This paper proposes a novel chronically evaluated highest instantaneous priority next processor scheduling algorithm. The currently existing algorithms like first come first serve, shortest job first, round-robin, sho...This paper proposes a novel chronically evaluated highest instantaneous priority next processor scheduling algorithm. The currently existing algorithms like first come first serve, shortest job first, round-robin, shortest remaining time first, highest response ratio next and varying response ratio priority algorithm have some problems associated with them. Some of them can lead to endless waiting or starvation and some of them like round-robin has problem of too many context switches and high waiting time associated with them. In the proposed algorithm, we have taken care of all such problems. As the novel algorithm is capable of achieving as good results as shortest remaining time first algorithm and also it will never lead to starvation.展开更多
Serenity is an emotional experience that contributes to the acceptance of a situation. One phenomenon in the care of chronically ill older patients and patients in end of life care is that too much focus is placed on ...Serenity is an emotional experience that contributes to the acceptance of a situation. One phenomenon in the care of chronically ill older patients and patients in end of life care is that too much focus is placed on the patient’s disease. This can contribute to anxiety, sadness or sense of isolation. For older people that are chronically ill or in care at the end of life, it is important that the registered nurse can help them to find serenity. Further knowledge is needed about how the concept of serenity is used in relation to the care of older chronically ill patients. Aim: The purpose of this concept analysis was to clarify how serenity is used in nursing and in relation to the care of chronically ill older patients. Method: The study follows Rodgers’ evolutionary method of concept analysis. Findings: Serenity is a state of physical, mental, emotional and spiritual balance when life conditions can be managed or accepted. Through the experience of serenity the chronically ill older patient is able to find or develop the self in order to continue with dignity. The concept is most used at the lowest described levels of the self, including a perception of personal safety. The highest level involves a sense of wholeness and awareness. Conclusion: The concept of serenity is used in relation to chronically ill older patients as a condition where the patient finds balance and thus can manage or accept their situation. Chronically ill older patients will not recover. For that reason it needed a better understanding about what factors to experience serenity are needed. Further research is also needed to examine how registered nurses can support older chronically patients in finding serenity with the help of nursing interventions.展开更多
Background: Despite worsening health the chronically ill oldest older persons have expressed feelings of inner strength, which can be understood as resilience. The objective was to describe and compare the characteris...Background: Despite worsening health the chronically ill oldest older persons have expressed feelings of inner strength, which can be understood as resilience. The objective was to describe and compare the characteristics of resilience in two different age groups of chronically ill oldest older persons living at home and who needed help from home nursing care. Design: Cross-sectional design was used to describe and compare the resilience qualities between the two age groups. Methods: The inclusion criteria were 80 years or older, living at home with chronic disease, receiving help from home nursing care, and with the capacity to be interviewed. A sample of 120 oldest older women (n = 79) and men (n = 41) separated in two age groups, aged 80- 89 and 90+ years, participated in the study. Resilience characteristics were measured by Resilience Scale. Results: The whole group of oldest older people was vulnerable in relation to the characteristics of perseverance, self-reliance, and existential aloneness. Despite reduced physical health they reported a meaningful life, and equanimity. Even if there were no significant differences between the age groups among the oldest older persons in the characteristics of Resilience Scale (RS), in the characteristic of meaning there was a tendency of interaction between age and how much help from home nursing care the participants received. Conclusions: It is important to focus on the individual aging and the risk of developing illness and disabilities rather than focusing on chronologic age. Possessing meaning in life and equanimity may be strengths to meet challenges through illness and growing older.展开更多
AIM:To investigate the effect of Simotang(Decoction of Four Powered Drugs) on gastrointestinal motility,motilin and cholecystokinin expression in chronically stressed mice.METHODS:Forty mice were randomly divided into...AIM:To investigate the effect of Simotang(Decoction of Four Powered Drugs) on gastrointestinal motility,motilin and cholecystokinin expression in chronically stressed mice.METHODS:Forty mice were randomly divided into control group,stress group(model group),mosapride group and Simotang group,10 in each group.A variety of unpredictable stimulations were used to induce chronic stress in mice.Then,the mice were treated with distilled water,mosapride or Simotang for 7 d.Gastric emptying and intestinal propulsion function were detected.Serum level of motilin was measured by enzyme-linked immunosorbent assay.Expression of cholecystokinin(CCK) in intestine,spinal cord and brain of mice was detected by immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction,respectively.RESULTS:Simotang improved the gastric emptying and intestinal propulsion in chronically stressed mice.Furthermore,the serum motilin level was significantly higher and the expression levels of CCK-positive cells and genes were significantly lower in intestine,spinal cord and brain of Simotang group than in those of model group(P<0.05).No significant difference was found in serum motilin level and expression levels of CCK-positive cells and genes between the mosapride and Simotang groups.CONCLUSION:Simotang enhances the gastrointestinal motility in chronically stressed mice by regulating the serum motilin level and the expression of cholecystokinin.展开更多
Aim： To assess the effect of estradiol-17β （E2） and bisphenol A （BPA） administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups＇ reproductive system in ICR mice. Met...Aim： To assess the effect of estradiol-17β （E2） and bisphenol A （BPA） administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups＇ reproductive system in ICR mice. Methods： Female mice were implanted with a tube filled with 10 ng, 500 ng, 1 μg, or 10 μg of E2, or 100 μg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E2 was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 μg/day. Results： Most of the mice given 1 μg and 10 lag of E2 did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights （testes, epididymides and accessory reproductive glands） in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E2 and 5 mg of BPA than that in the control. Conclusion： Chronic exposure to E2 and BPA might disrupt spermatogenesis in male pups. （Asian JAndrol 2008 Mar; 10： 271-276）展开更多
AIM:To evaluate the effect of chronic mild stress(CMS) on the emergence of gastric ulcers and possible modulation by octreotide,a synthetic somatostatin analogue. METHODS:Adult male Wistar rats were subjected to nine ...AIM:To evaluate the effect of chronic mild stress(CMS) on the emergence of gastric ulcers and possible modulation by octreotide,a synthetic somatostatin analogue. METHODS:Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d,a multifactorial interactional animal model for CMS.Octreotide was administered daily for 21 d at two dose levels(50 and 90μg/kg)before exposure to stress procedure.Macro-and microscopical assessments were made,in addition to quantification of plasma corticosterone and gastric mucosal inflammatory,oxidative stress, and apoptotic biomarkers. RESULTS:Exposure to CMS elevated plasma corticosterone(28.3±0.6μg/dL,P=0.002),an event that was accompanied by gastric lesions(6.4±0.16 mm,P=0.01) and confirmed histopathologically.Moreover,the insult elevated gastric mucosal lipid peroxides(13±0.5 nmol/g tissue,P=0.001),tumor necrosis factor-α(3008.6±78.18 pg/g tissue,P<0.001),prostaglandin E2(117.1 ±4.31 pg/g tissue,P=0.002),and caspase-3 activity (2.4±0.14 OD/mg protein,P=0.002).Conversely,CMS mitigated interleukin-10(627.9±12.82 pg/g tissue,P= 0.001).Furthermore,in animals exposed to CMS,octreotide restored plasma corticosterone(61%and 71%from CMS,P=0.002)at both dose levels.These beneficial effects were associated with a remarkable suppression of gastric lesions(38%and 9%from CMS,P=0.01)and reversal of derangements in gastric mucosa. CONCLUSION:The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant,anti-inflammatory,and anti-apoptotic actions.展开更多
AIM To investigate the impact of IL28 B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODS We enrolled 52 children(between the ages of 4 and 18) with hepatitis B ...AIM To investigate the impact of IL28 B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODS We enrolled 52 children(between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B(CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1(rs1131476), OAS2(rs1293747),OAS3(rs2072136), OASL(rs10849829) and IL28B(rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus(HBV) DNA level < 2000 IU/m L and normalization of ALT activity(< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response(PR) and a complete response(CR) upon measurement at the 24-wk posttreatment follow-up. RESULTS The PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response(partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown(P < 0.05). The allele association analysis revealed that only the IL-28 B rs12979860(C vs T) and IL28 B rs12980275(A vs G) markers significantly affected the achievement of PR(P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28 B rs12980275 was significantly associated with PR(AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28 B rs12979860 was present only in the no-CR group(P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the noCR group(P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype(P = 0.0002 and P = 0.001, respectively), but no association with IL28 B haplotype was observed.CONCLUSION IL28 B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.展开更多
