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Depression is a common occurrence among cancer patients, and it significantly impacts their clinical outcomes and quality of life, with a high incidence during anti-tumor treatment or after surgery. The association between surgery and depression is the result of the interaction of various factors, including physiological, psychological, and social factors, all of which are intertwined and make patients susceptible to depression after surgical treatment. Postoperative depression has a significant negative impact on many aspects of cancer patients, and it requires timely identification and intervention to improve the overall outcome.
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OBJECTIVES: The prognosis of patients with Small Cell Lung Cancer (SCLC) can be predicted by their Lymph Node (LN) status. The authors aimed to assess the correlations between SCLC survival and number of LN Ratio (LNR), positive LN (pLNs), and Logarithmic Odds of positive LN (LODDS). METHODS: This cohort study retrospectively included 1,762 patients with SCLC from the SEER database 2004â2015. The X-tile software was used to determine the cutoff values for pLNs, LNR, and LODDS. The correlations between pLNs, LNR, and LODDS with Overall Survival (OS) and Cancer-Specific Survival (CSS) were explored using Cox regression analysis. The study used the C-index to assess the predictive value of LNR, pLNs, and LODDS on survival. RESULTS: Among these 1,762 patients, 121 (6.87%) were alive, 1,641 (93.13%) died, and 1,532 (86.95%) died of SCLC. In univariable COX analysis, LNR, pLNs, and LODDS all showed a correlation with CSS and OS (p < 0.05). In multivariable COX analysis, only patients with LODDS (> 0.3 vs. ≤ 0.3) were related to both worse OS (HR = 1.28, 95% CI 1.10â1.50) and CSS (HR = 1.29, 95% CI 1.10â1.51), but no correction was observed between LNR and pLNs and survival (p > 0.05). The C-indices for predicting OS for LODDS were 0.552 (95% CI 0.541â0.563), for LNR 0.504 (95% CI 0.501â0.507), and for pLNs 0.527 (95% CI 0.514â0.540). Moreover, the association between LODDS and prognosis in SCLC patients was significant only in patients with LN stage N1 and N2, but not in stage N3. CONCLUSION: LODDS may be better than other LN assessment tools at predicting survival in SCLC patients.
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Neoplasias Pulmonares , Ganglios Linfáticos , Metástasis Linfática , Programa de VERF , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/patología , Masculino , Femenino , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Ganglios Linfáticos/patología , Pronóstico , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Adulto , Estimación de Kaplan-MeierRESUMEN
OBJECTIVE: Numerous studies have reported the close association of depression with obstructive sleep apnea (OSA). However, the causal nature and direction remain unclear. This study aimed to identify the genetic causal relationship between depression and OSA using Mendelian randomization (MR). METHODS: Based on publicly available genome-wide association studies data of depression and OSA, we conducted a bidirectional two-sample MR study. The inverse-variance weighted (IVW) was used as the main analysis method. Moreover, multivariable MR was performed to further explore the underlying genetic causality of OSA and depression after adjusting for several potential mediators. RESULTS: The univariable MR analysis revealed a significant causality of depression on the susceptibility of OSA (ORivw = 1.29, 95%CI:1.11,1.50; p < 0.001). This relationship was evidenced by the phenotypes for broad depression (ORivw = 3.30, 95%CI: 1.73, 6.29; p < 0.001), probable major depression (ORivw = 18.79, 95%CI: 5.69, 61.99; p < 0.001), and ICD-10 major depression (ORivw = 23.67, 95%CI: 4.13, 135.74; p < 0.001). In the reverse direction, no significant causal effect of OSA on depression was found. After adjusting for smoking, alcohol use, obesity, type 2 diabetes, insomnia, age, gender, and codeine, most of these results suggested that depression remained significantly and positively associated with OSA. CONCLUSION: These findings may contribute to the understanding of the etiology of depression and OSA and also suggest the clinical significance of controlling depression for the prevention of OSA.
