIV-infected patients. CONCLUSIONS: Significant differences in the blood microbiota profiles exist between HIV-infected and HIV-uninfected patients with suspected sepsis.


Assuntos
Infecções por HIV , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Microbiota , Sepse , Humanos , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Sepse/microbiologia , Sepse/sangue , Estudos Retrospectivos , Adulto , Metagenômica/métodos , China , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Idoso
3.
Environ Res ; 250: 118470, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38373548

RESUMO

In-situ passivation technique has attracted increasing attention for metal-contaminated agricultural soil remediation. However, metal immobilization mechanisms are mostly illustrated based on metal speciation changes and alterations in soil physicochemical properties from a macroscopic and abiotic perspective. In this study, a ferrihydrite-synthetic humic-like acid composite (FH-SHLA) was fabricated and applied as a passivator for a 90-day soil incubation. The heavy metals immobilization mechanisms of FH-SHLA were investigated by combining both abiotic and biotic perspectives. Effects of FH-SHLA application on soil micro-ecology were also evaluated. The results showed that the 5%FH-SHLA treatment significantly decreased the DTPA-extractable Pb, Cd and Zn by 80.75%, 46.82% and 63.63% after 90 days of incubation (P < 0.05), respectively. Besides, 5% FH-SHLA addition significantly increased soil pH, soil organic matter content and cation exchange capacity (P < 0.05). The SEM, FTIR, and XPS characterizations revealed that the abiotic metal immobilization mechanisms by FH-SHLA included surface complexation, precipitation, electrostatic attraction, and cation-π interactions. For biotic perspective, in-situ microorganisms synergistically participated in the immobilization process via sulfide precipitation and Fe mineral production. FH-SHLA significantly altered the diversity and composition of the soil microbial community, and enhanced the intensity and complexity of the microbial co-occurrence network. Both metal bioavailability and soil physiochemical parameters played a vital role in shaping microbial communities, while the former contributed more. Overall, this study provides new insight into the heavy metal passivation mechanism and demonstrates that FH-SHLA is a promising and environmentally friendly amendment for metal-contaminated soil remediation.


Assuntos
Compostos Férricos , Substâncias Húmicas , Metais Pesados , Poluentes do Solo , Solo , Poluentes do Solo/análise , Poluentes do Solo/química , Substâncias Húmicas/análise , Compostos Férricos/química , Solo/química , Metais Pesados/análise , Microbiologia do Solo , Recuperação e Remediação Ambiental/métodos , Agricultura/métodos
4.
Cell Commun Signal ; 21(1): 327, 2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974196

RESUMO

Regulated cell death (RCD) is a regulable cell death that involves well-organized signaling cascades and molecular mechanisms. RCD is implicated in fundamental processes such as organ production and tissue remodeling, removing superfluous structures or cells, and regulating cell numbers. Previous studies have not been able to reveal the complete mechanisms, and novel methods of RCD are constantly being proposed. Two metal ions, iron (Fe) and copper (Cu) are essential factors leading to RCDs that not only induce ferroptosis and cuproptosis, respectively but also lead to cell impairment and eventually diverse cell death. This review summarizes the direct and indirect mechanisms by which Fe and Cu impede cell growth and the various forms of RCD mediated by these two metals. Moreover, we aimed to delineate the interrelationships between these RCDs with the distinct pathways of ferroptosis and cuproptosis, shedding light on the complex and intricate mechanisms that govern cellular survival and death. Finally, the prospects outlined in this review suggest a novel approach for investigating cell death, which may involve integrating current therapeutic strategies and offer a promising solution to overcome drug resistance in certain diseases. Video Abstract.


Assuntos
Ferroptose , Morte Celular Regulada , Morte Celular , Cobre , Ferro , Apoptose
5.
Environ Res ; 232: 116309, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37301498

RESUMO

Polychlorinated naphthalenes (PCNs) have stopped being produced and used but have been detected in human serum around the world. Investigating temporal trends in PCN concentrations in human serum will improve our understanding of human exposure to PCNs and the risks posed. We determined the PCN concentrations in serum collected from 32 adults in five consecutive years (2012-2016). The total PCN concentrations in the serum samples were 0.00-5443 pg/g lipid weight. We found no significant decreases in the total PCN concentrations in human serum and even found that the concentrations of some PCN congeners (e.g., CN20) increased over time. We found differences in the PCN concentrations in serum from males and females, the CN75 concentration being significantly higher in serum from females than males, meaning CN75 poses more serious risks to females than males. We found, using molecular docking techniques, that CN75 interferes with thyroid hormone transport in vivo and that CN20 affects thyroid hormone binding to receptors. These two effects are synergistic and can cause hypothyroidism-like symptoms.


Assuntos
População do Leste Asiático , Naftalenos , Glândula Tireoide , Adulto , Feminino , Humanos , Masculino , Monitoramento Ambiental , Simulação de Acoplamento Molecular , Naftalenos/sangue , Naftalenos/toxicidade , Glândula Tireoide/efeitos dos fármacos
6.
Cancer Cell Int ; 22(1): 230, 2022 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-35843949

RESUMO

BACKGROUND: The critical role of thioredoxin-interacting protein (TXNIP) in cellular sulfhydryl redox homeostasis and inflammasome activation is already widely known, however, no pan-cancer analysis is currently available. METHODS: We thus first explored the potential roles of TXNIP across thirty-three tumors mainly based on The Cancer Genome Atlas and Gene Expression Omnibus datasets. RESULTS: TXNIP is lowly expressed in most cancers, and distinct associations exist between TXNIP expression and the prognosis of tumor patients. TXNIP expression was associated with tumor mutational burden, microsatellite instability, mismatch repair genes, tumor infiltrating immune cell abundance as well as cancer-associated fibroblasts. Moreover, ubiquitin mediated proteolysis, protein post-translational modification and other related pathways were involved in the functional mechanisms of TXNIP. CONCLUSIONS: Our first pan-cancer study comprehensively revealed the carcinostatic role of TXNIP across different tumors. And this molecule may be considered as a potential immunological and prognostic biomarker.

7.
Neurochem Res ; 47(11): 3355-3368, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35962937

RESUMO

Protein glycosylation plays a crucial role in central nervous system, and abnormal glycosylation has major implications for human diseases. This study aims to evaluate an etiological implication of the variation in glycosylation for Parkinson's disease (PD), a neurodegenerative disorder. Based on a PD mouse model constructed by the intraperitoneal injection with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, glycosylation variation was accessed using biotinylated lectin of dolichos biflorus agglutinin (DBA) specific for the exposed N-acetylgalactosamine linked to glycoprotein. Consequently, a glycoprotein with a significantly reduced N-acetylgalactosamination was identified as ADP/ATP translocase 1 (ANT1) by lectin affinity chromatography coupled with MALDI-TOF MS/MS (mass spectrometry), and confirmed by the analysis of dual co-immunofluorescence and Western blot. A tissue-specific distribution of de-N-acetylgalactosaminated ANT1 was found to be correlated with high risk of PD. At cellular level, an obvious co-aggregation between ANT1 and DBA was only found in the MPP+-induced PD-like cell model using dual co-immunofluorescence. Thus, we found that ANT1 was a potential glycoprotein with terminal N-acetylgalactosamine moiety, and the variation of glycosylation in ANT1 was associated with PD. This investigation provides an innovative insight in protein glycosylation with PD pathogenesis.


Assuntos
Doença de Parkinson , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Acetilgalactosamina , Translocador 1 do Nucleotídeo Adenina , Difosfato de Adenosina/metabolismo , Animais , Glicoproteínas/metabolismo , Camundongos , Translocases Mitocondriais de ADP e ATP/metabolismo , Doença de Parkinson/metabolismo , Espectrometria de Massas em Tandem
8.
J Biol Chem ; 294(14): 5438-5455, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30745361

