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1.
J Environ Manage ; 356: 120633, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38513579

RESUMO

Although straw returning combined with blended controlled-release urea fertilizer (BUFS) has been shown to improve wheat-maize rotation system productivity, their effects on greenhouse gas (GHG) emissions, carbon footprints (CF), and net ecosystem economic benefits (NEEB) are still unknown. Life cycle assessment was used to investigate a long-term (2013-2022) wheat-maize rotation experiment that included straw combined with two N fertilizer types [BUFS and (conventional urea fertilizer) CUFS] and straw-free treatments (BUF and CUF). The results showed that BUFS and CUFS treatments increased the annual yield by 13.8% and 11.5%, respectively, compared to BUF and CUF treatments. The BUFS treatment increased the yearly yield by 13.8% compared to the CUFS treatment. Since BUFS and CUFS treatments increased soil organic carbon (SOC) sink sequestration by 25.0% and 27.0% compared to BUF and CUF treatments, they reduced annual GHG emissions by 7.1% and 4.7% and CF per unit of yield (CFY) by 13.7% and 9.6%, respectively. BUFS treatment also increased SOC sink sequestration by 20.3%, reduced GHG emissions by 10.7% and CFY by 23.0% compared to CUFS treatment. It is worth noting that the BUFS and CUFS treatments increased the annual ecological costs by 41.6%, 26.9%, and health costs by 70.1% and 46.7% compared to the BUF and CUF treatments, but also increased the net yield benefits by 9.8%, 6.8%, and the soil nutrient cycling values by 29.2%, 27.3%, and finally improved the NEEB by 10.1%, 7.3%, respectively. Similar results were obtained for the BUFS treatment compared to the CUFS treatment, ultimately improving the NEEB by 23.1%. Based on assessing yield, GHG emissions, CF, and NEEB indicators, the BUFS treatment is recommended as an ideal agricultural fertilization model to promote sustainable and clean production in the wheat-maize rotation system and to protect the agroecological environment.


Assuntos
Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Solo , Fertilizantes , Carbono/análise , Ecossistema , Preparações de Ação Retardada , Agricultura/métodos , Zea mays , Triticum , China , Óxido Nitroso/análise
2.
Science ; 383(6689): eadj4591, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38513023

RESUMO

Brassinosteroids are steroidal phytohormones that regulate plant development and physiology, including adaptation to environmental stresses. Brassinosteroids are synthesized in the cell interior but bind receptors at the cell surface, necessitating a yet to be identified export mechanism. Here, we show that a member of the ATP-binding cassette (ABC) transporter superfamily, ABCB19, functions as a brassinosteroid exporter. We present its structure in both the substrate-unbound and the brassinosteroid-bound states. Bioactive brassinosteroids are potent activators of ABCB19 ATP hydrolysis activity, and transport assays showed that ABCB19 transports brassinosteroids. In Arabidopsis thaliana, ABCB19 and its close homolog, ABCB1, positively regulate brassinosteroid responses. Our results uncover an elusive export mechanism for bioactive brassinosteroids that is tightly coordinated with brassinosteroid signaling.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Proteínas de Arabidopsis , Arabidopsis , Brassinosteroides , Trifosfato de Adenosina/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transportadores de Cassetes de Ligação de ATP/química , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Brassinosteroides/metabolismo , Ácidos Indolacéticos/metabolismo , Conformação Proteica
3.
Anal Bioanal Chem ; 416(8): 1883-1906, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367042

