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Gusperimus is an anti-inflammatory drug that has shown to be effective in managing autoimmunity and preventing graft rejection. This is unstable and easily broken down into cytotoxic components. We encapsulated gusperimus binding it covalently to squalene obtaining squalene-gusperimus nanoparticles (Sq-GusNPs). These nanoparticles enhanced the immunosuppressive effect of gusperimus in both mouse macrophages and T cells. The half-maximal inhibitory concentration in macrophages was 9-fold lower for Sq-GusNPs compared with the free drug. The anti-inflammatory effect of the Sq-GusNPs was maintained over time without cytotoxicity. By studying nanoparticles uptake by cells with flow cytometry, we demonstrated that Sq-GusNPs are endocytosed by macrophages after binding to low-density lipoprotein receptors (LDLR). In presence of cathepsin B or D release of gusperimus is increased demonstrating the participation of proteases in the release process. Our approach may allow the application of Sq-GusNPs for effective management of inflammatory disorders including autoimmunity and graft rejection.

The profitability of the olive flounder (Paralichthys olivaceus) aquaculture industry in Korea depends on high production and maintenance of flesh quality, as consumers prefer to eat raw flounders from aquaria and relish the raw muscles as ‘sashimi’. For sustaining high production, easy-to-deliver and efficient vaccination strategies against serious pathogens, such as viral hemorrhagic septicemia virus (VHSV), is very important as it cause considerable losses to the industry. Whereas, a safe and non-invasive vaccine formulation that is free from unacceptable side-effects and does not devalue the fish is needed to maintain flesh quality. We previously developed a squalene–aluminium hydroxide (Sq + Al) adjuvanted VHSV vaccine that conferred moderate to high protection in flounder, without causing any side effects when administered through the intraperitoneal (IP) injection route. However, farmers often demand intramuscular (IM) injection vaccines as they are relatively easy to administer in small fishes. Therefore, we administered the developed vaccine via IP and IM routes and investigated the safety and persistency of the vaccine at the injection site. In addition, we conducted a comparative analysis of vaccine efficacy and serum antibody response. The clinical and histological observation of the IM and IP groups showed that our vaccine remained persistence at the injection sites for 10–17 weeks post vaccination (wpv), without causing any adverse effects to the fish. The relative percentage of survival were 100% and 71.4% for the IP group and 88.9% and 92.3% for the IM group at 3 and 17 wpv, respectively. Thus, considering the persistency period (24 wpv) and both short and long-term efficacy of our vaccine, the present study offers an option to flounder farmers in selecting either IM or IP delivery strategy according to their cultured fish size and harvesting schedule — IM vaccination for small-sized fish and IP vaccination for table-sized fish.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the coronavirus disease 2019 (COVID-19) has afflicted tens of millions of people in a worldwide pandemic. A recently developed recombinant Plant-Derived Virus-Like Particle Vaccine candidate for COVID-19 (CoVLP) formulated with AS03 has been shown to be well-tolerated and highly immunogenic in healthy adults. Since the target population for the vaccine includes women of childbearing potential, the objective of the study was to evaluate any untoward prenatal and postnatal effects of AS03-adjuvanted CoVLP administered intramuscularly to Sprague-Dawley female rats before cohabitation for mating (22 and 8 days prior) and during gestation (Gestation Days [GD] 6 and 19). The embryo-fetal development (EFD) cohort was subjected to cesarean on GD 21 and the pre/post-natal (PPN) cohort was allowed to naturally deliver. Effects of AS03-adjuvanted CoVLP was evaluated on pregnant rats, embryo-fetal development (EFD), during parturition, lactation and the development of the F1 offspring up to weaning Vaccination with AS03-adjuvanted CoVLP induced an antibody response in F0 females and anti-SARS-CoV-2 spike-specific maternal antibodies were detected in the offspring at the end of the gestation and lactation periods. Overall, there was no evidence of untoward effects of AS03-adjuvanted CoVLP on the fertility or reproductive performance of the vaccinated F0 females. There was no evidence of untoward effects on embryo-fetal development (including teratogenicity), or early (pre-weaning) development of the F1 offspring. These results support the acceptable safety profile of the AS03-adjuvanted CoVLP vaccine for administration to women of childbearing potential.

Background Vaccines are the main prophylactic measure against pandemic influenza. Adjuvanted, cell culture–derived vaccines, which are not subject to limitations of egg-based vaccine production, have the potential to elicit an antibody response against heterologous strains and may be beneficial in the event of an A/H5N1 pandemic. Methods A prespecified exploratory analysis of data from a phase 2, randomized, controlled, observer-blind multicenter trial (NCT01776554) to evaluate the immunogenicity of a MF59-adjuvanted, cell culture–based A/H5N1 influenza vaccine (aH5N1c), containing 7.5 µg hemagglutinin antigen per dose, in subjects 6 months through 17 years of age was conducted. Geometric mean titers (GMT) were determined using hemagglutination inhibition (HI) and microneutralization (MN) assays, and proportions of patients achieving seroconversion, HI and MN titers ≥ 1:40, and a 4-fold increase in MN titers against 5 heterologous strains (influenza A/H5N1 Anhui/2005, Egypt/2010, Hubei/2010, Indonesia/2005, and Vietnam/1203/2004) three weeks after administration of the second dose were assessed. Results After the second dose, HI GMTs against heterologous strains increased between 8- and 40-fold, and MN GMTs increased 13- to 160-fold on Day 43 vs Day 1. On Day 43, 32–72% of subjects had HI titers ≥ 1:40 and achieved seroconversion against the heterologous strains. Using the MN assay, 84–100% of subjects had MN titers ≥ 1:40 and 83–100% achieved an at least 4-fold increase in MN titers against the heterologous strains. The highest responses were consistently against A/H5N1 Egypt/2010. Conclusions When given to children aged 6 months through 17 years, aH5N1c resulted in increased immunogenicity from baseline against all 5 heterologous A/H5N1 strains tested, demonstrating the potential of an MF59-adjuvanted, cell-derived A/H5N1 vaccine to provide cross-protection against other A/H5N1 strains (NCT01776554).

Transcriptional downregulation is widely used for metabolic flux control. Here, marO, a cis-element of Escherichia coli mar operator, was explored to engineer promoters of Saccharomyces cerevisiae for downregulation. First, the ADH1 promoter (PADH1) and its enhanced variant PUADH1 were engineered by insertion of marO into different sites, which resulted in decrease in both gfp5 transcription and GFP fluorescence intensity to various degrees. Then, marO was applied to engineer the native ERG1 and ERG11 promoters due to their importance for accumulation of value-added intermediates squalene and lanosterol. Elevated squalene content (4.9-fold) or lanosterol content (4.8-fold) and 91 or 28% decrease in ergosterol content resulted from the marO-engineered promoter PERG1(M5) or PERG11(M3), respectively, indicating the validity of the marO-engineered promoters in metabolic flux control. Furthermore, squalene production of 3.53 g/L from cane molasses, a cheap and bulk substrate, suggested the cost-effective and promising potential for squalene production.

Vaccination is the most effective approach to reduce the substantial morbidity and mortality caused by influenza infection. Vaccine efficacy is highly sensitive to antigenic changes causing differences between circulating and vaccine viruses. Adjuvants such as MF59 increase antibody-mediated cross-reactive immunity and therefore may provide broader seasonal protection. A recent clinical trial showed that an MF59-adjuvanted vaccine was more efficacious than a nonadjuvanted comparator in subjects < 2 years of age, although not in those ≥ 2 years, during influenza seasons in which the predominant circulating virus was an A/H3N2 strain that was antigenically different from the vaccine virus. This finding suggested that the increased efficacy of the adjuvanted vaccine in younger subjects may be mediated by strain cross-reactive antibodies. A subset of the trial population, representing subjects with distinct age and/or immunological history, was tested for antibody responses to the vaccine A/H3N2 strain as well as A/H3N2 drifted strains antigenically matching the viruses circulating during the trial seasons. The neutralizing tests showed that, compared with nonadjuvanted vaccine, the adjuvanted vaccine improved not only the neutralizing antibody response to the vaccine strain but also the cross-reactive antibody response to the drifted strains in subjects with lower preexisting antibody titers, regardless of their age or vaccine history. The results demonstrated an immunological benefit and suggested a potential efficacy benefit by adjuvanted vaccine in subjects with lower preexisting antibody responses.

Heavy metal toxicity and drought stresses are two growing concerns of the global population as these have a disastrous effect on the agriculture sector, creating oxidative stress in plants and leads to deleterious effects, which end up causing a major decline in yield. Hence, carving out the best candidate for combating both these stresses have become the prime objective of researchers. Plectranthus amboinicus (Lour.) Spreng., a medicinal plant, is regarded as one such candidate that can tolerate both drought and zinc stressors by the elicitation of metabolic changes. Variation in the composition of primary and secondary metabolites of P. amboinicus was evaluated in the leaf tissues of the plants subjected to drought and ZnSO4 (4 mM) treatments. Drought stress resulted in the accumulation of amino acids and sugars in the leaves of plants exposed to this stress. Similarly, zinc stress exhibited a remarkable impact on the synthesis of secondary metabolites like alkaloids, phenols, and flavonoids. Further, on carrying out GC–MS profiling, the compositional variation of secondary metabolites produced in P. amboinicus implicated its inherent potential to survive environments of these two stresses. Compounds like 2-methoxy-4-ethyl-6-methylphenol, gamma-sitosterol, hexadecanoic acid, alpha-amyrin, and ethyl linalool were some of the major secondary metabolites developed in leaves of plants under drought, whereas during ZnSO4 treatment, the major compounds developed were trans-alpha-bergamotene, squalene, 1,5-dimethyl-1-vinyl-4-hexenyl isovalerate, and spathulenol. This in turn makes the plant more compatible with the stressful environmental conditions, aiding it with better survival and protection. At the same time, the enhancement in the content of these metabolites in this medicinal plant under the influence of these stressors may have applications in the pharmaceutical industry, necessary for the development of novel drugs.

PURPOSE: The enzyme Cyclooxygenases (COX-1 and COX-2) catalyze the formation of prostaglandin, a mediator of the inflammatory pathway. Inflammation related pathological conditions may be alleviated by targeting the Cox enzymes.COX-2 inhibitors that are currently available in the market causes undesirable side effects. Our present study focuses on the in-silico inhibition of COX -2 enzyme by the phytocompounds from Albizia amara and Phyla nodiflora. METHODS: The phytochemicals present in Albizia amara and Phyla nodiflora were analyzed for their COX-2 inhibition potential. Eight compounds from Albizia amara and eleven compounds from Phyla nodiflora obtained from GC–MS analysis was used for the current study. Molecular docking was performed using AutoDock vina. The crystal structure of COX-2 (PDB ID: 5IKR) was obtained from Protein data bank. PyMol was used to remove any solvent, organic and inorganic molecules. Energy minimization of the protein was carried out using SPDBV software. Geometrical optimizations of the ligands were performed using Avogadro software. Celecoxib was used as the positive control. ADMET properties of the compounds were analyzed using SwissADME and ProtoxII online servers. Molecular mechanics/generalized born surface area (MM/GBSA) calculations were performed to evaluate the binding efficiency. Molecular dynamics of the protein and protein–ligand complex was studied for about 100 ns using Desmond package of Schrodinger suite. RESULTS: Among the eighteen compounds, Squalene present in both the plants showed a better binding energy of -7.7 kcal/mol, when compare to other phytocompounds present in the extract. The control celecoxib showed a binding energy of about – 9.4 kcal/mol. The toxicity and ADMET properties of squalene indicated that it is non-toxic and followed Lipinski’s rule. Molecular Dynamics (MD) analysis showed that the binding of squalene to the enzyme was stable. CONCLUSION: Squalene could potentially inhibit COX2 and o wing to its properties, squalene can be formulated in gels/creams and could be possibly used for external edema and inflammation GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40199-021-00408-6.

Summary Background The absolute degree of protection from influenza vaccines in older adults has not been studied since 2001. This study aimed to show the clinical efficacy of an MF59-adjuvanted quadrivalent influenza vaccine (aQIV) in adults 65 years or older compared with adults not vaccinated to prevent influenza. Methods We did a randomised, stratified, observer-blind, controlled, multicentre, phase 3 study at 89 sites in 12 countries in 2016–17 northern hemisphere and 2017 southern hemisphere influenza seasons. We enrolled community-dwelling male and female adults aged 65 years and older who were healthy or had comorbidities that increased their risk of influenza complications. We stratified eligible participants by age (cohorts 65–74 years and ≥75 years) and risk of influenza complications (high and low) and randomly assigned them (1:1) via an interactive response technology to receive either aQIV or a non-influenza comparator vaccine. We masked participants and outcome assessors to the administered vaccine. Personnel administering the vaccines did not participate in endpoint assessment. The primary outcome was absolute vaccine efficacy assessed by RT-PCR-confirmed influenza due to any influenza strain in the overall study population (full analysis set) from day 21 to 180 or the end of the influenza season. Vaccine efficacy was calculated on the basis of a Cox proportional hazard regression model for time to first occurrence of RT-PCR-confirmed influenza due to any strain of influenza. Safety outcomes were assessed in the overall study population. This trial was registered with ClinicalTrials.gov , NCT02587221 . Findings Northern hemisphere enrolment occurred between Sept 30, 2016, and Feb 28, 2017, and southern hemisphere enrolment between May 26, 2017, and 30 June 30, 2017. aQIV was administered to 3381 participants, who subsequently had 122 (3·6%) RT-PCR-confirmed influenza cases, and the comparator was administered to 3380 participants, who subsequently had 151 (4·5%) influenza cases. The majority, 214 (78·4%) of 273, were caused by influenza A H3N2. Most antigenically characterised isolates were mismatched to the vaccine strain (118 [85%] of 139). Vaccine efficacy was 19·8% (multiplicity-adjusted 95% CI −5·3 to 38·9) against all influenza and 49·9% (−24·0 to 79·8) against antigenically matched strains, when the protocol definition of influenza-like illness was used. The most common local solicited adverse event was injection site pain, reported by 102 (16·3%) of 624 participants in the aQIV group and 71 (11·2%) of 632 of participants in the comparator group. Deaths were evenly distributed; none were considered related to study vaccines. The safety profile for aQIV was similar to previously reported trials. Interpretation The prespecified criterion for showing the efficacy of aQIV in older adults was not met during the influenza seasons with high amounts of vaccine strain mismatch. Vaccine efficacy was higher against influenza cases associated with higher fever, which represent more clinically significant disease. Funding Seqirus UK.

