Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 5.936
Filter
Add more filters

Complementary Medicines
Publication year range
1.
Integr Cancer Ther ; 23: 15347354241247223, 2024.
Article in English | MEDLINE | ID: mdl-38646808

ABSTRACT

BACKGROUND: Luteolin, a common dietary flavonoid found in plants, has been shown to have anti-cancer properties. However, its exact mechanisms of action in non-small cell lung cancer (NSCLC) are still not fully understood, particularly its role in regulating broader genomic networks and specific gene targets. In this study, we aimed to elucidate the role of microRNAs (miRNAs) in NSCLC treated with luteolin, using A549 cells as a model system. MATERIALS AND METHODS: miRNA profiling was conducted on luteolin-treated A549 cells using Exiqon microarrays, with validation of selected miRNAs by qRT-PCR. Bioinformatic analysis identified the regulatory roles of miRNAs in biological processes and pathways following luteolin treatment. Computational algorithms were employed to identify potential target genes. A549 cells were transfected with miR-106a-5p mimic and inhibitor or their corresponding controls. The expression levels of 2 genes, twist basic helix-loop-helix transcription factor 1 (TWIST1) and matrix metallopeptidase 2 (MMP2), and cell migration were assessed. RESULTS: miRNA profiling identified 341 miRNAs, with 18 exhibiting significantly altered expression (P < 0.05). Subsequent qRT-PCR analysis confirmed altered expression of 6 selected miRNAs. KEGG and GO analyses revealed significant alterations in pathways and biological processes crucial for tumor biology. TWIST1 and MMP2, which both contain conserved miR-106a-5p binding sites, exhibited an inverse correlation with the expression levels of miR-106a-5p. Dual-luciferase reporter assays confirmed TWIST1 and MMP2 as direct targets of miR-106a-5p. Luteolin treatment led to a reduction in A549 cell migration, and this reduction was further amplified by the overexpression of miR-106a-5p. CONCLUSION: Luteolin inhibits A549 cell migration by modulating the miRNA landscape, shedding light on its mechanisms and laying the foundation for miRNA-based therapeutic approaches for NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Cell Movement , Gene Expression Regulation, Neoplastic , Lung Neoplasms , Luteolin , Matrix Metalloproteinase 2 , MicroRNAs , Nuclear Proteins , Twist-Related Protein 1 , Up-Regulation , Humans , Luteolin/pharmacology , MicroRNAs/genetics , Lung Neoplasms/genetics , Lung Neoplasms/drug therapy , Cell Movement/drug effects , Cell Movement/genetics , Twist-Related Protein 1/genetics , Twist-Related Protein 1/metabolism , A549 Cells , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Up-Regulation/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/genetics
2.
J Ethnopharmacol ; 330: 118194, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38641077

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Prinsepia utilis Royle, native to the Himalayan region, has a long history of use in traditional medicine for its heat-clearing, detoxification, anti-inflammatory, and analgesic properties. Oils extracted from P. utilis seeds are also used in cooking and cosmetics. With the increasing market demand, this extraction process generates substantial industrial biowastes. Recent studies have found many health benefits with using aqueous extracts of these biowastes, which are also rich in polysaccharides. However, there is limited research related to the reparative effects of the water extracts of P. utilis oil cakes (WEPUOC) on disruptions of the skin barrier function. AIM OF THE STUDY: This study aimed to evaluate the reparative efficacy of WEPUOC in both acute and chronic epidermal permeability barrier disruptions. Furthermore, the study sought to explore the underlying mechanisms involved in repairing the epidermal permeability barrier. MATERIALS AND METHODS: Mouse models with induced epidermal disruptions, employing tape-stripping (TS) and acetone wiping (AC) methods, were used. The subsequent application of WEPUOC (100 mg/mL) was evaluated through various assessments, with a focus on the upregulation of mRNA and protein expression of Corneocyte Envelope (CE) related proteins, lipid synthase-associated proteins, and tight junction proteins. RESULTS: The polysaccharide was the major phytochemicals of WEPUOC and its content was determined as 32.2% by the anthranone-sulfuric acid colorimetric method. WEPUOC significantly reduced transepidermal water loss (TEWL) and improved the damaged epidermal barrier in the model group. Mechanistically, these effects were associated with heightened expression levels of key proteins such as FLG (filaggrin), INV (involucrin), LOR (loricrin), SPT, FASN, HMGCR, Claudins-1, Claudins-5, and ZO-1. CONCLUSIONS: WEPUOC, obtained from the oil cakes of P. utilis, is rich in polysaccharides and exhibits pronounced efficacy in repairing disrupted epidermal barriers through increased expression of critical proteins involved in barrier integrity. Our findings underscore the potential of P. utilis wastes in developing natural cosmetic prototypes for the treatment of diseases characterized by damaged skin barriers, including atopic dermatitis and psoriasis.


