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1.
Ecotoxicol Environ Saf ; 278: 116400, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38718725

RESUMO

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

2.
Anal Chim Acta ; 1304: 342518, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38637045

RESUMO

BACKGROUND: Surface-enhanced Raman scattering (SERS) technology have unique advantages of rapid, simple, and highly sensitive in the detection of serum, it can be used for the detection of liver cancer. However, some protein biomarkers in body fluids are often present at ultra-low concentrations and severely interfered with by the high-abundance proteins (HAPs), which will affect the detection of specificity and accuracy in cancer screening based on the SERS immunoassay. Clearly, there is a need for an unlabeled SERS method based on low abundance proteins, which is rapid, noninvasive, and capable of high precision detection and screening of liver cancer. RESULTS: Serum samples were collected from 60 patients with liver cancer (27 patients with stage T1 and T2 liver cancer, 33 patients with stage T3 and T4 liver cancer) and 40 healthy volunteers. Herein, immunoglobulin and albumin were separated by immune sorption and Cohn ethanol fractionation. Then, the low abundance protein (LAPs) was enriched, and high-quality SERS spectral signals were detected and obtained. Finally, combined with the principal component analysis-linear discriminant analysis (PCA-LDA) algorithm, the SERS spectrum of early liver cancer (T1-T2) and advanced liver cancer (T3-T4) could be well distinguished from normal people, and the accuracy rate was 98.5% and 100%, respectively. Moreover, SERS technology based on serum LAPs extraction combined with the partial least square-support vector machine (PLS-SVM) successfully realized the classification and prediction of normal volunteers and liver cancer patients with different tumor (T) stages, and the diagnostic accuracy of PLS-SVM reached 87.5% in the unknown testing set. SIGNIFICANCE: The experimental results show that the serum LAPs SERS detection combined with multivariate statistical algorithms can be used for effectively distinguishing liver cancer patients from healthy volunteers, and even achieved the screening of early liver cancer with high accuracy (T1 and T2 stage). These results showed that serum LAPs SERS detection combined with a multivariate statistical diagnostic algorithm has certain application potential in early cancer screening.


Assuntos
Proteínas Sanguíneas , Neoplasias Hepáticas , Humanos , Análise Discriminante , Biomarcadores , Neoplasias Hepáticas/diagnóstico , Análise Espectral Raman/métodos , Análise de Componente Principal
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 302-307, 2024 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-38557384

RESUMO

Central precocious puberty (CPP) is a developmental disorder caused by early activation of the hypothalamic-pituitary-gonadal axis. The incidence of CPP is rapidly increasing, but the underlying mechanisms are not fully understood. Previous studies have shown that gain-of-function mutations in the KISS1R and KISS1 genes and loss-of-function mutations in the MKRN3, LIN28, and DLK1 genes may lead to early initiation of pubertal development. Recent research has also revealed the significant role of epigenetic factors such as DNA methylation and microRNAs in the regulation of gonadotropin-releasing hormone neurons, as well as the modulating effect of gene networks involving multiple variant genes on pubertal initiation. This review summarizes the genetic etiology and pathogenic mechanisms underlying CPP.


Assuntos
MicroRNAs , Puberdade Precoce , Humanos , Puberdade Precoce/genética , Hormônio Liberador de Gonadotropina/genética , Mutação , Puberdade/genética , Ubiquitina-Proteína Ligases/genética
4.
ACS Appl Mater Interfaces ; 16(14): 17393-17400, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38563348

