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1.
Plant J ; 115(1): 205-219, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36999610

RESUMEN

Low temperature and abscisic acid (ABA) are the two main factors that induce anthocyanin synthesis; however, their potential relationships in governing anthocyanin biosynthesis in Solanum lycopersicum (tomato) seedlings remains unclear. Our study revealed the involvement of the transcription factor SlAREB1 in the low-temperature response of tomato seedlings via the ABA-dependent pathway, for a specific temperature range. The overexpression of SlAREB1 enhanced the expression of anthocyanin-related genes and the accumulation of anthocyanins, especially under low-temperature conditions, whereas silencing SlAREB1 dramatically reduced gene expression and anthocyanin accumulation. There is a direct interaction between SlAREB1 and the promoters of SlDFR and SlF3'5'H, which are structural genes that impact anthocyanin biosynthesis. SlAREB1 can regulate anthocyanins through controlling SlDFR and SlF3'5'H expression. Accordingly, SlAREB1 takes charge of regulating anthocyanin biosynthesis in tomato seedlings via the ABA-dependent pathway at low temperatures.


Asunto(s)
Solanum lycopersicum , Solanum lycopersicum/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Antocianinas , Temperatura , Ácido Abscísico/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
2.
Cancer Immunol Immunother ; 72(2): 351-369, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35895109

RESUMEN

BACKGROUND: Immunotherapy is an emerging cancer therapy with potential great success; however, immune checkpoint inhibitor (e.g., anti-PD-1) has response rates of only 10-30% in solid tumor because of the immunosuppressive tumor microenvironment (TME). This affliction can be solved by vascular normalization and TME reprogramming. METHODS: By using the single-cell RNA sequencing (scRNAseq) approach, we tried to find out the reprogramming mechanism that the Fc-VEGF chimeric antibody drug (Fc-VFD) enhances immune cell infiltration in the TME. RESULTS: In this work, we showed that Fc-VEGF121-VEGF165 (Fc-VEGF chimeric antibody drug, Fc-VFD) arrests excess angiogenesis and tumor growth through vascular normalization using in vitro and in vivo studies. The results confirmed that the treatment of Fc-VFD increases immune cell infiltration including cytotoxic T, NK, and M1-macrophages cells. Indeed, Fc-VFD inhibits Lon-induced M2 macrophages polarization that induces angiogenesis. Furthermore, Fc-VFD inhibits the secretion of VEGF-A, IL-6, TGF-ß, or IL-10 from endothelial, cancer cells, and M2 macrophage, which reprograms immunosuppressive TME. Importantly, Fc-VFD enhances the synergistic effect on the combination immunotherapy with anti-PD-L1 in vivo. CONCLUSIONS: In short, Fc-VFD fusion normalizes intratumor vasculature to reprogram the immunosuppressive TME and enhance cancer immunotherapy.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Microambiente Tumoral , Factor A de Crecimiento Endotelial Vascular , Inmunoterapia , Antineoplásicos/farmacología , Inmunosupresores/farmacología
3.
J Virol ; 96(6): e0214121, 2022 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-35044216

RESUMEN

Due to the high mutation rate of influenza virus and the rapid increase of drug resistance, it is imperative to discover host-targeting antiviral agents with broad-spectrum antiviral activity. Considering the discrepancy between the urgent demand of antiviral drugs during an influenza pandemic and the long-term process of drug discovery and development, it is feasible to explore host-based antiviral agents and strategies from antiviral drugs on the market. In the current study, the antiviral mechanism of arbidol (ARB), a broad-spectrum antiviral drug with potent activity at early stages of viral replication, was investigated from the aspect of hemagglutinin (HA) receptors of host cells. N-glycans that act as the potential binding receptors of HA on 16-human bronchial epithelial (16-HBE) cells were comprehensively profiled for the first time by using an in-depth glycomic approach based on TiO2-PGC chip-Q-TOF MS. Their relative levels upon the treatment of ARB and virus were carefully examined by employing an ultra-high sensitive qualitative method based on Chip LC-QQQ MS, showing that ARB treatment led to significant and extensive decrease of sialic acid (SA)-linked N-glycans (SA receptors), and thereby impaired the virus utilization on SA receptors for rolling and entry. The SA-decreasing effect of ARB was demonstrated to result from its inhibitory effect on sialyltransferases (ST), ST3GAL4 and ST6GAL1 of 16-HBE cells. Silence of STs, natural ST inhibitors, as well as sialidase treatment of 16-HBE cells, resulted in similar potent antiviral activity, whereas ST-inducing agent led to the diminished antiviral effect of ARB. These observations collectively suggesting the involvement of ST inhibition in the antiviral effect of ARB. IMPORTANCE This study revealed, for the first time, that ST inhibition and the resulted destruction of SA receptors of host cells may be an underlying mechanism for the antiviral activity of ARB. ST inhibition has been proposed as a novel host-targeting antiviral approach recently and several compounds are currently under exploration. ARB is the first antiviral drug on the market that was found to possess ST inhibiting function. This will provide crucial evidence for the clinical usages of ARB, such as in combination with neuraminidase (NA) inhibitors to exert optimized antiviral effect, etc. More importantly, as an agent that can inhibit the expression of STs, ARB can serve as a novel lead compound for the discovery and development of host-targeting antiviral drugs.


