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Pulmonary hypertension (PH) is an intractable, severe, and progressive cardiopulmonary disease. Recent findings suggest that human umbilical cord mesenchymal stromal cells (HUCMSCs) and HUCMSC-derived exosomes (HUCMSC-Exos) possess potential therapeutic value for PH. However, whether they have beneficial effects on hypoxic pulmonary hypertension (HPH) is unclear. Exos are released into the extracellular environment by the fusion of intracellular multivesicular bodies with the cell membrane, and they play an important role in cellular communication. Exos ameliorate immune inflammation levels, alter macrophage phenotypes, regulate mitochondrial metabolic function, and inhibit pulmonary vascular remodeling, thereby improving PH. Macrophages are important sources of cytokines and other transmitters and can promote the release of cytokines, vasoactive molecules, and reactive oxygen species, all of which are associated with pulmonary vascular remodeling. Therefore, the aim of this study was to investigate whether HUCMSC-Exos could improve the lung inflammatory microenvironment and inhibit pulmonary vascular remodeling by targeting macrophages and identifying the underlying mechanisms. The results showed that HUCMSC-Exos promoted M2 macrophage polarization, decreased pro-inflammatory factors, increased IL-10 levels, and inhibited IL-33/ST2 axis expression, thereby inhibiting hypoxia-induced proliferation of pulmonary artery smooth muscle cells and ameliorating HPH.
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Exossomos , Hipertensão Pulmonar , Células-Tronco Mesenquimais , Hipertensão Arterial Pulmonar , Humanos , Camundongos , Animais , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Hipertensão Pulmonar/metabolismo , Exossomos/metabolismo , Remodelação Vascular , Cordão Umbilical/metabolismo , Hipóxia/complicações , Hipóxia/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo , Células-Tronco Mesenquimais/metabolismoRESUMO
Hypoxic pulmonary hypertension (HPH) is characterized by progressive pulmonary vasoconstriction, vascular remodeling, and right ventricular hypertrophy, causing right heart failure. This study aimed to investigate the therapeutic effects of exosomes from Tibetan umbilical cord mesenchymal stem cells on HPH via the TGF-ß1/Smad2/3 pathway, comparing them with exosomes from Han Chinese individuals. An HPH rat model was established in vivo, and a hypoxia-induced injury in the rat pulmonary artery smooth muscle cells (rPASMCs) was simulated in vitro. Exosomes from human umbilical cord mesenchymal stem cells were administered to HPH model rats or added to cultured rPASMCs. The therapeutic effects of Tibetan-mesenchymal stem cell-derived exosomes (Tibetan-MSC-exo) and Han-mesenchymal stem cell-derived exosomes (Han-MSC-exo) on HPH were investigated through immunohistochemistry, western blotting, EdU, and Transwell assays. The results showed that Tibetan-MSC-exo significantly attenuated pulmonary vascular remodeling and right ventricular hypertrophy in HPH rats compared with Han-MSC-exo. Tibetan-MSC-exo demonstrated better inhibition of hypoxia-induced rPASMCs proliferation and migration. Transcriptome sequencing revealed upregulated genes (Nbl1, Id2, Smad6, and Ltbp1) related to the TGFß pathway. Nbl1 knockdown enhanced hypoxia-induced rPASMCs proliferation and migration, reversing Tibetan-MSC-exo-induced downregulation of TGFß1 and p-Smad2/3. Furthermore, TGFß1 overexpression hindered the therapeutic effects of Tibetan-MSC-exo and Han-MSC-exo on hypoxic injury. These findings suggest that Tibetan-MSC-exo favors HPH treatment better than Han-MSC-exo, possibly through the modulation of the TGFß1/Smad2/3 pathway via Nbl1.
