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Abstract Pseudomonas aeruginosa, a common pathogen in nosocomial infections, presents significant global health challenges due to its high prevalence and mortality rates. However, the origins and distribution of this bacterium remain unclear, partly due to the lack of effective gene typing methods. This situation necessitates the establishment of trustworthy and high-resolution protocol for differentiating closely related P. aeruginosa strains. In this context, the present study attempted to undertake a comparative genomic analysis of multiple P. aeruginosa strains available in the public database NCBI, with the goal of identifying potential genetic markers for measuring the genetic diversity. The preliminary comparative analysis of 816 P. aeruginosa strains revealed notable variations in two genes—specifically, the CDF family iron/cobalt efflux transporter AitP and the protease modulator HflC—across 44 strains. These variations were associated with single amino acid repeats (SHRs) that responsible for encoding histidine residue. Additionally, comparative gene map analysis revealed differential clustering patterns in the Rsx and TAXI genes among 16 strains. Interestingly, the gene structure pattern observed in TAXI groups displayed a strong correlation with the SHRs pattern in the CDF and HflC groups. In addition, the SHRs pattern of CDF and HflC were strongly correlated with MLST sequence type number. Overall, the study present a novel genetic markers based on SHRs and gene cluster patterns, offering a reliable method for genotyping of P. aeruginosa.

Background/Objectives: Aging and chronic stress are regarded as the most important risk factors of cognitive decline. Aged spontaneously hypertensive rats (SHRs) represent a suitable model of age-related vascular brain diseases. The aim of this study was to explore the effects of chronic isolation stress in aging SHRs on their cognitive functions and response to acute stress, as well as the influence of the chronic oral intake of N-Pep-Zn, the Zn derivative of N-PEP-12. Methods: Nine-month-old SHRs were subjected to social isolation for 3 months (SHRiso group), and one group received N-pep-Zn orally (SHRisoP, 1.5 mg/100 g BW). SHRs housed in groups served as the control (SHRsoc). The behavioral study included the following tests: sucrose preference, open field, elevated plus maze, three-chamber sociability and social novelty and spatial learning and memory in a Barnes maze. Levels of corticosterone, glucose and proinflammatory cytokines in blood plasma as well as salivary amylase activity were measured. Restraint (60 min) was used to test acute stress response. Results: Isolation negatively affected the SHRs learning and memory in the Barnes maze, while the treatment of isolated rats with N-Pep-Zn improved their long-term memory and working memory impairments, making the SHRisoP comparable to the SHRsoc group. Acute stress induced a decrease in the relative thymus weight in the SHRiso group (but not SHRsoc), whereas treatment with N-Pep-Zn prevented thymus involution. N-pep-Zn mitigated the increment in blood cortisol and glucose levels induced by acute stress. Conclusions: N-pep-Zn enhanced the adaptive capabilities towards chronic (isolation) and acute (immobilization) stress in aged SHRs and prevented cognitive disturbances induced by chronic isolation, probably affecting the hypothalamo–pituitary–adrenal, sympathetic, and immune systems. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa, a common pathogen in nosocomial infections, presents significant global health challenges due to its high prevalence and mortality rates. However, the origins and distribution of this bacterium remain unclear, partly due to the lack of effective gene typing methods. This situation necessitates the establishment of trustworthy and high-resolution protocol for differentiating closely related P. aeruginosa strains. In this context, the present study attempted to undertake a comparative genomic analysis of multiple P. aeruginosa strains available in the public database NCBI, with the goal of identifying potential genetic markers for measuring the genetic diversity. The preliminary comparative analysis of 816 P. aeruginosa strains revealed notable variations in two genes—specifically, the CDF family iron/cobalt efflux transporter AitP and the protease modulator HflC—across 44 strains. These variations were associated with single amino acid repeats (SHRs) that responsible for encoding histidine residue. Additionally, comparative gene map analysis revealed differential clustering patterns in the Rsx and TAXI genes among 16 strains. Interestingly, the gene structure pattern observed in TAXI groups displayed a strong correlation with the SHRs pattern in the CDF and HflC groups. In addition, the SHRs pattern of CDF and HflC were strongly correlated with MLST sequence type number. Overall, the study present a novel genetic markers based on SHRs and gene cluster patterns, offering a reliable method for genotyping of P. aeruginosa. [ABSTRACT FROM AUTHOR]

Background/Objectives: Aging and chronic stress are regarded as the most important risk factors of cognitive decline. Aged spontaneously hypertensive rats (SHRs) represent a suitable model of age-related vascular brain diseases. The aim of this study was to explore the effects of chronic isolation stress in aging SHRs on their cognitive functions and response to acute stress, as well as the influence of the chronic oral intake of N-Pep-Zn, the Zn derivative of N-PEP-12. Methods: Nine-month-old SHRs were subjected to social isolation for 3 months (SHRiso group), and one group received N-pep-Zn orally (SHRisoP, 1.5 mg/100 g BW). SHRs housed in groups served as the control (SHRsoc). The behavioral study included the following tests: sucrose preference, open field, elevated plus maze, three-chamber sociability and social novelty and spatial learning and memory in a Barnes maze. Levels of corticosterone, glucose and proinflammatory cytokines in blood plasma as well as salivary amylase activity were measured. Restraint (60 min) was used to test acute stress response. Results: Isolation negatively affected the SHRs learning and memory in the Barnes maze, while the treatment of isolated rats with N-Pep-Zn improved their long-term memory and working memory impairments, making the SHRisoP comparable to the SHRsoc group. Acute stress induced a decrease in the relative thymus weight in the SHRiso group (but not SHRsoc), whereas treatment with N-Pep-Zn prevented thymus involution. N-pep-Zn mitigated the increment in blood cortisol and glucose levels induced by acute stress. Conclusions: N-pep-Zn enhanced the adaptive capabilities towards chronic (isolation) and acute (immobilization) stress in aged SHRs and prevented cognitive disturbances induced by chronic isolation, probably affecting the hypothalamo–pituitary–adrenal, sympathetic, and immune systems.

