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1.
Pediatr Hematol Oncol ; : 1-13, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39360430

RESUMO

Measurable residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an independent risk factor for relapse in patients with acute lymphoblastic leukemia (ALL). This study aimed to assess the efficacy, safety, and immune reconstitution of chimeric antigen receptor T-cell (CAR-T) therapy in patients with molecular relapse after allo-HSCT. Eleven patients with molecular relapse of B-cell-ALL who underwent CAR-T therapy after allo-HSCT were enrolled. The rate of MRD negativity after a month of CAR-T infusion was 81.8%. Patients who bridged to second-HSCT after CAR-T therapy (n = 3) showed a trend of higher 3-year leukemia-free survival and 3-year overall survival than those who did not (n = 8; 100% vs. 75.0%; 95% CI, 45.0-104.9%; p = 0.370). No treatment-related mortalities were observed. Among patients who did not bridge to second-HSCT and remained in complete remission until the last follow-up (n = 6), five of them had not recovered normal immunoglobulin concentrations with a median follow-up of 43 months. CAR-T therapy may be a safe and effective treatment strategy to improve survival after allo-HSCT; however, the problem of prolonged hypogammaglobulinemia in patients who do not bridge to second-HSCT is worth noting.

2.
BMC Womens Health ; 24(1): 544, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354424

RESUMO

OBJECTIVE: To exploit the combination diagnostic performance of serum microRNA-134-5p (miR-134-5p) and color Doppler ultrasound in patients with endometriosis patients. METHODS: Quantitative real time polymerase chain reaction (qRT-PCR) analysis was applied to measure relative abundance of miR-134-5p in serum of patients with endometriosis and gynecological benign diseases. Calculation of uterine artery blood flow parameters was conducted using Color Doppler ultrasound. Receiver operating characteristic (ROC) curve was established to evaluate the diagnostic capacity of miR-134-5p and Doppler parameters. Kaplan-Meier method was used for the analysis of recurrence-free survival rate. RESULTS: Compared with the control group, serum miR-134-5p expression was remarkably diminished in endometriosis patients (P < 0.001). End-diastolic velocity (EDV) and peak systolic velocity (PSV) were notably decreased in endometriosis patients compared with the control group (P < 0.001), while pulsatility index (PI) and resistance index (RI) were distinctly increased (P < 0.001). Serum miR-134-5p expression was positively correlated with EDV (r = 0.5777, P < 0.0001) and PSV (r = 0.6945, P < 0.0001), but negatively correlated with PI (r=-0.6382, P < 0.0001) and RI (r=-0.6247, P < 0.0001). The area under the ROC curve (AUC) of serum miR-134-5p combined with Doppler parameters was 0.905, with the sensitivity of 87.40%, and the specificity of 82.29%. The recurrence-free survival time was shorter in patients with low miR-134-5p expression than those with high miR-134-5p expression (P = 0.013). CONCLUSION: A better diagnostic value of endometriosis detection could be obtained when serum miR-134-5p was combined with Doppler parameters.


Assuntos
Endometriose , MicroRNAs , Ultrassonografia Doppler em Cores , Artéria Uterina , Humanos , Feminino , MicroRNAs/sangue , Ultrassonografia Doppler em Cores/métodos , Adulto , Endometriose/sangue , Endometriose/diagnóstico por imagem , Artéria Uterina/diagnóstico por imagem , Curva ROC , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos de Casos e Controles , Biomarcadores/sangue , Relevância Clínica
4.
Int J Biol Macromol ; 280(Pt 1): 135734, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293619

