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1.
J Zhejiang Univ Sci B ; 25(9): 789-795, 2024 Aug 19.
Article in English, Chinese | MEDLINE | ID: mdl-39308068

ABSTRACT

Selenium nanoparticles (SeNPs) have garnered extensive research interest and shown promising applications across diverse fields owing to their distinctive properties, including antioxidant, anticancer, and antibacterial activity (Ojeda et al., 2020; Qu et al., 2023; Zambonino et al., 2021, 2023). Among the various approaches employed for SeNP synthesis, green synthesis has emerged as a noteworthy and eco-friendly methodology. Keshtmand et al. (2023) underscored the significance of green-synthesized SeNPs, presenting a compelling avenue in this domain. This innovative strategy harnesses the potential of natural resources, such as plant extracts or microorganisms, to facilitate the production of SeNPs.


Subject(s)
Bacillus , Green Chemistry Technology , Selenium , Selenium/chemistry , Bacillus/metabolism , Metal Nanoparticles/chemistry , Nanoparticles/chemistry , Antioxidants/chemistry
2.
J Zhejiang Univ Sci B ; : 1-7, 2024 Aug 13.
Article in English, Chinese | MEDLINE | ID: mdl-39155546

ABSTRACT

Selenium nanoparticles (SeNPs) have garnered extensive research interest and shown promising applications across diverse fields owing to their distinctive properties, including antioxidant, anticancer, and antibacterial activity (Ojeda et al., 2020; Qu et al., 2023; Zambonino et al., 2021, 2023). Among the various approaches employed for SeNP synthesis, green synthesis has emerged as a noteworthy and eco-friendly methodology. Keshtmand et al. (2023) underscored the significance of green-synthesized SeNPs, presenting a compelling avenue in this domain. This innovative strategy harnesses the potential of natural resources, such as plant extracts or microorganisms, to facilitate the production of SeNPs.

3.
Ultrason Sonochem ; 110: 107047, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39208591

ABSTRACT

Air-dried beef, a traditional dry fermented meat product in China, whose quality is largely influenced by processing conditions. In this study, contact ultrasound (CU) and infrared radiation (IR) were employed to enhance hot air drying (HAD), with an investigation into the mechanisms underlying improvements in quality and flavor. Samples subjected to CU and IR treatments during HAD (CU-IRD) demonstrated superior color (L* = 42.68, a* = 5.05, b* = -3.86) and tenderness (140.59 N) than HAD group, primarily attributed to reduced drying times and alterations in ultrastructure. Analyses utilizing SDS-PAGE and total volatile basic nitrogen (TVB-N) revealed that HAD and CU-HAD resulted in significant protein oxidation (197.85 mg TVB-N/kg and 202.23 mg TVB-N/kg, respectively), while IR treatments were associated with increased thermal degradation of proteins, producing lower molecular weight peptides. Compared with HAD group, the activities of certain lipases and proteases were enhanced by ultrasound and infrared treatments, leading to the release of greater amounts of free fatty acids and flavor amino acids. Furthermore, the thermal effects of infrared and the cavitation effects of ultrasound contributed to increased fat oxidation, amino acid Strecker degradation, and esterification reactions, thereby augmenting the diversity and concentration of volatile flavor compounds, including alkanes, ketones, aldehydes, and esters. These findings indicate that the synergistic application of CU and IR represents a promising strategy for enhancing the quality of air-dried beef.


Subject(s)
Desiccation , Hot Temperature , Infrared Rays , Cattle , Animals , Desiccation/methods , Ultrasonic Waves , Air , Food Quality , Taste , Red Meat/analysis , Food Handling/methods
4.
Ultrason Sonochem ; 108: 106978, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38971086

ABSTRACT

Drying, as a critical step in the production of air-dried beef, has a direct impact on the quality of the final product. Innovatively, a composite system incorporating contact ultrasound (CU) and infrared radiation (IR) as auxiliary measures within a hot air drying (HAD) framework was built in this research, and the effects of these techniques on the drying kinetics, protein denaturation, and moisture transformation of air-dried beef were investigated. In comparison to HAD treatment, the integrated CU and IR (CU-IRD) system displayed marked enhancements in heat and moisture transport efficiency, thereby saving 36.84% of time expenditure and contributing favorably to the improved moisture distribution of the end-product. This was mainly ascribed to the denaturation of myosin induced by IR thermal effect and the micro-channel produced by CU sponge effect, thus increasing T2 relaxation time and the proportion of free water. In conclusion, the composite system solved the problem of surface hardening and reduces hardness and chewiness of air-dried beef by 40.42% and 45.25% respectively, but inevitably increased the energy burden by 41.60%.


Subject(s)
Air , Desiccation , Infrared Rays , Water , Water/chemistry , Kinetics , Desiccation/methods , Cattle , Animals , Ultrasonic Waves , Hot Temperature , Red Meat , Physical Phenomena
5.
Int J Biol Macromol ; 275(Pt 1): 133232, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38960234

ABSTRACT

Spindle migration and assembly regulates asymmetric oocyte division, which is essential for fertility. Fbxo28, as a member of SCF (Skp1-Cul1-F-box) ubiquitin E3 ligases complex, is specifically expressed in oocytes. However, little is known about the functions of Fbxo28 in spindle assembly and migration during oocyte meiosis I. In present study, microinjection with morpholino oligonucleotides and exogenous mRNA for knockdown and rescue experiments, and immunofluorescence staining, western blot, timelapse confocal microscopy and chromosome spreading were utilized to explore the roles of Fbxo28 in asymmetric division during meiotic maturation. Our data suggested that Fbxo28 mainly localized at chromosomes and acentriolar microtubule-organizing centers (aMTOCs). Depletion of Fbxo28 did not affect polar body extrusion but caused defects in spindle morphology and migration, indicative of the failure of asymmetric division. Moreover, absence of Fbxo28 disrupted both cortical and cytoplasmic actin assembly and decreased the expression of ARPC2 and ARP3. These defects could be rescued by exogenous Fbxo28-myc mRNA supplement. Collectively, this study demonstrated that Fbxo28 affects spindle morphology and actin-based spindle migration during mouse oocyte meiotic maturation.


Subject(s)
F-Box Proteins , Meiosis , Oocytes , Spindle Apparatus , Animals , Oocytes/metabolism , Oocytes/cytology , Mice , Spindle Apparatus/metabolism , F-Box Proteins/metabolism , F-Box Proteins/genetics , Female , Actins/metabolism , Microtubule-Organizing Center/metabolism
6.
Reprod Toxicol ; 128: 108634, 2024 09.
Article in English | MEDLINE | ID: mdl-38851359

ABSTRACT

Vinorelbine is a commonly used drug to treat various malignancies, such as breast cancer, non-small cell lung cancer, and metastatic pleural mesothelioma. Its side effects include severe neutropenia, local phlebitis, gastrointestinal reactions, and neurotoxicity. In view of the scarcity of research on vinorelbine's reproductive toxicity, this study evaluated the impact of vinorelbine ditartrate, a commonly used form of vinorelbine, on oocyte maturation in vitro. Our investigation revealed that vinorelbine ditartrate had no effect on oocyte meiotic resumption. However, it did reduce the rate of first polar body extrusion, suggesting that it could significantly impede the meiotic maturation of oocytes. Vinorelbine ditartrate exposure was found to disturb the regular spindle assembly and chromosome alignment, leading to the continuous activation of the spindle assembly checkpoint (SAC) and a delayed activation of the anaphase-promoting complex/cyclosome (APC/C), ultimately causing aneuploidy in oocytes. Consequently, the administration of vinorelbine is likely to result in oocyte aneuploidy, which can be helpful in providing a drug reference and fertility guidance in a clinical context.


