1.Mechanism of action of D-limonene on steatosis in primary hepatocytes based on AMPK/ACC/CPT1A signaling pathway
Qian-jun REN ; Su LI ; Yu-qing CHEN ; Yin-ying LIAO ; Chun-ni LIANG ; Rui-chao FANG ; Xu-dong LIU ; Xiao-fang ZHAO
Chinese Pharmacological Bulletin 2025;41(9):1665-1672
Aim To explore the effects of D-limonene on the steatosis of primary mouse hepatocytes and its potential mechanism of action.Methods Oleic acid-induced steatosis in primary mouse hepatocytes was used as a model to observe the effects of D-limonene on cell viability,cellular lipid content,and intracellular expression of proteins such as AMP-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase 1(ACC1),and carnitine palmitoyl transferase 1A(CPT1A).Results It was found that a low dose of D-limonene could effectively enhance the viability of primary mouse hepatocytes.When oleic acid at a con-centration of 300 μmol·L-1 successfully induced steatosis in primary mouse hepatocytes,D-limonene re-duced the lipid content of the cells,and D-limonene up-regulated the cellular AMPK expression level,down-regulated the cellular ACC1 and fatty acid synthetase(FAS)expression levels,which in turn promoted the overexpression of CPT1A.Conclusions D-limonene has the effect of reducing lipid deposition in primary mouse hepatocytes,and the mechanisms may be related to the activation of AMPK,the inhibitions of ACC1 and FAS,and the up-regulation of CPT1A protein expres-sion level.
2.Effects of Xuefu Zhuyu Decoction Combined with Cyproheptanidine Hydrochloride Tablets on Intracranial Arterial Hemodynamics,Oxygen Free Radicals and Vasoactive Factors in Patients with Migraine Caused by Blood Stasis Blocking Meridians
Xiao-li DONG ; Wei SUN ; Chun DING
Progress in Modern Biomedicine 2025;25(17):2783-2789
Objective:To explore the effects of Xuefu Zhuyu Decoction combine with Cyproheptanidine Hydrochloride Tablets on intracranial arterial hemodynamics,oxygen free radicals and vasoactive factors in patients with migraine caused by blood stasis blocking meridians.Methods:This study was a single-center prospective randomized controlled study,90 patients with migraine caused by blood stasis blocking meridians who were admitted to Zaozhuang Municipal Hospital Medical Group Canal Hospital from October 2022 to July 2024 were divided into control group(treated with Cyproheptanidine Hydrochloride Tablets,n=45)and study group(treated with Xuefu Zhuyu Decoction combined with Cyproheptanidine Hydrochloride Tablets,n=45)according to the random number table method.The TCM syndrome scores,visual analog scale(VAS),intracranial arterial hemodynamics[anterior cerebral artery(ACA),vertebral artery(VA),middle cerebral artery(MCA),basilar artery(BA)],serum oxygen free radicals[superoxide dismutase(SOD),malondialdehyde(MDA)],serum vasoactive factors[endothelin-1(ET-1),nitric oxide(NO)]between the two groups were compared.Results:The TCM syndrome scores,VAS score,MDA and ET-1 levels in the study group after treatment were lower than those in the control group,while ACA,MCA,VA and BA hemodynamics,and SOD and NO levels were higher than those in the control group(P<0.05).Conclusion:Xuefu Zhuyu Decoction combined with Cyproheptanidine Hydrochloride Tablets in the treatment of patients with migraine caused by blood stasis blocking meridians,can effectively improve intracranial arterial hemodynamics,control serum oxygen free radicals and vasoactive factors,and prevent the progression of the disease.
3.Mechanism of silibinin derivative Sil-1 modulating MAPK signaling pathway to inhibit acute myocardial infarction in rats
Yi-fan LIU ; Meng LI ; De-yu CUI ; Xiao-yan LU ; Ting-bo NING ; Chun-xiu XU ; Jing-chun YAO ; Ji-dong ZHOU ; Zhong LIU
Chinese Pharmacological Bulletin 2025;41(8):1453-1462
Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.
