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α-Amylase inhibition is vital in controlling diabetic complications. Herein, we have synthesized a hybrid scaffold based on thiazole-chalcone to access α-amylase inhbition. The proposed structures were verified with spectroscopic techniques (UV-Vis., FT-IR, 1H-, 13C-NMR, and elemental analysis). The synthesized compounds were evaluated for their α-amylase and antioxidant potential. In vitro hemolytic assay was performed to test biocompatibility of all compounds. Among tested compounds, 4 c (IC50=3.8â µM), 4 g (IC50=14.5â µM), and 4 f (IC50=17.1â µM) were found excellent α-amylase inhibitors. However, none of the tested compounds exhibited significant antioxidant activity. All compounds showed less lysis than Triton X-100, but compounds 4 f and 4 h had the least lysis at all tested concentrations and were found to be safe for human erythrocytes. Molecular docking study was performed to evaluate the binding interactions of ligands with human pancreatic α-amylase (HPA). The binding score -8.09 to -8.507â kcal/mol revealed strong binding interactions in the ligand-protein complex. The docking results supplemented the observed α-amylase inhibition and hence augment the scaffold to serve as leads for the antidiabetic drug development.
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Diabetes is an emerging threat to the world due to large number of deaths reported within the last decade. To overcome its spread and complications, herein, we reported synthesis and anti-diabetic potential of twelve novel 2-[(arylidene)methylidene]hydrazinyl-1,3-thiazole-5-carbaldehydes (3a-l). All compounds have shown good to excellent α-amylase inhibition activity, among them ortho substituted analogues, the compound 3a (IC50= 14.6 mM) and 3l (IC50= 17.9 mM) showed excellent inhibition potential due to their strong electron donating nature of the substituents attached at the aryl ring. The compounds 3a to 3h (IC50= 6.70-10.80 ppm) exhibited excellent anti-glycation potential as compared to standard amino-guanidine (IC50= 11.92 ppm). Almost all the tested compounds are found biocompatible and very safe to the human erythrocyte cells at all tested concentrations. The molecular docking results have found that the binding energy score of all the tested compounds against human serum albumin protein (pdb: 1AO6) is between -5.1827 to -6.8661 kcal/mol far better than standard amino-guanidine (-4.234 kcal/mol).
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Objectives: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. METHODS: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. The study included patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for ≥3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. RESULTS: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinaemia and 70(42%) with hypreprolactinaemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Patients having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinaemia. CONCLUSIONS: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management.
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Hiperprolactinemia , Prolactina , Inhibidores de la Bomba de Protones , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversos , Femenino , Estudios Transversales , Masculino , Hiperprolactinemia/epidemiología , Hiperprolactinemia/inducido químicamente , Hiperprolactinemia/sangre , Hiperprolactinemia/tratamiento farmacológico , Prolactina/sangre , Adulto , Persona de Mediana Edad , Pakistán/epidemiología , PrevalenciaRESUMEN
In rural areas, land use decisions are not only shaped by economic considerations but also deeply influenced by cultural and social factors. The objective of this research is to examine the complex and diverse aspects of making decisions about how land is used in rural communities, specifically by investigating the influence of cultural and social elements. Using empirical data and rigorous analysis, this research examine how traditional practices, social norms, and community dynamics influence land use patterns. The research topic focuses on the need to have a thorough understanding of the fundamental elements that affect land use choices in rural regions, going beyond only economic incentives. This research objective is to address a significant vacuum in the current literature by examining the cultural and social aspects of land usage. This research provides vital insights for policymakers and stakeholders engaged in land management and rural development projects. This research utilizes a mixed-methods approach, using qualitative interviews, participatory observations, and quantitative surveys to collect comprehensive data on the cultural and socioeconomic elements that impact land use choices. The research sample includes a wide range of rural areas, guaranteeing a thorough representation of various cultural settings and socioeconomic backgrounds. Our study reveals that cultural traditions, social networks, and power structures have a substantial impact on land use practices in rural regions. Traditional land tenure systems, community ownership arrangements, and customary land-use practices play a vital role in influencing land-use choices and resource distribution within communities. The significance of these results is substantial for policymakers, land managers, and rural development practitioners. Policymakers may create land use policies and actions that are more appropriate to the specific cultural and socioeconomic environment by understanding the complex relationship between these aspects. Furthermore, promoting community involvement and allowing local actors to participate in decision-making may result in land management results that are both more sustainable and fair.
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Renewable energy is essential for boosting economic expansion and lowering carbon dioxide emission (CO2) to achieve carbon neutrality. This study's objective is to investigate the relationship between the use of renewable energy, economic growth, and CO2 for South Caucasus Countries. For analysis purposes, time series methods were applied on the panel data. Second-generation unit root and cointegration tests were used to test the cross-sectional dependence. Afterward, panel causality and panel VAR techniques were performed to examine the relationship between the variables. Based on feedback hypothesis, results of our causality analysis revealed a bidirectional causality relationship between growth and renewable energy consumption. Moreover, we revealed unidirectional causality from CO2 to renewable energy and from growth to CO2 emission. We also found that the effect of a shock in renewable energy on growth is increasing, and on CO2, it is decreasing implying that renewable energy consumption will trigger growth and have a reducing effect on CO2 emissions. We portrayed significant workable implications for policymakers, regulation bodies, companies, stakeholders, and managers. Results from this study should be extrapolated with caution since their applicability is limited to the South Caucasus Countries. In addition, the research heavily depends on summaries, which may obscure regional differences. In the future, researchers may want to dig deeper into the data and examine the subtle effect of renewable energy policy nationally. Moreover, including socio-economic aspects and technical improvements in the research might give a more thorough picture of the dynamics at play.
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Dióxido de Carbono , Desarrollo Económico , Energía Renovable , Dióxido de Carbono/análisisRESUMEN
The Green Economy Initiative aims to achieve economic development while minimizing carbon emissions by implementing a low-carbon economy across all sectors. It is noteworthy that ships play a significant role in global commodity transportation, accounting for approximately 80-90 percent. However, this also leads to a surge in fossil fuel consumption and alarming pollution levels. The data utilized in this article spans from 2010 to 2022 and specifically focuses on the shipping industry, drawing from information collected in 20 different provinces of China. Multiple panel regression models were constructed to analyze the influence of fiscal policies on facilitating the transition toward a low-carbon economy. In addition, a vector autoregression model was employed to examine the interconnected dynamics between low-carbon transition and budgetary guidelines. The findings indicate that tax-based policies demonstrate an inverted U-shaped relationship with low-carbon transition, whereas transfer payment policies exhibit an N-shaped pattern. The shipping sector is actively embracing low-carbon practices, largely due to incorporating digital technologies that mitigate the adverse impacts of fiscal regulations.
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In the current work, organic cyclopenta-thiophene (CPT) based derivatives (FICR and FICD1-FICD5) were designed by the modulation of end-capped acceptor group of the reference molecule i.e., FICR, to explore their nonlinear optical (NLO) response. The effect of terminal acceptor and donor groups in the tailored compounds was explored by using DFT based quantum calculations. The UV-Vis analysis, frontier molecular orbitals (FMOs), transition density matrix (TDM), natural bond orbitals (NBOs), density of states (DOS), nonlinear optical (NLO) analyses were performed at M06/6-311G(d,p) functional. The LUMO-HOMO band gaps of FICD1-FICD5 were found to be smaller (1.75-1.92 eV) comparative to FICR (1.98 eV). Moreover, the global reactivity parameters (GRPs) were correlated with the results of other analyses. FICD2 and FICD5 with lowest band gap 1.73 and 1.75 eV showed less hardness (0.86 and 0.87 eV, respectively), high softness (0.58 and 0.57 eV-1), and larger absorption spectrum (815 and 813 nm) in gaseous phase and (889 and 880 nm) in solvent phase among all entitled compounds. All the designed chromophores (FICD1-FICD5) demonstrated a significant NLO response as compared to FICR. Particularly, FICD2 and FICD5 exhibited the highest average linear polarizability (<α>) [2.86 × 10-22 and 2.88 × 10-22 esu], first hyperpolarizability (ßtot) (8.43 × 10-27 and 8.35 × 10-27 esu) and second hyperpolarizability (γtot) (13.20 × 10-32 and 13.0 × 10-32 esu) values as compared to the other derivatives. In nutshell, structural modeling of CPT based chromophores with extended acceptors, can be significantly utilized to achieve potential NLO materials.
