Detection of microplastics based on splicing grating spatial heterodyne Raman spectroscopy.

As a new type of persistent pollutant, microplastics pose a serious threat to the earth's ecological environment and human health. Efficient and reliable microplastic detection technology is of great significance in the management of microplastic pollution. Aiming at the problems of low signal-to-noise ratio (SNR), narrow spectral range and low spectral resolution in traditional microplastic detection technology, a splicing grating spatial heterodyne Raman spectroscopy (SG-SHRS) is proposed in this paper. The splicing grating is composed of four sub-gratings with groove densities of 320, 298, 276 and 254 gr / mm, respectively. Each sub-grating has an independent sub-filter to improve the SNR of the system. The system is simulated, built and calibrated. The actual resolution of the SG-SHRS system is 0.7 cm-1, and the spectral detection range of a single sub-grating is 2947.2 cm-1. Four kinds of microplastics, polyamide (PA), polystyrene (PS), polycarbonate (PC), and polyphenylene sulfide (PPS), were detected by the SG-SHRS system. The complete Raman spectral information of microplastics was obtained, and the peak assignment of Raman characteristic peaks of the four kinds of microplastics was analyzed. By comparing the test results with a commercial dispersion spectrometer, it has been proven that the SG-SHRS system has the advantages of high spectral resolution, wide spectral range, and high SNR, and has good application prospects in the field of microplastic detection.

Ameliorative effect of mussel-derived ACE inhibitory peptides on spontaneous hypertension rats.

PURPOSE: The purpose of this study was to prepare the novel mussel-derived ACE inhibitory peptides (MEPs) by enzymatic hydrolysis of Mytilus edulis and investigate their antihypertensive effects in vivo. METHODS: After assessing the stability of MEPs in vitro, we investigated the effect of MEPs on hypertension using spontaneously hypertensive rats (SHRs). Subsequently, MEPs were purified and identified by ultrafiltration, gel filtration chromatography and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Our study demonstrated that MEPs could keep stable ACE inhibitory activity after treatment with heat, acid, alkali, metal ions and simulated gastrointestinal digestive fluid. Additionally, the animal experiments showed that both short-term and long-term treatment with MEPs resulted in a significant reduction in systolic and diastolic blood pressure in SHRs. Mechanistically, the results suggested that MEPs could reduce vascular remodeling, regulate renin-angiotensin system (RAS), and inhibit kidney and myocardial fibrosis. Finally, we isolated and identified five peptides from MEPs, with the peptide Ile-Leu-Thr-Glu-Arg showed the highest ACE inhibition rate. CONCLUSION: Our findings demonstrate the potential use of MEPs as active components in functional foods designed to lower blood pressure.

Spontaneously hypertensive rats vs. Wistar Kyoto and Wistar rats: An assessment of anxiety, motor activity, memory performance, and seizure susceptibility.

Spontaneously hypertensive rats (SHRs) are widely accepted for modeling essential hypertension and Attention deficit hyperactivity disorder (ADHD). However, data concerning central nervous system changes associated with behavioral responses of this strain and usage of Wistar Kyoto (WKY) rats as controls are confounding. The objective of the present study was to assess the impact of anxiety and motor activity on the cognitive responses of SHRs compared to Wistar and WKY rats. In addition, the role of brain-derived neurotrophic factor (BDNF) in the hippocampus on cognitive behavior and seizure susceptibility in the three strains was evaluated. In Experiment#1, SHR demonstrated impulsive responses in the novelty suppression feeding test accompanied by impaired spatial working and associative memory in the Y maze and object recognition test compared with the Wistar rat but not WKY rats. In addition, the WKY rats exhibited diminished activity compared to Wistar rats in an actimeter. In Experiment#2, the seizure susceptibility was assessed by 3-min electroencephalographic (EEG) recording after two consecutive injections of pentylenetetrazol (PTZ) (20+40 mg/kg). The WKY rats were more vulnerable to rhythmic metrazol activity (RMA) than the Wistar rats. In contrast, Wistar rats were more prone to generalized tonic-clonic seizures (GTCS) than WKY rats and SHRs. Control SHR had lower BDNF expression in the hippocampus compared to Wistar rats. However, while the BDNF levels were elevated in the Wistar and WKY rats after PTZ injection, no change in this signaling molecule was observed in the SHR in the seizure condition. The results suggest Wistar rats as a more appropriate control of SHR than WKY rats for studying memory responses mediated by BDNF in the hippocampus. The higher vulnerability to seizures in Wistar and WKY rats compared to SHR might be linked to PTZ-induced decreased expression of BDNF in the hippocampus.

