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1.
Ecotoxicol Environ Saf ; 284: 117004, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39270416

RESUMO

With the increase of cadmium content in the environment, the losses caused by cadmium-induced intestinal diseases to animal husbandry are increasing year by year. However, most of the on-going research activities focus on zoonotic diseases rather than exploring the mechanisms of animal disease occurrence from an anthropogenic environmental perspective. In this study, stressed Hu sheep under cadmium environmental exposure were selected to explore the mechanism of inflammatory bowel disease development. 16 s, untargeted metabolomics and transcriptomic multiomics were used to analyze the changes of their intestinal tract and intestinal contents. The results showed that the beneficial microorganisms (s_Ruminococcus_sp) in the Cd group were significantly decreased and the potentially harmful microorganisms were significantly enriched, and the changes of these microorganisms affected the changes of metabolites (caprylic acid) to a certain extent, resulting in a decrease in fatty acids in the intestine. Due to the combined effect of cadmium ion and fatty acid reduction, the PPAR signaling pathway was inhibited, and the fatty acid transport and binding were further reduced, causing very serious damage to the intestine. We revealed for the first time the mechanism of intestinal injury in Hu sheeps under cadmium environmental exposure and provided new prevention and treatment methods of intestinal diseases under the environmental exposure to trace metals.


Assuntos
Cádmio , Colo , Intestino Delgado , Receptores Ativados por Proliferador de Peroxissomo , Transdução de Sinais , Animais , Cádmio/toxicidade , Transdução de Sinais/efeitos dos fármacos , Ovinos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Inflamação/induzido quimicamente , Exposição Ambiental/efeitos adversos , Doenças dos Ovinos/induzido quimicamente , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos
2.
Front Immunol ; 15: 1423775, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39192984

RESUMO

Background: Tertiary lymphoid structures (TLS), ordered structure of tumor-infiltrating immune cells in tumor immune microenvironment (TIME), play an important role in the development and anti-tumor immunity of various cancers, including liver, colon, and gastric cancers. Previous studies have demonstrated that the presence of TLS in intra-tumoral (IT), invasive margin (IM), and peri-tumoral (PT) regions of the tumors at various maturity statuses. However, the density of TLS in different regions of non-small cell lung cancer (NSCLC) has not been extensively studied. Methods: TLS and tumor-infiltrating immune cells were assessed using immunohistochemistry (IHC) staining in 82 NSCLC patients. Tumor samples were divided into three subregions as IT, IM and PT regions, and TLS were identified as early/primary TLS (E-TLS) or secondary/follicular TLS (F-TLS). The distribution of TLS in different maturity statuses, along with their correlation with clinicopathological characteristics and prognostic value, was assessed. Nomograms were used to predict the probability of 1-, 3-, and 5-year overall survival (OS) in patients with NSCLC. Results: The density of TLS and proportion of F-TLS in the IT region (90.2%, 0.45/mm2, and 61.0%, respectively) were significantly higher than those in the IM region (72.0%, 0.18/mm2, and 39.0%, respectively) and PT region (67.1%, 0.16/mm2, and 40.2%, respectively). A lower density of TLS, especially E-TLS in the IM region, was correlated with better prognosis in NSCLC patients. CD20+ B cells, CD3+ T cells, CD8+ cytotoxic T cells, and CD68+ macrophages were significantly overexpressed in the IM region. CD20+ B cells and CD3+ T cells in the IM region were significantly correlated with the density of E-TLS, while no statistically significant correlation was found with F-TLS. The E-TLS density in the IM region and TNM stage were independent prognostic factors for NSCLC patients. The nomogram showed good prognostic ability. Conclusions: A higher density of E-TLS in the IM region was associated with a worse prognosis in NSCLC patients, potentially due to the inhibition of TLS maturation caused by the increased density of suppressive immune cells at the tumor invasion front.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfócitos do Interstício Tumoral , Estruturas Linfoides Terciárias , Microambiente Tumoral , Humanos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estruturas Linfoides Terciárias/imunologia , Estruturas Linfoides Terciárias/patologia , Masculino , Feminino , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Prognóstico , Idoso , Microambiente Tumoral/imunologia , Linfócitos do Interstício Tumoral/imunologia , Adulto
3.
Mol Neurobiol ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963532

