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 explore the interventional treatment method for complex and refractory lymphatic malformation in children.Methods The clinical data of 78 cases with complex and refractory lymphatic malformation during January 2013 to January 2016 in our department were retrospectively analyzed.The lesions involved the neck in 28 cases,maxillofacial regions in 19 cases,the chest and armpit in 8 cases,the limb in 7 cases,the pelvic cavity and retroperitoneal space in 6 cases,the superior mediastinum in 3 cases,the hypogloeeis in 3 cases and scrotum or perineum region in 4 cases.All the children underwent ultrasound or MRI imaging studies preoperatively.The interventional procedures included:(1) Percutaneous puncture of the LM for sclerotherapy.The lesions were punctured with 20 G needle under the guidance of DSA or ultrasound and the correct positions were confirmed with angiography.The liquid of the lesions was extracted as far as possible.The dosage of sclerosing agents was adjusted according to the size of lesion.The dose of Laurolacrogol injection was 1/10—1/5 of the amount of the liquid in the lesions and the maximum of Laurolacrogol foam was ≤8 ml(20 mg).The dose of Pingyangmycin was ≤ 8 mg.(2) The drainage catheter placement and sclerotherapy.Percutaneous catheter drainage under ultrasound guidance or by surgery was conducted.The liquid in the lesions was drained by retaining the catheter for 1-4 weeks,and sclerotherapy was applied for several sessions during this period.(3) Treatment for one time a week,2 times a session.The interval of every two sessions was 4 weeks.The sclerosing agents included:Laurolacrogol Injection or Pingyangmycin for the lesions with high tension,Laurolacrogol foam for the lesions with low tension,Pingyangmycin for the microcystic lesions.Statistical analysis was conducted using SPSS20.0 software.Results A total of 208 sessions of sclerotherapy for 78 LM patients were performed and average session was (3.0±0.8).Nine patients used Lauromacrogol foam,23 patients used Lauromacrogol Injection,39 patients used pingyangmycin,while combined treatment was conducted in 7 patients.Laurolacrogol injection was used in 20 cases,Pingyangmycin in 29 cases and combination therapy in 5 cases for the high tension lesions in the neck,maxillofacial,chest and armpit.The low tension lesions of pelvic cavity and retroperitoneal space in 6 cases and of superior mediastinum in 3 cases were placed with draining catheters,and treated with sclerotherapy with Laurolacrogol foam.Three cases with hypogloeeis LM was neonates,who were treated with Laurolacrogol injection.The lesions on the limb and scrotum or perineum region were almost microcystic,were treated with Pingyangmycin in 9 cases and with combination therapy in 2 cases.The total curative rate was 97.4％ (76/78),total effective rate was 100％ (78/78).Imaging examinations showed that the cavities were closed or only a small amount of residual sclerotic lesions were present.Clinical examinations showed that the surface masses almost disappeared.The follow up period was 6 months to 2 years.There were no serious complication and adverse reactions occurred.Conclusions Interventional treatment is a safe,effective,and minimally invasive treatment for the complex and refractory lymphatic malformation.In order to receive the best treatment effect,we should use targeted therapy for different region and type of LM.

Objective To explore risk factors,prevention and treatment of common complications of benign esophageal stenosis treated with the retrievable covered stents in children.Methods Fifteen cases,diagnosed as benign esophageal stenosis by barium esophagogram were treated with retrievable covered stents under fluoroscopy,Then the stents were removed after 2-3 weeks.The cases were followed-up and complications were observed.Results The stents were successful implanted in all cases.The diet was improved obviously after operation,and gradually transformed from liquid,semiliquid to normal feeding.At the same time,narrow section gradually expanded from 0.1-0.6 cm to 0.6-1.5 cm.Postoperative follow-up was in 1,2,3 weeks and 3 months.Main complications were stents shift in 5 cases,esophageal restenosis in 2 cases,esophageal-tracheal fistula in 1 case,postoperative dull pain behind sternum and foreign body sensation in 6 cases.Relevant preventions and treatments were performed based on different complications.Conclusion It should not be ignored that complications after covered stent placement are more in children than in adults,preventions and treatments should be taken positively.

Objective To explore therapeutic effects of different interventional approaches to neonatal Kasabach-Merritt syndrome (K-MS) Methods A retrospective analysis of therapeutic effects of different interventional approaches to K-MS in 12 neonates from May 2010 to August 2014. All the patients received local treatment (n=5), chemoembolization (n=4) and combined local treatment and endovascular chemoembolization (n=3), respectively, depending on size, location and blood supply of K-MS. The K-MS patients with angioma measuring< 5 cm, 5 to 10 cm and >5 cm received local treatment, endovascular chemoembolization and combined local treatment and endovascular chemoembolization, respectively. The patients were categorized as cured, improved and clinical inefficient, respectively, based on therapeutic effect. The criteria for cured patients were: (1) angioma faded completely or mostly; (2) the platelet count stabilized within the normal range; (3)no recurrence for more than six months. The criteria for improved patients were: (1) angioma shrinked significantly; (2) the platelet stabilized within the normal range. The criteria for clinical inefficient patients were: (1) agioma no obviously shrinked, the platelet count has no improvement over 2 months after interventional approaches. Results All the 12 patients with K-MS were cured and had no complication. Of the 12 patients, 5 patients received local treatment had decreased localized tension and ecchymosis of hemangioma at the first day of therapy, were cured after 2 to 7 courses of therapy. Of the 4 patients received endovascular chemoembolization, 3 were cured after one course of treatment, 1 had recurrent disease one month later after one course of therapy and were cured after the second course of treatment.One had recurrent disease a month later after one course of treatment and were cured after the second course of treatment. Three received combined local treatment and endovascular chemoembolization, angioma shrinked significantly and increased platelet count after the first course of treatment, and 2 to 3 courses local treatment were combined, hemangioma faded and platelet count stabilized within the normal range after 2 to 3 courses of local treatment. Conclusions Interventional therapy is the most effective treatment of neonatal K-MS.There are different interventional approaches to optimize treatment of neonatal K-MS depending on sizes, location and blood supply of K-MS.

Objective To analyse the CT,MRI features of pleomorphic xanthoastrocytoma and improve the diagnosis.Methods Imaging feature of pleomorphic xanthoastrocytoma of 26 cases confirmed by surgery and pathology were analyzed retrospectively.Distribution,size,shape,signal,dense,peritumor edema and invasion of adjacent structures of lesion were summarized.Results The locations of lesions included:temporosphenoid lobe (19 cases),frontal lobe (2 cases),the lateral and three ventricles in 1 case,occipital lobe (1 case),medulla oblongata (1 case),and cervical cord (1 case).The tumor size:maximum:82 mm × 40 mm × 70 mm,minimum:16 mm × 13 mm × 14 mm.Solid lesions (3 cases),solid lesions with necrosis (7 cases),solid and cystic lesions (16 cases),lesion with calcification (4 cases).The solid lesions of the tumors showed equal signal intensity or slightly low signal intensity on T1WI,and equal signal intensity or slightly high signal intensity on T2WI.The equidensite and high density on CT,peritumor edema degree:mild (2 cases),moderate (5 cases),severe (1 case).Conclusion The characteristic imaging features can help in the understanding and diagnosis of pleomorphic xanthoastrocytoma.

Objective To determine the safety and efficacy of intra-arterial urokinase in the treatment of acute cerebral infarction (ACI) patients with computed tomography perfusion-based selection within a 6-9 h window.Methods Fifty-two ACI patients,with computed tomography perfusion imaging (CTPI) identifying thresholds for salvageable penumbra,were randomly assigned to intra-arterial thrombolysis with urokinase (group A) and conventional anti-platelet aggregation (group B) within a 6-9 h window.Whole brain digital subtraction angiography (DSA) was done at pre-and post-treatment to observe the recanalization of occlusive vessels in group A.The National Institutes of Health Stroke scale (NIHSS) 24 h and 7 d after treatment,and modified Rankin Scale (mRS) and Barthel Index (BI) 90 d after treatment were used to evaluate the efficacy.Results In group A,15 patients showed successful recanalization (thrombolysis in myocardial infarction [TIMI] index:grade Ⅲ in 9 and grade Ⅱ in 6) and 12 patients showed unsuccessful recanalization (TIMI index:grade Ⅰ in 6 and grade 0 in 6) with a successful recanalization rate of 55.56％.More obvious NIHSS improvement 24 h and 7 d after treatment in group A was observed than that in group B (P＜0.05),and more patients with favorable outcomes based on mRS and BI in group A were noted than those in group B (P＜0.05).In addition,the incidence of cerebral hemorrhage within 24 h of treatment between the two groups was similar (P＞ 0.05).Conclusions Intra-arterial thrombolysis with urokinase is safe and effective for ACI patients within a 6-9 hour window under the guidance of CTPI.

Objective To explore the impact of ischemic stroke on intestinal barrier changes in dogs.Methods Totally 20 mongrel dogs were divided into 2 groups by random number table with 10 in each.Double silicone cylinders measuring 1.1 mm in diameter and 8 mm in length were placed into their internal carotid arteries in all dogs of group A.Group B served as a control group and received sham operation.Light microscopy was performed for morphological measurement of intestinal epithelial cell.Immunohistochemistry was used to analysis the changes of protein zonula occludens-1(ZO-1)localizing at tight junction of intestinal epithelial cells.Results Ischemic stroke was confirmed by cranial CT scanning in all dogs of group A.Compared with the test results in group B,the occludin and Zo-1 protein levels in group A were significantly lower than those in group B(occludin:0.20 ±0.01 vs 0.22 ±0.01,P =0.007; ZO-1:0.20 ±0.01 vs 0.22 ±0.02,P =0.008).The apoptotic index in group A was significantly higher than in group B(29.04 ± 3.79 vs 6.44 ± 1.24,P =0.002).There was a positive correlation between occludin and ZO-1(R =0.71,P =0.02),and the apoptotic index was negatively correlated with levels of occludin,ZO-1(R =-0.91,P =0.00; R =-0.77,P =0.01).Light microscopy showed that the dogs in group A had intestinal mucousal injuries while no obvious change was detected in group B.Conclusions Dogs with ischemic stroke tend to develop intestinal barrier dysfunction,during which the destruction of tight junction plays a key role.The up-regulated apoptosis of intestinal epithelial cell constitutes one of the cellular bases of intestine injury.

