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1.
Plant Physiol ; 195(2): 1642-1659, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38431524

RESUMO

Maize (Zea mays) smut is a common biotrophic fungal disease caused by Ustilago maydis and leads to low maize yield. Maize resistance to U. maydis is a quantitative trait. However, the molecular mechanism underlying the resistance of maize to U. maydis is poorly understood. Here, we reported that a maize mutant caused by a single gene mutation exhibited defects in both fungal resistance and plant development. maize mutant highly susceptible to U. maydis (mmsu) with a dwarf phenotype forms tumors in the ear. A map-based cloning and allelism test demonstrated that 1 gene encoding a putative arogenate dehydratase/prephenate dehydratase (ADT/PDT) is responsible for the phenotypes of the mmsu and was designated as ZmADT2. Combined transcriptomic and metabolomic analyses revealed that mmsu had substantial differences in multiple metabolic pathways in response to U. maydis infection compared with the wild type. Disruption of ZmADT2 caused damage to the chloroplast ultrastructure and function, metabolic flux redirection, and reduced the amounts of salicylic acid (SA) and lignin, leading to susceptibility to U. maydis and dwarf phenotype. These results suggested that ZmADT2 is required for maintaining metabolic flux, as well as resistance to U. maydis and plant development in maize. Meanwhile, our findings provided insights into the maize response mechanism to U. maydis infection.


Assuntos
Resistência à Doença , Doenças das Plantas , Zea mays , Zea mays/microbiologia , Zea mays/genética , Zea mays/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Resistência à Doença/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Hidroliases/genética , Hidroliases/metabolismo , Basidiomycota/fisiologia , Regulação da Expressão Gênica de Plantas , Fenótipo , Mutação/genética , Ácido Salicílico/metabolismo , Ustilago/genética
2.
EMBO Rep ; 24(4): e55681, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-36744362

RESUMO

N6 -Methyladenosine (m6 A) is the most abundant epitranscriptomic mark and plays a fundamental role in almost every aspect of mRNA metabolism. Although m6 A writers and readers have been widely studied, the roles of m6 A erasers are not well-understood. Here, we investigate the role of FTO, one of the m6 A erasers, in natural killer (NK) cell immunity. We observe that FTO-deficient NK cells are hyperactivated. Fto knockout (Fto-/- ) mouse NK cells prevent melanoma metastasis in vivo, and FTO-deficient human NK cells enhance the antitumor response against leukemia in vitro. We find that FTO negatively regulates IL-2/15-driven JAK/STAT signaling by increasing the mRNA stability of suppressor of cytokine signaling protein (SOCS) family genes. Our results suggest that FTO is an essential modulator of NK cell immunity, providing a new immunotherapeutic strategy for allogeneic NK cell therapies.


Assuntos
Antineoplásicos , Células Matadoras Naturais , Animais , Camundongos , Humanos , Transdução de Sinais , Citocinas , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética
3.
PLoS Genet ; 18(6): e1010280, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35737710

RESUMO

Aedes albopictus is one of the most invasive insect species in the world and an effective vector for many important arboviruses. We reported previously that Ae. albopictus Nix (AalNix) is the male-determining factor of this species. However, whether AalNix alone is sufficient to initiate male development is unknown. Transgenic lines that express each of the three AalNix isoforms from the native promoter were obtained using piggyBac transformation. We verified the stable expression of AalNix isoforms in the transgenic lines and confirm that one isoform, AalNix3&4, is sufficient to convert females into fertile males (pseudo-males) that are indistinguishable from wild-type males. We also established a stable sex-converted female mosquito strain, AalNix3&4-♂4-pseudo-male. The pseudo-male mosquitoes can fly and mate normally with wild-type female, although their mating competitiveness is lower than wild-type. This work further clarifies the role of AalNix in the sex determination pathway and will facilitate the development of Ae. albopictus control strategies that rely on male-only releases such as SIT and sex-ratio distortion.


