Flavonoid-metal ion Complexes as Potent Anticancer metallodrugs: A comprehensive Review.

BACKGROUND: Flavonoids and their analogous are mainly found in pink lady apples, green and black tea (catechins), celery and red peppers, onions, broccoli and spinach, berries, cherries, soybean, citrus fruits, and fungi. The different derivatives of flavonoids belonging to polyphenolic compounds such as 3,4',5,7-Tetrahydroxyflavylium (pelargonidin), 2-(3,4-Dihydroxyphenyl)chromenylium-3,5,7-triol (cyanidin), 3,3',4',5,5',7-Hexahydroxyflavylium (delphinidin), 3,3',4',5,7-Pentahydroxy-5'-methoxyflavylium (petunidin), and 3,4',5,7-Tetrahydroxy-3',5'-dimethoxyflavylium (malvidin) can act as good chelating agents for metal-chelate complex formation. These flavonoid-metal complexes have been reported to have various biomedical and pharmacological activities. OBJECTIVE: Flavonoid-metal ion complexes display a broad spectrum of biological properties such as antioxidant, anti-inflammatory, anti-allergic, antiviral, anticarcinogenic, and cytotoxic activity. The literature survey showed that flavonoid metal complexes have potential therapeutic properties against various cancerous cells. The objective is to gain insight into the current perspective and development of novel anticancer metallodrug drugs. METHODS: The flavonoid-metal ion complexes can be prepared by reacting flavonoid ligand with appropriate metal salt in aqueous or alcoholic reaction medium under stirring or refluxing conditions. In this review article, the various reported methods for the synthesis of flavonoid-metal complexes have been included. The utility of synthetic methods for flavonoid-metal complexes will support the discovery of novel therapeutic drugs. RESULTS: In this review study, short libraries of flavonoid-metal ion complexes were studied as potential anticancer agents against various human cancer cell lines. The review report reveals that metal ions such as Fe, Co, Ni, Cu, Zn, Rh, Ru, Ga, Ba, Sn etc., when binding to flavonoid ligands, enhance the anticancer activity compared to free ligands. This review study covered some important literature surveys for the last two decades. CONCLUSION: It has been concluded that flavonoid metal complexes have been associated with a wide range of biological properties that could be noteworthy in the medicinal field. Therefore, to develop a new anticancer drug, it is essential to determine the primordial interaction drug with DNA under physiological or anatomical conditions. The study of numerous flavonoid metal complexes mentioned in this paper could be the future treatment against various cancerous diseases.

Description of Stenotrophomonas sepilia sp. nov., isolated from blood culture of a hospitalized patient as a new member of Stenotrophomonas maltophilia complex.

Stenotrophomonas sepilia strain SM16975 (= JCM 32102; = KCTC 62052) is a new species isolated from the blood culture of a hospitalized patient. The biochemical characterization, phenotypic criteria, phylogenomic reconstruction, and genomic analysis were carried out to differentiate it from its phylogenetic neighbours, establishing novel species status in the genus Stenotrophomonas and within Stenotrophomonas maltophilia complex (Smc).

APTES monolayer coverage on self-assembled magnetic nanospheres for controlled release of anticancer drug Nintedanib.

The use of an appropriate delivery system capable of protecting, translocating, and selectively releasing therapeutic moieties to desired sites can promote the efficacy of an active compound. In this work, we have developed a nanoformulation which preserves its magnetization to load a model anticancerous drug and to explore the controlled release of the drug in a cancerous environment. For the preparation of the nanoformulation, self-assembled magnetic nanospheres (MNS) made of superparamagnetic iron oxide nanoparticles were grafted with a monolayer of (3-aminopropyl)triethoxysilane (APTES). A direct functionalization strategy was used to avoid the loss of the MNS magnetization. The successful preparation of the nanoformulation was validated by structural, microstructural, and magnetic investigations. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) were used to establish the presence of APTES on the MNS surface. The amine content quantified by a ninhydrin assay revealed the monolayer coverage of APTES over MNS. The monolayer coverage of APTES reduced only negligibly the saturation magnetization from 77 emu/g (for MNS) to 74 emu/g (for MNS-APTES). Detailed investigations of the thermoremanent magnetization were carried out to assess the superparamagnetism in the MNS. To make the nanoformulation pH-responsive, the anticancerous drug Nintedanib (NTD) was conjugated with MNS-APTES through the acid liable imine bond. At pH 5.5, which mimics a cancerous environment, a controlled release of 85% in 48 h was observed. On the other hand, prolonged release of NTD was found at physiological conditions (i.e., pH 7.4). In vitro cytotoxicity study showed dose-dependent activity of MNS-APTES-NTD for human lung cancer cells L-132. About 75% reduction in cellular viability for a 100 µg/mL concentration of nanoformulation was observed. The nanoformulation designed using MNS and monolayer coverage of APTES has potential in cancer therapy as well as in other nanobiological applications.

Effect of intensifying additives on the degradation of thiamethoxam using ultrasound cavitation.

The present study has investigated the degradation of thiamethoxam using ultrasound cavitation (US) operated at a frequency of 20 kHz and its combination with intensifying additives viz. hydrogen peroxide, Fenton and photo-Fenton reagent. At the outset, the performance of US (20 kHz) has been maximised by the optimization of process parameters. Highest rate of degradation of thiamethoxam was observed at the optimum ultrasonic power density of 0.22 W/mL, thiamethoxam concentration of 10 ppm and the pH of 2. The established optimum values of operating parameters were used further in case of combined treatment approaches. The effect of concentration of H2O2 on the rate of degradation of thiamethoxam in the case of US + H2O2 process has confirmed the existence of optimum concentration of H2O2 with the ratio of thiamethoxam: H2O2 as 1:10. US + Fenton process indicated the optimal molar ratio of FeSO4·7H2O:H2O2 as 1:15. The combined processes of US + H2O2, US + Fenton and US + photo-Fenton have resulted in the extent of degradation of 20.47 ± 0.61%, 34.41 ± 1.03% and 85.17 ± 2.56% respectively after 45 min. of operation. These combined processes lead to the synergistic index of 2.04 ± 0.06, 2.26 ± 0.07 and 2.42 ± 0.07 in case of US + H2O2, US + Fenton and US + photo-Fenton processes respectively over only US/stirring treatment with the additive. Additionally, the extent of mineralization and the energy efficiency of individual and combined processes have been compared. US + photo-Fenton process has been found to be the best strategy for effective degradation of thiamethoxam with a significant intensification benefit. The by-products formed during the ultrasonic degradation of thiamethoxam have been identified by using LC-MS/MS analysis.

Pulsed laser deposited CoFe2O4 thin films as supercapacitor electrodes.

The influence of the substrate temperature on pulsed laser deposited (PLD) CoFe2O4 thin films for supercapacitor electrodes was thoroughly investigated. X-ray diffractometry and Raman spectroscopic analyses confirmed the formation of CoFe2O4 phase for films deposited at a substrate temperature of 450 °C. Topography and surface smoothness was measured using atomic force microscopy. We observed that the films deposited at room temperature showed improved electrochemical performance and supercapacitive properties compared to those of films deposited at 450 °C. Specific capacitances of about 777.4 F g-1 and 258.5 F g-1 were obtained for electrodes deposited at RT and 450 °C, respectively, at 0.5 mA cm-2 current density. The CoFe2O4 films deposited at room temperature exhibited an excellent power density (3277 W kg-1) and energy density (17 W h kg-1). Using electrochemical impedance spectroscopy, the series resistance and charge transfer resistance were found to be 1.1 Ω and 1.5 Ω, respectively. The cyclic stability was increased up to 125% after 1500 cycles due to the increasing electroactive surface of CoFe2O4 along with the fast electron and ion transport at the surface.

Monolayer grafting of aminosilane on magnetic nanoparticles: An efficient approach for targeted drug delivery system.

Magnetic nanoparticles (MNPs) with higher magnetization are highly desirable for targeted drug delivery (TDD) systems, as it helps accumulation of drug at the target site. However, functionalization of MNPs for drug binding reduces the magnetization which affects the efficacy of TDD. Herein we report direct functionalization of MNPs with (3-Aminopropyl)triethoxysilane (APTES) which preserves the magnetization. Grafting density estimated by TGA and BET analysis showed monolayer grafting of APTES on MNP surface. MNPs were comprehensively characterized by XRD, HR-TEM, SQUID-VSM and FTIR. Anti-cancerous drug telmisartan (TEL) was loaded on monolayer APTES grafted MNPs. In-vitro controlled drug release and cytotoxicity study on PC-3 human prostate cancer cell line of TEL conjugated MNPs are also discussed. This functionalization strategy can be extended to other biomedical applications where higher magnetization is desired.

Magnetic nanoparticle decorated graphene based electrochemical nanobiosensor for H2O2 sensing using HRP.

To utilize synergetic effect of graphene's higher conductivity and magnetic nanoparticles biocompatibility, an electrochemical nanobiosensor is constructed based on magnetic nanoparticle decorated graphene (MRGO) using Horseradish peroxidase (HRP) for H2O2 sensing. Sensors based on magnetic nanoparticles (MNP) and reduced graphene oxide (RGO) are studied for comparison. MNP, RGO and MRGO were characterized by X-ray diffraction (XRD), Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). XRD studies have confirmed successful synthesis of Fe3O4 MNPs, RGO and MRGO. TEM micrographs revealed uniform decoration of MNPs on graphene. FTIR confirmed the immobilization of HRP on MNP, RGO and MRGO. The MRGO based sensor exhibited higher sensitivity (48.08 µA µM-1 cm-2) compared to MNP (39.08 µA µM-1 cm-2) and RGO (41.08 µA µM-1 cm-2) based biosensors.

Immobilization of invertase on chitosan coated γ-Fe2O3 magnetic nanoparticles to facilitate magnetic separation.

Industrially important invertase enzyme was immobilized on chitosan coated sol gel derived γ-Fe2O3 magnetic nanoparticles (MNPs) to enable it for repetitive use by magnetic separation. MNPs were characterized by X-ray diffraction (XRD), dynamic light scattering (DLS), field emission scanning electron microscope (FE-SEM), Fourier transform infrared (FTIR) spectrometer and magnetic measurements. FTIR studies confirmed successful immobilization of invertase on MNPs. The ability to convert sucrose into invert syrup was enhanced in immobilized invertase compared to that of free enzyme. Further it was found that invertase immobilized on MNPs (IIMNPs) were more stable at varying pH and temperature conditions. Magnetic separation technique was successfully employed for reuse of the IIMNPs for 20 times without significant loss of activity.

TiO2 based nanostructured memristor for RRAM and neuromorphic applications: a simulation approach.

We report simulation of nanostructured memristor device using piecewise linear and nonlinear window functions for RRAM and neuromorphic applications. The linear drift model of memristor has been exploited for the simulation purpose with the linear and non-linear window function as the mathematical and scripting basis. The results evidences that the piecewise linear window function can aptly simulate the memristor characteristics pertaining to RRAM application. However, the nonlinear window function could exhibit the nonlinear phenomenon in simulation only at the lower magnitude of control parameter. This has motivated us to propose a new nonlinear window function for emulating the simulation model of the memristor. Interestingly, the proposed window function is scalable up to f(x) = 1 and exhibits the nonlinear behavior at higher magnitude of control parameter. Moreover, the simulation results of proposed nonlinear window function are encouraging and reveals the smooth nonlinear change from LRS to HRS and vice versa and therefore useful for the neuromorphic applications.

Identification and characterization of intestinal lactobacilli strains capable of degrading immunotoxic peptides present in gluten.

AIM: Identify and characterize bacteria from the proximal gastrointestinal tract of pigs capable of degrading immunogenic gluten peptides. METHODS AND RESULTS: Bacteria were cultured from the small intestine of pigs fed a 20% gluten diet and from an enrichment media with the 18-mer peptide LQLQPFPQPQLPYPQPQL. Isolates were screened for the production of specialized proteolytic enzymes and the ability to degrade and remove metastable peptides from α-gliadin (16-mer and 33-mer) and ω-gliadin (17-mer), with established roles in the aetiology of coeliac disease. Degradation was determined by ELISA and mass spectrometry (UHPLC-MS/MS in MRM mode), and hydrolysis fragments were characterized by LC-MS/MS. Four strains from the species Lactobacillus ruminis, Lactobacillus johnsonii, Lactobacillus amylovorus and Lactobacillus salivarius showed the highest peptide-degrading activities. Strains displayed different degradation rates and cleavage patterns that resulted in reduction but not complete removal of immunotoxic epitopes. CONCLUSIONS: We employed a unique enrichment process to select for bacteria adapted to the conditions of the proximal gastrointestinal tract with the ability to partially detoxify well-characterized peptides involved in coeliac disease. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a basis for the selection of Lactobacillus strains for probiotic applications aimed to reduce epitope-containing gluten peptides before reaching the epithelium of the small intestine of patients with coeliac disease.

A rare case of antepartum posterior reversible encephalopathy syndrome.

Pre-eclampsia and eclampsia are well-known causative factors of posterior reversible encephalopathy syndrome (PRES). There are only a few reported cases of antepartum PRES. We report a 25-year-old primigravid woman who presented with eight months of amenorrhoea and an abrupt onset of eclampsia associated with a history of a fall. A computed tomography scan ruled out intracranial haemorrhage and PRES was diagnosed. She responded well to supportive care, labour was induced and maternal and neonatal outcomes were good. Antepartum PRES poses different challenges to those of PRES in non-obstetric or postpartum patients, because of the additional management aspects required to ensure foetal wellbeing. We were posed with a difficult decision about the disadvantages of caesarean section versus those of vaginal delivery in our patient.

Antihyperglycemic activity and inhibition of advanced glycation end product formation by Cuminum cyminum in streptozotocin induced diabetic rats.

Cuminum cyminum is widely used as a spice in many countries. The aim of the present study was to investigate the effect of methanolic extract of seeds of C. cyminum (CC) on diabetes, oxidative stress and formation of advanced glycated end products (AGE) and obtain comparison with glibenclamide. In vitro studies indicated that CC inhibited free radicals and AGE formation. Treatment of streptozotocin-diabetic rats with CC and glibenclamide for 28 days caused a reduction in blood glucose, glycosylated hemoglobin, creatinine, blood urea nitrogen and improved serum insulin and glycogen (liver and skeletal muscle) content when compared to diabetic control rats. Significant reduction in renal oxidative stress and AGE was observed with CC when compared to diabetic control and glibenclamide. CC and glibenclamide improved antioxidant status in kidney and pancreas of diabetic rats. Diabetic rats showed increase in rat tail tendon collagen, glycated collagen, collagen linked fluorescence and reduction in pepsin digestion. Treatment with CC significantly improved these parameters when compared to diabetic control and glibenclamide group. Though the antidiabetic effect of CC was comparable to glibenclamide it had better effect in controlling oxidative stress and inhibiting the AGE formation, which are implicated in the pathogenesis of diabetic microvascular complications.

Role of ataxia telangiectasia mutated in insulin signalling of muscle-derived cell lines and mouse soleus.

AIM: Ataxia telangiectasia mutated (ATM) reportedly plays a role in insulin-stimulated activation of Akt in some cell types but not in others. The role of ATM in insulin signalling has not been firmly resolved for skeletal muscle cells, for which Akt phosphorylation is a pivotal step in stimulation of glucose transport. Accordingly, our aim was to determine the role of ATM in insulin effects for cell lines derived from skeletal muscle and for skeletal muscle. METHODS: We examined insulin effects in L6 myotubes, mouse soleus, C2C12 myotubes and differentiated rhabdomyosarcoma (RD) cells in the presence and absence of a low concentration (1 microm) of the ATM inhibitor KU55933. We also compared insulin signalling in C2C12 cells expressing shRNA against ATM and control cell lines (empty vector; cells expressing non-targeting shRNA). RESULTS: In L6 myotubes and mouse soleus muscle, KU55933 inhibited insulin-stimulated phosphorylation of the 160 kDa substrate of Akt (AS160) despite no effect on Akt. In contrast, KU55933 prevented insulin-stimulated Akt phosphorylation in C2C12 myotubes. Furthermore, C2C12 myotubes expressing shRNA against ATM displayed reduced insulin-stimulated Akt phosphorylation compared to controls. KU55933 also decreased insulin-stimulated Akt phosphorylation in differentiated RD cells. CONCLUSION: These model-dependent differences in the role of ATM in insulin action demonstrate a role of ATM in insulin-stimulated phosphorylation of Akt (in C2C12 and RD cells) but also allow the elucidation of a novel, Akt-independent role of ATM (in L6 myotubes and mouse soleus, at the level of AS160) in insulin signalling.

Magnetotransport and structural properties of nanocrystalline FeAgAl thin films.

Structural and magnetotransport properties of metallic Fe(x)Ag(y)Al(z) nanogranular thin films were studied. These films with several compositions were prepared by dc magnetron sputtering. X-ray diffraction (XRD) measurements carried out on the samples show only Ag(111) peaks. The d-spacings determined from the Ag(111) peaks are smaller than the standard value for bulk Ag indicating a partial substitution of Fe and Al atoms in Ag matrix. Transmission electron diffraction (TEM) patterns show a number of Ag rings. Both XRD and TEM studies did not reveal any diffraction peaks due to Fe or Al. The average particle size determined from the TEM micrograph is 5.9 nm. This value is in good agreement with the grain size determined from the XRD patterns for the Al substituted samples. The MR was found to increase for smaller Al concentration and it decreases with further increase in Al content. In the samples investigated magnetoresistance ratio reaches a maximum value of about 4.5% for the Fe27Ag63Al10 film.

Structure, microstructure, and giant magnetoresistance in nanogranular FeAgNi thin films.

Structural, microstructural, and magnetoresistive properties of metallic Fe(x)Ag(y)Ni(z) granular thin films were studied. These films with several compositions were prepared by dc magnetron sputtering. X-ray diffraction (XRD) measurements carried out on the samples show only Ag(111) peaks. The d-spacings determined from the Ag(111) peaks are smaller than the standard value for bulk Ag indicating a partial intermixing of Fe and Ni atoms in Ag. The diffraction pattern obtained using Transmission electron microscope (TEM) shows a number of Ag rings. Both XRD and TEM studies did not reveal any diffraction peaks due to Fe or Ni. The average particle size determined from the TEM micrograph is 5.5 nm whereas that determined from the XRD patterns is always higher. The magnetoresistance ratio for all the samples lies in the range 3 to 4.3%, except for a sample.

Malonyl coenzyme A affects insulin-stimulated glucose transport in myotubes.

There seems to be an association between increased concentrations of malonyl coenzyme A (malonyl CoA) in skeletal muscle and diabetes and/or insulin resistance. The purpose of the current study was to test the hypothesis that treatments designed to manipulate malonyl CoA concentrations would affect insulin-stimulated glucose transport in cultured C2C12 myotubes. We assessed glucose transport after polyamine-mediated delivery of malonyl CoA to myotubes, after incubation with dichloroacetate (which reportedly increases malonyl CoA levels), or after exposure of myotubes to 2-bromopalmitate, a carnitine palmitoyl transferase I inhibitor. All three of these treatments prevented stimulation of glucose transport by insulin. We also assayed glucose transport after 30 min of inhibition of acetyl coenzyme A carboxylase (ACC), the enzyme which catalyzes the production of malonyl CoA. Three unrelated ACC inhibitors (diclofop, clethodim, and Pfizer CP-640186) all enhanced insulin-stimulated glucose transport. However, none of the treatments designed to manipulate malonyl CoA concentrations altered markers of proximal insulin signaling through Akt. The findings support the hypothesis that acute changes in malonyl CoA concentrations affect insulin action in muscle cells but suggest that the effects do not involve alterations in proximal insulin signaling.

Mania in hiv infection.

Mania in HIV infected individuals is an uncommon clinical presentation. It can, however, complicate any stage of the HIV infection. We herewith report a set of three case reports of patients with HIV infection who developed manic episodes. The cases highlight some aspects of the plausible relationship between HIV infection and mania. HIV infection could be revealed by manic episode, it could itself also be associated with increased cycling in bipolar patients. Mania could be secondary to HIV or zidovudine therapy (though the etiological role of the latter is as yet unclear). Mania could also occur as a reaction to awareness to having HIV infection. These relationships are important for both the physician and the psychiatrist as they have important therapeutic and prognostic implications.

Processing of commercial peanut cake into food-grade meal and its utilization in preparation of cookies.

The commercial cake produced during expeller pressing of peanuts was extracted with n-hexane, and 80% ethanol followed by sieving through 80 mesh, to remove residual oil, pigments, bitter taste and fibrous material. The processed meal exhibited comparable composition with defatted peanut flour prepared in the laboratory by solvent extraction of full-fat peanut meal. However, the processed cake meal exhibited low methionine content and in vitro protein digestibility as compared with defatted peanut flour. The processed cake meal can be blended with wheat flour to the extent of 10% (w/w) to prepare acceptable cookies with improved protein and mineral contents.