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1.
BMC Gastroenterol ; 24(1): 183, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38783185

RESUMO

OBJECTIVE: To evaluate the diagnostic accuracy of aspartate aminotransferase(AST)/ alanine transaminase (ALT), AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4) and gamma-glutamyl transpeptidase to platelet count ratio (GPR) for hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS: A total of 1210 CHB patients who underwent liver biopsy were divided into two groups: patients with no significant fibrosis (control group) and patients with significant fibrosis, and routine laboratory tests were retrospectively included. Logistic regression models were used for the prediction, and the area under the receiver operating characteristic (AUROC) was used to assess the diagnostic accuracy. RESULTS: A total of 631 (52.1%) and 275 (22.7%) patients had significant fibrosis (≥ S2) and advanced fibrosis (≥ S3), respectively. The GPR showed significantly higher diagnostic accuracy than that of APRI, FiB-4, and AST/ALT to predict ≥ S2(significant fibrosis) and ≥ S3 fibrosis(advanced fibrosis), with an AUROC was 0.69 (95%CI: 0.66-0.71) and 0.72 (0.69-0.75), respectively. After stratified by the status of HBeAg ( positive or negative), GPR, APRI, and FiB-4 showed improved predicting performance for significant fibrosis and advanced fibrosis in HBeAg positive patients, with the most significant improvement was shown for GPR in predicting significant fibrosis (AUROC = 0.74, 95%CI: 0.70-0.78). CONCLUSIONS: Among the four noninvasive models, GPR has the best performance in the diagnosis of hepatic fibrosis in CHB patients and is more valuable in HBeAg-positive patients.


Assuntos
Alanina Transaminase , Aspartato Aminotransferases , Hepatite B Crônica , Cirrose Hepática , gama-Glutamiltransferase , Humanos , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Hepatite B Crônica/sangue , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Cirrose Hepática/diagnóstico , Masculino , Feminino , Contagem de Plaquetas , Aspartato Aminotransferases/sangue , Adulto , Alanina Transaminase/sangue , Estudos Retrospectivos , gama-Glutamiltransferase/sangue , Pessoa de Meia-Idade , Curva ROC , Biópsia , Fígado/patologia , Antígenos E da Hepatite B/sangue , Biomarcadores/sangue , Modelos Logísticos , Valor Preditivo dos Testes , Índice de Gravidade de Doença
2.
Biol Reprod ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38785325

RESUMO

Klinefelter syndrome (KS) is the most prevalent chromosomal disorder occurring in males. It is defined by an additional X chromosome, 47,XXY, resulting from errors in chromosomal segregation during parental gametogenesis. A major phenotype is impaired reproductive function, in the form of low testosterone and infertility. This review comprehensively examines the genetic and physiological factors contributing to infertility in KS, in addition to emergent assisted reproductive technologies, and the unique ethical challenges KS patients face when seeking infertility treatment. The pathology underlying KS is increased susceptibility for meiotic errors during spermatogenesis, resulting in aneuploid or even polyploid gametes. Specific genetic elements potentiating this susceptibility include polymorphisms in checkpoint genes regulating chromosomal synapsis and segregation. Physiologically, the additional sex chromosome also alters testicular endocrinology and metabolism by dysregulating interstitial and Sertoli cell function, collectively impairing normal sperm development. Additionally, epigenetic modifications like aberrant DNA methylation are being increasingly implicated in these disruptions. We also discuss assisted reproductive approaches leveraged in infertility management for KS patients. Application of assisted reproductive approaches, along with deep comprehension of the meiotic and endocrine disturbances precipitated by supernumerary X chromosomes, shows promise in enabling biological parenthood for KS individuals. This will require continued multidisciplinary collaboration between experts with background of genetics, physiology, ethics and clinical reproductive medicine.

