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1.
Front Pharmacol ; 13: 875700, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559233

RESUMO

Background: The incidence of Nonalcoholic Fatty Liver (NAFL) is increasing year by year, growing evidence suggests that the intestinal flora plays a causative role in NAFL. Huazhi Rougan Granule (HRG) is commonly used in the clinical treatment of NAFL. It is reported that it can reduce lipids and protect the liver, but no research has confirmed whether the drug's effect is related to the intestinal flora. Therefore, we investigated whether the effect of HRG is related to the regulation of intestinal flora to further explore the mechanism of HRG in the treatment of NAFL through intestinal flora. Methods: In this study, C57BL/6J mice were fed a high-fat diet for 8 weeks, and the high-fat diet plus HRG or polyene phosphatidylcholine capsules were each administered by gavage for 4 weeks. High-throughput sequencing, network pharmacology, and molecular docking were used to explore the mechanism of HRG in the treatment of NAFL through intestinal flora. Results: HRG treatment can reduce body weight gain, lipid accumulation in liver and lipogenesis and reduce serum biochemical indexes in high-fat-fed mice. Analysis of intestinal flora showed that HRG changed the composition of intestinal flora, which was characterized by a decrease in the Firmicutes/Bacteroidetes ratio. Moreover, the species distribution was significantly correlated with AKP, HDL-C, and TG. Metagenetic analysis showed that HRG altered the functional composition and functional diversity of microorganisms, which was mainly characterized by an increase in the abundance of metabolic pathways. The network pharmacology results show that the mechanism of HRG in the treatment of NAFL through intestinal flora is mainly reflected in the biological process of gene function and related to infectious diseases, immune systems, and signal transduction pathways, such as cytokine-cytokine receptor interaction, Chagas disease, IL-17 signaling pathway and other signaling pathways. Conclusion: These results strongly suggest that HRG may alleviate NAFL by preventing IFD.

2.
mBio ; : e0109922, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536005

RESUMO

Human metapneumovirus (HMPV) inclusion bodies (IBs) are dynamic structures required for efficient viral replication and transcription. The minimum components needed to form IB-like structures in cells are the nucleoprotein (N) and the tetrameric phosphoprotein (P). HMPV P binds to the following two versions of the N protein in infected cells: N-terminal P residues interact with monomeric N (N0) to maintain a pool of protein to encapsidate new RNA and C-terminal P residues interact with oligomeric, RNA-bound N (N-RNA). Recent work on other negative-strand viruses has suggested that IBs are, at least in part, liquid-like phase-separated membraneless organelles. Here, HMPV IBs in infected or transfected cells were shown to possess liquid organelle properties, such as fusion and fission. Recombinant versions of HMPV N and P proteins were purified to analyze the interactions required to drive phase separation in vitro. Purified HMPV P was shown to form liquid droplets in isolation. This observation is distinct from other viral systems that also form IBs. Partial removal of nucleic acid from purified P altered phase-separation dynamics, suggesting that nucleic acid interactions play a role in IB formation. HMPV P also recruits monomeric N (N0-P) and N-RNA to droplets in vitro. These findings suggest that HMPV P may also act as a scaffold protein to mediate multivalent interactions with monomeric and oligomeric N, as well as RNA, to promote phase separation of IBs. Together, these findings highlight an additional layer of regulation in HMPV replication by the viral P and N proteins. IMPORTANCE Human metapneumovirus (HMPV) is a leading cause of respiratory disease among children, immunocompromised individuals, and the elderly. Currently, no vaccines or antivirals are available for the treatment of HMPV infections. Cytoplasmic inclusion bodies (IBs), where HMPV replication and transcription occur, represent a promising target for the development of novel antivirals. The HMPV nucleoprotein (N) and phosphoprotein (P) are the minimal components needed for IB formation in eukaryotic cells. However, interactions that regulate the formation of these dynamic structures are poorly understood. Here, we showed that HMPV IBs possess the properties of liquid organelles and that purified HMPV P phase separates independently in vitro. Our work suggests that HMPV P phase-separation dynamics are altered by nucleic acid. We provide strong evidence that, unlike results reported from other viral systems, HMPV P alone can serve as a scaffold for multivalent interactions with monomeric (N0) and oligomeric (N-RNA) HMPV N for IB formation.

