Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 113
Filtrar
1.
Heliyon ; 10(11): e32036, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38882277

RESUMO

Bone regeneration plays a pivotal role in periodontal tissue repair. With advancements in biotechnology materials, the utilization of nanotechnology offers a reliable platform for bone restoration in periodontitis. In this study, we successfully established a long-term bacterial infection model using Porphyromonas gingivalis (P. gingivalis) with MOI = 50. CCK-8 and ROS immunofluorescence results demonstrated that the combined effect of Mg2+ and AS-IV significantly enhanced cell proliferation and effectively suppressed the inflammatory response during bacterial infection. Alkaline phosphatase and alizarin red staining revealed that the synergistic action of Mg2+ and AS-IV notably promoted osteogenic differentiation of MC3T3-E1 cells under P. gingivalis-infected conditions. Considering the properties of these two biomaterials, we fabricated polycaprolactone (PCL) artificial periosteum loaded with MgO and AS-IV using an electrostatic spinning technique. The findings indicated that PCL/MgO/AS-IV artificial periosteum exhibited excellent biocompatibility and hydrophilicity, thereby substantially enhancing cellular adhesion to its surface as well as augmenting cellular value-added rate. Moreover, efficient drug release from the PCL/MgO/AS-IV artificial bone membrane conferred remarkable antimicrobial activity along with in vitro osteogenic potentiality. The in vivo experiments conducted on animals further substantiated the exceptional properties exhibited by PCL/MgO/AS-IV artificial periosteum in bone defect repair. Additionally, it was observed that PCL/MgO/AS-IV artificial periosteum could modulate EphB4-EphrinB2 signaling to enhance osteogenic differentiation under P.gingivalis-infected conditions.This exciting outcome suggests that PCL/MgO/AS-IV artificial periosteum holds great promise as a biomaterial for treating periodontal bone loss.

2.
Genes Dis ; 11(4): 101114, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38560500

RESUMO

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic program. Phosphoenolpyruvate carboxylase 1 (PCK1), a gluconeogenic metabolic enzyme, is down-regulated in hepatocellular carcinoma and is closely related to poor prognosis. The oncogenesis and progression of tumors are closely related to cancer stem cells. It is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular carcinoma. Herein, the results showed that PCK1 inhibited the self-renewal property of hepatoma cells, reduced the mRNA level of cancer stem cell markers, and inhibited tumorigenesis. Moreover, PCK1 increased the sensitivity of hepatocellular carcinoma cells to sorafenib. Furthermore, we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear translocation. Verteporfin reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of sorafenib. Thus, combined treatment with verteporfin and sorafenib may be a potential anti-tumor strategy in hepatocellular carcinoma.

3.
Breast ; 75: 103735, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38640552

RESUMO

PURPOSE: To determine financial toxicity in young and middle-aged women with breast cancer and examine the associations between family resilience and negative emotions. METHODS: A multicentre cross-sectional study was conducted, 538 women with breast cancer were recruited from four hospitals. FT, family resilience, and negative emotions were collected using the Comprehensive Score for FT, the Chinese version of the Family Resilience Assessment in Breast Cancer Patients, Patient Health Questionnaire-9 item, and Generalized Anxiety Disorder-7. This study adhered to the STROBE guidelines. RESULTS: The valid response rate was 96.8 % (N = 521). Overall, the score for FT was 19.63 ± 10.13. FT was significantly correlated with family resilience (r = 0.30, p < 0.010) and depression (r = -0.11, p < 0.050). The hierarchical multiple linear regression analysis showed that career status, monthly income, religion, and family resilience were the main factors influencing FT in patients with breast cancer (R2 = 0.37; F = 6.83; p < 0.001). CONCLUSIONS: FT was more prevalent among women from low-income career. Women with poor family resilience, no religious also suffer greater financial toxicity. It is necessary to pay more attention of the financial toxicity of female' low-income career, no religious belief and poor family resilience. Developing effective interventions based on family resilience might be helpful in promoting their well-being.


