Characterization of Weissella viridescens UCO-SMC3 as a Potential Probiotic for the Skin: Its Beneficial Role in the Pathogenesis of Acne Vulgaris

Previously, we isolated lactic acid bacteria from the slime of the garden snail Helix aspersa Müller and selected Weissella viridescens UCO-SMC3 because of its ability to inhibit in vitro the growth of the skin-associated pathogen Cutibacterium acnes. The present study aimed to characterize the antimicrobial and immunomodulatory properties of W. viridescens UCO-SMC3 and to demonstrate its beneficial effect in the treatment of acne vulgaris. Our in vitro studies showed that the UCO-SMC3 strain resists adverse gastrointestinal conditions, inhibits the growth of clinical isolates of C. acnes, and reduces the adhesion of the pathogen to keratinocytes. Furthermore, in vivo studies in a mice model of C. acnes infection demonstrated that W. viridescens UCO-SMC3 beneficially modulates the immune response against the skin pathogen. Both the oral and topical administration of the UCO-SCM3 strain was capable of reducing the replication of C. acnes in skin lesions and beneficially modulating the inflammatory response. Of note, orally administered W. viridescens UCO-SMC3 induced more remarkable changes in the immune response to C. acnes than the topical treatment. However, the topical administration of W. viridescens UCO-SMC3 was more efficient than the oral treatment to reduce pathogen bacterial loads in the skin, and effects probably related to its ability to inhibit and antagonize the adhesion of C. acnes. Furthermore, a pilot study in acne volunteers demonstrated the capacity of a facial cream containing the UCO-SMC3 strain to reduce acne lesions. The results presented here encourage further mechanistic and clinical investigations to characterize W. viridescens UCO-SMC3 as a probiotic for acne vulgaris treatment.

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Self-Nanoemulsion Loaded with a Combination of Isotretinoin, an Anti-Acne Drug, and Quercetin: Preparation, Optimization, and In Vivo Assessment

Pharmaceutics ◽

10.3390/pharmaceutics13010046 ◽

2020 ◽

Vol 13 (1) ◽

pp. 46

Author(s):

Khaled M. Hosny ◽

Khalid S. Al Nahyah ◽

Nabil A. Alhakamy

Keyword(s):

Ex Vivo ◽

Acne Vulgaris ◽

Topical Administration ◽

Hepatoprotective Activity ◽

In Vivo Studies ◽

Enhanced Solubility ◽

Staphyloccocus Aureus ◽

Common Skin

Acne vulgaris is a common skin disease that affects everybody at least once in their lives. The treatment is challenging because the stratum corneum contains rigid corneocytes surrounded by intercellular lamellae that are difficult to bypass. In the present study, we intended to formulate an effective nanoemulsion that could deliver isotretinoin (ITT) with enhanced solubility, permeability, and bioavailability across the skin. ITT can have a serious hepatotoxic effect if given too frequently or erratically. Therefore, to overcome the aforesaid limitation, quercetin (QRS), a hepatoprotective agent, was incorporated into the formulation. Initially, the ITT solubility was determined in various surfactants and cosurfactants to select the essential ingredients to be used in the formulation and to optimize a nanoemulsion that could enhance the solubility and permeability of ITT and its antimicrobial activity against Staphyloccocus aureus, which is the main microorganism responsible for acne vulgaris. The mixture design was applied to study the interactions and optimize the independent variables that could match the prerequisites of selected dependent responses. A formulation containing 0.25 g of rosehip oil, 0.45 g of surfactant (Lauroglycol-90), and 0.3 g of cosurfactant (propylene glycol) was chosen as an optimized desirable formulation. The optimized batch was loaded with QRS and evaluated for in vitro and ex vivo permeation. The in vivo hepatotoxicity was assessed through topical administration. Permeability studies confirmed the enhanced permeation percentage of ITT (52.11 ± 2.85%) and QRS (25.44 ± 3.18%) of the optimized formulation, with an enhanced steady-state flux (Jss). The in vivo studies conducted on experimental animals demonstrated superior hepatoprotective activity of the prepared optimized formulation compared with other formulations of drugs and commercially marketed products. We anticipate that this optimized ITT formulation, followed up with good clinical evaluations, can be a breakthrough in the safe treatment of acne vulgaris.

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Activation of Deoxyribonuclease I by Nicotinamide as a New Strategy to Attenuate Tetracycline-Resistant Biofilms of Cutibacterium acnes

Pharmaceutics ◽

10.3390/pharmaceutics13060819 ◽

2021 ◽

Vol 13 (6) ◽

pp. 819

Author(s):

Yi-Hsien Shih ◽

Donald Liu ◽

Yen-Chou Chen ◽

Ming-Hsuan Liao ◽

Woan-Ruoh Lee ◽

...

Keyword(s):

Acne Vulgaris ◽

Topical Administration ◽

Dnase I ◽

Adjunctive Treatment ◽

Kinetic Assay ◽

Surface Plasmon Resonance Analysis ◽

Cutaneous Infections ◽

Cutibacterium Acnes

Biofilms of Cutibacterium (C.) acnes (formerly Propionibacterium acnes) are responsible for the persistence and antibiotic resistance of acne vulgaris. In addition to the standard treatments for acne vulgaris, a common adjunctive treatment is the topical administration of nicotinamide (NAM). However, the effects of NAM on biofilms of C. acnes have never been explored. This study comprehensively investigates the effects of NAM against biofilms of C. acnes using in vitro and in vivo approaches. The results showed that NAM potentiated the efficacy of suboptimal dosing of tetracycline against C. acnes. Moreover, NAM alone decreased the formation and increased the degradation of biofilms in C. acnes. The antibiofilm effect of NAM against C. acnes was further enhanced in combination with deoxyribonuclease (DNase) I, an enzyme with known antibiofilm properties. The computational molecular docking, surface plasmon resonance analysis, and enzymatic kinetic assay demonstrated that NAM binds to DNase I and accelerated its reaction. In conclusion, NAM activates DNase I to attenuate biofilms of C. acnes. This offers valuable insights into the strategies against biofilms that are worth elaborating on in other biofilm-related chronic cutaneous infections in the future.

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A Novel Gold Calreticulin Nanocomposite Based on Chitosan for Wound Healing in a Diabetic Mice Model

Nanomaterials ◽

10.3390/nano9010075 ◽

2019 ◽

Vol 9 (1) ◽

pp. 75 ◽

Cited By ~ 10

Author(s):

Sara Paola Hernández Martínez ◽

Teodoro Iván Rivera González ◽

Moisés Armides Franco Molina ◽

Juan José Bollain y Goytia ◽

Juan José Martínez Sanmiguel ◽

...

Keyword(s):

Wound Healing ◽

Topical Administration ◽

Nuclear Antigen ◽

Histological Evaluation ◽

Mice Model ◽

Fibroblast Migration ◽

And Migration ◽

Proliferating Cell

The development of new nanomaterials to promote wound healing is rising, because of their topical administration and easy functionalization with molecules that can improve and accelerate the process of healing. A nanocomposite of gold nanoparticles (AuNPs) functionalized with calreticulin was synthetized and evaluated. The ability of the nanocomposite to promote proliferation and migration was determined in vitro, and in vivo wound healing was evaluated using a mice model of diabetes established with streptozotocin (STZ). In vitro, the nanocomposite not affect the cell viability and the expression of proliferating cell nuclear antigen (PCNA). Moreover, the nanocomposite promotes the clonogenicity of keratinocytes, endothelial cells, and fibroblasts, and accelerates fibroblast migration. In vivo, mice treated with the nanocomposite presented significantly faster wound healing. The histological evaluation showed re-epithelization and the formation of granular tissue, as well as an increase of collagen deposition. Therefore, these results confirm the utility of AuNPs–calreticulin nanocomposites as potential treatment for wound healing of diabetic ulcers.

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Inhibitory Effects of a Sargassum miyabei Yendo on Cutibacterium acnes-Induced Skin Inflammation

Nutrients ◽

10.3390/nu12092620 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2620

Author(s):

Mi-Jin Yim ◽

Jeong Min Lee ◽

Hyun-Soo Kim ◽

Grace Choi ◽

Young-Mog Kim ◽

...

Keyword(s):

Acne Vulgaris ◽

Skin Lesions ◽

Enzyme Linked Immunosorbent Assay ◽

Hacat Cells ◽

Chronic Inflammatory Condition ◽

Cutibacterium Acnes ◽

Anti Inflammatory ◽

Sargassum Miyabei

Acne vulgaris is a chronic inflammatory condition of skin sebaceous follicles. To explore its effects on acne vulgaris, we investigated the antibacterial and anti-inflammatory activities of Sargassum miyabei Yendo (a brown alga) ethanolic extract (SMYEE) on Cutibacterium acnes (C. acnes)-stimulated inflammatory responses, both in vivo and in vitro. To induce inflammation in vivo, C. acnes was intradermally injected into the dorsal skin of mice, to which SMYEE was applied. The antimicrobial activity of SMYEE was evaluated by the determination of minimum inhibitory concentrations (MICs). To explore in vitro anti-inflammatory effects, HaCaT cells were stimulated with C. acnes after treatment with SMYEE. The levels of IL-8 and the underlying molecular effects in C. acnes-stimulated HaCaT cells were assessed by enzyme-linked immunosorbent assay, Western blotting, and an electrophoretic mobility shift assay. Mouse skin lesions improved after treatment with SMYEE (50 μg/mouse). Neutrophil infiltration was significantly reduced in SMYEE-treated compared to SMYEE-untreated skin lesions. SMYEE reversed the C. acnes-induced increase in IL-8 levels in HaCaT cells and suppressed dHL-60 cell migration. SMYEE also inhibited C. acnes-induced phosphorylation of the extracellular signal-regulated kinase and inhibited activator protein-1 signaling. SMYEE may be a useful treatment for C. acnes-induced acne vulgaris.

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Angiostatic activity of the antitumor cytokine interleukin-21

Blood ◽

10.1182/blood-2007-09-113878 ◽

2008 ◽

Vol 112 (13) ◽

pp. 4940-4947 ◽

Cited By ~ 36

Author(s):

Karolien Castermans ◽

Sebastien P. Tabruyn ◽

Rong Zeng ◽

Judy R. van Beijnum ◽

Cheryl Eppolito ◽

...

Keyword(s):

Immune Response ◽

Tumor Angiogenesis ◽

Chorioallantoic Membrane ◽

Antitumor Immune Response ◽

In Vivo Studies ◽

Type I ◽

Stat3 Phosphorylation ◽

Interleukin 21

Abstract Interleukin-21 (IL-21) is a recently described immunoregulatory cytokine. It has been identified as a very potent immunotherapeutic agent in several cancer types in animal models, and clinical studies are ongoing. IL-21 belongs to the type I cytokine family of which other members, ie, IL-2, IL-15, and IL-4, have been shown to exert activities on vascular endothelial cells (ECs). We hypothesized that IL-21, in addition to inducing the antitumor immune response, also inhibits tumor angiogenesis. In vitro experiments showed a decrease of proliferation and sprouting of activated ECs after IL-21 treatment. We found that the IL-21 receptor is expressed on vascular ECs. Furthermore, in vivo studies in the chorioallantoic membrane of the chick embryo and in mouse tumors demonstrated that IL-21 treatment disturbs vessel architecture and negatively affects vessel outgrowth. Our results also confirm the earlier suggested angiostatic potential of IL-2 in vitro and in vivo. The angiostatic effect of IL-21 is confirmed by the decrease in expression of angiogenesis-related genes. Interestingly, IL-21 treatment of ECs leads to a decrease of Stat3 phosphorylation. Our research shows that IL-21 is a very powerful antitumor compound that combines the induction of an effective antitumor immune response with inhibition of tumor angiogenesis.

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The Comparative Analysis of Antiviral Activity of Native and Modified Fucoidans from Brown Algae Fucus evanescens In Vitro and In Vivo

Marine Drugs ◽

10.3390/md18040224 ◽

2020 ◽

Vol 18 (4) ◽

pp. 224 ◽

Cited By ~ 8

Author(s):

Natalya V. Krylova ◽

Svetlana P. Ermakova ◽

Vyacheslav F. Lavrov ◽

Irina A. Leneva ◽

Galina G. Kompanets ◽

...

Keyword(s):

Antiviral Activity ◽

Brown Algae ◽

Biological Activities ◽

Intraperitoneal Administration ◽

In Vivo Studies ◽

Mice Model ◽

Dna And Rna ◽

Antiviral Activities

The enzymatic depolymerization of fucoidans from brown algae allowed the production of their standardized derivatives with different biological activities. This work aimed to compare the antiviral activities of native (FeF) and modified with enzyme (FeHMP) fucoidans from F. evanescens. The cytotoxicity and antiviral activities of the FeF and FeHMP against herpes viruses (HSV-1, HSV-2), enterovirus (ECHO-1), and human immunodeficiency virus (HIV-1) in Vero and human MT-4 cell lines were examined by methylthiazolyltetrazolium bromide (MTT) and cytopathic effect (CPE) reduction assays, respectively. The efficacy of fucoidans in vivo was evaluated in the outbred mice model of vaginitis caused by HSV-2. We have shown that both FeF and FeHMP significantly inhibited virus-induced CPE in vitro and were more effective against HSV. FeF exhibited antiviral activity against HSV-2 with a selective index (SI) > 40, and FeHMP with SI ˃ 20, when they were added before virus infection or at the early stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that after intraperitoneal administration (10 mg/kg), both FeF and FeHMP protected mice from lethal intravaginal HSV-2 infection to approximately the same degree (44–56%). Thus, FeF and FeHMP have comparable potency against several DNA and RNA viruses, allowing us to consider the studied fucoidans as promising broad-spectrum antivirals.

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Propionibacterium (Cutibacterium) granulosum Extracellular DNase BmdE Targeting Propionibacterium (Cutibacterium) acnes Biofilm Matrix, a Novel Inter-Species Competition Mechanism

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.809792 ◽

2022 ◽

Vol 11 ◽

Author(s):

Vicky Bronnec ◽

Hinnerk Eilers ◽

Anika C. Jahns ◽

Hélène Omer ◽

Oleg A. Alexeyev

Keyword(s):

Extracellular Matrix ◽

Acne Vulgaris ◽

Opportunistic Pathogen ◽

Resistant Bacteria ◽

Skin Microbiome ◽

Cutibacterium Acnes ◽

Propionibacterium Granulosum ◽

Extracellular Nuclease

Acne vulgaris is the most common dermatological disorder worldwide affecting more than 80% of adolescents and young adults with a global prevalence of 231 million cases in 2019. The involvement of the skin microbiome disbalance in the pathophysiology of acne is recognized, especially regarding the relative abundance and diversity of Propionibacterium acnes a well-known dominant human skin commensal. Biofilms, where bacteria are embedded into a protective polymeric extracellular matrix, are the most prevalent life style for microorganisms. P. acnes and its biofilm-forming ability is believed to be a contributing factor in the development of acne vulgaris, the persistence of the opportunistic pathogen and antibiotic therapy failures. Degradation of the extracellular matrix is one of the strategies used by bacteria to disperse the biofilm of competitors. In this study, we report the identification of an endogenous extracellular nuclease, BmdE, secreted by Propionibacterium granulosum able to degrade P. acnes biofilm both in vivo and in vitro. This, to our knowledge, may represent a novel competitive mechanism between two closely related species in the skin. Antibiotics targeting P. acnes have been the mainstay in acne treatment. Extensive and long-term use of antibiotics has led to the selection and spread of resistant bacteria. The extracellular DNase BmdE may represent a new bio-therapeutical strategy to combat P. acnes biofilm in acne vulgaris.

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Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22179262 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9262

Author(s):

Huey-Shan Hung ◽

Kai-Bo Chang ◽

Cheng-Ming Tang ◽

Tian-Ren Ku ◽

Mei-Lang Kung ◽

...

Keyword(s):

Stem Cells ◽

Immune Response ◽

Silver Nanoparticles ◽

Mesenchymal Stem Cells ◽

Superior Performance ◽

In Vivo Studies ◽

Vascular Regeneration ◽

Anti Inflammatory

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton’s jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials.

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Recruitment of Immune Effector Cells against Glioblastoma-Multiforme by a MHC-Chlorotoxin Chimeric Protein

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2016.331 ◽

2016 ◽

Vol 43 (S4) ◽

pp. S1-S1

Author(s):

O. Cohen-Inbar

Keyword(s):

Immune Response ◽

Glioblastoma Multiforme ◽

Cytotoxic T Cells ◽

Chimeric Protein ◽

Human Leukocyte ◽

In Vivo Studies ◽

Great Promise ◽

Single Chain

Glioblastoma Multiforme is the most common malignant primary brain tumor, having a mean overall survival <2 years. The lack of an efficient immune response against the tumor have been attributed to its immunosuppressive capabilities and an immunosuppressing local environment. Aim: We set out to design a chimeric molecule that recognizes and binds tissue inducible metalloproteinase known to be induced in GBM cells (MMP-2) on one end. Its other end, the effector domain, mobilizes and recruits cytotoxic T-cells to mount an effective anti-tumor reaction. Methods: The targeting moiety is the small 36-amino acids Chlorotoxin, derived from the venom of the Israeli Yellow scorpion. The effector end is a single chain HLA-A2 (Human leukocyte antigen subtype A2) covalently bound to phosphoprotein-65 derived from the cytomegalovirus, to which most of the human population has developed a specific immune response. Results: The molecular construct was cloned and expressed in E.coli. The protein product was isolated, purified, and then folded in vitro. Various activity assays employed demonstrated retained activity of each domain, including flow-cytometry, intracellular staining, fluorescence immunohistochemistry, radiolabeled toxicity assays etc. Initial in-vivo studies show great promise. Conclusions: We present a proof of concept study for a new immunotherapy approach to battle GBM. A molecular construct which contains a non-antibody compact and highly specific targeting domain, combined with the ability to recruit anti-CMV T-cell lymphocyte population. The recruitment of potent memory CTL’s to the tumor’s milieu may prove resistant to the previously described local immunosuppressive environment brought about by the tumor.

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In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01722-18 ◽

2018 ◽

Vol 63 (3) ◽

Cited By ~ 7

Author(s):

Rafael A. Guerra ◽

Marcos P. Silva ◽

Tais C. Silva ◽

Maria C. Salvadori ◽

Fernanda S. Teixeira ◽

...

Keyword(s):

Egg Production ◽

Oral Treatment ◽

Drug Repurposing ◽

In Vivo Studies ◽

Content Type ◽

Low Concentrations ◽

Parasitic Flatworm ◽

And Control

ABSTRACT Schistosomiasis is a parasitic flatworm disease that infects over 200 million people worldwide, especially in poor communities. Treatment and control of the disease rely on just one drug, praziquantel. Since funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, from a screening of 13 marketed diuretics, we identified that spironolactone, a potassium-sparing diuretic, had potent antischistosomal effects on Schistosoma mansoni in vitro and in vivo in a murine model of schistosomiasis. In vitro, spironolactone at low concentrations (<10 µM) is able to alter worm motor activity and the morphology of adult schistosomes, leading to parasitic death. In vivo, oral treatment with spironolactone at a single dose (400 mg/kg) or daily for five consecutive days (100 mg/kg/day) in mice harboring either patent or prepatent infections significantly reduced worm burden, egg production, and hepato- and splenomegaly (P < 0.05 to P < 0.001). Taken together, with the safety profile of spironolactone, supported by its potential to affect schistosomes, these results indicate that spironolactone could be a potential treatment for schistosomiasis and make it promising for repurposing.

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