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1.
Ann N Y Acad Sci ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38922711

RESUMO

This study aimed to investigate the protective effect of NAcM-OPT, a small molecule inhibitor of defective in cullin neddylation 1 (DCN1), on H2O2-induced oxidative damage in keratinocytes. Immortalized human keratinocytes (HaCaT cells) were treated with NAcM-OPT and exposed to oxidative stress. CCK-8 assays were used to measure cell viability. The mGFP-RFP-LC3 dual fluorescent autophagy indicator system was utilized to evaluate changes in autophagic flux. Western blotting was used to measure the expression of the autophagy-related proteins LC3 and Beclin 1. Keratinocytes were treated with the autophagy activator rapamycin, and HaCaT cell supernatant was added to PIG1 cells (immortalized human melanocytes), followed by evaluation of tyrosinase (TYR) expression via qRT-PCR. NAcM-OPT increased cell viability and cell proliferation. Furthermore, this molecule promoted autophagic flux through increased expression of autophagy-related proteins under H2O2-induced oxidative stress. Additionally, rapamycin increased the mRNA levels of TYR in PIG1 cells. Moreover, NAcM-OPT alleviated mitochondrial damage, restored mitochondrial function, and upregulated the expression of NFE2L2, HO1, NQO1, and GCLM. Importantly, NAcM-OPT also increased epidermal thickness, follicle length, and melanin synthesis under oxidative stress in vivo. These findings suggest that NAcM-OPT may be a promising small molecule antioxidant drug for the treatment of vitiligo.

2.
Inflamm Res ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839628

RESUMO

BACKGROUND: Regulatory T cells (Tregs) play vital roles in controlling immune reactions and maintaining immune tolerance in the body. The targeted destruction of epidermal melanocytes by activated CD8+T cells is a key event in the development of vitiligo. However, Tregs may exert immunosuppressive effects on CD8+T cells, which could be beneficial in treating vitiligo. METHODS: A comprehensive search of PubMed and Web of Science was conducted to gather information on Tregs and vitiligo. RESULTS: In vitiligo, there is a decrease in Treg numbers and impaired Treg functions, along with potential damage to Treg-related signaling pathways. Increasing Treg numbers and enhancing Treg function could lead to immunosuppressive effects on CD8+T cells. Recent research progress on Tregs in vitiligo has been summarized, highlighting various Treg-related therapies being investigated for clinical use. The current status of Treg-related therapeutic strategies and potential future directions for vitiligo treatment are also discussed. CONCLUSIONS: A deeper understanding of Tregs will be crucial for advancing Treg-related drug discovery and treatment development in vitiligo.

3.
Integr Zool ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597117

RESUMO

Golden snub-nosed monkeys show inconsistent frequency of placentophagy between wild and captive populations, with almost all births in the wild but around half of the births in captivity accompanied by the female's consumption of placenta. This aligns with nutritional demands-driven placentophagy, as captive populations are generally under less nutritional constraints for breeding females than the wild population. Placentophagy is probably adaptive in the wild and under positive selection due to nutritional benefits to both mothers and infants.

4.
BMC Oral Health ; 24(1): 50, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191414

RESUMO

BACKGROUND: The lateral profile is an important indicator of facial attractiveness. This study explored the general characteristics of the forehead profile and protrusion, and their relationship with related factors in structure and development. METHODS: Four hundred fourteen Chinese participants in the Yangtze River Delta region were involved. Including 206 males (17.15 ± 7.68 years old) and 208 females (18.35 ± 8.06 years old); 94 children (8.54 ± 2.21 years old, ranging from 4 to 12 years old), 166 adolescents (14.83 ± 1.50 years old, ranging from 13 to 17 years old), and 154 adults (25.52 ± 4.89, 18 years or older). The frontal section of the forehead was used to explore its shape. The straight distance between the vertical line of the FH plane through the nasal root point and its parallel line, which is tangential to the forehead, indicates the forehead prominence. Frontal sinus width was measured using the method described by Mahmood. RESULTS: The general shape of the forehead was straight and slightly bulged near the eyebrow arch in males but rounder in females. The average forehead protrusion in males was higher than that in females in adults. Significant differences in forehead protrusion between the dentoskeletal classifications and growth phases were notable. Frontal protrusion significantly correlated with frontal sinus depth, especially in males, adults, Class I, and those whose convex points were located in the lower section of the forehead. CONCLUSIONS: Age, race, and sex affect the forehead protrusion and frontal sinus width. Forehead protrusion may be an indicator of dentoskeletal deformities in the early stage. And dentoskeletal deformities may impair the correlation between the frontal sinuses and forehead protrusion during development. TRIAL REGISTRATION: This retrospective, cross-sectional study was reviewed and approved by the Research Ethical Committee (T2020008), and registered at ClinicalTrial.gov with an identified number (ChiCTR2100041913).


