RESUMO
The properties of kagome metals are governed by the interdependence of band topology and electronic correlations resulting in remarkably rich phase diagrams. Here, we study the temperature evolution of the bulk electronic structure of the antiferromagnetic kagome metal FeGe using infrared spectroscopy. We uncover drastic changes in the low-energy interband absorption at the 100 K structural phase transition that has been linked to a charge-density-wave (CDW) instability. We explain this effect by the minuscule Fe displacement in the kagome plane, which results in parallel bands in the vicinity of the Fermi level. In contrast to conventional CDW materials, however, the spectral weight shifts to low energies, ruling out the opening of a CDW gap in FeGe.
RESUMO
As a natural mutation of the human ccr5 gene has been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, a new avenue has opened in the development of alternative treatment approaches through genome editing. One of the two chemokine co-receptors of the plasma membrane is utilized by HIV-1 to infect CD4+ cells. HIV-1 strains that utilize CCR5 circulate in early infection, and strains that utilize CXCR4 circulate at advanced stages. A complex relationship may exist in the expression regulation of the receptors and may affect virus replication in cells that normally do not express CCR5 on the membrane, such as the MT-4 cell line. MT-4 cells were used to study the effect of ccr5 modification HIV-1 replication in vitro. Genetic modification of ccr5 in MT-4 cells was shown to increase the activities of HIV-1 strains, especially in homozygote. The results indicate that genome editing should be performed with caution in human cells and that the issue needs comprehensive investigation.
Assuntos
Infecções por HIV , HIV-1 , Receptores CCR5 , Humanos , Linfócitos T CD4-Positivos , Linhagem Celular , Células Cultivadas , Infecções por HIV/genética , HIV-1/genética , HIV-1/metabolismo , Receptores CCR5/genéticaRESUMO
INTRODUCTION: A vaccine against hepatitis C has not yet been developed. Recombinant proteins and plasmids encoding hepatitis C virus (HCV) proteins, the components of candidate vaccines, induce a weak immune response and require the use of adjuvants. The aim of the work was to study the adjuvant action of an aqueous solution of fullerene C60 during immunization of mice with HCV recombinant protein NS5B (rNS5B) that is an RNA-dependent RNA polymerase, or with NS5B-encoding pcNS5B plasmid. MATERIALS AND METHODS: An aqueous solution of dispersed fullerene (dnC60) was obtained by ultrafiltration. C57BL/6 mice were immunized with rNS5B subcutaneously, pcNS5B intramuscularly mixed with different doses of dnC60 three times, then the humoral and cellular response to HCV was evaluated. RESULTS: Mice immunization with rNS5B in a mixture with dnC60 at doses of 250 g/mouse significantly induced humoral response: a dose-dependent increase in IgG1 antibody titers was 720 times higher than in the absence of fullerene. There was no increase in the cellular response to rNS5B when administered with dnC60. The humoral response to DNA immunization was weak in mice of all groups receiving pcNS5B. The cellular response was suppressed when the plasmid was injected in a mixture with dnC60. CONCLUSIONS: Dispersed fullerene dnC60 is a promising adjuvant for increasing the immunostimulating activity of weakly immunogenic proteins including surface and other HCV proteins, important for a protective response. Further research is needed to enhance the ability of dnC60 to boost the cellular immune response to the components of the candidate vaccine.
Assuntos
Fulerenos , Hepatite C , Vacinas de DNA , Vacinas contra Hepatite Viral , Camundongos , Animais , Hepacivirus , Fulerenos/farmacologia , Fulerenos/metabolismo , Sequência de Bases , Aminoácidos/genética , Aminoácidos/metabolismo , Aminoácidos/farmacologia , Camundongos Endogâmicos C57BL , Adjuvantes Imunológicos/genética , Imunidade Celular , Proteínas Recombinantes/genética , Camundongos Endogâmicos BALB C , Vacinas de DNA/genética , Vacinas de DNA/farmacologia , Vacinas contra Hepatite Viral/genética , Vacinas contra Hepatite Viral/farmacologiaRESUMO
The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012-2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy) carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 µM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility - high activity (IC50 = 1.06 µg/mL) and high selectivity index (SI = 78.6) - this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.
RESUMO
Lithium salts have been the mainstay of treatment for bipolar disorder for more than 50 years, since the FDA approved the treatment in 1970. Molecular mechanisms of lithium's action include inhibition of glycogen synthase kinase 3 beta and inositol monophosphatase, resulting in induction of brain-derived neurotrophic factor, antiapoptotic proteins, deprivation of calcium-induced apoptosis. Recent findings suggest autophagy regulation as a possible mechanism of lithium neuroprotective action. Moreover, lithium treatment has been reported to decrease accumulation of various pathological proteins including phosphorylated tau and amyloid-B. Also, telomeres length and telomerase activity are suggested to be upregulated by lithium. Clinical applications of lithium treatment include various neurodegenerative diseases, primarily Alzheimer disease, with increasing importance given to the use of lithium microdoses. Chemoreactome screening is used to find more safe and effective lithium compounds.
