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1.
Microbiome ; 12(1): 166, 2024 Sep 07.
Article de Anglais | MEDLINE | ID: mdl-39244624

RÉSUMÉ

BACKGROUND: Microbial anaerobic metabolism is a key driver of biogeochemical cycles, influencing ecosystem function and health of both natural and engineered environments. However, the temporal dynamics of the intricate interactions between microorganisms and the organic metabolites are still poorly understood. Leveraging metagenomic and metabolomic approaches, we unveiled the principles governing microbial metabolism during a 96-day anaerobic bioreactor experiment. RESULTS: During the turnover and assembly of metabolites, homogeneous selection was predominant, peaking at 84.05% on day 12. Consistent dynamic coordination between microbes and metabolites was observed regarding their composition and assembly processes. Our findings suggested that microbes drove deterministic metabolite turnover, leading to consistent molecular conversions across parallel reactors. Moreover, due to the more favorable thermodynamics of N-containing organic biotransformations, microbes preferentially carried out sequential degradations from N-containing to S-containing compounds. Similarly, the metabolic strategy of C18 lipid-like molecules could switch from synthesis to degradation due to nutrient exhaustion and thermodynamical disadvantage. This indicated that community biotransformation thermodynamics emerged as a key regulator of both catabolic and synthetic metabolisms, shaping metabolic strategy shifts at the community level. Furthermore, the co-occurrence network of microbes-metabolites was structured around microbial metabolic functions centered on methanogenesis, with CH4 as a network hub, connecting with 62.15% of total nodes as 1st and 2nd neighbors. Microbes aggregate molecules with different molecular traits and are modularized depending on their metabolic abilities. They established increasingly positive relationships with high-molecular-weight molecules, facilitating resource acquisition and energy utilization. This metabolic complementarity and substance exchange further underscored the cooperative nature of microbial interactions. CONCLUSIONS: All results revealed three key rules governing microbial anaerobic degradation. These rules indicate that microbes adapt to environmental conditions according to their community-level metabolic trade-offs and synergistic metabolic functions, further driving the deterministic dynamics of molecular composition. This research offers valuable insights for enhancing the prediction and regulation of microbial activities and carbon flow in anaerobic environments. Video Abstract.


Sujet(s)
Dépollution biologique de l'environnement , Bioréacteurs , Métabolomique , Microbiote , Anaérobiose , Bioréacteurs/microbiologie , Bactéries/métabolisme , Bactéries/génétique , Bactéries/classification , Métagénomique , Méthane/métabolisme , Thermodynamique , Multi-omique
2.
Am J Cancer Res ; 14(7): 3523-3532, 2024.
Article de Anglais | MEDLINE | ID: mdl-39113858

RÉSUMÉ

Various first-line gemcitabine-based or fluorouracil-based combination regimens were approved in patients with advanced pancreatic cancer. Recent randomized clinical trials (RCTs) have investigated chemotherapy backbones in combination with novel investigational drugs, including chemotherapy agents or targeted drugs. However, the comparative efficacy of these different combination therapies remains limited. This systematic review and network meta-analysis aimed to assess the efficacy of first-line combination therapies for advanced pancreatic cancer. The study included 46 RCTs with 10,499 patients and 47 distinct regimens, using data sources from MEDLINE, EMBASE, Cochrane Clinical Trials, and ClinicalTrials.gov from January 1, 2010 to April 23, 2024. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included overall response rate (ORR) and disease control rate (DCR). The analysis revealed that gemcitabine+nab-paclitaxel (GA), GA with platinum and fluorouracil (GA+Plat+FU), gemcitabine with fluorouracil (G+FU), G+Plt+FU, and FOLFIRINOX were associated with superior OS and PFS compared to gemcitabine monotherapy. Triplet or quadruplet polychemotherapy combinations, such as GA+Plat+FU, G+Plt+FU, and FOLFIRINOX, demonstrated better OS benefit with hazard ratios of 0.42 (95% CI, 0.26-0.68), 0.41 (95% CI, 0.24-0.71), and 0.58 (95% CI, 0.48-0.71), respectively, compared to doublet regimens like GA and G+FU, which had hazard ratios of 0.70 (95% CI, 0.59-0.82) and 0.82 (95% CI, 0.72-0.95), respectively. Notably, no targeted drugs, monoclonal antibodies, or other medications showed improved survival when added to chemotherapy backbones. These findings support the use of gemcitabine-based or fluorouracil-based triplet or quadruplet regimens for better survival outcomes in patients with advanced pancreatic cancer. Further research is warranted to explore the potential benefits of adding chemotherapy agents, such as fluorouracil, to the GA doublet regimen.

