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Hyperinflammation is one of the most important pathophysiological risk factors for poor prognosis in patients with coronavirus disease-2019 (Covid-19). Low vagal neuro-immune modulation can lead into this kind of immune dysregulation. The association between vagal activity, sex and inflammatory markers were investigated in patients with Covid-19. A total of 19 patients with Covid-19 were included in the present study. Vagus nerve activity was indexed by heart rate variability (HRV) derived from electrocardiogram at hospital admission. Linear HRV parameters included the root mean square of successive RR interval differences (RMSSD) and high-frequency HRV (HF-HRV), while non-linear parameters included 2 UV%. Immune/inflammatory parameters included C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil/lymphocyte ratio (NLR), systemic inflammatory index (SII), and procalcitonin (PCT). It has been revealed that both linear HRV indices HF-HRV and RMSSD, are significantly negatively correlated with CRP and IL-6, independent of age. The non-linear index of 2 UV% is significantly negatively correlated with NLR and SII, which reflect subtle changes in the response of immunocompetent cells. Patients that received high-flow nasal oxygen therapy had significantly higher IL-6 and CRP levels and lower levels of HF-HRV and RMSSD. These patients also had a significantly longer length of stay in hospital (LOS) than patients receiving low-flow oxygen therapy. Men had higher plasma PCT levels and longer LOS in hospital than women, and PCT statistically explained (mediated) the association between sex and LOS. The present study showed different correlations of linear and non-linear vagal indexes of HRV and inflammatory markers in patients with Covid-19. Significant sex differences in certain inflammatory markers were also observed, which may very well verify previous findings of poor prognosis in men with Covid-19. HRV reflects a continuous interaction between the sympathetic and parasympathetic autonomic nervous systems, which are affected by mental or physical stress, and certain disease states. The increased sympathetic and decreased parasympathetic vagal tone contribute to a higher risk of diseases associated with inflammation, cardiovascular disease, cancer, pulmonary diseases and other pathologies, including infectious diseases such as Covid-19. The present study showed that higher RMSSD (a marker of vagal activity) in Covid-19 patients is associated with lower levels of inflammatory biomarkers, a lower need for treatment and is negatively correlated with intensive care unit admission, leading to a shorter hospital stay. These findings support the idea that activation of vagus nerve may help certain Covid-19 patients by reducing the cytokine storm and excessive inflammation. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma is one of the most lethal diseases, with an exceptionally poor prognosis. The successful clinical management of strongly related diabetes could significantly contribute to more efficient control of cancer development and progression. In this regard, various natural products have been explored. This review evaluates the therapeutic potential of four natural products (Curcumin—Curcuma longa L.; Thymoquinone—Nigella sativa L.; Genistein—Glycine max L.; Ginkgo biloba L.) and one nutritional intervention, in the form of a low-carbohydrate ketogenic diet in pancreatic cancer and diabetic patients, and discusses their possible integration in supportive cancer management. Although the results have shown their effectiveness in the treatment of diabetes, the therapeutic response and survival time were not significantly improved in pancreatic cancer patients, despite improvements in several biological parameters. Nevertheless, based on published data, the studied natural products and nutritional intervention can potentially become promising therapeutic approaches for pancreatic cancer risk reduction through early intervention at the onset of diabetic complications. The correlation between pancreatic ductal adenocarcinoma (PDAC) and diabetes-related mechanisms support the hypothesis that early therapeutic strategies targeting diabetes can contribute to PDAC risk reduction and treatment improvement. A systematic review was conducted, using PubMed, Embase and Cochrane Library databases, to evaluate the current evidence from clinical studies qualitatively examining the efficacy of four natural products: Curcumin—Curcuma longa L.; Thymoquinone—Nigella sativa L.; Genistein—Glycine max L.; Ginkgo biloba L.; and a low-carbohydrate ketogenic diet in type 2 diabetes (T2D) and PDAC treatment. A total of 28 clinical studies were included, showing strong evidence of inter-study heterogeneity. Used as a monotherapy or in combination with chemo-radiotherapy, the studied substances did not significantly improve the treatment response of PDAC patients. However, pronounced therapeutic efficacy was confirmed in T2D. The natural products and low-carbohydrate ketogenic diet, combined with the standard drugs, have the potential to improve T2D treatment and thus potentially reduce the risk of cancer development and improve multiple biological parameters in PDAC patients. [ABSTRACT FROM AUTHOR]

