OBJECTIVE: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization. METHODS: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells. RESULTS: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4. CONCLUSION SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; 22(6): 666-683.
Ferroptosis/drug effects* ; Female ; Humans ; Animals ; Scutellaria/chemistry* ; Ovarian Neoplasms/genetics* ; Zebrafish ; Cell Line, Tumor ; Ferritins/genetics* ; Plant Extracts/pharmacology* ; Heme/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Autophagy/drug effects* ; Apoptosis/drug effects*

Objective: To evaluate the short-and mid-term efficacy of pediatric kidney transplantation and the risk factors for kidney graft and recipient. Methods: The baseline data and postoperative complications of pediatric donors and recipients of 284 kidney transplants were retrospectively analyzed in the Department of Kidney Transplantation in the First Affiliated Hospital of Zhengzhou University from August 2010 to May 2021 and all subjects were followed up until December 31, 2021. According to the survival status of donors and recipients, they were divided into the graft-loss group and the graft-survival group, and the recipient death group and survival group, respectively. Univariate comparison between groups was performed by Log-rank test, and Cox proportional risk model was used to explore the independent risk factors for the graft and recipient survival. Results: Among the 284 children recipients, 184 cases (64.8%) were male and 100 cases(35.2%) were female, and 19 cases (6.7%) were living relative donor renal transplantation, 19 cases (6.7%) were preemptive transplantation, and 8 cases were secondary transplantation. The age of 284 recipients at the time of transplantation was 13.0 (9.0, 15.0) years, among whom 29 cases aged 0-6 years, 96 cases aged 7-11 years old, and 159 cases aged 12-18 years. The 1, 3, and 5 year survival rates were 92.3%, 88.9% and 84.8% for the kidney grafts, and were 97.1%, 95.6% and 94.4% for the recipients, respectively. Multivariate analysis showed postoperative acute rejection (HR=3.14, 95%CI 1.38-7.15, P=0.006) and perioperative vascular complications (HR=4.73, 95%CI 2.03-11.06, P<0.001) were independent risk factors for the survival of kidney graft. Postoperative infection (HR=14.23, 95%CI 3.45-58.72, P<0.001) was an independent risk factor for the postoperative mortality of recipients. Conclusions: Pediatric kidney transplantation shows a good short-and mid-term prognosis. Postoperative acute rejection and perioperative vascular complications are the risk factors for the survival of kidney graft, and postoperative infection is the risk factor affecting the survival of recipient.
Child ; Female ; Graft Rejection ; Graft Survival ; Humans ; Kidney Transplantation/adverse effects* ; Living Donors ; Male ; Postoperative Complications ; Prognosis ; Retrospective Studies ; Risk Factors

This study aimed to investigate the effect of methyl eugenol(ME) on hypoxia/reoxygenation(H/R)-induced injury of human renal tubular epithelial HK-2 cells and its mechanism. The viability of HK-2 cells cultured with different concentrations of ME and exposed to H/R was detected by cell counting kit-8(CCK-8) assay. The effect of ME on the morphology of HK-2 cells was observed under an inverted microscope. The content of intracellular reactive oxygen species in different groups was detected after 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA) fluorescence staining. Cell apoptosis was determined by flow cytometry. Changes in mitochondrial membrane potential were monitored by JC-1 dye. The concentrations of nuclear factor erythroid 2 related factor 2(Nrf2), heme oxygenase-1(HO-1), and nicotinamide adenine dinucleotide phosphatase oxidase 4(Nox4) were measured by Western blot, followed by the assay of Nrf2 concentration changes in cytoplasm and nucleus by confocal fluorescence staining. The results showed that when the concentration of ME was 0-40 μmol·L~(-1), the activity of HK-2 cells was not affected. Compared with the model group, ME enhanced the activity of HK-2 cells and the cell morphology was normal. As revealed by further experiments, ME inhibited the release of reactive oxygen species and the decline in mitochondrial membrane potential of HK-2 cells after H/R injury, promoted Nrf2/HO-1 expression and Nrf2 translocation to the nucleus, and down-regulated the expression of Nox4, thereby significantly reducing apoptosis. This protective effect of ME could be reversed by the specific Nrf2 inhibitor ML385. These findings have preliminarily proved that ME effectively protected HK-2 cells against H/R injury, which might be related to its promotion of Nrf2/HO-1 signaling pathway and inhibition of Nox4. Such exploration on the possible mechanism of ME in the treatment of renal ischemia-reperfusion injury(IRI) and protection of organ function from the perspective of antioxidant stress has provided reference for related research on the treatment of acute kidney injury with traditional Chinese medicine.
Apoptosis ; Epithelial Cells/metabolism* ; Eugenol/pharmacology* ; Heme Oxygenase-1/metabolism* ; Humans ; Hypoxia ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Reactive Oxygen Species ; Reperfusion Injury/drug therapy*

