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1.
Nat Immunol ; 24(11): 1813-1824, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37813965

RESUMO

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with ß-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP-galectin-9-dectin-2 axis as an 'eat me' signal for Kupffer cells.


Assuntos
Citofagocitose , Células de Kupffer , Humanos , Fagocitose/genética , Galectinas/genética , Galectinas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
2.
Brief Bioinform ; 25(4)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38975895

RESUMO

Spatial transcriptomics provides valuable insights into gene expression within the native tissue context, effectively merging molecular data with spatial information to uncover intricate cellular relationships and tissue organizations. In this context, deciphering cellular spatial domains becomes essential for revealing complex cellular dynamics and tissue structures. However, current methods encounter challenges in seamlessly integrating gene expression data with spatial information, resulting in less informative representations of spots and suboptimal accuracy in spatial domain identification. We introduce stCluster, a novel method that integrates graph contrastive learning with multi-task learning to refine informative representations for spatial transcriptomic data, consequently improving spatial domain identification. stCluster first leverages graph contrastive learning technology to obtain discriminative representations capable of recognizing spatially coherent patterns. Through jointly optimizing multiple tasks, stCluster further fine-tunes the representations to be able to capture complex relationships between gene expression and spatial organization. Benchmarked against six state-of-the-art methods, the experimental results reveal its proficiency in accurately identifying complex spatial domains across various datasets and platforms, spanning tissue, organ, and embryo levels. Moreover, stCluster can effectively denoise the spatial gene expression patterns and enhance the spatial trajectory inference. The source code of stCluster is freely available at https://github.com/hannshu/stCluster.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Perfilação da Expressão Gênica/métodos , Biologia Computacional/métodos , Algoritmos , Humanos , Animais , Software , Aprendizado de Máquina
3.
Genet Epidemiol ; 47(2): 121-134, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36490288

RESUMO

The large-scale open access whole-exome sequencing (WES) data of the UK Biobank ~200,000 participants is accelerating a new wave of genetic association studies aiming to identify rare and functional loss-of-function (LoF) variants associated with complex traits and diseases. We proposed to merge the WES genotypes and the genome-wide genotyping (GWAS) genotypes of 167,000 UKB homogeneous European participants into a combined reference panel, and then to impute 241,911 UKB homogeneous European participants who had the GWAS genotypes only. We then used the imputed data to replicate association identified in the discovery WES sample. The average imputation accuracy measure r2 is modest to high for LoF variants at all minor allele frequency intervals: 0.942 at MAF interval (0.01, 0.5), 0.807 at (1.0 × 10-3 , 0.01), 0.805 at (1.0 × 10-4 , 1.0 × 10-3 ), 0.664 at (1.0 × 10-5 , 1.0 × 10-4 ) and 0.410 at (0, 1.0 × 10-5 ). As applications, we studied associations of LoF variants with estimated heel BMD and four lipid traits. In addition to replicating dozens of previously reported genes, we also identified three novel associations, two genes PLIN1 and ANGPTL3 for high-density-lipoprotein cholesterol and one gene PDE3B for triglycerides. Our results highlighted the strength of WES based genotype imputation as well as provided useful imputed data within the UKB cohort.


Assuntos
Bancos de Espécimes Biológicos , Exoma , Humanos , Sequenciamento do Exoma , Genótipo , Frequência do Gene , Reino Unido , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Proteína 3 Semelhante a Angiopoietina
4.
Stroke ; 55(8): 2151-2162, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38946544

RESUMO

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.