3.
Lupus ; : 9612033221100908, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536913

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) is a female-dominated autoimmune disease that can occur at any age and has a diverse course. The clinical manifestation of this disease can vary depending on the patient's age at onset. The aim of this study was to characterise the comorbidities at the time of SLE diagnosis and after in different age groups. METHODS: A total 1042 incident cases of SLE with a Catastrophic Illness Card in 2005 and 10,420 age- and sex-matched controls from the general population registered in the National Health Insurance Research Database in Taiwan were enrolled in the study. The risk of comorbidities before (adjusted odds ratio, [aOR]) and after (adjusted hazard ratio, [aHR]) of SLE was analysed. The burden of these SLE-associated comorbidities was weight by the Charlson comorbidity index (CCI). We used the cumulative incidence to evaluate the impact of comorbidities on different age onset groups. RESULTS: In this study, musculoskeletal diseases had the highest positive association (aOR, 5.29; 95% confidence interval [CI]: 4.25-6.57) prior to the diagnosis of SLE and they were also the most common developing incident comorbidity after the diagnosis (HR, 13.7; 95% CI: 11.91-15.77). It only took less than 1 year for 50% of the late-onset SLE patients to develop any increase in CCI score. The developing comorbidities attributed to 16.3% all-cause mortality and they had the greatest impact on late-onset SLE patients, with 33.3% cumulative incidence to all-cause mortality. There is no difference in the incidence of infectious diseases across different age groups. The herpes zoster infection had the greatest cumulative incidence among the category of infection diseases in child-onset SLE patients. CONCLUSION: SLE patients had increased risks of multiple pre-existing comorbidities at diagnosis. The developed comorbidity after diagnosis could contribute to all-cause mortality. The herpes zoster infection is primarily an issue in child-onset SLE patients.

4.
Front Psychiatry ; 13: 860487, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573385

RESUMO

Background: Mental illness diagnostic criteria are made based on assumptions. This pilot study aims to assess the public's perspectives on mental illness diagnoses and these assumptions. Methods: An anonymous survey with 30 questions was made available online in 2021. Participants were recruited via social media, and no personal information was collected. Ten questions focused on participants' perceptions regarding mental illness diagnoses, and 20 questions related to the assumptions of mental illness diagnoses. The participants' perspectives on these assumptions held by professionals were assessed. Results: Among 14 survey participants, 4 correctly answered the relationships of 6 symptom pairs (28.57%). Two participants could not correctly conduct the calculations involved in mood disorder diagnoses (14.29%). Eleven (78.57%) correctly indicated that 2 or more sets of criteria were available for single diagnoses of mental illnesses. Only 1 (7.14%) correctly answered that the associations between symptoms and diagnoses were supported by including symptoms in the diagnostic criteria of the diagnoses. Nine (64.29%) correctly answered that the diagnosis variances were not fully explained by their symptoms. The confidence of participants in the major depressive disorder diagnosis and the willingness to take medications for this diagnosis were the same (mean = 5.50, standard deviation [SD] = 2.31). However, the confidence of participants in the symptom-based diagnosis of non-solid brain tumor was significantly lower (mean = 1.62, SD = 2.33, p < 0.001). Conclusion: Our study found that mental illness diagnoses are wrong from the perspectives of the public because our participants did not agree with all the assumptions professionals make about mental illness diagnoses. Only a minority of our participants obtained correct answers to the calculations involved in mental illness diagnoses. In the literature, neither patients nor the public have been engaged in formulating the diagnostic criteria of mental illnesses.

5.
Front Plant Sci ; 13: 859386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574076

RESUMO

Sedum plumbizincicola (Crassulaceae), a cadmium (Cd)/zinc (Zn)/lead (Pb) hyperaccumulator native to Southeast China, is potentially useful for the phytoremediation of heavy metal-contaminated soil. Basic leucine zipper (bZIP) transcription factors play vital roles in plant growth, development, and abiotic stress responses. However, there has been minimal research on the effects of Cd stress on the bZIP gene family in S. plumbizincicola. In this study, 92 SpbZIP genes were identified in the S. plumbizincicola genome and then classified into 12 subgroups according to their similarity to bZIP genes in Arabidopsis. Gene structure and conserved motif analyses showed that SpbZIP genes within the same subgroup shared similar intron-exon structures and motif compositions. In total, eight pairs of segmentally duplicated SpbZIP genes were identified, but there were no tandemly duplicated SpbZIP genes. Additionally, the duplicated SpbZIP genes were mainly under purifying selection pressure. Hormone-responsive, abiotic and biotic stress-responsive, and plant development-related cis-acting elements were detected in the SpbZIP promoter sequences. Expression profiles derived from RNA-seq and quantitative real-time PCR analyses indicated that the expression levels of most SpbZIP genes were upregulated under Cd stress conditions. Furthermore, a gene co-expression network analysis revealed that most edge genes regulated by hub genes were related to metal transport, responses to stimuli, and transcriptional regulation. Because its expression was significantly upregulated by Cd stress, the hub gene SpbZIP60 was selected for a functional characterization to elucidate its role in the root response to Cd stress. In a transient gene expression analysis involving Nicotiana benthamiana leaves, SpbZIP60 was localized in the nucleus. The overexpression of SpbZIP60 enhanced the Cd tolerance of transgenic Arabidopsis plants by inhibiting ROS accumulation, protecting the photosynthetic apparatus, and decreasing the Cd content. These findings may provide insights into the potential roles of the bZIP family genes during the S. plumbizincicola response to Cd stress.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35545509

RESUMO

Ionic (2e - ) nucleophilic addition of allyl-metal regents to imines dominates the synthesis of homo-allyl amine, however single electron (1e - ) mediated imine allylation with feedstocks butadiene as alternative allyl source remains unexplored. In this work, we reported a conceptually different radical-radical cross-coupling strategy for the synthesis of homoallyl amine between an α-amino alkyl radical and a transient allylic radical. This metal-free method provided an novel approach for the synthesis of homoallylic amines (> 80 examples) from readily available materials with excellent regioselectivity and exceptional broad functional group compatibility.

7.
Int J Immunopathol Pharmacol ; 36: 3946320221099073, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35594865

RESUMO

OBJECTIVES: Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) can affect health status, hospitalization and readmission rates, and disease progression. This study aimed to identify independent markers associated with COPD AEs. METHODS: This study included male patients with COPD and collected data regarding their AEs and baseline clinical parameters. RESULTS: We included 149 male patients. Among them, 58 were included in the year 0 high-AE group and 91 in the low-AE group. Multivariate analysis revealed that the high-AE group had higher white blood cell count, lower serum albumin level, and post-bronchodilator (BD) forced expiratory volume in one second (FEV1) (%) with a combined receiver operating characteristic curve (ROC) of 0.721 (p < 0.001). Additionally, 34 patients were included in the year 1 high-AE group and 70 in the low-AE group (p < 0.001). Multivariate analysis revealed that the high-AE group had higher platelet count, positive asthma history, and lower pre-BD FEV1 (%) with a combined ROC of 0.782 (p < 0.001). CONCLUSION: In male patients with COPD, baseline white blood cell count, albumin level, and post-BD FEV1 (%) were correlated with year 0 AE; on the other hand, baseline platelet count, positive asthma history, and pre-BD FEV1 (%) were associated with year 1 AE.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Progressão da Doença , Volume Expiratório Forçado , Humanos , Contagem de Leucócitos , Masculino , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico
8.
Taiwan J Obstet Gynecol ; 61(3): 525-527, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35595451

RESUMO

OBJECTIVE: We present perinatal cytogenetic discrepancy in a pregnancy with mosaic 45,X/46, XY at amniocentesis and a favorable outcome. CASE REPORT: A 38-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[2]/46,XY[6]. Level II ultrasound at 20 weeks of gestation was unremarkable, and the fetus had normal male external genitalia. Following genetic counseling, the woman decided to continue the pregnancy. At 39 weeks of gestation, a healthy male baby was delivered with a body weight of 3410 g and a body length of 54.5 cm. The male external genital organs were normal. The cord blood had a karyotype of 46, XY (40/40 cells). The umbilical cord had a karyotype of 45,X[1]/46,XY[39]. During follow-up at age one month, his body weight was 4.4 Kg (15th-50th centile), and his body length was 56 cm (50th-85th centile). The infant was doing well. Interphase fluorescence in situ hybridization analysis on 100 buccal mucosal cells revealed no abnormal Y-deletion cell, and all cells contained one Y signal. CONCLUSION: Perinatal cytogenetic discrepancy may occur in the pregnancy with mosaic 45,X/46, XY at amniocentesis.


Assuntos
Amniocentese , Mosaicismo , Adulto , Peso Corporal , Hibridização Genômica Comparativa , Análise Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Gravidez , Trissomia
9.
Emerg Microbes Infect ; : 1-44, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35608053

RESUMO

The waning humoral immunity and emerging contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants resulted in the necessity of the booster vaccination of coronavirus disease 2019 (COVID-19). The inactivated vaccine, CoronaVac, is the most widely supplied COVID-19 vaccine globally. Whether the CoronaVac booster elicited adaptive responses that cross-recognize SARS-CoV-2 variants of concern (VoCs) among 77 healthy subjects receiving the third dose of CoronaVac was explored. After the boost, remarkable elevated spike-specific IgG and IgA responses, as well as boosted neutralization activities were observed, despite 3.0-fold and 5.9-fold reduced neutralization activities against Delta and Omicron strains compared to that of the ancestral strain. Furthermore, the booster dose induced potent B cells and memory B cells that cross-bound receptor binding domain (RBD) proteins derived from VoCs, while Delta and Omicron RBD-specific memory B cell recognitions were reduced by 2.7-fold and 4.2-fold compared to that of ancestral strain, respectively. Consistently, spike-specific circulating follicular helper T cells (cTfh) significantly increased and remained stable after the boost, with a predominant expansion towards cTfh17 subpopulations. Moreover, SARS-CoV-2-specific CD4+ and CD8+ T cells peaked and sustained after the booster. Notably, CD4+ and CD8+ T cell recognition of VoC spike was largely preserved compared to the ancestral strain. Individuals without generating Delta or Omicron neutralization activities had comparable levels of CD4+ and CD8+ T cells responses as those with detectable neutralizing activities. Our study demonstrated that the CoronaVac booster induced broad and potent adaptive immune responses that could be effective in controlling SARS-CoV-2 Delta and Omicron variants.

10.
Neurol Sci ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562557

RESUMO

BACKGROUND: Duchenne muscular dystrophy (DMD/Duchenne) is a progressive X-linked muscular disease with an overall incidence of 1:5,000 live male births. Recent availability in treatment for DMD raised the need of early diagnosis, and DMD became as a selective item of newborn screening (NBS) since Feb. 2021 in our center. MATERIALS AND METHODS: Dried blood spots (DBS) muscle-type creatine kinase (CK) isoform was measured with a commercialized kit with age-adjusted cutoffs. Subjects with an elevation of CK in the first screen were requested for a re-screen 2 weeks later. A DBS whole-exome sequencing (WES) panel for dystrophin and other neuromuscular-related genes was applied to confirm the diagnosis for subjects with persistent hyperCKemia. RESULTS: During a 1-year period, 50,572 newborns (male 26,130) received DMD screening at a mean age of 2 days (SD 1 day). Among them, 632 (1.2%) had an elevated CK value. A re-screen at a mean age of 14 days (SD 8 days) revealed 14 subjects with persistent hyperCKemia, and DMD was confirmed in 3 of them. The incidence of DMD in Taiwan was 1:8,710 (95% CI 1 in 2,963 to 1 in 25,610) live birth males. Results of DMD DBS also assisted in Pompe newborn screening. CONCLUSIONS: NBS for DMD enables earlier management of the disease. The high re-screening rate could potentially be waived by moving the DBS WES assay to a second-tier test. The long-term benefit and the impact of newborn screening on the prognosis of DMD, however, remain further elucidated.

