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1.
APMIS ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644557

RESUMO

LncRNAs play an important role in autoimmune diseases. The purpose of this study was to explore the role of lncRNA SNHG1 in systemic lupus erythematosus (SLE), and laid a theoretical foundation for the study of SLE. The basic clinical information of all subjects was first collected for statistical analysis, and SNHG1 expression in the serum of all subjects was detected by RT-qPCR. The value of SNHG1 in the diagnosis of SLE was assessed by ROC. The correlation between SNHG1 and each blood sample index was analyzed by Pearson correlation analysis. The role of SNHG1 in primary peripheral blood mononuclear cells (PBMCs) apoptosis was explored. SNHG1 expression is relatively upregulated in patients with SLE compared to healthy people. SNHG1 expression was positively correlated with SLEDAI score, IgG, CRP, and ESR, and negatively correlated with C3 and C4. ROC indicated that SNHG1 has the potential to assist in the diagnosis of SLE. PBMCs apoptosis in SLE was higher than that in control group, the knockdown and overexpression of SNHG1 could correspondingly inhibit and promote PBMCs apoptosis. SNHG1 has the potential to be a diagnosis marker for SLE and may be involved in regulating PBMCs apoptosis.

2.
Lupus ; : 9612033241243175, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634475

RESUMO

AIM: This study aimed to investigate the expression of H19 and its possible molecular mechanism in systemic lupus erythematosus (SLE). METHODS: The expression of H19 and miR-19b in serum and peripheral blood mononuclear cells (PBMCs) were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Receiver operator characteristic (ROC) curve was constructed to evaluate the diagnostic value of serum H19 in SLE. Pearson correlation coefficient was used to analyze the correlation between serum levels of H19 and miR-19b. Flow cytometry and Cell counting kit-8 (CCK-8) assay were performed to detect cell apoptosis and viability. The levels of pro-inflammatory and anti-inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). Luciferase reporter gene assay was conducted to verify the interaction between H19 and miR-19b. RESULTS: The expression of H19 and miR-19b in SLE group were up-regulated and down-regulated, respectively. Serum H19 has certain clinical diagnostic value in SLE. In in vitro studies, overexpression of H19 can significantly inhibit the viability of PBMCs and promote apoptosis and inflammatory response of PBMCs by interacting with miR-19b. CONCLUSIONS: The expression of H19 is upregulated in patients with SLE and plays a role in cell function and inflammation by targeting miR-19b in PBMCs, which may be one of the pathological mechanisms of SLE.

3.
Nat Commun ; 15(1): 3185, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609368

RESUMO

Conventional liquid-phase methods lack precise control in synthesizing and processing materials with macroscopic sizes and atomic thicknesses. Water interfaces are ubiquitous and unique in catalyzing many chemical reactions. However, investigations on two-dimensional (2D) materials related to water interfaces remain limited. Here we report the growth of millimeter-sized 2D PbI2 single crystals at the water-air interface. The growth mechanism is based on an inherent ion-specific preference, i.e. iodine and lead ions tend to remain at the water-air interface and in bulk water, respectively. The spontaneous accumulation and in-plane arrangement within the 2D crystal of iodide ions at the water-air interface leads to the unique crystallization of PbI2 as well as other metal iodides. In particular, PbI2 crystals can be customized to specific thicknesses and further transformed into millimeter-sized mono- to few-layer perovskites. Additionally, we have developed water-based techniques, including water-soaking, spin-coating, water-etching, and water-flow-assisted transfer to recycle, thin, pattern, and position PbI2, and subsequently, perovskites. Our water-interface mediated synthesis and processing methods represents a significant advancement in achieving simple, cost-effective, and energy-efficient production of functional materials and their integrated devices.

4.
Clin Nucl Med ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38598734

RESUMO

ABSTRACT: A 56-year-old man with metastatic lung adenocarcinoma received combined 177Lu-FAP-2286 radiation therapy and targeted therapy. After 1 treatment cycle, improvement of symptoms and radiological remission was observed. Moreover, the patient did not report any adverse effects.

5.
Front Immunol ; 15: 1368322, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558821

RESUMO

Introduction: Activation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA. Methods: Dose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control. Results: The FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation. Discussion: The new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.


Assuntos
Glomerulonefrite por IGA , Lacticaseibacillus casei , Camundongos , Animais , Fator H do Complemento/genética , Camundongos Endogâmicos C57BL , Glomerulonefrite por IGA/patologia , Proteínas do Sistema Complemento/genética , Imunoglobulina A , Mutação
6.
Clin Nucl Med ; 49(5): 472-474, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38465996

RESUMO

ABSTRACT: A 57-year-old woman with a metastatic bone malignant solitary fibrous tumor received 177 Lu-FAP-2286 therapy. After 1 treatment cycle, 68 Ga-FAP-2286 PET/CT revealed remission of the lesions. Moreover, the patient did not report any adverse effects.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tumores Fibrosos Solitários , Feminino , Humanos , Pessoa de Meia-Idade , Radioisótopos , Radioisótopos de Gálio , Lutécio , Tumores Fibrosos Solitários/diagnóstico por imagem
7.
Bioresour Technol ; 399: 130575, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38479629

RESUMO

Aerobic kitchen waste composting can contribute to greenhouse gas (GHGs) emissions and global warming. This study investigated the effects of biochar and zeolite on GHGs emissions during composting. The findings demonstrated that biochar could reduce N2O and CH4 cumulative releases by 47.7 %and 47.9 %, respectively, and zeolite could reduce the cumulative release of CO2 by 28.4 %. Meanwhile, the biochar and zeolite addition could reduce the abundance of potential core microorganisms associated with GHGs emissions. In addition, biochar and zeolite reduced N2O emissions by regulating the abundance of nitrogen conversion functional genes. Biochar and zeolite were shown to reduce the impact of bacterial communities on GHGs emissions. In summary, this study revealed that biochar and zeolite can effectively reduce GHG emissions during composting by altering the compost microenvironment and regulating microbial community structure. Such findings are valuable for facilitating high-quality resource recovery of organic solid waste.


Assuntos
Compostagem , Gases de Efeito Estufa , Zeolitas , Gases de Efeito Estufa/análise , Zeolitas/química , Solo/química , Metano/análise , Carvão Vegetal , Nitrogênio/análise , Óxido Nitroso/análise
8.
Clin Nucl Med ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498615

RESUMO

PURPOSE: We aimed to evaluate the efficacy and safety of 225Ac-DOTATATE targeted α therapy (TAT) in various neuroendocrine neoplasms (NENs) with high somatostatin receptor (SSTR) expression. PATIENTS AND METHODS: This single-center prospective study included 10 patients with histologically diagnosed NENs that exhibited increased SSTR expression on 68Ga-DOTATATE PET/CT imaging. All patients received 225Ac-DOTATATE TAT. The primary end points were molecular imaging-based response and disease control rate (DCR), measured using the slightly modified Positron Emission Tomography Response Criteria in Solid Tumors 1.0. The secondary end points were adverse event profiles and clinical responses. The adverse event profile was determined according to the Common Terminology Criteria for Adverse Events version 5.0. Clinical response was assessed using the EORTC QLQ-C30 v3.0 (European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire version 3.0). RESULTS: A molecular imaging-based partial response was observed in 40% of all patients, SD in 40%, PD in 20%, and DCR in 80%. The DCR was 83.3% (5/6) in patients who were previously treated with 177Lu-DOTATATE. According to the EORTC QLQ-C30 v3.0 score, most symptoms improved after 225Ac-DOTATATE treatment, with only diarrhea showing no improvement. Grade III/IV hematological, kidney, and liver toxicities were not observed. The median follow-up time was 14 months (7-22 months), and no deaths were reported. CONCLUSIONS: This initial study suggests that 225Ac-DOTATATE is a potentially promising option for treating NENs with elevated SSTR expression, with an acceptable toxicity profile and well-tolerated adverse effects.

