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1.
Muscle Nerve ; 70(2): 210-216, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38828855

RESUMO

INTRODUCTION/AIMS: The current diagnosis of ulnar neuropathy at the elbow (UNE) relies mainly on the clinical presentation and nerve electrodiagnostic (EDX) testing, which can be uncomfortable and yield false negatives. The aim of this study was to investigate the diagnostic value of conventional ultrasound, shear wave elastography (SWE), and superb microvascular imaging (SMI) in diagnosing UNE. METHODS: We enrolled 40 patients (48 elbows) with UNE and 48 healthy volunteers (48 elbows). The patients were categorized as having mild, moderate or severe UNE based on the findings of EDX testing. The cross-sectional area (CSA) was measured using conventional ultrasound. Ulnar nerve (UN) shear wave velocity (SWV) and SMI were performed in a longitudinal plane. RESULTS: Based on the EDX findings, UNE severity was graded as mild in 4, moderate in 10, and severe in 34. The patient group showed increased ulnar nerve CSA and stiffness at the site of maximal enlargement (CSA mean at the site of max enlargement [CSAmax] and SWV mean at the site of max enlargement [SWVmax]), ulnar nerve CSA ratio, and stiffness ratio (elbow-to-upper arm), compared with the control group (p < .001). Furthermore, the severe UNE group showed higher ulnar nerve CSAmax and SWVmax compared with the mild and moderate UNE groups (p < .001). The cutoff values for diagnosis of UNE were 9.5 mm2 for CSAmax, 3.06 m/s for SWVmax, 2.00 for CSA ratio, 1.36 for stiffness ratio, and grade 1 for SMI. DISCUSSION: Our findings suggest that SWE and SMI are valuable diagnostic tools for the diagnosis and assessment of severity of UNE.


Assuntos
Técnicas de Imagem por Elasticidade , Cotovelo , Nervo Ulnar , Neuropatias Ulnares , Ultrassonografia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Técnicas de Imagem por Elasticidade/métodos , Neuropatias Ulnares/diagnóstico por imagem , Neuropatias Ulnares/fisiopatologia , Cotovelo/diagnóstico por imagem , Ultrassonografia/métodos , Idoso , Nervo Ulnar/diagnóstico por imagem , Nervo Ulnar/fisiopatologia , Microvasos/diagnóstico por imagem , Eletrodiagnóstico/métodos
2.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167304, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878830

RESUMO

Pancreatic cancer (PC) responds weakly to conventional immunotherapy. RNA N6-methyladenosine (m6A) modification has an essential role in the immune response, while its potential role in PC tumor microenvironment (TME) immune cell infiltration remains unknown. In this study, we thoroughly assessed the m6A modification patterns of 472 PC samples using 19 m6A regulators, and we systematically correlated these modification patterns with TME immune cell infiltration characteristics. We also created the m6Ascore and evaluated the m6A modification patterns of individual tumors, identified three different m6A modification patterns, and explored the role of the important m6A "writer" RBM15 in the regulation of macrophage function in PC. Two independent PC cohorts confirmed that patients with higher m6Ascore showed significant survival benefit. We verified that knockdown of RBM15 has the ability to inhibit PC growth and to promote macrophage infiltration and enhance phagocytosis of PC cells by macrophages. In conclusion, m6A modifications play a non-negligible role in the formation of TME diversity and complexity in PC. We reveal that inhibition of RBM15 suppresses PC development and modulates macrophage phagocytosis, and provide a more effective immunotherapeutic strategy for PC.

4.
Bioorg Chem ; 149: 107507, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38850778

RESUMO

Opioids are currently the most effective and widely used painkillers in the world. Unfortunately, the clinical use of opioid analgesics is limited by serious adverse effects. Many researchers have been working on designing and optimizing structures in search of novel µ opioid receptor(MOR) agonists with improved analgesic activity and reduced incidence of adverse effects. There are many strategies to develop MOR drugs, mainly focusing on new low efficacy agonists (potentially G protein biased agonists), MOR agonists acting on different Gα subtype, targeting opioid receptors in the periphery, acting on multiple opioid receptor, and targeting allosteric sites of opioid receptors, and others. This review summarizes the design methods, clinical applications, and structure-activity relationships of small-molecule agonists for MOR based on these different design strategies, providing ideas for the development of safer novel opioid ligands with therapeutic potential.


