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1.
BMC Pediatr ; 24(1): 200, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38515059

RESUMEN

BACKGROUND: The results of disparate clinical studies indicate abnormally frequent cases of certain microorganisms in children with autism spectrum disorders (ASD). However, these data require clarification and systematization. The study aims to study the structure of the microbial profile in children with ASD and genetic folate cycle deficiency (GFCD) and consider differences in diagnostic approaches for identifying microorganisms of different types. METHODS: The study analyzed medical data from 240 children (187 boys and 63 girls) with GFCD aged 2 to 9 years. The children had clinical manifestations of ASD (the study group, SG). The control group (CG) included 53 clinically healthy children (37 boys and 16 girls) of the same age but without GFCD. Both groups of children were tested on active herpetic infections (HSV-1/2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8), ТТV, Streptococcus pyogenes, Candida albicans, Borrelia burgdorferi, Mycoplasma pneumoniae, Chlamydia pneumoniae, Yersinia enterocolitica, Toxoplasma gondii, congenital CMV neuroinfection and postnatal HSV-1/2 encephalitis. The testing used diagnostic methods specified in PubMed-indexed studies. RESULTS: In the SG, TTV was found in 196 children (82%), HHV-7 - in 172 (72%), HHV-6 - in 162 (68%), EBV - in 153 (64%), Streptococcus pyogenes - in 127 (53%), Candida albicans - in 116 (48%), Borrelia - in 107 (45%), Mycoplasma pneumoniae - in 94 (39%), Chlamydia pneumoniae - in 85 (35%), Yersinia entеrocolitica - in 71 (30%), Toxoplasma gondii - in 54 (23%), congenital CMV neuroinfection - in 26 (11%), and postnatal HSV-1/2 encephalitis - in 11 children (5% of cases) (p < p0.05; Z < Z0.05). In the SG, there was a higher microbial load in older children (p < p0.05; Z < Z0.05). No gender differences were found. CONCLUSIONS: The study described and characterized a specific abnormal microbial spectrum with a predominance of viral opportunistic agents in children with ASD associated with GFCD.


Asunto(s)
Trastorno del Espectro Autista , Infecciones por Citomegalovirus , Encefalitis , Infecciones por Herpesviridae , Herpesvirus Humano 6 , Masculino , Niño , Femenino , Humanos , Infecciones por Herpesviridae/diagnóstico , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/diagnóstico , Herpesvirus Humano 6/genética , Ácido Fólico
2.
J Biol Chem ; 297(5): 101345, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34717955

RESUMEN

Detection of thymidine analogues after their incorporation into replicating DNA represents a powerful tool for the study of cellular DNA synthesis, progression through the cell cycle, cell proliferation kinetics, chronology of cell division, and cell fate determination. Recent advances in the concurrent detection of multiple such analogues offer new avenues for the investigation of unknown features of these vital cellular processes. Combined with quantitative analysis, temporal discrimination of multiple labels enables elucidation of various aspects of stem cell life cycle in situ, such as division modes, differentiation, maintenance, and elimination. Data obtained from such experiments are critically important for creating descriptive models of tissue histogenesis and renewal in embryonic development and adult life. Despite the wide use of thymidine analogues in stem cell research, there are a number of caveats to consider for obtaining valid and reliable labeling results when marking replicating DNA with nucleotide analogues. Therefore, in this review, we describe critical points regarding dosage, delivery, and detection of nucleotide analogues in the context of single and multiple labeling, outline labeling schemes based on pulse-chase, cumulative and multilabel marking of replicating DNA for revealing stem cell proliferative behaviors, and determining cell cycle parameters, and discuss preconditions and pitfalls in conducting such experiments. The information presented in our review is important for rational design of experiments on tracking dividing stem cells by marking replicating DNA with thymidine analogues.


