IL-1beta Research Articles

Sildenafil and furosemide nanoparticles as a novel pharmacological treatment for acute renal failure in rats.

Hospitalized patients often develop acute renal failure (ARF), which causes severe morbidity and death. This research investigates the potential renoprotective benefits of sildenafil and furosemide in glycerol-induced ARF, and measures kidney function metrics in response to nanoparticle versions of these medications. Inducing ARF is commonly done by injecting 50% glycerol intramuscularly. Rats underwent a 24-h period of dehydration and starvation before slaughter for renal function testing. We investigated urine analysis, markers of oxidative stress, histology of kidney tissue, immunohistochemistry analysis of caspase-3 and interleukin-1 beta (IL-1 β), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), which are specific indicators of kidney tissue damage. The results of our study showed that the combination of sildenafil and furosemide, using both traditional and nanoparticle formulations, had a greater protective effect on the kidneys compared to using either drug alone. The recovery of renal tissue indicators, serum markers, and urine markers, which are indicative of organ damage, provides evidence of improvement. This was also indicated by the reduction in KIM-1 and NGAL tubular expression. The immunohistochemistry tests showed that the combination therapy, especially with the nanoforms, greatly improved the damaged cellular changes in the kidneys, as shown by higher levels of caspase-3 and IL-1β. According to the findings, a glycerol-induced rat model demonstrates that sildenafil and furosemide, either alone or in combination, in conventional or nanoparticulate forms, improve ARF dysfunction. The synergistic nanoparticulate compositions show remarkable effectiveness. This observation highlights the possible therapeutic implications for ARF treatment.

Nerve Bundle Density and Expression of NGF and IL-1β Are Intra-Individually Heterogenous in Subtypes of Endometriosis

Endometriosis is a gynecological disorder associated with local inflammation and neuroproliferation. Increased nerve bundle density has been attributed to increased expression of nerve growth factor (NGF) and interleukin–1β (IL-1β). Immunohistochemical analysis was carried out on 12 patients presenting with all three anatomic subtypes of endometriosis (deep, superficial peritoneal, endometrioma) at surgery, with at least two surgically excised subtypes available for analysis. Immunolocalization for nerve bundle density around endometriosis using protein gene product 9.5 (PGP9.5), as well as NGF and IL-1β histoscores in endometriosis epithelium/stroma, was performed to evaluate differences in scores between lesions and anatomic subtypes per patient. Intra-individual heterogeneity in scores across lesions was assessed using the coefficient of variation (CV). The degree of score variability between subtypes was evaluated using the percentage difference between mean scores from one subtype to another subtype for each marker. PGP9.5 nerve bundle density was heterogenous across multiple subtypes of endometriosis, ranging from 50.0% to 173.2%, where most patients (8/12) showed CV ≥ 100%. The percentage difference in scores showed that PGP9.5 nerve bundle density and NGF and IL-1β expression were heterogenous between anatomic subtypes within the same patient. Based on these observations of intra-individual heterogeneity, we conclude that markers of neuroproliferation in endometriosis should be stratified by anatomic subtype in future studies of clinical correlation.

Characteristics and Risk Factors for Pediatric Sepsis.

