Immunomodulatory Effect of Phytoactive Compounds on Human Health: A Narrative Review Integrated with Bioinformatics Approach.

BACKGROUND: Immunomodulation is the modification of immune responses to control disease progression. While the synthetic immunomodulators have proven efficacy, they are coupled with toxicity and other adverse effects, and hence, the efforts were to identify natural phytochemicals with immunomodulatory potential. OBJECTIVE: The objective of this study is to understand the immunomodulatory properties of various phytochemicals and investigate them in Echinacea species extracts using an in silico approach. METHODOLOGY: Several scientific database repositories were searched using different keywords: "Phytochemicals," "Alkaloids," "Polyphenols," "Flavonoids," "Lectins," "Glycosides," "Tannins," "Terpenoids," "Sterols," "Immunomodulators," and "Human Immune System" without any language restriction. Additionally, the study specifically investigated the immunomodulatory properties of Echinacea species extracts using gene expression analysis of GSE12259 from NCBI-GEO through the Bioconductor package GEOquery and limma. RESULTS: A total of 182 studies were comprehensively analyzed to understand immunomodulatory phytochemicals. The in silico analysis highlighted key biological processes (positive regulation of cytokine production, response to tumor necrosis factor) and molecular functions (cytokine receptor binding, receptor-ligand activity, and cytokine activity) among Echinacea species extracts contributing to immune responses. Further, it also indicated the association of various metabolic pathways, i.e., pathways in cancer, cytokine-cytokine receptor interaction, NF-kappa B, PI3K-Akt, TNF, MAPK, and NOD-like receptor signaling pathways, with immune responses. The study revealed various hub targets, including CCL20, CCL4, GCH1, SLC7A11, SOD2, EPB41L3, TNFAIP6, GCLM, EGR1, and FOS. CONCLUSION: The present study presents a cumulative picture of phytochemicals with therapeutic benefits. Additionally, the study also reported a few novel genes and pathways in Echinacea extracts by re-analyzing GSE 12259, indicating its anti-inflammatory, anti-viral, and immunomodulatory properties.

Exploring the molecular underpinning of psoriasis and its associated comorbidities through network approach: cross talks of genes and pathways.

Patients with psoriasis often complain of several linked disorders including autoimmune and cardiometabolic diseases. Understanding of molecular link between psoriasis and associated comorbidities would be of great interest at the point of patient care management. Integrative unbiased network approach, indicates significant unidirectional gene overlap between psoriasis and its associated comorbid condition including obesity (31 upregulated and 26 downregulated), ischemic stroke (14 upregulated and 2 downregulated), dyslipidaemia (5 upregulated, 5 downregulated), atherosclerosis (8 upregulated and 1 downregulated) and type II diabetes (5 upregulated, 5 downregulated). The analysis revealed substantial gene sharing among the different psoriasis-associated comorbidities. Molecular comorbidity index determining the strength of the interrelation between psoriasis and its comorbidities indicates prevalence of dyslipidaemia followed by type II diabetes among psoriasis patients. The Jaccard coefficient indices revealed psoriasis shared maximum number of biological pathways with dyslipidaemia followed by type 2 diabetes, ischemic stroke, obesity and atherosclerosis. Moreover, pathway annotation highlighted nearly 45 shared pathways amongst psoriasis and its comorbidities and a substantial number of shared pathways was found among multi-morbidities. Overall, the present study established conceivable link between psoriasis and comorbid diseases. The shared genes and overlapped pathways may be explored as a common productive target for psoriasis and its comorbid conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03533-y.

Strongly Coupled Plasmon Polaritons in Gold and Epsilon-Near-Zero Bifilms.

Epsilon-near-zero (ENZ) polaritons in a thin transparent conducting-oxide film exhibit a significant electric field enhancement and localization within the film at frequencies close to their plasma frequency, but do not propagate. Meanwhile, plasmon polariton modes in thin metallic films can propagate for several microns, but are more loosely confined in the metal. Here, we propose a strongly coupled bilayered structure of a thin gold film on a thin indium tin oxide (ITO) film that supports hybrid polariton modes. We experimentally characterize the dispersion of these modes and show that they have propagation lengths of 4-8 µm while retaining mode confinement greater than that of the polariton in gold films by nearly an order of magnitude. We study the tunability of this coupling strength by varying the thickness of the ITO film and show that ultrastrong coupling is possible at certain thicknesses. The unusual linear and nonlinear optical properties of ITO at ENZ frequencies make these bifilms useful for the active tuning of strong coupling, ultrafast switching, and enhanced nonlinear interactions at near-infrared frequencies.

Suppression of Nonlinear Optical Rogue Wave Formation Using Polarization-Structured Beams.

A nonlinear self-focusing material can amplify random small-amplitude phase modulations present in an optical beam, leading to the formation of amplitude singularities commonly referred to as optical caustics. By imposing polarization structuring on the beam, we demonstrate the suppression of amplitude singularities caused by nonlinear self-phase modulation. Our results are the first to indicate that polarization-structured beams can suppress nonlinear caustic formation in a saturable self-focusing medium and add to the growing understanding of catastrophic self-focusing effects in beams containing polarization structure.

The interaction analysis between human serum albumin with chlorpyrifos and its derivatives through sub-atomic docking and molecular dynamics simulation techniques.

Chlorpyrifos (CPF) is an extensively used organophosphate pesticide for crop protection. However, there are concerns about it contaminating the environment and human health, with estimated three lakh deaths annually. The molecular modeling protocol was assisted in redesigning thirteen well-known CPF linkers and inserting them at five selectable CPF (R1-R5) positions of CPF to get 258 CPF derivatives. CPF and its derivatives were optimized using LigPrep and docked to a grid centralized on Trp214 using extra precision glide docking. The Binding free energy of complexes was calculated using molecular mechanics/generalized born surface area (MM-GBSA). CPF and CPFD-225 have glide scores of - 3.08 and - 6.152 kcal/mol, respectively, with human serum albumin and ΔG bind for CPF (- 33.041817 kcal/mol) (- 52.825 kcal/mol) for CPF-D225. The top ten CPF derivatives showed at least ninefold better binding free energy than the CPF proposed for polyclonal antibody production. Subsequently, molecular docking studies revealed that CPF and its derivatives could bind to human serum albumin (HSA). Furthermore, using the Desmond package, a 100-ns molecular dynamics (MD) simulation was performed on the potential binding site. The final systems of CPF-HSA and CPF-222D complexes consist of 76,014 and 76,026 atoms, respectively. The physical stability of both the systems (CPF-HSA and CPF-222D) was analyzed by considering the overall potential energy, RMSF, RMSD, Hydrophobic interactions, and water-mediated patterns, which showed total energy of - 141,610 kcal/mol and - 140,150 kcal/mol, respectively. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03344-7.

Transcriptomic landscaping of core genes and pathways of mild and severe psoriasis vulgaris.

Psoriasis is a common chronic inflammatory skin disease affecting >125 million individuals worldwide. The therapeutic course for the disease is generally designed upon the severity of the disease. In the present study, the gene expression profile GSE78097, was retrieved from the National Centre of Biotechnology (NCBI)­Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) in mild and severe psoriasis using the Affy package in R software. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways of the DEGs were analysed using clusterProfiler, Bioconductor, version 3.8. In addition, the STRING database was used to develop DEG­encoded proteins and a protein­protein interaction network (PPI). Cytoscape software, version 3.7.1 was utilized to construct a protein interaction association network and analyse the interaction of the candidate DEGs encoding proteins in psoriasis. The top 2 hub genes in Cytohubba plugin parameters were validated using immunohistochemical analysis in psoriasis tissues. A total of 382 and 3,001 dysregulated mild and severe psoriasis DEGs were reported, respectively. The dysregulated mild psoriasis genes were enriched in pathways involving cytokine­cytokine receptor interaction and rheumatoid arthritis, whereas cytokine­cytokine receptor interaction, cell cycle and cell adhesion molecules were the most enriched pathways in severe psoriasis group. PL1N1, TLR4, ADIPOQ, CXCL8, PDK4, CXCL1, CXCL5, LPL, AGT, LEP were hub genes in mild psoriasis, whereas BUB1, CCNB1, CCNA2, CDK1, CDH1, VEGFA, PLK1, CDC42, CCND1 and CXCL8 were reported hub genes in severe psoriasis. Among these, CDC42, for the first time (to the best of our knowledge), has been reported in the psoriasis transcriptome, with its involvement in the adaptive immune pathway. Furthermore, the immunoexpression of CDK1 and CDH1 proteins in psoriasis skin lesions were demonstrated using immunohistochemical analysis. On the whole, the findings of the present integrated bioinformatics and immunohistochemical study, may enhance our understanding of the molecular events occurring in psoriasis, and these candidate genes and pathways together may prove to be therapeutic targets for psoriasis vulgaris.

Fusarium head blight in wheat: contemporary status and molecular approaches.

Fusarium head blight (FHB) disease that occurs in wheat is caused by Fusarium graminearum and is a major risk to wheat yield. Although several research efforts focusing on FHB have been conducted in the past several decades, conditions have become more critical due to the increase in its virulent forms. In such a scenario, conferring complete resistance in plants seems to be difficult for handling this issue. The phenotyping for FHB and finding a solution for it at the genetic level comprises a long-term process as FHB infection is largely affected by environmental conditions. Modern molecular strategies have played a crucial role in revealing the host-pathogen interaction in FHB. The integration of molecular biology-based methods such as genome-wide association studies and marker-based genomic selection has provided potential cultivars for breeding programs. In this review, we aim at outlining the contemporary status of the studies conducted on FHB in wheat. The influence of FHB in wheat on animals and human health is also discussed. In addition, a summary of the advancement in the molecular technologies for identifying and developing the FHB-resistant wheat genetic resources is provided. It also suggests the future measures that are required to reduce the world's vulnerability to FHB which was one of the main goals of the US Wheat and Barley Scab Initiative.

Decoding Psoriasis: Integrated Bioinformatics Approach to Understand Hub Genes and Involved Pathways.

BACKGROUND: Psoriasis is a chronic immune mediated skin disorder with global prevalence of 0.2- 11.4%. Despite rare mortality, the severity of the disease could be understood by the accompanying comorbidities, that has even led to psychological problems among several patients. The cause and the disease mechanism still remain elusive. OBJECTIVE: To identify potential therapeutic targets and affecting pathways for better insight of the disease pathogenesis. METHOD: The gene expression profile GSE13355 and GSE14905 were retrieved from NCBI, Gene Expression Omnibus database. The GEO profiles were integrated and the DEGs of lesional and non-lesional psoriasis skin were identified using the affy package in R software. The Kyoto Encyclopaedia of Genes and Genomes pathways of the DEGs were analyzed using clusterProfiler. Cytoscape, V3.7.1 was utilized to construct protein interaction network and analyze the interactome map of candidate proteins encoded in DEGs. Functionally relevant clusters were detected through Cytohubba and MCODE. RESULTS: A total of 1013 genes were differentially expressed in lesional skin of which 557 were upregulated and 456 were downregulated. Seven dysregulated genes were extracted in non-lesional skin. The disease gene network of these DEGs revealed 75 newly identified differentially expressed gene that might have a role in development and progression of the disease. GO analysis revealed keratinocyte differentiation and positive regulation of cytokine production to be the most enriched biological process and molecular function. Cytokines -cytokine receptor was the most enriched pathways. Among 1013 identified DEGs in lesional group, 36 DEGs were found to have altered genetic signature including IL1B and STAT3 which are also reported as hub genes. CCNB1, CCNA2, CDK1, IL1B, CXCL8, MKI 67, ESR1, UBE2C, STAT1 and STAT3 were top 10 hub gene. CONCLUSION: The hub genes, genomic altered DEGs and other newly identified differentially dysregulated genes would improve our understanding of psoriasis pathogenesis, moreover, the hub genes could be explored as potential therapeutic targets for psoriasis.

Psoriasis and cardiovascular disorders: association or epiphenomenon? Meta-analysis of observational studies.

Psoriasis is a chronic inflammatory disease believed to be correlated with numerous cardiovascular risk factors including increased blood pressure, elevated blood cholesterol level, diabetes, inactivity, high body mass index (obesity) and dyslipidaemia. The present meta-analysis intends to assess the association between psoriasis and cardiovascular risk factors. Three hundred and fifty articles were primarily screened using NCBI MEDLINE/PubMed and Cochrane library from its inception until June 30, 2018. Of these, 26 observational studies depending upon the inclusion and exclusion criteria were included in the study with 17,672 psoriasis patients and 66,407 non-psoriasis subjects. The psoriasis patients were found to be at significantly increased risk of systolic blood pressure (SBP) [ORs 2.31 (95% CI 1.12, 4.74)], diastolic blood pressure (DBP) [ORs 2.31 (95% CI 1.58, 3.38)], abdominal obesity [ORs 1.90 (95% CI 1.45, 2.50)] and triglycerides [ORs 1.80 (95% CI 1.29, 2.51)] as compared to non-psoriasis subjects. The subgroup analyses of studies based on the continents revealed that psoriasis patients from Middle East are prone to higher risk factors of CVD including increased levels of triglyceride, cholesterol, DBP, SBP, fasting blood sugar, body mass index and decreased HDL levels, whereas psoriasis patients from European population reported increased LDL-C and waist circumference. The present study supports a significant association between psoriasis and incidence of major adverse cardiovascular events. Contrary to the previous literature, our finding suggests that hypertension is a highly associative condition in psoriasis. The findings of this study could be validated amongst well-defined cohorts of patients with psoriasis individually in different regions to confirm the implication of the study.

The Association of Metabolic Syndrome and Psoriasis: A Systematic Review and Meta-Analysis of Observational Study.

BACKGROUND: Metabolic syndrome worsens complications in psoriasis patients by predisposing them to cardiovascular diseases. Psoriasis has been widely associated with metabolic syndrome; however, it has still not been proven owing to a limited number of studies and some of those reporting conflicting results. OBJECTIVE: Psoriasis has reportedly been associated with metabolic syndrome; however, it has yet not been established beyond doubt owing to conflicting literature. The present meta-analysis of observational studies aims to evaluate the prevalence of metabolic syndrome in psoriasis patients and establish an inferring point that psoriasis patients are certainly susceptible to metabolic syndrome. The study will benefit clinicians to assess and monitor psoriasis patients for several associated comorbid conditions and in its treatment. METHODS: A systematic web search for 'Psoriasis', 'Metabolic Syndrome', 'Hypertension', 'Plasma Glucose', 'Dyslipidaemia', 'Waist Circumference' was performed, collecting all original observational studies on humans up to April 30, 2018. Depending on the inclusion and exclusion criteria, articles were screened for eligibility. Due to the presence of significant heterogeneity, the Odds Ratio (OR) was calculated using a random-effect model with Der-Simonian and Laird method. The statistical heterogeneity was determined using I2 statistics. Comprehensive Meta-Analysis Software, Version 3 was used to perform all the analysis. RESULTS: Sixty-three studies encompassing 15,939 psoriasis patients and 103,984 controls were included in this meta-analysis. Among them, 30.29 % of psoriasis patients were reported with metabolic syndrome in comparison to 21.70 % of subjects in the control group. The present study clearly indicates an increased prevalence of metabolic syndrome among psoriasis patients (OR: 2.077 [95% CI, 1.84 - 2.34]). CONCLUSION: The findings support the fact that psoriasis patients have a higher incidence of metabolic syndrome. Our study also recommends that psoriasis patients should be regularly monitored for metabolic syndrome complications and its associated risk factors such as hypertension, raised triglyceride, lowered HDL Cholesterol, increased fasting plasma glucose, and waist circumference.

Measurement of the radial mode spectrum of photons through a phase-retrieval method.

We propose and demonstrate a simple and easy-to-implement projective-measurement protocol to determine the radial index p of a Laguerre-Gaussian (LGpl) mode. Our method entails converting any specified high-order LGp0 mode into a near-Gaussian distribution that matches the fundamental mode of a single-mode fiber (SMF) through the use of two phase screens (unitary transforms) obtained by applying a phase-retrieval algorithm. The unitary transforms preserve the orthogonality of modes before the SMF and guarantee that our protocol can, in principle, be free of crosstalk. We measure the coupling efficiency of the transformed radial modes to the SMF for different pairs of phase screens. Because of the universality of phase-retrieval methods, we believe that our protocol provides an efficient way of fully characterizing the radial spatial profile of an optical field.