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Exossomos , Hipertensão Pulmonar , Hipóxia , Células-Tronco Mesenquimais , Remodelação Vascular , Animais , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Remodelação Vascular/fisiologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/terapia , Hipertensão Pulmonar/patologia , Ratos , Hipóxia/metabolismo , Ratos Sprague-Dawley , Masculino , Tibet , Humanos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Fator de Crescimento Transformador beta1/metabolismo , Proliferação de Células , Transdução de Sinais , Modelos Animais de Doenças , Proteína Smad2/metabolismoRESUMO
Uncontrollable dendrite growth and corrosion induced by reactive water molecules and sulfate ions (SO42-) seriously hindered the practical application of aqueous zinc ion batteries (AZIBs). Here we construct artificial solid electrolyte interfaces (SEIs) realized by sodium and calcium bentonite with a layered structure anchored to anodes (NB@Zn and CB@Zn). This artificial SEI layer functioning as a protective coating to isolate activated water molecules, provides high-speed transport channels for Zn2+, and serves as an ionic sieve to repel negatively charged anions while attracting positively charged cations. The theoretical results show that the bentonite electrodes exhibit a higher binding energy for Zn2+. This demonstrates that the bentonite protective layer enhances the Zn-ion deposition kinetics. Consequently, the NB@Zn//MnO2 and CB@Zn//MnO2 full-battery capacities are 96.7 and 70.4 mAh g-1 at 2.0 A g-1 after 1000 cycles, respectively. This study aims to stabilize Zn anodes and improve the electrochemical performance of AZIBs by ion-selection sieving.
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The abnormal expression of protein tyrosine phosphatase 1B (PTP1B) is highly related to several serious human diseases. Therefore, an accurate PTP1B activity assay is beneficial to the diagnosis and treatment of these diseases. In this study, a dual-mode biosensing platform that enabled the sensitive and accurate assay of PTP1B activity was constructed based on the high-frequency (100 MHz) quartz crystal microbalance (QCM) and dual-signaling electrochemical (EC) ratiometric strategy. Covalent-organic framework@gold nanoparticles@ferrocene@single-strand DNA (COF@Au@Fc-S0) was introduced onto the QCM Au chip via the chelation between Zr4+ and phosphate groups (phosphate group of the phosphopeptide (P-peptide) on the QCM Au chip and the phosphate group of thiol-labeled single-stranded DNA (S0) on COF@Au@Fc-S0) and used as a signal reporter. When PTP1B was present, the dephosphorylation of the P-peptide led to the release of COF@Au@Fc-S0 from the QCM Au chip, resulting in an increase in the frequency of the QCM. Meanwhile, the released COF@Au@Fc-S0 hybridized with thiol/methylene blue (MB)-labeled hairpin DNA (S1-MB) on the Au NPs-modified indium-tin oxide (ITO) electrode. This caused MB to be far away from the electrode surface and Fc to be close to the electrode, leading to a decrease in the oxidation peak current of MB and an increase in the oxidation peak current of Fc. Thus, PTP1B-induced dephosphorylation of the P-peptide was monitored in real time by QCM, and PTP1B activity was detected sensitively and reliably using this innovative QCM-EC dual-mode sensing platform with an ultralow detection limit. This platform is anticipated to serve as a robust tool for the analysis of protein phosphatase activity and the discovery of drugs targeting protein phosphatase.
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Técnicas Eletroquímicas , Compostos Ferrosos , Ouro , Estruturas Metalorgânicas , Metalocenos , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Técnicas de Microbalança de Cristal de Quartzo , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/análise , Ouro/química , Humanos , Estruturas Metalorgânicas/química , Compostos Ferrosos/química , Metalocenos/química , DNA de Cadeia Simples/química , DNA de Cadeia Simples/metabolismo , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Zircônio/química , Ensaios Enzimáticos/métodosRESUMO
The detection of lysine acetyltransferases is crucial for diagnosing and treating lung cancer, highlighting the necessity for highly efficient detection methods. We developed a portable, highly accurate, and sensitive technique using fast-scan cyclic voltammetry (FSCV) to determine the activity of the lysine acetyltransferase TIP60, employing a novel miniature electrochemical sensor. This approach involves a compact electrochemical cell, merely 3 mm in diameter, that holds solutions up to 50 µL, equipped with a conductive indium tin oxide working electrode. Uniquely, this system operates on a two-electrode model compatible with the FSCV, obviating the traditional requirement for a reference electrode. The system detects TIP60 activity through the continuous generation of CoA molecules that engage in reactions with Cu(II), thereby significantly improving the accuracy of the acetylation analysis. Remarkably, the detection limit achieved for TIP60 is notably low at 3.3 pg/mL (S/N = 3). The results show that the reversible dynamic acetylation can be effectively regulated by inhibitor incubation and glucose stimulation. This cutting-edge strategy enhances the analysis of a broad spectrum of biomarkers by modifying the responsive unit, and its miniaturization and portability significantly amplify its applicability in biomedical research, promising it to be a versatile tool for early diagnostic and therapeutic interventions in lung cancer.
