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3.
Diagn Microbiol Infect Dis ; 109(4): 116374, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38805857

RESUMEN

Whipple's disease is a chronic systemic infectious disease that mainly affects the gastrointestinal tract. In some cases, Tropheryma whipplei can cause infection at the implant site or even throughout the body. In this study, we collected alveolar lavage fluid samples from patients with Tropheryma whipplei from 2020 to 2022, and retrospectively analyzed the clinical data of Tropheryma whipplei positive patients. Patient's past history, clinical manifestations, laboratory examinations, chest CT findings, treatment, and prognosis were recorded. 16 BALFs (70/1725, 4.0 %) from 16 patients were positive for Tropheryma whipplei. 8 patients were male with an average age of 50 years. The main clinical symptoms of patients included fever (9/16), cough (7/16), dyspnea (7/16), and expectoration (5/16), but neurological symptoms and arthralgia were rare. Cardiovascular and cerebrovascular diseases were the most common comorbidity (n=8). The main laboratory characteristics of the patient are red blood cell count, hemoglobin, total protein and albumin below normal levels (11/16), and/or creatinine above normal levels(14/16). Most chest computed tomography mainly show focal or patchy heterogeneous infection (n=5) and pleural effusion (n=8). Among the 6 samples, Tropheryma whipplei was the sole agent, and Klebsiella pneumoniae was the most common detected other pathogens. Metagenomic next-generation sequencing technology has improved the detection rate and attention of Tropheryma whipplei. Further research is needed to distinguish whether Tropheryma whipplei present in respiratory samples is a pathogen or an innocent bystander.

5.
Infect Drug Resist ; 17: 1439-1445, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38628241

RESUMEN

Background: The HACEK group comprises Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae, are Gram-negative bacteria that are slow-growing and fastidious. These organisms are common causes of culture-negative endocarditis. However, brain abscesses caused by Haemophilus aphrophilus and E. corrodens have been rarely reported. The case we describe, which was promptly identified and successfully treated, will be meaningful for the diagnosis and treatment of such infectious diseases. Case Presentation: Herein, we report a case of brain abscess in a young man who was infected with Haemophilus aphrophilus and E. corrodens. The patient was admitted to the hospital with sudden onset of vomiting, coma, and fever. Magnetic resonance imaging (MRI) of the brain and cerebrospinal fluid cell counts suggested cerebral abscess, he underwent drainage of the abscess and empirical antimicrobial therapy of meropenem (2 g every 8 hours) and linezolid (0.6 g every 12 hours) for more than 10 days without significant improvement. Metagenomic next-generation sequencing (mNGS) of drainage fluid and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) detection for isolated bacteria from samples suggested the presence of H. aphrophilus and E. corrodens. After 7 weeks of ceftriaxone (2 g every 12 hours) and meropenem (2 g every 8 hours) intravenously, the patient was discharged with a normal temperature and brain MRI showed improvement of the lesion. Conclusion: Similar cases reported in previous studies were always associated with bacterial blood dissemination after dental surgery or myocarditis; however, the patient in our case had no any associated risk factors. As far as we know, this is the only case of central nervous system infection caused by H. aphrophilus and E. corrodens that has utilized combined mNGS and MALDI-TOF MS in the diagnosis.

6.
BMC Microbiol ; 24(1): 86, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38481150

RESUMEN

INTRODUCTION: Psittacosis is a zoonosis caused by Chlamydia psittaci, the clinical manifestations of Psittacosis range from mild illness to fulminant severe pneumonia with multiple organ failure. This study aimed to evaluate the clinical characteristics of Chlamydia psittaci infection diagnosed based on metagenomic next-generation sequencing(mNGS), as well as the risk factors affecting the progress of Chlamydia psittaci infection, in order to improve the effect of therapeutics. METHODS: We retrospectively analyzed the clinical data of patients infected with chlamydia psittaci in the First Affiliated Hospital of Nanchang University from January 2021 to December 2021. The patient's past medical history, clinical manifestations, laboratory examinations, chest CT results, treatment status, and prognosis data were collected. we also investigated both the pathogenic profile characteristics and the lower respiratory tract microbiota of patients with Chlamydia psittaci pneumonia using mNGS. RESULTS: All cases of Chlamydia psittaci in our research have been confirmed by mNGS. Among 46 cases of Chlamydia psittaci pneumonia, Poultry exposure was reported in 35 cases. In severe cases of Chlamydia psittaci pneumonia, Neutrophils, Procalcitonin (PCT), Lactate Dehydrogenase (LDH), Hydroxybutyrate Dehydrogenase (HBDH), Creatine Kinase Isoenzymes-B (CK-MB) and D-Dimer levels were remarkably higher than that of non-severe cases, except for lymphocytes (all P < 0.05). Chest CT scans showed Bilateral (77.8%), multiple lobar lungs (85.2%), pleural effusions (44.4%) involvement in those suffering from severe Chlamydia psittaci pneumonia, whereas its incidence was 0%, 21.1% and 10.5% in non-severe patients, respectively (P < 0.05). Multivariate analysis revealed that higher lymphocyte concentrations (OR 0.836, 95% CI 0.714-0.962, P = 0.041) were the only protective factor for survival. mNGS results indicated that 41.3% of patients (19/46) had suspected coinfections with a coinfection rate of 84.2% (16/19) in the severe group, much higher than that in the non severe group (p < 0.05). No significantly different profiles of lower respiratory tract microbiota diversity were found between non severe group and severe group. CONCLUSION: A history of poultry exposure in patients can serve as an important basis for diagnosing Chlamydia psittaci pneumonia, and patients with severe Chlamydia psittaci pneumonia are more likely to develop elevated inflammatory biomarkers as well as elevated cardiac markers. Higher lymphocyte concentrations are protective factors associated with severe C. psittaci pneumonia. The higher proportion of patients with coinfections in our study supports the use of mNGS for comprehensive early detection of respiratory infections in patients with C. psittaci pneumonia.


Asunto(s)
Chlamydophila psittaci , Coinfección , Neumonía , Psitacosis , Humanos , Psitacosis/diagnóstico , Chlamydophila psittaci/genética , Estudios Retrospectivos , Secuenciación de Nucleótidos de Alto Rendimiento , Factores de Riesgo
7.
Lab Med ; 55(2): 132-139, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-37289931

RESUMEN

OBJECTIVE: Metagenomic next-generation sequencing (mNGS) can be used to detect pathogens in clinical infectious diseases through the sequencing analysis of microbial and host nucleic acids in clinical samples. This study aimed to assess the diagnostic performance of mNGS in patients with infections. METHODS: In this study, 641 patients with infectious diseases were enrolled. These patients simultaneously underwent pathogen detection by both mNGS and microbial culture. Through statistical analysis, we judged the diagnostic performance of mNGS and microbial culture on different pathogens. RESULTS: Among 641 patients, 276 cases of bacteria and 95 cases of fungi were detected by mNGS, whereas 108 cases of bacteria and 41 cases of fungi were detected by traditional cultures. Among all mixed infections, combined bacterial and viral infections were the highest (51%, 87/169), followed by combined bacterial with fungal infections (16.57%, 28/169) and mixed bacterial, fungal, and viral infections (13.61%, 23/169). Among all sample types, bronchoalveolar lavage fluid (BALF) samples had the highest positive rate (87.8%, 144/164), followed by sputum (85.4%, 76/89) and blood samples (61.2%, 158/258). For the culture method, sputum samples had the highest positive rate (47.2%, 42/89), followed by BALF (37.2%, 61/164). The positive rate of mNGS was 69.89% (448/641), which was significantly higher than that of traditional cultures (22.31% [143/641]) (P < .05). CONCLUSIONS: Our results show that mNGS is an effective tool for the rapid diagnosis of infectious diseases. Compared with traditional detection methods, mNGS also showed obvious advantages in mixed infections and infections with uncommon pathogens.


