Publications by authors named "Chun-Feng Liu"

299 Publications

Non-Coding RNAs: Master Regulators of Inflammasomes in Inflammatory Diseases.

J Inflamm Res 2021 30;14:5023-5050. Epub 2021 Sep 30.

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.

Emerging data indicates that non-coding RNAs (ncRNAs) represent more than just "junk sequences" of the genome and have been found to be involved in multiple diseases by regulating various biological process, including the activation of inflammasomes. As an important aspect of innate immunity, inflammasomes are large immune multiprotein complexes that tightly regulate the production of pro-inflammatory cytokines and mediate pyroptosis; the activation of the inflammasomes is a vital biological process in inflammatory diseases. Recent studies have emphasized the function of ncRNAs in the fine control of inflammasomes activation either by directly targeting components of the inflammasomes or by controlling the activity of various factors that control the activation of inflammasomes; consequently, ncRNAs may represent potential therapeutic targets for inflammatory diseases. Understanding the precise role of ncRNAs in controlling the activation of inflammasomes will help us to design targeted therapies for multiple inflammatory diseases. In this review, we summarize the regulatory role and therapeutic potential of ncRNAs in the activation of inflammasomes by focusing on a range of inflammatory diseases, including microbial infection, sterile inflammatory diseases, and fibrosis-related diseases. Our goal is to provide new ideas and perspectives for future research.
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http://dx.doi.org/10.2147/JIR.S332840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490125PMC
September 2021

Research on Interlayer Bonding Quality Control Method of Dam Concrete Based on Equivalent Age.

Materials (Basel) 2021 Sep 9;14(18). Epub 2021 Sep 9.

School of Mechanics and Civil Engineering, China University of Mining and Technology (Beijing), Beijing 100083, China.

Interlayer bonding quality is the key to the stability and durability of dam concrete. In this study, interlayer splitting tensile strength, relative permeability coefficient, and electric flux of dam concrete at different temperatures were tested. The relationships between equivalent age and strength coefficient, relative permeability coefficient ratio, and electric flux ratio were established. Meanwhile, a comprehensive early-warning and control system of dam interlayer bonding quality based on the above relationships was proposed. The results showed that the interlayer mechanical properties, impermeability, and anti-chloride ion permeability of dam concrete decreased with the increase of temperature. Moreover, the equivalent age was linearly correlated with strength coefficient, relative permeability coefficient ratio, and electric flux ratio of concrete. The correlation coefficients were 0.986, 0.973, and 0.924, respectively. In addition, the interlayer bonding quality of dam concrete can be effectively controlled by the early-warning system established according to the relationship between equivalent age and interlayer properties parameters.
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http://dx.doi.org/10.3390/ma14185192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472006PMC
September 2021

AMPK S-sulfuration contributes to HS donors-induced AMPK phosphorylation and autophagy activation in dopaminergic cells.

Neurochem Int 2021 Nov 14;150:105187. Epub 2021 Sep 14.

Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, 215123, China. Electronic address:

Hydrogen sulfide (HS) serves as a neuromodulator and regulator of neuroinflammation. It is reported to be therapeutic for Parkinson's disease (PD) animal and cellular models. However, whether it affects α-synuclein accumulation in dopaminergic cells, the key pathological feature in PD, is poorly understood. In this study we reported that exogenous HS donors NaHS and GYY4137 (GYY) enhanced the autophagy activity, as indicated by the increases of autophagy marker LC3-II expression and LC3 dots formation even during lysosome inhibition in dopaminergic cell lines and HEK293 cells. The enhancement of HS donors on autophagic flux was mediated by adenosine 5'-monophosphate-activated protein kinase (AMPK)-dependent mammalian target of rapamycin (mTOR) inhibition, as HS donors activated AMPK but reduced the mTOR activity and HS donors-induced LC3-II increase was diminished by mTOR activator. Moreover, point mutation of Cys302 into alanine (C302A) in AMPKα2 subunit abolished the AMPK activation and mTOR inhibition, as well as autophagic flux increase elicited by NaHS. Interestingly, NaHS triggered AMPK S-sulfuration, which was not observed in AMPK C302A-transfected cells. Further, NaHS was able to attenuate α-synuclein accumulation in a cellular model induced by dopamine oxidized metabolite 3, 4-dihydroxyphenylacetaldehyde (DOPAL), and this effect was interfered by autophagy inhibitor wortmannin and also eliminated in AMPK Cys302A-transfected cells. In sum, the findings identified a role of Cys302 S-sulfuration in AMPK activation induced by exogenous HS and demonstrated that HS donors could enhance the autophagic flux via AMPK-mTOR signaling and thus reduce α-synuclein accumulation in vitro.
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http://dx.doi.org/10.1016/j.neuint.2021.105187DOI Listing
November 2021

Association Between Admission Serum Phosphate Level and All-Cause Mortality Among Patients with Spontaneous Intracerebral Hemorrhage.

Risk Manag Healthc Policy 2021 8;14:3739-3746. Epub 2021 Sep 8.

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, People's Republic of China.

Background: Hypophosphatemia was reported to frequently occur in patients with nontraumatic intracranial hemorrhage (ICH); however, the correlation between hypophosphatemia and outcomes of ICH remains unclear. This study aimed to examine the association between admission serum phosphate and all-cause mortality among patients with mild-moderate spontaneous ICH (sICH).

Methods: A total of 851 patients with sICH were enrolled. Serum phosphate was acquired within 24 hours on admission, and participants were divided according to phosphate quartiles. The primary outcome was all-cause mortality within 90 days, and univariate and multivariate models were employed to estimate the mortality risk.

Results: There were significant differences among sICH patients with different phosphate quartiles in terms of age, diastolic blood pressure (DBP), activated partial thromboplastin time (APTT), platelet count, and incidence of respiratory failure events on admission ( < 0.05). Log rank test showed a significant difference in the mortality risk among sICH patients with each phosphate quartile. Univariate Cox regression analysis revealed that age, smoking, DBP, APTT, NIH stroke scale (NIHSS) score, hematoma volume and serum phosphate might be associated with the 90-day all-cause mortality in patients with sICH ( < 0.05). Multivariable Cox regression analysis showed that the crude mortality was 4.3-fold greater in sICH patients with serum phosphate Q1 than those with Q4 ( < 0.001), and remained 3.18-fold higher after adjusting for age, smoking, DBP, APTT, NIHSS score, hematoma volume and early withdrawal of life-sustaining therapy ( = 0.011). Representative operating curve (ROC) analysis showed that admission serum phosphate was predictable for all-cause mortality within 90 days in patients with sICH (area under the ROC = 0.628, < 0.001).

Conclusion: Low admission serum phosphate is strongly associated with a high risk of mortality in patients with mild-moderate sICH, and hypophosphatemia may be a prognostic marker for all-cause mortality in patients with mild-moderate sICH.
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http://dx.doi.org/10.2147/RMHP.S317615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435619PMC
September 2021

Prognostic significance of urinary protein and urinary ketone bodies in acute ischemic stroke.

Nutr Metab Cardiovasc Dis 2021 Jul 26. Epub 2021 Jul 26.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China; Institutes of Neuroscience, Soochow University, Suzhou, 215123, China.

Background And Aims: Prior studies have shown an association between positive urinary protein and an elevated risk of long-term mortality in patients with acute ischemic stroke (AIS); however, data on the short-term prognostic significance of urinary protein and urinary ketone bodies in patients with AIS is sparse.

Methods And Results: A total of 2842 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. Patients were divided into urinary protein positive and negative, urinary ketone bodies positive and negative by urine dipstick. Cox and logistic regression models were used to estimate the effect of urinary protein and urinary ketone bodies on all cause in-hospital mortality and poor outcome upon discharge (modified Rankin Scale score ≥3) in AIS patients. Patients with positive urinary protein was associated with a 2.74-fold and 1.62-fold increase in the risk of in-hospital mortality (adjusted HR 2.74; 95% CI, 1.54-4.89; P-value = 0.001) and poor outcome upon discharge (aOR, 1.62; 95% CI 1.26-2.08; P-value <0.001) in comparison to negative urinary protein after adjusting for potential covariates. Moreover, Patients with positive urinary ketone bodies was associated with 2.11-fold in the risk of poor outcome upon discharge (aOR 2.11; 95% CI 1.52-2.94; P-value <0.001) but not in-hospital mortality (P-value = 0.066) after adjusting for potential covariates.

Conclusions: Urinary protein at admission was independently associated with in-hospital mortality and poor functional outcome at hospital discharge in acute stroke patients and urinary ketone bodies also associated with poor functional outcome at hospital discharge.
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http://dx.doi.org/10.1016/j.numecd.2021.07.010DOI Listing
July 2021

Metabolic potential of microbial community and distribution mechanism of Staphylococcus species during broad bean paste fermentation.

Food Res Int 2021 10 2;148:110533. Epub 2021 Jul 2.

Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China; Synergetic Innovation Center of Jiangsu Modern Industrial Fermentation, Jiangnan University, Wuxi 214122, China. Electronic address:

Although the microbial diversity and structure in bean-based fermented foods have been widely studied, systematic studies on functional microbiota and mechanism of community forms in multi-microbial fermentation systems were still lacking. In this work, the metabolic pathway and functional potential of microbial community in broad bean paste (BBP) were investigated by metagenomics approach, and Staphylococcus, Bacillus, Weissella, Aspergillus and Zygosaccharomyces were found to be the potential predominant populations responsible for substrate alteration and flavor biosynthesis. Among them, Staphylococcus was the most abundant and widespread functional microbe, and closely related Staphylococcus species were diverse and ubiquitously distributed, with the opportunistic pathogen S. gallinarum being the most abundant Staphylococcus specie isolated from BBP. To explain the dominance status of S. gallinarum and species distributions of Staphylococcus genus, we tested the effects of abiotic and biotic factors on three Staphylococcus species using a tractable BBP model, demonstrating that adaptation to environmental conditions (environmental parameters and other functional microbes) led to the dominant position and species coexistence of Staphylococcus, and congeneric competition among Staphylococcus species further shaped ecological distributions of closely related Staphylococcus species. In general, this work revealed the metabolic potential of microbial community and distribution mechanism of Staphylococcus species during BBP fermentation, which could help traditional factories to more precisely control the safety and quality of bean-based fermented foods.
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http://dx.doi.org/10.1016/j.foodres.2021.110533DOI Listing
October 2021

Early-life stress induces prodromal features of Parkinsonian with aging in rats.

J Gerontol A Biol Sci Med Sci 2021 Aug 27. Epub 2021 Aug 27.

Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Early-life stress (ELS) can cause long-term effects on human health, ranging from adolescence to adulthood, and even to gerontic. Although clinical retrospective data suggest that ELS may be related to senile neurodegenerative diseases such as Parkinson's disease (PD), there are few prospective investigations to explore its real contribution to PD. Here, we investigated the behavioral, histochemistical, neuromorphological and transcriptional changes induced by maternal separation (MS), an ELS model. Without neurotoxin, MS rats showed behavioral alterations in olfaction, locomotion and gait characters after depression compared with control rats. Based on neuroimaging and histochemistry, although we found that the dopaminergic system in striatum was impaired after MS, the decrease of striatal dopamine level was ~33%. Consistently, tyrosine hydroxylase immune-staining positive neurons of MS rats in the substantia nigra showed deficit by about 20% in cell counting. Furthermore, using transcriptome sequencing, we discovered many differentially expressed genes (DEGs) of MS rats in striatum significantly enriched in the pathway of dopaminergic synapse, and the biological process of locomotion and neuromuscular process controlling balance. Encouragingly, some representative DEGs relating to PD were singled out. These results suggest that ELS-depression rats potentially mimic some key features of prodromal stage of PD during natural senescence. In conclusion, our findings provide some novel insights into the future pathogenesis and therapeutic studies for PD related to depression.
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http://dx.doi.org/10.1093/gerona/glab253DOI Listing
August 2021

Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery.

Front Pharmacol 2021 14;12:713963. Epub 2021 Jul 14.

