Abnormal Inflammatory Reaction Research Articles

Effects of aquatic Ca2+ and Mg2+ on the antioxidant, immune, osmotic regulation, molting, and metabolic abilities of Scylla paramamosain

Current saline-alkali aquaculture of the saline alkali-tolerant mud crab Scylla paramamosain fails to meet market demand. Given that Ca2+ and Mg2+ are closely related to growth in crustaceans, physiological responses of mud crab to different levels of these ions at varying salinity levels were explored. Long-term aquaculture experiments were conducted by adding CaCl2, MgCl2, and NaCl to the water to control Ca2+, Mg2+ and salinity levels. Three different ratios and concentrations of Ca2+ and Mg2+ were established (Sanmen area, SM group; Cangnan area, CN group; Rui'an area, RA group); in addition, four different salinity groups (3, 8, 10, and 12 ‰) were established under each of the Ca2+–Mg2+ treatment groups At Ca2+:Mg2+ ratios of 300:900 (SM) and 400:1200 mg (CN), S. paramamosain showed stronger osmotic regulation and higher Na+/K+-ATPase and Ca2+/Mg2+-ATPase activity compared with those reared at a Ca2+: Mg2+ ratio of 300:300 (RA). Indicators of hepatopancreas injury also increased in the RA group with time, indicating lipid metabolism disorders and abnormal inflammatory reactions. Immune and antioxidant enzyme activity increased with time in the SM and CN groups, but decreased in the RA group. In addition, malondialdehyde increased with time in the RA group, but remained constant in the SM and CN groups under normal salinity and decreased under low salinity. Thus, cultivation under 300: 900 or 400: 1200 Ca2+: Mg2+ ratios enhanced the immune and antioxidant abilities of mud crab, as well as its ability to alleviate damage caused by low-salt stress. Upregulation of various energy substrates in the CN group under low-salt stress indicated the mobilization of energy reserves to support osmotic regulation. At a salinity of 3 ‰, the CN group also had more pathways upregulated related to energy metabolism, ion transport, and antioxidation, whereas, at 12 ‰, more antioxidant pathways were upregulated. A 120-day aquacultural experiment confirmed that the SM and CN groups showed better growth performance compared with the RA group. Overall, these results confirm that conditions in the SM and CN groups were more suitable for the aquaculture of mud crab, providing a theoretical guidance for increasing mud crab production in saline-alkali fishery.

(-)-Epicatechin gallate prevented atherosclerosis by reducing abnormal proliferation of VSMCs and oxidative stress of AML 12 cells

(−)-Epicatechin gallate (ECG) is beneficial to the treatment of cardiovascular diseases (CVDs), especially atherosclerosis (AS) through antioxidant stress, but there is a lack of detailed mechanism research. In this study, the therapeutic target of ECG was determined by crossing the drug target and disease target of CVDs and AS. The combination ability of ECG with important targets was verified by Discovery Studio software. The abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by Ang-II and the oxidative damage of AML 12 induced by H2O2 were established to verify the reliability of ECG intervention on the target protein. A total of 120 ECG targets for the treatment of CVDs-AS were predicted by network pharmacology. The results of molecular docking showed that ECG has strong binding force with VEGFA, MMP-9, CASP3 and MMP-2 domains. In vitro experiments confirmed that ECG significantly reduced the expression of VEGFA, MMP-9, CASP3 and MMP-2 in Ang-II-induced VSMCs, and also blocked the abnormal proliferation, oxidative stress and inflammatory reaction of VSMCs by inhibiting the phosphorylation of PI3K signaling pathway. At the same time, ECG also interfered with H2O2-induced oxidative damage of AML 12 cells, decreased the expression of ROS and MDA and cell foaming, and increased the activities of antioxidant enzymes such as SOD, thus playing a protective role.

Plant-derived exosome-like nanoparticles for microRNA delivery in cancer treatment.