Sepsis is considered a major cause of health loss in children and had high mortality and morbidity. Currently, there is no reliable model for predicting the prognosis of pediatric patients with sepsis. This study aimed to analyze the clinical characteristics of sepsis in children and assess the risk factors associated with poor prognosis in pediatric sepsis patients to identify timely interventions and improve their outcomes. This study analyzed the clinical indicators and laboratory results of septic patients hospitalized in the Pediatric Intensive Care Unit of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, from January 1, 2019, to December 31, 2021. Risk factors for sepsis were identified by logistic regression analyses. A total of 355 children with sepsis were enrolled, with 333 children (93.8%) in the good prognosis group, and 22 children (6.2%) in the poor prognosis group. Among them, there were 255 patients (71.8%) in the sepsis group, and 100 patients (28.2%) in the severe sepsis group. The length of hospital stay in the poor prognosis group was longer than that in the good prognosis group (P<0.01). The levels of interleukin 1β (IL-1β) in the poor prognosis group were higher than those in the good prognosis group (P>0.05), and the platelet (PLT), albumin (ALB), and hemoglobin (Hb) levels were lower in the poor prognosis group (P<0.01). The IL-8 levels in the severe sepsis group were higher than those in the sepsis group (P<0.05). Multiple logistic regression analysis suggested that lower Hb levels, ALB levels, peak PLT counts, and higher IL-1β levels were independent risk factors for poor prognosis in children with sepsis. Lower Hb, ALB, and PLT counts and elevated IL-1β are independent risk factors for poor prognosis in children with sepsis.

Salivary interleukin-17A and interleukin-18 levels in patients with celiac disease and periodontitis

Background An increased level of interleukin-17A and interleukin-18 in the serum and intestinal mucosa of celiac disease patients reflecting the severity of villous atrophy and inflammation was documented. Thus, the objective of this study was to evaluate the concentrations of salivary-17A, interleukin-1 beta, and interleukin-18 in patients with celiac disease who are on a gluten-free diet, both with and without periodontitis, and to compare these levels with those in healthy individuals. Methods The study involved 23 participants with serologically confirmed celiac disease (CD) and 23 control subjects. The CD patients had been following a gluten-free diet (GFD) for a minimum of 1 year and had no other autoimmune disorders. The research involved collecting demographic data, conducting periodontal examinations, gathering unstimulated whole saliva, and performing enzyme-linked immunosorbent assays to measure salivary interleukin-17A, interleukin-1 beta, and interleukin-18 levels. Spearman’s correlation analysis was utilized to explore the relationships between CD markers in patients on a GFD and their periodontal clinical findings. Results The periodontal findings indicated significantly lower values in celiac disease patients adhering to a gluten-free diet compared to control subjects (p = 0.001). No significant differences were found in salivary IL-17A, IL-18, and IL-1B levels between celiac disease patients and control subjects. Nevertheless, the levels of all interleukins were elevated in periodontitis patients in both the celiac and control groups. The IL-1 Beta level was significantly higher in periodontitis patients compared to non-periodontitis patients in the control group (p = 0.035). Significant negative correlations were observed between serum IgA levels and plaque index (r = −0.460, p = 0.010), as well as gingival index (r = −0.396, p = 0.030) in CD patients on a gluten-free diet. Conclusion Celiac disease patients on gluten-free diet exhibited better periodontal health compared to control subjects. However, increased levels of salivary IL-17A, IL-18 and IL-1B levels were associated with periodontitis. Additionally, serum IgA level was significantly inversely associated with periodontitis clinical manifestations and with salivary inflammatory mediators in CD patients on GFD.

Lipopolysaccharide Stimulation of Peripheral Blood Mononuclear Cells of Indigenous Pigs Causes Enhanced Expression of Pro-inflammatory Cytokines Over Exotic Pigs

Background: Selective breeding in pigs based on a higher potential of disease resistance can be achieved by studying the association between immune responsiveness and susceptibility to infectious diseases. The early immune responsiveness of pigs assessed in a quantifiable scale for different determinant cytokine genes’ expression involved in regulation of immune response can be a major determinant for evaluating the immune responsiveness. Methods: In this study, we carried out the quantitative relative expression of candidate cytokine genes [Interleukin-1 beta-(IL1b), IL6, IL10 and tumor necrosis factor-alpha (TNFa) and toll-like receptor-4 (TLR4) gene expression in the lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMCs) of Zovawk (indigenous) and Large White Yorkshire (LWY-exotic) pig breeds using real-time PCR to understand the differences in swift immune responsiveness against gram-negative bacteria. Results: Zovawk PBMCs’ pro-inflammatory cytokines IL1b and IL6 expression increased rapidly with LPS stimulation up to 12 h, being significantly higher as early as 4 h compared to that of the LWY PBMCs. In Zovawk pigs, the pro-inflammatory cytokine genes’ expression was found to be quick and high; whereas, in LWY pigs the response was slow and low. Interestingly, the expression of IL10 was not detected in LPS-stimulated PBMCs of Zovawk pigs indicating that the remarkably higher expressions of IL6 and IL1b in response to LPS are within the threshold of the Zovawk pigs which have evolved through generations. Our findings clearly indicate the sturdy and early immune responsiveness of indigenous pigs against gram-negative bacteria over the exotic pigs.

