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1.
Braz. j. biol ; 82: e238337, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1249249

RESUMO

Abstract Extensive field surveys were carried out to explore the distribution of Leisler's Bat Nyctalus leisleri (Kuhl, 1819) in selected area of FATA regions, Pakistan. Specimens of Leisler's Bat Nyctalus leisleri (Kuhl, 1819) (n5) were collected from Kurram Agency (Shublan) (N33.8229788 E70.1634414) at elevation 1427m and Khyber Agency (Landi Kotel) (N34.0909899 E71.1457517) at elevation 1091m for two years survey extending from May 2013 through August 2015. The mean head and body length, hind foot length, ear length and tail length the Nyctalus leisleri specimens captured from the study area was 65.08 ± 1.58 mm, 44.06 ± 0.52 mm, 8.38 ± 0.60 mm, 13.20 ± 0.99 mm and 39.46 ± 1.46 mm, respectively. For molecular analysis the sequences of COI gene were obtained and analyzed. The mean intraspecific divergences of Nyctalus leisleri was 0.04%. The mean interspecific divergences of Nyctalus noctula and Nyctalus leisleri was 0.2%. The mean concentration of each nucleotides was A = (26.3%), T = (32.8%), G = (15.9%) and C = (25.0%). The mean A+T contents were 59.2%and C+G were 40.9%. In the phylogenetic tree Nyctalus leisleri and Nyctalus noctula clustered with significant bootstrap support value.


Resumo Extensas pesquisas de campo foram realizadas para explorar a distribuição do morcego de Leisler Nyctalus leisleri (Kuhl, 1819), em uma área selecionada das regiões das FATA, Paquistão. Espécimes do morcego de Leisler Nyctalus leisleri (Kuhl, 1819) (n = 5) foram coletados na Agência Kurram (Shublan) (N33.8229788 E70.1634414), na elevação 1.427 m, e na Agência Khyber (Landi Kotel) (N34.0909899 E71.1457517), na elevação 1.091 m, por dois anos de pesquisa, estendendo-se de maio de 2013 a agosto de 2015. Os comprimentos médios da cabeça, do corpo, do pé traseiro, da orelha e da cauda dos espécimes de Nyctalus leisleri capturados na área de estudo foram de 65,08 ± 1,58 mm, 44,06 ± 0,52 mm, 8,38 ± 0,60 mm, 13,20 ± 0,99 mm e 39,46 ± 1,46 mm, respectivamente. Para análise molecular, foram obtidas e analisadas as sequências do gene COI. A média das divergências intraespecíficas de Nyctalus leisleri foi de 0,04%. As divergências interespecíficas médias de Nyctalus noctula e Nyctalus leisleri foram de 0,2%. A concentração média de cada nucleotídeos foi A = 26,3%, T = 32,8%, G = 15,9% e C = 25%. Os conteúdos médios de A + T foram de 59,2% e de C + G foram de 40,9%. Na árvore filogenética, Nyctalus leisleri e Nyctalus noctula agruparam-se com um valor significativo de suporte de bootstrap.

2.
J Sci Food Agric ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622444

RESUMO

BACKGROUND: Zinc (Zn) deficiency and low soil fertility are the major factors of low yield in chickpea. This study was conducted to evaluate the effect of Zn application and plant growth promoting bacteria (PGPB) (endophyte Enterobacter sp. MN17) on soil health and aboveground biomass of desi and kabuli chickpea under natural field conditions. Zn was applied as seed priming (0.001M) and soil application (10 kg Zn ha-1 ) with and without PGPB. To determine the impacts of Zn and PGPB on soil biological health, soil microbial biomass carbon (MBC) and soil extracellular enzyme activities were analysed at two growth stages; vegetative (90 days after sowing) and maturity (163 days after sowing). RESULTS: The highest aboveground biomass (5.1 t ha-1 ) was recorded with Zn seed priming + PGPB in kabuli chickpea and in desi chickpea (4.8 t ha-1 ) with Zn seed priming only. The application of Zn significantly increased soil MBC which was higher in kabuli (795 and 731 µg C g-1 ) compared to desi chickpea (655 and 533 µg C g-1 ) at both vegetative and reproductive growth stages, respectively. The highest extracellular soil enzyme activities, ß-glucosidase (4758 nmol g-1 h-1 ), acid phosphatase (5508 nmol g-1 h-1 ), chitinase (5997 nmol g-1 h-1 ) and leucine aminopeptidase (993 nmol g-1 h-1 ) were recorded with Zn seed priming. Of the chickpea types, kabuli chickpea had higher soil extracellular enzyme activities in the rhizosphere than desi chickpea. CONCLUSIONS: Zn seed priming along with PGPB application may improve soil health and chickpea biomass in marginal soils. This article is protected by copyright. All rights reserved.

