Selenium Yeast Alleviates Dextran Sulfate Sodium-Induced Chronic Colitis in Mice by Reducing Proinflammatory Cytokines and Regulating the Gut Microbiota and Their Metabolites.

Background: Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal inflammatory disease. Selenium has been reported to have therapeutic potential in IBD. Selenium yeast is a common selenium supplement that is convenient to access. This study explored the effect of selenium yeast on dextran sulfate sodium- (DSS-)induced chronic colitis in mice. Methods: Mice were randomly divided into four groups: the control group, selenium yeast group, chronic colitis group, and chronic colitis+selenium yeast group (n=6). Mice were killed on the 26th day. The disease activity index (DAI) score and histological damage score were calculated. Cytokines, serum selenium, colonic tissue selenium, gut microbiota and their metabolites short-chain fatty acids (SCFAs) were evaluated. Results: Selenium yeast lowered IL-1ß, IL-6, TNF-α, IL-17A, IL-22 and IFN-γ (P<0.05). In addition, selenium yeast significantly elevated Turicibacter, Bifidobacterium, Allobaculum, Prevotella, Halomonas, Adlercreutzia (P<0.05), and butyric acid (P<0.05). Conclusion: Selenium yeast could improve DSS-induced chronic colitis in mice by regulating cytokines, gut microbiota and their metabolites.

Brusatol's anticancer activity and its molecular mechanism: a research update.

OBJECTIVE: Brusatol (BT) is a quassinoid compound extracted from Brucea javanica that is a traditional Chinese herbal medicine. Brusatol possesses biological and medical activity, including antitumor, antileukemia, anti-inflammatory, antitrypanosomal, antimalarial, and antitobacco mosaic virus activity. To summarize and discuss the antitumor effects of BT and its mechanisms of actions, we compiled this review by combining the extensive relevant literature and our previous studies. METHODS: We searched and retrieved the papers that reported the pharmacological effects of BT and the mechanism of BT antitumor activity from PubMed until July 2023. KEY FINDINGS: Numerous studies have shown that BT is a unique nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor that acts on various signaling pathways and has good antitumor properties. Brusatol shows great potential in cancer therapy by inhibiting cell proliferation, blocking the cell cycle, promoting tumor cell differentiation, accelerating tumor cell apoptosis, inducing autophagy, suppressing angiogenesis, inhibiting tumor invasion and metastasis, and reversing multidrug resistance. CONCLUSION: This review summarizes recent updates on the antitumor activity and molecular mechanisms of BT and provides references for future development and clinical translation of BT and its derivatives as antitumor drugs.

Tuning Shortwave-Infrared J-aggregates of Aromatic Ring-Fused Aza-BODIPYs by Peripheral Substituents for Combined Photothermal and Photodynamic Therapies at Ultralow Laser Power.

Achieving photothermal therapy (PTT) at ultralow laser power density is crucial for minimizing photo-damage and allowing for higher maximum permissible skin exposure. However, this requires photothermal agents to possess not just superior photothermal conversion efficiency (PCE), but also exceptional near-infrared (NIR) absorptivity. J-aggregates, exhibit a significant redshift and narrower absorption peak with a higher extinction coefficient. Nevertheless, achieving predictable J-aggregates through molecular design remains a challenge. In this study, we successfully induced desirable J-aggregation (λabs max : 968 nm, ϵ: 2.96×105  M-1 cm-1 , λem max : 972 nm, ΦFL : 6.2 %) by tuning electrostatic interactions between π-conjugated molecular planes through manipulating molecular surface electrostatic potential of aromatic ring-fused aza-BODIPY dyes. Notably, by controlling the preparation method for encapsulating dyes into F-127 polymer, we were able to selectively generate H-/J-aggregates, respectively. Furthermore, the J-aggregates exhibited two controllable morphologies: nanospheres and nanowires. Importantly, the shortwave-infrared J-aggregated nanoparticles with impressive PCE of 72.9 % effectively destroyed cancer cells and mice-tumors at an ultralow power density of 0.27 W cm-2 (915 nm). This phototherapeutic nano-platform, which generates predictable J-aggregation behavior, and can controllably form J-/H-aggregates and selectable J-aggregate morphology, is a valuable paradigm for developing photothermal agents for tumor-treatment at ultralow laser power density.

Phytochemical Profile of Alkaloid Extract from Dendrobium huoshanense and Inhibitory Effects against Oxidative Stress in H2 O2 -Induced PC12 Cells.