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Neurodegenerative disease (NDD), including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by the progressive loss of neurons which leads to the decline of motor and/or cognitive function. Currently, the prevalence of NDD is rapidly increasing in the aging population. However, valid drugs or treatment for NDD are still lacking. The clinical heterogeneity and complex pathogenesis of NDD pose a great challenge for the development of disease-modifying therapies. Numerous animal models have been generated to mimic the pathological conditions of these diseases for drug discovery. Among them, zebrafish () models are progressively emerging and becoming a powerful tool for in vivo study of NDD. Extensive use of zebrafish in pharmacology research or drug screening is due to the high conserved evolution and 87% homology to humans. In this review, we summarize the zebrafish models used in NDD studies, and highlight the recent findings on pharmacological targets for NDD treatment. As high-throughput platforms in zebrafish research have rapidly developed in recent years, we also discuss the application prospects of these new technologies in future NDD research.
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http://dx.doi.org/10.3389/fphar.2021.713963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317260PMC
July 2021

Free thyroxine, brain frailty and clock drawing test performance in patients with acute minor stroke or transient ischaemic attack.

Clin Endocrinol (Oxf) 2021 Jul 26. Epub 2021 Jul 26.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Objective: Thyroid dysfunction is associated with an elevated risk of cognitive decline, but the mechanism underlying this relationship is elusive. In this study, we investigate the relationships between free thyroxine (FT4), brain frailty and clock drawing test (CDT) performance in patients with acute minor stroke or transient ischaemic attack (TIA).

Design, Patients And Measurements: A total of 204 consecutive patients admitted to our hospital within 72 h after the onset of acute minor stroke or TIA were prospectively enroled and categorized in terms of quartiles of FT4 between March 2018 and August 2019. Brain frailty on magnetic resonance imaging was rated according to previously published criteria. Cognitive performance was assessed with the CDT.

Results: Generalized linear analysis revealed that FT4 was independently associated with higher brain frailty score after adjusting potential confounders (β, 0.03; 95% confidence interval [CI], 0.00-0.06; p = 0.0205), which is consistent with the result of FT4 (quartile) as a categorical variable (β, 0.34; 95% CI, 0.01-0.68; p = 0.0059; p  = 0.0807). A nonlinear relationship was detected between FT4 and brain frailty score, which had an inflection point of 1.19. FT4 was also associated with poor CDT performance (odds ratio, 1.15; 95% CI, 1.04-1.26; p = 0.0051). And mediation analysis found that brain frailty partially mediated the positive relationship between FT4 and poor CDT performance (indirect effect = 0.0024; 95% CI, 0.0003-0.01, p = 0.04).

Conclusions: Our findings suggested that a higher FT4 level was associated with a higher brain frailty score and poorer CDT performance, and brain frailty might play an important effect on the association between FT4 and cognitive decline.
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http://dx.doi.org/10.1111/cen.14564DOI Listing
July 2021

Cognition and transcranial sonography in Parkinson's disease patients with or without orthostatic hypotension.

Brain Behav 2021 08 21;11(8):e2252. Epub 2021 Jul 21.

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Background: Orthostatic hypotension (OH) is a common nonmotor symptom in patients with Parkinson's disease (PD), with an incidence ranging from 14% to 54%.

Aims: This study explored changes in cognition and transcranial sonography (TCS) findings in patients with PD and OH.

Methods: We enrolled PD patients who visited the outpatient or inpatient department from 2017 to 2020. Blood pressure was measured in different positions, and demographic data were collected. Motor and nonmotor symptoms were evaluated using standard scales. A subset of 107 patients underwent TCS.

Results: We enrolled 66 PD-OH patients and 92 PD-no orthostatic hypotension (NOH) patients. There were no significant differences in gender, age, disease duration, or Hoehn and Yahr stage between groups. Binary logistic regression revealed age as an independent risk factor for OH in PD patients. There were statistically significant group differences in visuospatial and executive function and Unified Parkinson's Disease Rating Scale (UPDRS) I and II scores (p < .05). Among PD-OH patients, there was a statistically significant difference in UPDRS II and III scores between patients with or without clinical symptoms (p < .05). The substantia nigra (SN) area was significantly larger in PD-NOH patients (0.45 ± 0.18 cm ) than PD-OH patients (0.34 ± 0.16 cm ) (p < .05).

Conclusions: PD-OH patients had poorer visuospatial and executive function and lower UPDRS I and II scores compared with PD-NOH patients. Within the PD-OH group, there was no significant difference in cognition between patients with or without clinical symptoms. The difference in the SN area may indicate different subtypes of PD or a tendency to develop parkinsonism syndrome.
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http://dx.doi.org/10.1002/brb3.2252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413744PMC
August 2021

Association between homocysteine and third ventricle dilatation, mesencephalic area atrophy in Parkinson's disease with cognitive impairment.

J Clin Neurosci 2021 Aug 21;90:273-278. Epub 2021 Jun 21.

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.

Objectives: This study aimed to explore the association of homocysteine (Hcy) with third ventricle (V3) dilatation and mesencephalic area (MA) atrophy as determined by transcranial sonography (TCS) in Parkinson's disease (PD) with cognitive impairment.

Methods: The final statistical analysis included 101 PD patients and 20 age- and sex-matched controls. Using the Movement Disorder Society (MDS) level II criteria for PD with cognitive impairment, we categorized the PD patients into PD with normal cognition group (PD) and PD with cognitive impairment group (PDC). All subjects underwent TCS and laboratory analysis.

Results: The V3 width (r = 0.349, P = 0.005) and the MA (r = -0.484, P < 0.001) were significantly correlated with the Hcy concentration in the PDC patients. Binary logistic regression analysis revealed that age (OR [95% CI] = 1.114 [0.991-1.251], P = 0.002), and Hcy level (OR [95% CI] = 0.931 [0.752-1.153], P = 0.411) were independent risk factors for V3 dilatation. Hcy level (OR [95% CI] = 0.557 [0.323-0.967], P = 0.035) were independent risk factors for MA atrophy. After adjustment for confounding factors, the odds ratio of V3 dilatation was 3.50 (95% CI 1.054-11.399, P = 0.031) and the odds ratio of MA atrophy was 4.67 (95% CI 1.395-15.602, P = 0.012) in the patients with higher Hcy level compared with the lower level.

Conclusions: The results revealed a close association between the V3 width, MA and Hcy concentration in PD patients with cognitive impairment. We hypothesized that increased Hcy concentration played a significant role in the development of brain atrophy in PD with cognitive impairment.
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http://dx.doi.org/10.1016/j.jocn.2021.06.006DOI Listing
August 2021

Chemical Autophagy Regulators.

