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1.
World J Gastrointest Surg ; 16(7): 2135-2144, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39087125

RESUMO

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

2.
JAMIA Open ; 7(3): ooae068, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39100988

RESUMO

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

3.
Redox Biol ; 75: 103299, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39127016

RESUMO

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

4.
Sci Rep ; 14(1): 18699, 2024 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134573

RESUMO

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


Assuntos
Cicatriz , Estética , Lábio , Humanos , Lábio/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Procedimentos de Cirurgia Plástica/métodos , Idoso , Retalhos Cirúrgicos , Resultado do Tratamento
5.
Aging Cell ; : e14320, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39158018

RESUMO

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

6.
Heliyon ; 10(12): e33458, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39027435

RESUMO

Sepsis is a syndrome that causes dysfunction of multiple organs due to the host's uncontrolled response to infection and is a significant contributor to morbidity and mortality in intensive care units worldwide. Surviving patients are often left with acute brain injury and long-term cognitive impairment, known as sepsis-associated encephalopathy (SAE). In recent years, researchers have directed their focus towards the pathogenesis of SAE. However, due to the complexity of its development, there remains a lack of effective treatment measures that arise as a serious issue affecting the prognosis of sepsis patients. Further research on the possible causes of SAE aims to provide clinicians with potential therapeutic targets and help develop targeted prevention strategies. This paper aims to review recent research on the pathogenesis of SAE, in order to enhance our understanding of this syndrome.

7.
ACS Omega ; 9(29): 31620-31630, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39072059

RESUMO

Solid polymer electrolytes have attracted considerable attention, owing to their flexibility and safety. At present, poly(ethylene oxide) is the most widely studied polymer electrolyte matrix. It exhibits higher safety than the polyolefin diaphragm used in traditional lithium-ion batteries. However, it readily crystallizes at room temperature, resulting in low ionic conductivity, and the preparation process involves organic solvents. In this study, from the perspective of molecular design, solvent-free polyaspartate polyurea (PAEPU) and the cheap and easily available polypropylene (PP) nonwoven fabric were used as support materials for the PAEPU/PP composite solid polymer electrolyte (PAEPU/PP m -CPE). This CPE has good thermal stability, dimensional stability, flexibility, and mechanical properties. Among the different CPEs that were analyzed, PAEPU/PP10-CPE@20 had the highest ionic conductivity, which was reinforced with 10 g/m2 PP nonwoven fabric and the content of lithium salt was 20 wt %. Furthermore, PAEPU/PP10-CPE@20 exhibited the highest electrochemical stability with an electrochemical window value of 5.53 V. Moreover, the capacity retention rate of the Li//PAEPU/PP10-CPE@20//LiFePO4 half-cell was 96.82% after 150 cycles at 0.05 C and 60 °C, and the capacity recovery rate in the rate test reached 98.81%.

8.
World J Gastrointest Oncol ; 16(7): 3011-3031, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39072151

RESUMO

BACKGROUND: Adipocytes, especially adipocytes within tumor tissue known as cancer-associated adipocytes, have been increasingly recognized for their pivotal role in the tumor microenvironment of gastric cancer (GC). Their influence on tumor progression and patient prognosis has sparked significant interest in recent research. The main objectives of this study were to investigate adipocyte infiltration, assess its correlation with clinical pathological features, develop a prognostic prediction model based on independent prognostic factors, evaluate the impact of adipocytes on immune cell infiltration and tumor invasiveness in GC, and identify and validate genes associated with high adipocyte expression, exploring their potential diagnostic and prognostic value. AIM: To explore the relationship between increased adipocytes within tumor tissue and prognosis in GC patients as well as the associated mechanisms and potential biomarkers, using public databases and clinical data. METHODS: Using mRNA microarray datasets from the Gene Expression Omnibus database and clinical samples from Jiangsu Provincial Hospital, survival and regression analyses were conducted to determine the relevant prognostic factors in GC. Feature gene selection was performed using least absolute shrinkage and selection operator and support vector machine recursive feature elimination algorithms, followed by differential gene expression analysis, gene ontology, pathway analysis, and Gene Set Enrichment Analysis. Immune cell infiltration was analyzed using the CIBERSORT algorithm. RESULTS: Tumor adipocyte infiltration correlated with poor prognosis in GC, leading to the development of a highly accurate and discriminative prognostic prediction model. Key genes, ADH1B, SFRP1, PLAC9, and FABP4, were identified as associated with high adipocyte expression in GC. The diagnostic and prognostic potential of these identified genes was validated using independent datasets. Downregulation of immune cells was observed in GC with high adipocyte expression. CONCLUSION: GC with high intratumoral adipocyte expression demonstrated aggressive tumor biology and a poorer prognosis. The genes ADH1B, SFRP1, PLAC9, and FABP4 have been identified as holding diagnostic and prognostic significance in GC. These findings strongly support the use of adipocyte expression as a valuable indicator of tumor invasiveness and anticipated patient outcomes in GC.

