At the heart of the matter: Cardiovascular health challenges among incarcerated women.

Many factors appear to contribute to an increased risk for cardiovascular disease (CVD) among incarcerated women. Imprisonment is associated with a bodyweight gain and an increased prevalence of overweight and obesity. Inadequate physical activity and unhealthy nutrition further contribute to this positive energy balance. Classical CVD risk factors are common, including hypertension, diabetes mellitus, metabolic syndrome, and smoking. Moreover, imprisonment is associated with an increased incidence of mental health issues, such as depression and anxiety, with coping mechanisms, including substance abuse, being frequently adopted. Specific attitudes in the correctional environment, including hunger strikes, bullying, abuse and solitary confinement, are effectors of cardiovascular and mental ill-health. Furthermore, the plethora of psychological stressors induces an accelerated aging process, paired with CVD risk. Communicable diseases, mainly human immunodeficiency virus, opportunistic infections and inadequate sunlight exposure increase cardiovascular dysregulation. Health care needs associated with the female sex are not always met, adding to the frustration and compromised well-being. All these factors act independently and cumulatively, increasing CVD risk among incarcerated women.

Novel polycarboxylated EDTA-type cyclodextrins as ligands for lanthanide binding: study of their luminescence, relaxivity properties of Gd(iii) complexes, and PM3 theoretical calculations.

Novel -type cyclodextrin (CD) derivatives, , and , bearing 6, 7 and 8 bis(carboxymethyl)amino (iminodiacetic acid) groups, respectively, were prepared, and their complexation with Eu(iii), Tb(iii) and Gd(iii) ions was studied. Luminescence titrations and mass spectrometry showed formation of multimetal complexes ( 2 to 3, mainly 3 and exactly 4 metal ions), whereas luminescence lifetime measurements revealed the presence of exchangeable water molecules. Semiempirical quantum mechanical calculations, performed by the PM3 method and assessed by DFT calculations on model ligands, indicated efficient multi-metal complexation, in agreement with the experiment. The structures showed coordination of the metal ions in the outer primary side of the CDs via 4 carboxylate O atoms, 2 N atoms and a glucopyranose O atom per metal ion. Coordination of water molecules was also predicted, in accordance with experimental results. Calculated bond lengths and angles were in agreement with literature experimental values of lanthanide complexes. Calculated energies showed that complex stability decreases in the order > > . (1)H NMR molecular relaxivity measurements for the Gd(iii) complexes of , or in water afforded values 4 to 10 times higher than the relaxivity of a commercial contrast agent at 12 MHz, and 6 to 20 times higher at 100 MHz. Solutions of and Gd(iii) complexes in human blood plasma displayed relaxivity values at 100 MHz 7 and 12 times, respectively, higher than the commercial agent. MTT tests of the Gd(iii) complexes using human skin fibroblasts did not show toxicity. Attempts to supramolecularly sensitize the luminescence of the lanthanide complexes using various aromatic CD guests were ineffective, evidently due to large guest-metal distances and inefficient inclusion. The described lanthanide complexes, could be useful as contrast agents in MRI.

Association Between Serum Lipid Levels in Greek Children with Dyslipidemia and Mediterranean Diet Adherence, Dietary Habits, Lifestyle and Family Socioeconomic Factors.