Asunto(s)
Indoles , Sialiltransferasas , Sulfuros , Antivirales/farmacología , Antivirales/uso terapéutico , Línea Celular , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Células Epiteliales , Glicómica , Hemaglutininas , Humanos , Indoles/farmacología , Indoles/uso terapéutico , Neuraminidasa/farmacología , Polisacáridos/metabolismo , Sialiltransferasas/antagonistas & inhibidores , Sulfuros/farmacología , Sulfuros/uso terapéutico
4.
PLoS Pathog ; 17(8): e1009758, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34379705

RESUMEN

Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.


Asunto(s)
COVID-19 , Enfermedades Transmisibles Emergentes , Modelos Animales de Enfermedad , Células 3T3 , Enzima Convertidora de Angiotensina 2/genética , Animales , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/uso terapéutico , COVID-19/inmunología , COVID-19/patología , COVID-19/fisiopatología , Chlorocebus aethiops , Dependovirus/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Transducción Genética , Células Vero
5.
Appl Microbiol Biotechnol ; 107(23): 7197-7211, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37741939

RESUMEN

Tetanus toxin (TeNT) and botulinum neurotoxins (BoNTs) are neuroprotein toxins, with the latter being the most toxic known protein. They are structurally similar and contain three functional domains: an N-terminal catalytic domain (light chain), an internal heavy-chain translocation domain (HN domain), and a C-terminal heavy chain receptor binding domain (Hc domain or RBD). In this study, fusion functional domain molecules consisting of the TeNT RBD (THc) and the BoNT/A RBD (AHc) (i.e., THc-Linker-AHc and AHc-Linker-THc) were designed, prepared, and identified. The interaction of each Hc domain and the ganglioside receptor (GT1b) or the receptor synaptic vesicle glycoprotein 2 (SV2) was explored in vitro. Their immune response characteristics and protective efficacy were investigated in animal models. The recombinant THc-linker-AHc and AHc-linker-THc proteins with the binding activity had the correct size and structure, thus representing novel subunit vaccines. THc-linker-AHc and AHc-linker-THc induced high levels of specific neutralizing antibodies, and showed strong immune protective efficacy against both toxins. The high antibody titers against the two novel fusion domain molecules and against individual THc and AHc suggested that the THc and AHc domains, as antigens in the fusion functional domain molecules, do not interact with each other and retain their full key epitopes responsible for inducing neutralizing antibodies. Thus, the recombinant THc-linker-AHc and AHc-linker-THc molecules are strong and effective bivalent biotoxin vaccines, protecting against two biotoxins simultaneously. Our experimental design will be valuable to develop recombinant double-RBD fusion molecules as potent bivalent subunit vaccines against bio-toxins. KEY POINTS: • Double-RBD fusion molecules from two toxins had the correct structure and activity. • THc-linker-AHc and AHc-linker-THc efficiently protected against both biotoxins. • Such bivalent biotoxin vaccines based on the RBD are a valuable experimental design.


