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1.
PLoS One ; 14(9): e0222635, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31568475

RESUMO

Aphids are major pests of wheat crop in Pakistan inflicting considerable economic losses. A better knowledge of landscape scale spatial distribution of aphids and their natural enemies could be used to improve integrated pest management programs. Therefore, the present study aimed to document spatio-temporal variations in populations of wheat aphids and their natural enemies in Pakistan. The 2-year survey study was carried out at ten experimental farms located in five districts of four contrasted agro-ecological zones of eastern Pakistan (Punjab area) i.e. District Chakwal in arid zone, Gujranwala in rice-cropped zone, Faisalabad in central mixed-cropped zone, and Khanewal and Multan in cotton-cropped zone. The dominant aphid species i.e. Schizaphis graminum, Rhopalosiphum padi, R. maidis and Sitobion avenae varied significantly among the five districts surveyed. The population of S. graminum was observed more abundant in arid, R. padi in rice, S. avenae in aird and rice, and R. maidis in cotton-I zones. Aphids ended their population dynamics on 25th March in central mixed-cropped zone and 12th April in other three zones. Various species of natural enemies, mainly Coccinella septumpunctata, C. undecimpunctata, Menochilus sexmaculata, Chrysoperla carnea, Syrphidae and parasitoid mummies were inconsistently observed in four agro-ecological zones. The population of C. septumpunctata, was observed more abundant in rice zone, C. undecimpunctata and C. carnea in cotton-I and arid zones, M. sexmaculata in cotton-I and II zones, Syrphidae in cotton-I zone and parasitoid mummies in rice and arid zones. There were no clear relationships between aphid and the natural enemy populations. The present study may serve as a baseline regarding distribution of wheat aphids and their natural enemies and the results provided insights for further studies on the potential top-down (natural enemies) versus bottom-up (fertilization and irrigation regimes) forces in management of wheat aphids in eastern Pakistan.

2.
Chem Biol Drug Des ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584741

RESUMO

Plant derived natural products are of great interest due to their diversity in modern drug discovery. Sarcococca saligna has been used for the treatment of different diseases. The present study was aimed at isolating phytochemical constituents including Alkaloid-C (1), Dictyophlebine (2), Sarcovagine-D (3) and Saracodine (4) Holaphylline (5) from Sarcococca saligna to investigate the anti-cancer effect of these compounds. These compounds were evaluated for inhibition of aromatase enzyme of breast cancer in assistance by molecular docking simulations to understand molecular interaction between the enzyme and ligands. The IC50 values of compound 1 and 5 were found 138.27±0.01µL and 12.91±0.01µL respectively and both were found active due to their bulky structures in comparison to the active site of aromatase enzyme. The standard drug exemestane showed potent activity in comparison to the test compounds, having IC50 values of 0.052±0.01µL. Both compounds showed favourable electrostatic interactions with the active site of aromatase enzyme but the shape and steric bulk of the compounds were the limiting factor in their inhibitory effects. New lead compounds could be generated after extensive modifications guided by computational and experimental tools as a possible anticancer agents by targeting aromatase enzyme.

3.
Phys Chem Chem Phys ; 21(32): 17821-17835, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31373340

RESUMO

The rise of New Delhi metallo-beta-lactamase-1 (NDM-1) producers is a major public health concern due to carbapenem resistance. Infections caused by carbapenem-resistant enterobacteria (CRE) are classified as a serious problem. To understand the structure and function of NDM-1, an amino acid replacement approach is considered as one of the methods to get structural insight. Therefore, we have generated novel mutations (N193A, S217A, G219A and T262A) near active sites and an omega-like loop to study the role of conserved residues of NDM-1. The minimum inhibitory concentrations (MICs) of ampicillin, imipenem, meropenem, cefotaxime, cefoxitin and ceftazidime for all mutants were found to be reduced 2 to 6 fold, compared to a wild type NDM-1 producing strain. The Km values increased while Kcat and Kcat/Km values were decreased compared to wild type. The affinity as well as the catalysis properties of these mutants were reduced considerably for imipenem, meropenem, cefotaxime, cefoxitin, and ceftazidimem compared to wild type, hence the catalytic efficiencies (Kcat/Km) of all mutant enzymes were reduced owing to the poor affinity of the enzyme. The IC50 values of these mutants with respect to each drug were reduced compared to wild type NDM-1. MD simulations and docking results from the mutant protein models, along with the wild type example, showed stable and consistent RMSD, RMSF and Rg behavior. The α-helix content values of all mutant proteins were reduced by 13%, 6%, 14% and 9% compared to NDM-1. Hence, this study revealed the impact role of active sites near residues on the enzyme catalytic activity of NDM-1.


