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1.
Stem Cells ; 42(10): 861-873, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39169713

RESUMO

Human dental pulp stem cells (HDPSCs) showed an age-dependent decline in proliferation and differentiation capacity. Decline in proliferation and differentiation capacity affects the dental stromal tissue homeostasis and impairs the regenerative capability of HDPSCs. However, which age-correlated proteins regulate the senescence of HDPSCs remain unknown. Our study investigated the proteomic characteristics of HDPSCs isolated from subjects of different ages and explored the molecular mechanism of age-related changes in HDPSCs. Our study showed that the proliferation and osteogenic differentiation of HDPSCs were decreased, while the expression of aging-related genes (p21, p53) and proportion of senescence-associated ß-galactosidase (SA-ß-gal)-positive cells were increased with aging. The bioinformatic analysis identified that significant proteins positively correlated with age were enriched in response to the mammalian target of rapamycin (mTOR) signaling pathway (ILK, MAPK3, mTOR, STAT1, and STAT3). We demonstrated that OSU-T315, an inhibitor of integrin-linked kinase (ILK), rejuvenated aged HDPSCs, similar to rapamycin (an inhibitor of mTOR). Treatment with OSU-T315 decreased the expression of aging-related genes (p21, p53) and proportion of SA-ß-gal-positive cells in HDPSCs isolated from old (O-HDPSCs). Additionally, OSU-T315 promoted the osteoblastic differentiation capacity of O-HDPSCs in vitro and bone regeneration of O-HDPSCs in rat calvarial bone defects model. Our study indicated that the proliferation and osteoblastic differentiation of HDPSCs were impaired with aging. Notably, the ILK/AKT/mTOR/STAT1 signaling pathway may be a major factor in the regulation of HDPSC senescence, which help to provide interventions for HDPSC senescence.


Assuntos
Diferenciação Celular , Senescência Celular , Polpa Dentária , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Células-Tronco , Serina-Treonina Quinases TOR , Polpa Dentária/citologia , Polpa Dentária/metabolismo , Humanos , Senescência Celular/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Células-Tronco/metabolismo , Células-Tronco/citologia , Diferenciação Celular/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Adolescente , Adulto , Animais , Proliferação de Células/efeitos dos fármacos , Adulto Jovem , Ratos , Masculino , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Criança
2.
BMC Plant Biol ; 24(1): 807, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39187785

RESUMO

Cadmium (Cd) is a biologically non-essential heavy metal, a major soil pollutant, and extremely harmful to plants. The phytohormone methyl jasmonate (MeJA) plays an important role in plant heavy-metal resistance. However, the understanding of the effects of MeJA supply level on alleviating Cd toxicity in plants is limited. Here, we investigated how MeJA regulated the development of physiological processes and cell wall modification in Cosmos bipinnatus. We found that low concentrations of MeJA increased the dry weight of seedlings under 120 µM Cd stress by reducing the transport of Cd from roots to shoots. Moreover, a threshold concentration of exogenous MeJA increased the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in plant roots, the concentration of Cd in the root cell wall, and the contents of pectin and hemicellulose 1 polysaccharides, through converting Cd into pectin-bound forms. These results suggested that MeJA mitigated Cd toxicity by modulating root cell wall polysaccharide and functional group composition, especially through pectin polysaccharides binding to Cd, with effects on Cd transport capacity, specific chemical forms of Cd, and homeostatic antioxidant systems in C. bipinnatus.


Assuntos
Acetatos , Cádmio , Ciclopentanos , Oxilipinas , Reguladores de Crescimento de Plantas , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Acetatos/farmacologia , Cádmio/toxicidade , Reguladores de Crescimento de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Poluentes do Solo/toxicidade , Parede Celular/metabolismo , Parede Celular/efeitos dos fármacos , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Antioxidantes/metabolismo , Superóxido Dismutase/metabolismo
3.
Small ; : e2402954, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39246215

RESUMO

The creation and enhancement of non-precious metal bifunctional catalysts with superior stability and stabilizing activity is necessary to achieve water splitting in alkaline media. The paper presents a method for preparing nickel-cobalt bimetallic selenides (NiCo-Sex/CF) using a combination of hydrothermal and high-temperature selenization techniques. NiCo-Sex/CF shows great potential as a catalyst for water separation. The catalyst's electronic structure and active centre can be modified by double doping with sulfur and selenium, resulting in increased selectivity and activity under varying reaction conditions. This method also offers the benefits of a simple preparation process and applicability to a wide range of catalytic reactions. Experimental results demonstrate that an overpotential of 194 mV produces a current density of 10 mA cm-2 when using this electrocatalyst as an OER catalyst. When used as a HER catalyst, the electrocatalyst required an overpotential of only 76 mV to generate a current density of 10 mA cm-2.Furthermore, a voltage of 1.5 V can drive the overall decomposition of water to achieve a current density of 10 mA cm-2. This study highlights the potential of sulfur-selenide double-doped catalysts for both scientific research and practical applications.

4.
Plant Cell Environ ; 47(11): 4071-4085, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38884189

RESUMO

The identification of new genes involved in regulating cold tolerance in rice is urgent because low temperatures repress plant growth and reduce yields. Cold tolerance is controlled by multiple loci and involves a complex regulatory network. Here, we show that rice jacalin-related lectin (OsJRL) modulates cold tolerance in rice. The loss of OsJRL gene functions increased phenylalanine metabolism and flavonoid biosynthesis under cold stress. The OsJRL knock-out (KO) lines had higher phenylalanine ammonia-lyase (PAL) activity and greater flavonoid accumulation than the wild-type rice, Nipponbare (NIP), under cold stress. The leaves had lower levels of reactive oxygen species (ROS) and showed significantly enhanced cold tolerance compared to NIP. In contrast, the OsJRL overexpression (OE) lines had higher levels of ROS accumulation and showed lower cold tolerance than NIP. Additionally, the OsJRL KO lines accumulated more abscisic acid (ABA) and jasmonic acid (JA) under cold stress than NIP. The OsJRL OE lines showed increased sensitivity to ABA compared to NIP. We conclude that OsJRL negatively regulates the cold tolerance of rice via modulation of phenylalanine metabolism and flavonoid biosynthesis.


Assuntos
Temperatura Baixa , Flavonoides , Regulação da Expressão Gênica de Plantas , Oryza , Fenilalanina , Proteínas de Plantas , Espécies Reativas de Oxigênio , Oryza/genética , Oryza/fisiologia , Oryza/metabolismo , Flavonoides/metabolismo , Flavonoides/biossíntese , Fenilalanina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Oxilipinas/metabolismo , Ácido Abscísico/metabolismo , Fenilalanina Amônia-Liase/metabolismo , Fenilalanina Amônia-Liase/genética , Ciclopentanos/metabolismo , Plantas Geneticamente Modificadas , Folhas de Planta/metabolismo , Folhas de Planta/fisiologia
5.
Cancer Cell Int ; 24(1): 252, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030557

RESUMO

Dysregulated gene expression and imbalance of transcriptional regulation are typical features of cancer. RNA always plays a key role in these processes. Human transcripts contain many RNAs without long open reading frames (ORF, > 100 aa) and that are more than 200 bp in length. They are usually regarded as long non-coding RNA (lncRNA) which play an important role in cancer regulation, including chromatin remodeling, transcriptional regulation, translational regulation and as miRNA sponges. With the advancement of ribosome profiling and sequencing technologies, increasing research evidence revealed that some ORFs in lncRNA can also encode peptides and participate in the regulation of multiple organ tumors, which undoubtedly opens a new chapter in the field of lncRNA and oncology research. In this review, we discuss the biological function of lncRNA in tumors, the current methods to evaluate their coding potential and the role of functional small peptides encoded by lncRNA in cancers. Investigating the small peptides encoded by lncRNA and understanding the regulatory mechanisms of these functional peptides may contribute to a deeper understanding of cancer and the development of new targeted anticancer therapies.

6.
Theor Appl Genet ; 137(2): 35, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38286845

RESUMO

KEY MESSAGE: Powdery mildew resistance gene PmXNM, originated from the Chinese wheat landrace Xiaonanmai, was delimited to a 300.7-kb interval enriched with resistance genes. Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease threatening the yield and quality of wheat worldwide. The use of broad-spectrum disease resistance genes from wheat landraces is an effective strategy to prevent this pathogen. Chinese wheat landrace Xiaonanmai (XNM) was immune to 23 tested Bgt isolates at the seedling stage. The F1, F2, and F2:4 progenies derived from the cross between XNM and Chinese Spring (CS) were used in this study. Genetic analysis revealed that powdery mildew resistance in XNM was controlled by a single dominant gene, temporarily designated PmXNM. Bulked segregant analysis and molecular mapping delimited PmXNM to the distal terminal region of chromosome 4AL flanked by markers caps213923 and kasp511718. The region carrying the PmXNM locus was approximately 300.7 kb and contained nine high-confidence genes according to the reference genome sequence of CS. Five of these genes, annotated as disease resistance RPP13-like proteins 1, were clustered in the target region. Haplotype analysis using the candidate gene-specific markers indicated that the majority of 267 common wheat accessions (75.3%) exhibited extensive gene losses at the PmXNM locus, as confirmed by aligning the targeted genome sequences of CS with those of other sequenced wheat cultivars. Seven candidate gene-specific markers have proven effective for marker-assisted introgression of PmXNM into modern elite cultivars.


Assuntos
Ascomicetos , Triticum , Mapeamento Cromossômico , Triticum/genética , Resistência à Doença/genética , Marcadores Genéticos , Genes de Plantas , Doenças das Plantas/genética
7.
Gerontology ; 70(8): 812-822, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38679016

RESUMO

INTRODUCTION: There is inconsistent evidence on the associations between high-density lipoprotein cholesterol (HDL-C) and risk of sarcopenia. The aim of the study was to determine the evidence existing between HDL-C and sarcopenia in Chinese middle-aged and older adults. METHODS: We used a panel study design of the China Health and Retirement Longitudinal Study (CHARLS), with 7,415 participants (mean age 57.5 years) from 2011, 2013, and 2015. HDL-C was measured by colorimetric test of venous serum samples. Sarcopenia was defined as low muscle mass, plus low muscle strength, or low physical performance. Muscle mass was estimated by anthropometric measures. Muscle strength was measured by handgrip strength using dynamometer. Physical performance was measured by 5-time chair stand test, gait speed test, and short physical performance battery. RESULTS: With 961 (13.0%) sarcopenia cases, each 1-unit increase (1 SD = 15.4 mg/dL) of HDL-C levels was associated with 42% increased odds of incident sarcopenia (OR = 1.42, 95% confidence interval [CI] = 1.28-1.58) at 4-year follow-up. Females with high HDL-C levels (HDL-C >60 mg/dL) had a higher risk of sarcopenia (OR = 2.49, 95% CI = 1.76-3.52). The restricted cubic spline curves showed a J-shaped association between HDL-C and risk of sarcopenia in females. HDL-C was negatively associated with muscle mass (ß = -0.23, 95% CI = -0.27 to -0.20) and hand grip strength (ß = -0.05, 95% CI = -0.19 to 0.09). CONCLUSION: High HDL-C levels were associated with higher risk of sarcopenia among middle-aged and older Chinese adults, and appropriate control of its high levels informs the management of sarcopenia.