Assuntos
Aedes , Aedes/genética , Aedes/metabolismo , Animais , Animais Geneticamente Modificados , Feminino , Espécies Introduzidas , Masculino , Mosquitos Vetores/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Reprodução
4.
Lancet Oncol ; 25(7): 843-852, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38852601

RESUMO

BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA , Instabilidade de Microssatélites , Terapia Neoadjuvante , Piridinas , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Terapia Neoadjuvante/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Idoso , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto Jovem , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Adolescente
5.
J Cell Mol Med ; 28(12): e18481, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899542

RESUMO

Bacillus subtilis relies on biofilms for survival in harsh environments. Extracellular polymeric substance (EPS) is a crucial component of biofilms, yet the dynamics of EPS production in single cells remain elusive. To unveil the modulation of EPS synthesis, we built a minimal network model comprising the SinI-SinR-SlrR module, Spo0A, and EPS. Stochastic simulations revealed that antagonistic interplay between SinI and SinR enables EPS production in bursts. SlrR widens these bursts and increases their frequency by stabilizing SinR-SlrR complexes and depleting free SinR. DNA replication and chromosomal positioning of key genes dictate pulsatile changes in the slrR:sinR gene dosage ratio (gr) and Spo0A-P levels, each promoting EPS production in distinct phases of the cell cycle. As the cell cycle lengthens with nutrient stress, the duty cycle of gr pulsing decreases, whereas the amplitude of Spo0A-P pulses elevates. This coordinated response facilitates keeping a constant proportion of EPS-secreting cells within colonies across diverse nutrient conditions. Our results suggest that bacteria may 'encode' eps expression through strategic chromosomal organization. This work illuminates how stochastic protein interactions, gene copy number imbalance, and cell-cycle dynamics orchestrate EPS synthesis, offering a deeper understanding of biofilm formation.


Assuntos
Bacillus subtilis , Proteínas de Bactérias , Biofilmes , Replicação do DNA , Regulação Bacteriana da Expressão Gênica , Biofilmes/crescimento & desenvolvimento , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Bacillus subtilis/fisiologia , Replicação do DNA/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Ciclo Celular/genética
6.
Clin Immunol ; 263: 110232, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701960

RESUMO

IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one form of glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. The level of plasma level of C5a (p < 0.001), soluble C5b-9 (p = 0.018), FHR5 (p < 0.001) were all significantly higher in Group CoV (33 patients with renal biopsy-proven IgAN experienced COVID-19) compared with Group non-CoV (44 patients with IgAN without COVID-19), respectively. Compared with Group non-CoV, the intensity of glomerular C4d (p = 0.017) and MAC deposition (p < 0.001) and Gd-IgA1 deposition (p = 0.005) were much stronger in Group CoV. Our finding revealed that for IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, and increased glomerular deposition of Gd-IgA1, which may lead to renal dysfunction and promote renal progression in IgAN patients.


Assuntos
COVID-19 , Glomerulonefrite por IGA , SARS-CoV-2 , Humanos , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/sangue , COVID-19/imunologia , COVID-19/complicações , Feminino , Masculino , Adulto , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Ativação do Complemento/imunologia , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Glomérulos Renais/patologia , Glomérulos Renais/imunologia , Complemento C5a/imunologia , Complemento C5a/metabolismo
7.
Small ; : e2402981, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838089

RESUMO

To address the imperative challenge of producing hydrogen in a low-energy consumption electrocatalytic system, this study emphasizes the utilization of thermodynamically favorable biomass oxidation for achieving energy-efficient hydrogen generation. This research integrates ultralow PtO2-loaded flower-like nanosheets (denoted as PtO2@Cu2O/Cu FNs) with Cu0/Cu+ pairs and Pt─O bonds, thereby yielding substantial enhancement in both hydrogen evolution reaction (HER, -0.042 VRHE at 10 mA cm-2) and furfural oxidation reaction (FFOR, 0.09 VRHE at 10 mA cm-2). As validated by DFT calculations, the dual built-in electric field (BIEF) is elucidated as the driving force behind the enhanced activities, in which Pt─O bonds expedite the HER, while Cu+/Cu0 promotes low-potential FFOR. By coupling the FFOR and HER together, the resulting bipolar-hydrogen production system requires a low power input (0.5072 kWh per m3) for producing H2. The system can generate bipolar hydrogen and high value-added furoic acid, significantly enhancing hydrogen production efficiency and concurrently mitigating energy consumption.