9.
Bioorg Chem ; 151: 107660, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39079391

RESUMO

PD-L1 is expressed in many tumors but rarely in normal tissues, therefore, it can be a target of PET imaging. In this work, we developed new peptide-based PET probes [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p with yields of 20-25 % and 40-55 %, respectively. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p were synthesized within 30 min with high molar activities. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p showed good stability in vivo and in vitro. In vitro cell studies showed [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p target PD-L1 specifically, with high uptake of 61.52 ± 4.39 and 19.29 ± 2.17 %ID/1 million cells in B16F10 cells at 60 min, respectively. Biodistribution results showed that both [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p had lower liver accumulation. In vivo PET imaging results showed that [18F]AlF-PAI-PDL1p had a high tumor uptake of 4.23 ± 0.81 %ID/g at 2 h and increased uptake of 6.60 ± 1.01 %ID/g at 12 h. [68Ga]Ga-PAI-PDL1p also showed high tumor uptake of 2.30 ± 0.20 %ID/g at 2 h and slightly increased uptake of 3.80 ± 0.26 %ID/g at 6 h. In conclusion, [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1 seemed to be potential tracers for PET imaging of PD-L1 expression.

10.
Med Image Anal ; 97: 103276, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39068830

RESUMO

Radiation therapy plays a crucial role in cancer treatment, necessitating precise delivery of radiation to tumors while sparing healthy tissues over multiple days. Computed tomography (CT) is integral for treatment planning, offering electron density data crucial for accurate dose calculations. However, accurately representing patient anatomy is challenging, especially in adaptive radiotherapy, where CT is not acquired daily. Magnetic resonance imaging (MRI) provides superior soft-tissue contrast. Still, it lacks electron density information, while cone beam CT (CBCT) lacks direct electron density calibration and is mainly used for patient positioning. Adopting MRI-only or CBCT-based adaptive radiotherapy eliminates the need for CT planning but presents challenges. Synthetic CT (sCT) generation techniques aim to address these challenges by using image synthesis to bridge the gap between MRI, CBCT, and CT. The SynthRAD2023 challenge was organized to compare synthetic CT generation methods using multi-center ground truth data from 1080 patients, divided into two tasks: (1) MRI-to-CT and (2) CBCT-to-CT. The evaluation included image similarity and dose-based metrics from proton and photon plans. The challenge attracted significant participation, with 617 registrations and 22/17 valid submissions for tasks 1/2. Top-performing teams achieved high structural similarity indices (≥0.87/0.90) and gamma pass rates for photon (≥98.1%/99.0%) and proton (≥97.3%/97.0%) plans. However, no significant correlation was found between image similarity metrics and dose accuracy, emphasizing the need for dose evaluation when assessing the clinical applicability of sCT. SynthRAD2023 facilitated the investigation and benchmarking of sCT generation techniques, providing insights for developing MRI-only and CBCT-based adaptive radiotherapy. It showcased the growing capacity of deep learning to produce high-quality sCT, reducing reliance on conventional CT for treatment planning.

