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2.
Chemosphere ; 316: 137871, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36646184

RESUMO

There is increasing evidence for an association of air pollutants and the incidence of chronic kidney disease, and the progression to end stage kidney disease (ESKD). Despite the global expansion of peritoneal dialysis (PD), the impact of environmental and climatic factors in PD patients has not been studied in detail. We aimed to assess the association of long-term residential exposure to air pollutants, with patient survival and incidence of hospitalizations. This was a cohort study of all prevalent ESKD patients who were stable on PD therapy for more than 90 days in our PD center from 2013/01/01 to 2018/12/31. The enrolled patients were followed until death, cessation of PD, loss to follow-up, or 2018/12/31. Time-varying pollutant exposures were modeled as the key time-dependent variables. We used time-dependent Cox model to evaluate the risk of mortality and hospitalizations associated with air pollutant exposures adjusted for potential confounders. A total of 886 subjects who meets inclusion criteria with 27,024 patient-months were modeled. Over a mean follow-up of 30.5 ± 21.3 months, we ascertained 246 cases of death and 2611 cases of hospital admission. Significant hazard ratios (HRs) were observed for all four air pollutants including PM2.5 (hazard ratio [HR] 1.27, 95% confidence interval [95%CI] 1.05-1.54), PM10 (HR 1.31, 95%CI 1.04-1.65), NO2 (HR 1.45, 95%CI 1.02-2.06), and SO2 (HR 1.20, 95%CI 1.10-1.32) in fully adjusted model, corresponding to per interquartile range µg/m3 increase of air pollutant concentrations for mortality, and non-significant HRs for incidence of hospitalization. Non-linear associations with respect to different air pollutants were observed in models for all-cause mortality and recurrent hospitalization. The estimates for mortality were significantly higher in certain groups of patients. Our findings suggest long-term exposure to ambient air pollution was associated with higher risk of all-cause mortality in PD patients, but the association with incidence of hospitalizations was less clear.

3.
J Clin Invest ; 133(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594471

RESUMO

Understanding the regulatory mechanisms of PD-L1 expression in tumors provides key clues for improving immune checkpoint blockade efficacy or developing novel oncoimmunotherapy. Here, we showed that the FDA-approved sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin dramatically suppressed PD-L1 expression and enhanced T cell-mediated cytotoxicity. Mechanistic study revealed that SGLT2 colocalized with PD-L1 at the plasma membrane and recycling endosomes and thereby prevented PD-L1 from proteasome-mediated degradation. Canagliflozin disturbed the physical interaction between SGLT2 and PD-L1 and subsequently allowed the recognition of PD-L1 by Cullin3SPOP E3 ligase, which triggered the ubiquitination and proteasome-mediated degradation of PD-L1. In mouse models and humanized immune-transformation models, either canagliflozin treatment or SGLT2 silencing significantly reduced PD-L1 expression and limited tumor progression - to a level equal to the PD-1 mAb - which was correlated with an increase in the activity of antitumor cytotoxic T cells. Notably, prolonged progression-free survival and overall survival curves were observed in the group of PD-1 mAb-treated patients with non-small cell lung cancer with high expression of SGLT2. Therefore, our study identifies a regulator of cell surface PD-L1, provides a ready-to-use small-molecule drug for PD-L1 degradation, and highlights a potential therapeutic target to overcome immune evasion by tumor cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Canagliflozina/farmacologia , Transportador 2 de Glucose-Sódio , Neoplasias Pulmonares/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Antígeno B7-H1 , Receptor de Morte Celular Programada 1 , Linhagem Celular Tumoral
4.
J Enzyme Inhib Med Chem ; 38(1): 2169282, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36656085

RESUMO

To explore the potential use of CDK inhibitors in pancreatic ductal adenocarcinoma (PDAC) therapy, a series of novel 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives was designed, synthesised, and investigated for inhibition on both CDK kinase activity and cellular proliferation of pancreatic cancer. Most of new sulphonamide-containing derivatives demonstrated strong inhibitory activity on CDK9 and obvious anti-proliferative activity in cell culture. Moreover, two new compounds suppressed cell proliferation of multiple human pancreatic cancer cell lines. The most potent compound 2g inhibited cancer cell proliferation by blocking Rb phosphorylation and induced apoptosis via downregulation of CDK9 downstream proteins Mcl-1 and c-Myc in MIA PaCa-2 cells. CDK9 knockdown experiment suggests its anti-proliferative activity is mainly mediated by CDK9. Additionally, 2g displayed moderate tumour inhibition effect in AsPC-1 derived xenograft mice model. Altogether, this study provided a new start for further optimisation to develop potential CDK inhibitor candidates for PDAC treatment by alone or combination use.


