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1.
Med Sci Monit ; 27: e928758, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33439855

RESUMO

BACKGROUND We investigated the root canal curvature and morphology of maxillary posterior teeth in Guizhou, China, to provide references for clinical practice. MATERIAL AND METHODS We collected 274 maxillary posterior teeth in Guizhou Province, China. The root canal curvature was observed by X-ray film measurement. Two hundred teeth were selected to make transparent tooth models, and root canal configuration was recorded according to Vertucci classification criteria. The position of the MB2 root canal orifice and the mesiobuccal root canal configuration were observed by micro-computed tomographic (micro-CT) scanning. The t test and the chi-square test were used for statistical analysis. RESULTS The root canals of the maxillary posterior teeth showed more significant curvature in the mesiodistal direction than in the buccolingual direction (P<0.05). The MB2 root canal of maxillary molars showed severe bending in the mesiodistal direction: 25.16±6.6 degrees and 28.05±8.65 degrees in first and second molars, respectively. The detection rate of MB2 was 48% in maxillary first molars and 32% in maxillary second molars. The results of micro-CT showed that the vertical distances between the MB2 and MB-P line were 0.64±0.34 mm and 0.57±0.28 mm in first and second molars, respectively. CONCLUSIONS The root canal morphology and curvature of maxillary posterior teeth varied greatly in the Guizhou population, which increases the difficulty of treatment. It is necessary for clinicians to gain understanding of the root canal and to improve the success rate of root canal therapy.

2.
Br J Pharmacol ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33443775

RESUMO

BACKGROUND AND PURPOSE: Colorectal cancer (CRC) is the third most common cancer worldwide. HER2 and HER3 are two members of human epidermal receptor family of tyrosine kinase receptors (RTKs) and associated with poor survival in CRC. They have been observed as important therapeutic targets in various types of cancer. Corosolic acid (CRA), a natural pentacyclic triterpene has been demonstrated to have significant anticancer activity. However, the target of CRA has not yet been explored. This study aimed to reveal the direct targets of CRA underlying its anticancer activities. EXPERIMENTAL APPROACH: The targets of CRA were revealed by the phospho-RTK array, Bio-layer interferometry, co-immunoprecipitation and Proximity ligation assay. The inhibitory action of CRA on HER2/HER3 heterodimerization and related downstream signaling were investigated in HCT116 and SW480 cells. In addition, the chemopreventive effects of CRA were validated in both HCT116 xenograft model and AOM/DSS model. KEY RESULTS: Our results demonstrated that CRA could prevent NRG1-induced HER2/HER3 heterodimerization and suppress the phosphorylation of both HER2 and HER3. Furthermore, HER2 and HER3 could regulate the downstream signaling pathways of RalA/RalBP1/CDK1 and PI3K/Akt/PKA respectively, resulting in the changes in phosphorylation of Drp1 and mitochondrial dynamics. CRA exhibited anticancer activity in both HCT116 xenograft model and AOM/DSS model. CONCLUSIONS AND IMPLICATIONS: Collectively, our results demonstrated CRA directly targeted HER2 and HER3 heterodimerization and inhibited mitochondrial fission via regulating RalA/RalBP1/CDK1 and PI3K/Akt/PKA pathways, revealing a novel mechanism underlying the beneficial effects of CRA on CRC.

3.
J Pharm Biomed Anal ; 194: 113770, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33288343

RESUMO

Rhizoma Paridis (RP) with significant anti-tumor and haemostatic effects, has been used as the raw material of many Traditional Chinese preparations. However, its active ingredients are still unclear. The present study aimed to discover bioactive ingredients from RP based on spectrum-relationship and chemometric methods. Firstly, the saponins extract was prepared by phytochemical methods. Furthermore, UHPLC-QTOF-MS and UHPLC-qMS were incorporated to establish an efficient and sensitive method for obtaining the chemical profiles of RP. A total of 34 saponins were characterized in RP and 13 of them were assigned as common peaks in 25 batches of samples. After evaluation of the anti-tumor and haemostatic activities of samples, spectrum-effect relationships were investigated by the grey relational analysis (GRA), orthogonal projections to latent structures (OPLS) and back propagation artificial neural network (BP-ANN). These analyses showed that polyphyllin VII (P27), polyphyllin II (P30), dioscin (P31) and polyphyllin I (P33) play a role in the haemostatic effects of RP whereas polyphyllin VII (P27), dioscin (P31), polyphyllin I (P33), progenin III (P34) were assigned as candidate ingredients accounting for the anti-tumor activity of RP. The anti-tumor and haemostatic activities of these screened ingredients were subsequently verified in vitro. Collectively, the present study established the spectrum-effect relationship mode of RP and discovered the bioactive compounds of RP, which could be also used for exploration of bioactive compounds in herbal medicines, especially for trace compounds.

