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Theranostics 2024Spinal cord injury (SCI) results in neural tissue damage. However, the limited regenerative capacity of adult mammals' axons upon SCI leads to persistent neurological...
Exosomes derived from CD271CD56 bone marrow mesenchymal stem cell subpopoulation identified by single-cell RNA sequencing promote axon regeneration after spinal cord injury.
Spinal cord injury (SCI) results in neural tissue damage. However, the limited regenerative capacity of adult mammals' axons upon SCI leads to persistent neurological dysfunction. Thus, exploring the pathways that can enhance axon regeneration in injured spinal cord is of great significance. Through the utilization of single-cell RNA sequencing in this research, a distinct subpopulation of bone marrow mesenchymal stem cells (BMSCs) that exhibits the capacity to facilitate axon regeneration has been discovered. Subsequently, the CD271CD56 BMSCs subpopulation was isolated using flow cytometry, and the exosomes derived from this subpopulation (CD271CD56 BMSC-Exos) were extracted and incorporated into a hydrogel to create a sustained release system. The aim was to investigate the therapeutic effects of CD271CD56 BMSC-Exos and elucidate the underlying mechanisms involved in promoting axon regeneration and neural function recovery. The findings indicate that CD271CD56 BMSC-Exos share similar physical and chemical properties with conventional exosomes. Importantly, in an SCI model, in situ implantation of CD271CD56 BMSC-Exos hydrogel resulted in increased expression of NF and synaptophysin, markers associated with axon regeneration and synapse formation, respectively. This intervention also contributed to improved neural function recovery. In vitro experiments demonstrated that CD271CD56 BMSC-Exos treatment significantly enhanced axon extension distance and increased the number of branches in dorsal root ganglion axons. Moreover, further investigation into the molecular mechanisms underlying CD271CD56 BMSC-Exos-mediated axon regeneration revealed the crucial involvement of the miR-431-3p/RGMA axis. In summary, the implantation of CD271CD56 BMSC-Exos hydrogel presents a promising and effective therapeutic approach for SCI.
Topics: Adult; Animals; Humans; Axons; Exosomes; Adapalene; Nerve Regeneration; Mesenchymal Stem Cells; Spinal Cord Injuries; Hydrogels; Sequence Analysis, RNA; Mammals
PubMed: 38169566
DOI: 10.7150/thno.89008 -
ACS Applied Bio Materials Sep 2023There is an urgent need for simple and non-invasive identification of live neural stem/progenitor cells (NSPCs) in the developing and adult brain as well as in disease,...
There is an urgent need for simple and non-invasive identification of live neural stem/progenitor cells (NSPCs) in the developing and adult brain as well as in disease, such as in brain tumors, due to the potential clinical importance in prognosis, diagnosis, and treatment of diseases of the nervous system. Here, we report a luminescent conjugated oligothiophene (LCO), named p-HTMI, for non-invasive and non-amplified real-time detection of live human patient-derived glioblastoma (GBM) stem cell-like cells and NSPCs. While p-HTMI stained only a small fraction of other cell types investigated, the mere addition of p-HTMI to the cell culture resulted in efficient detection of NSPCs or GBM cells from rodents and humans within minutes. p-HTMI is functionalized with a methylated imidazole moiety resembling the side chain of histidine/histamine, and non-methylated analogues were not functional. Cell sorting experiments of human GBM cells demonstrated that p-HTMI labeled the same cell population as CD271, a proposed marker for stem cell-like cells and rapidly migrating cells in glioblastoma. Our results suggest that the LCO p-HTMI is a versatile tool for immediate and selective detection of neural and glioma stem and progenitor cells.