Assuntos
Antineoplásicos , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular , Neoplasias Pancreáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proliferação de Células , Apoptose , Pirimidinas/farmacologia
5.
Environ Pollut ; 320: 121036, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36623789

RESUMO

High concentrations of elemental lead (Pb) in the atmosphere pose a serious threat to human health. This study presents and summarizes data obtained from relevant literature on Pb concentrations within fine particulate matter (PM2.5) recorded in major cities in China from 2008 to 2019. An environmental health risk assessment model was then used to evaluate the health hazards of inhaling Pb among adults and children in China. Owing to the promulgation and implementation of a series of air pollution control measures, the Pb concentrations within PM2.5 measured in major cities in China showed a downward trend after peaking in 2013. The concentrations were higher in winter than in summer, and higher in northern cities than in southern cities. Although the Pb concentrations in most cities did not exceed the limit (500 ng/m3) set by China, they remained much higher than concentrations recorded in developed countries. The results of the environmental health risk analysis showed that the non-carcinogenic risk from atmospheric Pb exposure was higher in children than in adults (adult females > adult males), while the carcinogenic risk was higher in adults than in children. This study shows that even if the health risk of Pb in PM2.5 does not exceed the acceptable limit, stricter Pb pollution control measures are required to safeguard population health due to the dangers of Pb.

6.
Sci Rep ; 13(1): 1430, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36697443

RESUMO

To compare the clinical efficacy of an innovative modified single-incision technique without special extraperitoneal PORT with that of transperitoneal multi-incision robot-assisted laparoscopic radical prostatectomy and to explore the feasibility and safety of the former. A retrospective analysis was performed on 259 patients who received robot-assisted laparoscopic radical prostatectomy in the Robot Minimally Invasive Center of Sichuan Provincial People's Hospital between September 2018 and August 2021. Among them were 147 cases involving extraperitoneal single incision with no special PORT (Group A) and 112 cases involving multiple incisions by the transperitoneal method (Group B). Differences in age, PSA level, Gleason score, prostate volume, body mass index, clinical stage, lower abdominal operation history, and lymph node dissection ratio between the two groups were not statistically significant (P > 0.05). All operations were performed by the same operator. In this study, all 259 operations were completed successfully, and there was no conversion. There was no significant difference in transperitoneal blood loss, postoperative hospital stay, positive rate of incision margin, indwelling time of urinary catheter, satisfaction rate of immediate urine control, satisfaction rate of urine control 3 months after operation, positive rate of postoperative lymph node pathology or postoperative pathological stage between the two groups (P > 0.05). There were significant differences in operation time, postoperative exhaust time and incision length (P < 0.05). The modified extraperitoneal nonspecial PORT single-incision technique is safe and feasible for robot-assisted laparoscopic radical prostatectomy, and its curative effect is similar to that of transperitoneal multi-incision RARP. It has the advantages of a short operation time, less impact on the gastrointestinal tract and a more beautiful incision. The long-term effect of treatment needs to be further confirmed by prospective studies.


Assuntos
Laparoscopia , Neoplasias da Próstata , Robótica , Masculino , Humanos , Próstata/cirurgia , Próstata/patologia , Estudos Retrospectivos , Estudos Prospectivos , Prostatectomia/métodos , Laparoscopia/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia
7.
Cell Commun Signal ; 21(1): 21, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36691038

RESUMO

BACKGROUND: Previous studies have shown that depression is often accompanied by an increase in mtDNA copy number and a decrease in ATP levels; however, the exact regulatory mechanisms remain unclear. METHODS: In the present study, Western blot, cell knockdown, immunofluorescence, immunoprecipitation and ChIP-qPCR assays were used to detect changes in the Ahi1/GR-TFAM-mtDNA pathway in the brains of neuronal Abelson helper integration site-1 (Ahi1) KO mice and dexamethasone (Dex)-induced mice to elucidate the pathogenesis of depression. In addition, a rescue experiment was performed to determine the effects of regular exercise on the Ahi1/GR-TFAM-mtDNA-ATP pathway and depression-like behavior in Dex-induced mice and Ahi1 KO mice under stress. RESULTS: In this study, we found that ATP levels decreased and mitochondrial DNA (mtDNA) copy numbers increased in depression-related brain regions in Dex-induced depressive mice and Ahi1 knockout (KO) mice. In addition, Ahi1 and glucocorticoid receptor (GR), two important proteins related to stress and depressive behaviors, were significantly decreased in the mitochondria under stress. Intriguingly, GR can bind to the D-loop control region of mitochondria and regulate mitochondrial replication and transcription. Importantly, regular exercise significantly increased mitochondrial Ahi1/GR levels and ATP levels and thus improved depression-like behaviors in Dex-induced depressive mice but not in Ahi1 KO mice under stress. CONCLUSIONS: In summary, our findings demonstrated that the mitochondrial Ahi1/GR complex and TFAM coordinately regulate mtDNA copy numbers and brain ATP levels by binding to the D-loop region of mtDNA Regular exercise increases the levels of the mitochondrial Ahi1/GR complex and improves depressive behaviors. Video Abstract.


Assuntos
DNA Mitocondrial , Receptores de Glucocorticoides , Camundongos , Animais , DNA Mitocondrial/metabolismo , Receptores de Glucocorticoides/metabolismo , Variações do Número de Cópias de DNA , Mitocôndrias/metabolismo , Camundongos Knockout , Encéfalo/metabolismo , Trifosfato de Adenosina/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética
8.
Radiat Oncol ; 18(1): 3, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604687

RESUMO

OBJECTIVE: Anatomical variations existing in cervical cancer radiotherapy treatment can be monitored by cone-beam computed tomography (CBCT) images. Deformable image registration (DIR) from planning CT (pCT) to CBCT images and synthetic CT (sCT) image generation based on CBCT are two methods for improving the quality of CBCT images. This study aims to compare the accuracy of these two approaches geometrically and dosimetrically in cervical cancer radiotherapy. METHODS: In this study, 40 paired pCT-CBCT images were collected to evaluate the accuracy of DIR and sCT generation. The DIR method was based on a 3D multistage registration network that was trained with 150 paired pCT-CBCT images, and the sCT generation method was performed based on a 2D cycle-consistent adversarial network (CycleGAN) with 6000 paired pCT-CBCT slices for training. Then, the doses were recalculated with the CBCT, pCT, deformed pCT (dpCT) and sCT images by a GPU-based Monte Carlo dose code, ArcherQA, to obtain DoseCBCT, DosepCT, DosedpCT and DosesCT. Organs at risk (OARs) included small intestine, rectum, bladder, spinal cord, femoral heads and bone marrow, CBCT and pCT contours were delineated manually, dpCT contours were propagated through deformation vector fields, sCT contours were auto-segmented and corrected manually. RESULTS: The global gamma pass rate of DosesCT and DosedpCT was 99.66% ± 0.34%, while that of DoseCBCT and DosedpCT was 85.92% ± 7.56% at the 1%/1 mm criterion and a low-dose threshold of 10%. Based on DosedpCT as uniform dose distribution, there were comparable errors in femoral heads and bone marrow for the dpCT and sCT contours compared with CBCT contours, while sCT contours had lower errors in small intestine, rectum, bladder and spinal cord, especially for those with large volume difference of pCT and CBCT. CONCLUSIONS: For cervical cancer radiotherapy, the DIR method and sCT generation could produce similar precise dose distributions, but sCT contours had higher accuracy when the difference in planning CT and CBCT was large.


Assuntos
Tomografia Computadorizada de Feixe Cônico Espiral , Neoplasias do Colo do Útero , Feminino , Humanos , Dosagem Radioterapêutica , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Órgãos em Risco , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Processamento de Imagem Assistida por Computador/métodos
9.
J Phys Chem Lett ; : 863-869, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36657017

RESUMO

Ambient-pressure X-ray photoelectron spectroscopy (APXPS) provides an effective way of tackling the challenge of detecting chemical states within complex systems. Here a fundamental understanding of the core-level shift (CLS) of water in the liquid/gas phase observed via APXPS is obtained with computational modeling at the molecular and electronic levels. The CLS value of ∼2 eV derived from experiments is reproduced by modeling in terms of the total shift and photon energy dependence. The contributions of collective electrical effects, including electrostatic potential, orbital deformation, and electronic polarization, to the CLS were further analyzed and discussed. Our results show that the CLS is dominated by the final state effect due to electronic polarization of the surrounding molecules following photoionization, while the peak broadening is mainly determined by the electrostatic potential, which belongs to an initial state effect. The physical insights and computational approaches could be further applied to study more complex molecules or materials.