4.
BMC Genomics ; 21(1): 781, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172386

RESUMO

BACKGROUND: The members of the sucrose non-fermenting 1-related protein kinase 2 (SnRK2) family are specific serine/threonine protein kinases in plants that play important roles in stress signal transduction and adaptation. Because of their positive regulatory roles in response to adverse conditions, the genes encoding thes proteins are considered potential candidates for breeding of plants for disease resistance and genetic improvement. However, there is far less information about this kinase family, and the function of these genes has not been explored in Rosaceae. RESULTS: A genome-wide survey and analysis of the genes encoding members of the SnRK2 family were performed in pear (Pyrus bretschneideri) and seven other Rosaceae species. A total of 71 SnRK2 genes were identified from the eight Rosaceae species and classified into three subgroups based on phylogenetic analysis and structural characteristics. Purifying selection played a crucial role in the evolution of SnRK2 genes, and whole-genome duplication and dispersed duplication were the primary forces underlying the characteristics of the SnRK2 gene family in Rosaceae. Transcriptome data and qRT-PCR assay results revealed that the distribution of PbrSnRK2s was very extensive, including across the roots, leaves, pollen, styles, and flowers, although most of them were mainly expressed in leaves. In addition, under stress conditions, the transcript levels of some of the genes were upregulated in leaves in response to ABA treatment. CONCLUSIONS: This study provides useful information and a theoretical introduction for the study of the evolution, expression, and functions of the SnRK2 gene family in plants.

5.
Huan Jing Ke Xue ; 41(8): 3765-3772, 2020 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124352

RESUMO

The effective inhibition of nitrite oxidizing bacteria (NOB) is the key to realizing satisfactory nitrite accumulation and achieving effective nitritation. In order to explore the selective effect of hydroxylamine (NH2 OH) on ammonia oxidizing bacteria (AOB) and NOB, a sequencing batch reactor (SBR) with the operation mode of anaerobic/aerobic/anoxia (A/O/A) was used to observe the start-up of nitritation at different concentrations and frequencies of NH2 OH. The results showed that when 5 mg·L-1 of NH2 OH was added once every 2 cycles, the nitrite accumulation rate (NAR) increased from 0.1% to 57.4% in 6 days, and was maintained at (62.0±4.6)% until the end of the trials. In the typical cycle on day 6, the NN4+-N dropped from 26.05 mg·L-1 to 8.06 mg·L-1, thus producing 9.02 mg·L-1 of NO2--N and 6.70 mg·L-1 of NO3--N. Meanwhile, the ratio of the maximum activity of AOB (rAOB) to NOB (rNOB) increased from 1.05 on day 1 to 4.22 on day 9. Moreover, qPCR results indicated that the abundance of AOB and NOB decreased to 30.2% and 19.1%, respectively, on day 9 in comparison to the original sample. The results indicate that the selective effect of AOB and NOB based on NH2 OH is expected to provide a feasible application for the rapid start-up nitritation of municipal wastewater.


Assuntos
Amônia , Nitritos , Bactérias/genética , Reatores Biológicos , Hidroxilamina , Hidroxilaminas , Nitrificação , Oxirredução , Esgotos
6.
Appl Opt ; 59(28): 8540-8552, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33104532

RESUMO

Digital holographic microscopy (DHM) suffers from a limited refocus depth range due to the employed microscope objective. The relationship between the refocus depth range of the DHM system and its optical parameters is studied theoretically and experimentally, and a method is proposed that combines wavefront coding with bicubic interpolation and extrapolation iteration to extend the refocus depth range. For obtaining a uniform point spread function on the refocus plane, a propagator kernel in numerical reconstruction is multiplied by a numerical logarithmic phase mask, and a deviation of the refocus distance is made. To improve the resolution of the refocused image, the size of the hologram is doubly enlarged. This approach can extend the refocus depth range from 0.9 up to 1.5 mm. This work provides important guidance for high-resolution imaging with a large refocus depth range in DHM.

