Background and objective While hypertension (HTN) is a major health-related threat globally, it is often an under-reported clinical condition as most of the stage I hypertensive patients do not present with any symptoms. The relationship between endogenous oxygen-sensing protein [erythropoietin (EPO) and vascular endothelial growth factor (VEGF)] levels and vascular stress in hypertensive patients is not fully understood as the mechanistic pathway by which these oxygen-sensing proteins alter the vascular physiology and cause hypertension is still a matter of debate. In light of this, we explored the role of these two proteins in the development of vascular stress including increased pulse wave velocity (PWV). We aimed to examine the correlation between oxygen-sensing proteins and vascular stress markers including PWV in hypertensive patients. Materials and methods We conducted a cross-sectional study involving age-matched participants classified into three groups (group 1: normotensive persons, n=36; group 2: stage I hypertensive patients, n=36; and group 3, stage II hypertensive patients, n=36). Adiposity-related parameters such as waist circumference (WC), hip circumference (HC), BMI, and waist-hip ratio (WHR) were measured. BP was recorded manually in resting posture by using a sphygmomanometer. PWV, which predicts the progression of BP and the development of HTN, was recorded using a periscope, which works based on the oscillometric method. Vascular stress-induced oxidative stress parameters [serum malondialdehyde (MDA) and serum nitric oxide (NO)] were also estimated by using a UV spectrophotometer. Quantitative estimations of oxygen-sensing proteins (serum EPO and serum VEGF) were done by using the ELISA kit method. The results were expressed as mean ± standard deviation (SD). The correlation between the variables was done using Spearman\'s correlation. A p-value <0.05 was considered statistically significant. Results Adiposity indices and vascular stiffness parameters were found to be significantly (p <0.05) increased in group 2 and group 3 compared to group 1. The levels of serum MDA were found to be significantly (p<0.05) increased in group 2 and group 3 than group 1, whereas the levels of serum NO were significantly (p<0.05) decreased in group 3 and group 2 than group 1. A significant (p<0.05) positive correlation was observed between the PWV and EPO (r=0.492) while a significant (p<0.05) negative correlation was observed between PWV and VEGF (r=-0.406) among the study population. Conclusion The results are indicative of the influence of vascular stress in stage I and II hypertensive patients. Furthermore, the relationship between oxygen-sensing proteins and vascular stress in hypertensive patients has also been established.

Nitric oxide (NO) is involved in the pathogenesis of cerebral ischemic injury. Here, we investigated the effects of aging on NO production during cerebral ischemia-reperfusion (IR). Male Wister rats (WRs) were assigned to 12-month-old (older; n = 5) and 3-month-old (younger; n = 7) groups. Similarly, male spontaneous hypertensive rats (SHRs) were allocated to 12-month-old (older; n = 6) and 3-month-old (younger; n = 8) groups. After anesthesia, their NO production was monitored using in vivo microdialysis probes inserted into the left striatum and hippocampus. Forebrain cerebral IR injuries were produced via ligation of the bilateral common carotid arteries, followed by reperfusion. The change in the NO3- of the older rats in the SHR groups in the striatum was less compared to that of the younger rats before ischemia, during ischemia, and after reperfusion (p < 0.05). In the hippocampus, the change in the NO3- of the older rats in the SHR groups was lower compared to that of the younger rats after reperfusion (p < 0.05). There were no significant differences between the two WR groups. Our findings suggested that aging in SHRs affected NO production, especially in the striatum, before and during cerebral ischemia, and after reperfusion. Hypertension and aging may be important factors impacting NO production in brain IR injury.

