Dynamic assessment of coronary artery during different cardiac cycle in patients with coronary artery disease using coronary CT angiography.

INTRODUCTION: To evaluate the effect of the cardiac cycle for the coronary artery opening and coronary stenosis at the plaque to determine the phase of measuring maximum diameters required for coronary artery disease (CAD). METHODS: This retrospective study assessed data for 208 consecutive patients who underwent coronary computed tomography angiography (CTA). The cross-sectional area and diameters of the opening of the left main coronary artery (LM), left anterior descending branch (LAD), left circumflex branch (LCX) and right coronary artery (RCA), the stenosis rate of involved vessels were measured in 10 cardiac cycles. And all their dynamic changes were estimated by the linear mixed model. The relationship between stenosis rate and opening orifice were analyzed by monofactorial variance. RESULTS: The opening parameters and stenosis rate of the four main coronary arteries varied within the cardiac cycle (p < .05). The maximum opening area occurred at the 45%-55% phase; The range of stenosis rate varied approximately 11%-14% and the maximum stenosis rate was at the 65% phase. The degree of vascular stenosis for LM, LAD and LCX were not associated with their corresponding opening diameters, but were positively intercorrelation with each other. CONCLUSION: For patients with CAD, the maximum coronary artery stenosis rate were at 65% phase and the maximum value of coronary artery opening were at 45%-55% phase, which were chosen for the appropriate measurement and evaluation by CTA.

Assessment of hepatic fat content and prediction of myocardial fibrosis in athletes by using proton density fat fraction sequence.

PURPOSE: To explore the characteristics of the hepatic fat content in athletes, and predict late gadolinium enhancement (LGE) based on magnetic resonance imaging-proton density fat fraction (MRI-PDFF). MATERIAL AND METHODS: From March 2020 to March 2021, 233 amateur athletes and 42 healthy sedentary controls were prospectively recruited. The liver fat content of four regions of interest (ROIs 1-4), the mean liver fat fraction (FF), cardiac function, and myocardium LGE were recorded, respectively. The values of ROIs 1-4 and FF were compared between athletes and controls. According to the liver fat content threshold for distinguishing athletes and controls, the cutoff total exercise time that induced a change in liver fat was obtained. The correlations among the liver fat content, cardiac function, and other parameters were analyzed. Moreover, the liver fat content was used to predict myocardium LGE by logistic regression. RESULTS: There were significant differences for the values of ROI 1, ROI 3, ROI 4, and FF between athletes and controls (allp< 0.05). The cutoff total exercise time for inducing a change in the liver fat content was 1680 h (area under the curve [AUC] = 0.593, specificity = 83.3,p< 0.05). Blood indexes, cardiac function, and basic clinical parameters were related to liver fat content (allp< 0.05). The prediction model for LGE had an AUC value of 0.829 for the receiver operator characteristic curve. CONCLUSION: MRI-PDFF could assess liver fat content and predict cardiac fibrosis in athletes for risk stratification and follow-up.

Combination of Lycopene and Curcumin Synergistically Alleviates Testosterone-Propionate-Induced Benign Prostatic Hyperplasia in Sprague Dawley Rats via Modulating Inflammation and Proliferation.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH. METHOD: To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH. RESULTS: Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer. CONCLUSION: The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.

Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis.

BACKGROUND: Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown. METHODS: The expressions of TUG1, microRNA-216b-5p and distal-less homeobox 2 (DLX2) were detected by Quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships were predicted by StarBase v.2.0 or TargetScan and confirmed by dual-luciferase reporter assay. The cell growth, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow cytometry and Transwell assays, respectively. All protein expression levels were detected by western blot. Tumor xenografts were implemented to explore the role of TUG1 in vivo. RESULTS: We found that there was a marked rise in TUG1 expression in HCC tissues and cells, and knockdown of TUG1 repressed the growth and metastasis and promoted apoptosis of HCC cells. In particular, TUG1 could act as a ceRNA, effectively becoming a sink for miR-216b-5p to fortify the expression of DLX2. Additionally, repression of TUG1 impared the progression of HCC cells by inhibiting DLX2 expression via sponging miR-216b-5p in vitro. More importantly, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-216b-5p via inactivation of the DLX2. CONCLUSION: TUG1 interacting with miR-216b-5p contributed to proliferation, metastasis, tumorigenesis and retarded apoptosis by activation of DLX2 in HCC.