Assuntos
HDL-Colesterol , Vida Independente , Sarcopenia , Humanos , Sarcopenia/sangue , Sarcopenia/epidemiologia , Sarcopenia/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Longitudinais , HDL-Colesterol/sangue , China/epidemiologia , Idoso , Força da Mão/fisiologia , Fatores de Risco , Força Muscular/fisiologia , Desempenho Físico Funcional , População do Leste Asiático
8.
J Assist Reprod Genet ; 41(8): 2145-2161, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38902567

RESUMO

PURPOSE: The objective of this study was to discern ferroptosis-related genes (FRGs) linked to non-obstructive azoospermia and investigate the associated molecular mechanisms. METHOD: A dataset related to azoospermia was retrieved from the Gene Expression Omnibus database, and FRGs were sourced from GeneCards. Ferroptosis-related differentially expressed genes (FRDEGs) were discerned. Subsequently, these genes underwent analyses encompassing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, as well as protein-protein interaction (PPI) networks and assessments of functional similarity. Following the identification of hub genes, an exploration of immune infiltration, single-cell expression, diagnostic utility, and interactions involving hub genes, RNA-binding proteins (RBPs), transcription factors (TFs), microRNAs (miRNAs), and drugs was conducted. RESULTS: A total of 35 differentially expressed FRGs were discerned. These genes demonstrated enrichment in functions and pathways associated with ferroptosis. From the PPI network, eight hub genes were selected. Functional similarity analysis highlighted the potential pivotal roles of HMOX1 and GPX4 in azoospermia. Analysis of immune cell infiltration indicated a significant decrease in activated dendritic cells in the azoospermia group, with notable correlations between hub genes, particularly SAT1 and HMGCR, and immune cell infiltration. Unique expression patterns of hub genes across various cell types in the human testis were observed, with GPX4 prominently enriched in spermatid/sperm. Eight hub genes exhibited robust diagnostic value (AUC > 0.75). Lastly, a comprehensive hub gene-miRNA-TF-RBP-drug network was constructed. CONCLUSION: In summary, our investigation unveiled eight FRDEGs associated with azoospermia, which hold potential as biomarkers for the diagnosis and treatment of azoospermia.


Assuntos
Azoospermia , Biologia Computacional , Ferroptose , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Humanos , Azoospermia/genética , Azoospermia/patologia , Masculino , Ferroptose/genética , Biologia Computacional/métodos , Mapas de Interação de Proteínas/genética , Redes Reguladoras de Genes/genética , MicroRNAs/genética , Perfilação da Expressão Gênica , Ontologia Genética , Fatores de Transcrição/genética , Regulação da Expressão Gênica/genética
9.
Int J Health Plann Manage ; 39(5): 1411-1433, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38804897

RESUMO

BACKGROUND: In the digital era, digital literacy is a fundamental indicator of a nation's quality and plays a crucial role in public health. Exploring the theoretical mechanisms and effects of digital literacy on individuals' health is of great practical importance, advancing the initiatives of 'Digital China' and 'Healthy China'. METHODS: The study utilised three-period survey panel data from the China Family Panel Study spanning 2016, 2018, and 2020 to measure and evaluate levels of digital literacy, physical health, mental health, healthy lifestyle, and integrated health among the participants. Subsequently, a series of empirical analyses were conducted to examine the general impact, heterogeneous effects and transmission pathways of digital literacy on various types of health levels. RESULTS: Digital literacy significantly enhances all aspects of respondents' health, and this conclusion remains valid even after conducting robustness tests and addressing endogeneity through variable substitution and selecting instrumental variables using the 2SLS method. Furthermore, examining heterogeneity by considering individual traits and the makeup of digital literacy reveals that the impact of digital literacy on individuals' health varies according to age, cultural background, personal income, and the components of digital literacy. Pathway analyses also demonstrate that medical accessibility, information access, social network, and planned behaviour are key routes through which digital literacy enhances the health of the population. CONCLUSIONS: It is imperative for the government to actively promote the advancement of the digital healthcare industry, while individuals should strive to enhance their digital literacy. By collectively focussing on these efforts, national health can be significantly improved.


