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Background Green feed diet in ruminants exerts a beneficial effect on rumen metabolism and enhances the content of milk nutraceutical quality. At present, a comprehensive analysis focused on the identification of genes, and therefore, biological processes modulated by the green feed in buffalo rumen has never been reported. We performed RNA-sequencing in the rumen of buffaloes fed a total mixed ration (TMR) + the inclusion of 30% of ryegrass green feed (treated) or TMR (control), and identified differentially expressed genes (DEGs) using EdgeR and NOISeq tools. Results We found 155 DEGs using EdgeR (p-values Gene Ontology analysis of DEGs identified using EdgeR revealed that green feed modulates biological processes relevant for the rumen physiology and, then, health and well-being of buffaloes, such as lipid metabolism, response to the oxidative stress, immune response, and muscle structure and function. Accordingly, we found: (i) up-regulation of HSD17B13, LOC102410803 (or PSAT1) and HYKK, and down-regulation of CDO1, SELENBP1 and PEMT, encoding factors involved in energy, lipid and amino acid metabolism; (ii) enhanced expression of SIM2 and TRIM14, whose products are implicated in the immune response and defense against infections, and reduced expression of LOC112585166 (or SAAL1), ROR2, SMOC2, and S100A11, encoding pro-inflammatory factors; (iii) up-regulation of NUDT18, DNAJA4 and HSF4, whose products counteract stressful conditions, and down-regulation of LOC102396388 (or UGT1A9) and LOC102413340 (or MRP4/ABCC4), encoding detoxifying factors; (iv) increased expression of KCNK10, CACNG4, and ATP2B4, encoding proteins modulating Ca2+ homeostasis, and reduced expression of the cytoskeleton-related MYH11 and DES. Conclusion Although statistically unpowered, this study suggests that green feed modulates the expression of genes involved in biological processes relevant for rumen functionality and physiology, and thus, for welfare and quality production in Italian Mediterranean dairy buffaloes. These findings, that need to be further confirmed through the validation of additional DEGs, allow to speculate a role of green feed in the production of nutraceutical molecules, whose levels might be enhanced also in milk.

delta-Valerobetaine (delta VB), a constitutive metabolite of ruminant milk, is produced in the rumen from free dietary N-epsilon- trimethyllysine occurring ubiquitously in vegetable kingdom. The biological role of delta VB is poorly known. Here, the anti-oxidant and anti-inflammatory potential of buffalo milk delta VB was tested in vitro during high-glucose (HG)-induced endothelial damage. Results indicated that delta VB (0.5 mM) ameliorated the HG cytotoxicity (0.57 +/- 0.02 vs 0.41 +/- 0.018 O.D. (P < 0.01). Interestingly, buffalo milk extracts enriched with delta VB showed improved significant efficacy in decreasing reactive oxygen species, lipid peroxidation, and cytokine release during HG treatment compared to milk extracts alone (P < 0.05). It is noteworthy that delta VB reduced the HG-activated inflammatory signal by modulating SIRT1 (0.96 +/- 0.05 vs 0.85 +/- 0.04 AU), SIRT6 (0.82 +/- 0.04 vs 0.61 +/- 0.03 AU), and NF-kappa B (0.85 +/- 0.03 vs 1.23 +/- 0.03 AU) (P < 0.05). On the whole, our data show the first evidence of delta VB efficacy in reducing endothelial oxidative stress and inflammation, suggesting a potential role of this betaine as a novel dietary compound with health-promoting properties.