Traditional Chinese medicine as targeted treatment for epithelial-mesenchymal transition-induced cancer progression.

The epithelial-mesenchymal transition (EMT) program, which loosens cell-cell adhesion complexes, endows cells with enhanced migratory and invasive properties. Furthermore, this process facilitates both the development of drug resistance and immunosuppression by tumor cells, which preclude the successful treatment of cancer. Recent research has demonstrated that many signaling pathways are involved in EMT progression. In addition, cancer stem cells (CSCs), vasculogenic mimicry (VM) and the tumor-related immune microenvironment all play important roles in tumor formation. However, there are few reports on the relationships between EMT and these factors. In addition, in recent years, traditional Chinese medicine (TCM) has developed a unique system for treating cancer. In this review, we summarize the crucial signaling pathways associated with the EMT process in cancer patients and discuss the interconnections between EMT and other molecular factors (such as CSCs, VM, and the tumor-related immune microenvironment). We attempt to identify common regulators that might be potential therapeutic targets to thereby optimize tumor treatment. In addition, we outline recent research on TCM approaches that target EMT and thereby provide a foundation for further research on the exact mechanisms by which TCMs affect EMT in cancer.

Aberrant transcriptomes and DNA methylomes define pathways that drive pathogenesis and loss of brain laterality/asymmetry in schizophrenia and bipolar disorder.

Although the loss of brain laterality is one of the most consistent modalities in schizophrenia (SCZ) and bipolar disorder (BD), its molecular basis remains elusive. Our limited previous studies indicated that epigenetic modifications are key to the asymmetric transcriptomes of brain hemispheres. We used whole-genome expression microarrays to profile postmortem brain samples from subjects with SCZ, psychotic BD [BD[+]] or non-psychotic BD [BD(-)], or matched controls (10/group) and performed whole-genome DNA methylation (DNAM) profiling of the same samples (3-4/group) to identify pathways associated with SCZ or BD[+] and genes/sites susceptible to epigenetic regulation. qRT-PCR and quantitative DNAM analysis were employed to validate findings in larger sample sets (35/group). Gene Set Enrichment Analysis (GSEA) demonstrated that BMP signaling and astrocyte and cerebral cortex development are significantly (FDR q < 0.25) coordinately upregulated in both SCZ and BD[+], and glutamate signaling and TGFß signaling are significantly coordinately upregulated in SCZ. GSEA also indicated that collagens are downregulated in right versus left brain of controls, but not in SCZ or BD[+] patients. Ingenuity Pathway Analysis predicted that TGFB2 is an upstream regulator of these genes (p = .0012). While lateralized expression of TGFB2 in controls (p = .017) is associated with a corresponding change in DNAM (p ≤ .023), lateralized expression and DNAM of TGFB2 are absent in SCZ or BD. Loss of brain laterality in SCZ and BD corresponds to aberrant epigenetic regulation of TGFB2 and changes in TGFß signaling, indicating potential avenues for disease prevention/treatment.

Diet phytochemicals and cutaneous carcinoma chemoprevention: A review.

Cutaneous carcinoma, which has occupied a peculiar place among worldwide populations, is commonly responsible for the considerably increasing morbidity and mortality rates. Currently available medical procedures fail to completely avoid cutaneous carcinoma development or to prevent mortality. Cancer chemoprevention, as an alternative strategy, is being considered to reduce the incidence and burden of cancers through chemical agents. Derived from dietary foods, phytochemicals have become safe and reliable compounds for the chemoprevention of cutaneous carcinoma by relieving multiple pathological processes, including oxidative damage, epigenetic alteration, chronic inflammation, angiogenesis, etc. In this review, we presented comprehensive knowledges, main molecular mechanisms for the initiation and development of cutaneous carcinoma as well as effects of various diet phytochemicals on chemoprevention.