Asunto(s)
Coinfección , Enfermedades Transmisibles , Virosis , Humanos , Enfermedades Transmisibles/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento , Líquido del Lavado Bronquioalveolar , Sensibilidad y Especificidad
8.
Pain Physician ; 26(6): E635-E649, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37847917

RESUMEN

BACKGROUND: Opioid-based general anesthesia was previously used to alleviate perioperative pain; however, several complications associated with using anesthesia have raised several concerns. Various studies have investigated the application prospect of using opioid-free general anesthesia, such as dexmedetomidine, as an opioid substitute. OBJECTIVES: We performed a systematic review and meta-analysis to explore and highlight the safety and effectiveness of dexmedetomidine as an opioid substitute for opioid-free anesthesia. STUDY DESIGN: A systematic review and meta-analysis. SETTING: We screened for suitable clinical trials from electronic databases, including "PubMed," "Cochrane Library," "EMBASE," and "Web of Science." Eligible trials were included in this meta-analysis. METHODS: The quality of the screened randomized controlled trials (RCTs) was determined using the risk of bias assessment criteria by the Cochrane Collaboration tool. We used the "Review Manager 5.3" and "Stata 10.0" software to perform the meta-analysis. We evaluated the quality of evidence using the "Grading of Recommendations Assessment, Development, and Evaluation" approach. RESULTS: For the analysis, we included 32 RCTs encompassing 2,509 patients. In the opioid-free group, the 2-hour postoperative pain score of patients (mean difference = -0.53, 95% CI: -1.00, -0.07; P = 0.02, I2=78%) was significantly lower compared to those in the opioid-based group. In addition, several patients required rescue analgesia (risk ratio = 0.70, 95% CI: 0.58, 0.84, P < 0.05, I2 = 71%) and opioids postsurgery. However, the duration of extubation and postanesthesia care unit, as well as the incidences of bradycardia, were high in patients receiving dexmedetomidine as opioid-free general anesthesia. LIMITATIONS: Subgroup analysis for different anesthesia-maintaining drugs had not been conducted. The heterogeneity did not reduce after subgroup analysis. Different doses of dexmedetomidine had not been evaluated. CONCLUSIONS: These findings indicate that opioid-free general anesthesia based on dexmedetomidine could be effective; however, prolonged extubation time and cardiovascular complications are a few risks associated with dexmedetomidine.


Asunto(s)
Analgesia , Dexmedetomidina , Humanos , Dexmedetomidina/uso terapéutico , Analgésicos Opioides/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Anestesia General/efectos adversos
9.
Aging Clin Exp Res ; 35(11): 2323-2331, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37776484

RESUMEN

BACKGROUND: The prophylactic effect of exogenous melatonin and melatonin receptor agonists (MMRAs) on postoperative delirium (POD) in elderly patients remains controversial. OBJECTIVE: This study aimed to assess the prophylactic effect of MMRAs on POD by conducting a systemic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We systematically searched four electronic databases including PubMed, Web of Science, Cochrane Library, and Embase for the eligible studies up to February 28, 2023. The Cochrane risk of bias tool was used for assessing the risk of bias in the included RCTs. The occurrence of POD was the primary outcome. The quality of evidence was evaluated by Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: A total of 11 RCTs comprising patients (MMRA group: 777 patients and placebo group: 781 patients) were included. The results of the meta-analysis showed that the MMRA group had a lower occurrence of POD than the placebo group (risk ratio = 0.70, 95% confidence interval: 0.51-0.97, P < 0.05, I2 = 59%). The subgroup analysis showed that melatonin significantly reduced the occurrence of POD (moderate-quality evidence), whereas ramelteon and tryptophan had no significant impact (moderate-quality evidence). CONCLUSION: Existing evidence suggested that perioperative use of melatonin can prevent POD in elderly patients.


Asunto(s)
Delirio del Despertar , Melatonina , Humanos , Anciano , Delirio del Despertar/prevención & control , Melatonina/uso terapéutico , Receptores de Melatonina , Ensayos Clínicos Controlados Aleatorios como Asunto , Hipnóticos y Sedantes
10.
Pharmaceuticals (Basel) ; 15(12)2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36559039

RESUMEN

Hypotension induced by spinal anaesthesia is a common clinical complication associated with multiple perioperative adverse events. We conducted a systemic review and meta-analysis to confirm whether ondansetron could alleviate hypotension following spinal anaesthesia. PubMed, Embase, Web of Science, and Cochrane Library were searched to identify eligible randomised controlled trials from their respective database inception dates to 30 September 2022. The primary outcome of the meta-analysis was the incidence of hypotension after spinal anaesthesia. The risk of bias in the included studies was evaluated using the revised Cochrane risk of bias tool for randomised trials (RoB 2.0). Grading of Recommendations, Assessment, Development, and Evaluation was applied to assess the level of certainty. A total of 25 studies were included in this research. The meta-analysis revealed that ondansetron significantly decreased the incidence of hypotension (RR = 0.65, 95% CI 0.53−0.80, p < 0.01, I2 = 64%) and bradycardia. In addition, patients treated with ondansetron had a reduced need for vasopressors administration. This study suggests that ondansetron may be recommended as a prophylaxis for hypotension and bradycardia following spinal anaesthesia; the level of evidence was moderate with a high level of heterogeneity.

11.
Neuroscience ; 491: 98-109, 2022 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-35367291

RESUMEN

Our previous studies revealed that miR-34a suppresses autophagy in the ageing cochlea, which correlates with cochlear hair cell loss and age-related hearing loss (AHL). However, the mechanisms underlying miR-34a regulation of autophagy in the cochlea remain unclear. Here, we show that nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagy, was regulated by miR-34a in HEI-OC1 cells. Moreover, ATG9A, one of the main targets of miR-34a, was shown to interact with TFEB and thus promote its nuclear translocation in HEI-OC1 cells. Rapamycin rescued the inhibition of TFEB nuclear translocation induced by miR-34a/ATG9A activation, restored autophagic flux and consequently prevented HEI-OC1 cell death. Long-term supplementation with rapamycin attenuated outer hair cells (OHCs) and inner hair cell synaptic ribbons, and delayed AHL in C57BL/6 mice. Most importantly, rapamycin partially restored TFEB's nuclear localization and autophagic flux in OHCs of the ageing cochlea. These findings open new avenues for protection against AHL through miR-34a/ATG9a/TFEB modulation of autophagy.


Asunto(s)
MicroARNs , Presbiacusia , Animales , Autofagia/fisiología , Proteínas Relacionadas con la Autofagia/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Células Ciliadas Auditivas/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Sirolimus/farmacología , Proteínas de Transporte Vesicular/metabolismo
12.
J Clin Anesth ; 78: 110669, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35151145

RESUMEN

STUDY OBJECTIVE: Emergence agitation (EA) is a common complication in pediatric patients after general anesthesia. The effectiveness of magnesium sulfate in decreasing the incidence of EA in children remains controversial. Therefore, a systematic review and meta-analysis was performed to assess the efficacy of magnesium sulfate in preventing EA in pediatric patients following general anesthesia. DESIGN: Systematic review and meta-analysis. SETTING: PubMed, Embase, Web of Science, and Cochrane Library were searched to identify eligible randomized controlled trials from their respective database inception dates to June 30, 2021. PATIENTS: Pediatric patients (< 18 years old) undergoing general anesthesia. INTERVENTIONS: Intravenous administration of magnesium sulfate. MEASUREMENTS: The primary outcome of the meta-analysis was EA incidence. The risk of bias of the included studies was evaluated using the revised Cochrane risk of bias tool for randomized trials (RoB 2.0). Grading of Recommendations, Assessment, Development, and Evaluation was applied to assess the level of certainty. MAIN RESULTS: Eight studies with 635 participants were identified. The forest plot revealed no significant difference in the incidence of EA between patients treated with magnesium sulfate and the control group (risk ratio = 0.69, 95% confidence interval [0.44, 1.07]; P = 0.10, I2 = 74%, moderate level of certainty). Additionally, magnesium sulfate did not reduce postoperative pediatric anesthesia emergence delirium scores but prolonged the emergence time. No significant differences were observed in postoperative complications (nausea, vomiting, laryngospasm, breath-holding, coughing, oxygen desaturation, and cardiac arrhythmias). CONCLUSIONS: Administration of magnesium sulfate during general anesthesia did not affect the occurrence of EA in pediatric patients. However, magnesium sulfate can prolong the emergence time without adverse effects. PROSPERO registration number: CRD42021252924.


