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1.
Environ Pollut ; 351: 124084, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38697245

RESUMO

Due to the potential impacts of microplastics (MPs) and nanoplastics (NPs) on algal growth and thereby affect the climate-relevant substances, dimethylsulfoniopropionate (DMSP) and dimethyl sulfide (DMS), we studied the polystyrene (PS) MPs and NPs of 1 µm and 80 nm impacts on the growth, chlorophyll content, reactive oxygen species (ROS), antioxidant enzyme activity, and DMS/DMSP production in Emiliania huxleyi. E. huxleyi is a prominent oceanic alga that plays a key role in DMS and DMSP production. The results revealed that high concentrations of MPs and NPs inhibited the growth, carotenoid (Car), and Chl a concentrations of E. huxleyi. However, short-time exposure to low concentrations of PS MPs and NPs stimulated the growth of E. huxleyi. Furthermore, high concentrations of MPs and NPs resulted in an increase in the superoxide anion radical (O2.-) production rate and a decrease in the malondialdehyde (MDA) content compared with the low concentrations. Exposure to MPs and NPs at 5 mg L-1 induced superoxide dismutase (SOD) activity as a response to scavenging ROS. High concentrations of MPs and NPs significantly inhibited the production of DMSP and DMS. The findings of this study support the potential ecotoxicological impacts of MPs and NPs on algal growth, antioxidant system, and dimethylated sulfur compounds production, which maybe potentially impact the global climate.


Assuntos
Antioxidantes , Haptófitas , Espécies Reativas de Oxigênio , Sulfetos , Compostos de Sulfônio , Poluentes Químicos da Água , Antioxidantes/metabolismo , Compostos de Sulfônio/metabolismo , Haptófitas/crescimento & desenvolvimento , Haptófitas/metabolismo , Haptófitas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Clorofila/metabolismo , Superóxido Dismutase/metabolismo , Nanopartículas/toxicidade , Poliestirenos/toxicidade
2.
Sleep Breath ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38772968

RESUMO

PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.

3.
Physiol Meas ; 45(6)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38772397

RESUMO

Objective. Acute hypotension episode (AHE) is one of the most critical complications in intensive care unit (ICU). A timely and precise AHE prediction system can provide clinicians with sufficient time to respond with proper therapeutic measures, playing a crucial role in saving patients' lives. Recent studies have focused on utilizing more complex models to improve predictive performance. However, these models are not suitable for clinical application due to limited computing resources for bedside monitors.Approach. To address this challenge, we propose an efficient lightweight dilated shuffle group network. It effectively incorporates shuffling operations into grouped convolutions on the channel and dilated convolutions on the temporal dimension, enhancing global and local feature extraction while reducing computational load.Main results. Our benchmarking experiments on the MIMIC-III and VitalDB datasets, comprising 6036 samples from 1304 patients and 2958 samples from 1047 patients, respectively, demonstrate that our model outperforms other state-of-the-art lightweight CNNs in terms of balancing parameters and computational complexity. Additionally, we discovered that the utilization of multiple physiological signals significantly improves the performance of AHE prediction. External validation on the MIMIC-IV dataset confirmed our findings, with prediction accuracy for AHE 5 min prior reaching 93.04% and 92.04% on the MIMIC-III and VitalDB datasets, respectively, and 89.47% in external verification.Significance. Our study demonstrates the potential of lightweight CNN architectures in clinical applications, providing a promising solution for real-time AHE prediction under resource constraints in ICU settings, thereby marking a significant step forward in improving patient care.


