UNASSIGNED: Antibody-mediated protection can depend on mechanisms varying from neutralization to Fc-dependent innate immune-cell recruitment. Adjuvanted vaccine development relies on a holistic understanding of how adjuvants modulate the quantity/titer and quality of the antibody response.
UNASSIGNED: A Phase 2 trial (ClinicalTrials.gov: NCT00805389) evaluated hepatitis B vaccines formulated with licensed adjuvants (AS01B, AS01E, AS03, AS04 or Alum) in antigen-naïve adults. The trial investigated the role of adjuvants in shaping antibody-effector functions, and identified an innate transcriptional response shared by AS01B, AS01E and AS03. We integrated previously reported data on the innate response (gene expression, cytokine/C-reactive protein levels) and on quantitative/qualitative features of the mature antibody response (Fc-related parameters, immunoglobulin titers, avidity). Associations between the innate and humoral parameters were explored using systems vaccinology and a machine-learning framework.
UNASSIGNED: A dichotomy in responses between AS01/AS03 and AS04/Alum (with the former two contributing most to the association with the humoral response) was observed across all timepoints of this longitudinal study. The consistent patterns over time suggested a similarity in the impacts of the two-dose immunization regimen, year-long interval, and non-adjuvanted antigenic challenge given one year later. An innate signature characterized by interferon pathway-related gene expression and secreted interferon-γ-induced protein 10 and C-reactive protein, which was shared by AS01 and AS03, consistently predicted both the qualitative antibody response features and the titers. The signature also predicted from the antibody response quality, the group of adjuvants from which the administered vaccine was derived.
UNASSIGNED: An innate signature induced by AS01- or AS03-adjuvanted vaccines predicts the antibody response magnitude and quality consistently over time.

Medicinal plants Highly aromatic crude materials are utilized for treating warts as an alternative medicine to surgical treatment because they can be permanently removed from the body. Thus, this investigation aimed to extract plant material from Calotropis procera leaves, describe the phytochemical screening, analyze anti-microbial activities, determine the functional groups in FTIR, and identify the chemical compounds in GC-MS. The PH, specific gravity, and viscosity of the crude extracts of Calotropis procera were determined at 4.5, 0.79, and 0.49, respectively. Analyze the solubility of crude extracts; ethanol can dissolve while water does not. Flavonoids, alkaloids, phenols, tannins, and saponins were also present in the phytochemical screening tests of the Calotropis procera extracts, triterpenoids, terpenoids, and steroids were not present in the crude extract. Flavonoids, alkaloids, phenols, tannins, and saponins are the primary phytochemical components found in therapeutic plant material. The Calotropis procera crude extracts analyzed for functional groups by FT-IR contained a hydroxyl group, alkane, carbonyl, aldehyde, ketone, phenols, ester, alcohol, and methylene. The chemical compounds analyzed by GC-MS of Calotropis procera crude material were found to have 22 main compounds. Of 22 compounds, 5 compounds are active ingredients for the applications of medical purposes. The bioactive compounds found in the Calotropis procera plant extract are neophytadiene, hexahydrofarnesyl, lanosterol, 2,4-dimethylbenzo [H]quinolone, and squalene. Those bioactive compounds have anti-bacterial, analgesic, antipyretic, anti-inflammatory, antimicrobial, antioxidant, antiviral, and anti-cancer properties. In an in vitro antimicrobial activity test, the crude extract effectively inhibited more gram-positive bacteria than gram-negative bacteria. This collective reason is why the traditional therapist uses this Calotropis procera plant for the treatment of warts.

The quality of fried products greatly depends on the changes occurring during frying. The purpose of this work was to study the lipid quality changes taking place in selected frozen foods after domestic deep-frying. Conventional, high-linoleic sunflower oil (HLSO) and high-oleic sunflower oil (HOSO) were used, and the frozen foods selected were French fries, croquettes, and nuggets. The foods were fried in domestic fryers under discontinuous conditions. Analyses included fatty acid composition, sterols, tocopherols, squalene, and lipid alteration levels. In all fried foods, the content of lipids increased after frying, which is consistent with previous findings. However, the lipid exchange between the food and the oil greatly depended on the food characteristics. Specifically, the levels of frying oil in the food lipids were about 90, 40, and 58% for French fries, croquettes, and nuggets, respectively. The main results obtained showed that lipid alteration levels considerably decreased and amounts of sterols and tocopherols significantly increased in French fries\' lipids after frying. In both chicken products, croquettes and nuggets, the best quality improvement observed was a significant decrease in cholesterol in food lipids due to the lipid exchange. Overall, frying with HLSO and HOSO improved the quality and nutritional properties of all products tested.

BACKGROUND: It is known that tropospheric ozone (O3) generated from pollutants reacting with UV forms lipid peroxidation products and induces oxidative stress to the skin. With the ever-increasing consumer awareness of the effects pollution has on skin, more testing methods will be needed to evaluate cosmetic ingredients. Recently, others have shown how antioxidants are able to reduce the effects from ozone on skin through in vitro, ex vivo and clinical studies where human subjects place their arms into large stationary chambers.
OBJECTIVE: To develop a small, easy to use ozone exposure module (OEM) that can be used on various sites of the body and to validate this device for use in testing the ability of topical products to mitigate the effects of ozone exposure on the skin.
METHODS: We have produced an OEM which can generate levels of ozone in excess of 1000 ppb and can be set to achieve the equivalent exposure to what is found in polluted environmental conditions. After exposure we used D-squame discs to remove the sebum and analytically quantitate squalene depletion. Squalene, which is very sensitive to ROS, easily oxidizes into early metabolite squalene monohydroperoxide (SQOOH) with ozone exposure.
RESULTS: We were able to show decreases in squalene levels after exposure and protective effects from a topical formulation.
CONCLUSIONS: This generator will be a useful tool for researchers to easily create a small and safe exposure from ozone for clinical testing.
BACKGROUND: On sait que l’ozone troposphérique (O3) générée par les polluants réagissant avec les UV forme des produits de peroxydation lipidique et induit un stress oxydatif pour la peau. Avec la sensibilisation croissante des consommateurs aux effets de la pollution sur la peau, plus de méthodes d’analyse seront nécessaires pour évaluer les ingrédients cosmétiques. Récemment, d’autres méthodes ont montré la capacité des antioxydants à réduire les effets de l’ozone sur la peau grâce à des études in vitro, ex vivo et cliniques où les sujets humains placent leurs bras dans de grandes chambres stationnaires.
OBJECTIVE: Développer un petit module d’exposition à l’ozone (MEO) facile à utiliser qui peut être utilisé sur divers sites corporels afin de valider ce dispositif pour utilisation dans des analyses de capacité des produits topiques à atténuer les effets de l’exposition à l’ozone sur la peau MATÉRIELS ET MÉTHODES: Nous avons produit un MEO qui peut générer des niveaux d’ozone supérieurs à 1 000 ppb et qui peut être réglé pour atteindre l’exposition équivalente aux niveaux présents dans des conditions d’environnement pollué. Après exposition, nous avons utilisé des disques D‐squame pour éliminer le sébum et quantifier analytiquement la déplétion en squalène. Le squalène, qui est très sensible au ROS, s’oxyde facilement en métabolite précoce monohydroperoxyde de squalène (SQOOH) avec exposition à l’ozone RÉSULTATS: Nous avons pu montrer des diminutions des taux de squalène après exposition et les effets protecteurs d’une formulation topique.
CONCLUSIONS: Ce générateur sera un outil utile pour que les chercheurs puissent facilement créer une petite exposition sûre à l’ozone pour les analyses cliniques.

Squalene-based adjuvant compositions that can provide effective induction of specific humoral immune response have been developed. Recombinant receptor-binding domain (RBD) of surface S-protein of SARS-CoV-2 was used to evaluate the properties of the composition. Immunization of mice with the developed squalene-based compositions in combination with RBD allows obtaining high titers of specific antibodies: from 105 to 2×106. The blood sera from immunized mice exhibit neutralizing activity against SARS-CoV-2 Delta variant (B.1.617.2) with a titer up to 1:2000.

CONCLUSIONS: This review ascertains amaranth grains as a potent crop for food security and sustainable food systems by highlighting its agricultural advantages, health benefits and applications in the food, packaging, and brewing industry. The global population surge and rapidly transitioning climatic conditions necessitate the maximization of nutritional crop yield to mitigate malnutrition resulting from food and nutrition insecurity. The modern agricultural practices adopted to maximize the yield of the conventional staple crops are heavily contingent on the depleting natural resources and are contributing extensively to the contamination of these natural resources. Furthermore, these agricultural practices are also causing detrimental effects on the environment like rising emission of greenhouse gasses and increased water footprints. To address these challenges while ensuring sustainable nutrient-rich crop production, it is imperative to utilize underutilized crops like Amaranthus. Amaranth grains are gluten-free pseudo-cereals that are gaining much prominence owing to their abundance in vital nutrients and bio-active components, potential health benefits, resilience to adverse climatic and soil conditions, minimum agricultural input requirements, potential of generating income for small holder farmers as well as various applications across the sustainable value chain. However, due to the limited awareness of these potential benefits of the amaranth grains among the consumers, researchers, and policymakers, they have remained untapped. This review paper enunciates the nutritional composition and potential health benefits of the grains while briefly discussing their various applications in food and beverage industries and accentuating the need to explore further possibilities of valorizing amaranth grains to maximize their utilization along the value chain.

Ursolic acid has gradually attracted much attention due to its unique pharmacological activities and valuable market value in recent years. Currently, ursolic acid is mostly extracted from loquat leaves, but the plant extraction method has low yield and high cost, and chemical synthesis is not readily available, so the biosynthesis method provides a new source for ursolic acid. α-amyrin acts as the main precursor for the synthesis of ursolic acid, and its yield is positively correlated with ursolic acid yield. Oxidosqualene cyclase(OSC) belongs to a multigene family which can catalyze the common precursor 2,3-oxidosqualene to generate different types of triterpene backbones, and plays a decisive role in the synthesis of triterpenoids. However, there are fewer reported key genes catalyzing the synthesis of α-amyrin in medicinal plants, and the yield and proportion of α-amyrin in the catalyzed products have always been a focus of research. In this study, ItOSC2, MdOSC1, AaOSC2 and CrAS, four enzymes capable of catalyzing the production of α-amyrin from 2,3-oxidosqualene, were cloned from Iris tectorum, Malus domestica, Artemisia annua and Catharanthus roseus, subject to sequence alignment and phylogenetic tree analyses, and transformed into Saccharomyces cerevisiae as plasmids. After 7 days of fermentation, the yield and proportions of α-amyrin, β-amyrin and ergosterol were measured. Finally, AaOSC2 with the best ability to catalyze the generation of α-amyrin was filtered out, providing a key gene element for the later construction of engineered yeast strains with high production of α-amyrin and ursolic acid.

Feline coronavirus (FCoV) infection is a leading cause of death in cats. In this study, we produced FCoV-I virus-like particles (VLPs) containing E, M, N, and S proteins using a baculovirus expression system and mixed VLPs with the adjuvants MF59 and CpG 55.2 to prepare an VLP/MF59/CpG vaccine. After immunization of mice with the vaccine, IgG specific antibodies titers against S and N proteins increased to 1:12,800, and IFN-γ+ and IL-4+ splenocytes were significantly increased. Following immunization of FCoV-negative cats, the S protein antibodies in immunized cats (5/5) increased significantly, with a peak of 1:12,800. Notably, after booster vaccination in FCoV-positive cats, a significant reduction in viral load was observed in the feces of partial cats (4/5), and the FCoV-I negative conversion was found in two immunized cats (2/5). Therefore, the VLP/MF59/CpG vaccine is a promising candidate vaccine to prevent the FCoV infection.

This study explores the potential of a nanomedicine approach, using Leu-enkephalin-squalene nanoparticles (LENK-SQ NPs) for managing long-lasting pain. It was observed that the nanomedicine significantly improved the pharmacological efficacy of the Leu-enkephalin, a fast metabolized neuropeptide, in a rat model of acute inflammatory pain, providing local analgesic effect, while minimizing potential systemic side effects by circumventing central nervous system. The LENK-SQ NPs were tested in a rat model of postoperative pain (Brennan\'s rodent plantar incision model) using continuous infusion via Alzet® pump, with an additional bolus injection. The analgesic activity was assessed through stimulus-evoked methods, such as the von Frey and Hargreaves tests. Both mechanical and thermal hyperalgesia were significantly reduced at days 2 and 3 post-incision. An additional pharmacokinetic study was conducted, showing that LENK-SQ NPs allowed a sustained circulation of the neuropeptide under its prodrug form. On the other hand, the biodistribution of fluorescently labelled LENK-SQ NPs revealed their selective accumulation in the incised paw within the first hour post administration, followed by a disassembly of the NPs, starting 24 h later. The study proposes the following multi-step mechanism for the anti-nociceptive pharmacological activity of LENK-SQ NPs: (i) protection of the neuropeptide from metabolization into the bloodstream, (ii) targeted accumulation of the nanoparticles within the incised painful tissue and (iii) gradual release of LENK at the onset of the inflammatory process, leading to the observed analgesic activity.

OBJECTIVE: This study evaluated relative vaccine effectiveness (rVE) of MF59-adjuvanted trivalent inactivated influenza vaccine (aTIV) vs high-dose trivalent inactivated influenza vaccine (HD-TIV) for prevention of test-confirmed influenza emergency department visits and/or inpatient admissions (\"ED/IP\") and for IP admissions alone pooled across the 2017-2020 influenza seasons. Exploratory individual season analyses were also performed.
METHODS: This retrospective test-negative design study included United States (US) adults age ≥65 years vaccinated with aTIV or HD-TIV who presented to an ED or IP setting with acute respiratory or febrile illness during the 2017-2020 influenza seasons. Test-positive cases and test-negative controls were grouped by vaccine received. The rVE of aTIV vs HD-TIV was evaluated using a combination of inverse probability of treatment weighting and logistic regression to adjust for potential confounders.
RESULTS: Pooled analyses over the three seasons found no significant differences in the rVE of aTIV vs HD-TIV for prevention of test-confirmed influenza ED/IP (-2.5% [-19.6, 12.2]) visits and admissions or IP admissions alone (-1.6% [-22.5, 15.7]). The exploratory individual season analyses also showed no significant differences.
CONCLUSIONS: Evidence from the 2017-2020 influenza seasons indicates aTIV and HD-TIV are comparable for prevention of test-confirmed influenza ED/IP visits in US adults age ≥65 years.