Plant-derived exosome-like nanoparticles (PELNs) are natural nanocarriers and effective delivery systems for plant microRNAs (miRNAs). These PELN-carrying plant miRNAs can regulate mammalian genes across species, thereby increasing the diversity of miRNAs in mammals and exerting multi-target effects that play a crucial role in diseases, particularly cancer. PELNs demonstrate exceptional stability, biocompatibility, and targeting capabilities that protect and facilitate the up-take and cross-kingdom communication of plant miRNAs in mammals. Primarily ingested and absorbed within the gastrointestinal tract of mammals, PELNs preferentially act on the intestine to regulate intestinal homeostasis through functional miRNA activity. The oncogenesis and progression of cancer are closely associated with disruptions in intestinal barriers, ecological imbalances, as well as secondary changes, such as abnormal inflammatory reactions caused by them. Therefore, it is imperative to investigate whether PELNs exert their anticancer effects by regulating mammalian intestinal homeostasis and inflammation. This review aims to elucidate the intrinsic crosstalk relationships and mechanisms of PELNs-mediated miRNAs in maintaining intestinal homeostasis, regulating inflammation and cancer treatment. Furthermore, serving as exceptional drug delivery systems for miRNAs molecules, PELNs offer broad prospects for future applications, including new drug research and development along with drug carrier selection within targeted drug delivery approaches for cancer therapy.

IGF2BP2 regulates the inflammation of fibroblast-like synoviocytes via GSTM5 in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease with an unknown etiology. RA cannot be fully cured and requires lengthy treatment, imposing a significant burden on both individuals and society. Due to the lack of specific drugs available for treating RA, exploring a key new therapeutic target for RA is currently an important task. Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the progression of RA, which release interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α resulting in abnormal inflammatory reaction in the synovium. A previous study has highlighted the correlation of m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) with inflammation-related diseases in human. However, the role of IGF2BP2 in the inflammatory reaction of FLSs during RA progression has not been assessed. In this study, IGF2BP2 expression was decreased in the synovial tissues of RA patients and collagen-induced arthritis (CIA) rats. Intra-articular injection of an adeno-associated virus (AAV) vector overexpressing IGF2BP2 relieved paw swelling, synovial hyperplasia and cartilage destruction in CIA rats. IGF2BP2 overexpression also inhibited lipopolysaccharide (LPS)-mediated RA fibroblast-like synoviocytes (RA-FLSs) migration and invasion accompanied by a decreased level of inflammatory factors in vitro. Conversely, IGF2BP2 suppression promoted RA-FLSs migration and invasion with an elevated level of inflammatory factors in vitro. The sequencing result showed that glutathione S-transferase Mu 5 (GSTM5), a key antioxidant gene, was the target mRNA of IGF2BP2. Further experiments demonstrated that IGF2BP2 strengthened the stability of GSTM5 mRNA, leading to weakened inflammatory reaction and reduced expression of matrix metalloproteinase 9 and 13 (MMP9, MMP13). Therefore, IGF2BP2-GSTM5 axis may represent a potential therapeutic target for RA treatment.

Gut microbiota-derived 5-hydroxyindoleacetic acid from pumpkin polysaccharides supplementation alleviates colitis via MAPKs-PPARγ/NF-κB inhibition

Polysaccharides from Pumpkin (Cucurbita moschata Duchesne) (PPs) have many pharmacological activities, including anti-oxidant, immune, and intestinal microbiota regulation. These activities have provided some reminders of its potential therapeutic effect on ulcerative colitis (UC), but this has not yet been confirmed. This study preliminarily confirmed its significant anti-UC activity superior to Salicylazosulfapyridine. The average molecular weight of PPs was 3.10 × 105 Da, and PPs mainly comprised Mannose, Rhamnose, Galacturonic acid, Galactosamine, Glucose, and Xylose with molar ratios of 1.58:3.51:34.54:1.00:3.25:3.02. PPs (50, 100 mg/kg) could significantly resist dextran sodium sulfate induced UC on C57BL/6 mice by improving gut microbiota dysbiosis, such as the changes of relative abundance of Bacteroides, Culturomica, Mucispirillum, Escherichia-Shigella, Alistipes and Helicobacter. PPs also reverse the abnormal inflammatory reaction, including abnormal level changes of TNF-α, IFN-γ, IL-1β, IL-4, IL-6, IL-10, and IL-18. Metabolomic profiling showed that PPs supplementation resulted in the participation of PPAR and MAPK pathways, as well as the increase of 5-hydroxyindole acetic acid (5-HIAA) level. 5-HIAA also exhibited individual and synergistic anti-UC activities in vivo. Furthermore, combination of PPs and 5-HIAA could also elevate the levels of PPARγ in nuclear and inhibit MAPK/NF-ĸB pathway in the colon. This study revealed that PPs and endogenous metabolite 5-HIAA might be developed to treat UC.

