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  • MDPI AG  (144)
  • 1
    Online Resource
    Online Resource
    Characterization of Estrogen Receptors in Pancreatic Adenocarcinoma with Tertiary Lymphoid Structures
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 3 ( 2023-01-29), p. 828-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 3 ( 2023-01-29), p. 828-
    Abstract: The role of estrogen signaling in antitumor immunology remains unknown for non-traditional sex-biased cancer types such as pancreatic adenocarcinoma (PAAD). Tertiary lymphoid structures (TLS) are active zones composed of multiple types of immune cells, whose presence indicates anti-tumor immune responses. In this study, we employed a 12-chemokine signature to characterize potential gene categories associated with TLS development and identified seventeen major gene categories including estrogen receptors (ERs). Immunohistochemistry staining revealed the expression patterns of three ERs (ERα, ERβ, and GPER) in 174 PAAD samples, and their correlation with clinicopathological characteristics, immune cell infiltration levels, and intratumoral TLS presence was analyzed. The results indicated that ERα (+) and ERβ (+) were correlated with high tumor grade, and ERβ (+) and GPER (+) were correlated with lower TNM stage, and both ERα (+) and GPER (+) displayed a beneficial effect on prognosis in this cohort. Interestingly, positive staining of all three ERs was significantly correlated with the presence of intratumoral TLSs and infiltration of more active immune cells into the microenvironment. Moreover, the chemotaxis of CD8+T-cells to PAAD cells was significantly increased in vitro with upregulated expression of ERα or ERβ on PAAD cells. To conclude, our study showed a novel correlation between ER expression and TLS development, suggesting that ERs may play a protective role by enhancing anti-tumor immune responses in PAAD.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15030828
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 2
    Online Resource
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    Expression Profiles of Cuproptosis-Related Genes Determine Distinct Subtypes of Pancreatic Ductal Adenocarcinoma
    MDPI AG ; 2023
    In:  Current Oncology Vol. 30, No. 2 ( 2023-01-29), p. 1648-1662
    Details
    In: Current Oncology, MDPI AG, Vol. 30, No. 2 ( 2023-01-29), p. 1648-1662
    Abstract: Background: Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent subtype of pancreatic cancer and one of the most malignant tumors worldwide. Due to the heterogeneity of its genomics and proteomics, the prognosis of PDAC remains disappointing despite advances in surgery and medicines. Recently, a novel form of programmed cell death, cuproptosis, was proposed, although its role in PDAC has not been investigated. This study aimed to quantify the expression of cuproptosis-related genes and characterize the novel subtypes of PDAC. Methods: To evaluate the pattern of cuproptosis in PDAC, the gene expression data and clinical information of 372 samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A consensus cluster analysis was performed using the transcriptional levels, genetic alterations, and individual prognostic values of seven pre-selected cuproptosis-related genes (DLAT, LIPT1, FDX1, DLD, PDHB, PDHA1, and LIAS) to identify the novel subtypes associated with cuproptosis in PDAC. A univariate Cox regression analysis was used to determine the significant prognostic indicators and cuproptosis scores among the differentially expressed genes (DEGs) between the dividing subclusters, followed by a principal component analysis. The prognostic values, immune profiles, treatment sensitivities, and cuproptosis scores were evaluated between the different subgroups. Results: Seven cuproptosis-related genes showed aberrant expression levels and genetic alterations in the PDAC tumor microenvironment. Among them, LIPT1, LIAS, DLAT, PDHA1, and DLD were significantly correlated with overall survival. Based on the expression profiles of the seven cuproptosis-related genes, three cuproptosis clusters (Clusters A, B, and C) were identified, which were represented by different clinicopathologic features, gene expression levels, and biological processes. A total of 686 DEGs were identified among the three cuproptosis clusters, of which 35 prognosis-related DEGs were selected to further classify the PDAC samples into two subgroups with different survival rates, clinicopathologic features, immune infiltration levels, and drug sensitivities. Higher cuproptosis scores were associated with a significantly poorer prognosis. Conclusion: The cuproptosis subtypes, scores, and relevant genes represent valuable information for assessing the heterogeneity, treatment, and prognosis of PDAC.