Probable Molecular Mechanisms Research Articles

Study on impact of ethanol extracts from Sedum sarmentosum in inhibiting STAT-3 signaling and inducing apoptosis of human hepatocellular carcinoma cell line HepG2

To investigate the impact of ethanol extracts from Sedum sarmentosum (ESB) on STAT-3 signaling and its probable molecular mechanism in inducing apoptosis. MTT assay was used to detect the impact of ESB on HepG2 cell proliferation. FITC-Annexin V-FITC /PI double-labeling were used to investigate the impact on hepatoma carcinoma cell apoptosis. Western blot analysis was used to test the expression levels of cell apoptosis-related proteins Caspase-3, Caspase-9, PARP, P-STAT-3 (Tyr705) , STAT-3, Bcl-2, Mcl-1. ESB could notably inhibit proliferation of HepG2 cells, and induce HepG2 cell apoptosis, with the dose-dependent inhibitory effect. In addition, ESB could inhibit STAT-3 signaling, down-regulate Mcl-1 and Bcl-2 expressions, and induce degradation/activation of apoptosis-related proteins Caspase-3 and Caspase-9 and PARP degradation in a dose-dependent manner. ESB inhibits HepG2 cell proliferation and induces apoptosis by inhibiting STAT-3 signaling and Mcl-1 and Bcl-2 expressions.

Ginkgo biloba extract inhibits oxidized low-density lipoprotein (oxLDL)-induced matrix metalloproteinase activation by the modulation of the lectin-like oxLDL receptor 1-regulated signaling pathway in human umbilical vein endothelial cells

The overexpression of matrix metalloproteinases (MMPs) induced by oxidized low-density lipoprotein (oxLDL) has been found in atherosclerotic lesions. Previous reports have identified that oxLDL, via the upregulation of lectin-like ox-LDL receptor 1 (LOX-1), modulates the expression of MMPs in endothelial cells. Ginkgo biloba extract (GbE), from Ginkgo biloba leaves, has often been considered as a therapeutic compound for cardiovascular and neurologic diseases. However, further investigation is needed to ascertain the probable molecular mechanisms underlying the antiatherogenic effects of GbE. The aim of this study was to investigate the effects of GbE on oxLDL-activated MMPs of human endothelial cells and to test the involvement of LOX-1 and protein kinase C (PKC)-α, extracellular signal-regulated kinase (ERK), and peroxisome proliferator-activated receptor-γ (PPAR-γ). Human umbilical vein endothelial cells were stimulated with oxLDL, with or without GbE treatment. LOX-1 signaling and MMPs expression were tested by Western blotting or activity assay. Further, protein expression levels of PKC-α, ERK, nuclear factor-κB, and PPAR-γ were investigated by Western blotting. GbE inhibited the oxLDL-caused upregulation of MMP-1, MMP-2, and MMP-3. Pretreating with GbE reduced oxLDL-activated LOX-1 expression. Furthermore, pharmacologic inhibitors of free radicals, Ca(++), PKC, and GbE, inhibited the oxLDL-induced ERK and nuclear factor-κB activation. Lastly, GbE ameliorated the oxLDL-inhibited PPAR-γ function. Data obtained in this study indicate that GbE actives its protective effects by regulating the LOX-1-mediated PKC-α/ERK/PPAR-γ/MMP pathway, resulting in the suppression of reactive oxygen species formation and, ultimately, the reduction of MMPs expression in endothelial cells treated with oxLDL.

Apolipoprotein E4 impairs in vivo hippocampal long-term synaptic plasticity by reducing the phosphorylation of CaMKIIα and CREB.

Inheritance of the apolipoprotein E genotype ε4 (APOE4) is a powerful risk factor for most cases of late-onset Alzheimer's disease (AD). However, the effects of ApoE4 on the long-term synaptic plasticity and its underlying mechanism have not clearly investigated. In the present study, we examined the effects of ApoE4 on the hippocampal late-phase long-term potentiation (L-LTP) and investigated its probable molecular mechanisms by using in vivo field potential recording, immunohistochemistry, and western blotting. The results showed that: (1) intra-hippocampal injection of 0.2 μg ApoE4, but not ApoE2, before high frequency stimulations (HFSs) attenuated the induction of hippocampal L-LTP in the CA1 region, while injection of the same concentration of ApoE4 after HFSs, even at a higher concentration (2 μg), did not affect the long term synaptic plasticity; (2) ApoE4 injection did not affect the paired pulse facilitation in the hippocampal CA1 region; (3) ApoE4 injection before, not after, HFSs significantly decreased the levels of phosphorylated Ca2+/calmodulin-dependent protein kinase IIα (p-CaMKIIα) and phosphorylated cAMP response element-binding protein (p-CREB) in the hippocampus. These results demonstrated for the first time that ApoE4 could impair hippocampal L-LTP by reducing p-CaMKIIα and p-CREB, suggesting that the ApoE4-induced suppression of hippocampal long-term synaptic plasticity may contribute to the cognitive impairments in genetic AD; and both CaMKIIα and CREB are important intracellular targets of the neurotoxic ApoE4.

