Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 78
Filtrar
1.
Ultrasound Med Biol ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39138026

RESUMO

OBJECTIVES: To assess the capabilities of large language models (LLMs), including Open AI (GPT-4.0) and Microsoft Bing (GPT-4), in generating structured reports, the Breast Imaging Reporting and Data System (BI-RADS) categories, and management recommendations from free-text breast ultrasound reports. MATERIALS AND METHODS: In this retrospective study, 100 free-text breast ultrasound reports from patients who underwent surgery between January and May 2023 were gathered. The capabilities of Open AI (GPT-4.0) and Microsoft Bing (GPT-4) to convert these unstructured reports into structured ultrasound reports were studied. The quality of structured reports, BI-RADS categories, and management recommendations generated by GPT-4.0 and Bing were evaluated by senior radiologists based on the guidelines. RESULTS: Open AI (GPT-4.0) was better than Microsoft Bing (GPT-4) in terms of performance in generating structured reports (88% vs. 55%; p < 0.001), giving correct BI-RADS categories (54% vs. 47%; p = 0.013) and providing reasonable management recommendations (81% vs. 63%; p < 0.001). As the ability to predict benign and malignant characteristics, GPT-4.0 performed significantly better than Bing (AUC, 0.9317 vs. 0.8177; p < 0.001), while both performed significantly inferior to senior radiologists (AUC, 0.9763; both p < 0.001). CONCLUSION: This study highlights the potential of LLMs, specifically Open AI (GPT-4.0), in converting unstructured breast ultrasound reports into structured ones, offering accurate diagnoses and providing reasonable recommendations.

2.
Shanghai Kou Qiang Yi Xue ; 33(2): 148-155, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-39005090

RESUMO

PURPOSE: The purpose of this study was to explore the expression, prognostic value and immune correlation of Cofilin 1 protein(CFL-1) in head and neck squamous cell carcinoma(HNSCC). METHODS: The expression and prognostic value of CFL-1 in head and neck squamous cell carcinoma(HNSCC) was explored in the cancer genome map database (TCGA) and gene expression total databases (GEO), and the potential immune pathway of CFL-1 in HNSCC was revealed by GESA and cibersoft analysis. The data were statistically analyzed using SPSS 26.0 software package. RESULTS: CFL-1 was significantly up-regulated in HNSCC tissue. The expression level of CFL-1 was significantly correlated with the overall survival status of HNSCC. High expression of CFL-1 was significantly associated with a lower overall survival rate. In addition, multivariate Cox survival analysis showed that CFL-1 expression was independent predictors of poor prognosis of HNSCC. GESA and cibersoft analysis showed that the imbalance of CFL-1 expression affected multiple signal pathways and infiltration of immune cells. CONCLUSIONS: CFL-1 is highly expressed in HNSCC and is significantly associated with poor prognosis of NHSCC. It is a potential prognostic marker of HNSCC.


Assuntos
Cofilina 1 , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Cofilina 1/genética , Cofilina 1/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/metabolismo , Taxa de Sobrevida , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Modelos de Riscos Proporcionais
3.
Mol Pharm ; 21(8): 3743-3763, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38953708

RESUMO

The coronavirus (COVID-19) pandemic has underscored the critical role of mRNA-based vaccines as powerful, adaptable, readily manufacturable, and safe methodologies for prophylaxis. mRNA-based treatments are emerging as a hopeful avenue for a plethora of conditions, encompassing infectious diseases, cancer, autoimmune diseases, genetic diseases, and rare disorders. Nonetheless, the in vivo delivery of mRNA faces challenges due to its instability, suboptimal delivery, and potential for triggering undesired immune reactions. In this context, the development of effective drug delivery systems, particularly nanoparticles (NPs), is paramount. Tailored with biophysical and chemical properties and susceptible to surface customization, these NPs have demonstrated enhanced mRNA delivery in vivo and led to the approval of several NPs-based formulations for clinical use. Despite these advancements, the necessity for developing a refined, targeted NP delivery system remains imperative. This review comprehensively surveys the biological, translational, and clinical progress in NPs-mediated mRNA therapeutics for both the prevention and treatment of diverse diseases. By addressing critical factors for enhancing existing methodologies, it aims to inform the future development of precise and efficacious mRNA-based therapeutic interventions.


