Involvement of angiotensin II and beta-adrenergic receptors in the regulation of autophagy in human endothelial EA.hy926 cell line

Purpose: To investigate the role of angiotensin II (Ang II) and β adrenergic receptors (βARs) in autophagy regulation in human endothelial EA.hy926 cell line.Methods: The effect of pharmacological modulation of Ang II receptors and βARs on the expression of LC3B-II and p62 proteins (autophagosome formation marker and autophagic flux marker, respectively) in the human endothelial EA.hy926 cell line were investigated by immunoblotting technique.Results: Ang II-induced autophagy was characterized by increased LC3B-II and reduced p62 expressions. Candesartan, an AT1R agonist,  significantly suppressed the effects of Ang II, while a selective AT2R antagonist, PD123319, inhibited the effect of candesartan. An AT2R agonist, CGP-42112A, also suppressed the Ang II-induced autophagy. Treatment with isoproterenol enhanced the expression of LC3B-II and reduced that of p62; these effects were suppressed upon cotreatment with propranolol (non-selective βAR blocker propranolol). A selective β1AR agonist, dobutamine, reduced the expression of LC3B-II, and increased that of p62; the same was suppressed upon treatment with a selective β1AR antagonist, metoprolol. A selective β2AR agonist, salbutamol, resulted in increased expression of LC3B-II and reduced expression of p62. These effects were encountered upon treatment with selective β2AR antagonist, ICI-118,551.Conclusion: Based on the foregoing, it is evident that AT1Rs mediates Ang II-induced endothelial cell autophagy, while AT2Rs antagonizes the mechanism. βAR activation mediates isoproterenol-induced endothelial cell autophagy, which results from the balance of β1ARs-mediated suppression and β2ARsmediated upregulation of autophagy in the endothelial cells. Keywords: Autophagy, Angiotensin II type 1 receptors, Angiotensin II type 2 receptors β adrenergic type 1 receptors, β adrenergic type 2 receptors endothelial cell

Implications of advanced wastewater treatment: Electrocoagulation and electroflocculation of effluent discharged from a wastewater treatment plant

In this research, wastewater treatment was inspected on a pilot-scale wastewater treatment plant by electrochemical techniques, electrocoagulation (EC), electroflotation (EF) and electrophoretic deposition (EPD). The wastewater samples have been characterised by applying different parameters to determine optimum working conditions of the electrocoagulation reactor. Two electrodes have been tested separately with an outflow coming from primary and secondary sedimentation tank. The outflows from these tanks are introduced in EC reactor then EC reactor efficacy is determined for the removal of chemical oxygen demand (COD), suspended solids, micropollutants and amount of coagulants in agglomerates at different current densities. The amounts of suspended solids (SS) in influent and effluent streams were determined by the membrane filtration technique. The operational applied current values range from 1–4 A in the case of COD removal by Fe and Al. While for SS aggregation the applied current ranges from 0.5–3 A and inflow rate was tested from 250 to 500 L/h. The pH of outflows increased by increasing applied current and both of these parameters were found a positive increase in the amount of SS aggregations after EC treatment. Furthermore, the COD removal efficiency was found to be 56–57 % and 12–18 % in case Fe and Al electrode respectively after EC treatment. The results showed that applied current is the most effective parameter, whereas the aluminium electrodes have produced more amounts of flocs and bubbles in comparison to iron electrodes at similar amount of current density

Goal model integration for tailoring product line development processes

Many companies rely on the promised benefits of product lines, targeting systems between fully custom made software and mass products. Such customized mass products account for a large number of applications automatically derived from a product line. This results in the special importance of product lines for companies with a large part of their product portfolio based on their product line. The success of product line development efforts is highly dependent on tailoring the development process. This paper presents an integrative model of influence factors to tailor product line development processes according to different project needs, organizational goals, individual goals of the developers or constraints of the environment. This model integrates goal models, SPEM models and requirements to tailor development processes

