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1.
J Hazard Mater ; 470: 134219, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38615647

RESUMO

Disposable surgical masks undeniably provide important personal protection in daily life, but the potential health risks by the release of microplastic fibres from masks should command greater attention. In this study, we conducted a microplastic fibre release simulation experiment by carrying masks in a pocket and reusing them, to reveal the number and morphological changes of microfibres released. Fourier transform infrared spectrometry, scanning electron microscopy, and optical microscopy were employed to analyse the physical and chemical characteristics of the mask fibres. The results indicated that the reuse of disposable masks led to a significant release of microplastic fibres, potentially leading to their migration into the respiratory system. Furthermore, the release of microplastic fibres increased with prolonged external friction, particularly when masks were stored in pockets. The large-scale release of microplastic fibres due to mask reuse raises concerns about potential health risks to the human respiratory system. The reuse of disposable masks should be also strictly avoided in daily life in the future. Furthermore, the current study also established a robust foundation for future research endeavours on health risks associated with microplastic fibres entering the respiratory system through improper mask usage.

2.
Environ Res ; 251(Pt 2): 118677, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38508358

RESUMO

Recent studies demonstrated that plastic degradation in Zophobas atratus superworms is related to the gut microbiota. To determine whether the biodegradation and gut-microbiota were influenced by ingested plastic polymerization types, foams of polypropylene (PP), polyurethane (PU) and ethylene vinyl acetate (EVA) were selected as representatives of polyolefins, polyester and copolymers, and the sole feedstock for superworms for 45 d. Both growth and survival rates of superworms were influenced by the type of plastic diet. Although the total consumptions of EVA- and PP-fed groups were similar at 29.03 ± 0.93 and 28.89 ± 1.14 mg/g-larva, which were both significantly higher than that of PU-fed groups (21.63 ± 2.18 mg/g-larva), the final survival rates of the EVA-fed group of 36.67 ± 10.41% exhibited significantly lower than that of the PP- and PU-fed groups of 76.67 ± 2.89% and 75.00 ± 7.07%, respectively, and even the starvation group of 51.67 ± 10.93%. The Illumina MiSeq results revealed similarities in the dominant gut bacterial communities between PU- and EVA-fed groups, with an increase in relative abundance of Lactococcus, but significant differences from the PP-fed groups, which had two predominant genera of unclassified Enterobacteriaceae and Enterococcus. Compared to bran-fed groups, changes in gut fungal communities were similar across all plastics-fed groups, with an increase in the dominant abundance of Rhodotorula. The abundance of Rhodotorula increased in the order of polyolefin, polyester, and copolymer. In summary, plastic ingestion, larval growth, and changes in gut bacterial and fungal community of superworms were all influenced by foam diets of different polymerization types, and especially influences on the gut microbiomes were different from each other.

3.
Cancer Lett ; 588: 216734, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38401886

RESUMO

Telomerase activity is upregulated in head and neck squamous cell carcinoma (HNSCC), yet its regulatory mechanisms remain unclear. Here, we identified a cancer-specific lncRNA (LINC02454) associated with poor prognosis by using LncRNA chip of our HNSCC cohorts and external datasets. Through employing negative-stain transmission electron microscopy (NS-TEM), we discovered an interaction between LINC02454 and CCT complex which would augment telomerase activity for maintaining telomere homeostasis. Supporting this, in the telomerase repeat amplification protocol (TRAP) assay and quantitative fluorescence in situ hybridization (Q-FISH) analysis, LINC02454 depletion significantly reduced telomerase activity and shortened telomere length. Consistently, pathways related to telomerase, mitosis, and apoptosis were significantly impacted upon LINC02454 knockdown in RNAseq analysis. Functionally, LINC02454-deficient cells exhibited a more significant senescence phenotype in ß-galactosidase staining, cell cycle, and apoptosis assays. We further confirmed the role of LINC02454 in HNSCC proliferation through a combination of in vitro and in vivo experiments. The therapeutic potential of targeting LINC02454 was verified by adenovirus-shRNA approach in HNSCC patient-derived xenograft (PDX) models. In summary, our findings provided valuable insights into the molecular mechanisms of HNSCC tumorigenesis and potential targets for future treatment modalities.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , RNA Longo não Codificante , Telomerase , Humanos , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Hibridização in Situ Fluorescente , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Telomerase/genética , Telomerase/metabolismo , Telômero/genética , Telômero/metabolismo , Encurtamento do Telômero
4.
BMJ Open ; 14(2): e074541, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341200