Background: Childhood dyslipidemia is an important risk factor for developing cardiovascular disease in adulthood. Our study aimed to investigate a possible correlation between nutritional, lifestyle, behavioral and socioeconomic factors and serum lipid levels in children with dyslipidemia. Methods: In this retrospective, observational study, in 31 children with dyslipidemia, aged 3-14 years, dietary habits, physical activity, hours watching television or playing video games, family's socioeconomic status, weight of children and parents, and duration of breastfeeding were recorded. The children's adherence to the Mediterranean diet was also evaluated by KidMed index. Statistical analysis was performed using SPSS.22. Results: Children with increased physical activity had lower triglyceride levels, compared to those with lower physical activity (p = 0.001). Children who consumed only one meal per day, had increased levels of total cholesterol (p = 0.01), LDL-cholesterol (p = 0.01), ApoB (p = 0.001) and lipoprotein (a) (p=0.018), compared to those who consumed more than 3 meals per day (p < 0.05). Children who were breastfed less than 6 months had significantly increased LDL-C levels (p = 0.022), compared to children who were breastfed more than 6 months. All other parameters investigated did not differ significantly. Conclusions: This study showed association between lipid profile of children with dyslipidemia and specific nutritional and socioeconomic factors, such as increased physical activity, increased meals consumption during the day, and exclusive breastfeeding for more than 6 months. Nevertheless, further research is needed, in order to confirm these findings.

Methodological quality of clinical practice guidelines for nutrition and weight gain during pregnancy: a systematic review.

CONTEXT: Ensuring a healthy pregnancy and achieving optimal gestational weight gain (GWG) are important for maternal and child health. Nevertheless, the nutritional advice provided during pregnancy is often conflicting, suggesting limited adherence to clinical practice guidelines (CPGs). OBJECTIVE: The aim of this review was to identify all CPGs on maternal nutrition and GWG and to critically appraise their methodological quality. DATA SOURCES: The MEDLINE/PubMed, Cochrane, Guidelines International Network, and BMJ Best Practice databases, along with gray literature, were searched from inception until February 2019 for CPGs and consensus, position, and practice papers. STUDY SELECTION: Clinical practice guidelines published in English and containing advice on maternal nutrition or GWG were eligible. DATA EXTRACTION: Two authors independently extracted data on items pertaining to maternal nutrition or GWG, and CPGs were appraised using the AGREE II instrument. RESULTS: Twenty-two CPGs were included. All scored adequately in the "scope" domain, but most were considered inadequate with regard to stakeholder involvement, rigor of development, applicability, and editorial independence. Many CPGs lacked patient or dietician involvement, and more than half did not disclose funding sources or conflicts of interest. Guidance on GWG was based mostly on Institute of Medicine thresholds, while nutrition recommendations appeared scattered and heterogeneous. CONCLUSION: Despite the importance of maternal nutrition and the plethora of advising bodies publishing relevant guidance, there is room for substantial improvement in terms of development standards and content of nutritional recommendations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42019120898.

Elk-1 associates with FAK, regulates the expression of FAK and MAP kinases as well as apoptosis in HK-2 cells.

Focal adhesion kinase (FAK), MAP kinases and the nuclear transcription factor Elk-1 have been reported to be implicated in the same cellular processes, however, their direct or indirect interaction and potential function(s) has not been documented. Here, we explored the association of FAK with Elk-1, the implication of Elk-1 in the regulation of FAK and MAP kinases expression as well as apoptosis, in HK-2 cells. Biochemical and immunofluorescence approaches strongly support the association of low molecular weight protein bands, recognized by FAK antibodies, with Elk-1 or p(ser383)Elk-1. The FAK/Elk-1 complex is found, mainly, in the cytoplasm, near the nuclear membrane periphery, raising the possibility that Elk-1 may have alternative extranuclear function(s) in HK-2 cells. Furthermore, we demonstrated that Elk-1 siRNA-mediated knockdown experiments, increased apoptosis. By contrast, Elk-1 siRNA decreased significantly the expression of FAK and MAP kinases, supporting the hypothesis that Elk-1 may act as a potential physiological substrate and regulator of FAK and MAP kinases expression. These results strongly support that Elk-1 protein is a novel binding-protein partner for FAK, a finding that significantly broadens the potential functioning of FAK and Elk-1.

Innate immunity in insects: surface-associated dopa decarboxylase-dependent pathways regulate phagocytosis, nodulation and melanization in medfly haemocytes.

Phagocytosis, melanization and nodulation in insects depend on phenoloxidase (PO) activity. In this report, we demonstrated that these three processes appear to be also dependent on dopa decarboxylase (Ddc) activity. Using flow cytometry, RNA interference, immunoprecipitation and immunofluorescence, we demonstrated the constitutive expression of Ddc and its strong association with the haemocyte surface, in the medfly Ceratitis capitata. In addition, we showed that Escherichia coli phagocytosis is markedly blocked by small interfering RNA (siRNA) for Ddc, antibodies against Ddc, as well as by inhibitors of Ddc activity, namely carbidopa and benzerazide, convincingly revealing the involvement of Ddc activity in phagocytosis. By contrast, latex beads and lipopolysaccharide (LPS) did not require Ddc activity for their uptake. It was also shown that nodulation and melanization processes depend on Ddc activation, because antibodies against Ddc and inhibitors of Ddc activity prevent haemocyte aggregation and melanization in the presence of excess E. coli. Therefore, phagocytosis, melanization and nodulation depend on haemocyte-surface-associated PO and Ddc. These three unrelated mechanisms are based on tyrosine metabolism and share a number of substrates and enzymes; however, they appear to be distinct. Phagocytosis and nodulation depend on dopamine-derived metabolite(s), not including the eumelanin pathway, whereas melanization depends exclusively on the eumelanin pathway. It must also be underlined that melanization is not a prerequisite for phagocytosis or nodulation. To our knowledge, the involvement of Ddc, as well as dopa and its metabolites, are novel aspects in the phagocytosis of medfly haemocytes.

Elk-1 is a novel protein-binding partner for FAK, regulating phagocytosis in medfly hemocytes.

Focal adhesion kinase (FAK) and its downstream signaling targets, mitogen-activated protein kinase (MAPKs), are implicated in the process of phagocytosis by insect hemocytes. The goal of this study was to explore further the signaling pathways underlining the process of phagocytosis. The combination of bioinformatics, biochemical, and immunofluorescence approaches strongly support the expression of Elk-1-like protein in medfly hemocytes. Elk-1 is phosphorylated in E. coli or latex beads-challenged hemocytes and osmotic loading experiments as well as flow cytometry analysis demonstrated that Elk-1-like protein regulates the uptake of bacteria. RNA interference (RNAi) and pharmacological inhibitors show that the signaling for Elk-1 phosphorylation is transmitted via FAK/Src and MAPKs pathways. Furthermore, confocal analysis clearly shows that FAK and the phosphorylated FAK at Y397 are localized in the nucleus and cytoplasm, whereas, the phosphorylated Elk-1-like protein is exclusively localized in the nucleus. Finally, co-immunoprecipitation and reciprocal co-immunoprecipitation analysis demonstrated the association of low molecular weight protein bands recognized by FAK antibodies, with Elk-1 or phospho-Elk-1 at ser 383 and confocal microscopy specifies that this association occurs only in the nucleus. These results are strongly supporting that Elk-1-like protein is a novel protein-binding partner for FAK, a finding that significantly broadens the potential functioning of FAK and Elk-1 generally. Evidently, the complex participates in the process of phagocytosis in medfly hemocytes.

Positively charged cyclodextrins as effective molecular transporters of active phosphorylated forms of gemcitabine into cancer cells.

Positively charged cyclodextrins (PCCDs) are molecular carriers of particular interest for their ability to readily enter into cancer cells. Of main interest, guanidino- and aminoalkyl- PCCDs can be conveniently synthesized and form stable and strong inclusion complexes with various active molecules bearing phosphate groups. We have addressed here the challenge to deliver into cancer cells phosphorylated gemcitabine drugs well known for their instability and inability to permeate cell membranes. NMR data corroborated by semiempirical theoretical calculations have shown that aminoalkyl-CDs form sufficiently stable complexes with both mono- and tri-phosphate forms of gemcitabine by simple mixing of the compounds in aqueous solution at physiological pH. Confocal microscopy and radioactivity counting experiments revealed that the developed systems enabled phosphorylated gemcitabine to penetrate efficiently into aggressive human breast cancer cells (MCF7), eventually leading to a substantial reduction of IC50 values. Moreover, compared to free drugs, phosphorylated metabolites of gemcitabine encapsulated in PCCDs displayed improved in vitro activities also on the aggressive human cancer cells CCRF-CEM Ara-C/8 C, a nucleoside transport-deficient T leukemia cell line. The current study offers the proof-of-principle that phosphorylated nucleoside drugs could be efficiently transported by PCCDs into cancer cells.

MAP kinases mediate phagocytosis and melanization via prophenoloxidase activation in medfly hemocytes.

E. coli phagocytosis by medfly hemocytes, in contrast to mammalian macrophages, associates with E. coli-challenged hemocyte secretion by mitogen activating protein (MAP) kinases. In the present work, we examined whether this system links with the proteolytic activation of prophenoloxidase (proPO). ProPO and prophenoloxidase-activating proteinases (PAPs) were initially identified within freshly isolated medfly hemocytes. Moreover, flow cytometry and immunocytochemical analysis revealed the constitutive expression of proPO and its stable association with hemocyte surface. The expression level of hemocyte surface proPO is not affected by E. coli infection. In addition, flow cytometry analysis in freshly isolated hemocytes showed that E. coli phagocytosis is markedly blocked by antibodies against proPO or PAPs, as well as by several serine protease inhibitors, strongly supporting the involvement of proPO cascade in the phagocytosis process. Similarly, it was shown that melanization process depends on proPO activation. MAP kinases appeared to control both phagocytosis and melanization, since they regulate PAPs secretion, a prerequisite for the conversion of proPO to active PO. From this and previous studies, hemocytes appear to be central to immune response in medfly.

Uptake of LPS/E. coli/latex beads via distinct signalling pathways in medfly hemocytes: the role of MAP kinases activation and protein secretion.

In response to LPS/E. coli treatment, extracellular signal-regulated kinase (ERK) is activated in medfly hemocytes. To explore the molecular mechanisms underlying LPS/E. coli/latex beads endo- and phagocytosis, we studied the signalling pathways leading to p38 and c-jun N-terminal kinase (JNK) activation. JNK and p38-like proteins were initially identified within medfly hemocytes. Flow cytometry analysis revealed that mitogen-activated protein kinases (MAPK) are required for phagocytosis. Inhibition of specific MAPK signalling pathways, with manumycin A, toxin A, cytochalasin D and latrunculin A, revealed activation of p38 via Ras/Rho/actin remodelling pathway and activation of JNK that was independent of actin cytoskeleton reorganization. ERK and p38 pathways, but not JNK, appeared to be involved in LPS-dependent hemocyte secretion, whereas all MAPK subfamilies seemed to participate in E. coli-dependent secretion. In addition, flow cytometry experiments in hemocytes showed that the LPS/E. coli-induced release was a prerequisite for LPS/E. coli uptake, whereas latex bead phagocytosis did not depend on hemocyte secretion. This is a novel aspect, as in mammalian monocytes/macrophages LPS/E. coli-triggered release has not been yet correlated with phagocytosis. It is of interest that these data suggest distinct mechanisms for the phagocytosis of E. coli and latex beads in medfly hemocytes.

Efficient "green" encapsulation of a highly hydrophilic anticancer drug in metal-organic framework nanoparticles.

Metal-organic frameworks (MOFs) are coordination polymers of interest for biomedical applications. Of particular importance, nanoparticles made of iron(III) trimesate (MIL-100, MIL standing for Material Institut Lavoisier) (nanoMOFs) can be conveniently synthesised under mild and green conditions. They were shown to be biodegradable, biocompatible and efficient to encapsulate a variety of active molecules. We have addressed here the challenges to encapsulate a highly hydrophilic anticancer prodrug, phosphated gemcitabin (Gem-MP) known for its instability and inability to bypass cell membranes. MIL-100 nanoMOFs acted as efficient "nanosponges", soaking Gem-MP from its aqueous solution with almost perfect efficiency (>98%). Maximal loadings reached ∼30 wt% reflecting the strong interaction between the drug and the iron trimesate matrices. Neither degradation nor loss of crystalline structure was observed after the loading process. Storage of the loaded nanoMOFs in water did not result in drug release over three days. However, Gem-MP was released in media containing phosphates, as a consequence to particle degradation. Drug-loaded nanoMOFs were effective against pancreatic PANC-1 cells, in contrast to free drug and empty nanoMOFs. However, an efflux phenomenon could contribute to reduce the efficacy of the nanocarriers. Size optimization and surface modification of the nanoMOFs are expected to further improve these findings.

Hydrogen peroxide is produced by E. coli challenged haemocytes and regulates phagocytosis, in the medfly Ceratitis capitata. The active role of superoxide dismutase.

Hydrogen peroxide (H(2)O(2)) participates as a second messenger in cell signaling. In this paper, the role of H(2)O(2) was investigated, in Escherichia coli phagocytosis by the haemocytes of the medfly Ceratitis capitata. Block of H(2)O(2) synthesis by specific enzymic inhibitors, namely N-ethylmaleimide (NEM) for NADPH oxidase and diethyldithiocarbamate (DDC) for SOD, resulted in the increase of E. coli phagocytosis. Immunoblot analysis, flow cytometry and confocal microscopy, revealed the constitutive expression of SOD, in the medfly haemocytes. Phagocytosis increased by small interfering RNA (siRNA) for SOD, revealing the active involvement of SOD and H(2)O(2). Immunoblot analysis showed an increase of the ERK1/2 phosphorylation, in the presence of the above H(2)O(2) synthesis enzymic inhibitors. In addition, confocal microscopy showed no co-localization of SOD with ß integrin subunit. It appears that SOD participates in the regulation of bacterial phagocytosis, due to involvement of the produced H(2)O(2) in the differential phosphorylation of MAP kinases.

Regulators and signalling in insect haemocyte immunity.

The innate immune system of insects relies on both humoral and cellular immune responses that are mediated via activation of several signalling pathways. Haemocytes are the primary mediators of cell-mediated immunity in insects, including phagocytosis, nodulation, encapsulation and melanization. The last years, research has focused on the mechanisms of microbial recognition and activation of haemocyte intracellular signalling molecules in response to invaders. The powerful tool, RNA interference gene silencing, helped several regulators involved in immune responses, to be identified. In this review, we summarize recent advances in understanding the role(s) of receptors and intracellular signalling molecules involved in immune responses.

A beta integrin subunit regulates bacterial phagocytosis in medfly haemocytes.

We have recently reported that the activation of focal adhesion kinase (FAK) and its downstream targets upon pathogen challenge regulate phagocytosis in medfly haemocytes. The goal of this study was to further explore the signalling pathway underlying the process of phagocytosis. In particular, in this report, we used flow cytometry, RNA interference, enzyme-linked immunosorbent assay, Western blot and immunoprecipitation analysis to demonstrate the haemocyte surface receptor, through which the extracellular signals in response to bacteria are transmitted intracellularly. The presented data demonstrate the expression of a beta integrin subunit in the surface of medfly haemocytes that transmits signals upon pathogen triggering to FAK and its downstream targets, Src, MAP kinases and Elk-1-like protein, for the engulfment of pathogen. Interestingly LPS is not internalized through integrins.

A short and convenient chemical route to optically pure 2-methyl chromanmethanols. Total asymmetric synthesis of beta-, gamma-, and delta-tocotrienols.

With use of inexpensive commercially available raw materials, chromanmethanol precursors to the natural beta-, gamma-, and delta-tocotrienols have been prepared in high yield. Enzymatic resolution afforded chiral chromanmethanols in high enantiomeric excess. Subsequent attachment of the farnesyl side chain was high yielding, thus allowing the preparation of asymmetric beta-, gamma-, and delta-tocotrienols in one final step wherein simultaneous deprotection of the phenol and removal of the sulfone group occurs. This chemistry provides the first synthesis of natural-series beta-tocotrienol.

Apoptosis in medfly hemocytes is regulated during pupariation through FAK, Src, ERK, PI-3K p85a, and Akt survival signaling.

Focal adhesion kinase (FAK) and its downstream signaling targets are implicated in the process of apoptosis induced by external stimuli, in several mammalian systems. In this report, we demonstrate, that medfly (Ceratitis capitata) hemocytes do undergo apoptosis during larval development. In particular, we show using Western blot, ELISA and flow cytometry analysis, that FAK expression silencing in transfected by FAK double-stranded RNA (dsRNA) hemocytes, enhances twofold hemocyte apoptosis, by signaling through Src, MEK/ERK, and PI-3K/Akt signaling pathways. FAK expression silencing, in response to FAK dsRNA treatment, blocks partially the phosphorylation of its downstream targets. Pre-incubation of hemocytes, with specific inhibitors of FAK downstream signaling molecules, demonstrated that all these inhibitors reduced hemocyte viability and enhanced the magnitude of apoptosis about threefold. This data suggest that these pathways contribute to hemocyte survival and/or death during development. The expression and phosphorylation of FAK, Src, PI-3K p85a, Akt, and ERK signaling molecules appear to be dependent upon developmental stages. The expression and phosphorylation of the above signaling molecules, in annexin-positive and annexin-negative hemocytes is also distinct. The maximum expression and phosphorylation of FAK, Src, PI-3K p85a, Akt, and ERK appeared in annexin-positive hemocytes, in both early and late apoptotic hemocytes. The novel aspect of this report is based on the fact that hemocytes attempt to suppress apoptosis, by increasing the expression/phosphorylation of FAK and, hence its downstream targets signaling molecules Src, ERK, PI-3K p85a, and Akt. Evidently, the basic survival pathways among insects and mammals appear to remain unchanged, during evolution.

Distinct signalling pathways promote phagocytosis of bacteria, latex beads and lipopolysaccharide in medfly haemocytes.

In insects, phagocytosis is an important innate immune response against pathogens and parasites, and several signal transduction pathways regulate this process. The focal adhesion kinase (FAK)/Src and mitogen activated protein kinase (MAPK) pathways are of central importance because their activation upon pathogen challenge regulates phagocytosis via haemocyte secretion and activation of the prophenoloxidase (proPO) cascade. The goal of this study was to explore further the mechanisms underlying the process of phagocytosis. In particular, in this report, we used flow cytometry, RNA interference, enzyme-linked immunosorbent assay, Western blot and immunoprecipitation analysis to demonstrate that (1) phagocytosis of bacteria (both Gram-negative and Gram-positive) is dependent on RGD-binding receptors, FAK/Src and MAPKs, (2) latex bead phagocytosis is RGD-binding-receptor-independent and dependent on FAK/Src and MAPKs, (3) lipopolysaccharide internalization is RGD-binding-receptor-independent and FAK/Src-independent but MAPK-dependent and (4) in unchallenged haemocytes in suspension, FAK, Src and extracellular signal-regulated kinase (ERK) signalling molecules participating in phagocytosis show both a functional and a physical association. Overall, this study has furthered knowledge of FAK/Src and MAPK signalling pathways in insect haemocyte immunity and has demonstrated that distinct signalling pathways regulate the phagocytic activity of biotic and abiotic components in insect haemocytes. Evidently, the basic phagocytic signalling pathways among insects and mammals appear to have remained unchanged during evolution.