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1.
Commun Biol ; 7(1): 545, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714724

RESUMEN

CircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a ß-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4-ß-catenin transcription complex through competitive to ß-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/ß-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing ß-catenin signaling may serve as a potential therapeutic candidate.


Asunto(s)
Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Células Madre Neoplásicas , ARN Circular , Factor de Transcripción SOX9 , Neoplasias Gástricas , Factor de Transcripción 4 , beta Catenina , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Humanos , Factor de Transcripción SOX9/metabolismo , Factor de Transcripción SOX9/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , beta Catenina/metabolismo , beta Catenina/genética , ARN Circular/genética , ARN Circular/metabolismo , Factor de Transcripción 4/genética , Factor de Transcripción 4/metabolismo , Animales , Ratones , Línea Celular Tumoral , Ratones Desnudos , Masculino , Femenino , Resistencia a Antineoplásicos/genética , Ratones Endogámicos BALB C , Persona de Mediana Edad
2.
J Craniofac Surg ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38687036

RESUMEN

OBJECTIVE: Report on a case of pseudoaneurysm which was caused by injury of the internal carotid artery (ICA) during endoscopic endonasal surgery (EES), which was followed by rebleeding after treatment with a Willis covered stent. METHODS: A woman, aged 68, underwent EES for the treatment of a pituitary adenoma. During the surgery, the right ICA was injured, and successfully hemostasis by packed with cottonoid and gelatin sponge. Besides, cerebral angiography was performed in the interventional operating room for the purpose of discovering the formation of a pseudoaneurysm in the cavernous sinus segment of ICA, which was treated with a covered stent. After successfully placing the covered stent, the patient was promptly transferred to the general operating room for the removal of the cottonoid and to address the bleeding once again. The authors employ crushed muscles and cottonoid to locally compress and stop bleeding. Owing to concerns about the risk of rebleeding in the patient, after stent implantation, the patient did not utilize antiplatelet drugs. After the surgery, the patient developed occlusion of the right ICA and massive cerebral infarction in the right hemisphere. Dehydration, anti-infection, rehabilitation, hyperbaric oxygen, as well as related treatments, were given. The cottonoid was removed in EES 2 months postsurgery, and no instances of bleeding were observed. Six months after surgery, the patient had clear consciousness and hemiplegia in the left limb, with a Glasgow Outcome Scale score of 4. RESULTS: The ICA was injured during EES, which resulted in the formation of a pseudoaneurysm, the Willis stent was adopted for treatment, and there was a risk of rebleeding after the nasal packing (cottonoid, crushed muscles) was removed immediately. CONCLUSIONS: The ICA was injured during EES after bleeding was controlled by packing with cottonoid, crushed muscles, etc, subsequently, the patient was given intravascular treatment, it is advised to make thorough preparations and, after a suitable period, remove nasal packing in the hybrid operating room to address unexpected situations and unforeseen circumstances.

3.
Int Immunopharmacol ; 132: 111946, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38552292

RESUMEN

Ensuring the homeostatic integrity of pulmonary artery endothelial cells (PAECs) is essential for combatting pulmonary arterial hypertension (PAH), as it equips the cells to withstand microenvironmental challenges. Spermidine (SPD), a potent facilitator of autophagy, has been identified as a significant contributor to PAECs function and survival. Despite SPD's observed benefits, a comprehensive understanding of its protective mechanisms has remained elusive. Through an integrated approach combining metabolomics and molecular biology, this study uncovers the molecular pathways employed by SPD in mitigating PAH induced by monocrotaline (MCT) in a Sprague-Dawley rat model. The study demonstrates that SPD administration (5 mg/kg/day) significantly corrects right ventricular impairment and pathological changes in pulmonary tissues following MCT exposure (60 mg/kg). Metabolomic profiling identified a purine metabolism disorder in MCT-treated rats, which SPD effectively normalized, conferring a protective effect against PAH progression. Subsequent in vitro analysis showed that SPD (0.8 mM) reduces oxidative stress and apoptosis in PAECs challenged with Dehydromonocrotaline (MCTP, 50 µM), likely by downregulating purine nucleoside phosphorylase (PNP) and modulating polyamine biosynthesis through alterations in S-adenosylmethionine decarboxylase (AMD1) expression and the subsequent production of decarboxylated S-adenosylmethionine (dcSAM). These findings advocate SPD's dual inhibitory effect on PNP and AMD1 as a novel strategy to conserve cellular ATP and alleviate oxidative injuries, thus providing a foundation for SPD's potential therapeutic application in PAH treatment.