This study aimed to explore the alkaloid profile of Dendrobium huoshanense and determine the potential protective effect against oxidative damage. The crude D. huoshanense alkaloid extract (DHAE) was obtained by 70 % ethanol extraction and liquid-liquid partition. DHAE contained specific alkaloid components with abundant 6-hydroxynobiline (58.15 %) and trace dendrobine (3.23 %) in the preliminary HPLC fingerprint and GC-MS analysis, which was distinguished from D. officinale or D. nobile. Subsequently, six alkaloids including 6-hydroxynobiline, 2-hydroxy dendrobine, nobilonine, dendrobine, Findlayines D and trans-dendrochrysanine were identified in the purified DHAE (namely DHSAE-3, DHSAE-3') via further solid phase extraction coupled with UPLC-MS/MS analysis. Meanwhile, pretreatment with DHAE or DHSAE (0.5, 5 µg/mL) increased cell viability by 14.0-57.4 % compared to that of H2 O2 -induced PC12 Model cells. Among them, 5 µg/mL DHSAE-3-treated cells displayed a pronounced reversion than the positive vitamin E (p<0.01). Furthermore, a clear cellular morphological restoration and 38.4 % reduction in intracellular reactive oxidative species level were achieved. Our findings suggest that D. huoshanense has a characteristic alkaloid profile represented by abundant 6-hydroxynobiline, and DHAEs exhibit obvious protection against oxidative neuronal damage. Overall, this study indicates that DHAEs might be used to inhibit oxidative stress and provide a source to develop novel neuroprotective drugs.

A comparative study of pectic polysaccharides from fresh and dried Dendrobium officinale based on their structural properties and hepatoprotection in alcoholic liver damaged mice.

In this study, two pectic polysaccharides from fresh and dried Dendrobium officinale, namely FDP and DDP, were obtained by sour-water extraction, ethanol precipitation and further purification with DEAE cellulose-52 and Sephadex G-100 column chromatography. FDP/DDP had eight similar glycosidic linkages including 1,4-linked-GlcAp, 1,4- and 1,3,4-linked-GalAp, 1,3,4- and T-linked-Glcp, 1,6- and T-linked-Galp, T-linked-Galp and T-linked-Xylp. Besides, FDP was marked by 1,6-, 1,2,6-linked-Manp and 1,2,4-, 1,2-linked-Rhap, and DDP consisted of unique 1,6-linked-GlcAp and 1,3,6-Manp. FDP with a molecular weight of 14.8 kDa generally showed stronger scavenging capacity against DPPH, ABTS and hydroxyl radicals than DDP (p < 0.05). Pretreatment with FDP/DDP alleviated the alcohol-induced liver injury in mice, and their serum aminotransferase and triglyceride levels were 10.3%-57.8% lower than those of the model group (MG). Meanwhile, the FDP/DDP-M and FDP/DDP-H groups (200 and 300 mg kg-1) displayed a remarkable increase in antioxidant enzyme activities and significant reduction in inflammatory cytokine levels in comparison with the MG. Further analysis revealed that FDP-treated mice generally exhibited lower transaminase levels and inflammatory cytokine expression as well as higher antioxidant enzyme activities than DDP-treated ones. The FDP-H group showed significant restoration, which was slightly less than or almost comparable to that of the bifendate-fed positive control. The above results indicate that D. officinale pectin can attenuate oxidative stress and inflammatory cytokine response, and ultimately ameliorate liver injury, and "fresh" pectin with specific structural characteristics is expected to be more promising as hepatoprotective food.

Network pharmacology combined with GEO database identifying the mechanisms and molecular targets of Polygoni Cuspidati Rhizoma on Peri-implants.