RESUMO

OBJECTIVES: Anthracycline-induced cardiotoxicity is a debilitating cardiac dysfunction for which there are no effective treatments, making early prevention of anthracycline-induced subclinical cardiotoxicity (AISC) crucial. High-density lipoprotein cholesterol (HDL-C) plays a role in cardioprotection, but its impact on AISC remains unclear. Our study aims to elucidate the protective capacity of HDL-C in AISC in patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone and rituximab). DESIGN: Prospective observational study. SETTING: Conducted in China from September 2020 to September 2022. PARTICIPANTS: 70 chemotherapy-naïve patients newly diagnosed with DLBCL who were scheduled to receive the standard dose of R-CHOP; 60 participants included in a case-control study (DOI: 10.1186/s12885-022-10085-6). PRIMARY OUTCOME MEASURES: Serum biomarkers, 2D speckle tracking echocardiography and conventional echocardiography were measured at baseline, at the end of the third and sixth cycles of R-CHOP and 6 and 12 months after chemotherapy. RESULTS: 24 patients experienced AISC, while 10 did not. 36 patients were lost to follow-up and death. Cox regression analysis showed that higher levels of HDL-C were associated with a significantly lower risk of AISC (unadjusted HR=0.24, 95% CI 0.09 to 0.67, p=0.006; adjusted HR=0.27, 95% CI 0.09 to 0.79, p=0.017). Patients without AISC had a more stable and higher HDL-C level during the follow-up period. HDL-C levels significantly decreased from the end of the third cycle of chemotherapy to the end of the sixth cycle of chemotherapy in all patients (p=0.034), and particularly in the AISC group (p=0.003). The highest level of HDL-C was significantly higher in patients without AISC than in those with AISC (1.52±0.49 vs 1.22±0.29, p=0.034). CONCLUSIONS: Our study suggests that higher HDL-C levels may associate with lower AISC risk in patients with DLBCL treated with R-CHOP. HDL-C could be a cardioprotective target, but further research is needed to confirm its benefits and limitations. STUDY REGISTRATION NUMBER: Study registration number: ChiCTR2100054721.


Assuntos
Antraciclinas , Cardiotoxicidade , HDL-Colesterol , Linfoma Difuso de Grandes Células B , Humanos , Antraciclinas/toxicidade , Antibióticos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azidas , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Estudos de Casos e Controles , Ciclofosfamida/uso terapêutico , Cimarina/análogos & derivados , Doxorrubicina/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Vincristina/uso terapêutico
5.
BMC Cancer ; 23(1): 976, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37833648

RESUMO

BACKGROUND: Current treatment of acute leukemia is based on anthracycline chemotherapy. Anthracyclines, despite improving patient survival, have serious cardiotoxicity and therefore cardiac monitoring should be a priority. The purpose of this study is to explore the possible early predictors of anthracycline-induced subclinical cardiotoxicity(AISC)in acute leukemia patients. METHODS: We conducted a prospective observational study involving 51 patients with acute leukemia treated with anthracycline. Demographic data, clinical variables, echocardiography variables and biochemical variables were collected at baseline and after 3 cycles of chemotherapy. Patients were divided into the AISC and No-AISC groups according to changes of global longitudinal peak systolic strain. Regression models and receiver operating characteristic curve analysis were used to explore the relationship between the variables and AISC. RESULT: 17 of the patients suffered subclinical cardiotoxicity after 3 cycles of anthracycline treatment. Multiple logistic regression analysis showed a significant association of DBil (OR 0.612, 95% CI 0.409-0.916, p = 0.017), TBil (OR 0.841, 95% CI 0.717-0.986, p = 0.033), PLT (OR 1.012, 95% CI 1.002-1.021, p = 0.016) and Glu (OR 1.873, 95% CI 1.009-3.475, p = 0.047) with the development of AISC. After 3 cycles of chemotherapy, there was a significant difference in PLT between the AISC and NO-AISC groups. Moreover, the dynamic changes in PLT from baseline to after 3 cycles of chemotherapy were each statistically significant in the AISC and NO-AISC groups. The combination of PLT and N-terminal pro-B-type natriuretic peptide (NT-proBNP) had the highest area under curves (AUC) for the diagnosis of AISC than PLT and NT-proBNP alone (AUC = 0.713, 95%CI: 0.56-0.87, P = 0.017). CONCLUSION: Total bilirubin (TBil), direct bilirubin (DBil), platelets (PLT) and blood glucose (Glu) are independent influencing factors for AISC in acute leukemia patients receiving anthracycline therapy. Bilirubin may be a protective factor and PLT may be a contributing factor for AISC. The combination of baseline PLT and baseline NT-proBNP shows satisfactory predictive ability for AISC in acute leukemia cases treated with 3 cycles of chemotherapy.


