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1.
Clin Cosmet Investig Dermatol ; 17: 1527-1541, 2024.
Article in English | MEDLINE | ID: mdl-38948922

ABSTRACT

Purpose: This study seeks to investigate the effect of evodiamine on psoriasis and psoriatic pruritus. Methods: Imiquimod-induced psoriasiform dermatitis in mice was used as a model, and evodiamine was topically applied for seven days. The mice were observed daily for skin damage on the back, clinical score and their scratching behavior was recorded. Blood samples were collected on the final day of the experiment, and the serum levels of pruritus-associated inflammatory cytokines tumor necrosis factor (TNF) -α, interleukin (IL) -23, and IL-17A were measured using enzyme-linked immunosorbent assay. Histopathological changes were observed in Hematoxylin and Eosin-stained skin specimens. The expression levels of transient receptor potential vanilloid (TRPV) 1, TRPV3, TRPV4, and the pruritus-related mediators Substance P (SP), nerve growth factor (NGF), and calcitonin gene-related peptide (CGRP) in the skin lesions were analyzed using Western blot and qRT-PCR. The effect of evodiamine on the exploratory behavior, motor, and coordination abilities of mice was assessed using open field, suspension, and Rota-Rod experiments. Molecular docking was utilized to verify the binding of evodiamine to the residues of TRPV1, TRPV3, and TRPV4. Results: Evodiamine reduced pruritus and inhibited inflammation by decreasing the levels of inflammatory mediators TNF-α, IL-23, and IL-17A in the serum of Imiquimod-induced mice and attenuated the mRNA and protein expression levels of SP, NGF, CGRP, TRPV1, TRPV3, and TRPV4 in the skin. Conclusion: Evodiamine is an effective treatment for psoriasis and pruritus, due to its ability to inhibit immune inflammation and pruritic mediators.

2.
Animal Model Exp Med ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38952042

ABSTRACT

BACKGROUND: Artesunate (ASA) acts as an •O2- source through the breakdown of endoperoxide bridges catalyzed by Fe2+, yet its efficacy in ASA-based nanodrugs is limited by poor intracellular delivery. METHODS: ASA-hyaluronic acid (HA) conjugates were formed from hydrophobic ASA and hydrophilic HA by an esterification reaction first, and then self-targeting nanomicelles (NM) were developed using the fact that the amphiphilic conjugates of ASA and HA are capable of self-assembling in aqueous environments. RESULTS: These ASA-HA NMs utilize CD44 receptor-mediated transcytosis to greatly enhance uptake by breast cancer cells. Subsequently, endogenous Fe2+ from the tumor catalyzes the released ASA to produce highly toxic •O2- radicals to kill tumor cells, although sustained tumor growth inhibition can be achieved via in vivo experiments. CONCLUSIONS: Self-targeting NMs represent a promising strategy for enhancing ASA-based treatments, leveraging clinically approved drugs to expedite drug development and clinical research in oncology.

3.
Int J Mol Sci ; 25(11)2024 May 22.
Article in English | MEDLINE | ID: mdl-38891819

ABSTRACT

Photothermal therapy (PTT) is a promising cancer therapy modality with significant advantages such as precise targeting, convenient drug delivery, better efficacy, and minimal adverse effects. Photothermal therapy effectively absorbs the photothermal transducers in the near-infrared region (NIR), which induces the photothermal effect to work. Although PTT has a better role in tumor therapy, it also suffers from low photothermal conversion efficiency, biosafety, and incomplete tumor elimination. Therefore, the use of nanomaterials themselves as photosensitizers, the targeted modification of nanomaterials to improve targeting efficiency, or the combined use of nanomaterials with other therapies can improve the therapeutic effects and reduce side effects. Notably, noble metal nanomaterials have attracted much attention in PTT because they have strong surface plasmon resonance and an effective absorbance light at specific near-infrared wavelengths. Therefore, they can be used as excellent photosensitizers to mediate photothermal conversion and improve its efficiency. This paper provides a comprehensive review of the key role played by noble metal nanomaterials in tumor photothermal therapy. It also describes the major challenges encountered during the implementation of photothermal therapy.


