Concentrations Of IL-1β Research Articles

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.

Bone mesenchymal stem cell-derived exosomal miR-26a-3p promotes autophagy to attenuate LPS-induced apoptosis and inflammation in pulmonary microvascular endothelial cells.

Acute lung injury (ALI) is a serious lung disease. The apoptosis and inflammation of pulmonary microvascular endothelial cells (PMVECs) are the primary reasons for ALI. This study aimed to explore the treatment effect and regulatory mechanism of bone mesenchymal stem cell-derived exosomes (BMSC-expos) on ALI. PMVECs were stimulated by Lipopolysaccharide (LPS) to imitate ALI environment. Cell viability was determined by CCK-8 assay. Cell apoptosis was evaluated by TUNEL and flow cytometry. ELISA was utilized for testing the contents of TNF-α, IL-1β, IL-6, and IL-17. Western blot was applied for testing the levels of autophagy-related proteins LC3, p62, and Beclin-1. RNA interaction was determined by luciferase reporter assay. The ALI rat model was established by intratracheal injection of LPS. Evans blue staining was utilized for detecting pulmonary vascular permeability. Our results showed that LPS stimulation notably reduced cell viability, increased cell apoptosis rate, and enhanced the contents of inflammatory factors in PMVECs. However, BMSC-exo treatment significantly abolished the promoting effects of LPS on cell injury. In addition, we discovered that BMSC-exo treatment notably activated autophagy in LPS-induced PMVECs. Furthermore, BMSC-expos upregulated miR-26a-3p expression and downregulated PTEN in PMVECs. MiR-26a-3p was directly bound to PTEN. MiR-26a-3p overexpression reduced cell apoptosis, and inflammation and promoted autophagy by silencing PTEN. Animal experiments proved that miR-26a-3p overexpression effectively improved LPS-induced lung injury in rats. The results proved that BMSC-expos promotes autophagy to attenuate LPS-induced apoptosis and inflammation in pulmonary microvascular endothelial cells via miR-26a-3p/PTEN axis.

Progesterone induces neuroprotection associated with immune/inflammatory modulation in experimental traumatic brain injury.

An imbalance of immune/inflammatory reactions aggravates secondary brain injury after traumatic brain injury (TBI) and can deteriorate clinical prognosis. So far, not enough therapeutic avenues have been found to prevent such an imbalance in the clinical setting. Progesterone has been shown to regulate immune/inflammatory reactions in many diseases and conveys a potential protective role in TBI. This study was designed to investigate the neuroprotective effects of progesterone associated with immune/inflammatory modulation in experimental TBI. A TBI model in adult male C57BL/6J mice was created using a controlled contusion instrument. After injury, the mice received consecutive progesterone therapy (8 mg/kg per day, i.p.) until euthanized. Neurological deficits were assessed via Morris water maze test. Brain edema was measured via the dry-wet weight method. Immunohistochemical staining and flow cytometry were used to examine the numbers of immune/inflammatory cells, including IBA-1 + microglia, myeloperoxidase + neutrophils, and regulatory T cells (Tregs). ELISA was used to detect the concentrations of IL-1β, TNF-α, IL-10, and TGF-β. Our data showed that progesterone therapy significantly improved neurological deficits and brain edema in experimental TBI, remarkably increased regulatory T cell numbers in the spleen, and dramatically reduced the activation and infiltration of inflammatory cells (microglia and neutrophils) in injured brain tissue. In addition, progesterone therapy decreased the expression of the pro-inflammatory cytokines IL-1β and TNF-α but increased the expression of the anti-inflammatory cytokine IL-10 after TBI. These findings suggest that progesterone administration could be used to regulate immune/inflammatory reactions and improve outcomes in TBI.

Associations between Th1-related cytokines and complicated pediatric appendicitis

The pathogenesis of appendicitis is not understood fully, and the diagnosis can be challenging. Previous research has suggested an association between a T helper (Th) 1-dependent immune response and complicated appendicitis. This prospective cohort study aimed to evaluate the association between serum concentrations of the Th1-associated cytokines interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-10, IL-17A and tumor necrosis factor beta (TNF-β) and the risk of complicated appendicitis in children. Appendicitis severity was determined through histopathological examination. A total of 137 children < 15 years with appendicitis were included with a median age of 10 years (IQR 8–12); 86 (63%) were boys, and 58 (42%) had complicated appendicitis. Children with complicated appendicitis had significantly higher concentrations of serum IL-6 and IL-10, and lower of TNF-β. After adjustment for age, symptom duration, and presence of appendicolith in a multivariable logistic regression, a higher concentration of IL-6 remained associated with an increased risk of complicated appendicitis (aOR 1.001 [95% CI 1.000–1.002], p = 0.02). Serum concentrations of IL-1α, IL-1β, IL-2, IL-10, IL-17A and TNF-β were not significantly associated with the risk of complicated appendicitis. In conclusion, our results suggests that the systemic inflammatory response in complicated appendicitis is complex and not solely Th1-dependent.