9.
Radiol Med ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512625

RESUMO

PURPOSE: Breast cancer's impact necessitates refined diagnostic approaches. This study develops a nomogram using radiology quantitative features from contrast-enhanced cone-beam breast CT for accurate preoperative classification of benign and malignant breast tumors. MATERIAL AND METHODS: A retrospective study enrolled 234 females with breast tumors, split into training and test sets. Contrast-enhanced cone-beam breast CT-images were acquired using Koning Breast CT-1000. Quantitative assessment features were extracted via 3D-slicer software, identifying independent predictors. The nomogram was constructed to preoperative differentiation benign and malignant breast tumors. Calibration curve was used to assess whether the model showed favorable correspondence with pathological confirmation. Decision curve analysis confirmed the model's superiority. RESULTS: The study enrolled 234 female patients with a mean age of 50.2 years (SD ± 9.2). The training set had 164 patients (89 benign, 75 malignant), and the test set had 70 patients (29 benign, 41 malignant). The nomogram achieved excellent predictive performance in distinguishing benign and malignant breast lesions with an AUC of 0.940 (95% CI 0.900-0.940) in the training set and 0.970 (95% CI 0.940-0.970) in the test set. CONCLUSION: This study illustrates the effectiveness of quantitative radiology features derived from contrast-enhanced cone-beam breast CT in distinguishing between benign and malignant breast tumors. Incorporating these features into a nomogram-based diagnostic model allows for breast tumor diagnoses that are objective and possess good accuracy. The application of these insights could substantially increase reliability and efficacy in the management of breast tumors, offering enhanced diagnostic capability.

10.
Aging (Albany NY) ; 16(4): 4014-4032, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38393698

RESUMO

BACKGROUND: Breast cancer (BC) is a heterogeneous tumor with a variety of etiology and clinical features. Antibody-dependent cell phagocytosis (ADCP) is the last step of immune checkpoint inhibition (ICI), and macrophages detect and recognize tumor cells, then destroy and engulf tumor cells. Despite the large number, negative regulators that inhibit phagocytic activity are still a key obstacle to the full efficacy of ICI. PATIENTS AND METHODS: An ADCP-related risk score prognostic model for risk stratification as well as prognosis prediction was established in the Cancer Genome Atlas (TCGA) cohort. The predictive value of ADCP risk score in prognosis and immunotherapy was also further validated in the TCGA along with International Cancer Genome Consortium cohorts. To promote the clinical application of the risk score, a nomogram was established, with its effectiveness verified by different methods. RESULTS: In this study, the genes collected from previous studies were defined as ADCP-related genes. In BC patients, two ADCP-related subtypes were identified. The immune characteristics and prognostic stratification were significant different between them. CONCLUSIONS: We identified two subtypes associated with ADCP gene expression in breast cancer. They have significant differences in immune cells, molecular functions, HLA family genes, immune scores, stromal scores, and inflammatory gene expression, which have important guiding significance for the selection of clinical treatment methods. At the same time, we constructed a risk model based on ADCP, and the risk score can be used as a good indicator of prognosis, providing potential therapeutic advantages for chemotherapy and immunotherapy, thus helping the clinical decision-making of BC patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Citofagocitose , Prognóstico , Anticorpos , Nomogramas , Microambiente Tumoral
11.
World J Clin Cases ; 12(2): 405-411, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38313643

RESUMO

BACKGROUND: Small cell lung cancer (SCLC) is a common and aggressive subtype of lung cancer. It is characterized by rapid growth and a high mortality rate. Approximately 10% of patients with SCLC present with brain metastases at the time of diagnosis, which is associated with a median survival of 5 mo. This study aimed to summarize the effect of bevacizumab on the progression-free survival (PFS) and overall survival of patients with brain metastasis of SCLC. CASE SUMMARY: A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks. The patient was diagnosed with limited-stage SCLC. He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo. CONCLUSION: The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