4.Effects of Xuefu Zhuyu Decoction Combined with Cyproheptanidine Hydrochloride Tablets on Intracranial Arterial Hemodynamics,Oxygen Free Radicals and Vasoactive Factors in Patients with Migraine Caused by Blood Stasis Blocking Meridians
Xiao-li DONG ; Wei SUN ; Chun DING
Progress in Modern Biomedicine 2025;25(17):2783-2789
Objective:To explore the effects of Xuefu Zhuyu Decoction combine with Cyproheptanidine Hydrochloride Tablets on intracranial arterial hemodynamics,oxygen free radicals and vasoactive factors in patients with migraine caused by blood stasis blocking meridians.Methods:This study was a single-center prospective randomized controlled study,90 patients with migraine caused by blood stasis blocking meridians who were admitted to Zaozhuang Municipal Hospital Medical Group Canal Hospital from October 2022 to July 2024 were divided into control group(treated with Cyproheptanidine Hydrochloride Tablets,n=45)and study group(treated with Xuefu Zhuyu Decoction combined with Cyproheptanidine Hydrochloride Tablets,n=45)according to the random number table method.The TCM syndrome scores,visual analog scale(VAS),intracranial arterial hemodynamics[anterior cerebral artery(ACA),vertebral artery(VA),middle cerebral artery(MCA),basilar artery(BA)],serum oxygen free radicals[superoxide dismutase(SOD),malondialdehyde(MDA)],serum vasoactive factors[endothelin-1(ET-1),nitric oxide(NO)]between the two groups were compared.Results:The TCM syndrome scores,VAS score,MDA and ET-1 levels in the study group after treatment were lower than those in the control group,while ACA,MCA,VA and BA hemodynamics,and SOD and NO levels were higher than those in the control group(P<0.05).Conclusion:Xuefu Zhuyu Decoction combined with Cyproheptanidine Hydrochloride Tablets in the treatment of patients with migraine caused by blood stasis blocking meridians,can effectively improve intracranial arterial hemodynamics,control serum oxygen free radicals and vasoactive factors,and prevent the progression of the disease.
5.Mechanism of silibinin derivative Sil-1 modulating MAPK signaling pathway to inhibit acute myocardial infarction in rats
Yi-fan LIU ; Meng LI ; De-yu CUI ; Xiao-yan LU ; Ting-bo NING ; Chun-xiu XU ; Jing-chun YAO ; Ji-dong ZHOU ; Zhong LIU
Chinese Pharmacological Bulletin 2025;41(8):1453-1462
Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.
6.Pharmacological actions of the bioactive compounds of Epimedium on the male reproductive system: current status and future perspective.
Song-Po LIU ; Yun-Fei LI ; Dan ZHANG ; Chun-Yang LI ; Xiao-Fang DAI ; Dong-Feng LAN ; Ji CAI ; He ZHOU ; Tao SONG ; Yan-Yu ZHAO ; Zhi-Xu HE ; Jun TAN ; Ji-Dong ZHANG
Asian Journal of Andrology 2025;27(1):20-29
Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male
;
Epimedium/chemistry*
;
Humans
;
Genitalia, Male/drug effects*
;
Flavonoids/therapeutic use*
;
Animals
7.Diagnosis of mucormycosis in three children following hematopoietic stem cell transplantation using metagenomic next-generation sequencing.
Yue LI ; Xiao-Hui ZHOU ; Xiao-Dong WANG ; Chun-Jing WANG ; Ke CAO ; Si-Xi LIU
Chinese Journal of Contemporary Pediatrics 2025;27(2):219-224
This article reports the clinical characteristics and treatment processes of three cases of mucormycosis occurring after hematopoietic stem cell transplantation in children, along with a review of relevant literature. All three patients presented with chest pain as the initial symptom, and metagenomic next-generation sequencing (mNGS) confirmed the mucycete infection early in all cases. Two patients recovered after treatment, while one succumbed to disseminated infection. mNGS has facilitated early diagnosis and treatment, reducing mortality rates. Additionally, surgical intervention is an important strategy for improving the prognosis of this condition.
Humans
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Hematopoietic Stem Cell Transplantation/adverse effects*
;
Mucormycosis/etiology*
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Male
;
High-Throughput Nucleotide Sequencing/methods*
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Child
;
Female
;
Metagenomics
;
Child, Preschool
8.Effect of Hesperidin on Chronic Unpredictable Mild Stress-Related Depression in Rats through Gut-Brain Axis Pathway.
