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1.
Phys Chem Chem Phys ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35043815

RESUMO

Surface-enhanced Raman spectroscopy (SERS) finds wide applications in the field of organic molecule detection. However, reliable SERS detection of organic molecules and in situ monitoring of organic reactions under natural conditions by metal colloids are still challenging due to the formation of unstable nanoparticle clusters in solution and the low solubility of the organic molecules. Here, we approach the problems by introducing calcium ions to aggregate silver nanoparticles to form stable hot spots and acetone to promote uniform distribution of organic molecules on the nanoparticle surface. Significantly, our method exhibits stable SERS detection of up to 6 types of organic molecules in liquid. With acetone signals as an internal standard, we are able to determine molecule concentrations as well as monitor 3 kinds of organic reactions in situ. Our method shows potential for biomedical analysis, environmental analysis, and organic catalysis research.

2.
Gene ; 809: 146020, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34656743

RESUMO

Multi-lumbar vertebrae trait is a beneficial mutation that can significantly improve livestock meat production. However, the genetic basis of the multi-lumbar vertebrae in sheep is still unclear. Here, we analysed the number of lumbar vertebrae of Duolang sheep and found three different traits of lumbar vertebrae number. Compared with the normal sheep, the length and weight of animal carcass from the multi-lumbar vertebrae sheep increased by 2.21 cm and 0.78 kg, respectively. We performed high-throughput genome resequencing on multi-lumbar vertebrae (n = 18) and normal (n = 11) Duolang sheep and obtained a total of more than 528.87 GB data. We found that the most significantly selective region were located in the 49.68-49.74 MB of chromosome 4 by selective-sweep analysis. We annotated this region and found that it contains SFRP4 which is known to regulate bone development. We further used the PCR-SSCP technology to detect the single nucleotide polymorphism (SNP) of the putative candidate SFRP4 and found that the two SNPs (rs600370085:C > T and rs415133338: A > G) of this gene were significantly associated with the multi-lumbar vertebrae of Duolang sheep. Our study indicates that the SFRP4 may be a potential major gene that affects the number of lumbar vertebrae in Duolang sheep, and has the potential to be utilized for sheep breeding in the future.


Assuntos
Vértebras Lombares/fisiologia , Polimorfismo de Nucleotídeo Único , Carneiro Doméstico/genética , Animais , China , Estudo de Associação Genômica Ampla , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Proteínas Proto-Oncogênicas/genética
3.
Neural Regen Res ; 17(7): 1582-1587, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34916444

RESUMO

Subthreshold depression is a highly prevalent condition in adolescents who are at high risk for developing major depressive disorder. In preclinical models of neurological and psychiatric diseases, Lycium barbarum polysaccharide (LBP) extracted from Goji berries had anti-depressant effects including but not limited to anti-oxidative and anti-inflammatory properties. However, the effect of LBP on subthreshold depression is unclear. To investigate the clinical efficacy and safety of LBP for treating subthreshold depression in adolescents, we conducted a randomized, double-blind, placebo-controlled trial (RCT) with 29 adolescents with subthreshold depression recruited at The Fifth Affiliated Hospital of Guangzhou Medical University. The participants were randomly assigned to groups where they received either 300 mg LBP (LBP group, n = 15, 3 boys and 12 girls aged 15.13 ± 2.17 years) or a placebo (placebo group, n = 14, 2 boys and 12 girls aged 15 ± 1.71 years) for 6 successive weeks. Interim analyses revealed that the LBP group exhibited a greater change in Hamilton Depression Scale (HAMD-24) scores relative to the baseline and a higher remission rate (HAMD-24 total score ≤ 7) at 6 weeks compared with the placebo group. Scores on the Beck Depression Inventory-II (BDI-II), Pittsburgh Sleep Quality Index (PSQI), Kessler Psychological Distress Scale (Kessler), and Screen for Child Anxiety-Related Emotional Disorders (SCARED) were similar between the LBP and placebo groups. No side effects related to the intervention were reported in either group. These results indicate that LBP administration reduced depressive symptoms in adolescents with subthreshold depression. Furthermore, LBP was well tolerated with no treatment-limiting adverse events. Clinical trials involving a larger sample size are needed to further confirm the anti-depressive effects of LBP in adolescents with subthreshold depression. This study was approved by the Medical Ethics Committee of the Fifth Affiliated Hospital of Guangzhou Medical University (Guangzhou, China; approval No. L2019-08) on April 4, 2019 and was registered on ClinicalTrials.gov (identifier: NCT04032795) on July 25, 2019.

