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1.
J Cell Mol Med ; 26(5): 1579-1593, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35083859

RESUMO

Recent studies have shown that pyroptosis, an inflammatory form of cell death, has a dual role in tumorigenesis and tumour progression and affects the prognosis of patients; however, the role of pyroptosis in glioblastoma (GBM) is still unclear. In this study, based on GBM patients' data from two independent cohorts, we performed a comprehensive analysis of the expression and prognostic value of 33 pyroptosis-associated genes (PAGs) in GBM, as well as their role in the tumour immune microenvironment (TIME) of GBM. We identified 29 PAGs that were differentially expressed between GBM and normal brain tissue, 18 of which were upregulated in GBM tissue. Most of the 33 PAGs were strongly correlated with the levels of immune cell infiltration. Based on the 33 PAGs, the GBM samples can be divided into two clusters (C1-C2), with C1 having a 'hot' but immunosuppressive TIME and C2 having a 'cold' TIME, suggesting different immunotherapeutic responses in the two clusters. In addition, we identified four PAGs that were strongly associated with GBM prognosis and constructed a risk model based on these four PAGs. This risk model is an independent prognostic factor for GBM patients, and there is a different immune status between high- and low-risk groups. In conclusion, this study demonstrates that pyroptosis is closely associated with the prognosis and TIME of GBM and provides an important basis for further studies on the relationship between pyroptosis and GBM.


Assuntos
Glioblastoma , Glioblastoma/patologia , Humanos , Piroptose/genética , Microambiente Tumoral/genética
2.
Mol Reprod Dev ; 89(9): 413-422, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35853138

RESUMO

In this study, we investigated the mitochondrial energy supply capacity and molecular mechanisms of apoptosis, mitochondrial fission, and mitophagy in regulating mitochondrial degeneration in testis of striped dwarf hamsters (Cricetulus barabensis) under mild low temperature (15°C) and short daylight (10 h:14 h) conditions. Results showed that under moderate daylight and mild low temperature (ML), short daylight and moderate temperature (SM), short daylight and mild low temperature (SL) conditions, the mitochondria were swollen and cristae were disrupted. Compared with the moderate daylight & moderate temperature group (MM; 12 h:12 h, 22°C), the number of mitochondria was significantly decreased in the SM and SL groups. Both short daylight and mild low temperature reduced the protein expression of citrate synthase, thus the energy supply capacity of mitochondria may be weakened. Compared with the MM group, bax/bcl2 protein expression was higher in three treatment groups, and caspase3 activity increased in SM and SL groups, suggesting that short daylight can induce apoptosis. DRP1 protein expression showed no difference in four groups, while the FIS1 protein expression was significantly decreased in three treatment groups, this indicates that short daylight and mild low temperature can increase mitochondrial fission level. PINK1 protein expression was significantly increased in ML and SL groups, indicates that mild low temperature will lead to increased mitophagy level. Generally, short daylight induced degeneration of mitochondria in the testis of hamsters mainly by increasing apoptosis, while under mild low temperature, balanced regulation of mitophagy and mitochondrial fission appear to contribute to the protection of mitochondria.


Assuntos
Mitocôndrias , Testículo , Animais , Citrato (si)-Sintase/metabolismo , Citrato (si)-Sintase/farmacologia , Cricetinae , Cricetulus , Masculino , Mitocôndrias/metabolismo , Proteínas Quinases/metabolismo , Proteínas Quinases/farmacologia , Temperatura , Testículo/metabolismo , Proteína X Associada a bcl-2/metabolismo
3.
J Integr Neurosci ; 20(1): 77-85, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33834693

RESUMO

The social behavior mechanisms have not been thoroughly reported in the solitary female striped dwarf hamster (Cricetulus barabensis). In this study, the handling bag test and neutral arena measurements were used to detect the changes of aggression in the face of rivals of different genders of wild striped dwarf hamsters. We found that female hamsters had the highest aggressive performance in proestrus, followed by estrus, and the lowest in metestrus and the dioestrus, and the increased aggression during the proestrus or estrus period was low-intensity aggression such as intimidation, shock, boxing and counterattack, or even ritualized non-harmful behaviors to drive away opponents. When confronted with male individuals, aggression in females decreased significantly during estrus. The concentration of plasma estradiol was the highest in estrus and the lowest in metestrus and dioestrus. In contrast, estrogen receptor 2 relative expression in the hypothalamus is the lowest in proestrus and highest in metestrus and dioestrus. Besides, both estradiol levels in plasma and estrogen receptor 2 mRNA in the hypothalamus were associated with aggression. These results will broaden our understanding of the molecular mechanism of how breeding phenotype is an essential driver in changing the social behavior of female Cricetulus barabensis.


