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1.
Cell ; 186(4): 748-763.e15, 2023 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-36758548

RESUMEN

Although many prokaryotes have glycolysis alternatives, it's considered as the only energy-generating glucose catabolic pathway in eukaryotes. Here, we managed to create a hybrid-glycolysis yeast. Subsequently, we identified an inositol pyrophosphatase encoded by OCA5 that could regulate glycolysis and respiration by adjusting 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) levels. 5-InsP7 levels could regulate the expression of genes involved in glycolysis and respiration, representing a global mechanism that could sense ATP levels and regulate central carbon metabolism. The hybrid-glycolysis yeast did not produce ethanol during growth under excess glucose and could produce 2.68 g/L free fatty acids, which is the highest reported production in shake flask of Saccharomyces cerevisiae. This study demonstrated the significance of hybrid-glycolysis yeast and determined Oca5 as an inositol pyrophosphatase controlling the balance between glycolysis and respiration, which may shed light on the role of inositol pyrophosphates in regulating eukaryotic metabolism.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Difosfatos/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fosfatos de Inositol/genética , Fosfatos de Inositol/metabolismo , Glucólisis/genética , Respiración , Pirofosfatasas/metabolismo , Glucosa/metabolismo
2.
Development ; 148(12)2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-34013332

RESUMEN

Eukaryotic translation initiation factor 4E (eIF4E) mediates cap-dependent translation. Genetic and inhibitor studies show that eIF4E expression is required for the successful transition from maternal to embryonic control of mouse embryo development. eIF4E was present in the oocyte and in the cytoplasm soon after fertilization and during each stage of early development. Functional knockout (Eif4e-/-) by PiggyBac [Act-RFP] transposition resulted in peri-implantation embryonic lethality because of the failure of normal epiblast formation. Maternal stores of eIF4E supported development up to the two- to four-cell stage, after which new expression occurred from both maternal and paternal inherited alleles. Inhibition of the maternally acquired stores of eIF4E (using the inhibitor 4EGI-1) resulted in a block at the two-cell stage. eIF4E activity was required for new protein synthesis in the two-cell embryo and Eif4e-/- embryos had lower translational activity compared with wild-type embryos. eIF4E-binding protein 1 (4E-BP1) is a hypophosphorylation-dependent negative regulator of eIF4E. mTOR activity was required for 4E-BP1 phosphorylation and inhibiting mTOR retarded embryo development. Thus, this study shows that eIF4E activity is regulated at key embryonic transitions in the mammalian embryo and is essential for the successful transition from maternal to embryonic control of development.


Asunto(s)
Desarrollo Embrionario/genética , Factor 4E Eucariótico de Iniciación/genética , Regulación del Desarrollo de la Expresión Génica , Animales , Elementos Transponibles de ADN , Embrión de Mamíferos , Factor 4E Eucariótico de Iniciación/metabolismo , Técnica del Anticuerpo Fluorescente , Ratones , Ratones Noqueados , Oocitos/metabolismo , Biosíntesis de Proteínas
3.
J Urol ; 211(1): 90-100, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37788015

