PMID: 

J Am Chem Soc. 2004 Jul 7 ;126(26):8102-3. PMID: 15225036

Abstract Title: 

Radio frequency magnetic field effects on a radical recombination reaction: a diagnostic test for the radical pair mechanism.

Abstract: 

The photoinduced electron-transfer reaction of chrysene with isomers of dicyanobenzene is used to demonstrate the sensitivity of a radical recombination reaction to the orientation and frequency (5-50 MHz) of a approximately 300 muT radio frequency magnetic field in the presence of a 0-4 mT static magnetic field. The recombination yield is detected via the fluorescence of the exciplex formed exclusively from the electronic singlet state of the radical ion pair Chr*+/DCB*-. Magnetic field effects are simulated using a modified version of the gamma-COMPUTE algorithm, devised for the simulation of magic angle spinning NMR spectra of powdered samples. The response of a chemical or biological system to simultaneously applied radio frequency and static or extremely low-frequency magnetic fields could form the basis for a diagnostic test for the operation of the radical pair mechanism that would not require prior knowledge of the nature and properties of the radical reaction.

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PMID: 

Sci Rep. 2017 10 24 ;7(1):13945. Epub 2017 Oct 24. PMID: 29066742

Abstract Title: 

Cardamonin inhibits colonic neoplasia through modulation of MicroRNA expression.

Abstract: 

Colorectal cancer is currently the third leading cause of cancer related deaths. There is considerable interest in using dietary intervention strategies to prevent chronic diseases including cancer. Cardamonin is a spice derived nutraceutical and herein, for the first time we evaluated the therapeutic benefits of cardamonin in Azoxymethane (AOM) induced mouse model of colorectal cancer. Mice were divided into 4 groups of which three groups were given six weekly injections of AOM. One group served as untreated control and remaining groups were treated with either vehicle or Cardamonin starting from the same day or 16 weeks after the first AOM injection. Cardamonin treatment inhibited the tumor incidence, tumor multiplicity, Ki-67 andβ-catenin positive cells. The activation of NF-kB signaling was also abrogated after cardamonin treatment. To elucidate the mechanism of action a global microRNA profiling of colon samples was performed. Computational analysis revealed that there is a differential expression of miRNAs between thesegroups. Subsequently, we extend our findings to human colorectal cancer and found that cardamonin inhibited the growth, induces cell cycle arrest and apoptosis in human colorectal cancer cell lines. Taken together, our study provides a better understanding of chemopreventive potential of cardamoninin colorectal cancer.

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PMID: 

Environ Int. 2011 Jan ;37(1):26-30. PMID: 20619895

Abstract Title: 

The impact of exposure to radio frequency electromagnetic fields on chronic well-being in young people–a cross-sectional study based on personal dosimetry.

Abstract: 

A possible influence of radio frequency electromagnetic field (RF EMF) exposure on health outcomes was investigated in various studies. The main problem of previous studies was exposure assessment. The aim of our study was the investigation of a possible association between RF EMF and chronic well-being in young persons using personal dosimetry. 3022 children and adolescents were randomly selected from the population registries of four Bavarian cities in Germany (participation 52%). Personal interview data on chronic symptoms, socio-demographic characteristics and potential confounders were collected. A 24-h radio frequency exposure profile was generated using a personal dosimeter. Exposure levels over waking hours were expressed as mean percentage of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) reference level. Half of the children and nearly every adolescent owned a mobile phone which was used only for short durations per day. Measured exposure was far below the current ICNIRP reference levels. The most reported chronic symptom in children and adolescents was fatigue. No statistically significant association between measured exposure and chronic symptoms was observed. Our results do not indicate an association between measured exposure to RF EMF and chronic well-being in children and adolescents. Prospective studies investigating potential long-term effects of RF EMF are necessary to confirm our results.

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PMID: 

Mediators Inflamm. 2010 ;2010. Epub 2010 Aug 25. PMID: 20871834

Abstract Title: 

Lipid mediators in acne.

Abstract: 

Multiple factors are involved in acne pathogenesis, and sebum secretion is one of the main ones. The role sebum plays in acne development has not been completely elucidated yet; however, increasing amounts of data seem to confirm the presence of alterations in sebum from acne patients. Altered ratio between saturated and unsaturated fatty acids has been indicated as an important feature to be considered in addition to the altered amount of specific fatty acids such as linoleic acid. Furthermore, particular attention has been focused on squalene peroxide that seems to be able to induce an inflammatory response beyond cytotoxicity and comedones formation. Moreover, recent data suggest that lipid mediators are able to interfere with sebocytes differentiation and sebogenesis through the activation of pathways related to peroxisome proliferators-activated receptors. Understanding the factors and mechanisms that regulate sebum production is needed in order to identify novel therapeutic strategies for acne treatment.

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PMID: 

J Invest Dermatol. 2017 05 ;137(5):1114-1125. Epub 2017 Jan 25. PMID: 28131815

Abstract Title: 

Sebaceous Gland-Rich Skin Is Characterized by TSLP Expression and Distinct Immune Surveillance Which Is Disturbed in Rosacea.

Abstract: 

The microbial community exhibits remarkable diversity on topographically distinct skin regions, which may be accompanied by differences in skin immune characteristics. Our aim was to compare the immune milieu of healthy sebaceous gland-rich (SGR) and sebaceous gland-poor skin areas, and to analyze its changes in an inflammatory disease of SGR skin. For this purpose, immunohistochemical, immunocytochemical, and quantitative real-time PCR analyses of thymic stromal lymphopoietin (TSLP) and other cytokines, phenotypic immune cell markers and transcription factors were carried out in samples from sebaceous gland-poor, SGR skin and from papulopustular rosacea. TSLP mRNA and protein production was also studied in cultured keratinocytes. In SGR skin, higher TSLP expression, dendritic cell appearance without prominent activation, and T cell presence with IL-17/IL-10 cytokine milieu were detected compared with sebaceous gland-poor skin. Linoleic acid, a major sebum component, was found to induce TSLP expression dose-dependently in keratinocytes. In papulopustular rosacea, significantly decreased TSLP level and influx of inflammatory dendritic cells and T cells with IL-17/interferon-γ cytokine milieu were observed. According to our results, SGR skin is characterized by a distinct, noninflammatory immune surveillance, which may explain the preferred localization of inflammatory skin diseases, and can influence future barrier repair therapeutic concepts.

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PMID: 

Immunopharmacol Immunotoxicol. 2018 Apr ;40(2):126-133. Epub 2018 Jan 5. PMID: 29303022

Abstract Title: 

Cardamonin inhibits pro-inflammatory cytokine production and suppresses NO pathway in PBMCs from patients with primary Sjögren's syndrome.

Abstract: 

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with a complex pathophysiology primarily affecting exocrine glands, leading to compromised secretory function. Recent studies imply that many inflammatory mediators, such as pro-inflammatory cytokines and nitric oxide, are critical in the development and perpetuation of pSS systemic manifestations. In the current study, we aimed to investigate the ex vivo immunomodulatory effect of cardamonin (CHO), on pro-inflammatory cytokines, TNF-α, IL-6 and inducible nitric oxide synthase (iNOS) expression during pSS. For this purpose, peripheral blood mononuclear cells isolated from pSS patients and healthy controls were cultured with different concentrations of cardamonin. Cytokine levels were measured by ELISA and NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence staining. Our results suggest that cardamonin inhibits TNF-α, IL-6 and NO production and downregulates iNOS expression and NF-κB activation. Collectively, our results highlight the ex vivo immunomodulatory effects of cardamonin on pro-inflammatory cytokine production and NO pathway in pSS patients. Therefore, cardamonin is a potential candidate for controlling inflammation during pSS.

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PMID: 

Dermatoendocrinol. 2017 ;9(1):e1375636. Epub 2017 Oct 17. PMID: 29484100

Abstract Title: 

Sebaceous-immunobiology is orchestrated by sebum lipids.

Abstract: 

The major role of sebaceous glands in mammals is to produce sebum, which coats the epidermis and the hair providing waterproofing, thermoregulation and photoprotection. However, as the need for these functions decreased along the evolutionary changes in humans, a relevant question has been raised: are sebaceous glands and sebum the remnants of our mammalian heritage or do they have overtaken a far more complex role in human skin biology? Trying to provide answers to this question, this review introduces the evolving field of sebaceous immunobiology and puts into the focus the pathways that sebum lipids use to influence the immune milieu of the skin. By introducing possible modifiers of sebaceous lipogenesis and discussing the – human-specific – alterations in composition and amount of sebum, the attribute of sebum as a sensitive tool, which is capable of translating multiple signalling pathways into the dermal micro environment is presented. Further their interaction with macrophages and keratinocytes involves sebum lipid fractions into disease pathogenesis, which could lead – on the other side – to the development of novel sebum-based therapeutic strategies.

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PMID: 

Oncol Lett. 2018 Mar ;15(3):3991-3997. Epub 2018 Jan 8. PMID: 29456744

Abstract Title: 

Cardamonin enhances the anti-proliferative effect of cisplatin on ovarian cancer.

Abstract: 

The mammalian target of rapamycin (mTOR) is well-known as a promising therapeutic target in various cancer cells. mTOR activation decreases the sensitivity of ovarian cancer to cisplatin. Cardamonin inhibits the proliferation of various cancer cells by mTOR suppression. The present study examined whether cardamonin combined with cisplatin is efficacious for the anti-proliferation of ovarian cancer cells. The anti-proliferative effect was determined by MTT and cell cycle assays. Activation of the mTOR signal pathway and the expression of anti-apoptotic proteins were evaluated by western blot analysis. Cardamonin significantly enhanced the effects of cisplatin on cell proliferation and cell cycle progression. The expression of B cell lymphoma-2, X-linked inhibitor of apoptosis protein and Survivin was significantly decreased following combination treatment. Furthermore, the activation of mTOR and its downstream 70 kDa ribosomal protein S6 kinase was inhibited by cardamonin. These results demonstrated that the combinatorial effects of cardamonin and cisplatin on anti-proliferation were enhanced by suppressing the expression of anti-apoptotic proteins and activation of mTOR in ovarian cancer cells.

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PMID: 

Planta Med. 2018 Nov ;84(16):1183-1190. Epub 2018 May 17. PMID: 29772587

Abstract Title: 

Anti-inflammatory Effects of Cardamonin in Ovarian Cancer Cells Are Mediated via mTOR Suppression.

Abstract: 

Cardamonin exhibits a variety of pharmacological activities including anti-inflammatory and antitumor, which are correlated with the inhibition of nuclear factor-kappaB and the mammalian target of rapamycin, respectively. However, whether the anti-inflammatory effects of cardamonin are mediated by the mammalian target of rapamycin remains unknown. In this study, ovarian cancer SKOV3 cells were cultured with lipopolysaccharide to induce inflammation, and the inhibitory effects and underlying molecular mechanisms of cardamonin were investigated using specific inhibitors of the mammalian target of rapamycin and the nuclear factor-kappaB pathway (rapamycin and pyrrolidine dithiocarbamate, respectively). Our results indicated that cardamonin inhibited the viability of normal and lipopolysaccharide-pretreated SKOV3 cells in a concentration-dependent manner. In accordance with rapamycin, the activation of the mammalian target of rapamycin and its downstream target, ribosomal protein S6 kinase 1, was inhibited by cardamonin, while pyrrolidine dithiocarbamate substantially blocked nuclear factor-kappaB activation and mildly inhibited the phosphorylation of the mammalian target of rapamycin and ribosomal protein S6 kinase 1. Pretreated with pyrrolidine dithiocarbamate, the effect of cardamonin on the mammalian target of rapamycin signalling was not affected, but the expression of inflammatory factors was further reduced. In cells pretreated with rapamycin, the inhibitory effects of cardamonin were completely suppressed with regards to the phosphorylation of the mammalian target of rapamycin, ribosomal protein S6 kinase 1, TNF-, and interleukin-6, and nuclear factor-kappaB p65 protein expression was decreased. In conclusion, our findings indicate that the anti-inflammatory effects of cardamonin are correlated with mammalian target of rapamycin inhibition.

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PMID: 

Oncol Lett. 2018 Jun ;15(6):9641-9646. Epub 2018 Apr 26. PMID: 29928339

Abstract Title: 

Cardamonin reduces chemotherapy resistance of colon cancer cells via the TSP50/NF-κB pathway.

Abstract: 

It has previously been reported that cardamonin is able to regulate glycometabolism and vasodilation whilst also exhibiting anti-inflammatory and antitumor properties. The antitumor effect of cardamonin is multifaceted, and so it is necessary to investigate the antitumor mechanisms of cardamonin at the molecular level. Cardamonin alters chemotherapy-resistant colon cancer cell growth; however, the underlying mechanism is unknown. The present study was conducted to investigate the effect of cardamonin on chemotherapy-resistant colon cancer cells and the possible mechanisms of action. Cardamonin significantly suppressed the growth of chemotherapy-resistant colon cancer cells, induced apoptosis and promoted caspase-3/9 activity and Bax protein expression in 5-fluorouracil (5-FU)-resistant HCT-116 cells. Cardamonin significantly suppressed c-MYC, octamer-binding transcription factor 4, cyclin E, testes-specific protease 50 and nuclear factor-κB protein expression in 5-FU-resistant HCT-116 cells. The findings of the present study demonstrate that cardamonin suppresses chemotherapy-colon cancer cell via the NF-κB pathway.

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