Assuntos
Antibacterianos/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , beta-Lactamases/química , Antibacterianos/farmacologia , Biocatálise , Domínio Catalítico , Farmacorresistência Bacteriana , Cinética , Testes de Sensibilidade Microbiana , Mutagênese Sítio-Dirigida , Mutação , Ligação Proteica , Estrutura Secundária de Proteína , Termodinâmica , beta-Lactamases/genética , beta-Lactamases/metabolismo
4.
Future Microbiol ; 14: 671-689, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31161792

RESUMO

Aim: To propose newer combinations of antibiotics effective against NDM-1-producing bacterial strains. Materials & methods: Antibiotics combinations were tested by checkerboard assay. NDM-1 protein/enzyme was expressed and purified to perform enzyme kinetics, circular dichroism and fluorescence spectroscopic studies. Results: Doripenem-cefoxitin combination and doripenem-tetracycline combination showed synergistic effect toward NDM-1-producing strains. The catalytic efficiency of NDM-1 enzyme was decreased drastically by 96.6% upon doripenem-cefoxitin treatment and by 35.54% after doripenem-tetracycline treatment. Conformational changes were observed in NDM-1 upon combination treatment. Conclusion: NDM-1-producing bacterial strains show resistance to multiple antibiotics but the combination of doripenem-cefoxitin and doripenem-tetracycline are effective against them. The combination of a carbapenem and cephamycin antibiotic is proposed for future treatment options against bacteria-producing NDM-1.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Cefoxitina/farmacologia , Doripenem/farmacologia , Tetraciclina/farmacologia , beta-Lactamases/efeitos dos fármacos , Bactérias/enzimologia , Bactérias/metabolismo , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Ensaios Enzimáticos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/genética , Cinética , Testes de Sensibilidade Microbiana , Inibidores da Síntese de Proteínas/farmacologia , Termodinâmica , beta-Lactamases/análise
5.
Environ Sci Pollut Res Int ; 26(13): 12673-12688, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30924044

RESUMO

Nickel (Ni) is a naturally occurring metal, but anthropogenic activities such as industrialization, use of fertilizers, chemicals, and sewage sludge have increased its concentration in the environment up to undesirable levels. Ni is considered to be essential for plant growth at low concentration; however, Ni pollution is increasing in the environment, and therefore, it is important to understand its functional roles and toxic effects on plants. This review emphasizes the environmental sources of Ni, its essentiality, effects, tolerance mechanisms, possible remediation approaches, and research direction that may help in interdisciplinary studies to assess the significance of Ni toxicity. Briefly, Ni affects plant growth both positively and negatively, depending on the concentration present in the growth medium. On the positive side, Ni is essential for normal growth, enzymatic activities (e.g., urease), nitrogen metabolism, iron uptake, and specific metabolic reactions. On the negative side, Ni reduces seed germination, root and shoot growth, biomass accumulation, and final production. Moreover, Ni toxicity also causes chlorosis and necrosis and inhibits various physiological processes (photosynthesis, transpiration) and cause oxidative damage in plants. The threat associated with Ni is increased as Ni concentration increases day by day in the environment, particularly in soils; therefore, it would be hazardous for crop production in the near future. Additionally, the lack of information regarding the mechanisms of Ni tolerance in plants further intensifies this situation. Therefore, future research should be focused on approachable and prominent solutions in order to minimize the entry of Ni into our ecosystems.


