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1.
Front Plant Sci ; 13: 859290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498696

RESUMO

Tomato fruit phenotypes are important agronomic traits in tomato breeding as a reference index. The traditional measurement methods based on manual observation, however, limit the high-throughput data collection of tomato fruit morphologies. In this study, fruits of 10 different tomato cultivars with considerable differences in fruit color, size, and other morphological characters were selected as samples. Constant illumination condition was applied to take images of the selected tomato fruit samples. Based on image recognition, automated methods for measuring color and size indicators of tomato fruit phenotypes were proposed. A deep learning model based on Mask Region-Convolutional Neural Network (R-CNN) was trained and tested to analyze the internal structure indicators of tomato fruit. The results revealed that the combined use of these methods can extract various important fruit phenotypes of tomato, including fruit color, horizontal and vertical diameters, top and navel angles, locule number, and pericarp thickness, automatically. Considering several corrections of missing and wrong segmentation cases in practice, the average precision of the deep learning model is more than 0.95 in practice. This suggests a promising locule segmentation and counting performance. Vertical/horizontal ratio (fruit shape index) and locule area proportion were also calculated based on the data collected here. The measurement precision was comparable to manual operation, and the measurement efficiency was highly improved. The results of this study will provide a new option for more accurate and efficient tomato fruit phenotyping, which can effectively avoid artificial error and increase the support efficiency of relevant data in the future breeding work of tomato and other fruit crops.

2.
Drug Metab Dispos ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35545256

RESUMO

Fragment crystallizable (Fc) fusion is commonly used for extending the half-life of biotherapeutics such as cytokines. In this work, we studied the pharmacokinetics of Fc-fused interleukin-10 (IL-10) proteins that exhibited potent anti-tumor activity in mouse syngeneic tumor models. At pharmacologically active doses of {greater than or equal to}0.1 mg/kg, both mouse Fc-mouse IL-10 and human Fc-human IL-10, constructed as the C-terminus of the Fc domain fused with IL-10 via a glycine-serine polypeptide linker, exhibited nonlinear pharmacokinetics after intravenous administration to mice at the doses of 0.05, 0.5, and 5 mg/kg. With a nominal dose ratio of 1:10:100; the ratio of the area under the curve for mouse Fc-mouse IL-10 and human Fc-human IL-10 was 1:181:1830 and 1:75:633, respectively. In contrast, recombinant mouse or human IL-10 proteins exhibited linear pharmacokinetics in mice. Compartmental analysis, using the Michaelis-Menten equation with the in vitro IL-10 receptor alpha binding affinity inputted as the Km, unified the pharmacokinetic data across the dose range. Additionally, non-target-mediated clearance estimated for fusion proteins was ~200-fold slower than that for cytokines, causing the manifestation of target-mediated drug disposition (TMDD) in the fusion protein pharmacokinetics. The experimental data generated with a mouse IL-10 receptor alpha-blocking antibody and a human Fc-human IL-10 mutant with a reduced receptor binding affinity showed significant improvements in pharmacokinetics, supporting TMDD as the cause of nonlinearity. Target expression and its effect on pharmacokinetics must be determined when considering using Fc as a half-life extension strategy, and pharmacokinetic evaluations need to be performed at a range of doses covering pharmacological activity. Significance Statement Target-mediated drug disposition can manifest to affect the pharmacokinetics of a fragment crystallizable (Fc)-fused cytokine when the non-target-mediated clearance of the cytokine is decreased due to neonatal Fc receptor-mediated recycling and molecular weight increases that reduce the renal clearance. The phenomenon was demonstrated with interleukin-10 Fc-fusion proteins in mice at pharmacologically active doses. Future drug designs using Fc as a half-life extension approach for cytokines need to consider target expression and its effect on pharmacokinetics at relevant doses.