Asunto(s)
Delirio del Despertar , Adolescente , Anestesia General/efectos adversos , Niño , Delirio del Despertar/epidemiología , Delirio del Despertar/etiología , Delirio del Despertar/prevención & control , Humanos , Sulfato de Magnesio/efectos adversos , Náusea/etiología , Vómitos/etiología
13.
Acupunct Med ; 40(4): 360-368, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35034504

RESUMEN

BACKGROUND AND AIM: Disordered hepatic energy metabolism is found in obese rats with insulin resistance (IR). There are insufficient experimental studies of electroacupuncture (EA) for IR and type 2 diabetes mellitus (T2DM). The aim of this study was to probe the effect of EA on disordered hepatic energy metabolism and the adenosine monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/ribosomal protein S6 kinase, 70-kDa (p70S6K) signaling pathway. METHODS: Zucker Diabetic Fatty (ZDF) rats were randomly divided into three groups: EA group receiving EA treatment; Pi group receiving pioglitazone gavage; and ZF group remaining untreated (n = 8 per group). Inbred non-insulin-resistant Zucker lean rats formed an (untreated) healthy control group (ZL, n = 8). Fasting plasma glucose (FPG), fasting insulin (FINS), C-peptide, C-reactive protein (CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) indices were measured. Hematoxylin-eosin (H&E) staining was used to investigate the liver morphologically. The mitochondrial structure of hepatocytes was observed by transmission electron microscopy (TEM). Western blotting was adopted to determine protein expression of insulin receptor substrate 1 (IRS-1), mTOR, mTORC1, AMPK, tuberous sclerosis 2 (TSC2) and p70S6K, and their phosphorylation. RT-PCR was used to quantify IRS-1, mTOR, mTORC1, AMPK and p70S6K mRNA levels. RESULTS: Compared with the ZF group, FPG, FINS, C-peptide, CRP and HOMA-IR levels were significantly reduced in the EA group (p < 0.05, p < 0.01). Evaluation of histopathology showed improvement in liver appearances following EA. Phosphorylation levels of AMPK, mTOR and TSC2 decreased, and IRS-1 and p70S6K increased, in hepatocytes of the ZF group, while these negative effects appeared to be alleviated by EA. CONCLUSIONS: EA can effectively ameliorate IR and regulate energy metabolism in the ZDF rat model. AMPK/mTORC1/p70S6K and related molecules may represent a potential mechanism of action underlying these effects.


Asunto(s)
Diabetes Mellitus Tipo 2 , Electroacupuntura , Resistencia a la Insulina , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Péptido C/metabolismo , Péptido C/farmacología , Diabetes Mellitus Tipo 2/terapia , Metabolismo Energético , Insulina/metabolismo , Mamíferos/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratas , Ratas Zucker , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/farmacología , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/farmacología
14.
Methods Mol Biol ; 2372: 111-121, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34417747

RESUMEN

A highly useful tool for studying lncRNAs is simultaneous RNA-DNA FISH, which reveals the localization and quantitative information of RNA and DNA in cellular contexts. However, a simple combination of RNA FISH and DNA FISH often generates disappointing results because the fragile RNA signals are often damaged by the harsh conditions used in DNA FISH for denaturing the DNA. Here, we describe a robust and simple RNA-DNA FISH protocol, in which amino-labeled nucleic acid probes are used for RNA FISH . The method is suitable to detect single RNA molecules simultaneously with DNA.


Asunto(s)
Hibridación Fluorescente in Situ , ADN/genética , Sondas de Oligonucleótidos , ARN Largo no Codificante/genética
15.
J Clin Anesth ; 75: 110467, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34343737

