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1.
Fitoterapia ; 176: 106018, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38744385

RESUMO

An extensive phytochemical investigation on the rare medicinal plant Semiliquidambar cathayensis (family: Hamamelidaceae) led to the isolation of four new (1-4, named semiliquidacids A-D, respectively) and 25 related known pentacyclic triterpenoids. The new structures with absolute configurations were elucidated by spectroscopic methods, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compound 1 represents the first naturally occurring ursane-type triterpenoid featuring an uncommon C-25 formyl group. Compound 4 and oleanolic acid (13) exhibited remarkable inhibitory effects against the ATP-citrate lyase (ACL, an emerging drug target for hyperlipidemia and related metabolic disorders) with IC50 values of 6.5 and 11.9 µM, respectively. The molecular interaction and binding mode between the bioactive triterpenoids and ACL were elaborated by conducting a molecular docking study. Meanwhile, the chemotaxonomic significance of the isolated triterpenoids has been briefly discussed.

2.
Int J Hyperthermia ; 41(1): 2335201, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38583875

RESUMO

PURPOSE: Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PCa to RT and investigate the underlying molecular mechanisms. METHODS: We developed a dedicated MW-HT heating setup, created an in vitro and in vivo MW-HT + RT treatment model for CRPC. We evaluated PC3 cell proliferation using CCK-8, colony experiments, DAPI staining, comet assay and ROS detection method. We also monitored nude mouse models of PCa during treatment, measured tumor weight, and calculated the tumor inhibition rate. Western blotting was used to detect DNA damage repair protein expression in PC3 cells and transplanted tumors. RESULTS: Compared to control, PC3 cell survival and clone formation rates decreased in RT + MW-HT group, demonstrating significant increase in apoptosis, ROS levels, and DNA damage. Lower tumor volumes and weights were observed in treatment groups. Ki-67 expression level was reduced in all treatment groups, with significant decrease in RT + MW-HT groups. The most significant apoptosis induction was confirmed in RT + MW-HT group by TUNEL staining. Protein expression levels of DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways significantly decreased in RT + MW-HT groups. CONCLUSION: MW-HT + RT treatment significantly inhibited DNA damage repair by downregulating DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways, leading to increased ROS levels, aggravate DNA damage, apoptosis, and necrosis in PC3 cells, a well-established model of CRPC.


Assuntos
Adenocarcinoma , Hipertermia Induzida , Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Humanos , Masculino , Animais , Camundongos , Neoplasias de Próstata Resistentes à Castração/radioterapia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Células PC-3 , Espécies Reativas de Oxigênio/metabolismo , Micro-Ondas , Proteína Supressora de Tumor p53/metabolismo , Hipertermia Induzida/métodos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/metabolismo , Reparo do DNA , Apoptose , Estresse Oxidativo , Hipertermia , Adenocarcinoma/radioterapia , DNA/metabolismo , Linhagem Celular Tumoral , Proliferação de Células
3.
PeerJ Comput Sci ; 10: e1844, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660146

RESUMO

With the rapid development of societal information, electronic educational resources have become an indispensable component of modern education. In response to the increasingly formidable challenges faced by secondary school teachers, this study endeavors to analyze and explore the application of artificial intelligence (AI) methods to enhance their cognitive literacy. Initially, this discourse delves into the application of AI-generated electronic images in the training and instruction of middle school educators, subjecting it to thorough analysis. Emphasis is placed on elucidating the pivotal role played by AI electronic images in elevating the proficiency of middle school teachers. Subsequently, an integrated intelligent device serves as the foundation for establishing a model that applies intelligent classification and algorithms based on the Structure of the Observed Learning Outcome (SOLO). This model is designed to assess the cognitive literacy and teaching efficacy of middle school educators, and its performance is juxtaposed with classification algorithms such as support vector machine (SVM) and decision trees. The findings reveal that, following 600 iterations of the model, the SVM algorithm achieves a 77% accuracy rate in recognizing teacher literacy, whereas the SOLO algorithm attains 80%. Concurrently, the spatial complexities of the SVM-based and SOLO-based intelligent literacy improvement models are determined to be 45 and 22, respectively. Notably, it is discerned that, with escalating iterations, the SOLO algorithm exhibits higher accuracy and reduced spatial complexity in evaluating teachers' pedagogical literacy. Consequently, the utilization of AI methodologies proves highly efficacious in advancing electronic imaging technology and enhancing the efficacy of image recognition in educational instruction.