Assuntos
Agressão/fisiologia , Comportamento Animal/fisiologia , Estradiol/sangue , Receptor beta de Estrogênio/metabolismo , Ciclo Estral/fisiologia , Hipotálamo/metabolismo , Comportamento Social , Animais , Cricetinae , Ciclo Estral/metabolismo , Feminino , Masculino
4.
Molecules ; 26(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066584

RESUMO

The sensitive and selective detection of dopamine (DA) is very important for the early diagnosis of DA-related diseases. In this study, we reported the colorimetric detection of DA using Ganoderma lucidum polysaccharide (GLP) stabilized platinum nanoclusters (Ptn-GLP NCs). When Pt600-GLP NCs was added, 3,3',5,5'-tetramethylbenzidine (TMB) was rapidly catalyzed and oxidized to blue oxTMB, indicating the peroxidase-like activity of Pt600-GLP NCs. The catalytic reaction on the substrate TMB followed the Michaelis-Menton kinetics with the ping-pong mechanism. The mechanism of the colorimetric reaction was mainly due to the formation of hydroxyl radical (•OH). Furthermore, the catalytic reaction of Pt600-GLP NCs was used in the colorimetric detection of DA. The linear range for DA was 1-100 µM and the detection limit was 0.66 µM. The sensitive detection of DA using Pt-GLP NCs with peroxidase-like activity offers a simple and practical method that may have great potential applications in the biotechnology field.


Assuntos
Benzidinas/química , Dopamina/análise , Dopamina/sangue , Peroxidase/química , Polissacarídeos/química , Reishi/química , Encefalopatias/metabolismo , Catálise , Colorimetria , Humanos , Cinética , Limite de Detecção , Peso Molecular , Nanopartículas/química , Oxirredutases/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
5.
J Clin Lab Anal ; 34(12): e23542, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32860455

RESUMO

BACKGROUND: This study was to conduct a predictive model for the prognosis of aneurysmal subarachnoid hemorrhage (aSAH) and validate the clinical data. METHODS: A total of 235 aSAH patients were enrolled in this study, dividing into the favorable or poor prognosis groups based on Modified Rankin Scale (mRS) at 3 months postoperatively. Multivariate analysis was assessed using binary Logistic regression and Fisher discriminant analysis. The receiver operating characteristic (ROC) curve was used to determine the cut-off value. RESULTS: Our findings showed that the high Glasgow Coma Scale (GCS) score 24-hour after surgery reduced the risk of poor prognosis, and the surgical clipping and elevated neutrophil-lymphocyte ratio (NLR) increased the risk of poor prognosis. The discriminant function was V = 0.881 × GCS score - 0.523 × NLR - 0.422 × therapeutic approach, and V = -0.689 served as a cut-off value. When V ≥ -0.689, the good prognosis was considered among these patients with aSAH. The correctness for predicting the prognostic outcomes by self-validation was 85.11%. CONCLUSION: This predictive model established by a discriminant analysis is a useful tool for predicting the prognostic outcomes of aSAH patients, which may help clinicians identify patients at high risk for poor prognosis and optimize treatment after surgery.


Assuntos
Hemorragia Subaracnóidea , Idoso , Análise Discriminante , Feminino , Escala de Coma de Glasgow , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/mortalidade , Hemorragia Subaracnóidea/terapia
6.
Artigo em Inglês | MEDLINE | ID: mdl-32673738

