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Philadelphia-positive (Ph+) leukemia is a type of blood cancer also known as acute lymphoblastic leukemia (ALL), affecting 20-30% of adults diagnosed worldwide and having an engraved prognosis as compared to other types of leukemia. The current treatment regimens mainly rely on tyrosine kinase inhibitors (TKIs) and bone marrow transplants. To date, several generations of TKIs have been developed due to associated resistance and frequent relapse, with cardiovascular system anomalies being the most devastating complication. Nanotechnology has the potential to address these limitations by the targeted drug delivery and controlled release of TKIs. This study focused on the titanium dioxide (TiO2) and graphene oxide (GO) nanocomposite employment to load nilotinib and ponatinib TKIs for therapy of Ph+ leukemia cell line (K562) and Ba/F3 cells engineered to express BCR-ABL oncogene. Meanwhile, after treatment, the oncogene expressing fibroblast cells (Rat-1 P185) were evaluated for their colony formation ability under 3D conditions. To validate the nanocomposite formation, the TiO2-GO nanocomposites were characterized by scanning electron microscope, DLS, XRD, FTIR, zeta potential, EDX, and element mapping. The TKI-loaded TiO2-GO was not inferior to the free drugs after evaluating their effects by a cell viability assay (XTT), apoptosis induction, and colony formation inhibition. The cell signaling pathways of the mammalian target of rapamycin (mTOR), signal transducers and activators of transcription 5 (STAT5), and extracellular signal-regulated kinase (Erk1/2) were also investigated by Western blot. These signaling pathways were significantly downregulated in the TKI-loaded TiO2-GO-treated groups. Based on the findings above, we can conclude that TiO2-GO exhibited excellent drug delivery potential that can be used for Ph+ leukemia therapy in the future, subject to further investigations.
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Antineoplásicos , Sobrevivência Celular , Grafite , Nanocompostos , Titânio , Grafite/química , Grafite/farmacologia , Titânio/química , Titânio/farmacologia , Nanocompostos/química , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Teste de Materiais , Tamanho da Partícula , Ensaios de Seleção de Medicamentos Antitumorais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , AnimaisRESUMO
This study aims to investigate the impacts of traditional and green economic growth on poverty, income inequalities, and environmental degradation in the case of South Asian economies. In this regard, the study collects data for the period 2000 to 2018 from five South Asian economies (Pakistan, India, Sri Lanka, Nepal, and Bangladesh) from world development indicators (WDI). The study applies second-generation unit root test and co-integration technique, CIPS unit root and Westerlund co-integration tests, to establish the stationarity of the series and co-integration relationship among variables. Furthermore, this study utilized dynamic ordinary least square (DOLS) and fully modified ordinary least square (FMOLS) models to investigate the long-run empirical estimates. The study finds that both traditional economic growth (GDP) and green economic growth (GGDP) have a negative impact on poverty and inequality; however, GGDP contributes more than traditional GDP to reducing poverty and inequality. Moreover, the study shows that economic growth has a positive long-run impact on environmental degradation while GGDP has a negative and significant long-run association with environmental degradation. The study recommends that policymakers should develop policies to develop green economic growth to save the environment and for the reduction in poverty and income inequalities in south Asian economies.
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Dióxido de Carbono , Renda , Dióxido de Carbono/análise , Pobreza , Desenvolvimento Econômico , ÍndiaRESUMO
Climate change is bringing drastic changes to the food availability, accessibility, quality, and stability in the world. Pakistan heavily relies on production of wheat for food security. This study investigates the role of climate change on food security over Punjab regions, Pakistan, from 1979-2020. The study utilized the total production of wheat to measure food security. Moreover, the study utilized mean, maximum, minimum temperature, wind speed, and rainfall as a measurement of climate change. This study utilized auto-regressive distributed lag (ARDL) bound test cointegration approach to test the long-run cointegration, while ARDL model is applied to investigate the short-run relationship among modeled variables. This study adopted Augmented Dicky Fuller (ADF) and Phillips Parron (PP) test to check the stationarity of the data. Moreover, the study ensures reliability and validity of the model by utilizing Breusch-Godfrey serial correlation, Breusch-Pagan-Godfry HSK, and Ramsey RESET test. This study found that wheat cultivated area (0.46*), total irrigated area (2.67***), total un-irrigated area (1.93***), and total area sown ([1.0809**) have a positive and significant long-run impact on food production in all regions of Punjab Pakistan. However, while average, the maximum and minimum temperature is negatively and significantly associated with food production in all regions of Punjab (- 1.07**; - 3.33***; - 1.84**), except northern Punjab, where maximum temperature affects positively food production Punjab. Rainfall negatively and significantly affects food production in northern (- 0.34**) and central and southern (- 0.13***) Punjab. Furthermore, wind speed negatively affects food production in all regions of Punjab (- 0.22**; - 0.21*; - 0.11**), except northern Punjab. This study implies that government should develop policies to increase irrigation facilities and loan facilities to increase the total area sown that will help to increase wheat yield and ensure food security. Moreover, the government should devise policies for large-scale plantations to minimize climate change impacts. The study also suggests new improved varieties of the wheat crop that can survive and flourish in the presence of adverse climatic changes, high temperature, and high wind speed.
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Mudança Climática , Desenvolvimento Econômico , Agricultura , Segurança Alimentar , Paquistão , Reprodutibilidade dos Testes , TriticumRESUMO
Environmental degradation has been the main distress in recent years due to the drastic effect of climate change. To determine the gone thorough impact of industrialization and foreign direct investment on environmental degradation, this study utilized panel data of 55 countries of the Asia-Pacific region from 1995 to 2020 and it applies an autoregressive distributed lag (ARDL) model. The results showed that FDI, in general, has a significant negative impact on the environment and causes to increase in methane and CO2 emissions. Moreover, industrialization has a positive and significant impact on the environment. However, the size of the impact is moderate. This study also concludes that in the Asia-Pacific region, the environment Kuznets curve (EKC) and pollution heaven (PH) hypothesis are accepted. Finally, this study suggests the strict implication of environmental guidelines or the adoption of a new policy would be the key to ensuring the quality of the environment. Furthermore, the results confirmed that most of the panel countries are developing countries and do not have strict environmental management guidelines.
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Desenvolvimento Econômico , Desenvolvimento Industrial , Ásia , Dióxido de Carbono/análise , Meio Ambiente , Poluição Ambiental/análise , Investimentos em SaúdeRESUMO
Schumpeter's idea of creative destruction (CD) explains innovation functions in organisations. This paper investigates the CD concept in engineering firms by explaining how technical opportunity (TO) transforms into corporate entrepreneurship (CE) actions once opportunities have a market orientation (MO). A survey was conducted using a structured questionnaire with 132 managers of engineering firms in Pakistan. Structural Equation Modelling (SEM) using Partial Least Square (PLS) approach has been used to analyse the data. Results reveal that MO and TO exerts a positive influence on CE. MO is the reason for the emergence of TO, which corporate entrepreneurs in engineering firms exploit. CD intensifies the impact of MO on TO significantly. Opportunity recognition in engineering firms is distinguished and bounded by MO and technical viability. Engineering firms need to identify gaps in the market through naturally occurring obsolescence of products and services (CD) to create TO with appropriate MO. This study has revived a classical debate over opportunity recognition by incorporating external factors to propose the CE model. The Schumpeterian opportunity recognition process and CD have been examined for engineering firms.
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Introduction: This study aims to elucidate the employers' perspectives on the key generic employability skills which would enable them to seek graduate jobs and will ensure their professional wellbeing once they enter the job market after acquiring a University degree. Methods: In order to pursue this objective, an exploratory qualitative inquiry was deployed which involved two panel-based discussions. The respondents of each panel discussion were invited through the platforms of the Bahawalpur Chamber of Commerce and Industry (BCCI), and the Chamber of Commerce Rahim Yar Khan. These respondents represented Pharmaceuticals, Agrichemical manufacturers (fertilizers, pesticides), Livestock, Cotton, textiles, and apparel industry which are the main industries in Southern Punjab, Pakistan. Results and discussion: For the purpose of analysis, a thematic analysis was done in the context of grounded theory. Resultantly, the findings of the study reveal an employers' perspective on 10 key generic employability skills as must-have for a Pakistani Millennial graduate including various soft and hard skills, such as-Emotional Intelligence, Flexibility and Adaptability, Multitasking, Computer Literacy and Digital Skills, Information Literacy and Data Analytics, Oral and Written Communication in English and Urdu, Critical Thinking, Positive Politics, Work Ethics and Professionalism, and Commercial awareness. Hence, the study produces implications for the employability stakeholders, including government and academia for a much needed shift from a mere subject-based curriculum to a skill-oriented curriculum and training in the Universities, particularly in the region of Southern Punjab, and all across Pakistan as well.
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This article is aimed to examine the relationship between socioeconomic factors and child mortality in South Asia because the relationship between child mortality and socioeconomic factors cannot be overlooked for better progress. Panel data were obtained from (World Development Indicators) and (Human Development Index) for the period 1990-2017. The data were quantitative. Levin, Lin, and Chu and I'm, Pesaran, and Shin test were used to check the stationarity of data. A cointegration test was applied to check the long-run association. Granger causality test was used to determine the direction of the relationship. Fully modified ordinary least squares and dynamic ordinary least squares techniques were used to examine the long-run and short-run impact of socioeconomic determinants on child mortality. The findings from this study showed the significant impact of education, unemployment, and health expenditure, access to improved water and sanitation facilities, and income inequality on child mortality. Overall results showed that there is a negative association between education and child mortality, access to improved water and access to sanitation facilities and child mortality, and health expenditure and child mortality, but there is a positive association between unemployment and income inequality with child mortality. The rate of child mortality is still very alarming in South Asian countries.
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Fatores Socioeconômicos , Criança , Humanos , ÍndiaRESUMO
The objective of this study is to contribute to the existing debate of green economic growth by empirically investigating the role of cleaner energy production, green innovation, and green trade in green economic growth in the context of South Asian countries. For this purpose, the study collects the data of South Asian Economies for 2000-2018 from different sources such as world development indicators (WDI), International Energy Statistics (IES), and Organization for Economic Co-operation and Development (OECD) statistics. The study applied Pesaran's (2007) second-generation unit root test to test the stationarity of the data. Wasteland's (2007) test of cointegration was applied to examine the long-run association among modeled variables. The study confirmed the long-run association among modeled variables that turn to be stationary at the first differences. Moreover, the study applied fully modified least square (FMOLS) and dynamic least square (DOLS) to estimate the empirical results of the study. Results of the study show that the production of clean energy, green innovation, and green trade positively contributes to the green economic growth of South Asian Economies Graphical abstract.