4.
Int Immunopharmacol ; 130: 111728, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38430801

RESUMO

The treatment of hepatocellular carcinoma (HCC) remains a major challenge in the medical field. Lenvatinib, a multi-target tyrosine kinase inhibitor, has demonstrated anti-HCC effects by targeting and inhibiting pathways such as vascular endothelial growth factor receptor 1-3 (VEGFR1-3). However, the therapeutic efficacy of Lenvatinib is subject to various influences, with the hypoxic microenvironment of the tumor being a pivotal factor. Consequently, altering the hypoxic milieu of the tumor emerges as a viable strategy to augment the efficacy of Lenvatinib. Hypoxia-inducible factor-1α (HIF-1α), synthesized by tumor cells in response to oxygen-deprived conditions, regulates the expression of resistance genes, promotes tumor angiogenesis and cell proliferation, enhances tumor cell invasion, and confers resistance to radiotherapy and chemotherapy. Thus, we constructed a self-designed siRNA targeting HIF-1α to suppress its expression and improve the efficacy of Lenvatinib in treating HCC. The therapeutic efficacy of siRNA-HIF-1α in combination with Lenvatinib on HCC were evaluated through in vivo and in vitro experiments. The results showed that the recombinant Salmonella delivering siRNA-HIF-1α in combination with Lenvatinib effectively inhibited tumor growth and prolonged the survival of tumor-bearing mice. This treatment approach reduced cell proliferation and angiogenesis in HCC tissues while promoting tumor cell apoptosis. Additionally, this combined therapy significantly increased the infiltration of T lymphocytes and M1 macrophages within the tumor microenvironment, as well as elevated the proportion of immune cells in the spleen, thereby potentiating the host's immune response against the tumor.


Assuntos
Carcinoma Hepatocelular , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , RNA Interferente Pequeno , Terapêutica com RNAi , Salmonella , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/uso terapêutico , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Terapia Combinada , Terapêutica com RNAi/métodos
5.
Int J Mol Sci ; 25(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38474195

RESUMO

Neuroblastoma (NB) is one of the highly vascularized childhood solid tumors, and understanding the molecular mechanisms underlying angiogenesis in NB is crucial for developing effective therapeutic strategies. B-cell receptor-associated protein 31 (BAP31) has been implicated in tumor progression, but its role in angiogenesis remains unexplored. This study investigated BAP31 modulation of pro-angiogenic factors in SH-SY5Y NB cells. Through protein overexpression, knockdown, antibody blocking, and quantification experiments, we demonstrated that overexpression of BAP31 led to increased levels of vascular endothelial growth factor A (VEGFA) and Galectin-3 (GAL-3), which are known to promote angiogenesis. Conditioned medium derived from BAP31-overexpressing neuroblastoma cells stimulated migration and tube formation in endothelial cells, indicating its pro-angiogenic properties. Also, we demonstrated that BAP31 enhances capillary tube formation by regulating hypoxia-inducible factor 1 alpha (HIF-1α) and its downstream target, GAL-3. Furthermore, GAL-3 downstream proteins, Jagged 1 and VEGF receptor 2 (VEGFR2), were up-regulated, and blocking GAL-3 partially inhibited the BAP31-induced tube formation. These findings suggest that BAP31 promotes angiogenesis in NB by modulating GAL-3 and VEGF signaling, thereby shaping the tumor microenvironment. This study provides novel insights into the pro-angiogenic role of BAP31 in NB.


