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1.
Addict Biol ; 29(3): e13382, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38488467

RESUMEN

Methamphetamine (METH) is a highly addictive psycho-stimulant that induces addictive behaviour by stimulating increased dopamine release in the nucleus accumbens (NAc). The sarco/endoplasmic reticulum calcium ion transport ATPases (SERCA or ATP2A) is a calcium ion (Ca2+) pump in the endoplasmic reticulum (ER) membrane. SERCA2b is a SERCA subtype mainly distributed in the central nervous system. This study used conditioned place preference (CPP), a translational drug reward model, to observe the effects of SERCA and SERCA2b on METH-CPP in mice. Result suggested that the activity of SERCA was significantly decreased in NAc after METH-CPP. Intraperitoneal SERCA agonist CDN1163 injection or bilateral CDN1163 microinjection in the NAc inhibited METH-CPP formation. SERCA2b overexpression by the Adeno-associated virus can reduce the DA release of NAc and inhibit METH-CPP formation. Although microinjection of SERCA inhibitor thapsigargin in the bilateral NAc did not significantly aggravate METH-CPP, interference with SERCA2b expression in NAc by adeno-associated virus increased DA release and promoted METH-CPP formation. METH reduced the SERCA ability to transport Ca2+ into the ER in SHSY5Y cells in vitro, which was reversed by CDN1163. This study revealed that METH dysregulates intracellular calcium balance by downregulating SERCA2b function, increasing DA release in NAc and inducing METH-CPP formation. Drugs that target SERCA2b may have the potential to treat METH addiction.


Asunto(s)
Benzamidas , Estimulantes del Sistema Nervioso Central , Metanfetamina , Ratones , Animales , Metanfetamina/farmacología , Metanfetamina/metabolismo , Núcleo Accumbens , Calcio/metabolismo , Aminoquinolinas/metabolismo , Aminoquinolinas/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Estimulantes del Sistema Nervioso Central/metabolismo
2.
Eur Spine J ; 33(1): 216-223, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37715791

RESUMEN

OBJECTIVES: To determine the predictive effect of Hounsfield unit (HU) values in the cervical vertebral body measured by computed tomography (CT) and T-scores measured by dual-energy X-ray absorptiometry (DXA) on Zero-P subsidence after anterior cervical discectomy and fusion (ACDF)with Zero-P. In addition, we evaluated the most reliable measurement of cervical HU values. METHODS: We reviewed 76 patients who underwent single-level Zero-P fusion for cervical spondylosis. HU values were measured on CT images according to previous studies. Univariate analysis was used to screen the influencing factors of Zero-P subsidence, and then, logistic regression was used to determine the independent risk factors. The area under the receiver operating characteristic curve (AUC) was used to evaluate the ability to predict Zero-P subsidence. RESULTS: Twelve patients (15.8%) developed Zero-P subsidence. There were significant differences between subsidence group and non-subsidence group in terms of age, axial HU value, and HU value of midsagittal, midcoronal, and midaxial (MSCD), but there were no significant differences in lowest T-score and lowest BMD. The axial HU value (OR = 0.925) and HU value of MSCD (OR = 0.892) were independent risk factors for Zero-P subsidence, and the lowest T-score was not (OR = 1.186). The AUC of predicting Zero-P subsidence was 0.798 for axial HU value, 0.861 for HU value of MSCD, and 0.656 for T-score. CONCLUSIONS: Lower cervical HU value indicates a higher risk of subsidence in patients following Zero-P fusion for single-level cervical spondylosis. HU values were better predictors of Zero-P subsidence than DXA T-scores. In addition, the measurement of HU value in the midsagittal, midcoronal, and midaxial planes of the cervical vertebral body provides an effective method for predicting Zero-P subsidence.


Asunto(s)
Fusión Vertebral , Espondilosis , Humanos , Absorciometría de Fotón/métodos , Tomografía Computarizada por Rayos X/métodos , Discectomía , Curva ROC , Espondilosis/diagnóstico por imagen , Espondilosis/cirugía , Estudios Retrospectivos , Fusión Vertebral/métodos , Vértebras Lumbares
3.
Molecules ; 29(4)2024 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-38398577

RESUMEN

In the relentless pursuit of innovative therapeutic agents, natural products have emerged as a transformative avenue in the battle against infectious diseases [...].