Modified blade: an interventional option in rigid bronchoscopy for non-resectable benign tracheal stenosis

IntroductionBenign tracheobronchial stenosis is a abnormal tracheal lumen narrowing that may incur progressive dyspnea and life-threatening hypoxemia. There is no consensus on which patients should be treated with endoscopic or surgical method. This study investigates the outcomes of bronchoscopic dilatation in the treatment of benign tracheal stenosis using a device equipped with a blade to cut the stenotic lesions with dense fibrosis.Materials and methodsThe procedure was carried out in an operating room under general anesthesia. All patients were intubated with a Rigid Bronchoscope (RB) placed just above the stenosis. Through Rigid Bronchoscopy combined modalities were used as needed: radial incisions of the mucosal stenosis with blade at the levels of 4, 8 and 12 o’clock, with back and forth movements, then the stenotic area was dilated more easily with a rigid bronchoscope. Dilatation was performed by passing the RB of increasing diameter through stenotic areas and then Balloon dilatation of increasing diameter. There were no complications during the procedure.ResultWe conducted an observational, retrospective, single-centre study in the Thoracic Surgery Unit of the University of ‘Luigi Vanvitelli’ of Naples from November 2011 to September 2021. We included all consecutive patients with benign tracheal stenosis inoperable. During the study period, 113 patients were referred to our department with benign tracheal stenosis inoperable. 61 patients were treated with the blade. During the follow-up, a recurrence of the stenosis was observed in 8 patients in the first month and in 4 patients in the third month. Instead in the patients treated with the use of laser (52 patients), during the follow-up a recurrence was observed in 16 patients in the first month and in 6 patients in the third month; no patient relapsed after 6 months and after 1 year. Long term successful bronchoscopic management with blade was attained by 99% in simple and 93% in mixed stenosis and in complex type stenosis.ConclusionOur study underlines the importance of the use of the blade in bronchoscopic treatment as a valid conservative approach in the management of patients with inoperable benign tracheal stenosis as an alternative to the use of the laser, reducing the abnormal inflammatory reaction in order to limit recurrences.

The associations between dietary fibers intake and systemic immune and inflammatory biomarkers, a multi-cycle study of NHANES 2015-2020.

