Nitric Oxide Levels Research Articles

Exploring pathogenic pathways in carpal tunnel syndrome: sterile inflammation and oxidative stress.

The main objective of the current study was to find the association between oxidative stress, inflammatory markers, and electrophysiological profile with symptom severity in patients of carpal tunnel syndrome (CTS). Thirty-two carpal tunnel syndrome patients and 32 controls were included in the study. Boston CTS questionnaire along with plasma oxidative stress markers including superoxide dismutase, malondialdehyde, and nitric oxide and inflammatory markers including IL-6 and TNF-α were compared with the electrophysiological parameters derived from nerve conduction studies. Statistical significance of the levels between groups was calculated using unpaired-t test after checking for normality with D'Agostino & Pearson omnibus normality test. We found that the median nerve conduction velocity was prolonged, amplitude was decreased, while the levels of oxidative stress markers like malondialdehyde (MDA), superoxidase dismutase (SOD), and nitric oxide (NO) were increased in CTS patients compared to controls. Inflammatory markers like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were also increased in CTS patients. We found that plasma SOD and TNF-α correlated well with the median motor amplitude. There was no other significant correlation between oxidative stress markers and inflammatory markers with nerve conduction studies or disease severity. Patients with mild disease also showed lesser levels of SOD, NO, IL-6, and TNF-α markers than patients with severe disease. CTS is probably a disease of sterile inflammation and disbalance of oxidative stress, with higher inflammatory and oxidative stress markers pointing to a more severe disease.

Acetyl-L-carnitine Improves Depressive-like Behaviors Through Nitric Oxide Modulation in the Cuprizone Intoxication Mouse Model of Multiple Sclerosis

Background: Demyelination and inflammation are the most common pathobiological manifestations contributing to depression in multiple sclerosis (MS). Objectives: The current study aimed to evaluate the effects of acetyl-L-carnitine (ALC) in attenuating depressive-like symptoms in the cuprizone intoxication mouse model. Methods: C57BL/6 mice were categorized into three groups (n = 6 each) as follows: The control animals (CTL), the cuprizone-intoxicated mice (CPZ), and the group that received cuprizone and acetyl-L-carnitine (CPZ+ALC). Depressive-like behaviors were evaluated by the forced swim test (FST) and the tail suspension test (TST). The prefrontal cortex (PFC) and corpus callosum (CC) areas were assessed in terms of histopathology, biochemistry, and gene expression. Results: Following oral gavage of ALC, the immobility time, which represents the despairing time, significantly decreased compared to the CPZ group. Histopathological evaluation showed that remyelination in the CC increased significantly in animals receiving ALC compared to the CPZ mice. Acetyl-L-carnitine considerably decreased the nitric oxide (NO) level in the PFC of the brain in the demyelinated mice compared to the CPZ group. The qRT-PCR results revealed that ALC significantly increased neuronal nitric oxide synthase (nNOS) expression but decreased inducible nitric oxide synthase (iNOS) gene expression compared to the CPZ group. Conclusions: ALC attenuated depressive-like behaviors in the cuprizone demyelination mouse model of MS. These neuroprotective effects of ALC may be exerted by facilitating the remyelination process and modulating the NO level in the PFC.

Analysis of non-physiological shear stress-induced red blood cell trauma across different clinical support conditions of the blood pump.

Systematic research into device-induced red blood cell (RBC) damage beyond hemolysis, including correlations between hemolysis and RBC-derived extracellular vesicles, remains limited. This study investigated non-physiological shear stress-induced RBC damage and changes in related biochemical indicators under two blood pump clinical support conditions. Pressure heads of 100 and 350mmHg, numerical simulation methods, and two in vitro loops were utilized to analyze the shear stress and changes in RBC morphology, hemolysis, biochemistry, metabolism, and oxidative stress. The blood pump created higher shear stress in the 350-mmHg condition than in the 100-mmHg condition. With prolonged blood pump operation, plasma-free hemoglobin and cholesterol increased, whereas plasma glucose and nitric oxide decreased in both loops. Notably, plasma iron and triglyceride concentrations increased only in the 350-mmHg condition. The RBC count and morphology, plasma lactic dehydrogenase, and oxidative stress across loops did not differ significantly. Plasma extracellular vesicles, including RBC-derived microparticles, increased significantly at 600min in both loops. Hemolysis correlated with plasma triglyceride, cholesterol, glucose, and nitric oxide levels. Shear stress, but not oxidative stress, was the main cause of RBC damage. Hemolysis alone inadequately reflects overall blood pump-induced RBC damage, suggesting the need for additional biomarkers for comprehensive assessments.