Assuntos
AVC Isquêmico , Camundongos Knockout , Neurônios , Receptores Acoplados a Proteínas G , Animais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/agonistas , Camundongos , AVC Isquêmico/metabolismo , Masculino , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Reabilitação do Acidente Vascular Cerebral , Fármacos Neuroprotetores/farmacologia , Camundongos Endogâmicos C57BL
5.
Am J Physiol Lung Cell Mol Physiol ; 327(1): L102-L113, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38501173

RESUMO

We have reported previously that during hypoxia exposure, the expression of mature miR-17∼92 was first upregulated and then downregulated in pulmonary artery smooth muscle cells (PASMC) and in mouse lungs in vitro and in vivo. Here, we investigated the mechanisms regulating this biphasic expression of miR-17∼92 in PASMC in hypoxia. We measured the level of primary miR-17∼92 in PASMC during hypoxia exposure and found that short-term hypoxia exposure (3% O2, 6 h) induced the level of primary miR-17∼92, whereas long-term hypoxia exposure (3% O2, 24 h) decreased its level, suggesting a biphasic regulation of miR-17∼92 expression at the transcriptional level. We found that short-term hypoxia-induced upregulation of miR-17∼92 was hypoxia-inducible factor 1α (HIF1α) and E2F1 dependent. Two HIF1α binding sites on miR-17∼92 promoter were identified. We also found that long-term hypoxia-induced suppression of miR-17∼92 expression could be restored by silencing of p53. Mutation of the p53-binding sites in the miR-17∼92 promoter increased miR-17∼92 promoter activity in both normoxia and hypoxia. Our findings suggest that the biphasic transcriptional regulation of miR-17∼92 during hypoxia is controlled by HIF1/E2F1 and p53 in PASMC: during short-term hypoxia exposure, stabilization of HIF1 and induction of E2F1 induce the transcription of miR-17∼92, whereas during long-term hypoxia exposure, hyperphosphorylation of p53 suppresses the expression of miR-17∼92.NEW & NOTEWORTHY We showed that the biphasic transcriptional regulation of miR-17∼92 during hypoxia is controlled by two distinct mechanisms: during short-term hypoxia exposure, induction of HIF1 and E2F1 upregulates miR-17∼92. Longer hypoxia exposure induces hyperphosphorylation of p53 at ser15, which leads to its binding to miR-17∼92 promoter and inhibition of its expression. Our findings provide novel insights into the spatiotemporal regulation of miR-17∼92 that may play a role in the development of human lung diseases including pulmonary hypertension (PH).


Assuntos
Fator de Transcrição E2F1 , Subunidade alfa do Fator 1 Induzível por Hipóxia , MicroRNAs , Artéria Pulmonar , Proteína Supressora de Tumor p53 , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fosforilação , Humanos , Animais , Fator de Transcrição E2F1/metabolismo , Fator de Transcrição E2F1/genética , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Transcrição Gênica , Hipóxia Celular/genética , Miócitos de Músculo Liso/metabolismo , Regiões Promotoras Genéticas/genética , Camundongos , Hipóxia/metabolismo , Hipóxia/genética , Serina/metabolismo , Regulação da Expressão Gênica , Células Cultivadas
6.
Plant Cell Environ ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38752440

RESUMO

C4 NAD-malic enzyme (NAD-ME) species occurs in drier regions and exhibit different drought responses compared to C4 NADP-malic enzyme (NADP-ME) species. However, a physiological mechanism explaining the geographical discrepancies remains uncertain. This study examined gas exchange patterns that might explain different distributions observed between two subtypes of C4 photosynthesis. We measured the response of leaf gas exchange to vapour pressure deficit (VPD) and CO2 in plants from six distinct C4 clades having closely related NAD-ME and NADP-ME species using a Li-Cor 6400 gas exchange system. We found that NAD-ME species exhibited greater relative reductions in stomatal conductance with increases in VPD than NADP-ME species but observed no consistent subtype differences in C4 cycle activity as indicated by the initial slope of the A response to intercellular CO2 concentration. Based on these results, we hypothesise the greater response of gs to increasing VPD may enable NAD-ME plants to outperform NADP-ME plants in hot, dry environments where VPD is normally high.