Assuntos
Transtorno Bipolar , Doenças Neurodegenerativas , Humanos , Lítio/farmacologia , Lítio/uso terapêutico , Compostos de Lítio/farmacologia , Compostos de Lítio/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , NeuroproteçãoRESUMO
Landau-level spectroscopy, the optical analysis of electrons in materials subject to a strong magnetic field, is a versatile probe of the electronic band structure and has been successfully used in the identification of novel states of matter such as Dirac electrons, topological materials or Weyl semimetals. The latter arise from a complex interplay between crystal symmetry, spin-orbit interaction, and inverse ordering of electronic bands. Here, we report on unusual Landau-level transitions in the monopnictide TaP that decrease in energy with increasing magnetic field. We show that these transitions arise naturally at intermediate energies in time-reversal-invariant Weyl semimetals where the Weyl nodes are formed by a partially gapped nodal-loop in the band structure. We propose a simple theoretical model for electronic bands in these Weyl materials that captures the collected magneto-optical data to great extent.
RESUMO
Dose-dependent protective effects of lanthanum nitrate solution and gel were shown on the model of experimental infection caused by a virulent strain of Shigella flexneri 2a or opportunistic bacteria Klebsiella pneumoniae in outbred and DBA mice.
Assuntos
Lantânio/farmacologia , Animais , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Camundongos , Camundongos Endogâmicos DBA , Shigella flexneri/efeitos dos fármacos , Shigella flexneri/patogenicidade , Simplexvirus/efeitos dos fármacos , Simplexvirus/patogenicidadeRESUMO
We measured the optical reflectivity of the Dirac material Au2Pb in a broad frequency range (30-48 000 cm-1) for temperatures between 9 and 300 K. The optical conductivity, computed from the reflectivity, is dominated by free-carrier contributions from topologically trivial bulk bands at all temperatures. The temperature-independent total plasma frequency of these carriers is [Formula: see text] eV. Overall, optical response of Au2Pb is typically metallic with no signs of localization and bad-metal behavior.
RESUMO
The search for new adjuvants remains the critical task for the creation of hepatitis C vaccines due to the weak immunogenicity of biotechnological products. When immunizing mice with the recombinant proteins NS3 and NS5B of the hepatitis C virus (HCV), the adjuvant activity of three immunomodulators was compared. Phosprenyl® on the basis of polyprenyl phosphate (PPP), chemically synthesized analogue of the bacterial cell wall glucosaminyl muramyl dipeptide (GMDP), and IFN-α recombinant protein were tested. GMDP increased the activity of IgG1 antibodies 4-6 times but did not stimulate the production of IFN-γ; IFN-α has not shown any adjuvant properties. The introduction of recombinant HCV proteins together with PPP in low doses increased the activity of IgG2a isotype antibodies 4-7 times and increased IFN-γ secretion 3 times. Thus, it was first shown that PPP polarizes the immune response to Th1-type and is a promising adjuvant for the development of a vaccine against hepatitis C.
Assuntos
Adjuvantes Imunológicos , Hepacivirus/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Fosfatos de Poli-Isoprenil/farmacologia , Vacinas/uso terapêutico , Animais , Imunoglobulina G/metabolismo , Fatores Imunológicos/classificação , Fatores Imunológicos/farmacologia , Camundongos , Proteínas Recombinantes , Replicação ViralRESUMO
The complex optical conductivity of the half-Heusler compound GdPtBi is measured in a frequency range from 20 to 22 000 cm^{-1} (2.5 meV-2.73 eV) at temperatures down to 10 K in zero magnetic field. We find the real part of the conductivity, σ_{1}(ω), to be almost perfectly linear in frequency over a broad range from 50 to 800 cm^{-1} (â¼6-100 meV) for T≤50 K. This linearity strongly suggests the presence of three-dimensional linear electronic bands with band crossings (nodes) near the chemical potential. Band-structure calculations show the presence of triple points, where one doubly degenerate and one nondegenerate band cross each other in close vicinity of the chemical potential. From a comparison of our data with the optical conductivity computed from the band structure, we conclude that the observed nearly linear σ_{1}(ω) originates as a cumulative effect from all the transitions near the triple points.
RESUMO
ZrSiS exhibits a frequency-independent interband conductivity σ(ω)=const(ω)≡σ_{flat} in a broad range from 250 to 2500 cm^{-1} (30-300 meV). This makes ZrSiS similar to (quasi-)two-dimensional Dirac electron systems, such as graphite and graphene. We assign the flat optical conductivity to the transitions between quasi-two-dimensional Dirac bands near the Fermi level. In contrast to graphene, σ_{flat} is not universal but related to the length of the nodal line in the reciprocal space, k_{0}. Because of spin-orbit coupling, the discussed Dirac bands in ZrSiS possess a small gap Δ, for which we determine an upper bound max(Δ)=30 meV from our optical measurements. At low temperatures the momentum-relaxation rate collapses, and the characteristic length scale of momentum relaxation is of the order of microns below 50 K.
RESUMO
Zinc and vitamin C supplementation of the body is important for CNS functioning. Zinc ions are involved in the neurotransmission (signal transmission from acetylcholine, catecholamine, serotonin, prostaglandin receptors) and in ubiquitin-related protein degradation. Zinc deficits are associated with Alzheimer's disease and depression. Zinc supplementation (10-30 mg daily) improves neurologic recovery rate in patients with stroke and brain injury, has a positive impact on memory and reduces hyperactivity in children. Vitamin C, a zinc synergist, maintains antioxidant resources of the brain, synaptic activity and detoxification. Vitamin C in dose 130-500 mg daily should be used to prevent dementia and neurodegenerative pathology.
Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Atenção/efeitos dos fármacos , Memória/efeitos dos fármacos , Doenças do Sistema Nervoso/prevenção & controle , Vitaminas/administração & dosagem , Zinco/farmacologia , Doença de Alzheimer/prevenção & controle , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Criança , Suplementos Nutricionais , Sinergismo Farmacológico , Humanos , Doenças do Sistema Nervoso/epidemiologia , Proteólise , Risco , Ubiquitinação , Vitaminas/farmacologia , Zinco/administração & dosagem , Zinco/deficiênciaRESUMO
Effects of Miramistin and Phosprenil on biofilms of S. pyogenes, S. aureus, E. coli, L. acidophilus, and L. plantarum were studied. Significant differences in the effects of these substances on mature biofilms of microorganisms and the process of their formation were observed. Miramistin had significant inhibiting effects on the forming of biofilms and on the formed biofilms of all studied microorganisms. Treatment with Miramistin inhibited biofilm formation by 2-3 times compared to the control. This effect was found already after using of Miramistin in the low doses (3.12 µg/ml). Inhibition of the growth of a formed biofilm was observed only after treatment with Miramistin in the high doses (25-50 µg/ml). Phosprenil in the high doses (15-30 mg/ml) inhibited the forming of biofilms, especially the biofilms of S. pyogenes and L. plantarum (by 3-4.5 times). Treatment of formed biofilms with the agent in doses of 6.0 and 0.6 mg/ml was associated with pronounced stimulation of its growth in S. pyogenes, S. aureus, and L. acidophilus.
Assuntos
Antibacterianos/farmacologia , Compostos de Benzalcônio/farmacologia , Biofilmes/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacosRESUMO
AIM: To study a neuroprotective effect of mexidol on the cell model of glutamate stress. MATERIAL AND METHODS: Cytological studies of an effect of glutamate stress on cerebellar granule cells were carried out. RESULTS: Mexidol increased neuronal survival after the addition of glutamate by 8-10% (p<0.05). The effect of mexidol was more pronounced at the stage of neuron culture growth (5 days), cell survivability increased on average by 20%. CONCLUSION: The results of the study confirmed the neuroprotective effect of mexidol in the neuronal culture in glutamate toxicity model.
Assuntos
Antioxidantes/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Picolinas/farmacologia , Animais , Sobrevivência Celular , Células Cultivadas , Cerebelo/citologia , Cerebelo/efeitos dos fármacos , Ácido Glutâmico/toxicidade , Modelos Biológicos , RatosRESUMO
The antiviral activity of Phosprenyl and Gamapren in vitro against highly pathogenic strain of avian influenza H5N1 virus was studied. Inoculation of the virus to the susceptible cell culture led to development of the cytopathogenic effect. Preliminary introduction of Phosprenyl and Gamapren an hour prior to infecting the cells with virus 10.0 TCID50 dose completely inhibited the cytopathogenic activity of the virus. At higher doses of virus (100.0 TCID50) significant inhibition of the infectious activity of the virus was observed: 70% of infected cells survived under the action of Phosprenyl, and 90% under the action of Gamapren. With the introduction of the preparations simultaneously with the infection of cells with virus at a dose of 10.0 TCID50 virtually 100% of infected cells survived, while in control cultures death of 100% of the cells occurred. After infection with the virus at a dose of 100.0 TCID50 Phosprenyl and Gamapren caused 50% protection of the cells. The antiviral effect of the drugs Phosprenyl and Gamapren may be associated not only with their virulicidal, but with anti-viral activity as well.
Assuntos
Antivirais/farmacologia , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Fosfatos de Poli-Isoprenil/farmacologia , Animais , HumanosRESUMO
For over 60 years, high doses of lithium (hundreds of milligrams of elemental lithium) have being used to treat bipolar disorder. However, only during the past 20 years the relevant basic and clinical studies have shown that neuroprotective and neurotrophic effects of lithium are possible in much smaller doses ( hundreds of micrograms of elemental lithium). These data indicate a significant potential for the clinical applications of lithium-based drugs in modern neurology for the purposes of prevention and treatment of neurodegenerative and ischemic pathologies. Pharmacological and molecular biology studies indicated that the inhibition of glycogen synthase kinase-syntentase-3 (GSK-3) and induction of brain-derived neurotrophic factors are the main mechanisms of neurotropic actions of lithium. Also, by inhibiting the NMDA receptors, lithium regulates the calcium homeostasis and inhibits the activation of calcium-dependent apotosis. These and other molecular mechanisms of lithium action protect neurons from ischemia and neurodegeneration thus contributing to a significant reduction of neurological deficit in various models of stroke and neurodegenerative diseases.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Compostos de Lítio/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Humanos , Compostos de Lítio/farmacologia , Receptores de N-Metil-D-AspartatoRESUMO
AIM: To investigate the effect of cerebrolysin on the growth and metastasis of malignant tumors in mice (a model of lung carcinoma Lewis). MATERIAL AND METHODS: The study was performed on 60 male mice, hybrids F1 (the age of 2-2.5 months, body weight 19-22g.). Transplantable epidermoid Lewis lung carcinoma (LLC) was used as a standard experimental model to evaluate the properties of the potential antitumor agents. Experimental animals were administered a single intraperitoneal injection of cerebrolysin in doses of 524 mg/kg (n=20) and 1800 mg/kg (n=20) daily from 2 to 16 days after tumor transplantation. RESULTS AND CONCLUSION: Compared with the control group (n=20), cerebrolysin induced growth inhibition of LLC during the treatment (7 to 16 days). An impact of the drug was accompanied by the inhibition of the tumor growth rate by 10-15% (p<0.05). Cerebrolysin demonstrated a dose-dependent effect of reducing the large number of metastases: a number of large metastases significantly decreased by 30-50% with the increase of cerebrolysin dose (p=0.01). Cerebrolysin can significantly suppress the growth rate of Lewis lung carcinoma.
Assuntos
Aminoácidos/farmacologia , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVE: Investigation of the neuroprotective properties of lithium ascorbate on the stress models in vivo and in vitro. MATERIAL AND METHODS: Neurocytological and behavioral studies on nerve cell culture and animal stress models. RESULTS: Significant neuroprotective effect of lithium ascorbate in neuronal cultures exposed to glutamate toxicity and adaptogenic effect of this drug in stress model in rats were shown. CONCLUSION: The results suggest lithium ascorbate has a high neuroprotective potential in stress models in vivo and in vitro.
Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Compostos de Lítio/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Animais , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Células Cultivadas , Modelos Animais de Doenças , Ácido Glutâmico/farmacologia , Compostos de Lítio/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos WistarRESUMO
An experimental model of the primary genital herpes (herpes simplex type 2, HSV-2) in the female guinea pigs was suggested to study the infectious process activity of polyprenyl phosphates (PPP) and PPP+acyclovir (AC) complex treatment. The morphofunctional features of the guinea pig ovaries were studied in the control and experimental groups (the latter were inoculated with PPP and/or AC as a primary infection treatment) at the stage of the recurrent genital herpes aggravation. It was shown that in the case of combined PPP +AC use significant changes in the disease symptoms were observed, as well as a decrease in the infectious process activity and duration, and positive remote effect on the ovarian morphophysiology.
Assuntos
Aciclovir/farmacologia , Antivirais/farmacologia , Herpes Genital/tratamento farmacológico , Herpesvirus Humano 2/metabolismo , Fosfatos de Poli-Isoprenil/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Cobaias , Herpes Genital/metabolismo , HumanosRESUMO
Generalized results of 15-year prospective studies of frequency of occurrence and dynamics of circulation of pathogenetically significant LPS/O-antigens, high molecular weight proteins, including CagA, and VacA of Helicobacter pylori in biological media of organism in patients with gastrointestinal diseases and asymptomatic volunteers due to effects of external and internal factors are presented. Features of antigen circulation and reciprocal immune reaction of the organism are established, that reflect their interaction in the parasite-host tandem, risk and prognosis of possible complications in the process of long-term persistence of Helicobacter pylori in the organism.