Subject(s)
Metal Nanoparticles , Neoplasms , Photothermal Therapy , Humans , Photothermal Therapy/methods , Neoplasms/therapy , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Animals , Photosensitizing Agents/chemistry , Photosensitizing Agents/therapeutic use
4.
J Physiol Investig ; 67(3): 118-128, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38910572

ABSTRACT

MicroRNA-150-5p (miR-150-5p) has been implicated in the progression of several cancer types, yet its specific functional role and regulatory mechanisms in bladder cancer (BC) remain largely unexplored. Our study revealed significant downregulation of miR-150-5p and upregulation of NEDD4-binding protein 2-like 1 gene (N4BP2L1) in BC tissues compared to controls using quantitative real-time polymerase chain reaction and western blot analysis, respectively. Reduced miR-150-5p expression correlated with advanced tumor stage and lymph node metastasis, while increased N4BP2L1 levels were associated with larger tumor size by the Chi-square test. Functionally, miR-150-5p exerted significant inhibitory effects on BC cell proliferation, migration, inducing G0/G1 phase arrest, and apoptosis. We confirmed N4BP2L1 as a direct target of miR-150-5p in BC cells using luciferase reporter assay. Crucially, N4BP2L1 knockdown mimicked, while overexpression counteracted the inhibitory impacts of miR-150-5p on BC cell proliferation, migration, and invasion. In addition, N4BP2L1 overexpression reversed miR-150-5p-induced alterations in CDK4, Cyclin D1, Bcl-2, PCNA, Ki-67, N-cadherin, Bad, and E-cadherin levels in BC cells. Based on these results, it can be inferred that the miR-150-5p/N4BP2L1 axis might constitute a promising candidate for therapeutic targeting in the treatment of BC.


Subject(s)
Cell Movement , Cell Proliferation , MicroRNAs , Urinary Bladder Neoplasms , Aged , Female , Humans , Male , Middle Aged , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , MicroRNAs/metabolism , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/metabolism
5.
Microsyst Nanoeng ; 10: 89, 2024.
Article in English | MEDLINE | ID: mdl-38919161

ABSTRACT

With the increasing demand for multifunctional optoelectronic devices, flexible electrochromic energy storage devices are being widely recognized as promising platforms for diverse applications. However, simultaneously achieving high capacitance, fast color switching and large optical modulation range is very challenging. In this study, the MXene-based flexible in-plane microsupercapacitor was fabricated via a mask-assisted spray coating approach. By adding electrochromic ethyl viologen dibromide (EVB) into the electrolyte, the device showed a reversible color change during the charge/discharge process. Due to the high electronic conductivity of the MXene flakes and the fast response kinetics of EVB, the device exhibited a fast coloration/bleaching time of 2.6 s/2.5 s, a large optical contrast of 60%, and exceptional coloration efficiency. In addition, EVB acted as a redox additive to reinforce the energy storage performance; as a result, the working voltage window of the Ti3C2-based symmetric aqueous microsupercapacitor was extended to 1 V. Moreover, the device had a high areal capacitance of 12.5 mF cm-2 with superior flexibility and mechanical stability and showed almost 100% capacitance retention after 100 bending cycles. The as-prepared device has significant potential for a wide range of applications in flexible and wearable electronics, particularly in the fields of camouflage, anticounterfeiting, and displays.

6.
PLoS One ; 19(5): e0296414, 2024.
Article in English | MEDLINE | ID: mdl-38771805

ABSTRACT

Vasectomized mice play a key role in the production of transgenic mice. However, vasectomy can cause great physical and psychological suffering to mice. Therefore, there is an urgent need to find a suitable replacement for vasectomized mice in the production of transgenic mice. In this study, we generated C57BL/6J mice (Piwil1 D633A-INS99, Piwil1mt/mt) with a 99-base insertion in the Miwi (Piwil1) gene using CRISPR/Cas9 technology and showed that Piwil1mt/+ heterozygous mice were normally fertile and that homozygous Piwil1mt/mt males were sterile and females were fertile. Transplantation of normal fertilized eggs into wild pseudopregnant females following mating with Piwil1mt/mt males produced no Piwil1mt/mt genotype offspring, and the number of offspring did not differ significantly from that of pseudopregnant mice following mating and breeding with ligated males. The CRISPR‒Cas9 system is available for generating Miwi-modified mice, and provides a powerful resource to replace ligated males in assisted reproduction research.