Asunto(s)
Células Endoteliales , Monocrotalina , Poliaminas , Hipertensión Arterial Pulmonar , Arteria Pulmonar , Purinas , Ratas Sprague-Dawley , Espermidina , Remodelación Vascular , Animales , Espermidina/farmacología , Espermidina/uso terapéutico , Purinas/farmacología , Poliaminas/metabolismo , Masculino , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Remodelación Vascular/efectos de los fármacos , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Ratas , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Hipertensión Arterial Pulmonar/inducido químicamente , Hipertensión Arterial Pulmonar/metabolismo , Células Cultivadas , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Purina-Nucleósido Fosforilasa/metabolismo , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/metabolismo , Adenosilmetionina Descarboxilasa/metabolismo , Modelos Animales de Enfermedad , Humanos
4.
J Craniofac Surg ; 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38363289

RESUMEN

BACKGROUND: Sylvian aqueduct syndrome is a rare complication after ventriculoperitoneal (V-P) shunt surgery and is not easily diagnosed. METHODS: A 26-year-old male with obstructive hydrocephalus due to tectal glioma was treated with a V-P shunt surgery in another hospital. After the surgery, the patient developed an intractable disturbance of consciousness. When the V-P shunt pressure was raised or lowered, the patient's consciousness disorder still could not be improved. The patient was diagnosed with Sylvian aqueduct syndrome, a rare complication after V-P shunt operation. RESULTS: The paper clarifies the treatment experience with simultaneous endoscopic third ventriculostomy (ETV) and tectum gliomas biopsy, postoperative pathology suggestive of fibrillary astrocytoma; after surgery, the Sylvian aqueduct syndrome was cured and the patient recovered well. CONCLUSIONS: The preferred treatment for obstructive hydrocephalus caused by tumors in the Pineal region is the ETV operation. If an ETV operation and biopsy operation are performed simultaneously, more details need to be noted.

5.
Drug Des Devel Ther ; 18: 475-491, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38405578

RESUMEN

Purpose: The underlying causes of pulmonary arterial hypertension (PAH) often remain obscure. Addressing PAH with effective treatments presents a formidable challenge. Studies have shown that Hydroxysafflor yellow A (HSYA) has a potential role in PAH, While the mechanism underlies its protective role is still unclear. The study was conducted to investigate the potential mechanisms of the protective effects of HSYA. Methods: Using databases such as PharmMapper and GeneCards, we identified active components of HSYA and associated PAH targets, pinpointed intersecting genes, and constructed a protein-protein interaction (PPI) network. Core targets were singled out using Cytoscape for the development of a model illustrating drug-component-target-disease interactions. Intersection targets underwent analysis for Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Selected components were then modeled for target interaction using Autodock and Pymol. In vivo validation in a monocrotaline-induced PAH (MCT-PAH) animal model was utilized to substantiate the predictions made by network pharmacology. Results: We associated HSYA with 113 targets, and PAH with 1737 targets, identifying 34 mutual targets for treatment by HSYA. HSYA predominantly affects 9 core targets. Molecular docking unveiled hydrogen bond interactions between HSYA and several PAH-related proteins such as ANXA5, EGFR, SRC, PPARG, PGR, and ESR1. Conclusion: Utilizing network pharmacology and molecular docking approaches, we investigated potential targets and relevant human disease pathways implicating HSYA in PAH therapy, such as the chemical carcinogenesis receptor activation pathway and the cancer pathway. Our findings were corroborated by the efficacious use of HSYA in an MCT-induced rat PAH model, confirming its therapeutic potential.