11.
Front Oncol ; 14: 1411731, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974237

RESUMO

Globally, lung cancer stands as the leading type of cancer in terms of incidence and is the major source of mortality attributed to cancer. We have outlined the molecular biomarkers for lung cancer that are available clinically. Circulating tumor cells (CTCs) spread from the original location, circulate in the bloodstream, extravasate, and metastasize, forming secondary tumors by invading and establishing a favorable environment. CTC analysis is considered a common liquid biopsy method for lung cancer. We have enumerated both in vivo and ex vivo techniques for CTC separation and enrichment, examined the advantages and limitations of these methods, and also discussed the detection of CTCs in other bodily fluids. We have evaluated the value of CTCs, as well as CTCs in conjunction with other biomarkers, for their utility in the early detection and prognostic assessment of patients with lung cancer. CTCs engage with diverse cells of the metastatic process, interfering with the interaction between CTCs and various cells in metastasis, potentially halting metastasis and enhancing patient prognosis.

12.
Radiat Oncol ; 19(1): 87, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956690

RESUMO

BACKGROUND AND PURPOSE: Various deep learning auto-segmentation (DLAS) models have been proposed, some of which have been commercialized. However, the issue of performance degradation is notable when pretrained models are deployed in the clinic. This study aims to enhance precision of a popular commercial DLAS product in rectal cancer radiotherapy by localized fine-tuning, addressing challenges in practicality and generalizability in real-world clinical settings. MATERIALS AND METHODS: A total of 120 Stage II/III mid-low rectal cancer patients were retrospectively enrolled and divided into three datasets: training (n = 60), external validation (ExVal, n = 30), and generalizability evaluation (GenEva, n = 30) datasets respectively. The patients in the training and ExVal dataset were acquired on the same CT simulator, while those in GenEva were on a different CT simulator. The commercial DLAS software was first localized fine-tuned (LFT) for clinical target volume (CTV) and organs-at-risk (OAR) using the training data, and then validated on ExVal and GenEva respectively. Performance evaluation involved comparing the LFT model with the vendor-provided pretrained model (VPM) against ground truth contours, using metrics like Dice similarity coefficient (DSC), 95th Hausdorff distance (95HD), sensitivity and specificity. RESULTS: LFT significantly improved CTV delineation accuracy (p < 0.05) with LFT outperforming VPM in target volume, DSC, 95HD and specificity. Both models exhibited adequate accuracy for bladder and femoral heads, and LFT demonstrated significant enhancement in segmenting the more complex small intestine. We did not identify performance degradation when LFT and VPM models were applied in the GenEva dataset. CONCLUSIONS: The necessity and potential benefits of LFT DLAS towards institution-specific model adaption is underscored. The commercial DLAS software exhibits superior accuracy once localized fine-tuned, and is highly robust to imaging equipment changes.


Assuntos
Aprendizado Profundo , Órgãos em Risco , Planejamento da Radioterapia Assistida por Computador , Neoplasias Retais , Humanos , Neoplasias Retais/radioterapia , Neoplasias Retais/patologia , Órgãos em Risco/efeitos da radiação , Estudos Retrospectivos , Planejamento da Radioterapia Assistida por Computador/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X , Adulto , Radioterapia de Intensidade Modulada/métodos
13.
Mol Cell ; 84(15): 2838-2855.e10, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39019045

RESUMO

Despite the unique ability of pioneer factors (PFs) to target nucleosomal sites in closed chromatin, they only bind a small fraction of their genomic motifs. The underlying mechanism of this selectivity is not well understood. Here, we design a high-throughput assay called chromatin immunoprecipitation with integrated synthetic oligonucleotides (ChIP-ISO) to systematically dissect sequence features affecting the binding specificity of a classic PF, FOXA1, in human A549 cells. Combining ChIP-ISO with in vitro and neural network analyses, we find that (1) FOXA1 binding is strongly affected by co-binding transcription factors (TFs) AP-1 and CEBPB; (2) FOXA1 and AP-1 show binding cooperativity in vitro; (3) FOXA1's binding is determined more by local sequences than chromatin context, including eu-/heterochromatin; and (4) AP-1 is partially responsible for differential binding of FOXA1 in different cell types. Our study presents a framework for elucidating genetic rules underlying PF binding specificity and reveals a mechanism for context-specific regulation of its binding.


