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Journal of Dermatological Science Dec 2023
Topics: Ficusin; Proteomics; Skin; Ultraviolet Therapy; PUVA Therapy; Methoxsalen
PubMed: 37914600
DOI: 10.1016/j.jdermsci.2023.09.004 -
BioRxiv : the Preprint Server For... Jun 2023Cigarette smoking remains the leading preventable cause of disease and death. Nicotine is the primary reinforcing ingredient in cigarettes sustaining addiction. Cotinine...
Cigarette smoking remains the leading preventable cause of disease and death. Nicotine is the primary reinforcing ingredient in cigarettes sustaining addiction. Cotinine is the major metabolite of nicotine that produces a myriad of neurobehavioral effects. Cotinine supported self-administration and rats with a history of intravenous self-administration of cotinine exhibited relapse-like drug-seeking behavior, suggesting cotinine may also be reinforcing. To date, a potential contribution of cotinine to nicotine reinforcement remains unknown. Nicotine metabolism is mainly catalyzed by hepatic CYP2B1 enzyme in the rat and methoxsalen is a potent CYP2B1 inhibitor. The study tested the hypothesis that methoxsalen inbibits nicotine metabolism and self-administration, and that cotinine replacement attenuates the inhibitory effects of methoxsalen. Acute methoxsalen decreased plasma cotinine levels and increased nicotine levels following subcutaneous nicotine injection. Repeated methoxsalen reduced the acquisition of nicotine self-administration, leading to fewer nicotine infusions, disruption of lever differentiation, smaller total nicotine intake, and lower plasma cotinine levels. On the other hand, methoxsalen did not alter nicotine self-administration during the maintenance phase despite great reduction of plasma cotinine levels. Cotinine replacement by mixing cotinine with nicotine for self-administration dose-dependently increased plasma cotinine levels, counteracted effects of methoxsalen, and enhanced the acquisition of self-administration. Neither basal nor nicotine-induced locomotor activity was altered by methoxsalen. These results indicate that methoxsalen depressed cotinine formation from nicotine and the acquisition of nicotine self-administration, and that replacement of plasma cotinine attenuated the inhibitory effects of methoxsalen, suggesting that cotinine may contribute to the development of nicotine reinforcement.
PubMed: 37333320
DOI: 10.1101/2023.06.04.543614 -
Biomedicine & Pharmacotherapy =... Jul 2023Thrombocytopenia is a common hematological disease caused by many factors. It usually complicates critical diseases and increases morbidity and mortality. The treatment...
BACKGROUND
Thrombocytopenia is a common hematological disease caused by many factors. It usually complicates critical diseases and increases morbidity and mortality. The treatment of thrombocytopenia remains a great challenge in clinical practice, however, its treatment options are limited. In this study, the active monomer xanthotoxin (XAT) was screened out to explore its medicinal value and provide novel therapeutic strategies for the clinical treatment of thrombocytopenia.
METHODS
The effects of XAT on megakaryocyte differentiation and maturation were detected by flow cytometry, Giemsa and phalloidin staining. RNA-seq identified differentially expressed genes and enriched pathways. The signaling pathway and transcription factors were verified through WB and immunofluorescence staining. Tg (cd41: eGFP) transgenic zebrafish and mice with thrombocytopenia were used to evaluate the biological activity of XAT on platelet formation and the related hematopoietic organ index in vivo.
RESULTS
XAT promoted the differentiation and maturation of Meg-01 cells in vitro. Meanwhile, XAT could stimulate platelet formation in transgenic zebrafish and recover platelet production and function in irradiation-induced thrombocytopenia mice. Further RNA-seq prediction and WB verification revealed that XAT activates the IL-1R1 target and MEK/ERK signaling pathway, and upregulates the expression of transcription factors related to the hematopoietic lineage to promote megakaryocyte differentiation and platelet formation.
CONCLUSION
XAT accelerates megakaryocyte differentiation and maturation to promote platelet production and recovery through triggering IL-1R1 and activating the MEK/ERK signaling pathway, providing a new pharmacotherapy strategy for thrombocytopenia.
Topics: Mice; Animals; Thrombopoiesis; Blood Platelets; Megakaryocytes; Methoxsalen; Zebrafish; Thrombocytopenia; Transcription Factors; Signal Transduction; Mitogen-Activated Protein Kinase Kinases
PubMed: 37156117
DOI: 10.1016/j.biopha.2023.114811 -
Journal of Food Protection Jun 2023In this research, we evaluated the aphicidal effect of the ethanolic extract of stems and bark of Ficus petiolaris Kunth (Moraceae), in laboratory bioassays in an...
In this research, we evaluated the aphicidal effect of the ethanolic extract of stems and bark of Ficus petiolaris Kunth (Moraceae), in laboratory bioassays in an artificial diet against apterous adult females of Melanaphis sacchari Zehntner (Hemiptera: Aphididae). The extract was evaluated at different concentrations (500, 1,000, 1,500, 2,000, and 2,500 ppm), and the highest percentage of mortality (82%) was found at 2,500 ppm after 72 h. The positive control imidacloprid (Confial®) at 1% eliminated 100% of the aphids, and the negative control (artificial diet) only presented mortality of 4%. The chemical fractionation of the stem and bark extract of F. petiolaris yielded five fractions of FpR1-5, which were each evaluated at 250, 500, 750, and 1,000 ppm. FpR2 had the strongest aphicidal effect, with 89% mortality at 72 h at 1,000 ppm. The pure xanthotoxin compound extracted from this fraction was even more effective, with 91% aphid mortality after 72 h at 100 ppm. The lethal concentration (LC) of xanthotoxin was 58.7 ppm (72 h). Our results indicate that the extract of F. petiolaris showed toxic activity against this aphid, and its xanthotoxin compound showed strong aphicidal activity at low concentrations.
Topics: Animals; Female; Aphids; Ficus; Methoxsalen; Sorghum; Plant Extracts
PubMed: 37019182
DOI: 10.1016/j.jfp.2023.100084 -
Evidence-based Complementary and... 2022Keyin pill (KP), a patented medicine in China, is used to treat psoriasis. However, KP has been reported to have liver toxicity, but its toxic substance basis and...
BACKGROUND
Keyin pill (KP), a patented medicine in China, is used to treat psoriasis. However, KP has been reported to have liver toxicity, but its toxic substance basis and underlying mechanisms remain unclear. Therefore, this study aimed to explore the pharmacological mechanisms and components of KP-induced liver injury through animal experiments, UPLC-QTOF/MS combined with network pharmacology.
METHODS
Firstly, based on the immune stress mouse model, liver function parameters and hematoxylin-eosin (H&E) staining were detected to investigate KP-induced liver injury. The UPLC-QTOF/MS method was used to identify the components of KP. CTD database and literature mining were further applied to screen nonliver protective components. Subsequently, the nonliver protective components and their corresponding targets and targets of hepatotoxicity were analyzed by the method of network pharmacology. Finally, key targets from networked pharmacology were examined by the enzyme-linked immunosorbent assay (ELISA) and molecular docking.
RESULTS
Our results indicated that KP had hepatotoxicity in male Kunming mice, which could favor hepatocyte necrosis and infiltration of inflammatory cells. A total of 70 nonliver protective compounds were identified and screened. The results of network pharmacology illustrated that methoxsalen, obacunone, limonin, and dictamnine might be the main compounds that caused liver damage. The potential hepatotoxicity mechanisms of KP might be through the IL17 and apoptosis pathways to regulate IL6, TNF, CASP3, and CASP8 targets, thereby causing inflammation, excessive release of factors, and hepatocyte necrosis. The results of the ELISA experiments indicated that KP could increase the release of IL6 and TNF inflammatory factors in liver tissues. Molecular docking suggested that methoxsalen, obacunone, limonin, and dictamnine had moderate binding ability with CASP3 and CASP8.
CONCLUSION
In this study, the material basis and potential pharmacological mechanisms of KP-induced liver injury were preliminarily explored. Our research provides the initial theoretical basis for reducing the toxicity of KP.
PubMed: 36518852
DOI: 10.1155/2022/9916949 -
Molecules (Basel, Switzerland) Sep 2022essential oils are routinely adulterated because of the lack of regulations or reliable authentication methods. Unfortunately, the relatively simple chemical makeup and...
essential oils are routinely adulterated because of the lack of regulations or reliable authentication methods. Unfortunately, the relatively simple chemical makeup and the tremendous price variations among varieties encouraged the interspecies adulteration of citrus oils. In this study, a sensitive UPLC-MS/MS method for the quantitation of 14 coumarins and furanocoumarins is developed and validated. This method was applied to screen the essential oils of 12 different species. This study, to our knowledge, represents the most comprehensive investigation of coumarin and furanocoumarin profiles across commercial-scale oils to date. Results show that the lowest amount was detected in calamansi oil. Expressed oil of Italian bergamot showed the highest furanocoumarin content and the highest level of any individual furanocoumarin (bergamottin). Notable differences were observed in the coumarin and furanocoumarin levels among oils of different crop varieties and origins within the same species. Potential correlations were observed between bergapten and xanthotoxin which matches with known biosynthetic pathways. We found patterns in furanocoumarin profiles that line up with known variations among the ancestral taxa. However, contrary to the literature, we also detected xanthotoxin in sweet orange and members of the mandarin taxon. Using multivariate analysis, we were able to divide the oils into 5 main groups and correlate them to the coumarin compositions.
Topics: 5-Methoxypsoralen; Chromatography, Liquid; Citrus; Coumarins; Furocoumarins; Methoxsalen; Oils, Volatile; Plant Oils; Tandem Mass Spectrometry
PubMed: 36234812
DOI: 10.3390/molecules27196277 -
The Cochrane Database of Systematic... Sep 2022Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of... (Review)
Review
BACKGROUND
Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of paediatric recipients. Currently, the therapeutic mainstay for aGvHD is treatment with corticosteroids. However, there is no established standard treatment for steroid-refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of immunomodulatory method amongst different therapeutic options that involves ex vivo collection of peripheral mononuclear cells, exposure to the photoactive agent 8-methoxypsoralen and ultraviolet-A radiation, and reinfusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and updated in 2015.
OBJECTIVES
To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT.
SEARCH METHODS
We searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE (PubMed) and Embase (Ovid) databases from their inception to 25 January 2021. We searched the reference lists of potentially relevant studies without any language restrictions. We searched five conference proceedings and nine clinical trial registries on 9 November 2020 and 12 November 2020, respectively.
SELECTION CRITERIA
We sought to include randomised controlled trials (RCTs) comparing ECP with or without standard treatment versus standard treatment alone in children and adolescents with aGvHD after HSCT.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection. We resolved disagreement in the selection of trials by consultation with a third review author.
MAIN RESULTS
We identified no additional studies in the 2021 review update, so there are still no studies that meet the criteria for inclusion in this review.
AUTHORS' CONCLUSIONS
The efficacy of ECP in the treatment of aGvHD in children and adolescents after HSCT is unknown, and its use should be restricted to within the context of RCTs. Such studies should address a comparison of ECP alone or in combination with standard treatment versus standard treatment alone. The 2021 review update brought about no additions to these conclusions.
Topics: Adolescent; Adrenal Cortex Hormones; Child; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Methoxsalen; Photopheresis; Steroids
PubMed: 36166494
DOI: 10.1002/14651858.CD009759.pub4 -
Scientific Reports Aug 2022Psoralen derivatives are well known for their unique phototoxicity and also exhibits promising anti-breast cancer activity both in the presence and the absence of UVA...
Psoralen derivatives are well known for their unique phototoxicity and also exhibits promising anti-breast cancer activity both in the presence and the absence of UVA irradiation. However, the structure-activity relationship on this scaffold remains lacking. Herein, a series of psoralen derivatives with various C-5 substituents were synthesized and evaluated for their in vitro dark and light-activated cytotoxicity against three breast cancer cell lines: MDA-MB-231, T47-D, and SK-BR-3. The type of substituents dramatically impacted the activity, with the 4-bromobenzyl amide derivative (3c) exhibiting the highest dark cytotoxicity against T47-D (IC = 10.14 µM), with the activity comparable to those of the reference drugs (doxorubicin, 1.46 µM; tamoxifen citrate, 20.86 µM; lapatinib 9.78 µM). On the other hand, the furanylamide 3g exhibits the highest phototoxicity against SK-BR-3 cells with the IC of 2.71 µM, which is almost tenfold increase compared to the parent compound, methoxsalen. Moreover, these derivatives showed exceptional selectivity towards HER2+ (SK-BR-3) over the HER2- (MDA-MB-231) breast cancer cell lines, which correlates well with the results from the molecular docking study, revealing that 3g formed favorable interactions within the active site of the HER2. Additionally, the cell morphology of SK-BR-3 cells suggested that the significant phototoxicity was related to induction of cell apoptosis. Most of the synthesized psoralen derivatives possess acceptable physicochemical properties and are suitable for being further developed as a novel anti-breast cancer agent in the future.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Ficusin; Humans; Molecular Docking Simulation
PubMed: 35931753
DOI: 10.1038/s41598-022-17625-x -
Experimental Dermatology Nov 2022Mycosis fungoides (MF) is a subtype of cutaneous T-cell lymphoma (CTCL). Topical or systemic treatment with psoralen, such as 8-methoxypsoralen (8-MOP), followed by...
Mycosis fungoides (MF) is a subtype of cutaneous T-cell lymphoma (CTCL). Topical or systemic treatment with psoralen, such as 8-methoxypsoralen (8-MOP), followed by ultraviolet A (UVA) irradiation (PUVA therapy) is an effective phototherapy for early-stage MF. However, the efficacy of PUVA therapy for advanced-stage MF is not satisfactory, and the ideal combination partner for PUVA therapy has not yet been found. In this study, we developed a new mouse model of CTCL in which efficacy of PUVA was detected and further evaluated the efficacy of combination treatment of PUVA and mogamulizumab, an anti-CCR4 monoclonal antibody. Cytotoxicity of PUVA therapy against HH cells, a CTCL cell line, was observed in vitro. The cytotoxicity was dependent on both 8-MOP and UVA. Using HH cells, we developed a mouse model in which HH cells were subcutaneously inoculated in the ear. In this model, PUVA therapy suppressed tumour growth with statistical significance, while 8-MOP or UVA alone did not. Combination therapy of PUVA and mogamulizumab showed greater antitumor activity than either monotherapy with statistical significance. In the histological analysis of the tumour tissue, PUVA accelerated tumour necrosis and then induced the infiltration inflammatory cells in the necrotic area, suggesting that these cells served as effector cells for mogamulizumab. This combination therapy is expected to be a beneficial option for CTCL therapy.
Topics: Animals; Mice; Ficusin; Methoxsalen; Skin Neoplasms; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; PUVA Therapy; Ultraviolet Therapy
PubMed: 35801380
DOI: 10.1111/exd.14641 -
The Cochrane Database of Systematic... Jun 2022Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation, occurring in 6% to 65% of the... (Review)
Review
Extracorporeal photopheresis versus alternative treatment for chronic graft-versus-host disease after haematopoietic stem cell transplantation in children and adolescents.
BACKGROUND
Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation, occurring in 6% to 65% of the paediatric recipients. Currently, the therapeutic mainstay for cGvHD is treatment with corticosteroids, frequently combined with other immunosuppressive agents in people with steroid-refractory manifestations. There is no established standard treatment for steroid-refractory cGvHD. The therapeutic options for these patients include extracorporeal photopheresis (ECP), an immunomodulatory treatment that involves ex vivo collection of mononuclear cells from peripheral blood, exposure to the photoactive agent 8-methoxypsoralen, ultraviolet radiation and re-infusion of the processed cell product. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and first updated in 2015.
OBJECTIVES
To evaluate the effectiveness and safety of ECP for the management of cGvHD in children and adolescents after haematopoietic stem cell transplantation.
SEARCH METHODS
We searched the Cochrane Register of Controlled Trials (CENTRAL) (2021), MEDLINE (PubMed) and Embase databases from their inception to 25 January 2021. We searched the reference lists of potentially relevant studies without any language restrictions. We searched five conference proceedings and nine clinical trial registries on 9 November 2020 and 12 November 2020, respectively.
SELECTION CRITERIA
We aimed to include randomised controlled trials (RCTs) comparing ECP with or without alternative treatment versus alternative treatment alone in children and adolescents with cGvHD after haematopoietic stem cell transplantation.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection. We resolved disagreements in the selection of trials by consultation with a third review author.
MAIN RESULTS
We found no studies meeting the criteria for inclusion in this 2021 review update.
AUTHORS' CONCLUSIONS
We could not evaluate the efficacy of ECP in the treatment of cGvHD in children and adolescents after haematopoietic stem cell transplantation since the second review update again found no RCTs. Current recommendations are based on retrospective or observational studies only. Thus, ideally, ECP should be applied in the context of controlled trials only. However, performing RCTs in this population will be challenging due to the limited number of eligible participants, variable disease presentation and the lack of well-defined response criteria. International collaboration, multicentre trials and appropriate funding for such trials will be needed. If treatment decisions based on clinical data are made in favour of ECP, recipients should be carefully monitored for beneficial and harmful effects. In addition, efforts should be made to share this information with other clinicians, for example by setting up registries for children and adolescents treated with ECP.
Topics: Adolescent; Child; Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Methoxsalen; Photopheresis; Steroids
PubMed: 35679154
DOI: 10.1002/14651858.CD009898.pub4