Subject(s)
Epidermis , Fatty Acid Synthases , Plant Extracts , Tight Junction Proteins , Up-Regulation , Animals , Male , Mice , Epidermis/drug effects , Epidermis/metabolism , Fatty Acid Synthases/metabolism , Fatty Acid Synthases/genetics , Permeability/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Oils/pharmacology , Plant Oils/chemistry , Tight Junction Proteins/metabolism , Up-Regulation/drug effects , Water/chemistry
3.
Tissue Cell ; 88: 102371, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38593570

ABSTRACT

BACKGROUND: Paeonol is a representative active ingredient of the traditional Chinese medicinal herbs Cortex Moutan, which has a well-established cardioprotective effect on ischemic heart disease. However, there is little evidence of the protective effect of paeonol, and its pharmacological mechanism is also unclear. This study aims to explore the protective effect and mechanism of Paeonol on myocardial infarction rat and hypoxic H9c2 cells. METHODS: Myocardial ischemia/reperfusion (I/R) was induced by occlusion of the left anterior descending coronary artery for 1 h followed by 3 h of reperfusion, and then gavage with Paeonol for 7 days. H9c2 cells were applied for the in vitro experiments and hypoxia/reoxygenation (H/R) model was established. CKIP-1 expression was evaluated by qPCR and western blot. The expression of genes involved in apoptosis, inflammation and ion channel was measured by western blot. The currents levels of Nav1.5 and Kir2.1 were measured by whole-cell patch-clamp recording. RESULTS: CKIP-1 expression was decreased in H/R-induced H9c2 cells, which was inversely increased after Paeonol treatment. Paeonol treatment could increase the viability of H/R-induced H9c2 cells and diminish the apoptosis and inflammation of H/R-induced H9c2 cells, while si-CKIP-1 treatment inhibited the phenomena. Moreover, the currents levels of Nav1.5 and Kir2.1 were reduced in H/R-induced H9c2 cells, which were inhibited after Paeonol treatment. Intragastric Paeonol can reduce the ventricular arrhythmias in rats with myocardial infarction. CONCLUSIONS: The protective effects of Paeonol on myocardial infarction rats and hypoxic H9c2 cells were achieved by up-regulating CKIP-1.


Subject(s)
Acetophenones , Cell Hypoxia , Up-Regulation , Acetophenones/pharmacology , Animals , Rats , Up-Regulation/drug effects , Cell Hypoxia/drug effects , Cell Line , Ion Channels/metabolism , Ion Channels/genetics , Apoptosis/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/drug effects , Male , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/pathology , Myocardial Infarction/metabolism , Myocardial Infarction/drug therapy , Myocardial Infarction/pathology , Rats, Sprague-Dawley
4.
J Med Food ; 27(7): 661-668, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38603571

ABSTRACT

We investigated the effects of Lactuca sativa L. extracts (Lactuc) on pentobarbital-induced sleep in mice to elucidate the mechanisms underlying its impact on sleep quality. Mice were randomly assigned to five groups: control, positive control (diazepam 2 mg/kg b.w.), and three groups orally administered with Lactuc (50, 100, and 200 mg/kg b.w.). After 2 weeks of oral administration and intraperitoneal injections, the mice were killed. We found that the Lactuc-administered groups had significantly reduced sleep latency and increased sleep duration compared with the control group. Furthermore, the oral administration of Lactuc induced a significant increase in mRNA expression and protein expression of adenosine A1 receptor in the brains compared with the expressions in the control group. In addition, the Lactuc-administered groups exhibited significantly higher levels of mRNA expressions of GABAA receptors subunits α2, ß2, γ1, and, γ2 in the brain tissue. Therefore, we suggest that Lactuc could be used to develop natural products that effectively improve sleep quality and duration.


Subject(s)
Lactuca , Pentobarbital , Plant Extracts , Receptor, Adenosine A1 , Receptors, GABA-A , Sleep , Up-Regulation , Animals , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Pentobarbital/pharmacology , Mice , Receptors, GABA-A/metabolism , Receptors, GABA-A/genetics , Sleep/drug effects , Male , Receptor, Adenosine A1/metabolism , Receptor, Adenosine A1/genetics , Up-Regulation/drug effects , Lactuca/chemistry , Lactuca/metabolism , Brain/metabolism , Brain/drug effects , Humans , Mice, Inbred ICR , Sleep Duration
5.
Int J Mol Sci ; 25(7)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38612656

ABSTRACT

There is no mouse model of patellar tendinopathy. This study aimed to establish a mouse inflammatory and degenerative patellar tendon injury model, which will facilitate research on patellar tendinopathy using advanced molecular tools including transgenic models. Collagenase at different doses (low dose (LD), medium dose (MD), high dose (HD)) or saline was injected over the mouse patellar tendon. At weeks 1, 2, 4, and 8 post-injection, the tendons were harvested for histology and further examined by micro-computed tomography (microCT) imaging at week 8. The optimal dose group and the saline group were further evaluated by immunohistochemical staining, gait pattern, and biomechanical properties. The histopathological score increased dose-dependently post-collagenase injection. Ectopic mineralization was observed and increased with collagenase dose. The LD group was selected for further analysis. The expression of IL-10, TNF-α, and MMP-1 significantly increased post-injection. The changes of limb idleness index (ΔLII) compared to preinjury state were significantly higher, while the ultimate load, stiffness, ultimate stress, and maximum Young's modulus were significantly lower in the LD group compared to the saline group. A mouse inflammatory degenerative model of patellar tendon injury resembling tendinopathy was established as indicated by the dose-dependent increase in tendon histopathology, ectopic calcification, decrease in biomechanical properties, and pain-associated gait changes.


