Interleukin-6 In Group Research Articles

Synergistic antioxidant and anti-inflammatory effects of combined supplementation with oral zinc and dietary Moringa oleifera leaf in streptozotocin-induced diabetic rats

Individual interventions with zinc or M. oleifera leaf powder have shown some promise in managing diabetes-induced oxidative stress and inflammation. This study examined the synergistic effect of oral zinc and dietary M. oleifera leaf supplementation on the serum antioxidant and anti-inflammatory activities in streptozotocin-induced diabetic rats. Seven groups of 56 rats were used in the experiment: (1) normal rats + normal diet, (2) normal rats + 3% M. oleifera leaf-supplemented diet, (3) non-treated diabetic rats, (4) diabetic rats + 200 mg/kg metformin, (5) diabetic rats + 3% M. oleifera leaf-supplemented diet, (6) diabetic rats + 100 mg/kg oral zinc sulfate, and (7) diabetic rats + 3% M. oleifera leaf-supplemented diet + 100 mg/kg oral zinc sulfate. ELISA assay kits were used for antioxidant and anti-inflammatory markers respectively. The results suggest that when all treated diabetic groups were compared with non-treated diabetic control at p<0.05, only groups 4 and 7 showed a significant increase in superoxide dismutase activity. Only group 5 showed a significant increase in reduced glutathione. No significant changes were observed in catalase and the total antioxidant capacity. MDA decreased significantly in group 7 only. There was a significant reduction in interleukin-6 in groups 6 and 7. Only group 7 showed significantly reduced C-reactive protein. Tumor necrosis factor-α reduced significantly in group 6 only. Overall, the combined supplementation with zinc and M. oleifera outperformed the individual treatments with either zinc or M. oleifera in ameliorating diabetes-induced oxidative stress and inflammation, indicating a possible synergistic effect of their combination.

The Efficacy of Topical Formulation Containing Ciplukan (Physalis angulata Linn.) in Modulating Interleukin-17 and Interferon Gamma Expression in Mice (Mus musculus) Psoriasis Model.

Interleukin 17 (IL-17) and interferon gamma (IFN-γ) play a role in the pathogenesis of psoriasis vulgaris (PV). Topical corticosteroids are still utilised as first-line therapy for mild to moderate PV. However, long-term use of corticosteroid is associated with various side effects. Physalis angulata Linn. (Ciplukan) possesses anti-inflammatory properties that could serve as a potential alternative topical therapy for PV. To assess the efficacy of topical ciplukan as an anti-inflammatory agent targeting the expression of IL-17 and IFN-γ. Psoriasis was induced using imiquimod cream, therefore divided into five groups. Group I, the psoriasis control group, received only imiquimod cream. Groups C1 and C2 received imiquimod cream followed by a mixture of Ciplukan and vaseline in a 1:2 and 1:4 ratio, respectively. Group M, the standard therapy group, received imiquimod cream, followed by mometasone furoate cream. Lastly, group V, the vehicle group, received imiquimod cream followed by vaseline album. Expression of IL-17 and IFN-γ in mice's skin tissue was analysed using reverse transcription polymerase chain reaction (RT-PCR) after seven days of treatment. The mean expression of IL-17 in Group C1 (22.60) was significantly lower (p = 0.012) than in the psoriasis control group (23.60), and there was no significant difference (p = 0.613) in Group M (22.41). The mean expression of IFN-γ in Group C1 (26.97) and Group C2 (27.03) was also significantly lower (p = 0.026 and p = 0.026, respectively) than Group I (28.80), and there was no significant difference (p = 0.180 and p = 0.093, respectively) than Group M (26.03). Expression of IL-17 and IFN-γ in the ciplukan group is lower than in the psoriasis control group, and there is no significant difference compared to the standard therapy group.