Subject(s)
Aneuploidy , Antineoplastic Agents, Phytogenic , Meiosis , Oocytes , Vinorelbine , Vinorelbine/toxicity , Oocytes/drug effects , Animals , Female , Meiosis/drug effects , Antineoplastic Agents, Phytogenic/toxicity , Mice , Anaphase-Promoting Complex-Cyclosome , Spindle Apparatus/drug effects
7.
Aerosp Med Hum Perform ; 95(7): 381-389, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38915172

ABSTRACT

INTRODUCTION: Most airline pilots reported having suffered from sleep disorders and fatigue due to circadian disruption, a potential risk to flight safety. This study attempted to uncover the actual scenario of circadian disruption and working load status among airline pilots.METHODS: In study 1, 21 pilots were invited to participate in a 14-d sleep monitoring and a dual 2-back test to monitor their sleep patterns and cognitive function level. To provide an in-depth view, data from scheduled flights, including 567 airline pilots, was analyzed in Study 2. The present study used cluster analysis to reflect the distribution of the flight scheduling characteristics, including working time and actual working hours. A simulation model was then developed to predict the pilots' 1-mo sleep-wake pattern.RESULTS: The results indicated that sleep problems were prevalent in this population, especially the night before an earlier morning shift. Regarding the cognitive test, they scored the lowest on earlier morning shifts compared with daytime and evening shifts. It was found that over 70% of the flight schedules can lead to circadian disruption, and 47.44% of the pilots worked under high-load status.DISCUSSION: Airline pilots inevitably work irregular hours and the current policies for coping with circadian disruption seem inefficient. This study thus calls for urgency in improving scheduling and fatigue management systems from the circadian rhythm perspective.Yang SX, Cheng S, Sun Y, Tang X, Huang Z. Circadian disruption in civilian airline pilots. Aerosp Med Hum Perform. 2024; 95(7):381-389.


Subject(s)
Aerospace Medicine , Circadian Rhythm , Pilots , Work Schedule Tolerance , Humans , Male , Adult , Pilots/statistics & numerical data , Work Schedule Tolerance/physiology , Circadian Rhythm/physiology , Fatigue/physiopathology , Fatigue/etiology , Sleep Disorders, Circadian Rhythm/epidemiology , Sleep Disorders, Circadian Rhythm/physiopathology , Middle Aged , Sleep/physiology , Cognition/physiology , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/physiopathology
8.
J Phys Chem Lett ; 15(26): 6743-6749, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38912658

ABSTRACT

Layered sodium transition-metal oxides generally encounter severe capacity decay and inferior rate performance during cycling, especially at a high state of charge. Herein, defect concentration is rationally modulated to explore the impact on electrochemical behavior in NaNi1/3Fe1/3Mn1/3O2 layered oxides. Bulk vacancies are increased through annealing in an oxygen-rich atmosphere, demonstrated by electron paramagnetic resonance measurement. It is found that the cathode with enriched oxygen vacancies exhibits significantly enhanced reversibility of redox reactions with a higher initial Coulombic efficiency of 90.0%. Furthermore, the reduced volume variations during the initial charge/discharge process are also confirmed by in situ X-ray diffraction. As a result, the oxygen-vacancy-rich cathode shows great cycling stability and superior rate performances. Also, full cells deliver a specific capacity of approximately 145.2 mAh g-1 at 0.5 C, with a high capacity retention of 78.3% after 100 cycles. This work presents a viable strategy for designing Na+ intercalated cathodes with a high-energy density.

9.
J Ginseng Res ; 48(3): 298-309, 2024 May.
Article in English | MEDLINE | ID: mdl-38707638

ABSTRACT

Background: 20(S)-ginsenoside Rh2(GRh2), an effective natural histone deacetylase inhibitor, can inhibit acute myeloid leukemia (AML) cell proliferation. Lactate regulated histone lactylation, which has different temporal dynamics from acetylation. However, whether the high level of lactylation modification that we first detected in acute promyelocytic leukemia (APL) is associated with all-trans retinoic acid (ATRA) resistance has not been reported. Furthermore, Whether GRh2 can regulate lactylation modification in ATRA-resistant APL remains unknown. Methods: Lactylation and METTL3 expression levels in ATRA-sensitive and ATRA-resistant APL cells were detected by Western blot analysis, qRT-PCR and CO-IP. Flow cytometry (FCM) and APL xenograft mouse models were used to determine the effect of METTL3 and GRh2 on ATRA-resistance. Results: Histone lactylation and METTL3 expression levels were considerably upregulated in ATRA-resistant APL cells. METTL3 was regulated by histone lactylation and direct lactylation modification. Overexpression of METTL3 promoted ATRA-resistance. GRh2 ameliorated ATRA-resistance by downregulated lactylation level and directly inhibiting METTL3. Conclusions: This study suggests that lactylation-modified METTL3 could provide a promising strategy for ameliorating ATRA-resistance in APL, and GRh2 could act as a potential lactylation-modified METTL3 inhibitor to ameliorate ATRA-resistance in APL.

10.
Nat Commun ; 15(1): 4456, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796494

ABSTRACT

Charge, spin and Cooper-pair density waves have now been widely detected in exotic superconductors. Understanding how these density waves emerge - and become suppressed by external parameters - is a key research direction in condensed matter physics. Here we study the temperature and magnetic-field evolution of charge density waves in the rare spin-triplet superconductor candidate UTe2 using scanning tunneling microscopy/spectroscopy. We reveal that charge modulations composed of three different wave vectors gradually weaken in a spatially inhomogeneous manner, while persisting to surprisingly high temperatures of 10-12 K. We also reveal an unexpected decoupling of the three-component charge density wave state. Our observations match closely to the temperature scale potentially related to short-range magnetic correlations, providing a possible connection between density waves observed by surface probes and intrinsic bulk features. Importantly, charge density wave modulations become suppressed with magnetic field both below and above superconducting Tc in a comparable manner. Our work points towards an intimate connection between hidden magnetic correlations and the origin of the unusual charge density waves in UTe2.

11.
IEEE Trans Cybern ; PP2024 May 31.
Article in English | MEDLINE | ID: mdl-38819970

ABSTRACT

In this article, the method of dynamic performance monitoring and adaptive self-tuning of parameters for actual PID control systems of industrial processes in virtual reality scenes is proposed. This method combines the digital twin model of the PID control process based on system identification and adaptive deep learning and the PID tuning intelligent algorithm based on reinforcement learning with virtual reality and immersive interaction of industrial metaverse. An industrial metaverse-based intelligent PID tuning system is proposed by combining the above method with the end-edge-cloud collaboration technology of Industrial Internet. The challenging problem that the actual operating PID control system in complex industrial processes cannot be optimized online is solved. Using the energy-intensive equipment, the fused magnesium furnace, as an industrial object, we conducted comparative simulation experiments between the proposed control method and several advanced control methods, as well as industrial experiments for the proposed intelligent system. Simulation experiments demonstrate the effectiveness of the proposed control method. The industrial experimental results indicate that the performance monitoring and adaptive self-tuning of parameters for actual PID control systems of industrial processes in virtual reality scenes can be realized, which achieves excellent control effects.

12.
BMC Geriatr ; 24(1): 343, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622550

ABSTRACT

BACKGROUND: The first six months of therapy represents a high-risk period for peritoneal dialysis (PD) failure. The risk of death in the first six months is higher for older patients treated with urgent-start PD (USPD). However, there are still gaps in research on mortality and risk factors for death in this particular group of patients. We aimed to investigate mortality rates and risk factors for death in older patients with end-stage renal disease (ESRD) receiving USPD within and after six months of therapy. METHODS: We retrospectively studied the clinical information of older adults aged ≥ 65 years with ESRD who received USPD between 2013 and 2019 in five Chinese hospitals. Patients were followed up to June 30, 2020. The mortality and risk factors for death in the first six months of USPD treatment and beyond were analyzed. RESULTS: Of the 379 elderly patients in the study, 130 died over the study period. During the follow-up period, the highest number (45, 34.6%) of deaths occurred within the first six months. Cardiovascular disease was the most common cause of death. The baseline New York Heart Association (NYHA) class III-IV cardiac function [hazard ratio (HR) = 2.457, 95% confidence interval (CI): 1.200-5.030, p = 0.014] and higher white blood cell (WBC) count (HR = 1.082, 95% CI: 1.021-1.147, p = 0.008) increased the mortality risk within six months of USPD. The baseline NYHA class III-IV cardiac function (HR = 1.945, 95% CI: 1.149-3.294, p = 0.013), lower WBC count (HR = 0.917, 95% CI: 0.845-0.996, p = 0.040), lower potassium levels (HR = 0.584, 95% CI: 0.429-0.796, p = 0.001), and higher calcium levels (HR = 2.160, 95% CI: 1.025-4.554, p = 0.043) increased the mortality risk after six months of USPD. CONCLUSION: Different risk factors correlated with mortality in older adults with ESRD within and after six months of undergoing USPD, including baseline NYHA class III-IV cardiac function, WBC count, potassium, and calcium levels.