Effect of electroacupuncture on neuronal programmed necrosis by regulating RIP1/RIP3/MLKL pathway in rats with cerebral ischemia reperfusion injury.

To investigate the neuroprotective effect of electroacupuncture (EA) at "Quchi"(LI11) and "Zusanli"(ST36) in the rats with cerebral ischemia reperfusion injury and its influence on programmed necrosis of cerebral cortical neurons. Sixty male SD rats were randomly divided into sham-operation group, model group, EA group and inhibitor group, with 15 rats in each group. Left middle cerebral artery occlusion model was established using the modified thread embolism method. In the sham-operation group, the carotid artery was exposed and dissociated in each rat. EA was applied to "Quchi"(LI11) and "Zusanli"(ST36) on the right side for 30 min each time, once daily for 7 days in the rats of the EA group. The rats in the inhibitor group were intraperitoneally injected with norstatin-1 (0.6 mg/kg) for consecutive 7 days. The neurological deficit score of rats in each group was observed. HE staining was adopted to detect the degree of pathological damage of the cerebral cortex in the infarction area. Using TUNEL staining, the apoptosis of cortical neurons in the infarction area was determined；the contents of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 were detected by ELISA；the mRNA and protein expression of the receptor interacting protein-1 (RIP1), the receptor interacting protein-3 (RIP3) and the substrate mixed lineage kinase like protein (MLKL) were detected by fluorescence quantitative PCR and Western blot, respectively. In comparison with the sham-operation group, the neurological deficit score in the model group was higher(P<0.01)；HE staining showed that there was the pathological damage in the infarction area；the neuron apoptosis rate, the contents of TNF-α, IL-1β and IL-6, and the mRNA and protein expressions of RIP1, RIP3 and MLKL increased(P<0.01) in the model group. In the EA group, the neurological deficit score was reduced(P<0.01)；HE staining showed that the pathological damage was ameliorated in the infarction area；the neuron apoptosis rate, the contents of TNF-α, IL-1β and IL-6, and the mRNA and protein expressions of RIP1, RIP3, MLKL decreased(P<0.05, P<0.01) when compared with those in the model group. EA can attenuate cerebral ischemia reperfusion injury and display its neuroprotective effect probably through inhibiting programmed necrosis of cerebral cortical neurons in the rats.

Inhibiting apoptosis and GSDME-mediated pyroptosis attenuates hepatic injury in septic mice

BackgroundSepsis is characterized by severe inflammation and organ dysfunction resulting from a dysregulated organismal response to infection. Although pyroptosis has been presumably shown to be a major cause of multiple organ failure and septic death, whether gasdermin E (GSDME)-mediated pyroptosis occurs in septic liver injury and whether inhibiting apoptosis and GSDME-mediated pyroptosis can attenuate septic liver injury remain unclear. This study investigated the role of apoptosis and GSDME-mediated pyroptosis in septic liver injury. MethodsAdult male C57BL/6 mice were randomly divided into four groups: sham, cecal ligation puncture (CLP), CLP + Z-DEVD-FMK (a caspase-3 inhibitor, 5 mg/kg), and CLP + Ac-DMLD-CMK (a GSDME inhibitor, 5 mg/kg). Sepsis severity was assessed using the murine sepsis score (MSS). Hepatic tissue damage was observed by the hematoxylin-eosin staining method, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the levels of malondialdehyde (MDA), the concentrations of interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were measured according to the related kits, and the changes in the hepatic tissue reactive oxygen species (ROS) levels were detected by immunofluorescence (IF). The protein expression levels of cleaved caspase-3, GSDME-N, IL-1β, B-cell lymphoma-2 (Bcl-2), cytochrome C (Cyt-c), and acetaldehyde dehydrogenase 2 (ALDH2) were detected using western blotting. GSDME expression was detected by immunohistochemistry. ResultsCompared with the Sham group, CLP mice showed high sepsis scores and obvious liver damage. However, in the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups, the sepsis scores were reduced and liver injury was alleviated. Compared with the Sham group, the serum ALT and AST activities, MDA and ROS levels, and IL-1β and TNF-α concentrations were increased in the CLP group, as well as the protein expression of cleaved caspase-3, GSDME-N, IL-1β, Cyt-c, and GSDME positive cells (P < 0.05). However, the expression levels of Bcl-2 and ALDH2 protein were decreased (P < 0.05). Compared with the CLP group, the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups showed low sepsis scores, ALT and AST activities, MDA and ROS levels, decreased IL-1β and TNF-α concentrations, and decreased expression of cleaved caspase-3, GSDME-N, IL-1β protein expression, and GSDME positive cells (P < 0.05). The expression levels of Bcl-2 and ALDH2 protein were increased (P < 0.05). ConclusionApoptosis and GSDME-mediated pyroptosis are involved in the development of sepsis-induced hepatic injury. Inhibition of apoptosis and GSDME-mediated pyroptosis attenuates injury. ALDH2 plays a protective role by inhibiting apoptosis and pyroptosis.

Sodium acetate and sodium butyrate attenuate diarrhea in yak calves by regulating gut microbiota and metabolites

Diarrhea is a severe issue in calves that causes fertility problems and economic issues worldwide. Sodium acetate/sodium butyrate (SA/SB) alleviates diarrhea in mice; however, little information is available about the preventive effect of SA/SB on diarrheic yak calves living on the Tibet plateau. Yak calves (n = 19) of age ≥4 months and weight 37 ± 2 Kg were randomly divided into control (C, n = 10) and supplement groups (S, n = 9). Yaks belonging to the supplement group were given sodium butyrate (10 g/kg) and sodium acetate (5 g/kg) for 28 days, along with normal feed, seasonal grasses, pasture, and water. The blood and fecal samples from yak calves were collected for assessment of antioxidant capacity, inflammatory cytokines, microbiome, and short-chain fatty acids (SCFAs) concentration analysis. Results of this study revealed that a lower diarrhea rate, higher weight, and net weight gain were recorded in yaks belonging to group S supplemented with SA/SB. Similarly, increased antioxidant capacity with higher levels of T-AOC, SOD, and GSH-px and decreased inflammatory reactions by decreasing both TNF-α and IL-1β concentrations were recorded in yaks of group S. The concentration of SCFAs was significantly higher (p < 0.05) in yaks from group S than group C. Microbiome analysis revealed that 8 phyla and 54 genera were significantly different (p < 0.05) in both yak groups, with increased probiotics (Akkermansia, Oscillospira), SCFAs producing genera (Oscillospira, ASF356, Anaerosporobacter and Phascolarctobacterium), and decreased inflammatory related genus (Flavonifractor, Fournierella) and harmful bacteria (Oscillibacter, Achromobacter) in group S. In conclusion, the results demonstrated that SA and SB could decrease diarrhea rates in yak calves on the plateau via increasing antioxidant ability and SCFAs, while decreasing inflammatory responses in yaks by moderating gut microbiota. The current results provide new insights for the prevention and treatment of diarrhea in yaks.

Notoginsenoside R1 restrains the proliferation and migration of airway smooth muscle cells isolated from rats with chronic obstructive pulmonary disease

Objective Chronic obstructive pulmonary disease (COPD) is a common disorder that is characterized by systemic and lung inflammation. Notoginsenoside R1 (NGR1) displays anti-inflammatory properties in numerous diseases. We aimed to explore the function and mechanism of NGR1 in COPD. Materials and methods COPD rats were established through cigarette smoke exposure, lipopolysaccharide injection, and cold stimulation. Rat airway smooth muscle cells (ASMCs) were separated and identified. Then, ASMCs were treated with NGR1 (25 or 50 μM) and cigarette smoke extract (CSE). Thereafter, the vitality, proliferation, and migration of ASMCs were measured. Additionally, cell cycle, inflammation-related factors, α-SMA, and PI3K/AKT pathway-related marker expressions of the ASMCs were also detected. Molecular docking experiments were conducted to explore the interaction of NGR1 to PI3K, TGF-β, p65, and AKT. Moreover, 740 Y-P (a PI3K/Akt pathway agonist) were used to validate the mechanism of NGR1 on COPD. Results NGR1 inhibited the proliferation and migration, but caused cell cycle arrest for CSE-triggered ASMCs. Furthermore, NGR1 not only decreased IL-1β, IL-6, IL-8, and TNF-α contents, but also reduced α-SMA expression in CSE-stimulated ASMCs. Moreover, NGR1restrainedTGF-β1 expression, PI3K, p65, and AKT phosphorylation in CSE-stimulated ASMCs. Molecular docking experiments showed NGR1 exhibited a strong binding ability to PI3K, TGF-β1, p65, and AKT. Notably, the effects of NGR1 on the proliferation and migration of CSE-induced ASMCs were reversed by 740 Y-P. Conclusions NGR1 can restrain the proliferation and migration of CSE-induced ASMCs, indicating that NGR1 may be a therapeutic candidate for treating COPD.