Peri-implants is a chronic disease leads to the bone resorption and loss of implants. Polygoni Cuspidati Rhizoma (PCRER), a traditional Chinese herbal has been used to treat diseases of bone metabolism. However, its mechanism of anti-bone absorption still remains unknown. We aimed to identify its molecular target and the mechanism involved in PCRER potential treatment theory to Peri-implants by network pharmacology. The active ingredients of PCRER and potential disease-related targets were retrieved from TCMSP, Swiss Target Prediction, SEA databases and then combined with the Peri-implants disease differential genes obtained in the GEO microarray database. The crossed genes were used to protein-protein interaction (PPI) construction and Gene Ontology (GO) and KEGG enrichment analysis. Using STRING database and Cytoscape plug-in to build protein interaction network and screen the hub genes and verified through molecular docking by AutoDock vina software. A total of 13 active compounds and 90 cross targets of PCRER were selected for analysis. The GO and KEGG enrichment analysis indicated that the anti-Peri-implants targets of PCRER mainly play a role in the response in IL-17 signaling, Calcium signaling pathway, Toll-like receptor signaling pathway, TNF signaling pathway among others. And CytoHubba screened ten hub genes (MMP9, IL6, MPO, IL1B, SELL, IFNG, CXCL8, CXCL2, PTPRC, PECAM1). Finally, the molecular docking results indicated the good binding ability with active compounds and hub genes. PCRER's core components are expected to be effective drugs to treat Peri-implants by anti-inflammation, promotes bone metabolism. Our study provides new thoughts into the development of natural medicine for the prevention and treatment of Peri-implants.

Exploring the pharmacological components and effective mechanism of Mori Folium against periodontitis using network pharmacology and molecular docking.

OBJECTIVES: To investigate the main active components, potential targets of action and analyze the potential molecular mechanisms of Mori Folium in preventing and treating periodontitis using network pharmacology and molecular docking methods. MATERIALS AND METHODS: The main components and action targets of Mori Folium were obtained in TCMSP and ETCM databases, and then the action targets of Mori Folium components were inversing screening using Swiss Target Prediction and BATMAN-TCM databases. Targets associated with periodontitis were retrieved from OMIM, Genecard, DrugBank, NCBI Gene and DisGeNET databases. Intersectional targets of Mori Folium and periodontitis were obtained by Venn analysis. Construction of an "active components-targets" network to prevent and treat periodontitis in Mori Folium using Cytoscape 3.8.0. The STRING database was used to construct the protein-protein interaction (PPI) network of intersecting targets, and the core network was screened using CytoNCA and MCODE plug-ins. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed using the ClusterProfile package of R software, and then the "Mori Folium active components-targets-signaling pathway" network was constructed using Cytoscape software. Molecular docking was performed using AutoDock Vina software, and Pymol and LigPlus visualized the results. RESULTS: Sixteen active components and 1048 targets were screened from Mori Folium, of which 164 were intersectional with periodontitis targets and were considered potential therapeutic targets. The "Mori Folium active components-action targets" network identified Quercetin, Moracin D, Moracin E, Moracin G, Moracin H and Moracin B as the main active ingredients of Mori Folium for the prevention and treatment of periodontitis. PPI network analysis revealed interleukin 6 (IL6), albumin (ALB), tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), RAC-alpha serine/threonine-protein kinase (AKT1), cellular tumor antigen p53 (TP53), prostaglandin G/H synthase 2 (PTGS2), pro-epidermal growth factor (EGF), matrix metalloproteinase 9 (MMP9) and interleukin 6 (IL10) as the top 10 core potential targets. GO and KEGG enrichment analyses showed that the action targets of Mori Folium against periodontitis were mainly related to the response to bacterium and their lipopolysaccharide, angiogenesis and reactive oxygen species metabolic process, as well as through signaling pathways that regulate processes related to the accumulation of advanced glycation end products (AGEs), response to oxidative stress, response to inflammatory, and osteoclast differentiation during the development of the disease. Molecular docking revealed that Quercetin, Moracin D, Moracin E, Moracin G, Moracin H and Moracin B were able to bind stably to AKT1, PTGS2 and ESR1 targets, with Moracin E showing the most stable structure after binding to AKT1. CONCLUSIONS: In conclusion, this study revealed the active components, potential targets of action and the potential molecular mechanisms and pharmacological activities involved in the prevention and treatment of periodontitis in Mori Folium, providing a reference for the development of drugs from Mori Folium for the prevention and treatment of periodontitis.

Soybean Oil Treatment Using the Dissolving Curve Equation of Hydrogen.

The solubility of hydrogen in n-hexane was determined using a homemade reactor. The solubility of hydrogen in soybean oil was established using the Peng-Robinson (PR) equation of state and the van der Waals mixing rule. The curve equation established a linear relationship between the solubility of hydrogen in oil and the number of moles of hydrogen in the reactor. Under the optimal temperature and catalyst, the relationship between the hydrogen consumption of the hydrogenation of oil and fat and the TFAs formed in the oil was determined. When the reaction pressure exceeded 3.0 MPa, the hydrogenation of oil was consumed. The amount of hydrogen, the rate of hydrogenation, and the change in the TFAs all stabilized. Therefore, the pressure of the general hydrogenation reaction should not exceed 3.0 MPa. This result provides a quick and simple method for controlling TFAs in oils and fats for industrial applications.

