Pharmacological potential of micheliolide: A focus on anti-inflammatory and anticancer activities.

Micheliolide (MCL) is a chief constituent of plants such as Magnolia grandiflora L., Michelia compressa (Maxim.) Sarg. and Michelia champaca L. It is known to exhibit significant anticancer activity by various scientific investigations. This review aims to emphasize the anticancer and antiinflammatory activities of MCL. In this review, we summarized the published data in peer-reviewed manuscripts published in English. Our search was based on the following scientific search engines and databases: Scopus, Google Scholar, ScienceDirect, Springer, PubMed, and SciFinder, MCL possesses a broad spectrum of medicinal properties like other sesquiterpene lactones. The anticancer activity of this compound may be attributed to the modulation of several signaling cascades (PI3K/Akt and NF-κB pathways). It also induces apoptosis by arresting the cell cycle at the G1/G0 phase, S phase, and G2/M phase in many cancer cell lines. Very little data is available on its modulatory action on other signaling cascades like MAPK, STAT3, Wnt, TGFß, Notch, EGFR, etc. This compound can be potentiated as a novel anticancer drug after thorough investigations in vitro, in vivo, and in silico-based studies.

Assessment of ubiquitin specific Peptidase-18 gene in peripheral blood of chronic hepatitis C patients treated with direct-acting antiviral drugs.

Hepatitis C virus (HCV) infection remains one of the leading causes of liver complications globally. Ubiquitin Specific Peptidase-18 (USP18) is a ubiquitin-specific protease that cleaves interferon-stimulated gene 15 (ISG15) from ISGylated protein complexes and is involved in regulating interferon responsiveness. To study the effect of direct-acting antivirals (DAAs) on the USP18 gene using qPCR, 132 participants were recruited and classified into different groups based on treatment duration. USP18 expression was raised compared to rapid virologic response (RVR) and early virologic response (EVR) groups with P = 0.0026 and P = 0.0016, respectively. USP18 was found to be 7.36 folds higher in naïve patients than those with RVR and sustained viral response (SVR). In RVR and SVR groups where patients had cleared HCV RNA after treatment with direct-acting antiviral agents (DAA) therapy, the expression of USP18 was found to be low, with a fold change of 1.3 and 1.4 folds, respectively. Expression of USP18 was significantly higher in the non-RVR group than in the RVR group. In the No EVR group, gene expression was significantly higher than in the EVR group. It is concluded that targeting HCV proteins using DAAs can cause USP18 expression to be normalized more effectively. Moreover, USP18 is a vital marker indicating treatment resistance and distinguishing responders from non-responders during DAA therapy.

Synthesis of new bis(dimethylamino)benzophenone hydrazone for diabetic management: In-vitro and in-silico approach.

Inhibiting α-glucosidase is a reliable method for reducing blood sugar levels in diabetic individuals. Bis(dimethylamino)benzophenone derivatives 1-27 were synthesized from bis(dimethylamino)benzophenone via two-step reaction. Different spectroscopic techniques, including EI-MS and 1H NMR, were employed to characterize all synthetic derivatives. The elemental composition of synthetic compounds was confirmed by elemental analysis and results were found in agreement with the calculated values. The synthetic compounds 1-27 were evaluated for α-glucosidase inhibitory activity, except five compounds all derivatives showed good to moderate inhibitory potential in the range of IC50 = 0.28 ± 2.65 - 0.94 ± 2.20 µM. Among them, the most active compounds were 5, 8, 9, and 12 with IC50 values of 0.29 ± 4.63, 0.29 ± 0.93, 0.28 ± 3.65, and 0.28 ± 2.65, respectively. Furthermore, all these compounds were found to be non-toxic on human fibroblast cell lines (BJ cell lines). Kinetics study of compounds 8 and 9 revealed competitive type of inhibition with Ki values 2.79 ± 0.011 and 3.64 ± 0.012 µM, respectively. The binding interactions of synthetic compounds were also confirmed through molecular docking studies that indicated that compounds fit well in the active site of enzyme. Furthermore, a total of 30ns MD simulation was carried out for the most potent complexes of the series. The molecular dynamics study revealed that compound-8 and compound-12 were stable during the MD simulation.

Serum metallomics reveals insights into the associations of elements with the progression of preleukemic diseases toward acute leukemia.

Acute leukemia (AL) is a critical neoplasm of white blood cells with two main subtypes: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This study is focused on understanding the association of the preleukemic disease aplastic anemia (APA) with ALL and AML at metallomic level, using healthy subjects as a control. In this study, a validated and efficient inductively coupled plasma-mass spectrometry/MS-based workflow was employed to profile a total of 13 metallomic features. The study encompassed 41 patients with AML, 62 patients with ALL, 46 patients with APA, and 55 age-matched healthy controls. The metallomic features consisted of eight essential elements (Ca, Co, Cu, Fe, Mg, Mn, Se, and Zn) and five non-essential/toxic elements (Ag, Cd, Cr, Ni, and Pb). Six out of the 13 elements were found to be substantially different (P < .05) using absolute concentrations between serum samples of AL (ALL and AML) and preleukemia (APA) patients in comparison with healthy subjects. Elements including magnesium, calcium, iron, copper, and zinc were upregulated and only one element (chromium) was downregulated in serum samples of disease when compared with healthy subjects. Through the utilization of both univariate tests and multivariate classification modeling, it was determined that chromium exhibited a progressive behavior among the studied elements. Specifically, chromium displayed a sequential upregulation from healthy individuals to preleukemic disease (APA), and ultimately in patients diagnosed with ALL. Overall, metallomic-based biomarkers may have the utility to predict the association of APA with ALL.

Age and sex differences in the association between neighborhood socioeconomic environment and incident diabetes: Results from the diabetes location, environmental attributes and disparities (LEAD) network.

Objective: Worse neighborhood socioeconomic environment (NSEE) may contribute to an increased risk of type 2 diabetes (T2D). We examined whether the relationship between NSEE and T2D differs by sex and age in three study populations. Research design and methods: We conducted a harmonized analysis using data from three independent longitudinal study samples in the US: 1) the Veteran Administration Diabetes Risk (VADR) cohort, 2) the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, and 3) a case-control study of Geisinger electronic health records in Pennsylvania. We measured NSEE with a z-score sum of six census tract indicators within strata of community type (higher density urban, lower density urban, suburban/small town, and rural). Community type-stratified models evaluated the likelihood of new diagnoses of T2D in each study sample using restricted cubic splines and quartiles of NSEE. Results: Across study samples, worse NSEE was associated with higher risk of T2D. We observed significant effect modification by sex and age, though evidence of effect modification varied by site and community type. Largely, stronger associations between worse NSEE and diabetes risk were found among women relative to men and among those less than age 45 in the VADR cohort. Similar modification by age group results were observed in the Geisinger sample in small town/suburban communities only and similar modification by sex was observed in REGARDS in lower density urban communities. Conclusions: The impact of NSEE on T2D risk may differ for males and females and by age group within different community types.

Chalcones: The flavonoid derivatives synthesis, characterization, their antioxidant and in vitro/in vivo antidiabetic potentials.

Chalcones (designated JA1, JA2 and JA3) were prepared from aromatic aldehyde and acetophenone which were then characterized using various spectroscopic techniques. The antioxidant potential of synthesized compounds was evaluated against DPPH free radical whereas the antidiabetic potential was determined against alpha glucosidase. Further the antidiabetic potential of the synthesized compounds was evaluated in rat model which were given orally experimental animals in doses 10 and 20 mg/kg body weight. The blood biochemical parameters like total cholesterol, triglycerides, alanine phosphatase, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, serum creatinine, HDL, and LDL levels were determined using commercially available kits. The antioxidant potential was found high for JA3 followed by JA2 with IC50 value of 64.02 ± 1.47 µg/ml whereas against alpha glucosidase again the same compound with IC50 of 63.04 µg/ml exhibited highest inhibitory potential. The blood glucose level was brought to almost normal level (126.88 and 119.13 mg/dl at 10 and 20 mg/kg body weight) in diabetic rats (induced by STZ) by compound JA3 at the tested doses in comparison to acarbose at day 28th. The blood biochemical parameters were normalized in diabetic rats by compound JA3 compared with diabetic control group. Based on the results JA3 should be considered as effective antioxidant and antidiabetic drug candidate.

Associations between PM2.5 and O3 exposures and new onset type 2 diabetes in regional and national samples in the United States.

BACKGROUND: Exposure to particulate matter ≤2.5 µm in diameter (PM2.5) and ozone (O3) has been linked to numerous harmful health outcomes. While epidemiologic evidence has suggested a positive association with type 2 diabetes (T2D), there is heterogeneity in findings. We evaluated exposures to PM2.5 and O3 across three large samples in the US using a harmonized approach for exposure assignment and covariate adjustment. METHODS: Data were obtained from the Veterans Administration Diabetes Risk (VADR) cohort (electronic health records [EHRs]), the Reasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort (primary data collection), and the Geisinger health system (EHRs), and reflect the years 2003-2016 (REGARDS) and 2008-2016 (VADR and Geisinger). New onset T2D was ascertained using EHR information on medication orders, laboratory results, and T2D diagnoses (VADR and Geisinger) or report of T2D medication or diagnosis and/or elevated blood glucose levels (REGARDS). Exposure was assigned using pollutant annual averages from the Downscaler model. Models stratified by community type (higher density urban, lower density urban, suburban/small town, or rural census tracts) evaluated likelihood of new onset T2D in each study sample in single- and two-pollutant models of PM2.5 and O3. RESULTS: In two pollutant models, associations of PM2.5, and new onset T2D were null in the REGARDS cohort except for in suburban/small town community types in models that also adjusted for NSEE, with an odds ratio (95% CI) of 1.51 (1.01, 2.25) per 5 µg/m3 of PM2.5. Results in the Geisinger sample were null. VADR sample results evidenced nonlinear associations for both pollutants; the shape of the association was dependent on community type. CONCLUSIONS: Associations between PM2.5, O3 and new onset T2D differed across three large study samples in the US. None of the results from any of the three study populations found strong and clear positive associations.

Triazolothiadiazoles and Triazolothiadiazines as New and Potent Urease Inhibitors: Insights from In Vitro Assay, Kinetics Data, and In Silico Assessment.

Hyperactivity of the urease enzyme induces the pathogenesis of peptic ulcers and gastritis. The identification of new urease inhibitors can reduce the activity of urease. Therefore, in the current study, we have evaluated 28 analogues of triazolothiadiazole and triazolothiadiazine heteroaromatics for their in vitro urease inhibitory efficacy. All the tested compounds displayed a remarkable inhibitory potential ranging from 3.33 to 46.83 µM. Among them, compounds 5k and 5e emerged as lead inhibitors with IC50 values of 3.33 ± 0.11 and 3.51 ± 0.49 µM, respectively. The potent inhibitory potential of these compounds was ∼6.5-fold higher than that of the marketed drug thiourea (IC50 = 22.45 ± 0.30 µM). The mechanistic insights from kinetics experiments of the highest potent inhibitors (4g, 5e, and 5k) revealed a competitive type of inhibition with ki values 2.25 ± 0.0028, 3.11 ± 0.0031, and 3.62 ± 0.0034 µM, respectively. In silico modeling was performed to investigate the binding interactions of potent inhibitors with the enzyme active site residues, which strongly supported our experimental results. Furthermore, ADME analysis also showed good druglikeness properties demonstrating the potential of these compounds to be developed as lead antiurease agents.

New supramolecules of bis(acylhydrazones)-linked bisphenol sulfide for Alzheimer's: targeting cholinesterases by in vitro and in silico approaches.

In current research, two functional components, i.e., hydrazone and bisphenol sulfide were combined to get useful supramolecules in medicinal chemistry. Herein 25 new 4,4'-thiodiphenol bis-acylhydrazones were synthesized in good to excellent yields. Initially ethyl-2-chloroacetate was reacted with 4,4'-thiodiphenol, which was further reacted with excess hydrazine hydrate to produce 2,2'-((thiobis(4,1-phenylene))bis(oxy))di(acetohydrazide), which was then combined with various aromatic and aliphatic aldehydes to get the desired products (hydrazones, 4a-4y). The synthesized supramolecules were characterized by contemporary spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectroscopy. The synthetic compound's cholinesterase blocking activity was tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes where compounds 4n, and 4h showed excellent inhibitory potential for AChE, while 4b, and 4h, demonstrated most potent inhibition of BChE. The starting compound (SM3) and compounds 4h and SM3 depicted excellent dual inhibitory capabilities for both enzymes. The chemical basis of anticholinesterase activity was investigated using a structure-based molecular docking approach. The biological significance and the ease of synthesis of this class of compounds should be considered in therapeutic development for Alzheimer's disease treatments.

Substrate-like novel inhibitors of prolyl specific oligo peptidase for neurodegenerative disorders.

Prolyl specific oligopeptidase (POP), is one of the highly expressed enzymes in the brain and is a prime target to treat disorders related to the central nervous system. Here, we describe the structure-based design of the tacrine derivatives, selective, and brain-permeable POP inhibitors. These compounds inactivate POP in-vitro specifically and sustainably at very low concentrations (nano molar). Among this series, compound 6b (IC50 = 0.81 ± 0.04 µM) exhibited most potent inhibition. Furthermore, kinetic study revealed that these molecules target active site of POP which is further confirmed by in-silico molecular interaction analysis. The computational docking results indicates that the compounds are well fitted in the active site with high binding score (i.e., > -7 to > -4 kcal/mol) where Trp595, Arg643, Tyr473, and Ser554 plays important role in binding with the active compounds. The molecular dynamic simulation of most active compounds (6a, 6b, 6d, and 6f) displayed higher free energy binding, when compared to the standard drug in MM-PBSA based binding free energy calculation. In addition, the predicted pharmacokinetic profile suggests that these compounds can serve as excellent inhibitors upon additional optimization which makes them prime choice for further investigation.Communicated by Ramaswamy H. Sarma.

Expression Profiling of the Tripartite Motif Family Genes in Chronic Hepatitis C Patients.

Hepatitis C virus (HCV) is one of the most prevalent pathogens which causes significant morbidity and mortality in 2% of the world's population. Several interferon-stimulated genes (ISGs) are involved in HCV clearance by interacting with the viral proteins. Among these ISGs, the tripartite motif (TRIM) family genes are elevated during HCV infection. This study aims to evaluate the expression of three TRIM family genes in chronic hepatitis C patients, distributed among different groups, including TRIM11, TRIM14, and TRIM25. A total of 242 participants were recruited in this study, including 182 infected patients, 37 naïve individuals, and 23 control individuals. Out of 182 infected patients, 100 achieved sustained virologic response (SVR), 61 achieved rapid virologic response (RVR), and 21 patients developed hepatocellular carcinoma (HCC), showing no response to the given treatments. Our results indicate highest expression levels of TRIM mRNA transcripts in the RVR group with the highest increase of 7.5 folds in TRIM25, 6.68 folds in TRIM14, followed by the data from patients of the SVR group. The elevation was also evident in other groups, i.e., SVR and HCC, in different patterns among all the three TRIM genes. In addition to elevation in expression levels, a linear correlation is observed between the TRIM mRNAs and viral loads of HCV. These results showed the potential role of TRIM family genes in HCV restriction.

Seroprevalence of SARS-CoV-2: Insights into the epidemiology of the pandemic.

AIM: This study aimed to assess the seroprevalence of SARS-CoV-2 and disease symptoms in Malakand, Pakistan. MATERIALS & METHOD: 623 samples with suspected SARS-CoV-2 were collected from different regions of Malakand and analyzed to detect SARS-CoV-2 IgG antibodies using ELISA. RESULTS: 306 (49.1%) 0 f 623 patients were anti-SARS-CoV-2 IgG reactive, with a higher prevalence in males (75%) than females (25%). In this study, we enrolled two groups, subjects working in a non-medical setting and subjects working in a medical setting. Clinical symptoms were statistically linked with SARS-CoV-2. Four weeks of follow-up analysis of IgG titers in health care workers showed an increase in IgG antibodies titer. CONCLUSION: This study gives insights into the community-based spread of SARS-CoV-2 infection, associated immunity, and herd immunity in the studied population. This study can provide insights to the government about early vaccination of this population as most of the population is not yet vaccinated.

Heavy Metals in Vegetables: Screening Health Risks of Irrigation with Wastewater in Peri-Urban Areas of Bhakkar, Pakistan.

One of the key concerns in public health is food security in the food sector. Due to the large amounts of potentially hazardous metals in wastewater, this practice may pose serious environmental and health risks to neighboring residents. In this study, the health effects of heavy metals in vegetables irrigated with wastewater were studied. The findings indicated a massive accumulation of heavy metals in wastewater-irrigated soil and vegetables collected from Bhakkar, Pakistan. The current study looked at the effects of wastewater irrigation on metal buildup in the soil-plant continuum and the health hazards that come with it (Cd, Co, Ni, Mn, Pb, and Fe). Heavy metal concentrations in vegetables cultivated on soil irrigated with untreated wastewater were not significantly lower (p ≥ 0.05) than in vegetables grown on wastewater-irrigated soil and were below the World Health Organization's recommended limits. A considerable amount of the selected hazardous metals was also swallowed by adults and children who consumed these vegetables, according to the research. On soil that had received wastewater irrigation, Ni and Mn were substantially different at p ≥ 0.001 levels. Pb, Ni, and Cd had health risk scores higher than the ones in all ingested vegetables, while Mn had a health risk score greater than the ones in turnips, carrots, and lettuce. The results also showed that both adults and children who consumed these vegetables absorbed a significant amount of the chosen toxic metals. Pb and Cd were shown to be the most dangerous chemical compounds to human health, and everyday consumption of agricultural plants irrigated with wastewater may pose a health risk, according to the health risk criteria.

Bioinformatics and immunoinformatics approach to develop potent multi-peptide vaccine for coxsackievirus B3 capable of eliciting cellular and humoral immune response.

Coxsackievirus B3 (CVB3) is a viral pathogen of various human disorders with no effective preventative interventions. Herein, we aimed to design a chimeric vaccine construct for CVB3 using reverse vaccinology and immunoinformatics approaches by screening the whole viral polyprotein sequence. Firstly, screening and mapping of viral polyprotein to predict 21 immunodominant epitopes (B-cell, CD8+ and CD4+ T-cell epitopes), fused with an adjuvant (Resuscitation-promoting factor), appropriate linkers, HIV-TAT peptide, Pan DR epitope, and 6His-tag to assemble a multi-epitope vaccine construct. The chimeric construct is predicted as probable antigen, non-allergen, stable, possess encouraging physicochemical features, and indicates a broader population coverage (98 %). The tertiary structure of the constructed vaccine was predicted and refined, and its interaction with the Toll-like receptor 4 (TLR4) was investigated through molecular docking and dynamics simulation. Computational cloning of the construct was carried out in pET28a (+) plasmid to guarantee the higher expression of the vaccine protein. Lastly, in silico immune simulation foreseen that humoral and cellular immune responses would be elicited in response to the administration of such a potent chimeric construct. Thus, the design constructed could vaccinate against CVB3 infection and various CVB serotypes. However, further in vitro/in vivo research must assess its safety and effectiveness.

Mediation of an association between neighborhood socioeconomic environment and type 2 diabetes through the leisure-time physical activity environment in an analysis of three independent samples.

INTRODUCTION: Inequitable access to leisure-time physical activity (LTPA) resources may explain geographic disparities in type 2 diabetes (T2D). We evaluated whether the neighborhood socioeconomic environment (NSEE) affects T2D through the LTPA environment. RESEARCH DESIGN AND METHODS: We conducted analyses in three study samples: the national Veterans Administration Diabetes Risk (VADR) cohort comprising electronic health records (EHR) of 4.1 million T2D-free veterans, the national prospective cohort REasons for Geographic and Racial Differences in Stroke (REGARDS) (11 208 T2D free), and a case-control study of Geisinger EHR in Pennsylvania (15 888 T2D cases). New-onset T2D was defined using diagnoses, laboratory and medication data. We harmonized neighborhood-level variables, including exposure, confounders, and effect modifiers. We measured NSEE with a summary index of six census tract indicators. The LTPA environment was measured by physical activity (PA) facility (gyms and other commercial facilities) density within street network buffers and population-weighted distance to parks. We estimated natural direct and indirect effects for each mediator stratified by community type. RESULTS: The magnitudes of the indirect effects were generally small, and the direction of the indirect effects differed by community type and study sample. The most consistent findings were for mediation via PA facility density in rural communities, where we observed positive indirect effects (differences in T2D incidence rates (95% CI) comparing the highest versus lowest quartiles of NSEE, multiplied by 100) of 1.53 (0.25, 3.05) in REGARDS and 0.0066 (0.0038, 0.0099) in VADR. No mediation was evident in Geisinger. CONCLUSIONS: PA facility density and distance to parks did not substantially mediate the relation between NSEE and T2D. Our heterogeneous results suggest that approaches to reduce T2D through changes to the LTPA environment require local tailoring.

In silico scanning of structural and functional deleterious nsSNPs in Arabidopsis thaliana's SOG1 protein, using molecular dynamic simulation approaches.

Suppressor of gamma response 1 (SOG1) is a member of the NAC domain family transcription factors of the DNA damage response (DDR) signaling in the plant's genome. SOG1 is directly involved in transcriptional response to DNA damage, cell cycle checkpoints and ATR or ATM-mediated activation of the DNA damage responses and repair functioning in programmed cell death and regulation of end reduplication. Different mutations in the SOG1 protein lead to severe diseases and, ultimately, cell death. Single nucleotide polymorphisms (SNPs) are an important type of genetic alteration that cause different diseases or programmed cell death. The current study applied different computational approaches to Arabidopsis thaliana L. SOG1 protein to identify the potential deleterious nsSNPs and monitor their impact on the structure, function and protein stability. Various bioinformatics tools were applied to analyze the retrieved 34 nsSNPs and interestingly extracted four deleterious nsSNPs, that is, ensvath13968004 (Q166L), tmp18998388 (P159L), ensvath01103049 (K199N) and tmp18998295 (Y190F). For example, homology modeling, conservation and conformational analysis of the mutant's models were considered to scrutinize the deviations of these variants from the native SOG1 structure. All atoms molecular dynamic simulation confirmed the significance of these mutations on the protein stability, residual and structural conformation, compactness, surface conformation, dominant motion, Gibbs free energy distribution and dynamic effects. Similarly, protein-protein interaction revealed that SOG1 operates as a hub-linking cluster of various proteins, and any changes in the SOG1 might result in the disassociation of several signal transduction cascades.Communicated by Ramaswamy H. Sarma.

Visible Light-Induced Reactive Yellow 145 Discoloration: Structural and Photocatalytic Studies of Graphene Quantum Dot-Incorporated TiO2.

Visible light-induced photocatalytic treatment of organic waste is considered a green and efficient route. This study explored the structural and photocatalytic performance of graphene quantum dot (GQD)-incorporated TiO2 nanocomposites to treat reactive yellow 145 (RY145) dye. For the effective removal of the RY145, efforts were made to better understand the kinetics of the process and optimization of the treatment parameters. Different GQD-doped TiO2 nanocomposites were synthesized employing the sol-gel method. Physicochemical characteristics of the synthesized nanocomposites were studied through FTIR, XRD, UV-visible spectroscopy, SEM, and EDX. Screening studies were conducted for synthesis and reaction optimization. The results indicated that GQD-TiO2 significantly enhanced the photocatalytic discoloration for RY145 dye. Among the synthesized nanocomposites, 15GQD-TiO2 calcined at 300 exhibited 99.3% RY145 discoloration in 30 min under visible light irradiation. Following the pseudo-first-order reaction, the photocatalytic reaction constant K app progressively declined with an increase in the concentration of RY145. The heterogeneous reaction system conformed to the Langmuir-Hinshelwood isotherm, as indicated by the K C (1.08 mg L-1 min-1) and the K LH (0.18 L mg-1) values. O2 •- was found to be the major contributor in GQD-TiO2-300 to decolorize RY154, while TiO2 and GQDs played a vital role in generation of electrons and holes. Additionally, after recycling to the seventh cycle, only 9% decline in photocatalytic performance was observed for the synthesized nanocomposite.

Dysregulation of metalloproteins in ischemic heart disease patients with systolic dysfunction.

Ischemic heart disease (IHD) is the leading cause of mortality worldwide. Metalloproteins have been linked to human health and diseases. The molecular functions of metalloproteins in IHD is not well understood and require further exploration. The objective of this study was to find out the role of metalloproteins in the pericardial fluid of IHD patients having normal (EF > 45) and impaired (EF < 45) left ventricular ejection fraction (LVEF). IHD patients were grouped into two categories: LVEF<45 (n = 12) and LVEF >45 (n = 33). Pooled samples of pericardial fluid were fractionated by using ZOOM-isoelectric focusing (IEF) followed by further processing using one-dimensional gel electrophoresis (1D SDS-PAGE) and filter-aided sample preparation (FASP). Tryptic peptides of each fraction and differential bands were then analyzed by nano-LC-ESI-MS/MS. Protein identification was performed through a Mascot search engine using NCBI-Prot and SwissProt databases. A total of 1082 proteins including 154 metalloproteins were identified. In the differential bands, 60 metalloproteins were identified, while 115 metalloproteins were identified in all ZOOM-IEF fractions. Twelve differentially expressed metalloproteins were selected in the intense bands according to their molecular weight (MW) and isoelectric point (pI). The 12 differentially expressed metalloprotein includes ceruloplasmin, Prothrombin, Vitamin K-dependent protein, Fibulin-1, Ribosomal protein S6 kinase alpha-6, nidogen, partial, Serum albumin, Hemopexin, C-reactive protein, Serum amyloid P-component, and Intelectin-1 protein which were all up-regulated while serotransferrin is the only metalloprotein that was down-regulated in impaired (LVEF<45) group. Among the metalloproteins, Zn-binding proteins are 36.5 % followed by Ca-binging 32.2 %, and Fe-binging 12.2 %. KEGG, pathway analysis revealed the association of ceruloplasmin and serotransferrin with the ferroptosis pathway. In conclusion, 154 metalloproteins were identified of them the Zn-binding protein followed by Ca-binding and Fe-binding proteins were the most abundant metalloproteins. The two metalloproteins, the Cu-binding protein ceruloplasmin, and Fe-binding protein serotransferrin are involved in the ferroptosis pathway, an iron-dependent form of regulated cell death that has been linked to cardiac pathology, especially in IHD patients having impaired systolic (LVEF<45) dysfunction. However, further research is required to validate these findings.

Cold plasma: a promising technology for improving the rheological characteristics of food.

At the beginning of the 21st century, many consumers show interest in purchasing safe, healthy, and nutritious foods. The intent requirement of end-users and many food product manufacturers are trying to feature a new processing technique for the healthy food supply. The non-thermal nature of cold plasma treatment is one of the leading breakthrough technologies for several food processing applications. The beneficial response of cold plasma processing on food quality characteristics is widely accepted as a substitution technique for new food manufacturing practices. This review aims to elaborate and offer crispy innovative ideas on cold plasma application in various food processing channels. It highlights the scientific approaches on the principle of generation and mechanism of cold plasma treatment on rheological properties of foods. It provides an overview of the behavior of cold plasma in terms of viscosity, crystallization, gelatinization, shear stress, and shear rate. Research reports highlighted that the cold plasma treated samples demonstrated a pseudoplastic behavior. The published literatures indicated that the cold plasma is a potential technology for modification of native starch to obtain desirable rheological properties. The adaptability and environmentally friendly nature of non-thermal cold plasma processing provide exclusive advantages compared to the traditional processing technique.