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1.
Front Pediatr ; 9: 762531, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778152

RESUMO

Introduction: Every year, millions of children die from preventable causes worldwide. According to World Health Organization, injuries are the leading cause of disability and death among all age groups below 60 years. Aim: This study aimed to evaluate the global research outcomes and trends, and some key bibliometric indicators in pediatric trauma. Methods: A descriptive bibliometric analysis study was designed. On June 14, 2021, an electronic search was performed in the Web of Science Core Collection database using the potential searching keywords "Pediatric AND Trauma" in the title field without any limitations. The search was performed using the Boolean search query method. The data were downloaded in plaintext and comma-separated values format. The required graphs were generated using OriginPro 2018. Furthermore, the data were transferred to HistCite™ software for bibliometric analysis. In addition, the obtained data were plotted for network visualization mapping using VOSviewer software version 1.6.15 for windows. Results: A total of 2,269 documents were included in the final analysis. The included documents were authored by 7,894 authors and published in 395 research and academic journals, mainly in the English language (n = 2,222). The main document types were articles (n = 1,276, citations = 18,244), and meeting abstracts (n = 331, citations = 19). Pediatric (n = 2,269) and trauma (n = 2,257) were the most widely used keywords. The most productive year was 2019 (n = 184, citations = 527). The most prolific author was Upperman JS (n = 29, citations = 202). The most attractive journals in pediatric trauma research were The Journal of Trauma and Acute Care Surgery (n = 290, citations = 5,199) and the Journal of Pediatric Surgery (n = 256, citations = 5,088). The most active institute was the University of California System (n = 110). The most dominant country was the United States of America (USA) (n = 1,620, citations = 22,983). The USA and Canada had the highest total link strength, 103 and 70, respectively. Conclusion: This study provides a comprehensive overview of research output in pediatric trauma. The USA continues to dominate scientific research and funding in pediatric trauma. Findings of the current study will help the researchers and clinicians to understand the recent achievements and research frontiers. Collaborative research initiative needs to be established between institutions in developed and developing countries and among researchers.

2.
Clin Genet ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34708404

RESUMO

Biallelic changes in the ZNFX1 gene have been recently reported to cause severe familial immunodeficiency. Through a search of our bio/databank with information from genetic testing of >55 000 individuals, we identified nine additional patients from seven families with six novel homozygous ZNFX1 variants. Consistent with the previously described phenotype, our patients suffered from monocytosis, thrombocytopenia, hepatosplenomegaly, recurrent infections, and lymphadenopathy. The two most severely affected probands also had renal involvement and clinical presentations compatible with hemophagocytic lymphohistiocytosis. The disease was less lethal among our patients than previously reported. We identified two missense changes, two variants predicted to result in complete protein loss through nonsense-mediated decay, and two frameshift changes that likely introduce a truncation. Our findings (i) independently confirm the role of ZNFX1 in primary genetic immunodeficiency, (ii) expand the genetic and clinical spectrum of ZNFX1-related disease, and (iii) illustrate the utility of large, well-curated, and continually updated genotype-phenotype databases in resolving molecular diagnoses of patients with initially negative genetic testing findings.

3.
J Adv Res ; 33: 227-239, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34603792

RESUMO

Background: Because enzymes can control several metabolic pathways and regulate the production of free radicals, their simultaneous use with nanoplatforms showing protective and combinational properties is of great interest in the development of therapeutic nano-based platforms. However, enzyme immobilization on nanomaterials is not straightforward due to the toxic and unpredictable properties of nanoparticles in medical practice. Aim of review: In fact, because of the ability to load enzymes on nano-based supports and increase their renewability, scientific groups have been tempted to create potential therapeutic enzymes in this field. Therefore, this study not only pays attention to the therapeutic and diagnostic applications of diseases by enzyme-nanoparticle (NP) bio-conjugate (abbreviated as: ENB), but also considers the importance of nanoplatforms used based on their toxicity, ease of application and lack of significant adverse effects on loaded enzymes. In the following, based on the published reports, we explained that the immobilization of enzymes on polymers, inorganic metal oxide and hybrid compounds provide hopes for potential use of ENBs in medical activities. Then, the use of ENBs in bioassay activities such as paper-based or wearing biosensors and lab-on-chip/microfluidic biosensors were evaluated. Finally, this review addresses the current challenges and future perspective of ENBs in biomedical applications. Key scientific concepts of review: This literature may provide useful information regarding the application of ENBs in biosensing and therapeutic platforms.

