Linalool: Therapeutic Indication And Their Multifaceted Biomedical Applications.

This comprehensive review endeavors to illuminate the nuanced facets of linalool, a prominent monoterpene found abundantly in essential oils, constituting a massive portion of their composition. The biomedical relevance of linalool is a key focus, highlighting its therapeutic attributes observed through anti-nociceptive effects, anxiolytic properties, and behavioral modulation in individuals affected by dementia. These findings underscore the compound's potential application in biomedical applications. This review further explores contemporary formulations, delineating the adaptability of linalool in nano-emulsions, microemulsions, bio-capsules, and various topical formulations, including topical gels and lotions. This review covers published and granted patents between 2018-2024 and sheds light on the evolving landscape of linalool applications, revealing advancements in dermatological, anti-inflammatory, and antimicrobial domains.

Innovative Alkanediol-Based Eutectic Solvents for Extracting/Pre-Formulating Dermatologically Valuable Free Fatty Acids from Spirulina and Porphyridium Cakes.

The growing demand for phycobiliproteins from microalgae generates a significant volume of by-products, such as extraction cakes. These cakes are enriched with products of interest for the cosmetics market, namely free fatty acids, particularly polyunsaturated (PUFA). In this work, two cakes, one of spirulina and one of Porphyridium cruentum, were valorized using innovative natural hydrophobic deep eutectic solvents (NaDES) based on alkanediols. The most promising NaDES, as determined by physicochemical properties and screening, are mixtures of alkanediols and fatty acids. These include the mixtures of 1,3-propanediol and octanoic acid (1:5, mol/mol) and 1,3-propanediol and octanoic and decanoic acid (1:3:1, mol/mol). Two extractive processes were implemented: ultrasound-assisted extraction and an innovative mechanical process involving dual asymmetric centrifugation. The second process resulted in the production of extracts significantly enriched in PUFA, ranging from 65 to 220 mg/g dry matter with the two cakes. The extracts and NaDES demonstrated good safety with respect to epidermal keratinocyte viability (>80% at 200 µg/mL). The study of their impact on commensal and pathogenic cutaneous bacteria demonstrated significant effects on the viability of Staphylococcus aureus and Staphylococcus epidermidis (>50% decrease at 200 µg/mL) while preserving Corynebacterium xerosis and Cutibacterium acnes. These results highlight the potential of valorizing these co-products using alkanediol-based NaDES, in a strategy combining an active vector (NaDES) and a growth regulator extract, for the management of cutaneous dysbiosis involving staphylococci.

Efficacy and safety of deucravacitinib for the management of psoriasis: a drug safety evaluation.

INTRODUCTION: Nowadays, despite the wide availability of biological drugs and apremilast for psoriasis management, there is always a need for new therapies to customize the therapeutic approach on the basis of the patient's clinical features and comorbidities, especially in order to achieve a prolonged therapeutic response. Thus, new treatment strategies are required to offer patients a personalized approach. In this scenario, major knowledge on psoriasis pathogenesis led to the development of deucravacitinib, an orally administered selective TYK2 inhibitor. AREAS COVERED: The aim of this manuscript is to review the current literature on the effectiveness and safety of deucravacitinib in psoriasis to offer readers a wide perspective. The current English literature was analyzed using the PubMed, Google Scholar, Embase, Cochrane Skin, and clinicaltrials.gov databases, selecting the most relevant manuscripts. EXPERT OPINION: Deucravacitinib appears to be an innovative weapon for the management of moderate to severe psoriasis. Despite its efficacy and safety profiles have been revealed by RCTs, real-life data are still scant. Certainly, deucravacitinib broadens the range of therapeutic alternatives for psoriasis patients, thus enhancing the holistic and personalized approaches required for the treatment of this disease.