Assuntos
Analgésicos Opioides , Receptores Opioides mu , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Humanos , Relação Estrutura-Atividade , Analgésicos Opioides/farmacologia , Analgésicos Opioides/química , Animais , Estrutura Molecular
5.
Mol Biol Rep ; 51(1): 720, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824268

RESUMO

BACKGROUND: Tumor-associated macrophages (TAM) exert a significant influence on the progression and heterogeneity of various subtypes of breast cancer (BRCA). However, the roles of heterogeneous TAM within BRCA subtypes remain unclear. Therefore, this study sought to elucidate the role of TAM across the following three BRCA subtypes: triple-negative breast cancer, luminal, and HER2. MATERIALS AND METHODS: This investigation aimed to delineate the variations in marker genes, drug sensitivity, and cellular communication among TAM across the three BRCA subtypes. We identified specific ligand-receptor (L-R) pairs and downstream mechanisms regulated by VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Experimental verification of these pairs was conducted by co-culturing macrophages with three subtypes of BRCA cells. RESULTS: Our findings reveal the heterogeneity of macrophages within the three BRCA subtypes, evidenced by variations in marker gene expression, composition, and functional characteristics. Notably, heterogeneous TAM were found to promote invasive migration and epithelial-mesenchymal transition (EMT) in MDA-MB-231, MCF-7, and SKBR3 cells, activating NF-κB pathway via P38 MAPK, TGF-ß1, and AKT, respectively, through distinct VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Inhibition of these specific L-R pairs effectively reversed EMT, migration, and invasion of each cancer cells. Furthermore, we observed a correlation between ligand gene expression and TAM sensitivity to anticancer drugs, suggesting a potential strategy for optimizing personalized treatment guidance. CONCLUSION: Our study highlights the capacity of heterogeneous TAM to modulate biological functions via distinct pathways mediated by specific L-R pairs within diverse BRCA subtypes. This study might provide insights into precision immunotherapy of different subtypes of BRCA.


Assuntos
Neoplasias da Mama , Transição Epitelial-Mesenquimal , Macrófagos Associados a Tumor , Humanos , Feminino , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Análise de Célula Única/métodos , Células MCF-7 , Movimento Celular/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Análise de Sequência de RNA/métodos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Transdução de Sinais/genética , Microambiente Tumoral/genética
6.
Curr Oncol ; 31(6): 3073-3085, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38920718

RESUMO

Canada's decentralized healthcare system may lead to regional disparities in survival among Canadians diagnosed with central nervous system (CNS) tumours. We identified 50,670 patients diagnosed with a first-ever primary CNS tumour between 2008 and 2017 with follow-up until 31 December 2017. We selected the four highest incidence histologies and used proportional hazard regression to estimate hazard ratios (HRs) for five regions (British Columbia, Prairie Provinces, Ontario, Atlantic Provinces and the Territories), adjusting for sex, tumour behaviour and patient age. Ontario had the best survival profile for all histologies investigated. The Atlantic Provinces had the highest HR for glioblastoma (HR = 1.26, 95% CI: 1.18-1.35) and malignant glioma not otherwise specified (NOS) (Overall: HR = 1.87, 95% CI:1.43-2.43; Pediatric population: HR = 2.86, 95% CI: 1.28-6.39). For meningioma, the Territories had the highest HR (HR = 2.44, 95% CI: 1.09-5.45) followed by the Prairie Provinces (HR = 1.52, 95% CI: 1.38-1.67). For malignant unclassified tumours, the highest HRs were in British Columbia (HR = 1.45, 95% CI: 1.22-1.71) and the Atlantic Provinces (HR = 1.40, 95% CI: 1.13-1.74). There are regional differences in the survival of CNS patients at the population level for all four specific histological types of CNS tumours investigated. Factors contributing to these observed regional survival differences are unknown and warrant further investigation.


Assuntos
Neoplasias do Sistema Nervoso Central , Humanos , Neoplasias do Sistema Nervoso Central/mortalidade , Canadá/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Adolescente , Criança , Pré-Escolar , Lactente
7.
Planta ; 260(1): 33, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896325

RESUMO

MAIN CONCLUSION: γ-Aminobutyric acid alleviates acid-aluminum toxicity to roots associated with enhanced antioxidant metabolism as well as accumulation and transportation of citric and malic acids. Aluminum (Al) toxicity has become the main limiting factor for crop growth and development in acidic soils and is further being aggravated worldwide due to continuous industrial pollution. The current study was designed to examine effects of GABA priming on alleviating acid-Al toxicity in terms of root growth, antioxidant defense, citrate and malate metabolisms, and extensive metabolites remodeling in roots under acidic conditions. Thirty-seven-day-old creeping bentgrass (Agrostis stolonifera) plants were used as test materials. Roots priming with or without 0.5 mM GABA for 3 days were cultivated in standard nutrient solution for 15 days as control or subjected to nutrient solution containing 5 mM AlCl3·6H2O for 15 days as acid-Al stress treatment. Roots were sampled for determinations of root characteristics, physiological and biochemical parameters, and metabolomics. GABA priming significantly alleviated acid-Al-induced root growth inhibition and oxidative damage, despite it promoted the accumulation of Al in roots. Analysis of metabolomics showed that GABA priming significantly increased accumulations of organic acids, amino acids, carbohydrates, and other metabolites in roots under acid-Al stress. In addition, GABA priming also significantly up-regulated key genes related to accumulation and transportation of malic and citric acids in roots under acid-Al stress. GABA-regulated metabolites participated in tricarboxylic acid cycle, GABA shunt, antioxidant defense system, and lipid metabolism, which played positive roles in reactive oxygen species scavenging, energy conversion, osmotic adjustment, and Al ion chelation in roots.


Assuntos
Agrostis , Alumínio , Antioxidantes , Malatos , Raízes de Plantas , Ácido gama-Aminobutírico , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Antioxidantes/metabolismo , Ácido gama-Aminobutírico/metabolismo , Alumínio/toxicidade , Agrostis/efeitos dos fármacos , Agrostis/metabolismo , Agrostis/fisiologia , Malatos/metabolismo , Ácido Cítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos
9.
FEBS Lett ; 598(13): 1591-1604, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38724485

RESUMO

Inhibition of the cyclic-AMP degrading enzyme phosphodiesterase type 4 (PDE4) in the brains of animal models is protective in Alzheimer's disease (AD). We show for the first time that enzymes from the subfamily PDE4D not only colocalize with beta-amyloid (Aß) plaques in a mouse model of AD but that Aß directly associates with the catalytic machinery of the enzyme. Peptide mapping suggests that PDE4D is the preferential PDE4 subfamily for Aß as it possesses a unique binding site. Intriguingly, exogenous addition of Aß to cells overexpressing the PDE4D5 longform caused PDE4 activation and a decrease in cAMP. We suggest a novel mechanism where PDE4 longforms can be activated by Aß, resulting in the attenuation of cAMP signalling to promote loss of cognitive function in AD.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , AMP Cíclico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Neurônios , Animais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Peptídeos beta-Amiloides/metabolismo , AMP Cíclico/metabolismo , Camundongos , Neurônios/metabolismo , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Ligação Proteica , Ativação Enzimática , Camundongos Transgênicos , Placa Amiloide/metabolismo , Placa Amiloide/patologia
10.
Biol Psychol ; 190: 108809, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38718883

RESUMO

In the mind of the beholder the personality and facial attractiveness of others are interrelated. However, how these specific properties are processed in the neurocognitive system and interact with each other while economic decisions are made is not well understood. Here, we combined the ultimatum game with EEG technology, to investigate how alleged personality traits and the perceived facial attractiveness of proposers of fair and unfair offers influence their acceptance by the responders. As expected, acceptance rate was higher for fair than unfair allocations. Overall, responders were more likely to accept proposals from individuals with higher facial attractiveness and with more positive personality traits. In ERPs, words denoting negative personality traits elicited larger P2 components than positive trait words, and more attractive faces elicited larger LPC amplitudes. Replicating previous findings, FRN amplitudes were larger to unfair than to fair allocations. This effect was diminished if the proposer's faces were attractive or associated with positive personality traits. Hence, facial attractiveness and the valence of personality traits seem to be evaluated independently and at different time points. Subsequent decision making about unfair offers is similarly influenced by high attractiveness and positive personality of the proposer, diminishing the negative response normally elicited by "unfair" proposals, possibly due a "reward" effect. In the ERPs to the proposals the effect of positive personality and attractiveness were seen in the FRN and P300 components but for positive personality traits the effect even preceded the FRN effect. Altogether, the present results indicate that both high facial attractiveness and alleged positive personality mitigate the effects of unfair proposals, with temporally overlapping but independent neurocognitive correlates.


