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1
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Wang Z, Wang M, Tao Q, Li Y, Wang H, Zhang M, Liu X, Zhang J. Betaine-salicylic acid cocrystal for enhanced skincare and acne treatment. RSC Med Chem 2025:d5md00001g. [PMID: 40027344 PMCID: PMC11865917 DOI: 10.1039/d5md00001g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Accepted: 02/04/2025] [Indexed: 03/05/2025] Open
Abstract
Salicylic acid (SA) is a natural lipophilic active ingredient commonly used in cosmetics and skin disease treatments, offering benefits such as exfoliation, anti-inflammation effects, antibacterial properties, oil control, and acne alleviation. However, its poor water solubility, low bioavailability, and potential side effects, such as allergies, irritation, and dryness, hinder its widespread application. In this study, we prepared a betaine-salicylic acid (BeSA) cocrystal and systematically characterized its crystal structure, biological activity, and clinical efficacy. The results showed that BeSA has significantly lower irritancy and cytotoxicity than SA, but exhibits excellent anti-inflammatory and antioxidant properties as well as high moisturizing and anti-acne efficacy, making it a potential alternative to SA. Further, quantum chemical calculations and molecular docking simulations were conducted to investigate the intrinsic mechanisms underlying the excellent bioactivity of BeSA cocrystals. This study introduces an innovative solution for safer and more effective skincare formulations based on SA and offers theoretical guidance regarding material engineering and further material optimization, which has crucial implications for both industry and academia.
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Affiliation(s)
- Zhenyuan Wang
- Sauvage Laboratory for Smart Materials, School of Materials Science and Engineering, Harbin Institute of Technology (Shenzhen) Shenzhen 518055 China
- Shenzhen Shinehigh Innovation Technology Co., Ltd. Shenzhen 518055 China
| | - Mi Wang
- Sauvage Laboratory for Smart Materials, School of Materials Science and Engineering, Harbin Institute of Technology (Shenzhen) Shenzhen 518055 China
| | - Qingsheng Tao
- Advanced Research, L'Oreal Research & Innovation China Shanghai 201206 China
| | - Yufei Li
- The Centre in Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences, Macao Polytechnic University Macao 999078 China
| | - Hao Wang
- Sauvage Laboratory for Smart Materials, School of Materials Science and Engineering, Harbin Institute of Technology (Shenzhen) Shenzhen 518055 China
| | - Mei Zhang
- Advanced Research, L'Oreal Research & Innovation China Shanghai 201206 China
| | - Xueli Liu
- Advanced Research, L'Oreal Research & Innovation China Shanghai 201206 China
| | - Jiaheng Zhang
- Sauvage Laboratory for Smart Materials, School of Materials Science and Engineering, Harbin Institute of Technology (Shenzhen) Shenzhen 518055 China
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2
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Essam R, Nasr M, Khater MW, Fayez B, Anis N. Anti-microbial impact of non-antibiotic agents; salicylic acid, N-acetylcysteine, and isotretinoin against Cutibacterium acnes in patients with acne vulgaris. Arch Dermatol Res 2024; 317:155. [PMID: 39739120 DOI: 10.1007/s00403-024-03608-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/17/2024] [Accepted: 11/26/2024] [Indexed: 01/02/2025]
Abstract
There are two main strategies to eliminate Cutibacterium acnes and to reduce antibiotic resistance in acne treatment. The first is to target the pathogenic bacteria and the second is to change the environment for their growth. The present study aimed to evaluate the anti-microbial role of non-antibiotic agents against Cutibacterium acnes (C. acnes) in acne vulgaris patients. The three agents of interest in the study were isotretinoin, salicylic acid, and N-acetylcysteine (NAC). The study included forty-eight patients with acne vulgaris with ages ranging from 16 to 30 years, and they had different grades of the disease. Azithromycin and Doxycycline sensitivity and the ability of biofilm formation of C. acnes isolated from all patients were assessed before and after adding the 3 agents. Azithromycin and Doxycycline sensitivity was improved after adding the 3 agents and the ability of biofilm formation of C. acnes was also reduced. Isotretinoin, salicylic acid, and NAC can be promising adjuvants in treating acne vulgaris by their anti-microbial effect in reducing biofilm formation and improving antibiotic sensitivity. Clinical Trial NCT06179056.