Retrospective analysis of low-dose interleukin-2 therapy on chronic autoimmune thyroid disease with concurrent systemic lupus erythematosus

Introduction Low-dose interleukin-2 (IL-2) regulates the homeostasis of CD4+ T cells by modulating the proportions of effector and regulatory T cells, thus reducing disease activity in patients with systemic lupus erythematosus (SLE). However, to date, no research has been carried out on the efficacy of low-dose IL-2 for treating autoimmune thyroid disease (AITD). The aim of this study was to observe the effects of IL-2 on AITD patients with concurrent SLE, and explore potential mechanism of action. Methods A retrospective analysis was conducted on 29 SLE patients with concurrent AITD. Among them, 11 patients were in IL-2 therapy group and 18 patients without IL-2 treatment were considered as control group. Two groups had similar disease activities and were treated with comparable regular strategy. Free triiodothyronine (FT3), free thyroxine (FT4), thyroxine(T4), triiodothyronine(T3), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), thyroid peroxidase antibody (TPO-Ab) levels and immune cell subgroups were measured. Results After receiving low-dose IL-2 therapy, the TG-Ab and TPO-Ab levels decreased drastically (TG-Ab p = 0.008, TPO-Ab p = 0.007), and the majority of the AITD patients became seronegative, while there was no discernible change in control group. In IL-2 group, percentage of CD4+ T cells showed a significant increase after treatment (p = 0.029), with an upward trend in the ratio of regulatory T (Treg) cells to follicular helper T (Tfh) cells (Treg/Tfh). The percentage as well as absolute count of B cells demonstrated a decreasing trend. Conclusion Low-dose IL-2 may downregulate the levels of TG-Ab and TPO-Ab by modulating the immune balance of Treg/Tfh and B-cells, providing new avenue for clinical treatment of AITD.

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.

Results of R-CHOP and R-CHOP + interleukin-2 regimens in first-line therapy in patients with diffuse B-cell lymphoma

The study was made to evaluate the effect of interleukin-2 (IL-2) as part of the R-CHOP regimen on the rate of a complete metabolic response (CMR) using the data of interim positron emission tomography (PET/CT) and progression-free survival compared to the standard regimen in patients with diffuse B-cell lymphoma (DCLC). The data of 152 patients with biopsy-proven DCLC who were treated in the period 2015–2020 were included. Among them, 59 patients were included in the prospective group (R-CHOP + IL-2 in a total course dose of 5,000,000 IU). The control group consisting of 93 patients received standard R-CHOP therapy. PET/CT was performed after 4 courses of therapy, metabolic response was assessed using the Deauville scale, and Deauville 1-2 was classified as CMR. The rate of CMR in the R-CHOP+IL-2 group was 67.8 %, while in the control group it was 50.5 % (pχ² = 0.044). The 5-year progression-free survival (PFS) in the R-CHOP+IL-2 and R-CHOP groups was 80.7 and 64.5 %, respectively (p = 0.04). In the favorable and intermediate prognosis groups (IPI 0–3), PFS was not statistically significantly different depending on treatment. At high risk (IPI 4–5), the 5-year PFS in the R-CHOP + IL-2 and R-CHOP groups was 71.4 and 25.0 %, respectively (p = 0.02). Including IL-2 in the R-CHOP regimen in the first-line treatment of patients with DCLC increases the incidence of CMR according to 18-FDG PET/CT after 4 courses of chemoimmunotherapy and PFS in the high-risk group.

Promoting repair of highly purified stromal vascular fraction gel combined with advanced platelet-rich fibrin extract for irradiated skin and soft tissue injury.

BackgroundTo evaluate the effect of highly purified stromal vascular fraction gel (SVFG) combined with advanced platelet-rich fibrin extract (APRFE) in treatment of irradiated skin and soft tissue injury.MethodsThe subcutaneous fat and whole blood of 4 rabbits were collected to isolate the SVFG and APRFE, respectively. Forty-eight rabbits were divided into 4 groups to prepare irradiated skin injury models with 25 Gy for 24 hours; corresponding dose were performed subcutaneously injected into wounds. In group A, the rabbits were treated with 0.3 mL APRFE combined with 1 mL SVFG. In group B, the rabbits were treated with 1 mL SVFG. In group C, the rabbits were treated with 0.3 mL APRFE, and group D was treated with 1 mL normal saline. The wound healing was detected on the 2, 5, 9 and 14 d after intervention. The wounds tissue was cut for hematoxylin and eosin (HE) staining to observe the structure and Masson staining to observe the collagen content. The expression of CD31 in each group was detected by immunohistochemistry (IHC), the protein and mRNA levels of K19, hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), interleukin 8 (IL-8) and interleukin 10 (IL-10) were detected respectively by Western blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) on 7, 14 and 28 d after intervention.ResultsIt is revealed that wound healing rates from 5 to 14 d in group A was significantly higher than that of control. The wounds healing rates in group B and C were significantly higher than that of control after 12 d. Masson staining results showed that the collagen content in group A was significantly higher than that of the other 3 groups on the 7, 14 and 28 d. The results of IHC showed that the expression of CD31 in group A was significantly higher than that of the other 3 groups on 7, 14 and 28 d. WB and RT-PCR results showed that relative expression levels of K19, HIF-1α, VEGF, IL-10 in group A were significantly higher than that of the other 3 groups on 7, 14 and 28 d. However, the relative expression levels of IL-8 in group A was significantly lower than that of the other 3 groups on 7, 14 and 28 d.ConclusionsSVFG combined with APRFE can promote the repair of irradiated skin and soft tissue injury by accelerating angiogenesis, promoting collagen synthesis and reducing inflammation.

Boric Acid Solution Inhibits Candida albicans Infections in Mouse Skin via the IL-23/Th17 Axis.

The purpose of this study was to investigate the effect and mechanism of 3% boric acid solution (BAS) against Candida albicans (CA) infection via the interleukin-23 (IL-23)/T helper 17 cell (Th17) axis. 36 female mice were randomly divided into 3 groups, and 2 injection sites on the back of the mice were chosen at random. Group N was injected with sterile water for injection (SWFI), and Group M and Group B were injected with CA mycelium suspension. After successful model verification, the remaining mice entered the following treatments 5 days later. Group B was treated with 3% BAS, Group M was treated with SWFI, and Group N was not treated. Levels of interleukin-17 (IL-17), IL-22, and IL-23 in mouse blood were measured on days 1, 3, 5, and 7 of treatment. On day 7, IL-17, IL-22, and IL-23 in mouse skin were detected. Serum levels of IL-17, IL-22, and IL-23 in Group M were higher than in Group N on the first day of treatment (p < 0.05). Expression levels of IL-17, IL-22, and IL-23 in the epidermis of the skin lesions in Group M were higher than in Group N on day 7 (p < 0.05). The serum level of IL-17 in Group B was higher than in Group M on days 5 and 7 (p < 0.05). Serum levels of IL-22 in Group B on days 1, 5, and 7 were higher than in Group M (p < 0.05). Serum levels of IL-23 in Group B were higher than in Group M on days 3, 5, and 7 (p < 0.05). IL-17 and IL-23 in Group B reached a peak on day 5, significantly different on days 1, 3, and 7 (p < 0.05). The expression intensity of IL-17, IL-22, and IL-23 in the skin lesions of Group B was higher than that of Group M on day 7 (p < 0.05). We conclude that IL-17, IL-22, and IL-23 are involved in the anti-CA activity in mouse skin, and 3% BAS increased IL-17, IL-22, and IL-23 to mediate these effects.

Low-dose cyclophosphamide combined with IL-2 inhibits tumor growth by decreasing regulatory T cells and increasing CD8+ T cells and natural killer cells in mice

Interleukin-2 (IL-2) benefits some cancer patients by promoting the proliferation of cytotoxic effector T cells, but this process is limited by the expansion of regulatory T cells (Tregs). Low-dose cyclophosphamide (CTX) can inhibit the number and function of Tregs. We treated carcinoma-bearing mice with Vehicle, CTX, IL-2 and CTX + IL-2 to investigate the effects of low-dose CTX combined with IL-2 in antitumor treatment. In comparison to monotherapy, CTX + IL-2 significantly limited tumor growth, via tumor cell proliferation inhibition and increased apoptosis. The infiltration of CD8+ T cells in tumor tissues was significantly increased in the CTX + IL-2 group. CTX + IL-2 safely increased CD8+ T and natural killer cells in the spleen, lymph nodes and peripheral blood, and CTX attenuated the increase in Tregs induced by IL-2 in the spleen.