RESUMO

Reduced ambient temperature has a damaging effect on mammalian myocardium. Huddling as a cooperative behavior has evolved in social mammals as a strategy to maximize adaptation to environmental cooling. Here, we studied the effects of huddling behavior on mitochondrial morphology, number, and function in the myocardia of Brandt's voles (Lasiopodomys brandtii) under cool environmental temperatures (15 °C). Results showed (1) mitochondrial swelling and cristae disruption in the cool huddling group (CH) and cool separated group (CS). Compared to the control group (CON, 22 °C), damaged mitochondria in the cool huddling and separated groups reached >90%; however, total number of mitochondria in the CH group was similar to that in the CON group. (2) ATP synthase activity was lowest in the CS group, whereas citrate synthetase activity was maintained among the three treatment groups. (3) Bax/bcl2 protein expression in the CH and CS groups was higher than that in the CON group, whereas DNA fragmentation, nuclear number, and caspase3 activity showed no significant differences among the three groups. (4) The protein expression levels of dynamin-related protein1 and mitochondrial fission factor were highest in the CH group. (5) Both protein expression of PINK1 and phosphorylation ratio of Parkin showed the pattern CS > CH > CON. (6) Total number of mitochondria was higher in males than in females. In general, the increased mitochondrial fission level observed in huddling voles partially counteracted the decrease in myocardial mitochondria caused by the increase in autophagy.


Assuntos
Arvicolinae/fisiologia , Temperatura Baixa , Mitocôndrias Cardíacas/ultraestrutura , Adaptação Fisiológica/fisiologia , Animais , Apoptose , Autofagia , Comportamento Animal , Peso Corporal , Caspase 3/metabolismo , Núcleo Celular/metabolismo , Feminino , Masculino , Mitocôndrias/metabolismo , Comportamento Social , Proteína X Associada a bcl-2/metabolismo
7.
Int J Syst Evol Microbiol ; 68(6): 1986-1991, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29683420

RESUMO

A Gram-stain-negative, rod-shaped, non-motile and halophilic bacterium, designated N53T, was isolated from a marine solar saltern in Wendeng, China. Cells of strain N53T were 0.3-0.4 µm wide and 2.0-5.5 µm long, catalase-positive and oxidase-positive. The bacterium grew optimally at 33 °C, at pH 7.0-8.0 and in the presence of 6.0 % (w/v) NaCl. Bacteriochlorophyll a was not found. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain N53T formed a phylogenetic lineage with members of the genus Roseovarius. Strain N53T exhibited the highest levels of similarity to Roseovarius pacificus (94.6 %) and Roseovarius confluentis (94.6 %), with a lower level to Roseovarius tolerans was 94.0 %. The percentage of conserved proteins and average nucleotide identity values between N53T and the type strain of the type species, Roseovarius tolerans, were 66.1 and 76.4 %, respectively. The genomic DNA G+C content was 68.1 mol%. The sole respiratory quinone was ubiquinone-10. The predominant cellular fatty acids (>10 %) were C18 : 1ω7c (54.0 %) and C16 : 0 (17.9 %). The polar lipids of strain N53T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, two unidentified phospholipids and two unidentified glycolipids. The differential phenotypic properties, together with the chemotaxonomic and genomic distinctiveness, revealed that strain N53T was separate from other recognized species of the genus Roseovarius. On the basis of the data presented here, strain N53T represents a novel species of the genus Roseovarius, for which the name Roseovariussalinarum sp. nov. is proposed. The type strain is N53T (=MCCC 1H00200T=KCTC 52886T).


Assuntos
Filogenia , Rhodobacteraceae/classificação , Salinidade , Microbiologia da Água , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Glicolipídeos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Rhodobacteraceae/genética , Rhodobacteraceae/isolamento & purificação , Análise de Sequência de DNA , Ubiquinona/química
8.
Int J Syst Evol Microbiol ; 68(11): 3523-3527, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30231957

RESUMO

A Gram-stain-negative, strictly aerobic, non-flagellated, rod-shaped bacterial strain, designated DC003T, was isolated from the alga Gracilariablodgettii of the phylum Rhodophyta collected from the coast of Lingshui county, Hainan, China. The strain grew optimally at 28 °C, pH 7.0-7.5 and in the presence of 2.0-3.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed strain DC003T to be within the genus Reichenbachiella, and most closely related to Reichenbachiella agariperforans JCM11238 (94.5 %), followed by Reichenbachiella faecimaris JCM 16588T (94.2 %). The major respiratory quinone was menaquinone 7 and the major fatty acids were iso-C15 : 0 and summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH). The polar lipids consisted of phosphatidylethanolamine, two unidentified aminophospholipids, three unidentified phospholipids and 10 unidentified lipids. The G+C content of the genomic DNA was 37.1 mol%. On the basis of the phenotypic, genotypic and phylogenetic analysis, strain DC003T is considered to represent a novel species of the genus Reichenbachiella, for which the name Reichenbachiellaversicolor sp. nov. is proposed. The type strain is DC003T (=KCTC 42867T=MCCC 1H00130T).