11.
BMC Genomics ; 23(1): 353, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525948

RESUMO

BACKGROUND: The cotton leafworm, Spodoptera littoralis, is a highly polyphagous pest of many cultivated plants and crops in Africa and Europe. The genome of this pest will help us to further understand the molecular mechanisms of polyphagy. RESULTS: Herein, the high-quality genome of S. littoralis was obtained by Pacific Bioscience (PacBio) sequencing. The assembled genome size of S. littoralis is 436.55 Mb with a scaffold N50 of 6.09 Mb, consisting of 17,207 annotated protein-coding genes. Phylogenetic analysis shows that S. littoralis and its sibling species S. litura diverged about 5.44 million years ago. Expanded gene families were mainly involved in metabolic detoxification and tolerance to toxic xenobiotics based on GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Comparative genomics analysis showed that gene families involved in detoxification and chemosensation were significantly expanded in S. littoralis, representing genetic characteristics related to polyphagy and an extensive host range. CONCLUSIONS: We assembled and annotated the reference genome of S. littoralis, and revealed that this pest has the genetic features of strong detoxification capacity, consistent with it being a significant risk to a wide range of host crops. These data resources will provide support for risk assessment and early warning monitoring of major polyphagous agricultural pests.


Assuntos
Genoma , Genômica , Animais , Gossypium/genética , Larva/genética , Filogenia , Spodoptera/genética
12.
J Clin Transl Hepatol ; 10(2): 247-253, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35528978

RESUMO

Background and Aims: Chronic hepatitis B virus (HBV) infection is a serious health problem worldwide. Evaluating liver injury in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) with detectable HBV DNA and normal alanine aminotransferase (ALT) is crucial to guide their clinical management. We aimed to investigate the stages of liver inflammation and fibrosis as well as the predictive accuracy of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in these patients. Methods: A total of 184 treatment-naïve HBeAg-negative CHB patients with detectable HBV DNA and normal ALT were enrolled. The Scheuer scoring system was used to classify liver inflammation and fibrosis. Results: The distribution of patients with different liver inflammation grades were as follows: G0, 0 (0%); G1, 97 (52.7%); G2, 68 (37.0%); G3, 12 (6.5%); and G4, 7 (3.8%). The distribution of patients with different liver fibrosis stages were as follows: S0, 22 (12.0%); S1, 72 (39.1%); S2, 42 (22.8%); S3, 19 (10.3%); and S4, 29 (15.8%). The areas under the receiver operating characteristic (AUROC) curves of GPR in predicting significant inflammation, severe inflammation, and advanced inflammation were 0.723, 0.895, and 0.952, respectively. The accuracy of GPR was significantly superior to that of ALT in predicting liver inflammation. The AUROCs of GPR in predicting significant fibrosis, severe fibrosis, and cirrhosis were 0.691, 0.780, and 0.803, respectively. The predictive accuracy of GPR was significantly higher than that of aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) in identifying advanced fibrosis and cirrhosis, and it was superior to FIB-4 but comparable to APRI in identifying significant fibrosis. Conclusions: Nearly half of the HBeAg-negative CHB patients with detectable HBV DNA and normal ALT levels had significant liver inflammation or fibrosis. GPR can serve as an accurate predictor of liver inflammation and fibrosis in these patients.