RESUMEN

PURPOSE: Penile cancer is rare, with significant morbidity and limited literature assessing utility of peripheral and deep en face margin assessment (PDEMA) vs traditional margin assessment (vertical sections) on treatment outcomes. MATERIALS AND METHODS: This was a 32-year retrospective multicenter cohort study at 3 academic tertiary care centers. The cohort consisted of 189 patients with histologic diagnosis of in situ or T1a cutaneous squamous cell carcinoma of the penis at Brigham and Women's, Massachusetts General Hospital (1988-2020), and Memorial Sloan Kettering Cancer Center (1995-2020) treated with PDEMA surgical excision, excision/circumcision, or penectomy/glansectomy. Local recurrence, metastasis, and disease-specific death were assessed via multivariable Cox proportional hazard models. RESULTS: The cohort consisted of 189 patients. Median age at diagnosis was 62 years. Median tumor diameter was 1.3 cm. The following outcomes of interest occurred: 30 local recurrences, 13 metastases, and 5 disease-specific deaths. Primary tumors were excised with PDEMA (N = 30), excision/circumcision (N = 110), or penectomy/glansectomy (N = 49). Of patients treated with traditional margin assessment (non-PDEMA), 12% had narrow or positive margins. Five-year proportions were as follows with respect to local recurrence-free survival, metastasis-free survival, and disease-specific survival/progression-free survival, respectively: 100%, 100%, and 100% following PDEMA; 82%, 96%, and 99% following excision/circumcision; 83%, 91%, and 95% following penectomy/glansectomy. A limitation is that this multi-institutional cohort study was not externally validated. CONCLUSIONS: Initial results are encouraging that PDEMA surgical management effectively controls early-stage penile squamous cell carcinoma.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Pene , Neoplasias Cutáneas , Masculino , Humanos , Femenino , Persona de Mediana Edad , Neoplasias del Pene/patología , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Tratamientos Conservadores del Órgano/métodos , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos
4.
Chemistry ; 30(4): e202303319, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38010959

RESUMEN

With the extensive use of fossil fuels, the ever-increasing greenhouse gas of mainly carbon dioxide emissions will result in global climate change. It is of utmost importance to reduce carbon dioxide emissions and its utilization. Li-CO2 batteries can convert carbon dioxide into electrochemical energy. However, developing efficient catalysts for the decomposition of Li2 CO3 as the discharge product represents a challenge in Li-CO2 batteries. Herein, we demonstrate a carbon foam composite with growing carbon nanotube by using cobalt as the catalyst, showing the ability to enhance the decomposition rate of Li2 CO3 , and thus improve the electrochemical performance of Li-CO2 batteries. Benefiting from its abundant pore structure and catalytic sites, the as-assembled Li-CO2 battery exhibits a desirable overpotential of 1.67 V after 50 cycles. Moreover, the overpotentials are 1.05 and 2.38 V at current densities of 0.02 and 0.20 mA cm-2 , respectively. These results provide a new avenue for the development of efficient catalysts for Li-CO2 batteries.

5.
Pediatr Blood Cancer ; 71(2): e30790, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38053241

RESUMEN

It is unknown how common job lock (i.e., staying at job to maintain health insurance) remains among childhood cancer survivors after Affordable Care Act (ACA) implementation in 2010. We examined prevalence of and factors associated with job lock using a cross-sectional survey from the Childhood Cancer Survivor Study (3503 survivors; 942 siblings). Survivor, spousal, and any survivor/spouse job lock were more frequently reported by survivors than siblings. Survivor job lock/any job lock was associated with older age, low income, severe chronic conditions, and debt/inability to pay debt. Job lock remains more common among survivors than siblings after ACA implementation.


Asunto(s)
Supervivientes de Cáncer , Neoplasias , Estados Unidos/epidemiología , Humanos , Niño , Neoplasias/epidemiología , Patient Protection and Affordable Care Act , Estudios Transversales , Esposos , Sobrevivientes , Hermanos
6.
BMC Neurol ; 24(1): 188, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38840065

RESUMEN

BACKGROUND: Myasthenia gravis (MG) is a long-term autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue as its primary clinical features. Vitamin D is crucial for both the autoimmune response and skeletal muscle function. CASE PRESENTATION: Here, we presented a case report documenting the substantial improvement in symptoms experienced by a patient who underwent subtotal gastrectomy for gastric cancer following high-dose Vitamin D supplementation. The patient developed generalized MG two months after the surgery and did not respond adequately to pyridostigmine therapy, experiencing a progressive deterioration of the condition. A significant reduction in vitamin D concentration was observed following subtotal gastrectomy. In response, high-dose vitamin D supplementation was administered to the patient. Within one week of treatment, swallowing symptoms improved, enabling the consumption of a small amount of liquid food. By the second week, substantial swallowing and neck function improvements were evident. After one month, the patient regained the ability to straighten the neck while walking and consumed a regular diet despite persistent difficulties chewing hard food. CONCLUSIONS: This case underscores the therapeutic potential of vitamin D in alleviating MG symptoms, particularly in individuals with compromised vitamin D levels following gastrectomy. The observed improvements present a new perspective on the possible involvement of vitamin D supplementation in the management of postoperative MG cases.


Asunto(s)
Gastrectomía , Miastenia Gravis , Vitamina D , Humanos , Gastrectomía/efectos adversos , Miastenia Gravis/cirugía , Miastenia Gravis/tratamiento farmacológico , Vitamina D/uso terapéutico , Vitamina D/administración & dosificación , Neoplasias Gástricas/cirugía , Masculino , Femenino , Anciano , Persona de Mediana Edad , Suplementos Dietéticos
7.
Artículo en Inglés | MEDLINE | ID: mdl-38842227

RESUMEN

BACKGROUND: Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis. OBJECTIVES: To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy. METHODS: Thirty-two-year Retrospective Multicenter Cohort Study of 265 patients with histologically diagnosed PSCC at three tertiary care centres. Predictive models based on patient or tumour characteristics were developed. RESULTS: Local recurrence occurred in 56 patients, metastasis in 52 patients and DSD in 40 patients. In multivariable models, the following five factors were independent prognostic factors based on subhazard ratio (SHR): history of balanitis (LR SHR: 2.3; 95% CI 1.2-4.2), poor differentiation (metastasis SHR 1.9; 95% CI 1.0-3.6), invasion into the corpora (metastasis SHR: 3.0; 95% CI 1.5-5.8 and DSD SHR: 4.5; 95% CI 1.7-12.1), perineural invasion (PNI) (metastasis SHR: 2.8; 95% CI 1.4-5.5 and DSD SHR: 3.5; 95% CI, 1.6-7.8) and a history of phimosis (DSD SHR: 2.5; 95% CI 1.2-5.3). The 5-year cumulative incidence of metastasis was higher for tumours with PNI [cumulative incidence function (CIF) = 55%, 95% CI 38-75 vs. CIF 15%, 95% CI 11-22], corporal invasion (CIF: 35%, 95% CI 26-47 vs. 12%, 95% CI 7-19) and poorly differentiated tumours (CIF = 46%, 95% CI 31-64 vs. CIF 15%, 95% CI 11-22). CONCLUSIONS: History of balanitis, history of phimosis, PNI, corporal invasion and poor differentiation are independent risk factors associated with poor outcomes. Since poor differentiation and PNI currently constitute only T1b disease, prognostic staging can likely be improved.

8.
Biomed Chromatogr ; : e5931, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38881185

RESUMEN

As a result of the lack of modern techniques, the study of Tibetan medicine has been hindered in identifying bioactive compounds. Herein, we established a chromatographic approach using an immobilized angiotensin II type 1 receptor (AT1R) via a one-step method triggered by haloalkane dehalogenase. The bioactive compounds from Choerospondias axillaris (Guangzao) were screened and identified using the immobilized AT1R followed by MS. Frontal analysis (FA) and adsorption energy distribution (AED) were used to evaluate the association constants. Molecular docking was used to investigate the binding configurations, and the surface efficiency index, binding efficiency index, and ligand-lipophilicity efficiency (LLE) were calculated to assess the drug-like properties. The results identified naringenin, pinocembrin, and chrysin as the compounds that specifically bind to AT1R in Guangzao. FA and AED confirmed that there is only one type of binding site between these compounds and AT1R. The association constants were (2.40 ± 0.02) × 104 M-1 for naringenin (5.22 ± 0.26) × 104 M-1 for pinocembrin, and (4.27 ± 0.14) × 104 M-1 for chrysin, respectively. These compounds can bind with AT1R through the orthosteric binding pocket. Naringenin exhibited better LLE than pinocembrin and chrysin. These results confirmed the feasibility of using the immobilized AT1R column for screening and analyzing bioactive compounds in Tibetan medicines.