Asunto(s)
Ciclo Celular , Autorrenovación de las Células , Rastreo Celular , Replicación del ADN , Células Madre , Timidina , Animales , Humanos , Células Madre/citología , Células Madre/metabolismo , Timidina/análogos & derivados , Timidina/química , Timidina/farmacología
3.
Immunology ; 167(3): 443-450, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35866691

RESUMEN

The purpose of the present study is to evaluate the efficacy of combination immunotherapy with Propes and Inflamafertin in GDFC adults with natural killer (NK) and/or natural killer T-lymphocyte (NKT) cell deficiency. This single-centre, retrospective, controlled, non-randomized clinical trial analysed medical records of 212 adult GDFC patients aged 19-50 years (study group [SG]). SG received Propes at a dose of 2 ml intramuscularly every other day at night for three consecutive months and Inflamafertin at a dose of 2 ml IM every other day at night for three consecutive months in rotation with Propes. The control group involved 34 patients with GDFC who followed the same age and gender distribution pattern but did not receive immunotherapy. The number of NK cells reached the lower limit of normal in 95 out of 131 patients (72% of cases) with baseline deficiency of these lymphocytes. The average number of NK cells in the blood of SG patients almost doubled during the 3-month course of immunotherapy (P ˂ 0.05; Z ˂ Z0.05 ). However, it almost returned to initial levels 2 months following the discontinuation of the immunotherapeutic agents (P ˃ 0.05; Z ˃ Z0.05 ). Combination immunotherapy with Propes and Inflamafertin is an effective strategy for the treatment of immunodeficiency caused by GDFC in adult patients.


Asunto(s)
Células T Asesinas Naturales , Adulto , Ácido Fólico , Humanos , Inmunoterapia , Células Asesinas Naturales , Estudios Retrospectivos
4.
J Am Chem Soc ; 144(47): 21751-21762, 2022 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-36379028

RESUMEN

Lanthanides are important fission products in molten salt reactors, and understanding their structure and that of their mixtures is relevant to many scientific and technological problems including the recovery and separation of rare earth elements using molten salt electrolysis. The literature on molten salts and specifically on LaCl3 and LaCl3-NaCl mixtures is often fragmented, with different experiments and simulations coinciding in their explanation for certain structural results but contradicting or questioning for others. Given the very practical importance that actinide and lanthanide salts have for energy applications, it is imperative to arrive at a clear unified picture of their local and intermediate-range structure in the neat molten state and when mixed with other salts. This article aims to unequivocally answer a set of specific questions: is it correct to think of long-lived octahedral coordination structures for La3+? What is the nature as a function of temperature of networks and intermediate-range order particularly upon dilution of the trivalent ion salt? Is the so-called scattering first sharp diffraction peak (FSDP) for neat LaCl3 truly indicative of intermediate-range order? If so, why is there a new lower-q peak when mixed with NaCl? Are X-ray scattering and Raman spectroscopy results fully consistent and easily described by simulation results? We will show that answers to these questions require that we abandon the idea of a most prominent coordination state for M3+ ions and instead think of multiple competing coordination states in exchange due to significant thermal energy in the molten state.


Asunto(s)
Elementos de la Serie de los Lantanoides , Sales (Química) , Sales (Química)/química , Cloruro de Sodio , Iones/química , Temperatura
5.
Histochem Cell Biol ; 157(2): 239-250, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34757474

RESUMEN

Detection of synthetic thymidine analogues after their incorporation into replicating DNA during the S-phase of the cell cycle is a widely exploited methodology for evaluating proliferative activity, tracing dividing and post-mitotic cells, and determining cell-cycle parameters both in vitro and in vivo. To produce valid quantitative readouts for in vivo experiments with single intraperitoneal delivery of a particular nucleotide, it is necessary to determine the time interval during which a synthetic thymidine analogue can be incorporated into newly synthesized DNA, and the time by which the nucleotide is cleared from the blood serum. To date, using a variety of methods, only the bioavailability time of tritiated thymidine and 5-bromo-2'-deoxyuridine (BrdU) have been evaluated. Recent advances in double- and triple-S-phase labeling using 5-iodo-2'-deoxyuridine (IdU), 5-chloro-2'-deoxyuridine (CldU), and 5-ethynyl-2'-deoxyuridine (EdU) have raised the question of the bioavailability time of these modified nucleotides. Here, we examined their labeling kinetics in vivo and evaluated label clearance from blood serum after single intraperitoneal delivery to mice at doses equimolar to the saturation dose of BrdU (150 mg/kg). We found that under these conditions, all the examined thymidine analogues exhibit similar labeling kinetics and clearance rates from the blood serum. Our results indicate that all thymidine analogues delivered at the indicated doses have similar bioavailability times (approximately 1 h). Our findings are significant for the practical use of multiple S-phase labeling with any combinations of BrdU, IdU, CldU, and EdU and for obtaining valid labeling readouts.


Asunto(s)
Bromodesoxiuridina/metabolismo , Desoxiuridina/análogos & derivados , Gliburida/análogos & derivados , Timidina/metabolismo , Animales , Disponibilidad Biológica , Bromodesoxiuridina/administración & dosificación , Bromodesoxiuridina/sangre , Giro Dentado/metabolismo , Desoxiuridina/administración & dosificación , Desoxiuridina/sangre , Desoxiuridina/metabolismo , Gliburida/administración & dosificación , Gliburida/sangre , Gliburida/metabolismo , Inyecciones Intraperitoneales , Cinética , Ratones , Ratones Endogámicos C57BL , Timidina/administración & dosificación , Timidina/análogos & derivados
6.
Microbiol Immunol ; 66(4): 193-199, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35102619

RESUMEN

This study aimed to compare the efficacy of valaciclovir, valganciclovir, and artesunate in treating chronic reactivated human herpesvirus type 6 (HHV-6) and human herpesvirus type 7 (HHV-7) infection associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). From 255 patients (192 cases) with reactivated HHV-6 and HHV-7 infections (confirmed based on blood leukocyte PCR), valaciclovir, valganciclovir, or artesunate was administered at a dose of 3000, 900, and 100 mg/day, respectively, for 3 months (study group). The control group consisted of similar patients with ME/CFS (n = 63) not taking any antiviral drugs. The significance of differences was evaluated by Student's t-test and the nonparametric criterion-the number of Z-signs. Negative PCR results in patients with HHV-6 and HHV-7 treated with valaciclovir was achieved in 26% and 23% (first month), 34%, and 28% (second month), 37% and 34% of cases (third month), respectively (P < 0.05; Z < Z0.05 ). The same results with valganciclovir were obtained in 35% and 33% (first month), 44% and 39% (second month), 48% and 45% of cases (third month), but with artesunate in 44% and 41% (first month), 57% and 53% (second month), 68% and 63% of cases (third month), respectively (P < 0.05; Z < Z0.05 ). Artesunate is more effective than valganciclovir and valacyclovir in patients with ME/CFS with reactivated HHV-6 and HHV-7 infections.


Asunto(s)
Síndrome de Fatiga Crónica , Herpesvirus Humano 6 , Herpesvirus Humano 7 , Artesunato , Humanos , Valaciclovir/uso terapéutico , Valganciclovir/uso terapéutico
7.
Glycobiology ; 31(8): 959-974, 2021 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-33978736

RESUMEN

Elevated plasma levels of hyaluronic acid (HA) is a disease marker in liver pathology and other inflammatory disorders. Inhibition of HA synthesis with coumarin 4-methylumbelliferone (4MU) has a beneficial effect in animal models of fibrosis, inflammation, cancer and metabolic syndrome. 4MU is an active compound of approved choleretic drug hymecromone with low bioavailability and a broad spectrum of action. New, more specific and efficient inhibitors of hyaluronan synthases (HAS) are required. We have tested several newly synthesized coumarin compounds and commercial chitin synthesis inhibitors to inhibit HA production in cell culture assay. Coumarin derivative compound VII (10'-methyl-6'-phenyl-3'H-spiro[piperidine-4,2'-pyrano[3,2-g]chromene]-4',8'-dione) demonstrated inhibition of HA secretion by NIH3T3 cells with the half-maximal inhibitory concentration (IC50) = 1.69 ± 0.75 µΜ superior to 4MU (IC50 = 8.68 ± 1.6 µΜ). Inhibitors of chitin synthesis, etoxazole, buprofezin, triflumuron, reduced HA deposition with IC50 of 4.21 ± 3.82 µΜ, 1.24 ± 0.87 µΜ and 1.48 ± 1.44 µΜ, respectively. Etoxazole reduced HA production and prevented collagen fibre formation in the CCl4 liver fibrosis model in mice similar to 4MU. Bioinformatics analysis revealed homology between chitin synthases and HAS enzymes, particularly in the pore-forming domain, containing the proposed site for etoxazole binding.


