Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.666
Filtrar
1.
Adv Wound Care (New Rochelle) ; 12(1): 1-14, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35081741

RESUMO

Objective: Although the use of dexamethasone as an adjunct agent is associated with alleviating pain and prolonging analgesic duration in local wound infiltration (LWI), efficacy and safety of dexamethasone infiltration have not been fully explored. The study sought to quantify the pooled effects of dexamethasone infiltration on postoperative pain, analgesic consumption, and side effects through a review of randomized controlled trials (RCTs). Approach: RCTs comparing dexamethasone + LWI with LWI alone were retrieved from seven electronic databases. Co-primary outcomes were rest pain scores and cumulative morphine equivalent consumption within 24 h postoperatively. The study followed PRISMA, AMSTAR, and the Cochrane Collaboration. Results: Eight trials comprising 609 patients were included in the final analysis. Results indicated that dexamethasone infiltration effects were only statistical but not clinically significant at individual time points of rest pain and patient satisfaction scores. Notably, the effect of dexamethasone infiltration therapy on other pain-related parameters, including cumulative morphine consumption (mean difference, -9.05 mg; 95% CI: -22.47 to 4.37), was not significantly different compared with the control group. Analysis showed no significant differences in safety indicators between the two groups. The overall quality of evidence was high to very low. Innovation: Although statistically significant effects of dexamethasone infiltration were observed for some outcomes of postoperative wound pain, the overall benefits were below the expected minimal clinically important difference. Conclusions: In summary, the current evidence does not support routine clinical use of dexamethasone in LWI. However, further studies should explore the clinical value of preemptive analgesia and safety of a combination of dexamethasone with ropivacaine for LWI.


Assuntos
Analgesia , Dor Pós-Operatória , Humanos , Ropivacaina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Morfina/farmacologia , Morfina/uso terapêutico , Analgesia/métodos , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
J Colloid Interface Sci ; 630(Pt A): 618-628, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36272216

RESUMO

The low energy density issue raises serious concerns for the large-scale application of supercapacitors. However, the development and utilization of new electrode materials with a high specific capacity to improve the energy density of supercapacitors remain challenging. Herein, an LaMnO3@NiCo2O4/carbon cloth (LMO@NCO/CC) composed of a multilayer flower-like nanochip array is prepared for the first time using an efficient electrodeposition method. This novel structure exploits the high conductivity of LaMnO3/carbon cloth (LMO@CC) to provide an efficient electron transport path for the outer layer of the NiCo2O4/carbon cloth (NCO@CC) nanoarrays, broadening the potential window. Due to the unique nanostructure configuration and the strong synergistic effect of the developed LMO@NCO/CC, the prepared electrodes show excellent supercapacitor performance. At a current density of 1 A g-1, LMO@NCO/CC has a higher specific capacitance value of 942 F g-1. The application value is extended through the fabrication of asymmetric supercapacitors with a maximum energy density of 49 Wh kg-1 and excellent cycle stability (the initial capacitance value remains 106 % after 10,000 cycles of charging and discharging at a high current density of 10 A g-1). Our work paves the way for the development of next-generation electrode materials for high-performance supercapacitors.

3.
Chemosphere ; 310: 136780, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36241122

RESUMO

Per- and polyfluoroalkyl substances (PFASs) levels in Indo-Pacific finless porpoises (Neophocaena phocaenoides) in the Pearl River Estuary (PRE), near the most economically developed region in China, have not been characterized. We measured the hepatic concentrations of twelve PFASs, including nine perfluoroalkyl carboxylic acids (PFCAs) and three perfluoroalkane sulfonic acids (PFSAs) in the finless porpoises (n = 21) collected from the PRE between 2007 and 2020. The average level of PFSAs was more than 2-times higher than that of PFCAs. The order of six dominant PFASs was perfluorooctane sulfonate (PFOS) > perfluoroundecanoic acid (PFUdA) > perfluorodecanoic acid (PFDA) > perfluorotridecanoic acid (PFTrDA) > perfluorononanoic acid (PFNA) > perfluorododecanoic acid (PFDoDA). The levels of Hepatic PFOS of 29% samples exceeded the no observable adverse effect level (NOAEL) values. The concentration of PFASs in males was significant higher than in females. PFASs levels were significantly negatively correlated with body length in males and positively correlated in females. PFASs levels in the PRE finless porpoises were lower than in humpback dolphins possibly due to different foraging habitat toward the coast and the consumption of less fish. PFCAs levels in finless porpoises from the western PRE were higher compared to Hong Kong, possibly due to the high-intensity sources of terrestrial anthropogenic pollutants. Significant increasing spatiotemporal trends of PFSAs, PFCAs and PFASs were found in finless porpoises from 2007 to 2020, suggesting a continuously increased risk of PFASs exposure for PRE cetaceans in the last decade.


