Non-coding RNAs in acute ischemic stroke:from brain to periphery

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Reactive oxygen species and oxidative stress in acute pancreatitis:Pathogenesis and new therapeutic interventions

Acute pancreatitis(AP)is a common acute gastrointestinal disorder affecting approximately 20%of patients with systemic inflammatory responses that may cause pancreatic and peripancreatic fat necrosis.This condition often progresses to multiple organ failure,significantly increasing morbidity and mortality.Oxidative stress,characterized by an imbalance between the body’s reactive oxygen species(ROS)and antioxidants,activates the inflammatory signaling pathways.Although the pathogenesis of AP is not fully understood,ROS are increasingly recognized as critical in the disease's progression and development.Modulating the oxidative stress pathway has shown efficacy in mitigating the progression of AP.Despite numerous basic studies examining this pathway,comprehensive reviews of recent research remain sparse.This systematic review offers an in-depth examination of the critical role of oxidative stress in the pathogenesis and progression of AP and evaluates the therapeutic potential of antioxidant interventions in its management.

The effect of Huanglian Jiedu Decoction on inflammatory factors and oxidative stress in patients with acute ischemic stroke

Objective:To study the clinical efficacy of Huanglian Jiedu decoction in treating acute ischemic stroke(AIS)and its effects on inflammatory factors and oxidative stress.Method:A total of 53 patients with AIS were recruited as the study subjects and randomly divided into a control group and a treatment group using a random number table method.The control group consisted of 26 patients and the treatment group consisted of 27 patients.The control group received conventional Western medicine treatment.The control group received routine Western medicine treatment,while the treatment group received Huanglian Jiedu decoction based on the control group,with 14 days as a course of treatment.The effects of Huanglian Jiedu decoction on neurological function and activities of daily living were evaluated using the National Institute of Health stroke scale(NIHSS)and activities of daily living(ADL)scores.The effects of Huanglian Jiedu decoction on inflammatory reactions and oxidative stress were evaluated by detecting interleukin-4(IL-4),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),transforming growth factorβ(TGF-β),total antioxidative capacity(T-AOC),malondialdehyde(MDA),superoxide dismutase(SOD),and catalase(CAT)levels.Results:After treatment with Huanglian Jiedu Decoction,the ALD scores of AIS patients in both groups increased,while the NISHH scores decreased,suggesting that Huanglian Jiedu Decoction has therapeutic effects on AIS patients.It also reduces the levels of serum IL-6,TNF-α,MDA in AIS patients and increases the levels of IL-4,TGF-β,CAT,SOD,T-AOC,suggesting that Huanglian Jiedu decoction can improve the anti-inflammatory and antioxidant abilities of AIS patients.Conclusion:Huanglian Jiedu decoction can help AIS patients recover their neurological function,increase their capacity for self-care in daily life,and strengthen the body’s anti-inflammatory and antioxidant defenses.

Effect of Acute Low Temperature Stress on Oxygen Consumption Rate and Respiration Frequency in Silurus meridionalis and Pelteobag vachelli

The objective of the study was to explore the effect of acute low temperature stress on VO2 and Vf of Silurus meridionalis and Pelteobag vachelli after 10 minutes cold water bath with different temperature.The investigation was operated under the temperature of 24 ℃.It was found that the VO2 and Vf of Silurus meridionalis after 6 and 0 ℃ stress showed a decrease-increase-decrease trend while other groups showed a rapid increase then slowly recovery trend.The VO2 and Vf of Pelteobag vachelli after 0 ℃stress showed a decrease-increase-decrease trend while other groups showed an increase then slowly recovery process.It was suggested that Pelteobag vachelli was more adaptive to acute cold stress,but it cost more energy adapting to cold stress compared to Silurus meridionalis.

Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

Irisin attenuates intestinal injury,oxidative and endoplasmic reticulum stress in mice with L-arginine-induced acute pancreatitis

BACKGROUND Acute pancreatitis(AP)is often associated with intestinal injury,which in turn exaggerates the progression of AP.Our recent study has shown that a low level of serum irisin,a novel exercise-induced hormone,is associated with poor outcomes in patients with AP and irisin administration protects against experimental AP.However,the role of irisin in intestinal injury in AP has not been evaluated.AIM To investigate the effect of irisin administration on intestinal injury in experimental AP.METHODS AP was induced in male adult mice by two hourly intraperitoneal injections of Larginine.At 2 h after the last injection of L-arginine,irisin(50 or 250μg/kg body weight)or 1 mL normal saline(vehicle)was administered through intraperitoneal injection.The animals were sacrificed at 72 h after the induction of AP.Intestinal injury,apoptosis,oxidative and endoplasmic reticulum(ER)stress were evaluated.RESULTS Administration of irisin significantly mitigated intestinal damage,reduced apoptosis,and attenuated oxidative and ER stress in AP mice.In addition,irisin treatment also effectively downregulated serum tumor necrosis factor-alpha and interleukin-6 levels and alleviated injury in the pancreas,liver and lung of AP mice.CONCLUSION Irisin-mediated multiple physiological events attenuate intestinal injury following an episode of AP.Irisin has a great potential to be further developed as an effective treatment for patients with AP.

Acute pancreatitis:The stress factor

Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications.Etiologies of pancreatitis vary,with gallstones accounting for the majority of all cases,followed by alcohol.Other causes of pancreatitis include trauma,ischemia,mechanical obstruction,infections,autoimmune,hereditary,and drugs.The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion,intracellular activation of proteases,and generation of inflammatory mediators.Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells,whose systemic action ultimately determined the severity of the disease.Indeed,severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome,characterized by a progressive physiologic failure of several interdependent organ systems.Stress occurs when homeostasis is threatened,and stressors can include physical or mental forces,or combinations of both.Depending on the timing and duration,stress can result in beneficial or harmful consequences.While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis,the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention.This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis.

Relationship between acute stress and sleep disorder in grass-root military personnel:Mediating effect of social support

Background: To explore the relationship between acute stress, social support and sleep disorder in grass-root military personnel, and construct the relational model through structural equation modeling. Methods: A total of 2,411 grass-root military personnel were randomly selected by cluster sampling, and administered the Chinese Military Personnel Sleep Disorder Scale, Military Acute Stress Scale and Social Support Rating Scale.Results: The total score of acute stress scale was positively correlated with the total score and factor scores of sleep disorder scale(r=0.209~0.465, P【0.01); The total score of social support scale was positively correlated with the total score of acute stress scale and the total score and factor scores of sleep disorder scale(r=0.356~0.537, P【0.01). The analysis of mediating effects showed that lack of social support partially mediated between acute stress and the factors of sleep disorder. The analysis of structural equation model showed that acute stress not only had a direct effect on sleep disorder(the path coefficient was 0.29, P=0.000), but also on lack of social support(the path coefficient was 0.39, P=0.000); lack of social support had a direct effect on sleep disorder(the path coefficient was 0.48, P=0.000).Conclusions: Acute stress and lack of social support are two significant factors of sleep disorder in grass-root military personnel. Well-established social support could alleviate sleep disorder induced by acute stress. Lack of social support was a partial mediator between acute stress and sleep disorder.

Stress granules inhibit endoplasmic reticulum stress-mediated apoptosis during hypoxia-induced injury in acute liver failure

BACKGROUND Stress granules(SGs)could be formed under different stimulation to inhibit cell injury.AIM To investigate whether SGs could protect hepatocytes from hypoxia-induced damage during acute liver failure(ALF)by reducing endoplasmic reticulum stress(ERS)mediated apoptosis.METHODS The agonist of SGs,arsenite(Ars)was used to intervene hypoxia-induced hepatocyte injury cellular model and ALF mice models.Further,the siRNA of activating transcription factor 4(ATF4)and SGs inhibitor anisomycin was then used to intervene in cell models.RESULTS With the increase of hypoxia time from 4 h to 12 h,the levels of HIF-1α,ERS and apoptosis gradually increased,and the expression of SGs marker G3BP1 and TIA-1 was increased and then decreased.Compared with the hypoxia cell model group and ALF mice model,the levels of HIF-1α,apoptosis and ERS were increased in the Ars intervention group.After siRNA-ATF4 intervention,the level of SGs in cells increased,and the levels of HIF-1α,ERS and apoptosis decreased.Compared with the siRNA-ATF4 group,the levels of G3BP1 in the siRNAATF4+anisomycin group were decreased,and the levels of HIF-1α,ERS and apoptosis were increased.Moreover,compared with the ALF group,the degree of liver injury and liver function,the levels of HIF-1α,ERS and apoptosis in the Ars intervention group were decreased,the level of SGs was increased.CONCLUSION SGs could protect hepatocytes from hypoxia-induced damage during ALF by reducing ERSmediated apoptosis.