9.
Chin Med Sci J ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38773789

RESUMEN

Vertebral artery dissection is a rare pathology that causes ischemic stroke in young people. Cervical massage, especially improper pulling manipulation, is a cause of vertebral artery dissection. We present a case of 32-year-old woman who developed acute multiple posterior circulation ischemic cerebral infarctions as a result of left vertebral artery V4 segment dissection after receiving neck massage. She underwent emergency vertebral artery stent implantation at the site of the dissection. Symptoms were relieved the day after treatment. The patient recovered without adverse complications or endovascular restenosis in the following year.

10.
Zhongguo Zhong Yao Za Zhi ; 49(2): 471-486, 2024 Jan.
Artículo en Zh | MEDLINE | ID: mdl-38403323

RESUMEN

This study combined network pharmacology, molecular docking, and in vitro experiments to explore the potential mechanism of the active components of the n-butanol fraction of Wenxia Formula(NWXF) combined with gefitinib(GEF) in treating non-small cell lung cancer(NSCLC). Ultra-performance liquid chromatography-quadrupole Orbitrap mass spectrometry(UPLC-Q-Orbitrap MS) was employed to detect the main chemical components of NWXF. The active components of NWXF were retrieved from SwissADME, and the candidate targets of these active components were retrieved from SwissTargetPrediction. Online Mendelian Inheritance in Man(OMIM) and GeneCards were searched for the targets of NSCLC. Cytoscape 3.9.0 and STRING were employed to build the protein-protein interaction(PPI) network with the common targets shared by NWXF and NSCLC. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment were performed in DAVID to predict the potential mechanisms. Finally, molecular docking between the main active ingredients and key targets was conducted in SYBYL-X 2.0. The methyl thiazolyl tetrazolium(MTT) assay was employed to evaluate the inhibitory effects of NWXF and/or GEF on the proliferation of human non-small cell lung cancer cells(A549 and PC-9). Additionally, the impact of NWXF on human embryonic lung fibroblast cells(MRC-5) was assessed. The effectiveness of the drug combination was evaluated based on the Q value. The terminal-deoxynucleoitidyl transferase mediated nick-end labeling(TUNEL) assay was employed to examine the apoptosis of A549 and PC-9 cells treated with NWXF and/or GEF. Quantitative real-time PCR(qRT-PCR) was employed to measure the mRNA levels of epidermal growth factor receptor(EGFR), c-Jun N-terminal kinase(JNK), and Bcl2-associated X protein(Bax) in the A549 and PC-9 cells treated with NWXF and/or GEF. Western blot was employed to determine the protein levels of EGFR, p-EGFR, JNK, p-JNK, and Bax in the A549 and PC-9 cells treated with NWXF and/or GEF. A total of 77 active components, 488 potential targets, and 49 key targets involved in the treatment of NSCLC with NWXF were predicted. The results of GO annotation showed that NWXF may treat NSCLC by regulating the biological processes such as cell proliferation, apoptosis, and protein phosphorylation. KEGG enrichment revealed that the key targets of NWXF in treating NSCLC were enriched in the mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT), hypoxia-inducible factor-1(HIF-1), and microRNA-related signaling pathways. Molecular docking results showed that 91.9% of the docking scores were greater than 5, indicating the strong binding capability between main active components and key targets. The cell experiments demonstrated that NWXF combined with GEF synergistically inhibited the proliferation, promoted the apoptosis, decreased p-EGFR/EGFR and p-JNK/JNK values, down-regulated the mRNA levels of EGFR and JNK, and up-regulated the mRNA and protein levels of Bax in A549 and PC-9 cells. In conclusion, NWXF combined with GEF can regulate the EGFR/JNK pathway to promote the apoptosis of NSCLC cells, thus treating NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Medicamentos Herbarios Chinos , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Gefitinib/farmacología , 1-Butanol , Proteína X Asociada a bcl-2 , Farmacología en Red , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB , ARN Mensajero , Medicamentos Herbarios Chinos/farmacología
11.
Small ; 19(6): e2205970, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36453593