Assuntos
Testa , Má Oclusão , Adolescente , Adulto , Criança , Feminino , Masculino , Humanos , Adulto Jovem , Pré-Escolar , Estudos Transversais , Estudos Retrospectivos
5.
Biochem Genet ; 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38063952

RESUMO

Breast cancer is a common cancer worldwide. Hyperplastic enlarged lobular units (HELUs) are common changes in the breasts of adult women. HELUs may be closely related to the occurrence and development of breast cancer. In this study, genes that are commonly contained in the expression profiles of the genomes of the two diseases and have significant differences in expression before and after the respective diseases were identified. Various enrichment analyses were performed according to the expression levels of these differentially expressed genes. Furthermore, LASSO regression analysis was performed on the differentially expressed genes to identify genes significantly related to survival. The optimal risk model for the survival of patients with breast cancer was established, and the accuracy of the model was verified on multiple data sets. A gene combination containing 17 genes was ultimately determined to be an independent prognostic factor. Kaplan‒Meier survival analysis demonstrated the good performance of this risk model. The study found that Shared Gene Signatures and Biological Mechanisms in Hyperplastic Enlarged Lobular Units and Breast Cancer, screened 17 important Shared Gene Signatures of Hyperplastic Enlarged Lobular Units which are closely related to the survival of breast cancer patients through machine learning, and established a prognosis model with high-accuracy, which is worthy of further exploration.

6.
Cardiovasc Diabetol ; 22(1): 304, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940976

RESUMO

BACKGROUND: Triglyceride-glucose index (TyG) has been widely used to predict cardiovascular outcomes. However, it remains unclear whether TyG holds prognostic significance for patients with coronary chronic total occlusions (CTO). Thus, our study aimed to evaluate the predictive accuracy and prognostic value of TyG in individuals who underwent successful percutaneous coronary intervention (PCI) for CTO. METHODS: A total of 331 consecutive patients with ≥ 1 successful CTO-PCI were included. The baseline and angiographic data were acquired. The duration of follow-up ranged from 32 to 79 months, with a median of 44 months and an interquartile range of 39 to 67 months. The primary outcome measured was the occurrence of major adverse cardiac and cerebrovascular events (MACCE), including mortality, target vessel revascularization, recurrent myocardial infarction, and stroke. RESULTS: After controlling for confounders, multivariate Cox regression analysis revealed that TyG remained statistically significant, regardless of being a continuous or categorical variable. In the partially adjusted regression model, the Hazard ratio (95%CI) for MACCE was 2.54 (1.12-5.79) in tertile 3 and 1.61 (1.22-2.12) per SD increase in the TyG.Kaplan-Meier survival analysis demonstrated significant differences in MACCE-free survival rates across tertiles of the TyG, as indicated by the log-rank test (p = 0.001). ROC analysis was conducted to evaluate the predictive ability of TyG for MACCE, resulting in an AUC of 0.677. CONCLUSION: The TyG index demonstrates independent predictive capabilities for MACCE in patients who have undergone successful CTO-PCI. These findings suggest that TyG holds the potential as a valuable tool in risk stratification and the identification of patients who may benefit from early intervention in the management of CTO.