Assuntos
Nível de Saúde , Humanos , China , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Inquéritos e Questionários , Alfabetização Digital , Letramento em Saúde , Saúde Mental , Idoso
10.
Int J Mol Sci ; 25(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38256232

RESUMO

With the explosion research on the gut microbiome in the recent years, much insight has been accumulated in comprehending the crosstalk between the gut microbiota community and host health. Acute pancreatitis (AP) is one of the gastrointestinal diseases associated with significant morbidity and subsequent mortality. Studies have elucidated that gut microbiota are engaged in the pathological process of AP. Herein, we summarize the major roles of the gut microbiome in the development of AP. We then portray the association between dysbiosis of the gut microbiota and the severity of AP. Finally, we illustrate the promises and challenges that arise when seeking to incorporate the microbiome in acute pancreatitis treatment.


Assuntos
Microbioma Gastrointestinal , Microbiota , Pancreatite , Humanos , Doença Aguda , Reações Cruzadas
11.
Int J Mol Sci ; 25(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891899

RESUMO

In aquaculture, viral diseases pose a significant threat and can lead to substantial economic losses. The primary defense against viral invasion is the innate immune system, with interferons (IFNs) playing a crucial role in mediating the immune response. With advancements in molecular biology, the role of non-coding RNA (ncRNA), particularly microRNAs (miRNAs), in gene expression has gained increasing attention. While the function of miRNAs in regulating the host immune response has been extensively studied, research on their immunomodulatory effects in teleost fish, including silver carp (Hyphthalmichthys molitrix), is limited. Therefore, this research aimed to investigate the immunomodulatory role of microRNA-30b-5p (miR-30b-5p) in the antiviral immune response of silver carp (Hypophthalmichthys molitrix) by targeting cytokine receptor family B5 (CRFB5) via the JAK/STAT signaling pathway. In this study, silver carp were stimulated with polyinosinic-polycytidylic acid (poly (I:C)), resulting in the identification of an up-regulated miRNA (miR-30b-5p). Through a dual luciferase assay, it was demonstrated that CRFB5, a receptor shared by fish type I interferon, is a novel target of miR-30b-5p. Furthermore, it was found that miR-30b-5p can suppress post-transcriptional CRFB5 expression. Importantly, this study revealed for the first time that miR-30b-5p negatively regulates the JAK/STAT signaling pathway, thereby mediating the antiviral immune response in silver carp by targeting CRFB5 and maintaining immune system stability. These findings not only contribute to the understanding of how miRNAs act as negative feedback regulators in teleost fish antiviral immunity but also suggest their potential therapeutic measures to prevent an excessive immune response.


Assuntos
Carpas , Proteínas de Peixes , MicroRNAs , Poli I-C , Transdução de Sinais , Animais , Carpas/genética , Carpas/imunologia , Carpas/virologia , Carpas/metabolismo , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Doenças dos Peixes/genética , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata/genética , Janus Quinases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Poli I-C/farmacologia , Fatores de Transcrição STAT/metabolismo , Fatores de Transcrição STAT/genética
12.
J Sci Food Agric ; 104(9): 5139-5148, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38284624

RESUMO

BACKGROUND: The inherent properties of coconut oil (CO), including its elevated saturated fatty acid content and low melting point, make it suitable for application in plastic fat processing. The present study explores the physicochemical characteristics, micromorphology and oxidative stability of oleogels produced from CO using various gelators [ethylcellulose (EC), ß-sitosterol/γ-oryzanol (PS) and glyceryl monostearate (MG)] to elucidate the formation mechanisms of coconut oleogels (EC-COO, PS-COO and MG-COO). RESULTS: Three oleogel systems exhibited a solid-like behavior, with the formation of crystalline forms dominated by ß and ß'. Among them, PS-COO exhibited enhanced capability with respect to immobilizing liquid oils, resulting in solidification with high oil-binding capacity, moderate hardness and good elasticity. By contrast, MG-COO demonstrated inferior stability compared to PS-COO and EC-COO. Furthermore, MG-COO and PS-COO demonstrated antioxidant properties against CO oxidation, whereas EC-COO exhibited the opposite effect. PS-COO and EC-COO exhibited superior thermodynamic behavior compared to MG-COO. CONCLUSION: Three oleogels based on CO were successfully prepared. The mechanical strength, storage modulus and thermodynamic stability of the CO oleogel exhibited concentration dependence with increasing gelling agent addition. PS-COO demonstrated relatively robust oil-binding capacity and oxidative stability, particularly with a 15% PS addition. This information contributes to a deeper understanding of CO-based oleogels and offers theoretical insights for their application in food products. © 2024 Society of Chemical Industry.


