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  • 1
    Online Resource
    Online Resource
    Amelioration of Maternal Immune Activation-Induced Autism Relevant Behaviors by Gut Commensal Parabacteroides goldsteinii
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 21 ( 2022-10-28), p. 13070-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 21 ( 2022-10-28), p. 13070-
    Abstract: Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. Probiotics have been demonstrated to play a promising role in managing the severity of ASD. However, there are no effective probiotics for clinical use. Identifying new probiotic strains for ameliorating ASD is therefore essential. Using the maternal immune activation (MIA)-based offspring ASD-like mouse model, a probiotic-based intervention strategy was examined in female mice. The gut commensal microbe Parabacteroides goldsteinii MTS01, which was previously demonstrated to exert multiple beneficial effects on chronic inflammation-related-diseases, was evaluated. Prenatal lipopolysaccharide (LPS) exposure induced leaky gut-related inflammatory phenotypes in the colon, increased LPS activity in sera, and induced autistic-like behaviors in offspring mice. By contrast, P. goldsteinii MTS01 treatment significantly reduced intestinal and systemic inflammation and ameliorated disease development. Transcriptomic analyses of MIA offspring indicated that in the intestine, P. goldsteinii MTS01 enhanced neuropeptide-related signaling and suppressed aberrant cell proliferation and inflammatory responses. In the hippocampus, P. goldsteinii MTS01 increased ribosomal/mitochondrial and antioxidant activities and decreased glutamate receptor signaling. Together, significant ameliorative effects of P. goldsteinii MTS01 on ASD relevant behaviors in MIA offspring were identified. Therefore, P. goldsteinii MTS01 could be developed as a next-generation probiotic for ameliorating ASD.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232113070
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Rapid and Accurate Discrimination of Mycobacterium abscessus Subspecies Based on Matrix-Assisted Laser Desorption Ionization-Time of Flight Spectrum and Machine Learning Algorithms
    MDPI AG ; 2022
    In:  Biomedicines Vol. 11, No. 1 ( 2022-12-25), p. 45-
    Details
    In: Biomedicines, MDPI AG, Vol. 11, No. 1 ( 2022-12-25), p. 45-
    Abstract: Mycobacterium abscessus complex (MABC) has been reported to cause complicated infections. Subspecies identification of MABC is crucial for adequate treatment due to different antimicrobial resistance properties amid subspecies. However, long incubation days are needed for the traditional antibiotic susceptibility testing (AST). Delayed effective antibiotics administration often causes unfavorable outcomes. Thus, we proposed a novel approach to identify subspecies and potential antibiotic resistance, guiding early and accurate treatment. Subspecies of MABC isolates were determined by secA1, rpoB, and hsp65. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI–TOF MS) spectra were analyzed, and informative peaks were detected by random forest (RF) importance. Machine learning (ML) algorithms were used to build models for classifying MABC subspecies based on spectrum. The models were validated by repeated five-fold cross-validation to avoid over-fitting. In total, 102 MABC isolates (52 subspecies abscessus and 50 subspecies massiliense) were analyzed. Top informative peaks including m/z 6715, 4739, etc. were identified. RF model attained AUROC of 0.9166 (95% CI: 0.9072–0.9196) and outperformed other algorithms in discriminating abscessus from massiliense. We developed a MALDI–TOF based ML model for rapid and accurate MABC subspecies identification. Due to the significant correlation between subspecies and corresponding antibiotics resistance, this diagnostic tool guides a more precise and timelier MABC subspecies-specific treatment.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines11010045
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 3
    Online Resource
    Online Resource
    Treatment Outcome in Patients with Mycobacterium abscessus Complex Lung Disease: The Impact of Tigecycline and Amikacin
    MDPI AG ; 2022
    In:  Antibiotics Vol. 11, No. 5 ( 2022-04-25), p. 571-
    Details
    In: Antibiotics, MDPI AG, Vol. 11, No. 5 ( 2022-04-25), p. 571-
    Abstract: Background: The contemporary guidelines have recommended multiple antimicrobial therapies along with oral macrolides for the treatment of Mycobacterium abscessus complex lung disease (MABC-LD). However, there is little evidence supporting the parenteral tigecycline-containing regimens against MABC-LD. Therefore, we conducted this study to evaluate the effect of intravenous tigecycline-containing regimens on the treatment of MABC-LD. Methods: A retrospective study was conducted in 6 medical centers. Patients with MABC-LD that were followed up at ≥12 months were enrolled. Mycobacterium abscessus subspecies were identified by hsp65, rpoB, secA1 gene PCR, and sequencing. Antimicrobial susceptibility was determined for 34 patients using broth microdilution methods following the Clinical and Laboratory Standards Institute (CLSI) guideline. The microbiology and treatment outcomes were defined as either success or failure. The impacts of tigecycline and amikacin were adjusted for age, comorbidities, surgical resection, and radiologic scores. Results: During the study period, seventy-one patients were enrolled for final analysis. The microbiology failure rate was 61% (43/71) and the treatment failure rate was 62% (44/71). For M. abscessus complex, 97% (33/34) of tigecycline MIC were ≤1 mg/L. Amikacin also demonstrated great susceptibility (94.1%; 32/34). Treatment with regimens containing tigecycline plus amikacin provided better microbiology success (adjusted OR 17.724; 95% CI 1.227–267.206) and treatment success (adjusted OR 14.085; 95% CI 1.103–166.667). Conclusion: The outcome of MABC-LD is always unsatisfactory. Treatment regimens with oral macrolide in combination with tigecycline and amikacin were correlated with increased microbiology success and less treatment failure.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    URL: Article