RESUMO

With the increasing threat of white pollution to the public health and ecosystem, functional materials driven by green and sustainable biological macromolecule are attracting considerable attention. Inspired by the double-helix structure of DNA, a P-B-N ternary synergistic chitosan-based macromolecule (PBCS) was constructed to prepare flame retardant, smoke suppression and self-healing polyvinyl alcohol composite (PVA@PBCS) via dynamic reversible interactions. The limiting oxygen index value of PVA@PBCS increased from 19.6 % to 28.7 %, whereas the peak heat release rate and total heat release decreased by 47.04 % and 43.37 %, respectively. Besides, the peak smoke production rate and total smoke production of PVA@PBCS also decreased by 45.31 % and 54.98 %. With the presence of borate ester-based covalent and multiple hydrogen bonds, the tensile strength and elongation at break of PVA@PBCS increased by 19.50 % and 16.85 % compared to the control sample, and the healing efficiency for tensile strength and elongation at break was as high as 93.86 % and 90.57 %, respectively. This work developed an eco-friendly and effective scenario for fabricating flame retardant and smoke suppression PVA materials, stimulating the substantial potential of chitosan-based biomacromolecule and dynamic reversible cross-linked tactics in self-healing field.

5.
Biosci Rep ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39312181

RESUMO

Aging is an inevitable and irreversible biological process that gradually heightens the risks of various diseases and death. As a newly discovered endogenous gasotransmitter, hydrogen sulfide (H2S) has been identified to exert multiple beneficial impacts on the regulation of aging and age-related pathologies. This study was aimed at systematically exploring the relationship between asynchronous aging processes and H2S concentrations in various tissues of aging mice. Samples of plasma and thirteen tissues were collected from four cross-sectional age groups (3, 6, 12 and 18 months of age) covering the lifespan of male C57BL/6J mice. The H2S concentration was quantified by a reported liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with monobromobimane (MBB) derivatization. Additionally, the expressions of CSE, CBS and 3-MST in those tissues were analyzed by western blotting. We discovered that the H2S concentrations decreased asynchronously with the aging process in plasma, heart, liver, kidney, spleen, subcutaneous fat and brown fat and increased in brain and lung. At least one of the three H2S-generating enzymes expressions was compensatorily upregulated with the aging process in most tissues, among which the up-regulation of CSE was the most prominent.

6.
J Magn Reson Imaging ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304527

RESUMO

In patients with acute myocardial infarction (AMI), traditional clinical endpoints used to assess drug efficacy and prognosis include infarct size (IS), incidence of heart failure, and mortality rates. Although these metrics are commonly employed to evaluate outcomes in AMI patients, their utility is limited in small-scale studies. The introduction of the myocardial salvage index (MSI) reduces variability in assessments across multiple dimensions, thereby enhancing the sensitivity of outcome measures and reducing the required sample size. Moreover, MSI is increasingly utilized to evaluate drug efficacy, prognosis, and risk stratification in AMI patients. Although a variety of methodologies for measuring the MSI are currently available, the incorporation of these methods as clinical endpoints remains limited. In the clinical application of cardioprotective strategies, it is recommended that MSI be evaluated using late gadolinium enhancement measured along the endocardial surface length combined with IS in cardiac magnetic resonance. In dynamic single-photon emission computed tomography, an assessment of MSI using methods based on abnormalities in myocardial wall thickening combined with perfusion anomalies is advocated. This review comprehensively outlines the principles, advantages, and limitations of different MSI assessment methods and discusses the prospects and challenges of MSI in cardiac protective therapies. Additionally, we summarize recommended strategies for employing MSI as a clinical surrogate endpoint in various clinical scenarios, providing direction for future clinical practice and research. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 4.

7.
Mol Cell Endocrinol ; 594: 112381, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39341450

RESUMO

This study aimed to elucidate the role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in polycystic ovary syndrome (PCOS). A rat model PCOS was constructed by subcutaneous injection with dehydroepiandrosterone (DHEA). Follicular atresia and reduced granular cells (GCs) in ovaries suggested successful modeling. The low expression of TIGAR was observed in ovarian tissue of PCOS rat. To explore the role of TIGAR in PCOS, lentivirus carrying the TIGAR were used to up-regulate TIGAR expression. TIGAR overexpression reduced the DHEA-induced increase of ovarian weight, the levels of estradiol (E2), and the ratio of luteinizing hormone/follicle-stimulating hormone (LH/FSH) in the serum, as well as improved the morphology of the follicle, especially increased the thickness of the GC layer, which attributed to the inhibition of apoptosis by TIGAR. In addition, high expression of TIGAR inhibited oxidative stress in ovaries of PCOS rat, as evidenced by decreased level of malondialdehyde (MDA), and reactive oxygen species (ROS), and enhanced activity of glutathione peroxidase (GPX) and superoxide dismutase (SOD). Mechanically, Nrf2/OH-1 signal pathway was activated by TIGAR. The effect of TIGAR on PCOS were verified in the primary rat GCs treated with dihydrotestosterone, but also the rescue experiment was performed. Downregulation of Nrf2 reversed the effects of TIGAR, indicating that TIGAR suppressed oxidative stress and GC apoptosis by activating Nrf2/OH-1 pathway in PCOS. Finally, non-targeted metabolomics revealed that TIGAR might affect the energy metabolic pathway, thereby altering the metabolic profile of primary rat GCs. This study provided new insights into the prevention and treatment of PCOS.

8.
Elife ; 132024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39347738

RESUMO

Some transcription factors (TFs) can form liquid-liquid phase separated (LLPS) condensates. However, the functions of these TF condensates in 3-Dimentional (3D) genome organization and gene regulation remain elusive. In response to methionine (met) starvation, budding yeast TF Met4 and a few co-activators, including Met32, induce a set of genes involved in met biosynthesis. Here, we show that the endogenous Met4 and Met32 form co-localized puncta-like structures in yeast nuclei upon met depletion. Recombinant Met4 and Met32 form mixed droplets with LLPS properties in vitro. In relation to chromatin, Met4 puncta co-localize with target genes, and at least a subset of these target genes is clustered in 3D in a Met4-dependent manner. A MET3pr-GFP reporter inserted near several native Met4-binding sites becomes co-localized with Met4 puncta and displays enhanced transcriptional activity. A Met4 variant with a partial truncation of an intrinsically disordered region (IDR) shows less puncta formation, and this mutant selectively reduces the reporter activity near Met4-binding sites to the basal level. Overall, these results support a model where Met4 and co-activators form condensates to bring multiple target genes into a vicinity with higher local TF concentrations, which facilitates a strong response to methionine depletion.


Assuntos
Regulação Fúngica da Expressão Gênica , Metionina , Regulon , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Fatores de Transcrição , Metionina/metabolismo , Metionina/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição de Zíper de Leucina Básica
9.
Talanta ; 281: 126844, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39277931

RESUMO

Self-powered biosensors with high sensitivity have garnered significant interest for their potential applications in the realm of portable sensing. Herein, a self-powered biosensor with a novel signal amplification strategy was developed by integrating target-controlled release of mediator with an enzyme biofuel cell for the ultrasensitive detection of acetamiprid (ACE). Zeolitic imidazolate framework-67 was utilized as both a nanocontainer for capturing the electron mediator 2,2'-azidobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and a precursor for the synthesis of cobalt nanoparticles/nitrogen, sulfur-codoped carbon nanotubes (Co NPs/NS-CNTs), which were employed as the electrode material for constructing both the glucose oxidase-based bioanode and the laccase-based biocathode. The target analyte ACE can specifically bind to its aptamer, leading to the release of ABTS, which cyclically participates in the catalytic reaction of the biocathode, thereby amplifying the electrochemical signal. By leveraging the benefits of ABTS cyclic catalysis and the effective electrocatalysis of bioelectrodes based on Co NPs/NS-CNTs, the self-powered biosensor has a broad detection range of 0.1-1000 fM and a low detection limit of 25 aM toward ACE. The proposed signal amplification approach presents a promising strategy for enhancing sensitivity and enabling portable analysis in applications of food safety, environmental monitoring, and medical diagnostics.

10.
Environ Sci Technol ; 58(39): 17419-17428, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39292546

RESUMO

Benzotriazole ultraviolet absorbers (BUVs), as emerging contaminants of extensive use, especially in plastic sports fields, have aroused increasing concern due to their potential human and environmental impacts. However, BUV exposure from plastic sports field dust is still unknown. This study compared BUVs in plastic sports field dust and indoor dust for the first time. The order of the geometric mean concentrations of the total BUVs (ΣBUVs) in plastic sports field dust was indoor badminton courts (11023 ng g-1) > basketball courts (4777 ng g-1) > plastic tracks (3779 ng g-1) > synthetic turf (1920 ng g-1) > tennis courts (689 ng g-1). The geometric mean concentrations of ΣBUVs in indoor dust (1150 ng g-1) were lower than those in most plastic sports field dust. The dominant BUV was 2-hydroxy-4-(octyloxy)benzophenone (UV-531) in plastic sports field dust, while 2,2'-methylenebis[4-(1,1,3,3-tetramethylbutyl)-6-2H-benzotriazole-2-yl)phenol] (UV-360) was the dominant BUV in indoor dust. Releases from plastic track materials, sneaker soles, and friction between them might be important BUV sources in plastic track dust. The average estimated daily intakes of ΣBUVs from plastic sports field dust for general exercisers were lower than those from indoor dust, but those for exercisers with long time or professional athletes might be higher, potentially posing health risks.


Assuntos
Poeira , Poeira/análise , Humanos , Plásticos , Poluição do Ar em Ambientes Fechados/análise , Triazóis/análise , Esportes , Raios Ultravioleta , Exposição Ambiental
11.
Foods ; 13(17)2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39272600

RESUMO

α-Glucosidase is an important target for type II diabetes treatment, and the search for natural α-glucosidase inhibitors is currently a hot topic in functional food research. Camellianin A is the main flavonoid in the leaves of Adinandra nitida, but research on its inhibition of α-glucosidase is rarely reported. In view of this, the present study systematically investigated the inhibitory impact of camellianin A on α-glucosidase, combining the fluorescence method and molecular docking to explore their interaction, aiming to reveal the relevant inhibitory mechanism. The results indicated that camellianin A possessed excellent α-glucosidase inhibitory activity (IC50, 27.57 ± 0.59 µg/mL), and van der Waals force and hydrogen bonding dominated the binding process between camellianin A and α-glucosidase, with a binding-site number of 1. A molecular docking experiment suggested that camellianin A formed hydrogen bonding with Glu771, Trp391, Trp710, Gly566, Asp568, and Phe444 of α-glucosidase, consistent with the thermodynamic result. Our result can provide a reference for the development of natural α-glucosidase inhibitors.

12.
Discov Oncol ; 15(1): 403, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225917

RESUMO

AIM: The purpose of the present study was to evaluate the diagnostic performance of serum miR-4534 combined with Transvaginal Color Doppler Ultrasound (TVCDS) in cervical cancer patients. METHODS: Blood samples from 126 patients with cervical cancer and 83 patients with benign uterine lesions were retrospectively analyzed. Quantitative real time polymerase chain reaction (qRT-PCR) was applied to examine the relative abundances of serum miR-4534 in cervical cancer based on a case-control study. Chi-square test was adopted to analyze the association between serum miR-4534 and other clinicopathological factors. The blood flow of cervix was examined using TVCDS, and the blood flow resistance index (RI) of cervix was summarized. Receiver operating characteristic (ROC) curves were plotted to explore the diagnostic capacity of serum miR-4534 combined with blood flow RI. Logistic regression was employed to analyze the risk factors of cervical cancer. RESULTS: Serum miR-4534 was distinctly increased in the study group compared with the control group (P < 0.05), while blood flow RI was dramatically decreased (P < 0.05). Moreover, increased miR-4534 was closely associated with lymph node metastasis (P = 0.010), FIGO stage (P = 0.007) and HR-HPV (P = 0.025). ROC curves demonstrated that the area under curve (AUC) of serum miR-4534 combined with the blood flow RI was 0.854, with the sensitivity and specificity of 88.9% and 73.5%, respectively, which displayed a better diagnostic capacity than serum miR-4534 and blood flow RI alone. Logistic regression analysis demonstrated that serum miR-4534 (OR = 8.805, 95% CI = 4.124-18.798; P < 0.001) was a risk factor related to the initiation and formation of cervical cancer, as well as blood flow RI (OR = 0.112; 95% CI = 0.054-0.235; P < 0.001). CONCLUSION: Serum miR-4534 was highly expressed in cervical cancer, and associated with the development and metastasis of cervical cancer patients. MiR-4534 combined with TVCDS exhibited a considerable biomarker to detect cervical cancer patients.

