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1.
Pest Manag Sci ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34761501

RESUMO

BACKGROUND: Plant diseases caused by viruses and fungi have caused great losses to crop quality and yield. The discovery of novel and efficient antiviral and antiphytopathogenic-fungus agents is urgently needed. It is the most important pesticide innovation strategy to find active compounds from natural products. Here, glyantrypine-family alkaloids were taken as the parent structures and a series of their derivatives were designed through molecular splicing, ring expansion, and ring contraction strategies, and synthesized. The anti-tobacco mosaic virus (TMV) activities and antifungal activities of these alkaloids were systematically investigated for the first time. RESULT: The antiviral activities of compounds 7bb, 7bc, 11c, 18b, 18d, 28d, and 28e are equivalent to or better than that of ribavirin (inhibitory rates 39%, 37%, and 40% at 500 µg mL-1 for inactivation, curative, and protection activity in vivo, respectively). Compounds 18d and 28d with good antiviral activities were selected for antiviral mode of action studies, which indicated that these alkaloids could achieve good antiviral effects by inhibiting TMV particle extension during assembly. These compounds also exhibited broad-spectrum fungicidal activities. CONCLUSION: Glyantrypine-family alkaloids and their derivatives were synthesized and evaluated for anti-TMV and fungicidal activities for the first time. Compounds 18d and 28d with excellent antiviral activities and compound 7bc with remarkable fungicidal activity emerged as novel lead compounds. This study lays a foundation for the application of glyantrypine alkaloids in plant protection.

2.
Front Cell Infect Microbiol ; 11: 673503, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765565

RESUMO

Background: Over the last two decades, the prevalence of colistin resistance among the members of Enterobacteriaceae has been increasing, particularly among Klebsiella pneumoniae isolates; this limits the potential use of colistin and leads to worsened clinical outcomes. Methods: We investigated the prevalence and genetic characteristics of colistin-resistant K. pneumoniae (COLR-KP) in clinical isolates using genomic sequencing. Results: In total, 53 K. pneumoniae isolates (4.5%, 53/1,171) were confirmed as COLR-KP, of which eight isolates carried mobile colistin-resistant (mcr) gene. Although the overall prevalence rate (0.7%, 8/1,171) of mcr-like genes in clinical K. pneumoniae remained relatively low, the presence of mcr (15.1%, 8/53) among the COLR-KP isolates indicated that the mobile resistance gene was already widespread among K. pneumoniae isolates in hospital setting. We randomly selected 13 COLR-KP isolates (four mcr-bearing and nine non-mcr-bearing isolates) for whole-genome sequencing, including two pandrug-resistant and four sequence type 11 (ST11) isolates. Phylogenetic analysis revealed that all COLR-KP isolates were genetically diverse. Among the four mcr-bearing isolates, three (KP4, KP18, and KP30) were positive for mcr-1 and one (KP23) for mcr-8; none of the other mcr genes were detected. The mcr-1 in the KP4 and KP30 isolates were located in an IncX4 plasmid (approximately 33 kb) and could be successfully transferred to Escherichia coli J53AZR. In contrast, for the mcr-8-bearing plasmid in KP23 (IncFII), colistin resistance could not be transferred by conjugation. The mcr-1-producing isolate KP18 coexists a novel plasmid-carried tigecycline resistance gene tmexCD1-toprJ1. The most common chromosomal mutation associated with colistin resistance was a T246A amino acid substitution in PmrB, which was identified in most COLR-KP isolates (11/13, 84.6%). All ST11 isolates additionally had an R256G amino acid substitution. Critical virulence factors associated with hypervirulent K. pneumoniae were detected in four COLR-KP isolates; these virulence factors included aerobactin, salmochelin, and yersiniabactin. Conclusion: We found that mcr-bearing COLR-KP emerged in our hospital and was growing at an increasing rate. Simultaneous emergence of hypervirulence and colistin-tigecycline-carbapenem resistance in the epidemic clone ST11 K. pneumoniae was also observed; this highlights the significance of active and continuous surveillance.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Hospitais de Ensino , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Filogenia , Plasmídeos , Atenção Terciária à Saúde
3.
Acta Diabetol ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34761326