7.
Front Immunol ; 11: 1721, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072064

RESUMO

Over the past 10 years, cancer immunotherapy has made significant progress in multiple cancer types and has been gradually been applied to clinical cancer care, in which the programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is one of the most attractive targets. Compared with traditional therapies, the emerging PD-1/PD-L1 blockade immunotherapy exhibited more satisfactory curative effects and lower toxicity for patients with advanced head and neck squamous cell carcinoma (HNSCC). This review analyzes the expression characteristics and clinical significance of PD-1/PD-L1 in HNSCC, the immunosuppressive roles of tumor cell and stromal cell expressing PD-1/PD-L1 in this disease, and presents the development landscape of PD-1/PD-L1 inhibitors, which may provide new curative alternatives for recurrent or metastatic HNSCC.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33108720

RESUMO

Solar steam generation is receiving considerable interest because of its potential application in wastewater treatment and desalination. Many devices with various photothermal materials and structures have been demonstrated to be solar steam evaporators by improving their light absorption, heat loss, water transportation, and vapor escape. However, developing a biomass-based evaporator with heat localization and rapid water transportation is highly desired yet still challenging. Here, corncobs, a kind of agricultural waste with vascular bundle and "vesiculose" structures, are used to fabricate solar steam-generation devices. After high-temperature treatment, the carbonized corncobs maintain the highly anisotropic porous framework and favorable hydrophilicity and thereby have excellent thermal management and water transportation. With efficient solar absorption, heat localization, and rapid water transportation, the lightweight carbonized corncobs can float on water and generate water vapor with a high steam generation efficiency of 86.7% under 1 sun.

9.
BMC Genomics ; 21(1): 612, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894061

RESUMO

BACKGROUND: Lysin motif-containing proteins (LYP), which act as pattern-recognition receptors, play central roles in growth, node formation, and responses to biotic stresses. The sequence of Chinese white pear genome (cv. 'Dangshansuli') along with the seven other species of Rosaceae has already been reported. Although, in these fruit crops, there is still a lack of clarity regarding the LYP family genes and their evolutionary history. RESULTS: In the existing study, eight Rosaceae species i.e., Pyrus communis, Prunus persica, Fragaria vesca, Pyrus bretschneideri, Prunus avium, Prunus mume, Rubus occidentalis, and Malus × domestica were evaluated. Here, we determined a total of 124 LYP genes from the underlined Rosaceae species. While eighteen of the genes were from Chinese white pear, named as PbrLYPs. According to the LYPs structural characteristics and their phylogenetic analysis, those genes were classified into eight groups (group LYK1, LYK2, LYK3, LYK4/5, LYM1/3, LYM2, NFP, and WAKL). Dispersed duplication and whole-genome duplication (WGD) were found to be the most contributing factors of LYP family expansion in the Rosaceae species. More than half of the duplicated PbrLYP gene pairs were dated back to the ancient WGD (~ 140 million years ago (MYA)), and PbrLYP genes have experienced long-term purifying selection. The transcriptomic results indicated that the PbrLYP genes expression was tissue-specific. Most PbrLYP genes showed differential expression in leaves under fungal pathogen infection with two of them located in the plasmalemma. CONCLUSION: A comprehensive analysis identified 124 LYP genes in eight Rosaceae species. Our findings have provided insights into the functions and characteristics of the Rosaceae LYP genes and a guide for the identification of other candidate LYPs for further genetic improvements for pathogen-resistance in higher plants.

10.
J Org Chem ; 85(21): 13517-13528, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-32988207

RESUMO

A facile and expeditious protocol for the synthesis of 2-arylindole compounds from readily available N-(2-pyridyl)anilines and commercially available α-Cl ketones through iridium-catalyzed C-H activation and cyclization is reported here. As a complementary approach to the conventional strategies for indole synthesis, the transformation exhibits powerful reactivity, tolerates a large number of functional groups, and proceeds with good to excellent yields under mild conditions, providing a straightforward method to obtain structurally diverse and valuable indole scaffolds. Furthermore, the reaction could be easily scaled up to gram scale.