Assuntos
Neoplasias da Mama , Emoções , Resiliência Psicológica , Humanos , Feminino , Neoplasias da Mama/psicologia , Neoplasias da Mama/economia , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Depressão/psicologia , Inquéritos e Questionários , Família/psicologia , Renda/estatística & dados numéricos , China , Estresse Financeiro/psicologia , Religião
4.
Front Immunol ; 15: 1340908, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650933

RESUMO

Background: Eltrombopag has demonstrated efficacy in treating low platelet (PLT) levels, but it remains unclear whether eltrombopag can promote PLT engraftment after hematopoietic stem cell transplantation (HSCT). Methods: Forty-one HSCT patients received eltrombopag 50 mg/d from +1 day until PLT >50 × 109/L or 1 month after HSCT. Fifty-one patients in the same period received thrombopoietin (TPO) to promote PLT graft after HSCT and served as a control group. Results: A total of 51 patients who applied TPO during the same period were treated as a control. In the eltrombopag group, the median time to white blood cells (WBC) graft was 12 days (range, 10-17 days) and the PLT graft was 15 days (range, 10-30 days), whereas for the patients in the TPO group, the median time to WBC and PLT graft was 12 days (range, 9-23 days) and 15.5 days (range, 9-41 days), respectively. In the first month after HSCT, the median WBC count in the eltrombopag group was 4.41 × 109/L (range, 0.87-40.01 × 109/L) and the median PLT was 89x109/L (range, 30-401 × 109/L); the median WBC and PLT \counts in the TPO group were 4.65 × 109/L (range, 0.99-23.63 × 109/L) and 86 × 109/L (range, 5-512 × 109/L), respectively. Patients in the TPO or eltrombopag group did not experience serious side effects after drug administration, and the difference in side effects on liver and kidney function between the two groups was not statistically significant. Conclusion: Eltrombopag is safe and similarly promotes platelet engraftment to thrombopoietin after allogeneic HSCT.


Assuntos
Benzoatos , Transplante de Células-Tronco Hematopoéticas , Hidrazinas , Pirazóis , Trombopoetina , Feminino , Humanos , Masculino , Benzoatos/uso terapêutico , Plaquetas/metabolismo , Plaquetas/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Hidrazinas/uso terapêutico , Contagem de Plaquetas , Pirazóis/uso terapêutico , Pirazóis/farmacologia , Trombopoetina/uso terapêutico , Transplante Homólogo
5.
Cryobiology ; 115: 104895, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38616031

RESUMO

The study is devoted to the effect of lowered resuscitation temperature (26 °C) on cryopreserved porcine adrenal glands functional activity in vitro and in vivo under xenotransplantation. The adrenals were collected from newborn pigs, cryopreserved with 5 % DMSO at a rate of 1 °C/min, resuscitated at 26 or 37 °C for 48 h (5 % CO2, DMEM), embedded into small intestinal submucosa, and transplanted to bilaterally adrenalectomized rats. It has been shown that the glands resuscitated at 26 °C have suppressed free-radical processes and can produce cortisol and aldosterone in vitro, and may lead to elevated blood levels of these hormones. Moreover, the adrenal grafts maintain blood glucose levels and promote the formation of glycogen stores. Thus, the resuscitation at 26 °C can improve the quality of grafts and favor the introduction and application of the cryopreserved organs and tissues for transplantation in clinical and experimental practice.


Assuntos
Glândulas Suprarrenais , Criopreservação , Hidrocortisona , Transplante Heterólogo , Animais , Glândulas Suprarrenais/metabolismo , Transplante Heterólogo/métodos , Criopreservação/métodos , Suínos , Hidrocortisona/sangue , Ratos , Glicemia/metabolismo , Glicemia/análise , Aldosterona/sangue , Aldosterona/metabolismo , Masculino , Glicogênio/metabolismo , Ressuscitação/métodos , Preservação de Órgãos/métodos , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-38372937

RESUMO

The increasing infection and drug resistance frequency has encouraged the exploration of new and effective anti-Candida albicans agents. In this study, CT-K3K7, a scorpion antimicrobial peptide derivative, effectively inhibit the growth of C. albicans. CT-K3K7 killed C. albicans cells in a dose-dependent manner, mainly by damaging the plasma membrane. CT-K3K7 could also disrupt the nucleus and interact with nucleic acid. Moreover, CT-K3K7 induced C. albicans cells necrosis via a reactive oxygen species (ROS)-related pathway. Furthermore, CT-K3K7 inhibited the hyphal and biofilm formation of C. albicans. In the mouse skin subcutaneous infection model, CT-K3K7 significantly prevented skin abscess formation and reduced the number of C. albicans cells recovered from the infection area. Taken together, CT-K3K7 has the potential to be a therapeutic for C. albicans skin infections.

7.
Toxicon ; 238: 107593, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38163461

RESUMO

As an alternative class of antimicrobial agents, antimicrobial peptides (AMPs) have gained significant attention. In this study, K1K8, a scorpion AMP derivative, showed effective activity against Candida albicans including clinically resistant strains. K1K8 killed C. albicans cells mainly by damaging the cell membrane and inducing necrosis via an ROS-related pathway. K1K8 could also interact with DNA after damaging the nuclear envelope. Moreover, K1K8 inhibited hyphal development and biofilm formation of C. albicans in a dose-dependent manner. In the mouse skin infection model, K1K8 significantly decreased the counts of C. albicans cells in the infection area. Overall, K1K8 is a potential anti-infective agent against skin infections caused by C. albicans.


Assuntos
Anti-Infecciosos , Antifúngicos , Animais , Camundongos , Antifúngicos/farmacologia , Candida albicans , Escorpiões , Peptídeos/farmacologia , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana
8.
Sci Data ; 10(1): 455, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37443183

RESUMO

The development of high-throughput omics technology has greatly promoted the development of biomedicine. However, the poor reproducibility of omics techniques limits their application. It is necessary to use standard reference materials of complex RNAs or proteins to test and calibrate the accuracy and reproducibility of omics workflows. The transcriptome and proteome of most cell lines shift during culturing, which limits their applicability as standard samples. In this study, we demonstrated that the human hepatocellular cell line MHCC97H has a very stable transcriptome (r = 0.983~0.997) and proteome (r = 0.966~0.988 for data-dependent acquisition, r = 0.970~0.994 for data-independent acquisition) after 9 subculturing generations, which allows this steady standard sample to be consistently produced on an industrial scale in long term. Moreover, this stability was maintained across labs and platforms. In sum, our study provides omics standard reference material and reference datasets for transcriptomic and proteomics research. This helps to further standardize the workflow and data quality of omics techniques and thus promotes the application of omics technology in precision medicine.


Assuntos
Multiômica , Proteoma , Transcriptoma , Humanos , Multiômica/métodos , Proteoma/genética , Proteômica/métodos , Reprodutibilidade dos Testes
9.
Cell Rep ; 42(6): 112647, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37330908

RESUMO

Dermal adipocyte lineage cells are highly plastic and can undergo reversible differentiation and dedifferentiation in response to various stimuli. Using single-cell RNA sequencing of developing or wounded mouse skin, we classify dermal fibroblasts (dFBs) into distinct non-adipogenic and adipogenic cell states. Cell differentiation trajectory analyses identify IL-1-NF-κB and WNT-ß-catenin as top signaling pathways that positively and negatively associate with adipogenesis, respectively. Upon wounding, activation of adipocyte progenitors and wound-induced adipogenesis are mediated in part by neutrophils through the IL-1R-NF-κB-CREB signaling axis. In contrast, WNT activation, by WNT ligand and/or ablation of Gsk3, inhibits the adipogenic potential of dFBs but promotes lipolysis and dedifferentiation of mature adipocytes, contributing to myofibroblast formation. Finally, sustained WNT activation and inhibition of adipogenesis is seen in human keloids. These data reveal molecular mechanisms underlying the plasticity of dermal adipocyte lineage cells, defining potential therapeutic targets for defective wound healing and scar formation.


Assuntos
Quinase 3 da Glicogênio Sintase , NF-kappa B , Camundongos , Animais , Humanos , NF-kappa B/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Diferenciação Celular/fisiologia , Adipócitos/metabolismo , Via de Sinalização Wnt/fisiologia , Adipogenia/genética , Interleucina-1/metabolismo , beta Catenina/metabolismo
10.
J Hazard Mater ; 454: 131485, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37149945

RESUMO

Foodborne pathogenic bacteria are recognized as the main causes of microbial contamination in food safety. Early screening and ultrasensitive detection of foodborne pathogenic bacteria is critical procedure to guarantee food safety. Argonaute is emerging as a new tool for detection owing to the programmability and high specificity. We reported a Novel and One-step cleavage method based on Argonaute by integrating Tag-specific primer extension and Exonuclease I (Exo I) for the first time, termed as NOTE-Ago. In this method, the invA of Salmonella typhi and nuc gene of Staphylococcus aureus were amplified using Tag-specific primer and the remaining primers were digested by Exo I. Then amplicons were served as the guide DNA for PfAgo. Consequently, the fluorophore-quencher reporter could be cleaved via PfAgo, resulting in changes in fluorescent intensity. With this strategy, target nucleic acid could be dexterously converted into fluorescent signals. The NOTE-Ago assay could detect 1 CFU/mL with a dynamic range from 1 to 108 CFU/mL. The satisfactory selectivity of NOTE-Ago assay further facilitated its application for detecting S. typhi- and S. aureus-contaminated food samples. This work enriches the toolbox of Argonaute-based detection and provides a one-step cleavage and rebuilding-free method for ultrasensitive detection of bacteria.


Assuntos
Bactérias , Staphylococcus aureus , Staphylococcus aureus/genética , Corantes Fluorescentes , Microbiologia de Alimentos
11.
Cell Death Discov ; 9(1): 176, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37248230

RESUMO

Sorafenib is the first FDA-approved first-line targeted drug for advanced HCC. However, resistance to sorafenib is frequently observed in clinical practice, and the molecular mechanism remains largely unknown. Here, we found that PLEKHG5 (pleckstrin homology and RhoGEF domain containing G5), a RhoGEF, was highly upregulated in sorafenib-resistant cells. PLEKHG5 overexpression activated Rac1/AKT/NF-κB signaling and reduced sensitivity to sorafenib in HCC cells, while knockdown of PLEKHG5 increased sorafenib sensitivity. The increased PLEKHG5 was related to its acetylation level and protein stability. Histone deacetylase 2 (HDAC2) was found to directly interact with PLEKHG5 to deacetylate its lysine sites within the PH domain and consequently maintain its stability. Moreover, knockout of HDAC2 (HDAC2 KO) or selective HDAC2 inhibition reduced PLEKHG5 protein levels and thereby enhanced the sensitivity of HCC to sorafenib in vitro and in vivo, while overexpression of PLEKHG5 in HDAC2 KO cells reduced the sensitivity to sorafenib. Our work showed a novel mechanism: HDAC2-mediated PLEKHG5 posttranslational modification maintains sorafenib resistance. This is a proof-of-concept study on targeting HDAC2 and PLEKHG5 in sorafenib-treated HCC patients as a new pharmaceutical intervention for advanced HCC.

12.
PLoS One ; 18(4): e0284871, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37083591

RESUMO

Focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase, which is overexpressed in colorectal cancer cells. FAK could be activated by phosphorylation to participate in the transduction of multiple signaling pathways and self-renewal of cancer stem cells. Whether the downregulation of FAK inhibits the metastasis in colorectal cancer through the weakening of stem cell-like properties and its mechanisms has yet to be established. CD44, CD133, c-Myc, Nanog, and OCT4 were known to mark colorectal cancer stem cell properties. In this study, AKT inhibitor (MK-2206 2HCl) or FAK inhibitor (PF-562271) decreased the expression of stem cell markers (Nanog, OCT4, CD133, CD44, c-Myc) and spheroid formation in colorectal cancer. Moreover, FAK and AKT protein was shown to interact verified by co-immunoprecipitation. Furthermore, downregulation of FAK, transfected Lenti-FAK-EGFP-miR to colorectal cancer cells, reduced p-AKT but not AKT and decreased the expression of stem cell markers and spheroid formation in colorectal cancer. In conclusion, we demonstrated that downregulation of FAK inhibited stem cell-like properties and migration of colorectal cancer cells partly due to altered modulation of AKT phosphorylation by FAK.


Assuntos
Neoplasias Colorretais , Transdução de Sinais , Humanos , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/patologia , Regulação para Baixo , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Fosforilação , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo
13.
J Hazard Mater ; 452: 131195, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36963196

RESUMO

The pandemic of COVID-19 creates an imperative need for sensitive and portable detection of SARS-CoV-2. We devised a SERS-read, CRISPR/Cas-powered nanobioassay, termed as OVER-SARS-CoV-2 (One-Vessel Enhanced RNA test on SARS-CoV-2), which enabled supersensitive, ultrafast, accurate and portable detection of SARS-CoV-2 in a single vessel in an amplification-free and anti-interference manner. The SERS nanoprobes were constructed by conjugating gold nanoparticles with Raman reporting molecular and single-stranded DNA (ssDNA) probes, whose aggregation-to-dispersion changes can be finely tuned by target-activated Cas12a though trans-cleavage of linker ssDNA. As such, the nucleic acid signals could be dexterously converted and amplified to SERS signals. By customizing an ingenious vessel, the steps of RNA reverse transcription, Cas12a trans-cleavage and SERS nanoprobes crosslinking can be integrated into a single and disposal vessel. It was proved that our proposed nanobioassay was able to detect SARS-CoV-2 as low as 200 copies/mL without any pre-amplification within 45 min. In addition, the proposed nanobioassay was confirmed by clinical swab samples and challenged for SARS-CoV-2 detection in simulated complex environmental and food samples. This work enriches the arsenal of CRISPR-based diagnostics (CRISPR-Dx) and provides a novel and robust platform for SARS-CoV-2 decentralized detection, which can be put into practice in the near future.


Assuntos
COVID-19 , Nanopartículas Metálicas , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Sistemas CRISPR-Cas , Ouro , Bioensaio , RNA , Técnicas de Amplificação de Ácido Nucleico
14.
Pharmaceutics ; 15(2)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36839900

RESUMO

Aluminum salt (AS), one of the most commonly used vaccine adjuvants, has immuno-modulatory activity, but how the administration of AS alone may impact the activation of the skin immune system under inflammatory conditions has not been investigated. Here, we studied the therapeutic effect of AS injection on two distinct skin inflammatory mouse models: an imiquimod (IMQ)-induced psoriasis-like model and an MC903 (calcipotriol)-induced atopic dermatitis-like model. We found that injection of a high dose of AS not only suppressed the IMQ-mediated development of T-helper 1 (Th1) and T-helper 17 (Th17) immune responses but also inhibited the IMQ-mediated recruitment and/or activation of neutrophils and macrophages. In contrast, AS injection enhanced MC903-mediated development of the T-helper 2 (Th2) immune response and neutrophil recruitment. Using an in vitro approach, we found that AS treatment inhibited Th1 but promoted Th2 polarization of primary lymphocytes, and inhibited activation of peritoneal macrophages but not bone marrow derived neutrophils. Together, our results suggest that the injection of a high dose of AS may inhibit Th1 and Th17 immune response-driven skin inflammation but promote type 2 immune response-driven skin inflammation. These results may provide a better understanding of how vaccination with an aluminum adjuvant alters the skin immune response to external insults.

15.
Math Biosci Eng ; 20(1): 613-623, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36650781

RESUMO

In lumbar puncture surgery, compared with the conventional methodologies like computed tomography and magnetic resonance imaging, ultrasound imaging offers the advantages of being low cost, no radiation and real-time image generation. However, the use of ultrasound equipment in lumbar puncture involves a cumbersome and time-consuming process for the subjective imaging of the overall structure of the lumbar spine in order to determine the exact puncture point and path. Meanwhile, the robotic arm puncture system has the advantages of high precision, good stability and simple and efficient operation. As a result, robotic-assisted ultrasound scanning is valuable for the assessment of a puncture path in spinal tap surgery. In this pursuit, based on the official URSDK development package for a robot arm and the Transmission Control Protocol/Internet Protocol, the system proposed in the present study involves a program to control the robot arm to clamp down onto an ultrasonic probe to enable automatic scanning and acquisition of images. A three-dimensional reconstruction program based on the visualization toolkit was designed, and a lumbar spine experiment was conducted with this system. A total of 136 two-dimensional ultrasound images were collected in the lumbar spine model experiment by enhancing contrast of and denoising the original ultrasound images, and a linear interpolation algorithm was used to perform the three-dimensional reconstruction of the lumbar spine model. The reconstructed structure was defective, but the location of the spinous process gap was determined with the sagittal and coronal images. The feasibility of the system was verified by the reconstruction results, which can provide a reference for determining the puncture point and path planning in the lumbar puncture surgery.


Assuntos
Vértebras Lombares , Punção Espinal , Punção Espinal/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Ultrassonografia/métodos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X
16.
J Agric Food Chem ; 71(8): 3551-3563, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36657010

RESUMO

Foodborne viruses have been recognized as important threats to food safety and human health. Rapid and accurate detection is one of the most crucial measures for food safety control. With the development of biology, chemistry, nanoscience, and related interdisciplines, detection strategies have been devised and advanced continuously. This review mainly focuses on the progress of detection methods for foodborne viruses. The current detection methods for foodborne viruses are summarized, including traditional electron microscopy and cultural isolation, immunoassay, molecular technology, biosensors, and newly emerging CRISPR/Cas-based detection technology. Furthermore, a comparison of the detection methods was objectively discussed. This review provides a comprehensive account of foodborne virus detection methods from fundamentals to state-of-the-art and illustrates the advantages and disadvantages of the current methods and proposes the future trends and directions for foodborne virus detection. It is hoped that this review can update current knowledge and present blueprints in order to accelerate futuristic development.


Assuntos
Técnicas Biossensoriais , Vírus , Humanos , Microbiologia de Alimentos , Inocuidade dos Alimentos , Vírus/genética , Técnicas Biossensoriais/métodos , Imunoensaio
17.
Eur J Haematol ; 110(4): 435-443, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36576398

RESUMO

BACKGROUND: It is known that the microenvironmental cytokine interferon gamma (IFN-γ) provides a survival advantage for chronic lymphocytic leukemia (CLL) cells. However, the mechanisms involved in this effect have not been properly investigated. METHODS: Herein, we conducted a comprehensive screening of the effects of IFN-γ on signaling pathways and gene expression profiles in CLL cells by using western blotting, real-time quantitative reverse transcription (RT-qPCR) and high-throughput RNA sequencing (RNA-seq). RESULTS: We found that IFN-γ not only activated the pro-survival signal transducer and activator of transcription 3 (STAT3), but also activated the protein kinase B and extracellular signal-regulated kinase signaling pathways. RNA-seq analysis showed that IFN-γ stimulation changed the expression profiles of more than 500 genes, with 391 being up-regulated and 123 down-regulated. These genes are involved in numerous biological processes, including anti-apoptosis, cell migration, and proliferation. IFN-γ significantly up-regulated the expression of CD38, BCL6, CXCL9, BCL2A1, SCOS3, IL-10, HGF, EGFR, THBS-1, FN1, and MUC1, which encode proteins potentially associated with disease progression, worse prognosis or poor response to treatment. Blocking janus kinases1/2 (JAK1/2) or STAT3 signal by specific inhibitors affected the expression of most genes, suggesting a pivotal role of the JAK1/2-STAT3 pathway in IFN-γ pro-survival effects in CLL. CONCLUSIONS: Our data demonstrate that IFN-γ regulates a complex pro-survival signal network in CLL through JAK1/2-STAT3, which provides a rational explanation for IFN-γ promoting CLL cells survival and drug resistance.


Assuntos
Interferon gama , Leucemia Linfocítica Crônica de Células B , Humanos , Citocinas/metabolismo , Interferon gama/imunologia , Leucemia Linfocítica Crônica de Células B/metabolismo , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/farmacologia
18.
J Hazard Mater ; 443(Pt B): 130234, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36372024

RESUMO

Rapid, sensitive and specific detection of bacteria is of great importance. Herein, we developed a versatile biosensing platform for ultrasensitive detection of pathogenic bacteria, termed as SCENT-Cas (Silver nanoCluster Empowered Nucleic acids Test using CRISPR/Cas12a). Simply, the species-specific invA gene of Salmonella typhimurium (S. typhi) was isothermally amplified using LAMP, which subsequently triggered the trans-cleavage of CRISPR/Cas12a. The trans-cleavage degraded any single-stranded DNA (ssDNA) non-specifically. A DNA-templated AgNCs probe was then employed, in which green fluorescence emissive AgNCs effectively converted to red fluorescence emissive AgNCs when placed in close vicinity to a pre-designed converter ssDNA. As such, the trans-cleavage was utilized for shredding converter ssDNA, enabling the green-to-red fluorescent change to form a ratiometric biosensing platform. With this strategy, target nucleic acid was dexterously converted into ratiometric fluorescence that was recorded to detect as low as 1 CFU/mL S. typhi with a dynamic range from 1 to 108 CFU/mL. To our knowledge, this is the first report regarding the use of ratiometric fluorescence in CRISPR/Cas-based detection, which minimizes interference and improves reliability. Lastly, this proposed strategy was challenged by detecting S. typhi contamination in real food samples. Our work enriches CRISPR/Cas toolbox in biosensing by providing a desirable method for bacterial detection.


Assuntos
Técnicas Biossensoriais , Prata , Salmonella typhimurium/genética , Sistemas CRISPR-Cas , Reprodutibilidade dos Testes , Técnicas Biossensoriais/métodos
19.
Microb Pathog ; 173(Pt A): 105865, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36332790

RESUMO

A large number of evidence showed that regulatory sRNAs could modulate antibiotic resistance and sensitivity. In this study, we used RNA-sequencing to profile sRNAs in wild type and antibiotic-resistant PAO1 selected by four antibiotics (polymyxin B, ciprofloxacin, doxycycline, and ceftriaxone). Totally, we found 113, 25, 91 and 12 differentially expressed sRNAs in polymyxin B-, ciprofloxacin-, doxycycline-, and ceftriaxone-resistant P. aeruginosa, respectively. To elucidate functions of differentially expressed sRNA, we predicated their target genes and obtained pathways enriched by their target genes. In addition, our results indicated that the downregulated sRNA spae884.1, spae3443.1, and spae5681.1 might involve in polymyxin B resistance by enhancing their target genes arnA, arnD, and arnT expression in PAO1, respectively. The upregulated sRNA spae3443.1 and spae649.2 might implicate in ciprofloxacin resistance by promoting their target gene pslK expression to increase biofilm formation in PAO1. The upregulated spae1558.1 might increase oprJ expression, as well as spae3959.1 and spae3706.1 might increase mexC expression to modulate doxycycline resistance in PAO1. The sRNA novel-N714 might involve in virulence in ceftriaxone-resistant PAO1 by activating its target gene PA1429 expression. Our study might provide bases of the underlying mechanism of sRNA in regulating antibiotic resistance of PAO1 against different antibiotics.


Assuntos
Antibacterianos , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Polimixina B/farmacologia , Ceftriaxona , Doxiciclina/farmacologia , Ciprofloxacina/farmacologia , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica
20.
Front Oncol ; 12: 1019006, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36276107

RESUMO

Objective: The aim of this study was to explore the symptoms and experiences of frailty in lung cancer patients treated with chemotherapy. Methods: Quantitative and qualitative research methods were implemented. A total of 302 patients aged > 18 years were recruited by convenience sampling method. Quantitative data were collected through the General Demographic Characteristics questionnaire, the Frailty Phenotype scale, the Cancer Fatigue Scale, the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. Fourteen patients with a score of Frailty Phenotype scale ≥ 3 were drawn and their interviews were thematically analyzed. Results: The mean Frailty Phenotype score was (1.63±1.35), suggesting that most of the patients were in pre-frailty conditions. A total of 64 (21.2%) patients were non-frail, 168 (55.6%) patients were pre-frail, 70 (23.2%) patients were frail. The mean CFS, HADS scores, and PSQI scores were (26.86±8.93), (15.42±9.73), and (6.18±4.39), respectively. The Number of chemotherapy times was positively associated with frailty. Anxiety fatigue, depression and poor sleep quality positively correlated with frailty. The qualitative research showed four themes. Theme 1: the most reported symptoms of frailty were physical symptoms and psychological symptoms. Physical symptoms included fatigue, low physical activity, weight loss and poor sleep quality. Psychological symptoms included anxiety, depression and low social activities. Theme 2: frailty was mainly related to lung cancer and chemotherapeutic drugs, which can cause decreased appetite, constipation and altered taste. Theme 3: patients used bad coping strategies to manage the symptoms of frailty. Theme 4: the social support of patients was weak, especially regarding emotional support. Conclusion: The most frequent symptoms reported by lung cancer patients treated with chemotherapy were anxiety, fatigue, depression, low physical activity and poor sleep quality. Patients also complained of bad coping strategies and weak support. Medical staff should strengthen the management of frailty, aiming at improving the quality of life in lung cancer patients treated with chemotherapy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA