Computational investigation of 2, 4-Di Tert Butyl Phenol as alpha amylase inhibitor isolated from Coccinia grandis (L.) Voigt using molecular docking, and ADMET parameters.

INTRODUCTION: Diabetes Mellitus is the metabolic disorder most prevalent globally, accounting for a substantial morbidity rate. The conventional drugs available for the management of diabetes are either expensive or lack the required efficacy. The purpose of this research is to isolate and characterize an active phytoconstituent from Coccinia grandis and assess its anti-diabetic properties. METHODS AND MATERIALS: Stems of Coccinia grandis are subjected to successive extraction and isolation. The isolated compound by column chromatography was characterized by FTIR (fourier-transform infrared), 1 H NMR (proton nuclear magnetic resonance), and Mass spectroscopy. The antidiabetic potential of the isolated compound was evaluated by in-vitro alpha-amylase inhibitory activity. Further, the compound was subjected to molecular docking studies to study its interaction with the human pancreatic alpha-amylase (Molegro Virtual Docker) as well to determine the pharmacokinetic and toxicity profile using computational techniques (OSIRIS property explorer, Swiss ADME, pkCSM, and PreADMET). RESULTS: The characterization of the compound suggests the structure to be 2,4-ditertiary butyl phenol. The in-vitro alpha-amylase inhibitory study indicated a concentration-dependent inhibition and the IC50 (median lethal dose) value of the isolated compound was found to be 64.36 µg/ml. The docking study with the A chain of receptor 5EMY yielded a favorable docking score of -81.48 Kcal mol-1, suggesting that the compound binds to the receptor with high affinity through electrostatic, hydrophobic, and hydrogen bonds. Furthermore, the silico ADME analysis of the compound revealed improved metabolism, a skin permeability of -3.87 cm/s, gastrointestinal absorption of 95.48 %, and a total clearance of 0.984 log ml min-1 kg-1. In silico toxicity analysis also predicted cutaneous irritations but no carcinogenicity, mutagenicity, or hepatotoxicity. CONCLUSION: The data suggested that the isolated compound (2, 4-tertiary butyl phenol) has the potential to inhibit the alpha-amylase activity and possess optimal ADME properties as well as tolerable side effects.

Antibacterial Activity of CdTe/ZnS Quantum Dot-ß Lactum Antibiotic Conjugates.

ß-Lactum antibiotics are broad class of antibiotics which kills bacteria by inhibiting the formation of peptidoglycan that constitutes the bacterial cell wall. The resistance that develops in bacteria for antibiotics led the scientific world to think about the future aspects for modifying the way through which antibiotics are acted on the bacteria and become lethal for them. In this consequence, the potential of latest marketed antibiotics e.g. Amoxiciline (I), ceftazidim (II) have been evaluated after being conjugated with quantum dots. The surface of quantum dots has been conjugated with antibiotics by carbodiimide coupling with the help of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as conjugating agent between antibiotic and functionalized quantum dots. The antibacterial properties of QD-conjugated antibiotics have been determined by disc diffusion assay. The potency of QD-conjugated antibiotics has been estimated by determining their MIC50 for the selected strain of Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. Minimum inhibitory concentration study, minimum bactericidal concentration and growth pattern analysis revealed that QD-antibiotic conjugates showed slightly more prospective than pure native antibiotics against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria.

Re-evaluation of umbilical cord coiling index in adverse pregnancy outcome - Does it have role in obstetric management?

Introduction: The placenta with the umbilical cord is a vital link between the mother and fetus. Umbilical cord supplies water, nutrients and oxygen from the mother to the fetus. The most unique character of the umbilical cord is its coiling, where the contents of the cord course in a coiled helical fashion. The umbilical coiling index(UCI) can be measured antenatally using ultrasonography. In the present study we have attempted to assess the UCI antenatally by ultrasound screening and correlate abnormal antenatal UCI with the adverse maternal and neonatal outcome of pregnancy. Aims: To study umbilical coiling index ultrasonographically and to correlate it with pregnancy outcome. Methodology: 150 antenatal cases in the second trimester of pregnancy between 22 and 28weeks of gestation attending the outpatient department were included for the study in a continuous manner and subjected to antenatal UCI measurement. The cases were followed up till delivery and various factors were noted. Results: We confirmed that maternal medical comorbidities ( gestational hypertension and anemia) have a significant correlation with abnormal umbilical cord coiling index, either hyper-coiling or hypo-coiling or both.Some studies have shown a particular adverse effect being manifested in both hypo and hypercoiling. In the present study significant correlation of abnormal coiling has been found with only anaemia and hypertension in pregnancy. The question, therefore, arises:"Does abnormal UCI have any significant role in prediction of adverse outcome in pregnancy or is it just a random association?" This study does not reflect any significant role of abnormal UCI in the prediction of adverse perinatal outcome. Hence efforts to monitor UCI in the antenatal period may not have any justification in the present scenario. The latest edition of William's Obstetrics also makes a similar comment. A population based larger study to generate cut offs for hypo and hyper coiling and finding any association between abnormal coiling and perinatal outcome may throw more light on the utility of UCI as a predictor of adverse outcome in pregnancy.

Predictors of disease severity in COVID-19 associated mucormycosis: impact of HbA1C levels, time lag to mucormycosis onset, and radiologic patterns of paranasal sinuses and spaces involvement.

BACKGROUND: Identifying early predictors of severe Covid-19 associated mucormycosis (CAM) can help improve management and treatment outcomes. OBJECTIVES: Primary: To identify clinical and radiological predictors of disease severity in CAM. Secondary: To describe patterns of central nervous system (CNS) involvement in CAM. METHODS: A total of 71 patients with CAM were included in the study. Based on the anatomical extent of involvement on MRI, patients were divided into three groups: Sinus (paranasal sinuses), Orbit (orbital spread), and CNS (CNS spread). Clinical parameters and radiological patterns of involvement of sinuses and extra sinus spaces were studied between the three groups. Patterns of CNS involvement were also described. RESULTS: A shorter time lag between COVID-19 infection and CAM, as well as high HbA1C levels, were found to be associated with severe disease. Involvement of the sphenoid, ethmoid and frontal sinuses, T1 hyperintense signal in the sphenoid, as well as bony involvement of the sphenoid sinus, were significantly associated with severe disease. Extra-sinus spread into pre/retroantral space, pterygopalatine fossa, and masticator spaces were also significantly associated with a severe disease course. The most common pattern of CNS spread was cavernous sinus involvement, followed by pachymeningeal spread and cranial nerve involvement. CONCLUSION: Early identification of the above-described predictors in patients presenting with CAM can help detect those at risk for developing severe disease. A longer duration of amphotericin, combined with a more aggressive surgical approach in selected cases, may lead to better long-term outcomes.

Evaluation of paediatric pulmonary vein stenosis by cardiac CT angiography: a comparative study with transthoracic echocardiography and catheter angiogram.

AIM: To compare prospective electrocardiogram (ECG)-gated cardiac computed tomographic angiography (CCTA) with transthoracic echocardiography (TTE) and cardiac catheter angiography (CCA) for paediatric pulmonary vein (PV) stenosis. MATERIALS AND METHODS: Retrospective chart review was undertaken of all patients who underwent CCTA for PV evaluation over a 4-year period. Patient demographics, findings of CCTA, TTE, and CCA, as well as interventions performed, were recorded for each PV. RESULTS: Thirty-five patients were included (23 male patients). All patients had a prior TTE with time interval between TTE and CCTA ranging from 0 to 90 days. CCTA detected 92 abnormalities in 32 patients. TTE missed 16 PV abnormalities (16/92, 17%), detected 37 abnormalities with certainty (37/92, 40%), and was suggestive in 39 abnormalities (39/92, 42%). CCTA was negative for PV abnormalities when TTE was positive or suspicious in three patients. Nineteen patients underwent CCA (18 patients with 52 abnormalities and one patient with normal PV), confirming CCTA findings. Thirty-nine were treated with angioplasty/stenting (39/52,75%). Failed recanalisation occurred in three PVs (3/52, 6%) and no intervention was attempted for the rest as the gradient was not significant (10/52,19%). Nine patients underwent surgical repair (26/92, 28%). Five patients (14/92, 15%) were managed with no intervention based on CCTA findings and poor clinical prognosis. CONCLUSIONS: CCTA plays an important role in detecting paediatric PV stenosis and identifies additional findings compared to TTE that have direct surgical/interventional implications. CCTA complements TTE in imaging these patients and helps guide management.

Knowledge, attitude and practices among sanitation workers regarding SARS-CoV-2 prevention - A cross-sectional study.

Aim: : To evaluate knowledge, attitude and practices among sanitation workers regarding SARS-CoV-2 prevention during hospital waste management. Materials and Methods: A cross-sectional study was conducted among 426 sanitation workers using an interviewer-administered questionnaire to assess the knowledge, attitude and practices of the study participants. The unpaired t-test and Spearman's correlation were used to find the mean difference and correlation among different study variables. Statistical significance was set at 5% (confidence interval 95%). Results: The mean knowledge score of the participants was found to be 7.15 ± 2.02. About 93.7% of the participants had good knowledge about COVID-19. About 64.3% of the participants strongly agreed that COVID-19 is a life-threatening disease. Regarding practices, a majority reported (69.7%) that they washed hands frequently using water and soap. A significant positive correlation was found between knowledge, attitude, practices and education, indicating a favourable work environment in hospital settings. Conclusion: More than half of the sanitation workers and housekeeping staff had adequate knowledge of COVID-19, and their attitudes were found to be favourable. They also had satisfactory practices, which may be a result of the prompt training and sensitization of sanitation workers by the authorities. Clinical Relevance: Sanitation workers come under the essential services category and their knowledge, attitude and practices needed to be assessed and updated in the concerned area for their protection and better management of biomedical waste, especially in the current pandemic situation.

Defining requirements for integrating information between design, manufacturing, and inspection.

Industry desires a digital thread of information that aligns as-designed, as-planned, as-executed, and as-inspected viewpoints. An experiment was conducted to test selected open data standards' ability to integrate the lifecycle stages of engineering design, manufacturing, and quality assurance through a thorough implementation of a small scale model-based enterprise. The research team set out to answer: from design, through production, and final inspections, what are the hurdles that a manufacturer would face during the development of a fully linked and integrated information chain? The research team was not able to fully link all the required information, but value for industry was still identified. This paper presents the results of the experiment, provides guidance on how to overcome or mitigate identified challenges, and discusses the benefits or incentives to be gained from tracing or linking information through multiple stages a product lifecycle.

Effect of boron supplementation on laying performance of White Leghorn hens fed diet with and without adequate level of calcium.

This study was conducted in White Leghorn layers to ascertain the effect of boron (B) supplementation to calcium (Ca) inadequate diet under standard managemental practices. A total of 80 commercial White Leghorn hens, 25 weeks old with a uniform body weight, were randomly assigned to one of the 4 groups of 20 hens/replicates in each dietary group viz., normal calcium (NC)/Ca adequate, low calcium (LC)/Ca-inadequate, normal calcium with 40 ppm B (NCB) and low calcium with 40 ppm B (LCB). Dietary level of Ca was maintained at two levels, 100 (normal) and 90% (inadequate) of the requirement. Supplementation of B at 40 ppm improved (P < 0.01) egg production of layers from third month of trial as compared to un-supplemented group. Feed conversion ratio of layers was positively (P < 0.05) influenced by B supplementation in Ca-inadequate diet. Egg shell thickness of layers was found to be higher (P < 0.001) in groups supplemented 40 ppm B, irrespective of the level of Ca in the diets. Cracked egg production was also significantly (P < 0.01) lower in B-supplemented groups compared to Ca-inadequate group. Boron supplementation improved Ca retention irrespective of dietary Ca level. Low-Ca diet without boron supplementation resulted in lower retention (P < 0.05) of magnesium and boron. It is concluded that supplementation of 40 ppm B to Ca-inadequate diet ameliorated the lower laying performance in layers and confirms the usefulness of B in such abiotic stress situations.

Serotype and genotype diversity of dengue viruses circulating in India: a multi-centre retrospective study involving the Virus Research Diagnostic Laboratory Network in 2018.

OBJECTIVES: A retrospective study was undertaken to investigate the circulating dengue virus (DENV) serotypes and genotypes in India in 2018. METHODS: In total, 4963 samples referred to virus research diagnostic laboratories (n=21), the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV) and ICMR-NIV field units (n=2) for diagnosis of dengue in 2018 were tested using a real-time reverse transcription polymerase chain reaction assay for the presence of DENV serotypes. Representative samples were sequenced for the envelope (E) gene. RESULTS: Regional diversity was observed with regard to the dominant circulating serotypes. DENV-2 was found to be the most common serotype in many states. Thrombocytopenia, petechiae and malaise were associated with DENV-2 infection. Phylogenetic analyses of DENV E gene sequences revealed the circulation of genotypes I and V of DENV-1, two lineages of DENV-2 genotype IV, DENV-3 genotype III and DENV-4 genotype I. CONCLUSIONS: This study found regional differences in the prevalence of circulating DENV serotypes in India, and provides baseline data for continuous molecular surveillance. Molecular surveillance may have implications for predicting large-scale outbreaks of dengue if regional shifts in the predominantly circulating serotypes and genotypes are detected during the early phase of the dengue season.

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.

Parapsilorhynchus alluriensis, a new species of cyprinid fish (Teleostei: Cyprinidae) from the Eastern Ghats, of India.

A new species of cyprinid fish, Parapsilorhynchus alluriensis, is described from the Alluri Hills of Andhra Pradesh State, India. It is distinguished from its congeners by the combination of the following characters: A poorly-developed callous pad present behind lower lip; head deep (depth at occiput 47.3-72.3% head length, HL); body stout and deep (depth at dorsal fin origin 17.3-21.7 % standard length, SL); gape width 27.3-32.8% HL; inter-orbital space 33.9-43.2% HL; lower lip rounded; mouth opening situated very close to the anterior tip of snout; upper lip concealed by a poorly-developed rostral fold which is slightly fringed; minute papillae on rostral fold; 3 simple pectoral-fin rays; 33-34 lateral-line scales. A partial phylogeny based on the DNA Barcode COI gene suggests a sister-group relationship between the new species and P. prateri. Till date, the genus consists of four species from the Western Ghats, three from the Eastern Ghats, including the species described herein totaling it to seven from the peninsular India.

Effect of Zinc Nanoparticles on Milk Yield, Milk Composition and Somatic Cell Count in Early-Lactating Barbari Does.

Nano minerals have better bioavailability, efficient utilization, smaller dose rate, and stable interactions within the biological system. Efficacy of dietary supplementation of nano zinc particles on milk yield, milk composition, and somatic cell count was studied in periparturient Barbari does. Twenty-four Barbari goats (mean body weight 35 ± 1.5 kg) of about 4 months of pregnancy were divided into four groups (Gr I, Gr II, Gr III, and Gr IV) of six animals each. All the does were fed a common basal diet (containing 38.96 mg Zn/kg DM) of concentrate pellet and Bengal gram (Cicer arietinum) straw. No zinc was supplemented in does of Gr I (control group), while Gr II, Gr III, and Gr IV does were supplemented with 20 ppm inorganic zinc oxide, 10 ppm of nano zinc, and 20 ppm of nano zinc respectively. The experimental feeding was done for 75 days (30 days before kidding to 45 days after kidding). Results showed that yield and composition of milk in different groups of lactating does were not significantly (P < 0.05) affected by zinc supplementation. The percentages of solid-nonfat, fat, protein, lactose, and total solid were comparable (P > 0.05) among different groups of lactating does. The milk mineral levels of Zn, Cu, Na, Ca, and K were statistically similar (P > 0.05) in all the groups of goats. There was significantly (P < 0.05) lower somatic cell count (SCC) in zinc-supplemented groups (Gr II, Gr III, and Gr IV) as compared with the control (Gr I) group of does. SCC was lowest in Gr IV followed by Gr III, Gr II, and Gr I. The present study concluded that supplementation of inorganic zinc @ 20 ppm and nano zinc @ 10 and 20 ppm had no significant effect on milk yield/composition but reduced milk somatic cell count. The efficacy of nano zinc was found to be better as compared with normal inorganic form.

Defying gravity: Drops that climb up a vertical wall of their own accord.

Drops that move uphill on a gradient surface have been introduced in the past. In this paper, however, we present drops that climb a surface that does not have a gradient to begin with. In our study, Octadecylamine in Tetradecane (ODA/TD) drops were placed on either vertical or horizontal mica surfaces, and both the cases show spreading and retraction that initiate the motion of the ODA/TD drops. On horizontal surfaces, initially, the drop spreads in all directions. Then, after some time, which is a function of the solute concentration, the rear edge of the drop jerks in the direction opposite to spreading with a retraction that reminds breaststroke swimming motion: the front sides keep spreading while the back retracts, followed by the sides closing on themselves and pushing all the liquid forward which is the only place that never retracts. The front side of the drop then spreads faster in a way that reminds the circle that the arms make during breaststroke. The back and front sides of the drop continue to shrink and expand, respectively, with a net result of moving forward. The reason this motion can happen, is that the drop self-creates a local interfacial gradient at its surrounding. The direction of this self-induced interfacial gradient is against the gravity for inclined surfaces and is random if the surface is horizontal. Tilting the surface results in a local gradient that is preferentially opposite to the direction of gravity, hence the drop's motion results in climbing up. The drop leaves behind it a surfactant covered, but otherwise dry, surface. To the best of our knowledge such a system has not been explored before.

Drops That Change Their Mind: Spontaneous Reversal from Spreading to Retraction.

A liquid drop may spread faster on surfaces when surfactants are added. Here we show that after some time the spreading in such systems can, under certain conditions, spontaneously reverse to retraction and the droplet pulls itself back, receding from areas it has just recently wetted, elevating its center of mass in a jerklike motion. The duration from drop placement to the onset of retraction ranges from hours to less than a second primarily as a function of surfactant concentration. When the retraction is asymmetric, it results in drop motion, and when it is symmetric, the mass of the drop collects itself on its spot. This phenomenon, which was predicted theoretically in 2014, is apparently a general one for drops with surfactants; however, other factors, such as evaporation and contamination, prevented its observance so far.

Urinary Albumin Excretion, Estimated Glomerular Filtration Rate, and Prevalence of Microalbuminuria in Obese Nondiabetic and Nonhypertensive Adults: A Cross-Sectional Study.

CONTEXT: Obesity even in absence of diabetes and hypertension increases the risk for microalbuminuria (MAU), glomerular hyperfiltration, and therefore nephropathy. AIMS: This study aims to assess the urinary albumin excretion (UAE), prevalence of MAU, and values of estimated glomerular filtration rate (eGFR) in obese nondiabetic and nonhypertensive patients, vis a vis thin healthy subjects, and attempts to correlate anthropometric measurements with UAE and eGFR. SETTING AND DESIGN: Cross-sectional analytical study on 60 cases who were obese according to Asia Pacific guidelines and 60 nonobese controls. Patients with diabetes, hypertension, ischemic heart disease, and established renal disease were excluded. METHODS AND MATERIAL: Albuminuria was assessed in each patient by quantitative immunoturbidimetry method on a spot urine sample. eGFR was calculated by Cockcroft-Gault formula. STATISTICAL ANALYSIS: Data was analyzed using SPSS (2015 version). Mann-Whitney U-test, Fisher Exact test, and Spearman's correlation coefficient was used for various variables. RESULTS: The mean age of cases was 31.90 ± 6.32 years. About 78.33% were in class 1 and 21.66% in class 2 obese groups. The mean UAE at 21.20 ± 26.82 mg/g creatinine was higher in the case group. The prevalence of MAU was 11.66% and 3.33% in case and control groups, respectively. The cases had a significantly higher mean eGFR of 123.29 ± 20.49 mL/min/kg as compared with controls who had a mean eGFR of 106.59 ± 10.15 mL/min/kg. There was moderate correlation between anthropometric measurements and eGFR. CONCLUSION: Younger, class 1 obese patients had a higher UAE, eGFR, and three times higher MAU prevalence, even in absence of diabetes and hypertension, with a correlation between anthropometry and eGFR as compared with nonobese individuals.

Effect of clap-and-fling mechanism on force generation in flapping wing micro aerial vehicles.

The clap-and-fling effect, first observed in a number of insects, serves as a lift-enhancing mechanism for bio-inspired flapping wing micro aerial vehicles (MAV). In our comprehensive literature survey, we observe that the effect manifests differently in insects and contemporary MAVs; insects have active control over the angle of attack and stroke plane of the wing, whereas a number of kinematic parameters of an MAV's flexible wings are determined passively. Although there is consensus that flinging motion significantly enhances aerodynamic lift, the effect of clapping motion is not well-studied. To address this gap, we experimentally quantify the contribution of clapping motion using force measurement and particle image velocimetry. No significant enhancement in lift was observed due to clapping motion, because the momentum jet was too weak. However, the kinematics and flow conditions in our study were notably different from those in the previous studies on insect models. The wings of the MAV are flexible, and deform passively. Hence, the clapping of the trailing edges, and the appearance of a trailing edge momentum jet, was delayed and significantly suppressed. Using force measurement and CFD simulations, it was also found that the lesser the distance between the leading edges of the wings at the end of clap, the higher is the lift due to the subsequent fling.

Study of structural and magnetic properties and heat induction of gadolinium-substituted manganese zinc ferrite nanoparticles for in vitro magnetic fluid hyperthermia.

This article outlines the synthesis of gadolinium (Gd)-doped manganese zinc ferrite magnetic nanoparticles (MNPs) as potential magnetic carriers for magnetic fluid hyperthermia (MFH). MNPs with high specific loss power (SLP; 146 W/g) have been developed and used for an in vitro hyperthermia study. The treatment of MFH is fruitful if there is an adequate number of MNPs in tumor cells with the highest SLP to rapidly generate heat while minimizing thermal injury to surrounding healthy tissue. X-ray diffraction patterns of the studied particles confirm the formation of a cubic spinel structure. Field emission scanning electron micrographs showed homogeneous distributions of particles with some agglomerates with a granular appearance. Transmission electron microscopy analysis showed the presence of agglomerated spherical particles at the surface. The substitution of Gd resulted in superparamagnetism at room temperature as confirmed by vibrating sample magnetometer analysis. The estimated saturation magnetization reduced from 48.6 to 28.2 emu/g with an increase in Gd concentration. However, the coercivity increased from 1093 Oe to 1597 Oe. Field cooled and zero field cooled measurements showed Curie temperatures from 315 to 326 K, as required for MFH applications. Cell viability measurements indicated that the MNPs are nontoxic to A549 cells for the studied concentrations of particle fraction and a contact time of up to 24 h. The interaction of the MNPs with A549 cells was highlighted from an image captured by an inverted microscope. In order to treat cancer in vivo, an in vitro hyperthermia study has initially been carried out with A549 cells.

Iron catalysis of lipid peroxidation in ferroptosis: Regulated enzymatic or random free radical reaction?

Duality of iron as an essential cofactor of many enzymatic metabolic processes and as a catalyst of poorly controlled redox-cycling reactions defines its possible biological beneficial and hazardous role in the body. In this review, we discuss these two "faces" of iron in a newly conceptualized program of regulated cell death, ferroptosis. Ferroptosis is a genetically programmed iron-dependent form of regulated cell death driven by enhanced lipid peroxidation and insufficient capacity of thiol-dependent mechanisms (glutathione peroxidase 4, GPX4) to eliminate hydroperoxy-lipids. We present arguments favoring the enzymatic mechanisms of ferroptotically engaged non-heme iron of 15-lipoxygenases (15-LOX) in complexes with phosphatidylethanolamine binding protein 1 (PEBP1) as a catalyst of highly selective and specific oxidation reactions of arachidonoyl- (AA) and adrenoyl-phosphatidylethanolamines (PE). We discuss possible role of iron chaperons as control mechanisms for guided iron delivery directly to their "protein clients" thus limiting non-enzymatic redox-cycling reactions. We also consider opportunities of loosely-bound iron to contribute to the production of pro-ferroptotic lipid oxidation products. Finally, we propose a two-stage iron-dependent mechanism for iron in ferroptosis by combining its catalytic role in the 15-LOX-driven production of 15-hydroperoxy-AA-PE (HOO-AA-PE) as well as possible involvement of loosely-bound iron in oxidative cleavage of HOO-AA-PE to oxidatively truncated electrophiles capable of attacking nucleophilic targets in yet to be identified proteins leading to cell demise.