Assuntos
Oclusão Coronária , Intervenção Coronária Percutânea , Humanos , Fatores de Risco , Glucose , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Oclusão Coronária/etiologia , Triglicerídeos , Medição de Risco , Estudos Retrospectivos
7.
Front Microbiol ; 14: 1126189, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860485

RESUMO

Shift of ingestive behavior is an important strategy for animals to adapt to change of the environment. We knew that shifts in animal dietary habits lead to changes in the structure of the gut microbiota, but we are not sure about if changes in the composition and function of the gut microbiota respond to changes in the nutrient intake or food items. To investigate how animal feeding strategies affect nutrient intakes and thus alter the composition and digestion function of gut microbiota, we selected a group of wild primate group for the study. We quantified their diet and macronutrients intake in four seasons of a year, and instant fecal samples were analyzed by high-throughput sequencing of 16S rRNA and metagenomics. These results demonstrated that the main reason that causes seasonal shifts of gut microbiota is the macronutrient variation induced by seasonal dietary differences. Gut microbes can help to compensate for insufficient macronutrients intake of the host through microbial metabolic functions. This study contributes to a deeper understanding of the causes of seasonal variation in host-microbial variation in wild primates.

8.
BMC Bioinformatics ; 24(1): 110, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36959539

RESUMO

BACKGROUND: Drug‒drug interactions (DDIs) are reactions between two or more drugs, i.e., possible situations that occur when two or more drugs are used simultaneously. DDIs act as an important link in both drug development and clinical treatment. Since it is not possible to study the interactions of such a large number of drugs using experimental means, a computer-based deep learning solution is always worth investigating. We propose a deep learning-based model that uses twin convolutional neural networks to learn representations from multimodal drug data and to make predictions about the possible types of drug effects. RESULTS: In this paper, we propose a novel convolutional neural network algorithm using a Siamese network architecture called CNN-Siam. CNN-Siam uses a convolutional neural network (CNN) as a backbone network in the form of a twin network architecture to learn the feature representation of drug pairs from multimodal data of drugs (including chemical substructures, targets and enzymes). Moreover, this network is used to predict the types of drug interactions with the best optimization algorithms available (RAdam and LookAhead). The experimental data show that the CNN-Siam achieves an area under the precision-recall (AUPR) curve score of 0.96 on the benchmark dataset and a correct rate of 92%. These results are significant improvements compared to the state-of-the-art method (from 86 to 92%) and demonstrate the robustness of the CNN-Siam and the superiority of the new optimization algorithm through ablation experiments. CONCLUSION: The experimental results show that our multimodal siamese convolutional neural network can accurately predict DDIs, and the Siamese network architecture is able to learn the feature representation of drug pairs better than individual networks. CNN-Siam outperforms other state-of-the-art algorithms with the combination of data enhancement and better optimizers. But at the same time, CNN-Siam has some drawbacks, longer training time, generalization needs to be improved, and poorer classification results on some classes.


Assuntos
Aprendizado Profundo , Tailândia , Redes Neurais de Computação , Algoritmos , Interações Medicamentosas
9.
iScience ; 26(12): 108439, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38213790

RESUMO

Glycome in urine could be promising biomarkers for detecting pregnancy diagnosis and sex noninvasively for animals, especially for rare species. We explore the applicability of grouping golden snub-nosed monkeys by sex or diagnosing pregnancy based on their urinary glycopatterns, which are determined via lectin microarray combining mass spectrometry analysis. Sprague-Dawley rats are used to verify whether this approach and whether the glycomic biomarkers can be generalized to other mammalian species. The results show that, for both species, lectin microarray combining mass spectrometry can distinguish individuals' pregnancy status and sex; significant differences are found in the types, amounts, and terminal modification of glycans between pregnant and non-pregnant females and between females and males. This indicates the approach could be generalized to other mammalian species to group sex and detect pregnancy, yet the glycopatterns appear to be species-specific and markers developed from one species may not be directly applicable to another.