RESUMO

We report the electrochemical potential dependence of photocatalysis produced by hot electrons in plasmon-resonant grating structures. Here, corrugated metal surfaces with a period of 520 nm are illuminated with 785 nm wavelength laser light swept as a function of incident angle. At incident angles corresponding to plasmon-resonant excitation, we observe sharp peaks in the electrochemical photocurrent and dips in the photoreflectance consistent with the conditions under which there is wavevector matching between the incident light and the spacing between the lines in the grating. In addition to the bare plasmonic metal surface (i.e., Au), which is catalytically inert, we have measured grating structures with a thin layer of Pt, Ru, and Ni catalyst coatings. For the bare Au grating, we observe that the plasmon-resonant photocurrent remains relatively featureless over the applied potential range from -0.8 to +1.2 V vs NHE. For the Pt-coated grating, we observe a sharp peak around -0.3 V vs NHE, three times larger than the bare Au grating, and near complete suppression of the oxidation half-reaction, reflecting the reducing nature of Pt as a good hydrogen evolution reaction catalyst. The photocurrent associated with the Pt-coated grating is less noisy and produces higher photocurrents than the bare Au grating due to the faster kinetics (i.e., charge transfer) associated with the Pt-coated surface. The plasmon-resonant grating structures enable us to compare plasmon-resonant excitation with that of bulk metal interband absorption simply by rotating the polarization of the light while leaving all other parameters of the experiment fixed (i.e., wavelength, potential, electrochemical solution, sample surface, etc.). A 64X plasmon-resonant enhancement (i.e., p-to-s polarized photocurrent ratio) is observed for the Pt-coated grating compared to 28X for the bare grating. The nickel-coated grating shows an increase in the hot-electron photocurrent enhancement in both oxidation and reduction half-reactions. Similarly, Ru-coated gratings show an increase in hot-electron photocurrents in the oxidation half-reaction compared to the bare Au grating. Plasmon-resonant enhancement factors of 36X and 15X are observed in the p-to-s polarized photocurrent ratio for the Ni and Ru gratings, respectively.

5.
Eur J Oncol Nurs ; 70: 102550, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38554614

RESUMO

PURPOSE: A systematic review investigated the effectiveness of physical activity in alleviating lower limb lymphedema among patients with gynecological cancer after surgery. METHODS: A systematic review of randomized controlled trials and quasi-experimental designs was conducted. Six databases, Cinahl, Cochrane, Embase, Medline, Scopus, and Web of Science, were searched for relevant publications from inception to October 2022 and updated in January 2024. RevMan software was used to perform meta-analysis using a random-effects model. RESULTS: Seven studies (5 randomized controlled trials) containing 261 subjects were synthesized. The risk of bias was low in the included studies. The exercise interventions for lower limb lymphedema included active, aerobic, aquatic, and weight-lifting exercises. Meta-analyses showed that active exercise had no effect on lymphedema symptoms of limb volume, pain, and heaviness. However, the effectiveness of exercise on limb volume had subthreshold borderline significance in 2 studies (standardized mean difference = 0.43, 95% confidence interval - 0.01, 0.88; I2 = 0%, p = 0.06). Three studies found that lymphedema symptoms were significantly improved after exercise interventions. The adherence rate of the exercise was 77-100%, with the only complication being cellulitis. CONCLUSIONS: Although the meta-analysis does not reveal a significant effect, the systematic review study demonstrated that exercise is feasible, safe, and has a clinical effect on alleviating lymphedema-related symptoms of women following gynecological cancer surgery.

6.
Signal Transduct Target Ther ; 9(1): 74, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528022

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts the epithelial barrier and triggers airway inflammation. The envelope (E) protein, a core virulence structural component of coronaviruses, may play a role in this process. Pathogens could interfere with transepithelial Cl- transport via impairment of the cystic fibrosis transmembrane conductance regulator (CFTR), which modulates nuclear factor κB (NF-κB) signaling. However, the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function, Cl- transport and the robust inflammatory response remain to be elucidated. Here, we have demonstrated that E protein down-regulated the expression of tight junctional proteins, leading to the disruption of the airway epithelial barrier. In addition, E protein triggered the activation of Toll-like receptor (TLR) 2/4 and downstream c-Jun N-terminal kinase (JNK) signaling, resulting in an increased intracellular Cl- concentration ([Cl-]i) via up-regulating phosphodiesterase 4D (PDE4D) expression in airway epithelial cells. This elevated [Cl-]i contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1 (SGK1). Moreover, blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein. Overall, these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/genética , COVID-19/metabolismo , Inflamação/genética , Inflamação/metabolismo , Transdução de Sinais , Células Epiteliais/metabolismo , Glucocorticoides
7.
Aging Clin Exp Res ; 36(1): 71, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485798