RESUMO

AIMS: Dysglycemia, including the three domains hyperglycemia, hypoglycemia, and increased glycemic variability (GV), is associated with high mortality among critically ill patients. However, this association differs by diabetes status, and reports in this regard are limited. This study aimed to evaluate the associations between the three dysglycemia domains and mortality in critically ill patients by diabetes status and determined the contributing factors for dysglycemia. METHODS: This retrospective study included 958 critically ill patients (admitted to the ICU) with or without DM. Dysglycemia was defined as abnormality of any of the three dimensions. We evaluated the effects of the three domains of glucose control on mortality using binary logistic regression and then adjusted for confounders. The associations between dysglycemia and other variables were investigated using cumulative logistic regression analysis. RESULT: GV independently and similarly affected mortality in both groups after adjustment for confounders (DM: odds ratio [OR], 1.05; 95% confidence interval [CI]: 1.03-1.08; p <0.001; non-DM: OR, 1.07; 95% CI, 1.03-1.11; p = 0.002). Hypoglycemia was strongly associated with ICU mortality among patients without DM (3.12; 1.76-5.53; p <0.001) and less so among those with DM (1.18; 0.49-2.83; p = 0.72). Hyperglycemia was non-significantly associated with mortality in both groups. However, the effects of dysglycemia seemed cumulative. The factors contributing to dysglycemia included disease severity, insulin treatment, glucocorticoid use, serum albumin level, total parenteral nutrition, duration of diabetes, elevated procalcitonin level, and need for mechanical ventilation and renal replacement therapy. CONCLUSION: The association between the three dimensions of dysglycemia and mortality varied by diabetes status. Dysglycemia in critical patients is associated with excess mortality; however, glucose management in patients should be specific to the patient's need considering the diabetes status and broader dimensions. The identified factors for dysglycemia could be used for risk assessment in glucose management requirement in critically ill patients, which may improve clinical outcomes.

4.
ACS Med Chem Lett ; 12(11): 1838-1844, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34745429

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has stimulated the search for effective drugs for its prevention and treatment. Natural products are an important source for new drug discovery. Here, we report that, NK007(S,R), a tylophorine malate, displays high antiviral activity against SARS-CoV-2 with an EC50 0.03 µM in vitro, which is substantially lower than that of remdesivir (EC50: 0.8 µM in vitro), the only authorized drug to date. The histopathological research revealed that NK007(S,R) (5 mg/kg/dose) displayed a protection effect in lung injury induced by SARS-CoV-2, which is better than remdesivir (25 mg/kg/dose). We also prepared two nanosized preparations of NK007(S,R), which also showed good efficacy (EC50: NP-NK007, 0.007 µM in vitro; LP-NK007, 0.014 µM in vitro). Our findings suggest that tylophora alkaloids, isolated from the traditional Chinese medicine Cynanchum komarovii AL, offer a new skeleton for the development of anticoronavirus drug candidate.

5.
Int J Nurs Stud ; 125: 104110, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34736073

RESUMO

BACKGROUND: Mild cognitive impairment affects 36% of people aged ≥65 years in China, around 50% of whom will develop dementia within 3 years. Early intervention can slow disease progression and delay the onset of dementia; however, whether a multicomponent intervention can decelerate the progression of mild cognitive impairment remains unknown. OBJECTIVE: To evaluate the effects of a multicomponent intervention to slow mild cognitive impairment progression in Chinese patients. DESIGN: Randomized controlled trial. SETTING(S) AND PARTICIPANTS: This study was conducted in two large regional communities in Guangzhou, China. Patients aged ≥ 65 years diagnosed with mild cognitive impairment were included. METHODS: A total of 112 eligible participants were assigned to receive either a 6-month multicomponent intervention or usual care from September 2019 until January 2021. Data were collected at the beginning of the study and at 1, 3, and 6 months thereafter. The primary outcomes were cognitive function, comprehensive physical capacity, depression, and quality of life. Analysis followed the intention-to-treat principle. A generalized estimating equation was used to determine intervention effects. RESULTS: At baseline, clinical characteristics did not differ significantly between groups. Significant interaction effects between time and group were detected (p < 0.001), indicating that the scores of five outcomes (cognitive function, short physical performance battery, timed up and go test, quality of life, and depression) of intervention and control groups changed differently over time. Participants in the intervention group were found to have a significantly greater improvement in cognitive function, physical function, quality of life, and fewer depression symptoms compared with the control group at baseline and follow-up periods. CONCLUSIONS: This study demonstrates the beneficial effects of a multicomponent intervention on cognitive function, physical function, depression symptoms, and quality of life in people with mild cognitive impairment in the East Asia region. The effectiveness and feasibility of this intervention program suggest that its application should be promoted in community settings to delay the progression of disease in people with mild cognitive impairment. Registration number:ChiCTR1900026042 Tweetable abstract: The multicomponent intervention improves cognitive/physical function, depression, and quality of life, slowing cognitive impairment progression.

6.
Front Nutr ; 8: 738550, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708064

RESUMO

Background: Malnutrition is common in patients with cancer and is associated with adverse outcomes, but few data exist in elderly patients. The aim of this study was to report the prevalence of malnutrition using three different scoring systems and to examine the possible clinical relationship and prognostic consequence of malnutrition in elderly patients with cancer. Methods: Nutritional status was assessed by using controlling nutritional status (CONUT), the prognostic nutritional index (PNI), and the nutritional risk index (NRI). Quality-of-life (Qol) was assessed during admission by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30. Performance status (PS) was assessed by using the Eastern Cooperative Oncology Group (ECOG) classification. The relationship between nutritional status and overall survival and Qol were examined. Results: Data were available for 1,494 elderly patients with cancer (63.65% male), the mean age was 70.76 years. According to the CONUT, NRI, and PNI, 55.02, 58.70, and 11.65% patients were diagnosed with malnutrition, respectively. Worse nutritional status was related to older, lower BMI, lower hand grip strength, and more advanced tumor stage. All malnutrition indexes were correlated with each other (CONUT vs. PNI, r = -0.657; CONUT vs. NRI scores, r = -0.672; PNI vs. NRI scores, r = 0.716, all P < 0.001). During a median follow-up of 43.1 months, 692 (46.32%) patients died. For patients malnourished, the incidence rate (events-per-1,000person-years) was as follows: CONUT (254.18), PNI (429.91), and NRI (261.87). Malnutrition was associated with increased risk for all-cause mortality (adjust HR [95%CI] for CONUT: 1.09 [1.05-1.13], P < 0.001; PNI: 0.98[0.97-0.99], P < 0.001; NRI: 0.98 [0.98-0.99], P < 0.001). All malnutrition indexes improved the predictive ability of the TNM classification system for all-cause mortality. Deterioration of nutritional status was associated with deterioration in Qol parameters and immunotherapeutic response (P < 0.001). Conclusions: Malnutrition was prevalent in elderly patients with cancer, regardless of the assessment tools used, and associated with lower Qol and the immunotherapy response.

8.
Front Neurosci ; 15: 726505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671239

RESUMO

Background: Menstrual migraine without aura (MMoA) refers to a specific type of migraine that is associated with the female ovarian cycle. It is particularly serious and has brought huge life pressure and mental burden to female patients. Acupuncture has been commonly used to prevent migraines and relieve concomitant emotional disorders; however, the physiological mechanism underlying this intervention remains unclear. This study aimed to use resting-state functional magnetic resonance imaging (rsfMRI) to investigate whether acupuncture can modulate brain function and if the potential influence on brain activity correlates with improving emotional symptoms in MMoA patients. Methods: Overall, 44 patients were randomly divided into a true acupuncture (TA) group and the sham acupuncture (SA) group. Patients underwent rsfMRI before and after 3-month treatment, the amplitude of low-frequency fuctuations (ALFF) and regional homogeneity (ReHo) in rsfMRI were calculated. Zung self-rating anxiety scale (SAS), Zung self-rating depression scale (SDS), frequency of migraine attacks, visual analog scale, and intensity of the migraine were used for evaluate the clinical effect. The clinical changes of variables were also used to further assess the correlation with brain activity in MMoA patients. Results: After acupuncture treatment, the emotional symptoms of both groups of patients improved, and the clinical symptoms of migraine were alleviated. The major finding of our study was that patients with MMoA showed lower ALFF value in the left anterior cingulate and the value was positively correlated with the decreases in the SAS and SDS scores. In the SA group, common brain regions responded both in ALFF and regional homogeneity values mainly in the insula, and no significant correlations were observed between brain regions and clinical variables. Conclusions: These results indicated that both two acupuncture treatments were helpful in treating migraine and could improve emotion symptoms. TA had a relatively better effect in reducing the frequency of migraine attack than SA. The two therapies have different modulation effects as TA regulates emotional disorders by modulating the frontal-limbic regions, and SA may modulate pain perception through the placebo effect on insula and by indirectly regulating emotional disorders. These findings provided evidence that acupuncture is a complementary and alternative therapy to relieve clinical symptoms in female patients with migraines and could help enhance clinical diagnosis and treatment. Clinical Trial Registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR-IOR-15006648. Registered 23 June 2015].

9.
Food Res Int ; 149: 110678, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34600680

RESUMO

Sunflower pollen is a natural nutritious food with a long history and multiple functions, however, the main chemical components apart from flavonoids and their biosynthesis processes have not been thoroughly investigated. In this study, seven hydroxycinnamic acid amides (HCAAs) (1-7) abundant in sunflower pollen were isolated and identified as one type of the pollen's main chemicals. For a comprehensive understanding of HCAA biosynthesis in Helianthus annuus flowers, RNA-seq, metabolomics, and key genes related to biosynthesis in the sunflower were studied. A large number of compounds at different sunflower growth stages (the 7th, 14th, 21st, and 28th days) and high expression levels of related genes in the transcriptome were detected. A molecular network was constructed to clarify the synthetic pathway of HCAAs, which revealed high transcriptional levels of spermidine hydroxycinnamoyl transferase genes (HaSHT2795 and HaSHT2436) in 14-21-days-old flowers. HaSHT2795 enzymes catalyze tri-coumaroylspermidine formation, and virus-induced gene silencing to inhibit HaSHT2795 and HaSHT2436 could significantly reduce the synthesis of hydroxycinnamic acid amides in sunflower pollen. HCAAs were inferred to be related to the formation of pollen walls and the health effects of pollen. Analyzing HCAA biosynthesis and accumulation in H. annuus pollen will be helpful to understand the functions of HCAAs in the development of pollen and its nutritional value.


Assuntos
Ácidos Cumáricos , Helianthus , Amidas , Helianthus/genética , Pólen/genética , Transcriptoma
10.
Front Genet ; 12: 728333, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539754

RESUMO

Cerebral ischemic stroke (IS) is a complex disease caused by multiple factors including vascular risk factors, genetic factors, and environment factors, which accentuates the difficulty in discovering corresponding disease-related genes. Identifying the genes associated with IS is critical for understanding the biological mechanism of IS, which would be significantly beneficial to the diagnosis and clinical treatment of cerebral IS. However, existing methods to predict IS-related genes are mainly based on the hypothesis of guilt-by-association (GBA). These methods cannot capture the global structure information of the whole protein-protein interaction (PPI) network. Inspired by the success of network representation learning (NRL) in the field of network analysis, we apply NRL to the discovery of disease-related genes and launch the framework to identify the disease-related genes of cerebral IS. The utilized framework contains three main parts: capturing the topological information of the PPI network with NRL, denoising the gene feature with the participation of a stacked autoencoder (SAE), and optimizing a support vector machine (SVM) classifier to identify IS-related genes. Superior to the existing methods on IS-related gene prediction, our framework presents more accurate results. The case study also shows that the proposed method can identify IS-related genes.

11.
Chem Commun (Camb) ; 57(72): 9140-9143, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498639

RESUMO

The hydrosulfamoylation of diverse aryl olefins provides facile access to alkylsulfonamides. Here we report a novel protocol utilizing radical-mediated addition and a thiol-assisted strategy to achieve the hydrosulfamoylation of diverse styrenes in modest to excellent yields under mild and economic reaction conditions. The methodology was found to provide an efficient and convenient approach for the synthesis of the anti-migraine drug naratriptan and it also can be used for the late-stage functionalization of natural products or medicines.


