The effect and mechanism of metformin on peripheral neuropathy in type 1 diabetic rats / 药学学报

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

Erratum: Author correction to "YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer" Acta Pharmaceutica Sinica B 12 (2022) 2845-2858

[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].

Pharmacokinetic effects of metformin hydrochloride, food and alcohol on Ramulus Mori (Sangzhi) alkaloids / 药学学报

Ramulus Mori (Sangzhi) alkaloids (SZ-A) are a group of polyhydroxy alkaloids extracted and isolated from the traditional Chinese medicine mulberry twig, which is mainly used for the treatment of type 2 diabetes mellitus (T2DM). In addition to acting as a glycosidase inhibitor in the small intestine after oral administration, SZ-A can also be absorbed into blood and widely distributed to target organs related to diabetes, exerting multiple pharmacological effects. It is important to elucidate the possible pharmacokinetic influences of SZ-A for its clinical rational applications, such as drug interactions, the effects of food and alcohol on the absorption of SZ-A. However, studies in this area are limited. Therefore, the pharmacokinetic interactions between orally administrated SZ-A (50 mg·kg-1) and metformin hydrochloride (Met, 200 mg·kg-1) in Sprague-Dawley (SD) rats were examined. Then, the effect of food (standard feed) on the pharmacokinetics of SZ-A was investigated using fasting administration of SZ-A (50 mg·kg-1) in rats as a control. Finally, we investigated the pharmacokinetic characteristics of SZ-A (50 mg·kg-1) in different concentrations alcohol solutions using aqueous solution of SZ-A administered to rats as a control to evaluate the effect of alcohol on the bioabsorption of SZ-A. The results showed no significant pharmacokinetic interactions between SZ-A and Met after combination treatment. The standard feed had little effect on the pharmacokinetic profile of SZ-A. Alcohol retarded the absorption of SZ-A, resulting in a significant decrease in the Cmax of SZ-A. The decrease was greater at higher alcohol concentrations; however, no significant difference was observed in the AUC0-t. These results support the clinical rational applications of SZ-A. All animal protocols were approved by the Ethics Committee of Kangtai Medical Laboratory Service Hebei Co., Ltd. (Hebei, China) (No. MDL2022-01-17-1).

Research progress of biomimetic nano drug delivery system in nervous system disease / 药学学报

Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.

Research progress of anti-tumor in situ gel delivery system / 药学学报

Cancer is the most important leading cause of death worldwide, with about 10 million deaths caused by cancer in 2020. In situ gel drug delivery systems have attracted much attention in the field of pharmacy and biotechnology due to their good histo-compatibility, excellent injectability, high drug delivery capacity, slow-release drug delivery, and less influence by the in vivo environment. Meanwhile, in situ gel can be combined with chemotherapy, photo-thermal therapy, chemokinetic therapy, immunotherapy and so on to deliver drugs into the tumor site in a less invasive way without surgical operation, forming a semi-solid gel reservoir in the tumor site to realize in situ tumor combined therapy. In this paper, the author summarized the research progress of anti-tumor in situ gel delivery system in the past 10 years, introduced its commonly used polymer materials, classification principles and specific application examples, and finally summarized and discussed the key issues, in order to provide reference for the development of new anti-tumor drug delivery system in the future.

Clinicopathological characteristics and endoscopic treatment efficacy of de novo early colorectal cancer / 中华消化内镜杂志