RESUMO

Asthma is a common inflammatory pulmonary disorder involving a diverse array of immune cells such as proinflammatory T helper 2 (Th2) cells. We recently reported that intraperitoneal injection of α-galactosylceramide (α-GalCer) can stimulate the lung invariant natural killer T (iNKT) cells and does not lead to airway inflammation in WT mice. Other studies indicate that iNKT cells play an important role in inducing regulatory T cells (Treg cells) and peripheral tolerance. Using iNKT cell- knockout mice, functional inactivation of Treg cells, and co-culture experiments in murine asthma models, we investigated the immunoregulatory effects of α-GalCer treatment before allergen sensitization on Th2 cell responses. We also studied whether α-GalCer's effects require lung Treg cells induced by activated iNKT cells. Our results disclosed that intraperitoneal administration of α-GalCer before allergen sensitization could promote the expansion and suppressive activity of lung CD4+FoxP3+ Treg cells. These effects were accompanied by down-regulated Th2 cell responses and decreased immunogenic maturation of lung dendritic cells in WT mice. However, these changes were absent in CD1d-/- mice immunized and challenged with ovalbumin or house dust mites, indicating that the effects of α-GalCer on Treg cells mainly require iNKT cells. Moreover, functional inactivation of Treg cells could reverse the inhibitory ability of this α-GalCer therapy on Th2 cell responses in a murine asthma model. Our findings indicate that intraperitoneal administration of α-GalCer before the development of asthma symptoms induces the generation of lung Treg cells via iNKT cells and may provide a potential therapeutic strategy to prevent allergic asthma.


Assuntos
Alérgenos/toxicidade , Asma/prevenção & controle , Galactosilceramidas/farmacologia , Células T Matadoras Naturais/imunologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Alérgenos/imunologia , Animais , Asma/induzido quimicamente , Asma/imunologia , Asma/patologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Células T Matadoras Naturais/patologia , Pyroglyphidae/imunologia , Linfócitos T Reguladores/patologia , Células Th2/patologia
9.
J Cell Mol Med ; 23(2): 1072-1085, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30421497

RESUMO

Our previous study showed that intraperitoneal injection of α-galactosylceramide (α-GalCer) has the ability to activate lung iNKT cells, but α-GalCer-activated iNKT cells do not result in airway inflammation in wild-type (WT) mice. Many studies showed that iNKT cells had the capacity to induce Treg cells, which gave rise to peripheral tolerance. Therefore, we examined the influence of intraperitoneal administration of α-GalCer on the expansion and suppressive activity of lung Treg cells using iNKT cell-knockout mice and co-culture experiments in vitro. We also compared airway inflammation and airway hyperresponsiveness (AHR) after α-GalCer administration in specific anti-CD25 mAb-treated mice. Our data showed that intraperitoneal injection of α-GalCer could promote the expansion of lung Treg cells in WT mice, but not in iNKT cell-knockout mice. However, α-GalCer administration could not boost suppressive activity of Treg cells in WT mice and iNKT cell-knockout mice. Interestingly, functional inactivation of Treg cells could induce airway inflammation and AHR in WT mice treated with α-GalCer. Furthermore, α-GalCer administration could enhance iNKT cells to secrete IL-2, and neutralization of IL-2 reduced the expansion of Treg cells in vivo and in vitro. Thus, intraperitoneal administration of α-GalCer can induce the generation of lung Treg cells in mice through the release of IL-2 by the activated iNKT cells.


Assuntos
Galactosilceramidas/imunologia , Células T Matadoras Naturais/imunologia , Linfócitos T Reguladores/imunologia , Animais , Feminino , Interleucina-2/imunologia , Pulmão/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
10.
Genes (Basel) ; 15(5)2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38790173

RESUMO

Alternanthera sessilis is considered the closest relative to the invasive weed Alternanthera philoxeroides in China, making it an important native species for studying the invasive mechanisms and adaptations of A. philoxeroides. Chloroplasts play a crucial role in a plant's environmental adaptation, with their genomes being pivotal in the evolution and adaptation of both invasive and related species. However, the chloroplast genome of A. sessilis has remained unknown until now. In this study, we sequenced and assembled the complete chloroplast genome of A. sessilis using high-throughput sequencing. The A. sessilis chloroplast genome is 151,935 base pairs long, comprising two inverted repeat regions, a large single copy region, and a small single copy region. This chloroplast genome contains 128 genes, including 8 rRNA-coding genes, 37 tRNA-coding genes, 4 pseudogenes, and 83 protein-coding genes. When compared to the chloroplast genome of the invasive weed A. philoxeroides and other Amaranthaceae species, we observed significant variations in the ccsA, ycf1, and ycf2 regions in the A. sessilis chloroplast genome. Moreover, two genes, ccsA and accD, were found to be undergoing rapid evolution due to positive selection pressure. The phylogenetic trees were constructed for the Amaranthaceae family, estimating the time of independent species formation between A. philoxeroides and A. sessilis to be approximately 3.5186-8.8242 million years ago. These findings provide a foundation for understanding the population variation within invasive species among the Alternanthera genus.