SIGNIFICANCE: Oxidative stress represents the common hallmark of pathological conditions associated with cardiovascular disease (CVD), including atherosclerosis, heart failure, hypertension, aging, diabetes, and other vascular system-related diseases. The sirtuin (SIRT) family, comprising seven proteins (SIRT1-SIRT7) sharing a highly conserved nicotinamide adenine dinucleotide (NAD+)-binding catalytic domain, attracted a great attention for the past few years as stress adaptor and epigenetic enzymes involved in the cellular events controlling aging-related disorder, cancer, and CVD. Recent Advances: Among sirtuins, SIRT1 and SIRT6 are the best characterized for their protective roles against inflammation, vascular aging, heart disease, and atherosclerotic plaque development. This latest role has been only recently unveiled for SIRT6. Of interest, in recent years, complex signaling networks controlled by SIRT1 and SIRT6 common to stress resistance, vascular aging, and CVD have emerged. CRITICAL ISSUES: We provide a comprehensive overview of recent developments on the molecular signaling pathways controlled by SIRT1 and SIRT6, two post-translational modifiers proven to be valuable tools to dampen inflammation and oxidative stress at the cardiovascular level. FUTURE DIRECTIONS: A deeper understanding of the epigenetic mechanisms through which SIRT1 and SIRT6 act in the signalings responsible for onset and development CVD is a prime scientific endeavor of the upcoming years. Multiple "omic" technologies will have widespread implications in understanding such mechanisms, speeding up the achievement of selective and efficient pharmacological modulation of sirtuins for future applications in the prevention and treatment of CVD. Antioxid. Redox Signal. 28, 711-732.

We applied fission-track analysis on modern river sands to constrain the Cenozoic evolution of the Alps–Apennines junction zone. West of the Villalvernia-Varzi-Ottone fault, samples yielded major peaks at 33–36 and 62–65 Ma, showing that apatites in the eroded wedge-top successions were largely unreset. To the east, samples yielded prominent peaks at 4.0–4.7, 6.5–6.7 and 19 Ma, probably formed by reset ages. Our results indicate that the Alpine orogenic wedge originally tapered out to the south. The Northern Apennines were buried beneath a thick and widespread Epiligurian cover, now almost completely eroded, and experienced major uplift and erosional exhumation since early Pliocene times, at average rates of 1 km Ma−1. A large amount of Alpine-derived detritus, previously stored on top of the orogenic wedge, was transferred into the Po Plain. Sediment recycling thus overwhelmed any eventual effect of climate change on Plio-Quaternary sedimentation rates south of the Alps.

This review provides the current laboratory criteria for the detection and evaluation of the possible causes of alteration of non-concentrated industrial derivatives of tomatoes (peeled tomatoes, pulps, purees, sauces, and fillets), packaged in coated or uncoated tinplate cans. We discuss how the product alterations are typically the consequence of technological errors either in the can production, or in the storage process, or in the product sterilization. The described procedures include the quantitative determination of the distribution of gases (H

MiR-27b is highly expressed in endothelial cells (EC) but its function in this context is poorly characterized. This study aims to investigate the effect of miR-27b on inflammatory pathways, cell cycle, apoptosis, and mitochondrial oxidative imbalances in immortalized human aortic endothelial cells (teloHAEC), human umbilical vein endothelial cells (HUVEC), and human coronary artery endothelial cells (HCAEC) exposed to TNF-α. Treatment with TNF-α downregulates the expression of miR-27b in all EC lines, promotes the activation of inflammatory pathways, induces mitochondrial alteration and reactive oxygen species accumulation, fostering the induction of intrinsic apoptosis. Moreover, miR-27b mimic counteracts the TNF-α-related cytotoxicity and inflammation, as well as cell cycle arrest and caspase-3-dependent apoptosis, restoring mitochondria redox state, function, and membrane polarization. Mechanistically, hsa-miR-27b-3p targets the 3′untranslated regions of FOXO1 mRNA to downregulate its expression, blunting the activation of the Akt/FOXO1 pathway. Here, we show that miR-27b is involved in the regulation of a broad range of functionally intertwined phenomena in EC, suggesting its key role in mitigating mithochondrial oxidative stress and inflammation, most likely through targeting of FOXO1. Overall, results reveal for the first time that miR-27b could represent a possible target for future therapies aimed at improving endothelial health.

Ergothioneine (Egt) is a dietary amino acid which acts as an antioxidant to protect against ageing-related diseases. We investigated the anti-cancer properties of Egt in colorectal cancer cells (CRC). Egt treatment exerted cytotoxicity in a dose-dependent manner, induced reactive oxygen species accumulation, loss of mitochondrial membrane potential and upregulation of the histone deacetylase SIRT3. Immunoblotting analysis indicated that the cell death occurred via necroptosis through activation of the RIP1/RIP3/MLKL pathway. An immunoprecipitation assay unveiled that the interaction between the terminal effector in necroptotic signalling MLKL and SIRT3 increased during the Egt treatment. SIRT3 gene silencing blocked the upregulation of MLKL and abolished the ability of Egt to induce necroptosis. The SIRT3-MLKL interaction may mediate the necroptotic effects of Egt in CRC, suggesting the potential of this dietary amino thione in the prevention of CRC.

Recent pharmacological research on milk whey, a byproduct of the dairy industry, has identified several therapeutic properties that could be exploited in modern medicine. In the present study, we investigated the anticancer effects of whey from Mediterranean buffalo (Bubalus bubalis) milk. The antitumour effect of delactosed milk whey (DMW) was evaluated using the HCT116 xenograft mouse model of colorectal cancer (CRC). There were no discernible differences in tumour growth between treated and untreated groups. Nevertheless, haematoxylin and eosin staining of the xenograft tissues showed clearer signs of different cell death in DMW-treated mice compared to vehicle-treated mice. Detailed biochemical and molecular biological analyses revealed that DMW was able to downregulate the protein expression levels of c-myc, phospho-Histone H3 (ser 10) and p-ERK. Moreover, DMW also activated RIPK1, RIPK3, and MLKL axis in tumour tissues from xenograft mice, thus, suggesting a necroptotic effect. The necroptotic pathway was accompanied by activation of the apoptotic pathway as revealed by increased expression of both cleaved caspase-3 and PARP-1. At the molecular level, DMW-induced cell death was also associated with (i) upregulation of SIRT3, SIRT6, and PPAR-γ and (ii) downregulation of LDHA and PPAR-α. Overall, our results unveil the potential of whey as a source of biomolecules of food origin in the clinical setting of novel strategies for the treatment of CRC.

Emerging strategies to improve healthy aging include dietary interventions as a tool to promote health benefits and reduce the incidence of aging-related comorbidities. The health benefits of milk are also linked to its richness in betaines and short-chain acylcarnitines, which act synergistically in conferring anticancer, anti-inflammatory, and antioxidant properties. Whey, despite being a dairy by-product, still has a considerable content of bioactive betaines and acylcarnitines. Here, we investigated the anticancer properties of whey from Mediterranean water buffalo (Bubalus bubalis) milk by testing its antiproliferative effects in colorectal cancer (CRC) cells HT-29, HCT 116, LoVo and SW480. Results indicated that treatment with whey for 72 h inhibited cell proliferation (p &lt, 0.001), induced cell cycle arrest, and apoptosis via caspase-3 activation, and modulated cell metabolism by limiting glucose uptake and interfering with mitochondrial energy metabolism with the highest effects observed in HT-29 and HCT 116 cells. At molecular level, these effects were accompanied by upregulation of sirtuin 3 (SIRT3) (p &lt, 0.01) and peroxisome proliferator-activated receptor (PPAR)-γ expression (p &lt, 0.001), and downregulation of lactate dehydrogenase A (LDHA) (p &lt, 0.01), sterol regulatory-element binding protein 1 (SREBP1) (p &lt, 0.05), and PPAR-α (p &lt, 0.01). Transient SIRT3 gene silencing blocked the effects of whey on the LDHA, PPAR-γ, and PPAR-α protein expressions (p &lt, 0.01) suggesting that the whey capacity of perturbating the metabolic homeostasis in CRC cell lines is mediated by SIRT3.