Microbiome, inflammation, epigenetic alterations, and mental diseases.

Major mental diseases such as autism, bipolar disorder, schizophrenia, and major depressive disorder are debilitating illnesses with complex etiologies. Recent findings show that the onset and development of these illnesses cannot be well described by the one-gene; one-disease approach. Instead, their clinical presentation is thought to result from the regulative interplay of a large number of genes. Even though the involvement of many genes are likely, up regulating and activation or down regulation and silencing of these genes by the environmental factors play a crucial role in contributing to their pathogenesis. Much of this interplay may be moderated by epigenetic changes. Similar to genetic mutations, epigenetic modifications such as DNA methylation, histone modifications, and RNA interference can influence gene expression and therefore may cause behavioral and neuronal changes observed in mental disorders. Environmental factors such as diet, gut microbiota, and infections have significant role in these epigenetic modifications. Studies show that bioactive nutrients and gut microbiota can alter either DNA methylation and histone signatures through a variety of mechanisms. Indeed, microbes within the human gut may play a significant role in the regulation of various elements of "gut-brain axis," via their influence on inflammatory cytokines and production of antimicrobial peptides that affect the epigenome through their involvement in generating short chain fatty acids, vitamin synthesis, and nutrient absorption. In addition, they may participate in-gut production of many common neurotransmitters. In this review we will consider the potential interactions of diet, gastrointestinal microbiome, inflammation, and epigenetic alterations in psychiatric disorders.

IGF2BP3 loss inhibits cell progression by upregulating has_circRNA_103820, and hsa_circRNA_103820-encoded peptide inhibits cell progression by inactivating the AKT pathway in lung cancer.

N6-methyladenosine (m6A) modification and m6A-related RNA-binding proteins (RBPs) play vital roles in various aspects of circRNA metabolism. Hsa_circRNA_103820 is implicated in the pathogenesis of multiple cancers, including lung cancer (LC). Moreover, bioinformatics analysis has suggested that hsa_circRNA_103820 possesses potential peptide-coding ability. Thus, we aimed to investigate the function and peptide-coding potential of hsa_circRNA_103820 in this study. Cell viability, apoptosis rate, and migratory and invasive abilities were assessed using CCK-8, flow cytometry, and transwell assays, respectively. Hsa_circRNA_103820 level was measured using RT-qPCR assay, and the interaction between hsa_circRNA_103820 and IGF2BP3 was examined through RIP and RT-qPCR assays. The coding ability of hsa_circRNA_103820 and protein levels were determined through western blot assay. The results showed that hsa_circRNA_103820 reduced cell viability, attenuated cell migratory and invasive abilities, and promoted cell apoptosis in LC. IGF2BP3 negatively regulated hsa_circRNA_103820 expression and interacted with it. Hsa_circRNA_103820 knockdown alleviated si-IGF2BP3-mediated anti-viability, anti-migration, anti-invasion, and pro-apoptosis effects in LC cells. Moreover, a 188-amino acid (aa) peptide encoded by hsa_circRNA_103820 decreased cell viability, facilitated cell apoptosis, and inhibited cell migration and invasion in LC. Collectively, hsa_circRNA_103820, regulated by IGF2BP3, encodes a 188-aa peptide and inhibits the malignant progression of LC cells by inhibiting the AKT pathway.

Gut microbiota defined epigenomes of Alzheimer's and Parkinson's diseases reveal novel targets for therapy.

