1.Roles and research progress of the SLC13A5-driven metabolic-inflammatory axis in metabolic diseases, cancers and neurological disorders
Yanzhen LI ; Ziy ZHANG ; Wenjun HU ; Yitong TAO ; Zhixia QIU
Journal of China Pharmaceutical University 2026;57(4):443-452
SLC13A5 (solute carrier family 13 member 5) is an important transporter that mediates the transmembrane uptake of extracellular citrate. By regulating cytosolic citrate and acetyl-CoA levels, SLC13A5 participates in energy metabolism, lipid synthesis, inflammatory responses, and the maintenance of neuronal homeostasis. This review focuses on the SLC13A5-driven metabolic–inflammatory axis and systematically summarizes its roles and underlying mechanisms in various diseases, as well as recent advances in targeted interventions. SLC13A5-mediated citrate metabolic reprogramming affects lipid synthesis, oxidative stress, and inflammatory signaling, thereby establishing a regulatory network that links metabolic dysfunction with inflammatory responses. In metabolic diseases, upregulated SLC13A5 promotes hepatic de novo lipogenesis, exacerbates insulin resistance, and drives the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) toward inflammatory and fibrotic stages. In inflammation-related diseases, increased SLC13A5 expression enhances citrate metabolic flux, promotes the production of inflammatory mediators, and amplifies inflammatory responses. In cancer, SLC13A5 contributes to metabolic reprogramming and the maintenance of an inflammatory tumor microenvironment, thereby supporting tumor cell growth and proliferation. In the nervous system, loss of SLC13A5 function or abnormal SLC13A5 expression disrupts neuronal energy metabolism, neurotransmitter homeostasis, and neural network function, leading to epilepsy and neurodevelopmental disorders. This review further summarizes SLC13A5-targeted strategies, including small-molecule inhibitors, antisense oligonucleotides, and gene replacement therapy, and discusses the translational challenges such as tissue selectivity, central nervous system safety risks, species differences, and limited delivery efficiency. This review provides a theoretical basis for investigating the mechanisms of SLC13A5-related diseases and developing precision therapeutic strategies.
2.Construction of circular RNA vaccine against porcine reproductive and respiratory syndrome virus and optimization of circularization conditions
Chunhao TAO ; Ying HUANG ; Zhen WANG ; Yitong JIANG ; Hongfei ZHU ; Hong JIA
Chinese Journal of Veterinary Science 2025;45(5):896-904
In order to establish a highly efficient,convenient,and effective circular RNA(circRNA)vaccine preparation system,enhanced green fluorescent protein(EGFP)circRNA was constructed using permuted intron exon(PIE)strategy based on type Ⅰ introns.Then,circRNA circularization rates of RNA after in vitro transcription(IVT),primary circularization(IVC1),and secondary circularization(IVC2)were compared after purification.The constructed circRNA system was fur-ther applied to porcine reproductive and respiratory syndrome virus(PRRSV),and two circRNAs based on PRRSV GP5 protein were constructed and developed for in vitro expression.Results showed that circularization rates and protein expression effects of EGFP circRNA in IVC1 RNA and IVC2 RNA were similar,but both were significantly better than those of IVT RNA.Purity of EGFP circRNA reached 74%,and purities of two PRRSV GP5 protein circRNAs constructed using this preparation system were 71%and 64%,respectively.Western blot and indirect immunofluo-rescence assay(IFA)results indicated that both of the PRRSV GP5 protein circRNAs were suc-cessfully expressed.The results demonstrated that an easy-to-operate,low-cost circRNA prepara-tion system with high circularization rate was successfully constructed.Two PRRSV GP5 protein circRNA vaccines were successfully prepared using this system and expressed efficiently,which provides a reference for the development of animal circRNA vaccines and novel candidate vaccines against PRRSV.
3.Construction of circular RNA vaccine against porcine reproductive and respiratory syndrome virus and optimization of circularization conditions
Chunhao TAO ; Ying HUANG ; Zhen WANG ; Yitong JIANG ; Hongfei ZHU ; Hong JIA
Chinese Journal of Veterinary Science 2025;45(5):896-904
In order to establish a highly efficient,convenient,and effective circular RNA(circRNA)vaccine preparation system,enhanced green fluorescent protein(EGFP)circRNA was constructed using permuted intron exon(PIE)strategy based on type Ⅰ introns.Then,circRNA circularization rates of RNA after in vitro transcription(IVT),primary circularization(IVC1),and secondary circularization(IVC2)were compared after purification.The constructed circRNA system was fur-ther applied to porcine reproductive and respiratory syndrome virus(PRRSV),and two circRNAs based on PRRSV GP5 protein were constructed and developed for in vitro expression.Results showed that circularization rates and protein expression effects of EGFP circRNA in IVC1 RNA and IVC2 RNA were similar,but both were significantly better than those of IVT RNA.Purity of EGFP circRNA reached 74%,and purities of two PRRSV GP5 protein circRNAs constructed using this preparation system were 71%and 64%,respectively.Western blot and indirect immunofluo-rescence assay(IFA)results indicated that both of the PRRSV GP5 protein circRNAs were suc-cessfully expressed.The results demonstrated that an easy-to-operate,low-cost circRNA prepara-tion system with high circularization rate was successfully constructed.Two PRRSV GP5 protein circRNA vaccines were successfully prepared using this system and expressed efficiently,which provides a reference for the development of animal circRNA vaccines and novel candidate vaccines against PRRSV.
4.Analysis of risk factors for the occurrence and aggravation of lower back pain in Parkinson′s disease patients
Lei SHEN ; Qiang WANG ; Yitong XIONG ; Junfeng SHI ; Zhenhuan JIANG ; Chenjun ZHAI ; Tao JIANG
Journal of Chinese Physician 2024;26(9):1322-1327
Objective:To explore the independent risk factors for the occurrence and aggravation of lower back pain (LBP) in patients with Parkinson′s disease (PD), in order to provide reference for clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the case data of 309 PD patients who visited the Affiliated Yixing Hospital of Jiangsu University from June 2018 to May 2020. The KING Parkinson′s Disease Pain Scale (KPPS) was used to quantitatively evaluate the LBP of PD patients, who were divided into LBP group and Non LBP group. The general clinical data, PD related data, and imaging data of the two groups were compared and analyzed. Binary logistic regression analysis was used to evaluate independent risk factors for LBP in PD patients. Pearson correlation analysis was conducted between KPPS scores and various factors, and linear regression analysis was used to identify the relevant risk factors that exacerbate LBP in PD patients.Results:Compared with the Non LBP group, the LBP group had lower bone mineral density (BMD) and a lower proportion of patients who engaged in daily exercise. The difference between the two groups was statistically significant (all P<0.05). Compared with the Non LBP group, patients in the LBP group had a longer course of illness, higher stiffness scores, a higher proportion of patients with fluctuating symptoms, higher UPDRS-Ⅲ scores, and a higher proportion of patients with thoracolumbar fascial injury (TLFI) and lumbar sagittal imbalance. The differences between the two groups were statistically significant (all P<0.05). The results of binary logistic regression analysis showed that combined TLFI ( OR=2.773, 95% CI: 1.219-6.309, P=0.015), combined lumbar sagittal imbalance ( OR=4.835, 95% CI: 2.244-10.421, P<0.001), and lower BMD ( OR=2.818, 95% CI: 1.767-4.493, P<0.001) were risk factors for LBP in PD patients. The KPPS score was correlated with BMD and TLFI ( r=-0.146, 0.294, all P<0.05). The linear regression results showed that the merged TLFI ( B=2.271, β=0.285, P<0.001) was positively correlated with KPPS score, indicating a risk factor. Conclusions:The combination of TLFI, lumbar sagittal imbalance, and lower BMD is closely related to the occurrence of LBP in PD patients, and the combination of TLFI is an independent risk factor for exacerbating LBP symptoms. Clinical attention should be paid to the prevention and treatment of TLFI in PD patients.
5.A multicenter study on the clinical features and risk factors of poor prognosis in neonatal necrotizing enterocolitis
Yueju CAI ; Liuhong QU ; Wei LI ; Xue FENG ; Liya MA ; Bingyan YANG ; Ping WANG ; Juan TANG ; Weiming YUAN ; Yanbin LI ; Xiaowen CHEN ; Zhe ZHANG ; Ning ZHAO ; Xiaohong HUANG ; Li TAO ; Mou WEI ; Heng SU ; Weichi DENG ; Kangcheng HE ; Yitong WANG ; Jinxing FENG ; Di GAO ; Yan HUANG ; Wei ZHOU
Chinese Journal of Applied Clinical Pediatrics 2019;34(1):24-29
Objective To explore the clinical features and risk factors of poor prognosis in neonatal necrotizing enterocolitis(NEC).Methods A retrospective study was carried out in the infants with NEC admitted to 6 cooperative hospitals in Guangdong Province between January 2005 and December 2014.The clinical features and risk factors of poor prognosis in preterm and full-term infants diagnosed NEC,early onset and late onset NEC were analyzed.Results A total of 449 cases who met the criteria were admitted during the study time.The mortality was 23.6% (106/449 cases),of which the preterm group was 24.6% (58/238 cases) while the full-term group was 22.7% (48/211 cases),the early onset group was 22.1% (45/204 cases) while the late onset group was 24.3% (57/235 cases).The median number of NEC onset in preterm group was 11 d after birth while the number of the full-term group was 6 d.Full-term infants who diagnosed NEC were more likely to manifest themselves as abdominal distension (52.1% vs.42.0%,x2 =4.597,P =0.032),vomiting(36.5% vs.17.2%,x2 =21.428,P =0.000) and bloody stool(30.3% vs.21.4%,x2 =4.653,P =0.031);but in the onset of NEC,preterm infants more likely to have feeding intolerance (21.0% vs.12.8%,x2=5.309,P =0.021).The early onset group of full-term NEC was much common in twins or multiplets(9.4% vs.1.1%,x2 =6.226,P =0.013),which rate of surgical therapy was much higher (41.0% vs.27.0%,P =0.036) and the breast-feeding rate before NEC was lower than the late onset group(14.5% vs.32.6%,x2 =9.500,P =0.002),the differences were statistically significant.The gestational age and birth weight were bigger in the early onset group of preterm NEC[(33.8 ±2.5) weeks vs.(32.2 ±2.8) weeks,t =4.261,P =0.000;(2.1 ±0.5) kg vs.(1.7 ± 0.5) kg,t =4.735,P =0.000)],but length of stay was shorter than the late onset group (18.0 d vs.26.5 d,P =0.000).Logistic regression analysis showed that the risk factors of poor prognosis of full-term NEC were shock,peritonitis and sepsis;while risk factors of poor prognosis of preterm NEC were small for gestational age infant,pulmonary hemorrhage,shock,intestinal perforation and sepsis;the risk factors of poor prognosis of the early onset group of full-term NEC was shock;while those of the late onset group were shock and peritonitis;the risk factors of poor prognosis in the early onset group of preterm NEC were shock and sepsis,while those in the late onset group were pulmonary hemorrhage,shock,intestinal perforation and sepsis.Conclusions Compared to the preterm NEC,the onset time of full-term NEC was earlier and the clinical manifestations were more typical.Early identification and management of shock,peritonitis,intestinal perforation,sepsis and pulmonary hemorrhage can reduce the risk of poor prognosis of neonate NEC.
6.Role and related mechanism of S1P/S1P1 signal pathway during post conditioning of hypertrophic cardiomyocytes
Xinhui BAO ; Haixia LI ; Jing TAO ; Xiaomei LI ; Yining YANG ; Yitong MA ; Bangdang CHEN
Chinese Journal of Cardiology 2016;44(5):431-435
Objective To study the role and mechanism of sphingosine-l-phosphate (S1P)/sphingosine-1-phosphate receptor 1 (S1P1) signal pathway during post conditioning of hypertrophic cardiomyocytes.Methods Neonatal rat cardiomyocytes were isolated and cultured,then stimulated by norepinephrine (NE) to induce cardiomyocytes hypertrophy.Using tri-gas incubator to create hypoxia and reoxygenation enviroment to mimic ischemia-reperfusion and postconditioning.Hypertrophic cardiomyoctyes were divided into five groups according to the presence or absence of various drugs and postconditiong and relevant signal pathways changes were detected:(1) IPost group (hypoxia + postconditioning);(2) IPost + S1P group (cells were pretreated with S1P (1 μmol/L) for 2 h before IPost);(3) IPost + W-146 + S1P group (cells in IPost + W-146 + S1P group were pretreated with S1P1 inhibitor W-146 (0.4 μmol/L) for 20 min);(4) IPost + PD98059 + S1P group (cells in IPost + S1P group were pretreated with MAPK antagonist PD98059 (125 μmo[/L) for 20 min);(5) IPost + LY-294002 + S1P group (cells in IPost + S1P group were pretreated with PI3K antagonist LY294002 (0.1 μmol/L) for 20 min).Apoptosis was detected by flow cytometry and protein expression of relevant signal pathways were detected by Western blot.Results (1) Apoptosis rate was significantly increased in hypoxia/reoxygenation (27.90 ± 4.49) % group compared with normal control group (7.97 ± 2.18) %,which could be significantly reduced in IPost group (15.90 ± 1.77) % (all P < 0.05).(2) Apoptosis rate and caspase-3 expression were both significantly lower in IPost + S1P and IPost + S1P + LY-294002 groups than in IPost and IPost + S1P + W-146 and IPost + S1P + PD98059 group (all P < 0.05).(3)p-ERK1/2 expression was significantly higher in IPost + S1P and IPost + S1P + LY-294002 group than in IPost and IPost + SIP + W-146 group and IPost + S1P + PD98059 group (all P < 0.05) while p-Akt expression was similar among IPost,IPost + S1P + W-146 and IPost + S1P +PD98059 groups.p-ERK1/2 and p-Akt levels in IPost + S1P + W-146 group and IPost + S1P + PD98059 were similar as in IPost group.Conclusions S1P can play protective role on NE induced cardiomyocytes hypertrophy during post conditioning through downregulating caspase-3 expression and reducing apoptosis rate via targeting S1P1 and activating ERK1/2 signal pathway.

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