Rationale: Growing evidence indicates that intracellular reactive oxygen species (ROS) accumulation is a critical factor in the development of osteoporosis by triggering osteoclast formation and function.Pseurotin A (Pse) is a secondary metabolite isolated from Aspergillus fumigatus with antioxidant properties, recently shown to exhibit with a wide range of potential therapeutic applications.However, its effects on osteoporosis remain unknown.This study aimed to explore whether Pse, by suppressing ROS levels, is able to inhibit osteoclastogenesis and prevent the bone loss induced by estrogen-deficiency in ovariectomized (OVX) mice. Methods:The effects of Pse on receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis and bone resorptive function were examined by tartrate resistant acid phosphatase (TRAcP) staining and hydroxyapatite resorption assay.2',7'dichlorodihydrofluorescein diacetate (H2DCFDA) was used to detect intracellular ROS production in vitro.Western blot assay was used to identify proteins associated with ROS generation and scavenging as well as ROS-mediated signaling cascades including mitogenactivated protein kinases (MAPKs), NF-κB pathways, and nuclear factor of activated T cells 1 (NFATc1) activation.The expression of osteoclast-specific genes was assessed by qPCR.The in vivo potential of Pse was determined using an OVX mouse model administered with Pse or vehicle for 6 weeks.In vivo ROS production was assessed by intravenous injection of dihydroethidium (DHE) into OVX mice 24h prior to killing.After sacrifice, the bone samples were analyzed using μCT and histomorphometry to determine bone volume, osteoclast activity, and ROS level in vivo.Results: Pse was demonstrated to inhibit osteoclastogenesis and bone resorptive function in vitro, as well as the downregulation of osteoclast-specific genes including Acp5 (encoding TRAcP), Ctsk (encoding cathepsin K), and Mmp9 (encoding matrix metalloproteinase 9).Mechanistically, Pse suppressed intracellular ROS level by inhibiting RANKL-induced ROS production and enhancing ROS scavenging enzymes, subsequently suppressing MAPK pathway activation (ERK, P38, and JNK) and NF-κB pathways, as well as inhibiting NFATc1 signaling.μCT and histological results indicated that OVX resulted in significant bone loss, with dramatically increased numbers of osteoclasts on the bone surface as well as increased ROS levels in the bone marrow microenvironment; whereas Pse supplementation was capable of effectively preventing these OVX-induced changes. Conclusion:Pse was demonstrated for the first time as a novel alternative therapy for osteoclastrelated bone disease such as osteoporosis through suppressing ROS levels.
The phytochemical constituent investigation on the 70 % ethanol extract of the rhizomes of Tupistra chinensis Baker resulted in the isolation of three new steroidal saponins which were named tuchinosides A-C (1-3). Their structures were determined by extensive spectrum analysis and chemical evidence, especially 2D NMR and HR-ESI-MS techniques. In addition, the cytotoxicity of compounds 1-3 against several human cancer cell lines was evaluated.
The iron response element (IRE) is a highly conserved RNA stem loop structure. It is the binding site of iron regulatory protein (IRP). IRP binding to IRE is regulated by cellular iron. When cells are derived of iron, IRP binds IRE. If IRE is located at 5'UTR, IRP binding will inhibit translation initiation, else if IRE is at 3'UTR, IRP binding will stabilize mRNA and prevent it from degradation. So far all known IREs have C at the 1 position and G at the 5 position of the loop (C1G5 type). In vitro studies suggest that the U1A5 type IRE, which has U and A at the 1 and 5 loop position respectively, binds well to IRP. However, U1A5 type's in vivo existence is still elusive. IRE-IRP binding is involved in the regulation of iron metabolism, oxidative stress and possibly aging. Here we use an improved computation method performing a comprehensive search of IRE in human and mouse genes. We try to catalog potential human and mouse IRE containing genes, at the same time identify potential U1A5 IREs.
In this paper the author discusses emphatically the spectral properties (absorption spectrum, fluorescence spectrum, excited lifetime and relative quantum yield) of three new dyes and compares their differences which come from the molecular structure. In the mean time the author introduce the experimental technology used to measure the spectra to determine the excited time in the picosecond range.
Nucleus pulposus-like differentiation is always the challenge with application of stem cells for intervertebral disc repair. The combination of injectable biomaterials and stem cells may provide a resolution for this problem, as the transmembrane force can affect the intracellular environment through integrin αβ. In this study, we developed a strategy of photo-crosslinked gelatin-hyaluronic acid methacrylate (GelHA) hydrogel to commit the nucleus pulposus-like differentiation of adipose stromal cells (ASCs) for intervertebral disc repair. ASCs were isolated and cultured in GelHA hydrogel to evaluate nucleus pulposus-like differentiation. The function of integrin αvβ6 was investigated with neutralising antibody. The efficacy of ASCs with GelHA hydrogel for intervertebral disc repair was studied in a rat model of intervertebral disc degeneration. The results showed that GelHA hydrogel promoted ASCs nucleus pulposus-like differentiation and that integrin αvβ6 neutralising antibody prevented ASCs from expression of nucleus pulposus matrix in vitro. The combination of GelHA hydrogel and ASCs promoted quality intervertebral disc repair in rats with much more nucleus pulposus matrix and significantly higher disc height index. The findings have demonstrated that the combination of photo-crosslinked GelHA hydrogel and ASCs can commit ASCs to nucleus pulposus-like differentiation and improve the efficacy of ASCs for intervertebral disc repair. These findings suggest a promising stem cell-based strategy for intervertebral disc repair.