Barbaloin Protects Pentylenetetrazol-Induced Cognitive Deficits in Rodents via Modulation of Neurotransmitters and Inhibition of Oxidative-Free-Radicals-Led Inflammation

Background: Epilepsy is defined by an excessive level of activity in the neurons and coordinated bursts of electrical activity, resulting in the occurrence of seizure episodes. The precise cause of epileptogenesis remains uncertain; nevertheless, the etiology of epilepsy may involve neuroinflammation, oxidative stress, and malfunction of the neurotransmitter system. Objective: The goal of this investigation was to assess barbaloin’s protective properties with respect to pentylenetetrazol (PTZ)-)-induced cognitive deficits in rats via antioxidative, anti-inflammatory, and neurotransmitter-modulating effects. Methods: Wistar rats were subjected to PTZ [40 mg/kg (i.p.)], which induced cognitive decline. Behavior assessment using a kindling score, open-field test (OFT), novel object recognition test (NORT), and assays for superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA), acetylcholinesterase (AChE), caspase-3, nitric oxide (NO), interleukins-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, nuclear factor kappa-B (NF-κB), Bcl-2 and Bax, and neurotransmitter levels [GABA, DA, NE, and serotonin (5-HT)] were performed. Results: The treatment of rats with barbaloin resulted in behavior improvement and significant changes in the levels of GSH, SOD, CAT, MDA, AChE, NO, IL-6, IL-1β, TNF-α, NF-κB, caspase-3, Bcl-2, and Bax compared to the PTZ control group. Barbaloin treatment resulted in notable changes in neurotransmitter levels (GABA, NE, 5-HT, DA) compared to the PTZ group. Conclusions: The ongoing study has gathered evidence indicating that the injection of barbaloin has resulted in significant improvements in cognitive performance in rats. This is achieved by inhibiting oxidative stress, enhancing the activity of natural antioxidant enzymes, reducing cytokine levels, and increasing the levels of neurotransmitters in the brain. These results were detected in comparison to a PTZ control and can be attributed to the potent anti-inflammatory and antioxidant capabilities of barbaloin, which could be linked to its neuroprotective properties. Barbaloin may potentially increase cognitive decline and boost neuronal survival by altering the expression of Bax, caspase-3, Bcl-2.

Mir-605-3p prevents liver premetastatic niche formation by inhibiting angiogenesis via decreasing exosomal nos3 release in gastric cancer.

Cancer-induced pre-metastatic niches (PMNs) play a decisive role in promoting metastasis by facilitating angiogenesis in distant sites. Evidence accumulates suggesting that microRNAs (miRNAs) exert significant influence on angiogenesis during PMN formation, yet their specific roles and regulatory mechanisms in gastric cancer (GC) remain underexplored. miR-605-3p was identified through miRNA-seq and validated by qRT-PCR. Its correlation with the clinicopathological characteristics and prognosis was analyzed in GC. Functional assays were performed to examine angiogenesis both in vitro and in vivo. The related molecular mechanisms were elucidated using RNA-seq, immunofluorescence, transmission electron microscopy, nanoparticle tracking analysis, enzyme-linked immunosorbent assay, luciferase reporter assays and bioinformatics analysis. miR-605-3p was screened as a candidate miRNA that may regulate angiogenesis in GC. Low expression of miR-605-3p is associated with shorter overall survival and disease-free survival in GC. miR-605-3p-mediated GC-secreted exosomes regulate angiogenesis by regulating exosomal nitric oxide synthase 3 (NOS3) derived from GC cells. Mechanistically, miR-605-3p reduced the secretion of exosomes by inhibiting vesicle-associated membrane protein 3 (VAMP3) expression and affects the transport of multivesicular bodies to the GC cell membrane. At the same time, miR-605-3p reduces NOS3 levels in exosomes by inhibiting the expression of intracellular NOS3. Upon uptake of GC cell-derived exosomal NOS3, human umbilical vein endothelial cells exhibited increased nitric oxide levels, which induced angiogenesis, established liver PMN and ultimately promoted the occurrence of liver metastasis. Furthermore, a high level of plasma exosomal NOS3 was clinically associated with metastasis in GC patients. miR-605-3p may play a pivotal role in regulating VAMP3-mediated secretion of exosomal NOS3, thereby affecting the formation of GC PMN and thus inhibiting GC metastasis.

