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Dermatology and Therapy May 2024A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially...
INTRODUCTION
A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data.
METHODS
In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated.
RESULTS
At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12.
CONCLUSIONS
The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT04214639 and NCT04214652.
PubMed: 38724841
DOI: 10.1007/s13555-024-01155-7 -
Case Reports in Dermatology 2021We report on a 69-year-old man who presented with itching and erythematous papules on his torso and extremities, which were resistant to topical therapy with antibiotics...
We report on a 69-year-old man who presented with itching and erythematous papules on his torso and extremities, which were resistant to topical therapy with antibiotics and steroids. Physical examination revealed multiple erythematous papules on his back, neckline, and lower extremities. The lesions had appeared 4 years earlier and usually worsened with heat or extensive sweating. Histopathology of previous skin biopsies had shown multiple cutaneous squamous cell carcinomas or was non-conclusive. Thus, a re-biopsy was performed, revealing acanthosis and focal acantholytic dyskeratosis. These clinical and anamnestic findings lead to the diagnosis of extensive Grover's disease (GD). Oral therapy with isotretinoin 30-mg QD led to the regression of the skin lesions. Topical adapalene, as well as topical corticosteroids, were later prescribed for maintenance therapy.
PubMed: 35082618
DOI: 10.1159/000519168 -
ACS Catalysis Jan 2024Catalyst-controlled C-H functionalization using donor/acceptor carbenes has been shown to be an efficient process capable of high levels of site control and...
Catalyst-controlled C-H functionalization using donor/acceptor carbenes has been shown to be an efficient process capable of high levels of site control and stereocontrol. This study demonstrated that the scope of the donor/acceptor carbene C-H functionalization can be extended to systems where the acceptor group is a phosphonate. When using the optimized dirhodium catalyst, Rh(-(4-Br)TPPTTL), ((aryl)(diazo)methyl)phosphonates undergo highly enantioselective (84-99% ee) and site-selective (>30:1 r.r.) benzylic C-H functionalization. The phosphonate group is much more sterically demanding than the previously studied carboxylate ester group, leading to much higher selectivity for a primary site versus more sterically crowded positions. The effectiveness of this methodology has been demonstrated by the late-stage primary C-H functionalization of estrone, adapalene, ()-naproxen, clofibrate, and gemfibrozil derivatives.
PubMed: 38205024
DOI: 10.1021/acscatal.3c04661 -
Frontiers in Bioengineering and... 2020Dysregulation of the retinoic acid (RA) signaling pathway is observed in amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Here, we investigated...
Dysregulation of the retinoic acid (RA) signaling pathway is observed in amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Here, we investigated the therapeutic potential of retinoid activation via the RA receptor β (RARβ) in the SOD1 mouse model of ALS. Our approach utilized the RARβ agonist adapalene, which we previously found to be neuroprotective Adapalene, like most retinoids, is poorly water soluble, which has thus far prevented effective drug delivery . To address this challenge, we encapsulated adapalene within nanoparticles (Adap-NPs) composed of poly(lactic acid)-poly(ethylene glycol) (PLA-PEG). Our data demonstrate that intravenous administration of Adap-NPs robustly activates retinoid signaling in the CNS. Chronic administration of Adap-NPs resulted in improved motor performance, prolonged lifespan, and neuroprotection in SOD1 mice. This study highlights retinoid signaling as a valuable therapeutic approach and presents a novel nanoparticle platform for the treatment of ALS.
PubMed: 32292776
DOI: 10.3389/fbioe.2020.00224 -
Cells Nov 2019Ventricular arrhythmias (VA) are a common cause of sudden death after myocardial infarction (MI). Therefore, developing new therapeutic methods for the prevention and...
BACKGROUND
Ventricular arrhythmias (VA) are a common cause of sudden death after myocardial infarction (MI). Therefore, developing new therapeutic methods for the prevention and treatment of VA is of prime importance.
METHODS
Human bone marrow derived CD271 mesenchymal stem cells (MSC) were tested for their antiarrhythmic effect. This was done through the development of a novel mouse model using an immunocompromised Rag2 γc mouse strain subjected to myocardial "infarction-reinfarction". The mice underwent a first ischemia-reperfusion through the left anterior descending (LAD) artery closure for 45 minutes with a subsequent second permanent LAD ligation after seven days from the first infarct.
RESULTS
This mouse model induced various types of VA detected with continuous electrocardiogram (ECG) monitoring via implanted telemetry device. The immediate intramyocardial delivery of CD271 MSC after the first MI significantly reduced VA induced after the second MI.
CONCLUSIONS
In addition to the clinical relevance, more closely reflecting patients who suffer from severe ischemic heart disease and related arrhythmias, our new mouse model bearing reinfarction warrants the time required for stem cell engraftment and for the first time enables us to analyze and verify significant antiarrhythmic effects of human CD271 stem cells in vivo.
Topics: Adapalene; Animals; Anti-Arrhythmia Agents; Disease Models, Animal; Female; Humans; Immunophenotyping; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Knockout; Myocardial Infarction
PubMed: 31757119
DOI: 10.3390/cells8121474 -
Biomaterials Jan 2022In the strategy of in situ bone regeneration, it used to be difficult to specifically recruit bone marrow mesenchymal stem cells (BM-MSCs) by a single marker. Recently,...
In the strategy of in situ bone regeneration, it used to be difficult to specifically recruit bone marrow mesenchymal stem cells (BM-MSCs) by a single marker. Recently, CD271 has been considered to be one of the most specific markers to isolate BM-MSCs; however, the effectiveness of CD271 antibodies in recruiting BM-MSCs has not been explored yet. In this study, we developed novel CD271 antibody-functionalized chitosan (CS) microspheres with the aid of polydopamine (PDA) coating to recruit endogenous BM-MSCs for in situ bone regeneration. The CS microspheres were sequentially modified with PDA and CD271 antibody through dopamine self-polymerization and bioconjugation, respectively. In vitro studies showed that the CD271 antibody-functionalized microspheres selectively captured significantly more BM-MSCs from a fluorescently labeled heterotypic cell population than non-functionalized controls. In addition, the PDA coating was critical for supporting stable adhesion and proliferation of the captured BM-MSCs. Effective early recruitment of CD271 stem cells by the functionalized microspheres at bone defect site of SD rat was observed by the CD271/DAPI immunofluorescence staining, which led to significantly enhanced new bone formation in rat femoral condyle defect over long term. Together, findings from this study have demonstrated, for the first time, that the CD271 antibody-functionalized CS microspheres are promising for in situ bone regeneration.
Topics: Adapalene; Animals; Bone Marrow Cells; Bone Regeneration; Cell Differentiation; Microspheres; Rats; Rats, Sprague-Dawley; Stem Cells
PubMed: 34838337
DOI: 10.1016/j.biomaterials.2021.121243 -
Molecules (Basel, Switzerland) Sep 2021Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative...
Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes' pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (, and ). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-β/collagen, Wnt/β-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.
Topics: Acne Vulgaris; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Behavior, Animal; Biofilms; Cues; Forkhead Transcription Factors; Insulin-Like Growth Factor I; Interleukin-6; NF-kappa B; Nanogels; PPAR gamma; Plant Extracts; Polyethylene Glycols; Polyethyleneimine; Rats; Skin; Syzygium; Thymus Plant; Toll-Like Receptor 2; Transforming Growth Factor beta; Wnt Proteins
PubMed: 34577079
DOI: 10.3390/molecules26185608 -
Cells Dec 2019Bone marrow (BM)-derived stem cells with their various functions and characteristics have become a well-recognized source for the cell-based therapies. However,...
BACKGROUND
Bone marrow (BM)-derived stem cells with their various functions and characteristics have become a well-recognized source for the cell-based therapies. However, knowledge on their therapeutic potential and the shortage for a cross-link between distinct BM-derived stem cells, primed after the onset of myocardial infarction (MI), seems to be still rudimentary. Therefore, the post-examination of the therapeutic characteristics of such primed hematopoietic CD133 and mesenchymal CD271 stem cells was the object of the present study.
METHODS AND RESULTS
The effects of respective CD133 and CD271 mononuclear cells alone as well as in the co-culture model have been explored with focus on their angiogenic potential. The phenotypic analysis revealed a small percentage of isolated cells expressing both surface markers. Moreover, target stem cells isolated with our standardized immunomagnetic isolation procedure did not show any negative alterations following BM storage in regard to cell numbers and/or quality. In vitro network formation relied predominantly on CD271 stem cells when compared with single CD133 culture. Interestingly, CD133 cells contributed in the tube formation, only if they were cultivated in combination with CD271 cells. Additional to the in vitro examination, therapeutic effects of the primed stem cells were investigated 48 h post MI in a murine model. Hence, we have found a lower expression of transforming growth factor βeta 3 (TGFβ3) as well as an increase of the proangiogenic factors after CD133 cell treatment in contrast to CD271 cell treatment. On the other hand, the CD271 cell therapy led to a lower expression of the inflammatory cytokines.
CONCLUSION
The interactions between CD271 and CD133 subpopulations the extent to which the combination may enhance cardiac regeneration has still not been investigated so far. We expect that the multiple characteristics and various regenerative effects of CD271 cells alone as well as in combination with CD133 will result in an improved therapeutic impact on ischemic heart disease.
Topics: AC133 Antigen; Adapalene; Animals; Biomarkers; Bone Marrow Cells; Cell Differentiation; Cell Proliferation; Disease Models, Animal; Female; Fluorescent Antibody Technique; Gene Expression Profiling; Immunophenotyping; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Transgenic; Myocardial Infarction; Neovascularization, Physiologic; Regeneration
PubMed: 31892273
DOI: 10.3390/cells9010078 -
BioMed Research International 2020Many topical agents are available for treating the acute phase of acne; however, few agents have been proven beneficial during the maintenance phase. To evaluate the... (Randomized Controlled Trial)
Randomized Controlled Trial
A Double-Blinded, Randomized, Vehicle-Controlled Study of the Efficacy of Moisturizer Containing Licochalcone A, Decanediol, L-Carnitine, and Salicylic Acid for Prevention of Acne Relapse in Asian Population.
Many topical agents are available for treating the acute phase of acne; however, few agents have been proven beneficial during the maintenance phase. To evaluate the efficacy and safety of moisturizer containing licochalcone A, 1,2-decanediol, L-carnitine, and salicylic acid during the maintenance phase of mild to moderate acne in Thai patients. One hundred and ten patients with mild to moderate acne vulgaris were initially treated with a fixed combination of adapalene 0.1%/benzoyl peroxide 2.5% gel once daily for 8 weeks. Fifty patients who achieved at least 50% reduction in lesion counts or at least a 2-grade improvement in the Investigator's Global Assessment (IGA) grade from baseline were enrolled in the maintenance phase, which was an investigator-masked, left-right comparison, randomized, controlled, intraindividual study. Moisturizers with and without the active study ingredients were applied twice a day to each side of the face, respectively, for 12 weeks. Assessments included acne lesion counts, acne severity by IGA scoring, skin bioengineering measurements, and skin tolerability as assessed by both patient and physician. The treatment group had a significant reduction in the mean counts of noninflammatory, inflammatory, and total lesions compared to the vehicle group at week 12 and also between baseline and week 12. There was no significant difference in the mean scores for skin dryness, stinging/burning, or pruritus at any time point between groups. Moisturizer containing licochalcone A, 1,2-decanediol, L-carnitine, and salicylic acid reduced acne lesions and prevented the development of new lesions during the maintenance phase. This trial is registered with ClinicalTrials.gov registration no. NCT04002024.
Topics: Acne Vulgaris; Administration, Cutaneous; Adolescent; Anti-Inflammatory Agents; Asian People; Carnitine; Chalcones; Dermatologic Agents; Double-Blind Method; Drug Therapy, Combination; Face; Female; Gels; Glycols; Humans; Male; Salicylic Acid; Severity of Illness Index; Skin; Treatment Outcome
PubMed: 33150170
DOI: 10.1155/2020/2857812 -
Upsala Journal of Medical Sciences Nov 2019Murine boundary cap-derived neural crest stem cells (NCSCs) are capable of enhancing islet function by stimulating beta cell proliferation as well as increasing the...
Murine boundary cap-derived neural crest stem cells (NCSCs) are capable of enhancing islet function by stimulating beta cell proliferation as well as increasing the neural and vascular density in the islets both and . This study aimed to isolate NCSC-like cells from human bone marrow. CD271 magnetic cell separation and culture techniques were used to purify a NCSC-enriched population of human bone marrow. Analyses of the CD271+ and CD271- fractions in terms of protein expression were performed, and the capacity of the CD271+ bone marrow cells to form 3-dimensional spheres when grown under non-adherent conditions was also investigated. Moreover, the NCSC characteristics of the CD271+ cells were evaluated by their ability to migrate toward human islets as well as human islet-like cell clusters (ICC) derived from pluripotent stem cells. The CD271+ bone marrow population fulfilled the criterion of being multipotent stem cells, having the potential to differentiate into glial cells, neurons as well as myofibroblasts . They had the capacity to form 3-dimensional spheres as well as an ability to migrate toward human islets, further supporting their NCSC identity. Additionally, we demonstrated similar migration features toward stem cell-derived ICC. The results support the NCSC identity of the CD271-enriched human bone marrow population. It remains to investigate whether the human bone marrow-derived NCSCs have the ability to improve transplantation efficacy of not only human islets but stem cell-derived ICC as well.
Topics: Adapalene; Adult; Aged; Bone Marrow Cells; Cell Culture Techniques; Cell Differentiation; Cell Movement; Cell Proliferation; Cell Separation; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Middle Aged; Neural Crest; Pluripotent Stem Cells; Young Adult
PubMed: 31623497
DOI: 10.1080/03009734.2019.1658661