Assuntos
Antraciclinas , Leucemia Mieloide Aguda , Humanos , Doença Aguda , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Bilirrubina , Biomarcadores , Cardiotoxicidade/etiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Estudos Prospectivos
6.
Sci Total Environ ; 904: 166808, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37683868

RESUMO

During the COVID-19 pandemic, the usage and production of face masks considerably increased, resulting in large quantities of mask waste accumulating in the natural environment. To investigate whether masks of polypropylene (PP) material could be ingested and degraded by insect worms like PP foam plastic, yellow mealworms were provided with different layers of disposable surgical masks as sole diets for 30 d. Although mask layers, especially the middle layer of melt-blown filter, could be ingested by yellow mealworms, sole mask layer diets had adverse effects on the larval survival and growth. Analyses of Fourier transform infrared spectroscopy, differential scanning calorimeter and thermogravimetric, and gel permeation chromatography demonstrated the changes of functional groups, thermostability and molecular weights in frass compared to original masks, indicating the partial oxidation and degradation of masks. And the depolymerization of the middle layer of masks by yellow mealworms was different from that of other layers. The larval gut bacterial and fungal microbiomes were assessed by Illumina MiSeq, indicating that both of them shifted upon sole layer mask diets. Changes in relative abundances of dominant bacterial and fungal genera demonstrated the strong association between gut microbiome and mask degradation. For instance, unclassified Enterobacteriaceae was closely associated with outer layers degradation. Lactococcus and unclassified Ascomycota were responsible for middle layers degradation, while Lactococcus and Morganella for inner layers degradation. In conclusion, disposable surgical masks of PP material could be ingested and biodegraded by yellow mealworms. The diversities of gut bacterial and fungal microbiomes were associated with the differences in rigid crystalline structures of the layer masks.


Assuntos
Microbioma Gastrointestinal , Tenebrio , Animais , Humanos , Larva , Tenebrio/metabolismo , Poliestirenos/metabolismo , Máscaras , Pandemias , Bactérias/metabolismo , Polipropilenos , Ingestão de Alimentos , Plásticos/metabolismo
7.
Exp Ther Med ; 25(3): 142, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36845950

RESUMO

Phase angle (PhA), as measured by bioelectrical impedance analysis, is an important parameter in nutritional assessment and is highly predictive of clinical outcomes in various diseases; however, there is little research on its use in acute myeloid leukemia (AML). Therefore, the present study was conducted to determine the association between PhA and malnutrition and to clarify the prognostic significance of PhA for progression-free survival (PFS) and overall survival (OS) in adult patients with AML (excluding acute promyelocytic leukemia) who were undergoing chemotherapy. A total of 70 patients with newly diagnosed AML were enrolled. After chemotherapy, the nutritional risk for patients with a reduced baseline PhA increased significantly. Disease progression occurred in 28 patients, of which 23 died, with a median follow-up of 9.3 months. A reduced baseline PhA was associated with poor PFS (7.1 months vs. 11.6 months; P=0.001) and OS (8.2 months vs. 12.1 months; P=0.011). A multivariate analysis revealed that a reduced PhA was an independent risk factor for disease progression (hazard ratio, 3.13; 95% CI, 1.21-8.11; P=0.019). Overall, these results suggested that PhA is an effective and sensitive indicator that may provide important nutritional and prognostic information in patients with AML.