10.
Transbound Emerg Dis ; 69(6): 3724-3736, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36251176

RESUMO

Sarcoptic mange, a disease caused by the burrowing mite Sarcoptes scabiei, is globally endemic and an emerging threat to wildlife. Although many studies have shown that wildlife diseases play key roles in biodiversity conservation, knowledge about sarcoptic mange is still insufficient. In this study, we aim to improve the understanding of the impacts of sarcoptic mange on wildlife populations, the mechanisms involved in its eco-epidemiology and the associated risks to public and ecosystem health by investigating mass death events in gorals and serows in the Qinling Mountains. We conducted interviews with practitioners and local people in the central Qinling Mountains. From the same locations, we collected 24 cutaneous samples from various animals and surveillance data from infrared cameras. Pathological, parasitological and microbiological examinations of the samples were performed. Mite-induced cutaneous lesions, mites and eggs were observed in samples from dead gorals and one dead serow but not in other species. Molecular analysis confirmed the mites to be S. scabiei and shared the same cox 1 genotype. The data obtained from the interviews and infrared cameras indicated that the death of wildlife was related to sarcoptic mange infection and that there had been a decrease in the goral population since the outbreak of the disease. We confirmed that sarcoptic mange was the major cause of the mass death events and may have spread from the western to eastern Qinling Mountains. Based on our findings, we propose several protection strategies to help preserve biodiversity in the Qinling Mountains.


Assuntos
Escabiose , Animais , Escabiose/epidemiologia , Escabiose/veterinária , Ecossistema , Óvulo , Animais Selvagens , Biodiversidade , China/epidemiologia , Ruminantes
11.
Am J Orthod Dentofacial Orthop ; 162(5): e257-e266, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36089442

RESUMO

INTRODUCTION: Remodeling of the periodontal ligament (PDL) during orthodontic tooth movement is closely related to the vascularity of the PDL, which has not been thoroughly investigated in humans. This study aimed to measure the width and vascular parameters of human PDL using superb microvascular imaging for the first time. METHODS: Patients aged 18-25 years were selected for participation. The intervention was randomly allocated from the maxillary canines to the first molars on both sides using 50 g or 150 g of force. The width and vascular parameters of the PDL were measured using superb microvascular imaging at different time intervals (baseline, 30 minutes, and 1, 3, 7, and 14 days). RESULTS: Before the intervention, the width of the PDL ranged from 0.14 to 0.25 mm, and the vascular index ranged from 9.40% to 13.54%. After applying orthodontic forces, the cervical and middle PDL widths increased. The vascular index decreased slightly in 30 minutes, decreased to a minimum value after 1 day, increased to the maximum in 3-7 days, and returned to baseline values in 14 days. The values of other vascular parameters showed similar trends. CONCLUSIONS: The width and vascular parameters of the PDL changed slightly after force application, underwent changes in the period of reconstruction for 3-7 days, and eventually returned to baseline in 14 days.

12.
J Mol Neurosci ; 72(8): 1656-1669, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35596056

RESUMO

Our previous research found that activation of GPR55 can alleviate cognitive impairment induced by amyloid-beta 1-42 (Aß1-42) and streptozotocin in mice, but the role of GPR55 in the pathogenesis of cognitive impairment remains unknown. Here, we used a lipopolysaccharide (LPS) mouse model to further investigate the role and mechanism of O-1602, a GPR55 agonist, on cognitive dysfunction. ICR mice were treated with an intracerebroventricular (i.c.v.) injection of LPS, followed by cognitive function tests. The expression of GPR55, NF-κB p65, caspase-3, Bax, and Bcl-2 in the hippocampus was examined by Western blotting. Inflammatory cytokines and microglia were detected by ELISA kit and immunohistochemical analyses, respectively. The levels of MDA, GSH, SOD, and CAT were examined by assay kits. Furthermore, TUNEL-staining was used to detect neuronal apoptosis. Our results showed that i.c.v. injection of LPS in mice exhibited impaired performance in the behavior tests, which were ameliorated by O-1602 treatment (2.0 or 4.0 µg/mouse, i.c.v.). Importantly, we found that O-1602 treatment reversed GPR55 downregulation, decreased the expression of NF-κB p65, suppressed the accumulation of proinflammatory cytokines and microglia activation, increased the anti-inflammatory cytokines, and reduced the levels of MDA, increased the levels of GSH, SOD, and CAT in the hippocampus. In addition, O-1602 treatment also significantly reduced Bax and increased Bcl-2 expression as well as decreased caspase-3 activity and TUNEL-positive cells in the hippocampus. These observations indicate that O-1602 may ameliorate LPS-induced cognition deficits via inhibiting neuroinflammation, oxidative stress, and apoptosis mediated by the NF-κB pathway in mice.