3.
Discov Oncol ; 15(1): 178, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771435

RESUMO

OBJECTIVE: Melanoma, with its high degree of malignancy, stands as one of the most dangerous skin cancers and remains the primary cause of death from skin cancer. With studies demonstrating the potential of traditional Chinese medicine to intervene and treat melanoma, we turned our attention to celastrol. Celastrol is a triterpene compound extracted from the traditional Chinese medicine derived from Tripterygium wilfordii. Previous studies have shown that celastrol exerts inhibitory effects on various malignant tumors, including melanoma. Hence, our goal was to clarify the impact of celastrol on cell viability, apoptosis, and cell cycle progression by elucidating its effects on the PI3K/AKT/mTOR pathway. METHODS: CCK-8 and wound healing assays were used to determine the effect of celastrol on the viability and migration of B16-F10 cells. Changes in cell apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were detected by flow cytometry. PI3K/AKT/mTOR pathway proteins and HIF-α mRNA expression in B16-F10 cells were detected by western blotting and qPCR. Moreover, the addition of a PI3K activator demonstrated that celastrol could inhibit the function of B16-F10 cells via the PI3K/AKT/mTOR pathway. RESULTS: Celastrol inhibited the viability and migration of B16-F10 cells. Through the inhibition of the PI3K/AKT/mTOR pathway down-regulates the expression of HIF-α mRNA, thereby causing an increase of ROS in cells and a decrease in the mitochondrial membrane potential to promote cell apoptosis and cell cycle arrest. The inhibitory effect of celastrol on B16-F10 cells was further demonstrated by co-culturing with a PI3K activator. CONCLUSION: Celastrol inhibits the function of B16-F10 cells by inhibiting the PI3K/AKT/mTOR cellular pathway and regulating the expression of downstream HIF-α mRNA.

4.
Aesthet Surg J ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567442

RESUMO

BACKGROUND: Macrophage-mediated inflammatory response in the early post-grafting period restricts fat graft retention. Pyroptosis is a novel type of programmed cell death that extensively participates in inflammatory pathologies. OBJECTIVES: This study sought to determine whether macrophage pyroptosis is activated during the inflammatory phase after fat grafting and to investigate the efficacy of a pyroptosis inhibitor, disulfiram (DSF) in fat graft retention. METHODS: We established a C57BL/6 mice fat grafting model and then analyzed macrophage pyroptosis. DSF (50 mg/kg, every other day) was intraperitoneally injected started from 1 h prior to fat grafting and continued for 14 days. An in vitro co-culture system was established in which mouse RAW264.7 macrophages were co-cultured with apoptotic adipocytes to further validate the findings of the in vivo studies and to explore the underlying mechanisms. RESULTS: Here we reported that macrophage pyroptosis was activated in both fat grafts and in vitro co-culture models. DSF was found to be a potent pyroptosis inhibitor to promote M2 macrophage polarization. In addition, DSF was demonstrated to enhance vascularization and graft retention. CONCLUSIONS: Our results suggested that pyroptosis plays a crucial role in the inflammatory cascade within fat grafts. DSF, being a clinically available drug could be translated into a clinically effective drug for improving fat graft survival via inhibiting macrophage pyroptosis, thereby inducing M2 macrophage polarization and promoting neovascularization.

5.
Obes Surg ; 34(5): 1793-1800, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38587781

RESUMO

BACKGROUND: Patients with obesity are more sensitive to pain and more likely to have acute postoperative pain (APP). Studies have shown that the depth of anesthesia may affect the incidence of APP. The purpose of the study was to look into the connection between APP and depth of anesthesia in patients with obesity undergoing laparoscopic sleeve gastrectomy. METHODS: This is a prospective, double-blinded randomized clinical trial, 90 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into two groups: the light anesthesia group (Bispectral Index of 50, BIS 50) and the deep anesthesia group (BIS 35). The degree of pain was evaluated by the visual analogue scale (VAS) at 0, 12, 24, 48, and 72 h after surgery. The use of analgesics, grade of postoperative nausea and vomiting (PONV), and the Quality of Recovery-15 (QoR-15) score were recorded. RESULTS: The VAS scores at rest or coughing at 0, 12, and 24 h after surgery in the BIS 35 group were lower than those in the BIS 50 group (P < 0.05). Fewer patients in the deep anesthesia group needed analgesia during the recovery period, and patient satisfaction was higher on the 3rd day after surgery (P < 0.015, P < 0.032, respectively). CONCLUSIONS: For patients with obesity, maintaining a deeper depth of anesthesia during surgery is beneficial to reduce APP causes less need for additional analgesic drugs, and improves patient satisfaction.


