Dipeptide IF prevents the effects of hypertension-induced Alzheimer's disease on long-term memory in the cortex of spontaneously hypertensive rats.

Hypertension (HTN) is one of the most prevalent chronic conditions; it can damage blood vessels and rupture blood vessels can trap in small vessels. This blockage can prevent blood flow and oxygen delivery to brain cells and can result in Alzheimer's disease (AD). HTN- and AD-mediated long-time memory loss and its treatment remain poorly understood. Plant-derived natural compounds are alternative solutions for effectively treating diseases without any side effects. This study revealed that bioactive peptides extracted from potato hydrolysis suppress HTN-mediated long-term memory (LTM) loss and cell apoptosis, thus improving memory formation and neuronal cell survival in the spontaneously hypertensive rat (SHR) rat model. SHR rats were treated with bioactive peptide IF (10 mg/kg orally) and angiotensin-converting enzyme inhibitors (5 mg/kg orally). In this study, we evaluated the molecular expression levels of BDNF-, GluR1-, and CREB-mediated markers protein expression in 24-week-old SHR rats. The study result showed that HTN-induced AD regulated long-term memory (LTM) loss and neuronal degeneration in the SHR animals. The bioactive peptide-treated animals showed an elevated level of survival proteins. Bioactive peptide IF activate CREB-mediated downstream proteins to regulate synaptic plasticity and neuronal survival in the SHR rat model.

ß-Catenin overexpression causes an increase in inflammatory cytokines and NF-κB activation in cardiomyocytes.

ß-Catenin has been implicated in various developmental and physiological processes. Defective Wnt signaling can result in different cardiac and vascular abnormalities and is activated under pathological conditions such as inflammation and obesity. In this study, roles of ß-catenin in inflammation in cardiomyocytes were investigated. 10 samples from hearts of patients with acute infarction and 10 from normal ones were collected in order to access roles of ß-catenin in cardiomyocytes. H9c2 cardiomyoblasts and primary neonatal rat cardiomyocytes were transfected with porcine cytomegalovirus (pCMV)-ß-catenin plasmid in order to overexpress ß-catenin. Protein level of ß-catenin protein was increased in human acute infarction tissues compared to ones from normal patients. The transcription factor had increased nuclear localization in cardiomyocytes of the Wistar rats with cardiac hypertension. Furthermore, expression of fibrosis protein markers increased. Protein expression of ß-catenin was increased in human acute infarction inflammatory heart tissues and in hearts of inflammatory obesity rats. After pCMV-ß-catenin plasmid was transfected in a dose-dependent manner, inflammation protein markers, TNF-α and IL-8, were upregulated in hypertensive neonatal rat cardiomyocytes and H9c2 cardiomyoblasts. In addition, overexpression of ß-catenin induced activation and nuclear localization of NF-κB. Therefore, ß-catenin is a potential molecular target for treatment of inflammation and fibrosis in cardiomyocytes.

DNA binding, antioxidant, cytotoxicity (MTT, lactate dehydrogenase, NO), and cellular uptake studies of structurally different nickel(II) thiosemicarbazone complexes: synthesis, spectroscopy, electrochemistry, and X-ray crystallography.

Three new nickel(II) thiosemicarbazone complexes have been synthesized and characterized by analytical, spectral, and single-crystal X-ray diffraction studies. In complex 1, the ligand 2-hydroxy-1-naphthaldehydethiosemicarbazone coordinated as a monobasic tridentate donor, whereas in complexes 2 and 3, the ligands salicylaldehyde-4(N)-ethylthiosemicarbazone and 2-hydroxy-1-naphthaldehyde-4(N)-ethylthiosemicarbazone coordinated as a dibasic tridentate donor. The DNA binding ability of the complexes in calf thymus DNA was explored by absorption and emission titration experiments. The antioxidant property of the new complexes was evaluated to test their free-radical scavenging ability. In vitro cytotoxicity assays were performed for the new complexes in A549 and HepG2 cell lines. The new compounds overcome cisplatin resistance in the A549 cell line and they were also active in the HepG2 cell line. The cellular uptake study showed the accumulation of the complexes in tumor cells depended on the nature of the ligand attached to the nickel ion.

Synthesis, DNA/protein binding and in vitro cytotoxic studies of new palladium metallothiosemicarbazones.

A series of four new thiosemicarbazone complexes of palladium have been synthesized, characterized and evaluated for their DNA/protein binding with CT-DNA and BSA, respectively. The new complexes bound to CT-DNA by intercalation mode and in protein binding studies, the complexes bound to BSA binding mechanism was found as static quenching. Among them the complex 4 had a strong binding affinity with BSA. In addition, in vitro cytotoxic studies were carried out on lung cancer (A549) and liver cancer (HepG2) cell lines and found that the complexes exhibited better activity than their parent thiosemicarbazone analogues. The complex 3 exhibited better activity than other complexes and this fact supported by the increased accumulation of the complexes in to the cancer cells which are evident from inter cellular uptake studies.

Inhibition of HSF2 SUMOylation via MEL18 upregulates IGF-IIR and leads to hypertension-induced cardiac hypertrophy.

Cardiac hypertrophy is a major characteristic of early-stage hypertension-related heart failure. We have found that the insulin-like growth factor receptor II (IGF-IIR) signaling was critical for hypertensive angiotensin II-induced cardiomyocyte hypertrophy and apoptosis. Moreover, this IGF-IIR signaling was elegantly modulated by the heat shock transcription factors (HSFs) during heart failure. However, the detailed mechanism by which HSFs regulates IGF-IIR during hypertension-induced cardiac hypertrophy remains elusive. In this study, we found that heat shock transcription factor 2 (HSF2) activated IGF-IIR to induce cardiac hypertrophy for hypertension-induced heart failure. The transcriptional activity of HSF2 appeared to be primarily mediated by SUMOylation via conjugation with small ubiquitin-like modifier-1 (SUMO-1). The SUMOylation of HSF2 was severely attenuated by MEL18 (also known as polycomb group ring finger 2 or PCGF2) in the heart of spontaneously hypertensive rats (SHR). Inhibition of HSF2 SUMOylation severely induced cardiac hypertrophy via IGF-IIR-mediated signaling in hypertensive rats. Angiotensin II receptor type I blocker (ARB) treatment in spontaneously hypertensive rats restored HSF2 SUMOylation and alleviated the cardiac defects. Thus, our study uncovered a novel MEL18-SUMO-1-HSF2-IGF-IIR pathway in the heart that profoundly influences cardiac hypertrophy for hypertension-induced heart failure.

Data supporting the angiotensin II activates MEL18 to deSUMOylate HSF2 for hypertension-related heart failure.

In association with the published article "Inhibition of HSF2 SUMOylation via MEL18 upregulates IGF-IIR and leads to hypertension-induced cardiac hypertrophy" (Huang et al., 2017) [1], this data article contains information about deSUMOylation of HSF2 on lysine 82 on angiotensin II (ANG II) -induced cardiac hypertrophy, which is mediated by MEL18. Isolated adult human whole heart tissue showed MEL18-mediated HSF2-IGF-IIR pathway is upregulated in hypertension human heart, compared to health human heart.

Potential phytoestrogen alternatives exert cardio-protective mechanisms via estrogen receptors.

The 17 beta-estradiol (E2) is a sex hormone that is most abundant and most active estrogen in premenopausal women. The importance of E2 in providing cardioprotection and reducing the occurrence of heart disease in women of reproductive age has been well recognized. There are three subtype of estrogen receptors (ERs), including ERα, ERß and GPR30 have been identified and accumulating evidence reveal their roles on E2-mediated genomic and nongenomic pathway in cardiomyocytes against various cardiac insults. In this review, we focus on the estrogen and ERs mediated signaling pathways in cardiomyocytes that determines cardio-protection against various stresses and further discuss the clinical implication of ERs and phytoestrogens. Further we provide some insights on phytoeostrogens which may play as alternatives in estrogen replacement therapies.

Effect of fish oil pretreatment on isoproterenol-induced changes in myocardial membrane phospholipids.

OBJECTIVE: In the present study, the protective effect of fish oil treatment on the fatty acid composition in isoproterenol (IPH)-induced myocardial infarction was studied in male albino Wistar rats. METHODS: Rats were injected for 2 consecutive days with IPH (60 mg/kg body weight) at 24-h intervals to induce myocardial infarction. Fish oil was administered orally at a dose of 0.05 mL/d for 45 d, after which serum and heart tissue were assayed for lipid profile, lipoprotein changes, and myocardial membrane phospholipid fatty acid composition. RESULTS: Biochemical assessment of myocardial infarction was done by measuring the activities of creatinine kinase and lactate dehydrogenase, which were significantly elevated in the rats administered with IPH. Further, the administration of IPH modified the fatty acid composition and analysis of fatty acids showed there was an increase in the omega-3/omega-6 ratio in phospholipid pool. In addition, increased levels of total cholesterol, free cholesterol, ester cholesterol, phospholipids, triacylglycerols and free fatty acid was observed in serum and heart tissue of IPH-induced rats. The fish oil treatment for a period of 45 d decreased the levels of cardiac markers (creatinine kinase and lactate dehydrogenase) and reversed the biochemical lesions induced by IPH. CONCLUSION: Our study suggests that fish oil treatment has a hypolipidemic effect and has potential use in the treatment of myocardial infarction.

Biological evaluation of new nickel(II) metallates: Synthesis, DNA/protein binding and mitochondrial mediated apoptosis in human lung cancer cells (A549) via ROS hypergeneration and depletion of cellular antioxidant pool.

A series of novel nickel(II) thiosemicarbazone complexes(1-4) have been prepared and characterized by various spectral, analytical techniques and X-ray crystallography. Further, their efficacy to interact with CT-DNA/BSA has been explored. From the binding studies, it is inferred that complex 4 found to be more active than other complexes. The complexes bound with CT-DNA by intercalation mode. Moreover, static quenching was observed for their interaction with BSA. The new complexes were tested for their in vitro cytotoxicity against human lung adenocarcinoma (A549) cell line. The results showed that the new complexes exhibited significant degree of cytotoxicity at given experimental condition. Further, the results of LDH and NO release supported the cytotoxic nature of the complexes. The observed cytotoxicity of the complexes may be routed through ROS-hypergeneration and lipid-peroxidation with subsequent depletion of cellular antioxidant pool (GSH, SOD, CAT, GPx and GST) resulted in the reduction of mitochondrial-membrane potential, caspase-3 activation and DNA fragmentation. Thus, the data from the present study disclose that the complexes could induce apoptosis in A549 cells through mitochondrial mediated fashion and inhibited the migration of lung cancer cells and by metastasis.

One pot synthesis of structurally different mono and dimeric Ni(II) thiosemicarbazone complexes and N-arylation on a coordinated ligand: a comparative biological study.

One pot synthesis of three structurally different Ni(II) thiosemicarbazone complexes 1, 2 and 3 were obtained from the reaction between [NiCl(2)(PPh(3))(2)], 1,2-bis(diphenylphosphino)ethane, and [H(2)-(Sal-tsc)]. The obtained products were characterized by various spectral and analytical techniques. From the X-ray crystallographic analysis, an unexpected N-arylation on the coordinated salicylaldehydethiosemicarbazone was found in complex 2. The comparative biological evolutions such as DNA/protein binding, antioxidant, cytotoxicity (MTT, LDH, and NO) and cellular uptake studies have been examined for [Ni(Sal-tsc)(PPh(3))] (1) and [(Ni(Sal-tsc))(2)(µ-dppe)] (3). When comparing the cytotoxicity of the complexes, 1 exhibited higher activity than 2 and 3 and by comparing with standard cis-platin, both of them were found to exhibit better activity under identical conditions.

Influence of terminal substitution on structural, DNA, protein binding, anticancer and antibacterial activities of palladium(II) complexes containing 3-methoxy salicylaldehyde-4(N) substituted thiosemicarbazones.

The variable chelating behavior of 3-methoxysalicylaldehyde-4(N)-substituted thiosemicarbazones was observed in equimolar reactions with [PdCl(2)(PPh(3))(2)]. The new complexes were characterized by various analytical, spectroscopic techniques (mass, (1)H-NMR, absorption, IR). All the new complexes were structurally characterized by single crystal X-ray diffraction. Crystallographic results showed that the ligands H(2)L(1) and H(2)L(4) are coordinated as binegative tridentate ONS donor ligands in the complexes 1 and 4 by forming six and five member rings. However, the ligands H(2)L(2) and H(2)L(3) bound to palladium in 2 and 3 as uninegative bidentate NS donors by forming a five member chelate ring. From this study, it was found that the substitution on terminal 4(N)-nitrogen may have an influence on the chelating ability of thiosemicarbazone. The presence of hydrogen bonding in 2 and 3 might be responsible for preventing the coordination of phenolic oxygen to the metal ion. The interaction of the complexes with calf-thymus DNA (CT-DNA) has been explored by absorption and emission titration methods. Based on the observations, an electrostatic binding mode of DNA has been proposed. The protein binding studies were monitored by quenching of tryptophan and tyrosine residues in the presence of complexes using Lysozyme as model protein. Antibacterial activity studies of the complexes have been screened against pathogenic bacteria such as Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa. MIC50 values of the complexes showed that they exhibited significant activity against the pathogens and among them, 3 exhibited higher activity. Further, anticancer activity of the complexes on the lung cancer cell line A549 has also been studied.

Protective effect of gallic acid against lindane induced toxicity in experimental rats.

Lindane is an organochlorine pesticide that persists in the environment, bioaccumulate through food chain and has a risk of causing adverse effects to human health and the environment. It induces cell damage by producing free radicals and reactive oxygen species. The aim of the present study is to investigate the protective effect of gallic acid (a plant derived polyphenol) against lindane induced hepatic and renal toxicity in rats. Liver damage was assessed by hepatic serum marker enzymes like SGOT, SGPT and ALP and histopathological observation. Renal damage was observed by histopathological examination and serum markers like creatinine and urea. Treatment with lindane increased the levels of lipid peroxidation, serum marker enzyme activity with a concomitant decrease in GSH, CAT, SOD, GPx and GST. Histological alterations were also observed in kidney and liver tissue with lindane treatment. Co-treatment of gallic acid significantly prevented the lindane induced alterations in kidney and liver tissues with a decrease in LPO, serum marker enzyme activity and a significant increase in antioxidant levels. These results suggest that gallic acid has protective effect over lindane induced oxidative damage in rat liver and kidney.