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1.
Heliyon ; 10(7): e28251, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596099

RESUMO

Objectives: Small cell lung cancer (SCLC) shows poor prognosis since it metastasizes widely at early stage. Paired box gene (PAX) 8 is a transcriptional factor of PAX family, of which the expression in lung cancer is a controversial issue, and its prognostic value of PAX8 in SCLC is still unclear. Materials and methods: Overall, 184 subjects who were pathologically diagnosed with SCLC were enrolled in the study. Immunohistochemical analysis of PAX8 and Ki-67 were performed. The correlations between PAX8 expression and clinical features or Ki-67 index were further analyzed. Subsequently, an analysis of the association between PAX8, stage, Ki-67 status, and overall survival (OS) were performed in 169 subjects with follow-up information. Results: PAX8 was positive in 53.8% (99/184) SCLC specimens. The positive rate is significantly higher in extensive-stage specimens (61.0%) than in limited-stage specimens (45.24%). PAX8 expression is positively correlated with Ki-67 index (P = 0.001) while negatively correlated with OS (HR = 3.725, 95% CI 1.943-7.139, P<0.001). In combination groups, the PAX8 negative and limited stage group had the most promising OS. Conclusion: PAX8 expression rate in SCLC specimens is not low. It has prognostic value in small cell lung cancer.

2.
Sci Rep ; 14(1): 8400, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600140

RESUMO

Due to the increased frequency of extreme weather events and the implementation of the China's dual-carbon target, thermal power companies have been under pressure to construct green infrastructure and to actively pursue low-carbon transformation in response to stricter environmental regulations. This research thus selects 30 listed thermal power enterprises in China as study objects and assesses their green investment efficiency in the low-carbon transition process using three-stage DEA evaluation model with environmental regulation as an exogenous variable. Based on this, a benchmark regression model is used to corroborate the relationship between environmental regulation and green investment. Simultaneously, we carry out analysis to compare the correlation between thermal power firms' green investment efficiency and their focus on green investments. The results show in terms of total efficiency that environmental regulation significantly improves the total efficiency of 80% of thermal power enterprises compared to the absence of this exogenous variable. With the addition of environmental regulation, firms' total efficiency declines gradually in general from 2018 to 2022, with the mean value of efficiency falling by 0.068. In terms of stage-specific efficiency, the efficiency of the green investment stage of the majority of firms is between 0.3 and 0.6, which is much lower than that of the operational stage and the market performance stage. In terms of sub-indicator efficiency, both green investment efficiency and social donation efficiency among thermal power enterprises show obvious polarization, with 30% of them having an efficiency of 1 and 30% less than 0.1. In terms of green investment focus, thermal power unit renovation has a more obvious role in boosting the green investment efficiency of thermal power enterprises than do wind power and photovoltaic projects. Therefore, both governmental departments and thermal power enterprises need to take active measures in order to achieve green transformation from the perspective of green investment efficiency. Through the segmentation of important projects of green investment, this paper provides a reasonable investment direction reference for the sustainable transformation of China's thermal power industry. It also provides a rich and novel theoretical basis for the Chinese government to further improve the relevant environmental protection laws and regulations of thermal power industry.