Assuntos
Amaranthaceae , Genoma de Cloroplastos , Espécies Introduzidas , Filogenia , Genoma de Cloroplastos/genética , Amaranthaceae/genética , Plantas Daninhas/genética , Cloroplastos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Evolução Molecular
11.
Front Genet ; 15: 1392110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784042

RESUMO

In this study, we investigate gynogenetic reproduction in Pengze Crucian Carp (Carassius auratus var. pengsenensis) using third-generation Nanopore sequencing to uncover structural variations (SVs) in offspring. Our objective was to understand the role of male genetic material in gynogenesis by examining the genomes of both parents and their offspring. We discovered a notable number of male-specific structural variations (MSSVs): 1,195 to 1,709 MSSVs in homologous offspring, accounting for approximately 0.52%-0.60% of their detected SVs, and 236 to 350 MSSVs in heterologous offspring, making up about 0.10%-0.13%. These results highlight the significant influence of male genetic material on the genetic composition of offspring, particularly in homologous pairs, challenging the traditional view of asexual reproduction. The gene annotation of MSSVs revealed their presence in critical gene regions, indicating potential functional impacts. Specifically, we found 5 MSSVs in the exonic regions of protein-coding genes in homologous offspring, suggesting possible direct effects on protein structure and function. Validation of an MSSV in the exonic region of the polyunsaturated fatty acid 5-lipoxygenase gene confirmed male genetic material transmission in some offspring. This study underscores the importance of further research on the genetic diversity and gynogenesis mechanisms, providing valuable insights for reproductive biology, aquaculture, and fostering innovation in biological research and aquaculture practices.

12.
Front Microbiol ; 15: 1421660, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39372273

RESUMO

Introduction: This study aimed to assess the diagnostic values of bronchoalveolar lavage fluid (BALF) real-time polymerase chain reaction (PCR) and BALF metagenomic next-generation sequencing (mNGS) for Pneumocystis jirovecii pneumonia (PJP) in patients infected with human immunodeficiency virus (HIV). Methods: A total of 99 HIV-infected PJP patients and 61 HIV-infected patients diagnosed with non-PJP pneumonia between March 2019 and December 2022 were enrolled. P. jirovecii and multiple other co-pathogens detected in BALF by mNGS were analyzed. The clinical final diagnosis was employed as a benchmark. We compared the diagnostic performance of mNGS in PJP with serum BDG and BALF real-time PCR. The mixed infections detected by mNGS and modifications of antimicrobial treatment were also analyzed. Results: The sensitivity of mNGS test of BALF samples reached 85.86%, which was significantly higher than serum BDG (39.39%, P < 0.001). The sensitivity of BALF P. jirovecii PCR (84.85%) was similar with mNGS (P > 0.05). The specificity of mNGS (100%) was also same as PCR (100.0%), and superior to serum BDG (88.52%, P < 0.001). Besides, mNGS performs remarkably well in identifying co-pathogens of PJP patients infected with HIV. In addition to P. jirovecii, 82 cases (82.83%) of other co-pathogens were identified based on mNGS. Moreover, thirty-four patients (34.34%) increased therapeutic dose of trimethoprim-sulfamethoxazole (TMP-SMZ) based on BALF P. jirovecii PCR. Based on the mNGS results, initial antimicrobial treatment was modified in 86.87% (86/99) of PJP patients. Conclusion: BALF mNGS and real-time PCR are two powerful techniques for rapid diagnosis of PJP with high specificity and sensitivity. Moreover, the benefit of mNGS is that it may identify other organisms besides PJP and it may benefit proper and prompt treatment.