13.
Proc Natl Acad Sci U S A ; 119(20): e2101186119, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35533276

RESUMO

SignificanceFire is an increasing climate-driven threat to humans. While human demography can strongly modulate fire ignition rates or fire suppression, changes in CO2 released by fires feed back to climate. We show that human demography could reduce future fire activity, which would in turn attenuate global warming via an enhanced land carbon sink. This mitigation is strongest in a low-CO2-emission world, corresponding to ∼5 to 10 y of global CO2 emissions at today's levels by 2100. We highlight the strong role of human demography in global fire reduction and the potential for climate change mitigation by enhanced land carbon sequestration. We also note possible trade-offs, including loss of biodiversity in fire-dependent ecosystems and increases in severe fire events.


Assuntos
Incêndios , Aquecimento Global , Carbono , Dióxido de Carbono , Mudança Climática , Demografia , Ecossistema , Humanos
14.
Front Physiol ; 13: 858869, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600307

RESUMO

Objective: Metabolites in body fluids, such as lactate, glucose, and creatinine, have been measured by conventional methods to evaluate physical function and performance or athletic status. The objectives of the current study were to explore the novel metabolite biomarkers in professional swimmers with different competition levels using nuclear magnetic resonance (NMR) metabolomics, and try to establish a model to identify the athletic status or predict the competitive potential. Methods: Serum samples were collected from 103 elite and 84 sub-elite level Chinese professional swimmers, and were profiled by NMR analysis. Results: Out of the thirty-six serum metabolites profiled, ten were associated with the athletic status of swimmers (with p < 0.05). When compared with sub-elite swimmers, elite swimmers had higher levels of high-density lipoprotein (HDL), unsaturated fatty acid, lactic acid, and methanol. Elite swimmers had lower levels of isoleucine, 3-hydroxybutyric acid, acetoacetate, glutamine, glycine, and α-glucose. A model with four metabolites, including HDL, glutamine, methanol, and α-glucose, was established to predict athletic status by adjusting with different covariates. The area under the curve (AUC) of the best model was 0.904 (95% CI: 0.862-0.947), with a sensitivity and specificity of 75.5 and 90.2%, respectively. Conclusion: We have identified ten metabolite biomarkers with differentially expressed levels between elite and sub-elite swimmers, the differences could result from genetic or sports level between the two cohorts. A model with four metabolites has successfully differentiated professional swimmers with different competitive levels.

15.
Plant J ; 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35395128

RESUMO

Fruit ripening is a complex developmental process, which is modulated by both transcriptional and post-translational events. Control of fruit ripening is important in maintaining moderate quality traits and minimizing postharvest deterioration. In this study, we discovered that the transcription factor MaMYB4 acts as a negative regulator of fruit ripening in banana. The protein levels of MaMYB4 decreased gradually with banana fruit ripening, paralleling ethylene production, and decline in firmness. DNA affinity purification sequencing combined with RNA-sequencing analyses showed that MaMYB4 preferentially binds to the promoters of various ripening-associated genes including ethylene biosynthetic and cell wall modifying genes. Furthermore, ectopic expression of MaMYB4 in tomato delayed tomato fruit ripening, which was accompanied by downregulation of ethylene biosynthetic and cell wall modifying genes. Importantly, two RING finger E3 ligases MaBRG2/3, whose protein accumulation increased progressively with fruit ripening, were found to interact with and ubiquitinate MaMYB4, contributing to decreased accumulation of MaMYB4 during fruit ripening. Transient overexpression of MaMYB4 and MaBRG2/3 in banana fruit ripening delayed or promoted fruit ripening by inhibiting or stimulating ethylene biosynthesis, respectively. Taken together, we demonstrate that MaMYB4 negatively modulates banana fruit ripening, and that MaMYB4 abundance could be regulated by protein ubiquitination, thus providing insights into the role of MaMYB4 in controlling fruit ripening at both transcriptional and post-translational levels.