Drug Survival of IL-17 and IL-23 Inhibitors for Psoriasis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: The most recently approved biologics for moderate-to-severe psoriasis are the interleukin (IL)-17 and IL-23 inhibitors. Drug survival is a frequently used outcome to assess drug performance in practice. An overview of the available drug survival studies regarding IL-17 and IL-23 inhibitors is lacking. Therefore, our objective was to assess the drug survival of IL-17 and IL-23 inhibitors for psoriasis. METHODS: A search of PubMed, Embase, Cochrane Library and Web of Science was conducted (last search 27 December, 2023). Inclusion criteria were (1) cohort study; (2) patients aged ≥ 18 years with plaque psoriasis; and (3) evaluation of drug survival of at least one of the IL-17 and IL-23 inhibitors. Exclusion criteria were: primary focus on patients with psoriatic arthritis, fewer than ten study subjects and another language than English. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Survival probabilities at monthly intervals were extracted from Kaplan-Meier curves using a semi-automated tool. Data were pooled using a non-parametric random-effects model to retrieve distribution-free summary survival curves. Summary drug survival curves were constructed per biologic for different discontinuation reasons: overall, ineffectiveness and adverse events, and split for the effect modifier biologic naivety. Results were analysed separately for registry/electronic health record data and for pharmacy/claims data. RESULTS: A total of 69 studies aggregating drug survival outcomes of 48,704 patients on secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, and tildrakizumab were included. Summary drug survival estimates of registry/electronic health record studies for overall, ineffectiveness and adverse event related drug survival were high (all point estimates ≥ 0.8 at year 1) for included biologics, with highest estimates for guselkumab and risankizumab. All estimates for drug survival were higher in biologic naive than in experienced patients. Estimates of pharmacy/claims databases were substantially lower than estimates from the primary analyses based on registry/electronic health record data. CONCLUSIONS: This meta-analysis showed that the investigated IL-17 and IL-23 inhibitors had high drug survival rates, with highest rates for guselkumab and risankizumab drug survival. We showed that effect modifiers such as biologic naivety, and the source of data used (registry/electronic health record data vs pharmacy/claims databases) is relevant when interpreting drug survival studies.

Clinical pharmacokinetics and pharmacodynamics of oral systemic nonbiologic therapies for psoriasis patients.

INTRODUCTION: Psoriasis is a chronic inflammatory immune condition. Treatments for psoriasis vary with disease severity, ranging from topicals to systemic biologic agents. The pharmacokinetic (PK) and pharmacodynamic (PD) properties of these therapies establish drug efficacy, toxicity, and optimal dosing to ensure therapeutic drug levels are sustained and adverse effects are minimized. AREAS COVERED: A literature search was performed on PubMed, Google Scholar, and Ovid MEDLINE for PK and PD, efficacy, and safety data regarding oral systemic nonbiologic therapies utilized for moderate-to-severe plaque psoriasis. The findings were organized into sections for each drug: oral acitretin, methotrexate, cyclosporine, apremilast, tofacitinib, and deucravacitinib. EXPERT OPINION: Some psoriasis patients may not respond to initial therapy. Ongoing research is evaluating genetic polymorphisms that may predict an improved response to specific medications. However, financial and insurance barriers, as well as limited genetic polymorphisms correlated with treatment response, may restrict the implementation of genetic testing necessary to personalize treatments. How well psoriasis patients adhere to treatment may contribute greatly to variation in response. Therapeutic drug monitoring may help patients adhere to treatment, improve clinical response, and sustain disease control.

Clinical pharmacokinetics and pharmacodynamics of topical non-biological therapies for psoriasis patients.

INTRODUCTION: Psoriasis is a chronic inflammatory cutaneous disease that causes patients psychosocial distress. Topical therapies are utilized for mild-to-moderate disease and for more severe disease in conjunction with systemic therapies. Topical corticosteroids are a cornerstone of treatment for psoriasis, but long-term use can cause stria and cutaneous atrophy and as well as systemic side effects such as topical steroid withdrawal. Non-steroidal topical therapies tend to be safer than topical corticosteroids for long-term use. AREAS COVERED: We conducted a literature review on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of topical therapies for psoriasis. We discuss how the PK and PD characteristics of these therapies inform clinicians on efficacy and toxicity when prescribing for patients. EXPERT OPINION: Topical corticosteroids, used intermittently, are very safe and effective. Long-term, continuous use of topical corticosteroids can cause systemic side effects. Several generic and newly approved non-steroidal options are available, but no head-to-head studies compare the effectiveness of the generics (vitamin D analogs, tacrolimus, pimecrolimus) against the newer therapies (roflumilast, tapinarof). Patients often do not respond to topical therapies due to poor adherence to treatment regimens. For patients resistant to topical treatment, phototherapy or systemic therapy may be an option.

Brilaroxazine lipogel displays antipsoriatic activity in imiquimod-induced mouse model.

BACKGROUND: Dopamine (D) and serotonin (5-HT) pathways contribute to psoriasis pathobiology. Disruptions incite increased inflammatory mediators, keratinocyte activation and deterioration, and worsening symptoms. Brilaroxazine (RP5063), which displays potent high binding affinity to D2/3/4 and 5-HT1A/2A/2B/7 receptors and a moderate affinity to serotonin transporter (SERT), may affect the underlying psoriasis pathology. METHODS: An imiquimod-induced psoriatic mouse model (BALB/c) evaluated brilaroxazine's activity in a topical liposomal-aqueous gel (Lipogel) formulation. Two of the three groups (n = 6 per) underwent induction with 5% imiquimod, and one group received topical brilaroxazine Lipogel (Days 1-11). Assessments included (1) Psoriasis Area and Severity Index (PASI) scores (Days 1-12), skin histology for Baker score based on H&E stained tissue (Day 12), and serum blood collection for serum cytokine analysis (Day 12). One-way ANOVA followed by post hoc Dunnett's t-test evaluated significance (p < 0.05). RESULTS: Imiquimod-induced animal Baker scores were higher versus Sham non-induced control's results (p < 0.001). Brilaroxazine Lipogel had significantly (p = 0.003) lower Baker scores versus the induced Psoriasis group. Brilaroxazine PASI scores were lower (p = 0.03) versus the induced Psoriasis group (Days 3-12), with the greatest effect in the last 3 days. The induced Psoriasis group showed higher Ki-67 and TGF-ß levels versus non-induced Sham controls (p = 0.001). The brilaroxazine Lipogel group displayed lower levels of these cytokines versus the induced Psoriasis group, Ki-67 (p = 0.001) and TGF-ß (p = 0.008), and no difference in TNF-α levels versus Sham non-induced controls. CONCLUSION: Brilaroxazine Lipogel displayed significant activity in imiquimod-induced psoriatic animals, offering a novel therapeutic strategy.

Targeting the NLRP3 inflammasome in psoriasis.

The NLRP3 inflammasome, a complex consisting of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3, has emerged as a critical mediator of pathological inflammation and a significant therapeutic target for various inflammatory diseases. Psoriasis, a chronic inflammatory skin condition without a definitive cure, has shown promising results in animal models through the inhibition of the NLRP3 inflammasome. This review aims to explore the development of the NLRP3 inflammasome in psoriasis and the molecular mechanisms responsible for its inhibition by natural products and small molecules currently being developed for psoriasis treatment. Furthermore, we are examining clinical trials using agents that block the NLRP3 pathway for the treatment of psoriasis. This study is timely to provide a new perspective on managing psoriasis.

Combinational antimicrobial activity of biogenic TiO2 NP/ZnO NPs nanoantibiotics and amoxicillin-clavulanic acid against MDR-pathogens.

The development of effective strategies against multidrug-resistant (MDR) pathogens is an urgent need in modern medicine. Nanoantibiotics (nABs) offer a new hope in countering the surge of MDR-pathogens. The aim of the current study was to evaluate the antibacterial activity of two attractive nABs, TiO2 NPs and ZnO NPs, and their performance in improving the antimicrobial activity of defined antibiotics (amoxicillin-clavulanic acid, amox-clav) against MDR-pathogens. The nABs were synthesized using a green method. The physicochemical characteristics of the synthesized nanoparticles were determined using standard methods. The results showed the formation of pure anatase TiO2 NPs and hexagonal ZnO NPs with an average particle size of 38.65 nm and 57.87 nm, respectively. The values of zeta potential indicated the high stability of the samples. At 8 mg/mL, both nABs exhibited 100 % antioxidant activity, while ZnO showed significantly higher activity at lower concentrations. The antibiofilm assay showed that both nABs could inhibit the formation of biofilms of Acinetobacter baumannii 80 and Escherichia coli 27G (MDR-isolates). However, ZnO NPs showed superior antibiofilm activity (100 %) against E. coli 27G. The MIC values were determined to be 8 (1), 2 (2), and 4 (4) mg/mL for amox-clav, TiO2 NPs, and ZnO NPs against A. baumannii 80 (E. coli 27G), respectively. The results showed that both nABs had synergistically enhanced antibacterial performance in combination with amox-clav. Specifically, an 8-fold reduction in MIC values of antibiotics was observed when they were combined with nABs. These findings highlight the potential of TiO2 NPs and ZnO NPs as effective nanoantibiotics against MDR-pathogens. The synergistic effect observed when combining nABs with antibiotics suggests a promising approach for combating antibiotic resistance. Further research and development in this area could lead to the development of more effective treatment strategies against MDR infections.

Role of Apoptotic-targeted Phytoconstitutent-loaded Antipsoriatic Nanobiocomposites.

Psoriasis is an inflammatory and proliferative autoimmune dermatological disorder. It is a skin ailment that is defined by particular, drab-red or peach-pink stiff areas with silvery scales patches. Other typical characteristics include the proliferation of epidermal layer, aberrant keratinization, hyperkeratosis, increased micro capillary vascularization, and infiltration of inflammatory mediator loaded cells. Conventional pharmacotherapies currently available can only provide minor advantages. Nanomedicines based on nanotechnology can potentially improve the efficacy and safety of psoriasis medications. Apoptosis plays an important pathogenetic role in many chronic inflammatory diseases, including those of dermatological interest, in particular, regarding psoriasis. In this regard, treatments with antioxidant properties could be appropriate therapeutic options. We reviewed the available studies on the efficacy of antiapoptotic therapies in psoriasis. We'll look at phytochemicals in this review, which are natural components found in plants with antiapoptotic activity that are frequently used to treat psoriasis. For improved topical treatment, we also take into consideration the advantages of loading phytoconstituents as medicines into lipid based nanocarriers. The utilization of herbal nanomedicines in psoriasis, as well as nano delivery carrier system for phytoconstituents with improved therapeutic profiles and decreased toxicity, are the subjects of this review. The study's purpose is to find more effective herbal nanomedicines for treating psoriasis. In the treatment of psoriasis, phytoconstituents that have shown antipsoriatic potential in recent years, as well as phytoconstituents loaded based nanomedicines, have a lot of promising roles to be explored. Furthermore, very few patents have been found in the field of nanotechnology utilizing lipid-based nanocarrier system for the treatment of psoriasis. Therefore, this review greatly compels the researcher to validate the process development of lipid-based drug delivery system for the patentability of the product. This should be in a view of shifting in the applicability of the drug delivery system for general public health as a potential treatment option in psoriasis.

Transparent silicone-free shampoo containing proteins with strong hair conditioning properties.

OBJECTIVE: With the constant upgrading of healthcare concepts, silicone-free hair products have attracted more attention among consumers. In the present study, transparent silicone-free shampoo containing proteins was successfully fabricated by mixing mild non-sulphate surfactants, compound cationic conditioners, natural silicone oil substitutes, protein conditioners, thickeners, and other auxiliary ingredients. The effects of the type of surfactants, hair conditioners and thickeners, the type and content of proteins, and the mass ratio of compound proteins on the hair foaming performance, hair grooming performance, and penetration performance were investigated. METHODS: The basic formulation framework for transparent silicone-free shampoo was established at first. Then, various hydrolyzed proteins were further added to the basic formulation in the form of single use or compound use to prepare transparent silicone-free shampoo containing different proteins. The morphology of hair samples and penetration of protein in hair were evaluated with a scanning electron microscope and laser confocal fluorescence microscopy, respectively. And the hair grooming performance was also determined by a dynamic combing tester. RESULTS: The compound proteins of Croquat WKP PE-LQ-WD and Gluadin® Kera-PLM with mass ratios of 1:9 and 1:1 at 2 wt% total protein content added to the silicone-free shampoo brought a higher contact angle and a lower frictional coefficient than commercial silicone-free shampoo without proteins. In addition, the compound proteins also have the dual effect of adsorbing the hair surface and penetrating deep into the interior of the hair. CONCLUSION: The combination of cationic modified hydrolyzed protein (e.g., Croquat WKP PE-LQ-WD) and hydrolyzed protein with low molecular weight (e.g., Gluadin® Kera-P LM) at an appropriate mass ratio exhibited a strong synergistic effect on hair conditioning properties. It could provide a significant reference for developing silicone-free hair products with more benefits.

OBJECTIF: Avec l'amélioration constante des concepts de soins de santé, les produits capillaires sans silicone ont attiré l'attention des consommateurs. Dans la présente étude, un shampooing transparent sans silicone contenant des protéines a été fabriqué avec succès en mélangeant des tensioactifs doux sans sulfate, des conditionneurs cationiques composés, des substituts naturels de l'huile de silicone, des conditionneurs protéiques, des épaississants et d'autres ingrédients auxiliaires. On a étudié les effets du type de tensioactifs, de conditionneurs pour les cheveux et d'épaississants, du type et de la teneur en protéines et du rapport massique des protéines composées sur les performances de moussage des cheveux, du nettoyage des cheveux et de la pénétration. MÉTHODES: le cadre de formulation de base pour le shampooing transparent sans silicone a d'abord été établi. Ensuite, diverses protéines hydrolysées ont été ajoutées à la formulation de base sous forme d'utilisation unique ou d'utilisation de composés pour préparer un shampooing transparent sans silicone contenant différentes protéines. La morphologie des échantillons de cheveux et la pénétration des protéines dans les cheveux ont été évaluées à l'aide d'un microscope électronique a balayage et d'une microscopie confocale laser à fluorescence, respectivement. Les performances de nettoyage des cheveux ont également été déterminées par un testeur de peignage dynamique. RÉSULTATS: les protéines composées de Croquat WKP PE-LQ-WD et de GluadinR Kera-PLM avec des rapports massiques de 1:9 et 1:1 à 2 % en poids de teneur en protéines totales ajoutées au shampooing sans silicone ont un angle de contact plus élevé et un coefficient de frottement plus faible que le shampooing sans silicone commercial sans protéines. En outre, les protéines composées ont également doublé l'effet d'adsorption à la surface des cheveux et de pénétration à l'intérieur des cheveux. CONCLUSION: la combinaison de protéines hydrolysées modifiées cationiques (par exemple, Croquat WKP PE-LQ-WD) et de protéines hydrolysées de faible poids moléculaire (par exemple, GluadinR Kera-P LM) avec un rapport massique approprié a montré un fort effet synergique sur les propriétés de conditionnement des cheveux. Il pourrait fournir une référence significative pour le développement de produits capillaires sans silicone avec plus d'avantages.

Effects of a lotion containing probiotic ferment lysate as the main functional ingredient on enhancing skin barrier: a randomized, self-control study.

There is an emergent need to develop functional cosmetic ingredients for the topical management of skin barrier function. This study aimed to investigate the efficacy of a lotion containing fermented lysates VHProbi® Mix R for enhancing the skin barrier. In vitro studies demonstrated that fermented cultures of both Lacticaseibacillus rhamnosus VHProbi® E06 (E06) and L. paracasei VHProbi® E12 (E12) had antioxidant capacity, showing promising scavenging capability for 2,2-diphenyl-1-picryl-hydrazyl. The antioxidant capacity of these strains was also demonstrated in the model of Caenorhabditis elegans. In addition, the fermented lysates of both E06 and E12 enhanced the proliferation of HaCaT cells and ameliorated the toxicity induced by Staphylococcus aureus ATCC 25923, hydrogen peroxide, and ultraviolet B radiation in the HaCaT cell models, which simulated the irritants that facial sensitive skin is exposed to. Subsequently, the ingredient VHProbi® Mix R was formulated using four kinds of fermented lysates: E06, E12, Lactiplantibacillus plantarum VHProbi® E15, and Lactobacillus helveticus VHProbi® Y21. A clinical study was conducted to investigate whether a lotion containing VHProbi® Mix R would be beneficial for people to enhance skin barrier. The participants were asked to use the investigational product for 30 days. Several indicators, including transepidermal water loss (TEWL), skin moisturization, and redness were measured at day 0 and day 30 using VISIA®-CR and CK®-MPA systems. Meanwhile, the burden of sensitive skin (BoSS) and self-assessment questionnaires were performed at baseline and endpoint of this study. The study data showed that at day 30, there was a significant decrease in TEWL (P < 0.01), redness measured by CK®-MPA (P < 0.01), and redness profile measured by VISIA®-CR compared with the baseline measurements. Skin moisturization had significantly increased after treatment with the lotion for 30 days. BoSS and self-assessment questionnaires also substantiated that the participants felt a markedly positive change in their sensitive skin. Hence, we hypothesize that applying the topical functional VHProbi® Mix R could confer effective benefits for people with sensitive skin and this represents a promising intervention for enhancing skin barrier.

Antiviral Evaluation of New Synthetic Bioconjugates Based on GA-Hecate: A New Class of Antivirals Targeting Different Steps of Zika Virus Replication.

Re-emerging arboviruses represent a serious health problem due to their rapid vector-mediated spread, mainly in urban tropical areas. The 2013-2015 Zika virus (ZIKV) outbreak in South and Central America has been associated with cases of microcephaly in newborns and Guillain-Barret syndrome. We previously showed that the conjugate gallic acid-Hecate (GA-FALALKALKKALKKLKKALKKAL-CONH2)-is an efficient inhibitor of the hepatitis C virus. Here, we show that the Hecate peptide is degraded in human blood serum into three major metabolites. These metabolites conjugated with gallic acid were synthesized and their effect on ZIKV replication in cultured cells was evaluated. The GA-metabolite 5 (GA-FALALKALKKALKKL-COOH) was the most efficient in inhibiting two ZIKV strains of African and Asian lineage at the stage of both virus entry (virucidal and protective) and replication (post-entry). We also demonstrate that GA-metabolite 5 does not affect cell growth after 7 days of continuous treatment. Thus, this study identifies a new synthetic antiviral compound targeting different steps of ZIKV replication in vitro and with the potential for broad reactivity against other flaviviruses. Our work highlights a promising strategy for the development of new antivirals based on peptide metabolism and bioconjugation.

Toxicological evaluation of a nonlethal riot control combinational formulation upon dermal application using animal models.

Numerous adverse effects on human health have been reported in epidemiological studies of oleoresin capsicum (OC) and other riot control agents (RCAs). Importantly, the daunting risk of such RCAs can be neutralized by optimizing the desired concentration of such agents for mob dispersal. Hence, a nonlethal riot control combinational formulation (NCF) was prepared for dispersing rioters without imparting fatal outcomes. However, for desired utilization of NCF, it is essential to recognize its extent of potential toxicity. Therefore, the current investigation evaluated the dermal toxicity of NCF using experimental animals in compliance with the OECD guidelines. Additionally, few essential metal ions were analyzed and found non -significantly different in the test rats as compared to control rats. Moreover, abnormal dermal morphology and lesions ultrastructural tissue defects were not noticed as evinced by different studies like ultrasonography, histology, and scanning electron microscopy (SEM) respectively. Further, Doppler ultrasonography exhibited non-significantly different blood flow velocity in both groups, whereas miles test demonstrated a significantly increased Evans blue concentration in test rats compared to the control rats, which might be due to an initial increase in blood flow via an instant action of the NCF at the cutaneous sensory nerve endings. However, our results demonstrated NCF can produce initial skin irritating and sensitizing effects in guinea pigs and rabbits without the antecedence of acute toxicity (≤2000 mg/kg) in Wistar rats.

Topical application of aerial portion of Acalypha indica Linn ameliorates psoriasis in rodents: Evidences from in vivo and in silico studies.

ETHANOPHARMACOLOGICAL RELEVANCE: Acalypha indica Linn. is a weed, used traditionally for different skin diseases such as eczema and dermatitis in various parts of India. There are no previous in vivo studies reported on the antipsoriatic potential of this medicinal plant. AIM: The aim of this study was to investigate antipsoriatic activity of coconut oil dispersion of aerial portion of Acalypha indica Linn. Few lipid-soluble phytoconstituents of this plant were subjected to molecular docking studies on different targets to determine phytoconstituent responsible for antipsoriatic activity. METHODS: Virgin coconut oil dispersion of aerial portion of the plant was prepared by mixing three parts of coconut oil and one part of powdered aerial portion. The acute dermal toxicity was determined according to OECD guidelines. Mouse tail model was used to evaluate the antipsoriatic activity. Molecular docking of phytoconstituents was carried out using Biovia Discovery Studio. RESULTS: In acute dermal toxicity study,the coconut oil dispersion was found to be safe up to the dose of 20000 mg/kg. The dispersion exhibited significant antipsoriatic activity (p < 0.01) at the dose of 250 mg/kg; at 500 mg/kg dose, the activity was similar that of 250 mg/kg dose. In the docking study of the phytoconstituents, 2-methyl anthraquinone was found to be responsible for antipsoriatic activity. CONCLUSION: This study provides new evidence of Acalypha indica Linn as antipsoriatic plant and justifies its traditional use. Computational studies also endorse the results obtained via acute dermal toxicity study and mouse tail model for evaluation of antipsoriatic potential.

Five-Membered Heterocyclic Sulfonamides as Carbonic Anhydrase Inhibitors.

The development of heterocyclic derivatives has progressed considerably over the past decades, and many new carbonic anhydrase inhibitors (CAIs) fall into this field. In particular, five-membered heterocyclic sulfonamides have been generally shown to be more effective inhibitors compared to six-membered rings ones. Despite the importance of oxygen and nitrogen five-membered heterocyclic aromatic rings in medicinal chemistry, the installation of sulfonamide moiety on such heterocycles has not received much attention. On the other hand, 1,3,4-thiadiazole/thiadiazoline ring-bearing sulfonamides are the scaffolds which have been widely used in a variety of pharmaceutically important CAIs such as acetazolamide, metazolamide and their many derivatives obtained by using the tail approach. Here, we reviewed the field focusing on the diverse biological activities of these CAIs, such as antiglaucoma, antiepileptic, antitumor and antiinfective properties. This review highlights developments involving five-membered heterocyclic sulfonamides over the last years, with a focus on their pharmacological/clinical applications.

IL17A Blockade with Ixekizumab Suppresses MuvB Signaling in Clinical Psoriasis.

Unbiased informatics approaches have the potential to generate insights into uncharacterized signaling pathways in human disease. In this study, we generated longitudinal transcriptomic profiles of plaque psoriasis lesions from patients enrolled in a clinical trial of the anti-IL17A antibody ixekizumab (IXE). This dataset was then computed against a curated matrix of over 700 million data points derived from published psoriasis and signaling node perturbation transcriptomic and chromatin immunoprecipitation-sequencing datasets. We observed substantive enrichment within both psoriasis-induced and IXE-repressed gene sets of transcriptional targets of members of the MuvB complex, a master regulator of the mitotic cell cycle. These gene sets were similarly enriched for pathways involved in the regulation of the G2/M transition of the cell cycle. Moreover, transcriptional targets for MuvB nodes were strongly enriched within IXE-repressed genes whose expression levels correlated strongly with the extent and severity of the psoriatic disease. In models of human keratinocyte proliferation, genes encoding MuvB nodes were transcriptionally repressed by IXE, and depletion of MuvB nodes reduced cell proliferation. Finally, we made the expression and regulatory networks that supported this study available as a freely accessible, cloud-based hypothesis generation platform. Our study positions inhibition of MuvB signaling as an important determinant of the therapeutic impact of IXE in psoriasis.

Reduction of wrinkles: From a computational hypothesis to a clinical, instrumental, and biological proof.

BACKGROUND: Facial wrinkles are clear markers of the aging process, being chronological, photo-induced, or reflecting repetitive facial expressions. The aim of this study is to provide new insights into the biophysical and biological mechanisms involved in the formation, prevention, or elimination of the expression wrinkles. MATERIALS AND METHODS: We use a computational model to get a better understanding of the wrinkle mechanical behavior and evolution after skin softening and suggesting a possible antiaging mechanism. Then, we provide a clinical demonstration of the anti-wrinkle effect of a long-term application of a 20% glycerol in a moisturizer formula (GBM) versus its vehicle on crow's feet. Skin hydration, elasticity, and wrinkles visibility were evaluated by a combination of clinical and instrumental in vivo data, inverse finite element analysis, and proteomic data. RESULTS: The computational model shows a predominantly compressive stress beneath the wrinkle and its significant decrease by the softening of stratum corneum. The associated clinical study confirmed a significant increase of skin hydration and elasticity as well as a decrease of wrinkle visibility after 2 and 4 months as application for both formulas; this effect being stronger for GBM. A softening effect on stratum corneum and dermis was also observed for the GBM. Furthermore, proteomic data revealed an effect of upregulation of four proteins associated with desquamation, cell-glycan extracellular interactions, and protein glycation/oxidation, functions related to the tissue mechanics and adhesion. CONCLUSIONS: We provide an in vivo demonstration of the anti-ageing benefit of glycerol at high dose (20%) reflected by a cumulative skin surface softening effect. The use of high moisturizing potent formulations should bring additional performance to other conventional moisturizing formulations.

The Effects of Mucopolysaccharide Polysulfate on Steroid-Induced Tight Junction Barrier Dysfunction in Human Epidermal Keratinocytes and a 3D Skin Model.

INTRODUCTION: The long-term use of topical corticosteroids (TCS) is associated with side effects such as skin atrophy and barrier deterioration. Moisturizers, such as mucopolysaccharide polysulfate (MPS), have been reported to prevent relapses in atopic dermatitis (AD) when used in combination with TCS. However, the mechanisms underlying the positive effects of MPS in combination with TCS in AD are poorly understood. In the present study, we investigated the effects of MPS in combination with clobetasol 17-propionate (CP) on tight junction (TJ) barrier function in human epidermal keratinocytes (HEKa) and 3D skin models. METHODS: The expression of claudin-1, which is crucial for TJ barrier function in keratinocytes, and transepithelial electrical resistance (TEER) was measured in CP-treated human keratinocytes incubated with and without MPS. A TJ permeability assay, using Sulfo-NHS-Biotin as a tracer, was also conducted in a 3D skin model. RESULTS: CP reduced claudin-1 expression and TEER in human keratinocytes, whereas MPS inhibited these CP-induced effects. Moreover, MPS inhibited the increase in CP-induced TJ permeability in a 3D skin model. CONCLUSION: The present study demonstrated that MPS improved TJ barrier impairment induced by CP. The improvement of TJ barrier function may partially be responsible for the delayed relapse of AD induced by the combination of MPS and TCS.