Assuntos
Agonistas de Receptores de Canabinoides , Disfunção Cognitiva , Receptores de Canabinoides , Animais , Agonistas de Receptores de Canabinoides/farmacologia , Caspase 3/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Citocinas/metabolismo , Hipocampo/metabolismo , Lipopolissacarídeos/toxicidade , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos ICR , Microglia/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores de Canabinoides/metabolismo , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismo
13.
Pharmacol Biochem Behav ; 214: 173340, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35090841

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cascading changes in cognition and behavior. G-protein-coupled receptor 55 (GPR55) has been used as a promising target for the treatment of diabetes, but its function in AD is unclear. The objective of this study was to investigate the neuroprotective effects of O-1602, a GPR55 agonist, on the streptozotocin (STZ)-induced AD mouse model. A single intracerebroventricular (i.c.v.) injection of STZ into the brains of mice significantly induced cognitive impairment. In contrast, O-1602 (2.0 or 4.0 µg/mouse, i.c.v.) can improve the cognitive dysfunction caused by STZ in the Morris water maze (MWM) and novel object recognition (NOR) tests. Importantly, O-1602 treatment reversed STZ-induced GPR55 down-regulation, reduced the activity of ß-secretase 1 (BACE1) and the level of Aß1-42, and abolished the up-regulation of acetylcholinesterase (AChE) activity in the hippocampus and frontal cortex. Besides, O-1602 markedly suppressed STZ-induced oxidative stress, characterized by decreased malondialdehyde (MDA) level, and increased the levels of glutathione (GSH), superoxide dismutases (SOD), and catalase (CAT), as well as attenuated neuroinflammation as indicated by decreased series of pro-inflammatory cytokines and microglia activation. O-1602 treatment also ameliorated synaptic dysfunction by promoting the up-regulation of PSD-95 protein in the STZ-treated mice. Our results suggest that O-1602 has potent neuroprotective effects against STZ-induced neurotoxicity. Meanwhile, these findings suggest that GPR55 might be a novel and promising target for the treatment of AD.


Assuntos
Doença de Alzheimer , Canabidiol/análogos & derivados , Disfunção Cognitiva , Fármacos Neuroprotetores , Receptores de Canabinoides , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Canabidiol/farmacologia , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Aprendizagem em Labirinto , Camundongos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Receptores de Canabinoides/metabolismo , Estreptozocina/farmacologia , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Sinapses/patologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-34363866