In the present study, we aimed at assessing the influence of breed and feeding system on the bovine milk profile of betaines and carnitines and milk capacity in counteracting the inflammatory endothelial cell (EC) damage induced by interleukin (IL)-6. In the first experimental design, two breeds were chosen (Holstein vs. Modicana) to investigate the biomolecule content and antioxidant capacity in milk and dairy products. In the second experimental design, two feeding systems (pasture vs. total mixed ratio) were tested only in Holstein to evaluate the possible effect on the functional profile of milk and dairy products. Finally, the bulk milk from the two experimental designs was used to evaluate the efficacy of preventing IL-6-induced endothelial inflammatory damage. Results showed that Modicana milk and whey had higher biomolecule content and antioxidant activity compared to Holstein milk (p < 0.01). Milk from Holstein fed TMR showed higher concentration of γ-butyrobetaine, δ-valerobetaine (p < 0.01), and l-carnitine (p < 0.05). Similarly, whey from Holstein fed TMR also showed higher content of δ-valerobetaine, glycine betaine, l-carnitine, and acetyl-l-carnitine (p < 0.01) compared to the Holstein fed pasture. Conversely, the antioxidant activity of milk and dairy products was not affected by the feeding system. In ECs, all milk samples reduced the IL-6-induced cytokine release, as well as the accumulation of reactive oxygen species (ROS) and the induction of cell death, with the most robust effect elicited by Modicana milk (p < 0.01). Overall, Modicana milk showed a higher content of biomolecules and antioxidant activity compared to Holstein, suggesting that the breed, more than the feeding system, can positively affect the health-promoting profile of dairy cattle milk.

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p &lt, 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.

Dietary phenolic compounds possess potent bioactivity against inflammatory pathways of chronic inflammatory conditions, such as type 2 diabetes. Here, the phenolic profile and bioactivity of Italian red wines Gaglioppo, Magliocco, and Nerello Mascalese were characterized. NMR, HPLC/UV-Vis and spectrophotometric characterization showed that Magliocco was the richest wine in monomeric anthocyanins (two-fold), catechins, and low molecular weight phenolics (LMWP). A positive correlation was observed between the polyphenolic content and antioxidant capacity (p &lt, 0.05), with Magliocco displaying the highest antioxidant capacity (p &lt, 0.01). In vitro evidence on the endothelial cell models of insulin resistance and hyperglycemia showed the ability of Magliocco to reduce reactive oxygen species (ROS) (p &lt, 0.01) and cytokine release (p &lt, 0.01) and to upregulate SIRT1 and SIRT6 (p &lt, 0.01). On the whole, the results indicated that the quantitative and qualitative phenolic profiles of red wines influence their in vitro beneficial effects on oxidative and proinflammatory milieu in endothelial cells, showing a positive modulation of SIRT1 and SIRT6, both implied in vascular aging.

Recently, several concerns have been expressed on red meat quality and consumption. The aims of this study were to evaluate the influence of different breeding techniques and a prolonged post dry aging (PDA) maturation process on biomolecules level in raw buffalo meat. In the first experiment, two groups of animals were maintained with different space availability (15 vs. 10 m2/animal) for 90 days and biomolecules content was evaluated. In experiment 2, two diets (with or without ryegrass green forage) were used to assess the concentration of these biomolecules. Finally, in experiment 3, the meat of the animals that showed the highest content of biomolecules was chosen to assess the influence of the PDA maturation process. Buffaloes reared at 15 m2 showed a significantly (p &lt, 0.05) higher content of the considered biomolecules compared with their counterparts. Similarly, buffaloes fed green forage showed higher content of biomolecules (p &lt, 0.05) compared with the control group. The meat of the animals bred at 15 m2 and fed green forage showed a significant (p &lt, 0.01) increase of biomolecules content during the PDA maturation process up to 60 days without influence microbiological profile in terms of total aerobic bacterial counts, yeasts, and molds. In conclusion, breeding techniques and PDA maturation system could enhance biomolecules levels in terms of quality, without affect health standards.

Rationale Global warming has the potential to impact on the olfactory features of bergamot essential oil, which is a key component of perfumes, ointments and juices. Objectives The present study aimed at evaluating the hypothesis of a possible correlation between the chemical compositional characteristics of bergamot essential oil and climatic conditions over a twenty-year period (1999–2019) in Calabria. This Southern Italy region is responsible for ∼95 % of the worldwide production of bergamot oil. Materials and methods Unlike the vast majority of studies on stress tolerance that focus on a single stress condition, this study faced the challenge to evaluate the complex effects of a combination of different abiotic stress causes. It was found that the impoverishment of the olfactory qualities of bergamot essential oil reported for specific years closely correlate with the combination of heat waves and droughts. Chemically, the effect was attributed to dramatic compositional changes and to the massive accumulation of monoterpenes, in particular d -Limonene, in the fruit peel. Conclusions The data thus predict that, without a carefully planned increase of irrigation, the world bergamot industry may soon be jeopardized.

