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1.
Adv Sci (Weinh) ; : e2403461, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992955

ABSTRACT

The precise mechanism underlying the therapeutic effects of dihydroartemisinin (DHA) in alleviating colitis remains incompletely understood. A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP)+/S100 calcium binding protein B (S100ß)+ enteric glial cells (EGCs) in inflamed colonic tissues and the disruption of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) observed in chronic colitis. DHA demonstrated efficacy in restoring the functionality of the dual gut barrier while concurrently attenuating intestinal inflammation. Mechanistically, DHA inhibited the transformation of GFAP+ EGCs into GFAP+/S100ß+ EGCs while promoting the differentiation of GFAP+/S100ß+ EGCs back into GFAP+ EGCs. Furthermore, DHA induced apoptosis in GFAP+/S100ß+ EGCs by inducing cell cycle arrest at the G0/G1 phase. The initial mechanism is further validated that DHA regulates EGC heterogeneity by improving dysbiosis in colitis. These findings underscore the multifaceted therapeutic potential of DHA in ameliorating colitis by improving dysbiosis, modulating EGC heterogeneity, and preserving gut barrier integrity, thus offering promising avenues for novel therapeutic strategies for inflammatory bowel diseases.

2.
Water Res ; 261: 122035, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38981352

ABSTRACT

Calcium-induced agglomeration of anaerobic granular sludge bed (AGSB) has become a critical factor in performance decline of calcified anaerobic reactors. However, the agglomeration process of AGSB and the underlying mechanisms remain unclear and elusive. This study delved into the evolution of calcified AGSB, and four typical states of normal AGSB (Nor-AGSB), calcified dispersed AGSB (Dis-AGSB), calcified dimeric AGSB (Dim-AGSB), and calcified polymeric AGSB (Pol-AGSB) were characterized. It was found that the minimum transport velocity of Dis-AGSB was 3.14-3.79 times higher than that of Nor-AGSB, and surpassed both the superficial velocity and the bubble-induced wake velocity. This led to the sedimentation of AGS at the bottom of reactor, resulting in stable contacts with each other. Solid fillers between AGS, namely cement, were observed within Dim-AGSB and Pol-AGSB, and could be classified as tightly- and loosely- bonded cement (T- and L-cement). Further analysis revealed that T-cement was rich in extracellular polymeric substances and intertwining pili/flagella, serving as the primary driving force for robust inter-AGS adhesion. While the L-cement was primarily in the form of calcite precipitation, and blocked the convective mass transfer pathways in Pol-AGSB, leading to the decreased convective mass transfer capacity. The critical distance between calcite and AGS was further revealed as 5.33 nm to form stable initial adhesion. Consequently, the agglomeration mechanism involving the evolution of AGSB was proposed as calcium-induced sedimentation, calcium-induced adhesion, and calcium-induced stasis in order. This study is expected to offer deep insight into the calcium-induced agglomeration especially from the overlooked perspective of AGSB, and provides feasible control strategies to manage the pressing calcification issues in engineering applications.

4.
Thromb Haemost ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009008

ABSTRACT

BACKGROUND: Disruptions in the pathways for activating and deactivating proteases in the bloodstream can lead to thrombosis and bleeding issues. Leucine aminopeptidases (LAPs), which are exopeptidases essential for regulating protein and peptide activities, are recognized as clinical biomarkers for liver diseases. However, the relationship between serum LAP activity and the risks of bleeding or thrombosis, as well as the identification of the specific tissues or organs that control LAP levels, is not well understood. METHODS: We performed a retrospective study to evaluate serum LAP activities in 149,360 patients with 47 different diseases and 9,449 healthy individuals. The analysis was conducted using SPSS V2.6, RStudio V.1.3.1073, and libraries in Python 3.8. RESULTS: Our research revealed that 21 of the 47 diseases studied showed increased median serum LAP activities, while 26 diseases were associated with significantly lower activities, especially those related to thrombosis. Furthermore, most diseases were found to have an increased risk of bleeding and thrombosis, indicated by higher Q25 and lower Q75 LAP activities compared to the control group. ROC analysis confirmed the effectiveness of LAP activities as biomarkers for specific conditions like hepatic encephalopathy, liver cancer, pancreatitis, and pancreatic cancer. Diseases were categorized into clusters with similar bleeding or thrombotic tendencies through principal component analysis. CONCLUSION: This study highlighted regulatory influence of the liver and pancreas on LAP levels. The established link between serum LAP concentrations and the risk of bleeding or thrombosis paved the way for the development of diagnostic and preventative approaches for various medical conditions.

5.
Stroke ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946544

ABSTRACT

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

6.
Cancer Innov ; 3(3): e118, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38947755

ABSTRACT

Background: Cancer-targeted T-cell receptor T (TCR-T) cells hold promise in treating cancers such as hematological malignancies and breast cancers. However, approaches to obtain cancer-reactive TCR-T cells have been unsuccessful. Methods: Here, we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune fingerprints. Rare steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells, and then the expanded cells were applied to establish humanized mice. The human immune system was evaluated according to the kinetics of dendritic cells, monocytes, T-cell subsets, and cytokines. To fully stimulate the immune response and to obtain B-cell precursor NAML-6- and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells, we used the inactivated cells above to treat humanized mice twice a day every 7 days. Then, human T cells were processed for TCR ß-chain (TRB) sequencing analysis. After the repertoires had been constructed, features such as the fraction, diversity, and immune signature were investigated. Results: The results demonstrated an increase in diversity and clonality of T cells after treatment. The preferential usage and features of TRBV, TRBJ, and the V-J combination were also changed. The stress also induced highly clonal expansion. Tumor burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized mice. Conclusions: We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T pools. Our platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells. It therefore has the potential to greatly benefit cancer treatment.

7.
Bioresour Technol ; : 131090, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986880

ABSTRACT

To reveal the key enzymes in the nitrogen removal pathway and to further elucidate the mechanism of the catalytic reaction, this study utilized metaproteomics combined with molecular dynamics and density functional theory calculation. K. stuttgartiensis provided the proteins up to 88.37 % in the anammox-based system. Hydrazine synthase (HZS) and hydrazine dehydrogenase (HDH) accounted for 15.94 % and 3.45 % of the total proteins expressed by K. stuttgartiensis, thus were considered as critical enzymes in the nitrogen removal pathway. The process of HZSγ binding to NO with lowest binding free energy of -4.91 ±â€¯1.33 kJ/mol. The reaction catalyzed by HZSα was calculated to be the rate-limiting catalyzing step, because it transferred the proton from NH3 to ·OH by crossing an energy barrier of up to 190.29 kJ/mol. This study provided molecular level insights to enhance the performance of nitrogen removal in anammox-based system.

8.
Cell Death Differ ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987382

ABSTRACT

Cuproptosis is characterized by the aggregation of lipoylated enzymes of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. As dysregulation of copper homeostasis can induce cuproptosis, there is emerging interest in exploiting cuproptosis for cancer therapy. However, the molecular drivers of cancer cell evasion of cuproptosis were previously undefined. Here, we found that cuproptosis activates the Wnt/ß-catenin pathway. Mechanistically, copper binds PDK1 and promotes its interaction with AKT, resulting in activation of the Wnt/ß-catenin pathway and cancer stem cell (CSC) properties. Notably, aberrant activation of Wnt/ß-catenin signaling conferred resistance of CSCs to cuproptosis. Further studies showed the ß-catenin/TCF4 transcriptional complex directly binds the ATP7B promoter, inducing its expression. ATP7B effluxes copper ions, reducing intracellular copper and inhibiting cuproptosis. Knockdown of TCF4 or pharmacological Wnt/ß-catenin blockade increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. These findings reveal a link between copper homeostasis regulated by the Wnt/ß-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction.

9.
Biomed Environ Sci ; 37(6): 607-616, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38988111

ABSTRACT

Objective: Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on asthma, which is often comorbid with type 2 diabetes mellitus (T2DM) and obesity. Therefore, we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1 (GLP-1) receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity. Methods: PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov were systematically searched from inception to July 2023. Randomized controlled trials (RCTs) of GLP-1 receptor-based agonists (GLP-1RA, GLP-1 based dual and triple receptor agonist) with reports of asthma events were included. Outcomes were computed as risk ratios ( RR) using a fixed-effects model. Results: Overall, 39 RCTs with a total of 85,755 participants were included. Compared to non-GLP-1 receptor-based agonist users, a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments, although the difference was not statistically significant [ RR = 0.91, 95% confidence interval ( CI): 0.68 to 1.24]. Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users ( RR = 0.65, 95% CI: 0.43 to 0.99, P = 0.043). We also performed sensitivity analyses for participant characteristics, study design, drug structure, duration of action, and drug subtypes. However, no significant associations were observed. Conclusion: Compared with non-users, a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments. Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.