RESUMO

The accumulation of amyloid-ß (Aß) peptides in the brain is considered to be the initial event in the Alzheimer's disease (AD). Neurotoxicity mediated by Aß has been demonstrated to damage the cognitive function. In the present study, we sought to determine the effects of O-1602, a specific G-protein coupled receptor 55 (GPR55) agonist, on the impairment of learning and memory induced by intracerebroventricular (i.c.v.) of Aß1-42 (400 pmol/mouse) in mice. Our results showed that i.c.v. injection of aggregated Aß1-42 into the brain of mice resulted in cognitive impairment and neurotoxicity. In contrast, O-1602 (2.0 or 4.0 µg/mouse, i.c.v.) can improve memory impairment induced by Aß1-42 in the Morris water maze (MWM), and novel object recognition (NOR) tests. Besides, we found that O-1602 reduced the activity of ß-secretase 1 (BACE1) and the level of soluble Aß1-42 in the hippocampus and frontal cortex. Importantly, O-1602 treatment reversed Aß1-42-induced GPR55 down-regulation, decreased pro-inflammatory cytokines, and the level of malondialdehyde (MDA), increased the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), as well as suppressed apoptosis as indicated by decreased TUNEL-positive cells, and increased the ratio of Bcl-2/Bax. O-1602 treatment also pronouncedly ameliorated synaptic dysfunction by promoting the upregulation of PSD-95 and synaptophysin (SYN) proteins. Moreover, O-1602 concurrently down regulated the protein levels of RhoA, and ROCK2, the critical proteins in the RhoA/ROCK2 pathway. This study indicates that O-1602 may reverse Aß1-42-induced cognitive impairment and neurotoxicity in mice by inhibiting RhoA/ROCK2 pathway. Taken together, these findings suggest that GPR55 could be a novel and promising target for the treatment of AD.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides , Canabidiol/análogos & derivados , Disfunção Cognitiva/tratamento farmacológico , Síndromes Neurotóxicas , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/efeitos adversos , Peptídeos beta-Amiloides/metabolismo , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Canabidiol/administração & dosagem , Modelos Animais de Doenças , Hipocampo/metabolismo , Infusões Intraventriculares , Transtornos da Memória/induzido quimicamente , Camundongos , Fragmentos de Peptídeos , Receptores de Canabinoides/genética
15.
Int Immunopharmacol ; 101(Pt B): 108335, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34781121

RESUMO

The accumulation of amyloid beta (Aß) in the brain is thought to be associated with cognitive deficits in Alzheimer's disease (AD). However, current methods to combat Aß neurotoxicity are still lacking. G protein-coupled receptor 17 (GPR17) has become a target for treating inflammation in brain diseases, but it is unclear whether it has a role in AD. Here, we investigated the effects of cangrelor, a GPR17 antagonist, on neurotoxicity and memory impairment induced by intracerebroventricular (i.c.v.) injection of Aß1-42 in mice. The behavior results showed that cangrelor (2.0 or 4.0 µg/mouse, i.c.v.) treatment reversed the deficits in memory and learning ability induced by Aß1-42 in mice. Importantly, we demonstrated for the first time that GPR17 expression in the hippocampus and frontal cortex is increased in response to Aß1-42 exposures. We also found that cangrelor treatment reduced the activity of ß-secretase 1 (BACE1) and the levels of soluble Aß1-42 in the hippocampus and frontal cortex. Meanwhile, cangrelor treatment suppressed oxidative stress induced by Aß1-42, as proved by reduced production of malondialdehyde (MDA), and increased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), and promoted the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Furthermore, cangrelor also suppressed Aß1-42-induced neuroinflammation, characterized by suppressed activation of microglia, decreased the levels of pro-inflammatory cytokines, and nuclear translocation of NF-κB p65, as well as ameliorated synaptic deficits by promoting the upregulation of synaptic proteins, and increasing the number of Golgi-Cox stained dendritic spines. These results suggest that cangrelor may reverse Aß1-42-induced cognition deficits via inhibiting oxidative stress, neuroinflammation, and synaptic dysfunction mediated by Nrf2/HO-1 and NF-κB signaling.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Sinapses Elétricas/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Fragmentos de Peptídeos/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Receptores Acoplados a Proteínas G/metabolismo , Monofosfato de Adenosina/uso terapêutico , Animais , Heme Oxigenase-1/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Transdução de Sinais
16.
Front Pharmacol ; 12: 719644, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483930

RESUMO

The cGAS-STING signaling pathway is an autoimmune inflammatory pathway that can trigger the expression of a series of inflammatory factors represented by type 1 interferon. Recent studies have found that the cGAS-STING signaling pathway played a significant role in liver physiology and was closely related to the progress of liver diseases. For example, activating the cGAS-STING signaling pathway could significantly inhibit hepatitis B virus (HBV) replication in vivo. Moreover, the cGAS-STING signaling pathway was also closely associated with tumor immunity in hepatocellular carcinoma (HCC). This review summarized the role of the cGAS-STING signaling pathway in several common liver diseases, especially the current application of the cGAS-STING signaling pathway in liver disease treatment, and prospected its future research, which provided a new idea for understanding and treating liver diseases.

