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2.
Int J Biol Macromol ; 269(Pt 2): 132128, 2024 May 07.
Article En | MEDLINE | ID: mdl-38723807

Selenium-rich tea polysaccharides (Se-TPS) were extracted via high hydrostatic pressure technology with a pressure of 400 MPa (200-500 MPa) for 10 min (3-20 min) at a material-to-solvent ratio of 1:40 (1:20-1:50). Subsequently, Se-TPS1-4 were isolated and purified, with Se-TPS3-4 as the main components. A spectral analysis proved that Se, which has antioxidant activity, existed. An in vitro study found that among Se-TPS, Se-TPS3-4 attenuated the release of ß-hexosaminidase, histamine, and interleukin (IL)-4. Furthermore, in vivo experiments revealed that treatment with Se-TPS downregulated IL-4 levels and upregulated TGF-ß and interferon-γ levels to improve imbalanced Th1/Th2 immunity in tropomyosin-sensitized mice. Moreover, Se-TPS promoted Lactobacillus and norank_f_Muribaculaceaek growth and upregulated metabolites such as genipin and coniferyl alcohol. Overall, these results showed the strong anti-allergy potential of Se-TPS by regulating mast cell-mediated allergic inflammatory responses and microbiota regulation, highlighting the potential of Se-TPS as a novel therapeutic agent to regulate allergy-associated metabolic disorders.

3.
World Allergy Organ J ; 17(5): 100887, 2024 May.
Article En | MEDLINE | ID: mdl-38742158

Objectives: To compare the epidemiology and disease patterns of allergic rhinitis (AR) at 2 different altitudes in children aged 6-7 years, and subsequently to compare with and augment data from international studies. Materials and methods: This is a multistage, clustered and stratified random sample study. The study area comprises 2 distinct areas within Yunnan Province, China. Low altitude was represented by Xishuangbanna Prefecture (XB), while high altitude was represented by Diqing Prefecture (DiQ). Each study area was subdivided into 3 sub-areas, and children aged 6-7 years were randomly sampled based on proportion-weighted sampling. The area studied includes the well-known area of Shangri-La city. Questionnaires were distributed and jointly completed by study participants and their parents or guardians, under the guidance of professional medical staff. Results: 2796 valid questionnaires out of 2933 distributed were obtained (survey response rate 95.3%). The prevalence of AR is statistically significantly higher at high altitude (DiQ, 36.0%, 95%CI 33.2-38.8) as compared to low altitude (XB, 19.7%, 95%CI 17.8-21.6) (p < 0.001). Both areas studied had a greater prevalence of AR compared to international data. In both XB and DiQ, male gender, history of early antibiotic use, urban place of birth and place of residence, presence of smokers within the same household, family history of allergic diseases (such as atopic dermatitis), as well as higher parental educational level were all associated with a higher prevalence of AR (p < 0.05). In DiQ, the prevalence of AR in Han ethnicity was greater than that of ethnic minorities (p < 0.05). In XB, being a single child was associated with an increased prevalence of AR compared to those who had siblings (p < 0.05). Conclusion: Our study found that the prevalence of AR is relatively greater at higher altitudes. Genetic and environmental factors both play an important role in the pathogenesis of AR. While altitude may be an important environmental factor, confounding factors may include humidity, temperature and distribution pattern of common aeroallergens.