Preparation, characterization, antioxidant and anti-inflammatory activities of acid-soluble pectin from okra (Abelmoschus esculentus L.).

Currently, there are few studies on acid-soluble pectin from okra, especially in biological activity for antioxidant and anti-inflammatory. In this study, the antioxidant properties of acid-soluble okra pectin components and their anti-inflammatory were explored. Firstly, two acid-soluble okra pectic fractions, namely crude acid-soluble okra pectin (CAOP) and acid-soluble okra pectin (AOP), were obtained and exhibited structural and compositional variation. The two pectic fractions contained a low degree of esterification (42.0-46.5%) and a relatively high uronic acid content (31.6-37.3%). AOP was composed of galacturonic acid (79.1 mol/%), galactose (4.3 mol/%), rhamnose (14.5 mol/%) and xylose (2.1 mol/%), and the molecular weight was 92.8 kDa. Morphological and thermal properties of acid-soluble okra pectin components were also investigated. Compared to CAOP, AOP expressed better antioxidant activity, and suppressed the NO production in LPS-induced RAW 264.7 macrophages. All the above results indicated that AOP had the potential to act as a natural antioxidant or a functional anti-inflammatory food, which would broaden the development and utilization of okra resources.

Okra pectin relieves inflammatory response and protects damaged intestinal barrier in caerulein-induced acute pancreatic model.

BACKGROUND: Protecting the intestinal mucosa from being destroyed helps reduce the inflammation caused by acute pancreatitis (AP). In this study, whether okra pectin (OP) could attenuate the inflammation of AP through protecting the intestinal barrier was investigated. RESULTS: OP was obtained from crude okra pectin (COP) through the purification by DEAE cellulose 52 column. Supplementation with OP or COP in advance reduced the severity of AP, as revealed by lower serum amylase and lipase levels, abated pancreatic edema, attenuated myeloperoxidase activity and pancreas histology. OP or COP inhibited the production of pancreatic proinflammatory cytokines, including tumor necrosis factor-α and interleukin-6. In addition, the upregulation of AP-related proteins including ZO-1, occludin, the antibacterial peptide-defensin-1 (DEFB1) and cathelicidin-related antimicrobial peptide (CRAMP), as well as the histological examination of colon injuries, demonstrated that OP or COP provision could effectively maintain intestinal barrier function. Ultimately, dietary OP or COP supplementation could inhibit AP-induced intestinal inflammation. For the above, the effect of OP was better than COP. CONCLUSION: Dietary OP supplementation could be considered as a preventive method that effectively interferes with intestinal damage and attenuates inflammatory responses trigged by AP. © 2020 Society of Chemical Industry.

Prediction of the pharmacological characteristics and therapeutic mechanism of Tripterygium wilfordii in treating oral lichen planus based on network pharmacology / 口腔疾病防治

Objective@#To explore the potential mechanism of the main active component Tripterygium wilfordii in the treatment of oral lichen planus based on network pharmacology.@*Methods@#The components of Tripterygium wilfordii and targets were searched through the Traditional Chinese Medicine system pharmacology database and analysis platform (TCMSP) and the Traditional Chinese Medicine integrated database (TCMID) databases. The related targets of oral lichen planus (OLP) were obtained through databases such as Gene Cards. The OLP targets were mapped by Venn analysis to the targets of Tripterygium wilfordii to screen out the common targets as the treatment of OLP targets of Tripterygium wilfordii. The Cytoscape software and STRING were used to construct a chemical component-target network and protein-protein interaction network, a network analyzer was used to compute the network topology properties, a cluster profiler software was used to analyze the GO classification enrichment analysis and KEGG signal path analysis, and a Tripterygium wilfordii chemical components-targets-pathway network diagram was constructed. @*Results@#Twenty-three components and 44 OLP treatmenttargets of Tripterygium wilfordii were obtained. The key active ingredients of Tripterygium wilfordii in the treatment of OLP are triptolide, kaempferol, and tangerine peel. The key targets include TNF and AKT1. The GO classification enrichment analysis obtained 63 GO terms, which are mainly involved in the leukocyte differentiation and reaction to lipopolysaccharides. The KEGG analysis identified 111 signaling pathways, which are mainly related to the TNF signaling pathway and IL17 signaling pathway. @*Conclusion@#Tripterygium wilfordii in the treatment of OLP. This study can provide a theoretical basis for further research to explore drugs with high activity and low toxicity to treat OLP from Tripterygium wilfordii.