Assuntos
COVID-19 , Sistemas de Liberação de Fármacos por Nanopartículas , RNA Mensageiro , Humanos , RNA Mensageiro/genética , RNA Mensageiro/administração & dosagem , Sistemas de Liberação de Fármacos por Nanopartículas/química , COVID-19/prevenção & controle , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Animais , SARS-CoV-2/efeitos dos fármacos , Vacinas de mRNA
4.
Int J Oral Sci ; 16(1): 52, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39085217

RESUMO

Compared with teenage patients, adult patients generally show a slower rate of tooth movement and more pronounced alveolar bone loss during orthodontic treatment, indicating the maladaptation of alveolar bone homeostasis under orthodontic force. However, this phenomenon is not well-elucidated to date, leading to increased treatment difficulties and unsatisfactory treatment outcomes in adult orthodontics. Aiming to provide a comprehensive knowledge and further inspire insightful understanding towards this issue, this review summarizes the current evidence and underlying mechanisms. The age-related abatements in mechanosensing and mechanotransduction in adult cells and periodontal tissue may contribute to retarded and unbalanced bone metabolism, thus hindering alveolar bone reconstruction during orthodontic treatment. To this end, periodontal surgery, physical and chemical cues are being developed to reactivate or rejuvenate the aging periodontium and restore the dynamic equilibrium of orthodontic-mediated alveolar bone metabolism. We anticipate that this review will present a general overview of the role that aging plays in orthodontic alveolar bone metabolism and shed new light on the prospective ways out of the impasse.


Assuntos
Adaptação Fisiológica , Envelhecimento , Perda do Osso Alveolar , Processo Alveolar , Humanos , Adulto , Envelhecimento/fisiologia , Adaptação Fisiológica/fisiologia , Técnicas de Movimentação Dentária , Mecanotransdução Celular/fisiologia , Remodelação Óssea/fisiologia
5.
Cancer Innov ; 3(4): e127, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38948249

RESUMO

Background: Clinical studies have shown that atherosclerotic cardiovascular disease and cancer often co-exist in the same individual. The present study aimed to investigate the role of high-fat-diet (HFD)-induced obesity in the coexistence of the two diseases and the underlying mechanism in apolipoprotein E-knockout (ApoE-/-) mice. Methods: Male ApoE-/- mice were fed with a HFD or a normal diet (ND) for 15 weeks. On the first day of Week 13, the mice were inoculated subcutaneously in the right axilla with Lewis lung cancer cells. At Weeks 12 and 15, serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and vascular endothelial growth factor levels were measured by enzyme-linked immunosorbent assay, and blood monocytes and macrophages were measured by fluorescence-activated cell sorting. At Week 15, the volume and weight of the local subcutaneous lung cancer and metastatic lung cancer and the amount of aortic atherosclerosis were measured. Results: At Week 15, compared with mice in the ND group, those in the HFD group had a larger volume of local subcutaneous cancer (p = 0.0004), heavier tumors (p = 0.0235), more metastatic cancer in the lungs (p < 0.0001), a larger area of lung involved in metastatic cancer (p = 0.0031), and larger areas of atherosclerosis in the aorta (p < 0.0001). At Week 12, serum LOX-1, serum vascular endothelial growth factor, and proportions of blood monocytes and macrophages were significantly higher in the HFD group than those in the ND group (p = 0.0002, p = 0.0029, p = 0.0480, and p = 0.0106, respectively); this trend persisted until Week 15 (p = 0.0014, p = 0.0012, p = 0.0001, and p = 0.0204). Conclusions: In this study, HFD-induced obesity could simultaneously promote progression of lung cancer and atherosclerosis in the same mouse. HFD-induced upregulation of LOX-1 may play an important role in the simultaneous progression of these two conditions via the inflammatory response and VEGF.

6.
Front Pharmacol ; 15: 1379166, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38910895

RESUMO

Maintaining the structural integrity of genomic chromosomal DNA is an essential role of cellular life and requires two important biological mechanisms: the DNA damage response (DDR) mechanism and telomere protection mechanism at chromosome ends. Because abnormalities in telomeres and cellular DDR regulation are strongly associated with human aging and cancer, there is a reciprocal regulation of telomeres and cellular DDR. Moreover, several drug treatments for DDR are currently available. This paper reviews the progress in research on the interaction between telomeres and cellular DNA damage repair pathways. The research on the crosstalk between telomere damage and DDR is important for improving the efficacy of tumor treatment. However, further studies are required to confirm this hypothesis.