Diabetic foot ulcers are a common complication that occurs in approximately 15 percent of patients with diabetes mellitus. Over 60% of diabetic foot ulcers are caused by underlying neuropathy. Former studies on diabetic animals with foot wounds found that vibration platforms significantly accelerate wound healing by catalyzing epithelization, promoting angiogenesis, and enhancing muscle bulk. This result suggests that there is evidence that vibrations may accelerate diabetic neuropathic ulcer healing in human patients. However, to the best of our knowledge, the effect of vibration on the enhancements of diabetic foot ulcer healing in human patients is rarely investigated. Hence, in this work, we conducted an experimental study with human subjects to investigate whether vibration therapy, as a complement to the standard wound treatment, can accelerate the wound healing rate of diabetic neuropathic foot ulcers. In this prospective experimental study, 80 participants diagnosed with Wagner grades I−III diabetic neuropathic foot ulcers were randomly distributed to experimental (n = 40) and control groups (n = 40). Patients in the intervention group received standard wound treatment and vibration wound therapy (VWT), whereas patients in the control group retrieved only standard wound treatment. The results (p = 0.024, α = 0.05) show notable differences in the median healing rate between the intervention group (25 days, 95% CI: 20.3−29.7) and control group (33 days, 95% CI: 25.6−40.4), with the effect-size r, Cohen’s d, Glass’s Δ, and Hedges’ g, respectively, being 0.810, 2.764, 2.311, and 2.772. Moreover, the nitric oxide (NO) level, wound closure area, and wound healing score after intervention significantly differed between the two groups (p < 0.05), putting the intervention group on a higher level than the control group. Furthermore, positive associations were found between the NO level and wound healing closure rates. These findings suggested that VWT enhances diabetic neuropathic foot ulcer healing in terms of healing rate, wound closure area, healing score, and elevated NO level. Considering that no clinically adverse effects were found in the patients induced with vibration intervention, VWT can be regarded as a complementary therapy to the existing ones to accelerate the healing of DFUs.

Background: Cadmium (Cd) is a toxic heavy metal used in many industries. Since the second half of the 20th century, legislation on Cd use was put to limit the exponential rise in its environmental levels. This study aimed to investigate Cd\'s functional and ultrastructural changes on rats\' reproductive systems and the role of Zingiber officinale (Ginger) in protecting against Cd-induced toxicity. Methods: Thirty adult male albino rats were randomly assigned into three equal groups (n = 10); control, Cd-exposed/untreated, and Cd-exposed/Gin-treated. Rat testes were weighed, and testicular tissue sections were examined under the electron microscope. Semen analysis, morphological examination of spermatozoa, and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were measured. In addition, testicular tissue homogenates were analyzed for malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) levels. Results: Cd-induced significant reduction in the mean testicular weight and GSH levels and plasma testosterone, LH and FSH levels with a concomitant increase in testicular MDA and NO levels. There was also a deterioration in semen analysis parameters and spermatozoa morphology, with testicular structural damage in the form of architecture distortion and necrosis of seminiferous tubules and testicular interstitial cells. Daily administration of ginger for 4 weeks protected against CD-induced toxicity, preserving tissue architecture, improved plasma levels of testosterone, LH and FSH and testicular levels of GSH, and reduced testicular levels of MDA, NO. Conclusion: Ginger has a protective effect on Cd-induced deterioration of testicular tissue\'s structural and functional integrity by improving testicular tissue antioxidant capacity and steroid production, which ameliorates sex hormone levels in the blood.

To prepare bioactive peptides with high angiotensin-I-converting enzyme (ACE)-inhibitory (ACEi) activity, Alcalase was selected from five kinds of protease for hydrolyzing Skipjack tuna (Katsuwonus pelamis) muscle, and its best hydrolysis conditions were optimized using single factor and response surface experiments. Then, the high ACEi protein hydrolysate (TMPH) of skipjack tuna muscle was prepared using Alcalase under the optimum conditions of enzyme dose 2.3%, enzymolysis temperature 56.2 °C, and pH 9.4, and its ACEi activity reached 72.71% at 1.0 mg/mL. Subsequently, six novel ACEi peptides were prepared from TMPH using ultrafiltration and chromatography methods and were identified as Ser-Pro (SP), Val-Asp-Arg-Tyr-Phe (VDRYF), Val-His-Gly-Val-Val (VHGVV), Tyr-Glu (YE), Phe-Glu-Met (FEM), and Phe-Trp-Arg-Val (FWRV), with molecular weights of 202.3, 698.9, 509.7, 310.4, 425.6, and 606.8 Da, respectively. SP and VDRYF displayed noticeable ACEi activity, with IC50 values of 0.06 ± 0.01 and 0.28 ± 0.03 mg/mL, respectively. Molecular docking analysis illustrated that the high ACEi activity of SP and VDRYF was attributed to effective interaction with the active sites/pockets of ACE by hydrogen bonding, electrostatic force, and hydrophobic interaction. Furthermore, SP and VDRYF could significantly up-regulate nitric oxide (NO) production and down-regulate endothelin-1 (ET-1) secretion in HUVECs after 24 h treatment, but also abolish the negative effect of 0.5 μM norepinephrine (NE) on the generation of NO and ET-1. Therefore, ACEi peptides derived from skipjack tuna (K. pelamis) muscle, especially SP and VDRYF, are beneficial components for functional food against hypertension and cardiovascular diseases.