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Affiliation(s)
- Reham Essam
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
| | - Mohamed Nasr
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Maha W Khater
- Medical Microbiology and Immunology Department, Zagazig University, Zagazig, Egypt
| | - Basma Fayez
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Nourhan Anis
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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3
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Karabatić Knezović S, Knezović D, Matana A, Puizina Ivić N, Drmić Hofman I. Strong association of TLR2 and TLR3 polymorphisms with keratoacanthoma and common warts: a case-control study. Croat Med J 2024; 65:232-238. [PMID: 38868969 PMCID: PMC11157254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 05/09/2024] [Indexed: 06/14/2024] Open
Abstract
AIM To determine variations in allele and genotype frequencies between keratoacanthoma (KA) and common warts (CW), compared with the control group, in three single nucleotide polymorphisms (SNPs) within the TLR2, TLR3, and TLR9 genes. METHODS This case-control study involved samples from 161 patients with KA, 152 patients with CW, and 469 controls. DNA was isolated from formalin-fixed paraffin-embedded tissue sections. Three SNPs - rs4696480 in TLR2, rs7657186 in TLR9, and rs35213 in TLR3 - were genotyped with TaqMan Genotyping Assays on the 7500 Real-Time PCR System. RESULTS TLR2 rs4696480 and TLR3 rs7657186 were significantly overrepresented in KA and CW compared with controls (P<0.001). The association was stronger for CW than for KA, as evidenced by higher frequencies of the A allele and AA genotype for rs4696480. Both KA and CW patients had higher frequencies of the G allele and GG genotype for rs7657186 than controls. rs7657186 was moderately associated with KA and CW, with the G allele and GG genotype being more prevalent in CW cases, where no AA homozygotes were found. CONCLUSION Genetic variants in TLR2 (rs4696480) and TLR3 (rs7657186) genes may affect KA and CW development, influencing immune responses and susceptibility to these skin lesions. Further research is required to elucidate TLR expression patterns and their role in KA development.
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Affiliation(s)
| | | | | | | | - Irena Drmić Hofman
- Irena Drmić Hofman, Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Šoltanska 2, 21000 Split, Croatia,
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Kumar V, Stewart Iv JH. Pattern-Recognition Receptors and Immunometabolic Reprogramming: What We Know and What to Explore. J Innate Immun 2024; 16:295-323. [PMID: 38740018 PMCID: PMC11250681 DOI: 10.1159/000539278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 05/07/2024] [Indexed: 05/16/2024] Open
Abstract
BACKGROUND Evolutionarily, immune response is a complex mechanism that protects the host from internal and external threats. Pattern-recognition receptors (PRRs) recognize MAMPs, PAMPs, and DAMPs to initiate a protective pro-inflammatory immune response. PRRs are expressed on the cell membranes by TLR1, 2, 4, and 6 and in the cytosolic organelles by TLR3, 7, 8, and 9, NLRs, ALRs, and cGLRs. We know their downstream signaling pathways controlling immunoregulatory and pro-inflammatory immune response. However, the impact of PRRs on metabolic control of immune cells to control their pro- and anti-inflammatory activity has not been discussed extensively. SUMMARY Immune cell metabolism or immunometabolism critically determines immune cells' pro-inflammatory phenotype and function. The current article discusses immunometabolic reprogramming (IR) upon activation of different PRRs, such as TLRs, NLRs, cGLRs, and RLRs. The duration and type of PRR activated, species studied, and location of immune cells to specific organ are critical factors to determine the IR-induced immune response. KEY MESSAGE The work herein describes IR upon TLR, NLR, cGLR, and RLR activation. Understanding IR upon activating different PRRs is critical for designing better immune cell-specific immunotherapeutics and immunomodulators targeting inflammation and inflammatory diseases.