Objective: To validate a Greek version of the structured self-reported 8-item Morisky Medication Adherence Scale (MMAS-8) and determine its psychometric properties in patients with chronic illnesses. Methods: A cross-...Objective: To validate a Greek version of the structured self-reported 8-item Morisky Medication Adherence Scale (MMAS-8) and determine its psychometric properties in patients with chronic illnesses. Methods: A cross-sectional survey was conducted in a small public hospital and a public health care centre, in a rural town in western Greece. The sample consisted of 100 patients with various chronic illnesses. Data were collected between January-May 2011, on the Greek version of the MMAS-8 and Beliefs about Medicines Questionnaire (BMQ). Results: Scale’s reliability analysis revealed an overall Cronbach’s alpha of 0.753 and the corrected item to total correlations, were greater than 0.30 for each of the 8 items comprising the medication adherence scale, showing good internal consistency. Convergent validity was supported by a significant correlation between the present scale’s total score and the BMQ-Specific Necessity score (Spearman’s rho = 0.492, p < 0.001). Conclusion: The current study showed acceptable reliability and validity of the Greek version of the 8-item MMAS to measure adherence to medications for various chronic illnesses. The validated Greek version of the MMAS-8 can help towards understanding adherence barriers in Greece so as to develop effective strategies to increase adherence and reduce the costs.展开更多
The object of this study is to investigate the effect of VIP on pulmonary artery of chronically hypoxic rats. It was shown that chronic hypoxia depressed significantly pulmonary artery relaxation induced by VIP as com...The object of this study is to investigate the effect of VIP on pulmonary artery of chronically hypoxic rats. It was shown that chronic hypoxia depressed significantly pulmonary artery relaxation induced by VIP as compared with those of control (P<0. 001). The vascular relaxation of both groups was correlated with concentration of VIP. In addition, the relaxant effect of VIP on pulmonary arteries in rats was endothelium─independent, and was not prevented by indomethacin or nordihydroguaiaretic acid, but was abolished completely by methylene blue. These results suggest that the lower relaxation of pulmonary artery in rats might not be due to the endothelial injury caused by chronic hypoxia, and chronic hypoxia may inhibit directly the soluble guanylate cyclase in vascular smooth muscle cells invloved in synthesis of cGMP and thus reduced the sensitivity and reactivity of pulmonary artery to VIP.展开更多
The author has treated almost 400 chronically depressed outpatients during his career. He has also participated as a Field Trial Coordinator in the Unipolar Field Trials of DSM-IV and consulted with the DSM-V Mood Dis...The author has treated almost 400 chronically depressed outpatients during his career. He has also participated as a Field Trial Coordinator in the Unipolar Field Trials of DSM-IV and consulted with the DSM-V Mood Disorders Workgroup concerning his research for the new diagnostic nomenclature for the chronic depressions, Chronic Depression Disorder. In addition, he has served as Principal Investigator in several large clinical trials involving 2200 chronically depressed outpatients. The current paper is a Brief Report describing his negative reactions to the way 40 of his chronically depressed patients have been treated today by both Psychologists and Psychiatrists. All the patients are his patients and have been seen by him in psychotherapy over the past decade. Several reasons are proposed for the inadequate treatment and specific proposals are made for the improvement of treatment for the early-onset chronically depressed patient.展开更多
Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The asse...Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.展开更多
Currently,the diagnostic strategy for chronic gastritis(CG)is aimed not just at fixing the presence of gastric mucosal inflammation,but also at gastric cancer(GC)risk stratification in a particular patient.Modern clas...Currently,the diagnostic strategy for chronic gastritis(CG)is aimed not just at fixing the presence of gastric mucosal inflammation,but also at gastric cancer(GC)risk stratification in a particular patient.Modern classification approach with the definition of the stage of gastritis determines the need,activities and frequency of dynamic monitoring of a patient.However,this attitude to the patient suffering from CG was far from always.The present publication is a literature review describing the key milestones in the history of CG research,from the description of the first observations of inflammation of the gastric mucosa,assessment of gastritis as a predominantly functional disease,to the advent of endoscopy of the upper digestive tract and diagnostic gastric biopsy,assessment of the role of Helicobacter pylori infection in progression of inflammatory changes to atrophy,intestinal metaplasia,dysplasia and GC.展开更多
Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental ...Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.展开更多
Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice ...Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.展开更多
Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with...Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with CKD and its subtypes in China.Methods:The study included 475,376 adults from the China Kadoorie Biobank aged 30-79 years during 2004-2008 at baseline.An interviewer-administered questionnaire was used to collect the information about PA,which was quantified as metabolic equivalent of task hours per day(MET-h/day)and categorized into 4 groups based on quartiles.Cox regression was used to analyze the association between PA and CKD risk.Results:During a median follow-up of 12.1 years,5415 incident CKD cases were documented,including 1159 incident diabetic kidney disease(DKD)cases and 362 incident hypertensive nephropathy(HTN)cases.Total PA was inversely associated with CKD risk,with an adjusted hazard ratio(HR,95%confidence interval(95%CI))of 0.83(0.75-0.92)for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile.Similar results were observed for risk of DKD and HTN,and the corresponding HRs(95%CIs)were 0.75(0.58-0.97)for DKD risk and 0.56(0.37-0.85)for HTN risk.Increased nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD,with HRs(95%CIs)of 0.80(0.73-0.88),0.85(0.77-0.94),and 0.85(0.76-0.95)in the highest quartile,respectively.Conclusion:PA,including nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA,was inversely associated with the risk of CKD,including DKD,HTN,and other CKD,and such associations were dose dependent.展开更多
Background:Hemodialysis(HD) per se is a risk factor for thrombosis.Considering the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the...Background:Hemodialysis(HD) per se is a risk factor for thrombosis.Considering the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model.The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise(RE) with BFR on this molecule.Methods:Two hundred and six HD patients volunteered for this study(all with a glomerular filtration rate of <15 mL/min/1.73 m2).The RE+BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD(intradialytic exercise).RE repetitions included concentric and eccentric lifting phases(each lasting 2 s) and were supervised by a strength and conditioning specialist.Results:Several variables were associated with elevated levels of D-dimer,including higher blood glucose,citrate use,recent cardiovascular events,recent intercurrents,higher inflammatory status,catheter as vascular access,older patients(>70 years old),and HD vintage.Furthermore,RE+BFR significantly increases D-dimer after 4 h.Patients with borderline baseline D-dimer levels(400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range(≥500 ng/mL).Conclusion:These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE+BFR.D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE+BFR.展开更多
BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To ex...BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in China.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.展开更多
Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we id...Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.展开更多
Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanis...Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.展开更多
Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial ac...Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.展开更多
文摘This paper proposes a novel chronically evaluated highest instantaneous priority next processor scheduling algorithm. The currently existing algorithms like first come first serve, shortest job first, round-robin, shortest remaining time first, highest response ratio next and varying response ratio priority algorithm have some problems associated with them. Some of them can lead to endless waiting or starvation and some of them like round-robin has problem of too many context switches and high waiting time associated with them. In the proposed algorithm, we have taken care of all such problems. As the novel algorithm is capable of achieving as good results as shortest remaining time first algorithm and also it will never lead to starvation.
文摘Serenity is an emotional experience that contributes to the acceptance of a situation. One phenomenon in the care of chronically ill older patients and patients in end of life care is that too much focus is placed on the patient’s disease. This can contribute to anxiety, sadness or sense of isolation. For older people that are chronically ill or in care at the end of life, it is important that the registered nurse can help them to find serenity. Further knowledge is needed about how the concept of serenity is used in relation to the care of older chronically ill patients. Aim: The purpose of this concept analysis was to clarify how serenity is used in nursing and in relation to the care of chronically ill older patients. Method: The study follows Rodgers’ evolutionary method of concept analysis. Findings: Serenity is a state of physical, mental, emotional and spiritual balance when life conditions can be managed or accepted. Through the experience of serenity the chronically ill older patient is able to find or develop the self in order to continue with dignity. The concept is most used at the lowest described levels of the self, including a perception of personal safety. The highest level involves a sense of wholeness and awareness. Conclusion: The concept of serenity is used in relation to chronically ill older patients as a condition where the patient finds balance and thus can manage or accept their situation. Chronically ill older patients will not recover. For that reason it needed a better understanding about what factors to experience serenity are needed. Further research is also needed to examine how registered nurses can support older chronically patients in finding serenity with the help of nursing interventions.
基金Nord-Trøndelag University College (pro- ject number 24006)
文摘Background: Despite worsening health the chronically ill oldest older persons have expressed feelings of inner strength, which can be understood as resilience. The objective was to describe and compare the characteristics of resilience in two different age groups of chronically ill oldest older persons living at home and who needed help from home nursing care. Design: Cross-sectional design was used to describe and compare the resilience qualities between the two age groups. Methods: The inclusion criteria were 80 years or older, living at home with chronic disease, receiving help from home nursing care, and with the capacity to be interviewed. A sample of 120 oldest older women (n = 79) and men (n = 41) separated in two age groups, aged 80- 89 and 90+ years, participated in the study. Resilience characteristics were measured by Resilience Scale. Results: The whole group of oldest older people was vulnerable in relation to the characteristics of perseverance, self-reliance, and existential aloneness. Despite reduced physical health they reported a meaningful life, and equanimity. Even if there were no significant differences between the age groups among the oldest older persons in the characteristics of Resilience Scale (RS), in the characteristic of meaning there was a tendency of interaction between age and how much help from home nursing care the participants received. Conclusions: It is important to focus on the individual aging and the risk of developing illness and disabilities rather than focusing on chronologic age. Possessing meaning in life and equanimity may be strengths to meet challenges through illness and growing older.
基金Supported by The National Key Basic Research(973) Program, No.2009CB523002the Hunan Provincial TCM Research Fund,China,No.209004
文摘AIM:To investigate the effect of Simotang(Decoction of Four Powered Drugs) on gastrointestinal motility,motilin and cholecystokinin expression in chronically stressed mice.METHODS:Forty mice were randomly divided into control group,stress group(model group),mosapride group and Simotang group,10 in each group.A variety of unpredictable stimulations were used to induce chronic stress in mice.Then,the mice were treated with distilled water,mosapride or Simotang for 7 d.Gastric emptying and intestinal propulsion function were detected.Serum level of motilin was measured by enzyme-linked immunosorbent assay.Expression of cholecystokinin(CCK) in intestine,spinal cord and brain of mice was detected by immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction,respectively.RESULTS:Simotang improved the gastric emptying and intestinal propulsion in chronically stressed mice.Furthermore,the serum motilin level was significantly higher and the expression levels of CCK-positive cells and genes were significantly lower in intestine,spinal cord and brain of Simotang group than in those of model group(P<0.05).No significant difference was found in serum motilin level and expression levels of CCK-positive cells and genes between the mosapride and Simotang groups.CONCLUSION:Simotang enhances the gastrointestinal motility in chronically stressed mice by regulating the serum motilin level and the expression of cholecystokinin.
文摘Aim： To assess the effect of estradiol-17β （E2） and bisphenol A （BPA） administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups＇ reproductive system in ICR mice. Methods： Female mice were implanted with a tube filled with 10 ng, 500 ng, 1 μg, or 10 μg of E2, or 100 μg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E2 was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 μg/day. Results： Most of the mice given 1 μg and 10 lag of E2 did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights （testes, epididymides and accessory reproductive glands） in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E2 and 5 mg of BPA than that in the control. Conclusion： Chronic exposure to E2 and BPA might disrupt spermatogenesis in male pups. （Asian JAndrol 2008 Mar; 10： 271-276）
文摘AIM:To evaluate the effect of chronic mild stress(CMS) on the emergence of gastric ulcers and possible modulation by octreotide,a synthetic somatostatin analogue. METHODS:Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d,a multifactorial interactional animal model for CMS.Octreotide was administered daily for 21 d at two dose levels(50 and 90μg/kg)before exposure to stress procedure.Macro-and microscopical assessments were made,in addition to quantification of plasma corticosterone and gastric mucosal inflammatory,oxidative stress, and apoptotic biomarkers. RESULTS:Exposure to CMS elevated plasma corticosterone(28.3±0.6μg/dL,P=0.002),an event that was accompanied by gastric lesions(6.4±0.16 mm,P=0.01) and confirmed histopathologically.Moreover,the insult elevated gastric mucosal lipid peroxides(13±0.5 nmol/g tissue,P=0.001),tumor necrosis factor-α(3008.6±78.18 pg/g tissue,P<0.001),prostaglandin E2(117.1 ±4.31 pg/g tissue,P=0.002),and caspase-3 activity (2.4±0.14 OD/mg protein,P=0.002).Conversely,CMS mitigated interleukin-10(627.9±12.82 pg/g tissue,P= 0.001).Furthermore,in animals exposed to CMS,octreotide restored plasma corticosterone(61%and 71%from CMS,P=0.002)at both dose levels.These beneficial effects were associated with a remarkable suppression of gastric lesions(38%and 9%from CMS,P=0.01)and reversal of derangements in gastric mucosa. CONCLUSION:The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant,anti-inflammatory,and anti-apoptotic actions.
