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1.
Front Plant Sci ; 15: 1450999, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39359633

RESUMO

The development and quality of tea plants (Camellia sinensis (L.) O. Ktze.) are greatly hampered by drought stress (DS), which affects them in a number of ways, including by interfering with their metabolism of nitrogen (N). Arbuscular mycorrhizal fungi (AMF) are known to enhance water and nutrient absorption in plants, but their specific effects on tea plant N metabolism under DS and the associated regulatory mechanisms remain unclear. This study aimed to evaluate the impact of Claroideoglomus etunicatum inoculation on N assimilation in tea plants (C. sinensis cv. Fuding Dabaicha) under well-watered (WW) and DS conditions, and to explore potential molecular mechanisms. After 8 weeks of DS treatment, root mycorrhizal colonization was significantly inhibited, and the biomass of tea shoots and roots, as well as the contents of various amino acids (AAs) were reduced. However, AMF inoculation significantly increased the contents of tea polyphenols and catechins in leaves by 13.74%-36.90% under both WW and DS conditions. Additionally, mycorrhizal colonization notably increased N content by 12.65%-35.70%, various AAs by 11.88%-325.42%, and enzymatic activities associated with N metabolism by 3.80%-147.62% in both leaves and roots. Gene expression analysis revealed a universal upregulation of N assimilation-related genes (CsAMT1;2, CsAMT3;1, CsGS1, CsNADH-GOGAT, CsTS2, CsGGT1, and CsADC) in AMF-colonized tea roots, regardless of water status. Under DS condition, AMF inoculation significantly upregulated the expressions of CsNRT1;2, CsNRT1;5, CsNRT2;5, CsNR, CsGS1, CsGDH1, CsGDH2, CsTS2, CsGGT1, CsGGT3, and CsSAMDC in tea leaves. These findings suggest that AMF improved tea plant adaptability to DS by enhancing N absorption and assimilation, accompanied by the synthesis and accumulation of various AAs, such as Glu, Gln, Asp, Lys, Arg, GABA and Pro. This is achieved through the upregulation of N metabolism-related genes and the activation of related enzymes in tea plants under DS condition. These findings provide valuable insights into the role of AMF in regulating tea plant N metabolism and enhancing stress tolerance.

2.
Yi Chuan ; 46(9): 737-749, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39275873

RESUMO

Rapeseed is one important oil crop in China. However, its planting benefit is frequently affected by environmental stresses such as drought in the northwest region of China. The abscisic acid(ABA) signaling pathway plays an important role in plant abiotic stress response and tolerance, and ABFs/AREBs(ABA-responsive element binding factors/ABA-responsive element binding proteins) are the core transcription factors that regulate the expression of ABA-responsive genes. To dissect the key transcription factors mediated abiotic stress, we mainly characterized abscisic acid insensitive 5(BnaABI5) in rapeseed, including its subcellular localization, expression pattern in response to various stress and tissue-specific expression analysis, transcriptional activity analysis as well as interaction screening with BnaMPKs(mitogen-activated protein kinases). Our results showed that the BnaABI5-GFP fusion protein was localized in the nucleus, and its transcript level is induced by drought stress and was mainly expressed in the roots of rapeseed. Furthermore, BnaABI5 showed transcriptional activation activity through a yeast transactivation assay and it also activated the promoter activity of EM6 target gene in the transient expression system in tobacco leaves. Moreover, BnaABI5 interacted with BnaMPK6 and BnaMPK13 through BiFC and Y2H analysis. This study preliminarily explored the expression characteristics of transcription factor BnaABI5 and its interaction with BnaMPKs, which might help us for further understanding the function of BnaABI5.


