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1.
J Environ Manage ; 365: 121600, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38963957

RESUMO

Electrolytic manganese residue (EMR) is known for high concentrations of Mn2+, NH4+, and heavy metals. Failure to undergo benign treatment and landfill disposal would undeniably lead to negative impacts on the quality of the surrounding ecological environment. This study sought to mitigate the latent environmental risks associated with EMR using a cooperative solidification/stabilization (S/S) method involving coal fly ash (CFA). Leveraging leaching toxicity tests, the leaching behavior of pollutants in electrolytic manganese residue-based geopolymer materials (EMRGM) was determined. At the same time, mechanistic insights into S/S processes were explored utilizing characterization techniques such as XRF, XRD, FT-IR, SEM-EDS, and XPS. Those results confirmed significant reductions in the leaching toxicities of Mn2+ and NH4+ to 4.64 µg/L and 0.99 mg/L, respectively, with all other heavy metal ions falling within the permissible limits set by relevant standards. Further analysis shows that most of NH4+ volatilizes into the air as NH3, and a small part is fixed in the EMRGM in the form of struvite; in addition to being oxidized to MnOOH and MnO2, Mn2+ will also be adsorbed and wrapped by silicon-aluminum gel together with other heavy metal elements in the form of ions or precipitation. This research undeniably provides a solid theoretical foundation for the benign treatment and resourceful utilization of EMR and CFA, two prominent industrial solid wastes.

2.
J Adolesc ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961794

RESUMO

INTRODUCTION: Subjective well-being, an important index for measuring mental health, is presently declining among junior high school students. Envy, one of their common emotions, is inextricably linked to subjective well-being. Based on the Dual Envy Theory, our research explores the bidirectional relationship between benign-malicious envy and subjective well-being. The mediating role of self-esteem, as well as the related gender differences, is examined. METHODS: Chinese middle school students (n = 1566, boys 50.3%, age = 13.96 ± 0.88 years old) were assessed at two time points over a 3-month interval. Structural equation modeling was used to examine the longitudinal relationships among the variables. RESULTS: (1) Cross-lagged analysis showed a positive bidirectional relationship between benign envy and subjective well-being and a negative bidirectional relationship between malicious envy and subjective well-being in the total sample. However, the path from T1 subjective well-being to T2 malicious envy in boys was not significant. (2) Self-esteem mediated the relationship between both benign and malicious envy and subjective well-being among both boys and girls. A Wald chi-square test showed that T2 self-esteem was a stronger predictor of T2 benign envy in boys than in girls. CONCLUSION: The results reveal a virtuous cycle of benign envy and subjective well-being, and a vicious cycle of malicious envy and subjective well-being, while emphasizing the role of self-esteem in this process. Gender differences were also noted. These findings have important implications for improving the subjective well-being of secondary school students and exploring the positive effects of envy.

3.
Fish Shellfish Immunol ; : 109752, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38977112

RESUMO

Pseudomonas plecoglossicida is a vital pathogen that poses a substantial risk to aquaculture. Small RNAs (sRNAs) are non-coding regulatory molecules capable of sensing environmental changes and modulating virulence-associated signaling pathways, such as the assembly of flagella. However, the relevant researches on P. plecoglossicida are an urgent need. Here, we report a novel sRNA, sRNA562, which has potential to regulate the post-transcriptional of fliP, a key component of the lateral flagellar type III secretion system. In this study, the effects of sRNA562 on the virulence of P. plecoglossicida and its role in regulating the pathogenic process were investigated through the use of a constructed sRNA562 deletion strain. The deletion of sRNA562 resulted in an up-regulation of fliP in P. plecoglossicida, and leading to increased swarming motility and enhanced the ability of biofilm formation, adhesion and chemotaxis. Subsequent artificial infection experiment demonstrated that the deletion of sRNA562 increased the virulence of P. plecoglossicida towards hybrid grouper, as evidenced by a reduction in survival rate, elevation of tissue bacterial load, and the exacerbation of histopathological damage. Further studies have found that the deletion of sRNA562 lead to an up-regulation of fliP expression during hybrid grouper infection, thereby enhancing bacterial swarming ability and ultimately heightening pathogenicity, leading to a dysregulated host response to infection, tissue damage and eventually death. Our work revealed a sRNA that exerts negative regulation on the expression of lateral flagella in P. plecoglossicida, thereby impacting its virulence. These findings provide a new perspective on the virulence regulation mechanism of P. plecoglossicida, contributing to a more comprehensive understanding in the field of pathogenicity research.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38980655

RESUMO

The vertebral artery's morphological characteristics are crucial in spontaneous vertebral artery dissection (sVAD). We aimed to investigate morphologic features related to ischemic stroke (IS) and develop a novel prediction model. Out of 126 patients, 93 were finally analyzed. We constructed 3D models and morphological analyses. Patients were randomly classified into training and validation cohorts (3:1 ratio). Variables selected by LASSO - including five morphological features and five clinical characteristics - were used to develop prediction model in the training cohort. The model exhibited a high area under the curve (AUC) of 0.944 (95%CI, 0.862-0.984), with internal validation confirming its consistency (AUC = 0.818, 95%CI, 0.597-0.948). Decision curve analysis (DCA) indicated clinical usefulness. Morphological features significantly contribute to risk stratification in sVAD patients. Our novel developed model, combining interdisciplinary parameters, is clinically useful for predicting IS risk. Further validation and in-depth research into the hemodynamics related to sVAD are necessary.

5.
Chem Commun (Camb) ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38982934

RESUMO

A ferrocene-modified COF, namely Ni-Tph-COF-Fc, was synthesized and applied in OER. Compared with Ni-Tph-COF-OH, Ni-Tph-COF-Fc shows improved performance with a current density of 99.6 mA cm-2, an overpotential of 450 mV, and a Tafel slope of 73.1 mV dec-1, which may be attributed to a synergy between introduced ferrocene and metalloporphyrin in the COFs. Moreover, the enhanced OER performance leads to an improved CO2RR performance with an FECO of 93.1%. This work represents an effective strategy to enhance the anodic OER performance and realize efficient CO2RR.

6.
J Cancer Res Clin Oncol ; 150(7): 335, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38969831

RESUMO

BACKGROUND: Ubiquilin-4 (UBQLN4), a member of the ubiquilin family, has received limited attention in cancer research to date. Here, we investigated for the first time the functional role and mechanism of UBQLN4 in non-small cell lung cancer (NSCLC). METHODS: The Cancer Genome Atlas (TCGA) database was employed to validate UBQLN4 as a differentially expressed gene. Expression differences of UBQLN4 in NSCLC cells and tissues were assessed using immunohistochemistry (IHC) experiment and western blotting (WB) experiment. Kaplan-Meier analysis was conducted to examine the association between UBQLN4 expression and NSCLC prognosis. Functional analyses of UBQLN4 were performed through cell counting kit-8 (CCK-8), colony formation, and transwell invasion assays. The impact of UBQLN4 on tumor-associated signaling pathways was assessed using the path scan intracellular signaling array. In vivo tumorigenesis experiments were conducted to further investigate the influence of UBQLN4 on tumor formation. RESULTS: UBQLN4 exhibited up-regulation in both NSCLC tissues and cells. Additionally, over-expression of UBQLN4 was associated with an unfavorable prognosis in NSCLC patients. Functional loss analyses demonstrated that inhibiting UBQLN4 could suppress the proliferation and invasion of NSCLC cells in both in vitro and in vivo settings. Conversely, functional gain experiments yielded opposite results. Path scan intracellular signaling array results suggested that the role of UBQLN4 is associated with the PI3K/AKT pathway, a correlation substantiated by in vitro and in vivo tumorigenesis experiments. CONCLUSION: We validated that UBQLN4 promotes proliferation and invasion of NSCLC cells by activating the PI3K/AKT pathway, thereby facilitating the progression of NSCLC. These findings underscore the potential of targeting UBQLN4 as a therapeutic strategy for NSCLC.