Assuntos
Cytophagaceae/classificação , Filogenia , Rodófitas/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Cytophagaceae/genética , Cytophagaceae/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
9.
Zhonghua Nan Ke Xue ; 23(8): 687-691, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-29726641

RESUMO

OBJECTIVE: To investigate the influence of deep slow-wave sleep deprivation on the oxidative stress of testicular tissue in rats. METHODS: Thirty-six 5-week-old male Wistar rats were equally randomized into deep slow-wave sleep deprivation group (SD1), deep slow-wave sleep and duration sleep deprivation group ( SD2), and a cage control group (CC). The rat model of deep slow-wave sleep deprivation was established using the flowerpot technique. The rats in the SD1 group were interfered every 24 minutes and deprived of 12 hours of sleep at night, those in the SD2 group deprived of 8 minutes of sleep at an interval of 24 minutes and 12 hours of sleep at night, and those in the CC group exposed to 12 hours of daylight and 12 hours of darkness. After 28 days, all the rats were executed for measurement of the testis volume and protein content, determination of the methane dicarboxylic aldehyde (MDA) level and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observation of the pathological changes in the testicular tissue under the microscope. RESULTS: Compared with the CC group, the rats in the SD1 and SD2 groups showed significantly reduced body weight (ï¼»268.5 ± 1.6ï¼½ vs ï¼»248.1 ± 25.1ï¼½andï¼»232.9 ± 10.1ï¼½g, P<0.05) and increased relative testis mass (ï¼»50.0 ± 1.3ï¼½ vs ï¼»57.9 ± 6.1ï¼½ and ï¼»54.9 ± 3.5ï¼½ ×10⁻², P<0.05). Statistically significant differences were found between the CC and SD2 groups in the contents of protein (ï¼»6.3 ± 1.4ï¼½ vs ï¼»4.5 ± 0.9ï¼½ gpro/L, P<0.05) and MDA (ï¼»1.1 ± 0.1ï¼½ vs ï¼»1.3 ± 0.3ï¼½ nmol/mgpro, P<0.05) and the activities of SOD (ï¼»104.3 ± 33.1ï¼½ vs ï¼»135.2 ± 26.9ï¼½ U/mgpro, P<0.05) and GSH-Px (ï¼»15.6 ± 4.0ï¼½ vs ï¼»21.7 ± 4.3ï¼½ U/mgpro, P<0.05), but not between the CC and SD1 groups (P>0.05). The lumens in the testis were narrowed, with obvious hyperplasia, hyperemia and edema in the peripheral interstitial tissue, but no significant pathologic changes were observed in the testis tissue of the SD1 group. CONCLUSIONS: Long-term deprivation of deep slow-wave sleep impairs the structure of the testis tissue and induces oxidative stress response in rats.


Assuntos
Estresse Oxidativo , Privação do Sono/metabolismo , Testículo/metabolismo , Testículo/patologia , Animais , Peso Corporal , Glutationa Peroxidase/análise , Masculino , Malondialdeído , Distribuição Aleatória , Ratos , Ratos Wistar , Fases do Sono , Superóxido Dismutase/análise , Fatores de Tempo , Redução de Peso
10.
Arch Anim Nutr ; 68(1): 1-15, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24422657

RESUMO

The present study was conducted to determine whether dietary threonine supplementation can improve immunity of weaned pigs challenged by swine Pseudorabies live vaccine (SPLV). Thirty crossbred piglets weaned at 21 days of age were randomly assigned to three groups receiving diets containing true ileal digestible threonine (TIDT) at 0.74, 0.89 and 1.11% for 14 days. On day 8, all pigs were injected intramuscularly with SPLV or sterile 0.9% NaCl solution. SPLV injection enhanced serum IgA, IgM, IgG, IFN-γ, IL-1ß, TNF-α and IL-10 concentrations (p < 0.05) and stimulated the relative mRNA abundance of Toll-like receptors (TLR3, TLR7 or TLR9) in different tissues (p < 0.05). Under no challenge, increasing dietary TIDT levels enhanced serum IgG (p < 0.05), IgM (p = 0.07) and IFN-γ (p < 0.05) concentration, tended to decrease serum IL-1ß, TNF-α and IL-10 concentration, and regulated relative mRNA abundance of TLR3, TLR7 or TLR9 in different tissues (p < 0.05). However, there was a synergistic role for increasing the serum IL-10 concentration between dietary TIDT levels and SPLV injection (p < 0.05). Under SPLV challenge, increasing dietary TIDT levels attenuated the increase of the serum IFN-γ concentration, and the increase of the relative mRNA abundance of TLR3, TLR7 and TLR9 in the different tissues (p < 0.05). These results suggest that an appropriate dietary threonine supplementation could improve the immune status of weaned pigs injected with SPLV by down-regulating the expression of TLR3, TLR7 and TLR9 in tissues, and thus regulating T-helper cytokine secretion.