3.
Opt Lett ; 49(17): 4895-4898, 2024 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-39207991

RÉSUMÉ

A method for maintaining a fixed phase relationship between the driving signal of acousto-optic modulator (AOM) and the original mode-locked seed laser is proposed and realized, which stabilizes the amplitude of diffracted signal output from the AOM for subsequent amplification. A field-programmable gate array (FPGA), combined with external summing amplifiers, is used to directly synthesize high-timing-precision driving signals that are synchronized with the seed laser pulses, and the accuracy of signal timing control reaches 160 ps. Using this driver, the standard deviation of the diffracted signal output from the AOM is significantly decreased from 0.52% to 0.18%. This pulse-picking solution also includes a control system that can flexibly control the frequency, gating width, etc., of the driving signal, which makes it more convenient for subsequent laser amplification and makes it suitable for a variety of mode-locked lasers.

4.
J Clin Immunol ; 44(8): 176, 2024 Aug 12.
Article de Anglais | MEDLINE | ID: mdl-39133333

RÉSUMÉ

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. CONCLUSION: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.


Sujet(s)
Autoanticorps , Facteur de stimulation des colonies de granulocytes et de macrophages , Infections à Nocardia , Humains , Autoanticorps/immunologie , Autoanticorps/sang , Facteur de stimulation des colonies de granulocytes et de macrophages/immunologie , Infections à Nocardia/immunologie , Infections à Nocardia/diagnostic , Femelle , Mâle , Adulte d'âge moyen , Sujet âgé , Adulte , Protéinose alvéolaire pulmonaire/immunologie , Protéinose alvéolaire pulmonaire/diagnostic , Cryptococcus gattii/immunologie
5.
Small ; : e2312004, 2024 Aug 29.
Article de Anglais | MEDLINE | ID: mdl-39206612

RÉSUMÉ

Thermochromic vanadium dioxide (VO2) can intelligently modulate the transmittance of indoor solar radiation to reduce the energy consumption of air conditioning in buildings. Nevertheless, it remains a great challenge to simultaneously improve the luminous transmittance (Tlum) and solar modulation ability (ΔTsol) of VO2. In this study, a novel approach is employed utilizing a coordination compound to finely tune the growth of a VO2 based composite film, yielding a hierarchical film comprising Zn2V2O7 nanoflakes and VO2@Zn2V2O7 core-shell nanoparticles. Remarkably, the resulting composite films showcase exceptional optical performance, achieving a Tlum of up to 73.0% and ΔTsol of 15.7%. These outcomes are attributed to the antireflection properties inherent in the nanoflake structure and the localized surface plasmon resonance of well-dispersed VO2 nanoparticles. In addition, the Zn2V2O7-VO2 film demonstrates remarkable environmental durability, retaining 90% of its initial ΔTsol even after undergoing aging at 100 °C under 50% relative humidity for a substantial period of 30 days - a durability equivalent to ≈20 years under ambient conditions. This work not only achieves a harmonious balance between Tlum and ΔTsol but also introduces a promising avenue for the design of distinctive composite nanostructures.