Assuntos
Ácidos Alcanossulfônicos , Golfinhos , Fluorcarbonetos , Toninhas , Poluentes Químicos da Água , Masculino , Animais , Feminino , Monitoramento Ambiental , China , Ácidos Sulfônicos , Ácidos Carboxílicos , Poluentes Químicos da Água/análise
4.
Int Wound J ; 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36330591

RESUMO

The adjuvant effectiveness of nalbuphine in context of brachial plexus block (BPB) in patients undergoing upper-limb orthopaedic trauma surgery has remained uncertain. The purpose of this meta-analysis was to evaluate the analgesic benefit of mixing nalbuphine into local anaesthetics in BPB for wound pain from upper-limb trauma surgery. Primary outcome was the duration of analgesia. Seventeen trials (1104 patients) were analysed. Patients receiving nalbuphine have an increased weighted mean difference (WMD) 95% confidence interval of the duration of analgesia by 186.91 minutes (133.67 to 240.16) (P < 0.001). Compared to placebo, nalbuphine shorten the onset time of sensory and motor block by WMD of 2.59 (1.27 to 3.92) and 3.06 minutes (1.65 to 4.48) (P < 0.001), respectively. Meanwhile, nalbuphine prolonged the durations of sensory and motor block (P < 0.001). Qualitative and quantitative synthesis revealed no differences with regard to the outcomes related to side-effects. There is moderate-quality evidence that the addition of nalbuphine to local anaesthetics for BPB in patients undergoing upper-limb orthopaedic trauma surgery significantly prolongs the duration of analgesia, while preserving a similar safety-profile compared with local anaesthetics alone. However, these benefits should be further weighed against nalbuphine-related neurological safety in future studies.

5.
Cancer Commun (Lond) ; 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36331328

RESUMO

BACKGROUND: Although programmed cell death 1 (PD-1) blockade plus chemotherapy can significantly prolong the progression-free survival (PFS) and overall survival (OS) in first-line settings in patients with driver-negative advanced non-small-cell lung cancer (NSCLC), the predictive biomarkers remain undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy. METHODS: Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone. Tumor immune microenvironmental markers, including PD-1 ligand (PD-L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan-Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations. RESULTS: Responders had significantly higher CD8/PD-L1 (P = 0.015) or CD68/PD-L1 co-expression levels (P = 0.021) than non-responders in the camrelizumab plus chemotherapy group, while no difference was observed in the chemotherapy group. Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS (P = 0.002, P = 0.024; respectively) and OS (P = 0.006, P = 0.026; respectively) than those with low co-expression in camrelizumab plus chemotherapy group. When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification, significantly better PFS (P = 0.003) and OS (P = 0.032) were observed in high co-expression subgroups. The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features. Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression, the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups (both 13.0% vs. 0.0%, P = 0.023). Notably, enriched PI3K (P = 0.012) and cell cycle pathway (P = 0.021) were found in the CD8/PD-L1 co-expression group. CONCLUSION: Tumor immune microenvironmental marker expression, especially CD8/PD-L1 or CD68/PD-L1 co-expression, was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.