Asunto(s)
Antifúngicos , Productos Biológicos , Antifúngicos/farmacología , Productos Biológicos/farmacología , Antibacterianos/farmacología , Antivirales/farmacología
4.
Oncologist ; 28(6): 501-509, 2023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-36866412

RESUMEN

BACKGROUND: Lenvatinib plus pembrolizumab showed significantly improved progression-free and overall survival outcomes compared with sunitinib in patients with advanced renal cell carcinoma in the CLEAR study (NCT02811861). Here, we used CLEAR data to characterize common adverse reactions (ARs; adverse-event preferred terms grouped in accordance with regulatory authority review) associated with lenvatinib plus pembrolizumab and review management strategies for select ARs. MATERIALS AND METHODS: Safety data from the 352 patients who received lenvatinib plus pembrolizumab in the CLEAR study were analyzed. Key ARs were chosen based on frequency of occurrence (≥30%). Time to first onset and management strategies for key ARs were detailed. RESULTS: The most frequent ARs were fatigue (63.1%), diarrhea (61.9%), musculoskeletal pain (58.0%), hypothyroidism (56.8%), and hypertension (56.3%); grade ≥3 severity ARs that occurred in ≥5% of patients were hypertension (28.7%), diarrhea (9.9%), fatigue (9.4%), weight decreased (8.0%), and proteinuria (7.7%). Median times to first onset of all key ARs were within approximately 5 months (approximately 20 weeks) of starting treatment. Strategies for effectively managing ARs included baseline monitoring, drug-dose modifications, and/or concomitant medications. CONCLUSION: The safety profile of lenvatinib plus pembrolizumab was consistent with the known profile of each monotherapy; ARs were considered manageable with strategies including monitoring, dose modifications, and supportive medications. Proactive and prompt identification and management of ARs are important for patient safety and to support continued treatment. CLINICALTRIALS.GOV ID: NCT02811861.


Asunto(s)
Carcinoma de Células Renales , Hipertensión , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Compuestos de Fenilurea/efectos adversos , Neoplasias Renales/patología , Fatiga/inducido químicamente , Diarrea/inducido químicamente , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
5.
Bioorg Chem ; 140: 106797, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37647807

RESUMEN

Miliusanes are a class of anticancer lead molecules belonging to meroterpenoids with an 18-carbon skeleton isolated from Miliusa plants. A phytochemical study of the plant M. sinensis was carried out to discover new miliusanes with diverse structural features in order to better understand their structure-activity relationship. As a result, 20 compounds including 12 new ones (7-14 and 17-20) belonging to two sub-classes of miliusanes were isolated and identified from the twigs and leaves of this plant. Their structures, including absolute configurations, were determined by spectroscopic analyses and electronic circular dichroism. The absolute stereochemistry of miliusane structures has also been confirmed for the first time through the single crystal X-ray diffraction analysis of miliusol (1). Bioactivity evaluation showed that some of the miliusane isolates potently inhibit cell growth of several human derived cancer cell lines with IC50 values ranging from 0.52 to 23.5 µM. Compound 11 demonstrated more potent cytotoxic activity than the known miliusol (1) in stomach cancer cells though its structure contains an unconjugated 1, 4-diketone system, which added a new structure-activity feature to miliusanes. The preliminary mechanism of action studies revealed that they could be a class of dual cell migration inhibitor and senescence inducer.


Asunto(s)
Annonaceae , Humanos , Carbono , Ciclo Celular , Línea Celular
6.
Molecules ; 28(21)2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-37959740

RESUMEN

This study explores the antifungal properties of Agaricus blazei Murrill, a valuable medicinal and edible fungus. Six compounds (1-6) were first isolated from A. blazei using various isolation techniques and identified using spectroscopic methods. These compounds include linoleic acid, 1,1'-oxybis(2,4-di-tert-butylbenzene), glycerol monolinoleate, volemolide (17R)-17-methylincisterol, (24s)-ergosta-7-en-3-ol, and dibutyl phthalate. This study also assesses the antifungal activities of these compounds against Trichophyton mentagrophology, Trichophyton rubrum, Candida albicans, and Cryptococcus neoformans. The results demonstrate varied sensitivities against these pathogenic fungi, with compound 2 showing significant inhibition against T. mentagrophology, compound 3 showing significant inhibition against T. rubrum, and compound 6 showing significant inhibition against C. albicans. This study underscores the medicinal potential of A. blazei as an antifungal agent and sheds light on its valuable research implications.


