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1.
J Biol Regul Homeost Agents ; 35(2 Suppl. 1): 323-329, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34281328

RESUMO

The aim of this study was to compare the size and shape of bone fragments produced by the ultrasonic and drilling procedures in implant site preparation. Six pieces of rib selected as experimental animal model of 15 cm in length and at least 13 mm of thickness were used. The samples were treated and divided into 2 groups as follows: group A (GA) ultrasonic implant site preparation technique; group B (GB) traditional surgical drill technique. Ultrasonic implant site preparation (GA) was carried out using a sequence of progressive diameter (1.00 mm, 2.00 mm and 3.00 mm) conical inserts at a depth of 10 mm. Standard drill implant site procedure (GB) was carried out with a sequence of 1.00 mm, 2.00 mm, and 3.00 mm cylindrical twist drills, for preparing an implant site at a depth of 10 mm. From each group bone fragments (0.1 gr) were collected from both cortical and cancellous bone preparation and their dimensions were evaluated by optic microscope analysis. The bone debris dimensions procured by cortical bone of Group A and Group B were, respectively, 0.14×0.16 mm (±0.13) and 1.15 ×0.92 mm (±0.68). The bone debris dimensions procured by cancellous bone of Group A and Group B were, respectively, 0.15×0.10 mm (±0.10) and 1.98×1.27 mm (±0.94). Ultrasonic implant site preparation technique was able to micronize bone and to remove all debris with cooling system. Surgical drills tend to fracture bone, creating a weaker structure and fragments of larger size, which remain in considerable quantity over bone walls during site preparation. Within the limits of the present study, the ultrasonic implant preparation was able to produce reduced bone sediments and a clear bed implant favoring osseointegration.


Assuntos
Osteotomia , Ultrassom , Animais , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/cirurgia , Bovinos , Modelos Animais , Osseointegração
2.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198694

RESUMO

Plasmonic nanoparticles are increasingly employed in several fields, thanks to their unique, promising properties. In particular, these particles exhibit a surface plasmon resonance combined with outstanding absorption and scattering properties. They are also easy to synthesize and functionalize, making them ideal for nanotechnology applications. However, the physicochemical properties of these nanoparticles can make them potentially toxic, even if their bulk metallic forms are almost inert. In this review, we aim to provide a more comprehensive understanding of the potential adverse effects of plasmonic nanoparticles in zebrafish (Danio rerio) during both development and adulthood, focusing our attention on the most common materials used, i.e., gold and silver.


Assuntos
Modelos Animais , Nanopartículas/toxicidade , Testes de Toxicidade , Animais , Tamanho da Partícula , Peixe-Zebra
3.
Nutrients ; 13(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205338

RESUMO

This study investigated the antioxidant effects of whey protein peptide on learning and memory in aging C57BL/6N mice. A total of 72 SPF male C57BL/6N mice were used. Twelve mice were randomly selected as the control group, and the other mice were intraperitoneally injected with D-galactose (100 mg/kg body weight for 6 weeks), during which, the mice in the control group were intraperitoneally injected with the same amount of normal saline. After 6 weeks, the blood was taken from the epicanthus and the serum MDA level was measured, according to which, the mice were randomly divided into the model control group, the whey protein group (1.5 g/kg body weight), and three Whey protein peptide (WHP) intervention groups (0.3 g/kg body weight, 1.5 g/kg body weight, 3.0 g/kg body weight). The water solution of the test sample was administered by oral gavage every day. The intervention period was 30 days, during which, the model control group, the whey protein group, and the whey protein peptide group continued receiving intraperitoneal injections of D-galactose, while the control group continued receiving intraperitoneal injections of normal saline. After the intervention, behavioral experiments were conducted in the following order: open field test, water maze test, and new object recognition test. After the behavioral experiment, the morphology of hippocampal formation was observed by HE staining and TUNEL labeling. Oxidative stress-related indexes in the serum, liver, and brain were detected. Expression levels of the cholinergic system-related enzymes and proinflammatory cytokines in brain tissue were detected. Western blot was used to detect the expression of synaptic plasticity-related proteins in the mouse brain. The results showed that WHP could significantly improve the accumulation of MDA and PC, increase the activities of SOD and GSH-Px, resist oxidative stress injury, and enhance the potential of endogenous antioxidant defense mechanisms. WHP can significantly improve the decline of aging-related spatial exploration, body movement, and spatial and non-spatial learning/memory ability. Its specific mechanism may be related to reducing the degeneration of hippocampal nerve cells, reducing the apoptosis of nerve cells, improving the activity of AChE, reducing the expression of inflammatory factors (TNF-α and IL-1ß) in brain tissue, reducing oxidative stress injury, and improving the expression of p-CaMKⅡ and BDNF synaptic plasticity protein. These results indicate that WHP can improve aging-related oxidative stress, as well as learning and memory impairment.


