Nitric Oxide Levels Research Articles

Effect of low-molecular-weight heparin calcium combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function and pregnancy outcome in early-onset severe preeclampsia.

This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient's blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment.

The Role of Inducible Nitric Oxide Synthase in Assessing the Functional Level of Coronary Artery Lesions in Chronic Coronary Syndrome.

Chronic coronary syndrome (CCS) is a long-term manifestation of coronary artery disease, marked by stable but recurring chest pain and myocardial ischemia due to the gradual buildup of atherosclerotic plaques in the coronary arteries. It is a metabolic disorder of coronary arteries characterized by oxidative stress, endothelial dysfunction, inflammation, and hyperlipidemia. The imbalance in oxidative-antioxidative status contributes to stable ischemic heart disease. Oxidative stress involves reactive oxygen and nitrogen species, leading to low-density lipoprotein (LDL) oxidation. Endothelial dysfunction, marked by reduced nitric oxide (NO) bioavailability, is an early onset of CCS, affecting vasodilation, cell proliferation, and inflammatory responses. Enzyme myeloperoxidase (MPO), traditionally considered protective, plays a dual role in initiating and progressing inflammatory diseases. MPO interacts with NO, modulating its catalytic activity. Elevated NO levels inhibit MPO through a reversible complex formation, preventing NO-induced inhibition by inducible nitric oxide synthase (iNOS). MPO also inactivates endothelial nitric oxide synthase (eNOS) and reacts with L-arginine, hindering NO synthesis. The interplay between MPO and NO significantly influences inflammation sites, impacting peroxidation rates and oxidation reactions. Peroxynitrite, a reactive species, contributes to nitration of tyrosine residues and lipid peroxidation. Mechanistic pathways suggest MPO enhances iNOS catalytic activity, influencing CCS development. iNOS, implicated in inflammation and atherosclerosis, is connected to NO regulation. This review analyzes the complex interplay of MPO, iNOS, and NO that affects plaque morphology, oxidative stress, and inflammation, contributing to atherosclerosis progression. Therefore, it is possible that the phenotypes of atherosclerotic plaques, focal and diffuse coronary artery disease, could be defined by the relationship between MPO and iNOS.

Chrysin Enhances Anti-Cancer Activity of Jurkat T Cell and NK-92 Cells Against Human Breast Cancer Cell Lines.

Chrysin, a naturally occurring flavonoid in plant and bee products, demonstrates notable biological activities, including anti-cancer effects. These properties are partially attributed to its capability to activate immune cells. This study focused on exploring the immunomodulatory potential of chrysin on NK-92 and Jurkat-T cells targeting breast cancer cells (BCC). Chrysin leads to activation of NK-92 and T cells facilitated by the addition of human recombinant IL-2 and PHA-M. The anti-cancer efficacy of chrysin on these immune cells was evaluated in a co-culture setup with EGF-stimulated MCF-7 and MDA-MB-231 cells. Findings revealed that chrysin notably increased the cytotoxicity of NK-92 and T cells towards MCF-7 and MDA-MB-231 cells, with the most significant impact observed on MCF-7 cells (20 %). The activation of NK-92 cells, marked by increased IFN-γ production and CD56 expression, correlated with enhanced secretion of cytokines. Additionally, the activation of these cells against BCC was linked with elevated levels of granzyme-B, TNF-α, and nitric oxide (NO). Similarly, the cytotoxic activation of Jurkat-T cells against BCC was characterized by increased production of granzyme-B, IL-2, and IFN-γ. Consequently, these results support the hypothesis that chrysin significantly contributes to the activation and functional enhancement of NK-92 and T-cells against two distinct BCC lines.