4.
Oncogene ; 2024 May 02.
Article En | MEDLINE | ID: mdl-38698265

Regulatory T cells (Tregs) prevent autoimmunity and contribute to cancer progression. They exert contact-dependent inhibition of immune cells through the production of active transforming growth factor-ß1 (TGF-ß1). However, the absence of a specific surface marker makes inhibiting the production of active TGF-ß1 to specifically deplete human Tregs but not other cell types a challenge. TGF-ß1 in an inactive form binds to Tregs membrane protein Glycoprotein A Repetitions Predominant (GARP) and then activates it via an unknown mechanism. Here, we demonstrated that tumour necrosis factor receptor-associated factor 3 interacting protein 3 (TRAF3IP3) in the Treg lysosome is involved in this activation mechanism. Using a novel naphthalenelactam-platinum-based anticancer drug (NPt), we developed a new synergistic effect by suppressing ATP-binding cassette subfamily B member 9 (ABCB9) and TRAF3IP3-mediated divergent lysosomal metabolic programs in tumors and human Tregs to block the production of active GARP/TGF-ß1 for remodeling the tumor microenvironment. Mechanistically, NPt is stored in Treg lysosome to inhibit TRAF3IP3-meditated GARP/TGF-ß1 complex activation to specifically deplete Tregs. In addition, by promoting the expression of ABCB9 in lysosome membrane, NPt inhibits SARA/p-SMAD2/3 through CHRD-induced TGF-ß1 signaling pathway. In addition to expose a previously undefined divergent lysosomal metabolic program-meditated GARP/TGF-ß1 complex blockade by exploring the inherent metabolic plasticity, NPt may serve as a therapeutic tool to boost unrecognized Treg-based immune responses to infection or cancer via a mechanism distinct from traditional platinum drugs and currently available immune-modulatory antibodies.

5.
J Pharm Biomed Anal ; 245: 116183, 2024 May 03.
Article En | MEDLINE | ID: mdl-38744031

A sensitive and selective LC-MS/MS method was developed and validated for the quantitation of a novel Gαi2 inhibitor, GT-14, in rat plasma using a SCIEX 6500+ triple QUAD LC-MS system equipped with an ExionLC UHPLC unit. GT-14 (m/z 265.2 → 134.1) and griseofulvin (Internal Standard, IS) (m/z 353.1 → 285.1) were detected in a positive mode by electrospray ionization (ESI) using multiple reaction monitoring (MRM). The assay was linear in the concentration range of 0.78-1000 ng/mL in rat plasma. Both accuracy and precision values were within the acceptance criteria of ±15 %, as established by FDA guidance. The matrix effect was negligible from plasma, with signal percentages of 98.5-106.9 %. The mean recovery was 104.5 %, indicating complete extraction of GT-14 from plasma. GT-14 was found to be stable under different experimental conditions. The validated method was successfully applied to evaluate plasma protein binding and in vivo pharmacokinetics of GT-14 in rats.

6.
Front Endocrinol (Lausanne) ; 15: 1365327, 2024.
Article En | MEDLINE | ID: mdl-38737555

Endometriosis is a chronic inflammatory gynecological disease, which profoundly jeopardizes women's quality of life and places a significant medical burden on society. The pathogenesis of endometriosis remains unclear, posing major clinical challenges in diagnosis and treatment. There is an urgent demand for the development of innovative non-invasive diagnostic techniques and the identification of therapeutic targets. Extracellular vesicles, recognized for transporting a diverse array of signaling molecules, have garnered extensive attention as a novel mode of intercellular communication. A burgeoning body of research indicates that extracellular vesicles play a pivotal role in the pathogenesis of endometriosis, which may provide possibility and prospect for both diagnosis and treatment. In light of this context, this article focuses on the involvement of extracellular vesicles in the pathogenesis of endometriosis, which deliver information among endometrial stromal cells, macrophages, mesenchymal stem cells, and other cells, and explores their potential applications in the diagnosis and treatment, conducing to the emergence of new strategies for clinical diagnosis and treatment.


Endometriosis , Extracellular Vesicles , Endometriosis/pathology , Endometriosis/metabolism , Endometriosis/therapy , Endometriosis/diagnosis , Humans , Extracellular Vesicles/metabolism , Female , Endometrium/pathology , Endometrium/metabolism , Animals , Mesenchymal Stem Cells/metabolism , Cell Communication/physiology
7.
J Hazard Mater ; 472: 134496, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38718508

Effective capture of radioactive iodine from nuclear fuel reprocessing is of great importance for public safety as well as the secure utility of nuclear energy. In this work, a hydrophobic nanosheet silicalite-1 (NSL-1) zeolite with an adjustable size was developed for efficient iodine (I2) and methyl iodide (CH3I) adsorption. The optimized all-silica zeolite NSL-1 exhibits an excellent I2 uptake capacity of 553 mg/g within 45 min and a CH3I uptake capacity of 262 mg/g within 1 h. Benefiting from the reduced thickness and enhanced porosity, microporous NSL-1 possesses enhanced iodine adsorption capacity and fast adsorption kinetics, which is a considerable high value among inorganic materials. Unexpectedly, the remarkable characters of high hydrophobicity, acid-resistance and anti-oxidation endow it a higher iodine uptake capacity than traditional aluminosilicate zeolites. More importantly, the high uptake selectivity toward I2 possessed by NSL-1 owing to its hydrophobic skeleton under simulated dynamic conditions. The low cost, facile and scalable synthesis of NSL-1 further highlights great prospects for applications in the nuclear industry. This work provides useful insights for designing efficient adsorbents for iodine capture.