Asunto(s)
Chalcona , Chalcona/análogos & derivados , Medicamentos Herbarios Chinos , Hipertensión Arterial Pulmonar , Quinonas , Humanos , Animales , Ratas , Hipertensión Arterial Pulmonar/inducido químicamente , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Remodelación Vascular , Simulación del Acoplamiento Molecular , Chalcona/farmacología
6.
Eur J Pharmacol ; 965: 176315, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38176636

RESUMEN

Pulmonary arterial hypertension (PAH) is a complex and fatal cardio-pulmonary vascular disease. Decompensated right ventricular hypertrophy (RVH) caused by cardiomyocyte hypertrophy often leads to fatal heart failure, the leading cause of mortality among patients. Sodium butyrate (SB), a compound known to reduce cardiac hypertrophy, was examined for its potential effect and the underlying mechanism of SB on PAH-RVH. The in vivo study showed that SB alleviated RVH and cardiac dysfunction, as well as improved life span and survival rate in MCT-PAH rats. The in vivo and in vitro experiments showed that SB could attenuate cardiomyocyte hypertrophy by reversing the expressions of H19, let-7g-5p, insulin-like growth factor 1 receptor (IGF1 receptor), and pERK. H19 inhibition restored the level of let-7g-5p and prevented the overexpression of IGF1 receptor and pERK in hypertrophic cardiomyocytes. In addition, dual luciferase assay revealed that H19 demonstrated significant binding with let-7g-5p, acting as its endogenous RNA. Briefly, SB attenuated PAH-RVH by inhibiting the H19 overexpression, restoring the level of let-7g-5p, and hindering IGF1 receptor/ERK activation.


Asunto(s)
Hipertensión Pulmonar , MicroARNs , Hipertensión Arterial Pulmonar , Humanos , Ratas , Animales , Hipertrofia Ventricular Derecha , Hipertensión Arterial Pulmonar/complicaciones , Ácido Butírico/farmacología , Ácido Butírico/uso terapéutico , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar Primaria Familiar , MicroARNs/genética , MicroARNs/metabolismo , Factor I del Crecimiento Similar a la Insulina
7.
Cancer Cell Int ; 23(1): 286, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37990321

RESUMEN

BACKGROUND: Chemoresistance is a major clinical challenge that leads to tumor metastasis and poor clinical outcome. The mechanisms underlying gastric cancer resistance to chemotherapy are still unclear. METHODS: We conducted bioinformatics analyses of publicly available patient datasets to establish an apoptotic phenotype and determine the key pathways and clinical significance. In vitro cell models, in vivo mouse models, and numerous molecular assays, including western blotting, qRT-PCR, immunohistochemical staining, and coimmunoprecipitation assays were used to clarify the role of factors related to apoptosis in gastric cancer in this study. Differences between datasets were analyzed using the Student's t-test and two-way ANOVA; survival rates were estimated based on Kaplan-Meier analysis; and univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors. RESULTS: Bulk transcriptomic analysis of gastric cancer samples established an apoptotic phenotype. Proapoptotic tumors were enriched for DNA repair and immune inflammatory signaling and associated with improved prognosis and chemotherapeutic benefits. Functionally, cyclin-dependent kinase 5 (CDK5) promoted apoptosis of gastric cancer cells and sensitized cells and mice to oxaliplatin. Mechanistically, we demonstrate that CDK5 stabilizes DP1 through direct binding to DP1 and subsequent activation of E2F1 signaling. Clinicopathological analysis indicated that CDK5 depletion correlated with poor prognosis and chemoresistance in human gastric tumors. CONCLUSION: Our findings reveal that CDK5 promotes cell apoptosis by stabilizing DP1 and activating E2F1 signaling, suggesting its potential role in the prognosis and therapeutic decisions for patients with gastric cancer.