RESUMO

In this paper, we establish an in situ visualization analysis method to image the spatial distribution of metabolites in different parts (sclerotium, coremium) and different microregions of Cordyceps cicadae (C. cicadae) to achieve the in situ visual characterization of tissues for a variety of metabolites such as nucleosides, amino acids, polysaccharides, organic acids, fatty acids, and so on. The study included LC-MS chemical composition identification, preparation of C. cicadae tissue sections, DEDI-MSI analysis, DESI combined with Q-TOF/MS to obtain high-resolution imaging of mass-to-charge ratio and space, imaging of C. cicadae in positive-negative ion mode with a spatial resolution of 100 µm, and localizing and identifying its chemical compositions based on its precise mass. A total of 62 compounds were identified; nucleosides were mainly distributed in the coremium, L-threonine and DL-isoleucine, and other essential amino acids; peptides were mainly distributed in the sclerotium of C. cicadae; and the rest of the amino acids did not have a clear pattern; sugars and sugar alcohols were mainly distributed in the coremium of C. cicadae; organic acids and fatty acids were distributed in the nucleus of C. cicadae more than in the sclerotium, and the mass spectrometry imaging method is established in the research. The mass spectrometry imaging method established in this study is simple and fast and can visualize and analyse the spatial distribution of metabolites of C. cicadae, which is of great significance in characterizing the metabolic network of C. cicadae, and provides support for the quality evaluation of C. cicadae and the study of the temporal and spatial metabolic network of chemical compounds.


Assuntos
Cordyceps , Distribuição Tecidual , Espectrometria de Massas , Cordyceps/química , Cordyceps/metabolismo , Nucleosídeos/química , Ácidos Graxos/metabolismo , Aminoácidos/metabolismo , Espectrometria de Massas por Ionização por Electrospray/métodos
4.
J Pharm Pharmacol ; 76(3): 236-244, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38183672

RESUMO

OBJECTIVES: The mechanisms underlying the therapeutic effects of Si-Zhi Wan (SZW), a traditional Chinese medicine used to treat osteoporosis (OP), remain unknown. This study investigated the therapeutic effects of SZW on mice that underwent ovariectomy (OVX) and underlying mechanisms thereof. METHODS: We established an in vivo model of OP by performing OVX in mice. Microcomputed tomography (Micro-CT) was used to assess changes in bone characteristics of mice following SZW administration for 4 weeks. H&E staining revealed alterations in bone tissues of mice. Osteoclastogenesis in mouse bone tissue was observed using tartrate-resistant acid phosphatase staining and western blotting. Furthermore, we examined the impact of SZW on osteoclastogenesis in vitro using receptor activator of nuclear factor kappa-B ligand (RANKL). Finally, we explored the regulatory effects of SZW on osteoclast autophagy and the AMPK pathway. KEY FINDINGS: The results demonstrated that high-dose SZW reversed changes in bone density parameters caused by OVX, including bone volume (BV), BV/total volume, trabecular number, and trabecular spacing (P = 0.0007, 0.0035, 0.0114, and 0.0182, respectively), and stimulated the formation of bone trabeculae in mice (P < 0.0001). Furthermore, SZW suppressed osteoclast formation in mice with OVX and inhibited osteoclast formation induced by RANKL. Mechanistically, SZW inhibited osteoclast precursor cell autophagy through the AMPK pathway. CONCLUSIONS: SZW effectively inhibited the autophagy of osteoclast precursors by regulating the AMPK pathway, thereby exerting anti-osteoclastogenic effects and serving as an alternative therapy for OP.


Assuntos
Osteoclastos , Osteoporose , Feminino , Camundongos , Animais , Humanos , Osteoclastos/metabolismo , Osteogênese , Proteínas Quinases Ativadas por AMP/metabolismo , Microtomografia por Raio-X , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Transdução de Sinais , Autofagia , Ligante RANK/metabolismo , Ligante RANK/farmacologia , Ligante RANK/uso terapêutico , Ovariectomia , Diferenciação Celular
5.
Research (Wash D C) ; 7: 0304, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38269028

RESUMO

Mixtures of active self-propelled and passive colloidal particles promise rich assembly and dynamic states that are beyond reach via equilibrium routes. Yet, controllable transition between different dynamic states remains rare. Here, we reveal a plethora of dynamic behaviors emerging in assemblies of chemically propelled snowman-like active colloids and passive spherical particles as the particle shape, size, and composition are tuned. For example, assembles of one or more active colloids with one passive particle exhibit distinct translating or orbiting states while those composed of one active colloid with 2 passive particles display persistent "8"-like cyclic motion or hopping between circling states around one passive particle in the plane and around the waist of 2 passive ones out of the plane, controlled by the shape of the active colloid and the size of the passive particles, respectively. These morphology-tailored dynamic transitions are in excellent agreement with state diagrams predicted by mesoscale dynamics simulations. Our work discloses new dynamic states and corresponding transition strategies, which promise new applications of active systems such as micromachines with functions that are otherwise impossible.

6.
Nat Chem Biol ; 20(1): 74-82, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37580554

RESUMO

G-protein-coupled receptors (GPCRs) are a class of integral membrane proteins that detect environmental cues and trigger cellular responses. Deciphering the functional states of GPCRs induced by various ligands has been one of the primary goals in the field. Here we developed an effective universal method for GPCR cryo-electron microscopy structure determination without the need to prepare GPCR-signaling protein complexes. Using this method, we successfully solved the structures of the ß2-adrenergic receptor (ß2AR) bound to antagonistic and agonistic ligands and the adhesion GPCR ADGRL3 in the apo state. For ß2AR, an intermediate state stabilized by the partial agonist was captured. For ADGRL3, the structure revealed that inactive ADGRL3 adopts a compact fold and that large unusual conformational changes on both the extracellular and intracellular sides are required for activation of adhesion GPCRs. We anticipate that this method will open a new avenue for understanding GPCR structure‒function relationships and drug development.


Assuntos
Receptores Adrenérgicos beta 2 , Receptores Acoplados a Proteínas G , Modelos Moleculares , Microscopia Crioeletrônica , Receptores Acoplados a Proteínas G/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Ligantes
7.
Soft Matter ; 19(48): 9505-9510, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38044703

RESUMO

The organization of microscopic objects into specific structures with movable parts is a prerequisite for building sophisticated micromachines with complex functions, as exemplified by their macroscopic counterparts. Here we report the self-assembly of active and passive colloids into micromachinery with passive rotational parts. Depending on the attachment of the active colloid to a substrate, which varies the degrees of free freedom of the assembly, colloidal machines with rich internal rotational dynamics are realized. Energetic analysis reveals that the energy efficiency increases with the degrees of freedom of the machine. The experimental results can be rationalized by the cooperation of phoretic interaction and osmotic flow encoded in the shape of the active colloid, which site-specifically binds and exerts a torque to passive colloids, supported by finite element calculations and mesoscale simulations. Our work offers a new design principle that utilizes nonequilibrium interfacial phenomena for spontaneous construction of multiple-component reconfigurable micromachinery.

8.
BMC Complement Med Ther ; 23(1): 437, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049800

RESUMO

CONTEXT: Inflammation has been identified as a key factor contributing to the development of numerous diseases. Several anti-inflammatory drugs have been developed to treat inflammation-related diseases. However, some of such drugs are associated with varying degrees of side effects. Therefore, it is imperative to develop new anti-inflammatory drugs with reducing side effects for the treatment of inflammation-related diseases. Natural anti-inflammatory drugs have emerged as an important area of research in recent years. The study was to determine the anti-inflammatory mechanism of Paridis rhizoma extract (PRE) in rat models of acute inflammation induced by carrageenan and RAW264.7 cells models induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: PRE was investigated using the carrageenan-induced paw oedema model on rats in vivo. Histopathology examined the extent of inflammatory infiltration and tissue damage. The effect of PRE on the levels of specific cytokines was determined using enzyme-linked immunosorbent assay (ELISA). The Cell Counting Kit (CCK)-8 assay evaluated the cytotoxic effects of PRE on Raw264.7 cells. The mRNA expression levels of cytokines were quantified using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Western blot measured TNF-α, IL6, TLR4, p-P65, p-IKB, HO1, SOD1 and SOD2. Fluorescence measured the cellular levels of reactive oxygen species (ROS). RESULTS: PRE treatment reduced interstitial edema and structural damage in a dose-dependent manner in vivo. PRE inhibited inflammatory responses in vivo and in vitro, as evidenced by the decreased expression of inflammatory factors, production of ROS, and increased expression of SOD1, SOD2, and HO1. Moreover, PRE inhibited the activity of the nuclear factor kappa B (NF-kB) pathway. CONCLUSION: The anti-inflammatory activity and potential mechanism of PRE were demonstrated according to the results. PRE reduced LPS-induced inflammation in RAW264.7 cells by inhibiting the NF-KB signaling pathway and ROS production in vitro. PRE alleviated interstitial edema and structural damage in the carrageenan-induced paw edema model on rats in vivo. This study provided an idea for future development of PR-based anti-inflammatory drugs.


Assuntos
NF-kappa B , Extratos Vegetais , Ratos , Animais , Carragenina/efeitos adversos , Extratos Vegetais/uso terapêutico , NF-kappa B/metabolismo , Etanol/química , Espécies Reativas de Oxigênio , Lipopolissacarídeos/efeitos adversos , Superóxido Dismutase-1/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Edema/tratamento farmacológico , Edema/induzido quimicamente
9.
J Voice ; 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37880051

RESUMO

OBJECTIVES: The effectiveness of deep brain stimulation (DBS) in treating vocal tremors is currently a subject of debate. To assess the efficacy of DBS therapy in adults with vocal tremors (VT), we analyzed its impact on voice tremor severity, voice-related quality of life, fundamental frequency, voice intensity, and emotional state. METHODS: We conducted a systematic review with meta-analysis to investigate the impact of DBS therapy on voice tremor severity, voice-related quality of life, fundamental frequency, voice intensity, and emotional state in adults with vocal tremors (PROSPERO/CRD42023420272). The PubMed, Embase, Cochrane Library, Cochrane Central Register of Controlled Trials databases were searched up to September 20, 2022. Primary outcome measures included voice tremor severity and voice-related quality of life (V-RQOL), while fundamental frequency (F0) and voice intensity, along with emotional state, were selected as secondary outcome indicators. We employed the Cochrane Collaboration's tool for assessing bias risk in randomized trials. Meta-analysis (standardized difference of means and weighted mean differences) and heterogeneity analysis (I2) were performed. RESULTS: Our search identified 1186 studies, of which nine studies involving 61 patients met the inclusion criteria. The severity of voice tremor (SMD = -1.08; 95% CI: -1.80 to 0.35; P = 0.02) and V-RQOL (SMD = -1.39; 95% CI: -2.68 to -0.09; P = 0.04) in patients with vocal tremor significantly improved after DBS "on". Subgroup analyses revealed that the stimulation site may contribute to high heterogeneity. Specifically, Vim DBS showed significant improvement in voice tremor severity (SMD = -0.97; 95% CI: -1.84 to -0.09; I2 = 51.01%), while STN DBS did not demonstrate a clear benefit in addressing vocal tremor. There was no significant difference between DBS "on" and DBS "off" in terms of F0, voice intensity, or emotional status. CONCLUSION: DBS therapy is effective in enhancing voice quality and voice-related quality of life in patients with vocal tremors. Notably, Vim DBS demonstrates a significant improvement in voice tremor severity, particularly in VT patients with ET and SD.

10.
Nat Plants ; 9(10): 1697-1708, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37666962

RESUMO

Abscisic acid (ABA) is a phytohormone essential to the regulation of numerous aspects of plant growth and development. The cellular level of ABA is critical to its signalling and is determined by its rate of biosynthesis, catabolism and the rates of ABA transport. ABCG25 in Arabidopsis thaliana has been identified to be an ABA exporter and play roles in regulating stomatal closure and seed germination. However, its ABA transport mechanism remains unknown. Here we report the structures of ABCG25 under different states using cryo-electron microscopy single particle analysis: the apo state and ABA-bound state of the wild-type ABCG25 and the ATP-bound state of the ATPase catalytic mutant. ABCG25 forms a homodimer. ABA binds to a cone-shaped, cytosolic-facing cavity formed in the middle of the transmembrane domains. Key residues in ABA binding are identified and verified by a cell-based ABA transport assay. ATP binding leads to closing of the nucleotide-binding domains of opposing monomers and conformational transitions of the transmembrane domains. Together, these results provide insights into the substrate recognition and transport mechanisms of ABCG25 in Arabidopsis, and facilitate our understanding of the ABA transport and signalling pathway in plants.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Trifosfato de Adenosina/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Microscopia Crioeletrônica , Regulação da Expressão Gênica de Plantas , Mutação , Transportadores de Cassetes de Ligação de ATP/metabolismo
11.
Medicine (Baltimore) ; 102(39): e35221, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773838

RESUMO

BACKGROUND: Recent studies have shown substantial progress in understanding the association between epigenetics and autoimmune diseases. However, there is a lack of comprehensive bibliometric analysis in this research area. This article aims to present the current status and hot topics of epigenetic research in autoimmune diseases (ADs) from a bibliometric perspective, as well as explore the frontier hotspots and trends in epigenetic studies related to ADs. METHODS: This study collected 1870 epigenetic records related to autoimmune diseases from the web of science core collection database, spanning from 2012 to 2022. Analysis of regions, institutions, journals, authors, and keywords was conducted using CiteSpace, VOSviewer, and the R package "bibliometrix" to predict the latest trends in epigenetic research relevant to autoimmune diseases. RESULTS: The number of epigenetic publications related to autoimmune diseases has been increasing annually. The United States has played a major role in this field, contributing over 45.9% of publications and leading in terms of publication volume and citation counts. Central South University emerged as the most active institution, contributing the highest number of publications. Frontiers in Immunology is the most popular journal in this field, publishing the most articles, while the Journal of Autoimmunity is the most co-cited journal. Lu QJ is the most prolific author, and Zhao M is the most frequently co-cited author. "Immunology" serves as a broad representative of epigenetic research in ADs. Hot topics in the field of epigenetic modifications associated with autoimmune diseases include "regulatory T cells (Treg)," "rheumatoid arthritis," "epigenetic regulation," "cAMPresponsive element modulator alpha," "cell-specific enhancer," "genetic susceptibility," and "systemic lupus erythematosus." Furthermore, the study discusses the frontiers and existing issues of epigenetic modifications in the development of autoimmune diseases. CONCLUSIONS: This study provides a comprehensive overview of the knowledge structure and developmental trends in epigenetic research related to autoimmune diseases over the past 11 years.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Humanos , Epigênese Genética , Doenças Autoimunes/genética , Artrite Reumatoide/genética , Bibliometria
12.
J Voice ; 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37541926

RESUMO

OBJECTIVE: This study aimed to investigate the effects of different types of masks on acoustic, aerodynamic, and formant parameters in healthy people. METHODS: Our study involved 30 healthy participants, 15 of each gender, aged 20-40 years. The tests were conducted under four conditions: without a mask, after wearing a surgical mask, after wearing a head-mounted N95 mask, and after wearing an ear-mounted N95 mask. Voice recording was done with the mask on. The acoustic parameters include mean fundamental frequency (F0), mean intensity, percentage of jitter (local), percentage of shimmer (local), mean noise to harmonic ratio (NHR), aerodynamic parameter, maximum phonation time (MPT), and formant parameters (/a/, /i/, /u/ three vowels F1, F2). RESULTS: The main effect of mask type was significant in MPT, mean F0, mean HNR, /a/F1, /a/F2, /i/F2. However, the effect sizes and power in /a/F2, /i/F2 were low. MPT, mean F0 and mean HNR significantly increased and /a/F1 significantly decreased after wearing the head-mounted n95 mask. The mean F0 and mean HNR increased significantly after wearing the ear-mounted n95 mask. No significant changes were observed in parameters after wearing the surgical mask in this study. When the statistics are performed separately for males and females, the results obtained are similar to those previously obtained for unspecified males and females. CONCLUSION: After wearing the surgical mask, this study found insignificant changes in mean F0, jitter (local), shimmer (local), mean NHR, mean intensity, MPT, and the vowels F1 and F2. This may be due to the looser design of the surgical mask and the relatively small attenuation of sound. N95 masks have a greater effect on vocalization than surgical masks and may cause changes in F0 and HNR after wearing an N95 mask. In the present study, no significant changes in jitter and shimmer were observed after wearing the mask. In addition, there was a significant reduction in /a/F1 after wearing the N95 headgear mask may owing to its high restriction of jaw mobility. In future studies, the change in jaw movement amplitude after wearing the mouthpiece can be added to investigate.

13.
Phytomedicine ; 118: 154967, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37490802

RESUMO

BACKGROUND: Guizhi Shaoyao Zhimu decoction, a traditional Chinese medicine formula used empirically for the treatment of rheumatoid arthritis (RA), has been shown to alleviate bone destruction in rats with collagen-induced arthritis (CIA). PURPOSE: The aim of this study is to characterize the effects of Guizhi Shaoyao Zhimu granules (GSZGs) on bone destruction in RA and the underlying mechanism. STUDY DESIGN: A CIA arthritis model using DBA/1 mice. The animals were divided into a normal group; CIA model group; low, medium, and high-dose GSZG groups (3, 6, and 9 g/kg/day); and a methotrexate group (1.14 mg/kg/w). In vitro, a cytokine induced osteoclastogenesis model was established. METHODS: After 28 days of treatment, the paw volume was measured, bone destruction was examined by micro-CT, and the generation of osteoclasts in bone tissue was evaluated via tartrate-resistant acid phosphatase (TRAP) staining. Furthermore, the inhibitory effect and underlying mechanism of action of GSZG on RANKL-induced osteoclastogenesis were investigated in vitro. RESULTS: The in vivo analyses demonstrated that the paw volume and degree of bone erosion of mice in the medium- and high-dose GSZG groups were significantly decreased compared to the CIA model group. In addition, GSZG treatment suppressed the excessive generation of osteoclasts in the bone tissue of CIA mice. In vitro, GSZG inhibited RANKL-induced osteoclastogenesis and osteoclast-mediated bone resorption. Specifically, it only inhibited the generation of osteoclast precursors (OCPs); it had no significant effect on the fusion of OCPs or maturation of osteoclasts. Finally, we showed that the inhibitory effect of GSZG on osteoclastogenesis was related to the promotion of PTEN-induced kinase protein 1 (PINK1)/Parkin pathway-mediated mitophagy of osteoclast precursors, which was verified using a PINK1 knockdown small interfering RNA in OCPs. CONCLUSION: These findings indicate that GSZG is a candidate for the treatment of bone destruction in RA and provide a more detailed elucidation of the mechanism of GSZG anti-RA bone erosion, i.e., inhibition of the ROS/NF-κB axis through the PINK1/Parkin-mediated mitochondrial autophagic pathway to inhibit osteoclast precursor production, compared to the published literature.


Assuntos
Artrite Experimental , Artrite Reumatoide , Reabsorção Óssea , Camundongos , Ratos , Animais , Osteoclastos/metabolismo , Osteogênese , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Mitofagia , Camundongos Endogâmicos DBA , Artrite Reumatoide/tratamento farmacológico , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Proteínas Quinases/metabolismo , Ligante RANK/farmacologia , Ligante RANK/metabolismo
14.
Inflammopharmacology ; 31(4): 1629-1645, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37150762

RESUMO

Quercetin, a typical flavonoid derived from a common natural plant, has multiple biological activities. Previous research in animal models has demonstrated the effectiveness of quercetin in treating rheumatoid arthritis (RA). The pharmacological effects and probable mechanisms of quercetin were evaluated in this study. Three databases, PubMed, Web of Science, and Embase, were searched for relevant studies from the creation of the databases to November 2022. Methodological quality was assessed using the SYRCLE risk of bias tool. STATA 15.1 was used to perform the statistical analysis. This research included 17 studies involving 251 animals. The results indicated that quercetin was able to reduce arthritis scores, paw swelling, histopathological scores, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), C-reactive protein (CRP), malondialdehyde (MDA), reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), nuclear factor kappa B (NF-kB) and increase interleukin-10 (IL-10), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and heme oxygenase-1 (HO-1). These may be related to quercetin's potential anti-inflammatory, anti-oxidative stress, and osteoprotective properties. However, more high-quality animal studies are needed to assess the effect of quercetin on RA. Additionally, the safety of quercetin requires further confirmation. Given the importance of the active ingredient, dose selection and the improvement of quercetin's bioavailability remain to be explored.


Assuntos
Artrite Reumatoide , Quercetina , Animais , Quercetina/farmacologia , Quercetina/uso terapêutico , Estresse Oxidativo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Glutationa/metabolismo , NF-kappa B/metabolismo
15.
Plant Commun ; 4(6): 100632, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37254481

RESUMO

The phytohormone auxin plays central roles in many growth and developmental processes in plants. Development of chemical tools targeting the auxin pathway is useful for both plant biology and agriculture. Here we reveal that naproxen, a synthetic compound with anti-inflammatory activity in humans, acts as an auxin transport inhibitor targeting PIN-FORMED (PIN) transporters in plants. Physiological experiments indicate that exogenous naproxen treatment affects pleiotropic auxin-regulated developmental processes. Additional cellular and biochemical evidence indicates that naproxen suppresses auxin transport, specifically PIN-mediated auxin efflux. Moreover, biochemical and structural analyses confirm that naproxen binds directly to PIN1 protein via the same binding cavity as the indole-3-acetic acid substrate. Thus, by combining cellular, biochemical, and structural approaches, this study clearly establishes that naproxen is a PIN inhibitor and elucidates the underlying mechanisms. Further use of this compound may advance our understanding of the molecular mechanisms of PIN-mediated auxin transport and expand our toolkit in auxin biology and agriculture.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Humanos , Arabidopsis/metabolismo , Naproxeno/farmacologia , Naproxeno/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Ácidos Indolacéticos/metabolismo , Plantas/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/metabolismo
16.
Cell Discov ; 9(1): 36, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37015924

RESUMO

The transient receptor potential channel subfamily A member 1 (TRPA1) ion channel is an evolutionary conserved polymodal sensor responding to noxious temperature or chemical stimuli. Notably, the thermosensitivity of TRPA1 varies among different species or even different isoforms in the same species. However, the underlying molecular basis of its thermo-gating remains largely unknown. Here, we determine the structures of a heat-sensitive isoform of TRPA1 in Drosophila melanogaster in two distinct conformations with cryo-samples prepared at 8 °C. Large conformational changes are observed in the ankyrin repeat domain (ARD) and the coiled-coil domain between the two states. Remarkably, all 17 ankyrin repeats are mapped in the newly resolved conformation, forming a propeller-like architecture. Two intersubunit interfaces are identified in the amino (N)-terminal domain, and play vital roles during both heat and chemical activation as shown by electrophysiological analysis. With cryo-samples prepared at 35 °C, only one conformation is resolved, suggesting possible state transitions during heat responses. These findings provide a basis for further understanding how the ARD regulates channel functions, and insights into the gating mechanism of TRPA1.

17.
Small ; 19(34): e2301625, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37093209

RESUMO

Microorganisms display nonequilibrium predator-prey behaviors, such as chasing-escaping and schooling via chemotactic interactions. Even though artificial systems have revealed such biomimetic behaviors, switching between them by control over chemotactic interactions is rare. Here, a spindle-like iron-based metal-organic framework (MOF) colloidal motor which self-propels in glucose and H2 O2 , triggered by UV light is reported. These motors display intrinsic UV light-triggered fuel-dependent chemotactic interactions, which are used to tailor the collective dynamics of active-passive colloidal mixtures. In particular, the mixtures of active MOF motors with passive colloids exhibit distinctive "chasing-escaping" or "schooling" behaviors, depending on glucose or hydrogen peroxide being used as the fuel. The transition in the collective behaviors is attributed to an alteration in the sign of ionic diffusiophoretic interactions, resulting from a change in the ionic clouds produced. This study offers a new strategy on tuning the communication between active and passive colloids, which holds substantial potentials for fundamental research in active matter and practical applications in cargo delivery, chemical sensing, and particle segregation.

18.
Cancer Med ; 12(9): 10536-10552, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37062057

RESUMO

OBJECTIVE: This study aims to evaluate the risk stratification among elderly Nasopharyngeal carcinoma (NPC) patients (≥60 years old) and select the beneficiaries from concurrent chemotherapy (CCRT) combined with induction chemotherapy (IC). MATERIALS AND METHODS: A total of 909 elderly non-metastatic NPC patients treated with cisplatin-based CCRT or IC + CCRT between January 2007 and December 2016 were included. Prognostic nomograms were generated according to clinical characteristics and serum biomarkers. The survival outcomes of patients treated with CCRT versus IC + CCRT were compared in three well-matched risk groups (high, medium, and low risk) after PSM analysis. Benefit of IC in people older or younger than 70 years and effect of different IC regimens and cycles on prognosis were analyzed. RESULTS: Nomograms of overall survival (OS) (C-index: 0.64, 95% CI, 0.61-0.89) and disease special survival (DSS) (C-index: 0.65, 95% CI, 0.62-0.71) showed good prognostic accuracy. The nomogram for DSS included variables of age, gender, ACE, EBV DNA, N stage, and T stage. OS included variables of age, smoking history, ACE, ALB, EBV DNA, N stage, and T stage. The corresponding 5-year OS rates of high, medium and low risk groups were 87.4%, 82.2%, and 60.9%, respectively (p < 0.001), while the 5-year DSS rates were 92.2%, 84.3%, and 69.0%, respectively (p < 0.001). In the high risk group, IC + CCRT led to significantly higher 5-year OS and DSS rate compared with CCRT (5-year OS rate, 73.5% versus 51.8%, p = 0.006; 5-year DSS rate, 81.4% versus 61.3%, p = 0.002). While in the medium and low risk groups, OS and DSS were not significantly different (OS: p = 0.259, 0.186; DSS: p = 0.29, 0.094). Subgroup analysis showed in the high risk group, only people younger than 70 years old could benefit from IC. TPF and IC cycles of three could lead to the best survival results. CONCLUSION: Compared with CCRT, OS, and DSS among high risk elderly patients were significantly improved by the addition of IC in patients younger than 70 years old. TPF and three IC cycles were recommended.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Idoso , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/radioterapia , Quimioterapia de Indução/efeitos adversos , Quimiorradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medição de Risco
20.
Small ; 19(5): e2204260, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36424173

RESUMO

Active tether and transportation of cargoes on cytoskeletal highway enabled by molecular motors is key for accurate delivery of vesicles and organelles in the complex intracellular environment. Here, a hybrid system composed of colloidal motors and self-assembled lipid tubes is designed to mimic the subcellular traffic system in living cells. The colloidal motors, composed of gold-coated hematite, display light-activated self-propulsion tunable by the light intensity and the concentration of hydrogen peroxide fuel. Importantly, the motors show light-switchable binding with lipid cargoes and attachment to the lipid tubes, whereby the latter act as the motor highways. Upon assembly, the colloidal motor/lipid tube system demonstrates directional delivery of lipid vesicles, emulating intracellular transportation. The assembly and function of the hybrid system are rationalized by a cooperative action of light-triggered electrophoretic and hydrodynamic effects, supported by finite element analysis. A synthetic analog of the biological protein motor/cytoskeletal filament system is realized for the manipulation and delivery of different matter at the microscale, which is expected to be a promising platform for various applications in materials science, nanotechnology, microfluidics, and synthetic biology.


Assuntos
Citoesqueleto , Nanotecnologia , Lipídeos
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