7.
Cancer Lett ; 595: 217025, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-38844063

RESUMO

Despite the confirmed role of LKB1 in suppressing lung cancer progression, its precise effect on cellular senescence is unknown. The aim of this research was to clarify the role and mechanism of LKB1 in restraining telomerase activity in lung adenocarcinoma. The results showed that LKB1 induced cellular senescence and apoptosis either in vitro or in vivo. Overexpression of LKB1 in LKB1-deficient A549 cells led to the inhibition of telomerase activity and the induction of telomere dysfunction by regulating telomerase reverse transcriptase (TERT) expression in terms of transcription. As a transcription factor, Sp1 mediated TERT inhibition after LKB1 overexpression. LKB1 induced lactate production and inhibited histone H4 (Lys8) and H4 (Lys16) lactylation, which further altered Sp1-related transcriptional activity. The telomerase inhibitor BIBR1532 was beneficial for achieving the optimum curative effect of traditional chemotherapeutic drugs accompanied by the glycolysis inhibitor 2DG. These data reveal a new mechanism by which LKB1 regulates telomerase activity through lactylation-dependent transcriptional inhibition, and therefore, provide new insights into the effects of LKB1-mediated senescence in lung adenocarcinoma. Our research has opened up new possibilities for the creation of new cancer treatments.


Assuntos
Quinases Proteína-Quinases Ativadas por AMP , Adenocarcinoma de Pulmão , Senescência Celular , Histonas , Neoplasias Pulmonares , Proteínas Serina-Treonina Quinases , Fator de Transcrição Sp1 , Telomerase , Animais , Humanos , Camundongos , Células A549 , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/tratamento farmacológico , Quinases Proteína-Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Senescência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Camundongos Nus , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Fator de Transcrição Sp1/metabolismo , Fator de Transcrição Sp1/genética , Telomerase/metabolismo , Telomerase/genética , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Exp Dermatol ; 33(6): e15097, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840370

RESUMO

Surgical management of basal cell carcinoma (BCC) typically involves surgical excision with post-operative margin assessment using the bread-loafing technique; or gold-standard Mohs micrographic surgery (MMS), where margins are iteratively examined for residual cancer after tumour removal, with additional excisions performed upon detecting residual tumour at margins. There is limited sampling of resection margins with bread loafing, with detection of positive margins 44% of the time using 2 mm intervals. To resolve this, we have developed three-dimensional (3D) Tissue Imaging for: (1) complete examination of cancer margins and (2) detection of tumour proximity to nerves and blood vessels. 3D Tissue optical clearing with a light sheet imaging protocol was developed for margin assessment in two datasets assessed by two independent evaluators: (1) 48 samples from 29 patients with varied BCC subtypes, sizes and pigmentation levels; (2) 32 samples with matching Mohs' surgeon reading of tumour margins using two-dimensional haematoxylin & eosin-stained sections. The 3D Tissue Imaging protocol permits a complete examination of deeper and peripheral margins. Two independent evaluators achieved negative predictive values of 92.3% and 88.24% with 3D Tissue Imaging. Images obtained from 3D Tissue Imaging recapitulates histological features of BCC, such as nuclear crowding, palisading and retraction clefting and provides a 3D context for recognising normal skin adnexal structures. Concurrent immunofluorescence labelling of nerves and blood vessels allows visualisation of structures closer to tumour-positive regions, which may have a higher risk for neural and vascular infiltration. Together, this method provides more information in a 3D spatial context, enabling better cancer management by clinicians.


Assuntos
Carcinoma Basocelular , Imageamento Tridimensional , Margens de Excisão , Cirurgia de Mohs , Neoplasias Cutâneas , Humanos , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/cirurgia , Carcinoma Basocelular/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia
10.
Int J Biol Macromol ; 268(Pt 1): 131679, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38641274

RESUMO

Over the past few decades, significant strides have been made in understanding the pivotal roles that chemokine networks play in tumor biology. These networks, comprising chemokines and their receptors, wield substantial influence over cancer immune regulation and therapeutic outcomes. As a result, targeting these chemokine systems has emerged as a promising avenue for cancer immunotherapy. However, therapies targeting chemokines face significant challenges in solid tumor treatment, due to the complex and fragile of the chemokine networks. A nuanced comprehension of the complicacy and functions of chemokine networks, and their impact on the tumor microenvironment, is essential for optimizing their therapeutic utility in oncology. This review elucidates the ways in which chemokine networks interact with cancer immunity and tumorigenesis. We particularly elaborate on recent innovations in manipulating these networks for cancer treatment. The review also highlights future challenges and explores potential biomaterial strategies for clinical applications.