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Trastorno Depresivo Mayor , Diabetes Mellitus Tipo 2 , Apnea Obstructiva del Sueño , Humanos , Depresión/epidemiología , Depresión/genética , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/genética , Masculino , FemeninoRESUMEN
Obstructive sleep apnea (OSA) is a common respiratory disorder. Multiple organs, especially the central nervous system (CNS), are damaged, and dysfunctional when intermittent hypoxia (IH) occurs during sleep for a long time. The quality of life of individuals with OSA is significantly impacted by cognitive decline, which also escalates the financial strain on their families. Consequently, the development of novel therapies becomes imperative. IH induces oxidative stress, endoplasmic reticulum stress, iron deposition, and neuroinflammation in neurons. Synaptic dysfunction, reactive gliosis, apoptosis, neuroinflammation, and inhibition of neurogenesis can lead to learning and long-term memory impairment. In addition to nerve injury, the role of IH in neuroprotection was also explored. While causing neuron damage, IH activates the neuronal self-repairing mechanism by regulating antioxidant capacity and preventing toxic protein deposition. By stimulating the proliferation and differentiation of neural stem cells (NSCs), IH has the potential to enhance the ratio of neonatal neurons and counteract the decline in neuron numbers. This review emphasizes the perspectives and opportunities for the neuroprotective effects of IH and informs novel insights and therapeutic strategies in OSA.
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Hipoxia , Neuronas , Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/terapia , Neuronas/fisiología , Hipoxia/fisiopatología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/etiología , Cognición/fisiología , Estrés Oxidativo/fisiología , AnimalesRESUMEN
BACKGROUND: Penpulimab is a novel programmed death (PD)-1 inhibitor. This study aimed to establish the efficacy and safety of first line penpulimab plus chemotherapy for advanced squamous non-small-cell lung cancer. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial enrolled patients with locally advanced or metastatic squamous non-small-cell lung cancer from 74 hospitals in China. Eligible participants were aged 18-75 years, had histologically or cytologically confirmed locally advanced (stage IIIb or IIIc) or metastatic (stage IV) squamous non-small-cell lung cancer, were ineligible to complete surgical resection and concurrent or sequential chemoradiotherapy, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, did not have previous systemic chemotherapy for locally advanced or metastatic non-small-cell lung cancer, and had one or more measurable lesions according to RECIST (version 1.1). Participants were randomly assigned (1:1) to receive intravenous penpulimab 200 mg or placebo (excipient of penpulimab injection), plus paclitaxel 175 mg/m2 and carboplatin AUC of 5 intravenously on day 1 every 3 weeks for four cycles, followed by penpulimab or placebo as maintenance therapy. Stratification was done according to the PD-L1 tumour proportion score (<1% vs 1-49% vs ≥50%) and sex (male vs female). The participants, investigators, and other research staff were masked to group assignment. The primary outcome was progression-free survival assessed by the masked Independent Radiology Review Committee in the intention-to-treat population and patients with a PD-L1 tumour proportion score of 1% or more (PD-L1-positive subgroup). The primary analysis was based on the intention-to-treat analysis set (ie, all randomly assigned participants) and the PD-L1-positive subgroup. The safety analysis included all participants who received at least one dose of study drug after enrolment. This trial was registered with ClinicalTrials.gov (NCT03866993). FINDINGS: Between Dec 20, 2018, and Oct 10, 2020, 485 patients were screened, and 350 participants were randomly assigned (175 in the penpulimab group and 175 in the placebo group). Of 350 participants, 324 (93%) were male and 26 (7%) were female, and 347 (99%) were of Han ethnicity. In the final analysis (June 1, 2022; median follow-up, 24·7 months [IQR 0-41·4]), the penpulimab group showed an improved progression-free survival compared with the placebo group, both in the intention-to-treat population (median 7·6 months, 95% CI 6·8--9·6 vs 4·2 months, 95% CI 4·2-4·3; HR 0·43, 95% CI 0·33-0·56; p<0·0001) and in the PD-L1-positive subgroup (8·1 