Adv Exp Med Biol 2021 ;1208:289-309

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Autophagy is a catabolic process that removes aggregated proteins and damaged organelles via lysosomal degradation. Increasing evidence suggests that dysfunction of autophagy is associated with a variety of human pathologies, including aging, cancer, neurodegenerative diseases, heart diseases, diabetes, and other metabolic diseases. Current research suggests that the regulation of autophagy may be a novel target for the treatment of these diseases. For this purpose, it is essential to have a deep understanding on the molecular details of autophagy and its regulatory network in each of the disease contexts. Over the years, a variety of chemical autophagy inducers and inhibitors has been developed. The application of these autophagy regulators can assist us in the exploration of the mechanism and therapeutic potential of autophagy regulation. In this chapter, we summarize the recent advances in chemical autophagy regulators to provide methodological support for autophagy research.
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http://dx.doi.org/10.1007/978-981-16-2830-6_13DOI Listing
July 2021

Prediction Model of Concrete Initial Setting Time Based on Stepwise Regression Analysis.

Materials (Basel) 2021 Jun 10;14(12). Epub 2021 Jun 10.

State Key Laboratory of Hydroscience and Engineering, Tsinghua University, Beijing 100084, China.

Mass concrete is usually poured in layers. To ensure the interlayer bonding quality of concrete, the lower layer should be kept in a plastic state before the upper layer is added. Ultimately, it will lead to the prediction of concrete setting time as a critical task in concrete pouring. In this experiment, the setting time of concrete in laboratory and field environments was investigated. The equivalent age of concrete at the initial setting was also analyzed based on the maturity theory. Meanwhile, factors affecting the setting time in the field environment were studied by means of multiple stepwise regression analysis. Besides, the interlayer splitting tensile strength of concrete subjected to different temperatures and wind speeds was determined. The results of laboratory tests show that both setting time and interlayer splitting tensile strength of concrete decrease significantly with the increase of air temperature and wind speed. In addition, the equivalent age of concrete at initial setting remains the same when subjected to different temperatures, while it decreases obviously with the increase of wind speed. In the field environment, the equivalent age of concrete at initial setting is greatly different, which is related to the variability of relative humidity and wind speed. The average air temperature and maximum wind speed are the main factors affecting the initial setting time of concrete. Furthermore, a prediction model is established based on the stepwise regression analysis results, which can predict the actual setting state in real-time, and hence controlling the interlayer bonding quality of dam concrete.
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http://dx.doi.org/10.3390/ma14123201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229610PMC
June 2021

Effect of Sleep-Disordered Breathing During Rapid Eye Movement Sleep and Non-Rapid Eye Movement sleep on Acute Ischemic Stroke.

J Stroke Cerebrovasc Dis 2021 Aug 12;30(8):105913. Epub 2021 Jun 12.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Department of Neurology, Taicang Affiliated Hospital of Soochow University, The first People's Hospital of Taicang, Taicang 215400, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China. Electronic address:

Objectives: Sleep-disordered breathing adversely impacts stroke outcomes. We investigated whether sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep differentially influenced stroke outcomes.

Materials And Methods: Acute ischemic stroke patients who finished polysomnography within 14 days of stroke onset from April 2010 to August 2018 were reviewed. Patients were divided into four groups according to apnea-hypopnea index during rapid eye movement sleep and non-rapid eye movement sleep. The modified Rankin Scale was used to evaluate short-term outcome. During January and April 2019, another follow-up was performed for long-term outcomes, including stroke-specific quality-of-life scale, modified Rankin Scale, stroke recurrence and death.

Results: Of 140 patients reviewed, 109 were finally recruited. Although patients with sleep-disordered breathing during non-rapid eye movement sleep only and with sleep-disordered breathing during both rapid eye movement sleep and non-rapid eye movement sleep had higher apnea-hypopnea indices and more disrupted sleep structures, short-term and long-term outcomes did not significantly different between four groups. In Logistic regression analysis, apnea-hypopnea index (p = 0.013, OR 1.023, 95%CI 1.005-1.042) was found independently associated with short-term outcome. Rapid eye movement sleep latency (p = 0.045, OR 0.994, 95%CI 0.987-1.000) was found independently associated with quality of life. Apnea-hypopnea indices during rapid eye movement sleep or non-rapid eye movement sleep were not significantly associated with short-term or long-term outcomes.

Conclusions: Apnea-hypopnea index is an independent risk factor of short-term outcome of acute ischemic stroke while sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep do not affect stroke outcomes differently.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105913DOI Listing
August 2021

Long Noncoding RNA: Regulatory Mechanisms and Therapeutic Potential in Sepsis.

Front Cell Infect Microbiol 2021 12;11:563126. Epub 2021 May 12.

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is characterized by a hyperinflammatory state accompanied by immunosuppression. Long noncoding RNAs (lncRNAs) are noncoding RNAs longer than 200 nucleotides and have important roles in mediating various biological processes. Recently, lncRNAs were found to exert both promotive and inhibitory immune functions in sepsis, thus participating in sepsis regulation. Additionally, several studies have revealed that lncRNAs are involved in sepsis-induced organ dysfunctions, including cardiovascular dysfunction, acute lung injury, and acute kidney injury. Considering the lack of effective biomarkers for early identification and specific treatment for sepsis, lncRNAs may be promising biomarkers and even targets for sepsis therapies. This review systematically highlights the recent advances regarding the roles of lncRNAs in sepsis and sheds light on their use as potential biomarkers and treatment targets for sepsis.
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http://dx.doi.org/10.3389/fcimb.2021.563126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149942PMC
June 2021

Mutant-TMEM230-induced neurodegeneration and impaired axonal mitochondrial transport.