Assuntos
Quimiocinas , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Quimiocinas/metabolismo , Animais , Imunoterapia/métodos , Portadores de Fármacos/química , Nanopartículas/química , Nanopartículas/uso terapêutico , Receptores de Quimiocinas/metabolismo
11.
Prostate ; 84(9): 807-813, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38558009

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition, yet it is challenging for the average BPH patient to find credible and accurate information about BPH. Our goal is to evaluate and compare the accuracy and reproducibility of large language models (LLMs), including ChatGPT-3.5, ChatGPT-4, and the New Bing Chat in responding to a BPH frequently asked questions (FAQs) questionnaire. METHODS: A total of 45 questions related to BPH were categorized into basic and professional knowledge. Three LLM-ChatGPT-3.5, ChatGPT-4, and New Bing Chat-were utilized to generate responses to these questions. Responses were graded as comprehensive, correct but inadequate, mixed with incorrect/outdated data, or completely incorrect. Reproducibility was assessed by generating two responses for each question. All responses were reviewed and judged by experienced urologists. RESULTS: All three LLMs exhibited high accuracy in generating responses to questions, with accuracy rates ranging from 86.7% to 100%. However, there was no statistically significant difference in response accuracy among the three (p > 0.017 for all comparisons). Additionally, the accuracy of the LLMs' responses to the basic knowledge questions was roughly equivalent to that of the specialized knowledge questions, showing a difference of less than 3.5% (GPT-3.5: 90% vs. 86.7%; GPT-4: 96.7% vs. 95.6%; New Bing: 96.7% vs. 93.3%). Furthermore, all three LLMs demonstrated high reproducibility, with rates ranging from 93.3% to 97.8%. CONCLUSIONS: ChatGPT-3.5, ChatGPT-4, and New Bing Chat offer accurate and reproducible responses to BPH-related questions, establishing them as valuable resources for enhancing health literacy and supporting BPH patients in conjunction with healthcare professionals.


Assuntos
Hiperplasia Prostática , Humanos , Hiperplasia Prostática/diagnóstico , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários , Idioma , Educação de Pacientes como Assunto/métodos
12.
Nanotechnology ; 35(27)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38574479

RESUMO

This article investigates the radiation effects on as-deposited and annealed AlN films on 4H-SiC substrates under gamma-rays. The AlN films are prepared using plasma-enhanced-atomic-layer-deposition on an n-type 4H-SiC substrate. The AlN/4H-SiC MIS structure is subjected to gamma-ray irradiation with total doses of 0, 300, and 600 krad(Si). Physical, chemical, and electrical methods were employed to study the variations in surface morphology, charge transport, and interfacial trapping characteristics induced by irradiation. After 300 krad(Si) irradiation, the as-deposited and annealed samples exhibit their highest root mean square values of 0.917 nm and 1.190 nm, respectively, which is attributed to N vacancy defects induced by irradiation. Under irradiation, the flatband voltage (Vfb) of the as-deposited sample shifts from 2.24 to 0.78 V, while the annealed sample shifts from 1.18 to 2.16 V. X-ray photoelectron spectrum analysis reveals the decomposition of O-related defects in the as-deposited AlN and the formation of Al(NOx)ycompounds in the annealed sample. Furthermore, the space-charge-limits-conduction (SCLC) in the as-deposited sample is enhanced after radiation, while the barrier height of the annealed sample decreases from 1.12 to 0.84 eV, accompanied by the occurrence of the SCLC. The physical mechanism of the degradation of electrical performance in irradiated devices is the introduction of defects like N vacancies and O-related defects like Al(NOx)y. These findings provide valuable insights for SiC power devices in space applications.

13.
Langmuir ; 40(8): 4447-4459, 2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38349871

RESUMO

High-sensitivity detection of biomarkers is of great significance to improve the accuracy of disease diagnosis and the rate of occult disease diagnosis. Using a substrate modification and two-color quantum dot (QD) nanobeads (QBs), we have developed a dual fluorescence signal-enhancement immunosensor for sensitive, simultaneous detection of interleukin 6 (IL-6) and procalcitonin (PCT) at low volumes (∼20 µL). First, the QBs compatible with QDs with different surface ligands were prepared by optimizing surfactants based on the microemulsion method. Through the use of a fluorescence-linked immunosorbent assay (FLISA), the feasibility of a dual signal-enhancement immunosensor was verified, and a 5-fold enhancement of fluorescence intensity was achieved after the directional coating of the antibodies on sulfhydryl functionalization (-SH) substrates and the preparation of QBs by using a polymer and silica double-protection method. Next, a simple polydimethylsiloxane (HS-PDMS) immunosensor with a low volume consumption was prepared. Under optimal conditions, we achieved the simultaneous detection of IL-6 and PCT with a linear range of 0.05-50 ng/mL, and the limit of detection (LOD) was 24 and 32 pg/mL, respectively. The result is comparable to two-color QBs-FLISA with a sulfhydryl microplate, even though only 20% of its volume was used. Thus, the dual fluorescence signal-enhancement HS-PDMS immunosensor offers the capability of early microvolume diagnosis of diseases, while the detection of inflammatory factors is clinically important for assisting disease diagnosis and determining disease progression.


Assuntos
Técnicas Biossensoriais , Pontos Quânticos , Pró-Calcitonina , Interleucina-6 , Imunoensaio/métodos , Técnicas Biossensoriais/métodos , Limite de Detecção
14.
Science ; 383(6679): eadf6493, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38207030

RESUMO

Neutrophils are increasingly recognized as key players in the tumor immune response and are associated with poor clinical outcomes. Despite recent advances characterizing the diversity of neutrophil states in cancer, common trajectories and mechanisms governing the ontogeny and relationship between these neutrophil states remain undefined. Here, we demonstrate that immature and mature neutrophils that enter tumors undergo irreversible epigenetic, transcriptional, and proteomic modifications to converge into a distinct, terminally differentiated dcTRAIL-R1+ state. Reprogrammed dcTRAIL-R1+ neutrophils predominantly localize to a glycolytic and hypoxic niche at the tumor core and exert pro-angiogenic function that favors tumor growth. We found similar trajectories in neutrophils across multiple tumor types and in humans, suggesting that targeting this program may provide a means of enhancing certain cancer immunotherapies.


Assuntos
Reprogramação Celular , Neoplasias , Neovascularização Patológica , Neutrófilos , Humanos , Neoplasias/irrigação sanguínea , Neoplasias/imunologia , Neutrófilos/imunologia , Proteômica , Reprogramação Celular/genética , Reprogramação Celular/imunologia , Neovascularização Patológica/genética , Neovascularização Patológica/imunologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/imunologia , Epigênese Genética , Hipóxia , Transcrição Gênica
15.
Cell Death Dis ; 15(1): 90, 2024 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-38278800

RESUMO

Abnormal activation of telomerase occurs in most cancer types, which facilitates escaping from cell senescence. As the key component of telomerase, telomerase reverse transcriptase (TERT) is regulated by various regulation pathways. TERT gene changing in its promoter and phosphorylation respectively leads to TERT ectopic expression at the transcription and protein levels. The co-interacting factors play an important role in the regulation of TERT in different cancer types. In this review, we focus on the regulators of TERT and these downstream functions in cancer regulation. Determining the specific regulatory mechanism will help to facilitate the development of a cancer treatment strategy that targets telomerase and cancer cell senescence. As the most important catalytic subunit component of telomerase, TERT is rapidly regulated by transcriptional factors and PTM-related activation. These changes directly influence TERT-related telomere maintenance by regulating telomerase activity in telomerase-positive cancer cells, telomerase assembly with telomere-binding proteins, and recruiting telomerase to the telomere. Besides, there are also non-canonical functions that are influenced by TERT, including the basic biological functions of cancer cells, such as proliferation, apoptosis, cell cycle regulation, initiating cell formation, EMT, and cell invasion. Other downstream effects are the results of the influence of transcriptional factors by TERT. Currently, some small molecular inhibitors of TERT and TERT vaccine are under research as a clinical therapeutic target. Purposeful work is in progress.


