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Different stress condition stimulates the expression level of insulin-like growth factor receptor II (IGF-IIR) in cardiomyoblasts that lead to apoptosis. Tanshinone IIA (TSN), a pharmacologically active component from Danshen, has been shown cardioprotective effects against cardiac apoptosis induced by several stress conditions. Therefore, this study was conducted to assess the cardioprotective effects of TSN IIA mediated through the estrogen receptor (ER) in order to inhibit the Leu27IGF-II-enhanced IGF-IIR-mediated cardiac apoptosis. The estrogenic activity of TSN IIA was examined after myocardial cells were pretreated with the ER antagonist, and inhibited the phospho-inositide-3 kinase (PI3K). Here, we found that TSN IIA significantly induced ER that phosphorylated Akt. Further, Akt activation considerably suppressed the Leu27IGF-II induced IGF-IIR expression level and the downstream effectors, including Gαq and calcineurin as well as mitochondrial dependent apoptosis proteins including Bad, cytochrome c, and active caspase-3 that result in cardiac apoptosis resistance. However, the western blot analysis, JC-1 staining, and terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay revealed that TSN IIA attenuated Leu27IGF-II-induced IGF-IIR mediated cardiac apoptosis was reversed by an ER antagonist such as ICI 182780, and PI3K inhibition. All these findings demonstrate that TSN IIA exerts estrogenic activity, which can activate PI3K-Akt pathway, and thereby inhibits Leu27IGFII induced IGF-IIR mediated cardiac apoptosis. Thus, TSN IIA can be considered as an effective therapeutic strategy against IGF-IIR signaling cascade to suppress cardiac apoptosis.

Over the past few decades, many of the phytochemicals have been shown to possess extraordinary anticancer effects, clinical tested, approved as drugs, and currently in use. A considerable number of phytochemicals either as a single-agent or combined with existing anticancer drugs at pre-clinical and clinical levels have been evaluated to date. However, the clinical trials on phytochemical evaluations against the world's top-ranked cancer, NSCLC, was found to be a very little. Some of the phytochemicals that showed significant anticancer activity against NSCLC in vitro and/or in vivo at the preclinical levels are highlighted in this review article. There are several impediments such as poor solubility, poor bioavailability, low stability, a requirement of high doses, safety and toxicity that limits the wide-spread use of phytochemicals in clinical oncology. Nanotherapeutic systems can help to overcome the aforementioned issues and wide open the gates to focus on phyto-oncotherapy, in particular NSCLC. The current review aims to summarize the importance of phytochemicals as anticancer agents, with a special mention on nano-formulations to treat non-small cell lung cancer (NSCLC).

Pathological cardiac hypertrophy is associated with many diseases including hypertension. Recent studies have identified important roles for microRNAs (miRNAs) in many cardiac pathophysiological processes, including the regulation of cardiomyocyte hypertrophy. However, the role of miR-145-5p in the cardiac setting is still unclear. In this study, H9C2 cells were overexpressed with microRNA-145-5p, and then treated with Ang-II for 24 h, to study the effect of miR-145-5p on Ang-II-induced myocardial hypertrophy in vitro. Results showed that Ang-II treatment down-regulated miR-145-5p expression were revered after miR-145-5p overexpression. Based on results of bioinformatics algorithms, paxillin was predicted as a candidate target gene of miR-145-5p, luciferase activity assay revealed that the luciferase activity of cells was substantial downregulated the following co-transfection with wild paxillin 3'UTR and miR-145-5p compared to that in scramble control, while the inhibitory effect of miR-145-5p was abolished after transfection of mutant paxillin 3'UTR. Additionally, overexpression of miR-145-5p markedly inhibited activation of Rac-1/ JNK /c-jun/ NFATc3 and ANP expression and induced SIRT1 expression in Ang-II treated H9c2 cells. Jointly, our study suggested that miR-145-5p inhibited cardiac hypertrophy by targeting paxillin and through modulating Rac-1/ JNK /c-jun/ NFATc3/ ANP / Sirt1 signaling, therefore proving novel downstream molecular pathway of miR-145-5p in cardiac hypertrophy.

The moisture in the compressed air causes severe damages to the devices that uses compressed air. Cyclone separator is used to separate moisture from the compressed air. Computational fluid dynamics is used as a tool to analyse the cyclone separator where a flow of compressed air is passed through the inlet then the compressed air is made to strike the vane and thus the swirling movement is created. By this an internal flow is made up. Fluid flows, pressure of compressed air, velocity of compressed air are the parameters that are considered here. The above said parameters are kept constant and by changing the vane in different angles, the velocity, pressure, and path line in the separator are simulated. The pressure drop obtained from the analysis according to different angles of vane is compared and the vane angle that produces the highest-pressure drop is found by the help of computational fluid dynamics. The velocity of the compressed air flow is also checked whether it is below the erosion velocity limit so that the erosion of the parts inside the cyclone separator will be predicted. The vane angle that produces the maximum pressure drop and velocity lesser than the erosion velocity limit is the most efficient in removing the moisture from the compressed air.

In this study, we used ICI 182 780 (ICI), an estrogen receptor (ER) antagonist, to investigate the estrogenic activity of Danshen, and to further explored whether Danshen extract can block Leu27IGF-II-induced hypertrophy in H9c2 cardiomyoblast cells. We first used an IGF-II analog Leu27IGF-II, which specifically activates IGF2R signaling cascades and induces H9c2 cardiomyoblast cell hypertrophy. However, Danshen extract completely inhibited Leu27IGF-II-induced cell size increase, ANP and BNP hypertrophic marker expression, and IGF2R induction. We also observed that Danshen extract inhibited calcineurin protein expression and NFAT3 nuclear translocation, leading to suppression of Leu27IGF-II-induced cardiac hypertrophy. Moreover, the anti-Leu27IGF-II-IGF2R signaling effect of Danshen was totally reversed by ICI, which suggest the cardio protective effect of Danshen is mediated through estrogen receptors. Our study suggests that, Danshen exerts estrogenic activity, and thus, it could be used as a selective ER modulator in IGFIIR induced hypertrophy model.

Picrasidine I is a dimeric alkaloid derived from a Southern Asian plant Picrasma quassioides and demonstrated to possess pharmacological activities, such as anti-inflammatory and anti-osteoclastogenic effects. However, its potential anticancer effect remains unclear. In the present study, anticancer activity of picrasidine I was assessed by treating oral squamous cell carcinoma cells with different concentrations of picrasidine I (20, 30, and 40 μM) for 24, 48, and 72 h. The findings revealed that picrasidine I reduced the cell viability in a dose-dependent manner. Picrasidine I exerted its cytotoxic effect through arresting cell cycle at G2/M phase by downregulating cyclin A, cyclin B, CDK4, and CDK6, and inducing apoptosis in oral cancer cells. The induction of apoptosis was evidenced by increasing expression of death receptors, disruption of mitochondrial membrane potential, increased activation of PARP and caspases 3, 8, and 9, enhanced expression of proapoptotic mediators (Bak and Bim L/S), and reduced expression of antiapoptotic mediators (Bcl-2 and Bcl-xL). Moreover, analysis of MAPK signaling pathway revealed that picrasidine I-mediated proapoptotic activities by downregulating JNK phosphorylation. Taken together, the study identifies picrasidine I as a potent anticancer agent that can be used as a therapeutic intervention against oral squamous cell carcinoma.

Despite multidisciplinary therapy, the prognosis is poor for esophageal squamous cell carcinoma (ESCC). In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery could provide survival benefits to some patients. Here, we aimed to identify for tumor therapy response a biomarker based on RNA sequencing. We collected endoscopic biopsies of 32 ESCC patients, who were divided according to nCRT response, into two groups: the complete response group (n = 13) and the non-complete response group (n = 19). RNA-sequencing data showed that 464 genes were differentially expressed. Increased in non-complete response group, 4 genes increased expressions were AGR2 (anterior gradient 2), GADD45B (growth arrest and DNA damage inducible beta), PPP1R15A (protein phosphatase 1 regulatory subunit 15A) and LRG1 (leucine rich alpha-2-glycoprotein 1). The areas under the curve (AUC) of the AGR2 gene was 0.671 according to read counts of RNA-seq and therapy response of nCRT. In vitro study showed that apoptosis cell was significantly increased in the AGR2-knockdown TE-2 cell line treated with cisplatin and 5-Fluorouracil (5-FU), when compared with si-control. Results suggest that in ESCC, the AGR2 gene is a promising and predictive gene marker for the response to anti-tumor therapy.

Urothelial bladder cancer is rapidly spreading across Western countries, and therapy has shown little-to-moderate effects on bladder cancer. Thus, focusing on curbing cancer incidence has become crucial. The aim of the present study was to investigate the anticancer effects of Tannic acid (TA) in human bladder cancer. UMUC3 bladder cancer cells were treated with different concentrations of TA (0-100 µM) and tested for cell viability, colony formation, and apoptosis. The involvement of the phosphoinositide-3 kinase (PI3K)/Akt pathway in the action of TA was examined. TA treatment significantly inhibited the viability and increased percentage of apoptotic cells, thereby decreasing antiapoptotic proteins (BCL2, MCL-1, and BCL-XL) expression, resulting in the Caspase-3 activation. TA treatment decreased stem cell markers expression such as SOX2, OCT4, and NANOG. Additionally, TA treatment significantly reduced the phosphorylation levels of Akt in bladder cancer cells. Our study demonstrates the growth inhibitory effects of TA in bladder cancer cells, and highlights its potential as an anticancer agent for bladder cancer.

The maintenance of uniformity in food grade among the market available edible elements is quite debatable now-a-days. This ambiguity is mere consequence of versatility in the product vendors and various materials used for manufacturing the same. One of the important factors which governs the processed food's standard is its shelf life with and without refrigeration. It's a known fact that the food becomes a house for production of yeast, mold, bacteria and many other parasites on an extended shelf life. This process will route a way for aerobic and anaerobic culture in the food, for which the dominant end product would be methane (CH 4 ). The proposed work aims at providing an amicable and affordable IoT device which is capable of identifying the extent of food spoilage and decides the degree of edibility based upon methane dissipation. The designed product additionally also features the measurement of humidity and temperature to ensure annunciation of food decay.

Habitual chewing of the areca nut increases the risk of mortality owing to cardiovascular disease, but few reports have revealed the cardiotoxicity mechanism of the areca nut. Arecoline has been reported to be the primary toxic constituent in the areca nut. In order to study the acute cardiotoxicity of the areca nut in the development of pathologic heart hypertrophy, we induced heart injury in rats using arecoline. Arecoline at a low dosage (5 mg/kg/day) or a high dosage (50 mg/kg/day) was intraperitoneally injected to Sprague-Dawley rats for 21 days. The change of heart function and biochemical pathways were investigated with echocardiography and Western blot. The results were presented that heart functions were weakened by arecoline stimulation, and western blotting analysis revealed an elevation in BNP levels in the heart after arecoline exposure. Arecoline induced IL-6-mediated activation of the MEK5/ERK5 and JAK2/STAT3 pathways, as well as mitogen-activated protein kinase signaling cascades. Further, arecoline increased the calcineurin and NFATc3 levels in the heart. In summary, our results suggest that arecoline causes significantly cardiotoxicity and heart damage by inducing several hypertrophy-related signaling pathways, including IL-6-induced MEK5/ERK5, JAK2/STAT3, mitogen-activated protein kinases, and calcineurin signaling pathways. The study elucidated, for the first time, the possible cardiac hypertrophy mechanisms underlying the cardiotoxicity of the areca nut.

BackgroundEsophageal squamous cell carcinoma (ESCC) still has a poor prognosis despite the use of multidisciplinary therapy. In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery might provide survival benefits to some patients. MethodsIn this study, we aimed to identify biomarker to predict tumor response against neoadjuvant chemoradiotherapy (nCRT) by next-generation sequencing (NGS).ResultsOur data showed that 464 genes was differentially expressed ESCC specimens, in which AGR2 was 2.8 fold up-regulated in the patients with Non-complete response before nCRT than complete response group. In vitro study showed that, AGR2 was significantly reduced in AGR2 knockdown CE146T/VGH, TE2, and CE48T/VGH cells. MTT assay indicated that cell viability of AGR2-knockdown TE-2 cell line significantly decreased following 2.5µM cisplatin and 3µM 5-FU treatment. Furthermore, 6µM cisplatin and 20 µM 5-FU treatment greatly decreased AGR2-knockdown-CE48T/VGH, CE146T/VGH and TE-2 cells compared to control group. We also found in AGR2-knockdown cells, that protein level of p21 was increased in comparison with the control group. ConclusionsThis study suggest that AGR-2 as a promising and potential prediction gene marker dataset for response to neoadjuvant chemoradiation in ESCC.

Advanced-stage oral cancers with lymph node metastasis are associated with poor prognosis and a high mortality rate. Although recent advancement in cancer treatment has effectively improved the oral cancer prognosis, the majority of therapeutic interventions are highly expensive and are associated with severe sideeffects. In the present study, we studied the efficacy of a diarylheptanoid derivative, platyphyllenone, in modulating the metastatic potential of human oral cancer cells. Specifically, we treated the human oral cancer cells (FaDu, Ca9-22, and HSC3) with different concentrations of platyphyllenone and measured the cell proliferation, migration, and invasion. The study findings revealed that platyphyllenonesignificantly inhibited the motility, migration, and invasion of human oral cancer cells. Mechanistically, platyphyllenone reduced p38 phosphorylation, decreased β-catenin and Slug, increased E-cadherin expression, and reduced cathepsin L expression, which collectively led to a reduction in cancer cell migration and invasion. Taken together, our study indicates that platyphyllenone exerts significant anti-metastatic effects on oral cancer cells by modulating cathepsin L expression, the MAPK signaling pathway, and the epithelial–mesenchymal transition process.

The industrial heating furnace (IHF) is a system that requires continuous monitoring and control over the temperature. A small deviation in the temperature may create a huge impact on the system. So, there is a need for proper control for IHF. The conventional way is using PID (Proportion + Integral + Derivative) controller as the process controller in industries. Many standard tuning algorithms are present to compute gain values for the PID controller. The drawback of these conventional controllers is poor disturbance rejection as these are tuned offline to the system so that they cannot address the disturbances that occur while the system is working. So, there is a need for an artificial intelligent controller that can rectify the disturbance that occurs while the system is running. This can be achieved by using Fuzzy logic based controller that feeds the gain values externally to the PID controller according to the disturbance. The entire system design is simulated with the help of MATLAB/Simulink software. The outcome depicts that the proposed fuzzy-based controller has the best dynamic performance, rapidity, and good robustness.

Heat exchangers are commonly used in industries for the transfer of heat from one fluid to another fluid or from one form to another form. In this process of heat transfer, there is a need for continuous monitoring and control of the system to achieve desired heat levels. Normally, a robust PID controller is used for this purpose. To tune these PID controllers, many conventional methods are available. Of these methods, the OLTR (Open Loop Transient Response) methods are frequently used to obtain the gain parameters of the controllers. However, these methods are limited with respect to adjustment of steady-state error. As the heat exchanger systems are so sensitive to transients, any minor error can deviate the system behavior. In such systems, EPI (Error performance Index) methods provide a better system response by effectively nullifying the steady-state errors. Hence, this paper presents the design of PID controller gain parameters using various EPI methods. MATLAB/Simulink software is used to model the entire heat exchanger system and various control methods. The results justify that a better response is achieved with the use of ITAE based EPI method.

Epimedium, is used traditionally in Chinese medicine to treat infertility problems. In this study, we establish the cell model to elucidate the protective effect of epimedium against ES by analyzing the molecular relationship between mitochondrial dynamics and steroidogenesis and to explore the molecular mechanism focusing on mitochondria function relating to fertility. ES induced ROS accumulation in mitochondria and the epimedium treatment significantly reduced the ROS accumulation. Furthermore, mitochondria morphology was restored to elongated shape following epimedium treatment. Epimedium treatment promoted dynamin-associated protein 1 (Drp1)-mediated steroidogenesis pathway by upregulating PKA, CREB, Drp1, and StAR protein expression in response to ES exposure in Leydig cells. Moreover, it was also identified that, CREB plays an important role in epimedium activation in Drp1-mediated steroidogenesis signaling pathway by increasing, phospho-CREB expression in nucleus. Testosterone level is decreased in ES-exposed cells; however, the testosterone level was increased after epimedium treatment. In conclusion, epimedium treatment improved mitochondria function in ES-exposed Leydig cells and activated downstream Drp1-dependent steroidogenesis by CREB mediated signaling pathway.

Polyoxyethylene tallow amine (POEA) is a nonionic surfactant added to insecticide and herbicide formulations. Experimental data have been shown the toxic effects of POEA on aquatic organisms and remain to be a serious concern. In this study, total of thirty-two potential bacteria that were isolated from herbicide-contaminated soil samples showed the ability to use POEA as the sole carbon and energy source. In which, a bacterial strain LA was further investigated based on the efficiency utilization of POEA and classified as Kosakonia oryzae by the 16S rRNA gene. Response surface methodology was successfully applied to understand the interaction of distinct factors on POEA degradation by LA strain. Degradation of POEA was confirmed with UV–Visible spectrophotometric analysis and HPLC analysis. The POEA utilization mechanism was explored by target gene detection and carbon source utilization. The results indicate that strain LA has the potential to serve as an in situ candidate for bioremediation polluted by POEA.

The aim of this study was to investigate the effects of longan flower (LF) water extract on cardiac apoptotic and survival pathways in rat models of fructose-induced metabolic syndrome. The study findings revealed that the levels of glucose, insulin, triglyceride, and cholesterol and TUNEL-positive apoptotic cells were significantly increased in the HF group compared with the control group; whereas, the levels were decreased in the HFLF group. The expressions of Fas, FADD, and activated caspases 8 and 3, as well as the expressions of Bax, Bak, Bax/Bcl-2, Bak/Bcl-xL, cytosolic cytochrome c, and activated caspases 9 and 3 were increased in the HF group were significantly reversed in HFLF administrated group. Furthermore, LF extract increased IGF-1R, p-PI3K, p-Akt, Bcl-2, and Bcl-xL expression compared to HF group. Taken together, the present findings help identify LF as a potential cardioprotective agent that can be effectively used in treating fructose-induced metabolic syndrome.

Maintaining a consistent liquid level is required for many day-to-day applications such as washing machines, water dispensers, etc. In order to effectively cater the requirements of all these traditional applications as well as modern applications such as automated-coffee machines, the liquid level should be controlled smoothly and rapidly. In the overall operation of a system, controller plays most important role to protect the system from disturbances and to maintain the stability. There are two types of controllers, namely offline/classical and online controller. Most renowned and simple classical controller that is widely used for many applications is proportional plus integral plus derivative (PID) controller, whose effectiveness relies on proper design of PID gains. Further, due to varying operating conditions, it is always required to design suitable PID gains to obtain the desired response from the system. There are many state-of-the-art methods available for tuning PID gains. However, picking a right method with respect to the given system is always a tough task. Besides, the classical methods cannot adjust the PID gains according to the disturbance. These problems are addressed in this chapter by proposing fuzzy logic-based PI tuning method. A detailed quantitative assessment of proposed method with various state-of-the-art methods such as classical tuning methods and artificial neural network method was presented. Various time domain performance indices are computed to estimate the efficacy of the proposed method. Using these indices, this paper concludes the proposed fuzzy logic theory-based PI controller tuning method provide better system response over traditional methods.

Physical exercise (PE) improves physical performance, mental status, general health, and well-being. It does so by affecting many mechanisms at the cellular and molecular level. PE is beneficial for people suffering from neuro-degenerative diseases because it improves the production of neurotrophic factors, neurotransmitters, and hormones. PE promotes neuronal survival and neuroplasticity and also optimizes neuroendocrine and physiological responses to psychosocial and physical stress. PE sensitizes the parasympathetic nervous system (PNS), Autonomic Nervous System (ANS) and central nervous system(CNS) by promoting many processes such as synaptic plasticity, neurogenesis, angiogenesis, and autophagy. Overall, it carries out many protective and preventive activities such as improvements in memory, cognition, sleep and mood; growth of new blood vessels in nervous system; and the reduction of stress, anxiety, neuro-inflammation, and insulin resistance. In the present work, the protective effects of PE were overviewed. Suitable examples from the current research work in this context are also given in the article.

Power electronics based cuk converter finds many practical and industrial applications such as renewable energy systems, hybrid electric vehicle, electronic voltage regulators, etc., to provide required voltage regulation between input DC stage and output DC stage. For the effective operation of all these kinds of practical applications, it seeks a quick and smooth response from a cuk converter along with the regulated DC output magnitude. The converter control is achieved through a closed-loop PID (proportional cum integral cum derivative) controller. Hence, the efficacy of the overall converter depends on how well the PID gain specifications are designed. There are many methods available for the tuning of PID controller gain specifications, but, the identification of better methods is a tedious task. Further, a method identified as best for a given system can’t be generalized as it may not suit for other systems. Hence, a better method for PID tuning has to be identified with respect to each and every system. Keeping this in mind, this paper provides a comprehensive investigation of all the key tuning methods and suggests the best one for cuk converter control with the help of time-domain performance index and frequency-domain stability index. The analysis is done using MATLAB/Simulink software models.

Epidemiological studies and experimental data have shown that the incidences of hepatocellular carcinoma in men are more frequent than in women. Evidence suggests that imbalance of hormones, including estrogen, androgen, prolactin, and growth hormone, modifies liver tumorigenesis. In this present study, we investigated how estrogen and estrogen receptor 2 (ESR2), regulates the cell cycle mechanism in Hep3B hepatocellular carcinoma cell line. Our results showed that ESR2 overexpression in the presence of 10⁻⁸ M 17-β-estradiol downregulated c-myc and cyclin D1 expression and simultaneously upregulated p27 expression. However, flow cytometry and MTT assays showed only minor G₁ phase arrest without affecting cell viability. Taken together, these observations indicate that ESR2 is required to lower tumorigenesis in males by altering cell cycle proteins in a ligand-dependent manner.