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1.
MethodsX ; 12: 102797, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38966717

RESUMO

A landslide involves the downward movement of a mass of rock, debris, earth, or soil. Landslides happen when gravitational forces and other types of shear stresses on a slope surpass the shear strength of the materials. Additionally, landslides can be triggered by processes that weaken the shear strength of the slope's material. Shear strength primarily depends on two factors such as frictional strength, which is the resistance to movement between the interacting particles of the slope material, and cohesive strength, which is the bonding between those particles. A landslide is a terrible natural disaster that causes much damage to both human life and the economy. It often occurs in steep mountainous areas or hilly regions, ranging in scale from medium to large. It progresses slowly (20-50 mm/year), but when it occurs, it can move at a speed of 3 m/s. Therefore, early detection or prevention of this disaster is an essential and significant task. This paper developed a method to collect and analyze data, with the purpose of determining the possibility of landslide occurrences to reduce its potential losses.•The proposed method is convenient for users to grasp information of landslide phenomenon.•A machine learning model is applied to forecast landslide phenomenon.•Internet of things (IoT) system is utilized to manage and send a warning text to individual email address and mobile devices.

2.
Sci Rep ; 14(1): 15312, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961191

RESUMO

Nontuberculous mycobacteria (NTM) infection diagnosis remains a challenge due to its overlapping clinical symptoms with tuberculosis (TB), leading to inappropriate treatment. Herein, we employed noninvasive metabolic phenotyping coupled with comprehensive statistical modeling to discover potential biomarkers for the differential diagnosis of NTM infection versus TB. Urine samples from 19 NTM and 35 TB patients were collected, and untargeted metabolomics was performed using rapid liquid chromatography-mass spectrometry. The urine metabolome was analyzed using a combination of univariate and multivariate statistical approaches, incorporating machine learning. Univariate analysis revealed significant alterations in amino acids, especially tryptophan metabolism, in NTM infection compared to TB. Specifically, NTM infection was associated with upregulated levels of methionine but downregulated levels of glutarate, valine, 3-hydroxyanthranilate, and tryptophan. Five machine learning models were used to classify NTM and TB. Notably, the random forest model demonstrated excellent performance [area under the receiver operating characteristic (ROC) curve greater than 0.8] in distinguishing NTM from TB. Six potential biomarkers for NTM infection diagnosis, including methionine, valine, glutarate, 3-hydroxyanthranilate, corticosterone, and indole-3-carboxyaldehyde, were revealed from univariate ROC analysis and machine learning models. Altogether, our study suggested new noninvasive biomarkers and laid a foundation for applying machine learning to NTM differential diagnosis.


Assuntos
Biomarcadores , Aprendizado de Máquina , Metabolômica , Infecções por Mycobacterium não Tuberculosas , Tuberculose , Humanos , Metabolômica/métodos , Masculino , Biomarcadores/urina , Feminino , Pessoa de Meia-Idade , Tuberculose/urina , Tuberculose/diagnóstico , Tuberculose/microbiologia , Tuberculose/metabolismo , Infecções por Mycobacterium não Tuberculosas/urina , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , Idoso , Adulto , Metaboloma , Curva ROC , Diagnóstico Diferencial
3.
Radiol Case Rep ; 19(9): 3820-3823, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38983311

RESUMO

Gross hematuria is one of the most common complications in postrenal transplant patients, accounting for 12% of all renal recipients. The management plan in these cases varies depending on different entities, including infection, renal cell carcinoma, chronic graft rejection, kidney calculus, or recurrence of primary disease. On the other hand, vascular malformation like arteriovenous malformation was less likely to be mentioned due to a lack of consensus in the natural history, pathogenesis, and current management. In this article, we report a 62-year-old man presenting with spontaneous hematuria for a week and 2 days of anuria after 3 years of renal transplantation. Abdominal ultrasound and abdominopelvic computed tomography noted an obstruction of the renal pelvis due to blood clots without signs of vascular injuries. An emergency operation was performed to remove blood clots in the renal pelvis, but after that, hematuria was still recurrence. A digital renal graft subtraction angiography (DSA) revealed an arteriovenous malformation (AVM)in the kidney allograft. This lesion was then successfully selective embolized with glue. Given the high accuracy of DSA, our case highlights the potential role of this imaging modality in diagnosing and treating AVM after failure with other modalities.

