ABSTRACT
Kunzea ericoides (kanuka) products are well-known for their potent medicinal values in antioxidant and anti-inflammatory applications. The present study identified various compounds, such as chlorogenic acid, gallic acid, quercetin, and (E)-ferulic acid in the kanuka leaf extract, showing its potential use in maintaining skin health. The influence of kanuka leaf extract upon epidermal cells concerning cytotoxicity and in vitro activities of moisturisation, antioxidation, UV protection, and anti-melanogenesis effects were explored in the study. Kanuka leaf extract demonstrated significant promotion in the proliferation of HaCaT and B16F10 cells. After incubation with kanuka leaf extract, the content of ROS and DPPH in HaCaT was significantly decreased; at the same time, more SOD was produced. Furthermore, hyaluronidase-1 (HYAL-1) and HYAL-4 expressions were inhibited, while the aquaporin 3 (AQP-3) content was significantly increased in HaCaT. Kanuka leaf extract also inhibited the expressions of matrix metalloproteinases-1 (MMP-1) and MMP-14 in UV-induced HaCaT cells. In the B16F10 cell line, melanin and tyrosinase production were decreased under the presence of kanuka leaf extract, and the expressions of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TYRP-1), and TYRP-2 were also inhibited. The study validated kanuka leaf extract as an effective natural product against photoaging and melanogenesis.
ABSTRACT
This paper presents a micromachined thermal convective accelerometer with low power and high reliability. This accelerometer comprises a heater and two thermistors. The central heater elevates the temperature of the chip above ambient levels while the symmetrically arranged thermistors monitor the temperature differentials induced by acceleration. The heater and thermistors are fabricated on a glass substrate using a standard micro-electromechanical systems (MEMS) process flow, and the fabricated sensor is installed on a rotation platform and a shaking table experimental setup to perform the experiment. The results indicate that the sensor has the capability to measure accelerations surpassing 80 m/s2, with an approximate linear sensitivity of 110.69 mV/g. This proposed thermal convective accelerometer offers promising potential for various applications requiring precise acceleration measurements in environments where low power consumption and high reliability are paramount.
ABSTRACT
The protracted transition from inflammation to proliferation in diabetic wound healing poses significant challenges, exacerbated by persistent inflammatory responses and inadequate vascularization. To address these issues, a novel nanozymatic therapeutic approach utilizing asymmetrically structured MnO2-Au-mSiO2@aFGF Janus nanoparticles is engineered. Nanozymes featuring a mSiO2 head and MnO2 extensions, into which acidic fibroblast growth factor (aFGF) is encapsulated, resulting in MnO2-Au-mSiO2@aFGF Janus nanoparticles (mSAM@aFGF), are synthesized. This nanozyme system effectively emulates enzymatic activities of catalase (CAT) and superoxide dismutase (SOD), catalyzing degradation of reactive oxygen species (ROS) and generating oxygen. In addition, controlled release of aFGF fosters tissue regeneration and vascularization. In vitro studies demonstrate that mSAM@aFGF significantly alleviates oxidative stress in cells, and enhances cell proliferation, migration, and angiogenesis. An injectable hydrogel based on photocrosslinked hyaluronic acid (HAMA), incorporating the nanozymatic ROS-scavenging and growth factor-releasing system, is developed. The HAMA-mSAM@aFGF hydrogel exhibits multifaceted benefits in a diabetic wound model, including injectability, wound adhesion, hemostasis, anti-inflammatory effects, macrophage polarization from M1 to M2 phenotype, and promotion of vascularization. These attributes underscore the potential of this system to facilitate transition from chronic inflammation to the proliferative phase of wound repair, offering a promising therapeutic strategy for diabetic wound management.
ABSTRACT
Lethal(3)malignant brain tumor-like protein 2 (L3MBTL2) has been related to transcriptional inhibition and chromatin compaction. Nevertheless, the biological functions and mechanisms of L3MBTL2 are undefined in breast cancer (BRCA). Here, we revealed that L3MBTL2 is responsible for the decline of Nischarin (NISCH), a well-known tumor suppressor, in BRCA, and explored the detailed mechanism. Knockdown of L3MBTL2 reduced monoubiquitination of histone H2A at lysine-119 (H2AK119ub), leading to reduced binding to the NISCH promoter and increased expression of NISCH. Meanwhile, the knockdown of L3MBTL2 decreased proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of BRCA cells, and increased apoptosis, which were abated by NISCH knockdown. Nucleolar transcription factor 1 (UBTF) induced the transcription of L3MBTL2 in BRCA, and the suppressing effects of UBTF silencing on EMT in BRCA cells were also reversed by NISCH knockdown. Knockdown of UBTF slowed tumor progression and attenuated lung tumor infiltration, whereas simultaneous knockdown of NISCH accelerated EMT and increased tumor lung metastasis. Taken together, our results show that L3MBTL2, transcriptionally activated by UBTF, exerts oncogenic functions in BRCA, by catalyzing H2AK119Ub and reducing expression of NISCH.
