Myeloperoxidase Content Research Articles

The Efficacy and Safety of Green-Lipped Mussel Extract Plus Ginkgo Biloba on Anti-Inflammatory Status in Patients with Knee Osteoarthritis

Background: Clinical research on the efficacy of nutraceutical compounds recommended for the relief of osteoarthritis (OA) symptoms has been largely disputed. In addition, no link has been established between its safety and efficacy in Kurdish population. The aim of this study is to determine the efficacy of New Zealand green-lipped mussel extract + Ginkgo biloba (GLME+) in patients with OA, and analyze the effect of GLME+ on inflammation. Methods: In an open-label, single-group allocation study, 40 patients diagnosed with knee OA were administrated 1000 mg/day of New Zealand green-lipped mussel extract and 100 mg/day of Ginkgo biloba for eight weeks. The outcome measure was scored using Western Ontario and McMaster Universities arthritis index (WOMAC). The serum concentration of inflammatory chemokine (CCL3) and myeloperoxidase (MPO) were measured. An intention-to-treat analysis was employed and subject data at T0 and T8 weeks. Results: Results showed a significant improvement in WOMAC score in post-treated OA patients with GLME+ (P<0.001). In addition, CCL3 serum levels were significantly decreased after an 8-week intervention (P<0.001). Moreover, no statistical significance was observed within groups in MPO serum levels (P> 0.05). Conclusions: GLME+ improved knee joint pain, stiffness, and mobility in OA patients. Two of GLME+'s chondroprotective properties were the reduction of oxidative damage and the inhibition of inflammation, both of which have been linked to the etiology of OA cartilage destruction. The findings indicated that GLME+ may be useful in the treatment of OA patients.

Targeting Myeloperoxidase to Reduce Neuroinflammation in X-Linked Dystonia Parkinsonism.

Although the genetic locus of X-linked dystonia parkinsonism (XDP), a neurodegenerative disease endemic in the Philippines, is well-characterized, the exact mechanisms leading to neuronal loss are not yet fully understood. Recently, we demonstrated an increase in myeloperoxidase (MPO) levels in XDP postmortem prefrontal cortex (PFC), suggesting a role for inflammation in XDP pathogenesis. Therefore, we hypothesized that inhibiting MPO could provide a therapeutic strategy for XDP. MPO activity was measured by using an MPO-activatable fluorescent agent (MAFA) in human postmortem PFC. Reactive oxygen species (ROS) and MPO activity were measured in XDP-derived fibroblasts and SH-SY5Y cells following MPO inhibition. MPO activity was significantly increased in XDP PFC. Additionally, treatment of cell lines with postmortem XDP PFC resulted in a significant increase in ROS levels. To determine whether increases in MPO activity caused increases in ROS, MPO content was immunodepleted from XDP PFC, which resulted in a significant decrease in ROS in SH-SY5Y cells. Consistently, the treatment with verdiperstat, a potent and selective MPO inhibitor, significantly decreased ROS in both XDP-derived fibroblasts and XDP PFC-treated SH-SY5Y cells. Collectively, our results suggest that MPO inhibition mitigates oxidative stress and may provide a novel therapeutic strategy for XDP treatment.

Anti-Inflammatory Humulene-Type Sesquiterpenoids from Asteriscus Graveolens

Objectives: Inflammation is the initial physiological reaction of the immune system to infection or irritation, leading significant risk factors for several forms of cancer. The genus Asteriscus has been observed to possess a notable abundance of sesquiterpenes with anti-inflammatory properties. This study was designed to assess the anti-inflammatory activity of the sesquiterpenoids isolated from Asteriscus graveolens. Methods: The organic extract of the Asteraceae plant A. graveolens was subjected to different chromatographic and spectroscopic techniques for isolation, purification, and identification of sesquiterpenoid contents. The isolated compounds were screened for anti-inflammatory activities in two animal models: rat paw edema and rat ear edema. Histopathological examinations as well as biochemical markers of inflammation were assessed. This was followed by in silico screening for anti-inflammatory activity. Results: Four known sesquiterpenoids were isolated from A. graveolens, including two humulene derivatives, namely, 9-oxohumula-4-en-6,15-olide (1), and 9-oxohumula-1(10)(Z),4,7(E)-trien-6,15-olide (2) and two bisabolene derivatives, identified as bisabola-2,10-dien-1-one (3) and 6- hydroxybisabola-2,10-dien-1-one (4) described. In the rat paw edema model, compound 2 showed highest activity in preventing formation carrageenan-induced paw edema. This was confirmed by histopathological examinations that indicated partial preservation of the epidermal and dermal layers. Further, the compound significantly inhibited cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) release. In the croton oil indued rat ear edema, compounds 2 and 4 significantly inhibited ear edema and protected against histopathological alterations. This was associated with prevention of myeloperoxidase (MPO) concentration in ear tissues. Molecular docking and molecular dynamic simulation indicated the affinity and docking stability of compounds 1-4 to the selected inflammatory protein. Conclusion: Phytochemical investigation of A. graveolens resulted in the isolation and characterization of four sesquiterpenes. In particular, compound 2 showed potent anti-inflammatory activity in carrageenan rat paw edema and croton oil ear edema.