Asunto(s)
Ácido Hialurónico , Himecromona , Animales , Quitina , Hialuronano Sintasas/metabolismo , Ácido Hialurónico/metabolismo , Himecromona/farmacología , Ratones , Células 3T3 NIH
8.
Angew Chem Int Ed Engl ; 60(49): 25688-25694, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34582075

RESUMEN

Perfluorinated covalent triazine frameworks (F-CTFs) have shown unique features and attractive performance in separation and catalysis. However, state-of-the-art F-CTFs synthesized via the ZnCl2 -promoted procedure have quite low fluorine contents due to C-F bond cleavage induced by chloride (a Lewis base) and the harsh conditions deployed (400-700 °C). Fabricating F-CTFs with high fluorine contents (>30 wt %) remains challenging. Herein, we present a low-temperature ionothermal approach (275 °C) to prepare F-CTFs, which is achieved via polymerization of tetrafluoroterephthalonitrile (TFPN) over the Lewis superacids, e.g., zinc triflimide [Zn(NTf2 )2 ] without side reactions. With low catalyst loading (equimolar), F-CTFs are afforded with high fluorine content (31 wt %), surface area up to 367 m2 g-1 , and micropores around 1.1 nm. The highly hydrophobic F-CTF-1 exhibits good capability to boost electroreduction of CO2 to CO, with faradaic efficiency of 95.7 % at -0.8 V and high current density (-141 mA cm-2 ) surpassing most of the metal-free electrocatalysts.

9.
Int J Mol Sci ; 21(21)2020 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-33142884

RESUMEN

Redox reactions are of high fundamental and practical interest since they are involved in both normal physiology and the pathogenesis of various diseases. However, this area of research has always been a relatively problematic field in the context of analytical approaches, mostly because of the unstable nature of the compounds that are measured. Genetically encoded sensors allow for the registration of highly reactive molecules in real-time mode and, therefore, they began a new era in redox biology. Their strongest points manifest most brightly in in vivo experiments and pave the way for the non-invasive investigation of biochemical pathways that proceed in organisms from different systematic groups. In the first part of the review, we briefly describe the redox sensors that were used in vivo as well as summarize the model systems to which they were applied. Next, we thoroughly discuss the biological results obtained in these studies in regard to animals, plants, as well as unicellular eukaryotes and prokaryotes. We hope that this work reflects the amazing power of this technology and can serve as a useful guide for biologists and chemists who work in the field of redox processes.


Asunto(s)
Técnicas Biosensibles/métodos , Proteínas Luminiscentes/genética , Imagen Molecular/métodos , Animales , Glutatión/metabolismo , Humanos , Proteínas Luminiscentes/metabolismo , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismo
10.
Int J Mol Sci ; 20(24)2019 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-31847129

RESUMEN

4-methylumbelliferone (4MU) is an inhibitor of hyaluronan deposition and an active substance of hymecromone, a choleretic and antispasmodic drug. 4MU reported to be anti-fibrotic in mouse models; however, precise mechanism of action still requires further investigation. Here we describe the cellular and molecular mechanisms of 4MU action on CCl4-induced liver fibrosis in mice using NGS transcriptome, Q-PCR and immunohistochemical analysis. Collagen and hyaluronan deposition were prevented by 4MU. The CCl4 stimulated expression of Col1a and αSMA were reduced, while the expression of the ECM catabolic gene Hyal1 was increased in the presence of 4MU. Bioinformatic analysis identified an activation of TGF-beta and Wnt/beta-catenin signaling pathways, and inhibition of the genes associated with lipid metabolism by CCL4 treatment, while 4MU restored key markers of these pathways to the control level. Immunohistochemical analysis reveals the suppression of hepatic stellate cells (HSCs) transdifferentiation to myofibroblasts by 4MU treatment. The drug affected the localization of HSCs and macrophages in the sites of fibrogenesis. CCl4 treatment induced the expression of FSTL1, which was downregulated by 4MU. Our results support the hypothesis that 4MU alleviates CCl4-induced liver fibrosis by reducing hyaluronan deposition and downregulating FSTL1 expression, accompanied by the suppression of HSC trans-differentiation and altered macrophage localization.


Asunto(s)
Proteínas Relacionadas con la Folistatina/biosíntesis , Regulación de la Expresión Génica/efectos de los fármacos , Ácido Hialurónico/biosíntesis , Himecromona/farmacología , Cirrosis Hepática , Vía de Señalización Wnt/efectos de los fármacos , Actinas/biosíntesis , Animales , Intoxicación por Tetracloruro de Carbono/metabolismo , Intoxicación por Tetracloruro de Carbono/patología , Intoxicación por Tetracloruro de Carbono/prevención & control , Transdiferenciación Celular/efectos de los fármacos , Femenino , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Hialuronoglucosaminidasa/biosíntesis , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Cirrosis Hepática/prevención & control , Ratones , Ratones Endogámicos BALB C , Miofibroblastos/metabolismo , Miofibroblastos/patología
11.
Inorg Chem ; 57(3): 1184-1195, 2018 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-29356517

RESUMEN

The structures of several fluoroscandate compounds are presented here using a characterization approach combining powder X-ray diffraction and solid-state NMR. The structure of K5Sc3F14 was fully determined from Rietveld refinement performed on powder X-ray diffraction data. Moreover, the local structures of NaScF4, Li3ScF6, KSc2F7, and Na3ScF6 compounds were studied in detail from solid-state 19F and 45Sc NMR experiments. The 45Sc chemical shift ranges for six- and seven-coordinated scandium environments were defined. The 19F chemical shift ranges for bridging and terminal fluorine atoms were also determined. First-principles calculations of the 19F and 45Sc NMR parameters were carried out using plane-wave basis sets and periodic boundary conditions (CASTEP), and the results were compared with the experimental data. A good agreement between the calculated shielding constants and experimental chemical shifts was obtained. This demonstrates the good potential of computational methods in spectroscopic assignments of solid-state 45Sc NMR spectroscopy.

12.
Methods Mol Biol ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38967913

RESUMEN

The ability to alternate between quiescent and proliferating states is a remarkable feature of many types of somatic stem cells. The balance between quiescent and proliferating states is vital for maintenance of stem cells over the lifespan, and its disturbance may lead to premature depletion of the stem cell pool and loss of the tissue regenerative or renewal capacity at later stages of life. The question on how this balance is regulated is of critical importance in stem cell research and biology of aging. Assessment of the balance between quiescent and proliferating states has remained challenged until recently due to the lack of approaches for robust determination of the rate at which stem cells exit reversible cell cycle arrest. Here, we propose a simple method for detection of those stem cells that have entered the division cycle after a prolonged period of quiescence.The method combines cumulative and pulse labeling with thymidine analogues 5-bromo-2'-deoxyuridine (BrdU) and 5-ethynyl-2'-deoxyuridine (EdU). In the discussed labeling scheme, cells that have incorporated only the second label, EdU, are de novo dividing cells. The suggested double labeling method provides quantitative assessment of the rate at which stem cells exit the quiescent state and allows the fates of de novo dividing stem cells to be traced.

13.
J Phys Chem B ; 128(16): 3972-3980, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38624173

RESUMEN

Complex molten chloride salt mixtures of uranium, magnesium, and sodium are top candidates for promising nuclear energy technologies to produce electricity based on molten salt reactors. From a local structural perspective, LaCl3 is similar to UCl3 and hence a good proxy to study these complex salt mixtures. As fission products, lanthanide salts and their mixtures are also very important in their own right. This article describes from an experimental and theory perspective how very different the structural roles of MgCl2 and NaCl are in mixtures with LaCl3. We find that, whereas MgCl2 becomes an integral part of multivalent ionic networks, NaCl separates them. In a recent article (J. Am. Chem. Soc. 2022, 144, 21751-21762) we have called the disruptive behavior of NaCl "the spacer salt effect". Because of the heterogeneous nature of these salt mixtures, there are multiple structural motifs in the melt, each with its particular free energetics. Our work identifies and quantifies these; it also elucidates the mechanisms through which Cl- ions exchange between Mg2+-rich and La3+-rich environments.

14.
Prog Neurobiol ; 235: 102600, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38548126

RESUMEN

Animal models of human neurological disorders provide valuable experimental tools which enable us to study various aspects of disorder pathogeneses, ranging from structural abnormalities and disrupted metabolism and signaling to motor and mental deficits, and allow us to test novel therapies in preclinical studies. To be valid, these animal models should recapitulate complex pathological features at the molecular, cellular, tissue, and behavioral levels as closely as possible to those observed in human subjects. Pathological states resembling known human neurological disorders can be induced in animal species by toxins, genetic factors, lesioning, or exposure to extreme conditions. In recent years, novel animal models recapitulating neuropathologies in humans have been introduced. These animal models are based on synthetic biology approaches: opto- and chemogenetics. In this paper, we review recent opto- and chemogenetics-based animal models of human neurological disorders. These models allow for the creation of pathological states by disrupting specific processes at the cellular level. The artificial pathological states mimic a range of human neurological disorders, such as aging-related dementia, Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, epilepsy, and ataxias. Opto- and chemogenetics provide new opportunities unavailable with other animal models of human neurological disorders. These techniques enable researchers to induce neuropathological states varying in severity and ranging from acute to chronic. We also discuss future directions for the development and application of synthetic biology approaches for modeling neurological disorders.


Asunto(s)
Epilepsia , Enfermedad de Parkinson , Animales , Humanos , Optogenética/métodos , Modelos Animales , Neuropatología
15.
Hum Genome Var ; 11(1): 26, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39013858

RESUMEN

Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive eye disease. GDLD is characterized by the loss of barrier function in corneal epithelial cells (CECs) and amyloid deposition due to pathogenic variants in the TACSTD2 gene. Limbal stem cell transplantation (LSCT) has been suggested as an effective therapeutic alternative for patients with GDLD. However, despite LSCT, amyloid deposition recurs in some patients. The pathogenesis of recurrence is poorly studied. We present the case of a patient with GDLD. Genetic analysis revealed a homozygous deletion, NM_002353.3:c.653del, in the TACSTD2 gene. Functional analysis in a cell model system revealed the loss of the transmembrane domain and subcellular protein mislocalization. The patient with GDLD underwent direct allogeneic LSCT with epithelial debridement followed by deep anterior lamellar keratoplasty 10 months later due to amyloid deposition and deterioration of vision. Taken together, the results of transcriptome analysis and immunofluorescence staining of post-LSCT corneal sample with amyloid deposits obtained during keratoplasty demonstrated complete restoration of wild-type TACSTD2 expression, indicating that donor CECs replaced host CECs. Our study provides experimental evidence that amyloid deposition can recur after LSCT despite complete restoration of wild-type TACSTD2 expression.

16.
Mol Neurobiol ; 2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-37995077

RESUMEN

A delicate balance between quiescence and division of the radial glia-like stem cells (RGLs) ensures continuation of adult hippocampal neurogenesis (AHN) over the lifespan. Transient or persistent perturbations of this balance due to a brain pathology, drug administration, or therapy can lead to unfavorable long-term outcomes such as premature depletion of the RGLs, decreased AHN, and cognitive deficit. Memantine, a drug used for alleviating the symptoms of Alzheimer's disease, and electroconvulsive seizure (ECS), a procedure used for treating drug-resistant major depression or bipolar disorder, are known strong AHN inducers; they were earlier demonstrated to increase numbers of dividing RGLs. Here, we demonstrated that 1-month stimulation of quiescent RGLs by either memantine or ECS leads to premature exhaustion of their pool and altered AHN at later stages of life and that aging of the brain modulates the ability of the quiescent RGLs to be recruited into the cell cycle by these AHN inducers. Our findings support the aging-related divergence of functional features of quiescent RGLs and have a number of implications for the practical assessment of drugs and treatments with respect to their action on quiescent RGLs at different stages of life in animal preclinical studies.

17.
ACS Appl Mater Interfaces ; 15(10): 13772-13782, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36877214

RESUMEN

Understanding the mechanisms leading to the degradation of alloys in molten salts at elevated temperatures is significant for developing several key energy generation and storage technologies, including concentrated solar and next-generation nuclear power plants. Specifically, the fundamental mechanisms of different types of corrosion leading to various morphological evolution characteristics for changing reaction conditions between the molten salt and alloy remain unclear. In this work, the three-dimensional (3D) morphological evolution of Ni-20Cr in KCl-MgCl2 is studied at 600 °C by combining in situ synchrotron X-ray and electron microscopy techniques. By further comparing different morphology evolution characteristics in the temperature range of 500-800 °C, the relative rates between diffusion and reaction at the salt-metal interface lead to different morphological evolution pathways, including intergranular corrosion and percolation dealloying. In this work, the temperature-dependent mechanisms of the interactions between metals and molten salts are discussed, providing insights for predicting molten salt corrosion in real-world applications.

18.
Redox Biol ; 60: 102604, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36640726

RESUMEN

Oxidative stress, a state of disrupted redox signaling, reactive oxygen species (ROS) overproduction, and oxidative cell damage, accompanies numerous brain pathologies, including aging-related dementia and Alzheimer's disease, the most common neurodegenerative disorder of the elderly population. However, a causative role of neuronal oxidative stress in the development of aging-related cognitive decline and neurodegeneration remains elusive because of the lack of approaches for modeling isolated oxidative injury in the brain. Here, we present a chemogenetic approach based on the yeast flavoprotein d-amino acid oxidase (DAAO) for the generation of intraneuronal hydrogen peroxide (H2O2). To validate this chemogenetic tool, DAAO and HyPer7, an ultrasensitive genetically encoded H2O2 biosensor, were targeted to neurons. Changes in the fluorescence of HyPer7 upon treatment of neurons expressing DAAO with d-norvaline (D-Nva), a DAAO substrate, confirmed chemogenetically induced production of intraneuornal H2O2. Then, using the verified chemogenetic tool, we emulated isolated intraneuronal oxidative stress in acute brain slices and, using electrophysiological recordings, revealed that it does not alter basal synaptic transmission and the probability of neurotransmitter release from presynaptic terminals but reduces long-term potentiation (LTP). Moreover, treating neurons expressing DAAO with D-Nva via the patch pipette also decreases LTP. This observation indicates that isolated oxidative stress affects synaptic plasticity at single cell level. Our results broaden the toolset for studying normal redox regulation in the brain and elucidating the role of oxidative stress to the pathogenesis of cognitive aging and the early stages of aging-related neurodegenerative diseases. The proposed approach is useful for identification of early markers of neuronal oxidative stress and may be used in screens of potential antioxidants effective against neuronal oxidative injury.


Asunto(s)
Peróxido de Hidrógeno , Estrés Oxidativo , Humanos , Anciano , Peróxido de Hidrógeno/farmacología , Especies Reactivas de Oxígeno/farmacología , Antioxidantes/farmacología , Plasticidad Neuronal/fisiología
19.
Virusdisease ; 33(2): 155-165, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35991701

RESUMEN

The purpose of this study is to diagnose herpesvirus infections in refractory atypical trigeminal neuralgia, to assess pathogenetic links, and to explore the efficacy of antiviral treatment. In a prospective controlled study, 95 patients with trigeminal neuralgia received antiviral therapy (valacyclovir + alpha2b-interferon) (experimental group, EG). Other patients refused to receive treatment (control group 1 (CG1), n = 31). Control group 2 (CG2) included 32 healthy individuals of the same age and sex. Herpesvirus infection was diagnosed in blood leukocytes by PCR (Biocom, Russian Federation). Serum concentrations of IgM, IgA and IgG to HSV-1/2, VZV (ELISA, Vector-Best, Russian Federation) were determined. Reactivation of herpesvirus infections was observed in the EG in 87% of cases. The heterogeneity of herpesvirus-associated damage of trigeminal nerves and anatomically related areas of the central nervous system (CNS) has been demonstrated. The treatment applied was effective for herpesvirus infection (77%) and pain (61%) and ineffective for immunity correction (26% of cases). Atypical refractory trigeminal neuralgia is associated with herpesvirus infections that reactivate due to minor immunodeficiencies. Antiviral treatment suppresses herpesviruses and reduces the intensity of pain. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-022-00769-9.

20.
J Phys Chem Lett ; 13(25): 5956-5962, 2022 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-35735362

RESUMEN

Molten inorganic salts are attracting resurgent attention because of their unique physicochemical properties, making them promising media for next-generation concentrating solar power systems and molten salt reactors. The dynamics of these highly disordered ionic media is largely studied by theoretical simulations, while the robust experimental techniques capable of observing local dynamics are not well-developed. To provide fundamental insights into the atomic-scale transport properties of molten salts, we report the real-space dynamics of molten magnesium chloride at high temperatures employing the Van Hove correlation function obtained by inelastic neutron scattering. Our results directly depict the distance-dependent dynamics of a molten salt on the picosecond time scale. This study demonstrates the capability of the developed approach to describe the locally correlated- and self-dynamics in molten salts, significantly improving our understanding of the interplay between microscopic structural parameters and their dynamics that ultimately control physical properties of condensed matter in extreme environments.

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