Advances in Raman instrumentation have led to the implementation of a remote dispersive Raman spectrometer on the Perseverance rover on Mars, which is used for remote sensing. For remote applications, dispersive spectrometers suffer from a few setbacks such as relatively larger sizes, low light throughput, limited spectral ranges, relatively low resolutions for small devices, and high sensitivity to misalignment. A spatial heterodyne Raman spectrometer (SHRS), which is a fixed grating interferometer, helps overcome some of these problems. Most SHRS devices that have been described use two fixed diffraction gratings, but a variance of the SHRS called the one-grating SHRS (1g-SHRS) replaces one of the gratings with a mirror, which makes it more compact. In a recent paper we described monolithic two-gratings SHRS, and in this paper, we investigate a single-grating monolithic SHRS (1g-mSHRS), which combines the 1g-SHRS with a monolithic setup previously tested at the University of South Carolina. This setup integrates the beamsplitter, grating, and mirror into a single monolithic device. This reduces the number of adjustable components, allows for easier alignment, and reduces the footprint of the device (35 × 35 × 25 mm with a weight of 80 g). This instrument provides a high spectral resolution (∼9 cm−1) and large spectral range (7327 cm−1) while decreasing the sensitivity to alignment with a field of view of 5.61 mm at 3m. We discuss the characteristics of the 1g-mSHRS by measuring the time-resolved remote Raman spectra of a few inorganic salts, organics, and minerals at 3 m. The 1g-mSHRS makes a good candidate for planetary exploration because of its large spectral range, greater sensitivity, competitively higher spectral resolution, low alignment sensitivity, and high light throughput in a compact easily aligned system with no moving parts. Graphical Abstract This is a visual representation of the abstract. [ABSTRACT FROM AUTHOR]

In recent years, due to the significant increase in hypertension, peptides which are able to reduce blood pressure have gained special interest by scientific research and food industry. Several bioactive peptides with ascertained ACE-inhibitory activity have been found in Parmigiano Reggiano (PR) cheese and/or mixtures deriving from its digestion in vitro, and this may be predictive of its potential antihypertensive effect in vivo. This study investigated the long-term effect of feeding (PR) cheese on blood pressure (BP) of spontaneously hypertensive rats (SHRs). A total of 30 male SHRs, 13 weeks old, were subdivided into 6 groups balanced for body weight and BP, to receive daily dietary supplementation with: 0.1–0.2–0.4–0.6 g PR/rat, captopril, and water. Systolic and diastolic BP were recorded every two weeks, for 10 weeks. Blood samples were collected at the end of the trial. Dietary integration with PR led to a transitory reduction in rats’ pressure in the first 35 days of treatment and pressure decreased in a dose-dependent manner. In the second part of the study, the beneficial effect of PR antihypertensive peptides may have been masked and reduced by the increase in BP of rats linked to the rise in age of animals. No PR derived peptides were detected in rats’ serum. Highlights: Parmigiano Reggiano (PR) cheese led to a transitory reduction in rats’ pressure in the first 35 days of treatment. This effect was PR dose dependent. The highest amounts of PR tested did not increase both systolic and diastolic blood pressures of hypertensive rats.

In recent years, due to the significant increase in hypertension, peptides which are able to reduce blood pressure have gained special interest by scientific research and food industry. Several bioactive peptides with ascertained ACE-inhibitory activity have been found in Parmigiano Reggiano (PR) cheese and/or mixtures deriving from its digestion in vitro, and this may be predictive of its potential antihypertensive effect in vivo. This study investigated the long-term effect of feeding (PR) cheese on blood pressure (BP) of spontaneously hypertensive rats (SHRs). A total of 30 male SHRs, 13 weeks old, were subdivided into 6 groups balanced for body weight and BP, to receive daily dietary supplementation with: 0.1–0.2–0.4–0.6 g PR/rat, captopril, and water. Systolic and diastolic BP were recorded every two weeks, for 10 weeks. Blood samples were collected at the end of the trial. Dietary integration with PR led to a transitory reduction in rats' pressure in the first 35 days of treatment and pressure decreased in a dose-dependent manner. In the second part of the study, the beneficial effect of PR antihypertensive peptides may have been masked and reduced by the increase in BP of rats linked to the rise in age of animals. No PR derived peptides were detected in rats' serum. Highlights: Parmigiano Reggiano (PR) cheese led to a transitory reduction in rats' pressure in the first 35 days of treatment. This effect was PR dose dependent. The highest amounts of PR tested did not increase both systolic and diastolic blood pressures of hypertensive rats. [ABSTRACT FROM AUTHOR]

Background: The current study presents the novel angiotensin II receptor blocker fluorophenyl benzimidazole (FPD) as an antihypertensive agent in the SHR model of hypertension. We investigated the role of cGMP, voltage-dependent L-type calcium channels, and BKCa channels in the vasorelaxant mechanisms of FPD in the rat superior mesenteric artery.Methods: The antihypertensive effect of FPD was examined using an invasive technique measuring blood pressure in SHR animals. Using a myograph, tension measurement was completed in the superior mesenteric artery to elucidate the mechanisms of vasorelaxation involving AT1 receptors, the NO/cGMP pathway, L-type calcium channels, and BKCa channels. Ion flux (Ca2+, K+) studies were conducted in aortic smooth muscle cells. Putative targets proteins were determined by in silico docking studies. A safety evaluation of FPD was carried out using Swiss albino mice.Results: FPD significantly decreased blood pressure in SHR. It relaxed superior mesenteric arteries in a concentration-dependent manner and significantly inhibited angiotensin II-induced contraction. The relaxation response was also mediated by an increase in tissue cGMP levels, inhibition of L-type calcium channels, and the opening of BKCa channels. FPD further enhanced efflux of K+ and inhibited Bay K8644-stimulated Ca2+ influx in aortic smooth muscle cells and docked well in an in silico study with the targets. It was well tolerated in the toxicity study.Conclusion: The present study reports the antihypertensive activity of novel AT-1 receptor blocker FPD at 50 and 100 mg kg−1 with cGMP, L-type calcium channels, and BKCa channels as putative targets of vasorelaxation, and was found safe in oral toxicity.