Sportomics Analyses of the Exercise-Induced Impact on Amino Acid Metabolism and Acute-Phase Protein Kinetics in Female Olympic Athletes

Background: Exercise can be used as a model to understand immunometabolism. Biological data on elite athletes are limited, especially for female athletes, including relevant data on acute-phase proteins and amino acid metabolism. Methods: We analyzed acute-phase proteins and amino acids collected at South American, Pan-American, and Olympic Games for 16 Olympic sports. We compared female and male elite athletes (447 vs. 990 samples) across four states (fasting, pre-exercise, post-exercise, and resting) to understand sex-specific immunometabolic responses in elite athletes. Results: Considering all states and sports, we found that elite female athletes exhibited higher concentrations of C-reactive protein, lipopolysaccharide-binding protein, myeloperoxidase, haptoglobin, and IGF1, with ratios ranging from 1.2 to 2.0 (p < 0.001). Women exhibited lower concentrations of most amino acids, except for glutamate and alanine. Although almost 30% lower in women, branched-chain amino acids (BCAAs) showed a similar pattern in all states (ρ ≥ 0.9; p < 0.001), while aromatic amino acids (AAAs) showed higher consumption during exercise in women. Conclusion: We established sex dimorphism in elite athletes’ metabolic and inflammatory responses during training and competition. Our data suggest that female athletes present a lower amino acid response towards central fatigue development than male athletes. Understanding these differences can lead to insights into sex-related immuno-metabolic responses in sports or other inflammatory conditions.

PON1 and PON3 in Alzheimer's Disease: Similar Functions but Different Roles.

Paraoxonase 1 (PON1) and Paraoxonase 3 (PON3) are enzymes located on the surface of high-density lipoprotein (HDL) and share similar antioxidant properties, possibly modulated by other proteins such as Myeloperoxidase (MPO), which drives the shift from functional to dysfunctional HDL. PON1 has been extensively studied in relation to Alzheimer's Disease (AD), but the role of PON3 remains unknown. To fill this knowledge gap, the study analyzed PON3 protein levels and PON1-arylesterase activity in 99 AD patients, 100 patients with mild cognitive impairment (MCI), and 79 cognitively normal controls. The results showed that serum PON3 levels remained unchanged across all groups. In contrast, serum arylesterase activity was significantly reduced in both AD and MCI patients compared to controls (p < 0.001 for both comparisons). Surprisingly, there was no correlation between arylesterase activity and MPO protein concentration or activity. However, PON3 was found to have a significant positive correlation with both MPO concentration (r = 0.507, p < 0.0001) and MPO activity (r = 0.264, p < 0.01). In conclusion, we demonstrated for the first time that PON1 and PON3 have distinct relationships with AD, with only PON1 showing a decrease in activity in this disease, while PON3 levels remained unchanged. Another noteworthy finding was the selective correlation between PON3 and MPO, which may suggest a preferential physical association of PON3 with dysfunctional HDL.

A Synbiotic Combining Chitin-Glucan and Lactobacillus acidophilus NCFM Induces a Colonic Molecular Signature Soothing Intestinal Pain and Inflammation in an Animal Model of IBS.

Chitin-glucan (CG) is a new generation of prebiotic. Lactobacillus acidophilus NCFM® (NCFM) is a probiotic with the ability to decrease abdominal pain. We evaluate the functional and molecular gastrointestinal responses to a synbiotic administration combining CG and NCFM in a rat model of long-lasting colon hypersensitivity. The intracolonic pressure was assessed during the 9-week experiment in animals receiving CG in association or not with NCFM and compared to that in Lacticaseibacillus paracasei Lpc-37®-treated animals and control rats receiving tap water. The effects of the synbiotic were evaluated using the Wallace score, the quantification of colon myeloperoxidase (MPO) and the master genes driving analgesia and inflammation. CG 1.5 alone and NCFM 109 colony forming units (CFU) alone similarly decreased the visceral pain sensitivity. Lpc-37 had no significant effect. The best profile of pain perception inhibition was obtained with the combination of CG 1.5 g and NCFM 109 CFU, confirming a synbiotic property. This synbiotic treatment significantly reduced macroscopic colonic lesions and MPO concentrations, and induced master genes involved in analgesia (CB1, CB2, MOR, PPARα), with a downregulation of inflammatory cytokines (IL-1β, TNFα) and an induction of IL-10 and PPARγ. In conclusion, CG 1.5 g + NCFM 109 CFU significantly decreased visceral pain perception and intestinal inflammation through the regulation of master genes.

