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1.
Chem Commun (Camb) ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38747147

RESUMEN

Here, we describe an iron-catalyzed benzylic C-H thiolation of alkylarenes via photoinduced ligand-to-metal charge-transfer. The protocol features operational simplicity, mild reaction conditions, and the use of FeCl3 as catalyst and thiols/disulfides as sulfur sources, which enables the transformation of diverse benzylic C-H bonds into C-S bonds with a high efficiency.

2.
Sci Rep ; 14(1): 7666, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561384

RESUMEN

Hepatocellular carcinoma (HCC) is a malignancy with poor prognosis. Abnormal expression of H3-H4 histone chaperones has been identified in many cancers and holds promise as a biomarker for diagnosis and prognosis. However, systemic analysis of H3-H4 histone chaperones in HCC is still lacking. Here, we investigated the expression of 19 known H3-H4 histone chaperones in HCC. Integrated analysis of multiple public databases indicated that these chaperones are highly expressed in HCC tumor tissues, which was further verified by immunohistochemistry (IHC) staining in offline samples. Additionally, survival analysis suggested that HCC patients with upregulated H3-H4 histone chaperones have poor prognosis. Using LASSO and Cox regression, we constructed a two-gene model (ASF1A, HJURP) that accurately predicts prognosis in ICGC-LIRI and GEO HCC data, which was further validated in HCC tissue microarrays with follow-up information. GSEA revealed that HCCs in the high-risk group were associated with enhanced cell cycle progression and DNA replication. Intriguingly, HCCs in the high-risk group exhibited increased immune infiltration and sensitivity to immune checkpoint therapy (ICT). In summary, H3-H4 histone chaperones play a critical role in HCC progression, and the two-gene (ASF1A, HJURP) risk model is effective for predicting survival outcomes and sensitivity to immunotherapy for HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Chaperonas de Histonas/metabolismo , Histonas/genética , Histonas/metabolismo , Neoplasias Hepáticas/genética , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Pronóstico
3.
J Glob Antimicrob Resist ; 37: 179-184, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38561142

RESUMEN

OBJECTIVES: This study aimed to isolate a phage capable of lysing carbapenem-resistant Klebsiella pneumoniae (CRKP) and to analyse its biological characteristics and whole-genome sequence. METHODS: The phage was isolated and purified from the sewage. Transmission electron microscopy (TEM) was employed to observe the bacteriophage's morphology. Phenotypic characterization of the bacteriophages was determined. The genomic information was analysed. Evolutionary relationships were established through comparative genomics, proteomics, and phylogenetic analysis. RESULTS: The isolation of a virulent phage, named Klebsiella phage vB_KpnM_KpVB3, was notable for forming 6-7 mm transparent circular zones, each surrounded by a distinct halo. The phage had a head diameter of ca. 30 nm and a tail length of ca. 20 nm, being identified as a member of the Myoviridae family and the Caudovirales order. The optimal multiplicity of infection (MOI) was 0.00001, with an incubation period of 20 minutes and a lysis period of 60 minutes, and the number of released phages after lysis was 133±35 PFU/cell. The phage was relatively stable at temperatures ranging from 10°C to 40°C and at pH values ranging from 3 to 11. Its lytic efficiency against CRKP was 30.30%. It has been shown to be able to destroy the biofilm of host bacteria. The bacteriophage genome consists of double-stranded DNA (dsDNA) with a total length of 48,394 base pairs, a GC content of 48.99%, and 78 open reading frames (ORFs). CONCLUSION: The study resulted in the isolation vB_KpnM_KpVB3, a phage demonstrating potential therapeutic efficacy against infections caused by CRKP.

4.
Biomolecules ; 14(4)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38672486

RESUMEN

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif is found next to another ill-defined cysteine that we show is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCMs) suggests a candidate Fe-S cluster ligand role. Hence, we generated, by site-directed DPH1 and DPH2 mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo.


