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  • 1
    Online Resource
    Online Resource
    DataSheet1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-5-10)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-5-10)
    Abstract: Phenolic acids are cardiovascular constituents (originating from the Chinese medicinal herb Salvia miltiorrhiza root/Danshen) of DanHong and many other Danshen-containing injections. Our earlier pharmacokinetic investigation of DanHong suggested that hepatic and/or renal uptake of the Danshen compounds was the crucial steps in their systemic elimination. This investigation was designed to survey the molecular basis underlying hepatobiliary and renal excretion of the Danshen compounds, i.e., protocatechuic acid, tanshinol, rosmarinic acid, salvianolic acid D, salvianolic acid A, lithospermic acid, and salvianolic acid B. A large battery of human hepatic and renal transporters were screened for transporting the Danshen compounds and then characterized for the uptake kinetics and also compared with associated rat transporters. The samples were analyzed by liquid chromatography/mass spectrometry. Because the Danshen phenolic acids are of poor or fairly good membrane permeability, their elimination via the liver or kidneys necessitates transporter-mediated hepatic or renal uptake from blood. Several human transporters were found to mediate hepatic and/or renal uptake of the Danshen compounds in a compound-molecular-mass-related manner. Lithospermic acid and salvianolic acid B (both & gt;500 Da) underwent systemic elimination, initiated by organic anion-transporting polypeptide (OATP)1B1/OATP1B3-mediated hepatic uptake. Rosmarinic acid and salvianolic acids D (350–450 Da) underwent systemic elimination, initiated by OATP1B1/OATP1B3/organic anion transporter (OAT)2-mediated hepatic uptake and by OAT1/OAT2-mediated renal uptake. Protocatechuic acid and tanshinol (both & lt;200 Da) underwent systemic elimination, initiated by OAT1/OAT2-mediated renal uptake and OAT2-mediated hepatic uptake. A similar scenario was observed with the rat orthologs. The investigation findings advance our understanding of the disposition of the Danshen phenolic acids and could facilitate pharmacokinetic research on other Danshen-containing injections.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.911982
    DOI: 10.3389/fphar.2022.911982.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 2
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    Electroacupuncture relieves hyperalgesia by regulating neuronal–glial interaction and glutamate transporters of spinal dorsal horns in rats with acute incisional neck pain
    Frontiers Media SA ; 2022
    In:  Frontiers in Neuroscience Vol. 16 ( 2022-10-26)
    Details
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-10-26)
    Abstract: Glial cells are involved in the analgesic effect of electroacupuncture (EA) in rats with chronic neurological pain. The objective of this study was to observe the role of neuronal–glial interaction and glutamate (Glu) transporters in EA-induced acute neck pain relief in rats. Materials and methods Male rats were placed into the following five groups: control, model, EA Futu (LI18), EA Hegu (LI4)-Neiguan (PC6), and EA Zusanli (ST36)-Yanglingquan (GB34). The incisional neck pain model was established by making a longitudinal incision along the midline of the neck. The thermal pain threshold (TPT) was measured using a radiation heat detector. The immunoactivities of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), neurokinin-1 receptor (NK-1R), Glu aspartate transporter (GLAST), and Glu transporter-1 (GLT-1) in the dorsal horns (DHs) of the cervico-spinal cord (C2–C5) were detected using immunofluorescence histochemistry. The expression levels of GFAP, Iba-1, GLAST, and GLT-1 mRNAs were determined using quantitative real-time polymerase chain reaction (PCR). Results The TPT and levels of mRNAs expression and immunoactivity of GLT-1 and GLAST were significantly decreased, and those of Iba-1 and GFAP were significantly increased in the model group than those of the control group ( P & lt; 0.05). The activated microgliacytes were gathered around the NK-1R positive neurons, and co-expression of NK-1R and astrocytes was observed in the model group. EA LI18 significantly increased the TPT and expression of GLAST and GLT-1 mRNAs ( P & lt; 0.05) and notably decreased the number of Iba-1 positive cells and Iba-l mRNA expression ( P & lt; 0.05), whereas GLAST and GLT-1 antagonists inhibited the analgesic effect of EA LI18. However, these effects, except for the downregulation of Iba-1 mRNA, were not observed in the EA ST36-GB34 group. Fewer NK-1R-positive neurons were visible in the spinal DHs in the EA LI18 group, and the co-expression of NK-1R and astrocytes was also lower than that in the three EA groups. Conclusion Electroacupuncture of LI18 had an analgesic effect in rats with neck incisions, which may be related to its functions in suppressing the neuronal–glial cell interaction through NK-1R and upregulating the expression of GLAST and GLT-1 in the spinal DHs.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    URL: Article
    DOI: 10.3389/fnins.2022.885107
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2411902-7
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  • 3
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    Table_9.xls
    Frontiers Media SA ; 2022
    In:  Frontiers in Plant Science Vol. 13 ( 2022-11-10)
