1.Research progress on NCOA4-mediated ferritinophagy and related diseases.
Chen JIA ; Hong-Ji LIN ; Fang CUI ; Rui LU ; Yi-Ting ZHANG ; Zhi-Qin PENG ; Min SHI
Acta Physiologica Sinica 2025;77(1):194-208
Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans
;
Nuclear Receptor Coactivators/physiology*
;
Ferritins/metabolism*
;
Animals
;
Neurodegenerative Diseases/metabolism*
;
Iron/metabolism*
;
Autophagy/physiology*
;
Liver Cirrhosis/metabolism*
;
Carcinoma, Renal Cell/metabolism*
;
Kidney Neoplasms/physiopathology*
2.Advances in the function and mechanisms of stearoyl-CoA desaturase 1 in metabolic diseases.
Qin SUN ; Xiao-Rui XING ; Cheng LIU ; Dan-Dan JIA ; Ru WANG
Acta Physiologica Sinica 2025;77(3):545-562
Metabolic diseases characterized by an imbalance in energy homeostasis represent a significant global health challenge. Individuals with metabolic diseases often suffer from complications related to disorders in lipid metabolism, such as obesity and non-alcoholic fatty liver disease (NAFLD). Understanding core genes involved in lipid metabolism can advance strategies for the prevention and treatment of these conditions. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in lipid metabolism that converts saturated fatty acids into monounsaturated fatty acids. SCD1 plays a crucial regulatory role in numerous physiological and pathological processes, including energy homeostasis, glycolipid metabolism, autophagy, and inflammation. Abnormal transcription and epigenetic activation of Scd1 contribute to abnormal lipid accumulation by regulating multiple signaling axes, thereby promoting the development of obesity, NAFLD, diabetes, and cancer. This review comprehensively summarizes the key role of SCD1 as a metabolic hub gene in various (patho)physiological contexts. Further it explores potential translational avenues, focusing on the development of novel SCD1 inhibitors across interdisciplinary fields, aiming to provide new insights and approaches for targeting SCD1 in the prevention and treatment of metabolic diseases.
Stearoyl-CoA Desaturase/metabolism*
;
Humans
;
Metabolic Diseases/physiopathology*
;
Lipid Metabolism/physiology*
;
Animals
;
Obesity/enzymology*
;
Non-alcoholic Fatty Liver Disease
3.Preparation, characterization, and in vitro anti-liver tumor activity of bufalin nanoparticles with Scrophularia ningpoensis polysaccharide and ursodeoxycholic acid as carriers.
Zhen ZHENG ; Bi-Qi DENG ; Xue-Mei CHEN ; Li-Qiao ZHU ; Hua-Gang SHENG
China Journal of Chinese Materia Medica 2025;50(11):3013-3023
Bufalin(BF)has a significant anti-tumor effect, but its clinical application is severely restricted by its high toxicity and poor water solubility. In this study, Scrophularia ningpoensis polysaccharide(SNP)and ursodeoxycholic acid(UDCA) were synthesized into an SNP-UDCA conjugate. BF was encapsulated to prepare BF/SNP-UDCA nanoparticles(NPs). The amphiphilic compound SNP-UDCA was synthesized via the one-step method, and its structure was characterized by Fourier-transform infrared spectroscopy(FT-IR)and proton nuclear magnetic resonance(~1H-NMR). The preparation process of BF/SNP-UDCA NPs was optimized through single-factor investigations. The encapsulation efficiency and drug-loading capacity of BF/SNP-UDCA NPs were determined by high-performance liquid chromatography(HPLC). The molecular form of BF/SNP-UDCA NPs was characterized by using a transmission electron microscope, X-ray diffraction(XRD), and differential scanning calorimeter(DSC). Additionally, the stability of BF/SNP-UDCA NPs was evaluated. The release behavior of BF/SNP-UDCA NPs at different pH values was determined by dialysis. The in vitro anti-tumor effect of BF/SNP-UDCA NPs was evaluated by MTT cytotoxicity assay, flow cytometry for apoptosis, and cellular uptake. The in vitro liver targeting was evaluated by measuring cellular uptake by laser confocal microscopy. The results demonstrated that the SNP-UDCA conjugate was successfully synthesized through an esterification reaction between SNP and UDCA. The preparation