RESUMO
Mitochondria, the dynamic organelles responsible for energy production and cellular metabolism, have the metabolic function of extracting energy from nutrients and synthesizing crucial metabolites. Nevertheless, recent research unveils that intercellular mitochondrial transfer by tunneling nanotubes, tumor microtubes, gap junction intercellular communication, extracellular vesicles, endocytosis and cell fusion may regulate mitochondrial function within recipient cells, potentially contributing to disease treatment, such as nonalcoholic steatohepatitis, glioblastoma, ischemic stroke, bladder cancer and neurodegenerative diseases. This review introduces the principal approaches to intercellular mitochondrial transfer and examines its role in various diseases. Furthermore, we provide a comprehensive overview of the inhibitors and activators of intercellular mitochondrial transfer, offering a unique perspective to illustrate the relationship between intercellular mitochondrial transfer and diseases.
Assuntos
Mitocôndrias , Humanos , Mitocôndrias/metabolismo , Animais , Comunicação Celular , Vesículas Extracelulares/metabolismo , Transporte Biológico , Endocitose/fisiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/terapiaRESUMO
The G-protein-coupled bile acid receptor (GPBAR) conveys the cross-membrane signalling of a vast variety of bile acids and is a signalling hub in the liver-bile acid-microbiota-metabolism axis1-3. Here we report the cryo-electron microscopy structures of GPBAR-Gs complexes stabilized by either the high-affinity P3954 or the semisynthesized bile acid derivative INT-7771,3 at 3 Å resolution. These structures revealed a large oval pocket that contains several polar groups positioned to accommodate the amphipathic cholic core of bile acids, a fingerprint of key residues to recognize diverse bile acids in the orthosteric site, a putative second bile acid-binding site with allosteric properties and structural features that contribute to bias properties. Moreover, GPBAR undertakes an atypical mode of activation and G protein coupling that features a different set of key residues connecting the ligand-binding pocket to the Gs-coupling site, and a specific interaction motif that is localized in intracellular loop 3. Overall, our study not only reveals unique structural features of GPBAR that are involved in bile acid recognition and allosteric effects, but also suggests the presence of distinct connecting mechanisms between the ligand-binding pocket and the G-protein-binding site in the G-protein-coupled receptor superfamily.
Assuntos
Ácidos e Sais Biliares/metabolismo , Microscopia Crioeletrônica , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/ultraestrutura , Regulação Alostérica/efeitos dos fármacos , Ácidos e Sais Biliares/química , Sítios de Ligação/efeitos dos fármacos , Ácidos Cólicos/química , Ácidos Cólicos/farmacologia , Subunidades alfa Gs de Proteínas de Ligação ao GTP/química , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/ultraestrutura , Humanos , Ligantes , Modelos Moleculares , Ligação Proteica , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/química , Especificidade por SubstratoRESUMO
As an essential trace element for organisms, zinc participates in various physiological processes, such as RNA transcription, DNA replication, cell proliferation, and cell differentiation. The destruction of zinc homeostasis is associated with various diseases. Zinc homeostasis is controlled by the cooperative action of zinc transporter proteins that are responsible for the influx and efflux of zinc. Zinc transporter proteins are mainly categorized into two families: Zrt/Irt-like protein (SLC39A/ZIP) family and zinc transporter (SLC30A/ZNT) family. ZIP transporters contain 14 members, namely ZIP1-14, which can be further divided into four subfamilies. Currently, ZIP transporters-regulated zinc homeostasis is one of the research hotspots. Cumulative evidence suggests that ZIP transporters-regulated zinc homeostasis may cause physiological dysfunction and contribute to the onset and progression of diverse diseases, such as cancers, neurological diseases, and cardiovascular diseases. In this review, we initially discuss the structure and distribution of ZIP transporters. Furthermore, we comprehensively review the latest research progress of ZIP transporters-regulated zinc homeostasis in diseases, providing a new perspective into new therapeutic targets for treating related diseases.
Assuntos
Doenças Cardiovasculares , Proteínas de Transporte de Cátions , Neoplasias , Doenças do Sistema Nervoso , Zinco , Animais , Humanos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/genética , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cátions/genética , Homeostase/fisiologia , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Zinco/metabolismo , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/metabolismoRESUMO
Laboratory studies have revealed that strigolatone (SL) and karrikin (KAR) signalling mediate responses to abiotic and biotic stresses, and reshape branching architecture that could increase reproductive performance and crop yields. To understand the ecological function of SL and KAR signalling, transgenic lines of wild tobacco Nicotiana attenuata, silenced in SL/KAR biosynthesis/signalling were grown in the glasshouse and in two field plots in the Great Basin Desert in Utah over four field seasons. Of the lines silenced in SL and KAR signalling components (irMAX2, irD14, irKAI2 and irD14 × irKAI2 plants), which exhibited the expected increases in shoot branching, only irMAX2 plants showed a strong leaf-bleaching phenotype when grown in the field. In the field, irMAX2 plants had lower sugar and higher leaf amino acid contents, lower lifetime fitness and were more susceptible to herbivore attack compared to wild-type plants. These irMAX2 phenotypes were not observed in glasshouse-grown plants. Transcriptomic analysis revealed dramatic responses to high-light intensity in irMAX2 leaves in the field: lutein contents decreased, and transcriptional responses to high-intensity light, singlet oxygen and hydrogen peroxide increased. PAR and UV-B manipulations in the field revealed that the irMAX2 bleaching phenotype is reversed by decreasing PAR, but not UV-B fluence. We propose that NaMAX2 functions in high-light adaptation and fitness optimisation by regulating high-light responses independently of its roles in the SL and KAR signalling pathways. The work provides another example of the value of studying the function of genes in the complex environments in which plants evolved, namely nature.
Assuntos
Nicotiana , Folhas de Planta , Nicotiana/metabolismo , Perfilação da Expressão GênicaRESUMO
BACKGROUND: According to the World Health Organisation's Health Report 2019, approximately 17.18 million people die from cardiovascular disease each year, accounting for more than 30% of all global deaths. Therefore, the occurrence of cardiovascular disease is still a global concern. The transcription factor 21 (TCF21) plays an important role in cardiovascular diseases. This article reviews the regulation mechanism of TCF21 expression and activity and focuses on its important role in atherosclerosis in order to contribute to the development of diagnosis and treatment of cardiovascular diseases. SUMMARY: TCF21 is involved in the phenotypic regulation of vascular smooth muscle cells (VSMCs), promotes the proliferation and migration of VSMCs, and participates in the activation of inflammatory sequences. Increased proliferation and migration of VSMCs can lead to neointimal hyperplasia after vascular injury. Abnormal hyperplasia of neointima and inflammation are one of the main features of atherosclerosis. Therefore, targeting TCF21 may become a potential treatment for relieving atherosclerosis. KEY MESSAGES: TCF21 as a member of basic helix-loop-helix transcription factors regulates cell growth and differentiation by modulating gene expression during the development of different organs and plays an important role in cardiovascular development and disease. VSMCs and cells derived from VSMCs constitute the majority of plaques in atherosclerosis. TCF21 plays a key role in regulation of VSMCs' phenotype, thus accelerating atherogenesis in the early stage. However, TCF21 enhances plaque stability in late-stage atherosclerosis. The dual role of TCF21 should be considered in the translational medicine.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Doenças Cardiovasculares , Músculo Liso Vascular , Humanos , Animais , Músculo Liso Vascular/metabolismo , Doenças Cardiovasculares/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Aterosclerose/metabolismo , Miócitos de Músculo Liso/metabolismo , Proliferação de Células , Movimento CelularRESUMO
OBJECTIVES: To evaluate the changes of cardiac morphology and function in fetuses conceived through assisted reproductive technologies (ART) by speckle tracking echocardiography. METHODS: A retrospective study was conducted in 101 spontaneously conceived (SC) fetuses and 99 ART-conceived ones. Fetal echocardiography was performed, fetal cardiac morphology and function were analyzed using two-dimensional speckle tracking software, including global sphericity index (GSI), global longitudinal strain (GLS), fractional area change (FAC) of the left and right ventricles, as well as segmental sphericity index (SI), end-diastolic diameter (ED), and fractional shortening (FS) in 24 segments. RESULTS: Compared to the SC fetuses, the ART-conceived fetuses exhibited decreased GSI (median [interquartile range], 1.22 [1.16-1.27] vs. 1.18 [1.11-1.24], p=0.007), decreased right ventricular GLS (24.9 [21.5-27.6] vs. 23.2 [20.4-26.8], p=0.026), and decreased right ventricular FAC (mean ± standard deviation, 39.7 ± 6.4 vs. 37.2 ± 7.1, p=0.003). Analysis of the 24 segments showed that ART-conceived fetuses had reduced SI in the apical segments of right ventricle and increased ED in several segments of the right ventricle. CONCLUSIONS: Fetuses conceived through ART had a more spherical shape of the global heart and predominantly right-sided cardiac remodeling and systolic function impairment.