Subject(s)
Musculoskeletal Diseases , Tendinopathy , Tendon Injuries , Animals , Mice , Up-Regulation , X-Ray Microtomography , Inflammation , Disease Models, Animal
6.
Behav Res Ther ; 176: 104523, 2024 05.
Article in English | MEDLINE | ID: mdl-38513424

ABSTRACT

Previous work has shown that adults suffering from major depressive disorder (MDD) can increase their amygdala reactivity while recalling positive memories via real-time neurofeedback (rt-fMRI-nf) training, which is associated with reduction in depressive symptoms. This study investigated if this intervention could also be considered for patients suffering from MDD who do not respond to standard psychological and pharmacological interventions, i.e., treatment resistant (TR-MDD). 15 participants received 5 neurofeedback sessions. Outcome measures were depressive symptoms assessed by BDI scores up to 12 weeks following acute intervention, and amygdala activity changes from initial baseline to final transfer run during neurofeedback sessions (neurofeedback success). Participants succeeded in increasing their amygdala activity. A main effect of visit on BDI scores indicated a significant reduction in depressive symptomatology. Percent signal change in the amygdala showed a learning curve during the first session only. Neurofeedback success computed by session was significantly positive only during the second session. When examining the baseline amygdala response, baseline activity stabilized/asymptoted by session 3. This proof-of-concept study suggests that only two neurofeedback sessions are necessary to enable those patients to upregulate their amygdala activity, warranting a future RCT. Over the course of the rtfMRI-nf intervention, participants also reported reduced depressive symptomatology. Clinical trial registration number: NCT03428828 on ClinicalTrials.gov.


Subject(s)
Depressive Disorder, Major , Depressive Disorder, Treatment-Resistant , Neurofeedback , Adult , Humans , Amygdala/physiology , Depressive Disorder, Major/therapy , Depressive Disorder, Treatment-Resistant/therapy , Magnetic Resonance Imaging , Neurofeedback/physiology , Up-Regulation
7.
Phytomedicine ; 128: 155547, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38547615

ABSTRACT

BACKGROUND: Emerging evidence suggests that pyroptosis, a form of programmed cell death, has been implicated in cancer progression. The involvement of specific proteins in pyroptosis is an area of growing interest. TOM20, an outer mitochondrial membrane protein, has recently garnered attention for its potential role in pyroptosis. Our previous study found that NBT could induce pyroptosis by ROS/JNK pathway in esophageal cancer cells. PURPOSE: This study aims to investigate whether NBT induces pyroptosis and verify whether such effects are involved in up-regulation of TOM20 in esophageal cancer cells. METHODS: The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) was used to analyze the clinical significance of GSDME in esophageal cancer. MTT assay, morphological observation and Western blot were performed to verify the roles of TOM20 and BAX in NBT-induced pyroptosis after CRISPR-Cas9-mediated knockout. Immunofluorescence was used to determine the subcellular locations of BAX and cytochrome c. MitoSOX Red was employed to assess the mitochondrial reactive oxygen species (ROS) level. KYSE450 and TOM20 knockout KYSE450-/- xenograft models were established to elucidate the mechanisms involved in NBT-induced cell death. RESULTS: In this study, NBT effectively upregulated the expression of TOM20 and facilitated the translocation of BAX to mitochondria, which promoted the release of cytochrome c from mitochondria to the cytoplasm, leading to the activation of caspase-9 and caspase-3, and finally induced pyroptosis. Knocking out TOM20 by CRISPR-Cas9 significantly inhibited the expression of BAX and the downstream BAX/caspase-3/GSDME pathway, which attenuated NBT-induced pyroptosis. The elevated mitochondrial ROS level was observed after NBT treatment. Remarkably, the inhibition of ROS by N-acetylcysteine (NAC) effectively suppressed the activation of TOM20/BAX pathway. Moreover, in vivo experiments demonstrated that NBT exhibited potent antitumor effects in both KYSE450 and TOM20 knockout KYSE450-/- xenograft models. Notably, the attenuated antitumor effects and reduced cleavage of GSDME were observed in the TOM20 knockout model. CONCLUSION: These findings reveal that NBT induces pyroptosis through ROS/TOM20/BAX/GSDME pathway, which highlight the therapeutic potential of targeting TOM20 and GSDME, providing promising prospects for the development of innovative and effective treatment approaches for esophageal cancer.


Subject(s)
Esophageal Neoplasms , Gasdermins , Mitochondrial Precursor Protein Import Complex Proteins , Pyroptosis , Reactive Oxygen Species , Signal Transduction , bcl-2-Associated X Protein , Animals , Humans , Male , Mice , bcl-2-Associated X Protein/metabolism , Caspase 3/metabolism , Cell Line, Tumor , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/metabolism , Mice, Nude , Mitochondria/drug effects , Mitochondria/metabolism , Phosphate-Binding Proteins/metabolism , Pyroptosis/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Up-Regulation/drug effects
8.
Nutr Res ; 125: 16-26, 2024 May.
Article in English | MEDLINE | ID: mdl-38432179