Assuntos
Neuroblastoma , Fator A de Crescimento do Endotélio Vascular , Criança , Humanos , Angiogênese , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Galectina 3/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neovascularização Patológica/patologia , Neuroblastoma/metabolismo , Microambiente Tumoral , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Adv Biol (Weinh) ; 8(4): e2300534, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38314942

RESUMO

N6-methyladenosine (m6A) modification is involved in many aspects of gastric cancer (GC). Moreover, m6A and glycolysis-related genes (GRGs) play important roles in immunotherapeutic and prognostic implication of GC. However, GRGs involved in m6A regulation have never been analyzed comprehensively in GC. Herein, the study aims to identify and validate a novel signature based on m6A-related GRGs in GC patients. Therefore, a m6A-related GRGs signature is established, which can predict the survival of patients with GC and remain an independent prognostic factor in multivariate analyses. Clinical significance of the model is well validated in internal cohort and independent validation cohort. In addition, the expression levels of risk model-related GRGs in clinical samples are validated. Consistent with the database results, all model genes are up-regulated in expression except DCN. After regrouping the patients based on this risk model, the study can effectively distinguish between them in respect to immune-cell infiltration microenvironment and immunotherapeutic response. Additionally, candidate drugs targeting risk model-related GRGs are confirmed. Finally, a nomogram combining risk scores and clinical parameters is created, and calibration plots show that the nomogram can accurately predict survival. This risk model can serve as a reliable assessment tool for predicting prognosis and immunotherapeutic responses in GC patients.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Prognóstico , Genes Reguladores , Nomogramas , Imunoterapia , Microambiente Tumoral/genética
7.
Sci Rep ; 14(1): 2888, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38311606

RESUMO

This work aims to investigate the application of advanced deep learning algorithms and image recognition technologies to enhance language analysis tools in secondary education, with the goal of providing educators with more effective resources and support. Based on artificial intelligence, this work integrates data mining techniques related to deep learning to analyze and study language behavior in secondary school education. Initially, a framework for analyzing language behavior in secondary school education is constructed. This involves evaluating the current state of language behavior, establishing a framework based on evaluation comments, and defining indicators for analyzing language behavior in online secondary school education. Subsequently, data mining technology and image and character recognition technology are employed to conduct data mining for online courses in secondary schools, encompassing the processing of teaching video images and character recognition. Finally, an experiment is designed to validate the proposed framework for analyzing language behavior in secondary school education. The results indicate specific differences among the grouped evaluation scores for each analysis indicator. The significance p values for the online classroom discourse's speaking rate, speech intelligibility, average sentence length, and content similarity are -0.56, -0.71, -0.71, and -0.74, respectively. The aim is to identify the most effective teaching behaviors for learners and enhance the support for online course instruction.


Assuntos
Inteligência Artificial , Aprendizado Profundo , Instituições Acadêmicas , Idioma , Tecnologia
8.
Br J Ophthalmol ; 108(3): 432-439, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36596660

RESUMO

BACKGROUND: Optical coherence tomography angiography (OCTA) enables fast and non-invasive high-resolution imaging of retinal microvasculature and is suggested as a potential tool in the early detection of retinal microvascular changes in Alzheimer's Disease (AD). We developed a standardised OCTA analysis framework and compared their extracted parameters among controls and AD/mild cognitive impairment (MCI) in a cross-section study. METHODS: We defined and extracted geometrical parameters of retinal microvasculature at different retinal layers and in the foveal avascular zone (FAZ) from segmented OCTA images obtained using well-validated state-of-the-art deep learning models. We studied these parameters in 158 subjects (62 healthy control, 55 AD and 41 MCI) using logistic regression to determine their potential in predicting the status of our subjects. RESULTS: In the AD group, there was a significant decrease in vessel area and length densities in the inner vascular complexes (IVC) compared with controls. The number of vascular bifurcations in AD is also significantly lower than that of healthy people. The MCI group demonstrated a decrease in vascular area, length densities, vascular fractal dimension and the number of bifurcations in both the superficial vascular complexes (SVC) and the IVC compared with controls. A larger vascular tortuosity in the IVC, and a larger roundness of FAZ in the SVC, can also be observed in MCI compared with controls. CONCLUSION: Our study demonstrates the applicability of OCTA for the diagnosis of AD and MCI, and provides a standard tool for future clinical service and research. Biomarkers from retinal OCTA images can provide useful information for clinical decision-making and diagnosis of AD and MCI.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Angiofluoresceinografia/métodos , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Doença de Alzheimer/diagnóstico por imagem , Microvasos/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem
9.
Phytochemistry ; 218: 113956, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38135206