Effect of pH regulation on the components and functional properties of proteins isolated from cold-pressed rapeseed meal through alkaline extraction and acid precipitation.

Cold-pressed rapeseed meal with high protein content (38.76% protein dry weight basis) was used to prepare rapeseed protein isolates (RPIs) by alkaline extraction (pH 8.0, 9.0, 10.0, 11.0, 12.0 and 13.0) and acid precipitation (pH 3.0, 3.5, 4.0, 4.5, 5.0 and 5.5). The protein with an intact structure and the highest yield (65.08%) was obtained at extraction pH 9.0 and precipitation pH 4.5, accompanied by the lowest D-amino acid content, the lightest colour and the lowest contents of glucosinolates (2.85 mmol/kg), phytic acid (1.05 mg/g) and sinapine (0.68 mg/g). Additionally, water/oil absorption, foaming and emulsifying capacities decreased with decreasing precipitation pH, while the solubility showed the reverse trend. During gastric simulation digestion, the α-polypeptide of cruciferin and napin in the RPIs showed digestive resistance. Overall, pH regulation might be an effective method to isolate high quality RPIs for use in the food processing industry.

Two macamide extracts relieve physical fatigue by attenuating muscle damage in mice.

BACKGROUND: Macamides, the main active components contained in maca, have attracted increasing attention due to their various bioactivities. In this study, crude macamide extract (CME) and purified macamide extract (PME) were prepared by enzyme-assisted extraction and macroporous resin separation, and the anti-fatigue effects of CME and PME were evaluated in a forced swimming model. RESULTS: The composition analysis results revealed that both CME and PME mainly contain eight kinds of macamide. Based on the results of a weight-loaded forced swimming test, compared with a control group, CME and and PME groups could prolong exhaustive swimming time, increase levels of liver glycogen (LG) and muscle glycogen (MG), accelerate fatty acid oxidation in serum to provide energy, eliminate the accumulation of blood lactic acid (BLA) and blood urea nitrogen (BUN), and decrease the serum biomarkers for muscle damage, such as lactate dehydrogenase (LDH) and creatine kinase (CK). Histological analysis also indicated that CME and PME attenuated damage to skeletal muscle and the myocardium in mice during exercise. CONCLUSION: Two macamide extracts have a beneficial effect on relieving physical fatigue by attenuating the damage of skeletal muscle and myocardium during exercise, and a better effect was observed in the PME group. © 2018 Society of Chemical Industry.

Optimization on conditions of podophyllotoxin-loaded liposomes using response surface methodology and its activity on PC3 cells.

The purpose of this study was to optimize the preparation conditions of podophyllotoxin liposomes (PPT-Lips), and to investigate their effects on PC3 cells. PPT-Lips were prepared by using a thin-film dispersion method. In order to achieve maximum drug encapsulation efficiency (EE), the process and formulation variables were optimized by response surface methodology (RSM). The optimum preparation conditions were cholesterol to lecithin ratio of 3.6:40 (w/w), lipid to drug ratio of 15.8:1 (w/w), and the ultrasonic intensity of 35% (total power of 400 W). The experimental EE of PPT-Lips was 90.425%, which was consistent with the theoretically predicted value. The characterization studies showed that PPT-Lips were well-dispersible spherical particles with an average size of 106 nm and a zeta potential of -10.1 mV. A gradual and time-dependent pattern of PPT from liposomes was found in in vitro drug release with a cumulative release amount up to 70.3% in 24 h. Results of cell viability experiments on PC3 cells demonstrated that PPT-Lips exhibited more effective anticancer activity in comparison with free PPT. Therefore, PPT-Lips represent an efficient and promising drug delivery system for PPT.

Purification, characterization and anti-fatigue activity of polysaccharide fractions from okra (Abelmoschus esculentus (L.) Moench).