6.
J Clin Immunol ; 44(8): 184, 2024 Aug 23.
Article de Anglais | MEDLINE | ID: mdl-39177867

RÉSUMÉ

PURPOSE: Heterozygous STAT1 Gain-of-Function (GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC) among Inborn Errors of Immunity. Clinically, these mutations manifest as a broad spectrum of immune dysregulation, including autoimmune diseases, vascular disorders, and malignancies. The pathogenic mechanisms of immune dysregulation and its impact on immune cells are not yet fully understood. In treatment, JAK inhibitors have shown therapeutic effectiveness in some patients. METHODS: We analyzed clinical presentations, cellular phenotypes, and functional impacts in five Taiwanese patients with STAT1 GOF. RESULTS: We identified two novel GOF mutations in 5 patients from 2 Taiwanese families, presenting with symptoms of CMC, late-onset rosacea, and autoimmunity. The enhanced phosphorylation and delayed dephosphorylation were displayed by the patients' cells. There are alterations in both innate and adaptive immune cells, including expansion of CD38+HLADR +CD8+ T cells, a skewed activated Tfh cells toward Th1, reduction of memory, marginal zone and anergic B cells, all main functional dendritic cell lineages, and a reduction in classical monocyte. Baricitinib showed therapeutic effectiveness without side effects. CONCLUSION: Our study provides the first comprehensive clinical and molecular characteristics in STAT1 GOF patient in Taiwan and highlights the dysregulated T and B cells subsets which may hinge the autoimmunity in STAT1 GOF patients. It also demonstrated the therapeutic safety and efficacy of baricitinib in pediatric patient. Further research is needed to delineate how the aberrant STAT1 signaling lead to the changes in cellular populations as well as to better link to the clinical manifestations of the disease.


Sujet(s)
Candidose mucocutanée chronique , Mutation gain de fonction , Immunophénotypage , Pyrazoles , Facteur de transcription STAT-1 , Humains , Facteur de transcription STAT-1/génétique , Facteur de transcription STAT-1/métabolisme , Candidose mucocutanée chronique/génétique , Candidose mucocutanée chronique/diagnostic , Candidose mucocutanée chronique/thérapie , Mâle , Femelle , Pyrazoles/usage thérapeutique , Sulfonamides/usage thérapeutique , Azétidines/usage thérapeutique , Purines/usage thérapeutique , Enfant , Adolescent , Taïwan , Adulte
7.
J Clin Med ; 13(14)2024 Jul 16.
Article de Anglais | MEDLINE | ID: mdl-39064190

RÉSUMÉ

Background: For patients with obstructive jaundice and who are indicated for pancreaticoduodenectomy (PD) or biliary intervention, either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography and drainage (PTCD) may be indicated preoperatively. However, the possibility of procedure-related postoperative biliary tract infection (BTI) should be a concern. We tried to evaluate the impact of ERCP and PTCD on postoperative BTI. Methods: Patients diagnosed from June 2013 to March 2022 with periampullary lesions and with PD indicated were enrolled in this cohort. Patients without intraoperative bile culture and non-neoplastic lesions were excluded. Clinical information, including demographic and laboratory data, pathologic diagnosis, results of microbiologic tests, and relevant infectious outcomes, was extracted from medical records for analysis. Results: One-hundred-and-sixty-four patients from the cohort (164/689) underwent preoperative biliary intervention, either ERCP (n = 125) or PTCD (n = 39). The positive yield of intraoperative biliary culture was significantly higher in patients who underwent ERCP than in PTCD (90.4% vs. 41.0%, p < 0.001). Although there was no significance, a trend of higher postoperative BTI (13.8% vs. 2.7%) and BTI-related septic shock (5 vs. 0, 4.0% vs. 0%) in the ERCP group was noticed. While the risk factors for postoperative BTI have not been confirmed, a trend suggesting a higher incidence of BTI associated with ERCP procedures was observed, with a borderline p-value (p = 0.05, regarding ERCP biopsy). Conclusions: ERCP in patients undergoing PD increases the positive yield of intraoperative biliary culture. PTCD may be the favorable option if preoperative biliary intervention is indicated.

8.
Biomolecules ; 14(7)2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-39062469

RÉSUMÉ

Radiotherapy is an important treatment for many unresectable advanced malignant tumors, and radiotherapy-associated inflammatory reactions to radiation and other toxic side effects are significant reasons which reduce the quality of life and survival of patients. FLASH-radiotherapy (FLASH-RT), a prominent topic in recent radiation therapy research, is an ultra-high dose rate treatment known for significantly reducing therapy time while effectively targeting tumors. This approach minimizes radiation side effects on at-risk organs and maximally protects surrounding healthy tissues. Despite decades of preclinical exploration and some notable achievements, the mechanisms behind FLASH effects remain debated. Standardization is still required for the type of FLASH-RT rays and dose patterns. This review addresses the current state of FLASH-RT research, summarizing the biological mechanisms behind the FLASH effect. Additionally, it examines the impact of FLASH-RT on immune cells, cytokines, and the tumor immune microenvironment. Lastly, this review will discuss beam characteristics, potential clinical applications, and the relevance and applicability of FLASH-RT in treating advanced cancers.


