1.Skeleton Binding Protein 1 of Plasmodium berghei Influences Deformability and Cytoskeletal Ultrastructure of Infected Erythrocyte
Xin-Yue GUO ; Huan-Qi ZHAO ; Yan-Xuan ZHONG ; Ru-Meng JIANG ; Yao-Xian LI ; Lei-Ting PAN ; Qian WANG ; Xiao-Yu SHI
Progress in Biochemistry and Biophysics 2026;53(4):1015-1027
ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.
2.Correlation analysis of inflammatory markers (NLR/PLR/SII) with the severity of intrauterine adhesions
Ying WANG ; Xuan XU ; Longyu ZHANG ; Rong WU ; Jingjing HU ; Wenjuan YANG ; Xiao WU ; Zhaolian WEI
Acta Universitatis Medicinalis Anhui 2026;61(1):146-150
ObjectiveTo investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) and the severity of intrauterine adhesions (IUA). MethodsThe retrospective study included 380 patients who underwent transcervical resection of adhesions (TCRA) from December 2019 to March 2025. Based on the American Fertility Society (AFS) classification, patients were divided into mild (n=61), moderate (n=225), and severe (n=94) groups. NLR, PLR, and SII were calculated from preoperative blood tests. Statistical analyses included Kruskal-Wallis test and ordinal Logistic regression. ResultsNLR, PLR, and SII were significantly higher in the severe IUA group compared to the mild group (P<0.05), with SII showing the strongest predictive ability (OR=1.004, P=0.001). The number of intrauterine procedures was an independent risk factor (OR=1.27/level, P=0.016). The predictive model [Logit(P)=-0.676+0.241×operation times+0.004×SII] effectively identified severe IUA cases. ConclusionInflammatory markers (particularly SII) are correlated with IUA severity and may serve as non-invasive tools for clinical assessment.
3.Analysis of the effect of dosimeter wearing position on effective dose estimation among interventional radiology workers
Xuanrong ZHANG ; Wen GUO ; Xian XUE ; Pin GAO ; Kaiyi WANG ; Xuan ZHANG ; Yanqiu DING ; Xiao LUO ; Wenfang MENG ; Jun CHAO
Chinese Journal of Radiological Health 2025;34(5):687-694
Objective To evaluate the influence of the wearing position of dosimeters outside lead aprons on effective dose estimation for interventional radiology workers, analyze the differences between single and double dosimeter methods in effective dose estimation, and provide a reference for the personal dose monitoring of interventional radiology workers. Methods This study employed a combined approach of on-site monitoring and Monte Carlo simulation to evaluate the impact of the wearing position of dosimeters outside lead aprons on effective dose estimation, as well as the differences between effective doses measured using single and double dosimeters. Interventional radiology workers wore dosimeters at three positions: the neck outside the lead collar, the left chest outside the lead apron, and inside the lead apron. Effective doses were estimated using the single and double dosimeter methods specified in GBZ 128-2019 Specifications for individual monitoring of occupational external exposure, and the impact of different wearing positions on the estimation results was compared. Geant4 Monte Carlo simulations were used to model dose distributions at the neck outside the lead collar and at the left chest outside the lead apron for operators performing cardiovascular interventions under tube voltages of 70, 80, 90, and 100 kVp and exposure angles of posteroanterior (PA), anteroposterior (AP), and left anterior oblique 45° (LAO45°) positions. The study assessed the impact of dosimeter wearing position on effective dose estimation. Results Monte Carlo simulations demonstrated that neck doses consistently exceeded left chest doses across different tube voltages and exposure angles, with neck-to-chest dose ratios of 0.80-0.90. Under identical tube voltage conditions, AP showed the highest doses, followed by LAO45°, and PA demonstrated the lowest doses. The single and double dosimeter methods exhibited consistent patterns in effective dose estimation. Single dosimeter method generally yielded higher effective doses with relative deviations of 9.9% to 83%, though these deviations decreased under high tube voltages. Field monitoring data indicated that most interventional radiology workers maintained relative deviations between single and double dosimeter calculations below 6%, with neck-to-chest dose ratios of 0.95-1.1. The estimation patterns remained consistent across both methods, though single dosimeter method showed slightly higher results. Conclusion Under PA, AP, or LAO45°, the doses at the neck consistently exceeded those at the left chest. Therefore, when wearing lead protective equipment, the dosimeter should be properly positioned at the neck outside the lead collar to accurately reflect the radiation doses of surgeons. Some interventional radiology workers improperly positioned the dosimeter (intended at the neck outside the lead collar) at the left chest outside the lead apron, and this may result in an underestimation of the effective dose.