7.
Cell Mol Neurobiol ; 44(1): 50, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856921

RESUMO

In recent years, spatial transcriptomics (ST) research has become a popular field of study and has shown great potential in medicine. However, there are few bibliometric analyses in this field. Thus, in this study, we aimed to find and analyze the frontiers and trends of this medical research field based on the available literature. A computerized search was applied to the WoSCC (Web of Science Core Collection) Database for literature published from 2006 to 2023. Complete records of all literature and cited references were extracted and screened. The bibliometric analysis and visualization were performed using CiteSpace, VOSviewer, Bibliometrix R Package software, and Scimago Graphica. A total of 1467 papers and reviews were included. The analysis revealed that the ST publication and citation results have shown a rapid upward trend over the last 3 years. Nature Communications and Nature were the most productive and most co-cited journals, respectively. In the comprehensive global collaborative network, the United States is the country with the most organizations and publications, followed closely by China and the United Kingdom. The author Joakim Lundeberg published the most cited paper, while Patrik L. Ståhl ranked first among co-cited authors. The hot topics in ST are tissue recognition, cancer, heterogeneity, immunotherapy, differentiation, and models. ST technologies have greatly contributed to in-depth research in medical fields such as oncology and neuroscience, opening up new possibilities for the diagnosis and treatment of diseases. Moreover, artificial intelligence and big data drive additional development in ST fields.


Assuntos
Bibliometria , Transcriptoma , Humanos , Transcriptoma/genética , Publicações , Animais
8.
Langmuir ; 40(20): 10759-10768, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38712734

RESUMO

Bouncing dynamics of a trailing drop off-center impacting a leading drop with varying time intervals and Weber numbers are investigated experimentally. Whether the trailing drop impacts during the spreading or receding process of the leading drop is determined by the time interval. For a short time interval of 0.15 ≤ Δt* ≤ 0.66, the trailing drop impacts during the spreading of the leading drop, and the drops completely coalesce and rebound; for a large time interval of 0.66 < Δt* ≤ 2.21, the trailing drop impacts during the receding process, and the drops partially coalesce and rebound. Whether the trailing drop directly impacts the surface or the liquid film of the leading drop is determined by the Weber number. The trailing drop impacts the surface directly at moderate Weber numbers of 16.22 ≤ We ≤ 45.42, while it impacts the liquid film at large Weber numbers of 45.42 < We ≤ 64.88. Intriguingly, when the trailing drop impacts the surface directly or the receding liquid film, the contact time increases linearly with the time interval but independent of the Weber number; when the trailing drop impacts the spreading liquid film, the contact time suddenly increases, showing that the force of the liquid film of the leading drop inhibits the receding of the trailing drop. Finally, a theoretical model of the contact time for the drops is established, which is suitable for different impact scenarios of the successive off-center impact. This study provides a quantitative relationship to calculate the contact time of drops successively impacting a superhydrophobic surface, facilitating the design of anti-icing surfaces.

9.
World J Urol ; 42(1): 278, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691246

RESUMO

PURPOSE: This study is centered on the critical role of anterior fibromuscular stroma (AFS) preservation in prostate enucleation, an emerging strategy aimed at minimizing postoperative urinary incontinence-a common concern in benign prostatic hyperplasia (BPH) surgeries. By focusing on postoperative voiding volumes (VV), our research investigates the efficacy of AFS preservation. This approach, distinct in its methodology, is hypothesized to improve urinary function post-surgery, thereby offering a potentially significant advancement in BPH surgical treatments. MATERIALS AND METHODS: A retrospective analysis was conducted, comparing patients who underwent prostate enucleation in 2017 without intentional AFS preservation to those in 2019 with this technique. We examined variables including age, BMI, diabetes, hypertension, and preoperative VV to assess their effect on post-catheter removal VV. The study's methodology includes a thorough review of the primary statistical analysis methods employed. RESULTS: Our analysis indicates that while the 2017 and 2019 cohorts were similar in most preoperative parameters, the 2019 group that underwent AFS-preserved surgery showed a significant improvement in postoperative VVs. This was less pronounced in the patient group aged over 70, underscoring the importance of this demographic in our study. CONCLUSIONS: The study concludes that intentional preservation of AFS during prostate enucleation positively impacts early postoperative VVs, with limited improvement in older patients. These findings highlight the potential of AFS preservation not only in enhancing urinary outcomes post-surgery but also in shaping future BPH surgical procedures and research directions.