Effects of interleukin-17 antibody on polarization of macrophages in adipose tissue of high-fat diet fed mice exposed to bisphenol A

To investigate the effects of interleukin-17(IL-17) antibody on polarization of adipose tissue macrophages(ATM) in mice fed with high-fat diet(HFD) exposed to bisphenol A(BPA). Four week-old male C57 BL/6 mice were divided into control group, IgG group, IL-17 antibody group, 1000 nmol/L BPA group, 1000 nmol/L BPA+IgG group, and 1000 nmol/L BPA+IL-17 antibody group according to random number table method. Eight mice per group were fed with HFD and BPA was exposed by drinking water. The IgG group and the 1000 nmol/L BPA+IgG group were intraperitoneally injected with 100 μg IgG antibody once a week, and the IL-17 group and the 1000 nmol/L BPA+IL-17 antibody group were intraperitoneally injected with 100 μg IL-17 antibody once a week. After 16 weeks, the mice were sacrificed, and serum samples were collected for serum separation. Leptin level was measured by enzyme-linked immunosorbent assay(ELISA). The expression of IL-1β, IL-6 and monocyte chemoattractant protein-1(MCP-1)inflammatory cytokines were observed by immunohistochemistry(IHC) of adipose tissue of epididymis. The activity of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)was measured by ELISA, and the proportion of M1 and M2 ATMs was measured by flow cytometry(FCM). The expression of CD11 c and CD206 mRNA was measured by qRT-PCR. Compared with the control group, serum leptin, the expressions of inflammatory cytokines IL-6, IL-1β and MCP-1 in adipose tissue were increased in 1000 nmol/L BPA group, the proportion of M1 type ATM was increased(22.000%±0.500% vs. 31.467%±0.379%), iNOS activity was increased, CD11 c mRNA expression was increased, Arg-1 activity was decreased, CD206 mRNA expression was decreased, the differences were statistically significant(P&lt;0.05), but the proportion of M2 type ATM was decreased insignificantly(P&gt;0.05). There was no significant change in IgG group. Compared with 1000 nmol/L BPA group, IgG+1000 nmol/L BPA group had no significant change. In 1000 nmol/L BPA+IL-17 antibody group, serum leptin was decreased, the expressions of inflammatory factors IL-6, IL-1β and MCP-1 in adipose tissue were down-regulated, and the proportion of M1 type ATM was decreased(31.467%±0.379% vs. 22.933%±0.153%), iNOS activity was decreased, CD11 c mRNA expression was decreased, and the proportion of M2 type ATM was increased(4.847%±0.655% vs. 7.840%±0.555%), Arg-1 activity was enhanced, and CD206 mRNA expression was up-regulated, the differences were statistically significant(P&lt;0.05). IL-17 antibody may reduce the secretion of ATM inflammatory factors by inhibiting the polarization of ATM to M1 type, thus improving the inflammation of adipose tissue in BPA-infected HFD-fed mice.

Melatonin receptor 2 mediated spinal dorsal horn astrocytes IL-17 inhibition contributes to electroacupuncture analgesia in neuropathic pain rats

To investigate the effect of electroacupuncture (EA) on pain behaviors and expression of spinal dorsal horn melatonin receptor 2 (MT2) and interleukin-17 (IL-17) in neuropathic pain rats, so as to explore its mechanism underlying pain relief. The present study includes 3 parts. In the first part, eighteen male SD rats were randomly divided into 3 groups: sham operation, model and EA groups, with 6 rats in each group. The neuropathic pain model was established by chronic constriction injury (CCI) of the right sciatic nerve. On the 7th day following modeling, EA was applied to the right "Zusanli" (ST36) and "Sanyinjiao" (SP6) (1 mA,2 Hz/100 Hz) for 30 min. The mechanical pain threshold(MWT) and thermal pain thre-shold(TPT) of the affected limb were detected before modeling, 7 days following modeling and 60 min after EA. The expression of MT2 in spinal dorsal horn was detected by Western blot. The contents of melatonin （Mel） and IL-17 in the spinal dorsal horn were determined by ELISA. The expression of glial fibrillary acidic protein (GFAP) in the spinal dorsal horn was determined by Western blot and immunohistochemistry. In the second part, 30 rats were divided into 5 groups: sham operation, model, EA, MT2 antagonist (4-P-PDOT), and dimethyl sulfoxide (DMSO) groups, with 6 rats in each group. Rats of the 4-P-PDOT and DMSO groups were intrathecal injection with 10 μL MT2 antagonist 4-P-PDOT (100 μg) and equivalent DMSO 30 min before EA. The MWT and TPT of affected limb were detected. The GFAP expression and IL-17 content in the spinal dorsal horn was detected by Western blot， immunohistochemistry and ELISA, respectively. In the third part, 30 rats were randomly divided into 5 groups: sham operation, model, EA, recombinant IL-17, and normal saline groups, with 6 rats in each group. The recombinant IL-17 protein (100 ng, 10 μL) and the same amount of 0.9% sodium chloride solution were intrathecal injection into the rats of the recombinant IL-17 group and the normal saline group 30 min before the EA. The MWT and TPT of affected limb were measured. On the 7th day after modeling, the MWT of rats in the model group and the EA group were significantly higher, while TPT were lower than those before the modeling (P<0.05). At 60 min after EA, compared with the model group, the MWT and TPT of the EA group reversed significantly (P<0.05). The levels of GFAP and IL-17 were significantly increased, while the levels of Mel and MT2 were significantly decreased in the model group than in the sham operation group (P<0.05), and those were considerably reversed in the EA group than in the model group (P<0.05). Compared with the EA and DMSO groups, the MWT in the 4-P-PDOT group were significantly increased, while TPT were decreased (P<0.05), and the contents of GFAP and IL-17 were significantly increased (P<0.05). Compared to the EA and normal saline groups, MWT of the rats in the recombinant IL-17 group were significantly increased, while TPT decreased (P<0.05). EA of ST36 and SP6 can alleviate neuropathic pain in CCI rats, which is closely related to its effect in inhibiting the release of IL-17 from astrocytes mediated by MT2.