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Dióxido de Carbono , Desenvolvimento Econômico , Dióxido de Carbono/análise , Índia , Análise dos Mínimos Quadrados , Organização para a Cooperação e Desenvolvimento Econômico , Energia RenovávelRESUMO
Traditional ecological knowledge, linguistic, and sociocultural perspectives are key contributors to environmental sustainability. Therefore, it is essential to identify and preserve this biocultural heritage, especially that of indigenous communities and minorities. We conducted an ethnobotanical survey to document the plant species used by the Balti and Shina communities living in the buffer zone of Deosai National Park (DNP), western Himalayas, Pakistan. A combination of random and purposive sampling techniques was adapted, targeting middle- and old-aged informants. A total of 46 semi-structured interviews were conducted and the gathered data were evaluated using relative frequency of citation (RFC) and through comparison with the ethnomedicinal literature. In total, 47 medicinal plant species belonging to 42 genera and 23 families were recorded. Baltis and Shinas cited 42 and 38 plant species, respectively, that were used to treat various diseases. About 60% of species were common among both communities, but 27.7% and 12.8% were exclusive to Baltis and Shinas, respectively. Considerable heterogeneity was noted in vernacular names, plant part(s) used, preparation, and administration. Ribes alpestre, Aconitum violaceum, Delphinium brunonianum, Thymus linearis, and Swertia petiolata were highly utilized species having RFCs > 50. In addition, 46% of medicinal uses, specifically that of Allardia tomentosa, A. tridactylites, Jurinea dolomiaea, and Gallium boreale, were reported for the first time from the region. Cross-cultural analysis revealed sociocultural gaps between both groups. Relatively, Baltis retained more ethnomedicinal knowledge and their traditional medicinal system is more closely associated with traditional Tibetan medicine. Generally, Balti and Shina communities retain substantial biocultural and ethnological diversity, which has been reflected in the present study. Our findings underline the importance and need for sustainable utilization of natural resources, specifically the plant species of this region. However, an in-depth ethnobotanical investigation may underpin the holistic comparative medical ethnobotany of the entire region.
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Emulsion template-guided strategy has been used to produce porous architectures with exquisite structure, tailored morphology, and exclusive features for ubiquitous applications. Notwithstanding, the practical water remediation is often marred by their transport-limited behavior and fragility. To circumvent these conundrums, we prepared hierarchically porous poly(acrylic acid)-alumina nanocomposite beads by solidifying the droplets of emulsions jointly stabilized by the organic surfactants and alumina nanoparticles. By virtue of their positive charge, the alumina nanoparticles got entrapped within the poly(acrylic acid) scaffolds that excluded the risk of secondary contamination typically observed with conventional nanocomposites. Being amenable to surface modification, the carboxyl moieties of the beaded polymer were further exploited to covalently tether branched polyethylenimine throughout the exterior and interior surface of the porous matrix via a grafting-to approach. The macropores expedite an active fluid flow and easier adsorbate transport throughout the functionalized nanocomposites whose overall higher density of positive charge over a certain pH range electrostatically attracts and effectively adsorbs the negatively charged Cr(VI) complexes and anionic congo red ions/molecules from water. This proof-of-concept synthetic approach and postsynthetic modification offer an improved mechanical robustness to these macrosized multifunctional nanocomposite beads for their easier processing, thereby paving the way for the point-of-use water purification technology development.
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Air pollution brings uncountable serious influences on human life during the last decade. This study is an attempt to compare economic liberalism with economic federalism in examining the problem of air pollution in the Asia-Pacific region. Economic analysts have different views with one school of thought arguing that air pollution is the cause of the failure of a free economy rather than the failure of government regulations, while another supports liberal economics and vice versa. After developing a conceptual framework, the study uses the technique of fuzzy set qualitative comparative analysis (fsQCA) to examine how the rule of law, the size of government, regulatory efficiency, and the openness of the market influence air pollution in countries across the region. The analysis identifies two solutions with government size being found to be a necessary and core condition that influences air pollution. The study thus provides insights and suggests that government spending, taxation, and other financial health policies can be used as key sources to control air pollution in the Asia-Pacific region.
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Poluição do Ar , Poluição do Ar/análise , Ásia , Liberdade , Governo , Humanos , PolíticaRESUMO
The study aims to analyze the mediating role of environmental degradation (ED) in the association between energy consumption (EC) and poverty (POV) in Pakistan. For this purpose, data are collected from different sources such as the global economy and World Bank ranging from 1985 to 2017. Augmented Dickey-Fuller (ADF) test is used for testing the stationarity of data. Results of ADF depict that data are stationary at the level and first difference; so this study adopts the autoregressive distributive lag (ARDL) model bound test for analyzing the long-run and short-run relationship among the modeled variables. The study follows the steps of Baron and Kenny's (1986) method to test the mediation of environmental degradation between energy consumption and poverty. The study utilized the Sobel test and VAF to confirm the mediation. The results indicate a negative and significant impact of energy consumption on poverty. The findings revealed that ED partially mediates the long-run relationship between EC and POV. The study suggests that the government makes the energy accessible to the people to fulfill their basic needs which ultimately reduces poverty. Moreover, the government should make policies to improve the environment as the study found that environmental degradation significantly contributes to poverty.
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Desenvolvimento Econômico , Pobreza , Dióxido de Carbono/análise , Humanos , PaquistãoRESUMO
BACKGROUND: Frontline healthcare workers (FHCWs) are at an increased risk of contracting COVID-19. We aimed to assess the stress and psychological impact of the COVID-19 pandemic among FHCWs. METHODS: This was an exploratory hospital-based study. A semistructured e-questionnaire was developed and shared through emails, WhatsApp groups, Facebook, and Twitter. The study instruments used were stress questionnaire and the impact of event scale-revised. RESULTS: We received 133 valid responses. A total of 81 (61.4%) of the respondents were single, 74 (55.6) were male, 70 (52.6%) were between 20 and 29 years of age, and 91 (68.4%) were from urban background. A total of 83 (62.4%) of respondents were doctors and 28 (21.1%) were registered nurses. A total of 36 (27.1%) were posted in emergency and 34 (25.6%) were in the in-patient department. Feeling sad and pessimistic, feeling of being avoided by others, the burden of change in the quality of work, and worrying whether the family will be cared for in their absence were significantly more in nurses as compared to the doctors. Stress due to burden in an increase in the quantity of work was seen more in FHCWs working in the swab collection center as compared to those working in the in-patient department, emergency, or theaters. Severe psychological impact was seen in 81 (60.9%) of FHCWs. The psychological impact was significantly more in males and in those who were married. It was also significantly related to the place of posting. CONCLUSION: More than half of the FHCWs had a severe psychological impact owing to COVID-19. The psychological impact was more in males and those who were married, and it was related to the place of posting of the FHCWs. Nurses had significantly higher stress as compared to doctors.
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Benzamides and tryptamine are biologically significant compounds, therefore, various benzamide analogous of tryptamine have been efficiently synthesized using tryptamine and different benzoyl chlorides, in order to find new biologically active compounds. The resulting products were then characterized by melting point determination, calculation of Rf values and LC-MS techniques. At last, structure activity relationship (SAR) of the synthesized compounds was evaluated against two microbial strains; Bacillus subtilis and Aspergillus niger. All the five prepared products have shown high yield, sharp characterization and significant resistance against the growth of tested microorganism, providing a new range of tryptamine based benzamide derivatives having significant antimicrobial activities.
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Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Benzamidas/síntese química , Benzamidas/farmacologia , Triptaminas/síntese química , Triptaminas/farmacologia , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/crescimento & desenvolvimento , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Cromatografia Líquida , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Temperatura de TransiçãoRESUMO
AIMS AND OBJECTIVES: Variations in drug metabolizing genes are known to have a clinical impact on AED therapy. We genotyped normal and epileptic patient cohorts of monoethnic population of Kashmir valley for CYP2C9 gene and allelic polymorphism and investigated the effect of CYP2C9*2 and *3 polymorphism on the Pharmacokinetic and therapeutic and/or adverse pharmacodynamic responses to Phenytoin in the idiopathic epilepsy patients. METHODS: PCR-RFLP methods were used for genotyping of 121 normal controls and 92 idiopathic epilepsy patients for CYP2C9*2 and *3 polymorphism, the results were validated by direct sequencing. Phenytoin pharmacokinetic (PK) analysis in idiopathic epilepsy patients was done using a validated EMIT assay technique. Pharmacodynamic analysis was done by evaluating clinical response to phenytoin therapy and ADR monitoring. RESULTS: The respective frequencies of CYP2C9 *1, *2, and *3 alleles were 64%, 6.6%, 29.3%, and 58%, 9.8%, 32.6% in controls and idiopathic epilepsy patients from Kashmir valley. PK analysis revealed that AUC0â4 was a better surrogate biomarker of CYP2C9 metabolizer status compared to C4 and C0 concentrations alone. A comparison of âphenytoin response categoriesâ among CYP2C9 Wild and Heterozygous groups did not reveal any significant difference between the groups (p=0.3800). CONCLUSION: CYP2C9* 3 was the most frequent mutant allele found in healthy controls and idiopathic epilepsy patients of ethnic Kashmiri population. CYP2C9 genotype based phenytoin therapy is highly relevant in Kashmiri population due to a high incidence of genetic variations associated with therapeutic and adverse responses to phenytoin. Phenytoin AUC0â4 tends to correlate better with genetic polymorphism of CYP2C9.