Subject(s)
Kidney Failure, Chronic , Peritoneal Dialysis , Aged , Humans , Retrospective Studies , Calcium , Peritoneal Dialysis/adverse effects , Renal Dialysis , Potassium , Risk Factors
13.
Toxicol Mech Methods ; 34(1): 20-31, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37621060

ABSTRACT

Nephrotoxicity induced by aristolochic acid I (AAI) is related to redox stress and apoptosis. Apurinic/apyrimidine endonuclease 1 (APE1) has antioxidant and anti-apoptotic effects. This study investigated the potential role of APE1 in AAI-induced nephrotoxicity. Renal injury was successfully induced in C57BL/6J mice by intraperitoneal injection of AAI every other day for 28 days. Expressions of APE1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) in renal tissues of the model mice was inhibited, accompanied by oxidative damage and apoptosis. Similar results were obtained in vitro in human proximal tubular (HK-2) cells damaged by AAI. In the presence of a low concentration of the APE1 inhibitor E3330, expression of Nrf2 and HO-1 proteins in HK-2 cells was decreased and AAI-induced apoptosis was aggravated. Overexpression of APE1 in HK-2 cells promoted the expression of Nrf2 and HO-1, and alleviated apoptosis and renal injury induced by AAI. The collective findings demonstrate that AAI can inhibit the induction of oxidative stress and apoptosis by the APE1/Nrf2/HO-1 axis, leading to AAI renal injury. Targeting APE1 may be an effective therapeutic strategy to treat AA nephrotoxicity.


Subject(s)
Aristolochic Acids , NF-E2-Related Factor 2 , Mice , Humans , Animals , NF-E2-Related Factor 2/metabolism , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Mice, Inbred C57BL , Oxidative Stress , Apoptosis , Aristolochic Acids/toxicity
14.
Heliyon ; 9(12): e22530, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38076176

ABSTRACT

High-entropy alloys (HEAs) have gained significant attentions in recent years, due to their unique properties derived from the combination of multiple elements in equimolar or near-equimolar ratios. The mechanical properties of HEAs are influenced by microstructural characteristics. In this study, MnCrFeCoNi HEA ribbons were produced using a technique called melt spinning, for which the wheel speed was adjusted to control the undercooling levels. The rapid solidification process under undercooling condition resulted in refined grain sizes to micrometers in the ribbons. One notable feature was the appearance of twin boundaries, which especially accounted for approximately 7.36 % of the microstructure for the ribbons produced at a wheel speed of 10 m/s. For the ribbons with thickness of micrometer scale, the mechanical properties (ultimate tensile strength up to 2.5 GPa and hardness up to 300 MPa) were analyzed by microstructure (grain boundaries and homogeneity) and exterior factors (e.g. thickness). Overall, this study provides a new approach for tailoring the microstructures and mechanical properties of HEAs via melt spinning technique. The HEA ribbons present a novel form that could potentially broaden the scope of applications for these materials.

15.
IUBMB Life ; 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38009728

ABSTRACT

Vincristine (VCR) is a microtubule-destabilizing chemotherapeutic agent commonly administered for the treatment of cancers in patients, which can induce severe side effects including neurotoxicity. In context of the effects on female fertility, ovarian toxicity has been found in patients and mice model after VCR exposure. However, the influence of VCR exposure on oocyte quality has not been elucidated. We established VCR exposure in vitro and in vivo model. The results indicated in vitro VCR exposure contributed to failure of oocyte maturation through inducing defects in spindle assembly, activation of SAC, oxidative stress, mitochondrial dysfunction, and early apoptosis, which were confirmed by using in vivo exposure model. Moreover, in vivo VCR exposure caused aneuploidy, reduced oocyte-sperm binding ability, and the number of cortical granules in mouse oocyte cortex. Taken together, this study demonstrated that VCR could cause meiotic arrest and poor quality of mouse oocyte.

16.
J Inflamm Res ; 16: 5163-5170, 2023.
Article in English | MEDLINE | ID: mdl-38026242

ABSTRACT

The ETV6::PDGFRB fusion gene is commonly reported in chronic myelomonocytic leukemia with eosinophilia, yet patients with ETV6::PDGFRB presenting myeloid and lymphoid neoplasms successively have not been reported. Here, we report the first case of a 35-year-old man with myeloid and lymphoid neoplasms harboring an ETV6::PDGFRB fusion gene who demonstrated poor response to imatinib. The patient was diagnosed with an ETV6::PDGFRB fusion gene myeloid neoplasm on initial diagnosis at our hospital. After 5 months of treatment with imatinib, he was diagnosed with T-cell lymphoblastic lymphoma. ETV6::PDGFRB turned negative after increasing the dose of imatinib, but enlarged superficial lymph nodes reappeared the following year. Notably, the patient exhibited a worse response to imatinib treatment. This study describes this rare case and speculates on a possible mechanism.

17.
Int J Mol Sci ; 24(17)2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37686249

ABSTRACT

CRISPR/Cas systems have found widespread applications in gene editing due to their high accuracy, high programmability, ease of use, and affordability. Benefiting from the cleavage properties (trans- or cis-) of Cas enzymes, the scope of CRISPR/Cas systems has expanded beyond gene editing and they have been utilized in various fields, particularly in live-cell imaging and bioanalysis. In this review, we summarize some fundamental working mechanisms and concepts of the CRISPR/Cas systems, describe the recent advances and design principles of CRISPR/Cas mediated techniques employed in live-cell imaging and bioanalysis, highlight the main applications in the imaging and biosensing of a wide range of molecular targets, and discuss the challenges and prospects of CRISPR/Cas systems in live-cell imaging and biosensing. By illustrating the imaging and bio-sensing processes, we hope this review will guide the best use of the CRISPR/Cas in imaging and quantifying biological and clinical elements and inspire new ideas for better tool design in live-cell imaging and bioanalysis.


Subject(s)
CRISPR-Cas Systems , Diagnostic Imaging , CRISPR-Cas Systems/genetics , Gene Editing
18.
Huan Jing Ke Xue ; 44(9): 5017-5024, 2023 Sep 08.
Article in Chinese | MEDLINE | ID: mdl-37699819

ABSTRACT

Antibiotic contamination in drinking water has attracted widespread attention. The pollution condition of six macrolide antibiotics (erythromycin-H2[KG-*2/5]O, clarithromycin, oleandomycin, roxithromycin, leucomycin, and tylosin) in two drinking water treatment plants was monitored, and the reaction mechanism of tylosin, a typical macrolide antibiotic, during chlorination disinfection treatment was investigated. The results showed that the six macrolide antibiotics can be widely detected in the drinking water treatment processes; however, their concentrations were generally very low. The concentrations of macrolide antibiotics in the influents and effluents ranged from 0.18 ng·L-1 to 3.97 ng·L-1 and 0.02 ng·L-1 to 1.91 ng·L-1, respectively. The removal rates of the six macrolides in the drinking water treatment were different, ranging from 18% (oleandomycin) to 100% (erythromycin- H2[KG-*2/5]O). The degradation of the six macrolides during chlorination was slow and greatly affected by water quality parameters. The chlorination degradation of tylosin followed the second-order reaction kinetic mode, with the kinetic rate constant of 0.77 L·(mol·s)-1 at pH 7.0. Nine chlorination degradation products of tylosin were detected, and the reaction pathways primarily included tertiary amine hydroxylation, aromatic oxidation, and epoxy addition.