Assuntos
Anestesia , Laparoscopia , Obesidade Mórbida , Humanos , Laparoscopia/efeitos adversos , Estudos Prospectivos , Obesidade Mórbida/cirurgia , Anestesia/efeitos adversos , Analgésicos/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/epidemiologia , Obesidade/cirurgia , Gastrectomia/efeitos adversos
6.
Medicine (Baltimore) ; 103(16): e37846, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640324

RESUMO

The current study aimed to investigate the potential role of astragaloside IV (AS-IV) in improving cellular lipid deposition and its underlying mechanism. A fatty liver cell model was established by treating hepatoma cells with palmitic acid. AS-IV and SC79 were used for treatment. Oil Red O staining was applied to detect intracellular lipid deposition, and transmission electron microscopy was utilized to assess autophagosome formation. Immunofluorescence double staining was applied to determine microtubule-associated proteins 1A/1B light chain 3 (LC3) expression. Western blot analysis was performed to detect the expression of LC3, prostacyclin, Beclin-1, V-akt murine thymoma viral oncogene homolog (Akt), phosphorylated Akt, mTOR, and phosphorylated mTOR. Oil Red O staining revealed that AS-IV reduced intracellular lipid accumulation. Further, it increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in the cells. It also reduced the phosphorylation levels of Akt and mTOR and the levels of prostacyclin. However, the effects of AS-IV decreased with SC79 treatment. In addition, LC3B + BODIPY493/503 fluorescence double staining showed that AS-IV reduced intracellular lipid deposition levels by enhancing autophagy. AS-IV can reduce lipid aggregation in fatty liver cells, which can be related to enhanced hepatocyte autophagy by inhibiting the Akt/mTOR signaling pathway.


Assuntos
Autofagia , Fígado Gorduroso , Metabolismo dos Lipídeos , Saponinas , Triterpenos , Animais , Humanos , Camundongos , Autofagia/efeitos dos fármacos , Compostos Azo , Proteína Beclina-1/metabolismo , Fígado Gorduroso/tratamento farmacológico , Lipídeos , Prostaglandinas I , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/farmacologia , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Triterpenos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos
7.
ACS Omega ; 9(11): 13067-13080, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38524427

RESUMO

In the realm of postcombustion carbon capture, diethylenetriamine (DETA), recognized for its substantial CO2 absorption capacity, presents a formidable challenge due to its corrosive impact on equipment. This study delves into the corrosion behavior of 20# carbon steel immersed in DETA solutions under varying conditions, employing weight loss and electrochemical methods. The investigation incorporates scanning electron microscopy/energy-dispersive spectroscopy and X-ray diffraction analyses for characterization. Corrosion experiments were also conducted in monoethanolamine (MEA) solutions for a comparative analysis. Results from the corrosion tests in DETA solutions mirror the temperature-dependent corrosion rate (CR) observed in MEA. However, a distinctive trend emerges as the CO2 loading of DETA increases from 0.2 mol CO2/mol amine to 1.2 mol CO2/mol amine, leading to a continuous decrease in the CR of carbon steel-contrary to MEA solutions. This anomaly is attributed to DETA's robust complexing ability with metal ions and its elevated solubility of Fe2+ in solution. Additionally, an examination of the corrosion mechanism in the presence of oxygen was conducted through characterizing the specimen surface and solution precipitates postexperiment. The absence of a protective FeCO3 layer can be attributed to insufficient concentrations of free Fe2+ and CO32- in the solution, failing to achieve the minimum saturation required for protective film formation. The insights gained from studying the corrosion behavior of carbon steel in DETA solutions lay the groundwork for subsequent developments in corrosion inhibitors.

8.
PLoS One ; 19(3): e0300723, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547077

RESUMO

Preclinical models of cancer are vital for assessing and predicting efficacies and toxicities of novel treatments prior to testing in human subjects. Current pancreatic tumor models exhibit variable growth rates, unpredictable tumor size after implantation in non-native tissues, or require surgical implantation. Surgical implantation in the pancreas may produce not only unpredictable tumor uptake but could also elicit additional inflammatory responses. In searching for a pancreatic carcinoma cell that can be introduced into a mouse via simple injection, we found that Pan02, a murine ductal pancreatic adenocarcinoma derived from a pancreatic lesion of a C57BL/6 mouse, inoculated peritoneally can consistently produce pancreatic tumors. This intraperitoneal, but not intravenous, introduction of Pan02 cells leads to the attachment and growth of Pan02 in the pancreas before spreading to other tissues. Time-course tissue analysis indicates that the Pan02 cells first find, infiltrate, and grow within the pancreas, producing a pancreatic tumor model. This model appears to mimic pancreatic cancer development in humans and is the first reported use of Pan02 cells to produce orthotopic pancreatic and metastatic neoplasms in a mouse model without the need for tumor implantation within matrices or survival surgeries. This orthotopic pancreatic tumor model, with consistent tumor uptake, synchronized tumor development and survival, and predictable outcomes may enable and accelerate the preclinical evaluation of treatment candidates for pancreatic cancer.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Neoplasias Pancreáticas/patologia , Adenocarcinoma/patologia , Camundongos Endogâmicos C57BL , Carcinoma Ductal Pancreático/patologia , Pâncreas/patologia , Modelos Animais de Doenças , Linhagem Celular Tumoral
9.
Chembiochem ; 25(10): e202400087, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38439618

RESUMO

The development of genetic reporters for magnetic resonance imaging (MRI) is essential for investigating biological functions in vivo. However, current MRI reporters have low sensitivity, making it challenging to create significant contrast against the tissue background, especially when only a small fraction of cells express the reporter. To overcome this limitation, we developed an approach for amplifying the sensitivity of molecular MRI by combining a chemogenetic contrast mechanism with a biophysical approach to increase water diffusion through the co-expression of a dual-gene construct comprising an organic anion transporting polypeptide, Oatp1b3, and a water channel, Aqp1. We first show that the expression of Aqp1 amplifies MRI contrast in cultured cells engineered to express Oatp1b3. We demonstrate that the contrast amplification is caused by Aqp1-driven increase in water exchange, which provides the gadolinium ions internalized by Oatp1b3-expressing cells with access to a larger water pool compared with exchange-limited conditions. We further show that our methodology allows cells to be detected using approximately 10-fold lower concentrations of gadolinium than that in the Aqp1-free scenario. Finally, we show that our approach enables the imaging of mixed-cell cultures containing a low fraction of Oatp1b3-labeled cells that are undetectable on the basis of Oatp1b3 expression alone.


Assuntos
Aquaporina 1 , Genes Reporter , Imageamento por Ressonância Magnética , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto , Água , Água/química , Humanos , Imageamento por Ressonância Magnética/métodos , Aquaporina 1/metabolismo , Aquaporina 1/genética , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/metabolismo , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Gadolínio/química , Meios de Contraste/química , Meios de Contraste/metabolismo , Células HEK293 , Animais
10.
J Hepatol ; 80(1): 41-52, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37858684

RESUMO

BACKGROUND & AIMS: HBsAg loss is only observed in a small proportion of patients with chronic hepatitis B (CHB) who undergo interferon treatment. Investigating the host factors crucial for functional cure of CHB can aid in identifying individuals who would benefit from peginterferon-α (Peg-IFNα) therapy. METHODS: We conducted a genome-wide association study (GWAS) by enrolling 48 patients with CHB who achieved HBsAg loss after Peg-IFNα treatment and 47 patients who didn't. In the validation stage, we included 224 patients, of whom 90 had achieved HBsAg loss, to validate the identified significant single nucleotide polymorphisms. To verify the functional involvement of the candidate genes identified, we performed a series of in vitro and in vivo experiments. RESULTS: GWAS results indicated a significant association between the rs7519753 C allele and serum HBsAg loss in patients with CHB after Peg-IFNα treatment (p = 4.85 × 10-8, odds ratio = 14.47). This association was also observed in two independent validation cohorts. Expression quantitative trait locus analysis revealed higher hepatic TP53BP2 expression in individuals carrying the rs7519753 C allele (p = 2.90 × 10-6). RNA-sequencing of liver biopsies from patients with CHB after Peg-IFNα treatment revealed that hepatic TP53BP2 levels were significantly higher in the HBsAg loss group compared to the HBsAg persistence group (p = 0.035). In vitro and in vivo experiments demonstrated that loss of TP53BP2 decreased interferon-stimulated gene levels and the anti-HBV effect of IFN-α. Mechanistically, TP53BP2 was found to downregulate SOCS2, thereby facilitating JAK/STAT signaling. CONCLUSION: The rs7519753 C allele is associated with elevated hepatic TP53BP2 expression and an increased probability of serum HBsAg loss post-Peg-IFNα treatment in patients with CHB. TP53BP2 enhances the response of the hepatocyte to IFN-α by suppressing SOCS2 expression. IMPACT AND IMPLICATIONS: Chronic hepatitis B (CHB) remains a global public health issue. Although current antiviral therapies are more effective in halting disease progression, only a few patients achieve functional cure for hepatitis B with HBsAg loss, highlighting the urgent need for a cure for CHB. This study revealed that the rs7519753 C allele, which is associated with high expression of hepatic TP53BP2, significantly increases the likelihood of serum HBsAg loss in patients with CHB undergoing Peg-IFNα treatment. This finding not only provides a promising predictor for HBsAg loss but identifies a potential therapeutic target for Peg-IFNα treatment. We believe our results are of great interest to a wide range of stakeholders based on their potential clinical implications.


Assuntos
Antivirais , Hepatite B Crônica , Humanos , Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/genética , Estudo de Associação Genômica Ampla , Quimioterapia Combinada , Interferon-alfa/farmacologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Antígenos E da Hepatite B , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , DNA Viral/genética , Proteínas Reguladoras de Apoptose
11.
Hum Cell ; 37(1): 285-296, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37801261

RESUMO

There is a cross-link between the placenta and cancer development, as the placenta is grown as a highly invasive tumour-like organ. However, placental development is strictly controlled. Although the underlying mechanism of this control is largely unknown, it is now well-recognised that extracellular vesicles (EVs) released from the placenta play an important role in controlling placenta proliferation and invasion, as placental EVs have shown their effect on regulating maternal adaptation. Better understanding the tumour-like mechanism of the placenta could help to develop a therapeutic potential in cancers. In this study, by RNA sequencing of placental EVs, 20 highly expressed microRNAs (miRNAs) in placental EVs were selected and analysed for their functions on ovarian and endometrial cancer. There were up to seven enriched miRNAs, including miRNA-199a-3p, miRNA-143-3p, and miRNA-519a-5p in placental EVs showing effects on the inhibition of ovarian and endometrial cancer cell proliferation and migration, and promotion of cancer cell death, reported in the literature. Most of these miRNAs have been reported to be downregulated in ovarian and endometrial cancer. Transfection of ovarian and endometrial cancer cells with mimics of miRNA-199a-3p, miRNA-143-3p, and miRNA-519a-5p significantly reduced the cell viability. Our findings could provide strategies for using these naturally occurring miRNAs to develop a novel method to treat ovarian and endometrial cancer in the future.


Assuntos
Neoplasias do Endométrio , Vesículas Extracelulares , MicroRNAs , Humanos , Gravidez , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Placenta , Endométrio/metabolismo , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/metabolismo , Vesículas Extracelulares/metabolismo
12.
Quant Imaging Med Surg ; 13(12): 8218-8229, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38106238

RESUMO

Background: Pericoronary artery coronary tissue (PACT) is a type of epicardial fat that can reflect the state of the coronary artery (inflammation, etc.). However, it cannot be reasonably and efficiently utilized in routine computed tomography (CT) examination. The aim of this study was to use artificial intelligence (AI) software to analyze coronary computed tomography angiography (CCTA) and measure the coronary perivascular fat attenuation index (FAI) of patients. The relationship between FAI and the occurrence of coronary adverse events and the degree of coronary stenosis were further analyzed. Methods: This study involved patients who experienced CCTA in West China Hospital, Sichuan University, from January 2012 to December 2012. These patients were followed up to 2020 and classified according to the occurrence of coronary adverse events and the degree of stenosis of the lumen. For all patients, AI software was used to analyze the CCTA images of patients, and the FAI of 3 coronary arteries, the left anterior descending artery (LAD), the left circumflex artery (LCX), and the right coronary artery (RCA), was measured. Moreover, the relationship between FAI and patients with different degrees of coronary stenosis and adverse coronary events was determined. Results: Comparisons between any 2 groups showed that the differences in the FAI among the 4 groups for the LAD were significant (all P values <0.05). There were no significant differences between the group with less-than-moderate stenosis (Mb) without adverse events and the group with moderate-or-above stenosis (M) with no adverse events for the LCX (P>0.05). For the remaining groups, FAI values exhibited statistically significant differences (P<0.05). According to the degree of lumen stenosis, the patients were divided into groups according to LAD, LCX, and RCA and the sum of the 3 vessels. There were significant differences in coronary FAI among the groups with different degrees of lumen stenosis for the sum of the 3 vessels, the LAD, and the LCX (P<0.05). Conclusions: FAI can reflect the state of the coronary artery, which is related to inflammation of the coronary lumen. Moreover, there is a relationship between FAI and the degree of stenosis in the coronary lumen: the narrower the coronary lumen is, the higher the FAI around the lumen.