Remote Raman Sensing Using a Single-Grating Monolithic Spatial Heterodyne Raman Spectrometer: A Potential Tool for Planetary Exploration.

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.

Stimulation of angiotensin II receptor 2 preserves cognitive function and is associated with an enhanced cerebral vascular density after stroke.

Angiotensin signaling is known to be sexually dimorphic. Although it is a well-studied target for intervention in stroke and cognitive impairment, female studies are rare. With females suffering a disproportionately greater negative impact of stroke and dementia vs. males, effective interventions are of utmost urgency. The aim of the current study was to determine the impact of activation of the angiotensin II type 2 receptor (AT2R) with the agonist compound 21 (C21) on the development of post-stroke cognitive impairment, after experimental ischemic stroke. Ovariectomized (OVX) spontaneously hypertensive rats (SHRs) were subjected to 1 h of middle cerebral artery occlusion (MCAO). At 24 h, rats with a significant neurologic deficit were randomized to receive either saline or C21 (0.03 mg/kg/day) intraperitoneally (IP) for 5 days, then orally (0.12 mg/kg/day) for a total of 6 weeks. Cognitive function, brain structure by MRI and vascular architecture by microCT angiography were measured. C21 preserved cognitive function, specifically spatial memory, and improved vascular density in the ischemic hemisphere at 6 weeks, reflecting both arteriogenesis and angiogenesis. In conclusion, C21 prevented cognitive impairment after stroke, likely through a mechanism involving vascular protection and restoration.

Telmisartan Attenuates the Growth of Epithelium-like Cells and Glomerular Injury in Spontaneously Hypertensive Rats.

The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats (SHRs) with hypertensive nephropathy. However, the characteristics of abnormal epithelium-like cells and their pathogenesis in hypertensive nephropathy are not fully understood. In the present study, we investigated the correlation of epithelium-like cells with glomerular injury, and the effects of early drug intervention with telmisartan, an anti-hypertensive drug, on the growth of epithelium-like cells. The results showed that the epithelium-like cells were obviously observed lining along the luminal surface of Bowman's capsule in glomeruli, significantly resulting in the atrophy of the glomerular tuft. Some of the epithelium-like cells strongly expressed proliferating cell nuclear antigen (PCNA) and vimentin, indicating active cellular proliferation. The incidence of epithelium-like cells varied from 13.6% to 54.4% of glomeruli in 48-week-old SHRs, and from 5.1% to 18.0% of glomeruli in age-matched Wistar-Kyoto (WKY) rats (P<0.01). The linear regression analysis further confirmed an obvious correlation between the incidence of epithelium-like cells and the glomerular injury. Moreover, early intervention with telmisartan could dramatically attenuate the progression of epithelium-like cells growth. However, no significant effect of telmisartan on the established epithelium-like cells was observed. Taken together, we demonstrated the involvement of abnormal epithelium-like cells growth in glomerular injury during hypertensive nephropathy in SHRs, and firstly showed the positive effects of the anti-hypertensive drug on the progression of epithelium-like cells growth.

A nationwide population-based prospective study of cirrhosis in Iceland.

BACKGROUND & AIMS: The incidence of cirrhosis in Iceland has been the lowest in the world with only 3 cases per 100,000 inhabitants. Alcohol consumption has almost doubled in Iceland from 1980 to 2016. Obesity has also risen and hepatitis C virus has spread among people who inject drugs in Iceland. The aim of this study was to evaluate the effects of these risk factors on the incidence and aetiology of cirrhosis in Iceland. METHODS: The study included all patients diagnosed with cirrhosis for the first time during 2010-2015. Diagnosis was based on liver histology or 2 of 4 criteria: cirrhosis on imaging, ascites, varices, and/or elevated INR. RESULTS: Overall, 157 patients were diagnosed, 105 (67%) males, mean age 61 years. The overall incidence was 9.7 cases per 100,000 inhabitants annually. Alcohol was the only underlying cause in 48/157 (31%), non-alcoholic fatty liver disease (NAFLD) in 34/157(22%), and alcohol and hepatitis C together in 23/157(15%) were the most common causes. Only 6% of patients had an unknown cause of cirrhosis. Upon diagnosis, the median model for end-stage liver disease score was 11 (IQR 8-15), 53% were of Child-Pugh class A whereas 61 (39%) had ascites, 11% encephalopathy, and 8% variceal bleeding. In all, 25% of deaths were from HCC and 25% from liver failure. CONCLUSION: A major increase in incidence of cirrhosis has occurred in Iceland associated with increases in alcohol consumption, obesity, and hepatitis C. In a high proportion NAFLD was the aetiology and very few had unknown cause of cirrhosis. The highest death rate was from HCC. LAY SUMMARY: In a nationwide population-based study from Iceland, including all patients diagnosed with cirrhosis of the liver over a period of 5 years, we found the incidence of new cases had increased 3-fold compared with a previous study 20 years ago. The increase is attributable to increased alcohol consumption, an epidemic of diabetes and obesity, and infection with the hepatitis C virus. Furthermore, we found that with thorough investigations, a specific cause for cirrhosis could be found in 94% of patients. Patients with cirrhosis frequently die of liver cancer and other complications related to their liver disease.

Targeted Metabolic Profiling and PRM Analysis of Proteins Revealed Impaired Polyunsaturated Fatty Acid Metabolism and GTP Metabolism in the Brainstem of Spontaneously Hypertensive Rats.

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.

Hypotensive and Hepatoprotective Properties of the Polysaccharide-Stabilized Foaming Composition Containing Hydrolysate of Whey Proteins.

Whey protein hydrolysates (WPHs) are one of the most promising sources of biofunctional peptides with such beneficial properties as antioxidant, antihypertensive, anti-inflammatory and others. WPHs also could be used as foaming agents for aerated products (e.g., milk shake type drinks). However, WPH alone has a bitter taste and foamed WPH should be stabilized by additional ingredients. Here, we present a composition including WPH and three polysaccharides-pumpkin pectin, sodium alginate and ι-carrageenan-used as foam stabilizers. Polysaccharide content was selected according to foaming, organoleptic antioxidant and angiotensin-I-converting enzyme inhibitory characteristics of the resulted composition. Further, the hypotensive, antioxidant and hepatoprotective properties of the composition were proved by in vivo tests performed in spontaneously hypertensive rats and Wistar rats with CCl4-induced hepatic injury.

Antihypertensive Effect of a Novel Angiotensin II Receptor Blocker Fluorophenyl Benzimidazole: Contribution of cGMP, Voltage-dependent Calcium Channels, and BKCa Channels to Vasorelaxant Mechanisms.

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.

Steroid Hormone Receptors: Links With Cell Cycle Machinery and Breast Cancer Progression.

Progression of cells through cell cycle consists of a series of events orchestrated in a regulated fashion. Such processes are influenced by cell cycle regulated expression of various proteins where multiple families of transcription factors take integral parts. Among these, the steroid hormone receptors (SHRs) represent a connection between the external hormone milieu and genes that control cellular proliferation. Therefore, understanding the molecular connection between the transcriptional role of steroid hormone receptors and cell cycle deserves importance in dissecting cellular proliferation in normal as well as malignant conditions. Deregulation of cell cycle promotes malignancies of various origins, including breast cancer. Indeed, SHR members play crucial role in breast cancer progression as well as management. This review focuses on SHR-driven cell cycle regulation and moving forward, attempts to discuss the role of SHR-driven crosstalk between cell cycle anomalies and breast cancer.

Effects of Aqueous Extract of Lycopersicum esculentum L. var. "Camone" Tomato on Blood Pressure, Behavior and Brain Susceptibility to Oxidative Stress in Spontaneously Hypertensive Rats.

Behavioral disorders affect millions of people worldwide. Hypertension contributes to both the development and progression of brain damage and cognitive dysfunction and could represent the most powerful modifiable risk factor for cerebral vessel dysfunction and consequent behavioral impairment. Tomato contains antioxidants and bioactive molecules that might play an important role in the prevention of cardiovascular and brain diseases. The effects of the combined gel and serum from Lycopersicum esculentum L. var. "Camone" tomatoes and those of purified tomato glycoalkaloids (tomatine) and an antihypertensive drug (captopril) were investigated in male spontaneously hypertensive rats (SHRs) and compared with normotensive Wistar Kyoto (WKY) rats. Body weight, systolic blood pressure, behavioral parameters, as well as brain susceptibility to oxidative stress and brain cytokine contents, were assessed. Treating hypertensive rats with tomato gel/serum or captopril for four weeks caused a significant reduction in blood pressure, decreased locomotor activity and increased grooming behavior; the last two parameters were also significantly affected by tomatine treatment. Brain slices obtained from hypertensive rats treated with tomato gel/serum were more resistant to oxidative stress and contained lower levels of inflammatory cytokines than vehicle-treated ones. In contrast, tomatine treatment had no effect. In conclusion, the tomato-derived gel/serum can be considered a dietary supplement able to drive in vivo blood pressure towards healthier values and also control some central effects such as behavior and brain oxidative stress.

A Monolithic Spatial Heterodyne Raman Spectrometer: Initial Tests.

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.

Quantitative Evaluation of the Transcriptional Activity of Steroid Hormone Receptor Mutants and Variants Using a Single Vector With Two Reporters and a Receptor Expression Cassette.

Although the rapid development of high-throughput sequencing has led to the identification of a large number of truncated or mutated steroid hormone receptor (SHR) variants, their clinical relevance remains to be defined. A platform for functional analysis of these SHR variants in cells would be instrumental for better assessing their impact on normal physiology and SHR-associated diseases. Here we have developed a new reporter system that allows rapid and accurate assessment of the transcriptional activity of SHR variants in cells. The reporter is a single construct containing a firefly luciferase reporter gene, whose expression is under the control of a promoter with multiple steroid hormone responsive elements, and a Renilla luciferase reporter gene, that is constitutively expressed under the control of an internal ribosome entry site (IRES) and is not regulated by steroid hormones. The corresponding SHR (wildtype or mutant/variant) is also expressed from the same construct. Using this improved reporter system, we revealed a large spectrum of transactivation activities within a set of previously identified mutations and variations of the androgen receptor (AR), the estrogen receptor α (ERα) and the glucocorticoid receptor (GR). This novel reporter system enables functional analysis of SHR mutants and variants in physiological and pathological settings, offering valuable preclinical, or diagnostic information for the understanding and treatment of associated diseases.

Hyperspectral Raman Imaging Using a Spatial Heterodyne Raman Spectrometer with a Microlens Array.

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 × 4 mm MLA with 1600, 100 µm 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.

Antihypertensive Effects in Vitro and in Vivo of Novel Angiotensin-Converting Enzyme Inhibitory Peptides from Bovine Bone Gelatin Hydrolysate.

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 IC50 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.

Comparison of an angiotensin-I-converting enzyme inhibitory peptide from tilapia (Oreochromis niloticus) with captopril: inhibition kinetics, in vivo effect, simulated gastrointestinal digestion and a molecular docking study.

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.

Antihypertensive Effects of Two Novel Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptides from Gracilariopsis lemaneiformis (Rhodophyta) in Spontaneously Hypertensive Rats (SHRs).

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.

Eriobotrya japonica ameliorates cardiac hypertrophy in H9c2 cardiomyoblast and in spontaneously hypertensive rats.

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.

Anti-Apoptosis and Anti-Fibrosis Effects of Eriobotrya Japonica in Spontaneously Hypertensive Rat Hearts.

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.