    DOI: 10.3390/antibiotics11050571
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2681345-2
    SSG: 15,3
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  • 4
    Online Resource
    Online Resource
    Lack of Association between YEASTONE Antifungal Susceptibility Tests and Clinical Outcomes of Cryptococcus Meningitis
    MDPI AG ; 2023
    In:  Journal of Fungi Vol. 9, No. 2 ( 2023-02-10), p. 232-
    Details
    In: Journal of Fungi, MDPI AG, Vol. 9, No. 2 ( 2023-02-10), p. 232-
    Abstract: The relation between antifungal susceptibility and treatment outcomes is not well-characterized. There is paucity of surveillance data for cerebrospinal fluid (CSF) isolates of cryptococcus investigated with YEASTONE colorimetric broth microdilution susceptibility testing. A retrospective study of laboratory-confirmed cryptococcus meningitis (CM) patients was conducted. The antifungal susceptibility of CSF isolates was determined using YEASTONE colorimetric broth microdilution. Clinical parameters, CSF laboratory indices, and antifungal susceptibility results were analyzed to identify risk factors for mortality. High rates of resistance to fluconazole and flucytosine were observed in this cohort. Voriconazole had the lowest MIC (0.06 µg/mL) and lowest rate of resistance (3.8%). In a univariate analysis, hematological malignancy, concurrent cryptococcemia, high Sequential Organ Failure Assessment (SOFA) score, low Glasgow coma scale (GCS) score, low CSF glucose level, high CSF cryptococcal antigen titer, and high serum cryptococcal antigen burden were associated with mortality. In a multivariate analysis, meningitis with concurrent cryptococcemia, GCS score, and high CSF cryptococcus burden, were independent predictors of poor prognosis. Both early and late mortality rates were not significantly different between CM wild type and non-wild type species.
    Type of Medium: Online Resource
    ISSN: 2309-608X
    URL: Article
    DOI: 10.3390/jof9020232
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2784229-0
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  • 5
    Online Resource
    Online Resource
    Association between Hepatitis C Virus Infection and Esophageal Cancer: An Asian Nationwide Population-Based Cohort Study
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 11 ( 2021-05-28), p. 2395-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 11 ( 2021-05-28), p. 2395-
    Abstract: Background: Hepatitis C virus (HCV) infection causes many extrahepatic cancers, and whether HCV infection is associated with esophageal cancer development remains inconclusive. Methods: A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database (TNHIRD) was conducted. Results: From 2003 to 2012, of 11,895,993 patients, three 1:1:1 propensity score-matched cohorts, including HCV-treated (interferon-based therapy ≧6 months, n = 9047), HCV-untreated (n = 9047), and HCV-uninfected cohorts (n = 9047), were enrolled. The HCV-untreated cohort had the highest 9-year cumulative incidence of esophageal cancer among the three cohorts (0.174%; 95% confidence interval (CI): 0.068–0.395) (p = 0.0292). However, no difference in cumulative incidences was identified between the HCV-treated (0.019%; 0.002–0.109%) and HCV-uninfected cohorts (0.035%; 0.007–0.133%) (p = 0.5964). The multivariate analysis showed that HCV positivity (hazard ratio (HR): 5.1, 95% CI HR: 1.39–18.51) and male sex (HR: 8.897; 95% CI HR: 1.194–66.323) were independently associated with the development of esophageal cancer. Of the three cohorts, the HCV-untreated cohort had the highest cumulative incidence of overall mortality at 9 years (21.459%, 95% CI: 18.599–24.460) (p 〈 0.0001), and the HCV-treated (12.422%, 95% CI: 8.653–16.905%) and HCV-uninfected cohorts (5.545%, 95% CI: 4.225–7.108%) yielded indifferent cumulative mortality incidences (p = 0.1234). Conclusions: Although HCV positivity and male sex were independent factors associated with esophageal cancer development, whether HCV infection is the true culprit or a bystander for developing esophageal cancer remains to be further investigated. Interferon-based anti-HCV therapy might attenuate esophageal risk and decrease overall mortality in HCV-infected patients.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10112395
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 6
    Online Resource
    Online Resource
    Application of Drug Testing Platforms in Circulating Tumor Cells and Validation of a Patient-Derived Xenograft Mouse Model in Patient with Primary Intracranial Ependymomas with Extraneural Metastases
    MDPI AG ; 2023
    In:  Diagnostics Vol. 13, No. 7 ( 2023-03-24), p. 1232-
    Details
    In: Diagnostics, MDPI AG, Vol. 13, No. 7 ( 2023-03-24), p. 1232-
    Abstract: Primary intracranial ependymoma is a challenging tumor to treat despite the availability of multidisciplinary therapeutic modalities, including surgical resection, radiotherapy, and adjuvant chemotherapy. After the completion of initial treatment, when resistant tumor cells recur, salvage therapy needs to be carried out with a more precise strategy. Circulating tumor cells (CTCs) have specifically been detected and validated for patients with primary or recurrent diffused glioma. The CTC drug screening platform can be used to perform a mini-invasive liquid biopsy for potential drug selection. The validation of potential drugs in a patient-derived xenograft (PDX) mouse model based on the same patient can serve as a preclinical testing platform. Here, we present the application of a drug testing model in a six-year-old girl with primary ependymoma on the posterior fossa, type A (EPN-PFA). She suffered from tumor recurrence with intracranial and spinal seeding at 2 years after her first operation and extraneural metastases in the pleura, lung, mediastinum, and distant femoral bone at 4 years after initial treatment. The CTC screening platform results showed that everolimus and entrectinib could be used to decrease CTC viability. The therapeutic efficacy of these two therapeutic agents has also been validated in a PDX mouse model from the same patient, and the results showed that these two therapeutic agents significantly decreased tumor growth. After precise drug screening and the combination of focal radiation on the femoral bone with everolimus chemotherapy, the whole-body bone scan showed significant shrinkage of the metastatic tumor on the right femoral bone. This novel approach can combine liquid biopsy, CTC drug testing platforms, and PDX model validation to achieve precision medicine in rare and challenging tumors with extraneural metastases.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics13071232
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662336-5
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  • 7
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    Online Resource
    Microrna-486-5P Regulates Human Pulmonary Artery Smooth Muscle Cell Migration via Endothelin-1
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 18 ( 2022-09-08), p. 10400-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 18 ( 2022-09-08), p. 10400-
    Abstract: Pulmonary arterial hypertension (PAH) is a fatal or life-threatening disorder characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance. Abnormal vascular remodeling, including the proliferation and phenotypic modulation of pulmonary artery smooth muscle cells (PASMCs), represents the most critical pathological change during PAH development. Previous studies showed that miR-486 could reduce apoptosis in different cells; however, the role of miR-486 in PAH development or HPASMC proliferation and migration remains unclear. After 6 h of hypoxia treatment, miR-486-5p was significantly upregulated in HPASMCs. We found that miR-486-5p could upregulate the expression and secretion of ET-1. Furthermore, transfection with a miR-486-5p mimic could induce HPASMC proliferation and migration. We also found that miRNA-486-5p could downregulate the expression of SMAD2 and the phosphorylation of SMAD3. According to previous studies, the loss of SMAD3 may play an important role in miRNA-486-5p-induced HPASMC proliferation. Although the role of miRNA-486-5p in PAH in in vivo models still requires further investigation and confirmation, our findings show the potential roles and effects of miR-486-5p during PAH development.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms231810400
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
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    Antimicrobial Peptide Mastoparan-AF Kills Multi-Antibiotic Resistant Escherichia coli O157:H7 via Multiple Membrane Disruption Patterns and Likely by Adopting 3–11 Amphipathic Helices to Favor Membrane Interaction
    MDPI AG ; 2023
    In:  Membranes Vol. 13, No. 2 ( 2023-02-20), p. 251-
    Details
    In: Membranes, MDPI AG, Vol. 13, No. 2 ( 2023-02-20), p. 251-
    Abstract: We investigated the antimicrobial activity and membrane disruption modes of the antimicrobial peptide mastoparan-AF against hemolytic Escherichia coli O157:H7. Based on the physicochemical properties, mastoparan-AF may potentially adopt a 3–11 amphipathic helix-type structure, with five to seven nonpolar or hydrophobic amino acid residues forming the hydrophobic face. E. coli O157:H7 and two diarrheagenic E. coli veterinary clinical isolates, which are highly resistant to multiple antibiotics, are sensitive to mastoparan-AF, with minimum inhibitory and bactericidal concentrations (MIC and MBC) ranging from 16 to 32 μg mL−1 for E. coli O157:H7 and four to eight μg mL−1 for the latter two isolates. Mastoparan-AF treatment, which correlates proportionally with membrane permeabilization of the bacteria, may lead to abnormal dents, large perforations or full opening at apical ends (hollow tubes), vesicle budding, and membrane corrugation and invagination forming irregular pits or pores on E. coli O157:H7 surface. In addition, mRNAs of prepromastoparan-AF and prepromastoparan-B share a 5′-poly(A) leader sequence at the 5′-UTR known for the advantage in cap-independent translation. This is the first report about the 3–11 amphipathic helix structure of mastoparans to facilitate membrane interaction. Mastoparan-AF could potentially be employed to combat multiple antibiotic-resistant hemolytic E. coli O157:H7 and other pathogenic E. coli.
    Type of Medium: Online Resource
    ISSN: 2077-0375
    URL: Article
    DOI: 10.3390/membranes13020251
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2614641-1
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  • 9
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    Contribution of Testing Strategies and Contact Tracing towards COVID-19 Outbreaks Control: A Mathematical Modeling Study
    MDPI AG ; 2022
    In:  Tropical Medicine and Infectious Disease Vol. 7, No. 11 ( 2022-11-14), p. 376-
    Details
    In: Tropical Medicine and Infectious Disease, MDPI AG, Vol. 7, No. 11 ( 2022-11-14), p. 376-
    Abstract: This modeling study considers different screening strategies, contact tracing, and the severity of novel epidemic outbreaks for various population sizes, providing insight into multinational containment effectiveness of emerging infectious diseases, prior to vaccines development. During the period of the ancestral SARS-Cov-2 virus, contact tracing alone is insufficient to achieve outbreak control. Although universal testing is proposed in multiple nations, its effectiveness accompanied by other measures is rarely examined. Our research investigates the necessity of universal testing when contact tracing and symptomatic screening measures are implemented. We used a stochastic transmission model to simulate COVID-19 transmission, evaluating containment strategies via contact tracing, one-time high risk symptomatic testing, and universal testing. Despite universal testing having the potential to identify subclinical cases, which is crucial for non-pharmaceutical interventions, our model suggests that universal testing only reduces the total number of cases by 0.0009% for countries with low COVID-19 prevalence and 0.025% for countries with high COVID-19 prevalence when rigorous contact tracing and symptomatic screening are also implemented. These findings highlight the effectiveness of testing strategies and contact tracing in reducing COVID-19 cases by identifying subclinical cases.
    Type of Medium: Online Resource
    ISSN: 2414-6366
    URL: Article
    DOI: 10.3390/tropicalmed7110376
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2934690-3
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  • 10
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    Revisiting Genetic Epidemiology with a Refined Targeted Gene Panel for Hereditary Hearing Impairment in the Taiwanese Population
    MDPI AG ; 2023
    In:  Genes Vol. 14, No. 4 ( 2023-04-07), p. 880-
    Details
    In: Genes, MDPI AG, Vol. 14, No. 4 ( 2023-04-07), p. 880-
    Abstract: Hearing impairment is one of the most common sensory disorders in children, and targeted next-generation sequencing (NGS)-based genetic examinations can assist in its prognostication and management. In 2020, we developed a simplified 30-gene NGS panel from the original 214-gene NGS version based on Taiwanese genetic epidemiology data to increase the accessibility of NGS-based examinations. In this study, we evaluated the diagnostic performance of the 30-gene NGS panel and compared it with that of the original 214-gene NGS panel in patient subgroups with different clinical features. Data on the clinical features, genetic etiologies, audiological profiles, and outcomes were collected from 350 patients who underwent NGS-based genetic examinations for idiopathic bilateral sensorineural hearing impairment between 2020 and 2022. The overall diagnostic yield was 52%, with slight differences in genetic etiology between patients with different degrees of hearing impairment and ages of onset. No significant difference was found in the diagnostic yields between the two panels, regardless of clinical features, except for a lower detection rate of the 30-gene panel in the late-onset group. For patients with negative genetic results, where the causative variant is undetectable on current NGS-based methods, part of the negative results may be due to genes not covered by the panel or yet to be identified. In such cases, the hearing prognosis varies and may decline over time, necessitating appropriate follow-up and consultation. In conclusion, genetic etiologies can serve as references for refining targeted NGS panels with satisfactory diagnostic performance.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes14040880
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527218-4
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