RESUMO

Seventeen undescribed sesquiterpene-alkaloid hybrids (liriogerphines E-U, 1-17) were isolated and identified during a further phytochemical investigation on the branches and leaves of Chinese tulip tree (Liriodendron chinense), a rare medicinal and ornamental plant endemic to China. These unique heterodimers are conjugates of germacranolide-type sesquiterpenoids with structurally diverse alkaloids [i.e., aporphine- (1-15), proaporphine- (16), and benzyltetrahydroisoquinoline-type (17)] via the formation of a C-N bond. The previously undescribed structures were elucidated by comprehensive spectroscopic data analyses and electronic circular dichroism calculations. Such a class of sesquiterpene-alkaloid hybrids presumably biosynthesized via an aza-Michael addition is quite rare from terrestrial plants. In particular, the sesquiterpene-benzyltetrahydroisoquinoline hybrid skeleton has never been reported until the present study. All the isolates were evaluated for their cytotoxic effects against a small panel of leukemia cell lines (Raji, Jeko-1, Daudi, Jurkat, MV-4-11 and HL-60), and some of them exhibited considerable activities.


Assuntos
Alcaloides , Antineoplásicos , Liriodendron , Sesquiterpenos , Liriodendron/química , Alcaloides/química , Folhas de Planta/química , Sesquiterpenos/química , Estrutura Molecular
10.
Int J Mol Sci ; 24(23)2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38069061

RESUMO

Dysregulated B cell receptor-associated protein 31 (BAP31) plays a crucial role in tumor progression. This study aimed to investigate the functions and molecular mechanism of BAP31 on the miR-206/133b cluster in colorectal cancer (CRC). qPCR was conducted to detect miRNA and mRNA levels in tissues and cells. Western blot assays were used to assess the levels of biomarkers and targets, as well as the levels of BAP31 and HOXD10. Wound healing, coculture and transwell assays were conducted to assess the transendothelial migration abilities of CRC cells. A luciferase assay was employed to assess miRNA binding effects on targets, as well as the initiating transcription effect of genomic fragments. Tumor growth and lung metastatic models were established through an in vivo animal study. BAP31 overexpression in CRC cells led to a reduction in the expression of the miR-206/133b cluster. The expression of the miR-206/133b cluster was correlated with the transendothelial migration capability of CRC cells. The miR-206/133b cluster was found to directly regulate cell division cycle 42 (CDC42) and actin-related protein 2/3 complex subunit 5 (ARPC5) in the tight junction pathway (hsa04530). Moreover, a potential transcription regulator of the miR-206/133b cluster was also found to be Homeobox D10 (HOXD10). We further elucidated the molecular mechanisms and functional mechanisms of BAP31's regulatory role in the expression levels of the miR-206/133b cluster by inhibiting HOXD10 translocation from the cytoplasm to the nucleus. In conclusion, this study provides valuable insights into how BAP31 regulates the transcription of the miR-206/133b cluster and how BAP31-related lung metastases arise in CRC.


Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , MicroRNAs , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Migração Transendotelial e Transepitelial
11.
ACS Appl Mater Interfaces ; 15(51): 59681-59692, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38086762