4.Effects of different exercise interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats
Shujuan HU ; Ping CHENG ; Xiao ZHANG ; Yiting DING ; Xuan LIU ; Rui PU ; Xianwang WANG
Chinese Journal of Tissue Engineering Research 2025;29(2):269-278
BACKGROUND:Carboxylesterase 1 and inflammatory factors play a crucial role in regulating lipid metabolism and glucose homeostasis.However,the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats remain to be revealed. OBJECTIVE:To investigate the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats. METHODS:Thirty-two 8-week-old male Sprague-Dawley rats were randomly divided into normal control group(n=12)and modeling group(n=20)after 1 week of adaptive feeding.Rat models of type 2 diabetes mellitus were prepared by high-fat diet and single injection of streptozotocin.After successful modeling,the rats were randomly divided into diabetic control group(n=6),moderate-intensity exercise group(n=6)and high-intensity intermittent exercise group(n=6).The latter two groups were subjected to treadmill training at corresponding intensities,once a day,50 minutes each,and 5 days per week.Exercise intervention in each group was carried out for 6 weeks.After the intervention,ELISA was used to detect blood glucose and blood lipids of rats.The morphological changes of skeletal muscle were observed by hematoxylin-eosin staining.The mRNA expression levels of carboxylesterase 1 and inflammatory cytokines were detected by real-time quantitative PCR.The protein expression levels of carboxylesterase 1 and inflammatory cytokines were detected by western blot and immunofluorescence. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,insulin resistance index in the diabetic control group were significantly increased(P<0.01),insulin activity was decreased(P<0.05),and the mRNA and protein levels of carboxylesterase 1,never in mitosis gene A related kinase 7(NEK7)and interleukin 18 in skeletal muscle tissue were upregulated(P<0.05).Compared with the diabetic control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,and insulin resistance index in the moderate-intensity exercise group and high-intensity intermittent exercise group were down-regulated(P<0.05),and insulin activity was increased(P<0.05).Moreover,compared with the diabetic control group,the mRNA level of NEK7 and the protein levels of carboxylesterase 1,NEK7 and interleukin 18 in skeletal muscle were decreased in the moderate-intensity exercise group(P<0.05),while the mRNA levels of carboxylesterase 1,NEK7,NOD-like receptor heat protein domain associated protein 3 and interleukin 18 and the protein levels of carboxylesterase 1 and interleukin 18 in skeletal muscle were downregulated in the high-intensity intermittent exercise group(P<0.05).Hematoxylin-eosin staining showed that compared with the diabetic control group,the cavities of myofibers in the moderate-intensity exercise group became smaller,the number of internal cavities was reduced,and the cellular structure tended to be more intact;the myocytes of rats in the high-intensity intermittent exercise group were loosely arranged,with irregular tissue shape and increased cavities in myofibers.To conclude,both moderate-intensity exercise and high-intensity intermittent exercise can reduce blood glucose,lipid,insulin resistance and carboxylesterase 1 levels in type 2 diabetic rats.Moderate-intensity exercise can significantly reduce the expression level of NEK7 protein in skeletal muscle,while high-intensity intermittent exercise can significantly reduce the expression level of interleukin 18 protein in skeletal muscle.In addition,the level of carboxylesterase 1 is closely related to the levels of NEK7 and interleukin 18.
5.Mechanism of Chaijin Jieyu Anshen Formula in regulating synaptic damage in nucleus accumbens neurons of rats with insomnia complicated with depression through TREM2/C1q axis.
Ying-Juan TANG ; Jia-Cheng DAI ; Song YANG ; Xiao-Shi YU ; Yao ZHANG ; Hai-Long SU ; Zhi-Yuan LIU ; Zi-Xuan XIANG ; Jun-Cheng LIU ; Hai-Xia HE ; Jian LIU ; Yuan-Shan HAN ; Yu-Hong WANG ; Man-Shu ZOU
China Journal of Chinese Materia Medica 2025;50(16):4538-4545
This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals
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Male
;
Rats
;
Nucleus Accumbens/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
;
Depression/complications*
;
Membrane Glycoproteins/genetics*
;
Rats, Sprague-Dawley
;
Sleep Initiation and Maintenance Disorders/complications*
;
Neurons/metabolism*
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Receptors, Immunologic/genetics*
;
Signal Transduction/drug effects*
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Synapses/metabolism*
6.Imaging changes of the intervertebral disc after posterior cervical single door enlarged laminoplasty for cervical spinal stenosis with disc herniation.
Yan-Dong ZHANG ; Xu-Hong XUE ; Sheng ZHAO ; Gui-Xuan GE ; Xiao-Hua ZHANG ; Shi-Xiong WANG ; Ze GAO
China Journal of Orthopaedics and Traumatology 2025;38(6):572-580
OBJECTIVE:
To explore prevalence, incidence and possible factors of immediate herniated discs after posterior cervical expansive open-door laminoplasty (EODL).
METHODS:
Totally 29 patients with cervical spinal stenosis and intervertebral disc herniation who underwent EODL from October 2020 to December 2021 were collected, including 24 males and 5 females, aged from 43 to 81 years old with an average of (61.3±9.0) years old;the courses of disease ranged from 1 to 120 months with an average of (36.4±37.0) months. Three or more intervertebral discs on C3-C7 were observed. The clinical efficacy was evaluated according to Japanese Orthopaedic Association (JOA) score before operation, 3 days and 1, 3, 6 and 12 months after operation, respectively. The changes of herniated disc before and after operation were measured by multipoint area method and two-dimensional distance method, and incidence and percentage of herniated disc regression were further calculated. Cervical imaging parameters such as Cobb angle (C3-C7), intervertebral angle, T1 slope (T1S), spinal canal sagittal diameter, K-line angle, dural sac sagittal diameter were measured and compared before and after operation. Pearson correlation was used to analyze correlation between cervical sagittal imaging parameters and disc herniation changes before and after operation.
RESULTS:
All patients obtained grade A wound healing, and 14 of them were followed up for 3(1.00, 5.25) months. There were no immediate or long-term postoperative complications. Totally 101 herniated intervertebral discs were measured, of which 79 regression numbers were obtained by area measurement. The number of intervertebral disc regressions by distance measurement was 77. There was no statistically significant difference in Cobb angle, intervertebral angle, T1S and K-line angle of C3-C7 (P>0.05), however, there were statistically significant differences in sagittal diameter of spinal canal, sagittal diameter of dural sac, and JOA score before and after operation(P<0.05). The regression ratio of disc herniation ranged from 5% to 50%, and regression ratio of disc herniation was greater than 25% in 45.57%(36/79). Disc herniation in C4,5 was positively correlated with sagittal plane diameter in C5(r=0.423, P=0.028). There was a negative correlation between changes of C3,4 and C3,4 intervertebral angle (r=-0.450, P=0.041). The improvement rate of cervical JOA score immediately after operation was (59.54±15.07) %, and postoperative follow-up improved to (76.57±14.66) %.
CONCLUSION
Herniated disc regression immediately after EODL is a common occurrence, and EODL should be selected as far as possible under the premise of satisfying surgical indications. The regression of disc herniation is positively correlated with spinal canal sagittal diameter, and spinal canal should be enlarged as far as possible in the appropriate scope during EODL, so as to create more opportunities and conditions for disc regression and achieve better clinical results.
Humans
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Female
;
Male
;
Intervertebral Disc Displacement/diagnostic imaging*
;
Spinal Stenosis/diagnostic imaging*
;
Laminoplasty/methods*
;
Middle Aged
;
Aged
;
Cervical Vertebrae/diagnostic imaging*
;
Adult
;
Aged, 80 and over
;
Intervertebral Disc/surgery*
7.Epidemiological characteristics of respiratory syncytial virus infection in children in Hebei Province.
Xuan WANG ; Su-Kun LU ; Jian-Hua LIU ; Jin-Feng SHUAI ; Kun-Ling HUANG ; Bo NIU ; Li-Jie CAO ; Xiao-Wei CUI
Chinese Journal of Contemporary Pediatrics 2025;27(10):1199-1204
OBJECTIVES:
To study the epidemiological characteristics of respiratory syncytial virus (RSV) infection in hospitalized children with community-acquired pneumonia (CAP) in Hebei Province.
METHODS:
Hospitalized children with CAP who tested positive for RSV and were admitted to Hebei Children's Hospital from various cities and counties across Hebei Province between January 2019 and December 2023 were included in the study. Clinical data were collected and analyzed to assess epidemiological characteristics.
RESULTS:
The clinical data of 43 978 children with CAP were collected, with an overall RSV detection rate of 25.98%. The detection rate was higher during the implementation of non-pharmaceutical interventions (NPIs) (30.60%) than in the non-NPIs period. Winter and spring were the primary epidemic seasons for RSV each year except in 2022. The detection rate in males (26.62%) was higher than in females (25.06%) (P<0.001). The highest detection rate (59.18%) was found in infants aged 29 days to <1 year. Single RSV infection was more common, with rhinovirus being the most frequent co-infection.
CONCLUSIONS
The overall RSV detection rate in Hebei Province is influenced by NPIs, being higher during their implementation. RSV predominantly circulates in winter and spring. The detection rate of RSV is higher in males and infants. RSV infection is primarily single, most often co-occurring with rhinovirus.
Humans
;
Respiratory Syncytial Virus Infections/epidemiology*
;
Female
;
Male
;
Infant
;
Child, Preschool
;
Seasons
;
China/epidemiology*
;
Infant, Newborn
;
Community-Acquired Infections/epidemiology*
;
Child
8.Molecular Biological Mechanism and Transfusion Strategy of a Jk(a-b-) Family.
Xiao-Yan LI ; Qiong-Fei DENG ; Xiao-Li LAI ; Dan-Dan CHEN ; Dan WANG ; Xuan ZENG
Journal of Experimental Hematology 2025;33(3):869-874
OBJECTIVE:
To investigate the molecular mechanism and explore blood transfusion strategies for a proband exhibiting the JK (a-b-) phenotype and anti-JK3 high frequency antigen antibody and her eight family members.
METHODS:
The Kidd blood phenotype and irregular antibodies in a family were identified by serologic tests. Exon 4-11 and intron region of SLC14A1 gene were sequenced by Sanger method.
RESULTS:
The combination of the gene JK*B (c.499A>G,c.512G>A,c.588A>G) and gene JK*B (c.342-1G>A,588A>G) in this family were considered to result in the JK (a-b-) phenotype in two members. The members carrying gene JK*A(c.130G>A,588A>G) all present serological JKa+W. Members carrying gene JK*B (c.499A>G,c.588A>G) all present serological JKb+W, which has not been previously reported to cause antigenic weakening. The proband with JK (a-b-) phenotype produced anti-JK3 antibodies, the hospital formulated a number of blood preparation strategies for the patient and she was discharged after recovery.
CONCLUSION
In this study, the molecular mechanism of JK (a-b-) in this family was identified, the transfusion strategy of rare blood group was established in our institution preliminary, and the necessity of establishing a rare blood group bank was revealed in this region. It is suggested that JK*B (c.499A>G,c.588A>G) may be a new genetic pattern leading to the weakening of Kidd antigenicity, which lays a foundation for the study of population genetics.
Humans
;
Blood Transfusion
;
Female
;
Kidd Blood-Group System/genetics*
;
Phenotype
;
Pedigree
9.Qishen Granules Modulate Metabolism Flexibility Against Myocardial Infarction via HIF-1 α-Dependent Mechanisms in Rats.
Xiao-Qian SUN ; Xuan LI ; Yan-Qin LI ; Xiang-Yu LU ; Xiang-Ning LIU ; Ling-Wen CUI ; Gang WANG ; Man ZHANG ; Chun LI ; Wei WANG
Chinese journal of integrative medicine 2025;31(3):215-227
OBJECTIVE:
To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation.
METHODS:
In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions.
RESULTS:
QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism.
CONCLUSIONS
QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals
;
Myocardial Infarction/physiopathology*
;
Male
;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
;
Rats, Sprague-Dawley
;
Glucose/metabolism*
;
Drugs, Chinese Herbal/therapeutic use*
;
Energy Metabolism/drug effects*
;
Rats
;
Fatty Acids/metabolism*
;
Myocardium/pathology*
10.Augmentation of PRDX1-DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation.
Wenzhen DANG ; Xiaomin WANG ; Huaying LI ; Yixuan XU ; Xinyu LI ; Siqi HUANG ; Hongru TAO ; Xiao LI ; Yulin YANG ; Lijiang XUAN ; Weilie XIAO ; Dean GUO ; Hao ZHANG ; Qiong WU ; Jie ZHENG ; Xiaoyan SHEN ; Kaixian CHEN ; Heng XU ; Yuanyuan ZHANG ; Cheng LUO
Acta Pharmaceutica Sinica B 2025;15(8):3997-4013
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

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