Asunto(s)
Secuencias de Aminoácidos , Cisteína , Histidina/análogos & derivados , Proteínas Represoras , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Cisteína/metabolismo , Cisteína/genética , Cisteína/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimología , Multimerización de Proteína , Liasas de Carbono-Azufre/metabolismo , Liasas de Carbono-Azufre/química , Liasas de Carbono-Azufre/genética , Mutagénesis Sitio-Dirigida
5.
Heliyon ; 10(5): e27322, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38463802

RESUMEN

Sorafenib resistance is one of the main causes of poor prognosis in patients with advanced hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) function as suppressors or oncogenic factors during tumor progression and drug resistance. Here, to identify therapeutic targets for HCC, the biological mechanisms of abnormally expressed lncRNAs were examined in sorafenib-resistant HCC cells. Specifically, we established sorafenib-resistant HCC cell lines (Huh7-S and SMMC7721-S), which displayed an epithelial-mesenchymal transition (EMT) phenotype. Transcriptome sequencing (RNA-Seq) was performed to established differential lncRNA expression profiles for sorafenib-resistant cells. Through this analysis, we identified LINC00540 as significantly up-regulated in sorafenib-resistant cells and a candidate lncRNA for further mechanistic investigation. Functionally, LINC00540 knockdown promoted sorafenib sensitivity and suppressed migration, invasion, EMT and the activation of PI3K/AKT signaling pathway in sorafenib-resistant HCC cells, whereas overexpression of LINC00540 resulted in the opposite effects in parental cells. LINC00540 functions as a competing endogenous RNA (ceRNA) by competitively binding to miR-4677-3p , thereby promoting AKR1C2 expression. This is the first study that demonstrates a role for LINC00540 in enhancing sorafenib resistance, migration and invasion of HCC cells through the LINC00540/miR-4677-3p/AKR1C2 axis, suggesting that LINC00540 may represent a potential therapeutic target and prognosis biomarker for HCC.

6.
Mol Carcinog ; 63(5): 991-1008, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38376345

RESUMEN

The worldwide incidence and mortality rates of esophageal squamous cell carcinoma (ESCC) have increased over the last decade. Moreover, molecular targets that may benefit the therapeutics of patients with ESCC have not been fully characterized. Our study discovered that thousand and one amino-acid protein kinase 1 (TAOK1) is highly expressed in ESCC tumor tissues and cell lines. Knock-down of TAOK1 suppresses ESCC cell proliferation in vitro and patient-derived xenograft or cell-derived xenograft tumors growth in vivo. Moreover, TAOK1 overexpression promotes ESCC growth in vitro and in vivo. Additionally, we identified that the natural small molecular compound resveratrol binds to TAOK1 directly and diminishes the kinase activity of TAOK1. Targeting TAOK1 directly with resveratrol significantly inhibits cell proliferation, induces cell cycle arrest and apoptosis, and suppresses tumor growth in ESCC. Furthermore, the silencing of TAOK1 or the application of resveratrol attenuated the activation of TAOK1 downstream signaling effectors. Interestingly, combining resveratrol with paclitaxel, cisplatin, or 5-fluorouracil synergistically enhanced their therapeutic effects against ESCC. In conclusion, this work illustrates the underlying oncogenic function of TAOK1 and provides a theoretical basis for the application of targeting TAOK1 therapy to the clinical treatment of ESCC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Proteínas Serina-Treonina Quinasas , Humanos , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Resveratrol/farmacología , Resveratrol/uso terapéutico
7.
Bioresour Technol ; 395: 130365, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38266784

RESUMEN

Regulatory complexities in lipogenesis hinder the harmonization of metabolic carbon precursors towards lipid synthesis. Exploring regulatory complexities in lipogenesis, this study identifies NADP+-dependent isocitrate dehydrogenase (IDH) in Tetradesmus obliquus as a key factor. Overexpression IDH in strains ToIDH-1 and ToIDH-2 resulted in a 1.69 and 1.64-fold increase in neutral lipids, respectively, compared to the wild type, with lipid yield reaching 234.56 and 227.17 mg/L. Notably, despite slower growth, the cellular biomass augmented to 790.67 mg/L. Metabolite analysis indicated a shift in carbon precursors from protein to lipid and carbohydrate synthesis. Morphological observations revealed increases in the volume and number of lipid droplets, alongside a change in the fatty acid profile favoring monounsaturated and saturated fatty acids. Furthermore, IDH overexpression enhanced NADPH production and antioxidant activity, thereby further boosting lipid accumulation when combined with salt stress. This study suggests a pathway for improved lipogenesis and algal growth via metabolic engineering.


