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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 -
Cureus Nov 2023Skin of color refers to individuals whose skin color ranges from very light beige to very dark brown. Anthropologists and sociologists have previously recognized the...
Colorimetric Scale for Skin of Color: A Practical Classification Scale for the Clinical Assessment, Dermatology Management, and Forensic Evaluation of Individuals With Skin of Color.
Skin of color refers to individuals whose skin color ranges from very light beige to very dark brown. Anthropologists and sociologists have previously recognized the importance of an objective classification of skin color for individuals with skin of color that does not include race and ethnicity. Since 1975, dermatologists have used the Fitzpatrick classification of sun-reactive skin types to categorize patients with skin of color; this classification was established for psoriasis patients participating in using oral methoxsalen and phototherapy clinical trial to determine the initial ultraviolet A dose. The Fitzpatrick classification merely classifies individuals as white, brown, and black; the individuals with white skin are further divided into four groups based on their burning or tanning capacity. This classification system does not provide reliable information with regard to the risk of skin cancer for individuals with darker skin color and does not aid in the evaluation of medical conditions with cutaneous involvement or assessment of appropriate cosmetic interventions for aesthetic management. Many clinicians, including forensic pathologists, incorporate the patient's race or ethnicity in their medical evaluation to describe the individual's skin color. Established scales for skin of color either include white skin color, or include 10 or more color types, or include both. We introduce a simple and rapidly performed scale that is not based on race or ethnicity to categorize persons with skin of color. The colorimetric scale ranges from very light beige to very dark brown and does not include white skin. The scale has five colors ranging from lightest (skin color type 1) to darkest (skin color type 5): very light beige (skin color type 1), light brown (skin color type 2), medium brown (skin color type 3), dark brown (skin color type 4), and very dark brown (skin color type 5); an individual with white skin would have a skin color type 0 in this classification of patient skin color. In conclusion, a scale that is not based on race or ethnicity is useful for categorizing individuals with skin of color not only for sociologists but also for clinicians who treat these patients. This colorimetric scale will be helpful for dermatologists to categorize persons with skin of color to predict their risk for developing skin cancer and to assessing appropriate cosmetic procedures and devices for these patients. In addition, the colorimetric scale will be useful for not only forensic pathologists but also other clinicians to provide a non-racial and non-ethnic designation of skin color type for their patients.
PubMed: 38046737
DOI: 10.7759/cureus.48132 -
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 -
Dermatologic Clinics Oct 2015Extracorporeal photopheresis (ECP) is an immunomodulating procedure that leads to an expansion of peripheral blood dendritic cell populations and an enhanced TH1 immune... (Review)
Review
Extracorporeal photopheresis (ECP) is an immunomodulating procedure that leads to an expansion of peripheral blood dendritic cell populations and an enhanced TH1 immune response in cutaneous T-cell lymphoma (CTCL). Because of its excellent side effect profile and moderate efficacy, ECP is considered first-line therapy for erythrodermic mycosis fungoides (MF) and Sézary syndrome. Patients with a measurable but low blood tumor burden are most likely to respond to ECP, and the addition of adjunctive immunostimulatory agents may also increase response rates. There may be a role for ECP in the treatment of refractory early stage MF, but data are limited.
Topics: Antineoplastic Agents; Chemotherapy, Adjuvant; Humans; Immunomodulation; Methoxsalen; Mycosis Fungoides; Photopheresis; Photosensitizing Agents; Sezary Syndrome; Skin Neoplasms; Treatment Outcome
PubMed: 26433848
DOI: 10.1016/j.det.2015.05.011 -
Cancer Medicine Nov 2022This trial explores SM-88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) METHODS: Forty-nine... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This trial explores SM-88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) METHODS: Forty-nine patients were randomized to daily 460 or 920 mg oral SM-88 with MPS (SM-88 Regimen). The primary endpoint was objective response rate (RECIST 1.1).
RESULTS
Thirty-seven patients completed ≥ one cycle of SM-88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality-of-life (QOL) was maintained and trended in favor of 920 mg. SM-88 Regimen was well tolerated; a single patient (1/49) had related grade 3 and 4 adverse events, which later resolved. In the intention-to-treat population of 49 patients, the median overall survival (mOS) was 3.4 months (95% CI: 2.7-4.9 months). Those treated in the second line had an mOS of 8.1 months and a median PFS of 3.8 months. Survival was higher for patients with stable versus progressive disease (any line; mOS: 10.6 months vs. 3.9 months; p = 0.01).
CONCLUSIONS
SM-88 Regimen has a favorable safety profile with encouraging QOL effects, disease control, and survival trends. This regimen should be explored in the second-line treatment of patients with mPDAC.
CLINICALTRIALS
gov Identifier: NCT03512756.
Topics: Humans; Methoxsalen; Phenytoin; Antineoplastic Combined Chemotherapy Protocols; Sirolimus; Quality of Life; Pancreatic Neoplasms; Adenocarcinoma
PubMed: 35499204
DOI: 10.1002/cam4.4768 -
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 -
International Journal of Molecular... Nov 2021Cytochrome P450 2A13 is an omitted brother of CYP2A6 that has an important role in the drug metabolism of liver. Due to extrahepatic expression, it has gained less... (Review)
Review
Cytochrome P450 2A13 is an omitted brother of CYP2A6 that has an important role in the drug metabolism of liver. Due to extrahepatic expression, it has gained less attention than CYP2A6, despite the fact that it plays a significant role in toxicant-induced pulmonary lesions and, therefore, lung cancer. The purpose of this mini-review is to summarize the basic knowledge about this enzyme in relation to the substrates, inhibitors, genetic polymorphisms, and transcriptional regulation that are known so far (September 2021).
Topics: Animals; Aryl Hydrocarbon Hydroxylases; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Lung; Lung Neoplasms; Methoxsalen; Polymorphism, Genetic; Substrate Specificity
PubMed: 34830188
DOI: 10.3390/ijms222212306 -
Pharmacognosy Magazine Jul 2017Coumarins exert many biological effects in humans, animals, and plants, which make the evaluation of their biological activities and study of their role in ethnomedicine...
INTRODUCTION
Coumarins exert many biological effects in humans, animals, and plants, which make the evaluation of their biological activities and study of their role in ethnomedicine highly valued.
OBJECTIVES
Here, we selected seven plants which have ethnopharmacological use as antimicrobial in Iraq and the aims were to quantify the two structural isomers bergapten and methoxsalen in their seeds, to evaluate the antibacterial activities against several clinical isolates, and to isolate bergapten and methoxsalen from .
MATERIALS AND METHODS
Seven plants were extracted by petroleum ether (PE) and ethanol (EtOH). Bergapten and methoxsalen were separated and purified by preparative thin-layer chromatography. Quantification of the furanocoumarins has been conducted by high-performance liquid chromatography, and all the plant extracts and pure compounds were checked for antibacterial activities utilizing alamar blue microplate assay.
RESULTS
was deprived of bergapten and methoxsalen and methoxsalen was not detected from . Bergapten was abundant in PE more than in EtOH; on the other hand, EtOH was rich in methoxsalen. The separation of the two structural isomers was performed using normal phase chromatography and ultraviolet light as an indicator. All extracts showed weak to moderate antibacterial activities against Gram-positive isolates which were more sensitive than the negative ones. extract was least active, uncover the antibacterial role of bergapten and methoxsalen.
CONCLUSION
These findings support the medicinal use of seeds of seven plants from family and quantify the two pharmacologically important furanocoumarins (bergapten and methoxsalen).
SUMMARY
This study was conducted to evaluate the antibacterial activities of seven plants seeds used in local medicine in Iraq. High-performance liquid chromatography was used to quantify bergapten and xanthotoxin in non-polar and polar extracts of these seeds. This study supports the medicinal use of these plants and clarifies the role of bergapten and xanthotoxin in antibacterial activities of these plants. EtOH: Ethanol; MIC: Minimum inhibitory concentration; PE: Petroleum ether; Rf: Retardation factor; Rt: Retention time.
PubMed: 28808379
DOI: 10.4103/pm.pm_503_16 -
Current Biology : CB Jun 2018Defensive variability of crops and natural systems can alter herbivore communities and reduce herbivory [1, 2]. However, it is still unknown how defense variability...
Defensive variability of crops and natural systems can alter herbivore communities and reduce herbivory [1, 2]. However, it is still unknown how defense variability translates into herbivore suppression. Nonlinear averaging and constraints in physiological tracking (also more generally called time-dependent effects) are the two mechanisms by which defense variability might impact herbivores [3, 4]. We conducted a set of experiments manipulating the mean and variability of a plant defense, showing that defense variability does suppress herbivore performance and that it does so through physiological tracking effects that cannot be explained by nonlinear averaging. While nonlinear averaging predicted higher or the same herbivore performance on a variable defense than on an invariable defense, we show that variability actually decreased herbivore performance and population growth rate. Defense variability reduces herbivore performance in a way that is more than the average of its parts. This is consistent with constraints in physiological matching of detoxification systems for herbivores experiencing variable toxin levels in their diet and represents a more generalizable way of understanding the impacts of variability on herbivory [5]. Increasing defense variability in croplands at a scale encountered by individual herbivores can suppress herbivory, even if that is not anticipated by nonlinear averaging.
Topics: Animals; Food Chain; Herbivory; Methoxsalen; Moths; Plants
PubMed: 29887306
DOI: 10.1016/j.cub.2018.04.070 -
Bioorganic Chemistry Aug 2019Seventy-one 7-oxycoumarins, 66 synthesized and 5 commercially sourced, were tested for their ability to inhibit growth in murine PAM212 keratinocytes. Forty-nine...
Seventy-one 7-oxycoumarins, 66 synthesized and 5 commercially sourced, were tested for their ability to inhibit growth in murine PAM212 keratinocytes. Forty-nine compounds from the library demonstrated light-induced lethality. None was toxic in the absence of UVA light. Structure-activity correlations indicate that the ability of the compounds to inhibit cell growth was dependent not only on their physiochemical characteristics, but also on their ability to absorb UVA light. Relative lipophilicity was an important factor as was electron density in the pyrone ring. Coumarins with electron withdrawing moieties - cyano and fluoro at C - were considerably less active while those with bromines or iodine at that location displayed enhanced activity. Coumarins that were found to inhibit keratinocyte growth were also tested for photo-induced DNA plasmid nicking. A concentration-dependent alteration in migration on neutral gels caused by nicking was observed.
Topics: Animals; Cell Proliferation; Cells, Cultured; Coumarins; Dose-Response Relationship, Drug; Keratinocytes; Mice; Molecular Structure; Photochemical Processes; Photosensitizing Agents; Structure-Activity Relationship
PubMed: 31170642
DOI: 10.1016/j.bioorg.2019.103014