Subject(s)
Argonaute Proteins , Pseudopregnancy , Animals , Female , Male , Mice , Argonaute Proteins/genetics , Argonaute Proteins/metabolism , CRISPR-Cas Systems , Mice, Inbred C57BL , Mice, Transgenic , Pseudopregnancy/genetics
7.
Int J Med Sci ; 21(6): 1003-1015, 2024.
Article in English | MEDLINE | ID: mdl-38774754

ABSTRACT

Objective: Asthma is a chronic heterogeneous airway disease, and imbalanced T-helper type 1 (Th1) and Th2 cell-mediated inflammation contribute to its pathogenesis. Although it has been suggested that androgen and estrogen were involved in development of asthma, the underlying mechanisms remained largely unclear. Studies have demonstrated that Runx3 could promote naive CD4+ T cells to differentiate into Th1 cells. Hence, our study aimed to explore the potential regulatory mechanism of androgen and estrogen on asthma via modulating Runx3. Methods: First, clinical assessments and pulmonary function tests were conducted on 35 asthma patients and 24 healthy controls. The concentrations of androgen, estrogen, and androgen estrogen ratios were assessed in peripheral blood samples of asthma patients and healthy controls. Then, a murine asthma model was established to explore the effects of estrogen and androgen (alone or in combination) on asthma. Third, an in vitro assay was used to explore the mechanism of combination of androgen and estrogen in asthma. Results: We observed decreased androgen and increased estrogen levels in asthma patients compared with healthy controls. In mice with experimental asthma, there were increased serum concentrations of estrogen and decreased serum concentrations of androgen, intervention with combination of androgen and estrogen alleviated airway inflammations, increased Runx3 expressions and elevated Th1 differentiation. In CD4+ T cells co-cultured with bronchial epithelial cells (BECs), treatment with androgen plus estrogen combination promoted Th1 differentiation, which was mitigated by Runx3 knockdown in BECs and enhanced by Runx3 overexpression. Conclusion: These findings suggest that androgen estrogen combination modulate the Th1/Th2 balance via regulating the expression of Runx3 in BECs, thereby providing experimental evidence supporting androgen and estrogen combination as a novel therapy for asthma.


Subject(s)
Androgens , Asthma , Core Binding Factor Alpha 3 Subunit , Estrogens , Adult , Animals , Female , Humans , Male , Mice , Middle Aged , Androgens/blood , Asthma/drug therapy , Asthma/immunology , Asthma/blood , Case-Control Studies , Cell Differentiation/drug effects , Core Binding Factor Alpha 3 Subunit/genetics , Core Binding Factor Alpha 3 Subunit/metabolism , Disease Models, Animal , Th1 Cells/immunology , Th1 Cells/drug effects , Th2 Cells/immunology , Th2 Cells/drug effects
9.
ACS Nano ; 18(21): 13528-13537, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38747549

ABSTRACT

Dental caries is a widespread oral disease that poses a significant medical challenge. Traditional caries prevention methods, primarily the application of fluoride, often fall short in effectively destroying biofilms and preventing enamel demineralization, thereby providing limited efficacy in halting the progression of caries over time. To address this issue, we have developed a green and cost-effective synergistic strategy for the prevention of dental caries. By combining natural sodium phytate and chitosan, we have created chitosan-sodium phytate nanoparticles that offer both the antimicrobial properties of chitosan and the enamel demineralization-inhibiting capabilities of sodium phytate. In an ex vivo biofilm model of human teeth, we found that these nanoparticles effectively prevent biofilm buildup and acid damage to the mineralized tissue. Additionally, topical treatment of dental caries in rodent models has shown that these nanoparticles effectively suppress disease progression without negatively impacting oral microbiota diversity or causing harm to the gingival-mucosal tissues, unlike traditional prevention methods.


Subject(s)
Biofilms , Chitosan , Dental Caries , Nanoparticles , Phytic Acid , Dental Caries/prevention & control , Chitosan/chemistry , Chitosan/pharmacology , Humans , Nanoparticles/chemistry , Phytic Acid/chemistry , Phytic Acid/pharmacology , Phytic Acid/administration & dosage , Animals , Biofilms/drug effects , Streptococcus mutans/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/administration & dosage , Mice
10.
Pharmaceutics ; 16(5)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38794265

