NG2-Glia Cause Diabetic Blood-Brain Barrier Disruption by Secreting MMP-9.

Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/ß-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of ß-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion: The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/ß-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

Function of the GABAergic System in Diabetic Encephalopathy.

Diabetes is a common metabolic disease characterized by loss of blood sugar control and a high rate of complications. γ-Aminobutyric acid (GABA) functions as the primary inhibitory neurotransmitter in the adult mammalian brain. The normal function of the GABAergic system is affected in diabetes. Herein, we summarize the role of the GABAergic system in diabetic cognitive dysfunction, diabetic blood sugar control disorders, diabetes-induced peripheral neuropathy, diabetic central nervous system damage, maintaining diabetic brain energy homeostasis, helping central control of blood sugar and attenuating neuronal oxidative stress damage. We show the key regulatory role of the GABAergic system in multiple comorbidities in patients with diabetes and hope that further studies elucidating the role of the GABAergic system will yield benefits for the treatment and prevention of comorbidities in patients with diabetes.

Neuritin Promotes Bone Marrow-Derived Mesenchymal Stem Cell Migration to Treat Diabetic Peripheral Neuropathy.

The purpose of this study is to explore the effect and mechanism of neuritin overexpression in the bone marrow on peripheral neuropathy in type 2 diabetic (db/db) mice. We analyzed the impact of bone marrow neuritin overexpression on diabetic peripheral neuropathy and migration of bone marrow mesenchymal stem cells in db/db mice. Antagonists were used to inhibit the stromal cell-derived factor (SDF)-1α/C-X-C chemokine receptor type 4 (CXCR4)-phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in primary cultured bone marrow mesenchymal stem cells. Immunofluorescence, transmission electron microscopy, Oil Red O staining, and transwell migration assays were used. Bone marrow-specific overexpression of neuritin in db/db mice was successfully established. Overexpression of neuritin in the bone marrow ameliorated hyperglycemia, prevented diabetic peripheral neuropathy, protected the ultrastructure of the sciatic nerve and intra-epidermal nerve fiber density, and promoted Schwann cell proliferation and remyelination in the sciatic nerve. Moreover, it ameliorated fat accumulation, adipocyte number, and vascular and nerve densities; decreased glutamate content in serum and bone marrow; restored gradient SDF-1α contents between bone marrow, blood, and sciatic nerve; and promoted impaired diabetic bone marrow mesenchymal stem cell migration. Neuritin improves bone marrow mesenchymal stem cell migration via the SDF-1α/CXCR4-PI3K/Akt signaling pathway in vitro. Overexpression of neuritin in the bone marrow can locally ameliorate neuropathy in the bone marrow. This improves the migration capability of bone marrow mesenchymal stem cells and repairs diabetic peripheral neuropathy, at least partly by activating the PI3K/Akt pathway through the SDF-1α/CXCR4 axis.

NG2-glia crosstalk with microglia in health and disease.

Neurodegenerative diseases are increasingly becoming a global problem. However, the pathological mechanisms underlying neurodegenerative diseases are not fully understood. NG2-glia abnormalities and microglia activation are involved in the development and/or progression of neurodegenerative disorders, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and cerebrovascular diseases. In this review, we summarize the present understanding of the interaction between NG2-glia and microglia in physiological and pathological states and discuss unsolved questions concerning their fate and potential fate. First, we introduce the NG2-glia and microglia in health and disease. Second, we formulate the interaction between NG2-glia and microglia. NG2-glia proliferation, migration, differentiation, and apoptosis are influenced by factors released from the microglia. On the other hand, NG2-glia also regulate microglia actions. We conclude that NG2-glia and microglia are important immunomodulatory cells in the brain. Understanding the interaction between NG2-glia and microglia will help provide a novel method to modulate myelination and treat neurodegenerative disorders.

The serotonergic system dysfunction in diabetes mellitus.

