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1.
Sensors (Basel) ; 24(11)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38894079

RESUMO

This survey paper explores advanced nonlinear control strategies for Unmanned Aerial Vehicles (UAVs), including systems such as the Twin Rotor MIMO system (TRMS) and quadrotors. UAVs, with their high nonlinearity and significant coupling effects, serve as crucial benchmarks for testing control algorithms. Integration of sophisticated sensors enhances UAV versatility, making traditional linear control techniques less effective. Advanced nonlinear strategies, including sensor-based adaptive controls and AI, are increasingly essential. Recent years have seen the development of diverse sliding surface-based, sensor-driven, and hybrid control strategies for UAVs, offering superior performance over linear methods. This paper reviews the significance of these strategies, emphasizing their role in addressing UAV complexities and outlining future research directions.

2.
Sensors (Basel) ; 24(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38610310

RESUMO

Smart cities are powered by several new technologies to enhance connectivity between devices and develop a network of connected objects which can lead to many smart industrial applications. This network known as the Industrial Internet of Things (IIoT) consists of sensor nodes that have limited computing capacity and are sometimes not able to execute intricate industrial tasks within their stipulated time frame. For faster execution, these tasks are offloaded to nearby fog nodes. Internet access and the diverse nature of network types make IIoT nodes vulnerable and are under serious malicious attacks. Malicious attacks can cause anomalies in the IIoT network by overloading complex tasks, which can compromise the fog processing capabilities. This results in an increased delay of task computation for trustworthy nodes. To improve the task execution capability of the fog computing node, it is important to avoid complex offloaded tasks due to malicious attacks. However, even after avoiding the malicious tasks, if the offloaded tasks are too complex for the fog node to execute, then the fog nodes may struggle to process all legitimate tasks within their stipulated time frame. To address these challenges, the Trust-based Efficient Execution of Offloaded IIoT Trusted tasks (EEOIT) is proposed for fog nodes. EEOIT proposes a mechanism to detect malicious nodes as well as manage the allocation of computing resources so that IIoT tasks can be completed in the specified time frame. Simulation results demonstrate that EEOIT outperforms other techniques in the literature in an IIoT setting with different task densities. Another significant feature of the proposed EEOIT technique is that it enhances the computation of trustable tasks in the network. The results show that EEOIT entertains more legitimate nodes in executing their offloaded tasks with more executed data, with reduced time and with increased mean trust values as compared to other schemes.

3.
Pak J Med Sci ; 38(3Part-I): 589-594, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480532

RESUMO

Objectives: Rasagiline, a drug for Parkinson's disease is metabolized by CYP1A2 enzyme. The objective of the study was to investigate the influence of cytochrome P450 1A2 variants and smoking status of healthy individuals on the pharmacokinetics of rasagiline. Methods: A comparative, open label, interventional, single oral dose, pharmacokinetic study was performed on 108 healthy volunteers in UHS & UVAS, Lahore. Data collection was initiated in June 2016 and ended in January 2018. It was divided in three phases with 1, 2 and 5mg of rasagiline given to a group of 36 volunteers in each phase. Volunteers were sub-divided into six groups of AA smokers, AA non-smokers, AC smokers, AC non-smokers, CC smokers & CC non-smokers on the basis of genotyping and smoking status. Serial blood sampling was performed at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 & 12 hours after administration of rasagiline tablets. Plasma concentrations were determined using High Performance Liquid Chromatography (HPLC) method. Pharmacokinetic (PK) parameters were calculated using software (APO) pharmacological analysis. Results: Analysis of variance (ANOVA) showed significant difference between AA and CC groups. Multiple group comparison with post hoc Tukey's revealed that AA-smokers had significantly less tmax (p<0.001), t1/2 (p<0.012), AUC (p<0.008) and highest Cl (p<0.001) as compared to CC-smokers. The trend was same across all three doses. Conclusion: The study concludes that the systemic metabolism of rasagiline is significantly increased in CYP1A2*AA variants while smoking status did not show consistent difference in PK parameters.