4.
Neurosci Lett ; 764: 136297, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34666120

RESUMO

Intracerebral hemorrhage (ICH) is a severe neurological dysfunction and a medical emergency with a high mortality rate. Minocycline ameliorates deficits in rodent models of acute and chronic neurological diseases. However, the role of minocycline in ICH remains unclear. The extracellular matrix metalloproteinase inducer (EMMPRIN) is a key inflammatory mediator in some neurological diseases, triggering matrix metalloproteinases (MMPs) production. In this study, we aimed to use minocycline to inhibit EMMPRIN and thus the activity of MMPs. Male adult C57BL/6 mice were injected with collagenase type VII or saline into the right basal ganglia and euthanized at different time points. The minocycline was intraperitoneally injected once every 12 h for three days to block the expression of EMMPRIN from two hours after ICH. We found that breakdown of the BBB was most severe 3 days after ICH. The minocycline treatment significantly decreased EMMPRIN and MMP-9 expression, reduced zonula occludens-1 and occludin, and alleviated BBB disruption. Moreover, minocycline treatment displayed a lower brain water content, lesser neurological dysfunction, and smaller injury volume on day 3 than those of the vehicle-treated group. Minocycline also inhibited the activation of microglia/macrophages, infiltration of neutrophils, and production of inflammatory mediators, including tumor necrosis factor alpha and interleukin-1beta. The current study shows that minocycline exhibits protective roles in ICH by decreasing EMMPRIN and MMP-9 expression, alleviating BBB disruption, inhibiting neuroinflammation, areducing neuronal degeneration and death.

5.
Anticancer Drugs ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34520434

RESUMO

Oridonin (ORI) is known to pose anticancer activity against cancer, which could induce the therapeutic impact of chemotherapy drugs. However, such simple combinations have numerous side effects such as higher toxicity to normal cells and tissues. To enhance the therapeutic effects with minimal side effects, here we used ORI in combination with cisplitin (CIS) against different esophageal squamous cell carcinoma (ESCC) cell lines in vitro, to investigate the synergistic anticancer effects of the two drugs against ESCC. Calcusyn Graphing Software was used to assess the synergistic effect. Apoptosis, wound healing and cell invasion assay were conducted to further confirm the synergistic effects of ORI and CIS. Intracellular glutathione (GSH) and reactive oxygen species assay, immunofluorescence staining and western blot were used to verify the mechanism of synergistic cytotoxicity. ORI and CIS pose selective synergistic effects on ESCC cells with p53 mutations. Moreover, we found that the synergistic effects of these drugs are mediated by GSH/ROS systems, such that intracellular GSH production was inhibited, whereas the ROS generation was induced following ORI and CIS application. In addition, we noted that DNA damage was induced as in response to ORI and CIS treatment. Overall, these results suggest that ORI can synergistically enhance the effect of CIS, and GSH deficiency and p53 mutation, might be biomarkers for the combinational usage of ORI and CIS.

6.
Aging (Albany NY) ; 13(18): 21810-21811, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34586082
7.
Biomed Res Int ; 2021: 5521516, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395617