Association of purine asymmetry, strand-biased gene distribution and PolC within Firmicutes and beyond: a new appraisal.

BackgroundThe Firmicutes often possess three conspicuous genome features: marked Purine Asymmetry (PAS) across two strands of replication, Strand-biased Gene Distribution (SGD) and presence of two isoforms of DNA polymerase III alpha subunit, PolC and DnaE. Despite considerable research efforts, it is not clear whether the co-existence of PAS, PolC and/or SGD is an essential and exclusive characteristic of the Firmicutes. The nature of correlations, if any, between these three features within and beyond the lineages of Firmicutes has also remained elusive. The present study has been designed to address these issues.ResultsA large-scale analysis of diverse bacterial genomes indicates that PAS, PolC and SGD are neither essential nor exclusive features of the Firmicutes. PolC prevails in four bacterial phyla: Firmicutes, Fusobacteria, Tenericutes and Thermotogae, while PAS occurs only in subsets of Firmicutes, Fusobacteria and Tenericutes. There are five major compositional trends in Firmicutes: (I) an explicit PAS or G + A-dominance along the entire leading strand (II) only G-dominance in the leading strand, (III) alternate stretches of purine-rich and pyrimidine-rich sequences, (IV) G + T dominance along the leading strand, and (V) no identifiable patterns in base usage. Presence of strong SGD has been observed not only in genomes having PAS, but also in genomes with G-dominance along their leading strands – an observation that defies the notion of co-occurrence of PAS and SGD in Firmicutes. The PolC-containing non-Firmicutes organisms often have alternate stretches of R-dominant and Y-dominant sequences along their genomes and most of them show relatively weak, but significant SGD. Firmicutes having G + A-dominance or G-dominance along LeS usually show distinct base usage patterns in three codon sites of genes. Probable molecular mechanisms that might have incurred such usage patterns have been proposed.ConclusionCo-occurrence of PAS, strong SGD and PolC should not be regarded as a genome signature of the Firmicutes. Presence of PAS in a species may warrant PolC and strong SGD, but PolC and/or SGD not necessarily implies PAS.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-430) contains supplementary material, which is available to authorized users.

Neuroprotective Effects of Tetramethylpyrazine against Dopaminergic Neuron Injury in a Rat Model of Parkinson's Disease Induced by MPTP

Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disease. Although several hypotheses have been proposed to explain the pathogenesis of PD, apoptotic cell death and oxidative stress are the most prevalent mechanisms. Tetramethylpyrazine (TMP) is a biological component that has been extracted from Ligusticum wallichii Franchat (ChuanXiong), which exhibits anti-apoptotic and antioxidant roles. In the current study, we aimed to investigate the possible protective effect of TMP against dopaminergic neuron injury in a rat model of Parkinson's disease induced by MPTP and to elucidate probable molecular mechanisms. The results showed that TMP could notably prevent MPTP-induced dopaminergic neurons damage, reflected by improvement of motor deficits, enhancement of TH expression and the content of dopamine and its metabolite, DOPAC. We observed MPTP-induced activation of mitochondrial apoptotic death pathway, evidenced by up-regulation of Bax, down-regulation of Bcl-2, release of cytochrome c and cleavage of caspase 3, which was significantly inhibited by TMP. Moreover, TMP could prevent MPTP-increased TBARS level and MPTP-decreased GSH level, indicating the antioxidant role of TMP in PD model. And the antioxidant role of TMP attributes to the prevention of MPTP-induced reduction of Nrf2 and GCLc expression. In conclusion, in MPTP-induced PD model, TMP prevents the down-regulation of Nrf2 and GCLc, maintaining redox balance and inhibiting apoptosis, leading to the attenuation of dopaminergic neuron damage. The effectiveness of TMP in treating PD potentially leads to interesting therapeutic perspectives.

Computer search for molecular mechanisms of ulcerogenic action of nonsteroidal antiinflammatory drugs

"Peptic ulcers" is the most frequent side effect of non-steroidal anti-inflammatory drugs (NSAIDs). Experimental data indicate that pathogenesis of peptic ulcers cannot be explained only by the inhibition of cyclooxygenases. The knowledge about other molecular mechanisms of action of drugs related with development of peptic ulcers could be useful for design of new safe NSAIDs. However, considerable time and material resources are needed for corresponding experimental research. For simplification of experimental search, we have developed an approach for in silico identification of probable molecular mechanisms of action of drugs related with its side effects. We have created the set of NSAIDs containing 85 substances with data about structures and side effects. The computer program PASS (Prediction of Activity Spectra for Substances) predicting more than 3000 molecular mechanisms of action based on structural formula of substances was used to estimate unknown molecular mechanisms of action for these set of NSAIDs. Statistically significant relationships between predicted molecular mechanisms of action and development of peptic ulcers have been established. We have discovered twenty-six molecular mechanisms of action (two known previously and twenty-four new) which probably related with development of peptic ulcers. By analyzing of Gene Ontology data, signal and metabolic pathways, publications in Medline, we formulated hypotheses about the role of ten molecular mechanisms of action in pathogenesis of peptic ulcer.

The neuroprotection of Rattin against amyloid β peptide in spatial memory and synaptic plasticity of rats

Rattin, a specific derivative of humanin in rats, shares the ability with HN to protect neurons against amyloid β (Aβ) peptide-induced cellular toxicity. However, it is still unclear whether Rattin can protect against Aβ-induced deficits in cognition and synaptic plasticity in rats. In the present study, we observed the effects of Rattin and Aβ31-35 on the spatial reference memory and in vivo hippocampal Long-term potentiation of rats by using Morris water maze test and hippocampal field potential recording. Furthermore, the probable molecular mechanism underlying the neuroprotective roles of Rattin was investigated. We showed that intra-hippocampal injection of Rattin effectively prevented the Aβ31-35-induced spatial memory deficits and hippocampal LTP suppression in rats; the Aβ31-35-induced activation of Caspase-3 and inhibition of STAT3 in the hippocampus were also prevented by Rattin treatment. These findings indicate that Rattin treatment can protect spatial memory and synaptic plasticity of rats against Aβ31-35-induced impairments, and the underlying protective mechanism of Rattin may be involved in STAT3 and Caspases-3 pathways. Therefore, application of Rattin or activation of its signaling pathways in the brain might be beneficial to the prevention of Aβ-related cognitive deficits.

Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression

Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175–200g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF.

AMPK Activators Suppress Cervical Cancer Cell Growth through Inhibition of DVL3 Mediated Wnt/β-Catenin Signaling Activity

Recent evidence has suggested that AMPK activators may be applied as therapeutic drugs in suppressing cancer cell growth. However, the molecular mechanism of their suppressive function in cancer cells is still unclear. Here we show that AMPK activators impair cervical cancer cell growth through the reduction of DVL3, a positive regulator in Wnt/β-catenin signaling and an oncogenic player in cervical cancer tumorigenesis. By western blot and immunohistochemical analyses, we demonstrated that DVL3 was frequently upregulated and significantly associated with elevated β-catenin (P = 0.009) and CyclinD1 (P = 0.009) expressions in cervical cancer. Enforced expression of DVL3 elevated β-catenin and augmented cervical cancer cell growth, verifying that DVL3-mediated Wnt/β-catenin activation is involved in cervical cancer oncogenesis. On the other aspect, we noted that the cervical cancer cell growth was remarkably suppressed by AMPK activators and such cell growth inhibition was in concomitant with the reduction of DVL3 protein level in dose- and time-dependent manners. Besides, impaired mTOR signaling activity also reduced DVL3 expression. In contrast, co-treatment with Compound C (AMPK inhibitor) could significantly abrogate metformin induced DVL3 reduction. In addition, co-treatment with AM114 or MG132 (proteosomal inhibitors) could partially restore DVL3 expression under the treatment of metformin. Further in vivo ubiquitination assay revealed that metformin could reduce DVL3 by ubiquitin/proteasomal degradation. To our knowledge, this is the first report showing the probable molecular mechanisms of that the AMPK activators suppress cervical cancer cell growth by impairing DVL3 protein synthesis via AMPK/mTOR signaling and/or partially promoting the proteasomal degradation of DVL3.

Analysis of the changes in the basal cell region of oral lichen planus: An ultrastructural study

Context:Oral lichen planus (OLP) affects 0.5-1% of the total world's population. The histological features of oral lichen planus were first described by Dubreuill in 1906. Despite the advent of various techniques, the etiology of lichen planus remains obscure, although many theories for the etiology have been proposed.Aims:By studying OLP electron microscopically, we shall be emphasizing on the cells and its interactions in specific/altered surroundings which would help us in hypothesizing the effects of its specific cell-to-cell interactions.Materials and Methods:A total of 20 cases of oral lichen planus were selected and categorized into erosive and nonerosive forms based upon clinical pattern and confirmed as lichen planus by histopathological analysis. Tissue specimens thus obtained were cut into two halves and fixed in appropriate fixatives, i.e., neutral buffered formalin for paraffin-embedded hematoxylin and eosin stained sections and 2.5% glutaraldehyde and 2% paraformaldehyde for electron microscopic purpose respectively.Results:Ultrastructural comparison among the two forms showed significant differences between them. The basal layer showed cytoplasmic processes, intercellular spaces, desmosomes, nuclei, and signs of degeneration. The erosive form showed elongated, narrow or irregular cytoplasmic projections whereas the nonerosive showed short and broad based projections.Conclusions:The present study confirms the ultrastructural findings of basal cells in OLP with previous authors findings. Besides this, the categorization of the ultrastructural differences between erosive and nonerosive has raised the question of difference in the probable cellular and molecular mechanism between erosive and nonerosive forms.

Transient Variations in the Serum Concentrations of Cell Adhesion Molecules Following Retroperitoneal Laparoscopic and Open Radical Nephrectomy for Localized Renal-Cell Carcinoma

To evaluate differences in the serum concentrations of cell adhesion molecules (CAMs) after retroperitoneal laparoscopic and conventional open radical nephrectomies for localized renal-cell carcinoma (RCC). A total of 62 patients with stage T(1)N(0)M(0) RCC were randomized to either a retroperitoneal laparoscopic radical nephrectomy group (n=31) or an open group (n=31). Serum levels of soluble cluster of differentiation 44 splice variant 6 (sCD44v6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble epithelial cadherin (sE-cadherin) were determined independently by enzyme linked immunosorbent assay (ELISA) preoperatively, and on postoperative days 1 and 5. In addition, follow-up results were compared. On postoperative day 1, sCD44v6, sICAM-1, and sVCAM-1 levels increased significantly compared with preoperative levels in both groups (P<0.05). sE-cadherin levels decreased compared with preoperative levels in both groups without statistically significant differences (P>0.05). sCD44v6 levels in the retro-laparoscopy group were significantly higher than in the open group (P<0.05), while sICAM-1, sVCAM-1, and sE-cadherin levels showed no statistically significant differences between both groups (P>0.05). On postoperative day 5, all parameters in both groups were similar to preoperative values (P>0.05). Follow-up ranged from 7 to 18 months postoperatively in all 62 patients, with a 100% cancer-specific survival rate in each group. Although postoperatively higher serum concentrations of CAMs in both groups and significantly elevated sCD44v6 in the retro-laparoscopy group may be facilitated, the differences in CAMs between both groups are small and transient. Together with the similar follow-up results, this further supports previous studies that failed to show a difference in the oncologic outcomes between open and laparoscopic radical nephrectomy and provides a probable molecular mechanism.

Neurotransmitters as Regulators of Tumor Angiogenesis and Immunity: The Role of Catecholamines

The growing tumor employs various strategies to establish its growth, progression and spread in the host. Angiogenesis or formation of new blood vessels from existing ones and escape from immune surveillance are the two critical steps that ensure proper establishment and growth of the newly formed tumor. Thus understanding the novel pathways associated with tumor angiogenesis and immunity may lead to the development of newer therapeutic strategies using the regulators of these pathways to improve patient outcomes. These two pivotal steps in the process of tumorigenesis are governed by plethora of endogenous factors. The neuroendocrine molecules, which include the catecholamine neurotransmitters, dopamine, norepinephrine and epinephrine are of growing interest considering their varied and diverse regulatory roles both in the process of tumor angiogenesis and tumor immunity. This review focuses on the emerging roles of catecholamines in modulating tumor angiogenesis and immunity, and also discusses the probable molecular mechanisms of their actions. Understanding of this new group of endogenous regulators of tumor growth may lead to the development of newer therapeutic approaches for the treatment of cancer.

Diet and gastric neurons

Diet and gastric neurons

Synthesis of highly aligned and ultralong coordination polymer nanowires and their calcination to porous manganese oxide nanostructures

We have demonstrated an extremely facile procedure for the preparation of 3D porous manganese oxide nanostructures by pyrolysis of Mn-based coordination polymer nanowires. The highly aligned and ultralong Mn-based polymer nanowires with high chemical purities were prepared using nitrilotriacetic acid (NA) as a chelating agent by a one-step hydrothermal approach. In the synthesis, NA was slowly dissolved in water and bonded with manganese ions by carboxyl groups to form one-dimensional polymer nanowires under the protection of isopropyl alcohol, and then form highly aligned nanowire bundles. Control experiments show that the morphologies of polymer nanowires greatly depend on the precursor salts and ratios between deionized water and isopropyl alcohol. Based on the elemental analysis results, the probable molecular formula and growth mechanism have been proposed. The catalytic reaction results demonstrated that the as-prepared 3D porous manganese oxide nanostructure was a good support for aerobic oxidation of benzyl alcohol. Moreover, the catalysts can be easily separated and recycled.

Dynamic proteome in enigmatic preeclampsia: An account of molecular mechanisms and biomarker discovery

The coevolution of genomics and proteomics has led to advancements in the field of diagnosis and molecular mechanisms of disease. Proteomics is now stepping into the field of obstetrics, where early diagnosis of pregnancy complication such as preeclampsia (PE) is imperative. PE is a multifactorial disease characterized by hypertension with proteinuria, which is a leading cause of maternal and neonatal morbidity and mortality occurring in 5-7% of pregnancies worldwide. This review discusses the probable molecular mechanisms that lead to PE and summarizes the proteomics research carried out in understanding the pathogenicity of PE, and for identifying the candidate biomarker for diagnosis of the disease.

Differential gene expression and a functional analysis of PCB-exposed children: Understanding disease and disorder development

The goal of the present study is to understand the probable molecular mechanism of toxicities and the associated pathways related to observed pathophysiology in high PCB-exposed populations. We have performed a microarray-based differential gene expression analysis of children (mean age 46.1months) of Central European descent from Slovak Republic in a well-defined study cohort. The subset of children having high blood PCB concentrations (>75 percentile) were compared against their low PCB counterparts (<25 percentile), with mean lipid-adjusted PCB values of 3.02±1.3 and 0.06±0.03ng/mg of serum lipid, for the two groups, respectively (18.1±4.4 and 0.3±0.1ng/ml of serum). The microarray was conducted with the total RNA from the peripheral blood mononuclear cells of the children using an Affymetrix platform (GeneChip Human genome U133 Plus 2.0 Array) and was analyzed by Gene Spring (GX 10.0). A highly significant set of 162 differentially expressed genes between high and low PCB groups (p value <0.00001) were identified and subsequently analyzed using the Ingenuity Pathway Analysis tool. The results indicate that Cell-To-Cell Signaling and Interaction, Cellular Movement, Cell Signaling, Molecular Transport, and Vitamin and Mineral Metabolism were the major molecular and cellular functions associated with the differentially altered gene set in high PCB-exposed children. The differential gene expressions appeared to play a pivotal role in the development of probable diseases and disorders, including cardiovascular disease and cancer, in the PCB-exposed population. The analyses also pointed out possible organ-specific effects, e.g., cardiotoxicity, hepatotoxicity and nephrotoxicity, in high PCB-exposed subjects. A few notable genes, such as BCL2, PON1, and ITGB1, were significantly altered in our study, and the related pathway analysis explained their plausible involvement in the respective disease processes, as mentioned. Our results provided insight into understanding the associated molecular mechanisms of complex gene–environment interactions in a PCB-exposed population. Future endeavors of supervised genotyping of pathway-specific molecular epidemiological studies and population biomarker validations are already underway to reveal individual risk factors in these PCB-exposed populations.

All-trans retinoic acid (ATRA) downregulated MMP-9 by modulating its regulatory molecules

The vitamin A derivative all-trans retinoic acid (ATRA) is considered as a potent chemotherapeutic drug for its capability of regulating cell growth and differentiation. We aimed to study the effect of ATRA on MMP-9 in MDA-MB-231, human breast cancer cells and the probable molecular mechanisms through which ATRA exerts its effect. Results: Our experimental findings demonstrate that ATRA enters into the nucleus and regulates various signaling pathways viz. Integrin, FAK, ERK, PI-3K, NF-κB and also EGFR and down regulates pro-MMP-9 activity as well as its expression. As a result MDA-MB-231 cell migration on fibronectin medium gets retarded in presence of ATRA. ATRA up regulates TIMP-1 expression. Conclusions: Our study may help to understand the role of ATRA as a regulator of MMP-9 and the possible signaling pathways which are involved in this ATRA mediated down regulation of MMP-9.

Synthesis of Cobalt Ion‐Based Coordination Polymer Nanowires and Their Conversion into Porous Co3O4 Nanowires with Good Lithium Storage Properties

Cobalt ion-based coordination polymer nanowires were synthesized by using nitrilotriacetic acid (NA) as a chelating agent by a one-step hydrothermal approach. In the synthesis, cobalt ions were bonded with amino or carboxyl groups of NA to form one-dimension polymer nanowires, which can be confirmed by FTIR and TGA results. Our experimental results show that the morphologies of polymer nanowires greatly depend on the precursor salts, ratios between deionized water and isopropyl alcohol. The probable molecular formula and growth mechanism have been proposed. After heat treatment, the cobalt ion-based coordination polymer nanowires can be converted into porous Co(3)O(4) nanowires, which completely preserved the nanowire-like morphology. When used as anodes in lithium-ion batteries, the obtained porous Co(3)O(4) nanowires exhibited a high reversible capacity of 810 mA h g(-1) and stable cyclic retention at 30th cycle. The good electrochemical performance could be attributed to the porous nanostructure of Co(3)O(4), which provides pathways for easy accessibility of electrolytes and fast transportation of lithium ions.

Rational Design of In Situ Monolithic Imprinted Polymer Membranes for the Potentiometric Sensing of Diethyl Chlorophosphate – a Chemical Warfare Agent Simulant

AbstractMolecularly imprinted polymer membrane was prepared by semicovalent imprinting strategy wherein i) the template diethyl chlorophosphate (DCP), (a simulant of organophosphorous nerve agents), is covalently linked to the reactive functional monomer vinyl aniline (VA) during imprinting step followed by noncovalent rebinding and ii) in situ polymerization via single pot synthesis in presence of additional functional monomer, 2‐hydroxyethyl methacrylate (HEMA) and crosslinking monomer, ethylene glycol dimethacrylate (EGDMA) after addition of 2‐nitrophenyl octyl ether (NPOE) and 2,2′‐azobisisobutyronitrile (AIBN) as plasticizer and initiator respectively. The resulting membrane is integrated with a potentiometric transducer while designing a DCP sensor. The fabricated sensor responds over a wider concentration range of 10−6–10−2 M with a lower detection limit of 10−6 M (0.17 ppm). In addition, in situ monolithic membrane based sensor was designed by adopting noncovalent imprinting strategy also. A detailed comparison is made between semicovalent and noncovalent in situ membrane based sensors on the prime sensor performance criteria such as sensitivity, selectivity, working range, response time, reusability and reversibility. Again, the relative merits and demerits of semicovalent vis‐à‐vis noncovalent strategy based in situ monolithic membrane sensors were also highlighted. The probable molecular recognition mechanism is also discussed.

Proapoptotic and Anticarcinogenic Activities of Leviusculoside G from the Starfish Henricia leviuscula and Probable Molecular Mechanism

Proapoptotic and anticarcinogenic properties of leviusculoside G (LSG) isolated from the starfish Henricia leviuscula and a probable mechanism of these effects were investigated in human leukemia HL-60, THP-1, and mouse skin JB6 Cl41 cells, using a variety of assessments, including a cell viability (MTS) assay, flow cytometry, anchorage-independent soft agar assay, luciferase assay, and western-blotting. Application of LSG at nontoxic doses induced apoptosis in cancer cells and decreased cell transformation. This compound exerted its actions, at least in part, through the induction of p53-dependent apoptosis and inhibition of AP-1, NF-κB, and ERKs activities.