Assuntos
Beleza , Tomada de Decisões , Eletroencefalografia , Potenciais Evocados , Jogos Experimentais , Personalidade , Humanos , Personalidade/fisiologia , Feminino , Masculino , Tomada de Decisões/fisiologia , Adulto Jovem , Potenciais Evocados/fisiologia , Adulto , Face , Reconhecimento Facial/fisiologia , Adolescente
11.
Int J Mol Sci ; 25(9)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38732221

RESUMO

Abdominal aortic aneurysm (AAA) has been recognized as a serious chronic inflammatory degenerative aortic disease in recent years. At present, there is no other effective intervention except surgical treatment for AAA. With the aging of the human population, its incidence is increasing year by year, posing a serious threat to human health. Modern studies suggest that vascular chronic inflammatory response is the core process in AAA occurrence and development. Inflammasome, a multiprotein complex located in the cytoplasm, mediates the expression of various inflammatory cytokines like interleukin (IL)-1ß and IL-18, and thus plays a pivotal role in inflammation regulation. Therefore, inflammasome may exert a crucial influence on the progression of AAA. This article reviews some mechanism studies to investigate the role of inflammasome in AAA and then summarizes several potential drugs targeting inflammasome for the treatment of AAA, aiming to provide new ideas for the clinical prevention and treatment of AAA beyond surgical methods.


Assuntos
Aneurisma da Aorta Abdominal , Inflamassomos , Aneurisma da Aorta Abdominal/metabolismo , Humanos , Inflamassomos/metabolismo , Animais , Inflamação/metabolismo
12.
Eur J Neurosci ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777332

RESUMO

Although the attractiveness of voices plays an important role in social interactions, it is unclear how voice attractiveness and social interest influence social decision-making. Here, we combined the ultimatum game with recording event-related brain potentials (ERPs) and examined the effect of attractive versus unattractive voices of the proposers, expressing positive versus negative social interest ("I like you" vs. "I don't like you"), on the acceptance of the proposal. Overall, fair offers were accepted at significantly higher rates than unfair offers, and high voice attractiveness increased acceptance rates for all proposals. In ERPs in response to the voices, their attractiveness and expressed social interests yielded early additive effects in the N1 component, followed by interactions in the subsequent P2, P3 and N400 components. More importantly, unfair offers elicited a larger Medial Frontal Negativity (MFN) than fair offers but only when the proposer's voice was unattractive or when the voice carried positive social interest. These results suggest that both voice attractiveness and social interest moderate social decision-making and there is a similar "beauty premium" for voices as for faces.

13.
J Environ Sci (China) ; 144: 148-158, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38802226

RESUMO

Humic acid (HA) is a typical refractory organic matter, so it is of great significance to investigate its effect on the performance of Anammox granular sludge. When the dosage of HA ≤ 50 mg/L, HA promotes the total nitrogen removal rate (NRR) to 1.45 kg/(m3·day). When HA was between 50 and 100 mg/L, the NRR of Anammox was stable. At this time, the adsorption of HA causes the sludge to gradually turn from red to brown, but the activities of heme and enzymes showed that its capacity was not affected. When HA levels reached 250 mg/L, the NRR dropped to 0.11 kg/(m3·day). Moderate HA levels promoted the release of extracellular polymeric substance (EPS), but excessive HA levels lead to a decrease in EPS concentrations. HA inhibited Anammox activity, which indirectly hindered the transmission of substrate and accumulated substrate toxicity. Although HA promoted the increase of heterotrophic microbial abundance in Anammox system, the microbial diversity decreased gradually. With the increase of HA concentration, the abundance of Candidatus_Brocadia, the main functional microorganism of Anammox system, decreased gradually, while the abundance of Candidatus_Kuenenia increased gradually.