Subject(s)
Asthma , Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Obesity , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Asthma/drug therapy , Asthma/epidemiology , Humans , Glucagon-Like Peptide-1 Receptor/agonists , Obesity/complications , Incidence , Hypoglycemic Agents/therapeutic use
10.
MycoKeys ; 106: 303-325, 2024.
Article in English | MEDLINE | ID: mdl-38993357

ABSTRACT

Species of the family Microdochiaceae (Xylariales, Sordariomycetes) have been reported from worldwide, and collected from different plant hosts. The proposed new genus and two new species, viz., Macroidriella gen. nov., M.bambusae sp. nov. and Microdochiumaustrale sp. nov., are based on multi-locus phylogenies from a combined dataset of ITS rDNA, LSU, RPB2 and TUB2 with morphological characteristics. Microdochiumsinense has been collected from diseased leaves of Phragmitesaustralis and this is the first report of the fungus on this host plant. Simultaneously, we annotated 10,372 to 11,863 genes, identified 4,909 single-copy orthologous genes, and conducted phylogenomic analysis based on genomic data. A gene family analysis was performed and it will expand the understanding of the evolutionary history and biodiversity of the Microdochiaceae. The detailed descriptions and illustrations of species are provided.

11.
Theranostics ; 14(10): 3810-3826, 2024.
Article in English | MEDLINE | ID: mdl-38994034

ABSTRACT

Rationale: Surgical resection is a primary treatment for solid tumors, but high rates of tumor recurrence and metastasis post-surgery present significant challenges. Manganese (Mn2+), known to enhance dendritic cell-mediated cancer immunotherapy by activating the cGAS-STING pathway, has potential in post-operative cancer management. However, achieving prolonged and localized delivery of Mn2+ to stimulate immune responses without systemic toxicity remains a challenge. Methods: We developed a post-operative microenvironment-responsive dendrobium polysaccharide hydrogel embedded with Mn2+-pectin microspheres (MnP@DOP-Gel). This hydrogel system releases Mn2+-pectin microspheres (MnP) in response to ROS, and MnP shows a dual effect in vitro: promoting immunogenic cell death and activating immune cells (dendritic cells and macrophages). The efficacy of MnP@DOP-Gel as a post-surgical treatment and its potential for immune activation were assessed in both subcutaneous and metastatic melanoma models in mice, exploring its synergistic effect with anti-PD1 antibody. Result: MnP@DOP-Gel exhibited ROS-responsive release of MnP, which could exert dual effects by inducing immunogenic cell death of tumor cells and activating dendritic cells and macrophages to initiate a cascade of anti-tumor immune responses. In vivo experiments showed that the implanted MnP@DOP-Gel significantly inhibited residual tumor growth and metastasis. Moreover, the combination of MnP@DOP-Gel and anti-PD1 antibody displayed superior therapeutic potency in preventing either metastasis or abscopal brain tumor growth. Conclusions: MnP@DOP-Gel represents a promising drug-free strategy for cancer post-operative management. Utilizing this Mn2+-embedding and ROS-responsive delivery system, it regulates surgery-induced immune responses and promotes sustained anti-tumor responses, potentially increasing the effectiveness of surgical cancer treatments.


Subject(s)
Dendrobium , Hydrogels , Manganese , Mice, Inbred C57BL , Microspheres , Polysaccharides , Animals , Mice , Hydrogels/chemistry , Manganese/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Dendrobium/chemistry , Macrophages/immunology , Macrophages/drug effects , Melanoma/immunology , Melanoma/drug therapy , Melanoma/therapy , Immunotherapy/methods , Dendritic Cells/immunology , Dendritic Cells/drug effects , Cell Line, Tumor , Female , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Reactive Oxygen Species/metabolism , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/pharmacology , Melanoma, Experimental/immunology , Melanoma, Experimental/therapy , Melanoma, Experimental/drug therapy
12.
World J Gastrointest Oncol ; 16(6): 2610-2630, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994168

ABSTRACT

BACKGROUND: Gastric signet ring cell carcinoma (GSRC) represents a specific subtype of gastric cancer renowned for its contentious epidemiological features, treatment principles, and prognostic factors. AIM: To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC (LAGSRC) after surgery. METHODS: The annual rates of GSRC incidence and mortality, covering the years 1975 to 2019, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software. The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates. The Cox regression model was used to explore the independent prognostic factors for overall survival (OS). The risk factors extracted were used to establish a prognostic nomogram. RESULTS: The overall incidence of GSRC increased dramatically between 1975 and 1998, followed by a significant downward trend in incidence after 1998. In recent years, there has been a similarly optimistic trend in GSRC mortality rates. The trend in GSRC showed discrepancies based on age and sex. Receiver operating characteristic curves, calibration curves, and decision curve analysis for 1-year, 3-year, and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram. The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system. CONCLUSION: The model we established can aid clinicians in the early prognostication of LAGSRC patients, resulting in improved clinical outcomes by modifying management strategies and patient health care.