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    URL: Article
    DOI: 10.3390/curroncol30020126
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2270777-3
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  • 3
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    Cervical Secretion Methylation Is Associated with the Pregnancy Outcome of Frozen-Thawed Embryo Transfer
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 2 ( 2023-01-15), p. 1726-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 2 ( 2023-01-15), p. 1726-
    Abstract: The causes of implantation failure remain a black box in reproductive medicine. The exact mechanism behind the regulation of endometrial receptivity is still unknown. Epigenetic modifications influence gene expression patterns and may alter the receptivity of human endometrium. Cervical secretions contain endometrial genetic material, which can be used as an indicator of the endometrial condition. This study evaluates the association between the cervical secretion gene methylation profile and pregnancy outcome in a frozen-thawed embryonic transfer (FET) cycle. Cervical secretions were collected from women who entered the FET cycle with a blastocyst transfer (36 pregnant and 36 non-pregnant women). The DNA methylation profiles of six candidate genes selected from the literature review were measured by quantitative methylation-specific PCR (qMSP). Bioinformatic analysis of six selected candidate genes showed significant differences in DNA methylation between receptive and pre-receptive endometrium. All candidate genes showed different degrees of correlation with the pregnancy outcomes in the logistic regression model. A machine learning approach showed that the combination of candidate genes’ DNA methylation profiles could differentiate pregnant from non-pregnant samples with an accuracy as high as 86.67% and an AUC of 0.81. This study demonstrated the association between cervical secretion methylation profiles and pregnancy outcomes in an FET cycle and provides a basis for potential clinical application as a non-invasive method for implantation prediction.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24021726
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
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    pH Mapping of Skeletal Muscle by Chemical Exchange Saturation Transfer (CEST) Imaging
    MDPI AG ; 2020
    In:  Cells Vol. 9, No. 12 ( 2020-12-04), p. 2610-
    Details
    In: Cells, MDPI AG, Vol. 9, No. 12 ( 2020-12-04), p. 2610-
    Abstract: Magnetic resonance imaging (MRI) is extensively used in clinical and basic biomedical research. However, MRI detection of pH changes still poses a technical challenge. Chemical exchange saturation transfer (CEST) imaging is a possible solution to this problem. Using saturation transfer, alterations in the exchange rates between the solute and water protons because of small pH changes can be detected with greater sensitivity. In this study, we examined a fatigued skeletal muscle model in electrically stimulated mice. The measured CEST signal ratio was between 1.96 ppm and 2.6 ppm in the z-spectrum, and this was associated with pH values based on the ratio between the creatine (Cr) and the phosphocreatine (PCr). The CEST results demonstrated a significant contrast change at the electrical stimulation site. Moreover, the pH value was observed to decrease from 7.23 to 7.15 within 20 h after electrical stimulation. This pH decrease was verified by 31P magnetic resonance spectroscopy and behavioral tests, which showed a consistent variation over time.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells9122610