To study the levels of genetic diversity, and population structure, of Houttuynia cordata Thunb, the genetic background and relationships of populations were analyzed in terms of environmental factors. The genetic diversity and population structure of H. cordata were investigated using sequence-related amplified polymorphisms and correlation with environmental factors was analyzed using the SPSS software. Two thousand one hundred sixty-three sites were amplified from 41 pairs of primers, 1825 of which were polymorphic, and the percentage of polymorphic loci was 84.37%; the percentage of polymorphic sites was 72.14 and 67.77% at the species and population level, respectively. The observed number of alleles was 1.52 and 1.30 at species and population level, respectively. The effective number of alleles was 1.38 and 1.24 at species and population level, respectively. The Nei's diversity was 0.26 and 0.15 at species and population level, respectively. The Shannon's information index was 0.87 and 0.63 at species and population level, respectively. The genetic differentiation coefficient of populations was 0.51, and 12 populations were divided into three classes based on D = 0.20; the genetic diversities of different populations are correlated at different significance levels (P < 0.05) with environmental factors. Genetic differentiation existed among populations and the populations exhibited heteroplasmy.
Background Coronavirus disease (COVID-19), caused by SARS-CoV-2, has emerged as a infectious disease, coexisting with widespread seasonal and sporadic influenza epidemics globally. Individuals living with HIV, characterized by compromised immune systems, face an elevated risk of severe outcomes and increased mortality when affected by COVID-19. Despite this connection, the molecular intricacies linking COVID-19, influenza, and HIV remain unclear. Our research endeavors to elucidate the shared pathways and molecular markers in individuals with HIV concurrently infected with COVID-19 and influenza. Furthermore, we aim to identify potential medications that may prove beneficial in managing these three interconnected illnesses. Methods Sequencing data for COVID-19 (GSE157103), influenza (GSE185576), and HIV (GSE195434) were retrieved from the GEO database. Commonly expressed differentially expressed genes (DEGs) were identified across the three datasets, followed by immune infiltration analysis and diagnostic ROC analysis on the DEGs. Functional enrichment analysis was performed using GO/KEGG and Gene Set Enrichment Analysis (GSEA). Hub genes were screened through a Protein-Protein Interaction networks (PPIs) analysis among DEGs. Analysis of miRNAs, transcription factors, drug chemicals, diseases, and RNA-binding proteins was conducted based on the identified hub genes. Finally, quantitative PCR (qPCR) expression verification was undertaken for selected hub genes. Results The analysis of the three datasets revealed a total of 22 shared DEGs, with the majority exhibiting an area under the curve value exceeding 0.7. Functional enrichment analysis with GO/KEGG and GSEA primarily highlighted signaling pathways associated with ribosomes and tumors. The ten identified hub genes included IFI44L , IFI44 , RSAD2 , ISG15 , IFIT3 , OAS1 , EIF2AK2 , IFI27 , OASL , and EPSTI1 . Additionally, five crucial miRNAs (hsa-miR-8060, hsa-miR-6890-5p, hsa-miR-5003-3p, hsa-miR-6893-3p, and hsa-miR-6069), five essential transcription factors (CREB1, CEBPB, EGR1, EP300, and IRF1), and the top ten significant drug chemicals (estradiol, progesterone, tretinoin, calcitriol, fluorouracil, methotrexate, lipopolysaccharide, valproic acid, silicon dioxide, cyclosporine) were identified. Conclusion This research provides valuable insights into shared molecular targets, signaling pathways, drug chemicals, and potential biomarkers for individuals facing the complex intersection of COVID-19, influenza, and HIV. These findings hold promise for enhancing the precision of diagnosis and treatment for individuals with HIV co-infected with COVID-19 and influenza.
One of the leading causes of death in the world is cerebrovascular disease. Numerous Chinese traditional medicines, such as Cortex Moutan (root bark of Paeonia suffruticosa Andrew) and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge), protect against cerebrovascular diseases and exhibit anti-atherosclerotic effects. Traditional medicines have been routinely used for a long time in China. In addition, these two herbs are prescribed together in clinical practice. Therefore, the pharmacodynamic interactions between the active constituents of these two herbs, which are paeonol (Pae) and danshensu (DSS), should be particularly studied. The study of Pae and DSS can provide substantial foundations in understanding their mechanisms and empirical evidence to support clinical practice. This study investigated the effects and possible mechanisms of the pharmacodynamic interaction between Pae and DSS on cerebrovascular malfunctioning in diabetes. Experimental diabetes was induced in rats, which was then treated with Pae, DSS, and Pae + DSS for eight weeks. Afterward, cerebral arteries from all groups were isolated and equilibrated in an organ bath with Krebs buffer and ring tension. Effects of Pae, DSS, and Pae + DSS were observed on vessel relaxation with or without endothelium as well as on the basal tonus of vessels from normal and diabetic rats. Indexes about oxidative stress were also determined. We report that the cerebral arteries from diabetic rats show decreased vascular reactivity to acetylcholine (ACh) which was corrected in Pae, DSS, and Pae + DSS treated groups. Furthermore, phenylephrine (PE)-induced contraction response decreased in the treated groups. Phenylephrine and CaCl2-induced vasoconstrictions are partially inhibited in the three treated groups under Ca2+-free medium. Pre-incubated with tetraethylammonium, a non-selective K+ channel blocker, the antagonized relaxation responses increased in DSS and Pae + DSS treated diabetic groups compared with those in diabetic and Pae-treated diabetic groups. In addition, superoxide dismutase activity and thiobarbituric acid reactive substances content significantly changed in the presence of Pae + DSS. We therefore conclude that both Pae and DSS treatments prevent diabetes-induced vascular damage. Furthermore, Pae + DSS prove to be the most efficient treatment regimen. The combination of Pae and DSS produce significant protective effects through the reduction of oxidative stress and through intracellular Ca2+ regulatory mechanisms.
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