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Neoplasias Pulmonares , Lisina Acetiltransferases , Humanos , Neoplasias Pulmonares/diagnóstico , Técnicas EletroquímicasRESUMO
Epigenetic modification plays an indispensable role in regulating routine molecular signaling pathways, yet it is rarely used to modulate molecular self-assembly networks. Herein, we constructed a bioorthogonal demethylase-stimulated DNA circuitry (DSC) system for high-fidelity imaging of microRNA (miRNA) in live cells and mice by eliminating undesired off-site signal leakage. The simple and robust DSC system is composed of a primary cell-specific circuitry regulation (CR) module and an ultimate signal-transducing amplifier (SA) module. After the modularly designed DSC system was delivered into target live cells, the DNAzyme of the CR module was site-specifically activated by endogenous demethylase to produce fuel strands for the subsequent miRNA-targeting SA module. Through the on-site and multiply guaranteed molecular recognitions, the lucid yet efficient DSC system realized the reliably amplified in vivo miRNA sensing and enabled the in-depth exploration of the demethylase-involved signal pathway with miRNA in live cells. Our bioorthogonally on-site-activated DSC system represents a universal and versatile biomolecular sensing platform via various demethylase regulations and shows more prospects for more different personalized theragnostics.
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DNA Catalítico , MicroRNAs , MicroRNAs/análise , MicroRNAs/metabolismo , DNA Catalítico/metabolismo , DNA Catalítico/química , Animais , Camundongos , Humanos , Metilação de DNA , Imagem ÓpticaRESUMO
BACKGROUND: Y-box binding protein 1 (YBX1) plays a variety of roles in progression of multiple tumors. However, the role of YBX1 in prognostic value and immune regulation for liver hepatocellular carcinoma (LIHC) remains unclear. The present study aimed to examine the effect of YBX1 on the regulation of tumor immunity and survival prediction in LIHC patients. METHODS: YBX1-related expression profiles and single-cell and bulk sequencing analysis were performed using online databases. YBX1 expression was validated by a quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry. Univariate/multivariate Cox regression analysis was performed to determine independent predictors of overall survival (OS). The ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm and Tumor Immune Dysfunction and Exclusion (TIDE) analysis were used to assess the relationships between YBX1 and LIHC immunity. RESULTS: YBX1 was over-expressed in LIHC tissues and cell lines. High YBX1 expression was significantly associated with poor OS. Univariate/multivariate Cox regression analysis revealed that YBX1 was an independent prognostic factor for LIHC. Gene set enrichment analysis revealed that YBX1 was associated with multiple signaling pathways correlated to LIHC. Additionally, YBX1 was expressed in multiple immune cells and was significantly correlated with immune cells, immune checkpoint markers and tumor immune microenvironment. The TIDE analysis demonstrated that LIHC patients with high YBX1 expression showed a higher T-cell dysfunction score and a higher exclusion score, as well as poorer immunotherapy response. CONCLUSIONS: YBX1 plays crucial oncogenic roles in LIHC and is closely associated with the immune defense system. YBX1 inhibition may serve as a potential treatment for LIHC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Prognóstico , Neoplasias Hepáticas/genética , Algoritmos , Microambiente Tumoral/genética , Proteína 1 de Ligação a Y-Box/genéticaRESUMO
MAIN CONCLUSION: In this study, six ZaBZRs were identified in Zanthoxylum armatum DC, and all the ZaBZRs were upregulated by abscisic acid (ABA) and drought. Overexpression of ZaBZR1 enhanced the drought tolerance of transgenic Nicotiana benthamian. Brassinosteroids (BRs) are a pivotal class of sterol hormones in plants that play a crucial role in plant growth and development. BZR (brassinazole resistant) is a crucial transcription factor in the signal transduction pathway of BRs. However, the BZR gene family members have not yet been identified in Zanthoxylum armatum DC. In this study, six members of the ZaBZR family were identified by bioinformatic methods. All six ZaBZRs exhibited multiple phosphorylation sites. Phylogenetic and collinearity analyses revealed a closest relationship between ZaBZRs and ZbBZRs located on the B subgenomes. Expression analysis revealed tissue-specific expression patterns of ZaBZRs in Z. armatum, and their promoter regions contained cis-acting elements associated with hormone response and stress induction. Additionally, all six ZaBZRs showed upregulation upon treatment after abscisic acid (ABA) and polyethylene glycol (PEG), indicating their participation in drought response. Subsequently, we conducted an extensive investigation of ZaBZR1. ZaBZR1 showed the highest expression in the root, followed by the stem and terminal bud. Subcellular localization analysis revealed that ZaBZR1 is present in the cytoplasm and nucleus. Overexpression of ZaBZR1 in transgenic Nicotiana benthamiana improved seed germination rate and root growth under drought conditions, reducing water loss rates compared to wild-type plants. Furthermore, ZaBZR1 increased proline content (PRO) and decreased malondialdehyde content (MDA), indicating improved tolerance to drought-induced oxidative stress. The transgenic plants also showed a reduced accumulation of reactive oxygen species. Importantly, ZaBZR1 up-regulated the expression of drought-related genes such as NbP5CS1, NbDREB2A, and NbWRKY44. These findings highlight the potential of ZaBZR1 as a candidate gene for enhancing drought resistance in transgenic N. benthamiana and provide insight into the function of ZaBZRs in Z. armatum.
