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BACKGROUND: Polygonatum kingianum holds significant importance in Traditional Chinese Medicine due to its medicinal properties, characterized by its diverse chemical constituents including polysaccharides, terpenoids, flavonoids, phenols, and phenylpropanoids. The Auxin Response Factor (ARF) is a pivotal transcription factor known for its regulatory role in both primary and secondary metabolite synthesis. However, our understanding of the ARF gene family in P. kingianum remains limited. METHODS AND RESULTS: We employed RNA-Seq to sequence three distinct tissues (leaf, root, and stem) of P. kingianum. The analysis revealed a total of 31,558 differentially expressed genes (DEGs), with 43 species of transcription factors annotated among them. Analyses via gene ontology and the Kyoto Encyclopedia of Genes and Genomes demonstrated that these DEGs were predominantly enriched in metabolic pathways and secondary metabolite biosynthesis. The proposed temporal expression analysis categorized the DEGs into nine clusters, suggesting the same expression trends that may be coordinated in multiple biological processes across the three tissues. Additionally, we conducted screening and expression pattern analysis of the ARF gene family, identifying 12 significantly expressed PkARF genes in P. kingianum roots. This discovery lays the groundwork for investigations into the role of PkARF genes in root growth, development, and secondary metabolism regulation. CONCLUSION: The obtained data and insights serve as a focal point for further research studies, centred on genetic manipulation of growth and secondary metabolism in P. kingianum. Furthermore, these findings contribute to the understanding of functional genomics in P. kingianum, offering valuable genetic resources.
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Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Proteínas de Plantas , Plantas Medicinales , Polygonatum , Transcriptoma , Plantas Medicinales/genética , Plantas Medicinales/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Polygonatum/genética , Polygonatum/metabolismo , Transcriptoma/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilación de la Expresión Génica/métodos , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ontología de Genes , Hojas de la Planta/genética , Hojas de la Planta/metabolismoRESUMEN
Four undescribed compounds including three harzianic acids (1, 3 and 4) and one oxazolidinone (2), along with three known ones (5-7) were isolated from the solid fermented product of endophytic fungus Ilyonectria sp., their structures were elucidated as 1-amino-harzianic acid (1), ilyonectria-oxazolidinone (2),10'-nor- isoharzianic acid (3), isohomoharzianic acid (4), harzianic acid (5), isoharzianic acid (6), homoharzianic acid (7) by means of detailed chemical evidences and spectroscopic data analysis. All the compounds were evaluated for cytotoxicity against SMMC-7721 human cancer cell lines by MTS assay. Among the seven tested compounds, 1-amino-harzianic acid (1) demonstrated well cytotoxic activity against SMMC-7721 with IC50 value of 26.84 µM. The results of molecular docking indicated that compound exhibited moderate anti-tumor activity may through binding to apoptosis related proteins.
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Antineoplásicos , Simulación del Acoplamiento Molecular , Oxazolidinonas , Humanos , Línea Celular Tumoral , Estructura Molecular , Antineoplásicos/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/química , Oxazolidinonas/farmacología , Oxazolidinonas/aislamiento & purificación , Endófitos/química , China , Hypocreales/químicaRESUMEN
BACKGROUND: Pulmonary mucoepidermoid carcinoma (PMEC) is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree. The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges, primarily attributable to its morphological similarity to other tumors containing clear cells. CASE SUMMARY: A 22-year-old male, formerly in good health, came in with a two-month duration of persistent cough and production of sputum. Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus, which resulted in complete atelectasis of the left lung. Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor, characterized by clear cell morphology in most of the tumor cells. The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection. Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion, leading to a definitive pathological diagnosis of the clear cell variant of PMEC, staged as T2N0M0. After surgery, the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period. CONCLUSION: This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male. The patient underwent successful left lower lobe sleeve resection. This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy, underscoring the importance of precise diagnosis and personalized treatment strategies.