3.
Int J Stroke ; : 17474930241252530, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651756

RESUMO

BACKGROUND: Post-stroke cognitive impairment (PSCI) occurs in up to 50% of stroke survivors. Presence of pre-existing vascular brain injury, in particular the extent of white matter hyperintensities (WMH), is associated with worse cognitive outcome after stroke, but the role of WMH location in this association is unclear. AIM: We determined if WMH in strategic white matter tracts explain cognitive performance after stroke. METHODS: Individual patient data from 9 ischemic stroke cohorts with MRI were harmonized through the Meta VCI Map consortium. The association between WMH volumes in strategic tracts and domain-specific cognitive functioning (attention and executive functioning, information processing speed, language and verbal memory) was assessed using linear mixed models and lasso regression. We used a hypothesis-driven design, primarily addressing four white matter tracts known to be strategic in memory clinic patients: the left and right anterior thalamic radiation, forceps major and left inferior fronto-occipital fasciculus. RESULTS: The total study sample consisted of 1568 patients (39.9% female, mean age: 67.3 years). Total WMH volume was strongly related to cognitive performance on all four cognitive domains. WMH volume in the left anterior thalamic radiation was significantly associated with cognitive performance on attention and executive functioning and information processing speed, and WMH volume in the forceps major with information processing speed. The multivariable lasso regression showed that these associations were independent of age, sex, education, and total infarct volume and had larger coefficients than total WMH volume. CONCLUSIONS: These results show tract-specific relations between WMH volume and cognitive performance after ischemic stroke, independent of total WMH volume. This implies that the concept of strategic lesions in PSCI extends beyond acute infarcts and also involves pre-existing WMH. DATA AVAILABILITY: The Meta VCI Map consortium is dedicated to data sharing, following our guidelines.

4.
Heliyon ; 10(7): e28755, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586372

RESUMO

Fish mint, Houttuynia cordata Thunb. (HCT) is an edible vegetable that has also been used in traditional folk medicines. As both a medicinal herb and a dietary source, HCT has been clinically proven to be a pivotal ingredient in formulas administered to alleviate COVID-19 symptoms. With the increasing market demand for imported materials, ensuring the quality consistency of HCT becomes a significant concern. In this study, the growing time for hydroponically-cultivated HCT with seaweed extract and amino acids added (HCTW) reduced by half compared to conventional soil-cultivated HCT (HCTS). Key quantified components in HCTW, flavonoid glycosides and caffeoylquinic acid derivatives, exhibited a 143% increase over HCTS. These crucial constituents were responsible for possessing antioxidant activity (IC50 < 25 µg/mL) and anti-nitrite oxide production (IC50 < 20 µg/mL). An economically-designed hydroponic system with appropriate additives is proposed to replace HCTS with improvements of growth time, overall production yields, and bioactive qualities.

5.
PLoS One ; 19(4): e0300626, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38573998

RESUMO

BACKGROUND: Cuproptosis is a recently discovered type of cell death, but the role and behavior of cuproptosis-related genes (CuRGs) in cancers remain unclear. This paper aims to address these issues by analyzing the multi-omics characteristics of cancer-related genes (CuRGs) across various types of cancer. METHOD: To investigate the impact of somatic copy number alterations (SCNA) and DNA methylation on CRG expression, we will analyze the correlation between these factors. We developed a cuproptosis index (CPI) model to measure the level of cuproptosis and investigate its functional roles. Using this model, we assessed the clinical prognosis of colorectal cancer patients and analyzed genetic changes and immune infiltration features in different CPI levels. RESULTS: The study's findings indicate that the majority of cancer-related genes (CuRGs) were suppressed in tumors and had a positive correlation with somatic copy number alterations (SCNA), while having a negative correlation with DNA methylation. This suggests that both SCNA and DNA methylation have an impact on the expression of CuRGs. The CPI model is a reliable predictor of survival outcomes in patients with colorectal cancer and can serve as an independent prognostic factor. Patients with a higher CPI have a worse prognosis. We conducted a deeper analysis of the genetic alterations and immune infiltration patterns in both CPI positive and negative groups. Our findings revealed significant differences, indicating that CuRGs may play a crucial role in tumor immunity mechanisms. Additionally, we have noticed a positive correlation between CuRGs and various crucial pathways that are linked to the occurrence, progression, and metastasis of tumors. CONCLUSIONS: Overall, our study systematically analyzes cuproptosis and its regulatory genes, emphasizing the potential of using cuproptosis as a basis for cancer therapy.