Hum Mol Genet 2021 Jul;30(16):1535-1542

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Parkinson's disease (PD) is a neurodegenerative disease with movement disorders including resting tremor, rigidity, bradykinesia and postural instability. Recent studies have identified a new PD associated gene, TMEM230 (transmembrane protein 230). However, the pathological roles of TMEM230 and its variants are not fully understood. TMEM230 gene encodes two protein isoforms. Isoform2 is the major protein form (~95%) in human. In this study, we overexpress isoform2 TMEM230 variants (WT or PD-linked *184Wext*5 mutant) or knockdown endogenous protein in cultured SH-5Y5Y cells and mouse primary hippocampus neurons to study their pathological roles. We found that overexpression of WT and mutant TMEM230 or knockdown of endogenous TMEM230-induced neurodegeneration and impaired mitochondria transport at the retrograde direction in axons. Mutant TMEM230 caused more severe neurotoxicity and mitochondrial transport impairment than WT-TMEM230 did. Our results demonstrate that maintaining TMEM230 protein levels is critical for neuron survival and axon transport. These findings suggest that mutant-TMEM230-induced mitochondrial transport impairment could be the early event leading to neurite injury and neurodegeneration in PD development.
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http://dx.doi.org/10.1093/hmg/ddab128DOI Listing
July 2021

Prevalence and profile of nocturnal disturbances in Chinese patients with advanced-stage Parkinson's disease: a cross-sectional epidemiology study.

BMC Neurol 2021 May 12;21(1):194. Epub 2021 May 12.

Department of Neurology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: The impact of nocturnal disturbance (ND) in Parkinson's disease on quality of life of patients in Western Countries is increasingly understood. Our study aimed to investigate ND prevalence and its quality of life impact in patients with advanced Parkinson's disease in China.

Methods: In a multicenter, tertiary-care hospital, outpatient-based, cross-sectional study, patients with advanced Parkinson's disease (Modified Hoehn & Yahr [H&Y] Stage II-IV with ≥3 h awake "off" time/day) from 10 tertiary hospitals throughout China completed the Parkinson's Disease Sleep Scale-2 (PDSS-2) and Parkinson's Disease Questionnaire-39 (PDQ-39). The primary endpoint was the percentage of patients with significant ND (PDSS-2 total score ≥ 15). Additional endpoints were demographic and clinical characteristics, PDSS-2 and PDQ-39 total and subscale scores, correlation between PDSS-2 and PDQ-39, and risk factors for ND and higher PDSS-2 or PDQ-39 scores.

Results: Of 448 patients analyzed (mean age 63.5 years, 47.3% female), 70.92% (95% confidence interval: 66.71, 75.13) had significant ND. Presence of ND and higher PDSS-2 scores were associated with longer disease duration and higher H&Y stage. Presence of ND was also associated with more awake "off" time/day and female sex. PDQ-39 scores were significantly worse for patients with ND versus those without ND; worse scores were associated with more awake "off" time/day, female sex, and higher H&Y stage. PDSS-2 and PDQ-39 total scores were associated: Pearson correlation coefficient 0.62 (p < 0.001).

Conclusions: In China, ND was highly prevalent in patients with advanced Parkinson's disease and adversely impacted quality of life. This study highlights the importance of early diagnosis and optimized management of ND in patients with Parkinson's disease in China.
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http://dx.doi.org/10.1186/s12883-021-02217-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114718PMC
May 2021

Microglial MT1 activation inhibits LPS-induced neuroinflammation via regulation of metabolic reprogramming.

Aging Cell 2021 06 8;20(6):e13375. Epub 2021 May 8.

Department of Neurology, Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Although its pathogenesis remains unclear, a number of studies indicate that microglia-mediated neuroinflammation makes a great contribution to the pathogenesis of PD. Melatonin receptor 1 (MT1) is widely expressed in glia cells and neurons in substantia nigra (SN). Neuronal MT1 is a neuroprotective factor, but it remains largely unknown whether dysfunction of microglial MT1 is involved in the PD pathogenesis. Here, we found that MT1 was reduced in microglia of SN in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Microglial MT1 activation dramatically inhibited lipopolysaccharide (LPS)-induced neuroinflammation, whereas loss of microglial MT1 aggravated it. Metabolic reprogramming of microglia was found to contribute to the anti-inflammatory effects of MT1 activation. LPS-induced excessive aerobic glycolysis and impaired oxidative phosphorylation (OXPHOS) could be reversed by microglial MT1 activation. MT1 positively regulated pyruvate dehydrogenase alpha 1 (PDHA1) expression to enhance OXPHOS and suppress aerobic glycolysis. Furthermore, in LPS-treated microglia, MT1 activation decreased the toxicity of conditioned media to the dopaminergic (DA) cell line MES23.5. Most importantly, the anti-inflammatory effects of MT1 activation were observed in LPS-stimulated mouse model. In general, our study demonstrates that MT1 activation inhibits LPS-induced microglial activation through regulating its metabolic reprogramming, which provides a mechanistic insight for microglial MT1 in anti-inflammation.
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http://dx.doi.org/10.1111/acel.13375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208780PMC
June 2021

Restless legs syndrome and perceived olfactory and taste dysfunction: A community-based study.

Eur J Neurol 2021 08 24;28(8):2688-2693. Epub 2021 May 24.

Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.

Background And Purpose: Restless legs syndrome (RLS) has been suggested as a prodromal symptom of Parkinson disease (PD). Olfactory or taste dysfunction can also occur preceding PD diagnosis. However, whether RLS is associated with chemosensory dysfunction remains unknown. We thus aim to investigate the association between RLS and perceived olfactory and taste dysfunction.

Methods: We performed a cross-sectional analysis including 90,337 Chinese adults free of neurodegenerative diseases in the Kailuan study in 2016. Presence of RLS was defined using revised RLS diagnostic criteria or the Cambridge-Hopkins questionnaire for RLS. Perceived olfactory and taste dysfunction was collected via a questionnaire. The association between RLS and perceived olfactory and taste dysfunction was assessed using logistic regression model, adjusting for potential cofounders such as age, sex, and medical history.

Results: RLS was associated with high odds of having perceived olfactory and/or taste dysfunction (adjusted odds ratio = 5.92, 95% confidence interval = 3.11-11.3). The significant association persisted when using the Cambridge-Hopkins questionnaire (adjusted odds ratio = 5.55, 95% confidence interval = 2.37-13.0) or when excluding participants with major chronic diseases.

Conclusions: RLS was associated with increased odds of perceived olfactory and taste dysfunction.
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http://dx.doi.org/10.1111/ene.14890DOI Listing
August 2021

Sex and onset-age-related features of excessive daytime sleepiness and night-time sleep in patients with Parkinson's disease.

BMC Neurol 2021 Apr 19;21(1):165. Epub 2021 Apr 19.

Department of Neurology and Suzhou Clinical Research Center of Neurological Diseases, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu Province, China.

Background: The clinical characteristics of Parkinson's disease (PD) differ between men and women, and late- and early-onset patients, including motor symptoms and some nonmotor symptoms, such as cognition, anxiety, and depression.

Objective: To explore the features of excessive daytime sleepiness (EDS) and night-time sleep quality in PD patients of different sexes and age at onset (AAO).

Methods: Demographic data and clinical characteristics of 586 PD patients were collected. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the daytime drowsiness and nocturnal sleep. Multivariate logistic regression analysis was used to explore the risk factors of EDS and poor night-time sleep quality.

Results: Sleep disorders were common in PD patients. EDS was more prominent in men than in women. There was no significant difference in ESS scores between late-onset PD (LOPD) and early-onset PD. LOPD patients had a higher probability of poor night-time sleep quality. Male sex, disease duration, and depression were risk factors for EDS. In all patients of both sexes and all AAO, depression was a risk factor for poor night-time sleep.

Conclusion: More attention should be paid to sleep disorders of PD patients, especially male LOPD patients. Depression is a common risk factor for EDS and poor sleep quality in PD patients.
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http://dx.doi.org/10.1186/s12883-021-02192-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054359PMC
April 2021

Development of a defined autochthonous starter through dissecting the seasonal microbiome of broad bean paste.

Food Chem 2021 Mar 20;357:129625. Epub 2021 Mar 20.

Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China; Synergetic Innovation Center of Jiangsu Modern Industrial Fermentation, Jiangnan University, Wuxi 214122, China. Electronic address:

Bean-based fermentation foods are usually ripened in open environment, which would lead to inconsistencies in flavor and quality between batches. The physicochemical metabolism and microbial community of seasonal broad bean paste (BBP) were compared to distinguish discriminant metabolites and unique taxa, as well as their specific reasons for different flavor and quality in this study. Here, we found that environmental variables led to the seasonal distribution of microbiota, and differential microorganisms further contributed to the inconsistency of flavor quality, in which Lactobacillales was responsible for the higher titratable acid and amino acid nitrogen concentration in winter pei, while Saccharomycetales benefited the formation of volatile flavor substances in autumn pei. Additionally, we compared the effect of different combinations of Lactobacillales with Zygosaccharomyces rouxii on the quality of BBP, and found that W. confusa was more suitable for BBP fermentation rather than T. halophilus in terms of sensory characteristics and physicochemical metabolites.
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http://dx.doi.org/10.1016/j.foodchem.2021.129625DOI Listing
March 2021

Comparative transcriptome analysis of transcripts of uncertain coding potential in septic myocardial depression.

BMC Cardiovasc Disord 2021 04 8;21(1):166. Epub 2021 Apr 8.

Department of Pediatrics, PICU, Shengjing Hospital of China Medical University, No. 36, SanHao Street, Shenyang City, 110004, Liaoning Province, People's Republic of China.

Background: Septic shock with myocardial depression is very common in intensive care units. However, the exact molecular mechanisms underlying sepsis-induced myocardial depression remain unclear. Whether the profiles of transcripts of uncertain coding potential (TUCPs) differ between patients with and without myocardial depression is also unknown. Our study aimed to find expression differences between groups of TUCPs and determine their potential functions in a preclinical model.

Methods: We generated rat models of hypodynamic septic shock induced by lipopolysaccharide. A total of 12 rats were established and left ventricular tissue from each was collected. We performed RNA-seq to identify TUCPs in each sample. Transcripts with an corrected P value of < 0.05 were defined as differentially expressed (DE). We also performed GO terms and KEGG analysis to identify the potential functions of DE TUCPs.

Results: A total of 4,851 TUCPs were identified in heart samples, 85 of which were expressed differently between the sepsis and control groups. Further bioinformatic analyses suggested that TUCPs play important roles in myocardial contraction, energy regulation, and metabolic processes, and are also involved in the regulation of several pathways.

Conclusion: Our results demonstrate that TUCPs both participate in and mediate the pathological process of myocardial depression. Our study improves the understanding of the basic molecular mechanisms underlying myocardial depression from a novel perspective.
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http://dx.doi.org/10.1186/s12872-021-01973-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028820PMC
April 2021

Remnant Cholesterol and Common Carotid Artery Intima-Media Thickness in Patients With Ischemic Stroke.

Circ Cardiovasc Imaging 2021 04 9;14(4):e010953. Epub 2021 Apr 9.

Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China (S.Q., T.X., C.Z.).

Background: Remnant cholesterol makes great contribution to residual risk of cardiovascular disease, but population-based evidence on the relationship between remnant cholesterol and atherosclerosis is rare. Common carotid artery intima-media thickness (cIMT) is an imaging marker of subclinical atherosclerosis. We aimed to explore the association between remnant cholesterol levels and cIMT in patients with ischemic stroke.

Methods: One thousand four hundred ninety-six ischemic stroke patients with baseline serum lipids and carotid artery imaging data were included in this analysis. Fasting remnant cholesterol was calculated as total cholesterol minus HDL (high-density lipoprotein) cholesterol minus LDL (low-density lipoprotein) cholesterol. Abnormal cIMT was defined as mean cIMT and maximum cIMT value ≥1 mm. Logistic regression and restricted cubic spline models were used to assess the relationships between remnant cholesterol levels and abnormal cIMT.

Results: The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 2.06 (1.46-2.91) for abnormal mean cIMT and 1.70 (1.23-2.35) for abnormal maximum cIMT. There were linear associations between remnant cholesterol levels and both abnormal mean cIMT ( for linearity, <0.001) and abnormal maximum cIMT ( for linearity, 0.003). Moreover, the remnant cholesterol-cIMT association remained significant in the subsample of patients with optimal LDL cholesterol levels (n=179).

Conclusions: Elevated fasting remnant cholesterol levels were positively associated with mean cIMT and maximum cIMT in patients with ischemic stroke, even in patients with optimal LDL cholesterol levels. Future prospective studies are needed to verify our findings and to assess the effect of remnant cholesterol-lowering interventions in patients with ischemic stroke.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.010953DOI Listing
April 2021

Environmental Risk Factors and Congenital Heart Disease: An Umbrella Review of 165 Systematic Reviews and Meta-Analyses With More Than 120 Million Participants.