process of BF/SNP-UDCA NPs was as follows: the feed ratio of SNP-UDCA to BF was 2∶1, the ultrasonic time was 30 minutes, and the stirring time was two hours. The prepared BF/SNP-UDCA NPs were spherical in shape, with a particle size of(252.74±6.05)nm, an encapsulation efficiency of 65.00%±2.51%, and a drug-loading capacity of 6.80%±0.44%. The XRD and DSC results indicated that BF was encapsulated within the NPs and existed in a molecular or amorphous state. The short-term stability of BF/SNP-UDCA NPs and stability in DMEM medium are good, and their in vitro release behavior followed the first-order equation and was pH-dependent according to the in vitro experiment. Compared with BF, BF/SNP-UDCA NPs at the same concentration showed significantly stronger cytotoxicity and apoptotic effects on HepG2 cells(P<0.05, P<0.01). The uptake of coumarin 6(C6)/SNP-UDCA NPs in HepG2 cells was time-dependent and higher than that in HeLa cells at the same concentration of C6/SNP-UDCA NPs. Moreover, after treatment with SNP, the uptake of C6/SNP-UDCA NPs in HepG2 cells decreased. In conclusion, the preparation process of BF/SNP-UDCA NPs was simple and feasible. BF/SNP-UDCA NPs could enhance the targeting ability and inhibitory effect of BF on liver cancer cells. This study will provide a foundation for liver-targeting nanoformulations of BF.
Bufanolides/pharmacology*
;
Nanoparticles/chemistry*
;
Humans
;
Drug Carriers/chemistry*
;
Ursodeoxycholic Acid/chemistry*
;
Antineoplastic Agents/pharmacology*
;
Polysaccharides/chemistry*
;
Scrophularia/chemistry*
;
Liver Neoplasms/physiopathology*
;
Hep G2 Cells
4.Glycyrrhetinic acid combined with doxorubicin induces apoptosis of human hepatocellular carcinoma HepG2 cells by regulating ERMMDs.
Ming-Shi PANG ; Xiu-Yun BAI ; Jue YANG ; Rong-Jun DENG ; Xue-Qin YANG ; Yuan-Yan LIU
China Journal of Chinese Materia Medica 2025;50(11):3088-3096
This study investigates the effect of glycyrrhetinic acid(GA) combined with doxorubicin(DOX) on apoptosis in HepG2 cells and its possible mechanisms. HepG2 cells were cultured in vitro, and cell viability was assessed using the cell counting kit-8(CCK-8) method. Flow cytometry was used to measure apoptosis levels in HepG2 cells. The cells were divided into the following groups: control group(0 μmol·L~(-1)), DOX group(2 μmol·L~(-1)), GA group(150 μmol·L~(-1)), and DOX + GA combination group(2 μmol·L~(-1) DOX + 150 μmol·L~(-1) GA), with treatments given for 24 hours. The colocalization level between the endoplasmic reticulum(ER) and mitochondria was assessed by colocalization fluorescence imaging. Fluorescence probes were used to measure the Ca~(2+) content in the ER and mitochondria. The qRT-PCR and Western blot were used to determine the mRNA and protein expression of sirtuin-3(SIRT3). Co-immunoprecipitation(CO-IP) was applied to investigate the interactions between voltage-dependent anion channel 1(VDAC1) and SIRT3, as well as between VDAC1, glucose-regulated protein 75(GRP75), and inositol 1,4,5-trisphosphate receptor(IP3R). The results showed that the combination of DOX and GA promoted apoptosis in HepG2 liver cancer cells. The colocalization level between the ER and mitochondria was significantly reduced, the Ca~(2+) content in the ER was significantly increased, and the Ca~(2+) content in the mitochondria was significantly decreased. The relative expression of VDAC1, GRP75, and IP3R was significantly reduced, and interactions between VDAC1, GRP75, and IP3R were observed. SIRT3 mRNA and protein expression levels were significantly increased, and an interaction between SIRT3 and VDAC1 was detected. The acetylation level of VDAC1 was significantly decreased. In conclusion, GA combined with DOX induces apoptosis in HepG2 cells by mediating the deacetylation of VDAC1 through SIRT3, weakening the interactions among VDAC1, GRP75, and IP3R. This regulates the formation of endoplasmic reticulum-mitochondrial membrane domains(ERMMDs), affects Ca~(2+) transport between the ER and mitochondria, and ultimately triggers cell apoptosis.