    Details
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 13 ( 2022-11-10)
    Abstract: Red sage, the dry root and rhizome of the herbaceous plant Salvia miltiorrhiza Bunge, is widely used for treating various diseases. The low content of tanshinones (terpenoids) has always restricted development of the S. miltiorrhiza industry. Here, we found that SmDXS5 , a rate-limiting enzyme-coding gene located at the intersection of primary and secondary metabolism, can effectively change the transcription level and secondary metabolome profile of hairy roots of S. miltiorrhiza , and significantly increase the content of tanshinones. Agrobacterium rhizogenes was used to infuse S. miltiorrhiza explants, and hairy roots of S. miltiorrhiza expressing the SmDXS5 gene were obtained successfully. We identified 39 differentially accumulated metabolites (DAMs) by metabolomics based on ultra-high performance liquid chromatography quadrupole exactive mass spectrometry and multivariate statistics. These DAMs might be key metabolites of SmDXS5 gene regulation. RNA sequencing was used to compare gene expression between the hairy roots of the SmDXS5 overexpressing group and the blank control (BC) group. Compared with the BC group, 18,646 differentially expressed genes were obtained: 8994 were upregulated and 9,652 downregulated. The combined transcriptome and metabolome analyses revealed that the mevalonate and methylerythritol phosphate pathways and synthase gene expression levels in the SmDXS5 overexpressing group were upregulated significantly, and the accumulation of tanshinone components was increased significantly, which promoted the process of glycolysis and promoted the transformation of carbohydrates to secondary metabolism. Moreover, the expression of SmPAL , the first rate-limiting enzyme gene of the phenylpropane pathway, decreased, reducing the accumulation of phenolic acid, another secondary metabolite. Therefore, SmDXS5 can be defined as a ‘valve’ gene, mainly responsible for regulating the distribution of primary and secondary metabolic flow of tanshinones in S. miltiorrhiza , and for other secondary metabolic pathways. The discovery of SmDXS5 and its molecular valve function in regulating primary and secondary metabolism will provide a basis for the industrial production of tanshinone components, and cultivation of high quality S. miltiorrhiza .
    Type of Medium: Online Resource
    ISSN: 1664-462X
    URL: Article
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    DOI: 10.3389/fpls.2022.1043761
    DOI: 10.3389/fpls.2022.1043761.s001
    DOI: 10.3389/fpls.2022.1043761.s002
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    DOI: 10.3389/fpls.2022.1043761.s021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 4
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    Table_3.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-6-30)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-6-30)
    Abstract: To use machine learning methods to explore overall survival (OS)-related prognostic factors in elderly multiple myeloma (MM) patients. Methods Data were cleaned and imputed using simple imputation methods. Two data resampling methods were implemented to facilitate model building and cross validation. Four algorithms including the cox proportional hazards model (CPH); DeepSurv; DeepHit; and the random survival forest (RSF) were applied to incorporate 30 parameters, such as baseline data, genetic abnormalities and treatment options, to construct a prognostic model for OS prediction in 338 elderly MM patients ( & gt;65 years old) from four hospitals in Beijing. The C-index and the integrated Brier score (IBwere used to evaluate model performances. Results The 30 variables incorporated in the models comprised MM baseline data, induction treatment data and maintenance therapy data. The variable importance test showed that the OS predictions were largely affected by the maintenance schema variable. Visualizing the survival curves by maintenance schema, we realized that the immunomodulator group had the best survival rate. C-indexes of 0.769, 0.780, 0.785, 0.798 and IBS score of 0.142, 0.112, 0.108, 0.099 were obtained from the CPH model, DeepSurv, DeepHit, and the RSF model respectively. The RSF model yield best scores from the fivefold cross-validation, and the results showed that different data resampling methods did affect our model results. Conclusion We established an OS model for elderly MM patients without genomic data based on 30 characteristics and treatment data by machine learning.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.922039
    DOI: 10.3389/fonc.2022.922039.s001
    DOI: 10.3389/fonc.2022.922039.s002
    DOI: 10.3389/fonc.2022.922039.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 5
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    Associations of multiple visual rating scales based on structural magnetic resonance imaging with disease severity and cerebrospinal fluid biomarkers in patients with Alzheimer’s disease
    Frontiers Media SA ; 2022
    In:  Frontiers in Aging Neuroscience Vol. 14 ( 2022-7-29)
    Details
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 14 ( 2022-7-29)
