Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 711
Filtrar
1.
Nat Commun ; 15(1): 5705, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977710

RESUMEN

In nature, coenzyme-independent oxidases have evolved in selective catalysis using isolated substrate-binding pockets. Single-atom nanozymes (SAzymes), an emerging type of non-protein artificial enzymes, are promising to simulate enzyme active centers, but owing to the lack of recognition sites, realizing substrate specificity is a formidable task. Here we report a metal-ligand dual-site SAzyme (Ni-DAB) that exhibited selectivity in uric acid (UA) oxidation. Ni-DAB mimics the dual-site catalytic mechanism of urate oxidase, in which the Ni metal center and the C atom in the ligand serve as the specific UA and O2 binding sites, respectively, characterized by synchrotron soft X-ray absorption spectroscopy, in situ near ambient pressure X-ray photoelectron spectroscopy, and isotope labeling. The theoretical calculations reveal the high catalytic specificity is derived from not only the delicate interaction between UA and the Ni center but also the complementary oxygen reduction at the beta C site in the ligand. As a potential application, a Ni-DAB-based biofuel cell using human urine is constructed. This work unlocks an approach of enzyme-like isolated dual sites in boosting the selectivity of non-protein artificial enzymes.


Asunto(s)
Oxidación-Reducción , Urato Oxidasa , Ácido Úrico , Especificidad por Sustrato , Urato Oxidasa/química , Urato Oxidasa/metabolismo , Ácido Úrico/química , Ácido Úrico/metabolismo , Ácido Úrico/orina , Ligandos , Humanos , Níquel/química , Níquel/metabolismo , Sitios de Unión , Dominio Catalítico , Catálisis , Modelos Moleculares , Espectroscopía de Absorción de Rayos X
2.
J Hazard Mater ; 476: 135045, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38944990

RESUMEN

Isoprocarb (IPC), a representative monocyclic carbamate insecticide, poses risks of environmental contamination and harm to non-target organisms. However, its degradation mechanism has not been reported. In this study, a newly IPC-degrading strain D-6 was isolated from the genus Rhodococcus, and its degradation characteristics and pathway of IPC were analyzed. A novel hydrolase IpcH, responsible for hydrolyzing IPC to 2-isopropylphenol (IPP), was identified. IpcH exhibited low similarity (< 27 %) with other reported hydrolases, including previously characterized carbamate insecticides hydrolases, indicating its novelty. The Km and kcat values of IpcH towards IPC were 69.99 ± 8.33 µM and 95.96 ± 4.02 s-1, respectively. Also, IpcH exhibited catalytic activity towards various types of carbamate insecticides, including monocyclic carbamates (IPC, fenobucarb and propoxur), bicyclic carbamates (carbaryl and carbofuran), and linear carbamates (oxamyl and aldicarb). The molecular docking and site-directed mutagenesis revealed that His254, His256, His329 and His376 were essential for IpcH activity. Strain D-6 can effectively reduce the toxicity of IPC and IPP towards sensitive organisms through its degradation ability. This study presents the initial report on IPC degradation pathway and molecular mechanism of IPC degradation, and provides a good potential strain for bioremediating IPC and IPP-contaminated environments.

3.
Drug Des Devel Ther ; 18: 2227-2248, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38882046

RESUMEN

Purpose: The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics. Methods: First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters. Results: BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment. Conclusion: BDD can effectively improve anxiety-like behaviors by regulating the gut-brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters.


Asunto(s)
Ansiolíticos , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Metabolómica , Ratas Sprague-Dawley , Animales , Ratas , Ansiolíticos/farmacología , Medicamentos Herbarios Chinos/farmacología , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Ansiedad/tratamiento farmacológico , Ansiedad/metabolismo , Restricción Física , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo
4.
Front Neurol ; 15: 1393022, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846044

RESUMEN

Purpose: The prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field. Methods: Relevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package "Bibliometrix" for bibliometric analysis. Results: A total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. "chronic pain," "neuropathic pain," "psychological pain" are the keywords in the research. Conclusion: This is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future.

5.
Front Endocrinol (Lausanne) ; 15: 1410370, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38872963

RESUMEN

Background: The involvement of ATP and cAMP in sperm function has been extensively documented, but the understanding of the role of adenosine and adenosine receptors remains incomplete. This study aimed to examine the presence of adenosine A2A receptor (A2AR) and study the functional role of A2AR in human sperm. Methods: The presence and localization of A2AR in human sperm were examined by western blotting and immunofluorescence assays. The functional role of A2AR in sperm was assessed by incubating human sperm with an A2AR agonist (regadenoson) and an A2AR antagonist (SCH58261). The sperm level of A2AR was examined by western blotting in normozoospermic and asthenozoospermic men to evaluate the association of A2AR with sperm motility and in vitro fertilization (IVF) outcomes. Results: A2AR with a molecular weight of 43 kDa was detected in the tail of human sperm. SCH58261 decreased the motility, penetration ability, intracellular Ca2+ concentration, and CatSper current of human sperm. Although regadenoson did not affect these sperm parameters, it alleviated the adverse effects of SCH58261 on these parameters. In addition, the mean level of A2AR in sperm from asthenozoospermic men was lower than that in sperm from normozoospermic men. The sperm level of A2AR was positively correlated with progressive motility. Furthermore, the fertilization rate during IVF was lower in men with decreased sperm level of A2AR than in men with normal sperm level of A2AR. Conclusions: These results indicate that A2AR is important for human sperm motility and is associated with IVF outcome.


Asunto(s)
Fertilización In Vitro , Receptor de Adenosina A2A , Motilidad Espermática , Espermatozoides , Humanos , Masculino , Motilidad Espermática/efectos de los fármacos , Receptor de Adenosina A2A/metabolismo , Espermatozoides/metabolismo , Espermatozoides/efectos de los fármacos , Fertilización In Vitro/métodos , Adulto , Astenozoospermia/metabolismo , Femenino , Pirazoles/farmacología , Agonistas del Receptor de Adenosina A2/farmacología , Antagonistas del Receptor de Adenosina A2/farmacología , Pirimidinas/farmacología , Triazoles/farmacología
6.
World J Clin Cases ; 12(17): 2946-2950, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38898826

RESUMEN

Hypoparathyroidism is one of the main complications after total thyroidectomy, severely affecting patients' quality of life. How to effectively protect parathyroid function after surgery and reduce the incidence of hypoparathyroidism has always been a key research area in thyroid surgery. Therefore, precise localization of parathyroid glands during surgery, effective imaging, and accurate surgical resection have become hot topics of concern for thyroid surgeons. In response to this clinical phenomenon, this study compared several different imaging methods for parathyroid surgery, including nanocarbon, indocyanine green, near-infrared imaging techniques, and technetium-99m methoxyisobutylisonitrile combined with gamma probe imaging technology. The advantages and disadvantages of each method were analyzed, providing scientific recommendations for future parathyroid imaging. In recent years, some related basic and clinical research has also been conducted in thyroid surgery. This article reviewed relevant literature and provided an overview of the practical application progress of various imaging techniques in parathyroid surgery.

7.
J Hazard Mater ; 476: 134968, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901263

RESUMEN

The widely used phenylurea herbicide isoproturon (IPU) and its residues can inhibit the growth of subsequently planted crops. However, reports on bioremediation of IPU-contaminated soil are scarce. In this study, Sphingobium sp. strain YBL2-gfp (a derivative of the IPU-degrading Sphingobium sp. strain YBL2 isolated by our lab) was constructed to bioremediate IPU-contaminated soil. In pot experiments, strain YBL2-gfp colonized the roots of wheat and eliminated IPU residues in the soil within 21 d, effectively alleviating its toxicity and restoring wheat growth. IPU treatment reduced the richness and diversity of soil bacteria, while inoculation YBL2-gfp mainly affected richness with less impact on diversity. The high concentrations of IPU and inoculation of YBL2-gfp alone reduced the soil microbial community connections, while bioaugmentation treatment enhanced the soil microbial community connections. Additionally, strain YBL2-gfp stimulated the metabolic capacity of the indigenous microbes, promoting the degradation of IPU and reducing the negative impact of high concentrations of IPU on microbial community. Taken together, this study offers relatively comprehensive insights into the practical application of bioaugmentation, demonstrating that strain YBL2 has the potential to remediate IPU-contaminated soils.

8.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2489-2500, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38812153

RESUMEN

This study aims to reveal the molecular mechanism of Chaijin Jieyu Anshen Tablets(CJJYAS) in regulating the abnormal anterior cingulate cortex(ACC)-ventral hippocampus(vHPC) glutaminergic neural circuit to alleviate synaptic remodeling of ventral hippocampal neurons in depressed rats. Firstly, the study used chemogenetics to localize glutaminergic adeno-associated virus(AAV) into the ACC brain region of rats. The model of depressed rats was established by chronic unpredictable mild stress(CUMS) combined with independent feeding. The rats were randomly divided into control group, model group, AAV empty group, AAV group, AAV+ glucocorticoid receptors(GR) blocker group, AAV+chemokine receptor 1(CX3CR1) blocker group, and AAV+CJJYAS group. Depressive-like behaviors of rats were evaluated by open-field, forced-swimming, and Morris water maze tests, combined with an animal behavior analysis system. The morphological and structural changes of ACC and vHPC neurons in rats were observed by hematoxylin-eosin(HE) staining. Immunofluorescence and nuclear phosphoprotein(c-Fos) were used to detect glutaminergic neural circuit activation of ACC-vHPC in rats. The changes in dendrites, synaptic spines, and synaptic submicrostructure of vHPC neurons were observed by Golgi staining and transmission electron microscopy, respectively. The expressions of synaptic remodeling-related proteins N-methyl-D-asprtate receptor 2A(GRIN2A), N-methyl-D-asprtate receptor 2B(GRIN2B), Ca~(2+)/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ), mitogen-activated protein kinase-activated protein kinase 2(MK2), and a ubiquitous actin-binding protein(cofilin) in vHPC glutaminergic neurons of rats were detected by immunofluorescence and Western blot, respectively. The results indicated that the activated glutaminergic AAV aggravated the depressive-like behaviors phenotype of rats in the model group and deteriorated the damage of morphology and structure of ACC and vHPC neurons and synaptic ultrastructure. However, both GR and CX3CR1 bloc-kers could reverse the abnormal changes to varying degrees, suggesting that the abnormal activation of ACC-vHPC glutaminergic neural circuit mediated by GR/CX3CR1 signals in gliocytes in the ACC brain region may be closely related to the occurrence and development of depression. Interestingly, CJJYAS significantly inhibited the activation of the ACC-vHPC glutaminergic neural circuit induced by AAV and the elevated Glu level. Furthermore, CJJYAS could also effectively reverse the aggravation of depressive-like behaviors and synaptic remodeling of vHPC neurons of rats in the model group induced by the activated AAV. Additionally, the findings suggested that the molecular mechanism of CJJYAS in improving synaptic damage of vHPC neurons might be related to the regulation of synaptic remodeling-related signals such as NR/CaMKⅡ and MK2/cofilin. In conclusion, this research confirms that CJJYAS effectively regulates the abnormal ACC-vHPC glutaminergic neural circuit and alleviates the synaptic remodeling of vHPC glutaminergic neurons in depressed rats, and the molecular mechanism might be associated with the regulation of synapse-related NR/CaMKⅡ and MK2/cofilin signaling pathways, which may be the crucial mechanism of its antidepressant effect.


Asunto(s)
Depresión , Medicamentos Herbarios Chinos , Giro del Cíngulo , Hipocampo , Neuronas , Ratas Sprague-Dawley , Animales , Ratas , Masculino , Neuronas/metabolismo , Hipocampo/metabolismo , Depresión/metabolismo , Depresión/fisiopatología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Giro del Cíngulo/metabolismo , Giro del Cíngulo/fisiopatología , Sinapsis/metabolismo , Plasticidad Neuronal , Humanos
9.
Theor Appl Genet ; 137(6): 128, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733405

RESUMEN

KEY MESSAGE: Discovery of Rht27, a dwarf gene in wheat, showed potential in enhancing grain yield by reducing plant height. Plant height plays a crucial role in crop architecture and grain yield, and semi-dwarf Reduced Height (Rht) alleles contribute to lodging resistance and were important in "Green Revolution." However, the use of these alleles is associated with some negative side effects in some environments, such as reduced coleoptile length, low nitrogen use efficiency, and reduced yield. Therefore, novel dwarf gene resources are needed to pave an alternative route to overcome these side effects. In this study, a super-dwarf mutant rht27 was obtained by the mutagenesis of G1812 (Triticum urartu, the progenitor of the A sub-genome of common wheat). Genetic analysis revealed that the dwarf phenotype was regulated by a single recessive genetic factor. The candidate region for Rht27 was narrowed to a 1.55 Mb region on chromosome 3, within which we found two potential candidate genes that showed polymorphisms between the mutant and non-mutagenized G1812. Furthermore, the natural variants and elite haplotypes of the two candidates were investigated in a natural population of common wheat. The results showed that the natural variants affect grain yield components, and the dwarf haplotypes show the potential in improving agronomic traits and grain yield. Although the mutation in Rht27 results in severe dwarf phenotype in T. urartu, the natural variants in common wheat showed desirable phenotype, which suggests that Rht27 has the potential to improve wheat yield by utilizing its weak allelic mutation or fine-tuning its expression level.


Asunto(s)
Genes de Plantas , Triticum , Alelos , Mapeo Cromosómico , Haplotipos , Fenotipo , Triticum/genética , Triticum/crecimiento & desarrollo
10.
PLoS One ; 19(5): e0302068, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38758945

RESUMEN

The electric power sector is the primary contributor to carbon emissions in China. Considering the context of dual carbon goals, this paper examines carbon emissions within China's electricity sector. The research utilizes the LMDI approach for methodological rigor. The results show that the cumulative contribution of economies scale, power consumption factors and energy structure are 114.91%, 85.17% and 0.94%, which contribute to the increase of carbon emissions, the cumulative contribution of power generation efficiency and ratio of power dissipation to generation factor are -19.15% and -0.01%, which promotes the carbon reduction. The decomposition analysis highlights the significant influence of economic scale on carbon emissions in the electricity industry, among the seven factors investigated. Meanwhile, STIRPAT model, Logistic model and GM(1,1) model are used to predict carbon emissions, the average relative error between actual carbon emissions and the predicted values are 0.23%, 8.72% and 7.05%, which indicates that STIRPAT model is more suitable for medium- to long-term predictions. Based on these findings, the paper proposes practical suggestions to reduce carbon emissions and achieve the dual carbon goals of the power industry.


Asunto(s)
Carbono , Electricidad , China , Carbono/análisis , Industrias , Centrales Eléctricas , Modelos Teóricos
11.
Research (Wash D C) ; 7: 0359, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694199

RESUMEN

Porous substrates act as open "interfacial reactors" during the synthesis of polyamide composite membranes via interfacial polymerization. However, achieving a thin and dense polyamide nanofilm with high permeance and selectivity is challenging when using a conventional substrate with uniform wettability. To overcome this limitation, we propose the use of Janus porous substrates as confined interfacial reactors to decouple the local monomer concentration from the total monomer amount during interfacial polymerization. By manipulating the location of the hydrophilic/hydrophobic interface in a Janus porous substrate, we can precisely control the monomer solution confined within the hydrophilic layer without compromising its concentration. The hydrophilic surface ensures the uniform distribution of monomers, preventing the formation of defects. By employing Janus substrates fabricated through single-sided deposition of polydopamine/polyethyleneimine, we significantly reduce the thickness of the polyamide nanofilms from 88.4 to 3.8 nm by decreasing the thickness of the hydrophilic layer. This reduction leads to a remarkable enhancement in water permeance from 7.2 to 52.0 l/m2·h·bar while still maintaining ~96% Na2SO4 rejection. The overall performance of this membrane surpasses that of most reported membranes, including state-of-the-art commercial products. The presented strategy is both simple and effective, bringing ultrapermeable polyamide nanofilms one step closer to practical separation applications.

12.
Int J Biol Macromol ; : 132755, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38821295

RESUMEN

Interferon-induced transmembrane 3 (IFITM3) is a membrane-associated protein that exhibits antiviral activities against a wide range of viruses through interactions with other cellular and viral proteins. However, knowledge of the mechanisms of IFITM3 in Porcine deltacoronavirus (PDCoV) infection has been lacking. In this study, we demonstrate that IFN-α treatment induces the upregulation of IFITM3 activity and thus attenuates PDCoV infection. PDCoV replication is inhibited in a dose-dependent manner by IFITM3 overexpression. To clarify the novel roles of IFITM3 during PDCoV infection, proteins that interact with IFITM3 were screened by TAP/MS in an ST cell line stably expressing IFITM3 via a lentivirus. We identified known and novel candidate IFITM3-binding proteins and analyzed the protein complexes using GO annotation, KEGG pathway analysis, and protein interaction network analysis. A total of 362 cellular proteins associate with IFITM3 during the first 24 h post-infection. Of these proteins, the relationship between IFITM3 and Rab9a was evaluated by immunofluorescence colocalization analysis using confocal microscopy. IFITM3 partially colocalized with Rab9a and Rab9a exhibited enhanced colocalization following PDCoV infection. We also demonstrated that IFITM3 interacts specifically with Rab9a. Our results considerably expand the protein networks of IFITM3, suggesting that IFITM3 participates in multiple cellular processes during PDCoV infection.

14.
Anal Sci ; 40(7): 1331-1338, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38607597

RESUMEN

A fluorescent immunosorbent assay incorporating signal amplification away from the surface of spherical nucleic acid (SNA) was developed for the detection of chloramphenicol (CAP). Through the conjugation of antibodies and poly-adenine (polyA) DNA onto the surface of gold nanoparticles (AuNPs), the fabrication of the nano-immunoprobe was achieved in a more straightforward and cost-effective manner. Moreover, a strategy utilizing the hybridization chain reaction (HCR) in the amplification step was devised, with particular attention given to the enzyme inhibition associated with SNA. The results demonstrated good performance on CAP detection with a linear range of 0.01-5 ng/L with a detection limit of 0.005 ng/L. The significance of this work mainly lies in the polyA-SNA-based immunoprobe and the thoughtful design to prevent enzyme inhibition.


Asunto(s)
Cloranfenicol , Oro , Nanopartículas del Metal , Cloranfenicol/análisis , Oro/química , Nanopartículas del Metal/química , Poli A/química , Inmunoensayo/métodos , Límite de Detección
15.
Adv Mater ; 36(24): e2400075, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38597782

RESUMEN

Designing nanocomposite hydrogels with oriented nanosheets has emerged as a promising toolkit to achieve preferential performances that go beyond their disordered counterparts. Although current fabrication strategies via electric/magnetic force fields have made remarkable achievements, they necessitate special properties of nanosheets and suffer from an inferior orientation degree of nanosheets. Herein, a facile and universal approach is discovered to elaborate MXene-based nanocomposite hydrogels with highly oriented, heterogeneous architecture by virtue of supergravity to replace conventional force fields. The key to such architecture is to leverage bidirectional, force-tunable attributes of supergravity containing coupled orthogonal shear and centrifugal force field for steering high-efficient movement, pre-orientation, and stacking of MXene nanosheets in the bottom. Such a synergetic effect allows for yielding heterogeneous nanocomposite hydrogels with a high-orientation MXene-rich layer (orientation degree, f = 0.83) and a polymer-rich layer. The authors demonstrate that MXene-based nanocomposite hydrogels leverage their high-orientation, heterogeneous architecture to deliver an extraordinary electromagnetic interference shielding effectiveness of 55.2 dB at 12.4 GHz yet using a super-low MXene of 0.3 wt%, surpassing most hydrogels-based electromagnetic shielding materials. This versatile supergravity-steered strategy can be further extended to arbitrary nanosheets including MoS2, GO, and C3N4, offering a paradigm in the development of oriented nanocomposites.

16.
Eur J Pharmacol ; 972: 176557, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38574839

RESUMEN

Cerebral ischemia-reperfusion injury (CIRI) can induce massive death of ischemic penumbra neurons via oxygen burst, exacerbating brain damage. Parthanatos is a form of caspase-independent cell death involving excessive activation of PARP-1, closely associated with intense oxidative stress following CIRI. 4'-O-methylbavachalcone (MeBavaC), an isoprenylated chalcone component in Fructus Psoraleae, has potential neuroprotective effects. This study primarily investigates whether MeBavaC can act on SIRT3 to alleviate parthanatos of ischemic penumbra neurons induced by CIRI. MeBavaC was oral gavaged to the middle cerebral artery occlusion-reperfusion (MCAO/R) rats after occlusion. The effects of MeBavaC on cerebral injury were detected by the neurological deficit score and cerebral infarct volume. In vitro, PC-12 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R), and assessed cell viability and cell injury. Also, the levels of ROS, mitochondrial membrane potential (MMP), and intracellular Ca2+ levels were detected to reflect mitochondrial function. We conducted western blotting analyses of proteins involved in parthanatos and related signaling pathways. Finally, the exact mechanism between the neuroprotection of MeBavaC and parthanatos was explored. Our results indicate that MeBavaC reduces the cerebral infarct volume and neurological deficit scores in MCAO/R rats, and inhibits the decreased viability of PC-12 cells induced by OGD/R. MeBavaC also downregulates the expression of parthanatos-related death proteins PARP-1, PAR, and AIF. However, this inhibitory effect is weakened after the use of a SIRT3 inhibitor. In conclusion, the protective effect of MeBavaC against CIRI may be achieved by inhibiting parthanatos of ischemic penumbra neurons through the SIRT3-PARP-1 axis.


Asunto(s)
Chalconas , Fármacos Neuroprotectores , Parthanatos , Ratas Sprague-Dawley , Daño por Reperfusión , Sirtuinas , Animales , Ratas , Masculino , Chalconas/farmacología , Chalconas/uso terapéutico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Daño por Reperfusión/metabolismo , Parthanatos/efectos de los fármacos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/patología , Accidente Cerebrovascular Isquémico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Células PC12 , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/patología , Neuronas/metabolismo , Calcio/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/complicaciones , Supervivencia Celular/efectos de los fármacos , Sirtuina 3/metabolismo , Sirtuina 3/genética , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo
17.
Appl Environ Microbiol ; 90(5): e0197423, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38619269

RESUMEN

17ß-estradiol (E2) is a natural endocrine disruptor that is frequently detected in surface and groundwater sources, thereby threatening ecosystems and human health. The newly isolated E2-degrading strain Sphingomonas colocasiae C3-2 can degrade E2 through both the 4,5-seco pathway and the 9,10-seco pathway; the former is the primary pathway supporting the growth of this strain and the latter is a branching pathway. The novel gene cluster ean was found to be responsible for E2 degradation through the 4,5-seco pathway, where E2 is converted to estrone (E1) by EanA, which belongs to the short-chain dehydrogenases/reductases (SDR) superfamily. A three-component oxygenase system (including the P450 monooxygenase EanB1, the small iron-sulfur protein ferredoxin EanB2, and the ferredoxin reductase EanB3) was responsible for hydroxylating E1 to 4-hydroxyestrone (4-OH-E1). The enzymatic assay showed that the proportion of the three components is critical for its function. The dioxygenase EanC catalyzes ring A cleavage of 4-OH-E1, and the oxidoreductase EanD is responsible for the decarboxylation of the ring A-cleavage product of 4-OH-E1. EanR, a TetR family transcriptional regulator, acts as a transcriptional repressor of the ean cluster. The ean cluster was also found in other reported E2-degrading sphingomonads. In addition, the novel two-component monooxygenase EanE1E2 can open ring B of 4-OH-E1 via the 9,10-seco pathway, but its encoding genes are not located within the ean cluster. These results refine research on genes involved in E2 degradation and enrich the understanding of the cleavages of ring A and ring B of E2.IMPORTANCESteroid estrogens have been detected in diverse environments, ranging from oceans and rivers to soils and groundwater, posing serious risks to both human health and ecological safety. The United States National Toxicology Program and the World Health Organization have both classified estrogens as Group 1 carcinogens. Several model organisms (proteobacteria) have established the 4,5-seco pathway for estrogen degradation. In this study, the newly isolated Sphingomonas colocasiae C3-2 could degrade E2 through both the 4,5-seco pathway and the 9,10-seco pathway. The novel gene cluster ean (including eanA, eanB1, eanC, and eanD) responsible for E2 degradation by the 4,5-seco pathway was identified; the novel two-component monooxygenase EanE1E2 can open ring B of 4-OH-E1 through the 9,10-seco pathway. The TetR family transcriptional regulator EanR acts as a transcriptional repressor of the ean cluster. The cluster ean was also found to be present in other reported E2-degrading sphingomonads, indicating the ubiquity of the E2 metabolism in the environment.


Asunto(s)
Biodegradación Ambiental , Estradiol , Familia de Multigenes , Sphingomonas , Sphingomonas/metabolismo , Sphingomonas/genética , Estradiol/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Disruptores Endocrinos/metabolismo , Filogenia
18.
World J Gastrointest Oncol ; 16(3): 933-944, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38577453

RESUMEN

BACKGROUND: Transanal endoscopic intersphincteric resection (ISR) surgery currently lacks sufficient clinical research and reporting. AIM: To investigate the clinical effectiveness of transanal endoscopic ISR, in order to promote the clinical application and development of this technique. METHODS: This study utilized a retrospective case series design. Clinical and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were included. All patients underwent transanal endoscopic ISR as the surgical approach. We conducted this study to determine the perioperative recovery status, postoperative complications, and pathological specimen characteristics of this group of patients. RESULTS: This study included 45 eligible patients, with no perioperative mortalities. The overall incidence of early complications was 22.22%, with a rate of 4.44% for Clavien-Dindo grade ≥ III events. Two patients (4.4%) developed anastomotic leakage after surgery, including one case of grade A and one case of grade B. Postoperative pathological examination confirmed negative circumferential resection margins and distal resection margins in all patients. The mean distance between the tumor lower margin and distal resection margin was found to be 2.30 ± 0.62 cm. The transanal endoscopic ISR procedure consistently yielded high quality pathological specimens. CONCLUSION: Transanal endoscopic ISR is safe, feasible, and provides a clear anatomical view. It is associated with a low incidence of postoperative complications and favorable pathological outcomes, making it worth further research and application.

20.
Front Immunol ; 15: 1331486, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38510244

RESUMEN

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by swollen joints, discomfort, stiffness, osteoporosis, and reduced functionality. Genetics, smoking, dust inhalation, high BMI, and hormonal and gut microbiota dysbiosis are all likely causes of the onset or development of RA, but the underlying mechanism remains unknown. Compared to healthy controls, patients with RA have a significantly different composition of gut microbiota. It is well known that the human gut microbiota plays a key role in the initiation, maintenance, and operation of the host immune system. Gut microbiota dysbiosis has local or systematic adverse effects on the host immune system, resulting in host susceptibility to various diseases, including RA. Studies on the intestinal microbiota modulation and immunomodulatory properties of probiotics have been reported, in order to identify their potential possibility in prevention and disease activity control of RA. This review summarized current studies on the role and potential mechanisms of gut microbiota in the development and progression of RA, as well as the preventative and therapeutic effects and potential mechanisms of probiotics on RA. Additionally, we proposed the challenges and difficulties in the application of probiotics in RA, providing the direction for the research and application of probiotics in the prevention of RA.


Asunto(s)
Artritis Reumatoide , Microbioma Gastrointestinal , Probióticos , Humanos , Disbiosis/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Sistema Inmunológico , Probióticos/uso terapéutico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...