3.
Drug Des Devel Ther ; 16: 1349-1363, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547866

RESUMO

Purpose: Proton pump inhibitors, as the first-line drugs for treating gastroesophageal reflux disease (GERD), are unable to completely relieve patients' symptoms and patients are prone to recurrence after prolonged drug withdrawal. Thus, it is crucial to find herbal medicines as a complementary and alternative treatment. Hewei Jiangni granule (HWJNG) is a classical Chinese medicinal formula with clinical therapeutic effects on GERD, but its pharmacological mechanism of action remains unclear. This study aimed to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. Methods: A network pharmacology approach was applied to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. The active ingredients of HWJNG, as well as therapeutic targets of GERD were acquired from specialized databases. The "herb-ingredient-gene-target" network for HWJNG in GERD treatment was built. The protein-protein interaction (PPI) network was constructed to screen the core coincident targets. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The core targets and signaling pathways associated with the anti-neurogenic inflammatory effect were partially verified via experiments in vivo at molecular level. Results: In total, 179 chemical ingredients in HWJNG and 298 intersection targets between GERD and HWJNG were selected from databases. A large proportion of core targets and top signaling pathways were involved in neurogenic inflammation. HWJNG significantly alleviated pathological injuries of esophagus and reversed dilated intracellular spaces. Additionally, HWJNG markedly inhibited the excessive release of inflammatory cytokines such as interleukin (IL)-1ß, IL-6, tumor necrosis factor receptor (TNF-a), as well as regulated stimulation sensors including transient receptor potential vanilloid type 1 (TRPV1) and its related neuroinflammatory mediators in GERD mice. Conclusion: HWJNG is a promising therapeutic strategy for GERD treatment via regulation of multiple targets and pathways, its effects in alleviating neurogenic inflammation are especially acknowledged.

4.
Radiat Oncol ; 17(1): 91, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35549962

RESUMO

BACKGROUND: To analyze the prognostic factors associated with stage IB-IVA cervical cancer in patients who underwent concurrent chemoradiation therapy (CCRT) and to compare the clinical toxicities and dosimetric parameters of organs at risk between the different radiotherapy techniques. METHODS: This retrospective study enrolled 93 patients with stage IB-IVA cervical cancer who underwent definitive CCRT between April 2009 and December 2017. Nine patients (9.7%) received 3DCRT, 43 patients (46.2%) underwent VMAT, and 41 patients (44.1%) received tomotherapy, and all of them followed by brachytherapy using a 2D planning technique. The treatment outcomes and related prognostic factors were analyzed. We also compared the clinical toxicities and dosimetric parameters between the different techniques used for the last 30 patients. RESULTS: With a median follow-up of 52.0 months, the 5-year overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastases-free survival (DMFS) were analyzed. In a Cox proportional hazards regression model, pretreatment SCC Ag > 10 ng/mL was a significant prognostic factor for PFS (hazard ratio [HR] 2.20; 95% confidence interval [CI] 1.03-4.70; P = 0.041), LRRFS (HR, 3.48; 95% CI 1.07-11.26; P = 0.038), and DMFS (HR 2.80; 95% CI 1.02-7.67; P = 0.045). Increasing the rectal volume receiving a radiation dose exceeding 30 Gy (V30 of rectum; odds ratio [OR] 1.15; 95% CI 1.10-1.30; P = 0.03) was associated with a higher possibility of ≥ Grade 2 acute radiation therapy (RT)-related diarrhea. The median rectal V30 values were 56.4%, 97.5%, and 86.5% for tomotherapy, 3-dimensional conformal radiation therapy (3DCRT), and volumetric modulated arc therapy (VMAT), respectively (P < 0.001). In addition, the chance of experiencing ≥ Grade 2 acute diarrhea were 10.0%, 66.7%, and 54.5% for tomotherapy, 3DCRT, and VMAT, respectively (P = 0.029). CONCLUSIONS: Patients with pretreatment SCC Ag ≤ 10 ng/mL have better PFS, LRRFS, and DMFS than those with pretreatment SCC Ag > 10 ng/mL. The rectal V30 is a significant predictor of severe acute diarrhea. Tomotherapy significantly decreased the rectal V30, reducing the severity of acute RT-related diarrhea during external beam RT. Trial registration This study was approved by the institutional review board at Kaohsiung Medical University Hospital. The registration number is KMUHIRB-E(I)-20190054 and retrospectively registered on 2019/3.

5.
Neurosci Bull ; 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35570231

RESUMO

Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (Aß)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aß deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.

6.
Int J Gen Med ; 15: 4753-4769, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571289

RESUMO

Background: Pyroptosis is a novel form of cell death that plays a significant role in cancer, while the prognostic values of pyroptosis-related genes in gliomas have not been revealed. Methods: We analyzed the RNA-seq and clinical data of gliomas from the University of California Santa Cruz (UCSC) Xena database to determine differentially expressed pyroptosis-related genes. Based on these genes, a pyroptosis genes signature was constructed after univariate Cox analysis and Lasso Cox analyses. The sensitivity and specificity of pyroptosis genes signature were verified by the Chinese Glioma Genome Atlas (CGGA) dataset. Finally, we explored the association of risk signatures with tumor microenvironment and immune cell infiltration. Results: Of 15 differentially expressed pyroptosis-related genes, three genes of BCL2 associated X (BAX), caspase 3 (CASP3), and caspase 4 (CASP4) were used to construct the risk signature. The effectiveness of risk signature for predicting survival at 1, 3, 5 years was performed by the receiver operating characteristic curve (ROC), and the area under curves (AUC) was 0.739, 0.817, and 0.800, respectively. Functional enrichment results showed signal transduction, cell adhesion, immune response, and inflammatory response were enriched. The immune analysis revealed that pyroptosis had a remarkable effect on the immune microenvironment. Conclusion: In this study, we constructed a pyroptosis-related gene signature, which can serve as a potential biomarker for predicting the survival of glioma patients. Additionally, we suggested that pyroptosis may promote gliomas development by inducing chronic inflammation microenvironment.

7.
Front Cell Infect Microbiol ; 12: 854505, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573799

RESUMO

Objective: Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community acquired pneumonia. With the outbreak of coronavirus disease 2019 (COVID-19), the prevalence of some infectious respiratory diseases has varied. Epidemiological features of M. pneumoniae in children from Beijing (China) before and during the COVID-19 pandemic were investigated. Methods: Between June 2016 and May 2021, a total of 569,887 children with respiratory infections from Children's Hospital Affiliated to Capital Institute of Pediatrics (Beijing, China) were included in this study. M. pneumoniae specific-IgM antibody in serum specimens of these patients was tested by a rapid immunochromatographic assay kit. The relevant clinical data of M. pneumoniae-positive cases were also collected, and analyzed by RStudio software. Results: The results showed that 13.08% of collected samples were positive for M. pneumoniae specific-IgM antibody. The highest annual positive rate was 17.59% in 2019, followed by 12.48% in 2018, 12.31% in 2017, and 11.73% in 2016, while the rate dropped to 8.9% in 2020 and 4.95% in 2021, with significant difference. Among the six years, the positive rates in summer and winter seasons were significantly higher than those in spring and autumn seasons (p < 0.001). The positive rate was the highest in school-age children (22.20%), and lowest in the infant group (8.76%, p < 0.001). The positive rate in boys (11.69%) was lower than that in girls (14.80%, p < 0.001). There were no significant differences in different seasons, age groups, or genders before and during the COVID-19 pandemic (p > 0.05). Conclusions: Our study demonstrated that an M. pneumoniae outbreak started from the summer of 2019 in Beijing. After the COVID-19 pandemic outbreak in the end of 2019, the M. pneumoniae positive rates dropped dramatically. This may be due to the restrictive measures of the COVID-19 pandemic, which effectively controlled the transmission of M. pneumoniae. The relationships between M. pneumoniae positive rates and season, age, and gender were not statistically significant before and during the COVID-19 pandemic.

8.
Transl Psychiatry ; 12(1): 194, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538065

RESUMO

Angiostatin, an endogenous angiogenesis inhibitor generated by the proteolytic cleavage of plasminogen, was recently reported to contribute to the development of Alzheimer's disease (AD). However, whether there are pathological changes in angiostatin levels in individuals with AD dementia is unclear, and whether plasma angiostatin has a relationship with major AD pathological processes and cognitive impairment remains unknown. To examine plasma angiostatin levels in patients with AD dementia and investigate the associations of angiostatin with blood and cerebrospinal fluid (CSF) AD biomarkers, we conducted a cross-sectional study including 35 cognitively normal control (CN) subjects and 59 PiB-PET-positive AD dementia patients. We found that plasma angiostatin levels were decreased in AD dementia patients compared to CN subjects. Plasma angiostatin levels were negatively correlated with plasma Aß42 and Aß40 levels in AD dementia patients and positively correlated with CSF total tau (t-tau) levels and t-tau/Aß42 in AD dementia patients with APOE-ε4. In addition, plasma angiostatin levels had the potential to distinguish AD from CN. These findings suggest a link between angiostatin and AD pathogenesis and imply that angiostatin might be a potential diagnostic biomarker for AD.

