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Briefings in Bioinformatics Mar 2024Gliomas are the most common type of malignant brain tumors, with glioblastoma multiforme (GBM) having a median survival of 15 months due to drug resistance and relapse....
Gliomas are the most common type of malignant brain tumors, with glioblastoma multiforme (GBM) having a median survival of 15 months due to drug resistance and relapse. The treatment of gliomas relies on surgery, radiotherapy and chemotherapy. Only 12 anti-brain tumor chemotherapies (AntiBCs), mostly alkylating agents, have been approved so far. Glioma subtype-specific metabolic models were reconstructed to simulate metabolite exchanges, in silico knockouts and the prediction of drug and drug combinations for all three subtypes. The simulations were confronted with literature, high-throughput screenings (HTSs), xenograft and clinical trial data to validate the workflow and further prioritize the drug candidates. The three subtype models accurately displayed different degrees of dependencies toward glutamine and glutamate. Furthermore, 33 single drugs, mainly antimetabolites and TXNRD1-inhibitors, as well as 17 drug combinations were predicted as potential candidates for gliomas. Half of these drug candidates have been previously tested in HTSs. Half of the tested drug candidates reduce proliferation in cell lines and two-thirds in xenografts. Most combinations were predicted to be efficient for all three glioma types. However, eflornithine/rifamycin and cannabidiol/adapalene were predicted specifically for GBM and low-grade glioma, respectively. Most drug candidates had comparable efficiency in preclinical tests, cerebrospinal fluid bioavailability and mode-of-action to AntiBCs. However, fotemustine and valganciclovir alone and eflornithine and celecoxib in combination with AntiBCs improved the survival compared to AntiBCs in two-arms, phase I/II and higher glioma clinical trials. Our work highlights the potential of metabolic modeling in advancing glioma drug discovery, which accurately predicted metabolic vulnerabilities, repurposable drugs and combinations for the glioma subtypes.
Topics: Humans; Glioma; Cannabidiol; Brain Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Animals; Models, Biological; Cell Line, Tumor; Organophosphorus Compounds
PubMed: 38701414
DOI: 10.1093/bib/bbae199 -
International Journal of Dermatology Jun 2024Acne, a highly prevalent skin disease, can be particularly bothersome for patients of Asian background because of its impact on self-confidence and social interactions.... (Review)
Review
Acne, a highly prevalent skin disease, can be particularly bothersome for patients of Asian background because of its impact on self-confidence and social interactions. In addition to active acne lesions, some patients may develop sequelae such as scarring, macular/postinflammatory hyperpigmentation, or erythema. The tendency of Asian skin to develop sequelae because of its increased susceptibility to irritation, cultural preferences for lighter skin phototypes, and differences in skincare regimens may all contribute to the increased burden of acne. Moreover, many Asia-Pacific countries do not have their own guidelines for acne management, and those that do often have no schedule in place for regular updates. In this article, we provide a critical review of the published guidance for the management of acne and its sequelae in the Asia-Pacific region, identifying gaps in current recommendations that could be addressed to enhance standards of acne care in Asia-Pacific countries. Along with highlighting the importance of a comprehensive skincare regimen to increase treatment efficacy and adherence, we discuss topical retinoids and retinoid combination options in the acne armamentarium that may be beneficial for sequelae prevention and management, such as adapalene 0.3% ± benzoyl peroxide 2.5%, tretinoin 0.05%, tazarotene 0.1%, and trifarotene 0.005%. In particular, trifarotene 0.005% has been observed to significantly reduce acne scar counts in a Phase 4 study. The recent data highlight the need to establish up-to-date guidance for acne and acne sequelae management in Asia-Pacific countries to provide optimal care to Asian patients.
Topics: Humans; Acne Vulgaris; Dermatologic Agents; Retinoids; Asia; Hyperpigmentation; Administration, Cutaneous; Cicatrix; Practice Guidelines as Topic; Skin Care; Erythema
PubMed: 38643368
DOI: 10.1111/ijd.17141 -
Journal of Cosmetic Dermatology Jun 2024Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
2% supramolecular salicylic acid hydrogel vs. adapaline gel in mild to moderate acne vulgaris treatment: A multicenter, randomized, evaluator-blind, parallel-controlled trial.
