Muhammad Mansoor Khan

Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways

Gastric cancer is the fourth most commonly diagnosed cancer with the second highest mortality rate worldwide. Surgery, chemotherapy and radiation therapy are generally used for the treatment of stomach cancer but only limited clinical response is shown by these therapies and still no effectual therapy for advanced gastric adenocarcinoma patients is available. Therefore, there is a need to identify other therapeutic agents against this life-threatening disease. Plants are considered as one of the most important sources for the development of anticancer drugs. Magnolol, a natural compound possesses anticancer properties. However, effects of Magnolol on human gastric cancer remain unexplored. The effects of Magnolol on the viability of SGC-7901 cells were determined by the MTT assay. Apoptosis, mitochondrial membrane potential and cell cycle were evaluated by flow cytometry. Protein expression of Bcl-2, Bax, caspase-3 and PI3K/Akt was analysed by Western blotting. Magnolol induced morphological changes in SGC-7901 cells and its cytotoxic effects were linked with DNA damage, apoptosis and S-phase arrest in a dose-dependent manner. Magnolol triggered the mitochondrial-mediated apoptosis pathway as shown by an increased ratio of Bax/Bcl-2, dissipation of mitochondrial membrane potential (ΔΨm), and sequential activation of caspase-3 and inhibition of PI3K/Akt. Additionally, Magnolol induced autophagy in SGC-7901 cells at high concentration but was not involved in cell death. Magnolol-induced apoptosis of SGC-7901 cells involves mitochondria and PI3K/Akt-dependent pathways. These findings provide evidence that Magnolol is a promising natural compound for the treatment of gastric cancer and may represent a candidate for in vivo studies of monotherapies or combination antitumor therapies.

A novel synchronization scheme for grid-connected converters by using adaptive linear optimal filter based PLL (ALOF–PLL)

Abstract This paper proposes a novel grid synchronization scheme using a new phase-locked loop (PLL) scheme based on the adaptive linear optimal filtering (ALOF) technique. The problem formulation of the proposed ALOF is based on decomposing grid voltage signal into inner product of two vectors, namely, the vector of trigonometric functions and the vector of coefficients, corresponding to the input vector and the weight vector of the closed-loop adaptation algorithm by using least-mean-square (LMS) optimization algorithm. The coefficient of the fundamental component of the grid voltage is used as input signal for the PLL and the phase angles of the trigonometric functions are obtained from the output of the PLL recursively. The mathematical derivation of the weights updating law and the stability analysis of the ALOF–PLL are presented. Besides, the parameter selection for optimal performance is also discussed in terms of continuous domain (s-domain) analysis, discrete domain (z-domain) analysis and time domain simulations. The proposed ALOF–PLL shows the characteristic of band-pass filter at fundamental frequency and a notch filter at the harmonic frequencies. Finally, a detailed comparison with the existing single-phase and three-phase grid synchronization methods is also presented, and the proposed ALOF–PLL is found to have overwhelming advantages over the existing grid synchronization methods in terms of tracking accuracy, dynamic response and immunity to grid voltage disturbances, such as voltage sag/swell, phase-angle jump, harmonics, unbalance, random noises and frequency jump, etc. The validity and effectiveness of the ALOF–PLL is substantially confirmed by the extensive simulation results obtained from Matlab/Simulink.

Robust Deadbeat Control Scheme for a Hybrid APF With Resetting Filter and ADALINE-Based Harmonic Estimation Algorithm

A novel hybrid active power filter (HAPF) topology is proposed, which shows advantages of the conventional HAPF and the LCL filter in terms of reduced dc-link voltage, lower switching ripples, and less electromagnetic interference injection. To enhance the noise rejection capability of the digital controller, the resetting filters (RFs) are utilized as prefilters before the analog/digital sampling stage. A robust deadbeat current control law is derived based on the average current tracking scheme, where the effect of the RFs is favorably incorporated. To alleviate the difficulties in current controller design, the ac-side capacitor voltage of the HAPF is estimated by using the adaptive linear neural network identifier in the load current feedforward loop. Hence, a simple proportional controller is utilized in the inner current loop. Moreover, the grid current feedback and load current feedforward strategies are used to achieve precise current tracking and fast dynamic response. A 75-kVA prototype system is built for verification. The validity of the proposed HAPF and its control algorithms are confirmed by the experimental results.

Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction

Signal transducer and activator of transcription 3 (STAT3) constitutively expresses in human liver cancer cells and has been implicated in apoptosis resistance and tumorigenesis. Alantolactone, a sesquiterpene lactone, has been shown to possess anticancer activities in various cancer cell lines. In our previous report, we showed that alantolactone induced apoptosis in U87 glioblastoma cells via GSH depletion and ROS generation. However, the molecular mechanism of GSH depletion remained unexplored. The present study was conducted to envisage the molecular mechanism of alantolactone-induced apoptosis in HepG2 cells by focusing on the molecular mechanism of GSH depletion and its effect on STAT3 activation. We found that alantolactone induced apoptosis in HepG2 cells in a dose-dependent manner. This alantolactone-induced apoptosis was found to be associated with GSH depletion, inhibition of STAT3 activation, ROS generation, mitochondrial transmembrane potential dissipation, and increased Bax/Bcl-2 ratio and caspase-3 activation. This alantolactone-induced apoptosis and GSH depletion were effectively inhibited or abrogated by a thiol antioxidant, N-acetyl-L-cysteine (NAC). The data demonstrate clearly that intracellular GSH plays a central role in alantolactone-induced apoptosis in HepG2 cells. Thus, alantolactone may become a lead chemotherapeutic candidate for the treatment of liver cancer.

Jaceosidin Induces Apoptosis in U87 Glioblastoma Cells through G2/M Phase Arrest

Artemisia argyi is a widely used medicinal plant in China. The present study was designed to identify the bioactive constituents with antiglioma activity from leaves of Artemesia argyi. A bioactivity guided approach based on MTT assay for cells growth inhibition led to the isolation of a flavonoid, “jaceosidin” from ethanol extract of leaves of Artemesia argyi. The growth inhibitory effect of jaceosidin was explored using flow cytometry and Western blot studies. Our results showed that jaceosidin exerts growth inhibitory effect by arresting the cells at G2/M phase and induction of apoptosis. Furthermore, our study revealed that induction of apoptosis was associated with cell cycle arrest at G2/M phase, upregulation of p53 and Bax, decrease in mitochondrial membrane potential, release of cytochrome c, and activation of caspase 3. This mitochondrial-caspase-3-dependent apoptosis pathway was confirmed by pretreatment with caspase 3 inhibitor, Ac-DEVD-CHO. Our findings suggested that jaceosidin induces mitochondrial-caspase-3-dependent apoptosis in U87 cells by arresting the cell cycle at G2/M phase.

A novel harmonic-free power factor corrector based on T-type APF with adaptive linear neural network (ADALINE) control

Abstract A novel harmonic-free power factor correction (PFC) topology based on T-type active power filter (APF) is proposed in this paper. The proposed system has better stability characteristics compared to conventional shunt APF topologies and it is a natural filter for the non-linear load harmonic disturbances. The tuned passive filters are connected at the ac-side of the rectifier load, which are designed to provide fundamental reactive power compensation and eliminate majority of load harmonics in order to minimize the power rating and heat dissipation of the voltage source inverter (VSI). The control scheme is based on a decoupled state-space equations of the T-type APF using separate proportional-integral controllers in d-axis and q-axis of rotating reference frame synchronized with grid voltages, respectively. The fundamental components of load-side currents are feed-forwarded in the current control loop using two groups of synchronous frame adaptive linear neural networks (ADALINEs) to ensure a fast dynamic response. A proportional-integral controller is adopted in the outer voltage loop for balancing the active power flow of the dc-side capacitor of the VSI. The proposed power factor corrector topology is studied analytically and by simulation under various scenarios using Matlab/Simulink. The validity and effectiveness of the proposed topology as well as its control schemes are substantially confirmed by the simulation results.

Eupatilin: A flavonoid compound isolated from the artemisia plant, induces apoptosis and G2/M phase cell cycle arrest in human melanoma A375 cells

Eupatilin is a flavonoid compound isolated from the Artemisia plant. Eupitillin possesses antioxidant as well as potent anticancer properties. In this study, for the first time, we examined the anti-proliferative effects of Eupatilin in human melanoma A375 cells and its ability to induce apoptosis and cell cycle arrest. Eupatilin specifically induced morphological changes in A375 cells and was less toxic to the normal mouse splenocytes. The inhibitory effects of A375 cells were associated with the DNA damage, apoptosis, and cell cycle arrest at G2/M phase in a dose-dependent manner. The apoptotic effects of Eupatilin were further verified by using Annexin V-FITC/propidium iodide staining in flow cytometry. These results suggest that Eupatilin is an effective natural compound that worth further mechanistic and therapeutic studies against human melanoma.

A generalized framework for sampled-data model analysis of closed-loop PWM DC-DC converter system

In spite of the fact that, sampled-data models of PWM DC power converter systems (PDCS) are more accurate and natural, little effort has been made to use sampled-data techniques for stability analysis and synthesis of closed-loop PDCS. Instead, averaged models are typically used for control loop design, while detailed simulations are used for validating closed-loop performances. Recent developments in sampled-data control have resulted in new powerful tools for analysis and synthesis of periodic-system. Time lifting of continuous time signals/systems is one of such tools. In this paper, the authors introduce a generalized framework for sampled-data analysis of DC-DC power converter system based on continuous time lifting of signal/system. This framework will provide an adequate ground to tackle the hybrid nature of these systems. It has been shown that the general discrete-time model of a PDCS is equivalent to a time-lifted model for this class of systems and closed loop PDCS local stability problem can be described by an equivalent time-lifted system, which is finite rank linear discrete-time problem. Hence well-established analysis techniques in sampled-data control can instantly be applied for analysis of these systems. A system composed of two parallel buck-converters has been analyzed to demonstrate the proposed framework.

Increased differentiation capacity of bone marrow-derived mesenchymal stem cells in aquaporin-5 deficiency.

Mesenchymal stem cells (MSCs) are adult stem cells with a self-renewal and multipotent capability and express extensively in multitudinous tissues. We found that water channel aquaporin-5 (AQP5) is expressed in bone marrow-derived MSCs (BMMSCs) in the plasma membrane pattern. BMMSCs from AQP5(-/-) mice showed significantly lower plasma membrane water permeability than those from AQP5(+/+) mice. In characterizing the cultured BMMSCs from AQP5(-/-) and AQP5(+/+) mice, we found no obvious differences in morphology and proliferation between the 2 genotypes. However, the multiple differentiation capacity was significantly higher in AQP5(-/-) than AQP5(+/+) BMMSCs as revealed by representative staining by Oil Red O (adipogenesis); Alizarin Red S and alkaline phosphatase (ALP; osteogenesis); and type II collagen and Safranin O (chondrogenesis) after directional induction. Relative mRNA expression levels of 3 lineage differentiation markers, including PPARγ2, C/EBPα, adipsin, collagen 1a, osteopontin, ALP, collagen 11a, collagen 2a, and aggrecan, were significantly higher in AQP5(-/-) -differentiating BMMSCs, supporting an increased differentiation capacity of AQP5(-/-) BMMSCs. Furthermore, a bone-healing process was accelerated in AQP5(-/-) mice in a drill-hole injury model. Mechanistic studies indicated a significantly lower apoptosis rate in AQP5(-/-) than AQP5(+/+) BMMSCs. Apoptosis inhibitor Z-VAD-FMK increased the differentiation capacity to a greater extent in AQP5(+/+) than AQP5(-/-) BMMSCs. We conclude that AQP5-mediated high plasma membrane water permeability enhances the apoptosis rate of differentiating BMMSCs, thus decreasing their differentiation capacity. These data implicate AQP5 as a novel determinant of differentiation of BMMSCs and therefore a new molecular target for regulating differentiation of BMMSCs during tissue repair and regeneration.

Costunolide, a sesquiterpene lactone induces G2/M phase arrest and mitochondria-mediated apoptosis in human gastric adenocarcinoma SGC-7901 cells

Costunolide, a sesquiterpene lactone isolated from the Saussurea lappa possesses potent anticancer properties. In this study, for the first time we investigated the effects of costunolide on the cell viability, cell cycle and apoptosis in gastric adenocarcinoma SGC-7901 cells. The results showed that costunolide induced morphological changes and decreased the cell viability of SGC-7901 cells. Meanwhile, the parallel treatment of the costunolide to a normal splenocytes showed less strong effects. Deoxyribonucleic aci d (DNA) flow cytometric analysis demonstrated that costunolide markedly induced apoptosis of SGC-7901 cells and arrested cell cycle at G2/M phase in a time-dependent manner. Costunolide-induced apoptosis was regulated by activation of caspase-3 and down-regulation of Bcl-2. Furthermore, costunolide significantly induced the loss of mitochondrial membrane potential. It indicated that costunolide-induced apoptosis involved the mitochondria-dependent pathway in SGC-7901 cells. These in vitro results suggested that Costunolide should be further examined for in vivo activity and molecular mechanism in human gastric cancer. Key words: