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  • 1
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    Characterization of the Gut Microbiome in Healthy Dogs and Dogs with Diabetes Mellitus
    MDPI AG ; 2023
    In:  Animals Vol. 13, No. 15 ( 2023-08-01), p. 2479-
    Details
    In: Animals, MDPI AG, Vol. 13, No. 15 ( 2023-08-01), p. 2479-
    Abstract: With a close pathogenetic resemblance to human diabetes, canine Diabetes Mellitus, a chronic metabolic disease featuring abnormally high blood sugar levels, is increasing in prevalence worldwide. Unlike humans, canine glycemic control requires life-long insulin injections and dietary control in most cases, thereby jeopardizing diabetic dogs’ quality of life and increasing the difficulty of disease control. While many research studies have focused on elucidating the relationship between the canine gut microbiome and diseases, there is currently no research on the subject of diabetes mellitus in dogs. We hypothesized that the gut microbiome of canines with diabetes mellitus is different from that of healthy controls. Thus, we performed targeted 16S rRNA sequencing and comprehensive bioinformatic analysis to compare the gut microbiome profiles of 16 diabetic dogs with those of 32 healthy dogs. Clostridioides difficile, Phocaeicola plebeius, Lacrimispora indolis, and Butyricicoccus pullicaecorum were found to be enriched in diabetic dogs. A distinct shift towards carbohydrate degradation metabolic pathways was found to be differentially abundant in the diabetic subjects. Alteration of the co-occurrence network was also evident in the diabetic group. In conclusion, our study suggests that the gut microbial landscape differs in diabetic canines at the genera, species, functional, and network levels. These findings have significant implications for disease management, and thus warrant further research.
    Type of Medium: Online Resource
    ISSN: 2076-2615
    URL: Article
    DOI: 10.3390/ani13152479
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2606558-7
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  • 2
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    Primary Tumor Radiomic Model for Identifying Extrahepatic Metastasis of Hepatocellular Carcinoma Based on Contrast Enhanced Computed Tomography
    MDPI AG ; 2022
    In:  Diagnostics Vol. 13, No. 1 ( 2022-12-29), p. 102-
    Details
    In: Diagnostics, MDPI AG, Vol. 13, No. 1 ( 2022-12-29), p. 102-
    Abstract: This study aimed to identify radiomic features of primary tumor and develop a model for indicating extrahepatic metastasis of hepatocellular carcinoma (HCC). Contrast-enhanced computed tomographic (CT) images of 177 HCC cases, including 26 metastatic (MET) and 151 non-metastatic (non-MET), were retrospectively collected and analyzed. For each case, 851 radiomic features, which quantify shape, intensity, texture, and heterogeneity within the segmented volume of the largest HCC tumor in arterial phase, were extracted using Pyradiomics. The dataset was randomly split into training and test sets. Synthetic Minority Oversampling Technique (SMOTE) was performed to augment the training set to 145 MET and 145 non-MET cases. The test set consists of six MET and six non-MET cases. The external validation set is comprised of 20 MET and 25 non-MET cases collected from an independent clinical unit. Logistic regression and support vector machine (SVM) models were identified based on the features selected using the stepwise forward method while the deep convolution neural network, visual geometry group 16 (VGG16), was trained using CT images directly. Grey-level size zone matrix (GLSZM) features constitute four of eight selected predictors of metastasis due to their perceptiveness to the tumor heterogeneity. The radiomic logistic regression model yielded an area under receiver operating characteristic curve (AUROC) of 0.944 on the test set and an AUROC of 0.744 on the external validation set. Logistic regression revealed no significant difference with SVM in the performance and outperformed VGG16 significantly. As extrahepatic metastasis workups, such as chest CT and bone scintigraphy, are standard but exhaustive, radiomic model facilitates a cost-effective method for stratifying HCC patients into eligibility groups of these workups.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics13010102
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662336-5
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  • 3
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    Circulating Tumor Cell Enumeration for Serial Monitoring of Treatment Outcomes for Locally Advanced Esophageal Squamous Cell Carcinoma
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 3 ( 2023-01-29), p. 832-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 3 ( 2023-01-29), p. 832-
    Abstract: We aim to reveal the clinical significance and potential usefulness of dynamic monitoring of CTCs to track therapeutic responses and improve survival for advanced ESCC patients. Peripheral blood (PB) (n = 389) and azygos vein blood (AVB) (n = 13) samplings were recruited prospectively from 88 ESCC patients undergoing curative surgery from 2017 to 2022. Longitudinal CTC enumeration was performed with epithelial (EpCAM/pan-cytokeratins/MUC1) and mesenchymal (vimentin) markers at 12 serial timepoints at any of the pre-treatment, all of the post-treatments/pre-surgery, post-surgery follow-ups for 3-year, and relapse. Longitudinal real-time CTC analysis in PB and AVB suggests more CTCs are released early at pre-surgery and 3-month post-surgery into the circulation from the CTRT group compared to the up-front surgery group. High CTC levels at pre-treatments, 1-/3-month post-surgery, unfavorable changes of CTC levels between all post-treatment/pre-surgery and 1-month or 3-month post-surgery (Hazard Ratio (HR) = 6.662, p 〈 0.001), were independent prognosticators for curative treatment. The unfavorable pre-surgery CTC status was independent prognostic and predictive for neoadjuvant treatment efficacy (HR = 3.652, p = 0.035). The aggressive CTC clusters were more frequently observed in AVB compared to PB. Its role as an independent prognosticator with relapse was first reported in ESCC (HR = 2.539, p = 0.068). CTC clusters and longitudinal CTC monitoring provide useful prognostic information and potential predictive biomarkers to help guide clinicians in improving disease management.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15030832
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 4
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    A Novel Probiotic-Based Oral Vaccine against SARS-CoV-2 Omicron Variant B.1.1.529
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 18 ( 2023-09-11), p. 13931-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 18 ( 2023-09-11), p. 13931-
    Abstract: COVID-19 pandemic, caused by the SARS-CoV-2 virus, is still affecting the entire world via the rapid emergence of new contagious variants. Vaccination remains the most effective prevention strategy for viral infection, yet not all countries have sufficient access to vaccines due to limitations in manufacturing and transportation. Thus, there is an urgent need to develop an easy-to-use, safe, and low-cost vaccination approach. Genetically modified microorganisms, especially probiotics, are now commonly recognized as attractive vehicles for delivering bioactive molecules via oral and mucosal routes. In this study, Lactobacillus casei has been selected as the oral vaccine candidate based on its’ natural immunoadjuvant properties and the ability to resist acidic gastric environment, to express antigens of SARS-CoV-2 Omicron variant B.1.1.529 with B-cell and T-cell epitopes. This newly developed vaccine, OMGVac, was shown to elicit a robust IgG systemic immune response against the spike protein of Omicron variant B.1.1.529 in Golden Syrian hamsters. No adverse effects were found throughout this study, and the overall safety was evaluated in terms of physiological and histopathological examinations of different organs harvested. In addition, this study illustrated the use of the recombinant probiotic as a live delivery vector in the initiation of systemic immunity, which shed light on the future development of next-generation vaccines to combat emerging infectious diseases.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241813931
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
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  • 5
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    Ganoderma tsugae Hepatoprotection against Exhaustive Exercise-Induced Liver Injury in Rats
    MDPI AG ; 2013
    In:  Molecules Vol. 18, No. 2 ( 2013-01-29), p. 1741-1754
    Details
    In: Molecules, MDPI AG, Vol. 18, No. 2 ( 2013-01-29), p. 1741-1754
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules18021741
    Language: English
    Publisher: MDPI AG
    Publication Date: 2013
    detail.hit.zdb_id: 2008644-1
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  • 6
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    A Rapid, Simple, Inexpensive, and Mobile Colorimetric Assay COVID-19-LAMP for Mass On-Site Screening of COVID-19
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 15 ( 2020-07-29), p. 5380-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 15 ( 2020-07-29), p. 5380-
    Abstract: To control the COVID-19 pandemic and prevent its resurgence in areas preparing for a return of economic activities, a method for a rapid, simple, and inexpensive point-of-care diagnosis and mass screening is urgently needed. We developed and evaluated a one-step colorimetric reverse-transcriptional loop-mediated isothermal amplification assay (COVID-19-LAMP) for detection of SARS-CoV-2, using SARS-CoV-2 isolate and respiratory samples from patients with COVID-19 (n = 223) and other respiratory virus infections (n = 143). The assay involves simple equipment and techniques and low cost, without the need for expensive qPCR machines, and the result, indicated by color change, is easily interpreted by naked eyes. COVID-19-LAMP can detect SARS-CoV-2 RNA with detection limit of 42 copies/reaction. Of 223 respiratory samples positive for