Assuntos
Complicações Pós-Operatórias , Próstata , Prostatectomia , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/cirurgia , Estudos Retrospectivos , Idoso , Prostatectomia/métodos , Pessoa de Meia-Idade , Próstata/cirurgia , Fatores Etários , Complicações Pós-Operatórias/prevenção & controle , Tratamentos com Preservação do Órgão/métodos , Micção/fisiologia
10.
World J Urol ; 42(1): 305, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724829

RESUMO

PURPOSE: Postoperative urinary retention (PUR) is a common complication after prostate enucleation, which leads to an increased length of hospital stay and decreased postoperative satisfaction. This study determined the predictive factors of postoperative urine retention within 1 month after prostate enucleation and investigated whether PUR influences surgical outcomes at the 2-week, 3-month, and 6-month follow-up time points. METHODS: Data were collected from the electronic medical records of 191 patients with benign prostatic obstruction (BPO) during October 2018 to September 2021. Of them, 180 patients who underwent thulium laser or plasma kinetic enucleation of the prostate (ThuLEP, PKEP) were separated into the PUR group (n = 24) and the non-PUR (NPUR) group (n = 156). Uroflowmetry and the International Prostate Symptom Score (IPSS) questionnaire were followed up at 2 weeks, 3 months, and 6 months postoperatively. RESULTS: The PUR group had a significantly higher percentage of patients with type 2 diabetes mellitus (DM) than the NPUR group. Postoperatively, compared with the NPUR group, the PUR group had significantly less improvement in changes in the IPSS Quality of Life scores at 2 weeks, the total IPSS(International Prostate Symptom Score) at all follow-up times, the IPSS-S(IPSS storage subscores) at 2 weeks and 3 months, and the IPSS-V(IPSS voiding subscores) at all follow-up times. Predictive factors for PUR include lower preoperative maximum urinary flow (Qmax), lower preoperative total IPSS, and higher operation time. CONCLUSION: Lower preoperative Qmax, lower IPSS scores, and longer operation time were risk factors for PUR. Furthermore, PUR could be a prognostic factor for prostatic enucleation surgical outcomes.


Assuntos
Complicações Pós-Operatórias , Prostatectomia , Hiperplasia Prostática , Retenção Urinária , Humanos , Masculino , Retenção Urinária/etiologia , Retenção Urinária/epidemiologia , Hiperplasia Prostática/cirurgia , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade , Prostatectomia/métodos , Prostatectomia/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos , Endoscopia
11.
Diabetes Obes Metab ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030922

RESUMO

AIM: Glucagon-like peptide 1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are both recommended for patients with diabetes, yet their effects on the development or progression of diabetic retinopathy (DR) are largely unknown. METHODS: In this retrospective cohort study, data were collected from a nationwide database. Patients with diabetes who initiated treatment with a GLP1RA or SGLT2i between 1 May 2016 and 31 December 2017, were identified. Patients were divided into those with or without a previous diagnosis of DR and then categorized into the GLP1RA and the SGLT2i groups according to drug use. The primary outcome of interest in the DR group was the composite of new-onset proliferative DR, vitreous haemorrhage and tractional retinal detachment (RD). In the non-DR group, the primary outcome was the composite of newly diagnosed DR of any severity, vitreous haemorrhage and RD. RESULTS: In total, 97 413 patients were identified. After matching, 1517 patients were treated with a GLP1RA and 3034 with an SGLT2i in the DR cohort. In the non-DR cohort, 9549 initiated a GLP1RA and 19 098 initiated an SGLT2i. In patients with pre-existing DR, the incidence of any DR progression event was significantly higher in the GLP1RA group than the SGLT2i group (subdistribution hazard ratio 1.50, 95% confidence interval 1.01-2.23), primarily because of the increased risk of tractional RD. In patients without DR at baseline, the risks of all ocular outcomes were similar between the GLP1RA and SGLT2i groups. CONCLUSIONS: In patients with diabetes mellitus and established DR, GLP1RA treatment was associated with increased risks of DR progression compared with SGLT2i use.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38754724

RESUMO

OBJECTIVE: Patients with symptomatic lower extremity arterial disease (LEAD) are recommended to receive antiplatelet therapy, while direct oral anticoagulants (DOACs) are standard for stroke prevention in patients with atrial fibrillation (AF). For patients with concomitant LEAD and AF, data comparing dual antithrombotic therapy (an antiplatelet agent used in conjunction with a DOAC) vs. DOAC monotherapy are scarce. This retrospective cohort study, based on data from the Taiwan National Health Insurance Research Database, aimed to compare the efficacy and safety of these antithrombotic strategies. METHODS: Patients with AF who underwent revascularisation for LEAD between 2012 - 2020 and received any DOAC within 30 days of discharge were included. Patients were grouped by antiplatelet agent exposure into the dual antithrombotic therapy and DOAC monotherapy groups. Inverse probability of treatment weighting was used to mitigate selection bias. Major adverse limb events (MALEs), ischaemic stroke or systemic embolism, and bleeding outcomes were compared. Patients were followed until the occurrence of any study outcome, death, or up to two years. RESULTS: A total of 1 470 patients were identified, with 736 in the dual antithrombotic therapy group and 734 in the DOAC monotherapy group. Among them, 1 346 patients received endovascular therapy as the index revascularisation procedure and 124 underwent bypass surgery. At two years, dual antithrombotic therapy was associated with a higher risk of MALEs than DOAC monotherapy (subdistribution hazard ratio [SHR] 1.34, 95% confidence interval [CI] 1.15 - 1.56), primarily driven by increased repeat revascularisation. Dual antithrombotic therapy was also associated with a higher risk of major bleeding (SHR 1.43, 95% CI 1.05 - 1.94) and gastrointestinal bleeding (SHR 2.17, 95% CI 1.42 - 3.33) than DOAC monotherapy. CONCLUSION: In patients with concomitant LEAD and AF who underwent peripheral revascularisation, DOAC monotherapy was associated with a lower risk of MALEs and bleeding events than dual antithrombotic therapy.

13.
Int J Legal Med ; 138(2): 561-570, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37801116

RESUMO

Species identification of biological specimens can provide the valuable clues and accelerate the speed of prosecution material processing for forensic investigation, especially when the case scene is inaccessible and the physical evidence is cumbersome. Thus, establishing a rapid, simple, and field-adapted species identification method is crucial for forensic scientists, particularly as first-line technology at the crime scene for initial rapid screening. In this study, we established a new field-adapted species identification method by combining multiplex multienzyme isothermal rapid amplification (MIRA), lateral flow dipstick (LFD) system, and universal primers. Universal primers targeting COX I and COX II genes were used in multiplex MIRA-LFD system for seven species identification, and a dedicated MIRA-LFD system primer targeting CYT B gene was used to detect the human material. DNA extraction was performed by collecting DNA directly from the centrifuged supernatant. Our study found that the entire amplification process took only 15 min at 37 °C and the results of LFDs could be visually observed after 10 min. The detection sensitivity of human material could reach 10 pg, which is equivalent to the detection of single cell. Different common animal samples mixed at the ratio of 1 ng:1 ng, 10 ng:1 ng, and 1 ng:10 ng could be detected successfully. Furthermore, the damaged and degraded samples could also be detected. Therefore, the convenient, feasible, and rapid approach for species identification is suitable for popularization as first-line technology at the crime scene for initial rapid screening and provides a great convenient for forensic application.


Assuntos
DNA , Técnicas de Amplificação de Ácido Nucleico , Animais , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Sensibilidade e Especificidade , Primers do DNA/genética , Reação em Cadeia da Polimerase/métodos
14.
Int J Legal Med ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38858273