ABSTRACT

Depression and anxiety disorders are among the most common mental health disorders that affect US adults today, frequently related to vitamin D (VD) insufficiency. Along with VD, growing evidence suggests gut microbiota likely play a role in neuropsychiatric disorders. Here, we investigated if modulation of gut microbiota would disrupt host VD status and promote behaviors related to depression and anxiety in adult mice. Six-week-old male and female C57BL/6J mice (n = 10/mice/group) were randomly assigned to receive (1) control diet (CTR), control diet treated with antibiotics (AB), control diet with total 5000 IU of VD (VD), VD treated with antibiotics (VD + AB), VD supplemented with 5% w/w fructooligosaccharides (FOS; VF), and VF diet treated with antibiotics (VF + AB), respectively, for 8 weeks. Our study demonstrated that VD status was not affected by antibiotic regimen. VD alone ameliorates anxiety-related behavior in female mice, and that combination with FOS (i.e., VF) did not further improve the outcome. Male mice, in contrast, exhibit greater anxiety with VF, but not VD, when compared with CTR mice. Colonic VD receptor was elevated in VF-treated mice in both sexes, compared with CTR, which was positively correlated to colonic TPH1, a rate-limiting enzyme for serotonin synthesis. Taken together, our data indicate that the effect of VF on anxiety-related behavior is sex-specific, which may partially be attributed to the activation of colonic VD signaling and subsequent serotonin synthesis. The synergistic or additive effect of VD and FOS on mood disorders remained to be investigated.


Subject(s)
Anxiety , Behavior, Animal , Cholecalciferol , Colon , Gastrointestinal Microbiome , Mice, Inbred C57BL , Oligosaccharides , Receptors, Calcitriol , Animals , Oligosaccharides/pharmacology , Male , Female , Anxiety/drug therapy , Receptors, Calcitriol/metabolism , Gastrointestinal Microbiome/drug effects , Colon/metabolism , Colon/drug effects , Behavior, Animal/drug effects , Cholecalciferol/pharmacology , Mice , Up-Regulation , Sex Factors , Dietary Supplements , Anti-Bacterial Agents/pharmacology , Depression/drug therapy
9.
Front Cell Infect Microbiol ; 14: 1332381, 2024.
Article in English | MEDLINE | ID: mdl-38357442

ABSTRACT

Visceral leishmaniasis (VL) is the most severe type of leishmaniasis which is caused by infection of Leishmania donovani complex. In the BALB/c mouse model of VL, multinucleated giant cells (MGCs) with heavy parasite infection consist of the largest population of hemophagocytes in the spleen of L. donovani-infected mice, indicating that MGCs provide the parasites a circumstance beneficial for their survival. Although ATP6V0D2 is a demonstrated factor inducing the formation of hemophagocytic MGCs during L. donovani infection, functions of this protein in shaping the infection outcome in macrophages remain unclear. Here we evaluated the influence of upregulated ATP6V0D2 on intracellular survival of the parasites. L. donovani infection-induced hemophagocytosis of normal erythrocytes by macrophages was suppressed by RNAi-based knockdown of Atp6v0d2. The knockdown of Atp6v0d2 did not improve the survival of amastigotes within macrophages when the cells were cultured in the absence of erythrocytes. On the other hand, reduced intracellular survival of amastigotes in macrophages by the knockdown was observed when macrophages were supplemented with antibody-opsonized erythrocytes before infection. There, increase in cytosolic labile iron pool was observed in the L. donovani-infected knocked-down macrophages. It suggests that ATP6V0D2 plays roles not only in upregulation of hemophagocytosis but also in iron trafficking within L. donovani-infected macrophages. Superior access to iron in macrophages may be how the upregulated expression of the molecule brings benefit to Leishmania for their intracellular survival in the presence of erythrocytes.


Subject(s)
Leishmania donovani , Leishmaniasis, Visceral , Animals , Mice , Erythrocytes , Iron/metabolism , Leishmaniasis, Visceral/parasitology , Macrophages/metabolism , Mice, Inbred BALB C , Up-Regulation
10.
Int Immunopharmacol ; 129: 111607, 2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38330798

ABSTRACT

Novel allergen immunotherapy (AIT) approaches necessitate the use of more effective and safe therapeutics, which can be accomplished by employing novel adjuvants for improved innate immune cell activation, as well as hypoallergenic allergen forms. In this study, we investigate the immunomodulatory effects of a chimera rBet v 1a-BanLecwt (rBv1a-BLwt; Cwt) composed of the major birch pollen allergen Bet v 1a and banana lectin (BanLecwt; BLwt) and two novel chimeras, rBv1l-BLH84T (rBet v 1l-BanLecH84T; C1) and rBLH84T-Bv1l (rBanLecH84T-Bet v 1l; C2), both composed of BLH84T and hypoallergenic birch pollen allergen Bv1l in the co-culture model Caco-2/THP-1, and PBMCs from donors with birch pollen allergy. The chimeric molecules rBv1l-BLH84T (C1) and rBLH84T-Bv1l (C2) were created in silico and then produced in E. coli using recombinant DNA technology. Real-time PCR analysis of gene expression following compound treatment in the co-culture model revealed that all three chimeras have the potential to induce the anti-inflammatory cytokine IL-10 gene expression in Caco-2 cells and IFN-γ gene expression in THP-1 cells. Sandwich ELISA revealed that Cwt increased IL-10 secretion and IFN-/IL-4 levels in PBMCs from birch pollen allergic donors, whereas C1 and C2 were less effective. The findings suggest that Cwt should be analyzed further due to its potential benefit in AIT.


Subject(s)
Betula , Hypersensitivity , Humans , Betula/genetics , Caco-2 Cells , Interleukin-4/genetics , Pollen , Interleukin-10/genetics , Coculture Techniques , Up-Regulation , Escherichia coli/genetics , Plant Proteins/genetics , Antigens, Plant/genetics , Allergens/genetics , Gene Expression , Recombinant Proteins
11.
Clin Exp Pharmacol Physiol ; 51(4): e13844, 2024 04.
Article in English | MEDLINE | ID: mdl-38350599

ABSTRACT

Botulinum neurotoxin A (BoNT) is being shown to have anticancer action as a potential adjuvant treatment. The transient receptor potential (TRP) melastatin 2 (TRPM2) stimulator action of BoNT was reported in glioblastoma cells, but not in colorectal cancer (HT29) cells. By activating TRPM2, we evaluated the impacts of BoNT and oxaliplatin (OXA) incubations on oxidant and apoptotic values within the HT29 cells. Control, BoNT (5 IU for 24 h), OXA (50 µM for 24 h) and their combinations were induced. We found that TRPM2 protein is upregulated and mediates enhanced BoNT and OXA-induced Ca2+ entry in cells as compared to control cells. The increase of free reactive oxygen species (ROS), but the decrease of glutathione is the main ROS responsible for TRPM2 activation on H29 exposure to oxidative stress. BoNT and OXA-mediated Ca2+ entry through TRPM2 stimulation in response to H2 O2 results in mitochondrial Ca2+ overload, followed by mitochondrial membrane depolarization, apoptosis and caspase-3/-8/-9, although they were diminished in the TRPM2 antagonist groups (N-(p-amylcinnamoyl)anthranilic acid and carvacrol). In conclusion, by increasing the susceptibility of HT29 tumour cells to oxidative stress and apoptosis, the combined administration of BoNT and OXA via the targeting of TRPM2 may offer a different approach to kill the tumour cells.


Subject(s)
Botulinum Toxins, Type A , Colorectal Neoplasms , TRPM Cation Channels , Humans , Oxaliplatin/pharmacology , Reactive Oxygen Species/metabolism , Botulinum Toxins, Type A/metabolism , Up-Regulation , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolism , Cell Death , Oxidative Stress/physiology , Apoptosis/physiology , Colorectal Neoplasms/drug therapy , Calcium/metabolism
12.
Neuropsychologia ; 195: 108804, 2024 03 12.
Article in English | MEDLINE | ID: mdl-38242318

ABSTRACT

As a fundamental attention function, sustained attention plays a critical role in general cognitive abilities and is closely linked to EEG alpha oscillations. Neurofeedback training (NFT) of alpha activity on different aspects of attention has been studied previously. However, it remains unclear how NFT with up- or down-regulation directions modulates sustained attention. Here we employed a counterbalanced single-blind sham-controlled crossover design, in which healthy young adults underwent one NFT session of alpha up-regulation, one NFT session of alpha down-regulation, and one sham-control NFT session over the posterior area. The session order was counterbalanced with a 7-day interval between each session. After each NFT session, the participants completed a visual continuous temporal expectancy task (vCTET) to assess their sustained attention performance. The results showed that compared to sham-control NFT, successful learning of alpha up-regulation resulted in increased reaction time at the beginning of the attention task but a slower increase over vCTET blocks. On the other hand, successful learning of alpha down-regulation had no impact on attention performance compared to sham-control NFT. These findings suggest that successful learning of alpha up-regulation through NFT could impair initial attention performance but slow down visual attention deterioration over time, i.e., alpha enhancement by NFT stabilizing visual attention.


Subject(s)
Neurofeedback , Young Adult , Humans , Neurofeedback/methods , Electroencephalography , Single-Blind Method , Up-Regulation , Learning
13.
J Leukoc Biol ; 116(1): 6-17, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38289835

ABSTRACT

The mechanisms driving metabolic reprogramming during B cell activation are unclear, particularly roles for enzymatic pathways involved in lipid remodeling. We found that murine B cell activation with lipopolysaccharide (LPS) led to a 1.6-fold increase in total lipids that included higher levels of phosphatidylethanolamine (PE) and plasmenyl PE. Selenoprotein I (SELENOI) is an ethanolamine phospholipid transferase involved in the synthesis of both PE and plasmenyl PE, and SELENOI expression was also upregulated during activation. Selenoi knockout (KO) B cells exhibited decreased levels of plasmenyl PE, which plays an important antioxidant role. Lipid peroxidation was measured and found to increase ∼2-fold in KO vs. wild-type (WT) B cells. Cell death was not impacted by KO in LPS-treated B cells and proliferation was only slightly reduced, but differentiation into CD138 + Blimp-1+ plasma B cells was decreased ∼2-fold. This led to examination of B cell receptors important for differentiation that recognize the ligand B cell activating factor, and levels of TACI (transmembrane activator, calcium-modulator, and cytophilin ligand interactor) (CD267) were significantly decreased on KO B cells compared with WT control cells. Vaccination with ovalbumin/adjuvant led to decreased ovalbumin-specific immunoglobulin M (IgM) levels in sera of KO mice compared with WT mice. Real-time polymerase chain reaction analyses revealed a decreased switch from surface to secreted IgM in spleens of KO mice induced by vaccination or LP-BM5 retrovirus infection. Overall, these findings detail the lipidomic response of B cells to LPS activation and reveal the importance of upregulated SELENOI for promoting differentiation into IgM-secreting plasma B cells.