Investigation of blood pressure regulatory effect of bioactive peptides in complex enzyme-assisted hydrolysate from Paralichthys olivaceus

This study aimed to identify the bioactive peptides of protamex-pepsin hydrolysate obtained from Paralichthys olivaceus (POppH) and to investigate their potential vasorelaxation and blood pressure regulatory properties, both in vitro and in vivo. The effects of the peptides on endothelium-derived relaxing factors (EDRFs), such as nitric oxide and hydrogen sulfate levels, were analyzed in EA.hy926 cells, and the vasorelaxation-related PI3K/AKT/eNOS pathway activity was analyzed in EA. hy926 cells. An in vitro study revealed that POppH and leucine-glutamic acid-arginine (IER) peptide did not show any cytotoxic effects and significantly increased EDRF production via the regulation of vasorelaxation-associated PI3K/AKT/eNOS protein expression in EA.hy926 cells. An in vivo study suggested that oral administration of IER reduced systolic, diastolic, and mean arterial blood pressure in a spontaneously hypertensive rat model. The bioactive peptide IER derived from Paralichthys olivaceus could be used in the development of functional food products with blood pressure regulatory properties.

Aloe ferox leaf gel extracts attenuate redox imbalance in oxidative renal injury and stimulates glucose uptake, whilst inhibiting key enzymes linked to diabetes and obesity

The worldwide prevalence of diabetes and obesity is growing rapidly. Both metabolic disorders are linked to chronic adverse complications, which include kidney dysfunctions. Medicinal plants play a crucial role in traditional healthcare, especially in developing countries. Aloe ferox, native to South Africa, has a long history of medicinal use, but its pharmacological potential is less studied compared to other Aloe species, necessitating further investigation. Therefore, the present study was conducted to determine the antioxidative, anti-obesogenic, and antidiabetic effects of A. ferox leaf gel extracts using in vitro, ex vivo, and in silico experimental models, with oxidative renal damage induced by ferrous sulfate (FeSO4). A. ferox leaf gel extracts exhibited strong antioxidant activity, inhibited digestive enzymes, and significantly improved glucose uptake. The aqueous extract demonstrated better antioxidant efficacy, leading to higher reduced glutathione (GSH) level, and superoxide dismutase (SOD) and catalase enzymes activity, along with a concurrent reduction of nitric oxide (NO) and malondialdehyde (MDA) levels. Likewise, the aqueous extract showed more potent in vitro DPPH, NO, and OH• radical scavenging activity with IC50 values of 3.64 ±0.3 μg/mL, 110.73±0.1 μg/mL, and 331.13 ±0.7 μg/mL, respectively. The aqueous extract had better inhibition of the enzyme α-amylase (IC50 = 25.73±2.5 µg/mL), whilst the ethanolic extract inhibited α-glucosidase (IC50 =663.2±0.3 µg/ml), and pancreatic lipase (IC50 =122.01±5.9 µg/mL) more strongly. Incubation of the extracts with yeast cells stimulated glucose uptake dose dependently, when ethanolic extract (IC50 = 308.01±0.7 µg/mL) showed the better activity compared to the aqueous extract (IC50 = 338.79±7.05 µg/mL). Furthermore, LC-MS analysis led to the identification of many compounds, when chlorogenic acid demonstrated a stronger molecular interaction with the active site amino acids of α-amylase and catalase compared to other compounds. However, Aloin B showed the highest affinity with α-glucosidase and 5-Hydroxyaloin A showed the lowest binding energy with lipase, and SOD enzyme. These results suggest the reno-protective effects of A. ferox leaf gel extracts against FeSO4-induced oxidative stress along with its anti-hyperglycaemic activity. Given these observed effects, A. ferox leaf gel could indeed be valuable in developing natural therapies and potential drug development for the management of these disorders. Further studies in animal models are needed to ascertain the results of this study.

