Contents Of Interleukin-6 Research Articles

Study on mechanism of Aconitum pendulum in treating rheumatoid arthritis based on toxicity efficacy evaluation and metabonomics

The study aims to investigate the effects and potential mechanism of raw and processed Aconitum pendulum Busch on rheumatoid arthritis(RA) and analyze their toxicity attenuating and efficacy retaining effects. The bovine type Ⅱ collagen-induced arthritis(CIA) rat model was established. The weight, cardiac index, immune organ index, and arthritis index of the rats were recorded and calculated after administration. ELISA was used to measure the expressions of creatine kinase(CK), cardiac troponin T(cTnT), and multiple factors. The pathological morphological changes in heart tissue and ankle joint tissue were observed by hematoxylin-eosin staining. Connexin 43(Cx43) expression in the hearts of CIA rats was detected via immunohistochemical method. The levels of endogenous metabolites in the serum of CIA rats were detected by UPLC-Q-TOF-MS. Potential biomarkers were screened, and related metabolic pathways were analyzed. The results showed that raw A. pendulum could induce local myocardial fiber degeneration and necrosis, increase the cardiac index, decrease the average positive area of Cx43 expression significantly, and increase the expressions of CK and cTnT in cardiac tissue of rats. Meanwhile, raw A. pendulum could decrease the immune organ index, interleukin-6(IL-6), and other inflammatory cytokine contents in the serum and improve the damaged synovium and joint surface of CIA rats, with toxicity and efficacy coexisting. The Zanba stir-fired A. pendulum could reduce the index of arthritis, immune organ index, and content of IL-6 and inflammatory cytokines in serum and improve damaged synovium and joint surface of CIA rats with no obvious cardiac toxicity, showing significant toxicity attenuating and efficacy retaining effects. A total of 19 potential biomarkers of raw A. pendulum and Zanba stir-fired A. pendulum against RA were screened by serum metabolomics, including glycerophospholipid metabolism, glycine, serine, and threonine metabolism, arginine and proline metabolism, and steroid hormone synthesis. In conclusion, Xizang medicine A. pendulum is preventive and curative for RA. Raw A. pendulum has certain cardiotoxicity, and Zanba stir-fired A. pendulum has significant toxicity attenuating and efficacy retaining effects. The anti-RA mechanism may be related to the regulation of glycerophospholipid and amino acid metabolism.

The content of lactoferrin and interleukin-8 in breast milk of patients with lactational mastitis

Introduction and aim. Information concerning lactoferrin and interleukin-8 (IL-8) local levels in breast milk are not numerous and requires further research. The aim of this study was to determine the content of lactoferrin and interleukin-8 in the breast milk of patients with lactational mastitis, and to identify new potential markers for assessing the activity of the inflammatory process in the mammary gland. Material and methods. This study analyzed the breast milk of 30 women with lactostasis (group I), 37 women with lactational mastitis (group II) and 30 healthy lactating women (age 26±5 years old). The milk content of lactoferrin and interleukin-8 (IL-8) was determined by enzyme-linked immunosorbent assay. Results. The average value of lactoferrin in breast milk of healthy women was 4.78±0.47 mg/mL, exceeding levels in group I 1.8 times (p<0.05). The level of lactoferrin in group II exceeds the control values 3.1 times (p<0.05). The content of IL-8 in breast milk of women in group I was 7.3 times higher than the control (3.63±0.12 pg/mL, p<0.05). In lactational mastitis, the concentration of IL-8 in breast milk exceeded the group I 13.9 times (p<0.05) and was 1.9 times higher than group I (p<0.05). Conclusion. The analysis has revealed an increase of lactoferrin and IL-8 in breast milk of the test groups, which indicates the activation of non-specific protection.

Interleukin 8 and bronchial phagocytes in patients with non-allergic asthma and diverse respiratory responses to cold stimulus

Introduction. The role of phagocytes, regulated by interleukin 8 (IL-8), in the formation of the bronchial response to environmental stimuli in patients with asthma is not well understood.Aim. To study the functional activity of IL-8 and the pool of phagocytic cells in the inflammatory pattern of the bronchi in patients with non-allergic asthma during inhalation exposure to cold air.Materials and methods. In 129 patients with mild to moderate asthma, the content of IL-8 and the cellular composition of sputum before and after the bronchoprovocation test with isocapnic hyperventilation with cold air (-20°C) (IHCA) were analyzed.Results. Based on the results of the IHCA by the assessment of changes in FEV1 (Δ,%), 54 patients (1st group) were verified with cold airway hyperresponsiveness (CAHR), the comparison group consisted of asthma patients (2nd group, n=75) who did not respond to the trigger (ΔFEV1 = -18.9±1.2 and -3.3±0.4%; p<0.0001, respectively). The content of neutrophils in sputum before provocation was 41.1±2.2% and 34.5±2.2% (p><0.05), macrophages – 36.2±2.7% and 43.1±2.5% (p> ˂ 0.0001, respectively). The content of neutrophils in sputum before provocation was 41.1±2.2% and 34.5±2.2% (p ˂ 0.05), macrophages – 36.2±2.7% and 43.1±2.5% (p>0.05), respectively. In response to the IHCA in the 1st group, the number of neutrophils increased to 48.2±2.0% (p ˂ 0.05), macrophages decreased to 28.7±2.1% (p ˂ 0.01), and the level of IL-8 increased from 12838±2328 to 17412±2980 pg/mL (p ˂ 0.05). In the 2nd group, the concentration of IL-8 before the IHCA was 14639±2691 pg/mL, after the test 10545±1746 pg/mL (p>0.05); the number of neutrophils after the test 40.0±2.3% (p>0.05); macrophages – 35.8±2.0% (p ˂ 0.01).Conclusion. In asthma patients with CAHR, the inflammatory pattern of the bronchi in response to the cold trigger shows enhanced IL-8 activity and more pronounced changes in the content of phagocytes, mobilized with the involvement of this cytokine.

Attenuating Renal Interstitial Fibrosis by Shenqi Pill viaReducing Inflammation Response Regulated by NF-κBPathway In Vitro and In Vivo.

One of the most significant clinical features of chronic kidney disease is renal interstitial fibrosis (RIF). This study aimed to investigate the role and mechanism of Shenqi Pill (SQP) on RIF. RIF model was established by conducting unilateral ureteral obstruction (UUO) surgery on rat or stimulating human kidney-2 (HK-2) cell with transforming growth factor β1 (TGFβ1). After modeling, the rats in the SQP low dose group (SQP-L), SQP middle dose group (SQP-M) and SQP high dose group (SQP-H) were treated with SQP at 1.5, 3 or 6 g/kg/d, and the cells in the TGFβ1+SQP-L/M/H were treated with 2.5%, 5%, 10% SQP-containing serum. In in vivo assays, serum creatinine (SCr) and blood urea nitrogen (BUN) content were measured, kidney histopathology was evaluated., and α-smooth muscle actin (α-SMA) expression was detected by immunohistochemistry. Interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) content, inhibitor of kappa B alpha (IKBα) and P65 phosphorylation were assessed. Meanwhile, cell viability, inflammatory cytokines content, α-SMA expression, IKBα and P65 phosphorylation were detected in vitro experiment. Results. SQP exhibited reno-protective effect by decreasing SCr and BUN content, improving renal interstitial damage, blunting fibronectin (FN) and α-SMA expression in RIF rats. Similarly, after the treatment with SQP-containing serum, viability and α-SMA expression were remarkably decreased in TGFβ1-stimulated HK-2 cell. Furthermore, SQP markedly down-regulated IL-1β, IL-6, and TNF-α content, IKBα and RelA (P65) phosphorylation both in vivo and in vitro. Conclusion. SQP has a reno-protective effect against RIF in vivo and in vitro, and the effect is partly linked to nuclear factor-kappa B (NF-κB) pathway related inflammatory response, which indicates that SQP may be a candidate drug for RIF. DOI: 10.52547/ijkd.7546.

Evaluation of the Level of Serum Interleukin-10 Depending on the Demographic and General Clinical and Laboratory Characteristics of the Coronavirus Disease-19 in Hospitalized Patients

Evaluation of the Level of Serum Interleukin-10 Depending on the Demographic and General Clinical and Laboratory Characteristics of the Coronavirus Disease-19 in Hospitalized Patients

Protective effects of functional Nano-Selenium supplementation on spleen injury through regulation of p38 MAPK and NF-κB protein expression

Selenium (Se) is a trace element necessary for humans to maintain normal physiological activities, and Se deficiency may lead to splenic injury, while Se supplementation can alleviate splenic injury. However, the mechanism is unclear. In this study, we constructed a Se deficiency animal model by feeding Sprague-Dawley (SD) rats with low Se feed. Meanwhile, we observed the repairing effect of Se supplementation on splenic injury with two doses of novel nano-selenium (Nano-Se) supplement by gavage. We measured the Se content in the spleens of the rats by atomic fluorescence spectroscopy (AFS) method and combined the results of hematoxylin-eosin (HE) and Masson staining to observe the splenic injury, comprehensively evaluating the construction of the animal model of low selenium-induced splenic injury. We measured the mRNA and protein expression levels of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa-B (NF-κB), and interleukin-6 (IL-6) in the spleen by Real-time quantitative polymerase chain reaction (qPCR), western blot (WB), and immunohistochemistry (IHC). We found that the Se deficiency group exhibited lower Se content, splenic fibrosis, and high expression of p38 MAPK, NF-κB, and IL-6 compared to the normal group. The Se supplement groups exhibited higher Se content, attenuated splenic injury, and down-regulated expression of p38 MAPK, NF-κB, and IL-6 relative to the Se deficiency group. This study suggests that Se deficiency leads to splenic injury in rats, and Se supplementation may attenuate splenic injury by inhibiting the expression of p38 MAPK, NF-κB and IL-6.

Effects of natural extract from medicinal herbs on broilers experimentally infected with Eimeria tenella

This study aimed to evaluate the effects of natural extracts from nine medicinal herbs (SMA) on the growth performance, immunity, and intestinal integrity of broilers experimentally infected with Eimeria tenella. A total of 252 one-day-old broiler chicks were divided into 7 groups with 3 replicates per group and 12 broilers per cage. The groups were uninfected–untreated blank control group (BC), infected–untreated negative control group (NC), SMA treatment groups, Chinese medicine positive control group (CM), and chemical drug positive control group (CD). The SMA groups were infected and fed a basal diet supplemented with 0.6 (SMA-L), 0.8 (SMA-M), and 1.0 (SMA-H) g/kg SMA. The CM and CD groups were infected and fed a basal diet supplemented with 15 g/kg Jiqiuchong San and 0.2 g/kg Diclazuril, respectively. Results showed that feeding SMA could significantly reduce the number of oocysts in infected chickens, especially 1.0 g/kg SMA, which exhibited moderate anticoccidial efficacy. When infected with E. tenella, the supplementation of 1.0 g/kg SMA increased the renal index; restored the hepatic, splenic, and bursal indexes to BC levels; increased the levels of immunoglobulin A (IgA), IgM, and IgY; and reduced the contents of tumor necrosis factor (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), and IL-10 of the infected chickens. Moreover, treatment with 1.0 g/kg SMA alleviated the pathological changes in cecal tissue and increased the contents of zonula occludens-1 (ZO-1), occludin, claudin-1, and mucoprotein 2 (mucin-2) in cecal tissues of E. tenella-infected chickens. We found that 1.0 g/kg SMA reduced the number of oocysts, improved immunity, and alleviated intestinal barrier damage, which could improve the growth performance of infected chickens. Thus, SMA proved to be an effective natural extract against E. tenella and has the potential to be used as an efficient anticoccidial drug or additive.

The role of the SIRT1-BMAL1 pathway in regulating oxidative stress in the early development of ischaemic stroke

Oxidative stress is the primary cause of ischaemic stroke and is closely related to circadian rhythm. However, the mechanism by which circadian rhythm regulates oxidative stress in ischaemic stroke remains elusive. The Silent Information Regulator 1 (SIRT1) controls circadian rhythm by activating the transcription of the circadian clock core protein Basic Helix-Loop-Helix ARNT Like 1 (BMAL1) through deacetylation. Studies have shown that the SIRT1-BMAL1 pathway can regulate oxidative stress. To investigate its correlation with oxidative stress, we examined the expression levels and influencing factors of SIRT1-BMAL1 at different times in ischaemic stroke patients and analyzed their clinical indexes, oxidative stress, and inflammatory factor indicators. The expression levels of oxidative stress and inflammatory factor indicators, including malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-α), SIRT1, and BMAL1, were detected in ischaemic stroke patients within 4.5 h of onset and in non-stroke patients. Patients were divided into four subgroups based on onset time: subgroup 1 (0:00–05:59); subgroup 2 (06:00–11:59); subgroup 3 (12:00–17: 59); and subgroup 4 (18:00–23:59). Our results showed higher MDA, IL-6, and TNF-α levels, and lower SOD, SIRT1, and BMAL1 levels in ischaemic stroke patients compared to control patients (P < 0.05). Among the four subgroups, the content of MDA, IL-6, and TNF-α was highest in patients with ischaemic stroke onset from subgroup 2 (06:00–11:59), while the expression levels of SOD, BMAL1, and SIRT1 were lowest in patients with ischaemic stroke in subgroup 2. Additionally, myeloperoxidase (MPO) reached the highest value showing the same trends consistent with MDA, IL-6, and TNF-ɑ and opposite trends consistent with SOD, BMAL1, and SIRT1. However, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), immediate blood glucose, immediate diastolic blood pressure, immediate systolic blood pressure, and homocysteine (HCY) did not show any statistically significant circadian rhythm changes (P > 0.05). Our findings suggest that the SIRT1-BMAL1 pathway may be involved in early oxidative stress in ischaemic stroke, which may be related to MPO.

Effects of dietary Nisin on growth performance, immune function, and gut health of broilers challenged by Clostridium perfringens.

Nisin (Ni) is a polypeptide bacteriocin produced by lactic streptococci (probiotics) that can inhibit the majority of gram-positive bacteria, and improve the growth performance of broilers, and exert antioxidative and anti-inflammatory properties. The present study investigated the potential preventive effect of Nisin on necrotic enteritis induced by Clostridium perfringens (Cp) challenge. A total of 288 Arbor Acres broiler chickens of 1-d-olds were allocated using 2 × 2 factorial arrangement into four groups with six replicates (12 chickens per replicate), including: (1) control group (Con, basal diet), (2) Cp challenge group (Cp, basal diet + 1.0 × 108 CFU/mL Cp), (3) Ni group (Ni, basal diet + 100mg/kg Ni), and (4) Ni + Cp group (Ni + Cp, basal diet + 100mg/kg Ni + 1.0 × 108 CFU/mL Cp). The results showed that Cp challenge decreased the average daily gain (ADG) of days 15 to 21 (P<0.05) and increased interleukin-6 (IL-6) content in the serum (P < 0.05), as well as a significant reduction in villus height (VH) and the ratio of VH to crypt depth (VCR) (P<0.05) and a significant increase in crypt depth (CD) of jejunum (P<0.05). Furthermore, the mRNA expressions of Occludin and Claudin-1 were downregulated (P<0.05), while the mRNA expressions of Caspase3, Caspase9, Bax, and Bax/Bcl-2 were upregulated (P<0.05) in the jejunum. However, the inclusion of dietary Ni supplementation significantly improved body weight (BW) on days 21 and 28, ADG of days 15 to 21 (P<0.05), decreased CD in the jejunum, and reduced tumor necrosis factor-α (TNF-α) content in the serum (P<0.05). Ni addition upregulated the mRNA levels of Claudin-1 expression and downregulated the mRNA expression levels of Caspase9 in the jejunum (P<0.05). Moreover, Cp challenge and Ni altered the cecal microbiota composition, which manifested that Cp challenge decreased the relative abundance of phylum Fusobacteriota and increased Shannon index (P<0.05) and the trend of phylum Proteobacteria (0.05<P<0.10), while Ni addition increased the relative abundance of phylum Cyanobacteria (P<0.05). In conclusion, the results demonstrated that the addition of Ni effectively mitigated the negative impact of Cp challenge-induced the damage of growth performance and intestine in broilers via reducing inflammatory responses and intestinal apoptosis and modulating cecal microbial composition.

Динамика клинических и иммунологических показателей при патогенетической терапии острого или обострения хронического фарингита

Objective. To study the anti-inflammatory properties of Tonsilgon N preparation and its effect on the indices of local immunity of oropharyngeal mucosa in patients with acute or exacerbation of chronic pharyngitis without a pronounced systemic inflammatory syndrome. Patients and methods. 60 people diagnosed with acute catarrhal pharyngitis with intoxication syndrome were examined. Group 1 – 30 people took the drug Tonsilgon N in the form of alcohol solution, group 2 – 30 people – sage in the form of tablets for resorption in the oral cavity according to the scheme of 25 drops or 1 tablet every 2 hours for the first 3 days of treatment, then 3 times a day until day 7 inclusive. Pharyngoscopy was performed by an otorhinolaryngologist at each visit on day 1, day 3–4 and day 7–8 of the disease. Using a 10-point visual analogue scale (VAS) with scores from 0 (no sign) to 10, we evaluated the severity of symptoms (pain when swallowing, a feeling of parching in the oropharynx, a feeling of a foreign body in the oropharynx, dry cough, weakness, headache) and the condition of the oropharyngeal mucosa. Additionally, at 3 visits, scrapings from the oropharyngeal mucosa were made with a cytobrush probe and the content of IL-6 and sIgA proteins was determined by enzyme immunoassay. For the control group, 30 conventionally healthy people were taken, not differing in sex and age from the main group of patients and having no inclusion criteria. Results. All patients by day 7 of observation had no expressed complaints, none of them had progression of inflammatory process or development of any complications, patients did not need further continuation of treatment. Pain at swallowing, feelings of foreign body in the oropharynx, feelings of feathering and intensity of hyperemia of the mucous membrane of the posterior pharyngeal wall when treated with Tonsilgon N on the 3–4 day of observation compared to the group of patients taking Sage. On the 7th day of observation at Tonsilgon N treatment all analyzed clinical manifestations of pharyngitis were absent, and in Sage group in some cases weakly expressed symptoms of pain at swallowing, feeling of foreign body in the oropharynx, feeling of fever, intensity of hyperemia of the mucous membrane of the back wall of the pharynx (Me = 0 [0;1] points) and dry cough (Me = 0 [0;0.5] points) remained. On day 1 of observation, an increase in IL-6 protein content compared with normal was noted in pharyngitis, and sIgA levels were low. Further, both groups showed a decrease in IL-6 level, in group 1 in the group receiving Tonsilgon N, its level on the 2nd and 3rd visit was lower compared to group 2. The amount of sIgA on the first day with pharyngitis was minimal, then in group 1 its values increased on day 3 but remained below control, and in group 2 further decreased, on day 7 of observation in group 1 sIgA slightly increased but was below control. In group 2 the sIgA level was determined in minimal values. Conclusion. Tonsilgon N or sage therapy showed a clear relief of clinical symptoms of tonsillopharyngitis during the treatment period without taking non-steroidal anti-inflammatory drugs, and their reduction was significantly faster with Tonsilgon N. Decrease of proinflammatory cytokine IL-6 on the background of treatment was faster on the background of treatment with Tonsilgon N. Increased synthesis of sIgA against the background of Tonsilgon N treatment allows to explain the rapid onset of clinical recovery in patients and to identify an additional mechanism of action of this drug on the local immune response of the oropharyngeal mucosa. It can be assumed that Tonsilgon N is not only pathogenetic, but also immunoregulatory, creating the most effective response of the body to inflammation. Key words: pharyngitis, oropharyngeal mucosa, interleukin-6 (IL-6), secretory immunoglobulin A (sIgA), enzyme-linked immunosorbent assay (ELISA), treatment, Tonsilgon N, sage

Expression of a stress-inducible heme oxygenase-1 in NK cells is maintained in the process of human aging.

Heme oxygenase-1 (HO-1) is a stress-inducible heat shock protein (HSP32) that exerts cytoprotective effects against oxidative stress and inflammation, and is involved in the maintenance of cellular homeostasis. This study aimed to evaluate the expression of HO-1 in natural killer (NK) cells from individuals of different age groups after stimulation with various factors, and to analyze the relationships between the concentration of this cytoprotective protein and parameters corresponding to oxidative stress and inflammation, that is, NOD-like receptor protein 3 (NLRP3), glutathione (GSH), GSH disulfide (GSSG), and interleukin 6 (IL-6). The study population comprised three age groups: young adults (age range, 19-23 years), older adults aged under 85 years (age range, 73-84 years), and older adults aged over 85 years (age range, 85-92 years). NLRP3, GSH, and GSSG concentrations were measured in serum, whereas the HO-1 concentration and IL-6 expression were studied in NK cells cultivated for 48h and stimulated with IL-2, lipopolysaccharide (LPS), or phorbol 12-myristate 13-acetate (PMA) with ionomycin. The analysis of serum NLRP3, GSH, and GSSG concentrations revealed no statistically significant differences among the studied age groups. However, some typical trends of aging were observed, such as a decrease in GSH concentration and an increase in both GSSG level, and GSSG/GSH ratio. The highest basal expression of IL-6 and lowest basal content of HO-1 were found in NK cells of adults over 85 years of age. The NK cells in this age group also showed the highest sensitivity to stimulation with the applied factors. Moreover, statistically significant negative correlations were observed between HO-1 and IL-6 expression levels in the studied NK cells. These results showed that NK cells can express HO-1 at a basal level, which was significantly increased in activated cells, even in the oldest group of adults. The reciprocal relationship between HO-1 and IL-6 expression suggests a negative feedback loop between these parameters.

Down-Regulation of INSR Restores Th17/Treg Immune Balance and Alleviates Airway Hyperviscosity in Asthmatic Mice via Inactivation of STAT3 Pathway.

Allergic asthma (AA) is a prevalent chronic airway inflammation disease. In this study, this study aims to investigate the biological functions and potential regulatory mechanisms of the insulin receptor (INSR) in the progression of AA. BALB/c mice (n = 48) were randomly divided into the following groups: control group, AA group, AA+Lentivirus (Lv)-vector short hairpin RNA (shRNA) group, AA+Lv-vector group, AA+Lv-INSR shRNA group, and AA+Lv-INSR group. The pulmonary index was calculated. mRNA and protein expression levels of INSR, signal transducer and activator of transcription 3 (STAT3), Janus kinase 2 (JAK2), phosphorylated-STAT3 (p-STAT3), phosphorylated-JAK2 (p-JAK2), alpha-smooth muscle actin (α-SMA), febrile neutropenia (FN), mucin 5AC (MUC5AC), and mucin 5B (MUC5B) were examined using reverse-transcription quantitative PCR (RT-qPCR) and western blot assays. Positive expressions of INSR, retinoic acid-related orphan receptor gamma-t (RORγt), and forkhead box protein P3 (Foxp3) were quantified by immunohistochemistry. Fluorescence intensities of α-SMA and FN were detected by immunofluorescence. Pathological morphology was observed through hematoxylin-eosin (H&E) staining, Masson staining, and Periodic Acid-Schiff (PAS) staining. Contents of immunoglobulin E (IgE), interleukin-6 (IL-6), eotaxin, interleukin-4 (IL-4), interleukin-13 (IL-13), interferon-γ (IFN-γ), interleukin-17 (IL-17), and interleukin-10 (IL-10) were quantified using enzyme-linked immunosorbent assay (ELISA). The percentage of T helper 17 (Th17) and regulatory T (Treg) cells was determined through flow cytometry. Compared to the control group, expression levels of INSR, p-STAT3, p-JAK2, α-SMA, FN, MUC5AC, MUC5B, RORγt, and Foxp3, as well as IgE, IL-6, eotaxin, IL-4, IL-13, and IL-17 contents, pulmonary index, glycogen-positive area (%), and Th17 cell percentage significantly increased (p < 0.05). Additionally, pulmonary histopathological deterioration and collagen deposition were aggravated, while Treg cell percentage and IFN-γ and IL-10 contents remarkably decreased (p < 0.05). The overexpression of INSR further exacerbated the progression of allergic asthma, but the down-regulation of INSR reversed the trends of the above indicators. The down-regulation of INSR alleviates airway hyperviscosity, inflammatory infiltration, and airway remodeling, restoring Th17/Treg immune balance in AA mice by inactivating the STAT3 pathway.