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Secas , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas , Plantas Geneticamente Modificadas , Zanthoxylum , Plantas Geneticamente Modificadas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Zanthoxylum/genética , Zanthoxylum/fisiologia , Zanthoxylum/metabolismo , Nicotiana/genética , Nicotiana/fisiologia , Nicotiana/efeitos dos fármacos , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Família Multigênica , Brassinosteroides/metabolismo , Brassinosteroides/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico/genética , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Resistência à SecaRESUMO
The EP300-ZNF384 fusion gene is an oncogenic driver in B-cell acute lymphoblastic leukemia (B-ALL). In the present study, we demonstrated that EP300-ZNF384 substantially induces the transcription of IL3RA and the expression of IL3Rα (CD123) on B-ALL cell membranes. Interleukin 3 (IL-3) supplementation promotes the proliferation of EP300-ZNF348-positive B-ALL cells by activating STAT5. Conditional knockdown of IL3RA in EP300-ZF384-positive cells inhibited the proliferation in vitro, and induced a significant increase in overall survival of mice, which is attributed to impaired propagation ability of leukemia cells. Mechanistically, the EP300-ZNF384 fusion protein transactivates the promoter activity of IL3RA by binding to an A-rich sequence localized at -222/-234 of IL3RA. Furthermore, forced EP300-ZNF384 expression induces the expression of IL3Rα on cell membranes and the secretion of IL-3 in CD19-positive B precursor cells derived from healthy individuals. Doxorubicin displayed a selective killing of EP300-ZNF384-positive B-ALL cells in vitro and in vivo. Collectively, we identify IL3RA as a direct downstream target of EP300-ZNF384, suggesting CD123 is a potent biomarker for EP300-ZNF384-driven B-ALL. Targeting CD123 may be a novel therapeutic approach to EP300-ZNF384-positive patients, alternative or, more likely, complementary to standard chemotherapy regimen in clinical setting.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Transativadores , Animais , Humanos , Camundongos , Doxorrubicina , Proteína p300 Associada a E1A , Interleucina-3 , Subunidade alfa de Receptor de Interleucina-3 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Transativadores/metabolismoRESUMO
This article explores the asymmetric Michael addition reaction of 2-hydroxy-1,4-naphthoquinone and indole-3-ones catalyzed by cinchona alkaloids. This strategy utilizes 2-hydroxy-1,4-naphthoquinone and easily prepared indole-3-one as substrates, resulting in the synthesis of 23 unprecedented indolin-3-ones bearing a 1,4-naphthoquinone unit at the C2 position of indole under simple and mild reaction conditions, with up to 88% yield, 98% ee, and >20:1 dr.
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BACKGROUND AND AIM: Hydronidone (HDD) is a novel pirfenidone derivative developed initially to reduce hepatotoxicity. Our previous studies in animals and humans have demonstrated that HDD treatment effectively attenuates liver fibrosis, yet the underlying mechanism remains unclear. This study aimed to investigate whether HDD exerts its anti-fibrotic effect by inducing apoptosis in activated hepatic stellate cells (aHSCs) through the endoplasmic reticulum stress (ERS)-associated mitochondrial apoptotic pathway. METHODS: The carbon tetrachloride (CCl4)- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis models were used for in vivo studies. In vitro studies were conducted using the human hepatic stellate cell line LX-2. The apoptotic effect of HDD on aHSCs was examined using TUNEL and flow cytometry assays. The small interfering RNA (siRNA) technique was employed to downregulate the expression of interest genes. RESULTS: HDD treatment significantly promoted apoptosis in aHSCs in both the CCl4- and DDC-induced liver fibrosis in mice and LX-2 cells. Mechanistic studies revealed that HDD triggered ERS and subsequently activated the IRE1α-ASK1-JNK pathway. Furthermore, the influx of cytochrome c from the mitochondria into the cytoplasm was increased, leading to mitochondrial dysfunction and ultimately triggering apoptosis in aHSCs. Notably, inhibition of IRE1α or ASK1 by siRNA partially abrogated the pro-apoptotic effect of HDD in aHSCs. CONCLUSIONS: The findings of both in vivo and in vitro studies suggest that HDD induces apoptosis in aHSCs via the ERS-associated mitochondrial apoptotic pathway, potentially contributing to the amelioration of liver fibrosis.