Assuntos
Proteínas Relacionadas à Autofagia , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Neoplasias Pulmonares , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Animais , Camundongos , Feminino , Masculino , Prognóstico , Linhagem Celular Tumoral , Camundongos Nus , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Transporte , Proteínas Nucleares
7.
J Agric Food Chem ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984620

RESUMO

Dietary fiber and polyphenols have been shown to possess antiobesity properties. However, their combined effects need further investigation. This study investigated the individual and combined effects of arabinoxylan oligosaccharides (AXOS) from rice bran and green tea polyphenols (GTP) in high-fat diet-induced obese mice. We found that the combination of AXOS and GTP (A + G) significantly reduced overall fat mass and improved lipid profiles, although the effects were not synergistic. AXOS and GTP regulated lipid metabolism in different tissues and exhibited counteractive effects on gut microbiota. AXOS decreased α diversity and promoted Bifidobacterium, with GTP counteracting these effects. In vitro fermentation confirmed that GTP counteracted AXOS-induced microbiota changes in a dose-dependent manner. This study highlights the potential of tailored combinations of dietary fiber and polyphenols to treat obesity while considering their complex microbial interplay.

9.
Skin Res Technol ; 30(7): e13848, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38978226

RESUMO

BACKGROUND: Plant polysaccharides have various biological activities. However, few studies have been conducted on the skin barrier of Prinsepia utilis Royle polysaccharide extract (PURP). MATERIALS AND METHODS: The proportions of polysaccharides, monosaccharides and proteins were determined by extracting polysaccharides from fruit meal using water. The healing rate was measured by cell scratch assays. SDS-damaged reconstructed human epidermal models, an acetone-ether-induced mouse model and an IL-4-induced cellular inflammation model were used to detect the effects of polysaccharides on the phenotype, HA, TEWL, and TEER, with further characterizations performed using QRT-PCR, Western blotting, immunofluorescence (IF) assays. RESULTS: PURP contained 35.73% polysaccharides and 11.1% proteins. PURP promoted cell migration and increased skin thickness in a reconstructed human epidermis model. The TEWL significantly decreased, and the HA content significantly increased. PURP significantly increased the TEER and decreased the permeability of the SDS-damaged reconstructed human epidermis model. Claudin-3, Claudin-4, and Claudin-5 were significantly upregulated. IF and Western blot analysis revealed that the Claudin-4 level significantly increased after treatment with PURP. Claudin-1, Claudin-3, Claudin-4, and Claudin-5 gene expression and IF and immunohistochemical staining were significantly increased in mice treated with acetone-ether. PURP promoted the expression of Claudin-1, Claudin-3, Claudin-4, and Claudin-5 after treatment with 100 ng/mL IL-4. PURP also downregulated the expression of NO, IL6, TNFα and NFκB in Raw 264.7 cells and in a mouse model. CONCLUSION: We hypothesize that PURP may repair the skin barrier by promoting the expression of the claudin family and can assist in skin therapy.


Assuntos
Claudinas , Extratos Vegetais , Polissacarídeos , Animais , Camundongos , Polissacarídeos/farmacologia , Humanos , Extratos Vegetais/farmacologia , Claudinas/metabolismo , Claudinas/genética , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Modelos Animais de Doenças , Movimento Celular/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo
10.
J Thorac Dis ; 16(6): 3828-3843, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38983152