13.
Cell Death Discov ; 9(1): 344, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37717021

RESUMO

Wilson's disease (WD) is an inherited disease characterized by copper metabolism disorder caused by mutations in the adenosine triphosphatase copper transporting ß gene (ATP7B). Currently, WD cell and animal model targeting the most common R778L mutation in Asia is lacking. In addition, the mechanisms by which hepatocytes resist copper toxicity remain to be further elucidated. In this study, we aimed to construct a novel WD cell model with R778L mutation and dissected the molecular basics of copper resistance. A novel HepG2 cell line stably expressing the ATP7B R778L gene (R778L cell) was constructed. The expression of necroptosis- and autophagy-related molecules was detected by PCR and Western blot (WB) in wild-type (WT) HepG2 and R778L cells with or without CuSO4 treatment. In addition, we detected and compared the levels of autophagy and necroptosis in CuSO4-treated R778L cells with the activation and inhibition of autophagy. Moreover, the mRNA and protein levels of autophagy and necroptosis signaling molecules were compared in R778L cells with the overexpression and knockdown of Unc-51 Like Autophagy Activating Kinase 1 (ULK1) and Autophagy Related 16 Like 1 (ATG16L1). We successfully constructed an R778L mutation HepG2 cell line. CuSO4 triggered the enhanced expression of autophagy and necroptosis signaling molecules in WT HepG2 cells and R778L cells. Remarkably, higher levels of autophagy and necroptosis were observed in R778L cells compared with those in WT cells. Autophagy activation led to weakened necroptosis mediated by RIPK3 and MLKL, conversely, autophagy inhibition brought about enhanced necroptosis. At the molecular level, ULK1- and ATG16L1 overexpression resulted in reduced necroptosis levels and vice versa. ULK1- and ATG16L1-mediated autophagy activation protects hepatocytes against RIPK3- and MLKL-mediated necroptosis in our new WD cell model treated with CuSO4. Targeted therapy by autophagy activation or necroptosis inhibition may be a novel and effective strategy to treat WD.

14.
Sci Total Environ ; 904: 166883, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37690764

RESUMO

Mature landfill leachate is a refractory organic wastewater, and needs physical and chemical pretreatments contemporaneously, e.g. iron-carbon micro-electrolysis (IC-ME). In this study, a novel iron-carbon (Fe-C) material was synthesized from waste activated sludge to be utilized in IC-ME for landfill leachate treatment. The pyrolysis temperature, mass ratio of iron to carbon, and solid-liquid ratio in leachate treatment were optimized as 900 °C with 1.59 and 34.7 g/L. Under these optimal conditions, the chemical oxygen demand (COD) removal efficiency reached 79.44 %, which was 2.6 times higher than that of commercial Fe-C material (30.1%). This excellent COD removal performance was indicated to a better mesoporous structure, and uniform distribution of zero-valent iron in novel Fe-C material derived from sludge. The contribution order of COD removal in IC-ME treatment for landfill leachate was proven as coagulation, adsorption, and redox effects by a contrast experiment. The removal of COD includes synthetic organic compounds, e.g. carcinogens, pharmaceuticals and personal care products. The contents of CHO, CHON, and CHOS compounds of dissolved organic matter (DOM) in the leachate were decreased, and both the molecular weight and unsaturation of lipids, lignin, and tannic acids concentration were also reduced. Some newly generated small molecular DOM in the treated leachate further confirmed the existence of the redox effect to degrade DOM in leachate. The total cost of sludge-derived Fe-C material was only USD$ 152.8/t, which could save 76% of total compared with that of commercial Fe-C materials. This study expands the prominent source of Fe-C materials with excellent performance, and deepens the understanding of its application for leachate treatment.

15.
Environ Pollut ; 336: 122406, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37597731

RESUMO

Studies have shown that exposure to either microplastics (MPs) or di-(2-ethylhexyl) phthalic acid (DEHP) alone can cause neurotoxicity in animals, but it remains uncertain whether and to what extent co-exposure to these two substances, which often occur together in reality, can also induce neurotoxicity. This study aimed to investigate the neurotoxicity and molecular mechanisms of combined exposure to DEHP and polypropylene microplastics (synthetic PP-MPs were used), the microplastics most commonly encountered by young children, in immature mice. The results showed that exposure to PP-MPs and/or DEHP did cause neurotoxic effects in immature mice, including induction of neurocognitive and memory deficits, damage to the CA3 region of the hippocampus, increased oxidative stress, and decreased AChE activity in the brain. The severity of the neurotoxicity increased with increasing concentrations of PP-MPs, combined exposure to PP-MPs and DEHP exhibited additive or synergistic effects. Transcriptomic analyses revealed that the PP-MPs and/or DEHP exposure altered the expression profiles of gene clusters involved in the stress response, and in protein processing in endoplasmic reticulum. Quantitative analyses further indicated that PP-MPs and/or DEHP exposure inhibited the activity of the heat shock response mediated by heat shock transcription factor 1, while chronically activated the unfolded protein response, consequently inducing neurotoxicity through neuronal apoptosis and neuroinflammation in the immature mice. As a pioneer study to highlight the neurotoxicity induced by combined exposure to PP-MPs and DEHP in immature mice, this research provides new insights into mitigating the health risks of PP-MPs and DEHP exposure in young children.

16.
Biosci Rep ; 43(8)2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37503762

RESUMO

The biological links between cancer and pregnancy are of interest due to parallel proliferative, immunosuppressive, and invasive mechanisms between tumour and placental cells. However, the proliferation and invasion of placental cells are strictly regulated. The understanding of this regulation is largely unknown. Placental extracellular vesicles (EVs) may play an important role in this regulation, as placental EVs are known to contribute to maternal adaptation, including adaptation of the vascular and immune systems. We have previously reported that placental EVs significantly inhibited ovarian cancer cell proliferation by delaying the progression of the cell cycle. We, therefore, performed this pilot in vivo study to investigate whether placental EVs can also inhibit ovarian tumour growth in a SKOV-3 human tumour xenograft model. A single intraperitoneal injection of placental EVs at 15 days post tumour implantation, significantly inhibited the growth of the tumours in our in vivo model. Signs of cellular necrosis were observed in the ovarian tumour tissues, but not in other organs collected from mice that had been treated with placental EVs. Expression of receptor-interacting kinase 1 (RIPK1) and mixed linkage kinase domain-like (MLKL), which are mediators of necroptosis were not observed in our xenografted tumours. However, extensive infiltration of CD169+ macrophages and NK cells in ovarian tumour tissues collected from placental micro-EVs treated mice were observed. We demonstrate here that inhibition of ovarian tumour growth in our xenograft model by placental EVs involves cellular necrosis and infiltration of CD169+ macrophages and NK cells into the tumour tissues.


Assuntos
Vesículas Extracelulares , Neoplasias Ovarianas , Gravidez , Humanos , Feminino , Animais , Camundongos , Placenta/metabolismo , Vesículas Extracelulares/metabolismo , Primeiro Trimestre da Gravidez , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Necrose
17.
Ann Hematol ; 102(10): 2933-2942, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37421505

RESUMO

Rhino-orbital-cerebral mucormycosis (ROCM), which is an acute fatal infectious disease with a high mortality rate, is increasingly being diagnosed in patients with hematological diseases worldwide. We aimed to investigate the clinical characteristics, treatment, and prognosis of hematological diseases complicated by ROCM. Our sample comprised a total of 60 ROCM patients with hematological diseases. The most common primary disease was acute lymphoblastic leukemia (ALL) (n=27, 45.0%), while 36 patients (60.0%) were diagnosed with a clear type of pathogen, all belonging to the Mucorales, most commonly Rhizopus (41.7%). Of the 32 patients (53.3%) who died, 19 (59.3%) died of mucormycosis, and 84.2% (n=16) of those died within 1 month. Forty-eight cases (80.0%) received antifungal treatment combined with surgical therapy, 12 of whom (25.0%) died of mucormycosis, amounting to a mortality rate that was significantly lower than in patients who received antifungal therapy alone (n=7, 58.3%) (P=0.012). The median neutrophil value of patients who underwent surgery was 0.58 (0.11-2.80) 103/µL, the median platelet value was 58.00 (17.00-93.00) 103/µL, and no surgery-related deaths were reported. Multivariate analysis showed that patient's advanced age (P=0.012, OR=1.035 (1.008-1.064)) and lack of surgical treatment (P=0.030, OR=4.971 (1.173-21.074)) were independent prognostic factors.In this study, hematological diseases associated with ROCM have a high mortality rate. Lack of surgical treatment is an independent prognostic factor for death from mucormycosis. Surgery may therefore be considered in patients with hematological disease even if their neutrophil and platelet values are lower than normal.


Assuntos
Doenças Hematológicas , Mucorales , Mucormicose , Humanos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Antifúngicos/uso terapêutico , Desbridamento , Doenças Hematológicas/complicações , Doenças Hematológicas/tratamento farmacológico
18.
Life Sci ; 329: 121934, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37460057

RESUMO

Exosomes are small extracellular vesicles that carry active substances (including proteins, lipids, and nucleic acids) and are essential for homeostasis and signal transmission. Recent studies have focused on the function of exosomal miRNAs in tumor progression. Researchers have expanded the use of exosomes and miRNAs as potential therapeutic tools and biomarkers to detect tumor progression. Immune cells, as an important part of the tumor microenvironment (TME), secrete a majority of exosome-derived miRNAs involved in the biological processes of malignancies. However, the underlying mechanisms remain unclear. Currently, there is no literature that systematically summarizes the communication of exosome-derived miRNAs between tumor cells and immune cells. Based on the cell specificity of exosome-derived miRNAs, this review provides the first comprehensive summary of the significant miRNAs from the standpoint of exosome sources, which are tumor cells and immune cells. Furthermore, we elaborated on the potential clinical applications of these miRNAs, attempting to propose existing difficulties and future possibilities in tumor diagnostics and therapy.


Assuntos
Exossomos , Vesículas Extracelulares , MicroRNAs , Neoplasias , Humanos , MicroRNAs/metabolismo , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Biomarcadores/metabolismo , Microambiente Tumoral/genética
19.
Diagnostics (Basel) ; 13(13)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37443530

RESUMO

OBJECTIVE: This study analyzed the relationship between the coronary FAI on CCTA and coronary adverse events in patients with moderate coronary artery disease based on machine learning. METHODS: A total of 172 patients with coronary artery disease with moderate or lower coronary artery stenosis were included. According to whether the patients had coronary adverse events, the patients were divided into an adverse group and a non-adverse group. The coronary FAI of patients was quantified via machine learning, and significant differences between the two groups were analyzed via t-test. RESULTS: The age difference between the two groups was statistically significant (p < 0.001). The group that had adverse reactions was older, and there was no statistically significant difference between the two groups in terms of sex and smoking status. There was no statistical significance in the blood biochemical indexes between the two groups (p > 0.05). There was a significant difference in the FAIs between the two groups (p < 0.05), with the FAI of the defective group being greater than that of the nonperforming group. Taking the age of patients as a covariate, an analysis of covariance showed that after excluding the influence of age, the FAIs between the two groups were still significantly different (p < 0.001).

20.
Eur J Gastroenterol Hepatol ; 35(8): 914-920, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37395245

RESUMO

OBJECTIVE: Patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) are characterized by severe liver function impairment, coagulation disorder, and multiple organ function impairment. The aim of this study was to explore the predictive value of antithrombin Ⅲ activity to the prognosis of HBV-ACLF patients. METHODS: A total of 186 HBV-ACLF patients were included in the analysis, and the baseline clinical data of patients were recorded to analyze the risk factors affecting the 30-day survival outcome of patients. Bacterial infection, sepsis, and hepatic encephalopathy were observed in ACLF patients. Antithrombin Ⅲ activity and serum cytokine levels were determined. RESULTS: The antithrombin Ⅲ activity of ACLF patients in the death group was significantly lower than that in the survival group, and antithrombin Ⅲ activity was independent factors affecting the 30-day outcome. The areas under the receiver operation characteristic (ROC) curve of antithrombin Ⅲ activity to predict the 30-day mortality of ACLF was 0.799. Survival analysis showed that the mortality of patients with antithrombin Ⅲ activity less than 13% was significantly increased. Patients with bacterial infection and sepsis had lower antithrombin Ⅲ activity than those without infection. Antithrombin Ⅲ activity was positively correlated with platelet count, fibrinogen, interferon (IFN)-γ, interleukin (IL)-13, IL-1ß, IL-4, IL-6, tumor necrosis factor-α, IL-23, IL-27, and IFN-α, but negatively correlated with C-reactive protein, D dimer, total bilirubin, and creatinine levels. CONCLUSION: As a natural anticoagulant, antithrombin Ⅲ can be regarded as a marker of inflammation and infection in patients with HBV-ACLF, and as a predictor of survival outcome in patients with ACLF.


Assuntos
Insuficiência Hepática Crônica Agudizada , Hepatite B Crônica , Hepatite B , Sepse , Humanos , Vírus da Hepatite B , Antitrombina III , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/etiologia , Prognóstico , Inflamação/complicações , Anticoagulantes , Sepse/complicações , Sepse/diagnóstico , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B/complicações , Hepatite B/diagnóstico , Estudos Retrospectivos
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