Tumor Necrosis Factor-α Concentrations Research Articles

Acute Hormonal and Inflammatory Responses following Lower and Upper Body Resistance Exercises Performed to Volitional Failure.

This study aimed to investigate the effects of a single bench press (BP) vs. leg press (LP) resistance training sessions on testosterone, cortisol, C-reactive protein (CRP) interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) concentrations, and creatine kinase (CK) activity in strength-trained males. Eleven strength-trained males participated in a cross-over randomized trial, undergoing two experimental sessions each consisting of five sets of the BP or the LP exercise to volitional failure with a load corresponding to 50% of one-repetition maximum. Blood samples were taken at baseline (BA), immediately post (POST), and 1 h after the cessation of exercise (POST-1). A significant increase in IL-6 concentration from BA to POST-1 was observed during the LP condition (p = 0.004; effect size [ES] = 0.64). Additionally, a significant main effect of time was found for increasing testosterone concentrations from BA to POST exercise (p = 0.014; ES = 0.25). A significantly lower cortisol concentration at POST-1 compared to POST (p = 0.001; ES = 1.02) was noted in the BP condition. Furthermore, a significantly lower cortisol concentration was found at POST-1 in the BP compared to the LP condition (p = 0.022; ES = 1.3). A significant increase in CK activity was reported from BA to POST (p = 0.024; ES = 0.69) and POST-1 (p = 0.045; ES = 0.55) during the LP condition, and from BA to POST-1 (p = 0.014; ES = 0.96) during the BP condition. No significant differences were found in the CRP (p = 0.659) and TNF-α concentrations (p = 0.487). These results suggest that the amount of muscle mass engaged during the resistance exercise may influence the changes in IL-6 and cortisol concentrations. Larger muscle groups, as engaged in the LP, more likely lead to elevated concentrations of IL-6 myokine.

Oral administration of liposome-encapsulated thymol could alleviate the inflammatory parameters in serum and hippocampus in a rat model of Alzheimer's disease

BackgroundNeuroinflammation is closely related to Alzheimer's Disease (AD) pathology, hence supplements with anti-inflammatory property could help attenuate the progression of AD. This study was conducted to evaluate the potential anti-inflammatory effects of liposome encapsulated thymol (LET), administered orally, in prevention of Alzheimer in a rat model by anti-inflammatory mechanisms. MethodsThe rats were grouped into six groups (n = 10 animals per group), including Control healthy (Con), Alzheimer's disease (AD) model, AD model treated with free thymol in 40 and 80 mg/kg body weight (TH40 and TH80), AD model treated with LET in 40 and 80 mg/kg of body weight (LET40 and LET80). The behavioral response of step through latency (Passive Avoidance Test), concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) were assessed in serum and hippocampus. ResultsThe results showed that significant increase in concentrations of IL-1β (P = 0.001), IL-6 (P = 0.001), TNF-α (P = 0.001) and COX-2 (P = 0.001) in AD group compared with healthy control rats. AD induction significantly reduced step through latency and revealed deficits in passive avoidance performance. The results also showed the treatment with free thymol especially in higher concentrations and also LTE could decrease serum concentrations of IL-1β (P < 0.05), IL-6 (P < 0.05), TNF-α (P < 0.05), and COX-2 (P < 0.05) and increase BDNF (P < 0.05) compared with control Alzheimer rats in hippocampus and serum. There were also significant correlations between serum and hippocampus concentrations of IL-1β (r2 = 0.369, P = 0.001), IL-6 (r2 = 0.386, P = 0.001), TNF-α (r2 = 0.412, P = 0.001), and COX-2 (r2 = 0.357, P = 0.001). It means a closed and positive relation between serum and hippocampus concentrations of IL-1β, IL-6, TNF-α, and COX-2. ConclusionsLET demonstrates its ability to attenuate neuroinflammatory reaction in AD model through suppression of IL-1β, IL-6, and TNF-α and COX-2 indicators. Hence, it can ameliorate AD pathogenesis by declining inflammatory reaction.

Effects of Dietary Callicarpa nudiflora Aqueous Extract Supplementation on Growth Performance, Growth Hormone, Antioxidant and Immune Function, and Intestinal Health of Broilers.

C. nudiflora is notably rich in flavonoids and phenylethanoid glycosides, making it a significant natural source of antioxidants. We examined the effects of C. nudiflora aqueous extract (CNE) on growth performance, antioxidant function, immunity, intestinal barrier function, nutrient transporters, and microbiota of broilers. A total of 360 one-day-old broilers were randomly assigned to four treatment groups: a basal diet with 0 (control, CON), 300 mg/kg (CNEL), 500 mg/kg (CNEM), and 700 mg/kg (CNEH) CNE for 42 days. CNEL and CNEM groups quadratically increased body weight and average daily gain but decreased feed-to-gain ratios during the starter and whole phases. Regarding the immune response of broilers, CNE treatment linearly down-regulated jejunal myeloid differentiation factor 88 (MyD88) expression and interleukin-1β (IL-1β) and interferon-γ expression in the liver (d 21), while decreasing jejunal IL-1β expression and the concentration of serum tumor necrosis factor-α and interleukin-6 (d 42). The CNEM and CNEH groups had lower MyD88 and nuclear factor kappa B expression in the liver (d 21) compared to the CON group. Broilers in the CNEL and CNEM groups had higher spleen index and thymus index (d 21) and interleukin-10 expression from the liver and jejunal mucosa (d 42) than that in the CON group. For the antioxidant capacity of broilers, CNE treatment linearly decreased the content of malonaldehyde and increased the activity of total antioxidant capacity in serum (d 42). CNEM and CNEH groups linearly increased the activity of superoxide dismutase in serum and heme oxygenase-1 expression in the liver, while increasing the activity of glutathione peroxidase in serum, jejunal nuclear factor E2-related factor 2 expression, and NAD(P)H quinone oxidoreductase 1 expression in the liver (d 42). As for the growth hormone of broilers, CNEM group increased the level of serum insulin-like growth factor 1 and up-regulated jejunal glucagon-like peptide 2 (GLP-2) expression (d 21). Broilers in the CNEM and CNEH groups had higher jejunal GLP-2 expression and growth hormone (GH) expression in the liver and the level of serum GH (d 42) than that in the CON group. Additionally, the villus height and jejunal Occludin and Claudin-1 expression in the CNEM group increased. CNE-containing diets resulted in a linear increase in the expression of jejunal zonula occluden-1 (d 21), villus height to crypt depth ratio, jejunal Occludin, excitatory amino acid transporters-3, and peptide-transporter 1 (d 42). The regulation of Oscillospira, Ruminococcaceae_Ruminococcus, and Butyricicoccus genera indicated that CNEH altered the composition of the cecal microbiota. In general, supplementing broilers with C. nudiflora aqueous extract could boost hormones, immune and antioxidant function, and gut health, improving their growth performance. Hence, CNE was a promising poultry feed additive, with 500 mg/kg appearing to be the optimal dose.

Dexmedetomidine Attenuates Inflammation in Elderly Patients Following Major Hepatobiliary and Pancreatic Surgery: A Randomized Clinical Trial.

Dexmedetomidine (Dex) may have anti-inflammatory properties and potentially reduce the incidence of postoperative organ injury. To investigate whether Dex protects pulmonary and renal function via its anti-inflammatory effects in elderly patients undergoing prolonged major hepatobiliary and pancreatic surgery. Between October 2019 and December 2020, this randomized controlled trial was carried out at a tertiary hospital in Chongqing, China. 86 patients aged 60-75 who underwent long-duration (> 4 hrs) hepatobiliary and pancreatic surgery without significant comorbidities were enrolled and randomly assigned into two groups at a 1:1 ratio. Patients were given either Dex or an equivalent volume of 0.9% saline (Placebo) with a loading dose of 1 μg kg-1 for 10 min, followed by 0.5 μg kg-1 hr-1 for maintenance until the end of surgery. The changes in serum concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were primary outcomes. At one hour postoperatively, serum IL-6 displayed a nine-fold increase (P<0.05) in the Placebo group. Administration of Dex decreased IL-6 to 278.09 ± 45.43 pg/mL (95% CI: 187.75 to 368.43) compared to the Placebo group (P=0.019; 432.16 ± 45.43 pg/mL, 95% CI: 341.82 to 522.50). However, no significant differences in TNF-α were observed between the two groups. The incidence of postoperative acute kidney injury was twice as high in the Placebo group (9.30%) compared to the Dex group (4.65%), and the incidence of postoperative acute lung injury was 23.26% in the Dex group, lower than that in the Placebo group (30.23%), although there was no statistical significance between the two groups. Dex administration in elderly patients undergoing major hepatobiliary and pancreatic surgery reduces inflammation and potentially protects kidneys and lungs. Chinese Clinical Trials Registry, identifier: ChiCTR1900024162, on 28 June 2019.

Single administration of a psychedelic [(R)-DOI] influences coping strategies to an escapable social stress

Psychedelic compounds have potentially rapid, long-lasting anxiolytic, antidepressive and anti-inflammatory effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT2A receptor partial agonist, decreases stress-related behavior in male mice exposed to repeated social aggression. Additionally, we explored the likelihood that these behavioral changes are related to anti-inflammatory properties of [(R)-DOI]. Animals were subjected to the Stress Alternatives Model (SAM), an escapable social stress paradigm in which animals develop reactive coping strategies - remaining in the SAM arena (Stay) with a social aggressor, or dynamically initiated stress coping strategies that involve utilizing the escape holes (Escape) to avoid aggression. Mice expressing these behavioral phenotypes display behaviors like those in other social aggression models that separate animals into stress-vulnerable (as for Stay) or stress-resilient (as for Escape) groups, which have been shown to have distinct inflammatory responses to social stress. These results show that Stay animals have heightened cytokine gene expression, and both Stay and Escape mice exhibit plasma and neural concentrations of the inflammatory cytokine tumor necrosis factor-α (TNFα) compared to unstressed control mice. Additionally, these results suggest that a single administration of (R)-DOI to Stay animals in low doses, can increase stress coping strategies such as increasing attention to the escape route, promoting escape behavior, and reducing freezing during socially aggressive interaction in the SAM. Lower single doses of (R)-DOI, in addition to shifting behavior to suggest anxiolytic effects, also concomitantly reduce plasma and limbic brain levels of the inflammatory cytokine TNFα.

Rectal microbiomes and serum metabolomics reveal the improved effect of Artemisia ordosica crude polysaccharides on the lactation performance, antioxidant and immune responses of lactating donkeys

This study is aimed at investigating the effects of dietary supplementation with Artemisia ordosica crude polysaccharides (AOCP) on lactation performance, antioxidant status, and immune status of lactating donkeys and analyzing rectal microbiomes and serum metabolomes. Fourteen lactating Dezhou donkeys with similar age (6.16 ± 0.67 years of BW ± SD), weight (250.06 ± 25.18 kg), days in milk (39.11 ± 7.42 d), and averaged parity of 3 were randomly allocated into 2 treatments: a control group (CON, basal diet) and an AOCP group (AOCP, basal diet with 1.0 g/kg DM AOCP). Ten weeks were allotted for the experiment, 2 weeks for adaptation, and 8 weeks for collecting data and samples. The results showed that supplementation of donkey diets with AOCP increased lactation performance, including dry matter intake, milking yield, estimated milk yield, solids-corrected milk, energy-corrected milk, milk fat yield, milk protein yield, milk lactose yield, milk total solids yield, and milk solid not fat yield. The digestibility of dry matter, crude protein, acid detergent fiber, and neutral detergent fiber was increased in the AOCP group compared with the CON group. The AOCP group increased the concentrations of immunoglobulin A, immunoglobulin G, and immunoglobulin M, the activities of the superoxide dismutase, catalase and total antioxidant capacity in the serum. AOCP decreased the concentrations of tumor necrosis factor-α, nitric oxide, reactive oxygen species, and malondialdehyde in the serum. Compared with the CON group, AOCP increased propionate, butyrate, isovalerate, and total VFA concentrations in rectal feces (P < 0.05). The addition of AOCP to increased diversity (Shannon index) and altered structure of the rectal microflora. As a result of AOCP supplementation, there has been a significant improvement in the colonization of beneficial bacteria, including Lactobacillus, Unclassified_f_Prevotellacea, Ruminococcus, and Fibrobacter genera. In contrast, a decrease in the colonization of the Clostridium_sensu_stricto_1 bacterial genus and other pathogenic bacteria was observed. Meanwhile, metabolomics analysis found that AOCP supplementation upregulated metabolites L-tyrosine content while downregulating 9(S)-HODE, choline, sucrose, LysoPC (18:0), LysoPC (18:1(9Z), and LysoPC (20:2(11Z,14Z)) concentrations. These altered metabolites were involved in the PPAR signaling pathway, prolactin signaling pathway, glycerophospholipid metabolism, carbohydrate digestion and absorption, and tyrosine metabolism pathways, which were mainly related to antioxidant capacity, immune responses, and protein metabolism in the lactating donkeys. As a consequence of feeding AOCP diets, beneficial bacteria were abundant, and antioxidant and protein metabolism-related pathways were enriched, which may enhance lactation performance in donkeys. Therefore, supplementing AOCP diets is a desirable dietary strategy to improve donkey health and lactation performance.

The Influence of Neodymium-Doped Yttrium Aluminum Garnet Laser Pulse Repetition Rate on Cytokine Secretion from Peripheral Blood Mononuclear Cells in Vitro

Objective: Biological effects of infrared laser energy at various exposure parameters have been characterized in previous in vitro and animal studies. However, the impact of pulse repetition rate (PRR) has not been evaluated in this context. The purpose of this investigation was to assess the influence of PRR on cytokine secretion from peripheral blood mononuclear cells (PBMCs) subjected to pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) laser energy. Materials and Methods: Rat PBMCs were cultured in vitro then stimulated using a lipopolysaccharide concentration of 0 or 100 ng/ml. Cultures received Nd:YAG laser radiation (1064 nm, 5 W, 30 s) at PRR of 0 (untreated controls), 20, 30, 40, or 60 Hz. Concentrations of tumor necrosis factor-α (TNF-α), macrophage inflammatory protein (MIP)-1α, macrophage inflammatory protein (MIP)-2, monocyte chemoattractant protein-1 (MCP-1), interferon-gamma-induced protein (IP)-10, interleukin (IL)-6, and IL-10 were recorded using a magnetic microsphere immunoassay. The main effects of PRR and LPS stimulation on cytokine concentrations, and the interaction between PRR and LPS stimulation, were assessed using two-way analysis of variance. Bonferroni post hoc tests were used to identify pairwise differences between groups. Results: The main effect of PRR was statistically significant for MIP-1α (P = 0.018), TNF-α (P = 0.025), MCP-1 (P &lt; 0.001), MIP-2 (P = 0.013), and IL-6 (P = 0.031). Five of six pro-inflammatory cytokines exhibited significantly lower mean concentrations in laser-exposed compared with control cultures at one or more PRR. However, no statistically significant differences were found between PRR groups. Conclusions: Under the described conditions, statistically significant differences in cytokine secretion were observed between laser-exposed and control cultures, consistent with prior reports. However, PRR appears to be an irrelevant factor in immunomodulation of PBMCs.

Electroacupuncture Therapy Effectively Protects the Rat Brain after Intracerebral Hemorrhage

Objective. Electroacupuncture (Ea) is a useful complementary and alternative therapy for intracerebral hemorrhage (ICH). However, the neurobiological basis for the Ea treatment of ICH is still unclear. The primary aim of the present study was to explore whether Ea prevents brain edema, apoptosis, excitotoxicity, and neuroinflammation in rats after hemorrhagic stroke. Methods. Rats were randomly divided into Sham, Control, and Ea groups. We used modified neurological severity score (mNSS) and gait analysis to estimate neurological function in rats, and PET/CT to assess glucose uptake and the hemorrhagic focus volume. Measurement of the brain water content and TUNEL staining were used to evaluate brain edema and cell apoptosis, respectively. The serum myelin basic protein (MBP), neuron-specific enolase (NSE), calcium-binding protein B (S100B), and tumor necrosis factor-α (TNF-α) concentrations were examined with ELISA. The expression levels of the CD68, GALC, Arg-1, iNOS, NR2A, Glu2R, AQP4, MAP2, GFAP, AQP9, Bcl-2, Bax, and Glu proteins around the hematoma were detected via immunohistochemistry staining. Western blot was used to analyze the levels of the AQP4, AQP9, Bax, Bcl-2, iNOS, and Arg-1 proteins. Results. Ea treatment improved neurological function and reduced the hemorrhagic area and brain water content in rats after ICH. The serum concentrations of MBP, NSE, S100B, and TNF-α all decreased significantly in the Ea group compared with the Control group. Expression levels of the Glu, NR2A, AQP4, AQP9, Bax, GFAP, iNOS, and CD68 proteins in brain tissue surrounding the hematoma were obviously suppressed in ICH rats following Ea treatment. Moreover, Ea stimulation increased the levels of the MAP2, GALC, Glu2R, Arg-1, and Bcl-2 proteins, but reduced the number of TUNEL-positive cells in rats after ICH. Conclusion. The results of this study suggest that Ea may exert neuroprotective effects by suppressing brain edema, apoptosis, excitotoxicity, and neuroinflammation.

Effects of dietary energy level on antioxidant capability, immune function and rectal microbiota in late gestation donkeys.

This study investigated the effects of dietary energy level on the antioxidant capability, immune function, and rectal microbiota in donkey jennets during the last 60 days of gestation. Fifteen pregnant DeZhou donkeys with age of 6.0 ± 0.1 years, body weight of 292 ± 33 kg, parity of 2.7 ± 0.1 parities and similar expected date of confinement (74 ± 4 days) were randomly allocated to three groups and feed three diets: high energy (10.92 MJ/kg, H), medium energy (10.49 MJ/kg, M), and low energy (9.94 MJ/kg, L). The serum activity of catalase (CAT), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in group M was significantly higher, whereas the concentrations of malondialdehyde (MDA), interleukin 1 (IL-1), IL-2, and IL-6 were lower than those recorded for groups H and L (p ≤ 0.05). The dietary energy level significantly affected rectal microbial community structure in the jennet donkeys 35 days and 7 days before the parturition (p ≤ 0.05). The abundances of norank_f_norank_o_Coriobacteriales genus was significantly higher (p ≤ 0.05) in group H, and the abundances of norank_f_norank_o_Mollicutes_RF39 and the Candidatus_Saccharimonas were higher in group L (p ≤ 0.05). The abundance of Fibrobacter in group M was significantly increased (p ≤ 0.05). The abundance of norank_f_norank_o_Coriobacteriales was positively correlated with average daily gain (ADG) and tumor necrosis factor-α (TNF-α) concentrations (p ≤ 0.05). The abundance of norank_f_norank_o_Mollicutes_RF39 was positively correlated with IL-2 and IL-6 concentrations. The abundance of Candidatus_Saccharimonas was positively correlated with CAT, T-SOD and GSH-Px activities (p ≤ 0.05). The abundance of Fibrobacter was positively correlated with CAT and T-SOD activities (p ≤ 0.05), but negatively correlated with IL-2 concentration (p ≤ 0.05). In conclusion, an appropriate dietary with an energy content of 10.49 MJ/kg for jennet donkeys during late gestation increased the prenatal antioxidant capacity, reduced inflammatory cytokines, and promoted fetal growth, and these changes were related to diet-induced changes in rectal microbiota compositions.

A meta-analysis of essential oils as a dietary additive for weaned piglets: Growth performance, antioxidant status, immune response, and intestinal morphology

This study aimed to evaluate the effects of dietary supplementation with EOS on growth performance, blood serum antioxidant status, immune response, and intestinal morphology of weaned piglets using a meta-analytical approach. The database included 31 studies from which the response variables of interest were obtained. All data were analyzed using a random effects model, and results were expressed as weighted mean differences between treatments supplemented with and without EOS. EOS supplementation increased (P < 0.001) average daily feed intake, average daily gain, and final body weight and decreased (P < 0.001) feed conversion ratio and diarrhea incidence. Lower (P = 0.001) serum malondialdehyde content and higher (P < 0.05) serum concentrations of superoxide dismutase, catalase, glutathione peroxidase, and total antioxidant capacity were observed in response to the dietary inclusion of EOS. EOS supplementation increased (P < 0.001) the serum concentration of immunoglobulins A, G, and M and decreased (P < 0.05) the serum concentration of tumor necrosis factor-α, interleukin-1β, and interleukin-6. Greater (P ≤ 0.001) villus height (VH) was observed in the jejunum and ileum in response to the dietary inclusion of EOS. However, EOS supplementation did not affect (P > 0.05) crypt depth (CD) and decreased (P < 0.001) the VH/CD ratio in the duodenum, jejunum, and ileum. In conclusion, essential oils can be used as a dietary additive to improve growth performance and reduce the incidence of diarrhea in weaned piglets and, at the same time, improve the antioxidant status in blood serum, immune response, and intestinal morphology.

Complex interplay of oral health, muscle and bone metabolism, and frailty in older individuals.

To investigate molecular and clinical background of associations among oral health, muscle and bone metabolism, and frailty incidence in patients with fall and fracture history. In total, 88 elderly participants (mean age 71.9 ± 5.8years) with the distal radius fractures were included. Participants were divided into three groups based on an Oral Health Assessment Tool score. Fried criteria and Mini-nutritional assessments were adopted to diagnose frailty and malnutrition, respectively. Blood samples were collected and analyzed for serum levels of bone turnover markers, proteins, insulin-like growth factor-1, 25-hydroxyvitamin D, and inflammatory cytokines. The mRNA levels of markers of inflammation, muscle synthesis and wasting, and muscle homeostasis regulator in the pronator quadratus muscle were analyzed. Patients with deteriorated oral health demonstrated a higher prevalence of frailty and malnutrition. Significantly lower serum levels of total protein and higher concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected in patients with poor oral health. Significant interaction effects between oral health and frailty level in gait speed, serum TNF-α, IL-1β, and total protein levels were exhibited. Significantly different mRNA expression levels in the pronator quadratus muscle of TNF-α, IL-1β, NF kB, MYOG, and FOXO1 following the oral health were detected. This study highlights relationship between oral health, nutritional uptake, systemic inflammation, and their combined impact on muscle and bone metabolism, ultimately affecting frailty development in the aging populations. A comprehensive understanding of mutual interactions among oral health, nutrition, and inflammation is essential for managing frailty.

Protective Effects of Niacin on Rumen Epithelial Cell Barrier Integrity in Heat-Stressed Beef Cattle.

The present study investigates the theoretical basis for maintaining normal physiological functions in heat-stressed beef cattle by exploring the effects of niacin supplementation on the permeability of the rumen epithelial cell barrier. Herein, 12 Jinjiang bulls with an average weight of approximately 400 ± 20.0 kg were randomly divided into three groups, thermoneutral (TN), heat-stressed (HS), and heat-stressed niacin-supplemented (HN) groups, with 4 bulls in each group. The experiment spanned 70 days, and the plasma concentrations of D-lactic acid, diamine oxidase (DAO), lipopolysaccharides (LPSs), and inflammatory cytokines were analyzed. Additionally, we assessed the gene expression of tight junction proteins to understand the effect of niacin supplementation on heat-stressed beef cattle. Our results revealed that heat stress significantly increased the D-lactic acid and LPS levels in beef cattle plasma on days 30 and 45 of the experiment (p < 0.05). Moreover, it led to a significant rise in DAO levels on day 30 (p < 0.05). Niacin supplementation significantly reduced the LPS levels on day 30 (p < 0.05). Heat stress significantly elevated the plasma concentrations of inflammatory cytokines interleukin-1β (IL-1β), IL-2, IL-6, and tumor necrosis factor-α (TNF-α) (p < 0.05), while reducing the IL-4 concentration (p < 0.05). However, niacin supplementation effectively mitigated the concentrations of these inflammatory factors by reducing IL-1β, IL-2, IL-6, and TNF-α concentrations and increasing IL-4 concentrations. The mRNA expressions of tight junction proteins zonula occluden-1 (ZO-1), claudin-1, claudin-4, and claudin-7 were significantly downregulated (p < 0.05) in the HS group compared to those in the TN group, and those of ZO-1 and occludin were significantly upregulated (p < 0.05) in the HN group compared to those in the HS group. Notably, no significant differences were observed in ruminal papillae length and width among the studied groups (p > 0.05). Our findings indicate that heat stress adversely impacted the tight junction structure of the rumen epithelium, leading to a significant reduction in the expression of tight junction protein mRNA. Consequently, heat stress impaired the rumen mucosal barrier function, resulting in increased intestinal permeability. The mechanism underlying this effect may be associated with the decreased expression of tight junction protein genes in the rumen epithelial cells. However, niacin supplementation mitigated the detrimental effects of heat stress on intestinal permeability in beef cattle and increased the expression of tight junction protein genes in the rumen epithelium, thereby effectively protecting the rumen barrier in heat-stressed beef cattle. These results highlight the potential of nicotinic acid as a protective agent against the negative impacts of heat stress on intestinal integrity in beef cattle.

Comparison of neuroprotective effects of a topiramate-loaded biocomposite based on mesoporous silica nanoparticles with pure topiramate against methylphenidate-induced neurodegeneration.

Methylphenidate (MPH) abuse has been criticized for its role in neurodegeneration. Also, a high risk of seizure was reported in the first month of MPH treatment. Topiramate, a broad-spectrum Antiepileptic Drug (AED), has been used as a neuroprotective agent in both aforementioned complications. Nanotechnology is introduced to increase desirable neurological treatment with minimum side effects. We aimed to investigate the potential neuroprotective activity of topiramate loaded on nanoparticles. MTT assay was performed to evaluate the cellular cytotoxicity of Mesoporous Silica Nanoparticles (MSN). Male rats were randomly divided into eight groups. Rats received an intraperitoneal (i.p) MPH (10mg/kg) injection and a daily oral dose of topiramate (TPM, 30mg/kg), MSN with Zn core (10 and 30mg/kg), and MSN with Cu core (10 and 30mg/kg) for three weeks. On day 21, a seizure was induced by a single injection of pentylenetetrazole (PTZ) to evaluate the protective effects of TPM-loaded nanoparticles on seizure latency and duration following MPH-induced neurotoxicity. Moreover, the hippocampal content of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and the anti-oxidant enzymes (SOD, GPx, and GR) activities were assessed. Also, BAX and Bcl-2 as two main apoptotic markers were evaluated. MPH neurotoxicity was observed as a raised duration and reduced latency in PTZ-induced seizure. However, TPM-loaded MSN with Zn species (NE) treatment reduced the duration and improved the latency time. Also, NE and, somewhat, TPM-loaded MSN with Cu species (NM) administration reduced inflammatory cytokines, MDA, and Bax levels and increased activities in the rat hippocampus. TPM-loaded nanoparticles could be used as neuroprotective agents against MPH-induced neurodegeneration by improving seizure parameters and reducing inflammatory, oxidant, and apoptotic factors.

Intersection of Aging and Particulate Matter 2.5 Exposure in Real World: Effects on Inflammation and Endocrine Axis Activities in Rats.

Exposure to particulate matter 2.5 (PM2.5) is detrimental to multiple organ systems. Given the factor that aging also alters the cellularity and response of immune system and dysfunction of hypothalamic-pituitary-adrenal, -gonad and -thyroid axes, it is imperative to investigate whether chronic exposure to PM2.5 interacts with aging in these aspects. In this study, two-months-old Sprague-Dawley rats were exposed to real world PM2.5 for 16 months. PM2.5 exposure diminished the relative numbers of CD4+ T cells and CD8+ T cells and increased the relative number of B cells in the peripheral blood of male rats. Conversely, only reduced relative number of CD4+ T cells was seen in the blood of female rats. These shifts resulted in elevated levels of proinflammatory factors interleukin-6 and tumor necrosis factor-α in the circulatory systems of both sex, with females also evidencing a rise in interleukin-1β levels. Moreover, heightened interleukin-6 was solely discernible in the hippocampus of female subjects, while increased tumor necrosis factor-α concentrations were widespread in female brain regions but confined to the male hypothalamus. Notable hormonal decreases were observed following PM2.5 exposure in both sex. These comprised declines in biomolecules such as corticotrophin-releasing hormone and cortisol, generated by the hypothalamic-pituitary-adrenal axis, and thyroid-releasing hormone and triiodothyronine, produced by the hypothalamic-pituitary-thyroid axis. Hormonal elements such as gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone, derived from the hypothalamic-pituitary-gonad axis, were also diminished. Exclusive to male rats was a reduction in adrenocorticotropic hormone levels, whereas a fall in thyroid-stimulating hormone was unique to female rats. Decreases in sex-specific hormones, including testosterone, estradiol, and progesterone, were also noted. These findings significantly enrich our comprehension of the potential long-term health repercussions associated with PM2.5 interaction particularly among the aging populace.

Comparative evaluation of efficiency of burn wound healing with derma-based hydrogel: a preclinical experimental study

Background. Burn wound healing is recognized as a complex process involving synergetic interactions between different cells, cytokines and growth factors. The adverse interactions can underlie chronicization of the process. Accordingly, the paper presents a relevant study into mechanisms of natural wound dressings, capable of influencing the processes of inflammation, angiogenesis, and skin resurfacing.Objective. To carry out a comparative evaluation of efficiency of burn wound healing with derma-based hydrogel according to the dynamics of proand anti-inflammatory factors.Methods. Development of a hydrogel material involved dermis samples of Landrace breed of pig, subjected to partial alkaline hydrolysis. In order to carry out a comparative evaluation of burn wound healing efficiency, the authors simulated direct thermal injury in three groups of sphinx (hairless) rats: group 1 (control group) — rats without treatment (n = 20), group 2 (comparison group) — rats treated with Levomekol ointment (n = 20), and group 3 (experimental group) — rats treated with hydrogel material (n = 20). Before and after injuring on days 1, 3, 7, 14, the content of cytokines interleukin-1β, interleukin-4, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α by enzyme immunoassay. The wound samples were explanted for histological examination on days 3, 7 and 14 after the beginning of the experiment. Statistical processing of the obtained results on DNA content in hydrogel, cytokine content in serum and morphometric data was performed using GraphPadPrism 6.04, Microsoft Excel 2016 (Microsoft, USA).Results. When determining the content dynamics of nonspecific markers of inflammation, an increase in the concentrations of interleukin-1β and tumor necrosis factor-α on day 1 after the hydrogel application was recorded, as well as an increase in interleukin-6 on days 3 and 7, while the concentrations of interleukin-8 did not change significantly throughout the experiment. Thus, dermal components are indicated to participate in the inhibition of acute-phase immune reactions. With regard to anti-inflammatory factors, the study revealed a decrease in the concentration of interleukin-10 on days 1 and 7, an increase in interleukin-4 on day 3 as compared to the control group, thereby indicating a pronounced anti-inflammatory effect and prolonged action of the hydrogel.Conclusion. Comparative analysis of the pro-inflammatory cytokines levels (interleukin-1β, interleukin-8) showed pronounced anti-inflammatory effects of the derma-based hydrogel material. Introduction of exogenous biological components of the extracellular matrix (collagen and its hydrolysates) had a significant influence on the regulation of anti-inflammatory cytokines synthesis, presumably contributing to faster successful epithelization and wound healing.

Concentrations of serum amyloid A, haptoglobin and some cytokines in calves with Cryptosporidiosis in the pre- and post-treatment stage

This study aims to determine serum amyloid A (SAA), haptoglobin (Hp), interleukin-1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration in cases of Cryptosporidiosis that are frequently encountered in calves in veterinary medicine. Although many experimental studies have been conducted in this field, studies of naturally infected calves are quite a few. In this study, 10 neonatal Holstein calves diagnosed with Cryptosporidium were included. Stool samples were taken from calves with diarrhea using a rapid test kit (BIO-K 313 rapid test kit). Blood samples were obtained from the jugular vein pre- and post-treatment for biochemical measurements. SAA, Hp, IL-1β, IL-6 and TNF-α concentration measurements were conducted with ELISA reader using commercial kits. Calves with Cryptosporidiosis presenting with diarrhea showed a statistical difference in SAA, Hp, IL-1β, IL-6, white blood cell and hemoglobin values before and after treatment, whereas hematocrit, red blood cell and TNF-α concentrations did not show any statistical difference before and after treatment. According to these findings, to follow up the treatment process of calves with Cryptosporidiosis, it is thought that measuring the concentration of SAA, Hp, IL-1β and IL-6 will be useful for determining disease severity, selecting appropriate treatment, following treatment efficacy and determining subclinical diseases.

Effect of acupuncture on the expression of neuropeptides and related inflammatory factors in rats with diarrhea-predominant irritable bowel syndrome.

To observe the effect of acupuncture on the expressions of neuropeptides and related inflammatory factors in rats with diarrhea-predominant irritable bowel syndrome(IBS-D), so as to explore the mechanism of acupuncture in the treatment of IBS-D. Male Wistar rats were randomly divided into blank group, model group, medication group, and acupuncture group, with 6 rats in each group. Except for the blank group, the other groups were subjected to 14-day "acetic acid enema + restraint stress" to establish the IBS-D rat model. After successful modeling, the medication group received gavage of pinaverium bromide(15 mg/kg) once a day, and the acupuncture group received acupuncture at "Baihui"(GV20) and bilateral "Tianshu"(ST25), "Shangjuxu"(ST37), "Zusanli"(ST36), and "Taichong"(LR3) for 20 min every day, both groups were treated continuously for 14 days. The general state of the rats in each group was observed, and the body weight of the rats was measured. The open-field experiment was conducted to measure the horizontal and vertical movements, and the number of fecal pellets of rats. The histopathological morphology of hypothalamus and colon of rats was observed by HE staining. Toluidine blue staining was used to observe and count the mast cells(MCs) in the colon tissue of rats. ELISA was used to detect the serum contents of tumor necrosis factor-α(TNF-α) and interleukin(IL)-10. Real-time fluorescence quantitative PCR was performed to detect the mRNA expressions of calcitonin gene-related peptide(CGRP) in the hypothalamus and colon tissue. Western blot was used to detect the expressions of corticotropin-releasing factor(CRF) in the hypothalamus and colon tissue. HE staining showed that there was inflammatory cell infiltration in the lamina propria of colon in the model group, and it was reduced in the other groups. Compared with the blank group, the model group showed significantly decreased body weight, decreased walking distance and upright times in open field experiment, decreased serum IL-10 contents(P<0.05, P<0.01), increased fecal pellet number (P<0.01), increased MC number in the colon tissue, serum TNF-α contents, and CGRP mRNA expressions and CRF expressions in the hypothalamus and colon tissue(P<0.01). Compared with the model group, both medication and acupuncture groups showed significantly increased body weight, walking distance and upright times in the open-field experiment, and serum IL-10 contents(P<0.01, P<0.05), significantly decreased fecal pellet number (P<0.05), significantly decreased MC number in the colon tissue, serum TNF-α contents, and CGRP mRNA expressions in the hypothalamus and colon tissue(P<0.01)；at the same time, the acupuncture group showed significantly decreased CRF expressions in the hypothalamus and colon tissue(P<0.01, P<0.05). There was no significant difference in the above indicators between the medication group and the acupuncture group. Acupuncture can improve the general and emotional state, inflammatory response, and neuropeptide expression in rats with IBS-D, and alleviate the symptoms of IBS-D, which may be related to the regulation of neuropeptides and inflammatory factors levels.

Mechanism of analgesic effect of fire needle on peripheral sensitization in rats with neuropathic pain induced by chemotherapy.

This study aims to explore the analgesic mechanism of fire needle on peripheral sensitization in rats with neuropathic pain(NP) induced by oxaliplatin, so as to investigate its mechanism in improving peri-pheral sensitization. Male SD rats aged 8 weeks were randomly divided into 4 groups：normal group(n=6), model group(n=6), fire needle group(n=6), and medication group(n=6). NP rat model was established by intraperitoneal injection of oxaliplatin(4 mg/kg) on days 1, 2, 8, 9, 15, 16, 22, and 23. For rats in the fire needle group, fire needle treatment was performed at the "Jiaji"(EX-B2) acupoints of the L4-L6 segments on days 24, 26, and 28, ie. 1 day, 3 and 5 days after modeling. The medication group received intraperitoneal injection of pregabalin(100 mg/kg). Mechanical pain thresholds of the rats were measured before modeling, after modeling and intervention. Serum contents of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and chemokine ligand 12(CXCL12) were detected by ELISA. Skin histopathology changes in the acupoint area were observed using HE staining. The number of mast cells in the skin of the acupoints was observed using toluidine blue staining. Immunohistochemical staining was performed to detect the postive expressions of transient receptor potential vanilloid 1(TRPV1), protease-activated receptor 2(PAR2) and tryptase(TPS) in the skin of the acupoint area. Western blot was used to detect the protein expressions of TRPV1 and PAR2 in the dorsal root ganglia(DRG). Compared with the normal group, the model group had decreased paw withdrawal threshold(PWT) after modeling(P<0.05), increased serum contents of IL-6, TNF-α, and CXCL12(P<0.05), increased number of mast cells in the acupoint area(P<0.05), and increased positive protein expressions of TPS, TRPV1, and PAR2 in the skin of the acupoint area(P<0.05). Compared with the model group, the fire needle group and medication group had increased PWT after intervention(P<0.05), decreased serum contents of IL-6, TNF-α, and CXCL12, and postive protein expressions of TPS, TRPV1, and PAR2 in the skin of the acupoint area(P<0.05)；while the medication group had decreased protein expressions of TRPV1 and PAR2 in DRG(P<0.05). HE staining showed thickened epidermis, disordered cellular arrangement, significant intercellular edema, and inflammatory cell infiltration in the model group. In the medication and fire needle groups, the epidermis was thinner, cellular arrangement was clearer, and the extent of tissue edema and inflammatory cell infiltration was reduced compared to the model group. Fire needle can improve mechanical pain threshold and reduce the contents of peripheral inflammatory factors in rats with oxaliplatin-induced NP. This effect may be related to the inhibition of mast cell activation and the inhibition of TPS, TRPV1 and PAR2 protein expressions, in the local areas of acupoints.

255 Effects of Dietary Valerate Glycerides on Serum Inflammatory Markers, Serum Metabolomic Profile, and Intestinal Mucosa Gene Expression in Weanling Pigs Infected with a Pathogenic Escherichia Coli

Abstract Our previous work showed that dietary valerate glycerides reduced frequency of diarrhea and β-hemolytic coliforms in fecal cultures of pigs infected with F18+ Enterotoxigenic Escherichia coli (ETEC). However, the impact of these feed additives on the immune response and intestinal physiology of newly weaned pigs experiencing ETEC-associated diarrhea has not been evaluated. The present experiment aimed to determine the effects of dietary valerate glycerides on intestinal mucosa gene expression, systemic inflammatory status, and serum metabolomic profile of weanling piglets infected with F18+ ETEC. Sixty weaned piglets (6.97 ± 0.75 kg body weight; 21 days old) were randomly assigned to one of four dietary treatments: nursery basal diet (control), 0.075% or 0.1% monovalerin, or 0.1% trivalerin added to control. After a 7-day adaptation, all piglets were orally inoculated with F18+ ETEC (1010 CFU/3 mL) on d 0, d 1, and d 2 post-inoculation (PI). Serum samples were collected on d 0 prior to ETEC inoculation, d 3, d 6, and d 21 PI to analyze concentration of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and haptoglobin. Serum samples from d 6 PI were submitted for untargeted metabolomics analysis at the West Coast Metabolomics Center. Six replicate pigs per treatment group were euthanized on d 7 PI to collect jejunal and ileal mucosa for gene expression analysis. Data were analyzed in RStudio by ANOVA in a linear mixed model with treatment as fixed effect and pig as random effect. Metabolomics analysis was performed using the online platform, MetaboAnalyst. Pigs fed trivalerin had reduced (P &amp;lt; 0.05) serum TNF-α on d 0 and d 6 PI compared with pigs in control. Whereas pigs supplemented with 0.1% monovalerin tended (P ≤ 0.10) to have decreased serum TNF-α on d 0 and d 3 PI, and less (P &amp;lt; 0.05) serum CRP on d 3 PI compared with pigs in control. No differences in serum concentrations of haptoglobin were detected among dietary treatments. Preliminary results for gene expression analysis indicate a tendency (P = 0.078) for increased mRNA expression of tight junction protein, ZO-1 in pigs fed 0.1% trivalerin compared with control. Among all valerate derivative treatments, significant fold changes [FC &amp;gt; 2, log2(FC) &amp;gt; 1] for individual metabolites were detected, where levels of adenosine, putrescine, and shikimic acid were decreased compared with the control group. No differential metabolomic profiles in serum were identified on d 6 PI as indicated by a lack of cluster separation using principal component analysis (PCA). In conclusion, valerate glycerides could regulate gene expression of the intestinal epithelium and systemic immune response of weanling piglets infected with F18+ ETEC.

Non-peptide orphanin receptor antagonist activity in rat myocardial ischemia-induced cardiac arrhythmias

One of the causes of sudden cardiac death is arrhythmia after acute myocardial ischemia. After ischemia, endogenous orphanin (N/OFQ) plays a role in the development of arrhythmias. It is discussed in this paper how nonpeptide orphanin receptor (ORL1) antagonists such as J-113397, SB-612111 and compound-24 (C-24) affect arrhythmia in rats following acute myocardial ischemia and what the optimal concentrations for these antagonists are. The electrocardiogram of the rat was recorded as part of the experiment. The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the myocardium were measured following euthanasia. Following the use of three antagonists, we found the lowest inflammatory factor concentrations and the smallest number of ischemic arrhythmia episodes. All of them had a small impact on cardiac function. LF/HF values were significantly reduced in all three antagonist groups, suggesting that they are involved in the regulation of sympathetic nerves. In conclusion, pretreatment with the three antagonist groups can effectively reduce the concentration of TNF-α and IL-1β, and the occurrence of arrhythmias after ischemia can also be significantly reduced. Inflammation and sympathetic activity may be related to the mechanism of action of antagonists.