The origins of Alzheimer's disease (AD) and Parkinson's disease (PD) involve genetic mutations, epigenetic changes, neurotoxin exposure and gut microbiota dysregulation. The gut microbiota's dynamic composition and its metabolites influence intestinal and blood-brain barrier integrity, contributing to AD and PD development. This review explores protein misfolding, aggregation and epigenetic links in AD and PD pathogenesis. It also highlights the role of a leaky gut and the microbiota-gut-brain axis in promoting these diseases through inflammation-induced epigenetic alterations. In addition, we investigate the potential of diet, probiotics and microbiota transplantation for preventing and treating AD and PD via epigenetic modifications, along with a discussion related to current challenges and future considerations. These approaches offer promise for translating research findings into practical clinical applications.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common age-related brain diseases. The incidence of AD is almost 20% in individuals over the age of 80 years, and the incidence of PD is 1­4% in individuals over the age of 60 years. Research scientists are studying various links among key factors involved in AD and PD pathogenesis, including diet, gut microbiota (communal bacteria living in our gut), neuroinflammation, epigenetic modifications (regulation of gene expression that is affected by environmental factors) and genetic changes to obtain greater insights into the mechanisms of disease development to design better therapeutics for these disabling diseases. The discovery of these relationships will provide opportunities to maintain favorable health via diet­microbiota­epigenetic modifications, since diet and surrounding environments play crucial roles in gut microbial alterations. Here, we discuss the interactions between destructive protein misfolding/aggregation in AD and PD, with neuroinflammation and epigenetic alterations that all are affected by nutrition, microbiota dysbiosis (imbalance), leaky gut (gut­blood barrier disruption) and internal or environmental toxins. We also present thought-provoking discussions and ideas about recent preventive/therapeutic approaches like special diets, probiotics, fecal microbiota transplantation and even specific antibiotics for preventing or improving neuropsychiatric symptoms in AD and PD.

Choosing the Adaptive Cardiac Phase for Assessing Cardiac Dimensions Using Cardiac Computed Tomography for Heart Disease.

Background: Cardiac chamber dimensions and left ventricle (LV) wall thickness change with the cardiac cycle, in which researchers have set different time points for systole and diastole. OBJECTIVE: This study aimed to provide characteristics of normal heart and choose the correct cardiac cycle to measure maximum cardiac parameters for cardiovascular disease. METHODS: The parameters of left atrium (LA), LV, right atrium (RA), and right ventricle (RV), as well as the wall thickness of LV, were measured in different cardiac phases using cardiac computed tomography (CT). Then, their differences in different phases and the correlation between these parameters and traditional risk factors were analyzed. In addition, receiver operator characteristic curve (ROC) analyses was performed to estimate LA enlargement. RESULTS: The dimensions of LA and RA as well as the wall thickness of LV reached the maximum at the phase of 35% - 45%, while the dimensions of LV and RV reached the maximum at 95% - 5%. However, the changes of LA-B (antero-posterior diameter), LV-D1 (basal dimension), RA-B (minor dimension), and RV-D2 (mid cavity dimension) were relatively more stable than other diameters during the cardiac cycle. The maximum LA-B diameter, LV-D1 diameter, RA-B diameter, and RV-D2 diameter as well as the maximum interventricular septum thickness were acquired. Heart rate (HR) and smoking were potential indicators of LV-D2 (mid cavity dimension), while HR and LV myocardial mass were potential indicators of LV-D3 (apical-basal dimension). In phase 45%, the cut-off value of LA-B was 37.12 mm, with high sensitivity for predicting LA enlargement. CONCLUSION: Choosing the adaptive cardiac phase for evaluating cardiac chamber dimensions and wall thickness obtained by cardiac CT could provide a more accurate clinical measurement of the heart.

iPSC-Derived Astrocytes and Neurons Replicate Brain Gene Expression, Epigenetic, Cell Morphology and Connectivity Alterations Found in Autism.