Assuntos
Hospitalização , Hipotensão , Unidades de Terapia Intensiva , Redes Neurais de Computação , Humanos , Hipotensão/fisiopatologia , Hipotensão/diagnóstico , Doença Aguda
4.
Artigo em Inglês | MEDLINE | ID: mdl-38606576

RESUMO

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

5.
Mar Environ Res ; 197: 106481, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38593647

RESUMO

Marine distribution of dimethylsulfoniopropionate (DMSP) and its cleavage product dimethyl sulfide (DMS) is greatly affected by the community structures of bacteria, phytoplankton, and zooplankton. Spatial distributions of dissolved and particulate DMSP (DMSPd,p), and DMS were measured and their relationships with DMSP lyase activity (DLA), abundance of DMSP-consuming bacteria (DCB), and the community structures of phytoplankton, zooplankton, and bacteria were determined during summer in the South China Sea (SCS). The depth distributions of DMSPd,p exhibited a similar trend with Chl a, reaching their maxima in the mixing layer. The DMS concentration was positively correlated with DCB abundance and DLA, indicating that DCB and DMSP lyase had a significant effect on DMS production. High DMS concentrations in the horizontal distribution coincided with high DCB abundance and DLA and may be due to the rapid growth of phytoplankton resulting from the high dissolved inorganic nitrogen concentration brought by the cold vortices. Moreover, the highest copepod abundance at station G3 coincided with the highest DMS concentrations there among stations B4, F2, and G3. These results suggest that copepod may play an important role in DMS production. The bacterial SAR11 clade was positively correlated with DLA, indicating its significant contribution to DMSP degradation in the SCS. These findings contribute to the understanding of the effect of the community assemblage on DMSP/DMS distributions in the SCS dominated by mesoscale vortices.


Assuntos
Água do Mar , Compostos de Sulfônio , Animais , Água do Mar/química , Enxofre/metabolismo , Compostos de Sulfônio/química , Compostos de Sulfônio/metabolismo , Sulfetos/metabolismo , Bactérias/metabolismo , Fitoplâncton , China , Zooplâncton/metabolismo
6.
Biochem Biophys Res Commun ; 712-713: 149941, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38643718

RESUMO

While diosgenin has been demonstrated effective in various cardiovascular diseases, its specific impact on treating heart attacks remains unclear. Our research revealed that diosgenin significantly improved cardiac function in a myocardial infarction (MI) mouse model, reducing cardiac fibrosis and cell apoptosis while promoting angiogenesis. Mechanistically, diosgenin upregulated the Hand2 expression, promoting the proliferation and migration of endothelial cells under hypoxic conditions. Acting as a transcription factor, HAND2 activated the angiogenesis-related gene Aggf1. Conversely, silencing Hand2 inhibited the diosgenin-induced migration of hypoxic endothelial cells and angiogenesis. In summary, these findings provide new insights into the protective role of diosgenin in MI, validating its effect on angiogenic activity and providing a theoretical basis for clinical treatment strategies.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Diosgenina , Camundongos Endogâmicos C57BL , Infarto do Miocárdio , Neovascularização Fisiológica , Animais , Diosgenina/farmacologia , Diosgenina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Neovascularização Fisiológica/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Masculino , Camundongos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Angiogênese
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124312, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38688210

RESUMO

The ubiquity of diverse material entities in environmental matrices renders the deployment of unifunctional fluorescent indicators inadequate. Consequently, this study introduces a ratiometric dual-emission fluorescent sensor (Probe CP), synthesized by conjugating phenothiazine coumarin to hydroxycoumarin through a piperazine linker for concurrent detection of HClO and H2S. Upon interaction with HClO, the phenothiazine unit's sulfur atom undergoes oxidation to sulfoxide, facilitating a shift from red to green fluorescence in a ratiometric manner. Concurrently, at the opposite terminus of Probe CP, 2,4-dinitroanisole serves as the reactive moiety for H2S recognition; it restores the blue emission characteristic of 7-hydroxycoumarin while maintaining the red fluorescence emanating from phenothiazine coumarin as an internal standard for ratio-based assessment. Exhibiting elevated specificity and sensitivity coupled with minimal detection thresholds (0.0506 µM for HClO and 1.7292 µM for H2S) alongside rapid equilibration periods (3 min for HClO and half an hour for H2S), this sensor was efficaciously employed in cellular environments and within zebrafish models as well as imaging applications pertaining to alcohol-induced hepatic injury in murine subjects.


Assuntos
Cumarínicos , Corantes Fluorescentes , Sulfeto de Hidrogênio , Fenotiazinas , Peixe-Zebra , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Animais , Fenotiazinas/química , Fenotiazinas/síntese química , Cumarínicos/química , Cumarínicos/síntese química , Sulfeto de Hidrogênio/análise , Camundongos , Espectrometria de Fluorescência/métodos , Humanos
8.
Chemosphere ; 350: 141091, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171399

RESUMO

Stabilization techniques are vital in controlling Cd soil pollution. Nano zero valent iron (nZVI) has been extensively utilized for Cd remediation owing to its robust adsorption and reactivity. However, the environmental stress-induced stability of Cd after nZVI addition remains unclear. A pot experiment was conducted to evaluate the Cd bioavailability in continuously flooded (130 d) soil after stabilization with nZVI. The findings indicated that nZVI application did not result in a decline in Cd concentration in rice, as compared to the no-nZVI control. Additionally, nZVI simultaneously increased the available Cd concentration, iron-manganese oxide-bound (OX) Mn fraction, and relative abundance of Fe(III)-reducing bacteria, but it decreased OX-Cd and Mn availability in soil. Cadmium in rice tissues was positively correlated with the available Cd in soil. The results of subsequent adsorption tests demonstrated that CdO was the product of Cd adsorption by the nZVI aging products. Conversely, Mn2+ decreased the adsorption capacity of Cd-containing solutions. These results underscore the crucial role of both biotic and abiotic factors in undermining the stabilization of nZVI under continuous flooding conditions. This study offers novel insights into the regulation of nZVI-mediated Cd stabilization efficiency in conjunction with biological inhibitors and functional modification techniques.


Assuntos
Recuperação e Remediação Ambiental , Poluentes do Solo , Ferro , Compostos Férricos , Cádmio/análise , Solo , Poluentes do Solo/análise
9.
Artigo em Inglês | MEDLINE | ID: mdl-38284738

RESUMO

Ferroptosis is a newly discovered form of programmed cell death characterized by iron overload, ROS accumulation, and lipid peroxidation. It is distinguished by unique morphological, biochemical, and genetic features and stands apart from other known regulated cell death mechanisms. Studies have demonstrated a close association between ferroptosis and various cancers, including liver cancer, lung cancer, renal cell carcinoma, colorectal cancer, pancreatic cancer, and ovarian cancer. Inducing ferroptosis has shown promising results in inhibiting tumor growth and reversing tumor progression. However, the challenge lies in regulating ferroptosis in vivo due to the scarcity of potent compounds that can activate it. Integrating emerging biomedical discoveries and technological innovations with conventional therapies is imperative. Notably, considerable progress has been made in cancer treatment by leveraging immunotherapy and nanotechnology to trigger ferroptosis. This review explores the relationship between ferroptosis and emerging immunotherapies and nanotechnologies, along with their potential underlying mechanisms, offering valuable insights for developing novel cancer treatment strategies.

11.
Environ Pollut ; 344: 123308, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38185352

RESUMO

Microplastics (MPs) and nanoplastics (NPs) have gained global concern due to their detrimental effects on marine organisms. We investigated the effects of 80 nm polystyrene (PS) NPs on life history traits, ingestion, and dimethyl sulfide (DMS) and dimethylsulfoniopropionate (DMSP) production in the rotifer Brachionus plicatilis. Fluorescently labeled 80 nm PS NPs were ingested by the rotifer B. plicatilis and accumulated in the digestive tract. The lethal rates of B. plicatilis exposed to NPs were dose-dependent. High concentrations of PS NPs exposure had negative effects on developmental duration, leading to prolonged embryonic development and pre-reproductive periods, shortened reproductive period, post-reproductive period, and lifespan in B. plicatilis. High concentrations of PS NPs exposure inhibited life table demographic parameters such as age-specific survivorship and fecundity, generation time, net reproductive rate, and life expectancy. Consequently, the population of B. plicatilis was adversely impacted. Furthermore, exposure to PS NPs resulted in a reduced ingestion rate in B. plicatilis, as well as a decreased in DMS, particulate DMSP (DMSPp) concentration, and DMSP lyase activity (DLA), which exhibited a dose-response relationship. B. plicatilis grazing promoted DLA and therefore increased DMS production. PS NPs exposure caused a decline in the increased DMS induced by rotifer grazing. Our results help to understand the ecotoxicity of NPs on rotifer and their impact on the biogeochemical cycle of dimethylated sulfur compounds.


