scholarly journals Epigenetic histone modulation contributes to improvements in inflammatory bowel disease via EBI3

2020 ◽  
Vol 77 (23) ◽  
pp. 5017-5030 ◽  
Author(s):  
Alexandra Wetzel ◽  
Bettina Scholtka ◽  
Christian Gerecke ◽  
Burkhard Kleuser
Keyword(s):  
Histone Acetylation ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Option ◽  
Human Colon ◽  
Epigenetic Mechanism ◽  
Local Formation ◽  
Cytokine Levels ◽  
Anti Inflammatory

Abstract Ulcerative colitis (UC) is characterized by relapsing–remitting inflammatory episodes paralleled by varying cytokine levels, suggesting that switching epigenetic processes might be involved. However, the epigenetic impact on cytokine levels in colitis is mostly unexplored. The heterodimeric interleukin (IL)-12 cytokine family have various functions in both pro- and anti-inflammatory processes. The family member IL-35 (EBI3/IL-12p35) was recently reported to play an anti-inflammatory role in UC. Therefore, we aimed to investigate a possible epigenetic regulation of the IL-35 subunits in vitro and in vivo, and to examine the epigenetic targeting of EBI3 expression as a therapeutic option for UC. Exposure to either the pro-inflammatory TNFα or to histone deacetylase inhibitors (HDACi) significantly increased EBI3 expression in Human Colon Epithelial Cells (HCEC) generated from healthy tissue. When applied in combination, a drastic upregulation of EBI3 expression occurred, suggesting a synergistic mechanism. Consequently, IL-35 was increased as well. In vivo, the intestines of HDACi-treated wild-type mice exhibited reduced pathological signs of colitis compared to non-treated colitic mice. However, the improvement by HDACi treatment was completely lost in Ebi3-deficient mice (Ebi3−/−). In fact, HDACi appeared to exacerbate the disease phenotype in Ebi3−/−. In conclusion, our results reveal that under inflammatory conditions, EBI3 is upregulated by the epigenetic mechanism of histone acetylation. The in vivo data show that the deficiency of EBI3 plays a key role in colitis manifestation. Concordantly, our data suggest that conditions promoting histone acetylation, such as upon HDACi application, improve colitis by a mechanism involving the local formation of the anti-inflammatory cytokine IL-35.

scholarly journals Combining Ceftriaxone with Doxycycline and Daptomycin Reduces Mortality, Neuroinflammation, Brain Damage, and Hearing Loss in Infant Rat Pneumococcal Meningitis

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Lukas Muri ◽  
Michael Perny ◽  
Jonas Zemp ◽  
Denis Grandgirard ◽  
Stephen L. Leib
Keyword(s):  
Adjuvant Therapy ◽  
Antibiotic Therapy ◽  
Brain Damage ◽  
Pneumococcal Meningitis ◽  
Therapeutic Option ◽  
Case Fatality ◽  
Content Type ◽  
Anti Inflammatory

ABSTRACTDespite appropriate antibiotic therapy, pneumococcal meningitis (PM) is associated with a case fatality rate of up to 30% in high-income countries. Survivors often suffer from severe lifelong disabilities. An excessive inflammatory reaction drives the pathophysiology, leading to brain damage and neurologic sequelae. We aimed to improve the outcome of experimental PM by simultaneously targeting different pathophysiological mechanisms with combined adjunctive therapies previously shown to be neuroprotective.In vitro, the anti-inflammatory effects of doxycycline and daptomycin were evaluated on primary rat astroglial cells stimulated withStreptococcus pneumoniae. Eleven-day-old infant Wistar rats were infected intracisternally withS. pneumoniaeand randomized for treatment with ceftriaxone or combination adjuvant therapy consisting of ceftriaxone, daptomycin, and doxycycline. During acute PM, combined-adjuvant therapy with ceftriaxone, daptomycin, and doxycycline increased the survival rate from 64.1% to 85.8% (P < 0.01) and alleviated weight loss compared to ceftriaxone monotherapy (P < 0.01). Levels of inflammatory cytokines were significantly reduced by combined-adjuvant therapyin vitro(P < 0.0001) and in cerebrospinal fluidin vivo(P < 0.05). In infected animals treated with combined adjunctive therapy, cortical damage was significantly reduced (P < 0.05), and animals showed a trend toward better hearing capacity 3 weeks after the infection (P = 0.089), an effect which was significant in mildly infected animals (48 decibels [dB] versus 67.22 dB;P < 0.05). These mildly infected animals showed significantly reduced cochlear fibrous occlusion (P < 0.01). By combining nonbacteriolytic daptomycin and anti-inflammatory doxycycline with ceftriaxone, the previously reported beneficial effects of the drugs were cumulated and identified the triple-antibiotic therapy as a promising therapeutic option for pediatric PM.

scholarly journals Marinobufagenin Inhibits Neutrophil Migration and Proinflammatory Cytokines

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Deyse C. M. Carvalho ◽  
Luiz Henrique Agra Cavalcante-Silva ◽  
Éssia de A. Lima ◽  
José G. F. M. Galvão ◽  
Anne K. de A. Alves ◽  
...  
Keyword(s):  
Cell Migration ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Biological Activities ◽  
Neutrophil Migration ◽  
Peritoneal Macrophages ◽  
Cytokine Levels ◽  
Anti Inflammatory

Cardiotonic steroids, such as ouabain and digoxin, are known to bind to Na+/K+-ATPase and to promote several biological activities, including anti-inflammatory activity. However, there are still no reports in the literature about inflammation and marinobufagenin, a cardiotonic steroid from the bufadienolide family endogenously found in mammals. Therefore, the aim of this work was to analyze, in vivo and in vitro, the role of marinobufagenin in acute inflammation. Swiss mice were treated with 0.56 mg/kg of marinobufagenin intraperitoneally (i.p.) and zymosan (2 mg/mL, i.p.) was used to induce peritoneal inflammation. Peritoneal fluid was collected and used for counting cells by optical microscopy and proinflammatory cytokine quantification (IL-1β, IL-6, and TNF-α) by immunoenzymatic assay (ELISA). Zymosan stimulation, as expected, induced increased cell migration and proinflammatory cytokine levels in the peritoneum. Marinobufagenin treatment reduced polymorphonuclear cell migration and IL-1β and IL-6 levels in the peritoneal cavity, without interfering in TNF-α levels. In addition, the effect of marinobufagenin was evaluated using peritoneal macrophages stimulated by zymosan (0.2 mg/mL) in vitro. Marinobufagenin treatment at different concentrations (10, 100, 1000, and 10000 nM) showed no cytotoxic effect on peritoneal macrophages. Interestingly, the lowest concentration, which did not inhibit Na+/K+-ATPase activity, attenuated proinflammatory cytokines IL-1β, IL-6, and TNF-α levels. To investigate the putative mechanism of action of marinobufagenin, the expression of surface molecules (TLR2 and CD69) and P-p38 MAPK were also evaluated, but no significant effect was observed. Thus, our results suggest that marinobufagenin has an anti-inflammatory role in vivo and in vitro and reveals a novel possible endogenous function of this steroid in mammals.

scholarly journals Manipulating Histone Acetylation Leads to Adverse Effects in Hemangiosarcoma Cells

2021 ◽  
Author(s):  
Tamami Suzuki ◽  
Keisuke Aoshima ◽  
Jumpei Yamazaki ◽  
Atsushi Kobayashi ◽  
Takashi Kimura
Keyword(s):  
Histone Acetylation ◽  
Cell Lines ◽  
Histone Deacetylase Inhibitors ◽  
Epigenetic Modification ◽  
Malignant Tumour ◽  
Tumour Immunity ◽  
Cancer Pathogenesis ◽  
Induced Apoptosis

AbstractCanine hemangiosarcoma (HSA) is a malignant tumour derived from endothelial cells. No effective treatment has yet been developed because of the lack of understanding of its pathogenesis. Histone acetylation, an epigenetic modification, is highly associated with cancer pathogenesis. Manipulating histone acetylation by histone deacetylase inhibitors (HDACi) or bromodomain and extraterminal domain inhibitors (BETi) is one approach to treat various cancers. However, the role of histone acetylation in HSA remains unknown. This study aimed to investigate how histone acetylation functions in HSA pathogenesis using two HDACi, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), and one BETi, JQ1, in vitro and in vivo. Histone acetylation levels were high in cell lines and heterogeneous in clinical cases. SAHA and JQ1 induced apoptosis in HSA cell lines. SAHA and VPA treatment in HSA cell lines upregulated inflammatory-related genes, thereby attracting macrophages. This implies that SAHA and VPA can induce anti-tumour immunity. JQ1 stimulated autophagy and inhibited the cell cycle. Finally, JQ1 suppressed HSA tumour cell proliferation in vivo. These results suggest that HDACi and BETi can be alternative drugs for HSA treatment. Although further research is required, this study provides useful insights for developing new treatments for HSA.

scholarly journals Mesenchymal Stem Cell Therapy Ameliorates Metabolic Dysfunction and Restores Fertility in a PCOS Mouse Model Through Interleukin-10

2021 ◽  
Author(s):  
Rishi Man Chugh ◽  
Hang-soo Park ◽  
Abdeljabar El Andaloussi ◽  
Amro Elsharoud ◽  
Sahar Esfandyari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polycystic Ovary ◽  
Therapeutic Option ◽  
Interleukin 10 ◽  
Reproductive Age ◽  
Metabolic Dysfunction ◽  
Mesenchymal Stem Cell Therapy ◽  
Anti Inflammatory

Abstract Background: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models.Methods: For in vitro experiment, we treated conditioned media from BM-hMSC to androgen producing H293R cells, and analyzed androgen producing gene expression. For in vivo experiment, BM-hMSC were implanted into Letrozole (LTZ) induced mouse PCOS model. BM-hMSC effect in androgen producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery.Results: BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improve in metabolic and reproductive markers in our PCOS model and able to restore fertility. Conclusion: Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment.

Gigantol Alleviates IL-1β-Induced Inflammation and Catabolism in Mouse Osteoarthritis via PI3K/Akt/NF-κB Pathways In Vivo and In Vitro

2021 ◽  
Author(s):  
Gaosheng Zhu ◽  
Keze Miao ◽  
Mingwei Dong ◽  
Jie Cai ◽  
Zhihao Shen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Option ◽  
Interleukin 1 ◽  
Cartilage Degradation ◽  
Research Society ◽  
Necrosis Factor Alpha ◽  
Persistent Inflammation ◽  
Anti Inflammatory

Abstract Osteoarthritis (OA), a prevalent disabling disease, is characterized by irreversible cartilage degradation and persistent inflammation. The etiology as well as pathogenesis of OA are not completely unclear and need further investigation. Gigantol, is a bibenzyl derivative extracted from Dendrobium plants and has been found exhibit multiple effects such as anti-inflammatory effects. Nevertheless, the biological function of gigantol on osteoarthritis (OA) is still uncertain. This study aimed at examining the anti-inflammatory effects and latent mechanisms of gigantol in IL-1β-mediated OA progression. In vitro, we identified that gigantol treatment suppressed tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) in interleukin-1 beta (IL-1β) mediated mouse OA chondrocytes. Gigantol was also shown to dose dependently downregulate the metalloproteinase 13 (MMP13) as well as thrombospondin motifs 5 (ADAMTS5) levels. Moreover, IL-1β-mediated AKT and PI3K phosphorylation as well as NF-κB activation were inhibited by gigantol. Meanwhile, in vivo, we detected that gigantol treatment inhibited degradation of the cartilage degradation and lowered the Osteoarthritis Research Society International scores (OARSI) in OA mouse. Therefore, gigantol is a promising therapeutic option for OA.

scholarly journals Differential regulation of DNA methylation versus histone acetylation in cardiomyocytes during HHcy in vitro and in vivo: an epigenetic mechanism

2014 ◽  
Vol 46 (7) ◽  
pp. 245-255 ◽  
Author(s):  
Pankaj Chaturvedi ◽  
Anuradha Kalani ◽  
Srikanth Givvimani ◽  
Pradip Kumar Kamat ◽  
Anastasia Familtseva ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Acetylation ◽  
Dna Methyltransferase ◽  
Epigenetic Mechanism ◽  
Dependent Manner ◽  
Histone Deacetylase 1 ◽  
H3k9 Acetylation ◽  
Dose Dependent

The mechanisms of homocysteine-mediated cardiac threats are poorly understood. Homocysteine, being the precursor to S-adenosyl methionine (a methyl donor) through methionine, is indirectly involved in methylation phenomena for DNA, RNA, and protein. We reported previously that cardiac-specific deletion of N-methyl-d-aspartate receptor-1 (NMDAR1) ameliorates homocysteine-posed cardiac threats, and in this study, we aim to explore the role of NMDAR1 in epigenetic mechanisms of heart failure, using cardiomyocytes during hyperhomocysteinemia (HHcy). High homocysteine levels activate NMDAR1, which consequently leads to abnormal DNA methylation vs. histone acetylation through modulation of DNA methyltransferase 1 (DNMT1), HDAC1, miRNAs, and MMP9 in cardiomyocytes. HL-1 cardiomyocytes cultured in Claycomb media were treated with 100 μM homocysteine in a dose-dependent manner. NMDAR1 antagonist (MK801) was added in the absence and presence of homocysteine at 10 μM in a dose-dependent manner. The expression of DNMT1, histone deacetylase 1 (HDAC1), NMDAR1, microRNA (miR)-133a, and miR-499 was assessed by real-time PCR as well as Western blotting. Methylation and acetylation levels were determined by checking 5′-methylcytosine DNA methylation and chromatin immunoprecipitation. Hyperhomocysteinemic mouse models (CBS+/−) were used to confirm the results in vivo. In HHcy, the expression of NMDAR1, DNMT1, and matrix metalloproteinase 9 increased with increase in H3K9 acetylation, while HDAC1, miR-133a, and miR-499 decreased in cardiomyocytes. Similar results were obtained in heart tissue of CBS+/− mouse. High homocysteine levels instigate cardiovascular remodeling through NMDAR1, miR-133a, miR-499, and DNMT1. A decrease in HDAC1 and an increase in H3K9 acetylation and DNA methylation are suggestive of chromatin remodeling in HHcy.

scholarly journals Cped1 promotes chicken SSCs formation with the aid of histone acetylation and transcription factor Sox2

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Chen Zhang ◽  
Fei Wang ◽  
Qisheng Zuo ◽  
Changhua Sun ◽  
Jing Jin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Histone Acetylation ◽  
Histone Deacetylase Inhibitors ◽  
Embryonic Stem ◽  
Control Area ◽  
Luciferase Reporter ◽  
Marker Genes

Spermatogonial stem cells (SSCs) may apply to gene therapy, regenerative medicine in place of embryonic stem cells (ESCs). However, the application of SSCs was severely limited by the low induction efficiency and the lack of thorough analysis of the regulatory mechanisms of SSCs formation. Current evidences have demonstrated multiple marker genes of germ cells, while genes that specifically regulate the formation of SSCs have not been explored. In our study, cadherin-like and PC-esterase domain containing 1 (Cped1) expressed specifically in SSCs based on RNA-seq data analysis. To study the function of Cped1 in the formation of SSCs, we successfully established a CRISPR/Cas9 knockout system. The gene disruption frequency is 37% in DF1 and 25% in ESCs without off-target effects. Knockout of Cped1 could significantly inhibit the formation of SSCs in vivo and in vitro. The fragment of −1050 to −1 bp had the activity as Cped1 gene promoter. Histone acetylation could regulate the expression of Cped1. We added 5-azaeytidi (DNA methylation inhibitors) and TSA (histone deacetylase inhibitors) respectively during the cultivation of SSCs. TSA was validated to promote the transcription of Cped1. Dual-luciferase reporter assay revealed that active control area of the chicken Cped1 gene is −296 to −1 bp. There are Cebpb, Sp1, and Sox2 transcription factor binding sites in this region. Point-mutation experiment results showed that Sox2 negatively regulates the transcription of Cped1. Above results demonstrated that Cped1 is a key gene that regulates the formation of SSCs. Histone acetylation and transcription factor Sox2 participate in the regulation of Cped1.

scholarly journals Mesenchymal stem cell therapy ameliorates metabolic dysfunction and restores fertility in a PCOS mouse model through interleukin-10

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rishi Man Chugh ◽  
Hang-soo Park ◽  
Abdeljabar El Andaloussi ◽  
Amro Elsharoud ◽  
Sahar Esfandyari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Polycystic Ovary ◽  
Therapeutic Option ◽  
Interleukin 10 ◽  
Reproductive Age ◽  
Mesenchymal Stem Cell Therapy ◽  
Anti Inflammatory

Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models. Methods For in vitro experiment, we treated conditioned media from BM-hMSC to androgen-producing H293R cells and analyzed androgen-producing gene expression. For in vivo experiment, BM-hMSC were implanted into letrozole (LTZ)-induced PCOS mouse model. BM-hMSC effect in androgen-producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery. Results BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improved in metabolic and reproductive markers in our PCOS model and able to restore fertility. Conclusion Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment.

scholarly journals CKD-5, a novel pan-histone deacetylase inhibitor, synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Young Chang ◽  
Yun Bin Lee ◽  
Eun Ju Cho ◽  
Jeong-Hoon Lee ◽  
Su Jong Yu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Microarray Analysis ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Option ◽  
Hypoxic Conditions ◽  
In Vivo Experiments ◽  
Induced Apoptosis ◽  
Hcc Cells

Abstract Background Histone deacetylase inhibitors (HDACIs) have distinctive epigenetic targets involved in hepatocarcinogenesis and chemoresistance. A recent phase I/II study reported the possibility of HDACI as a chemosensitizer in sorafenib-resistant patients. In this study, we evaluated whether CKD-5, a novel pan-HDACI, can potentiate the efficacy of sorafenib. Methods The anticancer effect of CKD-5 with and without sorafenib was evaluated in vitro using an MTS assay with human HCC cells (SNU-3058 and SNU-761) under both normoxic and hypoxic conditions. Microarray analysis was performed to investigate the mechanism of cell death, which was also evaluated by small interfering RNA (siRNA) transfection and subsequent immunoblot assays. In vivo experiments were conducted using two different murine HCC models. C3H mice implanted with MH134 cells and C57BL/6 mice implanted with RIL-175 cells were treated with weekly CKD-5 with and without sorafenib for 2 weeks. Results CKD-5 treatment significantly suppressed human HCC cell growth in both normoxic and hypoxic conditions. Microarray analysis and real-time PCR showed that CKD-5 treatment significantly increased peripherin expression in HCC cells and that downregulation of peripherin by siRNA decreased CKD-5-induced apoptosis. The combination of CKD-5 and sorafenib decreased cell viability more effectively than sorafenib or CKD-5 monotherapy in human and murine HCC cells. The effectiveness of the combination therapy was consistently demonstrated in the animal models. Histological and biochemical analyses demonstrated good tolerance of CKD-5 plus sorafenib in vivo. Conclusion CKD-5 may enhance sorafenib efficacy through epigenetic regulation. The combination of CKD-5 and sorafenib might be a novel therapeutic option for the treatment of HCC.

scholarly journals Pharmacological features of osthole

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Agata Jarząb ◽  
Aneta Grabarska ◽  
Krystyna Skalicka-Woźniak ◽  
Andrzej Stepulak
Keyword(s):  
Tumor Cells ◽  
Therapeutic Option ◽  
Inhibitory Effect ◽  
Experimental Models ◽  
Naturally Occurring ◽  
Anti Cancer ◽  
Anti Inflammatory ◽  
The Impact

Coumarins are a group of naturally occurring compounds common in the plant world. These substances and their derivatives exhibit a broad range of biological activities.One of the naturally occurring coumarins is osthole, which can most frequently be found in plants of the Apiaceae family. Cnidium monnieri (L.) Cusson ex Juss. Angelica pubescens Maxim. and Peucedanum ostruthium (L.). It has anti-proliferative, anti-inflammatory, anti-convulsant, and antiallergic properties; apart from that, inhibition of platelet aggregation has also been proved. The impact of osthole on bone metabolism has been demonstrated; also its hepatoprotective and neuroprotective properties have been confirmed. The inhibitory effect of this metokcompound on the development of neurodegenerative diseases has been proved in experimental models. Anticancer features of osthole have been also demonstrated both in vitro on different cell lines, and in vivo using animals xenografts. Osthole inhibited proliferation, motility and invasiveness of tumor cells, which may be associated with the induction of apoptosis and cell cycle slowdown. The exact molecular mechanism of osthole anti-cancer mode of action has not been fully elucidated. A synergistic effect of osthole with other anti-tumor substances has been also reported. Modification of its chemical structure led to the synthesis of many derivatives with significant anticancer effects.To sum up, osthole is an interesting therapeutic option, due to both its direct effect on tumor cells, as well as its neuroprotective or anti-inflammatory properties. Thus, there is a chance to use osthole or its synthetic derivatives in the treatment of cancer.

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