4.
Sensors (Basel) ; 20(7)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32244668

RESUMO

Internet of Things (IoT) is a promising technology that uses wireless sensor networks to enable data collection, monitoring, and transmission from the physical devices to the Internet. Due to its potential large scale usage, efficient routing and Medium Access Control (MAC) techniques are vital to meet various application requirements. Most of the IoT applications need low data rate and low powered wireless transmissions and IEEE 802.15.4 standard is mostly used in this regard which offers superframe structure at the MAC layer. However, for IoT applications where nodes have adaptive data traffic, the standard has some limitations such as bandwidth wastage and latency. In this paper, a new superframe structure is proposed that is backward compatible with the existing parameters of the standard. The proposed superframe overcomes limitations of the standard by fine-tuning its superframe structure and squeezing the size of its contention-free slots. Thus, the proposed superframe adjusts its duty cycle according to the traffic requirements and accommodates more nodes in a superframe structure. The analytical results show that our proposed superframe structure has almost 50% less delay, accommodate more nodes and has better link utilization in a superframe as compared to the IEEE 802.15.4 standard.

6.
Pak J Med Sci ; 32(4): 917-21, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27648039

RESUMO

OBJECTIVES: To see the early post-operative outcomes of off-pump versus on-pump coronary artery bypass graft surgery. METHODS: This retrospective analytical study was conducted at Ch. Pervaiz Elahi Institute of Cardiology Multan, Pakistan. Our Primary outcome variables were; necessity of inotropic support, nonfatal myocardial infarction, ICU stay, nonfatal stroke, new renal failure requiring dialysis and death within 30 days after operation. There were two groups of patients; Group-I (On-pump group) and Group-II (Off-pump Group). SPSS V17 was used for data analysis. Independent sample t-test and Mann Whitney U test were used to compare quantitative Variables. Chi-square test and Fisher's exact test were used to analyze qualitative variables. P-value ≤ 0.05 was considered significant. RESULTS: Three hundred patients were included in this study. There were no significant difference regarding risk factors except hyper-cholestrolemia which was high in off pump group (p-value 0.05). Angiographic and Echocardiographic characteristics e.g. preoperative ejection fraction, LV function grade and severity of CAD was same between the groups. Mortality risk scores and Priority status for surgery were also same. Regarding post-operative outcomes; Post-op CKMB Levels, need and duration of inotropic support, mechanical ventilation time and ICU stay was significantly less in Off-Pump group (p-value 0.001, <0.0001, 0.006, 0.025 and 0.001 resp.). Peri-operative chest drainage was significantly high in On-pump CABG group (p-value 0.027). Incidence of post-op complications was not statistically different between the groups. CONCLUSIONS: At 30 days follow-up, Incidence of myocardial infarction, necessity and duration of inotropic support, ICU stay period and peri-operative bleeding were significantly less in off-pump group. The incidence of neurologic, pulmonary and renal complications was same between the off-pump and on-pump groups.

7.
Pak J Med Sci ; 31(6): 1318-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26870089

RESUMO

BACKGROUND AND OBJECTIVES: Modified Bentall procedure has become a gold standard in the treatment of combined aortic root and aortic valve diseases. Bleeding is an important predictor of morbidity and mortality after the Bentall operation. Our objective was to evaluate the early outcomes of Modified Button-Bentall procedure with cuff technique for aortic root replacement surgery regarding hemostasis. METHODS: A total number of 32 patients who underwent elective Bentall operation from January 2008 to December 2014 were included in the study. In 18 patients (Group I) modified Button-Bentall procedure with formation of cuff was used and in 14 patients (Group II) Modified Button technique without cuff formation was used for aortic root replacement. Data was analyzed using SPSS V16. Chi-square test, Fisher's Exact test and independent sample t-test was used to analyze Qualitative and Quantitative variables. RESULTS: Three patients in Group II and two patients in group I was in congestive cardiac failure pre-operatively. Out of thirty two patients two patients were having Aortic root dissection one in each group. Total bypass time and cross-clamp time were significantly high in Group I. There was no significant difference regarding duration of inotropic support, ventilation time, ICU stay and hospital stay time in patients of Group I and Group II. But post-op Chest drainage was very high in Group II 1158+451.25 ml versus 488.89+168.27 ml in group I (p-value <0.0001). There was one in hospital death in Group II. CONCLUSIONS: Formation of cuff of remnant of aorta during proximal anastomosis results in significant reduction in post-operative bleeding and was better in hospital outcomes.