Stryphnodendron adstringens have a modulatory effect on inflammatory cytokines markers of in vitro activated macrophages

Aim: The purpose of this study is to conduct a comprehensive investigation into the modulatory effects of Stryphnodendron adstringens (Mart.; S. adstringens), a Brazilian wound-healing plant, on the expression of inflammatory cytokines. This will be achieved using an in vitro protocol with the commercial macrophage cell line RAW 264.7. Methods: The macrophage inflammatory response was induced by the natural antigen phytohemagglutinin (PHA), with and without supplementation of different concentrations of S. adstringens extract. The effects on cell proliferation rate and the concentration and production of transcripts of pro-inflammatory cytokines interleukin 1β (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), as well as the anti-inflammatory cytokine IL-10, were assessed using spectrophotometric, immunoassay, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) techniques. Results: S. adstringens extract at all concentrations tested here reduced the cellular proliferation rate of activated macrophages. Extracts at concentrations of 0.49 mg/mL and 0.99 mg/mL decreased the protein and gene expression of pro-inflammatory cytokines, exhibiting the opposite effect concerning IL-10. Conclusions: The findings suggest that the wound-healing action of S. adstringens may encompass differential modulation of inflammation associated with tissue injury.

The impact of sericin on inflammation, oxidative stress, and lipid metabolism in female rats with experimental knee osteoarthritis.

This study investigated the effects of sericin on inflammation, oxidative stress, and lipid metabolism in female rats with experimental knee osteoarthritis (KOA), focusing on evaluating its effectiveness via the sterol regulatory protein (SREBP)-1C and SREBP-2 pathways. The rats were randomly assigned to three experimental groups: the C group (control), the KOA group (KOA control), and the sericin group (KOA + sericin). The KOA model was created by injecting monosodium iodoacetate (MIA) into the knee joint. Sericin was administered intra-articularly to rats on days 1, 7, 14, and 21 (0.8g/kg/mL, 50 µL). After 21days, the rats were sacrificed, and serum samples were analyzed using an ELISA to measure tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-10, SREBP-1c, SREBP-2, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), cholesterol, triglyceride, and total oxidant-antioxidant status (TOS-TAS) levels. The KOA group exhibited higher serum TNF-α, IL-1β, TOS, SREBP-1C, ACC, FAS, triglyceride, SREBP-2, and cholesterol levels than the C group (P < 0.05). However, the levels of these cytokines, except cholesterol, were significantly lower in the sericin group than in the KOA group. The KOA group exhibited significantly lower serum TAS and IL-10 levels than the C group (P < 0.05). In the sericin group, there was a statistically significant increase (P < 0.05). Sericin shows promising potential for reducing inflammation, oxidative stress, and lipid metabolism in experimental models of KOA in rats. However, further clinical research is necessary to validate the potential of sericin as a therapeutic agent for treating KOA. Key Points • Sericin can reduce knee osteoarthritis (KOA) symptoms in an experimental rat model. • In particular, in the serum of an experimental KOA rat model, sericin specifically reduces the levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), and increases the levels of anti-inflammatory cytokines, such as IL-10. • Sericin reduced lipid metabolism via the sterol regulatory protein (SREBP)-1C and SREBP-2 pathways and oxidative stress in the serum of the experimental KOA rat model. • The intra-articular administration of sericin has been shown to significantly reduce lipid metabolism, oxidative stress, and inflammation, as supported by biochemical analysis. These findings suggest its promising potential as an alternative treatment option for KOA.