RESUMO

The comorbidity of anxiety and depression frequently occurs in patients with neuropathic pain. The ventrolateral orbital cortex (VLO) plays a critical role in mediating neuropathic pain and anxiodepression in rodents. Previous studies suggested that 5-HT6 receptors in the VLO are involved in neuropathic pain. Strong evidence supports a close link between 5-HT6 receptors and affective disorders such as depression and anxiety disorders. However, it remains unclear whether the 5-HT6 receptors in the VLO are involved in neuropathic pain-induced anxiodepression. Using a rat neuropathic pain model of spared nerve injury (SNI), we demonstrated that rats exhibited significant anxiodepression-like behaviors and the expression of VLO 5-HT6 receptors obviously decreased four weeks after SNI surgery. Microinjection of the 5-HT6 receptor agonist EMD-386088 into the VLO or overexpression of VLO 5-HT6 receptors alleviated anxiodepression-like behaviors. These effects were blocked by pre-microinjection of a selective 5-HT6 receptor antagonist (SB-258585) or inhibitors of AC (SQ-22536), PKA (H89), and MEK1/2 (U0126) respectively. Meanwhile, the expression of p-ERK, p-CREB, and BDNF in the VLO decreased four weeks after SNI surgery. Furthermore, administration of EMD-386088 upregulated the expression of BDNF, p-ERK, and p-CREB in the VLO of SNI rats, which were reversed by pre-injection of SB-258585. These findings suggest that activating 5-HT6 receptors in the VLO has anti-anxiodepressive effects in rats with neuropathic pain via activating AC-cAMP-PKA-MERK-CREB-BDNF signaling pathway. Accordingly, 5-HT6 receptor in the VLO could be a potential target for the treatment of the comorbidity of neuropathic pain and anxiodepression.

4.
Transl Cancer Res ; 13(4): 2043-2063, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38737692

RESUMO

Background and Objective: With advances in gut microbiome research, it has been recognized that the gut microbiome has an important and far-reaching impact on many human diseases, including cancer. Therefore, more and more researchers are focusing on the treatment of gut flora in tumors. In this article, we present a review of the mechanisms of gut microbes in tumor immunotherapy and related studies to provide reference for further research and insights into the clinical application of gut microbes. Methods: Between April 25, 2023, and November 25, 2023, we searched for articles published only in English between 1984 and 2023 using the databases PubMed, American Medical Association and Elsevier ScienceDirect using the keywords "gut microbiology" and "tumor" or "immunotherapy". Key Content and Findings: The gastrointestinal tract contains the largest number of microorganisms in the human body. Microorganisms are involved in regulating many physiological activities of the body. Studies have shown that gut microbes and their derivatives are involved in the occurrence and development of a variety of inflammations and tumors, and changes in their abundance and proportion affect the degree of cancer progression and sensitivity to immunotherapy. Gut microbiota-based drug research is ongoing, and some anti-tumor studies have entered the clinical trial stage. Conclusions: The abundance and proportion of intestinal microorganisms influence the susceptibility of tumors to tumor immunotherapy. This article reviewed the effects and mechanisms of gut microbes on tumor immunotherapy to further explore the medical value of gut microbes in tumor immunotherapy.

5.
Genomics ; 116(1): 110762, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38104669

RESUMO

Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted. We conducted a comprehensive analysis of the role of FANCD2 in cancer using public databases and other published studies. Moreover, we evaluated the role of FANCD2 in the proliferation, migration and invasion of lung adenocarcinoma cells through in vitro and in vivo experiments, and explored the role of FANCD2 in cisplatin chemoresistance. We investigated the regulatory effect of FANCD2 on the cell cycle of lung adenocarcinoma cells by flow cytometry, and verified this effect by western blotting. FANCD2 expression is elevated in most TCGA tumors and shows a strong positive correlation with poor prognosis in tumor patients. In addition, FANCD2 expression shows strong correlations with immune infiltration, immune checkpoints, the tumor mutation burden (TMB), and microsatellite instability (MSI), which are immune-related features, suggesting that it may be a potential target of tumor immunotherapy. We further found that FANCD2 significantly promotes the proliferation, invasion, and migration abilities of lung adenocarcinoma cells and that its ability to promote cancer cell proliferation may be achieved by modulating the cell cycle. The findings indicate that FANCD2 is a potential biomarker and therapeutic target in cancer treatment by analyzing the oncogenic role of FANCD2 in different tumors.