13.
Int J Biol Macromol ; 263(Pt 2): 130347, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401583

RESUMO

Polypeptide N-acetylgalactosamine transferase 9 (GALNT9) catalyzes the initial step of mucin-type O-glycosylation via linking N-acetylgalactosamine (GalNAc) to serine/threonine in a protein. To unravel the association of GALNT9 with Parkinson's disease (PD), a progressive neurodegenerative disorder, GALNT9 levels were evaluated in the patients with PD and mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and statistically analyzed based on the GEO datasets of GSE114918 and GSE216281. Glycoproteins with exposing GalNAc were purified using lectin affinity chromatography and identified by LC-MS/MS. The influence of GALNT9 on cells was evaluated via introducing a GALNT9-specific siRNA into SH-SY5Y cells. Consequently, GALNT9 deficiency was found to occur under PD conditions. GALNT9 silencing contributed to a causative factor in PD pathogenesis via reducing the levels of intracellular dopamine, tyrosine hydroxylase and soluble α-synuclein, and promoting α-synuclein aggregates. MS identification revealed 14 glycoproteins. 5 glycoproteins, including ACO2, ATP5B, CKB, CKMT1A, ALDOC, were associated with energy metabolism. GALNT9 silencing resulted in mitochondrial dysfunctions via increasing ROS accumulation, mitochondrial membrane depolarization, mPTPs opening, Ca2+ releasing and activation of the CytC-related apoptotic pathway. The dysfunctional mitochondria then triggered mitophagy, possibly intermediated by adenine nucleotide translocase 1. Our study suggests that GALNT9 is potentially developed into an auxiliary diagnostic index and therapeutic target of PD.


Assuntos
Doenças Mitocondriais , N-Acetilgalactosaminiltransferases , Neuroblastoma , Doença de Parkinson , Humanos , Camundongos , Animais , Doença de Parkinson/metabolismo , alfa-Sinucleína/química , Acetilgalactosamina/química , Transferases , Cromatografia Líquida , Espectrometria de Massas em Tandem , Peptídeos , Glicoproteínas , N-Acetilgalactosaminiltransferases/genética , N-Acetilgalactosaminiltransferases/metabolismo , Creatina Quinase
14.
Mol Clin Oncol ; 20(3): 25, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38410186

RESUMO

Ailanthone (AIL), a monomer derived from ailanthus in Chinese medicine, has been demonstrated to have antitumor effects, albeit the underlying mechanism is unknown. Autophagy and ferroptosis are two modes of cell death that have been championed as potential mechanisms implicated in the antitumor effects of various drugs. The present study demonstrated that AIL effectively suppresses the Lewis cell proliferation in non-small cell lung cancer using MTT and colony formation assays. Autophagy and ferroptosis were verified using western blotting, immunofluorescence and ferroptosis detection. Additionally, the findings revealed that regulating the AMPK/mTOR/p70S6k signaling pathway may be the underlying mechanism for the antitumor effect of AIL. The present study established a theoretical foundation for further research into the utilization of AIL as a novel antitumor approach.

15.
Chemosphere ; 352: 141380, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38368958

RESUMO

Polybrominated diphenyl ethers (PBDEs) have been detected in various environmental media and human tissues. PBDEs concentrations in dust from college buildings and homes and in paired hair and urine samples from students were determined. This is of great significance to explore the accumulation and excretion patterns of PBDEs in the human body. The median PBDEs concentrations in the dust (College: 84.59 ng/g; Home: 170.32 ng/g) and hair (undergraduate: 6.16 ng/g; Home: 3.25 ng/g) samples were generally lower than were found in the majority of previous studies. The PBDEs concentrations in the hair and urine samples were subjected to principal component analysis, and the results combined with the PBDEs detection rates confirmed that hair is a useful non-invasive sampling medium for assessing PBDEs exposure and the risks posed. Body mass indices (BMIs) were used to divide students who had not been exposed to large amounts of PBDEs into groups. Body fat percentage is an important factor affecting the accumulation of PBDE in the human body. Environmental factors were found to affect the PBDEs concentrations in the hair and urine samples less for normal-weight students (BMI≤24) than overweight students (BMI>24). Short-term environmental changes to more readily affect the PBDEs concentrations in the tissues of the normal-weight than overweight students. PBDEs with seven or more bromine substituents were found not to be readily excreted in urine. Performing molecular docking simulations of the binding of isomers BDE-99 and BDE-100 to megalin. The binding energy was higher for BDE-100 and megalin than for BDE-99 and megalin, meaning BDE-99 would be more readily excreted than BDE-100.