Double-layer optical fiber interferometer with bio-layer-modified reflector for label-free biosensing of inflammatory proteins

This work discusses label-free biosensing application of a double-layer optical fiber interferometer where the second layer tailors the reflection conditions at the external plain and supports changes in reflected optical spectrum when a bio-layer binds to it. The double-layer nanostructure consists of precisely tailored thin films, i.e., titanium (TiO2) and hafnium oxides (HfO2) deposited on single-mode fiber end-face by magnetron sputtering. It has been shown numerically and experimentally that the approach besides well spectrally defined interference pattern distinguishes refractive index (RI) changes taking place in a volume and on the sensor surface. These are of interest when label-free biosensing applications are considered. The case of myeloperoxidase (MPO) detection—a protein, which concentration rises during inflammation—is reported as an example of application. The response of the sensor to MPO in a concentration range of 1 × 10−11–5 × 10−6 g/mL was tested. An increase in the MPO concentration was followed by a redshift of the interference pattern and a decrease in reflected power. The negative control performed using ferritin proved specificity of the sensor. The results reported in this work indicate capability of the approach for diagnostic label-free biosensing, possibly also at in vivo conditions.

Sulfated polysaccharide extracted from the alga Gracilaria domingensis modified with propionic anhydride negatively modulates acute inflammation and experimental hypernociception

Sulfated polysaccharides (PLSs) from marine algae represent a broad class of compounds with pharmacological interest, due to their therapeutic properties. PLSs have hydrophilic chains containing various chemical groups of several compositions that differ structurally and in their physicochemical and biological effects. However, this hydrophilic nature of PLSs is also responsible for some limitations in the use of these compounds. To overcome these disadvantages, PLSs can be chemically modified by grafting groups that can give the compound a more hydrophobic nature. In the present study, the PLS from Gracilaria domingensis was modified with propionic anhydride (PLS-AP) and underwent complementary characterizations by scanning electron microscopy, X-ray diffraction, infrared spectral analysis and elemental analysis. The reaction with propionic anhydride increased crystallinity and produced a chemically modified polysaccharide with new carbon, hydrogen and sulfur groups. The new characteristic of the compound may have added interesting properties to PLS, such as increased stability, amphiphilic nature and increased sulfate content, which in red marine algae SPSs produce biological activity. Regarding biological properties, PLS-AP (2.5 mg/kg) significantly reduced paw edema induced by carrageenan, histamine, serotonin, bradykinin and prostaglandin E2, as well as improved microscopic tissue damage criteria. The modified compound was also able to significantly decrease neutrophil migration, myeloperoxidase, and malondialdehyde concentrations and preserved glutathione levels in peritoneal fluid during induced peritonitis. Additionally, in antinociceptive tests, PLS-AP reduced the number of contortions induced by acetic acid and the response time to formalin-induced paw licking. Thus, PLS-AP may be a promising substance to treat inflammatory conditions.

Determination of Serum Myeloperoxidase (MPO) and lactate dehydrogenase (LDH) as a tumour Marker in Chronic Myeloid Leukaemia (CML).

To evaluate the efficacy of serum myeloperoxidase and lactate dehydrogenase levels as tumour markers in chronic myeloid leukaemia patients after one-year treatment with tyrosine kinase inhibitors. The case-control study was conducted at the College of Medicine, Mustansiriyah University, Baghdad, Iraq, in collaboration with the National Centre of Haematology, Baghdad, from December 2019 to April 2020. The cases comprised chronic myeloid leukaemia patients aged ≥18 years who had completed one-year treatment with tyrosine kinase inhibitor. They were divided into two groups on the basis of major molecular response. Group 1 patients had major molecular response >0.1%, while group 2 patients had major molecular response <0.1%. Group 3 had healthy controls matched for age and gender. Serum myeloperoxidase and lactate dehydrogenase concentrations were measured using enzyme-linked immunosorbent assay. Data was analysed using SPSS 25. Of the 88 subjects, 32(36.4%) were in group A with mean age 44.9±12.6 years, 26(29.5%) were in group B with mean age 48.23±10.6 years, and 30(34%) were in group C with mean age 43.1±9.3 years. There was a significant increase in myeloperoxidase and lactate dehydrogenase levels in patient groups compared group 3 controls (p<0.05). Between the patient groups 1 and 2, the difference was significant for myeloperoxidase (p<0.05), but not for lactate dehydrogenase (p>0.05). There was higher oxidative stress in chronic myeloid leukaemia patients.