Triorganotin compounds induce hormonal alterations, i.e., endocrine-disrupting effects in mammals, including humans. Tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPT-Cl) are known to function as nuclear retinoid X receptor (RXR) agonists. Their cytotoxic effects in ER(+) luminal human breast cancer cell line MCF-7 and ER(−) basal-like human breast cancer cell line MDA-MB-231 were examined. We observed significantly higher toxicity of TBT-Cl in comparison with TPT-Cl in both cell lines. Comparable apoptosis-inducing concentrations were 200 and 800 nM, respectively, as shown by PARP cleavage and FDA staining. Both compounds activated executive caspases in the concentration-dependent manner in MDA-MB-231 cells, but the onset of TPT-Cl-induced caspase-3/7 activation was delayed in comparison with TBT-Cl. Both compounds slowed down the migration of these highly invasive cells, which was accompanied by RARbeta upregulation. Other RAR and RXR expressions were differentially modulated by studied organotins in both cell lines. [ABSTRACT FROM AUTHOR]

Cisplatin resistance is one of the major obstacles in the treatment of ovarian cancer. In an effort to look for new possibilities of how to overcome this difficulty, we studied the mechanisms of the interactions between sulforaphane (SFN) and cisplatin (cisPt) in combined treatment of human ovarian carcinoma A2780 and SKOV3 cell lines. Synergy (A2780) and antagonism (SKOV3) found in MTT assay was confirmed by apoptosis. While SFN significantly potentiated cisPt-induced DNA damage in A2780 cells, it protected SKOV3 cells against cisPt-crosslinking. We revealed a less efficient Nrf-2 pathway inducibility by SFN in A2780 compared to SKOV3 cells, when activation of the Nrf-2 pathway incites its protectivity against cisPt. Thus, different activation of the Nrf-2 pathway may explain the dual effects of SFN. [ABSTRACT FROM AUTHOR]

The development and progression of cancer depends on both tumor micro- and macroenvironments. In addition, psychosocial and spiritual "environments" might also affect cancer. It has been found that the nervous system, via neural and humoral pathways, significantly modulates processes related to cancer at the level of the tumor micro- and macroenvironments. The nervous system also mediates the effects of psychosocial and noetic factors on cancer. Importantly, data accumulated in the last two decades have clearly shown that effects of the nervous system on cancer initiation, progression, and the development of metastases are mediated by the sympathoadrenal system mainly via β-adrenergic receptor signaling. Here, we provide a new complex view of the role of β-adrenergic receptor signaling within the tumor micro- and macroenvironments as well as in mediating the effects of the psychosocial and spiritual environments. In addition, we describe potential preventive and therapeutic implications. [ABSTRACT FROM AUTHOR]

The cytotoxicity of two recently synthesized triorganotin isothiocyanate derivatives, nuclear retinoid X receptor ligands, was tested and compared in estrogen-receptor-positive MCF 7 and -negative MDA-MB-231 human breast carcinoma cell lines. A 48 h MTT assay indicated that tributyltin isothiocyanate (TBT-ITC) is more cytotoxic than triphenyltin isothiocyanate (TPT-ITC) in MCF 7 cells, and the same trend was observed in the MDA-MB-231 cell line. A comet assay revealed the presence of both crosslinks and increasing DNA damage levels after the 17 h treatment with both derivatives. Differences in cytotoxicity of TBT-ITC and TPT-ITC detected by FDA staining correspond to the MTT data, communicating more pronounced effects in MCF 7 than in the MDA-MB-231 cell line. Both derivatives were found to cause apoptosis, as shown by the mitochondrial membrane potential (MMP) depolarization and caspase-3/7 activation. The onset of caspase activation correlated with MMP dissipation and the total cytotoxicity more than with the amount of active caspases. In conclusion, our data suggest that the DNA damage induced by TBT-ITC and TPT-ITC treatment could underlie their cytotoxicity in the cell lines studied. [ABSTRACT FROM AUTHOR]

The study focused on protective potential of phytochemicals applicable in prevention and health protection is of great importance. Various structures of these compounds and a wide range of their biological activities have inspired organic chemists to sythesize their effective analogues in order to further increase their efficacy. The aims of our study were (i) to synthesize phenylethanoid glycopyranosides: salidroside (SALI - tyrosol β- d -glucopyranoside), tyrosol β- d -galactopyranoside (TYBGAL), tyrosol α- d -galactopyranoside (TYAGAL), tyrosol α- d -mannopyranoside (TYAMAN), hydroxytyrosol α- d -mannopyranoside (HOTAMA), homosyringyl β- d -glucopyranoside (HSYGLU), hydroxytyrosol β- d -xylopyranoside (HOTXYL) and hydroxysalidroside (HOSALI); (ii) to determine their antioxidant capacities (cell-free approaches); (iii) to evaluate their cytotoxicity (MTT test), protectivity against hydrogen peroxide (H 2 O 2 ; comet assay) and effect on the intracellular glutathione level (iGSH; flow cytometry) in experimental system utilizing human hepatoma HepG2 cells. HOSALI, HOTAMA, HOTXYL and HSYGLU manifested the highest antioxidant capacity in cell-free assays and they were most active in protection of HepG2 cells against H 2 O 2. On the other hand, pre-treatment of HepG2 cells with SALI had protective effects even though SALI displayed almost no activity in cell-free assays. Differences in the efficacy of the analogues revealed that structures of their molecules in terms of aglycone combined with sugar moiety affect their activities. • Prepared phenylethanoid glycopyranosides exhibit different extent of antioxidant and DNA-protective capacities. • Hydroxytyrosol and homosyringyl glycosides show the best antioxidant parameters in cell-free tests used. • Hydroxysalidroside protects plasmid DNA against Fe2+-induced damage at all concentrations tested. • Hydroxytyrosol and homosyringyl glycosides are most active in HepG2 cells protection against H 2 O 2. • Salidroside protects HepG2 cells against H 2 O 2 , without displaying antioxidant activity. [ABSTRACT FROM AUTHOR]

Background/aim: Triple-negative breast cancer (TNBC) constitutes 15-20% of all breast carcinomas, affecting younger women more often and has a worse prognosis than other types of breast cancer, due to the combination of more aggressive clinical behavior and lack of molecular targets for therapy. This study assessed the effects of non-genotoxic concentrations of tributyltin isothiocyanate (TBT-ITC) and triphenyltin isothiocyanate (TPT-ITC) on MDA-MB-231 cells., Materials and Methods: MTT assay, comet assay, kinetic imaging and flow cytometry were used for analysis of MDA-MB-231 cells., Results: The results showed that 100 nM concentration of TBT-ITC and TPT-ITC, that did not affect viability or DNA integrity, slowed-down migration by CD44 down-regulation. Moreover, both compounds demonstrated immunomodulatory properties, attenuating PD-L1 expression in MDA-MB-231 cells., Conclusion: TPT-ITC was more effective in down-regulating CD44 expression and reducing migration than TBT-ITC, while TBT-ITC was more potent in lowering PD-L1 expression in comparison with TPT-ITC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The aim of our prospective, interventional, pre-post, single arm study was to supplement the lack of knowledge of the effect of short-term Pilates intervention on selected blood parameters of healthy women. Female volunteers were recruited for 2-weeks Pilates intervention. Blood has been collected and anthropometric parameters were measured before and after exercise period (EP). Plasma insulin, cortisol, and dehydroepiandrosterone sulphate levels, erythrocyte antioxidant activity, glutathione levels, NK cytotoxicity and plasma cytokines were analysed. We found a decrease in erythrocyte antioxidant enzymes SOD and GPx activity; GSH levels; in the pro-inflammatory chemokine MCP-1 and trend to reduction in MIP-1β, PDGF and VEGF levels in plasma. NK cell cytotoxic activity increased after Pilates EP in the percentage of specific lysis at 25:1 effector: target (E:T) ratio and the same trend was observed at all E:T ratios as well as in the amount of lytic units per 107 cells. Our findings show that Pilates exercise may improve NK cell immune response and inflammatory milieu in plasma of healthy women.

Triorganotin compounds induce hormonal alterations, i.e., endocrine-disrupting effects in mammals, including humans. Tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPT-Cl) are known to function as nuclear retinoid X receptor (RXR) agonists. Their cytotoxic effects in ER(+) luminal human breast cancer cell line MCF-7 and ER(-) basal-like human breast cancer cell line MDA-MB-231 were examined. We observed significantly higher toxicity of TBT-Cl in comparison with TPT-Cl in both cell lines. Comparable apoptosis-inducing concentrations were 200 and 800 nM, respectively, as shown by PARP cleavage and FDA staining. Both compounds activated executive caspases in the concentration-dependent manner in MDA-MB-231 cells, but the onset of TPT-Cl-induced caspase-3/7 activation was delayed in comparison with TBT-Cl. Both compounds slowed down the migration of these highly invasive cells, which was accompanied by RARbeta upregulation. Other RAR and RXR expressions were differentially modulated by studied organotins in both cell lines.