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1.
Front Immunol ; 15: 1348391, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469312

RESUMO

Background: Rhinitis is a complex condition characterized by various subtypes, including allergic rhinitis (AR), which involves inflammatory reactions. The objective of this research was to identify crucial genes associated with inflammatory response that are relevant for the treatment and diagnosis of AR. Methods: We acquired the AR-related expression datasets (GSE75011 and GSE50223) from the Gene Expression Omnibus (GEO) database. In GSE75011, we compared the gene expression profiles between the HC and AR groups and identified differentially expressed genes (DEGs). By intersecting these DEGs with inflammatory response-related genes (IRGGs), resulting in the identification of differentially expressed inflammatory response-related genes (DIRRGs). Afterwards, we utilized the protein-protein interaction (PPI) network, machine learning algorithms, namely least absolute shrinkage and selection operator (LASSO) regression and random forest, to identify the signature markers. We employed a nomogram to evaluate the diagnostic effectiveness of the method, which has been confirmed through validation using GSE50223. qRT-PCR was used to confirm the expression of diagnostic genes in clinical samples. In addition, a consensus clustering method was employed to categorize patients with AR. Subsequently, extensive investigation was conducted to explore the discrepancies in gene expression, enriched functions and pathways, as well as potential therapeutic drugs among these distinct subtypes. Results: A total of 22 DIRRGs were acquired, which participated in pathways including chemokine and TNF signaling pathway. Additionally, machine learning algorithms identified NFKBIA, HIF1A, MYC, and CCRL2 as signature genes associated with AR's inflammatory response, indicating their potential as AR biomarkers. The nomogram based on feature genes could offer clinical benefits to AR patients. We discovered two molecular subtypes, C1 and C2, and observed that the C2 subtype exhibited activation of immune- and inflammation-related pathways. Conclusions: NFKBIA, HIF1A, MYC, and CCRL2 are the key genes involved in the inflammatory response and have the strongest association with the advancement of disease in AR. The proposed molecular subgroups could provide fresh insights for personalized treatment of AR.


Assuntos
Rinite Alérgica , Humanos , Rinite Alérgica/diagnóstico , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/genética , Inflamação/tratamento farmacológico , Inflamação/genética , Algoritmos , Análise por Conglomerados , Consenso
2.
Sci Total Environ ; 912: 168880, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38040354

RESUMO

Nitrogen oxides (NOₓ) are primary pollutants produced during biomass combustion. During the devolatilization stage, char nitrogen (char(N)) is formed. In the subsequent char combustion stage, char(N) can decompose directly into NOx precursors or engage in heterogeneous reactions with O2 or NO to form NO and N2. Nonetheless, a comprehensive understanding of the reaction mechanisms and competitiveness of char(N) migration, especially the influence of the alkali metal potassium (K) present in biomass, remains incomplete. Building on the Zigzag char(N) models, the present study delves into the migration reactions of char(N), assessing their competitive dynamics through the integration of density functional theory, electronic structure analysis, and conventional transition state theory. Furthermore, it examines the impact of K on char(N) conversion. The competitiveness of the heterogeneous reactions follows the sequence: heterogeneous reduction of NO to N2 > heterogeneous oxidation of char(N) to NO > decomposition of char(N) to NOx precursors. Moreover, the formation of HCN is more favorable than NH3 production. The successive conversion from char(N) to NO and then to N2 is the predominant migration route for char(N), with NO generation as the pivotal step. The less preferred char(N) migration route involves decomposition to NH3/HCN, followed by oxidation to NOx within the main combustion zone, which cannot be mitigated by char. K can accelerate NO generation and sustain the primacy of the heterogeneous NO reduction, consequently enhancing the oxidation-reduction process of char(N). As a result, K plays a constructive role in managing NOx emissions during the thermal conversion of char.