Assuntos
Carcinogênese , Proteína do Grupo de Complementação D2 da Anemia de Fanconi , Neoplasias , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Carcinogênese/genética , Dano ao DNA , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Neoplasias/genética , Neoplasias/patologia
6.
Cardiovasc Diabetol ; 22(1): 347, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102704

RESUMO

BACKGROUND: Previous studies have found that the triglyceride glucose index (TyG index) trajectories are associated with cardiovascular diseases. However, the association between the patterns of TyG index trajectories and risk for hypertension has not been investigated. In a longitudinal general population, we aimed to identify distinct TyG index trajectories over 12 years and describe their association with incidence of hypertension. METHOD: Of the 15,056 adults retrospectively recruited from the Physical Examination Center of the Second Affiliated Hospital of Dalian Medical University in northeast of China from 2011 to 2022. TyG index was calculated as ln (fasting TG [mg/dL] × FPG [mg/dL]/2) and the TyG index trajectories were developed using group-based trajectory modelling. Cox regression analysis was accomplished to assess the association between TyG index and incidence of hypertension. RESULTS: The median age of the population was 38 years, and 7352 (48.83%) of the participants were men. Three distinct TyG index trajectories were identified: "low increasing" (N = 7241), "moderate increasing" (N = 6448), and "high stable" (N = 1367). Using "low increasing" trajectory as a reference, "moderate increasing" and "high stable" trajectory were associated with increased risk of hypertension (HR = 2.45; 95% CI 2.25-2.67 and HR = 3.88; 95% CI 3.48-4.33). After adjusting for baseline sex, age, diabetes, smoking, systolic blood pressure, diastolic blood pressure, BMI, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, blood glucose, triglyceride, urea, uric acid, and glomerular filtration rate, the HR were slightly attenuate in "moderate increasing" and "high stable" trajectories to 1.38 (95% CI 1.23-1.54) and 1.69 (95% CI 1.40-2.02) respectively. Meanwhile, similar results were observed in multiple sensitivity analyses. The HR of the "moderate increasing" and "high stable" trajectory groups were 2.63 (95% CI 2.30-3.00) and 4.66 (95% CI 3.66-5.93) in female, and 1.66 (95% CI 1.48-1.86) and 2.33 (95% CI 2.04-2.66) in male. CONCLUSIONS: Elevated TyG index at baseline and long-term TyG index trajectories were associated with the risk of hypertension. Early identification of increasing TyG index could provide insights for preventing hypertension later in life.


Assuntos
Glucose , Hipertensão , Adulto , Humanos , Feminino , Masculino , Triglicerídeos , Estudos Retrospectivos , Estudos Longitudinais , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Glicemia , Fatores de Risco , Biomarcadores
7.
Polymers (Basel) ; 15(19)2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37836035

RESUMO

In recent years, all-inorganic cesium lead halide perovskite quantum dots have emerged as promising candidates for various optoelectronic applications, including sensors, light-emitting diodes, and solar cells, owing to their exceptional photoelectric properties. However, their commercial utilization has been limited by stability issues. In this study, we addressed this challenge by passivating the surface defects of CsPbBr3 quantum dots using indium acetate, a metal-organic compound. The resulting CsPbBr3 quantum dots exhibited not only high photoluminescence intensity, but also a remarkably narrow half-peak width of 19 nm. Furthermore, by embedding the CsPbBr3 quantum dots in ethylene-vinyl acetate, we achieved stretchability and significantly enhanced stability while preserving the original luminous intensity. The resulting composite film demonstrated the potential to improve the power conversion efficiency of crystalline silicon solar cells and enabled the creation of excellent white light-emitting diodes with coordinates of (0.33, 0.31). This co-passivation strategy, involving surface passivation and polymer packaging, provides a new idea for the practical application of CsPbBr3 quantum dots.