Assuntos
Substâncias Húmicas , Nitrogênio , Esgotos , Eliminação de Resíduos Líquidos , Esgotos/microbiologia , Eliminação de Resíduos Líquidos/métodos , Reatores Biológicos/microbiologia , Microbiota , Anaerobiose
14.
Poult Sci ; 103(6): 103706, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38631227

RESUMO

Skeletal disorders can seriously threaten the health and the performance of poultry, such as tibial dyschondroplasia (TD) and osteoporosis (OP). Oligomeric proanthocyanidins (OPC) are naturally occurring polyphenolic flavonoid compounds that can be used as potential substances to improve the bone health and the growth performance of poultry. Eighty 7-day-old green-eggshell yellow feather layer chickens were randomly divided into 4 groups: basal diet and basal diet supplementation with 25, 50, and 100 mg/kg OPC. The results have indicated that the growth performance and bone parameters of chickens were significantly improved supplementation with OPC in vivo, including the bone volume (BV), the bone mineral density (BMD) and the activities of antioxidative enzymes, but ratio of osteoprotegerin (OPG)/receptor activator of NF-κB (RANK) ligand (RANKL) was decreased. Furthermore, primary bone marrow mesenchymal stem cells (BMSCs) and bone marrow monocytes/macrophages (BMMs) were successfully isolated from femur and tibia of chickens, and co-cultured to differentiate into osteoclasts in vitro. The osteogenic differentiation derived from BMSCs was promoted treatment with high concentrations of OPC (10, 20, and 40 µmol/L) groups in vitro, but emerging the inhibition of osteoclastogenesis by increasing the ratio of OPG/RANKL. In contrary, the osteogenic differentiation was also promoted treatment with low concentrations of OPC (2.5, 5, and 10 µmol/L) groups, but osteoclastogenesis was enhanced by decreasing the ratio of OPG/RANKL in vitro. In addition, OPG inhibits the differentiation and activity of osteoclasts by increasing the autophagy in vitro. Dietary supplementation of OPC can improve the growth performance of bone and alter the balance of osteoblasts and osteoclasts, thereby improving the bone health of chickens.


Assuntos
Ração Animal , Galinhas , Osteogênese , Osteoprotegerina , Proantocianidinas , Ligante RANK , Animais , Osteoprotegerina/metabolismo , Osteoprotegerina/genética , Ligante RANK/metabolismo , Proantocianidinas/farmacologia , Proantocianidinas/administração & dosagem , Galinhas/crescimento & desenvolvimento , Osteogênese/efeitos dos fármacos , Embrião de Galinha , Ração Animal/análise , Osteoclastos/efeitos dos fármacos , Dieta/veterinária , Distribuição Aleatória , Suplementos Nutricionais/análise , Proteínas Aviárias/metabolismo , Proteínas Aviárias/genética , Relação Dose-Resposta a Droga
15.
Foods ; 13(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38672890

RESUMO

Zearalenone (ZEA), a mycotoxin widely present in crops and food, poses a major threat to animal and human health. The consumption of ZEA-contaminated food or feed causes intestinal damage. Therefore, exploring how to mitigate the intestinal damage caused by its ZEA is becoming increasingly important. Resveratrol (RSV), a polyphenol compound, mainly exists in Vitis vinifera, Polygonum cuspidatum, Arachis hypogaea, and other plants. It has potent anti-inflammatory and antioxidant activity. The primary objective of this study was to assess the defensive effects of RSV and its molecular mechanism on the intestinal mucosal injury induced by ZEA exposure in mice. The results showed that RSV pretreatment significantly reduced serum DAO and that D-lactate levels altered intestinal morphology and markedly restored TJ protein levels, intestinal goblet cell number, and MUC-2 gene expression after ZEA challenge. In addition, RSV significantly reversed serum pro-inflammatory factor levels and abnormal changes in intestinal MDA, CAT, and T-SOD. Additional research demonstrated that RSV decreased inflammation by blocking the translocation of nuclear factor-kappaB (NF-κB) p65 and decreased oxidative stress by activating the nuclear factor E2-related factor 2 (Nrf2) pathway and its associated antioxidant genes, including NQO1, γ-GCS, and GSH-PX. In summary, RSV supplementation attenuates intestinal oxidative stress, inflammation, and intestinal barrier dysfunction induced by ZEA exposure by mediating the NF-κB and Nrf2/HO-1 pathways.