Nitric Oxide Levels in Primary Hypertension Patients Receiving Wet Cupping Therapy

Wet cupping has been shown in several studies to lower blood pressure in hypertensive patients. However, the mechanism of action remains unknown, limiting its use as a complementary non-pharmacological treatment. This study aims to examine the effect of wet cupping on systolic blood pressure, diastolic blood pressure, and nitric oxide levels in hypertensive patients. The study employed a quasi-experimental method with a pretest and post-test design, including a control group. The sample consisted of 40 individuals, they were diagnosed with primary grade I hypertension. The participants were divided into two groups (treatment and control). The intervention group received wet cupping therapy twice, at a 28-day interval, while continuing their antihypertensive medication. The control group only consumed antihypertensive medication. The study revealed a significant decrease in systolic and diastolic blood pressure but no significant increase in nitric oxide levels. After the intervention, the systolic blood pressure in the intervention group decreased by 17.69 mmHg (p=0.010), compared to a decrease of 5.87 mmHg (p=0,108) in the control group, with a difference of (p=0.010). The diastolic blood pressure in the treatment group decreased by 11.56 mmHg (p=0.000), compared to a decrease of 0.73 mmHg (p-0.570) in the control group, with a difference of (p=0.001). The nitric oxide levels in the intervention group increased by 2.5 µmol/L (p=0.530), compared to a decrease of 0.47 µmol/L (p=0.116), in the control group, with a difference of (p=0.539). It can be concluded that wet cupping therapy reduces systolic and diastolic blood pressure but does not significantly increase nitric oxide levels in the blood of hypertensive patients.

Intranasal Administration of Standardized Extract of Gotu Kola Leaves Against Nitroglycerine-Induced Recurrent Migraine-Like Pain in Rats

The present study aimed to determine the efficacy of intranasal administration of a standardized extract of Gotu kola, i.e., Centella asiatica (L.) Urban (INDCA-NS) with marker triterpenoids for the prevention of nitroglycerine- (NTG)-induced recurrent migraine in rats. Adult rats of both sexes in a group of 12 were administered intraperitoneal NTG (10 mg/kg) on alternate days (D1 to D9) and once daily intranasal solutions of either vehicle (saline, 50 µL/rat/day), sumatriptan (80 µL/rat/day of 12 mg/ml) as positive control, or INDCA-NS (10, 30, or 100 µg/rat/day) for 21 days. Behavioral and biochemical parameters related to concurrent migraine pain (facial expressions on the grimace scale, thermal hyperalgesia, mechanical allodynia, and plasma and brain levels of pituitary adenylate cyclase-activating polypeptide and nitric oxide), and stress (photophobia and cortisol levels in the brain and serum) were measured. The intranasal administration of INDCA-NS prevented NTG-induced migraine-like pain, photophobia, and stress in a dose-dependent manner. At the same time, sumatriptan alleviated pain and anxiety but not photophobia. In conclusion, the intranasal administration of INDCA-NS showed prophylactic efficacy against recurrent NTG-induced migraine pain in rats.

Evaluation of anti-hypertensive activity of Quercus leucotrichophora A. camus methanolic extract on DOCA-salt induced hypertensive rats

Quercus leucotrichophora A. camus, commonly known as Banj oak or Ban tree, belongs to the Fagaceae family and is abundantly found in the regions of Shimla, Kullu-Manali, and upper Mandi in Himachal Pradesh. This study explores the medicinal properties of plant seeds, known for their antioxidant and diuretic activity, traditionally utilized in the treatment of hypertension and hypolipidemic, hepatoprotective conditions. PurposeTo investigate the antihypertensive effect of methanolic extract of Quercus leucotrichophora A. camus seeds in DOCA sat induced rats. Material and methodsGround seeds of Quercus leucotrichophora A. camus were stored in an airtight container. A total of 100 gs of dried seed powder were subjected to extraction using 250 ml of methanol and a Soxhlet extractor maintained at 60–65 °C for five hours. The resulting dried extract (5 gs) was stored in an airtight container in a refrigerator at low temperature and administered by rats to test its antihypertensive impact. The assessment of obtained extract impact on hypertension induced by DOCA-salt was conducted through blood pressure measurement and biochemical analysis. ResultsOur study revealed that the methanolic extract of Quercus leucotrichophora A. camus seeds exerted blood pressure-lowering effects, associated with an increase in serum Nitric Oxide (NO) levels. The attenuation of hypertension by extract was further linked to the normalization of serum Na+ and K+concentrations, indicating an improvement in electrolyte imbalance. Additionally, the antioxidant properties of Quercus leucotrichophora A. camus were evident through increased activities of Glutathione (GSH), Glutathione Peroxidase (GHPx), Superoxide Dismutase (SOD), and decrease activity of Thiobarbituric acid reactive substances (TBARS). ConclusionThe findings of our investigation suggest that the antihypertensive action of Quercus leucotrichophora A. camus is correlated with enhanced endothelial nitric oxide synthase (eNOS) activation and an augmented antioxidant defense system. This sheds light on the potential therapeutic benefits of plant under investigation in managing hypertension, emphasizing its role in promoting cardiovascular health. Further research is warranted to elucidate the underlying mechanisms and to explore the full pharmacological potential of Quercus leucotrichophora A. camus in the field of cardiovascular medicine.