16.
Cancer Res ; 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35472075

RESUMO

Identifying colorectal cancer patient populations responsive to chemotherapy or chemoradiation therapy before surgery remains a challenge. Recently validated mouse protocols for organoid irradiation employ the single hit multi-target (SHMT) algorithm, which yields a single value, the D0, as a measure of inherent tissue radiosensitivity. Here we translate these protocols to human tissue to evaluate radioresponsiveness of patient-derived organoids (PDOs) generated from normal human intestines and rectal tumors of patients undergoing neoadjuvant therapy. While PDOs from adenomas with a logarithmically-expanded Lgr5+-intestinal stem cell population retain the radioresistant phenotype of normal colorectal PDOs, malignant transformation yields PDOs from a large patient subpopulation displaying marked radiosensitivity due to reduced homologous recombination-mediated DNA repair. A proof-of-principle pilot clinical trial demonstrated that rectal cancer patient responses to neoadjuvant chemoradiation, including complete response, correlate closely with their PDO D0 values. Overall, upon transformation to colorectal adenocarcinoma, broad radiation sensitivity occurs in a large subset of patients that can be identified using SHMT analysis of PDO radiation responses.

17.
Tzu Chi Med J ; 34(2): 219-225, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35465280

RESUMO

Objectives: Transarterial chemoembolization (TACE) or sorafenib may prolong survival in patients with unresectable hepatocellular carcinoma (HCC); however, whether their combination prolongs survival than TACE alone remains controversial. We aimed to compare the overall survival (OS) of patients with unresectable HCC treated with TACE plus sorafenib (TACE-S) versus TACE alone. Materials and Methods: All patients with unresectable HCC who received TACE as the initial therapy between January 2006 and January 2017 at Taipei Tzu Chi Hospital were enrolled. We matched patients treated with TACE-S and those treated with TACE alone (TACE) by performing propensity score matching at a 1:2 ratio. Our primary outcome was OS during a 10-year follow-up period, and represented as a hazard ratio calculated using Cox proportional hazard regression models. Results: Among 515 patients with unresectable HCC were treated initially with TACE, 56 receiving TACE-S group and 112 receiving TACE alone (TACE group) were included in the primary outcome analysis. The TACE-S group had significantly longer median OS than did the TACE group (1.55 vs. 0.32, years; P < 0.001), and the 5-year OS rates was 10.7% in the TACE-S group and 0.9% in the TACE group (P < 0.001). In multivariate analyses, patients with a lower Child-Pugh score, tumor size ≤5 cm, and no extrahepatic metastasis before treatment and those receiving antiviral agents and receiving TACE-S had longer OS (all P < 0.001). Conclusion: Antiviral agents and the combination of TACE with sorafenib may improve the OS of patients with unresectable HCC.

18.
Nutrients ; 14(8)2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35458099

RESUMO

Vitamin D has been implicated in the pathogenesis of skeletal disorders and various autoimmune disorders. Vitamin D can be consumed from the diet or synthesized in the skin upon ultraviolet exposure and hydroxylation in the liver and kidneys. In its bioactive form, vitamin D exerts a potent immunomodulatory effect and is important for bone health. Juvenile idiopathic arthritis (JIA) is a collection of inflammatory joint diseases in children that share the manifestation of inflamed synovium, which can result in growth arrest, articular deformity, bone density loss, and disability. To evaluate the potential effect of vitamin D on JIA disease manifestations and outcomes, we review the role of vitamin D in bone metabolism, discuss the mechanism of vitamin D in modulating the innate and adaptive immune systems, evaluate the clinical significance of vitamin D in patients with JIA, and summarize the supplementation studies.