The effect of green feed on health-promoting biomolecules in milk was examined in dairy buffaloes. Buffaloes received a total mixed ration (TMR) (Control, C; n = 40) or TMR + alfalfa green feed (30% of diet) (Treated, T; n = 40). Biomolecules and functional activity were measured in milk obtained twice-monthly. Treated buffaloes had higher milk L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine and δ-valerobetaine (P < 0.01). They also had higher antioxidant activity (P < 0.01). Compared with C buffaloes, milk of T buffaloes improved the viability of endothelial cells exposed to high-glucose (P < 0.01), and reduced intracellular lipid peroxidation, reactive oxygen species (ROS), and cytokine release (P < 0.01). Milk of T buffaloes inhibited with greater potency the viability of human HCT116 and Cal 27 cancer cells (P < 0.001). The findings show that including green feed in the diet of dairy buffaloes enhances health-promoting biomolecules and the antioxidant and antineoplastic properties of milk.

International audience; Central Iran provides an ideal region in which to study the long-term morphotectonic response to the nucleation and propagation of intraplate faulting. In this study, a multidisciplinary approach that inte-grates structural and stratigraphic field investigations with apatite (U + Th)/He (AHe) thermochronometry is used to reconstruct the spatio-temporal evolution of the Kuh-e-Faghan Fault in northeastern central Iran. The Kuh-e-Faghan Fault is a narrow, similar to 80-km-long, deformation zone that consists of three main broadly left-stepping, E-W-trending, dextral fault strands that cut through the Mesozoic-Paleozoic substratum and the Neogene-Quaternary sedimentary cover. The AHe thermochronometry results indicate that the intrafault blocks along the Kuh-e-Faghan Fault experienced two major episodes of fault-related exhumation at ca. 18 Ma and ca. 4 Ma. The ca. 18 Ma faulting/exhumation episode is chiefly recorded by the structure and depositional architecture of the Neogene deposits along the Kuh-eFaghan Fault. A source-to-sink scenario can be reconstructed for this time frame, where topographic growth caused the synchronous erosion/exhumation of the pre-Neogene units and deposition of the eroded material in the surrounding fault-bounded continental depo-centers. Successively, the Kuh-eFaghan Fault gradually entered a period of relative tectonic quiescence and, probably, of regional subsidence, during which a thick pile of fine-grained onlapping sediments was deposited. This may have caused resetting of the He ages of apatite in the pre-Neogene and the basal Neogene successions. The ca. 4 Ma faulting episode caused the final exhumation of the fault system, resulting in the current fault zone and topography. The two faultrelated exhumation episodes fit with regional early Miocene collision-enhanced uplift/exhumation, and the late Miocene-early Pliocene widespread tectonic reorganization of the Iranian Plateau. The reconstructed longterm, spatially and temporally punctuated fault system evolution in intraplate central Iran during Neogene-Quaternary times may reflect states of far-field stress changes at the collisional boundaries.

Peripheral arterial disease (PAD) is a major health problem, especially when associated with severe hypertension. Administration of autologous bone marrow cells (BMCs) is emerging as a novel intervention to induce neoangiogenesis in ischemic limb models and in patients with PAD. This study evaluates the neovascularization capacity of BMCs alone or in combination with metabolic cotreatment (0.8% vitamin E, 0.05% vitamin C, and 5% of L-arginine) in a rat model of ischemic hindlimbs of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Molecular mechanisms were investigated in bone marrow-derived endothelial progenitor cells (BM-EPC) derived from rats. BMC therapy increased blood flow and capillary densities and Ki67 proliferative marker, and it decreased interstitial fibrosis. These effects were amplified by metabolic cotreatment, an intervention that induces vascular protection at least partly through the nitric oxide (NO)/endothelial nitric oxide synthase (eNOS) pathway, reduction of systemic oxidative stress, and macrophage activation. In addition, BMC therapy alone and, more consistently, in combination with metabolic treatment, ameliorated BM-EPC functional activity via decreased cellular senescence and improved homing capacity by increasing CXCR4-expression levels. These data suggest potential therapeutic effects of autologous BMCs and metabolic treatment in hypertensive PAD patients.