The oil palm (Elaeis guineensis) fruit is a source of vegetable oil and various phytonutrients. Phytochemical compounds present in palm oil include tocotrienols, carotenoids, phytosterols, squalene, coenzyme Q10, and phospholipids. Being a fruit, the oil palm is also a rich source of water-soluble phytonutrients, including phenolic compounds. Extraction of phytonutrients from the oil palm vegetation liquor of palm oil milling results in a phenolic acid-rich fraction termed Water-Soluble Palm Fruit Extract (WSPFE). Pre-clinical in vitro, ex vivo, and in vivo studies carried out using various biological models have shown that WSPFE has beneficial bioactive properties, while clinical studies in healthy volunteers showed that it is safe for human consumption and confers antioxidant and anti-inflammatory effects. The composition, biological properties, and relevant molecular mechanisms of WSPFE discovered thus far are discussed in the present review, with a view to offer future research perspectives on WSPFE for health and non-health applications.

Methotrexate (MTX), an antifolate drug, is extensively prescribed for patients suffering from diseases like cancer, psoriasis, neoplasms, and rheumatoid arthritis. Despite its effectiveness, MTX sometimes finds limited application because its undesirable side effects, including hepatic or renal impairment, bone marrow toxicity and gastrointestinal mucosal injury. Squalene, a highly unsaturated isoprenoid compound, isolated from shark liver oil has great potential in neutralizing the damaging effects triggered by free radicals. Therefore, in this study, the protective role of dietary squalene supplementation on oxidative stress induced by methotrexate in experimental rats was evaluated. A significant reduction was displayed in the activities of catalase (CAT) and superoxide dismutase (SOD) in MTX-intoxicated groups compared to other groups. Similarly, the activities of glutathione dependant enzymes (GPx and GST) and reduced glutathione (GSH) in MTX-induced groups were shown to be lower compared to the untreated control. Increased LPO (lipid peroxide) level was found in MTX-intoxicated groups compared to other groups. In addition, alterations in the levels of liver marker enzymes like AST, ALP, ALT, and LDH were noticed in MTX intoxicated groups compared to other groups. Biochemical results were confirmed by the histopathological examination of liver sections. In conclusion, the result obtained in the present study proposes that squalene exerts antioxidant activity and is capable of ameliorating oxidative stress and liver injury induced by MTX.

Background Wrightia tinctoria R.Br. (Apocyanaceae) is known as a biologically effective plant for the treatment of jaundice in the Indian traditional system of medicine. It is a wild medicinal tree possessing anti-inflammatory, antidiabetic, antinociceptive, hepatoprotective, antibacterial, antifungal, antiviral, antipsoriatic, anticancerous, anthelmintic, aphrodisiac, analgesic, and antipyretic activities. Its constituents are of utmost interest to pharmaceutical industries owing to their many actions and biological activities. Method Methanolic extract of W. tinctoria (MEWT) was investigated by gas chromatography-mass spectroscopy and provided affirmative results assisting in the identification and characterization of therapeutic claims regarding this species in the traditional system. The antioxidant activity of MEWT was determined by the most suitable DPPH method. Results The basic compounds found in MEWT were β-caryophyllene (0.22%), mome inositol (12.02%), neophytadiene (1.61%), eicosanoic acid methyl ester (0.32%), 8,11,14-eicosatrienoic acid methyl ester (0.60%), phytol (0.94%), phytol palmitate (1.37%), squalene (1.57%), flavone 4-OH, 5-OH, 7-di-O-glucoside (29.34%), γ-tocopherol (0.49%), stigmast-5-en-3-ol (3.14%), methyl commate B (1.76%), methyl commate A (5.20%), and 24-norursa-3,12-diene (20.36%). The obtained results in the analysis of antioxidant activity of MEWT exhibited considerable free radical scavenging capacity against DPPH-generated free radicals. Conclusions This study expands the knowledge of MEWT chemical composition and provides evidence to substantiate ethno-medicinal use of the plant by exploring antioxidant activity. The substantial antioxidant activity of MEWT could be due to presence of terpenes, flavonoids, vitamin E, and other reported compounds. Highlights This study includes identification of phytochemicals and antioxidant potential of methanolic extract of Wrightia tinctoria, assisting in therapeutic claims regarding this species in the traditional system.

Head lice (Pediculus humanus capitis) are worldwide obligate human ectoparasites, with high implications in pediatrics. In Europe, first-line topical neurotoxic insecticidal therapeutic strategies are being replaced by topical physically acting agents as the first-choice treatment. Safety of the active ingredients and high efficacy in a one-time single-dose treatment with a brief treatment application time are key issues for consumer use and effective compliance. The aim of this study was to assess the in vitro efficacy of a newly developed squalane and dimethicone-based pediculicidal formula, against motile head lice and eggs after 2 and 5 min immersion in the product, as well as its skin tolerance and acceptability under dermatological and pediatric expert control in children with atopic skin. The results indicate that at both time points, 100% mortality rate of head lice crawling stages and latest age eggs was achieved. The formula was well tolerated and suitable for children with atopic skin from 12 months of age. Showing high in vitro efficacy and good skin acceptability, this solution is presented as a new safe alternative therapy for treatment of head lice infestations. This work was funded by Ferrer International S.A., the company that developed the human head louse treatment discussed in this paper. This solution is marketed as “OTC ANTIPIOJOS FORMULA TOTAL” by Ferrer International S.A. in Spain.

Astragaloside VII (AST-VII), a major cycloartane saponin isolated from Turkish Astragalus species, turned out to be one of the most active metabolites demonstrating Th1/Th2 balanced immune response. As Quillaja saponins are extensively used in adjuvant systems, this study made an attempt to improve AST-VII based adjuvant systems by using different immunostimulatory/delivery agents (monophosphoryllipid A (MPL), Astragalus polysaccharide (APS) and squalene) and to induce cellular and humoral immune response against a viral vaccine. For this purpose, Newcastle Disease vaccine (NDV) was chosen as a model vaccine. Swiss albino mice were immunized subcutaneously with LaSota vaccines in the presence/absence of AST-VII or developed adjuvant systems. AST-VII administration both in live/inactivated LaSota vaccines induced neutralizing and NDV specific IgG, IgG1 and IgG2b antibodies response as well as IL-2 and IL-4 production. APS based delivery systems enhanced the production of neutralizing antibody and the minor augmentation of IFN-? and IL-2 levels. Squalene emulsion (SE) alone or combined with AST-VII were effective in NDV restimulated splenocyte proliferation. As a conclusion, AST-VII and AST-VII containing adjuvant systems demonstrated Th1/Th2 balanced antibody and cellular immune responses in NDV vaccines. Thus, these systems could be developed as vaccine adjuvants in viral vaccines as alternative to saponin-based adjuvants. © 2021 International Alliance for Biological Standardization, 1139B411402292 Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK, This study partially supported by The Scientific and Technological Research Council of Turkey (TUBITAK) under Grant 1139B411402292 .

Squalene, a triterpenoid compound is proven to possess immense bioactivities by virtue of its high antioxidant activity. The present study was designed to investigate the quality attributes of muffins as influenced by addition of encapsulated squalene. Nutritional analysis showed that calorific value of prepared muffins has ranged from 480.78 ± 0.10 to 501.61 ± 0.38 kcal. Baking loss was lowest in case of muffins prepared with encapsulated squalene with its crumb region recorded higher moisture content. Color kinetics study indicated that browning index (BI) was higher in crust portion of encapsulated squalene enriched muffins. Scanning electron micrographs showing that muffins with encapsulated squalene had stronger structural organization. This was further supported by the textural studies showed that the muffins with encapsulated squalene was cohesive, springier and chewy with less gumminess and stiffness indicating their efficacy in improving the textural quality. Oxidative stability and microbiological quality were also high in squalene enriched foods suggesting that squalene might have some antimicrobial effects. Outcome of the study indicated that encapsulated squalene can be very well utilised as a functional food ingredient in ready -to-eat functional foods. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1007/s13197-020-04955-9).

Aralia elata (Miq.) Seem is widely used as a medicinal plant and functional food in China. In this study, A. elata plants were exposed to full sunlight (CK), 40% shading (LS), 60% shading (MS), and >80% shading (ES) condition to investigate the effects of shading treatments on growth, stress levels, antioxidant enzymes activity, araloside content and related gene expression. The greatest growth and leaf biomass were achieved in 40% shading, and leaf biomass per plant increased by 16.09% compared to the non-shading treatment. Furthermore, the lowest reactive oxide species (ROS) production and lipid peroxidation resulting from increasing antioxidant enzyme activity were also observed in LS treatment. Overall, shading percentage negatively regulated the expression of key enzymes (squalene synthase, SS; squalene epoxidase, SE and β-amyrin synthase, bAS) involved in the saponin biosynthesis, resulting in the greatest yields of total and four selected aralosides in A. elata leaves were achieved in sunlight group. However, the greatest yield of total saponin in the leaves was observed in the 40% shading group due to higher leaf biomass. The results suggest that optimizing the field growing conditions would be important for obtaining the greatest yield of bioactive components. Total saponin and selected aralosides also have a significant correlation with ROS production and antioxidant enzyme activity, these indicated the increased yield of these saponins may be part of a defense response. The study concludes that the production of saponin was the interaction of oxidative stress and photosynthesis.

Objective: The aim of this study was to investigate the chemical compound of the antioxidant activity of the extract from andaliman fruit (Zanthoxylum acanthopodium DC.) and the quality parameters and the total flavonoid determination of the highest antioxidant activity. Methods: The andaliman fruits were extracted using a solvent such as n-hexane, ethyl acetate and 70% ethanol obtained extracts, follow the antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The quality parameters and total flavonoid determination were performed from highest antioxidant activity. Fractionated was done using vacuum liquid chromatography (VLC) with the mobile phase chloroform-methanol (9:1 ~1:9). Purification with Thin Layer Chromatography (TLC) preparative, identification using UV-spectrophotometry, FTIR, Gas chromatography Mass Spectrometry (GCMS) analysis. Results: The 70% of ethanol has the highest antioxidant activity with IC50 value 84.11±0.47 ppm; the quality parameters in this study meet the quality requirements, both specific and nonspecific parameters. Total flavonoid content of the 70% ethanol extract was 2.37±0.02%. The results of the GCMS studies showed the presence of 1,2-benzenedicarboxylic acid, mono (2-ethylhexyl) ester; squalene, methyl palmitate, methyl isopalmitate, n-tetracosanol-1 and 4-isopropyl chalcone. Conclusion: The results indicate that the 70% ethanol extracts of andaliman fruits contains 1,2-benzenedicarboxylic acid, mono (2-ethylhexyl) ester; squalene, methyl palmitate, methyl isopalmitate, n-tetracosanol-1 and 4-isopropyl chalcone have antioxidant activity with IC50 value 51.35 ppm.

The review article summarizes information about seborrheic dermatitis associated with HIV infection. The article presents current literature data about etiology and pathogenesis of seborrheic dermatitis, as well as the features of the clinical manifestations of seborrheic dermatitis associated with HIV infection. This article contains new hypotheses and concepts about combination of these two diseases. The most important role in pathogenesis of seborrheic dermatitis is belong to the fungus Malassazeia , which uses lipids from the skin surface to produce unsaturated and saturated fatty acids. These fatty acids, being left in the individual’s skin, may induce an inflammatory response. At the same time, the total lipid concentration on the skin surface of HIV-positive and HIV-negative patients with seborrheic dermatitis was similar. However, it was reported about significant alterations in the lipid fractions of HIV-positive patients including a reduction in squalene and an increase in cholesterol and in cholesterol esters, which lead to hypercolonization of the skin with yeast-like fungi and their transition in the pathogenic micellar form. The authors present a clinical case, which is demonstrating a severe course of seborrheic dermatitis associated with HIV infection.

Squalene can react with indoor ozone to generate a series of volatile and semi-volatile organic compounds, some of which may be skin or respiratory irritants, causing adverse health effects. Better understanding of the ozone/squalene reaction and product transport characteristics is thus important. In this study, we developed a physical-chemical coupling model to describe the behavior of ozone/squalene reaction products, that is, 6-methyl-5-hepten-2-one (6-MHO) and 4-oxopentanal (4-OPA) in the gas phase and skin, by considering the chemical reaction and physical transport processes (external convection, internal diffusion, and surface uptake). Experiments without intervention were performed in a single-family house in California utilizing time- and space-resolved measurements. The key parameters in the model were extracted from 5 day data and then used to predict the behaviors in some other days. Predictions from the present model can reproduce the concentration profiles of the three compounds (ozone, 6-MHO, and 4-OPA) well (R2 = 0.82-0.89), indicating high accuracy of the model. Exposure analysis shows that the total amount of 6-MHO and 4-OPA entering the blood capillaries in 4 days can reach 14.6 and 30.1 μg, respectively. The contribution of different sinks to ozone removal in the tested realistic indoor environment was also analyzed.

Acne is an inflammatory skin disease of the pilosebaceous unit, involving four essential factors: hyperseborrhoea combined to a modification of sebum composition, colonization by Cutibacterium (C.) acnes, hyperkeratinization and secreted inflammation. Understanding and mimicking compromised skin is essential to further develop appropriate therapeutic solutions. This study aimed to develop new in vitro 3D models mimicking acneic skin, by combining two main factors involved in the physiopathology, namely, altered sebum composition and C. acnes invasion. Normal human keratinocytes were first used to generate reconstructed human epidermis (RHE) that were then left untreated (control) or treated topically with a combination of both peroxidized squalene and C. acnes cultures. Once validated, this model considered relevant to mimic acneic skin, was further improved by using different phylotypes of C. acnes strains specifically isolated from healthy and acneic patients. While both phylotypes IB and II did not significantly alter RHE, C. acnes IA1 strains induce major acneic skin hallmarks such as hyperkeratinization, secreted inflammation and altered barrier function. Interestingly, these results are obtained independently of the origin of IA1 phylotypes (acneic vs. healthy patient), thus suggesting a role of the ecosystem in controlling C. acnes virulence in healthy skin. In conclusion, by combining two major factors involved in the physiopathology of acne, we (1) succeeded to design in vitro 3D models mimicking this skin disorder and (2) highlighted how C. acnes phylotypes can have an impact on epidermal physiology. These relevant models will be suitable for the substantiation of therapeutic molecules dedicated to acne treatment.

The present study was aimed to evaluate the phytochemical contents and hepatocyte protective effects of functional extracts from rice bran of indica and japonica rice cultivars, Dasan 1 and Ilpum, respectively. The highest vitamin E (23.51 mg/g) and phytosterol (390.25 mg/g) content was observed in the unsaponifiable matter (USM) of Dasan 1 cultivar. However, USM of Ilpum showed the highest content of total policosanol and squalene (232.73 mg/g and 99.31 mg/g, respectively). The methanolic extract from the defatted rice bran (MEDR) of Dasan 1 showed the highest total polyphenol content, reducing power, and radical scavenging capacity, while USM of Dasan 1 showed the highest cell viability (81.3%) against oxidative stress in HepG2 cells. USM significantly increased glutathione levels and suppressed the production of reactive oxygen species in hepatocytes compared with methanolic extracts of the rice bran oils and/or MEDR. These results provide useful information on the functional extracts of rice bran from indica and japonica rice cultivars, including their antioxidant properties and cytoprotection in HepG2 cells.

MF59, an oil-in-water nanoemulsion, has been used in licensed seasonal influenza vaccines for many years. Administration of such vaccines by injection is associated with pain and safety issues. Here, we evaluated the potential of administering MF59 via a transcutaneous route with antigen loading (either encapsulated into or mixed with MF59) to intact or microneedle-pretreated skin. In addition to commercial MF59, we also prepared a nanoemulsion to encapsulate hydrophilic antigens by mimicking the formulation and preparation technique of MF59. The nanoemulsion was prepared using a water-in-oil-in-water emulsion method, and was similar to MF59 in composition, particle size, and morphology. Compared with the intact skin group, the microneedle-pretreated group showed significant enhanced antigen penetration. In vivo transcutaneous immunization analysis showed that the MF59-adjuvant influenza vaccine elicited approximately 3–5 times higher hemagglutination inhibition titers than the influenza solution alone in BALB/c mice after microneedle pretreatment. The intact skin group showed negative immune results at the same dose, suggesting that microneedle pretreatment was critical for efficient delivery of antigens, to obtain strong immune responses. Furthermore, the loading method (encapsulation or mixing with the vehicle) did not affect the dermal penetration or transcutaneous immunization of antigens on microneedle-pretreated skin. Moreover, in vitro cellular assays showed that MF59 facilitated the maturation of dendritic cells and enhanced antigen uptake by antigen-presenting cells. In conclusion, the combination of microneedle pretreatment and mixing of MF59 with antigen provides a simple approach to enhance transcutaneous immunization.

Abroma augusta L plant traditionally was used to treat swellings, cuts, sores, and bruises. In the province of Jambi, A. augusta is used in folk medicine to treat wounds. This study aims to isolate the steroid compound from the root of A. augusta L and determine its anti-inflammatory activities. Extraction and fractionation have been done with graded maceration using solvents with different polarities, which are n-hexane, ethyl acetate, and methanol. The separation was performed by column chromatography, followed by preparative thin-layer chromatography. The characterization of the isolate was carried out using UV-Vis spectrophotometry and infrared spectrophotometry, GC-MS. The anti-inflammatory activities of methanol extract and isolate of A. augusta was performed in this study was designed to evaluate the dose-response relationship of the anti-inflammatory activity in rat models of chronic inflammation chromatography to obtain isolate 2.1.1 that characterize and showed maximum absorbance at 265. The result of IR showed the presence of functional groups, -C=C-H, -C=H, -CH, CH3, CH2, and –CO belongs to the steroid compound. The results of the GC-MS show that isolates contain squalene compounds with a value of m/z 410, Isolate and crude extract showed an anti-inflammatory activity that almost approached the positive control of sodium 4-chlorophenolate. It could be concluded that isolate and extract provide good anti-inflammatory activity, that promise for new drug candidate squalene-based A. augusta.

The review gives an insight into amaranth, a very promising crop for the whole world. This crop has a long history dating back to the days of the Aztecs and Incas, for whom it was one of the most important crops, along with corn. However, unlike the latter, amaranth lost its nutritional value after being introduced into Europe. Only in the 20th century, largely thanks to Nikolai Vavilov, amaranth attracted great interest as a food and feed crop. Amaranth is a plant unique in its nutritional properties. It is characterized by a high content of protein saturated with essential amino acids, especially lysine, and a large number of bioactive compounds, such as vitamin C, amaranthine, rutin, carotenoids, etc. Of particular value is grain oil saturated with various lipid compounds: squalene, vitamin E, phytosterols, and fatty acids. These lipid compounds have a number of important properties from the point of view of functional nutrition: as natural antioxidants they bind free radicals, normalize lipid metabolism, and help to decrease blood cholesterol levels. The review focuses on genes that determine the content of the main, valuable biochemical components: squalene, vitamin C, and lysine. The genetic pathways that control the biosynthesis of these components have been studied in detail in various model plant objects. The presence of the complete genomic sequence of Amaranthus hypochondriacus L. makes it possible to identify orthologs of key biosynthetic genes. At the moment, only few genes in amaranth have been identified, including the squalene synthase (SQS) gene, the VTC2 ascorbic acid synthesis gene, and the key genes for lysine synthesis – AK and DHDPS. The article discusses the prospects and trends of marker-assisted selection of this crop as well as the difficulties of its systematization and genotyping, which have to be overcome to successfully solve plant breeding problems.

Physalis angulata is an annual herb which has tremendous medicinal uses. The antioxidant activity of the whole plant extract of Physalis angulata was investigated using DPPH radical scavenging acti...

Identifying drug candidates to target cellular events/signaling that evades von Hippel-Lindau tumor suppressor (VHL) gene interaction is critical for the cure of renal cell carcinoma (RCC). Recently, we characterized a triterpene-squalene derived from marine brown alga. Herein, we investigated the potential of squalene in targeting HIF-signaling and other drivers of RCC progression. Squalene inhibited cell proliferation, induced cell dealth and reverted the cells' metastatic state (migration, clonal expansion) independent of their VHL status. Near-identical inhibition of HIF-1α and HIF-2α and the regulation of downstream targets in VHL wild type and mutant cell lines demonstrated squalene efficacy beyond VHL-HIF interaction. In a rat model of chemically induced RCC, squalene displayed chemopreventive capabilities by substantial reversal of lipid peroxidation, mitochondrial redox regulation, maintaining ∆ψm, inflammation [Akt, nuclear factor κB (NF-κB)], angiogenesis (VEGFα), metastasis [matrix metalloproteinase 2 (MMP-2)], and survival (Bax/Bcl2, cytochrome-c, Casp3). Squalene restored glutathione, glutathione reductase, glutathione-s-transferase, catalase, and superoxide dismutase and stabilized alkaline phosphatase, alkaline transaminase, and aspartate transaminase. The correlation of thiobarbituric acid reactive substance with VEGF/NF-κB and negative association of GSH with Casp3 show that squalene employs reduction in ROS regulation. Cytokinesis-block micronuclei (CBMN) assay in VHLwt/mut cells revealed both direct and bystander effects of squalene with increased micronucleus (MN) frequency. Clastogenicity analysis of rat bone marrow cells demonstrated an anti-clastogenic effect of squalene, with increased polychromatic erythrocytes (PCEs), decreased MNPCE,s and MN normochromatic erythrocytes. Squalene could effectively target HIF signaling that orchestrate RCC evolution. The efficacy of squalene is similar in VHLwt and VHLmut RCC cells, and hence, squalene could serve as a promising drug candidate for an RCC cure beyond VHL status and VHL-HIF interaction dependency. Summary: Squalene derived from marine brown algae displays strong anti-cancer (RCC) activity, functionally targeting HIF-signaling pathway, and affects various cellular process. The significance of squalene effect for RCC is highlighted by its efficiency beyond VHL status, designating itself a promising drug candidate. Graphical abstract.

Carica papaya Linn. is well known for its nutritional and therapeutic properties. Growing, successfully in Egypt environment, we analyzed content of essential minerals, aqueous ethanol extract of leaves for lipoid constituents and main alkaloidal component, examination of in-vivo potential as antioxidant and hepatoprotective, anticancer and antimicrobial activity. Leaves and fruits are good source of micro and macro essential minerals. Squalene, 2-hexadecen-1-ol, β- sitosterol, campesterol and palmitic acid were the major identified lipoid constituents. Carpaine, alkaloid was isolated and identified by different spectroscopic means. 80% Ethanol extract of leaves retained reduced glutathione which were highly compatible to those receiving vitamin E, it retained liver serum levels to which were compatible to the results of those receiving silymarin and demonstrated improvement in deleterious effect induced by CCl4. The extract had moderate effect, while carpaine showed high activity against ovary carcinoma. It had moderate antibacterial activity against Escherichia coli. This plant has highly economic importance.

This study was aimed at evaluating thein vitroeffect of the edible mushroom (EM)Pleurotus eryngiiagainst the eggs and larvae (L3) ofHaemonchus contortus. The evaluation included acetone (AE) and hydroalcoholic (HA) extracts of the following strains: ECS-1138, ECS-1156, ECS-1255, ECS-1258, ECS-1261, ECS-1282, and ECS-1292. The HA extract of the ECS-1255 strain showed the highest effect on mortality rates of L3 (18.83%) at 20 μg/mL. After subjecting this HA extract to a normal phase chromatography column, five fractions were obtained; fraction F5 (100% MeOH) was the most effective against eggs, with hatching inhibition percentages of 88.77 and 91.87% at 20 and 40 mg/mL, respectively. Gas chromatography-mass spectrometry (GC-MS) subjected this fraction to an acetylation reaction to determine the content of the secondary metabolites. The GC-MS analysis showed that the F5 fraction was composed of trehalose CAS: 6138-23-4, polyols (L-iditol CAS: 488-45-9, galactitol CAS: 608-66-2, D-mannitol CAS: 69-65-8, D-glucitol CAS: 50-70-4, and myoinositol CAS: 87-89-8), adipic acid CAS: 124-04-9, stearic acid CAS: 57-11-4, squalene CAS: 111-02-4, andβ-sitosterol CAS: 83-46-5.

Background Metabolomics of Camellia japonica leaf has been studied to identify the terpenoids present in it and their interrelations regarding biosynthesis as most of their pathways are closely situated. Camellia japonica is famous for its anti-inflammatory activity in the field of medicines and ethno-botany. In this research, we intended to study the metabolomics of Camellia japonica leaf by using gas chromatography-mass spectroscopy technique. Results A total of twenty-nine anti-inflammatory compounds, occupying 83.96% of total area, came out in the result. Most of the metabolites are terpenoids leading with triterpenoids like squalene, lupeol, and vitamin E. In this study, the candidate molecules responsible for anti-inflammatory activity were spotted out in the leaf extract and biosynthetic relation or interactions between those components were also established. Conclusion Finding novel anticancer and anti-inflammatory medicinal compounds like lupeol in a large amount in Camellia japonica leaf is the most remarkable outcome of this gas chromatography-mass spectroscopy analysis. Developing probable pathway for biosynthesis of methyl commate B is also noteworthy.

Full-thickness burns pose a major challenge for clinicians to handle because of their restricted self-healing ability. Even though several approaches have been implemented for repairing these burnt skin tissue defects, all of them had unsatisfactory outcomes. Moreover, during recent years, skin tissue engineering techniques have emerged as a promising approach to improve skin tissue regeneration and overcome the shortcomings of the traditional approaches. Although previous literatures report the wound healing effects of the squalene oil, in the current study, for the first time, we developed a squalene-loaded emulgel-based scaffold as a novel approach for potential skin regeneration. This squalene-loaded agar-based emulgel scaffold was fabricated by using physical cross-linking technique using lecithin as an emulsifier. Characterization studies such as X-ray diffraction, Fourier-transform infrared spectroscopy, and field emission scanning electron microscopy revealed the amorphous nature, chemical interactions, and cross-linked capabilities of the developed emulgel scaffold. The squalene-loaded emulgel scaffold showed excellent wound contraction when compared with the agar gel and negative control. In case of the histopathology and recent immunohistochemistry findings, it was clearly evidenced that squalene-loaded emulgel promoted faster rate of the revascularization and macrophage polarization in order to enhance the burn wound healing. Moreover, the findings also revealed that the incorporation of squalene oil into the formulation enhances collagen deposition and accelerates the burnt skin tissue regeneration process. Finally, we conclude that the squalene-loaded emulgel scaffold could be an effective formulation used in the treatment of the burnt skin tissue defects.

Supplemental Digital Content is available in the text., Background: Vaccination against seasonal influenza is recommended for all children with a history of medical conditions placing them at increased risk of influenza-associated complications. The immunogenicity and efficacy of conventional influenza vaccines among young children are suboptimal; one strategy to enhance these is adjuvantation. We present immunogenicity and safety data for an MF59-adjuvanted quadrivalent influenza vaccine (aIIV4) in healthy children and those at a high risk of influenza-associated complications, based on the results of a recently completed phase III study. Methods: Children 6 months to 5 years of age (N = 10,644) were enrolled. The study was conducted across northern hemisphere seasons 2013–2014 and 2014–2015. Subjects received either aIIV4 or a nonadjuvanted comparator influenza vaccine. Antibody responses were assessed by hemagglutination inhibition assay against vaccine and heterologous strains. Long-term antibody persistence was assessed (ClinicalTrials.gov: NCT01964989). Results: aIIV4 induced significantly higher antibody titers than nonadjuvanted vaccine in high-risk subjects. aIIV4 antibody responses were of similar magnitude in high-risk and healthy subjects. Incidence of solicited local and systemic adverse events (AEs) was slightly higher in aIIV4 than nonadjuvanted vaccinees, in both the healthy and high-risk groups. Incidence of unsolicited AEs, serious AEs and AEs of special interest were similar for adjuvanted and nonadjuvanted vaccinees in the healthy and high-risk groups. Conclusion: aIIV4 was more immunogenic than nonadjuvanted vaccine in both the healthy and high-risk study groups. The reactogenicity and safety profiles of aIIV4 and the nonadjuvanted vaccine were acceptable and similar in 6-month- to 5-year-old high-risk and healthy children.

Plant extracts prompting free radical formation causing DNA damage among especially symbiotic microorganisms of Aedes aegypti has not been extensively examined in previous studies. Here, investigated whether: (1) it was possible to reduce the vectorial capacity by eliminating the microbial consortia of Aedes aegypti larvae, (2) the excess formation of free radical could induce damages of genomic DNA and alter the morphological appearance of Aedes aegypti larvae, and (3) which are the probable mechanisms driving the death of mosquitoes that has been treated with phytochemicals. The toxicity of Catunaregam spinosa seed extracts on the microbial community of Aedes aegypti larvae was determined as previously described. The formation of free radicals was confirmed using the ammonium molybdate method. While the GCMS method was used to assess the phytochemical analysis and the DNA lysing potential. The petroleum ether, ethanol, acetone and water extracts of Catunaregam spinosa has exhibited potent toxicity towards Aedes aegypti larvea’s gut bacterial microbiota, including Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Klebsiella pneumonia, and Proteus mirabilis with strong MIC values ranging from 0.07 mg/ml to 5.9 mg/ml. Plant extract induced free radical formations and oxidative damage to DNA. The presence of the bioactive element squalene justifies the insecticidal proprieties of Catunaregam spinosa extract. This study reflects the probable mechanisms underlying the lethal effect of Catunaregam spinosa extract on Aedes aegypti, and it potential as a novel biological vector control approach.

Artocarpus heterophyllus (jackfruit) leaves (JL) are a waste product that is commonly used as livestock feed. Jackfruit leaves have been revealed to possess many medicinal values such as antioxidant and anti-inflammatory properties. In this study, different drying treatments (shade (SD), sun (SN), and oven (OV)) and ethanol/water ratios (E/W) were investigated to evaluate the impact on drying kinetics, color, and antioxidant properties of jackfruit leaves. Results showed that the Newton model was the best fitted mathematical model for the JL drying kinetics. The moisture effective diffusivities ranged from 2.920 × 10-10 to 6.814 × 10-10 m2/s over the temperature range studied. Shade drying was able to preserve the green pigment better than OV and SN drying treatments. Treatment with ethanol/water ratio at 80% and oven-dried (OV80) revealed the highest phenolic content (195.05 ± 1.21 mg gallic acid equivalent (GAE)/g extract weight (EW)), flavonoid content (11.02 ± 0.17 mg artocarpin equivalent (AE)/g EW), and antioxidant activities (90% scavenging activity and reducing power of 1043.84 ± 5.28 µM trolox equivalent (TE)/g EW) compared to SD and SN treatments. The OV80 also possessed the highest artocarpin, squalene, and β-sitosterol contents determined. The OV80 was selected for improving antioxidant and colour stability, and has the potential to be developed into functional biopolymer production.

The present study investigated the phytochemical constituents of Cnidoscolus aconitifolius leaves extracts and its anti-hypercholesterolemia potentials using standard analytical methods. Forty five male albino rats weighing (115-121 g), divided into nine groups of five rats were used. Group I served as the control while the other groups were administered 200, 400, 600 and 800 mg/kg body weight of aqueous and ethanol leaf extracts. GC-MS analysis showed 3,7,1,5-tetramethyl-2-hexadecen-1-ol, farnesyl bromide, β–sitosterol, squalene, β-amyrin, 1-heptatriacotanol, hexadecanoic acid, methyl ester, 2-pentadecanone, 6,10,14-trimethyl- ,n-hexadecanoic acid, 9,12-octadecadienoyl chloride, (Z,Z, δ- tocopherol, Ergosta-5,22-dien-3-ol acetate, (3β,22E)-, 9,10-secocholesta-5,7,10(19)-triene-3,24,25-triol, (3β,5Z,7E)-acetamide, N-methyl-N-[4-(3-hydroxypyrrolidinyl)-2-butynyl]-, 1-gala-I-ido-octose, 10-methyl-E-11-tridecen-1-ol propionate, dodecanoic acid, 2-(acetyloxy)-1-[(acetyloxy)methyl]ethyl ester, 11,14-octadecadienoic acid, methyl ester, cyclopentaneundecanoic acid and methyl ester. Lipid profile showed significant reduction in TC, LDL and TG with increase in HDL in dose dependent ratio. This shows that extracts of this plant could be useful in treatment of coronary heart diseases. Key words: Phytochemicals,hypercholesterolemia, Cnidoscolus aconitifolius, potentials.

Introduction Influenza surveillance in Argentina reported influenza-like illness at a rate of 3500/100,000, a hospitalization rate of 15.5/100,000, and a death rate of 0.32/100,000 annually in adults aged over 65 years. The high burden of disease may be due to a combination of immunosenescence and the suboptimal clinical effectiveness of conventional, non-adjuvanted influenza vaccines in this age group. There is a clinical need for more effective influenza vaccines in this population. This study evaluated the cost-effectiveness of an MF59®-adjuvanted trivalent influenza vaccine (aTIV) in adults aged over 65 years in Argentina compared with the non-adjuvanted trivalent influenza vaccine (TIV) used under the current national vaccination policy. Methods A decision tree cost-effectiveness model was developed to estimate the cost-effectiveness of switching from TIV to aTIV in Argentinian older adults. The model compared cost and health benefits of vaccination in one influenza season from the payer perspective. The main predictions included survival, quality-adjusted survival, and costs. Model inputs were sourced from Argentina or internationally where local data was considered inaccurate. Vaccine efficacy assumptions were extracted from recently published, peer-reviewed scientific literature. Results Switching from TIV to aTIV would result in 170 deaths averted and 1310 incremental quality-adjusted life years (QALYs) gained. The incremental cost-effectiveness ratio per QALY was US $2660.59 from the payer perspective. In all sensitivity analyses, aTIV remained highly cost-effective. The probabilistic sensitivity analyses showed a 95% CI per QALY of US $113.74–7721.67. Conclusion Introducing an adjuvanted influenza vaccine in Argentina is potentially beneficial and cost-effective relative to the currently-used TIV through the reduction of disease burden and utilization of healthcare resources.

Palm fruit as raw material of palm oil is the main commodity of Indonesian agriculture. Palm fatty acid distillate (PFAD) is a by-product of palm oil refinery process in deodorization stage. PFAD contained bioactive compounds such as vitamin E, phytosterols, and squalene. Vitamin E, phytosterols, and squalene have knows for its hypocholesterolemic effect and cardio protector. Bioactive compounds of PFAD can be separated from its fatty acid using saponification reaction. Saponification of PFAD produced unsaponifiable matter (USM) which was rich in bioactive compounds. Food fortification is aimed to enhance the nutrition quality of food for specific reason. The fortificant can be macronutrient or micronutrient. USM of PFAD potentially become food product fortificant which will give hypocholesterolemic effect. This review is discussed about hypocholesterolemic effect of each bioactive compounds in USM of PFAD and the potential of USM as food fortificant espsecially for food with hypocholesterolemic effect.

The immunogenicity benefit of inactivated influenza vaccine (IIV) adjuvanted by squalene over non-adjuvanted aqueous IIV was explored in a meta-analysis involving 49 randomised trials published between 1999 and 2017, and 22,470 eligible persons of all age classes. Most vaccines contained 15 μg viral haemagglutinin per strain. Adjuvanted IIV mostly contained 9.75 mg squalene per dose. Homologous pre- and post-vaccination geometric mean titres (GMTs) of haemagglutination-inhibition (HI) antibody were recorded for 290 single influenza (sub-)type arms. The adjuvant effect was expressed as the ratio of post-vaccination GMTs between squalene-IIV and aqueous IIV (GMTR, 145 estimates). GMTRs > 1.0 favoured squalene-IIV over aqueous IIV. For all influenza (sub-)types, the adjuvant effect proved negatively associated with pre-vaccination GMT and mean age. The adjuvant effect appeared most pronounced in young children (mean age < 2.5 years) showing an average GMTR of 3.7 (95% CI: 2.5 to 5.5). With increasing age, GMTR values gradually decreased towards 1.4 (95% CI: 1.0 to 1.9) in older adults. Heterologous antibody titrations simulating mismatch between vaccine and circulating virus (30 GMTR estimates) again showed a larger adjuvant effect at young age. GMT values and their variances were converted to antibody-predicted protection rates using an evidence-based clinical protection curve. The adjuvant effect was expressed as the protection rate differences, which showed similar age patterns as corresponding GMTR values. However for influenza B, the adjuvant effect lasted longer than for influenza A, possibly due to a generally later influenza B virus exposure. Collectively, this meta-analysis indicates the highest benefit of squalene-IIV over aqueous IIV in young children and decreasing benefit with progressing age. This trend is similar for seasonal influenza (sub-)types and the 2009 pandemic strain, by both homologous and heterologous titration. The impact of pre-seasonal immunity on vaccine effectiveness, and its implications for age-specific vaccination recommendations, are discussed.

Hemigraphis colorata is an indigenous wound healing plant used by various tribes in India since time immortal. This study was aimed to evaluate antibacterial, antioxidant and antielastase effect of hexane extract of Hemigraphis colorata and to identify its bioactive principles. The antioxidant and antibacterial activity of hexane extract were analyzed using in-vitro DPPH scavenging assay and Agar well diffusion method respectively. The antielastase assay was conducted using porcine pancreatic elastase. Biological activity studies revealed that hexane extract of Hemigraphis colorata possess significant antibacterial, antioxidant and antielastase activity. The major phytochemical compound was found to be squalene by GC–MS analysis.

Identifying optimal priming strategies for children2 years could substantially improve the public health benefits of influenza vaccines. Adjuvanted seasonal influenza vaccines were designed to promote a better immune response among young vaccine-naïve children.We systematically reviewed randomized trials to assess hemagglutination inhibition (HAI) antibody response to MF59-adjuvanted inactivated influenza vaccine (aIIV) versus nonadjuvanted IIV among children. We estimated pooled ratios of post-vaccination HAI geometric mean titer (GMT) for aIIV versus IIV and confidence intervals (CIs) using the pooled variances derived from reported CIs.Mean age was 28 months (range, 6-72 months). Children received vaccines with either 7.5 μg (6-35 months) or 15 μg (≥36 months) hemagglutinin of each strain depending on age. Seven of eight trials administered trivalent vaccines and one used quadrivalent vaccine. Pooled post-vaccination GMT ratios against the three influenza vaccine strains were 2.5-3.5 fold higher after 2-dose-aIIV versus 2-dose-IIV among children 6-72 months, and point estimates were higher among children 6-35 months compared with older children. When comparing 1-dose-aIIV to 2-dose-IIV doses, pooled GMT ratios were not significantly different against A/H1N1 (1.0; 95% CI: 0.5-1.8; p = 0.90) and A/H3N2 viruses (1.0; 95% CI: 0.7-1.5; p = 0.81) and were significantly lower against B viruses (0.6; 95% CI: 0.4-0.8; p 0.001) for both age groups. Notably, GMT ratios for vaccine-mismatched heterologous viruses after 2-dose-aIIV compared with 2-dose-IIV were higher against A/H1N1 (2.0; 95% CI: 1.1-3.4), A/H3N2 (2.9; 95% CI: 1.9-4.2), and B-lineage viruses (2.1; 95% CI: 1.8-2.6).Two doses of adjuvanted IIV consistently induced better humoral immune responses against Type A and B influenza viruses compared with nonadjuvanted IIVs in young children, particularly among those 6-35 months. One adjuvanted IIV dose had a similar response to two nonadjuvanted IIV doses against Type A influenza viruses. Longer-term benefits from imprinting and cell-mediated immunity, including trials of clinical efficacy, are gaps that warrant investigation.

Highlights • Transcriptome analysis revealed that PM2.5 significantly up-regulated cholesterol-metabolism-related genes. • PM2.5 significantly increased the epidermal cholesterol level while reduced that of squalene in three-dimensional epidermis tissue model. • Green tea extract was shown to reduce damage from PM2.5 exposure by off-setting the disturbance to epidermal lipid homeostasis., Accumulating evidence suggests that particulate matter (PM2.5), as a major air pollutant, imposes a certain degree of destruction and toxicity to the skin. It particularly impairs the structure and function of the epidermis. To study the impact of PM2.5 on the skin, transcriptome analysis was performed on PM2.5-exposed human primary keratinocytes. Functional annotation analysis demonstrates that PM2.5 significantly up-regulates cholesterol-metabolism-related genes. Via lipid extraction from PM2.5 treated three-dimensional epidermis tissue model (3D-ETM) and subsequent characterization via mass spectrometry, it was confirmed that PM2.5 significantly increases epidermal cholesterol levels in vitro. Conversely, the amount of squalene in 3D-ETM was significantly reduced by PM2.5. Interestingly, neither cholesterol nor squalene showed significant fluctuations in the green tea extract (GTE) treated epidermis tissue model under PM2.5 exposure. This study shows that PM2.5 may cause barrier disorders by increasing cholesterol synthesis, leading to transient accumulation of epidermal cholesterol and decrease of squalene. It was suggested that cholesterol and squalene, which are the key substances affecting skin barrier function, can be used as new biomarkers of skin damage induced by PM2.5. Moreover, it was demonstrated that GTE can reduce damage caused by PM2.5 exposure by not only anti-inflammatory and antioxidant mechanisms, but also by off-setting the disturbance to epidermal lipid homeostasis. This study demonstrates the strong potential of GTE as an active ingredient to be utilized in cosmetic products to effectively reduce the damage PM2.5 induces in skin.