Assuntos
Artrite Juvenil , Doenças Ósseas Metabólicas , Deficiência de Vitamina D , Artrite Juvenil/tratamento farmacológico , Densidade Óssea , Criança , Suplementos Nutricionais , Humanos , Vitamina D/metabolismo , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas
19.
Front Psychol ; 13: 817639, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401312

RESUMO

Aim: We aim to explore the impact of occupational stress on the quality of life of nurses in infectious disease departments and to explore the mediating role of psychological resilience on this impact. Background: Sudden public health events and the prevalence of infectious diseases give nurses in infectious disease departments a heavy task load and high occupational stress, which can affect their quality of life, and which is closely related to the quality of clinical care they provide. There are few existing studies on occupational stress, psychological resilience, and the quality of life of nurses in infectious disease departments. Methods: We collected data from infectious-disease-specialized hospitals or infectious disease departments of general hospitals in China. In total 1,536 nurses completed questionnaires: the Effort-Reward Imbalance Questionnaire, the Connor-Davidson Resilience Scale, and the World Health Organization Quality of Life Brief Scale. We use a structural equation model to test the mediating role of the psychological resilience in the relationship between occupational stress and quality of life. Results: Among 1,536 participants, 88.2% experienced an effort-reward imbalance. The average scores for psychological resilience and quality of life were 56.06 (SD = 14.19) and 51.80 (SD = 8.23), respectively. Our results show that occupational stress is negatively correlated with psychological resilience (r = -0.28, p < 0.01) and quality of life (r = -0.44, p < 0.01). In addition, we find that psychological resilience is positively correlated with quality of life (r = 0.55, p < 0.01) and that the indirect effect of occupational stress on quality of life through psychological resilience is significant (ß = -0.036, 95% CI: 0.027 to 0.426), indicating at least a partial mediating role of psychological resilience. Conclusion: A high proportion of nurses in infectious disease departments felt that their jobs' effort-reward imbalance was high. These nurses' scores for psychological resilience were in the middle level among Chinese people generally, but their quality of life was lower than the Chinese norm. We conclude that occupational stress has an important impact on their quality of life, and psychological resilience plays a partial mediating role on this impact. Implications for Nursing Management: Hospital managers can benefit from paying attention to the occupational stress of nurses and helping to improve the quality of life of nurses by alleviating this occupational stress and improving psychological resilience.

20.
Int J Mol Sci ; 23(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35409204

RESUMO

Mirogabalin (MGB, Tarlige®), an inhibitor of the α2δ-1 subunit of voltage-gated Ca2+ (CaV) channels, is used as a way to alleviate peripheral neuropathic pain and diabetic neuropathy. However, to what extent MGB modifies the magnitude, gating, and/or hysteresis of various types of plasmalemmal ionic currents remains largely unexplored. In pituitary tumor (GH3) cells, we found that MGB was effective at suppressing the peak (transient, INa(T)) and sustained (late, INa(L)) components of the voltage-gated Na+ current (INa) in a concentration-dependent manner, with an effective IC50 of 19.5 and 7.3 µM, respectively, while the KD value calculated on the basis of minimum reaction scheme was 8.2 µM. The recovery of INa(T) inactivation slowed in the presence of MGB, although the overall current-voltage relation of INa(T) was unaltered; however, there was a leftward shift in the inactivation curve of the current. The magnitude of the window (INa(W)) or resurgent INa (INa(R)) evoked by the respective ascending or descending ramp pulse (Vramp) was reduced during cell exposure to MGB. MGB-induced attenuation in INa(W) or INa(R) was reversed by the further addition of tefluthrin, a pyrethroid insecticide known to stimulate INa. MGB also effectively lessened the strength of voltage-dependent hysteresis of persistent INa in response to the isosceles triangular Vramp. The cumulative inhibition of INa(T), evoked by pulse train stimulation, was enhanced in its presence. Taken together, in addition to the inhibition of CaV channels, the NaV channel attenuation produced by MGB might have an impact in its analgesic effects occurring in vivo.


Assuntos
Ácido Acético , Neoplasias Hipofisárias , Compostos Bicíclicos com Pontes , Humanos , Neoplasias Hipofisárias/patologia , Sódio
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