Assuntos
Recuperação e Remediação Ambiental/métodos , Níquel/fisiologia , Níquel/toxicidade , Plantas/efeitos dos fármacos , Plantas/metabolismo , Ecossistema , Fertilizantes , Níquel/farmacocinética , Oxirredução , Fotossíntese/efeitos dos fármacos , Desenvolvimento Vegetal/efeitos dos fármacos , Poluentes do Solo/toxicidade , Distribuição Tecidual
6.
Proteomics ; : e1800448, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30865368

RESUMO

Epithelial and stromal communications are essential for normal uterine functions and their dysregulation contributes to the pathogenesis of many diseases including infertility, endometriosis, and cancer. Although many studies have highlighted the advantages of culturing cells in 3D compared to the conventional 2D culture system, one of the major limitations of these systems is the lack of incorporation of cells from non-epithelial lineages. In an effort to develop a culture system incorporating both stromal and epithelial cells, 3D endometrial cancer spheroids are developed by co-culturing endometrial stromal cells with cancerous epithelial cells. The spheroids developed by this method are phenotypically comparable to in vivo endometrial cancer tissue. Proteomic analysis of the co-culture spheroids comparable to human endometrial tissue revealed 591 common proteins and canonical pathways that are closely related to endometrium biology. To determine the feasibility of using this model for drug screening, the efficacy of tamoxifen and everolimus is tested. In summary, a unique 3D model system of human endometrial cancer is developed that will serve as the foundation for the further development of 3D culture systems incorporating different cell types of the human uterus for deciphering the contributions of non-epithelial cells present in cancer microenvironment.

7.
PLoS One ; 14(1): e0209188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30601870

RESUMO

BACKGROUND: Cryptosporidium spp are important intestinal protozoan parasites that cause diarrhea in humans, domestic and wild animals. Its infection remains a main public health concern however, the epidemics in human being is still unclear, particularly in developing countries. There are several factors that may enhance the spreading of this parasite in human population especially in young children. METHODOLOGY: A questionnaire was designed to obtain the demographic and clinical data from the participants. A total of 425 stool samples were collected from suspected children (aged 3-10 years) in different hospitals and villages. The initial screening was performed with modified Ziehl Neelsen (mZN) staining technique followed by polymerase chain reaction (PCR). Several potential risk factors were also assessed through the obtained information from suspected individuals. RESULTS: Out of all 425 collected samples, 127 were observed positive by mZN with a prevalence of 29.88% (127/425). The 127 mZN positive samples together with 50 mZN negative samples were processed for molecular analysis through PCR assay. Among them, 71 out of 127 mZN positive samples and 4 out of 50 mZN negative samples were found positive by PCR. The molecular analysis showed that Cryptosporidium parvum was the main cause of infection in children. The results revealed that individuals exposed to diarrhea were more likely to be infected with Cryptosporidium infection while several environmental factors may also play a key role in spreading of this parasite. CONCLUSIONS/SIGNIFICANCE OF THE STUDY: The current high prevalence of Cryptosporidium infection may be due to the lack of awareness and routine based testing in identification of this parasite in District Buner. Further studies are required to determine the importance of Cryptosporidium infection in this area as well as across the country and to find out the possible risk factors that may be associated with the occurrence of this protozoan. There is, however, an urgent need for laboratory-based observational studies to develop a more dynamic estimate of the cryptosporidial disease burden in the region.


Assuntos
Criptosporidiose/epidemiologia , Animais , Animais Domésticos/parasitologia , Criança , Pré-Escolar , Criptosporidiose/parasitologia , Cryptosporidium/genética , Cryptosporidium/isolamento & purificação , DNA de Protozoário/genética , Diarreia/parasitologia , Feminino , Humanos , Masculino , Paquistão/epidemiologia , Prevalência , Fatores de Risco , População Rural , Estações do Ano , Fatores Socioeconômicos , Água/parasitologia , Abastecimento de Água
8.
FEMS Microbiol Lett ; 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30624634

RESUMO

New Delhi metallo-ß-lactamase-1(NDM-1) has been known to hydrolyze nearly all ß-lactam antibiotics, leading to multi drug resistant state. Hence, it is important to search its structure-function relation to control infections caused by such resistant bacterial strains. Mutagenesis is one of the approaches to explore it. No study has been performed to explore the role of non-active-site residues in the enzyme activity. This study includes mutations of three non-active site residues to comprehend its structure and function simultaneously. Three non-active-site laboratory mutants of NDM-1 were generated by site-directed mutagenesis. The MICs of cefotaxime, cefoxitin,imipenem and meropenem were reduced up to 4 fold for these mutants as compared to wild-type. The hydrolytic activity of mutants was also found to be reduced. Mutants showed a significant change in its secondary structure compared to wild type, as determined by CD spectrophotometer. Catalytic property and stability of these mutants were found to be reduced. Hence it revealed an imperative role of non-active-site residues in the enzymatic activity of NDM-1.