Assuntos
Fator 3-alfa Nuclear de Hepatócito , Ligação Proteica , Fator de Transcrição AP-1 , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Fator de Transcrição AP-1/metabolismo , Fator de Transcrição AP-1/genética , Sítios de Ligação , Células A549 , Cromatina/metabolismo , Cromatina/genética , Imunoprecipitação da Cromatina , Oligonucleotídeos/metabolismo , Oligonucleotídeos/genética
14.
Sensors (Basel) ; 24(14)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39065890

RESUMO

Azimuth multi-channel synthetic aperture radar (SAR) has always been an important technical means to achieve high-resolution wide-swath (HRWS) SAR imaging. However, in the space-borne azimuth multi-channel SAR system, random phase noise will be produced during the operation of each channel receiver. The phase noise of each channel is superimposed on the SAR echo signal of the corresponding channel, which will cause the phase imbalance between the channels and lead to the generation of false targets. In view of the above problems, this paper proposes a random phase noise compensation method for space-borne azimuth multi-channel SAR. This method performs feature decomposition by calculating the covariance matrix of the echo signal and converts the random phase noise estimation into the optimal solution of the cost function. Considering that the phase noise in the receiver has frequency-dependent and time-varying characteristics, this method calculates the phase noise estimation value corresponding to each range-frequency point in the range direction and obtains the phase noise estimation value by expectation in the azimuth direction. The proposed random phase noise compensation method can suppress false targets well and make the radar present a well-focused SAR image. Finally, the usefulness of the suggested method is verified by simulation experiments.

15.
Foods ; 13(14)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39063287

RESUMO

Previous studies have demonstrated that enzymatically prepared coix seed prolamin hydrolysates (CHPs) contain several bioactive peptides that efficiently inhibit the activity of target enzymes (α-glucosidase and dipeptidyl kinase-IV) in type 2 diabetes mellitus (T2DM). However, the anti-T2DM effects and potential mechanisms of CHPs as a whole in vivo have not yet been systematically explored. Therefore, we evaluated the preventive, therapeutic, and modifying effects of CHPs on T2DM by combining physiological and liver transcriptomics with a T2DM mouse model. The results showed that sustained high-fructose intake led to prediabetic symptoms in mice, with abnormal fluctuations in blood glucose and blood lipid levels. Intervention with CPHs effectively prevented weight loss; regulated abnormal changes in blood glucose; improved impaired glucose tolerance; inhibited the abnormal expression of total cholesterol, triglycerides, and low-density lipoproteins; alleviated insulin resistance; and restored pancreatic islet tissue function in mice fed a high-fructose diet. In addition, we found that CHPs also play a palliative role in the loss of liver function and protect various organ tissues (including the liver, kidneys, pancreas, and heart), and are effective in preventing damage to the liver and pancreatic islet cells. We also found that the intake of CHPs reversed the abnormally altered hepatic gene profile in model mice and identified 381 differentially expressed genes that could serve as key genes for preventing the development of T2DM, which are highly correlated with multiple glycolipid metabolic pathways. We demonstrated that CHPs play a positive role in the normal functioning of the insulin signalling pathway dominated by the IRS-1/PI3K/AKT (insulin receptor substrates-1/phosphoinositide 3-kinase/protein kinase B) pathway. In summary, CHPs can be used as effective food-borne glucose-modifying components of healthy foods.

16.
J Exp Med ; 221(9)2024 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-38935023

RESUMO

Nuclear factor Foxp3 determines regulatory T (Treg) cell fate and function via mechanisms that remain unclear. Here, we investigate the nature of Foxp3-mediated gene regulation in suppressing autoimmunity and antitumor immune response. Contrasting with previous models, we find that Foxp3-chromatin binding is regulated by Treg activation states, tumor microenvironment, and antigen and cytokine stimulations. Proteomics studies uncover dynamic proteins within Foxp3 proximity upon TCR or IL-2 receptor signaling in vitro, reflecting intricate interactions among Foxp3, signal transducers, and chromatin. Pharmacological inhibition and genetic knockdown experiments indicate that NFAT and AP-1 protein Batf are required for enhanced Foxp3-chromatin binding in activated Treg cells and tumor-infiltrating Treg cells to modulate target gene expression. Furthermore, mutations at the Foxp3 DNA-binding domain destabilize the Foxp3-chromatin association. These representative settings delineate context-dependent Foxp3-chromatin interaction, suggesting that Foxp3 associates with chromatin by hijacking DNA-binding proteins resulting from Treg activation or differentiation, which is stabilized by direct Foxp3-DNA binding, to dynamically regulate Treg cell function according to immunological contexts.