Asunto(s)
Toxinas Botulínicas Tipo A , Toxina Tetánica , Animales , Toxina Tetánica/genética , Toxina Tetánica/metabolismo , Toxinas Botulínicas Tipo A/genética , Toxinas Botulínicas Tipo A/metabolismo , Unión Proteica , Anticuerpos Neutralizantes , Vacunas de Subunidad/genética
6.
Nucleic Acids Res ; 49(1): 38-52, 2021 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-33290562

RESUMEN

Acquired drug resistance is a major obstacle in cancer therapy. Recent studies revealed that reprogramming of tRNA modifications modulates cancer survival in response to chemotherapy. However, dynamic changes in tRNA modification were not elucidated. In this study, comparative analysis of the human cancer cell lines and their taxol resistant strains based on tRNA mapping was performed by using UHPLC-MS/MS. It was observed for the first time in all three cell lines that 4-demethylwyosine (imG-14) substitutes for hydroxywybutosine (OHyW) due to tRNA-wybutosine synthesizing enzyme-2 (TYW2) downregulation and becomes the predominant modification at the 37th position of tRNAphe in the taxol-resistant strains. Further analysis indicated that the increase in imG-14 levels is caused by downregulation of TYW2. The time courses of the increase in imG-14 and downregulation of TYW2 are consistent with each other as well as consistent with the time course of the development of taxol-resistance. Knockdown of TYW2 in HeLa cells caused both an accumulation of imG-14 and reduction in taxol potency. Taken together, low expression of TYW2 enzyme promotes the cancer survival and resistance to taxol therapy, implying a novel mechanism for taxol resistance. Reduction of imG-14 deposition offers an underlying rationale to overcome taxol resistance in cancer chemotherapy.


Asunto(s)
Resistencia a Antineoplásicos/genética , Paclitaxel/farmacología , Procesamiento Postranscripcional del ARN/genética , ARN Neoplásico/química , ARN de Transferencia de Fenilalanina/química , Células A549 , Secuencia de Bases , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Regulación hacia Abajo , Resistencia a Antineoplásicos/fisiología , Femenino , Regulación Enzimológica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Guanosina/análogos & derivados , Guanosina/química , Guanosina/metabolismo , Células HeLa , Humanos , Estructura Molecular , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Conformación de Ácido Nucleico , Neoplasias Ováricas/patología , ARN Neoplásico/fisiología , ARN de Transferencia de Fenilalanina/fisiología , Espectrometría de Masas en Tándem , Ensayo de Tumor de Célula Madre
7.
BMC Palliat Care ; 22(1): 49, 2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37098562

RESUMEN

BACKGROUND: Hospice and palliative care nursing (HPCN) in China is mainly available at public primary care institutions, where nursing homes (NHs) are rarely involved. Nursing assistants (NAs) play an essential role in HPCN multidisciplinary teams, but little is known about their attitudes towards HPCN and related factors. METHODS: A cross-sectional study was designed to evaluate NAs' attitudes towards HPCN with an indigenised scale in Shanghai. A total of 165 formal NAs were recruited from 3 urban and 2 suburban NHs between October 2021 and January 2022. The questionnaire was composed of four parts: demographic characteristics, attitudes (20 items with four sub-concepts), knowledge (nine items), and training needs (nine items). Descriptive statistics, independent samples t-test, one-way ANOVA, Pearson's correlation, and multiple linear regression were performed to analyse NAs' attitudes, influencing factors, and their correlations. RESULTS: A total of 156 questionnaires were valid. The mean score of attitudes was 72.44 ± 9.56 (range:55-99), with a mean item score of 3.6 ± 0.5 (range:1-5). The highest score rate was "perception of the benefits for the life quality promotion" (81.23%), and the lowest score rate was "perception of the threats from the worsening conditions of advanced patients" (59.92%). NAs' attitudes towards HPCN were positively correlated with their knowledge score (r = 0.46, P < 0.01) and training needs (r = 0.33, P < 0.01). Marital status (ß = 0.185), previous training experience (ß = 0.201), location of NHs (ß = 0.193), knowledge (ß = 0.294), and training needs (ß = 0.157) for HPCN constituted significant predictors of attitudes (P < 0.05), which explained 30.8% of the overall variance. CONCLUSION: NAs' attitudes towards HPCN were moderate, but their knowledge should be improved. Targeted training is highly recommended to improve the participation of positive and enabled NAs and to promote high-quality universal coverage of HPCN in NHs.