3.
Plant J ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587326

RESUMO

The Arabidopsis thaliana aldehyde oxidase 3 (AAO3) catalyzes the oxidation of abscisic aldehyde (ABal) to abscisic acid (ABA). Besides ABal, plants generate other aldehydes that can be toxic above a certain threshold. AAO3 knockout mutants (aao3) exhibited earlier senescence but equivalent relative water content compared with wild-type (WT) during normal growth or upon application of UV-C irradiation. Aldehyde profiling in leaves of 24-day-old plants revealed higher accumulation of acrolein, crotonaldehyde, 3Z-hexenal, hexanal and acetaldehyde in aao3 mutants compared with WT leaves. Similarly, higher levels of acrolein, benzaldehyde, crotonaldehyde, propionaldehyde, trans-2-hexenal and acetaldehyde were accumulated in aao3 mutants upon UV-C irradiation. Aldehydes application to plants hastened profuse senescence symptoms and higher accumulation of aldehydes, such as acrolein, benzaldehyde and 4-hydroxy-2-nonenal, in aao3 mutant leaves as compared with WT. The senescence symptoms included greater decrease in chlorophyll content and increase in transcript expression of the early senescence marker genes, Senescence-Related-Gene1, Stay-Green-Protein2 as well as NAC-LIKE, ACTIVATED-BY AP3/P1. Notably, although aao3 had lower ABA content than WT, members of the ABA-responding genes SnRKs were expressed at similar levels in aao3 and WT. Moreover, the other ABA-deficient mutants [aba2 and 9-cis-poxycarotenoid dioxygenase3-2 (nced3-2), that has functional AAO3] exhibited similar aldehydes accumulation and chlorophyll content like WT under normal growth conditions or UV-C irradiation. These results indicate that the absence of AAO3 oxidation activity and not the lower ABA and its associated function is responsible for the earlier senescence symptoms in aao3 mutant.

4.
PLoS One ; 16(8): e0254605, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34398875

RESUMO

The re-emergence of virulent strains of the Infectious Bursal Disease Virus (IBDV) leads to significant economic losses of poultry industry in Pakistan during last few years. This disease causes the infection of bursa, which leads to major immune losses. A total number of 30 samples from five IBD outbreaks during the period of 2019-20 were collected from different areas of Faisalabad district, Pakistan and assayed by targeting the IBD virus VP2 region through RT-PCR. Among all the outbreaks, almost 80% of poultry birds were found positive for the IBDV. The bursa tissues were collected from the infected birds and histopathological examination of samples revealed severe lymphocytic depletion, infiltration of inflammatory cells, and necrosis of the bursa of Fabricius (BF). Positive samples were subjected to re-isolation and molecular characterization of IBDV. The Pakistan IBDV genes were subjected to DNA sequencing to determine the virus nucleotide sequences. The sequences of 100 Serotype-I IBDVs showing nearest homology were compared and identified with the study sequence. The construction of the phylogenetic tree for nucleotide sequences was accomplished by the neighbor-joining method in MEGA-6 with reference strains. The VP2 segment reassortment of IBDVs carrying segment A were identified as one important type of circulating strains in Pakistan. The findings indicated the molecular features of the Pakistan IBDV strains playing a role in the evolution of new strains of the virus, which will contribute to the vaccine selection and effective prevention of the disease.

6.
Pediatr Neurosurg ; 56(4): 385-391, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34077932

RESUMO

BACKGROUND: Spinal arteriovenous malformations (AVMs) are a cause of 20-30 of all spinal vascular malformation. The treatment option for the AVM depends upon the type of AVM. Here, we present a case series to discuss the type, management, and post-operative conclusion of the spinal AVMs. METHOD: Four patients with spinal AVMs were retrospectively reviewed. All 4 patients were with a nidus-type AVM. Treatment for all patients required embolization. Clinical features, imaging, treatment, and clinical results were observed. All 4 patient's clinical outcome was assessed using the Modified Ranked Scale. RESULT: The follow-up after management showed that all four-patient recovered without any residual deficit. All four-patient scored zero (0) on the Modified Ranked Scale. CONCLUSION: Pediatric spinal AVMs are rare and require complex multimodal approach to achieve favorable outcomes.