Whether meconium-stained amniotic fluid (MSAF) serves as an indicator of fetal distress is under debate; however, the presence of MSAF concerns both obstetricians and pediatricians because meconium aspiration is a major contributor to neonatal morbidity and mortality, even with appropriate treatment. The present study suggested that thick meconium in infants might be associated with poor outcomes compared with thin meconium based on chart reviews. In addition, cell survival assays following the incubation of various meconium concentrations with monolayers of human epithelial and embryonic lung fibroblast cell lines were consistent with the results obtained from chart reviews. Exposure to meconium resulted in the significant release of nitrite from A549 and HEL299 cells. Medicinal agents, including dexamethasone, L-Nω-nitro-arginine methylester (L-NAME), and NS-398 significantly reduced the meconium-induced release of nitrite. These results support the hypothesis that thick meconium is a risk factor for neonates who require resuscitation, and inflammation appears to serve as the primary mechanism for meconium-associated lung injury. A better understanding of the relationship between nitrite and inflammation could result in the development of promising treatments for meconium aspiration syndrome (MAS).

GP.Mur, a red blood cell (RBC) hybrid protein encoded by glycophorin B-A-B, increases expression of erythroid band 3 (Anion Exchanger-1, SLC4A1). GP.Mur is extremely rare but has a prevalence of 1-10% in regions of Southeast Asia. We unexpectedly found slightly higher blood pressure (BP) among healthy Taiwanese adults with GP.Mur. Since band 3 has been suggested to interact with hemoglobin (Hb) to modulate nitric oxide (NO)-dependent hypoxic vasodilation during the respiratory cycle, we hypothesized that GP.Mur red cells could exert differentiable effects on vascular tone. Here we recruited GP.Mur-positive and GP.Mur-negative elite male college athletes, as well as age-matched, GP.Mur-negative non-athletes, for NO-dependent flow-mediated dilation (FMD) and NO-independent dilation (NID). The subjects were also tested for plasma nitrite and nitrate before and after arterial occlusion in FMD. GP.Mur+ and non-GP.Mur athletes exhibited similar heart rates and blood pressure, but GP.Mur+ athletes showed significantly lower FMD (4.8 ± 2.4%) than non-GP.Mur athletes (6.5 ± 2.1%). NO-independent vasodilation was not affected by GP.Mur. As Hb controls intravascular NO bioavailability, we examined the effect of Hb on limiting FMD and found it to be significantly stronger in GP.Mur+ subjects. Biochemically, plasma nitrite levels were directly proportional to individual band 3 expression on the red cell membrane. The increase of plasma nitrite triggered by arterial occlusion also showed small dependency on band 3 levels in non-GP.Mur subjects. By the GP.Mur comparative study, we unveiled comodulation of NO-dependent vasodilation by band 3 and Hb, and verified the long-pending role of erythroid band 3 in this process.

Hormonal changes associated with pregnancy promote oral bacterial growth, which may affect salivary nitric oxide (NO) levels, oxidative stress (OS), and antioxidant capacity (AC). We hypothesized that caries-related bacterial load, NO level, and OS in the saliva change with advancing gestation. The aim of this study was to investigate longitudinal changes in salivary NO, OS, and AC during pregnancy and correlate them with Streptococcus mutans (SM) and Lactobacillus (LB) colonization at different stages of pregnancy. We assessed NO level by Griess method, OS by measuring malondialdehyde (MDA), AC by ABTS radicals and bacterial load by culturing SM and LB in the saliva of pregnant women (n = 96) and compared with non-pregnant women (n = 50) as well as between different stages of pregnancy. Compared with non-pregnant women, NO was 77% higher (4.73 ± 2.87 vs. 2.67 ± 1.55 µM; p < 0.001), MDA was 13% higher (0.96 ± 0.27 vs. 0.85 ± 0.22 nM; p = 0.0055), and AC was 34% lower (60.35 ± 14.33 vs. 80.82 ± 11.60%; p < 0.001) in the late third trimester. NO increased with advancing gestation, but AC and OS did not change significantly during pregnancy. SM were more abundant in pregnant women compared with non-pregnant (p = 0.0012). Pregnancy appears to have an adverse impact on oral health emphasizing the importance optimal oral healthcare during pregnancy.

UNASSIGNED: The Indonesian INOVASIA study is an ongoing multicentre randomized, open controlled trial of pravastatin for the prevention of preeclampsia in patients deemed to be high risk. Here we evaluate the effects of pravastatin on circulating inflammatory and endothelial markers, i.e. Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Endothelin-1 (ET-1), and Nitric Oxide (NO).
UNASSIGNED: Pregnant women deemed to be at a high risk of developing preeclampsia women were recruited based on the Fetal Medicine Foundation preeclampsia screening test or a history of preterm preeclampsia, or clinical risk factors in combination with an abnormal uterine artery Doppler flow pattern at 11-20 week\'s gestation. This is a nested cohort study within the larger trial (INOVASIA); 38 patients were consecutively recruited and assigned to the pravastatin group and the control group. Participants in the pravastatin group received pravastatin (2 × 20 mg p.o) in addition to a standard regimen of aspirin (80 mg p.o) and calcium (1 g p.o), from 14 to 20 weeks until delivery. Blood samples to measure the various biomarkers were obtained in consecutive patients before starting the research medication and just before delivery (pre and post-test examination).
UNASSIGNED: The number of samples on the 2 time points for the various biomarkers was: VEGF: 38, IL-6: 30, ET-1: 38, and NO: 35. IL-6 levels decreased significantly in the pravastatin group (mean ± SD): (191.87 ± 82.99 vs. 151.85 + 48.46, p = .013), while levels in the control group did not change significantly (median (interquartile range)) (144.17 (53.91) vs. 140.82 (16.18), p = .177). ET-1 levels decreased significantly in the pravastatin group (3.64 ± 0.85 vs. 3.01 ± 0.74, p = .006) while the control group had more or less stable levels (3.57 ± 1.12 vs. 3.78 ± 0.73 p = .594). NO was the only serum marker that showed significant changes in both groups. NO levels increased in pravastatin group (11.30 (17.43) vs. 41.90 (53.18), p = .044) and decreased in control group (38.70 (34.80) vs. 10.03 (26.96), p = .002). VEGF levels appeared to follow opposite trends in the 2 groups (NS) (Pravastatin: 3.22 (0.62) vs. 3.28 (0.75), p = .402. Control: 3.38 (0.83) vs. 3.06 (0.74), p = .287).
UNASSIGNED: Administration of 40 mg pravastatin resulted in an improvement in NO levels, and a decrease in IL-6 and endothelin (ET-1) levels. The direction of the effect of pravastatin on these biomarkers appears to underpin the potential for a beneficial effect of pravastatin in the prevention of preeclampsia.

Natural products have served as primary remedies since ancient times due to their cultural acceptance and outstanding biodiversity. To investigate whether Tamarix aphylla L. modulates an inflammatory process, we carried out bioassay-guided isolation where the extracts and isolated compounds were tested for their modulatory effects on several inflammatory indicators, such as nitric oxide (NO), reactive oxygen species (ROS), proinflammatory cytokine; tumour necrosis factor (TNF-α), as well as the proliferation of the lymphocyte T-cells. The aqueous ethanolic extract of the plant inhibited the intracellular ROS production, NO generation, and T-cell proliferation. The aqueous ethanolic crude extract was partitioned by liquid-liquid fractionation using n-hexane (n-C6H6), dichloromethane (DCM), ethyl acetate (EtOAc), n-butanol (n-BuOH), and water (H2O). The DCM and n-BuOH extracts showed the highest activity against most inflammatory indicators and were further purified to obtain compounds 1-4. The structures of 3,5-dihydroxy-4\',7-dimethoxyflavone (1) and 3,5-dihydroxy-4-methoxybenzoic acid methyl ester (2) from the DCM extracts; and kaempferol (3), and 3-hydroxy-4-methoxy-(E)-cinnamic acid (4) from the n-BuOH extract were elucidated by different spectroscopic tools, including MS, NMR, UV, and IR. Compound 2 inhibited the production of ROS and TNF-α, whereas compound 3 showed inhibitory activity against all the tested mediators. A better understanding of the potential aspect of Tamarix aphylla L. derivatives as anti-inflammatory agents could open the door for the development of advanced anti-inflammatory entities.