3.
Ying Yong Sheng Tai Xue Bao ; 34(8): 2153-2160, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37681379

RESUMO

To understand the formation process of typical poisonous plant degraded grassland, we studied the cha-racteristics of vegetation and soil during the gradual expansion of Ligularia virgaurea into the native grassland of Qinghai-Tibet Plateau. The results showed that population density, plant height, coverage, and biomass of L. virgaurea increased during the formation of L. virgaurea degraded grassland. In comparison with native grassland, the degraded grassland had higher total aboveground biomass (113.9%), soil total nitrogen concentration (61.0%), NH4+-N (77.9%), organic carbon concentration (45.3%), available phosphorus concentration (78.8%) as well as soil microbial biomass carbon (42.1%) and nitrogen (47.4%), but lower NO3--N (40.1%) and species richness (28.5%) and aboveground biomass (45.7%) of other species beyond L. virgaurea. The extremely strong abilities of interspecific inhibition and morphological plasticity of L. virgaurea, as well as efficient nutrient accumulation and utilization were the keys to its successful expansion, which facilitated the formation of typical L. virgaurea degraded grassland.


Assuntos
Pradaria , Ligularia , Carbono , Nitrogênio , Solo
4.
Foods ; 11(14)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35885264

RESUMO

In this study, to improve the processing performance of whole grain highland barley flour (whole grain HB flour), they were prepared by sand-roasting, far-infrared baking, steam explosion, and extrusion, and the effects of on functional properties and storage characteristics were measured. The results indicated that sand-roasting, far-infrared baking, and steam explosion all caused cracks and honeycomb structures in the outer layer and endosperm of the highland barley. The XRD analysis results indicated that highland barley starch treated by far-infrared baking exhibited typical A-type crystal structure, while sand-roasting, steam explosion, and extrusion presented the typical V-type. The results of DSC analysis revealed that the onset temperature (To), peak temperature (Tp), gelatinization enthalpy (ΔH), peak viscosity (PV), trough viscosity (TV), and final viscosity (FV) decreased significantly, while the swelling power, water-holding capacity and oil-holding capacity increased significantly. During the storage period, the moisture content and lipase activity of the whole grain HB flour after thermal treatment remained at a low level; the fatty acid value, peroxide value, and malondialdehyde value increased; finally, the cooked whole grain HB flour was unstable during storage. The functional properties of whole grain HB flour can be improved by steam explosion, and will then have better storage stability.

5.
Foods ; 11(14)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35885267

RESUMO

The nutritional composition, polyphenol and anthocyanin composition, and antioxidant capacity of 52 colored highland barley were evaluated. The results showed that the protein content of highland barley in the black group was the highest, the total starch and fat contents in the blue group were the highest, the amylose content in the purple group was quite high, the fiber content in the yellow group was quite high, and the ß-glucan content of the dark highland barley (purple, blue and black) was quite high. The polyphenol content and its antioxidant capacity in the black group were the highest, while the anthocyanin content and its antioxidant capacity in the purple highland barley were the highest. Ten types of monomeric phenolic substances were the main contributors to DPPH, ABTS, and FRAP antioxidant capacity. All varieties could be divided into four categories according to nutrition or function. The grain color could not be used as an absolute index to evaluate the quality of highland barley, and the important influence of variety on the quality of highland barley also needed to be considered. In actual production, suitable raw materials must be selected according to the processing purpose and variety characteristics of highland barley.

6.
Kaohsiung J Med Sci ; 38(4): 312-320, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34989116

RESUMO

This study is aimed at exploring the biological functions and related mechanism of long noncoding RNA 704 (LINC00704) in the proliferation and cell cycle progression of nasopharyngeal carcinoma (NPC) cells. The expression of LINC00704 in NPC tissues and cells was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). After LINC00704 was overexpressed or knocked down in NPC cell lines, cell counting kit-8 (CCK-8) assay, 5-bromo-2'-deoxyuridine assay, flow cytometry assay, and Transwell assay were adopted to detect the proliferation, cell cycle progression, migration, and invasion of NPC cells. The interaction between LINC00704 and ETS proto-oncogene 1 (ETS1) was verified by bioinformatics analysis, RNA pull-down assay, and RNA immunoprecipitation assay. Dual-luciferase reporter gene assay and chromatin immunoprecipitation followed by qPCR analysis were used to verify the binding status between ETS1 and the promoter region of cyclin-dependent kinase 6 (CDK6). The regulatory effects of LINC00704 and ETS1 on CDK6 expression were detected by Western blot. LINC00704 expression was elevated in NPC tissues and cells, which was significantly correlated with the advanced TNM stage and poor differentiation. LINC00704 overexpression promoted the multiplication, migration, and invasion of NPC cells and blocked the cell cycle progression while knocking down LINC00704 worked oppositely. LINC00704 could bind to ETS1, thus promoting CDK6 transcription. Knocking down LINC00704 inhibited the CDK6 expression in NPC cells. LINC00704 promotes CDK6 transcription by recruiting ETS1 to the promoter region of CDK6, thus promoting the malignant progression of NPC.