Humans
;
Apoptosis/drug effects*
;
Hep G2 Cells
;
Glycyrrhetinic Acid/pharmacology*
;
Doxorubicin/pharmacology*
;
Liver Neoplasms/genetics*
;
Carcinoma, Hepatocellular/physiopathology*
;
Mitochondria/metabolism*
;
Endoplasmic Reticulum/metabolism*
;
Cell Survival/drug effects*
;
Membrane Proteins/genetics*
5.Relevance of intra-abdominal pressure monitoring in non-operative management of patients with blunt liver and splenic injuries.
Vivek KUMAR ; Ramesh VAIDYANATHAN ; Dinesh BAGARIA ; Pratyusha PRIYADARSHINI ; Abhinav KUMAR ; Narendra CHOUDHARY ; Sushma SAGAR ; Amit GUPTA ; Biplab MISHRA ; Mohit JOSHI ; Kapil Dev SONI ; Richa AGGARWAL ; Subodh KUMAR
Chinese Journal of Traumatology 2025;28(4):307-312
PURPOSE:
Non-operative management (NOM) has been validated for blunt liver and splenic injuries. Literature on continuous intra-abdominal pressure (IAP) monitoring as a part of NOM remains to be equivocal. The study aimed to find any correlation between clinical parameters and IAP, and their effect on the NOM of patients with blunt liver and splenic injury.
METHOD:
A prospective cross-sectional study conducted at a level I trauma center from October 2018 to January 2020 including 174 patients who underwent NOM following blunt liver and splenic injuries. Hemodynamically unstable patients or those on ventilators were excluded, as well as patients who suffered significant head, spinal cord, and/or bladder injuries. The study predominantly included males (83.9%) with a mean age of 32.5 years. IAP was monitored continuously and the relation of IAP with various parameters, interventions, and outcomes were measured. Data were summarized as frequency (percentage) or mean ± SD or median (Q1, Q3) as indicated. χ2 or Fisher's exact test was used for categorical variables, while for continuous variables parametric (independent t-test) or nonparametric tests (Wilcoxon rank sum test) were used as appropriate. Clinical and laboratory correlates of IAP < 12 with p < 0.200 in the univariable logistic regression analysis were included in the multivariable analysis. A p < 0.05 was used to indicate statistical significance.
RESULTS:
Intra-abdominal hypertension (IAH) was seen in 19.0% of the study population. IAH was strongly associated with a high injury severity score (p < 0.001), and other physiological parameters like respiratory rate (p < 0.001), change in abdominal girth (AG) (p < 0.001), and serum creatinine (p < 0.001). IAH along with the number of solid organs involved, respiratory rate, change in AG, and serum creatinine was associated with the intervention, either operative or non-operative (p = 0.001, p = 0.002, p < 0.001, p < 0.001, p = 0.013, respectively). On multivariable analysis, IAP (p = 0.006) and the mean change of AG (p = 0.004) were significantly associated with the need for intervention.
CONCLUSION
As a part of NOM, IAP should be monitored as a continuous vital. However, the decision for any intervention, either operative or non-operative cannot be guided by IAP values alone.
Humans
;
Male
;
Adult
;
Female
;
Wounds, Nonpenetrating/physiopathology*
;
Spleen/injuries*
;
Prospective Studies
;
Cross-Sectional Studies
;
Liver/injuries*
;
Middle Aged
;
Monitoring, Physiologic/methods*
;
Pressure
;
Abdominal Injuries/physiopathology*
;
Intra-Abdominal Hypertension
;
Young Adult
6.Early liver injury risk assessment in critically injured trauma patients using intelligent calculation method: a retrospective study.