Asunto(s)
Actitud del Personal de Salud , Enfermería de Cuidados Paliativos al Final de la Vida , Asistentes de Enfermería , Humanos , China , Estudios Transversales , Pueblos del Este de Asia , Conocimientos, Actitudes y Práctica en Salud , Asistentes de Enfermería/educación , Casas de Salud , Cuidados Paliativos , Encuestas y Cuestionarios
8.
J Prosthet Dent ; 130(3): 288-294, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34887077

RESUMEN

This technique report presents a novel method of digitally replicating a treatment denture and converting it into a definitive denture. The procedure accurately duplicates the appearance of the mucosal surface and border of the treatment dentures, mounts the jaw relation on a virtual articulator to arrange artificial teeth, and optimizes the occlusion based on recorded mandibular motion tracks. This technique uses personalized jaw relation transfer and dynamic occlusal adjustment to establish balanced occlusion, which accomplishes the digital duplication of the treatment denture with high accuracy and minimal effort.


Asunto(s)
Dentadura Completa , Ajuste Oclusal , Flujo de Trabajo , Diseño de Dentadura/métodos , Oclusión Dental , Articuladores Dentales , Registro de la Relación Maxilomandibular/métodos
9.
Palliat Support Care ; : 1-7, 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36912179

RESUMEN

OBJECTIVES: Given the rising burden of palliative care and the limited human resources for its facilitation in China, volunteers are becoming increasingly indispensable. In particular, there is a high demand for volunteers who can serve as spiritual caregivers. However, a volunteer's ability to provide good spiritual care in a palliative setting may be influenced by their attitude toward palliative care. To uncover the current state of spiritual caregiving in palliative settings in China and insights into best practices for its improvement, this study measured spiritual care competence and identified its influencing factors and explored its relationship with attitudes toward palliative care among volunteers. Notably, this study is the first to consider spiritual care competence alongside attitudes toward palliative care. METHODS: A descriptive cross-sectional study using online survey methods was conducted with 385 volunteers in Shanghai, China. Data were collected using a structured questionnaire. RESULTS: Volunteers demonstrated relatively low levels of spiritual care competence (58.50 ± 10.92). Statistically significant correlations were found between spiritual care competence and the following variables: age, educational background, marital status, religious beliefs, occupational status, and relevant training and practical experience. Attitude toward palliative care significantly correlated with spiritual care competence (r = 0.49, p < 0.001). SIGNIFICANCE OF RESULTS: To continually improve volunteers' spiritual care competence, diversified education and training programs about spiritual care should be designed for different kinds of volunteers; moreover, because attitude toward palliative care significantly impacted spiritual care competence, such programs should encourage positive attitudes toward palliative care.

10.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(5): 539-544, 2023 Sep 30.
Artículo en Zh | MEDLINE | ID: mdl-37753894

RESUMEN

The primary cause of injury and death in the elderly has been reflected in fall the elderly, so the application of reasonable and effective prevention strategies has great significance in reducing the risk of fall in the elderly. The research progress of virtual reality technology applied in preventing fall in the elderly at home and abroad over the years was systematically reviewed in this study. The mechanism of the technology in preventing fall in the elderly was mainly elaborated from five aspects of improving balance ability, gait disturbance, cognitive impairment, muscle strength and the fear psychology of falling. The purpose of this thesis is to broaden the research ideas of medical personnel on the prevention of fall of the elderly, provide more effective clinical practice plans, reduce the occurrence of fall, and guarantee the safety of the elderly.


Asunto(s)
Marcha , Realidad Virtual , Anciano , Humanos , Fuerza Muscular , Tecnología
11.
Med Sci Monit ; 28: e936963, 2022 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-35733327

RESUMEN

BACKGROUND A keloid is a pathological scar hyperplasia that is affected by genetic and environmental factors. Although the involvement of cytotoxic granzyme B in keloids has been recognized, there is almost no research on granzyme B (GZMB) gene polymorphisms and keloids. This study aimed to explore the relationship between genetic polymorphisms of GZMB and postsurgical keloid susceptibility in the Han Chinese population. MATERIAL AND METHODS A total of 3078 participants, including 990 patients with postsurgical keloids and 2088 controls without postsurgical keloids, were enrolled. We selected 15 common DNA variants in the GZMB gene for analysis. Associations were analyzed in both single marker-based and haplotype-based methods. The Genotype-Tissue Expression database was used to examine the biological significance of the targeted single nucleotide polymorphisms (SNPs). RESULTS SNP rs8192917 was found to be associated with the susceptibility of keloids (t statistic=4.82, P=1.47×10⁻6). An increased risk of keloids was significantly associated with the minor allele (C allele) of rs8192917 (odds ratio=1.33; 95% CI=1.18-1.49], P=1.47×10⁻6). In addition, a significant association was reported for genotypes of rs8192917 and clinical severity of keloids (χ²=10.61, P=0.03). CONCLUSIONS The results suggested there are significant associations between common genetic variants in GZMB and the susceptibility of postsurgical keloids in the Chinese Han population. These genetic polymorphisms were also related with the severity of postsurgical keloid symptoms in participants with keloids. The current study can contribute to future etiological and clinical research of keloids.


Asunto(s)
Granzimas , Queloide , Polimorfismo de Nucleótido Simple , Alelos , Estudios de Casos y Controles , China , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Granzimas/genética , Humanos , Queloide/genética , Complicaciones Posoperatorias
12.
Int J Mol Sci ; 23(5)2022 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35269804

RESUMEN

Although pituitary adenomas are histologically benign, they are often accompanied by multiple complications, such as cardiovascular disease and metabolic dysfunction. In the present study, we repositioned the Food and Drug Administration -approved immune regulator tamoxifen to target STAT6 based on the genomics analysis of PAs. Tamoxifen inhibited the proliferation of GH3 and AtT-20 cells with respective IC50 values of 9.15 and 7.52 µM and increased their apoptotic rates in a dose-dependent manner. At the molecular level, tamoxifen downregulated phosphorylated PI3K, phosphorylated AKT and the anti-apoptotic protein Bcl-2 and increased the expression of pro-apoptotic proteins p53 and Bax in GH3 and AtT-20 cells. Furthermore, tamoxifen also inhibited the migration of both cell lines by reprogramming tumor-associated macrophages to the M1 phenotype through STAT6 inactivation and inhibition of the macrophage-specific immune checkpoint SHP1/SHP. Finally, administration of tamoxifen (20, 50, 100 mg·kg-1·d-1, for 21 days) inhibited the growth of pituitary adenomas xenografts in nude mice in a dose-dependent manner. Taken together, tamoxifen is likely to be a promising combination therapy for pituitary adenomas and should be investigated further.


Asunto(s)
Adenoma , Neoplasias Hipofisarias , Adenoma/genética , Animales , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Humanos , Ratones , Ratones Desnudos , Neoplasias Hipofisarias/patología , Tamoxifeno/farmacología , Tamoxifeno/uso terapéutico
13.
Basic Res Cardiol ; 116(1): 53, 2021 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-34546460

RESUMEN

We recently identified oncologic miR-182 as a new regulator of pulmonary artery hypertension (PAH) that targets myeloid-associated differentiation marker (Myadm), which is expressed in bone marrow stem cells and multipotent progenitors. Both miR-182 and Myadm are expressed in the cardiopulmonary system and correlated with the balance between the bone morphogenetic protein (BMP) and the transforming growth factor (TGF)-ß signalling pathways, which are disturbed in PAH. We hypothesize that miR-182/Myadm are involved in BMP-TGF-ß-signalling way in PAH. Hypoxia triggered pathological progression in cardiopulmonary PAH in vivo and in vitro; these changes were accompanied by strongly dowregulated BMP/SMAD1/5/8 expression and enhanced TGF-ß/SMAD2/3 signalling pathway, favouring SMAD4/SMAD2 transcript formation and inhibiting the PAH negative regulator Id1 expression. miR-182 gain-of-function significantly inhibited the pathological progression in hypoxia-induced PAH (HPH) in vivo and in vitro, with a restoration of the balance in BMP-TGF-ß signalling pathway. This recovery was abrogated by overexpression of Myadm. Conversely, loss-of-function of miR-182 increased the pathological progression of HPH followed by severe disturbance of BMP and TGF-ß signal transduction and reduced Id1 expression, which was restored by Myadm knockdown. We also showed that the miR-182/Myadm relate BMP-TGF-ß pathway is associated with NOS3/NO/cGMP via the crosstalk between endothelial cells and smooth muscle cells. Our findings further support the therapeutic significance of miR-182/Myadm in PAH via the balance of BMP- and TGF-ß-associated mechanisms.


Asunto(s)
Hipertensión Pulmonar , MicroARNs , Proteínas Morfogenéticas Óseas , Células Endoteliales , Humanos , Hipertensión Pulmonar/genética , Hipoxia , MicroARNs/genética , Proteínas Proteolipídicas Asociadas a Mielina y Linfocito , Arteria Pulmonar , Factor de Crecimiento Transformador beta
14.
J Proteome Res ; 19(4): 1470-1480, 2020 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-32129075

RESUMEN

Due to its relatively small size, homology to humans, and susceptibility to human viruses, the tree shrew becomes an ideal alternative animal model for the study of human viral infectious diseases. However, there is still no report for the comprehensive glycan profile of the respiratory tract tissues in tree shrews. In this study, we characterized the structural diversity of N-glycans in the respiratory tract of tree shrews using our well-established TiO2-PGC chip-Q-TOF-MS method. As a result, a total of 219 N-glycans were identified. Moreover, each identified N-glycan was quantitated by a high sensitivity and accurate MRM method, in which 13C-labeled internal standards were used to correct the inherent run-to-run variation in MS detection. Our results showed that the N-glycan composition in the turbinate and lung was significantly different from the soft palate, trachea, and bronchus. Meanwhile, 28 high-level N-glycans in turbinate were speculated to be correlated with the infection of H1N1 virus A/California/04/2009. This study is the first to reveal the comprehensive glycomic profile of the respiratory tract of tree shrews. Our results also help to better understand the role of glycan receptors in human influenza infection and pathogenesis.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Tupaiidae , Animales , Glicómica , Humanos , Espectrometría de Masas , Polisacáridos , Titanio
15.
Ecotoxicol Environ Saf ; 200: 110779, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32460045

RESUMEN

Melon is of great value in food, medicine and industry. In recent years, the continuous cropping obstacles of melon is increasingly prominent, which seriously affects the cultivation. Autotoxicity is the key factor for the obstacles. Root is the first line against autotoxicity and main organs for autotoxins secretion. Some physiological responses and differentially expressed genes (DEGs) related to autotoxicity are only limited to root system. Considering the lack of relevant research, physiological researches combined with transcriptome sequencing of melon seedling after autotoxicity stress mediated by root exudates (RE) was performed to help characterize the response mechanism to autotoxicity in melon roots. The results showed that autotoxicity inhibited root morphogenesis of melon seedlings, induced the excessive accumulation of reactive oxygen species (ROS) and lipid peroxidation in roots, and activated most antioxidant enzymes. Compared with the control group, the osmoregulation substance content was always at a high level. DEGs response to autotoxicity in roots were distinguished from that in leaves. Functional annotation of these DEGs suggested that autotoxicity affected biological regulation in a negative manner. DEGs were mainly involved in the synthesis of antioxidants, DNA damage and metabolism, and stress response. These setbacks were associated with the deterioration of root morphogenesis, generation of dwarf and slender roots, and ultimately leading to plant death. The results may provide important information for revealing the response mechanism of root to autotoxicity, and provide theoretical basis for solving the continuous cropping obstacles in melon.


Asunto(s)
Producción de Cultivos/métodos , Cucumis melo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Raíces de Plantas/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Transcriptoma/efectos de los fármacos , Cucumis melo/genética , Cucumis melo/metabolismo , Perfilación de la Expresión Génica , Peroxidación de Lípido/efectos de los fármacos , Osmorregulación/efectos de los fármacos , Estrés Oxidativo/genética , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Plantones/efectos de los fármacos , Plantones/genética , Plantones/metabolismo
16.
Ecotoxicol Environ Saf ; 188: 109901, 2020 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-31704323

RESUMEN

Melon (Cucumis melo L.) is an important horticultural crop worldwide. Continuous cropping obstacle occurs in many melon cultivation area, resulting in poor plant growth and fruit quality, autotoxicity is the main reason for the obstacle. Silicon (Si) plays an important role in improving the resistance of plants to biotic and abiotic stresses. In this study, melon plant water extracts (MPWE) were used to simulate the autotoxicity stress. Different concentrations of Na2SiO3 (0, 1, 2, 4, 8, 16, 32 mM) were added into MPWE for preliminary concentration screening and alleviating effect determination of Si on melon seed autotoxicity. The results showed that autotoxicity reduced the seed germination index, inhibited the growth of germinated seeds. 2 mM Si significantly increased seed germination index and improved subsequent growth under autotoxicity. The effect of Si showed a concentration-dependent manner, which can be counteracted or even reversed at high concentration. Three treatment combinations, double distilled water, 0.02 g/mL MPWE and 2 mM Na2SiO3 + 0.02 g/mL MPWE were used for subsequent physiology, biochemistry and gene analysis. During the germination of melon seed under autotoxicity, starch degradation ability decreased, amylase activity and amylase gene expression were inhibited, cell membrane lipid peroxidation increased, and antioxidant enzyme activity was abnormal. In Si-addition group, the radicle growth, lateral roots number, starch degradation ability, amylase activity and amylase gene expression level increased. The addition of Si also maintained the activities of superoxide dismutase, catalase and peroxidase and the content of malondialdehyde in a relatively normal state. The change trend of amylase gene and antioxidant enzyme activity was complex, but the acute change coincided with the key stage of seed germination, which occurred when the seed was about to break through or just broken through the seed coat. Appropriate concentration of Si is an effective strategy to alleviate the autotoxicity on melon seed.


