1.Exercise-induced Modulation of Ferroptosis: Potential Mechanisms for Improvement in Parkinson’s Disease
Dong-Lei LU ; Wen-Yu ZHANG ; Si-Jie TAN ; Feng-Ying YANG
Progress in Biochemistry and Biophysics 2024;51(11):2880-2896
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by muscle rigidity, resting tremor, and postural instability, which severely impair the quality of life in middle-aged and elderly individuals. PD’s pathogenesis is complex, involving oxidative stress, immune inflammation, and genetic factors. Despite extensive research, precise therapeutic targets for PD remain elusive, necessitating further investigation into its underlying mechanisms. Recent studies highlight the pivotal role of regional brain iron overload, oxidative stress, and lipid peroxidation in PD’s pathogenesis. Ferroptosis, a form of regulated cell death driven by iron dependency and lipid peroxidation, has emerged as a critical factor in PD pathology. This review examines the relationship between ferroptosis and PD and explores the potential of exercise as a therapeutic intervention to modulate ferroptosis and alleviate PD symptoms. Ferroptosis, distinct from other forms of cell death such as necrosis, autophagy, pyroptosis, and apoptosis, is characterized by mitochondrial shrinkage, reduced cristae, and membrane collapse, without nuclear fragmentation, DNA cleavage, or caspase activation. It is induced by the accumulation of intracellular Fe2+, which enhances lipid peroxidation and reactive oxygen species (ROS) generation, ultimately leading to cell death. Studies show disrupted iron metabolism in PD patients, with elevated iron levels in dopaminergic neurons of the substantia nigra correlating with disease severity. Iron chelation therapy has shown promise in alleviating PD symptoms by reducing brain iron levels, highlighting the significance of iron metabolism in PD pathogenesis. Lipid peroxidation, a hallmark of ferroptosis, involves the oxidation of polyunsaturated fatty acids (PUFAs) in cell membranes, compromising membrane integrity and increasing permeability. Elevated lipid peroxidation in the substantia nigra contributes to neuronal damage in PD. Enzymes such as ACSL4 and LPCAT3, crucial in PUFA metabolism, play significant roles in ferroptosis. Exercise has been shown to modulate these enzymes, potentially reducing lipid peroxidation and preventing ferroptosis in PD. Glutathione (GSH) metabolism is another crucial factor in ferroptosis regulation. GSH depletion impairs ROS detoxification, exacerbating oxidative stress and lipid peroxidation. PD patients exhibit reduced GSH levels in the substantia nigra, making dopaminergic neurons more vulnerable to oxidative damage. Exercise enhances GSH synthesis and activity, mitigating oxidative stress and ferroptosis in PD. α-Synuclein aggregation, a hallmark of PD, is closely linked to iron metabolism and oxidative stress. Excessive α‑synuclein binds to iron, promoting its aggregation and inducing ferroptosis. Exercise has been found to reduceα-synuclein accumulation and its pathological phosphorylation, potentially through the upregulation of neuroprotective proteins like DJ-1 and Irisin. These proteins enhance antioxidant defenses and facilitate α‑synuclein degradation, providing a protective effect against PD progression. Additionally, glutamate excitotoxicity, driven by dysregulated glutamate metabolism and receptor activity, contributes to ferroptosis in PD. Exercise modulates glutamate levels and receptor expression, reducing excitotoxicity and iron-induced neuronal damage. In conclusion, emerging research suggests that exercise may inhibit ferroptosis through multiple mechanisms, including regulation of iron metabolism, enhancement of antioxidant defenses, reduction of α-synuclein aggregation, and modulation of glutamate metabolism. These findings highlight the potential of exercise as a non-pharmacological intervention in the prevention and treatment of PD. Further research is needed to elucidate precise mechanisms and optimize exercise protocols for maximum therapeutic benefit.
