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1.
Environ Toxicol ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38717028

ABSTRACT

Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1ß levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.

2.
Invest Ophthalmol Vis Sci ; 64(14): 25, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37975849

ABSTRACT

Purpose: This study investigated the clinical characteristics of patients with PROM1-related inherited retinal diseases (IRDs). Methods: Patients diagnosed with IRDs who had mutations in PROM1 were identified at Linkou Chang Gung Memorial Hospital and Kaohsiung Medical University Hospital in Taiwan. Information on clinical characteristics and best-corrected visual acuity was recorded. Color fundus (CF) images, fundus autofluorescence photography (FAF), spectral-domain optical coherence tomography (SD-OCT), and electroretinograms (ERGs) were analyzed to examine patient phenotypes. PROM1 variants were detected using whole exome sequencing and verified by Sanger sequencing. Results: Fourteen patients from nine families with PROM1-related IRDs were analyzed. Most patients exhibited chorioretinal atrophy in the macular area, with or without extramacular involvement on CF. Similarly, hypo-autofluorescence confined to the macular area, with or without extramacular involvement, was present for most patients on FAF. Furthermore, SD-OCT revealed outer retinal tubulations and focal or diffuse retinal thinning. ERGs showed variable findings, including maculopathy with normal ERG, subnormal cone response, and extinguished rod and cone responses. We detected five variants of the PROM1 gene, including c.139del, c.794del, c.1238T>A, c.2110C>T, and c.1117C>T. Conclusions: In this study, we evaluated 14 Taiwanese patients with five PROM1 variants. Additionally, incomplete penetrance of heterozygous PROM1 variants was observed. Furthermore, patients with autosomal dominant PROM1 variants had lesions in the macular area and the peripheral region of the retina. SD-OCT serves as a useful tool for early detection of PROM1-related IRDs, as it captures certain signs of such diseases.


Subject(s)
Macular Degeneration , Retinal Degeneration , Humans , Retina/pathology , Retinal Degeneration/genetics , Macular Degeneration/diagnosis , Retinal Cone Photoreceptor Cells , Mutation , Electroretinography , Tomography, Optical Coherence/methods , AC133 Antigen/genetics
3.
Biomedicine (Taipei) ; 13(2): 48-55, 2023.
Article in English | MEDLINE | ID: mdl-37937299

ABSTRACT

Introduction: Chemotherapy and radiation therapy for breast cancer cause side effects, such as cardiovascular changes, which can be monitored with echocardiography. However, more convenient methods are always encouraged. Radial arterial waves that are used to detect cardiovascular changes can be used to assist in confirming cardiovascular changes. Aim: This retrospective study aimed to analyze the frequency and time domains of the radial artery pulse wave in patients with breast cancer to understand its effectiveness in identifying cardiovascular changes. Methods: Patients with breast cancer were screened from the pulse examination records in Changhua Christian Hospital and divided into the treatment and remission groups. After unlinking the data, the pulse data were analyzed for the breast cancer treatment and remission group, including the average value of the parameters of four consecutive pulse diagnosis records in four consecutive months to test the difference in pulse waves due to breast cancer treatment between the two groups. Additionally, the pulse wave stability of the two groups was compared using the coefficient of variation. Results and conclusion: The comparison of the pulse wave data between 19 patients in the treatment group and 40 patients in the remission group revealed 45 parameters in time and 50 in frequency domains. D3, ND3, NA1, and NT1 are the four parameters with significant differences (p < 0.05), which are all related to heart function, and mainly related to cardiac output and peripheral resistance, indicating that patients in the treatment period have poor heart function. No difference was found in the degree of data dispersion between the two groups. Cardiovascular side effects caused by breast cancer treatment can mainly be shown in the pulse wave time domain.

4.
Proc Natl Acad Sci U S A ; 120(33): e2209631120, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37549274

ABSTRACT

Most current climate models predict that the equatorial Pacific will evolve under greenhouse gas-induced warming to a more El Niño-like state over the next several decades, with a reduced zonal sea surface temperature gradient and weakened atmospheric Walker circulation. Yet, observations over the last 50 y show the opposite trend, toward a more La Niña-like state. Recent research provides evidence that the discrepancy cannot be dismissed as due to internal variability but rather that the models are incorrectly simulating the equatorial Pacific response to greenhouse gas warming. This implies that projections of regional tropical cyclone activity may be incorrect as well, perhaps even in the direction of change, in ways that can be understood by analogy to historical El Niño and La Niña events: North Pacific tropical cyclone projections will be too active, North Atlantic ones not active enough, for example. Other perils, including severe convective storms and droughts, will also be projected erroneously. While it can be argued that these errors are transient, such that the models' responses to greenhouse gases may be correct in equilibrium, the transient response is relevant for climate adaptation in the next several decades. Given the urgency of understanding regional patterns of climate risk in the near term, it would be desirable to develop projections that represent a broader range of possible future tropical Pacific warming scenarios-including some in which recent historical trends continue-even if such projections cannot currently be produced using existing coupled earth system models.

5.
PLoS One ; 18(5): e0285191, 2023.
Article in English | MEDLINE | ID: mdl-37134111

ABSTRACT

OBJECTIVE: Aortic stenosis (AS) is a heart valve disease characterized by left ventricular outflow fixed obstruction. It can be managed by surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). However, real-world evidence for TAVI or SAVR outcomes is lacking in Taiwan. This study aimed to compare the clinical outcomes of TAVI and SAVR for treating of AS in Taiwan. MATERIALS AND METHODS: The National Health Insurance Research Database is a nationally representative cohort that contains detailed registry and claims data from all 23 million residents of Taiwan. This retrospective cohort study used this database to compare patients who underwent SAVR (bioprosthetic valves) or TAVI from 2017 to 2019. Survival outcomes and length of hospital stay (LOS) and intensive care unit (ICU) stay between TAVI and SAVR in the matched cohort. A Cox proportional hazards model was performed to identify the effect of treatment type on survival rates while controlling variables including age, gender, and comorbidities. RESULTS: We identified 475 and 1605 patients who underwent TAVI and SAVR with a bioprosthetic valve, respectively. Patients who underwent TAVI were older (82.19 vs. 68.75 y/o) and more likely to be female (55.79% vs. 42.31%) compared with patients who underwent SAVR. Propensity score matching (PSM) on age, gender, and Elixhauser Comorbidity Index (ECI) score revealed that 375 patients who underwent TAVI were matched with patients who underwent SAVR. A significant difference was found in survival rates between TAVI and SAVR. The 1-year mortality rate was 11.44% with TAVI and 17.55% with SAVR. Both the mean total LOS (19.86 vs. 28.24 days) and mean ICU stay (6.47 vs. 11.12 days) for patients who underwent TAVI were shorter than those who underwent SAVR. CONCLUSION: Patients who had undergone TAVI had better survival outcomes and shorter LOS compared with patients who had undergone SAVR in Taiwan.


Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis Implantation , Transcatheter Aortic Valve Replacement , Humans , Female , Male , Aortic Valve/surgery , Transcatheter Aortic Valve Replacement/adverse effects , Cohort Studies , Retrospective Studies , Taiwan/epidemiology , Risk Factors , Heart Valve Prosthesis Implantation/adverse effects , Treatment Outcome
6.
Front Psychol ; 14: 994903, 2023.
Article in English | MEDLINE | ID: mdl-37228333

ABSTRACT

Most studies on word repetition have demonstrated that repeated stimuli yield reductions in brain activity. Despite the well-known repetition reduction effect, some literature reports repetition enhancements in electroencephalogram (EEG) activities. However, although studies of object and face recognition have consistently demonstrated both repetition reduction and enhancement effects, the results of repetition enhancement effects were not consistent in studies of visual word recognition. Therefore, the present study aimed to further investigate the repetition effect on the P200, an early event-related potential (ERP) component that indexes the coactivation of lexical candidates during visual word recognition. To achieve a high signal-to-noise ratio, EEG signals were decomposed into various modes by using the Hilbert-Huang transform. Results demonstrated a repetition enhancement effect on P200 activity in alpha-band oscillation and that lexicality and orthographic neighborhood size would influence the magnitude of the repetition enhancement effect on P200. These findings suggest that alpha activity during visual word recognition might reflect the coactivation of orthographically similar words in the early stages of lexical processing. Meantime, there were repetition reduction effects on ERP activities in theta-delta band oscillation, which might index that the lateral inhibition between lexical candidates would be omitted in repetition.

7.
bioRxiv ; 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36909633

ABSTRACT

The sense of smell has potent effects on appetite, but the underlying neural mechanisms are largely a mystery. The hypothalamic arcuate nucleus contains two subsets of neurons linked to appetite: AgRP (agouti-related peptide) neurons, which enhance appetite, and POMC (pro-opiomelanocortin) neurons, which suppress appetite. Here, we find that AgRP and POMC neurons receive indirect inputs from partially overlapping areas of the olfactory cortex, thus identifying their sources of odor signals. We also find neurons directly upstream of AgRP or POMC neurons in numerous other areas, identifying potential relays between the olfactory cortex and AgRP or POMC neurons. Transcriptome profiling of individual AgRP neurons reveals differential expression of receptors for multiple neuromodulators. Notably, known ligands of the receptors define subsets of neurons directly upstream of AgRP neurons in specific brain areas. Together, these findings indicate that higher olfactory areas can differentially influence AgRP and POMC appetite neurons, that subsets of AgRP neurons can be regulated by different neuromodulators, and that subsets of neurons upstream of AgRP neurons in specific brain areas use different neuromodulators, together or in distinct combinations to modulate AgRP neurons and thus appetite.

8.
Front Psychol ; 14: 1105346, 2023.
Article in English | MEDLINE | ID: mdl-36874840

ABSTRACT

Introduction: Speech comprehension involves context-based lexical predictions for efficient semantic integration. This study investigated how noise affects the predictability effect on event-related potentials (ERPs) such as the N400 and late positive component (LPC) in speech comprehension. Methods: Twenty-seven listeners were asked to comprehend sentences in clear and noisy conditions (hereinafter referred to as "clear speech" and "noisy speech," respectively) that ended with a high-or low-predictability word during electroencephalogram (EEG) recordings. Results: The study results regarding clear speech showed the predictability effect on the N400, wherein low-predictability words elicited a larger N400 amplitude than did high-predictability words in the centroparietal and frontocentral regions. Noisy speech showed a reduced and delayed predictability effect on the N400 in the centroparietal regions. Additionally, noisy speech showed a predictability effect on the LPC in the centroparietal regions. Discussion: These findings suggest that listeners achieve comprehension outcomes through different neural mechanisms according to listening conditions. Noisy speech may be comprehended with a second-pass process that possibly functions to recover the phonological form of degraded speech through phonetic reanalysis or repair, thus compensating for decreased predictive efficiency.

9.
Cardiol Ther ; 12(1): 159-169, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36522569

ABSTRACT

INTRODUCTION: Mitral regurgitation (MR) is characterized by systolic blood flow reversal from the left ventricle to the left atrium. A 2019 study indicated that in the USA, clinically significant MR (sMR) is associated with a substantial healthcare cost burden. In Taiwan, few data are available to describe the clinical characteristics, treatment patterns, and economic burden of patients with sMR. METHODS: Using the National Health Insurance Research Database (NHIRD), a national, detailed claims database of all 23 million residents of Taiwan, we conducted a retrospective cohort study to identify patients with sMR and quantify the impact of the disease on Taiwan's healthcare system. We classified patients with sMR into three cohorts based on disease etiology: functional MR (sFMR), degenerative MR (sDMR), and uncharacterized MR (sUMR). RESULTS: We compared patient characteristics across cohorts and estimated attributable healthcare utilization and costs during the 12-month follow-up period. Our research shows that in Taiwan, patients with sFMR were older, sicker, and presented at casualty (emergency department) more frequently than those with sDMR and sUMR. Meanwhile, patients with sDMR had the highest 12-month healthcare expenditures across the cohorts. CONCLUSION: These findings are inconsistent with what has been shown in the USA, which warrants further investigation.

10.
Int J Psychophysiol ; 183: 19-31, 2023 01.
Article in English | MEDLINE | ID: mdl-36375629

ABSTRACT

Prior studies involving adults have shown that words can elicit emotional processing, with emotion-label (e.g., happiness) and emotion-laden words (e.g., gift) having distinct processes. However, limited studies have explored the developmental changes in these processes in relation to emotional valence. To address this question, this exploratory study measured event-related potentials (ERPs) in 11-14-year-old children/adolescents (N = 25) and adults (N = 23) while performing an emotional categorization task. The stimuli used were two-character Chinese words, with factors for word type (emotion-label versus emotion-laden) and valence (positive versus negative). To confirm word emotionality, neutral words were also included and compared with all emotional words. The results showed that adults exhibited reduced N400 amplitudes to emotion-label words compared to emotion-laden ones in both positive and negative valence contexts. The differentiation was only sustained for negative valence in the late positive component (LPC). Similar scalp distributions of the effects of word type were found in children/adolescents; however, they exhibited a more prolonged processing of all emotional words than adults. These results suggest that the processing of emotion-label and emotion-laden words are distinct in late childhood, and this discrepancy varies with emotional valence and increasing age.


Subject(s)
Electroencephalography , Evoked Potentials , Child , Adult , Adolescent , Humans , Male , Female , Evoked Potentials/physiology , Emotions/physiology
11.
J Pharm Sci ; 112(3): 740-750, 2023 03.
Article in English | MEDLINE | ID: mdl-36170906

ABSTRACT

Liposomes have been used to improve therapeutic efficacy of drugs by increasing their bioavailability and altering biodistribution. The loading capacity of small molecules in liposomes remains a critical issue. Besides, the manufacturing process of liposomes requires multi-step procedures which hinders the clinical development. In this study, we developed a promising lipid-based nanocarriers (LN) delivery system for hydrophilic charged compounds using doxycycline (Doxy) as a model drug. This Doxy-loaded lipid nanocarrier (LN-Doxy) was fabricated by microfluidic technology. Design of experiments (DoE) was constructed to outline the interactions among the critical attributes of formulation, the parameters of microfluidic systems and excipient compositions. Response surface methodology (RSM) was furthered used for the optimization of LN-Doxy formulation. The LN-Doxy developed in this study showed high drug to lipid ratio and uniform distribution of particle size. Compared to Doxy solution, this LN-Doxy has reduced in vitro cellular toxicity and significant therapeutic efficacy which was verified in a peritonitis animal model. These results show the feasibility of using microfluidic technology combined with QbD approach to develop the LN formulation with high loading efficiency for ionizable hydrophilic drugs.


Subject(s)
Doxycycline , Liposomes , Animals , Doxycycline/therapeutic use , Microfluidics/methods , Tissue Distribution , Lipids , Particle Size
12.
Biomedicines ; 10(11)2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36359294

ABSTRACT

(Background) The coronavirus disease 2019 (COVID-19) that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries high infectivity and mortality. Efficient intervention strategies are urgently needed. Avian immunoglobulin Y (IgY) showed efficacy against viral infection whereas the in vivo efficacy remains unclear. (Methods) We immunized laying hens with S1, S1 receptor-binding domain (S1-RBD), or S2 subunits of the SARS-CoV-2 spike (S) protein. After immunization, IgYs were collected and extracted from the egg yolks. The neutralization potential of IgYs was examined by the plaque reduction neutralization test (PRNT). The bioutility of IgYs was examined in Syrian hamsters in vivo. (Results) IgYs exhibited typical banding patterns in SDS-PAGE and Western blot and were immunoreactive against S1, S1-RBD, and S2 subunits. The plaque reduction neutralization test (PRNT) showed that all purified IgYs potently neutralized different SARS-CoV-2 strains in vitro. In Syrian hamsters, the combination of IgYs for S1-RBD and S2 subunits administered before or after SARS-CoV-2 infection effectively restored body weight loss and reduced intrapulmonary lesions and the amount of immunoreactive N protein-positive cells, which were caused by SARS-CoV-2 infection. (Conclusions) Collectively, IgYs specific for S protein subunits effectively neutralized SARS-CoV-2 in vitro and in vivo and may serve as prophylactic or therapeutic antibodies in the prevention or treatment of COVID-19.

13.
Nat Commun ; 13(1): 6156, 2022 10 18.
Article in English | MEDLINE | ID: mdl-36257997

ABSTRACT

Tropical cyclones (TCs) cause devastating damage to life and property. Historical TC data is scarce, complicating adequate TC risk assessments. Synthetic TC models are specifically designed to overcome this scarcity. While these models have been evaluated on their ability to simulate TC activity, no study to date has focused on model performance and applicability in TC risk assessments. This study performs the intercomparison of four different global-scale synthetic TC datasets in the impact space, comparing impact return period curves, probability of rare events, and hazard intensity distribution over land. We find that the model choice influences the costliest events, particularly in basins with limited TC activity. Modelled direct economic damages in the North Indian Ocean, for instance, range from 40 to 246 billion USD for the 100-yr event over the four hazard sets. We furthermore provide guidelines for the suitability of the different synthetic models for various research purposes.


