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1.
Neural Regen Res ; 20(1): 277-290, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38767492

RESUMO

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

2.
Cereb Cortex ; 34(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38836287

RESUMO

Somatic mutations have been identified in 10% to 63% of focal cortical dysplasia type II samples, primarily linked to the mTOR pathway. When the causative genetic mutations are not identified, this opens the possibility of discovering new pathogenic genes or pathways that could be contributing to the condition. In our previous study, we identified a novel candidate pathogenic somatic variant of IRS-1 c.1791dupG in the brain tissue of a child with focal cortical dysplasia type II. This study further explored the variant's role in causing type II focal cortical dysplasia through in vitro overexpression in 293T and SH-SY5Y cells and in vivo evaluation via in utero electroporation in fetal brains, assessing effects on neuronal migration, morphology, and network integrity. It was found that the mutant IRS-1 variant led to hyperactivity of p-ERK, increased cell volume, and was predominantly associated with the MAPK signaling pathway. In vivo, the IRS-1 c.1791dupG variant induced abnormal neuron migration, cytomegaly, and network hyperexcitability. Notably, the ERK inhibitor GDC-0994, rather than the mTOR inhibitor rapamycin, effectively rescued the neuronal defects. This study directly highlighted the ERK signaling pathway's role in the pathogenesis of focal cortical dysplasia II and provided a new therapeutic target for cases of focal cortical dysplasia II that are not treatable by rapamycin analogs.


Assuntos
Proteínas Substratos do Receptor de Insulina , Sistema de Sinalização das MAP Quinases , Mutação , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Animais , Malformações do Desenvolvimento Cortical do Grupo I/genética , Malformações do Desenvolvimento Cortical do Grupo I/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Neurônios/metabolismo , Neurônios/patologia , Movimento Celular/genética , Células HEK293 , Feminino , Displasia Cortical Focal , Epilepsia
3.
PhytoKeys ; 242: 161-227, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854497

RESUMO

This study addresses the longstanding absence of a comprehensive phylogenetic backbone for the apple tribe Maleae, a deficiency attributed to limited taxon and marker sampling. We conducted an extensive taxon sampling, incorporating 563 plastomes from a diverse range of 370 species encompassing 26 presently recognized genera. Employing a range of phylogenetic inference methods, including RAxML and IQ-TREE2 for Maximum Likelihood (ML) analyses, we established a robust phylogenetic framework for the Maleae tribe. Our phylogenomic investigations provided compelling support for three major clades within Maleae. By integrating nuclear phylogenetic data with morphological and chromosomal evidence, we propose an updated infra-tribal taxonomic system, comprising subtribe Malinae Reveal, subtribe Lindleyinae Reveal, and subtribe Vauqueliniinae B.B.Liu (subtr. nov.). Plastid phylogenetic analysis also confirmed the monophyly of most genera, except for Amelanchier, Malus, Sorbus sensu lato, and Stranvaesia. In addition, we present a comprehensive taxonomic synopsis of Photinia and its morphological allies in the Old World, recognizing 27 species and ten varieties within Photinia, three species and two varieties within Stranvaesia, and two species and three varieties within Weniomeles. Furthermore, we also lectotypified 12 names and made two new combinations, Photiniamicrophylla (J.E.Vidal) B.B.Liu and Weniomelesatropurpurea (P.L.Chiu ex Z.H.Chen & X.F.Jin) B.B.Liu.

4.
Front Pharmacol ; 15: 1393693, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855753

RESUMO

Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhibitors that block the active causes of MDR may provide a strategy for the treatment of colorectal cancer. In this study, we find that dorsomorphin (also known as compound C or BML-275) potently inhibits the transporter activity of ABCG2, thereby preserving the chemotherapeutic agents mitoxantrone and doxorubicin to antagonize MDR in ABCG2-overexpressing colorectal cancer cells. Additionally, dorsomorphin does not alter ABCG2 protein expression. The results of molecular docking studies show that dorsomorphin is bound stably to the ABCG2-binding pocket, suggesting that dorsomorphin is a potent ABCG2 inhibitor that attenuates ABCG2-mediated MDR in colorectal cancer.

5.
Opt Express ; 32(12): 21293-21303, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859487

RESUMO

Metasurfaces made of subwavelength silicon nanopillars provide unparalleled capacity to manipulate light, and have emerged as one of the leading platforms for developing integrated photonic devices. In this study, we report on a compact, passive approach based on planar metasurface optics to generate large optical trap arrays. The unique configuration is achieved with a meta-hologram to convert a single incident laser beam into an array of individual beams, followed up with a metalens to form multiple laser foci for single rubidium atom trapping. We experimentally demonstrate two-dimensional arrays of 5 × 5 and 25 × 25 at the wavelength of 830 nm, validating the capability and scalability of our metasurface design. Beam waists ∼1.5 µm, spacings (about 15 µm), and low trap depth variations (8%) of relevance to quantum control for an atomic array are achieved in a robust and efficient fashion. The presented work highlights a compact, stable, and scalable trap array platform well-suitable for Rydberg-state mediated quantum gate operations, which will further facilitate advances in neutral atom quantum computing.

6.
Fitoterapia ; 177: 106068, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38857833

RESUMO

Rosin, a natural resin obtained from conifer trees, has a long history of use in traditional folk medicine for treating abscesses, wounds, carbuncles, and burns, etc. It has been employed in ancient Egypt, China, Nordic countries, and Turkey as a therapeutic remedy. This comprehensive review examines the traditional uses, phytochemistry, and pharmacology of rosin, and it provides a critical update on current knowledge of rosin and identifies potential therapeutic opportunities. The chemical composition of rosin is known to vary depending on factors such as botanical sources, geographical locations, and processing methods. Rosin acids, which account for over 90% of its primary chemical constituents, have been identified as the predominant compounds in rosin. Researchers have isolated approximately 50 compounds from rosin, with terpenoid rosin acids being the most prevalent. Furthermore, the review highlights the potential pharmacological activities of rosin and its constituents. Crude extracts and isolated rosin acids have demonstrated promising properties, including antimicrobial, anti-inflammatory, anti-tumor, insecticidal, wound healing, and anti-obesity effects. However, the review emphasizes that further research is needed, as existing studies are predominantly preliminary. Many of the reported bioactivities require further verification, and the underlying mechanisms of action remain largely unexplored. In conclusion, rosin has been extensively used in traditional medicine across different cultures, and its chemical composition has been confirmed to a significant extent. The pharmacological activities observed in crude extracts and isolated rosin acids support its traditional uses. Nevertheless, additional research is necessary to deepen our understanding of the pharmacological mechanisms underlying its effects.

7.
Front Plant Sci ; 15: 1403276, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863531

RESUMO

Flax powdery mildew (PM), caused by Oidium lini, is a globally distributed fungal disease of flax, and seriously impairs its yield and quality. To data, only three resistance genes and a few putative quantitative trait loci (QTL) have been reported for flax PM resistance. To dissect the resistance mechanism against PM and identify resistant genetic regions, based on four years of phenotypic datasets (2017, 2019 to 2021), a genome-wide association study (GWAS) was performed on 200 flax core accessions using 674,074 SNPs and 7 models. A total of 434 unique quantitative trait nucleotides (QTNs) associated with 331 QTL were detected. Sixty-four loci shared in at least two datasets were found to be significant in haplotype analyses, and 20 of these sites were shared by multiple models. Simultaneously, a large-effect locus (qDI 11.2) was detected repeatedly, which was present in the mapping study of flax pasmo resistance loci. Oil flax had more QTL with positive-effect or favorable alleles (PQTL) and showed higher PM resistance than fiber flax, indicating that effects of these QTL were mainly additive. Furthermore, an excellent resistant variety C120 was identified and can be used to promote planting. Based on 331 QTLs identified through GWAS and the statistical model GBLUP, a genomic selection (GS) model related to flax PM resistance was constructed, and the prediction accuracy rate was 0.96. Our results provide valuable insights into the genetic basis of resistance and contribute to the advancement of breeding programs.

8.
Huan Jing Ke Xue ; 45(6): 3142-3152, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38897738

RESUMO

Groundwater contaminants pose a great threat to water safety and human health. Therefore, in this study, the traditional hazard assessment method was improved and a comprehensive system covering hazard assessment, screening, and characterization by combining the toxicological priority index (Tox Pi) framework; absorption, distribution, metabolism, and excretory (ADME) analysis; and bipartite network analysis was constructed. Then, the system was applied to hazard assessment and toxic pollutants screening from the 234 hydrophobic organic contaminants (HOCs) identified in the groundwater of Beijing. First, the top 20 pollutants with hazard potential were screened out using the Tox Pi method. Subsequently, 17 high-priority HOCs were further identified based on the ADME property analysis. Then, the molecular targets of these 17 high-priority HOCs were characterized through systematic bipartite network analysis. Finally, ten HOCs with high hazard were screened through correlation and weighted average analysis, and it was revealed that their toxic effects were mainly concentrated in the endocrine-disrupting effect, carcinogenic effect, and genetic toxicity. This study provides technical support for the prevention of regional groundwater contaminants.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Água Subterrânea/análise , Monitoramento Ambiental/métodos , Pequim , Substâncias Perigosas/análise , Compostos Orgânicos/análise , Medição de Risco
9.
Huan Jing Ke Xue ; 45(6): 3205-3213, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38897744

RESUMO

To improve the accuracy and stability of water quality prediction in the Pearl River Estuary, a water quality prediction model was proposed based on BiLSTM improved with an attention mechanism. The feature attention mechanism was introduced to enhance the ability of the model to capture important features, and the temporal attention mechanism was added to improve the mining ability of time series correlation information and water quality fluctuation details. The new model was applied to the water quality prediction of eight estuaries of the Pearl River, and the prediction performance test, generalization ability test, and characteristic parameter expansion test were carried out. The results showed that:① The new model achieved high prediction accuracy in the water quality prediction of the Zhuhaidaqiao section. The root-mean-square error (RMSE) between the predicted value and the measured value was 0.004 1 mg·L-1, and the coefficient of determination (R2) was 98.3 %. Compared with that of Multi-BiLSTM, Multi-LSTM, BiLSTM, and LSTM, the results showed that the new model had the highest prediction accuracy, which verified the accuracy of the model. ② Both the number of training samples and the number of forecasting steps affected the prediction accuracy of the model, and the prediction accuracy of the model increased with the increase of the training samples. When predicting the total phosphorus of the Zhuhaidaqiao section, more than 240 training samples could obtain higher prediction accuracy. Increasing the number of prediction steps caused the prediction accuracy of the model to decline rapidly, and the reliability of the model prediction could not be guaranteed when the number of prediction steps was greater than 5. ③ When the new model was applied to the prediction of different water quality indexes in eight estuaries of the Pearl River, the prediction results had high precision and the model had strong generalization ability. The input data of upstream water quality, rainfall, and other characteristic parameters associated with the section prediction index of the object could improve the prediction accuracy of the model. Through many tests, the results showed that the new model could meet the requirements of precision, applicability, and expansibility of water quality prediction in the Pearl River Estuary and thus is a new exploration method for high-precision prediction of water quality in complex hydrodynamic environments.

10.
Zhen Ci Yan Jiu ; 49(6): 641-649, 2024 Jun 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38897809

RESUMO

Acupuncture is an effective measure for treating type 2 diabetes mellitus (T2DM). Many studies have shown that acupuncture can reduce blood glucose in patients with T2DM, but its mechanism is still unclear. This review summarized the mechanism of acupuncture on T2DM, the mechanisms of acupuncture in treating T2DM is related to improving insulin resistance, regulating inflammation, promoting insulin secretion, improving lipid metabolism disorders, resisting oxidative stress, improving obesity, controlling intestinal flora, and regulating the nervous system. At the same time, this review also points out the lack of current relevant research and the future research directions to provide a reference for further exploring the mechanism of acupuncture hypoglycemic action.


Assuntos
Terapia por Acupuntura , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/metabolismo , Animais , Resistência à Insulina , Glicemia/metabolismo , Insulina/metabolismo , Estresse Oxidativo
11.
J Asian Nat Prod Res ; : 1-7, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900038

RESUMO

A new cladosporol derivative xylophilum A (1), together with 10 known compounds (2-11), were isolated from the rice fermentation of the fungus Cladosporium xylophilum. Their structures were established by extensive spectroscopic methods and comparison of their NMR data with literatures. The antimicrobial activity of compound 1 against 11 kinds of pathogenic microbial was evaluated, but no significant activity was found (MIC >100 µg/ml).

12.
Chin J Integr Med ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900227

RESUMO

The hippocampus is one of the most commonly studied brain regions in the context of depression. The volume of the hippocampus is significantly reduced in patients with depression, which severely disrupts hippocampal neuroplasticity. However, antidepressant therapies that target hippocampal neuroplasticity have not been identified as yet. Chinese medicine (CM) can slow the progression of depression, potentially by modulating hippocampal neuroplasticity. Xiaoyaosan (XYS) is a CM formula that has been clinically used for the treatment of depression. It is known to protect Gan (Liver) and Pi (Spleen) function, and may exert its antidepressant effects by regulating hippocampal neuroplasticity. In this review, we have summarized the association between depression and aberrant hippocampal neuroplasticity. Furthermore, we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against depression. The results of this review can aid future research on XYS for the treatment of depression.

13.
Chemphyschem ; : e202400414, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896533

RESUMO

We systematically investigated the stable configurations and catalytic activity in the Oxygen Reduction Reaction (ORR) of graphene co-doped with boron and nitrogen (B-N) using first-principles methods. Compared to single B/N doping, co-doping with BN is energetically favored. We found that intermediate species of ORR process adsorb on boron atoms, which act as catalytic sites. The presence of neighboring nitrogen atoms around boron plays a crucial role in modulating the catalytic activity of boron. For the same adsorption configuration, the adsorption energy of the adsorbate increases with the number of neighboring nitrogen atoms around boron and generally correlates positively with the number of electrons gained by the adsorbate. Regarding the catalytic activity of ORR, excessively strong adsorption of adsorbates impedes their hydrogenation. The best substrates for ORR catalytic activity are B-N-graphene and N-B2-graphene, with the rate-determining step being the hydrogenation of *OO and overpotentials of 0.49 V and 0.54 V, respectively.

14.
Anal Biochem ; 692: 115580, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38825159

RESUMO

Ricin is one of the most toxic substances known and a type B biothreat agent. Shiga toxins (Stxs) produced by E. coli (STEC) and Shigella dysenteriae are foodborne pathogens. There is no effective therapy against ricin or STEC and there is an urgent need for inhibitors. Ricin toxin A subunit (RTA) and A1 subunit of Stx2a (Stx2A1) bind to the C-terminal domain (CTD) of the ribosomal P-stalk proteins to depurinate the sarcin/ricin loop. Modulation of toxin-ribosome interactions has not been explored as a strategy for inhibition. Therefore, development of assays that detect inhibitors targeting toxin-ribosome interactions remains a critical need. Here we describe a fluorescence anisotropy (FA)-based competitive binding assay using a BODIPY-TMR labeled 11-mer peptide (P11) derived from the P-stalk CTD to measure the binding affinity of peptides ranging from 3 to 11 amino acids for the P-stalk pocket of RTA and Stx2A1. Comparison of the affinity with the surface plasmon resonance (SPR) assay indicated that although the rank order was the same by both methods, the FA assay could differentiate better between peptides that show nonspecific interactions by SPR. The FA assay detects only interactions that compete with the labeled P11 and can validate inhibitor specificity and mechanism of action.


Assuntos
Polarização de Fluorescência , Ribossomos , Ricina , Ricina/antagonistas & inibidores , Ricina/metabolismo , Ricina/química , Polarização de Fluorescência/métodos , Ribossomos/metabolismo , Ressonância de Plasmônio de Superfície , Toxina Shiga/antagonistas & inibidores , Toxina Shiga/metabolismo , Toxina Shiga/química , Ligação Competitiva , Ligação Proteica , Toxina Shiga II/antagonistas & inibidores , Toxina Shiga II/metabolismo , Toxina Shiga II/química
15.
iScience ; 27(6): 109988, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38883835

RESUMO

The association between visual abnormalities and impairments in cerebral blood flow and brain region potentially results in neural dysfunction of amblyopia. Nevertheless, the differences in the complex mechanisms of brain neural network coupling and its relationship with neurotransmitters remain unclear. Here, the neurovascular coupling mechanism and neurotransmitter activity in children with anisometropic amblyopia (AA) and visual deprivation amblyopia (VDA) was explored. The neurovascular coupling of 17 brain regions in amblyopia children was significantly abnormal than in normal controls. The classification abilities of coupling units in brain regions differed between two types of amblyopia. Correlations between different coupling effects and neurotransmitters were different. The findings of this study demonstrate a correlation between the neurovascular coupling and neurotransmitter in children with AA and VDA, implying their impaired neurovascular coupling function and potential molecular underpinnings. The neuroimaging evidence revealed herein offers potential for the development of neural therapies for amblyopia.

16.
Metabolism ; 157: 155954, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878856

RESUMO

BACKGROUND: Metabolic diseases contribute significantly to premature mortality worldwide, with increasing burdens observed among the working-age population (WAP). This study assessed global, regional, and national trends in metabolic disorders and associated mortality over three decades in WAP. METHODS: Data from the Global Burden of Disease 2019 study were leveraged to assess global metabolism-associated mortality and six key metabolic risk factors in WAP from 1990-2019. An age-period-cohort model was employed to determine the overall percentage change in mortality. RESULTS: The 2019 global metabolic risk-related mortality rate in WAP rose significantly by 50.73%, while the age-standardized mortality rate declined by 21.5%. India, China, Indonesia, the USA, and the Russian Federation were the top contributing countries to mortality in WAP, accounting for 51.01% of the total. High systolic blood pressure (HSBP), high body mass index (HBMI), and high fasting plasma glucose (HFPG) were the top metabolic risk factors for the highest mortality rates. Adverse trends in HBMI-associated mortality were observed, particularly in lower sociodemographic index (SDI) regions. HFPG-related mortality declined globally but increased in older age groups in lower SDI countries. CONCLUSIONS: Despite a general decline in metabolic risk-related deaths in WAP, increasing HBMI- and HFPG-related mortality in lower SDI areas poses ongoing public health challenges. Developing nations should prioritize interventions addressing HBMI and HFPG to mitigate mortality risks in WAP.

17.
Eur J Oncol Nurs ; 71: 102623, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38880040

RESUMO

PURPOSE: This study aimed to investigate the factors associated with perceived cognitive function among breast cancer patients treated with chemotherapy in China. METHODS: The study was a multicenter cross-sectional design. Data were collected from 10 public hospitals in China between April 2022 and February 2023. A total of 741 participants completed questionnaires assessing sociodemographic and medical characteristics, perceived cognitive function, sleep quality, fatigue, anxiety, and depression. Hierarchical multiple regression analysis was used to assess the determinants of cognitive function. RESULTS: The hierarchical multiple regression model accounted for 31.5% of variation in perceived cognitive function (sociodemographic 4.5%; medical 6.6%; exercise frequency 6.6%; sleep quality 2.1%; fatigue 2.8%; anxiety combined with depression 9.0%). Education level, chemotherapy type, number of chemotherapy cycles, and cyclophosphamide drug use were significant predisposing factors of perceived cognitive function (p < 0.001). Exercising ≥3 times/week (p < 0.001) was a significant factor positively influencing perceived cognitive function, meanwhile, anxiety (p < 0.001) and depression (p < 0 0.001) were negative factors. CONCLUSION: Our findings suggest that patients with low education levels, postoperative chemotherapy, cyclophosphamide treatment, and a greater number of chemotherapy cycles need more assessment. Sedentary patients, those who have never exercised, and those with anxiety or depression all showed greater cognitive decline. By identifying susceptible populations, encouraging regular exercise, and addressing anxiety and depression, healthcare professionals can contribute significantly to prevent patients' cognitive decline throughout chemotherapy.

18.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167284, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851304

RESUMO

AIM: Methamphetamine (METH) chronic exposure is an important risk factor for hypertension development. However, the mechanisms behind METH-induced hypertension remain unclear. Therefore, we aimed to reveal the potential mechanisms underlying METH-induced hypertension. METHODS AND RESULTS: We structured the mouse hypertension model by METH, and observed that METH-treated mice have presented vascular remodeling (large-and small-size arteries) with collagen deposit around the vessel and increasing blood pressure (BP) and Sigma1 receptor (Sigmar1) in vascular tissue. We hypothesized that Sigmar1 is crucial in METH-induced hypertension and vascular remodeling. Sigmar1 knockout (KO) mice and antagonist (BD1047) pretreated mice exposed to METH for six-week showed higher BP and more collagen deposited around vessels than wild-type (WT) mice exposed to METH for six-week, in contrast, mice pretreated with Sigmar1 agonist (PRE-084) had unchanged BP and perivascular collagen despite the six-week METH exposure. Furthermore, we found that METH exposure induced vascular smooth muscle cells (VSMCs) and mesenchymal stem cells to differentiate into the myofibroblast-like cell and secrete collagen into surrounding vessels. Mechanically, Sigmar1 can suppress the COL1A1 expression by blocking the classical fibrotic TGF-ß/Smad2/3 signaling pathway in METH-exposed VSMCs and mesenchymal stem cells. CONCLUSION: Our results suggest that Sigmar1 is involved in METH-induced hypertension and vascular fibrosis by blocking the activation of the TGF-ß/Smad2/3 signaling pathway. Accordingly, Sigmar1 may be a novel therapeutic target for METH-induced hypertension and vascular fibrosis.

19.
J Ovarian Res ; 17(1): 124, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851728

RESUMO

Ovarian cancer (OV) is a highly fatal malignant disease that commonly manifests at an advanced stage. Drug resistance, particularly platinum resistance, is a leading cause of treatment failure because first-line systemic chemotherapy primarily relies on platinum-based regimens. By analyzing the gene expression levels in the Cancer Genome Atlas database, Genotype-Tissue Expression database, and Gene Expression Omnibus datasets, we discerned that HOXB2 was highly expressed in OV and was associated with poor prognosis and cisplatin resistance. Immunohistochemistry and loss-of-function experiments on HOXB2 were conducted to explore its role in OV. We observed that suppressing HOXB2 could impair the growth and cisplatin resistance of OV in vivo and in vitro. Mechanical investigation and experimental validation based on RNA-Seq revealed that HOXB2 regulated ATP-binding cassette transporter members and the ERK signaling pathway. We further demonstrated that HOXB2 modulated the expression of long non-coding RNA DANCR, a differentiation antagonizing non-protein coding RNA, and thus influenced its downstream effectors ABCA1, ABCG1, and ERK signaling to boost drug resistance and cancer proliferation. These results verified that high expression of HOXB2 correlated with platinum resistance and poor prognosis of OV. Therefore, targeting HOXB2 may be a promising strategy for OV therapy.


Assuntos
Cisplatino , Resistencia a Medicamentos Antineoplásicos , Proteínas de Homeodomínio , Neoplasias Ovarianas , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Linhagem Celular Tumoral , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação Neoplásica da Expressão Gênica , Animais , Regulação para Cima , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células , Prognóstico , Camundongos
20.
BMC Cancer ; 24(1): 685, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840106

RESUMO

BACKGROUND: Gastric cancer is one of the most common tumors worldwide, and most patients are deprived of treatment options when diagnosed at advanced stages. PRDM14 has carcinogenic potential in breast and non-small cell lung cancer. however, its role in gastric cancer has not been elucidated. METHODS: We aimed to elucidate the expression of PRDM14 using pan-cancer analysis. We monitored the expression of PRDM14 in cells and patients using quantitative polymerase chain reaction, western blotting, and immunohistochemistry. We observed that cell phenotypes and regulatory genes were influenced by PRDM14 by silencing PRDM14. We evaluated and validated the value of the PRDM14-derived prognostic model. Finally, we predicted the relationship between PRDM14 and small-molecule drug responses using the Connectivity Map and The Genomics of Drug Sensitivity in Cancer databases. RESULTS: PRDM14 was significantly overexpressed in gastric cancer, which identified in cell lines and patients' tissues. Silencing the expression of PRDM14 resulted in apoptosis promotion, cell cycle arrest, and inhibition of the growth and migration of GC cells. Functional analysis revealed that PRDM14 acts in epigenetic regulation and modulates multiple DNA methyltransferases or transcription factors. The PRDM14-derived differentially expressed gene prognostic model was validated to reliably predict the patient prognosis. Nomograms (age, sex, and PRDM14-risk score) were used to quantify the probability of survival. PRDM14 was positively correlated with sensitivity to small-molecule drugs such as TPCA-1, PF-56,227, mirin, and linsitinib. CONCLUSIONS: Collectively, our findings suggest that PRDM14 is a positive regulator of gastric cancer progression. Therefore, it may be a potential therapeutic target for gastric cancer.


Assuntos
Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas , Fatores de Transcrição , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Prognóstico , Linhagem Celular Tumoral , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Feminino , Masculino , Nomogramas , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Epigênese Genética
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