2.Summary of experience in emergency operation of infective endocarditis
Lei CHEN ; Yunsheng YU ; Ke SI ; Tan LIU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(3):346-349
Objective To summarize the experience of infectous endocarditis(IE)emergency surgery.Methods A total of 76 patients admitted to the department of cardiovascular surgery of the First Affiliated Hospital of Soochow University from January 2019 to August 2022 were retrospectively analyzed.Summarize and share treatment experience.Results Out of 76 IE patients,55 cases(72.4%)were male and 21 patients(27.6%)were female.The ratio of male to female was 2.6∶1.The age ranged from 17-76 years,with a mean of(52.1±15.6)years.The positive rate of blood culture was 25.0%(19 cases).A total of 57 cases(75.0%)were cured,8 cases(10.5%)were discharged automatically,9 cases(11.8%)were improved,and 2 patients(2.6%)died before operation.There were 30 patients(39.5%)who underwent mitral valve surgery,24 patients(31.6%)who underwent aortic valve surgery,12 patients(15.7%)who underwent mitral and aortic valve surgery;15 patients(19.7%)with congenital heart disease,69 patients(90.8%)with rheumatic heart disease;66 patients(93.0%)with left cardiac system vegetations,4 patients(5.6%)with right cardiac systems vegetations;13 patients(17.1%)who requied emergency surgery,and no death.Conclusions The mortality of IE is high,and the current effective treatment is still surgery,but the timing of surgery is still controversial.This study summarized the experience of several cases of emergency operation and concluded that as long as the patient's condition permits,early operation can improve the survival rate of patients and improve the prognosis.
3.Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium.
Si-Nai LI ; Zi-Hao LIU ; Ming-Xue ZHOU ; Wei-Hong LIU ; Xiao-Lei LAI ; Ping LI ; Lei ZHANG ; Ju-Ju SHANG ; Sheng-Lei QIU ; Yan LOU ; Yu-Pei TAN ; Wen-Long XING ; Hong-Xu LIU
Chinese journal of integrative medicine 2023;29(12):1099-1110
OBJECTIVE:
To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.
METHODS:
A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.
RESULTS:
DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).
CONCLUSION
DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice
;
Animals
;
Tumor Suppressor Protein p53/metabolism*
;
Endothelial Cells/metabolism*
;
Exosomes/metabolism*
;
bcl-2-Associated X Protein/metabolism*
;
Myocardium/metabolism*
;
Myocardial Infarction/drug therapy*
;
Apoptosis
;
MicroRNAs/metabolism*
4.Activation of the adenosine A2A receptor at the acute stage of moderate traumatic brain injury enhances the neuroprotective effects of oxaloacetate.
Nan YANG ; Zhi-Zhong HUANG ; Si-Wei TAN ; Xing CHEN ; Yan PENG ; Yuan-Guo ZHOU ; Ya-Lei NING
Acta Physiologica Sinica 2022;74(4):505-512
The purpose of the present study was to investigate the effect of glutamate scavenger oxaloacetate (OA) combined with CGS21680, an adenosine A2A receptor (A2AR) agonist, on acute traumatic brain injury (TBI), and to elucidate the underlying mechanisms. C57BL/6J mice were subjected to moderate-level TBI by controlled cortical impact, and then were treated with OA, CGS21680, or OA combined with CGS21680 at acute stage of TBI. At 24 h post TBI, neurological severity score, brain water content, glutamate concentration in cerebrospinal fluid (CSF), mRNA and protein levels of IL-1β and TNF-α, mRNA level and activity of glutamate oxaloacetate aminotransferase (GOT), and ATP level of brain tissue were detected. The results showed that neurological deficit, brain water content, glutamate concentration in CSF, and the inflammatory cytokine IL-1β and TNF-α production were exacerbated in CGS21680 treated mice. Administrating OA suppressed the rise of both glutamate concentration in CSF and brain water content, and elevated the ATP level of cerebral tissue. More interestingly, neurological deficit, brain edema, glutamate concentration, IL-1β and TNF-α levels were ameliorated significantly in mice treated with OA combined with CGS21680. The combined treatment exhibited better therapeutic effects than single OA treatment. We also observed that GOT activity was enhanced in single CGS21680 treatment group, and both the GOT mRNA level and GOT activity were up-regulated in early-stage combined treatment group. These results suggest that A2AR can improve the efficiency of GOT and potentiate the ability of OA to metabolize glutamate. This may be the mechanism that A2AR activation in combination group augmented the neuroprotective effect of OA rather than aggravated the brain damages. Taken together, the present study provides a new insight for the clinical treatment of TBI with A2AR agonists and OA.
Adenosine A2 Receptor Agonists/therapeutic use*
;
Adenosine Triphosphate
;
Animals
;
Brain Injuries/metabolism*
;
Brain Injuries, Traumatic/metabolism*
;
Glutamic Acid
;
Mice
;
Mice, Inbred C57BL
;
Neuroprotective Agents/therapeutic use*
;
Oxaloacetic Acid/therapeutic use*
;
RNA, Messenger
;
Receptor, Adenosine A2A/metabolism*
;
Tumor Necrosis Factor-alpha/genetics*
;
Water
5.Epilepsy in Southeast Asia, how much have we closed the management gap in past two decades?
Kheng-Seang Lim ; Zhi-Jien Chia ; Moe-Zaw Myint ; Kazi Jannat Ara ; Yong-Chuan Chee ; Woon-Theng Heng ; Thanmidraaj-Kaur Balraj Singh ; Janice-Ying-Qian Ong ; Slocahnah SreeKumar ; Minh-An Thuy Lee ; Si-Lei Fong ; Chong-Tin Tan
Neurology Asia 2020;25(4):425-438
The last review on epilepsy in Southeast Asian (SEA) countries was reported in 1997. This review
aimed to update the understanding of epilepsy management in this region over the past 23 years. There
has been significant increase in the epidemiological studies which reported a prevalence of 4.3-7.7 per
1,000 populations in this region. Reversible aetiologies of epilepsy such as head injury, birth trauma,
cerebrovascular disease, and intracranial infections (neurocysticercosis or meningoencephalitis) are
still prevalent, with a surge in autoimmune encephalitis. There was a surge in genetic studies which
suggest ethnic variation. Treatment gap is still high especially in the rural and less developed areas,
and the availability and affordability of newer anti-epileptic drugs (AEDs) is still a major challenge
in SEA. Alternative medicine is a common practice but varies among different ethnic groups. AEDs
hypersensitivity especially on the association between HLA-B*1502 and carbamazepine-related severe
cutaneous reaction had been extensively studied and proven in nearly all SEA countries. However,
HLA-B*1502 screening is not widely available in SEA and the cost-effectiveness of the screening is
questionable. Stigma and its psychosocial consequences are still a major concern despite enormous
efforts to study the public attitudes towards epilepsy and change of epilepsy naming in a few countries.
The number and complexity of epilepsy surgery are progressing, but it is still under-utilized in many
SEA countries, related to cost, cultural perception and lack of facilities. More resources should also
be channelled in training adequate number of epileptologists who can spearhead epilepsy care around
the region, as well as public education and research in epilepsy. In conclusion, there is an increase in
epilepsy research in this region, gradual increase in trained neurologists and facilities, and efforts to
reduce the knowledge and treatment gap, but the epilepsy management gap is still a battle to fight.
6.How many more seizure remission can we achieve with epilepsy surgeries in a general epilepsy population?
Si-Lei Fong ; Kheng-Seang Lim ; Khine Yee Mon ; Sherrini Ahmad Bazir ; ChongTin Tan
Neurology Asia 2020;25(4):467-472
Background & Objective: We knew that 63.6% of the epilepsy population can be seizure free with
the use of anti-epileptic drugs (AED), but are unsure how many more with epilepsy surgeries. We
aimed to determine the additional remission rate achieved with epilepsy surgeries in addition to AED.