8.
J Orthop Surg Res ; 18(1): 629, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37635236

RESUMO

BACKGROUND: Neuropathic pain (NP) is the most prevalent form of chronic pain resulting from nerve damage or injury. Despite the widespread use of Duhuo Jisheng decoction (DHJSD) in traditional Chinese medicine (TCM) to treat chronic pain, the mechanism underlying its analgesic action remains unclear. METHODS: Using network pharmacology, we obtained DHJSD and NP-related target information from public databases to construct protein-protein interactions (PPI) and compound-target networks based on common target genes. These networks were further analyzed using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG). The interaction between molecules was verified through molecular docking using AutoDock Tools software. Additionally, we treated a chronic constriction injury (CCI) rat model with DHJSD and determined the mechanical withdrawal threshold (MWT). We used an enzyme-linked immunosorbent assay kit to determine the levels of inflammatory cytokines. Furthermore, qRT-PCR was employed to analyze ACHE, NOS2, MAPK3, PTGS2, AKT1, and PPARG mRNA expression, and immunofluorescence was used to evaluate changes in microglia. RESULTS: Our screening of compounds and targets identified 252 potential targets of DHJSD associated with NP. PPI analysis, along with GO and KEGG analyses, revealed that the potential mechanism of DHJSD in NP treatment may be related to inflammatory reactions, the IL-17 signaling pathway, MAP kinase activity, and endocrine activity. Based on molecular docking, the core target showed significant affinity for DHJSD's active components. Moreover, DHJSD treatment repaired the CCI-induced inflammatory reaction in the spinal cord while regulating the expression of ACHE, NOS2, MAPK3, PTGS2, AKT1, and PPARG mRNA. Immunofluorescence results indicated that the active components of DHJSD may regulate microglial M1 polarization to improve neuroinflammation, PPARG may have been involved in the process. CONCLUSION: The multi-component, multi-target, and multi-pathway actions of DHJSD provide new insights into its therapeutic mechanism in NP.


Assuntos
Dor Crônica , Neuralgia , Animais , Ratos , Doenças Neuroinflamatórias , Microglia , Ciclo-Oxigenase 2 , Simulação de Acoplamento Molecular , Farmacologia em Rede , PPAR gama , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Inflamação/tratamento farmacológico
9.
J Gastrointest Oncol ; 14(2): 1095-1113, 2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37201097

RESUMO

Background and Objective: As a surgical tool, indocyanine green (ICG) is increasingly used in surgery, especially in gastric and colorectal surgery. The use of ICG fluorescence imaging can improve the accuracy of tumor resection and potentially improve surgical outcomes for cancer patients. However, there are still different opinions or controversies on the application of ICG in the literature and the administration of ICG is still not uniform. In this review, we summarize the current status of its application and ICG administration methods in gastrointestinal cancer and discuss its existing limitations and future research directions. Methods: Literature published in the PubMed database from 1969 to 2022 was searched for using the keywords "Indocyanine green or near-infrared imaging or ICG", "gastric cancer", "gastroesophageal junction cancer", and "colorectal cancer" to summarize the main applications of ICG in gastrointestinal cancers. Key Content and Findings: ICG guidance can rapidly determine tumor location and save operative time, and can also visualize lymph nodes (LNs) in real-time, helping surgeons to retrieve more LNs for better postoperative staging, but its use in identifying sentinel lymph node (SLN) in gastric cancer (GC) remains controversial due to false negatives. ICG fluorescent angiography has great potential in preventing colorectal anastomotic leakage, but there is a dearth of high-caliber research evidence. In addition, ICG has unique advantages in detecting colorectal liver micrometastasis. Notably, there is still no uniform administration method and dose of ICG. Conclusions: In this review, we summarize the current status of ICG application in gastrointestinal cancer, and the current literature suggests that it is safe and effective and has the potential to change the clinical outcome of patients. Therefore, ICG should be routinely used in gastrointestinal cancers to improve the surgical outcomes of patients. In addition, this review summarizes the ICG administration in the literature, and we expect future guidelines to unitize and standardize the administration of ICG.