Assuntos
Brassica napus , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Fatores de Transcrição , Brassica napus/genética , Brassica napus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico/genética , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia
3.
BMC Med ; 22(1): 407, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304842

RESUMO

BACKGROUND: Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. METHODS: This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. RESULTS: The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P < 0.05). Based on these six features, the random forest model (mtry = 5, 75%p) exhibited the best predictive performance among 97 machine learning models, with the area under the curve values reaching 0.983, 1, and 0.905 for the entire cohort, training set, and validation set, respectively. This model significantly outperformed single indicators. The DCA curve confirmed the clinical utility of this model. CONCLUSIONS: In this study, we developed a machine learning-based predictive model for DGF following pediatric kidney transplantation, termed DGF-RS, which integrates both donor and recipient characteristics. The model demonstrated excellent predictive accuracy and provides essential guidance for clinical decision-making. These findings contribute to our understanding of the pathogenesis of DGF.


Assuntos
Função Retardada do Enxerto , Transplante de Rim , Aprendizado de Máquina , Doadores de Tecidos , Humanos , Transplante de Rim/efeitos adversos , Feminino , Masculino , Criança , Estudos Retrospectivos , Adolescente , Pré-Escolar , Lactente
4.
Exp Cell Res ; 442(2): 114253, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39271099

RESUMO

OBJECTIVE: Macrophage polarization and the resulting phenotype have versatile roles in atherosclerosis. The study aims to decipher the role of SIRT1 in regulating macrophage phenotypes and atherosclerosis development. METHODS: Two mouse lines of SIRT1△Mac/ApoE-/- and SIRT1fl/fl/ApoE-/- were fed with high-fat diet to generate atherosclerotic lesion. Mouse peritoneal macrophages were isolated and transfected with SIRT1-overexpressing vector or vector-null. RESULTS: The SIRT1△Mac/ApoE-/- mice exhibited greater atherosclerotic lesions, stronger immunofluorescence staining for M1-like macrophage marker, iNOS, and weaker immunofluorescence staining for M2-like macrophage marker, Arginase-1, than the SIRT1fl/fl/ApoE-/- littermates. The gene expressions of M1 markers (IL-1ß, IL-6, and iNOS) were increased and those of M2 markers (IL-10 and Arg-1) decreased in both aortic roots and peritoneal macrophages from SIRT1△Mac/ApoE-/- mice, whereas SIRT1 overexpression rectified the changes in M1/M2 expression. A declined expression of TIMP3 with an increased expression of ADAM17 was noted in SIRT1△Mac/ApoE-/- macrophages, whereas SIRT1 overexpression rescued TIMP3 expression and inhibited ADAM17 expression. CONCLUSION: Our data suggest that SIRT1 deficiency may promote macrophage M1 polarization and regulate the TIMP3/ADAM17 pathway thus favoring atherosclerosis development, indicating an anti-atherosclerotic role of macrophage SIRT1.

5.
Ecotoxicol Environ Saf ; 285: 117133, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39342757

RESUMO

Atherosclerosis (AS) and its related cardiovascular diseases (CVDs) remain the most frequent cause of morbidity and mortality worldwide. Researches showed that bisphenol A (BPA) exposure might exacerbate AS progression. However, as an analogue of BPA, little is known about the cardiovascular toxicity of bisphenol S (BPS), especially whether BPS exposure has the pro-atherogenic effects in mammals is still unknown. Here, we firstly constructed an apolipoprotein E knockout (ApoE-/-) mouse model and cultured cells to investigate the risk of BPS on AS and explore the underlying mechanisms. Results showed that prolonged exposure to 50 µg/kg body weight (bw)/day BPS indeed aggravated AS lesions both in the en face aortas and aortic sinuses of ApoE-/- mice. Moreover, BPS were found to be implicated in the AS pathological process: 1) stimulates adhesion molecule expression to promote monocyte-endothelial cells (ECs) adhesion with 3.6 times more than the control group in vivo; 2) increases the distribution of vascular smooth muscle cells (VSMCs) with 9.3 times more than the control group in vivo, possibly through the migration of VSMCs; and 3) induces an inflammatory response by increasing the number of macrophages (MACs), with 3.7 times more than the control group in vivo, and the release of inflammatory mediators. Furthermore, we have identified eight significant AS-related genes induced by BPS, including angiopoietin-like protein 7 (Angptl17) and lipocalin-2 (Lcn2) in ECs; matrix metalloproteinase 9 (Mmp13), secreted phosphoprotein 1 (Spp1), and collagen type II alpha 1 (Col2a1) in VSMCs; and kininogen 1 (Kng1), integrin alpha X (Itgax), and MAC-expressed gene 1 (Mpeg1) in MACs. Overall, this study firstly found BPS exposure could exacerbate mammalian AS and might also provide a theoretical basis for elucidating BPS and its analogues induced AS and related CVDs.