8.
Int J Gen Med ; 15: 8603-8615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36545244

RESUMO

Objective: In the direction of evaluating the current status of outcome indicators and control group selection in randomized controlled studies of Chinese herbal compounding (such as Sini plus Renshen Decoction, Jianpifuzhengfang, Bufei Jianzhong Decoction, etc) for cancer-caused fatigue and to provide a reference for clinical studies of Chinese herbal compounding for cancer-caused fatigue. Methods: Randomized controlled studies of Chinese herbal medicine for cancer-caused fatigue in the midst of 2012 and 2022 were searched in CNKI, PubMed, and EMBASE databases on the China Knowledge Network, and the literature was screened using NoteExpress. Two researchers independently conducted the literature review, and then the studies that met the criteria were grouped and analyzed adopting qualitative analysis of outcome indicators and control groups. Results: A total of 70 randomized controlled studies that met the requirements were included, and after doing statistical analysis, it can draw to the conclusion that the risk of bias in the included studies was high; at the same time, the TCM evidence score scale, objective indicators, and safety indicators were underutilized; additionally, there were no uniform standards for the fatigue scale, and the selection of control groups lacked balance and consistency. Conclusion: The outcome indicators of TCM compound treatment of cancer-caused fatigue should be on the basis of the principle of "diagnosis and treatment" in TCM, the proportion of objective indicators should be exaggerated, as well as the interventions in the control group should be unified.

9.
Sci Rep ; 12(1): 18994, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348051

RESUMO

Site-selectively chemical bioconjugation of peptides and proteins can improve the therapeutic exploration of modified protein drugs. Only 3.8% natural abundance of phenylalanine in protein and nearly 90% of proteins contain at least one phenylalanine residue in their sequenced, showing the potential in biopharmaceutical utility of the phenylalanine bioconjugation. However, the covalent bioconjugation of native phenylalanine is one of the most challenging problems in protein modification. Herein, an approach to protein modification is described that relies on a photoredox method for the site-selective bioconjugation of phenylalanine. This methodology has been validated on peptides as well as protein insulin using a straightforward and mild condition. In addition, based on characterization by near-UV CD spectroscopy and small angle X-ray scattering (SAXS), this pyrazole labeling approach permitted the insulin hexamer to completely dissociate into the monomeric form, thus making it a potential candidate for use as rapid-acting insulin for the treatment of diabetes.


Assuntos
Fenilalanina , Proteínas , Fenilalanina/química , Espalhamento a Baixo Ângulo , Difração de Raios X , Proteínas/química , Peptídeos/química , Insulina/química
10.
Front Cell Infect Microbiol ; 12: 987683, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36250046

RESUMO

Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial peptidyl arginine deiminase. Gingipain R cleaves host proteins to expose the C-terminal arginines for peptidyl arginine deiminase to citrullinate and generate citrullinated proteins. Apart from carrying out citrullination in the periodontium, the bacterium is found capable of citrullinating proteins present in the host synovial tissues, atherosclerotic plaques and neurons. Studies have suggested that both virulence factors are the key factors that trigger distal effects mediated by citrullination, leading to the development of some non-communicable diseases, such as rheumatoid arthritis, atherosclerosis, and Alzheimer's disease. Thus, inhibition of these virulence factors not only can mitigate periodontitis, but also can provide new therapeutic solutions for systematic diseases involving bacterial citrullination. Herein, we described both these proteins in terms of their unique structural conformations and biological relevance to different human diseases. Moreover, investigations of inhibitory actions on the enzymes are also enumerated. New approaches for identifying inhibitors for peptidyl arginine deiminase through drug repurposing and virtual screening are also discussed.