17.
Bioact Mater ; 6(4): 916-927, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33210018

RESUMO

Copper is an indispensable trace metal element in the human body, which is mainly absorbed in the stomach and small intestine and excreted into the bile. Copper is an important component and catalytic agent of many enzymes and proteins in the body, so it can influence human health through multiple mechanisms. Based on the biological functions and benefits of copper, an increasing number of researchers in the field of biomaterials have focused on developing novel copper-containing biomaterials, which exhibit unique properties in protecting the cardiovascular system, promoting bone fracture healing, and exerting antibacterial effects. Copper can also be used in promoting incisional wounds healing, killing cancer cells, Positron Emission Tomography (PET) imaging, radioimmunological tracing and radiotherapy of cancer. In the present review, the biological functions of copper in the human body are presented, along with an overview of recent progress in our understanding of the biological applications and development of copper-containing materials. Furthermore, this review also provides the prospective on the challenges of those novel biomaterials for future clinical applications.

18.
PeerJ ; 7: e6214, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30697477

RESUMO

BACKGROUND: The red swamp crayfish, Procambarus clarkii (Girard, 1852), is one of the most promising freshwater species for aquaculture in China. Understanding its reproductive pattern and population dynamics is crucial for sustainable management, but there is currently a lack of fundamental knowledge of commercial P. clarkii populations. Therefore, the purpose of this study was to investigate the reproductive pattern and population dynamics of commercial P. clarkii throughout the yearly cycle. METHODS: A total of 2,051 crayfish (1,012 females and 1,039 males) were collected from March 2016 to February 2017 in the area of Selection and Reproduction Center of Crayfish. The reproductive pattern was evaluated by the gonadosomatic index (GSI), hepatosomatic index (HSI), ovarian development and fecundity. Growth, mortality rates and exploitation rate were estimated by electronic length frequency analysis by R package "TropFishR" based on data of cephalothorax length (CTL). RESULTS: Our results demonstrated that spawning activities of P. clarkii took place from September to November, with a mean fecundity of 429 ± 9 eggs per female. There were two recruitments yearly, a major one from October to November and a minor one from March to May. With respect to population growth, five growth cohorts were identified for both females and males. Crayfish grew faster but attained smaller asymptotic maximum CTL as indicated by higher growth coefficient (K), growth parameter index (Ø') and lower asymptotic CTL (Linf ). The estimates of total mortality rate (Z), natural mortality rate (M) and fishing mortality rate (F) were 1.93, 1.02, 0.91 year-1 for females and 2.32, 0.93, 1.39 year-1 for males, which showed that the mortality of male crayfish was mainly caused by fishing. The estimates of exploitation rate (E) indicated that male crayfish were overexploited, with the values of 0.47 and 0.60 year-1 for females and males, respectively. DISCUSSION: P. clarkii spawned from September to November while two recruitments were observed yearly. We inferred that some eggs, prevented from hatching by low water temperature in winter, were more likely to hatch in the next spring. Moreover, the fishing mortality rate was relatively high for males, which might be related to the males-directed selection during the reproductive period. The higher values of exploitation rate in our study confirmed that males P. clarkii were overexploited and were under high fishing pressure. We thus suggest reducing fishing intensity on immature crayfish and avoid sex selection during the reproductive period to improve the overall sustainability of commercial P. clarkii populations.