Assuntos
Suplementos Nutricionais , Pseudorraiva/prevenção & controle , Doenças dos Suínos/prevenção & controle , Treonina/farmacologia , Vacinas Virais/imunologia , Ração Animal/análise , Animais , Dieta/veterinária , Ingestão de Alimentos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Imunoglobulinas/sangue , Masculino , RNA/metabolismo , Suínos , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Aumento de Peso
11.
Kaohsiung J Med Sci ; 39(7): 699-709, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37057810

RESUMO

The application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, has shifted lung cancer treatment from empirical chemotherapy to targeted molecular therapy. However, acquired drug resistance is inevitable in almost all non-small cell lung cancer (NSCLC) patients treated with gefitinib. Combined treatment with dihydroartemisinin (DHA) and gefitinib produced a better inhibitory effect on lung adenocarcinoma than gefitinib treatment alone; however, the specific mechanism remains unclear. In this study, we aimed to assess the underlying mechanism of this combination treatment. We prepared gefitinib-resistant A549 cells and investigated whether apoptosis and ferroptosis were involved in the sensitizing effect of DHA. Treatment with 5 µM gefitinib resulted in rupturing and floatation of A549 cells in the medium, while A549-GR cells were found to be insusceptible to gefitinib. However, treatment with DHA substantially inhibited the proliferation of A549-GR cells in a dose-dependent manner accompanied by increased apoptosis and ferroptosis. The accumulated reactive oxygen species (ROS) was crucial for the inhibitory effect of DHA on A549-GR cells. Moreover, cellular autophagy was significantly upregulated post-DHA treatment. The combined treatment of DHA and gefitinib resulted in inhibition of proliferation of A549, H1975, and HCC827 cells, and ROS accumulation and a remarkable induction of apoptosis was observed in A549-GR cells. DHA significantly induced apoptosis and ferroptosis in a dose-dependent manner and exhibited high cellular toxicity on A549-GR cells when combined with gefitinib.


Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Ferroptose , Neoplasias Pulmonares , Humanos , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Espécies Reativas de Oxigênio , Receptores ErbB/genética , Receptores ErbB/metabolismo , Quinazolinas/farmacologia , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Adenocarcinoma de Pulmão/tratamento farmacológico , Apoptose , Proliferação de Células , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
12.
Clin Respir J ; 17(9): 941-950, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37545476

RESUMO

BACKGROUND: We aimed to explore the prognostic differences among T1-4N0-2M0 non-small cell lung cancer (NSCLC) patients with bronchus involvements and to validate the T category of these patients in an external cohort. METHODS: Univariable and multivariable Cox analysis was performed to determine the prognostic factors. Kaplan-Meier method with a log-rank test was used to compare overall survival differences between groups. Propensity score matching method was used to minimize the bias caused by the imbalanced covariates between groups. RESULTS: A total of 169 390 eligible T1-4N0-2M0 NSCLC cases were included. There were 2354, 3367, 1638, 75, 87 585, 42 056, 19 246, and 13 069 cases in the group of superficial tumors of any size with invasive component limited to bronchial wall (T1-bronchus), tumors involving main stem bronchus ≥2 cm from carina (T2-main bronchus [≥2 cm]), tumors involving main stem bronchus <2 cm from carina (T2-main bronchus [<2 cm]), tumors with carina invasion (T4-carina), T1, T2, T3, and T4, respectively. Multivariable Cox analysis indicated that T1-bronchus patients had the best prognosis; T2-main bronchus (≥2 cm) and T2-main bronchus (<2 cm) patients had similar prognosis both in the entire cohort and in several subgroups. Survival curves showed that T1-bronchus and T1 patients had similar survival rates; the survivals of T2-main bronchus patients regardless of the distance from carina were comparable to those of T2 patients, and the survivals of T4-carina patients were also similar to those of T4 patients. CONCLUSIONS: Our results validated and supported the current T category for the patients with bronchus involvements, which might provide certain reference value for the revisions of T category in the next version of the tumor-node-metastasis stage classification.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Brônquios/patologia , Prognóstico , Taxa de Sobrevida , Estadiamento de Neoplasias , Estudos Retrospectivos
13.
Mater Today Bio ; 21: 100716, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37545557