The aim of this study was to investigate the anti-fatigue activity of polysaccharide fractions from Abelmoschus esculentus (L.) Moench (AE) in mice. After crude polysaccharide (CAEP) was extracted from AE and purified by DEAE cellulose-52 column, two polysaccharide fractions (AEP-1 and AEP-2) were obtained. The structural analysis suggested that AEP-1 and AEP-2 were a RG-I polysaccharide and an AG-II polysaccharide, respectively. According to the results of the weight-loaded swimming test, compared with the negative control group, the CAEP, AEP-1 and AEP-2 treatment groups could prolong the swimming time, decrease serum urea nitrogen (SUN) and blood lactic acid (BLA), and increase hepatic glycogen (HG) and muscle glycogen (MG), which indicated that okra polysaccharides have an effective anti-fatigue activity. Furthermore, our study exhibited the anti-fatigue mechanism of okra polysaccharide was correlated with retarding the accumulation of creatine kinase (CK) and lactate dehydrogenase (LDH) in serum, and enhancing succinate dehydrogenase (SDH), adenosine triphosphate (ATP) and adenosine triphosphatase (ATPase) levels. In addition, the anti-fatigue activity of AEP-1 was stronger than that of AEP-2, and significantly better than that of CAEP. Therefore, AEP-1 and AEP-2 may be the main active anti-fatigue functional substances of AE.

1H NMR-based metabolic study reveals the improvements of bitter melon (Momordica charantia) on energy metabolism in diet-induced obese mouse.

CONTEXT: Obesity can be ameliorated by some natural products such as polyphenol, flavones and saponin. As a typical medicinal plant, Momordica charantia L. (Cucurbitaceae) (bitter melon, BM) contains these natural chemicals and reduces diet-induced obesity in mice. OBJECTIVE: This study evaluates the metabolic effects of dietary BM supplement, investigates a global metabolic profile and determines associated perturbations in metabolic pathways. MATERIALS AND METHODS: Male C57BL/6 mice were fed with low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with 5% BM based on 37.6 g/kg body weight in average for 12 weeks, respectively. Then energy metabolism was quantified using PhenoMaster/LabMaster. The spectroscopy of urine was acquired by nuclear magnetic resonance and latent biomarkers were identified. Pattern recognition analysis was used to discriminate associated metabolic profiles. RESULTS: Dietary BM supplement reduced body weight gain (-0.15-fold, p < 0.01) and blood glucose levels (-0.19-fold, p < 0.01) in HFD-fed mice. Meanwhile, the levels of energy metabolism were enhanced (0.08-0.11-fold, p < 0.01). According to pattern recognition analysis, dietary BM supplement changed metabolic profiles in HFD-fed mice and the modified profiles were similar to those in LFD-fed mice. Finally, the mapping of metabolic pathways showed that dietary BM supplement primarily affected glucose metabolism-associated pathways. DISCUSSION AND CONCLUSION: The results indicated that BM improves weight loss in diet-induced obesity and elevate energy expenditure in HFD-fed mice. The pattern recognition with metabolic study may be used as a noninvasive detection method to assess the effects of dietary BM supplement on mouse energy metabolism.

Maternal folic acid supplementation and the risk of congenital heart defects in offspring: a meta-analysis of epidemiological observational studies.

Epidemiological studies have reported conflicting results regarding the association between maternal folic acid supplementation and the risk of congenital heart defects (CHDs). However, a meta-analysis of the association between maternal folic acid supplementation and CHDs in offspring has not been conducted. We searched the MEDLINE and EMBASE databases for articles cataloged between their inceptions and October 10, 2014 and identified relevant published studies that assessed the association between maternal folate supplementation and the risk of CHDs. Study-specific relative risk estimates were pooled using random-effects or fixed-effects models. Out of the 1,606 articles found in our initial literature searches, a total of 1 randomized controlled trial, 1 cohort study, and 16 case-control studies were included in our final meta-analysis. The overall results of this meta-analysis provide evidence that maternal folate supplementation is associated with a significantly decreased risk of CHDs (RR = 0.72, 95% CI: 0.63-0.82). Statistically significant heterogeneity was detected (Q = 82.48, P < 0.001, I(2) = 79.4%). We conducted stratified and meta-regression analyses to identify the origin of the heterogeneity among the studies, and a Galbraith plot was generated to graphically assess the sources of heterogeneity. This meta-analysis provides a robust estimate of the positive association between maternal folate supplementation and a decreased risk of CHDs.