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The objective of this study is to investigate the expression of protein tyrosine phosphatase type I (PTP4A1) in circulating tumor cells (CTCs) in patients with early- and intermediate-stage esophageal cancer and its clinical value in evaluating patient prognosis. Tissue and peripheral blood samples were collected from patients with esophageal cancer, as well as their clinical data. Follow-up was performed on all patients. PTP4A1 expression in the CTCs of patients were analyzed by regression analysis, and its correlation with the clinical characteristics of esophageal cancer was discussed. The numbers of mixed tumor cells and T-CTCs were significantly correlated with lymph node metastasis. Advanced tumor-node metastasis (TNM) stage (odds ratioâ =â 12.063) and lymph node metastasis (odds ratioâ =â 13.541) were influencing factors of PTP4A1+MCTC expression disorders in patients with esophageal cancer. The receiver operating characteristic curve showed that TNM stage and lymph node metastasis had a high predictive efficiency for PTP4A1+MCTCs, with an area under the ROC curve of 0.725. PTP4A1+mixed tumor cells had strong predictive value for the efficacy of neoadjuvant therapy, with a sensitivity of 94.7% and a specificity of 63.6%. Advanced TNM stage and lymph node metastasis are influencing factors for increased CTCs and poor expression of PTP4A1 in patients with esophageal cancer.
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Neoplasias Esofágicas , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patología , Metástasis Linfática , Pronóstico , Neoplasias Esofágicas/patología , Proteínas Tirosina Fosfatasas , Proteínas de la Membrana , Proteínas de Ciclo CelularRESUMEN
BACKGROUND: Pulmonary mucormycosis is a rare but life-threatening invasive fungal infection that mostly affects immunocompromised patients. This disease usually develops acutely and progresses rapidly, often leading to a poor clinical prognosis. Chronic pulmonary mucormycosis is highly unusual in immunocompetent patients. CASE SUMMARY: A 43-year-old man, who was a house improvement worker with a long history of occupational dust exposure, presented with an irritating cough that had lasted for two months. The patient was previously in good health, without dysglycemia or any known immunodeficiencies. Chest computed tomography revealed a mass in the left lower lobe, measuring approximately 6 cm in diameter, which was suspected to be primary lung carcinoma complicated with obstructive pneumonia. Thoracoscopic-assisted left lower lobectomy was performed, and metagenomic next-generation sequencing detection, along with special pathological staining of surgical specimens, suggested Rhizopus microsporus infection. Postoperatively, the patient's respiratory symptoms were relieved, and no signs of recurrence were found during the six-month follow-up. CONCLUSION: This article reports a rare case of chronic pulmonary mucormycosis caused by Rhizopus microsporus in a middle-aged male without dysglycemia or immunodeficiency. The patient's surgical outcome was excellent, reaffirming that surgery remains the cornerstone of pulmonary mucormycosis treatment.
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BACKGROUND: Birth asphyxia causes hypoxia or inadequate perfusion to the organs of newborns, leading to metabolism dysfunctions including blood glucose disorders. METHODS: Neonates with and without birth asphyxia were retrospectively recruited from 53 hospitals in Hubei Province from January 1 to December 31, 2018. In summary, 875, 1139, and 180 cases in the control group, the mild asphyxia group, and the severe asphyxia group were recruited, respectively. Neonatal blood glucose values at postnatal 1, 2, 6, and 12 h (time error within 0.5 h was allowed) were gathered from the medical records. RESULTS: The incidence rates of hyperglycemia in the control group, the mild asphyxia group and the severe asphyxia group were 2.97%, 7.90%, and 23.33%, respectively (p < 0.001). Additionally, the incidence rates of hypoglycemia in the three groups above were 3.66%, 4.13%, and 7.78%, respectively (p = 0.042). The blood glucose values of neonates with hypoglycemia in the asphyxia group were lower than in the control group (p = 0.003). Furthermore, the blood glucose values of neonates with hyperglycemia were highest in the severe asphyxia group (p < 0.001). There were 778 and 117 cases with blood glucose records at four predefined time points in the mild and severe asphyxia group, respectively. The incidence of blood glucose disorders in the mild asphyxia group significantly decreased from postnatal 6 h (pï¼0.05). However, we found no obvious changes of the incidence of glucose disorders within postnatal 12 h in the severe asphyxia group (p = 0.589). CONCLUSION: Birth asphyxia is likely to cause neonatal blood glucose disorders, both hypoglycemia and hyperglycemia, during the early postnatal life. The neonates with severe asphyxia have higher incidence, worse severity and longer duration of blood glucose disorders than neonates with mild asphyxia.