Standardized Extract of Bacopa monniera

The aim of the present study is to investigate the effect of standardized extract of Bacopa monnieri (memory enhancer) and Melatonin (an antioxidant) on nuclear factor erythroid 2 related factor 2 (Nrf2) pathway in Okadaic acid induced memory impaired rats. OKA (200 ng) was administered intracerebroventricularly (ICV) to induce memory impairment in rats. Bacopa monnieri (BM-40 and 80 mg/kg) and Melatonin (20 mg/kg) were administered 1 hr before OKA injection and continued daily up to day 13. Memory functions were assessed by Morris water maze test on days 13–15. Rats were sacrificed for biochemical estimations of oxidative stress, neuroinflammation, apoptosis, and molecular studies of Nrf2, HO1, and GCLC expressions in cerebral cortex and hippocampus brain regions. OKA caused a significant memory deficit with oxidative stress, neuroinflammation, and neuronal loss which was concomitant with attenuated expression of Nrf2, HO1, and GCLC. Treatment with BM and Melatonin significantly improved memory dysfunction in OKA rats as shown by decreased latency time and path length. The treatments also restored Nrf2, HO1, and GCLC expressions and decreased oxidative stress, neuroinflammation, and neuronal loss. Thus strengthening the endogenous defense through Nrf2 modulation plays a key role in the protective effect of BM and Melatonin in OKA induced memory impairment in rats

Autophagy inhibition by chloroquine prevents increase in blood pressure and preserves endothelial functions

Purpose: To determine the effects of lysosomal inhibition of autophagy by chloroquine (CHQ) onhypertension-associated changes in the endothelial functions. Method: Angiotensin II (Ang II)-treated human endothelial cell line EA.hy926 and renovascularhypertensive rats were subjected to CHQ treatment (in vitro: 0.5, 1, and 2.5 μM; in vivo: 50 mg/kg/dayfor three weeks). Changes in the protein expressions of LC3b II (autophagosome formation marker) andp62 (autophagy flux marker) were assessed using immunoblotting. Cell migration assay, tubuleformation assay (in vitro), and organ bath studies (in vivo) were performed to evaluate the endothelialfunctions. Hemodynamic parameters were measured as well. Results: A higher expression of LC3b II and a reduced expression of p62 observed in the Ang II-treatedendothelial cells, as well as in the aorta of the hypertensive rats, indicated enhanced autophagy.Treatment with CHQ resulted in reduced autophagy flux (in vitro as well as in vivo) and suppressed AngII-induced endothelial cell migration and angiogenesis (in vitro). The treatment with CHQ was alsoobserved to prevent increase in blood pressure in hypertensive rats and preserved acetylcholineinducedrelaxation in phenylephrine-contracted aorta from the hypertensive rats. In addition, chloroquineattenuated Ang II-induced contractions in the aorta of normotensive as well as hypertensive rats. Conclusion: These observations indicated that CHQ lowers the blood pressure and preserves thevascular endothelial function during hypertension. Keywords: Angiotensin II, Autophagy, Chloroquine, Endothelial function, Hypertension, Vasculardysfunctio

Histomorphometric effects of Raphanus Sativus leaf ex-tract on Carbon Tetrachloride induced hepatotoxicity.

Introduction: Carbon tetrachloride (CCl4) adversely affect the structural/ and or functional properties of the hepatic tissue, leading to grave implica-tions. Currently plant-based compounds have gained sufficient space in the treatment of liver diseases. Among such plants is Raphanus sativus, a cru-ciferous plant also commonly called Radish, which has since long been used in traditional medicine.Objective: To evaluate the protective role of Raphanus sativus in CCl4-induced hepatotoxicity through assessment of liver function and oxidative stress markers in albino Wistar rats.Methodology: This Quasi-experimental study was conducted between Sep-tember 2019 to March 2020 at the Postgraduate Research Laboratory Isra University, Hyderabad. Albino Wistar selected by non-random purposive sampling were divided equally into three different groups: Group A (control group), Group B (CCl4 experimental group), and Group C (CCl4 plus Raphanus sativus group). Blood samples were collected through cardiac puncture followed by hepatic histopathological analysis using light micro-scope. Data was analyzed using SPSS version 24, with ANOVA and Post hoc Tukey’s analysis used for comparison of different study variables.Results: Statistically significant rise relative liver weight of group B rats compared with the group A and C rats (P <0.05). Moreover, statistically sig-nificant (P <0.05) rise in serum markers of hepatic functions was observed after CCl4 administration in Group B. Treatment with Raphanus Sativus ad-ministration significantly reduced serum levels of LFTs (p<0.05). There was a significant decline in the plasma levels of oxidative markers in group B while marked histopathological changes like necrosis, sinusoidal dilatation and congestion observed among animals of group B.Conclusion: Raphanus Sativus exerts an anti-oxidative, and hepato-protective effect against CCl4-induced hepatic tissue damage.Keywords: CCl4, Hepato-protective, Raphanus Sativus

Fractional optimal control analysis of Covid-19 and dengue fever co-infection model with Atangana-Baleanu derivative

A co-infection with Covid-19 and dengue fever has had worse outcomes due to high mortality rates and longer stays either in isolation or at hospitals. This poses a great threat to a country's economy. To effectively deal with these threats, comprehensive approaches to prevent and control Covid-19/dengue fever co-infections are desperately needed. Thus, our focus is to formulate a new co-infection fractional model with the Atangana-Baleanu derivative to suggest effective and feasible approaches to restrict the spread of co-infection. In the first part of this paper, we present Covid-19 and dengue fever sub-models, as well as the co-infection model that is locally asymptotically stable when the respective reproduction numbers are less than unity. We establish the existence and uniqueness results for the solutions of the co-infection model. We extend the model to include a vaccination compartment for the Covid-19 vaccine to susceptible individuals and a treatment compartment to treat dengue-infected individuals as optimal control strategies for disease control. We outline the fundamental requirements for the fractional optimal control problem and illustrate the optimality system for the co-infection model using Pontraygin's principle. We implement the Toufik-Atangana approximating scheme to simulate the optimality system. The simulations show the effectiveness of the implemented strategy in determining optimal vaccination and treatment rates that decrease the cost functional to a minimum, thus significantly decreasing the number of infected humans and vectors. Additionally, we visualize a meaningful decrease in infection cases with an increase in the memory index. The findings of this study will provide reasonable disease control suggestions to regions facing Covid-19 and dengue fever co-infection

Effects of Allium sativum in cardiovascular diseases: A Review

Epidemiologic studies show an inverse correlation between garlic consumption and progression of cardiovascular disease. Cardiovascular disease is associated with multiple factors such as raised serum total cholesterol, raised LDL and an increase in LDL oxidation, increased platelet aggregation, hypertension, and smoking. Numerous in vitro studies have confirmed the ability of garlic to reduce these parameters. Thus, garlic has been shown to inhibit enzymes involved in lipid synthesis, decrease platelet aggregation, prevent lipid peroxidation of oxidized erythrocytes and LDL, increase antioxidant status, and inhibit angiotensin-converting enzyme. These findings have also been addressed in clinical trials. The studies point to the fact that garlic reduces cholesterol, inhibits platelet aggregation, reduces blood pressure, and increases antioxidant status. Since 1993, 44% of clinical trials have indicated a reduction in total cholesterol, and the most profound effect has been observed in garlic's ability to reduce the ability of platelets to aggregate. Mixed results have been obtained in the area of blood pressure and oxidative-stress reduction. The findings are limited because very few trials have addressed these issues. The negative results obtained in some clinical trials may also have resulted from usage of different garlic preparations, unknown active constituents and their bioavailability, inadequate randomization, selection of inappropriate subjects, and short duration of trials. This review analyzes in vitro and in vivo studies published since 1993 and concludes that although garlic appears to hold promise in reducing parameters associated with cardiovascular disease, more in-depth and appropriate studies are required. Keywords: Allium sativum, hypercholesterolemia, antioxidants, cardioprotective, HMG-CoA reductase

Predator- Prey Interaction In Plant –Associated Ecosystems. Effect On Plant Fitness And Trophic Cascade

Predator-prey interactions in plant-associated ecosystems play a crucial role in shaping ecosystem dynamics and stability. This study provides a comprehensive overview of the implications of these interactions, highlighting the intricate web of relationships among predators, herbivores, and plants. The findings underscore the importance of maintaining predator-prey interactions for ecosystem stability and functioning. Trophic cascades initiated by predator-prey interactions have been shown to regulate herbivore populations, indirectly benefiting plant communities. However, human activities can significantly impact predator populations and trophic cascades, emphasizing the need for conservation efforts to preserve these important ecological dynamics. The integration of molecular techniques and modeling approaches can enhance our understanding of trophic cascades in plant-associated ecosystems. Conservation strategies aimed at promoting predator diversity and enhancing plant fitness are essential for maintaining ecosystem stability and promoting sustainable management of plant-associated ecosystems. Further research is needed to investigate the complex dynamics of predator-prey interactions and trophic cascades, as well as to develop effective conservation strategies to preserve these important ecological dynamics