8.
ISA Trans ; 146: 308-318, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38199841

RESUMO

This paper proposes an extended state observer (ESO) based data-driven set-point learning control (DDSPLC) scheme for a class of nonlinear batch processes with a priori P-type feedback control structure subject to nonrepetitive uncertainties, by only using the process input and output data available in practice. Firstly, the unknown process dynamics is equivalently transformed into an iterative dynamic linearization data model (IDLDM) with a residual term. A radial basis function neural network is adopted to estimate the pseudo partial derivative information related to IDLDM, and meanwhile, a data-driven iterative ESO is constructed to estimate the unknown residual term along the batch direction. Then, an adaptive set-point learning control law is designed to merely regulate the set-point command of the closed-loop control structure for realizing batch optimization. Robust convergence of the output tracking error along the batch direction is rigorously analyzed by using the contraction mapping approach and mathematical induction. Finally, two illustrative examples from the literature are used to validate the effectiveness and advantage of the proposed design.

9.
Am J Trop Med Hyg ; 110(5): 921-924, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38579702

RESUMO

Malaria elimination is one of the top health care priorities in India, necessitating accessible and accurate diagnosis for effective treatment. A malaria slide bank in India is a collection of quality-controlled malaria-positive and -negative slides and is considered a vital asset for quality diagnosis. The collection of blood samples, preparation of blood smears, staining, quality control, molecular characterizations, and slide validation were carried out according to standard operating procedures in accordance with the WHO reference laboratory. The true count and parasite density per microliter were computed in accordance with WHO guidelines. Over 27 months, 48 batches (8,196 slides) were prepared. Overall, the majority of slide batches were Plasmodium vivax (45.9%; 22/48), followed by Plasmodium falciparum (25%; 12/48), malaria-negative infections (25%; 12/48), and mixed infections (4.1%; 2/48). All 48 batches passed internal validation by WHO-certified level-1 microscopists. For a batch, the true count was the median of the validators' counts (range, 111-280,795 parasites/µL). Except for mixed infections, the PCR results agreed with the verified microscopy results. Malaria slide bank slides would be a valuable tool for quality control, assurance, and microscopist training.


Assuntos
Microscopia , Plasmodium vivax , Controle de Qualidade , Índia/epidemiologia , Humanos , Microscopia/métodos , Microscopia/normas , Plasmodium vivax/isolamento & purificação , Malária Vivax/diagnóstico , Malária Vivax/epidemiologia , Malária Falciparum/diagnóstico , Malária Falciparum/epidemiologia , Malária/diagnóstico , Malária/epidemiologia , Plasmodium falciparum/isolamento & purificação , Plasmodium falciparum/genética , Bancos de Espécimes Biológicos
10.
PLoS One ; 19(4): e0298363, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578775

RESUMO

Smart cities provide ease in lifestyle to their community members with the help of Information and Communication Technology (ICT). It provides better water, waste and energy management, enhances the security and safety of its citizens and offers better health facilities. Most of these applications are based on IoT-based sensor networks, that are deployed in different areas of applications according to their demand. Due to limited processing capabilities, sensor nodes cannot process multiple tasks simultaneously and need to offload some of their tasks to remotely placed cloud servers, which may cause delays. To reduce the delay, computing nodes are placed in different vicinitys acting as fog-computing nodes are used, to execute the offloaded tasks. It has been observed that the offloaded tasks are not uniformly received by fog computing nodes and some fog nodes may receive more tasks as some may receive less number of tasks. This may cause an increase in overall task execution time. Furthermore, these tasks comprise different priority levels and must be executed before their deadline. In this work, an Efficient Offloaded Task Execution for Fog enabled Smart cities (EOTE - FSC) is proposed. EOTE - FSC proposes a load balancing mechanism by modifying the greedy algorithm to efficiently distribute the offloaded tasks to its attached fog nodes to reduce the overall task execution time. This results in the successful execution of most of the tasks within their deadline. In addition, EOTE - FSC modifies the task sequencing with a deadline algorithm for the fog node to optimally execute the offloaded tasks in such a way that most of the high-priority tasks are entertained. The load balancing results of EOTE - FSC are compared with state-of-the-art well-known Round Robin, Greedy, Round Robin with longest job first, and Round Robin with shortest job first algorithms. However, fog computing results of EOTE - FSC are compared with the First Come First Serve algorithm. The results show that the EOTE - FSC effectively offloaded the tasks on fog nodes and the maximum load on the fog computing nodes is reduced up to 29%, 27.3%, 23%, and 24.4% as compared to Round Robin, Greedy, Round Robin with LJF and Round Robin with SJF algorithms respectively. However, task execution in the proposed EOTE - FSC executes a maximum number of offloaded high-priority tasks as compared to the FCFS algorithm within the same computing capacity of fog nodes.