RESUMO

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Obstrução do Colo da Bexiga Urinária , Masculino , Humanos , Hiperplasia Prostática/cirurgia , Nomogramas , Estudos Retrospectivos , Obstrução do Colo da Bexiga Urinária/cirurgia
8.
Front Cardiovasc Med ; 11: 1335552, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545347

RESUMO

Background: This study aims to analyze the risk factors associated with prolonged mechanical ventilation (PMV) in patients following surgical treatment for acute type A aortic dissection (ATAAD). The objectives include constructing a predictive model for risk assessment and validating its predictive efficacy. Methods: A total of 452 patients diagnosed with ATAAD and undergoing surgical procedures at a tertiary hospital in Nanjing between January 2021 and April 2023 were selected using a convenience sampling method. Patients were categorized into two groups: PMV group (n = 132) and non-PMV group (n = 320) based on the occurrence of prolonged mechanical ventilation (PMV), and their clinical data were compared. The data were randomly divided into a modeling set and a validation set in a 7:3 ratio. Risk factors for PMV were identified in the modeling group using logistic regression analysis. A risk prediction model was constructed using R 4.1.3 software, visualized via a column chart. Receiver Operating Characteristic (ROC) curves were generated using the validation set to assess model differentiation. Calibration curves were plotted to evaluate accuracy and consistency, and Decision Curve Analysis (DCA) was applied to evaluate clinical utility. Results: The logistic regression analysis identified age, body mass index, preoperative white blood cell count, preoperative creatinine, preoperative cerebral hypoperfusion, and cardiopulmonary bypass time as significant risk factors for postoperative PMV in patients with ATAAD. The area under the curve (AUC) for the validation set ROC curve was 0.856, 95% confidence interval (0.805-0.907), indicating good discrimination. Calibration curves revealed strong alignment with the ideal curve, and the Hosmer-Lemeshow goodness-of-fit test indicated a well-fitted model (P = 0.892). The DCA curve demonstrated a high net benefit value, highlighting the model's strong clinical utility. Conclusions: The risk prediction model developed in this study for PMV in patients undergoing surgery for ATAAD exhibits robust predictive performance. It provides valuable insights for healthcare practitioners in predicting the likelihood of PMV and devising timely and personalized intervention strategies.

9.
Acad Radiol ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38458887

RESUMO

BACKGROUND: Gliomas are the most common primary brain tumours and constitute approximately half of all malignant glioblastomas. Unfortunately, patients diagnosed with malignant glioblastomas typically survive for less than a year. In light of this circumstance, genotyping is an effective means of categorising gliomas. The Ki67 proliferation index, a widely used marker of cellular proliferation in clinical contexts, has demonstrated potential for predicting tumour classification and prognosis. In particular, magnetic resonance imaging (MRI) plays a vital role in the diagnosis of brain tumours. Using MRI to extract glioma-related features and construct a machine learning model offers a viable avenue to classify and predict the level of Ki67 expression. METHODS: This study retrospectively collected MRI data and postoperative immunohistochemical results from 613 glioma patients from the First Affliated Hospital of Nanjing Medical University. Subsequently, we performed registration and skull stripping on the four MRI modalities: T1-weighted (T1), T2-weighted (T2), T1-weighted with contrast enhancement (T1CE), and Fluid Attenuated Inversion Recovery (FLAIR). Each modality's segmentation yielded three distinct tumour regions. Following segmentation, a comprehensive set of features encompassing texture, first-order, and shape attributes were extracted from these delineated regions. Feature selection was conducted using the least absolute shrinkage and selection operator (LASSO) algorithm with subsequent sorting to identify the most important features. These selected features were further analysed using correlation analysis to finalise the selection for machine learning model development. Eight models: logistic regression (LR), naive bayes, decision tree, gradient boosting tree, and support vector classification (SVM), random forest (RF), XGBoost, and LightGBM were used to objectively classify Ki67 expression. RESULTS: In total, 613 patients were enroled in the study, and 24,455 radiomic features were extracted from each patient's MRI. These features were eventually reduced to 36 after LASSO screening, RF importance ranking, and correlation analysis. Among all the tested machine learning models, LR and linear SVM exhibited superior performance. LR achieved the highest area under the curve score of 0.912 ± 0.036, while linear SVM obtained the top accuracy with a score of 0.884 ± 0.031. CONCLUSION: This study introduced a novel approach for classifying Ki67 expression levels using MRI, which has been proven to be highly effective. With the LR model at its core, our method demonstrated its potential in signalling a promising avenue for future research. This innovative approach of predicting Ki67 expression based on MRI features not only enhances our understanding of cell activity but also represents a significant leap forward in brain glioma research. This underscores the potential of integrating machine learning with medical imaging to aid in the diagnosis and prognosis of complex diseases.