ABSTRACT
Disseminated adenovirus infection is a complication with a relatively high mortality rate among patients undergoing hematopoietic stem cell transplantation. The low efficacy and poor availability of current treatment options are of major concern. Programmed cell death 1 (PD-1) blockade has been used to treat several chronic viral infections. Herein, we report a case of disseminated adenovirus infection in the early posttransplant period. The patient was diagnosed with diffuse large B-cell lymphoma at first and underwent 8 cycles of chemotherapy, including rituximab. She was subsequently diagnosed with acute myeloid leukemia and received haploidentical transplantation. She was diagnosed with EpsteinâBarr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) 2 months after the transplant, and 3 doses of rituximab were administered. The patient was diagnosed with disseminated adenovirus infection with upper respiratory tract, gastrointestinal tract and blood involved at 3 months after transplantation. She was first treated with a reduction in immunosuppression, cidofovir and ribavirin. Then, the patient received salvage treatment with the PD-1 inhibitor sintilimab (200 mg) after achieving no response to conventional therapy. The adenovirus was cleared 3 weeks later, and concomitant EBV was also cleared. Although the patient developed graft-versus-host disease of the liver after the administration of the PD-1 inhibitor, she was cured with steroid-free therapy. Therefore, PD-1 blockade immunotherapy can be considered a promising treatment option for patients with disseminated adenovirus infection after transplantation, with fully weighing the hazards of infection and the side effects of this therapy.
Subject(s)
Hematopoietic Stem Cell Transplantation , Programmed Cell Death 1 Receptor , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Female , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Immune Checkpoint Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Immunotherapy/methods , Middle Aged , Transplantation, Homologous , Adenoviridae Infections/drug therapy , Adenovirus Infections, Human/drug therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/drug therapyABSTRACT
Platinum group metals (PGMs) are strategic metals. Auto-exhaust catalysts are their main application fields. The recovery of PGMs from spent auto-exhaust catalysts has remarkable economic value and strategic significance. Aiming at the problems of ferrosilicon generation for Fe capturing and subsequent oxygen blowing to remove iron with high energy consumption and heat release, a technology of Fe-Sn synergistic capturing PGMs was proposed. Taking full the advantage of the lower melting point of Fe-Sn alloy (<1200 °C) and its unique affinity for PGMs, the PGMs were captured at approximate 1400 °C with Fe-Sn as the collector. In experiment, 500 g of spent auto-exhaust catalysts were employed to minimize error and approximate industrial production. The mechanism of Fe-Sn synergistic capturing PGMs was elucidated. The generation of Fe-Sn-PGMs alloy lowered the activity of [PGMs] in the system, accelerated the reduction of the PGMs oxides and promoted the alloying of [PGMs]. Therefore, Fe-Sn synergistic capturing PGMs was realized. The inability of Si to enter the alloy phase was confirmed by theoretical calculations, avoiding the generation of ferrosilicon. The effects of basicity, CaF2, m(Fe)/m(Sn) and the amount of collector on capturing PGMs were optimized. Under the optimized conditions (basicity R = 1.1, spent auto-exhaust catalysts 70 wt%, CaO 30 wt%, B2O3 10 wt%, CaF2 7 wt%, m(Fe)/m(Sn) = 1/1 and the collector 15 wt%), the content of PGMs in the slag phase was 2.46 g/t. It is feasible to remove Fe and Sn by oxidation to achieve the purpose of PGMs enrichment. This technology offers guidance on the safe, environmentally sound, and efficient disposal of spent auto-exhaust catalysts, promoting the sustainable development of PGMs.