Nobiletin derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone, inhibits neuroinflammation through the inhibition of TLR4/MyD88/MAPK signaling pathways and STAT3 in microglia

Objective: Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3′,4′-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia. Materials and Methods: By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1β, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model. Results: 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model. Conclusions: Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders.

Antioxidant, antidiabetic, and anti-inflammatory activities of flavonoid-rich fractions of Solanum anguivi Lam. fruit: In vitro and ex vivo studies

Diabetes mellitus is a major, rapidly growing endocrine disorder in most countries. The high cost and side effects of conventional drugs for the management of this disease have shifted attention to medicinal plants. Solanum anguivi (S. anguivi) fruits has been reported to be a very good and rich source of polyphenols such as flavonoids, that can be exploited. Flavonoids are plant secondary metabolites widely found in vegetables, fruits and seeds and are known to be of medicinal significance in different range of diseases like diabetes. This study involved in vitro and ex vivo assays on the antioxidant, anti-inflammatory, and antidiabetic properties of flavonoid-rich fractions of S. anguivi fruits. Healthy male Wistar rats (n = 5) weighing 150–180 g were used for ex vivo antioxidant and antidiabetic studies, their liver was exercised for the experiment. The percentage yields of the three flavonoid-rich fractions (Fr. A, B, and C) of S. anguivi fruits obtained from the column chromatographic technique were 15.53 ± 0.75, 11.53 ± 0.80, and 10.17 ± 0.49 mg/g quercetin equivalents. The three fractions (A, B, and C) of S. anguivi fruits significantly scavenged both 2,2-diphenyl-1-picrylhydrazyl (DPPH) with fraction A having the lowest IC50 value (26.14 ± 1.06 μg/ml) compared with fraction B (37.78 ± 5.12 μg/ml) and fraction C (38.24 ± 2.40 μg/ml) when compared with ascorbic acid with the least IC50 value (15.27 ± 0.34 μg/ml). While fraction A (19.61 ± 1.19 μg/ml) scavenged nitric oxide (NO) radicals better than fraction B (22.97 ± 0.55 μg/ml) and fraction C (49.95 ± 6.18 μg/ml). Although ascorbic acid had better scavenging ability than the three fractions (17.23 ± 0.16 μg/ml). The flavonoid-rich fraction A shows better result in inhibiting α-glucosidase with IC50 value of 16.24 μg/ml compared to fraction B (128.04 μg/ml) and fraction C (143.16 μg/ml). For α-amylase, flavonoid-rich fraction A had an IC50 of 31.50 μg/ml compared to B (84.32 μg/ml) and C (145.40 μg/ml). The various controls also showed promising results with acarbose having IC50 of 3.93 μg/mL and 15.66 μg/mL respectively for α-glucosidase and α-amylase. Our findings also showed that FeSO4-induced tissue damage decreased the levels of GSH, SOD, and CAT activities while increasing the levels of MDA. In contrast, following treatment with the three flavonoid fractions of S. anguivi fruits helped to restore these parameters to near-normal levels, by significantly increasing the potential of GSH, SOD, CAT and reducing the levels of MDA which signifies that flavonoid-rich fractions of S. anguivi have great potential to address complications arising from oxidative stress. In addition, the three flavonoid-rich fractions A, B, and C of S. anguivi fruits exhibited ex vivo anti-inflammatory properties via reduced nitric oxide levels in iron-induced oxidative damage. Data obtained from this study shows that the flavonoid-rich fraction of S. anguivi possess anti-diabetic property via inhibition of α-glucosidase and α-amylase and antioxidant property via free radical scavenging. Also, comparing all the fractions, flavonoid-rich fraction A appears to be more potent compared to the fractions B and C. Further research will be needed in isolating and as well applying the fractions in real life situations in the management of diabetes.