Assuntos
Neoplasias , Telomerase , Telomerase/genética , Telomerase/metabolismo , Senescência Celular , Fosforilação , Telômero/genética , Telômero/metabolismo , Neoplasias/genética , Neoplasias/metabolismo
16.
Ecotoxicol Environ Saf ; 267: 115661, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37948941

RESUMO

With the intensifying climate warming, blue-green algae blooms have become more frequent and severe, releasing environmental hazards such as microcystin that pose potential threats to human and animal health. Autophagy has been shown to play a crucial role in regulating immune responses induced by environmental hazards, enabling cells to adapt to stress and protect against damage. Although microcystin-LR (MC-LR) has been identified to affect autophagy in mammalian, its impact on aquatic animals has been poorly studied. To investigate the toxicological effects of MC-LR in aquatic ecosystems, we constructed a microRNA profile of acute MC-LR stress in the hepatopancreas of the Chinese mitten crab. Interestingly, we found the MC-LR exposure activated autophagy in the hepatopancreas based on the following evidence. Specifically, mRNA expression level of ATG7, Beclin1 and Gabarap was significantly up-regulated, autophagy regulatory pathways were significantly enriched, and numerous autolysosomes and autophagosomes were observed. Additionally, we found that miR-282-5p and its target gene PIK3R1 played important regulatory roles in autophagy by in vivo and in vitro experiments. Overexpression of miR-282-5p mimicked MC-LR-induced autophagy by inhibiting PIK3R1 expression, while miR-282-5p silencing inhibited autophagy by promoting PIK3R1 expression. Altogether, our findings suggest that MC-LR increases miR-282-5p, which then targets inhibition of PIK3R1 to stimulate autophagy. This study focused on the stress response regulatory mechanisms of juvenile crabs to toxic pollutants in water, offering a potential target for alleviating the toxicity of MC-LR. These findings lay a foundation for reducing the toxicity of MC-LR and environmental hazards in organisms.


Assuntos
MicroRNAs , Microcistinas , Animais , Humanos , Microcistinas/toxicidade , Hepatopâncreas/metabolismo , Ecossistema , Fatores de Transcrição , MicroRNAs/genética , MicroRNAs/metabolismo , Autofagia , Mamíferos/metabolismo , Classe Ia de Fosfatidilinositol 3-Quinase
17.
Front Med (Lausanne) ; 10: 1265148, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37809345

RESUMO

Background: Chronic pruritus of unknown origin (CPUO) is poorly understood and lacks effective treatment options. Objectives: We aimed to elucidate abnormalities in the sweat apparatus of patients with CPUO, and to assess efficacy and safety of treatment with systemic retinoids. Methods: An initial case-control study included 20 affected patients and five healthy controls, for whom heat and sweating were induced, either through a standardized exercise protocol or ingestion of hot water. In vivo high-definition optical coherence tomography, whole-body starch-iodine testing, and skin biopsy for immunofluorescence staining were done to evaluate for sweat duct obstruction. A subsequent retrospective cohort analysis included 56 patients with CPUO, seen at an Itch subspecialty clinic of a single tertiary referral centre, who failed conventional treatments and were treated with isotretinoin and/or acitretin from May 2014 to November 2020. Treatment response to retinoids was defined as a sustained reduction in itch score of ≥2/10. Safety was assessed by proportion stopping treatment due to side effects. Results: In vivo imaging in 19 (95%) patients revealed features of partial keratinaceous sweat duct obstruction with statistically significant luminal dilatation compared to controls. Immunofluorescence studies of three patients' paired lesional/non-lesional biopsies revealed dermcidin accumulation within sweat glands coupled with dermcidin leakage in itchy skin. Fifty-six patients (mean [SD] age 55.2 [17.5] years, 69.6% male) were treated with systemic retinoids. Mean (SD) duration of itch was 116.3 (140.4) months and mean (SD) itch score was 8.2 (1.8). Forty-one (73.2%) initially received isotretinoin, and 15 (26.8%) acitretin. At three months, mean itch score reduced by 2.38 (95% CI -3.2 to -1.6, p < 0.0001). Thirty-eight (67.9%) had a sustained response. Eight (14.81%) achieved an itch score of 0 or 1, with four stopping treatment for a mean (SD) of 318.5 (291.2) days without relapse. Eight (14.3%) stopped or switched retinoid due to adverse effects, with similar incidences between both retinoids, the commonest being dryness. Conclusion: Based on novel findings from physiological imaging studies identifying partial keratinaceous sweat duct obstruction in CPUO, we instituted systemic retinoid treatment to address the underlying pathology. In patients who failed conventional therapies, the treatment appears effective and safe.