4.
Commun Biol ; 7(1): 793, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951146

RESUMO

Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [18F]F-AraG, a mitochondrial metabolic tracer capable of tracking activated lymphocytes and adipocytes simultaneously, we demonstrate, in models of glioblastoma and multiple sclerosis, the correlation between intracerebral immune infiltration and changes in brown- and bone marrow adipose tissue. Significantly, we show initial evidence that a neuroinflammation-adipose tissue link may also exist in humans. This study proposes the concept of an intricate immuno-neuro-adipose circuit, and highlights brown- and bone marrow adipose tissue as an intermediary in the communication between the immune and nervous systems. Understanding the interconnectedness within this circuitry may lead to advancements in the treatment and management of various conditions, including cancer, neurodegenerative diseases and metabolic disorders.


Assuntos
Tecido Adiposo Marrom , Doenças Neuroinflamatórias , Animais , Humanos , Tecido Adiposo Marrom/metabolismo , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Medula Óssea/metabolismo , Camundongos , Masculino , Glioblastoma/patologia , Glioblastoma/imunologia , Glioblastoma/metabolismo , Camundongos Endogâmicos C57BL , Feminino , Esclerose Múltipla/patologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/metabolismo , Esclerose Múltipla/diagnóstico por imagem , Tomografia por Emissão de Pósitrons
5.
Sci Adv ; 10(28): eadn0881, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996027

RESUMO

Epithelial ovarian cancer (EOC) remains one of the most lethal gynecological cancers. Cytokine-induced memory-like (CIML) natural killer (NK) cells have shown promising results in preclinical and early-phase clinical trials. In the current study, CIML NK cells demonstrated superior antitumor responses against a panel of EOC cell lines, increased expression of activation receptors, and up-regulation of genes involved in cell cycle/proliferation and down-regulation of inhibitory/suppressive genes. CIML NK cells transduced with a chimeric antigen receptor (CAR) targeting the membrane-proximal domain of mesothelin (MSLN) further improved the antitumor responses against MSLN-expressing EOC cells and patient-derived xenograft tumor cells. CAR arming of the CIML NK cells subtanstially reduced their dysfunction in patient-derived ascites fluid with transcriptomic changes related to altered metabolism and tonic signaling as potential mechanisms. Lastly, the adoptive transfer of MSLN-CAR CIML NK cells demonstrated remarkable inhibition of tumor growth and prevented metastatic spread in xenograft mice, supporting their potential as an effective therapeutic strategy in EOC.


Assuntos
Células Matadoras Naturais , Mesotelina , Neoplasias Ovarianas , Receptores de Antígenos Quiméricos , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Animais , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Feminino , Camundongos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/terapia , Linhagem Celular Tumoral , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/genética , Imunoterapia Adotiva/métodos , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/imunologia , Carcinoma Epitelial do Ovário/terapia , Memória Imunológica , Domínios Proteicos
6.
Sensors (Basel) ; 24(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39001144

RESUMO

A new axially vibrating sensor based on an audio voice coil transducer and a lead zirconate titanate (PZT) piezoelectric disc microphone was developed as a probe for the measurement of in vitro rheological fluid properties, including curing progress for polymethylmethacrylate (PMMA) mixtures with important uses as bone cement in the field of orthopedics. The measurement of the vibrating axial sensor's acoustic spectra in PMMA undergoing curing can be described by a damped harmonic oscillator formalism and resonant frequency (ca. 180 Hz) shift can be used as an indicator of curing progress, with shifts to the blue by as much as 14 Hz. The resonant frequency peak was measured in 19 different 4.0 g PMMA samples to have a rate of shift of 0.0462 ± 0.00624 Hz·s-1 over a period of 400 s while the PMMA was in a dough state and before the PMMA transitioned to a hard-setting phase. This transition is unambiguously indicated by this sensor technology through the generation of a distinct circa 5 kHz high-Q under-damped ring-down response.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38985315