The protective role of chemokines 12 and chemokines 4 by mediating interleukin-6 in delayed diabetic foot wound healing

Refractory diabetic foot ulcer is commonly encountered in clinical practice and it is hardly cured with a long duration of treatment and a high expense, as such problem involves multiple disciplines. Therefore, in case of refractory wounds, it is necessary to first analyze the causes, general or local. Immunohistochemistry (IHC) was conducted to determine α-SMA, chemokines 12 (CXCL12) and chemokines 4 (CXCR4) levels in pancreatic tissues and distant normal pancreatic tissues. Cells were treated with recombinant human CXCL12 (rhCXCL12) or the CXCR4 antagonist AMD3100. After treatment, Western blot determined FAK-AKT and ERK1/2 expression in islet cells, whilst ELISA detected the content of IL-6 and IL-8. rhCXCL12 increased the expression and secretion of Interleukin-6 (IL-6) time- and dose-dependently. But the advent of CXCR4 antagonist abrogated the protective effect of rhCXCL12. rhCXCL12 exhibited a protective effect on apoptosis, but this effect was abrogated by down-regulation of IL-6 with AMD3100. In addition, rhCXCL12 increased the phosphorylation of FAK, ERK1/2, AKT, and P38 and inhibition of FAK inhibited IL-6 expression. FAK inhibition almost completely blocked CXCL12-induced activation. This study demonstrates that CXCL12/CXCR4 pathway mediates the expression of IL-6 to enhance healing of refractory diabetic foot wounds by down-regulating the FAK pathway.

The therapeutic effect of phellopterin on colitis-associated cancer and its effects on TLR4/NF-κB pathway and macrophage M2 polarization.

This study was conducted to investigate the effect and mechanism of phellopterin on colitis-associated cancer (CAC). For this purpose, CAC mouse model was established by AOM/DSS method, and the therapeutic effects of phellopterin in different doses were compared. The levels of interleukin-6 (IL-6), IL-1β, IL-10, and tumor necrosis factor-α (TNF-α) in peripheral blood were detected by ELISA. The changes in T lymphocyte subsets and the expressions of CD163, CD206, Arg-1, and Ym-1 in colonic macrophages were detected. The expression of TLR4 and NF-κB p65 in the colon was tested by Western blot. Results showed that as against the Model group, the body weight and survival rate of mice treated with phellopterin were increased, the disease activity index, hematochezia rate, and tumor formation rate were decreased, the colon length was increased, and the number of tumors and spleen index were decreased (P<0.05). As against the Model group, the proportion of CD4+ and CD8+ in the peripheral blood of phellopterin intervention mice increased, the content of IL-6, IL-1β, and TNF-α decreased, and the content of IL-10 increased. The expression of CD163, CD206, Arg-1, and Ym-1 in colonic macrophages was decreased. The protein expressions of TLR4 and NF-κB p65 in colon tissue were decreased (P<0.05). The effect of phellopterin intervention on CAC was dose-dependent. In conclusion, phellopterin can improve the symptoms and inflammatory response of CAC and inhibit the occurrence of colon cancer (CC) by inhibiting M2 polarization of macrophages and activation of the TLR4/NF-κB pathway.

Effects of simvastatin on immunoreaction and inflammation in rats with asthma by regulating NOTCH signaling pathway.

To investigate the effect of simvastatin on the immunoreaction and inflammation in rats with asthma through the NOTCH signaling pathway, a total of 36 Sprague-Dawley (SD) rats were enrolled and randomly divided into the normal group (n=12), model group (n=12) and simvastatin group (n=12). The rats in the normal group were fed normally, those in the model group were prepared into models of asthma, and those in the simvastatin group were prepared into models of asthma and intervened with simvastatin. Next, the morphology of airway tissues was observed via hematoxylin-eosin (HE) staining assay. Besides, immunohistochemistry was employed to determine the expression of interferon-γ (INF-γ), and the relative protein expression levels of NOTCH2 and NOTCH3 were measured by Western blotting (WB). Additionally, enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR) assay were carried out to detect the content of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and the relative mRNA expression levels of INF-γ, IL-6 and TNF-α, respectively. HE staining results uncovered that the airway tissues displayed normal morphology in the normal group and disordered morphology and obvious inflammatory infiltration in the model group. In comparison with the model group, the simvastatin group exhibited significantly improved morphology of airway tissues. Based on immunohistochemistry, the average optical density of INF-γ positive expression was increased in the model group and simvastatin group compared with that in the normal group (P<0.05), and it was distinctly lower in the simvastatin group than that in the model group (P<0.05). The results of WB showed that compared with those in the normal group, the relative protein expression levels of NOTCH2 and NOTCH3 were elevated in model group and simvastatin group (P<0.05), whereas they were overtly reduced in simvastatin group compared with those in model group (P<0.05). It was found through ELISA that the model group and simvastatin group had raised content of IL-6 and TNF-α in comparison with the normal group (P<0.05), while the simvastatin group exhibited markedly decreased content of IL-6 and TNF-α in comparison with the model group (P<0.05). The results of qPCR revealed that the relative mRNA expression levels of INF-γ, IL-6 and TNF-α were distinctly up-regulated in the model group and simvastatin group compared with those in the normal group, displaying statistically significant differences (P<0.05), whereas they were markedly lowered in simvastatin group compared with those in the model group, showing statistically significant differences (P<0.05). Simvastatin represses the immunoreaction and inflammation in rats with asthma by down-regulating the NOTCH signaling pathway.

The Effect of Transfusion and Hypoxia on Cells in an in vitro Model of the Neurovascular Unit

Up to 57% of patients develop postoperative delirium after surgery for congenital heart defects (CHD). To reduce cerebral damage in pediatric patients during CHD surgery it is important to find out what inflicts the worse damage: would it be a systemic inflammatory response (SIR) triggered by transfusion, or hypoxia developed in non-transfused patients? In vitro evaluation of hypoxia and SIR effects on the neurovascular unit (NVU) cells might contribute to finding the answer.The aim of the study was to compare the effect of varying severity hypoxia and SIR on the functional activity of NUV cells in vitro.Materials and methods. An in vitro NVU model was designed including neurons, astrocytes and endotheliocytes. The effect of hypoxia on NVU was evaluated in the control (C) and 4 study groups (H 1–4), formed based on O₂ content in the medium. The C group NVU were cultivated in standard conditions: N₂ — 75%, O₂ — 20%, CO₂ — 5%; H1: N₂ — 99%, O₂ — 1%; H2: N₂ — 98%, O₂ — 2%; H3: N₂ — 97%, O₂ — 3%; H4: N₂ — 96%, O₂ — 4%. The significance of the differences was 0.0125. The effect of interleukin-6 (IL-6) content on NVU was measured by adding to culture medium pediatric patients’ serum with known minimal or maximal SIRS-response. The assessment was made in the Control — an intact NVU model, and 2 study groups — «Minimum» and «Maximum», i. e. samples with minimum or maximum IL-6 content in culture, respectively. The significance of the differences was 0.017. The cells were incubated at a normothermia regimen for 30 minutes. Then, the functional activity of NVU cells was evaluated by measuring transendothelial resistance (TER) for 24 hours and Lucifer Yellow (LY) permeability test at 60 and 90 minutes after the start of the experiment.Results. After incubation under hypoxic conditions, TER changes occurred in all studied groups. However, they were statistically significant only in the group with 1% oxygen content in the medium. TER decrease in this group was observed after 2, 4 and 24 hours. LY permeability also changed at 60 and 90 minutes, similarly — in NVU cultivated with 1% oxygen in the medium. Minimal TER values were documented at 4 hours after patients’ serum was added to NVU cells culture medium, and TER increased at 24 hours in both study groups. Cellular permeability to LY changed significantly after 1 hour exposure in both groups — with minimum and maximum IL-6 content in the medium. Although at 90 minutes, there was no difference between the 3 groups in LY permeability tests.Conclusion. Intensive SIR demonstrated short-term but more deleterious than hypoxia, effect on cells in the NVU model. Hypoxia disrupted functional activity of NUV cells only at 1% O₂ concentration in the medium.

The effect of Dendrobium officinale extract in inhibiting the senescence of H2O2-induced fibroblasts based on the senescence-associated secretory phenotype.

Dendrobium officinale is widely used for a long time in China, with effect of antioxidation, antitumor, enhancing immunity and so on. In recent years, Dendrobium officinale has been gradually used in cosmetics due to its powerful beauty effects. Based on senescence-associated secretory phenotype (SASP), we studied the antiaging effect of Dendrobium officinale extract (DOE) on skin. The senescent model of human skin fibroblasts was established by the induction of H2O2, and the content of SASP factors was tested after the treatment of DOE, such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-1 (MMP-1). It was found that after the treatment with different concentrations of DOE, the contents of IL-6, MCP-1 and MMP-1 all decreased in different degrees. It indicated that DOE could inhibit the secretion of SASP factors and was a promising natural antiaging agent.

Preparation of Multifunctional Seaweed Polysaccharides Derivatives Composite Hydrogel to Protect Ultraviolet B-Induced Photoaging In Vitro and In Vivo.

Seaweed polysaccharides can be used for protective skin photoaging which is caused by long-term exposure to ultraviolet B (UVB). In this study, a multifunctional composite hydrogel (FACP5) is prepared using sulfated galactofucan polysaccharides, alginate oligosaccharides as active ingredients, and polyacrylonitrile modified κ-Carrageenan as substrate. The properties of FACP5 show that it has good water retention, spreadability, and adhesion. The antiphotoaging activity is evaluated in vitro and in vivo. In vitro experiments demonstrate that the components of FACP5 exhibit good biocompatibility, antioxidant, and anti-tyrosinase activities, and could reduce the cell death rate induced by UVB. In vivo experiments demonstrate that, compared with the mice skin in model group, the skin water content treated with FACP5 increases by 29.80%; the thicknesses of epidermis and dermis decrease by 53.56% and 43.98%, respectively; the activities of catalase and superoxide dismutase increase by 1.59 and 0.72 times, respectively; the contents of interleukin-6 and tumor necrosis factor-α decrease by 19.21% and 17.85%, respectively; hydroxyproline content increases by 32.42%; the expression level of matrix metalloproteinase-3 downregulates by 42.80%. These results indicate that FACP5 has skin barrier repairing, antioxidant, anti-inflammatory, and inhibiting collagen degradation activies, FACP5 can be used as a skin protection remedy for photoaging.

Exploring the Mechanism of Chang-An-Kang on Active Ulcerative Colitis Rats Based on NF-κB/STAT3 Signaling Pathway

Objectives The objective of this study was to investigate the therapeutic effect and mechanism of Chang-An-Kang on ulcerative colitis rats. Materials and Methods The rat model of ulcerative colitis induced by 6% glacial acetic acid was established. The corresponding therapeutic drugs were given 24 h after the model was established. The pathological morphology of colon tissue was observed after 21 days of continuous administration. The levels of interleukin-6 (IL-6), interleukin-7 (IL-7), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α) were measured by ELISA kit. The expression levels of NF-κB and STAT3 proteins in colon tissue were detected by IHC. Results The results showed that the changes in the pathological and biochemical indexes of the rat colon tissue indicate that the model was successfully established. Chang-An-Kang could significantly reduce rat colon tissue damage, decrease the content of IL-6, IL-7, and TNF-α, and increase the content of IL-10. The NF-κB and STAT3 protein expression levels were decreased. Conclusion By increasing the content of anti-inflammatory factor IL-10, decreasing the content of pro-inflammatory factors IL-6 and TNF-α, and inhibiting the expression of NF-κB and STAT3 proteins, Chang-An-Kang can reduce inflammatory infiltration. It has an obvious therapeutic effect on acetic acid ulcerative colitis in rats.

Different processed products of Polygonati Rhizoma treat Alzheimer's disease in rats: urine metabolomics based on UPLC-Q/TOF-MS

The study investigated the effects of different processed products of Polygonati Rhizoma(black bean-processed Polygonati Rhizoma, BBPR; stewed Polygonati Rhizoma, SPR) on the urinary metabolites in a rat model of Alzheimer's disease(AD). Sixty SPF-grade male SD rats were randomized into a control group, a model group, a donepezil group, a BBPR group, and a SPR group, with twelve rats in each group. Other groups except the control group were administrated with D-galactose injection(100 mg·kg~(-1)) once a day for seven weeks. The control group was administrated with an equal volume of normal saline once a day for seven consecutive weeks. After three weeks of D-galactose injection, bilateral hippocampal Aβ_(25-35) injections were performed for modeling. The rats were administrated with corresponding drugs(10 mL·kg~(-1)) by gavage since week 2, and the rats in the model and control group with an equal volume of double distilled water once a day for 35 continuous days. The memory behaviour and pathological changes in the hippocampal tissue were observed. The untargeted metabolites in the urine were detected by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS). Principal component analysis(PCA) and orthogonal partial least square-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites and potential biomarkers, for which the metabolic pathway enrichment analysis was conducted. The results indicated that BBPR and SPR increased the new object recognition index, shortened the escape latency, and increased the times of crossing the platform of AD rats in the Morris water maze test. The results of hematoxylin-eosin(HE) staining showed that the cells in the hippocampal tissue of the drug administration groups were closely arranged. Moreover, the drugs reduced the content of interleukin-6(IL-6, P&lt;0.01) and tumor necrosis factor-α(TNF-α) in the hippocampal tissue, which were more obvious in the BBPR group(P&lt;0.05). After screening, 15 potential biomarkers were identified, involving two metabolic pathways: dicoumarol pathway and piroxicam pathway. BBPR and SPR may alleviate AD by regulating the metabolism of dicoumarol and piroxicam.