Assuntos
Envelhecimento/fisiologia , Antioxidantes/farmacologia , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Peptídeos/administração & dosagem , Proteínas do Soro do Leite/química , Envelhecimento/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Galactose/administração & dosagem , Hipocampo/citologia , Marcação In Situ das Extremidades Cortadas , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos
4.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206630

RESUMO

This Special Issue (SI), "Microgravity and Space Medicine", covers research articles and reviews focusing on gravitational biology, cancer research and space medicine [...].


Assuntos
Medicina Aeroespacial , Ausência de Peso , Medicina Aeroespacial/métodos , Animais , Humanos , Modelos Animais , Voo Espacial
5.
Transl Psychiatry ; 11(1): 373, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226504

RESUMO

Bipolar disorders (BDs) exhibit high heritability and symptoms typically first occur during late adolescence or early adulthood. Affected individuals may experience alternating bouts of mania/hypomania and depression, with euthymic periods of varying lengths interspersed between these extremes of mood. Clinical research studies have consistently demonstrated that BD patients have disturbances in circadian and seasonal rhythms, even when they are free of symptoms. In addition, some BD patients display seasonal patterns in the occurrence of manic/hypomanic and depressive episodes as well as the time of year when symptoms initially occur. Finally, the age of onset of BD symptoms is strongly influenced by the distance one lives from the equator. With few exceptions, animal models useful in the study of BD have not capitalized on these clinical findings regarding seasonal patterns in BD to explore molecular mechanisms associated with the expression of mania- and depression-like behaviors in laboratory animals. In particular, animal models would be especially useful in studying how rates of change in photoperiod that occur during early spring and fall interact with risk genes to increase the occurrence of mania- and depression-like phenotypes, respectively. Another unanswered question relates to the ways in which seasonally relevant changes in photoperiod affect responses to acute and chronic stressors in animal models. Going forward, we suggest ways in which translational research with animal models of BD could be strengthened through carefully controlled manipulations of photoperiod to enhance our understanding of mechanisms underlying seasonal patterns of BD symptoms in humans. In addition, we emphasize the value of incorporating diurnal rodent species as more appropriate animal models to study the effects of seasonal changes in light on symptoms of depression and mania that are characteristic of BD in humans.


Assuntos
Transtorno Bipolar , Adulto , Afeto , Animais , Humanos , Modelos Animais , Fotoperíodo , Estações do Ano
6.
Nat Commun ; 12(1): 4173, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234137

RESUMO

The integration of circadian and metabolic signals is essential for maintaining robust circadian rhythms and ensuring efficient metabolism and energy use. Using Drosophila as an animal model, we show that cellular protein O-GlcNAcylation exhibits robust 24-hour rhythm and represents a key post-translational mechanism that regulates circadian physiology. We observe strong correlation between protein O-GlcNAcylation rhythms and clock-controlled feeding-fasting cycles, suggesting that O-GlcNAcylation rhythms are primarily driven by nutrient input. Interestingly, daily O-GlcNAcylation rhythms are severely dampened when we subject flies to time-restricted feeding at unnatural feeding time. This suggests the presence of clock-regulated buffering mechanisms that prevent excessive O-GlcNAcylation at non-optimal times of the day-night cycle. We show that this buffering mechanism is mediated by the expression and activity of GFAT, OGT, and OGA, which are regulated through integration of circadian and metabolic signals. Finally, we generate a mathematical model to describe the key factors that regulate daily O-GlcNAcylation rhythm.


