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Simple Summary: Long non-coding RNAs (lncRNAs) exert their influence on transcriptional regulation and genome organization by associating with transcription factors, chromatin, RNAs and various proteins. In particular, studies have established a widespread involvement of cross-talks between lncRNAs and nuclear receptors (NRs) in pathology of diseases such as cancer. A deeper understanding of these cross-talks will not only help gain greater insights into cancer physiology, but also guide the development for newer and improved therapeutic strategies aimed at cancer. Long non-coding RNAs (lncRNAs) play key roles in various epigenetic and post-transcriptional events in the cell, thereby significantly influencing cellular processes including gene expression, development and diseases such as cancer. Nuclear receptors (NRs) are a family of ligand-regulated transcription factors that typically regulate transcription of genes involved in a broad spectrum of cellular processes, immune responses and in many diseases including cancer. Owing to their many overlapping roles as modulators of gene expression, the paths traversed by lncRNA and NR-mediated signaling often cross each other; these lncRNA-NR cross-talks are being increasingly recognized as important players in many cellular processes and diseases such as cancer. Here, we review the individual roles of lncRNAs and NRs, especially growth factor modulated receptors such as androgen receptors (ARs), in various types of cancers and how the cross-talks between lncRNAs and NRs are involved in cancer progression and metastasis. We discuss the challenges involved in characterizing lncRNA-NR associations and how to overcome them. Furthering our understanding of the mechanisms of lncRNA-NR associations is crucial to realizing their potential as prognostic features, diagnostic biomarkers and therapeutic targets in cancer biology. [ABSTRACT FROM AUTHOR]

Flavonoids are polyphenolic phytochemicals, which occur naturally in plants and possess both anti-oxidant and pro-oxidant properties. Flavonoids are gaining increasing popularity in the pharmaceutical industry as healthy and cost-effective compounds. Flavonoids show beneficial pharmacological activities in the treatment and prevention of various types of diseases. They are natural and less toxic agents for cancer chemotherapy and radiotherapy via regulation of multiple cell signaling pathways and pro-oxidant effects. In this review, we have summarized the mechanisms of action of selected flavonoids, and their pharmacological implications and potential therapeutic applications in cancer therapy. [ABSTRACT FROM AUTHOR]

Purpose: Radiobiological research continues to focus on finding newer strategies for enhanced killing of tumor cells by ionizing radiation. In recent years, chemotherapeutic drugs have been found to possess the capabilities to sensitize tumor cells without affecting the normal cells. There have been increasing research efforts to identify novel and nontoxic compounds which cause minimal or no harm to normal cells but maximize tumor toxicity response to radiation exposure. Extensive researches on flavonoids that are compounds derived from plants have shown that these have promising abilities as radioprotectors and radiosensitizers. Conclusions: In this review, we examine the role of flavonoids as potential radiosensitizers, review the underlying molecular mechanisms and discuss their potential usefulness in improving cancer radiotherapy. It is emphasized that obtaining a deeper insight into the molecular mechanisms underlying the combined action of flavonoids and ionizing radiation may provide new directions for radiobiological research applicable to the much needed enhanced selective tumor cytotoxicity to treatment agents. [ABSTRACT FROM AUTHOR]

Byline: Prabha Tiwari, S. Balakrishnan, S. Kannan, H.S. Kushwaha, K.P. Mishra The major biological consequences of ionising radiation are generally attributed to the generated free radicals and their reactions with vital cellular components. The level of antioxidants in irradiated cells and animals is generally considered an important determinant of radiobiological damage. The present study aimed to investigate the effect of antioxidants of the thiol family, namely, N-acetyl cysteine (NAC), glutathione (GSH) and thioproline (TP) on the radiation-induced chromosomal damage in human lymphocytes in vitro. The incidence of micronucleus (MN) formation, as measured by the cytochalasin B method, was found to be dependent on low to moderate radiation doses (0-200 cGy). The frequency of MN formation in lymphocytes pretreated with antioxidants was found to decrease with their concentration (100-300 μM). The results show that GSH was a more effective protector than NAC or TP, possibly due to relative radical scavenging efficiency. It was further found that treatment with equimolar concentrations of combined NAC and GSH yielded the most effective reduction in MN frequency compared to other combinations of NAC-TP and GSH-TP. The results suggest that the pretreatment of blood with thiol antioxidants significantly prevented MN formation in the isolated lymphocytes. These results may help in developing protocols for effective protectors against radiation exposure for practical applications.

Coconut oil is used as a dietary oil worldwide, and its healthy effects are recognized by the fact that coconut oil is easy to digest, helps in weight management, increases healthy cholesterol, and provides instant energy. Although topical application of coconut oil is known to reduce skin infection and inflammation, whether dietary coconut oil has any role in decreasing skin inflammation is unknown. In this study, we showed the impact of dietary coconut oil in allergic skin inflammation by using a mouse model of contact hypersensitivity (CHS). Mice maintained on coconut oil showed amelioration of skin inflammation and increased levels of cis‐5, 8, 11‐eicosatrienoic acid (mead acid) in serum. Intraperitoneal injection of mead acid inhibited CHS and reduced the number of neutrophils infiltrating to the skin. Detailed mechanistic studies unveiled that mead acid inhibited the directional migration of neutrophils by inhibiting the filamentous actin polymerization and leukotriene B4 production required for secondary recruitment of neutrophils. Our findings provide valuable insights into the preventive roles of coconut oil and mead acid against skin inflammation, thereby offering attractive therapeutic possibilities. [ABSTRACT FROM AUTHOR]

Abstract: We previously demonstrated that though the human SAA1 gene shows no typical STAT3 response element (STAT3-RE) in its promoter region, STAT3 and the nuclear factor (NF-κB) p65 first form a complex following interleukin IL-1 and IL-6 (IL-1+6) stimulation, after which STAT3 interacts with a region downstream of the NF-κB RE in the SAA1 promoter. In this study, we employed a computational approach based on indirect read outs of protein–DNA contacts to identify a set of candidates for non-consensus STAT3 transcription factor binding sites (TFBSs). The binding of STAT3 to one of the predicted non-consensus TFBSs was experimentally confirmed through a dual luciferase assay and DNA affinity chromatography. The present study defines a novel STAT3 non-consensus TFBS at nt −75/−66 downstream of the NF-κB RE in the SAA1 promoter region that is required for NF-κB p65 and STAT3 to activate SAA1 transcription in human HepG2 liver cells. Our analysis builds upon the current understanding of STAT3 function, suggesting a wider array of mechanisms of STAT3 function in inflammatory response, and provides a useful framework for investigating novel TF-target associations with potential therapeutic implications. [Copyright &y& Elsevier]

Silibinin, a natural flavonoid, under phase I/II clinical trial in prostate cancer patients was aimed to evaluate its chemotherapeutic potential in human breast cancer cell MCF7 and T47D. Results showed that T47D cells were found to be more sensitive to silibinin than MCF7 as observed by proliferation, clonogenic, and apoptotic assays, which was abrogated by pan-caspase inhibitor but remained unaffected by p53 inhibitor. Apoptotic events in both cell types differ temporally and also by magnitude that involved mitochondrial and caspase-8 activation pathway. These results have relevance in understanding silibinin treatment to breast tumor. [ABSTRACT FROM AUTHOR]

Purpose: With increasing utilisation of nuclear technologies in power production, medical and industrial applications, and in a scenario of nuclear terrorism/war, there is an enhanced likelihood of accidental radiation exposure to occupational workers, patients and public. The consequent health effects of the radiation exposure are resultant of interaction of radiation with biological systems and subsequent radiation injury. The present review discusses the knowledge gained in radiation biology that can be exploited for better treatment and management of radiation accident victims. Results: In comparison with planned radiation exposure during diagnosis/therapy, the management of accidental radiation exposure is quite complicated due to uncertainties in dose, duration, organs involved and radionuclides internalised, and hence, require multi-faceted approaches. However, the options available for dosimetry, decorporation of radionuclides and therapeutic protocols of patients are limited, which provides substantial scope in these areas of research. Moreover, there is a need to fill the gaps in knowledge of radiation action in different dose ranges and post-irradiation windows, which would help in improving therapeutic approaches. Cytogenetic approaches are ‘gold standard’ for biodosimetry but with limited applications in mass casualty scenario. State-of-the-art technological advancement and high throughput in metabolomics, proteomics and genomics could be employed successfully in developing better biodosimetry for triage in accidental radiation exposure. Furthermore, identification of targets at organs/organelles level of internalised radionuclides would be helpful to develop effective decorporation strategies. Despite substantial research investigating several agents, which could modify radiation effects, only a few could reach up to practical application due to poor bioavailability or toxicity. Conclusions: Deeper insight into the mechanisms of radiation injury under accidental radiation conditions would be helpful in achieving better biodosimetry, decorporation strategies and improvement in prevention/post-irradiation management of radiation accident patients. [ABSTRACT FROM AUTHOR]

Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here explored the postbiotic potential of two omega-3 α-linolenic acid-derived metabolites: trans -10- cis -15-octadecadienoic acid (t10,c15-18:2) and cis -9- cis -15-octadecadienoic acid (c9,c15-18:2). Dietary intake of lipids rich in omega-3 α-linolenic acid elevated levels of t10,c15-18:2 and c9,c15-18:2 in the serum and feces of mice, an effect dependent on the presence of intestinal bacteria. Notably, t10,c15-18:2 mitigated skin inflammation in mice that became hypersensitive after exposure to 2,4-dinitrofluorobenzene, an experimental model for allergic contact dermatitis. In particular, t10,c15-18:2-but not c9,c15-18:2-attenuated ear swelling and edema, characteristic symptoms of contact hypersensitivity. The anti-inflammatory effects of t10,c15-18:2 were due to its ability to suppress the release of vascular endothelial growth factor A from keratinocytes, thereby mitigating the enhanced vascular permeability induced by hapten stimulation. Our study identified retinoid X receptor as a functional receptor that mediates the downregulation of skin inflammation upon treatment with t10,c15-18:2. Our results suggest that t10,c15-18:2 holds promise as an omega-3 fatty acid-derived postbiotic with potential therapeutic implications for alleviating the skin edema seen in allergic contact dermatitis-induced inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Saika, Nagatake, Kishino, Kitamura, Honda, Hosomi, Tiwari, Node, Kawai, Kondo, Ishida, Kabashima, Ogawa and Kunisawa.)

Retinol is widely used in topical skincare products to ameliorate skin aging and treat acne and wrinkles; however, retinol and its derivatives occasionally have adverse side effects, including the induction of irritant contact dermatitis. Previously, we reported that mead acid (5,8,11-eicosatrienoic acid), an oleic acid metabolite, ameliorated skin inflammation in dinitrofluorobenzene-induced allergic contact hypersensitivity by inhibiting neutrophil infiltration and leukotriene B 4 production by neutrophils. Here, we showed that mead acid also suppresses retinol-induced irritant contact dermatitis. In a murine model, we revealed that mead acid inhibited keratinocyte abnormalities such as keratinocyte hyperproliferation. Consistently, mead acid inhibited p38 MAPK (mitogen-activated protein kinase) phosphorylation, which is an essential signaling pathway in the keratinocyte hyperplasia induced by retinol. These inhibitory effects of mead acid were associated with the prevention of both keratinocyte hyperproliferation and the gene expression of neutrophil chemoattractants, including Cxcl1 and Cxcl2, and they were mediated by a PPAR (peroxisome proliferator-activated receptor)-α pathway. Our findings identified the anti-inflammatory effects of mead acid, the use of which can be expected to minimize the risk of adverse side effects associated with topical retinoid application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Saika, Tiwari, Nagatake, Node, Hosomi, Honda, Kabashima and Kunisawa.)

Dietary intake of ω3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid is beneficial for health control. We recently identified 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) as a lipid metabolite endogenously generated from eicosapentaenoic acid that exhibits potent anti-allergic and anti-inflammatory properties. However, chemically synthesized 17,18-EpETE is enantiomeric due to its epoxy group-17( S ),18( R )-EpETE and 17( R ),18( S )-EpETE. In this study, we demonstrated stereoselective differences of 17( S ),18( R )-EpETE and 17( R ),18( S )-EpETE in amelioration of skin contact hypersensitivity and found that anti-inflammatory activity was detected in 17( S ),18( R )-EpETE, but not in 17( R ),18( S )-EpETE. In addition, we found that cytochrome P450 BM-3 derived from Bacillus megaterium stereoselectively converts EPA into 17( S ),18( R )-EpETE, which effectively inhibited the development of skin contact hypersensitivity by inhibiting neutrophil migration in a G protein-coupled receptor 40-dependent manner. These results suggest the new availability of a bacterial enzyme to produce a beneficial lipid mediator, 17( S ),18( R )-EpETE, in a stereoselective manner. Our findings highlight that bacterial enzymatic conversion of fatty acid is a promising strategy for mass production of bioactive lipid metabolites., Competing Interests: There are no conflict of interest to declare., (© 2019 The Authors.)

The aim of the present study is to determine the dose distribution in gamma irradiation chambers by chemical dosimetry and to establish its correlation with biological dosimetry. The dose-distribution studies of these two gamma chambers show that compared to the center point of the chambers, the dose rate was 17%-22% higher at the circumference. Moreover, the dose rate was 12%-18% lower at the bottom and top positions compared to the center point. It was interesting to observe that the dose rate determined by chemical dosimetry was well correlated with the number of micro-nucleus (MN) formations at different positions of the chamber. Our results suggest that the formation of the single MN/cell was better correlated with the dose rate than the double MN/cell, suggesting that the number of single MN/cells could be better biomarkers for determining the dose rate. These results provide a correlation between chemical and biological dosimetry, which may have relevance in the development of better bioassay techniques for radiation exposure.