8.
Eur J Pharmacol ; 959: 176077, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37820784

RESUMEN

Pulmonary artery smooth muscle cells (PASMCs) phenotypic switching and pulmonary artery endothelial cells (PAECs) endothelial-mesenchymal transition (EndMT) are important in promoting pulmonary hypertension (PH)-pulmonary vascular remodeling (PVR). Resveratrol can efficiently inhibit the proliferation of PASMCs, but its application is limited due to its low bioavailability and solubility. In this study, we modified resveratrol to assess the role of A ring N(CH3)2-based derivatives of resveratrol (Res4) in PVR-PASMCs phenotypic switching and PVR-PAECs EndMT. Chemical methods were used for the preparation of Res4; NMRS and HPLC were used to authenticate Res4. Mice developed PVR after 4 weeks of hypoxia (10% O2). Res4 (50 mg/kg/d) attenuated right ventricular systolic pressure, right ventricular hypertrophy, and PVR. PASMCs developed phenotypic switching and PAECs developed EndMT after 2 days of hypoxia (3% O2). Res4 (10 µM) could inhibit PASMCs and PAECs viability. Res4 could decrease proliferating cell nuclear antigen (PCNA) and osteopontin (OPN) expression, and increase α-smooth muscle actin (α-SMA) and vimentin expression in PASMCs. It could also decrease PCNA, α-SMA, vimentin expression and increase platelet endothelial cell adhesion molecule (CD31) expression in PAECs. Notably, Res4 inhibited the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated protein kinase (ERK), Jun-N-terminal kinase (JNK), and p38 kinase in hypoxia-treated PASMCs and PAECs, indicating MAPK pathway may be involved in Res4-induced inhibition of PASMCs phenotypic switching and PAECs EndMT. Our data demonstrated that Res4 exerts antiproliferative effects by regulating PASMCs phenotypic switching and PAECs EndMT. Res4 may be potentially used as a drug against PH-PVR.


Asunto(s)
Hipertensión Pulmonar , Ratones , Animales , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Resveratrol/farmacología , Resveratrol/metabolismo , Vimentina/metabolismo , Células Endoteliales/metabolismo , Remodelación Vascular , Hipoxia/complicaciones , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Arteria Pulmonar , Miocitos del Músculo Liso , Proliferación Celular , Células Cultivadas
9.
BMC Musculoskelet Disord ; 24(1): 364, 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37161368

RESUMEN

BACKGROUND: Currently, there is no consensus on the most appropriate technique for obtaining lateral hip radiographs after cephalomedullary nail (CMN) surgery. The aim of this study was to investigate the distribution of two commonly used postoperative lateral hip radiographic methods (classic lateral view and modified lateral view) and try to find out which one is better suited for this situation. METHODS: A retrospective analysis was conducted on 146 patients who underwent surgical fixation for extracapsular hip fractures between January 2018 and June 2022. The main outcome measured was the angle between the straight part of the CMN and the lag screw/blade on hip lateral X-rays (CMNA). The lateral hip radiographs were categorized into two groups based on different lateral hip radiographic methods. CMNA, patient age, gender, fracture classification based on the 2018 AO classification, nail length (short/long), surgical side (left/right), height, weight, BMI, preoperative waiting time, postoperative imaging interval were collected and compared between the two groups. RESULTS: The distribution trend of CMNA significantly differs between two types of hip joint lateral radiographic methods. Specifically, the classic lateral method exhibits a significantly bimodal and skewed distribution with a median (p25, p75) of -21.6° (-31.2°, -8°), whereas the modified lateral method presents a normal distribution with a mean ± SD of +7.57° ± 14.4°. The difference in the Mean Rank between the classic (47.10) and the modified (102.96) lateral methods is statistically significant (P < 0.001). CONCLUSIONS: The CMNA method is an excellent tool for studying the lateral distribution.We recommend using the modified lateral view as the preferred option for obtaining lateral hip radiographs after CMN surgery due to its superior distribution of CMNA and greater patient-friendliness.


Asunto(s)
Tornillos Óseos , Fracturas de Cadera , Humanos , Estudios Retrospectivos , Radiografía , Cuidados Posoperatorios , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía
11.
World J Pediatr ; 19(10): 972-982, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37029331