Assuntos
Ritmo Circadiano/genética , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/metabolismo , Hexosaminas/biossíntese , N-Acetilglucosaminiltransferases/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Acetilglucosamina/metabolismo , Animais , Animais Geneticamente Modificados , Vias Biossintéticas/genética , Relógios Circadianos/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Comportamento Alimentar/fisiologia , Feminino , Perfilação da Expressão Gênica , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/genética , Masculino , Modelos Animais , N-Acetilglucosaminiltransferases/genética , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo
7.
Nat Commun ; 12(1): 4409, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285209

RESUMO

Appetitive locomotion is essential for animals to approach rewards, such as food and prey. The neuronal circuitry controlling appetitive locomotion is unclear. In a goal-directed behavior-predatory hunting, we show an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to enhance appetitive locomotion in mice. This tectonigral pathway transmits locomotion-speed signals to dopamine neurons and triggers dopamine release in the dorsal striatum. Synaptic inactivation of this pathway impairs appetitive locomotion but not defensive locomotion. Conversely, activation of this pathway increases the speed and frequency of approach during predatory hunting, an effect that depends on the activities of SNc dopamine neurons. Together, these data reveal that the SC regulates locomotion-speed signals to SNc dopamine neurons to enhance appetitive locomotion in mice.


Assuntos
Comportamento Apetitivo/fisiologia , Locomoção/fisiologia , Parte Compacta da Substância Negra/fisiologia , Comportamento Predatório/fisiologia , Colículos Superiores/fisiologia , Animais , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Modelos Animais , Vias Neurais/fisiologia , Parte Compacta da Substância Negra/citologia , Técnicas Estereotáxicas , Colículos Superiores/citologia , Transmissão Sináptica/fisiologia
8.
Nat Commun ; 12(1): 4399, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285221

RESUMO

The decline of neuronal synapses is an established feature of ageing accompanied by the diminishment of neuronal function, and in the motor system at least, a reduction of behavioural capacity. Here, we have investigated Drosophila motor neuron synaptic terminals during ageing. We observed cumulative fragmentation of presynaptic structures accompanied by diminishment of both evoked and miniature neurotransmission occurring in tandem with reduced motor ability. Through discrete manipulation of each neurotransmission modality, we find that miniature but not evoked neurotransmission is required to maintain presynaptic architecture and that increasing miniature events can both preserve synaptic structures and prolong motor ability during ageing. Our results establish that miniature neurotransmission, formerly viewed as an epiphenomenon, is necessary for the long-term stability of synaptic connections.


Assuntos
Envelhecimento/fisiologia , Neurônios Motores/fisiologia , Terminações Pré-Sinápticas/fisiologia , Transmissão Sináptica/fisiologia , Animais , Animais Geneticamente Modificados , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Potencial Evocado Motor/fisiologia , Masculino , Microscopia Eletrônica , Modelos Animais , Neurônios Motores/ultraestrutura , Músculos/inervação , Músculos/fisiologia , Músculos/ultraestrutura , Terminações Pré-Sinápticas/ultraestrutura , Fatores de Tempo
9.
J Environ Sci (China) ; 105: 64-70, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34130840

RESUMO

Simulation of fine particulate matter (PM2.5) exposure is essential for evaluating adverse health effects. In this work, an ambient exposure system that mimicked real atmospheric conditions was installed in Taiyuan, China to study impacts of chronic PM2.5 exposure on adult and aged mice as well as Sirtuin3 knockout (Sirt3 KO) mice and wild-type (WT) mice. The real-ambient exposure system eliminated the possible artificial effects caused from exposure experiments and maintained the physiochemical characteristics of PM2.5. The case studies indicated that aged mice exhibited apparent heart dysfunction involving increased heart rate and decreased blood pressure after 17-week of real-ambient PM2.5 exposure. Meanwhile, 15-week of real-ambient PM2.5 exposure decreased the heart rate and amounts of associated catecholamines to induce heart failure in Sirt3 KO mice. Additionally, the increased pro-inflammatory cytokines and decreased platelet related indices suggested that inflammation occurred. The changes of biomarkers detected by targeted metabolomics confirmed metabolic disorder in WT and Sirt3 KO mice after exposed to real-ambient PM2.5. These results indicated that the real-ambient PM2.5 exposure system could evaluate the risks of certain diseases associated with air pollution and have great potential for supporting the investigations of PM2.5 effects on other types of rodent models.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Animais , China , Camundongos , Modelos Animais , Material Particulado/análise , Material Particulado/toxicidade
10.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071837