RESUMO

Dibutyl phthalate is an endocrine disruptor used in a wide range of industrial and agriculture applications. The present study focuses on elucidating the effect of subacute exposure (4-weeks) of DBP on insulin and its sensitivity indexes, oxidative status, thyroid function, energy metabolites, serum biochemistry, and anthropometry in rats. A total of 64 rats were divided into 4 treatment groups as mg DBP/Kg body weight per day: (a) 0 mg/Kg (control), (b) 10 mg/Kg (DBP-10), (c) 50 mg/Kg (DBP-50), and (d) 100 mg/Kg (DBP-100). The rats in each treatment (n = 16) were further divided into male (n = 8) and female (n = 8) rats for studying treatment and gender interactions. Intraperitoneal glucose tolerance test (IPGTT) was performed on the 21st day. Anthropometry, nutritional determinants, fasting plasma glucose, fasting plasma insulin, homeostatic model assessment (HOMA), thyroid hormones, energy metabolites, and oxidative status were studied during the experimental period. Two-way ANOVA was used to analyze the data (p < 0.05). Tukey's posthoc test was used for pair-wise comparisons. DBP increased body weight gain and feed efficiency in an inverted nonmonotonic U-shaped fashion. Hyperglycemia and increased blood glucose area under the curve were observed in DBP-100 at 120 minutes in IPGTT. The HOMA also showed a linear monotonic contrast. Thyroxin decreased significantly in the DBP-100 rats, whereas malondialdehyde, nonesterified fatty acids, and beta hydroxyl butyrate were increased with the DBP treatments. In conclusion, DBP could be attributed to the development of hyperglycemia and insulin resistance in rats. Further investigations into the lipid peroxidation pathways can improve our understanding of the mechanisms involved in metabolic disruption.


Assuntos
Dibutilftalato/toxicidade , Hiperglicemia/induzido quimicamente , Resistência à Insulina , Glândula Tireoide/fisiologia , Animais , Feminino , Teste de Tolerância a Glucose , Homeostase/efeitos dos fármacos , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Glândula Tireoide/efeitos dos fármacos , Testes de Toxicidade Subaguda
8.
J Control Release ; 338: 341-357, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34428480

RESUMO

Microneedle arrays have recently received much attention as cancer detection and treatment platforms, because invasive injections and detection of the biopsy are not needed, and drug metabolism by the liver, as well as adverse effects of systemic drug administration, are diminished. Microneedles have been used for diagnosis, vaccination, and in targeted drug delivery of breast cancer. In this review, we summarize the recent progress in diagnosis and targeted drug delivery for breast cancer treatment, using microneedle arrays to deliver active molecules through the skin. The results not only suggest that health and well-being of patients are improved, but also that microneedle arrays can deliver anticancer compounds in a relatively noninvasive manner, based on body weight, breast tumor size, and circulation time of the drug. Moreover, microneedles could allow simultaneous loading of multiple drugs and enable controlled release, thus effectively optimizing or preventing drug-drug interactions. This review is designed to encourage the use of microneedles for diagnosis and treatment of breast cancer, by describing general properties of microneedles, materials used for construction, mechanism of action, and principal benefits. Ongoing challenges and future perspectives for the application of microneedle array systems in breast cancer detection and treatment are highlighted.


Assuntos
Neoplasias da Mama , Administração Cutânea , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Microinjeções , Agulhas , Pele/metabolismo
9.
Future Virol ; 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34181703

RESUMO

Background: Limited details are available regarding the vertical transmission potential of COVID-19 infection in pregnant women. The authors' current study aimed to report the vertical transmission potential of COVID-19 infection in a woman pregnant with twins. Case description: The authors report the case of a 27-year-old woman infected with SARS-CoV-2. The patient was pregnant with dichorionic diamniotic fraternal twins and admitted to Renmin Hospital of Wuhan University, Wuhan, China. After undergoing a cesarean section, the patient gave birth to premature twins, who tested positive for COVID-19 infection. Interpretation: Findings from this case suggest a possibility of intrauterine infection caused by vertical transmission in a woman infected with COVID-19.

10.
Neurol Res ; : 1-8, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112057

RESUMO

Objectives: This article aimed to analyze the relationship between obesity and the efficacy of acute ischaemic stroke patients treated with IVT.Background: Stroke causes morbidity and mortality in large numbers of individuals annually. Intravenous thrombolysis (IVT)with recombinant tissue plasminogen activator (r-tPA) is currently the only approved by the FDA for treatment of acute ischaemic stroke. Researchers have focused on studying the mechanisms associated with ischaemic stroke. Obesity is an established vascular risk factor with increasing prevalence and a huge impact on public health worldwide. It is an independent predictor for ischaemic stroke with a 4% risk increase for each unit augmentation in body mass index (BMI). Therefore, obese patients will constitute an increasing subgroup of candidates for IVT. However, its impact on prognosis in acute ischaemic stroke patients with intravenous thrombolysis did not reach a consensus conclusion.Methods: Systematic literature search of PUBMED databases published before August 2020, was performed to identify studies addressing the role of obesity in acute ischaemic stroke patients treated with IVT. Studies included randomized clinical trials, observational studies, guideline statements, and review articles.Conclusions: Obesity may be related to long-term prognosis of large group of AIS patients treated with IVT. It depends on the scale of clinical study samples, follow-up time, and evaluation criteria.