Assuntos
Algoritmos , Comunicação , Cidades , Instalações de Saúde , Ciência da Informação
11.
MethodsX ; 10: 102035, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36798835

RESUMO

In this paper, the boundary layer flow of viscous incompressible fluid over an inclined stretching plate in porous media with body force and heat transfer has been studied. To solve this problem, we develop a suitable spline method which is used to calculate the velocity function of the flow problem. We proceed as follows:•With a suitable stream function, the concerned boundary layer equation is converted into non-linear third order ordinary differential equation together with appropriate boundary conditions in an infinite domain which has been further linearized by using quasi-linearization method.•Then, we develop a non polynomial quintic spline technique which has been used to find the numerical values of the velocity function of the flow problem. The convergence analysis of the developed spline technique has been discussed.•Later, the method developed so far has been applied to solve nonlinear boundary value problem for different angles of inclination and Froude number. The values obtained so far have been used to study heat flow problem. Finally, skin friction has been discussed.

12.
Future Sci OA ; 9(5): FSO862, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37180609

RESUMO

The drug discovery and development (DDD) process in pursuit of novel drug candidates is a challenging procedure requiring lots of time and resources. Therefore, computer-aided drug design (CADD) methodologies are used extensively to promote proficiency in drug development in a systematic and time-effective manner. The point in reference is SARS-CoV-2 which has emerged as a global pandemic. In the absence of any confirmed drug moiety to treat the infection, the science fraternity adopted hit and trial methods to come up with a lead drug compound. This article is an overview of the virtual methodologies, which assist in finding novel hits and help in the progression of drug development in a short period with a specific medicinal solution.


An extensive survey of technological applications in drug discovery and development, encompassing offline and online approaches, is presented in this review. The span of research issues that can be tackled using these advances is vast, opening new horizons for future innovations. The article is designed to incite further research investments into drug development procedures and bridge existing research voids by outlining multiple pharmaceutical products that resulted from employing systematic computational methodologies.

13.
Micromachines (Basel) ; 14(9)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37763923

RESUMO

The evaporation of liquid hydrocarbon n-heptane is discussed in detail with experimentation and numerical techniques. A maximum wall temperature of 1050 K was reported during an experimental process with a two-phase flow that was stable and had a prominent meniscus at a small fuel flow rate (FFR) ≤ 10 µL/min. At medium to high FFR (30-70 µL/min), the flow field was unstable, with nucleating bubbles and liquid droplets inside the microtube and the maximum temperature recorded was 850 K for 70 µL/min. For the numerical model, the temperature of the wall was used as a boundary condition. Using the numerical model, the evaporative flux at the meniscus, pressure drop, pressure oscillation, and heat transfer coefficient (HTC) were investigated. A single peak in HTC was obtained at a low fuel flow rate, while multiple peaks were obtained for high FFR. At low FFR, the pressure peak was observed to be 102.4 KPa, whereas at high FFR, the pressure peak increased to 105.5 KPa. This shows a 2% increase in pressure peak with an increase in FFR. Similarly, when the FFR increased from 5 µL/min to 70 µL/min, the pressure drop increased from 500 Pa to 2800 Pa. The high amplitude of pressure drops and a high peak of HTC were found, which depend on the mass flow rate. The coefficient of variation for pressure drop depends mainly on the fuel flow rate.

14.
Micromachines (Basel) ; 14(7)2023 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-37512786

RESUMO

Microelectronic components are used in a variety of applications that range from processing units to smart devices. These components are prone to malfunctions at high temperatures exceeding 373 K in the form of heat dissipation. To resolve this issue, in microelectronic components, a cooling system is required. This issue can be better dealt with by using a combination of metal foam, heat sinks, and nanofluids. This study investigates the effect of using a rectangular-finned heat sink integrated with metal foam between the fins, and different water-based nanofluids as the working fluid for cooling purposes. A 3D numerical model of the metal foam with a BCC-unit cell structure is used. Various parameters are analyzed: temperature, pressure drop, overall heat transfer coefficient, Nusselt number, and flow rate. Fluid flows through the metal foam in a turbulent flow with a Reynold's number ranging from 2100 to 6500. The optimum fin height, thickness, spacing, and base thickness for the heat sink are analyzed, and for the metal foam, the material, porosity, and pore density are investigated. In addition, the volume fraction, nanoparticle material, and flow rate for the nanofluid is obtained. The results showed that the use of metal foam enhanced the thermal performance of the heat sink, and nanofluids provided better thermal management than pure water. For both cases, a higher Nusselt number, overall heat transfer coefficient, and better temperature reduction is achieved. CuO nanofluid and high-porosity low-pore-density metal foam provided the optimum results, namely a base temperature of 314 K, compared to 341 K, with a pressure drop of 130 Pa. A trade-off was achieved between the temperature reduction and pumping power, as higher concentrations of nanofluid provided better thermal management and resulted in a large pressure drop.

15.
J Nanosci Nanotechnol ; 12(9): 7167-72, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23035448

RESUMO

We present an analytical treatment of diffusional release of a dispersed solute from a cylindrical non-erodible polymeric matrix and study the mechanism of diffusional release of solute from the matrix system as a function of solute loading parameter. The diffusion equation is solved exactly under perfect sink condition for certain concentration of solute in the form of cylindrical geometry. The numerical solution of diffusional release function as a function of time is found to be increased initially and then remain constant after certain time, tau(c). This tac(c) is found to be as a function of solute loading parameter. The asymptotic solutions of the diffusional release function is also presented.

16.
Molecules ; 17(5): 5050-61, 2012 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-22555295

RESUMO

An efficient method was developed for plant regeneration and establishment from alginate encapsulated synthetic seeds of Rauvolfia serpentina. Synthetic seeds were produced using in vitro proliferated microshoots upon complexation of 3% sodium alginate prepared in Llyod and McCown woody plant medium (WPM) and 100 mM calcium chloride. Re-growth ability of encapsulated nodal segments was evaluated after storage at 4 °C for 0, 1, 2, 4, 6 and 8 weeks and compared with non-encapsulated buds. Effects of different media viz; Murashige and Skoog medium; Lloyd and McCown woody Plant medium, Gamborg's B5 medium and Schenk and Hildebrandt medium was also investigated for conversion into plantlets. The maximum frequency of conversion into plantlets from encapsulated nodal segments stored at 4 °C for 4 weeks was achieved on woody plant medium supplement with 5.0 µM BA and 1.0 µM NAA. Rooting in plantlets was achieved in half-strength Murashige and Skoog liquid medium containing 0.5 µM indole-3-acetic acid (IAA) on filter paper bridges. Plantlets obtained from stored synseeds were hardened, established successfully ex vitro and were morphologically similar to each other as well as their mother plant. The genetic fidelity of Rauvolfia clones raised from synthetic seeds following four weeks of storage at 4 °C were assessed by using random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) markers. All the RAPD and ISSR profiles from generated plantlets were monomorphic and comparable to the mother plant, which confirms the genetic stability among the clones. This synseed protocol could be useful for establishing a particular system for conservation, short-term storage and production of genetically identical and stable plants before it is released for commercial purposes.


Assuntos
DNA de Plantas/análise , Repetições de Microssatélites/genética , Rauwolfia/genética , Sementes/genética , Alginatos , Cloreto de Cálcio , Meios de Cultura , Ácido Glucurônico , Ácidos Hexurônicos , Ácidos Indolacéticos/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Brotos de Planta/fisiologia , Técnica de Amplificação ao Acaso de DNA Polimórfico , Rauwolfia/crescimento & desenvolvimento , Recuperação de Função Fisiológica , Refrigeração , Sementes/crescimento & desenvolvimento
17.
J Pak Med Assoc ; 62(5): 426-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22755302

RESUMO

OBJECTIVES: To assess the prevalence of self medication among Pakistanis in rural and urban settings. METHODS: A door-to-door survey was carried out during June and July 2008 and 2009 after due verbal consent taken from the residents. The houses were randomly selected from ultra posh area, quarters of government employees, residents of Barani Training Institute, low socio-economic population in the surrounding of Adiallah road near Rawalpindi, and a remote village Raye Chak, (population 5000) some 50 kilometers away from the city. RESULTS: There were 2042 dosage forms of drugs from 430 houses; allopathic medicine 89.3%; traditional medicines 6.7%; and homeopathic drugs 4% representation. The top 10 companies had more than 57% market share among 147 firms whose products were reported. The availability of paediatric drugs mixtures/syrups was 24%, and injectiables, 5.5%. Nonsteroidal anti-inflammatory drugs (NSAID) had 38% representation; antimicrobials 25%, multivitamins and haematinics were 1.6% that was contrary to the general perception of the irrational use of this group of medicines. CONCLUSION: Alternative medicine is gaining ground. Overuse of anti-inflammatory drugs suggest higher prevalence of pain, inflammation and infections than systemic disorders in society.


Assuntos
Terapias Complementares/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Paquistão , Farmacoepidemiologia , Automedicação/estatística & dados numéricos , Classe Social , Inquéritos e Questionários
18.
Physiol Mol Biol Plants ; 18(4): 381-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24082502

RESUMO

A comparative performance of two explants types (CN and Nodal) for their efficiency to induce multiple shoot regeneration in Clitoria ternatea has been carried out. Thidiazuron (TDZ) in different concentrations (0.05-2.5 µM) was used as a supplement to the Murashige and Skoog's (MS) basal media. Explant type apart, two factors viz. concentration and exposure duration to TDZ played an important role in affecting multiple shoot regeneration. Cotyledonary node explants produced the best results at 0.1 µM TDZ, while in nodal explants the highest rate of shoot formation was achieved on MS medium supplemented with 1.0 µM TDZ. In both the explants, shoot multiplication increased when the regenerated shoots were subcultured on hormone free MS medium after 4 weeks of exposure to TDZ. Among the two, cotyledonary node explants produced considerably higher number of shoots at a comparatively lower concentration of TDZ than nodal explants. The regenerated shoots rooted best on MS medium containing 1.0 µM indole-3-butyric acid (IBA) and were successfully established in pots containing garden soil with 88 % survival rate. All the regenerated plants showed normal morphology and growth characteristics.

19.
Plants (Basel) ; 11(9)2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35567164

RESUMO

An improved and stable micropropagation system using the cytokinin, meta-Topolin (N6 (3-hydroxybenzylamino purine-mT), with nodal explants in Lagerstroemia speciosa L. was established. Among the different doses of mT, the maximum number of shoots with the highest shoot length was obtained using Murashige and Skoog's (MS) medium supplemented with 5.0 µM mT. The results were consistent throughout the proliferation period, when recorded at week 4, 8, and 12 of being cultured, with an average of 16.4 shoots per nodal explant, and having a mean length of 4.10 cm at week 8. Shoot proliferation rates could be further improved by a combination of 5.0 µM mT with 0.5 µM α-naphthalene acetic acid in MS medium; nodal explants produced an average of 24.3 shoots with a mean length of 5.74 cm after 8 weeks of being cultured. Among the five different concentrations of three auxins tested for the rooting of microshoots in MS medium, a 1.0 µM indole-3-butyric acid treatment was the best, with an average of 10.3 roots per microshoot at an average length of 3.56 cm in 93% of microshoots within 4 weeks of being transferred to this medium. A significant reduction of both chlorophyll a and b in leaves during the first week of acclimation corresponded with a high accumulation of malondialdehyde (MDH), indicating that lipid peroxidation affected chlorophyll pigments. From the second week of acclimation, photosynthetic pigment content significantly increased and MDH content decreased. The net photosynthetic rate and leaf carotenoid content showed almost linear increases throughout the acclimation period. Activity of antioxidant enzymes, namely, superoxide dismutase, catalase, and peroxidases, consistently increased throughout the acclimation period, corresponding with the accumulation of photosynthetic pigments, thus demonstrating the role of the improved antioxidant enzymatic defense system during acclimation. A comparison of parent plant DNA with that of the greenhouse acclimated plants using random amplified polymorphic DNA and inter-simple sequence repeat markers showed a monomorphic pattern indicating genetic stability and the suitability of the method for micropropagation of L. speciosa.

20.
Anticancer Agents Med Chem ; 22(20): 3416-3437, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35125087

RESUMO

AIMS: The present study aimed to isolate and characterize chemical compounds from Anthocephalus cadamba Miq. bark and evaluate their anticancer activity by in silico, molecular docking, and in vitro studies. BACKGROUND: Anthocephalus cadamba is a traditionally used Indian medicinal plant. The anticancer and phytochemical properties of this plant remain unexplored except for a few studies. OBJECTIVES: The objective of the study was to evaluate the antiproliferative activity of extract and fractions against breast cancer and prostate cancer cell lines and isolate and characterize active compounds from bio-active guided fractions. Moreover, the anticancer activity of isolated compounds against breast and prostate cancer cell lines was also evaluated, in addition to in silico and molecular docking interactions of isolated compounds with VEGFR2 and PDGFRα target proteins. METHODS: The compounds were isolated and purified with the help of repeated column chromatography, and spectral techniques, such as 1D, 2D NMR, and GC-MS/MS, were used to identify and elucidate the structure of the compounds. Moreover, prediction of activity spectra for substances, physiochemical properties, bioactivity radar prediction, bioactivity score, natural-product likeness, ADME, and toxicity parameters of isolated compounds (AC-1 to AC-4) was performed through various in-silico databases and servers. To evaluate the docking interaction profile and binding energies of compounds, three docking tools were utilized, such as AutoDock, AutoDock Vina, and iGEMDOCK, against two targets VEGFR2 and PDGFRα. MD simulation was performed through ligand and receptor molecular dynamic server (LARMD). RESULTS: It was found that the A. cadamba bark chloroform fraction demonstrated a significant inhibitory effect against MDA-MB-231, MCF-7, and PC-3 cells in a dose-time-dependent manner. The bioassay-guided isolation afforded four molecules AC-1 to AC-4 from chloroform fraction. Moreover, the GC-MS/MS profiling identified fourteen new molecules which were not reported earlier from A. cadamba. The in-silico study showed that the isolated compounds (AC-1 to AC-4) followed Lipinski's rule and had good oral bioavailability. While compound AC-4 had positive bioactivity scores except for kinase inhibitor activity. The ADMET profiling revealed that AC-4 was non-toxic and easily absorbed in the human intestine, and transportable in the blood-brain barrier compared to AC-1, AC-2, AC-3, and standard drug doxorubicin. Molecular docking and MD simulation assessment also signified AC-4 anticancer activity with dual inhibitory action against the target proteins VEGFR2 and PDGFRα amongst the studied compounds. The in vitro cell viability assay of isolated compounds demonstrated that AC-1 showed IC50 (µg/mL) value of 34.96 ±3.91, 47.76±3.80 69.1±4.96, AC-2; 68.26±4.22, 54.03±5.14, >100, AC-3; 35.34±4.14, 51.5±51.5, 70.8±5.25 and AC-4; 44.2±3.57, 24.2±2.67, 51.2±2.54 for MDA-MB-231, MCF-7, and PC-3 cancer cell lines, respectively and compared with standard drug doxorubicin. Moreover, fluorescence microscopy confirmed the apoptogenic property of compounds. We also found that AC-4 exhibited significant intracellular ROS production in breast cancer cells, thereby inducing apoptosis and eventually cell death. CONCLUSION: In conclusion, A. cadamba afforded four pure molecules AC-1 to AC-4 with the identification of fourteen new compounds. The entire in-silico studies concluded that the AC-4 compound had better oral bioavailability, bioactivity score, and ADMET profile among studied molecules. Molecular docking analysis and MD simulation also supported AC-4 dual inhibitory action against both VEGFR2 and PDGFRα receptors. Moreover, the isolated molecules AC-1, AC-2, AC-3, and AC-4 were found to be active against MDA-MB-231, MCF-7, and PC-3 cancer cells. The molecule AC-4 was found to induce ROS-mediated apoptosis in breast cancer cells. It was found that the anticancer inhibitory potentiality of AC-4 is directed to its molecular stereochemistry which specifically binds to the target proteins of breast cancer cells with no toxicological effect. Therefore, AC-4 is suggested to be an effective aspirant for novel drug design and discovery.


Assuntos
Antineoplásicos , Neoplasias da Mama , Neoplasias da Próstata , Humanos , Masculino , Antineoplásicos/farmacologia , Antineoplásicos/química , Clorofórmio , Doxorrubicina , Ligantes , Simulação de Acoplamento Molecular , Casca de Planta/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Espécies Reativas de Oxigênio/análise , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/análise , Espectrometria de Massas em Tandem , Feminino
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