RESUMO

Phosphate homeostasis is essential for health and is achieved via interaction between the bone, kidney, small intestine, and parathyroid glands and via intricate processes involving phosphate transporters, phosphate sensors, and circulating hormones. Numerous genetic and acquired disorders are associated with disruption in these processes and can lead to significant morbidity and mortality. The role of the kidney in phosphate homeostasis is well known, although it is recognized that the cellular mechanisms in murine models and humans are different. Intestinal phosphate transport also appears to differ in humans and rodents, with recent studies demonstrating a dominant role for the paracellular pathway. The existence of phosphate sensing has been acknowledged for decades; however, the underlying molecular mechanisms are poorly understood. At least three phosphate sensors have emerged. PiT2 and FGFR1c both act as phosphate sensors controlling Fibroblast Growth Factor 23 secretion in bone, whereas the calcium-sensing receptor controls parathyroid hormone secretion in response to extracellular phosphate. All three of the proposed sensors are expressed in the kidney and intestine but their exact function in these organs is unknown. Understanding organ interactions and the mechanisms involved in phosphate sensing requires significant research to develop novel approaches for the treatment of phosphate homeostasis disorders.


Assuntos
Homeostase , Proteínas de Transporte de Fosfato/metabolismo , Fosfatos/metabolismo , Transdução de Sinais , Animais , Fenômenos Fisiológicos Celulares , Suscetibilidade a Doenças , Humanos , Modelos Animais , Especificidade de Órgãos
11.
Gene ; 794: 145752, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34082065

RESUMO

Intron retention (IR) is an important regulatory mechanism that affects gene expression and protein functions. Using klotho mice at the pre-symptomatic state, we discovered that retained-introns accumulated in several organs including the liver and that among these retained introns in the liver a subset was recovered to the normal state by a Japanese traditional herbal medicine. This is the first report of IR recovery by a medicine. IR-recovered genes fell into two categories: those involved in liver-specific metabolism and in splicing. Metabolome analysis of the liver showed that the klotho mice were under starvation stress. In addition, our differentially expressed gene analysis showed that liver metabolism was actually recovered by the herbal medicine at the transcriptional level. By analogy with the widespread accumulation of intron-retained pre-mRNAs induced by heat shock stress, we propose a model in which retained-introns in klotho mice were induced by an aging stress and in which this medicine-related IR recovery is indicative of the actual recovery of liver-specific metabolic function to the healthy state. Accumulation of retained-introns was also observed at the pre-symptomatic state of aging in wild-type mice and may be an excellent marker for this state in general.


Assuntos
Envelhecimento/genética , Perfilação da Expressão Gênica/métodos , Marcadores Genéticos/efeitos dos fármacos , Glucuronidase/genética , Fígado/química , Compostos Fitoquímicos/administração & dosagem , Envelhecimento/efeitos dos fármacos , Processamento Alternativo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Resposta ao Choque Térmico , Íntrons , Japão , Fígado/efeitos dos fármacos , Medicina Tradicional , Metabolômica , Camundongos , Modelos Animais , Compostos Fitoquímicos/farmacologia , Precursores de RNA/genética , Análise de Sequência de RNA
12.
Int J Biol Sci ; 17(8): 1925-1939, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34131396

RESUMO

Background: Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) allow entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells and play essential roles in cancer therapy. However, the functions of ACE2 and TMPRSS2 in kidney cancer remain unclear, especially as kidneys are targets for SARS-CoV-2 infection. Methods: UCSC Xena project, the Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases (GSE30589 and GSE59185) were searched for gene expression in human tissues, gene expression data, and clinical information. Several bioinformatics methods were utilized to analyze the correlation between ACE2 and TMPRSS2 with respect to the prognosis of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP). Results: ACE2 expression was significantly upregulated in tumor tissue, while its downregulation was associated with low survival in KIRC and KIRP patients. TMPRSS2 was downregulated in KIRC and KIRP, and its expression was not correlated with patient survival. According to clinical risk factor-based prediction models, ACE2 exhibits predictive accuracy for kidney cancer prognosis and is correlated with metabolism and immune infiltration. In an animal model, ACE2 expression was remarkably downregulated in SARS-CoV-2-infected cells compared to in the control. Conclusion: ACE2 expression is highly correlated with various metabolic pathways and is involved in immune infiltration.it plays a crucial role than TMPRSS2 in diagnosing and prognosis of kidney cancer patients. The overlap in ACE2 expression between kidney cancer and SARS-CoV-2 infection suggests that patients with KIRC or KIRP are at high risk of developing serious symptoms.


Assuntos
Enzima de Conversão de Angiotensina 2/biossíntese , COVID-19/complicações , Carcinoma de Células Renais/complicações , Neoplasias Renais/complicações , Receptores Virais/biossíntese , SARS-CoV-2 , Adulto , Idoso , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/fisiologia , Animais , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Chlorocebus aethiops , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/imunologia , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Modelos Animais , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Especificidade de Órgãos , Prognóstico , Modelos de Riscos Proporcionais , Receptores Virais/genética , Sistema Renina-Angiotensina/fisiologia , Serina Endopeptidases/biossíntese , Serina Endopeptidases/genética , Serina Endopeptidases/fisiologia , Análise Serial de Tecidos , Células Vero
13.
Int J Biol Sci ; 17(8): 2080-2088, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34131407

RESUMO

Coronavirus disease 2019 (COVID-19), an infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a persistent global threat. The transmission of SARS-CoV-2 is wide and swift. Rapid detection of the viral RNA and effective therapy are imperative to prevent the worldwide spread of the new infectious disease. Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated protein (Cas) system is an RNA-directed adaptive immune system, and it has been transformed into a gene editing tool. Applications of CRISPR-Cas system involves in many fields, such as human gene therapy, drug discovery and disease diagnosis. Under the background of COVID-19 pandemic, CRISPR-Cas system shows hidden capacity to fight the emergency in many aspects. This review will focus on the role of gene editing in COVID-19 diagnosis and treatment. We will describe the potential use of CRISPR-Cas-based system in combating COVID-19, from diagnosis to treatment. Furthermore, the limitation and perspectives of this novel technology are also evaluated.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/terapia , Sistemas CRISPR-Cas , Edição de Genes/métodos , Regulação Viral da Expressão Gênica/genética , RNA Viral/análise , SARS-CoV-2/genética , Animais , Fluorometria/métodos , Previsões , Técnicas de Inativação de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Patógeno , Humanos , Camundongos , Camundongos Transgênicos , Modelos Animais , Terapia de Alvo Molecular , Nasofaringe/virologia , Orofaringe/virologia , RNA Viral/genética , RNA Viral/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade
14.
Int J Mol Sci ; 22(10)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069596