Subject(s)
Drinking Water , Tylosin , Halogenation , Anti-Bacterial Agents , Macrolides , Erythromycin , Oleandomycin
19.
Gene ; 889: 147806, 2023 Dec 30.
Article in English | MEDLINE | ID: mdl-37717613

ABSTRACT

BACKGROUND: Various studies have highlighted the significance of miR-125b-5p in tumour chemotherapy resistance; However, whether miR-125b-5p is associated with all-trans retinoic acid (ATRA) resistance in acute promyelocytic leukemia (APL) has not been reported. METHODS: Drug-resistance-related factors in APL were predicted using the DRESIS database. The expression levels of miR-125b-5p in ATRA-sensitive and ATRA-resistant APL cells were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A nitrotetrazolium blue (NBT) reduction assay and flow cytometry (FCM) were used to detect the effect of miR-125b-5p on ATRA resistance in APL cells. An APL xenograft tumour mouse model was established to determine the effect of miR-125b-5p on ATRA resistance. A dual-luciferase gene reporter assay, qRT-PCR, and western blotting verified the regulation by miR-125b-5p of its target gene, MAPK1, and the MAPK1 downstream factor, C/EBPα. An NBT reduction assay and FCM were used to detect the effect of C/EBPα on ATRA resistance in APL cells. Western blotting and qRT-PCR were used to assess the regulation of miR-125b-5p and MAPK1 by C/EBPα. RESULTS: miR-125b-5p expression levels were dramatically increased in ATRA-resistant APL cells. Both in vitro and in vivo experiments revealed that miR-125b-5p overexpression enhanced ATRA resistance in APL. miR-125b-5p promoted ATRA resistance by sponging MAPK1. C/EBPα was negatively regulated by miR-125b-5p, which in addition, regulated ATRA resistance in APL cells. C/EBPα also regulated the miR-125b-5p-MAPK1 axis. CONCLUSION: The findings of this study indicate that the miR-125b-5p-MAPK1-C/EBPα feedback loop regulated ATRA resistance in APL. Thus, miR-125b-5p may be a promising target for treating ATRA resistance in APL.

20.
Front Med (Lausanne) ; 10: 1132695, 2023.
Article in English | MEDLINE | ID: mdl-37234246

ABSTRACT

Background: Multidrug-resistant (MDR) bacterial infection causes difficulty in the therapy of peritoneal dialysis-associated peritonitis (PDAP); however, there are few studies on multidrug-resistant organism (MDRO)-PDAP. In view of growing concerns about MDRO-PDAP, the aim of this study was to investigate the clinical features, risk factors of treatment failure, and causative pathogens of MDRO-PDAP. Methods: In total, 318 patients who underwent PD between 2013 and 2019 were included in this multicenter retrospective study. Clinical features, patient outcomes, factors related to treatment failure, and microbiological profiles associated with MDRO-PDAP were analyzed and risk factors for treatment failure associated with MDR-Escherichia coli (E. coli) were further discussed. Results: Of 1,155 peritonitis episodes, 146 eligible episodes of MDRO-PDAP, which occurred in 87 patients, were screened. There was no significant difference in the composition ratio of MDRO-PDAP between 2013-2016 and 2017-2019 (p > 0.05). E. coli was the most prevalent MDRO-PDAP isolate, with high sensitivity to meropenem (96.0%) and piperacillin/tazobactam (89.1%). Staphylococcus aureus was the second most common isolate and was susceptible to vancomycin (100%) and linezolid (100%). Compared to non-multidrug-resistant organism-PDAP, MDRO-PDAP was associated with a lower cure rate (66.4% vs. 85.5%), higher relapse rate (16.4% vs. 8.0%), and higher treatment failure rate (17.1% vs.6.5%). Dialysis age [odds ratio (OR): 1.034, 95% confidence interval (CI): 1.016-1.052, p < 0.001] and >2 previous peritonitis episodes (OR: 3.400, 95% CI: 1.014-11.400, p = 0.047) were independently associated with treatment failure. Furthermore, longer dialysis age (OR: 1.033, 95% CI: 1.003-1.064, p = 0.031) and lower blood albumin level (OR: 0.834, 95% CI: 0.700-0.993, p = 0.041) increased the risk of therapeutic failure for MDR-E. coli infection. Conclusion: The proportion of MDRO-PDAP has remained high in recent years. MDRO infection is more likely to result in worse outcomes. Dialysis age and previous multiple peritonitis infections were significantly associated with treatment failure. Treatment should be promptly individualized based on local empirical antibiotic and drug sensitivity analyses.

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