Assuntos
Monitoramento Ambiental , Éteres Difenil Halogenados , Bifenil Polibromatos , Humanos , Monitoramento Ambiental/métodos , Éteres Difenil Halogenados/análise , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/análise , Poeira/análise , Simulação de Acoplamento Molecular , Sobrepeso , Cabelo/química , Exposição Ambiental/análise
16.
Oncol Res ; 32(4): 643-658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560570

RESUMO

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma (LUAD), and chemoresistance, however, usually results in treatment failure and limits its application in the clinic. It has been shown that microRNAs (miRNAs) play a significant role in tumor chemoresistance. In this study, miR-125b was identified as a specific cisplatin (DDP)-resistant gene in LUAD, as indicated by the bioinformatics analysis and the real-time quantitative PCR assay. The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time. MiR-125b decreased the A549/DDP proliferation, and the multiple drug resistance- and autophagy-related protein expression levels, which were all reversed by the inhibition of miR-125b. In addition, xenografts of human tumors in nude mice were suppressed by miR-125b, demonstrating that through autophagy regulation, miR-125b could reverse the DDP resistance in LUAD cells, both in vitro and in vivo. Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L, which in turn inhibited autophagy and reversed chemoresistance. Based on these findings, miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , Proteínas Supressoras de Tumor , Animais , Camundongos , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos Nus , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Apoptose/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Autofagia/genética , Regulação Neoplásica da Expressão Gênica , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/farmacologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/genética
17.
Biomark Res ; 12(1): 29, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419056

RESUMO

Colorectal cancer (CRC) is a common malignancy worldwide. Angiogenesis and metastasis are the critical hallmarks of malignant tumor. Runt-related transcription factor 1 (RUNX1), an efficient transcription factor, facilitates CRC proliferation, metastasis and chemotherapy resistance. We aimed to investigate the RUNX1 mediated crosstalk between tumor cells and M2 polarized tumor associated macrophages (TAMs) in CRC, as well as its relationship with neoplastic angiogenesis. We found that RUNX1 recruited macrophages and induced M2 polarized TAMs in CRC by promoting the production of chemokine 2 (CCL2) and the activation of Hedgehog pathway. In addition, we found that the M2 macrophage-specific generated cytokine, platelet-derived growth factor (PDGF)-BB, promoted vessel formation both in vitro and vivo. PDGF-BB was also found to enhance the expression of RUNX1 in CRC cell lines, and promote its migration and invasion in vitro. A positive feedback loop of RUNX1 and PDGF-BB was thus formed. In conclusion, our data suggest that RUNX1 promotes CRC angiogenesis by regulating M2 macrophages during the complex crosstalk between tumor cells and TAMs. This observation provides a potential combined therapy strategy targeting RUNX1 and TAMs-related PDGF-BB in CRC.

18.
Insects ; 14(6)2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37367317

RESUMO

Agasicles hygrophila Selman and Vogt (Coleoptera: Chrysomelidae) is the key natural enemy of Alternanthera philoxeroides (Mart.) Griseb, an invasive weed worldwide. To understand the morphology of A. hygrophila and further explore the specific host localization mechanism, scanning electron microscopy was used to observe and study the morphological characteristics of sensilla on the head appendages, tarsi, and external genital segments of A. hygrophila. Twelve types and forty-six subtypes of sensilla were observed. These contain various types of head appendices, including sensilla chaetica, sensilla trichodea, sensilla basiconca, sensilla coeloconica, sensilla styloconica, Böhm bristles, sensilla campaniform, sensilla terminal, sensilla dome, sensilla digit-like, sensilla aperture, and many subtypes. A new type of sensor was reported for the first time, which may be related to host plant recognition. This sensor was located on the distal segment of the maxillary palps of A. hygrophila and was named as sensilla petal-shaped based on its morphological characteristics. Sensilla chaetica, sensilla trichodea, and sensilla basiconca are also found on the tarsi and external genital segments. In addition, sensilla basiconica 4, sensilla coeloconica 1 and 2, sensilla styloconica 2, Böhm bristles 2, and sensilla campaniform 1 were only found in females. On the contrary, sensilla styloconica 3, sensilla coeloconica 3, and sensilla dome were only found in males. Numbers and sizes of the sensilla were also different between males and females. The potential functions related to structure were discussed in comparison with previous investigations on beetles and other monophagous insects. Our results provide a microscopic morphological basis for further research on the localization and recognition mechanism of A. hygrophila and its obligate host.