Methods: We analysed the seizure outcome among epilepsy patients seen retrospectively over oneyear period in University Malaya Medical Centre, Malaysia, which provides all levels (level 1-4) of
epilepsy cares, in response to anti-epileptic drug (AED) and epilepsy surgeries. The seizure outcome
was categorised into remission and drug-resistant, according to ILAE definition of drug resistance.
Results: There were 909 patients seen during the study period, majority with focal epilepsy (63.3%),
and Chinese (37.4%). Of those, 409 (45.0%) were in seizure remission, 238 (26.2%) had drug-resistant epilepsy and 262 (28.8%) uncertain. Only the remission and drug-resistant groups (N=647) were included in subsequent analysis. The mean age of onset in drug-resistant group was 14.8±12.3 years old, which was significantly younger than the remission group (20.8±16.8, p<0.05). There were 40 (54.8%) patients who underwent resective epilepsy surgeries (10 were lesion-negative cases). The
seizure freedom rate with epilepsy surgery was 60.0% (n=24). Overall, a total of 59.5% of patients
were in seizure remission with AED, with an additional 3.7% with epilepsy surgery.
Conclusion: There were 3.7% of epilepsy patients achieved seizure remission with epilepsy surgeries
in a general epilepsy cohort in addition to AEDs.
7.Application of the Virtual Reality-Pattern Visual Evoked Potential in Forensic Visual Acuity Evaluation.
Wei Yi TANG ; Jie Min CHEN ; Rong Rong WANG ; Si Lei TAN ; Dong Mei LIU ; Xiao Ying YU ; Hui Hua LI ; Qun Feng ZHANG ; Yan Liang SHENG ; Wen Tao XIA
Journal of Forensic Medicine 2020;36(6):762-766
Objective To explore a kind of visual evoked potential test equipment and method that is more suitable for the application of forensic clinical visual acuity evaluation. Methods Thirty-four volunteers (68 eyes) were selected, including 15 males and 19 females, aged between 20 and 40 years. Test lenses were placed before the tested eyes of volunteers to induce refractive myopia with insert method, and the diopter lenses were adjusted so that the visual acuity level of one eye of volunteers was above 0.8, and the visual acuity of the other eye was at moderate damage level (<0.3 and ≥0.1). The tests were carried out under the binocular simultaneous asynchronous stimulation mode (hereinafter referred to as "binocular mode") and monocular separate stimulation mode (hereinafter referred to as "monocular mode") of virtual reality-pattern visual evoked potential (VR-PVEP), and the amplitude of PVEP of volunteers under the two modes was compared at four spatial frequencies of 8×8, 16×16, 24×24 and 32×32. Results The differences in the amplitude of P100 wave between monocular and binocular modes at 8×8 spatial frequency had no statistical significance and the differences in amplitude of P100 wave between monocular and binocular modes at 16×16, 24×24, and 32×32 spatial frequencies had statistical significance (P<0.05). The amplitude of the same eye in monocular mode was higher than that in binocular mode. Through correlation analysis, it was found that the amplitude of P100 wave in monocular mode was moderately correlated with amplitude of P100 wave in binocular mode. Conclusion In forensic identification practice, VR-PVEP is helpful for overcoming the disturbance of poor fixation, and to increase the reliability of PVEP evaluation results. It can greatly shorten the detection time of PVEP and improve work efficiency.
Adult
;
Evoked Potentials, Visual
;
Eye
;
Female
;
Humans
;
Male
;
Reproducibility of Results
;
Virtual Reality
;
Visual Acuity
;
Young Adult
8. Analysis of Mechanism of Artesunate in Treatment of Liver Cancer Based on Metabolomics
Hui-guo WANG ; Si-yao WANG ; Xin-long HAN ; Yu-tong LI ; Li-xia YUAN ; Xiao-mei TAN ; Qing-fa TANG ; Xue-feng XING ; Fei-long CHEN ; Ya-lei YIN ; Ling TANG
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(22):78-85
Objective: To study on the antitumor mechanism of artesunate in the treatment of liver cancer based on gas chromatography-mass spectrometry (GC-MS). Method: CellTiter-Glo® Luminescent Cell Viability Assay was used to detect activity of artesunate with different concentrations (0, 12.5, 25, 50, 100 μmol·L-1) on human liver cancer Huh7, SMMC-7721 cells for 24, 48, 72 h. GC-MS was employed to analyze the changes of metabolites of artesunate in two kinds of hepatoma cells (Huh7, SMMC-7721) for 24 h. The data was preprocessed by Postrun Analysis 4.41 workstation. Partial least squares-discriminant analysis (PLS-DA) was used to analyze two sets of differential metabolites and to analyze metabolic pathways of differential metabolites based on MetaboAnalyst 3.0 software. Result: Compared with the normal group, after two kinds of liver cancer cells was treated by artesunate, a total of 39 identical metabolites in the cells have undergone significant changes, which were mainly related to five metabolic pathways,including biosynthesis of aminoacyl-transfer RNA (tRNA), metabolism of alanine, aspartic acid and glutamic acid, metabolism of glycine, serine and threonine, metabolism of arginine and proline, metabolism of glutathione. Conclusion: Artesunate (12.5-100 μmol·L-1) can inhibit the growth of liver cancer cells (Huh7, SMMC-7721), it mainly involves five metabolic pathways, which may be the pathway of artesunate against liver cancer.
9.Hyperglycemia-Associated Hemichorea-Hemiballismus with Predominant Ipsilateral Putaminal Abnormality on Neuroimaging
Si Lei FONG ; Ai Huey TAN ; Kar Foo LAU ; Norlisah RAMLI ; Shen Yang LIM
Journal of Movement Disorders 2019;12(3):187-189
No abstract available.
Neuroimaging
10.Application of PRVEP Waveform Amplitude Ratio to Evaluate Visual Acuity and Its Forensic Significance.
Xiao Ying YU ; Si Lei TAN ; Wei Yi TANG ; Jie Min CHEN ; Meng WANG ; Rui Jue LIU ; Wen Tao XIA
Journal of Forensic Medicine 2019;35(4):402-405
Objective To research the correlation between the visual acuity ratio and pattern reversal visual evoked potential (PRVEP) P100 waveform amplitude ratio of both eyes. Methods Forty-seven volunteers were selected, and the visual chart visual acuity of both eyes was measured. The visual acuity ratio of the eye with poor vision to the eye with better vision was calculated by five grade notation method. The amplitudes of P100 waveforms of both eyes were recorded respectively by using black-and-white checkerboard PRVEP and chosing 1°, 15' stimulating visual angle, and the ratio of amplitudes between the two eyes was also calculated. SPSS 20.0 software was used to analyze the correlation between the visual acuity ratio and the ratio of P100 waveform amplitudes between the two eyes. Return test and linear regression analysis with the binocular ratio of P100 waveform amplitudes as the independent variable (x) and the binocular visual acuity ratio as the dependent variable (y) were made. Results There was a positive correlation between the binocular visual acuity ratio and the ratio of P100 waveform amplitudes under 15' stimulating visual angle (Pearson correlation coefficient was 0.62, P=0.000). The fitting linear regression equation was y=0.090 x+0.846 (F=20.954, P=0.000). There was no significant correlation between the binocular ratio of visual acuity and the binocular ratio of P100 waveform amplitudes under 1° stimulating visual angle (P>0.05). Results of return test showed that there was no statistical significance in the difference between visual acuity estimated by equation and actual detected visual acuity. Conclusion In forensic appraisal of monocular injury, fitting linear regression equation of binocular visual acuity ratio and the binocular ratio of P100 waveform amplitudes under 15' stimulating visual angle, is helpful for visual acuity level estimation of the injured eye to some extent.
Evoked Potentials, Visual
;
Eye/physiopathology*
;
Humans
;
Regression Analysis
;
Vision, Ocular
;
Visual Acuity


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