RESUMO

Renal fibrosis is a pathological feature of chronic kidney disease and its progression correlates with kidney function impairment. Since there are currently no specific therapies for renal fibrosis, we explored whether inducing local production of the anti-fibrotic molecule relaxin-2 in kidney cells has potential as a strategy for suppressing the development of renal fibrosis. Our study examined whether delivery of relaxin-2 mRNA to kidney cells in vitro and in vivo could inhibit mechanisms leading to renal fibrosis. Transfecting relaxin-2 mRNA into cultured kidney cells inhibited fibrotic responses to TGF-ß1 in an autocrine or paracrine manner by reducing fibrotic gene expression in kidney tubules, and reducing proliferation in kidney fibroblasts and mesangial cells. Similarly, cubosomes assisted delivery of relaxin-2 mRNA to mouse kidneys alleviated the fibrosis and inflammation associated with renal injury following unilateral ureter obstruction (UUO). Therefore, relaxin-2 mRNA exhibits potential as a novel therapy for inhibiting fibrosis and inflammation in chronic kidney disease.

14.
Biosens Bioelectron ; 213: 114446, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35679650

RESUMO

The selective detection of glutathione (GSH) has been used as important colorimetric probe for human health. Herein, we used a facile method to synthesize manganese ions modified porphyrin metal-organic framework (PCN-224-Mn) with a size of 125.7 ± 14.2 nm and zeta potential of -3.9 ± 0.5 mV. We showed that PCN-224-Mn catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the absence of H2O2, resulting in a blue-colored oxidized TMB (oxTMB) that exhibits oxidase-like activity. Furthermore, a simple colorimetric detection method for GSH was developed based on the oxidase-like activity of PCN-224-Mn. This method shows wide linear detection range of 0.5-60 µM for GSH with a much lower detection limit of 0.233 µM. Finally, the recovery of colorimetric sensor of PCN-224-Mn suggests its great potential as a biosensor. As the catalytically active site, the manganese porphyrin unit plays a major role in the oxidase-like property and detection ability of PCN-224-Mn. Our data suggest that GSH detection method using PCN-224-Mn has great potential in multiple applications in the future.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Porfirinas , Humanos , Técnicas Biossensoriais/métodos , Colorimetria/métodos , Glutationa/química , Peróxido de Hidrogênio/química , Limite de Detecção , Manganês/química , Estruturas Metalorgânicas/química , Oxirredutases/química
15.
Viruses ; 14(10)2022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36298834

RESUMO

The nonstructural protein 1 (NS1) of influenza A virus (IAV) possesses multiple functions, such as the inhibition of the host antiviral immune responses, to facilitate viral infection. To search for cellular proteins interacting with the IAV NS1 protein, the yeast two-hybrid system was adopted. Proteasome family member PSMB4 (proteasome subunit beta type 4) was found to interact with the NS1 protein in this screening experiment. The binding domains of these two proteins were also determined using this system. The physical interactions between the NS1 and cellular PSMB4 proteins were further confirmed by co-immunoprecipitation assay and confocal microscopy in mammalian cells. Neither transiently nor stably expressed NS1 protein affected the PSMB4 expression in cells. In contrast, PSMB4 reduced the NS1 protein expression level, especially in the presence of MG132. As expected, the functions of the NS1 protein, such as inhibition of interferon activity and enhancement of transient gene expression, were suppressed by PSMB4. PSMB4 knockdown enhances IAV replication, while its overexpression attenuates IAV replication. Thus, the results of this study suggest that the cellular PSMB4 protein interacts with and possibly facilitates the degradation of the NS1 protein, which in turn suppresses IAV replication.


Assuntos
Vírus da Influenza A , Influenza Humana , Animais , Humanos , Replicação Viral , Complexo de Endopeptidases do Proteassoma/metabolismo , Interações Hospedeiro-Patógeno , Proteínas não Estruturais Virais/metabolismo , Interferons , Antivirais/metabolismo , Mamíferos
16.
Animals (Basel) ; 12(24)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36552491

RESUMO

The photoperiod regulates the seasonal reproduction of mammals by affecting the follicle development, for which the granulosa cells provide nutrition. However, the underlying mechanism remains unclear. Here, Djungarian hamsters (Phodopus sungorus) were raised under different photoperiods to study the ovarian status and explore the potential mechanism of the follicle development mediated by the FSH-Nodal/ALK7 signaling pathway. Compared with the moderate daylight (MD) group, the short daylight (SD) group exhibited a significant decrease in the ovarian weight and increase in the atretic follicle number and granulosa cell apoptosis, whereas the long daylight (LD) group showed an increase in the ovarian weight, the growing follicle number, and the antral follicle number, but a decrease in the granulosa cell apoptosis. Based on these findings, the key genes of the Nodal/ALK7 signaling pathway controlling the granulosa cell apoptosis were studied using the quantitative real-time polymerase chain reaction and western blotting. In the SD group, the follicle-stimulating hormone (FSH) concentration significantly decreased and the Nodal/ALK7/Smad signaling pathways were activated, while the phosphatidylinositol 3-kinase (PIK3)/Akt signaling pathway was inhibited. The BAX expression was significantly increased, while the Bcl-xL expression was significantly decreased, leading to an increase in the caspase-3 activity, the granulosa cell apoptosis, and ovarian degeneration. However, in the LD group, the FSH concentration significantly increased, the Nodal/ALK7/Smad signaling pathway was inhibited, and the PIK3/Akt signaling pathway was activated. Taken together, our results indicate that the photoperiod can regulate the apoptosis of the granulosa cells by regulating the concentration of FSH, activating or inhibiting the Nodal/ALK7 signaling pathway, thereby affecting the ovarian function. Our research provides an important theoretical basis for understanding the photoperiod-regulated mechanisms of the mammalian seasonal reproduction.

17.
Clin Endocrinol (Oxf) ; 74(2): 262-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21044115

RESUMO

OBJECTIVE: The importance of diagnosis and treatment of thyroid dysfunction during pregnancy has been widely recognized. We therefore established trimester- and method-specific reference intervals for thyroid testing in pregnant women according to the NACB recommended criteria. Several factors can affect the setting of reference intervals, in particular manufacturer's methodology, euthyroid definition and iodine status. DESIGN: Cross-sectional dataset analysis. SUBJECTS: Five hundred and five normal pregnant women at different stages of gestation were rigorously selected for setting reference intervals. All were healthy, iodine sufficient, euthyroid and negative for both serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). MEASUREMENTS: Thyrotrophin (TSH), total and free thyroxine (TT4 and FT4), total and free triiodothyronine (TT3 and FT3) and anti-TPOAb and anti-TgAb were measured using the Bayer ADVIA Centaur system. Iodine content in drinking water, salt and urine was determined by national standard methods. The 2·5th and 97·5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester. RESULTS: All participants had long-term consumption of iodized salt and median urinary iodine of 150-200 µg/l during each three trimester. The reference intervals for the first, second and third trimesters were, respectively, TSH 0·03-4·51, 0·05-4·50 and 0·47-4·54 mIU/l and FT4 11·8-21·0, 10·6-17·6 and 9·2-16·7 pmol/l. The manufacturer's method, euthyroid definition and iodine status may influence TSH and FT4 reference intervals. Alterations in thyroid hormone concentrations during pregnancy differed at different stage of gestation and to those of a nonpregnant state. CONCLUSIONS: The trimester- and method-based reference intervals for thyroid tests during pregnancy are clinically appropriate. Some variables should be controlled when establishing reference intervals.


Assuntos
Iodo/sangue , Glândula Tireoide/metabolismo , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Gravidez , Trimestres da Gravidez/sangue , Valores de Referência , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto Jovem
18.
Polymers (Basel) ; 13(11)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204167

RESUMO

Water soluble organic molecular pollution endangers human life and health. It becomes necessary to develop highly stable noble metal nanoparticles without aggregation in solution to improve their catalytic performance in treating pollution. Polyethyleneimine (PEI)-based stable micelles have the potential to stabilize noble metal nanoparticles due to the positive charge of PEI. In this study, we synthesized the amphiphilic PEI-oleic acid molecule by acylation reaction. Amphiphilic PEI-oleic acid assembled into stable PEI-oleic acid micelles with a hydrodynamic diameter of about 196 nm and a zeta potential of about 34 mV. The PEI-oleic acid micelles-stabilized palladium nanoparticles (PO-PdNPsn) were prepared by the reduction of sodium tetrachloropalladate using NaBH4 and the palladium nanoparticles (PdNPs) were anchored in the hydrophilic layer of the micelles. The prepared PO-PdNPsn had a small size for PdNPs and good stability in solution. Noteworthily, PO-PdNPs150 had the highest catalytic activity in reducing 4-nitrophenol (4-NP) (Knor = 18.53 s-1mM-1) and oxidizing morin (Knor = 143.57 s-1M-1) in aqueous solution than other previous catalysts. The enhanced property was attributed to the improving the stability of PdNPs by PEI-oleic acid micelles. The method described in this report has great potential to prepare many kinds of stable noble metal nanoparticles for treating aqueous pollution.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33340652

RESUMO

Harderian gland (HG) plays an important role in the physiological adaptation to terrestrial life, however, the mechanisms underlying the changes in the structure and function of the HG during aging remain unclear. This study investigated autophagy and apoptosis in the HG of striped dwarf hamsters (Cricetulus barabensis) of different ages (sub-adult, adult and aged groups) in both males and females. The results showed that LC3II/LC3I and puncta of LC3 were significantly higher in adult and aged individuals than sub-adults, whereas P62 decreased with age. Bax/bcl2was the highest in sub-adults of male and female individuals. Caspase3 activity was the highest in sub-adults of male and female individuals, and the citrate synthase activity was highest in sub-adults of females. ATP synthase, citrate synthase, dynamin-related protein 1 and mitochondrial fission factor (Mff) were the highest in sub-adults of females. Peptidylglycine α-amidating monooxygenase were the highest in the aged group, and those of gonadotropin-releasing hormone was the highest in the adult group. LC3II/LC3I, P62, Drp1, Fis, and bax/bcl2 were higher in males than that in females. These results suggest that apoptosis mainly affects growth and development in the HG, whereas autophagy affects aging. The difference of the HG weight and mitochondrial function between sexes is mainly related to the apoptosis.


Assuntos
Envelhecimento/metabolismo , Apoptose , Autofagia , Cricetulus/metabolismo , Glândula de Harder/citologia , Mitocôndrias/metabolismo , Animais , Caspase 3/metabolismo , Cricetulus/genética , Cricetulus/crescimento & desenvolvimento , Cricetulus/fisiologia , Fragmentação do DNA , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino
20.
Front Physiol ; 12: 593129, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841168

RESUMO

Small mammals exhibit limited glucose use and glycogen accumulation during hypothermia. Huddling is a highly evolved cooperative behavioral strategy in social mammals, allowing adaptation to environmental cooling. However, it is not clear whether this behavior affects the utilization of glycogen in cold environments. Here, we studied the effects of huddling on myocardial glycogen content in Brandt's voles (Lasiopodomys brandtii) under a mild cold environment (15°C). Results showed that (1) Compared to the control (22°C) group (CON), the number of glycogenosomes more than tripled in the cool separated group (CS) in both males and females; whereas the number of glycogenosomes increased in females but was maintained in males in the cool huddling group (CH). (2) Glycogen synthase (GS) activity in the CS group remained unchanged, whereas glycogen phosphorylase (GYPL) activity decreased, which mediated the accumulation of glycogen content of the CS group. (3) Both GS and GYPL activity increased which may contribute to the stability of glycogen content in CH group. (4) The expression levels of glucose transporters GLUT1 and GLUT4 increased in the CS group, accompanied by an increase in glucose metabolism. These results indicate that the reduced glycogen degradation enzyme level and enhanced glucose transport may lead to an increase in myocardial glycogen content of the separated voles under cool environment; while the up-regulation of glycogen synthesis and degradation enzyme level maintained myocardial glycogen content in the huddling vole.

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