Assuntos
Periodontite , Porphyromonas gingivalis , Cisteína Endopeptidases Gingipaínas , Humanos , Hidrolases , Periodontite/microbiologia , Desiminases de Arginina em Proteínas/metabolismo , Fatores de Virulência
11.
World J Clin Cases ; 10(27): 9703-9713, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36186177

RESUMO

BACKGROUND: Gemcitabine plus nab-paclitaxel (GA) is a commonly used first-line treatment regimen for metastatic pancreatic cancer, and many studies will add a novel targeted agent to this regimen for improving patient survival rate. However, the clinical effectiveness of GA is the most controversial issue. AIM: To compare the efficacy and safety of GA regimen with a targeted agent and GA regimen. METHODS: Up to 1 December 2021, the eligible randomized controlled trials (RCTs) relating to GA and GA with a targeted agent were searched on PubMed, EMBASE and Cochrane Library for eligible data. We screened out appropriate studies for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and toxicity, which had been pooled and finally analyzed by using Stata version 15.1. In addition, we use Reference Citation Analysis (https://www.referencecitationanalysis.com/) to collect the latest related literature to improve the latest cutting-edge research results. RESULTS: Seven RCTs involving 1544 patients (848 men and 696 women) were included. There were no significant differences between GA with a targeted agent and GA in PFS [hazard ratio (HR): 1.18 95% confidence interval (CI): 0.91-1.53], OS (HR: 1.12 95%CI: 0.99-1.27), and ORR (HR: 0.96 95%CI: 0.71-1.29). There was no notable difference in the two groups in grade 3/4 toxicity (fatigue, anemia, vomiting and neutropenia), whereas the incidence of grade 3/4 diarrhea considerably increased in GA with a targeted drug. CONCLUSION: Adding a novel targeted agent to the GA regimen did not improve survival rate of patients with metastatic pancreatic cancer.

12.
BMC Cancer ; 22(1): 988, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115970

RESUMO

BACKGROUND: Anthracycline-induced cardiotoxicity is an irreversible cardiac cell injury. Therefore, it's very important to identify influencing factors of anthracycline-induced subclinical cardiotoxicity (AISC). This study was designed to analyze the influencing factors of AISC in patients with diffuse large B-cell lymphoma (DLBCL) treated with the (R)-CHOP chemotherapy regimen. METHODS: This is an ongoing observational prospective clinical trial. All patients underwent conventional echocardiography and speckle tracking echocardiography at the time of enrollment and during treatment. Changes of global longitudinal peak systolic strain were assessed after 3 cycles of (R)-CHOP chemotherapy, and patients were divided into the AISC and No-AISC groups. Demographic data, clinical variables, and biochemical variables were measured. Regression models, receiver operating characteristic curve analysis, and difference values were used to explore the relationships between variables and AISC. RESULTS: Among 70 patients who completed 3 cycles of (R)-CHOP chemotherapy, 26 developed AISC. In multiple logistic regression, HDL-C (P = 0.047), ApoA1 (P = 0.022), TG (P = 0.029) and e' (P = 0.008) were associated with AISC. The combination of HDL-C and NT-proBNP had the highest area under curves (AUC) for the diagnosis of AISC than HDL-C and NT-proBNP alone (AUC = 0.752, 95%CI: 0.63-0.87, P = 0.001). Between the No-AISC and AISC groups, there was no significant difference in HDL-C, ApoA1, and e' at baseline and after 3 cycles of chemotherapy, respectively. The dynamic changes of HDL-C, ApoA1, and e' from baseline to the end of the 3rd cycle of chemotherapy showed statistically significant differences. CONCLUSIONS: HDL-C, ApoA1, TG, and e' are independent predictive factors in DLBCL cases treated with the (R)-CHOP chemotherapy regimen. The combination of HDL-C and NT-proBNP may improve the predictive ability for AISC in patients with DLBCL administered 3 cycles of (R)-CHOP chemotherapy. Dynamic changes of HDL-C, ApoA1, and e' may be meaningful for predicting AISC. TRIAL REGISTRATION: Our study was registered in the Chinese Clinical Trial Registry (Approval ID. ChiCTR2100054721 http://www.chictr.org.cn/showproj.aspx?proj=145082 ).