RESUMEN

BACKGROUND: Previous studies have linked gestational diabetes (GDM) with allergies in offspring. However, the effect of specific glucose metabolism metrics was not well characterized, and the role of polyunsaturated fatty acids (PUFAs), a modifier of metabolism and the immune system, was understudied. We aimed to investigate the association between maternal GDM and allergic diseases in children and the interaction between glucose metabolism and PUFAs on allergic outcomes. METHODS: This prospective cohort study included 706 mother-child dyads from Guangzhou, China. Maternal GDM was diagnosed via a 75-g oral glucose tolerance test (OGTT), and dietary PUFAs were assessed using a validated food frequency questionnaire. Allergic disease diagnoses and the age of onset were obtained from medical records of children within three years old. RESULTS: Approximately 19.4% of women had GDM, and 51.3% of children had any allergic diseases. GDM was positively associated with any allergic diseases (hazard ratio [HR] 1.40; 95% confidence interval (CI) 1.05-1.88) and eczema (HR 1.44; 95% CI 1.02-1.97). A unit increase in OGTT after two hours (OGTT-2 h) glucose was associated with an 11% (95% CI 2%-21%) higher risk of any allergic diseases and a 17% (95% CI 1-36%) higher risk of food allergy. The positive associations between OGTT-2 h glucose and any allergic diseases were strengthened with decreased dietary a-linolenic acid (ALA) and increased n-6 PUFAs, linoleic acid (LA), LA/ALA ratio, and n-6/n-3 PUFA ratio. CONCLUSIONS: Maternal GDM was adversely associated with early-life allergic diseases, especially eczema. We were the first to identify OGTT-2 h glucose to be more sensitive in inducing allergy risk and that dietary PUFAs might modify the associations.


Asunto(s)
Diabetes Gestacional , Eccema , Hipersensibilidad , Embarazo , Femenino , Humanos , Preescolar , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiología , Estudios de Cohortes , Estudios Prospectivos , Hipersensibilidad/epidemiología , Glucosa
12.
Arch Physiol Biochem ; : 1-10, 2022 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-35867533

RESUMEN

Objective: This study aimed to investigate the functions of lncRNA H19 on glomerular endothelial structural damage of diabetic nephropathy (DN).Materials and Methods: Rats were fed a high sugar and fat high feed die, and intraperitoneally administrated with streptozotocin (30 mg/kg) to induce DN model. Meanwile, rat glomerular endothelial cells (rGEnCs) were treated with high a level of glucose (HG, 30 mM glucose)to induce structural damage.Results: Our results showed that H19 level was drastically increased in diabetic glomeruli and high-glucose (HG)-stimulated rat glomerular endothelial cells (rGEnCs). Deficiency of H19 ameliorated microalbumin, creatinine, BUN, and histopathological alterations in diabetic rats. In addition, H19 deficiency significantly attenuated the damage of endothelial structure by upregulating the expression of junction proteins ZO-1 and Occludin, glycolcalyx protein Syndecan-1, and endothelial activation marker sVCAM-1 and sICAM-1 in diabetic rats. The in vitro results also showed that H19-siRNA alleviated glycocalyx shedding, tight junctions damage, and endothelial activation in HG-stimulated rGEnCs. Moreover, H19 deficiency significantly enhanced the expression of p-Akt and p-eNOS and NO concentration in vitro and in vivo. Pre-treatment with Akt inhibitor LY294002 abrogated these favourable effects mediated by H19 deficiency.Discussion and Conclusion: These results indicate that H19 deficiency could mitigate the structural damage of glomerular endothelium in DN via activating Akt/eNOS pathway.

13.
Taiwan J Obstet Gynecol ; 61(3): 551-554, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35595457

RESUMEN

OBJECTIVE: Advanced maternal age and decreased ovarian reserve have been challenges for assisted reproductive technology (ART). Few cases, using autologous oocytes more than 46-years-old, have previously been reported. We seek to show how the age at which autologous oocytes may successfully be employed may be increasing. CASE REPORT: We report a 47-year-old woman with an anti-Müllerian hormone (AMH) level of 0.24 ng/mL, conceived through in vitro fertilization (IVF) using autologous oocytes. Patient was given an antagonist protocol for ovarian stimulation and one frozen-thawed embryo was transferred. The patient became pregnant. The course of her pregnancy was uneventful and she gave birth to a 3330 gm male baby by cesarean section. CONCLUSION: Technological advances permit women, who previously would have been considered too old to employ an autologous oocyte, to have a successful pregnancy with a live birth.


Asunto(s)
Nacimiento Vivo , Recuperación del Oocito , Cesárea , Transferencia de Embrión/efectos adversos , Transferencia de Embrión/métodos , Femenino , Fertilización In Vitro/efectos adversos , Fertilización In Vitro/métodos , Humanos , Masculino , Recuperación del Oocito/efectos adversos , Oocitos , Embarazo , Estudios Retrospectivos
14.
J Cell Mol Med ; 26(2): 422-435, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34913237

RESUMEN

Chemoresistance and migration represent major obstacles in the therapy of non-small-cell lung cancer (NSCLC), which accounts for approximately 85% of lung cancer patients in clinic. In the present study, we report that the compound C1632 is preferentially distributed in the lung after oral administration in vivo with high bioavailability and limited inhibitory effects on CYP450 isoenzymes. We found that C1632 could simultaneously inhibit the expression of LIN28 and block FGFR1 signalling transduction in NSCLC A549 and A549R cells, resulting in significant decreases in the phosphorylation of focal adhesion kinase and the expression of matrix metalloproteinase-9. Consequently, C1632 effectively inhibited the migration and invasion of A549 and A549R cells. Meanwhile, C1632 significantly suppressed the cell viability and the colony formation of A549 and A549R cells by inhibiting DNA replication and inducing G0/G1 cell cycle arrest. Interestingly, compared with A549 cells, C1632 possesses the same or even better anti-migration and anti-proliferation effects on A549R cells, regardless of drug resistance. In addition, C1632 also displayed the capacity to inhibit the growth of A549R xenograft tumours in mice. Altogether, these findings reveal the potential of C1632 as a promising anti-NSCLC agent, especially for chemotherapy-resistant NSCLC treatment.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Células A549 , Animales , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones , Proteínas de Unión al ARN/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal
15.
Chin Med ; 16(1): 136, 2021 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-34903262

RESUMEN

BACKGROUND: Vascular cognitive dysfunction in patients with vascular dementia (VD) is a kind of severe cognitive dysfunction syndrome caused by cerebrovascular diseases. At present, effective drugs to improve the cognitive function of VD patients still need to be explored. Transient Receptor Potential Melastatin 2 (TRPM2) channel is a nonspecific cation channel that plays a key role in the toxic death of neurons. Perillaldehyde (PAE) has the protective effect of epilepsy and insomnia and other central nervous system diseases. The aim of this study is to explore whether PAE improves cognitive function in VD rats and to investigate the potential mechanisms in vivo and vitro. METHODS: VD rats were induced by bilateral common carotid arteries occlusion (2-vessel occlusion [2VO]) and treated with PAE for 4 weeks. The neuroprotective effects of PAE was subsequently assessed by the Morris water maze, hematoxylin-eosin (HE) staining, Golgi staining, electron microscopy, Neuron-specific nuclear protein (Neu N) staining, and TdT-mediated dUTP nick end labeling (TUNEL) staining. After primary hippocampal neurons were isolated, cell viability was detected by MTT assay and intracellular Ca2+ concentration was detected by calcium imaging assay. The content of Nitriteoxide (NO), Malondialdehyde (MDA) and Superoxide dismutase (SOD) activity in serum of rats were observed by Enzyme Linked Immunosorbent Assay (ELISA). Immunohistochemistry, Western blot, and Confocal laser scanning were used to detect the expression levels of N-methyl-D-asprtate receptor-2B (NR2B) and TRPM2. RESULTS: The results showed that PAE can improve the number and activity of neurons, increase the length and number of dendrites in hippocampus, decrease the Vv value and PE value of neuronal nucleus and mitochondrial structure significantly, increase the s value and L value in nucleus structure, decrease the s value and L value in mitochondrial structure, and improve the learning and memory ability of rats significantly. And PAE can strengthen the ability of antioxidant stress confirmed by increasing the activity of SOD and reducing the production of MDA. The results of western blot, immunohistochemistry and immunofluorescence showed that PAE could reduce the level of TRPM2 and increase the expression of NR2B. CONCLUSIONS: Taken together, our findings provide evidence that the neuroprotective effects of PAE in VD rats maybe through TRPM2 inhibition and subsequent activation of NMDAR signaling pathway.