A monolithic spatial heterodyne Raman spectrometer (mSHRS) is described, where the optical components of the spectrometer are bonded to make a small, stable, one-piece structure. This builds on previous work, where we described bench top spatial heterodyne Raman spectrometers (SHRS), developed for planetary spacecraft and rovers. The SHRS is based on a fixed grating spatial heterodyne spectrometer (SHS) that offers high spectral resolution and high light throughput in a small footprint. The resolution of the SHS is not dependent on a slit, and high resolution can be realized without using long focal length dispersing optics since it is not a dispersive device. Thus, the SHS can be used as a component in a compact Raman spectrometer with high spectral resolution and a large spectral range using a standard 1024 element charge-coupled device. Since the resolution of the SHRS is not dependent on a long optical path, it is amenable to the use of monolithic construction techniques to make a compact and robust device. In this paper, we describe the use of two different monolithic SHSs (mSHSs), with Littrow wavelengths of 531.6 nm and 541.05 nm, each about 3.5 × 3.5 × 2.5 cm in size and weighing about 80 g, in a Raman spectrometer that provides ∼3500 cm−1 spectral range with 4–5 cm−1 and 8–9 cm−1 resolution, for 600 grooves/mm and 150 grooves/mm grating-based mSHS devices, respectively. In this proof of concept paper, the stability, spectral resolution, spectral range, and signal-to-noise ratio of the mSHRS spectrometers are compared to our bench top SHRS that uses free-standing optics, and signal to noise comparisons are also made to a Kaiser Holospec f/ 1.8 Raman spectrometer. [ABSTRACT FROM AUTHOR]

A new hyperspectral Raman imaging technique is described using a spatial heterodyne Raman spectrometer (SHRS) and a microlens array (MLA). The new technique enables the simultaneous acquisition of Raman spectra over a wide spectral range at spatially isolated locations within two spatial dimensions (x, y) using a single exposure on a charge-coupled device (CCD) or other detector types such as a complementary metal-oxide semiconductor (CMOS) detector. In the SHRS system described here, a 4×4mm MLA with 1600, 100 mm diameter lenslets is used to image the sample, with each lenslet illuminating a different region of the SHRS diffraction gratings and forming independent fringe images on the CCD. The fringe images from each lenslet contain the fully encoded Raman spectrum of the region of the sample ''seen'' by the lenslet. Since the SHRS requires no moving parts, all fringe images can be measured simultaneously with a single detector exposure, and in principle using a single laser shot, in the case of a pulsed laser. In this proof of concept paper, hyperspectral Raman spectra of a wide variety of heterogeneous samples are used to characterize the technique in terms of spatial and spectral resolution tradeoffs. It is shown that the spatial resolution is a function of the diameter of the MLA lenslets, while the number of spatial elements that can be resolved is equal to the number of MLA lenslets that can be imaged onto the SHRS detector. The spectral resolution depends on the spatial resolution desired, and the number of grooves illuminated on both diffraction gratings by each lenslet, or combination of lenslets in cases where they are grouped. [ABSTRACT FROM AUTHOR]

Aim: The objective of the present study was to investigate the effect of treadmill training at lactate threshold intensity on maximum time to exhaustion (MTE) and heart rate (HR) as well as behavioral changes after kainate (KA)-induced status epilepticus (SE) of spontaneously hypertensive rats (SHRs).

BACKGROUND: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin‐I‐converting enzyme (ACE) inhibitory activity of the peptide Leu‐Ser‐Gly‐Tyr‐Gly‐Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS: This peptide from protein‐rich wastes showed excellent ACE inhibitory activity (IC50 = 2.577 μmol L−1) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver–Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C‐terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. CONCLUSION: LSGYGP, with an IC50 value of 2.577 μmol L−1, has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food‐derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Eriobotrya japonica (EJ) is a traditional Chinese plant with high medicinal value. EJ extracts are reported to exhibit antioxidant and anti‐inflammatory biological attributes. The current study aims to evaluate the prospective efficacy of E. japonica leave extract (EJLE) against Angiotensin‐II induced cardiac hypertrophy in H9c2 cardiomyoblast and in spontaneously hypertensive rats (SHRs). For the in vitro studies, Angiotensin‐II pretreated H9c2 cells were treated with EJLE and analyzed through Western blotting and rhodamine phalloidin staining for their cardio‐protective attributes. In the in vivo studies, 12‐week‐old SHRs were randomly divided into groups: SHRs supplemented with EJLE, control SHR group supplemented with PBS; in addition, a control group of Wistar–Kyoto rats (WKY) was also employed. All rats were supplemented twice a week for 8 week time interval. Finally, echocardiography, morphological, histology, and Western blot analysis were performed to assess their role against cardiac hypertrophy. Interestingly, we could observe that supplementation of EJLE could rescue Ang‐II induced cardiac hypertrophy as evident through Western blot, rhodamine phalloidin staining, and Hematoxylin‐Eosin staining. Notably, morphological and echocardiography data provided further supports for their ability to ameliorate cardiac characteristics. Cumulatively, the results clearly suggests that supplementation of EJLE promotes cardio‐protective effects through amelioration of cardiac hypertrophy in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Background Many pathological mechanisms are involved in the development of arterial hypertension; disturbance of the rheological properties of blood and microvascular rarefaction are among those mechanisms. Objective The effect of p- tyrosol (Tyr) on hemorheological parameters and microvascularization in the cerebral cortex of spontaneously hypertensive rats (SHRs) at the stage of blood pressure rising (5–11 weeks) was studied. Methods Blood viscosity (BV), plasma viscosity (PV), hematocrit, erythrocyte aggregation and deformability, the oxygen transport capacity index (OTCI), and the capillary network in the cerebral cortex after the course of treatment of Tyr (50 mg/kg daily i.g. for 6 weeks) were studied. Control normotensive Wistar-Kyoto (WKY) rats and control SHRs received an equivalent amount of 1% starch mucilage. Results In comparison with WKY rats, disturbances of rheological blood parameters and a decrease in OTCI were revealed in control SHRs at the 11 weeks of life. By the end of the experiment, brain microvascular rarefaction was observed in the control SHRs (the average density of the capillary bed was reduced due to a decrease in the number of capillaries with a diameter of 3–7 μm). In SHRs rats treated with Tyr, BV and PV, the indices of erythrocyte aggregation were lower, and OTCI was higher in comparison with control SHRs. The density of the capillary network and the number of capillaries of 3–7 μm in the cerebral cortex of SHRs rats receiving Tyr were significantly higher than the corresponding values in control SHRs. Conclusion When Tyr is administered to young SHRs during the development of hypertension, it limits the development of hyperviscosity syndrome, improves the oxygen transport capacity and eliminates microvascular rarefaction in the cerebral cortex. [ABSTRACT FROM AUTHOR]