Assuntos
Neoplasias Colorretais , Oncogenes , Humanos , Análise de Sistemas , Morte Celular , Metilação de DNA , Neoplasias Colorretais/genética , Apoptose , Cobre
6.
Org Biomol Chem ; 22(13): 2620-2629, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38451121

RESUMO

Mechanochemical reactions achieved by processes such as milling and grinding are promising alternatives to traditional solution-based chemistry. This approach not only eliminates the need for large amounts of solvents, thereby reducing waste generation, but also finds applications in chemical and materials synthesis. The focus of this study is on the synthesis of quinazolinone derivatives by ball milling, in particular evodiamine and rutaecarpine analogues. These compounds are of interest due to their diverse bioactivities, including potential anticancer properties. The study examines the reactions carried out under ball milling conditions, emphasizing their efficiency in terms of shorter reaction times and reduced environmental impact compared to conventional methods. The ball milling reaction of evodiamine and rutaecarpine analogues resulted in yields of 63-78% and 22-61%, respectively. In addition, these compounds were tested for their cytotoxic activity, and evodiamine exhibited an IC50 of 0.75 ± 0.04 µg mL-1 against the Ca9-22 cell line. At its core, this research represents a new means to synthesise these compounds, providing a more environmentally friendly and sustainable alternative to traditional approaches.


Assuntos
Alcaloides Indólicos , Quinazolinonas , Quinazolinas/química
7.
J Alzheimers Dis Rep ; 8(1): 387-397, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549635

RESUMO

Background: The development and popularization of the Internet provides an important opportunity to advance national strategies for healthy aging, particularly the impact of the Internet on cognitive function in middle-aged and older adults. Objective: This study aimed to quantify the impact of Internet use on the cognitive health of middle-aged and older adults (aged≥45 years). Methods: We used data from the Chinese Family Panel Study (CFPS) survey, tested the robustness of the baseline findings by variable substitution and instrumental variables methods, and analyzed heterogeneity. Subsequently, five purposes of Internet use that affect cognitive function were analyzed in depth. Results: Internet use may improve cognitive function in middle-aged and older adults. The effect of Internet use on cognitive function was more pronounced in the lower age group (45-59 years), among males, in rural areas, and among middle-aged and older adults with higher levels of education. Cognitive functioning of middle-aged and older adults varied according to how often they used the Internet for entertainment, socialization, study, work, and business activities. Conclusions: The use of the Internet may be considered a practical non-pharmacological intervention to slow cognitive decline in middle-aged and older adults.

8.
Environ Toxicol ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491812

RESUMO

Protein phosphatase 2A (PP2A), a heterotrimeric holoenzyme (scaffolding, catalytic, and regulatory subunits), regulates dephosphorylation for more than half of serine/threonine phosphosites and exhibits diverse cellular functions. Although several studies on natural products and miRNAs have emphasized their impacts on PP2A regulation, their connections lack systemic organization. Moreover, only part of the PP2A family has been investigated. This review focuses on the PP2A-modulating effects of natural products and miRNAs' interactions with potential PP2A targets in cancer and non-cancer cells. PP2A-modulating natural products and miRNAs were retrieved through a literature search. Utilizing the miRDB database, potential PP2A targets of these PP2A-modulating miRNAs for the whole set (17 members) of the PP2A family were retrieved. Finally, PP2A-modulating natural products and miRNAs were linked via a literature search. This review provides systemic directions for assessing natural products and miRNAs relating to the PP2A-modulating functions in cancer and disease treatments.

9.
Brain Behav Immun ; 119: 129-145, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38552923

RESUMO

GSDMD-mediated pyroptosis occurs in the nigrostriatal pathway in Parkinson's disease animals, yet the role of GSDMD in neuroinflammation and death of dopaminergic neurons in Parkinson's disease remains elusive. Here, our in vivo and in vitro studies demonstrated that GSDMD, as a pyroptosis executor, contributed to glial reaction and death of dopaminergic neurons across different Parkinson's disease models. The ablation of the Gsdmd attenuated Parkinson's disease damage by reducing dopaminergic neuronal death, microglial activation, and detrimental transformation. Disulfiram, an inhibitor blocking GSDMD pore formation, efficiently curtailed pyroptosis, thereby lessening the pathology of Parkinson's disease. Additionally, a modification in GSDMD was identified in the blood of Parkinson's disease patients in contrast to healthy subjects. Therefore, the detected alteration in GSDMD within the blood of Parkinson's disease patients and the protective impact of disulfiram could be promising for the diagnostic and therapeutic approaches against Parkinson's disease.

10.
J Am Heart Assoc ; 13(6): e033439, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38456438

RESUMO

BACKGROUND: Subclinical myocardial injury in form of hs-cTn (high-sensitivity cardiac troponin)  levels has been associated with cognitive impairment and imaging markers of cerebral small vessel disease (SVD) in population-based and cardiovascular cohorts. Whether hs-cTn is associated with domain-specific cognitive decline and SVD burden in patients with stroke remains unknown. METHODS AND RESULTS: We analyzed patients with acute stroke without premorbid dementia from the prospective multicenter DEMDAS (DZNE [German Center for Neurodegenerative Disease]-Mechanisms of Dementia after Stroke) study. Patients underwent neuropsychological testing 6 and 12 months after the index event. Test results were classified into 5 cognitive domains (language, memory, executive function, attention, and visuospatial function). SVD markers (lacunes, cerebral microbleeds, white matter hyperintensities, and enlarged perivascular spaces) were assessed on cranial magnetic resonance imaging to constitute a global SVD score. We examined the association between hs-cTnT (hs-cTn T levels) and cognitive domains as well as the global SVD score and individual SVD markers, respectively. Measurement of cognitive and SVD-marker analyses were performed in 385 and 466 patients with available hs-cTnT levels, respectively. In analyses adjusted for demographic characteristics, cardiovascular risk factors, and cognitive status at baseline, higher hs-cTnT was negatively associated with the cognitive domains "attention" up to 12 months of follow-up (beta-coefficient, -0.273 [95% CI, -0.436 to -0.109]) and "executive function" after 12 months. Higher hs-cTnT was associated with the global SVD score (adjusted odds ratio, 1.95 [95% CI, 1.27-3.00]) and the white matter hyperintensities and lacune subscores. CONCLUSIONS: In patients with stroke, hs-cTnT is associated with a higher burden of SVD markers and cognitive function in domains linked to vascular cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01334749.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Demência , Doenças Neurodegenerativas , Acidente Vascular Cerebral , Humanos , Troponina T , Estudos Prospectivos , Doenças Neurodegenerativas/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/complicações , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Imageamento por Ressonância Magnética
11.
Cell Host Microbe ; 32(4): 606-622.e8, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38479396

RESUMO

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Animais , Humanos , Febre de Chikungunya/complicações , Proteômica , Vírus Chikungunya/genética , Citocinas/metabolismo
12.
Biomedicines ; 12(2)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38398060

RESUMO

This in vitro study examines the anti-oral cancer effects and mechanisms of a combined X-ray/SK2 treatment, i.e., X-ray and 6-n-butoxy-10-nitro-12,13-dioxa-11-azatricyclo[7.3.1.02,7]trideca-2,4,6,10-tetraene (SK2). ATP cell viability and flow cytometry-based cell cycle, apoptosis, oxidative stress, and DNA damage assessments were conducted. The X-ray/SK2 treatment exhibited lower viability in oral cancer (Ca9-22 and CAL 27) cells than in normal (Smulow-Glickman, S-G) cells, i.e., 32.0%, 46.1% vs. 59.0%, which showed more antiproliferative changes than with X-ray or SK2 treatment. Oral cancer cells under X-ray/SK2 treatment showed slight subG1 and G2/M increments and induced high annexin V-monitored apoptosis compared to X-ray or SK2 treatment. The X-ray/SK2 treatment showed higher caspase 3 and 8 levels for oral cancer cells than other treatments. X-ray/SK2 showed a higher caspase 9 level in CAL 27 cells than other treatments, while Ca9-22 cells showed similar levels under X-ray and/or SK2. The X-ray/SK2 treatment showed higher reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) depletion than other treatments. Meanwhile, the mitochondrial superoxide (MitoSOX) and glutathione levels in X-ray/SK2 treatment did not exhibit the highest rank compared to others. Moreover, oral cancer cells had higher γH2AX and/or 8-hydroxy-2-deoxyguanosine levels from X-ray/SK2 treatment than others. All these measurements for X-ray/SK2 in oral cancer cells were higher than in normal cells and attenuated by N-acetylcysteine. In conclusion, X-ray/SK2 treatment showed ROS-dependent enhanced antiproliferative, apoptotic, and DNA damage effects in oral cancer cells with a lower cytotoxic influence on normal cells.

13.
Brain Behav Immun ; 117: 399-411, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38309639

RESUMO

BACKGROUND: Autoantibodies against the potassium voltage-gated channel subfamily A member 2 (KCNA2) have been described in a few cases of neuropsychiatric disorders, but their diagnostic and pathophysiological role is currently unknown, imposing challenges to medical practice. DESIGN / METHODS: We retrospectively collected comprehensive clinical and paraclinical data of 35 patients with KCNA2 IgG autoantibodies detected in cell-based and tissue-based assays. Patients' sera and cerebrospinal fluid (CSF) were used for characterization of the antigen, clinical-serological correlations, and determination of IgG subclasses. RESULTS: KCNA2 autoantibody-positive patients (n = 35, median age at disease onset of 65 years, range of 16-83 years, 74 % male) mostly presented with cognitive impairment and/or epileptic seizures but also ataxia, gait disorder and personality changes. Serum autoantibodies belonged to IgG3 and IgG1 subclasses and titers ranged from 1:32 to 1:10,000. KCNA2 IgG was found in the CSF of 8/21 (38 %) patients and in the serum of 4/96 (4.2 %) healthy blood donors. KCNA2 autoantibodies bound to characteristic anatomical areas in the cerebellum and hippocampus of mammalian brain and juxtaparanodal regions of peripheral nerves but reacted exclusively with intracellular epitopes. A subset of four KCNA2 autoantibody-positive patients responded markedly to immunotherapy alongside with conversion to seronegativity, in particular those presenting an autoimmune encephalitis phenotype and receiving early immunotherapy. An available brain biopsy showed strong immune cell invasion. KCNA2 autoantibodies occurred in less than 10 % in association with an underlying tumor. CONCLUSION: Our data suggest that KCNA2 autoimmunity is clinically heterogeneous. Future studies should determine whether KCNA2 autoantibodies are directly pathogenic or develop secondarily. Early immunotherapy should be considered, in particular if autoantibodies occur in CSF or if clinical or diagnostic findings suggest ongoing inflammation. Suspicious clinical phenotypes include autoimmune encephalitis, atypical dementia, new-onset epilepsy and unexplained epileptic seizures.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Autoimunidade , Encefalite , Doença de Hashimoto , Animais , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Autoanticorpos , Convulsões , Mamíferos , Canal de Potássio Kv1.2
14.
Small ; : e2311393, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287737

RESUMO

Electrolyte plays a crucial role in ensuring stable operation of lithium metal batteries (LMBs). Localized high-concentration electrolytes (LHCEs) have the potential to form a robust solid-electrolyte interphase (SEI) and mitigate Li dendrite growth, making them a highly promising electrolyte option. However, the principles governing the selection of diluents, a crucial component in LHCE, have not been clearly determined, hampering the advancement of such a type of electrolyte systems. Herein, the diluents from the perspective of molecular polarity are rationally designed and developed. A moderately fluorinated solvent, 1-(1,1,2,2-tetrafluoroethoxy)propane (TNE), is employed as a diluent to create a novel LHCE. The unique molecular structure of TNE enhances the intrinsic dipole moment, thereby altering solvent interactions and the coordination environment of Li-ions in LHCE. The achieved solvation structure not only enhances the bulk properties of LHCE, but also facilitates the formation of more stable anion-derived SEIs featured with a higher proportion of inorganic species. Consequently, the corresponding full cells of both Li||LiFePO4 and Li||LiNi0.8 Co0.1 Mn0.1 O2 cells utilizing Li thin-film anodes exhibit extended long-term stability with significantly improved average Coulombic efficiency. This work offers new insights into the functions of diluents in LHCEs and provides direction for further optimizing the LHCEs for LMBs.

15.
Plant Commun ; 5(1): 100644, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-37393430

RESUMO

The molecular mechanism underlying phototherapy and light treatment, which utilize various wavelength spectra of light, including near-infrared (NIR), to cure human and plant diseases, is obscure. Here we revealed that NIR light confers antiviral immunity by positively regulating PHYTOCHROME-INTERACTING FACTOR 4 (PIF4)-activated RNA interference (RNAi) in plants. PIF4, a central transcription factor involved in light signaling, accumulates to high levels under NIR light in plants. PIF4 directly induces the transcription of two essential components of RNAi, RNA-DEPENDENT RNA POLYMERASE 6 (RDR6) and ARGONAUTE 1 (AGO1), which play important roles in resistance to both DNA and RNA viruses. Moreover, the pathogenic determinant ßC1 protein, which is evolutionarily conserved and encoded by betasatellites, interacts with PIF4 and inhibits its positive regulation of RNAi by disrupting PIF4 dimerization. These findings shed light on the molecular mechanism of PIF4-mediated plant defense and provide a new perspective for the exploration of NIR antiviral treatment.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fitocromo , Humanos , Fitocromo/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Interferência de RNA , Regulação da Expressão Gênica de Plantas
16.
Environ Toxicol ; 39(3): 1221-1234, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37921086

RESUMO

Antioral cancer drugs need a greater antiproliferative impact on cancer than on normal cells. Demethoxymurrapanine (DEMU) inhibits proliferation in several cancer cells, but an in-depth investigation was necessary. This study evaluated the proliferation-modulating effects of DEMU, focusing on oral cancer and normal cells. DEMU (0, 2, 3, and 4 µg/mL) at 48 h treatments inhibited the proliferation of oral cancer cells (the cell viability (%) for Ca9-22 cells was 100.0 ± 2.2, 75.4 ± 5.6, 26.0 ± 3.8, and 15.4 ± 1.4, and for CAL 27 cells was 100.0 ± 9.4, 77.2 ± 5.9, 57.4 ± 10.7, and 27.1 ± 1.1) more strongly than that of normal cells (the cell viability (%) for S-G cells was 100.0 ± 6.6, 91.0 ± 4.6, 95.0 ± 2.6, and 95.8 ± 5.5), although this was blocked by the antioxidant N-acetylcysteine. The presence of oxidative stress was evidenced by the increase of reactive oxygen species and mitochondrial superoxide and the downregulation of the cellular antioxidant glutathione in oral cancer cells, but these changes were minor in normal cells. DEMU also caused greater induction of the subG1 phase, extrinsic and intrinsic apoptosis (annexin V and caspases 3, 8, and 9), and DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer than in normal cells. N-acetylcysteine attenuated all these DEMU-induced changes. Together, these data demonstrate the preferential antiproliferative function of DEMU in oral cancer cells, with the preferential induction of oxidative stress, apoptosis, and DNA damage in these cancer cells, and low cytotoxicity toward normal cells.


Assuntos
Alcaloides , Neoplasias Bucais , Humanos , Antioxidantes/farmacologia , Acetilcisteína/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio , Neoplasias Bucais/tratamento farmacológico , Apoptose , Proliferação de Células , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Indóis/farmacologia , Linhagem Celular Tumoral , Dano ao DNA
17.
Orthopedics ; 47(1): 10-14, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37341567

RESUMO

Povidone-iodine is a common antiseptic demonstrating success in reducing infection rates in primary arthroplasty; however, recent data suggest that its use in revision arthroplasty may increase infection rates. This study evaluated the effect of povidone-iodine solution on antibiotic cement and investigated the connection between povidone-iodine and increased infection rates in revision arthroplasty. Sixty antibiotic cement samples (ACSs) were formed using gentamicin-impregnated cement. The ACSs were divided into three groups: group A (n=20) was subject to a 3-minute povidone-iodine soak followed by a saline rinse; group B (n=20) underwent a 3-minute saline soak; and group C (n=20) underwent only a saline rinse. The antimicrobial activity of the samples was tested using a Kirby-Bauer-like assay using Staphylococcus epidermidis. The zone of inhibition (ZOI) was measured every 24 hours for 7 days. All groups possessed the greatest antimicrobial activity at 24 hours. Group C displayed a mass-corrected ZOI of 395.2 mm/g, which was statistically greater than the group B ZOI (313.2 mm/g, P<.05) but not the group A ZOI (346.5 mm/g, P>.05). All groups demonstrated a decrease in antimicrobial activity at 48 through 96 hours, with no significant difference at any time point. Prolonged soaking of antibiotic cement in a povidone-iodine or saline solution results in elution of the antibiotic into the irrigation solution, blunting initial antibiotic concentration. When using antibiotic cement, antiseptic soaks or irrigation should be focused prior to cementation. [Orthopedics. 2024;47(1):10-14.].


Assuntos
Anti-Infecciosos Locais , Povidona-Iodo , Humanos , Povidona-Iodo/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos Locais/farmacologia , Cimentos Ósseos/farmacologia , Irrigação Terapêutica/métodos
18.
Medicine (Baltimore) ; 102(50): e36078, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38115371

RESUMO

INTRODUCTION: The role of self-expanding metal stent (SEMS) implantation as a bridge to surgery in malignant left-sided colorectal obstruction (MLCO) remains controversial. OBJECTIVE: To evaluate the safety of SEMS implantation versus emergency surgery (ER) in the treatment of MLCO. METHODS: Four major literature databases (Cochrane Library, Embase, PubMed, and Web of Science) were searched to collect articles published before April 20, 2023. After determining random or fixed-effect models based on heterogeneity tests, odds ratios (RR) or standardized mean differences (SMD) with their respective 95% confidence intervals (CI) were calculated. RESULTS: Nineteen randomized controlled studies were included. The main outcomes included overall tumor recurrence rate, 30-day mortality rate, and overall incidence of complications. Secondary outcomes included mortality-related indicators, tumor recurrence-related indicators, surgery-related indicators, and other relevant indicators. The study found that there was no significant difference in the 30-day mortality rate between the SEMS group and the er group. However, the SEMS group had a lower overall incidence of complications (RR = 0.787, P = .004), lower incision infection rate (RR = 0.472, P = .003), shorter operation time (SMD = -0.591, P = .000), lower intraoperative blood loss (SMD = -1.046, P = .000), lower intraoperative transfusion rate (RR = 0.624, P = .021), lower permanent stoma rate (RR = 0.499, P = .000), lower overall stoma rate (RR = 0.520,P = .000), shorter hospital stay (SMD = -0.643, P = .014), and more lymph node dissections during surgery (SMD = 0.222, 95% CI: 0.021-0.423, P = .031), as well as a higher primary anastomosis rate (RR = 0.472, 95% CI: 0.286-0.7 77, P = .003), among other advantages. However, the SEMS group had a higher overall tumor recurrence rate (RR = 1.339, P = .048). CONCLUSION: SEMS has significant advantages over er in relieving clinical symptoms and facilitating postoperative recovery in MLCO, but does not reduce the tumor recurrence rate. Neoadjuvant chemotherapy combined with SEMS may provide a new approach to the treatment of MLCO.


Assuntos
Neoplasias Colorretais , Obstrução Intestinal , Humanos , Obstrução Intestinal/cirurgia , Obstrução Intestinal/complicações , Recidiva Local de Neoplasia/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Stents/efeitos adversos , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Resultado do Tratamento
19.
Sci Rep ; 13(1): 20265, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37985810

RESUMO

Antrodia cinnamomea (AC) is a treasured Asian medicinal mushroom, which has attracted attention due to recent research on its effectiveness in targeting a variety of serious ailments such as cancer and liver diseases. Among different A. cinnamomea constituents, triterpenoids are regarded as the most therapeutically attractive components because of their anti-inflammatory and cytotoxic activities. In the present study, we proposed a mathematical and statistical extraction protocol to evaluate the concentrations of total ergostane and lanostane triterpenoid derivatives from the ethanolic extract of the wild fruiting bodies of A. cinnamomea (EEAC) by utilizing response surface methodology (RSM) and quantitative NMR (qNMR) approaches. The optimum response surface model showed that the variations of the investigated response variables reached more than 90%, suggesting that the developed model is accurate in explaining response variability. Furthermore, the EEAC major characteristic triterpenoids were quantified through the comparison of the HPLC-tandem MS results with those of the qNMR results. The precision of the used techniques was also evaluated. The experimental design of the EEAC optimum extraction procedure obtained by using RSM and qNMR enabled accurate characterization and quantitation of A. cinnamomea triterpenoids.


Assuntos
Agaricales , Polyporales , Triterpenos , Triterpenos/química , Carpóforos/química , Agaricales/química
20.
BMC Genomics ; 24(1): 626, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37864214

RESUMO

BACKGROUND: Phytophthora root rot caused by the oomycete Phytophthora capsici is the most devastating disease in pepper production worldwide, and current management strategies have not been effective in preventing this disease. Therefore, the use of resistant varieties was regarded as an important part of disease management of P. capsici. However, our knowledge of the molecular mechanisms underlying the defense response of pepper roots to P. capsici infection is limited. METHODS: A comprehensive transcriptome and metabolome approaches were used to dissect the molecular response of pepper to P. capsici infection in the resistant genotype A204 and the susceptible genotype A198 at 0, 24 and 48 hours post-inoculation (hpi). RESULTS: More genes and metabolites were induced at 24 hpi in A204 than A198, suggesting the prompt activation of defense responses in the resistant genotype, which can attribute two proteases, subtilisin-like protease and xylem cysteine proteinase 1, involved in pathogen recognition and signal transduction in A204. Further analysis indicated that the resistant genotype responded to P. capsici with fine regulation by the Ca2+- and salicylic acid-mediated signaling pathways, and then activation of downstream defense responses, including cell wall reinforcement and defense-related genes expression and metabolites accumulation. Among them, differentially expressed genes and differentially accumulated metabolites involved in the flavonoid biosynthesis pathways were uniquely activated in the resistant genotype A204 at 24 hpi, indicating a significant role of the flavonoid biosynthesis pathways in pepper resistance to P. capsici. CONCLUSION: The candidate transcripts may provide genetic resources that may be useful in the improvement of Phytophthora root rot-resistant characters of pepper. In addition, the model proposed in this study provides new insight into the defense response against P. capsici in pepper, and enhance our current understanding of the interaction of pepper-P. capsici.


Assuntos
Capsicum , Phytophthora , Piper nigrum , Transcriptoma , Phytophthora/fisiologia , Piper nigrum/genética , Metaboloma , Flavonoides , Doenças das Plantas/genética
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