Asunto(s)
Agaricus , Antifúngicos , Antifúngicos/farmacología , Agaricus/química , Candida albicans , Trichophyton
7.
Molecules ; 28(14)2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37513270

RESUMEN

The activation of innate antiviral immunity is a promising approach for combatting viral infections. In this study, we screened Chinese herbs that activated human immunity and identified coptisine as a potent inhibitor of the influenza virus with an EC50 of 10.7 µM in MDCK cells. The time of an addition assay revealed that pre-treatment with coptisine was more effective at reducing viral replication than co-treatment or post-treatment. Our bulk RNA-sequencing data showed that coptisine upregulated the p21 signaling pathway in MDCK cells, which was responsible for its antiviral effects. Specifically, coptisine increased the expression of p21 and FOXO1 in a dose-dependent manner while leaving the MELK expression unchanged. Docking analysis revealed that coptisine likely inhibited MELK activity directly by forming hydrogen bonds with ASP-150 and GLU-87 in the catalytic pocket. These findings suggest that coptisine may be a promising antiviral agent that regulates the p21 signaling pathway to inhibit viral replication.


Asunto(s)
Berberina , Gripe Humana , Humanos , Gripe Humana/tratamiento farmacológico , Antivirales/farmacología , Antivirales/uso terapéutico , Berberina/farmacología , Replicación Viral , Proteínas Serina-Treonina Quinasas
8.
Molecules ; 27(20)2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36296430

RESUMEN

In order to discover more promising antifungal and antibacterial agents, a series of new derivatives were designed and synthesized by structure modification based on the naturally occurring antimicrobial compound lophanic acid. The structures of all the target compounds were well characterized by spectroscopic data. The stereochemistry of these compounds was further determined through the X-ray diffraction analysis of 6a. The synthetic compounds were evaluated for their antimicrobial activities against filamentous fungi (T. rubrum, T. mentagrophytes), yeasts (C. neoformans, C. albicans) and Gram-positive and Gram-negative bacteria (MRSA, S. mutans, S. sobrinus, and E. coli). Among them, 3d and 3i are found as the most promising leads that showed potent inhibitory effects against all the tested fungal and bacterial strains except for E. coli. The presence of the C-20 carboxylic ester groups and the free hydroxy group at C-13 was found to be essential for the antifungal and antibacterial activities of the lophanic acid derivatives.


Asunto(s)
Antiinfecciosos , Antifúngicos , Antifúngicos/química , Antibacterianos/química , Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Bacterias Grampositivas , Escherichia coli , Relación Estructura-Actividad , Hongos , Candida albicans , Antiinfecciosos/farmacología , Ésteres/farmacología , Estructura Molecular
9.
Molecules ; 27(5)2022 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35268699

RESUMEN

Previous studies have reported that recombinant tumor necrosis factor (TNF)-α has powerful antiviral activity but severe systematic side effects. Jasminin is a common bioactive component found in Chinese herbal medicine beverage "Jasmine Tea". Here, we report that jasminin-induced endogenous TNF-α showed antiviral activity in vitro. The underlying TNF-α-inducing action of jasminin was also investigated in RAW264.7 cells. The level of endogenous TNF-α stimulated by jasminin was first analyzed by an enzyme-linked immunosorbent assay (ELISA) from the cell culture supernatant of RAW264.7 cells. The supernatants were then collected to investigate the potential antiviral effect against herpes simplex virus 1 (HSV-1). The antiviral effects of jasminin alone or its supernatants were evaluated by a plaque reduction assay. The potential activation of the PI3K-Akt pathway, three main mitogen-activated protein kinases (MAPKs), and nuclear factor (NF)-κB signaling pathways that induce TNF-α production were also investigated. Jasminin induces TNF-α protein expression in RAW264.7 cells without additional stimuli 10-fold more than the control. No significant up-expression of type I, II, and III interferons; interleukins 2 and 10; nor TNF-ß were observed by the jasminin stimuli. The supernatants, containing jasminin-induced-TNF-α, showed antiviral activity against HSV-1. The jasminin-stimulated cells caused the simultaneous activation of the Akt, MAPKs, and NF-κB signal pathways. Furthermore, the pretreatment of the cells with the Akt, MAPKs, and NF-κB inhibitors effectively suppressed jasminin-induced TNF-α production. Our research provides evidence that endogenous TNF-α can be used as a strategy to encounter viral infections. Additionally, the Akt, MAPKs, and NF-κB signaling pathways are involved in the TNF-α synthesis that induced by jasminin.


Asunto(s)
Fosfatidilinositol 3-Quinasas , Factor de Necrosis Tumoral alfa , Antivirales/farmacología , Lipopolisacáridos/farmacología , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
10.
Molecules ; 25(4)2020 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-32093422

RESUMEN

Edible mushrooms are an important source of nutraceuticals and for the discovery of bioactive metabolites as pharmaceuticals. In this work, the OSMAC (One Strain, Many Active Compounds) approach was used to isolate two new compounds (1 and 2) along with seven known compounds (3-9) from a mycelial culture of a unique North American edible mushroom Hericium sp. The fruiting body was collected in Marine on St. Croix, Minnesota (USA), and mycelial cultures were grown on four different solid and liquid media. Extracts from the mycelial cultures were screened for antimicrobial activity and only the extract from the Cheerios substrate culture exhibited antifungal activity. Bioassay guided fractionation and HPLC analysis were used to isolate nine pure compounds and the structures of the known compounds were established by analysis of the NMR and mass spectrometry data and comparison to published reports. Compound 1 is a new erinacerin alkaloid and 2 is an aldehyde derivative of 4-hydroxy chroman. Four chlorinated orcinol derivatives (3-6), a pyran (7), erinaceolactone (8), and erinacine (9) were identified. Compound 4 showed antifungal activity against C. albicans and C. neoformans (MIC = 31.3-62.5 µg/mL, respectively). Compound 4 also inhibited biofilm formation of C. albicans and C. neoformans at 7.8 µg/mL. These results suggest that mycelial cultures of edible fungi may provide useful, bioactive compounds.


Asunto(s)
Agaricales/química , Antifúngicos , Candida albicans/crecimiento & desarrollo , Micelio/química , Agaricales/crecimiento & desarrollo , Antifúngicos/química , Antifúngicos/farmacología , Biopelículas , Micelio/crecimiento & desarrollo
11.
Molecules ; 23(12)2018 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-30563201

RESUMEN

The purpose of this research was to investigate the chemical profile, nutritional quality, antioxidant and hypolipidemic effects of Mexican chia seed oil (CSO) in vitro. Chemical characterization of CSO indicated the content of α-linolenic acid (63.64% of total fatty acids) to be the highest, followed by linoleic acid (19.84%), and saturated fatty acid (less than 11%). Trilinolenin content (53.44% of total triacylglycerols (TAGs)) was found to be the highest among seven TAGs in CSO. The antioxidant capacity of CSO, evaluated with ABTS•+ and DPPH• methods, showed mild antioxidant capacity when compared with Tocopherol and Catechin. In addition, CSO was found to lower triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C) levels by 25.8% and 72.9%respectively in a HepG2 lipid accumulation model. As CSO exhibits these chemical and biological characteristics, it is a potential resource of essential fatty acids for human use.


Asunto(s)
Fitoquímicos/química , Aceites de Plantas/química , Salvia/química , Antioxidantes/química , Ácidos Grasos/química , Células Hep G2 , Humanos , Fitoquímicos/metabolismo , Aceites de Plantas/metabolismo , Semillas/química , Triglicéridos , Ácido alfa-Linolénico/química
13.
Int J Mol Sci ; 16(11): 27978-87, 2015 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-26610490

RESUMEN

Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2).


Asunto(s)
Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Pteris/química , Fármacos Anti-VIH/envenenamiento , Antiinfecciosos/química , Antiinfecciosos/farmacología , Línea Celular , Diterpenos de Tipo Kaurano/aislamiento & purificación , VIH-1/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Extractos Vegetales/aislamiento & purificación
14.
Colloids Surf B Biointerfaces ; 234: 113724, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38183870