The impact of age and sex on the inflammatory response during bone fracture healing.

Inflammation is thought to be dysregulated with age leading to impaired bone fracture healing. However, broad analyses of inflammatory processes during homeostatic bone aging and during repair are lacking. Here, we assessed changes in inflammatory cell and cytokine profiles in circulation and in bone tissue to identify age- and sex-dependent differences during homeostasis and repair. During homeostatic aging, male mice demonstrated accumulation of CD4+ helper T cells and CD8+ cytotoxic T cells within bone while both pro-inflammatory "M1" and anti-inflammatory "M2" macrophage numbers decreased. Female mice saw no age-associated changes in immune-cell population in homeostatic bone. Concentrations of IL-1β, IL-9, IFNγ, and CCL3/MIP-1α increased with age in both male and female mice, whereas concentrations of IL-2, TNFα, TNFR1, IL-4, and IL-10 increased only in female mice - thus we termed these "age-accumulated" cytokines. There were no notable changes in immune cell populations nor cytokines within circulation during aging. Sex-dependent analysis demonstrated slight changes in immune cell and cytokine levels within bone and circulation, which were lost upon fracture injury. Fracture in young male mice caused a sharp decrease in number of M1 macrophages; however, this was not seen in aged male mice nor in female mice of any age. Injury itself induced a decrease in the number of CD8+ T cells within the local tissue of aged male and of female mice but not of young mice. Cytokine analysis of fractured mice revealed that age-accumulated cytokines quickly dissipated after fracture injury, and did not re-accumulate in newly regenerated tissue. Conversely, CXCL1/KC-GRO, CXCL2/MIP-2, IL-6, and CCL2/MCP-1 acted as "fracture response" cytokines: increasing sharply after fracture, eventually returning to baseline. Collectively, we classify measured cytokines into three groups: (1) age-accumulated cytokines, (2) female-specific age-accumulated cytokines, and (3) fracture response cytokines. These inflammatory molecules represent potential points of intervention to improve fracture healing outcome.

Algorithm for predicting death in newborns with respiratory pathology and perinatal damage to the central nervous system on artificial ventilation

The objective was to predict the fatal outcome of the disease in newborns on artificial lung ventilation by means of an intelligent analysis of the immunological database.Materials and methods. The retrospective clinical study included 108 mature newborns. Upon admission to the intensive care unit, on the 3rdday and at the end of the disease, the plasma concentrations of IL-1β, IL-6, IL-8, TNF-α, G-CSF, s-Fas, FGF, NO were determined by ELISA; the relative content of CD3+CD19–, CD3–CD19+, CD3+CD4+, CD3+CD8+, CD69+, CD71+, CD95+, HLA-DR+, CD34+; CD14+, CD3–CD56+ by immunophenotyping; relative content of lymphocytes with expression of AnnexinV-FITC+PI–, AnnexinV-FITC+PI+. By the method of decision trees, the rule of predicting death was formulated.Results. The patient is predicted fatal outcome if, upon admission to intensive care, he has the relative content of lymphocytes with expression of AnnexinV-FITC+PI+ ≥ 0.95 % and plasma concentration of G-CSF ≤ 1.46 pg\ml or G-CSF ≥ 1.46 pg\ml and AnnexinV-FITC+PI+ ≥ 4.75 %(specificity 98.68 %; sensitivity 96.97 %; accuracy 98.68 %).Conclusion. In newborns with respiratory pathology and perinatal involvement of the central nervous system on artificial ventilation, death is determined by the high activity of T-lymphocyte apoptosis mediated by the low plasma concentration of granulocyte colony stimulating factor.

The dose-dependent neuroprotective effect of norepinephrine in improving memory retrieval in an experimental model of multiple sclerosis, experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is considered an immune-mediated inflammatory disorder that causes cognitive impairments by damaging the hippocampal tissue. Conversely, norepinephrine (NEP) has anti-inflammatory and re-myelinating properties, which improve cognitive impairments. The aim of this study was to assess the neuroprotective effects of NEP on learning and memory disorders in an experimental animal model of MS. Two guide cannulas were bilaterally implanted in the rat hippocampal CA1 regions. After recovery, the animals received 3 μl of 0.01% ethidium bromide (EtB) in each of both hippocampal regions. After three days, the rats were randomly divided into 6 groups (8 rats/group), including control, sham 1, sham 2, and three groups of NEP 0.25, 0.5, and 1 mg/kg by intrahippocampal injection. Behavioral tests (e.g. shuttle box test and open-field test) were then performed. Finally, ROS, MDA, GSH, TNF-α, IL-6, and IL-1β concentrations in the left CA1 area, as well as using western-blot analysis, p-p38, p-JNK, p-AKT, p-ERK1/2, p-NMDA, p-AMPA, p-CREB, and BDNF proteins in the right CA1 region evaluated. The EtB injection increased ROS, MDA, TNF-α, IL-6, and IL-1β levels, as well as p-JNK and p-P38, except all other proteins, while decreasing GSH content, as well as step-through latency and locomotor activity in sham groups compared to the control group. Conversely, NEP (0.5 and 1 mg/kg, particularly at the dose of 1 mg/kg) counterbalanced all the alterations mentioned above in comparison to the sham groups. The EtB induced learning and memory impairment; however, NEP dose-dependently restored these impairments to normal levels.

