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1.
World J Gastrointest Oncol ; 16(4): 1344-1360, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660669

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant cancer, characterized by frequent mucin overexpression. MUC1 has been identified as a critical oncogene in the progression of CCA. However, the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still incomplete. AIM: To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA patients. METHODS: Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins, complemented by bioinformatic analyses. Subsequent validations were conducted through spatial transcriptomics and immunohistochemistry. The construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm, which was further confirmed by independent cohorts and diverse data types. RESULTS: CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased invasiveness. MUC5AC-high cells were found to promote CCA progression through WNT signaling. MUC5B-high cells exhibited robust cellular oxidation activities, leading to resistance against antitumoral treatments. MUC13-high cells were observed to secret chemokines, recruiting and transforming macrophages into the M2-polarized state, thereby suppressing antitumor immunity. MUC16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with neutrophils. Utilizing the expression levels of these mucins, a risk factor evaluation formula for CCA was developed and validated across multiple cohorts. CCA samples with higher risk factors exhibited stronger metastatic potential, chemotherapy resistance, and poorer prognosis. CONCLUSION: Our study elucidates the functional mechanisms through which mucins contribute to CCA development, and provides tools for risk stratification in CCA.

2.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1641-1660, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621949

RESUMO

This study explored the existence forms(original constituents and metabolites) of Tiantian Capsules, Aloe, and Tiantian Capsules without Aloe in rats for the first time, aiming to clarify the contribution of Aloe to the existence form of Tiantian Capsules. Rats were administrated with corresponding drugs by gavage once a day for seven consecutive days. All urine and feces samples were collected during the seven days of administration, and blood samples were collected 0.5, 1, and 1.5 h after the last administration. UHPLC-Q-TOF-MS was employed to detect and identify the original constituents and metabolites in the samples. A total of 34, 28, and 2 original constituents and 64, 94, and 0 metabolites were identified in the samples of rats administrated with Aloe, Tiantian Capsules, and Tiantian Capsules without Aloe, respectively. The main metabolic reactions were methylation, hydrogenation, hydroxylation, dehydroxylation, glucuronidation, and sulfation. This study clarified for the first time the existence forms and partial metabolic pathways of Aloe, Tiantian Capsules, and Tiantian Capsules without Aloe in rats, laying a foundation for revealing their effective forms. The findings are of great significance to the research on the functioning mechanism and quality control of Aloe and Tiantian Capsules.


Assuntos
Aloe , Medicamentos de Ervas Chinesas , Ratos , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/metabolismo , Administração Oral , Fezes , Cápsulas
3.
Clin Lab ; 70(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38623677

RESUMO

BACKGROUND: The goal was to explore the aberrant human epididymal protein 4 (HE4) in chronic heart failure (CHF) patients and its association with C-reactive protein (CRP), uric acid (UA), and homocysteine (HCY). METHODS: Analysis of serum HE4 and its relevance with associated indexes in 117 CHF patients was implemented. RESULTS: Serum HE4 in CHF patients was linked with the disease's severity and CRP, UA, and HCY. An assessment value was provided for it (p < 0.05). CONCLUSIONS: HE4 is aberrant in CHF patients' serum and is associated with the disease's severity and CRP, UA, and HCY's indexes.


Assuntos
Proteína C-Reativa , Insuficiência Cardíaca , Humanos , Ácido Úrico , Homocisteína , Insuficiência Cardíaca/diagnóstico , Doença Crônica
4.
Talanta ; 274: 126004, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38564824

RESUMO

Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) serve as vital mediators essential for preserving intracellular redox homeostasis within the human body, thereby possessing significant implications across physiological and pathological domains. Nevertheless, deviations from normal levels of ROS, RNS, and RSS disturb redox homeostasis, leading to detrimental consequences that compromise bodily integrity. This disruption is closely linked to the onset of various human diseases, thereby posing a substantial threat to human health and survival. Small-molecule fluorescent probes exhibit considerable potential as analytical instruments for the monitoring of ROS, RNS, and RSS due to their exceptional sensitivity and selectivity, operational simplicity, non-invasiveness, localization capabilities, and ability to facilitate in situ optical signal generation for real-time dynamic analyte monitoring. Due to their distinctive transition from their spirocyclic form (non-fluorescent) to their ring-opened form (fluorescent), along with their exceptional light stability, broad wavelength range, high fluorescence quantum yield, and high extinction coefficient, rhodamine fluorophores have been extensively employed in the development of fluorescent probes. This review primarily concentrates on the investigation of fluorescent probes utilizing rhodamine dyes for ROS, RNS, and RSS detection from the perspective of different response groups since 2016. The scope of this review encompasses the design of probe structures, elucidation of response mechanisms, and exploration of biological applications.