6.
Front Neurol ; 13: 1006227, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330427

RESUMO

Objectives: Traumatic intracerebellar hematoma (TICH) is a very rare entity with a high morbidity and mortality rate, and there is no consensus on its optimal surgical management. In particular, whether and when to place external ventricle drainage in TICH patients without acute hydrocephalus pre-operation is still controversial. Methods: A single-institutional, retrospective analysis of total of 47 TICH patients with craniectomy hematoma evacuation in a tertiary medical center from January 2009 to October 2020 was performed. Primary outcomes were mortality in hospital and neurological function evaluated by GOS at discharge and 6 months after the ictus. Special attention was paid to the significance of external ventricular drainage (EVD) in TICH patients without acute hydrocephalus on admission. Results: Analysis of the clinical characteristics of the TICH patients revealed that the odds of use of EVD were seen in patients with IVH, fourth ventricle compression, and acute hydrocephalus. Placement of EVD at the bedside can significantly improve the GCS score before craniotomy, as well as the neurological score at discharge and 6 months. Compared with the only hematoma evacuation (HE) group, there is a trend that EVD can reduce hospital mortality and decrease the occurrence of delayed hydrocephalus, although the difference is not statistically significant. In addition, EVD can reduce the average NICU stay time, but has no effect on the total length of stay. Moreover, our data showed that EVD did not increase the risk of associated bleeding and intracranial infection. Interestingly, in terms of neurological function at discharge and 6 month after the ictus, even though without acute hydrocephalus on admission, the TICH patients can still benefit from EVD insertion. Conclusion: For TICH patients, perioperative EVD is safe and can significantly improve neurological prognosis. Especially for patients whose GCS dropped by more than 2 points before the operation, EVD can significantly improve the patient's GCS score, reduce the risk of herniation, and gain more time for surgical preparation. Even for TICH patients without acute hydrocephalus on admission CT scan, EVD placement still has positive clinical significance.

7.
J Hazard Mater ; 443(Pt B): 130255, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36327844

RESUMO

Mining-impacted environments are distributed globally and have become increasingly recognized as hotspots of antibiotic resistance genes (ARGs). However, there are currently no reports on treatment technologies to deal with such an important environmental problem. To narrow this knowledge gap, we implemented a phytostabilization project in an acidic copper mine tailings pond and employed metagenomics to explore ARG characteristics in the soil samples. Our results showed that phytostabilization decreased the total ARG abundance in 0-10 cm soil layer by 75 %, which was companied by a significant decrease in ARG mobility, and a significant increase in ARG diversity and microbial diversity. Phytostabilization was also found to drastically alter the ARG host composition and to significantly reduce the total abundance of virulence factor genes of ARG hosts. Soil nutrient status, heavy metal toxicity and SO42- concentration were important physicochemical factors to affect the total ARG abundance, while causal mediation analysis showed that their effects were largely mediated by the changes in ARG mobility and microbial diversity. The increase in ARG diversity associated with phytostabilization was mainly mediated by a small subgroup of ARG hosts, most of which could not be classified at the genus level and deserve further research in the future.

8.
J Virol ; : e0087922, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36377874

RESUMO

The glycan loop of Zika virus (ZIKV) envelope protein (E) contains the glycosylation site and has been well documented to be important for viral pathogenesis and transmission. In the present study, we report that deletions in the E glycan loop, which were recorded in African ZIKV strains previously, have re-emerged in their contemporary Asian lineages. Here, we generated recombinant ZIKV containing specific deletions in the E glycan loop by reverse genetics. Extensive in vitro and in vivo characterization of these deletion mutants demonstrated an attenuated phenotype in an adult A129 mouse model and reduced oral infections in mosquitoes. Surprisingly, these glycan loop deletion mutants exhibited an enhanced neurovirulence phenotype, and resulted in a more severe microcephalic brain in neonatal mouse models. Crystal structures of the ZIKV E protein and a deletion mutant at 2.5 and 2.6 Å, respectively, revealed that deletion of the glycan loop induces encephalitic flavivirus-like conformational alterations, including the appearance of perforations on the surface and a clear change in the topology of the loops. Overall, our results demonstrate that the E glycan loop deletions represent neonatal mouse neurovirulence markers of ZIKV. IMPORTANCE Zika virus (ZIKV) has been identified as a cause of microcephaly and acquired evolutionary mutations since its discovery. Previously deletions in the E glycan loop were recorded in African ZIKV strains, which have re-emerged in the contemporary Asian lineages recently. The glycan loop deletion mutants are not glycosylated, which are attenuated in adult A129 mouse model and reduced oral infections in mosquitoes. More importantly, the glycan loop deletion mutants induce an encephalitic flavivirus-like conformational alteration in the E homodimer, resulting in a significant enhancement of neonatal mouse neurovirulence. This study underscores the critical role of glycan loop deletion mutants in ZIKV pathogenesis, highlighting a need for global virological surveillance for such ZIKV variants.

9.
Neurol India ; 70(5): 1824-1829, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36352573

RESUMO

Background: Although the asterion has long been used as a skeletal surface marker of the transverse-sigmoid sinuses junction (TSSJ) point in the retrosigmoid approach, abundant evidence shows that the relationship between asterion and TSSJ point varies greatly. In recent years, new technologies have been developed, such as neuronavigation and three-dimensional volume rendering imaging, that can guide in exposing the TSSJ point individually. However, they are not only expensive but also difficult to apply in emergency surgery. Objective: To introduce a quick, practical, and low-cost new method for locating the TSSJ point precisely. Methods: In this retrospective before-after study, the test group located the TSSJ point with our new method during a 6-month period, while the control group used asterion as a surface landmark to estimate the TSSJ during the preceding 6 months. The primary outcome is the immediate exposure rate of the TSSJ point by the initial burr hole. Results: There were 60 patients in both control and test groups as no significant difference in the general clinical characteristics of both groups were observed. The new three-step method significantly increased the TSSJ exposure rate by initial burr hole compared with the control group (96.67% vs. 53.33%, P = 0.0002). Moreover, the total bone loss and craniotomy duration were significantly reduced by the new method. Incidence of sinus injury (10% vs. 6.6%), post-operation infection (3.33% vs. 3.33%), and CSF leakage (3.33% vs. 0%) were similar. Conclusions: The novel three-step approach accurately locates TSSJ points in retrosigmoid craniotomy, reduces bone defects, saves time, and does not increase the risk of sinus injury, infection, and CSF leakage.


Assuntos
Cavidades Cranianas , Craniotomia , Humanos , Estudos Retrospectivos , Estudos Controlados Antes e Depois , Cavidades Cranianas/diagnóstico por imagem , Cavidades Cranianas/cirurgia , Craniotomia/métodos , Imageamento por Ressonância Magnética
10.
Front Nutr ; 9: 1019615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36352906

RESUMO

Background and aims: Overweight or obesity is one of the most prevalent health burdens in companion pets and predisposes subjects to multiple comorbidities and reduced longevity. Dietary management and sufficient exercise are effective options for weight loss but challenged by modern lifestyle and calorie control-triggered malnutrition. Therefore, this study aimed to develop a formulated obesity control diet characterized by protein- and fiber-rich diet and supplemented with astaxanthin. We systemically evaluated global influences of the designed weight-loss diet on metabolic homeostasis in an obese beagle model. Materials and methods: Beagles were induced for obesity by a 24-week HFD treatment and then included into weight-loss programs. Briefly, obese beagles were randomly assigned to two groups that were fed with a formulated weight-loss diet or control diet, respectively. Body weight and body condition scoring (BCS) were analyzed biweekly. Computed tomography (CT), nuclear magnetic resonance imaging (MRI) measurements, and blood and adipose tissue biopsies were collected at 0 and 8 weeks. Plasma lipids and adipocyte size were also measured after 8 weeks of weight-loss diet feeding. The global influence of the formulated diet on the whole spectrum of gene panels were examined by adipose RNA assays. Results: Twenty-four weeks of continuous HFD feeding significantly induced obesity in beagles, as evidenced by increased body weight, BCS, abdominal fat mass, and serum lipid levels. The obese and metabolic condition of the modeled canine were effectively improved by an 8-week weight-loss diet administration. Importantly, we did not observe any side effects during the weight loss duration. Transcriptional analysis of adipose tissues further supported that a weight-loss diet significantly increased energy metabolism-related pathways and decreased lipid synthesis-related pathways. Conclusion: The prescribed weight-loss diet exhibited profound benefits in canine weight management with well safety and palatability. These findings support effective strategies of nutritional management and supplementation approaches for weight control in companion animals.