8.
Med Sci Monit ; 30: e942946, 2024 May 03.
Article En | MEDLINE | ID: mdl-38698627

BACKGROUND Cryopreservation preserves male fertility, crucial in oncology, advanced age, and infertility. However, it damages sperm motility, membrane, and DNA. Zinc (Zn), an antioxidant, shows promise in improving sperm quality after thawing, highlighting its potential as a cryoprotectant in reproductive medicine. MATERIAL AND METHODS Gradient concentration of ZnSO4 (0, 12.5, 25, 50, and 100 µM) was added in the Glycerol-egg yolk-citrate (GEYC) cryopreservative medium as an extender. Alterations in sperm viability and motility parameters after cryopreservation were detected in each group. Sperm plasma membrane integrity (PMI), acrosome integrity (ACR), DNA fragment index (DFI), and changes in sperm mitochondrial function were examined, including: mitochondrial potential (MMP), sperm reactive oxygen species (ROS), and sperm ATP. RESULTS We found that 50 µM ZnSO4 was the most effective for the curvilinear velocity (VCL) and the average path velocity (VAP) of sperm after cryo-resuscitation. Compared to the Zn-free group, sperm plasma membrane integrity (PMI) was increased, DNA fragmentation index (DFI) was decreased, reactive oxygen species (ROS) was reduced, and mitochondrial membrane potential (MMP) was increased after cryorevival in the presence of 50 µM ZnSO4. CONCLUSIONS Zn ion is one of the antioxidants in the cell. The results of our current clinical study are sufficient to demonstrate that Zn can improve preserves sperm quality during cryopreservation when added to GEYC. The addition of 50 µM ZnSO4 increased curve velocity, mean path velocity, sperm survival (or plasma membrane integrity), and mitochondrial membrane potential while reducing ROS production and DNA breaks compared to GEYC thawed without ZnSO4.


Cryopreservation , Cryoprotective Agents , DNA Fragmentation , Membrane Potential, Mitochondrial , Reactive Oxygen Species , Semen Preservation , Sperm Motility , Spermatozoa , Zinc , Male , Cryopreservation/methods , Humans , Spermatozoa/drug effects , Spermatozoa/metabolism , Cryoprotective Agents/pharmacology , Reactive Oxygen Species/metabolism , Sperm Motility/drug effects , Semen Preservation/methods , Membrane Potential, Mitochondrial/drug effects , DNA Fragmentation/drug effects , Zinc/pharmacology , Zinc/metabolism , Cell Membrane/drug effects , Cell Membrane/metabolism , Semen Analysis , Cell Survival/drug effects , Adult , Mitochondria/drug effects , Mitochondria/metabolism , Acrosome/drug effects , Acrosome/metabolism , Freezing
9.
J Phys Chem Lett ; : 5047-5055, 2024 May 03.
Article En | MEDLINE | ID: mdl-38701394

In this study, we analyzed the species in a model electrolyte consisting of a lithium salt, lithium bis(trifluoromethane sulfone)imide (LiTFSI), and a widely used neutral solvent propylene carbonate (PC) with excess infrared (IR) spectroscopy, ab initio molecular dynamics simulations (AIMD), and quantum chemical calculations. Complexing species including the charged ones [Li+(PC)4, TFSI-, TFSI-(PC), TFSI-(PC)2, and Li(TFSI)2-] are identified in the electrolyte. Quantum chemical calculations show strong Li+···O(PC) interaction, which suggests that Li+ would transport in the mode of solvation-carriage. However, the interaction energy of each hydrogen bond in TFSI-(PC) is very weak, suggesting that TFSI- would transport in hopping mode. In addition, the concentration dependences of the relative population of the species were also derived, providing a scenario for the dissolving process of the salt in PC. These in-depth studies provide physical insights into the structural and interactive properties of the electrolyte of lithium-ion batteries.

10.
Chemosphere ; 358: 142193, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38697562

Biochar has been utilized to reduce ciprofloxacin (CIP) residues in soil. However, little is known about the effect of biochar-derived dissolved organic matter (DOM) on residual CIP transformation. Thus, we analyzed the residual soil CIP as influenced by biochar generated from rice straw (RS3 and RS6), pig manure (PM3 and PM6), and cockroach shell (CS3 and CS6) at 300 °C and 600 °C. The three-dimensional excitation-emission matrix (3D-EEM), parallel factor analysis (PARAFAC) and two-dimensional correlation spectral analysis (2D-COS) were used to describe the potential variation in the DOM-CIP interaction. Compared with CK, biochar amendment increased the water-soluble CIP content by 160.7% (RS3), 55.2% (RS6), 534.1% (PM3), 277.5% (PM6), 1160.6% (CS3) and 703.9% (CS6), indicating that the biochar feedstock controlled the soil CIP release. The content of water-soluble CIP was positively correlated with the content of dissolved organic carbon (r = 0.922, p < 0.01) and dissolved organic nitrogen (r = 0.898, p < 0.01), suggesting that the major influence of the water-soluble CIP increase was DOM. The fluorescence quenching experiment showed that the interaction between DOM and CIP triggered static quenching and the creation of a DOM complex. The mean log K of protein-like material (4.977) was higher than that of terrestrial humus-like material (3.491), suggesting that the protein-like material complexed CIP was more stable than the humus-like material. Compared with pyrolysis at 300 °C, pyrolysis at 600 °C decreased the stability of the complex of protein-like material and CIP by 0.44 (RS), 1.689 (PM) and 0.548 (CS). This result suggested that the influence of temperature change was more profound on PM biochar-derived DOM than on RS and CS. These insights are essential for understanding CIP transportation in soil and controlling CIP contamination with biochar.

11.
J Multidiscip Healthc ; 17: 1913-1922, 2024.
Article En | MEDLINE | ID: mdl-38706505

Purpose: Clinical nursing in obstetrics and gynecology is a technically demanding job. Doctors and nurses have different professional backgrounds and work priorities, and there are differences in communication modes, which can easily lead to poor communication between medical staff and their patients. Therefore this study aims to examine the different communication roles and emphases of obstetrician and gynecologists, nurses and midwives in different sections of SEGUE framework, and further navigate the effectiveness and differences of offline and online provider-patient communication. Participants and Methods: This study employs in-depth interviews to address the research questions. A total of 24 health care providers, including 8 doctors, 5 midwives and 11 nurses, were interviewed face-to-face or by telephone. Results: Doctors pay more attention to the "giving information" stage, while nurses pay more attention to "set the stage" and "elicit information" steps. Midwives and nurses spend more time with patients before and after labor. In addition to information giving, they also accommodate the "understand the patient's perspective" and "end the encounter" steps. Nurses and midwives would attach greater importance to "understanding of patients' perspective". Online medical consultation is more convenient for patients, which can be used as a follow-up complement to offline medical consultation. Conclusion: The health care providers of different types in obstetrics and gynecology communicate collaboratively with patients, highlighting the equally important role of midwives and nurses when communicating with patients. Nurses focus on "set the stage" and "elicit information" stage. Midwife is another important information source and medical care provider, especially for pregnant women in stable conditions. Nutrition clinic of midwife could be recommended for hospitals in second- and third-tier cities, which could help to alleviate obstetricians' workload. The provision of an online collaborative consultation could be beneficial supplement after face-to-face doctor-patient communication.

13.
Mol Genet Genomics ; 299(1): 48, 2024 May 03.
Article En | MEDLINE | ID: mdl-38700639

Intramuscular fat (IMF) is a critical factor in beef quality. IMF is mainly distributed between muscle fibres and its accumulation can affect the marbling and meat quality of beef. IMF formation and deposition is a complex process and in recent years a group of non-coding RNAs (ncRNAs), known as circRNAs, have been discovered to play an important role in regulating intramuscular fat deposition. CircRNAs form a covalent loop structure after reverse splicing of precursor mRNAs. They can act by adsorbing miRNAs, thereby reducing their repressive effects on downstream target genes. Based on high-throughput sequencing of circRNAs in intramuscular fat of Qinchuan and Japanese black cattle, we identified a novel circSSBP2 that is differentially expressed between the two species and associated with adipogenesis. We show that circSSBP2 knockdown promotes bovine intramuscular preadipocyte proliferation, whereas overexpression inhibits bovine intramuscular preadipocyte proliferation. We also show that circSSBP2 can act as a molecular sponge for miR-2400 and that miR-2400 overexpression promotes bovine intramuscular preadipocyte proliferation. Furthermore, N-myc downstream-regulated gene 1 (NDRG1) was identified as a direct target gene of miR-2400, and NDRG1 interference promoted the proliferation of bovine intramuscular preadipocytes. In conclusion, our results suggest that circSSBP2 inhibits the proliferation of bovine intramuscular preadipocytes by regulating the miR-2400/NDRG1 axis.


Adipocytes , Adipogenesis , Cell Cycle Proteins , Cell Proliferation , Intracellular Signaling Peptides and Proteins , MicroRNAs , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Proliferation/genetics , Cattle , Adipocytes/metabolism , Adipocytes/cytology , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Adipogenesis/genetics , RNA, Circular/genetics , Gene Expression Regulation
14.
J Med Chem ; 2024 May 13.
Article En | MEDLINE | ID: mdl-38739678

Platinum-drug-based chemotherapy in clinics has achieved great success in clinical malignancy therapy. However, unpredictable off-target toxicity and the resulting severe side effects in the treatment are still unsolved problems. Although metabolic glycan labeling-mediated tumor-targeted therapy has been widely reported, less selective metabolic labeling in vivo limited its wide application. Herein, a novel probe of B-Ac3ManNAz that is regulated by reactive oxygen species in tumor cells is introduced to enhance the recognition and cytotoxicity of DBCO-modified oxaliplatin(IV) via bioorthogonal chemistry. B-Ac3ManNAz was synthesized from Ac4ManNAz by incorporation with 4-(hydroxymethyl) benzeneboronic acid pinacol ester (HBAPE) at the anomeric position, which is confirmed to be regulated by ROS and could robustly label glycans on the cell surface. Moreover, N3-treated tumor cells could enhance the tumor accumulation of DBCO-modified oxaliplatin(IV) via click chemistry meanwhile reduce the off-target distribution in normal tissue. Our strategy provides an effective metabolic precursor for tumor-specific labeling and targeted cancer therapies.

15.
Biochem Biophys Res Commun ; 715: 149999, 2024 Jun 30.
Article En | MEDLINE | ID: mdl-38678787

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.


Mannose , Network Pharmacology , Non-alcoholic Fatty Liver Disease , TOR Serine-Threonine Kinases , Animals , Mannose/pharmacology , Mannose/metabolism , TOR Serine-Threonine Kinases/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Mice , Male , Molecular Docking Simulation , Mice, Inbred C57BL , Signal Transduction/drug effects , Liver/metabolism , Liver/drug effects
16.
Anticancer Drugs ; 35(6): 512-524, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38602174

Repurposing existing drugs for cancer therapy has become an important strategy because of its advantages, such as cost reduction, effect and safety. The present study was designed to investigate the antimelanoma effect and possible mechanisms of action of nebivolol, which is an approved and widely prescribed antihypertensive agent. In this study, we explored the effect of nebivolol on cell proliferation and cell activity in melanoma in vitro and the potential antimelanoma mechanism of nebivolol through a series of experiments, including the analysis of the effects with regard to cell apoptosis and metastasis. Furthermore, we evaluated the antimelanoma effect on xenograft tumor models and inspected the antimelanoma mechanism of nebivolol in vivo using immunohistochemical and immunofluorescence staining assays. As results in this work, in vitro , nebivolol possessed a strong activity for suppression proliferation and cell cycle arrest on melanoma. Moreover, nebivolol significantly induced cell apoptosis in melanoma through a mitochondrial-mediated endogenous apoptosis pathway. Additionally, nebivolol inhibited melanoma cell metastasis. More importantly, nebivolol exhibited significantly effective melanoma xenograft models in vivo , which related to the mechanism of apoptosis induction, proliferation inhibition, metastasis blocking and angiogenesis arrest. Overall, the data of the present study recommend that nebivolol holds great potential in application as a novel agent for the treatment of melanoma.