Objective To determine the effect of local mild hypothermia on patients with acute cerebral infarction and ascertain its optimal therapeutic window. Methods According to the time receiving treatment, 114 patients with acute cerebral infarction were divided into group A (≤6 h), group B (6-24 h) and group C (≥ 24 h). Then, each group was subdivided into 2 groups at random: treatment group (A1, B1, C1) and control group (A2, B2, C2). Patients in the control group were subjected to such conventional therapy as anti-platelet aggregation. Patients in the treatment group were treated with local mild hypothermia (33-35 ℃ body-core temperature) for 48 h besides conventional therapy. Clinical outcomes were assessed by the National institutes of health stroke scale (NIHSS) on admission and 7, 14,30 d after treatment. Furthermore, we detected the serum level of nitrogen monoxidum (NO) and superoxide dismutasc (SOD) on admission, and 7 and 14 d after treatment. Results Compared with the control group, treatment group enjoyed significantly decreased scores of NIHSS 7, 14 and 30 d after treatment and significantly decreased level of NO 7 and 14 d after treatment (P＜0.05), but obviously increased SOD vitality 7 and 14 d after treatment (P＜0.05). No significant differences in terms of NIHSS scores, level of NO and SOD vitality were noted between group C1 and group C2 at each time point (P＞0.05). Group Al and group B1 had obviously lower scores of NIHSS than group C1 on the 7th, 14th and 30th d of treatment, and had significantly lower level of NO and obviously increased SOD vitality as compared with group C1 on the 7th and 14th d of treatment (P＜ 0.05), and group A1 enjoyed its advantage.Conclusion Early local mild hypothermia therapy can improve neurological function in patients with acute cerebral infarction. The mild hypothermia induced within 6 h may be optimal therapeutic window;mild hypothermia induced at 6-24 h is less effective and that above 24 h is non-effective.

OBJECTIVETo evaluate the application of hand-use ProTaper instruments in endodontic treatment of molar canals.

METHODSA total of 203 permanent molars were randomly divided into the experimental group (99 molars) and control group (104 molars) prepared by hand-use ProTaper instruments and standard stainless steel K-file, respectively. The molars in the two groups were obturated by cold lateral condensation technique. The root canal preparation and obturation were evaluated by radiograph, and the working time of preparation and post-operative emergencies were analyzed.

RESULTSThe preparation time in the experimental group was obviously shorter than that in the control group (P<0.01). The rate of satisfactory effect was significantly higher in the experimental group than in the control group (P<0.01), and the rate of post-operative emergencies was significantly lower in the experimental group (P<0.01).

CONCLUSIONThe application of hand-use ProTaper instruments may improve the effect of root canal treatment of the molars and shorten the working time and reduce the post-operative emergencies.

Adult ; Dental Instruments ; Female ; Humans ; Male ; Middle Aged ; Molar ; Root Canal Preparation ; methods ; Young Adult

OBJECTIVETo evaluate the role of gastric mucosa apoptosis in the stress of ischemic stroke, and to discuss the relationship between gastric mucosa apoptosis and gastric barrier.

METHODSTen dogs were artificially made ischemic stroke by operation (IS group), and another 10 shamly-operated dogs were served as control group. Sucrose permeability were measured after the operation. All dogs were sacrificed 24 hours after operation to measure the gastric mucosal apoptosis index, gastric gross classification, and histological score.

RESULTSThe gastric mucosal apoptosis index in the IS group were significantly higher than in the control group (14.83 +/- 4.41 vs. 5.60 +/- 2.61, P < 0.05). The gastric mucosal apoptosis index were correlated with the sucrose permeability (r = 0. 89, P < 0.05) , gastric gross classification (r = 0. 87, P < 0.05), and histological score (r = 0.92, P < 0.05).

CONCLUSIONSAlthough ischemic stroke will not cause the obvious damage in the respiratory and circulatory system, it is responsible for the apoptosis of epithelial cell in the gastric mucosa and gastric barrier dysfunction. The apoptosis index is closely correlated with the damage of the function and morphology of the gastric barrier, indicating that the epithelial cell apoptosis acceleration in the gastric mucosa may result in the damage of gastric barrier function.

Animals ; Apoptosis ; physiology ; Dogs ; Epithelial Cells ; pathology ; Gastric Mucosa ; pathology ; In Situ Nick-End Labeling ; Random Allocation ; Stroke ; pathology ; physiopathology