8.
Small ; 20(5): e2304452, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37752683

RESUMO

Carbon-based hole transport layer-free perovskite solar cells (PSCs) based on methylammonium lead triiodide (MAPbI3 ) have become one of the research focus due to low cost, easy preparation, and good optoelectronic properties. However, instability of perovskite under vacancy defects and stress-strain makes it difficult to achieve high-efficiency and stable power output. Here, a soft-structured long-chain 2D pentanamine iodide (abbreviated as "PI") is used to improve perovskite quality and interfacial mechanical compatibility. PI containing CH3 (CH2 )4 NH3 + and I- ions not only passivate defects at grain boundaries, but also effectively alleviate residual stress during high temperature annealing via decreasing Young's modulus of perovskite film. Most importantly, PI effectively increases matching degree of Young's modulus between MAPbI3 (47.1 GPa) and carbon (6.7 GPa), and strengthens adhesive fracture energy (Gc ) between perovskite and carbon, which is helpful for outward release of nascent interfacial stress generated under service conditions. Consequently, photoelectric conversion efficiency (PCE) of optimal device is enhanced from 10.85% to 13.76% and operational stability is also significantly improved. 83.1% output is maintained after aging for 720 h at room temperature and 25-60% relative humidity (RH). This strategy of regulation from chemistry and physics provides a strategy for efficient and stable carbon-based PSCs.

9.
J Magn Reson Imaging ; 59(5): 1820-1831, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37830268

RESUMO

BACKGROUND: The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear. HYPOTHESIS: MR uniformity ratio estimates (URE) can detect LVMD and assess STEMI prognosis. STUDY TYPE: Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453). POPULATION: Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls. FIELD STRENGTH/SEQUENCE: 3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging. ASSESSMENT: MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared. STATISTICAL TESTS: The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant. RESULTS: CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF. DATA CONCLUSION: CURE and RURE may be useful to evaluate long-term prognosis after STEMI. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Feminino , Humanos , Masculino , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Volume Sistólico , Função Ventricular Esquerda , Estudos Prospectivos , Meios de Contraste , Estudos Retrospectivos , Gadolínio , Imageamento por Ressonância Magnética/métodos , Prognóstico , Intervenção Coronária Percutânea/efeitos adversos , Imagem Cinética por Ressonância Magnética/métodos
10.
J Natl Compr Canc Netw ; 22(3)2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498975

RESUMO

BACKGROUND: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy. METHODS: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. CONCLUSIONS: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.


Assuntos
Neoplasias Colorretais , Neoplasias Retais , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA , Imunoterapia , Instabilidade de Microssatélites , Terapia Neoadjuvante , Neoplasias Retais/genética , Neoplasias Retais/terapia , Estudos Retrospectivos , Resultado do Tratamento
11.
Prostaglandins Other Lipid Mediat ; 170: 106803, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38040190

RESUMO

Resolvin (Rv) and lipoxin (Lx) play important regulative roles in the development of several inflammation-related diseases. The dysregulation of their metabolic network is believed to be closely related to the occurrence and development of asthma. The Hyssopus Cuspidatus Boriss extract (SXCF) has long been used as a treatment for asthma, while the mechanism of anti-inflammatory and anti-asthma action targeting Rv and Lx has not been thoroughly investigated. In this study, we aimed to investigate the effects of SXCF on Rv, Lx in ovalbumin (OVA)-sensitized asthmatic mice. The changes of Rv, Lx before and after drug administration were analyzed based on high sensitivity chromatography-multiple response monitoring (UHPLC-MRM) analysis and multivariate statistics. The pathology exploration included behavioral changes of mice, IgE in serum, cytokines in BALF, and lung tissue sections stained with H&E. It was found that SXCF significantly modulated the metabolic disturbance of Rv, Lx due to asthma. Its modulation effect was significantly better than that of dexamethasone and rosmarinic acid which is the first-line clinical medicine and the main component of Hyssopus Cuspidatus Boriss, respectively. SXCF is demonstrated to be a potential anti-asthmatic drug with significant disease-modifying effects on OVA-induced asthma. The modulation of Rv and Lx is a possible underlying mechanism of the SXCF effects.


Assuntos
Antiasmáticos , Asma , Lipoxinas , Camundongos , Animais , Lipoxinas/farmacologia , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma/metabolismo , Antiasmáticos/efeitos adversos , Pulmão/metabolismo , Citocinas/metabolismo , Extratos Vegetais/farmacologia , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças
12.
Mol Biol Rep ; 51(1): 518, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622261

RESUMO

BACKGROUND: Cold atmospheric plasma (CAP) has been widely used in biomedical research, especially in vitro cancer therapy. Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor originating from epidermal keratinocytes. However, the mechanism of CAP therapy on CSCC remains unclear. METHODS AND RESULTS: The animal models of CSCC induced by 7,12-dimethylbenz(a) anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) were constructed. For the CAP treatment group, after each TPA application, CAP was administered for 3 min twice weekly after drying. HE staining were used to detect the pathological status of tumor tissue in each group. The levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 were evaluated by western blot and qPCR. TUNEL staining were used to detect apoptosis in tumor tissues. In vivo, serum samples were used for ELISA of total ROS. MTT assay was used to detect the viability of A431 cells. Western blot and qPCR were used to detect the levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 in A431 cells. A431 cell proliferation was examined by colony formation assay. The proportions of apoptosis of A431 cells were detected by flow cytometry. Transwell assessed the ability of A431 cells migration and proliferation. We found that CAP could induce skin cancer cells apoptosis and inhibit the progress of skin cancer. Through experiments in vitro, reactive oxygen species (ROS) generated by N-acetylcysteine (NAC) and CAP inhibited the proliferation and migration of A431 skin cancer cells while promoting apoptosis. CONCLUSIONS: These evidences suggest the protective effect of CAP in CSCC, and CAP has the potential clinical application of CSCC.


Assuntos
Carcinoma de Células Escamosas , Gases em Plasma , Neoplasias Cutâneas , Animais , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Espécies Reativas de Oxigênio/farmacologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Gases em Plasma/farmacologia , Antígeno Nuclear de Célula em Proliferação/genética , Proteína X Associada a bcl-2 , Apoptose , Linhagem Celular Tumoral , Proliferação de Células
13.
Anal Bioanal Chem ; 416(2): 467-474, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37993551

RESUMO

Natural bioactive compounds (NBCs) are widely used in clinical treatment. For example, Tripterygium wilfordii Hook f. is commonly known in China as Lei-Gong-Teng which means thunder god vine. This herb is widely distributed in Eastern and Southern China, Korea, and Japan. The natural bioactive compounds of this herb can be extracted and made into tripterygium glycoside tablets. It is one of the most commonly used and effective traditional Chinese herbal medicines against rheumatoid arthritis (RA), nephrotic syndrome (NS), autoimmune hepatis (AIH), and so on. However, many NBCs are difficult to reliably quantify in the serum due to the effects of matrix and RSD. In addition, the targeted compound's internal standard (IS) is rarely sold due to the complex isotope internal standard synthesis pathway. In this study, a new quantitation method for 18O labeling combined with off-line SPE was formulated. We contrasted the recoveries and matrix effects of various separation methods in order to choose the best method. Furthermore, we optimized the conditions for SPE loading and washing. An isotopic internal standard was prepared by the 16O/18O exchanging reaction in order to eliminate the matrix effects. The method's accuracy and precision met the requirements for method validation. The recovery of this method was close to 60%. The relative standard deviation (RSD) of the high-concentration sample was 2%, and the limit of detection (LOD) was 1 ng/mL. This method could be used to analyze the clinical serum concentration of demethylzeylasteral. Sixty samples were collected from 10 patients with diabetes nephropathy. The quantitation results of demethylzeylasteral in patients' serum obtained using this method exhibited a correlation between therapeutic drug monitoring (TDM) and decreased urinary protein. This work may have broad implications for the study of drug metabolism in vivo and the clinical application of low-abundance and difficult-to-quantify NBCs.


Assuntos
Artrite Reumatoide , Medicamentos de Ervas Chinesas , Triterpenos , Humanos , Artrite Reumatoide/tratamento farmacológico , Glicosídeos
14.
J Nat Prod ; 87(1): 38-49, 2024 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-38207331

RESUMO

Physalis angulata var. villosa is a plant possessing abundant withanolides, but in-depth research is lacking. In our ongoing study of P. angulata var. villosa, 15 previously undescribed withanolides (1-15), along with 21 known analogs (16-36), were isolated from the whole plant. The structures of the withanolides (1-15) were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and ECD data. Additionally, the application of γ-gauche effects with the help of ROESY correlations led to the formulation of empirical rules for withanolides with 14-OH/15-OAc to rapidly determine the 14-OH orientations, making it possible to propose configurational revisions of 19 previously reported analogs (1'-19'). Withanolides 1, 4-6, and 10 showed potent cytotoxic activities against three human cancer cell lines (HCT-116, MDA-MB-231, and A549).


Assuntos
Antineoplásicos Fitogênicos , Physalis , Vitanolídeos , Humanos , Vitanolídeos/farmacologia , Vitanolídeos/química , Physalis/química , Extratos Vegetais/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Linhagem Celular , Estrutura Molecular
15.
Bioorg Chem ; 150: 107594, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38941701

RESUMO

Inhibition of human dihydroorotate dehydrogenase (hDHODH) represents a promising strategy for suppressing the proliferation of cancer cells. To identify novel and potent hDHODH inhibitors, a total of 28 piperine derivatives were designed and synthesized. Their cytotoxicities against three human cancer cell lines (NCI-H226, HCT-116, and MDA-MB-231) and hDHODH inhibitory activities were also evaluated. Among them, compound H19, exhibited the strongest inhibitory activities (NCI-H226 IC50 = 0.95 µM, hDHODH IC50 = 0.21 µM). Further pharmacological investigations revealed that H19 exerted anticancer effects by inducing ferroptosis in NCI-H226 cells, with its cytotoxicity being reversed by ferroptosis inhibitors. This was supported by the intracellular growth or decline of ferroptosis markers, including lipid peroxidation, Fe2+, GSH, and 4-HNE. Overall, H19 emerges as a promising hDHODH inhibitor with potential anticancer properties warranting development.

16.
BMC Geriatr ; 24(1): 189, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409011

RESUMO

BACKGROUND: There are a variety of determinants that are key to functional disability of older adults. However, little is known regarding the relationship between cognitive frailty and disability among older people. The aims of this study were to examine the associations between cognitive frailty and its six components with instrumental activities of daily living (IADL) functioning in community-dwelling older adults. METHODS: A total of 313 community-dwelling older adults (aged ≥ 65 years) were recruited from eight community centers in central China. Cognitive frailty was operationalized using the Mini-Mental State Examination for the evaluation of cognitive status and the Fried criteria for the evaluation of physical frailty. The outcome was functional disability assessed by the IADL scale. The association between cognitive frailty, as well as its components, and IADL limitations was identified by conducting binary logistic regression analysis. RESULTS: The prevalence of cognitive frailty was 8.9% in this study. The results showed that cognitive frailty (OR = 22.86) and frailty without cognitive impairment (OR = 8.15) were associated with IADL limitations. Subdimensions of cognitive frailty, exhaustion, weakness, low physical activity and cognitive impairment components were independently associated with IADL limitations. CONCLUSION: Cognitive frailty was associated with a higher prevalence of disability. Interventions for improving cognitive frailty should be developed to prevent IADL disability among community-dwelling older adults in China.


Assuntos
Fragilidade , Idoso , Humanos , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Idoso Fragilizado/psicologia , Vida Independente/psicologia , Estudos Transversais , Atividades Cotidianas , China/epidemiologia , Cognição , Avaliação Geriátrica/métodos
17.
Chaos ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38574280

RESUMO

Reconstructing complex networks and predicting the dynamics are particularly challenging in real-world applications because the available information and data are incomplete. We develop a unified collaborative deep-learning framework consisting of three modules: network inference, state estimation, and dynamical learning. The complete network structure is first inferred and the states of the unobserved nodes are estimated, based on which the dynamical learning module is activated to determine the dynamical evolution rules. An alternating parameter updating strategy is deployed to improve the inference and prediction accuracy. Our framework outperforms baseline methods for synthetic and empirical networks hosting a variety of dynamical processes. A reciprocity emerges between network inference and dynamical prediction: better inference of network structure improves the accuracy of dynamical prediction, and vice versa. We demonstrate the superior performance of our framework on an influenza dataset consisting of 37 US States and a PM2.5 dataset covering 184 cities in China.

18.
J Clin Nurs ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797930

RESUMO

AIMS: To identify the multiple mediating effects of resilience and depression between social support and self-care ability among patients with breast cancer during rehabilitation to provide reference for developing and implementing targeted interventions. DESIGN: A cross-sectional study reported according to the STROBE checklist. METHODS: A convenience sample of 320 patients with breast cancer during rehabilitation was recruited from one hospital in China. Data were collected from April to August 2022 using a self-report questionnaire, including the demographic and clinical information, Appraisal of Self-Care Agency Scale-Revised, Multidimensional Scale of Perceived Social Support, Connor-Davidson Resilience Scale-10 item, and Patient Health Questionnaire-9. The mediation analysis was conducted using the SPSS Process macro. RESULTS: Self-care ability was positively associated with social support (ß = .229) and resilience (ß = .290), and negatively associated with depression (ß = -.208). The relationship between social support and self-care ability was mediated by resilience and depression, respectively, and together in serial. The multiple mediating effects accounted for 34.0% of the total effect of social support on self-care ability. CONCLUSION: Our findings identify resilience and depression as multiple mediators between social support and self-care ability and highlight the important roles of social support, resilience and depression in improving self-care ability. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should pay great attention to the underlying mechanisms of how social support affects patients' self-care ability during breast cancer rehabilitation. Integrated intervention programmes targeted at enhancing social support, building resilience and alleviating depression might be beneficial to the improvement of self-care ability. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies was applied to report the results.

19.
J Clin Nurs ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716880

RESUMO

AIMS: To comprehensively synthesise existing evidence from systematic reviews regarding the effects of exercise interventions on physical, psychological and social outcomes in frail older adults to provide reference for clinical practice. BACKGROUND: Frailty is highly prevalent in older adults and associated with increased adverse health outcomes. Some systematic reviews have assessed the effectiveness of exercise interventions in frail older adults with varied inclusion criteria, methodology quality, types of exercise and outcome measures. DESIGN: An overview of systematic reviews reported following the PRISMA checklist. METHODS: PubMed, Embase, CINAHL, Web of Science and Cochrane database were searched from inception until June 2023 to identify relevant systematic reviews with or without meta-analysis of randomised controlled trails. Two reviewers independently selected articles, extracted data, assessed quality and summarised findings. RESULTS: A total of 17 systematic reviews were included, with methodology quality varying from moderate to critically low. The most frequent types of exercise were multicomponent exercise and resistance-based exercise in community and long-term care facilities, respectively. Exercise interventions had positive effects on most physical outcomes and depression, but inconsistent effects on cognitive function and quality of life. The quality of the evidence for most outcomes was low and very low. CONCLUSIONS: This overview highlights the importance of exercise interventions to improve physical, psychological and social aspects in frail older adults and provides evidence on characteristics of exercise interventions for frailty in various settings. RELEVANCE TO CLINICAL PRACTICE: Multicomponent exercise and resistance-based exercise should be recommended for frail older adults. There is a need of more well-designed research with large sample size and validated definition of frailty. Long-term effects, adherence during and after exercise interventions, adverse events and cost-effectiveness should be emphasised in future studies. TRIAL AND PROTOCOL REGISTRATION: The overview protocol was registered on the International Prospective Register of Systematic reviews (CRD 42021281327). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were applied to report the results.

20.
J Asian Nat Prod Res ; 26(1): 18-25, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38189299

RESUMO

Four new nortriterpenoid alkaloids, namely buxrugulines E-H (1-4), along with five known ones (5-9), were isolated from the twigs and leaves of Buxus rugulosa. Their structures were identified based on extensive NMR data and MS spectroscopic analyses. Our bioassays revealed that compounds 5, 6 and 8 exhibited potent cytotoxicity in vitro against MCF-7 cell lines, with IC50 values ranging from 6.70 to 11.00 µM, respectively.


Assuntos
Alcaloides , Buxus , Triterpenos , Humanos , Buxus/química , Triterpenos/farmacologia , Triterpenos/química , Alcaloides/farmacologia , Alcaloides/química , Células MCF-7 , Espectroscopia de Ressonância Magnética , Estrutura Molecular
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