Assuntos
Neoplasias Nasofaríngeas , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Quinase 6 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteína Proto-Oncogênica c-ets-1/genética , Proteína Proto-Oncogênica c-ets-1/metabolismo
7.
Nat Commun ; 12(1): 3321, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059669

RESUMO

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations are noted in ASD patients and animal models. However, whether astrocyte dysfunction is causal or consequential to ASD-like phenotypes in mice is unresolved. Type 2 inositol 1,4,5-trisphosphate 6 receptors (IP3R2)-mediated Ca2+ release from intracellular Ca2+ stores results in the activation of astrocytes. Mutations of the IP3R2 gene are associated with ASD. Here, we show that both IP3R2-null mutant mice and astrocyte-specific IP3R2 conditional knockout mice display ASD-like behaviors, such as atypical social interaction and repetitive behavior. Furthermore, we show that astrocyte-derived ATP modulates ASD-like behavior through the P2X2 receptors in the prefrontal cortex and possibly through GABAergic synaptic transmission. These findings identify astrocyte-derived ATP as a potential molecular player in the pathophysiology of ASD.


Assuntos
Trifosfato de Adenosina/metabolismo , Astrócitos/patologia , Transtorno do Espectro Autista/patologia , Sinalização do Cálcio/fisiologia , Receptores de Inositol 1,4,5-Trifosfato/deficiência , Animais , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/fisiopatologia , Comportamento Animal , Cálcio/metabolismo , Modelos Animais de Doenças , Neurônios GABAérgicos/fisiologia , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Masculino , Camundongos , Camundongos Knockout , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Transmissão Sináptica/fisiologia
8.
J Int Med Res ; 49(4): 300060521995273, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33866841

RESUMO

OBJECTIVE: To examine the clinical effects of revision endoscopic frontal sinus surgery (RESS) through modified agger nasi (MAN)-middle turbinate resection on refractory chronic rhinosinusitis (CRS). METHODS: We reviewed 156 patients who were treated for refractory CRS from February 2012 to August 2014. These patients had been diagnosed with refractory CRS by computed tomography and endoscopy and had received several surgical and medical treatments in the past, but their condition had not been cured. They were divided into the observation group (RESS through MAN-middle turbinate resection, n = 78) and the control group (endoscopic sinus surgery, n = 78). Complete or partial control of the patient's symptoms and signs suggested that the treatment was effective, and no improvement in the symptoms and signs indicated that the treatment was ineffective. RESULTS: The 6-month treatment efficacy rate was significantly higher in the observation group (91.03%) than in the control group (71.79%). The observation group had a significantly lower complication rate (7.69%) and recurrence rate (3.85%) than the control group (17.95% and 12.82%, respectively). CONCLUSION: RESS through MAN-middle turbinate resection together with adequate perioperative preparation has a significant effect on the outcome of refractory CRS and is worthy of clinical promotion.


Assuntos
Endoscopia/métodos , Seio Frontal/cirurgia , Sinusite Frontal/cirurgia , Procedimentos Cirúrgicos Nasais/métodos , Rinite/cirurgia , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Seio Frontal/diagnóstico por imagem , Sinusite Frontal/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Estudos Retrospectivos , Rinite/diagnóstico por imagem , Resultado do Tratamento , Conchas Nasais/diagnóstico por imagem , Conchas Nasais/cirurgia
9.
Med Sci Monit ; 27: e926990, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33529177

RESUMO

Obstructive sleep apnea (OSA) is defined by intermittent and recurrent episodes of partial or complete obstruction of the upper airway during sleep. Intermittent and recurrent hypoxia/reoxygenation is the main pathophysiological mechanism of OSA. Its consequences include systemic inflammation, activation of the sympathetic nervous system, and release of oxygen free radicals. Infusion of intravenous (IV) lidocaine has anti-inflammatory, antihyperalgesic, and analgesic properties, supporting its use as an anesthetic adjuvant. Lidocaine can reduce nociception and/or cardiovascular responses to surgical stress, as well as postoperative pain and/or analgesic requirements. Because of the high prevalence of OSA in obese patients, the use of opioids to manage postoperative pain in that population is often accompanied by the development of adverse respiratory events, such as hypoventilation and hypoxemia. IV infusion of lidocaine has been shown to enhance the quality of early recovery after laparoscopic bariatric and upper airway surgery. However, limited evidence exists regarding its use in patients undergoing surgery for OSA. In addition, whether IV infusion of lidocaine can improve postoperative early recovery in patients undergoing surgery for OSA remains unknown. Therefore, we hypothesized that IV infusion of lidocaine can improve postoperative early recovery in patients undergoing surgery for OSA. Perioperative infusion also may be a promising analgesic adjunct to enhanced recovery after surgery (ERAS) protocols.


Assuntos
Período de Recuperação da Anestesia , Lidocaína/uso terapêutico , Apneia Obstrutiva do Sono/cirurgia , Analgésicos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Anestésicos Locais/uso terapêutico , Humanos , Infusões Intravenosas/métodos , Lidocaína/administração & dosagem , Medição da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Polissonografia/métodos , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório
10.
Laryngoscope ; 131(1): E63-E69, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32119135

RESUMO

OBJECTIVES/HYPOTHESIS: Systemic infusions of lidocaine have been widely used as perioperative analgesic adjuvants. The aim of this randomized, double-blinded, controlled trial was to investigate the effect of perioperative lidocaine infusion on postoperative early recovery quality in upper airway surgery. STUDY DESIGN: Prospective, randomized, double-blinded, placebo-controlled trial. METHODS: A total of 99 patients were randomly assigned to the lidocaine group (group L) or the control group (group C). The patients received 2 mg/kg lidocaine completed within 10 minutes before the induction of anesthesia followed by continuous infusions of 2 mg/kg/hr lidocaine (group L) or the same volume of 0.9% normal saline (group C) intravenously during anesthesia. The Quality of Recovery-40 (QoR-40) survey was administered on the preoperative day (Pre) and postoperative days 1 (POD1) and 2 (POD2). The primary endpoint was QoR-40 score on POD1 and POD2. RESULTS: Compared with Pre, global QoR-40 scores on POD1 and POD2 were significantly lower (P < .05). Compared with group C, global QoR-40 scores were significantly higher in group L on POD1 and POD2 (P < .05). Among the five dimensions of QoR-40, the scores for physical comfort, emotional state, and pain were superior in group L compared to group C (P < .05). Compared with group C, the consumption of remifentanil and diclofenac as well as the incidence of postoperative nausea and vomiting (PONV) and postoperative 48-hour numeric rating scale (NRS) scores in group L were significantly lower (P < .05). CONCLUSIONS: Systemic lidocaine infusion can improve QoR-40 scores in patients with upper airway surgery, reduce the dosage of intraoperative opioids, decrease the incidence of PONV and NRS scores 2 days after surgery, thus improving postoperative early recovery quality. LEVEL OF EVIDENCE: 1b Laryngoscope, 131:E63-E69, 2021.


Assuntos
Analgésicos/administração & dosagem , Laringe/cirurgia , Lidocaína/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Tonsila Palatina/cirurgia , Seios Paranasais/cirurgia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Cuidados Pré-Operatórios , Adulto , Autoavaliação Diagnóstica , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
11.
Pharmaceutics ; 12(11)2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33207577

RESUMO

The lack of optimal methods employing nanoparticles to administer local anesthesia often results in posing severe risks such as non-biocompatibility, in vivo cytotoxicity, and drug overdose to patients. Here, we employed magnetic field-induced hyperthermia to achieve localized anesthesia. We synthesized iron-gold alloy nanoparticles (FeAu Nps), conjugated an anesthetic drug, Lidocaine, and coated the product with gelatin to increase the biocompatibility, resulting in a FeAu@Gelatin-Lidocaine nano-complex formation. The biocompatibility of this drug-nanoparticle conjugate was evaluated in vitro, and its ability to trigger local anesthesia was also evaluated in vivo. Upon exposure to high-frequency induction waves (HFIW), 7.2 ± 2.8 nm sized superparamagnetic nanoparticles generated heat, which dissociated the gelatin coating, thereby triggering Lidocaine release. MTT assay revealed that 82% of cells were viable at 5 mg/mL concentration of Lidocaine, indicating that no significant cytotoxicity was induced. In vivo experiments revealed that unless stimulated with HFIW, Lidocaine was not released from the FeAu@Gelatin-Lidocaine complex. In a proof-of-concept experiment, an intramuscular injection of FeAu@Gelatin-Lidocaine complex was administered to the rat posterior leg, which upon HFIW stimulation triggered an anesthetic effect to the injected muscle. Based on our findings, the FeAu@Gelatin-Lidocaine complex can deliver hyperthermia-induced controlled anesthetic drug release and serve as an ideal candidate for site-specific anesthesia administration.

12.
Nutr Metab (Lond) ; 17: 83, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33005209

RESUMO

BACKGROUND: The relationships between apolipoprotein A-I (APOA-I), apolipoprotein B (APOB) with insulin resistance, metabolic syndrome (MetS) are unclear in OSA. We aimed to evaluate whether the multiple single nucleotide polymorphism (SNP) variants of APOA-I and APOB exert a collaborative effect on insulin resistance and MetS in OSA. METHODS: Initially, 12 APOA-I SNPs and 30 APOB SNPs in 5259 subjects were examined. After strict screening, four APOA-I SNPs and five APOB SNPs in 4007 participants were included. For each participant, the genetic risk score (GRS) was calculated based on the cumulative effect of multiple genetic variants of APOA-I and APOB. Logistic regression analyses were used to evaluate the relationships between APOA-I/APOB genetic polymorphisms, insulin resistance, and MetS in OSA. RESULTS: Serum APOB levels increased the risk of insulin resistance and MetS adjusting for age, gender and BMI [odds ratio (OR = 3.168, P < 0.001; OR = 6.098, P < 0.001, respectively]. APOA-I GRS decreased the risk of insulin resistance and MetS after adjustments (OR = 0.917, P = 0.001; OR = 0.870, P < 0.001, respectively). APOB GRS had no association with insulin resistance (OR = 1.364, P = 0.610), and had weak association with MetS after adjustments (OR = 1.072, P = 0.042). In addition, individuals in the top quintile of the APOA-I genetic score distribution had a lower risk of insulin resistance and MetS after adjustments (OR = 0.761, P = 0.007; OR = 0.637, P < 0.001, respectively). CONCLUSIONS: In patients with OSA, cumulative effects of APOA-I genetic variations decreased the risk of insulin resistance and MetS, whereas multiple APOB genetic variations had no associations with insulin resistance and weak association with MetS.

13.
Neurosci Bull ; 36(7): 705-718, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32166647

RESUMO

Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABAB receptors (GABABRs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABABRs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABABRs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABABR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABABRs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABABRs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.


Assuntos
Astrócitos , Fator Neurotrófico Derivado do Encéfalo , Transtorno Depressivo Maior , Hipocampo , Receptores de GABA-B , Animais , Ansiedade , Astrócitos/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão , Modelos Animais de Doenças , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de GABA-B/metabolismo
14.
RSC Adv ; 11(1): 296-306, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-35423051

RESUMO

The development of novel wastewater treatment processes that use heterogeneous catalysts to activate hydrogen peroxide (H2O2) with bicarbonate (HCO3 -) has been a subject of great interest in recent years; however, significant challenges remain, despite research into numerous metal-based catalysts. The work presented herein employed oxygen-doped graphitic carbon nitride (O/g-C3N4) as a non-metal catalyst for activating H2O2 in the presence of HCO3 -, and this method represented the first system capable of removing organic pollutants in the dark, to our knowledge. The catalysts were characterized using several microscopic imaging, spectroscopic, electrochemical, and crystallographic techniques, as well as N2-physorption procedures. Analysis of the results revealed that the O/g-C3N4 catalyst possessed a high specific surface area and many defect sites. Various operational parameters, including the relative amounts of HCO3 -, H2O2, and O/g-C3N4, were systemically investigated. A clear performance enhancement was observed in the degradation of organic contaminants when subjected to the HCO3 --H2O2-O/g-C3N4 system, and this result was ascribed to the synchronous adsorption and chemical oxidation processes. The novel system presented herein represented a new water treatment technology that was effective for removing organic contaminants.

15.
Neuroscience Bulletin ; (6): 705-718, 2020.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-826791

RESUMO

Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABA receptors (GABARs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABARs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABARs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABAR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABARs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABARs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.