Antihypertensive Agents , Apoptosis , Cell Proliferation , Melanoma , Nebivolol , Xenograft Model Antitumor Assays , Nebivolol/pharmacology , Nebivolol/therapeutic use , Animals , Humans , Melanoma/drug therapy , Melanoma/pathology , Apoptosis/drug effects , Cell Proliferation/drug effects , Mice , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Cell Line, Tumor , Mice, Nude , Cell Cycle Checkpoints/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Cell Movement/drug effects
17.
Cell Signal ; 119: 111171, 2024 Jul.
Article En | MEDLINE | ID: mdl-38604345

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease. MicroRNAs (miRNAs) are an abundant class of non-coding RNA molecules. Recent studies have shown that multiple miRNAs are abnormally expressed in patients with psoriasis. The upregulation of miR-374a-5p has been associated with psoriasis severity. However, the specific role of miR-374a-5p in the pathogenesis of psoriasis remain unclear. METHODS: qRT-PCR was employed to validate the expression of miR-374a-5p in psoriatic lesions and in a psoriasis-like cell model constructed using a mixture of M5 (IL-17A, IL-22, OSM, IL-1α, and TNF-α). HaCaT cells were transfected with miR-374a-5p mimic/inhibitor, and assays including EdU, CCK-8, and flow cytometry were conducted to evaluate the effect of miR-374a-5p on cell proliferation. The expression of inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α was verified by qRT-PCR. Bioinformatics analysis and dual-luciferase reporter gene assay were performed to detect the downstream target genes and upstream transcription factors of miR-374a-5p, followed by validation of their expression through qRT-PCR and Western blotting. A psoriasis-like mouse model was established using imiquimod cream topical application. The psoriasis area and severity index scoring, hematoxylin-eosin histology staining, and Ki67 immunohistochemistry were employed to validate the effect of miR-374a-5p on the psoriatic inflammation phenotype after intradermal injection of miR-374a-5p agomir/NC. Additionally, the expression of pathway-related molecules and inflammatory factors such as IL-1ß, IL-17a, and TNF-α was verified by immunohistochemistry. RESULTS: Upregulation of miR-374a-5p was observed in psoriatic lesions and the psoriasis-like cell model. In vitro experiments demonstrated that miR-374a-5p not only promoted the proliferation of HaCaT cells but also upregulated the expression of inflammatory cytokines, including IL-1ß, IL-6, IL-8, and TNF-α. Furthermore, miR-374a-5p promoted skin inflammation and epidermal thickening in the Imiquimod-induced psoriasis-like mouse model. Mechanistic studies revealed that miR-374a-5p led to downregulation of WIF1, thereby activating the Wnt5a/NF-κB signaling pathway. The transcription factor p65 encoded by RELA, as a subunit of NF-κB, further upregulated the expression of miR-374a-5p upon activation. This positive feedback loop promoted keratinocyte proliferation and abnormal inflammation, thereby facilitating the development of psoriasis. CONCLUSION: Our findings elucidate the role of miR-374a-5p upregulation in the pathogenesis of psoriasis through inhibition of WIF1 and activation of the Wnt5a/NF-κB pathway, providing new potential therapeutic targets for psoriasis.


Adaptor Proteins, Signal Transducing , MicroRNAs , NF-kappa B , Psoriasis , Wnt-5a Protein , Psoriasis/genetics , Psoriasis/pathology , Psoriasis/metabolism , MicroRNAs/metabolism , MicroRNAs/genetics , Humans , Wnt-5a Protein/metabolism , Wnt-5a Protein/genetics , NF-kappa B/metabolism , Animals , Mice , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Up-Regulation , Down-Regulation , Cell Proliferation , Male , HaCaT Cells , Female , Imiquimod , Adult , Repressor Proteins/metabolism , Repressor Proteins/genetics , Middle Aged
18.
Res Sq ; 2024 Mar 28.
Article En | MEDLINE | ID: mdl-38585847