11.
Int J Biol Macromol ; 185: 813-820, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34186122

RESUMO

The stability of IFN-γ as a therapeutic protein can play a key role on its anticancer effects. Herein, we explored the thermodynamic parameters and conformational stability of IFN-γ in the presence of calycosin, the main active compound of Radix astragali, by different biophysical and theoretical analysis. Afterwards, the improved anticancer effects of IFN-γ-calycosin interaction relative to IFN-γ alone were assessed on hepatocellular carcinoma (HepG2) cell line by MTT and caspase assays. ITC data indicated that upon interaction of calycosin with IFN-γ the binding and thermodynamic parameters were as follows: Kd = 1.9 µM, ΔG° = -32.45 kJ/mol, ΔH° = -11.91 kJ/mol, and TΔS° = 20.54 kJ/mol. ANS/synchronous fluorescence, CD and UV-Vis spectroscopy studies indicated that the interaction between calycosin and IFN-γ caused the folding of the IFN-γ backbone in to a more packed structure with enhanced α-helix content and higher melting temperature (Tm) value. The spectroscopic outcomes were then verified by molecular docking and molecular dynamic analysis. It was also shown that after incubation of the IFN-γ samples at 50 °C for 60 min in the presence of calycosin (5 µM), the IFN-γ-calycosin system showed a significant antiproliferative effects against hepatocellular carcinoma (HepG2) cells through caspase-9/3 activation and this anticancer effect was more pronounced than free IFN-γ. This data may provide useful information about the development of IFN-γ-based therapeutic platforms.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Interferon gama/farmacologia , Isoflavonas/química , Neoplasias Hepáticas/metabolismo , Antineoplásicos/química , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Interferon gama/química , Neoplasias Hepáticas/tratamento farmacológico , Dobramento de Proteína/efeitos dos fármacos , Termodinâmica
12.
Neurol Res ; 43(10): 854-864, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34107863

RESUMO

Objectives: Intracerebral hemorrhage (ICH) is a devastating type of strokes that carries high mortality rates, but effective therapeutic options are still lacking. Here, the adult rat model of ICH was used to investigate the efficacy of a combinational therapy of deferoxamine (DFX) and minocycline.Methods: The ICH was induced by stereotaxic infusion of collagenase into striatum of adult rats. After the induction of ICH, rats were treated with intraperitoneal injection of deferoxamine (50 mg/kg), minocycline (45 mg/kg), or both agents, at 2 hours after ICH and then every 12 hours for up to 3 days. The vehicle group were treated with phosphate-buffered saline (PBS) only. Rats were killed at 1, 2, and 3 day(s) for examination of iron deposition, neuronal death, neurological deficits, the area of brain damage, activation of microglia/macrophages.Results: Our data revealed that the systemic administration of DFX and/or minocycline decreased iron accumulation. And immunofluorescence staining results indicated that drug-treated group significantly decreased the neuronal degeneration, the number of activated microglia/macrophages and the amount of cell death after ICH. In addition, neurological deficits caused by ICH were improved in the presence of DFX and/or minocycline compare with vehicle group. Furthermore, the combination treatment showed better effects in neuroprotection and anti-inflammation when compared to the monotherapy groups.Conclusions: The combination therapy significantly reduces the number of neuronal deaths, suppresses of the activation of microglia/macrophages, decreases iron accumulation in the area around the hematoma, lessening the brain damage area, and improving neurological deficits in ICH.

13.
J Nanobiotechnology ; 19(1): 178, 2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34120609

RESUMO

BACKGROUNDS: One of the most common complications in diabetic nephropathy is generation of high levels of ROS which can be regulated by herbal antioxidants. However, polyphenols like calycosin, the bioactive compound of Radix astragali suffer from low solubility and poor bioavailability. METHODS: Therefore, in the present study, calycosin-loaded nanoliposomes were fabricated and characterized by TEM, DLS and FTIR techniques. Afterwards, the drug loading (DL) and entrapment efficiency (EE), drug release, solubility, stability, and pharmacodynamic assays were performed. Finally, the antinephropathic effects of calycosin-loaded-nanoliposomes on mitochondria of kidney cells were explored by MTT, ROS, MDA, mitochondrial respiratory function assays. RESULTS: The result showed that the size, hydrodynamic radius, zeta potential, EE, and DL were, 80 nm, 133.99 ± 21.44 nm, - 20.53 ± 3.57, 88.37 ± 2.28%, and 7.48 ± 1.19%, respectively. The outcomes of in vitro release assay showed that calycosin-loaded nanoliposomes were significantly slow-release in dialysis media with pH 1.2, pH 6.9 and pH 7.4, at about 30 min, the dissolution of calycosin from nanoliposome became almost complete, and after 2 months, the calycosin-loaded nanoliposomes were still stable. Pharmacokinetic assay revealed that the AUC0-t of calycosin in calycosin-loaded nanoliposome group was 927.39 ± 124.91 µg/L*h, which was 2.26 times than that of the free calycosin group (**P < 0.01). Additionally, the MRT0-t and t1/2 of calycosin in the calycosin-loaded nanoliposome group were prolonged by 1.54 times and 1.33 times than that of free calycosin group, respectively (*P < 0.05). Finally, it was shown that calycosin-loaded nanoliposomes regulated the viability, ROS production, lipid peroxidation and function of mitochondria in kidney cells of diabetic rats as a model of diabetic nephropathy. CONCLUSION: In conclusion it may be suggested that new therapies based on nano-formulated calycosin can restore mitochondrial function which can improve diabetic nephropathy.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Isoflavonas/química , Isoflavonas/farmacologia , Lipossomos/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Animais , Antioxidantes , Disponibilidade Biológica , Diabetes Mellitus Experimental , Liberação Controlada de Fármacos , Medicamentos de Ervas Chinesas , Isoflavonas/uso terapêutico , Rim , Peroxidação de Lipídeos , Masculino , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley
14.
Int J Biol Macromol ; 183: 1184-1190, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33965487

RESUMO

Aggregation of tau protein into the form of insoluble amyloid fibrils is linked with Alzheimer's disease. The identification of potential small molecules that can inhibit tau protein from undergoing aggregation has received a great deal of interest, recently. In the present study, the possible inhibitory effects of liquiritigenin as a member of chiral flavanone family on tau amyloid fibrils formation and their resulting neurotoxicity were assessed by different biophysical and cellular assays. The inhibitory effect of the liquiritigenin against tau amyloid formation was investigated using thioflavin T (ThT) and 1-Anilino-8-naphthalene sulfonate (ANS) fluorescence spectroscopy, Congo red (CR) binding assays, transmission electron microscopy (TEM) analysis, and circular dichroism (CD) spectroscopy. Neurotoxicity assays were also performed against neuron-like cells (SH-SY5Y) using 3-(4,5-Dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) reduction, reactive oxygen species (ROS), catalase (CAT) and caspase-3 activity measurements. We found that liquiritigenin served as an efficient inhibitor of tau amyloid fibrils formation through prevention of structural transition in tau structure, exposure of hydrophobic patches and their associated neurotoxicity mediated by decrease in the production of ROS and caspase-3 activity and elevation of CAT activity. These data may finally find applications in the development of promising inhibitors against amyloid fibril formation and treatment of Alzheimer's disease.


Assuntos
Flavanonas/farmacologia , Neurônios/citologia , Fármacos Neuroprotetores/farmacologia , Proteínas tau/química , Proteínas tau/efeitos dos fármacos , Naftalenossulfonato de Anilina/química , Benzotiazóis/química , Caspase 3/metabolismo , Catalase/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Dicroísmo Circular , Humanos , Microscopia Eletrônica de Transmissão , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Agregados Proteicos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Fluorescência
15.
Aging (Albany NY) ; 13(11): 15336-15352, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34047714

RESUMO

Histone acetylation which regulates about 2-10% of genes has been demonstrated to be involved in tumorigenesis of esophageal squamous cell carcinoma (ESCC). In this study, we investigated the treatment response of ESCC to selective histone deacetylase inhibitor (HDACi) LMK-235 and potential biomarker predicting the treatment sensitivity. We identified tensin-3 (TNS3) which was highly over-expressed in ESCC as one of the down-regulated genes in response to LMK-235 treatment. TNS3 was found positively correlated with the tumor malignancy and poor prognosis in the patients. Silencing TNS3 significantly inhibited ESCC cell proliferation both in vitro and in vivo, sensitizing the treatment response to LMK-235. Our findings provide an insight into understanding the oncogenic role of TNS3 in ESCC and its clinical application for HDAC targeted therapy of ESCC.


Assuntos
Benzamidas/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Inibidores de Histona Desacetilases/uso terapêutico , Tensinas/metabolismo , Animais , Benzamidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Bases de Dados como Assunto , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oncogenes , Fenótipo , RNA Interferente Pequeno/metabolismo
16.
Environ Sci Pollut Res Int ; 28(35): 49179-49190, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33932218

RESUMO

This study provides new insight by introducing the role of fiscal decentralization and natural resources rent in affecting CO2 emissions. For assessing this objective, this paper use panel data from seven highly fiscal decentralized Organization for Economic Cooperation and Development (OECD) countries from 1990 to 2018. For empirical analysis, we use the Westerlund test and cross-sectional autoregressive distributive lag model. In order to ascertain the integration order of variables, the study utilizes the Pesaran second-generation unit-root test. The findings reveal that all the variables are stationary at first difference. The long-run results confirm that fiscal decentralization and natural resources rent improve the atmosphere by reducing CO2 emissions. Moreover, gross domestic product and total natural resources rent increase, while improvement in institutional quality reduces CO2 emissions. For policy implication, this study recommends that transferring the power to the local governments will further reduce CO2 emissions and shift these countries to more environmentally friendly sources.


Assuntos
Carbono , Desenvolvimento Econômico , Dióxido de Carbono , Estudos Transversais , Países Desenvolvidos , Recursos Naturais , Política
17.
Front Bioeng Biotechnol ; 9: 616555, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34026739

RESUMO

Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or weakening of bone tissues, such as in case of traumatic injury, diseases (e.g., osteosarcoma), or old age, adversely affects the individuals quality of life. Although bone has the innate ability to remodel and regenerate in case of small damage or a crack, a loss of a large volume of bone in case of a traumatic injury requires the restoration of bone function by adopting different biophysical approaches and chemotherapies as well as a surgical reconstruction. Compared to the biophysical and chemotherapeutic approaches, which may cause complications and bear side effects, the surgical reconstruction involves the implantation of external materials such as ceramics, metals, and different other materials as bone substitutes. Compared to the synthetic substitutes, the use of biomaterials could be an ideal choice for bone regeneration owing to their renewability, non-toxicity, and non-immunogenicity. Among the different types of biomaterials, nanocellulose-based materials are receiving tremendous attention in the medical field during recent years, which are used for scaffolding as well as regeneration. Nanocellulose not only serves as the matrix for the deposition of bioceramics, metallic nanoparticles, polymers, and different other materials to develop bone substitutes but also serves as the drug carrier for treating osteosarcomas. This review describes the natural sources and production of nanocellulose and discusses its important properties to justify its suitability in developing scaffolds for bone and cartilage regeneration and serve as the matrix for reinforcement of different materials and as a drug carrier for treating osteosarcomas. It discusses the potential health risks, immunogenicity, and biodegradation of nanocellulose in the human body.

18.
J Adv Res ; 30: 171-184, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34026294

RESUMO

Background: Heterocyclic compounds have always been used as a core portion in the development of anticancer drugs. However, there is a pressing need for developing inexpensive and simple alternatives to high-cost and complex chemical agents-based catalysts for large-scale production of heterocyclic compounds. Also, development of some smart platforms for cancer treatment based on nanoparticles (NPs) which facilitate Fenton reaction have been widely explored by different scientists. Magnetic NPs not only can serve as catalysts in the synthesis of heterocyclic compounds with potential anticancer properties, but also are widely used as smart agents in targeting cancer cells and inducing Fenton reactions. Aim of Review: Therefore, in this review we aim to present an updated summary of the reports related to the main clinical or basic application and research progress of magnetic NPs in cancer as well as their application in the synthesis of heterocyclic compounds as potential anticancer drugs. Afterwards, specific tumor microenvironment (TME)-responsive magnetic nanocatalysts for cancer treatment through triggering Fenton-like reactions were surveyed. Finally, some ignored factors in the design of magnetic nanocatalysts- triggered Fenton-like reaction, challenges and future perspective of magnetic nanocatalysts-assisted synthesis of heterocyclic compounds and selective cancer therapy were discussed.Key Scientific Concepts of Review:This review may pave the way for well-organized translation of magnetic nanocatalysts in cancer therapy from the bench to the bedside.


Assuntos
Antineoplásicos/farmacologia , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Catálise , Humanos , Peróxido de Hidrogênio/química , Hipertermia Induzida/métodos , Ferro/química , Fenômenos Magnéticos , Camundongos , Neoplasias/metabolismo , Fototerapia/métodos , Microambiente Tumoral/efeitos dos fármacos
19.
Int J Biol Macromol ; 182: 91-97, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33798579

RESUMO

Protein misfolding and aggregation result in induction of a number of neurodegenerative diseases. In the present study, the anti-fibrillation activity of calycosin and its influence on the amyloid formation of α-synuclein (α-syn) and associated cytotoxicity on neuron-like cells (PC-12) as a model of Parkinson's disease were explored. Therefore, in combination with ThT and ANS fluorescence assay, CD, Congo red absorbance, TEM and cytotoxicity assays (MTT, ROS, SOD activity, CAT activity, GSH content, and caspase-3 activity assays), we showed that calycosin remarkably inhibits α-syn fibril formation through a concentration-dependent manner. The experimental analysis indicated that calycosin exert its antioxidant effects against α-syn amyloid-triggered neurotoxicity by modifying the aggregation pathway toward formation of nontoxic spices via recovering the activity of SOD/CAT and GSH content and reducing the ROS content and caspase-3 activity. This work may provide useful information about the mechanism of α-syn amyloid inhibition by calycosin and pave the way for developing some small molecules-based therapeutic platforms against Parkinson's disease.


Assuntos
Amiloide/metabolismo , Antioxidantes/farmacologia , Isoflavonas/farmacologia , Doença de Parkinson/prevenção & controle , alfa-Sinucleína/metabolismo , Animais , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo , Células PC12 , Doença de Parkinson/metabolismo , Ratos
20.
Genet Med ; 23(8): 1551-1568, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33875846

RESUMO

PURPOSE: Within this study, we aimed to discover novel gene-disease associations in patients with no genetic diagnosis after exome/genome sequencing (ES/GS). METHODS: We followed two approaches: (1) a patient-centered approach, which after routine diagnostic analysis systematically interrogates variants in genes not yet associated to human diseases; and (2) a gene variant centered approach. For the latter, we focused on de novo variants in patients that presented with neurodevelopmental delay (NDD) and/or intellectual disability (ID), which are the most common reasons for genetic testing referrals. Gene-disease association was assessed using our data repository that combines ES/GS data and Human Phenotype Ontology terms from over 33,000 patients. RESULTS: We propose six novel gene-disease associations based on 38 patients with variants in the BLOC1S1, IPO8, MMP15, PLK1, RAP1GDS1, and ZNF699 genes. Furthermore, our results support causality of 31 additional candidate genes that had little published evidence and no registered OMIM phenotype (56 patients). The phenotypes included syndromic/nonsyndromic NDD/ID, oral-facial-digital syndrome, cardiomyopathies, malformation syndrome, short stature, skeletal dysplasia, and ciliary dyskinesia. CONCLUSION: Our results demonstrate the value of data repositories which combine clinical and genetic data for discovering and confirming gene-disease associations. Genetic laboratories should be encouraged to pursue such analyses for the benefit of undiagnosed patients and their families.


Assuntos
Exoma , Deficiência Intelectual , Sequência de Bases , Exoma/genética , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Proteínas do Tecido Nervoso , Fenótipo , Sequenciamento Completo do Exoma
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