11.
Cells ; 11(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36359751

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an infectious disease that has become a serious burden on global public health. This study screened and yielded specific nanobodies (Nbs) against SARS-CoV-2 spike protein receptor binding domain (RBD), following testing its basic characteristics. A nanobody phage library was established by immunizing a camel with RBD protein. After three rounds of panning, the positive colonies were screened by enzyme-linked immunosorbent assay (ELISA). By sequencing, four different sequences of nanobody gene fragments were selected. The four nanobody fusion proteins were expressed and purified, respectively. The specificity and affinity of the four nanobodies were identified by ELISA. Our results showed that an immune phage display library against SARS-CoV-2 has been successfully constructed with a library capacity of which was 4.7 × 108 CFU. The four purified nanobodies showed specific high-affinity binding SARS-CoV-2 S-RBD. Among these, the antigen binding affinity of Nb61 was more comparable to that of commercial rabbit anti-SARS-CoV-2 S-RBD antibodies. In sum, our study has obtained four nanobody strains against SARS-CoV-2 S-RBD with significant affinity and specificity, therefore laying an essential foundation for further research as well as the applications of diagnostic and therapeutic tools of SARS-CoV-2.


Assuntos
COVID-19 , Anticorpos de Domínio Único , Animais , Humanos , Coelhos , Glicoproteína da Espícula de Coronavírus/química , Anticorpos Neutralizantes , SARS-CoV-2 , Camelus
12.
J Med Chem ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36351049

RESUMO

To enhance the affinity of the human epidermal growth receptor 2 (HER2) targeted peptide developed previously, bispecific fusion peptides P1GCGT1 and P1GCGCGT1 were designed using an in silico approach. Molecular dynamic simulation showed that both peptides strongly interacted with HER2 domains II and IV. Compared with peptides targeting each single domain, P1GCGT1 and P1GCGCGT1 could bind to HER2 more significantly and targeted HER2-positive cells specifically. Additionally, both peptides were used to generate peptide-drug conjugates with camptothecin (CPT), among which I-1 and I-4 were screened for enhanced cellular activity and selectivity. Biological evaluation demonstrated that I-1 and I-4 induced cell apoptosis, promoted cell cycle arrestin S-phase, and inhibited Topo I activity. The binding affinity assay and confocal analysis revealed that I-1 and I-4 were effective at targeting HER2. Moreover, I-1 and I-4 showed better stability than single targeting peptide and presented enhanced antitumor activity and safety than CPT in tumor-bearing mice.

13.
Inorg Chem ; 61(45): 17993-18001, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36330783

RESUMO

The involvement of the 2-phosphaethynolate anion species with ambident nucleophilic properties serves as an essential protocol for synthesizing oxygen-bound or phosphorus-bound complexes. This work mainly describes the synthesis and characterization of U, Th, and Ti phosphaethynolate complexes featuring a preferential O-coordination fashion. Among these complexes, the first examples of a Ti(IV)-OCP complex 3A, Th(IV)-OCP complex 3B, and U(IV)-OCP complex 3C were assembled by a salt metathesis reaction between M(TrapenTMS)(Cl) (M = Ti, Th, U) and NaOCP(dioxane)2.5 and were all crystallographically characterized. The structural similarity of this series of phosphaethynolate complexes allows us to compare the bonding properties of d- and f-block elements in the corresponding compounds. The well-established density functional theory (DFT) computational method was employed to explore the electronic structures and covalency in M-O bonding, and the results showed a consistent pattern. The calculation result showed that 2-phosphaethynolate complexes exhibited the covalency trend of U-O > Th-O > Ti-O due to the involvement of 5f orbitals.