7.
Accid Anal Prev ; 157: 106132, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34000677

RESUMO

The road traffic injuries are one of the leading cause of death in children and young adults according to the World Health Organization (WHO). The risk of a crash increases approximately four times for drivers using mobile phones during driving. This study investigates the importance of different factors affecting the driver's choice to use mobile phones for conversation during driving in Lahore, Pakistan. A questionnaire survey was conducted to check the tendency of mobile phone usage during driving from different locations of the city. Participants were asked to indicate frequency, risk, importance and emotionality of ten different conversations. A Structural Equation Model (SEM), similar to a previous study, conducted in Beijing, was developed for the frequency of calling and texting during driving with perceived risk of calling and texting, perceived importance and emotionality as predictors. The frequency of different conversations shows that perceived importance of the call mainly influences the driver's choice to make a call during driving in Lahore. The result of the model show that perceived risk has a significant negative effect on driver's decision to call or text in Lahore, similarly to Beijing. The results also indicates that drivers prefer calling on mobile phones in comparison to texting during driving in Lahore.


Assuntos
Condução de Veículo , Telefone Celular , Acidentes de Trânsito , Pequim , Criança , Cidades , Humanos , Paquistão , Adulto Jovem
8.
BMC Vet Res ; 17(1): 139, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794898

RESUMO

BACKGROUND: Cystic echinococcosis (CE) is one of the principal causes of economic loss to the livestock industry because of its morbidity and mortality of food-producing animals and condemnation of important visceral organs. Pakistan being an agricultural country having an extensive livestock sector, is mostly practiced by poor people, which has a fundamental role in the economy. The present study was aimed to conduct a cross-sectional survey and PCR based confirmation of Echinococcus granulosus in sheep, goats, cows, and buffaloes from southern regions (three districts: Lakki Marwat, Bannu, and Karak) of Khyber Pakhtunkhwa, Pakistan. During the study, a total of 2833 animals were examined randomly including; sheep (n = 529), goats (n = 428), cows (n = 1693), and buffaloes (n = 183). Hydatid cysts were collected and examined for the presence of protoscoleces using microscopy. Detection of DNA was performed by using PCR and two mitochondrial genetic markers namely; NAD-1 and COX-1 were amplified. RESULTS: The overall prevalence of CE was found to be (9%) among the examined animals. The hydatid cyst infection was highly prevalent in buffaloes (12%), followed by sheep (10%), cows (9%), and goats (5.1%). Cystic echinococcosis was more prevalent (10%; 96/992) in district Lakki Marwat followed by district Bannu (9%; 112/1246) and Karak (7%; 39/595). Female animals were more likely to be infected with CE (11.6%) than male animals (5.3%) (p = 0.001). Similarly, the infection was higher in the older group of animals as compared to younger (p = 0.001). Mostly (52.2%; n = 129) of hydatid cysts were found in the liver, while (64.4%; n = 159) cysts of the infected animals were infertile. PCR based identification confirmed the presence of E. granulosus sensu stricto (s.s) in the study area. CONCLUSION: Cystic echinococcosis was found to be highly prevalent in southern regions of Khyber Pakhtunkhwa and could be a potential threat to human health. Moreover, molecular sequencing and phylogenetic analyses should be carried out in future to identify the prevailing genotype (s) of E. granulosus s.s.


Assuntos
Doenças dos Animais/epidemiologia , Equinococose/veterinária , Echinococcus granulosus/isolamento & purificação , Doenças dos Animais/parasitologia , Animais , Búfalos , Bovinos , Estudos Transversais , Equinococose/epidemiologia , Echinococcus granulosus/genética , Feminino , Cabras , Masculino , Paquistão/epidemiologia , Reação em Cadeia da Polimerase/veterinária , Prevalência , Ovinos , Zoonoses/epidemiologia
9.
Cancers (Basel) ; 13(6)2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33804681

RESUMO

Anti-angiogenic approaches targeting the vascular endothelial growth factor (VEGF) signaling pathway have been a significant research focus during the past decades and are well established in clinical practice. Despite the expectations, their benefit is ephemeral in several diseases, including specific cancers. One of the most prominent side effects of the current, VEGF-based, anti-angiogenic treatments remains the development of resistance, mostly due to the upregulation and compensatory mechanisms of other growth factors, with the basic fibroblast growth factor (bFGF) being at the top of the list. Over the past decade, several anti-angiogenic approaches targeting simultaneously different growth factors and their signaling pathways have been developed and some have reached the clinical practice. In the present review, we summarize the knowledge regarding resistance mechanisms upon anti-angiogenic treatment, mainly focusing on bFGF. We discuss its role in acquired resistance upon prolonged anti-angiogenic treatment in different tumor settings, outline the reported resistance mechanisms leading to bFGF upregulation, and summarize the efforts and outcome of combined anti-angiogenic approaches to date.

10.
Am J Trop Med Hyg ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33690156

RESUMO

Coronavirus infection (COVID-19) has significantly increased the mortality and morbidity rates worldwide. The present study was conducted to assess the general public's awareness of COVID-19 and its association with mental health, dietary habits, and physical activity. A web-based survey was conducted to gather information about demographics, knowledge about COVID-19, dietary habits, mental health, and anthropometry among the general public of Pakistan. Descriptive statistics, chi-square test, and multiple logistic regression were used for data analysis. The majority of the participants were suffering from anxiety (71.0%) and depression (52.0%) during the COVID-19 pandemic; 32.4% of participants had poor COVID-19-related knowledge. COVID-19 lockdown reduced the physical activity of 66.9% of participants and increased weight of 38.8% of the survey participants. Demographic variables, including age, gender, ethnicity, education, employment, family type, and geographical location, were significantly associated with knowledge about COVID-19 (P < 0.05). Depression was inversely associated with COVID-19 knowledge (P < 0.05). Healthy changes in dietary habits including decreased consumption of fast foods, soft and cola drinks, fruit drinks, cooked meat (outside the home), sugar, and fats, and were associated with increased knowledge of COVID-19. Vitamin C and immunity-boosting supplement consumption were significantly associated with increased knowledge regarding COVID-19 (< 0.05). Inadequate knowledge about COVID-19 and the presence of anxiety and depression were found among most of the study participants. There is a need to conduct educational seminars to limit the health consequences resulting from COVID-19 lockdown.

11.
Mater Sci Eng C Mater Biol Appl ; 120: 111653, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545821

RESUMO

Demand of bioactive materials that may create a bacteria-free environment while healing and regenerating the defect area is increasing day by day. Zirconia is a very interesting material because of its biocompatibility and high fracture toughness. In this research work, zirconia nanoparticles (NPs) have been synthesized using sol-gel method. Molarity of sols is varied in the range of 25 to 125 mM. The effect of acidic and basic nature of sols is studied by maintaining acidic (2) and basic (9) pH. As-synthesized NPs are made soluble in deionized (DI) water using tangerine drops. Dissolved NPs are spin coated onto glass substrate prior to characterization. Pure tetragonal phase, observed under all conditions using basic medium (pH 9), is accompanied by smaller crystallite size and unit cell volume. Presence of stabilized zirconia phase leads to higher value of density and higher mechanical strength. Nanodendrites with distinct features are observed for the sample prepared with high molarity using basic medium. Whereas, soft agglomerated nanodendrites are observed using acidic medium. Optical properties show transmission of 60-80% in the visible and infrared regions for acidic based samples and ~84% for basic samples. Direct energy band gap is varied from 4.96 eV to 5.1 eV in acidic (pH 2) and 4.91 eV to 4.97 eV in basic (pH 9) media. FTIR spectra show the formation of fundamental tetragonal band at 490 cm-1 for basic samples. Antibacterial response of zirconia is tested against E. coli, Streptococcus and Bacillus bacteria. Human teeth, bare and zirconia coated, are tested for their possible weight loss after dipping in various beverages. Zirconia coated tooth shows negligible degradation in hardness and weight after 24 hr dipping period. Thus, coatings prepared using water soluble zirconia (WSZ) nanoparticles, without the use of toxic solvents/reagents, are promising material to be used as protective coatings in biomedical applications.