6.
JAMA ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39283649

RESUMO

Importance: The effect of high-intensity noninvasive positive pressure ventilation (NPPV) on the need for endotracheal intubation in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) is unknown. Objective: To determine whether the use of high-intensity NPPV vs low-intensity NPPV reduces the need for endotracheal intubation in patients with an acute exacerbation of COPD and hypercapnia. Design, Setting, and Participants: Randomized clinical trial conducted at 30 general respiratory non-intensive care unit wards of Chinese hospitals from January 3, 2019, to January 31, 2022; the last 90-day follow-up was on April 22, 2022. The included patients had an acute exacerbation of COPD and a Paco2 level greater than 45 mm Hg after receiving 6 hours of low-intensity NPPV. Interventions: Patients were randomized 1:1 to receive high-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume 10 mL/kg to 15 mL/kg of predicted body weight (n = 147) or to continue receiving low-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume of 6 mL/kg to 10 mL/kg of predicted body weight (n = 153). Patients in the low-intensity NPPV group who met the prespecified criteria for the need for endotracheal intubation were allowed to crossover to high-intensity NPPV. Main Outcomes and Measures: The primary outcome was the need for endotracheal intubation during hospitalization, which was defined by prespecified criteria. There were 15 prespecified secondary outcomes, including endotracheal intubation. Results: The trial was terminated by the data and safety monitoring board and the trial steering committee after an interim analysis of the first 300 patients. Among the 300 patients who completed the trial (mean age, 73 years [SD, 10 years]; 68% were men), all were included in the analysis. The primary outcome of meeting prespecified criteria for the need for endotracheal intubation occurred in 7 of 147 patients (4.8%) in the high-intensity NPPV group vs 21 of 153 (13.7%) in the low-intensity NPPV group (absolute difference, -9.0% [95% CI, -15.4% to -2.5%], 1-sided P = .004). However, rates of endotracheal intubation did not significantly differ between groups (3.4% [5/147] in the high-intensity NPPV group vs 3.9% [6/153] in the low-intensity NPPV group; absolute difference, -0.5% [95% CI, -4.8% to 3.7%], P = .81). Abdominal distension occurred more frequently in the high-intensity NPPV group (37.4% [55/147]) compared with the low-intensity NPPV group (25.5% [39/153]). Conclusions and Relevance: Patients with COPD and persistent hypercapnia in the high-intensity NPPV group (vs patients in the low-intensity NPPV group) were significantly less likely to meet criteria for the need for endotracheal intubation; however, patients in the low-intensity NPPV group were allowed to crossover to high-intensity NPPV, and the between-group rate of endotracheal intubation was not significantly different. Trial Registration: ClinicalTrials.gov Identifier: NCT02985918.