Assuntos
Piperidinas/síntese química , Estirenos/química , Sulfonas/química , Triptaminas/síntese química , Catálise , Estrutura Molecular , Oxirredução , Processos Fotoquímicos , Piperidinas/química , Triptaminas/química
12.
Mitochondrial DNA B Resour ; 6(9): 2565-2566, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377830

RESUMO

We describe the mitochondrial genome sequence of a torrent frog, Amolops jinjiangensis. The mitogenome was extracted and assembled for the first time by restriction site-associated DNA sequencing (RAD-seq). The total length is 17,780 bp, containing 13 protein-coding genes (PCGs), two ribosomal RNA genes, 22 transfer RNA genes, and one control region. The gene rearrangement was detected as the W-OL-ANCY gene cluster which consisted with several published Amolops mitogenomes. The phylogenetic tree was constructed based on 13 protein-coding genes of A. jinjiangensis and 11 closely related species by Bayesian analyses.

13.
J Healthc Eng ; 2021: 2178281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413966

RESUMO

Background: Ferroptosis is a type of cell death with major topic of debate under current research and plays an important role in disease regulation. Objective: In this study, the literature management software Bibexcel and knowledge graph tool VOSviewer were used to summarize and analyze the international research trends and hotspots about ferroptosis in recent years, which highlight the disease mechanism, diagnosis, and treatment related to ferroptosis. Material/Methods. The core collection database of Web of Science was used for retrieving ferroptosis research literature. The information such as the amount of text, the country, the period, the institution, the fund, and the keywords was extracted by the bibliometric tool Bibexcel. The cooccurrence and clustering function of VOSviewer were used to analyze the high-frequency keywords and the cooperative network of the author, institution, and country. Results: The research of ferroptosis started late and was formally proposed in 2012. It has developed rapidly and presented an "exponential" growth trend. China, the United States, Germany, Japan, and France are the main national forces of ferroptosis research development. The United States and China have a relatively high degree of support and attention to ferroptosis. Exploring oxidative stress, inducers/inhibitors, synergistic antitumor effect, relationships with other cell death types, GSH/GPX4 and iron metabolism imbalance related mechanisms of ferroptosis, and ferroptosis in the nervous system disease, ischemia-reperfusion injury, tumor, inflammation, and age-related diseases are the hot research directions. Conclusion: Ferroptosis has been a research hotspot in the field of biomedicine in recent years and has attracted the attention of scholars all over the world. The occurrence mechanism of ferroptosis and its application in neurological diseases, ischemia and reperfusion injury, tumors, inflammation, and aging are the hot directions of current research. In the future, ferroptosis can be appropriately considered for strengthening new approaches, new diseases, new inductors, new inhibitors, clinical transformation, and traditional medicine research.


Assuntos
Ferroptose , Doenças do Sistema Nervoso , Bibliometria , Bases de Dados Factuais , Humanos , Publicações , Estados Unidos
14.
Front Psychol ; 12: 666765, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34385952

RESUMO

Extant research has investigated the relationship between work engagement and various outcomes, such as job performance and organizational commitment, neglecting the effect of work engagement on social relationships at work. Drawing upon person-environment fit theory and LMX theory, the present study aims to examine the effect of (in)congruence between leader and follower work engagement on leader-member exchange (LMX) and the moderating effect of conscientiousness. About 273 employees and 72 leaders participated in this study and completed the measurements of work engagement, conscientiousness, and LMX at two time points. Using cross-level polynomial regressions, we found that, compared with incongruent work engagement, employees perceived high levels of LMX quality when their work engagement was aligned with that of their leaders. Regarding the congruence, the employees reported higher levels of LMX when congruence in work engagement was at higher rather than lower levels. Regarding the incongruence, when the employees engaged less in their work tasks than their leaders, they were more likely to experience lower LMX. Moreover, the negative relationship between incongruence in leader and follower work engagement and LMX was mitigated when followers were more conscientious. All our hypotheses were supported. Both theoretical and practical implications for work engagement as well as future directions are discussed.

