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BACKGROUND: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. METHODS: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. RESULTS: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. CONCLUSIONS: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC.
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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.
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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.
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Lesões das Artérias Carótidas , Artéria Carótida Interna , Neoplasias Hipofisárias , Stents , Humanos , Feminino , Lesões das Artérias Carótidas/etiologia , Lesões das Artérias Carótidas/cirurgia , Lesões das Artérias Carótidas/terapia , Neoplasias Hipofisárias/cirurgia , Idoso , Artéria Carótida Interna/cirurgia , Adenoma/cirurgia , Endoscopia/métodos , Falso Aneurisma/etiologia , Falso Aneurisma/cirurgia , Falso Aneurisma/terapia , Falso Aneurisma/diagnóstico por imagem , Angiografia Cerebral , Recidiva , Complicações Intraoperatórias/etiologiaRESUMO
This study took Chinese patent medicine for children included in Chinese Pharmacopoeia(2020 edition and the first supplement), Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance(2022 edition), and National Essential Medicines List(2018 edition) as the research objects, so as to sort out the distribution situation, characteristics, and the problems of Chinese patent medicine for children(including child-specific medicines, common medicines for children and adults, and discretionary medicines for children). According to statistics and summary, Chinese patent medicine for children is mainly administered orally, and the dosage forms are mostly traditional dosage forms, such as tablets, granules, capsules, and oral liquids, with mostly bitter or sweet taste. Diseases are mainly classified into pulmonary diseases and spleen and stomach diseases, and varieties of medication without Children's medication safety information or "still unclear" account for a relatively large proportion of the medicines. There are relatively few varieties of Chinese patent medicines for children, poor compliance of child-specific medication, lack of refinement of Chinese patent medicines for children dosage, and lack of information about safe use of medication. It is recommended to update and improve the instruction manuals in a timely manner, develop new varieties of Chinese patent medicine for children, and actively carry out post-marketing evaluation and clinical comprehensive evaluation of Chinese patent medicine for children, so as to provide a reference for the supplement and improvement of the instructions, the comprehensive improvement, the formulation of the catalogue, and the research and development of new Chinese patent medicine for children and ensure the use of medicines for children.
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Medicamentos de Ervas Chinesas , Humanos , Criança , China , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos sem Prescrição , Medicina Tradicional Chinesa , Pré-Escolar , Lactente , AdolescenteRESUMO
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.
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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.
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Parafusos Ósseos , Fraturas do Quadril , Humanos , Estudos Retrospectivos , Radiografia , Cuidados Pós-Operatórios , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgiaRESUMO
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.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células A549 , Animais , Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Proteínas de Ligação a RNA/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de SinaisRESUMO
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.
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Técnicas Biossensoriais , Umidade , Pele/fisiopatologia , Temperatura , Humanos , Pressão , Pele/lesões , SmartphoneRESUMO
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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Infrared spectral studies of aqueous solution have been severely limited by the strong water absorption. Usually, it is very difficult to experimentally achieve perfect compensation between the amount of water that contributes to the sample and background spectra. In the present paper, we introduced a new method to make the infrared bands of water disappear during the measurement of an infrared spectrum for aqueous solution. Both background spectrum of the empty ATR cell and that of the water on ATR cell are used in sequence. Qualified infrared spectra of 10% K2CO3 and 10% BSA aqueous solutions were successfully obtained by ATR accessory (single-reflection) without water interference. The experimental results demonstrated that the new method is fast, effective and powerful. The limitation of the new method is also discussed.
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One of the greatest challenges in genetic studies is the determination of gene-environment interactions due to underlying complications and inadequate statistical power. With the increased sample size gained by using case-parent trios and unrelated cases and controls, the performance may be much improved. Focusing on a dichotomous trait, a two-stage approach was previously proposed to deal with gene-environment interaction when utilizing mixed study samples. Theoretically, the two-stage association analysis uses likelihood functions such that the computational algorithms may not converge in the maximum likelihood estimation with small study samples. In an effort to avoid such convergence issues, we propose a logistic regression framework model, based on the combined haplotype relative risk (CHRR) method, which intuitively pools the case-parent trios and unrelated subjects in a two by two table. A positive feature of the logistic regression model is the effortless adjustment for either discrete or continuous covariates. According to computer simulations, under the circumstances in which the two-stage test converges in larger sample sizes, we discovered that the performances of the two tests were quite similar; the two-stage test is more powerful under the dominant and additive disease models, but the extended CHRR is more powerful under the recessive disease model.