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Apoptose , Estresse do Retículo Endoplasmático , Células Estreladas do Fígado , Cirrose Hepática , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Animais , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/induzido quimicamente , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Endorribonucleases/metabolismo , Endorribonucleases/genética , Tetracloreto de Carbono , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Masculino , Linhagem Celular , Piridonas/farmacologia , Camundongos , MAP Quinase Quinase Quinase 5/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacosRESUMO
Based on the crucial role of histone deacetylase (HDAC) and receptor tyrosine kinase in angiogenesis, in situ assembly, skeletal transition, molecular hybridization, and pharmacophore fusion were employed to yield seventy-six multi-target angiogenesis inhibitors. Biological evaluation indicated that most of the compounds exhibited potent proliferation inhibitory activity on MCF-7 cells, with the TH series having the highest inhibitory activity on MCF-7 cells. In addition, the IC50 values of TA11 and TH3 against HT-29 cellswere 0.078 µmol/L and 0.068 µmol/L, respectively. The cytotoxicity evaluation indicated that TC9, TA11, TM4, and TH3 displayed good safety against HEK293T cells. TH2 and TH3 could induce apoptosis of MCF-7 cells. Molecular modeling and ADMET prediction results indicated that most of target compounds showed promising medicinal properties, which was consistent with the experimental results. Our findings provided new lead compounds for the structural optimization of multi-target angiogenesis inhibitors.
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Inibidores da Angiogênese , Antineoplásicos , Humanos , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Inibidores da Angiogênese/farmacologia , Angiogênese , Células HEK293 , Inibidores de Histona Desacetilases/química , Ensaios de Seleção de Medicamentos Antitumorais , Desenho de Fármacos , Simulação de Acoplamento Molecular , Antineoplásicos/química , Proliferação de CélulasRESUMO
In recent years, targeting tumor angiogenesis has emerged as a prominent research focus in the treatment and prevention of tumor expansion. A7R (ATWLPPR) exhibits high affinity and specificity for VEGFR-2, which is overexpressed in various tumors. To enhance the tumor tissue and cell penetration capabilities of A7R, we substituted its non-critical amino acid with Arginine (R) and Glutamic acid (E), cyclized the mutant peptide, and linked it to the membrane permeation sequence using coordination principles. We designed and synthesized fifteen novel penetrating peptides that target tumor blood vessels and cells, followed by conducting various biological evaluations and cell imaging experiments. The results demonstrated that Cyclo-A7R-RRR and A7R-RLLRLLR exhibited excellent permeability towards tumor cells, with Cyclo-A7R-RRR showing superior serum stability compared to A7R. Furthermore, the modified peptides showed no toxicity towards HeLa cells, U251 cells, HuH-7 cells, and HEK293 cells under 10 µmol/L. Utilizing Cyclo-A7R-RRR or A7R-RLLRLLR for transmembrane delivery of drug molecules could significantly improve their efficacy. Our findings broaden the potential application scenarios of A7R in targeted tumor angiogenesis.
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Sistemas de Liberação de Medicamentos , Glioma , Humanos , Glioma/tratamento farmacológico , Células HeLa , Células HEK293 , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Linhagem Celular TumoralRESUMO
Histone acetylation modifications in filamentous fungi play a crucial role in epigenetic gene regulation and are closely linked to the transcription of secondary metabolite (SM) biosynthetic gene clusters (BGCs). Histone deacetylases (HDACs) play a pivotal role in determining the extent of histone acetylation modifications and act as triggers for the expression activity of target BGCs. The genus Chaetomium is widely recognized as a rich source of novel and bioactive SMs. Deletion of a class I HDAC gene of Chaetomium olivaceum SD-80A, g7489, induces a substantial pleiotropic effect on the expression of SM BGCs. The C. olivaceum SD-80A ∆g7489 strain exhibited significant changes in morphology, sporulation ability, and secondary metabolic profile, resulting in the emergence of new compound peaks. Notably, three polyketides (A1-A3) and one asterriquinone (A4) were isolated from this mutant strain. Furthermore, our study explored the BGCs of A1-A4, confirming the function of two polyketide synthases (PKSs). Collectively, our findings highlight the promising potential of molecular epigenetic approaches for the elucidation of novel active compounds and their biosynthetic elements in Chaetomium species. This finding holds great significance for the exploration and utilization of Chaetomium resources. KEY POINTS: ⢠Deletion of a class I histone deacetylase activated secondary metabolite gene clusters. ⢠Three polyketides and one asterriquinone were isolated from HDAC deleted strain. ⢠Two different PKSs were reported in C. olivaceum SD-80A.
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Chaetomium , Histona Desacetilases , Família Multigênica , Policetídeos , Metabolismo Secundário , Chaetomium/genética , Chaetomium/enzimologia , Chaetomium/metabolismo , Metabolismo Secundário/genética , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Policetídeos/metabolismo , Deleção de Genes , Regulação Fúngica da Expressão Gênica , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Vias Biossintéticas/genética , Epigênese GenéticaRESUMO
PURPOSE: Enhanced recovery after surgery (ERAS) was characterized as patient-centered, evidence-based, multidisciplinary team-developed routes for a surgical speciality and institution to improve postoperative recovery and attenuate the surgical stress response. However, evidence of their effectiveness in osteoarthroplasty remains sparse. This study aimed to develop an ERAS standard and evaluate the significance of ERAS interventions for postoperative outcomes after primary total hip arthroplasty (THA) or total knee arthroplasty (TKA). METHODS: We searched Medline, Embase, Cochrane databases, and Clinicaltrials.gov for randomized controlled trials, cohort studies, and case-control studies until 24 February 2023. All relevant data were collected from studies meeting the inclusion criteria. Two reviewers independently assessed the risk of bias and extracted data. The primary outcome was the length of stay (LOS), postoperative complications, and readmission rate. The secondary outcomes included transfusion rate, mortality rate, visual analog score (VAS), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Short Form 36 (SF-36) bodily pain (SF-36 BP), SF-36 physical function (SF-36 PF), oxford knee score, and range of motion (ROM). RESULTS: A total of 47 studies involving 76 971 patients (ERAS group: 29 702, control group: 47 269) met the inclusion criteria and were included in the meta-analysis. The result showed that ERAS could significantly shorten the LOS (WMD = -2.65, P < .001), reduce transfusion rate (OR = 0.40, P < .001), and lower 30-day postoperative mortality (OR = 0.46, P = .01) without increasing postoperative complications or readmission rate. Apart from that, ERAS may decrease patients' VAS (WMD = -0.88, P = .01) while improving their ROM (WMD = 6.65, P = .004), SF-36 BP (WMD = 4.49, P < .001), and SF-36 PF (WMD = 3.64, P < .001) scores. However, there was no significant difference in WOMAC, oxford knee score between the ERAS and control groups.Furthermore, we determined that the following seven components of the ERAS program are highly advised: avoid bowel preparation, PONV prophylaxis, standardized anesthesia, use of local anesthetics for infiltration analgesia and nerve blocks, tranexamic acid, prevent hypothermia, and early mobilization. CONCLUSION: Our meta-analysis suggested that the ERAS could significantly shorten the LOS, reduce transfusion rate, and lower 30-day postoperative mortality without increasing postoperative complications or readmission rate after THA and TKA. Meanwhile, ERAS could decrease the VAS of patients while improving their ROM, SF-36 BP, and SF-36 PF scores. Finally, we expect future studies to utilize the seven ERAS elements proposed in our meta-analysis to prevent increased readmission rate for patients with THA or TKA.
