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1.
Artigo em Inglês | MEDLINE | ID: mdl-38717638

RESUMO

BACKGROUND: Cardiac hypertrophy is the common pathological process of multiple cardiovascular diseases. However, the molecular mechanisms of cardiac hypertrophy are unclear. Long non-coding RNA (lncRNA), a newly discovered type of transcript that has been demonstrated to function as crucial regulators in the development of cardiovascular diseases. This study revealed a novel regulatory pathway of lncRNA in cardiac hypertrophy. METHODS: The cardiac hypertrophy models were established by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) in HL-1 cardiomyocytes. Adeno-associated virus 9 (AAV9) in vivo and lncRNA Gm15834 and shRNA plasmids in vitro were used to overexpress and knock down lncRNA Gm15834. The myocardial tissue structure, cardiomyocyte area, cardiac function, protein expressions, and binding of lncRNA Gm15834 and Src-associated substrate during mitosis of 68 KDa (Sam68) were detected by hematoxylin and eosin (HE) staining, immunofluorescence staining, echocardiography, western blot and RNA immunoprecipitation (RIP), respectively. RESULTS: In cardiac hypertrophy models, inhibiting lncRNA Gm15834 could decrease Sam68 expression and nuclear factor kappa-B (NF-κB) mediated inflammatory activities in vivo and in vitro, but overexpressing lncRNA Gm15834 showed the opposite results. RIP experiments validated the binding activities between lncRNA Gm15834 and Sam68. Overexpression of Sam68 could counteract the anti-hypertrophy effects of lncRNA Gm15834 knockdown. Meanwhile, in vivo inhibition of lncRNA Gm15834 could inhibit Sam68 expression, reduce NF-κB mediated inflammatory activity and attenuate cardiac hypertrophy. CONCLUSION: Our study revealed a novel regulatory axis of cardiac hypertrophy, which comprised lncRNA Gm15834/Sam68/NF-κB/inflammation, shedding a new light for identifying therapy target of cardiac hypertrophy in clinic.

2.
Child Abuse Negl ; 153: 106812, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38696954

RESUMO

BACKGROUND: Poly-victimization is more detrimental to adolescents' physical and mental health than is a single type of victimization. However, there has been limited research on the trajectory of poly-victimization among Chinese adolescents. OBJECTIVE: Identify the different developmental trajectories of poly-victimization among Chinese adolescents over time and examine the influencing factors of poly-victimization trajectories. METHODS: Data from four surveys conducted between 2020 and 2022, encompassing a cohort of 319 adolescents who had experienced poly-victimization, were utilized to identify their developmental trajectories via group-based trajectory modeling. Potential influencing factors were screened and compared using ANOVA or chi-square tests, while factors affecting the developmental trajectories of poly-victimization were analyzed through multinomial logistic regression. RESULTS: We identified three poly-victimization trajectories among adolescents: increasing poly-victimization (n = 39, 12.2 %), relieved poly-victimization (n = 228, 71.5 %), and fluctuating poly-victimization (n = 52, 16.3 %). Our findings indicate that boys, and those with poor class grade ranking, a lower level of parental education, lower household economy, smoking, drinking, suicide attempts, and suicide ideation, constitute the primary focus for the prevention and treatment of poly-victimization. CONCLUSION: We identified three poly-victimization trajectories, highlighting a significant heterogeneity in poly-victimization development. Understanding the characteristics of these developmental trajectories is crucial for realizing the dynamics of different poly-victimization subgroups and informing effective interventions.

3.
Brain Res Bull ; 211: 110939, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38574865

RESUMO

PURPOSE: To evaluate the potential efficacy of Triptolide (TP) on cerebral ischemia/reperfusion injury (CIRI) and to uncover the underlying mechanism through which TP regulates CIRI. METHODS: We constructed a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to simulate CIRI, and established a lipopolysaccharide (LPS)-stimulated BV-2 cell model to mimic the inflammatory state during CIRI. The neurological deficits score (NS) of mice were measured for assessment of neurologic functions. Both the severity of cerebral infarction and the apoptosis level in mouse brain tissues or cells were respectively evaluated using corresponding techniques. The expression levels of Ionized calcium binding adapter molecule 1 (IBA-1), Inductible Nitric Oxide Synthase (iNOS), Arginase 1 (Arg-1), Tumor necrosis factor-α (TNF-α), Interleukin 1ß (IL-1ß), Cysteine histoproteinase S (CTSS), Fractalkine, chemokine C-X3-C motif receptor 1 (CX3CR1), BCL-2-associated X protein (BAX), and antiapoptotic proteins (Bcl-2) were detected using immunofluorescence, qRT-PCR as well as Western blot, respectively. RESULTS: Relative to the Sham group, treatment with TP attenuated the increased NS, infarct area and apoptosis levels observed in MCAO/R mice. Upregulated expression levels of IBA-1, iNOS, Arg-1, TNF-α and IL-1ß were found in MCAO/R mice, while TP suppressed iNOS, TNF-α and IL-1ß expression, and enhanced Arg-1 expression in both MCAO/R mice and LPS-stimulated BV-2 cells. Besides, TP inhibited the CTSS/Fractalkine/CX3CR1 pathway activation in both MCAO/R mice and LPS-induced BV-2 cells, while overexpression of CTSS reversed such effect. Co-culturing HT-22 cells with TP+LPS-treated BV-2 cells led to enhanced cell viability and decreased apoptosis levels. However, overexpression of CTSS further aggravated HT-22 cell injury. CONCLUSION: TP inhibits not only microglia polarization towards the M1 phenotype by suppressing the CTSS/Fractalkine/CX3CR1 pathway activation, but also HT-22 apoptosis by crosstalk with BV-2 cells, thereby ameliorating CIRI. These findings reveal a novel mechanism of TP in improving CIRI, and offer potential implications for addressing the preventive and therapeutic strategies of CIRI.


Assuntos
Receptor 1 de Quimiocina CX3C , Quimiocina CX3CL1 , Diterpenos , Compostos de Epóxi , Infarto da Artéria Cerebral Média , Fenantrenos , Traumatismo por Reperfusão , Transdução de Sinais , Animais , Diterpenos/farmacologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Fenantrenos/farmacologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , Compostos de Epóxi/farmacologia , Masculino , Quimiocina CX3CL1/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Receptor 1 de Quimiocina CX3C/metabolismo , Camundongos Endogâmicos C57BL , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Apoptose/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Modelos Animais de Doenças
4.
Zoolog Sci ; 41(2): 210-215, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38587916

RESUMO

Protocobitis species are typical cave-dwelling fish, exhibiting distinctive morphological adaptations such as colorless body, lack of eyes, and reduced scales and ribs in response to their extreme cave habitats. Distinct from the recorded species, P. anteroventris, P. polylepis, and P. typhlops, a new species, Protocobitis longicostatus sp. nov., is described from Guangxi Zhuang Autonomous Region, China. Protocobitis longicostatus sp. nov. can easily be distinguished from all known congeners by the following characteristics: whole body covered by scales except head, 12 branched caudal fin rays, and long ribs. These species face threats from habitat degradation, hydrological changes, and environmental pollution. Thus, the conservation of cavefish in China has become an urgent issue.


Assuntos
Cipriniformes , Animais , Cipriniformes/anatomia & histologia , China , Cavernas , Olho , Ecossistema
5.
Clin Exp Hypertens ; 46(1): 2326021, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38525833

RESUMO

PURPOSE: This study aimed to examine the impact of CA on DN and elucidate its underlying molecular mechanisms of inflammation. METHODS: We fed C57BL/6 mice injected with streptozotocin to induce diabetes. In addition, we stimulated NRK-52E cells with 20 mmol/L d-glucose to mimic the diabetic condition. RESULTS: Our findings demonstrated that CA effectively reduced blood glucose levels, and improved DN in mice models. Additionally, CA reduced kidney injury and inflammation in both mice models and in vitro models. CA decreased high glucose-induced ferroptosis of NRK-52E cells by inducing GSH/GPX4 axis. Conversely, the ferroptosis activator or the PI3K inhibitor reversed positive effects of CA on DN in both mice and in vitro models. CA suppressed PAQR3 expression in DN models to promote PI3K/AKT activity. The PAQR3 activator reduced the positive effects of CA on DN in vitro models. Moreover, CA directly targeted the PAQR3 protein to enhance the ubiquitination of the PAQR3 protein. CONCLUSION: Overall, our study has uncovered that CA promotes the ubiquitination of PAQR3, leading to the attenuation of ferroptosis in DN. This effect is achieved through the activation of the PI3K/AKT signaling pathways by disrupting the interaction between PAQR3 and the P110α pathway. These findings highlight the potential of CA as a viable therapeutic option for the prevention of DN and other forms of diabetes.


Assuntos
Ácidos Cafeicos , Diabetes Mellitus , Nefropatias Diabéticas , Ferroptose , Succinatos , Animais , Camundongos , Nefropatias Diabéticas/tratamento farmacológico , Inflamação , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ubiquitinação
6.
J Infect Dis ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427829

RESUMO

BACKGROUND: The immunopathological mechanisms underlying neurosyphilis remain incompletely elucidated, and the diagnosis of neurosyphilis presents challenges. METHODS: We used an antibody microarray to detect 640 proteins in cerebrospinal fluid (CSF) samples collected from 6 non-neurosyphilis and 10 neurosyphilis patients. The levels of CSF CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 in 46 non-neurosyphilis, 51 untreated neurosyphilis, and 31 post-treatment neurosyphilis patients were quantified using enzyme-linked immunosorbent assay. The associations between the levels of these proteins and clinical parameters in neurosyphilis were evaluated using Spearman's analysis, and the diagnostic performance of these proteins in neurosyphilis was assessed using receiver operating characteristic curve. RESULTS: A total of 102 differentially expressed proteins between neurosyphilis and non-neurosyphilis were identified. The levels of significantly elevated neutrophil-associated proteins (CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9) in neurosyphilis were positive correlations with WBC counts, RPR titer, and protein concentration in CSF. The combination of CSF CXCL8, MMP9, and LCN2 yielded an AUC of 0.92 for diagnosing neurosyphilis, surpassing that of CSF RPR. CONCLUSIONS: CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 could be associated with central nervous system damage of neurosyphilis. The combination of CSF CXCL8, MMP9, and LCN2 is a promising biomarker for diagnosing neurosyphilis.

7.
J Nat Prod ; 87(4): 753-763, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38372239

RESUMO

In this study, we isolated lovastatin derivatives, including aculeatiols A-G (1-7) and three known compounds (8-10), from Aspergillus aculeatus. Their structures and absolute configurations were experimentally determined by high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, and X-ray diffraction analyses, and the results were corroborated by quantum-chemical calculations. As members of the lovastatin derivatives, aculeatiols A-C (1-3) possess a γ-lactone functional group in the side chain. Compound 6 represents the first example that features an undescribed aromatized heterotetracyclic 6/6/6/6 ring system. Biologically, the lipid-lowering effects of all of these compounds were evaluated by analyzing the free fatty acid-induced intracellular lipid accumulation. In addition, compound 5, which regulated the transcription of genes associated with lipid uptake and synthesis, inhibited the accumulation of lipids.


Assuntos
Aspergillus , Lovastatina , Aspergillus/química , Lovastatina/farmacologia , Lovastatina/química , Estrutura Molecular , Humanos
8.
Clin Pharmacol Drug Dev ; 13(1): 96-102, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37814913

RESUMO

This study was designed to compare the beneficial effects of paricalcitol combined with or without cinacalcet on calcium and phosphorus metabolism in patients undergoing maintenance hemodialysis (MHD). A total of 140 patients who received MHD in our hospital from March 2021 to March 2022 were randomly divided into a control group (intravenous paricalcitol, n = 70) and a test group (intravenous paricalcitol combined with oral cinacalcet, n = 70). Clinical baseline data and relevant laboratory parameters before treatment were compared. Additionally, calcium, phosphorus, intact parathyroid hormone in serum were measured and compared between the 2 groups before treatment and 1, 2, 3, 4, 5, 6, 9, 10, and 12 months after treatment. As a result, comparison before treatment demonstrated no significant difference in baseline data such as age, sex, and most laboratory parameters between the 2 groups (P > .05), but there was a significant difference in mean corpuscular volume (P < .001). The serum phosphorus level decreased and calcium level increased significantly in the 2 groups after treatment, while the intact parathyroid hormone level showed no significant change within 12 months of treatment (P > .05). In addition, the combined treatment for 6-12 months caused a much lower phosphorus level (P < .05) and higher calcium level (P < .05) than the treatment with paricalcitol alone, and the difference increased with the extension of treatment time. Collectively, paricalcitol combined with cinacalcet, which is more effective than paricalcitol alone, has a positive effect on calcium and phosphorus metabolism in patients receiving MHD.


Assuntos
Cálcio , Hiperparatireoidismo Secundário , Humanos , Cinacalcete/uso terapêutico , Cálcio/uso terapêutico , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/etiologia , Diálise Renal , Hormônio Paratireóideo/uso terapêutico , Fósforo
9.
Heart Fail Rev ; 29(1): 113-123, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37823952

RESUMO

The progression of heart failure is reported to be strongly associated with homeostatic imbalance, such as mitochondrial dysfunction and abnormal autophagy, in the cardiomyocytes. Mitochondrial dysfunction triggers autophagic and cardiac dysfunction. In turn, abnormal autophagy impairs mitochondrial function and leads to apoptosis or autophagic cell death under certain circumstances. These events often occur concomitantly, forming a vicious cycle that exacerbates heart failure. However, the role of the crosstalk between mitochondrial dysfunction and abnormal autophagy in the development of heart failure remains obscure and the underlying mechanisms are mainly elusive. The potential role of the link between mitochondrial dysfunction and abnormal autophagy in heart failure progression has recently garnered attention. This review summarized recent advances of the interactions between mitochondria and autophagy during the development of heart failure.


Assuntos
Insuficiência Cardíaca , Doenças Mitocondriais , Humanos , Insuficiência Cardíaca/metabolismo , Autofagia/fisiologia , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Doenças Mitocondriais/metabolismo
10.
Clin Genitourin Cancer ; 22(2): 134-148.e8, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37919101

RESUMO

BACKGROUND: Kidney cancer is a significant health concern with growing treatment resistance, often linked to genomic instability. This study used datasets from 72 renal and 952 clear cell renal cell carcinoma samples to identify genomic instability-derived lncRNAs and develop a prognostic index (GILPI). METHODS: The study involved differential expression analysis, weighted gene co-expression network analysis, Cox analyses to construct GILPI, and its validation through survival analysis. SNP, TMB, and MSI data were integrated, and GSEA analysis explored associated pathways. A predictive nomogram was created, and immune cell infiltration was assessed. Targeted treatments for low-GILPI patients were identified through molecular docking and network pharmacology. RESULTS: GILPI proved reliable in predicting prognosis (P<0.001, AUC=0.68) and in combination with other factors. GSEA revealed distinct pathway enrichments for different GILPI subgroups. The nomogram exhibited strong predictive performance (AUC=0.902). Immune cell differences suggest potential for immunotherapy in high-GILPI patients and targeted treatment in low-GILPI patients. Lapatinib and nilotinib were identified as effective drugs for low-GILPI patients. CONCLUSION: This study identified a GILPI for kidney cancer prognosis, integrating various factors for a comprehensive assessment. It highlighted potential treatment strategies based on GILPI subgroups, enhancing personalized treatment approaches.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Simulação de Acoplamento Molecular , Prognóstico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Instabilidade Genômica
11.
Zookeys ; 1185: 143-161, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074901

RESUMO

The hedgehog genus Mesechinus (Erinaceidae, Eulipotyphla) is currently comprised of four species, M.dauuricus, M.hughi, M.miodon, and M.wangi. Except for M.wangi, which is found in southwestern China, the other three species are mainly distributed in northern China and adjacent Mongolia and Russia. From 2018 to 2023, we collected seven Mesechinus specimens from Anhui and Zhejiang provinces, eastern China. Here, we evaluate the taxonomic and phylogenetic status of these specimens by integrating molecular, morphometric, and karyotypic approaches. Our results indicate that the Anhui and Zhejiang specimens are distinct from the four previously recognized species and are a new species. We formally described it here as Mesechinusorientalissp. nov. It is the only Mesechinus species occurring in eastern China and is geographically distant from all known congeners. Morphologically, the new species is most similar to M.hughi, but it is distinguishable from that species by the combination of its smaller size, shorter spines, and several cranial characteristics. Mesechinusorientalis sp. nov. is a sister to the lineage composed of M.hughi and M.wangi from which it diverged approximately 1.10 Ma.

12.
Zookeys ; 1185: 21-42, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074905

RESUMO

This work describes a new species, Balitoraanlongensissp. nov., collected from a cave at Xinglong Town, Anlong County, Guzihou, China. Phylogenetic trees reconstructed based on two mitochondrial and three nuclear genes show that the new species represents an independent evolutionary lineage with large genetic differences, 7.1%-12.0% in mitochondrial gene cytochrome b and 9.2%-12.1% in cytochrome oxidase subunit 1, from congeners. Morphologically, the new species can be distinguished from the 18 species currently assigned to the genus Balitora by a combination of characters, most clearly by having two pairs of maxillary barbels; 8½ branched dorsal-fin rays; 5½ branched anal-fin rays; pectoral fin not reaching pelvic fin origin; dorsal-fin origin in front of pelvic fin origin; eye small (eye diameter approximately equal to outer maxillary barbel length); and fins lacking pigment in live fish. The new species represents the first record of Balitora inhabiting caves in China and increases the number of species in the genus Balitora in its present concept from 18 to 19. The study suggests that more evidence is needed to further clarify the taxonomic composition of the genus Balitora.

13.
Zookeys ; 1185: 43-81, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074912

RESUMO

Recently described cave species of the genus Triplophysa have been discovered in southwestern China, suggesting that the diversity of the genus is severely underestimated and that there may be many undescribed species. In this work, four new species of the genus Triplophysa are described from southwestern Guizhou Province, China, namely Triplophysacehengensis Luo, Mao, Zhao, Xiao & Zhou, sp. nov. and Triplophysarongduensis Mao, Zhao, Yu, Xiao & Zhou, sp. nov. from Rongdu Town, Ceheng County, Guizhou, Triplophysapanzhouensis Yu, Luo, Lan, Xiao & Zhou, sp. nov. from Hongguo Town, Panzhou City, Guizhou, and Triplophysaanlongensis Song, Luo, Lan, Zhao, Xiao & Zhou, sp. nov. from Xinglong Town, Anlong County, Guizhou. These four new species can be distinguished from all recognized congeners by a combination of morphological characteristics and significant genetic divergences. The discovery of these species increases the number of known cave species within the genus Triplophysa to 39, making the genus the second most diverse group of cave fishes in China after the golden-line fish genus Sinocyclocheilus. Based on the non-monophyletic relationships of the different watershed systems in the phylogenetic tree, this study also discusses the use of cave species of the genus Triplophysa to determine the possible historical connectivity of river systems.

14.
Digit Discov ; 2(6): 1925-1936, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38054102

RESUMO

Porous organic cages (POCs) are a class of porous molecular materials characterised by their tunable, intrinsic porosity; this functional property makes them candidates for applications including guest storage and separation. Typically formed via dynamic covalent chemistry reactions from multifunctionalised molecular precursors, there is an enormous potential chemical space for POCs due to the fact they can be formed by combining two relatively small organic molecules, which themselves have an enormous chemical space. However, identifying suitable molecular precursors for POC formation is challenging, as POCs often lack shape persistence (the cage collapses upon solvent removal with loss of its cavity), thus losing a key functional property (porosity). Generative machine learning models have potential for targeted computational design of large functional molecular systems such as POCs. Here, we present a deep-learning-enabled generative model, Cage-VAE, for the targeted generation of shape-persistent POCs. We demonstrate the capacity of Cage-VAE to propose novel, shape-persistent POCs, via integration with multiple efficient sampling methods, including Bayesian optimisation and spherical linear interpolation.

15.
Neurosurg Rev ; 47(1): 17, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38112846

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive type of extranodal non-Hodgkin lymphoma (NHL), and the prognosis is poor. Currently, the most used prognostic models are the Memorial Sloan-Kettering Cancer Center (MSKCC) and International Extranodal Lymphoma Study Group (IELSG) scores; however, their predictive effects are changing with increasing incidence and changing treatment regimens. A growing body of evidence has demonstrated that inflammatory and nutritional markers are factors that can determine tumor prognosis. Therefore, the aim of this study was to identify and validate novel prognostic factors for PCNSL. Clinical information was collected from 223 patients with PCNSL. Patients younger than 18 years of age were excluded. Progression-free survival (PFS) and overall survival (OS) were used as endpoints, and receiver operating characteristic (ROC) curve analyses were conducted to determine the cutoff values for the inflammatory indicators. Correlations between variables and PFS or OS were assessed using univariate and multivariate analyses, and positive indicators were selected for survival analysis. A prognostic nutritional index (PNI) < 49.38 was associated with worse PFS (p = 0.003), and outcomes significantly differed between patients with a PNI ≥ 49.38 and < 49.38 (p < 0.001). Age < 60 years (p < 0.001) and C-reactive protein (CRP) levels < 3.14 (p = 0.001) were associated with better OS. In elderly patients (≥ 60 years), a lactate dehydrogenase-to-lymphocyte ratio (LLR) < 95.69 (p = 0.021) was associated with better OS, and the outcome significantly differed between patients with an LLR ≥ 95.69 and LLR < 95.69 (p = 0.015). The PNI and CRP levels are prognostic factors for PCNSL, and CRP was the first time shown to be a prognosis factor of PCNSL. In elderly patients with PCNSL, the LLR can predict prognosis.


Assuntos
Linfoma , Avaliação Nutricional , Humanos , Idoso , Pessoa de Meia-Idade , Prognóstico , Proteína C-Reativa , Linfócitos , Linfoma/diagnóstico , Sistema Nervoso Central , Lactato Desidrogenases , Estudos Retrospectivos
16.
Cell Death Discov ; 9(1): 466, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114486

RESUMO

Research suggests that ischemic glycolysis improves myocardial tolerance to anoxia and low-flow ischemia. The rate of glycolysis during ischemia reflects the severity of the injury caused by ischemia and subsequent functional recovery following reperfusion. Histone H2AK119 ubiquitination (H2Aub) is a common modification that is primarily associated with gene silencing. Recent studies have demonstrated that H2Aub contributes to the development of cardiovascular diseases. However, the underlying mechanism remains unclear. This study identified Hsp27 (heat shock protein 27) as a H2Aub binding protein and explored its involvement in mediating glycolysis and mitochondrial function. Functional studies revealed that inhibition of PRC1 (polycomb repressive complex 1) decreased H2Aub occupancy and promoted Hsp27 expression through inhibiting ubiquitination. Additionally, it increased glycolysis by activating the NF-κB/PFKFB3 signaling pathway during myocardial ischemia. Furthermore, Hsp27 reduced mitochondrial ROS production by chaperoning COQ9, and suppressed ferroptosis during reperfusion. A delivery system was developed based on PCL-PEG-MAL (PPM)-PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver PRT4165 (PRT), a potent inhibitor of PRC1, to damaged myocardium, resulting in decreased H2Aub. These findings revealed a novel epigenetic mechanism connecting glycolysis and ferroptosis in protecting the myocardium against ischemia/reperfusion injury.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38015682

RESUMO

Most deep neural networks (DNNs) consist fundamentally of convolutional and/or fully connected layers, wherein the linear transform can be cast as the product between a filter matrix and a data matrix obtained by arranging feature tensors into columns. Recently proposed deformable butterfly (DeBut) decomposes the filter matrix into generalized, butterfly-like factors, thus achieving network compression orthogonal to the traditional ways of pruning or low-rank decomposition. This work reveals an intimate link between DeBut and a systematic hierarchy of depthwise and pointwise convolutions, which explains the empirically good performance of DeBut layers. By developing an automated DeBut chain generator, we show for the first time the viability of homogenizing a DNN into all DeBut layers, thus achieving extreme sparsity and compression. Various examples and hardware benchmarks verify the advantages of All-DeBut networks. In particular, we show it is possible to compress a PointNet to 5% parameters with 5% accuracy drop, a record not achievable by other compression schemes.

18.
Biomed Pharmacother ; 168: 115142, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37806087

RESUMO

Regulatory T cells are a subgroup of T cells with immunomodulatory functions. Different from most cytotoxic T cells and helper T cells, they play a supporting role in the immune system. What's more, regulatory T cells often play an immunosuppressive role, which mainly plays a role in maintaining the stability of the immune system and regulating the immune response in the body. However, recent studies have shown that not only playing a role in autoimmune diseases, organ transplantation, and other aspects, regulatory T cells can also play a role in the immune escape of tumors in the body, through various mechanisms to help tumor cells escape from the demic immune system, weakening the anti-cancer effect in the body. For a better understanding of the role that regulatory T cells can play in cancer, and to be able to use regulatory T cells for tumor immunotherapy more quickly. This review focuses on the research progress of various mechanisms of regulatory T cells in the tumor environment, the related research of tumor cells acting on regulatory T cells, and the existing various therapeutic methods acting on regulatory T cells.


Assuntos
Neoplasias , Linfócitos T Reguladores , Humanos , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Linfócitos T Citotóxicos , Imunomodulação , Microambiente Tumoral
19.
Zookeys ; 1182: 207-221, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37881412

RESUMO

Formosaniaimmaculata, a new species, is described from the Ou-Jiang basin in Zhejiang Province, Southeast China. It is distinguished from other species of the genus by having a combination of the following characteristics: body without obvious mottling; snout length longer than postorbital length; abdominal scaleless area extending to middle of pectoral-fin base; shorter rostral barbels, the outermost pair length 112.9%-140.0% of eye diameter; and shorter lower lip papillae, length 19.9%-24.4% of eye diameter. Its validity is also affirmed by its distinct Cytb gene sequence divergence from all congeners and its monophyly recovered in a Cytb gene-based phylogenetic analysis.

20.
Zookeys ; 1180: 81-104, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37767522

RESUMO

In this work, a new species of the genus Oreonectes is described, named Oreonectesdamingshanensis Yu, Luo, Lan, Xiao & Zhou, sp. nov., collected from the Damingshan Mountains of the Guangxi Zhuang Autonomous Region, China. Phylogenetic trees constructed based on the mitochondrial Cyt b showed that the new species represents an independent evolutionary lineage, with uncorrected genetic distances (p-distance) from congeners ranging from 6.1% to 8.9%. Morphologically, the new species can be distinguished from five other species of the genus by a combination of characters. The discovery of this new species raises the number of known species of Oreonectes from five to six. Our study suggests that O.platycephalus may be a complex containing multiple species and that previously recorded areas need to be further delimited and reevaluated.

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