Assuntos
Antraciclinas , Linfoma Difuso de Grandes Células B , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Estudos Prospectivos
13.
Sci Total Environ ; 839: 156289, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35644389

RESUMO

The discovery that insect larvae can feed on foam plastics provided new exploration ideas and potential for plastic wastes biodegradation. In previous studies, both attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR) and conventional FT-IR have been used but no comparison has been done to evaluate the difference of effectiveness for the characterization of oxidization and biodegradation of plastics by insect larvae. To address this, foam plastics of polystyrene, polyurethane and polyethylene, as well as the frass of plastics-fed superworms Zophobas atratus were characterized using both FT-IR and ATR-FT-IR, and the differences were compared. For FT-IR, spectra were found to vary due to the difference in shape and thickness of the samples, as well as the moisture absorption of KBr. For ATR-FT-IR, although tests could be performed directly without pretreatment, the reflection with short wavelength could not deeply penetrate into the frass samples. Since the composition of plastics-fed larval frass is more complex than the original plastics, the spectra of FT-IR and ATR-FT-IR were observed significantly different. Therefore, the ATR-FT-IR was more effective in monitoring functional groups of original plastics, and be recommended to employ in combination with FT-IR for a more comprehensive characterization of plastics-fed larval frass in future studies.


Assuntos
Besouros , Plásticos , Animais , Análise de Fourier , Larva , Plásticos/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
14.
Chem Sci ; 13(8): 2310-2316, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35310496

RESUMO

A paired electrolysis enabled cascade annulation that enables the efficient synthesis of highly functionalized quinoline-substituted bioactive molecules from readily available starting materials is reported. Using this methodology, two goals, namely, the direct synthesis of quinolines and the introduction of quinoline moieties to bioactive molecules, can be simultaneously achieved in one simple operation. The use of electroreduction for the activation of isatin, together with the further anodic oxidation of KI to catalytically result in a cascade annulation, highlight the unique possibilities associated with electrochemical activation methods. This transformation can tolerate a wide range of functional groups and can also be used as a functionalization tactic in pharmaceutical research as well as other areas.

15.
Int J Gen Med ; 15: 1261-1269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35173465

RESUMO

BACKGROUND: We aimed to explore the potential association of body composition parameters measured by bioelectrical impedance analysis (BIA) with the incidence of sarcopenia in patients with acute myeloid leukemia (AML) (non-M3) after chemotherapy. PATIENTS AND METHODS: This was a single-center observational study. Sixty-nine patients with newly diagnosed AML underwent BIA at the time of initial diagnosis and after completion of three chemotherapy sessions. Pre- and post-chemotherapy BIA parameters were compared. Sarcopenia was defined as low skeletal muscle mass plus low muscle strength according to the Asian Working Group for Sarcopenia (AWGS). Association of sarcopenia with mid-arm muscle circumference (MAMC) and intracellular water (ICW) was assessed by multivariate logistic regression. RESULTS: There was a significant increase in the prevalence of sarcopenia after chemotherapy (39.1% vs 14.5%, P<0.001). Skeletal muscle mass (SMM), fat-free mass (FFM), and soft lean mass (SLM) showed a significant decrease after chemotherapy (P<0.05). MAMC, ICW, and total body water (TBW) significantly decreased after chemotherapy (P<0.05). BIA indices including appendicular skeletal muscle mass (ASM) (r=0.889, P<0.001), ICW (r=0.869, P<0.001), MAMC (r=0.849, P<0.001) showed a positive correlation with SMI. Moreover, ASM (r=-0.453 P=0.001), ICW (r=-0.322, P<0.05), and MAMC (r=-0.352, P<0.05) showed a negative correlation with sarcopenia. On multivariate logistic regression analysis, increased ICW was associated with decreased risk of sarcopenia [odds ratio (OR): 0.50; 95% confidence interval (CI) 0.30-0.82]. Each additional unit of MAMC after chemotherapy was associated with 71% lower risk of sarcopenia (OR: 0.29; 95% CI 0.13-0.66). CONCLUSION: The incidence of sarcopenia was associated with chemotherapy of patients with AML (non-M3) as reflected by body composition changes.