Subject(s)
Iron , Platinum , Platinum/chemistry , Iron/chemistry , Catalysis , Metals/chemistry , Tin/chemistry , Alloys/chemistryABSTRACT
Baicalein has been implicated in the chemotherapy overcoming triple-negative breast cancer (TNBC). However, many unanswered questions remain regarding its role in treating TNBC. Here, we sought to demonstrate the molecular pathway mediated by baicalein in TNBC. Lysine-specific demethylase 4E (KDM4E), reduced in TNBC cells, was identified as a target protein of baicalein, and baicalein enhanced the protein expression and stability of KDM4E in TNBC cells. Knockdown of KDM4E attenuated the inhibitory effect of baicalein on TNBC cell activity, as demonstrated by intensified mobility, viability, and apoptosis resistance in TNBC cells. KDM4E activated protein bicaudal D homolog 1 (BICD1) expression by reducing the deposition of histone H3 lysine 9 trimethylation (H3K9me3) in its promoter, whereas BICD1 promoted protease-activated receptor-1 (PAR1) endocytosis and blocked PAR1 signaling through physical interaction with PAR1. Knockdown of KDM4E strengthened the PAR1-dependent activity of TNBC cells in response to thrombin activation, whereas TNBC progression activated by PAR1 signaling was blocked by combined overexpression of BICD1. Taken together, our data indicate that baicalein-promoted KDM4E enhanced the expression of BICD1 and activated the inhibitory effect of BICD1 on PAR1 signaling, thereby inhibiting TNBC progression.
Subject(s)
Flavanones , Signal Transduction , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/genetics , Flavanones/pharmacology , Female , Signal Transduction/drug effects , Cell Line, Tumor , Animals , Receptor, PAR-1/metabolism , Receptor, PAR-1/genetics , Gene Expression Regulation, Neoplastic/drug effects , Cell Proliferation/drug effects , Apoptosis/drug effects , Disease Progression , MiceSubject(s)
Lymphohistiocytosis, Hemophagocytic , Nitriles , Pyrazoles , Pyrimidines , Humans , Lymphohistiocytosis, Hemophagocytic/drug therapy , Nitriles/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Male , Female , Adult , Antibodies, Monoclonal/therapeutic use , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adolescent , Aged , Young AdultABSTRACT
The one-pot MAC (Masked Acyl Cyanide) reaction is used to perform the tandem oxyhomologation reaction of N,N-dibenzyl-l-phenylalaninal and coupling with nitrogen nucleophiles to provide a wide selection of amide and peptide derivatives of (2S,3S)-allophenylnorstatin in generally good yields and with high anti selectivity, often with dr >98:2. The procedure works equally well with other selected N,N-dibenzyl α-amino aldehydes, and is used to achieve a very short synthesis of (2S,3S,S)-epibestatin.
Subject(s)
Amides , Peptides , Amides/chemistry , Stereoisomerism , Amino Acids/chemistry , CyanidesABSTRACT
Background: Hypertrophic scar (HS) is a common fibroproliferative skin disease that currently has no truly effective therapy. Given the importance of phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) in hypertrophic scar formation, the development of therapeutic strategies for endogenous inhibitors against PIK3CA is of great interest. Here, we explored the molecular mechanisms underlying the protective effects of miR-203a-3p (PIK3CA inhibitor) against excessive scar. Methods: Bioinformatic analysis, immunohistochemistry, immunofluorescence, miRNA screening and fluorescence in situ hybridization assays were used to identify the possible pathways and target molecules mediating HS formation. A series of in vitro and in vivo experiments were used to clarify the role of PIK3CA and miR-203a-3p in HS. Mechanistically, transcriptomic sequencing, immunoblotting, dual-luciferase assay and rescue experiments were executed. Results: Herein, we found that PIK3CA and the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway were upregulated in scar tissues and positively correlated with fibrosis. We then identified miR-203a-3p as the most suitable endogenous inhibitor of PIK3CA. miR-203a-3p suppressed the proliferation, migration, collagen synthesis and contractility as well as the transdifferentiation of fibroblasts into myofibroblasts in vitro, and improved the morphology and histology of scars in vivo. Mechanistically, miR-203a-3p attenuated fibrosis by inactivating the PI3K/AKT/mTOR pathway by directly targeting PIK3CA. Conclusions: PIK3CA and the PI3K/AKT/mTOR pathway are actively involved in scar fibrosis and miR-203a-3p might serve as a potential strategy for hypertrophic scar therapy through targeting PIK3CA and inactivating the PI3K/AKT/mTOR pathway.