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Asfixia Neonatal , Hiperglucemia , Hipoglucemia , Enfermedades del Recién Nacido , Humanos , Recién Nacido , Glucemia , Asfixia , Estudios Retrospectivos , Asfixia Neonatal/epidemiología , Enfermedades del Recién Nacido/epidemiología , Hipoglucemia/epidemiología , Hipoglucemia/etiología , Hiperglucemia/epidemiología , China/epidemiologíaRESUMEN
BACKGROUND: Thymolipoma is a rare benign tumor arising from the anterior mediastinal thymus and is composed of mature fatty tissue and interspersed nonneoplastic thymic tissue. This tumor accounts for only a small percentage of mediastinal masses, and the majority of them are asymptomatic and found incidentally. To date, fewer than 200 cases have been published in the world literature, of which most excised tumors weighed less than 0.5 kg and the largest weighed 6 kg. CASE SUMMARY: A 23-year-old man presented with a complaint of progressive breathlessness for 6 mo. His forced vital capacity was only 23.6% of the predicted capacity, and his arterial partial pressure of oxygen and carbon dioxide were 51 and 60 mmHg, respectively, without oxygen inhalation. Chest computed tomography revealed a large fat-containing mass in the anterior mediastinum that measured 26 cm × 20 cm × 30 cm in size and occupied most of the thoracic cavity. Percutaneous mass biopsy revealed only thymic tissue without signs of malignancy. A right posterolateral thoracotomy was successfully performed to remove the tumor along with the capsule, and the excised tumor weighed 7.5 kg, which to our knowledge, was the largest surgically removed tumor of thymic origin. Postoperatively, the patient's shortness of breath was resolved, and the histopathological diagnosis was thymolipoma. No signs of recurrence were observed at the 6-mo follow-up. CONCLUSION: Giant thymolipoma causing respiratory failure is rare and dangerous. Despite the high risks, surgical resection is feasible and effective.
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Phytochemical analyses of Swertia davidii Franch. extracts using column chromatography and semi-preparative HPLC were performed. Two novel phenolic glycosides named swertiosides A and B (compounds 1 and 2, respectively) were isolated and characterized. Four known phenolic glycosides were also extracted (compounds 3-6). The structural characteristics of these novel compounds were analyzed using 1D, 2D NMR, and HRMS. All six compounds have never been isolated from this particular plant species before this study. Subsequent assessment of bioactive properties suggested that compounds 1 and 2 exhibited moderate levels of cytotoxicity.
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Lignanos , Swertia , Lignanos/farmacología , Swertia/química , Glicósidos/farmacología , Glicósidos/química , Extractos Vegetales/química , Espectroscopía de Resonancia Magnética , Fenoles/farmacología , Fenoles/químicaRESUMEN
Objectives: Spinal fusion is a widely employed treatment of patients with degenerative disc disease, in which a cage is used to replace the disc for spinal fusion. But it often fails for insufficient mechanical strength and poor osseointegration. Here, we designed a polyether-ether-ketone (PEEK)/tantalum (Ta) composite cage with a biomimetic gradient porous micro-structure, simultaneously enhancing mechanical properties and accelerating osseointegration in spinal fusion. Materials and methods: In the study, based on the mechanical performances of PEEK and osteogenic potential of Ta, and the three-dimensional (3D) structures of cuttlebone and vertebra, the cages were respectively 3D printed by pure PEEK, PEEK with 5 wt% Ta (PEEK/Ta-5), PEEK with 10 wt% Ta (PEEK/Ta-10) and PEEK with 15 wt% Ta (PEEK/Ta-15), then verified in vitro and in sheep cervical fusion model systematically. Results: Vertebral Gyroid structure PEEK/Ta-15 cage exhibited superior mechanical properties than Cuttlebone-like structure PEEK/Ta-15 cage, closer to the cervical vertebra. Furthermore, PEEK/Ta-15 cage with higher Ta microparticles in PEEK provided a biomimetic gradient porous micro-structure with higher surface energy, guiding cell biological behavior, promoting new bone penetration, and accelerating osseointegration in vivo. Conclusion: In conclusion, the study designed a biomimetic gradient porous cage with a micro-structure for enhancing mechanical properties, accelerating osseointegration and forming an anatomical lock in the fusion segment through composites, mechanical efficiency, surface extension, and pores.