13.
Commun Biol ; 7(1): 1172, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294333

RESUMO

Clostridioides difficile infection (CDI) is a common healthcare-associated infection and the leading cause of gastroenteritis-related deaths worldwide. To investigate the effects of peptide composition of different protein products on CDI, we analyzed and compared the peptide sequences and compositions from Engraulis japonicus and Glycine max using Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). An animal model of CDI was also established to investigate the potential therapeutic effects of these peptides in vivo. The peptide compositions of E. japonicus and G. max differed, with only 11% of the peptide sequences being identical. Oral administration of the tested peptides could reduce intestinal inflammation, repair the intestinal barrier, increase the proportion of beneficial bacteria, and reduce the proportion of harmful bacteria, providing a therapeutic effect against CDI. However, the peptides may differ considerably in some aspects. E. japonicus peptides were superior to G. max peptides in promoting colon epithelial cell proliferation and repairing tight intestinal cell junctions. Interestingly, the two sources of peptides have different effects on the cecal microbiome. E. japonicus peptides can effectively restore the diversity and richness of intestinal microbiota, while G. max peptides have poor regulatory effects on the intestinal microbiota structure. Overall, E. japonicus peptides showed better results than G. max peptides in treating CDI. This study supports the potential treatment of CDI with natural peptides and promotes the development of specialty foods for CDI enteritis. Clostridioides difficile infection (CDI) is a common healthcare-associated infection and the leading cause of gastroenteritis-related deaths worldwide. To investigate the effects of peptide composition of different protein products on CDI, we analyzed and compared the peptide sequences and compositions from Engraulis japonicus and Glycine max using Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). An animal model of CDI was also established to investigate the potential therapeutic effects of these peptides in vivo. The peptide compositions of E. japonicus and G. max differed, with only 11% of the peptide sequences being identical. Oral administration of the tested peptides could reduce intestinal inflammation, repair the intestinal barrier, increase the proportion of beneficial bacteria, and reduce the proportion of harmful bacteria, providing a therapeutic effect against CDI. However, the peptides may differ considerably in some aspects. E. japonicus peptides were superior to G. max peptides in promoting colon epithelial cell proliferation and repairing tight intestinal cell junctions. Interestingly, the two sources of peptides have different effects on the cecal microbiome. E. japonicus peptides can effectively restore the diversity and richness of intestinal microbiota, while G. max peptides have poor regulatory effects on the intestinal microbiota structure.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Modelos Animais de Doenças , Microbioma Gastrointestinal , Peptídeos , Animais , Camundongos , Peptídeos/farmacologia , Peptídeos/química , Infecções por Clostridium/microbiologia , Infecções por Clostridium/tratamento farmacológico , Clostridioides difficile/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Espectrometria de Massas em Tandem , Masculino
14.
ACS Nano ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327724

RESUMO

Sonocatalytic therapy (SCT) has emerged as a promising noninvasive modality for tumor treatment but is hindered by the insufficient generation of ultrasound-induced reactive oxygen species (ROS) and the hypoxic tumor microenvironments. Herein, we fabricated a carbon nanoframe-confined N-coordinated manganese single-atom sonocatalyst with a five-coordinated structure (MnN5 SA/CNF) using a phthalocyanine-mediated pyrolysis strategy. The precise coordination structure was identified by synchrotron X-ray absorption fine structure analyses. The MnN5 SA/CNF exhibits superior and nonoxygen-dependent sonocatalytic activity owing to the optimized coordination structure and cavitation effect enhanced by defects. Additionally, density functional theory studies reveal that the five-coordination structure downshifts the d-band center of Mn from -0.547 to -0.829 eV and enhances the desorption capacity for oxygen-containing intermediates, thus accelerating the catalytic process. Finally, the as-synthesized MnN5 SA/CNF demonstrates a significantly enhanced antitumor effect through mitochondrial apoptosis in an orthotopic breast cancer mouse model. This work explores the potential of SAzymes-supported biomedical interventions by leveraging enzymatic activity with sonocatalytic properties.

15.
Redox Biol ; 75: 103299, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-39127016

RESUMO

Lung cancer is a leading cause of cancer death worldwide, with high incidence and poor survival rates. Cold atmospheric plasma (CAP) technology has emerged as a promising therapeutic approach for cancer treatment, inducing oxidative stress in malignant tissues without causing thermal damage. However, the role of CAP in regulating lung cancer cell ferroptosis remains unclear. Here, we observed that CAP effectively suppressed the growth and migration abilities of lung cancer cells, with significantly increased ferroptotic cell death, lipid peroxidation, and decreased mitochondrial membrane potential. Mechanistically, CAP regulates SLC7A11-mediated cell ferroptosis by modulating HOXB9. SLC7A11, a potent ferroptosis suppressor, was markedly reduced by HOXB9 knockdown, while it was enhanced by overexpressing HOXB9. The luciferase and ChIP assays confirmed that HOXB9 can directly target SLC7A11 and regulate its gene transcription. Additionally, CAP enhanced the acetylation modification level of HOXB9 by promoting its interaction with acetyltransferase p300/CBP-associated factor (PCAF). Acetylated HOXB9 affects its protein ubiquitination modification level, which in turn affects its protein stability. Notably, the upregulation of SLC7A11 and HOXB9 mitigated the suppressive effects of CAP on ferroptosis status, cell proliferation, invasion, and migration in lung cancer cells. Furthermore, animal models have also confirmed that CAP can inhibit the progression of lung cancer in vivo. Overall, this study highlights the significance of the downregulation of the HOXB9/SLC7A11 axis by CAP treatment in inhibiting lung cancer, offering novel insights into the potential mechanisms and therapeutic strategies of CAP for lung cancer.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Carcinoma Pulmonar de Células não Pequenas , Ferroptose , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio , Neoplasias Pulmonares , Fatores de Transcrição de p300-CBP , Humanos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Acetilação , Fatores de Transcrição de p300-CBP/metabolismo , Animais , Camundongos , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Linhagem Celular Tumoral , Proliferação de Células , Movimento Celular
16.
Eur Respir J ; 64(3)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39190789

RESUMO

BACKGROUND: Pulmonary ischaemia-reperfusion injury (IRI) is a major contributor to poor lung transplant outcomes. We recently demonstrated a central role of airway-centred natural killer (NK) cells in mediating IRI; however, there are no existing effective therapies for directly targeting NK cells in humans. METHODS: We hypothesised that a depleting anti-CD94 monoclonal antibody (mAb) would provide therapeutic benefit in mouse and human models of IRI based on high levels of KLRD1 (CD94) transcripts in bronchoalveolar lavage samples from lung transplant patients. RESULTS: We found that CD94 is highly expressed on mouse and human NK cells, with increased expression during IRI. Anti-mouse and anti-human mAbs against CD94 showed effective NK cell depletion in mouse and human models and blunted lung damage and airway epithelial killing, respectively. In two different allogeneic orthotopic lung transplant mouse models, anti-CD94 treatment during induction reduced early lung injury and chronic inflammation relative to control therapies. Anti-CD94 did not increase donor antigen-presenting cells that could alter long-term graft acceptance. CONCLUSIONS: Lung transplant induction regimens incorporating anti-CD94 treatment may safely improve early clinical outcomes.


Assuntos
Anticorpos Monoclonais , Células Matadoras Naturais , Transplante de Pulmão , Camundongos Endogâmicos C57BL , Subfamília D de Receptores Semelhantes a Lectina de Células NK , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Camundongos , Humanos , Subfamília D de Receptores Semelhantes a Lectina de Células NK/metabolismo , Subfamília D de Receptores Semelhantes a Lectina de Células NK/imunologia , Anticorpos Monoclonais/farmacologia , Masculino , Modelos Animais de Doenças , Pulmão/imunologia , Pulmão/patologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Feminino
17.
Sci Rep ; 14(1): 18699, 2024 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134573

RESUMO

The lip-splitting approach enables excellent access to all areas of the mouth and pharynx to remove tumors; however, traditional lower lip-splitting incisions produce an unsatisfactory scar. To achieve better functional and aesthetic results, we used a Z-shaped incision and compared the functional and aesthetic outcomes of the straight and Z-shaped incisions. Sixty patients who fulfilled the inclusion criteria were randomly divided into two groups and underwent lip-splitting between March 2021 and September 2023. Eventually, 77 patients were reviewed within 6 months and evaluated using the lip function assessment scale, patient and observer scar assessment scale, naïve observer scar assessment scale, and a clinical examination. The Z-shaped incision group performed better in terms of the lip pout movement at 3 months and in the subjective overall opinion, color, irregularity, and pigmentation at 6 months. The Z-shaped incision group had a lower incidence of notched vermilion. In conclusion, Z-shaped lower lip-splitting incisions have better functional and aesthetic outcomes than traditional straight incisions.Trial registration: Public title: Difference between the effect of Z-shaped and vertical incisions of labiobuccal flap on the recovery of lower lip scars. Registration date: 09/03/2021. Registration number: ChiCTR2100044084. Registry URL: http://www.chictr.org.cn .


Assuntos
Cicatriz , Estética , Lábio , Humanos , Lábio/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Procedimentos de Cirurgia Plástica/métodos , Idoso , Retalhos Cirúrgicos , Resultado do Tratamento
18.
Aging Cell ; : e14320, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39158018

RESUMO

Degenerative spinal stenosis is a chronic disease that affects the spinal ligaments and associated bones, resulting in back pain and disorders of the limbs among the elderly population. There are few preventive strategies for such ligament degeneration. We here aimed to establish a comprehensive transcriptomic atlas of ligament tissues to identify high-priority targets for pharmaceutical treatment of ligament degeneration. Here, single-cell RNA sequencing was performed on six degenerative ligaments and three traumatic ligaments to understand tissue heterogeneity. After stringent quality control, high-quality data were obtained from 32,014 cells. Distinct cell clusters comprising stromal and immune cells were identified in ligament tissues. Among them, we noted that collagen degradation associated with CTHRC1+ fibroblast-like cells and calcification linked to CRTAC1+ chondrocyte-like cells were key features of ligament degeneration. SCENIC analysis and further experiments identified ATF3 as a key transcription factor regulating the pathogenesis of CRTAC1+ chondrocyte-like cells. Typically, immune cells infiltrate localized organs, causing tissue damage. In our study, myeloid cells were found to be inflammatory-activated, and SPP1+ macrophages were notably enriched in degenerative ligaments. Further exploration via CellChat analysis demonstrated a robust interaction between SPP1+ macrophages and CRTAC1+ chondrocyte-like cells. Activated by SPP1, ATF3 propels the CRTAC1/MGP/CLU axis, fostering ligament calcification. Our unique resource provides novel insights into possible mechanisms underlying ligament degeneration, the target cell types, and molecules that are expected to mitigate degenerative spinal ligament. We also highlight the role of immune regulation in ligament degeneration and calcification, enhancing our understanding of this disease.