Front Cardiovasc Med 2021 11;8:640729. Epub 2021 Mar 11.

Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.

The etiology of congenital heart disease (CHD) has been extensively studied in the past decades. Therefore, it is critical to clarify clear hierarchies of evidence between types of environmental factors and CHD. Electronic searches in PubMed, Embase, Web of Science, Cochrane database were conducted from inception to April 20, 2020 for meta-analyses investigating the aforementioned topic. Overall, 41 studies including a total of 165 meta-analyses of different environmental factors and CHD were examined, covering a wide range of risk factors. The summary random effects estimates were significant at < 0.05 in 63 meta-analyses (38%), and 15 associations (9%) were significant at < 10. Of these meta-analyses, eventually one risk factor (severe obesity; relative risk: 1.38, 95% confidence interval: 1.30-1.47) had significant summary associations at < 10, included more than 1,000 cases, had 95% prediction intervals excluding the null value, and were not suggestive of large heterogeneity ( < 50%), small-study effects (-value for Egger's test > 0.10), or excess significance ( > 0.10). Eight associations (5%) (including maternal lithium exposure, maternal obesity, maternal alcohol consumption, and maternal fever) had results that were significant at < 10, included more than 1,000 cases, and had 95% prediction intervals excluding the null value (highly suggestive). This umbrella review shows that many environmental factors have substantial evidence in relation to the risk of developing CHD. More and better-designed studies are needed to establish robust evidence between environmental factors and CHD. [PROSPERO], identifier [CRD42020193381].
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http://dx.doi.org/10.3389/fcvm.2021.640729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006458PMC
March 2021

Intranasal Transplantation of Human Neural Stem Cells Ameliorates Alzheimer's Disease-Like Pathology in a Mouse Model.

Front Aging Neurosci 2021 10;13:650103. Epub 2021 Mar 10.

Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou, China.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairments, which has no effective therapy. Stem cell transplantation shows great potential in the therapy of various disease. However, the application of stem cell therapy in neurological disorders, especially the ones with a long-term disease course such as AD, is limited by the delivery approach due to the presence of the brain blood barrier. So far, the most commonly used delivery approach in the therapy of neurological disorders with stem cells in preclinical and clinical studies are intracranial injection and intrathecal injection, both of which are invasive. In the present study, we use repetitive intranasal delivery of human neural stem cells (hNSCs) to the brains of APP/PS1 transgenic mice to investigate the effect of hNSCs on the pathology of AD. The results indicate that the intranasally transplanted hNSCs survive and exhibit extensive migration and higher neuronal differentiation, with a relatively limited glial differentiation. A proportion of intranasally transplanted hNSCs differentiate to cholinergic neurons, which rescue cholinergic dysfunction in APP/PS1 mice. In addition, intranasal transplantation of hNSCs attenuates β-amyloid accumulation by upregulating the expression of β-amyloid degrading enzymes, insulin-degrading enzymes, and neprilysin. Moreover, intranasal transplantation of hNSCs ameliorates other AD-like pathology including neuroinflammation, cholinergic dysfunction, and pericytic and synaptic loss, while enhancing adult hippocampal neurogenesis, eventually rescuing the cognitive deficits of APP/PS1 transgenic mice. Thus, our findings highlight that intranasal transplantation of hNSCs benefits cognition through multiple mechanisms, and exhibit the great potential of intranasal administration of stem cells as a non-invasive therapeutic strategy for AD.
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http://dx.doi.org/10.3389/fnagi.2021.650103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987677PMC
March 2021

Efficacy and Safety of Pramipexole Sustained Release versus Immediate Release Formulation for Nocturnal Symptoms in Chinese Patients with Advanced Parkinson's Disease: A Pilot Study.

Parkinsons Dis 2021 3;2021:8834950. Epub 2021 Mar 3.

Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: To explore the efficacy and safety of pramipexole sustained release (SR) versus pramipexole immediate release (IR) in treating nocturnal symptoms in levodopa-treated Chinese patients with advanced Parkinson's disease (PD) and sleep disturbances.

Method: SUSTAIN was an open-label, randomised, active-controlled parallel group exploratory pilot study (NCT03521635). A total of 98 patients were randomly allocated (1 : 1) to either pramipexole SR ( = 49) or pramipexole IR ( = 49) groups. The primary endpoint was a change from baseline in PD Sleep Scale 2 version (PDSS-2) total score at 18 weeks. A reduction in score represents improvement. Secondary endpoints included Nocturnal Hypokinesia Questionnaire, Scales for Outcomes in PD Sleep Scale, Early Morning Off (EMO), Epworth Sleepiness Scale, PD Questionnaire-8, and responder rates as measured by PDSS-2 total score (<18), EMO scores (≥1 point change), Clinical Global Impression Improvement scale, and Patient Global Impression-Improvement scale. Other endpoints included motor complications (MDS-UPDRS part IV) score. Adverse events were evaluated for each group.

Results: The mean pramipexole dose for both groups was 1.5 mg/day at week 18, and the mean changes in PDSS-2 total score for pramipexole SR and IR were -13.7 (95% CI -16.0 to -11.4) and -14.4 (-16.8 to -12.0) (difference of 0.7; =0.688). Change from baseline for both groups achieved the minimal clinical important difference threshold (MCID = -3.44). No significant difference was observed in change from baseline for other measures of sleep-related disturbances or responder rates. For motor complications, a greater improvement in MDS-UPDRS part IV score was observed in pramipexole SR over IR (-3.4 vs -2.3; treatment group difference: -1.1; =0.036). Both groups had comparable safety profiles.

Conclusion: In Chinese patients with advanced PD and sleep disturbances, pramipexole SR and IR have similar benefits in the treatment of nocturnal symptoms and safety, and an improvement from baseline in nocturnal symptoms was observed regardless of pramipexole formulation.
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http://dx.doi.org/10.1155/2021/8834950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946461PMC
March 2021

Advances in intranasal application of stem cells in the treatment of central nervous system diseases.

Stem Cell Res Ther 2021 03 24;12(1):210. Epub 2021 Mar 24.

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.

