Lei Miao

Guangzhou Medical University

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Chunhua He

Sichuan University

Xiaohong Li

Sichuan University

Jun Zhu

Sichuan University

Leni Kang

Sichuan University

Juan Liang

Guizhou University of Finance and Economics

Leaf Huang

First Affiliated Hospital of Guangdong Pharmaceutical University

Zhenjian Zhuo

Guangzhou Medical University

Li Dai

Sichuan University

Jing He

Guangzhou Medical University

Yanping Wang

Sichuan University

Cooperative Institutions

Computer Algorithms for Medicine

233

Chinese Academy of Sciences

173

Sun Yat-sen University

134

Sichuan University

126

Chinese Academy of Medical Sciences & Peking Union Medical College

University of Chinese Academy of Sciences

Shanghai Jiao Tong University

Wenzhou Medical University

Zhejiang University

Peking University

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Nanoparticles with Precise Ratiometric Co‐Loading and Co‐Delivery of Gemcitabine Monophosphate and Cisplatin for Treatment of Bladder Cancer

Advanced Functional Materials (2014)

Lei Miao Shutao Guo Jing Zhang William Y. Kim Leaf Huang

Combination chemotherapy is a common practice in clinical management of malignancy. Synergistic therapeutic outcome is only achieved when tumor cells are exposed to cells in an optimal ratio. However, due to diverse physicochemical properties of drugs, no free drug cocktails or nanomaterials are capable of co‐loading and co‐delivering drugs at an optimal ratio. Herein, we develop a novel nano‐platform with precise ratiometric co‐loading and co‐delivery of two hydrophilic drugs for synergistic anti‐tumor effects. Based on previous work, we utilize a solvent displacement method to ratiometrically load dioleoyl phosphatidic acid (DOPA)‐gemcitabine monophosphate (GMP) and DOPA coated cisplatin‐precipitate nanocores into the same PLGA NP. These cores are designed to have similar hydrophobic surface properties. GMP and cisplatin are engineered into PLGA NP at an optimal synergistic ratio (5:1, mol:mol) with over 70% encapsulation efficiency and were ratiometrically taken up by tumor cells in vitro and in vivo. These PLGA NP exhibit synergistic anti‐cancer effects in a stroma‐rich bladder tumor model. A single injection of dual drugs in PLGA NP can significantly inhibit tumor growth. This nanomaterial‐system solves problems related to ratiometric co‐loading and co‐delivery of different hydrophilic moieties and provides possibilities for co‐loading hydrophilic drugs with hydrophobic drugs for combination therapy.

PLGA

Nanomaterials

10.1002/adfm.201401076

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Citations (165)

Targeting the STING pathway in tumor-associated macrophages regulates innate immune sensing of gastric cancer cells

Theranostics (2019)

Lei Miao Jingjing Qi Qi Zhao Qi-Nian Wu Da‐Liang Wei

Rationale: STING is a critical player in the innate and adaptive immune system, sensing cytosolic DNA to activate the expression of interferon genes and regulate T lymphocytes, which drives immunogenic responses to cancer cells. Tumor-associated macrophages (TAMs), abundantly present in the tumor microenvironment, play a key role in cancer development. Gastric cancer is one of the most common and leading causes in cancer-related death worldwide. However, studies on the function and regulation of STING in TAMs and their roles in gastric cancer progression are still limited. Methods: We analyzed STING and CD68 expression of 200 pairs of gastric cancer and adjacent normal tissues by immunohistochemistry to identify the prognostic values of STING, as well as the correlations between STING and CD68 in gastric cancer. The characteristics of STING-altered macrophages, as well as their effects on cancer cell apoptosis and T cell differentiation were examined by flow cytometry. Cytokines secreted by STING-altered macrophages were identified by the Human Inflammation Array3 kit. Concentrations of soluble IL24 and IFN-β were measured by ELISA. In vivo models, including spontaneous gastric cancer in p53+/- mice and cell line-based xenografts, were established, and clinical benefits of STING-altered macrophages were examined. Results: Our study identifies STING as a prognostic factor for gastric cancer, and for the first time demonstrated that knocking-down STING and STING activation by 2'3'-c-GAMP both promote TAMs polarizing into pro-inflammatory subtype and induce apoptosis of gastric cancer cells, mechanistically through IL6R-JAK-IL24 pathway. Conclusions : This study evaluated effects of targeting STING in TAMs in anti-gastric-cancer therapies. Moreover, we unveil a novel function of STING to activate the IL6R-JAK-IL24 pathway in macrophages.