Most peripheral serotonin (5-HT) is synthesized in enterochromaffin cells, and most circulating 5-HT is stored in platelets. As a monoamine, 5-HT has several functions in various non-neuronal and neuronal systems. In the central nervous system, it functions as a neurotransmitter to modulate feeding behavior and mood. Numerous clinical trials have focused on increasing 5-HT activation in the central nervous system, including those involving anti-obesity drugs currently in the market, although severe side effects on peripheral system can lead to the withdrawal of certain drugs. Recent studies have revealed that both the peripheral and central serotonergic systems play a vital role in diabetes and its complications. This review summarizes the roles of the serotonergic system in blood glucose regulation, diabetic macroangiopathy, diabetic peripheral neuropathy, and diabetic encephalopathy, indicating its potential clinical significance as a therapeutic target for the treatment of diabetes and its complications.

Glial and Vascular Cell Regulation of the Blood-Brain Barrier in Diabetes.

As a structural barrier, the blood-brain barrier (BBB) is located at the interface between the brain parenchyma and blood, and modulates communication between the brain and blood microenvironment to maintain homeostasis. The BBB is composed of endothelial cells, basement membrane, pericytes, and astrocytic end feet. BBB impairment is a distinguishing and pathogenic factor in diabetic encephalopathy. Diabetes causes leakage of the BBB through downregulation of tight junction proteins, resulting in impaired functioning of endothelial cells, pericytes, astrocytes, microglia, nerve/glial antigen 2-glia, and oligodendrocytes. However, the temporal regulation, mechanisms of molecular and signaling pathways, and consequences of BBB impairment in diabetes are not well understood. Consequently, the efficacy of therapies diabetes targeting BBB leakage still lags behind the requirements. This review summarizes the recent research on the effects of diabetes on BBB composition and the potential roles of glial and vascular cells as therapeutic targets for BBB disruption in diabetic encephalopathy.

Neuritin inhibits astrogliosis to ameliorate diabetic cognitive dysfunction.

Earlier, it was shown that reversing the downregulation of neuritin expression in the brain improves central neuropathy in diabetic rats. We investigated the protective mechanism of neuritin in diabetic cognitive dysfunction via astrocytes. Further, the impact of the overexpression of neuritin in the cortex and the hippocampus on diabetic cognitive dysfunction and astrogliosis in type 2 diabetic (db/db) mice was assessed. Antagonists were used to inhibit the JAK2/STAT3 signaling pathway in U-118MG, an astrocyte cell line. Immunofluorescence, Western blotting, and real-time PCR were performed. Neuritin overexpression in the hippocampus of db/db mice significantly ameliorated cognitive dysfunction, hippocampal neuronal impairment, and synaptic plasticity deterioration, and inhibited astrogliosis and the JAK2/STAT3 signaling pathway in the hippocampus. Neuritin suppressed the JAK2/STAT3 signaling pathway to inhibit lipopolysaccharide-induced gliosis in U-118MG cells. It was observed that neuritin regulates the JAK2/STAT3 signaling pathway in astrocytes to inhibit astrogliosis and improve diabetic cognitive dysfunction.

Differential Modulators of NG2-Glia Differentiation into Neurons and Glia and Their Crosstalk.

As the fifth main cell population in the brain, NG2-glia are also known as oligodendrocyte precursor cells. NG2-glia express receptors and ion channels for fast modulation of neuronal activities and signaling with neuronal synapses, which are of functional significance in both physiological and pathological states. NG2-glia also participate in fast signaling with peripheral neurons via direct synaptic contacts in the brain. These distinctive glia have the unique capability of proliferating and differentiating into oligodendrocytes, which are critical for axonal myelination in the early developing brain. In neurodegenerative diseases, NG2-glia play an important role and undergo morphological modification, adapt the expression of their membrane receptors and ion channels, and display gene-modulated cell reprogramming and excitotoxicity-caused cell death. These modifications directly and indirectly influence populations of neurons and other glial cells. NG2-glia regulate their action and dynamics in response to neuronal behavior and disease, indicating a critical function to preserve and remodel myelin in physiological states and to repair it in pathological states. Here, we review in detail the differential modulators of NG2-glia into neurons and astrocytes, as well as interactions of NG2-glia with neurons, astrocytes, and microglia. We will also summarize a future potential exploitation of NG2-glia.

Development proposals of Human Research Protection Program.

BACKGROUND: China's ethics committees alone are unable to meet the growing need for human participant protection. Several scandals in recent years indicate weaknesses in the protection of human participants in China. OBJECTIVES: The aim of the study is to summarize the status and problems of human research protection program in China and to explore its establishment proposals at national and hospital levels. RESEARCH DESIGN: To conduct literature retrieval, Chinese National Knowledge Infrastructure, Chinese Biomedical Document Database, and English databases Web of Science and PubMed were searched; laws, guidelines, and regulations were also searched on web by Google and Chinese search engine Baidu. ETHICAL CONSIDERATIONS: No data were collected from human participants, and ethical review was not required. FINDINGS: There are problems for China's Human Research Protection Program, such as weak relevant legal systems, insufficient administrative supervision, and incompetent ethics committee capacities. To fully protect human participants, China should promote the development of Human Research Protection Program, which can formulate ethics-related laws, improve regulations for the protection of the safety and rights of human participants, strengthen supervision, and enforce compensation for human participants. Owing to the frequency with which human participants are recruited in hospitals in China, hospitals can utilize existing ethics committees and establish data and safety monitoring committees, quality control, fund and contract management, and conflict of interest management offices. DISCUSSION: As a growing program, it remains necessary to learn from the experience of developed countries with high ethics standards and reformulate them to fit China's conditions to explore potential future development. The program will also be an experience for other developing countries. CONCLUSION: Human Research Protection Program can strengthen communication and coordination among various hospital departments to effectively protect the rights and welfare of human participants.

Problems and development strategies for research ethics committees in China's higher education institutions.

The establishment of research ethics committees (REC) in China's higher education institutions (HEI) is lagging far behind western developed countries. This has at least partly directly led to anomie in scientific research ethics, as seen in the recent controversies involving a proposed human head transplant and gene-edited babies. At present, the problems for REC in China's HEI include lack of regulation, informal ethics reviews, lack of supervision and insufficient ethics review capacity. To counteract these problems, suggested measures include mandatory formation of formal ethics committee, administrative support from HEI, ethics approval letter prior to funding application, formulation of regulations and standard operating procedures, selecting and training for members and independent consultants, training for secretaries and staff, ethics training for investigators, and learning from the experience of HEI outside of China, such as the USA and Canada. The establishment of REC in China's HEI will greatly enhance the overall quality of ethics reviews in China. In addition to better protecting the rights and welfare of human participants, it is also conducive to maintaining the reputation of China's HEI.

Hyperoside Alleviates High Glucose-Induced Proliferation of Mesangial Cells through the Inhibition of the ERK/CREB/miRNA-34a Signaling Pathway.

PURPOSE: Hyperoside, a flavonoid isolated from conventional medicinal herbs, has been demonstrated to exert a significant protective effect in diabetic nephropathy. This study aimed to determine the underlying mechanisms, by which hyperoside inhibits high glucose-(HG-) induced proliferation in mouse renal mesangial cells. METHODS: Mouse glomerular mesangial cells line (SV40-MES13) was used to study the inhibitory effect of hyperoside on cell proliferation induced by 30 mM glucose, which was used to simulate a diabetic condition. Viable cell count was assessed using the Cell Counting Kit-8 and by the 5-ethynyl-20-deoxyuridine incorporation assay. The underlying mechanism involving miRNA-34a was further investigated by quantitative RT-PCR and transfection with miRNA-34a agomir. The phosphorylation levels of extracellular signal-regulated kinases (ERKs) and cAMP-response element-binding protein (CREB) were measured by Western blotting. The binding region and the critical binding sites of CREB in the miRNA-34a promoter were investigated by the chromatin immunoprecipitation assay and luciferase reporter assay, respectively. RESULTS: We found that hyperoside could significantly decrease HG-induced proliferation of SV40-MES13 cells in a dose-dependent manner, without causing obvious cell death. In addition, hyperoside inhibited the activation of ERK pathway and phosphorylation of its downstream transcriptional factor CREB, as well as the miRNA-34a expression. We further confirmed that CREB-mediated regulation of miRNA-34a is dependent on the direct binding to specific sites in the promoter region of miRNA-34a. CONCLUSION: Our cumulative results suggested that hyperoside inhibits the proliferation of SV40-MES13 cells through the suppression of the ERK/CREB/miRNA-34a signaling pathway, which provides new insight to the current investigation on therapeutic strategies for diabetic nephropathy.