9.
Front Microbiol ; 13: 865227, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531293

RESUMO

Wolbachia is a maternally inherited bacterium that is widely distributed among arthropods, in which it manipulates the reproduction of its hosts. Phage WO is the only bacteriophage known to infect Wolbachia, and may provide benefit to its host or arthropods. We screened for the presence of phage WO in Wolbachia-infected butterfly species for the first time, to investigate their diversity and evolutionary dynamics. All Wolbachia-infected butterfly species, including members of the families Hesperiidae, Lycaenidae, Nymphalidae, Papilionidae, and Pieridae, were found to harbor phage WO. Interestingly, 84% of 19 butterfly species, which were infected with a single Wolbachia strain harbored high levels of multiple phage types (ranging from 3 to 17 types), another three species harbored one or two phage types. For Wolbachia strains (ST-41, ST-19, ST-125 and ST-374) shared among various butterfly species, their host insects all harbored multiple phage types, while two Wolbachia strains (ST-297 and ST-wPcau) were found to infect one butterfly species, whose insect hosts harbored a single phage type, suggesting that horizontal transfer of Wolbachia between insects increased the likelihood of exposure to phages, resulting in increased phage genetic diversity. Twelve horizontal transmission events of phage WO were found, which shared common phage WO types among different Wolbachia strains associated with butterflies. Most horizontal transfer events involved different Wolbachia supergroups (A and B). Horizontal acquisition of phage WO might also occur between eukaryotes without Wolbachia transfer. Furthermore, 22 putative recombination events were identified in 13 of 16 butterfly species which harbored multiple phage types. These results showed that horizontal transfer of Wolbachia caused it to be exposed to the phage gene pool, and that horizontal transmission of phage WO, as well as intragenic recombination were important dynamics for phage WO genome evolution, which effectively promoted the high level of phage WO diversity associated with butterflies.

10.
Polymers (Basel) ; 14(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35567059

RESUMO

Herein, this work aims to fabricate well-ordered nanonetwork epoxy resin modified with poly(butyl acrylate)-b-poly(methyl methacrylate) (PBA-b-PMMA) block copolymer (BCP) for enhanced energy dissipation using a self-assembled diblock copolymer of polystyrene-b-poly(dimethylsiloxane) (PS-b-PDMS) with gyroid and diamond structures as templates. A systematic study of mechanical properties using nanoindentation of epoxy resin with gyroid- and diamond-structures after modification revealed significant enhancement in energy dissipation, with the values of 0.36 ± 0.02 nJ (gyroid) and 0.43 ± 0.03 nJ (diamond), respectively, when compared to intrinsic epoxy resin (approximately 0.02 ± 0.002 nJ) with brittle characteristics. This enhanced property is attributed to the synergic effect of the deliberate structure with well-ordered nanonetwork texture and the toughening of BCP-based modifiers at the molecular level. In addition to the deliberate structural effect from the nanonetwork texture, the BCP modifier composed of epoxy-philic hard segment and epoxy-phobic soft segment led to dispersed soft-segment domains in the nanonetwork-structured epoxy matrix with superior interfacial strength for the enhancement of applied energy dissipation.