Proteomic analysis of acute responses to copper sulfate stress in larvae of the brine shrimp,Artemia sinica

Proteomics was used to reveal the differential protein expression profiles of acute responses to copper sulfate exposure in larvae of Artemia sinica.Fourteen differentially displayed protein spots were detected and seven of them were identified.Three spots were up-expressed and identified:actin, heat shock protein 70,and chaperone subunit 1;three down-regulated proteins were identified:arginine kinase,elongation factor-2,and glycine-rich protein;and a newly expressed protein was identified as peroxiredoxin.The study indicates the involvement of all the differentially expressed proteins in the early responses of protein expression,and in the survival of A.sinica in the presence of copper and other heavy metals;the findings improve understanding of the organism’s adaptive responses and resistance.

Regulatory effects of hydrogen sulfide on alveolar epithelial cell endoplasmic reticulum stress in rats with acute lung injury

BACKGROUND: The present study was undertaken to examine the regulatory effect of hydrogen sulfide(H2S) on endoplasmic reticulum stress in alveolar epithelial cells of rats with acute lung injury(ALI) induced by oleic acid(OA).METHODS: Seventy-two male Sprague Dawley(SD) rats were divided into control group, oleic acid-induced ALI group(OA group), oleic acid-induced ALI with sodium hydrosulfide(Na HS) pretreatment group(OA+Na HS group), and sodium hydrosulfide treatment group(Na HS group). Rats of each group were further subdivided into 3 subgroups. Index of quantitative assessment of histological lung injury(IQA), wet/dry weight ratio(W/D) and H2 S level of lung tissues were measured. The expressions of endoplasmic reticulum stress markers including glucose-regulated protein 78(GRP78) and α-subunit of eukaryotic translation initiation factor-2(el F2α) in lung tissues were measured by immunohistochemical staining and Western blotting.RESULTS: The IQA score and W/D ratio of lung tissues at the three time points significantly increased in rats injected with OA, but significantly decreased in other rats injected with OA and Na HS. The level of H2 S in lung tissue at the three time points significantly decreased in rats injected with OA, but significantly increased in other rats injected with both OA and Na HS. GRP78 and el F2α decreased in rats injected with OA, but increased in other rats injected with both OA and Na HS, especially at 4-hour and 6-hour time points.CONCLUSION: The results suggested that H2 S could promote alveolar epithelial cell endoplasmic reticulum stress in rats with ALI.

The effects of large doses of vitamin C and vitamin E on nerve injury, neurotrophic and oxidative stress in patients with acute craniocerebral injury

Objective:To study the effects of large doses of vitamin C and vitamin E on nerve injury,neurotrophic and oxidative stress in patients with acute craniocercbral injury.Methods:Patients with acute cranioccrebral trauma who were admitted to the Third People's Hospital of Zigong from April 2014 to December 2016 were selected as the subjects and were randomly divided into two groups.The control group received conventional treatment,and the intervention group received large doses of vitamin C and vitamin E combined with conventional treatment.On the yh day and 7th day after treatment,peripheral blood was collected and serum was isolated,then the contents of nerve injury index NSE,S 100B,NGB,UCH-L1,Tf,Ft and neurotrophic indexes NTF-α,BDNE NGF and IGF-I were determined by Enzyme-linked immunosorbent assay kit,and the contents of SOD,GPx,CAT,OH-,O2,MDA and AOPP were measured by radioactive immunoprecipitation kit.Results:3th day and 7th day after treatment,the contents of NSE,S100B,NGB,UCH-L1,Tf,Ft,NTF-α,BDNF,NGF,IGF-Ⅰ,OH-,O2-,MDA and AOPP in the intervention group were all significantly lower than those in the control group.The content of SOD,GPx and CAT in serum in the intervention group was significantly higher than that in the control group.Conclusions:High-dose vitamin C and vitamin E treatment can alleviate nerve injury,oxidative stress response,and improve neurotrophic state in patients with acute craniocerebral injury.

Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field

Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however,its efficacy is limited in cases of advanced liver injury or when administered at a late stage.In the current study,we discovered that treatment with a moderate intensity static magnetic field(SMF)notably reduced the mortality rate in mice subjected to high-dose APAP from 40%to 0%,proving effective at both the initial liver injury stage and the subsequent recovery stage.During the early phase of liver injury,SMF markedly reduced APAPinduced oxidative stress,free radicals,and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery,application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation.Moreover,the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery,even 24 h post overdose,when the effectiveness of NAC alone substantially declines.Overall,this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose.Of note,this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP,and potentially other toxic overdoses.

Stroke:Evolution of newer treatment modalities for acute ischemic stroke

Acute ischemic stroke is one of the leading causes of morbidity and mortality worldwide.Restoration of cerebral blood flow to affected ischemic areas has been the cornerstone of therapy for patients for eligible patients as early diagnosis and treatment have shown improved outcomes.However,there has been a paradigm shift in the management approach over the last decade,and with the emphasis currently directed toward including newer modalities such as neuroprotection,stem cell treatment,magnetic stimulation,anti-apoptotic drugs,delayed recanali-zation,and utilization of artificial intelligence for early diagnosis and suggesting algorithm-based management protocols.

The Analysis of Wall Shear Stress Modulated by Acute Exercise in the Human Common Carotid Artery with an Elastic Tube Model

Assessment of the magnitude and pattern of wall shear stress(WSS)in vivo is the prerequisite for studying the quantitative relationship between exercise-induced WSS and arterial endothelial function.In the previous studies,the calculation of the WSS modulated by exercise training was primarily based upon the rigid tube model,which did not take non-linear effects of vessel elastic deformation into consideration.In this study,with an elastic tube model,we estimated the effect of a bout of 30-minute acute cycling exercise on the WSS and the flow rate in the common carotid artery according to the measured inner diameter,center-line blood flow velocity,heart rates and the brachial blood pressures before and after exercise training.Furthermore,the roles of exerciseinduced arterial diameter and blood flow rate in the change of WSS were also determined.The numerical results demonstrate that acute exercise significantly increases the magnitudes of blood flow rate and WSS.Moreover,the vessel elastic deformation is a non-negligible factor in the calculation of the WSS induced by exercise,which generates greater effects on the minimum WSS than the maximum WSS.Additionally,the contributions of exercise-induced variations in blood flow rate and diameter are almost identical in the change of the mean WSS.

Influence of standardized nursing intervention combined with mindfulness stress reduction training on the curative effect in patients with acute pancreatitis

BACKGROUND Acute pancreatitis(AP)is a common inflammatory disease of the pancreas with high mortality rates.It is of great significance to take scientific intervention measures for patients with AP in time.AIM To explore the effect of standardized nursing combined with mindfulness stress reduction training on the curative effect,negative emotion,and quality of life in patients with acute pancreatitis.METHODS A total of 80 patients with acute pancreatitis admitted to The First People's Hospital of Jiangxia District Hospital from May 2021 to May 2023 were randomly divided into control group and observation group(n=40).Patients in control group were given the standardized nursing intervention,and the observation group were given standardized nursing plus mindfulness stress reduction training intervention.The time of clinical symptom disappeared or improved,complication occurrence rate,emotional state,and quality of life score of the two groups were observed and compared.RESULTS In comparison with the control group,the bowel sound recovery time,ventosity and abdominal pain improvement time,and venting and cacation time in observation group were shorter,and the total incidence rate of complications was reduced,showing statistically significant difference(P<0.05).The scores of anxiety and depression in observation group were lower than those in control group(P<0.05).Serum levels of tumour necrosis factor alpha,interleukin(IL)-6,IL-1βand IL-8 in observation group were lower than those in control group(P<0.05).The scores of life quality in physiology,psychology,environment and social relations in observation group were higher than those in control group,and the differences were statistically significant(P<0.05).CONCLUSION The application of standardized nursing intervention combined with mindfulness stress reduction training in patients with acute pancreatitis has a definite effect,which can help to ameliorate the clinical symptoms,anxiety and depression of patients,reduce the incidence rate of complications,and improve the prognosis of patients.

Homocysteine and oxidative stress in acute stroke

Homocysteine is a sulfhydryl-containing amino acid derived from the essential amino acid methionine. Total Hcy plasma level varies in the range of 5-15 μmol/L in the normal population. Our aim in this study was to investigate the possible correlations among homocysteine plasma levels, oxidative stress parameters and clinical evolution of stroke. Fifty patients with large-vessel ischemic stroke were studied. Biochemical determinations were performed at entry (T0) and then repeated one month after stroke (T1). Homocysteine levels were significantly increased at T0 with respect to T1 and showed a significant positive correlation with the expression of oxidative stress markers and a negative correlation with indicators of protective anti stress activity. A significant increase of antioxidant activity occurred from T0 to T1 and changes were associated with the severity of clinical conditions. In particular, the extent of homocysteine and of oxidative stress markers plasmatic levels re- duction and of the contemporary increase in anti stress biochemical activities were associated with a reduction of NIHSS scores. These findings, besides confirming an involvement of oxidative stress in in- fluencing the evolution of stroke, suggest a role for homocysteine as a potentially modifiable biochemical alteration able to modulate some mechanisms in- volved in the production of ischemic damage.

Research Progress on the Pathogenesis of Acute Lung Injury(ALI)

In this review,the databases searched were PubMed and Web of Science.It is believed that the main causes of acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are inflammatory response disorders,excessive oxidative stress,cell death,endoplasmic reticulum stress,coagulation dysfunction,and weakened aquaporin function.

Effect of sub-acute exposure to TiO_2 nanoparticles on oxidative stress and histopathological changes in Juvenile Carp (Cyprinus carpio)

Increasing application of nanotechnology highlights the need to clarify and understand nanotoxicity. Mammalian and in vitro studies have raised concerns about the toxicity of titanium dioxide nanoparticles （TiO2-NPs）, but there are limited data on ecotoxicity to aquatic organisms. In this work, the sub-acute toxicity of TiO2-NPs to carp （Cyprinus carpio） was assessed. Superoxide dismutase （SOD）, catalase （CAT） and peroxidase （POD） activities and lipid peroxidation （LPO） levels in liver, gill and brain tissues of carps varied with concentration of TiO2-NPs suspensions and exposure time （up to 8 d）. As a result, 100 and 200 mg/L TiO2-NPs caused statistically significant decrease in SOD, CAT and POD activities and significant increase in LPO levels in tissues （P 〈 0.05）, suggesting that the fish exposed to these two concentrations of TiO2-NPs suffered from the oxidative stress. The extent of depletion of antioxidant enzymes activities and the elevation of LPO in the liver was the greatest, indicating that the liver might be the most susceptible organ to TiO2-NPs exposure. In addition, carps had gill pathologies including edema and thickening of gill lamellae as well as gill filaments, and liver pathologies including necrotic and apoptosis hepatocytes after exposed to 100 and 200 mg/L TiO2-NPs for 20 d. These results indicated a potential risk from TiO2-NPs released into the aqueous environment.

Protective effect of fermented papaya preparation on stress-induced acute gastric mucosal lesion

Stress ulceration is single or multiple mucosal defects with/without bleeding from the gastric mucosa during the physiologic stress. Oxidative stress (OS) is a key pathogenic factor in psychogenic stress-induced acute gastric mucosal lesion (AGML). Fermented papaya preparation (FPP) is reported to have oxygen radical scavenging activity and is effective in OS-related diseases. Here, we investigated the protective effects and the mechanism of action of FPP on stress-induced AGML in rats, induced by water immersion restraint stress (WIRS). Exposure of rats to 6-hour WIRS resulted in the appearance of splinter hemorrhages and mucosal lesions in the stomach. WIRS induced significant increase in lipid peroxidation and decrease in superoxide dismutase-like activity in both the plasma and gastric mucosa. WIRS also significantly increased myeloperoxidase activity together with Nuclear factor-kappaB (NF-kB) activation in gastric mucosa. FPP reduced all the above changes. The results suggest that oral administration of FPP provides protection against WIRS-induced acute gastric mucosal lesions through its anti-oxidative and anti-inflammatory properties.