16.
Brain Behav ; 10(9): e01732, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32767660

RESUMEN

PURPOSE: High-resolution magnetic resonance imaging (HR-MRI) has high spatial resolution and can simultaneously perform wall and lumen imaging. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can evaluate the integrity of the blood-brain barrier. In this paper, the result of 3.0T HR-MRI and 3.0T DCE-MRI has been evaluated to explore the application value of unilateral middle cerebral artery inflammatory stenosis and changes in vascular permeability parameters of stroke events. METHODS: Thirty-six cases of neurological suspicion of central nervous system vasculitis of our hospital were selected from 20 January 2018 to 1 January 2019, who were diagnosed as unilateral middle cerebral artery M1 stenosis/occlusion by 3D TOF MRA. 3.0T HR-MRI and 3.0T DCE-MRI has been applied. RESULTS: Among the 36 patients who met the inclusion criteria, 23 patients with central nervous system vasculitis were diagnosed. The 23 patients with HR-MRI showed diffuse thickening and enhanced stenosis. The Ktrans value of 10/23 patients with acute-subacute cerebral infarction and 3/23 patients in chronic phase were significantly higher than that of the mirror side, and the Ktrans value of these patients remeasured in the same region of interest is lower than before after 6 months treatment. The Ktrans value in the target area of 10 patients without cerebrovascular events was not statistically significant compared with the mirror side. The Ktrans value of patients with acute-subacute cerebral infarction was significantly higher than that without cerebrovascular events (0.098 ± 0.038 vs. 0.007 ± 0.001, p = .000), and there was no significant difference between Ktrans in the chronic infarction group and the other two groups (0.098 ± 0.038 vs. 0.044 ± 0.012, p = .058; 0.044 ± 0.012 vs. 0.007 ± 0.001, p = .057). CONCLUSION: HR-MRI is an accurate direct imaging method and has a high value for the etiological diagnosis of central nervous system vasculitis. DCE-MRI could be an effective way to evaluate and monitor blood-brain barrier to prevent clinical ischemic stroke.


Asunto(s)
Medios de Contraste , Arteria Cerebral Media , Barrera Hematoencefálica , Constricción Patológica/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Arteria Cerebral Media/diagnóstico por imagen
17.
Sensors (Basel) ; 19(10)2019 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-31137853

RESUMEN

Cast fixation is a general clinical skill used for the treatment of fractures. However, it may cause many complications due to careless treatment procedures. Currently, swathing a cast for a patient can only be determined by a doctors' experience; however, this cannot be determined by the value of pressure, temperature, or humidity with objective and reliable equipment. When swathing a cast for a patient, the end result is often too tight or too loose. Hence, in this paper we developed a sensor for detecting pressure, temperature, and humidity, respectively. This could provide reliable reference cast data to help physicians to understand the tightness of cast swathing and to adjust the tightness of cast swathing instantly to alleviate a patient's complications caused by excessive pressure or overheating. In this paper, six pressure sensors and one temperature-humidity sensor are used to detect the pressure, temperature, and humidity in an arm swathed with a cast to confirm whether the tightness of the cast is fixing the fracture efficiently, while avoiding causing any damage by using excessive pressure. Currently, the variation in temperature and humidity can be detected by the inflammation of the wound, displaying secretions, and fever in the cast. Based on the experiments, the voltage and power conversion coefficients of the developed sensors could be compensated for by the nonlinear error of the sensor. The experimental results could be instantly displayed on a human interface, such as a smart mobile device. The average skin pressure in a swathed cast was 12.14 g and ranged from 5.0 g to 17.5 g. A few casts exceeded 37.50 g. The abnormal pressure of wrinkles produced during swathing a cast often ranged from 22.50 g to 38.75 g. This shows that cast wrinkles cause pressure on the skin. The pressure caused by cast wrinkles on bone protrusions ranged from 56.5 g to 84.4 g. Compared to other parts that lacked soft skin cushioning, the pressure of cast wrinkles that occurred in the ulna near the protrusion of the wrist bone increased averagely. The pressure error value was less than 2%, the temperature error was less than 1%, and the humidity error was less than 5%. Therefore, they were all in line with the specifications of commercially available products. The six pressure detection points and one temperature and humidity detection point in our newly designed system can accurately measure the pressure, temperature, and humidity inside the cast, and instantly display the corresponding information by mobile APP. Doctors receive reliable reference data and are instantly able to understand the tightness of the swathed cast and adjust it at any time to avoid complications caused by pressure or overheating due to excessive pressure.