RESUMEN

Both ursolic acid (UA) and sorafenib (Sora) have been generally utilized in cancer treatment, and the combination of the two has also shown a good anti-tumor effect. However, single-agent therapy for Hepatocellular carcinoma (HCC) has the disadvantages of multi-drug resistance, poor water solubility and low bioavailability, and the application of traditional nanocarrier materials is limited due to their low drug loading and low carrier-related toxicity. Therefore, we prepared US NPs with different proportions of UA and Sora by solvent exchange method for achieving synergistic HCC therapy. US NPs had suitable particle size, good dispersibility and storage stability, which synergistically inhibited the proliferation of HepG2 cells, SMMC7721 cells and H22 cells. In addition, we also proved that US NPs were able to suppress the migration of HepG2 cells and SMMC7721 cells and reduce the adhesion ability and colony formation ability of these cells. According to the results, US NPs could degrade the membrane potential of mitochondrial, participate in cell apoptosis, and synergistically induce autophagy. Collectively, the carrier-free US NPs provide new strategies for HCC treatment and new ideas for the development of novel nano-drug delivery systems containing UA and Sora.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Humanos , Sorafenib/farmacología , Sorafenib/uso terapéutico , Carcinoma Hepatocelular/patología , Ácido Ursólico , Preparaciones Farmacéuticas , Neoplasias Hepáticas/patología , Línea Celular Tumoral
15.
J Colloid Interface Sci ; 656: 177-188, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-37989051

RESUMEN

The effectiveness of chemotherapeutic agents for hepatocellular carcinoma (HCC) is unsatisfactory because of tumor heterogeneity, multidrug resistance, and poor target accumulation. Therefore, multimodality-treatment with accurate drug delivery has become increasingly popular. Herein, a cell penetrating peptide-aptamer dual modified-nanocomposite (USILA NPs) was successfully constructed by coating a cell penetrating peptide and aptamer onto the surface of sorafenib (Sora), ursolic acid (UA) and indocyanine green (ICG) condensed nanodrug (USI NPs) via one-pot assembly for targeted and synergistic HCC treatment. USILA NPs showed higher cellular uptake and cytotoxicity in HepG2 and H22 cells, with a high expression of epithelial cell adhesion molecule (EpCAM). Furthermore, these NPs caused more significant mitochondrial membrane potential reduction and cell apoptosis. These NPs could selectively accumulate at the tumor site of H22 tumor-bearing mice and were detected with the help of ICG fluorescence; moreover, they retarded tumor growth better than monotherapy. Thus, USILA NPs can realize the targeted delivery of dual drugs and the integration of diagnosis and treatment. Moreover, the effects were more significant after co-administration of iRGD peptide, a tumor-penetrating peptide with better penetration promoting ability or programmed cell death ligand 1 (PD-L1) antibody for the reversal of the immunosuppressive state in the tumor microenvironment. The tumor inhibition rates of USILA NPs + iRGD peptide or USILA NPs + PD-L1 antibody with good therapeutic safety were 72.38 % and 67.91 % compared with control, respectively. Overall, this composite nanosystem could act as a promising targeted tool and provide an effective intervention strategy for enhanced HCC synergistic treatment.


Asunto(s)
Carcinoma Hepatocelular , Péptidos de Penetración Celular , Neoplasias Hepáticas , Nanopartículas , Ratones , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Preparaciones Farmacéuticas , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Péptidos de Penetración Celular/química , Antígeno B7-H1/uso terapéutico , Nanopartículas/química , Línea Celular Tumoral , Microambiente Tumoral
16.
J Ethnopharmacol ; 328: 118059, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38508430