    Abstract: The relationships between multiple visual rating scales based on structural magnetic resonance imaging (sMRI) with disease severity and cerebrospinal fluid (CSF) biomarkers in patients with Alzheimer’s disease (AD) were ambiguous. In this study, a total of 438 patients with clinically diagnosed AD were recruited. All participants underwent brain sMRI scan, and medial temporal lobe atrophy (MTA), posterior atrophy (PA), global cerebral atrophy-frontal sub-scale (GCA-F), and Fazekas rating scores were visually evaluated. Meanwhile, disease severity was assessed by neuropsychological tests such as the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating (CDR). Among them, 95 patients were tested for CSF core biomarkers, including Aβ 1–42 , Aβ 1–40 , Aβ 1–42/ Aβ 1–40 , p-tau, and t-tau. As a result, the GCA-F and Fazekas scales showed positively significant correlations with onset age ( r = 0.181, p & lt; 0.001; r = 0.411, p & lt; 0.001, respectively). Patients with late-onset AD (LOAD) showed higher GCA-F and Fazekas scores ( p & lt; 0.001, p & lt; 0.001). With regard to the disease duration, the MTA and GCA-F were positively correlated ( r = 0.137, p & lt; 0.05; r = 0.106, p & lt; 0.05, respectively). In terms of disease severity, a positively significant association emerged between disease severity and the MTA, PA GCA-F, and Fazekas scores ( p & lt; 0.001, p & lt; 0.001, p & lt; 0.001, p & lt; 0.05, respectively). Moreover, after adjusting for age, gender, and APOE alleles, the MTA scale contributed to moderate to severe AD in statistical significance independently by multivariate logistic regression analysis ( p & lt; 0.05). The model combining visual rating scales, age, gender, and APOE alleles showed the best performance for the prediction of moderate to severe AD significantly (AUC = 0.712, sensitivity = 51.5%, specificity = 84.6%). In addition, we observed that the MTA and Fazekas scores were associated with a lower concentration of Aβ 1–42 ( p & lt; 0.031, p & lt; 0.022, respectively). In summary, we systematically analyzed the benefits of multiple visual rating scales in predicting the clinical status of AD. The visual rating scales combined with age, gender, and APOE alleles showed best performance in predicting the severity of AD. MRI biomarkers in combination with CSF biomarkers can be used in clinical practice.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    DOI: 10.3389/fnagi.2022.906519
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2558898-9
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  • 6
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    Protective Efficacy Against Acute and Chronic Toxoplasma gondii Infection Induced by Immunization With the DNA Vaccine TgDOC2C
    Frontiers Media SA ; 2018
    In:  Frontiers in Microbiology Vol. 9 ( 2018-12-4)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 9 ( 2018-12-4)
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    DOI: 10.3389/fmicb.2018.02965
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2587354-4
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  • 7
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    Research on the Histological Features and Pathological Types of Gastric Adenocarcinoma With Mucinous Differentiation
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-3-4)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-3-4)
    Abstract: To discuss the histological features, pathological types, and prognosis of gastric adenocarcinoma with mucinous differentiation. Methods Specimens of 189 cases of gastric adenocarcinoma with mucinous differentiation were collected for detailed histomorphology, immunohistochemistry, fluorescence in situ hybridization, and follow-up. Results In accordance with the morphological and histological structural features of the cancer cells as well as the area ratio of the mucus, gastric adenocarcinoma with mucinous differentiation was divided into four types, namely pure mucinous carcinoma, intraductal papillary mucinous carcinoma, signet ring cell type mucinous carcinoma, and mixed cell type mucinous carcinoma. Based on the macroscopic types according to Bormann's classification, pure mucinous carcinoma was mostly Type I, intraductal papillary mucinous carcinoma was mostly Type II, signet ring cell type mucinous carcinoma was mostly Type IV, and mixed cell type mucinous carcinoma was mostly Type III. The 5-year survival rate was 69.2, 64.2, 0, and 31.5%, respectively. There was a statistical difference in the lymph node metastasis rate and survival rate of the four carcinoma types. The invasion features of pure mucinous carcinoma entailed penetrating corrosively in a push-in form, without blood vessel or lymphatic metastasis and with few lymphocytes and lymphatic nodules in the marginal area. Thus, there was little lymph node metastasis and invasion of nerves. The HER2 protein expression rate was 40.2% (76/189), the HER2 gene amplification detected by FISH technology was 16.9% (32/189). Conclusion The independent histological type, four subtypes, and histopathological classification of gastric mucinous adenocarcinoma are important for the prognosis evaluation and precise treatment of this disease.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2022.829702
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 8
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    The Histopathological Types and Distribution Characteristics of Gastric Mixed Tumors
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-6-17)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-6-17)