Assuntos
Óleo de Coco , Cocos , Compostos Orgânicos , Compostos Orgânicos/química , Óleo de Coco/química , Cocos/química , Oxirredução , Glicerídeos/química , Géis/química , Sitosteroides/química , Antioxidantes/química , Celulose/química , Fenilpropionatos
13.
J Perianesth Nurs ; 39(5): 736-740, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38727654

RESUMO

PURPOSE: Anesthesia nurses play an important postsurgical role during the anesthesia recovery period, which is characterized by a high incidence of complications related to anesthesia and surgery. Strengthening staff allocation and skill management in the postanesthesia care unit (PACU) is therefore particularly important in managing length of stay. We aimed to investigate the effect of two schedule modes for anesthesia nurses on PACU efficiency. DESIGN: A retrospective observational cohort study. METHODS: We conducted a retrospective study in a large tertiary academic medical center. In 2018, the PACU operated with traditional scheduling and the nurse-to-patient ratio was 1.2:1. The PACU implemented intensive scheduling and this ratio was adjusted to 1:1 in 2019 by adjusting the anesthesia nurse allocation scheme. We compared the number of admitted patients, length of PACU stay, the incidence of anesthesia-related complications, and nurse satisfaction with the two modes. FINDINGS: The total number of admitted patients was 10,531 in 2018 and 10,914 in 2019. PACU admitted 401 more patients in 2019 than in 2018, even with two fewer nurses per day. Nevertheless, the median length of PACU stay in 2019 was statistically significantly shorter than in 2018 (29 [22-40] vs 28 [21-39], P < .001], while the incidence of anesthesia-related complications including postoperative pain, nausea and vomiting, hypertension, and shivering were comparable in the 2 years (P > .091). The intensive scheduling implemented in 2019 received more satisfaction from nurses than the traditional scheduling applied in 2018 (P < .01). CONCLUSIONS: The scheduling of anesthesia nurses affects PACU efficiency. The intensive scheduling mode implemented in 2019 resulted in a comparable number of admitted patients, a better quality of care, and higher nurse satisfaction than those under the traditional scheduling mode.


Assuntos
Enfermagem em Pós-Anestésico , Humanos , Estudos Retrospectivos , China , Feminino , Enfermagem em Pós-Anestésico/métodos , Masculino , Pessoa de Meia-Idade , Tempo de Internação/estatística & dados numéricos , Adulto , Admissão e Escalonamento de Pessoal/estatística & dados numéricos , Sala de Recuperação , Enfermeiros Anestesistas/estatística & dados numéricos , Estudos de Coortes
14.
Mol Cancer ; 22(1): 21, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721170

RESUMO

BACKGROUND: Excessive extracellular matrix deposition and increased stiffness are typical features of solid tumors such as hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). These conditions create confined spaces for tumor cell migration and metastasis. The regulatory mechanism of confined migration remains unclear. METHODS: LC-MS was applied to determine the differentially expressed proteins between HCC tissues and corresponding adjacent tissue. Collective migration and single cell migration microfluidic devices with 6 µm-high confined channels were designed and fabricated to mimic the in vivo confined space. 3D invasion assay was created by Matrigel and Collagen I mixture treat to adherent cells. 3D spheroid formation under various stiffness environment was developed by different substitution percentage GelMA. Immunoprecipitation was performed to pull down the LH1-binding proteins, which were identified by LC-MS. Immunofluorescent staining, FRET, RT-PCR, Western blotting, FRAP, CCK-8, transwell cell migration, wound healing, orthotopic liver injection mouse model and in vivo imaging were used to evaluate the target expression and cellular phenotype. RESULTS: Lysyl hydroxylase 1 (LH1) promoted the confined migration of cancer cells at both collective and single cell levels. In addition, LH1 enhanced cell invasion in a 3D biomimetic model and spheroid formation in stiffer environments. High LH1 expression correlated with poor prognosis of both HCC and PDAC patients, while it also promoted in vivo metastasis. Mechanistically, LH1 bound and stabilized Septin2 (SEPT2) to enhance actin polymerization, depending on the hydroxylase domain. Finally, the subpopulation with high expression of both LH1 and SEPT2 had the poorest prognosis. CONCLUSIONS: LH1 promotes the confined migration and metastasis of cancer cells by stabilizing SEPT2 and thus facilitating actin polymerization.


Assuntos
Carcinoma Hepatocelular , Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Animais , Camundongos , Actinas , Carcinoma Hepatocelular/genética , Carcinoma Ductal Pancreático/genética , Neoplasias Hepáticas/genética , Neoplasias Pancreáticas/genética , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/genética , Septinas
15.
Small ; 19(16): e2207194, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36634971

RESUMO

Cancer metastasis is the major cause of cancer-related death. Excessive extracellular matrix deposition and increased stiffness are typical features of solid tumors, creating confined spaces for tumor cell migration and metastasis. Confined migration is involved in all metastasis steps. However, confined and unconfined migration inhibitors are different and drugs available to inhibit confined migration are rare. The main challenges are the modeling of confined migration, the suffering of low throughput, and others. Microfluidic device has the advantage to reduce reagent consumption and enhance throughput. Here, a microfluidic chip that can achieve multi-function drug screening against the collective migration of cancer cells under confined environment is designed. This device is applied to screen out effective drugs on confined migration among a novel mechanoreceptors compound library (166 compounds) in hepatocellular carcinoma, non-small lung cancer, breast cancer, and pancreatic ductal adenocarcinoma cells. Three compounds that can significantly inhibit confined migration in pan-cancer: mitochonic acid 5 (MA-5), SB-705498, and diphenyleneiodonium chloride are found. Finally, it is elucidated that these drugs targeted mitochondria, actin polymerization, and cell viability, respectively. In sum, a high-throughput microfluidic platform for screening drugs targeting confined migration is established and three novel inhibitors of confined migration in multiple cancer types are identified.


Assuntos
Neoplasias Pulmonares , Técnicas Analíticas Microfluídicas , Humanos , Avaliação Pré-Clínica de Medicamentos , Movimento Celular , Microfluídica , Dispositivos Lab-On-A-Chip
16.
Chemistry ; 29(11): e202203106, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36396617

RESUMO

In this work, Ti3 Al1-x Six C2 (x=0, 0.2, 0.4, and 0.6) with Al/Si solid solution structure are synthesized, and the effects of Si on their oxidation behaviors at 1000 °C are evaluated. The addition of Si not only contributes to the formation of Ti5 Si3 impurity but also affects the composition of the oxide scale. Particularly, the incorporation of Si in the TiO2 lattice is demonstrated, which alters the formation energy of the (110) plane in TiO2 , thus leading to the preferential growth of Si-doped TiO2 to dendritic congeries. Moreover, the Si addition is believed to affect mass transportation during the oxidation process, which accelerates the formation of a continuous Al2 O3 layer in the oxide scale. With an optimized Si content, the oxidation of Ti3 Al1-x Six C2 is restrained. However, with excess Si content, the continuity of the resulting Al2 O3 layer is destroyed, thus the oxidation rate rises again.

17.
Langmuir ; 39(47): 16954-16964, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37967372

RESUMO

In this research, the degradation of different types of N-containing heterocycle (NHC) contaminants by Cu-OMS-2 via peroxymonosulfate (PMS) activation in an aqueous environment was investigated. First, the effects of different reaction parameters were optimized using benzotriazole (BTR) as the model contaminant, and the optimal reaction conditions were 8 mM PMS, 0.35 g/L Cu-OMS-2, and 30 °C. Nine different types of NHC contaminants were effectively degraded under these reaction conditions, and the degradation efficiencies and the mineralization rates of those NHCs were more than 68 and 46%, respectively. Moreover, the Cu-OMS-2/PMS process presented excellent performance at a wide pH ranging from 3.0 to 11.0 and in the presence of some representative anions (NO3- and SO42-) and dissolved organic matter (fumaric acid). The inhibition sequence of anions on BTR removal during the Cu-OMS-2/PMS process was H2PO4- > HCO3- > Cl- > CO32- > NO3- > SO42-. It was also found that 74.5 and 71.3% BTR degradation rates were achieved in actual water bodies, such as tap water and Yellow River water, respectively. Besides, the Cu-OMS-2 heterogeneous catalyst had excellent stability and reusability, and the degradation rate of BTR was still at 77.0% after 5 cycles. Finally, electron paramagnetic resonance analysis and scavenging tests showed that 1O2 and SO4- • were the primary reactive oxygen species. Accordingly, Cu-OMS-2 nanomaterial was an efficient and sustainable heterogeneous catalyst to activate PMS for the decontamination of BTR in water remediation.

18.
Clin Exp Dermatol ; 48(12): 1317-1327, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37566911

RESUMO

Heterogeneous dermal fibroblasts are the main components that constitute the dermis. Distinct fibroblast subgroups show specific characteristics and functional plasticity that determine dermal structure during skin development and wound healing. Although researchers have described the roles of fibroblast subsets, this is not completely understood. We review recent evidence supporting understanding about the heterogeneity of fibroblasts. We summarize the origins and the identified profiles of fibroblast subpopulations. The characteristics of fibroblast subpopulations in both healthy and diseased states are highlighted, and the potential of subpopulations to be involved in wound healing in different ways was discussed. Additionally, we review the plasticity of subpopulations and the underlying signalling mechanisms. This review may provide greater insights into potential novel therapeutic targets and tissue regeneration strategies for the future.


Assuntos
Derme , Pele , Humanos , Cicatrização , Fibroblastos , Transdução de Sinais
19.
Chem Biodivers ; 20(5): e202300330, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37014256

RESUMO

Four undescribed polyhydroxy cyclohexanes, fissoxhydrylenes A-D (1-4), together with two known biogenetically related polyhydroxy cyclohexanes (5 and 6) were isolated from the stems of Fissistigma tientangense Tsiang et P. T. Li. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR, UV and Optical rotations data. The absolute configuration of 1 was confirmed by X-ray crystallographic. The absolute configurations of 2-4 were confirmed by chemical reaction and optical rotations. Compound 4 represent the first example of a no substituent polyhydroxy cyclohexanes from natural products. All isolated compounds were evaluated for their anti-inflammatory activities against the lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells in vitro. Compounds 3 and 4 showed inhibitory activities with the IC50 values of 16.63±0.06 µM and 14.38±0.08 µM, respectively.


Assuntos
Annonaceae , Camundongos , Animais , Estrutura Molecular , Annonaceae/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Células RAW 264.7 , Espectroscopia de Ressonância Magnética , Óxido Nítrico
20.
Sensors (Basel) ; 23(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36850596

RESUMO

Cross-chain is an emerging blockchain technology which builds the bridge across homogeneous and heterogeneous blockchains. However, due to the differentiation of different blockchains and the lack of access control and identity authentication of cross-chain operation subjects, existing cross-chain technologies are struggling to accomplish the identity transformation of cross-chain subjects between different chains, and also pose great challenges in terms of the traceability and supervision of dangerous transactions. To address the above issues, this paper proposes a scalable cross-chain access control and identity authentication scheme, which can authenticate the legitimacy of blockchains in the cross-chain system and ensure that all cross-chain operations are carried out by verified users. Furthermore, it will record all cross-chain operations with the help of Superchain in order to regulate and trace illegal transactions. Our scheme is scalable and, at the same time, has low invasiveness to blockchains in the cross-chain system. We implement the scheme and accordingly conduct the evaluations, which prove its security, efficiency, and scalability.

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