16.
J Pak Med Assoc ; 69(11): 1610-1616, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31740865

RESUMO

OBJECTIVE: To investigate the prevalence of coronary artery disease and characteristics of coronary artery in patients with obstructive sleep apnoea. METHODS: The prospective study was conducted at the Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China, from January, 2012, to June, 2015, and comprised consecutive patients with diagnosed obstructive sleep apnoea. High-resolution 320-slice coronary computed tomography was performed in all the patients. Data was evaluated for the presence of coronary lumen narrowing. Demographic, clinical, laboratory, and echocardiographic characteristics were carefully recorded. Logistic regression was used for multivariate analysis of independent risk factors. SPSS 16 was used for data analysis. RESULTS: Of the 277 patients, 186(67.14%) were males. The overallmean age was 55.1±14.3 years. Coronary artery disease was found in 41(14.8%) patients. Prospective Cardiovascular Münster score, uric acid, triglyceride, C-reactive protein, apnoea hypopnoea index, Epworth sleepiness scale values were significantly higher in patients with the disease (p<0.05 each). Higher Prospective Cardiovascular Münster score, C-reactive protein, apnoea hyponoea index levels had a significant ability to reflect the occurrence of coronary artery disease (p<0.05 each). CONCLUSIONS: Coronary heart disease occurrence in obstructive sleep apnoea patients was found to be strongly related to Prospective Cardiovascular Münster score, apnoea hyponoea index and Creactive protein level.


Assuntos
Estenose Coronária , Apneia Obstrutiva do Sono , Adulto , Idoso , China , Angiografia por Tomografia Computadorizada , Estenose Coronária/complicações , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/epidemiologia , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Curva ROC , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia
17.
Diabetes Ther ; 10(4): 1357-1368, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172456

RESUMO

OBJECTIVE: This study aimed to explore the association of obstructive sleep apnea-hypopnea syndrome (OSAHS) hypoxia indicators with early renal injury and serum fibroblast growth factor 21 (FGF21) in obese type 2 diabetic patients. METHODS: A total of 109 obese patients with type 2 diabetes mellitus (T2DM) were recruited, including 70 males and 39 females, with an average age of 52.77 ± 13.57 years and average BMI of 29.08 ± 4.36 kg/m2. Overnight sleep monitoring was performed with a portable monitor to record respiratory parameters [apnea-hypopnea index (AHI), oxygen desaturation index (ODI), lowest oxygen saturation (LSaO2), mean oxygen saturation (MSaO2/MPO2) and cumulative time of oxygen saturation < 90% (CT < 90%)]. Ultrasonography was done to detect the quantitative liver fat content (LFC). The urine microalbumin and creatinine ratio (ACR) were determined by immunoturbidimetry. FGF21 was measured at baseline by enzyme-linked immunosorbent assay. Patients were divided into the proteinuria group (n = 42) and non-proteinuria group (n = 67). Correlation analysis and multivariate linear regression analysis were used to analyze the related data. In addition, patients were divided into the T2DM without OSAHS group (n = 16) and T2DM with OSAHS group (n = 93) according to the AHI value. The correlation analysis was used to assess the relationship between FGF21 and clinical variables. RESULTS: (1) ACR positively correlated with waist circumference (WC), AHI, ODI, CT < 90% and LFC, but negatively with MSaO2 and LSaO2. (2) AHI, ODI, CT < 90% and LFC were independent risk factors for ACR, LSaO2 and MSaO2 was a protective factor. (3) Serum FGF21 decreased in the OSAHS group compared with the non-OSAHS group. After adjustment for age, WC and TG, FGF21 correlated negatively with AHI, but positively with MSaO2. CONCLUSIONS: AHI, ODI, CT < 90% and LFC are independent risk factors for ACR. FGF21 is associated with hypoxia indicators, and improving OSAHS status and reducing liver fat content may be helpful for the prevention and treatment of early diabetic nephropathy (DN). CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-IOR-15006225.