Antibacterial and Healing Efficacy of Mangiferin-Loaded Silver Nanoparticle and Chitosan-Alginate Membrane Dressings

Mangiferin, a bioactive constituent of Mangifera indica (family Anacardiaceae), has an impressive therapeutic profile, having antioxidant, anti-inflammatory, analgesic, antibacterial, and immunomodulatory properties capable of possessing wound healing potential. Our investigation aims to isolate and characterize mangiferin, green synthesis of silver nanoparticles (Ag-NPs) and production of chitosan alginate (Cs/Alg) film dressing loaded with mangiferin Ag-NPs and assess antibacterial and wound-healing properties against infected excision and burn wounds. The isolated mangiferin was authenticated by estimating melting point, thin layer chromatography (TLC), fourier-transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC). Ag-NPs were green synthesized and characterized by UV-visible, particle size, zeta potential (ZP), entrapment efficiency (%EE), scanning electron microscope (SEM), transmission electron microscope (TEM), and stability study. Chitosan alginate membrane dressing was prepared by incorporating mangiferin Ag-NPs, and film thickness, pH, film weight, water intake capacity, and in-vitro drug release parameters were estimated. Among the four mangiferin Ag-NP batches, MN3 formed stable polydispersity spherical Ag-NPs with smaller particle size and high %EE. Mangiferin-loaded Cs/Alg film MN-CM4 showed significantly higher (p &lt; 0.001) drug content, wettability, release profile, and favorable pH changes. The mangiferin Ag-NPs embedded Cs/Alg film dressing showed a significantly high antimicrobial effect against the gram-positive bacterial strain of S. aureus, commonly found in wounds. MN3 and MN-CM4 treatment showed the shortest epithelialization period and enhanced wound closure. The hydroxyproline content has significantly (p &lt; 0.001) increased, and myeloperoxidase content was reduced by MN3 and MN-CM4 treatment. MN-CM4 treatment showed complete re-epithelialization reduced inflammatory cells with thicker and denser collagen fiber deposition. The effectiveness of the Cs/Alg film of mangiferin Ag-NPs dressing has a synergistic effect on promoting speedy wound healing. The Cs/Alg film of mangiferin Ag-NPs showed rapid wound healing against infected and burned wounds, enhanced collagen synthesis, and anti-inflammatory and antibacterial efficacy.

Development and Characterization of Gingerol-Assisted Silver Nanoparticle and Chitosan Alginate Membrane for Antibacterial and Wound Healing Activity.

This study synthesized and characterized gingerol-loaded silver nanoparticles (Ag-NPs), which were incorporated into chitosan-alginate (Cs/Alg) films for advanced wound care applications. Gingerol was isolated with a 9.81% yield, forming pale-yellow needle-shaped crystals with a melting point of 32ºC. The purity and structure of gingerol were confirmed through thin-layer chromatography (TLC), UV-visible, fourier-transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC) analyses. The synthesized Ag-NPs, particularly from the GN3 batch, exhibited a small particle size (36.52 ± 3.52 nm), high stability (zeta potential of -23.20 mV), and notable encapsulation efficiency (76.35%) and yield (74.11%). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses revealed their spherical and smooth morphology. Stability tests over three months showed no substantial changes in particle size, ZP, or %EE. The Cs/Alg films demonstrated appropriate thickness, weight, water uptake, and pH changes, with GN-CM4 showing the best performance. In-vitro drug release studies indicated increased release rates, especially for GN-CM4, which also exhibited the highest antibacterial activity. In-vivo studies on excision and burn wound models showed that GN-CM4 promoted complete wound closure by day 21, enhanced hydroxyproline levels, reduced myeloperoxidase content, and facilitated superior tissue regeneration. These findings underscore the potential of gingerol-loaded Ag-NPs in enhancing wound healing through their anti-inflammatory and antibacterial properties.