ABSTRACT

Sonodynamic therapy (SDT) has attracted significant attention in recent years as it is an innovative approach to tumor treatment. It involves the utilization of sound waves or ultrasound (US) to activate acoustic sensitizers, enabling targeted drug release for precise tumor treatment. This review aims to provide a comprehensive overview of SDT, encompassing its underlying principles and therapeutic mechanisms, the applications of nanomaterials, and potential synergies with combination therapies. The review begins by introducing the fundamental principle of SDT and delving into the intricate mechanisms through which it facilitates tumor treatment. A detailed analysis is presented, outlining how SDT effectively destroys tumor cells by modulating drug release mechanisms. Subsequently, this review explores the diverse range of nanomaterials utilized in SDT applications and highlights their specific contributions to enhancing treatment outcomes. Furthermore, the potential to combine SDT with other therapeutic modalities such as photothermal therapy (PTT) and chemotherapy is discussed. These combined approaches aim to synergistically improve therapeutic efficacy while mitigating side effects. In conclusion, SDT emerges as a promising frontier in tumor treatment that offers personalized and effective treatment options with the potential to revolutionize patient care. As research progresses, SDT is poised to play a pivotal role in shaping the future landscape of oncology by providing patients with a broader spectrum of efficacious and tailored treatment options.

11.
Mol Biol Rep ; 51(1): 644, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727958

ABSTRACT

BACKGROUND: MicroRNAs are differentially expressed in periodontitis tissues. They are involved in cellular responses to inflammation and can be used as markers for diagnosing periodontitis. Microarray analysis showed that the expression level of microRNA-671-5p in periodontal tissues of patients with periodontitis was increased. In this study, we investigated the mechanism of action of microRNA-671-5p in human periodontal ligament stem cells (hPDLSCs) under inflammatory conditions. METHODS AND RESULTS: HPDLSCs were treated with lipopolysaccharide (LPS) to establish an inflammation model. The cell survival rate was determined using the cell counting kit-8 (CCK8). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analyses were used to detect the expression of microRNA-671-5p and dual-specificity phosphatase (DUSP) 8 proteins, respectively, Interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α were detected using qRT-PCR and Enzyme-linked immunosorbent assay (ELISA). A dual-luciferase reporter system was employed to determine the relationship between micoRNA-671-5p and DUSP8 expression. Activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway was confirmed using western blot analysis. Following the treatment of hPDLSCs with LPS, the expression levels of microRNA-671-5p in hPDLSCs were increased, cell viability decreased, and the expression of inflammatory factors displayed an increasing trend. MicroRNA-671-5p targets and binds to DUSP8. Silencing microRNA-671-5p or overexpressing DUSP8 can improve cell survival rate and reduce inflammatory responses. When DUSP8 was overexpressed, the expression of p-p38 was reduced. CONCLUSIONS: microRNA-671-5p targets DUSP8/p38 MAPK pathway to regulate LPS-induced proliferation and inflammation in hPDLSCs.


Subject(s)
Dual-Specificity Phosphatases , Inflammation , Lipopolysaccharides , MicroRNAs , Periodontal Ligament , Stem Cells , p38 Mitogen-Activated Protein Kinases , Humans , Cell Survival/genetics , Cell Survival/drug effects , Cells, Cultured , Dual-Specificity Phosphatases/genetics , Dual-Specificity Phosphatases/metabolism , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Lipopolysaccharides/pharmacology , MAP Kinase Signaling System/genetics , MAP Kinase Signaling System/drug effects , MicroRNAs/genetics , MicroRNAs/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Periodontal Ligament/metabolism , Periodontal Ligament/cytology , Periodontitis/genetics , Periodontitis/metabolism , Periodontitis/pathology , Signal Transduction/genetics , Stem Cells/metabolism
13.
Inorg Chem ; 63(20): 9297-9306, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38712902

ABSTRACT

The photocatalytic oxidation of benzyl alcohol and the simultaneous evolution of hydrogen from water are efficient dual-optimal routes. It is important to develop composite catalysts that combine redox properties and facilitate electron-hole separation and transport. Herein, the bimetallic-doped Mo-ZIS@Ti photocatalyst was designed and synthesized, and the selective oxidation of benzyl alcohol and hydrogen evolution by water splitting was realized at the same time. Under visible light irradiation, benzyl alcohol was completely converted with more than 99% selectivity for benzaldehyde, and the H2 production rate was 5.6 times higher than the initial ZIS. The exceptional catalytic performance was ascribed to utilizing Ti-MIL-125 as a precursor, wherein slowly releasing-doped Ti formed robust Ti-S bonds that quickly transfer electrons and reduce sites. Meanwhile, doping Mo effectively captures photogenerated holes and acts as active sites for oxidation reactions. Both experimental characterization and work function calculations demonstrate that the bimetallic synergism effectively modulates the electronic structure of ZIS, promotes the directional separation of electrons and holes, and significantly improves the photoactivity and stability of ZIS. This work contributes a route to obtain benzaldehyde and green hydrogen at the same time and also gives new insights for the construction and mechanism study of bimetallic-doping catalysts.