12.
Addict Biol ; 29(2): e13375, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38380802

RESUMO

Recent studies found that non-coding RNAs (ncRNAs) played crucial roles in drug addiction through epigenetic regulation of gene expression and underlying drug-induced neuroadaptations. In this study, we characterized lncRNA transcriptome profiles in the nucleus accumbens (NAc) of mice exhibiting morphine-conditioned place preference (CPP) and explored the prospective roles of novel differentially expressed lncRNA, lncLingo2 and its derived miR-876-5p in the acquisition of opioids-associated behaviours. We found that the lncLingo2 was downregulated within the NAc core (NAcC) but not in the NAc shell (NAcS). This downregulation was found to be associated with the development of morphine CPP and heroin intravenous self-administration (IVSA). As Mfold software revealed that the secondary structures of lncLingo2 contained the sequence of pre-miR-876, transfection of LV-lncLingo2 into HEK293 cells significantly upregulated miR-876 expression and the changes of mature miR-876 are positively correlated with lncLingo2 expression in NAcC of morphine CPP trained mice. Delivering miR-876-5p mimics into NAcC also inhibited the acquisition of morphine CPP. Furthermore, bioinformatics analysis and dual-luciferase assay confirmed that miR-876-5p binds to its target gene, Kcnn3, selectively and regulates morphine CPP training-induced alteration of Kcnn3 expression. Lastly, the electrophysiological analysis indicated that the currents of small conductance calcium-activated potassium (SK) channel was increased, which led to low neuronal excitability in NAcC after CPP training, and these changes were reversed by lncLingo2 overexpression. Collectively, lncLingo2 may function as a precursor of miR-876-5p in NAcC, hence modulating the development of opioid-associated behaviours in mice, which may serve as an underlying biomarker and therapeutic target of opioid addiction.


Assuntos
MicroRNAs , RNA Longo não Codificante , Humanos , Camundongos , Animais , Analgésicos Opioides/farmacologia , Analgésicos Opioides/metabolismo , Epigênese Genética , Células HEK293 , Morfina/farmacologia , Morfina/metabolismo , Núcleo Accumbens/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo
13.
ACS Appl Mater Interfaces ; 16(9): 11704-11714, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38406990

RESUMO

The microscale flow preparation scheme has been widely used in the preparation of inorganic perovskite nanocrystals (NCs). It is considered to be the most promising method for large-scale production. Recently, it has been suggested that increasing the precursor concentration can further improve efficiency, but there is still a lack of understanding of high-concentration synthesis. Here, we develop a microscale flow synthesis scheme using high-concentration precursors, and the typical concentration value in the reaction phase reaches 0.035 mol/L using cesium acetate. The CsPbBr3 NCs with sharp photoluminescence (PL) at 515.7 nm can be obtained, and their PL quantum yield after post-treatment exceeds 90%. The effect of the molar ratio of Pb/Cs (Rm), reaction time, reaction temperature, and excess ligands on this flow reaction is studied. Several new phenomena are observed in our experiment. At 120 °C, some Cs4PbBr6 NCs exist in addition to the usual CsPbBr3 nanoplatelets. Excess ligands lead to the formation of numerous Cs4PbBr6 NCs with a bright green PL, and these NCs will spontaneously transform into a nonemission form in the film. Moreover, mixed-halide CsPbBrxI3-x NCs and CsPbI3 NCs are also prepared in this scheme, and then they are used to obtain LEDs in a range of colors.

14.
BMC Nephrol ; 25(1): 47, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38311719

RESUMO

BACKGROUND: Chronic inflammation, reflected by an increased blood C-reactive protein (CRP) level, is common in patients with chronic kidney disease (CKD) and is involved in the development of renal anemia. This systematic review aims to investigate the impacts of CRP on the efficacy of hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) in the treatment of renal anemia in patients with CKD. METHODS: We conducted a comprehensive search of electronic databases including Pubmed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, and the International Clinical Trials Registry Platform (ICTRP), from their inception to May 19, 2022. We systematically reviewed evidence from randomized controlled trials using HIF-PHIs for renal anemia treatment. The mean difference (MD) in changes in hemoglobin concentration (∆Hb) before and after treatment served as the meta-analysis outcome, utilizing a random-effects model. We compared groups with CRP levels greater than or equal to the upper limit of normal (ULN) and less than the ULN. Additionally, further analysis was conducted in the CRP ≥ ULN group comparing HIF-PHIs and erythropoiesis-stimulating agents (ESA). RESULTS: A total of 7 studies from 6 publications were included in the analysis. In the comparison between the CRP ≥ ULN group and the CRP < ULN group, 524 patients from 4 studies were incorporated into the analysis. All patients received roxadustat as the primary intervention. The pooled results revealed no significant difference in ΔHb between patients with CRP ≥ ULN and CRP < ULN at baseline (Mean Difference: 0.00, 95% Confidence Interval: -0.32 to 0.33, P = 0.99). Moreover, within the CRP ≥ ULN group, three studies involving 1399 patients compared the efficacy of roxadustat and erythropoiesis-stimulating agents (ESAs). The results indicated no significant difference in ΔHb between patients treated with ESAs and HIF-PHIs (Mean Difference: 0.24, 95% Confidence Interval: -0.08 to 0.56, P = 0.14). In terms of medication dosage, an increase in ESA dose over time was observed across various studies, particularly evident in the CRP ≥ ULN group, while the dose of roxadustat remains constant over time and is not influenced by the baseline levels of CRP. CONCLUSIONS: Our systematic review demonstrates that roxadustat exhibits similar efficacy across different CRP levels. Moreover, within the CRP ≥ ULN group, roxadustat can maintain efficacy comparable to ESA without the necessity for dose escalation. TRIAL REGISTRATION: CRD42023396704.