Assuntos
Características de História de Vida , Rotíferos , Sulfetos , Poluentes Químicos da Água , Animais , Microplásticos , Plásticos/farmacologia , Poliestirenos/farmacologia , Ingestão de Alimentos , Poluentes Químicos da Água/toxicidade
12.
J Clin Endocrinol Metab ; 109(2): 351-360, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-37708346

RESUMO

CONTEXT: Intraoperative hemodynamic instability (HDI) can lead to cardiovascular and cerebrovascular complications during surgery for pheochromocytoma/paraganglioma (PPGL). OBJECTIVES: We aimed to assess the risk of intraoperative HDI in patients with PPGL to improve surgical outcome. METHODS: A total of 199 consecutive patients with PPGL confirmed by surgical pathology were retrospectively included in this study. This cohort was separated into 2 groups according to intraoperative systolic blood pressure, the HDI group (n = 101) and the hemodynamic stability (HDS) group (n = 98). It was also divided into 2 subcohorts for predictive modeling: the training cohort (n = 140) and the validation cohort (n = 59). Prediction models were developed with both the ensemble machine learning method (EL model) and the multivariate logistic regression model using body composition parameters on computed tomography, tumor radiomics, and clinical data. The efficiency of the models was evaluated with discrimination, calibration, and decision curves. RESULTS: The EL model showed good discrimination between the HDI group and HDS group, with an area under the curve of (AUC) of 96.2% (95% CI, 93.5%-99.0%) in the training cohort, and an AUC of 93.7% (95% CI, 88.0%-99.4%) in the validation cohort. The AUC values from the EL model were significantly higher than the logistic regression model, which had an AUC of 74.4% (95% CI, 66.1%-82.6%) in the training cohort and an AUC of 74.2% (95% CI, 61.1%-87.3%) in the validation cohort. Favorable calibration performance and clinical applicability of the EL model were observed. CONCLUSION: The EL model combining preoperative computed tomography-based body composition, tumor radiomics, and clinical data could potentially help predict intraoperative HDI in patients with PPGL.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Doenças Vasculares , Humanos , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/cirurgia , Radiômica , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Composição Corporal , Aprendizado de Máquina
13.
Gastric Cancer ; 27(1): 49-71, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37897508

RESUMO

BACKGROUND: Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been demonstrated to play vital roles in development and progression of tumors such as gastric cancer (GC). However, the detailed molecular mechanism of OIP5-AS1 has not been completely elucidated. Our study aimed to investigate the role and the epigenetic regulation mechanism of OIP5-AS1 in GC. METHODS: OIP5-AS1 expression in GC tissues was detected by RT-qPCR. Loss- and gain-of-function experiments were conducted to assess the biological function of OIP5-AS1 in vitro and in vivo. The interaction of OIP5-AS1 with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) or heterogeneous nuclear nucleoprotein A1 (hnRNPA1) was verified by bioinformatics analysis, RNA pull-down assays, and RNA immunoprecipitation assays. RESULTS: In this study, we identified that OIP5-AS1 is specifically overexpressed in GC tumor tissues and cell lines and correlated with a poor prognosis. The loss of OIP5-AS1 suppressed the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and glycolysis of GC cells, but the ectopic expression of OIP5-AS1 had the opposite impact. Meanwhile, knockdown of OIP5-AS1 inhibited tumor growth in patient-derived xenograft models, as well as repressed tumor metastasis. Mechanistically, IGF2BP3 could bind to OIP5-AS1 by N6-methyladenosine (m6A) modification sites on OIP5-AS1, thereby stabilizing OIP5-AS1. Moreover, OIP5-AS1 prevented Trim21-mediated ubiquitination and degradation of hnRNPA1, stabilizing hnRNPA1 protein and promoting the malignant progression of GC by regulating PKM2 signaling pathway. CONCLUSIONS: In conclusion, this study highlighted that OIP5-AS1 is an oncogenic m6A-modified long non-coding RNA (lncRNA) in GC and that IGF2BP3/OIP5-AS1/hnRNPA1 axis may provide a potential diagnostic or prognostic target for GC.


Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Glicólise , MicroRNAs/genética , Neoplasias Gástricas/genética
14.
Int Immunopharmacol ; 127: 111372, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38118314

RESUMO

Mesangial proliferative glomerulonephritis (MsPGN) and its related rat model Thy-1 nephritis (Thy-1N) are associated with C5b-9 deposition and are characterized by proliferation of glomerular mesangial cell (GMC) and expansion of extracellular matrix (ECM) expansion, alongside overexpression of multiple growth factors. Although fibroblast growth factor 1 (FGF1), platelet-derived growth factor alpha (PDGFα), and transforming growth factor beta 1 (TGF-ß1) are well known for their proproliferative and profibrotic roles, the molecular mechanisms responsible for regulating the expression of these growth factors have not been thoroughly elucidated. In this study, we found that sublytic C5b-9 induction of sex-determining region Y-box 9 (SOX9) transactivated FGF1, PDGFα, and TGF-ß1 genes in GMCs, resulting in a significant increase in their mRNA and protein levels. Besides, sublytic C5b-9 induction of activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylated SOX9 at serine 181 and serine 64, which enhanced SOX9's ability to transactivate FGF1, PDGFα, and TGF-ß1 genes in GMCs. Furthermore, we demonstrated that inhibiting ERK1/2 activation or silencing either ERK1/2 or SOX9 gene led to reduced SOX9 phosphorylation, decreased generation of FGF1, PDGFα, and TGF-ß1, and ameliorated glomerular injury in rat Thy-1N. Overall, these findings suggest that expression of FGF1, PDGFα, and TGF-ß1 is promoted by ERK1/2-mediated phosphorylation of SOX9, which may provide a valuable insight into the pathogenesis of MsPGN and offer a potential target for the development of novel treatment strategies for MsPGN.


Assuntos
Fator 1 de Crescimento de Fibroblastos , Nefrite , Ratos , Animais , Fator 1 de Crescimento de Fibroblastos/genética , Fator 1 de Crescimento de Fibroblastos/metabolismo , Fosforilação , Ratos Sprague-Dawley , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Sistema de Sinalização das MAP Quinases , Nefrite/metabolismo , Serina/metabolismo
15.
Pak J Med Sci ; 39(6): 1847-1852, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37936761

RESUMO

Objectives: To investigate the impact of combining lenvatinib with transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC). Methods: This was a retrospective observational study which reviewed the medical records of 103 unresectable HCC patients from January 2017 to June 2020 in The First Affiliated Hospital of Soochow University. It included 46 patients who received TACE plus lenvatinib and 57 patients who received TACE alone. The levels of serum indicators, clinical effect, adverse events, overall survival (OS), and progression-free survival (PFS) were compared between the two groups. Results: AFP and VEGF levels in the TACE+lenvatinib group post-treatment were significantly lower than the TACE group (P<0.05). The clinical efficacy in the TACE+lenvatinib group (69.57%) was higher than that in the TACE group (40.35%) post-treatment (P<0.05). There were significant differences in hypertension, diarrhea, and bleeding (gingiva) between the two groups (P<0.05). There were no significant differences in one or two year PFS rate or one year OS between groups (P>0.05), while the two years survival rate in the TACE+lenvatinib group was significantly higher than that in the TACE group (P<0.05). Conclusions: TACE combined with lenvatinib have a high clinical effective rate, with reduced AFP and VEGF levels, higher two year survival rate, and acceptable incidence of adverse events.