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The lateral hypothalamus (LH) is an important brain region mediating sleep-wake behavior. Recent evidence has shown that astrocytes in central nervous system modulate the activity of adjacent neurons and participate in several physiological functions. However, the role of LH astrocytes in sleep-wake regulation remains unclear. Here, using synchronous recording of electroencephalogram/electromyogram in mice and calcium signals in LH astrocytes, we show that the activity of LH astrocytes is significantly increased during non-rapid eye movement (NREM) sleep-to-wake transitions and decreased during Wake-to-NREM sleep transitions. Chemogenetic activation of LH astrocytes potently promotes wakefulness and maintains long-term arousal, while chemogenetic inhibition of LH astrocytes decreases the total amount of wakefulness in mice. Moreover, by combining chemogenetics with fiber photometry, we show that activation of LH astrocytes significantly increases the calcium signals of adjacent neurons, especially among GABAergic neurons. Taken together, our results clearly illustrate that LH astrocytes are a key neural substrate regulating wakefulness and encode this behavior through surrounding GABAergic neurons. Our findings raise the possibility that overactivity of LH astrocytes may be an underlying mechanism of clinical sleep disorders.
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Área Hipotalámica Lateral , Vigilia , Animales , Ratones , Vigilia/fisiología , Área Hipotalámica Lateral/fisiología , Astrocitos , Calcio , Sueño/fisiología , Neuronas GABAérgicas/fisiología , HipotálamoRESUMEN
The dorsal raphe nucleus (DRN) has previously been proved to be involved in the regulation of the sleep-wake behavior. DRN contains several neuron types, such as 5-HTergic and GABAergic neurons. GABAergic neurons, which are the second largest cell subtype in the DRN, participate in a variety of neurophysiological functions. However, their role in sleep-wake regulation and the underlying neural circuitry remains unclear. Herein, we used fiber photometry and synchronous electroencephalogram (EEG)/electromyography (EMG) recording to demonstrate that DRN GABAergic neurons exhibit high activities during wakefulness and low activities during NREM sleep. Short-term optogenetic activation of DRN GABAergic neurons reduced the latency of NREM-to-wake transition and increased the probability of wakefulness, while long-term optogenetic activation of these neurons significantly increased the amount of wakefulness. Chemogenetic activation of DRN GABAergic neurons increased wakefulness for almost 2 h and maintained long-lasting arousal. In addition, inhibition of DRN GABAergic neurons with chemogenetics caused a reduction in the amount of wakefulness. Finally, similar to the effects of activating the soma of DRN GABAergic neurons, optogenetic stimulation of their terminals in the ventral tegmental area (VTA) induced instant arousal and promoted wakefulness. Taken together, our results illustrated that DRN GABAergic neurons are vital to the induction and maintenance of wakefulness, which promote wakefulness through the GABAergic DRN-VTA pathway.
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Núcleo Dorsal del Rafe , Área Tegmental Ventral , Área Tegmental Ventral/metabolismo , Vigilia/fisiología , Sueño/fisiología , Neuronas GABAérgicas/fisiologíaRESUMEN
This study was performed to uncover the effects of dexmedetomidine on oxidative stress injury induced by mitochondrial localization of telomerase reverse transcriptase (TERT) in enteric glial cells (EGCs) following intestinal ischaemia-reperfusion injury (IRI) in rat models. Following establishment of intestinal IRI models by superior mesenteric artery occlusion in Wistar rats, the expression and distribution patterns of TERT were detected. The IRI rats were subsequently treated with low or high doses of dexmedetomidine, followed by detection of ROS, MDA and GSH levels. Calcein cobalt and rhodamine 123 staining were also carried out to detect mitochondrial permeability transition pore (MPTP) and the mitochondrial membrane potential (MMP), respectively. Moreover, oxidative injury of mtDNA was determined, in addition to analyses of EGC viability and apoptosis. Intestinal tissues and mitochondria of EGCs were badly damaged in the intestinal IRI group. In addition, there was a reduction in mitochondrial localization of TERT, oxidative stress, whilst apoptosis of EGCs was increased and proliferation was decreased. On the other hand, administration of dexmedetomidine was associated with promotion of mitochondrial localization of TERT, whilst oxidative stress, MPTP and mtDNA in EGCs, and EGC apoptosis were all inhibited, and the MMP and EGC viability were both increased. A positive correlation was observed between different doses of dexmedetomidine and protective effects. Collectively, our findings highlighted the antioxidative effects of dexmedetomidine on EGCs following intestinal IRI, as dexmedetomidine alleviated mitochondrial damage by enhancing the mitochondrial localization of TERT.
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Dexmedetomidina , Daño por Reperfusión , Telomerasa , Animales , Ratas , Dexmedetomidina/farmacología , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial , Neuroglía/metabolismo , Ratas Wistar , Daño por Reperfusión/complicaciones , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Telomerasa/metabolismoRESUMEN
Because of their strong anti-cancer efficacy with fewer side effects, traditional Chinese medicines (TCM) have attracted considerable attention for their potential application in treating breast cancer (BC). However, knowledge about the underlying systematic mechanisms is scarce. Gynostemma pentaphyllum (Thunb.) Makino (GP), a creeping herb, has been regularly used as a TCM to prevent and treat tumors including BC. Again, mechanisms underlying its anti-BC properties have remained elusive. We used network pharmacology and molecular docking to explore the mechanistic details of GP against BC. The TCM systems pharmacology database and analysis platform and PharmMapper Server database were used to retrieve the chemical constituents and potential targets in GP. In addition, targets related to BC were identified using DrugBank and Therapeutic Target Database. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of crucial targets were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and database for annotation, visualization, and integrated discovery databases, whereas the network visualization analysis was performed using Cytoscape 3.8.2. In addition, the molecular docking technique was used to validate network pharmacology-based predictions. A comparison of the predicted targets of GP with those of BC-related drugs revealed 26 potential key targets related to the treatment of BC, among which ALB, EGFR, ESR1, AR, PGR, and HSP90AA1 were considered the major potential targets. Finally, network pharmacology-based prediction results were preliminarily verified by molecular docking experiments. In addition, chemical constituents and potential target proteins were scored, followed by a comparison with the ligands of the protein. We provide a network of pharmacology-based molecular mechanistic insights on the therapeutic action of GP against BC. We believe that our data will serve as a basis to conduct future studies and promote the clinical applications of GP.
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Neoplasias de la Mama , Medicamentos Herbarios Chinos , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Gynostemma , Farmacología en Red , Mapas de Interacción de Proteínas , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Objective: Codonopsis Radix and Polygonati Rhizoma (CRPR) has a good hypoglycemic effect. The aims of the present study were to investigate the effect of CRPR on high-fat/high-sugar diet (HFHSD)- and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) mice as well as to investigate the involved mechanism. Methods: A T2DM mouse model was generated by combining HFHSD and STZ. After the model was established, normal and model groups received the same volume of normal saline intragastrically, and the negative control group was treated with metformin (200 mg/kg·BW). The low, medium, and high CRPR groups received four consecutive weeks of oral gavage with CRPR doses of 2.5, 5, and 10 g/kg·BW, respectively, during the course of the study. Body weight and fasting blood glucose (FBG) were measured on a weekly basis. Enzyme-linked immunosorbent assay (ELISAs) were used to evaluate the serum and liver samples. Hematoxylin and eosin (H&E) staining was utilized to observe the pathological status of the liver and pancreas. Western blot (WB) analysis was performed to evaluate the protein expression levels of PI3K, p-PI3K, AKT, and p-AKT. Results: Compared to model mice, each treatment group had significantly elevated levels of FBG, total cholesterol (TC), and triacylglycerol (TG) (P<0.01 and P<0.05, respectively). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly reduced in the treatment groups compared to the model group (P<0.01). Compared to the model group, fasting insulin (FINS) levels were elevated in all groups of CRPR (P<0.05), and there were significantly higher levels of high-density lipoprotein cholesterol (HDL-C) in both the low-dose and high-dose CRPR groups (P<0.05). H&E staining indicated that CRPR treatment reduced organ enlargement, improved liver lipid accumulation, and repaired islet injury in T2DM mice. Moreover, WB analysis demonstrated that all CRPR groups significantly upregulated the protein expression of IRS1, p-GSK3ß, PI3K, p-Akt and p-FOXO1(P<0.05) as well as significantly downregulated p-IRS1 and FOXO1 protein expression (P<0.05). Conclusion: The present study demonstrated that CRPR effectively improves the metabolic disturbance of lipids, repairs damaged liver tissues, repairs damaged pancreatic tissues, and reduces insulin resistance (IR) in T2DM mice. The mechanism of action may be associated with upregulation of the IRS1/PI3K/AKT signaling pathway and inhibition of IRS1 phosphorylation.