Assuntos
Anemia , Hematínicos , Isoquinolinas , Insuficiência Renal Crônica , Humanos , Anemia/tratamento farmacológico , Anemia/etiologia , Proteína C-Reativa , Doença Crônica , Glicina/análogos & derivados , Hematínicos/uso terapêutico , Isoquinolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico
15.
Pharm Res ; 41(3): 531-546, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38366235

RESUMO

PURPOSE: Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide. METHODS: Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 µL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses. RESULTS: In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards. IN CONCLUSION: The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma.


Assuntos
Lentes de Contato , Glaucoma , Poliésteres , Polietilenoglicóis , Sulfonamidas , Tiazinas , Humanos , Timolol/farmacocinética , Timolol/uso terapêutico , Micelas , Anti-Hipertensivos/farmacocinética , Glaucoma/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Soluções Oftálmicas/uso terapêutico
16.
Biomolecules ; 14(2)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38397460

RESUMO

MicroRNAs (miRNAs) in oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) play a pivotal role in modulating intercellular communications between tumor cells and other cells in the microenvironment, thereby influencing tumor progression and the efficacy of therapeutic interventions. However, a comprehensive inventory of these secretory miRNAs in sEVs and their biological and clinical implications remains elusive. This study aims to profile the miRNA content of OSCC cell line sEVs and computationally elucidate their biological and clinical relevance. We conducted miRNA sequencing to compare the miRNA profiles of OSCC cells and their corresponding sEVs. Our motif enrichment analysis identified specific sorting motifs that are implicated in either cellular retention or preferential sEV secretion. Target cell analysis suggested that the sEV miRNAs potentially interact with various immune cell types, including natural killer cells and dendritic cells. Additionally, we explored the clinical relevance of these miRNAs by correlating their expression levels with TNM stages and patient survival outcomes. Intriguingly, our findings revealed that a distinct sEV miRNA signature is associated with lymph node metastasis and poorer survival in patients in TCGA-HNSC dataset. Collectively, this research furthers our understanding of the miRNA sorting mechanisms in OSCC and underscores their clinical implications.


Assuntos
Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Metástase Linfática , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Linhagem Celular Tumoral , Vesículas Extracelulares/metabolismo , Microambiente Tumoral
17.
Molecules ; 29(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38398602

RESUMO

The use of gaseous CO in Pd-catalyzed carbonylative quinolone synthesis presents challenges related to safety and precise pressure control. In response, a streamlined non-gaseous synthesis of 4-quinolone compounds has been developed. This study introduces a tunable CO-releasing system utilizing Fe(CO)5 activated by a dual-base system of piperazine and triethylamine. This alternative liquid CO resource facilitates the palladium-catalyzed carbonylative C-C coupling and subsequent intramolecular cyclization. By tuning the tandem kinetics of carbonylation and cyclization, this non-gaseous method achieves the successful synthesis of 22 distinct 4-quinolones with excellent yields. This is achieved through the three-component condensation of sub-stoichiometric amounts of Fe(CO)5 with 2-iodoaniline and terminal alkynes. Operando mechanistic studies have revealed a novel CO transfer mechanism that facilitates homogeneous carbonylative cyclization, distinguishing this method from traditional techniques. In addition to addressing safety concerns, this approach also provides precise control over selectivity, with significant implications for pharmaceutical research and the efficient synthesis of pharmaceutical and bioactive compounds.