Assuntos
Escherichia coli , Nanopartículas , Dureza , Humanos , Teste de Materiais , Propriedades de Superfície , Zircônio
12.
FASEB J ; 35(3): e21425, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33566443

RESUMO

Histamine-induced vascular leakage is a core process of allergic pathologies, including anaphylaxis. Here, we show that glycolysis is integral to histamine-induced endothelial barrier disruption and hyperpermeability. Histamine rapidly enhanced glycolysis in endothelial cells via a pathway that involved histamine receptor 1 and phospholipase C beta signaling. Consistently, partial inhibition of glycolysis with 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) prevented histamine-induced hyperpermeability in human microvascular endothelial cells, by abolishing the histamine-induced actomyosin contraction, focal adherens junction formation, and endothelial barrier disruption. Pharmacologic blockade of glycolysis with 3PO in mice reduced histamine-induced vascular hyperpermeability, prevented vascular leakage in passive cutaneous anaphylaxis and protected from systemic anaphylaxis. In conclusion, we elucidated the role of glycolysis in histamine-induced disruption of endothelial barrier integrity. Our data thereby point to endothelial glycolysis as a novel therapeutic target for human pathologies related to excessive vascular leakage, such as systemic anaphylaxis.


Assuntos
Permeabilidade Capilar/fisiologia , Células Endoteliais/efeitos dos fármacos , Glicólise/fisiologia , Histamina/farmacologia , Junções Aderentes/efeitos dos fármacos , Junções Aderentes/metabolismo , Anafilaxia/metabolismo , Anafilaxia/patologia , Animais , Permeabilidade Capilar/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Camundongos , Fosfolipase C beta/metabolismo , Transdução de Sinais/efeitos dos fármacos
13.
Bioinformatics ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33624749

RESUMO

MOTIVATION: Durbin's positional Burrows-Wheeler transform (PBWT) is a scalable data structure for haplotype matching. It has been successfully applied to identical by descent (IBD) segment identification and genotype imputation. Once the PBWT of a haplotype panel is constructed, it supports efficient retrieval of all shared long segments among all individuals (long matches) and efficient query between an external haplotype and the panel. However, the standard PBWT is an array-based static data structure and does not support dynamic updates of the panel. RESULTS: Here, we generalize the static PBWT to a dynamic data structure, d-PBWT, where the reverse prefix sorting at each position is stored with linked lists.We also developed efficient algorithms for insertion and deletion of individual haplotypes. In addition, we verified that d-PBWT can support all algorithms of PBWT. In doing so, we systematically investigated variations of set maximal match and long match query algorithms: while they all have average case time complexity independent of database size, they have different worst case complexities and dependencies on additional data structures. AVAILABILITY: The benchmarking code is available at genome.ucf.edu/d-PBWT. SUPPLEMENTARY INFORMATION: Supplementary Materials are available at Bioinformatics online.

14.
Biomacromolecules ; 22(2): 649-660, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33417429

RESUMO

Alginates, serving as hydrocolloids in the food and pharma industries, form particles at pH < 4.5 with positively charged proteins, such as ß-lactoglobulin (ß-Lg). Alginates are linear anionic polysaccharides composed of 1,4-linked ß-d-mannuronate (M) and α-l-guluronate (G) residues. The impact of M and G contents and pH is investigated to correlate with the formation and size of ß-Lg alginate complexes under relevant ionic strength. It is concluded, using three alginates of M/G ratios 0.6, 1.1, and 1.8 and similar molecular mass, that ß-Lg binding capacity is higher at pH 4.0 than at pH 2.65 and for high M content. By contrast, the largest particles are obtained at pH 2.65 and with high G content. At pH 4.0 and 2.65, the stoichiometry was 28-48 and 3-10 ß-Lg molecules bound per alginate, respectively, increasing with higher M content. The findings will contribute to the design of formation of the desired alginate-protein particles in the acidic pH range.


Assuntos
Alginatos , Ácido Glucurônico , Ácidos Hexurônicos , Concentração de Íons de Hidrogênio , Ligação Proteica
15.
Life Sci ; 271: 119070, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33465388

RESUMO

AIMS: In vivo biodistribution of radio labeled ZrO2 nanoparticles is addressed for better imaging, therapy and diagnosis. Nanoparticles are synthesized by microwave assisted sol-gel technique using Fe3O4 as a stabilizer. Antioxidant assay, hemolytic activity in human blood and biodistribution in rabbits was explored to study the therapeutical as well as in vivo targeted diagnostic applications of as synthesized nanoparticles. MAIN METHODS: Fe3O4 stabilized zirconia nanoparticles are synthesized using microwave assisted sol-gel method. Microwave (MW) powers are varied in the range of 100 to 1000 W. As synthesized nanoparticles are evaluated using different characterizations such as X-ray diffractometer, scanning electron microscope, Raman spectroscopy, impedance analyzer, Vickers micro hardness indenter, FTIR, and UV-Vis spectroscopy. In vitro activity of synthesized nanoparticles is checked in freshly extracted human blood serum. To study biodistribution of Fe3O4 stabilized zirconia nanoparticles in rabbit, technetium-99 m was used for labeling purpose. The labeling efficacy and stability of labeled nanoparticles are also measured with instant thin layer chromatography (ITLC) method. Intravenous injection of 99mTc-Fe3O4 stabilized zirconia nanoparticles (0.2 ml), containing 110 MBq of radioactivity, is performed to study the biodistribution; nanoparticles are injected into the ear vein of animal (rabbit). KEY FINDINGS: Zirconia (ZrO2) nanoparticles (NPs) are stabilized using Fe3O4 that were prepared by means of microwave assisted sol-gel method. Crystallite size (~20 nm) agrees well with the values required to stabilize tetragonal zirconia (t-ZrO2). Volume shrinkage results in high value of hardness (~1369). Dielectric constant values, compatible for biomedical application, are observed for tetragonally stabilized samples. Low value of hemolytic response is observed for Fe3O4 stabilized ZrO2 NPs. 99mTc radio labeled ZrO2 NPs proved to be potential candidate to study biodistribution. Biodistribution studies show stability of radiolabeled NPs in the original suspension as well as in blood serum. CT scan of rabbit is performed for several times to check the biodistribution of NPs with time and survival of rabbit. Results suggest that these NPs can also be used as targeted nanoparticles as well as variants of drug payload carrier. SIGNIFICANCE: Results signify that Fe3O4 stabilized ZrO2 nanoparticles synthesized by microwave assisted sol-gel method may be considered as "all-rounder" nanoplatform and are safe enough to be used in diagnostic as well as therapeutic purposes.


Assuntos
Compostos Férricos/metabolismo , Sequestradores de Radicais Livres/metabolismo , Micro-Ondas , Nanopartículas/metabolismo , Radioimunodetecção/métodos , Zircônio/metabolismo , Animais , Compostos Férricos/síntese química , Humanos , Nanopartículas/química , Coelhos , Tecnécio/metabolismo , Distribuição Tecidual/fisiologia , Difração de Raios X/métodos , Zircônio/química
16.
Eur J Med Chem ; 209: 112866, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33039722

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approximately one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo. We have synthesized and analyzed a library of more than 40 compounds to elucidate the key features responsible for the observed activity. We have also identified FGFR1 as a molecular target that is affected by the presence of these compounds, confirming our data using in silico model. Overall, we envision that these compounds can be further developed for the potential treatment of metastatic breast cancer.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Ureia/análogos & derivados , Ureia/farmacologia , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Desenho de Fármacos , Feminino , Humanos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Relação Estrutura-Atividade , Neoplasias de Mama Triplo Negativas/metabolismo , Ureia/farmacocinética
17.
J Hazard Mater ; 402: 123558, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32759000

RESUMO

Sulfate radical-advanced oxidation processes (SR-AOPs) are emerging technologies for decomposing organic pollutants in water. This study investigated the efficiency of UV/persulfate (UV/S2O82-) process to degrade lindane in water, showing 93.2% lindane removal ([lindane]0 = 3.43 µM, [S2O82-]0 = 100 µM) at a UV fluence of 720 mJ/cm2. The lindane degradation followed first order kinetics and mechanistic studies suggested H-abstraction by SO4•- and Cl removal via C-Cl bond cleavage by UV-C light. Toxicity assessment using ECOSAR program showed toxicity gradually decreased and eventually no significant toxicity remained when all by-products vanished at high UV dose. Removal efficiency of lindane decreased from 93.2% to 38.4, 45.5, 56.0, 84.3 and 88.6%, by adding 1.0 mg/L humic acid or 1.0 mM CO32-, HCO3-, Cl- or SO42-, respectively. Coupling of H2O2 with UV/S2O82- showed a significant synergistic effect with 99.0% lindane removal at a UV fluence of 600 mJ/cm2, using [S2O82-]0 = [H2O2]0 = 50 µM while UV/H2O2 resulted in only 36.6% lindane removal ([lindane]0 = 3.43 µM, [H2O2]0 = 100 µM) at a UV fluence of 720 mJ/cm2. The results indicate that SR-AOP has potential for consideration as a remedial technology to treat persistent chlorinated pesticides such as lindane in contaminated water.

18.
Plants (Basel) ; 9(11)2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33153036

RESUMO

The anthocyanin biosynthesis attracts strong interest due to the potential antioxidant value and as an important morphological marker. However, the underlying mechanism of anthocyanin accumulation in plant tissues is not clearly understood. Here, a rice mutant with a purple color in the leaf blade, named pl6, was developed from wild type (WT), Zhenong 41, with gamma ray treatment. By map-based cloning, the OsPL6 gene was located on the short arm of chromosome 6. The multiple mutations, such as single nucleotide polymorphism (SNP) at -702, -598, -450, an insertion at -119 in the promoter, three SNPs and one 6-bp deletion in the 5'-UTR region, were identified, which could upregulate the expression of OsPL6 to accumulate anthocyanin. Subsequently, the transcript level of structural genes in the anthocyanin biosynthesis pathway, including OsCHS, OsPAL, OsF3H and OsF3'H, was elevated significantly. Histological analysis revealed that the light attenuation feature of anthocyanin has degraded the grana and stroma thylakoids, which resulted in poor photosynthetic efficiency of purple leaves. Despite this, the photoabatement and antioxidative activity of anthocyanin have better equipped the pl6 mutant to minimize the oxidative damage. Moreover, the contents of abscisic acid (ABA) and cytokanin (CK) were elevated along with anthocyanin accumulation in the pl6 mutant. In conclusion, our results demonstrate that activation of OsPL6 could be responsible for the purple coloration in leaves by accumulating excessive anthocyanin and further reveal that anthocyanin acts as a strong antioxidant to scavenge reactive oxygen species (ROS) and thus play an important role in tissue maintenance.

19.
Eur J Dent ; 14(S 01): S27-S33, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33242914

RESUMO

OBJECTIVES: The aim of this study was to evaluate psychological distress caused by the novel coronavirus disease 2019 (COVID-19) pandemic among the adult population residing in Pakistan. MATERIALS AND METHODS: This cross-sectional survey-based study comprised 1,000 adults residing in Pakistan. A questionnaire was formulated and circulated among adult population of Pakistan, the depression and anxiety symptoms using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales were assessed. STATISTICAL ANALYSIS: Independent t-test, cross tabulation, and regression analysis were used to identify variables having impact on PHQ-9 and GAD-7 scores. A p-value of ≤ 0.05 was considered statistically significant. RESULTS: Among 1,000 participants, 573 were males and 427 were females who completed the survey. Majority were restricted to home for more than 40 days. Considerable number of participants reported depressive (540, 54%) and anxiety (480, 48%) symptoms. Gender, age, earnings, and occupation have significant relation with psychological distress, although similar was not found with education levels. CONCLUSION: Psychological distress, a concerning yet addressable issue was found among adults arising amid COVID-19 outbreak. Currently, physical health effects of COVID-19 are being looked, while mental health effects being under-addressed. This issue should be addressed to avoid any psychological impact in future.

20.
Pak J Pharm Sci ; 33(3): 1147-1153, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-33191241

RESUMO

Fifteen benzophenone thiosemicarbazones were synthesized and their in vitro antiglycation activity was evaluated. The most active compound 2 (IC50 = 118.15±2.41µM) showed two folds potent activity than the standard, rutin (IC50 = 294.5±1.5µM). Compounds 1 and 3-7 showed good to moderate antiglycation activity in the range of 204.14 - 488.54µM. These compounds were also evaluated for antioxidant activity. Their structure-activity relationships have been developed. The results reveal the potential of these compounds as leads for further studies towards the development of antidiabetic drugs.

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