Polystyrene nanoplastics mediate oxidative stress, senescence, and apoptosis in a human alveolar epithelial cell line

BackgroundNanoplastics, an emerging form of pollution, are easily consumed by organisms and pose a significant threat to biological functions due to their size, expansive surface area, and potent ability to penetrate biological systems. Recent findings indicate an increasing presence of airborne nanoplastics in atmospheric samples, such as polystyrene (PS), raising concerns about potential risks to the human respiratory system.MethodsThis study investigates the impact of 800 nm diameter-PS nanoparticles (PS-NPs) on A549, a human lung adenocarcinoma cell line, examining cell viability, redox balance, senescence, apoptosis, and internalization. We also analyzed the expression of hallmark genes of these processes.ResultsWe demonstrated that PS-NPs of 800 nm in diameter significantly affected cell viability, inducing oxidative stress, cellular senescence, and apoptosis. PS-NPs also penetrated the cytoplasm of A549 cells. These nanoparticles triggered the transcription of genes comprised in the antioxidant network [SOD1 (protein name: superoxide dismutase 1, soluble), SOD2 (protein name: superoxide dismutase 2, mitochondrial), CAT (protein name: catalase), Gpx1 (protein name: glutathione peroxidase 1), and HMOX1 (protein name: heme oxygenase 1)], senescence-associated secretory phenotype [Cdkn1a (protein name: cyclin-dependent kinase inhibitor 1A), IL1A (protein name: interleukin 1 alpha), IL1B (protein name: interleukin 1 beta), IL6 (protein name: interleukin 6), and CXCL8 (protein name: C-X-C motif chemokine ligand 8)], and others involved in the apoptosis modulation [BAX (protein name: Bcl2 associated X, apoptosis regulator), CASP3 (protein name: caspase 3), and BCL2 (protein name: Bcl2, apoptosis regulator)].ConclusionCollectively, this investigation underscores the importance of concentration (dose-dependent effect) and exposure duration as pivotal factors in assessing the toxic effects of PS-NPs on alveolar epithelial cells. Greater attention needs to be directed toward comprehending the risks of cancer development associated with air pollution and the ensuing environmental toxicological impacts on humans and other terrestrial mammals.

Protective Role of MerTK in Diabetic Peripheral Neuropathy via Inhibition of the NF-κB Signaling Pathway.

Diabetic peripheral neuropathy (DPN) impacts patient quality of life. In such patients, increased expression of mer tyrosine kinase (MerTK) has been demonstrated; however, its mechanism of action remains unclear. In this study, type 2 diabetes mellitus (T2DM) and DPN models were established in Sprague Dawley rats via low-dose streptozotocin and a high-fat diet and the mode of action of MerTK was examined. MerTK-specific inhibitors were administered by gavage once daily for 2 weeks. Sciatic nerve conduction velocity and nerve structure were measured. The levels of MerTK, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and relevant biochemical indexes were detected. The study revealed upregulation of MerTK expression in T2DM and more so in DPN groups. Inhibiting MerTK led to reduced nerve conduction velocity and further deterioration of sciatic nerve structure, as evidenced by structural morphology. Concurrently, serum levels of total cholesterol, glycated hemoglobin, and triglyceride significantly increased. Moreover, levels of NF-κB increased in both serum and nerve tissue, alongside a significant rise in TNF-α and IL-1β expressions. MerTK could bind to the inhibitor of kappa B kinase beta (Ikbkb) in Schwann cells, establishing Ikbkb as a precursor to NF-κB activation. Inhibition of MerTK exacerbates neuropathy, indicating its protective role in DPN by suppressing the NF-κB pathway, highlighting a potential new target for its diagnosis and treatment.

Hepatoprotective effects of baicalein against liver ischemia-reperfusion injury and partial hepatectomy in a rat model.

Baicalein is the main active flavonoid in Scutellariae Radix and is included in shosaikoto, a Kampo formula used for treating hepatitis and jaundice. However, little is known about its hepatoprotective effects against hepatic ischemia-reperfusion injury (HIRI), a severe clinical condition directly caused by interventional procedures. We aimed to investigate the hepatoprotective effects of baicalein against HIRI and partial hepatectomy (HIRI + PH) and its potential underlying mechanisms. Male Sprague-Dawley rats received either baicalein (5mg/kg) or saline intraperitoneally and underwent a 70% hepatectomy 15min after hepatic ischemia. After reperfusion, liver and blood samples were collected. Survival was monitored 30min after hepatic ischemia and hepatectomy. In interleukin 1β (IL-1β)-treated primary cultured rat hepatocytes, the influence of baicalein on inflammatory mediator production and the associated signaling pathway was analyzed. Baicalein suppressed apoptosis and neutrophil infiltration, which are the features of HIRI + PH treatment-induced histological injury. Baicalein also reduced the mRNA expression of the proinflammatory cytokine tumor necrosis factor-α (TNF-α). In addition, HIRI + PH treatment induced liver enzyme deviations in the serum and hypertrophy of the remnant liver, which were suppressed by baicalein. In the lethal HIRI + PH treatment group, baicalein significantly reduced mortality. In IL-1β-treated rat hepatocytes, baicalein suppressed TNF-α and chemokine mRNA expression as well as the activation of nuclear factor-kappa B (NF-κB) and Akt. Baicalein treatment attenuates HIRI + PH-induced liver injury and may promote survival. This potential hepatoprotection may be partly related to suppressing inflammatory gene induction through the inhibition of NF-κB activity and Akt signaling in hepatocytes.

NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation.

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic β-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor β1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1β), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.

Chlorella vulgaris algae ameliorates chlorpyrifos toxicity in Nile tilapia with special reference to antioxidant enzymes and Streptococcus agalactiae infection

BackgroundChlorpyrifos (CPF) is a widely used pesticide in the production of plant crops. Despite rapid CPF biodegradation, fish were exposed to wastewater containing detectable residues. Recently, medicinal plants and algae were intensively used in aquaculture to replace antibiotics and ameliorate stress impacts.Methods and resultsAn indoor experiment was conducted to evaluate the deleterious impacts of CPF pollution on Nile tilapia health and the potential mitigation role of Chlorella vulgaris algae. Firstly, the median lethal concentration LC50 − 72 h of CPF was determined to be 85.8 µg /L in Nile tilapia (35.6 ± 0.5 g body weight) at a water temperature of 27.5 °C. Secondly, fish were exposed to 10% of LC50 − 72 h for six weeks, and tissue samples were collected and examined every two weeks. Also, Nile tilapia were experimentally infected with Streptococcus agalactiae. Exposed fish were immunosuppressed expressed with a decrease in gene expressions of interleukin (IL) 1β, IL-10, and tumor necrosis factor (TNF)-α. Also, a decline was recorded in glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) gene expression in the head kidney tissue. A high mortality rate (MR) of 100% was recorded in fish exposed to CPF for six weeks and challenged with S. agalactiae. Fish that received dietary C. vulgaris could restore gene expression cytokines and antioxidants compared to the control. After six weeks of CPF exposure, fish suffered from anemia as red blood cell count (RBCs), hemoglobin (Hb), and packed cell volume (PCV) significantly declined along with downregulation of serum total protein (TP), globulin (GLO), and albumin (ALB). Liver enzymes were significantly upregulated in fish exposed to CPF pollution, alanine aminotransferase (ALT) (42.5, 53.3, and 61.7 IU/L) and aspartate aminotransferase (AST) (30.1, 31.2, and 22.8) after 2, 4, and 6 weeks, respectively. On S. agalactiae challenge, high MR was recorded in Nile tilapia exposed to CPF (G3) 60%, 60%, and 100% in week 2, week 4, and week 6, and C. vulgaris provided a relative protection level (RPL) of 0, 14.29, and 20%, respectively.ConclusionsIt was concluded that CPF pollution induces immunosuppressed status, oxidative stress, and anemic signs in Nile tilapia. In contrast, C. vulgaris at a 50 g/kg fish feed dose could partially ameliorate such withdrawals, restoring normal physiological parameters.

Influence of administration timing of San-Huang-Xie-Xin-Tang treatment on attenuating Salmonella enterica serovar Typhimurium infection.

Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1β levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.

Utilizing outer membrane proteins (OMPs) as a vaccine to manage motile Aeromonas septicemia (MAS) in Nile tilapia (Oreochromis niloticus) with evaluating the vaccine immunoprotective effectiveness

AbstractMotile aeromonads are an opportunistic and heterogenic bacteria that cause motile Aeromonas septicemia (MAS) which is accompanied with variety of clinical signs and lesions in fish. It has been found that their outer membrane proteins (OMPs) are highly immunogenic and may be used as a vaccine candidate. The present study was undertaken to evaluate OMP protection against Aeromonas hydrophila (A. hydrophila) strain ATCC 7966 (A5 and A8) and A. hydrophila strain DSM 30,187 (A6). Pathogenicity tests revealed that out of 12 isolated strains, seven were highly pathogenic, three were moderate, and two were avirulent. SDS-PAGE analysis of OMPs showed several protein bands (7–22) of different molecular weights ranging from 14 to 346 kDa. The common protein band was 39 kDa. It seems that pathogenicity and the number of protein bands are related in the highly pathogenic strains. Challenged A. hydrophila for Nile tilapia (O. niloticus) previously actively immunized with OMPs (A4, A5, A6, A8, and A11) showed a significant increase in relative percent survival (RPS) ranging from 50 to 100%. Immunological parameters such as immunoglobulin M (IgM), antioxidants (SOD, GSH, and CAT), and nitric oxide (NO) and expression of pro-inflammatory cytokines, interleukin 1β (IL-1β), and tumor necrosis factor-α (TNFα) showed a significant increase in OMP-immunized fish. Challenged A. hydrophila for O. niloticus previously passively immunized with OMPs (A4, A5, A6, A8, and A11) in fish-raised sera showed a significant increase in RPS (20 to 100%) in the vaccinated groups. It is concluded that OMPs from Aeromonas spp. have been identified as suitable target for protection development, especially in the case of heterogenic bacteria.

Asiatic acid rescues intestinal tissue by suppressing molecular, biochemical, and histopathological changes associated with the development of ulcerative colitis.

Asiatic acid (AA) is a polyphenolic compound with potent antioxidative and anti-inflammatory activities that make it a potential choice to attenuate inflammation and oxidative insults associated with ulcerative colitis (UC). Hence, the present study aimed to evaluate if AA can attenuate molecular, biochemical, and histological alterations in the acetic acid-induced UC model in rats. To perform the study, five groups were applied, including the control, acetic acid-induced UC, UC-treated with 40 mg/kg aminosalicylate (5-ASA), UC-treated with 20 mg/kg AA, and UC-treated with 40 mg/kg AA. Levels of different markers of inflammation, oxidative stress, and apoptosis were studied along with histological approaches. The induction of UC increased the levels of lipid peroxidation (LPO) and nitric oxide (NO). Additionally, the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant proteins [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR)] were downregulated in the colon tissue. Moreover, the inflammatory mediators [myeloperoxidase (MPO), monocyte chemotactic protein 1 (MCP1), prostaglandin E2 (PGE2), nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β)] were increased in the colon tissue after the induction of UC. Notably, an apoptotic response was developed, as demonstrated by the increased caspase-3 and Bax and decreased Bcl2. Interestingly, AA administration at both doses lessened the molecular, biochemical, and histopathological changes following the induction in the colon tissue of UC. In conclusion, AA could improve the antioxidative status and attenuate the inflammatory and apoptotic challenges associated with UC.

Immunomodulatory effects of Stevia rebaudiana leaves and commercial stevia on rats: a comparative study

Stevia is herbal native to South-America that is renowned for its natural sweet leaves containing stevia glycosides. Our study aimed at examining and comparing the immunomodulatory effects of the Stevia rebaudiana leaf extract and of commercially-available stevia products in rats. Our experiment involved the preparation of Stevia rebaudiana leaf extract and the use of market-available stevia obtained from the local-market. Stevia rebaudiana leaf extraction was meticulously performed, and 60 healthy adult male rats were randomly separated into three groups: untreated control, commercial stevia treatment (25 mg/kg), and Stevia rebaudiana leaf extract treatment (25 mg/kg). The rats were orally administered the treatments for 60 days, after which blood samples were collected for analysis. Our results revealed a significant rise in interleukin-1 beta (IL-1β) levels in rats treated with the Stevia rebaudiana leaf extract and the commercially-available stevia when compared to the control group. Additionally, immunoglobulin A (IgA) levels exhibited a notable increase in both stevia-treated groups, with the Stevia rebaudiana leaf extract-receiving group showing higher IgA levels than the commercially-available stevia-treated one. Our findings suggest that stevia may influence the immune response, particularly the regulation of the pro-inflammatory cytokine IL-1β and the IgA levels. This study contributes valuable insights into stevia’s effects on the immune system.

Study of some immunological indicators for COVID-19 patients in Babylon city

Study of some immunological indicators for COVID-19 patients in Babylon city

102 Circadian patterns of behavior, respiration, rectal temperature, saliva melatonin, cytokine concentrations, and milk immune cells are altered by cooling heat-stressed lactating sows

Abstract Lactating sows are particularly vulnerable to heat stress (HS) due to the increased metabolism from milk production. A greater understanding of HS response could assist in mitigating its detrimental effects on animal production. Two core circadian clock genes were pinpointed in a recent genome study as potential mediators of HS response, indicating the possible alteration of circadian clocks by HS exposure. This study aimed to assess how cooling of lactating sows under natural heat stress conditions in the summer influenced circadian patterns of respiration rate (RR), rectal temperature (RT), behaviors, salivary concentration of cortisol and melatonin, milk cell populations and relative abundance of multiple cytokines in saliva. Lactating sows of mixed parities were divided into two treatment groups: treated with electronic cooling pad (C; n=9) and heat-stressed control (H; n=9). Experiments were conducted during two 48 h periods of increased environmental temperatures from summer heatwaves. During the initial 48 h period, rectal temperature (RT) was monitored every 60 min, rectal temperature (RT) every 30 min, and behaviors of eating, standing, sitting, laying, sleeping, drinking, and nursing every 5 min. Morning milk samples were collected following the completion of the first phase and utilized to categorize and count somatic cells. The second trial was approximately 1 wk later, and during this period saliva samples were collected every 4 h over the 48-h period. Results were analyzed for significant effect of treatments and interaction using periodic regression while circadian patterns were further detected by incorporating a Fourier series model utilizing sine-cosine variables that denote a fit and/or shift in circadian pattern. The analysis revealed that cooling decreased RT and RR while also modifying circadian patterns (P &amp;lt; 0.05). Cooling had no impact on the percentage of time spent in any activity over the 48-h period (P &amp;gt; 0.05). Nevertheless, the daily patterns of eating, standing, and sitting were different between the treatments (P &amp;lt; 0.05). A shift in eating time to later in the day in H sows relative to C sows related to a second rise in RT during the dark phase of the light-dark cycle (P &amp;lt; 0.05). Saliva melatonin concentrations were increased in C sows and circadian pattern altered relative to H (P &amp;lt; 0.05), but there was no effect on salivary cortisol concentrations (P &amp;gt; 0.05). Cooling reduced milk lymphocytes (P &amp;lt; 0.05) and influenced diurnal pattern of saliva cytokines including interleukins (IL) IL-1 alpha, IL-1 beta, IL-10, and IL-15 and transforming growth factor-beta 1. In conclusion, the cooling of heat-stressed sows altered the circadian patterns of physiology, behavior and melatonin, suggesting the need for additional research to investigate whether circadian disruption contributes to reduced production efficiency observed in HS animals.

Parthenolide alleviates indomethacin-induced gastric ulcer in rats via antioxidant, anti-inflammatory, and antiapoptotic activities.

Parthenolide (PTL) is a sesquiterpene lactone that occurs naturally. It demonstrates a variety of beneficial effects, such as antioxidant, anti-inflammatory, and antiapoptotic properties. The study investigated the potential protective impact of PTL on indomethacin (INDO) induced stomach ulcers in rats. The rats were classified into 5 distinct categories. Group 1 served as the "control" group. Rats in the second group received a single oral dosage of INDO (50 mg kg-1). Rats inGroups three and four received 20 and 40 mg kg-1 oral PTL 1 h before INDO. Omeprazole (30mgkg-1) was given orally to Group 5 rats 1h before INDO. Pretreatment with PTL increased stomach pH and decreased gastric volume as well as reduced the morphological and histological changes induced by INDO. Analysis of probable pathways showed that pre-treatment with PTL successfully reduced oxidative, inflammatory, and apoptotic consequences caused by INDO. The ingestion of PTL leads to a notable increase in the levels of glutathione reduced (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT). Furthermore, PTL decreased the concentration of malondialdehyde (MDA). In contrast, it was shown that PTL increased both cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2). PTL shows a significant decrease in the expression of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB). PTL therapy resulted in a decrease in Bcl-2-associated X protein (Bax) levels and an increase in B-cell lymphoma 2 (Bcl2) levels. In conclusion, PTL offers gastroprotection by its antioxidant, anti-inflammatory, and anti-apoptotic qualities.

Bioinformatics analysis of hypoxia associated genes and inflammatory cytokine profiling in COPD-PH

Pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is associated with worse clinical outcomes and decreased survival rates. In absence of disease specific diagnostic/therapeutic targets and unclear pathophysiology, there is an urgent need for the identification of potential genetic/molecular markers and disease associated pathways. The present study aims to use a bioinformatics approach to identify and validate hypoxia-associated gene signatures in COPD-PH patients. Additionally, hypoxia-related inflammatory profile is also explored in these patients.Microarray dataset obtained from the Gene Expression Omnibus repository was used to identify differentially expressed genes (DEGs) in a hypoxic PH mice model. The top three hub genes identified were further validated in COPD-PH patients, with chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL12 showing significant changes in comparison to healthy controls. Furthermore, multiplexed analysis of 10 inflammatory cytokines, tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF-β), interleukin 1-beta (IL-1β), IL-4, IL-5, IL-6, IL-13, IL-17, IL-18 and IL-21 was also performed. These markers showed significant changes in COPD-PH patients as compared to controls. They also exhibited the ability to differentially diagnose COPD-PH patients in comparison to COPD. Additionally, IL-6 and IL-17 showed significant positive correlation with systolic pulmonary artery pressure (sPAP).This study is the first report to assess the levels of CXCL9 and CXCL12 in COPD-PH patients and also explores their link with the inflammatory profile of these patients. Our findings could be extended to better understand the underlying disease mechanism and possibly used for tailoring therapies exclusive for the disease.