Differential Effect of 4H-Benzo[d] [1, 3]oxazines on the Proliferation of Breast Cancer Cell Lines.

BACKGROUND: A family of 4H-benzo[d][1,3]oxazines were obtained from a group of N-(2-alkynyl)aryl benzamides precursors via gold(I) catalysed chemoselective 6-exo-dig C-O cyclization. METHOD: The precursors and oxazines obtained were studied in breast cancer cell lines MCF-7, CAMA-1, HCC1954 and SKBR-3 with differential biological activity showing various degrees of inhibition with a notable effect for those that had an aryl substituted at C-2 of the molecules. 4H-benzo[d][1,3]oxazines showed an IC50 rating from 0.30 to 157.4 µM in MCF-7, 0.16 to 139 in CAMA-1, 0.09 to 93.08 in SKBR-3, and 0.51 to 157.2 in HCC1954 cells. RESULTS: We observed that etoposide is similar to benzoxazines while taxol effect is more potent. Four cell lines responded to benzoxazines while SKBR-3 cell line responded to precursors and benzoxazines. Compounds 16, 24, 25 and 26 have the potent effect in cell proliferation inhibition in the 4 cell lines tested and correlated with oxidant activity suggesting a possible mechanism by ROS generation. CONCLUSION: These compounds represent possible drug candidates for the treatment of breast cancer. However, further trials are needed to elucidate its full effect on cellular and molecular features of cancer.

Institutional quality, oil price, and environmental degradation in MENA countries moderated by economic complexity and shadow economy.

This paper aims to analyze the link between environmental degradation and institutional quality and the price of oil moderated by economic complexity and the underground economy. We use quantile regressions with annual panel data for 15 countries in the Middle East and North Africa during 1995-2021. The findings indicate that institutional quality, economic complexity, and output positively and heterogeneously impact environmental degradation. However, the square of production has a negative impact, confirming an inverted U relationship between production and environmental degradation. Likewise, we find that the price of oil and the underground economy have a negative and heterogeneous impact on environmental degradation. Based on our results, a potential recommendation for policymakers is that the institutional framework of Middle Eastern and North African countries should be accompanied by a more significant concern for the environment instead of prioritizing extractive growth that is detrimental to the environment's environmental sustainability. Likewise, economic diversification will mitigate environmental degradation and improve formal employment. Our findings are relevant to policymakers and researchers interested in promoting ecological sustainability.

Metformin, a biological and synthetic overview.

Metformin is the most widely known anti-hyperglycemic, officially acquired by the USA government in 1995 and in 2001 it became the most prescribed treatment for type II diabetes. But how did it become the must-use drug for this disease in such a short period of time? it all started with traditional medicine, by using a plant known as "goat's rue" for the reduction of blood glucose levels. Its use arose in 1918 and evolved to the metformin synthesis in laboratories a couple of years later, using very rudimentary methods which involved melting and strong heating. Thus, a first synthetic route that allowed the preparation of the initial metformin derivates was established. Some of these resulted toxics, and others outperformed the metformin, reducing the blood glucose levels in such efficient way. Nevertheless, the risk and documented cases of lactic acidosis increased with metformin derivatives like buformin and phenformin. Recently, metformin has been widely studied, and it has been associated and tested in the treatment of type II diabetes, cancer, polycystic ovarian syndrome, cell differentiation to oligodendrocytes, reduction of oxidative stress in cells, weight reduction, as anti-inflammatory and even in the recent COVID-19 disease. Herein we briefly review and analyze the history, synthesis, and biological applications of metformin and its derivates.

Gold(I)-Catalyzed Synthesis of 4H-Benzo[d][1,3]oxazines and Biological Evaluation of Activity in Breast Cancer Cells.

The first gold(I)-catalyzed cycloisomerization procedure applied to the synthesis of substituted 4H-benzo[d][1,3]oxazines has been developed starting from N-(2-alkynyl)aryl benzamides. The chemoselective oxygen cyclization via the 6-exo-dig pathway yielded the observed heterocycles in modest to good chemical yields under very mild reaction conditions. The obtained oxazines were assayed on the breast cancer (BC)-derived cell lines MCF-7 and HCC1954 with differential biological activity. The newly synthesized 4H-benzo[d][1,3]oxazine compounds showed several degrees of cell proliferation inhibition with a remarkable effect for those compounds having a substituted aryl at C-2 of the molecules. The 4H-benzo[d][1,3]oxazines showed an IC50 ranking from 3.1 to 95 µM in MCF-7 and HCC1954 cells. These compounds represent potential drug candidates for BC treatment. However, additional assays are needed to elucidate their complete effect over the cellular and molecular hallmarks of cancer.

An analysis of the asymmetric effects of natural gas consumption on economic growth in Pakistan: A non-linear autoregressive distributed lag approach.

Natural gas is a vital energy resource that is used to produce the national output of Pakistan. On the other hand, since natural gas is a relatively cleaner energy resource compared to oil and coal, enhancing the level of natural gas consumption can be expected to promote economic growth while somewhat improving environmental quality in the process. Hence, it is pertinent to assess the economic growth effects associated with the consumption of such comparatively cleaner energy resources. Against this background, the main objective of this paper is to explore the asymmetric effects of natural gas consumption, controlling for financial development, on Pakistan's economic growth figure over the 1965-2019 period. The results from the Augmented Dickey-Fuller, Phillips-Perron, and Zivot-Andrews unit root tests confirm a mixed order of integration among the variables. Besides, the bounds test and the Gregory-Hansen co-integration analysis reveal evidence of long-run associations between economic growth, natural gas consumption, and financial development in the context of Pakistan. Moreover, the outcomes from the nonlinear autoregressive distributed lag model analysis show that in the short-run, positive changes in the natural gas consumption levels increase Pakistan's economic growth. On the other hand, in the long-run, positive and negative changes in natural gas consumption levels increase and decrease the nation's economic growth level, respectively. On the other hand, both positive and negative changes in the financial development level are found to reduce Pakistan's economic growth level in the long run only. Furthermore, the Hacker-Hatemi-J causality analysis verifies that natural gas consumption causally influences the economic growth level in Pakistan; thus, verifying the energy consumption-led growth phenomenon. In line with these key findings, several policy level suggestions are put forward for Pakistan to enhance its natural gas consumption level in order to boost its economic growth rate in the future.

The heterotrimeric G-protein beta subunit Gpb1 controls hyphal growth under low oxygen conditions through the protein kinase A pathway and is essential for virulence in the fungus Mucor circinelloides.

Mucor circinelloides, a dimorphic opportunistic pathogen, expresses three heterotrimeric G-protein beta subunits (Gpb1, Gpb2 and Gpb3). The Gpb1-encoding gene is up-regulated during mycelial growth compared with that in the spore or yeast stage. gpb1 deletion mutation analysis revealed its relevance for an adequate development during the dimorphic transition and for hyphal growth under low oxygen concentrations. Infection assays in mice indicated a phenotype with considerably reduced virulence and tissue invasiveness in the deletion mutants (Δgpb1) and decreased host inflammatory response. This finding could be attributed to the reduced filamentous growth in animal tissues compared with that of the wild-type strain. Mutation in a regulatory subunit of cAMP-dependent protein kinase A (PKA) subunit (PkaR1) resulted in similar phenotypes to Δgpb1. The defects exhibited by the Δgpb1 strain were genetically suppressed by pkaR1 overexpression, indicating that the PKA pathway is controlled by Gpb1 in M. circinelloides. Moreover, during growth under low oxygen levels, cAMP levels were much higher in the Δgpb1 than in the wild-type strain, but similar to those in the ΔpkaR1 strain. These findings reveal that M. circinelloides possesses a signal transduction pathway through which the Gpb1 heterotrimeric G subunit and PkaR1 control mycelial growth in response to low oxygen levels.

Greenhouse gas emissions, non-renewable energy consumption, and output in South America: the role of the productive structure.

Most of the countries of South America depend heavily on mining and agriculture, which develops through the destruction of the forest. The expansion of the agricultural frontier is more visible in countries with proximity to the Amazon. Otherwise, the increase in urban primacy and real income per capita has led to an increase in the use of non-renewable energy in recent decades. The interest in quantifying greenhouse gas emissions has increased, oriented towards the search for mechanisms that mitigate the irreversible effects of climate change. In this context, the objective of this research is to examine the causal link among non-renewable energy consumption and real GDP per capita in greenhouse gas emissions in ten countries of South America during 1971-2014. In addition, we group the countries according to their productive structure and we incorporate the structural changes of each country in the econometric estimations, allowing to significantly improve the understanding of the sources of greenhouse gases. We use cointegration and causality techniques for time series data, and we found that there is a relationship of short- and long-term equilibrium between the three variables in all countries. The causality test indicates that in Bolivia, Peru, and Uruguay, there is causality from the consumption of non-renewable energy to greenhouse gas emissions. Likewise, in Venezuela and the agricultural countries, GDP causes greenhouse gas emissions. An implication of the public policy derived from this research is that most of the countries of South America can promote a change in the energy matrix to contribute to the mitigation of greenhouse gas emissions without limiting economic growth.

Sporulation on blood serum increases the virulence of Mucor circinelloides.

Mucor circinelloides is an opportunistic human pathogen that is used to study mucormycosis, a rare but lethal infection in susceptible immunosuppressed patients. However, the virulence characteristics of this pathogen have not been fully elucidated. In this study, sporangiospores (spores) produced on YPG medium supplemented with native blood serum increased the virulence of M. circinelloides compared with spores produced on YPG supplemented with denatured blood serum or on YPG alone. The spores produced from YPG supplemented with native blood serum increased nematode death and led to significant increases in interleukin (IL)-6, IL-1ß, macrophage inhibitory protein-2, and tumour necrosis factor α mRNA levels in liver and lung tissues from infected diabetic mice compared with those in tissues from animals infected with spores produced in the presence of YPG supplemented with denatured blood serum or of YPG alone. Moreover, spores produced from cultures supplemented with native blood serum showed increased germination rates and longer hyphae compared with other spores. The spores produced in YPG supplemented with native blood serum also enhanced resistance to stress factors and H2O2 and increased thermotolerance compared with spores produced under other conditions. In addition, spores produced in presence of blood serum increased the ability of the pathogen to survive in the presence of macrophages. Taken together, our results showed that these factors were important features for fungal virulence in humans and suggested that thermolabile components in the blood serum may induce M. circinelloides virulence.

Prácticas de alimentación en lactantes del Hospital nacional Dr. Mario Catarino Rivas / Feeding Practices in Infants at the Dr. Mario Catarino Rivas National Hospita

Antecedentes: El desarrollo de la alimentación es una progresión aprendida de comportamientos que dependen tanto de la integridad estructural-neurológica como del temperamento del individuo y su ambiente. El objetivo primordial de la alimentación es la adquisición de nutrientes para lograr un crecimiento óptimo, la adquisición de habilidades oromotoras y hábitos alimenticios adecuados. Objeti- vo: identi car las prácticas de alimentación y estado nutricional de los menores de 24 meses. Pacientes y métodos: estudio descriptivo analítico en menores de 24 meses ingresados en la Sala de Lactantes Hospital Nacional Dr. Mario Catarino Rivas (HNMCR) durante el mes de abril a mayo del 2016. Se realizó muestreo no probabilístico por conveniencia de 148 sujetos. Resultados: El 75% de los niños recibieron lactancia materna (de forma exclusiva y no exclusiva) durante un promedio de 4 meses. Se inició con sustitutos inadecuados de leche materna en el 36% por consejo de la abuela o decisión propia de la madre. Se inició la ablactación precoz en 16% (n=23) y temprana en 40%(n=64), 13% inició la ablactación con sopa maggie o sopa de frijoles. Hubo exposición antes del año a la naranja 56%, piña (21%), mantequilla (59%) y queso (48%) entre otros. 36.5% tuvieron problemas nutricionales. La probabilidad de tener problemas nutricionales es 2 veces mayor con la ablactación precoz y el uso de leche entera. Conclusiones: las prácticas de alimentación en lactantes del HNMCR son inadecuadas, incompletas e insuficientes...(AU)

Consequences of chronic nasal obstruction on the laryngeal mucosa and voice quality of 4- to 12-year-old children.

INTRODUCTION: Dysphonia affects 6% to 23% of children, and chronic nasal obstruction may participate in its pathophysiology. OBJECTIVES: To study the effects of chronic nasal obstruction on children's vocal quality. SUBJECTS AND METHODS: Two study groups were formed: nasal obstruction group (NOG), consisting of 60 children aged 4-12 years with important symptoms of chronic nasal obstruction; and a control group (CG), similar in gender and age range, consisting of healthy students without nasal, vocal, or auditory symptoms. The parents answered a questionnaire containing questions concerning their children's vocal qualities. All the children were submitted to perceptual auditory analysis, acoustic vocal analysis, auditory acuity assessment (transient otoacoustic emissions and/or threshold tone audiometry), and videoendoscopic assessment (flexible laryngoscopy and rigid laryngoscopy). RESULTS: The groups were similar in age and gender. Parents reported a dysphonia rate of 76.6% in NOG and a vocal abuse rate of 68.3%. Eight children from NOG (13.34%) showed mild conductive hypoacusia. Laryngeal lesions were detected in 35 children from NOG (58%): inflammatory processes (n=19), mucosal thickening (n=10), nodules (n=5), and cyst (n=1). In children from the NOG were observed higher scores for the Grade, Roughness, Breathiness, Aesthenia, Strain, Instability (GRBAS) perceptual scale (P<0.05), lower maximum phonation time values, and higher values to the s/z ratio, insufficient nasal resonance. CONCLUSIONS: Relevant changes in perceptual auditory and acoustic vocal analyses and in the videolaryngoscopy were detected in children with nasal obstruction. These results showed the importance of the assessment of nasal obstruction in dysphonic children.