11.
Artigo em Inglês | MEDLINE | ID: mdl-35507426

RESUMO

The adhesion between flexible epidermal sensors and human skin is essential for maintaining the stable functionality of the sensors. However, it is still challenging for epidermal electronic devices to achieve durable adhesion to the surface of the skin, especially under sweaty or humid conditions. Here, we report a silk fibroin-polyacrylamide (SF-PAAm) double network (DN) hydrogel adhesive with excellent biocompatibility, strong and durable adhesion on wet surfaces, and tunable adhesive properties. The hydrophilic PAAm network greatly improves the water retention capability of the DN hydrogel and reduces the ß-sheet crystalline content of SF, leading to excellent adhesive properties of the hydrogel across a wide range of humidity. The SF-PAAm DN hydrogel adhesive can be readily integrated with different epidermal sensor arrays and performs very well in real-time on-body sweat sensing. The SF-PAAm DN hydrogels have great potential for application in various epidermal healthcare sensors as well as medical adhesives for other medical applications.

12.
Org Lett ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533379

RESUMO

Herein, chiral Brønsted acid-catalyzed intramolecular asymmetric allylic alkylation of indoles with allylic primary alcohols is described. The allyl alcohols were directly employed as the allylic precursors in this metal-free protocol, without preactivation or any additional activating reagents. This method provides the convenient synthesis of a broad range of functionalized tetrahydrocarbazoles in excellent yields (≤97%) with good enantioselectivity (≤93% ee). The optimal conditions are compatible for gram-scale reaction.

13.
Sci Rep ; 12(1): 6955, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484165

RESUMO

The role of miRNAs in cancer and their possible function as therapeutic agents are interesting and needed further investigation. The miR-26a-5p had been demonstrated as a tumor suppressor in various cancers. However, the importance of miR-26a-5p regulation in upper tract urothelial carcinoma (UTUC) remains unclear. Here, we aimed to explore the miR-26a-5p expression in UTUC tissues and to identify its regulatory targets and signal network involved in UTUC tumorigenesis. The miR-26a-5p expression was validated by quantitative real-time polymerase chain reaction (qPCR) using renal pelvis tissue samples from 22 patients who were diagnosed with UTUC and 64 cases of renal pelvis tissue microarray using in situ hybridization staining. BFTC-909 UTUC cells were used to examine the effects of miR-26a-5p genetic delivery on proliferation, migration and expression of epithelial-to-mesenchymal transition (EMT) markers. MiR-26a-5p was significantly down-regulated in UTUC tumors compared to adjacent normal tissue and was decreased with histological grades. Moreover, restoration of miR-26a-5p showed inhibition effects on proliferation and migration of BFTC-909 cells. In addition, miR-26a-5p delivery regulated the EMT marker expression and inhibited WNT5A/ß-catenin signaling and expression of downstream molecules including NF-κB and MMP-9 in BFTC-909 cells. This study demonstrated that miR-26a-5p restoration may reverse EMT process and regulate WNT5A/ß-catenin signaling in UTUC cells. Further studies warranted to explore the potential roles in biomarkers for diagnostics and prognosis, as well as novel therapeutics targets for UTUC treatment.


Assuntos
Carcinoma de Células de Transição , MicroRNAs , Neoplasias da Bexiga Urinária , Feminino , Humanos , Masculino , MicroRNAs/genética , Transdução de Sinais , Proteína Wnt-5a/genética , beta Catenina
14.
Cell Rep ; 39(1): 110643, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35385754

RESUMO

In this study, we establish a population-based human induced pluripotent stem cell (hiPSC) drug screening platform for toxicity assessment. After recruiting 1,000 healthy donors and screening for high-frequency human leukocyte antigen (HLA) haplotypes, we identify 13 HLA-homozygous "super donors" to represent the population. These "super donors" are also expected to represent at least 477,611,135 of the global population. By differentiating these representative hiPSCs into cardiomyocytes and neurons we show their utility in a high-throughput toxicity screen. To validate hit compounds, we demonstrate dose-dependent toxicity of the hit compounds and assess functional modulation. We also show reproducible in vivo drug toxicity results using mouse models with select hit compounds. This study shows the feasibility of using a population-based hiPSC drug screening platform to assess cytotoxicity, which can be used as an innovative tool to study inter-population differences in drug toxicity and adverse drug reactions in drug discovery applications.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Células-Tronco Pluripotentes Induzidas , Animais , Cardiotoxicidade , Diferenciação Celular , Células Cultivadas , Humanos , Camundongos , Miócitos Cardíacos , Neurônios
15.
Sci Adv ; 8(13): eabm5667, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35363517

RESUMO

CD22 has been suggested to contribute to Alzheimer's disease (AD) pathogenesis by inhibiting microglial amyloid ß (Aß) phagocytosis. Soluble CD22 (sCD22) generated by cleavage from cell membranes may be a marker of inflammation and microglial dysfunction; but alterations of sCD22 levels in AD and their correlation with AD biomarkers remain unclear. Plasma sCD22 levels were measured in cognitively normal non-AD participants and patients with preclinical AD and AD dementia from a Chinese cohort and the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. Plasma sCD22 levels were elevated in patients with preclinical and dementia AD. Plasma sCD22 levels were negatively correlated with cerebrospinal fluid (CSF) Aß42 levels and Aß42/Aß40, and positively correlated with CSF phosphorylated tau levels and brain Aß burden, but negatively correlated with cognitive function. Moreover, higher plasma sCD22 levels were associated with faster cognitive decline during follow-up. These findings suggest that CD22 plays important roles in AD development, and that sCD22 is a potential biomarker for AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Peptídeos beta-Amiloides , Austrália , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Humanos , Fragmentos de Peptídeos , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico
16.
Future Med Chem ; 14(9): 647-663, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35383482

RESUMO

Background: H2S is the third gas transmitter affecting the growth, reproduction and survival of cancer cells. However, the H2S anticancer and antitumor mechanism still needs to be further studied. Methods: Here, FHS-1 was synthesized utilizing excited-state intramolecular proton transfer to detect H2S in MCF-7 cells, and investigated the effects of varying concentrations NaHS on apoptosis. Results: The study found that FHS-1 detects H2S levels with high selectivity and pH stability and that H2S may regulate apoptosis in MCF-7 cells through the p53/mTOR/STAT3 pathway. Conclusion: Researching the influence of H2S on apoptosis can serve as a theoretical foundation for future research into H2S-related anticancer medicines, and the H2S probe can be used as an effective cancer screening tool.


Assuntos
Corantes Fluorescentes , Sulfeto de Hidrogênio , Apoptose , Corantes Fluorescentes/química , Humanos , Células MCF-7 , Prótons
17.
Thorac Cancer ; 13(9): 1419-1422, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35384319

RESUMO

A therapeutic option for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance is a clinical challenge. The clinical outcomes of pembrolizumab in those patients is inconclusive. Cytokine release syndrome (CRS) is a rarely reported immune-related adverse event in the field of immune checkpoint inhibitors therapy, raising challenges given the paucity of data with such presentations. We present the unique case of a 67-year-old female with advanced EGFR-mutated NSCLC who successfully responded to pembrolizumab after EGFR-TKI resistance. However, the patient developed CRS after pembrolizumab initiation and presented with fever, rash, hypotension, hypoxemia, tachycardia, and multiple organ dysfunction. Blood tests showed elevated levels of peripheral CD8+ T cells, C-reactive protein, and tumor necrosis factor-α. The symptoms rapidly improved after corticosteroid initiation. Based on the present case, we propose that pembrolizumab might be a potential salvage therapy for patients with advanced EGFR-mutated NSCLC after EGFR-TKI resistance; CRS would be a sign of the antitumor effect of PD-1 inhibitors in those patients. However, CRS can be a fatal adverse effect and clinicians must remain vigilant for the rare toxicities to make prompt diagnosis and treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Síndrome da Liberação de Citocina , Receptores ErbB/genética , Receptores ErbB/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação , Inibidores de Proteínas Quinases/uso terapêutico
18.
Nanomaterials (Basel) ; 12(7)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35407299

RESUMO

Graphene-based nanocomposite films (NCFs) are in high demand due to their superior photoelectric and thermal properties, but their stability and mechanical properties form a bottleneck. Herein, a facile approach was used to prepare nacre-mimetic NCFs through the non-covalent self-assembly of graphene oxide (GO) and biocompatible proteins. Various characterization techniques were employed to characterize the as-prepared NCFs and to track the interactions between GO and proteins. The conformational changes of various proteins induced by GO determined the film-forming ability of NCFs, and the binding of bull serum albumin (BSA)/hemoglobin (HB) on GO's surface was beneficial for improving the stability of as-prepared NCFs. Compared with the GO film without any additive, the indentation hardness and equivalent elastic modulus could be improved by 50.0% and 68.6% for GO-BSA NCF; and 100% and 87.5% for GO-HB NCF. Our strategy should be facile and effective for fabricating well-designed bio-nanocomposites for universal functional applications.