14.
Environ Sci Technol ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36345731

RESUMO

More and more contaminants in dust have been found to be glucocorticoid receptor (GR) disrupting chemicals. However, little is known about the related potency and responsible toxicants, especially for the main bioaccessible ones in dust. An effect-directed analysis (EDA)-based workflow was developed, including solvent-based exhaustive extraction/tenax-assisted bioaccessible extraction (TBE), high-throughput bioassays, suspect and non-target analysis, as well as in silico candidate selection, for a more realistic identification of responsible contaminants in dust. None of the 39 dust samples from 23 cities in China exhibited GR agonistic activity, while GR antagonistic potencies were detected in 34.8% of samples, being significantly different from the high detection frequency of GR agonistic activities in other environmental media. The GR antagonistic potencies of the dust samples were all reduced after bioaccessible extraction. The mean bioaccessibility of GR antagonistic potency compared with the related exhaustive extracts was 36.8%, and the lowest value was 9%. By using in silico candidate selection, greater than 99% candidate chemical structures which were found by a non-target screening strategy were removed. Di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), and nicotine (NIC) were responsible for the activities of the exhaustive extracts of dust, contributing up to 91% potencies. DiBP and DnBP were also responsible for the bioaccessible activities, contributing up to 79% potencies. However, the contribution from NIC decreased significantly and can be ignored because of its low bioaccessibility. This study suggests that the improved workflow combining extraction, reporter gene bioassays, suspect and non-target analysis, as well as in silico candidate selection is useful for EDA analysis in dust samples. In addition, exhaustive extraction may overestimate the risk of contaminants, while bioaccessibility evaluation based on bioaccessible extraction is essential in both effect evaluation and toxicant identification.

15.
ACS Med Chem Lett ; 13(11): 1730-1738, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36385928

RESUMO

Tyrosine kinase 2 (TYK2) mediates the interleukin-23 (IL-23), IL-12, and type I interferon (IFN)-driven signal responses that are critical in autoimmune diseases. Here, a series of novel derivatives with an N-(methyl-d 3)pyridazine-3-carboxamide skeleton that bind to the TYK2 pseudokinase domain were designed, synthesized, and evaluated. Among them, compound 30 demonstrated more excellent inhibitory potency against STAT3 phosphorylation than the positive control deucravacitinib. In addition to JAK isoform selectivity, compound 30 exhibited good in vivo and in vitro pharmacokinetic properties. Furthermore, compound 30 was orally highly effective in both IL-23-driven acanthosis and anti-CD40-induced colitis models. Together, these findings support compound 30 as a promising candidate for therapeutic applications in autoimmune diseases.

16.
Front Pharmacol ; 13: 1015846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386137

RESUMO

Epimedii Folium (EF, Epimedium brevicornu Maxim.), a traditional botanical drug, is famous for treating bone fractures, joint diseases, and several chronic illnesses. However, some studies indicated that EF could induce idiosyncratic drug-induced liver injury (IDILI) in the clinic. The NLRP3 inflammasome plays a crucial role in the pathogenesis of various human diseases, including IDILI. In the present study, we showed that epimedin B could specifically facilitate nigericin- or ATP-induced NLRP3 inflammasome activation under synergistic induction of mitochondrial reactive oxygen species. Moreover, epimedin B resulted in activation of Caspase-1 and IL-1ß secretion in a lipopolysaccharide (LPS)-mediated susceptibility mouse model. MCC950 pretreatment completely abrogated activation of the NLRP3 inflammasome and prevented liver injury. Importantly, several studies have confirmed that some active constituents of EF could enhance activation of the NLRP3 inflammasome and may be involved in the pathogenesis of EF-IDILI. No reports are available on whether the structure-activity relationship associated with the immunostimulatory activity in EF contributes to the pathogenesis of EF-IDILI. These findings have changed our conventional understanding about the more glycogen, the more immunostimulatory activity.