Asunto(s)
Antioxidantes , Isocitrato Deshidrogenasa , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , NADP/metabolismo , NADPH Deshidrogenasa , Ácidos Grasos , Carbono
8.
Biomed Pharmacother ; 170: 115954, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38039753

RESUMEN

The potential of Ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia (FVIO-MHT) in solid tumor therapy has been demonstrated. However, the impact of FVIO-MHT on the tumor microenvironment (TME) remains unclear. This study utilized single-cell transcriptome sequencing to examine the alterations in the TME in response to FVIO-MHT in breast cancer. The results revealed the cellular composition within the tumor microenvironment (TME) was primarily modified due to a decrease in tumor cells and an increased infiltration of myeloid cells. Subsequently, an enhancement in active oxygen (ROS) metabolism was observed, indicating oxidative damage to tumor cells. Interestingly, FVIO-MHT reprogrammed the macrophages' phenotypes, as evidenced by alterations in the transcriptome characteristics associated with both classic and alternative activated phenotypes. And an elevated level of ROS generation and oxidative phosphorylation suggested that activated phagocytosis and inflammation occurred in macrophages. Additionally, cell-cell communication analysis revealed that FVIO-MHT attenuated the suppression between tumor cells and macrophages by inhibiting phagocytic checkpoint and macrophage migration inhibitory factor signaling pathways. Inhibition of B2m, an anti-phagocytosis checkpoint, could promote macrophage-mediated phagocytosis and significantly inhibit tumor growth. These data emphasize FVIO-MHT may promote the antitumor capabilities of macrophages by alleviating the suppression between tumor cells and macrophages.


Asunto(s)
Neoplasias de la Mama , Hipertermia Inducida , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Especies Reactivas de Oxígeno/farmacología , Macrófagos , Fenómenos Magnéticos , Perfilación de la Expresión Génica , Microambiente Tumoral
9.
Bioorg Med Chem Lett ; 94: 129462, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37652098

RESUMEN

Recently, PI3K and HDAC have been considered as promising targets for the cancer therapy. A couple of pan-PI3K/HDAC dual inhibitors have been developed as a new class of anticancer agents. Herein, we discovered a new series of (S)-N1-(thiazol-2-yl) pyrrolidine-1,2-dicarboxamide derivatives targeting PI3Kα/HDAC6. All the derivatives exerted dual-target inhibitory activities. Particularly, in the enzymatic selectivity assay, compound 21j was identified as a subtype-selective PI3Kα/HDAC6 dual inhibitor (IC50 = 2.9 and 26 nM against PI3Kα and HDAC6, respectively), which displayed high potency against L-363 cell line with IC50 value of 0.17 µM. In addition, 21j significantly inhibited phosphorylation of pAkt(Ser473) and induced accumulation of acetylated α-tubulin while having a negligible effect on the levels of acetylated Histone H3 and H4 at nanomolar level. Attributed to its favorable in vitro performance, 21j has the potential to alleviate the adverse effects resulted from pan-PI3K inhibition and pan-HDAC inhibition. It is valuable for further functional investigation as an anti-cancer agent.


Asunto(s)
Neoplasias , Humanos , Pruebas de Enzimas , Histona Desacetilasa 6 , Inhibidores de Histona Desacetilasas/farmacología , Histonas , Neoplasias/tratamiento farmacológico , Pirrolidinas , Fosfatidilinositol 3-Quinasa , Inhibidores de las Quinasa Fosfoinosítidos-3/química , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología
10.
Nanoscale Adv ; 5(14): 3629-3633, 2023 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-37441256

RESUMEN

Herein, we have designed and synthesized a novel type-I photosensitizer (PhPA) via Rh-catalyzed oxidative cyclization of diacetoxyterephthalamide with alkynes. The photoelectric properties, photosensitivity and photodegradation process of PhPA have been systematically investigated. The remarkable fluorescence quenching effect (ΦPL < 0.01) of PhPA suggests that the intersystem crossing from the singlet excited state to the reactive triplet state is enhanced by the enlarged conjugated backbone. Additionally, the ability of superoxide radical (O2-˙) generation was confirmed by electron paramagnetic resonance spectroscopy. Finally, the mechanism of PhPA photo-oxidative degradation via the structure of two metabolites is proposed.