Expression of Inflammation Depending on the Stage of Cervical Cancer.

Background and Objectives: Cervical cancer (CC) remains a major public health problem, ranking as the fourth most common cause of cancer incidence and mortality in women globally. The development of CC is believed to be closely related to chronic inflammation. Thus, we aimed to evaluate the expression of systemic inflammation in patients with CC and to determine the threshold prognostic value of the systemic inflammation markers for CC and its advanced stage. Materials and Methods: 182 participants were recruited: 94 histology-proven patient with CC and 88 healthy women with NILM confirmed by liquid-based cytology test. The pre-treatment serum concentrations of cytokines, including IFN-β, IFN-γ, IL-1β, IL-2, IL-6, IL-10, IL-12p70, LCN2, TREM-1, and TNF-α, were determined for all study patients. Results: The odds ratio (OR) of having IL-6 concentration >17.4 pg/mL in the CC group compared to control patients was 11.4 (95% CI: 4.897-26.684); that of having TREM-1 concentration >355.6 pg/mL was 5.9 (95% CI: 2.257-15.767); and that of having LCN2 concentration >23,721.5 pg/mL was 3.4 (95% CI: 1.455-8.166). The odds ratio (OR) of having IL-6 concentration >28.7 pg/mL in advanced-stage CC (III-IV stage) compared to early-stage CC (I-II stage) was 2.921 (95% CI: 1.06-8.045), and that of having LCN2 concentration >25,640.0 pg/mL was 4.815 (95% CI: 1.78-13.026). Conclusions: The pre-treatment serum inflammation markers IL-6, TREM-1, and LCN2 at specified levels could be used as predictors of cervical cancer, and IL-6 and LCN2 as predictors of an increased chance of advanced-stage (III-IV stages) cervical cancer. Patients with cervical cancer had expressed systemic inflammation, and expression of inflammation elevated the chance of having CC and advanced-stage disease.

Linking Immunological Parameters and Recovery of Patient’s Motor and Cognitive Functions In The Acute Period of Ischemic Stroke

Objective. To evaluate the relationship between immunological parameters and functional outcome in patients with varying severity of ischemic stroke based on statistical methodology.Materials and methods. The prospective study included 78 patients diagnosed with ischemic stroke, who were distributed into two groups: group 1 — 38 mild stroke patients, NIHSS score &lt; 5, group 2 — 40 moderate stroke patients, NIHSS score 5–15. Signs of stroke severity, degree of disability, cognitive decline, and activities of daily living were chosen as criteria to estimate the functional outcome by calculating the difference between the NIHSS, mRS, MoCA, and BI scales at the time of admission and on Day 12 of hospital stay. Lab tests included assessment of plasma concentrations of CXC and CC subfamilies of cytokines, interleukins and TNF-a on Day 2 of hospital stay. Machine learning algorithms, the Python programming language, the Pandas and SciPy libraries, and discriminant analysis were used for statistical processing.Results. The following parameters were found as significant: concentrations of IL-1b and MPIF-1/CCL23 for — for group 1, and concentrations of IL-16, MPIF-1/CCL23, Eotaxin-2/CCL24, Gro-a/CXCL1 and IL-8/CXCL8 for group 2 patients. Positive correlation was established between NIHSS dynamics and concentrations of TNF-a (R=0.227, P=0.001), MPIF-1/CCL23 (R=0.380, P=0.00061) and Gro-a/CXCL1 (R=0.211, P=0.00001), and between changes in mRS and concentrations of MPIF-1/CCL23 (R=0.277, P=0.00006), Gro-a/CXCL1 (R=0.211, P=0.0075) and IL-16 (R=0, 211, P=0.00001). There was a significant negative correlation between cognitive dysfunction and concentrations of Eotaxin-2/CCL24 (R=–0.378, P=0.00075), Gro-a/CXCL1 (R=–0.313, P=0.0035), and IP-10/CXCL1 (R=–0.214, P=0.00023), and between limited activities of daily living (IB) and concentrations of MPIF-1/CCL23 (R=–0.345, P=0.0024) and Gro-a/CXCL1 (R=–0.210, P=0.00001).Conclusion. Chemokines form the CC family — MPIF-1/CCL23 and Eotaxin-2/CCL24, and the CXC-Gro-a/CXCL1 and IL-16 clusters are the principal cytokines associated with the dynamics of patient’s motor and cognitive functions recovery in the acute period of ischemic stroke. Although obtained results demonstrate negative effect of increased MPIF-1/CCL23, Gro-a/CXCL1, IL-16 and Eotaxin-2/CCL24 concentrations on the improvement of motor and cognitive impairments, further studies are needed to verify the CXC and CC subfamilies chemokines as prognostic markers of patient’s functional outcome in the acute period of ischemic stroke.