17.
Inorg Chem ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36394920

RESUMO

The development of green primary explosives has become a "holy grail" of energetic materials research. Cu-based 5-nitrotetrazolate is considered one of the most promising candidates due to its excellent blasting power and environmentally benign nature. However, synthesizing Cu-based 5-nitrotetrazolate controllably and securely remains highly challenging. Herein, room-temperature anodization of metallic Cu and a Cu(I)-imidazole nanowire array on copper substrates in a sodium 5-nitrotetrazolate electrolyte leads to in situ electrosynthesis of Cu(I) 5-nitrotetrazolate (DBX-1, CuNT) and its analogue, Cu(II) 5-nitrotetrazolate [Cu(NT)2], respectively. Both obtained CuNT and Cu(NT)2 films demonstrate remarkable energy output and good laser-induced ignition performance. The thermal stability (Tp = 291 °C) and electrostatic safety (E50 = 2.54 mJ) of CuNT proved to be superior to those of Cu(NT)2 (Tp = 257 °C, and E50 = 0.57 mJ). Remarkably, this study provides an exciting new method for the rational design and development of Cu-based 5-nitrotetrazolate as a primary explosive for advanced initiating applications.

18.
Am J Transl Res ; 14(10): 7164-7171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36398263

RESUMO

OBJECTIVE: To investigate the prevalence of myopia among children and adolescents in a local area (Liyang City) of China and analyze the influencing factors, so as to formulate corresponding preventive measures. METHODS: A questionnaire survey was conducted, mainly investigating subjects' age, gender, residence (urban/rural areas), parental myopia, daily time spent outdoors, daily sleep time, distance between computer screen and eyes, less than one punch (10 cm) from the chest to the edge of the desk when reading and writing, one inch (3 cm) between finger and pen tip when writing, number of in-school physical education (PE) classes, length of TV watching, and size of TV. The myopia of all participants was recorded. RESULTS: This study enrolled 7,948 children and adolescents, including 4,733 (59.55%) cases of myopia, 1,025 (12.90%) of astigmatism, 251 (3.16%) of hyperopia, and 699 (8.79%) of anisometropia respectively. There were 2,519 (53.22%) cases of myopia in the left eye and 2,214 (46.78%) in the right eye. Low, moderate, and high myopia were determined in 2,682 (56.67%), 1,583 (33.45%), and 468 (9.89%), respectively. In terms of spherical equivalent (SEQ), a statistically lower SEQ was observed in urban areas (-1.56±0.46 d) versus suburban counties (-1.17±0.33 d), and in females (-1.68±0.30 d) compared with males (-1.17±0.44 d). The mean SEQ gradually decreased with age. The prevalence of myopia was 63.84% (2,436/3,816) in females, statistically higher than that of 55.59% (2,197/4,132) in males (χ2=56.00, P < 0.0001). The incidence of myopia was statistically higher in urban areas (67.93% [3,321/4,889]) versus rural areas (46.16% [1,412/3,059]). Parental myopia, one inch between finger and pen tip when writing, daily time spent outdoors, daily sleep time, distance between computer screen and eyes, less than one punch from the chest to the edge of the desk when reading and writing, number of in-school PE classes, and daily length of TV watching were significantly correlated with the occurrence of myopia. CONCLUSIONS: Parents are advised to pay attention to daily time spent outdoors, sleep time, distance between the computer screen and the eyes, distance between the chest and the edge of the table when reading and writing, and length of TV watching of their children. As far as schools are concerned, PE activity time should be properly maintained to ensure that children have enough outdoor exercise time to reduce eye fatigue.

