1.Effect of Zuogui Wan and Yougui Wan on Mitochondrial Biogenesis in BMSCs Through PGC-1α/PPARγ
Ying YANG ; Xiuzhi FENG ; Yiran CHEN ; Zhimin WANG ; Xian GUO ; Yanling REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):28-36
ObjectiveBased on the TCM theory of "Yang transforms materials to Qi while Yin constitutes material form", this paper explored the effects of Zuogui Wan and Yougui Wan on the molecular mechanism of mitochondrial biogenesis during the adipogenic differentiation process of rat bone marrow mesenchymal stem cells (BMSCs) by mediating peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and peroxisome proliferators-activated receptor γ (PPARγ), providing theoretical support for the prevention and treatment of postmenopausal osteoporosis (PMOP) using Zuogui Wan and Yougui Wan. MethodsBMSCs were divided into a blank group, Zuogui Wan (ZGW) group, Yougui Wan (YGW) group, and Progynova group. Cell identification was performed using flow cytometry. The growth curves of BMSCs were plotted using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) method, and the effects of Zuogui Wan and Yougui Wan on the proliferation of BMSCs were detected. The Oil red O staining method was used to detect lipid droplet formation. The Western blot method was used to detect the expression of adipogenesis-related factors PPARγ, CCAAT/enharcer-binding protein (C/EBP)α, C/EBPβ, lipoprotein lipase (LPL) protein, brown adipose tissue-related (BAT) proteins PGC-1α, uncoupcing protein 1 (UCP1), PR domdin-containing protein 16 (PRDM16), mitochondrial biogenesis-related PGC-1α, nuclear respiratory factor 1 (Nrf1), nuclear factor E2-related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). The expression of adipogenesis-related factors PPARγ, C/EBPα, C/EBPβ, LPL genes, and the copy number of cytochrome B (CytoB mtDNA) gene was detected using real-time polymerase chain reaction (Real-time PCR). Mitochondrial ultrastructure was detected using transmission electron microscopy. ResultsCompared with that in the blank group, the proliferation ability of BMSCs in each treatment group increased continuously as the intervention progressed, and lipid droplets significantly decreased after the drug intervention. The mRNA and protein expression levels of adipogenesis-related factors PPARγ, C/EBPα, C/EBPβ, and LPL were significantly downregulated (P<0.01), while those of the BAT-related factors PGC-1α, UCP1, PRDM16 were significantly upregulated (P<0.01). The number of mitochondria increased, accompanied by reduced swelling. The double membrane and cristae structure were clear, and the internal cristae rupture was reduced. The copy number of CytoB mtDNA in each treatment group was significantly increased (P<0.01). The protein expression levels of mitochondrial biogenesis-related PGC-1α, Nrf1, Nrf2, and TFAM in each treatment group were significantly increased (P<0.01). ConclusionBoth Zuogui Wan and Yougui Wan can prevent and treat PMOP by intervening in mitochondrial biogenesis in BMSCs through PGC-1α/PPARγ.
2.Research progress on strategies to target intestinal microbiota to improve drug resistance in tumor immunotherapy
Hui-ling LI ; Bi-qing LIU ; Ying-nan FENG ; Xin HU ; Lan ZHANG ; Xian-zhe DONG
Acta Pharmaceutica Sinica 2025;60(2):260-268
A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.
3.Diminished Compensatory Energy Production Following Hypoxic Stress in the Prefrontal and Anterior Cingulate Cortex Among Individuals With Schizophrenia
M Burak BAYTUNCA ; Xian-Feng SHI ; Nicolas A NUNẼZ ; Danielle BOXER ; Colleen FITZGERALD ; Dost ONGUR ; Deborah YURGELUN-TODD ; Perry RENSHAW ; Douglas KONDO
Psychiatry Investigation 2025;22(3):243-251
Objective:
The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls.
Methods:
Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans.
Results:
Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase.
Conclusion
These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.
4.Diminished Compensatory Energy Production Following Hypoxic Stress in the Prefrontal and Anterior Cingulate Cortex Among Individuals With Schizophrenia
M Burak BAYTUNCA ; Xian-Feng SHI ; Nicolas A NUNẼZ ; Danielle BOXER ; Colleen FITZGERALD ; Dost ONGUR ; Deborah YURGELUN-TODD ; Perry RENSHAW ; Douglas KONDO
Psychiatry Investigation 2025;22(3):243-251
Objective:
The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls.
Methods:
Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans.
Results:
Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase.
Conclusion
These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.
5.Diminished Compensatory Energy Production Following Hypoxic Stress in the Prefrontal and Anterior Cingulate Cortex Among Individuals With Schizophrenia
M Burak BAYTUNCA ; Xian-Feng SHI ; Nicolas A NUNẼZ ; Danielle BOXER ; Colleen FITZGERALD ; Dost ONGUR ; Deborah YURGELUN-TODD ; Perry RENSHAW ; Douglas KONDO
Psychiatry Investigation 2025;22(3):243-251
Objective:
The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls.
Methods:
Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans.
Results:
Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase.
Conclusion
These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.