7.
Eur J Neurol ; : e16449, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39236309

RESUMO

BACKGROUND AND PURPOSE: This study was undertaken to conduct a meta-analysis on the prevalence of aspiration pneumonia (AP) and hospital mortality in Parkinson disease (PD) as well as the risk of AP in PD patients compared to controls. METHODS: We searched MEDLINE and Embase from inception to 19 March 2024 to identify cross-sectional, cohort, and case-control studies comparing the frequency of AP and hospital mortality in PD patients. We computed risk ratios (RRs) with accompanying 95% confidence intervals (CIs) for each study and pooled the results using a random-effects meta-analysis. RESULTS: A total of 781 studies were initially screened, and 13 studies involving 541,785,587 patients were included. Patients with PD had >3 times higher risk of AP compared to controls (RR = 3.30, 95% CI = 1.82-6.00, p < 0.0001). This increased risk was similar in both cohort studies (RR = 3.01, 95% CI = 1.10-8.24, p = 0.03) and case-control studies (RR = 3.86, 95% CI = 3.84-3.87, p < 0.00001). The prevalence of AP in 12 studies was 2.74% (95% CI = 1.69-4.41), and hospital mortality was 10% in six studies (10.0%, 95% CI = 5.32-18.0). Prevalence of AP was higher in studies with smaller sample size (5.26%, 95% CI = 3.08-8.83 vs. 2.06%, 95% CI = 1.19-3.55, p = 0.02). CONCLUSIONS: Our meta-analysis showed that patients with PD had >3 times higher risk of AP, with an average 2.74% prevalence and 10.0% hospital mortality. Early recognition and treatment of AP in PD patients will help reduce morbidity and mortality. A multidisciplinary holistic approach is needed to address the multifactorial causes of AP.

8.
Zhonghua Nan Ke Xue ; 30(7): 597-603, 2024 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-39212393

RESUMO

OBJECTIVE: To explore the clinical value of prostatic exosomal protein (PSEP) and PSA in the diagnosis of PCa with PSA in the gray zone (4-10 µg/L) and Prostate Imaging Reporting and Data System category 3 (PI-RADS-3) lesions. METHODS: From 2019 to 2022, 211 patients with the PSA gray zone and PI-RADS-3 lesions underwent prostate multi-parameter MRI, prostate needle biopsy or transurethral resection/enucleation of the prostate. We collected the baseline urine samples from the patients, examined the content of PSEP in the urine by ELISA and evaluated the performance of PSEP and PSA in the diagnosis of PCa. RESULTS: Among the total number of patients, 57 were confirmed with PCa (the positive group) and the other 154 with benign prostate conditions (the negative group) by biopsy pathology. The free PSA level (fPSA), free to total PSA ratio (f/tPSA) and PSEP content were dramatically lower in the positive than in the negative group (all P< 0.01). Uni- and multivariate analyses showed f/tPSA and PSEP to be independent factors for predicting PCa with the PSA gray zone and PI-RADS-3 lesions, with the AUC values of 0.70 and 0.78, best cutoff values of 0.18 and 1.45 µg/L, sensitivity of 84.21% and 70.18%, and specificity of 58.44% and 77.27%, respectively (P< 0.01). The multivariate model with combined use of f/tPSA and PSEP (AUC: 0.82, best cutoff value: 0.31, sensitivity: 82.46%, specificity: 75.32%) outperformed either f/tPSA or PSEP alone in the diagnosis of PCa with the PSA gray zone and PI-RADS-3 lesions (P< 0.01, P = 0.04). CONCLUSION: For patients with the PSA gray zone and PI-RADS-3 lesions, f/tPSA and PSEP are significant predictors of PCa. The multivariate model of PSEP combined with f/tPSA can replace f/tPSA in the detection of PCa to improve diagnostic performance and avoid unnecessary prostate biopsy.


Assuntos
Antígeno Prostático Específico , Próstata , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Antígeno Prostático Específico/sangue , Próstata/patologia , Próstata/diagnóstico por imagem , Exossomos , Imageamento por Ressonância Magnética , Sensibilidade e Especificidade , Idoso , Pessoa de Meia-Idade , Biópsia por Agulha , Relevância Clínica
9.
Org Lett ; 26(32): 6927-6932, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39106055

RESUMO

Herein is the first example of photocatalytic cross-coupling of alkenes with aldehydes by a single catalyst without an external photosensitizer and any additives. Irradiation of the aromatic aldehyde and cobaloxime catalyst results in the formation of an acyl radical, which undergoes radical addition with alkene or indole and subsequently ß-H elimination to afford alkenyl ketone. The reaction features cheap and readily available raw materials, a broad substrate scope, and mild conditions, even for late-stage derivatization of bioactive compounds.

10.
Sci Rep ; 14(1): 16607, 2024 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025927

RESUMO

Immune checkpoint inhibitors (ICI) have emerged as a promising therapeutic option for melanoma, which demonstrating improved clinical outcomes in melanoma patients regardless of specific genetic mutations. However, the identification of reliable biomarkers for predicting immunotherapy response and prognosis remains a challenge. In this study, we performed genetic profiling of the melanoma patients with different subtypes and evaluated the efficacy of ICI treatment. A total of 221 melanoma patients were included in our cohort, consisting primarily of acral lentiginous melanoma (ALM), cutaneous malignant melanoma (CMM), and mucosal malignant melanoma (MMM). Genetic analysis revealed BRAF mutations was predominant in CMM and NRAS mutations was prevalent in ALM. Copy number variants (CNVs) and structural variants (SV) were also detected, with CCND1 and CDK4 being the most affected genes in CNV and BRAF, ALK and RAF1 being the druggable targets in SV. Furthermore, NRAS mutations were associated with a poor prognosis in ALM, while TERT mutations were linked to unfavorable outcomes in CMM after receiving PD-1 therapy. Additionally, ALK expression exhibited improved outcomes in both ALM and CMM subtypes. Our study provides a comprehensive genomic and pathological profiling of Chinese melanoma patients, shedding light on the molecular landscape of the disease. Furthermore, numbers of gene mutations and ALK expression were identified as prognostic indicators. These findings contribute to the understanding of melanoma genetics in the Chinese population and have implications for personalized treatment approaches.


Assuntos
Imunoterapia , Melanoma , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , China , Variações do Número de Cópias de DNA , População do Leste Asiático/genética , GTP Fosfo-Hidrolases/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Melanoma/diagnóstico , Melanoma/tratamento farmacológico , Melanoma/genética , Proteínas de Membrana/genética , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética
11.
Eur J Immunol ; : e2350655, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973083

RESUMO

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

12.
Curr Med Chem ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38831674

RESUMO

Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.

13.
J Cancer Res Clin Oncol ; 150(6): 302, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856753

RESUMO

PURPOSE: Nowadays, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have been approved for treating metastatic breast cancer and have achieved inspiring curative effects. But some discoveries have indicated that CDK 4/6 are not the requisite factors in some cell types because CDK2 partly compensates for the inhibition of CDK4/6. Thus, it is urgent to design CDK2/4/6 inhibitors for significantly enhancing their potency. This study aims to explore the mechanism of the binding of CDK2/4/6 kinases and their inhibitors to design novel CDK2/4/6 inhibitors for significantly enhancing their potency in different kinds of cancers. MATERIALS AND METHODS: A series of 72 disparately functionalized 4-substituted N-phenylpyrimidin-2-amine derivatives exhibiting potent inhibitor activities against CDK2, CDK4 and CDK6 were collected to apply to this research. The total set of these derivatives was divided into a training set (54 compounds) and a test set (18 compounds). The derivatives were constructed through the sketch molecule module in SYBYL 6.9 software. A Powell gradient algorithm and Tripos force field were used to calculate the minimal structural energy and the minimized structure was used as the initial conformation for molecular docking. By the means of 3D-QSAR models, partial least squares (PLS) analysis, molecular dynamics (MD) simulations and binding free energy calculations, we can find the relationship between structure and biological activity. RESULTS: In this study, we used molecular docking, 3D-QSAR and molecular dynamics simulation methods to comprehensively analyze the interaction and structure-activity relationships of 72 new CDK2/4/6 inhibitors. We used detailed statistical data to reasonably verify the constructed 3D-QSAR models for three receptors (q2 of CDK2 = 0.714, R2pred = 0.764, q2 = 0.815; R2pred of CDK4 = 0.681, q2 = 0.757; R2pred of CDK6 = 0.674). MD simulations and decomposition energy analysis validated the reasonability of the docking results and identified polar interactions as crucial factors that influence the different bioactivities of the studied inhibitors of CDK2/4/6 receptors, especially the electrostatic interactions of Lys33/35/43 and Asp145/158/163. The nonpolar interaction with Ile10/12/19 was also critical for the differing potencies of the CDK2/4/6 inhibitors. We concluded that the following probably enhanced the bioactivity against CDK2/4/6 kinases: (1) electronegative groups at the N1-position and electropositive and moderate-sized groups at ring E; (2) electrogroups featured at R2; (3) carbon atoms at the X-position or ring C replaced by a benzene ring; and (4) an electrogroup as R4. CONCLUSION: Previous studies, to our knowledge, only utilized a single approach of 3D-QSAR and did not integrate this method with other sophisticated techniques such as molecular dynamics simulations to discover new potential inhibitors of CDK2, CDK4, or CDK6. So we applied the intergenerational technology, such as 3D-QSAR technology, molecular docking simulation techniques, molecular dynamics simulations and MMPBSA19/MMGBSA20-binding free energy calculations to statistically explore the correlations between the structure with biological activities. The constructed 3D-QSAR models of the three receptors were reasonable and confirmed by the excellent statistical data. We hope the results obtained from this work will provide some useful references for the development of novel CDK2/4/6 inhibitors.


Assuntos
Quinase 2 Dependente de Ciclina , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteínas Quinases , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/química , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/química , Humanos , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Quinase 2 Dependente de Ciclina/química , Pirimidinas/química , Pirimidinas/farmacologia , Relação Quantitativa Estrutura-Atividade
14.
Ann Thorac Med ; 19(2): 155-164, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766377

RESUMO

BACKGROUND: One-lung ventilation (OLV) is frequently applied during video-assisted thoracoscopic surgery (VATS) airway management to collapse and isolate the nondependent lung (NL). OLV can give rise to hypoxemia as a result of the pulmonary shunting produced. Our study aimed to assess the influence of continuous positive airway pressure (CPAP) combined with small-tidal-volume ventilation on improving arterial oxygenation and decreasing pulmonary shunt rate (QS/QT) without compromising surgical field exposure during OLV. METHODS: Forty-eight patients undergoing scheduled VATS lobectomy were enrolled in this research and allocated into three groups at random: C group (conventional ventilation, no NL ventilation intervention was performed), LP group (NL was ventilated with lower CPAP [2 cmH2O] and a 40-60 mL tidal volume [TV]), and HP group (NL was ventilated with higher CPAP [5 cmH2O] and a 60-80 mL TV). Record the blood gas analysis data and calculate the QS/QT at the following time: at the beginning of the OLV (T0), 30 min after OLV (T1), and 60 min after OLV (T2). Surgeons blinded to ventilation techniques were invited to evaluate the surgical fields. RESULTS: The demography data of the three groups were consistent with the surgical data. At T1, PaO2 in the HP group was substantially higher compared to the C group (P < 0.05), while there was no significant difference in the LP group (P > 0.05). At T1-T2, PaCO2 in the LP and HP groups was significantly less than that in the C group (P < 0.05). At T1, the QS/QT values of groups C, LP, and HP were 29.54 ± 6.89%, 22.66 ± 2.08%, and 19.64 ± 5.76%, respectively, and the QS/QT values in the LP and HP groups markedly reduced (P < 0.01). The surgical field's evaluation by the surgeon among the three groups was not notable (P > 0.05). CONCLUSION: CPAP combined with small-tidal-volume ventilation effectively improved arterial oxygenation and reduced QS/QT and PaCO2 without compromising surgical field exposure during OLV. Among them, 5 cmH2O CPAP + 60-80 ml TV ventilation had a better effect on improving oxygenation.

15.
Genes (Basel) ; 15(5)2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38790173

RESUMO

Alternanthera sessilis is considered the closest relative to the invasive weed Alternanthera philoxeroides in China, making it an important native species for studying the invasive mechanisms and adaptations of A. philoxeroides. Chloroplasts play a crucial role in a plant's environmental adaptation, with their genomes being pivotal in the evolution and adaptation of both invasive and related species. However, the chloroplast genome of A. sessilis has remained unknown until now. In this study, we sequenced and assembled the complete chloroplast genome of A. sessilis using high-throughput sequencing. The A. sessilis chloroplast genome is 151,935 base pairs long, comprising two inverted repeat regions, a large single copy region, and a small single copy region. This chloroplast genome contains 128 genes, including 8 rRNA-coding genes, 37 tRNA-coding genes, 4 pseudogenes, and 83 protein-coding genes. When compared to the chloroplast genome of the invasive weed A. philoxeroides and other Amaranthaceae species, we observed significant variations in the ccsA, ycf1, and ycf2 regions in the A. sessilis chloroplast genome. Moreover, two genes, ccsA and accD, were found to be undergoing rapid evolution due to positive selection pressure. The phylogenetic trees were constructed for the Amaranthaceae family, estimating the time of independent species formation between A. philoxeroides and A. sessilis to be approximately 3.5186-8.8242 million years ago. These findings provide a foundation for understanding the population variation within invasive species among the Alternanthera genus.


Assuntos
Amaranthaceae , Genoma de Cloroplastos , Espécies Introduzidas , Filogenia , Genoma de Cloroplastos/genética , Amaranthaceae/genética , Plantas Daninhas/genética , Cloroplastos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Evolução Molecular
16.
World J Clin Cases ; 12(11): 1990-1995, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38660553

RESUMO

BACKGROUND: When an anorectal foreign body is found, its composition and shape should be evaluated, and a timely and effective treatment plan should be developed based on the patient's symptoms to avoid serious complications such as intestinal perforation caused by displacement of the foreign body. CASE SUMMARY: A 54-year-old male was admitted to our outpatient clinic on June 3, 2023, due to a rectal foreign body that had been embedded for more than 24 h. The patient reported using a glass electrode tube to assist in the recovery of prolapsed hemorrhoids, however, the electrode tube was inadvertently inserted into the anus and could not be removed by the patient. During hospitalization, the patient underwent surgery, and the foreign body was dragged into the rectum with the aid of colonoscopy. The anus was dilated with a comb-type pulling hook and an anal fistula pulling hook to widen the anus and remove the foreign body, and the local anal symptoms were then relieved with topical drugs. The patient was allowed to eat and drink, and an entire abdominal Computed tomography (CT) and colonoscopy were reviewed 3 d after surgery. CT revealed no foreign body residue and colonoscopy showed no metal or other residues in the colon and rectum, and no apparent intestinal tract damage. CONCLUSION: The timeliness and rationality of the surgical and therapeutic options for this patient were based on a literature review of the clinical signs and conceivable conditions in such cases. The type, material and the potential risks of rectal foreign bodies should be considered.

17.
In Vitro Cell Dev Biol Anim ; 60(4): 374-381, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38592596

RESUMO

The purpose of this research was to investigate whether or not avicularin (AVL) possesses any anticancer properties when tested against lung cancer. In the beginning, the effect that it had on the cellular viability of A549 cells was investigated, and it was discovered that AVL has a considerable negative impact on cellular viability. Following that, an investigation using flow cytometry was carried out to investigate its function in the process of apoptosis and the cell cycle of A549 cells. It has been discovered that AVL significantly promotes apoptosis and stops the cell cycle at the G2/M phase. The colony-forming capacity of A549 cells was observed to be greatly suppressed as the AVL concentration increased compared to the group that received no treatment. In addition to this, the benzo(a)pyrene in vivo model was established in order to investigate the pharmacological value of AVL. The findings revealed that AVL greatly prevented the formation of pro-inflammatory cytokines, in addition to the reduction in oxidative stress, which was evidenced by a reduction in the concentration of TNF-α, IL-1ß, IL-6, and MDA with an improvement in the concentration of SOD and GPx, respectively. Our results successfully demonstrated the pharmacological benefit of avicularin against lung cancer, and it has been suggested that it showed a multifactorial effect.


Assuntos
Apoptose , Inflamação , Neoplasias Pulmonares , Estresse Oxidativo , Estresse Oxidativo/efeitos dos fármacos , Humanos , Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Animais , Inflamação/patologia , Inflamação/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Camundongos
18.
World J Clin Cases ; 12(8): 1481-1486, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38576802

RESUMO

BACKGROUND: In recent years, confocal laser endomicroscopy (CLE) has become a new endoscopic imaging technology at the microscopic level, which is extensively performed for real-time in vivo histological examination. CLE can be performed to distinguish benign from malignant lesions. In this study, we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma. CASE SUMMARY: A 63-year-old woman was diagnosed with gastric mucosal lesions, which may be gastric cancer, in the small curvature of the stomach by gastroscopy. She consented to undergo CLE for morphological observation of the gastric mucosa. Through the combination of CLE diagnosis and postoperative pathology, the intraoperative CLE diagnosis was considered to be reliable. According to our experience, CLE can be performed as the first choice for the diagnosis of gastric cancer. CONCLUSION: CLE has several advantages over pathological diagnosis. We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.

19.
Clin Transl Oncol ; 26(8): 2020-2024, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38478261

RESUMO

OBJECTIVE: The primary goal of this study was to investigate the expressions of TUFT1 (Tuftelin) and Rac1-GTP in the cancerous tissues of individuals with triple-negative breast cancer (TNBC). Additionally, we aimed to explore the correlation between TUFT1 and Rac1-GTP expressions and examine the associations of TUFT1 and Rac1-GTP expressions with the clinical and pathological indicators of the patients. METHODS: Ninety-six patients diagnosed with TNBC, scheduled for surgery between May 2022 and November 2022, were enrolled in this study. Cancerous tissue specimens were collected from these patients, and immunohistochemistry was employed to evaluate the levels of TUFT1 and Rac1-GTP expressions in the cancerous tissues. Subsequent to data collection, a comprehensive analysis was conducted to examine the correlation between TUFT1 and Rac1-GTP expressions. Furthermore, we sought to assess the associations of TUFT1 and Rac1-GTP expressions with the clinical and pathological indicators of the patients. RESULTS: The TUFT1 protein was expressed in both the membrane and cytoplasm of TNBC cancer cells, with notably higher expression observed in the cytoplasm. Rac1-GTP was primarily expressed in the cytoplasm. There was a positive correlation between the levels of TUFT1 and Rac1-GTP expressions (χ2 = 9.816, P < 0.05). The levels of TUFT1 and Rac1-GTP protein expressions showed no correlation with patient age (χ2 = 2.590, 2.565, P > 0.05); however, they demonstrated a positive correlation with tumor size (χ2 = 5.592,5.118), histological grading (χ2 = 6.730, 5.443), and lymph node metastasis (χ2 = 8.221, 5.180) (all with a significance level of P < 0.05). CONCLUSION: A significant correlation was identified between the levels of TUFT1 and Rac1-GTP expressions in the cancerous tissues of patients with TNBC, suggesting a close association with the progression of TNBC. The two molecules play significant roles in facilitating an early diagnosis and treatment of TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Proteínas rac1 de Ligação ao GTP , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Metástase Linfática , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica , Citoplasma/metabolismo
20.
Materials (Basel) ; 17(4)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38399170

RESUMO

Uniaxial cyclic compression tests were performed to investigate the compression deformation and damage of polymer-bonded explosive (PBX) simulant, particularly shear localization. The macroscopic mechanical behavior and mesoscale failure mechanisms of the PBX simulant were analyzed by optical observation and SEM scanning methods. After each cyclic compression, the specimen was scanned by X-ray computed tomography (CT), and the internal 3D deformation of the specimen was calculated using the digital volume correlation (DVC) method. The results show that the stress-strain curve of the PBX simulant exhibits five stages and coincides with the morphological changes on the surface of the specimen. The mesoscale failure mechanism is dominated by particle interface debonding and binder tearing, accompanied by a small amount of particle breakage. There are three bifurcation points (T1, T2, and T3) in the curves of the normal and shear strain components with compression strain. It was found that these bifurcation points can reflect the full progression of the specimen from inconspicuous damage to uniformly distributed damage, shear localization, and eventual macroscopic fracture. The strain invariant I1 can quantitatively and completely characterize the deformation and damage processes of the PBX simulant under cyclic compression.

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