RESUMEN

STUDY OBJECTIVE: Previous studies reported that controlled low central venous pressure (CVP) can reduce blood loss during liver resection. This systematic review and meta-analysis sought to explore the efficacy and safety of low CVP in patients undergoing hepatectomy. DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). REVIEW METHODS: RCTs were searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical database, Chinese Scientific Journals Database, and Wanfang database from inception to April 30, 2021. Subgroup analyses were performed based on different surgical methods (open hepatectomy vs laparoscopic hepatectomy) and published countries (China vs other countries). The quality of evidence was assessed by Grading of Recommendations, Assessment, Development, and Evaluation. MAIN RESULTS: Eighteen RCTs containing 1285 participants (626 patients in the low CVP group and 659 patients in the control group) were included in this study. The forest plot showed that low CVP effectively reduced blood loss during liver resection compared with the control group (MD = -311.92 mL, 95% CI [-429.03, -194.81]; P < 0.001, I2 = 96%). Furthermore, blood transfusion volume (MD = -158.85 mL, 95% CI [-218.30, -99.40]; P < 0.001, I2 = 55%) and the number of patients requiring transfusion (RR 0.41, 95% CI 0.27-0.65, P < 0.001, I2 = 0%) were decreased in the low CVP group. Subgroup analyses showed similar results. Notably, the alanine transaminase level was significantly lower in the low CVP group during the first five postoperative days. However, no significant differences were observed for other postoperative liver function indicators (aspartate aminotransferase, total bilirubin, serum albumin, and prothrombin time), renal function indicators (blood urea nitrogen and serum creatinine) and perfusion parameters (heart rate, mean arterial pressure, and urine volume). The incidence of complications was similar between the two groups. CONCLUSION: The findings of this study showed that low CVP is effective and safe during hepatectomy. Therefore, this technique is recommended to reduce blood loss during hepatectomy. PROSPERO registration number: CRD42021232829.


Asunto(s)
Hepatectomía , Laparoscopía , Pérdida de Sangre Quirúrgica/prevención & control , Transfusión Sanguínea , Presión Venosa Central , Hepatectomía/efectos adversos , Humanos
16.
Neurosci Bull ; 37(5): 657-668, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33415566

RESUMEN

Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss (NIHL). Given that cellular defense against oxidative stress is an energy-consuming process, the aim of the present study was to investigate whether increasing energy availability by glucose supplementation protects cochlear hair cells against oxidative stress and attenuates NIHL. Our results revealed that glucose supplementation reduced the noise-induced formation of reactive oxygen species (ROS) and consequently attenuated noise-induced loss of outer hair cells, inner hair cell synaptic ribbons, and NIHL in CBA/J mice. In cochlear explants, glucose supplementation increased the levels of ATP and NADPH, as well as attenuating H2O2-induced ROS production and cytotoxicity. Moreover, pharmacological inhibition of glucose transporter type 1 activity abolished the protective effects of glucose against oxidative stress in HEI-OC1 cells. These findings suggest that energy availability is crucial for oxidative stress resistance and glucose supplementation offers a simple and effective approach for the protection of cochlear hair cells against oxidative stress and NIHL.


Asunto(s)
Pérdida Auditiva Provocada por Ruido , Animales , Glucosa/toxicidad , Células Ciliadas Auditivas , Pérdida Auditiva Provocada por Ruido/prevención & control , Peróxido de Hidrógeno/toxicidad , Ratones , Ratones Endogámicos CBA , Estrés Oxidativo
17.
Oncol Lett ; 20(1): 803-809, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32566007

RESUMEN

Alterations in collagen type I α1 (COL1A1) and collagen type I α 2 (COL1A2) expression levels have been reported to predict prognosis in various types of cancer. However, the effect of these biomarkers on hypopharyngeal squamous cell carcinoma (HPSCC) is yet to be fully elucidated. The present study aimed to explore the prognostic significance of COL1A1 and COL1A2 expression levels in HPSCC. The expression levels of COL1A1 and COL1A2 in 67 patients with HPSCC were examined using an immunohistochemical assay in a tissue microarray. The associations between COL1A1/COL1A2 expression levels and patient clinicopathological features were analyzed using ANOVA, Pearson's χ2 or Fisher's exact test. The Cox proportional hazard models and Kaplan-Meier survival analysis with log-rank tests were used to analyze the significance of COL1A1/COL1A2 as prognostic markers for patients with HPSCC. As a result, immunohistochemical staining revealed that COL1A1 was positively expressed in all cases, among which 40.3% were strong positive, while COL1A2 was positively expressed in 76.1% of the HPSCC cases with 6.0% of the samples exhibiting strong staining. Further analysis revealed no significant association between the expression levels of COL1A1/COL1A2 and other clinicopathological features. Cox regression analysis revealed that a high COL1A2 expression level predicted a high locoregional recurrence and a less favorable disease-free survival rate (P=0.042 and 0.020, respectively). Overall, the present study indicated that COL1A2 expression levels may have value as a prognostic indicator in HPSCC.