18.
J Cell Biochem ; 120(6): 10707-10714, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30816582

RESUMO

Migration and invasion are often recognized as the main reasons for the high recurrence and death rates of glioma and limit the efficacy of surgery and other antitumor therapies. In this study, we found over activation of heat shock cognate protein 70 (Hsc70) in human glioma specimens, which was closely related to glioma grade. We investigated whether Hsc70 induced the migration and invasion of glioma cells. Wound healing and transwell migration assay were used to determine the migration and invasion ability of human glioma U251 and U87 cells, in which the expression of Hsc70 was knocked down by small interfering RNA. Western blot analysis was performed to determine the expression of FAK-Src signaling in malignant glioma cells. The results showed that Hsc70 deficiency significantly retarded migration and invasion and reduced the phosphorylation of FAK, Src, and Pyk2 in U251 and U87 cells. Overall, our results indicate that the migration and invasion capacity of human brain glioma cells is at least partly induced by Hsc70-dependent activation of FAK-Src signaling.


Assuntos
Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Proteínas de Choque Térmico HSC70/genética , Neuroglia/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Quinase 2 de Adesão Focal/genética , Quinase 2 de Adesão Focal/metabolismo , Glioma/metabolismo , Glioma/patologia , Glioma/cirurgia , Proteínas de Choque Térmico HSC70/antagonistas & inibidores , Proteínas de Choque Térmico HSC70/metabolismo , Humanos , Metástase Linfática , Gradação de Tumores , Invasividade Neoplásica , Neuroglia/patologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Quinases da Família src/genética , Quinases da Família src/metabolismo
19.
Sleep Breath ; 23(3): 735-740, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30426457

RESUMO

PURPOSE: Our study aims to compare the difference in clinical efficacy between auto-trilevel positive airway pressure (auto-trilevel PAP) ventilator and conventional fixed bilevel positive airway pressure (BiPAP) ventilator for obesity hypoventilation syndrome (OHS) patients with coexisting moderate or severe obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Twenty-three OHS patients with moderate or severe OSAHS enrolled between January 2015 and September 2017 underwent ventilation by three different modes of positive airway pressure (PAP) for 8 h per night. A single variable mode was applied at the first night followed by two nights when no PAP therapy was carried out as a washout period between each mode. The inspiratory positive airway pressure (IPAP) decided by PaCO2 was consistently used for modes 1, 2, and 3. In mode 1, the expiratory positive airway pressure (EPAP) issued by BiPAP was decided by the minimal PAP levels for cessation of snoring. However, in mode 2, the EPAP was fixed at 3 cmH2O higher than this value. With the use of auto-trilevel PAP in mode 3, the EPAP was set to initially match that of mode 1 but the end of EPAP (EEPAP) was automatically regulated to be elevated according to upper airway patency condition. We also compared the following parameters including apnea hypopnea index (AHI), minimal SpO2 (miniSpO2), arousal index, and sleep efficiency during sleep; PaCO2 in the morning and Epword sleepiness score (ESS) at daytime were measured prior to and during PAP treatment as well as between three selected PAP modes. RESULTS: Compared with the parameters before ventilation therapies, all three variable modes of ventilation were associated with a higher nocturnal miniSpO2 and sleep efficiency (all P < 0.01). Among the three variable modes, mode 3 resulted in not only the lowest arousal index and daytime ESS but also the highest sleep efficiency. Compared to mode 1, mode 2 demonstrated a significantly reduced AHI and an elevated miniSpO2 and morning PaCO2 (all P < 0.05), while mode 3 was associated with a decreased AHI, an increased miniSpO2 (all P < 0.05), and no statistical change of PaCO2 following the end of PAP treatment (P > 0.05). Comparison between mode 2 and mode 3 revealed that mode 3 had a significantly lower PaCO2 (P < 0.05), but displayed no remarkable changes of AHI and miniSpO2 (all P > 0.05). CONCLUSION: Compared to fixed BiPAP ventilation, auto-trilevel PAP ventilation could more effectively correct hypercapnia, achieve lower index of nocturnal apnea and hypopnea, more improved sleep quality, and lower daytime sleepiness score. Auto-trilevel PAP ventilation is therefore more efficacious than conventional BiPAP ventilation in non-invasive ventilation therapy for OHS patients with concurrent moderate or severe OSAHS.


Assuntos
Ventilação com Pressão Positiva Intermitente/métodos , Síndrome de Hipoventilação por Obesidade/terapia , Respiração com Pressão Positiva/métodos , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Síndromes da Apneia do Sono/terapia , Resultado do Tratamento
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-818915

RESUMO

This paper reports one case of gastric antral ulcer due to Strongyloides stercoralis infection in Leshan Traditional Chinese Medicine Hospital.

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