Omentin-1 attenuates adipose tissue inflammation via restoration of TXNIP/NLRP3 signaling in high-fat diet-induced obese mice.

Omentin-1 is an adipokine expressed by the adipose tissue and is reduced in obesity. This study was designed to calculate the protective efficiency and mechanism of omentin-1 against inflammation of the adipose tissue in obese mice. A transgenic mouse model with omentin-1 protein overexpression was established by crossing omentin-1 transgenic mice with Fabp4-Cre mice. Obesity was induced in the mice by feeding them a high-fat diet for 10 weeks. Fabp4-Cre-mediated overexpression of omentin-1 significantly increased serum omentin-1 level, serum anti-inflammatory factor levels, and expression of M2-specific mRNAs; inhibited body weight and adipose tissue weight gain; improved glucose tolerance, insulin tolerance, and insulin sensitivity; decreased serum levels of insulin and proinflammatory factors, adipocyte size, and expression of M1-specific mRNAs; suppressed macrophage infiltration; downregulated expression of proinflammatory factors; upregulated expression of anti-inflammatory factors; and inhibited thioredoxin-interacting protein (TXNIP)/NOD-like receptor 3 (NLRP3) signaling in the adipose tissue of obese mice. An NLRP3 inhibitor (20 mg/kg MCC950) exhibited the same effects as overexpression of omentin-1. Pretreatment with omentin-1 inhibited lipopolysaccharide-induced inflammation via TXNIP/NLRP3 signaling in RAW 264.7 macrophages. These findings suggest that omentin-1 suppresses adipose tissue inflammation in obese mice, at least partly, via inhibiting the TXNIP/NLRP3 signaling pathway.

Diabetic Cognitive Dysfunction: From Bench to Clinic.

Type 2 diabetes increases the risk of developing cognitive dysfunction in the elderly in the form of short-term memory and executive function impairment. Genetic and diet-induced models of type 2 diabetes further support this link, displaying deficits in working memory, learning, and memory performance. The risk factors for diabetic cognitive dysfunction include vascular disease, hypoglycaemia, hyperlipidaemia, adiposity, insulin resistance, lifestyle factors, and genetic factors. Using neuronal imaging technologies, diabetic patients with cognitive dysfunction show atrophy of the whole brain, particularly the grey matter, hippocampus and amygdala; increased volume of the ventricular and white matter; brain infarcts; impaired network integrity; abnormal microstructure; and reduced cerebral blood flow and amplitude of low-frequency fluctuations. The pathogenesis of type 2 diabetes with cognitive dysfunction involves hyperglycaemia, macrovascular and microvascular diseases, insulin resistance, inflammation, apoptosis, and disorders of neurotransmitters. Large clinical trials may offer further proof of biomarkers and risk factors for diabetic cognitive dysfunction. Advanced neuronal imaging technologies and novel disease animal models will assist in elucidating the precise pathogenesis and to provide better therapeutic interventions and treatment.

Heterogeneity and Proliferative and Differential Regulators of NG2-glia in Physiological and Pathological States.

NG2-glia, also called Oligodendrocyte Precursor Cells (OPCs), account for approximately 5%-10% of the cells in the developing and adult brain and constitute the fifth major cell population in the central nervous system. NG2-glia express receptors and ion channels involved in rapid modulation of neuronal activities and signaling with neuronal synapses, which have functional significance in both physiological and pathological states. NG2-glia participate in quick signaling with peripheral neurons via direct synaptic touches in the developing and mature central nervous system. These distinctive glia perform the unique function of proliferating and differentiating into oligodendrocytes in the early developing brain, which is critical for axon myelin formation. In response to injury, NG2-glia can proliferate, migrate to the lesions, and differentiate into oligodendrocytes to form new myelin sheaths, which wrap around damaged axons and result in functional recovery. The capacity of NG2-glia to regulate their behavior and dynamics in response to neuronal activity and disease indicate their critical role in myelin preservation and remodeling in the physiological state and in repair in the pathological state. In this review, we provide a detailed summary of the characteristics of NG2-glia, including their heterogeneity, the regulators of their proliferation, and the modulators of their differentiation into oligodendrocytes.

Neuropathy and inflammation in diabetic bone marrow.

Diabetes impairs the bone marrow (BM) architecture and function as well as the mobilization of immature cells into the bloodstream and number of potential regenerative cells. Circadian regulation of bone immature cell migration is regulated by ß-adrenergic receptors, which are expressed on haematopoietic stem cells, mesenchymal stem cells, and osteoblasts in the BM. Diabetes is associated with a substantially lower number of sympathetic nerve terminal endings in the BM; thus, diabetic neuropathy plays a critical role in BM dysfunction. Treatment with mesenchymal stem cells, BM mononuclear cells, haematopoietic stem cells, and stromal cells ameliorates the dysfunction of diabetic neuropathy, which occurs, in part, through secreted neurotrophic factors, growth factors, adipokines, and polarizing macrophage M2 cells and inhibiting inflammation. Inflammation may be a therapeutic target for BM stem cells to improve diabetic neuropathy. Given that angiogenic and neurotrophic effects are two major barriers to effective diabetic neuropathy therapy, targeting BM stem cells may provide a novel approach to develop these types of treatments.

Trigonelline inhibits caspase 3 to protect ß cells apoptosis in streptozotocin-induced type 1 diabetic mice.

As a main active ingredient of Fenugreek, trigonelline has protective efficiency on type 2 diabetes and diabetic peripheral neuropathy in rats. This study investigates the protection of trigonelline on hyperglycemia, ß cell apoptosis, and inflammation in type 1 diabetic mice. Streptozotocin (160 mg/kg) was intraperitoneal injected to induce diabetic mice. There were 4 groups: normal control, diabetes, trigonelline-treated diabetes, and insulin-treated diabetes. After 4-week treatment, levels of blood glucose, serum insulin, and inflammatory factors, ß cell apoptosis, insulin content, and oxidative stress parameters in pancreas were calculated. Pancreas was examined by immunohistochemistry staining and hematoxylin/eosin. Trigonelline significantly declined the levels of blood glucose, serum tumor necrosis factor-α, interleukin-6, and interleukin-1ß, while increased the levels of serum insulin and adiponectin in diabetic mice. Insulin content, glutathione concentration, serum activities of superoxide dismutase and catalase in pancreas, and pancreas to body weight ratio were remarkably decreased, while serum malondialdehyde concentration was increased in diabetic mice. Trigonelline treatment restored the above mentioned parameters. Trigonelline even suppresses ß cell apoptosis via downregulating caspase 3 expression. These results imply that trigonelline protects diabetic mice mediated by decreasing blood glucose, increasing insulin expression in ß cells, regulating inflammatory response, suppressing ß cells apoptosis partly by downregulating caspase 3 expression, and raising antioxidant enzyme activity.

Role of microglia-neuron interactions in diabetic encephalopathy.

In the central nervous system, the primary immune cells, the microglia, prevent pathogenic invasion as the first line of defense. Microglial energy consumption is dependent on their degree of activity. Microglia express transporters for the three primary energy substrates (glucose, fatty acids, glutamine) and regulate diabetic encephalopathy via microglia-neuron interactions. Microglia may play a sentry role for rapid protection or even ablation of impaired neurons. Neurons exhibit hyperactivity in response to hyperglycemia, hyperlipidemia, and neurotoxic factors and release potential microglial activators. Microglial activation is also regulated by proinflammatory factors, caspase-3 activity, P2X7 receptor, interferon regulatory factor-8, and glucocorticoids. Modulation of microglia in diabetic encephalopathy may involve CX3CL1, p38 MAPK, purinergic, and CD200/CD200R signaling pathways, and pattern recognition receptors. The microglia-neuron interactions play an important role in diabetic encephalopathy, and modulation of microglial activation may be a therapeutic target for diabetic encephalopathy.

Trigonelline Inhibits Inflammation and Protects ß Cells to Prevent Fetal Growth Restriction during Pregnancy in a Mouse Model of Diabetes.