In recent years, there has been considerable growth in abnormal inflammatory reactions and immune system dysfunction, which are implicated in chronic inflammatory illnesses and a variety of other conditions. Dietary fibers have emerged as potential regulators of the human immune and inflammatory response. Therefore, this study aims to investigate the associations between dietary fibers intake and systemic immune and inflammatory biomarkers. This cross-sectional study used data from the National Health and Nutrition Examination Survey (2015-2020). Dietary fibers intake was defined as the mean of two 24-h dietary recall interviews. The systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), red blood cell distribution width-to-albumin ratio (RA), ferritin, high-sensitivity C-reactive protein (hs-CRP), and white blood cell (WBC) count were measured to evaluate systemic immune and inflammatory states of the body. The statistical software packages R and EmpowerStats were used to examine the associations between dietary fibers intake and systemic immune and inflammatory biomarkers. Overall, 14,392 participants were included in this study. After adjusting for age, gender, race, family monthly poverty level index, alcohol consumption, smoking status, vigorous recreational activity, body mass index, hyperlipidemia, hypertension, diabetes, and dietary inflammatory index, dietary fibers intake was inversely associated with SII (β = -2.19885, 95% CI: -3.21476 to -1.18294, p = 0.000248), SIRI (β = -0.00642, 95% CI: -0.01021 to -0.00263, p = 0.001738), NLR (β = -0.00803, 95% CI: -0.01179 to -0.00427, p = 0.000284), RA (β = -0.00266, 95% CI: -0.00401 to -0.00131, p = 0.000644), ferritin (β = -0.73086, 95% CI: -1.31385 to -0.14787, p = 0.020716), hs-CRP (β = -0.04629, 95% CI: -0.0743 to -0.01829, p = 0.002119), WBC (β = -0.01624, 95% CI: -0.02685 to -0.00563, p = 0.004066), neutrophils (β = -0.01346, 95% CI: -0.01929 to -0.00764, p = 0.000064). An inverse association between dietary fibers and PLR was observed in the middle (β = -3.11979, 95% CI: -5.74119 to -0.4984, p = 0.028014) and the highest tertile (β = -4.48801, 95% CI: -7.92369 to -1.05234, p = 0.016881) and the trend test (βtrend = -2.2626, 95% CI: -3.9648 to -0.5604, Ptrend = 0.0150). The observed associations between dietary fibers intake and SII, SIRI, NLR, RA, ferritin, hs-CRP, WBC, and neutrophils remained robust and consistent in the sensitivity analysis. No significant interaction by race was found. Dietary fibers intake is associated with the improvement of the parameters of the immune response and inflammatory biomarkers, supporting recommendations to increase dietary fibers intake for enhanced immune health.

Current views on pathogenesis of rosacea

Rosacea is a chronic inflammatory disease that usually affects the central part of the face. The primary symptoms include facial flushing, persistent erythema, telangiectasia, inflammatory pustules and papules. Based on groups of these symptoms, four basic rosacea subtypes have been defined: erythematotelangiectatic, papulopustular, ocular, phymatous; and one variant, granulomatous rosacea. Although the pathophysiology of this disorder is not fully known, many components such as immune and neurovascular dysregulation, oxidative stress, genetic background, gut microbiome, skin microbiome as well as external aspects are thought to play a role. In this article, we present the main factors that are speculated to be involved in the pathogenesis of rosacea. Methods and materials: We reviewed the literature available on PubMed and Google Scholar using the words "rosacea”, „rosacea pathogenesis”, „demodex”, „reactive oxygen species”, „rosacea microbiome”. Summary Rosacea is a chronic dermatosis whose etiology, despite many studies, is not fully understood. Currently, an abnormal inflammatory reaction caused by excessive stimulation of TLR-2 receptors is suspected as the main factor in the pathomechanism of the disease. Vascular disorders, transmission disorders, genetic factors, skin and intestinal dysbiosis also participate in the pathogenesis of rosacea. It is assumed that exogenous factors such as diet and exposure to UV radiation also play a role in the development of the disease.

Bionic artificial penile Tunica albuginea

Bionic artificial penile Tunica albuginea

1,25(OH)2D3 alleviates LPS-induced preeclampsia-like rats impairment in the protective effect by TLR4/NF-kB pathway

IntroductionAccumulating epidemiological studies support that Vitamin D deficiency is associated with the pathogenesis of preeclampsia. However, it is unknown whether vitamin D can be used as a treatment for preeclampsia. This study aimed to explore whether vitamin D supplementation could improve the rat model of preeclampsia. MethodsLPS was used to establish a rat model of preeclampsia. Inflammatory cytokines were examined by QRT-PCR and ELISA assays, and the concentration of sfit-1 and NO was assessed by ELISA. Analyzing the pathological features of the placenta with hematoxylin-eosin. The spatial learning and memory abilities of offspring were evaluated by the Morris water maze. Immune histology and western blot were performed to evaluate the expression levels of inflammatory pathway-associated Factor and vascular endothelium-associated Factor in the placenta. ResultsVitamin D treatment reduced the blood pressure and urine protein of PE model rats, alleviated pathological damage to the placenta and pregnancy outcomes, and protected PE offspring from impaired memory and learning abilities. Moreover, TLR4 signaling pathway in the placenta was inhibited. Furthermore, vitamin D supplementation increased the expression of endothelial growth factor and vascular relaxing factor, and there was no significant difference compared with the control group. DiscussionWe generated the result that Vitamin D supplementation significantly improved the phenotype of preeclampsia and adverse pregnancy outcome caused by an abnormal inflammatory reaction and endothelial dysfunction in the placenta, and improved the learning and cognitive ability of offspring.