18.
Toxicol Lett ; 331: 1-10, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32428544

RESUMEN

Cisplatin is a well-known and commonly used chemotherapeutic agent. However, cisplatin-induced ototoxicity limits its clinical use. Previous studies have shown an important role of reactive oxygen species (ROS) accumulation in the pathogenesis of cisplatin-induced ototoxicity. In many cell types, the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant response element (ARE) protect against oxidative stress by suppressing ROS. Here our results showed that cisplatin injury reduced Nrf2 expression and inhibited Nrf2 translocation in HEI-OC1 cells and Nrf2 activator tert-butylhydroquinone (TBHQ) rescued hair cells from cisplatin induced apoptosis by suppressing the total cellular ROS accumulation. Moreover, we found that decreased ROS accumulation induced by TBHQ didn't depend on mitochondrial derived ROS production, indicating that Nrf2 activation alleviated cisplatin induced oxidative stress and apoptosis through mitochondrial-independent ROS production. Therefore, we provide a potential strategy of prevention and treatment for cisplatin-induced ototoxicity by Nrf2 activation. In conclusion, Nrf2 activation protects auditory hair cells from cisplatin-induced ototoxicity through suppressing the total cellular ROS levels which arise from sources other than mitochondria.


Asunto(s)
Antineoplásicos/toxicidad , Cisplatino/toxicidad , Células Ciliadas Auditivas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Ototoxicidad/prevención & control , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Células Ciliadas Auditivas/metabolismo , Hidroquinonas/farmacología , Masculino , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Factor 2 Relacionado con NF-E2/genética , Ototoxicidad/patología , Especies Reactivas de Oxígeno/metabolismo
19.
Oxid Med Cell Longev ; 2019: 6150148, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31781342

RESUMEN

Long noncoding RNA (lncRNA) disorder has been found in many kinds of age-associated diseases. However, the role of lncRNA in the development of age-related hearing loss (AHL) is still largely unknown. This study sought to uncover AHL-associated lncRNAs and the function. RNA-sequencing was conducted to profile lncRNA expression in the cochlea of an early-onset AHL mouse model. RT-qPCR assay was used to validate the expression pattern of lncRNAs. ATP assay, JC-1 assay, mitochondrial probe staining, CCK-8 assay, Western blot, and immunocytochemistry were performed to detect the effects of lncRNA AW112010 in HEI-OC1 cells and the mouse cochlea. We identified 88 significantly upregulated lncRNAs and 46 significantly downregulated lncRNAs in the cochlea of aged C57BL/6 mice. We focused on the significantly upregulated AW112010. Silencing of AW112010 decreased the ATP level, mitochondrial membrane potential, and cell viability and increased mitochondrial ROS generation under oxidative stress in HEI-OC1 cells. AW112010 overexpression promoted cell survival in HEI-OC1 cells. AW112010 knockdown reduced mitochondrial mass and impaired mitochondrial biogenesis in HEI-OC1 cells. Activation of mitochondrial biogenesis by resveratrol and STR1720 promoted cell survival. The mitochondrial biogenesis process was activated in the cochlea of aged mice. Moreover, AW112010 regulated AMPK signaling in HEI-OC1 cells. Transcription factor Arid5b elevated in the aged cochlea and induced AW112010 expression and mitochondrial biogenesis in HEI-OC1 cells. Taken together, lncRNAs are dysregulated with aging in the cochlea of C57BL/6 mice. The Arid5b/AW112010 signaling was induced in the aged mouse cochlea and positively modulated the mitochondrial biogenesis to maintain mitochondrial function.


Asunto(s)
Envejecimiento/metabolismo , Células Ciliadas Auditivas/metabolismo , Pérdida Auditiva/metabolismo , Mitocondrias/metabolismo , Biogénesis de Organelos , ARN Largo no Codificante/biosíntesis , Transducción de Señal , Adenosina Trifosfato/metabolismo , Envejecimiento/genética , Envejecimiento/patología , Animales , Supervivencia Celular/efectos de los fármacos , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Silenciador del Gen , Células Ciliadas Auditivas/patología , Pérdida Auditiva/genética , Pérdida Auditiva/patología , Ratones , Mitocondrias/genética , Mitocondrias/patología , ARN Largo no Codificante/genética , Resveratrol/farmacología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
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