RESUMO

In the field of electromagnetic wave (EMW) absorption, carbon matrix materials based on metal-organic frameworks (MOFs) have drawn more interest as a result of their outstanding advantages, such as porous structure, lightweight, controlled morphology, etc. However, how to broaden the effective absorption bandwidth [EAB; reflection loss (RL) ≤ -10 dB] is still a challenge. In this paper, large microsphere structures of a Co/C composite composed of small particle clusters were successfully prepared by the solvothermal method and annealing treatment. At a filling ratio of 40 wt %, the Co/C composite shows attractive microwave absorption (MA) performance after being annealed at 600 °C in an atmosphere of argon. With an EAB of 6.32 GHz (9.92-16.24 GHz) and a thickness of just 2.57 mm, the minimum RL can be attained at -54.55 dB. Most importantly, the EAB can attain 7.12 GHz (10.88-18.0 GHz) when the thickness is 2.38 mm, which is larger than that of the majority of MOF-derived composites. The superior MA performance is strongly related to excellent impedance matching and a higher attenuation constant. This study provides a simple strategy for synthesizing a MOF-derived Co/C composite with a wide EAB.

12.
Artigo em Inglês | MEDLINE | ID: mdl-37998307

RESUMO

Psychosocial support programs have been increasingly implemented to protect asylum seekers' wellbeing, though how and why these interventions work is not yet fully understood. This study first uses questionnaires to examine how self-efficacy, satisfaction of basic psychological needs, and adaptive stress may influence wellbeing for a group of asylum-seeking mothers attending a community-based psychosocial program called Welcome Haven. Second, we explore mothers' experiences attending the Welcome Haven program through qualitative interviews. Analysis reveals the importance of relatedness as a predictor of wellbeing as well as the mediating role of adaptive stress between need satisfaction and wellbeing. Further, attending Welcome Haven is associated with reduced adaptive stress and increased wellbeing, which correspond with the thematic analysis showing that attendance at the workshops fostered a sense of belonging through connection with other asylum seekers and service providers as well as empowerment through access to information and self-expression. The results point to the importance of community-based support that addresses adaptive stress and the promotion of social connection as key determinants of wellbeing. Nonetheless, the centrality of pervasive structural stressors asylum seekers experience during resettlement also cautions that relief offered by interventions may be insufficient in the face of ongoing systemic inequality and marginalization.


Assuntos
Mães , Refugiados , Feminino , Humanos , Pesquisa Qualitativa , Inquéritos e Questionários , Refugiados/psicologia , Autonomia Pessoal
13.
Chem Commun (Camb) ; 59(97): 14431-14434, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37982153

RESUMO

Rhodium-catalyzed three-component C-H bond activation of aromatics with amides and aldehydes to synthesize amines was established. The addition of copper was found to be essential to ensure the high reactivity. The mechanistic studies indicated that key intermediates formed by the transmetallization between rhodium and copper could further promote the addition between 2-(pyridin-2-yl)-phenyl-metal species and imines. A series of densely substituted amines could be conveniently prepared by this one-step, three-component procedure from commercially available substrates via C-H bond activation with water as the only by-product.

14.
Res Sq ; 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37790337

RESUMO

Matrix stiffness and corresponding mechano-signaling play indispensable roles in cellular phenotypes and functions. How tissue stiffness influences the behavior of monocytes, a major circulating leukocyte of the innate system, and how it may promote the emergence of collective cell behavior is less understood. Here, using tunable collagen-coated hydrogels of physiological stiffness, we show that human primary monocytes undergo a dynamic local phase separation to form highly regular, reversible, multicellular, multi-layered domains on soft matrix. Local activation of the ß2 integrin initiates inter-cellular adhesion, while global soluble inhibitory factors maintain the steady state domain pattern over days. Patterned domain formation generated by monocytes is unique among other key immune cells, including macrophages, B cells, T cells, and NK cells. While inhibiting their phagocytic capability, domain formation promotes monocytes' survival. We develop a computational model based on the Cahn-Hilliard equation of phase separation, combined with a Turing mechanism of local activation and global inhibition suggested by our experiments, and provides experimentally validated predictions of the role of seeding density and both chemotactic and random cell migration on domain pattern formation. This work reveals that, unlike active matters, cells can generate complex cell phases by exploiting their mechanosensing abilities and combined short-range interactions and long-range signals to enhance their survival.