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL(ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA-sequencing, and DNA methylation profiling. Whole-exome sequencing found on average 25 SNV/Indel events per sample with recurring genetic events in regulators of DNA damage (TP53, MDM4), transcription (JUNB), and epigenetic regulators (TET1, KMT2B, KMT2A, KMT2C, KMT2E). Gene expression and methylation profiling consistently subclassified ALK+ ALCLs into two groups characterized by diferential ALK expression levels. The ALK-low group showed enrichment of pathways associated with immune response, cytokine signaling, and a hypermethylated predominant pattern compared to the ALK- high group, which had more frequent copy number changes, and was enriched with pathways associated with cell growth, proliferation, metabolic pathways, and. Taken together, these findings suggest that there is molecular heterogeneity within pediatric ALK+ALCL, predicting distinct biological mechanisms that may provide novel insights into disease pathogenesis and represent prognostic markers.

19.
ACS Nano ; 18(18): 11828-11836, 2024 May 07.
Article En | MEDLINE | ID: mdl-38659192

As essential primary producers, cyanobacteria play a major role in global carbon and nitrogen cycles. Though the influence of nanoplastics on the carbon metabolism of cyanobacteria is well-studied, little is known about how nanoplastics affect their nitrogen metabolism, especially under environmentally relevant nitrogen concentrations. Here, we show that nitrogen forms regulated growth inhibition, nitrogen consumption, and the synthesis and release of microcystin (MC) in Microcystis aeruginosa exposed to 10 µg/mL amino-modified polystyrene nanoplastics (PS-NH2) with a particle size of 50 nm under environmentally relevant nitrogen concentrations of nitrate, ammonium, and urea. We demonstrate that PS-NH2 inhibit M. aeruginosa differently in nitrate, urea, and ammonium, with inhibition rates of 51.87, 39.70, and 36.69%, respectively. It is caused through the differences in impairing cell membrane integrity, disrupting redox homeostasis, and varying nitrogen transport pathways under different nitrogen forms. M. aeruginosa respond to exposure of PS-NH2 by utilizing additional nitrogen to boost the production of amino acids, thereby enhancing the synthesis of MC, extracellular polymeric substances, and membrane phospholipids. Our results found that the threat of nanoplastics on primary producers can be regulated by the nitrogen forms in freshwater ecosystems, contributing to a better understanding of nanoplastic risks under environmentally relevant conditions.


Microcystis , Nitrogen , Microcystis/drug effects , Microcystis/metabolism , Microcystis/growth & development , Nitrogen/chemistry , Nitrogen/metabolism , Microcystins/metabolism , Polystyrenes/chemistry , Particle Size , Microplastics/metabolism , Nanoparticles/chemistry , Nitrates/metabolism , Nitrates/chemistry , Urea/metabolism , Urea/chemistry , Urea/pharmacology
20.
Medicine (Baltimore) ; 103(15): e37815, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38608064

BACKGROUND: The imbalance between the generation and elimination of reactive oxygen species (ROS) is defined as oxidative stress (OS). Elevated levels of OS are implicated in various diseases, especially in gynecological and reproductive disorders. The abundance of recent literature makes it challenging to assimilate all available information. This bibliometric analysis seeks to depict the research landscape of OS in gynecological and reproductive diseases and to identify future hotspots and trends. METHODS: The Web of Science Core Collection served as the source for articles related to OS in gynecological and reproductive diseases. CtieSpace and VOSviewer software were utilized to analyzed countries/regions, institutions, journals, authors, and keywords of all eligible articles. RESULTS: A total of 1423 articles were included. There was a gradual increase in the number of publications in this field. The USA maintained the highest number of publications, with 372 articles. Cleveland Clinic was the leading institution in terms of publication volume, contributing 67 articles. In total, 6925 authors were identified. Agarwal A as the most frequently co-cited author, received 812 citations across 43 publications. The predominant clusters included "placenta," "polycystic ovary syndrome," "male infertility," and "oocyte quality." Notably, "oocyte quality'" was identified as a current key research topic. CONCLUSION: There was an uptrend in the number of articles addressing OS in gynecological and reproductive diseases. However, international collaboration and exchange were limited. The topic of male infertility had remained a consistent area of interest, and research on oocyte quality is poised to become a potential focal point in the future.


Infertility, Male , Oxidative Stress , Humans , Female , Pregnancy , Male , Reactive Oxygen Species , Bibliometrics , Ambulatory Care Facilities
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