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1.
Mol Ther ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34998953

RESUMO

Prime Editor (PE) has tremendous promise for gene therapy. However, it remains a challenge to deliver PE (>6.3 kb) in vivo. Although PE can be split into two fragments and delivered using dual adeno-associated viruses (AAVs), choice of split sites within Cas9 - which affects editing efficiency - is limited due to the large size of PE. Furthermore, overexpressing reverse transcriptase in mammalian cells might disrupt translation termination via its RNase H domain. Here, we developed a compact PE without the RNase H domain that showed comparable editing to full-length PE. With compact PE, we used a Cas9 split site (Glu 573) that supported robust editing in cells (up to 93% of full-length PE) and in mouse liver. We then demonstrated that split-cPE573 delivered by dual-AAV8 efficiently mediated a 3-bp TGA insertion in the Pcsk9 gene in mouse liver. Compact PE without the RNase H domain abolished its binding to eukaryotic translation termination factor 1 (eRF1) and mitigated the stop codon readthrough effect observed with full-length PE. This study identifies a compact PE with a flexible split design to advance utility of prime editing in vivo.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35020417

RESUMO

Background: The bZIP gene family plays roles in biotic and abiotic stress, secondary metabolism, and other aspects in plants. They have been reported in Arabidopsis thaliana, Oryza sativa, Artemisia annua, and other plants, but their roles in Cannabis sativa have not been determined. Materials and Methods: In this study, we analyzed the genome-wide identification and expression profile of the bZIP gene family in C. sativa. Results: A total of 51 members of the bZIP gene family were identified based on the C. sativa genome and numbered in order from CsbZIP1 to CsbZIP51. Their phylogenetic relationships, cis-elements in promoter region, gene structures and motif compositions, physicochemical properties, chromosome locations, and expression profiles, were analyzed. The results showed that the 51 CsbZIPs were unevenly distributed on 10 chromosomes and could be clustered into 11 subfamilies. Furthermore, CsbZIPs located in the same subfamilies presented similar intron/exon organization and motif composition. The expression levels of CsbZIPs in various tissues (flowers, bracts, vegetative leaves, stems, and seeds) were determined using reverse transcription quantitative polymerase chain reaction. The expression levels of CsbZIPs were higher in flowers and bracts. The 51 CsbZIPs were explored, and their structure, evolution, and expression pattern in different tissues of C. sativa were characterized synthetically. The findings indicated that CsbZIPs are essential for the growth and development of C. sativa. Conclusions: These results provide a theoretical basis for subsequent research on hemp bZIP transcription factors and the cultivation of high-cannabidiol and low-tetrahydrocannabinol high-quality cannabis varieties.

3.
J Sci Food Agric ; 102(2): 617-627, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34148237

RESUMO

BACKGROUND: Cooked meat is a good source of high-quality protein. However, during long-term cooking of meat, radical-induced lipid and protein oxidation may lead to the formation of poisonous compounds, such as heterocyclic amines (HAs). This work investigated a testing method for HAs and it describes that cooking temperature, cooking time and repeated cooking times have influences on the overall quality of braised sauce beef and the effect of HAs formation. RESULTS: The improved method has a good separation effect on nine kinds of HAs. The average recovery of HAs at two spiked levels is between 51.70% and 88.25% (n = 6). The detection limit is 0.025-0.060 ng g-1 , and the limit of quantitation is 0.070-0.160 ng g-1 . Only harman and norharman were detected in samples. Cooking time and cooking temperature will affect the quality and HA content of samples. When the braised sauce beef soup was cooked 20 times, the HA content was the highest - as high as 21.43 ng g-1 . The more times the beef was cooked repeatedly, the higher was the HA content. Under different cooking conditions, glucose has a significant effect on the formation of ß-carboline. CONCLUSION: We have established a detection method for HAs with good repeatability and accuracy. HAs were more easily formed in braised sauce beef by high temperature, long heating and repeated brine cooking. © 2021 Society of Chemical Industry.


Assuntos
Aminas/química , Culinária/métodos , Compostos Heterocíclicos/química , Carne/análise , Animais , Bovinos , Temperatura Alta , Fatores de Tempo
4.
Neural Regen Res ; 17(3): 682-689, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34380910

RESUMO

SNCA, GBA, and VPS35 are three common genes associated with Parkinson's disease. Previous studies have shown that these three genes may be associated with Alzheimer's disease (AD). However, it is unclear whether these genes increase the risk of AD in Chinese populations. In this study, we used a targeted gene sequencing panel to screen all the exon regions and the nearby sequences of GBA, SNCA, and VPS35 in a cohort including 721 AD patients and 365 healthy controls from China. The results revealed that neither common variants nor rare variants of these three genes were associated with AD in a Chinese population. These findings suggest that the mutations in GBA, SNCA, and VPS35 are not likely to play an important role in the genetic susceptibility to AD in Chinese populations. The study was approved by the Ethics Committee of Xiangya Hospital, Central South University, China on March 9, 2016 (approval No. 201603198).

5.
Leuk Lymphoma ; : 1-9, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34877904

RESUMO

All-trans retinoic acid-based differentiation therapies have succeeded in the treatment of acute promyelocytic leukemia, which is a rare subtype of acute myeloid leukemia (AML). Their clinical efficacy is negligible, however, for other subtypes of AML. Here, we showed that strobilurin derivatives, a well-established class of inhibitors of mitochondrial electron transport chain (ETC) complex III, possessed differentiation-inducing activity in AML cells. Impairment of mitochondrial ETC activity was involved in the differentiation effects of strobilurin derivatives, where reactive oxygen species generation appeared unnecessary. Conversely, strobilurin derivative-mediated differentiation was triggered by pyrimidine deficiency, which resulted from the inhibition of the mitochondrial-coupled dihydroorotate dehydrogenase enzyme. Moreover, strobilurin derivative-mediated pyrimidine depletion led to the activation of the Akt/mTOR cascade, which was required for the differentiation. Our study provided evidence that strobilurin derivatives may represent a novel class of differentiation-inducing agents for the treatment of AML.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34851094

RESUMO

Heterostructures of quantum dots (QDs) and two-dimensional (2D) materials show promising potential for photodetection applications owing to their combination of high optical absorption and good in-plane carrier mobility. In this work, the performance of QD-2D photodetectors is tuned by band engineering. Devices are fabricated by coating MoS2 nanosheets with InP QDs, type-I core-shell InP/ZnS QDs, and type-II core-shell InP/CdS QDs. Comparative spectroscopic and photoelectric studies of different hybrids show that the energy band alignment and shell thickness can influence the efficiency of charge transfer (CT), energy transfer (ET), and defect-related processes between QDs and MoS2. Benefiting from efficient CT between the QDs and MoS2, a significant enhancement of responsivity and detectivity is observed in thick-shell InP/CdS QD-MoS2 devices. Our results demonstrate the feasibility of using core-shell QDs for regulating the ET and CT efficiency in heterostructures and highlight the importance of interface band design in QD-2D and other low-dimensional photodetectors.

7.
Front Public Health ; 9: 739828, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869153

RESUMO

Background: International travel during the Coronavirus disease 2019 (COVID-19) pandemic carries a certain magnitude of infection risk both to travelers and their destination, which may be difficult to assess in the early stage. The characteristics of common infectious diseases of tourists may provide some clues to identify the high-risk travelers and protect susceptible population. Methods: From among 48,444 travelers screened at Shanghai Port, we analyzed 577 travelers with 590 infectious diseases for age, sex, disease type, and World Health Organization (WHO) regions. We used the Joinpoint Regression Program to identify the average percent changes (APC) in the various trends among these individuals. Results: Hepatitis B, syphilis, and HIV were the most common infectious diseases in travelers entering China, and Hepatitis B, pulmonary tuberculosis, and syphilis in Chinese nationals traveling abroad (overall detection rates, 1.43 and 0.74%, respectively; P < 0.05). Africa (2.96%), the Americas (1.68%), and the Western Pacific (1.62%) exhibited the highest detection rates. This trend did not decrease since the COVID-19 pandemic (P > 0.05) and rather showed an upward trend with increasing age [APC 95% CI = 5.46 (3.41,7.56)%, P < 0.05]. However, there were no evident trends in monthly infection rates of travelers exiting and entering China from different WHO regions (all P > 0.05). Conclusion: Travelers always carry a transmission risk of common infectious diseases. It may be reasonable to adjust strategies for airport screening and quarantine according to the age and departure area of travelers to prevent and control new infectious diseases.

8.
Mikrochim Acta ; 189(1): 14, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34870771

RESUMO

In the ongoing COVID-19 pandemic, simple, rapid, point-of-care tests not requiring trained personnel for primary care testing are essential. Saliva-based antigen rapid tests (ARTs) can fulfil this need, but these tests require overnight-fasted samples; without which independent studies have demonstrated sensitivities of only 11.7 to 23.1%. Herein, we report an Amplified Parallel ART (AP-ART) with sensitivity above 90%, even with non-fasted samples. The virus was captured multimodally, using both anti-spike protein antibodies and Angiotensin Converting Enzyme 2 (ACE2) protein. It also featured two parallel flow channels. The first contained spike protein binding gold nanoparticles which produced a visible red line upon encountering the virus. The second contained signal amplifying nanoparticles that complex with the former and amplify the signal without any linker. Compared to existing dual gold amplification techniques, a limit of detection of one order of magnitude lower was achieved (0.0064 ng·mL-1). AP-ART performance in detecting SARS-CoV-2 in saliva of COVID-19 patients was investigated using a case-control study (139 participants enrolled and 162 saliva samples tested). Unlike commercially available ARTs, the sensitivity of AP-ART was maintained even when non-fasting saliva was used. Compared to the gold standard reverse transcription-polymerase chain reaction testing on nasopharyngeal samples, non-fasting saliva tested on AP-ART showed a sensitivity of 97.0% (95% CI: 84.7-99.8); without amplification, the sensitivity was 72.7% (95% CI: 83.7-94.8). Thus, AP-ART has the potential to be developed for point-of-care testing, which may be particularly important in resource-limited settings, and for early diagnosis to initiate newly approved therapies to reduce COVID-19 severity.

9.
Chem Commun (Camb) ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34889324

RESUMO

A proton-transporting pathway is crucial to the conduction mechanism in fuel cells and biological systems. Here, we report a novel 5-fold interpenetrated three-dimensional (3D) hydrogen-bonded quadruplex framework, which exhibits an ultrahigh single-crystal proton conductivity of 1.2(1) × 10-2 S cm-1 at 95 °C and 98% relative humidity, benefitting from the spiral H3O+/H2O chains in 1D pore channels studded with COOH/COO- groups.

10.
J Alzheimers Dis ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34864672

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a chronic and fatal neurodegenerative disease; accumulating evidence suggests that vitamin deficiency is associated with the risk of AD. However, studies attempting to elucidate the relationship between vitamins and AD varied widely. OBJECTIVE: This study aimed to investigate the relationship between serum vitamin levels and AD in a cohort of the Chinese population. METHODS: A total of 368 AD patients and 574 healthy controls were recruited in this study; serum vitamin A, B1, B6, B9, B12, C, D, and E were measured in all participants. RESULTS: Compared with the controls, vitamin B2, B9, B12, D, and E were significantly reduced in AD patients. Lower levels of vitamin B2, B9, B12, D, and E were associated with the risk of AD. After adjusting for age and gender, low levels of vitamin B2, B9, and B12 were still related to the risk of AD. In addition, a negative correlation was determined between vitamin E concentration and Activity of Daily Living Scale score while no significant association was found between serum vitamins and age at onset, disease duration, Mini-Mental State Examination, and Neuropsychiatric Inventory Questionnaire score. CONCLUSION: We conclude that lower vitamin B2, B9, B12, D, and E might be associated with the risk of AD, especially vitamin B2, B9, and B12. And lower vitamin E might be related to severe ability impairment of daily activities.

11.
Front Neurosci ; 15: 738167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34924927

RESUMO

Inspired by the neuroscience research results that the human brain can produce dynamic responses to different emotions, a new electroencephalogram (EEG)-based human emotion classification model was proposed, named R2G-ST-BiLSTM, which uses a hierarchical neural network model to learn more discriminative spatiotemporal EEG features from local to global brain regions. First, the bidirectional long- and short-term memory (BiLSTM) network is used to obtain the internal spatial relationship of EEG signals on different channels within and between regions of the brain. Considering the different effects of various cerebral regions on emotions, the regional attention mechanism is introduced in the R2G-ST-BiLSTM model to determine the weight of different brain regions, which could enhance or weaken the contribution of each brain area to emotion recognition. Then a hierarchical BiLSTM network is again used to learn the spatiotemporal EEG features from regional to global brain areas, which are then input into an emotion classifier. Especially, we introduce a domain discriminator to work together with the classifier to reduce the domain offset between the training and testing data. Finally, we make experiments on the EEG data of the DEAP and SEED datasets to test and compare the performance of the models. It is proven that our method achieves higher accuracy than those of the state-of-the-art methods. Our method provides a good way to develop affective brain-computer interface applications.

12.
Bioorg Chem ; 119: 105469, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34915285

RESUMO

Targeting EGFR and HER-2 is an essential direction for cancer treatment. Here, a series of N-(1,3,4-thiadiazol-2-yl)benzamide derivatives containing a 6,7-methoxyquinoline structure was designed and synthesized to serve as EGFR/HER-2 dual-target inhibitors. The kinase assays verified that target compounds could inhibit the kinase activity of EGFR and HER-2 selectively. The results of CCK-8 and 3D cell viability assays confirmed that target compounds had excellent anti-proliferation ability against breast cancer cells (MCF-7 and SK-BR-3) and lung cancer cells (A549 and H1975), particularly against SK-BR-3 cells, while the inhibitory effect on healthy breast cells (MCF-10A) and lung cells (Beas-2B) was weak. Among them, the hit compound YH-9 binded to EGFR and HER-2 stably in molecular dynamics studies. Further studies found thatYH-9could induce the release of cytochrome c and inhibit proliferation by promoting ROS expression in SK-BR-3 cells. Moreover,YH-9could diminish the secretion of VEGF and bFGF factors in SK-BR-3 cells, then inhibited tube formation and angiogenesis. Notably,YH-9could effectively inhibit breast cancer growth and angiogenesis with little toxicity in the SK-BR-3 cell xenograft model. Taken together,in vitroandin vivoresults revealed that YH-9 had high drug potential as a dual-target inhibitor of EGFR/HER-2 to inhibit breast cancer growth and angiogenesis.

13.
J Virol ; : JVI0169321, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34908446

RESUMO

Epstein-Barr virus (EBV) infection is associated with multiple malignancies, including pulmonary lymphoepithelioma-like carcinoma (pLELC), a particular subtype of primary lung cancer. However, the genomic characteristics of EBV related to pLELC remain unclear. Here, we obtained the whole-genome dataset of EBV isolated from 78 pLELC patients and 37 healthy controls using EBV-captured sequencing. Compared to the reference genome (NC_007605), a total of 3995 variations were detected across pLELC-derived EBV sequences, with the mutational hotspots located in latent genes. Combined with 180 published EBV sequences derived from healthy people in Southern China, we performed a genome-wide association study and identified 32 variations significantly related to pLELC (p < 2.56×10-05, Bonferroni correction), with the top signal of SNP coordinate T7327C (OR = 1.22, p = 2.39×10-15) locating in the origin of plasmid replication (OriP). The results of population structure analysis of EBV isolates in East Asian showed the EBV strains derived from pLELC were more similar to those from nasopharyngeal carcinoma (NPC) than other EBV-associated diseases. In addition, typical latency type-II infection were recognized for EBV of pLELC at both transcription and methylation levels. Taken together, we defined the global view of EBV genomic profiles in pLELC patients for the first time, providing new insights to deepening our understanding of this rare EBV-associated primary lung carcinoma. Importance Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rarely distinctive subtype of primary lung cancer closely associated with Epstein-Barr virus (EBV) infection. Here, we gave the first overview of pLELC-derived EBV at the level of genome, methylation and transcription. We obtained the EBV sequences dataset from 78 primary pLELC patients, and revealed the sequences diversity across EBV genome and detected variability in known immune epitopes. Genome-wide association analysis combining 217 healthy controls identifies significant variations related to the risk of pLELC. Meanwhile, we characterized the integration landscapes of EBV at the genome-wide level. These results provided new insight for understanding EBV's role in pLELC tumorigenesis.

14.
Pak J Med Sci ; 37(7): 1965-1971, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912427

RESUMO

Objective: To evaluate the effect and clinical significance of tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with Erectile dysfunction (ED). Methods: Eighty patients with hyperlipidemia complicated with ED who were treated at The Second Hospital of Hebei Medical University from January 2019 to June 2020 were selected. Using a completely randomized design experimental method, these 80 patients were randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. The control group was treated with a single drug, atorvastatin calcium, while the experimental group was given tadalafil orally on the basis of the control group for 3 months. Changes in the levels of inflammatory factors such as IL-6, TNF and CRP, adverse drug reactions, changes in hemodynamic indicators such as HSV, LSV, PSV, HCT and ESR before and after treatment, as well as changes in sexual function after treatment were compared and analyzed between the two groups. Results: TNF-a, CRP and IL-6 in the experimental group were significantly lower than those in the control group after treatment, with statistically significant differences (p<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (p=0.18). After treatment, hemodynamic indexes and sexual function indexes of the experimental group were significantly improved compared with those in the control group, with statistically significant differences (p<0.05). Conclusion: A significant improvement effect can be achieved by tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with ED. At the same time, the combination of the two has synergism on inflammatory factors and blood rheology, and the incidence of adverse reactions is not significantly increased.

15.
Biofabrication ; 14(1)2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-34905737

RESUMO

In the past decade, cartilage tissue engineering has arisen as a promising therapeutic option for degenerative joint diseases, such as osteoarthritis, in the hope of restoring the structure and physiological functions. Hydrogels are promising biomaterials for developing engineered scaffolds for cartilage regeneration. However, hydrogel-delivered mesenchymal stem cells or chondrocytes could be exposed to elevated levels of reactive oxygen species (ROS) in the inflammatory microenvironment after being implanted into injured joints, which may affect their phenotype and normal functions and thereby hinder the regeneration efficacy. To attenuate ROS induced side effects, a multifunctional hydrogel with an innate anti-oxidative ability was produced in this study. The hydrogel was rapidly formed through a dynamic covalent bond between phenylboronic acid grafted hyaluronic acid (HA-PBA) and poly(vinyl alcohol) and was further stabilized through a secondary crosslinking between the acrylate moiety on HA-PBA and the free thiol group from thiolated gelatin. The hydrogel is cyto-compatible and injectable and can be used as a bioink for 3D bioprinting. The viscoelastic properties of the hydrogels could be modulated through the hydrogel precursor concentration. The presence of dynamic covalent linkages contributed to its shear-thinning property and thus good printability of the hydrogel, resulting in the fabrication of a porous grid construct and a meniscus like scaffold at high structural fidelity. The bioprinted hydrogel promoted cell adhesion and chondrogenic differentiation of encapsulated rabbit adipose derived mesenchymal stem cells. Meanwhile, the hydrogel supported robust deposition of extracellular matrix components, including glycosaminoglycans and type II collagen, by embedded mouse chondrocytesin vitro. Most importantly, the hydrogel could protect encapsulated chondrocytes from ROS induced downregulation of cartilage-specific anabolic genes (ACAN and COL2) and upregulation of a catabolic gene (MMP13) after incubation with H2O2. Furthermore, intra-articular injection of the hydrogel in mice revealed adequate stability and good biocompatibilityin vivo. These results demonstrate that this hydrogel can be used as a novel bioink for the generation of 3D bioprinted constructs with anti-ROS ability to potentially enhance cartilage tissue regeneration in a chronic inflammatory and elevated ROS microenvironment.

16.
Am J Transl Res ; 13(11): 12549-12556, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956472

RESUMO

BACKGROUND: Increasing evidences have indicated the association of non-coding RNAs with the progression of lumbar disc degeneration (LDD), but the role of lncRNA ZFAS1 in LDD remains undefined. Therefore, this study was designed to determine the predictive value of lncRNA ZFAS1 in patients with LDD. METHODS: A total of 80 patients with LDD confirmed and treated in the Gansu Provincial Hospital from May 2018 to May 2020 were enrolled into the patient group, and 50 healthy controls who concurrently underwent physical examination in our hospital were enrolled into the control group. The expression and diagnostic value of serum lncRNA ZFAS1 in the two groups were determined. The expression of lncRNA ZFAS1 was compared between the two groups before and one month after therapy, and the associations of lncRNA ZFAS1 with inflammatory factors were analyzed. In addition, logistic regression was carried out to analyze risk factors for the prognosis of patients, and corresponding curves about prediction were drawn. RESULTS: The patient group showed a notably higher lncRNA ZFAS1 level than the control group (P<0.001), and the area under the receiver operating characteristic (ROC) of lncRNA ZFAS1 in diagnosing LDD was 0.807. In addition, after therapy, the patient group showed a remarkable decrease in serum lncRNA ZFAS1 (P<0.01). Serum lncRNA ZFAS1 was positively correlated with serum TNF-α, IL-6 and IL-1ß in patients (all P<0.05). Moreover, serum lncRNA ZFAS1 in the good efficacy group was notably lower than that in the general efficacy group (P<0.01). Age and lncRNA ZFAS1 expression before therapy were independent risk factors for patients' prognosis (both P<0.05). CONCLUSION: LncRNA ZFAS1 is highly expressed in patients with LDD and is a potential prognostic indicator for LDD.

17.
Front Cell Dev Biol ; 9: 763875, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966741

RESUMO

Oncofetal chondroitin sulfate expression plays an important role in the development of tumors and the pathogenesis of malaria in pregnancy. However, the biosynthesis and functions of these chondroitin sulfates, particularly the tissue-specific regulation either in tumors or placenta, have not been fully elucidated. Here, by examining the glycogenes availability in chondroitin sulfate biosynthesis such as xylosytransferase, chondroitin synthase, sulfotransferase, and epimerase, the conserved or differential CS glycosylation in normal, colorectal cancer (CRC), and placenta tissue were predicted. We found that the expression of seven chondroitin sulfate biosynthetic enzymes, namely B4GALT7, B3GALT6, B3GAT3, CHSY3, CHSY1, CHPF, and CHPF2, were significantly increased, while four other enzymes (XYLT1, CHST7, CHST15, and UST) were decreased in the colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) patients. In the human placenta, where the distinct chondroitin sulfate is specifically bound with VAR2CSA on Plasmodium parasite-infected RBC, eight chondroitin sulfate biosynthesis enzymes (CSGALNACT1, CSGALNACT2, CHSY3, CHSY1, CHPF, DSE, CHST11, and CHST3) were significantly higher than the normal colon tissue. The similarly up-regulated chondroitin synthases (CHSY1, CHSY3, and CHPF) in both cancer tissue and human placenta indicate an important role of the proteoglycan CS chains length for Plasmodium falciparum VAR2CSA protein binding. Interestingly, twelve highly expressed chondroitin sulfate enzymes were significantly correlated to worse outcomes (prognosis) in both COAD and READ. Furthermore, we showed that the levels of chondroitin sulfate enzymes are significantly correlated with the expression of immuno-regulators and immune infiltration levels in CRCs and placenta, and involved in multiple essential pathways, such as extracellular matrix organization, epithelial-mesenchymal transition, and cell adhesion. Our study provides novel insights into the oncofetal chondroitin sulfate biosynthesis regulation and identifies promising targets and biomarkers of immunotherapy for CRC and malaria in pregnancy.

18.
Chin J Nat Med ; 19(12): 900-911, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34961588

RESUMO

Buxue Yimu Pill (BYP) is a classic gynecological medicine in China, which is composed of Angelica sinensis (Oliv.) Diels, Leonurus japonicus Houtt, Astragalus membranaceus (Fisch.) Bunge, Colla corii asini and Citrus reticulata Blanco. It has been widely used in clinical therapy with the function of enriching Blood, nourishing Qi, and removing blood stasis. The current study was designed to determine the bioactive molecules and therapeutic mechanism of BYP against hemorrhagic anemia. Herein, GC-MS and UPLC/Q-TOF-MS/MS were employed to identify the chemical compounds from BYP. The genecards database (https: //www.genecards.org/) was used to obtain the potential target proteins related to hemorrhagic anemia. Autodock/Vina was adopted to evaluate the binding ability of protein receptors and chemical ligands. Gene ontology and KEGG pathway enrichment analysis were conducted using the ClusterProfiler. As a result, a total of 62 candidate molecules were identified and 152 targets related to hemorrhagic anemia were obtained. Furthermore, 34 active molecules and 140 targets were obtained through the virtual screening experiment. The data of molecular-target (M-T), target-pathway (T-P), and molecular-target-pathway (M-T-P) network suggested that 32 active molecules enhanced hematopoiesis and activated the immune system by regulating 57 important targets. Pharmacological experiments showed that BYP significantly increased the counts of RBC, HGB, and HCT, and significantly down-regulated the expression of EPO, IL-6, CSF3, NOS2, VEGFA, PDGFRB, and TGFB1. The results also showed that leonurine, leonuriside B, leosibiricin, ononin, rutin, astragaloside I, riligustilide and levistolide A, were the active molecules closely related to enriching Blood. In conclusion, based on molecular docking, network pharmacology and validation experiment results, the enriching blood effect of BYP on hemorrhagic anemia may be associated with hematopoiesis, anti-inflammation, and immunity enhancement.


Assuntos
Anemia , Medicamentos de Ervas Chinesas , Anemia/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem
19.
Chin J Nat Med ; 19(12): 930-943, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34961591

RESUMO

Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg-1·d-1. In order to search for SBT targets and related metabolites, the dysregulated genes and metabolites were detected by transcriptomics and metabolomics. Immune related indicators such as interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Treg cell disorders was analyzed by flow cytometry. Our results showed that SBT significantly alleviated the symptoms of OM rats and the inflammatory infiltration of ulcer tissues. After SBT administration, inflammatory related metabolic pathways including linoleic acid metabolism, valine, leucine and isoleucine biosynthesis were significantly altered. Furthermore, the production of proinflammatory factors like IL-17 and TNF-α, were also dramatically reduced after SBT administration. Besides, the infiltration degree of Treg cells in the spleen of OM modeling rats was significantly improved by SBT administration, thus maintaining the immune balance of the body. The current study demonstrates that SBT regulates inoleic acid metabolism, glycerophospholipid metabolism and amino acid metabolism, and inhibits IL-17/TNF signal transduction to restore Treg and Th17 cell homeostasis in OM rats, thereby alleviating chemotherapy-induced OM.


Assuntos
Medicamentos de Ervas Chinesas , Estomatite , Animais , Metaboloma , Qualidade de Vida , Ratos , Comprimidos , Transcriptoma
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(5): 534-537, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34816668

RESUMO

Objective: To investigate the effects of Sitagliptin on myocardial remodeling and autophagy in diabetic mice and its possible mechanisms. Methods: C57 mice aged ten weeks were treated with streptozocin (STZ) at the dose of 50 mg/(kg·d) by intraperitoneal injections for five consecutive days, and the level of fasting blood glucose concentration was higher than 16.7 mmol/l after seven days indicated that the diabetic model was established successfully. Mice were divided into four groups, including control group (n=10) which was intraperitoneally injected with the same volum of saline, the model group (n=8), Sitagliptin treatment group(diabetic mice were treated with Sitagliptin at the dose of 10 mg/(kg·d)by gavage, n=8) and the inhibitor group(diabetic mice were treated with Compound C, an AMPK inhibitor, at the dose of 10 mg/(kg·d) by intraperitoneal injection, n=8). After six weeks, all the mices were weighted and then put to death and the hearts were separated to caculate ventricular /body weight ratio. Hemaloxylin-Eosin (HE) staining was used to observe the cell morphology and masson staining was used to observe interstitial fibrosis. Western blot was used to test the heart protein expressions of Connexin43(Cx43), adenosine 5'-monophosphate -activated protein kinase (AMPK), brain natriuretic peptide(BNP), transforming growth factor(TGF-ß) and LC3B. Results: After six weeks of treatment, compared with control group, the ventricular /body weight ratio was improved (P<0.05), The cardiomyocyte hypertrophy and increased fibrosis were observed in the model group. The expression levels of BNP and TGF-ß were increased, while the expression levels of Cx43,LC3B and AMPK were decreased significantly(P<0.05). However, compared with model group, treatment with Sitagliptin decreased BNP, TGF-ß protein levels and increased Cx43 and LC3B protein levels, while Compound C could inhibit the upregulation of Cx43, LC3B and AMPK protein (P<0.05). Conclusion: Sitagliptin could improve cardiac hypertrophy and decrease interstitial fibrosis and AMPK-related signaling pathways was involved in the regulation of Cx43 and autophagy.


Assuntos
Diabetes Mellitus Experimental , Fosfato de Sitagliptina , Animais , Autofagia , Diabetes Mellitus Experimental/tratamento farmacológico , Camundongos , Miocárdio , Fosfato de Sitagliptina/farmacologia , Estreptozocina
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