RESUMO

Acinetobacter baumannii is a serious nosocomial pathogen with multiple drug resistance (MDR), the control of which has become challenging due to the currently used antibiotics. Our main objective in this study is to determine the antibacterial and antibiofilm activities of the antimicrobial peptide, Octominin, against MDR A. baumannii and derive its possible modes of actions. Octominin showed significant bactericidal effects at a low minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of 5 and 10 µg/mL, respectively. Time-kill kinetic analysis and bacterial viability tests revealed that Octominin showed a concentration-dependent antibacterial activity. Field-emission scanning electron microscopy (FE-SEM) analysis revealed that Octominin treatment altered the morphology and membrane structure of A. baumannii. Propidium iodide (PI) and reactive oxygen species (ROS) generation assays showed that Octominin increased the membrane permeability and ROS generation in A. baumannii, thereby causing bacterial cell death. Further, a lipopolysaccharides (LPS) binding assay showed an Octominin concentration-dependent LPS neutralization ability. Biofilm formation inhibition and eradication assays further revealed that Octominin inhibited biofilm formation and showed a high biofilm eradication activity against A. baumannii. Furthermore, up to a concentration of 100 µg/mL, Octominin caused no hemolysis and cell viability changes in mammalian cells. An in vivo study in zebrafish showed that the Octominin-treated group had a significantly higher relative percentage survival (54.1%) than the untreated group (16.6%). Additionally, a reduced bacterial load and fewer alterations in histological analysis confirmed the successful control of A. baumannii by Octominin in vivo. Collectively, these data suggest that Octominin exhibits significant antibacterial and antibiofilm activities against the multidrug-resistant A. baumannii, and this AMP can be developed further as a potent AMP for the control of antibiotic resistance.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/metabolismo , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Biofilmes/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Sinergismo Farmacológico , Cinética , Viabilidade Microbiana/efeitos dos fármacos , Modelos Animais , Fragmentos de Peptídeos/metabolismo , Peixe-Zebra
15.
Front Immunol ; 12: 620494, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122400

RESUMO

The innate and adaptive immune systems act in concert to protect us from infectious agents and other harmful substances. As a state of temporary or permanent immune dysfunction, immunosuppression can make an organism more susceptible to infection, organ injury, and cancer due to damage to the immune system. It takes a long time to develop new immunomodulatory agents to prevent and treat immunosuppressive diseases, with slow progress. Toll-like receptor 2 (TLR2) agonists have been reported as potential immunomodulatory candidates due to their effective activation of immune responses. It has been demonstrated that thymopentin (TP5) could modulate immunity by binding to the TLR2 receptor. However, the fairly short half-life of TP5 greatly reduces its pharmacological potential for immunosuppression therapy. Although peptide cathelicidin 2 (CATH2) has a long half-life, it shows poor immunomodulatory activity and severe cytotoxicity, which seriously hampers its clinical development. Peptide hybridization is an effective approach for the design and engineering of novel functional peptides because hybrid peptides combine the advantages and benefits of various native peptides. In this study, to overcome all these challenges faced by the parental peptides, six hybrid peptides (CaTP, CbTP, CcTP, TPCa, TPCb, and TPCc) were designed by combining the full-length TP5 with different active fragments of CATH2. CbTP, the most potent TLR2 agonist among the six hybrid peptides, was effectively screened through in silico analysis and in vitro experiments. The CbTP peptide exhibited lower cytotoxicity than either CATH2 or TP5. Furthermore, the immunomodulatory effects of CbTP were confirmed in a CTX-immunosuppressed mouse model, which showed that CbTP has increased immunopotentiating activity and physiological stability compared to the parental peptides. CbTP successfully inhibited immunosuppression and weight loss, increased immune organ indices, and improved CD4+/CD8+ T lymphocyte subsets. In addition, CbTP significantly increased the production of the cytokine TNF-α and IL-6, and the immunoglobulins IgA, IgM, and IgG. The immunoenhancing effects of CbTP were attributed to its TLR2-binding activity, promoting the formation of the TLR2 cluster, the activation of the TLR2 receptor, and thus activation of the downstream MyD88-NF-кB signaling pathway.


Assuntos
Peptídeos/metabolismo , Linfócitos T/imunologia , Timopentina/metabolismo , Receptor 2 Toll-Like/agonistas , Animais , Células Cultivadas , Ciclofosfamida , Citocinas , Feminino , Humanos , Imunidade , Imunidade Humoral , Hospedeiro Imunocomprometido , Imunomodulação , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Peptídeos/imunologia , Células RAW 264.7 , Timopentina/imunologia
16.
Molecules ; 26(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066444