19.
JAMIA Open ; 7(3): ooae068, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39100988

RESUMO

Objective: The aims of this systematic review were to (1) synthesize the available qualitative evidence on the barriers and facilitators influencing implementation of the electronic collection and use of patient-reported measures (PRMs) in older adults' care from various stakeholder perspectives and (2) map these factors to the digital technology implementation framework Non-adoption, Abandonment, challenges to the Scale-up, Spread, Sustainability (NASSS) and behavior change framework Capability, Opportunity, Motivation, Behaviour (COM-B). Materials and Methods: A search of MEDLINE, CINAHL Plus, and Web of Science databases from 1 January 2001 to 27 October 2021 was conducted and included English language qualitative studies exploring stakeholder perspectives on the electronic collection and use of PRMs in older adults' care. Two authors independently screened studies, conducted data extraction, quality appraisal using the Critical Appraisal Skills Programme (CASP), data coding, assessed confidence in review findings using Grading of Recommendations Assessment, Development, and Evaluation Confidence in the Evidence from Reviews of Qualitative Research (GRADE CERQual), and mapped the findings to NASSS and COM-B. An inductive approach was used to synthesize findings describing the stakeholder perspectives of barriers and facilitators. Results: Twenty-two studies were included from the 3368 records identified. Studies explored older adult, caregiver, healthcare professional, and administrative staff perspectives. Twenty nine of 34 review findings (85%) were graded as having high or moderate confidence. Key factors salient to older adults related to clinical conditions and socio-cultural factors, digital literacy, access to digital technology, and user interface. Factors salient to healthcare professionals related to resource availability to collect and use PRMs, and value of PRMs collection and use. Conclusion: Future efforts to implement electronic collection and use of PRMs in older adults' care should consider addressing the barriers, facilitators, and key theoretical domains identified in this review. Older adults are more likely to adopt electronic completion of PRMs when barriers associated with digital technology access, digital literacy, and user interface are addressed. Future research should explore the perspectives of other stakeholders, including those of organizational leaders, digital technology developers and implementation specialists, in various healthcare settings and explore factors influencing implementation of PREMs. PROSPERO registration number: CRD42022295894.

20.
World J Gastrointest Surg ; 16(7): 2135-2144, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39087125

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a prevalent cancer type in clinical settings; its early signs can be difficult to detect, which often results in late-stage diagnoses in many patients. The early detection and diagnosis of CRC are crucial for improving treatment success and patient survival rates. Recently, imaging techniques have been hypothesized to be essential in managing CRC, with magnetic resonance imaging (MRI) and spiral computed tomography (SCT) playing a significant role in enhancing diagnostic and treatment approaches. AIM: To explore the effectiveness of MRI and SCT in the preoperative staging of CRC and the prognosis of laparoscopic treatment. METHODS: Ninety-five individuals admitted to Zhongshan Hospital Xiamen University underwent MRI and SCT and were diagnosed with CRC. The precision of MRI and SCT for the presurgical classification of CRC was assessed, and pathological staging was used as a reference. Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of blood volume, blood flow, time to peak, permeability surface, blood reflux constant, volume transfer constant, and extracellular extravascular space volume fraction on the prognosis of patients with CRC. RESULTS: Pathological biopsies confirmed the following CRC stages: 23, 23, 32, and 17 at T1, T2, T3, and T4, respectively. There were 39 cases at the N0 stage, 22 at N1, 34 at N2, 44 at M0 stage, and 51 at M1. Using pathological findings as the benchmark, the combined use of MRI and SCT for preoperative TNM staging in patients with CRC demonstrated superior sensitivity, specificity, and accuracy compared with either modality alone, with a statistically significant difference in accuracy (P < 0.05). Receiver operating characteristic curve analysis revealed the predictive values for laparoscopic treatment prognosis, as indicated by the areas under the curve for blood volume, blood flow, time to peak, and permeability surface, blood reflux constant, volume transfer constant, and extracellular extravascular space volume fraction were 0.750, 0.683, 0.772, 0.761, 0.709, 0.719, and 0.910, respectively. The corresponding sensitivity and specificity values were also obtained (P < 0.05). CONCLUSION: MRI with SCT is effective in the clinical diagnosis of patients with CRC and is worthy of clinical promotion.

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