1.Fibroblast Growth Factors in Parkinson’s Disease: Multi-target Neuroprotective Mechanisms Involving Neuroinflammation, Cellular Stress, and Ferroptosis
Hui WANG ; Zi-Gui ZHOU ; Teng-Teng HAN ; Chang-Zhi YANG ; Xue-Wen TIAN
Progress in Biochemistry and Biophysics 2026;53(4):855-874
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological accumulation ofα‑synuclein. Although extensive progress has been made in elucidating its pathogenesis, current therapeutic approaches remain largely symptomatic, and effective disease-modifying treatments are still unavailable. Increasing evidence indicates that PD is driven by the interaction of multiple pathological processes, including neuroinflammation, iron homeostasis dysregulation and ferroptosis, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, oxidative stress, and impaired protein homeostasis, which together contribute to neuronal vulnerability and degeneration. Fibroblast growth factors (FGFs) comprise a family of 22 ligands that play important roles in neural development, stress responses, metabolic regulation, and the maintenance of nervous system homeostasis. Recent studies have shown that several FGF family members, such as FGF1, FGF2, FGF9, and FGF21, exert neuroprotective effects in cellular and animal models of PD. These effects include the regulation of inflammatory responses, oxidative stress, iron homeostasis, cellular stress adaptation, and neuronal survival. Compared with therapeutic strategies targeting a single pathogenic pathway, FGFs appear to influence multiple disease-related processes, suggesting their potential relevance to the complex pathophysiology of PD. Experimental evidence indicates that altered FGF signaling may contribute to dopaminergic neuron dysfunction through the coordinated regulation of several interconnected mechanisms. FGFs have been reported to modulate neuroinflammation by affecting the activation of microglia and astrocytes, thereby influencing the inflammatory environment in the central nervous system. In addition, FGFs are involved in the regulation of iron homeostasis and ferroptosis, partly through antioxidant signaling pathways associated with NRF2, SLC7A11, and GPX4. Moreover, FGFs can alleviate ER stress and mitochondrial dysfunction by activating intracellular signaling pathways such as PI3K/AKT, AMPK-PGC-1α, as well as SIRT1-dependent programs, which support cellular energy metabolism and redox balance. Recent advances in single-cell and spatial transcriptomic studies further suggest that FGF signaling is not limited to neuron-intrinsic mechanisms but also involves interactions among different glial cell types. Altered FGF ligand-receptor communication between astrocytes and oligodendrocytes has been observed in PD models and is associated with increased susceptibility of dopaminergic neurons to oxidative stress and ferroptosis. These findings indicate that the biological effects of FGFs are influenced by cell type and disease stage and may vary under different pathological conditions. In this review, we summarize recent progress in understanding the roles of FGF family members in PD, with a focus on their involvement in iron homeostasis dysregulation and ferroptosis, neuroinflammation, cellular stress responses, and neuronal protection and regeneration. By integrating current evidence, this review aims to provide a clearer understanding of how FGFs participate in PD pathogenesis and to offer a theoretical basis for future studies exploring their potential value in disease-modifying therapeutic strategies.
2.Inverse Association Between Alcohol Consumption and Parkinson’s Disease Risk and Identification of RIT2 as a Linked Biomarker
Wei LU ; Xiu-Li CHENG ; Xiao-Yun PAN ; Dan-Dan YANG ; Hui-Ling ZOU ; Li-Guo DONG ; Yi-Liang WEI ; Gui-Yun CUI
Progress in Biochemistry and Biophysics 2026;53(6):1723-1733
ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (ORIVW<1) and 9 positive associations (ORIVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (ORIVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (ORIVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.
3.The first record of Anopheles messeae (Diptera: Culicidae) parasitized by water mites in China
Xue-ru CHEN ; Wen-zhen YAO ; Yu-hao LI ; Gui-chang LI ; Tao MENG ; Qun-ling FENG ; Xin-hui LIU ; Li-hong QIAO ; Xiang-ting WU ; Xue-feng ZHANG ; Cheng-lin LI ; Xue-cheng DONG ; Da-wei WANG ; Xiao-yan SI ; Yu-hong GUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):53-57
Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.
4.Association of angiotensin Ⅱ type 1 receptor autoantibody and sperm motility in human semen.
Dao-Qin TU ; Yu-Huan YANG ; Gui-Fang YANG ; Yi-Nan ZHANG ; Yao CHEN ; Xue-Ming LI ; Yu-Hui SHI ; Xiao-Li YANG ; Feng WANG
National Journal of Andrology 2025;31(5):387-394
OBJECTIVE:
To investigate the relationship between angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) and semen parameters. Methods: The semen samples of 820 male patients who were treated in the Reproductive Medicine Center of Taiyuan Central Hospital from August 2022 to August 2023 were retrospectively analyzed. The levels of AT1-AA and Ang Ⅱ of semen were detected by ELISA, and the function of AT1-AA was detected by cardiomyocyte beating assay in suckling rats. The patients were divided into low group, median group and high group according to the OD values of AT1-AA. The differences in general data and semen parameters between different groups were analyzed. And the correlation between AT1-AA level and semen parameters in semen of all study subjects was analyzed by the method of Spearman analysis. And the relationships between AT1-AA OD value, Ang Ⅱ level and semen parameters in the AT1-AA high value group were analyzed as well.
RESULTS:
AT1-AA was present in semen with good function. There was no significant difference in the general data of patients in different AT1-AA levels (P>0.05). In the comparison of semen parameters among the groups with different levels of AT1-AA, there were differences in sperm concentration, PR concentration, NP%, and ALH among the three groups (P<0.05). And AT1-AA OD value was positively correlated with total sperm count, sperm concentration, PR concentration, and NP%, and negatively correlated with semen volume (P<0.05). In the AT1-AA high value group, the OD value of AT1-AA in semen was negatively correlated with inactive sperm, and positively correlated with total motility ([PR+NP]%), curve rate, mean path rate, and ALH. However, there was no correlation between the level of Ang Ⅱ in semen and semen parameters (P>0.05).
CONCLUSION
The presence of AT1-AA in semen may be associated with the promotion of sperm motility.
Male
;
Humans
;
Autoantibodies
;
Sperm Motility
;
Semen
;
Retrospective Studies
;
Receptor, Angiotensin, Type 1/immunology*
;
Animals
;
Rats
;
Angiotensin II
;
Adult
;
Sperm Count
;
Semen Analysis
;
Receptor, Angiotensin, Type 2/immunology*
6.Clinical study on the treatment of avulsion fractures of the posterior cruciate ligament of the tibial platform with a modified minimally invasive transmuscular approach on the posterior side of the knee joint
Xi CHEN ; Hui LIU ; Zhihan ZHANG ; Aihemaiti SHAMI ; Ning GUI ; Abulimiti DILIHUMAER ; Jinhai TAN ; Shengxiang TAO
Journal of Clinical Surgery 2025;33(4):379-382
Objective To explore a better surgical approach for the surgical treatment of avulsion fractures of the posterior cruciate ligament of the tibial plateau.Methods From July 2014 to May 2024,A total of 29 cases of avulsion fractures at the insertion point of the posterior cruciate ligament of the tibial platform were admitted to our department.They were divided into two groups according to different surgical approaches.There were 16 cases in group A,which adopted the modified posterior approach,and 13 cases in group B,which adopted the conventional posterior approach.The therapeutic effects of the two groups of patients were evaluated by using the Lysholm knee score scale after surgery and the KOOS knee injury and osteoarthritis outcome scoring system.Results All patients were followed up for 12 to 14 months,with an average of(12.6±0.3)months.No serious adverse complications such as non-healing of the surgical site occurred in group A.In group B,there was 1 case of delayed wound healing and 8 cases of knee joint pain during movement.The Lysholm knee joint score and KOOS knee joint outcome score of patients in group A at 12 months after the operation were(88.65±9.23)points and(90.48±6.84)points respectively,and those in group B were(63.98±10.77)points and(69.37±9.01)points respectively.Both groups in group A were more satisfied than those in group B,and the difference was statistically significant(P<0.05).Conclusion For patients with avulsion fractures of the insertion point of the posterior cruciate ligament of the tibial platform,the modified minimally invasive penetrating muscle approach on the posterior side of the knee joint can reduce related complications such as excessive intraoperative bleeding,internal relaxation of the knee joint,and poor postoperative wound healing,enabling early functional exercise for patients and achieving a better prognosis.
7.Influence of Oatp4c1-P-gp transmembrane transport system in the kidneys of obese mice on the pharmacokinetics of digoxin
Jing-wen MEN ; Lu SUN ; Hao-ran YUE ; Zhao-yue DUAN ; Hui-nan HOU ; Ting GUI ; Jun-hong XIN ; Zhi-bo GAI
Chinese Pharmacological Bulletin 2025;41(7):1318-1324
Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.
8.Imaging findings of pediatric atypical teratoid/rhabdoid tumor in the central nervous system
Ting GUI ; Hui ZHENG ; Jinning LI ; Caiting CHU ; Ming LIU ; Yuzhen ZHANG ; Yuhua LI ; Dengbin WANG
Journal of Practical Radiology 2025;41(11):1857-1860
Objective To explore the imaging findings of atypical teratoid/rhabdoid tumor(AT/RT)in the central nervous sys-tem of children and to improve the understanding of this disease.Methods A retrospective analysis was conducted on the imaging data of 55 children with AT/RT confirmed by pathology.Results Among the 55 AT/RT children,74.5%were under 3 years old,with a male-to-female ratio of 1.5∶1.Intracranial AT/RT appeared hyperdense or slightly hyperdense on CT scans and accompa-nied by calcification or hemorrhage occasionally.32 cases showed peripheral cystic changes in MRI images.38 cases showed heteroge-neous enhancement,9 cases showed ring-like or band-like enhancement.13 cases showed cerebrospinal fluid dissemination.The mean minimum apparent diffusion coefficient(ADC)value was(0.61±0.11)× 10-3mm2/s.Spinal AT/RT manifested as solitary or mul-tiple intramedullary and/or extradural lesions on MRI,which showed unclear boundary from the spinal cord.Hemorrhage within or at the edge of the lesion was seen in 2 cases,involvement of nerve roots and adjacent muscle tissues in 3 cases,and cerebrospinal fluid dissemination of the intracranial and spinal cord at varying degrees in 5 cases.Conclusion The imaging findings of pediatric AT/RT in the central nervous system are diverse,combining imaging characteristics with age of onset facilitates the accurate diagnosis.
9.The effect of salidroside derivative pOBz on angiogenesis after ischemic stroke by regulating Notch signaling pathway
Jing-quan CHEN ; Yu-ting JIANG ; Xue-rui ZHENG ; Hui-ling WU ; Qing-qing WU ; Zheng-shuang YU ; Wen-fang LAI ; Gui-zhu HONG
Chinese Pharmacological Bulletin 2025;41(12):2253-2259
Aim To study the effect of p-benzoyl sali-droside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was em-ployed to detect CD31,NICD,and Hes-1 protein ex-pression,while immunofluorescence staining was ap-plies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz con-centrations(0.01,0.1,1 μmol·L-1),the CCK-8 as-say was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administra-tion,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregu-lated CD31,NICD,and Hes-1 protein expression(P<0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angio-genesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P<0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angio-genesis in HUVEC,and its mechanism involves activa-tion of the Notch signaling pathway.
10.Application Value of Vertebral CT Values in Fresh and Old Fractures Vertebral Bodies of Patients with Osteoporotic Vertebral Compression Fractures
Feng WANG ; Wei-sheng PENG ; Gui-liu CHEN ; Na DENG ; Xiao-bing HAN ; Hui-liang CAI ; Qiu-xiang CHEN
Progress in Modern Biomedicine 2025;25(19):3179-3185
Objective:To explore the value of using computed tomography(CT)values to distinguish fresh and old fractures vertebral bodies in osteoporotic vertebral compression fractures(OVCF).Methods:Retrospective analysis of clinical data of 101 OVCF patients in our hospital from September 2022 to September 2023.Kappa test for consistency between magnetic resonance imaging(MRI)and vertebral CT values in distinguished fresh or old OVCF.The difference of CT values between fresh,old fractures and adjacent normal vertebral bodies were compared.The diagnostic efficiency was analyed by receiver operating characteristic(ROC)curve.Results:There was a high consistency between vertebral CT values and MRI in the diagnosis of OVCF in fresh and old fractures(Kappa value=0.934).There was a difference in difference of CT values between adjacent normal vertebral bodies and fresh fractures vertebral bodies(P<0.05).There was a difference in difference of CT values of fresh fractures vertebral bodies and old fractures vertebral bodies(P<0.05).The ROC curve analysis results showed that,the combined measurement of CT values of fresh and old fractured vertebral bodies has an area under the curve(AUC)of 0.723,which was higher than alone measurement of the CT values of fresh fractured vertebral bodies and old fractured vertebral bodies of 0.536 and 0.610(Z=2.548,2.605,2.841,P<0.05).Conclusion:CT values of vertebral bodies show high consistency in distinguish fresh and old fractures of OVCF compared to MRI findings,and the diagnostic efficiency of combine detection is relatively high.


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