Sujet(s)
Tumeurs , Microenvironnement tumoral , Humains , Tumeurs/radiothérapie , Microenvironnement tumoral/effets des radiations , Animaux , Radiothérapie/méthodes , Radiothérapie/effets indésirables , Cytokines/métabolisme
9.
Pract Radiat Oncol ; 2024 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-39019209

RÉSUMÉ

Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiation therapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by 3 cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques such as magnetic resonance imaging guided SBRT, and SBRT response assessment.

10.
Phytother Res ; 2024 Jul 22.
Article de Anglais | MEDLINE | ID: mdl-39038923

RÉSUMÉ

Tubular injury and oxidative stress are involved in the pathogenesis of diabetic kidney disease (DKD). Astragaloside IV (ASIV) is a natural antioxidant. The effects and underlying molecular mechanisms of ASIV on DKD have not been elucidated. The db/db mice and high-glucose-stimulated HK2 cells were used to evaluate the beneficial effects of ASIV in vivo and in vitro. Succinylated proteomics was used to identify novel mechanisms of ASIV against DKD and experimentally further validated. ASIV alleviated renal dysfunction and proteinuria, downregulated fasting blood glucose, and upregulated insulin sensitivity in db/db mice. Meanwhile, ASIV alleviated tubular injury, oxidative stress, and mitochondrial dysfunction in vivo and in vitro. Mechanistically, ASIV reversed downregulated 17beta-hydroxysteroid dehydrogenase type 10 (HSD17B10) lysine succinylation by restoring carnitine palmitoyl-transferase1alpha (Cpt1a or CPT1A) activity in vivo and in vitro. Molecular docking and cell thermal shift assay revealed that ASIV may bind to CPT1A. Molecular dynamics simulations demonstrated K99 succinylation of HSD17B10 maintained mitochondrial RNA ribonuclease P (RNase P) stability. The K99R mutation of HSD17B10 induced oxidative stress and disrupted its binding to CPT1A or mitochondrial ribonuclease P protein 1 (MRPP1). Importantly, ASIV restored the interaction between HSD17B10 and MRPP1 in vivo and in vitro. We also demonstrated that ASIV reversed high-glucose-induced impaired RNase P activity in HK2 cells, which was suppressed upon K99R mutation of HSD17B10. These findings suggest that ASIV ameliorates oxidative stress-associated proximal tubular injury by upregulating CPT1A-mediated K99 succinylation of HSD17B10 to maintain RNase P activity.

11.
Biotechnol Lett ; 2024 Jul 17.
Article de Anglais | MEDLINE | ID: mdl-39017763

RÉSUMÉ

Pentachlorophenol (PCP) was once used as a pesticide, germicide, and preservative due to its stable properties and resistance to degradation. This study aimed to design a biosensor for the quantitative and prompt detection of capable of PCP. A cell-free fluorescence biosensor was developed while employing NalC, an allosteric Transcription Factor responsive to PCP and In Vitro Transcription. By adding a DNA template and PCP and employing Electrophoretic Mobility Shift Assay while monitoring the dynamic fluorescence changes in RNA, this study offers evidence of NalC's potential applicability in sensor systems developed for the specific detection of PCP. The biosensor showed the capability for the quantitative detection of PCP, with a Limit of Detection (LOD) of 0.21 µM. Following the addition of Nucleic Acid Sequence-Based Amplification, the fluorescence intensity of RNA revealed an excellent linear relationship with the concentration of PCP, showing a correlation coefficient (R2) of 0.9595. The final LOD was determined to be 0.002 µM. This study has successfully translated the determination of PCP into a fluorescent RNA output, thereby presenting a novel approach for detecting PCP within environmental settings.