18.
Nucleic Acids Res ; 51(21): 11600-11612, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37889068

RESUMO

Cooperative DNA-binding by transcription factor (TF) proteins is critical for eukaryotic gene regulation. In the human genome, many regulatory regions contain TF-binding sites in close proximity to each other, which can facilitate cooperative interactions. However, binding site proximity does not necessarily imply cooperative binding, as TFs can also bind independently to each of their neighboring target sites. Currently, the rules that drive cooperative TF binding are not well understood. In addition, it is oftentimes difficult to infer direct TF-TF cooperativity from existing DNA-binding data. Here, we show that in vitro binding assays using DNA libraries of a few thousand genomic sequences with putative cooperative TF-binding events can be used to develop accurate models of cooperativity and to gain insights into cooperative binding mechanisms. Using factors ETS1 and RUNX1 as our case study, we show that the distance and orientation between ETS1 sites are critical determinants of cooperative ETS1-ETS1 binding, while cooperative ETS1-RUNX1 interactions show more flexibility in distance and orientation and can be accurately predicted based on the affinity and sequence/shape features of the binding sites. The approach described here, combining custom experimental design with machine-learning modeling, can be easily applied to study the cooperative DNA-binding patterns of any TFs.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Regulação da Expressão Gênica , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Sítios de Ligação/genética , Ligação Proteica , DNA/química
19.
Crit Rev Food Sci Nutr ; : 1-22, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37819268

RESUMO

Milk contains bioactive compounds that have multiple essential benefits. Milk-derived small extracellular vesicles (M-sEVs) have emerged as novel bioactive milk components with various beneficial biological functions and broad applications. The M-sEVs from different mammalian sources have similar composition and bioactive functions. The digestive stability and biocompatibility of the M-sEVs provide a good foundation for their physiological functions. Evidence suggests that M-sEVs promote intestinal, immune, bone, neural, liver, and heart health and show therapeutic effects against cancer, indicating their potential for use in functional foods. In addition, M-sEVs can be developed as natural delivery carriers owing to their superior structural characteristics. Further studies are needed to elucidate the relationship between the specific components and functions of M-sEVs, standardize their extraction processes, and refine relevant clinical trials to advance the future applications of M-sEVs. This review summarizes the structure and composition of M-sEVs isolated from different milk sources and discusses several common extraction methods. Since the introduction of M-sEVs for digestion and absorption, studies have been conducted on their biological functions. Furthermore, we outline the theoretical industrial production route, potential application scenarios of M-sEVs, and the future perspectives of M-sEV research.

20.
World J Gastrointest Surg ; 15(7): 1532-1541, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37555104

RESUMO

BACKGROUND: Hypereosinophilic syndrome (HES) is classified as primary, secondary or idiopathic. Idiopathic HES (IHES) has a variable clinical presentation and may involve multiple organs causing severe damage. Hepatic sinusoidal obstruction syndrome (HSOS) is characterized by damage to the endothelial cells of the hepatic sinusoids of the hepatic venules, with occlusion of the hepatic venules, and hepatocyte necrosis. We report a case of IHES with HSOS of uncertain etiology. CASE SUMMARY: A 70-year-old male patient was admitted to our hospital with pruritus and a rash on the extremities for > 5 mo. He had previously undergone antiallergic treatment and herbal therapy in the local hospital, but the symptoms recurred. Relevant examinations were completed after admission. Bone marrow aspiration biopsy showed a significantly higher percentage of eosinophils (23%) with approximately normal morphology. Ultrasound-guided hepatic aspiration biopsy indicated HSOS. Contrast-enhanced computed tomography (CT) of the upper abdomen showed hepatic venule congestion with hydrothorax and ascites. The patient was initially diagnosed with IHES and hepatic venule occlusion. Prednisone, low molecular weight heparin and ursodeoxycholic acid were given for treatment, followed by discontinuation of low molecular weight heparin due to ecchymosis. Routine blood tests, biochemical tests, and imaging such as enhanced CT of the upper abdomen and pelvis were reviewed regularly. CONCLUSION: Hypereosinophilia may play a facilitating role in the occurrence and development of HSOS.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA