Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.004
Filtrar
1.
J Neuroinflammation ; 21(1): 123, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725082

RESUMO

BACKGROUND: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). METHODS: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2-/-) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. RESULTS: The Lrrk2-/--HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2-/- group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2-/--HE mice presented no severer neuronal injury than the other genotypes. CONCLUSIONS: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver.


Assuntos
Encefalopatia Hepática , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Falência Hepática Aguda , Camundongos Knockout , Tioacetamida , Animais , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Tioacetamida/toxicidade , Camundongos , Encefalopatia Hepática/patologia , Encefalopatia Hepática/genética , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Falência Hepática Aguda/genética , Masculino , Camundongos Endogâmicos C57BL
2.
Natl Sci Rev ; 11(6): nwae146, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38741713

RESUMO

Lithiated organic cathode materials show great promise for practical applications in lithium-ion batteries owing to their Li-reservoir characteristics. However, the reported lithiated organic cathode materials still suffer from strict synthesis conditions and low capacity. Here we report a thermal intermolecular rearrangement method without organic solvents to prepare dilithium hydroquinone (Li2Q), which delivers a high capacity of 323 mAh g-1 with an average discharge voltage of 2.8 V. The reversible conversion between orthorhombic Li2Q and monoclinic benzoquinone during charge/discharge processes is revealed by in situ X-ray diffraction. Theoretical calculations show that the unique Li-O channels in Li2Q are beneficial for Li+ ion diffusion. In situ ultraviolet-visible spectra demonstrate that the dissolution issue of Li2Q electrodes during charge/discharge processes can be handled by separator modification, resulting in enhanced cycling stability. This work sheds light on the synthesis and battery application of high-capacity lithiated organic cathode materials.

3.
Oral Dis ; 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735833

RESUMO

BACKGROUND: Diabetes is accompanied by a high prevalence of hyposalivation, causing severe damage to oral and systemic health. Mitochondrial dynamics play important roles in the pathogenesis of various diabetic complications; however, little is known about their roles in diabetic hyposalivation. MATERIALS AND METHODS: A diabetic mouse model and a high glucose (HG)-induced diabetic submandibular gland (SMG) cell model were employed. RESULTS: More mitochondria surrounded by autophagosomes and higher expression of mitophagy-related proteins were detected in the SMGs of diabetic mice and HG-treated SMG cells. In diabetic SMGs, dynamin-related protein 1 (DRP1) was upregulated, whereas mitofusin-2 was downregulated both in vivo and in vitro. Shortened mitochondria and impaired mitochondrial functions were observed in the HG group. A DRP1-specific inhibitor, mdivi-1, suppressed mitochondrial fission and mitophagy, as well as restored mitochondrial functions in the HG condition. Moreover, the interaction of F-actin and DRP1 was enhanced in the diabetic group. Inhibiting F-actin with cytochalasin D repaired the injured effects of HG on mitochondrial dynamics and functions. Conversely, the F-actin-polymerization-inducer jasplakinolide aggravated mitochondrial fission and dysfunction. CONCLUSIONS: F-actin contributes to HG-evoked mitochondrial fission by interacting with DRP1, which induces mitophagy and impairs mitochondrial function in SMG cells, ultimately damaging the SMG.

4.
MycoKeys ; 104: 71-89, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665969

RESUMO

The genus Favolaschia within the family Mycenaceae is characterised by the gelatinous basidiomata with poroid hymenophore and most species inhabit monocotyledonous plants. In this study, many samples covering a wide geographic range in China were examined morphologically and phylogenetically using concatenated ITS1-5.8S-ITS2-nLSU sequence data. Three new species clustering in Favolaschiasect.Anechinus, namely Favolaschiaimbricata, F.miscanthi and F.sinarundinariae, are described. Favolaschiaimbricata is characterised by imbricate basidiomata with pale grey to greyish colour when fresh and broadly ellipsoid basidiospores measuring 7-9 × 5-6.8 µm; F.miscanthi is characterised by satin white basidiomata when fresh, broadly ellipsoid basidiospores measuring 7.5-10 × 5.5-7 µm and inhabit rotten Miscanthus; F.sinarundinariae is characterised by greyish-white basidiomata when fresh, dark grey near the base upon drying, broadly ellipsoid to subglobose basidiospores measuring 7-9 × 5-7 µm and inhabit dead Sinarundinaria. The differences amongst the new species and their morphologically similar and phylogenetically related species are discussed. In addition, an updated key to 19 species of Favolaschia found in China is provided.

5.
World J Gastrointest Oncol ; 16(4): 1344-1360, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660669

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant cancer, characterized by frequent mucin overexpression. MUC1 has been identified as a critical oncogene in the progression of CCA. However, the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still incomplete. AIM: To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA patients. METHODS: Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins, complemented by bioinformatic analyses. Subsequent validations were conducted through spatial transcriptomics and immunohistochemistry. The construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm, which was further confirmed by independent cohorts and diverse data types. RESULTS: CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased invasiveness. MUC5AC-high cells were found to promote CCA progression through WNT signaling. MUC5B-high cells exhibited robust cellular oxidation activities, leading to resistance against antitumoral treatments. MUC13-high cells were observed to secret chemokines, recruiting and transforming macrophages into the M2-polarized state, thereby suppressing antitumor immunity. MUC16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with neutrophils. Utilizing the expression levels of these mucins, a risk factor evaluation formula for CCA was developed and validated across multiple cohorts. CCA samples with higher risk factors exhibited stronger metastatic potential, chemotherapy resistance, and poorer prognosis. CONCLUSION: Our study elucidates the functional mechanisms through which mucins contribute to CCA development, and provides tools for risk stratification in CCA.

6.
Sci Rep ; 14(1): 8375, 2024 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600248

RESUMO

Exhausted CD8+ T lymphocytes and tumor-associated macrophages play critical roles in determining cancer prognosis and the efficacy of immunotherapy. Our study revealed a negative correlation between exhausted CD8+ T lymphocytes and prognosis in thyroid carcinoma (THCA). Consensus clustering divided patients into two subgroups of exhaustion with different prognoses, as defined by marker genes of exhausted CD8+ T cells. Subsequently, we constructed an eight-gene prognostic signature, and developed a risk score named the exhaustion-related gene score (ERGS) to forecast both prognosis and immunotherapy response in THCA. Bulk RNA sequencing analysis revealed a higher prevalence of M2 macrophages, indicative of an immunosuppressive tumor microenvironment (TME), in the high-ERGS group. Single-cell RNA sequencing showed that SPP1+ macrophages and CD14+ monocytes infiltrations were positively associated with higher ERGS. Functionally, it was determined that SPP1+ macrophages exert an immunosuppressive role, while CD14+ monocytes were implicated in promoting tumor progression and angiogenesis. Analysis of cell-cell interactions between SPP1+ macrophages and T cells highlighted the activation of the SPP1-CD44 and MIF-CD74 axes, both of which could foster an immunosuppressive TME. Therapeutic strategies that target SPP1+ macrophages, CD14+ monocytes, and the SPP1-CD44 and MIF-CD74 axes may potentially improve the prognosis and amplify the immunotherapy response in THCA patients.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias da Glândula Tireoide , Humanos , Exaustão das Células T , Prognóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/terapia , Imunoterapia , Imunossupressores , RNA , Microambiente Tumoral/genética
7.
Fish Shellfish Immunol ; 149: 109564, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631439

RESUMO

Grass carp reovirus (GCRV) infections and hemorrhagic disease (GCHD) outbreaks are typically seasonally periodic and temperature-dependent, yet the molecular mechanism remains unclear. Herein, we depicted that temperature-dependent IL-6/STAT3 axis was exploited by GCRV to facilitate viral replication via suppressing type Ⅰ IFN signaling. Combined multi-omics analysis and qPCR identified IL-6, STAT3, and IRF3 as potential effector molecules mediating GCRV infection. Deploying GCRV challenge at 18 °C and 28 °C as models of resistant and permissive infections and switched to the corresponding temperatures as temperature stress models, we illustrated that IL-6 and STAT3 expression, genome level of GCRV, and phosphorylation of STAT3 were temperature dependent and regulated by temperature stress. Further research revealed that activating IL-6/STAT3 axis enhanced GCRV replication and suppressed the expression of IFNs, whereas blocking the axis impaired viral replication. Mechanistically, grass carp STAT3 inhibited IRF3 nuclear translocation via interacting with it, thus down-regulating IFNs expression, restraining transcriptional activation of the IFN promoter, and facilitating GCRV replication. Overall, our work sheds light on an immune evasion mechanism whereby GCRV facilitates viral replication by hijacking IL-6/STAT3 axis to down-regulate IFNs expression, thus providing a valuable reference for targeted prevention and therapy of GCRV.

8.
Huan Jing Ke Xue ; 45(5): 2962-2970, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629557

RESUMO

The sediment and soil in the Juma River channel pose a risk of pollution to the downstream ecological environment of Beijing and Xiong'an New Area. To address this issue, sediments and soil samples were collected along the river from the source to the Zhangfang outlet. The samples were further divided into three types:main stream sediment (29 samples), riverbank soil (27 samples), and farmland soil (26 samples). Enrichment factor analysis and the potential ecological risk index were employed to investigate the ecological risk. The results showed that the average concentrations of Cd, Hg, Pb, Zn, and Cu in the river sediment and soil in the study area were higher than those in the Baiyangdian Lake sediment and the surface soil of Hebei Province, whereas the concentrations of As, Cr, and Ni were relatively lower. The ranking of heavy metal pollution levels from high to low were Cd > Hg > Pb > Zn > Cu > Cr > Ni > As. The comprehensive ecological risk index showed that farmland soil and riverbank soil were mainly at a slight risk, followed by a moderate risk. The potential ecological risk of the main stream sediment was mainly moderate, severe, and extremely severe, accounting for 35.5%, 24.1%, and 24.1%, respectively, and the main contributing factors of the risk were Cd and Hg. The results of multivariate statistical analysis indicated that the main pollution sources of Cd, Pb, Zn, and Cu were industrial and mining activities. Cr, Ni, and As were mainly controlled by the weathering of the parent rock, and As was also influenced by agricultural activities. Hg was controlled by composite pollution sources such as industrial and mining activities, parent rock weathering, and atmospheric dust fall. Overall, the risk of heavy metal in the soil of the research area was generally at a slight level. However, there was a significant enrichment of Cd and other heavy metal in the sediment of the Taiyu-Sigezhuang-Pengtou River. This river section should be the focus of environmental monitoring, river dredging, and governance.

9.
Ibrain ; 10(1): 106-110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38682014

RESUMO

Similar reports in the past pay less attention to the anesthetic management of these patients. We reported a 46-year-old man who suffered from hypertensive cerebral apoplexy 5 months ago and accepted C7 nerve transfer to improve the central spastic paralysis in the right upper limb. After careful evaluation and anesthesia management before anesthesia, the operation was successfully completed under general anesthesia. The patient was cured and discharged without complications. The anesthesia management of C7 nerve transfer should choose appropriate operation opportunities for patients according to the type of stroke, improve the preoperative preparation, and form a multidisciplinary diagnosis and treatment.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38652005

RESUMO

Two Gram-negative, aerobic, rod-shaped bacterial strains, 7MK25T and 6Y81T, were isolated from forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China. Based on the results of 16S rRNA gene sequence analysis, strain 7MK25T showed the highest similarity (93.6 %) to Methyloferula stellata AR4T, followed by Bosea thiooxidans DSM 9653T (93.3 %). Strain 6Y81T had the highest similarity of 97.9 % to Lichenibacterium minor RmlP026T, followed by Lichenibacterium ramalinae RmlP001T (97.2 %). Phylogenomic analysis using the UBCG and PhyloPhlAn methods consistently showed that strain 7MK25T formed a sister clade to Boseaceae, while strain 6Y81T formed an independent clade within the genus Lichenibacterium, both in the order Hyphomicrobiales. The digital DNA-DNA hybridization and average nucleotide identity values between strains 7MK25T, 6Y81T and their close relatives were in the ranges of 19.1-29.9 % and 72.5-85.5 %, respectively. The major fatty acids of 7MK25T were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c), C19 : 0 cyclo ω8c, C16 : 0 and C17 : 0 cyclo, while those of 6Y81T were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c), C16 : 0 and C16 : 0 3-OH. Strains 7MK25T and 6Y81T took diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine as their dominant polar lipids, and Q-10 as their major respiratory quinone. On the basis of phenotypic and phylogenetic data, strain 7MK25T is proposed to represent a novel species of a novel genus with name Terrirubrum flagellatum gen. nov., sp. nov., within a novel family Terrirubraceae fam. nov., with 7MK25T (=KCTC 62738T=GDMCC 1.1452T) as its type strain. Strain 6Y81T represents a novel species in the genus Lichenibacterium, for which the name Lichenibacterium dinghuense sp. nov. (type strain 6Y81T=KACC 21 727T=GDMCC 1.2176T) is proposed. Rhodoblastaceae fam. nov. with Rhodoblastus as the type genus is also proposed to solve the non-monophylectic problem of the family Roseiarcaceae.


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Florestas , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Microbiologia do Solo , RNA Ribossômico 16S/genética , China , DNA Bacteriano/genética , Ubiquinona
11.
J Am Chem Soc ; 146(18): 12743-12749, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38652821

RESUMO

Aqueous batteries, with the advantages of high safety and low cost, are highly promising for large-scale energy storage. However, freezing of the aqueous electrolyte limits the low-temperature operation. Here, we propose and achieve a highly dispersed solvation structure in the electrolyte by coupling nonaggregated Cl- anions, which reduces the water cluster size and prevents the solidification of the aqueous electrolyte until -136.3 °C. The low-temperature LiCl electrolyte exhibits a high ionic conductivity (1.0 mS cm-1) at -80 °C and enables a stable low-temperature Ag/AgCl reference electrode at -50 °C. Moreover, the polyaniline-based battery can work at an extremely low temperature of -100 °C and shows superior cycling performance of 4000 cycles at -40 °C with 95.7% capacity retention. This work elucidates the correlation between the anion effect and the thermodynamic transition of the electrolyte, offering a novel approach for designing low-temperature electrolytes.

12.
Medicine (Baltimore) ; 103(14): e37720, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579026

RESUMO

RATIONALE: Epistaxis is one of the common emergencies in otolaryngology. There are many causes of epistaxis, but reports of epistaxis due to nasal foreign bodies like leeches are rare. PATIENT CONCERNS: A 55-year-old male presented with "repeated epistaxis for over 20 days." Nasal endoscopy revealed a live leech in the olfactory area of the left nostril. DIAGNOSES: The patient was diagnosed with epistaxis caused by a live leech in the nasal cavity. INTERVENTIONS: Under nasal endoscopy, the leech was grasped with a vascular clamp and removed from the nasal cavity. The leech measured 8 cm in length. Hemostasis was achieved using a gelatin sponge at the wound site, and the nasal cavity was packed with Vaseline gauze. OUTCOMES: The live leech was removed via nasal endoscopy. Two days later, the Vaseline gauze packing was removed, and the patient experienced no further nasal bleeding. CONCLUSION: Live leeches in the nasal cavity can cause epistaxis. Nasal endoscopic removal of the live leech is an effective treatment. LESSON: There are many causes of epistaxis, which are nonspecific and prone to missed or incorrect diagnosis. In patients with a history of fieldwork or direct contact with leeches who present with recurrent nasal bleeding, the possibility of epistaxis caused by a live leech should be considered, and timely and effective treatment should be provided.


Assuntos
Epistaxe , Sanguessugas , Animais , Humanos , Masculino , Pessoa de Meia-Idade , Endoscopia , Epistaxe/etiologia , Epistaxe/terapia , Epistaxe/diagnóstico , Cavidade Nasal , Nariz , Vaselina
13.
Mol Cell Endocrinol ; 588: 112225, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38570133

RESUMO

Although Liraglutide (Lira) increases serum irisin levels in type 2 diabetes mellitus (T2DM), it is unclear whether it induces expression of uncoupling protein 1 (UCP1) of adipocytes via promoting irisin secretion from skeletal muscle. Male T2DM rats were treated with 0.4 mg/kg/d Lira twice a day for 8 weeks, and the protein expression of phosphorylated AMP kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase 1 (p-ACC1) and UCP1 in white adipose tissues were detected. Differentiated C2C12 cells were treated with palmitic acid (PA) and Lira to detect the secretion of irisin. Differentiated 3T3-L1 cells were treated with irisin, supernatant from Lira-treated C2C12 cells, Compound C or siAMPKα1, the triglyceride (TG) content and the related gene expression were measured. The transcriptome in irisin-treated differentiated 3T3-L1 cells was analyzed. Lira elevated serum irisin levels, decreased the adipocyte size and increased the protein expression of UCP1, p-AMPK and p-ACC1 in WAT. Moreover, it promoted the expression of PGC1α and FNDC5, the secretion of irisin in PA-treated differentiated C2C12 cells. The irisin and supernatant decreased TG synthesis and promoted the expression of browning- and lipolysis-related genes in differentiated 3T3-L1 cells. While Compound C and siAMPKα1 blocked AMPK activities and expression, irisin partly reversed the pathway. Finally, the transcriptome analysis indicated that differently expressed genes are mainly involved in browning and lipid metabolism. Overall, our findings showed that Lira modulated muscle-to-adipose signaling pathways in diabetes via irisin-mediated AMPKα/ACC1/UCP1/PPARα pathway. Our results suggest a new mechanism for the treatment of T2DM by Lira.


Assuntos
Células 3T3-L1 , Adipócitos , Fibronectinas , Lipólise , Liraglutida , Proteína Desacopladora 1 , Animais , Fibronectinas/metabolismo , Fibronectinas/genética , Camundongos , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Masculino , Adipócitos/metabolismo , Adipócitos/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Liraglutida/farmacologia , Ratos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Ratos Sprague-Dawley , Diferenciação Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos
14.
J Mol Cell Cardiol ; 190: 62-75, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583797

RESUMO

Intimal hyperplasia is a complicated pathophysiological phenomenon attributable to in-stent restenosis, and the underlying mechanism remains unclear. Interleukin enhancer-binding factor 3 (ILF3), a double-stranded RNA-binding protein involved in regulating mRNA stability, has been recently demonstrated to assume a crucial role in cardiovascular disease; nevertheless, its impact on intimal hyperplasia remains unknown. In current study, we used samples of human restenotic arteries and rodent models of intimal hyperplasia, we found that vascular smooth muscle cell (VSMC) ILF3 expression was markedly elevated in human restenotic arteries and murine ligated carotid arteries. SMC-specific ILF3 knockout mice significantly suppressed injury induced neointimal formation. In vitro, platelet-derived growth factor type BB (PDGF-BB) treatment elevated the level of VSMC ILF3 in a dose- and time-dependent manner. ILF3 silencing markedly inhibited PDGF-BB-induced phenotype switching, proliferation, and migration in VSMCs. Transcriptome sequencing and RNA immunoprecipitation sequencing depicted that ILF3 maintained its stability upon binding to the mRNA of the high-mobility group box 1 protein (HMGB1), thereby exerting an inhibitory effect on the transcription of dual specificity phosphatase 16 (DUSP16) through enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3). Therefore, the results both in vitro and in vivo indicated that the loss of ILF3 in VSMC ameliorated neointimal hyperplasia by regulating the STAT3/DUSP16 axis through the degradation of HMGB1 mRNA. Our findings revealed that vascular injury activates VSMC ILF3, which in turn promotes intima formation. Consequently, targeting specific VSMC ILF3 may present a potential therapeutic strategy for ameliorating cardiovascular restenosis.


Assuntos
Proteína HMGB1 , Hiperplasia , Camundongos Knockout , Músculo Liso Vascular , Miócitos de Músculo Liso , Proteínas do Fator Nuclear 90 , Estabilidade de RNA , Fator de Transcrição STAT3 , Túnica Íntima , Animais , Humanos , Masculino , Camundongos , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Regulação da Expressão Gênica , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Neointima/metabolismo , Neointima/patologia , Proteínas do Fator Nuclear 90/metabolismo , Proteínas do Fator Nuclear 90/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Túnica Íntima/metabolismo , Túnica Íntima/patologia
15.
Int Immunopharmacol ; 133: 112066, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38615377

RESUMO

Acevaltrate is a natural product isolated from the roots of Valeriana glechomifolia F.G.Mey. (Valerianaceae) and has been shown to exhibit anti-cancer activity. However, the mechanism by which acevaltrate inhibits tumor growth is not fully understood. We here demonstrated the effect of acevaltrate on hypoxia-inducible factor-1α (HIF-1α) expression. Acevaltrate showed a potent inhibitory activity against HIF-1α induced by hypoxia in various cancer cells. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently. Further analysis revealed that acevaltrate inhibited HIF-1α protein synthesis and promoted degradation of HIF-1α protein, without affecting the expression level of HIF-1α mRNA. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and eIF4E binding protein-1 (4E-BP1) were significantly suppressed by acevaltrate. In addition, acevaltrate promoted apoptosis and inhibited proliferation, which was potentially mediated by suppression of HIF-1α. We also found that acevaltrate administration inhibited tumor growth in mouse xenograft model. Taken together, these results suggested that acevaltrate was a potent inhibitor of HIF-1α and provided a new insight into the mechanisms of acevaltrate against cancers.


Assuntos
Apoptose , Proliferação de Células , Subunidade alfa do Fator 1 Induzível por Hipóxia , Serina-Treonina Quinases TOR , Valeriana , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Humanos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Valeriana/química , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos , Camundongos Nus , Camundongos Endogâmicos BALB C , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico
16.
Sci Rep ; 14(1): 6814, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514736

RESUMO

The present study aims to assess the treatment outcome of patients with diabetes and tuberculosis (TB-DM) at an early stage using machine learning (ML) based on electronic medical records (EMRs). A total of 429 patients were included at Chongqing Public Health Medical Center. The random-forest-based Boruta algorithm was employed to select the essential variables, and four models with a fivefold cross-validation scheme were used for modeling and model evaluation. Furthermore, we adopted SHapley additive explanations to interpret results from the tree-based model. 9 features out of 69 candidate features were chosen as predictors. Among these predictors, the type of resistance was the most important feature, followed by activated partial throm-boplastic time (APTT), thrombin time (TT), platelet distribution width (PDW), and prothrombin time (PT). All the models we established performed above an AUC 0.7 with good predictive performance. XGBoost, the optimal performing model, predicts the risk of treatment failure in the test set with an AUC 0.9281. This study suggests that machine learning approach (XGBoost) presented in this study identifies patients with TB-DM at higher risk of treatment failure at an early stage based on EMRs. The application of a convenient and economy EMRs based on machine learning provides new insight into TB-DM treatment strategies in low and middle-income countries.


Assuntos
Diabetes Mellitus , Humanos , Comorbidade , Falha de Tratamento , Registros Eletrônicos de Saúde , Aprendizado de Máquina
17.
Commun Biol ; 7(1): 300, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461326

RESUMO

Diabetic foot ulcer (DFU), a serious complication of diabetes, remains a clinical challenge. MicroRNAs affect inflammation and may have therapeutic value in DFU. Here, we find that an miR-221-3p mimic reduces the inflammatory response and increases skin wound healing rates in a mouse model of diabetes, whereas miR-221-3p knockout produced the opposite result. In human keratinocytes cells, miR-221-3p suppresses the inflammatory response induced by high glucose. The gene encoding DYRK1A is a target of miR-221-3p. High glucose increases the expression of DYRK1A, but silencing DYRK1A expression decreases high glucose-induced inflammatory cytokine release via dephosphorylation of STAT3, a substrate of DYRK1A. Application of miR-221-3p mimic to human keratinocytes cells not only decreases DYRK1A expression but also inhibits high glucose-induced production of inflammatory cytokines to promote wound healing. This molecular mechanism whereby miR-221-3p regulates inflammation through the DYRK1A/STAT3 signaling pathway suggests targets and therapeutic approaches for treating DFU.


Assuntos
Diabetes Mellitus , Pé Diabético , MicroRNAs , Animais , Humanos , Camundongos , Citocinas/metabolismo , Diabetes Mellitus/metabolismo , Pé Diabético/genética , Glucose/metabolismo , Inflamação/genética , Inflamação/metabolismo , Queratinócitos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais/fisiologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Cicatrização/genética , Quinases Dyrk/metabolismo
18.
Food Chem ; 448: 139060, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38537548

RESUMO

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), a type of fatty acid that has many health benefits, are of increasing concern. Herein, we developed a method for the rapid esterification and enrichment of ω-3 PUFAs in eggs, which includes microwave-assisted esterification (MAE) and electrically enhanced solid-phase microextraction (EE-SPME). Combined with gas chromatographic, efficient detection of ω-3 PUFAs was achieved in eggs. Under microwave radiation, the esterification efficiency exhibited a significant increase ranging from 5.06 to 10.65 times. The EE-SPME method reduced extraction time from 50 to 15 min. In addition, improvements in extractive fiber coating materials were explored, which ensured efficient extraction of ω-3 PUFAs. Under the optimal conditions, the method displayed a low detection limit (1.01-1.54 µg L-1), good recoveries (85.82%-106.01%), and wide linear range (7.5-1000 µg L-1), which was successfully applied to determine ω-3 PUFAs in real egg samples.

19.
J Colloid Interface Sci ; 665: 133-143, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38520930

RESUMO

Anion exchange membranes (AEMs) are the heart of alkaline fuel cells and water electrolysis, and have made a great progress in recent years. However, AEMs are still unable to satisfy the needs of high conductivity and stability, hindering their widespread commercialization. Side chain regulations have been widely used to prepare highly conductive and durable AEMs. Here, we construct a series of polyaromatic AEMs grafted with fluorinated cation side chains and cation-free alkyl chains with different end groups to explore the polar discrimination of side chains on membrane performance. This work demonstrates that AEMs grafting the cation side chains with superhydrophobic fluorine pendent and alkyl side chains with hydrophilic pendent enhance water content and ion conductivity. This is due to the strong immiscibility between the hydrophilic and hydrophobic head groups which promotes the establishments of microphase separation and ion highways. Specifically, poly(binaphthyl-co-terphenyl piperidinium) containing fluorinated piperidinium side chains and alkyl chains with methoxy pendent (QBNTP-QFM) possesses a satisficed OH- conductivity (170.6 mS cm-1 at 80 °C) and can tolerate 5 M hot NaOH for 2100 h with only 3.4 % conductivity loss. Expectedly, the single cell with QBNTP-QFM yields a prominent maximum power density of 1.62 W cm-2 and the water electrolysis cell with QBNTP-QFM achieves a pronounced current density of 3.0 A cm-2 at 1.8 V, both cells also display a prominent durability for 120 h operation. The results prove that this side chain optimization can improve ion conductivity and is a promising method for AEM development.

20.
Medicine (Baltimore) ; 103(9): e37304, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428852

RESUMO

RATIONALE: Botrychium ternatum ((Thunb.) Sw.), a traditional Chinese medicine, is known for its therapeutic properties in clearing heat, detoxifying, cough suppression, and phlegm elimination. It has been extensively used in clinics for the treatment of many inflammation-related diseases. Currently, there are no documented cases of rhabdomyolysis resulting from Botrychium ternatum intoxication. PATIENT CONCERNS: A 57-year-old male presented with a complaint of low back discomfort accompanied by tea-colored urine lasting for 4 days. The patient also exhibited markedly increased creatine phosphate kinase and myoglobin levels. Prior to the onset of symptoms, the patient consumed 50 g of Botrychium ternatum to alleviate pharyngodynia. DIAGNOSES: The patient was diagnosed with rhabdomyolysis due to Botrychium ternatum intoxication. INTERVENTIONS: The patient underwent a substantial volume of fluid resuscitation, diuresis, and alkalization of urine, as well as correction of the acid-base balance and electrolyte disruption. OUTCOMES: Following a 10-day treatment plan involving massive fluid resuscitation, diuresis, and alkalization of urine, the patient showed notable improvement in his lower back pain and reported the absence of any discomfort. Following reexamination, the levels of creatine phosphate kinase and myoglobin were restored to within the normal ranges. Additionally, no abnormalities were detected in liver or renal function. As a result, the patient was considered eligible for discharge and was monitored. CONCLUSIONS: Botrychium ternatum intoxication was associated with the development of rhabdomyolysis. To manage this condition, it is recommended that patients provide massive fluid resuscitation, diuresis, alkalization of urine, and other appropriate therapeutic interventions. LESSON: Currently, there are no known cases of rhabdomyolysis resulting from Botrychium ternatum intoxication. However, it is important to consider the potential occurrence of rhabdomyolysis resulting from Botrychium ternatum intoxication when there is a correlation between the administration of Botrychium ternatum and the presence of muscular discomfort in the waist or throughout the body, along with tea-colored urine. Considering the levels of creatine phosphate kinase and myoglobin, the diagnosis or exclusion of rhabdomyolysis caused by Botrychium ternatum intoxication should be made, and suitable treatment should be administered accordingly.


Assuntos
Mioglobina , Rabdomiólise , Masculino , Humanos , Pessoa de Meia-Idade , Fosfocreatina , Rabdomiólise/induzido quimicamente , Rabdomiólise/diagnóstico , Hidratação/efeitos adversos , Creatina Quinase , Chá
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA