Contents Of Interleukin-6 Research Articles

Association of Short-Chain Fatty Acids with Gut Microbiota and Lipid Metabolism in Mice with Diarrhea Induced by High-Fat Diet in a Fatigued State.

Preliminary research finds that a high-fat diet (HFD) in a fatigued state triggers diarrhea, but the exact mechanism has not been clarified. To address concerns about the pathogenesis of diarrhea, the study evaluates the composition and metabolomics of the gut microbiota. The study uses the multiple platform apparatus device to induce fatigue in mice, combined with intragastric administration of lard-caused diarrhea. Subsequently, the characteristics and interaction relationship of gut microbiota, short-chain fatty acids (SCFAs), inflammatory biomarkers, brain-gut peptides, and lipid metabolism are analyzed at the end of the experiment. HFD in a fatigued state results in a significant increase in interleukin-17, interleukin-6, cholecystokinin, somatostatin, and malondialdehyde content in mice (p < 0.05), along with a substantial decrease in high-density lipoprotein (p < 0.05). Additionally, an HFD in a fatigued state causes changes in the structure and composition of the gut microbiota, with Lactobacillus murinus as its characteristic bacteria, and reduces the production of SCFAs. An HFD in a fatigued state triggers diarrhea, possibly associated with gut content microbiota dysbiosis, SCFAs deprivation, increased inflammation, and dysregulated lipid metabolism.

МАРКЕРЫ РОТОВОЙ ЖИДКОСТИ В ОЦЕНКЕ КЛЕТОЧНОГО СТАРЕНИЯ ПРИ ВОЗРАСТ-АССОЦИИРОВАННЫХ СТОМАТОЛОГИЧЕСКИХ СИНДРОМАХ

This study is devoted to the study of biomarkers of aging in oral fluid in age-associated dental diseases. 63 patients were examined, who were divided into three groups depending on the clinical syndrome: group 1 – occlusive syndrome (increased tooth abrasion, wedge-shaped defects), group 2 – inflammatory periodontal syndrome (chronic generalized periodontitis), group 3 – dystrophic syndrome (leukoplakia, candidiasis stomatitis). The age of patients in these groups was 60–74 years, which corresponds to an elderly age. The control group included 20 healthy volunteers under the age of 40. The content of tumor necrosis factor (TNF), interleukin-6 (IL-6), and protein p53 were determined in the oral fluid. The concentration of these proteins was determined by multiparametric fluorescence analysis with magnetic microspheres (xMAP technology, Luminex 200, USA) using the ProcartaPlex Apoptosis 6-Plex Human ProcartaPlex ™ Panel and ProcartaPlex test systems Human Cytokine/Chemokine (Invitrogen, USA). According to a number of authors, these parameters indirectly characterize the processes of cellular aging. We have identified laboratory markers of oral fluid characteristic of age-associated syndromes, for occlusive syndrome it is salivary TNF, for inflammatory periodontal – TNF and possibly IL-6, for dystrophic syndrome – protein p53. In addition, a correlation was found between age and the severity of the process. These salivary markers can be further considered as candidates for inclusion in laboratory monitoring when evaluating the effectiveness of new technologies for personalized dental treatment of patients of older age groups.

Supplement of exogenous inorganic pyrophosphate inhibits atheromatous calcification in Apolipoprotein E knockout mice

Inorganic pyrophosphate (PPi) is the endogenous inhibitor for vascular calcification (VC). The present study was to investigate the effects of adenosine disodium triphosphate (ADTP) and alendronate sodium (AL), two exogenous PPi sources, on the atheromatous calcification (AC) in Apolipoprotein E knockout (ApoE KO) mice. ApoE KO mice were randomly divided into five groups: ApoE KO group, ApoE KO + ADTP (Low) group, ApoE KO + ADTP (High) group, ApoE KO + AL (Low) group and ApoE KO + AL (High) group. The mice in ApoE KO + ADTP (Low) group and ApoE KO + ADTP (High) group were intraperitoneally injected with ADTP with dose of 0.5 and 1.0 mg/kg/day for 2 months respectively. The mice in ApoE KO + AL (Low) group and ApoE KO + AL (High) group were intraperitoneally injected with AL with dose of 0.6 and 1.2 mg/kg/day for 2 months respectively. The age matched C57 mice were used as control group. All ApoE KO and C57 mice were fed with normal chow throughout the experiment. The calcification was evaluated using von Kossa method. The contents of PPi, triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ) and interleukin-10 (IL-10) as well as the activity of alkaline phosphatase (ALP) in serum were measured. The results showed that compared with C57 mice, ApoE KO mice developed severe AC accompanied with high levels of TC, TG, LDL, IL-6, TNF-α and IFN-γ in serum and with low levels of PPi and IL-10 in serum. Both ADTP and AL dose-dependently reduced the AC in ApoE KO mice compared with that of ApoE mice, without affecting the contents of lipid profiles. In addition, ADTP and AL increased the contents of PPi and IL-10 while decreased the contents of TNF-α, IL-6 and IFN-γ in serum of ApoE KO mice, having no affection on ALP activity. The results suggested that ADTP and AL reduced AC in ApoE KO mice by increasing the PPi level and regulating the inflammation.

Lidocaine nanoparticles alleviate postoperative pain in young mice undergoing cardiovascular closure surgery by inhibiting inflammatory response

One method for treating ventricular septal defect is cardiovascular interventional closure, but the operation is likely to cause inflammation and pain. The inflammatory response is related to inflammatory factors such as interleukin 6 (IL-6) and NF-κB and studies have found that the regulation of inflammation is related to Gq protein. Lidocaine can effectively inhibit the inflammatory response and improve pain. Nanoparticles have on-target stability. Therefore, by constructing lidocaine nanoparticles, this paper explored whether lidocaine nanoparticles could regulate the expression of Gq to mediate NF-κB, regulate the expression of inflammatory factor IL-6, and relieve postoperative pain. Lidocaine nanoparticles were constructed, prepared, and identified, and then injected into the young mice of the experimental group for modeling and grouping. Probes were used to detect the pain threshold of young mice in each group and ELISA kits were used to detect the content of IL-6 in the blood. PCR and Western blot were used to detect the relative levels of Gq, NF-κB, and IL-6. According to the pain threshold, compared with the sham operation group, lidocaine significantly reduced the pain threshold and the reduction effect of the lidocaine nano group was greater than that of the lidocaine aqueous solution group. Lidocaine nanoparticles can inhibit the expression of Gq protein and the reduced Gq expression can inhibit the expression of NF-κB and IL-6. Lidocaine nano group can directly inhibit the expression of Gq protein to inhibit NF-κB signal transduction, thereby reducing the content of IL-6 and the inflammatory response and relieving postoperative pain.

Effect of strontium in drinking water on blood pressure and inflammatory function in hypertension mice

To explore the effect of strontium in drinking water on blood pressure in hypertensive mice and its possible mechanism. Establishment of mouse model of high blood pressure by drinking 2 mg/mL N'nitro-L-arginine methyl eater hydrochloride(L-NAME) for 4 weeks. One hundred ICR mice were randomly divided into normal control group(n=20) and model group(n=80) according to systolic blood pressure. Eighty hypertensive mice were randomly divided into model control group(n=20), 2.5 mg/L strontium water group(n=20), 5.0 mg/L strontium water group(n=20) and 10.0 mg/L strontium water group(n=20). The body weight and blood pressure of mice were measured every week. After 10 weeks, serum sodium(Na), potassium(K), calcium(Ca), magnesium(Mg), Chlorine(Cl), nitric oxide(NO), renin, angiotensin II(Ang II), aldosterone(ALD), endothelial nitric oxide synthase(eNOS), intercellular cell adhesion molecule-1(ICAM-1), heart interleukin-6(IL-6), interleukin-1 beta(IL-1β) and tumor necrosis factor-α(TNF-α) were determined. After 10 weeks of intervention, the systolic blood pressure in the low, medium and high strontium water groups(129.60±4.90 mmHg vs.127.33±6.35 mmHg vs.124.70±3.91 mmHg) was significantly lower than that of the model control group(141.84±5.34 mmHg)(P&lt;0.05). The diastolic blood pressure in the high strontium water group(84.74±5.49 mmHg) was significantly lower than that of the model control group(92.21±10.08 mmHg). The contents of serum potassium, calcium and magnesium in medium strontium gourp(8.06±0.80 mmol/L vs.2.34±0.13 mmol/L vs.0.57±0.12 mmol/L) and high strontium group(9.59±0.58 mmol/L vs. 2.37±0.17 mmol/L vs.0.58±0.09 mmol/L) were significantly higher than those in normal control group(6.64±0.57 mmol/L vs.2.07±0.15 mmol/L vs.0.46±0.10 mmol/L) and model control group(6.62±0.53 mmol/L vs.2.09±0.11 mmol/L vs.0.48±0.09 mmol/L)(P&lt;0.05). Compared with model control group, the contents of renin(24.08±6.65 ng/mL vs.15.24±3.88 ng/mL), AngII(263.30±61.66 pg/mL vs.203.31±54.95 pg/mL), ALD(102.41±22.39 pg/mL vs. 60.31±10.83 pg/mL), ICAM-1(367.17±120.08 ng/mL vs.224.45±46.86 ng/mL), IL-6(5.90±0.66 ng/mL vs.3.88±1.08 ng/mL), IL-1β(6.37±1.83 ng/mL vs.3.44±1.28 ng/mL) and TNF-α(9.35±1.41 ng/mL vs.5.68±2.11 ng/mL) in high strontium group were significantly decreased(P&lt;0.05). Strontium can reduce the blood pressure of hypertensive mice by regulating the eNOS/NO pathway and reducing the production of inflammatory factors.

CHANGES IN MARKERS OF BONE TISSUE REMODELING AND THE INFLAMMATORY PROCESS IN THE BLOOD SERUM OF WHITE RATS IN CASE OF DEFECT FILLING OF THE FEMUR WITH IMPLANTS BASED ON POLYLACTIDE AND TRICALCIUMPHOSPHATE WITH MESENCHYMAL STEM CELLS

Objective. Based on the analysis of markers of inflammation and metabolism of bone tissue in the blood serum of laboratory rats, to evaluate the course of bone remodeling after filling the defect in the distal metaphysis of the femur with 3D-printed implants based on polylactide and tricalcium phosphate (3D-I) alone or in combination with mesenchymal stromal cells (MSCs). Methods. 53 white rats were used, which were divided into groups: intact (5 animals) — the operation was not performed; Control (15) — 3D-I; Experiment I (15) — 3D-I + cultured alloMSCs; Experiment II (15) — 3D-I + introduction of alloMSCs into the area of surgical intervention 7 days after implantation. The following were studied: the content of glycoproteins (GP), interleukin-6 (IL-6), osteocalcin, chondroitin sulfates (CS), total protein, calcium, alkaline (AlP) and acid phosphatase (AP) activity, and their ratio, mineralization indices were calculated. Results. Compared with intact animals, higher indicators were determined in the rats of the Control group: the content of GP by 39.73; 32.88; 23.29 %; CS — 250.00; 222.09 and 196.51 %, AlP activity — 81.67, 51.03, 39.36 %, on the 15th, 30th, and 90th days of the experiment; IL-6 — 44.89; 60.06 % on the 15th and 30th days. In the rats of the Experiment I g roup: the content of GP — by 82.19; 65.75, 57.53 %, IL-6 — 72.14; 96.59; 79.88 %, CS — 306.98; 276.74; 253.49 %; AlP activity — 63.73; 129.70; 51.28 %, on the 15th, 30th and 90th days of the experiment. In the Experiment II group: on the 15th, 30th and 90th days, the content of GP was higher by 27.40; 26.03; 129.18 %; CS — by 175.58; 137.21 and 115.12 %; AlP activity — 192.99; 178.02, 76.31 %; on the 15th and 30th days: IL-6 — by 37.46; 20.74 %. Conclusions. In the case of filling the defect with 3D-printed implants, biochemical signs of moderate inflammation were determined; 3D-printed implants together with MSCs — pronounced inflammation, slowing of bone formation, formation of connective tissue; 3D-printed implants with postoperative injection of MSCs — moderate inflammation and optimal conditions for healing the defect with bone tissue.

Observation of the long-term clinical efficacy of "Fuyang Guben" acupuncture-moxibustion therapy on perennial allergic rhinitis and its effects on the total IgE and IL-4 in the serum

To investigate the long-term clinical efficacy and safety of "Fuyang Guben" (supporting yang and consolidating root) acupuncture-moxibustion therapy on perennial allergic rhinitis (PAR), and to explore its functioning mechanism. The patients with PAR were randomly divided into acupuncture + western medicine group (n=30) and western medicine group (n=30). In the western medicine group, fluticasone propionate nasal spray was administered, one spray in each nostril in one treatment, once a day, for 6 weeks. On the basis of the western medicine group, fuyangguben acupuncture-moxibustion therapy was supplemented. Acupuncture was applied to Shangxing (GV23), Yintang (GV24+), and bilateral Yingxiang (LI20), Shangyingxiang (EX-HN8), Sibai (ST2), Hegu (LI4) and Chize (LU5); warm needling was applied at Dazhui (GV14). The patients of this group received 30 min of acupuncture-moxibustion therapy 3 times weekly during the first 4 weeks and twice a week in the last 2 weeks, totally for 6 weeks. Before treatment, after treatment, in week 10, 18 and 30 of follow-up visits, the reflective total nasal symptom score (rTNSS), the total non-nasal symptom score (TNNSS), the total ophthalmic symptom score (TOSS), and the score of the rhinitis quality of life (RQLQ) scale were compared in the patients of the two groups separately. Using ELISA, the serum concentrations of total immunoglobulin E (IgE) and interleukin-4 (IL-4) were detected before and after treatment. After treatment, the rTNSS, TNNSS, TOSS, as well as RQLQ score were lower in comparison with those before treatment in each group (P<0.05).The rTNSS, TNNSS, TOSS and the score of RQLQ in the week 10, 18 and 30 of follow-up visits were reduced when compared with those before treatment in each group (P<0.05), and these scores in the acupuncture + western medicine group were remarkably lower than those of the western medicine group (P<0.05). After treatment, the serum contents of total IgE and IL-4 were significantly decreased when compared with those before treatment in the acupuncture + western medicine group (P<0.05), and these indicators in the acupuncture + western medicine group were lower than those of the western medicine group (P<0.05). On the base of treatment with fluticasone propionate nasal spray, "Fuyang Guben" acupuncture-moxibustion therapy is safe and effective on PAR, presenting a remarkably long-term efficacy. The functioning mechanism may be related to the down-regulation of total IgE and IL-4 in serum.

Molecular and biochemical investigations of the anti-fatigue effects of tea polyphenols and fruit extracts of Lycium ruthenicum Murr. on mice with exercise-induced fatigue.

Background: The molecular mechanisms regulating the therapeutic effects of plant-based ingredients on the exercise-induced fatigue (EIF) remain unclear. The therapeutic effects of both tea polyphenols (TP) and fruit extracts of Lycium ruthenicum (LR) on mouse model of EIF were investigated. Methods: The variations in the fatigue-related biochemical factors, i.e., lactate dehydrogenase (LDH), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), and interleukin-6 (IL-6), in mouse models of EIF treated with TP and LR were determined. The microRNAs involved in the therapeutic effects of TP and LR on the treatment of mice with EIF were identified using the next-generation sequencing technology. Results: Our results revealed that both TP and LR showed evident anti-inflammatory effect and reduced oxidative stress. In comparison with the control groups, the contents of LDH, TNF-α, IL-6, IL-1β, and IL-2 were significantly decreased and the contents of SOD were significantly increased in the experimental groups treated with either TP or LR. A total of 23 microRNAs (21 upregulated and 2 downregulated) identified for the first time by the high-throughput RNA sequencing were involved in the molecular response to EIF in mice treated with TP and LR. The regulatory functions of these microRNAs in the pathogenesis of EIF in mice were further explored based on Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses with a total of over 20,000-30,000 target genes annotated and 44 metabolic pathways enriched in the experimental groups based on GO and KEGG databases, respectively. Conclusion: Our study revealed the therapeutic effects of TP and LR and identified the microRNAs involved in the molecular mechanisms regulating the EIF in mice, providing strong experimental evidence to support further agricultural development of LR as well as the investigations and applications of TP and LR in the treatment of EIF in humans, including the professional athletes.

Protective Effect of Citrus Medica limonum Essential Oil against Escherichia coli K99-Induced Intestinal Barrier Injury in Mice.

Citrus Medica limonum essential oil (LEO) has been reported to have antibacterial and anti-inflammatory activities, but its protective effect in the intestine remains unknown. In this study, we researched the protective effects of LEO in relation to intestinal inflammation induced by E. coli K99. The mice were pretreated with 300, 600, and 1200 mg/kg LEO and then stimulated with E. coli K99. The results showed that E. coli K99 caused immune organ responses, intestinal tissue injury, and inflammation. LEO pretreatment dose-dependently alleviated these changes by maintaining a low index in the thymus and spleen and producing a high content of immunoglobulin A, G, and M (IgA, IgG, and IgM) and low content of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Intestinal integrity as a consequence of the LEO pretreatment may be related to the high mRNA expression of intestinal trefoil factor (ITF) and the low mRNA expression of transforming growth factor-β1 (TGF-β1). Conclusively, an LEO pretreatment can alleviate E. coli K99-induced diarrhea, immune organ response, and body inflammation in mice by reducing the levels of inflammatory cytokines and improving the levels of immunoglobulin, and the intestinal integrity remained highest when maintaining the high mRNA expression of ITF and keeping the mRNA expression of TGF-β1 low in the intestinal tissue.

Ceftriaxone ameliorates hippocampal synapse loss by inhibiting microglial/macrophages activation in glial glutamate transporter-1 dependent manner in the APP/PS1 mouse model of Alzheimer’s disease

Synapse loss is a major contributor to cognitive dysfunction in Alzheimer’s disease (AD). Impairments in the expression and/or glutamate uptake activity of glia glutamate transporter-1 (GLT-1) contribute to synapse loss in AD. Hence, targeting the restoration of GLT-1 activity may have potential for alleviating synapse loss in AD. Ceftriaxone (Cef) can upregulate the expression and glutamate uptake activity of GLT-1 in many disease models, including those for AD. The present study investigated the effects of Cef on synapse loss and the role of GLT-1 using APP/PS1 transgenic and GLT-1 knockdown APP/PS1 AD mice. Furthermore, the involvement of microglia in the process was investigated due to its important role in synapse loss in AD. We found that Cef treatment significantly ameliorated synapse loss and dendritic degeneration in APP/PS1 AD mice, evidenced by an increased dendritic spine density, decreased dendritic beading density, and upregulated levels of postsynaptic density protein 95 (PSD95) and synaptophysin. The effects of Cef were suppressed by GLT-1 knockdown in GLT-1+/-/APP/PS1 AD mice. Simultaneously, Cef treatment inhibited ionized calcium binding adapter molecule 1 (Iba1) expression, decreased the proportion of CD11b+CD45hi cells, declined interleukin-6 (IL-6) content, and reduced the co-expression of Iba1 with PSD95 or synaptophysin in APP/PS1 AD mice. In conclusion, Cef treatment ameliorated synapse loss and dendritic degeneration in APP/PS1 AD mice in a GLT-1-dependent manner, and the inhibitory effect of Cef on the activation of microglia/macrophages and their phagocytosis for synaptic elements contributed to the mechanism.

Protective effect of Tongdu Tiaoshen acupuncture combined with Xiaoxuming decoction on dopaminergic neurons in Parkinson's disease model.

To explore the possible mechanism of Tongdu Tiaoshen acupuncture combined with Xiaoxuming decoction (, XXMD) in the treatment of Parkinson's disease (PD). C57BL/6 mice were randomly divided into eight groups ( 12), including blank group, model group, medication group, acupuncture group, high-dose XXMD group (XXMD-H), low-dose XXMD group (XXMD-L), acupuncture combined with high-dose XXMD group (A+H), and acupuncture combined with low-dose XXMD group (A+L). After treatment for 6 weeks, dopamine (DA) neurons and the pathological changes of tyrosine hydroxylase (TH) positive cells were observed. The enzyme-linked immunosorbent assay (ELISA) was used to measure the content of DA and the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α). The mRNA level of PINK1 and Parkin and the protein expression of Nix, PINK1 and Parkin in the substantia nigra were also detected. Combination treatment effectively ameliorated the symptoms of PD. Compared with model group, combined treatment significantly up-regulated the protein expression of Nix, Parkin and PINK1 and the mRNA levels of PINK1 and Parkin in the substantia nigra (<0.0001, <0.001, <0.01 or <0.05). Furthermore, the levels of pro-inflammation cytokines were obviously decreased after combination therapy, while IL-10 content was increased remarkably (<0.01). Compared with each treatment alone, combination therapy improved the pathological damage of DA neurons of PD mice more effectively. The possible mechanism may be attributed to the up-regulated level of mitochondrial autophagy and improved mitochondrial function. These results provide fresh insight into the mechanism of co-treatment with Tongdu Tiaoshen acupuncture and XXMD for PD.

Role of IL-6 in the immunopathogenesis of mild, moderate and severe TBI

Traumatic brain injury (TBI) results in a significant inflammatory burden that increase the production of inflammatory mediators and biomarkers. The immune system plays a key role in the pathogenesis of traumatic brain injury. Neuroinflammatory mediators released from resident glia (activated microglia and astrocytes) inside the brain recruit immune cells where cytokines are small soluble proteins that confer instructions and mediate communication among immune and non-immune cells. Interleukin-6 (IL-6) is a proinflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. The purpose of the current study was to assessment of cerebrospinal fluid (CSF) interleukin-6 (IL-6) and MBP levels in patients with TBI. Samples of cerebrospinal fluid of 85 patients with TBI were examined. Concentrations IL-6 were measured via xMAP multiplexing technology. The control was the course of CSF in patients with concussion. An increased content was found in all patients with traumatic brain injury: 19.59 pg/mL in the group with mild traumatic brain injury; 103.6 pg/mL in the group with moderate traumatic brain injury; and 2225 pg/mL in the group with severe traumatic brain injury load versus 2.58 pg/mL in the control group. A direct correlation was found with the presence of basic myelin proteins in the cerebrospinal fluid, which indicates the degree of damage and neurodegeneration processes. Identification of the features of IL-6 content in patients with brain injury may indicate its important role in the course of disease. It also requires additional more detailed study, including comparison with IL-6 content in peripheral blood.

Exploration of the influence of early rehabilitation training on circulating endothelial progenitor cell mobilization in patients with acute ischemic stroke and its related mechanism under a lightweight artificial intelligence algorithm.

This work aimed to explore the application of lightweight artificial intelligence algorithms in magnetic resonance imaging (MRI) image processing of patients with acute ischemic stroke (AIS) to clarify the effect and mechanism of early rehabilitation training on the mobilization of circulating endothelial progenitor cells (EPCs) in AIS. A total of 98 AIS patients undergoing MRI examination were selected as the research objects and were randomly divided into a rehabilitation group (early rehabilitation training, 50 cases) and a routine group (conventional treatment, 48 cases) by random number table method and lottery method. In this work, based on the convolutional neural network (CNN) algorithm, a low-rank decomposition algorithm was introduced to optimize it, and a lightweight MRI image computer intelligent segmentation model (LT-RCNN) was established. The LT-RCNN model was used in the MRI image processing of AIS patients, and the role of the model in AIS image segmentation and lesion localization was analyzed. Furthermore, flow cytometry was used to detect the number of peripheral circulating EPCs and CD34+KDR+ cells in the two groups of patients before and after treatment. The serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin 10 (IL-10), and stromal cell-derived factor-1α (SDF-1α) content were detected by Enzyme-Linked Immunosorbent Assay (ELISA). In addition, the correlation between each factor and CD34+KDR+ was analyzed by Pearson linear correlation. The diffusion-weighted imaging (DWI) signal of MRI images of AIS patients under the LT-RCNN model was high. The location of the lesion could be accurately detected, and the contour of the lesion could be displayed and segmented, and the segmentation accuracy and sensitivity were significantly better than before optimization. The number of EPCs and CD34+KDR+ cells in the rehabilitation group was increased compared with the control group (p<0.01); the expression levels of VEGF, IL-10, and SDF-1α were higher than those of the control group (p<0.001), and TNF-α content was lower than the control group (p<0.001). The number of CD34+KDR+ cells was positively correlated with VEGF, IL-10, and TNF-α contents (p<0.01). The results showed that the computer-intelligent segmentation model LT-RCNN could accurately locate, and segment AIS lesions and the early rehabilitation training could change the expression level of inflammatory factors and further promote the mobilization of AIS circulation EPCs.

Supplementation with Antimicrobial Peptides or a Tannic Acid Can Effectively Replace the Pharmacological Effects of Zinc Oxide in the Early Stages of Weaning Piglets.

Zinc oxide (ZnO) harms the environment and can potentially increase the number of drug-resistant bacteria. Therefore, there is an urgent need to find safe and effective alternatives to improve gut health and reduce the incidence of diarrhea in weaned piglets. This study conducted an antibacterial test of ZnO, antibacterial peptides (AMPs), and tannic acid (TA) in vitro. Thirty piglets were randomly allotted to one of the following three dietary treatments: ZnO (2000 mg/kg ZnO diet), AMPs (700 mg/kg AMPs diet), and TA (1000 mg/kg TA diet). The results showed that the minimum inhibitory concentrations of ZnO and TA against Escherichia coli and Salmonella were lower than those of AMPs, and the minimum inhibitory concentrations of ZnO, AMPs, and TA against Staphylococcus aureus were the same. Compared to ZnO, AMPs increased the digestibility of dry, organic matter and the crude fat. Additionally, TA significantly (p < 0.05) increased the digestibility of dry and organic matter. On experimental day 14, the plasma interleukin-6 (IL-6) content of piglets supplemented with AMPs and TA was increased significantly (p < 0.05). On experimental day 28, alanine aminotransferase activity in the plasma of weaned piglets in the ZnO and TA groups was significantly (p < 0.05) higher than in piglets in the AMPs group. The levels of plasma IL-6 and immunoglobulin M (IgM) were significantly higher (p < 0.05) in the ZnO and AMPs groups than in the TA group. On experimental days 14 and 28, no significant differences were observed in the antioxidant capacity among the three experimental groups. Intestinal microbial diversity analysis showed that the Chao1 and ACE indices of piglets in the AMPs group were significantly higher (p < 0.05) than those in the ZnO and TA groups. At the genus level, the relative abundance of Treponema_2 was higher in the feces of piglets fed a diet supplemented with TA than in those fed diet supplemented with ZnO (p < 0.05). The relative abundance of Lachnospiraceae was higher in the feces of piglets fed a diet supplemented with AMPs than in those fed diet supplemented with ZnO or TA. Overall, AMPs and TA could be added to feed as substitutes for ZnO to reduce diarrhea, improve nutrient digestibility and immunity, and increase the abundance of beneficial intestinal bacteria in weaned piglets.

Nintedanib reduces corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice by increasing the expression of β3 and β6 integrins

Background: Pulmonary fibrosis is a progressive lung disorder that occurs by lung injury and scarring of the lung tissue. This injury makes the lung thickened and stiff causing difficulty to breathe. Corticosteroid resistance pulmonary fibrosis is a major health problem. Bleomycin is an anti-cancer agent, it induces pulmonary fibrosis resistance to corticosteroid therapy, this study aimed to determine the effectiveness of nintedanib (NIN) a tyrosine kinase inhibitor on corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice. Methods: Sixty albino male adult mice were used in this study. The mice were divided into five groups (n=12) at random. control group, the BLM group received a single dose of bleomycin (BLM); 2U/kg by endotracheal instillation, the BLM+MP group received bleomycin and methylprednisolone (MP) 10mg/kg/day by gastric gavage, BLM+NIN group received BLM and NIN, 60mg/kg/day by gastric gavage and the combined treatment group received BLM, NIN, and MP. All groups were sacrificed after the last dose of treatment on day 7 (acute stage) and day 28 (chronic stage). The lung tissues were obtained for biochemical analysis, gene expression, and histopathological examination at the end of the experiment. Results: After 7 days of treatments, BLM+NIN and BLM + NIN + MP groups showed a significant (P&lt;0.05) decrease in the contents of interleukin-2, interleukin-4, interferon-gamma, tumor necrosis factor-alpha, Malondialdehyde with an increase in the glutathione content in lung tissue compared to MP group. Also, they showed a significant decrease in the lung water content compared to the BLM group treated with MP. After 28 days, both NIN groups showed a significant reduction in hydroxyproline, and transforming growth factor beta (β) contents in the lung tissues compared to the MP group, and they showed a positive effect on the expression of β3 and β6 integrins compared to the negative effect of the MP group. Upon histopathology examination, the BLM+NIN group and BLM + NIN + MP groups showed significant improvement compared to the MP group by hematoxylin and eosin (H and E) and Masson’s trichrome stains. Immunohistochemical staining revealed negative BCL-2 expression in the cytoplasm of bronchiolar epithelium in BLM+NIN and BLM + NIN + MP groups after 7 and 28 days of treatment. Morphometric studies of lung tissue showed significant improvement in pathological changes induced by BLM in the BLM+NIN group and BLM + NIN + MP groups. Conclusion: Altogether, our data indicate that NIN overcame corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice mainly by decreasing TGF-β and improving the expression of β3 and β6 integrins.

Blidingia sp. extracts improve intestinal health and reduce diarrhoea in weanling piglets.

Blidingia sp. is a prominent fouling green macroalga and we previously found that extracts from Blidingia sp. alleviated intestinal inflammation in mice challenged with lipopolysaccharides. However, whether these extracts are effective in weanling piglets remains unknown. In the present study, Blidingia sp. extracts were supplemented in the diet and their effects on growth performance, incidence of diarrhoea and intestinal function in weanling piglets were explored. The results showed that diets supplemented with 0.1% or 0.5% Blidingia sp. extract significantly increased average daily body weight gain and feed intake in weanling piglets. Meanwhile, piglets supplemented with 0.5% Blidingia sp. extract showed decreased incidence of diarrhoea as well as reduced fecal water and Na+ content. Furthermore, the diet supplemented with 0.5% Blidingia sp. extracts improved intestinal morphology, as indicated by the results of hematoxylin and eosin staining. Diet supplemented with 0.5% Blidingia sp. extracts also improved tight junction function, as indicated by increased expression of Occludin, Claudin-1 and Zonula occludens-1, and alleviated the inflammatory response, as indicated by decreased tumor necrosis factor-α and interleukin-6 (IL6) contents and increased IL10 levels. Taken together, our results showed that Blidingia sp. extracts had beneficial effects in weanling piglets and we suggest that Blidingia sp. extracts could be potentially used as an additive for piglets.

The Effect of Dietary Supplementation with Zinc Amino Acids on Immunity, Antioxidant Capacity, and Gut Microbiota Composition in Calves.

The aim of this study was to investigate the effect of dietary supplementation with zinc (Zn) amino acids at different concentrations on immunity, antioxidant capacity, and gut microbiota composition in calves. Twenty-four one-month-old healthy Angus calves of comparable body weight were randomly divided into three groups (four males and four females in each group) based on the amount of Zn supplementation added to the feed the animals received: group A, 40 mg/kg DM; group B, 80 mg/kg DM; and group C, 120 mg/kg DM. The experiment ended when calves reached three months of age (weaning period). The increase in dietary Zn amino acid content promoted the growth of calves, and the average daily weight gain increased by 36.58% (p < 0.05) in group C compared with group A. With the increase in the content of dietary Zn amino acids, the indexes of serum immune functions initially increased and then decreased; in particular, the content of immunoglobulin M in group A and group B was higher than that in group C (p < 0.05), whereas the content of interleukin-2 in group B was higher than that in the other two groups (p < 0.05). In addition, the content of superoxide dismutase and total antioxidant capacity in the serum of calves in group B was higher than that in group C (p < 0.05), and the MDA level was lower than in group C (p < 0.05). Moreover, alpha diversity in the gut microbiota of calves in group B was higher than that in group A and group C (p < 0.05); the dominant phyla were Firmicutes and Bacteroidota, whereas the dominant genera were Unclassified-Lachnospiraceae and Ruminococcus. Linear discriminant analysis showed that the relative abundance of Bacteroides in the gut microbiota of calves in group B was higher than that in group A, and the relative abundance of Prevotellaceae-UCG-003 was higher compared to that in experimental group C. Thus, dietary supplementation of 80 mg/kg of Zn amino acids to calves could improve the immune function and antioxidant capacity, as well as enrich and regulate the equilibrium of gut microbiota, thus promoting the healthy growth of calves.

Protective effects of oridonin against osteoporosis by regulating immunity and activating the Wnt3a/β-catenin/VEGF pathway in ovariectomized mice

This study was performed with the aim of investigating the effect of oridonin (ORI) on estrogen deprivation-induced osteoporosis in mice and its mechanism. Animal experiments were used in this work to validate the anti-osteoporotic efficacy of ORI. Morphometric analysis was performed by micro-CT. A special protein meter was used to detect the content of immunoglobulin lgM, immunoglobulin lgG, complement C3 and C4 in the serum of mice. The expression of CD4+CD25+Foxp3+ Treg cell and CD4+/CD8+ lymphocyte subsets in mice was detected by flow cytometry. ELISA was used to detect the content of insulin-like growth factor (IGF-1), tumor necrosis factor (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6). In addition, key signaling molecules in the Wnt3a/β-catenin signaling pathway were detected by Western blotting. The results showed that compared with the model group, the contents of calcium and phosphorus in the femurs of mice in the ORI groups were increased, and the spleen coefficient was decreased. The ALP activity in the serum of mice in the high and medium dose ORI groups was decreased, and the uterine coefficient was increased. ORI significantly increased the maximum bending load and the maximum bending stress of the femurs of mice, increased the number of trabeculae, and repaired the bone microstructure. At the same time, ORI could significantly increase the levels of immunoglobulin (lgG and lgM) and complement (C3 and C4), increase the activity of peritoneal macrophages in mice, increase the expression of CD4+CD25+Foxp3+ Tregs and CD4+/CD8+ in the spleen, increase the content of IGF-1, reduce the content of TNF-α, IL-1 and IL-6 and increase the expression levels of VEGF, Wnt3a, p-GSK3β/GSK3β and β-catenin/Lamin in the femoral tissue. These results indicated that ORI might regulate the expression of VEGF through the Wnt3a/β-catenin signaling pathway, improve the immunity of mice, maintain the balance of the immune system, and promote angiogenesis, thereby improving the bone mineral density and bone tissue morphology of mice and playing an anti-osteoporotic role.

Lycium barbarum polysaccharide reduces lung cancer immunotherapy-related endocrine adverse reactions and improves prognosis via interleukin-2

This paper studies the mechanism of Lycium barbarum polysaccharide (LBP) in adverse reactions after immunotherapy. Five groups including model group, low-dose LBP group, middle-dose LBP group, high-dose LBP group, and interleukin-2 (IL-2) inhibitor group were set up. Adverse reactions after immunotherapy were observed through staining, blood collection and related experiments. IL-2 content was detected by ELISA, RT-qPCR and Western blot. The correlation coefficient between adverse reactions and prognosis was analyzed by Pearson software. LBP improved the diarrhea after immunotherapy and inhibition of IL-2 made the diarrhea more serious. Neutrophils around the hair follicles in the high-dose LBP group were less while they were more in model group where the hair follicles were blocked. The follicles in model group were more swelled while the follicles of high-dose LBP group had fewer swollen follicles. The degree of liver damage was inversely proportional to the concentration of LBP and the inhibition of IL-2 increased liver damage. The increased LBP promoted the improvement of immune function. LBP had a positive correlation with IL-2 level. The expression of IL-2 and E-cadherin increased with increased LBP concentration. Further analysis showed a negative correlation between diarrhea, ALT activity and AST activity and E-cadherin expression. Positive correlation between CD4+/CD8+ level and E-cadherin was observed. Conclusively, LBP could reduce adverse reactions after immunotherapy and promote IL-2 expression. IL-2 is related to immune function and its decrease causes more serious adverse reactions after immunotherapy. Thus, LBP can control IL-2 expression to reduce the adverse reactions after immunotherapy.

Moxibustion relieves colonic inflammation by up-regulating expression of miR-345-3p/miR-216a-5p and down-regulating NF-κB p65 in colonic tissue of rats with diarrhea-predominant irritable bowel syndrome

To observe the effect of moxibustion on the expression of miR-345-3p, miR-216a-5p and nuclear factor-κB p65(NF-κB p65) in colonic tissue of rats with diarrhea-predominant irritable bowel syndrome (IBS-D), so as to explore its anti-inflammatory mechanism in relieving IBS-D. SD rats were randomly divided into normal control (n=12), model (n=12), moxibustion (n=12) and ammonium pyrrolidine dithiocarbamate (PDTC,n=12) groups. The IBS-D model was established by neonatal mother-child separation combined with acetic acid enema stimulation and chronic binding methods. The rats in the moxibustion group received moxibustion stimulation of "Tianshu"(ST25) and "Shangjuxu"(ST37) for 20 min, once a day, for 7 days, and those of the PDTC group received intraperitoneal injection of PDTC (50 mg·kg-1·d-1) once daily for 7 days. After the intervention, the body weight, loose stool rate and the minimum volume threshold of abdominal withdrawal reflex (AWR) were observed, and histopathological changes of colonic mucosa were observed by HE staining. The contents of interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6) and tumor necrosis factor α (TNF- α) in serum were measured by ELISA. The expression of miR-345-3p, miR-216a-5p and NF-κB p65 mRNA in the colon tissue were detected by quantitative real-time PCR, and the immunoactivities of IL-1β, IL-6, TNF-α and NF-κB p65 in the colon tissue were determined by immunofluorescence histochemistry. Compared with the normal control group, the loose stool rate, contents of IL-1β, IL-6 and TNF-α, experssion of NF-κB p65 mRNA and the immunoactivities of IL-1β, IL-6, TNF-α and NF-κB p65 were significantly increased (P<0.01), whereas the body weight, minimum volume threshold of AWR, content of IL-4, and the relative expression of miR-345-3p and miR-216a-5p were remarkably decreased in the model group (P<0.01). In comparison with the model group, the loose stool rate, contents of IL-1β, IL-6, TNF-α, expression of NF-κB p65 mRNA and the immunoactivities of IL-1β, IL-6, TNF-α and NF-κB p65 were considerably down-regulated (P<0.01), while the content of IL-4 and the relative expressions of miR-345-3p and miR-216a-5p were obviously up-regulated in both moxibustion and PDTC groups (P<0.01, P<0.05). The content of IL-6 in serum was significantly lower in the PDTC group than in the moxibustion group (P<0.01). Moxibustion can reduce the level of intestinal inflammation and visceral hypersensitivity in IBS-D rats, which may be related to its functions in increasing the expression levels of miR-345-3p and miR-216a-5p and in inhibiting the expression of NF-κB p65, thus reducing the levels of inflammatory factors.