14.
Exp Ther Med ; 28(3): 347, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39006451

ABSTRACT

The aim of the present study was to compare flexible ureteroscopy and laparoscopy in the treatment of peripelvic renal cysts, so as to determine the best treatment method for patients with peripelvic renal cysts. A systematic search of the PubMed, EMBASE, Cochrane Library, CONAHL, Clinicaltrials.gov, Google Scholar, CNKI and WanFang DATA databases was conducted for articles published over 22 years (December 1980-December 2022) using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. By searching the database, a total of 594 studies were found, of which eight were analyzed as evidence. A total of 394 patients were included in the present study. Of these, 193 were treated laparoscopically and 201 were treated by flexible ureteroscopy. In terms of analysis results, radiation reexamination after laparoscopic therapy had a higher success rate. Ureteroscopy has advantages in the time spent in the operation, the amount of blood lost during the operation, the time to recover the anal exhaust after the operation and the length of postoperative hospital stay. There were no significant difference in postoperative recurrence or complications between the two surgical methods. After comprehensive analysis, it was considered that flexible ureteroscopy has more advantages in the treatment of peripelvic renal cyst, which is mainly manifested in the duration of operation, the total amount of blood loss during operation, the interval of recovery of anal exhaust after operation and the total length of postoperative hospital stay. It is worth further exploration and promotion.

15.
Int J Biol Macromol ; 276(Pt 1): 133769, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992533

ABSTRACT

This work aimed to develop and characterize a novel bi-layer film (BIF) for monitoring the freshness of salmon. The indicator layer consists of carrageenan (Car), pectin (PEC) and purple sweet potato anthocyanin (PSPA), and the antibacterial layer consists of Car and magnolol (Mag). The results showed that the Car/Mag2 had the optimal water resistance: the static water contact angle of 80.36 ± 0.92 °, moisture content of 31.38 ± 0.86 %, swelling degree of 92.96 ± 0.46 %, and water solubility of 40.08 ± 1.17 %, and showed excellent antibacterial properties against E. coli and S. aureus with antibacterial rate of 86.13 % ± 0.10 % and 97.53 % ± 0.02 %, respectively. Then BIFs with different PSPA concentration were tested. The morphology, mechanical and water vapor properties (WVP) of the BIFs were studied, and its application in salmon preservation was evaluated. The mechanical properties and WVP test results showed that the BIF0.2 had the optimal Tensile strength (TS) and WVP values. The BIFs showed distinguishable color changes between the pH ranges of 3-10. The shelf life of salmon packaged by BIF0.2 was prolonged by 2 days. Moreover, the BIF0.2 was able to effectively monitor salmon freshness. In conclusion, the BIF has great potential for monitoring salmon meat freshness.

16.
Psych J ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38965885

ABSTRACT

Reward processing dysfunction and inhibition control deficiency have been observed in Internet gaming disorder (IGD). However, it is still unclear whether the previous reinforcement learning depends on reward/punishment feedback influences on the cognitive inhibitory control of IGD. This study compared the differences between an IGD group and healthy people without game experiences in the probability selection task and the subsequent stop signal task by the method of behavioral experiments, in order to explore whether the reward learning ability is impaired in the IGD group. We also discuss the influence of previous reward learning on subsequent inhibition control. The results showed that (1) during the reward learning phase, the IGD group's accuracy was significantly lower than that of the control group; (2) compared with the control group, the IGD group's reaction times were longer in the transfer phase; (3) for no-go trials of the inhibitory control phase after reward learning, the accuracy of the reward-related stimulation in the IGD group was lower than that of punishment-related or neutral stimulation, but there was no significant difference among the three conditions in the control group. These findings indicated that the reinforcement learning ability of the IGD group was impaired, which further caused the abnormal response to reinforcement stimuli.