19.
J Pers Med ; 12(4)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35455732

RESUMO

Metabolic syndrome (MS) has been an important health issue in the world, and insulin resistance (IR) is one of the characteristics of MS, increasing the risk for the onset and poor prognosis of type 2 diabetes mellitus (T2D). However, the interactional effect of obesity or abnormal body composition on the correlation between gut microbiota and IR in T2D patients is not well-explored. This cross-sectional study used a body composition monitor to evaluate lean tissue mass and fat tissue mass. IR was calculated using homeostatic model assessment-insulin resistance (HOMA-IR). Eight pairs of 16S rRNA gene primers specific to Firmicutes, Bacteroidetes, Clostridium leptum group, Faecalibacteriumprausnitzii, B acteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli were utilized to measure their abundance by qPCR. One hundred and fifty-four T2D patients were enrolled and stratified by the median HOMA-IR (2.5) and body mass index (BMI) of 25 kg/m2. A lower abundance of A. muciniphila was found in T2D patients with high HOMA-IR and BMI respectively. HOMA-IR and BMI had a synergistic effect on the reduction of the abundance of A. muciniphila. After adjusting metabolic factors, the low abundance of A. muciniphila significantly increased the risk for greater severity of IR. Furthermore, the negative correlation between A. muciniphila and IR was only found in T2D patients with high lean tissue. In conclusion, decreased abundance of fecal A. muciniphila enhanced the severity of IR in Asians with T2D, especially those having lean mass, and this significant relationship was independent of obesity.

20.
Hypertens Pregnancy ; 41(2): 126-138, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35361052

RESUMO

OBJECTIVES: This network meta-analysis aimed to compare the efficacy and safety of intravenous (IV) hydralazine, oral nifedipine, and IV labetalol with different dosage regimens in the treatment of severe hypertension during pregnancy. METHODS: A comprehensive literature search was performed on PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) exploring the effects of hydralazine, nifedipine, and labetalol in the treatment of severe hypertension during pregnancy. RESULTS: A total of 21 RCTs with 2183 patients comparing 7 regimens (oral nifedipine 50,60,90 mg; hydralazine 15,25 mg; and labetalol 220,300 mg) were identified. Compared with IV labetalol 300 mg, nifedipine 50,60, and 90 mg significantly improved the successful treatment rate of severe hypertension during pregnancy, nifedipine 50 and 90 mg and IV hydralazine 25 mg required significantly fewer doses to achieve target blood pressure (BP), and nifedipine 50 mg took significantly shorter time to achieve target BP. Subgroup analysis showed that only nifedipine 50 mg tablets, not capsules, required a significantly shorter time and fewer doses to achieve target BP than IV labetalol 300 mg. Moreover, nifedipine 60,90 mg showed superior effectiveness than IV hydralazine 15,25 mg in the successful treatment rate of severe hypertension during pregnancy. SUCRA analysis suggested that nifedipine 50,60,90 mg as the better regimens with the lower rates of overall ADR and neonatal complications. CONCLUSION: These findings demonstrated the superiority of oral nifedipine 50,60,90 mg, especially oral nifedipine 50 mg tablets, in the treatment of severe hypertension during pregnancy than IV labetalol 300 mg, while oral nifedipine 60,90 mg also showed superiority in the successful treatment rate of severe hypertension during pregnancy than IV hydralazine 15,25 mg. However, the limitations of the underlying data indicate that future large-scale and rigorous RCTs are needed to confirm such findings.


Assuntos
Hipertensão Induzida pela Gravidez , Hipertensão , Labetalol , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Feminino , Humanos , Hidralazina/farmacologia , Hidralazina/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Recém-Nascido , Labetalol/efeitos adversos , Metanálise em Rede , Nifedipino/farmacologia , Nifedipino/uso terapêutico , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
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