Patients with ankylosing spondylitis have high risk of irritable bowel syndrome: a long-term nationwide population-based cohort study

ABSTRACT Objective Ankylosing spondylitis (AS) is a chronic inflammatory disease, might carry a high risk of irritable bowel syndrome (IBS) due to abnormal gut microbiota or inflammatory reaction. Methods We conducted a 14-year retrospective cohort study based on Taiwan’s National Health Insurance Research Database (NHIRD). A total of 4007 patients with newly diagnosed AS (outpatient visits≧3 times, or hospitalization≧1 time) and 988,084 non-AS comparisons were enrolled during 2000–2012. To ensure baseline comparability, the propensity score was matched by age, gender, comorbidities, and other possible confounders. The outcome was the incidence of IBS, followed up to the end of 2013. Cox proportional hazard model calculated adjusted hazard ratio (aHR) and the cumulative incidence of both groups was analyzed by the Kaplan-Meier method. Result After propensity score matching, baseline demographic characteristics were comparable between AS patients and the comparison group. The crude HR for IBS in the AS group was significantly higher 2.41 (95%C.I. = 1.84–3.16) than comparison group. After adjusting for possible confounders, adjusted HR was 2.50 (95%C.I. = 1.91–3.29). The cumulative incidence of IBS in AS was significantly higher than non-AS comparisons during the 14-year follow-up (P < 0.001). Conclusion This nationwide population-based cohort study showed that patients with AS have higher risks of IBS than those of the non-AS comparison group.

The Immunogenetics of Photodermatoses.

Photodermatosis is an abnormal skin inflammatory reaction to light. The major classifications of photodermatoses are idiopathic photodermatoses, photodermatoses due to exogenous or endogenous agents, photo-exacerbated dermatoses, and photosensitive genodermatoses. In this chapter, we focus on idiopathic photodermatoses and drug-related photodermatoses and emphasize on the epidemiology and immunogenetic backgrounds. Idiopathic photodermatoses, a spectrum of diseases with abnormal responses to ultraviolet radiation (UVR), include polymorphous light eruption, actinic prurigo, hydroa vacciniforme, chronic actinic dermatitis, and solar urticaria. Young people are more susceptible to most idiopathic photodermatoses except for chronic actinic dermatitis. Interestingly, idiopathic photodermatoses exhibit different characteristics between Caucasians and Asians. For example, the average age of Asian actinic prurigo patients is older than that of Caucasians in which genetic backgrounds or Fitzpatrick skin type might play a role. Drug-induced photodermatoses can be classified into phototoxic and photoallergic drug reactions. Certain drug-induced photodermatoses may mimic other dermatoses. For instance, drug-induced lupus erythematosus (LE) should be considered if an old man is diagnosed with LE but had a poor response to standard treatments.

Non-invasive ventilation in acute exacerbation of COPD with mild to moderate type 2 respiratory failure

Chronic obstructive pulmonary disease is a syndrome of progressive airflow limitation caused by abnormal inflammatory reaction of airway and lung parenchyma. Risk factor for development of COPD is a complex interaction of genetic factors and many environmental exposures, with the cigarette smoking being the most common etiological agent.It is a prospective observational comparative study conducted among patient with mild to moderate type 2 respiratory failure, secondary to acute exacerbation of Chronic Obstructive Pulmonary Disease admitted in chest ward department of Respiratory medicine, Late Shri Lakhi Ram Agrawal Memorial Medical College, Raigarh, Chhattisgarh, India for a period of one year from April 2020- April 2021.A total 60 patients were studied. Out of which, 30 patients in study group for whom non-invasive ventilation support along with conventional treatment was given and remaining 30 patients in comparison group, same treatment was given without non-invasive ventilation support. Both groups had similar demographic, clinical, biochemical profile at the time of admission. Distribution of comorbidities, smoking history were similar as shown below in tables. After application of Non-invasive ventilation along with conventional treatment in study group, the result showed that mean hours of NIV use in study group was 27 hours and mean hours of Oxygen use in comparison group was 98 hours.Use of non-invasive ventilation in acute exacerbation of COPD, with mild to moderate type 2 respiratory failure, reduced tachypnoea, tachycardia, after 4 hours. There were improvement in oxygen saturation after 4 hours, improvement in PH also occurred after 4 hours by 0.04. Non-invasive ventilation gives rest to fatigued inspiratory muscle so work of breathing is reduced. It also restores functional and biochemical changes associated with fatigued muscle so all complication were reduced with use of non- invasive ventilation.