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Anticonvulsivantes/farmacocinética , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP2C9/metabolismo , Epilepsia/tratamento farmacológico , Farmacogenética , Farmacovigilância , Fenitoína/farmacocinética , Polimorfismo Genético , Anticonvulsivantes/efeitos adversos , Área Sob a Curva , Biotransformação , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Humanos , Índia , Taxa de Depuração Metabólica , Fenótipo , Fenitoína/efeitos adversos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
In general, benzothiazole derivatives have attracted great interest due to thier pharmaceutical and biological importance. New 2-amino-6-arylbenzothiazoles were synthesized in moderate to excellent yields via Suzuki cross coupling reactions using various aryl boronic acids and aryl boronic acid pinacol esters and the antiurease and nitric oxide (NO) scavenging activity of the products were also examined. The most active compound concerning urease enzyme inhibition was 6-phenylbenzo[d]thiazole-2-amine 3e, with an IC50 value of 26.35 µg/mL. Compound 3c, 6-(4-methoxyphenyl) benzo[d]thiazole-2-amine, exhibited the highest nitric oxide percentage scavenging at 100 µg/mL.
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Benzotiazóis/síntese química , Paládio/química , Urease/química , Aminas , Benzotiazóis/química , Ácidos Borônicos/química , Catálise , Sequestradores de Radicais Livres/química , Estrutura Molecular , Óxido Nítrico/química , Urease/antagonistas & inibidoresRESUMO
Two very distinct chemical reactions, yet a single catalyst: A gold complex promotes the formation of tertiary enamines from a variety of terminal and internal alkynes. Subsequent addition of a terminal alkyne to the reaction mixture affords allenes (see scheme).
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Alcadienos/síntese química , Alcinos/química , Aminas/química , Ouro/química , Compostos Organometálicos/química , Alcadienos/química , Catálise , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos Organometálicos/síntese químicaRESUMO
A series of mono- and dicarbene gold(I) complexes of types Au(CAAC)(Cl) [CAAC = cyclic (alkyl)(amino)carbene] (1) and [Au(CAAC)(2)](+)[X](-) (X = Cl, AuCl(2)) (2) have been prepared through reaction of AuCl(SMe(2)) with free carbenes a-e, and structurally characterized by single X-ray diffraction studies (1a, 1b, 2d, 2e). In addition two new free cyclic (alkyl)(amino)carbenes (c and e) have been synthesized.
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Addition of a sterically demanding cyclic (alkyl)(amino)carbene (CAAC) to AuCl(SMe(2)) followed by treatment with [Et(3)Si(Tol)](+)[B(C(6)F(5))(4)](-) in toluene affords the isolable [(CAAC)Au(eta(2)-toluene)](+)[B(C(6)F(5))(4)](-) complex. This cationic Au(I) complex efficiently mediates the catalytic coupling of enamines and terminal alkynes to yield allenes and not propargyl amines as observed with other catalysts. Mono-, di-, and tri-substituted enamines can be used, as well as aryl-, alkyl-, and trimethylsilyl-substituted terminal alkynes. The reaction tolerates sterically hindered substrates and is diastereoselective. This general catalytic protocol directly couples two unsaturated carbon centers to form the three-carbon allenic core. The reaction most probably proceeds through an unprecedented "carbene/vinylidene cross-coupling."