months, 5·7-9·7 vs 4·2 months, 4·1-4·3; HR 0·37, 0·27-0·52, p<0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 120 (69%) 173 patients in the penpulimab group and 119 (68%) of 175 in the placebo group. INTERPRETATION: Penpulimab plus chemotherapy significantly improved progression-free survival in patients with advanced squamous non-small-cell lung cancer compared with chemotherapy alone. The treatment was safe and tolerable. Penpulimab combined with paclitaxel and carboplatin is a new option for first-line treatment in patients with this advanced disease. FUNDING: The National Natural Science Foundation of China, Shanghai Municipal Health Commission, Chia Tai Tianqing Pharmaceutical, Akeso.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatino , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Paclitaxel , Humanos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Persona de Mediana Edad , Femenino , Método Doble Ciego , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , China , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Resultado del Tratamiento , Supervivencia sin ProgresiónRESUMEN
Abstract Objectives The prognosis of patients with Small Cell Lung Cancer (SCLC) can be predicted by their Lymph Node (LN) status. The authors aimed to assess the correlations between SCLC survival and number of LN Ratio (LNR), positive LN (pLNs), and Logarithmic Odds of positive LN (LODDS). Methods This cohort study retrospectively included 1,762 patients with SCLC from the SEER database 2004‒2015. The X-tile software was used to determine the cutoff values for pLNs, LNR, and LODDS. The correlations between pLNs, LNR, and LODDS with Overall Survival (OS) and Cancer-Specific Survival (CSS) were explored using Cox regression analysis. The study used the C-index to assess the predictive value of LNR, pLNs, and LODDS on survival. Results Among these 1,762 patients, 121 (6.87%) were alive, 1,641 (93.13%) died, and 1,532 (86.95%) died of SCLC. In univariable COX analysis, LNR, pLNs, and LODDS all showed a correlation with CSS and OS (p < 0.05). In multivariable COX analysis, only patients with LODDS (> 0.3 vs. ≤ 0.3) were related to both worse OS (HR = 1.28, 95% CI 1.10‒1.50) and CSS (HR = 1.29, 95% CI 1.10‒1.51), but no correction was observed between LNR and pLNs and survival (p > 0.05). The C-indices for predicting OS for LODDS were 0.552 (95% CI 0.541‒0.563), for LNR 0.504 (95% CI 0.501‒0.507), and for pLNs 0.527 (95% CI 0.514‒0.540). Moreover, the association between LODDS and prognosis in SCLC patients was significant only in patients with LN stage N1 and N2, but not in stage N3. Conclusion LODDS may be better than other LN assessment tools at predicting survival in SCLC patients.
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Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in sleep in which the airways narrow or collapse during sleep, causing obstructive sleep apnea. The prevalence of OSAS continues to rise worldwide, particularly in middle-aged and elderly individuals. The mechanism of upper airway collapse is incompletely understood but is associated with several factors, including obesity, craniofacial changes, altered muscle function in the upper airway, pharyngeal neuropathy, and fluid shifts to the neck. The main characteristics of OSAS are recurrent pauses in respiration, which lead to intermittent hypoxia (IH) and hypercapnia, accompanied by blood oxygen desaturation and arousal during sleep, which sharply increases the risk of several diseases. This paper first briefly describes the epidemiology, incidence, and pathophysiological mechanisms of OSAS. Next, the alterations in relevant signaling pathways induced by IH are systematically reviewed and discussed. For example, IH can induce gut microbiota (GM) dysbiosis, impair the intestinal barrier, and alter intestinal metabolites. These mechanisms ultimately lead to secondary oxidative stress, systemic inflammation, and sympathetic activation. We then summarize the effects of IH on disease pathogenesis, including cardiocerebrovascular disorders, neurological disorders, metabolic diseases, cancer, reproductive disorders, and COVID-19. Finally, different therapeutic strategies for OSAS caused by different causes are proposed. Multidisciplinary approaches and shared decision-making are necessary for the successful treatment of OSAS in the future, but more randomized controlled trials are needed for further evaluation to define what treatments are best for specific OSAS patients.