10.
Acta Pharmacol Sin ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658427

RESUMO

Acute kidney injury (AKI) caused by anti-tumor drugs, such as cisplatin, is a severe complication with no effective treatment currently, leading to the reduction or discontinuation of chemotherapy. Natural products or herbal medicines are gradually considered as promising agents against cisplatin-induced AKI with the advantages of multi-targeting, multi-effects, and less resistance. In this study, we investigated the effects of kaempferide, a natural flavonoid extracted from the rhizome of Kaempferia galanga, in experimental AKI models in vitro and in vivo. We first conducted pharmacokinetic study in mice and found a relative stable state of kaempferide with a small amount of conversion into kaempferol. We showed that both kaempferide (10 µM) and kaempferol (10 µM) significantly inhibited cisplatin-caused injuries in immortalized proximal tubule epithelial cell line HK-2. In AKI mice induced by injection of a single dose of cisplatin (15 mg/kg), oral administration of kaempferide (50 mg/kg) either before or after cisplatin injection markedly improved renal function, and ameliorated renal tissue damage. We demonstrated that kaempferide inhibited oxidative stress and induced autophagy in cisplatin-treated mice and HK-2 cells, thus increasing tubular cell viability and decreasing immune responses to attenuate the disease progression. In addition, treatment with kaempferide significantly ameliorated ischemia-reperfusion-induced renal injury in vitro and in vivo. We conclude that kaempferide is a promising natural product for treating various AKI. This study has great implications for promotion of its use in healthcare products, and help to break through the limited use of cisplatin in the clinic.

11.
Water Res ; 231: 119609, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36669307

RESUMO

Nano zero-valent iron (NZVI) has been widely used to improve refractory wastewater treatment. However, the rapid dissolution of NZVI causes a waste of resources and an unstable bioaugmentation. Herein, to verify the essential role of slow release of NZVI on biological systems, a core-shell structured Fe@C composite was developed to demonstrate the long-term feasibility of Fe@C for enhancing azo dye biodegradation in comparison to a mixture of NZVI and carbon powder (Fe+C). The 150 days of long-term reactor operation showed that, although both Fe@C and Fe+C enhanced azo dye degradation, the former achieved a better performance than the latter. The strengthening effect of Fe@C was also more durable and stable than Fe+C. It may be due to the fact that the carbon layer of Fe@C could interact with extracellular polymeric substances (EPS) through physical adsorption and chemical bonding to form a stable buffer to regulate NZVI dissolution. The buffer layer could not only regulate the attack of H+ on NZVI to reduce its dissolution rate but also complex released Fe2+ and neutralize OH- to alleviate the passivation layer formed on the NZVI surface. Moreover, microbial community analysis indicated that both Fe@C and Fe+C increased the abundance of fermentative bacteria (e.g., Bacteroidetes_vadinHA17, Propionicicella) and methanogens (e.g., Methanobacterium), but only Fe@C promoted the growth of azo dye degraders (e.g., Clostridium, Geobacter). Metatranscriptomic analysis further revealed that only Fe@C could substantially stimulate the expression of azoreductase and redox mediator (e.g., riboflavin, ubiquinone) biosynthesis involved in the extracellular degradation of azo dye. This work provides novel insights into the bioaugmentation of Fe@C for refractory wastewater treatment.

12.
Brief Bioinform ; 24(1)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36617209

RESUMO

Recent studies have shown that the expression of circRNAs would affect drug sensitivity of cells and thus significantly influence the efficacy of drugs. Traditional biomedical experiments to validate such relationships are time-consuming and costly. Therefore, developing effective computational methods to predict potential associations between circRNAs and drug sensitivity is an important and urgent task. In this study, we propose a novel method, called MNGACDA, to predict possible circRNA-drug sensitivity associations for further biomedical screening. First, MNGACDA uses multiple sources of information from circRNAs and drugs to construct multimodal networks. It then employs node-level attention graph auto-encoders to obtain low-dimensional embeddings for circRNAs and drugs from the multimodal networks. Finally, an inner product decoder is applied to predict the association scores between circRNAs and drug sensitivity based on the embedding representations of circRNAs and drugs. Extensive experimental results based on cross-validations show that MNGACDA outperforms six other state-of-the-art methods. Furthermore, excellent performance in case studies demonstrates that MNGACDA is an effective tool for predicting circRNA-drug sensitivity associations in real situations. These results confirm the reliable prediction ability of MNGACDA in revealing circRNA-drug sensitivity associations.


Assuntos
RNA Circular , RNA Circular/genética
13.
Sensors (Basel) ; 23(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36679487

RESUMO

Accurate segmentation of the left atrial structure using magnetic resonance images provides an important basis for the diagnosis of atrial fibrillation (AF) and its treatment using robotic surgery. In this study, an image segmentation method based on sequence relationship learning and multi-scale feature fusion is proposed for 3D to 2D sequence conversion in cardiac magnetic resonance images and the varying scales of left atrial structures within different slices. Firstly, a convolutional neural network layer with an attention module was designed to extract and fuse contextual information at different scales in the image, to strengthen the target features using the correlation between features in different regions within the image, and to improve the network's ability to distinguish the left atrial structure. Secondly, a recurrent neural network layer oriented to two-dimensional images was designed to capture the correlation of left atrial structures in adjacent slices by simulating the continuous relationship between sequential image slices. Finally, a combined loss function was constructed to reduce the effect of positive and negative sample imbalance and improve model stability. The Dice, IoU, and Hausdorff distance values reached 90.73%, 89.37%, and 4.803 mm, respectively, based on the LASC2013 (left atrial segmentation challenge in 2013) dataset; the corresponding values reached 92.05%, 89.41% and 9.056 mm, respectively, based on the ASC2018 (atrial segmentation challenge at 2018) dataset.


Assuntos
Fibrilação Atrial , Procedimentos Cirúrgicos Robóticos , Humanos , Fibrilação Atrial/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Redes Neurais de Computação , Átrios do Coração/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos
14.
Vaccines (Basel) ; 11(1)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36680029

RESUMO

Chinese-Americans are one of the largest groups of Asian-Americans in the US with distinctive behavioral and cultural characteristics that influence health service use. Although Chinese-Americans have significantly higher COVID-19-related mortality rates, relative to other racial and ethnic groups, limited literature is available examining their willingness to accept the COVID-19 vaccine. With recent development of the combination influenza-COVID-19 vaccine by biotechnology companies to mitigate COVID-19 infection, we examined factors associated with Chinese-Americans' acceptance of hypothetical annual doses of COVID-19 vaccination before the vaccine rollout. A total of 241 Chinese-Americans who received at least one dose of the COVID-19 vaccine completed an online questionnaire developed and based on health behavior theories. Our results indicated that Chinese-American participants who were satisfied with their prior COVID-19 vaccination experience, who had more accurate knowledge and perceived higher susceptibility of getting COVID-19, were more willing to receive the annual COVID-19 vaccine in the future. The findings of our current study may be used to guide the development of strategic messages to promote uptake of the annual COVID-19 vaccine by Chinese-Americans in the U.S.

15.
Org Lett ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693162

RESUMO

The reductive cleavage of C(Ar)-X bonds is the key step for the cross coupling of Ar-X with other groups. In this work, under the irradiation of 407 nm LEDs using sodium formate as reductant and thiol as hydrogen atom transfer agent, a variety of (hetero)aryl chlorides, bromides, and iodides could be reduced to corresponding (hetero)arenes. The key intermediates, aryl radicals, could be trapped by either hydrogen, phosphite, or borates. The same reduction conditions can be extended to the deprotection of sulfonamides.

16.
Chemistry ; 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36695295

RESUMO

A series of zigzag-edged polycyclic aromatic hydrocarbons (PAHs) (Z1-Z3) were synthesized from 2,12-dibromo-7,14-diphenyl-benzo[m]tetraphene (9) as a versatile building block. Their structures were unambiguously confirmed by laser desorption/ionization time-of-flight mass spectrometry, 1H NMR, Raman, and Fourier-transformed infrared (FTIR) spectroscopies as well as scanning tunneling microscopy. The fingerprint vibrational modes were elucidated with theoretical support. The edge- and size-dependent optical properties were characterized by UV-Vis absorption and fluorescence spectroscopy and DFT calculations. Moreover, ultrafast transient absorption spectroscopy revealed distinct modulation of the photophysical properties upon π-extension from Z1 to Z2, the latter having a gulf edge.

17.
Hepatology ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36633260

RESUMO

BACKGROUND AND AIMS: Nicotinamide N-methyltransferase (NNMT), an enzyme responsible for the methylation of nicotinamide, is involved in many metabolic pathways in adipose tissue and the liver. However, the role of NNMT in editing the tumor immune microenvironment is not well understood. APPROACH AND RESULTS: Here, we identified that NNMT can promote IL6 and CM-CSF expression by decreasing the H3K27me3 levels on the promoters of IL6 and CSF2 (encoding GM-CSF) and CCAAT/Enhancer Binding Protein (CEBPB), an essential transcription factor for IL6 expression, thus promoting differentiation of macrophages into M2 type tumor-associated macrophages (TAMs) and generation of myeloid-derived suppressor cells (MDSCs) from peripheral blood mononuclear cells. Treatment of xenografted tumor models overexpressing NNMT gallbladder carcinoma (GBC) cells with the NNMT inhibitor JBSNF-000088 resulted in compromised tumor development and decreased expression levels of IL6, CSF2, TAM marker CD206 and MDSC marker CD33 but increased expression levels of CD8. In addition, elevated expression of NNMT in tumors of patients with GBC was correlated with increased expression levels of CD206 and CD33 but with decreased levels of CD8 and survival of patients. CONCLUSIONS: These data highlight the critical role of NNMT in GBC progression. Inhibition of NNMT by JBSNF-000088 is a potential molecular target for GBC immunotherapy.

18.
Environ Sci Technol ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633507

RESUMO

Recently, a study found that aromatic DBP fractions dominate the overall toxicity of chlorinated drinking water. However, key toxicity drivers have not been reported via comprehensive evaluation based on the formation of aliphatic and aromatic DBPs in drinking water. In this study, the occurrence of 37 aliphatic and 19 aromatic DBPs in drinking samples with different water characteristics collected in a Chinese megacity was explored. According to the individual DBP concentrations and cytotoxicity potencies as well as the "TIC-Tox" method, haloacetonitriles and halonitrophenols were found to be the toxicity drivers among the measured aliphatic and aromatic DBPs, respectively. However, when aromatic and aliphatic DBPs are taken into consideration together, aliphatic DBPs were calculated to present higher toxicity contribution than aromatic DBPs, which is inconsistent with the previous study. TOX showed significant positive correlations with most aliphatic DBPs but no aromatic DBPs, and the overall toxicity of the water sample concentrates is significantly related to the total calculated cytotoxicity and aliphatic DBPs, suggesting that current selected aromatic DBPs are insufficient to represent the overall aromatic DBPs. UV254 and DOC rather than SUVA are better surrogates for predicting DBP formation potential for DOM with a lower humification degree as indicated by fluorescence results.

19.
Blood Purif ; : 1-7, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599318

RESUMO

Encapsulating peritoneal sclerosis (EPS) is an uncommon and harmful complication which may cause destructive outcomes. Matrix metalloproteinase-2 (MMP-2) as a protease can reduce constituents of the extracellular matrix and play a crucial role in the progression of EPS. As a new biomarker, MMP-2 may improve the detection rate of EPS patients in clinical work. In this review, we summarize the recent study of MMP-2 in different etiologies and the assessment of its application value and draw attention to its future directions.

20.
Int J Biol Sci ; 19(1): 167-182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36594094

RESUMO

Drug resistance presents a major obstacle in the treatment of genitourinary cancers. Exosomes as the medium of intercellular communication serve important biological functions and play essential roles in pathological processes, including drug response. Through the transfer of bioactive cargoes, exosomes can modulate drug resistance via multiple mechanisms. This review attempts to elucidate the mechanisms of exosomal cargoes with reference to tumor drug resistance, their role in genitourinary cancers, and their potential clinical applications as candidate biomarkers in liquid biopsy.


Assuntos
Exossomos , Neoplasias , Neoplasias Urogenitais , Humanos , Biomarcadores , Resistencia a Medicamentos Antineoplásicos/genética , Biópsia Líquida , Neoplasias Urogenitais/patologia , Neoplasias/tratamento farmacológico , Biomarcadores Tumorais
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