4.
Front Psychiatry ; 12: 774952, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880795

RESUMO

Objectives: The incidence of psychological and behavioral problems and depression among adolescents is increasing year by year, which has become an important public health problem. Alexithymia, as an important susceptible factor of adolescent depression, may continue to develop and strengthen under the stimulation of COVID-19-related stressors. However, no studies have focused on alexithymia in adolescent depression during the pandemic in China. This study aims to investigate the incidence and related factors of alexithymia in adolescent depression during the pandemic. Methods: Three hundred adolescent patients were enrolled from October 2020 to May 2021. The general demographic information of all participants was collected, and the clinical characteristics were assessed by the 20-item Toronto Alexithymia Scale (TAS-20), the Adolescent Self-Rating Life Events Check (ASLEC) List, the Childhood Trauma Questionnaire (CTQ), and the Positive and Negative Suicide Ideation (PANSI) Inventory. Results: The incidence of alexithymia was significantly higher among adolescents with depression (76.45%) during the pandemic. There were significant differences in school bullying, disease severity, ASLEC score, CTQ score and PANSI score between adolescents with and without alexithymia. In addition, learning stress, health and adaptation problems during the pandemic may be influential factors in alexithymia of adolescent depression (P < 0.05). Conclusions: According to the results, we found a high incidence of alexithymia in adolescent depression during the pandemic. More support and attention from families, schools and society is needed to develop preventive and targeted psychological interventions as early as possible.

5.
Beilstein J Org Chem ; 17: 2832-2839, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925622

RESUMO

The interaction between cucurbit[8]uril (Q[8]) and chloramphenicol (CPE) was investigated using single-crystal X-ray diffraction spectroscopy, isothermal titration calorimetry (ITC) and UV-vis, NMR and IR spectroscopy. The effects of Q[8] on the stability, in vitro release performance and antibacterial activity of CPE were also studied. The results showed that CPE and Q[8] formed a 1:1 inclusion complex (CPE@Q[8]) with an inclusion constant of 5.474 × 105 L/mol. The intervention of Q[8] did not affect the stability of CPE, but obviously reduced the release rate of CPE in artificial gastric and intestinal juice; Q[8] has a slow-release effect on CPE. The antibacterial results showed that the minimum inhibitory concentration (MIC) of CPE and CPE@Q[8] toward Escherichia coli (E. coli) was 1.5 × 10-3 and 1.0 × 10-3 mol/L, respectively, and toward Staphylococcus aureus (S. aureus), the MIC was 2.0 × 10-3 mol/L for both CPE and CPE@Q[8]. Therefore, Q[8] enhanced the inhibitory activity of CPE against E. coli.

6.
Int J Food Sci Nutr ; : 1-9, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34749580

RESUMO

The purpose of this cross-sectional study is to determine the association between yogurt consumption and lipid profiles in the general Chinese population. In this cross-sectional study, a total of 26,824 participants were included from Tianjin, China. Lipid profiles were determined by automated biochemical analyser. Yogurt consumption frequency was assessed by a validated food frequency questionnaire. Analysis of covariance was used to determine the association between daily yogurt consumption and lipid profiles. In the final multivariate model, daily yogurt consumption was negatively associated with triglyceride (TG) (p for trend <0.001) and positively associated with high density lipoprotein cholesterol (HDL-C) (p for trend = 0.02). There were no significant differences (p for trend >0.05) between daily yogurt consumption and total cholesterol (TC) or low density lipoprotein cholesterol (LDL-C). Results suggested that higher daily yogurt consumption was negatively correlated with TG and positively correlated with HDL-C in the general Chinese population.

7.
Front Psychiatry ; 12: 753909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733192

RESUMO

Objectives: Dementia of the Alzheimer's type (DAT) is the most common chronic neurodegenerative disease. At present, the pathogenesis of DAT is not completely clear, and there are no drugs that can cure the disease. Once an individual is diagnosed with DAT, the survival time is only 3 to 9 years. Therefore, there is an urgent need to determine the etiology of DAT and the associated influencing factors to find a breakthrough in the treatment of DAT. Methods: We studied the relationship between polymorphisms in several genes (including BIN1 and APOE) and DAT susceptibility and the effects of sex differences on DAT. Our study included 137 patients with DAT and 509 healthy controls (HCs). Results: The APOE rs429358 polymorphism CC and CT genotypes were associated with an increased risk of DAT in women. We found a significant association between APOE ε4 and DAT. The frequency of the ε4 allele in the DAT group (15.5%) was higher than that in the HC group (8.7%). The BIN1 rs7561528 polymorphism was associated with a decreased risk of DAT in men. Conclusions: APOE gene rs429358 and BIN1 gene 7561528 genes may affect the susceptibility to DAT in a Chinese Han population.

8.
BMC Dev Biol ; 21(1): 15, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715791

RESUMO

BACKGROUND: Tetraploid cotton plants serve as prime natural fiber source for the textile industry. Although various omics studies have revealed molecular basis for fiber development, a better understanding of transcriptional regulation mechanism regulating lint fiber initiation is necessary to meet global natural fiber demand. RESULTS: Here, we aimed to perform transcriptome sequencing to identify DEGs (differentially expressed genes) in ovules of the cotton variety Xu142 and its fibreless mutant Xu142fl during early lint fiber initiation period. Totally, 5516 DEGs including 1840 upregulated and 3676 downregulated were identified. GO enrichment analysis revealed that the downregulated DEGs were mainly associated with biological processes such as transcription related biosynthesis and metabolism, organic cyclic compound biosynthesis and metabolism, photosynthesis, and plant cell wall organization, with molecular functions involving transcription related binding, organic cyclic compound binding, and dioxygenase activity, while the upregulated DEGs were associated with DNA replication and phospholipid biosynthetic related processes. Among the 490 DEGs annotated as transcription factor genes, 86.5% were downregulated in the mutant including the Malvaceae-specific MMLs, expression patterns of which were confirmed during the central period of lint fiber initiation. Investigation of the 16 genes enriched in the cell wall organization revealed that 15 were EXPA coding genes. CONCLUSIONS: Overall, our data indicate that lint fiber initiation is a complicated process involving cooperation of multiple transcription factor families, which might ultimately lead to the reorganization of the cell wall and terminated cell division of the differentiating fiber initials.

9.
Front Psychiatry ; 12: 710498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566714

RESUMO

Objectives: Leptin is a crucial regulator of energy balance and is associated with obesity. In recent years, it has also been recognized as involved in the psychopathological mechanism. Our study aimed to elucidate the relationships between serum leptin levels, body mass index (BMI), and psychopathology symptoms in patients with schizophrenia. Methods: A cross-sectional assessment of 324 inpatients with schizophrenia was conducted. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS). Serum leptin levels were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA). Results: Significant differences in sex, BMI, and negative symptom subscale (PANSS-N) scores were found between the groups with high and low leptin levels in the study. Leptin levels were positively correlated with BMI (B = 2.322, t = 9.557, P < 0.001) and negatively correlated with PANSS-N scores (B = -0.303, t = -2.784, P = 0.006). Conclusions: Our results suggest that the increase in leptin levels is responsible for antipsychotic-induced weight gain and improved psychopathological symptoms.

11.
Sci Rep ; 11(1): 16338, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381161

RESUMO

Making low GI of the Chinese steamed bread (CSB) with acceptable eating quality is a challenge. A CSB prepared from wheat flour partially substituted by lotus root powder (LRP) showed good prospects. RVA profile and texture profile were determined to evaluate the texture, while animal test were used to confirm the bio-functional attributes. The addition of LRP effectively changed the RVA profile of lotus-wheat incorporated flour (LWIF). CSB prepared from 30% LWIF showed acceptable eating quality with higher springiness, cohesiveness, and recovery while lower hardness. After 12 weeks of 30% LWIF administrating, the fast blood glucose of diabetic rat decreased from 17.6 to 5.8 mmol/L together with the reduction of serum TC, TG and LDL-C. The hepatic histopathological examination and serum levels changes of SOD, CAT and FFA confirmed LWIF could effectively protect the liver of the diabetic rats from damage caused by oxidative stress.