RESUMO

Bruceines A-L are among the quassinoid representatives found in the medicinal plant Brucea javanica (L.). An overview of their pharmacological activities is still unknown. The given research deals with highlights in their pharmacological result, molecular mechanism of action, synthetic progress, and pharmacokinetics. From previous evidence, bruceine derivatives are potential agents for anticancer treatments, as well as they are appropriate to treat inflammation, diabetes, and parasitic infections, and protect the neurons, kidneys, and lungs. Cytokine inhibitions, oxidative stress responses, and various signaling pathways, such as MAPK (mitogen-activated protein kinase) and NF-κB (nuclear factor-kappa B), have been proposed as the underlying mechanisms of action. Synthetic approaches to synthesize new derivatives with enhancement activities are based on free hydroxyl group modifications. Bruceines seem to be promptly absorbed by both oral and intravenous administrations, but their bioavailability is not high (less than 6%). Pre-clinical and clinical studies to prove their anticancer potential and other activities are urgent. Structural modifications, nano-combinations, and synergistic effects are necessary.

8.
Br J Clin Pharmacol ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992893

RESUMO

AIMS: Trans/transfeminine women are disproportionally affected by HIV. Concerns regarding negative drug-drug interactions (DDIs) between ART drugs and gender-affirming hormone therapy (GAHT), specifically feminizing hormone therapy (FHT), may contribute to the lower ART uptake by trans women with HIV compared with their cis counterparts. The aim of this study is to investigate the bidirectional pharmacokinetic effects of components of FHT regimens (oral oestradiol and androgen-suppressing medications) with the ART regimen (bictegravir/emtricitabine/tenofovir alafenamide [B/F/TAF)]. METHODS: We present a protocol for a three-armed, parallel-group, longitudinal (6-month), DDI study. Group 1 includes 15 3trans women with HIV taking FHT and ART; group 2 includes 15 premenopausal cis women with HIV taking ART; group 3 includes 15 trans women without HIV taking FHT. Women with HIV must be on or switch to B/F/TAF at baseline and be virally suppressed for ≥3 months. Trans women must be taking a stable regimen of ≥2 mg daily oral oestradiol and an anti-androgen (pharmaceutical, and/or surgical, and/or medical) for ≥3 months. Plasma ART drug concentrations will be sampled at Month 2 and compared between groups 1 and 2. Serum oestradiol concentrations will be sampled at baseline and Month 2 visits and compared between groups 1 and 3. The primary outcomes are B/F/TAF pharmacokinetic parameters (Cmin, Cmax and AUC) and oestradiol concentrations (Cmin, C4h, Cmax and AUC) at month 2. DISCUSSION: This study is of global importance as it provides critical information regarding safe coadministration of B/F/TAF and FHT, both of which are life-saving therapies for trans women with HIV.