OBJECTIVE
Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of mild to moderate acne, and the improvement of the skin condition by using 2% supramolecular salicylic acid (SSA) compared to Davuwen Adapaline gel.
METHODS
A multicenter, randomized, assessor-blind and parallel-controlled study was conducted. A total of 500 patients (trial group: 249, control group: 251) with mild to moderate (grade I-II) facial acne vulgaris were recruited in this study over a 16-week trial period. Patients in the trial group were treated with Broda 2% SSA hydrogel, while control group treated with Davuwen Adapaline gel once a day. The number of inflammatory papules, comedones, and pustules were counted and the rate of lesion reduction was calculated pre- and post-treatment. Then, the skin physiological indicators, including L*a*b*, TEWL, skin sebum and hydration were measured. Statistical analysis was conducted using SAS 9.4. Significance was set at p = 0.05.
RESULTS
At the end of 12 weeks' therapy, the regression and markedly improvement rate of the trail group and the control group were 51.01% and 43.10% respectively, and there was no significant difference in the improvement rate between two groups (p = 0.0831). Although, there was no difference in adverse events rate between two groups, the adverse events rate of the trail group was 0.40%, a little lower than the control group (0.80%). Moreover, there was a significant difference in the numbers of pores at T1 between two groups.
CONCLUSION
Both 2% SSA and Adapaline gel were equally effective in the treatment of mild to moderate acne vulgaris. 2% SSA is worth the clinical promotion and application in mild to moderate acne vulgaris.
Topics: Humans; Acne Vulgaris; Female; Male; Salicylic Acid; Young Adult; Adolescent; Severity of Illness Index; Adult; Single-Blind Method; Gels; Hydrogels; Treatment Outcome; Dermatologic Agents; Administration, Cutaneous; Adapalene
PubMed: 38590107
DOI: 10.1111/jocd.16238 -
Cureus Mar 2024Introduction Acne vulgaris is one of the most common skin problems encountered in the dermatology department. It is a chronic, inflammatory disease of the pilosebaceous...
Introduction Acne vulgaris is one of the most common skin problems encountered in the dermatology department. It is a chronic, inflammatory disease of the pilosebaceous unit, clinically presenting with comedones, papules, pustules, nodules, and cysts. With its particularly high prevalence in the younger population, it has significant adverse sequelae on patient's quality of life. At present, due to an enhanced understanding of the pathogenesis of acne, various therapeutic modalities are available. The current management strategies generally follow a systematic treatment escalation based on disease severity and treatment response. However meticulous choice of appropriate anti-acne medicine for the acne type is the key to the management plan. Starting with mild to moderate types of acne as per the Leeds photometric grading scale, the most useful topical agents include topical retinoids, benzoyl peroxide, and topical antibiotics while systemic therapies such as oral antibiotics or isotretinoin are generally reserved for moderate to severe acne treatment. The skin of color (SOC) population is a relatively neglected group concerning the optimum and safe management strategies in different dermatological conditions and acne is no different, where there remains a need for comparing the available topical modalities for appropriate drug selection in the treatment of mild to moderate acne in SOC population. Objective The objective of this study was to compare the efficacy of topical 4% benzoyl peroxide versus topical 0.1% adapalene in the treatment of acne vulgaris in the SOC population. Methods The participants were divided into two groups, groups A and B. A total of 64 patients of both genders, with acne vulgaris (duration > three months) were included in the study. In group A, 32 patients were administered topical 0.1% adapalene whereas, in group B, 32 patients were given topical 4% benzoyl peroxide. Both medicines were applied at night daily. Patients were called for follow-up after 12 weeks. In both groups, the final efficacy evaluation was done using the Global Acne Grading System (GAGS) score after 12 weeks of treatment period. Results In group A, the age ranged from 15 to 40 years with a mean age of 25.781±3.93 years while the duration of complaint was 5.843±1.27 months. GAGS score was 25.281±2.65 and mean BMI was 23.092±3.51 kg/m2. In group B, the mean age was 25.187± 4.06 years, the duration of complaint was 7.375±2.25 months, the GAGS score was 23.906± 2.60 while the mean BMI was 21.485±3.88 kg/m2. Efficacy in group A was noted in 25 (78.1%) patients as compared to 24 (75%) patients in group B (p =0.768). Conclusion The present study showed that the safety and efficacy of 0.1% adapalene the traditional drug 4% benzoyl peroxide in the SOC population was comparable.
PubMed: 38576696
DOI: 10.7759/cureus.55555 -
The Medical Letter on Drugs and... Apr 2024
Topics: Humans; Acne Vulgaris; Dermatologic Agents; Gels; Adapalene; Benzoyl Peroxide; Drug Combinations; Clindamycin
PubMed: 38576148
DOI: 10.58347/tml.2024.1700b -
Journal of Drugs in Dermatology : JDD Apr 2024Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne treatments has not been systematically examined.
METHODS
A systematic literature review (SLR) was conducted to identify randomized controlled trials of ≥4 weeks of treatment (topical, oral, physical, or combinations) for moderate-to-severe facial acne in patients aged ≥9 years. Efficacy outcomes included: percentage of patients achieving ≥2-grade reduction from baseline and “clear” or “almost clear” for global severity score (treatment success); absolute change in inflammatory (ILs reduction); and noninflammatory lesion counts (NILs reduction). A random-effects network meta-analysis (NMA) was conducted for the efficacy outcomes. Treatments were ranked with posterior rank plots and surface under cumulative ranking values. Results: Eighty-five studies were included in the SLR/NMA. Topical triple-agent fixed-dose combination (FDC) gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments with oral antibiotics (TOA3) consistently ranked in the top 3 treatments. Topical triple-agent FDC gel was numerically superior to TOA3 for treatment success (log-odds ratios: 1.84 [95% credible interval (CrI) 1.36 to 2.29]) and 1.69 (95% CrI: 1.01 to 2.32) vs placebo/vehicle). TOA3 was numerically superior to topical triple-agent FDC gel for reduction of ILs (mean difference: -8.21 [-10.33 to -6.13]) and -10.40 [-13.44 to -7.14] vs placebo/vehicle) and NILs (mean difference: -13.41 [-16.69 to -10.32] and -17.74 [-22.56 to -12.85] vs placebo/vehicle).
CONCLUSIONS
Based on this SLR/NMA, topical triple-agent FDC gel was the most efficacious and safe treatment for moderate-to-severe acne. J Drugs Dermatol. 2024;23(4): doi:10.36849/JDD.8148.
Topics: Humans; Dermatologic Agents; Benzoyl Peroxide; Acne Vulgaris; Network Meta-Analysis; Drug Combinations; Adapalene, Benzoyl Peroxide Drug Combination; Treatment Outcome; Gels
PubMed: 38564399
DOI: 10.36849/JDD.8148 -
Zhongguo Dang Dai Er Ke Za Zhi =... Mar 2024To investigate the effects of different concentrations of adapalene on the morphology and functions of neuroblastoma cell line SH-SY5Y, as well as its role in inducing...
OBJECTIVES
To investigate the effects of different concentrations of adapalene on the morphology and functions of neuroblastoma cell line SH-SY5Y, as well as its role in inducing cell differentiation and apoptosis.
METHODS
SH-SY5Y cells were divided into control group, low concentration (0.1 μM and 1 μM) adapalene groups, and high concentration (10 μM) adapalene group. Time-lapse microscopy was used to observe the morphological changes of SH-SY5Y cells. Immunofluorescence staining was performed to detect the expression of neuronal specific marker βIII-tubulin and mature neuronal marker neurofilament heavy polypeptide (NFH). Multi-electrode array was used to record the electrophysiological features of SH-SY5Y cells. Cell apoptosis was evaluated using a cell apoptosis detection kit.
RESULTS
Low concentrations of adapalene promoted the formation of neurite outgrowth in SH-SY5Y cells, with the neurites interconnected to form a network. Spontaneous discharge activity was observed in SH-SY5Y cells treated with low concentrations of adapalene. Compared to the control group, the expression of βIII-tubulin and NFH increased in the 1 μM adapalene group, while the level of cell apoptosis increased in the high concentration adapalene group (<0.05).
CONCLUSIONS
Low concentrations of adapalene can induce differentiation of SH-SY5Y cells into mature functional neurons, while high concentrations of adapalene can induce apoptosis in SH-SY5Y cells.
Topics: Humans; Tubulin; Neuroblastoma; Neurons; Cell Differentiation; Apoptosis; Cell Line, Tumor
PubMed: 38557381
DOI: 10.7499/j.issn.1008-8830.2310100 -
The Medical Journal of Malaysia Mar 2024Acne is a common skin disease with a high psychosocial burden, affecting mostly adolescents and youth worldwide. Management of acne is often challenged by cutaneous side... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Acne is a common skin disease with a high psychosocial burden, affecting mostly adolescents and youth worldwide. Management of acne is often challenged by cutaneous side effects that leads to therapeutic intolerance, poor compliance and impaired efficacy.
MATERIALS AND METHODS
This was a single-centre, evaluatorblinded, split-face, randomised study investigating the effects of thermal spring water (TSW) in improving efficacy and tolerability of standard acne therapy. Total of 31 participants with mild-to-moderate acne were recruited and subjected to TSW spray to one side of the face 4 times daily for 6 weeks in addition to standard therapy. The other side received standard therapy only.
RESULTS
Six (19.4%) males and 25 (80.6%) female with mean age 25.1±6.13 participated, 15 (48.4%) had mild acne while 16 (51.6%) had moderate acne. Seven (22.6%) were on oral antibiotics, 25 (80.6%) used adapalene, 6 (19.4%) tretinoin and 21 (67.7%) benzoyl peroxide. Skin hydration improved and better on spring water treated side with mean difference12.41±30.31, p = 0.04 at the forehead, 39.52±65.14, p < 0.01 at the cheek and 42.172±71.71, p < 0.01 at the jaw at week 6. Participants also report significant reduction in dryness at the treated side at week 6, mean difference 0.93±0.10, p < 0.001. TEWL, sebum and pH were comparable on both sides with no significant differences. Tolerability towards standard therapy improved as early week 2 with reduction of stinging following application of topical therapy (mean difference 0.62±1.43, p = 0.03), increase in skin feeling good (-1.79±1.70, p < 0.001) and skin suppleness (0.62±1.43, p < 0.001). These improvements were significantly maintained till week 6. Cardiff acne disability index significantly improved at week 6 (p<0.001) despite no significant changes in Comprehensive Acne Severity Scale score before and after treatment.
CONCLUSION
TSW may have a role as an adjunct to standard acne therapy by improving hydration, acne disability index and tolerability towards standard topical treatment.
Topics: Adolescent; Adult; Female; Humans; Male; Young Adult; Acne Vulgaris; Adapalene; Benzoyl Peroxide; Hot Springs; Prospective Studies; Treatment Outcome
PubMed: 38553920
DOI: No ID Found -
Pharmaceutics Feb 2024Acne vulgaris is a common dermatologic disorder that affects approximately 85% of teenagers, which significantly impacts the quality of life in adolescents. It is a... (Review)
Review
Acne vulgaris is a common dermatologic disorder that affects approximately 85% of teenagers, which significantly impacts the quality of life in adolescents. It is a chronic disease of the sebaceous follicles that is multifactorial in etiology. Topical treatment is the first choice for mild and moderate acne, while systemic therapy is reserved for severe and certain moderate cases. Topical treatments include retinoids (e.g., tretinoin and adapalene), antibiotics (e.g., clindamycine), and other agents (e.g., benzoyl peroxide and azelaic acid), often applied in combination. The mechanisms of action include antimicrobial, anti-inflammatory, and keratolytic activities, as well as sebum secretion reduction, and the normalization of follicular keratinization. However, these topical agents commonly induce side effects, such as dryness, burning, stinging, peeling, redness, erythema, and photosensitivity. Therefore, there is a need to reduce the side effects of anti-acne drugs, while maintaining or enhancing their therapeutic effectiveness. This article aims to comprehensively outline nanotechnology strategies, particularly the use of phospholipid-based nanocarriers like liposomes and related vesicles, to enhance therapeutic efficacy, skin tolerability, and patient compliance in the treatment of acne vulgaris. In addition, novel active ingredients encapsulated in vesicles beyond those recommended in official guidelines are discussed.
PubMed: 38543203
DOI: 10.3390/pharmaceutics16030309 -
Journal of Cutaneous Medicine and... Mar 2024
PubMed: 38468210
DOI: 10.1177/12034754241239269