Assuntos
Ecocardiografia , Coração Fetal , Humanos , Estudos Retrospectivos , Coração Fetal/diagnóstico por imagem , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Técnicas de Reprodução AssistidaRESUMO
As the most known therapeutic component of bear bile acids, ursodeoxycholic acid (UDCA) is an FDA-approved drug for the treatment of primary biliary cirrhosis (PBC), the dissolution of cholesterol gallstones. UDCA produces many beneficial effects on metabolism and immune responses via its interaction with the membrane G protein-coupled bile acid receptor (GPBAR); however, how UDCA interacts with GPBAR and its selective cellular effects remain elusive. In this study, we delineated the interaction of UDCA with GPBAR and activation mechanism of GPBAR by scattered alanine scanning and molecular docking. Our results indicated that transmembrane helix 2 (TM2), TM3, TM5 and TM6 of GPBAR contribute to the interaction of UDCA in GPBAR binding pocket. Moreover, we predicted that the engagement of the 3-OH of UDCA with phenolic oxygen of Y2406.51 in GPBAR plays a key role in GPBAR activation. Unexpectedly, in addition to the well-known roles of intracellular loop2 (ICL2) residues, we identified that ICL3 residues play an important role in G protein coupling to GPBAR in response to UDCA binding. Our study provides a preliminary molecular mechanism of how GPBAR recognizes UDCA and subsequent activation and G protein interaction, which may facilitate the development of new bile acid derivatives as therapeutics.
Assuntos
Ácidos e Sais Biliares , Ácido Ursodesoxicólico , Alanina , Proteínas de Ligação ao GTP/metabolismo , Simulação de Acoplamento Molecular , Receptores Acoplados a Proteínas G/metabolismo , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
BACKGROUND: Slick, a sodium-activated potassium channel, has been recently identified in somatosensory pathways, but its functional role is poorly understood. The authors of this study hypothesized that Slick is involved in processing sensations of pain and itch. METHODS: Immunostaining, in situ hybridization, Western blot, and real-time quantitative reverse transcription polymerase chain reaction were used to investigate the expression of Slick in dorsal root ganglia and the spinal cord. Mice lacking Slick globally (Slick-/-) or conditionally in neurons of the spinal dorsal horn (Lbx1-Slick-/-) were assessed in behavioral models. RESULTS: The authors found Slick to be enriched in nociceptive Aδ-fibers and in populations of interneurons in the spinal dorsal horn. Slick-/- mice, but not Lbx1-Slick-/- mice, showed enhanced responses to noxious heat in the hot plate and tail-immersion tests. Both Slick-/- and Lbx1-Slick-/- mice demonstrated prolonged paw licking after capsaicin injection (mean ± SD, 45.6 ± 30.1 s [95% CI, 19.8 to 71.4]; and 13.1 ± 16.1 s [95% CI, 1.8 to 28.0]; P = 0.006 [Slick-/- {n = 8} and wild-type {n = 7}, respectively]), which was paralleled by increased phosphorylation of the neuronal activity marker extracellular signal-regulated kinase in the spinal cord. In the spinal dorsal horn, Slick is colocalized with somatostatin receptor 2 (SSTR2), and intrathecal preadministration of the SSTR2 antagonist CYN-154806 prevented increased capsaicin-induced licking in Slick-/- and Lbx1-Slick-/- mice. Moreover, scratching after intrathecal delivery of the somatostatin analog octreotide was considerably reduced in Slick-/- and Lbx1-Slick-/- mice (Slick-/- [n = 8]: 6.1 ± 6.7 bouts [95% CI, 0.6 to 11.7]; wild-type [n =8]: 47.4 ± 51.1 bouts [95% CI, 4.8 to 90.2]; P = 0.039). CONCLUSIONS: Slick expressed in a subset of sensory neurons modulates heat-induced pain, while Slick expressed in spinal cord interneurons inhibits capsaicin-induced pain but facilitates somatostatin-induced itch.
Assuntos
Capsaicina , Células do Corno Posterior , Animais , Capsaicina/efeitos adversos , Capsaicina/metabolismo , Gânglios Espinais/metabolismo , Camundongos , Dor , Células do Corno Posterior/metabolismo , Canais de Potássio , Prurido/induzido quimicamente , Células Receptoras Sensoriais/metabolismo , Canais de Sódio , Somatostatina/efeitos adversos , Somatostatina/metabolismo , Medula Espinal/metabolismoRESUMO
Previous studies suggest that adenosine A1 receptors (A1R) modulate the processing of pain. The aim of this study was to characterize the distribution of A1R in nociceptive tissues and to evaluate whether targeting A1R with the partial agonist capadenoson may reduce neuropathic pain in mice. The cellular distribution of A1R in dorsal root ganglia (DRG) and the spinal cord was analyzed using fluorescent in situ hybridization. In behavioral experiments, neuropathic pain was induced by spared nerve injury or intraperitoneal injection of paclitaxel, and tactile hypersensitivities were determined using a dynamic plantar aesthesiometer. Whole-cell patch-clamp recordings were performed to assess electrophysiological properties of dissociated DRG neurons. We found A1R to be expressed in populations of DRG neurons and dorsal horn neurons involved in the processing of pain. However, administration of capadenoson at established in vivo doses (0.03-1.0 mg/kg) did not alter mechanical hypersensitivity in the spared nerve injury and paclitaxel models of neuropathic pain, whereas the standard analgesic pregabalin significantly inhibited the pain behavior. Moreover, capadenoson failed to affect potassium currents in DRG neurons, in contrast to a full A1R agonist. Despite expression of A1R in nociceptive neurons, our data do not support the hypothesis that pharmacological intervention with partial A1R agonists might be a valuable approach for the treatment of neuropathic pain.
Assuntos
Agonistas do Receptor A1 de Adenosina/uso terapêutico , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Receptor A1 de Adenosina/biossíntese , Agonistas do Receptor A1 de Adenosina/farmacologia , Animais , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Receptor A1 de Adenosina/genética , Resultado do TratamentoRESUMO
The sodium-activated potassium channel Slack (KNa1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (IKNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated IKNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated IKNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.
Assuntos
Trifosfato de Adenosina/análogos & derivados , Cálcio/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Neuralgia/metabolismo , Canais de Potássio Ativados por Sódio/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Células Receptoras Sensoriais/fisiologia , Trifosfato de Adenosina/farmacologia , Animais , Escala de Avaliação Comportamental , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Técnicas de Patch-Clamp , Nervos Periféricos/patologia , Canais de Potássio/metabolismo , Canais de Potássio/fisiologia , Canais de Potássio Ativados por Sódio/genética , Receptores Purinérgicos P2X3/fisiologia , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
The screening and identification of hyperaccumulators is the key to the phytoremediation of soils contaminated by heavy metal (HM). Arbuscular mycorrhizal fungus (AMF) can improve plant growth and tolerance to HM; therefore, AMF-assisted phytoextraction has been regarded as a potential technique for the remediation of HM-polluted soils. A greenhouse pot experiment was conducted to determine whether Sphagneticola calendulacea is a Cd-hyperaccumulator and to investigate the effect of the AMF-Funneliformis mosseae (FM) on plant growth and on the accumulation, subcellular distribution and chemical form of Cd in S. calendulacea grown in soils supplemented with different Cd levels. At 25, 50 and 100 mg Cd kg-1 level, S. calendulacea showed high Cd tolerance, the translocation factor and the bioconcentration factor exceeded 1, and accumulation of more than 100 mg Cd kg-1 was observed in the aboveground parts of the plant, meeting the requirements for a Cd-hyperaccumulator. Moreover, FM colonization significantly increased both biomasses and Cd concentration in S. calendulacea. After FM inoculation, the Cd concentrations and proportions increased in the cell walls, but exhibited no significant change in the organelles of the shoots. Meanwhile, FM symbiosis contributed to the conversion of Cd from highly toxic chemical forms (extracted by 80% ethanol and deionized water) to less toxic chemical forms (extracted by 1 M NaCl, 2% acetic acid, 0.6 M HCl) of Cd in the shoots. Overall, S. calendulacea is a typical Cd-hyperaccumulator, and FM symbiosis relieved the phytotoxicity of Cd and promoted plant growth and Cd accumulation, and thus greatly increasing the efficiency of phytoextraction for Cd-polluted soil. Our study provides a theoretical basis and application guidance for the remediation of Cd-contaminated soil by the symbiont of S. calendulacea with FM.
Assuntos
Asteraceae/metabolismo , Bioacumulação , Cádmio/metabolismo , Glomeromycota/fisiologia , Micorrizas/fisiologia , Poluentes do Solo/metabolismo , Asteraceae/crescimento & desenvolvimento , Asteraceae/microbiologia , Biodegradação AmbientalRESUMO
Astragaloside IV(AS-IV), a saponin purified from Astragalus membranaceus (Fisch.) Bge.var.mongholicus (Bge.) Hsiao, has been widely used in traditional Chinese medicine. However, the underlying mechanisms in treating chronic glomerular nephritis (CGN) have not been fully understood. The aim of the present study was to evaluate the potential mechanism of AS-IV on CGN. CGN rats were administrated with AS-IV at 10 mg·kg-1 ·d-1 (ASL) and 20 mg·kg-1 ·d-1 (ASH). Twenty four hour proteinuria, blood urea nitrogen (BUN), and serum creatinine (SCr) were detected. Hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining were performed to evaluate the kidney lesion. Transmission electron microscope and GFP-RFP-LC3 transfection assay were used to monitor the effect of AS-IV on autophagy. IL-6 and IL-1ß were detected. The expression of CyclinD1, PI3K/AKT/AS160 pathway and autophagy related proteins were detected by Western Blot. The results demonstrated that AS-IV improved kidney function, ameliorated kidney lesion, and diminished inflammatory in CGN rats. Further, both in vivo and vitro study demonstrated that AS-IV inhibited the proliferation of mesangial cells. AS-IV further displayed a remarkable effect on inhibiting the activation of PI3K/AKT/AS160 pathway and improved the activation of autophagy in vivo and vitro. These results suggested that AS-IV is a potential therapeutic agent for CGN and merits further investigation.
Assuntos
Autofagia/efeitos dos fármacos , Glomerulonefrite/prevenção & controle , Insuficiência Renal Crônica/prevenção & controle , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Astragalus propinquus/química , Células Cultivadas , Citoproteção/efeitos dos fármacos , Proteínas Ativadoras de GTPase/metabolismo , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
A greenhouse pot experiment was conducted to assess the effects of biochar (BC) and arbuscular mycorrhizal fungus (AMF)-Funneliformis mosseae (Fm), Glomus versiforme (Gv) and Rhizophagus intraradices (Ri) on the plant growth and Cd/Pb accumulation by corn grown in the soils artificially contaminated with 5 mg Cd and 300 mg Pb kg-1 soil. The single AMF inoculation and combined usage of AMF and BC evidently improved the P contents of maize. Furthermore, the combined use of AMF and BC produced pronounced positive effect on corn growth, and the shoot biomass in Gv + BC group was 9.85-fold higher than that of the control. Meanwhile, the single BC addition and combined utilization of AMF and BC significantly reduced Cd and Pb concentrations in maize, and the greater reduces were found in the combined utilization, and the lowest Cd concentration of shoot was appeared in Gv + BC group. The single BC addition and combined application of AMF and BC significantly increased soil pH, and reduced soil diethylenetriaminepentaacetic acid (DTPA)-extractable Cd/Pb. This study demonstrated a synergistic effect between AMF (Gv, Fm, Ri) and BC on improving maize growth and decreasing Cd/Pb accumulation in maize, and the combined use of Gv and BC brought the most pronounced effect, which could provide a feasible strategy for safe production of maize from Cd/Pb-polluted soils.
Assuntos
Micorrizas , Poluentes do Solo/análise , Biodegradação Ambiental , Cádmio/análise , Carvão Vegetal , Chumbo , Raízes de Plantas/química , Solo , Zea maysRESUMO
Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a severe dose- and therapy-limiting side effect of widely used cytostatics that is particularly difficult to treat. Here, we report increased expression of the cytochrome-P450-epoxygenase CYP2J6 and increased concentrations of its linoleic acid metabolite 9,10-EpOME (9,10-epoxy-12Z-octadecenoic acid) in dorsal root ganglia (DRGs) of paclitaxel-treated mice as a model of CIPNP. The lipid sensitizes TRPV1 ion channels in primary sensory neurons and causes increased frequency of spontaneous excitatory postsynaptic currents in spinal cord nociceptive neurons, increased CGRP release from sciatic nerves and DRGs, and a reduction in mechanical and thermal pain hypersensitivity. In a drug repurposing screen targeting CYP2J2, the human ortholog of murine CYP2J6, we identified telmisartan, a widely used angiotensin II receptor antagonist, as a potent inhibitor. In a translational approach, administration of telmisartan reduces EpOME concentrations in DRGs and in plasma and reverses mechanical hypersensitivity in paclitaxel-treated mice. We therefore suggest inhibition of CYP2J isoforms with telmisartan as a treatment option for paclitaxel-induced neuropathic pain.
Assuntos
Benzimidazóis/farmacologia , Benzoatos/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Neuralgia/prevenção & controle , Paclitaxel/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/toxicidade , Citocromo P-450 CYP2J2 , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Ácidos Linoleicos/sangue , Ácidos Linoleicos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Terapia de Alvo Molecular/métodos , Neuralgia/induzido quimicamente , Paclitaxel/toxicidade , Limiar da Dor/efeitos dos fármacos , TelmisartanRESUMO
Arbuscular mycorrhizal fungus (AMF) can relieve Cd phytotoxicity and improve plant growth, but the mechanisms involved in this process have still been not completely known. In the present work, a pot experiment was conducted to examine productions of glutathione (GSH) and phytochelatins (PCs), and absorption, chemical forms and subcellular distribution of Cd in maize (Zea mays) inoculated with or without AMF (Rhizophagus intraradices (Ri) and Glomus versiforme (Gv)) in Cd-amended soils (0, 1 and 5â¯mgâ¯Cdâ¯kg-1 soil). In general, both Ri and Gv inoculation dramatically enhanced biomass production and reduced Cd concentrations in shoots and roots of maize when compared to the non-mycorrhizal treatment. Moreover, both Ri and Gv symbiosis obviously increased contents of GSH and PCs, both in shoots and roots. Subcellular distribution of Cd in maize indicated that most of Cd (more than 90%) was accumulated in cell wall and soluble fraction. In addition, Cd proportions in soluble fractions in shoots of maize inoculated with Gv or Ri were considerably increased, but reduced in cell wall fractions compared to non-mycorrhizal maize, indicating that mycorrhizal symbiosis promoted Cd transfer to vacuoles. Furthermore, proportions of Cd in inorganic and water-soluble forms were declined, but elevated in pectates and proteins-integrated forms in mycorrhizal maize, which suggested that Gv and Ri could convert Cd into inactive forms. These observations could provide a further understanding of potential Cd detoxification mechanism in maize inoculated with AMF.
Assuntos
Cádmio/metabolismo , Cádmio/toxicidade , Glomeromycota , Micorrizas/metabolismo , Zea mays/metabolismo , Biomassa , Cádmio/análise , Parede Celular/metabolismo , Glutationa/metabolismo , Fitoquelatinas/metabolismo , Desenvolvimento Vegetal , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Simbiose , Vacúolos/metabolismo , Zea mays/crescimento & desenvolvimentoRESUMO
Little attention has been paid to the combined use of arbuscular mycorrhizal fungus (AMF) and steel slag (SS) for ameliorating heavy metal polluted soils. A greenhouse pot experiment was conducted to study the effects of SS and AMF-Funneliformis mosseae (Fm), Glomus versiforme (Gv) and Rhizophagus intraradices (Ri) on plant growth and Cd, Pb uptake by maize grown in soils added with 5 mg Cd kg-1 and 300 mg Pb kg-1 soil. The combined usage of AMF and SS (AMF + SS) promoted maize growth, and Gv + SS had the most obvious effect. Meanwhile, single SS addition and AMF + SS decreased Cd, Pb concentrations in maize, and the greater reductions were found in combined utilization, and the lowest Cd, Pb concentrations of maize appeared in Gv + SS. Single SS amendment and AMF + SS enhanced soil pH and decreased soil diethylenetriaminepentaacetic acid (DTPA)-extractable Cd, Pb concentrations. Furthermore, alone and combined usage of AMF and SS increased contents of soil total glomalin. Our research indicated a synergistic effect between AMF and SS on enhancing plant growth and reducing Cd, Pb accumulation in maize, and Gv + SS exerted the most pronounced effect. This work suggests that AMF inoculation in combination with SS addition may be a potential method for not only phytostabilization of Pb-Cd-contaminated soil but maize safety production.
Assuntos
Micorrizas , Poluentes do Solo/análise , Biodegradação Ambiental , Cádmio/análise , Chumbo , Raízes de Plantas , Aço , Zea maysRESUMO
Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain.
Assuntos
Hiperalgesia/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neuralgia/metabolismo , Canais de Potássio/metabolismo , Células Receptoras Sensoriais/metabolismo , Animais , Temperatura Alta , Hiperalgesia/genética , Hiperalgesia/fisiopatologia , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Neuralgia/fisiopatologia , Medição da Dor , Limiar da Dor/fisiologia , Física , Canais de Potássio/genética , Canais de Potássio Ativados por SódioRESUMO
OBJECTIVE: This study is aimed at examining the effects of Maxing Shigan Tang (MST) treatment on H1N1-associated acute lung injury (ALI) and exploring the possible mechanism. MATERIAL AND METHODS: Mice were randomly divided into a control group, model group, peroxisomal proliferator activator receptor γ (PPARγ) inhibition group (PPARγ-), PPARγ activation group (PPARγ+), and MST group. Influenza A (H1N1) virus of the Fort Monmouth 1 (FM1) strain was used to induce an ALI mice model. Hematoxylin and eosin staining was performed to investigate the effect of MST treatment on H1N1-associated ALI. Cell apoptosis of lung tissues of each group were conducted through transferase-mediated dUTP nick end-labeling methods. Moreover, the expression level of caspase 3, activity of caspase 3, and serum level of tumor necrosis factor (TNF)-α of each group were also analyzed. Finally, quantitative real-time polymerase chain reaction and Western blotting analysis were carried out to detect angiopoietin-like 4 (ANGPTL4) expression level. RESULTS: We found that mice infected with the FM1 strain of H1N1 influenza A virus developed severe ALI, and MST could improve H1N1-induced ALI. Moreover, MST decreased lung cell apoptosis and reduced the serum content of TNF-α. In addition, MST significantly induced the ANGPTL4 expression in H1N1-induced ALI. CONCLUSION: MST improves H1N1-associated ALI maybe through targeting ANGPTL4 in mice.
RESUMO
In the present study, the biological effect of TiO2 nanoparticles on cyanobacteria cells was studied using Microcystis aeruginosa (M. aeruginosa) as a model. Nano-TiO2 as a photo-catalysts agent used for water treatment may pose a risk to ecosystems, especially for the water organisms such as cyanobacteria. Scanning electron microscope (SEM) images provided that with the increasing of photocatalytic time, slime layer on the cell surface was damaged and sunk. Attenuated total reflectance fourier transform infrared (ATR-FTIR) spectroscopy revealed that the vibration peaks of C-C, C-H, C=O, P=O weakened within 12 h. According to the dynamic analysis of the infrared peaks, the damage on the cell groups under nano-TiO2 photocatalysis with different time periods was analyzed. The concentrations of K(+), Ca(2+), Mg(2+) released from the cells were measured, which indicated that nano-TiO2 photocatalysis have changed the cell membrane permeability and fluidity of M. aeruginosa.
Assuntos
Microcystis/efeitos dos fármacos , Nanopartículas/toxicidade , Titânio/toxicidade , Raios Ultravioleta , Purificação da Água/métodos , Cálcio/metabolismo , Catálise , Magnésio/metabolismo , Microscopia Eletrônica de Varredura , Potássio/metabolismo , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
In order to determine the suitable harvest time of Dendrobium officinale from different regions in Yunnan province, the drying rate, mannose and glucose peak area ratio, extract, contents of polysaccharide and mannose of D. officinale samples collected from six producing areas in Ynnnan province were determined. The results indicate that drying rate and the contents of polysaccharide and mannose arrived the peak from January to April, extract reached a higher content from September to December, and mannose and glucose peak area ratio from October to February of the coming met the requirment of the Chinese Pharmacopoeia. Hence, the suitable harvesting time of D. officinale in Yunnan province is from December to February of the coming year,according to the experimental results and the request of the Chinese Pharmacopoeia.