11.
Int J Oncol ; 57(4): 1001-1012, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945386

RESUMO

Long non­coding RNAs (lncRNAs) serve a pivotal role in hepatocellular carcinoma (HCC) progression and have been confirmed to participate in the carcinogenesis and development of HCC. Certain studies have focused on lncRNA nuclear enriched abundant transcript 1 (NEAT1) in HCC. However, the relationship between lncRNA NEAT1 and HCC remains unclear. The present study found that NEAT1 was significantly overexpressed in HCC cell lines compared with LX­2 hepatic stellate cells. NEAT1 expression in Huh7 and MHCC­97H cells was increased following transfection with lentivirus (LV)­NEAT1 but inhibited by LV­short hairpin NEAT1. Knockdown of NEAT1 significantly repressed HCC cell viability, increased cell apoptosis, and inhibited cell migration and invasion capacity. By contrast, upregulation of NEAT1 demonstrated the reverse effects. Furthermore, microRNA­320a (miR­230a) was predicted to be a direct target of NEAT1 and was significantly reduced in HCC cells. Additionally, a luciferase activity reporter assay and RNA immunoprecipitation assay were performed to confirm the interaction between miR­320a and NEAT1. Using a dual­luciferase activity assay, L antigen family member 3 (LAGE3) was found to be a target of miR­320a. Finally, in vivo nude mouse models were established, and the results indicated that NEAT1 suppressed HCC progression by targeting miR­320a. In conclusion, the present findings revealed that the NEAT1/miR­320a/LAGE3 axis participates in HCC development and that NEAT1 could be used as a biomarker for HCC.

12.
Commun Biol ; 3(1): 416, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737399

RESUMO

DNA emerged as a novel potential material for mass data storage, offering the possibility to cheaply solve a great data storage problem. Large oligonucleotide pools demonstrated high potential of large-scale data storage in test tube, meanwhile, living cell with high fidelity in information replication. Here we show a mixed culture of bacterial cells carrying a large oligo pool that was assembled in a high-copy-number plasmid was presented as a stable material for large-scale data storage. The underlying principle was explored by deep bioinformatic analysis. Although homology assembly showed sequence context dependent bias, the large oligonucleotide pools in the mixed culture were constant over multiple successive passages. Finally, over ten thousand distinct oligos encompassing 2304 Kbps encoding 445 KB digital data, were stored in cells, the largest storage in living cells reported so far and present a previously unreported approach for bridging the gap between in vitro and in vivo systems.

13.
Med Sci Monit ; 26: e922794, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32810082

RESUMO

BACKGROUND To investigate variations in the anatomy of root canals in permanent second molars of the upper jaw in a population in Chongqing, China, using cone-beam computed tomography (CBCT). MATERIAL AND METHODS CBCT imaging data of 400 second permanent molars of the upper jaws of 200 patients were retrospectively reviewed. Patients' gender, age, numbers of roots and canals, root fusion of permanent second molars of the maxilla on both sides, and morphological categories of root canals of mesiobuccal roots were recorded. The distances from the apices of the distobuccal and mesiobuccal roots to the buccal bone plate were measured. RESULTS Of the 400 permanent second maxillary molars, 312 (78.0%) had three roots and 247 (61.75%) had three canals. Fused roots were observed in 126 (31.5%) teeth; of these, 67 (53.2%) had three canals and 44 (34.9%) had two canals. Morphologically, 297 (74.25%), 29 (7.25%), nine (2.25%) and 65 (16.25%) teeth had type I, II, III, and IV mesiobuccal root canals, respectively, with 103 (25.75%) having secondary mesiobuccal canals. The distances from the apices of the mesiobuccal, distobuccal, and single buccal roots to the surface of the buccal osseous lamella were 7.34±1.89 mm, 6.26±1.74 mm, and 8.60±2.56 mm, respectively. CONCLUSIONS The root form and canal shape of permanent second molars of the upper jaw varied greatly among the population of Chongqing, China. CBCT is a valuable method for assessing the complex anatomic morphology of teeth.

14.
Curr Biol ; 30(18): 3591-3603.e8, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32822611

RESUMO

Subanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine's effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces downregulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus, ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.

15.
BMC Oral Health ; 20(1): 224, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807171

RESUMO

BACKGROUND: The aim of this study was to investigate the prevalence of the middle mesial canal (MMC) and radix entomolaris (RE) in mandibular first permanent molars in a western Chinese population using cone-beam computed tomography (CBCT). METHODS: A total of 1174 CBCT images of the mandibular first molars were collected from West China Hospital of Stomatology, Sichuan University. The following information was recorded and evaluated: the detection rate and location of the MMC and RE, the curvature of the RE, the canal configuration and bilateral symmetry. RESULTS: The detection rates of the MMC and RE were 3.41 and 25.04%, respectively, as calculated by individuals, and 1.79 and 22.15%, respectively, as calculated by total teeth. The average curvature in the buccolingual (BL) orientation (40.63 ± 14.39°) was significantly larger than that in the mesiodistal (MD) orientation (17.64 ± 7.82°) (p < 0.05). Of 587 patients, 71.72% (421/587) had bilateral symmetry according to the root canal morphology. The prevalence of three-rooted mandibular first molars was higher in males than in females, while the prevalence of two-rooted mandibular first molars was higher in females than in males. CONCLUSIONS: Our results showed that the RE could be detected in almost 1/4 of the western Chinese population; thus, RE detection requires special attention and careful assessment in endodontic treatment.