Sildenafil Effect on Atrial Natriuretic Peptide Level in Pulmonary Hypertensive Rats.

Pulmonary Hypertension (PH) leads to changes in pulmonary vascular architecture, hypertrophy of the right ventricle, and heart failure. Sildenafil is a drug that can modulate PH by inducing smooth muscle relaxation and vasodilation. To investigate the ability of sildenafil to alleviate the monocritaline (MCT)-induced PH in rats and to estimate the role and its effect on the atrial natriuretic peptide (ANP) levels. 28 adult male rats were divided randomly into four groups: Group A (control group; n=7). Group B (MCT-treated group; n=7) was given a single dose of MCT 60 mg/kg subcutaneously. Group C (The reversal group; n=7) received a single dose of MCT 60 mg/kg subcutaneously for three weeks and then sildenafil at 50 mg/kg/day, given daily for another three weeks. Group D (The prevention group; n=7) simultaneously received a single dose of MCT 60 mg/kg subcutaneously and sildenafil daily at 50 mg/kg for three weeks. The animals in the prevention group showed a significant decrease in ANP levels compared to the reversal and MCT-treated groups. This decrease was associated with a significant reduction in the Fulton index ratio in the prevention group compared to the reversal group. The nitric oxide levels were also significantly higher in the reversal group than in the control group. Preventive sildenafil treatment was associated with a significant decrease in ANP levels and reduced MCT-induced cardiac hypertrophy in rats.

The beneficial effect of fluoxetine on behavioral and cognitive changes in chronic experimental Chagas disease unveils the role of serotonin fueling astrocyte infection by Trypanosoma cruzi.

In Chagas disease (CD), a neglected tropical disease caused by the parasite Trypanosoma cruzi, the development of mental disorders such as anxiety, depression, and memory loss may be underpinned by social, psychological, and biological stressors. Here, we investigated biological factors underlying behavioral changes in a preclinical model of CD. In T. cruzi-infected C57BL/6 mice, a kinetic study (5 to 150 days postinfection, dpi) using standardized methods revealed a sequential onset of behavioral changes: reduced innate compulsive behavior, followed by anxiety and depressive-like behavior, ending with progressive memory impairments. Hence, T. cruzi-infected mice were treated (120 to 150 dpi) with 10 mg/Kg/day of the selective serotonin reuptake inhibitor fluoxetine (Fx), an antidepressant that favors neuroplasticity. Fx therapy reversed the innate compulsive behavior loss, anxiety, and depressive-like behavior while preventing or reversing memory deficits. Biochemical, histological, and parasitological analyses of the brain tissue showed increased levels of the neurotransmitters GABA/glutamate and lipid peroxidation products and decreased expression of brain-derived neurotrophic factor in the absence of neuroinflammation at 150 dpi. Fx therapy ameliorated the neurochemical changes and reduced parasite load in the brain tissue. Next, using the human U-87 MG astroglioma cell line, we found no direct effect of Fx on parasite load. Crucially, serotonin/5-HT (Ser/5-HT) promoted parasite uptake, an effect increased by prior stimulation with IFNγ and TNF but abrogated by Fx. Also, Fx blocked the cytokine-driven Ser/5-HT-promoted increase of nitric oxide and glutamate levels in infected cells. We bring the first evidence of a sequential onset of behavioral changes in T. cruzi-infected mice. Fx therapy improves behavioral and biological changes and parasite control in the brain tissue. Moreover, in the central nervous system, cytokine-driven Ser/5-HT consumption may favor parasite persistence, disrupting neurotransmitter balance and promoting a neurotoxic environment likely contributing to behavioral and cognitive disorders.

Correlation Between Serum microRNA-18a Level and Endothelial Function and Prognosis in Female Coronary Heart Disease Patients.