A spatial heterodyne Raman spectrometer (SHRS) is a variant of a Michelson interferometer in which the mirrors of a Michelson are replaced with two stationary diffraction gratings. When light enters the SHRS, it is reflected off of diffraction gratings at frequency-dependent angles that produce crossed wavefronts in space that can be imaged using a plane array detector. The crossed wavefronts, which represent a superposition of interference fringes, are converted to a Raman spectrum upon applying a Fourier transform. In this work, a new approach to intensity calibration is discussed that originates from modeling the shot noise produced by the SHRS and converting the real noise to idealized white noise as predicted by theory. This procedure has two effects. First, the technique produces Raman spectra with white noise. Second, when the mean of the noise is normalized to one, the technique produces Raman spectra where the intensity axis is equivalent to signal-to-noise ratio. The data reduction technique is then applied to the measurement of materials of interest to the planetary science community, including minerals and inorganic salts, at a distance of 5 m from the collecting optic. [ABSTRACT FROM AUTHOR]

The response of normal tissues/organs to SHRS is more complex than to conventional radiotherapy. Tolerance doses TD5/5 and TD50/5, proposed by Rubin and Casarett, cannot be simply used for SHRS. Instead of LQED2, the BED is advised. The term risk dose (RD) corresponds better than TD to the risk of late morphological and functional disorders (OAR). BED doses show a rapid gradient with increasing distance of the OAR from the tumour GTV. Other risk factors include the dose-volume relationship, OAR organization (serial or parallel) and the ratio of the FSU to the target call. Vasculoendothelial cell damage initiates series of processes resulting in clinical and functional late effect. Using available data and studies, RDmin and RDmax for doses are listed as physical and BED doses for various OAR and dose- -volume constraints. The RD values and constraints are rough estimates, since the available SHRS data are sparse and fragmentary, which should be interpreted cautiously and need further clinical validation. [ABSTRACT FROM AUTHOR]

Raman spectroscopy is ideally suited for planetary exploration because of its ability to unambiguously identify minerals, organic compounds, and biomarkers. Traditionally, Raman spectra were acquired with grating-based dispersive spectrometers that require tens of micrometer-sized entrance slits and thus limited light throughput. Recently, we have evaluated a new type of Fourier transform Raman spectrometer, the spatial heterodyne Raman spectrometer that provides high spectral resolution in a compact system without limiting light throughput. In this work, we present time-resolved Raman spectra of carbonate, sulfate, and silicate minerals, including low Raman scattering efficiency olivine and feldspar minerals, in the 100-1260 cm−1 Raman fingerprint region with spatial heterodyne Raman spectrometer using 1.5-cm-diameter pulsed 532.078-nm Nd:YAG laser beam. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This work describes a method of applying the Fourier transform to the two-dimensional Fizeau fringe patterns generated by the spatial heterodyne Raman spectrometer (SHRS), a dispersive interferometer, to correct the effects of certain types of optical alignment errors. In the SHRS, certain types of optical misalignments result in wavelength-dependent and wavelength-independent rotations of the fringe pattern on the detector. We describe here a simple correction technique that can be used in post-processing, by applying the Fourier transform in a row-by-row manner. This allows the user to be more forgiving of fringe alignment and allows for a reduction in the mechanical complexity of the SHRS. [ABSTRACT FROM AUTHOR]

In earlier works, we demonstrated a high-resolution spatial heterodyne Raman spectrometer (SHRS) for deep-ultraviolet (UV) Raman measurements, and showed its ability to measure UV light-sensitive compounds using a large laser spot size. We recently modified the SHRS by replacing the cube beam splitter (BS) with a custom plate beam splitter with higher light transmission, an optimized reflectance/transmission ratio, higher surface flatness, and better refractive index homogeneity than the cube beam splitter. Ultraviolet Raman measurements were performed using a SHRS modified to use the plate beam splitter and a matching compensator plate and compared to the previously described cube beam splitter setup. Raman spectra obtained using the modified SHRS exhibit much higher signals and signal-to-noise (S/N) ratio and show fewer spectral artifacts. In this paper, we discuss the plate beam splitter SHRS design features, the advantages over previous designs, and discuss some general SHRS issues such as spectral bandwidth, S/N ratio characteristics, and optical efficiency. [ABSTRACT FROM AUTHOR]

A spatial heterodyne Raman spectrometer (SHRS) with millimeter-sized optics has been coupled with a standard cell phone camera as a detector for Raman measurements. The SHRS is a dispersive-based interferometer with no moving parts and the design is amenable to miniaturization while maintaining high resolution and large spectral range. In this paper, a SHRS with 2.5mm diffraction gratings has been developed with 17.5 cm-1 theoretical spectral resolution. The footprint of the SHRS is orders of magnitude smaller than the footprint of charge-coupled device (CCD) detectors typically employed in Raman spectrometers, thus smaller detectors are being explored to shrink the entire spectrometer package. This paper describes the performance of a SHRS with 2.5mm wide diffraction gratings and a cell phone camera detector, using only the cell phone's built-in optics to couple the output of the SHRS to the sensor. Raman spectra of a variety of samples measured with the cell phone are compared to measurements made using the same miniature SHRS with high-quality imaging optics and a high-quality, scientific-grade, thermoelectrically cooled CCD. [ABSTRACT FROM AUTHOR]

The link between cerebral small vessel disease (CSVD) and epilepsy has been poorly investigated. Some reports suggest that CSVD may predispose to temporal lobe epilepsy (TLE). Aim of this study was to evaluate whether spontaneously hypertensive rats (SHRs), an established model of systemic hypertension and CSVD, have a propensity to develop TLE more than generalized seizures. To this aim, amygdala kindling, as a model of TLE, and pentylenetetrazole (PTZ)-induced kindling, as a model of generalized seizures, have been used to ascertain whether SHRs are more prone to TLE as compared to Wistar Kyoto control rats. While young SHRs (without CSVD) do not differ from their age-matched controls in both models, old SHRs (with CSVD) develop stage 5 seizures in the amygdala kindling model (TLE) faster than age-matched control rats without CSVD. At odds, no differences between old SHRs and age-matched controls was observed in the development of PTZ kindling. Enalapril pre-treatment prevented the development of CSVD and normalized kindling development to control levels in SHRs. No difference was observed in the response to pharmacological treatment with carbamazepine or losartan. Overall, our study suggests that uncontrolled hypertension leading to CSVD might represent a risk factor for TLE. Further experimental studies are needed to unravel other risk factors that, along with CSVD, may predispose to TLE. [ABSTRACT FROM AUTHOR]

A spatial heterodyne Raman spectrometer (SHRS) was used to measure transmission Raman spectra of highly scattering compounds. Transmission Raman spectral intensities of ibuprofen were only 2.4 times lower in intensity than backscatter Raman spectra. The throughput was about eight times higher than an f/1.8 dispersive spectrometer, and the width of the area viewed was found to be seven to nine times higher, using 50.8mm and 250mm focal length collection lenses. However, the signal-to-noise (S/N) ratio was two times lower for the SHRS than the f/1.8 dispersive spectrometer, apparently due to high levels of stray light. [ABSTRACT FROM AUTHOR]

A variety of biologically active products have been isolated from Gracilariopsis lemaneiformis. In the present study, two novel angiotensin-converting enzyme (ACE) inhibitory peptides, FQIN [M(O)] CILR, and TGAPCR, were screened and identified from G. lemaneiformis protein hydrolysates by LC-MS/MS. The IC50 values of FQIN [M(O)] CILR and TGAPCR were 9.64 ± 0.36 μM and 23.94 ± 0.82 μM, respectively. In the stability study, both peptides showed stabilities of pH, temperature, simulated gastrointestinal digestion, and ACE hydrolysis. The Lineweaver–Burk plot showed that the two peptides were noncompetitive inhibitors of ACE. Molecular docking simulated the intermolecular interactions of two peptides and ACE, and the two peptides formed hydrogen bonds with the active pockets of ACE. However, FQIN [M(O)] CILR was more closely linked to the active pockets of ACE, thereby exerting better ACE inhibition. Spontaneously hypertensive rats (SHRs) were studied with an oral dose of 10 mg/kg body weight. Both peptides reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) in SHRs, of which FQIN [M(O)] CILR was able to reduce the systolic blood pressure by 34 mmHg (SBP) (p < 0.05). Therefore, FQIN [M(O)] CILR was an excellent ACE inhibitory peptide.

BACKGROUND Some food proteins hydrolysates are found to possess multiple health effects. In this study, walnut protein ( WP) was enzymatically hydrolysed by alcalase and trypsin under optimal conditions. The physico-chemical properties, antioxidant and angiotensin-converting enzyme ( ACE) inhibitory activities of WP, alcalase-generated walnut protein hydrolysate (AWPH) and trypsin-generated walnut protein hydrolysate (TWPH) were comparatively studied. Stability properties of the walnut protein hydrolysate (WPH) and the antihypertensive activity in spontaneously hypertensive rats ( SHRs) were also investigated. RESULTS The WPH showed higher physico-chemical properties, antioxidant activities, ACE inhibitory activity and stability against thermal treatment and gastrointestinal digestion than WP. The results of antihypertensive effects in SHRs showed that the most potent decrease of AWPH and TWPH in the systolic blood pressure occurred at 4 h (−26 mmHg) and 6 h (−30 mmHg) after administration. The study indicated that the WPH could significantly decrease the systolic blood pressure ( P < 0.05). CONCLUSION The WPH exhibited high physico-chemical properties, potent inhibitory activities and high stability. TWPH was more effective than AWPH in the detected properties. The results would be helpful for the comprehensive utilisation of the walnut resources. © 2015 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Angiotensin type 1a receptor (AT1aR) is thought to play an important role in the development of hypertension. However, it is unknown how the AT1aR expression in vascular tissue is changed during the development of hypertension or if the degree of methylation in the AT1aR promoter correlates with the expression of AT1aR. To address these questions, we measured AT1aR mRNA, protein expression, and methylation status of the AT1aR promoter in the aorta and mesenteric artery of male spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rats acting as controls at pre-hypertensive (4 weeks), evolving (10 weeks), and established (20 weeks) stages of hypertension. The expression of the AT1aR mRNA and protein was not different between the SHRs and WKY rats at 4 weeks. However, they were significantly greater in SHRs than in WKY rats at 20 weeks. Bisulfite sequencing revealed that the AT1aR promoter from the aorta and mesenteric artery of the SHRs was progressively hypo-methylated with age as compared with their WKY rat counterparts. These results suggest that the heightened AT1aR expression in SHRs is related to the AT1aR promoter hypo-methylation, which might be a consequence of the increased blood pressure and may be important in the maintenance of high blood pressure. [ABSTRACT FROM AUTHOR]

Highlights: [•] CST exerted antihypertensive and neuroprotective effects. [•] CST interacted with GABAergic systems and increased activities. [•] Akt and ERK signaling were involved in neuroprotective mechanisms. [•] CST+MUS may constitute new therapeutic agents for neurovascular disorders. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Rosa rugosa Thunb.''s flowers have been used for medicinal and food purposes for hundreds years in China. They have been used in Traditional Chinese Medicine (TCM) to effectively help in expansion of blood vessels and improvement of microcirculation. Current high prevalence of hypertension, and the associated side effects of synthetic Angiotensin I converting enzyme inhibitors usually prescribed for this condition, led us to the investigation of possible inhibitory activity of the Rosa rugosa Thunb. flower extracts on Angiotensin I converting enzyme (ACE). Materials and methods: Two different extraction preparation: (1) powdered materials were extracted with water (RW) and then with water (RWW), ethyl acetate (RWE) and 95% ethanol (RWE95); (2) powdered materials were extracted with 95% ethanol (RE95) and then with water (RE95W), ethyl acetate (RE95E) and 95% ethanol (RE95E95). The inhibition activity was determined using in vitro the inhibitory effect on Angiotensin I converting enzyme (ACE), and using the acute response and chronic response on blood pressure which measured in spontaneously hypertensive rats (SHRs). Results: Both RE95E95 and RWW had highest ACE inhibitor activities. The higher inhibitor activity of RE95E95 was also evaluated in SHRs by oral administration for antihypertensive effect. In acute experiment, the decrease in systolic blood pressure (SBP) and the increase in heart rate (HR) was observed at 2h after administration at high (40g/kg) and low (20g/kg) dose; such reductions in SBP were maintained for 12h. Low dose had reduced SBP significantly more than high dose. In multiple oral administration chronic experiment, a SBP reduction of 17.5mmHg was observed after 6d administration at low dose, and such reductions were maintained for the next 8 days. Conclusions: The experimental results demonstrated the antihypertensive effect of Rosa rugosa Thunb. flowers, which was attributed to inhibition of Angiotensin I converting enzyme. [Copyright &y& Elsevier]

Abstract: Two studies of variables affecting voluntary ethanol consumption by adolescent male and female rats are reported. Sprague–Dawley (SD) and spontaneously hypertensive rats (SHRs) were compared in Experiment 1. Starting on postnatal day 30 all had 24-h access to 2%, then 4%, and then 6% ethanol, followed by 1-h access to the 6% until intake stabilized. During the 1-h access SHR females consumed more ethanol than all other groups. In Experiment 2, the same procedure was used to compare SD groups prenatally exposed to nicotine, with controls. Nicotine-exposed females consumed more ethanol during 1-h access than both nicotine-exposed and control males; but after using water intake as a covariate, the differences were not significant. These data show that deprivation conditions need to be considered when generalizing the results of voluntary consumption studies, and that estrogens may be a modulator of addictive behavior. [Copyright &y& Elsevier]

Previous studies including ours demonstrated a hypotensive response to ethanol in spontaneously hypertensive rats (SHRs). In this study, we investigated whether this hypotensive effect of ethanol involves alterations in vascular α1-adrenergic receptor responsiveness. The contractile responses to the α1-receptor agonist phenylephrine were evaluated in aortic rings obtained from pair-fed SHRs receiving liquid diet with or without ethanol (2.5% or 5%, w/v) for 3 months. The responses were measured in aortas with and without endothelium to determine the role of the endothelium in the observed responses. The liquid diet intake was similar in the control and ethanol groups throughout the study whereas the body weight was significantly reduced by ethanol. Cumulative addition of phenylephrine (1 × 10−9–1 × 10−4 M) caused concentration-related contractile responses. These responses were significantly reduced after endothelium denudation suggesting a role for the endothelium in the modulation of α1-receptor responsiveness. Ethanol (2.5% and 5%) caused significant and concentration-related increases in the contractile responses elicited by phenylephrine but not KCl. The maximum contraction (Emax) caused by phenylephrine in rings obtained from SHRs treated with 2.5% and 5% ethanol amounted to 413.6 ± 26.3 and 513.0 ± 46.7 mg tension/mg tissue, respectively, compared with 383.6 ± 35.2 mg tension/mg tissue in control rings. The enhancement of α1 contractions by ethanol was virtually abolished in rings pretreated with the α1-receptor antagonist prazosin, suggesting upregulation of α1-receptors in aortas of ethanol-fed rats. Endothelium denudation also abolished ethanol-evoked increases in phenylephrine contractions. These findings suggest that chronic ethanol feeding upregulates aortic α1-receptors, which may be a consequence of chronic α1-receptor blockade by ethanol. The latter may account, at least in part, for the hypotensive response elicited by ethanol in SHRs. [ABSTRACT FROM AUTHOR]

Background: The current study presents the novel angiotensin II receptor blocker fluorophenyl benzimidazole (FPD) as an antihypertensive agent in the SHR model of hypertension. We investigated the role of cGMP, voltage-dependent L-type calcium channels, and BKCa channels in the vasorelaxant mechanisms of FPD in the rat superior mesenteric artery. Methods: The antihypertensive effect of FPD was examined using an invasive technique measuring blood pressure in SHR animals. Using a myograph, tension measurement was completed in the superior mesenteric artery to elucidate the mechanisms of vasorelaxation involving AT1 receptors, the NO/cGMP pathway, L-type calcium channels, and BKCa channels. Ion flux (Ca2+, K+) studies were conducted in aortic smooth muscle cells. Putative targets proteins were determined by in silico docking studies. A safety evaluation of FPD was carried out using Swiss albino mice. Results: FPD significantly decreased blood pressure in SHR. It relaxed superior mesenteric arteries in a concentration-dependent manner and significantly inhibited angiotensin II-induced contraction. The relaxation response was also mediated by an increase in tissue cGMP levels, inhibition of L-type calcium channels, and the opening of BKCa channels. FPD further enhanced efflux of K+ and inhibited Bay K8644-stimulated Ca2+ influx in aortic smooth muscle cells and docked well in an in silico study with the targets. It was well tolerated in the toxicity study. Conclusion: The present study reports the antihypertensive activity of novel AT-1 receptor blocker FPD at 50 and 100 mg kg−1 with cGMP, L-type calcium channels, and BKCa channels as putative targets of vasorelaxation, and was found safe in oral toxicity. [ABSTRACT FROM AUTHOR]

An untargeted multi-omics study implicated the potential dysregulation of fatty acid, nucleotide, and energy metabolism in the brainstems of spontaneously hypertensive rats (SHRs). A further quantitative exploration of the alterations in the metabolic pathways is necessary for a deep understanding of the central nervous system in SHRs. Targeted metabolic profiling of 40 fatty acids (PeptideAtlas: PASS01671) and 32 metabolites of nucleotides and energy metabolism (PeptideAtlas: PASS01672) and parallel reaction monitoring analysis of 5 proteins (PeptideAtlas: PASS01673) were performed on the brainstems of SHRs ( n = 8, 11 weeks old) and normotensive Wistar rats ( n = 8, age-matched) using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem MS. The targeted profiling results of metabolites and proteins revealed decreased polyunsaturated fatty acid (PUFA) synthesis with a significant downregulation of cis -11,14-eicosadienoic acid, cis -13,16-docosadienoic acid, and docosatetraenoate and impaired PUFA oxidation with the accumulation of γ-linolenate induced by the significantly downregulated expression of 2,4-dienoyl-CoA reductase ( p < 0.05). Dysregulated GTP and ATP metabolism was observed, with significantly decreased GDP and ADP ( p < 0.05) correlated with reduced GTPases of guanine nucleotide-binding protein subunit beta-1 (GNB1), transforming protein RhoA (RHOA), and Rho-related GTP-binding protein RhoB (RHOB) in the brainstem of SHRs. In addition, protein-arginine deiminase type-2 was significantly reduced in the brainstems of SHRs ( p < 0.05). The aberrant PUFA and energy metabolism might help to explain the alterations in the brainstem of SHRs. The findings on both metabolites and proteins could provide systemic insights into the pathology basis of altered PUFA and energy metabolism in hypertension, especially in the central nervous system.

In this study, we investigated the antihypertensive effects in vitro and in vivo of novel angiotensin-converting enzyme inhibitory (ACEI) peptides purified and identified from bovine bone gelatin hydrolysate (BGH). Thirteen ACEI peptides were identified from BGH, and among which, RGL-(Hyp)-GL and RGM-(Hyp)-GF exhibited high ACE inhibition with IC 50 values of 1.44 and 10.23 μM. Molecular docking predicted that RGM-(Hyp)-GF and ACE residues of Glu384, His513, and Lys511 formed hydrogen-bonding interactions at distances of 2.57, 2.99, and 2.42 + 3.0 Å. RGL-(Hyp)-GL formed hydrogen bonds with Lys511 and Tyr523 and generated hydrogen-bonding interactions with His387 and Glu411 in the zinc(II) complexation motif at distances of 2.74 and 3.03 + 1.93 Å. The maximal decrements in systolic blood pressure in spontaneously hypertensive rats induced by one-time gavage of RGL-(Hyp)-GL and RGM-(Hyp)-GF at 30 mg/kg were 31.3 and 38.6 mmHg. RGL-(Hyp)-GL had higher enzyme degradation resistance than that of RGM-(Hyp)-GF in vitro incubation in rat plasma, and they were sequentially degraded into pentapeptides and tetrapeptides within 2 h. Our results indicate that BGH can serve as a nutritional candidate to control blood pressure.

Myocardial apoptosis and fibrosis represent important contributing factors for development of hypertension-induced heart failure. The present study aims to investigate the potential effects of Eriobotrya japonica leaf extract (EJLE) against hypertension-induced cardiac apoptosis and fibrosis in spontaneously hypertensive rats (SHRs). Twelve-week-old male rats were randomly divided into four different groups; control Wistar Kyoto (WKY) rats, hypertensive SHR rats, SHR rats treated with a low dose (100 mg/kg body weight) of EJLE and SHR rats treated with a high dose (300 mg/kg body weight) of EJLE. Animals were acclimatized for 4 weeks and thereafter were gastric fed for 8 weeks with two doses of EJLE per week. The rats were then euthanized following cardiac functional analysis by echocardiography. The cardiac tissue sections were examined by Terminal Deoxynucleotidyl Transferase-Mediated Deoxyuridine Triphosphate (dUTP) Nick End-Labeling (TUNEL) assay, histological staining and Western blotting to assess the cardio-protective effects of EJ in SHR animals. Echocardiographic measurements provided convincing evidence to support the ability of EJ to ameliorate crucial cardiac functional characteristics. Furthermore, our results reveal that supplementation of EJLE effectively attenuated cardiac apoptosis and fibrosis and also enhanced cell survival in hypertensive SHR hearts. Thus, the present study concludes that EJLE potentially provides cardio-protective effects against hypertension-induced cardiac apoptosis and fibrosis in SHR animals. [ABSTRACT FROM AUTHOR]

Melatonin is involved in the control of circadian and seasonal rhythmicity, possesses potent antioxidant activity, and exerts a neuroprotective and anticonvulsant effect. Spontaneously hypertensive rats (SHRs) are widely accepted as an experimental model of essential hypertension with hyperactivity, deficient sustained attention, and alterations in circadian autonomic profiles. The purpose of the present study was to determine whether melatonin treatment during epileptogenesis can prevent the deleterious consequences of status epilepticus (SE) in SHRs in the kainate (KA) model of temporal lobe of epilepsy (TLE). Spontaneous recurrent seizures (SRSs) were EEG- and video-recorded during and after the treatment protocol. Melatonin (10mg/kg diluted in drinking water, 8weeks) increased the seizure-latent period, decreased the frequency of SRSs, and attenuated the circadian rhythm of seizure activity in SHRs. However, melatonin was unable to affect the disturbed diurnal rhythms and behavioral changes associated with epilepsy, including the decreased anxiety level, depression, and impaired spatial memory. Melatonin reduced neuronal damage specifically in the CA1 area of the hippocampus and piriform cortex and decreased hippocampal serotonin (5-HT) levels both in control and epileptic SHRs. Although long-term melatonin treatment after SE shows a potential to attenuate seizure activity and neuronal loss, it is unable to restore epilepsy-associated behavioral abnormalities in SHRs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Eucommia ulmoides Oliv. (Family Eucommiaceae), also known as Dù-zhòng (Chinese: ), Tuchong (in Japanese), is the sole species of the genus Eucommia. The leaf, stem, and bark as well as staminate flower of Eucommia ulmoides have been traditionally used to cure many diseases in China, Japan, Korea, among others. The aim of this review is to comprehensively outline the botanical description, ethnopharmacology, phytochemistry, biological activities, and toxicology of Eucommia ulmoides and to discuss possible trends for further study of Eucommia ulmoides., Materials and Methods: Information on Eucommia ulmoides was gathered via the internet (using Pub Med, Elsevier, Baidu Scholar, Google Scholar, Medline Plus, ACS, CNKI, and Web of Science) and from books in local libraries., Results: One-hundred twelve compounds of Eucommia ulmoides, including the main active constituents, lignans and iridoids, have been isolated and identified. In vitro and in vivo studies indicated that monomer compounds and extracts from Eucommia ulmoides possess wide-ranging pharmacological actions, especially in treating hypertension, hyperlipemia, diabetes, obesity, sexual dysfunction, osteoporosis, Alzheimer's disease, aging, lupus-like syndrome, and immunoregulation., Conclusions: Eucommia ulmoides has been used as a source of traditional medicine and as a beneficial health food. Phytochemical and pharmacological studies of Eucommia ulmoides have received much interest, and extracts and active compounds continue to be isolated and proven to exert various effects. Further toxicity and clinical studies are warranted to establish more detailed data on crude extracts and pure compounds, enabling more convenient preparations for patients. Therefore, this review on the ethnopharmacology, phytochemistry, biological activities, and toxicity of Eucommia ulmoides will provide helpful data for further studies as well as the commercial exploitation of this traditional medicine., (© 2013 Published by Elsevier Ireland Ltd.)

The aim of this study was to test the insulin-like growth factor-I (IGF-I) as a neuroprotective agent in a rat model for ischemic stroke and to compare its neuroprotective effects in conscious normotensive and spontaneously hypertensive rats. The effects of subcutaneous IGF-I injection were investigated in both rat strains using the endothelin-1 rat model for ischemic stroke. Motor-sensory functions were measured using the Neurological Deficit Score. Infarct size was assessed by Cresyl Violet staining. Subcutaneous administration of IGF-I resulted in significantly reduced infarct volumes and an increase in motor-sensory functions in normotensive rats. In these rats, IGF-I did not modulate blood flow in the striatum and had no effect on the activation of astrocytes as assessed by GFAP staining. In hypertensive rats, the protective effects of IGF-I were smaller and not always significant. Furthermore, IGF-I significantly reduced microglial activation in the cortex of hypertensive rats, but not in normotensive rats. More detailed studies are required to find out whether the reduction by IGF-I of microglial activation contributes to an impairment IGF-I treatment efficacy. Indeed, we have shown before that microglia in hypertensive rats have different properties compared to those in control rats, as they exhibit a reduced responsiveness to ischemic stroke and lipopolysaccharide., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Oxidative stress is implicated in the pathogenesis of both hypertension and epileptogenesis, therefore it could be used as a tool for studying co-morbidity of hypertension and epilepsy. Clinical data suggest that melatonin is a potent antioxidant that is effective in the adjunctive therapy of hypertension and neurodegenerative diseases. The present study aimed to explore and compare the efficacy of chronic pretreatment with melatonin infused via subcutaneous osmotic mini-pumps for 14 days (10 mg/kg per day) on kainic acid (KA)-induced status epilepticus, oxidative stress and expression of heat shock protein (HSP) 72 in spontaneously hypertensive rats (SHRs) and normotensive Wistar rats. SHRs showed higher lipid peroxidation (LP) in the frontal cortex and hippocampus and decreased cytosolic superoxide dismutase (SOD/CuZn) production in the frontal cortex compared to Wistar rats. Status epilepticus (SE) induced by KA (12 mg/kg, i.p.) was accompanied by increased LP and expression of HSP 72 in the hippocampus of the two strains and increased SOD/CuZn production in the frontal cortex of SHRs. Melatonin failed to suppress seizure incidence and intensity though the latency for seizure onset was significantly increased in SHRs. Melatonin attenuated the KA-induced increase in the level of LP in the hippocampus both in SHRs and Wistar rats. However, an increased activity in SOD/CuZn and mitochondrial SOD Mn as well as reduced expression of HSP 72 in the hippocampus was observed only in Wistar rats pretreated with melatonin. Taken together, the observed strain differences in the efficacy of chronic melatonin exposure before SE suggest a lack of a direct link between the seizure activity and the markers of oxidative stress and neurotoxicity., (© 2013.)