9.
J Am Coll Emerg Physicians Open ; 5(4): e13237, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39027350

RESUMO

Objectives: While our understanding of coronavirus disease 2019 (COVID-19) has evolved, uncertainty remains regarding utility of previously established pulmonary embolism (PE) screening guidelines in patients with COVID-19. Many studies have investigated the efficacy of D-dimer (DD) screenings for patients with COVID-19 admitted to inpatient services, but few have evaluated patients in the emergency department (ED). The purpose of this study was to investigate utility of DD threshold for PE screening in patients with COVID-19 presenting to the ED. Methods: This was a retrospective, multicenter cohort including patients presenting to three EDs between March 1, 2020 and February 1, 2021 who tested positive for COVID-19 during ED visit or in 60 days prior to presentation and had DD ordered in ED. Patients were grouped by those who underwent computed tomography pulmonary angiogram (CTPA) to evaluate for PE and those who did not, and descriptive statistics were performed. Those who underwent CTPA were further divided into PE-positive and PE-negative groups. The discriminative ability of DD in predicting PE in patients with COVID-19 was analyzed using the receiver operating characteristic (ROC) curve. Results: A total of 570 patients with COVID-19 were included in the study, of which 107 underwent CTPA to evaluate for PE. History of diabetes, elevated glucose, elevated lactate dehydrogenase, elevated white blood cell count, elevated platelets, elevated respiratory rate, and lower temperature were associated with increased risk for PE. Compared to those without PE, patients with PE were significantly more likely to be hospitalized (100% vs. 82%, p = 0.020) and admitted to the ICU (64% vs. 24%, p = 0.002). Those with PE had a significantly higher median DD value (21,177 ng/mL) compared to PE-negative group (952 ng/mL, p < 0.001). The ROC curve for DD in predicting PE had an area under the curve of 0.91 (95% confidence interval [0.84, 0.98]). In our study population, the optimal DD threshold for predicting PE was 1815 ng/mL (sensitivity 93% and specificity 80%). A conservative threshold of 1089 ng/mL could be used with sensitivity 100% and specificity 58%. Conclusion: DD is often elevated in patients with COVID-19, regardless of PE. While the classically used DD cutoff is 500 ng/mL, our study demonstrated a threshold of 1089 ng/mL safely predicted PE in patients with COVID-19 .

10.
World J Mens Health ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39028131

RESUMO

PURPOSE: This study aimed to examine current global practices in regenerative therapy (RT) for erectile dysfunction (ED) and to establish expert recommendations for its use, addressing the current lack of solid evidence and standardized guidelines. MATERIALS AND METHODS: A 39-question survey was developed by senior Global Andrology Forum (GAF) experts to comprehensively cover clinical aspects of RT. This was distributed globally via a secure online Google Form to ED specialists through the GAF website, international professional societies, and social media, the responses were analyzed and presented for frequencies as percentages. Consensus on expert recommendations for RT use was achieved using the Delphi method. RESULTS: Out of 479 respondents from 62 countries, a third reported using RT for ED. The most popular treatment was low-intensity shock wave therapy (54.6%), followed by platelet-rich plasma (24.5%) and their combination (14.7%), with stem cell therapy being the least used (3.7%). The primary indication for RT was the refractory or adverse effects of PDE5 inhibitors, with the best effectiveness reported in middle-aged and mild-to-moderate ED patients. Respondents were confident about its overall safety, with a significant number expressing interest in RT's future use, despite pending guidelines support. CONCLUSIONS: This inaugural global survey reveals a growing use of RT in ED treatment, showcasing its diverse clinical applications and potential for future widespread adoption. However, the lack of comprehensive evidence and clear guidelines requires further research to standardize RT practices in ED treatment.

11.
Clin Exp Med ; 24(1): 119, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833206

RESUMO

Patients with hematologic malignancies (HMs) are at a significantly higher risk of contracting COVID-19 and experiencing severe outcomes compared to individuals without HMs. This heightened risk is influenced by various factors, including the underlying malignancy, immunosuppressive treatments, and patient-related factors. Notably, immunosuppressive regimens commonly used for HM treatment can lead to the depletion of B cells and T cells, which is associated with increased COVID-19-related complications and mortality in these patients. As the pandemic transitions into an endemic state, it remains crucial to acknowledge and address the ongoing risk for individuals with HMs. In this review, we aim to summarize the current evidence to enhance our understanding of the impact of HMs on COVID-19 risks and outcomes, identify particularly vulnerable individuals, and emphasize the need for specialized clinical attention and management. Furthermore, the impaired immune response to COVID-19 vaccination observed in these patients underscores the importance of implementing additional mitigation strategies. This may include targeted prophylaxis and treatment with antivirals and monoclonal antibodies as indicated. To provide practical guidance and considerations, we present two illustrative cases to highlight the real-life challenges faced by physicians caring for patients with HMs, emphasizing the need for individualized management based on disease severity, type, and the unique circumstances of each patient.


Assuntos
COVID-19 , Neoplasias Hematológicas , Humanos , COVID-19/complicações , COVID-19/imunologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , SARS-CoV-2/imunologia , Masculino , Antivirais/uso terapêutico , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Pessoa de Meia-Idade , Feminino
12.
Proteomics ; 24(14): e2300382, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38837544

RESUMO

Short-length antimicrobial peptides (AMPs) have been demonstrated to have intensified antimicrobial activities against a wide spectrum of microbes. Therefore, exploration of novel and promising short AMPs is highly essential in developing various types of antimicrobial drugs or treatments. In addition to experimental approaches, computational methods have been developed to improve screening efficiency. Although existing computational methods have achieved satisfactory performance, there is still much room for model improvement. In this study, we proposed iAMP-DL, an efficient hybrid deep learning architecture, for predicting short AMPs. The model was constructed using two well-known deep learning architectures: the long short-term memory architecture and convolutional neural networks. To fairly assess the performance of the model, we compared our model with existing state-of-the-art methods using the same independent test set. Our comparative analysis shows that iAMP-DL outperformed other methods. Furthermore, to assess the robustness and stability of our model, the experiments were repeated 10 times to observe the variation in prediction efficiency. The results demonstrate that iAMP-DL is an effective, robust, and stable framework for detecting promising short AMPs. Another comparative study of different negative data sampling methods also confirms the effectiveness of our method and demonstrates that it can also be used to develop a robust model for predicting AMPs in general. The proposed framework was also deployed as an online web server with a user-friendly interface to support the research community in identifying short AMPs.


Assuntos
Peptídeos Antimicrobianos , Aprendizado Profundo , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/farmacologia , Redes Neurais de Computação , Biologia Computacional/métodos , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia
13.
NPJ Breast Cancer ; 10(1): 42, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851818

RESUMO

The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment. Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient-derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.

14.
Cureus ; 16(5): e59977, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38854269

RESUMO

Although organ transplantation is associated with significant survival rates and cost benefits, postoperative complications still occur. Gastrointestinal complications, including those involving the stomach and intestines, account for 1-6% of posttransplant complications, with intestinal perforation specifically accounting for approximately 9%, depending on the center. In Vietnam, there are no comprehensive reports on these complications. Therefore, we report three clinical cases of gastrointestinal perforation following transplantation. Three cases of intestinal perforation are described in this case series. In 2023, a 16-year-old female patient who underwent heart transplantation for congenital heart disease was diagnosed with intestinal perforation on the 12th day. The patient required continued blood filtration support after surgery. In 2018, six days after liver transplantation, a 56-year-old male patient was diagnosed with intestinal perforation, which was subsequently repaired, and the ends of his intestines were removed. The patient was discharged in stable condition after 30 days. In 2017, five days after kidney transplantation, a 46-year-old female patient was diagnosed with intestinal perforation, which was repaired, and the perforation site was left open. The patient was discharged in stable condition after 40 days. Intestinal perforation is a relatively rare, but not uncommon, complication. Early diagnosis is challenging due to nonspecific clinical symptoms and signs. Considering the possibility of intestinal perforation and obtaining early abdominal computed tomography imaging can help prevent delayed diagnosis.

15.
Eur J Paediatr Neurol ; 51: 110-117, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38917695

RESUMO

BACKGROUND: NKX2-1-related disorder (NKX2-1-RD) is a rare disease characterized by a triad of primary hypothyroidism, neonatal respiratory distress, and neurological features, including chorea. OBJECTIVE: This study aimed to identify discrepancies in the management of NKX2-1-RD among European Union (EU) specialists. METHODS: The ERN-RND Chorea & Huntington disease group designed a survey to conduct a cross-sectional multicenter study on the management of NKX2-1-RD. Descriptive analysis was performed, and total responses are presented for each item. RESULTS: The study involved 23 experts from 13 EU countries with experience in evaluating hyperkinetic patients with NKX2-1-RD: 11 were adult specialists, and 12 were pediatric specialists. NKX2-1-RD diagnosis was made at different ages, with the most common initial symptoms being hypotonia and/or motor developmental delay (reported by 11 experts) and chorea (reported by 8 experts). Chorea involved various body parts and showed improvement as reported by 9 experts, stabilization by 12 experts, and worsening by 2 experts with age. The pharmacological treatment of chorea varied widely among the experts. Misdiagnosis was reported by 14 experts. NKX2-1 pathogenic variants or deletions were confirmed in >75 % of patients (reported by 12 experts). Pulmonary and endocrinology evaluations were requested by 7 and 12 experts, respectively. The management of psychiatric comorbidities also varied among the different experts. CONCLUSIONS: This study highlights the need for a clinical practice guideline for the management of NKX2-1-RD to ensure that patients across the EU receive consistent and appropriate care. Such a guideline would benefit both doctors and healthcare practitioners.