Stem cells are characterized by their self-renewal and multipotency and have great potential in the therapy of various disorders. However, the blood-brain barrier (BBB) limits the application of stem cells in the therapy of neurological disorders, especially in a noninvasive way. It has been shown that small molecular substances, macromolecular proteins, and even stem cells can bypass the BBB and reach the brain parenchyma following intranasal administration. Here, we review the possible brain-entry routes of transnasal treatment, the cell types, and diseases involved in intranasal stem cell therapy, and discuss its advantages and disadvantages in the treatment of central nervous system diseases, to provide a reference for the application of intranasal stem cell therapy.
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http://dx.doi.org/10.1186/s13287-021-02274-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992869PMC
March 2021

Dynamic change of heart rate in the acute phase and clinical outcomes after intracerebral hemorrhage: a cohort study.

J Intensive Care 2021 Mar 18;9(1):28. Epub 2021 Mar 18.

Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, 215123, Jiangsu, China.

Background: Dynamic change of heart rate in the acute phase and clinical outcomes after intracerebral hemorrhage (ICH) remains unknown. We aimed to investigate the associations of heart rate trajectories and variability with functional outcome and mortality in patients with acute ICH.

Methods: This prospective study was conducted among 332 patients with acute ICH. Latent mixture modeling was used to identify heart rate trajectories during the first 72 h of hospitalization after ICH onset. Mean and coefficient of variation of heart rate measurements were calculated. The study outcomes included unfavorable functional outcome, ordinal shift of modified Rankin Scale score, and all-cause mortality.

Results: We identified 3 distinct heart rate trajectory patterns (persistent-high, moderate-stable, and low-stable). During 3-month follow-up, 103 (31.0%) patients had unfavorable functional outcome and 46 (13.9%) patients died. In multivariable-adjusted model, compared with patients in low-stable trajectory, patients in persistent-high trajectory had the highest odds of poor functional outcome (odds ratio 15.06, 95% CI 3.67-61.78). Higher mean and coefficient of variation of heart rate were also associated with increased risk of unfavorable functional outcome (P trend < 0.05), and the corresponding odds ratios (95% CI) comparing two extreme tertiles were 4.69 (2.04-10.75) and 2.43 (1.09-5.39), respectively. Likewise, similar prognostic effects of heart rate dynamic changes on high modified Rankin Scale score and all-cause mortality were observed.

Conclusions: Persistently high heart rate and higher variability in the acute phase were associated with increased risk of unfavorable functional outcome in patients with acute ICH.
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http://dx.doi.org/10.1186/s40560-021-00540-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971394PMC
March 2021

Depression Induced by Chronic Unpredictable Mild Stress Increases Susceptibility to Parkinson's Disease in Mice via Neuroinflammation Mediated by P2X7 Receptor.

ACS Chem Neurosci 2021 04 18;12(7):1262-1272. Epub 2021 Mar 18.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

The relationship between depression and Parkinson's disease (PD) is complicated and still not fully understood. We investigated whether depression increased the susceptibility to PD and whether this resulted from neuroinflammation mediated by purinergic ligand-gated ion channel 7 receptor (P2X7R) of microglia in mice. Depression was induced by a 14-day chronic unpredictable mild stress (CUMS), and PD was induced by 1-day acute injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Before MPTP administration, some mice were given brilliant blue G (BBG), a P2X7R inhibitor. Changes in depression and motor function were assessed by sucrose preference, tail suspension, open field, and rotating rod tests. Differences in P2X7R, caspase-1, NLRP3 inflammasome, interleukin (IL)-1β, tyrosine hydroxylase (TH), and microglial activation among experimental groups were detected by immunofluorescence, immunohistochemistry, western blotting, and ELISA. CUMS-induced depression-like behavior, and MPTP induced PD in mice. CUMS mice had no motor dysfunction, but the dyskinesia and loss of TH-positive neurons in the substantia nigra after MPTP treatment were more serious than with MPTP treatment alone. With behavioral changes, neuroinflammatory markers, such as caspase-1, NLRP3 and IL-1β increased, and microglia were activated as well as expression of P2X7R increased. Additionally, BBG partly reversed the above abnormalities. Summarily, we suggest that CUMS aggravates dyskinesia and death of dopaminergic neurons in an MPTP-PD model via promoting activation of microglia and neuroinflammation, which may be mediated by P2X7R. Inhibition of P2X7R could be a new control strategy for PD associated with depression.
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http://dx.doi.org/10.1021/acschemneuro.1c00095DOI Listing
April 2021

Fatigue correlates with sleep disturbances in Parkinson disease.

Chin Med J (Engl) 2020 Dec 16;134(6):668-674. Epub 2020 Dec 16.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.

Background: Many Parkinson disease (PD) patients complain about chronic fatigue and sleep disturbances during the night. The objective of this study is to determine the relationship between fatigue and sleep disturbances by using polysomnography (PSG) in PD patients.

Methods: Two hundred and thirty-two PD patients (152 with mild fatigue and 80 with severe fatigue) were recruited in this study. Demographic information and clinical symptoms were collected. Fatigue severity scale (FSS) was applied to evaluate the severity of fatigue, and PSG was conducted in all PD patients. FSS ≥4 was defined as severe fatigue, and FSS <4 was defined as mild fatigue. Multivariate logistic regression and linear regression models were used to investigate the associations between fatigue and sleep disturbances.

Results: Patients with severe fatigue tended to have a longer duration of disease, higher Unified Parkinson Disease Rating Scale score, more advanced Hoehn and Yahr stage, higher daily levodopa equivalent dose, worse depression, anxiety, and higher daytime sleepiness score. In addition, they had lower percentage of rapid eye movement (REM) sleep (P = 0.009) and were more likely to have REM sleep behavior disorder (RBD) (P = 0.018). Multivariate logistic regression analyses found that the presence of RBD and proportion of REM sleep were the independent predictors for fatigue. After the adjustment of age, sex, duration, body mass index, severity of disease, scores of Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and other sleep disorders, proportion of REM sleep and degree of REM sleep without atonia in patients with PD were still associated with FSS score.

Conclusion: Considering the association between fatigue, RBD, and the altered sleep architecture, fatigue is a special subtype in PD and more studies should be focused on this debilitating symptom.
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http://dx.doi.org/10.1097/CM9.0000000000001303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990014PMC
December 2020
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