Osteogenesis and angiogenesis of a bulk metallic glass for biomedical implants

Implantation is an essential issue in orthopedic surgery. Bulk metallic glasses (BMGs), as a kind of novel materials, attract lots of attentions in biological field owing to their comprehensive excellent properties. Here, we show that a Zr61Ti2Cu25Al12 (at. %) BMG (Zr-based BMG) displays the best cytocompatibility, pronounced positive effects on cellular migration, and tube formation from in-vitro tests as compared to those of commercial-pure titanium and poly-ether-ether-ketone. The in-vivo micro-CT and histological evaluation demonstrate the Zr-based BMG can significantly promote a bone formation. Immunofluorescence tests and digital reconstructed radiographs manifest a stimulated effect on early blood vessel formation from the Zr-based BMG. Accordingly, the intimate connection and coupling effect between angiogenesis and osteogenesis must be effective during bone regeneration after implanting Zr-based BMG. Dynamic gait analysis in rats after implanting Zr-based BMG demonstrates a tendency to decrease the pain level during recovery, simultaneously, without abnormal ionic accumulation and inflammatory reactions. Considering suitable mechanical properties, we provide a realistic candidate of the Zr61Ti2Cu25Al12 BMG for biomedical applications.

Systemic and organ-specific immune-related manifestations of COVID-19.

Immune-related manifestations are increasingly recognized conditions in patients with COVID-19, with around 3,000 cases reported worldwide comprising more than 70 different systemic and organ-specific disorders. Although the inflammation caused by SARS-CoV-2 infection is predominantly centred on the respiratory system, some patients can develop an abnormal inflammatory reaction involving extrapulmonary tissues. The signs and symptoms associated with this excessive immune response are very diverse and can resemble some autoimmune or inflammatory diseases, with the clinical phenotype that is seemingly influenced by epidemiological factors such as age, sex or ethnicity. The severity of the manifestations is also very varied, ranging from benign and self-limiting features to life-threatening systemic syndromes. Little is known about the pathogenesis of these manifestations, and some tend to emerge within the first 2 weeks of SARS-CoV-2 infection, whereas others tend to appear in a late post-infectious stage or even in asymptomatic patients. As the body of evidence comprises predominantly case series and uncontrolled studies, diagnostic and therapeutic decision-making is unsurprisingly often based on the scarcely reported experience and expert opinion. Additional studies are required to learn about the mechanisms involved in the development of these manifestations and apply that knowledge to achieve early diagnosis and the most suitable therapy.

Circadian rhythm disorder: a potential inducer of vascular calcification?

Over the past decades, circadian rhythm has drawn a great attention in cardiovascular diseases. The expressions of rhythm genes fluctuate in accordance with the diurnal changes of vascular physiology, which highlights the pivotal effect of vascular clock. Recent researches show that the circadian clock can directly regulate the synthetic and secretory function of endothelial cells and phenotypic switch of vascular smooth muscle cells to adjust vascular relaxation and contraction. Importantly, dysfunction of vascular cells is involved in vascular calcification. Secretion of osteogenic cytokines and calcified vesicles in the vessel, osteogenic phenotype switch of vascular smooth muscle cells are all implicated in the calcification process. Moreover, circadian rhythm disorder can lead to abnormal hormone secretion, oxidative stress, inflammatory reaction, and autophagy, all of which should not be ignored in vascular calcification. Vascular senescence is another pathogenetic mechanism in vascular calcification. Accelerated vascular senescence may act as an important intermediate factor to promote vascular calcification in circadian rhythm disorders. In this review, we elaborate the potential effect of circadian rhythm disorder in vascular calcification and try to provide a new direction in the prevention of vascular calcification.