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Codonopsis , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Codonopsis/metabolismo , Glucemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Transducción de Señal , Colesterol/efectos adversosRESUMEN
Chlorogenic acid (CGA) is a potential inhibitor of Coronavirus Disease 2019 (COVID-19). ACE2 and its co-expressed proteins are SARS-CoV-2 receptors, which have been linked to SARS-CoV-2 infection and considered as the key target of SARS-CoV-2 in entering target cells. Here, network pharmacology was used to investigate the mechanism by which CGA affected COVID-19. A total of 70 potential targets related to the treatment of COVID-19 were obtained, among which NFE2L2, PPARG, ESR1, ACE, IL6, and HMOX1 might be the main potential targets. Finally, CGA and potential target proteins were scored by molecular docking, and the prediction results of network pharmacology were preliminarily verified. Moreover, CGA had potential anti-SARS-CoV-2 activity via integrating three common receptors in clinical practice compared with clinical trial drugs registered for the treatment of COVID-19, as shown by molecular docking. The mechanism of CGA against COVID-19 was initially investigated using network pharmacology, followed by molecular docking.
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Productos Biológicos , Tratamiento Farmacológico de COVID-19 , Medicamentos Herbarios Chinos , Ácido Clorogénico/farmacología , Medicamentos Herbarios Chinos/farmacología , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , SARS-CoV-2RESUMEN
OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, P<0.05) or with severe asphyxia (19.8% vs 8.1%, P<0.05) or hypothermia therapy (4.8% vs 1.5%, P<0.05), as well as a significantly higher incidence rate of disorder of glucose metabolism (18.8% vs 12.5%, P<0.05). Compared with the good prognosis group, the poor prognosis group had a significantly higher incidence rate of disorder of glucose metabolism at 1, 2, and 6 hours after birth (P<0.05). The multivariate logistic regression analysis showed that recurrent hyperglycemia (adjusted odds ratio=2.380, 95% confidence interval: 1.275-4.442, P<0.05) was an independent risk factor for poor prognosis in neonates with asphyxia. CONCLUSIONS: Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.
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Asfixia Neonatal , Hiperglucemia , Asfixia , Asfixia Neonatal/complicaciones , Asfixia Neonatal/epidemiología , Humanos , Recién Nacido , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury commonly occurs during perioperative periods, resulting in high morbidity and mortality on a global scale. Dexmedetomidine (Dex) is a selective α2-agonist that is frequently applied during perioperative periods for its analgesia effect; however, its ability to provide protection against intestinal I/R injury and underlying molecular mechanisms remain unclear. METHODS: To fill this gap, the protection of Dex against I/R injury was examined in a rat model of intestinal I/R injury and in an inflammation cell model, which was induced by tumor necrosis factor-alpha (TNF-α) plus interferon-gamma (IFN-γ) stimulation. RESULTS: Our data demonstrated that Dex had protective effects against intestinal I/R injury in rats. Dex was also found to promote mitophagy and inhibit apoptosis of enteric glial cells (EGCs) in the inflammation cell model. PINK1 downregulated p53 expression by promoting the phosphorylation of HDAC3. Further studies revealed that Dex provided protection against experimentally induced intestinal I/R injury in rats, while enhancing mitophagy, and suppressing apoptosis of EGCs through SIRT3-mediated PINK1/HDAC3/p53 pathway in the inflammation cell model. CONCLUSION: Hence, these findings provide evidence supporting the protective effect of Dex against intestinal I/R injury and its underlying mechanism involving the SIRT3/PINK1/HDAC3/p53 axis.
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Dexmedetomidina , Daño por Reperfusión , Sirtuina 3 , Animales , Apoptosis , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Isquemia , Mitocondrias , Neuroglía , Proteínas Quinasas , Ratas , Daño por Reperfusión/tratamiento farmacológico , Proteína p53 Supresora de TumorRESUMEN
Synchronous double primary lung squamous carcinoma (sDPLSCC) is rare and difficult to distinguish from metastatic disease, histopathologically. Owing to the heterogeneity of cancer, it is also difficult to select the optimal therapeutic strategy for patients with multiple primary lung cancer (MPLC). The present study reports a rare case of a 61-year-old male patient with sDPLSCC diagnosed using histology and genetic profiling. LSCC-related driver mutations were detected in this patient, and we reported the TP53 c.475G>C mutation, which has been detected in both breast cancer and hepatocellular carcinoma, but not previously in lung squamous carcinoma. Our findings provide further evidence supporting the necessity of genetic testing for primary tumor diagnosis.