14.
Nat Commun ; 15(1): 4330, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773072

ABSTRACT

The Hendra and Nipah viruses (HNVs) are highly pathogenic pathogens without approved interventions for human use. In addition, the interaction pattern between the attachment (G) and fusion (F) glycoproteins required for virus entry remains unclear. Here, we isolate a panel of Macaca-derived G-specific antibodies that cross-neutralize HNVs via multiple mechanisms. The most potent antibody, 1E5, confers adequate protection against the Nipah virus challenge in female hamsters. Crystallography demonstrates that 1E5 has a highly similar binding pattern to the receptor. In cryo-electron microscopy studies, the tendency of 1E5 to bind to the upper or lower heads results in two distinct quaternary structures of G. Furthermore, we identify the extended outer loop ß1S2-ß1S3 of G and two pockets on the apical region of fusion (F) glycoprotein as the essential sites for G-F interactions. This work highlights promising drug candidates against HNVs and contributes deeper insights into the viruses.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Cryoelectron Microscopy , Henipavirus Infections , Viral Fusion Proteins , Animals , Antibodies, Neutralizing/immunology , Female , Antibodies, Viral/immunology , Henipavirus Infections/virology , Henipavirus Infections/immunology , Viral Fusion Proteins/immunology , Viral Fusion Proteins/chemistry , Humans , Viral Envelope Proteins/immunology , Viral Envelope Proteins/chemistry , Nipah Virus/immunology , Virus Internalization/drug effects , Henipavirus/immunology , Cricetinae , Cross Reactions/immunology , Hendra Virus/immunology , Macaca , Mesocricetus , Crystallography, X-Ray
15.
Eur Spine J ; 33(6): 2179-2189, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38647605

ABSTRACT

OBJECTIVE: Tubular microdiskectomy (tMD) is one of the most commonly used for treating lumbar disk herniation. However, there still patients still complain of persistent postoperative residual low back pain (rLBP) postoperatively. This study attempts to develop a nomogram to predict the risk of rLBP after tMD. METHODS: The patients were divided into non-rLBP (LBP VAS score < 2) and rLBP (LBP VAS score ≥ 2) group. The correlation between rLBP and these factors were analyzed by multivariate logistic analysis. Then, a nomogram prediction model of rLBP was developed based on the risk factors screened by multivariate analysis. The samples in the model are randomly divided into training and validation sets in a 7:3 ratio. The Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the diskrimination, calibration and clinical value of the model, respectively. RESULTS: A total of 14.3% (47/329) of patients have persistent rLBP. The multivariate analysis suggests that higher preoperative LBP visual analog scale (VAS) score, lower facet orientation (FO), grade 2-3 facet joint degeneration (FJD) and moderate-severe multifidus fat atrophy (MFA) are risk factors for postoperative rLBP. In the training and validation sets, the ROC curves, calibration curves, and DCAs suggested the good diskrimination, predictive accuracy between the predicted probability and actual probability, and clinical value of the model, respectively. CONCLUSION: This nomogram including preoperative LBP VAS score, FO, FJD and MFA can serve a promising prediction model, which will provide a reference for clinicians to predict the rLBP after tMD.


Subject(s)
Intervertebral Disc Displacement , Low Back Pain , Lumbar Vertebrae , Nomograms , Humans , Low Back Pain/etiology , Low Back Pain/surgery , Male , Female , Middle Aged , Lumbar Vertebrae/surgery , Adult , Intervertebral Disc Displacement/surgery , Diskectomy/adverse effects , Diskectomy/methods , Postoperative Complications/etiology , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Risk Factors , Aged
16.
Adv Mater ; 36(28): e2402480, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38657757