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The current design codes i.e. AISC 360-16, CSA-S16-19, EC-04 etc. provide empirical relationships to estimate the capacity of shear connectors which were developed based on pushout tests of headed studs and channels connectors in exposed type sections. Therefore, these equations may result inaccurate predictions for strength of connectors in infilled-type sections. This study presents a detailed experimental study investigating the performance of angle connectors in composite sections. The testing program consisted two series of pushout tests. A total of 36 specimens were tested, considering the influence of several important parameters i.e. the length (Lc), height (hc), and web-thickness (tw) of angle connector, length of the weld (w) and the direction of shear connector (forward/backward) etc. The tests results demonstrated that with increasing connector height hs, and thickness, the maximum load Pmax and slip δu were increased. The connector direction didn't change much the load-slip behavior. The prediction accuracy of the existing shear capacity models was evaluated by comparing the predictions with experimental results. The current equations were noticed to be highly inconsistent in predicting the shear capacity of angle connectors, especially in case of infilled type sections. When the entire length of connector was taken as the effective length, the models overestimated the shear capacity. While in case when the welding length was taken as effective length in calculations, the models underestimated the shear strength of angle connectors.
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Aim: To synthesize novel more potent anti-diabetic agents. Methodology: A simple cost effective Hantzsch's synthetic strategy was used to synthesize 2-(2-arylidenehydrazinyl)thiazol-4(5H)-ones. Results: Fifteen new 2-(2-arylidenehydrazinyl)thiazol-4(5H)-ones were established to check their anti-diabetic potential. From alpha(α)-amylase inhibition, anti-glycation and anti-oxidant activities it is revealed that most of the compounds possess good anti-diabetic potential. All tested compounds were found to be more potent anti-diabetic agents via anti-glycation mode. The results of α-amylase and anti-oxidant inhibition revealed that compounds are less active against α-amylase and anti-oxidant assays. Conclusion: This study concludes that introduction of various electron withdrawing groups at the aryl ring and substitution of different functionalities around thiazolone nucleus could help to find out better anti-diabetic drug.
Diabetes is a most spreading chronicle disease effecting millions of peoples across the globe every year and this number increases day by day. To cure the human population from this dilemma, we had synthesized, characterized and evaluated the anti-diabetic behavior of our synthesized compounds. α-Amylase, in vitro anti-glycation and anti-oxidant assays were performed to find out good lead for Diabetes Mellitus. All tested compounds were found to be excellent anti-glycating agents with IC50 values far better than standard amino-guanidine (IC50 = 3.582 ± 0.002 µM). Compound 4m was most efficient glycation inhibitor (IC50 = 1.095 ± 0.002 µM). Cytotoxicity of all compounds was determined with in vitro hemolytic assay and found all compounds safe and bio-compatible to humans at all tested concentrations. The inhibition potential was also examined with theoretical docking studies to support our experimental results against human pancreatic alpha-amylase (HPA) and human serum albumin (HSA) proteins. All compounds showed excellent binding affinity with HSA active pockets however, only compound 4h and 4k binding affinity was good with HPA.
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Hipoglucemiantes , Simulación del Acoplamiento Molecular , Tiazoles , alfa-Amilasas , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/síntesis química , Tiazoles/química , Tiazoles/farmacología , Tiazoles/síntesis química , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Humanos , Relación Estructura-Actividad , Estructura MolecularRESUMEN
Introduction: Proton pump inhibitors (PPIs) are effective drugs used for multiple gastrointestinal complications. They are commonly used in both hospitalised and outpatients. However, little is known about its utilisation pattern in ambulatory patients. Aim: To evaluate the inexpedient continuous use of PPIs in patients with respect to treatment duration. Material and methods: A cross-sectional observational study was conducted from January 2018 to November 2019 in Khyber Pakhtunkhwa, Pakistan. Regular proton pump inhibitor users were identified through patient histories. Results: During the study period, 171 patients were included using a non-probability consecutive sampling technique, who were using regular proton pump inhibitors for a longer duration, i.e. from 3 months to 15 years. The highest proportion (42.8%) were using PPI regularly from 3 months to 1 year followed by 22.9% for 1-2 years, 12.0% for 2-3 years, 7.8% for 3-4 years, 4.2% for 4-5 years, and 10.24% for > 5 years. Omeprazole and esomeprazole were the most commonly used drugs, with 71.1% and 23.5% prevalence, respectively. A total of 33.73% of patients had continued PPI use on their own after initially being prescribed by the physician. Conclusions: It can be deduced that PPIs are used in outpatients beyond standard treatment guidelines. The inexpedient continuous use of proton pump inhibitors is of concern due to the risk of developing adverse effects. Therefore, patient counselling and periodic monitoring must be carried out to prevent the irrational use of PPIs.
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Aim: To synthesize novel more potent trypanocidal and leishmanicidal agents. Methods: Hantzsch's synthetic strategy was used to synthesize 1,3-thiazole-4-carboxylates and their N-benzylated derivatives. Results: 28 new thiazole-carboxylates and their N-benzylated derivatives were established to test their trypanocidal and leishmanicidal activities. From both series, compounds 3b, 4f, 4g, 4j and 4n exhibited a better or comparable trypanocidal profile to benznidazole. Among all tested compounds, 4n was found to be the most potent and was better than benznidazole. Conclusion: Further variation of substituents around 1,3-thiazole-4-carboxylates and or hydrazinyl moiety may assist in establishing better and more potent trypanocidal and leishmanicidal agents.
Chagas disease and leishmaniasis are neglected tropical diseases. Herein, 28 1,3-thiazoles have been synthesized from thiosemicarbazones in a rapid, efficient and cost-effective manner. In vitro assays were performed against intracellular amastigotes of Trypanosoma cruzi (T. cruzi) and promastigotes and intracellular amastigote forms of Leishmania infantum (L. infantum) and Leishmania amazonensis (L. amazonensis). Some of the 1,3-thiazole-4-carboxylates inhibited the amastigote form of T. cruzi without affecting macrophage viability, compound 4n being the most potent and better than benznidazole. Our synthesized compounds exhibited promising activity against T. cruzi, thus broadening options for scaffold and lead compound optimization. Concerning the leishmanicidal activity, compound 4g was the best prototype in terms of potency and selectivity. Compounds 4g and 3m showed moderate selectivity and potency against intracellular amastigotes of L. amazonensis and L. infantum, respectively.
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Nitroimidazoles , Tripanocidas , Trypanosoma cruzi , Tiazoles/farmacología , Ésteres/farmacología , Tripanocidas/farmacologíaRESUMEN
This study inspects the impact of environmental deterioration and income on longevity and fertility in Asian countries, specifically the nations that are highly vulnerable to extreme weather. The study examines the data, covering two decades from 2000 to 2019. The empirical conclusions of the panel ARDL-PMG and the CS-ARDL econometric models indicate that environmental degradation leads to a decline in birth rate and life expectancy, while a rising income has a significant influence over longevity. However, increasing per capita income alone cannot solve the problem of population crisis in climatically susceptible countries. Therefore, the sample countries must prioritize climate action and formulate climate-resilient policies to add more years to the lives of their citizens. Similarly, for increasing childbirth the sample nations need to make peace with nature. The outcomes of this study are strong enough, as both the models support each other's findings, producing similar significant outcomes.
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Objective: To evaluate the correlation of quantitative anti-dsDNA level with proteinuria levels in patients with lupus nephritis in a tertiary care hospital. Study design: In this prospective cross-sectional study, 76 patients of newly diagnosed SLE coming to Fatima Memorial Hospital were included in the study period between January 2020 to June 2020. Demographic data such as age, gender, lupus manifestations such as serositis, arthritis, mucocutaneous disease, and neuropsychiatric manifestations were recorded. Quantitative anti-dsDNA was measured by enzyme-linked immunosorbent assay and proteinuria was estimated by 24h urinary protein collection. Data was analyzed by SPSS 23. Association between categorical variables was assessed using chi-square test. For comparison of categorical independent and continuous dependent variable t-test or MannWhitney U test was applied. Results: The median age of the cohort was 29 (with inter quartile range IQR of 13) years. The female gender comprised of 68 (89.4%) of the cohort population. The median anti-dsDNA level was 54.9 (183.6 IQR) IU, and baseline proteinuria of the cohort was 520mg/dL (1.49 IQR). There was a significant association of anti-dsDNA level with systemic features such as arthritis (p=<0.01), serositis (p=<0.01) and, Raynaud's phenomenon (p=<0.01). NPSLE and mucocutaneous features did not show statistically significant association (p=0.91 and 0.14 respectively). Baseline anti-dsDNA showed a statistically significant correlation with baseline proteinuria levels (p=<0.01). Conclusion: Quantitative anti-dsDNA is directly correlated with nephritis measured as proteinuria, and can be detected even before organ involvement. Hence, it can determine disease course and guide early treatment.(AU)
Objetivo: Evaluar la correlación del nivel cuantitativo de anti-dsDNA con los niveles de proteinuria en pacientes con nefritis lúpica en un hospital de tercer nivel. Diseño del estudio: En este estudio transversal prospectivo se incluyeron 76 pacientes de LES recién diagnosticados que acudieron al Fatima Memorial Hospital en el período de estudio entre enero de 2020 y junio de 2020. Se registraron datos demográficos como edad, sexo, manifestaciones de lupus como serositis, artritis, enfermedad mucocutánea y manifestaciones neuropsiquiátricas. El anti-dsDNA cuantitativo se midió mediante un ensayo inmunoabsorbente ligado a enzimas y la proteinuria se estimó mediante la recogida de proteínas en orina de 24 horas. Los datos fueron analizados por SPSS 23. La asociación entre variables categóricas se evaluó mediante la prueba de χ2. Para la comparación de variable dependiente continua e independiente categórica se aplicó la prueba t o la prueba u de Mann Whitney. Resultados: La mediana de edad de la cohorte fue de 29 años (con rango intercuartil IQR de 13). El género femenino comprendía 68 (89,4%) de la población de la cohorte. El nivel medio de anti-dsDNA fue 54,9 (183,6 IQR) UI, y la proteinuria basal de la cohorte fue de 520mg/dL (1,49 IQR). Hubo una asociación significativa del nivel de anti-dsDNA con características sistémicas como artritis (p=<0,01), serositis (p=<0,01) y fenómeno de Raynaud (p=<0,01). El NPSLE y características mucocutáneas no mostraron asociación estadísticamente significativa (p=0,91 y 0,14, respectivamente). El anti-dsDNA basal mostró una correlación estadísticamente significativa con los niveles basales de proteinuria (p=<0,01). Conclusión: El anti-dsDNA cuantitativo se correlaciona directamente con la nefritis medida como proteinuria y puede detectarse incluso antes de la afectación de órganos; por lo tanto, puede determinar el curso de la enfermedad y orientar el tratamiento temprano.(AU)