Assuntos
Cavidade Pulpar , Mandíbula , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Tomografia Computadorizada de Feixe Cônico , Cavidade Pulpar/anatomia & histologia , Cavidade Pulpar/diagnóstico por imagem , Feminino , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Dente Molar/anatomia & histologia , Dente Molar/diagnóstico por imagem , Prevalência , Raiz Dentária/anatomia & histologia , Raiz Dentária/diagnóstico por imagem
16.
Bioresour Technol ; 312: 123590, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32504950

RESUMO

In the anammox process treating low-strength municipal wastewater, the effect of common seasonal temperature variation (15.1 °C-22.2 °C) on performance was studied. In autumn and winter, the nitrogen removal rate (NRR) decrement of 0.038kgN/(m3·d) (17.9 °C â†’ 15.1 °C) was nearly threefold higher than 0.014kgN/(m3·d) (22.2 °C â†’ 17.9 °C), which showed that lower temperature laid more negative impact on nitrogen removal. 15N isotope tracing tests confirmed that the contribution of denitrification to nitrogen removal was far less than anammox, and anammox contributed more at 15.1 °C (91.7%) than 21.9 °C (78.9%). Anammox bacteria could adapt to lower temperature after short-term acclimatization, especially the dominant genus Ca. Brocadia increased from 1.8% to 2.5% and its abundance was significantly correlated with nitrogen consumption (p < 0.05). Above findings suggest that the adaptability of Ca. Brocadia could provide the possibility to maintain nitrogen removal performance at lower temperature. In spring, the improved maximum anammox activity from 2.85 to 3.23mgNH4+-N/(gVSS·h) indicated the recovered removal capacity.


Assuntos
Reatores Biológicos , Águas Residuárias , Anaerobiose , Desnitrificação , Nitrogênio , Oxirredução , Estações do Ano , Temperatura
17.
J Exp Clin Cancer Res ; 39(1): 102, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493454

RESUMO

BACKGROUND: Human papillomavirus (HPV)-positive oral squamous cell carcinoma (OSCC) is increasing worldwide with typically higher grade and stage, while better prognosis. microRNAs (miRNAs) has been shown to play a critical role in cancer, however, their role in HPV-positive OSCC progression remains unclear. METHODS: miRNA microarray was performed to identify differentially expressed miRNAs. qRT-PCR and FISH were performed to determine the relative expression of miR-550a-3-5p. CCK-8, Flow cytometry, Wound healing, Cell invasion assays and xenograft experiments were conducted to analyze the biological roles of miR-550a-3-5p. Tumor-associated macrophages (TAMs) generation, co-culturing of cancer cells with TAMs, Western blot, Dual-luciferase reporter gene assay, Immunohistochemistry and animal studies were performed to explore the mechanisms underlying the functions of miR-550a-3-5p. RESULTS: We identified 19 miRNAs differentially expressed in HPV-positive OSCC specimens and miR-550a-3-5p was down-regulated. The low expression of miR-550a-3-5p correlated with higher tumor size and nodal metastasis of HPV-positive OSCC patients. Then, we found that miR-550a-3-5p suppressed the migration, invasion and EMT of HPV-positive OSCC cells dependent on decreasing M2 macrophages polarization. Moreover, miR-550a-3-5p, down-regulated by E6 oncoprotein, inhibited M2 macrophages polarization by YAP/CCL2 signaling, which in turn abrogating EMT program in HPV-positive OSCC cells. In addition, in both xenografts and clinical HPV-positive OSCC samples, miR-550a-3-5p levels were inversely associated with YAP, CCL2 expressions and the number of M2 macrophages. CONCLUSIONS: E6/miR-550a-3-5p/YAP/CCL2 signaling induces M2 macrophages polarization to enhance EMT and progression, revealing a novel crosstalk between cancer cells and immune cells in HPV-positive OSCC microenvironment.