Assuntos
Pão/análise , Farinha/análise , Lotus/química , Raízes de Plantas/química , Pós/química , Triticum/química , Animais , Glicemia/efeitos dos fármacos , China , Culinária/métodos , Diabetes Mellitus Experimental/tratamento farmacológico , Fermentação/fisiologia , Manipulação de Alimentos/métodos , Glutens/química , Dureza , Fígado/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Vapor
12.
Biochem Biophys Res Commun ; 570: 8-14, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34271438

RESUMO

Large conductance calcium-activated potassium channel (BK channel) is widely expressed in skeletal muscle, myocardium, smooth muscle and other muscle tissues. Mutation, abnormal expression and altered activity of BK channel are linked to muscle-related diseases such as dyskinesia, epilepsy and erectile dysfunction. In order to compare the effects of BK channel on different muscle tissues, we constructed BK channel gene knockout rats||||||| (BK-/- rats). HE staining, open field and grip strength tests, ultrasound, blood pressure measurement and vascular tension test were utilized to explore the effects of BK channel deletion on the structure and function changes in skeletal muscle, myocardium, and vascular smooth muscle (VSM). It was found that compared with wild-type rats, the BK-/- rats showed decreased skeletal muscle fiber area, grip, movement distance and speed at 2 and 12 months of ages. At heart, the muscle fiber area, cardiac systolic/diastolic function and heart rate decreased in BK-/- rats. The wall of the left ventricle became thin. However, the vascular wall of BK-/- rats thickened, the pulse wave velocity was increased, and the VSM contraction was enhanced. Unexpectedly, both systolic and diastolic blood pressure were reduced in BK-/- rats, while pulse pressure difference was increased. These results suggest that BK channel may have different effects on different types of muscle tissue, and it should be noted that different parts of muscle tissue may have different effects when BK channel-related drugs are used.


Assuntos
Deleção de Genes , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Músculo Liso/fisiologia , Miocárdio/metabolismo , Animais , Vasos Sanguíneos/fisiologia , Diástole/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Condicionamento Físico Animal , Ratos , Sístole/fisiologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-34254931

RESUMO

BACKGROUND: Circular RNAs (circRNAs) play an essential role in developing tumors, but their role in non-small cell lung cancer (NSCLC) is unclear. Thus, the present study explored the possible molecular mechanism of circRNAs in NSCLC. METHODS: Three circular RNA (circRNA) microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differential expressions of circRNAs (DECs) were identified in NSCLC tissue and compared to adjacent healthy tissue. The online cancer-specific circRNA database (CSCD) was used for the analysis of the DECs function. Protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Cytoscape, and UALCAN were used to predict the critical nodes and perform patient survival analysis, respectively. The interaction between the DECs, the predicted miRNAs, and hub genes was also determined. Finally, the circRNA-miRNA-mRNA network was established. RESULTS: The expression of hsa_circ_0049271, hsa_circ_0026337, hsa_circ_0043256, and hsa_circ_0008234 was decreased in NSCLC tissues. The Encyclopedia of RNA Interactomes (ENCORI) and CSCD database results showed that hsa_circ_0026337 was found to sponge with miR-1193, miR-197-3p, miR-3605-5p, miR-433-3p, and miR-652-3p, and hsa_circ_0043256 to sponge with miR-1252-5p, miR-494-3p, and miR-558, respectively. Subsequently, 100 mRNAs were predicted to bind with these seven miRNA response elements (MREs). The GO analysis and KEGG pathway revealed that these 100 MREs might be involved in "histone deacetylase binding" and "cellular senescence". PPI network and Cytoscape identified the top ten hub genes. Survival analysis data showed that the low expression of hsa_circ_0026337 was significantly associated with shortened survival time in NSCLC (P=0.037), which increased the expression level of hsa-miR-197-3p, thereby inhibiting the translation of specific proteins. CONCLUSION: This study examined the circRNA-miRNA-mRNA regulatory network associated with NSCLC and explored the potential functions of DECs in the network to elucidate the mechanisms underlying disease progression in NSCLC.