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is characterized by hyperkeratosis that produces the classic silvery scales, and the pathogenesis of psoriasis involves abnormal proliferation of keratinocytes. Emerging evidence supports that apoptosis regulates keratinocyte proliferation and formation of stratum corneum, which maintains the homeostasis of the skin. Qinzhuliangxue mixture (QZLX) is a representative formula for the treatment of psoriasis, which was earliest recorded in the classic Chinese medicine book Xia's Surgery. In our previous clinical studies, QZLX demonstrated 83.33% efficacy with few side effects in the treatment of psoriasis. Furthermore, our published basic research has also proved that the QZLX mixture effectively inhibits the hyperproliferation of keratinocytes, thus exerting therapeutic effects on psoriasis. However, whether QZLX mixture can regulate keratinocytes apoptosis requires further clarification. OBJECTIVE OF THE STUDY: To investigate the mechanism of QZLX in the treatment of psoriasis from the perspective of keratinocyte apoptosis. MATERIALS AND METHODS: First, psoriasis-like mice with imiquimod (IMQ)-induced were given QZLX intragastric administration and Psoriasis Area Severity Index (PASI) scores were recored for 11 consecutive days to appraise the efficacy. Then, tissue samples were collected for transcriptome analysis. The DEseq2 method detected significantly differentially expressed genes (DEGs), Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway databases were used to analyze the functions and pathway enrichment of DEGs. After that, the therapeutic mechanisms of QZLX in intervening with psoriasis were explored using TUNEL, immunohistochemical staining, and western blotting. RESULTS: QZLX ameliorated the symptoms and pathological characteristics of IMQ-induced psoriasis in mice. The epidermal cell hyperplasia in the skin was inhibited, in accordance with the suppressed expression of PCNA and Ki67 after treatment. Transcriptome sequencing showed that melanoma differentiation associated gene-5 (MDA-5) was downregulated. GO and KEGG enrichment analysis of the signaling pathways indicated that the differentially expressed genes were significantly enriched in apoptosis pathways. Besides, QZLX treatment decreased the apoptosis of keratinocyte as shown by reduced TUNEL-positive cells. As MDA-5 protein levels decreased, so did the expression of the downstream protein Caspase-8, which indicates that the apoptotic pathway was triggered. Furthermore, QZLX therapy might also help to balance the apoptotic Bcl-2 family expression. CONCLUSION: QZLX restrains the apoptosis of keratinocyte in psoriasis-like mice by downregulating the MDA-5 pathway. The restoration of the balance between cell apoptosis and proliferation in the skin may lead to considerable psoriasis relief. Our study reveals the possible molecular processes behind the effects of QZLX therapy on the skin lesions of psoriasis, and lends support to its clinical efficacy.


Asunto(s)
Psoriasis , Enfermedades de la Piel , Animales , Ratones , Psoriasis/patología , Piel , Queratinocitos , Enfermedades de la Piel/metabolismo , Imiquimod , Proliferación Celular , Hiperplasia/patología , Apoptosis , Ratones Endogámicos BALB C , Modelos Animales de Enfermedad
17.
J Subst Use Addict Treat ; 156: 209189, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37866441

RESUMEN

INTRODUCTION: Methamphetamine use disorder (MUD) can cause impulsive behavior, anxiety, and depression. Stimulation of the left dorsolateral prefrontal cortex in MUD patients by intermittent theta burst repetitive transcranial magnetic stimulation (iTBS-rTMS) is effective in reducing cravings, impulsive behavior, anxiety, and depression. The purpose of this study was to explore whether these psychological factors helped to predict MUD patients' responses to iTBS-rTMS treatment. METHODS: Fifty MUD patients and sixty healthy subjects matched for general conditions were used as study subjects. The study randomly divided MUD patients into iTBS-rTMS and sham stimulation groups and received 20 sessions of real or sham iTBS-rTMS treatment, and the study collected cue-related evoked craving data before and after treatment. All subjects completed the Barratt Impulsiveness Scale (BIS-11), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: The MUD patients showed significantly higher levels of impulsivity, anxiety, and depression than the healthy subjects. The MUD patients who received the real treatment had significantly lower impulsivity, anxiety, and depression scores, and better treatment effects on cravings than the sham stimulation group. The Spearman rank correlation and stepwise multiple regression analyses showed that the baseline BIS-11 and the reduction rate (RR) of BIS-11 and RR of SDS were positively correlated with the decrease in cravings in the iTBS-rTMS group. ROC curve analysis showed that RR of SDS (AUC = 91.6 %; 95 % CI = 0.804-1.000) had predictive power to iTBS- rTMS therapeutic efficacy, the cutoff value is 15.102 %. CONCLUSIONS: iTBS-rTMS had a good therapeutic effect in MUD patients and the baseline impulsivity, the improved depression and impulsivity were associated with therapeutic effect of iTBS-rTMS. The improved depression had the potential to predict the efficacy of the iTBS-rTMS modality for MUD treatment.


Asunto(s)
Depresión , Estimulación Magnética Transcraneal , Humanos , Ansiedad/terapia , Depresión/terapia , Conducta Impulsiva , Ritmo Teta/fisiología
18.
Psychiatr Genet ; 33(2): 50-58, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36794980

RESUMEN

Prior studies have indicated the pathological role of brain-derived neurotrophic factor (BDNF) gene polymorphism in panic disorders (PD). A functionally less active BDNF Val66Met mutant was previously detected in PD patients with different ethnic backgrounds. However, the results remain inconclusive or inconsistent. A meta-analysis was used to explore the consistency of the BDNF Val66Met mutant's association with PD irrespective of the subject's ethnicity. Relevant case-controlled full-length clinical and preclinical reports were retrieved by database searching, and 11 articles involving 2203 cases and 2554 controls were systematically selected per the standard inclusion criteria. Eleven articles were finally included that explored the relationship between the Val66Met polymorphism and PD risk susceptibility. Statistical analysis revealed a significant genetic association of the mutation, allele frequencies, and genotype distributions of BDNF with PD onset. Our findings demonstrated that the BDNF Val66Met is a susceptibility factor of PD.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Trastorno de Pánico , Humanos , Factor Neurotrófico Derivado del Encéfalo/genética , Trastorno de Pánico/genética , Polimorfismo Genético , Genotipo , Frecuencia de los Genes/genética , Polimorfismo de Nucleótido Simple/genética
19.
J Control Release ; 361: 727-749, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37591461

RESUMEN

CRISPR/Cas9 genome editing is a promising therapeutic technique, which makes precise and rapid gene editing technology possible on account of its high sensitivity and efficiency. CRISPR/Cas9 system has been proved to able to effectively disrupt and modify genes, which shows great potential for cancer treatment. Current researches proves that virus vectors are capable of effectively delivering the CRISPR/Cas9 system, but immunogenicity and carcinogenicity caused by virus transmission still trigger serious consequences. Therefore, the greatest challenge of CRISPR/Cas9 for cancer therapy lies on how to deliver it to the target tumor site safely and effectively. Non-viral delivery systems with specific targeting, high loading capacity, and low immune toxicity are more suitable than viral vectors, which limited by uncontrollable side effects. Their medical advances and applications have been widely concerned. Herein, we present the molecule mechanism and different construction strategies of CRISPR/Cas9 system for editing genes at the beginning of this research. Subsequently, several common CRISPR/Cas9 non-viral deliveries for cancer treatment are introduced. Lastly, based on the main factors limiting the delivery efficiency of non-viral vectors proposed in the existing researches and literature, we summarize and discuss the main methods to solve these limitations in the existing tumor treatment system, aiming to introduce further optimization and innovation of the CRISPR/Cas9 non-viral delivery system suitable for cancer treatment.


Asunto(s)
Sistemas CRISPR-Cas , Neoplasias , Edición Génica , Tecnología , Neoplasias/genética , Neoplasias/terapia
20.
Psychol Res Behav Manag ; 16: 4353-4365, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37908679

RESUMEN

Objective: Learner dependence on short videos has many pitfalls for learning outcomes, but the negative effects of excessive short video use have been little discussed in the learning psychology literature. Therefore, this study investigated the effects of excessive short video use on anxiety, depression, prospective memory, and academically delayed gratification (ADOG) in relation to online gaming-related behaviours, and explored the possible mechanisms by which excessive online gaming and short video use may lead to decreased ADOG, to expand our understanding of excessive short video use. Methods: Based on the whole class random sampling method, a questionnaire survey was conducted among college students in Northern Anhui, China from May 7 to July 27, 2022. The questionnaires included the Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire Scale (PHQ-9), Prospective and Retrospective Memory (PRM) Questionnaire, and ADOG Scale. Results: A total of 1016 participants completed the survey. The study found that of all the internet behaviors, 20.8% of the college students mainly played online games, 43.9% mainly played short videos, and 35.3% conducted other online behaviors. When compared with other internet behaviors, online gaming and short video behaviors can cause more serious anxiety/depression and worse PRM and ADOG scores. As time spent playing online games and short videos increased, anxiety and depression became worse, and the scores for PRM and ADOG also declined. Anxiety, depression, and PRM mediate the relationship between time spent on online gaming/short videos and ADOG. Conclusion: Excessive short videos behaviour may produce the same psychological problems and learning problems as online gaming disorder. Excessive short video and online gaming behaviors may affect ADOG performance through anxiety, depression, and prospective memory. These findings could be used as a basis for future studies on the improvement of ADOG.

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