19.
Artigo em Inglês | MEDLINE | ID: mdl-29757963

RESUMO

This study aims to evaluate the acute toxicity of pymetrozine to juvenile Procambarus clarkii. Two 96-h toxicity tests were conducted to assess the lethal concentration 50 (LC50) values, behaviors, and histopathology (at 50% of the 96 h LC50) after pymetrozine exposure. The results showed high toxicity of pymetrozine to juvenile P. clarkii in a dose and time dependent manner, with a decreasing LC50 from 1.034 mg/L at 24 h to 0.479 mg/L at 96 h. The maximum allowable concentration (MAC) of pymetrozine for P. clarkii was 0.106 mg/L. Behavioral abnormalities were observed in pymetrozine-treated crayfish, such as incunabular hyperexcitability, subsequent disequilibrium, lethargy, and increased defecation. Significant lesions were observed in all pymetrozine-treated tissues, including: (1) in gill, hemocytic infiltration and 33.27% of epithelial cells lesions; (2) in perigastric organs, 64.37%, 29.06%, and 13.99% of tubules with lumen atrophy, vacuolation, and cell lysis, respectively; (3) in heart, 2.5%, 8.55% and 7.74% of hemocytic infiltration, vacuolization, and hyperplasia, respectively; (4) in stomach, 80.82%, 17.77%, 6.98%, 5.24% of cuticula swelling, vacuolization, muscle fragmentation, hemocytic infiltration, respectively; (5) in midgut, 7.45%, 10.98%, 6.74%, and 13.6% of hyperplasia, tissue lysis and vacuolation, hemocytic infiltration, muscle fracture; and (6) in abdominal muscle, 14.09% of myofiber fracture and lysis. This research demonstrates that pymetrozine is highly toxic to juvenile P. clarkii, with significant effects on mortality, behavior and histopathology at concentrations of ≤1.1 mg/L, while the estimated practical concentration of pymetrozine in rice-crayfish culture water was around 20 times lower than the calculated MAC.


Assuntos
Astacoidea/efeitos dos fármacos , Inseticidas/toxicidade , Triazinas/toxicidade , Animais , Aquicultura , Oryza , Testes de Toxicidade Aguda
20.
Artigo em Inglês | MEDLINE | ID: mdl-29186931

RESUMO

The mixture of bensulfuron-methyl and acetochlor (MBA) has been widely applied as a rice herbicide in China, but the mixture toxicity of MBA to aquatic organisms is largely unknown. The current study aims to investigate the acute effects of MBA to juvenile red swamp crayfish, Procambarus clarkii. Firstly, a 96 h semi-static exposure was conducted to determine the Lethal Concentration 50 (LC50) values at 24, 48, 72 and 96 h, as well as to assess the behavioral and morphological effects. A second 96 h exposure was conducted at an MBA concentration of 50% of the 96 h LC50 (72.62 mg/L) to assess the histological changes in the gill, perigastric organ, muscle, heart, stomach, and midgut. The results showed that MBA exhibited low acute toxicity with the 24, 48, 72 and 96 h LC50 values of 191.25 (179.37-215.75), 166.81 (159.49-176.55), 154.30 (148.36-160.59) and 145.24 (138.94-151.27) mg/L, respectively. MBA-exposed crayfish showed body jerk, belly arch, equilibrium loss, body and appendage sway, and lethargy; and the dead crayfish showed dark gray or grayish-white body color and separated cephalothorax and abdomen. At 72.62 mg/L, MBA exposure caused significant histopathological alterations, mainly including the cuticular and epithelial degeneration of all the gills; atrophy of tubule lumina and cellular vacuolation of the perigastric organs (61.15 ± 9.90% of the tubules showed lesions); epithelial hyperplasia (48.40 ± 9.00%), myocardial fibers and epithelial cell lysis (17.30 ± 2.01%), and hemocytic infiltration of the hearts; cuticular swelling (15.82 ± 2.98%) and vacuolate connective tissue (11.30 ± 2.47%) of the stomachs; atrophied bladder cell and fragmented longitudinal muscles (95.23 ± 4.77%) of the midguts; and slight myofibers fragmentation and lysis (7.37 ± 0.53%) of the abdominal muscles. Our results indicate that MBA can cause behavioral, morphological and histopathological effects on juvenile P. clarkii at relatively high concentrations, but its acute toxicity is low compared with many other common herbicides.


Assuntos
Astacoidea/efeitos dos fármacos , Herbicidas/toxicidade , Oryza , Compostos de Sulfonilureia/toxicidade , Toluidinas/toxicidade , Animais , China , Relação Dose-Resposta a Droga , Herbicidas/química , Compostos de Sulfonilureia/química , Fatores de Tempo , Toluidinas/química
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