Effective action of silymarin against ketamine-induced schizophrenia in male mice: Insight into the biochemical and molecular mechanisms of action

BackgroundNeurochemical dysregulations resulting from N-methyl-D-aspartate hypofunction (NMDA), are exacerbated by neuroimmune and oxidative stress and are known risk factors for neuropsychiatric disorders like schizophrenia-like diseases. Here, we investigate the protective and curative effects, and mechanisms of silymarin, a polyphenolic flavonoid with neuroprotective functions in preventive-reversal model of ketamine, an NMDA antagonist in mice. MethodsMice were grouped into 6 cohorts (n = 9). In the pre-treatment, groups 1 and 2 received saline (10 mL/kg/p.o.), groups 3 and 4 (silymarin, 50 and 100 mg/kg/p.o.), and group 5 (risperidone, 0.5 mg/kg/p.o.) consecutively for 14 days, then combined with ketamine (20 mg/kg/i.p.) injection in groups 2–5 from days 8–14. However, mice in reversal study received intraperitoneal injection of ketamine for 14 days before silymarin (50 and 100 mg/kg, p.o) and risperidone (0.5 mg/kg, p.o.) treatment between days 8–14. The consequences on schizophrenia-like behavior, neurochemistry, inflammation, and oxidative/nitrergic stress markers were evaluated in critical brain regions of the disease. ResultsSilymarin prevented and reversed ketamine-induced increase in dopamine, 5-hydroxyltryptamine, acetylcholinesterase, malondialdehyde and nitrite levels in the striatum, prefrontal-cortex and hippocampus. These were accompanied by improvement in hyperlocomotion, stereotypy, memory, and social impairments, notably devoid of cataleptogenic potential. Complementarily, silymarin reduced myeloperoxidase, tumor-necrosis factor-α, and interleukin-6 concentrations relative to the ketamine group. Moreover, ketamine-induced decreased brain-derived neurotrophic factor, glutathione, catalase, superoxide-dismutase levels were normalized by silymarin in the brain regions relative to ketamine. ConclusionsOverall, these findings suggest that silymarin's antipsychotic effect might be primarily associated, among other mechanisms, with the normalization of neurochemical and neurotrophic changes in the mice brains.

Зміни концентрації sST2, активності мієлопероксидази та iндуцибельної NO-синтази в сироватці крові та лімфоцитах як показник важкості перебігу захворювання у пацієнтів з артеріальною гіпертензією та на тлі коронавірусної хвороби

The prevalence of COVID-19 and its polymorphic clinical manifestations are attributed to a systemic inflammatory response, which also plays a key role in the development of arterial hypertension (AH). The prognosis and effectiveness of treatment in patients with AH and COVID-19 should be assessed based on the levels of inflammatory biomarkers sST2, myeloperoxidase, and iNOS. The aim of the work was to analyze the prognostic value sST2, myeloperoxidase and iNOS levels in the blood serum of patients with arterial hypertension (AH) and COVID-19. Methods. 2 groups of patients were examined: group 1- 36 patients with AH and hypertensive crisis. Group 2 – 35 patients with AH and polysegmental pneumonia on the background of COVID-19. The control group – 16 practically healthy individuals. All patients underwent anthropometry, determination of biochemical blood tests, echocardiography, level of sST2, and activity of iNOS and MPO using ELISA in blood serum and lymphocytes. Results. A 2.4-fold increase in sST2 content in blood serum was noted in AH and 2.9-fold in the background of COVID-19. The level of myeloperoxidase in blood serum increased 2.5 times in hypertension and 3.4 times in coronavirus disease. In lymphocytes, iNOS activity increased 3.25 times in hypertension and 4.3 times in COVID-19. sST2 level has a significant correlation with the size of the left atrium, left ventricle, and ejection fraction in patients with AH. A positive correlation with age was noted in the group of patients with AH and COVID-19. Conclusions. Levels of sST2, iNOS and myeloperoxidase are important markers of the severity of cardiovascular pathology, as well as in COVID-19 patients. In patients with arterial hypertension and in combination with COVID-19, a significant increase in the concentration of sST2, myeloperoxidase and iNOS was observed compared to practically healthy individuals. A significant elevation in myeloperoxidase levels has been noted in patients with AH without coronavirus disease, indicating the utility of its use as a highly sensitive marker for low-intensity inflammation, particularly in arterial hypertension. This makes this marker more promising for use than C-reactive protein.

Cucurbitacin IIb alleviates colitis via regulating gut microbial composition and metabolites

Cucurbitacin IIb, a member of the triterpenoid family, exerts beneficial effects on intestinal diseases, including enteritis and bacillary dysentery. However, its effects and mechanisms of action on colitis have not yet been explored. In this study, we used a mouse model of dextran sulfate sodium (DSS)-induced colitis and explored the effects of cucurbitacin IIb on colitis symptoms, inflammatory responses, microbiota, and metabolite profiles. The results showed that cucurbitacin IIb alleviated colitis symptoms including body weight loss, an increase in the disease activity index, and elevated levels of myeloperoxidase and eosinophil peroxidase content. Additionally, it ameliorated intestinal morphology impairment, reduced the phosphorylation of NFκB protein, and mitigated accumulation of pro-inflammatory cytokines IL-6 and IL-1β. Furthermore, cucurbitacin IIb alleviated alterations in gut microbial composition and metabolites in DSS-treated mice. However, antibiotic treatment diminishes the beneficial effects of cucurbitacin IIb on colitis. We further found that transplantation of fresh feces or heat-inactivated feces from mice treated with cucurbitacin IIb to DSS-treated mice alleviated colitis, similar to the effects of cucurbitacin IIb. Collectively, our results suggest that cucurbitacin IIb exerted anti-inflammatory effects in colitis by regulating the microbiota composition and metabolites, thereby alleviating colitis symptoms.

Nuciferine inhibits TLR4/NF-κB/MAPK signaling axis and alleviates adjuvant-induced arthritis in rats

Rheumatoid arthritis is an inflammatory condition primarily affecting the joints. Nuciferine (NCF), a key bioactive aporphine alkaloid biosynthesized in lotus leaves, exhibits promising anti-inflammatory and antioxidant properties. In this study, we investigated whether NCF could alleviate inflammatory arthritis conditions in a complete Freund's adjuvant (CFA)-mediated arthritis model in rats. The arthritis model was established through intradermal injection of CFA (100 μL) in the sub-plantar region of the right hind paw. The arthritic animals were treated orally with NCF at 5 and 10 mg/kg and indomethacin (Indo) at 5 mg/kg body weight as reference control. NCF treatment remarkably alleviated inflammatory joint swelling and arthritic index. The radiological and histological analysis revealed evidence of the beneficial effects of NCF. NCF treatment decreased the content of pro-inflammatory cytokines (TNF-α and IL-1β) and myeloperoxidase (MPO) activity and restored the anti-inflammatory cytokine (IL-10) in the paw joints. The serum levels of pro-inflammatory cytokines were also markedly reduced in the NCF (10 mg/kg) treatment group. Moreover, the arthritis-induced inflammatory mediators, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the toll-like receptor (TLR)-4, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) signaling proteins were substantially decreased in the NCF treatment groups. NCF treatment also restored the antioxidant defense enzymes and abrogated lipid peroxidation in the paw tissue. Our findings strongly suggest that NCF is a promising therapeutic molecule for rheumatoid arthritis, inspiring further research, and development in this area.

NDRG2 Deficiency Exacerbates UVB-Induced Skin Inflammation and Oxidative Stress Damage.

UVB radiation induces inflammatory and oxidative stress responses, contributing to skin damage, yet the underlying mechanisms are not fully understood. N-Myc downstream-regulated gene 2 (NDRG2), an emerging stress-associated gene, remains unexplored in UVB-induced skin injury. In this study, we detected skin NDRG2 expression after UVB irradiation for the first time and further used Ndrg2 knockout mice to clarify the role of NDRG2 in UVB-induced skin injury. Three-month-old male Ndrg2+/+ and Ndrg2-/- mice (16-18g) were exposed to UVB to induce acute skin damage, and then dorsal skin samples were collected for subsequent analyses. UVB-induced skin damage was scored. Western Blot Analysis, immunofluorescence (IF) double labeling, and immunohistochemistry (IHC) were employed to assess NDRG2 expression and/or distribution. The concentrations of TNF-α, IL-6, IL-1β, MPO, MMP8, superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining were employed to determine pathological changes. RNA sequencing and analysis were performed to estimate transcript expression levels and analyze mRNA expression. DESeq2 software was employed to identify differentially expressed genes (DEGs). DEGs were visualized using volcanic and heat maps. Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed to identify primary biological functions, metabolic pathways, or signal transduction pathways associated with DEGs. UVB-challenged Ndrg2-/- mice exhibited significantly exacerbated skin damage (erythema, edema, and erosion), neutrophil infiltration, and apoptosis compared to Ndrg2+/+ mice. Furthermore, UVB-challenged Ndrg2-/- mice displayed significantly elevated pro-inflammatory cytokines, myeloperoxidase (MPO), matrix metalloproteinase-8 (MMP8), and reduced antioxidant expression. RNA sequencing identified 1091 significantly differentially expressed genes enriched in inflammation, immune response, and oxidative stress pathways. In conclusion, the deficiency of Ndrg2 markedly exacerbated UVB-induced skin damage by promoting inflammatory responses and inhibiting antioxidant responses. This suggests that stabilizing NDRG2 expression holds promise as a therapeutic strategy for protecting against UVB-induced skin damage.

Hesperidin Alleviates Acute Necrotizing Pancreatitis by Activating SIRT1 - Molecular Docking, Molecular Dynamics Simulation, and Experimental Validation.

Acute necrotizing pancreatitis is a serious pancreatic injury with limited effective treatments. This study aims to investigate the therapeutic effects of hesperidin on Larginine- induced acute pancreatitis and its potential targets. The authors induced acute pancreatitis in mice by administering two hourly intraperitoneal injections of L-arginine-HCl, and evaluated the impact of hesperidin on pancreatic and lung tissues, plasma amylase activity, and myeloperoxidase content. Additionally, necrosis and mitochondrial function was tested in primary pancreatic acinar cells. The interactions between hesperidin and proteins involved in necrosis and mitochondrial dysfunction were further invested using in silico molecular docking and molecular dynamic simulations. Hesperidin effectively ameliorated the severity of acute necrotizing pancreatitis by reducing plasma amylase, pancreatic MPO, serum IL-6 levels, pancreatic edema, inflammation, and pancreatic necrosis. Hesperidin also protected against acute pancreatitis-associated lung injury and prevented acinar cell necrosis, mitochondrial membrane potential loss, and ATP depletion. In addition, hesperidin exhibited a high binding affinity with SIRT1 and increased the protein levels of SIRT1. The SIRT1 inhibitor EX527 abolished the protective effect of hesperidin against necrosis in acinar cells. These findings indicate that hesperidin alleviates the severity of acute necrotizing pancreatitis by activating SIRT1, which may provide insight into the mechanisms of natural compounds in treating AP. Hesperidin has potential as a therapeutic agent for acute necrotizing pancreatitis and provides a new approach for novel therapeutic strategies.

Carbon monoxide polyhemoglobin improves the therapeutic effect and relieves inflammation in the colon tissue of haemorrhagic shock/resuscitation rats

Objective The objective of this study was to test the therapeutic effect of carbon monoxide polyhemoglobin (polyCOHb) in haemorrhagic shock/resuscitation and its underlying mechanisms. Methods 48 rats were divided into two experimental parts, and 36 rats in the first experiment and 12 rats in the second experiment. In the first experimental part, 36 animals were randomly assigned to the following groups: hydroxyethyl starch group (HES group, n = 12), polyhemoglobin group (polyHb group, n = 12), and carbon monoxide polyhemoglobin group (polyCOHb group, n = 12). In the second experimental part, 12 animals were randomly assigned to the following groups: polyHb group (n = 6), and polyCOHb group (n = 6). Then the anaesthetised rats were haemorrhaged by withdrawing 50% of the animal’s blood volume (BV), and resuscitated to the same volume of the animal’s withdrawing BV with HES, polyHb, polyCOHb. In the first experimental part, the 72h survival rates of each groups animals were measured. In the second experimental part, the rats’ mean arterial pressure (MAP), heart rate (HR), blood gas levels and other indicators were dynamically monitored in baseline, haemorrhagic shock (HS), at 0point resuscitation (RS 0h) and after 1 h resuscitation (RS 1h). The concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by ELISA kits in both groups of rats at RS 1h. Changes in pathological sections were examined by haematoxylin-eosin (HE) staining. Nuclear factor erythroid 2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1) levels were detected by immunohistochemical analysis, while myeloperoxidase (MPO) levels were detected by immunofluorescence. DHE staining was used to determine reactive oxygen species (ROS) levels. Results The 72h survival rates of the polyHb and polyCOHb groups were 50.00% (6/12) and 58.33% (7/12) respectively, which were significantly higher than that of the 8.33% (1/12) in the HES group (p < 0.05). At RS 0h and RS 1h, the HbCO content of rats in the polyCOHb group (1.90 ± 0.21, 0.80 ± 0.21) g/L were higher than those in the polyHb group (0.40 ± 0.09, 0.50 ± 0.12)g/L (p < 0.05); At RS 1h, the MDA (41.47 ± 3.89 vs 34.17 ± 3.87 nmol/ml) in the plasma, Nrf2 and HO-1 content in the colon of rats in the polyCOHb group were lower than the polyHb group. And the SOD in the plasma (605.01 ± 24.46 vs 678.64 ± 36.37) U/mg and colon (115.72 ± 21.17 vs 156.70 ± 21.34) U/mg and the MPO content in the colon in the polyCOHb group were higher than the polyHb group (p < 0.05). Conclusions In these haemorrhagic shock/resuscitation models, both polyCOHb and polyHb show similar therapeutic effects, and polyCOHb has more effective effects in maintaining MAP, correcting acidosis, reducing inflammatory responses than that in polyHb.

Effect of Oridonin on Experimental Animal Model of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a serious disease that occurs in premature and low-birth-weight infants. In recent years, the incidence of BPD has not decreased, and there is no effective treatment for it. Oridonin (Ori)is a traditional Chinese medicine with a wide range of biological activities, especially pharmacological and anti-inflammatory. It is well known that inflammation plays a key role in BPD. However, the therapeutic effect of Ori on BPD has not been studied. Therefore, in the present study, we will observe the anti-inflammatory activity of Ori in an experimental animal model of BPD. Here, we showed that Ori could significantly decrease hyperoxia-induced alveolar injury, inhibit neutrophil recruitment, myeloperoxidase concentrations, and release inflammatory factors in BPD neonatal rats. Taken together, the experimental results suggested that Ori can significantly improve BPD in neonatal rats by inhibiting inflammatory response.

Effects of postbiotic products from Saccharomyces cerevisiae fermentation on lactation performance, antioxidant capacities, and blood immunity in transition dairy cows

This study aimed to evaluate the effects of dietary supplementation with different types of Saccharomyces cerevisiae fermentation products (SCFP) on lactational performance, metabolism, acute phase protein response, and antioxidant capacities in dairy cows from -21 to 56 d in milk (DIM). One hundred and 80 multiparous Holstein dairy cows were blocked by parity, expected calving date, pre-trial body condition score, and previous 305-d ME yield, and then randomly assigned to 1 of 3 dietary treatments: basal diet (CON; n = 60), basal diet supplemented with 40 g/d of SCFP1 (XPC; n = 60; XPC, Diamond V, Cedar Rapids, IA), and basal diet supplemented with 19 g/d of SCFP2 (NTK; n = 60, NutriTek®, Diamond V, Cedar Rapids, IA). Blood (n = 15, 13 and 12 in the CON, XPC and NTK groups, respectively) was sampled at -7 ± 3, + 3, + 7, + 21, and + 28 d, and milk samples (n = 19, 18 and 15 in the CON, XPC and NTK groups, respectively) was sampled during 1-8 wk from a subset of cows from -21 to 56 d relative to calving. Data were analyzed using the MIXED procedure in SAS (SAS Institute Inc.). All data were subjected to repeated measures ANOVA. Dietary treatment (TRT), time, and their interaction (TRT × time) were considered as fixed effects and cow as the random effect. Cows fed XPC and NTK had greater energy-corrected milk (ECM). Supplementing NTK increased milk fat content and yield, and 3.5% fat-corrected milk (FCM) yield compared with CON. Milk urea nitrogen (MUN) was lower in XPC cows than CON. SCFP supplementation decreased plasma β-hydroxybutyrate (BHB), ceruloplasmin (CER), haptoglobin (HPT), and interleukin-1β (IL-1β) concentrations, whereas increased plasma phosphorus (P) concentrations. In addition, cows fed NTK showed lower creatinine (CR) and cortisol (COR) concentrations but increased plasma calcium (Ca) and myeloperoxidase (MPO) concentrations than those in the CON cows. In addition, cows fed NTK and XPC both had reduced plasma concentrations of serum amyloid-A (SAA) at 3 DIM of lactation compared with CON fed cows. Furthermore, SCFP cows had greater concentrations of plasma glucose (GLU) and calcium (Ca) than CON cows at 7 DIM, and greater concentrations of plasma phosphorus (P) at 21 DIM. Between different SCFP type fed groups, plasma concentrations of nonesterified fatty acids (NEFA), MDA, creatinine (CR), SAA, and HPT were lower in cows fed NTK compared with cows fed XPC at 7 DIM. Overall, our results indicate the potential benefits of supplementing SCFP in transition dairy cows by modulating immunity, liver metabolic function and supporting ECM yield. The results also suggest that NutriTek at 19 g/d appears to support the performance and health of dairy cows better compared with XPC at 40 g/d, based on improved metabolic and inflammatory status during the transition period.