Excessive inflammatory reactions and oxidative stress are well-recognized molecular findings in autism and these processes can affect or be affected by the epigenetic landscape. Nonetheless, adequate therapeutics are unavailable, as patient-specific brain molecular markers for individualized therapies remain challenging. METHODS: We used iPSC-derived neurons and astrocytes of patients with autism vs. controls (5/group) to examine whether they replicate the postmortem brain expression/epigenetic alterations of autism. Additionally, DNA methylation of 10 postmortem brain samples (5/group) was analyzed for genes affected in PSC-derived cells. RESULTS: We found hyperexpression of TGFB1, TGFB2, IL6 and IFI16 and decreased expression of HAP1, SIRT1, NURR1, RELN, GPX1, EN2, SLC1A2 and SLC1A3 in the astrocytes of patients with autism, along with DNA hypomethylation of TGFB2, IL6, TNFA and EN2 gene promoters and a decrease in HAP1 promoter 5-hydroxymethylation in the astrocytes of patients with autism. In neurons, HAP1 and IL6 expression trended alike. While HAP1 promoter was hypermethylated in neurons, IFI16 and SLC1A3 promoters were hypomethylated and TGFB2 exhibited increased promoter 5-hydroxymethlation. We also found a reduction in neuronal arborization, spine size, growth rate, and migration, but increased astrocyte size and a reduced growth rate in autism. In postmortem brain samples, we found DNA hypomethylation of TGFB2 and IFI16 promoter regions, but DNA hypermethylation of HAP1 and SLC1A2 promoters in autism. CONCLUSION: Autism-associated expression/epigenetic alterations in iPSC-derived cells replicated those reported in the literature, making them appropriate surrogates to study disease pathogenesis or patient-specific therapeutics.

Miniaturized ascorbic acid assay platform based on point discharge atomic emission spectrometry coupling with gold filament enrichment.

BACKGROUND: Miniaturized microplasma-based atomic emission spectrometry (AES) has been extensively used for element analysis in recent years due to the advantages of low power consumption, low gas consumption, relatively low manufacturing and running cost, and the potential for real-time and field analysis. However, few applications in bioassay detection have been reported based on microplasma AES systems because of their relatively low sensitivity and the absence of indirect analytical strategies. It is still a challenge to develop a simple, sensitive, and portable microplasma-based AES bioassay approach. RESULTS: In this work, a portable analytical system was designed based on point discharge chemical vapor generation atomic emission spectrometry (PD-CVG-AES) coupling with gold filament enrichment. The detection of ascorbic acid (AA) was realized indirectly by means of the highly sensitive analysis of Hg2+. The measurement was based on Ag + can decrease the concentration of Hg2+ by forming Ag-Hg amalgam in the presence of the reductant SnCl2, while AA can pre-reduce Ag + to Ag0, leading to the generation of silver nanoparticles (Ag NPs). The pre-reduce procedure can decrease the generation of Ag-Hg amalgam, resulting in the recovery of Hg2+ signal. The dissociative Hg2+ was further detected by PD-CVG-AES combination of gold filament enrichment, which significantly improved the detection sensitivity for both Hg2+ and AA. Under optimal conditions, the limit of detection (LOD) of AA is as low as 19 nM with a relative standard deviation (RSD, n = 5) of 0.7 %. SIGNIFICANCE: The developed novel analytical strategy obviously broadens the application of microplasma-based AES, and it is well demonstrated by the determination of AA in several traditional Chinese medicines (TCMs), offering a higher level of sensitivity compared to current AA detection techniques. It has potential for future application in point-of-care testing (POCT) assays.

Bioactive tanshinone I inhibits the growth of lung cancer in part via downregulation of Aurora A function.

Lung cancer is the leading cause of cancer death in the world, and the searching for novel efficacious and safe agents for lung cancer prevention remains the top priority of lung cancer research. In the present study, we evaluated the effect of bioactive tanshinones from a Chinese herb Salvia miltiorrhiza, cryptotanshinone (CT), tanshinone I (T1) and tanshinone IIA (T2A), on the proliferation inhibition of lung cancer cell lines. Tanshinones inhibited the lung cancer cell proliferation in vitro, with T1 the most potent, via cell cycle arrest and apoptosis induction. Gene function assay showed that Aurora A knockdown by siRNA dramatically eliminated the T1 activity in vitro, suggesting that Aurora A is an important functional target for T1. We further evaluated the effectiveness of T1 on the growth of H1299 nonsmall lung cancer cell in a mouse model. Tanshinone I inhibited the growth of H1299 lung tumor in a dose-dependent manner. Tanshinone I at 200 mg/kg body weight significantly reduced final tumor weight by 34% (P < 0.05) associated with inhibiting proliferation and inducing apoptosis of lung cancer cells by 54% (P < 0.001) and 193% (P < 0.001), respectively, inhibiting lung tumor angiogenesis by 72% (P < 0.001), and reducing Aurora A expression by 67% (P < 0.001). On the other hand, T1 did not significantly alter food intake or body weight. Our results provided experimental evidence to suggest that T1 may be an efficacious and safe agent for the prevention of lung cancer progression and Aurora A may be an important molecular target for T1 action against lung cancer.

Underlying Mechanisms of Brain Aging and Neurodegenerative Diseases as Potential Targets for Preventive or Therapeutic Strategies Using Phytochemicals.

During aging, several tissues and biological systems undergo a progressive decline in function, leading to age-associated diseases such as neurodegenerative, inflammatory, metabolic, and cardiovascular diseases and cancer. In this review, we focus on the molecular underpinning of senescence and neurodegeneration related to age-associated brain diseases, in particular, Alzheimer's and Parkinson's diseases, along with introducing nutrients or phytochemicals that modulate age-associated molecular dysfunctions, potentially offering preventive or therapeutic benefits. Based on current knowledge, the dysregulation of microglia genes and neuroinflammation, telomere attrition, neuronal stem cell degradation, vascular system dysfunction, reactive oxygen species, loss of chromosome X inactivation in females, and gut microbiome dysbiosis have been seen to play pivotal roles in neurodegeneration in an interactive manner. There are several phytochemicals (e.g., curcumin, EGCG, fucoidan, galangin, astin C, apigenin, resveratrol, phytic acid, acacetin, daucosterol, silibinin, sulforaphane, withaferin A, and betulinic acid) that modulate the dysfunction of one or several key genes (e.g., TREM2, C3, C3aR1, TNFA, NF-kb, TGFB1&2, SIRT1&6, HMGB1, and STING) affected in the aged brain. Although phytochemicals have shown promise in slowing down the progression of age-related brain diseases, more studies to identify their efficacy, alone or in combinations, in preclinical systems can help to design novel nutritional strategies for the management of neurodegenerative diseases in humans.

Bioactive nutraceuticals oligo-lactic acid and fermented soy extract alleviate cognitive decline in mice in part via anti-neuroinflammation and modulation of gut microbiota.

Introduction: Cognition decline is associated with aging and certain diseases, such as neurodegenerative or neuropsychiatric disorders, diabetes and chronic kidney disease. Inflammation/neuroinflammation is considered an important causal factor, and experimental evidence suggests that anti-inflammatory natural compounds may effectively prevent cognitive decline. The goal of this study was to evaluate the effects of two natural bioactive agents, oligo-lactic acid (LAP) and fermented soy extract (ImmunBalance, IMB), on cognition in an adenine-induced cognitive impairment mouse model and to investigate the modulation of related biomarkers. Methods: Male C57 black mice were randomly assigned into the following experimental groups and received the corresponding treatments for 2 weeks before the use of adenine for model development: (1) negative control; (2) model control: injection of adenine at 50 mg/kg daily for 4 weeks; (3, 4) IMB groups: adenine injection and IMB oral gavage at 250 and 1,000 mg/kg BW, respectively; and (5) LAP group: adenine injection and LAP oral gavage at 1,000 mg/kg BW. One week after the model was developed, mice were evaluated for cognitive performances by using Y maze test, novel object recognition test, open field test, and Barnes maze tests. At the end of the experiment, brain tissues and cecum fecal samples were collected for analysis of gene expression and gut microbiota. Results: Mice treated with LAP or IMB had significantly improved spatial working memory, spatial recognition memory (LAP only), novel object recognition, and spatial learning and memory, compared with those in the model group. Gene expression analysis showed that, among a panel of cognition related genes, six of them (ELOVL2, GLUT4, Nestein, SNCA, TGFB1, and TGFB2) were significantly altered in the model group. LAP treatment significantly reversed expression levels of inflammatory/neuroinflammatory genes (SNCA, TGFB1), and IMB significantly reversed expression levels of genes related to inflammation/neuroinflammation, neurogenesis, and energy metabolism (ELOVL2, GLUT4, Nestin, TGFB1, and TGFB2). The altered microbiome was attenuated only by IMB. Discussion: In conclusion, our data showed that LAP improved cognition associated with regulating biomarkers related to neuroinflammation and energy metabolism, whereas IMB improved cognition associated with regulating biomarkers related to neuroinflammation, energy metabolism, and neurogenesis, and modulating gut microbiota. Our results suggest that LAP and IMB may improve cognitive performance in mice via distinct mechanisms of action.

Epigenetic Alterations of Brain Non-Neuronal Cells in Major Mental Diseases.

The tissue-specific expression and epigenetic dysregulation of many genes in cells derived from the postmortem brains of patients have been reported to provide a fundamental biological framework for major mental diseases such as autism, schizophrenia, bipolar disorder, and major depression. However, until recently, the impact of non-neuronal brain cells, which arises due to cell-type-specific alterations, has not been adequately scrutinized; this is because of the absence of techniques that directly evaluate their functionality. With the emergence of single-cell technologies, such as RNA sequencing (RNA-seq) and other novel techniques, various studies have now started to uncover the cell-type-specific expression and DNA methylation regulation of many genes (e.g., TREM2, MECP2, SLC1A2, TGFB2, NTRK2, S100B, KCNJ10, and HMGB1, and several complement genes such as C1q, C3, C3R, and C4) in the non-neuronal brain cells involved in the pathogenesis of mental diseases. Additionally, several lines of experimental evidence indicate that inflammation and inflammation-induced oxidative stress, as well as many insidious/latent infectious elements including the gut microbiome, alter the expression status and the epigenetic landscapes of brain non-neuronal cells. Here, we present supporting evidence highlighting the importance of the contribution of the brain's non-neuronal cells (in particular, microglia and different types of astrocytes) in the pathogenesis of mental diseases. Furthermore, we also address the potential impacts of the gut microbiome in the dysfunction of enteric and brain glia, as well as astrocytes, which, in turn, may affect neuronal functions in mental disorders. Finally, we present evidence that supports that microbiota transplantations from the affected individuals or mice provoke the corresponding disease-like behavior in the recipient mice, while specific bacterial species may have beneficial effects.

Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies.

Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes, drugs, and diet, are involved in the pathogenesis of depressive disorders. However, the underlying mechanisms of depression are complex and include the interaction of genetics with epigenetics and the host immune system. Modifications of the gut microbiome and its metabolites influence stress-related responses and social behavior in patients with depressive disorders by modulating the maturation of immune cells and neurogenesis in the brain mediated by epigenetic modifications. Here, we discuss the potential roles of a leaky gut in the development of depressive disorders via changes in gut microbiota-derived metabolites with epigenetic effects. Next, we will deliberate how altering the gut microbiome composition contributes to the development of depressive disorders via epigenetic alterations. In particular, we focus on how microbiota-derived metabolites such as butyrate as an epigenetic modifier, probiotics, maternal diet, polyphenols, drugs (e.g., antipsychotics, antidepressants, and antibiotics), and fecal microbiota transplantation could positively alleviate depressive-like behaviors by modulating the epigenetic landscape. Finally, we will discuss challenges associated with recent therapeutic approaches for depressive disorders via microbiome-related epigenetic shifts, as well as opportunities to tackle such problems.

Miniaturized point discharge optical emission spectrometry coupling with solid phase extraction: A robust approach for sensitive quantification of total mercury in mung bean sprout growth.

In this work, a portable chemical vapor generation point discharge optical emission spectrometry (CVG-PD-OES) system was designed for trace Hg2+ monitoring in mung bean sprout samples. The system incorporated selective solid phase extraction (SPE) to enhance the detection sensitivity. Gold nanoparticles (AuNPs) were prepared and utilized to extract trace amounts of Hg2+ by forming gold amalgam. Subsequently, the amalgam was desorbed using 5% HCl and introduced into a low-power PD-OES system analysis via CVG. A low limit of detection (LOD) of 0.16 ng mL-1 was obtained with a linear range of 0.5-6 ng mL-1. The well-designed system was successfully utilized for monitoring trace Hg2+ in the growth of mung beans. The results indicated that the Hg2+ in mung bean sprouts was continuously decreased during growth based on the metabolism. Furthermore, the risk assessment conducted implied a negligible hazard quotient, suggesting that the observed levels of exposure posed minimal risk.

Effects of a calcium/vitamin D/Zinc combination on anti-osteoporosis in ovariectomized rats.

BACKGROUND: Osteoporosis is a major health problem in postmenopausal women, and characterized by deteriorated bone mass and micro-architecture. There have been some clinical trials demonstrating the beneficial effects of vitamin-D and some trace elements on calcium absorption and attenuation of osteoporosis development. However, effects of the combination of vitamin-D and zinc on calcium absorption and osteoporosis have not been adequately investigated. METHODS: Network pharmacology was first performed to explore possible correlations between calcium/vitamin D/zinc and osteoporosis. Forty-nine female Sprague-Dawley rats (6 months old, 250 ± 20 g) were randomized into 7 experimental groups with 7 animals per group for the in vivo study, including one sham surgery control group, one ovariectomizing (OVX) group, and 5 OVX plus treatment groups. At the end of animal experiment, animal tibia and femur leg bones and blood were collected for H&E staining, bone microstructure analysis by a micro-CT, measurement of bone and serum Ca, P and Zn concentrations, and immunohistochemical detection of macrophage-colony stimulating factor receptor (M-CSFR) and receptor activator of nuclear factor-kappa B ligand (RANKL). RESULTS: The network pharmacology analysis identified 57 candidate targets that were related to the osteoporosis-Ca/VitD/Zn interconnections. Further pathway analysis suggested that the combined treatment of Ca, VitD and Zn attenuated osteoporosis via modulation of metabolic pathways. We found that a therapy with Ca/VitD-M/Zn-M (73 mg/kg/day Ca, 0.6 g/kg/day VitD3 and 0.6 mg/kg/day zinc citrate) could significantly suppress the progression of osteoporosis in rats. After the Ca/VitD-M/Zn-M treatment, the ratio of bone volume/tissue volume, trabecular number and the trabecular thickness were all significantly elevated while the extent of trabecular separation was significantly reduced. Additionally, both serum calcium and bone calcium levels were significantly upregulated by the Ca/VitD/Zn treatment in a dose-dependent manner. The combination of Ca/VitD-M/Zn-M was superiou to either Ca/VitD-L/Zn-L or Ca/VitD-H/Zn-H treatment for such an effect. Moreover, the osteoporosis-associated M-CSFR and RANKL factors were both significantly downregulated by the Ca/VitD-M/Zn-M treatment in bone tissues of OVX rats. CONCLUSIONS: The combined supplement of VitD and Zn facilitates the Ca(2 +) absorption and attenuates the development of osteoporosis via down-regulation of osteoporosis-associated factors M-CSFR and RANKL, thus potentially constitutes an alternative therapy for the postmenopausal osteoporosis.