Subject(s)
B-Lymphocytes , Cell Differentiation , Immunoglobulin M , Lipopolysaccharides , Lymphocyte Activation , Selenoproteins , Animals , Lipopolysaccharides/pharmacology , Immunoglobulin M/blood , Immunoglobulin M/metabolism , Mice , Selenoproteins/metabolism , Selenoproteins/genetics , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Mice, Knockout , Plasma Cells/metabolism , Plasma Cells/immunology , Lipidomics , Up-Regulation , Mice, Inbred C57BL
14.
Protoplasma ; 261(4): 735-747, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38291258

ABSTRACT

Drought stress is one of the major limiting factors for the production of tomato in Iran. In this study, the efficiency of selenate and Se nanoparticle (SeNP) foliar application on tomato plants was assessed to vestigate mitigating the risk associated with water-deficit conditions. Tomato plants were treated with SeNPs at the concentrations of 0 and 4 mg L-1; after the third sprays, the plants were exposed to water-deficit conditions. The foliar spraying with SeNPs not only improved growth, yield, and developmental switch to the flowering phase but also noticeably mitigated the detrimental risk associated with the water-deficit conditions. Gene expression experiments showed a slight increase in expression of microRNA-172 (miR-172) in the SeNP-treated plants in normal irrigation, whereas miR-172 displayed a downregulation trend in response to drought stress. The bZIP transcription factor and CRTISO genes were upregulated following the SeNP and drought treatments. Drought stress significantly increased the H2O2 accumulation that is mitigated with SeNPs. The foliar spraying with Se or SeNPs shared a similar trend to alleviate the negative effect of drought stress on the membrane integrity. The applied supplements also conferred drought tolerance through noticeable improvements in the non-enzymatic (ascorbate and glutathione) and enzymatic (catalase and peroxidase) antioxidants. The SeNP-mediated improvement in drought stress tolerance correlated significantly with increases in the activity of phenylalanine ammonia-lyase, proline, non-protein thiols, and flavonoid concentrations. SeNPs also improved the fruit quality regarding K, Mg, Fe, and Se concentrations. It was concluded that foliar spraying with SeNPs could mitigate the detrimental risk associated with the water-deficit conditions.


Subject(s)
Antioxidants , Droughts , MicroRNAs , Selenium , Solanum lycopersicum , Solanum lycopersicum/genetics , Solanum lycopersicum/drug effects , MicroRNAs/genetics , Selenium/pharmacology , Antioxidants/metabolism , Nanoparticles/chemistry , Secondary Metabolism/drug effects , Secondary Metabolism/genetics , Gene Expression Regulation, Plant/drug effects , Up-Regulation/drug effects , Plant Proteins/genetics , Plant Proteins/metabolism , Drought Resistance
15.
Cancer Lett ; 583: 216652, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38242196

ABSTRACT

Systemic iron overload is a common clinical challenge leading to significantly serious complications in patients with acute myeloid leukemia (AML), which affects both the quality of life and the overall survival of patients. Symptoms can be relieved after iron chelation therapy in clinical practice. However, the roles and mechanisms of iron overload on the initiation and progression of leukemia remain elusive. Here we studied the correlation between iron overload and AML clinical outcome, and further explored the role and pathophysiologic mechanism of iron overload in AML by using two mouse models: an iron overload MLL-AF9-induced AML mouse model and a nude xenograft mouse model. Patients with AML had an increased ferritin level, particularly in the myelomonocytic (M4) or monocytic (M5) subtypes. High level of iron expression correlated with a worsened prognosis in AML patients and a shortened survival time in AML mice. Furthermore, iron overload increased the tumor load in the bone marrow (BM) and extramedullary tissues by promoting the proliferation of leukemia cells through the upregulation of FOS. Collectively, our findings provide new insights into the roles of iron overload in AML. Additionally, this study may provide a potential therapeutic target to improve the outcome of AML patients and a rationale for the prospective evaluation of iron chelation therapy in AML.


Subject(s)
Iron Overload , Leukemia, Myeloid, Acute , Humans , Animals , Mice , Up-Regulation , Quality of Life , Leukemia, Myeloid, Acute/genetics , Iron/metabolism , Myeloid-Lymphoid Leukemia Protein/genetics , Myeloid-Lymphoid Leukemia Protein/metabolism , Oncogene Proteins, Fusion/genetics
16.
J Ethnopharmacol ; 324: 117734, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38237645