16.
Sci Total Environ ; 929: 172392, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38608885

RESUMO

Cadmium (Cd) is a widely distributed environmental pollutant, primarily causing nephrotoxicity through renal proximal tubular cell impairment. Pyroptosis is an inflammation-related nucleotide-binding oligomerization segment-like receptor family 3 (NLRP3)-dependent pathway for programmed cell death. We previously reported that inappropriate inflammation caused by Cd is a major contributor to kidney injury. Therefore, research on Cd-induced inflammatory response and pyroptosis may clarify the mechanisms underlying Cd-induced nephrotoxicity. In this study, we observed that Cd-induced nephrotoxicity is associated with NLRP3 inflammasome activation, leading to an increase in proinflammatory cytokine expression and secretion, as well as pyroptosis-related gene upregulation, both in primary rat proximal tubular (rPT) cells and kidney tissue from Cd-treated rats. In vitro, these effects were significantly abrogated through siRNA-based Nlrp3 silencing; thus, Cd may trigger pyroptosis through an NLRP3 inflammasome-dependent pathway. Moreover, Cd exposure considerably elevated reactive oxygen species (ROS) content. N-acetyl-l-cysteine, an ROS scavenger, mitigated Cd-induced NLRP3 inflammasome activation and subsequent pyroptosis. Mechanistically, Cd hindered the expression and deacetylase activity of SIRT1, eventually leading to a decline in SIRT1-p65 interactions, followed by an elevation in acetylated p65 levels. The administration of resveratrol (a SIRT1 agonist) or overexpression of Sirt1 counteracted Cd-induced RELA/p65/NLRP3 pathway activation considerably, leading to pyroptosis. This is the first study to reveal significant contributions of SIRT1-triggered p65 deacetylation to pyroptosis and its protective effects against Cd-induced chronic kidney injury. Our results may aid in developing potential therapeutic strategies for preventing Cd-induced pyroptosis through SIRT1-mediated p65 deacetylation.


Assuntos
Cádmio , Células Epiteliais , Piroptose , Sirtuína 1 , Animais , Sirtuína 1/metabolismo , Piroptose/efeitos dos fármacos , Cádmio/toxicidade , Ratos , Células Epiteliais/efeitos dos fármacos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Túbulos Renais , Fator de Transcrição RelA/metabolismo , Acetilação , Inflamassomos/metabolismo , Túbulos Renais Proximais
17.
Sci Rep ; 14(1): 8998, 2024 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637546

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is considered the third leading cause of cancer mortality in the western world, offering advanced stage patients with few viable treatment options. Consequently, there remains an urgent unmet need to develop novel therapeutic strategies that can effectively inhibit pro-oncogenic molecular targets underpinning PDACs pathogenesis and progression. One such target is c-RAF, a downstream effector of RAS that is considered essential for the oncogenic growth and survival of mutant RAS-driven cancers (including KRASMT PDAC). Herein, we demonstrate how a novel cell-penetrating peptide disruptor (DRx-170) of the c-RAF-PDE8A protein-protein interaction (PPI) represents a differentiated approach to exploiting the c-RAF-cAMP/PKA signaling axes and treating KRAS-c-RAF dependent PDAC. Through disrupting the c-RAF-PDE8A protein complex, DRx-170 promotes the inactivation of c-RAF through an allosteric mechanism, dependent upon inactivating PKA phosphorylation. DRx-170 inhibits cell proliferation, adhesion and migration of a KRASMT PDAC cell line (PANC1), independent of ERK1/2 activity. Moreover, combining DRx-170 with afatinib significantly enhances PANC1 growth inhibition in both 2D and 3D cellular models. DRx-170 sensitivity appears to correlate with c-RAF dependency. This proof-of-concept study supports the development of DRx-170 as a novel and differentiated strategy for targeting c-RAF activity in KRAS-c-RAF dependent PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Transdução de Sinais , Proliferação de Células , Linhagem Celular Tumoral , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo
18.
Ying Yong Sheng Tai Xue Bao ; 35(3): 713-720, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38646759