15.
J Agric Food Chem ; 69(34): 9754-9763, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34415761

RESUMO

Plant viruses and fungi are a serious threat to food security and natural ecosystems. The efficient and environment-friendly control methods are urgently needed to help safeguard such resources. Here, we achieved the efficient synthesis of toad alkaloid dehydrobufotenine in eight steps with an overall yield of 8% from 5-methoxyindole. A series of dehydrobufotenine derivatives were designed, synthesized, and evaluated for their antiviral and fungicidal activities systematically. It was found for the first time that these compounds have good anti-plant virus activities and anti-plant pathogen activities. The antiviral activities of 21 compounds were similar to or better than those of ribavirin. Compounds 12 and 17 displayed better antiviral activities than ningnanmycin which is perhaps the most effective anti-plant virus agent. The antiviral mechanism research study of 12 revealed that it could make 20S CP disk fusion and aggregation. Further molecular docking results showed that there are hydrogen bonds between compounds 12, 17, and tobacco mosaic virus CP. The docking results are consistent with the antiviral activity. These compounds also displayed broad-spectrum fungicidal activities against 14 kinds of fungi, especially for Sclerotinia sclerotiorum. In this work, the synthesis, structure optimization, structure-activity relationship studies, and mode of action research of dehydrobufotenine alkaloids were carried out. It provides a reference for the development of the anti-plant virus agent and anti-plant pathogen agent from toad alkaloids.


Assuntos
Alcaloides , Fungicidas Industriais , Praguicidas , Vírus de Plantas , Vírus do Mosaico do Tabaco , Alcaloides/farmacologia , Antivirais/farmacologia , Ascomicetos , Desenho de Fármacos , Ecossistema , Fungos , Fungicidas Industriais/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
16.
Redox Biol ; 46: 102082, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34343908

RESUMO

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of extracellular matrix in the lung with fibroblast-to-myofibroblast transition, leading to chronically compromising lung function and death. However, very little is known about the metabolic alterations of fibroblasts in IPF, and there is still a lack of pharmaceutical agents to target the metabolic dysregulation. Here we show a glycolysis upregulation and fatty acid oxidation (FAO) downregulation in fibroblasts from fibrotic lung, and perturbation of glycolysis and FAO affects fibroblasts transdifferentiation. In addition, there is a significant accumulation of succinate both in fibrotic lung tissues and myofibroblasts, where succinate dehydrogenase (SDH) operates in reverse by reducing fumarate to succinate. Then succinate contributes to glycolysis upregulation and FAO downregulation by stabilizing HIF-1α, which promotes the development of lung fibrosis. In addition, we identify a near-infrared small molecule dye, IR-780, as a targeting agent which stimulates mild inhibition of succinate dehydrogenase subunit A (SDHA) in fibroblasts, and which inhibits TGF-ß1 induced SDH and succinate elevation, then to prevent fibrosis formation and respiratory dysfunction. Further, enhanced cell retention of IR-780 is shown to promote severe inhibition of SDHA in myofibroblasts, which may contribute to excessive ROS generation and selectively induces myofibroblasts to apoptosis, and then therapeutically improves established lung fibrosis in vivo. These findings indicate that targeting metabolic dysregulation has significant implications for therapies aimed at lung fibrosis and succinate dehydrogenase is an exciting new therapeutic target to treat IPF.


Assuntos
Fibrose Pulmonar Idiopática , Preparações Farmacêuticas , Bleomicina/toxicidade , Fibroblastos , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/genética , Pulmão , Miofibroblastos , Succinato Desidrogenase/genética
17.
Asia Pac J Clin Nutr ; 30(2): 206-212, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34191422

RESUMO

BACKGROUND AND OBJECTIVES: To investigate the effects of oral preoperative regimens on gastric emptying time in relation to BMI in Chinese adults. METHODS AND STUDY DESIGN: The enrolled 56 adults were divided into three groups (normal-weight, underweight, and overweight) and completed a regimen of two drinks after a 2-week interval. After drinking a carbohydrate regimen (CD, 50 g carbohydrates) or a carbohydrate glutamine regimen (CGD, 44 g carbohydrates and 6 g glutamine) labelled with 99mTc-DTPA (99mTc-diethylenetriaminepentaacetic acid), gastric emptying times T50 and T90 were measured using a curve derived from scintigraphic images. RESULTS: T50 and T90 had no significant difference between the CD and CGD regimens. T50 was significantly delayed in the underweight participants (BMI <18.5 kg/m2, as Chronic Energy Deficiency, CED) compared with the normal-weight participants after drinking CD (p=0.003) or CGD (p=0.002), as well as T90 after CD (p=0.019). There was no difference in glucose concentrations between the three groups. There are negative correlations between body weight and gastric emptying time T50 (r=-0.461, p=0.016) or T90 (r=-0.553, p=0. 003) after drinking CD, as well as T50 (r=-0.553, p=0.003) after drinking CGD. CONCLUSIONS: Underweight adults should be careful to take oral preoperative regimens 2 hours before surgery and consider reducing the volume because of a slower gastric emptying rate.