Since the first discovery of ultrahigh pressure (UHP) rocks 30 years ago in the Western Alps, the mechanisms for exhumation of (U)HP terranes worldwide are still debated. In the western Mediterranean, the presently accepted model of synconvergent exhumation (e.g., the channel-flow model) is in conflict with parts of the geologic record. We synthesize regional geologic data and present alternative exhumation mechanisms that consider the role of divergence within subduction zones. These mechanisms, i.e., (i) the motion of the upper plate away from the trench and (ii) the rollback of the lower plate, are discussed in detail with particular reference to the Cenozoic Adria-Europe plate boundary, and along three different transects (Western Alps, Calabria-Sardinia, and Corsica-Northern Apennines). In the Western Alps, (U)HP rocks were exhumed from the greatest depth at the rear of the accretionary wedge during motion of the upper plate away from the trench. Exhumation was extremely fast, and associated with very low geothermal gradients. In Calabria, HP rocks were exhumed from shallower depths and at lower rates during rollback of the Adriatic plate, with repeated exhumation pulses progressively younging toward the foreland. Both mechanisms were active to create boundary divergence along the Corsica-Northern Apennines transect, where European southeastward subduction was progressively replaced along strike by Adriatic northwestward subduction. The tectonic scenario depicted for the Western Alps trench during Eocene exhumation of (U)HP rocks correlates well with present-day eastern Papua New Guinea, which is presented as a modern analog of the Paleogene Adria-Europe plate boundary.

An extensive dataset of vitrinite reflectance, FTIR parameters on organic matter, illite content in mixed layers illite-smectite, apatite fission tracks and U-Th/He dating has been used to reconstruct the stepwise propagation of the Eastern Sicily fold-and-thrust belt during Late Palaeogene and Neogene times. The results indicate that the fold-and-thrust belt is divisible into two levels of thermal maturity. These levels consist of a less evolved level of thermal maturity that records limited sedimentary burial and minor heating, and a more evolved level of thermal maturity that indicates tectonic burial and exhumation at different times. Deformation and exhumation of shallowly buried units are linked to wedge forward propagation by low-angle thrusts, whereas the evolution of deeply buried units is associated with tectonic imbrications by duplex formation and steep thrusts. The two tectonic styles alternate during evolution of the fold-and-thrust belt under low erosion rates. © 2014 John Wiley & Sons Ltd.

The aim of this study was to compare the proteome profiles of the chorioamnion and corresponding caruncle for buffalo embryos that had either normal or retarded development on Day 25 after artificial insemination (AI). In experiment 1, embryos that were to subsequently undergo late embryonic mortality had a smaller width on Day 25 after AI than embryos associated with pregnancy on Day 45 after AI. In experiment 2, 25 Italian Mediterranean buffaloes underwent transrectal ultrasonography on Day 25 after AI, and pregnant animals were categorized as one of two groups based on embryonic width: normal embryos (embryonic width > 2.7 mm) and retarded embryos (embryonic width < 2.7 mm). Three buffaloes of each group were slaughtered on Day 27 after AI to collect chorioamnion and caruncle tissues for subsequent proteomic analyses. Two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight mass spectrometer analysis were used to ascertain the proteomic profiles. To confirm 2D-DIGE-results, three selected proteins were analyzed by Western blot. The proteomic profiles of the chorioamnion of retarded embryos and the corresponding caruncles showed differences in the expression of several proteins compared to normal embryos. In particular, a down-regulation was observed for proteins involved in protein folding (HSP 90-alpha, calreticulin), calcium binding (annexin A1, annexin A2), and coagulation (fibrinogen alpha-chain) (P < 0.05), whereas proteins involved in protease inhibition (alpha-1-antiproteinase, serpin H1, serpin A3-8), DNA and RNA binding (heterogeneous nuclear ribonucleoproteins A2/B1 and K), chromosome segregation (serine/threonine-protein phosphatase 2A), cytoskeletal organization (ezrin), cell redox homeostasis (amine oxidase-A), and hemoglobin binding (haptoglobin) were up-regulated (P < 0.05).