SARS-CoV-2 by qRT-PCR, 212 and 219 were positive by COVID-19-LAMP at 60 and 90 min (sensitivities of 95.07% and 98.21%) respectively, with the highest sensitivities among nasopharyngeal swabs (96.88% and 98.96%), compared to sputum/deep throat saliva samples (94.03% and 97.02%), and throat swab samples (93.33% and 98.33%). None of the 143 samples with other respiratory viruses were positive by COVID-19-LAMP, showing 100% specificity. Samples with higher viral load showed shorter detection time, some as early as 30 min. This inexpensive, highly sensitive and specific COVID-19-LAMP assay can be useful for rapid deployment as mobile diagnostic units to resource-limiting areas for point-of-care diagnosis, and for unlimited high-throughput mass screening at borders to reduce cross-regional transmission.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21155380
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
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  • 7
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    Different Effects of Metformin and A769662 on Sodium Iodate-Induced Cytotoxicity in Retinal Pigment Epithelial Cells: Distinct Actions on Mitochondrial Fission and Respiration
    MDPI AG ; 2020
    In:  Antioxidants Vol. 9, No. 11 ( 2020-10-28), p. 1057-
    Details
    In: Antioxidants, MDPI AG, Vol. 9, No. 11 ( 2020-10-28), p. 1057-
    Abstract: Oxidative stress-associated retinal pigment epithelium (RPE) cell death is critically implicated in the pathogenesis of visual dysfunction and blindness of retinal degenerative diseases. Sodium iodate (NaIO3) is an oxidative retinotoxin and causes RPE damage. Previously, we found that NaIO3 can induce human ARPE-19 cell death via inducing mitochondrial fission and mitochondrial dysfunction. Although metformin has been demonstrated to benefit several diseases possibly via AMP-activated protein kinase (AMPK) activation, it remains unknown how AMPK affects retinopathy in NaIO3 model. Therefore, in this study, we compared the effects of metformin and AMPK activator A769662 on NaIO3-induced cellular stress and toxicity. We found that A769662 can protect cells against NaIO3-induced cytotoxicity, while metformin exerts an enhancement in cell death. The mitochondrial reactive oxygen species (ROS) production as well as mitochondrial membrane potential loss induced by NaIO3 were not altered by both agents. In addition, NaIO3-induced cytosolic ROS production, possibly from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and counteracting cell death, was not altered by A769662 and metformin. Notably, NaIO3-induced mitochondrial fission and inhibition of mitochondrial respiration for ATP turnover were reversed by A769662 but not by metformin. In agreement with the changes on mitochondrial morphology, the ERK-Akt signal axis dependent Drp-1 phosphorylation at S616 (an index of mitochondrial fission) under NaIO3 treatment was blocked by A769662, but not by metformin. In summary, NaIO3-induced cell death in ARPE cells primarily comes from mitochondrial dysfunction due to dramatic fission and inhibition of mitochondrial respiration. AMPK activation can exert a protection by restoring mitochondrial respiration and inhibition of ERK/Akt/Drp-1 phosphorylation, leading to a reduction in mitochondrial fission. However, inhibition of respiratory complex I by metformin might deteriorate mitochondrial dysfunction and cell death under NaIO3 stress.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox9111057
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2704216-9
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  • 8
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    P2X7 Is Involved in the Mouse Retinal Degeneration via the Coordinated Actions in Different Retinal Cell Types
    MDPI AG ; 2023
    In:  Antioxidants Vol. 12, No. 1 ( 2023-01-06), p. 141-
    Details
    In: Antioxidants, MDPI AG, Vol. 12, No. 1 ( 2023-01-06), p. 141-
    Abstract: Adenosine triphosphate (ATP) released from dying cells with high concentrations is sensed as a danger signal by the P2X7 receptor. Sodium iodate (NaIO3) is an oxidative toxic agent, and its retinal toxicity has been used as the model of dry age-related macular degeneration (AMD). In this study, we used NaIO3-treated mice and cultured retinal cells, including BV-2 microglia, 661W photoreceptors, rMC1 Müller cells and ARPE-19 retinal epithelial cells, to understand the pathological action of P2X7 in retinal degeneration. We found that NaIO3 can significantly decrease the photoreceptor function by reducing a-wave and b-wave amplitudes in electroretinogram (ERG) analysis. Optical coherence tomography (OCT) analysis revealed the degeneration of retinal epithelium and ganglion cell layers. Interestingly, P2X7−/− mice were protected from the NaIO3-induced retinopathy and inflammatory NLRP3, IL-1β and IL-6 gene expression in the retina. Hematoxylin and eosin staining indicated that the retinal epithelium was less deteriorated in P2X7−/− mice compared to the WT group. Although P2X7 was barely detected in 661W, rMC1 and ARPE-19 cells, its gene and protein levels can be increased after NaIO3 treatment, leading to a synergistic cytotoxicity of BzATP [2′(3′)-O-(4-benzoylbenzoyl)adenosine-5′-triphosphate tri(triethyleneammonium)salt] and NaIO3 administration in ARPE-19 cells. In conclusion, the paracrine action of the ATP/P2X7 axis via cell–cell communication is i nvolved in NaIO3-induced retinal injury. Our results show that P2X7 antagonist might be a potential therapy in inflammation-related retinal degeneration.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox12010141
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704216-9
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  • 9
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    Evaluating Teaching Effectiveness of Medical Humanities in an Integrated Clerkship Program by a Novel Prospective Propensity Score Matching Framework
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 3 ( 2022-02-08), p. 1882-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 3 ( 2022-02-08), p. 1882-
    Abstract: Background: This study aims to rigorously compare the effectiveness of the educational programs of a new integrated clinical clerkship in medicine (3 months) and surgery (3 months) at a cancer center with the conventional subspecialty-based rotations at a tertiary teaching hospital, by this prospective, pre-post comparative method. Methods: Between 2013–2016, we compared 69 students who had selected the integrated clerkship that emphasized clinical competency and medical humanities training with 138 matched peers who had completed conventional clerkships during the same period. Outcome measures for medical humanities included empathy, patient-centeredness, and other values and skills related to holistic health care professionalism by introducing prospective propensity score matching (PSM). Results: At baseline, no significant between-group differences existed. At the completion of the core clerkships, students receiving the integrative clerkship had significantly higher scores on the Patient–Practitioner Orientation Scale (PPOS) and the Professionalism Climate in Clinical Teaching Environment (PCI), and similar Jefferson Scale of Physician Empathy Student Version (JSPE) scores, as compared with the comparison group. We also found that the students in this program did not perform worse than those in the traditional internship group in the comprehensive and formative OSCE medical clinical skills test. Conclusions: Our study develops an empirical basis for rigorous evaluation to design medical education to improve the medical humanities values and skills of interns. Features of the new integrated clerkship program that we developed include substantial participation by the students in patient-centered in-hospital culture, as well as reflection, discussion, and feedback on actual clinical cases.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph19031882
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 10
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    Mechanistic Effects of Baicalein on Aqueous Humor Drainage and Intraocular Pressure
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 13 ( 2022-07-01), p. 7372-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 13 ( 2022-07-01), p. 7372-
    Abstract: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that results from impeded fluid drainage. The increase in outflow resistance is caused by trabecular meshwork (TM) cell dysfunction and excessive extracellular matrix (ECM) deposition. Baicalein (Ba) is a natural flavonoid and has been shown to regulate cell contraction, fluid secretion, and ECM remodeling in various cell types, suggesting the potential significance of regulating outflow resistance and IOP. We demonstrated that Ba significantly lowered the IOP by about 5 mmHg in living mice. Consistent with that, Ba increased the outflow facility by up to 90% in enucleated mouse eyes. The effects of Ba on cell volume regulation and contractility were examined in primary human TM (hTM) cells. We found that Ba (1–100 µM) had no effect on cell volume under iso-osmotic conditions but inhibited the regulatory volume decrease (RVD) by up to 70% under hypotonic challenge. In addition, Ba relaxed hTM cells via reduced myosin light chain (MLC) phosphorylation. Using iTRAQ-based quantitative proteomics, 47 proteins were significantly regulated in hTM cells after a 3-h Ba treatment. Ba significantly increased the expression of cathepsin B by 1.51-fold and downregulated the expression of D-dopachrome decarboxylase and pre-B-cell leukemia transcription factor-interacting protein 1 with a fold-change of 0.58 and 0.40, respectively. We suggest that a Ba-mediated increase in outflow facility is triggered by cell relaxation via MLC phosphorylation along with inhibiting RVD in hTM cells. The Ba-mediated changes in protein expression support the notion of altered ECM homeostasis, potentially contributing to a reduction of outflow resistance and thereby IOP.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23137372
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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