16.
Endocr Relat Cancer ; 30(12)2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37902037

RESUMO

The biochemical phenotype of paragangliomas (PGLs) is highly dependent on the underlying genetic background and tumor location. PGLs at extra-adrenal locations usually do not express phenylethanolamine N-methyltransferase (PNMT), the enzyme required for epinephrine production, which was explained by the absence of glucocorticoids. PGLs with pathogenic variants (PVs) in Harvey rat sarcoma viral oncogene homolog (HRAS) can occur in or outside of the adrenal, but always synthesize epinephrine independently of the localization. Here, we characterize the signaling pathways through which PVs in HRAS influence PNMT expression. Catecholamines, cortisol, and transcriptional features of PGL tissues with known genetic background were analyzed. Genetically modified rat pheochromocytoma cells carrying PVs in Hras were generated and analyzed for regulation of Pnmt expression. Elevated epinephrine contents in PGLs with PVs in HRAS were accompanied by enrichment in mitogen-activated protein kinase (MAPK) signaling compared to PGLs with PVs in genes that activate hypoxia pathways. In vitro, Hras PVs increased Pnmt expression and epinephrine biosynthesis through increased phosphorylation of stimulatory protein 1 via MAPK signaling. Here, we provide a molecular mechanism that explains the PV-dependent epinephrine production of PGLs.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/genética , Proteínas Proto-Oncogênicas p21(ras) , Neoplasias das Glândulas Suprarrenais/genética , Paraganglioma/genética , Epinefrina
17.
Int J Biol Macromol ; 253(Pt 8): 127561, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37865364

RESUMO

In the present study, carrageenan (CG) was combined with sodium alginate (SA), gum arabic (GA), and locust bean gum (LBG) to obtain four gum combinations (CG, CG + SA, CG + GA, and CG + LBG). The effects of different combinations on rheological properties and quiescent stabilities of PCEs were systematically investigated through characterization of fresh emulsion related parameters (rheological properties, forces between proteins, zeta potentials, surface tensions, interfacial adsorption properties, and multiple light scattering) and storage related parameters (visual appearance, creaming index, viscosities, particle sizes, and microscopic morphology). Rheological results indicated that CG PCEs had the highest apparent viscosities of 7.77-41.91 Pa·s at 0.01 s-1, followed by CG + SA PCEs (2.35-30.62 Pa·s), CG + GA PCEs (2.37-21.16 Pa·s), and CG + LBG PCEs (2.06-19.93 Pa·s). At low thickener concentration (0.02 %), CG PCE exhibited weak gel structure due to higher G' than G″ at all frequencies, while CG + SA, CG + GA, and CG + LBG PCEs had entangled network due to intersection between G' and G″. After three months of storage, CG + SA PCEs showed the lowest creaming index values (11.47-17.75 %), which were significantly lower than CG PCEs (15.35-20.85 %), CG + GA PCEs (15.97-24.42 %), and CG + LBG PCEs (17.13-21.71 %). Meanwhile, all the samples except for 0.02 % CG + SA PCE completely lost fluidity, and their viscosities were above 14,000 mPa·s. It was further found that CG stabilized emulsions showed severe droplet flocculation induced by hydrophobic interactions among adsorbed proteins. Combination of CG with SA, GA, and LBG, especially CG + SA, formed strong network structure and reduced contribution of hydrophobic interactions, which effectively inhibited flocculation of fat droplets, thereby improving rheological properties and storage stabilities of PCEs.


Assuntos
Alginatos , Goma Arábica , Goma Arábica/química , Carragenina , Alginatos/química , Emulsões/química , Gomas Vegetais/química , Reologia
18.
Polymers (Basel) ; 15(19)2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37835911