Hui-Qing LIANG ; Shao-Dong CHEN ; Yu-Jie WANG ; Xiao-Ting ZHENG ; Yao-Yu LIU ; Zhen-Ying GUO ; Chun-Fang ZHANG ; Hong-Li ZHUANG ; Si-Jie CHENG ; Xiao-Hong GU
Chinese journal of integrative medicine 2025;31(10):908-917
OBJECTIVES:
To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis.
METHODS:
Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats.
RESULTS:
Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05).
CONCLUSION
The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals
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Hesperidin/therapeutic use*
;
Rats, Sprague-Dawley
;
Depression/drug therapy*
;
Male
;
Stress, Psychological/drug therapy*
;
Brain/metabolism*
;
Brain-Derived Neurotrophic Factor/metabolism*
;
Serotonin/metabolism*
;
Gastrointestinal Microbiome/drug effects*
;
Behavior, Animal/drug effects*
;
Rats
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Brain-Gut Axis/drug effects*
;
Chronic Disease
;
Colon/drug effects*
9.Glucocorticoid Discontinuation in Patients with Rheumatoid Arthritis under Background of Chinese Medicine: Challenges and Potentials Coexist.
Chuan-Hui YAO ; Chi ZHANG ; Meng-Ge SONG ; Cong-Min XIA ; Tian CHANG ; Xie-Li MA ; Wei-Xiang LIU ; Zi-Xia LIU ; Jia-Meng LIU ; Xiao-Po TANG ; Ying LIU ; Jian LIU ; Jiang-Yun PENG ; Dong-Yi HE ; Qing-Chun HUANG ; Ming-Li GAO ; Jian-Ping YU ; Wei LIU ; Jian-Yong ZHANG ; Yue-Lan ZHU ; Xiu-Juan HOU ; Hai-Dong WANG ; Yong-Fei FANG ; Yue WANG ; Yin SU ; Xin-Ping TIAN ; Ai-Ping LYU ; Xun GONG ; Quan JIANG
Chinese journal of integrative medicine 2025;31(7):581-589
OBJECTIVE:
To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM).
METHODS:
This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis.
RESULTS:
Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings.
CONCLUSIONS
RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult
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Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
Arthritis, Rheumatoid/drug therapy*
;
Glucocorticoids/therapeutic use*
;
Medicine, Chinese Traditional
;
Retrospective Studies
10.INVESTIGATION OF PATHOGENS CARRIED BY RODENTS AT YUNNAN HEKOU PORT
Xiao-Long ZHANG ; Dong WANG ; Jing ZHAO ; Zhi-Liang ZHAO ; Ling-Rui YUAN ; Run-Yi ZHOU ; Jie TIAN ; Hui-Lin GUO ; Chun-Yan GAO
Acta Parasitologica et Medica Entomologica Sinica 2025;32(1):27-33,51
Objective This research was performed to identify rodent-borne pathogens in Hekou Port,Yunnan Province.Methods Rodents were captured using cages and dissected to collect their lungs,liver,spleen,and other viscera.Eight pathogens,including Yersinia pestis,Leptospira,Bartonella,and Anaplasmataceae,were identified using polymerase chain reaction amplification.Amplified pathogen sequences from positive samples were sequenced,and BLAST homology searches were conducted using GenBank to confirm pathogen identities.A phylogenetic tree of the identified pathogens was constructed using the neighbor joining method.Results The total of 31 rodents,identified as Rattus tanezumi,R.norvegicus,and Mus musculus,were captured.Among these,R.tanezumi was the dominant species,accounting for 64.52%of the total.Two pathogens,Leptospira interrogans and Neoehrlichia mikurensis,were detected,with positivity rates of 9.68%and 29.03%,respectively.No other pathogens were detected.The overall positivity rate for rodent-borne pathogens was 35.48%.Conclusions The single 16S rRNA gene fragment is insufficient for the molecular identification of all Neoehrlichia species.Accurate species identification should be based on a combined analysis of multiple genes.The prevalence of rodent-borne pathogens in Hekou Port indicates the necessity for enhanced surveillance of rodent-borne diseases and implementation of additional prevention and control measures in border ports.

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