Single acute and repeated subacute toxicity evaluations of Annona atemoya leaf extract with in vitro anti-inflammatory potential

The nutraceutical and biological potential of Annona atemoya, a fruiting plant, has been reported. We and others have demonstrated that A. atemoya leaf extract (AAL) has various pharmacological properties, such as antioxidant, antimicrobial, and neuroprotective effects. However, knowledge about the safety and potential toxicity of AAL remains limited. We aimed to assess the potential toxicity of AAL using acute and repeated subacute oral toxicity tests in rats. In both acute and repeated subacute toxicity test, no AAL-related behavioral abnormalities or changes in mortality, food intake, body weight were observed up to a dosage of 2000 mg/kg, indicating that the median lethal dose of AAL is higher than 2000 mg/kg. In subacute toxicity tests, no significant changes in hematological and biochemical parameters, urinalysis results, and histopathological variables were observed. Therefore, the no-observed-adverse-effect level (NOAEL) of orally administered AAL was estimated to be 2000 mg/kg/day in male and female rats. We also examined the effect of AAL on the inflammatory reaction in lipopolysaccharide (LPS)-stimulated BV-2 cells. AAL treatment significantly inhibited the LPS-stimulated increases in the levels of nitric oxide (NO) and inflammatory cytokines, implying that AAL has an anti-inflammatory effect. Quality control analysis revealed that two marker compounds, rutin and isoquercitrin, were present at 27.570 and 4.322 mg/g, respectively, in a freeze-dried AAL sample and were completely eluted within 27 min. The extraction recovery was 99.47–103.80%, and the precision was ≤2.79%. Overall, these findings suggest the safety, anti-inflammatory activity, and standardization of AAL.

Exploring the hepatoprotective potential of the probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide-postbiotic on ibuprofen-induced acute liver injury in rats.

The present study investigates the hepatoprotective effect of a probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide (EPS) against ibuprofen-induced acute liver injury, and to explore the involved underlying mechanisms. Hepatotoxicity was induced by administration of a single dose of ibuprofen (200 mg/kg body weight). The Lpb. plantarum E1K2R2 (109 CFU) and its EPS (200 mg/kg bw) were separately used to feed rats for seven consecutive days before ibuprofen administration. Liver toxicity was assessed by monitoring levels of serum liver enzymes, liver relative weight, oxidative stress and inflammatory markers, and through histopathological analysis. The results showed that ibuprofen administration significantly increased (P < 0.05) liver relative weight, elevated levels of alanine-amino transferase (ALT), aspartate-amino transferase (AST), decreased hepatic gluthatione (GSH) and endogenous antioxidant enzymes including, superoxide dismutase (SOD), catalase (CAT) and increased malondialdehyde (MDA) levels, nitric oxide (NO) and myeloperoxidase (MPO) in hepatic tissues. However, pre-treatment with Lpb. plantarum E1K2R2 and its EPS significantly attenuated these toxicity manifestations. Both pre-treatments restored liver weight, normalized transaminase enzyme levels, enhanced the activity of liver antioxidant enzymes (SOD and CAT), increased GSH content, and significantly reduced NO, MPO and MDA levels (P < 0.05), indicating their protective role against oxidative stress and inflammatory response induced by ibuprofen. Furthermore, histopathological analysis confirmed regular liver morphology in rats pre-treated with the probiotic and its EPS. These findings highlight the potential effectiveness of the probiotic Lpb. plantarum E1K2R2 and its EPS in mitigating ibuprofen-induced liver toxicity.

A water-soluble mycelium polysaccharide from Monascus pilosus: Extraction, structural characterization, immunomodulatory effect and yield enhanced by overexpression of UGE gene

Mycelium polysaccharide (MPP) from Monascus pilosus with the compositions of glucose, galactose, mannose, glucosamine hydrochloride, rhamnose and arabinose, was obtained using alkaline extracting, and subsequently three purified components (MPP-0, MPP-0.1 and MPP-0.3) were separated. The purity and extraction volume of the MPP-0.1 fraction surpassed those of the other two groups, thus warranting its selection for subsequent experimental investigations. The sample MPP-0.1, with an average molecular weight of 3.7776 × 104 Da, exhibited exceptional thermal stability up to 170 °C. The main glycosidic linkage pattern of MPP-0.1 was structured as→[4)-α-D-Glcp-(1]6 → 4)-α-D-Glcp-(1 → [2)-α-D-Manp-(1]5 → 2)-α-D-Manp-(1 → 5)-β-D-Galf-(1 → 3)-β-D-Galf (1 → 3)-β-D-Galf-(1 → 3)-β-D-Galf-(1→, and branched Glcp, Manp, Galf fragments were connected with the main chain through →4, 6)-α-D-Glcp-(1→, →2, 6)-α-D-Manp-(1 → and →3, 6)-β-D-Galf-(1→. Besides, the up-regulated levels of Nitric oxide (NO), Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β) and other pro-inflammatory cytokines along with increased phagocytic activity revealed that MPP-0.1 has significant immunomodulatory effect, and can significantly enhance the proliferation and activation of RAW264.7 cells. Finally, the gene UGE (UDP-glucose 4-epimerase) was overexpressed in M. pilosus to increase the MPP production. Results showed that the biomass of the recombinant strain exhibited a remarkable increase of approximately 62.56 ± 1.50 % compared to that of the parental strain, and the extraction yield of MPP increased significantly by 83.19 ± 4.56 %.

Chondroitin Sulfate from Halaelurus burgeri Skin Inhibits Hepatic Endoplasmic Reticulum Stress and Inflammation, and Regulates Gut Microbiota.

Previous study has demonstrated the chemical structure of chondroitin sulfate (CHS) from Halaelurus burgeri skin and its effects on insulin resistance. However, the precise impact of this phenomenon on endoplasmic reticulum (ER) stress and inflammation, which contribute to insulin resistance, remains unclear. This study is to investigate the impact of CHS on ER stress, inflammatory response and signaling, and gut microbiota in high-fat diet (HFD)-fed mice. HFD-fed C57BL/6J mice receive dietary gavage intervention of CHS for 18 weeks. Blood, liver tissue, and feces are harvested for further investigation. Results show that CHS inhibits ER stress, accompanied by lowered blood glucose, nitric oxide (NO), reactive oxygen (ROS), and free fatty acids (FFA) levels, and increases hepatic glycogen accumulation. Moreover, hepatic inflammation is improved by CHS treatment via inactivation of Toll-like receptor 4 (TLR4) signaling and its downstream c-jun N-terminal kinase (JNK) and nuclear factor kappa B (NFκB) pathways. Additionally, CHS regulates gut microbiota, particularly the decline in the Firmicutes to Bacteroidetes ratio. CHS also lowers fecal lipopolysaccharide and elevates several fecal short chain fatty acids. These findings suggest that CHS from H. burgeri skin may be an alternative functional food supplement for anti-ER stress, anti-inflammtion, and regulation of gut microbiota.

Protective role of hesperetin in Drosophila melanogaster model of ferrous sulphate-induced toxicity

The toxicological hazard of iron-containing products is a public health concern that inspires research in identifying and developing readily available, inexpensive antidotes. Natural products, like plant-sourced antioxidants, can be of great value in this regard. Hesperetin a flavonoid abundantly present in citrus fruits is known to possess a diverse pharmacological and antioxidant attribute. The present study investigated the alleviation of detrimental effects of ferrous sulphate (FeSO4) by hesperetin in Drosophila melanogaster. Flies were exposed to FeSO4 (10 µM) alone or supplemented with hesperetin (50 or 100 µM) via diet for 7 consecutive days. Antioxidant enzyme activities, non-enzymatic antioxidant levels, acetylcholinesterase activity and oxidative stress markers were then measured. Hesperetin supplementation significantly (p < 0.05) attenuated FeSO4-induced oxidative stress by enhancement of enzymic antioxidants (catalase and glutathione-S-transferases) activities, preservation of non-enzymic antioxidants (total thiols and non-protein thiols), and reduction of other markers of oxidative stress (hydrogen peroxide, protein carbonyl and lipid peroxidation) in D. melanogaster. In addition, hesperetin supplementation decreased nitric oxide levels and enhanced acetylcholinesterase activity. Furthermore, hesperetin supplementation improved FeSO4-induced locomotor deficit, while there was no significant difference in cell viability (mitochondrial metabolic rate) in the treatment groups. This study suggests that hesperetin might be a promising functional agent in preventing iron toxicity and similar metal-induced impairments.

Impact of Diabetic Condition on the Remodeling of In Situ Tissue-Engineered Heart Valves.

Most in situ tissue-engineered heart valve (TEHV) evaluation studies are conducted in a healthy physical environment, which cannot accurately reflect the specific characteristics of patients. In this study, we established a diabetic rabbit model and implanted decellularized extracellular matrix (dECM) into the abdominal aorta of rabbits through interventional surgery with a follow-up period of 8 weeks. The results indicated that dECM implants in diabetic rabbits exhibited poorer endothelialization and more severe fibrosis compared to those in healthy animals. Furthermore, mechanistic studies revealed that high glucose induced endothelial cell (EC) apoptosis and impeded their proliferation and migration, accompanied by an increase in reactive oxygen species (ROS) concentration and a decrease in the nitric oxide (NO) level. High glucose also led to elevated ROS levels and an increased expression of inflammatory factors and transforming growth factor β1 (TGF-β1) in macrophages, contributing to fibrosis. These findings suggest that oxidative-stress-mediated mechanisms are likely the primary pathways affecting heart valve repair and regeneration under diabetic conditions. Therefore, future design and evaluation of TEHVs may concern more patient-specific circumstances.

Cardiovascular effects of Roflumilast during sepsis: Risks or benefits?

BackgroundPhosphodiesterase-4 (PDE4) is responsible for terminating cyclic adenosine monophosphate (cAMP) signalling. PDE4 inhibitors, such as roflumilast (RFM), have anti-inflammatory activity and have been studied in inflammation-induced tissue damage in sepsis. However, the role of RFM on cardiovascular derangements induced by sepsis is still unknown. Thus, we aimed to evaluate the potential effects of RFM on cardiovascular collapse and multiorgan damage caused by sepsis. MethodsSepsis was induced by cecal ligation and puncture (CLP) in male rats. Six hours after the CLP or sham procedure, animals were randomly assigned to receive either RFM (0.3 mg/kg) or vehicle subcutaneously, and cardiovascular parameters were assessed 24 h after the surgery and organ/plasma samples were collected for further analyses. ResultsSepsis induced hypotension, tachycardia, reduced renal blood flow (RBF) and hyporeactivity to vasoconstrictors both in vivo and ex vivo. RFM treatment increased systemic cAMP levels and RBF. RFM also attenuated hypoperfusion and liver damage induced by CLP. Furthermore, RFM reduced systemic nitric oxide (NO) levels in septic rats, while there were no changes in hepatic NOS-2 expression. Nevertheless, RFM exacerbated sepsis-induced hypotension and tachycardia without ameliorating vascular hyporeactivity. ConclusionOur data show that PDE-4 inhibition protects septic rats from hepatic injury and improves renal perfusion. However, RFM worsened hemodynamic parameters and showed no protection against sepsis-induced cardiovascular dysfunction and mortality. Thus, despite the anti-inflammatory benefits of RFM, its application in sepsis should be approached cautiously.

The role of microenvironmental factors in the pre-ovulatory oocyte in the pathogenesis of “poor” ovarian response to in vitro fertilization (IVF) programs

Background. The “poor” response to ovarian stimulation during IVF (in vitro fertilization) cycles depends on various factors, including the biochemical composition of the follicle microenvironment. Recent studies have focused on the relationship between vascular tone regulators, angiogenic factors, oxidative stress, and the quality of oocytes. Despite this, there is still no consensus on the exact effect of these factors on folliculogenesis or their role in “poor” responses.Objective. To evaluate the content of biochemical factors and regulators of vascular tone and angiogenesis in follicular fluid in patients with a “poor” ovarian response to stimulation in IVF programs, compared to similar indicators in women with a normal ovarian response.Materials and methods. An open prospective cohort study was conducted, including 56 patients who were part of the IVF program. The criterion for separating the cohort of women was their response to controlled ovarian stimulation during the IVF cycle. Women with a “poor” response (n=32) were placed in the main group, while those with a normal response (n=24) were in the comparison group. Follicular fluid samples from women with a “poor” response were divided into two subgroups based on the presence or absence of an oocyte-cumulus complex in the follicle. The biochemical and soluble regulatory factors in follicular fluid were analyzed in both groups after controlled ovarian stimulation was completed. Statistical analysis of the data was done using methods from variation statistics. A critical level of significance for the differences was set at p ≤0.05.Result. The levels of urea, glucose, high-density lipoprotein, and total antioxidant status (TAOS) in follicular fluid (FF) from patients with a “poor” ovarian response were statistically significantly higher compared to those in the control group. The levels of bilirubin, low-density lipoprotein, and uric acid were also significantly lower in VF from patients in the main group compared to the control group, p&lt;0.05. The indices of vascular endothelial growth factor (VEGF-A) and vascular endothelial growth receptor-2 (VEGFR-2) in FF from women with a “poor” response were significantly lower than those from patients with a normal response, while the levels of endogenous nitric oxide were significantly higher in the former group compared to the latter, p&lt;0.05.Conclusion. The absence of an oocyte-cumulus complex in the pre-ovulatory follicle, which is associated with a “poor” response of the ovary to stimulation, is likely due to a disruption in vascularization processes. This is supported by a decrease in the levels of pro- and anti-angiogenic factors, such as VEGF-A and VEGFR-2.

Wearable nitric oxide-releasing antibacterial insert for preventing device-associated infections

Medical device-associated infections are a pervasive global healthcare concern, often leading to severe complications. Bacterial biofilms that form on indwelling medical devices, such as catheters, are significant contributors to infections like bloodstream and urinary tract infections. This study addresses the challenge of biofilms on medical devices by introducing a portable antimicrobial catheter insert (PACI) designed to be efficient, biocompatible, and anti-infective. The PACI utilizes nitric oxide (NO), known for its potent antimicrobial properties, to deter bacterial adhesion and biofilm formation. To achieve this, a photoinitiated NO donor, S-nitroso-N-acetylpenicillamine (SNAP), is covalently linked to a polydimethylsiloxane (PDMS) polymer. This design allows for higher NO loading for long-term impact and prevents premature donor leaching, a common challenge with SNAP-blended polymers. The SNAP-PDMS material was applied to a side-glowing fiber optic and connected to a wearable light module emitting 450 nm light, creating a functional antimicrobial insert. Activation of the fiber optic, accomplished with a one-click mechanism, enables real-time NO release, maintaining controlled NO levels for a minimum of 24 hours. The therapeutic levels of NO released via photocatalysis from the PACI demonstrated remarkable efficacy, with >90 % reduction in bacterial viability against S. aureus, S. epidermidis, and P. mirabilis without any cytotoxic impact on mammalian cells. This study underscores the potential of the NO-releasing insert in clinical settings, providing a portable and adaptable solution for preventing catheter-associated infections.

Positive impact of indicaxanthin from Opuntia ficus-indica fruit on high-fat diet-induced neuronal damage and gut microbiota dysbiosis.

Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet; the high-fat diet group was fed a high-fat diet; and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally (0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet-induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids (Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles (Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet-induced neuronal damage and on the gut microbiota composition in obese mice.

Isolation and Characterization of the Cyanobacterial Macrolide Glycoside Moorenaside, an Anti-Inflammatory Analogue of Aurisides Targeting the Keap1/Nrf2 Pathway.

A new 14-membered ring brominated macrolide glycoside, named moorenaside (1), was discovered from a marine cyanobacterial sample collected from Shands Key in Florida. The structure of 1 was established by analysis of spectroscopic data including its relative configuration. The absolute configuration was inferred from optical rotation data and comparison with related compounds. The structure of 1 features an α,β-unsaturated carbonyl system, which is also found in aurisides. The presence of this motif in 1 prompted us to evaluate its effect on Keap1/Nrf2 signaling, a cytoprotective pathway culminating in the activation of antioxidant genes activated upstream by the cysteine alkylation of Keap1. Moorenaside exhibited moderate ARE luciferase activity at 32 μM. Due to the established crosstalk between Nrf2 and NF-κB pathways, we investigated the anti-inflammatory effects of 1 in LPS-induced mouse macrophages (RAW264.7 cells), a commonly used model for inflammation. Moorenaside significantly upregulated Nqo1 (Nrf2 target gene) and downregulated iNos (NF-κB target gene) at 32 μM by 5.0- and 2.5-fold, respectively, resulting in a significant reduction of nitric oxide (NO) levels. Furthermore, we performed RNA-sequencing and demonstrated the transcriptional activity of 1 on a global level and identified canonical pathways and upstream regulators involved in inflammation, immune response, and certain oxidative-stress-underlying diseases such as multiple sclerosis and chronic kidney disease.

Sodium stress-induced oxidative damage and antioxidant responses during grain filling in Indica rice.

Sodium treatment caused the sodium ion accumulation at the milk stage of immature rice grains which in turn triggered the overproduction of reactive oxygen species and oxidative damage. The tolerant cultivar showed an enhanced antioxidative response and induced expressions of OsNHX and OsHKT ion-transporters. Sodium chloride-(NaCl) induced soil salinity is a major constraint hindering global rice production. Amongst its constituent ions, sodium (Na+) is known to be the main driver of toxicity under salt stress. The present investigation aims to measure the impacts of excess Na+ during rice grain filling using two Indica rice cultivars with opposite tolerances to salt (salt tolerant: Panvel-3, salt-sensitive: Sahyadri-3) mainly via oxidative and responsive antioxidative pathways. Plants were treated with Na+-specific treatments and NaCl with equimolar Na+ levels (100mM) at the initiation of the reproductive phase. Stressed and control plants were harvested at three different grain-filling stages- early milk, milk, and dough and assessed for ion accumulation and oxidative damage/antioxidant responses under Na+ stress. Na+ toxicity triggered reactive oxygen species (ROS) production and upregulated the responsive enzymatic antioxidants. Na+ stress also increased the nitric oxide (NO) levels and the activity of nitrate reductase in immature grains. Differential expression levels of OsNHX and OsHKT transporters were observed in response to Na+ stress. Mature grains displayed a high accumulation of Na+ along with reduced K+ content and elevated Na+/K+ under high Na+ availability. The alterations in mature grains' sugar, starch, and protein content were also observed in response to the Na+ stress. Overall, the salt-tolerant cultivar displayed higher antioxidant activities and a lower rate of ROS generation in response to the Na+ stress. Results suggested a link between Na+ accumulation, Na+-mediated stress responses via anti/-oxidant pathways, and the grain-filling process in both rice cultivars.