RESUMO

Background: Ground-glass nodule (GGN) is the most common manifestation of lung adenocarcinoma on computed tomography (CT). Clinically, the success rate of preoperative diagnosis of GGN by puncture biopsy and other means is still low. The aim of this study is to investigate the clinical and radiomics characteristics of lung adenocarcinoma presenting as GGN on CT images using radiomics analysis methods, establish a radiomics model, and predict the classification of pathological tissue and instability of GGN type lung adenocarcinoma. Methods: This study retrospectively collected 249 patients with 298 GGN lesions who were pathologically confirmed of having lung adenocarcinoma. The images were imported into the Siemens scientific research prototype software to outline the region of interest and extract the radiomics features. Logistic model A (a radiomics model to identify the infiltration of lung adenocarcinoma manifesting as GGNs) was established using features after the dimensionality reduction process. The receiver operating characteristic (ROC) curve of the model on training set and the verification set was drawn, and the area under the curve (AUC) was calculated. Second, a total of 112 lesions were selected from 298 lesions originating from CT images of at least two occasions, and the time between the first CT and the preoperative CT was defined as not less than 90 days. The mass doubling time (MDT) of all lesions was calculated. According to the different MDT diagnostic thresholds instability was predicted. Finally, their AUCs were calculated and compared. Results: There were statistically significant differences in age and lesion location distribution between the "noninvasive" lesion group and the invasive lesion group (P<0.05), but there were no statistically significant differences in sex (P>0.05). Model A had an AUC of 0.89, sensitivity of 0.75, and specificity of 0.86 in the training set and an AUC of 0.87, sensitivity of 0.63, and specificity of 0.90 in the validation set. There was no significant difference statistically in MDT between "noninvasive" lesions and invasive lesions (P>0.05). The AUCs of radiomics models B1, B2 and B3 were 0.89, 0.80, and 0.81, respectively; the sensitivities were 0.71, 0.54, and 0.76, respectively; the specificities were 0.83, 0.77, and 0.60, respectively; and the accuracies were 0.78, 0.65, and 0.69, respectively. Conclusions: There were statistically significant differences in age and location of lesions between the "noninvasive" lesion group and the invasive lesion group. The radiomics model can predict the invasiveness of lung adenocarcinoma manifesting as GGNs. There was no significant difference in MDT between "noninvasive" lesions and invasive lesions. The radiomics model can predict the instability of lung adenocarcinoma manifesting as GGN. When the threshold of MDT was set at 813 days, the model had higher specificity, accuracy, and diagnostic efficiency.

11.
Res Sq ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38947048

RESUMO

Nutrient sensing and the subsequent metabolic responses are fundamental functions of animals, closely linked to diseases such as type 2 diabetes and various obesity-related morbidities. Among different metabolic regulatory signals, cytosolic Ca2+ plays pivotal roles in metabolic regulation, including glycolysis, gluconeogenesis, and lipolysis. Recently, intercellular calcium waves (ICWs), the propagation of Ca2+ signaling through tissues, have been found in different systems to coordinate multicellular responses. Nevertheless, our understanding of how ICWs are modulated and operate within living organisms remains limited. In this study, we explore the real-time dynamics, both in organ culture and free-behaving animals, of ICWs in Drosophila larval and adult adipose tissues. We identified Adipokinetic hormone (AKH), the fly functional homolog of mammalian glucagon, as the key factor driving Ca2+ activities in adipose tissue. Interestingly, we found that AKH, which is released in a pulsatile manner into the circulating hemolymph from the AKH-producing neurosecretory cells (APCs) in the brain, stimulates ICWs in the larval fat by a previously unrecognized gap-junction-independent mechanism to promote lipolysis. In the adult fat body, however, gap-junction-dependent random ICWs are triggered by a presumably uniformly diffused AKH. This highlights the stage-specific interplay of hormone secretion, extracellular diffusion, and intercellular communication in the regulation of Ca2+ dynamics. Additionally, we discovered that specific dietary amino acids activate the APCs, leading to increased intracellular Ca2+ and subsequent AKH secretion. Altogether, our findings identify that dietary amino acids regulate the release of AKH peptides from the APCs, which subsequently stimulates novel gap-junction-independent ICWs in adipose tissues, thereby enhancing lipid metabolism.

12.
Brain Struct Funct ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38914894

RESUMO

This study aims to reveal the association between sleep quality and crystallized intelligence (Gc), fluid intelligence (Gf), and the underlying brain structural basis. Using the data from the Human Connectome Project (N = 1087), we performed mediation analysis to explore whether regional brain structure related to sleep quality mediate the association between sleep quality and intellectual abilities, and further examined whether socioeconomic status (i.e., income and education level) moderate the mediation effect. Results showed that poorer sleep quality was associated with lower Gc rather than Gf, and worse sleep quality was associated with smaller volume and surface area in temporal lobe, including inferior temporal gyrus and middle temporal gyrus. Notably, temporal lobe structures mediated the association between sleep quality and Gc rather than Gf. Furthermore, socioeconomic status (i.e., income and education level) moderated the mediating effect, showing low socioeconomic status has a more significant mediating effect with stronger association between sleep quality and Gc as well as stronger association between temporal lobe structure and Gc in low socioeconomic status group. These findings suggest that individuals with higher socioeconomic status are less susceptible to the effect of sleep quality on Gc.

13.
J Mol Biol ; 436(16): 168650, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866091

RESUMO

Engineered reverse hairpin constructs containing a partial C-heptad repeat (CHR) sequence followed by a short loop and full-length N-heptad repeat (NHR) were previously shown to form trimers in solution and to be nanomolar inhibitors of HIV-1 Env mediated fusion. Their target is the in situ gp41 fusion intermediate, and they have similar potency to other previously reported NHR trimers. However, their design implies that the NHR is partially covered by CHR, which would be expected to limit potency. An exposed hydrophobic pocket in the folded structure may be sufficient to confer the observed potency, or they may exist in a partially unfolded state exposing full length NHR. Here we examined their structure by crystallography, CD and fluorescence, establishing that the proteins are folded hairpins both in crystal form and in solution. We examined unfolding in the milieu of the fusion reaction by conducting experiments in the presence of a membrane mimetic solvent and by engineering a disulfide bond into the structure to prevent partial unfolding. We further examined the role of the hydrophobic pocket, using a hairpin-small molecule adduct that occluded the pocket, as confirmed by X-ray footprinting. The results demonstrated that the NHR region nominally covered by CHR in the engineered constructs and the hydrophobic pocket region that is exposed by design were both essential for nanomolar potency and that interaction with membrane is likely to play a role in promoting the required inhibitor structure. The design concepts can be applied to other Class 1 viral fusion proteins.

14.
J Cancer ; 15(12): 3930-3938, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911366

RESUMO

Background: To better assess the peripheral immune status and aid in the early diagnosis and prognosis of tumors, we compared the proportion and absolute counting of peripheral immune cell subsets in healthy individuals and tumor patients of varying ages, taking into account the impact of sex and tumor metastasis. Methods: We used peripheral blood mononuclear cell (PBMC) samples from 520 patients with various tumor types and 109 healthy volunteers. The absolute numbers of lymphocytes and monocytes were identified by an automated blood analyzer, and multi-parameter flow cytometry was used to examine the subsets of natural killer (NK) cells (CD3-CD16+CD56+), T cells (CD3+CD4+/CD8+), and mononuclear cells (CD14+) in PBMC. Results: The percentage of T cells (CD3+) in peripheral blood mononuclear cells (PBMC) was 55.83% VS 45.54% (P<0.0001) between healthy volunteers and tumor patients, showing a significant downward trend. Meanwhile, the percentages of monocytes (CD14+) and NK cells (CD3-CD16+CD56+) showed a significant upward trend. Single factor or multifactor analysis yielded identical findings on the proportion of PBMC between healthy individuals and patients with different malignancies, considering the three confounding variables of age, sex, and tumor metastasis. Conclusion: The proportion and absolute counting of acquired immune T cells, innate immune NK cells, and monocytes in PBMCs all exhibit substantial changes between cancer patients and healthy individuals, and the differences are influenced by age, sex, and tumor progression.

15.
Curr Neurovasc Res ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38918991

RESUMO

BACKGROUND: Neutrophil-To-Albumin Ratio (NAR) is a novel inflammatory biomarker. However, the potential prognostic value of NAR in acute ischemic stroke (AIS) remains unclear. This study aimed to evaluate whether NAR levels correlated with the 3-month modified Rankin scale (mRS) in patients with AIS. METHODS: AIS patients were included in this retrospective study. NAR was calculated as the ratio of absolute neutrophil count to serum albumin level. Logistic regression analyses were used to investigate the effect of NAR on 3-month mRS of AIS. The predictive values of NAR, albumin level, and neutrophil count were compared utilizing receiver operating characteristic (ROC) curves. Moreover, subgroup analyses and interaction tests were conducted to evaluate the consistency of NAR's effect on AIS prognosis. RESULTS: Of the 780 patients included, 403 (51.67%) had a poor clinical outcome (mRS 3-6) at 3 months. NAR was independently correlated to 3-month poor functional outcome after adjusting for confounders (Odds ratios (OR), 9.34; 95% confidence intervals (CI), 1.09 to 80.13; p =0.0417). Subgroup analysis showed a relative effect consistent with the overall population results, and no statistical interactions were found in the subgroups (all p for interaction > 0.05). The ROC curve showed that the prognosis-related cutoff value for NAR was 0.123, with corresponding specificity and sensitivity of 53.55% and 63.94%, respectively. When comparing the predictive power, NAR (0.590; 95%CI 0.549-0.630) exhibited the highest area under the curve (AUC) of ROC compared to neutrophils (0.584; 95%CI 0.543-0.624) and albumin (0.540; 95%CI 0.500-0.581). CONCLUSION: There is a positive relationship between NAR levels and 3-month poor functional outcomes in AIS patients, supporting the potential of NAR as a readily available and economic serum biomarker for the early identification of AIS prognosis. Further studies are required to validate the prognostic value and clinical utility of the NAR.

16.
Mol Neurobiol ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922485

RESUMO

Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models. Male Sprague-Dawley rats and male rhesus monkeys were subjected to classical MA self-administration training, and fecal samples were collected before and after MA self-administration training, respectively. 16S rRNA sequencing was used for GM analyses. We found that GM changes were more pronounced in rats than in rhesus monkeys, as evidenced by more GM taxa producing significant differences before and after MA self-administration training in rats than in monkeys. We also found that the expression of the genus Clostridia_vadinBB60_group significantly decreased after MA self-administration training in both rats and rhesus monkeys. Lactobacillus changes were significantly negatively correlated with total MA uptake in rats (Pearson R = - 0.666, p = 0.035; Spearman R = - 0.721, p = 0.023), whereas its change was also highly negatively correlated with total MA uptake in rhesus monkeys (Pearson R = - 0.882, p = 0.118; Spearman R = - 1.000, p = 0.083), although this was not significant. These findings suggest that MA causes significant alterations in GM in both rhesus monkeys and rats and that the genus Lactobacillus might be a common therapeutic target for MA uptake prevention across the species.

17.
Curr Med Sci ; 44(3): 545-553, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38900386

RESUMO

OBJECTIVE: Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer. However, the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer (CRC) cells is unclear. This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells. METHODS: The expression of TOPK was detected in CRC tissues by immunohistochemistry, and the effect of TOPK knockdown was detected in CRC cells by Western blotting. CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells. Furthermore, proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy. DNA damage was detected by the comet assay. Changes in the DNA damage response signaling pathway were analyzed by Western blotting, and apoptosis was detected by flow cytometry. RESULTS: The expression of TOPK was significantly greater in CRC tissues at grades 2-4 than in those at grade 1. After irradiation, CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins, including phospho-cyclin-dependent kinase 1 (p-CDK1), phospho-ataxia telangiectasia-mutated (p-ATM), poly ADP-ribose polymerase (PARP), and meiotic recombination 11 homolog 1 (MRE11). CONCLUSIONS: TOPK was overexpressed in patients with moderately to poorly differentiated CRC. Moreover, TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.


Assuntos
Apoptose , Neoplasias Colorretais , Dano ao DNA , Tolerância a Radiação , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/patologia , Dano ao DNA/efeitos da radiação , Tolerância a Radiação/genética , Tolerância a Radiação/efeitos dos fármacos , Linhagem Celular Tumoral , Masculino , Técnicas de Silenciamento de Genes , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Transdução de Sinais , Feminino , Fosforilação , Quinases de Proteína Quinase Ativadas por Mitógeno
18.
Clin Lab ; 70(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38868871

RESUMO

BACKGROUND: Heterophilic antibodies (HA) are one of the main substances that interfere with immunology, especially chemiluminescence immunoassay. Non-specific binding, labeling antibodies, bridging to capture antibodies, or labeling antigens can interfere with the detection process, leading to serious discrepancies between the measured results and clinical manifestations, and even delaying clinical diagnosis and treatment. METHODS: This paper is a case of epidemic hemorrhagic fever causing pseudo CEA elevation caused by heterophagy induced antibodies in the body. RESULTS: The patient's CEA detected on the ABBOTT detection platform was 51.1 ng/mL, and on the ROCHE detection platforms it was 4.66 ng/mL, and treated by PEG precipitation it was 45.2 ng/mL, after diluting the sample the CEA was 50.2 ng/mL, meanwhile the patient's platelets were 96 x 109/L and serum creatinine was 188.4 µmol/L, epidemic hemorrhagic fever IgM antibody was positive. CONCLUSIONS: When the test results do not match clinical symptoms, further confirmation is required through additional testing. Patients who use mouse monoclonal antibody preparations for diagnosis or treatment may have human anti-mouse antibodies in their serum, and the test results may falsely increase or decrease.


Assuntos
Antígeno Carcinoembrionário , Humanos , Anticorpos Heterófilos/sangue , Anticorpos Heterófilos/imunologia , Antígeno Carcinoembrionário/sangue , Imunoglobulina M/sangue , Feminino , Idoso
19.
20.
World J Gastroenterol ; 30(21): 2763-2776, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38899335

RESUMO

BACKGROUND: At present, liver transplantation (LT) is one of the best treatments for hepatocellular carcinoma (HCC). Accurately predicting the survival status after LT can significantly improve the survival rate after LT, and ensure the best way to make rational use of liver organs. AIM: To develop a model for predicting prognosis after LT in patients with HCC. METHODS: Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated. The expression levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, Golgi protein 73, cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer. The best cutoff value of biomarkers was determined using the Youden index. Cox regression analysis was used to identify the independent risk factors. A forest model was constructed using the random forest method. We evaluated the accuracy of the nomogram using the area under the curve, using the calibration curve to assess consistency. A decision curve analysis (DCA) was used to evaluate the clinical utility of the nomograms. RESULTS: The total tumor diameter (TTD), vascular invasion (VI), AFP, and cytokeratin-18 epitopes M30 (CK18-M30) were identified as important risk factors for outcome after LT. The nomogram had a higher predictive accuracy than the Milan, University of California, San Francisco, and Hangzhou criteria. The calibration curve analyses indicated a good fit. The survival and recurrence-free survival (RFS) of high-risk groups were significantly lower than those of low- and middle-risk groups (P < 0.001). The DCA shows that the model has better clinical practicability. CONCLUSION: The study developed a predictive nomogram based on TTD, VI, AFP, and CK18-M30 that could accurately predict overall survival and RFS after LT. It can screen for patients with better postoperative prognosis, and improve long-term survival for LT patients.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Nomogramas , alfa-Fetoproteínas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/sangue , Masculino , Transplante de Fígado/efeitos adversos , Pessoa de Meia-Idade , Feminino , Fatores de Risco , alfa-Fetoproteínas/análise , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Prognóstico , Adulto , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Queratina-18/sangue , Queratina-18/análise , Técnicas de Apoio para a Decisão
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