10.
ACS Omega ; 8(8): 7940-7949, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36873001

RESUMO

Foam drainage gas recovery technology is a chemical method to solve the serious bottom-hole liquid loading in the middle and late stages of gas well production, and the optimization of foam drainage agents (referred to as FDAs) is the key to the technology. According to the actual reservoir conditions, a high-temperature and high-pressure (HTHP) evaluation device for FDAs was set up in this study. The six key properties of FDAs, such as HTHP resistance, dynamic liquid carrying capacity, oil resistance, and salinity resistance, were evaluated systematically. Taking initial foaming volume, half-life, comprehensive index, and liquid carrying rate as evaluation indexes, the FDA with the best performance was selected and the concentration was optimized. In addition, the experimental results were verified by surface tension measurement and electron microscopy observation. The results showed that the sulfonate compound surfactant (UT-6) had good foamability, excellent foam stability, and better oil resistance at high temperature and high pressure. In addition, UT-6 had stronger liquid carrying capacity at a lower concentration, which could meet the production requirement when the salinity was 80 000 mg/L. Therefore, compared with the other five FDAs, UT-6 was more suitable for HTHP gas wells in block X of the Bohai Bay Basin, whose optimal concentration was 0.25 wt %. Interestingly, the UT-6 solution had the lowest surface tension at the same concentration, with the generated bubbles being closely arranged and uniform in size. Moreover, in the UT-6 foam system, the drainage speed at the plateau boundary was relatively slower with the smallest bubble. It is expected that UT-6 will become a promising candidate for foam drainage gas recovery technology in HTHP gas wells.

11.
Life (Basel) ; 12(11)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36431056

RESUMO

Waterlogging is a major threat to maize production worldwide. The exogenous application of spermidine is well known to enhance plant tolerance to abiotic stresses. The role of exogenous spermidine application in waterlogging tolerance in maize was investigated in this study. Two maize varieties (a waterlogging-tolerant variety: Xundan 20 (XD20) and a waterlogging-sensitive variety: Denghai 662 (DH662)) were subjected to waterlogging stress at the seedling stage, and then foliar spraying of 0.75 mM spermidine or purified water. Findings demonstrated lower chlorophyll content, reduced growth indices, considerable increase in superoxide anion (O2-) generation rate, and H2O2/malondialdehyde accumulation in the two maize varieties under waterlogging stress compared to the control treatment. However, the tolerance variety performed better than the sensitive one. Foliar application of spermidine significantly increased antioxidant enzyme activities under waterlogging stress. In addition, the application of spermidine increased polyamine levels and led to the reduction of ethylene levels under waterlogging. Consequences of spermidine application were most apparent for the waterlogging-sensitive cultivar DH662 under waterlogging than the waterlogging-tolerant variety XD20.

12.
Cell Death Discov ; 8(1): 306, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35790734

RESUMO

PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a "pseudokinase", contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear. This study demonstrated that TRIB2, not a "pseudokinase", has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. The elevated pSer37-PKM2 would subsequently promote the PKM2 dimers to enter into nucleus and increase the expression of LDHA, GLUT1, and PTBP1. The aerobic glycolysis is then elevated to promote cancer cell proliferation and migration in TRIB2- or PKM2-overexpressed cultures. The glucose uptake and lactate production increased, but the ATP content decreased in TRIB2- or PKM2-treated cultures. Experiments of TRIB2-/- mice further supported that TRIB2 could regulate aerobic glycolysis by PKM2. Thus, these results reveal the new kinase activity of TRIB2 and its mechanism in cancer metabolism may be related to regulating PKM2 to promote lung cancer cell proliferation in vitro and in vivo, suggesting promising therapeutic targets for cancer therapy by controlling cancer metabolism.

13.
Thorac Cancer ; 13(6): 832-843, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35076182

RESUMO

BACKGROUND: MicroRNAs (miRNAs) function as potential diagnostic biomarkers in various cancers. This study aimed to evaluate the roles of miR-205-5p in lung cancer progression and diagnosis. MATERIALS AND METHODS: MiR-205-5p was detected by quantitative real-time PCR. The effect of miR-205-5p on cell proliferation and metastasis was estimated by MTT and flow cytometry. The expression of TP53INP1 and related genes was analyzed by immunoblotting. The diagnostic value of miR-205-5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. RESULTS: The miR-205-5p was increased in lung cancer tissues. MiR-205-5p mimics were promoted but its inhibitor suppressed cell proliferation and metastasis compared with control treatment in vitro and in vivo. By regulating the 3' untranslated region, miR-205-5p could negatively regulate TP53INP1 expression, which further inhibited the expression of RB1 and P21, but increased that of cyclinD1. Moreover, the serum miR-205-5p levels of patients with lung cancer were significantly higher than those of normal controls, and they were correlated with patients' gender, drinking status, and clinical stage. The area under the ROC curve of serum miR-205-5p in the diagnosis of non-small-cell lung cancer was 0.8250, respectively. The finding supported its possession of high diagnostic efficiency for lung cancer. CONCLUSIONS: MiR-205-5p promoted lung cancer cell proliferation and metastasis by negatively regulating the novel target TP53INP1, which further affected the expression of P21, RB1, and cyclin D1. Serum miR-205-5p is a novel and valuable biomarker for lung cancer diagnosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Regiões 3' não Traduzidas , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo
14.
Front Neurosci ; 15: 733779, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34602973

RESUMO

Knee osteoarthritis (KOA) is a common and disabling condition characterized by attacks of pain around the joints, and it is a typical disease that develops chronic pain. Previous studies have proved that 5-HT1, 5-HT2, and 5-HT3 receptors in the spinal cord are involved in electroacupuncture (EA) analgesia. The 5-HT7 receptor plays antinociceptive role in the spinal cord. However, it is unclear whether the 5-HT7 receptor is involved in EA analgesia. The 5-HT7 receptor is a stimulatory G-protein (Gs)-coupled receptor that activates adenylyl cyclase (AC) to stimulate cyclic adenosine monophosphate (cAMP) formation, which in turn activates protein kinase A (PKA). In the present study, we found that EA significantly increased the tactile threshold and the expression of the 5-HT7 receptor in the dorsal spinal cord. Intrathecal injection of 5-HT7 receptor agonist AS-19 mimicked the analgesic effect of EA, while a selective 5-HT7 receptor antagonist reversed this effect. Moreover, intrathecal injection of AC and PKA antagonists prior to EA intervention prevented its anti-allodynic effect. In addition, GABAA receptor antagonist bicuculline administered (intrathecal, i.t.) prior to EA intervention blocked the EA effect on pain hypersensitivity. Our data suggest that the spinal 5-HT7 receptor activates GABAergic neurons through the Gs-cAMP-PKA pathway and participates in EA-mediated inhibition of chronic pain in a mouse model of KOA.

16.
J Exp Bot ; 72(2): 283-301, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-32936902

RESUMO

In plants, 3´,5´-cyclic adenosine monophosphate (cAMP) is an important second messenger with varied functions; however, only a few adenylyl cyclases (ACs) that synthesize cAMP have been identified. Moreover, the biological roles of ACs/cAMP in response to stress remain largely unclear. In this study, we used quantitative proteomics techniques to identify a maize heat-induced putative disease-resistance RPP13-like protein 3 (ZmRPP13-LK3), which has three conserved catalytic AC centres. The AC activity of ZmRPP13-LK3 was confirmed by in vitro enzyme activity analysis, in vivo RNAi experiments, and functional complementation in the E. coli cyaA mutant. ZmRPP13-LK3 is located in the mitochondria. The results of in vitro and in vivo experiments indicated that ZmRPP13-LK3 interacts with ZmABC2, a possible cAMP exporter. Under heat stress, the concentrations of ZmRPP13-LK3 and cAMP in the ABA-deficient mutant vp5 were significantly less than those in the wild-type, and treatment with ABA and an ABA inhibitor affected ZmRPP13-LK3 expression in the wild-type. Application of 8-Br-cAMP, a cAMP analogue, increased heat-induced expression of heat-shock proteins in wild-type plants and alleviated heat-activated oxidative stress. Taken together, our results indicate that ZmRPP13-LK3, a new AC, can catalyse ATP for the production of cAMP and may be involved in ABA-regulated heat resistance.


Assuntos
Ácido Abscísico , Adenilil Ciclases , Adenilil Ciclases/genética , Escherichia coli , Resposta ao Choque Térmico , Zea mays/genética
17.
Materials (Basel) ; 13(17)2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32899317