Protective Effect of Pravastatin on Myocardial Ischemia Reperfusion Injury by Regulation of the miR-93/Nrf2/ARE Signal Pathway.

PurposeThis research intended to study the mechanism of pravastatin in myocardial ischemia reperfusion (I/R) injury.Patients and MethodsAltogether 70 male rats were selected and grouped into Sham operation group (Sham group), ischemia reperfusion group (I/R group), pravastatin pretreatment group (I/R+P group), I/R+miR-93-mimics, I/R+P+miR-93-mimics, I/R+Nrf2 siRNA, and I/R+P+Nrf2 siRNA group. The myocardial function of each group was detected.ResultsMyocardial I/R injury could lead to abnormal myocardial enzyme activity, inflammatory reaction and oxidative stress. However, pravastatin could significantly inhibit the activity of myocardial enzymes, alleviate inflammatory reaction and inhibit oxidative stress reaction, thus playing a protective role. Furthermore, cell experiments showed that pravastatin can alleviate the injury of H9C2 myocardial cells caused by I/R, inhibit the apoptosis of myocardial cells, and lead to a significant reduction in pro-apoptotic genes Bax, caspase-3 and caspase-9 transcription levels, an obvious increase in anti-apoptotic gene Bcl-2, and an increase in cell activity. After I/R induced injury, miR-93 level was significantly up-regulated and Nrf2 level was down-regulated. Over-expression of miR-93 or inhibition of Nrf2 expression would lead to further aggravation of I/R myocardial injury, increase the apoptosis rate of cells and decrease the activity of myocardial cells. Pravastatin administration could inhibit miR-93, activate and promote Nrf2 in myocardial tissue, and promote protein expression of downstream regulatory genes HO-1 and NQO1. In the I/R model, pravastatin was given. Over-expression of miR-93 or silencing Nrf2 could reverse the therapeutic effect of pravastatin on I/R.ConclusionPravastatin acts as a protector on myocardial ischemia reperfusion injury by regulating miR-93/Nrf2/ARE signaling pathway.

Vascular Endothelial Glycocalyx as a Mechanism of Vascular Endothelial Dysfunction and Atherosclerosis

Atherosclerosis occurs as a result of organized processes that include vascular endothelial dysfunction, lipid accumulation, abnormal inflammatory reaction, excessive reactive oxygen species production, and vascular cell proliferation and migration. In patients with atherosclerosis, vascular endothelial dysfunction is commonly observed with the damage of vascular endothelial glycocalyx, which is an extracellular matrix bound to and encapsulating the endothelial cells that line the blood vessel wall. Unhealthy lifestyle choices such as smoking and physical inactivity also induce glycocalyx degradation. Additionally, vascular endothelial glycocalyx can be damaged by various pathological conditions including dehydration, acute infectious disease, trauma, sepsis, acute respiratory distress syndrome, Kawasaki disease, preeclampsia, gestational diabetes mellitus, hypertension, diabetes mellitus, chronic kidney disease, atherosclerosis, stroke, dementia, microvascular angina, acute coronary syndrome, and heart failure. Vascular endothelial glycocalyx has been shown to be important as a physical cytoprotective barrier for vascular endothelial cells and as a regulatory mechanism for intracellular cell signaling. Therefore, vascular endothelial glycocalyx has immense potential in the exploration of novel strategies for the evaluation of beneficial conditions of healthy vasculature.

Intranasal Administration of Mesenchymal Stem Cells Ameliorates the Abnormal Dopamine Transmission System and Inflammatory Reaction in the R6/2 Mouse Model of Huntington Disease.

Intrastriatal administration of mesenchymal stem cells (MSCs) has shown beneficial effects in rodent models of Huntington disease (HD). However, the invasive nature of surgical procedure and its potential to trigger the host immune response may limit its clinical use. Hence, we sought to evaluate the non-invasive intranasal administration (INA) of MSC delivery as an effective alternative route in HD. GFP-expressing MSCs derived from bone marrow were intranasally administered to 4-week-old R6/2 HD transgenic mice. MSCs were detected in the olfactory bulb, midbrain and striatum five days post-delivery. Compared to phosphate-buffered saline (PBS)-treated littermates, MSC-treated R6/2 mice showed an increased survival rate and attenuated circadian activity disruption assessed by locomotor activity. MSCs increased the protein expression of DARPP-32 and tyrosine hydroxylase (TH) and downregulated gene expression of inflammatory modulators in the brain 7.5 weeks after INA. While vehicle treated R6/2 mice displayed decreased Iba1 expression and altered microglial morphology in comparison to the wild type littermates, MSCs restored both, Iba1 level and the thickness of microglial processes in the striatum of R6/2 mice. Our results demonstrate significantly ameliorated phenotypes of R6/2 mice after MSCs administration via INA, suggesting this method as an effective delivering route of cells to the brain for HD therapy.

Expression and significance of miR-126 and VEGF in proliferative diabetic retinopathy

Objective To investigate the expression and clinical significance of miR-126 and vascular endothelial growth factor (VEGF) in proliferative diabetic retinopathy (PDR). Methods 226 cases of diabetic retinopathy (DR) patients admitted in our hospital were studied, including 110 cases of PDR (group PDR), 116 non proliferative diabetic retinopathy (NPDR) (group NPDR). 80 patients with diabetes mellitus without retinopathy (NDR) were enrolled in DR group at the same period, another 80 healthy subjects (control group) were selected as control group. The plasma miR-126 level of all subjects was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The enzyme linked im-munosorbent assay (ELISA) method was used to detect plasma VEGF level. The clinical diagnostic value of miR-126 and VEGF in PDR patients was further analyzed. Results Plasma levels of miR-126 in PDR group, NPDR group and NDR group were lower than those in control group (P<0.05), PDR group was lower than NPDR group and NDR group (P<0.05); plasma levels of VEGF in PDR group, NPDR group and NDR group were higher than those in control group (P<0.05), PDR group was higher than NPDR group and NDR group (P<0.05). Total cholesterol (TC), triglyceride (TG) and glycated hemoglobin (HbA1c) in PDR group were higher than those in NPDR group and NDR group (P<0.05), low density lipoprotein cholesterol (LDL-C) in PDR group, NPDR group and NDR group were higher than those in control group (P<0.05), and LDL-C in PDR group was higher than that in NPDR group and NDR group (P<0.05). High density lipoprotein cholesterol (HDL-C) in PDR group and NDR group was lower than that in control group (P<0.05), C-reactive protein (CRP) in PDR group, NPDR group and NDR group was higher than that in control group (P<0.05); plasma miR-126 levels in PDR group were negatively correlated with TC, LDL-C, CRP and HbA1c (P<0.05), but positively correlated with HDL-C (P<0.05), and no correlation with TG; the plasma levels of VEGF in PDR patients were positively correlated with TC, TG, LDL-C, CRP and HbA1c (P<0.05), but negatively correlated with the expressions of miR-126 (r=-0.573, P=0.000); the AUC of miR-126 was 0.861, and when the cut-off value was <0.64, the diagnostic sensitivity and specificity were 82.50% , 83.64%; the area under curve (AUC) of VEGF was 0.889, and when the cut-off value was <7.000, the sensitivity and specificity of diagnosis were 82.73%, 86.25%; 0.847 for the AUC of HbA1c, and the sensitivity and specificity 81.82%, 87.50% respectively. Conclusions Plasma miR-126 is low-expressed and VEGF is high-expressed in PDR patients, there is a negative correlation between the two indexes. They may be involved in the course of PDR through abnormal lipid metabolism and inflammatory reaction and may be a potential biomarker for early diagnosis of PDR. Key words: Diabetic retinopathy/BL; MicroRNAs/BL; Vascular endothelial growth factors/BL