16.
Cancer Res ; 84(11): 1834-1855, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38831751

RESUMO

Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation of metabolites that reprogram the tumor microenvironment (TME) and drive cancer could facilitate development of precision nutrition approaches. Using the Hi-MYC prostate cancer mouse model, we demonstrated that an obesogenic high-fat diet (HFD) rich in saturated fats accelerates the development of c-MYC-driven invasive prostate cancer through metabolic rewiring. Although c-MYC modulated key metabolic pathways, interaction with an obesogenic HFD was necessary to induce glycolysis and lactate accumulation in tumors. These metabolic changes were associated with augmented infiltration of CD206+ and PD-L1+ tumor-associated macrophages (TAM) and FOXP3+ regulatory T cells, as well as with the activation of transcriptional programs linked to disease progression and therapy resistance. Lactate itself also stimulated neoangiogenesis and prostate cancer cell migration, which were significantly reduced following treatment with the lactate dehydrogenase inhibitor FX11. In patients with prostate cancer, high saturated fat intake and increased body mass index were associated with tumor glycolytic features that promote the infiltration of M2-like TAMs. Finally, upregulation of lactate dehydrogenase, indicative of a lactagenic phenotype, was associated with a shorter time to biochemical recurrence in independent clinical cohorts. This work identifies cooperation between genetic drivers and systemic metabolism to hijack the TME and promote prostate cancer progression through oncometabolite accumulation. This sets the stage for the assessment of lactate as a prognostic biomarker and supports strategies of dietary intervention and direct lactagenesis blockade in treating advanced prostate cancer. SIGNIFICANCE: Lactate accumulation driven by high-fat diet and MYC reprograms the tumor microenvironment and promotes prostate cancer progression, supporting the potential of lactate as a biomarker and therapeutic target in prostate cancer. See related commentary by Frigo, p. 1742.


Assuntos
Dieta Hiperlipídica , Ácido Láctico , Obesidade , Neoplasias da Próstata , Proteínas Proto-Oncogênicas c-myc , Microambiente Tumoral , Masculino , Animais , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos , Humanos , Ácido Láctico/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Obesidade/metabolismo , Obesidade/patologia , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Macrófagos Associados a Tumor/metabolismo
17.
Nat Prod Res ; : 1-8, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38824679

RESUMO

This study attempts to reveal antioxidants in the plant parts of Myxopyrum smilacifolium (Wall.) Blume using antioxidant assays and LC-MS/MS analysis. Methanol is the most effective solvent for collecting antioxidants. The roots-derived methanol extract demonstrates the greatest antioxidant activity, corresponding to the extremely low IC50 values of 16.39 µg/mL and 19.80 µg/mL for DPPH and ABTS radicals, respectively. The high phenolic and flavonoid contents are the primary reason for outstanding total antioxidant capacity (TAC; i.e. 247.73 ± 1.62 mg GA/g or 163.93 ± 0.83 mg AS/g) of the root extract. LC-MS/MS quantification of five phenolic compounds reveals exceptionally high amounts of quercetin and luteolin in the root extract, ranging from 238.86 ± 5.74 to 310.99 ± 1.44 µg/g and from 201.49 ± 7.84 to 234.10 ± 2.54 µg/g, respectively, in the root-derived methanol extract. The achievement highlights M. smilacifolium as a promising source of natural antioxidants for large-scale medical applications.