15.
bioRxiv ; 2023 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-37790420

RESUMO

Aneuploidy, a near ubiquitous genetic feature of tumors, is a context-dependent driver of cancer evolution; however, the mechanistic basis of this role remains unclear. Here, by inducing heterogeneous aneuploidy in non-transformed human colon organoids (colonoids), we investigate how the effects of aneuploidy on cell growth and differentiation may promote malignant transformation. Single-cell RNA sequencing reveals that the gene expression signature across over 100 unique aneuploid karyotypes is enriched with p53 responsive genes. The primary driver of p53 activation is karyotype complexity. Complex aneuploid cells with multiple unbalanced chromosomes activate p53 and undergo G1 cell-cycle arrest, independent of DNA damage and without evidence of senescence. By contrast, simple aneuploid cells with 1-3 chromosomes gained or lost continue to proliferate, demonstrated by single cell tracking in colonoids. Notably, simple aneuploid cells exhibit impaired differentiation when niche factors are withdrawn. These findings suggest that while complex aneuploid cells are eliminated from the normal epithelium due to p53 activation, simple aneuploid cells can escape this checkpoint and may contribute to niche factor-independent growth of cancer-initiating cells.

16.
bioRxiv ; 2023 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-37693593

RESUMO

The regulation of mammalian cell volume is crucial for maintaining key cellular processes. Cells can rapidly respond to osmotic and hydrostatic pressure imbalances during environmental challenges, generating fluxes of water and ions that alter volume within minutes. While the role of ion pump and leak in cell volume regulation has been well-established, the role of the actomyosin cytoskeleton and its substantial interplay with ion transporters are still unclear. In this work, we discover a system of cell volume regulation controlled by cytoskeletal activation of ion transporters. Under hypotonic shock, NIH-3T3 and MCF-10A display a 20% secondary volume increase (SVI) following the initial regulatory volume decrease. We show that SVI is initiated by Ca 2+ influx through stretch activated channel Piezo1 and subsequent actomyosin remodeling. Rather than contracting cells, actomyosin triggers cell swelling by activating Na + -H + exchanger 1 (NHE1) through their co-binding partner ezrin. Cytoskeletal activation of NHE1 can be similarly triggered by mechanical stretch and attenuated by soft substrates. This mechanism is absent in certain cancer cell lines such as HT1080 and MDA-MB-231, where volume regulation is dominated by intrinsic response of ion transporters. Moreover, cytoskeletal activation of NHE1 during SVI induces nuclear deformation, leading to DNA demethylation and a significant, immediate transcriptomic response in 3T3 cells, a phenomenon that is absent in HT1080 cells. Overall, our findings reveal the central role of Ca 2+ and actomyosin-mediated mechanosensation in the regulation of ion transport, cell volume, DNA methylation, and transcriptomics.

17.
Front Immunol ; 14: 1152899, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37559719

RESUMO

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly pathogenic to humans and has caused the ongoing coronavirus disease 2019 (COVID-19) pandemic. Vaccines are one of the efficient ways to prevent the viral infection. After COVID-19 vaccination, the monitoring of the dynamic change in neutralizing antibodies is necessary to determine booster requirements. Methods: We estimated the effectiveness of the inactivated vaccines by monitoring dynamic SARS-CoV-2 neutralizing antibodies for over 2 years. Additionally, we also investigated the activation of T lymphocytes (CD3+ T cells) after three doses of the inactivated vaccine. Result: The results showed that the rate of reduction of SARS-CoV-2 neutralizing antibody levels gradually showed after each booster dose. The IgG/IgM level at 9 months after the third vaccination were significantly higher than those at 6 months after the second dose (p<0.0001). The expression of CD25+T cell in 18-35 age group was significantly higher than that in the other groups. Nine months after the third dose (the time of last blood sample collection), the expression of CD25+T cell in the 18-35 age group was significantly higher than that at 6 months after the second dose. CD25+T cell in the 18-35 years old group was significantly higher than 6 months after the second vaccination. Conclusion: CD25, a late activation marker of lymphocytes and high-activity memory T cell subgroup, exhibited higher levels at the later stages after vaccination. COVID-19 booster vaccination in older adults and regular testing of SARS-CoV-2 neutralizing antibodies are recommended. Booster doses should be administered if the antibody level falls below the 30% inhibition rate.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Idoso , Lactente , Adolescente , Adulto Jovem , Adulto , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas de Produtos Inativados/efeitos adversos
18.
bioRxiv ; 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37546904