12.
Arch Med Sci ; 20(3): 863-875, 2024.
Article de Anglais | MEDLINE | ID: mdl-39050167

RÉSUMÉ

Introduction: Accumulating evidence has proved that long non-coding RNAs (lncRNAs) are involved in progression of glioma. Nevertheless, the role of TUBA4B in glioma remains unclear. Material and methods: The expression of the target gene was measured by quantitative RT-PCR. The prognostic role of TUBA4B was analyzed by Meier survival analysis. Cell proliferation, colony formation, apoptosis, cell cycle, migration and invasion were detected by MTS, soft agar colony forming assay, flow cytometry, and transwell assay. The target interaction of the target gene was validated by the luciferase reporter assay, biotin pull-down assay, and RNA immunoprecipitation. Results: We found that the expression of TUBA4B was lower in glioma tissues and cells. Moreover, patients with a low TUBA4B expression level exhibited poorer prognosis than those with high TUBA4B expression. Meanwhile, ROC analysis revealed that TUBA4B had diagnostic value to distinguish tumor patients from the healthy population. Overexpression of TUBA4B prohibited the malignancy of glioma, such as inhibition of proliferation, decrease of colony formation, arrest of the cell cycle, decline of migration and invasion, and promotion of cell apoptosis. In addition, we found that TUBA4B directly interacted with miR-183 and negatively regulated the expression of miR-183. We also observed that SMAD4 was a downriver target of miR-183 and TUBA4B subsequently exerted its tumor-suppressive effects by coordinating the expression of SMAD4 in glioma. Conclusions: This study revealed for the first time that TUBA4B could be a tumor suppressor gene in glioma by adjustment of the TUBA4B/miR-183/SMAD4 axis, which may provide a useful prognostic biomarker and promising therapeutic target for glioma treatment.

13.
Environ Int ; 190: 108869, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38968831

RÉSUMÉ

Assessing the risk of human pathogens in the environment is crucial for controlling the spread of diseases and safeguarding human health. However, conducting a thorough assessment of low-abundance pathogens in highly complex environmental microbial communities remains challenging. This study compiled a comprehensive catalog of 247 human-pathogenic bacterial taxa from global biosafety agencies and identified more than 78 million genome-specific markers (GSMs) from their 17,470 sequenced genomes. Subsequently, we analyzed these pathogens' types, abundance, and diversity within 474 shotgun metagenomic sequences obtained from diverse environmental sources. The results revealed that among the four habitats studied (air, water, soil, and sediment), the detection rate, diversity, and abundance of detectable pathogens in the air all exceeded those in the other three habitats. Air, sediment, and water environments exhibited identical dominant taxa, indicating that these human pathogens may have unique environmental vectors for their transmission or survival. Furthermore, we observed the impact of human activities on the environmental risk posed by these pathogens, where greater amounts of human activities significantly increased the abundance of human pathogenic bacteria, especially in water and air. These findings have remarkable implications for the environmental risk assessment of human pathogens, providing valuable insights into their presence and distribution across different habitats.


Sujet(s)
Microbiologie de l'air , Bactéries , Microbiologie du sol , Humains , Bactéries/isolement et purification , Bactéries/génétique , Bactéries/classification , Microbiologie de l'eau , Surveillance de l'environnement , Métagénomique , Réservoirs de maladies/microbiologie , Appréciation des risques
14.
Food Res Int ; 188: 114454, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38823832

RÉSUMÉ

The Amadori rearrangement products are an important flavor precursor in the Maillard reaction. Its thermal decomposition products usually contribute good flavors in foods. Therefore, investigating the thermal breakdown of Amadori products is significant for understanding the flavor forming mechanism in the Maillard reaction. In this study, volatiles from thermal decomposition of Amadori products in cysteine and glucose Maillard reaction was investigated by a thermal desorption cryo-trapping system combined with gas chromatography-mass spectrometry (GC-MS). A total of 60 volatiles were detected and identified. Meanwhile, the forming mechanism of 2-methylthiophene, a major decomposition product, was also investigated by using density functional theory. Seventeen reactions, 12 transition states, energy barrier and rate constant of each reaction were finally obtained. Results reveal that it is more likely for Amadori products of cysteine and glucose to undergo decomposition under neutral or weakly alkaline conditions.