ABSTRACT

The perovskite/Cu(InGa)Se2 (CIGS) tandem solar cells (TSCs) presents a compelling technological combination poised for the next generation of flexible and lightweight photovoltaic (PV) tandem devices, featuring a tunable bandgap, high power conversion efficiency (PCE), lightweight flexibility, and enhanced stability and durability. Over the years, the imperative to enhance the performance of wide bandgap (WBG) perovskite solar cells (PSCs) has grown significantly, particularly in the context of a flexible tandem device. In this study, an all-round passivation strategy known as Dual Passivation at Grains and Interfaces (DPGI) is introduced for WBG PSCs in perovskite/CIGS tandem structures. The implementation of DPGI is tailored to improve film crystallinity and passivate defects across the solar cell structure, leading to a substantial performance enhancement for WBG PSCs. Subsequently, both rigid and flexible tandem devices are assembled. Impressively, a fully flexible 4T perovskite/CIGS TSCs is successfully fabricated with a PCE of 26.57%, making it the highest value in this field and highlighting its potential applications in the next generation of flexible lightweight PV tandem devices.

17.
Toxicol Res (Camb) ; 13(2): tfae064, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38680951

ABSTRACT

Background: Postmenopausal osteoporosis (PMPO) is the most familiar type of osteoporosis, a silent bone disease. Casticin, a natural flavonoid constituent, improves osteoporosis in animal model. Nevertheless, the potential mechanism remains to be further explored. Methods: A model of PMPO was established in rats treated with ovariectomy (OVX) and RAW 264.7 cells induced with receptor activator of nuclear factor kappa-B ligand (RANKL). The effect and potential mechanism of casticin on PMPO were addressed by pathological staining, measurement of bone mineral density (BMD), three-point bending test, serum biochemical detection, filamentous-actin (F-actin) ring staining, TRAcP staining, reverse transcription quantitative polymerase chain reaction, western blot and examination of oxidative stress indicators. Results: The casticin treatment increased the femoral trabecular area, bone maturity, BMD, elastic modulus, maximum load, the level of calcium and estrogen with the reduced concentrations of alkaline phosphatase (ALP) and tumor necrosis factor (TNF)-α in OVX rats. An enhancement in the F-actin ring formation, TRAcP staining and the relative mRNA expression of NFATc1 and TRAP was observed in RANKL-induced RAW 264.7 cells, which was declined by the treatment of casticin. Moreover, the casticin treatment reversed the reduced the relative protein expression of Nrf2 and HO-1 and the concentrations of superoxide dismutase and glutathione peroxidase, and the increased content of malondialdehyde both in vivo and in vitro. Conclusion: Casticin improved bone density, bone biomechanics, the level of calcium and estrogen, the release of pro-inflammatory factor and oxidative stress to alleviate osteoporosis, which was associated with the upregulation of Nrf2/HO-1 pathway.

18.
Heliyon ; 10(7): e28884, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38601672

ABSTRACT

Objective: Asthma, a chronic inflammatory disease in which type 2 T helper cells (Th2) play a causative role in the development of T2 asthma. N6-methyladenosine (m6A) modification, an mRNA modification, and methyltransferase-like 3 (METTL3) is involved in the development of T2 asthma by inhibiting Th2 cell differentiation. Sex determining region Y-box protein 5 (SOX5) is involved in regulating T cell differentiation, but its role in T2 asthma was unclear. The objective of this study was to explore the role of METTL3 and SOX5 in T2 asthma and whether there is an interaction between the two. Materials and methods: Adults diagnosed with T2 asthma (n = 14) underwent clinical information collection and pulmonary function tests. In vivo and in vitro T2 asthma models were established using female C57BL/6 mice and human bronchial epithelial cells (HBE). The expressions of METTL3 and SOX5 were detected by Western blot and qRT-PCR and Western blot. Th2 cell differentiation was determined by flow cytometry and IL-4 level was detected by ELISA. m6A methylation level was determined by m6A quantitative assay. The relationship between METTL3 expression and clinical parameters was determined by Spearman rank correlation analysis. The function of METTL3 and SOX5 genes in asthma was investigated in vitro and in vivo. The RNA immunoprecipitation assay detected the specific interaction between METTL3 and SOX5. Results: Patients with T2 asthma displayed lower METTL3 levels compared to healthy controls. Within this group, a negative correlation was observed between METTL3 and Th2 cells, while a positive correlation was noted between METTL3 and clinical parameters as well as Th1 cells. In both in vitro and in vivo models representing T2 asthma, METTL3 levels decreased significantly, while SOX5 levels showed the opposite trend. Overexpression of METTL3 gene in HBE cells significantly inhibited Th2 cell differentiation and increased m6A methylation activity. From a mechanism perspective, low METTL3 negatively regulates SOX5 expression through m6A modification dependence, while high SOX5 expression is positively associated with T2 asthma severity. Cell transfection experiments confirmed that METTL3 regulates Th2 cell differentiation and IL-4 release through SOX5. Conclusions: Overall, our results indicate that METTL3 alleviates Th2 cell differentiation in T2 asthma by modulating the m6A methylation activity of SOX5 in bronchial epithelial cells. This mechanism could potentially serve as a target for the prevention and management of T2 asthma.