Objective:To analyze the clinicopathological features of de novo early colorectal cancer and to evaluate the efficacy of endoscopic treatment.Methods:Patients with de novo early colorectal cancer who underwent endoscopic resection in Beijing Friendship Hospital, Capital Medical University from June 2020 to May 2022 were enrolled. The baseline data, endoscopic manifestations, treatment methods, postoperative pathological results and prognosis of the patients were collected retrospectively.Results:A total of 33 patients with de novo early colorectal cancer were enrolled with the age of 62.67 ± 8.62 years, and the male to female ratio was 7.25∶1. The long diameter of lesions was 0.96 ± 0.36 cm. The lesion morphology was mainly superficial phenotype (type 0-Ⅱ), accounting for 72.7% (24/33). Endoscopic submucosal dissection (ESD) was performed in 29 cases and endoscopic mucosal resection (EMR) was performed in 4 cases. Postoperative pathology showed that 11 cases (33.3%) were well differentiated tubular adenocarcinoma, of which the superficial submucosal layer was invaded in 2 cases. Twenty cases (60.6%) were moderately differentiated tubular adenocarcinoma, of which the superficial submucosa layer was invaded in 5 cases and the deep submucosa layer in 15 cases. Two cases (6.1%) were moderately-poorly differentiated tubular adenocarcinoma, where the deep submucosa layer was invaded in both. There was significant correlation between the depth of invasion and the degree of differentiation ( P<0.001), and moderately and moderately-poorly differentiated lesions were more likely to invade the deep submucosa layer. The en bloc resection rate was 100.0% (33/33), the complete resection rate was 97.0% (32/33), and the curative resection rate was 42.4% (14/33). Among the 19 patients who did not achieve curative resection, 13 patients received supplementary surgical treatment. No tumor residue or lymph node metastasis was found in the postoperative pathology. All patients were followed up for 3-25 months, and no signs of local recurrence or metastasis were found. Conclusion:Most de novo early colorectal cancers are superficial phenotype under endoscopy. The pathology is mainly moderately differentiated tubular adenocarcinoma. Endoscopic resection of de novo early colorectal cancer shows encouraging short-term efficacy.

S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

Course of disease and related epidemiological parameters of COVID-19: a prospective study based on contact tracing cohort / 中华预防医学杂志

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.

Preliminary observation on endoscopic treatment for polyps in appendix cavity / 中华消化内镜杂志

From January 2016 to December 2020, 6 cases of polyps in the appendix cavity with a diameter of 0.3-1.3 cm were treated by endoscopy in the Department of Gastroenterology of Beijing Friendship Hospital, Capital Medical University. All 6 cases underwent endoscopic treatment successfully, including 3 cases of en bloc endoscopic mucosal resection (EMR), 1 case of piecemeal EMR, 1 case of endoscopic submucosal dissection (ESD), and 1 case of removed by cold forceps. No complications such as bleeding, perforation, infection or acute appendicitis occurred.The wound healed well with no recurrence after re-examination in 3 cases, and 3 others were not re-examined by colonoscopy yet. The results preliminarily confirmed that endoscopic treatment of intraluminal polyps in the appendix cavity is safe and effective.

Efficacy of endoscopy for early nonampullary duodenal cancer / 中华消化内镜杂志

Objective:To evaluate the clinical efficacy of endoscopic treatment for early nonampullary duodenal cancer.Methods:Data of patients with early nonampullary duodenal cancer, who underwent endoscopic treatment from January 2015 to January 2021 at Beijing Friendship Hospital were retrospectively analyzed. Baseline data, endoscopic treatment methods, wound closure, pathology, the occurrence and outcome of complications of patients were studied.Results:A total of 47 patients who successfully went through endoscopic treatment were enrolled. Seventeen cases received endoscopic mucosal resection (EMR), 5 cases received endoscopic submucosal dissection (ESD), and 7 cases received ESD+EMR (hybrid ESD). Six cases were converted to hybrid ESD due to difficulty in ESD. Four cases received full-thickness resection with over-the-scope clip system (OTSC), and 8 cases received endoscopic piecemeal mucosal resection (EPMR). Among the 47 cases of early cancer, the en bloc resection rate was 83.0% (39/47), and the complete resection rate was 85.1% (40/47). Four patients (8.5%) had perforation which occurred at the duodenal descending part during the perioperative period, among whom, 2 patients (4.3%) recovered after endoscopic treatment, 2 others (4.3%) recovered after surgical intervention. There were no complications such as postoperative bleeding or infection during the perioperative period.Conclusion:Endoscopic treatment for early nonampullary duodenal cancer is safe and effective. A specific treatment plan can be selected according to the location, size and specific conditions of the lesion. For the operation of the descending part, it is necessary to be more vigilant to against the occurrence of perforation complications.