Xiaoming HOU ; Wenjun ZHAO ; Wenhua LI ; Xiaomei WANG ; Baoqi ZENG ; Xiaozhi LIU ; Qingguo FENG ; Bo KANG ; Na XUE
Chinese Critical Care Medicine 2025;37(2):165-169
OBJECTIVE:
To explore the early changes in various liver function indicators in critically injured trauma patients assessed by intelligent calculation method, aiming to develop more advantageous diagnostic and treatment strategies for traumatic liver injury.
METHODS:
A retrospective study was conducted. Critically injured trauma patients [injury severity score (ISS) ≥ 16, age > 18 years old] admitted to the Emergency Medical Center of Tianjin Fifth Central Hospital from January 1, 2022, to December 1, 2023 were enrolled. ISS score and acute physiology and chronic health evaluation II (APACHE II) assessed by intelligent calculation method were collected upon patient admission to the emergency medical center. Trends in liver function indicators in fasting venous serum were analyzed at 6, 24 and 72 hours after admission, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), albumin (ALB), total bilirubin (TBil), prothrombin time (PT). Patients were grouped based on APACHE II scores into those with APACHE II < 15 and APACHE II ≤ 15, and liver function indicators within 6 hours of admission were compared between the two groups.
RESULTS:
A total of 112 critically injured trauma patients were included, with 83 males and 29 females, an average age of (47.78±14.84) years old. The median ISS score was 21.0 (18.0, 26.0). The most common cause of injury for critically injured trauma patients was road traffic accidents (68 cases, accounting for 60.71%), followed by falls from heights, compression injuries, heavy object injuries, knife stabs, and explosion injuries. The most common injured areas was the limbs and pelvis (97 cases, accounting for 86.61%), followed by chest injuries, surface skin and soft tissue injuries, abdominal and pelvic organ injuries, head injuries, and facial injuries. The proportion of elevated LDH, AST, and ALT within 6 hours of admission was 77.68%, 79.46%, and 52.68%, respectively, while the proportion of decreased ALB was 75.89%, the abnormal rates of ALP, GGT, TBil, and PT were all below 50%. The ALT and AST levels of patients at 24 hours and 72 hours after admission were significantly lower than those at 6 hours after admission [ALT (U/L): 37.0 (22.0, 66.0), 31.0 (21.2, 52.0) vs. 41.0 (25.0, 71.0), AST (U/L): 55.5 (30.0, 93.5), 40.0 (27.0, 63.2) vs. 69.5 (39.0, 130.8), all P < 0.05]. There was no statistically significant difference in ISS score between APACHE II > 15 group (45 cases) and APACHE II ≤ 15 group [67 cases; 21.0 (18.5, 26.5) vs. 20.0 (17.0, 22.0), P > 0.05]. Nevertheless, compared with patients with APACHE II ≤ 15, patients with APACHE II > 15 have a higher abnormality rate of ALT and AST within 6 hours of admission [ALT abnormal rate: 66.44% (29/45) vs. 44.78% (30/67), AST abnormal rate: 93.33% (42/45) vs. 70.15% (47/67), both P < 0.05], and the levels of ALT and AST were higher [ALT (U/L): 56.0 (30.0, 121.0) vs. 35.0 (21.0, 69.0), AST (U/L): 87.0 (48.0, 233.0) vs. 52.0 (31.0, 117.0), both P < 0.05].
CONCLUSIONS
Severe trauma patients frequently exhibit a high incidence of reversible early liver function impairment. Based on intelligent calculation method, the utilization of both the ISS and APACHE II scores demonstrates a distinct advantage in the assessment of their early liver injury.
Humans
;
Retrospective Studies
;
Liver/physiopathology*
;
Risk Assessment
;
APACHE
;
Wounds and Injuries
;
Adult
;
Injury Severity Score
;
Male
;
Middle Aged
;
Female
;
Liver Function Tests
;
Alanine Transaminase/blood*
;
Young Adult
;
Aspartate Aminotransferases/blood*
7.A machine learning model for predicting abnormal liver function induced by a Chinese herbal medicine preparation (Zhengqing Fengtongning) in patients with rheumatoid arthritis based on real-world study.
Ze YU ; Fang KOU ; Ya GAO ; Fei GAO ; Chun-Ming LYU ; Hai WEI
Journal of Integrative Medicine 2025;23(1):25-35
OBJECTIVE:
Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients' quality of life. Zhengqing Fengtongning (ZF) is a traditional Chinese medicine preparation used to treat RA. ZF may cause liver injury. In this study, we aimed to develop a prediction model for abnormal liver function caused by ZF.
METHODS:
This retrospective study collected data from multiple centers from January 2018 to April 2023. Abnormal liver function was set as the target variable according to the alanine transaminase (ALT) level. Features were screened through univariate analysis and sequential forward selection for modeling. Ten machine learning and deep learning models were compared to find the model that most effectively predicted liver function from the available data.
RESULTS:
This study included 1,913 eligible patients. The LightGBM model exhibited the best performance (accuracy = 0.96) out of the 10 learning models. The predictive metrics of the LightGBM model were as follows: precision = 0.99, recall rate = 0.97, F1_score = 0.98, area under the curve (AUC) = 0.98, sensitivity = 0.97 and specificity = 0.85 for predicting ALT < 40 U/L; precision = 0.60, recall rate = 0.83, F1_score = 0.70, AUC = 0.98, sensitivity = 0.83 and specificity = 0.97 for predicting 40 ≤ ALT < 80 U/L; and precision = 0.83, recall rate = 0.63, F1_score = 0.71, AUC = 0.97, sensitivity = 0.63 and specificity = 1.00 for predicting ALT ≥ 80 U/L. ZF-induced abnormal liver function was found to be associated with high total cholesterol and triglyceride levels, the combination of TNF-α inhibitors, JAK inhibitors, methotrexate + nonsteroidal anti-inflammatory drugs, leflunomide, smoking, older age, and females in middle-age (45-65 years old).
CONCLUSION
This study developed a model for predicting ZF-induced abnormal liver function, which may help improve the safety of integrated administration of ZF and Western medicine. Please cite this article as: Yu Z, Kou F, Gao Y, Lyu CM, Gao F, Wei H. A machine learning model for predicting abnormal liver function induced by a Chinese herbal medicine preparation (Zhengqing Fengtongning) in patients with rheumatoid arthritis based on real-world study. J Integr Med. 2025; 23(1): 25-35.
Humans
;
Arthritis, Rheumatoid/drug therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Female
;
Middle Aged
;
Male
;
Retrospective Studies
;
Machine Learning
;
Adult
;
Aged
;
Liver/physiopathology*
;
Alanine Transaminase/blood*
8.Esculetin triggers ferroptosis via inhibition of the Nrf2-xCT/GPx4 axis in hepatocellular carcinoma.
Zhixin QU ; Jing ZENG ; Laifeng ZENG ; Xianmei LI ; Fenghua ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(4):443-456
Esculetin, a natural dihydroxy coumarin derived from the Chinese herbal medicine Cortex Fraxini, has demonstrated significant pharmacological activities, including anticancer properties. Ferroptosis, an iron-dependent form of regulated cell death, has garnered considerable attention due to its lethal effect on tumor cells. However, the exact role of ferroptosis in esculetin-mediated anti-hepatocellular carcinoma (HCC) effects remains poorly understood. This study investigated the impact of esculetin on HCC cells both in vitro and in vivo. The findings indicate that esculetin effectively inhibited the growth of HCC cells. Importantly, esculetin promoted the accumulation of intracellular Fe2+, leading to an increase in ROS production through the Fenton reaction. This event subsequently induced lipid peroxidation (LPO) and triggered ferroptosis within the HCC cells. The occurrence of ferroptosis was confirmed by the elevation of malondialdehyde (MDA) levels, the depletion of glutathione peroxidase (GSH-Px) activity, and the disruption of mitochondrial morphology. Notably, the inhibitor of ferroptosis, ferrostatin-1 (Fer-1), attenuated the anti-tumor effect of esculetin in HCC cells. Furthermore, the findings revealed that esculetin inhibited the Nrf2-xCT/GPx4 axis signaling in HCC cells. Overexpression of Nrf2 upregulated the expression of downstream SLC7A11 and GPX4, consequently alleviating esculetin-induced ferroptosis. In conclusion, this study suggests that esculetin exerts an anti-HCC effect by inhibiting the activity of the Nrf2-xCT/GPx4 axis, thereby triggering ferroptosis in HCC cells. These findings may contribute to the potential clinical use of esculetin as a candidate for HCC treatment.
Umbelliferones/administration & dosage*
;
Ferroptosis/drug effects*
;
Carcinoma, Hepatocellular/physiopathology*
;
NF-E2-Related Factor 2/genetics*
;
Humans
;
Liver Neoplasms/physiopathology*
;
Phospholipid Hydroperoxide Glutathione Peroxidase/genetics*
;
Animals
;
Cell Line, Tumor
;
Mice
;
Amino Acid Transport System y+/genetics*
;
Mice, Inbred BALB C
;
Male
;
Signal Transduction/drug effects*
;
Lipid Peroxidation/drug effects*
;
Reactive Oxygen Species/metabolism*
;
Mice, Nude
9.Electroacupuncture at acupoints of liver meridian for diminished ovarian reserve of liver depression: a randomized controlled trial.
Qiuping LUO ; Zhihong YANG ; Lingmin JIN ; Panbi CHEN ; Yun JIANG ; Qingke LI ; Wei ZHANG ; Xiaofang YANG
Chinese Acupuncture & Moxibustion 2024;44(11):1261-1266
OBJECTIVE:
To observe the therapeutic effect of electroacupuncture at acupoints of liver meridian in patients with diminished ovarian reserve (DOR) of liver depression.
METHODS:
A total of 62 patients with DOR of liver depression were randomly divided into an electroacupuncture group (31 cases, 1 case discontinued) and a western medication group (31 cases, 1 case was eliminated). Electroacupuncture was applied at bilateral Taichong (LR 3), Ligou (LR 5), Ququan (LR 8), Jimai (LR 12) in the electroacupuncture group, with continuous wave, in frequency of 2 Hz and current of 0.5-1.0 mA, 30 min each time, once every other day, 3 times a week. Femoston was taken orally in the western medication group, oral estradiol tablets were taken for the first 14 days, followed by oral estradiol/progesterone complex tablets for the rest 14 days, 1 tablet a day. Both groups were treated for 3 consecutive menstrual cycles. Before and after treatment, the scores of TCM syndrome, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed, serum levels of follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) were detected, and antral follicle count (AFC), peak systolic velocity (PSV) and resistance index (RI) of ovarian artery were measured by color Doppler ultrasound in the two groups, and the clinical efficacy was evaluated after treatment.
RESULTS:
After treatment, the scores of primary symptom and secondary symptom, as well as the total scores of TCM syndrome were decreased compared with those before treatment (P<0.01), the scores of SAS and SDS, as well as the serum FSH levels and RI of ovarian artery were decreased compared with those before treatment (P<0.01), while the serum AMH levels, AFC and PSV of ovarian artery were increased compared with those before treatment (P<0.05, P<0.01) in the two groups. After treatment, in the electroacupuncture group, the primary symptom score of TCM syndrome was higher than that in the western medication group (P<0.01), the secondary symptom score of TCM syndrome and the scores of SAS and SDS were lower than those in the western medication group (P<0.05, P<0.01). The total effective rate was 70.0% (21/30) in the electroacupuncture group and 73.3% (22/30) in the western medication group respectively, there was no significant difference in the total effective rate between the two groups (P>0.05).
CONCLUSION
Electroacupuncture at acupoints of liver meridian can effectively improve the clinical symptoms, anxiety and depression, regulate the serum sex hormone levels, increase AFC and improve ovarian blood supply in DOR patients of liver depression.
Humans
;
Female
;
Electroacupuncture
;
Adult
;
Acupuncture Points
;
Meridians
;
Ovarian Reserve
;
Young Adult
;
Liver Diseases/physiopathology*
;
Liver/metabolism*
;
Ovary/physiopathology*
;
Treatment Outcome
;
Depression/therapy*
10.Effects of interleukin-17A on liver and kidney injury and prognosis in septic mice.