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COVID-19 , Apnea Obstructiva del Sueño , Anciano , Persona de Mediana Edad , Humanos , COVID-19/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/genética , Apnea Obstructiva del Sueño/terapia , Hipoxia , Obesidad , FaringeRESUMEN
In western medicine, obstructive sleep apnea hypopnea syndrome (OSAHS) is an increasingly serious public health hazard, which is exacerbated by the obesity epidemic and an aging population. Ancient medical literature of traditional Chinese medicine (TCM) also recorded OSAHS-like symptoms but described the disease from a completely distinct theoretical perspective. The earliest records of snoring in ancient China can be traced back 2500 years. In TCM, the pathogenesis of OSAHS can be attributed mainly to turbid phlegm and blood stasis. Various TCM prescriptions, herbal medicines, and external therapy have also been proposed for the prevention and therapy of OSAHS. Some of these strategies are still used in current clinical practice. This review highlights historical characterizations of OSAHS and the theory of TCM and also explores its therapy in TCM, which may shed light on future OSAHS research. This is the first systematic English review of the role of TCM in the treatment of OSAHS.
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Medicina Tradicional China , Apnea Obstructiva del Sueño , Humanos , Anciano , Polisomnografía , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/terapia , Síndrome , Frecuencia Respiratoria , Ronquido/epidemiología , Ronquido/terapiaRESUMEN
BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a global challenge since the December 2019. The hospital stay is one of the prognostic indicators, and its predicting model based on CT radiomics features is important for assessing the patients' clinical outcome. The study aimed to develop and test machine learning-based CT radiomics models for predicting hospital stay in patients with COVID-19 pneumonia. METHODS: This retrospective, multicenter study enrolled patients with laboratory-confirmed SARS-CoV-2 infection and their initial CT images from 5 designated hospitals in Ankang, Lishui, Lanzhou, Linxia, and Zhenjiang between January 23, 2020 and February 8, 2020. Patients were classified into short-term (≤10 days) and long-term hospital stay (>10 days). CT radiomics models based on logistic regression (LR) and random forest (RF) were developed on features from pneumonia lesions in first four centers. The predictive performance was evaluated in fifth center (test dataset) on lung lobe- and patients-level. RESULTS: A total of 52 patients were enrolled from designated hospitals. As of February 20, 21 patients remained in hospital or with non-findings in CT were excluded. Therefore, 31 patients with 72 lesion segments were included in analysis. The CT radiomics models based on 6 second-order features were effective in discriminating short- and long-term hospital stay in patients with COVID-19 pneumonia, with areas under the curves of 0.97 (95% CI, 0.83-1.0) and 0.92 (95% CI, 0.67-1.0) by LR and RF, respectively, in test. The LR and RF model showed a sensitivity and specificity of 1.0 and 0.89, 0.75 and 1.0 in test respectively. As of February 28, a prospective cohort of six discharged patients were all correctly recognized as long-term stay using RF and LR models. CONCLUSIONS: The machine learning-based CT radiomics features and models showed feasibility and accuracy for predicting hospital stay in patients with COVID-19 pneumonia.