Sujet(s)
Cystéine , Chromatographie gazeuse-spectrométrie de masse , Glucose , Réaction de Maillard , Composés organiques volatils , Cystéine/composition chimique , Glucose/composition chimique , Composés organiques volatils/composition chimique , Composés organiques volatils/analyse , Théorie de la fonctionnelle de la densité , Température élevée
15.
J Kidney Cancer VHL ; 11(2): 27-38, 2024.
Article de Anglais | MEDLINE | ID: mdl-38863736

RÉSUMÉ

Metastatic renal cell carcinoma (mRCC) is a heterogenous disease with a variable clinical course. While therapies for treatment of this condition have progressed, they are not without toxicity. In some patients, active surveillance (AS) of this disease is increasingly considered to delay its toxicity. This article seeks to review the literature and discuss management of metastatic renal cell carcinoma, specifically regarding upfront AS, the role of radiation therapy in delaying systemic therapy, and surveillance after initial treatment with systemic therapy. Median time on AS prior to initiation of systemic therapy ranged from 14 to 60 months across studies. AS is appropriate to offer in favorable or intermediate risk, asymptomatic, and systemic treatment naïve patients with mRCC.

16.
Cells ; 13(12)2024 Jun 08.
Article de Anglais | MEDLINE | ID: mdl-38920635

RÉSUMÉ

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications of the conditional reprogramming (CR) cell culture approach, showcasing its capability to rapidly and effectively cultivate patient-derived normal and tumor cells. The CR strategy facilitates the acquisition of stem cell properties by primary cells, precisely recapitulating the human pathophysiology of PCa. This nuanced understanding enables the identification of novel therapeutics. Specifically, our discussion encompasses the utility of CR cells in elucidating PCa initiation and progression, unraveling the molecular pathogenesis of metastatic PCa, addressing health disparities, and advancing personalized medicine. Coupled with the tumor organoid approach and patient-derived xenografts (PDXs), CR cells present a promising avenue for comprehending cancer biology, exploring new treatment modalities, and advancing precision medicine in the context of PCa. These approaches have been used for two NCI initiatives (PDMR: patient-derived model repositories; HCMI: human cancer models initiatives).


Sujet(s)
Reprogrammation cellulaire , Tumeurs de la prostate , Humains , Tumeurs de la prostate/anatomopathologie , Mâle , Reprogrammation cellulaire/génétique , Animaux
17.
Front Immunol ; 15: 1402250, 2024.
Article de Anglais | MEDLINE | ID: mdl-38855107

RÉSUMÉ

Background: This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters. Results: Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05). Conclusion: Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.


Sujet(s)
Angioplastie par ballonnet , Marqueurs biologiques , Hypertension pulmonaire , Embolie pulmonaire , Humains , Mâle , Hypertension pulmonaire/sang , Hypertension pulmonaire/étiologie , Hypertension pulmonaire/thérapie , Femelle , Marqueurs biologiques/sang , Adulte d'âge moyen , Embolie pulmonaire/sang , Embolie pulmonaire/thérapie , Sujet âgé , Protéomique/méthodes , Maladie chronique
18.
Zhongguo Gu Shang ; 37(6): 5385-45, 2024 Jun 25.
Article de Chinois | MEDLINE | ID: mdl-38910374