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Interação Gene-Ambiente , Modelos Logísticos , Algoritmos , Alelos , Estudos de Casos e Controles , Simulação por Computador , Frequência do Gene , Humanos , Modelos Genéticos , Modelos EstatísticosRESUMO
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.
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Células Endoteliais , Monocrotalina , Poliaminas , Hipertensão Arterial Pulmonar , Artéria Pulmonar , Purinas , Ratos Sprague-Dawley , Espermidina , Remodelação Vascular , Animais , Espermidina/farmacologia , Espermidina/uso terapêutico , Purinas/farmacologia , Poliaminas/metabolismo , Masculino , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Remodelação Vascular/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Ratos , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/induzido quimicamente , Hipertensão Arterial Pulmonar/metabolismo , Células Cultivadas , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Purina-Núcleosídeo Fosforilase/metabolismo , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/metabolismo , Adenosilmetionina Descarboxilase/metabolismo , Modelos Animais de Doenças , HumanosRESUMO
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.
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Chalcona , Chalcona/análogos & derivados , Medicamentos de Ervas Chinesas , Hipertensão Arterial Pulmonar , Quinonas , Humanos , Animais , Ratos , Hipertensão Arterial Pulmonar/induzido quimicamente , Hipertensão Arterial Pulmonar/tratamento farmacológico , Remodelação Vascular , Simulação de Acoplamento Molecular , Chalcona/farmacologiaRESUMO
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.
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Hipertensão Pulmonar , MicroRNAs , Hipertensão Arterial Pulmonar , Humanos , Ratos , Animais , Hipertrofia Ventricular Direita , Hipertensão Arterial Pulmonar/complicações , Ácido Butírico/farmacologia , Ácido Butírico/uso terapêutico , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar Primária Familiar , MicroRNAs/genética , MicroRNAs/metabolismo , Fator de Crescimento Insulin-Like IRESUMO
Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+ mice.
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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.
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Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Células-Tronco Neoplásicas , RNA Circular , Fatores de Transcrição SOX9 , Neoplasias Gástricas , Fator de Transcrição 4 , beta Catenina , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Humanos , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição SOX9/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , beta Catenina/metabolismo , beta Catenina/genética , RNA Circular/genética , RNA Circular/metabolismo , Fator de Transcrição 4/genética , Fator de Transcrição 4/metabolismo , Animais , Camundongos , Linhagem Celular Tumoral , Camundongos Nus , Masculino , Feminino , Resistencia a Medicamentos Antineoplásicos/genética , Camundongos Endogâmicos BALB C , Pessoa de Meia-IdadeRESUMO
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.
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Diabetes Gestacional , Eczema , Hipersensibilidade , Gravidez , Feminino , Humanos , Pré-Escolar , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Hipersensibilidade/epidemiologia , GlucoseRESUMO
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.
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Hipertensão Pulmonar , Camundongos , Animais , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Resveratrol/farmacologia , Resveratrol/metabolismo , Vimentina/metabolismo , Células Endoteliais/metabolismo , Remodelação Vascular , Hipóxia/complicações , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Artéria Pulmonar , Miócitos de Músculo Liso , Proliferação de Células , Células CultivadasRESUMO
The ideal 100% line could not be obtained when the content of water vapor in the spectrometer is constant but high during the whole procedure of a far-infrared spectrum collection. This result indicates that anomalous absorption phenomenon takes place in high relative humidity atmosphere. In the present paper, the influences of the relative humidity of ambient air and spectral resolution on anomalous absorption were studied. It was found that both decreasing the water vapor content in the spectrometer and adopting low spectral resolution are effective methods to avoid anomalous absorption. Furthermore, the water vapor bands can be eliminated by "dry air and wet air titration" in the fluctuant humidity. This provides us a quick and economic method to obtain a qualified far infrared spectrum conveniently. It should be noticed that the working condition for "dry air and wet air titration" is low relative humidity to prevent water vapor abnormal absorption.
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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.