18.
Genomics ; 112(5): 3484-3496, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32585175

RESUMO

Alcohol dehydrogenase (ADH) is essential to the formation of aromatic compounds in fruits. However, the evolutionary history and characteristics of ADH gene expression remain largely unclear in Rosaceae fruit species. In this study, 464 ADH genes were identified in eight Rosaceae fruit species, 68 of the genes were from pear and which were classified into four subgroups. Frequent single gene duplication events were found to have contributed to the formation of ADH gene clusters and the expansion of the ADH gene family in these eight Rosaceae species. Purifying selection was the major force in ADH gene evolution. The younger genes derived from tandem and proximal duplications had evolved faster than those derived from other types of duplication. RNA-Seq and qRT-PCR analysis revealed that the expression levels of three ADH genes were closely correlated with the content of aromatic compounds detected during fruit development.

19.
Clin Rheumatol ; 39(12): 3723-3732, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32447600

RESUMO

OBJECTIVE: Adult-onset Still's disease (AOSD) is an autoinflammatory disorder leading to multiorgan involvements. We sought to investigate mood status and the health-related quality of life (HRQoL) in these patients. METHODS: In this study, 82 AOSD patients and 82 age- and sex-matched healthy controls were included. Demographic and clinical data of recruited patients were collected. The Hospital Anxiety and Depression Scale (HADS) and Medical Outcomes Survey Short Form-36 (SF-36) were used to evaluate the mood status and quality of life, respectively. Spearman correlation and multivariable linear regression analyses were used to assess the disease-related risk factors associated with anxiety and depression. RESULTS: Forty-four active and thirty-eight relieved patients were enrolled. We found that scores of both HADS anxiety (HADS-A) and depression (HADS-D) subscales in active AOSD were significantly higher than inactive patients, which were significantly higher than controls. Moreover, the HADS-A was positively correlated to the patient's global assessment (PGA), pain, and dosage of prednisone, and the HADS-D was positively correlated to systemic score, PGA, and pain. Female, high dosage of corticosteroids, and PGA more than 50 had a significant association with HADS-A score, while the sore throat and PGA more than 50 had a significant association with HADS-D score. Furthermore, AOSD patients' anxiety and depression had a negative impact on HRQoL. CONCLUSION: Active AOSD patients tended to be anxious and depressed, suffering from poorer HRQoL compared to patients in remission. Therefore, the evaluation of mental health and HRQoL should be included in AOSD patients' long-term management. Key Points • Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder leading to multiorgan involvement. This study was so far the first published research focuses on AOSD patients' mental involvement and health-related quality of life (HRQoL). • Active AOSD patients were more tended to be anxious and depressive and suffered from poorer HRQoL compared to inactive patients. • Patients' anxiety and depression were associated with impaired HRQoL.

20.
J Med Chem ; 63(11): 6096-6106, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32401032

RESUMO

Multitargeted therapy could rectify various oncogenic pathways to block tumorigenesis and progression. The combination of endocrine-, immune-, and chemotherapy might exert a highly synergistic effect against certain tumors. Herein, a series of smart Pt(IV) prodrugs 3-6, named Melatplatin, were rationally designed not only to multitarget DNA, MT1, and estrogen receptor (ER) but also to activate immune response. Melatplatin, conjugating first-line chemotherapeutic Pt drugs with human endogenous melatonin (MT), significantly enhanced drug efficacy especially in ER high-expression (ER+) cells, among which 3 presented the most potent cytotoxicity toward ER+ MCF-7 with nanomolar IC50 values 100-fold lower than cisplatin. Melatplatin could bind well to melatonin receptor (MT1) according to molecular docking. Besides, 3 evidently increased intracellular accumulation and DNA damage, upregulated γH2AX and P53, and silenced NF-κB to induce massive apoptosis. Most strikingly, 3 effectively inhibited tumor growth and attenuated systemic toxicity compared to cisplatin in vivo, promoting lymphocyte proliferation in spleen to achieve immune modulation.


Assuntos
Antineoplásicos/química , Platina/química , Pró-Fármacos/química , Receptor MT1 de Melatonina/metabolismo , Receptores Estrogênicos/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Sítios de Ligação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Camundongos , Camundongos Nus , Simulação de Acoplamento Molecular , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Estrutura Terciária de Proteína , Receptor MT1 de Melatonina/química , Receptores Estrogênicos/química
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