Coeval extensional and contractional tectonics are a common feature in orogenic belts, especially in post-collisional phases. The attempt to constrain their relative timing and the responsible mechanisms led to several models taking into account different geodynamic contexts of various mountain chains. In peri-Mediterranean collisional orogens, extension and compression are commonly associated and coeval to the emplacement of far-travelled/allochthonous units. Therefore their internal deformation acquired during the translation across collisional belts is likely imprinted by the extensional and contractional tectonics affecting the orogen.In the western portion of the Northern Apennines of Italy, one of the northernmost peri-Mediterranean Tertiary orogens, the far-travelled/allochthonous units, i.e., the Ligurian and Subligurian units, are widely exposed. The present study integrates published and newly acquired surface geological data (geological maps, cross-sections), subsurface boreholes data, and paleothermal (vitrinite reflectance, mixed layer illite-smectite and Kübler index) and thermochronological data (apatite fission-tracks) in order to investigate the deformation history and, consequently, the record of the extension-compression relationships within these far-travelled/allochthonous units.The study of modes and timing of reshaping of the far-travelled/allochthonous units allowed us to strengthen the hypothesis that extensional and contractional tectonics were coeval in the Northern Apennines and tightly connected by a cause/effect relationship. In particular, the late orogenic low- and high-angle extensional tectonics represent the response to an overall contractional regime which induced episodes of gravitational instability in the orogenic wedge. © 2013 Elsevier B.V.

We used vitrinite refl ectance and mixedlayered clay minerals to investigate levels of diagenesis of the Oligocene-Miocene basin developed on the nappes of the Alpine orogen exposed in the Peloritani Mountains (NE Sicily). Paleothermal indicators were integrated with stratigraphic and structural analyses and published apatite fi ssion-track and (U-Th-Sm)/He ages to defi ne the late evolutionary stages of the Peloritani Mountains. This multimethod approach allowed us to reconstruct the paleogeothermal gradient of the basin in Oligocene-Miocene times, to constrain its burial evolution, and discriminate between areas where it has been affected by sedimentary and/or tectonic load. In the southern area of the basin, organic and inorganic thermal parameters increase as function of depth, suggesting that their evolution was ruled by sedimentary burial. They record a decrease in paleogeothermal gradient values marking the evolution of the basin from a forearc to a thrust-top setting during the convergence-collision process between the Calabria-Peloritani Arc and the African plate. On the other hand, in the northern edge of the basin, vitrinite refl ectance values (0.46%‐0.58%) indicate that the thermal evolution of this area was controlled by tectonic burial related to late Langhian‐early Serravallian out-of-sequence thrust tec tonics. The tectonic overburden has been totally removed by extensional tectonics and/or erosion since the late Miocene. The short time span at maximum temperature (

BMC or HS alone, and BMC plus HS increased blood flow and capillary densities and decreased interstitial fibrosis. These effects were amplified by additional MT, at least in part, through the nitric oxide pathway, reduction of systemic oxidative stress and macrophage infiltration. Investigation of molecular mechanisms in bone marrow (BM)-derived progenitor cells from mice revealed that BMC therapy and Objective: Peripheral arterial disease (PAD) is a major health problem especially when associated to concomitant diabetes and hypercholesterolemia. Hyperglycemia with an overwhelming generation of oxygen radicals and formation of glycation end-products exacerbates oxidation-sensitive mechanisms activated by tissue ischemia. Administration of autologous bone marrow cells (BMC) is an increasing notable intervention to induce therapeutic angiogenesis, ameliorated by metabolic intervention (MT). Recently, hemangioblasts (HS) with functional properties were isolated. Methods: The effects of integrate regimen with intravenous BMC, HS, and MT (1.0% vitamin E, 0.05% vitamin C, and 6% l-arginine) were examined in the ischemic hindlimb of ApoE-/- diabetic and non-diabetic. Blood flow ratio was monitored by use of a laser Doppler blood flowmeter. Capillary density was determined in sections of the adductor and semimembranous muscles with antibody against CD31. Results: BMC or HS alone, and BMC plus HS increased blood flow and capillary densities and decreased interstitial fibrosis. These effects were amplified by additional MT, at least in part, through the nitric oxide pathway, reduction of systemic oxidative stress and macrophage infiltration. Investigation of molecular mechanisms in bone marrow (BM)-derived progenitor cells from mice revealed that BMC therapy and, more consistently, in combination with MT ameliorated functional activity via decreased cellular senescence and increased telomerase and chemokine CXCR4 activities. Telomerase activity was also increased by HS alone or HS. +. MT and, more consistently, by BMC. +. HS alone or in combination with MT. Conclusions/interpretation: Intravenous autologous BMC and HS intervention together with MT increased therapeutic angiogenesis in the ApoE-/- diabetic mouse hindlimb. © 2009 Elsevier Ireland Ltd.

Circulating endothelial progenitor cells (EPCs) play a significant role in regeneration of damaged blood vessels. Levels and functional activities of EPCs are noticeable altered by risk factors for coronary heart disease (CHD) and compounds that can prevent or ameliorate EPC dysfunction are currently of special clinical interest. Here, we evaluate the effects of red wine (RW) on EPCs in C57BL/6J mice subjected to physical exercise. FACS computed counting showed a significant increase of EPC number (P

Alteration of levels and functional activities of circulating endothelial progenitor cells (EPCs) induced by risk factors for coronary heart disease (CHD) profoundly influence their role in the regeneration of tissue ischemia and angiogenesis. Among antioxidant nutrients in the prevention of CHD, L-arginine is particularly effective in enhancing the protection afforded by moderate physical exercise. Here, we aimed to evaluate the effects of L-arginine on EPC levels in C57BL/6J mice subjected to moderate physical exercise. Results showed that supplementation with L-arginine potentiates the effects of moderate physical exercise by increasing significantly EPCs (P

Moderate wine intake is associated with a reduced risk of morbidity and mortality from cardiovascular disease. Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases also the endothelial expression of oxidation-sensitive responsive genes (such as ELK-1 and p-JUN). This study evaluates the effects of chronic consumption of red wine on perturbed shear stress-induced atherogenesis. Results indicated that chronic treatment with red wine significantly attenuated the activation of redox-sensitive genes (ELK-1 and p-JUN) and increased endothelial nitric oxide synthase (eNOS) expression (which was decreased by perturbed shear stress) in cultured human coronary endothelial cells (EC) and in atherosclerosis-prone areas of hypercholesterolemic mice. Oral administration of red wine to hypercholesterolemic mice reduced significantly the progression of atherosclerosis. Moreover, short-term supplementation with red wine to C57BL/6J mice significantly increased upregulation of aortic eNOS and SIRT1 expression induced by physical training. These findings establish that administration of low doses of red wine can attenuate the proatherogenic effects induced by perturbed shear stress in vitro and in vivo. This evidence may have implications for the prevention of atherosclerotic lesion progression and its clinical manifestations.

Metabolic syndrome includes most widely distributed clinical conditions such as obesity, hypertension, dislipidemia, and diabetes. Pomegranate fruit extract (PFE), rich in polyphenolic antioxidants, reduces the expression of oxidation-sensitive genes at the sites of perturbed shear-stress. The aim of this study was to evaluate the effect of PFE in comparison to regular pomegranate juice (PJ) and seed oil on the biological actions of nitric oxide (NO) and the arterial function in obese Zucker rats, a model of metabolic syndrome. Our results indicated that supplementation with PFE or PJ significantly decreased the expression of vascular inflammation markers, thrombospondin (TSP), and cytokine TGFbeta1 (P