RESUMO

The problem of soil barrier caused by excessive accumulation of nitrogen is common in continuous cropping soil of facility agriculture. To investigate the modulating effects of biochar amendment on soil nitrogen transformation in greenhouse continuous cropping systems, we conducted a pot experiment with two treatments, no biochar addition (CK) and 5% biochar addition (mass ratio). We analyzed the effects of biochar addition on soil microbial community structure, abundances of genes functioning in nitrogen cycling, root growth and nitrogen metabolism-related genes expressions of cucumber seedlings. The results showed that biochar addition significantly increased plant height, root dry mass, total root length, root surface area, and root volume of cucumber seedlings. Rhizosphere environment was improved, which enhanced root nitrogen absorption by inducing the up-regulation of genes expressions related to plant nitrogen metabolism. Biochar addition significantly increased soil microbial biomass nitrogen, nitrate nitrogen, and nitrite nitrogen contents. The abundances of bacteria that involved in nitrogen metabolism, including Proteobacteria, Cyanobacteria, and Rhizobiales (soil nitrogen-fixing bacteria), were also significantly improved in the soil. The abundances of genes functioning in soil nitrification and nitrogen assimilation reduction, and the activities of enzymes involved in nitrogen metabolisms such as hydroxylamine dehydrogenase, nitronate monooxygenase, carbonic anhydrase were increased. In summary, biochar addition improved soil physicochemical properties and microbial community, and affected soil nitrogen cycling through promoting nitrification and nitrogen assimilation. Finally, nitrogen adsorption capacity and growth of cucumber plant was increased.


Assuntos
Carvão Vegetal , Cucumis sativus , Nitrogênio , Raízes de Plantas , Plântula , Solo , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/metabolismo , Nitrogênio/metabolismo , Solo/química , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Microbiologia do Solo , Agricultura/métodos , Rizosfera
19.
Opt Express ; 32(4): 5362-5379, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439265

RESUMO

The light field (LF) imaging systems face a trade-off between the spatial and angular resolution in a limited sensor resolution. Various networks have been proposed to enhance the spatial resolution of the sub-aperture image (SAI). However, the spatial shift-variant characteristics of the LF are not considered, and few efforts have been made to recover a full-resolution (FR) image. In this paper, we propose an FR image restoration method by embedding LF degradation kernels into the network. An explicit convolution model based on the scalar diffraction theory is first derived to calculate the system response and imaging matrix. Based on the analysis of LF image formation, we establish the mapping from an FR image to the SAI through the SAI kernel, which is a spatial shift-variant degradation (SSVD) kernel. Then, the SSVD kernels are embedded into the proposed network as prior knowledge. An SSVD convolution layer is specially designed to handle the view-wise degradation feature and speed up the training process. A refinement block is designed to preserve the entire image details. Moreover, our network is evaluated on extensive simulated and real-world LF images to demonstrate its superior performance compared with other methods. Experiments on a multi-focus scene further prove that our network is suitable for any in-focus or defocused conditions.

20.
Bioresour Technol ; 399: 130629, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552858

RESUMO

The pilot-scale simultaneous denitrification and methanation (SDM)-partial nitrification (PN)-anaerobic ammonia oxidation (Anammox) system was designed to treat anaerobic digestion effluent of kitchen waste (ADE-KW). The SDM-PN was first started to avoid the inhibition of high-concentration pollutants. Subsequently, Anammox was coupled to realize autotrophic nitrogen removal. Shortcut nitrification-denitrification achieved by the SDM-PN. The NO2--N accumulation (92 %) and NH4+-N conversion (60 %) were achieved by PN, and the removal of TN and COD from the SDM-PN was 70 % and 73 %, respectively. After coupling Anammox, the TN (95 %) was removed with a TN removal rate of 0.51 kg·m-3·d-1. Microbiological analyses showed a shift from dominance by Methanothermobacter to co-dominance by Methanothermobacter, Thermomonas, and Flavobacterium in SDM during the SDM-PN. While after coupling Anammox, Candidatus kuenenia was enriched in the Anammox zone, the SDM zone shifted back to being dominated by Methanothermobacter. Overall, this study provides new ideas for the treatment of ADE-KW.


Assuntos
Oxidação Anaeróbia da Amônia , Desnitrificação , Nitrogênio , Anaerobiose , Oxirredução , Reatores Biológicos/microbiologia , Nitrificação , Esgotos
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