文摘AIM To investigate the impact of IL28 B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODS We enrolled 52 children(between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B(CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1(rs1131476), OAS2(rs1293747),OAS3(rs2072136), OASL(rs10849829) and IL28B(rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus(HBV) DNA level < 2000 IU/m L and normalization of ALT activity(< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response(PR) and a complete response(CR) upon measurement at the 24-wk posttreatment follow-up. RESULTS The PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response(partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown(P < 0.05). The allele association analysis revealed that only the IL-28 B rs12979860(C vs T) and IL28 B rs12980275(A vs G) markers significantly affected the achievement of PR(P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28 B rs12980275 was significantly associated with PR(AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28 B rs12979860 was present only in the no-CR group(P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the noCR group(P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype(P = 0.0002 and P = 0.001, respectively), but no association with IL28 B haplotype was observed.CONCLUSION IL28 B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.
文摘Objective: To validate a Greek version of the structured self-reported 8-item Morisky Medication Adherence Scale (MMAS-8) and determine its psychometric properties in patients with chronic illnesses. Methods: A cross-sectional survey was conducted in a small public hospital and a public health care centre, in a rural town in western Greece. The sample consisted of 100 patients with various chronic illnesses. Data were collected between January-May 2011, on the Greek version of the MMAS-8 and Beliefs about Medicines Questionnaire (BMQ). Results: Scale’s reliability analysis revealed an overall Cronbach’s alpha of 0.753 and the corrected item to total correlations, were greater than 0.30 for each of the 8 items comprising the medication adherence scale, showing good internal consistency. Convergent validity was supported by a significant correlation between the present scale’s total score and the BMQ-Specific Necessity score (Spearman’s rho = 0.492, p < 0.001). Conclusion: The current study showed acceptable reliability and validity of the Greek version of the 8-item MMAS to measure adherence to medications for various chronic illnesses. The validated Greek version of the MMAS-8 can help towards understanding adherence barriers in Greece so as to develop effective strategies to increase adherence and reduce the costs.
文摘The object of this study is to investigate the effect of VIP on pulmonary artery of chronically hypoxic rats. It was shown that chronic hypoxia depressed significantly pulmonary artery relaxation induced by VIP as compared with those of control (P<0. 001). The vascular relaxation of both groups was correlated with concentration of VIP. In addition, the relaxant effect of VIP on pulmonary arteries in rats was endothelium─independent, and was not prevented by indomethacin or nordihydroguaiaretic acid, but was abolished completely by methylene blue. These results suggest that the lower relaxation of pulmonary artery in rats might not be due to the endothelial injury caused by chronic hypoxia, and chronic hypoxia may inhibit directly the soluble guanylate cyclase in vascular smooth muscle cells invloved in synthesis of cGMP and thus reduced the sensitivity and reactivity of pulmonary artery to VIP.
文摘The author has treated almost 400 chronically depressed outpatients during his career. He has also participated as a Field Trial Coordinator in the Unipolar Field Trials of DSM-IV and consulted with the DSM-V Mood Disorders Workgroup concerning his research for the new diagnostic nomenclature for the chronic depressions, Chronic Depression Disorder. In addition, he has served as Principal Investigator in several large clinical trials involving 2200 chronically depressed outpatients. The current paper is a Brief Report describing his negative reactions to the way 40 of his chronically depressed patients have been treated today by both Psychologists and Psychiatrists. All the patients are his patients and have been seen by him in psychotherapy over the past decade. Several reasons are proposed for the inadequate treatment and specific proposals are made for the improvement of treatment for the early-onset chronically depressed patient.
文摘Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.
文摘Currently,the diagnostic strategy for chronic gastritis(CG)is aimed not just at fixing the presence of gastric mucosal inflammation,but also at gastric cancer(GC)risk stratification in a particular patient.Modern classification approach with the definition of the stage of gastritis determines the need,activities and frequency of dynamic monitoring of a patient.However,this attitude to the patient suffering from CG was far from always.The present publication is a literature review describing the key milestones in the history of CG research,from the description of the first observations of inflammation of the gastric mucosa,assessment of gastritis as a predominantly functional disease,to the advent of endoscopy of the upper digestive tract and diagnostic gastric biopsy,assessment of the role of Helicobacter pylori infection in progression of inflammatory changes to atrophy,intestinal metaplasia,dysplasia and GC.
基金supported by the National Natural Science Foundation of China,Nos.82071190 and 82371438(to LC)Innovative Strong School Project of Guangdong Medical University,No.4SG21230G(to LC)Scientific Research Foundation of Guangdong Medical University,No.GDMUM2020017(to CL)。
文摘Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.
基金supported financially by the National Natural Science Foundation of China,No.82071272(to YZ).
文摘Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.
基金supported by National Natural Science Foundation of China(82192900,82192901,82192904,81941018,and 91846303)Peking University Medicine Seed Fund for Interdisciplinary Research(BMU2022MX025)+5 种基金the Fundamental Research Funds for the Central Universitiessupported by a grant from the Kadoorie Charitable Foundation in Hong Kongsupported by grants from the UK Wellcome Trust(212946/Z/18/Z,202922/Z/16/Z,104085/Z/14/Z,and 088158/Z/09/Z)the National Key R&D Program of China(2016YFC0900500)National Natural Science Foundation of China(81390540)Chinese Ministry of Science and Technology(2011BAI09B01)。
文摘Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with CKD and its subtypes in China.Methods:The study included 475,376 adults from the China Kadoorie Biobank aged 30-79 years during 2004-2008 at baseline.An interviewer-administered questionnaire was used to collect the information about PA,which was quantified as metabolic equivalent of task hours per day(MET-h/day)and categorized into 4 groups based on quartiles.Cox regression was used to analyze the association between PA and CKD risk.Results:During a median follow-up of 12.1 years,5415 incident CKD cases were documented,including 1159 incident diabetic kidney disease(DKD)cases and 362 incident hypertensive nephropathy(HTN)cases.Total PA was inversely associated with CKD risk,with an adjusted hazard ratio(HR,95%confidence interval(95%CI))of 0.83(0.75-0.92)for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile.Similar results were observed for risk of DKD and HTN,and the corresponding HRs(95%CIs)were 0.75(0.58-0.97)for DKD risk and 0.56(0.37-0.85)for HTN risk.Increased nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD,with HRs(95%CIs)of 0.80(0.73-0.88),0.85(0.77-0.94),and 0.85(0.76-0.95)in the highest quartile,respectively.Conclusion:PA,including nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA,was inversely associated with the risk of CKD,including DKD,HTN,and other CKD,and such associations were dose dependent.
基金supported by a grant provided by the Coordenacao de Aperfeicoamento de Pessoal de Nível Superior-Brazil-Finance Code 001 and National Council for Scientific and Technological Developmentfinanced in part by the Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil--Finance Code 001funded by the Fundacao de Apoio à Pesquisa do Distrito Federal with grants from demanda espontanea-Edital 09/2022
文摘Background:Hemodialysis(HD) per se is a risk factor for thrombosis.Considering the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model.The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise(RE) with BFR on this molecule.Methods:Two hundred and six HD patients volunteered for this study(all with a glomerular filtration rate of <15 mL/min/1.73 m2).The RE+BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD(intradialytic exercise).RE repetitions included concentric and eccentric lifting phases(each lasting 2 s) and were supervised by a strength and conditioning specialist.Results:Several variables were associated with elevated levels of D-dimer,including higher blood glucose,citrate use,recent cardiovascular events,recent intercurrents,higher inflammatory status,catheter as vascular access,older patients(>70 years old),and HD vintage.Furthermore,RE+BFR significantly increases D-dimer after 4 h.Patients with borderline baseline D-dimer levels(400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range(≥500 ng/mL).Conclusion:These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE+BFR.D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE+BFR.
基金the National Key Clinical Specialty Construction Project,No.ZK108000CAMS Innovation Fund for Medical Sciences,No.2021-I2M-C&T-A-001 and No.2022-I2M-C&T-B-012.
文摘BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in China.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.
基金National Natural Science Foundation of China(81870850)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX23_0322)。
文摘Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.
基金financially supported by Shenzhen Agricultural Development Special Fund(Fishery)Agricultural High-Tech Project([2021]735)the Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173207022)Youth Science Foundation Project(32101936)。
文摘Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.
基金supported by Canadian Institutes for Health Research (CIHR)(to ADR and WW)Ontario Graduate Scholarship (to NOB)+2 种基金Alzheimer's Society of CanadaHeart and Stroke Foundation of Canada,CIHRthe Canadian Consortium for Neurodegeneration and Aging (CCNA)(to SNW)。
文摘Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.