Sting

10.7150/thno.37745

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Citations (94)

Social and environmental risk factors for road traffic injuries among children under five in rural China

Medicine (2020)

Yuxi Liu Meixian Wang Leni Kang Chunhua He Lei Miao

Road traffic injuries (RTIs) have become a considerable issue for children. In China, RTIs are among the top 3 contributors to injury-related mortality and disability-adjusted life years. The present study aimed to evaluate social and environmental factors that may contribute to RTIs among children under 5 in rural areas of China.The study was based on 1 year of data (October 1, 2015 to September 30, 2016) from the National Maternal and Child Health Surveillance System (NMCHSS) from all districts in 334 National Maternal and Child Health Surveillance Districts in 30 Chinese provinces, autonomous regions, and municipalities. Data were analyzed to identify environmental, social, and primary caregiver factors related to RTIs among children under 5.Based on data for the 279 children registered in the NMCHSS during the study period, incidence of RTIs increased with increasing age and was higher for boys than girls. Risk of RTIs depended on distances from the child's home to roads and playgrounds. Enrollment in kindergarten and characteristics of primary caregivers affected risky road behaviors by children. Most primary caregivers (67.4%) reported never using child car seats, and 70.6% reported never using a child helmet. Among primary caregivers without a driver's license, 24.8% reported having driven motor vehicles or motorcycles.The living environment and behaviors of primary caregivers can affect risk of RTIs in children younger than 5 years in rural China. Road safety awareness should be strengthened at the community and kindergarten levels.

10.1097/md.0000000000019825

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Citations (9)

Diselenide-crosslinked zwitterionic nanogels with dual redox-labile properties for controlled drug release

Polymer Chemistry (2020)

Yefei Tian Lei Miao Luke Yan Feifei An

We developed a diselenide-crosslinked zwitterionic nanogel based on poly(2-methacryloyloxyethyl phosphorylcholine), which has sensitive dual redox-degradability and high colloidal stability.

Diselenide

Nanogel

Phosphorylcholine

Dual role

10.1039/d0py00004c

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Citations (50)

LncRNAs and CircRNAs in cancer

MedComm (2022)

Xin Yin Huiran Lin Lei Lin Lei Miao Jing He

Abstract It is well known that noncoding RNAs (ncRNAs) cannot encode proteins, but they can play important regulatory roles in tumors by combining with proteins, RNAs, and DNAs. As more and more studies reveal the important roles and underlying mechanisms of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in cancer, their huge application potential in cancer therapy cannot be ignored. For example, lncRNAs can be involved in tumor‐related signal transduction pathways, cell cycle control, DNA damage, epigenetic regulation, and microRNA control. A group of studies confirmed that abnormal expression of lncRNAs can affect cancer progression. Furthermore, as covalently closed continuous circular ncRNAs, many recent studies have shown that circRNAs have regulatory effects and other important biological significances in cancer. Interestingly, circRNAs were found to have translational functions. This has greatly attracted people's attention to circRNAs research. In this review, we introduce the important roles of lncRNAs and circRNAs in some representative cancers, respectively. Furthermore, we focus on the biological functions and important clinical therapeutic implications of lnRNAs and circRNAs in neuroblastoma. Our review also focuses on providing rationale and relevant references for novel biomarkers for neuroblastoma diagnosis, prognosis, and treatment.

Circular RNA

10.1002/mco2.141

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Postnatal growth in preterm infants during the first year of life: A population-based cohort study in China

PLoS ONE (2019)

Leni Kang Huiqing Wang Chunhua He Ke Wang Lei Miao

In preterm infants (i.e. the gestational age less than 37 weeks), postnatal growth remains a concern. This study used multicenter longitudinal data from China's Under 5 Child Nutrition and Health Surveillance System to investigate the postnatal growth in the weight and length of preterm infants. Gender-stratified differences in weight and length were assessed between preterm and term infants. 1221 preterm infants and 1221 matched term infants were included. The rates of growth in weight and length in preterm infants was greater than those in term infants, especially from the first to sixth month. The rates were higher in males compared to females in the first 3 months. The differences of weight and length between preterm and term infants decreased with increasing age, however, these measurements did not reach the level of their term peers until 12 months before adjusting for gestational age. The median values of weight and length were even larger in preterm infants in the first month after adjusting for gestational age.