16.
Org Lett ; 23(7): 2710-2714, 2021 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-33749289

RESUMO

The late-stage functionalization of N-unprotected indoles can be useful for modifying low-molecular-weight drugs and bioactive peptides. Whereas indole carboxamides are valuable in pharmaceutical applications, the preparation N-(indol-2-yl)amides with similar structures continues to be challenging. Herein we report on visible-light-induced late-stage photoredox C-H amidation with N-unprotected indoles and tryptophan-containing peptides, leading to the formation of N-(indol-2-yl)amide derivatives. N-Unprotected indoles and aryloxyamides that contain an electron-withdrawing group could be coupled directly to eosin Y as the photocatalyst by irradiation with a green light-emitting diode at room temperature. Mechanistic studies and density functional theory calculations indicate that the transformation might proceed through the oxidative C-H functionalization of indole with a PS* to PS•- cycle. This protocol provides a new toolkit for the late-stage modification labeling and peptide-drug conjugation of N-unprotected indole derivatives.

17.
Clin Chim Acta ; 506: 172-175, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32229107

RESUMO

We report the dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a COVID-19 patient: from successive negative results to successive single positive nucleocapsid gene, to two positive target genes (orf1ab and nucleocapsid) by RT-PCR testing of SARS-Cov-2, and describe the diagnosis, clinical course, and management of the case. In this case, negative results of RT-PCR testing was not excluded to diagnose a suspected COVID-19 patient, clinical signs and symptoms, other laboratory findings, and chest CT images should be taken into account for the absence of enough positive evidence. This case highlights the importance of successive sampling and testing SARS-Cov-2 by RT-PCR as well as the increased value of single positive target gene from pending to positive in two specimens to diagnose laboratory-confirmed COVID-19.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , COVID-19 , China , Infecções por Coronavirus/fisiopatologia , Proteínas do Nucleocapsídeo de Coronavírus , Progressão da Doença , Perfilação da Expressão Gênica , Regulação Viral da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo/genética , Pandemias , Fosfoproteínas , Pneumonia Viral/fisiopatologia , Poliproteínas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Proteínas Virais/genética
18.
Angew Chem Int Ed Engl ; 59(18): 7193-7197, 2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-32073715

RESUMO

Dearomative annulation of indoles has emerged as a powerful tool for the preparation of polycyclic indoline-based alkaloids. Compared with well-established methods towards five-membered-ring-fused indolines, the six-membered-ring-fused indolines are rarely accessed under thermal conditions. Herein, a dearomative [4+2] annulation between different indoles is developed through an electrochemical pathway. This transformation offers a remarkably regio- and stereoselective route to highly functionalized pyrimido[5,4-b]indoles under oxidant- and metal-free conditions. Notably, this electrochemical approach maintains excellent functional-group tolerance and can be extended as a modification tactic for pharmaceutical research. Preliminary mechanism studies indicate that the electrooxidation annulation proceeds through radical-radical cross-coupling between an indole radical cation and an N-centered radical generated in situ.


Assuntos
Alcaloides/síntese química , Técnicas Eletroquímicas , Indóis/química , Alcaloides/química , Radicais Livres/síntese química , Radicais Livres/química , Hidrogenação , Estrutura Molecular , Oxirredução
19.
Commun Chem ; 3(1): 171, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36703459

RESUMO

Bioconjugation reactions play a central facilitating role in engendering modified peptides and proteins. Early progress in this area was inhibited by challenges such as the limited range of substrates and the relatively poor biocompatibility of bioconjugation reagents. However, the recent developments in visible-light induced photoredox catalysis and electrochemical catalysis reactions have permitted significant novel reactivities to be developed in the field of synthetic and bioconjugation chemistry. This perspective describes recent advances in the use of biocompatible energy input for the modification of peptides and proteins mainly, via the single electron transfer (SET) process, as well as key future developments in this area.

20.
Chem Sci ; 10(34): 7982-7987, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31673320

RESUMO

Directly introducing a beneficial functional group into biomolecules under mild, clean and easy-to-handle conditions is of great importance in the field of chemical biology and pharmacology. Herein, we described an electrochemical strategy to perform the bioconjugation of tyrosine residues with phenothiazine derivatives in a rapid and simple manner. In this electrochemical system, various polypeptides and proteins were successfully labelled with excellent site- and chemo-selectivity, and metals, oxidants or additives were also avoided.

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