18.
Int J Gen Med ; 17: 2489-2495, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38826506

RESUMO

Purpose: Chyluria is a rare condition primarily prevalent in developing countries in tropical regions. In chyluria, there exists the communication between lymphatic vessels and the urinary tract, but the specific mechanism of this communication remains undocumented. The objective of this study was to assess the morphology of the main lymphatic vessels including the uro-lymphatic fistula, the thoracic duct using Magnetic Resonance Lymphangiography (MRL) and Intranodal Lymphangiography (IL). Materials and Methods: A retrospective study spanning five years, from January 2020 to January 2024, included 43 patients diagnosed with chyluria through cystoscopy and quantitative urine testing for triglycerides. These patients underwent MRL and then IL for uro-lymphatic fistula embolization. Results: The study involved 43 patients with an average age of 66.1 ± 19.5 years, with a male-to-female ratio of 1:2. Uro-lymphatic fistula occurred predominantly in the left kidney (72.1%), followed by the right kidney (20.9%), and both sides (7%). MRL imaging showed the thoracic duct in 100% of cases but visualized only 84.5% of the uro-lymphatic fistulas. In contrast, IL imaging showed the thoracic duct in 51.5% of patients but visualized uro-lymphatic fistulas in 100% of cases. In the procedure of IL, the average visualization time of the thoracic duct was 45 minutes, with a range of 35 to 69 minutes. Conclusion: MRL and IL complement each other in diagnosing the main lymphatic vessels in chyluria patients. The observed circulatory stasis in the thoracic duct supports the hypothesis that it contributes to increased pressure in the thoracic duct and the formation uro-lymphatic fistula as collateral circulations.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38853578

RESUMO

Objectives: This study was conducted to investigate the prevalence of mental health (MH) symptoms and associated factors among medical students who were engaged in combating the coronavirus disease 2019 (COVID-19) epidemic in 4 provinces/cities of Vietnam. Methods: A cross-sectional study with 580 participants was conducted at a medical university in Northern Vietnam. MH was assessed using the 21-item Depression, Anxiety, and Stress Scale, which was previously standardized in Vietnam. Data were collected through a structured self-administered questionnaire. Multivariate logistic regression was employed to examine the association between MH symptoms and relevant factors. Results: Of 2,703 total medical students, 21.5% responded to the questionnaire. Among the 580 respondents, the prevalence rates of depression, anxiety, and stress were 43.3%, 44%, and 24.7%, respectively. Factors significantly associated with self-reported depression included female sex and infection with COVID-19. Similarly, female sex and COVID-19 infection were significantly associated with self-reported anxiety. Factors linked to self-reported stress included female sex, a personal or family history of MH symptoms, working more than 8 hours per day, and COVID-19 infection. Conclusion: COVID-19 has adversely impacted the MH of medical students. Our findings are valuable in their potential to motivate universities, MH professionals, and authorities to offer mental healthcare services to this group. Furthermore, there is a pressing need for training courses designed to equip future healthcare workers with the skills to manage crises effectively.

20.
Eval Rev ; : 193841X241260466, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850272

RESUMO

Cooperation between employees in a company is an important input to firm performance. This study examines how a manager's cooperative behavior and the visibility of this behavior affect the cooperation amongst employees, and subsequently firm performance. To do so, we conducted a field experiment with managers and their employees from 320 Vietnamese small and micro firms to determine the impact of a manager's leading by example (LBE) on employees' behavior, corporate culture, and firm performance. Both managers and employees participated in a Public Good experiment which aimed to elicit an individual cooperative behavior. Noteworthy is that the decision made by a manager in the experiment was given as an example to employees before they made decision in that same experiment. We considered that the example of cooperation by managers in the Public Good experiment communicated a powerful signal to the employees regarding the importance of fostering cooperation in the workplace. Such a signal by the manager, who is at the top in the organizational hierarchy, would impact their employees' behavior in the workplace and firm's outcomes beyond the experiment. Interestingly, we found that concealing a manager's identity from their employees enhances the impacts of LBE.

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