MRI Radiomics in Imaging of Focal Hepatic Lesions: A Narrative Review.

Magnetic resonance imaging (MRI) is generally used to identify, describe, and evaluate treatment responses for focal hepatic lesions. However, the diagnosis and differentiation of such lesions require considerable input from radiologists. In order to reduce these difficulties, radiomics is an artificial intelligence (AI)-based quantitative method that employs the extraction of image features to reliably detect and differentiate focal hepatic lesions. MRI radiomics is a novel technique for the characterization of focal hepatic lesions. It can aid in preoperative evaluation, treatment approach, and forecast microvascular invasion. Although many studies have illustrated its efficiency there are certain limitations such as the absence of a large diverse dataset, comparison with other AI models, integration with histopathological findings, clinical utility, and feasibility.

Comparative Study of Levels of Serum Bilirubin, Serum Transaminase, Serum Alkaline Phosphatase, and Prothrombin Time After Laparoscopic Cholecystectomy and Open Cholecystectomy.

Laparoscopic cholecystectomy (LC) is universally accepted as the gold standard treatment for symptomatic gallstones. However, it has some drawbacks. Some of the major drawbacks of LC include increased bile duct injuries and longer operation time. Furthermore, it may cause changes in the body systems, such as alterations in acid-base, pulmonary status, cardiovascular system, and liver function. Thus far, no causes for these changes have been identified. This study aimed to evaluate the effect of laparoscopic and open cholecystectomy on liver enzymes, prothrombin time (PT), and serum bilirubin. In the current study, we found significant increases in aspartate transferase (AST), alanine transaminase (ALT), and total bilirubin, on day 1 and day 3 after LC but no significant change in alkaline phosphatase (ALKP) and PT. It is important for surgeons to know about these transient changes in the immediate postoperative period to avoid misdiagnosis and adopt proper treatment and management.

Nanoremediation strategies to address environmental problems.

A rapid rise in population, extensive anthropogenic activities including agricultural practices, up-scaled industrialization, massive deforestation, etc. are the leading causes of environmental degradation. Such uncontrolled and unabated practices have affected the quality of environment (water, soil, and air) synergistically by accumulating huge quantities of organic and inorganic pollutants in it. Environmental contamination is posing a threat to the existing life on the Earth, therefore, demands the development of sustainable environmental remediation approaches. The conventional physiochemical remediation approaches are laborious, expensive, and time-consuming. In this regard, nanoremediation has emerged as an innovative, rapid, economical, sustainable, and reliable approach to remediate various environmental pollutants and minimize or attenuate the risks associated with them. Owing to their unique properties such as high surface area to volume ratio, enhanced reactivity, tunable physical parameters, versatility, etc. nanoscale objects have gained attention in environmental clean-up practices. The current review highlights the role of nanoscale objects in the remediation of environmental contaminants to minimize their impact on human, plant, and animal health; and air, water, and soil quality. The aim of the review is to provide information about the applications of nanoscale objects in dye degradation, wastewater management, heavy metal and crude oil remediation, and mitigation of gaseous pollutants including greenhouse gases.

Anticoagulant mechanism, pharmacological activity, and assessment of preclinical safety of a novel fibrin(ogen)olytic serine protease from leaves of Leucas indica.

The harnessing of medicinal plants containing a plethora of bioactive molecules may lead to the discovery of novel, potent and safe therapeutic agents to treat thrombosis-associated cardiovascular diseases. A 35 kDa (m/z 34747.5230) serine protease (lunathrombase) showing fibrin(ogen)olytic activity and devoid of N- and O- linked oligosaccharides was purified from an extract of aqueous leaves from L. indica. The LC-MS/MS analysis, de novo sequencing, secondary structure, and amino acid composition determination suggested the enzyme's novel characteristic. Lunathrombase is an αß-fibrinogenase, demonstrating anticoagulant activity with its dual inhibition of thrombin and FXa by a non-enzymatic mechanism. Spectrofluorometric and isothermal calorimetric analyses revealed the binding of lunathrombase to fibrinogen, thrombin, and/or FXa with the generation of endothermic heat. It inhibited collagen/ADP/arachidonic acid-induced mammalian platelet aggregation, and demonstrated antiplatelet activity via COX-1 inhibition and the upregulation of the cAMP level. Lunathrombase showed in vitro thrombolytic activity and was not inhibited by endogenous protease inhibitors α2 macroglobulin and antiplasmin. Lunathrombase was non-cytotoxic to mammalian cells, non-hemolytic, and demonstrated dose-dependent (0.125-0.5 mg/kg) in vivo anticoagulant and plasma defibrinogenation activities in a rodent model. Lunathrombase (10 mg/kg) did not show toxicity or adverse pharmacological effects in treated animals.

Peptide Solubility Limits: Backbone and Side-Chain Interactions.

We calculate the solubility limit of pentapeptides in water by simulating the phase separation in an oversaturated aqueous solution. The solubility limit order followed by our model peptides (GGRGG > GGDGG > GGGGG > GGVGG > GGQGG > GGNGG > GGFGG) is found to be the same as that reported for amino acid monomers from experiment (R > D > G > V > Q > N > F). Investigation of dynamical properties of peptides shows that the higher the solubility of a peptide is, the lower the time spent by the peptide in the aggregated cluster is. We also demonstrate that fluctuations in conformation and hydration number of peptide in monomeric form are correlated with the solubility of the peptide. We considered energetic mechanisms and dynamical properties of interbackbone CO-CO and CO···HN interactions. Our results confirm that CO-CO interactions more than the interbackbone H-bonds are important in peptide self-assembly and association. Further, we find that the stability of H-bonded peptide pairs arises mainly from coexisting CO-CO and CO···HN interactions.

Antioxidant Effect of Sericin in Brain and Peripheral Tissues of Oxidative Stress Induced Hypercholesterolemic Rats.

This study evaluated the antioxidant effect of crude sericin extract (CSE) from Antheraea assamensis in high cholesterol fed rats. Investigation was conducted by administering graded oral dose of 0.25 and 0.5 gm/kg body weight (b.w.)/day of CSE for a period of 28 days. Experiments were conducted in 30 rats and were divided into five groups: normal control, high cholesterol fed (HCF), HCF + 0.065 gm/kg b.w./day fenofibrate (FF), HCF + sericin 0.25 gm/kg b.w./day (LSD), and HCF + sericin 0.5 gm/kg b.w./day (HSD). In brain, heart, liver, serum, and kidney homogenates nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), superoxide dismutase, reduced glutathione (GSH) was measured. LSD treatment prevented the alterations in GSH and PCC levels in hypercholesterolemic (HyC) brain tissue homogenates of rats. CSE lowers the serum total cholesterol level in HyC rats by promoting fecal cholesterol (FC) excretion. CSE increases FC level by promoting inhibition of cholesterol absorption in intestine. The endogenous antioxidant reduced significantly and the oxidative stress marker TBARS level increases significantly in the peripheral tissue of HCF rats. However, the administration of LSD and HSD exhibited a good antioxidant activity by reducing the TBARS level and increasing the endogenous antioxidant in peripheral tissue. In addition, a histological examination revealed loss of normal liver and kidney architecture in cholesterol fed rats which were retained in sericin treated groups. The findings of this study suggested that CSE improves hypercholesterolemia in rats fed a HyC diet. Clinical relevance of this effect of CSE seems worthy of further studies.

Polyphenol Rich Extract of Garcinia pedunculata Fruit Attenuates the Hyperlipidemia Induced by High Fat Diet.

Fatty foods, the most common diet today are the crux of many metabolic disorders which need urgent attention. Garcinia pedunculata Roxb. (GP, Clusiaceae) is a plant found available in Northeast (NE) region of India, is considered to have versatile therapeutic properties. The people of this region has been using dried pulp of GP fruit for the treatment of different stomach related diseases traditionally. This study aimed at evaluating the potential therapeutic action of the polyphenol-rich methanolic extract of the fruit in experimental induced obese rats. In vitro antioxidant and antidiabetic activity of GP extracts, i.e., fruit extract (GF) and seed extract (GS) were determined by using various methods viz., 1,1-diphenyl-2 picrylhydrazyl (DPPH), 2,2'-Azinobis (3-ethyl benzthiazoline-6-sulphonic acid) (ABTS(•+)), nitroblue tetrazolium (NBT) and α-glucosidase inhibition assay for detection of antihyperglycemic activity. In vivo antilipidemic and antiobesity activities were evaluated by administrating oral dose of GF for 60 days on a high-fat diet (HFD) induced hyperlipidemia in the rat. GF showed higher antioxidant activity than GS by DPPH radical scavenging (IC50 = 4.01 µg/ml), ABTS(•+) (IC50 = 0.82 µg/ml), NBT (IC50 = 0.07 µg/ml) and also showed notable α-glucosidase inhibitory activity (IC50 = 19.26 µg/ml). Furthermore, GF treated rat revealed a reduction in the body weight (~60%), serum total cholesterol (33%), triglycerides (32%), low-density lipoprotein (38%) and liver biomarker enzymes after 60 days HFD fed animals. Simultaneously, GF supplementation significantly protected the HFD induced changes in hematological parameters. Histological observations clearly differentiate the structural changes in liver of HFD and GF treated group. This novel dietary lipid adsorbing agent of GF exhibited prevention of hyperlipidemia induced by HFD in the rat.

Antidiabetic and Antilipidemic Effect of Musa balbisiana Root Extract: A Potent Agent for Glucose Homeostasis in Streptozotocin-Induced Diabetic Rat.

Folklore studies have revealed that Musa balbisiana Colla (MB; Family: Musaceae) has high medicinal properties. The purpose of the present study is to evaluate antihyperglycemic, and antioxidant activity of MB extracts in streptozotocin (STZ) induced diabetic rats. In vitro antioxidant and antidiabetic activity of MB extracts, i.e., root extract (RE), shoot extract and inflorescence extract were determined by using various methods viz 1,-1-diphenyl-2-picrylhydrazyl (DPPH) and a method to assess their possible effect on glucose diffusion across gastrointestinal tract and identify bioactive compound of potent extract. In vivo antilipidemic and antidiabetic activity was evaluated by administrating oral dose of RE for 15 days on STZ- induced diabetic rat. RE showed highest antioxidant activity by scavenging DPPH radical (IC50 32.96 µg/ml) and inhibit 30% glucose movement in vitro. The methanol extract of root showed the presence of calyx [4] arene category of the compound. Furthermore, RE treated rat revealed a reduction in fasting blood glucose (62.5%), serum total cholesterol (36.2%), triglyceride (54.5%), and low-density lipoprotein (50.94%) after 15 days as compared to STZ treated animal. There was an initiation of regenerative structures of the affected organs after 15 days of RE treatment. Histopathological observations clearly differentiate the structural changes in pancreas, liver, and kidney of STZ and RE treated group. The presence of calyx [4] arene class of compound may be responsible for its antioxidant and antidiabetic properties by absorbing glucose in vivo.

Interactions of S-peptide analogue in aqueous urea and trimethylamine-N-oxide solutions: a molecular dynamics simulation study.

The ability of the osmolyte, trimethylamine-N-oxide (TMAO), to protect proteins from deleterious effect of urea, another commonly available osmolyte, is well-established. However, the molecular mechanism of this counteraction is not understood yet. To provide a molecular level understanding of how TMAO protects proteins in highly concentrated urea solution, we report here molecular dynamics simulation results of a 15-residue model peptide in two different conformations: helix and extended. For both conformations, simulations are carried out in pure water as well as in binary and ternary aqueous solutions of urea and TMAO. Analysis of solvation characteristics reveals direct interactions of urea and TMAO with peptide residues. However, the number of TMAO molecules that enter in the first solvation shell of the peptide is significantly lower than that of urea, and, unlike water and urea, TMAO shows its inability to form hydrogen bond with backbone oxygen and negatively charged sidechains. Preferential accumulation of urea near the peptide surface and preferential exclusion of TMAO from the peptide surface are observed. Inclusion of osmolytes in the peptide solvation shell leads to dehydration of the peptide in binary and ternary solutions of urea and TMAO. Solvation of peptide residues are investigated more closely by calculating the number of hydrogen bonds between the peptide and solution species. It is found that number of hydrogen bonds formed by the peptide with solution species increases in binary urea solution (relative to pure water) and this relative enhancement in hydrogen bond number reduces upon addition of TMAO. Our simulation results also suggest that, in the ternary solution, the peptide solvation layer is better mixed in terms of water and urea as compared to binary urea solution. Implications of the results for counteraction mechanism of TMAO are discussed.

Trimethylamine-N-oxide's effect on polypeptide solvation at high pressure: a molecular dynamics simulation study.

The solvation characteristics of a 15-residue polypeptide and also the structure of the solution in the presence and absence of trimethylamine-N-oxide (TMAO), one of the strongest known protein stabilizers among the natural osmolytes both at low and high pressures, are investigated under high pressure conditions by employing the molecular dynamics simulation technique. The goal is to provide a molecular level understanding of how TMAO protects proteins at elevated pressures. Two different conformations of the polypeptide are used: helix and extended. Analysis of peptide hydration characteristics reveals that the pressure-induced enhancement of hydration number is higher for the extended state as compared to the helix. TMAO shows an opposite effect and causes more dehydration of the extended state. The total number of atomic sites that solvate peptide residues increases in the presence of TMAO, whereas the number of hydrogen bonds formed by peptide with solution species reduces due to the inability of TMAO to donate its hydrogen to peptide hydrogen bonding sites. In solution, both hydrophobic and hydrogen bonding sites of TMAO are found to be well solvated by water molecules and solvation of TMAO enhances water structure and reduces the number of nearest identical neighbors for water. Pressure and TMAO are seen to have counteracting effects on water structural properties. Implications of these results for counteracting mechanism of TMAO are discussed.

Exploring the molecular mechanism of trimethylamine-N-oxide's ability to counteract the protein denaturing effects of urea.

Protein denaturation in highly concentrated urea solution is a well-known phenomenon. The counteracting effect of a naturally occurring osmolyte, trimethylamine-N-oxide (TMAO), against urea-conferred protein denaturation is also well-established. However, what is largely unknown is the mechanism by which TMAO counteracts this denaturation. To provide a molecular level understanding of how TMAO protects proteins in highly concentrated urea solution, we report here the structural, energetic, and dynamical properties of N-methylacetamide (NMA) solutions that also contain urea and/or TMAO. The solute NMA is of interest mainly because it contains the peptide linkage in addition to hydrophobic sites and represents the typical solvent-exposed state of proteins. Molecular dynamics computer simulation technique is employed in this study. Analysis of solvation characteristics reveals dehydration of NMA and reduction in hydrogen bond number between NMA oxygen and water upon addition of TMAO. The effect of TMAO on NMA-urea interaction is found to be insignificant. Because TMAO cannot donate its hydrogen to NMA oxygen, the total number of hydrogen bonds formed by NMA oxygen with solution species decreases in the presence of TMAO. In solution, TMAO is found to interact strongly with water and urea. Solvation of TMAO makes the water hydrogen bonding network relatively stronger and reduces relaxation of urea-water hydrogen bonds. Implications of these results for counteracting mechanism of TMAO are discussed.

Crucial importance of water structure modification on trimethylamine N-oxide counteracting effect at high pressure.

Penetration of water molecules into the protein interior under high hydrostatic pressure conditions, leading to protein structural transition, is a well-known phenomenon. The counteracting effect of a naturally occurring osmolyte, trimethylamine N-oxide (TMAO), against pressure-induced protein denaturation is also well-established. But, what is largely unknown is the mechanism by which TMAO counteracts this protein denaturation. So to provide a molecular level understanding of how TMAO protects proteins at high pressure, we report here molecular dynamics (MD) computer simulation results for aqueous solutions of N-methylacetamide (NMA) with different TMAO concentrations over a wide range of pressures relevant to protein denaturation. Hydration behavior of NMA is analyzed at different conditions chosen. It is observed that hydrostatic pressure leads to a significant compression of hydration shell of nonpolar groups and increases hydration number. The compression is relatively insignificant in the vicinity of hydrogen bonding sites. TMAO can prevent pressure-induced enhanced hydration of NMA molecules. Interaction of TMAO with NMA and the structural and dynamical properties of water (site-site radial distribution function, coordination number, hydrogen-bond number, and lifetime) are also investigated to find the origin of the counteracting action of TMAO. Our results confirm that TMAO and pressure have counteracting effects on the water structural and dynamical properties, giving an explanation as to how TMAO counteracts pressure-conferred denaturation of proteins.

The effect of aqueous solutions of trimethylamine-N-oxide on pressure induced modifications of hydrophobic interactions.

To understand the mechanism of protein protection by the osmolyte trimethylamine-N-oxide (TMAO) at high pressure, using molecular dynamics (MD) simulations, solvation of hydrophobic group is probed in aqueous solutions of TMAO over a wide range of pressures relevant to protein denaturation. The hydrophobic solute considered in this study is neopentane which is a considerably large molecule. The concentrations of TMAO range from 0 to 4 M and for each TMAO concentration, simulations are performed at five different pressures ranging from 1 atm to 8000 atm. Potentials of mean force are calculated and the relative stability of solvent-separated state over the associated state of hydrophobic solute are estimated. Results suggest that high pressure reduces association of hydrophobic solutes. From computations of site-site radial distribution function followed by analysis of coordination number, it is found that water molecules are tightly packed around the nonpolar particle at high pressure and the hydration number increases with increasing pressure. On the other hand, neopentane interacts preferentially with TMAO over water and although hydration of neopentane reduces in presence of this osmolyte, TMAO does not show any tendency to prevent the pressure-induced dispersion of neopentane moieties. It is also observed that TMAO molecules prefer a side-on orientation near the neopentane surface, allowing its oxygen atom to form favorable hydrogen bonds with water while maintaining some hydrophobic contacts with neopentane. Analysis of hydrogen-bond properties and solvation characteristics of TMAO reveals that TMAO can form hydrogen bonds with water and it reduces the identical nearest neighbor water molecules caused by high hydrostatic pressures. Moreover, TMAO enhances life-time of water-water hydrogen bonds and makes these hydrogen bonds more attractive. Implication of these results for counteracting effect of TMAO against protein denaturation at high pressures are discussed.

Effect of trimethylamine-N-oxide on pressure-induced dissolution of hydrophobic solute.

Molecular dynamics simulations are performed to study the effects of increasing trimethylamine-N-oxide (TMAO) concentration on the pressure-induced dissolution of hydrophobic solutes immersed in water. Such systems are of interest mainly because pressure increases the dissolution of hydrophobic protein interior causing protein denaturation and TMAO acts to offset the protein denaturing effect of high hydrostatic pressures. In view of this, in this study, methane molecules are considered as model hydrophobic molecules and simulations are performed for four independent TMAO solutions each at four different pressures ranging from 2 to 8 kbar. From potentials of mean force calculations, it is found that application of pressure reduces the free energy difference between contact minimum (CM) and solvent-separated (SSM) minimum of hydrophobic solute, suggesting dissolution at high pressures. TMAO, on the other hand, increases the relative stability of CM state of methane molecules relative to its SSM state. High packing efficiency of water molecules around the hydrophobic solute at high pressure is observed. Also observed are TMAO-induced enhancement of water structure and direct hydrogen-bonding interaction between TMAO and water and the correlated dehydration of hydrophobic solute. From hydrogen bond properties and dynamics calculations, it is observed that pressure increases average number of water-water hydrogen bonds while reduces their life-times. In contrast, TMAO reduces water-water hydrogen bonding but enhances their life-times. These results suggest that TMAO can reduce water penetration into the protein interior by enhancing water structure and also forming hydrogen bonds with water and hence counteracts protein unfolding.

The effect of pressure on the hydration structure around hydrophobic solute: a molecular dynamics simulation study.

Molecular dynamics simulations are performed to study the effects of pressure on the hydrophobic interactions between neopentane molecules immersed in water. Simulations are carried out for five different pressure values ranging from 1 atm to 8000 atm. From potential of mean force calculations, we find that with enhancement of pressure, there is decrease in the well depth of contact minimum (CM) and the relative stability of solvent separated minimum over CM increases. Lower clustering of neopentane at high pressure is also observed in association constant and cluster-structure analysis. Selected site-site radial distribution functions suggest efficient packing of water molecules around neopentane molecules at elevated pressure. The orientational profile calculations of water molecules show that the orientation of water molecules in the vicinity of solute molecule is anisotropic and this distribution becomes flatter as we move away from the solute. Increasing pressure slightly changes the water distribution. Our hydrogen bond properties and dynamics calculations reveal pressure-induced formation of more and more number of water molecules with five and four hydrogen bond at the expense of breaking of two and three hydrogen bonded water molecules. We also find lowering of water-water continuous hydrogen bond lifetime on application of pressure. Implication of these results for relative dispersion of hydrophobic molecules at high pressure are discussed.

Association of small hydrophobic solute in presence of the osmolytes urea and trimethylamine-N-oxide.

Influences of two naturally occurring osmolytes, urea and trimethylamine-N-oxide (TMAO), on hydrophobic interactions of methane are investigated by performing molecular dynamics (MD) simulations. In this study, we have used two different models of methane: one is of single united site (UA), and the other contains 5-sites (AA). We observe that two methane models behave similarly in pure water and in aqueous osmolyte solutions except for the fact that AA model of methane behaves slight differently in aqueous binary urea solution. Our potentials of mean force (PMF) calculations followed by association constant estimation and cluster structure analyses suggest urea-induced enhancement of methane association for the methane AA model. For both models, we observe the dehydration of methane molecules in presence of osmolytes. We also find the collapse of the second shell of water by urea and water structure enhancement by TMAO molecules. Our preferential interaction parameter calculations show that in binary aqueous urea solution methane molecules are expelled by urea molecules and this effect is more pronounced for the AA model. On the other hand, in binary aqueous TMAO solution, methane prefers to interact more with TMAO than water. Our water orientational structure calculations show that the orientation of water molecules near to hydrophobic moiety is anisotropic and osmolytes have a negligible effect on it. We also observe the osmolyte-induced water-water hydrogen bond lifetime increase in the hydration shell of methane as well as in the subsequent layers.

Hydrophobic interactions in presence of osmolytes urea and trimethylamine-N-oxide.

Molecular dynamics simulations were carried out to study the influences of two naturally occurring osmolytes, urea, and trimethylamine-N-oxide (TMAO) on the hydrophobic interactions between neopentane molecules. In this study, we used two different models of neopentane: One is of single united site (UA) and another contains five-sites. We observe that, these two neopentane models behave differently in pure water as well as solutions containing osmolytes. Presence of urea molecules increases the stability of solvent-separated state for five-site model, whereas osmolytes have negligible effect in regard to clustering of UA model of neopentane. For both models, dehydration of neopentane and preferential solvation of it by urea and TMAO over water molecules are also observed. We also find the collapse of the second-shell of water by urea and water structure enhancement by TMAO. The orientational distributions of water molecules around different layers of neopentane were also calculated and we find that orientation of water molecules near to hydrophobic moiety is anisotropic and osmolytes have negligible effect on it. We also observe osmolyte-induced water-water hydrogen bond life time increase in the hydration shell of neopentane as well as in the subsequent water layers.