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Artroplastia de Quadril , Artroplastia do Joelho , Recuperação Pós-Cirúrgica Melhorada , Tempo de Internação , Complicações Pós-Operatórias , Humanos , Complicações Pós-Operatórias/prevenção & controle , Recuperação de Função Fisiológica , Readmissão do Paciente/estatística & dados numéricos , Amplitude de Movimento ArticularRESUMO
BACKGROUND: The treatment of completely displaced midshaft clavicle fractures is still controversial, especially Robinson 2B fractures. Titanium elastic nail (TEN) fixation is a good option for simple fractures, but no reports exist on its use in complex fractures. This study aimed to present a surgical method using the Nice knot-assisted TEN fixation to treat Robinson 2B midshaft clavicular fractures. METHODS: A retrospective analysis of 29 patients who underwent fixation with TEN and had a 1-year postoperative follow-up between 2016 and 2020 was performed. The fractures were classified as Robinson type 2B1 in 17 cases and type 2B2 in 12 cases. Length of the incision, postoperative shoulder function Disability of Arm Shoulder and Hand (DASH) score and Constant score, complications rate, and second surgical incision length were recorded. RESULTS: The length of the incision was 2-6 cm (average 3.7 cm). All incisions healed by first intention, and no infection or nerve injury occurred. The Constant score was 92-100 (average 96) and the DASH score was 0-6.2 (mean, 2.64). TEN bending and hypertrophic nonunion occurred in one case (3.4%) and implant irritation occurred in four cases (13.8%) Fixation implants were removed at 12-26 months (mean, 14.6 months) after surgery, and the length of the second incision was 1-2.5 cm (average 1.3 cm). CONCLUSIONS: Intramedullary fixation by TEN is approved as a suitable surgical technique in clavicular fracture treatment. Nice knot-assisted fixation provides multifragmentary fracture stabilization, contributing to good fracture healing. Surgeons should consider this technique in treating Robinson 2B midshaft clavicular fractures. TRIAL REGISTRATION: Retrospectively registered. This study was approved by the Ethics Committee of Wuxi Ninth People's Hospital (LW20220021).
Assuntos
Fixação Intramedular de Fraturas , Fraturas Ósseas , Humanos , Titânio , Clavícula/diagnóstico por imagem , Clavícula/cirurgia , Clavícula/lesões , Estudos Retrospectivos , Resultado do Tratamento , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Consolidação da Fratura/fisiologia , Fixação Intramedular de Fraturas/métodos , Placas Ósseas , Fixação Interna de Fraturas/efeitos adversosRESUMO
Objective: Exploring the clinical efficacy of neomycin and sakubactria valsartan in the treatment of patients with chronic heart failure (CHF) and atrial fibrillation. This study investigates the potential benefits of combining neomycin with sakubactria valsartan, a medication with a background of demonstrated efficacy in cardiovascular conditions, to address the complex challenges presented by chronic heart failure and atrial fibrillation. Methods: Using a single-center clinical randomized trial, 111 patients with CHF complicated with atrial fibrillation who were treated in the cardiovascular department of Xingtai Third Hospital from June 2019 to March 2021 were randomly divided into two groups. In the control group, 56 patients received treatment with Western Medicine Foundation + Shakubatra valsartan. In the experimental group, consisting of 55 patients, the treatment was identical to the control group, with the additional administration of neomycin.. After 12 weeks of continuous treatment, the echocardiograms, electrocardiogram parameters, and Differences in changes in serum soluble growth stimulating gene 2 protein (sST2) and galactose agglutinin 3 (Gal-3), clinical efficacy, and incidence of adverse reactions. Results: Before treatment, no significant differences existed in LVEF, LVEDV, FS, and SV between the experimental and control groups (P > .05). Post-treatment, both groups exhibited significant improvements in these parameters, with the experimental group showing statistically higher values (P < .05).Similarly, pre-treatment comparisons of Pd, sST2, Gal-3, and NT-proBNP revealed no significant differences between the groups (P > .05). After treatment, both groups showed significant reductions, with the experimental group demonstrating lower values (P < .05).Clinical efficacy assessment post-treatment showed significant differences. The experimental group had a basic cure rate of 45.45%, a significant effective rate of 43.64%, and an effective rate of 10.91%, while the control group had rates of 28.57%, 48.21%, and 23.21%, respectively (P < .05).Adverse reactions occurred in 9 and 4 patients in the experimental and control groups, respectively. The severity was not significant, and treatment was uninterrupted (P > 0.05).The treatment improved heart function and reduced atrial fibrillation occurrences, holding clinical significance by potentially enhancing patients' quality of life and decreasing cardiovascular events. These results highlight the clinical significance of this treatment, which may help improve patients' quality of life and reduce the occurrence of cardiovascular events. Conclusion: The treatment of patients with CHF combined with atrial fibrillation using neomycin and sakubactria valsartan can more effectively improve their cardiac function and alleviate the condition of atrial fibrillation, which is worthy of clinical promotion and application. In actual clinical practice, physicians and healthcare providers may consider incorporating this treatment into their treatment regimens, especially for patients who need to improve heart function and reduce the risk of atrial fibrillation. Additionally, further research and clinical trials can further validate these findings to ensure their effectiveness and safety. These insights will help the medical community better understand how to apply this treatment to real patients and maximize its clinical effectiveness.
RESUMO
6:2 Chlorinated polyfluoroalkyl ether sulfonate (F-53B) is a new type of perfluorinated and polyfluoroalkyl substance (PFAS) that is used extensively in industry and manufacturing. F-53B causes damage to multiple mammalian organs. However, the impacts of F-53B on bone are unknown. Maternal exposure to F-53B is of particular concern because of the vulnerability of the developing fetus and newborn to contaminants from the mother. The goal of this study was to examine the impacts of maternal F-53B exposure on bone growth and development in offspring and to explore its underlying mechanisms. Herein, C57BL/6â¯J mice were given free access to deionized water containing 0, 0.57, or 5.7â¯mg/L F-53B during pregnancy and lactation. F-53B exposure resulted in impaired liver function, decreased IGF-1 secretion, dysregulation of bone metabolism and disruption of the dynamic balance between osteoblasts and osteoclasts in male offspring. F-53B inhibits longitudinal bone growth and development and causes osteoporosis in male offspring. F-53B may affect the growth and development of offspring bone via the IGF-1/OPG/RANKL/CTSK signaling pathway. This study provides new insights for the study of short stature and bone injury caused by F-53B.
Assuntos
Desenvolvimento Ósseo , Lactação , Exposição Materna , Camundongos Endogâmicos C57BL , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Masculino , Gravidez , Camundongos , Exposição Materna/efeitos adversos , Desenvolvimento Ósseo/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Fluorocarbonos/toxicidade , Osteoprotegerina/metabolismo , Osteoclastos/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Ácidos Sulfônicos/toxicidadeRESUMO
Cadmium (Cd) pollutes 7.0â¯% of China's land area. This study examined the potential of Houttuynia cordata for Cd phytoremediation because of its ability to accumulate Cd in its growth matrix. H. cordata were planted in plastic pots filled with paddy field soils having low (LCd), medium (MCd), and high (HCd) Cd levels of 0.19, 0.69, and 2.91â¯mg/kg, respectively. After six months of growth, harvested plant parts were evaluated for Cd uptake and tolerance mechanisms. Metabolomics and metagenomics approaches were employed to investigate the soil rhizosphere mechanism. Results showed that the average plant biomass increased as soil Cd increased. The biomass Cd contents surpassed the allowable Cd limits for food (≤ 0.2â¯mg/kg) and medicinal uses (≤ 0.3â¯mg/kg). Cd contents were higher in H. cordata roots (30.59-86.27â¯mg/kg) than in other plant parts (0.63-2.90â¯mg/kg), with significantly increasing values as Cd soil level increased. Phenolic acids, lipids, amino acids and derivatives, organic acids, and alkaloids comprised the majority (69â¯in MCd vs HCd and 73â¯% in LCd vs HCd) of the shared upregulated metabolites. In addition, 13 metabolites specific to H. cordata root exudates were significantly increased. The top two principal metabolic pathways were arginine and proline metabolism, and beta-alanine metabolism. H. cordata increased the abundance of Firmicutes and Glomeromycota across all three Cd levels, and also stimulated the growth of Patescibacteria, Rozellomycota, and Claroideoglomus in HCd. Accordingly, H. cordata demonstrated potential for remediation of Cd-contaminated soils, and safety measures for its production and food use must be highly considered.
Assuntos
Biodegradação Ambiental , Cádmio , Houttuynia , Rizosfera , Poluentes do Solo , Cádmio/metabolismo , Cádmio/análise , Poluentes do Solo/metabolismo , China , Raízes de Plantas/metabolismo , Solo/química , BiomassaRESUMO
Psychrophilic fungus Pseudogymnoascus sp. OUCMDZ-4032 derived from Antarctica was cultivated under 16 °C to produce a new glucolipid compound (1). Its structure was elucidated by analysis of detailed spectroscopic data, acid hydrolysis and 1-phenyl-3-methyl-5-pyrazolone precolumn derivatization, and 13C NMR quantum chemical calculations. Though compound 1 did not show inhibitory activity against bacteria, it can reduce the minimum inhibitory concentration (MIC) of ciprofloxacin against Gram-negative bacteria Pseudomonas aeruginosa, Escherichia coli, and Salmonella paratyphi by 1024, 256 and 256-fold. Compound 1 showed potential as a synergistically inhibiting adjuvant in co-administration with antibiotic to enhance antibacterial activities.