11.
Molecules ; 28(9)2023 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-37175352

RESUMEN

Cationic polymeric materials and cell-penetrating peptides (CPPs) were often used as the delivery vectors in the evaluation of nucleic acid therapeutics. 10-23 DNAzyme is a kind of potential antisense therapeutics by catalytic cleavage of the disease-related RNAs. Here, lipofectamine 2000 and Tat peptide were evaluated for their effect on the catalytic activity of 10-23 DNAzyme, with the observed rate constant, thermal stability, CD spectra, and PAGE analysis, with a duplex DNA mimicking DNAzyme-substrate as a control. It was shown that the cationic carriers had a negative effect on the catalytic performance of the 10-23 DNAzyme. Significantly, the destabilizing effect of the cationic carriers on the duplex formation was noteworthy, as a duplex formation is an essential prerequisite in the silencing mechanisms of antisense and RNAi.


Asunto(s)
Péptidos de Penetración Celular , ADN Catalítico , ADN Catalítico/química , Péptidos de Penetración Celular/farmacología , Péptidos de Penetración Celular/química , Lípidos , ADN , Cationes
12.
Int J Mol Sci ; 24(5)2023 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-36901839

RESUMEN

NK-4 plays a key role in the treatment of various diseases, such as in hay fever to expect anti-allergic effects, in bacterial infections and gum abscesses to expect anti-inflammatory effects, in scratches, cuts, and mouth sores from bites inside the mouth for enhanced wound healing, in herpes simplex virus (HSV)-1 infections for antiviral effects, and in peripheral nerve disease that causes tingling pain and numbness in hands and feet, while NK-4 is used also to expect antioxidative and neuroprotective effects. We review all therapeutic directions for the cyanine dye NK-4, as well as the pharmacological mechanism of NK-4 in animal models of related diseases. Currently, NK-4, which is sold as an over-the-counter drug in drugstores, is approved for treating allergic diseases, loss of appetite, sleepiness, anemia, peripheral neuropathy, acute suppurative diseases, wounds, heat injuries, frostbite, and tinea pedis in Japan. The therapeutic effects of NK-4's antioxidative and neuroprotective properties in animal models are now under development, and we hope to apply these pharmacological effects of NK-4 to the treatment of more diseases. All experimental data suggest that different kinds of utility of NK-4 in the treatment of diseases can be developed based on the various pharmacological properties of NK-4. It is expected that NK-4 could be developed in more therapeutic strategies to treat many types of diseases, such as neurodegenerative and retinal degenerative diseases.


Asunto(s)
Herpes Simple , Infecciones por Herpesviridae , Animales , Células Asesinas Naturales , Carbocianinas
13.
Colloids Surf B Biointerfaces ; 225: 113253, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36934611

RESUMEN

Disulfiram (DSF), a drug for alcohol withdrawal, has attracted extensive scientific attention due to its potential to treat cancer. The metabolite of DSF, diethyl dithiocarbamate (DDTC), forms a Cu-DDTC complex in vivo with copper ions, which has been shown to be a proteasome inhibitor with high antitumor activity. However, the in vivo stability of Cu-DDTC complexes remains a challenge. In this study, the nanomedicine Cu-BTC@DDTC with high antitumor activity was prepared by using the nanoscale metal-organic framework (MOF) Cu-BTC as a carrier and loading diethyldithiocarbamate (DDTC) through coordination interaction. The results showed that Cu-BTC@DDTC had high drug loading and adequate stability, and exhibited DDTC-Cu(I) chemical valence characteristics and polycrystalline structure features. In vitro cytocompatibility investigation and animal xenograft tumor model evaluation demonstrated the anti-cancer potential of Cu-BTC@DDTC, especially the combination of Cu-BTC@DDTC with low-dose cisplatin showed significant antitumor effect and biosafety. This study provides a feasible protocol for developing antitumor drugs based on the drug repurposing strategy.


Asunto(s)
Alcoholismo , Ferroptosis , Melanoma , Estructuras Metalorgánicas , Síndrome de Abstinencia a Sustancias , Animales , Humanos , Ditiocarba/farmacología , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/metabolismo , Disulfiram/farmacología , Disulfiram/metabolismo , Melanoma/tratamiento farmacológico , Cobre/química , Línea Celular Tumoral , Sistema de Transporte de Aminoácidos y+
14.
Proc Natl Acad Sci U S A ; 120(1): e2211927120, 2023 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-36574698

RESUMEN

The limited efficacy of the current antitumor microenvironment strategies is due in part to the poor understanding of the roles and relative contributions of the various tumor stromal cells to tumor development. Here, we describe a versatile in vivo anthrax toxin protein delivery system allowing for the unambiguous genetic evaluation of individual tumor stromal elements in cancer. Our reengineered tumor-selective anthrax toxin exhibits potent antiproliferative activity by disrupting ERK signaling in sensitive cells. Since this activity requires the surface expression of the capillary morphogenesis protein-2 (CMG2) toxin receptor, genetic manipulation of CMG2 expression using our cell-type-specific CMG2 transgenic mice allows us to specifically define the role of individual tumor stromal cell types in tumor development. Here, we established mice with CMG2 only expressed in tumor endothelial cells (ECs) and determined the specific contribution of tumor stromal ECs to the toxin's antitumor activity. Our results demonstrate that disruption of ERK signaling only within tumor ECs is sufficient to halt tumor growth. We discovered that c-Myc is a downstream effector of ERK signaling and that the MEK-ERK-c-Myc central metabolic axis in tumor ECs is essential for tumor progression. As such, disruption of ERK-c-Myc signaling in host-derived tumor ECs by our tumor-selective anthrax toxins explains their high efficacy in solid tumor therapy.


Asunto(s)
Células Endoteliales , Neoplasias , Ratones , Animales , Células Endoteliales/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Receptores de Péptidos/genética , Receptores de Péptidos/metabolismo , Transducción de Señal , Antígenos Bacterianos/metabolismo , Neoplasias/genética , Microambiente Tumoral
15.
Org Lett ; 24(41): 7637-7642, 2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36218287

RESUMEN

Herein, we report a method that uses antifungal tavaborole as a co-catalyst for direct α-C-H alkylation of structurally diverse alcohols through photoredox catalysis. The protocol features mild conditions, remarkable scope, and wide functional group tolerance, which allows for the construction of a wide array of highly functionalized alcohols, including homoserine derivatives and C-glycosyl amino acids. We also demonstrate the synthetic applications of this methodology to the late-stage functionalization of pharmaceuticals and natural products.


Asunto(s)
Alcoholes , Productos Biológicos , Alcoholes/química , Homoserina , Antifúngicos , Oxidación-Reducción , Catálisis , Alquilación , Aminoácidos/química , Preparaciones Farmacéuticas
16.
Eur J Pediatr ; 181(12): 4019-4037, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36109390

RESUMEN

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.


Asunto(s)
Antipiréticos , COVID-19 , Insuficiencia Respiratoria , Adolescente , Niño , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Inmunoglobulinas Intravenosas , Oxígeno
17.
Pharmacogenomics ; 23(15): 835-845, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36169168

RESUMEN

Objective: To develop an accurate and rapid real-time PCR technique for HLA-B*15:02 genotyping and investigate HLA-B*15:02 allele frequency in four ethnic populations in China. Materials & methods: Based on the highly specific representative markers, a real-time PCR assay was developed for HLA-B*15:02 genotyping, and HLA-B*15:02 allele frequencies were screened in four ethnic populations of China. Sequence-based typing was used to validate the accuracy of the assay. Results: The sensitivity and specificity of the assay were 100%, and the detection limit was 0.2 ng. The frequency of HLA-B*15:02 alleles distributed in the Bouyei population was significantly higher than in the Han group (p < 0.01). Neither the Tibetan nor the Uyghur population carried the HLA-B*15:02 haplotype. Conclusion: The authors developed an accurate HLA-B*15:02 genotyping method for evaluating the risk of adverse drug reactions induced by carbamazepine in various ethnic populations in China.


Asunto(s)
Pueblo Asiatico , Antígenos HLA-B , Humanos , Genotipo , Antígenos HLA-B/genética , Frecuencia de los Genes/genética , Pueblo Asiatico/genética , Alelos , Carbamazepina , China
18.
Fitoterapia ; 162: 105290, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36064152

RESUMEN

Excess levels of chemical hepatotoxicants (alcohol, aflatoxin B1), oxidative drugs (acetaminophen) and some cytokines (ET-1, TGF-ß1) can induce chronic or acute liver injury. After these, the severe hepatic disease, especially the liver fibrosis (LF) occurs without taking measures, which brings threat to human health. The dibenzocyclooctadiene lignans of S. chinensis (SCDLs) were found to act as the hepatoprotective components via blocking endothelin B receptor (ETBR). While study on its anti-LF mechanisms especially for its refined compound of schisantherin D (SC-D) is still a lack. So this study aims to investigate the anti-fibrosis effect of SC-D with in vitro and in vivo assays. Bioinformatics analysis revealed the close relations of ETBR to Smad2, Smad3, Nrf2, etc. in LF-related signaling pathways (such as TGF-ß/Smad and Nrf2/ARE). Histopathological staining on livers showed the recovery trend in SC-D treated LF mice. SC-D also modulated expressions of ETBR and fibrosis or anti-oxidative related proteins (such as TIMP1, p-Smad2/3, Nrf2, Smad7, etc.) in LF mice livers. Serum levels of TNF-α, COLI, ALT, AST and LDH in SC-D treated mice were also downregulated compared with LF mice, and upregulated expression of GSH. In vitro studies, SC-D also modulated expressions of LF-related proteins to the normal tendency in LX-2 cell, while weakened its anti- LX-2 proliferation effect by transfections of si-Smad7 or si-Nrf2. Accordingly the anti-LF approach of SC-D showed relations with modulating ETBR linked fibrosis and anti-oxidative related signaling. Also, Smad7 and Nrf2 might be the key factors for SC-D mediated anti-LF effect.


Asunto(s)
Lignanos , Schisandra , Acetaminofén , Aflatoxina B1 , Animales , Dioxoles , Humanos , Lignanos/farmacología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Ratones , Estructura Molecular , Factor 2 Relacionado con NF-E2/metabolismo , Receptor de Endotelina B/uso terapéutico , Schisandra/química , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1 , Factor de Necrosis Tumoral alfa
19.
Eur. j. pediatr ; 181(2): 4019-4037, 20220916.
Artículo en Inglés | BIGG - guías GRADE | ID: biblio-1412428

RESUMEN

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. Conclusion: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged.


Asunto(s)
Humanos , Niño , Adolescente , Vacunas contra la COVID-19 , SARS-CoV-2/inmunología , COVID-19/inmunología
20.
Comput Intell Neurosci ; 2022: 2286803, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35898780

RESUMEN

Exploratory spatial data analysis (ESDA) shows that there is a significant spatial autocorrelation of tourism development in China, which is manifested by the aggregation of spatial distribution. The results of the great likelihood estimation of the spatial lag model show that the parameters ρ of both the total tourism income model and the domestic income model are significantly positive, indicating that the spatial linkage between agricultural and rural tourism income is very strong and the spillover effect of agricultural and rural tourism is larger than that of overall tourism. Tourism superstructure facilities, human resources, and tourism infrastructure are statistically significant and are important influencing factors for overall tourism and agricultural and rural tourism development. And the overall fit of agricultural and rural tourism model is poor. The findings of the study better grasp how to make rural tourism make a greater contribution to the regional economy of Chengdu and maximize its positive role, and put forward relevant countermeasure suggestions, which will provide theoretical guidance and decision-making reference for relevant departments on how to better play the economic effect of tourism, and will also have a realistic reference role on how to develop rural tourism in western cities of China.


Asunto(s)
Análisis de Datos , Turismo , Agricultura , China , Humanos , Actividades Recreativas , Análisis Espacial
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