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Fangji Huangqi Decoction (FJHQ), a traditional Chinese medicinal formula outlined in Zhang Zhongjing's "Jin Gui Yao Lue" during the Han Dynasty, is often used to treat conditions characterized by symptoms like edema and dysuria, including membranous nephropathy (MN). Despite its proven clinical effectiveness, the exact mechanisms through which FJHQ acts on MN remain elusive. AIM OF THE STUDY: This study aimed to investigate whether FJHQ enhances BNIP3-mediated mitophagy in podocytes by promoting BNIP3 expression and whether this improvement leads to the amelioration of MN. MATERIALS AND METHODS: In this study, by establishing passive Heymann nephritis (PHN) rats, an experimental rat model of MN induced by sheep anti-rat Fx1A serum, we evaluated the effects of FJHQ in vivo. In vitro experiments were carried out by treating primary podocytes with experimental rat serum. Furthermore, the potential mechanism by which FJHQ acts through BNIP3 was further examined by transfecting primary podocytes with the siRNA of BNIP3 or the corresponding control vector. RESULTS: After 4 weeks, significant kidney damage was observed in the rats in the model group, comparatively, FJHQ markedly decreased urine volume, 24-h urinary protein, blood urea nitrogen (BUN), creatinine (Scr), and increased serum total albumin (ALB). Histology showed that FJHQ caused significant improvements in glomerular hyperplasia, and IgG immune complex deposition in MN rats. JC-1 fluorescence labelling and flow cytometry analysis showed that FJHQ could significantly increase mitochondrial membrane potential in vivo. In the mitochondria of MN model rats, FJHQ was able to down-regulate the expression of P62 and up-regulate the expression of BNIP3, LC3B, and LC3 II/LC3 I, according to Western blot and immunofluorescence studies. Furthermore, FJHQ has been shown to significantly up-regulate mitochondrial membrane potential, down-regulate P62 expression in mitochondria, and up-regulate the expression of BNIP3, LC3B, and LC3 II/LC3 I in mitochondria at the cellular level. After the administration of the autophagy inhibitor chloroquine, the serum of rats treated with FJHQ further increased the expression of LC3 II/LC3 I in primary podocytes, showing higher autophagy flow. After the interference of BNIP3 in podocytes, the effect of FJHQ on mitochondrial membrane potential and autophagy-related proteins almost disappeared. CONCLUSION: FJHQ enhanced mitophagy in podocytes by promoting the expression of BNIP3, thereby contributing to the amelioration of MN. This work reveals the possible underlying mechanism by which FJHQ improves MN and provides a new avenue for MN treatment.


Subject(s)
Drugs, Chinese Herbal , Glomerulonephritis, Membranous , Kidney Diseases , Rats , Animals , Sheep , Glomerulonephritis, Membranous/drug therapy , Glomerulonephritis, Membranous/pathology , Mitophagy/genetics , Up-Regulation , Kidney Glomerulus/pathology , Membrane Proteins/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism
17.
PLoS One ; 19(1): e0296024, 2024.
Article in English | MEDLINE | ID: mdl-38206981

ABSTRACT

Chronic inflammatory enteropathy (CIE) in dogs, a spontaneous model of human inflammatory bowel disease (IBD), is associated with a high rate of cobalamin deficiency. The etiology of hypocobalaminemia in human IBD and canine CIE remains unknown, and compromised intestinal uptake of cobalamin resulting from ileal cobalamin receptor deficiency has been proposed as a possible cause. Here, we evaluated the intestinal expression of the cobalamin receptor subunits, amnionless (AMN) and cubilin (CUBN), and the basolateral efflux transporter multi-drug resistance protein 1 (MRP1) in 22 dogs with CIE in comparison to healthy dogs. Epithelial CUBN and AMN levels were quantified by confocal laser scanning microscopy using immunohistochemistry in endoscopic ileal biopsies from dogs with (i) CIE and normocobalaminemia, (ii) CIE and suboptimal serum cobalamin status, (iii) CIE and severe hypocobalaminemia, and (iv) healthy controls. CUBN and MRP1 expression was quantified by RT-qPCR. Receptor expression was evaluated for correlation with clinical patient data. Ileal mucosal protein levels of AMN and CUBN as well as mRNA levels of CUBN and MRP1 were significantly increased in dogs with CIE compared to healthy controls. Ileal cobalamin receptor expression was positively correlated with age, clinical disease activity index (CCECAI) score, and lacteal dilation in the ileum, inversely correlated with serum folate concentrations, but was not associated with serum cobalamin concentrations. Cobalamin receptor downregulation does not appear to be the primary cause of hypocobalaminemia in canine CIE. In dogs of older age with severe clinical signs and/or microscopic intestinal lesions, intestinal cobalamin receptor upregulation is proposed as a mechanism to compensate for CIE-associated hypocobalaminemia. These results support oral supplementation strategies in hypocobalaminemic CIE patients.


Subject(s)
Dog Diseases , Inflammatory Bowel Diseases , Multidrug Resistance-Associated Proteins , Vitamin B 12 Deficiency , Humans , Dogs , Animals , Vitamin B 12 , Up-Regulation , Vitamin B 12 Deficiency/genetics , Vitamin B 12 Deficiency/veterinary , Inflammatory Bowel Diseases/pathology , Ileum/metabolism , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Dog Diseases/genetics
18.
J Cell Mol Med ; 28(1): e18026, 2024 01.
Article in English | MEDLINE | ID: mdl-37961985

ABSTRACT

In the previous study, we found that the oral sodium valproate (SVP) increased the relative abundance of Akkermansia muciniphila (A. muciniphila) in rats, and plasma aspartate transaminase (AST) and alanine aminotransferase (ALT) activities were positively correlated with A. muciniphila levels. This study aimed to further investigate the role of A. muciniphila in SVP-induced hepatotoxicity by orally supplementing rats with the representative strain of A. muciniphila, A. muciniphila MucT. Additionally, the fresh faeces were incubated anaerobically with SVP to investigate the effect of SVP on faecal A. muciniphila in the absence of host influence. Results showed that A. muciniphila MucT ameliorated the hepatotoxicity and upregulation of A. muciniphila induced by SVP. SVP also induced a noteworthy elevation of A. muciniphila level in vitro, supporting the observation in vivo. Therefore, we speculate that A. muciniphila MucT may be a potential therapeutic strategy for SVP-induced hepatotoxicity. In addition, the increased A. muciniphila induced by SVP may differ from A. muciniphila MucT, but further evidence is needed. These findings provide new insights into the relationships between A. muciniphila and SVP-induced hepatotoxicity, highlighting the potential for different A. muciniphila strains to have distinct or even opposing effects on SVP-induced hepatotoxicity.


Subject(s)
Chemical and Drug Induced Liver Injury , Valproic Acid , Rats , Animals , Up-Regulation , Verrucomicrobia/physiology , Akkermansia
19.
J Nat Med ; 78(1): 208-215, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38063995

ABSTRACT

Recently, the number of patients diagnosed with dementia has increased. The World Health Organization (WHO) estimates that 50 million patients suffer from dementia. Although several therapeutic strategies have been proposed, currently, there is no curative approach for treating dementia. Neurodegeneration is an irreversible process. As this disease gradually progresses over 15-20 years, a low-cost and sustainable method for preventing these diseases is desired. Cacao nib is consumed in many countries, and a recent clinical study indicated that cocoa intake upregulates brain-derived neurotrophic factor (BDNF), which plays a significant role in memory formation and neuronal cell survival. In the present study, neural cells were treated with cacao nib extract or the 17 characteristic components of cacao nib. Treatment with Cacao nib extract upregulates BDNF mRNA expression. In addition, cacao nib extract elicits the phosphorylation of cAMP-response-element-binding protein (CREB), which regulates the transcription of BDNF. Among the 17 species screened, isovaleraldehyde (IVA), also known as an aroma component of cacao nibs extract, improved BDNF mRNA expression without SH-SY5Y cell toxicity. IVA also promoted CREB phosphorylation through a cAMP-dependent protein kinase (PKA)-dependent mechanism. In conclusion, IVA could be responsible for the BDNF upregulation effect of cacao nib, and IVA upregulated BDNF expression via the PKA-CREB axis.


Subject(s)
Aldehydes , Brain-Derived Neurotrophic Factor , Cyclic AMP Response Element-Binding Protein , Neuroprotective Agents , Up-Regulation , Neuroprotective Agents/pharmacology , Aldehydes/pharmacology , Up-Regulation/drug effects , Brain-Derived Neurotrophic Factor/genetics , Humans , Cell Line, Tumor , Cacao/chemistry , Plant Extracts/pharmacology , Cyclic AMP-Dependent Protein Kinases/metabolism , Signal Transduction/drug effects , Enzyme Activation/drug effects , Cyclic AMP Response Element-Binding Protein/metabolism
20.
J Nat Med ; 78(2): 285-295, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38082192

ABSTRACT

The natural product Honokiol exhibits robust antitumor activity against a range of cancers, and it has also received approval to undergo phase I clinical trial testing. We confrmed that honokiol can promote the apoptotic death of tumor cells through cell experiments. Then siRNA constructs specific for PIAS3, PIAS3 overexpression plasmid and the mutation of the STAT3 Tyr705 residue were used to confirm the mechanism of Honokiol-induced apoptosis. Finally, we confrmed that honokiol can promote PIAS3 upregulation, in turn suppressing STAT3 Tyr705 phosphorylation through the in vivo and in vitro experiments. Honokiol was ultimately found to reduce tumor cell viability by promoting apoptosis through a mechanism dependent on the ability of Honokiol to promote PIAS3 upregulation and the selective inhibition of p-STAT3 (Tyr705) without affecting p-STAT3 (Ser727) or p-STAT1 (Tyr701) levels. PIAS3 knockdown and overexpression in tumor cells altered STAT3 activation and associated DNA binding activity through the control of Tyr705 phosphorylation via PIAS3-STAT3 complex formation, ultimately shaping Honokiol-induced tumor cell apoptosis. Honokiol was also confirmed to significantly prolong the survival of mice bearing xenograft tumors in a PIAS3-dependent fashion. Together, these findings highlight a novel pathway through which Honokiol can promote PIAS3 upregulation, in turn suppressing STAT3 Tyr705 phosphorylation and promoting the apoptotic death of tumor cells.


Subject(s)
Allyl Compounds , Apoptosis , Biphenyl Compounds , Phenols , Tyrosine , Humans , Animals , Mice , Phosphorylation , Up-Regulation , Cell Line, Tumor , Molecular Chaperones/genetics , Molecular Chaperones/metabolism , Protein Inhibitors of Activated STAT/genetics , Protein Inhibitors of Activated STAT/metabolism , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL