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1.
PeerJ ; 12: e17618, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948218

RESUMEN

Leaf inclination angle (LIA) and tillering impact the winter wheat (Triticum aestivum L.) population canopy structure. Understanding their effects on water use (WU) parameters and yield can guide water-saving strategies through population control. In this study, six near-isogenic lines (NILs) and their parents were selected as materials. These special materials were characterized by varying tillering at the current sowing density, a similar genetic background, and, particularly, a gradient in mean flag leaf LIA. The investigation focused on the jointing to early grain-filling stage, the peak water requirement period of wheat crops. Population-scale transpiration (PT) and evaporation from the soil surface (E) were partitioned from total evapotranspiration (ET) by the means of micro-lysimeters. The results showed decreased PT, E, and ET with increased population density (PD) within a narrow density range derived from varying tillering across genotypes. Significant correlations existed between PD and ET, E, and PT, especially in the wettest 2017-2018 growing season. Within such narrow PD range, all the correlations between WU parameters and PD were negative, although some correlations were not statistically significant, thereby suggesting the population structure's predominant impact. No significant correlation existed between LIA and both ET and PT within the LIA range of 35°-65°. However, significant correlations occurred between LIA and E in two growing seasons. Genotypes with similar LIA but different PD produced varied ET; while with similar PD, the four pairs of genotypes with different LIA each consumed similar ET, thus highlighting PD's more crucial role in regulating ET. The yield increased with higher LIA, and showed a significant correlation, emphasizing the LIA's significant effect on yield. However, no correlation was observed with PD, indicating the minor effect of tillering at the current sowing density. Therefore these results might offer valuable insights for breeding water-saving cultivars and optimizing population structures for effective field water conservation.


Asunto(s)
Hojas de la Planta , Transpiración de Plantas , Suelo , Triticum , Triticum/genética , Triticum/fisiología , Triticum/crecimiento & desarrollo , Hojas de la Planta/fisiología , Suelo/química , Estaciones del Año , Agua/metabolismo , Genotipo
2.
Chem Commun (Camb) ; 60(51): 6536-6539, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38841891

RESUMEN

Presented herein is the synthesis of diversely functionalized pyrrolizines from the reaction of N-alkoxycarbamoyl pyrroles with CF3-ynones. The formation of the product is based on a C-H bond activation-initiated cascade process including N-alkoxycarbamoyl group-directed alkenylation of the pyrrole scaffold followed by simultaneous intramolecular nucleophilic addition along with cleavage and transfer of the directing group. By taking advantage of the rich chemistry of the transferred alkoxycarbamoyl moiety, the products could be transformed into a series of structurally and biologically interesting pyrrolizine derivatives. To our knowledge, this is the first example in which the N-alkoxycarbamoyl unit acted as a transferable and transformable directing group for the divergent synthesis of pyrrolizines.

3.
Brain Stimul ; 17(3): 713-720, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38839040

RESUMEN

BACKGROUND: Recent studies indicate that both prefrontal and visual regions play critical roles in visual working memory (VWM), with prefrontal regions mainly associated with executive functions, and visual cortices linked to representations of memory contents. VWM involves the selective filtering of irrelevant information, yet the specific contributions of the prefrontal regions and visual cortex in this process remain unclear. OBJECTIVE: To understand the dynamic causal roles of prefrontal and visual regions in VWM. METHODS: The differentiation of VWM components was achieved using a computational model that incorporated a swap rate for non-target stimuli. Single-pulse magnetic transcranial stimulation (spTMS) was delivered to the early visual cortex (EVC) and the inferior frontal junction (IFJ) across different phases of an orientation recall task that with or without distractors. RESULTS: Our results indicate that spTMS over the EVC and IFJ influences VWM particularly when distractors are present. VWM precision can be impacted by spTMS applied to either region during the early retention, while spTMS effect is especially prominent when EVC is stimulated during the late retention phase and when directed at the ipsilateral EVC. Conversely, the probability of accurately recalling the target exhibited comparable patterns when spTMS was administered to either the EVC or IFJ. CONCLUSIONS: We highlight the "sensory recruitment" of VWM characterized by critical involvement of EVC particularly in the information-filtering process within VWM. The maintenance of memory content representations necessitates ongoing communication between the EVC and IFJ throughout the entirety of the VWM process in a dynamic pattern.


Asunto(s)
Memoria a Corto Plazo , Estimulación Magnética Transcraneal , Corteza Visual , Percepción Visual , Humanos , Memoria a Corto Plazo/fisiología , Estimulación Magnética Transcraneal/métodos , Corteza Visual/fisiología , Percepción Visual/fisiología , Masculino , Adulto , Femenino , Corteza Prefrontal/fisiología , Recuerdo Mental/fisiología , Adulto Joven
4.
Chemosphere ; 360: 142339, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38754488

RESUMEN

The environmental burden due to industrial activities has been quite observable in the last few years, with heavy metals (HMs) like lead, cadmium, and arsenic inducing serious perturbations to the microbial ecosystem of groundwater. Studies carried out in North China, a region known for interconnection of industrial and groundwater systems, sought to explore the natural mechanisms of adaptation of microbes to groundwater contamination. The results showed that heavy metals permeate from surface increased the diversity and abundance of microbial communities in groundwater, producing an average decrease of 40.84% and 34.62% in the relative abundance of Bacteroidetes and Proteobacteria in groundwater, respectively. Meanwhile, the key environmental factors driving the evolution of microbial communities shift from groundwater nutrients to heavy metals, which explained 50.80% of the change in the microbial community composition. Microbial indicators are more sensitive to HMs pollution and could accurately identify industrial area where HMs permeation occurred and other extraneous pollutants. The phylum Bacteroidetes could act as appropriate indicators for the identification. Significant genera that were identified, being Mesorhizobium, Clostridium, Bacillus and Mucilaginibacter, were found to play important roles in the microbial network in terms of the potential to assist in groundwater clean-up. Notably, pollution from heavy metals has diminished the effectiveness and resilience of microbial communities in groundwater, thereby heightening the susceptibility of these normally stable microbial ecosystems. These findings offer new perspectives on how to monitor and detect groundwater pollution, and provide scientific guidance for developing suitable remediation methods for groundwater contaminated with heavy metals. Future research is essential explore the application of metal-tolerant or resistant bacteria in bioremediation strategies to rehabilitate groundwater systems contaminated by HMs.


Asunto(s)
Monitoreo del Ambiente , Agua Subterránea , Metales Pesados , Contaminantes Químicos del Agua , Metales Pesados/análisis , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo , Agua Subterránea/química , Agua Subterránea/microbiología , China , Monitoreo del Ambiente/métodos , Microbiota/efectos de los fármacos , Bacterias/metabolismo , Bacterias/efectos de los fármacos , Bacteroidetes , Industrias , Ecosistema
5.
J Org Chem ; 89(11): 7828-7842, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38773933

RESUMEN

Presented herein is a novel synthesis of CF3-substituted pyrrolo[1,2-a]indole derivatives based on the cascade reactions of N-alkoxycarbamoyl indoles with CF3-ynones. Mechanistically, the formation of a product involves a tandem process initiated by Rh(III)-catalyzed and N-alkoxycarbamoyl group-directed regioselective C2-H alkenylation of the indole scaffold followed by in situ removal of the directing group and intramolecular N-nucleophilic addition/annulation under one set of reaction conditions. To our knowledge, this is the first example in which a N-alkoxycarbamoyl unit initially acts as a directing group for C2-H functionalization of the indole scaffold and is then removed to provide the required reactive NH-moiety for subsequent intramolecular condensation. Moreover, the products thus obtained could be conveniently transformed into structurally and biologically attractive cycloheptenone fused indole derivatives through an acid-promoted cascade transformation. In addition, studies on the activity of selected products against human cancer cell lines demonstrated their potential as lead compounds for the development of novel anticancer drugs.

6.
Arch Microbiol ; 206(6): 249, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713385

RESUMEN

Escherichia coli (E. coli) can induce severe clinical bovine mastitis, which is to blame for large losses experienced by dairy farms. Macrophage polarization into various states is in response to pathogen infections. Lycopene, a naturally occurring hydrocarbon carotenoid, relieved inflammation by controlling M1/M2 status of macrophages. Thus, we wanted to explore the effect of lycopene on polarization states of macrophages in E. coli-induced mastitis. Macrophages were cultivated with lycopene for 24, before E. coli inoculation for 6 h. Lycopene (0.5 µmol/L) significantly enhanced cell viabilities and significantly reduced lactic dehydrogenase (LDH) levels in macrophages, whereas 2 and 3 µmol/L lycopene significantly enhanced LDH activities. Lycopene treatment significantly reduced the increase in LDH release, iNOS, CD86, TNF-α, IL-1ß and phosphatase and tensin homolog (PTEN) expressions in E. coli group. 0.5 µmol/L lycopene significantly increased E. coli-induced downregulation of CD206, arginase I (ARG1), indoleamine 2,3-dioxygenase (IDO), chitinase 3-like 3 (YM1), PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, jumonji domain-containing protein-3 (JMJD3) and interferon regulatory factor 4 (IRF4) levels. Moreover, Ginkgolic acid C17:1 (a specific PTEN inhibitor), 740YPDGFR (a specific PI3K activator), SC79 (a specific AKT activator) or CHPG sodium salt (a specific NF-κB activator) significantly decreased CD206, AGR1, IDO and YM1 expressions in lycopene and E. coli-treated macrophages. Therefore, lycopene increased M2 macrophages via inhibiting NOTCH1-PI3K-mTOR-NF-κB-JMJD3-IRF4 pathway in response to E. coli infection in macrophages. These results contribute to revealing the pathogenesis of E. coli-caused bovine mastitis, providing the new angle of the prevention and management of mastitis.


Asunto(s)
Infecciones por Escherichia coli , Escherichia coli , Licopeno , Macrófagos , Transducción de Señal , Animales , Bovinos , Femenino , Ratones , Línea Celular , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/inmunología , Factores Reguladores del Interferón/metabolismo , Factores Reguladores del Interferón/genética , Licopeno/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/microbiología , Macrófagos/inmunología , Macrófagos/metabolismo , Mastitis Bovina/microbiología , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Receptor Notch1/metabolismo , Receptor Notch1/genética , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo
7.
Org Lett ; 26(15): 3091-3096, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38567810

RESUMEN

Presented herein is a novel synthesis of pharmaceutically privileged spiroindoline derivatives via cascade reactions of N-methyl-N-nitrosoanilines with diazo homophthalimides. A group of mechanistic studies disclosed that the formation of product involves an unusual reaction mode of N-methyl-N-nitrosoaniline featuring an initial C(sp2)-H bond activation/alkylation followed by a C(sp3)-H bond activation/spiroannulation. To our knowledge, this is the first example in which N-methyl-N-nitrosoaniline acts as a C3N1 synthon to accomplish formal [4+1] spiroannulation with the participation of the N-methyl unit rather than the previously reported C2N1 synthon to undergo formal [3+2] annulation without the participation of the N-methyl unit. In general, this newly developed synthetic protocol features simple and readily accessible starting materials, valuable products, unique reaction mechanism, high efficiency and atom-economy, excellent compatibility with diverse functional groups, and ready scalability.

8.
J Org Chem ; 89(9): 6292-6305, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38625738

RESUMEN

Presented herein is an effective and concise synthesis of acyl cyclopentaquinolinone derivatives via the cascade reactions of N-(o-ethynylaryl)acrylamides with α-diazo carbonyl compounds. The formation of product involves a visible light-induced radical formation from α-diazo carbonyl compound followed by its addition onto the acrylamide moiety to trigger double radical annulation, single-electron oxidation, and ß-elimination. To our knowledge, this is the first example in which the cyclopentaquinolinone scaffold was constructed along with the introduction of an acyl group under visible light irradiation conditions. Compared with literature methods for similar purpose, this newly developed protocol has advantages such as readily accessible substrates, mild reaction conditions, valuable products, concise synthetic procedure, and high sustainability. With all these merits, this method is expected to find wide applications in the construction of related acyl heterocyclic skeletons.

9.
Front Pharmacol ; 15: 1324892, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38487164

RESUMEN

As an inflammatory disease with a disrupted immune system, cytokine disorders in atopic dermatitis (AD) are closely related to the abnormal activation of JAK-STAT signal pathway. The critical relevance of the JAK-STAT signaling pathway to the pathogenesis of AD provides a strong rationale for JAK inhibitor research. Baricitinib, a small-molecule oral JAK inhibitor, has been proven to inhibit JAK-STAT signaling in a variety of diseases, including AD. It is currently available in China for off-label use. However, its efficacy in China and its mechanism are rarely reported. In our study, we found that the immune status of patients with moderate and severe AD was hyperactive. Among the 49 known immunotherapy targets, JAK1 and JAK2 genes on lymphocytes of AD patients were significantly upregulated, which was closely related to the symptom severity in moderate and severe AD patients. Baricitinib can improve immune hyperresponsiveness and clinical symptoms in moderate and severe AD by inhibiting the activation of Th2 cell subsets and the secretion of Th2-type cytokines through MAPK, mTOR and PI3K-Akt signaling pathways, providing an important theoretical basis for clinical off-label use of Baricitinib to treat moderate and severe AD.

10.
Mol Breed ; 44(4): 29, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38549701

RESUMEN

The chloroplast serves as the primary site of photosynthesis, and its development plays a crucial role in regulating plant growth and morphogenesis. The Pentatricopeptide Repeat Sequence (PPR) proteins constitute a vast protein family that function in the post-transcriptional modification of RNA within plant organelles. In this study, we characterized mutant of rice with pale green leaves (pgl3a). The chlorophyll content of pgl3a at the seedling stage was significantly reduced compared to the wild type (WT). Transmission electron microscopy (TEM) and quantitative PCR analysis revealed that pgl3a exhibited aberrant chloroplast development compared to the wild type (WT), accompanied by significant alterations in gene expression levels associated with chloroplast development and photosynthesis. The Mutmap analysis revealed that a single base deletionin the coding region of Os03g0136700 in pgl3a. By employing CRISPR/Cas9 mediated gene editing, two homozygous cr-pgl3a mutants were generated and exhibited a similar phenotype to pgl3a, thereby confirming that Os03g0136700 was responsible for pgl3a. Consequently, it was designated as OsPGL3A. OsPGL3A belongs to the DYW-type PPR protein family and is localized in chloroplasts. Furthermore, we demonstrated that the RNA editing efficiency of rps8-182 and rpoC2-4106, and the splicing efficiency of ycf3-1 were significantly decreased in pgl3a mutants compared to WT. Collectively, these results indicate that OsPGL3A plays a crucial role in chloroplast development by regulating the editing and splicing of chloroplast genes in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01468-7.

11.
Eur J Med Res ; 29(1): 168, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38475859

RESUMEN

OBJECTIVE: To analyze the risk factors affecting psychiatric behavior and study the psychobehavioral conditions of children with epilepsy. METHOD: We randomly selected and enrolled 294 children with epilepsy who visited and were hospitalized in the pediatric clinic of Hebei General Hospital between January 2017 and January 2022, as the study participants. We comprehensively assessed their cognitive functions using the Gesell development schedule or Wechsler Intelligence Scales. The participants were divided into the study group (n = 123) with cognitive impairment and the control group (n = 171) with normal cognitive functions, for analysis. RESULTS: There were statistically significant differences between the two groups in disease course, frequency of epilepsy, status epilepticus, and the number of antiseizure medications (ASMs) used (P < 0.05), while there were no statistically significant differences in age, gender, age of onset, form of onset, interictal epileptiform discharge, history of febrile convulsion, and the time from onset to initial visit (P > 0.05). Based on multivariate logistic regression analysis, the course of disease, frequency of onset, status epilepticus and number of ASMs used were identified as high-risk factors for cognitive impairment in children with epilepsy. Similarly, early onset, long course of disease, known etiology, and combination of multiple drugs have a negative impact on behavioral problems, school education, and social adaptability. CONCLUSION: The course of disease, the frequency of onset, status epilepticus, and the number of ASMs used are high-risk factors for cognitive impairment in children with epilepsy, which can be prevented and controlled early. When selecting ASMs, their advantages and disadvantages should be weighed. Moreover, the availability of alternative treatment options must be considered. With the help of genomic technology, the causes of epilepsy should be identified as early as possible, and precision medicine and gene therapy for children with epilepsy should be actively developed.


Asunto(s)
Trastornos del Conocimiento , Epilepsia , Estado Epiléptico , Niño , Humanos , Cognición , Trastornos del Conocimiento/epidemiología , Comorbilidad , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Epilepsia/psicología , Estado Epiléptico/complicaciones , Masculino , Femenino
12.
Food Res Int ; 178: 113931, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38309903

RESUMEN

The comprehensive understanding of multi-scale structure of starch and how the structure regulates the pasting/digestion properties remain unclear. This work investigated the effects of γ-ray irradiation with different doses on multi-scale structure and pasting/digestion properties of potato starch. Results indicated that γ-ray at lower doses (<20 kGy) had little effect on micromorphology of starch, increased mainly the amylose content and the thickness of amorphous region while decreased crystallinity, double helix content and lamellar ordering. With the increase of dose, the internal structure of large granules was destroyed, resulting in the depolymerization of starch to form more short-chains and to reduce molecular weight. Meanwhile, amylose content decreased due to the depolymerization of amylose. The enhanced double helix content, crystallinity, lamellar ordering and structural compactness manifested the formation of the thicker and denser starch structure. These structure changes resulted in the decreased viscosity, the increased stability and anti- digestibility of paste.


Asunto(s)
Amilosa , Solanum tuberosum , Amilosa/química , Almidón/química , Viscosidad , Digestión
13.
Org Biomol Chem ; 22(12): 2324-2338, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38391295

RESUMEN

Spirocyclic skeletons are prevalent in natural products, pharmaceuticals and organic functional materials. Meanwhile, transition-metal-catalyzed C-H activation reactions have demonstrated unparalleled advantages such as high efficiency, excellent atom-economy, good chemoselectivity and regioselectivity for the formation of target organic molecules. In recent years, C-H activation reactions have been creatively utilized in the synthesis of spirocyclic compounds. This review summarizes the most recent progress made in C-H activation-initiated spiroannulation reactions and their applications in the construction of structurally diverse and biologically valuable spirocyclic scaffolds by using alkynes, diazo compounds, maleimides, alkenes, quinones and cyclopropenones as the coupling partners.

14.
Neurobiol Dis ; 191: 106402, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38184015

RESUMEN

Social dominance is a universal phenomenon among grouped animals that profoundly affects survival, health, and reproductive success by determining access to resources, and exerting a powerful influence on subsequent behavior. However, the understanding of pain and anxiety comorbidities in dominant or subordinate animals suffering from chronic pain is not well-defined. Here, we provide evidence that subordinate mice are more susceptible to pain-induced anxiety compared to dominant mice. We propose that the gut microbiota may play a mediating role in this mechanism. Our findings demonstrate that transplantation of fecal microbiota from subordinate mice with chronic inflammatory pain, but not dominant mice, into antibiotics-treated pseudo-germ-free mice significantly amplifies anxiety-like phenotypes, highlighting the critical involvement of gut microbiota in this behavioral response. Using chronic inflammatory pain model, we carried out 16S rRNA sequencing and untargeted metabolomic analyses to explore the relationship between microbiota and metabolites in a stable social hierarchy of mice. Interestingly, anxiety-like behaviors were directly associated with some microbial genera and metabolites, especially bile acid metabolism. Overall, we have demonstrated a close relationship between social status and anxiety susceptibility, highlighting the contributions of gut microbiota and the associated metabolites in the high-anxiety state of subordinate mice with chronic inflammatory pain.


Asunto(s)
Dolor Crónico , Microbioma Gastrointestinal , Ratones , Animales , Microbioma Gastrointestinal/genética , Depresión , ARN Ribosómico 16S , Jerarquia Social , Ansiedad
15.
Org Lett ; 26(4): 786-791, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38251835

RESUMEN

Presented herein is an unprecedented synthesis of naphtho[1',2':4,5]furo[3,2-b]pyridinones via Ir(III)-catalyzed C6/C5 dual C-H functionalization of N-pyridyl-2-pyridones with diazonaphthalen-2(1H)-ones. This protocol forms C-C and C-O bonds in one pot in which diazonaphthalen-2(1H)-ones serve as bifunctional reagents, providing both alkyl and aryloxy sources. To the best of our knowledge, this is the first example of an Ir(III)-catalyzed synthesis of the title compounds by using diazonaphthalen-2(1H)-ones as bifunctional substrates. Notably, this method features operational simplicity, good functional group tolerance, high efficiency, and high atom economy.

16.
J Org Chem ; 89(3): 1880-1897, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38252142

RESUMEN

Herein, we present an efficient synthesis of 1,7-fused indolines tethered with a spiroindolinonyl moiety through the cascade reaction of indolin-1-yl(aryl)methanimines with diazo oxindoles. To the best of our knowledge, this is the first example in which 1,7-fused indoline skeleton was constructed along with the simultaneous introduction of a spiro element initiated by the C-H bond activation of indoline. In forming the title product, the indoline substrate and the diazo coupling partner demonstrated an unprecedented reaction pattern in which the latter acts as a C1 synthon to participate in the construction of the spirocyclic scaffold through the reductive elimination of a key seven-membered Ru(II) species by using air as an effective and sustainable oxidant to regenerate the active catalyst. Moreover, studies on the cytotoxicity of selected products against several human cancer cell lines demonstrated their potential as lead compounds for the development of anticancer drugs. With notable features such as simple and economical substrates, pharmaceutically valuable products with sophisticated spirocyclic skeleton, mild reaction conditions, cost-free and sustainable oxidants, high efficiency, excellent compatibility with diverse functional groups, and scalability, this method is expected to find wide applications in related areas.

17.
Mol Neurobiol ; 61(1): 308-325, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37607993

RESUMEN

Microglia are immunocompetent cells in the central nervous system. Following cerebral ischemia, microglia will be rapidly activated and undergo proliferation, morphological transformation, and changes in gene expression and function. At present, the regulatory mechanisms of microglial activation following ischemia remain largely unclear. In this study, we took advantage of CX3CR1GFP/+ fluorescent mice and a global cerebral ischemia-reperfusion model to investigate the mechanisms of microglial activation following different degrees of global ischemia. Our results showed that the proliferation of microglia was gated by the degree of ischemia. Marked microglial de-ramification and proliferation were observed after 60 min of ischemia but not in transient ischemia (20 min). Immunohistology, qRT-PCR, and Western blotting analysis showed that microglial activation was accompanied with a reduction in Wnt/ß-catenin signaling after cerebral ischemia. Downregulation of Wnt/ß-catenin signaling using Wnt antagonist XAV939 during 20 min ischemia promoted microglial de-ramification and proliferation. In contrast, enhancing Wnt/ß-catenin signaling using Wnt agonist LiCl during 60 min ischemia-reduced microglial de-ramification and proliferation. Importantly, we found that Wnt agonist inhibited inflammation in the ischemic brain and was conducive to animal behavioral recovery. Collectively, these data demonstrated that Wnt/ß-catenin signaling played a key role in microglial activation following cerebral ischemia, and regulating microglial activation may be a potential therapeutic strategy for the treatment of ischemic stroke.