Topics: Adult; Humans; Glioblastoma; Brain; Brain Neoplasms; Neural Stem Cells; Adapalene
PubMed: 37647213
DOI: 10.1021/acsabm.3c00447 -
Cutis Aug 2023A range of treatment options are available for both mild to moderate and moderate to severe acne, and these options vary widely in their clinical uses, effectiveness,... (Review)
Review
A range of treatment options are available for both mild to moderate and moderate to severe acne, and these options vary widely in their clinical uses, effectiveness, and costs. With the continued rise of dermatologic drug prices and increased cost-sharing due to high-deductible health plans, the importance of cost-effective treatment continues to grow. Failure to consider cost-effective, patient-centered care may lead to increased financial toxicity, reduced adherence, and ultimately worse outcomes and patient satisfaction. Combination topical products offer improved efficacy and convenience, which are associated with better adherence and outcomes. Generic fixed-dose adapalene-benzoyl peroxide (BPO) and fixed-dose clindamycin-BPO can be highly cost-effective options for patients with mild to moderate acne. Hormonal agents such as combined oral contraceptives (COCs) and spironolactone are inexpensive and likely reflect a highly cost-effective option that could reduce reliance on oral antibiotics in patients with moderate to severe acne. Doxycycline and isotretinoin also are cost-effective options for more severe acne. Frequent laboratory monitoring for spironolactone and isotretinoin continues to be prevalent despite little evidence to support its clinical utility, and it is associated with a major cost burden to the patient and health care system. The reduction of laboratory monitoring is an opportunity to provide higher-value care.
Topics: Humans; Dermatologic Agents; Benzoyl Peroxide; Isotretinoin; Adapalene; Cost-Benefit Analysis; Spironolactone; Drug Combinations; Acne Vulgaris; Treatment Outcome; Gels
PubMed: 37820334
DOI: 10.12788/cutis.0844 -
Cureus Apr 2024Acne vulgaris, commonly called acne, is a skin condition affecting many individuals globally. It is a chronic condition characterized by developing pimples, blackheads... (Review)
Review
Acne vulgaris, commonly called acne, is a skin condition affecting many individuals globally. It is a chronic condition characterized by developing pimples, blackheads (open comedones), whiteheads (closed comedones), and other skin lesions. Acne usually appears on the face, neck, chest, and back. It is commonly associated with puberty and adolescence but can also affect adults of all ages. Acne can be very frustrating and embarrassing, leading to low self-esteem and social isolation. The condition arises from various factors, including clogged pores, excessive sebum production, bacteria, and inflammation. This systematic review assesses the effectiveness of topical antibiotics, retinoids, niacinamide, azelaic acid, and clascoterone in treating mild-to-moderate acne vulgaris. A comprehensive search across PubMed, PubMed Central, and Google Scholar yielded 10 articles focused on topical antibiotics, with findings from 198 subjects indicating the efficacy of doxycycline against inflammatory lesions. Retinoids, such as tretinoin and adapalene, significantly improved both lesion types (open and closed comedones). Niacinamide, examined in a randomized controlled trial involving 41 participants, reduced sebum production. Another study with 60 patients revealed that azelaic acid effectively reduced both inflammatory and non-inflammatory lesions. Clascoterone emerged as a promising antiandrogenic treatment, supported by a randomized controlled trial involving 4,440 patients. It is essential that individualized therapy, incorporating patient preferences and considering adverse effects, is emphasized for optimizing acne management.
PubMed: 38725769
DOI: 10.7759/cureus.57909 -
Pharmaceuticals (Basel, Switzerland) Aug 2020Adapalene (ADP) is a representative of the third retinoids generation and successfully used in first-line acne treatment. ADP binds to retinoic acid nuclear receptors.... (Review)
Review
Adapalene (ADP) is a representative of the third retinoids generation and successfully used in first-line acne treatment. ADP binds to retinoic acid nuclear receptors. The comedolytic, anti-inflammatory, antiproliferative, and immunomodulatory are the known ADP effects. Its safety profile is an advantage over other retinoids. ADP recently was found to be effective in the treatment of several dermatological diseases and photoaging besides the utility in the treatment of acne vulgaris. New biological effects of adapalene with therapeutic potential are highlighted in this review paper. Thus, adapalene could be a valuable therapeutic drug into the treatment of several types of cancer. Additionally, some neurodegenerative diseases could be treated with a suitable formulation for intravenous administration. The antibacterial activity against methicillin-resistant of an analogue of ADP has been proven. In different therapeutic schemes, ADP is more effective in combination with other active substances. New topical combinations with adapalene include ketoconazole (antifungal), mometasone furoate (anti-inflammatory corticosteroid), nadifloxacin (fluoroquinolone), and alfa and beta hydroxy acids. Combination with oral drugs is a new trend that enhances the properties of topical formulations with adapalene. Several studies have investigated the effects of ADP in co-administration with azithromycin, doxycycline, faropenem, isotretinoin, and valganciclovir. Innovative formulations of ADP also aim to achieve a better bioavailability, increased efficacy, and reduced side effects. In this review, we have highlighted the current studies on adapalene regarding biological effects useful in various treatment types. Adapalene has not been exploited yet to its full biological potential.
PubMed: 32872149
DOI: 10.3390/ph13090217 -
Gels (Basel, Switzerland) Feb 2023Retinoids are considered the mainstay treatment for moderate to severe acne. Adapalene, a third-generation retinoid, has physiochemical properties which hinder the...
Retinoids are considered the mainstay treatment for moderate to severe acne. Adapalene, a third-generation retinoid, has physiochemical properties which hinder the effective delivery of the drug to the skin. Therefore, the current study aimed to develop and evaluate adapalene liposomal loaded gel (ADA-LP gel) for the effective management of acne to improve tolerability and delivery to targeted sites as compared to the conventional dosage form of the drug. A novel spontaneous phase transition method (SPT) was used to formulate liposomes. Liposomal formulation (ADA-LP) was prepared and optimized based on particle size, zeta potential, and PDI. Optimized formulation was further characterized by different techniques and loaded into Carbopol gel. In vitro drug release, ex vivo permeation, and in vivo studies were performed using the prepared adapalene-loaded liposomal-based gel. The in vivo study was done employing the testosterone-induced acne model in mice. The optimized formulation had a size of 181 nm, PDI 0.145, and a zeta potential of -35 mV, indicating that the formulation was stable. Encapsulation efficiency was 89.69 ± 0.5%. ADA-LPs were loaded into the gel. Prepared ADA-LP showed a 79 ± 0.02% release of drug in a sustained manner, within 24 h. The ex vivo permeability study showed a total of 43 ± 0.06 µg/cm of drug able to permeate through the skin within 24 h. Moreover, only 28.27 ± 0.04% was retained on the epidermis. The developed ADA-LP gel showed significant improvement in the acne lesions in mice with no visible scars and inflammation on the skin. Therefore, ADA-LP-based gel could be a promising carrier system for the safe and effective delivery of Adapalene.
PubMed: 36826305
DOI: 10.3390/gels9020135 -
The Journal of Dermatological Treatment Dec 2023Using a three-pronged acne treatment approach-combining an antibiotic, antimicrobial agent, and retinoid-may provide greater efficacy than monad or dyad treatments.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Using a three-pronged acne treatment approach-combining an antibiotic, antimicrobial agent, and retinoid-may provide greater efficacy than monad or dyad treatments. Herein are the dermal sensitization, irritation, safety, and tolerability results from phase 1 and 2 studies of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) polymeric mesh gel.
METHODS
Two phases 1, single-blind, vehicle-controlled dermal safety studies were conducted in healthy participants aged ≥18 years. One phase 2 (NCT03170388) double-blind, randomized, parallel-group, and vehicle-controlled study was conducted over 12 weeks in participants aged ≥9 years with moderate-to-severe acne.
RESULTS
A total of 1,020 participants (IDP-126 gel, vehicle, or 1 of the 3 dyad gels [phase 2 only]) were included across the 3 studies (safety populations: = 1,004). In the phase 1 studies, IDP-126 had no confirmed sensitization or contact dermatitis. IDP-126 (deemed "moderately irritating") was significantly less irritating than commercially available BPO 2.5%/adapalene 0.3% gel.
CONCLUSIONS
The results from these three studies show that the triple-combination IDP-126 had a positive safety profile and was well tolerated in healthy participants and those with moderate-to-severe acne.
Topics: Humans; Adolescent; Adult; Adapalene; Peroxides; Single-Blind Method; Benzoyl Peroxide; Acne Vulgaris
PubMed: 37341243
DOI: 10.1080/09546634.2023.2220446 -
Pharmaceutics Aug 2022Photodynamic therapy (PDT) is a highly effective and widely adopted treatment strategy for many skin diseases, particularly for multiple actinic keratoses (AKs).... (Review)
Review
Photodynamic therapy (PDT) is a highly effective and widely adopted treatment strategy for many skin diseases, particularly for multiple actinic keratoses (AKs). However, PDT is ineffective in some cases, especially if AKs occur in the acral part of the body. Several methods to improve the efficacy of PDT without significantly increasing the risks of side effects have been proposed. In this study, we reviewed the combination-based PDT treatments described in the literature for treating AKs; both post-treatment and pretreatment were considered including topical (i.e., diclofenac, imiquimod, adapalene, 5-fluorouracil, and calcitriol), systemic (i.e., acitretin, methotrexate, and polypodium leucotomos), and mechanical-physical (i.e., radiofrequency, thermomechanical fractional injury, microneedling, microdermabrasion, and laser) treatment strategies. Topical pretreatments with imiquimod, adapalene, 5-fluorouracil, and calcipotriol were more successful than PDT alone in treating AKs, while the effect of diclofenac gel was less clear. Both mechanical laser treatment with CO and Er:YAG (Erbium:Yttrium-Aluminum-Garnet) as well as systemic treatment with Polypodium leucotomos were also effective. Different approaches were relatively more effective in particular situations such as in immunosuppressed patients, AKs in the extremities, or thicker AKs. Conclusions: Several studies showed that a combination-based approach enhanced the effectiveness of PDT. However, more studies are needed to further understand the effectiveness of combination therapy in clinical practice and to investigate the role of acitretin, methotrexate, vitamin D, thermomechanical fractional injury, and microdermabrasion in humans.
PubMed: 36015352
DOI: 10.3390/pharmaceutics14081726 -
Molecular Diversity Feb 2023Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classified as "variant of concern" due to their increased transmissibility and better viral fitness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous variants of concern, the Omicron variant has 15 mutations on the receptor-binding domain of spike protein and the changes in the key amino acid residues of S protein can enhance the binding ability of the virus to hACE2, resulting in a significant increase in the infectivity of the Omicron variant. Therefore, there is still an urgent need for treatment and prevention of variants of concern, particularly for the Omicron variant. In this study, an in silico drug repurposing was conducted through the molecular docking of 2890 FDA-approved drugs against the mutant S protein of SARS-CoV-2 for Omicron variant. We discovered promising drug candidates for the inhibition of alarming Omicron variant such as quinestrol, adapalene, tamibarotene, and dihydrotachysterol. The stability of ligands complexed with the mutant S protein was confirmed using MD simulations. The lead compounds were further evaluated for their potential use and side effects based on the current literature. Particularly, adapalene, dihydrotachysterol, levocabastine and bexarotene came into prominence due to their non-interference with the normal physiological processes. Therefore, this study suggests that these approved drugs can be considered as drug candidates for further in vitro and in vivo studies to develop new treatment options for the Omicron variant of SARS-CoV-2.
Topics: Humans; Antiviral Agents; SARS-CoV-2; Dihydrotachysterol; Adapalene; COVID-19; Drug Repositioning; Molecular Docking Simulation
PubMed: 35507211
DOI: 10.1007/s11030-022-10440-6 -
Neuromolecular Medicine Sep 2021Traditionally, the primary role of the meninges is thought to be structural, i.e., to act as a surrounding membrane that contains and cushions the brain with... (Review)
Review
Traditionally, the primary role of the meninges is thought to be structural, i.e., to act as a surrounding membrane that contains and cushions the brain with cerebrospinal fluid. During development, the meninges is formed by both mesenchymal and neural crest cells. There is now emerging evidence that subsets of undifferentiated stem cells might persist in the adult meninges. In this mini-review, we survey representative studies of brain-meningeal interactions and discuss the hypothesis that the meninges are not just protective membranes, but instead contain multiplex stem cell subsets that may contribute to central nervous system (CNS) homeostasis. Further investigations into meningeal multipotent cells may reveal a "hidden" target for promoting neurovascular remodeling and repair after CNS injury and disease.
Topics: Adapalene; Adult Stem Cells; Animals; Brain Ischemia; Central Nervous System; Central Nervous System Diseases; Glymphatic System; Homeostasis; Humans; Male; Meninges; Multipotent Stem Cells; Neural Crest; Neural Stem Cells; Rats; Rats, Sprague-Dawley; Regeneration
PubMed: 33893971
DOI: 10.1007/s12017-021-08663-1