Asunto(s)
Cucurbitaceae/efectos de los fármacos , Cucurbitaceae/crecimiento & desarrollo , Germinación/efectos de los fármacos , Silicio/farmacología , Estrés Fisiológico/efectos de los fármacos , Antioxidantes/metabolismo , Cucurbitaceae/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Semillas/efectos de los fármacos , Semillas/crecimiento & desarrollo , Almidón/metabolismo
17.
BMC Cancer ; 18(1): 799, 2018 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-30089463

RESUMEN

BACKGROUND: Resistance to chemotherapy drugs (e.g. taxol) has been a major obstacle in successful cancer treatment. In A549 human lung adenocarcinoma, acquired resistance to the first-line chemotherapy taxol has been a critical problem in clinics. Sphingolipid (SPL) controls various aspects of cell growth, survival, adhesion, and motility in cancer, and has been gradually regarded as a key factor in drug resistance. To better understand the taxol-resistant mechanism, a comprehensive sphingolipidomic approach was carried out to investigate the sphingolipid metabolism in taxol-resistant strain of A549 cell (A549T). METHODS: A549 and A549T cells were extracted according to the procedure with optimal condition for SPLs. Sphingolipidomic analysis was carried out by using an UHPLC coupled with quadrupole time-of-flight (Q-TOF) MS system for qualitative profiling and an UHPLC coupled with triple quadrupole (QQQ) MS system for quantitative analysis. The differentially expressed sphingolipids between taxol-sensitive and -resistant cells were explored by using multivariate analysis. RESULTS: Based on accurate mass and characteristic fragment ions, 114 SPLs, including 4 new species, were clearly identified. Under the multiple reaction monitoring (MRM) mode of QQQ MS, 75 SPLs were further quantified in both A549 and A549T. Multivariate analysis explored that the levels of 57 sphingolipids significantly altered in A549T comparing to those of A549 (p < 0.001 and VIP > 1), including 35 sphingomyelins (SMs), 14 ceramides (Cers), 3 hexosylceramides (HexCers), 4 lactosylceramides (LacCers) and 1 sphingosine. A significant decrease of SM and Cer levels and overall increase of HexCer and LacCer represent the major SPL metabolic characteristic in A549T. CONCLUSIONS: This study investigated sphingolipid profiles in human lung adenocarcinoma cell lines, which is the most comprehensive sphingolipidomic analysis of A549 and A549T. To some extent, the mechanism of taxol-resistance could be attributed to the aberrant sphingolipid metabolism, "inhibition of the de novo synthesis pathway" and "activation of glycosphingolipid pathway" may play the dominant role for taxol-resistance in A549T. This study provides insights into the strategy for clinical diagnosis and treatment of taxol resistant lung cancer.


Asunto(s)
Células A549 , Resistencia a Antineoplásicos , Neoplasias Pulmonares/metabolismo , Paclitaxel/farmacología , Esfingolípidos , Células A549/química , Células A549/efectos de los fármacos , Células A549/metabolismo , Cromatografía Liquida , Biología Computacional , Humanos , Espectrometría de Masas , Análisis de Componente Principal , Esfingolípidos/análisis , Esfingolípidos/química , Esfingolípidos/metabolismo
18.
Pharmacol Res ; 137: 76-88, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30227260

RESUMEN

T lymphocytes produced by the thymus are essential mediators of immunity. Accelerated thymic atrophy appears in the patients with administration of glucocorticoids (GCs) which are commonly-used drugs to treat autoimmune and infectious diseases, leading to dysregulation of immunity with manifestation of progressive diminution of new T cell production. However, there is no ideal method to overcome such side effects of GCs. In the current study, we proposed a composition of dexamethasone (DEX) and dihydromyricetin (DMY) derived from a medicinal plant, which could protect from DEX-induced thymus damage and simultaneously enhance the anti-inflammatory effect of DEX. In the current study, we found that DEX-damaged thymic cellularity and architecture, reduced thymocyte numbers, induced thymocyte apoptosis and dropped CD4+ and CD8+ double positive T cell numbers in thymus which was effectively improved by co-treatment with DMY. Quantification of signal joint TCR delta excision circles (TRECs) and Vß TCR spectratyping analysis were employed to determine the thymus function with indicated treatments. The results showed that DEX-impaired thymus output and decreased TCR cell diversity which was ameliorated by co-treatment with DMY. iTRAQ 2D LC-MS/MS was applied to analyze the proteomic profiling of thymus of mice treated with or without indicated agents, followed by informatics analysis to identify the correlated signaling pathway. After validated by Western blotting and Real-time PCR, we found that PPARγ-associated fatty acid metabolism was increased in the thymic tissues of the animals treated with DMY plus DEX than the animals treated with DEX alone. The agonist and antagonist of PPARγ were further employed to verify the role of PPARγ in the present study. Furthermore, DMY demonstrated a synergistic effect with co-administration of DEX on suppressing inflammation in vivo. Collectively, DMY relieved thymus function damaged by DEX via regulation of PPARγ-associated fatty acid metabolism. Our findings may provide a new strategy on protection of thymus from damage caused by GCs by using appropriate adjuvant natural agents through up-regulation of PPARγ-associated fatty acid metabolism.


Asunto(s)
Antiinflamatorios/farmacología , Dexametasona/farmacología , Ácidos Grasos/metabolismo , Flavonoles/farmacología , Glucocorticoides/farmacología , PPAR gamma/metabolismo , Timo/efectos de los fármacos , Animales , Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Quimioterapia Combinada , Flavonoles/uso terapéutico , Glucocorticoides/uso terapéutico , Hipersensibilidad Tardía/tratamiento farmacológico , Ratones , Timo/metabolismo , Regulación hacia Arriba/efectos de los fármacos
19.
Zhongguo Zhong Yao Za Zhi ; 42(18): 3557-3563, 2017 Sep.
Artículo en Zh | MEDLINE | ID: mdl-29218942

RESUMEN

In this study, we used Ultra Performance Liquid Chromatography-Time-of-Flight Mass Spectrometry(UPLC-TOF-MS)to identify the chemical constituents in both ethanol and water extract of Polygonum capitatum. A Waters ACQUITY UPLC BEH C18 column(2.1 mm×100 mm,1.7 µm) was used for separation. The mobile phase was consisted of(A) 0.10% formic acid in water and(B)0.10% formic acid in acetonitrile, and the flow rate was 0.35 mL•min⁻¹. ESI source in negative ion mode was used for MS detection. Structural identification was carried out according to the accurate mass and matching with database. The results showed that flavonoids, polyphenols and lignans were the main components in both extracts. However, the chemical compositions of both extracts were different, e.g. there are less hydrolyzable tannins, loss of ellagic acid and more anthocyanins in ethanol extract. In a conclusion, this study provides an important scientific basis for identifying the active ingredients in P. capitatum, which also help to reveal the pharmacological effect of P. capitatum.


Asunto(s)
Medicamentos Herbarios Chinos/análisis , Extractos Vegetales/análisis , Polygonum/química , Cromatografía Líquida de Alta Presión , Etanol , Flavonoides/análisis , Lignanos/análisis , Polifenoles/análisis , Espectrometría de Masas en Tándem , Agua
20.
Chem Pharm Bull (Tokyo) ; 64(10): 1505-1508, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27725504

RESUMEN

Phytochemical investigation of the root of Baphicacanthus cusia (NEES) BREMEK afforded two new alkaloids, baphicacanthin A (1) and baphicacanthin B (2), along with 28 known compounds. The chemical structures of these compounds were elucidated on the basis of one and two dimensional (1D/2D)-NMR and high resolution (HR)-MS spectral evidence.


Asunto(s)
Acanthaceae/química , Alcaloides/química , Alcaloides/aislamiento & purificación , Benzoxazinas/química , Glucósidos/química , Alcaloides Indólicos/química , Fitoquímicos/química , Raíces de Plantas/química , Benzoxazinas/aislamiento & purificación , Glucósidos/aislamiento & purificación , Alcaloides Indólicos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura Molecular , Fitoquímicos/aislamiento & purificación
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