BACKGROUND: As an active component from traditional Chinese medicine, trigonelline has a protective effect on diabetes. This study evaluated the protective effects of trigonelline on diabetic mice during pregnancy. METHODS: Diabetes was induced in female mice by intraperitoneal injection for continuous 5-day of 40 mg/kg/day streptozotocin. Female mice were divided into 4 groups after they were allowed to mate with normal male mice: nondiabetic, nondiabetic treated with trigonelline (70 mg/kg) for 18 days, diabetic, and diabetic treated with trigonelline (70 mg/kg). RESULTS: Diabetic pregnant mice had significantly higher levels of blood glucose, serum total cholesterol, triglyceride, insulin, and leptin but lower serum omentin-1 level and insulin sensitivity index than the nondiabetic ones. Trigonelline improved the hyperglycemia, dyslipidemia, insulin resistance, and adipocytokine of diabetic pregnant mice. Diabetic pregnant mice had significantly reduced fetus numbers, fetal weight, and fetal/placental ratio, which were reversed by trigonelline. Trigonelline prevented the increase in proinflammatory cytokines and reduced interleukin-10 level in placenta of diabetic pregnant mice. Trigonelline increased ß-cell replication and the decreased ß-cell mass, and decreased the ß-cell apoptosis of diabetic pregnant mice. CONCLUSION: These findings suggest that trigonelline protects diabetic pregnancy partly by suppressing inflammation, regulating the secretion of adipocytokines, increasing ß-cell mass, replication, and decreasing ß-cell apoptosis.

Neuroprotective effect of berberine is mediated by MAPK signaling pathway in experimental diabetic neuropathy in rats.

The mechanisms leading to diabetic neuropathy are complex. As an active component in several traditional Chinese medicines, berberine has a beneficial effect in the treatment of diabetes with hyperlipidemia. This study evaluated the protective effects of berberine on diabetic neuropathy induced by streptozotocin and a high-carbohydrate/high-fat diet in rats. Diabetic neuropathy was induced in rats by intraperitoneal injection of 35 mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Two weeks after diabetes induction, rats were treated with berberine (100 mg/kg) and rosiglitazone (4 mg/kg) for 24 weeks. Rats were studied using evoked potentials, the Morris water maze, transmission electron microscopy, real-time PCR, and Western blotting. Blood glucose, glycated hemoglobin, lipid profile, body weight, evoked potentials, and memory were altered in diabetic rats, as was the hippocampal expression of neuritin mRNA, p38 mitogen-activated protein kinase mRNA, c-Jun N-terminal kinase (JNK) mRNA, extracellular signal-regulated kinase mRNA and the phospho-proteins of p38, JNK, and extracellular signal-regulated kinase. In diabetic rats, berberine decreased body weight and the blood levels of glucose, glycated hemoglobin, triglyceride, and total cholesterol, improved memory and affected evoked potential by decreasing latency. Berberine decreased the mRNA expression of neuritin, p38, and JNK and the protein expression of neuritin, p-p38, and p-JNK. Slight micropathological changes were observed in the hippocampus of berberine-treated diabetic rats. These findings suggest that berberine has a beneficial effect against diabetic neuropathy by improving micropathology and increasing neuritin expression via the mitogen-activated protein kinase signaling pathway.

Effectiveness of problem-based learning in Chinese pharmacy education: a meta-analysis.

BACKGROUND: This review provides a critical overview of problem-based learning (PBL) practices in Chinese pharmacy education. PBL has yet to be widely applied in pharmaceutical education in China. The results of those studies that have been conducted are published in Chinese and thus may not be easily accessible to international researchers. Therefore, this meta-analysis was carried out to review the effectiveness of PBL. METHODS: Databases were searched for studies in accordance with the inclusion criteria. Two reviewers independently performed the study identification and data extraction. A meta-analysis was conducted using Revman 5.3 software. RESULTS: Sixteen randomized controlled trials were included. The meta-analysis revealed that PBL had a positive association with higher theoretical scores (SMD = 1.17, 95% CI [0.77, 11.57], P < 0.00001). The questionnaire results show that PBL methods are superior to conventional teaching methods in improving students' learning interest, independent analysis skills, scope of knowledge, self-study, team spirit, and oral expression. CONCLUSIONS: This meta-analysis indicates that PBL pedagogy is superior to traditional lecture-based teaching in Chinese pharmacy education. PBL methods could be an optional, supplementary method of pharmaceutical teaching in China. However, Chinese pharmacy colleges and universities should revise PBL curricula according to their own needs, which would maximize the effectiveness of PBL.