Asunto(s)
Técnicas Biosensibles , Humedad , Piel/fisiopatología , Temperatura , Humanos , Presión , Piel/lesiones , Teléfono Inteligente
18.
Brain Circ ; 4(1): 24-32, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30276333

RESUMEN

BACKGROUND: Tenuigenin (TEN), a major active component of the Chinese herb Polygala tenuifolia root, has been used to improve memory and cognitive function in Traditional Chinese Medicine for centuries. PURPOSE: The present study was designed to explore the possible neuroprotective effect of TEN on the streptozotocin (STZ)-induced rat model of sporadic Alzheimer's disease (sAD). METHODS: STZ was injected twice intracerebroventrically (3 mg/kg, ICV) on alternate days (day 1 and day 3) in Rats. Daily treatment with TEN (2, 4, and 8 mg/kg) starting from the first dose of STZ for 28 days. Memory-related behaviors were evaluated using the Morris water maze test. Hyperphosphorylation of tau proteins in hippocampus were measured by western blot assay. Superoxide dismutase activities, malondialdehyde, glutathione peroxidase and 4-hydroxy-2-nonenal adducts contents were also measured in the hippocampus. RESULTS: Treatment with TEN significantly improved STZ-induced cognitive damage, markedly reduced changes in malondialdehyde and 4-hydroxy-2-nonenal adducts, and significantly inhibited STZ-induced reduction in superoxide dismutase and glutathione peroxidase activities in the hippocampus. In addition, TEN decreased hyperphosphorylation of tau resulting from intracerebroventricular STZ (ICV-STZ) injection, and Nissl staining results showed that TEN has protective effects on hippocampal neurons. CONCLUSION: These results provide experimental evidence demonstrating preventive effect of TEN on cognitive dysfunction, oxidative stress, and hyperphosphorylation of tau in ICV-STZ rats. This study indicates that TEN may have beneficial effects in the treatment of neurodegenerative disorders such as AD.

19.
PLoS One ; 11(9): e0163123, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27690232

RESUMEN

PURPOSE: To investigate the different impacts on patient-reported vision-related quality of life (pVRQOL) outcomes in patients with primary angle-closure glaucoma(PACG) and primary open-angle glaucoma(POAG). METHODS: Prospective cross-sectional study. PACG and POAG patients who had a best-corrected visual acuity(BCVA) in the better eye equal to or better than 20/60, intraocular pressure controlled at or below 25 mmHg and reliable visual field test were invited to participate. The control group included patients with BCVA in the better eye equal to or better than 20/60 and who did not have major eye disease. A validated Taiwanese version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25(T)) was performed to assess pVRQOL. The association between each domain of NEI VFQ-25(T) among 3 groups was determined using multivariable linear regression analysis. RESULTS: A total of 106 PACG, 186 POAG, and 95 controls were enrolled. In multivariable regression analysis of all three groups(PACG/POAG/controls), compared to POAG, PACG showed a weakly positive association with social functioning (R2 = 0.13, ß = 0.22, P = 0.04). PACG showed no significantly negative impact on pVRQOL compared to controls. Taking only glaucoma patients into consideration, PACG patients had a higher score on social functioning compared to POAG (R2 = 0.16, ß = 0.27, P = 0.01). The results of other domains of NEI VFQ-25(T) between the two groups did not differ significantly(p>0.05). CONCLUSIONS: In patients with controlled disease, the impact of PACG and POAG on most domains of NEI VFQ-25(T) were similar, except for better social functioning in PACG compared to POAG.

20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(9): 2540-3, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26669163

RESUMEN

Water vapor in the beam of a Fourier transform infrared (FTIR) spectrometer or/and in a gas cell is a major source of interference in the infrared measurement of a gas sample. In general, in order to eliminate the effect of water vapor, we have to completely remove these molecules before the measurement of any spectrum. Herein, we provide an approach to collect an IR spectrum of a gas (wet acetone) sample free from water vapor interference without any drying pretreatment. After dozens of scans, the air atmosphere in the sample compartment of the FTIR spectrometer will be slightly adjusted by small amounts of dry air or wet air (room air) depending on the property of water vapor lines (absorbance >0 or absorbance <0). Water vapor lines will then gradually disappear when the ensuing collection process is continued. The experiment results demonstrated that this method is a facile and very effective way to remove water vapor interference. Moreover, this method works still well for the measurement at 0.5 cm(-1) resolution, typically used in the gas infrared measurement.

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