19.
Cell Commun Signal ; 20(1): 177, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376931

RESUMO

BACKGROUND: Loss-of-function (LOF) mutations of JAK1, a member of the JAK kinase family, were frequently observed in EC, indicating that JAK1 may act as a tumor suppressor, at least in EC. However, the mechanism of JAK1 mediated regulation of tumorigenesis remains poorly understood. METHODS: The genetic alterations of JAK1 in EC using latest sequencing dataset of EC deposited in TCGA database. The RNA-Seq dataset of EC and normal endometrial tissues from TCGA cohort was analyzed. The expression of JAK1 in EC and normal endometrial tissues were investigated using immunohistochemistry. The expression levels of genes in endometrial cancer cells were detected by quantitative reverse transcription-PCR (RT-qPCR) and western blotting. JAK1 protein was efficiently depleted by the two shRNAs. HIF1/2-α protein was efficiently depleted by siRNAs. JAK1 overexpressed EC cells were generated by an expressing plasmid. The proliferation and migration ability of cancer cells were evaluated by CCK8, colony formation assays and transwell assays. The global transcriptomic changes in JAK1-depleted KLE cells were investigated using RNA-Seq. Gene Ontology (GO) Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to identify the most significant pathways that were altered in JAK1-depleted KLE cells. The physical association between HIF-1/2α and JAK1 using co-immunoprecipitation (co-IP) assays. RESULTS: In the present study, we found that JAK1 was frequently mutated and downregulated in EC. JAK1 knockdown promotes EC cell proliferation and migration. JAK1 overexpression reduces EC cell proliferation and migration. We examined the transcriptional profiling changes in JAK1-depleted EC cells and unexpectedly found that the hypoxia inducible factor (HIF) pathway was activated. Mechanistically, JAK1 interacts with HIF-1/2α, and reduces HIF1/2-α protein expression under hypoxia. HIF-1/2α knockdown reverses the JAK1 knockdown-induced growth and migration of EC cells under hypoxia. JAK1 knockdown or pharmacological inhibition of JAK1 kinase activity by Ruxolitinib upregulates transcription of HIF target genes under hypoxia. JAK1 overexpression downregulates transcription of HIF target genes under hypoxia. CONCLUSIONS: These findings provide novel insights into the functional link between JAK1 LOF mutations and abnormal HIF pathway activation in EC and suggest that pharmacological inhibition of HIF1/2 represents a promising therapeutic strategy targeting JAK1-mutated ECs. Video Abstract.


Assuntos
Neoplasias do Endométrio , Humanos , Feminino , Janus Quinase 1 , Neoplasias do Endométrio/genética , Transdução de Sinais , Proliferação de Células , RNA Interferente Pequeno/metabolismo , Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Hipóxia Celular , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral
20.
Clin Transl Sci ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369801

RESUMO

Novel hormonal agents (NHAs) have significantly improved outcomes in men with advanced prostate cancer. However, it remains unclear whether NHAs are associated with subsequent cognitive impairment. Thus, we sought to perform a network meta-analysis to compare the risk of cognitive impairment across NHA types. Databases (PubMed, Embase, Scopus, and Web of Science), trial registries (Clinicaltrial.gov), the European Medicines Agency, and the US Food and Drug Administration drug safety reports were searched from inception through July 30, 2021. Eligible studies were clinical trials evaluating the risk of cognitive impairment between NHAs and placebo/standard care. Two independent investigators extracted the data and performed quality assessments using the Cochrane Risk of Bias Tool and ROBINS-I. We estimated the risk ratios by the frequentist approach and calculated the ranking probabilities of all treatments with the surface under the cumulative ranking probabilities. The primary outcome and secondary outcome were odds ratio (OR) and incidence rate ratio of cognitive impairment, respectively. We identified 15 trials with 14,723 participants comparing HNAs with placebo/standard care. Treatments associated with cognitive impairment, from the most to the least, were enzalutamide (OR, 3.66; 95% confidence interval [CI], 2.84-4.73), apalutamide (OR, 1.76; 95% CI, 1.08-2.87), abiraterone acetate (OR, 1.64; 95% CI, 1.01-2.45), and darolutamide (OR, 1.11 95% CI, 0.51-2.39). After adjustment of treatment time duration, enzalutamide still had the highest risk of cognitive impairment with an incidence rate ratio of 2.17 (95% CI, 1.65-2.78). These findings suggest that NHAs, especially enzalutamide, may increase the risk of cognitive impairment compared with placebo/standard care.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...