18.
AAPS PharmSciTech ; 25(2): 35, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332223

RESUMO

Currently, the marketed ophthalmic preparations of pranoprofen (PF) are mainly eye drops, but due to the special clearance mechanism of the eye and corneal reflex, the contact time between the drug and the focal site is short, most of the drug is lost, and the bioavailability is less than 5%. In the present study, an in situ gel eye drop containing no bacteriostatic agent and sensitive to temperature and ions was designed for delivery of PF. It was demonstrated to meet the criteria for ophthalmic preparations by characterization such as appearance content sterility. Ocular irritation tests showed a favorable safety profile. In vivo ocular retention time experiments showed that the ocular retention time of the pranoprofen gel was 4.41 times longer than that of commercially available drops (Pranopulin®), and the nasal tear excretion of the pranoprofen gel was lower than that of Pranopulin®, which suggests that the drug loss was reduced relative to that of the drops. The efficacy of the pranoprofen gel against tincture of cayenne pepper-induced corneal and conjunctival inflammation was examined using Pranopulin® as a control and in conjunction with inflammation scores, H&E slice results, and levels of IL-1ß, IL-6, and TNF-α. The results showed that pranoprofen gel and Pranololin® had significant efficacy in the treatment of corneal and conjunctival inflammation, and the anti-inflammatory effect of pranoprofen gel was superior to that of Pranololin®. This study provides a new option for the treatment of corneal and conjunctival inflammation.


Assuntos
Benzopiranos , Córnea , Propionatos , Humanos , Preparações de Ação Retardada/farmacologia , Inflamação/tratamento farmacológico , Soluções Oftálmicas
19.
Food Funct ; 15(3): 1598-1611, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38240388

RESUMO

Psychobiotics that modulate the gut-brain axis have emerged as promising interventions for clinical mental disorders. Bifidobacterium breve CCFM1025 has demonstrated antidepressant effects in both mice and patients with major depression. Nevertheless, the precise mechanism of action of CCFM1025 in emotional regulation remains ambiguous. This study aimed to explore the colonization capacity of CCFM1025 and its dose-dependent effect on emotional regulation in mice exposed to chronic unpredictable mild stress (CUMS). Additionally, we examined its regulatory effects on intestinal and serum metabolites in mice. The results revealed that CCFM1025 did not exhibit a heightened gut retention capability compared to the conspecific control strain. Nevertheless, CCFM1025 exhibited dose-dependent mitigation of anxiety-like behavior and memory impairment induced by CUMS, while also restoring gut microbiota homeostasis. Notably, CCFM1025 demonstrated a robust ability to exert potent gut metabolite regulation, resulting in significant elevation of bile acid and tryptophan metabolites in the gut contents and serum of mice. These findings indicate that the impact of CCFM1025 on emotional regulation may be attributed to its regulation of gut metabolites rather than its gut retention capability. The potential of Bifidobacterium to modulate bile acid metabolism may serve as a valuable avenue for regulating the gut microbiota and successfully exert emotion regulation.


Assuntos
Bifidobacterium breve , Transtorno Depressivo Maior , Regulação Emocional , Humanos , Camundongos , Animais , Bifidobacterium breve/metabolismo , Bifidobacterium , Estresse Psicológico/metabolismo , Ácidos e Sais Biliares/metabolismo , Depressão/metabolismo
20.
Pharmacol Res ; 200: 107062, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38211637

RESUMO

Extracellular vesicles (EVs) are tiny lipid bilayer-enclosed membrane particles released from a variety of cell types into the surrounding environment. These EVs have massive participated in cell-to-cell communication and interspecies communication. In recent years, plant-derived extracellular vesicles (PDEVs) and "exosome-like" EVs populations found in distinct plants have attracted widespread attention. Especially, research on medicinal plant-derived extracellular vesicles (MPDEVs) are increasing, which are considered a kind of promising natural compound. This review summarizes current knowledge on MPDEVs in terms of bioactive compounds, including small RNA, protein, lipid, and metabolite, have been found on the surface and/or in the lumen of MPDEVs. Moreover, both in vitro and in vivo experiments have shown that MPDEVs exert broad biomedical functions, such as anti-inflammatory, anticancer, antioxidant, modulate microbiota, etc. MPDEVs may be a better substitute than animal-derived extracellular vesicles (ADEVs) because of safety and biocompatibility in the future.


Assuntos
Exossomos , Vesículas Extracelulares , Plantas Medicinais , Animais , Vesículas Extracelulares/metabolismo , Exossomos/metabolismo , Comunicação Celular , RNA/metabolismo
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