14.
Front Vet Sci ; 8: 603919, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34179152

RESUMO

Bovine Viral Diarrhea Virus (BVDV) is the main pathogen of bovine viral diarrhea disease (BVD), which leads to enormous economic losses in the cattle industry. A sensitive and specific detection for BVDV is advantageous to the control of BVDV. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have been used for detecting virus RNA. In this study, the expression and purification of LwCas13a protein was optimized and the RNase activity of LwCas13a in vitro was verified. CRISPR-LwCas13a system could detect BVDV virus and BVDV RNA with high specificity and simplicity. The detection limit of the LwCas13a system was 103 pM, and there were no cross-reactions with HEK293T and MDBK. In summary, a sensitive, specific, and simple nucleic acid detection method based on CRISPR-Cas13a was developed for BVDV. This method provides a new detection strategy for early diagnosis of BVDV.

15.
Environ Sci Pollut Res Int ; 28(32): 43287-43314, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34185270

RESUMO

Knowledge of the behavior of highly compacted expansive clays, as an engineered barrier, in disposal of high-level nuclear waste (HLW) systems to prevent the pollution due to migration of radionuclide is extremely essential. The prominent properties of globally and widely used bentonites have been extensively studied during past two decades. In China, GaoMiaoZi (GMZ) bentonite is the first choice as a buffer or backfill material for deep geological repositories. This review article presents the recent progresses of knowledge on water retention properties, hydromechanical behavior, and fractal characteristics of GMZ bentonite-based materials, by reviewing 217 internationally published research articles. Firstly, the current literature regarding hydrogeochemical and mechanical characteristics of GMZ bentonite influenced by various saline solutions are critically summarized and reviewed. Then, the role of osmotic suction π alongside the application of surface fractal dimension Ds is presented from the standpoint of fractal theory. Finally, the strength characteristics of GMZ bentonites using fractal approach have been discussed. Furthermore, this study sheds light on gaps, opportunities, and further research for understanding and analyzing the long-term hydromechanical characteristics of the designed backfill material, from the standpoint of surface fractality of bentonites, and implications of sustainable buffer materials in the field of geoenvironmental engineering.


Assuntos
Resíduos Radioativos , Eliminação de Resíduos , Bentonita , Argila , Fractais , Resíduos Radioativos/análise
16.
Adv Mater ; 33(30): e2006004, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34145654

RESUMO

Surfaces and heterojunction interfaces, where defects and energy levels dictate charge-carrier dynamics in optoelectronic devices, are critical for unlocking the full potential of perovskite semiconductors. In this progress report, chemical structures of perovskite surfaces are discussed and basic physical rules for the band alignment are summarized at various perovskite interfaces. Common perovskite surfaces are typically decorated by various compositional and structural defects such as residual surface reactants, discrete nanoclusters, reactions by products, vacancies, interstitials, antisites, etc. Some of these surface species induce deep-level defect states in the forbidden band forming very harmful charge-carrier traps and affect negatively the interface band alignments for achieving optimal device performance. Herein, an overview of research progresses on surface and interface engineering is provided to minimize deep-level defect states. The reviewed subjects include selection of interface and substrate buffer layers for growing better crystals, materials and processing methods for surface passivation, the surface catalyst for microstructure transformations, organic semiconductors for charge extraction or injection, heterojunctions with wide bandgap perovskites or nanocrystals for mitigating defects, and electrode interlayer for preventing interdiffusion and reactions. These surface and interface engineering strategies are shown to be critical in boosting device performance for both solar cells and light-emitting diodes.

17.
Chem Commun (Camb) ; 57(41): 5082-5085, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33890586

RESUMO

Two polymorphs of Cu[(3,4-bis(diphenylphosphino)thiophene)(bis(pyrazol-1-yl)borohydrate)] (1) were isolated. The blue luminescent crystals have evident mechanochromic luminescent (MCL) properties. Based on photophysical and structural analysis, the pore structure in the blue crystals is considered to be the main reason for the MCL properties.

18.
BMC Chem ; 15(1): 14, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648574

RESUMO

The polyphenol distribution in fresh waxy corns of different color varieties and their functional activities, which may be useful for treating various chronic diseases, were investigated. The in vitro antioxidant activity, and hypoglycemic and hypocholesterolemic effects of the free and bound corn phenolics were determined to evaluate the edible value of fresh waxy corn. The colored varieties contained more phenols than the common varieties (white and/or yellow). The total free phenolic acid content of the six varieties was 6637.73 µg/g DW (dry weight), which was slightly higher (P > 0.05) than that of the total bound form (6276.65 µg/g DW). The total free flavonoid content was 5850.09 µg/g DW, which was higher (P < 0.05) than that of the total bound form (4874.51µg/g DW). No bound anthocyanin was detected in the methanol extracts of the tested varieties. For all the varieties, free polyphenols contributed 86-100 % and 70-78 % of the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging abilities, respectively, and 100 % of the ferric reducing capacity. The free phenolics in fresh waxy corn showed better (P < 0.05) hypoglycemic effect than the bound form in terms of inhibition of α-amylase activity, whereas the bound phenolics of most varieties showed higher α-glucosidase inhibitory activity than the free forms. The free phenolics showed better (P < 0.05) glycocholesterol binding than the bound form for all varieties. The bound polyphenols showed better sodium cholate and taurocholate binding than the free form for most varieties. In conclusion, the difference between free and bound polyphenol content and functional activities indicates that fresh waxy corn can be potentially used for the development of functional food.

19.
Front Pharmacol ; 12: 619288, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746756

RESUMO

Depressive disorder is a common mental disorder characterized by depressed mood and loss of interest or pleasure. As the Herbal medicines are mainly used as complementary and alternative therapy for depression. This study aimed at exploring antidepressant activity of Huang-lian Jie-du Decoction (HLJDD), and evaluating active components and potential depression-associated targets. HLJDD was administered on chronic unpredictable mild stress-induced (CUMS) depressive mice. Behavior evaluation was performed through force swimming test (FST), novelty-suppressed feeding test (NSF), and open field test (OFT). Active components of HLJDD, potential targets, and metabolic pathways involved in depression were explored through systemic biology-based network pharmacology assay, molecular docking and metabonomics. FST assay showed that CUMS mice administered with HLJDD had significantly shorter immobility time compared with control mice. Further, HLJDD alleviated feeding latency of CUMS mice in NSFand increased moving distance and duration in OFT. In the following network pharmacology assay, thirty-eight active compounds in HLJDD were identified based on drug-like characteristics, and pharmacokinetics and pharmacodynamics profiles. Moreover, forty-eight molecular targets and ten biochemical pathways were uncovered through molecular docking and metabonomics. GRIN2B, DRD, PRKCA, HTR, MAOA, SLC6A4, GRIN2A, and CACNA1A are implicated in inhibition of depressive symptoms through modulating tryptophan metabolism, serotonergic and dopaminergic synaptic activities, cAMP signaling pathway, and calcium signaling pathway. Further network pharmacology-based analysis showed a correlation between HLJDD and tryptophan metabolism. A total of thirty-seven active compounds, seventy-six targets, and sixteen biochemical pathways were involved in tryptophan metabolism. These findings show that HLJDD acts on potential targets such as SLC6A4, HTR, INS, MAO, CAT, and FoxO, PI3K/Akt, calcium, HIF-1, and mTOR signaling pathways, and modulates serotoninergic and dopaminergic synaptic functions. In addition, metabonomics showed that tryptophan metabolism is the primary target for HLJDD in CUMS mice. The findings of the study show that HLJDD exhibited antidepressant effects. SLC6A4 and MAOA in tryptophan metabolism were modulated by berberine, baicalein, tetrahydroberberine, candicine and may be the main antidepressant targets for HLJDD.

20.
Psychopharmacology (Berl) ; 238(7): 1979-1990, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33774704

RESUMO

RATIONALE AND OBJECTIVE: Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. METHODS: We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. RESULTS: Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-ß levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients' BMI, blood glucose, and proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1ß and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. CONCLUSION: Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.


Assuntos
Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Citocinas/sangue , Mediadores da Inflamação/sangue , Doenças Metabólicas/sangue , Doenças Metabólicas/induzido quimicamente , Adulto , Animais , Antipsicóticos/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Clozapina/uso terapêutico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue
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