RESUMO

The purpose of this study is to analyze the reliability of predictive models for higher heating values related to organic materials. A theoretical model was developed, which utilizes bond dissociation energies (BDEs) to establish correlations between elemental composition and calorific values. Our analysis indicates that the energy contribution of one mole of hydrogen atoms is approximately equal to -144.4 kJ mol-1. Further investigation reveals significant variations in the bond dissociation energies of carbon atoms within organic compounds, resulting in a range of energy outputs from -414.30 to -275.34 kJ mol-1 per mole of carbon atoms. The presence of oxygen atoms in organic compounds has a negative impact on the magnitude of combustion heat, with values ranging from 131.1 to 207.17 kJ mol-1. The combustion mechanism imposes certain constraints, leading to the equation HHVg = -31.34·[C] - 144.44·[H] + 10.57·[O] for organic compounds. Based on the parameter sensitivity analysis, the coefficient associated with carbon mass fraction exhibits a significantly greater impact on result prediction accuracy, demonstrating a sensitivity value of 92.65%. The results of further analysis indicate that empirical correlations involving the mass fractions of the elements N and S in lignocellulosic materials may be prone to over-fitting, with sensitivity indices of 1.59% and 0.016%, respectively.

19.
Int Immunopharmacol ; 124(Pt B): 110970, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37748221

RESUMO

Rat Thy-1 nephritis (Thy-1N) is an experimental model for studying human mesangioproliferative glomerulonephritis (MsPGN), and its pathological features are glomerular mesangial cell (GMC) proliferation and extracellular matrix (ECM) accumulation. Although we have confirmed that renal lesions of Thy-1N rats are sublytic C5b-9-dependent, and ECM accumulation is related to tissue inhibitor of matrix metalloproteinase (TIMP) inhibiting matrix metalloproteinase (MMP) activity, whether sublytic C5b-9 can induce TIMP production by GMC in Thy-1N rat and the underlying mechanism remains unclear. In the study, we proved that the expressions of TIMP3, krϋppel-like transcription factor 5 (KLF5) and tumor necrosis factor receptor-associated factor 6 (TRAF6) were simultaneously up-regulated both in the renal tissues of Thy-1N rats (in vivo) and in the GMC exposed to sublytic C5b-9 (in vitro). Further mechanism exploration discovered that KLF5 and TRAF6 as two upstream molecules could induce TIMP3 gene transcription through binding to the same region i.e., -1801nt to -1554nt (GGGGAGGGGC) and -228nt to -46nt (GCCCCGCCCC) of TIMP3 promoter. In the process, TRAF6 mediated KLF5 K63-linked ubiquitination at K99 and K100 enhancing KLF5 nuclear localization and binding to TIMP3 promoter, augmenting its gene activation. Furthermore, the experiments in vivo exhibited that silencing KLF5, TRAF6 or TIMP3 gene could markedly lessen renal KLF5 K63-linked ubiquitination or TIMP3 induction, ECM accumulation and other pathological changes of Thy-1N rats. Besides, the positive expressions of above-mentioned these proteins and ECM accumulation and their correlation in the renal tissues of MsPGN patients were also demonstrated. Overall, our findings implicate that KLF5 and TRAF6 play a promoting role in sublytic C5b-9-triggered TIMP3 gene transcription and expression, which might provide a novel mechanistic insight into rat Thy-1N and human MsPGN.


Assuntos
Células Mesangiais , Nefrite , Humanos , Ratos , Animais , Células Mesangiais/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Nefrite/metabolismo , Ubiquitinação , Metaloproteinases da Matriz/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Inibidor Tecidual de Metaloproteinase-3/genética , Inibidor Tecidual de Metaloproteinase-3/metabolismo
20.
Langmuir ; 39(33): 11782-11787, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37562139

RESUMO

Tile-based DNA self-assembly is a cost-effective fabrication method for large-scale nanopatterns. Herein, we report a protocol to directly assemble DNA 2D arrays on silicon wafers and then use the DNA nanostructures as molds to fabricate the corresponding nanostructures on the silicon wafers by hydrogen fluoride (HF) etching. Similar HF etching has been used with robust large DNA origami structures as templates. This work demonstrates that DNA nanostructures assembled from small tiles are sufficiently stable for this process. The resulting feature size (∼8.6 nm) approaches the sizes of e-beam lithography. While the reported method is parallel and inexpensive, e-beam lithography is a serial method and is expensive. We expect that this method will be very useful for preparing fine nanopatterns in large areas.


Assuntos
Nanoestruturas , Silício , Silício/química , Porosidade , Nanoestruturas/química , DNA/química
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