RESUMO

Monozygotic (MZ) twins cannot be distinguished using conventional forensic STR typing because they present identical STR genotypings. However, MZ twins do not always live in the same environment and often have different dietary and other lifestyle habits. Metabolic profiles are deyermined by individual characteristics and are also influenced by the environment in which they live. Therefore, they are potential markers capable of identifying MZ twins. Moreover, the production of proteins varies from organism to organism and is influenced by both the physiological state of the body and the external environment. Hence, we used metabolomics and proteomics to identify metabolites and proteins in peripheral blood to discriminate MZ twins. We identified 1749 known metabolites and 622 proteins in proteomic analysis. The metabolic profiles of four pairs of MZ twins revealed minor differences in intra-MZ twins and major differences in inter-MZ twins. Each pair of MZ twins exhibited distinct characteristics, and four metabolites-methyl picolinate, acesulfame, paraxanthine, and phenylbenzimidazole sulfonic acid-were observed in all four MZ twin pairs. These four differential exogenous metabolites conincidently show that the different external environments and life styles can be well distinguished by metabolites, considering that twins do not all have the same eating habits and living environments. Moreover, MZ twins showed different protein profiles in serum but not in whole blood. Thus, our results indicate that differential metabolites provide potential biomarkers for the personal identification of MZ twins in forensic medicine.

15.
Acta Pharmacol Sin ; 45(6): 1287-1304, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38360930

RESUMO

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.


Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Humanos , Feminino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologia , Farmacologia em Rede , Modelos Biológicos , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Camundongos , Linhagem Celular Tumoral , Metástase Neoplásica
16.
Urol Int ; : 1-7, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740009

RESUMO

INTRODUCTION: Benign prostatic enlargement (BPE) and lower urinary tract symptoms present challenges in aging men, often addressed through transurethral resection of the prostate (TURP). Despite technological advancements, bladder neck contracture (BNC) remains a concern. This study explores predictors, including comorbidities, influencing BNC after TURP. METHODS: A retrospective cohort study at Changhua Christian Hospital analyzed 2041 BPE patients undergoing bipolar TURP. Preoperative urinary catheterization and resection speed were categorized. Patient data included demographics, comorbidities, operative details, and outcomes. Statistical analyses utilized χ2, Kruskal-Wallis tests, and Cox regression models. RESULTS: Within 3 years, 306 (15%) patients developed BNC. Univariate Cox regression identified chronic heart failure (p = 0.033), chronic obstructive pulmonary disease (COPD; p = 0.002), preoperative urinary catheterization (p < 0.001), and low resection speed (p = 0.045) as significant BNC risk factors. Notably, COPD (p = 0.011) and preoperative urinary catheterization (p < 0.001) emerged as independent risk factors for BNC development in multivariate Cox regression analysis. CONCLUSIONS: Preoperative urinary catheterization and COPD were significant predictors of BNC post-TURP, while resection speed showed no significant influence. These findings offer clinicians insights for risk assessment, enhancing patient outcomes, and optimizing resources post-TURP.

17.
Endocr Res ; : 1-10, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869186

RESUMO

Thyroid Eye Disease (TED) is an inflammatory autoimmune condition affecting the eyes, often associated with Graves' disease. Inflammation is important in TED, involving immune cells and orbital tissues. While inflammatory markers have been studied in other diseases, their role in TED is unclear. We included 734 participants from 5 eligible studies investigated associations between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) and TED. Initial analysis found no significant differences in these markers between TED and control groups. However, sensitivity analysis excluding an outlier study revealed significant differences in NLR, PLR, and MLR between groups, suggesting the potential association between these inflammatory markers and TED. More research is needed, but these findings indicate complex TED pathogenesis and that inflammation may offer insights for TED diagnosis and management.

18.
Int J Urol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007219

RESUMO

OBJECTIVES: This study aims to evaluate the impact of anterior fibromuscular stroma preserved enucleation (AFSPE) of the prostate on serum testosterone levels in patients with benign prostatic obstruction (BPO) and to explore age-related differences in postoperative testosterone elevation. METHODS: In a retrospective analysis, 304 patients from a pool of 560 who underwent AFSPE at Linkou Chang Gung Memorial Hospital between January 2018 and December 2021 were evaluated. Patients were stratified based on preoperative testosterone levels into low (<3.5 ng/mL) and normal (≥3.5 ng/mL) groups. Serum testosterone levels were measured preoperatively, at 1.5 and 3-6 months postoperatively. Age and other demographic data were analyzed as potential factors influencing testosterone changes. RESULTS: The low-testosterone group (n = 90) showed significant testosterone increases, from an average of 2.61 ng/mL preoperatively to 3.3 ng/mL at 1.5 months and 3.59 ng/mL at 3-6 months postoperatively (p < 0.0001). The normal-testosterone group (n = 214) maintained stable testosterone levels at 1.5 months but exhibited a significant rise to 6.06 ng/mL by 3-6 months (p = 0.0079). Older age was inversely associated with postoperative testosterone elevation in both groups. Improvements in nocturia were notable in both groups. CONCLUSIONS: AFSPE of the prostate significantly elevates serum testosterone levels in men with BPO, particularly benefiting those initially with low levels. Age is a crucial factor influencing postoperative testosterone changes, indicating that younger patients may benefit more from this intervention. AFSPE offers a promising approach for improving hormonal health in BPO patients, alongside alleviating urinary symptoms.

19.
Phytochem Anal ; 35(2): 409-418, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37872850

RESUMO

INTRODUCTION: Panax ginseng and Panax quinquefolium are traditional Chinese herb medicines and similar in morphology and some chemical components but differ in drug properties, so they cannot be mixed. However, the processed products of them are often sold in the form of slices, powder, and capsules, which are difficult to identify by traditional morphological methods. Furthermore, an accurate evaluation of P. ginseng, P. quinquefolium and the processed products have not been conducted. OBJECTIVE: This study aimed to establish a catalysed hairpin assembly (CHA) identification method for authenticating products made from P. ginseng and P. quinquefolium based on single nucleotide polymorphism (SNP) differences. METHOD: By analysing the differences of SNP in internal transcribed spacer 2 (ITS2) in P. ginseng and P. quinquefolium to design CHA-specific hairpins. Establish a sensitive and efficient CHA method that can identify P. ginseng and P. quinquefolium, use the sequencing technology to verify the accuracy of this method in identifying Panax products, and compare this method with high-resolution melting (HRM). RESULTS: The reaction conditions of CHA were as follows: the ratio of forward and reverse primers, 20:1; hairpin concentration, 5 ng/µL. Compared with capillary electrophoresis, this method had good specificity and the limit of detection was 0.5 ng/µL. The result of Panax product identification with CHA method were coincidence with that of the sequencing method; the positive rate of CHA reaction was 100%. CONCLUSION: This research presents an effective identification method for authenticating P. ginseng and P. quinquefolium products, which is helpful to improve the quality of Panax products.


Assuntos
Panax , Panax/genética , Panax/química , Medicina Tradicional Chinesa , Polimorfismo de Nucleotídeo Único , Tecnologia
20.
Int J Nurs Pract ; 30(1): e13155, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37056171

RESUMO

AIMS: This study aims to examine the prevalence of anxiety symptoms and identify predictors of anxiety among pregnant women with gestational diabetes mellitus and their partners and explore the mediating role of marital satisfaction between maternal and paternal anxiety. DESIGN: A cross-sectional study was conducted in Guangzhou, China, from July 2021 to May 2022. METHODS: A total of 306 dyads of pregnant women with gestational diabetes mellitus and their partners completed the State-Trait Anxiety Inventory, Locke-Wallace Marital Adjustment Test and the socio-demographic and clinical data sheet. RESULTS: The prevalence of anxiety symptoms was 32.4% and 36.6% in pregnant women with gestational diabetes mellitus and their partners, respectively. The predictors of maternal anxiety were paternal anxiety, maternal marital satisfaction, maternal monthly salary, fasting glucose value and 1-h glucose value. By contrast, the predictors of paternal anxiety were maternal anxiety, paternal marital satisfaction and paternal monthly salary. Moreover, the relationship between maternal and paternal anxiety was mediated by marital satisfaction. CONCLUSIONS: The anxiety symptoms of pregnant women with gestational diabetes mellitus and their partners influence each other, and this relationship was mediated by marital satisfaction. Every couple should be screened for anxiety symptoms and treated as a team rather than focusing solely on the pregnant woman.


Assuntos
Diabetes Gestacional , Gestantes , Masculino , Gravidez , Feminino , Humanos , Diabetes Gestacional/epidemiologia , Estudos Transversais , Ansiedade/epidemiologia , Glucose , Satisfação Pessoal
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