6.Diminished Compensatory Energy Production Following Hypoxic Stress in the Prefrontal and Anterior Cingulate Cortex Among Individuals With Schizophrenia
M Burak BAYTUNCA ; Xian-Feng SHI ; Nicolas A NUNẼZ ; Danielle BOXER ; Colleen FITZGERALD ; Dost ONGUR ; Deborah YURGELUN-TODD ; Perry RENSHAW ; Douglas KONDO
Psychiatry Investigation 2025;22(3):243-251
Objective:
The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls.
Methods:
Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans.
Results:
Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase.
Conclusion
These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.
7.Diminished Compensatory Energy Production Following Hypoxic Stress in the Prefrontal and Anterior Cingulate Cortex Among Individuals With Schizophrenia
M Burak BAYTUNCA ; Xian-Feng SHI ; Nicolas A NUNẼZ ; Danielle BOXER ; Colleen FITZGERALD ; Dost ONGUR ; Deborah YURGELUN-TODD ; Perry RENSHAW ; Douglas KONDO
Psychiatry Investigation 2025;22(3):243-251
Objective:
The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls.
Methods:
Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans.
Results:
Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase.
Conclusion
These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.
8.The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.
Xiaoxuan ZHONG ; Xiang WEI ; Yan XU ; Xuehai ZHU ; Bo HUO ; Xian GUO ; Gaoke FENG ; Zihao ZHANG ; Xin FENG ; Zemin FANG ; Yuxuan LUO ; Xin YI ; Ding-Sheng JIANG
Acta Pharmaceutica Sinica B 2024;14(2):712-728
Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.
9.Preliminary construction of a measurement tool for atrial fibrillation patient's experience of catheter ablation
Ming-Li DU ; Song-Wen CHEN ; Li ZHU ; Xian-Feng YAO ; Lei YE ; Shao-Wen LIU
Fudan University Journal of Medical Sciences 2024;51(2):198-204
Objective To construct a measurement tool for atrial fibrillation(AF)patients'experience of catheter ablation,in order to provide quantifiable basis for improving the patients'perioperative experience.Methods From Jun 2022 to Apr 2023,literature analysis,qualitative research,Delphi expert consultation,and analytic hierarchy process were used to determine the content and weight of various indicators of the measurement tool.Results The enthusiasm of experts in 3 rounds was 100%.The authority coefficient of experts was 0.946,0.961 and 0.976.The Kendal harmony coefficients of the 2 and 3 rounds of expert consultation was 0.130 and 0.370(P<0.001).The final measurement tool included 46 items and 5 dimensions,including operational and technical quality experience,comfort management experience,information and communication experience,emotional support experience,service process and response experience.Conclusion The preliminary construction of measurement tool for AF patients'experience of catheter ablation,which were based on the features of specialty,could not only evaluate the patients'experience accurately,but also provide a basis for targeted improvement of medical and nursing service quality.
10.Relationship between drainage time and early efficacy after short-segment lumbar fusion
Zan CHEN ; Fei LEI ; Fei YE ; Qingzhong ZHOU ; Hao YUAN ; Lipeng ZHENG ; Xian ZHA ; Daxiong FENG
Chinese Journal of Tissue Engineering Research 2024;28(6):927-933
BACKGROUND:As a routine method after lumbar spine surgery,a drainage tube is convenient for postoperative bleeding drainage and management,and there is still no consensus on the choice of postoperative removal time for short-segment lumbar spine surgery with less risk. OBJECTIVE:To explore the effect of different drainage times on early clinical efficacy after short-segment lumbar fusion. METHODS:A prospective randomized controlled study was performed on 220 patients in the Affiliated Hospital of Southwest Medical University who underwent posterior lumbar interbody fusion for lumbar degenerative diseases from March 2017 to April 2021.According to the different drainage times,the patients were randomly divided into removal on the second day after operation(group A),removal on the third day after operation(group B),and removal after the observation method 24-hour drainage volume<30 mL(group C).The perioperative indicators and follow-up results of the three groups of patients were observed and compared. RESULTS AND CONCLUSION:(1)Because 7 patients were lost to follow-up,2 patients were excluded,and 211 patients were finally included(72 patients in group A,71 patients in group B,and 68 patients in group C).(2)The average drainage time of group C was 2.91 days.The postoperative drainage volume in group A was significantly less than that in groups B and C,and the difference was statistically significant(P<0.05).On day 3 after operation,the hematocrit value of group C was lower than that of group A and group B,and the difference was statistically significant(P<0.05).Postoperative activity time and hospital stay in group A were shorter than those in groups B and C,and the difference was statistically significant(P<0.05).(3)Four patients in group A,two patients in group B and three patients in group C received an allogeneic blood transfusion.There was no significant difference among the groups(P>0.05).(4)In terms of postoperative complications,there were no statistical differences in postoperative wound leakage and surgical site infection in all three groups(P>0.05).(5)All patients were followed up for more than 12 months.Visual analog scale score and Oswestry dysfunction index of the three groups of patients before discharge and at the last follow-up were significantly improved compared with those before surgery(P<0.05).There was no statistical significance among the groups(P>0.05).(6)It is indicated that the removal of the drainage tube on the second day after a posterior lumbar fusion can effectively reduce the time to get out of bed and hospital stay,without increasing the postoperative blood loss and the risk of complications.

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