RESUMO

Matrix stiffness and corresponding mechano-signaling play indispensable roles in cellular phenotypes and functions. How tissue stiffness influences the behavior of monocytes, a major circulating leukocyte of the innate system, and how it may promote the emergence of collective cell behavior is less understood. Here, using tunable collagen-coated hydrogels of physiological stiffness, we show that human primary monocytes undergo a dynamic local phase separation to form highly patterned multicellular multi-layered domains on soft matrix. Local activation of the ß2 integrin initiates inter-cellular adhesion, while global soluble inhibitory factors maintain the steady-state domain pattern over days. Patterned domain formation generated by monocytes is unique among other key immune cells, including macrophages, B cells, T cells, and NK cells. While inhibiting their phagocytic capability, domain formation promotes monocytes' survival. We develop a computational model based on the Cahn-Hilliard equation, which includes combined local activation and global inhibition mechanisms of intercellular adhesion suggested by our experiments, and provides experimentally validated predictions of the role of seeding density and both chemotactic and random cell migration on pattern formation.

19.
Sci Total Environ ; 902: 166115, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37572893

RESUMO

The typical aromatic and phenolic pollutant, p-nitrophenol (PNP), is extensively used in the industry and can seriously threaten the environmental health. Biochar, as a solid carbon-rich material, can directly degrade PNP. It has been reported that the PNP degradation by biochar is closely related to the electron exchange capacity of biochar (the sum of electron donating and accepting capacities). However, the roles of electron donating and accepting capacity of biochar in PNP degradation have not been distinguished before. In this study, the biochar samples were chemically modified to manipulate the electron donating and accepting capacities of biochar samples. Compared with pristine biochar (3.67 %), modified biochar had higher degradation efficiencies of PNP (>7.81 %). The strictly positive correlation between the electron donating capacities and the PNP degradation rates of biochar samples (r = 0.98, p < 0.05) indicated that the PNP degradation process by biochar is dominated by the reduction process. Although both the oxidation and reduction degradation products were found in the degradation system, the quenching experiment of OH, a key radical in the process of oxidation degradation, further proved that the oxidation process just played a minor role (<10 %) in the PNP degradation by biochar. This study shed light on the degradation mechanism of PNP by biochar and could promote the application of biochar in the pollution remediation.


Assuntos
Carvão Vegetal , Elétrons , Carbono
20.
Biophys J ; 122(16): 3354-3368, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37475215

RESUMO

Tissue cells in epithelial or endothelial monolayers are connected through cell-cell junctions, which are stabilized by transmembrane E-cadherin bonds and intracellular actin filaments. These bonds and junctions play a crucial role in maintaining the barrier function of epithelia and endothelia and are believed to transmit forces between cells. Additionally, E-cadherin bonds can impact the shape of cell-cell junctions. In this study, we develop a continuum mechanical model of the cell-cell junction by explicitly incorporating the cell membrane, distributions of E-cadherin bonds, cytoplasmic fluid pressure, and F-actin dynamics. The static force-balanced version of the model is able to analyze the influences of cell cortical tension, actin dynamics, and cytoplasmic pressure on the junction shape and E-cadherin bonds. Furthermore, an extended model that incorporates fluid flow, across the cell boundary as well as around the cell, is also examined. This model can couple cell-shape changes with cell cortical tension and fluid flow, and predicts the additional effect of fluid motion on cell-cell junction mechanics. Taken together, our models serve as an intermediate link between molecular-scale models of cell-junction molecules and cell-scale models of tissue and epithelia.


Assuntos
Caderinas , Junções Intercelulares , Junções Intercelulares/metabolismo , Caderinas/metabolismo , Actinas/metabolismo , Membrana Celular/metabolismo , Citoesqueleto de Actina/metabolismo
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