9.
Langmuir ; 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30445813

RESUMO

Ice formation and accretion on surfaces is a serious economic issue in energy supply and transportation. Recent strategies for developing icephobic surfaces are intimately associated with superwettability. Commonly, the superwettability of icephobic materials depends on their surface roughness and chemical composition. This article critically categorizes the possible strategies to mitigate icing problems from daily life. The wettability and classical nucleation theories are used to characterize the icephobic surfaces. Thermodynamically, the advantages/disadvantages of superhydrophobic surfaces are discussed to explain icephobic behavior. The importance of elasticity, slippery liquid-infused porous surfaces (SLIPSs), amphiphilicity, antifreezing protein, organogels, and stimuli-responsive materials has been highlighted to induce icephobic performance. In addition, the design principles and mechanism to fabricate icephobic surfaces with superwettability are explored and summarized.

10.
J Biomol Struct Dyn ; : 1-40, 2018 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-29749296

RESUMO

The discovery of NDM-1 and its variants has caused the emergence of antibiotic resistance in the community and hospital setting, causing major concern for health care across the globe. New Delhi Metallo-ß-lactamase is known to hydrolyze almost all ß-lactam antibiotics. Studies have shown the hydrolytic activates of NDM-1 and some of its variants, however a comparative study of these NDM variants has not been explored in detail. Hence, we proposed to check their catalytic activity by performing a comparative study between NDM-1 and its variants. The study was initiated to clone NDM variants (NDM-1, NDM-4, NDM-5, NDM-6 and NDM-7) followed by overexpression of the recombinant proteins to check their hydrolytic properties against ß-lactam antibiotics. The minimum inhibitory concentration of carbapenems antibiotics for blaNDM-5 clone was found four fold increased, whereas no change was observed in the clones having other variants. The hydrolytic activity of carbapenem with NDM-5 variant was found to be augmented as per the kinetics parameter where Km was decreased and kcat, kcat/Km values increased as compared to the NDM-1. Molecular docking studies were employed to identify the variations in the binding ability among all NDM variants with imipenem or meropenem. Simulation studies at 100ns showed a good stability of NDM-5 with imipenem and meropenem as compared to NDM-1. CD spectroscopy data revealed significant changes in the secondary structure of NDM variants. We conclude that NDM-5 showed higher hydrolytic activity as compared to other variants. This study provides a comparative analysis of the severity of NDM producing strains.

11.
Sci Rep ; 8(1): 7030, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29728626

RESUMO

Models that accurately estimate maximum crop biomass to obtain a reliable forecast of yield are useful in crop improvement programs and aiding establishment of government policies, including those addressing issues of food security. Here, we present a new sigmoidal growth model (NSG) and compare its performance with the beta sigmoidal growth model (BSG) for capturing the growth trajectories of eight crop species. Results indicated that both the NSG and the BSG fitted all the growth datasets well (R2 > 0.98). However, the NSG performed better than the BSG based on the calculated value of Akaike's information criterion (AIC). The NSG provided a consistent estimate for when maximum biomass occurred; this suggests that the parameters of the BSG may have less biological importance as compared to those in the NSG. In summary, the new sigmoidal growth model is superior to the beta sigmoidal growth model, which can be applied to capture the growth trajectory of various plant species regardless of the initial biomass values at the beginning of a growth period. Findings of this study will be helpful to understand the growth trajectory of different plant species regardless of their initial biomass values at the beginning of a growth period.

12.
Int J Biol Macromol ; 112: 1272-1277, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29454953

RESUMO

New Delhi metallo ß-lactamase-1 is one of the carbapenemases, causing hydrolysis of almost all ß-lactamase antibiotics. Seventeen different NDM variants have been reported so far, they varied in their sequences either by single or multiple amino acid substitutions. Hence, it is important to understand its structural and functional relation. In the earlier studies role of active site residues has been studied but non-active site residues has not studied in detail. Therefore, we have initiated to further comprehend its structure and function relation by mutating some of its non-active site residues. A laboratory mutant of NDM-1 was generated by PCR-based site-directed mutagenesis, replacing Q to A at 123 position. The MICs of imipenem and meropenem for NDM-1Q123A were found increased by 2 fold as compare to wild type and so the hydrolytic activity was enhanced (Kcat/Km) as compared to NDM-1 wild type. GOLD fitness scores were also found in favour of kinetics data. Secondary structure for α-helical content was determined by Far-UV circular dichroism (CD), which showed significant conformational changes. We conclude a noteworthy role of non-active-site amino acid residues in the catalytic activity of NDM-1. This study also provides an insight of emergence of new variants through natural evolution.


Assuntos
Mutação/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Sítios de Ligação , Dicroísmo Circular , Hidrólise , Imipenem/química , Imipenem/farmacologia , Cinética , Ligantes , Meropeném , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Proteínas Mutantes/química , Estrutura Secundária de Proteína , Tienamicinas/química , Tienamicinas/farmacologia
13.
Biomed Pharmacother ; 100: 461-466, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29454755

RESUMO

The demand for natural medicines has increased because of their limited adverse effects. The aim of study is to explore the antidiabetic potential of isolated steroidal alkaloid from Sarcococca saligna in streptozotocin induced diabetic rats. To determine the antidiabetic activity of steroidal alkaloids, diabetes was induced in rats by injecting streptozotocin intraperitoneally at a dose of 40 mg/Kg. After a week of STZ injection the treatment were started and the 8th day was considered as the 1st day of treatment and up to four weeks the rats were treated with steroidal alkaloids. Animals were divided into five groups, group 1 considered as a control group by receiving normal saline (1 ml/Kg) twice daily and group 2, 3, 4 were treated with active compound sarcovagine-D, saracodine and holaphylline at the dose of 5 mg/Kg subcutaneously twice a day while group 5 was treated with a standard drug glibenclamide at a dose of 1 mg/Kg/day. The result showed that treated group 2 and 4 reduced the glucose level in blood significantly while group 3 showed moderate glucose reduction. The fructosamine level reduced significantly in treating group 4 from the 2nd week of treatment while group 2 and 3 decreased the level significantly in week 4 in diabetic rats. The treated groups showed gradual decreases the glucose level in 1st and 2nd week of oral glucose tolerance test compared to control group. The group receiving holaphylline (4) and sarcovagine-D (2) showed good improvements in blood lipids while the effect of compound on body weight showed less significant improvement. The present study concluded that steroid alkaloids from isolated Sarcococca saligna possess hypoglycemic effect and improve others diabetes associated complications. Together these finding further research is needed using a range of doses to explore the other possible beneficial effects in diabetes mellitus and its molecular mechanism.


Assuntos
Alcaloides/uso terapêutico , Buxaceae , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fitosteróis/uso terapêutico , Extratos Vegetais/uso terapêutico , Alcaloides/isolamento & purificação , Animais , Diabetes Mellitus Experimental/sangue , Avaliação Pré-Clínica de Medicamentos/métodos , Hipoglicemiantes/isolamento & purificação , Masculino , Fitosteróis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Ratos
14.
Chem Cent J ; 12(1): 3, 2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29350299

RESUMO

Ricinus communis (castor plant) is a potent medicinal plant, which is commonly used in the treatment of various ailments. The present study was conducted to appraise the cytotoxicity and mutagenicity of R. communis along with antioxidant and antimicrobial activities. Cytotoxicity was evaluated by hemolytic and brine shrimp assays, whereas Ames test (TA98 and TA100) was used for mutagenicity evaluation. Plant different parts were extracted in methanol by shaking, sonication and Soxhlet extraction methods. The R. communis methanolic extracts showed promising antioxidant activity evaluated as through total phenolic contents (TPC), total flavonoid content (TFC), DPPH free radical inhibition, reducing power and inhibition of linoleic acid oxidation. R. communis seeds, stem, leaves, fruit and root methanolic extracts showed mild to moderate cytotoxicity against red blood cells (RBCs) of human and bovine. Brine shrimp lethality also revealed the cytotoxic nature of extracts with LC50 in the range of 0.22-3.70 (µg/mL) (shaking), 1.59-60.92 (µg/mL) (sonication) and 0.72-33.60 (µg/mL) (Soxhlet), whereas LC90 values were in the range of 345.42-1695.81, 660.50-14,794.40 and 641.62-15,047.80 µg/mL for shaking, sonication and Soxhlet extraction methods, respectively. R. communis methanolic extracts revealed mild mutagenicity against TA98 (range 1975 ± 67 to 2628 ± 79 revertant colonies) and TA100 (range 2773 ± 92 to 3461 ± 147 revertant colonies) strains and these values were 3267 ± 278 and 4720 ± 346 revertant colonies in case of TA98 and TA100 positive controls, respectively. R. communis methanolic extracts prevented the H2O2 and UV to Plasmid pBR322 DNA oxidative damage. Results revealed that R. communis is a potential source of bioactive compounds and in future studies the bioactive compounds will be identified by advanced spectroscopic techniques.

15.
J Biomol Struct Dyn ; 36(7): 1806-1821, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28545327

RESUMO

CTX-M-15 are the most prevalent types of ß-lactamases that hydrolyze almost all antibiotics of ß-lactam group lead to multiple-antibiotic resistance in bacteria. Three ß-lactam inhibitors are available for use in combination with different antibiotics of cephalosporine group against the CTX-M-15-producing strains. Therefore, strategies to identify novel anti ß-lactamase agents with specific mechanisms of action are the need of an hour. In this study, we screened three novel non-ß-lactam inhibitors against CTX-M-15 by multi-step virtual screening approach. The potential for virtually screened drugs was estimated through in vitro cell assays. Hence, we proposed a study to understand the binding mode of CTX-M-15 with inhibitors using bioinformatics and experimental approach. We calculated the dissociation constants (Kd), association constant (Ka), stoichiometry (n) and binding energies (ΔG) of compounds with the respective targets. Molecular dynamic simulation carried out for 25 ns, revealed that these complexes were found stable throughout the simulation with relative RMSD in acceptable range. Moreover, microbiological and kinetic studies further confirmed high efficacies of these inhibitors by reducing the minimum inhibitory concentration (MIC) and catalysis of antibiotics by ß-lactamases in the presence of inhibitors. Therefore, we conclude that these potential inhibitors may be used as a lead molecule for future drug candidates against ß-lactamases-producing bacteria.

16.
Future Med Chem ; 10(2): 221-229, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29202600

RESUMO

New Delhi Metallo ß-lactamase-1 (NDM-1) is a member of the Metallo-ß-lactamase family, capable of catalyzing the hydrolysis of all ß-lactam antibiotics. The rapid dissemination of NDM producers, 'superbugs', has become a worldwide concern to health workers. Seventeen different variants of NDM have been reported so far, across the world. These variants varied in their sequences either by single or multiple amino acid substitutions. This review summarizes the crystal structure of NDM and provides a comparative analysis of all variants. Moreover, we have for the first time highlighted the role of α-helix, ß-sheet and loop structures of NDM enzyme, having different mutations occurred in these regions. The effect of these substitutions on its structure and functional aspect has to be thoroughly understood to design effective inhibitors in future.


Assuntos
beta-Lactamases , Humanos , Conformação Proteica , beta-Lactamases/química , beta-Lactamases/genética , beta-Lactamases/metabolismo
17.
Front Pharmacol ; 8: 875, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29234282

RESUMO

Ethnomedicinal knowledge of plant-derived bioactives could help us in discovering new therapeutic compounds of great potential. Certainly, dandelion has been used in traditional ethno-medicinal systems (i.e., Chinese, Arabian, Indian, and Native American) to treat different types of cancer. Though, dandelion is highly vigorous, but the potential mode of action is still unclear. In the current study, the antiproliferative activity of methanolic extracts of dandelion root (MEDr) on cell viability of HepG2, MCF7, HCT116, and normal Hs27 was investigated. It was observed that MEDr (500 µg/mL) drastically decreased the growth of HepG2 cell line, while the effect on MCF7 and HCT116 cell lines was less pronounced and no effect has been observed in Hs27 cell lines. The MEDr also enhanced the phosphorylation level of AMPK of HepG2 cells, which considered crucial in cancer treatment and other metabolic diseases. The AMPK activation by MEDr noticed in the current study has never been reported previously. The results regarding the number of apoptotic cells (HepG2 cells) were in line with the cell viability test. The current observations clearly demonstrated the potency of MEDr against liver cancer with validation that dandelion could control AMPK and thus cancer in the treated cell lines.

18.
Front Plant Sci ; 8: 1453, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28878793

RESUMO

The sensitivity to abscisic acid (ABA) by its receptors, pyrabactin resistance-like proteins (PYLs), is considered a most important factor in activating the ABA signal pathway in response to abiotic stress. However, it is still unknown which PYL is the crucial ABA receptor mediating response to drought stress in cotton (Gossypium hirsutum L.). Here, we reported the identification and characterization of highly induced ABA receptor GhPYL9-11A in response to drought in cotton. It is observed that GhPYL9-11A was highly induced by ABA treatment. GhPYL9-11A binds to protein phosphatase 2Cs (PP2Cs) in an ABA-independent manner. Moreover, the GhPYL-11A-PP2C interactions are partially disrupted by mutations, proline (P84) and histidine (H111), in the gate-latch region. Transgenic Arabidopsis overexpressing GhPYL9-11A plants were hypersensitive to ABA during seed germination and early seedling stage. Further, the increased in root growth and up regulation of drought stress-related genes in transgenic Arabidopsis as compared to wild type confirmed the potential role of GhPYL9-11A in abiotic stress tolerance. Consistently, the expression level of GhPYL9-11A is on average higher in drought-tolerant cotton cultivars than in drought-sensitive cottons under drought treatment. In conclusion, the manipulation of GhPYL9-11A expression could be a useful strategy for developing drought-tolerant cotton cultivars.

20.
PLoS One ; 12(9): e0184639, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28953894

RESUMO

Wheat being staple food of Pakistan is constantly attacked by major wheat aphid species, Schizaphis graminum (R.), Rhopalosiphum padi (L.) and Sitobion avenae (F.). Due to concern on synthetic chemical use in wheat, it is imperative to search for alternative environment- and human- friendly control measures such as botanical pesticides. In the present study, we evaluated the comparative role of neem seed extract (NSE), moringa leaf extract (MLE) and imidacloprid (I) in the management of the aphid as well as the yield losses parameters in late planted wheat fields. Imidacloprid reduced significantly aphids infestation compared to the other treatments, hence resulting in higher yield, particularly when applied with MLE. The percentages of yield increase in I+MLE treated plots over the control were 19.15-81.89% for grains per spike, 5.33-37.62% for thousand grain weight and 27.59-61.12% for yield kg/ha. NSE was the second most effective control measure in suppressing aphid population, but the yield protected by NSE treatment over the control was comparable to that by imidacloprid. Population densities of coccinellids and syrphids in the plots treated with NSE-2 were higher than those treated with imidacloprid in two out of three experiments during 2013-14. Low predator density in imidacloprid-treated plots was attributed to the lower availability of prey aphids. The efficacy of NSE against aphids varied depending on degree of synchronization among the application timing, the activity of aphids, crop variety and environmental conditions. Despite that, we suggested NSE to be a promising alternative botanical insecticide compared to the most commonly recommended imidiacloprid. Further studies should consider the side effects of biopesticides on non-target organisms in order to provide better management practices in the field.


Assuntos
Afídeos/efeitos dos fármacos , Produtos Agrícolas/parasitologia , Inseticidas/farmacologia , Moringa/química , Extratos Vegetais/farmacologia , Triticum/parasitologia , Animais , Paquistão
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