The aim was to analyze the correlation between serum microRNA (miR)-18a level, endothelial function, and prognosis in female coronary heart disease (CHD) patients. One hundred sixtyfemale patients admitted to our hospital for the first occurrences of chest pain and tightness were divided into CHD and non-CHD groups based on the coronary angiography results. Clinical data, laboratory indexes, serum miR-18a level, and endothelial function [flow-mediated dilation (FMD) function, endothelin 1 (ET-1), and nitric oxide (NO)] were compared. There were no significant differences in clinical data (except CHD family history) between 2 groups. Coronary heart disease group had significantly lower levels of NO and FMD, while significantly higher levels of miR-18a and ET-1 than non-CHD group (P <.05). Pearson correlation showed that serum miR-18a level was positively correlated with ET-1 (r = 0.492, P <.001), and negatively correlated with NO and FMD (r = -0.504, -0.307, P <.001). The receiver operating characteristic) curve showed that the area under the curve of serum miR-18a level in predicting the occurrence of CHD in women was 0.878 (95% CI: 0.828-0.928). Compared with good prognosis group, poor prognosis group had signifi-cantly lower NO, and FMD levels, while higher proportions of acute coronary syndrome, multivessel disease, miR-18a, and ET-1 levels (P <.05). The expression of serum miR-18a in female CHD patients was high, which was related to endothelial function. The increase in serum miR-18a level was a risk factor for the occurrence of MACE in female CHD patients during follow-up, and the serum miR-18a level could effectively predict the occurrence of CHD in female patients.

Effect of Hydrotherapy and Physical Activity on Uric Acid and Nitric Oxide Concentrations in Serum Samples

Hydrotherapy is highly recommended for older adults because it offers warmth and support, so people with pain or reduced mobility and balance can move and exercise more freely compared to regular physical activity. The high plasma antioxidant capacity of uric acid in neutralizing oxidative species and the importance of nitric oxide (NO) in vasodilation and inflammatory response are relevant in older adults. This work aimed to evaluate hydrotherapy's effect on uric acid and NO concentrations in a population aged ≥ 60 years before and after hydrotherapy. A randomized study with 37 individuals was divided into two groups: the experimental group, which was evaluated at two time points: T0-before treatment and T1-after 15-hydrotherapy sessions, and the control group, which did not practice any exercise. The determinations of uric acid and NO levels in serum were carried out by spectrophotometry. Statistics were carried out with SPSS. The experimental group showed a significant increase in the concentration of uric acid in T1 compared to T0. NO results did not show significant differences between T0 and T1. Regular hydrotherapy increases the concentration of serum uric acid, potentially beneficial in the performance of antioxidant functions, reducing oxidative stress, delaying aging, and improving the well-being of older adults.

Aegeline attenuates TNBS-induced colitis by suppressing the NFƙB-mediated NLRP3 inflammasome pathway in mice.

A chronic inflammatory condition of the intestine, ulcerative colitis (UC), is challenging to successfully manage once diagnosed. Currently, available medical therapies for UC exhibit minimal efficacy with unacceptable side effects, while inventive biological agents are expensive and yetnotwell accepted by patients. Discovering more effective and safer treatments to treat UC is therefore essential. One of the primary alkaloids found in Aegle marmelos, aegeline, has anti-inflammatory and antioxidant properties as well as being able to suppress severalpro-inflammatory cytokines responsible for inflammation. The study aimed to investigate the effectiveness of aegeline in alleviating 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis through the NFƙB-mediated NLRP3 inflammasome pathway. Mice were randomly allocated into six groups, Normal control (NC), Model control (MC-TNBS, 2,4,6-trinitrobenzene sulfonic acid), STD (TNBS + sulfasalazine 100mg/kg), AG1, AG2, and AG3 (TNBS + aegeline 5, 10, 20mg/kg) respectively. Physical parameters such as a change in body weight, stool consistency, rectal bleeding, colon length, myeloperoxidase (MPO) levels and nitric oxide (NO) levels, and disease activity index (DAI) were assessed and supporting gene expression studies of various pro-inflammatory cytokines and enzymes were evaluated and histopathological changes observed. Administration of aegeline (10, 20mg/kg) was found to be effective in colon protection by lowering the disease activity score and myeloperoxidase level and improving other physical parameters. Aegeline in high dose significantly downregulated the gene expression of NFƙB, iNOS, COX-2, NLRP3, IL-1β, and IL-18, conferring great anti-inflammatory potential. Suggestive of the findings, aegeline reduced the damage to the colon by downregulating transcriptional genes and enzymes leading to inflammation and mitigated TNBS-induced colitis probably through the NFƙB-mediated NLRP3 inflammasome pathway.

Development of Biologically Active Phytosynthesized Silver Nanoparticles Using Marrubium vulgare L. Extracts: Applications and Cytotoxicity Studies.

Metal nanoparticle phytosynthesis has become, in recent decades, one of the most promising alternatives for the development of nanomaterials using "green chemistry" methods. The present work describes, for the first time in the literature, the phytosynthesis of silver nanoparticles (AgNPs) using extracts obtained by two methods using the aerial parts of Marrubium vulgare L. The extracts (obtained by classical temperature extraction and microwave-assisted extraction) were characterized in terms of total phenolics content and by HPLC analysis, while the phytosynthesis process was confirmed using X-ray diffraction and transmission electron microscopy, the results suggesting that the classical method led to the obtaining of smaller-dimension AgNPs (average diameter under 15 nm by TEM). In terms of biological properties, the study confirmed that AgNPs as well as the M. vulgare crude extracts reduced the viability of human gingival fibroblasts in a concentration- and time-dependent manner, with microwave-assisted extracts having the more pronounced effects. Additionally, the study unveiled that AgNPs transiently increased nitric oxide levels which then decreased over time, thus offering valuable insights into their potential therapeutic use and safety profile.

Harmine exhibits anti-apoptotic properties and reduces diabetes-induced testicular damage caused by streptozotocin in rats.

Diabetes mellitus induces fertility problems in men, mainly because of increased free radicals. Natural resources are effective for male infertility treatment. This study investigated the effects of harmine, an alkaloid available in Peganum harmala L., on the male reproductive system of diabetic rats. We divided 32 rats into four groups, and eight were randomly placed in each group. For diabetes induction, the animals received 50 mg/kg of streptozotocin intraperitoneally. After 1 week, animals received 15 mg/kg of harmine (28 days; intraperitoneal). Histopathological examinations, serum levels of male hormones, levels of nitric oxide (NO) and malondialdehyde (MDA) in the testes, total antioxidant capacity (TAC), insulin serum levels, fasting blood glucose levels, the apoptotic index, and semen analysis were assessed. The diabetes group exhibited morphological changes in testicular tissue, significant decreases in the diameter of the seminiferous tubule, the Johnsen score, testosterone, luteinizing hormone, follicle-stimulating hormone, insulin serum levels, and TAC in testicular tissue (p<0.01). Harmine treatment ameliorated the morphological changes in the testes and improved sperm parameters relative to the diabetes group (p<0.05). The NO and MDA levels in the testes, fasting blood glucose serum levels, and apoptotic index parameters were significantly elevated in the diabetes group, while in the diabetes+harmine group, these parameters were reduced (p<0.01). Harmine protects testicular tissue and sperm against diabetes-induced damage. This effect of harmine is associated with a rebalancing of the antioxidant capacity that subsequently decreases apoptosis in the testes.

Testing of Anti-EMT, Anti-Inflammatory and Antibacterial Activities of 2',4'-Dimethoxychalcone.

Chalcone (1,3-diaryl-2-propen-1-one) is an α, β-unsaturated ketone that serves as an active constituent or precursor of numerous natural substances, exhibiting a broad spectrum of pharmacological effects. In this study, the classical Claisen-Schmidt condensation method was used to synthesize the chalcone derivative 2',4'-dimethoxychalcone (DTC) and evaluate its pharmacological activity. By upregulating the expression of the epithelial cell marker E-cadherin and downregulating the expression of the mesenchymal cell marker vimentin, DTC was found to inhibit transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) process in A549 cells, maintaining the cells' epithelial-like morphology and reducing the ability of the cells to migrate. Additionally, DTC demonstrated the ability to decrease the expression levels of nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in RAW264.7 cells, suggesting a possible anti-inflammatory effect. Furthermore, DTC was found to exhibit bacteriostatic activity against Staphylococcus aureus (S. aureus), Proteus vulgaris (P. vulgaris), methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans (C. albicans), indicating that this chemical may possess broad-spectrum antibacterial activity.

Fluid dynamics and leukocyte transit in the lymphatic system

Abstract The lymphatic system plays a vital role in maintaining fluid balance in living tissue and serves as a pathway for the transport of antigen, immune cells and metastatic cancer cells. Here, we investigate how the movement of cells through a contracting lymphatic vessel differs from steady flow using a lattice Boltzmann-based computational model. Our model consists of cells carried by flow in a 2D vessel with regularly spaced, bi-leaflet valves that ensure net downstream flow as the vessel walls contract autonomously in response to calcium and nitric oxide levels regulated by stretch and shear stress levels. The orientation of the vessel with respect to gravity, which may oppose or assist fluid flow, significantly modulates cellular motion due to its effect on the contraction dynamics of the vessel, even when the cells themselves are neutrally buoyant. Additionally, our model shows that cells are carried along with the flow, but when the vessel is actively contracting, they move faster than the average fluid velocity. We also find that the fluid forces cause significant deformation of the compliant cells, especially in the vicinity of the valves. Our study highlights the importance of considering the complex, transient flows near the valves in understanding cellular motion in lymphatic vessels.

Parkinson’s disease with anxiety: clinical characteristics and their correlation with oxidative stress, inflammation, and pathological proteins

ObjectiveThis study was performed to explore the differences in the clinical characteristics and oxidative stress indicators, inflammatory factors, and pathological proteins in serum between Parkinson’s disease (PD) with anxiety (PD-A) and with no anxiety (PD-NA) patients, and further correlations among clinical characteristics and above variables were analyzed in PD-A and PD-NA groups.MethodsA total of 121 patients with PD were enrolled in this study and assessed by the Hamilton Anxiety Scale (14 items) (HAMA-14). These patients were divided into PD-A and PD-NA groups according to a cut-off point of 7 of HAMA-14. Demographic variables were collected, and clinical symptoms were assessed by multiple rating scales. The levels of free radicals, inflammatory factors, and pathological proteins in serum were measured by chemical colorimetric method and enzyme-linked immunosorbent assay (ELISA). The differences of above variables were compared between PD-A and PD-NA groups, and the correlations of clinical symptoms with the abovevariables were analyzed in PD-A and PD-NA groups.ResultsThe frequency of PD-A was 62.81%. PD-A group exhibited significantly impaired motor dysfunction and multiple non-motor symptoms, including fatigue, sleep behavior disorder, restless leg syndrome and autonomic dysfunction, and dramatically compromised activities of daily living compard with PD-NA group. PD-A group displayed prominently increasedlevels of hydroxyl radical (·OH) and tumor necrosis factor (TNF)-α, and a decreased nitric oxide (NO) level in serum compared with PD-NA group (P<0.001, P = 0.001, P= 0.027, respectively). ·OH, NO, and TNF-α were identified as the risk factors of PD-A (OR = 1.005, P = 0.036; OR = 0.956, P = 0.017; OR = 1.039, P = 0.033, respectively). In PD patients, HAMA-14 score was significantly and positively correlated with the levels of ·OH and TNF-α in serum (P<0.001, P = 0.002, respectively). In PD-A group, ·OH level was significantly and negatively correlated with Aβ1−42 level, while TNF-α level was significantly and positively correlated with P-tau (S396) level in serum.ConclusionsThe frequency of PD-A is high. PD-A patients present more severe motor dysfunction and multiple non-motor symptoms, and poorer activities of daily living. The increased levels of ·OH and TNF-α levels and the decreased NO level in serum are all associated with more severe anxiety in PD patients.Findings from this study may provide in-depth insights into the clinical characteristics, underlying mechanisms of PD-A, and potential correlations among anxiety, oxidative stress, inflammation, and cognitive decline in PD patients.

Ameliorative Effect of Teucrium polium Extract against Nicotine Induced Liver Toxicity in Swiss Albino Mice

Background: Nicotine can be consumed in many forms, the most common of which is smoking tobacco. Tobacco smoking is a global problem that negatively affects human health. Natural plants are vital antioxidants that may antagonize the toxic effects of smoking. We designed the present study to assess the protective potential of Teucrium polium extract (TPE) on nicotine-induced liver toxicity in male mice. Methods: Twenty-four animals were allocated into four equal groups and daily treated for 21 constitutive days. Control group one received distilled water, group two orally received 100 mg/kg TPE, group three received subcutaneous injections of 2.5 mg/kg nicotine and group four received 100 mg/kg TPE orally then 2.5 mg/kg nicotine subcutaneously after one hour. Result: Nicotine exposure significantly elevated liver enzymes; alanine transaminase (ALT) and aspartate transaminase (AST). The levels of malondialdehyde (MDA) and nitric oxide (NO) were also elevated along with a reduction in glutathione reduced content (GSH), superoxide dismutase (SOD) and catalase (CAT) activity. Treatment with TPE considerably ameliorated the serum levels of liver enzymes, lowered MDA and NO levels, as well as elevated the antioxidant defense system. Also, TPE improved the histological structure and modulated apoptosis caused by nicotine. The current study proved the effectiveness of TPE as a natural antioxidant for the alleviation of nicotine-induced hepatic biochemical and histopathological alterations through attenuating oxidative stress, improving antioxidant systems and abrogating apoptosis.

Nigella sativa, active principle thymoquinone, alleviates palmitate-induced cytotoxicity, inflammation and bioenergetic disruptions in macrophages: An invitro study model

Thymoquinone (TQ) is one of the main phytochemical bioactive ingredients in Nigella sativa, with reported immunity-boosting properties. The current study evaluated the anti-inflammatory effect of TQ against inflammation brought on by free fatty acid Palmitate (PA) using macrophages raw 264.7 cell line. Data revealed that TQ significantly improved the viability of basal and PA stimulated Macrophages at concentrations of 50 and 100 μg/mL. Also, TQ significantly reduced nitric oxide and triglyceride levels in PA-stimulated macrophages at concentrations of 50 and 100 μg/mL. The pro-inflammatory cytokines studies revealed that PA significantly increased the release of the cytokines TNF-α, MHGB-1, IL-1β, and IL-6. TQ at concentrations 25, 50, and 100 μg/ml significantly decreases the release of the studied cytokines in PA-stimulated macrophages to variable extents with parallel inhibition to their corresponding gene expression. Bioenergetic assays showed that PA significantly decreased cellular ATP, mitochondrial complexes I and III activities and mitochondrial membrane potential with a subsequent significant increase in lactate production. At the same time, TQ can alleviate the effect of PA on macrophages' bioenergetics parameters to variable extent based on TQ concentration. To conclude, TQ could mitigate palmitate-induced inflammation and cytotoxicity in macrophages by improving macrophage viability and controlling cytokine release with improved PA-induced bioenergetics disruption.

Tumor Microenvironment-Activatable Phototheranostic: Leveraging Nitric Oxide and Weak Acidity as Dual Biomarkers for Ratiometric Fluorescence, Photoacoustic Imaging, and Photothermal Therapy.

Tumor microenvironment-responsive phototheranostic agents are highly sought after for their ability to improve diagnostic accuracy and treatment specificity. Here, we introduce a novel single-molecule probe, POZ-NO, which is activated by nitric oxide (NO) and weak acidity, enabling dual-mode imaging and photothermal therapy (PTT) of tumors. In acidic environments with elevated NO levels, POZ-NO exhibits a distinctive ratiometric fluorescence signal shift from the red to near-infrared, accompanied by a 700 nm photoacoustic signal. Additionally, POZ-NO demonstrated potent photothermal effects upon NO and acidity activation, achieving an impressive conversion efficiency of 74.3% under 735 nm laser irradiation. In vivo studies confirm POZ-NO's ability to accurately image tumors through ratiometric fluorescence and photoacoustic modes while selectively treating tumors with PTT.