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Antonie Van Leeuwenhoek Feb 2020Halophytic plants growing in harsh desert environments are rich reservoirs of unique endophytic microorganisms. Here, healthy fresh plants of the families Tamaricaceae...
Halophytic plants growing in harsh desert environments are rich reservoirs of unique endophytic microorganisms. Here, healthy fresh plants of the families Tamaricaceae and Amarantaceae at three saline locations in Iran were investigated for their bioactive endophytic fungi. Among a vast number of isolates, eight isolates were identified as Humicola fuscoatra (Sordariomycetes, Pezizomycotina, Ascomycota) by microscopy and representative DNA sequences of the 5.8S rDNA (ITS) and partial β-tubulin (TUB2). Those isolates were halotolerant, and highly bioactive, so that their intra- and extra-cellular metabolites possessed in vitro antifungal, antibacterial and antiproliferative activities, against a number of fungal and bacterial plant pathogens including the fungi Arthrobotrys conoides, Pyrenophora graminea, Pyricularia grisea and the bacteria Agrobacterium tumefaciens, Pseudomonas syringae and Xanthomonas oryzae. Chemical analyses of metabolites from the endophytes using HNMR, CNMR, NOESY, COSY, HMBC, HSQC, DEPT, TOCSY and EI MASS techniques identified 3,8-dihydroxy-1-methyl-9,10-anthracenedione (aloesaponarin II; an anthraquinone derivative), 1,8,9-anthracenetriol structure (chrysarobin; an anthranol derivative) and 2,4-di-tert-butylthiophenol in fungal extracts. To the best of our knowledge, this is the first report of endophytic association of halotolerant H. fuscoatra isolates with Tamaricaceae and Amarantaceae, and their bioactivity against plant pathogens. Also, the capability of chrysarobin and aloesaponarin II production is new to the fungal kingdom. These findings may find application in agriculture, pharmacology, and biotechnology.
Topics: Amaranthaceae; Anthracenes; Anthralin; Anthraquinones; Ascomycota; DNA, Bacterial; DNA, Ribosomal; Salt-Tolerant Plants; Tamaricaceae
PubMed: 31584108
DOI: 10.1007/s10482-019-01336-x -
Journal of Dermatological Science Sep 2017Psoriasis is an inflammatory skin disease with aberrant keratinocyte proliferation, presumably as a result of immune cell activation. Th17 cytokines like IL-17A and...
BACKGROUND
Psoriasis is an inflammatory skin disease with aberrant keratinocyte proliferation, presumably as a result of immune cell activation. Th17 cytokines like IL-17A and IL-22 are critically implicated in epidermal thickening, altered keratinocyte differentiation and production of innate factors such as antimicrobial peptides. Psoriasis treatment options include modern targeted therapies using anti-cytokine antibodies and traditional non-targeted treatments like anthralin (dithranol). While the mode of action of anti-cytokine antibodies is defined, the effects of topical anthralin on psoriatic skin are not fully understood.
OBJECTIVE
This study aims to unravel the direct effects of anthralin on keratinocyte proliferation, differentiation and production of psoriasis-associated factors.
METHODS
We tested the effects of anthralin on cell proliferation, cytokeratin expression and changes in the expression of antimicrobial peptides using primary keratinocytes and 3D psoriasis tissue models with and without stimulation of the psoriasis-promoting cytokines IL-17A and IL-22. Moreover, we compared the findings derived from monolayer and multilayer cultures to data derived from lesional skin of patients with psoriasis before and under treatment with anthralin.
RESULTS
Our study shows that anthralin directly induces cell apoptosis in vitro in monolayer cultures but not in 3D psoriasis tissue models treated with IL-17A and IL-22. Yet, keratinocyte proliferation as determined by Ki-67 staining is impaired by anthralin in vivo. In lesional skin but not in 3D psoriasis tissue models anthralin rapidly normalizes cytokeratin (CK)16 expression. Furthermore, anthralin directly inhibits DEFB4 expression in vitro and in vivo, while other antimicrobial peptides and cytokines studied like IL-6 and IL-8 are regulated differently in vitro and in vivo.
CONCLUSIONS
Our results show that anthralin directly regulates DEFB4A expression. However, its beneficial effects on psoriasis cannot be explained by direct effects on keratinocyte differentiation or cytokine expression.
Topics: Administration, Cutaneous; Anthralin; Apoptosis; Biopsy; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dermatologic Agents; Fluorescent Antibody Technique; Humans; Interleukin-17; Interleukin-6; Interleukin-8; Interleukins; Keratin-10; Keratin-16; Keratin-5; Keratinocytes; Ki-67 Antigen; Psoriasis; Skin; Tissue Culture Techniques; beta-Defensins; Interleukin-22
PubMed: 28673488
DOI: 10.1016/j.jdermsci.2017.06.007 -
International Immunopharmacology Oct 2021Alopecia areata (AA) is a chronic autoimmune disorder. Finding the best treatment regimen for it remains a challenge. Currently, one of the best documented treatment... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Alopecia areata (AA) is a chronic autoimmune disorder. Finding the best treatment regimen for it remains a challenge. Currently, one of the best documented treatment modalities for AA is topical immunotherapy.
AIM
To evaluate the safety and efficacy of combined DPCP and anthralin versus standard protocol (DPCP alone).
METHODS
A prospective randomized clinical trial was conducted on 50 patients with Alopecia areata who received DPCP alone (group D) or in combination with anthralin (group D/A). Percentage of hair regrowth after 6 months of treatment and the incidence of drug-related adverse effects were evaluated and compared between the two groups.
RESULTS
Complete hair regrowth was observed among three patients in each group (18.75% in Group D and 15.79% in Group D/A) after 6 months. Moreover, 25% and 31% of patients in group D and 21% and 47% of patients in group D/A had > 75% and > 50% hair regrowth respectively at the end of the study (P-value: 0.696). In addition, earlier age of onset, chronicity of lesions, nail involvement, facial hair loss and extensive lesions at baseline were associated with poor clinical outcome.
CONCLUSION
DPCP and anthralin was as effective as DPCP alone and anthralin did not add to the effect of DPCP in treating AA.
Topics: Adolescent; Adult; Age of Onset; Alopecia Areata; Anthralin; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Female; Hair; Humans; Immunotherapy; Male; Middle Aged; Nail Diseases; Prospective Studies; Treatment Outcome; Young Adult
PubMed: 34298402
DOI: 10.1016/j.intimp.2021.107971 -
Archives of Dermatological Research Oct 2019Contact immunotherapy with diphenylcyclopropenone (DPCP) and anthralin is considered the treatment option for extensive alopecia areata (AA) unresponsive to DPCP...
Contact immunotherapy with diphenylcyclopropenone (DPCP) and anthralin is considered the treatment option for extensive alopecia areata (AA) unresponsive to DPCP immunotherapy alone. Only one study has described the efficacy of combination therapy; therefore, we investigated whether topical DPCP and anthralin can promote hair regrowth in DPCP-non responders. In this retrospective case-series we analyzed the efficacy and side effects of DPCP with anthralin in AA patients who did not respond to several months of treatment with DPCP alone. Thirty-two DPCP-nonresponsive AA patients were treated with DPCP and anthralin for the average of 8.3 ± 3.8 (3-17) months. During the treatment, 40.62% of patients (13 patients out of 32) had terminal hair regrowth. The mean of hair regrowth rate was 41%; it was mainly as partial hair regrowth (˂ 50%) and 27.27% of cases achieved > 50% terminal hair regrowth. Treatment response strongly related to the duration of combination therapy (p value ˂ 0.001), but we did not find any relation with other demographic characteristics. The first signs of response to treatment were noticed 2-12 months (5.5 ± 3.4) after initiation of combination therapy while there was a positive correlation among the duration of treatment and percentage of hair regrowth (p < 0.001). The most common complication was bullae (25%), and the least frequent side effect was generalized pruritus (3.1%). The combination therapy with DPCP and anthralin could be effective to treat DPCP non-responder AA patients. Additionally, the higher treatment response could be achieved by longer treatment duration.
Topics: Administration, Topical; Adolescent; Adult; Alopecia Areata; Anthralin; Child; Cyclopropanes; Dermatologic Agents; Drug Therapy, Combination; Female; Hair; Humans; Immunologic Factors; Male; Middle Aged; Pruritus; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult
PubMed: 31165933
DOI: 10.1007/s00403-019-01940-x -
JAMA Dermatology Jan 2020Treatment of psoriasis is associated with improved quality of life (QOL) in those with the disease. However, in daily clinical practice, the association between the...
IMPORTANCE
Treatment of psoriasis is associated with improved quality of life (QOL) in those with the disease. However, in daily clinical practice, the association between the degree of psoriasis clearance and QOL has not been studied to date, especially in the pediatric population.
OBJECTIVES
To identify the association between the degree of psoriasis improvement (as measured by the Psoriasis Area Severity Index [PASI] and body surface area [BSA] response) and QOL (as measured by the Children's Dermatology Life Quality Index [CDLQI]) in pediatric psoriasis, and to assess the association of treatment type with QOL, independent of psoriasis improvement.
DESIGN, SETTING, AND PARTICIPANTS
Data used in this single-center cohort study were extracted from the Child-CAPTURE (Continuous Assessment of Psoriasis Treatment Use Registry), a prospective, observational, daily clinical practice cohort of all children (aged <18 years) with a psoriasis diagnosis who attended the outpatient clinic of the Department of Dermatology at the Radboud University Medical Center in Nijmegen, the Netherlands, between September 3, 2008, and May 4, 2018. All records of treatment episodes with CDLQI, PASI, and BSA scores were included in the analysis.
EXPOSURES
Patients were treated according to daily clinical care. Treatments were clustered into topical, dithranol, conventional systemic, and biological treatments. Because of low numbers of UV-B phototherapy, this treatment was not assessed.
MAIN OUTCOMES AND MEASURES
Primary outcomes were mean change of CDLQI scores per PASI and BSA response categories (0 to <50, 50 to <75, 75 to <90, and ≥90) and mean CDLQI change per treatment categories.
RESULTS
In total, 319 patients (median [interquartile range] age, 10.0 [7.0] years; 183 female [57.4%]) were analyzed for PASI score improvement (399 treatment episodes) and improvement in BSA involvement (366 treatment episodes). The greatest improvements in CDLQI scores were seen in the PASI ≥90 response category, with an estimated marginal mean change in CDLQI score of -6.6 (95% CI, -7.5 to -5.7). The greatest improvements in CDLQI scores were also observed in the BSA ≥90 response category, with an estimated marginal mean change in CDLQI score of -6.8 (95% CI, -7.5 to -6.1). Systemic treatment demonstrated a greater degree of improvement of CDLQI compared with topical treatment, independent of PASI response categories.
CONCLUSIONS AND RELEVANCE
This cohort study in a real-world setting found that the greatest improvements in QOL were associated with PASI 90 or greater, a decrease in BSA involvement of 90% or greater, and systemic treatments. These findings suggest that reaching PASI 90 or greater and decreasing BSA involvement by at least 90% may be clinically meaningful treatment goals that will help pediatric patients with psoriasis reach optimal QOL.
Topics: Administration, Oral; Administration, Topical; Adolescent; Biological Products; Child; Child, Preschool; Dermatologic Agents; Female; Follow-Up Studies; Humans; Injections; Male; Netherlands; Prospective Studies; Psoriasis; Quality of Life; Severity of Illness Index; Treatment Outcome; Ultraviolet Therapy
PubMed: 31774449
DOI: 10.1001/jamadermatol.2019.3717 -
Journal of the American Academy of... Apr 2015Some patients with chronic extensive alopecia areata (AA) may be refractory to topical immunotherapy. Combination therapy is recommended for such patients. Efficacy and... (Comparative Study)
Comparative Study
BACKGROUND
Some patients with chronic extensive alopecia areata (AA) may be refractory to topical immunotherapy. Combination therapy is recommended for such patients. Efficacy and safety of a combination therapy with diphenylcyclopropenone (DPCP) and anthralin in chronic extensive AA is unknown.
OBJECTIVE
We sought to determine whether the combination therapy of DPCP and anthralin is superior to DPCP alone in chronic extensive AA.
METHODS
We retrospectively analyzed the efficacy, side effects, and relapse rates of DPCP (alone or with anthralin) in chronic extensive AA.
RESULTS
A total of 47 patients (22 were treated only with DPCP, and 25 with DPCP and anthralin for at least 30 weeks) were evaluated. Complete hair regrowth was observed in 36.4% and 72% of the patients who received DPCP and combination therapy, respectively (P = .01). Hair regrowth duration was shorter with combination therapy (P = .01). Regrowth rates of the eyebrows, eyelashes, and beard in patients on combination therapy were higher than those in patients on DPCP (P = .01). Side effects such as folliculitis, hyperpigmentation, and staining of skin, hair, and clothes were more common in combination therapy group.
LIMITATIONS
The retrospective design and small number of patients are limitations.
CONCLUSION
Combination therapy with DPCP and anthralin is superior to DPCP alone in chronic extensive AA.
Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Alopecia Areata; Anthralin; Apoptosis; CD4-CD8 Ratio; Child; Cyclopropanes; Cytokines; Drug Eruptions; Drug Evaluation; Drug Therapy, Combination; Female; Folliculitis; Follow-Up Studies; Humans; Hyperpigmentation; Immunotherapy; Male; Middle Aged; Pruritus; Retrospective Studies; Severity of Illness Index; T-Lymphocyte Subsets; Treatment Outcome; Young Adult
PubMed: 25653027
DOI: 10.1016/j.jaad.2015.01.008 -
Journal of the American Academy of... Mar 2018
Review
Topics: 11-beta-Hydroxysteroid Dehydrogenases; Alopecia Areata; Anthralin; Bimatoprost; Cyclopropanes; Dermatologic Agents; Drug Therapy, Combination; Eyebrows; Eyelashes; Facial Dermatoses; Humans; Latanoprost; Minoxidil; Photosensitizing Agents; Prostaglandins F, Synthetic
PubMed: 28987491
DOI: 10.1016/j.jaad.2017.09.054 -
The Journal of Biological Chemistry Oct 2020A sterilizing or functional cure for HIV is currently precluded by resting CD4 T cells that harbor latent but replication-competent provirus. The "shock-and-kill"...
A sterilizing or functional cure for HIV is currently precluded by resting CD4 T cells that harbor latent but replication-competent provirus. The "shock-and-kill" pharmacological ap-proach aims to reactivate provirus expression in the presence of antiretroviral therapy and target virus-expressing cells for elimination. However, no latency reversal agent (LRA) to date effectively clears viral reservoirs in humans, suggesting a need for new LRAs and LRA combinations. Here, we screened 216 compounds from the pan-African Natural Product Library and identified knipholone anthrone (KA) and its basic building block anthralin (dithranol) as novel LRAs that reverse viral latency at low micromolar concentrations in multiple cell lines. Neither agent's activity depends on protein kinase C; nor do they inhibit class I/II histone deacetylases. However, they are differentially modulated by oxidative stress and metal ions and induce distinct patterns of global gene expression from established LRAs. When applied in combination, both KA and anthralin synergize with LRAs representing multiple functional classes. Finally, KA induces both HIV RNA and protein in primary cells from HIV-infected donors. Taken together, we describe two novel LRAs that enhance the activities of multiple "shock-and-kill" agents, which in turn may inform ongoing LRA combination therapy efforts.
Topics: Anthracenes; Anthralin; Drug Evaluation, Preclinical; HIV Infections; HIV-1; Humans; Jurkat Cells; Virus Latency
PubMed: 32788215
DOI: 10.1074/jbc.RA120.013031 -
NPJ Vaccines Sep 2022Transcutaneous immunization (TCI) utilizing the TLR7 agonist imiquimod (IMQ-TCI) induces T cell-driven protective immunity upon application onto intact skin. In our...
Transcutaneous immunization (TCI) utilizing the TLR7 agonist imiquimod (IMQ-TCI) induces T cell-driven protective immunity upon application onto intact skin. In our present work, we combine the anti-psoriatic agent dithranol with IMQ-TCI to boost vaccination efficacy (Dithranol/IMQ-based transcutaneous vaccination (DIVA)). Using ovalbumin-derived peptides as model antigens in mice, DIVA induced superior cytolytic CD8 T cells and CD4 T cells with a T cytokine profile in the priming as well as in the memory phase. Regarding the underlying mechanisms, dithranol induced an oxidant-dependent, monocyte-attracting inflammatory milieu in the skin boosting TLR7-dependent activation of dendritic cells and macrophages leading to superior T cell priming and protective immunity in vaccinia virus infection. In conclusion, we introduce the non-invasive vaccination method DIVA to induce strong primary and memory T cell responses upon a single local treatment. This work provides relevant insights in cutaneous vaccination approaches, paving the way for clinical development in humans.
PubMed: 36153349
DOI: 10.1038/s41541-022-00530-9 -
The Journal of Organic Chemistry Jan 2020The role of the chemical environment in promoting anthralin/O reactions was discovered using neat solvents to model the amino acids of a cofactor-independent oxygenase....
The role of the chemical environment in promoting anthralin/O reactions was discovered using neat solvents to model the amino acids of a cofactor-independent oxygenase. Experimental and computational results highlight the importance of the substrate-enolate, which is accessed via energetically small, escalating steps in which the ground-state keto-isomer is tautomerized to an enol and then ionized by solvent. The resulting ion-pair is poised for spontaneous electron transfer to O. Similar activation may be exploited in biological/nonbiological oxidations involving O.
PubMed: 31830417
DOI: 10.1021/acs.joc.9b03133