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661518-6
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  • 5
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    DNA Methylation of Window of Implantation Genes in Cervical Secretions Predicts Ongoing Pregnancy in Infertility Treatment
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 6 ( 2023-03-15), p. 5598-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 6 ( 2023-03-15), p. 5598-
    Abstract: Window of implantation (WOI) genes have been comprehensively identified at the single cell level. DNA methylation changes in cervical secretions are associated with in vitro fertilization embryo transfer (IVF-ET) outcomes. Using a machine learning (ML) approach, we aimed to determine which methylation changes in WOI genes from cervical secretions best predict ongoing pregnancy during embryo transfer. A total of 2708 promoter probes were extracted from mid-secretory phase cervical secretion methylomic profiles for 158 WOI genes, and 152 differentially methylated probes (DMPs) were selected. Fifteen DMPs in 14 genes (BMP2, CTSA, DEFB1, GRN, MTF1, SERPINE1, SERPINE2, SFRP1, STAT3, TAGLN2, TCF4, THBS1, ZBTB20, ZNF292) were identified as the most relevant to ongoing pregnancy status. These 15 DMPs yielded accuracy rates of 83.53%, 85.26%, 85.78%, and 76.44%, and areas under the receiver operating characteristic curves (AUCs) of 0.90, 0.91, 0.89, and 0.86 for prediction by random forest (RF), naïve Bayes (NB), support vector machine (SVM), and k-nearest neighbors (KNN), respectively. SERPINE1, SERPINE2, and TAGLN2 maintained their methylation difference trends in an independent set of cervical secretion samples, resulting in accuracy rates of 71.46%, 80.06%, 80.72%, and 80.68%, and AUCs of 0.79, 0.84, 0.83, and 0.82 for prediction by RF, NB, SVM, and KNN, respectively. Our findings demonstrate that methylation changes in WOI genes detected noninvasively from cervical secretions are potential markers for predicting IVF-ET outcomes. Further studies of cervical secretion of DNA methylation markers may provide a novel approach for precision embryo transfer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24065598
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
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    Variations in Essential Oil Yield, Composition, and Antioxidant Activity of Different Plant Organs from Blumea balsamifera (L.) DC. at Different Growth Times
    MDPI AG ; 2016
    In:  Molecules Vol. 21, No. 8 ( 2016-08-05), p. 1024-
    Details
    In: Molecules, MDPI AG, Vol. 21, No. 8 ( 2016-08-05), p. 1024-
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules21081024
    Language: English
    Publisher: MDPI AG
    Publication Date: 2016
    detail.hit.zdb_id: 2008644-1
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  • 7
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    Investigation of Flexible Arrayed Lactate Biosensor Based on Copper Doped Zinc Oxide Films Modified by Iron–Platinum Nanoparticles
    MDPI AG ; 2021
    In:  Polymers Vol. 13, No. 13 ( 2021-06-23), p. 2062-
    Details
    In: Polymers, MDPI AG, Vol. 13, No. 13 ( 2021-06-23), p. 2062-
    Abstract: Potentiometric biosensors based on flexible arrayed silver paste electrode and copper-doped zinc oxide sensing film modified by iron-platinum nanoparticles (FePt NPs) are designed and manufactured to detect lactate in human. The sensing film is made of copper-doped zinc oxide (CZO) by a radio frequency (RF) sputtering system, and then modified by iron-platinum nanoparticles (FePt NPs). The surface morphology of copper-doped zinc oxide (CZO) is analyzed by scanning electron microscope (SEM). FePt NPs are analyzed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The average sensitivity, response time, and interference effect of the lactate biosensors are analyzed by voltage-time (V-T) measurement system. The electrochemical impedance is analyzed by electrochemical impedance spectroscopy (EIS). The average sensitivity and linearity over the concentration range 0.2–5 mM are 25.32 mV/mM and 0.977 mV/mM, respectively. The response time of the lactate biosensor is 16 s, with excellent selectivity.
    Type of Medium: Online Resource
    ISSN: 2073-4360
    URL: Article
    DOI: 10.3390/polym13132062
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527146-5
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  • 8
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    Physical, Chemical, and Biological Properties of Chitosan-Coated Alginate Microparticles Loaded with Porcine Interleukin-1β: A Potential Protein Adjuvant Delivery System
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 17 ( 2022-09-01), p. 9959-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 17 ( 2022-09-01), p. 9959-
    Abstract: We previously developed chicken interleukin-1β (IL-1β) mutants as single-dose adjuvants that induce protective immunity when co-administered with an avian vaccine. However, livestock such as pigs may require a vaccine adjuvant delivery system that provides long-lasting protection to reduce the need for successive booster doses. Therefore, we developed chitosan-coated alginate microparticles as a carrier for bovine serum albumin (BSA) or porcine IL-1β (pIL-1β) and assessed their physical, chemical, and biological properties. Electrospraying of the BSA-loaded alginate microparticles (BSA/ALG MPs) resulted in an encapsulation efficiency of 50%, and those MPs were then coated with chitosan (BSA/ALG/CHI MPs). Optical and scanning electron microscopy, zeta potential analysis, and Fourier transform infrared spectroscopy were used to characterize these MPs. The BSA encapsulation parameters were applied to ALG/CHI MPs loaded with pIL-1β, which were not cytotoxic to porcine fibroblasts but had enhanced bio-activity over unencapsulated pIL-1β. The chitosan layer of the BSA/ALG/CHI MPs prevented burst release and facilitated sustained release of pIL-1β for at least 28 days. In conclusion, BSA/ALG/CHI MPs prepared as a carrier for pIL-1β may be used as an adjuvant for the formulation of pig vaccines.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23179959
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 9
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    Association between Mean Arterial Pressure during the First 24 Hours and Clinical Outcome in Critically Ill Stroke Patients: An Analysis of the MIMIC-III Database
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 4 ( 2023-02-16), p. 1556-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 4 ( 2023-02-16), p. 1556-
    Abstract: Abnormal blood pressure is common in critically ill stroke patients. However, the association between mean arterial pressure (MAP) and mortality of critically ill stroke patients remains unclear. We extracted eligible acute stroke patients from the MIMIC-III database. The patients were divided into three groups: a low MAP group (MAP ≤ 70 mmHg), a normal MAP group (70 mmHg 〈 MAP ≤ 90 mmHg), and a high MAP group (MAP 〉 90 mmHg). The Cox proportional hazards model and restricted cubic splines were used to assess the association between MAP and mortality. Sensitivity analyses were conducted to investigate whether MAP had different effects on mortality in different subpopulations. A total of 2885 stroke patients were included in this study. The crude 7-day and 28-day mortality was significantly higher in the low MAP group than that in the normal MAP group. By contrast, patients in the high MAP group did not have higher crude 7-day and 28-day mortality than those in the normal MAP group. After multiple adjustments using the Cox regression model, patients with low MAP were consistently associated with higher 7-day and 28-day mortality than those with normal MAP in the following subgroups: age 〉 60 years, male, those with or without hypertension, those without diabetes, and those without CHD (p 〈 0.05), but patients with high MAP were not necessarily associated with higher 7-day and 28-day mortality after adjustments (most p 〉 0.05). Using the restricted cubic splines, an approximately L-shaped relationship was established between MAP and the 7-day and 28-day mortality in acute stroke patients. The findings were robust to multiple sensitivity analyses in stroke patients. In critically ill stroke patients, a low MAP significantly increased the 7-day and 28-day mortality, while a high MAP did not, suggesting that a low MAP is more harmful than a high MAP in critically ill stroke patients.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12041556
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 10
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    A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury Therapy
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 9 ( 2022-05-06), p. 2967-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 9 ( 2022-05-06), p. 2967-
    Abstract: Excessive inflammatory reaction aggravates brain injury and hinders the recovery of neural function in nervous system diseases. Microglia, as the major players of neuroinflammation, control the progress of the disease. There is an urgent need for effective non-invasive therapy to treat neuroinflammation mediated by microglia. However, the lack of specificity of anti-inflammatory agents and insufficient drug dose penetrating into the brain lesion area are the main problems. Here, we evaluated a series of calixarenes and found that among them the self-assembling architecture of amphiphilic sulfonatocalix[8]arene (SC8A12C) had the most potent ability to suppress neuroinflammation in vitro and in vivo. Moreover, SC8A12C assemblies were internalized into microglia through macropinocytosis. In addition, after applying the SC8A12C assemblies to the exposed brain tissue, we observed that SC8A12C assemblies penetrated into the brain parenchyma and eliminated the inflammatory factor storm, thereby restoring neurobiological functions in a mouse model of traumatic brain injury.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27092967
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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