Asunto(s)
Isquemia Encefálica , Microglía , Ratones , Animales , Microglía/metabolismo , beta Catenina/metabolismo , Isquemia Encefálica/patología , Vía de Señalización Wnt/fisiología , Infarto Cerebral/patología
18.
Brain Behav Immun ; 115: 64-79, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37793489

RESUMEN

CD38 is involved in immune responses, cell proliferation, and has been identified in the brain, where it is implicated in inflammation processes and psychiatric disorders. We hypothesized that dysfunctional CD38 activity in the brain may contribute to the pathogenesis of depression. To investigate the underlying mechanisms, we used a lipopolysaccharide (LPS)-induced depression-like model and conducted behavioral tests, molecular and morphological methods, along with optogenetic techniques. We microinjected adeno-associated virus into the hippocampal CA3 region with stereotaxic instrumentation. Our results showed a marked increase in CD38 expression in both the hippocampus and cortex of LPS-treated mice. Additionally, pharmacological inhibition and genetic knockout of CD38 effectively alleviated neuroinflammation, microglia activation, synaptic defects, and Sirt1/STAT3 signaling, subsequently improving depression-like behaviors. Moreover, optogenetic activation of glutamatergic neurons of hippocampal CA3 reduced the susceptibility of mice to depression-like behaviors, accompanied by reduced CD38 expression. We also found that (R)-ketamine, which displayed antidepressant effects, was linked to its anti-inflammatory properties by suppressing increased CD38 expression and reversing synaptic defects. In conclusion, hippocampal CD38 is closely linked to depression-like behaviors in an inflammation model, highlighting its potential as a therapeutic target for antidepressant development.


Asunto(s)
ADP-Ribosil Ciclasa 1 , Depresión , Ketamina , Animales , Ratones , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/metabolismo , Depresión/metabolismo , Hipocampo/metabolismo , Inflamación/metabolismo , Ketamina/farmacología , Ketamina/uso terapéutico , Ketamina/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , ADP-Ribosil Ciclasa 1/metabolismo
19.
Chemosphere ; 349: 140951, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38101485

RESUMEN

Salinity, a critical factor, could directly or indirectly affect the microbial community structure and diversity. Changes in salinity levels act as environmental filters that influence the transformation of key microbial species. This study investigates the adaptive characteristics of indigenous microflora in groundwater in relation to external organic pollutants under high salinity stress. A highly mineralized shallow groundwater in Northwest China was conducted as the study area, and six representative sampling points were chosen to explore the response of groundwater hydrochemical parameters and microflora, as well as to identify the tolerance mechanisms of indigenous microflora to combined pollution. The results revealed that the dominant genera found in high salinity groundwater contaminated with organic pollutants possess the remarkable ability to degrade such pollutants even under challenging high salinity conditions, including Halomonas, Pseudomonas, Halothiobacillus, Sphingomonas, Lutibacter, Aquabacterium, Thiomicrospira, Aequorivita, etc. The hydrochemical factors, including total dissolved solids (TDS), sulfide, nitrite, nitrate, oxidation reduction potential (ORP), NH3-N, Na, Fe, benzene series, phenols, and halogenated hydrocarbons, demonstrated a significant influence on microflora. High levels of sulphate and sulfide in groundwater can exhibit dual effects on microflora. On one hand, these compounds can inhibit the growth and metabolism of microorganisms. On the other hand, they can also serve as effective electron donors/receptors during the microbial degradation of organic pollutants. Microorganisms exhibit resilience to the inhibitory effects of high salinity and organic pollutants via a series of tolerance mechanisms, such as strengthening the extracellular membrane barrier, enhancing the synthesis of relevant enzymes, initiating novel biochemical reactions, improving cellular self-healing capabilities, responding to unfavorable environmental conditions by migration, and enhancing the S cycle for the microbial metabolism of organic pollutants.


Asunto(s)
Contaminantes Ambientales , Agua Subterránea , Contaminantes Químicos del Agua , Monitoreo del Ambiente , Salinidad , Contaminantes Químicos del Agua/análisis , Agua Subterránea/química , Sulfuros
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(11): 1143-1149, 2023 Nov 15.
Artículo en Chino | MEDLINE | ID: mdl-37990459

RESUMEN

OBJECTIVES: To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children. METHODS: A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes. RESULTS: There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05). CONCLUSIONS: The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.


Asunto(s)
Hormona de Crecimiento Humana , Niño , Humanos , Hormona de Crecimiento Humana/uso terapéutico , Hormona de Crecimiento Humana/farmacología , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Factor-23 de Crecimiento de Fibroblastos , Estudios Prospectivos , Trastornos del Crecimiento , Fosfatos/farmacología , Estatura
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