Estimating Pulmonary Function, Interleukin-6 (IL-6), And Superoxide Dismutase-3 (EC-SOD3) Levels in Patients with Chronic Bronchial Asthma on Curcumin Adjuvant Therapy

This study was designed to evaluate the effectiveness of curcumin supplement as antioxidant and anti-inflammatory in patients with chronic bronchial asthma. Forty patients diagnosed with chronic bronchial asthma were enrolled in this study and allocated into group (1) patients assigned to receive conventional therapy of asthma, and group (2) patient assigned to receive conventional therapy of asthma combined with 750 mg curcumin supplement twice daily for two months. Pulmonary function test, asthma control test, serum interleukin-6 and serum extracellular super oxide dismutase 3 were measured before and after two months in both study groups. After two months, the mean values of pulmonary function test (spirometry) and asthma control score showed significant increase compared to pre-treatment values in group 2 patients (P&lt;0.01). Moreover, there was marked decrease in the level of interleukin-6 in group 2 patients after two months (p&lt; 0.05) compared to the increased in group 1 patients. The mean level of super oxide dismutase 3 didn’t show any increase in both study groups after treatment. Curcumin supplement produced improvement in pulmonary function of patients with chronic bronchial asthma along with the reduction in inflammatory status. No change in endogenous oxidative status after curcumin supplementation.

The Efficacy of Combined Medication With Methylprednisolone and Erythropoietin in the Treatment of Ischemia-Reperfusion Injury to the Spinal Cord in Patients With Cervical Spondylotic Myelopathy.