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Affiliation(s)
- Vijay Kumar
- Department of Surgery, Laboratory of Tumor Immunology and Immunotherapy, Medical Education Building-C, Morehouse School of Medicine, Atlanta, Georgia, USA
| | - John H Stewart Iv
- Department of Surgery, Laboratory of Tumor Immunology and Immunotherapy, Medical Education Building-C, Morehouse School of Medicine, Atlanta, Georgia, USA
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Dai Z, Hu J, Luo Z, Xiao J. Downregulation of circ_0035292 Alleviates LPS-Induced WI-38 Cell Injury via Targeting miR-494-3p/TLR4 Pathway in Infantile Pneumonia. Biochem Genet 2024; 62:915-930. [PMID: 37500967 DOI: 10.1007/s10528-023-10455-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 07/12/2023] [Indexed: 07/29/2023]
Abstract
Circular RNAs (circRNAs) have been confirmed to mediate infantile pneumonia development. In this, we investigated the role and new mechanism of circ_0035292 regulating infantile pneumonia progression. Lipopolysaccharide (LPS)-treated WI-38 cells were used to mimic infantile pneumonia cell injury models. Quantitative real-time PCR was used to measure circ_0035292, microRNA (miR)-494-3p and toll-like receptor 4 (TLR4). Cell proliferation and apoptosis were assessed by MTT assay, EdU assay, and flow cytometry. Protein expression was tested using western blot analysis. Inflammation and oxidative stress were evaluated by measuring IL-6, IL-1β, MDA and SOD levels using ELISA assay and corresponding kits. RNA interaction was confirmed by dual-luciferase reporter assay and RIP assay. Circ_0035292 had elevated expression in infantile pneumonia patients and LPS-induced WI-38 cells. Silenced circ_0035292 could enhance WI-38 cell proliferation, while suppress apoptosis, inflammation and oxidative stress under LPS treatment. Mechanically, circ_0035292 targeted miR-494-3p to positively regulate TLR4. The rescue experiments indicated that miR-494-3p inhibitor abolished the function of circ_0035292 knockdown, and TLR4 overexpression reversed the inhibitory effect of miR-494-3p on LPS-induced WI-38 cell injury. Circ_0035292 might be a potential target for infantile pneumonia treatment, which knockdown could relieve LPS-induced cell injury via the regulation of miR-494-3p/TLR4 axis.
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Affiliation(s)
- Zhenzhao Dai
- Department of Pediatrics, Affiliated Hospital of Jinggangshan University, Ji'an, Jiangxi, China
| | - Jiansheng Hu
- Jinggangshan University, 28 Xueyuan Road, Qingyuan District, Ji'an, 343000, Jiangxi, China
| | - Zhiying Luo
- Jinggangshan University, 28 Xueyuan Road, Qingyuan District, Ji'an, 343000, Jiangxi, China
| | - Jianhua Xiao
- Jinggangshan University, 28 Xueyuan Road, Qingyuan District, Ji'an, 343000, Jiangxi, China.
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Sánchez-Pellicer P, Eguren-Michelena C, García-Gavín J, Llamas-Velasco M, Navarro-Moratalla L, Núñez-Delegido E, Agüera-Santos J, Navarro-López V. Rosacea, microbiome and probiotics: the gut-skin axis. Front Microbiol 2024; 14:1323644. [PMID: 38260914 PMCID: PMC10800857 DOI: 10.3389/fmicb.2023.1323644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 12/26/2023] [Indexed: 01/24/2024] Open
Abstract
Rosacea is an inflammatory skin disease involving diverse symptoms with a variable clinical progress which can severely impact the patient's quality of life as well as their mental health. The pathophysiological model of rosacea involves an unbalanced immune system predisposed to excessive inflammation, in addition to vascular and nervous alterations, being certain cutaneous microorganisms' triggers of the symptoms onset. The gut-skin axis explains a bidirectional interaction between skin and gut microbiota in some inflammatory skin diseases such as atopic dermatitis, psoriasis, or rosacea. The introduction and consolidation of the next-generation sequencing in recent years has provided unprecedented information about the microbiome. However, the characterization of the gut and skin microbiota and the impact of the gut-skin axis in patients with rosacea has been little explored, in contrast to other inflammatory skin diseases such as atopic dermatitis or psoriasis. Furthermore, the clinical evolution of patients with rosacea is not always adequate and it is common for them to present a sustained symptomatology with frequent flare-ups. In this context, probiotic supplementation could improve the clinical evolution of these patients as happens in other pathologies. Through this review we aim to establish and compile the basics and directions of current knowledge to understand the mechanisms by which the microbiome influences the pathogenesis of rosacea, and how modulation of the skin and gut microbiota could benefit these patients.
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Affiliation(s)
- Pedro Sánchez-Pellicer
- MiBioPath Research Group, Faculty of Medicine, Catholic University of Murcia (UCAM), Guadalupe, Spain
| | | | | | - Mar Llamas-Velasco
- Department of Dermatology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Laura Navarro-Moratalla
- MiBioPath Research Group, Faculty of Medicine, Catholic University of Murcia (UCAM), Guadalupe, Spain
| | - Eva Núñez-Delegido
- MiBioPath Research Group, Faculty of Medicine, Catholic University of Murcia (UCAM), Guadalupe, Spain
| | - Juan Agüera-Santos
- MiBioPath Research Group, Faculty of Medicine, Catholic University of Murcia (UCAM), Guadalupe, Spain
| | - Vicente Navarro-López
- MiBioPath Research Group, Faculty of Medicine, Catholic University of Murcia (UCAM), Guadalupe, Spain
- Infectious Diseases Unit, Department of Internal Medicine, University Hospital of Vinalopó-Fisabio, Elche, Spain
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Kumar V, Stewart JH. Immune Homeostasis: A Novel Example of Teamwork. Methods Mol Biol 2024; 2782:1-24. [PMID: 38622389 DOI: 10.1007/978-1-0716-3754-8_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2024]
Abstract
All living organisms must maintain homeostasis to survive, reproduce, and pass their traits on to the next generation. If homeostasis is not maintained, it can result in various diseases and ultimately lead to death. Physiologists have coined the term "homeostasis" to describe this process. With the emergence of immunology as a separate branch of medicine, the concept of immune homeostasis has been introduced. Maintaining immune homeostasis is crucial to support overall homeostasis through different immunological and non-immunological routes. Any changes in the immune system can lead to chronic inflammatory or autoimmune diseases, immunodeficiency diseases, frequent infections, and cancers. Ongoing scientific advances are exploring new avenues in immunology and immune homeostasis maintenance. This chapter introduces the concept of immune homeostasis and its maintenance through different mechanisms.
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Affiliation(s)
- Vijay Kumar
- Department of Surgery, Laboratory of Tumor Immunology and Immunotherapy, Medical Education Building-C, Morehouse School of Medicine, Atlanta, GA, USA
| | - John H Stewart
- Department of Surgery, Laboratory of Tumor Immunology and Immunotherapy, Medical Education Building-C, Morehouse School of Medicine, Atlanta, GA, USA.
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8
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Wang W, Hwang S, Park D, Park YD. The Features of Shared Genes among Transcriptomes Probed in Atopic Dermatitis, Psoriasis, and Inflammatory Acne: S100A9 Selection as the Target Gene. Protein Pept Lett 2024; 31:356-374. [PMID: 38766834 DOI: 10.2174/0109298665290166240426072642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 03/30/2024] [Accepted: 04/05/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND Atopic dermatitis (AD), psoriasis (PS), and inflammatory acne (IA) are well-known as inflammatory skin diseases. Studies of the transcriptome with altered expression levels have reported a large number of dysregulated genes and gene clusters, particularly those involved in inflammatory skin diseases. OBJECTIVE To identify genes commonly shared in AD, PS, and IA that are potential therapeutic targets, we have identified consistently dysregulated genes and disease modules that overlap with AD, PS, and IA. METHODS Microarray data from AD, PS, and IA patients were downloaded from Gene Expression Omnibus (GEO), and identification of differentially expressed genes from microarrays of AD, PS, and IA was conducted. Subsequently, gene ontology and gene set enrichment analysis, detection of disease modules with known disease-associated genes, construction of the protein-protein interaction (PPI) network, and PPI sub-mapping analysis of shared genes were performed. Finally, the computational docking simulations between the selected target gene and inhibitors were conducted. RESULTS We identified 50 shared genes (36 up-regulated and 14 down-regulated) and disease modules for each disease. Among the shared genes, 20 common genes in PPI network were detected such as LCK, DLGAP5, SELL, CEP55, CDC20, RRM2, S100A7, S100A9, MCM10, AURKA, CCNB1, CHEK1, BTC, IL1F7, AGTR1, HABP4, SERPINB13, RPS6KA4, GZMB, and TRIP13. Finally, S100A9 was selected as the target gene for therapeutics. Docking simulations between S100A9 and known inhibitors indicated several key binding residues, and based on this result, we suggested several cannabinoids such as WIN-55212-2, JZL184, GP1a, Nabilone, Ajulemic acid, and JWH-122 could be potential candidates for a clinical study for AD, PS, and IA via inhibition of S100A9-related pathway. CONCLUSION Overall, our approach may become an effective strategy for discovering new disease candidate genes for inflammatory skin diseases with a reevaluation of clinical data.
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Affiliation(s)
- Wei Wang
- College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, P.R. China
| | - Sungbo Hwang
- Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, 34114, Korea
| | - Daeui Park
- Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, 34114, Korea
| | - Yong-Doo Park
- College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, P.R. China
- Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing, 314006, P.R. China
- Skin Diseases Research Center, Yangtze Delta Region Institute of Tsinghua University, Jiaxing, P.R. China
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9
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Ackerman L, Acloque G, Bacchelli S, Schwartz H, Feinstein BJ, La Stella P, Alavi A, Gollerkeri A, Davis J, Campbell V, McDonald A, Agarwal S, Karnik R, Shi K, Mishkin A, Culbertson J, Klaus C, Enerson B, Massa V, Kuhn E, Sharma K, Keaney E, Barnes R, Chen D, Zheng X, Rong H, Sabesan V, Ho C, Mainolfi N, Slavin A, Gollob JA. IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial. Nat Med 2023; 29:3127-3136. [PMID: 37957373 PMCID: PMC10719089 DOI: 10.1038/s41591-023-02635-7] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 10/06/2023] [Indexed: 11/15/2023]
Abstract
Toll-like receptor-driven and interleukin-1 (IL-1) receptor-driven inflammation mediated by IL-1 receptor-associated kinase 4 (IRAK4) is involved in the pathophysiology of hidradenitis suppurativa (HS) and atopic dermatitis (AD). KT-474 (SAR444656), an IRAK4 degrader, was studied in a randomized, double-blind, placebo-controlled phase 1 trial where the primary objective was safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics and clinical activity in patients with moderate to severe HS and in patients with moderate to severe AD. KT-474 was administered as a single dose and then daily for 14 d in 105 healthy volunteers (HVs), followed by dosing for 28 d in an open-label cohort of 21 patients. Degradation of IRAK4 was observed in HV blood, with mean reductions after a single dose of ≥93% at 600-1,600 mg and after 14 daily doses of ≥95% at 50-200 mg. In patients, similar IRAK4 degradation was achieved in blood, and IRAK4 was normalized in skin lesions where it was overexpressed relative to HVs. Reduction of disease-relevant inflammatory biomarkers was demonstrated in the blood and skin of patients with HS and patients with AD and was associated with improvement in skin lesions and symptoms. There were no drug-related infections. These results, from what, to our knowledge, is the first published clinical trial using a heterobifunctional degrader, provide initial proof of concept for KT-474 in HS and AD to be further confirmed in larger trials. ClinicalTrials.gov identifier: NCT04772885 .
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | - Kelvin Shi
- Kymera Therapeutics, Inc., Watertown, MA, USA
| | | | | | | | | | | | - Eric Kuhn
- Kymera Therapeutics, Inc., Watertown, MA, USA
| | | | - Erin Keaney
- Kymera Therapeutics, Inc., Watertown, MA, USA
| | | | - Dapeng Chen
- Kymera Therapeutics, Inc., Watertown, MA, USA
| | | | | | | | - Chris Ho
- Kymera Therapeutics, Inc., Watertown, MA, USA
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10
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Gao X, Wang Z, Du L. Glial Cells and Itch: Possible Targets for Novel Antipruritic Therapies. ACS Chem Neurosci 2023; 14:331-339. [PMID: 36655585 DOI: 10.1021/acschemneuro.2c00638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Glial cells, which are the non-neuronal cells of the nervous system, play essential roles in brain development, homeostasis, and diseases. Glial cells have attracted attention because of their active involvement in many neurological disorders. In recent years, substantial progress has been made in our understanding of the roles of glial cells in the pathogenesis of itch. Mechanistically, central and peripheral glial cells modulate acute and chronic pruritus via different mechanisms. In this review, we present the current knowledge about the involvement of glial cells in the modulation of itch processing and the mechanism of glial cell activation under itch stimuli. Targeting glial cells may provide novel approaches for itch therapy.
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Affiliation(s)
- Xinyi Gao
- School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Zhifei Wang
- School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Lixia Du
- Department of Biochemistry, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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11
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Umair M, Jabbar S, Zhaoxin L, Jianhao Z, Abid M, Khan KUR, Korma SA, Alghamdi MA, El-Saadony MT, Abd El-Hack ME, Cacciotti I, AbuQamar SF, El-Tarabily KA, Zhao L. Probiotic-Based Bacteriocin: Immunity Supplementation Against Viruses. An Updated Review. Front Microbiol 2022; 13:876058. [PMID: 36033850 PMCID: PMC9402254 DOI: 10.3389/fmicb.2022.876058] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 04/14/2022] [Indexed: 11/13/2022] Open
Abstract
Viral infections are a major cause of severe, fatal diseases worldwide. Recently, these infections have increased due to demanding contextual circumstances, such as environmental changes, increased migration of people and product distribution, rapid demographic changes, and outbreaks of novel viruses, including the COVID-19 outbreak. Internal variables that influence viral immunity have received attention along with these external causes to avert such novel viral outbreaks. The gastrointestinal microbiome (GIM), particularly the present probiotics, plays a vital role in the host immune system by mediating host protective immunity and acting as an immune regulator. Bacteriocins possess numerous health benefits and exhibit antagonistic activity against enteric pathogens and immunobiotics, thereby inhibiting viral infections. Moreover, disrupting the homeostasis of the GIM/host immune system negatively affects viral immunity. The interactions between bacteriocins and infectious viruses, particularly in COVID-19, through improved host immunity and physiology are complex and have not yet been studied, although several studies have proven that bacteriocins influence the outcomes of viral infections. However, the complex transmission to the affected sites and siRNA defense against nuclease digestion lead to challenging clinical trials. Additionally, bacteriocins are well known for their biofunctional properties and underlying mechanisms in the treatment of bacterial and fungal infections. However, few studies have shown the role of probiotics-derived bacteriocin against viral infections. Thus, based on the results of the previous studies, this review lays out a road map for future studies on bacteriocins for treating viral infections.
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Affiliation(s)
- Muhammad Umair
- Department of Food Science and Engineering, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, China
- Key Laboratory of Optoelectronic Devices and Systems, College of Physics and Optoelectronic Engineering, Ministry of Education and Guangdong Province, Shenzhen University, Shenzhen, China
| | - Saqib Jabbar
- Food Science Research Institute (FSRI), National Agricultural Research Centre (NARC), Islamabad, Pakistan
| | - Lu Zhaoxin
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Zhang Jianhao
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Muhammad Abid
- Institute of Food and Nutritional Sciences, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan
| | - Kashif-Ur R. Khan
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Sameh A. Korma
- Department of Food Science, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
| | - Mashail A. Alghamdi
- Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohamed T. El-Saadony
- Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
| | | | - Ilaria Cacciotti
- Department of Engineering, INSTM RU, University of Rome “Niccolò Cusano”, Rome, Italy
| | - Synan F. AbuQamar
- Department of Biology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates
| | - Khaled A. El-Tarabily
- Department of Biology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates
- Khalifa Center for Genetic Engineering and Biotechnology, United Arab Emirates University, Al-Ain, United Arab Emirates
- Harry Butler Institute, Murdoch University, Murdoch, WA, Australia
| | - Liqing Zhao
- Department of Food Science and Engineering, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, China
- Key Laboratory of Optoelectronic Devices and Systems, College of Physics and Optoelectronic Engineering, Ministry of Education and Guangdong Province, Shenzhen University, Shenzhen, China
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12
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Wang Z, Qi F, Luo H, Xu G, Wang D. Inflammatory Microenvironment of Skin Wounds. Front Immunol 2022; 13:789274. [PMID: 35300324 PMCID: PMC8920979 DOI: 10.3389/fimmu.2022.789274] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 02/09/2022] [Indexed: 02/06/2023] Open
Abstract
Wound healing is a dynamic and highly regulated process that can be separated into three overlapping and interdependent phases: inflammation, proliferation, and remodelling. This review focuses on the inflammation stage, as it is the key stage of wound healing and plays a vital role in the local immune response and determines the progression of wound healing. Inflammatory cells, the main effector cells of the inflammatory response, have been widely studied, but little attention has been paid to the immunomodulatory effects of wound healing in non-inflammatory cells and the extracellular matrix. In this review, we attempt to deepen our understanding of the wound-healing microenvironment in the inflammatory stage by focusing on the interactions between cells and the extracellular matrix, as well as their role in regulating the immune response during the inflammatory stage. We hope our findings will provide new ideas for promoting tissue regeneration through immune regulation.
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Affiliation(s)
- Zhen Wang
- Department of Plastic Surgery and Burns, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Fang Qi
- Department of Plastic Surgery and Burns, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Han Luo
- Department of Plastic Surgery and Burns, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Guangchao Xu
- Department of Plastic Surgery and Burns, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
| | - Dali Wang
- Department of Plastic Surgery and Burns, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China
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In Vitro and Clinical Evaluation of Cannabigerol (CBG) Produced via Yeast Biosynthesis: A Cannabinoid with a Broad Range of Anti-Inflammatory and Skin Health-Boosting Properties. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27020491. [PMID: 35056807 PMCID: PMC8778347 DOI: 10.3390/molecules27020491] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/06/2022] [Accepted: 01/10/2022] [Indexed: 12/18/2022]
Abstract
Cannabigerol (CBG) is a minor non-psychoactive cannabinoid present in Cannabis sativa L. (C. sativa) at low levels (<1% per dry weight) that serves as the direct precursor to both cannabidiol (CBD) and tetrahydrocannabinol (THC). Consequently, efforts to extract and purify CBG from C. sativa is both challenging and expensive. However, utilizing a novel yeast fermentation technology platform, minor cannabinoids such as CBG can be produced in a more sustainable, cost-effective, and timely process as compared to plant-based production. While CBD has been studied extensively, demonstrating several beneficial skin properties, there are a paucity of studies characterizing the activity of CBG in human skin. Therefore, our aim was to characterize and compare the in vitro activity profile of non-psychoactive CBG and CBD in skin and be the first group to test CBG clinically on human skin. Gene microarray analysis conducted using 3D human skin equivalents demonstrates that CBG regulates more genes than CBD, including several key skin targets. Human dermal fibroblasts (HDFs) and normal human epidermal keratinocytes (NHEKs) were exposed in culture to pro-inflammatory inducers to trigger cytokine production and oxidative stress. Results demonstrate that CBG and CBD reduce reactive oxygen species levels in HDFs better than vitamin C. Moreover, CBG inhibits pro-inflammatory cytokine (Interleukin-1β, -6, -8, tumor necrosis factor α) release from several inflammatory inducers, such as ultraviolet A (UVA), ultraviolet B (UVB), chemical, C. acnes, and in several instances does so more potently than CBD. A 20-subject vehicle-controlled clinical study was performed with 0.1% CBG serum and placebo applied topically for 2 weeks after sodium lauryl sulfate (SLS)-induced irritation. CBG serum showed statistically significant improvement above placebo for transepidermal water loss (TEWL) and reduction in the appearance of redness. Altogether, CBG’s broad range of in vitro and clinical skin health-promoting activities demonstrates its strong potential as a safe, effective ingredient for topical use and suggests there are areas where it may be more effective than CBD.
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Bacterially Delivered miRNA-Mediated Toll-like Receptor 8 Gene Silencing for Combined Therapy in a Murine Model of Atopic Dermatitis: Therapeutic Effect of miRTLR8 in AD. Microorganisms 2021; 9:microorganisms9081715. [PMID: 34442794 PMCID: PMC8401271 DOI: 10.3390/microorganisms9081715] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/17/2021] [Accepted: 07/20/2021] [Indexed: 11/22/2022] Open
Abstract
In atopic dermatitis (AD), skin inflammation is caused by complex interactions between genetic disposition and aberrant innate/adaptive immune responses. Toll-like receptors (TLRs) are key molecules in the innate/adaptive immune response as they recognize various molecular motifs associated with pathogens. Among them, TLR8 is implicated in eczematous skin reactions. We investigated the combined therapeutic effects of TLR8 gene silencing by the bacterial delivery of miRNA. We used Salmonella as a vector to deliver TLR8 miRNA. The recombinant strain of Salmonella enterica subsp. enterica serovar Typhimurium (ST) expressing TLR8 miRNA (ST-miRTLR8) was prepared for knockdown of TLR8. After oral administration of ST-miRTLR8 into mice, we observed the cytokine levels, skin pathology and scratching behaviors in an AD-like mouse model. TLR8 down-regulation decreased macrophage-derived chemokine concentrations in activated human mast cells. Serum IgE and interleukin-4 production were suppressed whereas IFN-γ was induced after oral administration of ST-miRTLR8. Scratching behaviors and skin inflammation were also improved. In addition, attenuated S. typhimurium safely accumulated in mouse macrophages and showed adjuvant effects. This study shows that the recombinant miRNA that expresses the TLR8 miRNA has therapeutic effects by suppressing Th2 inflammation. TLR gene modulation using miRNA via Salmonella vectors will thus have a double-protective effect in the treatment of AD.
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