Objective To understand the distribution and characteristics of historical Oncomelania hupensis snail environ-ments in Baoshan District,Shanghai City,so as to provide the reference for adjusting and formulating the monitoring program of the snail situation in the future.Methods A retrospective survey and a field survey were conducted to collect the information of historical O.hupensis snail environments and set up the database.The distribution and characteristics of them were analyzed.Re-sults There were 53 historical O.hupensis snail environments which distributed in three towns,and the accumulative area was 1 635 530 m2in Baoshan District,Shanghai City.Class Ⅰ,Ⅱ,Ⅲ and Ⅳ accounted for 73.58％,5.66％,16.98％and 3.77％re-spectively.The complete transformation(Class Ⅰ and Class Ⅱ)was done in 42 places which covered the area of 1 622 043 m2,in which Class Ⅰ environments and Class Ⅱ environments accounted for 79.25％and 99.18％of the total,respectively.Conclu-sions There has been a great change in the historical O.hupensis snail environments in Baoshan District,Shanghai City.The information of the field investigation should be enriched and updated at different times to guide the investigation of O.hupensis snails in the future.

BACKGROUNDCoronary intervention therapy is the main treatment for uremic patients with coronary heart disease. The studies on whether dialysis reduces the efficacy of dual antiplatelet drugs are limited. The aim of this study was to examine the effect of dialysis on antiplatelet drugs in uremic patients with coronary heart disease.

METHODSThis study included 26 uremic patients who had undergone percutaneous coronary intervention in China-Japan Friendship Hospital from November 2015 to May 2017. We examined their thromboelastography results before and after hemodialysis. Self-paired t-tests were employed to analyze changes in the inhibition rate of platelet aggregation.

RESULTSThe mean inhibition rates of arachidonic acid-induced platelet aggregation before and after hemodialysis were 82.56 ± 2.79% and 86.42 ± 3.32%, respectively (t= -1.278, P= 0.213). The mean inhibition rates of adenosine diphosphate-induced platelet aggregation before and after hemodialysis were 67.87 ± 5.10% and 61.94 ± 5.90%, respectively (t = 1.425, P= 0.167). There was no significant difference in the inhibition rates of platelet aggregation before or after hemodialysis. These results also applied to patients with different sensitivity to aspirin and clopidogrel.

CONCLUSIONDialysis did not affect the antiplatelet effects of aspirin and clopidogrel in uremic patients with coronary heart disease.

OBJECTIVETo study the serum lipid panels in consecutive autoimmune pulmonary alveolar proteinosis(APAP)patients and analyze their relationship with anti-granulocyte macrophage-colony stimulating factor(GM-CSF)antibody and other markers.

METHODSThirty-two non-diabetic APAP patients were enrolled in the study. Serum lipids of these patients and 100 healthy volunteers were tested after an overnight fasting. Anti-GM-CSF antibody levels were measured with enzyme-linked immunosorbent assay. The correlation of serum lipids with lactate dehydrogenase,carcinoembryonic antigen,pulmonary function,and artery blood gas parameters were analyzed.

RESULTSTotal cholesterol and low-density lipoprotein cholesterol levels [(5.54±0.99)and(3.73±0.83)mmol/L respectively] were significantly higher in APAP patients than in healthy volunteers [(5.05±0.97)and(3.17±0.89)mmol/L respectively](all P<0.05). High-density lipoprotein cholesterol(HDL-C)level of the APAP group [(1.10±0.18)mmol/L ]was significantly lower than that of the healthy group(P<0.05). Low-density lipoprotein/HDL and total cholesterol/HDL ratios in the APAP group(3.47±0.90 and 5.14±1.12 respectively)were significantly higher than those in the healthy group[(2.63±0.87)and(4.18±1.12)](all P<0.05). There was no significant difference in triglyceride level between the two groups(P>0.05). HDL-C level was negatively correlated with alveolar-arterial oxygen pressure difference(r=-0.436,P<0.05)and positively correlated with arterial oxygen saturation(r=0.459,P<0.05). None of the lipid markers correlated with serum anti-GM-CSF antibody levels(all P>0.05).

CONCLUSIONSAPAP patients were likely to suffer from disturbed lipid metabolism,which was correlated with disease severity to some degree. Lipid markers deserved more attention in the management of APAP patients.