    Abstract: The present study aimed to investigate the histopathological types and distribution characteristics of gastric mixed tumors. Methods Detailed histological observations, together with related immunohistochemical and genetic tests, were analyzed on 960 surgically resected samples in 6 hospitals with gastric mixed tumors from May 2017 to May 2021 in this retrospective study. Results Epithelial-derived tumors accounted for 80.10% (769/960) of the gastric mixed tumor samples studied, and tumors of different tissue origins accounting for 10.83% (104/960), mesenchymal-derived tumors accounting for 6.25% (60/960), neuroendocrine tumors accounting for 2.40% (23/960), and lymphoma accounting for 0.42% (4/960). The histological types of gastric mixed tumors identified as most commonly were epithelial originated, followed by mixed tumors of different tissue originated, then mixed neuroendocrine, lymphoma, and mesenchymal originated in sequence. The histological number of gastric mixed tumors was ≤ 3 in 83.23% (799/960) of cases and & gt; 4 in 16.77% (161/960) of cases. The mixed histological patterns of gastric mixed tumors were divided into three types: those with tumor cells interspersed with each other, those with incomplete fibrous tissue separation, and those without fibrous tissue separation. The gene target characteristics of gastric mixed tumors were the existence of multi-gene mutation, including human epidermalgrowth factor receptor-2 (HER2) gene amplification, key result areas (K-ras) and platelet-derived growth factor receptor alpha (PDGFRA). Conclusion Gastric mixed tumors should be adequately sampled, each piece of tissue should be involved in the morphological proportional division of the tumor, and any independent histological component should be written into the pathological examination report.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2022.873005
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 9
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    Image2.TIF
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-6-13)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-6-13)
    Abstract: Objective: Dacomitinib has been approved for non-small-cell lung cancer (NSCLC) patients harboring classical epidermal growth factor receptor ( EGFR ) mutations; however, clinical evidence of its activity on major uncommon EGFR mutations is currently limited. Materials and methods: This was a dual-center, single-arm, ambispective cohort study in China. Patients with histologically confirmed metastatic or recurrent NSCLC harboring major uncommon EGFR mutations were eligible for the study. The objective response rate and disease control rate were determined by RECIST 1.1 every 1–2 months. Adverse events were assessed by CTCAE 5.0. Results: In total, 32 NSCLC patients were enrolled between July 2020 and January 2022, and 18 (56.3%) patients received dacomitinib as first-line therapy. Median age was 64 years, and 20 (62.5%) were female. The mutations identified were G719X ( n = 24; 75%), followed by L861X ( n = 10; 31.3%), and S768I ( n = 8; 25%). In the first-line setting, 72.2% of patients (13/18) had a confirmed partial response and 100% (18/18) had disease control, and the median progression-free survival (PFS) and overall survival (OS) were unreached. In the whole cohort, 56.3% of patients (18/32) had a confirmed partial response and 90.6% (29/32) had disease control, and the median PFS was 10.3 months (95% confidence interval, 6.1–14.5) and the median OS was 36.5 months. Except for one case not available for brain re-evaluation, control of the intracranial metastases was observed in 13 patients (13/14, 92.9%). No grade 4–5 adverse events (AEs) occurred, but all patients had grade 1–2 AEs, and 12.5% (4/32) patients required a dosage reduction due to intolerable AEs. Conclusions: Dacomitinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring major uncommon EGFR mutations.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.919652
    DOI: 10.3389/fphar.2022.919652.s001
    DOI: 10.3389/fphar.2022.919652.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 10
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    Changes in Serum Neutralizing Antibodies Levels During Convalescence of COVID-19 Patients
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-2-11)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-2-11)
    Abstract: Detection of serum-specific SARS-CoV-2 antibody has become a complementary means for the identification of coronavirus disease 2019 (COVID-19). As we already know, the neutralizing antibody titers in patients with COVID-19 decrease during the course of time after convalescence, whereas the duration of antibody responses in the convalescent patients has not been defined clearly. In the current study, we collected 148 serum samples from 37 confirmed COVID-19 cases with different disease severities. The neutralizing antibodies (Nabs), IgM and IgG against COVID-19 were determined by CLIA Microparticle and microneutralization assay, respectively. The time duration of serum titers of SARS-CoV-2 antibodies were recorded. Our results indicate that IgG (94.44%) and Nabs (89.19%) can be detected at low levels within 190–266 days of disease onset. The findings can advance knowledge regarding the antibody detection results for COVID-19 patients and provide a method for evaluating the immune response after vaccination.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2022.829273
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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