RESUMO

Chloride-induced steel corrosion is the most concerning issue for the durability of concrete structures. Concrete and steel samples were obtained from a 30-year-old reinforced concrete bridge. The chloride content was measured by a potentiometric titration method and the microstructure of concrete was obtained by scanning electron microscopy and mercury intrusion porosimetry. The rust phases of the steel were detected by X-ray diffraction and Raman analysis. It was found that the convection depth for chloride transport in cracked concrete was significantly larger than that in uncracked concrete. The concrete in a pier column facing upstream had greater porosity due to the water impact and calcium leaching. The coefficients of variability of chloride diffusivity of concrete for the bridge deck and the pier column were significantly different. Rust phases including lepidocrocite, goethite, akaganeite, magnetite, and maghemite were detected using Raman spectroscopy and X-ray diffraction. The major phases of steel rust in the atmospheric zone were lepidocrocite and goethite, while they were lepidocrocite and maghemite in the tidal zone. The results of this study would provide information concerning the chloride-induced steel corrosion under a marine environment in order to predict long-term behaviors of a reinforced concrete structure.

18.
Curr Pharm Des ; 26(22): 2657-2660, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32175833

RESUMO

In the era of precision medicine, establishing a patient-derived cell model is crucial, whether in vitro or in vivo. Compared to the traditional cell lines, patient-derived primary cells represent precise genetic features from specific patients, but poor proliferative activity of human primary cells restricts their popular application. Conditional reprogramming (CR) is a new cell culture technique to achieve rapid growth of patient-derived cells in vitro, making it possible to identify the individual difference and screen drugs sensitivity. In this review, we will summarize the application and limitation of CR in tumor and inflammatory-related diseases, indicating the prospect of this technique for preclinical research.


Assuntos
Reprogramação Celular , Neoplasias , Técnicas de Cultura de Células , Linhagem Celular , Proliferação de Células , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética
19.
Zhongguo Zhong Yao Za Zhi ; 43(18): 3639-3643, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30384526

RESUMO

The present study was conducted to investigate the rule of sex steroid hormones dynamic in the periodic development of Whitmania pigra gonad. The dynamic of sex steroid hormones in different age of Wh. pigra were detected by enzymolysis, extraction and UPLC-MS/MS. The results showed that the concentrations of estrone, estriol, testosterone and progesterone in the Wh. pigra showed M-type curve and peaked in 6-month-old Wh. pigra. The concentrations of above-mentioned four steroid hormones were the lowest in 9-month-old and then increased slightly. The another peaks of testosterone and progesterone were found in 2-month-old and the another peaks of estrone and estriol were obtained in 8-month-old. The concentrations of testosterone and progesterone are slightly higher than estriol during 1-month-old to 4-month-old, and thereafter strone and estriol showed higher concentration than testosterone and progesterone. In summary, the concentrations of four sex steroid hormones in Wh. pigra increased gradually with the maturation of gonads and decreased rapidly after the discharge period, which indicated that the ratio between estrogen, androgen and progesterone may be greatly related to the specificity of gonad development.


Assuntos
Hormônios Esteroides Gonadais/análise , Gônadas/química , Sanguessugas/química , Animais , Cromatografia Líquida , Estradiol , Progesterona , Espectrometria de Massas em Tandem , Testosterona
20.
Stereotact Funct Neurosurg ; 96(3): 142-150, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30032132

RESUMO

BACKGROUND: Moving from awake surgery under local anesthesia to asleep surgery under general anesthesia will require to precisely predict the outcome of deep brain stimulation. OBJECTIVE: To propose a data-driven prediction of both the therapeutic effect and side effects of the surgery. METHODS: The retrospective intraoperative data from 30 patients operated on in the subthalamic nucleus were used to train an artificial neural network to predict the deep brain stimulation outcome. A leave-one-out validation was undertaken to give a predictive performance that would reflect the performance of the predictive model in clinical practice. Three-dimensional coordinates and the amount of current of the electrodes were used to train the model. RESULTS: 130 electrode positions were reviewed. The areas under the curve were 0.902 and 0.89 for therapeutic and side effects, respectively. The mean sensitivity and specificity were 93.07% (SD 0.95) and 69.24% (SD 5.27) for the therapeutic effect, 73.47% (SD 10.55) and 91.82% (SD 0.12) for the side effect. CONCLUSION: Data-driven prediction could be an additional modality to predict deep brain stimulation outcome. Further validation is needed to precisely use this method for performing surgery under general anesthesia.


Assuntos
Estimulação Encefálica Profunda/métodos , Doença de Parkinson/terapia , Núcleo Subtalâmico/cirurgia , Adulto , Idoso , Eletrodos Implantados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vigília/fisiologia
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