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BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has outbreak in the world. Little is known about the clinical characteristics of patients with SARS-CoV-2 infection in the high-altitude region of China. We reported the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) in Gansu province, China. METHODS: In this retrospective study, patients with laboratory-confirmed SARS-CoV-2 infection were consecutively enrolled from January 21, 2020 to February 11, 2020. The information on the epidemiological, clinical characteristics, laboratory tests, radiological features on admission, treatment and outcome were obtained with the final follow-up of March 13, 2020. On the basis of the median length of hospital stay, patients were further analyzed in two groups (long- vs. short-hospital stay). RESULTS: Of the 86 patients of COVID-19 in 11 cities of Gansu Province, the median hospital stay was 14.0 days (interquartile rang, 11.0-19.0 days). In the overall cohort, the median age was 41.0 years (interquartile rang, 31.0-54.3 years), and 48 (55.8%) patients were female. Forty (46.5%) had a history of exposure to epidemic regions, but none exposed to the Huanan seafood market in Wuhan. Common symptoms included fever (41, 47.7%), and cough (37, 43.0%). On admission, 30 (34.9%) and 58 (67.4%) patients had leukopenia and lymphopenia. According to chest CT scans, 53 (66.3%) of 80 patients showed bilateral pneumonia, and 19 (23.8%) of 80 patients showed unilateral pneumonia. Of the 15 asymptomatic cases, 10 (66.6%) cases were found CT findings of pneumonia. Besides, there were 65 (75.6%) patients with mild and moderate type of COVID-19. All 86 patients received antiviral and traditional Chinese medicine therapy, 53 (61.6%) received antibacterial therapy, and 3 (3.5%) patients received invasive ventilator mechanical ventilation. The proportion of patients received antibiotic treatment in long-hospital stay group was significantly higher than that in the short-hospital stay group (P=0.045). As of March 13, 2020, 84 (97.7%) patients were discharged, and two (2.3%) cases died. CONCLUSIONS: In the Gansu province cohort of 86 patients of COVID-19, most patients were with mild or moderate type, and most asymptomatic cases showed CT imaging findings of SARS-CoV-2 related pneumonia.
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Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/terapia , Neumonía Viral/diagnóstico , Neumonía Viral/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus/aislamiento & purificación , COVID-19 , Niño , Preescolar , China/epidemiología , Infecciones por Coronavirus/epidemiología , Femenino , Humanos , Lactante , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Resultado del Tratamiento , Adulto JovenAsunto(s)
Infecciones por Coronavirus , Coronavirus , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , China , Humanos , Hígado , SARS-CoV-2RESUMEN
Ginkgo leaf extract and dipyridamole injection (GLED), a kind of Chinese herbal medicine preparation, has been considered as a promising supplementary treatment for chronic cor pulmonale (CCP). Although an analysis of the published literature has been performed, the exact effects and safety of GLED have yet to be systematically investigated. Therefore, a wide-ranging systematic search of electronic databases from which to draw conclusions was conducted. All randomized controlled trials concerning the GLED plus conventional treatments for CCP were selected in the present study. Main outcomes were treatment efficacy, blood gas and hemorrheology indexes, and adverse events. Data from 28 trials with 2457 CCP patients were analyzed. The results indicated that, compared with conventional treatments alone, the combination of conventional treatments with GLED obviously improved the markedly effective rate (RR = 1.44, 95% CI = 1.31-1.58, P < 0.00001) and total effective rate (RR = 1.28, 95% CI = 1.18-1.38, P < 0.00001). Moreover, the hemorrheology (PaO2, P < 0.00001; PaCO2, P < 0.00001; SaO2, P < 0.00001; pH value, P = 0.05) and blood gas indexes (PV, WBHSV, WBMSV, WBLSV, hematocrit and FBG, P < 0.01) of CCP patients were also significantly ameliorated after the combined therapy. The frequency of adverse events did not differ significantly between the two groups (P > 0.05). In summary, evidence from the meta-analysis suggested that the combination of conventional treatments and GLED appeared to be effective and relatively safe for CCP. Therefore, GLED mediated therapy could be recommended as an adjuvant treatment for CCP.
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Dipiridamol/farmacología , Extractos Vegetales/farmacología , Enfermedad Cardiopulmonar/tratamiento farmacológico , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedad Crónica , Dipiridamol/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Ginkgo biloba/metabolismo , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Extractos Vegetales/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
[This corrects the article DOI: 10.1155/2016/9782031.].
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In the present study, an attempt was made to determine whether administration of fucoxanthin could attenuate cerebral ischemic/reperfusion (I/R) injury and its possible mechanisms using an in vivo middle cerebral artery occlusion (MCAO) model and an in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) model. Fucoxanthin was intragastrically administrated in different doses (30 mg/kg, 60 mg/kg, and 90 mg/kg, respectively) to the rats 1 h before MCAO induction. The neurological function, infarct area and brain water content of rats were then evaluated. Rat cortical neuron were pretreated with different doses of fucoxanthin (5 µM, 10 µM, and 20 µM) and then subjected to OGD/R. Expression levels of proteins in the brain tissues and cultured cells were determined by western blotting. Our results demonstrated that fucoxanthin pretreatment improved the neurologic deficit score, lowered the infarct volume and reduced the expression of apoptosis-associated proteins in brain tissues. In addition, fucoxanthin also suppresses OGD/R-induced apoptosis and ROS accumulation in cultured neurons. Furthermore, we found that fucoxanthin could significantly activate the Nrf2/HO-1 signaling through inducing Nrf2 nuclear translocation with enhanced HO-1 expression, and Nrf2 knockdown obviously abrogated the beneficial role of fucoxanthin in OGD/R-treated neurons. These findings suggested that fucoxanthin could be exploited as a therapeutic target for protecting neurons from cerebral I/R injury.
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Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Hemo Oxigenasa (Desciclizante)/metabolismo , Infarto de la Arteria Cerebral Media/prevención & control , Factor 2 Relacionado con NF-E2/metabolismo , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/prevención & control , Xantófilas/farmacología , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Encéfalo/enzimología , Encéfalo/patología , Encéfalo/fisiopatología , Células Cultivadas , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Infarto de la Arteria Cerebral Media/enzimología , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/fisiopatología , Masculino , Factor 2 Relacionado con NF-E2/genética , Neuronas/enzimología , Neuronas/patología , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/enzimología , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
The present study aimed to explore whether deregulated miR-138 is implicated in cerebral I/R injury-impaired learning and memory abilities. Rats were subjected to bilateral common carotid occlusion followed by reperfusion to induce cerebral I/R injury. A model of oxygen-glucose deprivation and reperfusion (OGD/R) was conducted to mimic cerebral I/R conditions in vitro. MiR-138 expression levels were reduced in the hippocampus of cerebral I/R injured rats. Inhibition of miR-138 ameliorated the impaired learning and memory abilities of rats, and promoted autophagy and thus attenuated apoptosis in the OGD/R-treated hippocampal neurons. Moreover, miR-138 targets the 3'-UTR of SIRT1 and repressed its expression. These results showed that miR-138 could improve the learning and memory abilities via promoting autophagy under cerebral I/R injured conditions.
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Isquemia Encefálica/genética , MicroARNs/metabolismo , Daño por Reperfusión/genética , Sirtuina 1/genética , Animales , Autofagia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Hipocampo/metabolismo , Masculino , Memoria , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Aprendizaje EspacialRESUMEN
The survival of non-small cell lung cancer (NSCLC) is poor due to high metastasis, and the indispensable step of metastasis includes epithelial-mesenchymal transition (EMT). In the study, by analyzing the dataset of the Cancer Genome Atlas (TCGA), we found that the expression of Canopy homolog 2 (CNPY2) is increased both in adenocarcinoma and squamous cell carcinoma, which is further confirmed in NSCLC tissues. Not only that, there is a negative correlation between CNPY2 and E-cadherin expression at mRNA level. Wound healing and transwell matrix penetration assay showed that overexpression of CNPY2 promotes the capability for invasion and metastasis of NSCLC cells. Further analysis uncovered that overexpression of CNPY2 can activate the AKT/GSK3ß pathway, which leads to the inactivation of GSK-3ß. The inactivation of GSK-3ß increases the level of Snail, and then decreases the expression of E-cadherin to promote EMT. Eventually, inhibition of AKT suppresses the malignant transformation of CNPY2-upregulated cells. The above results suggest that CNPY2 may be served as a novel therapeutic target to therapy the NSCLC.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/genética , Cadherinas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Factores de Transcripción de la Familia Snail/metabolismoRESUMEN
BACKGROUND: This study aimed to investigate the effect of bone marrow derived mesenchymal stem cells (rBMSCs) transduced with lentiviral vectors expressing endothelial nitric oxide synthase (eNOS) and/or a mutant caveolin-1(F92A-Cav1), on the pulmonary haemodynamics and structure in a rat model of pulmonary arterial hypertension (PAH). METHODS: Pulmonary arterial hypertension was induced with monocrotaline (MCT) in 60 adult male Wistar rats prior to delivery of lentiviral vector transduced rBMSCs expressing Cav1, eNOS and/or F92A-Cav1. Changes in pulmonary haemodynamics, right ventricular hypertrophy index (RVHI), and serum nitric oxide (NO) were evaluated. Ultrastructure changes in lung tissues were observed by transmission electron microscopy. Expression of Kruppel-like factor 4 (KLF4), p53, P21, eNOS, and alpha-smooth muscle actin were evaluated by real time PCR, western blotting or immunohistochemistry. RESULTS: Treatment of PAH rats with gene modified rBMSCs (eNOS +/- Cav1 F92A) decreased right ventricular systolic pressure and improved pulmonary haemodynamics. The protein of alpha-smooth muscle actin expression was decreased whilst KLF4, p53, P21, eNOS expression, and serum NO concentration was elevated. The survival rate of rats in the treatment groups was also improved, after 35 days of observation. CONCLUSION: Intravenous delivery of rBMSCs expressing eNOS/F92A-Cav1 to PAH rats inhibits pulmonary vascular smooth muscle cell proliferation, and improves pulmonary haemodynamics, vascular remodelling and short-term survival. Activation of KLF4-p53 signalling pathway may be involved in these beneficial effects.
Asunto(s)
Caveolina 1/biosíntesis , Proliferación Celular , Regulación de la Expresión Génica , Hipertensión Pulmonar , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Músculo Liso Vascular/metabolismo , Mutación Missense , Miocitos del Músculo Liso/metabolismo , Óxido Nítrico Sintasa de Tipo III/biosíntesis , Aloinjertos , Sustitución de Aminoácidos , Animales , Caveolina 1/genética , Modelos Animales de Enfermedad , Humanos , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/terapia , Factor 4 Similar a Kruppel , Masculino , Óxido Nítrico Sintasa de Tipo III/genética , Ratas , Ratas Wistar , Transducción GenéticaRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with sustained vasoconstriction, inflammation and suppressed apoptosis of smooth muscle cells. Our previous studies have found that rat bone marrow-derived mesenchymal stem cells (rBMSCs) transduced with a mutant caveolin-1(F92A-Cav1) could enhance endothelial nitric oxide synthase (eNOS) activity and improve pulmonary vascular remodeling, but the potential mechanism is not yet fully explored. The present study was to investigate the gene expression profile upon rBMSCs/F92A-Cav1delivered to PAH rat to evaluate the role of F92A-Cav1 in its regulation. METHODS: PAH was induced with monocrotaline (MCT, 60mg/kg) prior to delivery of lentiviral vector transduced rBMSCs expressing Cav1 or F92A-Cav1. Gene expression profiling was performed using Rat Signal Transduction PathwayFinder array. The expression changes of 84 key genes representing 10 signal transduction pathways in rat following rBMSCs/F92A-Cav1 treatment was examined. RESULTS: Screening with the Rat Signal Transduction PathwayFinder R2 PCR Array system and subsequent western blot, immunohistochemistry or real time PCR analysis revealed that F92A-Cav1 modified rBMSCs can inhibit the inflammation factors (TNF-alpha, Icam1 and C/EBPdelta), pro-proliferation genes (c-Myc, Bcl2a1d, Notch1and Hey2), oxidative stress gene (Hmox1) and activate cell cycle arrested gene Cdkn1a, ameliorating inflammation and inhibiting cell proliferation in PAH rat. CONCLUSION: rBMSCs/F92A-Cav1 inhibits inflammation and cell proliferation by regulating signaling pathways that related to inflammation, proliferation, cell cycle and oxidative stress.