RESUMO

Dental pulp vitality is a desideratum for preserving the health and functionality of the tooth. In certain clinical situations that lead to pulp exposure, bioactive agents are used in direct pulp-capping procedures to stimulate the dentin-pulp complex and activate reparative dentinogenesis. Hydraulic calcium-silicate cements, derived from Portland cement, can induce the formation of a new dentin bridge at the interface between the biomaterial and the dental pulp. Odontoblasts are molecularly activated, and, if necessary, undifferentiated stem cells in the dental pulp can differentiate into odontoblasts. An extensive review of literature was conducted on MedLine/PubMed database to evaluate the histological outcomes of direct pulp capping with hydraulic calcium-silicate cements performed on animal models. Overall, irrespective of their physico-chemical properties and the molecular mechanisms involved in pulp healing, the effects of cements on tertiary dentin formation and pulp vitality preservation were positive. Histological examinations showed different degrees of dental pulp inflammatory response and complete/incomplete dentin bridge formation during the pulp healing process at different follow-up periods. Calcium silicate materials have the ability to induce reparative dentinogenesis when applied over exposed pulps, with different behaviors, as related to the animal model used, pulpal inflammatory responses, and quality of dentin bridges.


Assuntos
Materiais Biocompatíveis/química , Compostos de Cálcio/química , Capeamento da Polpa Dentária , Dentinogênese/efeitos dos fármacos , Silicatos/química , Compostos de Alumínio , Animais , Cerâmica , Materiais Dentários , Polpa Dentária/efeitos dos fármacos , Dentina/química , Dentina Secundária/efeitos dos fármacos , Cães , Combinação de Medicamentos , Humanos , Inflamação , Modelos Animais , Óxidos/farmacologia
17.
Vaccine ; 39(30): 4108-4116, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34120764

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially originated in China in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. Huge efforts were undertaken to bring the COVID-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. We developed a candidate vaccine ZyCoV-D comprising of a DNA plasmid vector carrying the gene encoding the spike protein (S) of the SARS-CoV-2 virus. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme (ACE-2) receptor. The DNA plasmid construct was transformed into E. coli cells for large scale production. The immunogenicity potential of the plasmid DNA has been evaluated in mice, guinea pig, and rabbit models by intradermal route at 25, 100 and 500 µg dose. Based on the animal studies proof-of-concept has been established and preclinical toxicology (PCT) studies were conducted in rat and rabbit model. Preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response including neutralizing antibodies against SARS-CoV-2 and also elicited Th-1 response as evidenced by elevated IFN-γ levels.


Assuntos
COVID-19 , Vacinas de DNA , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , Vacinas contra COVID-19 , China , Escherichia coli , Cobaias , Humanos , Camundongos , Modelos Animais , Coelhos , Ratos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
18.
Ecotoxicol Environ Saf ; 220: 112395, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34102394

RESUMO

Copper (Cu), one of the heavy metals, is far beyond the carrying capacity of the environment with Cu mining, industrial wastewater discharging and the use of Cu-containing pesticides. Intaking excess Cu can cause toxic effects on liver, kidney, heart, but few studies report Cu toxicity on brain tissue. It is noteworthy that most toxicity tests are based on rodent models, but large mammals chosen as animal models has no reported. To explore the relationship of the Cu toxicity and mitochondria-mediated apoptosis on hypothalamus in pigs, the content of Cu, histomorphology, mitochondrial related indicators, apoptosis, and AMPK-mTOR signaling pathway were detected. Results showed that Cu could accumulate in hypothalamus and lead to mitochondrial dysfunction, evidenced by the decrease of ATP production, activities of respiratory chain complex I-IV, and mitochondrial respiratory function in Cu-treated groups. Additionally, the genes and proteins expression of Bax, Caspase-3, Cytc in treatment group were higher than control group. Furthermore, the protein level of p-AMPK was enhanced significantly and p-mTOR was declined, which manifested that AMPK-mTOR signaling pathway was activated in Cu-treated groups. In conclusion, this study illuminated that the accumulation of Cu could cause mitochondrial dysfunction, induce mitochondria-mediated apoptosis and activate AMPK-mTOR pathway in hypothalamus.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Cobre/toxicidade , Hipotálamo/efeitos dos fármacos , Metais Pesados/toxicidade , Mitocôndrias/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose , Caspase 3/metabolismo , Cobre/metabolismo , Citocromos c/metabolismo , Exposição Ambiental , Hipotálamo/metabolismo , Metais Pesados/metabolismo , Mitocôndrias/metabolismo , Modelos Animais , Transdução de Sinais , Suínos , Proteína X Associada a bcl-2/metabolismo
19.
Res Vet Sci ; 138: 116-124, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34129994

RESUMO

Availability of graft materials to fill up osseous defects has always been a concern in orthopaedic surgeries. Deer antler material is a primary bone structure that is easy to collect and could serve as a xenograft. This study examines the behaviour of red deer antler trabecular cylinders in critical size distal femoral epiphyseal defects in 11 rabbits, and evaluates the effect of the decellularization protocols. Two preparation regimes (A and B) were used, with and without lipids and proteins. Radiographs were taken immediately after surgery and after euthanasia 12 weeks post-implantation. Histological evaluation was performed on non-decalcified 10-µm sections with a van Gieson picro-fuchsin staining protocol. A region of interest was defined for each histological section, evaluating the inflammatory reaction, the fibrosis process, and the osteogenesis. Each histological section was microradiographed to evaluate bone contact, presence of synostosis, remodelling and ossification processes. All antler cylinders were successfully implanted. Final radiographic analysis demonstrated osteointegration of most implants at various stages. Light to moderate inflammation around the grafts was noted with only one case showing full encapsulation. A variable degree of intimacy between implant and host bone was evidenced, with bone remodelling and osteogenesis of various intensity being present in all implanted sites. No differences were found between group A and B. Removal of lipids and proteins in the grafts surprisingly did not seem to matter. Decellularization and sterilization protocols may be advocated. Although it presents several limitations, this study shows some promising results regarding antler trabecular bone osteointegration.


Assuntos
Chifres de Veado/química , Remodelação Óssea , Osso Esponjoso/transplante , Cervos , Osteogênese , Coelhos/cirurgia , Transplante Heterólogo/instrumentação , Animais , Masculino , Modelos Animais
20.
Aging (Albany NY) ; 13(12): 16381-16403, 2021 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-34175838

RESUMO

Cardiac senescence is associated with cardiomyopathy which is a degenerative disease in the aging process of the elderly. The present study investigates using multiple experimental approaches whether the natural flavone acacetin could attenuate myocardial senescence in C57/BL6 mice and H9C2 rat cardiac cells induced by D-galactose. We found that the impaired heart function in D-galactose-induced accelerated aging mice was improved by oral acacetin treatment in a dose-dependent manner. Acacetin significantly countered the increased serum advanced glycation end products, the myocardial telomere length shortening, the increased cellular senescence marker proteins p21 and p53, and the reduced mitophagy signaling proteins PINK1/Parkin and Sirt6 expression in aging mice. In H9C2 rat cardiac cells, acacetin alleviated cell senescence induced by D-galactose in a concentration-dependent manner. Acacetin decreased p21 and p53 expression, up-regulated PINK1/Parkin, LC3II/LC3I ratio, pLKB1, pAMPK and Sirt6, and reversed the depolarized mitochondrial membrane potential in aging cardiac cells. Mitophagy inhibition with 3-methyladenine or silencing Sirt6 abolished the protective effects of acacetin against cardiac senescence. Further analysis revealed that acacetin effect on Sirt6 was mediated by Sirt1 activation and increase of NAD+/NADH ratio. These results demonstrate that acacetin significantly inhibits in vivo and in vitro cardiac senescence induced by D-galactose via Sirt1-mediated activation of Sirt6/AMPK signaling pathway, thereby enhancing mitophagy and preserving mitochondrial function, which suggests that acacetin may be a drug candidate for treating cardiovascular disorders related to aging.


Assuntos
Envelhecimento/patologia , Flavonas/farmacologia , Mitofagia/efeitos dos fármacos , Miocárdio/patologia , Acetilação , Adenina/análogos & derivados , Adenina/farmacologia , Adenilato Quinase/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Cardiotônicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Galactose , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Modelos Animais , NAD/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Quinases/metabolismo , Sirtuínas/metabolismo
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