RESUMEN

Herein, an efficient method to prepare sulfonated polyether ether ketone (SPEEK) based cation exchange membranes (CEMs) is developed, where polyethersulfone (PES) is used as an additive. The optimized membrane of 30 wt.%PES/SPEEK-M exhibits a rather low anion permeability and a high ionic conductivity of 9.52 mS cm-1 together with low volume swelling in water. Meanwhile, tensile strength of the membrane is as high as 31.4 MPa with a tensile strain of 162%. As separators for aqueous K-ion batteries (AKIBs) with decoupled gel electrolytes (Zn anode in alkaline and Prussian blue (FeHCF) cathode in neutral). Discharge voltage of the AKIB can reach 2.3 V. Meanwhile, Zn dendrites can be effectively suppressed in the gel anolyte. Specific capacities of the FeHCF cathode are 116.7 mAh g-1 at 0.3 A g-1 (close to its theoretical value), and 95.0 mAh g-1 at 1.0 A g-1 , indicating good rate performance. Capacity retention of the cathode is as high as 91.2% after 1000 cycles' cycling owing to the well remained neutral environment of the catholyte. There is almost no pH change for the catholyte after cycling, indicating good anion-blocking or cation-selecting ability of the 30 wt.%PES/SPEEK-M, much better than other membranes.

12.
Cancer Causes Control ; 34(1): 69-79, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36244051

RESUMEN

OBJECTIVE: Primary liver tumors are rare pediatric malignancies. Knowledge of the epidemiology of pediatric liver tumors is limited. This study aims to present the national incidence trends of pediatric liver tumors over 18 years, according to sociodemographic and histological subtype variation. METHODS: The Surveillance, Epidemiology, and End Results registry was queried from 2000 to 2017 for 1,099 patients between ages 0 and 19 with liver tumors. Age-standardized incidence rates by age, sex, and race/ethnicity were examined among histological subtypes. Annual percentage change (APC) was calculated via joinpoint regression for various sociodemographic and histotype subgroups. RESULTS: An increase of age-adjusted incidence rate of pediatric hepatic cancers was observed between 2000 and 2017 (APC, 1.7% [95% confidence interval or CI: 0.6%-2.8%], p-value = 0.006), which may likely attribute to the increasing incidence of hepatoblastoma and mesenchymal tumors (APC, 2.5% [95% CI: 1.1%-3.8%], p-value = 0.001). The incidence trend of hepatocellular carcinoma remained stable in the study period. The non-Hispanic Asian/Pacific Islander children and adolescents had a higher risk of hepatic tumors (incidence rate ratio or IRR, 1.42 [95% CI: 1.16-1.72], p-value = 0.0007) when compared with the non-Hispanic white subgroup, while a non-Hispanic black child was associated with a lower incidence rate (IRR, 0.64 [95% CI: 0.50-0.80], p-value < 0.0001). Significantly lower hepatic tumor incidence occurred in females than males, with an incidence rate ratio of 0.69 (95% CI: 0.61-0.78; p-value < 0.0001). Hepatic tumor incidence was also significantly lower in those aged 1-4 years (IRR, 0.47 [95% CI: 0.40-0.54]; p-value < 0.001) and 5-19 years (IRR, 0.09 [95% CI: 0.08-0.10]; p-value < 0.001) when compared with the youngest age group aged less than 1 year. These significant differences were also detected for the subgroup of hepatoblastoma and mesenchymal liver tumors but less among hepatocellular carcinomas (all p-values less than 0.0001). CONCLUSION: Continued increasing incidence of pediatric hepatoblastoma and mesenchymal liver tumors was discovered and warranted further investigation. Additional findings include a lower incidence of hepatic cancer among non-Hispanic black individuals and higher incidence of hepatic cancer in non-Hispanic Asian/Pacific Islander, male, and aged 1-4-year children and adolescents.