Assuntos
Esvaziamento Gástrico , Adulto , China , Estudos Cross-Over , Humanos
18.
Pest Manag Sci ; 77(10): 4691-4700, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34132452

RESUMO

BACKGROUND: Plant diseases have been gripping agricultural production, seriously affecting the growth and yields of crops. Marine natural products are an important source for novel drugs discovery. In this work, pityriacitrin marine alkaloids were selected as the parent structures. A series of pityriacitrin alkaloid analogues were rationally designed, synthesized and evaluated for their antiviral activities and fungicidal activities. RESULT: Most of these compounds were demonstrated to have higher antiviral activities than ribavirin. Particularly, compounds 3a, 3e, 8f, 8g, and 9g displayed higher anti-TMV activities than ningnanmycin at 500 µg·mL-1 . Mechanism research revealed that 3a could bind to TMV CP with an excellent affinity (Ka  = 8.67 × 106 L·mol-1 ), thus interfere with the assembly of virus particles. These alkaloids also showed broad-spectrum fungicidal activities against eight kinds of phytopathogenic fungi. Compound 5f with 1.43-3.84 µg·mL-1 EC50 value against three fungi emerged as a new fungicidal candidate. CONCLUSION: Pityriacitrin alkaloids and their derivatives were synthesized and evaluated for anti-TMV and fungicidal activities for the first time. Compounds 3a and 5f with excellent activities emerged as new candidates for antiviral research and fungicidal research, respectively. Current work provided a new idea for the molecular design and development of novel plant virus and fungi inhibitors in the future. © 2021 Society of Chemical Industry.


Assuntos
Alcaloides , Vírus do Mosaico do Tabaco , Alcaloides/farmacologia , Antivirais/farmacologia , Desenho de Fármacos , Fungos , Alcaloides Indólicos , Relação Estrutura-Atividade
19.
Front Genet ; 12: 669441, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093660

RESUMO

Human height is a polygenic trait, influenced by a large number of genomic loci. In the pre-genomic era, height prediction was based largely on parental height. More recent predictions of human height have made great strides by integrating genotypic data from large biobanks with improved statistical techniques. Nevertheless, recent studies have not leveraged parental height, an added feature that we hypothesized would offer complementary predictive value. In this study, we assessed the predictive power of polygenic risk scores (PRS) combined with the traditional parental height predictors. Our study analyzed genotypic data and parental height from 1,071 trios from the United Kingdom Biobank and 444 trios from the Framingham Heart Study. We explored a series of statistical models to fully evaluate the performance of several PRS constructed together with parental information and proposed a model we call PRS++ that includes gender, parental height, and PRSs of parents and proband. Our estimate of height with an R 2 of ∼0.82 is, to our knowledge, the most accurate estimate yet achieved for predicting human adult height. Without parental information, the R 2 from the best PRS-driven model is ∼0.73. In summary, using adult height prediction as an example, we demonstrated that traditional predictors still play important roles and merit integration into the current trends of intensive PRS approaches.

20.
Aging Cell ; 20(6): e13370, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33957702

RESUMO

Research on ageing-associated genes is important for investigating ageing and anti-ageing strategies. Here, we firstly reported that the human positive cofactor 4 (PC4), a multifunctional and highly conserved nucleoprotein, is accumulated and activated during ageing and causes global accelerated ageing process by disrupting proteostasis. Mechanistically, PC4 interacts with Sin3-HDAC complex and inhibits its deacetylated activity, leads to hyper-acetylation of the histones at the promoters of mTOR-related genes and causes mTOR signalling activation. Accordingly, mTOR activation causes excessive protein synthesis, resulting in impaired proteostasis and accelerated senescence. These results reveal a new biological function of PC4 in vivo, recognizes PC4 as a new ageing-associated gene and provides a genetically engineered mouse model to simulate natural ageing. More importantly, our findings also indicate that PC4 is involved in histone acetylation and serves as a potential target to improve proteostasis and delay ageing.

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