Trehalose promotes atherosclerosis regression in female mice.

Atherosclerosis is a chronic inflammatory disease caused by the deposition of lipids within the artery wall. During atherogenesis, efficient autophagy is needed to facilitate efferocytosis and cholesterol efflux, limit inflammation and lipid droplet buildup, and eliminate defective mitochondria and protein aggregates. Central to the regulation of autophagy is the transcription factor EB (TFEB), which coordinates the expression of lysosomal biogenesis and autophagy genes. In recent years, trehalose has been shown to promote TFEB activation and protect against atherogenesis. Here, we sought to investigate the role of autophagy activation during atherosclerosis regression. Atherosclerosis was established in C57BL/6N mice by injecting AAV-PCSK9 and 16 weeks of Western diet feeding, followed by switching to a chow diet to induce atherosclerosis regression. During the regression period, mice were either injected with trehalose concomitant with trehalose supplementation in their drinking water or injected with saline for 6 weeks. Female mice receiving trehalose had reduced atherosclerosis burden, as evidenced by reduced plaque lipid content, macrophage numbers and IL-1β content in parallel with increased plaque collagen deposition, which was not observed in their male counterparts. In addition, trehalose-treated female mice had lower levels of circulating leukocytes, including inflammatory monocytes and CD4+ T cells. Lastly, we found that autophagy flux in male mice was basally higher than in female mice during atherosclerosis progression. Our data demonstrate a sex-specific effect of trehalose in atherosclerosis regression, whereby trehalose reduced lipid content, inflammation, and increased collagen content in female mice but not in male mice. Furthermore, we discovered inherent differences in the autophagy flux capacities between the sexes: female mice exhibited lower plaque autophagy than males, which rendered the female mice more responsive to atherosclerosis regression. Our work highlights the importance of understanding sex differences in atherosclerosis to personalize the development of future therapies to treat cardiovascular diseases.

Pathophysiological profile of non-ventilated lung injury in healthy female pigs undergoing mechanical ventilation

BackgroundLung regions excluded from mechanical insufflation are traditionally assumed to be spared from ventilation-associated lung injury. However, preliminary data showed activation of potential mechanisms of injury within these non-ventilated regions (e.g., hypoperfusion, inflammation).MethodsIn the present study, we hypothesized that non-ventilated lung injury (NVLI) may develop within 24 h of unilateral mechanical ventilation in previously healthy pigs, and we performed extended pathophysiological measures to profile NVLI. We included two experimental groups undergoing exclusion of the left lung from the ventilation with two different tidal volumes (15 vs 7.5 ml/kg) and a control group on bilateral ventilation. Pathophysiological alteration including lung collapse, changes in lung perfusion, lung stress and inflammation were measured. Lung injury was quantified by histological score.ResultsHistological injury score of the non-ventilated lung is significantly higher than normally expanded lung from control animals. The histological score showed lower intermediate values (but still higher than controls) when the tidal volume distending the ventilated lung was reduced by 50%. Main pathophysiological alterations associated with NVLI were: extensive lung collapse; very low pulmonary perfusion; high inspiratory airways pressure; and higher concentrations of acute-phase inflammatory cytokines IL-6, IL-1β and TNF-α and of Angiopoietin-2 (a marker of endothelial activation) in the broncho-alveolar lavage. Only the last two alterations were mitigated by reducing tidal volume, potentially explaining partial protection.ConclusionsNon-ventilated lung injury develops within 24 h of controlled mechanical ventilation due to multiple pathophysiological alterations, which are only partially prevented by low tidal volume.

The Impact of Cytokines on Health-Related Quality of Life in Adolescents with Allergic Rhinitis.

Frequent episodes of nasal symptoms are the usual clinical manifestations (CM) of allergic rhinitis (AR) and have a significant negative impact on health-related quality of life (HRQoL) in adolescents. The purpose of this cross-sectional study was to test the hypothesis that cytokines in nasal mucus may be associated with HRQoL in adolescents with AR. European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L), "The Adolescent Rhinoconjunctivitis Quality of Life Questionnaire" (AdolRQLQ) and the Total 4 Symptom Score (T4SS) scoring system were administered to 113 adolescents with AR, nonallergic rhinitis (NAR) and to healthy control subjects. Nasal secretions were sampled and tested for 13 cytokines using a multiplex flow cytometric bead assay. The AR group had significantly lower EQ-5D-3L (0.661 ± 0.267 vs. 0.943 ± 0.088; p < 0.001) and higher AdolRQLQ total scores (2.76 ± 1.01 vs. 1.02 ± 0.10; p < 0.001) compared to the control group. The AR group had higher concentrations of IL-1β (p = 0.002), IL-6 (p = 0.031), IL-8 (p < 0.001), IL17-A (p = 0.013) and IL-18 (p = 0.014) compared to the control group, and IL-1β, IL-6, IL17-A and IL-18 were significantly (p < 0.050) increased with disease progression. Cytokines IL-1β, IL-6, as well as severe CM, were identified as significant predictors of lower HRQoL in adolescents with AR. This study identified IL-1β, IL-6, as well as severe CM, as predictors of lower HRQoL in adolescents with AR. However, these results should only serve as a starting point for additional confirmation research.

Matrine: A Promising Treatment for Ulcerative Colitis by Targeting the HMGB1/NLRP3/Caspase-1 Pathway.

Previous studies have found that matrine (MAT) effectively treated Ulcerative Colitis (UC). The purpose of this study is to explore its mechanism based on the HMGB1/NLRP3/Caspase-1 signaling pathway. MAT was administered intragastrically to DSS-induced UC mice for 14 days. The Disease Activity Index (DAI) and histological staining were measured to detect histopathological changes in colon. The levels of IL-1β, IL-6, and TNF-α in serum were measured by ELISA. The protein and mRNA expression of HMGB1/NLRP3/Caspase-1 in the colon were detected by immunohistochemistry, western Blotting or qRT-PCR. MAT improved the histological pathological changes of UC mice, as assessed by DAI, colonic length, and colonic mucosal injury. MAT also reduced colonic inflammatory damage by reducing the serum IL-1β, IL-6, and TNF-α content and decreasing the expression of HMGB1, NLRP3, Caspase-1, and IL-1β and proteins and mRNA in the colon. MAT could significantly alleviate DSS-induced UC symptoms by reducing the expressions of pro-inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, the mechanism of which is related to the inhibition of HMGB1/NLRP3/Caspase-1 signaling pathway.

Mussel oil is superior to fish oil in preventing atherosclerosis of ApoE-/- mice.

The present study aimed to explore the preventive effect of mussel oil (MO) on atherosclerosis and the potential mechanism in apolipoprotein E-null (ApoE-/-) mice. ApoE-/- mice were fed with a high-fat and high-cholesterol chow and given corn oil (CO), fish oil (FO), MO, or aspirin (ASP, dissolved in CO) by gavage for 12 weeks. The total n-3 polyunsaturated fatty acids (PUFAs) in MO (51.01%) and FO (46.82%) were comparable (mainly C22:6n-3 and C20:5n-3). Wild-type mice were fed with a normal chow and given equivalent CO as health control (CON). Compared with the CON group, obvious atherosclerotic plaque appeared at aorta and aortic sinus in the CO group. Compared with the CO group, MO but not FO had a significantly smaller atherosclerotic plaque area in the aorta. The aortic atherosclerotic plaque area was comparable in the MO, CON, and ASP groups. The MO group had a significantly smaller atherosclerotic plaque area, lower lipid deposition, lower contents of smooth muscle cell (SMC), and slightly lower contents of macrophage at the aortic sinus than the FO group. Serum concentrations of IL-1β, NF-κB, and VCAM-1 were comparable in the MO and FO groups and were significantly lower than the CO group. Compared with the CO group, the MO group but not FO group had significantly lower aortic protein levels of p65NF-κB, p38MAPK, and VCAM-1. The aortic protein levels of p-p65NF-κB and p-p38MAPK were significantly lower in the MO group than the FO group. In conclusion, MO is more potent than FO in preventing atherosclerosis, and the possible mechanism may be by downregulating p38MAPK/NF-κB signaling pathway, decreasing VCAM-1 and macrophage, and inhibiting proliferation and migration of SMC.

Evaluation of the Association between Genetic Polymorphism of Interleukin-1 Beta (–511C/T and +3953C/T) and Cervical Cancer Susceptibility

Cervical cancer (CC) is the leading cause of cancer-related mortality among women, primarily caused by persistent human papillomavirus (HPV) infection, especially in developing countries. A proinflammatory cytokine, emerging as a major facilitator of carcinogenesis, is termed interleukin-1 beta (IL-1β), which characterizes host-environment interactions. Numerous epidemiological studies have revealed that IL-1β gene polymorphisms have been associated with numerous malignancies, but in the context of CC, results of these studies were inconclusive. Thus, our study aimed to explore the relationship between IL-1β polymorphisms (-511C/T and +3953C/T) and CC susceptibility. Genotyping was conducted on 192 CC patients and 200 healthy controls through polymerase chain reaction-restricted fragment length polymorphism. HPV analysis was done through real-time polymerase chain reaction, and the serum concentration of IL-1β was measured by enzyme-linked immunosorbent assay. Women with CT and TT genotypes of IL-1β -511C/T had a threefold increased risk of CC (odds ratio [OR], 3.60; 95% confidence interval [CI], 2.132-6.063; p &lt; 0.001 vs. OR, 3.34; 95% CI, 1.952-5.713; p &lt; 0.001) compared to controls. Women with the T allele of IL-1β -511C/T polymorphism were associated with increased CC susceptibility (OR, 2.00; 95% CI, 1.51-2.66; p = 0.0001) compared to controls. No significant difference was found between patients and controls in the genotype or allele frequencies of IL-1β +3953C/T polymorphism (OR, 0.93; 95% CI, 0.56-1.55; p = 0.86 vs. OR, 0.95; 95% CI, 0.72-1.26; p = 0.74). There was no significant association found between IL-1β -511C/T promoter (OR, 2.41; 95% CI, 0.46-12.76; p = 0.28 vs. OR, 1.64; 95% CI, 0.13-21.10; p = 0.7) and +3953C/T (OR, 3.76; 95% CI, 0.44-31.82; p = 0.19 vs. OR, 0.21; 95% CI, 0.01-3.92; p = 0.25) polymorphisms in tobacco chewers and smokers compared to controls. The level of serum concentration of IL-1β was significantly higher in cases compared to controls. Our results conclude that IL-1β -511C/T polymorphism is associated with CC susceptibility.

The effect of human PBMCs immobilization on their Аβ42 aggregates-dependent proinflammatory state on a cellular model of Alzheimer's disease.

The leading pathological mechanisms of Alzheimer's disease are amyloidosis and inflammation. The presented work was aimed to study the effect of human peripheral blood mononuclear cells (hPBMcs) cells-matrix adhesion on their pro-inflammatory state in vitro. Although direct interaction of Аβ42 to PBMC is not a cellular model of Alzheimer's disease, PBMCs may serve as test cells to detect Аβ42-dependent molecular effects in monitoring disease progression. Peripheral blood mononuclear cells (PBMCs) are used to assess changes in cytokines released in response to diseases or Alzheimer's disease-specific cytotoxic molecules such as Aβ42. The effect of recombinant amyloid β-peptide rАβ42 on the concentration of endogenous amyloid β-peptide Aβ40 and pro-inflammatory cytokines TNFα and IL-1β in human peripheral blood mononuclear cells that were cultured in suspension and immobilized in alginate microcarriers for 24 h were investigated. The localization and accumulation of Aβ40 and rAβ42 peptides in cells, as well as quantitative determination of the concentration of Aβ40 peptide, TNFα and IL-1β cytokines, was performed by intravital fluorescence imaging. The results were qualitatively similar for both cell models. It was determined that the content of TNFα and Aβ40 in the absence of rAβ42 in the incubation medium did not change for 24 h after incubation, and the content of IL-1β was lower compared to the cells that were not incubated. Incubation of cells in vitro with exogenous rAβ42 led to an increase in the intracellular content of TNFα and Aβ40, and no accumulation of IL-1β in cells was observed. The accumulation of Aβ40 in the cytoplasm was accompanied by the aggregation of rAβ42 on the outer surface of the cell plasma membrane. It was shown that the basic levels of indicators and the intensity of the response of immobilized cells to an exogenous stimulus were significantly greater than those of cells in suspension. To explore whether non-neuronal cells effects in alginate microcarriers were cell-matrix adhesion mediated, we tested the effect of blocking β1 integrins on proamyloidogenic and proinflammation cellular state. Immobilization within alginate hydrogels after incubation with the β1 integrins blocking antibodies showed a remarkable inhibition of TNFα and Aβ40 accumulation in rAβ42-treated cells. It can be concluded that activation of signal transduction and synthesizing activity of a portion of mononuclear cells of human peripheral blood is possible (can significantly increase) in the presence of cell-matrix adhesion.