Asunto(s)
Carcinoma Hepatocelular , Hepatoblastoma , Neoplasias Hepáticas , Femenino , Niño , Humanos , Estados Unidos/epidemiología , Masculino , Adolescente , Incidencia , Hepatoblastoma/epidemiología , Datos de Salud Recolectados Rutinariamente , Programa de VERF , Neoplasias Hepáticas/epidemiología
13.
Inorg Chem ; 62(33): 13293-13303, 2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37557894

RESUMEN

The reprocessing of spent nuclear fuel is critical for the sustainability of the nuclear energy industry. However, several key separation processes present challenges in this regard, calling for continuous research into next-generation separation materials. Herein, we propose a high-throughput screening framework to improve efficiency in identifying potential ligands that selectively coordinate metal cations of interest in liquid wastes that considers multiple key chemical characteristics, including aqueous solubility, pKa, and coordination bond length. Machine-learning models were designed for the fast and accurate prediction of these characteristics by using graph convolution and transfer-learning techniques. Suitable ligands for Cs/Sr crystallizing separation were identified through the "computational funnel", and several top-ranking, nontoxic, low-cost ligands were selected for experimental verification.

14.
Acta Pharmacol Sin ; 44(8): 1600-1611, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36973542

RESUMEN

Epilepsy is one common brain disorder, which is not well controlled by current pharmacotherapy. In this study we characterized the therapeutic potential of borneol, a plant-derived bicyclic monoterpene compound, in the treatment of epilepsy and elucidated the underlying mechanisms. The anti-seizure potency and properties of borneol were assessed in both acute and chronic mouse epilepsy models. Administration of (+)-borneol (10, 30, 100 mg/kg, i.p.) dose-dependently attenuated acute epileptic seizure in maximal-electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models without obvious side-effect on motor function. Meanwhile, (+)-borneol administration retarded kindling-induced epileptogenesis and relieved fully kindled seizures. Importantly, (+)-borneol administration also showed therapeutic potential in kainic acid-induced chronic spontaneous seizure model, which was considered as a drug-resistant model. We compared the anti-seizure efficacy of 3 borneol enantiomers in the acute seizure models, and found (+)-borneol being the most satisfying one with long-term anti-seizure effect. In electrophysiological study conducted in mouse brain slices containing the subiculum region, we revealed that borneol enantiomers displayed different anti-seizure mechanisms, (+)-borneol (10 µM) markedly suppressed the high frequency burst firing of subicular neurons and decreased glutamatergic synaptic transmission. In vivo calcium fiber photometry analysis further verified that administration of (+)-borneol (100 mg/kg) inhibited the enhanced glutamatergic synaptic transmission in epilepsy mice. We conclude that (+)-borneol displays broad-spectrum anti-seizure potential in different experimental models via decreasing the glutamatergic synaptic transmission without obvious side-effect, suggesting (+)-borneol as a promising anti-seizure compound for pharmacotherapy in epilepsy.


Asunto(s)
Epilepsia , Excitación Neurológica , Ratones , Animales , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Canfanos/uso terapéutico , Canfanos/farmacología , Excitación Neurológica/fisiología , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Modelos Animales de Enfermedad
15.
J Sep Sci ; 46(9): e2200944, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36820791

RESUMEN

As a famous traditional Chinese formula, Danshen Decoction has the potential to relieve the pain of pulmonary arterial hypertension patients, however, the functional components remain unknown. Herein, we reported a method to screen the functional components in Danshen Decoction targeting endothelin receptor A, an accepted target for the treatment of the disease. The receptor was functionalized on the macroporous silica gel through an epidermal growth factor receptor fusion tag and its covalent inhibitor. Using the affinity gel as the stationary phase, the bioactive compound was identified as salvianolic acid B by mass spectrometry. The binding kinetic parameter (dissociation rate constants kd ) of salvianolic acid B with the receptor was determined via peak profiling. Using the specific ligands of the receptor as probes, the binding configuration prediction of salvianolic acid B with the receptor was performed by molecular dynamics simulation. Our results indicated that salvianolic acid B is a potential bioactive compound in Danshen Decoction targeting the receptor. This work showed that receptor chromatography in combination with molecular dynamics simulation is applicable to predicting the binding kinetics and configuration of a ligand to a receptor, providing crucial insight for the rational design of drugs that recognize functional proteins.


Asunto(s)
Medicamentos Herbarios Chinos , Salvia miltiorrhiza , Humanos , Salvia miltiorrhiza/química , Receptor de Endotelina A , Simulación de Dinámica Molecular , Medicamentos Herbarios Chinos/química , Cromatografía de Afinidad , Cromatografía Líquida de Alta Presión/métodos
16.
Clin Exp Dermatol ; 48(4): 319-324, 2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36662541

RESUMEN

Atopic dermatitis (AD) is a common, chronic skin disorder that is associated with dysbiosis of the skin microbiome along with an impaired skin barrier and abnormal immune signalling. Particularly, AD has been associated with increased abundance of Staphylococcus aureus and decreased overall bacterial diversity. Topical probiotic formulations are garnering further interest in the treatment of AD and may be derived from commensal bacteria found on healthy epithelium or from exogenous bacteria. Strains chosen for clinical trials have often demonstrated antimicrobial actions to S. aureus in vitro. Multiple randomized clinical trials with topical probiotics have resulted in significant improvements in clinical severity, decreased abundance of S. aureus in treated lesional skin and increased bacterial diversity. Side-effects from available studies have been minimal apart from one patient who developed a furuncle in the treatment area. Topical probiotics have been shown to be safe and potentially efficacious in AD; however, further research including larger, longer-term clinical trials need to be performed before topical probiotics should be recommended to patients.


Asunto(s)
Dermatitis Atópica , Probióticos , Humanos , Dermatitis Atópica/tratamiento farmacológico , Staphylococcus aureus , Piel/microbiología , Probióticos/uso terapéutico , Epitelio
17.
Ecotoxicol Environ Saf ; 253: 114705, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36863159

RESUMEN

Deoxynivalenol (DON), as a widespread Fusarium mycotoxin in cereals, food products, and animal feed, is detrimental to both human and animal health. The liver is not only the primary organ responsible for DON metabolism but also the principal organ affected by DON toxicity. Taurine is well known to display various physiological and pharmacological functions due to its antioxidant and anti-inflammatory properties. However, the information regarding taurine supplementation counteracting DON-induced liver injury in piglets is still unclear. In our work, twenty-four weaned piglets were subjected to four groups for a 24-day period, including the BD group (a basal diet), the DON group (3 mg/kg DON-contaminated diet), the DON+LT group (3 mg/kg DON-contaminated diet + 0.3% taurine), and the DON+HT group (3 mg/kg DON-contaminated diet + 0.6% taurine). Our findings indicated that taurine supplementation improved growth performance and alleviated DON-induced liver injury, as evidenced by the reduced pathological and serum biochemical changes (ALT, AST, ALP, and LDH), especially in the group with the 0.3% taurine. Taurine could counteract hepatic oxidative stress in piglets exposed to DON, as it reduced ROS, 8-OHdG, and MDA concentrations and improved the activity of antioxidant enzymes. Concurrently, taurine was observed to upregulate the expression of key factors involved in mitochondrial function and the Nrf2 signaling pathway. Furthermore, taurine treatment effectively attenuated DON-induced hepatocyte apoptosis, as verified through the decreased proportion of TUNEL-positive cells and regulation of the mitochondria-mediated apoptosis pathway. Finally, the administration of taurine was able to reduce liver inflammation due to DON, by inactivating the NF-κB signaling pathway and declining the production of pro-inflammatory cytokines. In summary, our results implied that taurine effectively improved DON-induced liver injury. The underlying mechanism should be that taurine restored mitochondrial normal function and antagonized oxidative stress, thereby reducing apoptosis and inflammatory responses in the liver of weaned piglets.


Asunto(s)
Antioxidantes , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Animales , Humanos , Porcinos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Taurina/farmacología , Taurina/uso terapéutico , Taurina/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Hígado , Estrés Oxidativo , Inflamación/metabolismo , Suplementos Dietéticos , Apoptosis , Mitocondrias/metabolismo , Alimentación Animal/análisis
18.
Chem Biodivers ; 20(1): e202200999, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36484459

RESUMEN

Five unknown labdane diterpenoids Stevelins A-E (1-5), three known labdane diterpenoids (6-8) and three labdane norditerpenoids (9-11) were isolated from the Stevia rebaudiana. The structures were determined primarily via NMR spectroscopic data and HR-ESI-MS experiments. X-ray crystallography using CuKα radiation was used to determine the absolute configurations of 1, and the absolute configurations of 2-5 were deduced by electronic circular dichroism (ECD) calculations. The potential anti-atherosclerosis activities of all compounds were evaluated by measuring their inhibitory effects on the macrophage foam cell formation. As a result, most isolated compounds could significantly inhibit oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation, which suggests that these compounds may be promising candidates in the treatment for atherosclerosis.


Asunto(s)
Diterpenos , Stevia , Estructura Molecular , Diterpenos/farmacología , Diterpenos/química , Espectroscopía de Resonancia Magnética , Dicroismo Circular
19.
Cancer Causes Control ; 33(5): 687-699, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35192107

RESUMEN

OBJECTIVE: To characterize the epidemiological trends and sociodemographic variation of pediatric and adolescent neurological cancers by histological subtypes over time in the USA. METHODS: A total of 16,511 patients aged 0-19 years diagnosed with neurological cancers between 2000 and 2018, including 13,024 with central nervous system (CNS) neoplasms and 3,487 with neuroblastomas, were identified from 18 registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Incidence trends over time and incidence rate ratios by race/ethnicity, sex, and age were calculated for histological subtype. Age-standardized incidence rates (ASIR) by year of diagnosis and average annual percent changes (AAPC) were calculated to measure incidence rates. ASIR by race/ethnicity, sex, and age were calculated to examine the incidence variation by these factors. RESULTS: Overall, age-standardized annual incidence per 100,000 person-years increased from 2.20 in 2000 to 3.21 in 2018 with an AAPC of 1.4% (95% confidence interval or CI: 0.5% to 2.4%); however, that of Hispanic decreased from 2.93 in 2000 to 2.59 in 2018 with an AAPC of - 0.8% (95% CI: - 1.2% to - 0.3%). Non-Hispanic Black children and adolescents had a statistically significantly lower incidence than non-Hispanic White peers both for CNS neoplasms (incidence rate ratio or IRR: 0.67; 95% CI: 0.63 to 0.71) and neuroblastomas (IRR: 0.75; 95% CI: 0.68 to 0.83). Females generally had a lower incidence than males, especially among those with intracranial and intraspinal embryonal tumors (IRR: 0.69; 95% CI: 0.64 to 0.75). The highest incidence rate of neuroblastoma was among newborns aged less than 1 year, and the highest incidence rate of CNS neoplasms was among children aged 1-4 years. CONCLUSION: The incidence of neurological cancers has increased among children and adolescents from 2000 to 2018, with wide variation across demographic groups.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Neuroblastoma , Adolescente , Neoplasias del Sistema Nervioso Central/epidemiología , Niño , Etnicidad , Femenino , Humanos , Incidencia , Recién Nacido , Masculino , Sistema de Registros , Programa de VERF , Estados Unidos/epidemiología
20.
Chem Rec ; 22(10): e202200114, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35785428

RESUMEN

Aqueous zinc-ion batteries (ZIBs) have attracted widespread attention due to the intrinsic features of Zn-based anodes, mainly including high capacity, low cost, and low working potential together with high over-potential for hydrogen evolution reaction. Aqueous ZIBs are considered to be strong competitors and substitutes for lead-acid, nickel-metal hydrogen, nickel-cadmium, and even lithium-ion batteries. Great efforts have been made in the past few years towards the issues existed in aqueous ZIBs, mainly including alkaline and mild acidic systems. In this perspective, we illustrate the advantages, the main challenges, and the corresponding solution strategies of Zn-based anodes in various aqueous rechargeable ZIBs with alkaline and mild acidic electrolytes. Furthermore, feasible aqueous ZIBs for practical use are prospected.

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