19.
Shock ; 59(3): 368-374, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36562264

RESUMO

ABSTRACT: Objectives: We attempted to identify and validate the subphenotypes of sepsis-associated liver dysfunction (SALD) using routine clinical information. Design: This article is a retrospective observational cohort study. Setting: We used the Medical Information Mart for Intensive Care IV database and the eICU Collaborative Research Database. Patients: We included adult patients (age ≥18 years) who developed SALD within the first 48 hours of intensive care unit (ICU) admission. We excluded patients who died or were discharged from the ICU within the first 48 hours of admission. Patients with abnormal liver function before ICU admission were also excluded. Measurements and Main Results: Patients in the MIMIC-IV 1.0 database served as a derivation cohort. Patients in the eICU database were used as validation cohort. We identified four subphenotypes of SALD (subphenotype α, ß, γ, δ) using K-means cluster analysis in 5234 patients in derivation cohort. The baseline characteristics and clinical outcomes were compared between the phenotypes using one-way analysis of variance/Kruskal-Wallis test and the χ 2 test. Moreover, we used line charts to illustrate the trend of liver function parameters over 14 days after ICU admission. Subphenotype α (n = 1,055) was the most severe cluster, characterized by shock with multiple organ dysfunction (MODS) group. Subphenotype ß (n = 1,179) had the highest median bilirubin level and the highest proportion of patients with underlying liver disease and coexisting coagulopathy (increased bilirubin group). Subphenotype γ (n = 1,661) was the cluster with the highest mean age and had the highest proportion of patients with chronic kidney disease (aged group). Subphenotype δ (n = 1,683) had the lowest 28-day and in-hospital mortality (mild group). The characteristics of clusters in the validation cohort were similar to those in the derivation cohort. In addition, we were surprised to find that GGT levels in subphenotype δ were significantly higher than in other subphenotypes, showing a different pattern from bilirubin. Conclusions: We identified four subphenotypes of SALD that presented with different clinical features and outcomes. These results can provide a valuable reference for understanding the clinical characteristics and associated outcomes to improve the management of patients with SALD in the ICU.


Assuntos
Hepatopatias , Sepse , Humanos , Estudos Retrospectivos , Fenótipo , Análise por Conglomerados , Unidades de Terapia Intensiva
20.
Heart Lung ; 61: 72-83, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37167901

RESUMO

BACKGROUND: Anticoagulation is critical in patients supported on extracorporeal membrane oxygenation (ECMO). The appropriate monitoring strategies for heparin remain unclear. OBJECTIVES: This systematic review aimed to compare the accuracy and safety of various monitoring strategies for patients supported on ECMO. METHODS: The PubMed and Web of Science databases were searched for articles in March 2023 without restrictions on publication date. Anticoagulation monitoring strategies for adults supported on ECMO were compared across all included studies. The incidence of bleeding, thrombosis, mortality, blood transfusion, correlation between tests and heparin dose, and the discordance between different tests were discussed in the included studies. The risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane Collaboration's tool. RESULTS: Twenty-six studies, including a total of 1,684 patients, met the inclusion criteria. The monitoring of anticoagulation by activated partial thromboplastin time (aPTT) resulted in less blood product transfusion than that by activated clotting time (ACT). Moreover, the monitoring of anticoagulation by anti-factor Xa (Anti-Xa) resulted in a more stable anticoagulation than that by aPTT. Anti-Xa and aPTT correlated with heparin dose better than ACT, and the discordance between different monitoring tests was common. Finally, combined monitoring showed some advantages in reducing mortality and blood product transfusion. CONCLUSION: Anti-Xa and aPTT are more suitable for anticoagulation monitoring for patients supported on ECMO than ACT. Thromboelastography and combination strategies are less applied. Most of the studies were retrospective, and their sample sizes were relatively small; thus, more appropriate monitoring strategies and higher quality research are needed.


Assuntos
Anticoagulantes , Oxigenação por Membrana Extracorpórea , Humanos , Adulto , Anticoagulantes/uso terapêutico , Estudos Retrospectivos , Heparina/uso terapêutico , Tempo de Tromboplastina Parcial
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