10.
Vet Microbiol ; 291: 110013, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38364468

RESUMO

Potassium diformate (KDF) is a kind of formate, which possesses the advantages of antimicrobial activity, growth promotion and preventing diarrhea in weaned piglets. However, the researches of KDF in animal production mostly focused on apparent indexes such as growth performance and the mechanisms of KDF on intestinal health have not been reported. Thus, porcine small intestinal epithelial cells (IPEC-J2) infected with Enterohemorrhagic Escherichia coli (EHEC) was used to investigate the role of KDF on alleviating intestinal inflammation in this study. The 0.125 mg/mL KDF treated IPEC-J2 cells for 6 h and IPEC-J2 cells challenged with 5 × 107 CFU/mL EHEC for 4 h were confirmed as the optimum concentration and time for the following experiment. The subsequent experiment was divided into four groups: control group (CON), EHEC group, KDF group, KDF+EHEC group. The results showed that KDF increased the cell viability and the gene expression levels of SGLT3 and TGF-ß, while decreased the content of IL-1ß compared with the CON group. The cell viability and the gene expressions of SGLT1, SGLT3, GLUT2, Claudin-1, Occludin and TGF-ß, and the protein expression of ZO-1 in EHEC group were lower than those in CON group, whereas the gene expressions of IL-1ß, TNF, IL-8 and TLR4, and the level of phosphorylation NF-кB protein were increased. Pretreatment with KDF reduced the content of IgM and IL-1ß, the gene expressions of IL-1ß, TNF, IL-8 and TLR4 and the level of phosphorylation NF-кB protein, and increased the gene expression of TGF-ß and the protein expression of Occludin in IPEC-J2 cells infected EHEC. In conclusion, 0.125 mg/mL KDF on IPEC-J2 cells for 6 h had the beneficial effects on ameliorating the intestinal inflammation because of reduced pro-inflammatory cytokines and enhanced anti-inflammatory cytokines through regulating NF-кB signaling pathway under the EHEC challenge.


Assuntos
Escherichia coli Êntero-Hemorrágica , Doenças dos Suínos , Animais , Suínos , Ocludina/genética , Ocludina/metabolismo , Escherichia coli Êntero-Hemorrágica/metabolismo , Interleucina-8/metabolismo , NF-kappa B/metabolismo , Receptor 4 Toll-Like , Linhagem Celular , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/veterinária , Citocinas/genética , Citocinas/metabolismo , Células Epiteliais/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Mucosa Intestinal , Doenças dos Suínos/tratamento farmacológico , Doenças dos Suínos/metabolismo
12.
Plant Physiol Biochem ; 207: 108326, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38237421

RESUMO

Understanding how to adapt outdoor cultures of Nannochloropsis oceanica to high light (HL) is vital for boosting productivity. The N. oceanica RB2 mutant, obtained via ethyl methanesulfonate mutagenesis, was chosen for its tolerance to Rose Bengal (RB), a singlet oxygen (1O2) generator. Compared to the wild type (WT), the RB2 mutant showed higher resilience to excess light conditions. Analyzing the ascorbate-glutathione cycle (AGC), involving ascorbate peroxidases (APX, EC 1.11.1.11), dehydroascorbate reductase (DHAR, EC 1.8.5.1), and glutathione reductase (GR, EC 1.8.1.7), in the RB2 mutant under HL stress provided valuable insights. At 250 µmol photon m-2 s-1 (HL), the WT strain displayed superoxide anion radicals (O2▪-) and hydrogen peroxide (H2O2) accumulation, increased lipid peroxidation, and cell death compared to normal light (NL) conditions (50 µmol photon m-2 s-1). The RB2 mutant didn't accumulate O2▪- and H2O2 after HL exposure, and exhibited increased APX, DHAR, and GR activities and transcript levels compared to WT and remained consistent after HL treatment. Although the RB2 mutant had a smaller ascorbate (AsA) pool than the WT, its ability to regenerate dehydroascorbate (DHA) increased post HL exposure, indicated by a higher AsA/DHA ratio. Additionally, under HL conditions, the RB2 mutant displayed an improved glutathione (GSH) regeneration rate (GSH/GSSG ratio) without changing the GSH pool size. Remarkably, H2O2 or menadione (a O2▪- donor) treatment induced cell death in the WT strain but not in the RB2 mutant. These findings emphasize the essential role of AGC in the RB2 mutant of Nannochloropsis in handling photo-oxidative stress.


Assuntos
Peróxido de Hidrogênio , Rosa Bengala , Peróxido de Hidrogênio/metabolismo , Ácido Ascórbico/metabolismo , Antioxidantes/metabolismo , Glutationa Redutase/metabolismo , Estresse Oxidativo , Glutationa/metabolismo , Aclimatação , Ascorbato Peroxidases/genética , Ascorbato Peroxidases/metabolismo
13.
Am Surg ; : 31348241227202, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38214585

RESUMO

PURPOSE: This study aimed to investigate the prognostic value of alpha-fetoprotein (AFP) ratio in patients with AFP-negative hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We retrospectively analyzed 600 AFP-negative HCC patients who underwent hepatectomy. The AFP ratio was calculated as the ratio of AFP level 1 week before surgery to the level 20-40 days after hepatectomy. Immunohistochemistry assay was used to assess protein expression in HCC tissue. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). RESULTS: The study found that a cutoff value of 1.6 ng/ml for AFP ratio, determined using X-tile software, was optimal for predicting prognosis. Patients with a high AFP ratio had a worse prognosis compare to those with a low AFP ratio (DFS, P = .026; OS, P = .034). Patients with a high AFP ratio had a worse prognosis compared to those with a low AFP ratio. Multivariate analysis revealed that AFP ratio >1.6, negative HepPar-1 expression, and vascular invasion were independent predictors of both DFS and OS. Vascular invasion had a higher area under the curve (AUC) than AFP ratio and HepPar-1 expression in predicting recurrence and death. The combination of AFP ratio, HepPar-1 expression, and vascular invasion provided better predictive accuracy for DFS and OS. CONCLUSION: The AFP ratio is a potential prognostic marker for AFP-negative HCC patients after hepatectomy. Combining the analysis of AFP ratio with HepPar-1 expression and vascular invasion can enhance the accuracy of predicting prognosis in these patients.

15.
ACS Nano ; 18(6): 4796-4810, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38261783

RESUMO

Telomeres are nanoscale DNA-protein complexes to protect and stabilize chromosomes. The reexpression of telomerase in cancer cells is a key determinant crucial for the infinite proliferation and long-term survival of most cancer cells. However, the use of telomerase inhibitors for cancer treatment may cause problems such as poor specificity, drug resistance, and cytotoxicity. Here, we discovered a nondrug and noninvasive terahertz modulation strategy capable of the long-term suppression of cancer cells by inhibiting telomerase activity. First, we found that an optimized frequency of 33 THz photon irradiation effectively inhibited the telomerase activity by molecular dynamics simulation and frequency filtering experiments. Moreover, in vitro experiments showed that telomerase activity in 4T1 and MCF-7 cells significantly decreased by 77% and 80% respectively, after 21 days of regular 33 THz irradiation. Furthermore, two kinds of cells were found to undergo aging, apoptosis, and DNA double-strand breaks caused by telomere crisis, which seriously affected the survival of cancer cells. In addition, the tumorigenicity of 4T1 cells irradiated with 33 THz waves for 21 days in in vivo mice decreased by 70%. In summary, this study demonstrates the potential application of THz modulation in nano therapy for cancer.


Assuntos
Neoplasias , Telomerase , Animais , Camundongos , Telomerase/metabolismo , Inibidores Enzimáticos/farmacologia , Telômero , Apoptose , DNA
16.
Phytomedicine ; 124: 155255, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181528

RESUMO

BACKGROUND: The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4+T cells response are related to its suppression of M1 macrophage still unclear. PURPOSE: The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4+T cells are related to exosome derived from M1-macrophage (M1-exo). STUDY-DESIGN/METHODS: Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets. Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4+ T cells to examine whether BBR inhibits CD4+T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4+T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4+T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP. RESULT: BBR reinstates CD4+ T cell homeostasis and reduces miR155 levels in both M1-exo and CD4+ T cells obtained from mice with CIA. In vitro, we found exosomes are indispensable for M1-CM on T lymphocyte activation and differentiation. BBR reversed M1-exo facilitating the activation and differentiation of CD4+T cells. Furthermore, BBR reversed glycolysis reprogramming of CD4+T cells induced by M1-exo, while these regulation effects were significantly weakened by miR155 mimic. CONCLUSION: The delivery of miR-155 by M1-exo contributes to CD4+ T cell immunometabolism dysfunction, a process implicated in the development of RA. The anti-arthritic effect of BBR is associated with the suppression of glycolysis and the disruption of CD4+ T cell subsets balance, achieved by reducing the transfer of M1-exo-miR155 into T cells.


Assuntos
Artrite Experimental , Artrite Reumatoide , Berberina , MicroRNAs , Animais , Camundongos , Ratos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Berberina/farmacologia , Linfócitos T CD4-Positivos , Modelos Animais de Doenças , Macrófagos , MicroRNAs/metabolismo
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123747, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38091653

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant tumor in head and neck. Early diagnosis can effectively improve the survival rate of patients. Nasopharyngeal exfoliative cytology, as a convenient and noninvasive auxiliary diagnostic method, is suitable for the population screening of NPC, but its diagnostic sensitivity is low. In this study, an electroporation-based SERS technique was proposed to detect and screen the clinical nasopharyngeal exfoliated cell samples. Firstly, nasopharyngeal swabs was used to collected the nasopharyngeal exfoliated cell samples from NPC patients (n = 54) and healthy volunteers (n = 60). Then, gold nanoparticles, as the Raman scattering enhancing substrates, were rapidly introduced into cells by electroporation technique for surface-enhanced Raman scattering (SERS) detection. Finally, SERS spectra combined with principal component analysis (PCA) and linear discriminant analysis (LDA) were employed to diagnose and distinguish NPC cell samples. Raman peak assignments combined with spectral differences reflected the biochemical changes associated with NPC, including nucleic acid, amino acid and carbohydrates. Based on the PCA-LDA approach, the sensitivity, specificity and accuracy of 98.15 %, 96.67 % and 97.37 %, respectively, were achieved for screening NPC. This study offers valuable assistance for noninvasive NPC auxiliary diagnosis, and has grate potential in expanding the application of the SERS technique in clinical cell sample testing.


Assuntos
Nanopartículas Metálicas , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/química , Neoplasias Nasofaríngeas/patologia , Ouro/química , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , Análise Discriminante , Eletroporação , Análise de Componente Principal
18.
Int J Gynecol Pathol ; 43(3): 284-289, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38085958

RESUMO

Carcinosarcoma (CS) is an aggressive form of gynecologic malignancy that accounts for ~5% of carcinomas in the endometrium and ovaries. There has been no significant improvement in survival over the last decades despite additional treatment options. PReferentially Expressed Antigen in MElanoma (PRAME) is an immunotherapy target used for the treatment of several solid tumors. We explored the PRAME protein expression levels in ovarian and uterine CS (n = 29). The expression levels were recorded by H-score (percentage of positively stained cells multiplied by staining intensity) in carcinomatous and sarcomatous components separately and compared by paired t-test. The marker expression levels of ovarian and uterine CS were tested against each other in the CS group. Sarcoma-predominant samples (>50% of the sampled tissue) were compared with samples without predominant sarcomatous components by a 2-sample pooled t-test. In addition, high-grade carcinomatous components of CS samples were tested against low-grade endometrioid carcinoma (International Federation of Gynecology and Obstetrics grades 1 and 2; n = 13), and sarcomatous components against uterine leiomyosarcoma (n = 14). There was no significant difference between any subgroups except for sarcomatous elements of CS and leiomyosarcoma ( P < 0.001). A weak positive correlation was found between H-scores of carcinomatous and sarcomatous components ( P = 0.062, r = 0.36). In the ovarian CS group, there was a moderate inverse correlation between age and the mean H-score of the carcinomatous component ( r = -0.683, P = 0.02). Our results further support PRAME overexpression in gynecologic cancers, including CS with similar expression levels in epithelial and mesenchymal components. PRAME might have a role in epithelial-mesenchymal transition in this group of cancers.

19.
Dev Comp Immunol ; 154: 105125, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38158145

RESUMO

Hirudo nipponia, a blood-sucking leech native to East Asia, possesses a rich repertoire of active ingredients in its saliva, showcasing significant medical potential due to its anticoagulant, anti-inflammatory, and antibacterial effects against human diseases. Despite previous studies on the transcriptomic and proteomic characteristics of leech saliva, which have identified medicinal compounds, our knowledge of tissue-specific transcriptomes and their spatial expression patterns remains incomplete. In this study, we conducted an extensive transcriptomic profiling of the salivary gland tissue in H. nipponia based on de novo assemblies of tissue-specific transcriptomes from the salivary gland, teeth, and general head region. Through gene ontology (GO) analysis and hierarchical clustering, we discovered a novel set of anti-coagulant factors-i.e., Hni-Antistasin, Hni-Ghilanten, Hni-Bdellin, Hni-Hirudin-as well as a previously unrecognized immune-related gene, Hni-GLIPR1 and uncharacterized salivary gland specific transcripts. By employing in situ hybridization, we provided the first visualization of gene expression sites within the salivary gland of H. nipponia. Our findings expand on our understanding of transcripts specifically expressed in the salivary gland of blood-sucking leeches, offering valuable resources for the exploration of previously unidentified substances with medicinal applications.


Assuntos
Hirudo medicinalis , Sanguessugas , Animais , Perfilação da Expressão Gênica , Hirudo medicinalis/genética , Hirudo medicinalis/metabolismo , Sanguessugas/genética , Sanguessugas/metabolismo , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Proteínas do Tecido Nervoso/genética , Proteômica , Glândulas Salivares/metabolismo
20.
World J Gastroenterol ; 29(42): 5781-5799, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38075850

RESUMO

BACKGROUND: As an emerging potential risk factor for gastric cancer, autoimmune gastritis (AIG) has garnered increasing attention from researchers. AIM: To analyze the research overview and popular topics in the field of AIG using bibliometrics. METHODS: Relevant publications on AIG in the Web of Science Core Collection were collated, and data visualization and analysis of the number of publications, countries, institutions, journals, authors, keywords, and citations were performed using software such as VOSviewer, CiteSpace, and Scimago Graphic. RESULTS: In total, 316 relevant articles were included in the analysis. From 2015 to 2022, the number of publications increased annually. The countries, institutions, authors, and journals with the highest number of publications in this field were Italy, Monash University, Toh BH, and Internal Medicine. The main keywords used in this field of research were pathogenesis, Helicobacter pylori, autoantibody, parietal cell antibody, atrophic gastritis, classification, diagnosis, autoimmune disease, risk, cancer, gastric cancer, vitamin B12 deficiency, and pernicious anemia. The following directions may be popular for future research: (1) The role of Helicobacter pylori in the pathogenesis of AIG; (2) diagnostic criteria for AIG and reference values for serum antibodies; (3) comorbidity mechanisms between AIG and other autoimmune diseases; (4) specific risks of AIG complicating gastric and other cancers; and (5) the role of vitamin B12 supplementation in patients with early-stage AIG. CONCLUSION: This bibliometric analysis reported on popular topics and emerging trends in AIG, with diagnosis and prognosis being research hotspots in this field.


Assuntos
Doenças Autoimunes , Gastrite Atrófica , Gastrite , Neoplasias Gástricas , Humanos , Autoanticorpos , Bibliometria , Gastrite/epidemiologia , Gastrite/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/complicações
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