Yonghui LIANG ; Chun GUAN ; Haining MENG ; Weifeng XIE ; Xiangqi MENG ; Yan QU
Chinese Critical Care Medicine 2023;35(6):592-597
OBJECTIVE:
To explore the effect of interleukin-17A (IL-17A) on liver and kidney injury and prognosis in septic mice.
METHODS:
A total of 84 SPF male C57BL/6 mice were randomly divided into sham operation group (Sham group), cecal ligation and puncture (CLP) induced sepsis model group (CLP group), and IL-17A intervention group. IL-17A intervention group were then divided into five subgroups according to the dose of IL-17A (0.25, 0.5, 1, 2, 4 μg). Mice in the IL-17A intervention group were intraperitoneally injected with the corresponding dose of IL-17A 100 μL immediately after surgery. The other groups were intraperitoneally injected with 100 μL phosphate buffer solution (PBS). The survival rate of mice was observed at 7 days, and peripheral blood and liver, kidney and spleen tissues were collected. According to the 7-day survival, another 18 mice were randomly divided into Sham group, CLP group, and 1 μg IL-17A intervention group. Peripheral blood samples were collected at 12 hours and 24 hours after CLP, and the mice were sacrificed to obtain liver, kidney, and spleen tissues. The behavior and abdominal cavity of each group were observed. The levels of peripheral blood liver and kidney function indexes and inflammatory factors were detected. The histopathological changes of liver and kidney were observed under light microscope. The peripheral blood and spleen tissues were inoculated in the medium, the number of bacterial colonies was calculated, and the bacterial migration of each group was evaluated in vitro.
RESULTS:
Except for the Sham group, the 7-day survival rate of mice in the 1 μg IL-17A intervention group was the highest (75.0%), so this condition was selected as the intervention condition for the subsequent study. Compared with Sham group, the liver and kidney functions of CLP group were significantly damaged at each time point after operation. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and serum creatinine (SCr) reached the peak at 24 hours after operation, and the liver and kidney pathological scores reached the peak at 7 days after operation, the levels of inflammatory cytokines interleukin (IL-17A, IL-6, IL-10) reached the peak at 12 hours after operation, and tumor necrosis factor-α (TNF-α) reached the peak at 24 hours after operation. In addition, a large number of bacteria proliferated in the peripheral blood and spleen, which reached the peak on day 7. Compared with the CLP group, exogenous administration of 1 μg IL-17A significantly delayed the rising trend of each index in the early stage of sepsis [24-hour ALT (U/L): 166.95±5.20 vs. 271.30±6.11, 24-hour AST (U/L): 599.42±7.25 vs. 1 013.27±3.37, 24-hour BUN (mg/L): 815.4±26.3 vs. 1 191.2±39.4, 24-hour SCr (μmol/L): 29.34±0.87 vs. 60.75±3.83, 7-day liver pathological score: 2.50 (2.00, 3.00) vs. 9.00 (8.50, 9.00), 7-day kidney pathological score: 1.00 (1.00, 2.00) vs. 5.00 (4.50, 5.00), 12-hour IL-17A (ng/L): 105.21±0.31 vs. 111.28±1.37, 12-hour IL-6 (ng/L): 83.22±1.01 vs. 108.88±0.99, 12-hour IL-10 (ng/L): 731.54±3.04 vs. 790.25±2.54, 24-hour TNF-α (μg/L): 454.67±0.66 vs. 576.18±0.76, 7-day peripheral blood colony count (CFU/mL): 600 (400, 600) vs. 4 200 (4 200, 4 300), 7-day spleen tissue colony count (CFU/g): 4 600 (4 400, 4 600) vs. 23 400 (23 200, 23 500), all P < 0.05].
CONCLUSIONS
Appropriate dose (1 μg) of exogenous IL-17A can reduce the lethal inflammatory response induced by CLP and improve the ability of bacterial clearance, thereby alleviating liver and kidney injury and improving the 7-day survival rate of septic mice.
Animals
;
Male
;
Mice
;
Interleukin-10
;
Interleukin-17/pharmacology*
;
Interleukin-6
;
Kidney/physiopathology*
;
Liver/physiopathology*
;
Mice, Inbred C57BL
;
Prognosis
;
Sepsis
;
Tumor Necrosis Factor-alpha

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