Therapeutic effect of endoscopy on early cancer of duodenal papilla / 中华消化内镜杂志

Objective:To evaluate the clinical efficacy of endoscopy for early cancer of duodenal papilla.Methods:A retrospective analysis was performed on data collected from 23 consecutive patients with early cancer of duodenal papilla, who underwent endoscopic treatment from January 2015 to January 2021 in Beijing Friendship Hospital. Baseline data, endoscopic and pathological data, occurrence and outcome of complications were studied.Results:Twenty-three patients successfully received endoscopic treatment. The maximal diameter of lesions evaluated under endoscopy was 1.90±0.83 cm. Among the 23 cases, 20 underwent endoscopic mucosal resection and 3 underwent endoscopic piecemeal mucosal resection. Delayed bleeding occurred in 5 cases (21.7%), 3 patients (13.0%) developed postoperative hyperamylasemia, 6 patients (26.1%) developed mild acute pancreatitis, and 1 patient (4.3%) had pancreatic duct stent displacement after the operation, which improved after medical or endoscopic treatment. No perforation occurred during the perioperative period. In terms of final pathology, the en bloc resection rate was 82.6% (19/23), and the complete resection rate was 78.3% (18/23). Preoperative endoscopic ultrasonography showed that 19 lesions were confined to the mucosal layer, which were all demonstrated by postoperative pathology. Four other cases were suspected to be involved in the submucosa or the end of the pancreaticobiliary duct under endoscopic ultrasonography, two of which were confined to the mucosal layer, and the other 2 cases involved the submucosal layer, so additional surgery was performed. A total of 18 patients were followed up, among whom 14 achieved complete resection of postoperative pathology, and 2 patients (14.3%, 2/14) were found to have recurrence at 12 and 51 months respectively after the treatment and did not relapse after surgical treatment and endoscopic treatment respectively. Among 4 other patients of follow-up whose pathology did not achieve complete resection, 1 had no recurrence, and the other 3 received additional surgical treatment without recurrence.Conclusion:Endoscopic treatment for early cancer of duodenal papilla is safe and effective. It is necessary to improve preoperative evaluation, stay alert to perioperative complications, and pay attention to regular postoperative endoscopic follow-up.

Application of rubber band traction to endoscopic submucosal dissection / 中华消化内镜杂志

Objective:To evaluate the efficacy and safety of rubber band traction-assisted endoscopic submucosal dissection (ESD).Methods:A total of 49 patients with rectal endocrine tumor who underwent ESD at Beijing Friendship Hospital Affiliated to Capital Medical University from January 2016 to December 2019 were reviewed. Thirty-two patients who underwent traditional ESD from January 2016 to May 2018 were assigned to the non-traction group. Seventeen patients who underwent the operation with a rubber band as auxiliary traction from June 2018 to December 2019 were assigned to the traction group. Basic information, ESD procedure time, complications were compared between the two groups.Results:There were no significant differences in age, gender or lesion size between the traction group and the non-traction group ( P>0.05). The ESD operation time of the traction group was significantly shorter than that of the non-traction group (13.76±5.71 min VS 22.99±10.32 min, t=-3.408, P=0.001). There were no postoperative complications in the traction group, but 3 cases of perforation occurred in the non-traction group. There was no significant difference in the incidence of perforation between the two groups ( P=0.542). Conclusion:Rubber band traction can safely improve the efficiency of ESD.

Analysis of the influence of learning engagement, interactive behavior and learning motivation on learning effect on online learning of Physiology course / 中华医学教育探索杂志

Objective:To analyze the online learning behaviors and learning results of students under different teaching modes with different learning motivations, and to provide a reference for optimizing the development of online teaching.Methods:Samples of students taking the physiology small private online course (SPOC) in 2019 and 2020, and students taking the massive open online courses (MOOC) in the same year were selected in the study to discuss the differences in learning behaviors of students under different teaching modes and learning effects on students with different learning motivations. The online learning behaviors of students were analyzed based on their learning engagement, interactive behavior and learning motivation. SPSS 25.0 was used to analyze the data with statistical methods such as function calculation, frequency statistics, regression analysis, rank sum test, correlation test and chi-square test.Results:The learning participation level ( z=14.36, P<0.001), and the human-machine and interpersonal learning interaction level ( z=-11.70, -16.18, both P<0.001) of SPOC learners in 2020 were higher than those in 2019. The overall interactive level was moderately correlated with performances of students ( r=0.42, 0.52, both P<0.001), and the correlation between interpersonal behavior and grades was much more stronger ( r=0.60, 0.55, both P<0.001). The performance composition of SPOC and MOOC learners in 2019 was completely different ( χ2=857.45, P<0.001). The learning effect of externally motivated students was significantly better than that of internally motivated students ( z=-28.42, P<0.001). Conclusion:The teaching mode adopted by the school can affect the learning effect by influencing the students' online learning engagement and interactive behavior. Besides, students' own learning motivation also plays a key role in their academic performance.

YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer

PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells, we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo. Taken together, our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.

Inhibitory effect of LZJ541, a novel small molecule inhibitor of STAT3, on the proliferation of hepatocellular carcinoma cells / 药学学报

Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC50) was 13.8 μmol·L-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC50: 41.99 μmol·L-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.

Clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children / 中国当代儿科杂志

OBJECTIVES@#To study the clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children.@*METHODS@#The medical data of 200 children with epilepsy who underwent a genetic analysis of epilepsy by the whole exon sequencing technology were collected retrospectively, of whom 9 children with epilepsy had 16p11.2 microdeletion. The clinical phenotype and genetic features of the 9 children with 16p11.2 microdeletion were analyzed.@*RESULTS@#The detection rate of 16p11.2 microdeletion was 4.5% (9/200). The 9 children with 16p11.2 microdeletion were 3-10 months old. They experienced focal motor seizures with consciousness disturbance, and some of the seizures developed into generalized tonic-clonic seizures. The interictal electroencephalogram showed focal or multifocal epileptiform discharge, and all 9 children responded well to antiepileptic drugs. The 9 children had a 16p11.2 deletion fragment size of 398-906 kb, and the number of deleted genes was 23-33 which were all pathogenic mutations. The mutation was of maternal origin in 2 children, of paternal origin in 1 child, and de novo in the other children.@*CONCLUSIONS@#16p11.2 microdeletion can be detected in some children with epilepsy. Most of the 16p11.2 microdeletion is de novo mutation and large gene fragment deletion. The onset of 16p11.2 microdeletion-related epilepsy in children is mostly within 1 year of life, and the epilepsy is drug-responsive.

Diagnostic value of endoscopic ultrasound-guided fine-needle aspiration for pancreatic lesions with liver lesions / 中华消化内镜杂志

Clinical data of 5 patients with pancreatic and liver lesions who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the Department of Gastroenterology of Beijing Friendship Hospital from February to May 2020 were analyzed retrospectively. Pancreatic lesions were located in the head of pancreas in 3 cases, the neck of pancreas in 1 case and the body of pancreas in 1 case, with the maximum diameter of 3.2-4.6 cm. The histological and cytologic results of pancreas were all positive in 5 patients after 2-4 needles of aspiration. Three patients had single lesion in left lobe of liver, 1 had multiple lesions in left lobe of liver, and 1 had multiple lesions in left and right lobe of liver. The maximum diameter of liver lesions were 0.4-1.2 cm. After 1-3 needles of aspiration, the histological and (or) cytologic results of liver were positive in 4 of 5 patients, only 1 patient's cytologic result was negative. No associated complications were recorded. EUS-FNA for pancreatic and liver lesions is safe and effective.

Validation of compound C19 as a glutaminase C inhibitor / 药学学报

The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.

A novel PI3K inhibitor XH30 suppresses orthotopic glioblastoma and brain metastasis in mice models

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.

The regulatory role of E2F1 in prostate cancer / 药学学报

E2F transcription factor 1 (E2F1) is a major member of the E2F transcription factor family and participates in a wide range of physiological regulatory processes, such as cell cycle, survival, apoptosis, and metabolism. It is proved that the activity of E2F1 is related to the G1/S phase regulation of the cell cycle dependent on tumor suppressor retinoblastoma protein (RB). Recent studies have shown that E2F1 is highly expressed in prostate cancer cells, manifested as an oncogene, and its expression level is closely related to the occurrence, development, and poor clinical prognosis of prostate cancer. Androgen receptor (AR) is the main driving factor for the growth and progression of prostate cancer, and the changes of AR pathway play a key role in the pathological progression of prostate cancer. This article provide a systematic and comprehensive summary on recently published articles to review the role of the E2F1 pathway in prostate cancer.