RÉSUMÉ

OBJECTIVE: To explore clinical effect of manipulation reduction combined with vertebral plasty on osteoporotic compression fractures (OVCFs). METHODS: Totally 61 patients with OVCFs treated from January 2022 to March 2024 were randomly divided into self-made spinal locator positioning with manipulation reduction group (treatment group) and traditional Kirchner positioning group (control group). There were 30 patients in treatment group, including 4 males and 26 females, aged from 61 to 87 years old with an average of (73.61±7.17) years old;body mass index (BMI) ranged from 15.24 to 28.89 kg·m-2 with an average of (23.90±3.20) kg·m-2;bone mineral density T value ranged from -4.90 to -2.50 SD with an avergae of (-3.43±0.75) SD;fracture to operation time was 6.50 (4.00, 10.25) d;10 patients were gradeⅠ, 13 patients were gradeⅡ, and 7 patients were grade Ⅲ according to Genant classification of fracture compression. There were 31 patients in control group, including 7 males and 24 females, aged from 61 to 89 years old with an average of (73.63±8.77) years old;BMI ranged from 18.43 to 27.06 kg·m-2 with an average of (23.67±2.35) kg·m-2;bone mineral density T value ranged from -4.60 to -2.50 SD with an avergae of (-3.30±0.68) SD;fracture to operation time was 6.00 (3.00, 8.00) d;11 patients were gradeⅠ, 9 patients were gradeⅡ, and 11 patients were grade Ⅲ according to Genant classification of fracture compression. The puncture times, X-ray fluoroscopy times and puncture time between two groups were observed and compared. Visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and timed up and go test (TUGT) were observed and compared before operation, 3 d and 1 month after operation. RESULTS: All patients were followed up for 1 to 3 months with an average of (2.10±0.80) months. Puncture times, X-ray fluorosecopy times and puncture time in treatment group were 5.00(4.00, 6.00) times, (29.53±5.89) times and 14.83(12.42, 21.20) min, respectively, while those in control group were 7.00(6.00, 8.00) times, (34.58±5.33) times, 22.19(17.33, 27.01) min, treatment group was better than those of control group (P<0.05). There were no significant differences in preoperative VAS, JOA and TUGT between two groups(P>0.05). VAS, JOA and TUGT in both groups were significantly improved after opeation(P<0.05). On the third day after operation, JOA score of treatment group was 23.00 (20.75, 25.00), which was higher than that of control group 20.00(19.00, 23.00)(P<0.05). TUGT of treatment group was 6.26(5.86, 6.57) s, which was better than that of control group 6.90(6.80, 7.14) s (P<0.05). Bone cement leakage occurred with 1 patient in treatment group and 2 patients in control group. CONCLUSION: The optimal scheme of self-made spinal locators for locating descending verteboplasty combined with traditional Chinese medicine reduction manipulation for OVCF patients could reduce the number of intraoperative puncture times, shorten puncture times and reduce number of X-ray fluoroscopy times, and have advantages over the simple positioning of Kirschn's needle in restoring short-term lumbar function and standing and walking ability of postoperative patients.


Sujet(s)
Fractures par compression , Fractures ostéoporotiques , Fractures du rachis , Vertébroplastie , Humains , Mâle , Femelle , Sujet âgé , Fractures par compression/chirurgie , Adulte d'âge moyen , Fractures ostéoporotiques/chirurgie , Vertébroplastie/méthodes , Sujet âgé de 80 ans ou plus , Fractures du rachis/chirurgie
20.
Adv Sci (Weinh) ; : e2402818, 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38898769

RÉSUMÉ

Stretchable electrodes based on liquid metals (LM) are widely used in human-machine interfacing, wearable bioelectronics, and other emerging technologies. However, realizing the high-precision patterning and mechanical stability remains challenging due to the poor wettability of LM. Herein, a method is reported to fabricate LM-based multilayer solid-liquid electrodes (m-SLE) utilizing electrohydrodynamic (EHD) printed confinement template. In these electrodes, LM self-assembled onto these high-resolution templates, assisted by selective wetting on the electrodeposited Cu layer. This study shows that a m-SLE composed of PDMS/Ag/Cu/EGaIn exhibits line width of ≈20 µm, stretchability of ≈100%, mechanical stability ≈10 000 times (stretch/relaxation cycles), and recyclability. The multi-layer structure of m-SLE enables the adjustability of strain sensing, in which the strain-sensitive Ag part can be used for non-distributed detection in human health monitoring and the strain-insensitive EGaIn part can be used as interconnects. In addition, this study demonstrates that near field communication (NFC) devices and multilayer displays integrated by m-SLEs exhibit stable wireless signal transmission capability and stretchability, suggesting its applicability in creating highly-integrated, large-scale commercial, and recyclable wearable electronics.

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