19.
ACS Nano ; 18(18): 11910-11920, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38680054

ABSTRACT

Personalized antitumor immunotherapy utilizing neoantigen vaccines holds great promise. However, the limited immunogenicity of existing recognized neoantigens and the inadequate stimulation of antitumor immune responses by conventional adjuvants pose significant challenges. To address these limitations, we developed a nanovaccine that combines a BCG bacterial cell wall skeleton (BCG-CWS) based nanoscale adjuvant (BCNA) with peptide neoantigens (M27 and M30). This integrated approach provides an efficient translational strategy for cancer immunotherapy. The BCNA nanovaccine, formulated with PLGA as an emulsifier, exhibits excellent biocompatibility and superior antigen presentation compared with conventional BCG-CWS adjuvants. Subcutaneous immunization with the BCNA-based nanovaccine effectively targets lymph nodes, eliciting robust innate and tumor-specific immune responses. Importantly, our findings demonstrate that BCNAs significantly enhance neoantigen immunogenicity while minimizing acute systemic toxicity. Furthermore, when combined with a mouse PD-L1 antibody, our strategy achieves complete tumor elimination in 60% of cases and prevents 25% of tumor growth in a melanoma mouse model. In conclusion, our BCNA-based nanovaccine represents a promising avenue for advancing personalized therapeutic neoantigen vaccines and holds significant implications for enhancing personalized immunotherapy and improving patient outcomes in the field of cancer treatment.


Subject(s)
Adjuvants, Immunologic , Cancer Vaccines , Immunotherapy , Animals , Cancer Vaccines/immunology , Cancer Vaccines/administration & dosage , Mice , Mice, Inbred C57BL , Antigens, Neoplasm/immunology , Female , Humans , Cell Wall/immunology , Cell Wall/chemistry , Mycobacterium bovis/immunology , Nanoparticles/chemistry , BCG Vaccine/immunology , Cell Line, Tumor
20.
Environ Sci Technol ; 58(17): 7357-7366, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38568220

ABSTRACT

Although sulfur cycling in acid mine drainage (AMD)-contaminated rice paddy soils is critical to understanding and mitigating the environmental consequences of AMD, potential sources and transformations of organosulfur compounds in such soils are poorly understood. We used sulfur K-edge X-ray absorption near edge structure (XANES) spectroscopy to quantify organosulfur compounds in paddy soils from five AMD-contaminated sites and one AMD-uncontaminated reference site near the Dabaoshan sulfide mining area in South China. We also determined the sulfur stable isotope compositions of water-soluble sulfate (δ34SWS), adsorbed sulfate (δ34SAS), fulvic acid sulfur (δ34SFAS), and humic acid sulfur (δ34SHAS) in these samples. Organosulfate was the dominant functional group in humic acid sulfur (HAS) in both AMD-contaminated (46%) and AMD-uncontaminated paddy soils (42%). Thiol/organic monosulfide contributed a significantly lower proportion of HAS in AMD-contaminated paddy soils (8%) compared to that in AMD-uncontaminated paddy soils (21%). Within contaminated soils, the concentration of thiol/organic monosulfide was positively correlated with cation exchange capacity (CEC), moisture content (MC), and total Fe (TFe). δ34SFAS ranged from -6.3 to 2.7‰, similar to δ34SWS (-6.9 to 8.9‰), indicating that fulvic acid sulfur (FAS) was mainly derived from biogenic S-bearing organic compounds produced by assimilatory sulfate reduction. δ34SHAS (-11.0 to -1.6‰) were more negative compared to δ34SWS, indicating that dissimilatory sulfate reduction and abiotic sulfurization of organic matter were the main processes in the formation of HAS.


Subject(s)
Mining , Oryza , Soil Pollutants , Soil , Soil/chemistry , Oryza/chemistry , Humic Substances , Sulfur , Sulfur Compounds
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