17.
Adv Exp Med Biol ; 1445: 119-128, 2024.
Article in English | MEDLINE | ID: mdl-38967754

ABSTRACT

Immunoglobulins (Igs) have been widely accepted to be exclusively expressed by B cells. Nonetheless, this theory is challenged by mounting evidence which suggests that Igs can also be generated by non B cells (non B-Ig), including cardiomyocytes (CM). Non B-Ig exhibits unique physical and chemical characteristics, unique variable region sequences and functions, which diverge from those of B-Ig. For instance, non B-Ig demonstrates hydrophobicity, limited diversity in the variable region, and extracellular matrix protein activity. Likewise, cardiomyocytes can express different classes of Igs, including IgM, IgG, and free Igκ light chains (cardiomyocyte derived-Igs, CM-Igs). In particular, CM-Igs can be secreted into the extracellular space in various cardiovascular diseases, such as myocardial ischaemia and myocardial fibrosis where they might be involved in complement activation and direct damage to cardiomyocytes. Nevertheless, the precise pathological activity of CM-Igs remains unclear. Recently, Zhu et al. focused on studying the sequence characteristics and functions of CM-Igκ; they discovered that the CM-Igκ exhibits a unique VJ recombination pattern, high hydrophobicity, and is principally located on the intercalated discs and cross striations of the cardiomyocytes. Interestingly, loss of Igκ in cardiomyocytes results in structural disorders in intercalated discs and dysfunction in myocardial contraction and conduction. Mechanically, Igκ promotes the stabilisation of plectin, a cytoskeleton cross-linker protein that connects desmin to desomsome, to maintain the normal structure of the intercalated disc. This finding indicates that CM-Igκ plays an integral role in maintaining cytoskeleton structure. Consequently, it is imperative to reveal the physiological functions and mechanisms of pathological injury associated with CM-Igs.


Subject(s)
Immunoglobulins , Myocytes, Cardiac , Humans , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Animals , Immunoglobulins/metabolism , Immunoglobulins/genetics , Clinical Relevance
18.
Braz J Med Biol Res ; 57: e13357, 2024.
Article in English | MEDLINE | ID: mdl-38958364

ABSTRACT

The overexpression of P-glycoprotein (P-gp/ABCB1) is a leading cause of multidrug resistance (MDR). Hence, it is crucial to discover effective pharmaceuticals that counteract ABCB1-mediated multidrug resistance. FRAX486 is a p21-activated kinase (PAK) inhibitor. The objective of this study was to investigate whether FRAX486 can reverse ABCB1-mediated multidrug resistance, while also exploring its mechanism of action. The CCK8 assay demonstrated that FRAX486 significantly reversed ABCB1-mediated multidrug resistance. Furthermore, western blotting and immunofluorescence experiments revealed that FRAX486 had no impact on expression level and intracellular localization of ABCB1. Notably, FRAX486 was found to enhance intracellular drug accumulation and reduce efflux, resulting in the reversal of multidrug resistance. Docking analysis also indicated a strong affinity between FRAX486 and ABCB1. This study highlights the ability of FRAX486 to reverse ABCB1-mediated multidrug resistance and provides valuable insights for its clinical application.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B , Breast Neoplasms , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Humans , Drug Resistance, Neoplasm/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , ATP Binding Cassette Transporter, Subfamily B/metabolism , ATP Binding Cassette Transporter, Subfamily B/antagonists & inhibitors , Drug Resistance, Multiple/drug effects , Female , p21-Activated Kinases/antagonists & inhibitors , p21-Activated Kinases/metabolism , Cell Line, Tumor , Blotting, Western
19.
Chem Asian J ; : e202400554, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956446

ABSTRACT

A six-cyclic crown ether-type pillar[5]arene was synthesized, and the five ethylene oxide loops were located outside the cavity and not affected by temperature changes which was confirmed by variable-temperature NMR experiment in DMSO-d6 and CDCl3 and 2D 1H-1H NOESY experiment in CDCl3. The six-cyclic pillar[5]-crown also showed greater binding ability of host-guest with bis(pyridinium) derivatives than conventional alkoxy pillar[5]arenes that illustrated through 1H NMR titration spectroscopic experiment in acetone-d6/CDCl3 (1:1) and UV-vis titration experiments in CHCl3 at room temperature. The five benzocrown ethers at the periphery were able to bind metal cations by 1H NMR titration spectroscopic experiment in CD2Cl2/methanol-d4(9:1).

20.
Food Chem ; 458: 140329, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38991239

ABSTRACT

Recently, fiber-based and functional paper food packaging has garnered significant attention for its versatility, excellent performance, and potential to provide sustainable solutions to the food packaging industry. Fiber-based food packaging is characterized by its large surface area, adjustable porosity and customizability, while functional paper-based food packaging typically exhibits good mechanical strength and barrier properties. This review summarizes the latest research progress on food packaging based on fibers and functional paper. Firstly, the raw materials used for preparing fiber and functional paper, along with their physical and chemical properties and roles in food packaging, were discussed. Subsequently, the latest advancements in the application of fiber and paper materials in food packaging were introduced. This paper also discusses future research directions and potential areas for improvement in fiber and functional paper food packaging to further enhance their effectiveness in ensuring food safety, quality, and sustainability.

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