Assuntos
Cromatina , Fatores de Transcrição Forkhead , Linfócitos T Reguladores , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Cromatina/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Transdução de Sinais , Ligação Proteica , Humanos , Regulação da Expressão Gênica , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Interleucina-2/metabolismo , Receptores de Interleucina-2/genética , Diferenciação Celular
17.
Chin Med J (Engl) ; 137(14): 1651-1662, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38867424

RESUMO

ABSTRACT: Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.


Assuntos
Artrite , Ferro , Humanos , Ferro/metabolismo , Artrite/metabolismo , Artrite/tratamento farmacológico , Homeostase , Animais
18.
Nanomicro Lett ; 16(1): 228, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935160

RESUMO

Ammonia (NH3) is a carbon-free, hydrogen-rich chemical related to global food safety, clean energy, and environmental protection. As an essential technology for meeting the requirements raised by such issues, NH3 capture has been intensively explored by researchers in both fundamental and applied fields. The four typical methods used are (1) solvent absorption by ionic liquids and their derivatives, (2) adsorption by porous solids, (3) ab-adsorption by porous liquids, and (4) membrane separation. Rooted in the development of advanced materials for NH3 capture, we conducted a coherent review of the design of different materials, mainly in the past 5 years, their interactions with NH3 molecules and construction of transport pathways, as well as the structure-property relationship, with specific examples discussed. Finally, the challenges in current research and future worthwhile directions for NH3 capture materials are proposed.

19.
Nat Commun ; 15(1): 4358, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778058

RESUMO

3C-based methods have significantly advanced our understanding of 3D genome organization. However, it remains a formidable task to precisely capture long-range chromosomal interactions between individual loci, such as those between promoters and distal enhancers. Here, we present Methyltransferase Targeting-based chromosome Architecture Capture (MTAC), a method that maps the contacts between a target site (viewpoint) and the rest of the genome in budding yeast with high resolution and sensitivity. MTAC detects hundreds of intra- and inter-chromosomal interactions within nucleosome-depleted regions (NDRs) that cannot be captured by 4C, Hi-C, or Micro-C. By applying MTAC to various viewpoints, we find that (1) most long-distance chromosomal interactions detected by MTAC reflect tethering by the nuclear pore complexes (NPCs), (2) genes co-regulated by methionine assemble into inter-chromosomal clusters near NPCs upon activation, (3) mediated by condensin, the mating locus forms a highly specific interaction with the recombination enhancer (RE) in a mating-type specific manner, and (4) correlation of MTAC signals among NDRs reveal spatial mixing and segregation of the genome. Overall, these results demonstrate MTAC as a powerful tool to resolve fine-scale long-distance chromosomal interactions and provide insights into the 3D genome organization.


Assuntos
Cromossomos Fúngicos , Metilação de DNA , Nucleossomos , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Nucleossomos/metabolismo , Nucleossomos/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Cromossomos Fúngicos/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Mapeamento Cromossômico/métodos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/genética , Genoma Fúngico , Regiões Promotoras Genéticas/genética , Complexos Multiproteicos/metabolismo , Complexos Multiproteicos/genética , Poro Nuclear/metabolismo , Poro Nuclear/genética , Metiltransferases/metabolismo , Metiltransferases/genética
20.
Diagnostics (Basel) ; 14(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38786343

RESUMO

Circulating cfRNA in plasma has emerged as a fascinating area of research with potential applications in disease diagnosis, monitoring, and personalized medicine. Circulating RNA sequencing technology allows for the non-invasive collection of important information about the expression of target genes, eliminating the need for biopsies. This comprehensive review aims to provide a detailed overview of the current knowledge and advancements in the study of plasma cfRNA, focusing on its diverse landscape and biological functions, detection methods, its diagnostic and prognostic potential in various diseases, challenges, and future perspectives.

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