Antibodies ; blood ; Autoimmune Diseases ; epidemiology ; metabolism ; Biomarkers ; blood ; Cholesterol ; blood ; Enzyme-Linked Immunosorbent Assay ; Granulocyte-Macrophage Colony-Stimulating Factor ; metabolism ; Humans ; Lipid Metabolism ; Lipids ; blood ; Lipoproteins, LDL ; blood ; Lung ; physiopathology ; Pulmonary Alveolar Proteinosis ; epidemiology ; metabolism

Objective To explore the self-face recognition and its relationship to empathy in patients with schizophrenia.Methods Sixty-two schizophrenic patients and fifty -four healthy subjects were assessed with the self-face recognition task (SFRT) and the interpersonal reactivity index-C (IRI-C).Results The SFRT reaction time in the patients group( (2188 ± 1138) ms) was significantly longer than that in the control group( ( 1152 ± 326) ms) (P ＜ 0.01 ) ;the accuracy in the patients group ( (80 ± 16) ％ ) was significantly lower than that in the control group ( (88 ± 6) ％ ) (P ＜ 0.01 ).The IRI-C total scores,the subscores in perspective taking,the subscores in fantasy and empathic concern of IRI-C were significantly lower in the patients group(respectively(44.82 ± 10.50),(8.98 ± 3.56),( 11.87 ± 4.38 ),( 14.73 ± 4.00) ) than those in the control group ( respectively (49.85 ± 10.28),( 10.78 ± 3.86),( 14.98 ± 6.12),( 17.39 ± 4.56) ) ; the subscore in personal distress of IRI-C in the patients group(9.37 ± 5.12) was significantly higher than those in the control group(6.52 ± 3.89) ( P＜ 0.01 ).There was significant positive correlation between the accuracy for self-face recognition in SFRT and the subscore in fantasy of IRI-C ( r =0.322,P ＜ 0.05 ),the reaction time of SFRT had significantly positive correlation with the subscore in personal distress.Conclusion Schizophren patients have general impairments of self-face recognition and empathic abilities,and the self-face recognition is related to the empathic abilities.

Objective To investigate the changes of cognitive impairment and its correlated factors in patients with first acute cerebral ischemic stroke.Methods Five hundred and sixty-eighty patients,admitted to our hospital from July 2010 to June 2011 and met the diagnostic criteria of first acute cerebral ischemic stroke,were chosen in our study; neuropsychological evaluation was conducted within 1 week of acute cerebral ischemic stroke.The comprehensive neuropsychological evaluation battery included mini-mental state examination (MMSE),Digit span,Mattis dementia scale,Rey complex figure test,stroop test,World Health Organization and University of California-Los Angeles auditory verbal learning test,semantic category verbal fluency test and clock drawing test,which contained tests for memory,attention,executive function,information processing capability,visuospatial and visuo constructive functions.Gender,age,histories of hypertension and smoking,and levels of blood pressure,random blood glucose,fasting blood glucose and 2-hour postprandial blood glucose,cholesterin,triglyceride,low density lipoprotein-C (LDL-C) and high density lipoprotein-C (HDL-C) were noted and the relations between cognitive function and both blood sugar and blood lipid levels were analyzed.Results (1) The abnormal rates of these patients in MMSE,Mattis dementia scale,attention deficit disorder,immediate logical memory disorder,delayed logical memory disorder,instant auditory memory disorder,delayed auditory memory disorder,visual memory disorder,executive function disorder,information processing disorder,and visuospatial and visuo constructive disorder were 78.2％,72.5％,26.5％,56.3％,60.9％,74.6％,98.2％,83.8％,62.7％,4.9％ and 77.7％,respectively.In patients with different blood glucose levels,significant differences were found on scores of MMSE,Mattis dementia scale,attention scale (P＜ 0.05); furthermore,the scores ofMMSE,Mattis dementia scale,attention scale in patients with impaired fasting glucose were obviously lower as compared with those in other groups (P＜0.05).The scale of above cognitive domains showed no significant difference in patients with different types of hyperlipidemias (P＞0.05); the scores of execution ability and visual space structure capability in patients with HDL-C were higher than those in normal density lipoprotein-C and LDL-C (P＜0.05),and the higher level of density lipoprotein-C,the higher scores of visual space structure capability (P＜0.05).Logistic regression analysis found that the total MMSE scores were associated with gender,age,and levels of fasting blood glucose and 2-hour postprandial blood glucose; the independent risk factors of executive function were gender,age and HDL-C level; the ability of memory was correlated with age and HDL-C level.Visuospatial and visuo constructive function was associated with gender,age and mRS scores; the information processing ability was only correlated with HDL-C level.Conclusion In patients with acute cerebral ischemic stroke,the cognitive impairment is extensive and severe,with a prevalence of about 75％,mainly having disorders in memory,executive ability,spatial structure; glucose levels,especially impaired fasting glucose level show most obvious influence in cognitive impairment;HDL-C level helps keep normal cognitive function; age,gender,HDL-C level are the most important factors of cognitive function.