10.1371/journal.pone.0213762

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Citations (15)

Mechanism of action of Nrf2 and its related natural regulators in rheumatoid arthritis

Journal of Orthopaedic Surgery and Research (2024)

Ke Ma Lei Miao Bo Li Wenfei Yu Fengzhao Liu

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis that can lead to joint deformities. To date, more than 18 million individuals worldwide have been diagnosed with RA, making it one of the most prevalent autoimmune diseases globally and posing a significant threat to public health and safety. Due to the complex pathogenesis of the disease, which involves autoimmunity, genetics, inflammation and oxidative stress in the body's tissues, the current drug therapy generally targets a single molecule, and effective and efficient drugs involving multiple levels and targets are lacking; thus, there is an urgent need for high-quality research and treatment in this field. Nuclear transcription factor erythroid 2-associated factor 2 (Nrf2) plays a crucial role in cellular resistance to oxidative stress and electrophilic attacks and is a potential pharmacological target for chronic disease treatment. While currently no drugs that target Nrf2 have been approved specifically for RA treatment, such an approach holds great significance. In recent years, the use of natural products to treat RA and other chronic conditions has become increasingly widespread because of their superior efficacy and minimal side effects. Therefore, this article provides a review of the mechanism of Nrf2 in RA and summarizes natural products that target Nrf2 and its associated pathways in the treatment of RA, aiming to offer new insights and strategies for the prevention and management of RA.

Mechanism of Action

10.1186/s13018-024-05221-w

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Citations (0)

P8 Hydrogen sulfide and SPRC mitigate infarct of myocardial infarction via governing migration and infilitration of macrophages

Nitric Oxide (2014)

Lei Miao Hong Xin Xiaoming Xin Yi Zhun Zhu

CD163

10.1016/j.niox.2014.03.058

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Wentilactone B induces G2/M phase arrest and apoptosis via the Ras/Raf/MAPK signaling pathway in human hepatoma SMMC-7721 cells

Cell Death and Disease (2013)

Z Zhang Lei Miao Cuiting Lv Han‐Dong Sun Wei Sun

Hepatocellular carcinoma (HCC) is generally acknowledged as the most common primary malignant tumor, and it is known to be resistant to conventional chemotherapy. Wentilactone B (WB), a tetranorditerpenoid derivative extracted from the marine algae-derived endophytic fungus Aspergillus wentii EN-48, has been shown to trigger apoptosis and inhibit metastasis in HCC cell lines. However, the mechanisms of its antitumor activity remain to be elucidated. We report here that WB could significantly induce cell cycle arrest at G2 phase and mitochondrial-related apoptosis, accompanying the accumulation of reactive oxygen species (ROS). Additionally, treatment with WB induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), but not p38 MAP kinase. Among the pathway inhibitors examined, only SP600125 (JNK inhibitor) markedly reversedWB-induced apoptosis, and only U0126 (ERK inhibitor) significantly blocked WB-triggered G2 phase arrest. We also found that WB treatment increased both Ras and Raf activation, and transfection of cells with dominant-negative Ras (RasN17) abolishedWB-induced apoptosis and G2 phase arrest in SMMC-7721 cells. Furthermore, the results of inverse docking (INVDOCK) analysis suggested that WB could bind to Ras–GTP, and the direct binding affinity was also confirmed by surface plasmon resonance (SPR). Finally, in vivo, WB suppressed tumor growth in mouse xenograft models. Taken together, these results indicate that WB induced G2/M phase arrest and apoptosis in human hepatoma SMMC-7721 cells via the Ras/Raf/ERK and Ras/Raf/JNK signaling pathways, and this agent may be a potentially useful compound for developing anticancer agents for HCC.

10.1038/cddis.2013.182

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Citations (83)

[Impacts of birth defects on perinatal deaths in Chinese population].

PubMed (2004)

Li Dai Guang-xuan Zhou Jun Zhu Lei Miao Yanping Wang

To examine the time trends of perinatal mortality and the frequency of birth defects occurring in perinatal deaths, and to provide a national perspective on the impacts of congenital anomalies on perinatal mortality from 1990 through 2001.Data were from Chinese Birth Defects Monitoring network-a hospital-based congenital anomalies registry system. During 1990 - 2001, all live or still births with 28 weeks of gestation or more, born in monitoring units, were studied within 7 days after delivery. The proportion of perinatal deaths due to birth defects, which was defined as the number of perinatal deaths associated with congenital anomalies per 100 perinatal deaths, was calculated by birth area (urban versus rural), geographic-economic status (coast areas, inner land areas and remote areas), to evaluate the impacts of birth defects on perinatal mortality.Perinatal mortality declined from 22.85 per 1000 in 1990 to 13.26 per 1000 in 2001, which showed a significant downward trend. Similar trend was also observed in the rate of stillbirth and the ratio of early neonatal death. However, the proportion of perinatal deaths due to birth defects had an increasing trend although the perinatal birth defects-specific death rate was declining, especially during 1996 - 2001. This result was also seen in urban and rural area, in coast regions, in inner land regions and in remote regions of China. Higher rate of birth defects occurring in perinatal deaths was observed in urban area than in rural area. Significant difference of this rate was also found among different geographic-economic regions, with the highest one in inland regions.Birth defects were accounted for an increasing proportion of perinatal deaths in China, and had become one of the major causes of perinatal deaths.

Perinatal mortality

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Citations (12)