5.
Sci Adv ; 10(14): eadl1884, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579002

RESUMO

Introducing natural Bouligand structure into synthetics is expected to develop high-performance structural materials. Interfibrous interface is critical to load transfer, and mechanical functionality of bioinspired Bouligand structure yet receives little attention. Here, we propose one kind of hierarchical and reconfigurable interfibrous interface based on moderate orderliness to mechanically reinforce bioinspired Bouligand structure. The interface imparted by moderate alignment of adaptable networked nanofibers hierarchically includes nanofiber interlocking and hydrogen-bonding (HB) network bridging, being expected to facilitate load transfer and structural stability through dynamic adjustment in terms of nanofiber sliding and HB breaking-reforming. As one demonstration, the hierarchical and reconfigurable interfibrous interface is constructed based on moderate alignment of networked bacterial cellulose nanofibers. We show that the resultant bioinspired Bouligand structural material exhibits unusual strengthening and toughening mechanisms dominated by interface-microstructure multiscale coupling. The proposed interfibrous interface enabled by moderate orderliness would provide mechanical insight into the assembly of widely existing networked nanofiber building blocks toward high-performance macroscopic bioinspired structural assemblies.

6.
J Mol Neurosci ; 74(2): 48, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662286

RESUMO

We aimed to develop and validate a predictive model for identifying long-term survivors (LTS) among glioblastoma (GB) patients, defined as those with an overall survival (OS) of more than 3 years. A total of 293 GB patients from CGGA and 169 from TCGA database were assigned to training and validation cohort, respectively. The differences in expression of immune checkpoint genes (ICGs) and immune infiltration landscape were compared between LTS and short time survivor (STS) (OS<1.5 years). The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify the genes differentially expressed between LTS and STS. Three different machine learning algorithms were employed to select the predictive genes from the overlapping region of DEGs and WGCNA to construct the nomogram. The comparison between LTS and STS revealed that STS exhibited an immune-resistant status, with higher expression of ICGs (P<0.05) and greater infiltration of immune suppression cells compared to LTS (P<0.05). Four genes, namely, OSMR, FMOD, CXCL14, and TIMP1, were identified and incorporated into the nomogram, which possessed good potential in predicting LTS probability among GB patients both in the training (C-index, 0.791; 0.772-0.817) and validation cohort (C-index, 0.770; 0.751-0.806). STS was found to be more likely to exhibit an immune-cold phenotype. The identified predictive genes were used to construct the nomogram with potential to identify LTS among GB patients.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Aprendizado de Máquina , Humanos , Glioblastoma/genética , Glioblastoma/imunologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Sobreviventes de Câncer , Algoritmos , Nomogramas , Masculino , Feminino , Transcriptoma , Pessoa de Meia-Idade
7.
Ying Yong Sheng Tai Xue Bao ; 35(3): 847-857, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38646773

RESUMO

Crop health directly affects yields and food security. At present, agrochemicals such as fertilizers and pesticides are mainly used in agricultural production to promote crop health. However, long-term excessive utilization of agrochemicals will damage the ecological environment of farmlands and increase the safety risk of agricultural products. It is urgent to explore efficient and environment-friendly agricultural products. Rhizosphere microbiome are considered as the second genome of plants, which are closely related to crop health. Understanding the key functional microbes, microbe-microbe interactions, and plant-microbe interactions are fundamental for exploring the potential of beneficial microbes in promoting crop health. However, due to the heterogeneity and complexity of the natural environment, stimulating the function of indigenous microorganisms remains uncertain. Synthetic microbial community (SynCom) is an artificial combination of two or more different strain isolates of microorganisms, with different taxonomic, genetic, or functional characteristic. Because of the advantages of maintaining species diversity and community stability, SynCom has been widely applied in the fields of human health, environmental governance and industrial production, and may also have great potential in promoting crop health. We summarized the concept and research status of SynCom, expounded the principles and methods of constructing SynCom, and analyzed the research on the promotion of crop health by exploring the mechanism of plant-microbe interactions, promoting plant growth and development, and improving stress resistance. Finally, we envisaged the future prospects to guide the using SynCom to improve crop health.


Assuntos
Produtos Agrícolas , Microbiota , Rizosfera , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/microbiologia , Microbiologia do Solo , Biologia Sintética/métodos , Agricultura/métodos
8.
Adv Sci (Weinh) ; : e2401194, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647250

RESUMO

Tuning the thermal transport properties of hybrid halide perovskites is critical for their applications in optoelectronics, thermoelectrics, and photovoltaics. Here, an effective strategy is demonstrated to modulate the thermal transport property of hybrid perovskites by halide alloying. A highly tunable thermal conductivity of mixed-halide hybrid perovskites is achieved due to halide-alloying and structural distortion. The experimental measurements show that the room temperature thermal conductivity of MAPb(BrxI1- x)3 (x = 0─1) can be largely modulated from 0.27 ± 0.07 W m-1 K-1 (x = 0.5) to 0.47 ± 0.09 W m-1 K-1 (x = 1). Molecular dynamics simulations further demonstrate that the thermal conductivity reduction of hybrid halide perovskites results from the suppression of the mean free paths of the low-frequency acoustic and optical phonons. It is found that halide alloying and the induced structural distortion can largely increase the scatterings of optical and acoustic phonons, respectively. The confined diffusion of MA+ cations in the octahedra cage is found to act as an additional thermal transport channel in hybrid perovskites and can contribute around 10-20% of the total thermal conductivity. The findings provide a strategy for tailoring the thermal transport in hybrid halide perovskites, which may largely benefit their related applications.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38614958

RESUMO

BACKGROUND AND HYPOTHESIS: Activation of NF-κB-signalling is key in the pathogenesis of chronic kidney diseases (CKD). However, a certain level of NF-κB activity is necessary to enable tissue repair. METHODS: To investigate the relationship between activated and inactivated NF-κB signaling on the pathogenesis of CKD using mouse models of NF-κB partial inactivation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into alanine) and activation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into serine). RESULTS: The density of CD3, CD8, CD68 positive cells, as well as the expression of IL-6, TRAF-1, and NAF-1 in the kidney tissues of NF-κBC59A mice were reduced, whereas an opposing pattern was observed in the NF-κBC59S mice. Blood pressure, kidney fibrosis (analyzed by PAS-, Masson trichrome-, and Sirius-Red-staining as well as α-SMA immunofluorescence), serum creatinine and urinary albumin-to-creatinine-ratio are markedly increased in NF-κB activated and inactivated mice compared to controls. Transmission electron microscopy indicated that the glomerular basement membrane was thicker in both NF-κBC59A and NF-κBC59S mice compared to wild-type mice. CONCLUSIONS: Using mice models with partially activated and inactivated NF-κB pathways suggests that there is an apparently U-shaped relationship between blood pressure, kidney function as well as morphology and the activation of the NF-κB pathway. A certain optimal activity of the NF-κB pathway seems to be important to maintain optimal kidney function and morphology.

10.
Quant Imaging Med Surg ; 14(4): 2993-3005, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617165

RESUMO

Background: It is crucial to distinguish unstable from stable intracranial aneurysms (IAs) as early as possible to derive optimal clinical decision-making for further treatment or follow-up. The aim of this study was to investigate the value of a deep learning model (DLM) in identifying unstable IAs from computed tomography angiography (CTA) images and to compare its discriminatory ability with that of a conventional logistic regression model (LRM). Methods: From August 2011 to May 2021, a total of 1,049 patients with 681 unstable IAs and 556 stable IAs were retrospectively analyzed. IAs were randomly divided into training (64%), internal validation (16%), and test sets (20%). Convolutional neural network (CNN) analysis and conventional logistic regression (LR) were used to predict which IAs were unstable. The area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the discriminating ability of the models. One hundred and ninety-seven patients with 229 IAs from Banan Hospital were used for external validation sets. Results: The conventional LRM showed 11 unstable risk factors, including clinical and IA characteristics. The LRM had an AUC of 0.963 [95% confidence interval (CI): 0.941-0.986], a sensitivity, specificity and accuracy on the external validation set of 0.922, 0.906, and 0.913, respectively, in predicting unstable IAs. In predicting unstable IAs, the DLM had an AUC of 0.771 (95% CI: 0.582-0.960), a sensitivity, specificity and accuracy on the external validation set of 0.694, 0.929, and 0.782, respectively. Conclusions: The CNN-based DLM applied to CTA images did not outperform the conventional LRM in predicting unstable IAs. The patient clinical and IA morphological parameters remain critical factors for ensuring IA stability. Further studies are needed to enhance the diagnostic accuracy.

11.
BMC Microbiol ; 24(1): 123, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622504

RESUMO

BACKGROUND: Rhizosphere microorganisms are vital in plants' growth and development and these beneficial microbes are recruited to the root-zone soil when experiencing various environmental stresses. However, the effect of white grub (Maladera verticalis) larvae feeding on the structure and function of rhizosphere microbial communities of aerobic rice (Oryza sativa L.) is unclear. RESULTS: In this study, we compared physicochemical properties, enzyme activities, and microbial communities using 18 samples under healthy and M. verticalis larvae-feeding aerobic rice rhizosphere soils at the Yunnan of China. 16 S rRNA and ITS amplicons were sequenced using Illumina high throughput sequencing. M. verticalis larvae feeding on aerobic rice can influence rhizosphere soil physicochemical properties and enzyme activities, which also change rhizosphere microbial communities. The healthy and M. verticalis larvae-feeding aerobic rice rhizosphere soil microorganisms had distinct genus signatures, such as possible_genus_04 and Knoellia genera in healthy aerobic rice rhizosphere soils and norank_f__SC - I-84 and norank_f__Roseiflexaceae genera in M. verticalis larvae-feeding aerobic rice rhizosphere soils. The pathway of the metabolism of terpenoids and polyketides and carbohydrate metabolism in rhizosphere bacteria were significantly decreased after M. verticalis larvae feeding. Fungal parasite-wood saprotroph and fungal parasites were significantly decreased after M. verticalis larvae feeding, and plant pathogen-wood saprotroph and animal pathogen-undefined saprotroph were increased after larvae feeding. Additionally, the relative abundance of Bradyrhizobium and Talaromyces genera gradually increased with the elevation of the larvae density. Bacterial and fungal communities significantly correlated with soil physicochemical properties and enzyme activities, respectively. CONCLUSIONS: Based on the results we provide new insight for understanding the adaptation of aerobic rice to M. verticalis larvae feeding via regulating the rhizosphere environment, which would allow us to facilitate translation to more effective measures.


Assuntos
Oryza , Animais , Oryza/microbiologia , Larva , Rizosfera , China , Bactérias , Solo/química , Microbiologia do Solo
12.
Nat Commun ; 15(1): 3299, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632245

RESUMO

Improving the absorption of electromagnetic waves at low-frequency bands (2-8 GHz) is crucial for the increasing electromagnetic (EM) pollution brought about by the innovation of the fifth generation (5G) communication technology. However, the poor impedance matching and intrinsic attenuation of material in low-frequency bands hinders the development of low-frequency electromagnetic wave absorbing (EMWA) materials. Here we propose an interface-induced dual-pinning mechanism and establish a magnetoelectric bias interface by constructing bilayer core-shell structures of NiFe2O4 (NFO)@BiFeO3 (BFO)@polypyrrole (PPy). Such heterogeneous interface could induce distinct magnetic pinning of the magnetic moment in the ferromagnetic NFO and dielectric pinning of the dipole rotation in PPy. The establishment of the dual-pinning effect resulted in optimized impedance and enhanced attenuation at low-frequency bands, leading to better EMWA performance. The minimum reflection loss (RLmin) at thickness of 4.43 mm reaches -65.30 dB (the optimal absorption efficiency of 99.99997%), and the effective absorption bandwidth (EAB) can almost cover C-band (4.72 ~ 7.04 GHz) with low filling of 15.0 wt.%. This work proposes a mechanism to optimize low-frequency impedance matching with electromagnetic wave (EMW) loss and pave an avenue for the research of high-performance low-frequency absorbers.

13.
Sci Rep ; 14(1): 8324, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594513

RESUMO

Bladder cancer (BLCA) is a common malignant tumor in urinary system all over the world. However, due to its high recurrence rate and complex causes, clinicians often have limited options for surgical and drug treatments. Recent researchs on the molecular mechanism of BLCA have reveals its biological progress and potential for early diagnosis. Serine hydroxymethyltransferase 1/2 (SHMT1/2) is a crucial enzyme in the one-carbon metabolism of tumor cells, and the expression levels of these isozymes have been found to be associated with the biological progression of various malignant tumors. However, the impact of SHMT1/2 on the biological progression of bladder cancer and its molecular regulation mechanism remain unclear. In this research utilizes BLCA clinical sample data, the TCGA database, and in vitro cell experiments to predict the expression levels of SHMT1/2 in BLCA. The findings indicate that SHMT1 remained unchanged, while SHMT2 expression is increased in BLCA, which was related to poor prognosis. Additionally, SHMT2 affects the growth, migration, and apoptosis of bladder cancer cells in vitro. It also influences the expression levels of E-cadherin and N-cadherin, ultimately impacting the malignant biological progression of bladder tumors. These results establish a correlation between SHMT2 and the malignant biological progression of BLCA, providing a theoretical basis for the early diagnosis and treatment of bladder cancer.


Assuntos
Glicina Hidroximetiltransferase , Neoplasias da Bexiga Urinária , Humanos , Glicina Hidroximetiltransferase/genética , Neoplasias da Bexiga Urinária/metabolismo , Serina/metabolismo , Prognóstico
15.
Int J Endocrinol ; 2024: 8414689, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590929

RESUMO

Objective: The growing evidence shows that parathyroid hormone (PTH) may affect glucose metabolism. However, the relationship between them is still controversial among diabetic patients. The current study aimed to investigate the relationship between PTH and glucose metabolism in the patients with newly diagnosed type 2 diabetes (T2D). Methods: A total of 532 participants, including 387 patients with newly diagnosed T2D and 145 healthy controls, were recruited in the present study. PTH and metabolic parameters were measured in all participants. Results: The PTH levels were significantly lower in the newly diagnosed T2D patients compared with the control group (35.10 (25.90, 47.20) vs. 47.15 (35.83, 58.65) pg/ml, P < 0.001). The T2D patients with a higher glycated hemoglobin (HbA1c) tertile had lower PTH levels than the patients with a lower HbA1c tertile (32.90 (24.85, 41.40) vs. 37.50 (26.10, 54.55) pg/ml, P < 0.001). Spearman correlation analysis showed that PTH was positively correlated with the body mass index (BMI), fasting insulin (FINS), homeostasis model assessment of ß-cell function (HOMA-ß), and homeostasis model assessment of insulin resistance (HOMA-IR) and negatively correlated with HbA1c, blood calcium (Ca), blood phosphorus (P), and 25-hydroxyvitamin D3 (25-OH-D3). Multiple linear regression analysis demonstrated that PTH was significantly associated with HbA1c (ß = -1.475, P=0.003) and HOMA-ß (ß = 0.090, P=0.001) after adjusting for age, sex, BMI, season, 25-OH-D3, Ca, and P. Conclusion: PTH was negatively correlated with HbA1c in the newly diagnosed T2D patients. Our results suggested that the PTH level within the reference range is related to islet ß-cell function and hyperglycemia.

16.
Biomed Environ Sci ; 37(2): 228-232, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582987

RESUMO

As a reducing salt, sodium sulfite could deprive oxygen in solution, which could mimic hypoxic stress in Caenorhabditis elegans. In this study, the wild-type Escherichia coli strain MG1655 was used to examine the inhibition of sodium sulfite-induced hypoxia by observing the bacterial growth curves. We also analyzed the growth curves of mutant strains (for arcA/B, soxR/S, fnr, and oxyR) related to E. coli hypoxic pathways to reveal roles of the related genes during hypoxia. The ultrastructure of hypoxia-inhibited bacteria were also observed using transmission electron microscopy. Sodium sulfite could maintain hypoxic condition of bacterial culture for 8 h with concentrations over 40 mmol/L. Complete ultrastructure of the bacteria indicated sodium sulfite did inhibit bacterial growth and division. Among the hypoxia genes, fnr and arcB played key roles in sodium sulfite-induced hypoxia. This study showed that sodium sulfite could be used as a novel hypoxia revulsant for bacterial cultures.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Sulfitos , Humanos , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Hipóxia , Regulação Bacteriana da Expressão Gênica
17.
Nat Commun ; 15(1): 3172, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609373

RESUMO

Hydrotreating renewable oils over sulfided metal catalysts is commercially applied to produce green diesel, but it requires a continuous sulfur replenishment to maintain catalyst activity, which inevitably results in sulfur contamination and increases production costs. We report a robust P-doped NiAl-oxide catalyst with frustrated Lewis pairs (i.e., P atom bonded with the O atom acts as an electron donor, while the spatially separated Ni atom acts as an electron acceptor) that allows efficient green diesel production without sulfur replenishment. The catalyst runs more than 500 h at a weight hourly space velocity (WHSV) of 28.3 h-1 without deactivation (methyl laurate as a model compound), and is able to completely convert a real feedstock of soybean oil to diesel-range hydrocarbons with selectivity >90% during 500 h of operation. This work is expected to open up a new avenue for designing non-sulfur catalysts that can make the green diesel production greener.

18.
Life Sci ; 346: 122635, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615745

RESUMO

The signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, resides in the nucleus to regulate genes essential for vital cellular functions, including survival, proliferation, self-renewal, angiogenesis, and immune response. However, continuous STAT3 activation in tumor cells promotes their initiation, progression, and metastasis, rendering STAT3 pathway inhibitors a promising avenue for cancer therapy. Nonetheless, these inhibitors frequently encounter challenges such as cytotoxicity and suboptimal biocompatibility in clinical trials. A viable strategy to mitigate these issues involves delivering STAT3 inhibitors via drug delivery systems (DDSs). This review delineates the regulatory mechanisms of the STAT3 signaling pathway and its association with cancer. It offers a comprehensive overview of the current application of DDSs for anti-STAT3 inhibitors and investigates the role of DDSs in cancer treatment. The conclusion posits that DDSs for anti-STAT3 inhibitors exhibit enhanced efficacy and reduced adverse effects in tumor therapy compared to anti-STAT3 inhibitors alone. This paper aims to provide an outline of the ongoing research and future prospects of DDSs for STAT3 inhibitors. Additionally, it presents our insights on the merits and future outlook of DDSs in cancer treatment.

19.
Aging (Albany NY) ; 16(7): 5949-5966, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38526326

RESUMO

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with painful bladder. At present, the pathogenesis of IC/BPS is still unknown. Quercetin (QCT) is a kind of natural flavonoid with wide sources and multiple biological activities. The purpose of this study was to explore the effects of QCT on mRNA expression and related regulatory signal pathways in IC model rats. METHODS: LL-37 was used to induce the IC/BPS model rats. 20 mg/kg QCT was injected intraperitoneally into IC/BPS rats. ELISA, HE, Masson and TB staining were used to evaluate the level of inflammation and pathology. The concentration of QCT in rats was detected by HPLC. The mRNA sequencing was used to detect the differentially expressed (DE) mRNA in each group. The over-expression experiment of Lpl was carried out in IC/BPS model rats. RESULTS: QCT treatment significantly decreased the level of MPO, IL-1ß, IL-6 and TNF-α induced by LL-37 in rats, and alleviated bladder injury and mast cell degranulation. There were significant differences in mRNA sequencing data between groups, and the hub gene Lpl were screened by Cytohubba. The expression of Lpl was downregulated in IC/BPS rats. QCT intervention promoted Lpl expression. Overexpression of Lpl reduced the bladder injury induced by LL-37, increased GAG level and decreased the expression of MPO, IL-1ß, IL-6 and TNF-α. CONCLUSION: In this study, we provided the DE mRNA in IC/BPS rats treated with QCT, the signaling pathways for DE enrichment, screened out the hub genes, and revealed that Lpl overexpression alleviated IC/BPS model rats.


Assuntos
Biologia Computacional , Cistite Intersticial , Quercetina , RNA Mensageiro , Transdução de Sinais , Cistite Intersticial/tratamento farmacológico , Cistite Intersticial/genética , Cistite Intersticial/metabolismo , Animais , Quercetina/farmacologia , Ratos , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Feminino , Ratos Sprague-Dawley , Modelos Animais de Doenças
20.
Int J Biol Macromol ; 266(Pt 1): 131245, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38554922

RESUMO

Plant polysaccharides, distinguished by diverse glycosidic bonds and various cyclic sugar units, constitute a subclass of primary metabolites ubiquitously found in nature. Contrary to common understanding, plant polysaccharides typically form hydrocolloids upon dissolution in water, even though both excessively high and low temperatures impede this process. Bletilla striata polysaccharides (BSP), chosen for this kinetic study due to their regular repeating units, help elucidate the relationship between polysaccharide gelation and temperature. It is suggested that elevated temperatures enhance the mobility of BSP molecular chains, resulting in a notable acceleration of hydrogen bond breakage between BSP and water molecules and consequently, compromising the conformational stability of BSPs to some extent. This study unveils the unique relationship between polysaccharide dissolution processes and temperature from a kinetics perspective. Consequently, the conclusion provides a dynamical basis for comprehending the extraction and preparation of natural plant polysaccharide hydrocolloids, pharmaceuticals and related fields.

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