IntroductionCervical myelopathy (CM) is caused by degenerative or congenital changes in the discs and soft tissues of the cervical spine, leading to chronic compression of the spinal cord. The current treatment for moderate-to-severe CM is surgical decompression, which is effective in most cases; however, it can cause inflammation of the nervous system and spinal cord reperfusion injury, resulting in perioperative neurological complications and suboptimal neurological recovery. The aim of this study was to investigate the therapeutic effects of the combination of erythropoietin and methylprednisolone in the treatment of ischemia-reperfusion injury to the spinal cord and to analyze its effects on the levels of interleukin-1 beta (IL-1β), interleukin-1 receptor antagonist (IL-1RA), and interleukin-8 (IL-8).Materials and methodsThis study included 110 patients admitted to the hospital due to cervical spondylotic myelopathy. They were randomized into two groups of 55 patients each: a control and an observation group. In both groups of patients, fusion internal fixation and anterior cervical discectomy were performed. The difference, however, was that the control group received a rapid intravenous injection of 30 mg/kg methylprednisolone 30 minutes prior to spinal cord decompression, while the observation group received an intravenous injection of 30 mg/kg methylprednisolone and 3,000 U/kg erythropoietin 30 minutes before spinal cord decompression. The study was approved by the Hospital Ethical Committee of the Dow University of Health Sciences, Karachi. The neurological function of both groups of patients was assessed before the procedure and three months after the treatment using the Japanese Orthopedic Association (JOA) method of assessing spinal cord function (40-point rating method). Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of neuron-specific enolase (NSE), S-100β, IL-1RA, IL-1β, and IL-8 in both groups. The quality of life of patients in both groups was assessed three months after the treatment with the World Health Organization Quality of Life assessment instrument (WHOQOL-100).ResultsBefore the treatment, there was no significant variance between the two groups in the JOA score and the 40-point rating method. Similarly, there was no significant difference in the levels of IL-1β, IL-1RA, and IL-8 between the two groups (p-value = 0.262, 0.387, and 0.154 respectively) prior to the treatment. Three months after the treatment, the levels of IL-1β and IL-8 in the observation group were 21.83 ±3.65 ng/l and 357.07 ±32.36 ng/l respectively, both lower than the control group value (p-value = 0.026, 0.028 respectively). The level of IL-1RA in follow-up was 21.59 ±1.15 ng/l, which was higher than that in the control group. Three months after the treatment, all the WHOQOL-100 parameters of the observation group for psychology, physiology, social relations, independence, spirituality, environment, and general quality of life were higher than those of the control group; the variance among the groups was statistically significant (p-value: <0.001).ConclusionsThe combination therapy with erythropoietin and methylprednisolone is effective for ischemia-reperfusion injuries of the spinal cord. It also reduces S-100β and NSE, inhibits IL-1β, and increases IL-8 and IL-1RA. Therefore, it preserves and improves spinal nerve function and the quality of life of patients.

Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility.

Background: The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Cai) handling and VA susceptibility by IL-17.Methods: The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, N = 6) and the IL-17 with neutralizer (0.4 μg/ml, N = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Cai transient duration (CaiTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed.Results: There were longer APD80, CaiTD80 and increased thresholds of APD and CaiTD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na+/Ca2+ exchanger, phospholamban, and ryanodine receptor Ca2+ release channel were upregulated, and the subunit of L-type Ca2+ current and sarcoplasmic reticulum Ca2+-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group.Conclusions: IL-17 enhanced CaiTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.

Application of different kinds of endotracheal intubation in the combined thoracoscopic and laparoscopic esophagectomy

Objective: To observe the application of three different kinds of endotracheal intubation in the combined thoracoscopic and laparoscopic esophagectomy. Methods: one hundred and eighty patients undergoing combined thoracoscopic and laparoscopic esophagectomy under general anesthesia from the Affiliated Cancer Hospital of Zhengzhou University from February to September 2019 were randomly divided into three groups which include: double-lumen endotracheal intubation group (group S,n=60),single-lumen endotracheal intubation group (group D,n=60) and Coopdech occlusion of bronchial catheter combined with a single-lumen endotracheal intubation group (group C,n=60). The arterial blood samples were collected immediately after endotracheal intubation (T0), 30 min after artificial pneumothorax (single lung ventilation) (T1), 30 min after artificial pneumothorax (double lung ventilation) (T2), and 30 min after extubation (T3) to detect arterial blood gas. Patients' heart rate (HR), blood oxygen partial pressure (PaO2), blood carbon dioxide partial pressure (PaCO2) and airway pressure(Paw) were recorded at T0-T3.Completion time of endotracheal intubation, carbon dioxide intrathoracic inflation pressure, degree of lung collapse and incidence of postoperative 3-day pneumonia in three groups were recorded. The bronchoalveolar lavage fluid (BALF) of patients at T0, T2 and the end of the operation (T4) were collected to detect the levels of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) in BALF by enzyme-linked immunosorbent assay (ELISA). Results: A total of 14 patients were excluded during the operation, of which 9 cases lasted longer than 6 hours, 3 cases had arrhythmia during the operation and 2 cases lasted less than 1 hour. Finally, 56 cases in group S, 54 cases in group D and 56 cases in group C completed the experiment. The satisfaction rates of lung collapse in group S, group D and group C were 85.7% (48/56), 100.0% (54/54), 89.2% (50/56), respectively, with no statistically significant difference (χ²=1.308, P>0.05). The intrathoracic inflation pressure of carbon dioxide in group D was (10.2±2.2) mmHg (1 mmHg=0.133 kPa), which was higher than (5.1±3.4) mmHg in group S and (5.6±3.1) mmHg in group C, the difference was statistically significant (F=-9.303, P<0.05). The incidence of postoperative 3-day pneumonia in group D was 14.8%, which was lower than 39.3% in group S and 17.8% in group C, the difference was statistically significant (χ²=8.300, P<0.05). At T4, the value of TNF-α in group D was (122.4±4.4) ng/L, which was lower than that in group S and group C, (257.9±6.3) and (185.8±5.6) ng/L, with statistically significant difference (F=69.020, P<0.05). At T4, the value of IL-6 in group D was (175.4±4.9) ng/L, which was lower than that of patients in group S and group C, (289.6±6.8) and (226.2±4.4) ng/L, with statistically significant difference (F=59.750, P<0.05). At T4, the value of IL-8 in group D was (303.1±7.2) ng/L, which was lower than in group S and group C, (595.4±22.1) and (436.8±10.9) ng/L, with statistically significant difference (F=55.359, P<0.05). Conclusion: All the three endotracheal intubations can produce satisfactory ventilation effect in the combined thoracoscopic and laparoscopic esophagectomy, however, single-lumen endotracheal intubation has less effect on lung injury.

Probiotics on Intestinal Flora Disturbance and Bacterial Translocation in Mice with Inflammatory Bowel Disease

Inflammatory bowel disease is becoming more and more common in western countries and less common in China. However, with the change of dietary structure, the incidence of inflammatory bowel disease is also increasing in China. It will cause abdominal pain, diarrhea and mucus, pus and blood, which are repeatedly delayed and difficult to alleviate. To explore the effectiveness of probiotics in the treatment of inflammatory bowel disease, Lactobacillus plantarum in probiotics and fifteen 8 w old female mice were selected for the experiment. We divided the mice into three groups: blank control group, interleukin-10 group and interleukin-10+Lactobacillus plantarum group. The interleukin-10+Lactobacillus plantarum group was gavaged with 0.5 ml of Lactobacillus plantarum bacterial solution (1.0×109 CFU/ml) every d. The blank control group and interleukin-10 group were gavaged with 0.5 ml of Ringer buffer for 4 consecutive w and compared the changes caused by Lactobacillus plantarum on Bifidobacterium, Lactobacillus, Clostridium perfringens and Enterobacter in the intestinal flora of mice and the changes caused by Lactobacillus plantarum on the intestinal flora effect of bacterial translocation in membranous lymph nodes and spleen. We found that the content of Enterobacter in the blank control group was the lowest at all three time points, with an average of 6. The content of Enterobacter in the interleukin-10+Lactobacillus plantarum group and the interleukin-10 group was 6.5 and 6.6 respectively, at the beginning of 0 w and 6.3 at the beginning of 2 w but after the 4 w, the content of Enterobacter in the two groups became 6.4 and 6.7, the difference increasedy.

IL-17 promotes proliferation, inflammation and inhibits apoptosis of HaCaT cells via interacting with the TRAF3 interacting protein 2.

The present study aimed to investigate the effects of interleukin-17 (IL-17) on the function of keratinocytes and to further investigate its associated mechanism. Human immortalized epidermal cells (HaCaT) were divided into sham control group (Sham), TRAF3 interacting protein 2 (TRAF3IP2)-knockdown with lentivirus group (si-TRAF3IP2), sham control+IL-17 group (Sham+IL-17) and TRAF3IP2-knockdown with lentivirus+IL-17 group (si-TRAF3IP2+IL-17). MTT and flow cytometry assays demonstrated that IL-17 promoted proliferation and inhibited apoptosis of HaCaT cells, while this effect was reversed following knockdown of TRAF3IP2 with lentiviral vectors. In addition, a marked increase in the levels of IL-6, IL-8, IL-23, TNF-α and VEGF was observed in the Sham+IL-17 group compared with that noted in the Sham group (P<0.05). Furthermore, reverse transcription-quantitative polymerase chain reaction and western blotting indicated that the mRNA and protein expression levels of caspase-3 in the si-TRAF3IP2+IL-17 group were significantly increased compared with those of the Sham+IL-17 group (P<0.05). Taken together, the results indicated that IL-17 promoted proliferation and inflammation and inhibited apoptosis of HaCaT cells by interacting with the TRAF3IP2 adaptor protein, while knockdown of the expression of TRAF3IP2 reduced the effects of IL-17 in HaCaT cells.

Effects of Different Routes in PMSC Transfusion on the Levels of Hematopoietic Regulatory Factors in Aplastic Anemia Rats

To investigate the effects of different routes in placental mesenchymal stem cells (PMSC) on serum expression levels of IL-4, IL-17, TNF-α and IFN-γ in aplastic anemia (AA) rats. The rat model of aplastic anemia (AA rats) was established by 5-fluorouracil combined with busulfan. The rats was divided into four groups: control, experimental, PMSC-injected into the tail vein, and PMSC-injected into the medullary cavity. The general state of rats in each group was observed in detail before and after treatment. The serum levels of interleukin-4 (IL-4) , interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA) at week 1, 3 and 5 after treatment. The serum levels of TNF-α, IFN-γ and IL-17 in the experimental group were significantly higher than those in the control group, while the level of IL-4 was significantly decreased (P＜0.05). The levels of TNF-α, IFN-γ and IL-17 gradually decreased after treatment while the level of IL-4 increased. By the fifth week, the above indexes were closed to the control group (P＞0.05), and the levels of TNF-α, IFN-γ and IL-17 in the group with PMSCs injected via the medullary cavity decrease more significantly than those group with PMSC injected via the tail vein, but level of IL-4 was not significantly different between two groups. The level of serum hematopoietic negative regulators increase significantly, and the level of hematopoietic promoting factors decreases significantly in aplastic anemia rats. PMSC can down-regulate the level of hematopoietic negative regulators and up-regulate the level of hematopoietic promoting factors in the rats with aplastic anemia, and the inhibition of hematopoietic negative regulators by intramedullary injection is more significant than that by caudal vein injection.

Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma

BackgroundA pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We...

Effects and mechanism of interleukin-17-modified mouse bone marrow mesenchymal stem cells on rejection reaction of allogeneic skin transplantation in mice

Effects and mechanism of interleukin-17-modified mouse bone marrow mesenchymal stem cells on rejection reaction of allogeneic skin transplantation in mice

Immune checkpoint inhibitors (ICI) in clear cell renal cell carcinoma (ccRCC) following high-dose interleukin-2 (IL-2).

635 Background: IL-2 can be curative in a small subset of ccRCC patients (pts). Recent data suggest that ICIs may lead to long lasting responses, and ICI therapy following progression on IL-2 seems reasonable. However, data regarding the safety and efficacy of ICI following IL-2 is limited. Methods: ccRCC pts treated with ICI after first line were identified at UT Southwestern Medical Center from 2014 – 2018 and assessed by comparison to IL-2 naïve pts at the time of ICI initiation. Outcomes included objective response rates (ORR) determined by RECIST v1.1, time to next treatment (TNT) and overall survival (OS). Immune-related adverse events (irAEs) were graded per CTCAE v4.0. Comparisons were performed using Pearson Chi-square, independent t-tests, and Fischer’s exact tests as appropriate. The log-rank test was utilized for Kaplan-Meier survival analyses. Results: We identified 127 ccRCC pts treated with ICI after first line, 17.3% (22) who had received prior IL-2 and 83.7% (105) who were IL-2 naïve. Pts in the IL-2 group were younger (mean age, 56 vs. 63 years; p=0.003), and more heavily pretreated (median 2 prior lines vs. 1; p &lt;0.0001). The distribution by IMDC criteria was similar with 86.4% (19) and 76.4% (81) in intermediate/ poor group in IL-2 vs. IL-2 naïve groups, respectively (p = 0.431). The ORR was 9.1% (2/22) vs. 21.2% (22/104) in the IL-2 vs. IL-2 naïve groups, respectively (p=0.244). The median TNT was 7.5 (95% CI: 1.8 to 13.2) vs. 9.2 (95% CI: 6.0 – 12.4; p= 0.667) months in the IL-2 vs. IL-2 naïve groups, respectively. The median OS was 26.4 (95% CI: 17.3 – 35.5) vs. 29.8 (23.1 to 36.4) months in the IL-2 vs. IL-2 naïve group, respectively. 18.2% (4) vs. 21.9% (23) pts developed a grade 3/4 irAE in the IL-2 vs. IL-2 naïve group, respectively (p=0.698). Conclusions: Our study suggests that ICI therapy following treatment with high-dose IL-2 remains efficacious and is not associated with an increased risk of irAEs.