Subject(s)
Cyclonic Storms , Probability , Indian Ocean
14.
Neurosci Res ; 185: 49-61, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36075457

ABSTRACT

Alzheimer's disease (AD) is the leading cause of dementia which afflicts tens of millions of people worldwide. Despite many scientific progresses to dissect the AD's molecular basis from studies on various mouse models, it has been suffered from evolutionary species differences. Here, we report generation of a non-human primate (NHP), common marmoset model ubiquitously expressing Amyloid-beta precursor protein (APP) transgenes with the Swedish (KM670/671NL) and Indiana (V717F) mutations. The transgene integration of generated two transgenic marmosets (TG1&TG2) was thoroughly investigated by genomic PCR, whole-genome sequencing, and fluorescence in situ hybridization. By reprogramming, we confirmed the validity of transgene expression in induced neurons in vitro. Moreover, we discovered structural changes in specific brain regions of transgenic marmosets by magnetic resonance imaging analysis, including in the entorhinal cortex and hippocampus. In immunohistochemistry, we detected increased Aß plaque-like structures in TG1 brain at 7 years old, although evident neuronal loss or glial inflammation was not observed. Thus, this study summarizes our attempt to establish an NHP AD model. Although the transgenesis approach alone seemed not sufficient to fully recapitulate AD in NHPs, it may be beneficial for drug development and further disease modeling by combination with other genetically engineered models and disease-inducing approaches.


Subject(s)
Alzheimer Disease , Amyloid beta-Protein Precursor , Animals , Alzheimer Disease/metabolism , Amyloid beta-Peptides/genetics , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Brain/metabolism , Callithrix/genetics , Disease Models, Animal , In Situ Hybridization, Fluorescence , Mice, Transgenic , Transgenes
15.
Biomedicines ; 10(6)2022 May 27.
Article in English | MEDLINE | ID: mdl-35740280

ABSTRACT

Doxorubicin (Dox) is a widely known chemotherapeutic drug that has been encapsulated into liposomes for clinical use, such as Doxil® and Myocet®. Both of these are prepared via remote loading methods, which require multistep procedures. Additionally, their antitumor efficacy is hindered due to the poor drug release from PEGylated liposomes in the tumor microenvironment. In this study, we aimed to develop doxorubicin-loaded lipid-based nanocarriers (LNC-Dox) based on electrostatic interaction using microfluidic technology. The resulting LNC-Dox showed high loading capacity, with a drug-to-lipid ratio (D/L ratio) greater than 0.2, and high efficacy of drug release in an acidic environment. Different lipid compositions were selected based on critical packing parameters and further studied to outline their effects on the physicochemical characteristics of LNC-Dox. Design of experiments was implemented for formulation optimization. The optimized LNC-Dox showed preferred release in acidic environments and better therapeutic efficacy compared to PEGylated liposomal Dox in vivo. Thus, this study provides a feasible approach to efficiently encapsulate doxorubicin into lipid-based nanocarriers fabricated by microfluidic rapid mixing.

16.
J Chin Med Assoc ; 85(6): 709-716, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35316248

ABSTRACT

BACKGROUND: Plain abdominal radiography including supine and erect abdominal radiographs (SAR and EAR) is a frequently used image modality for preliminary evaluation of acute abdomen. We aimed to explore which one of the SAR or EAR has a higher diagnostic value in overall diagnosis of acute abdomen, including their respective advantages over each other for the various underlying diseases. METHODS: We retrospectively analyzed the imaging findings of plain abdominal radiography of patients with acute abdomen who received abdominal computed tomography (CT) within 24 hours at the emergency department of a medical center in northern Taiwan between October 2019 and February 2020. Final diagnosis was made by CT reports and clinical data. The relevance between the imaging findings and clinical diagnosis in the groups of SAR and EAR were compared. RESULTS: A total of 1009 cases with acute abdomen were included, of which 341 (33.8%) underwent EAR and 668 (66.2%) underwent SAR. Among them, 820 cases had final diagnosis confirmed by CT and clinical data. In comparison of the diagnostic relevance of SAR and EAR, there were no significant difference in the overall acute abdomen, but EAR showed a better diagnostic relevance in cases with bowel obstruction than SAR did (100% vs 87.2%, p < 0.05). No statistical difference in other abdominal diseases. CONCLUSION: There is no significant difference between SAR and EAR in evaluation of overall acute abdomen. However, EARs has a diagnostic advantage over SAR for evaluation of suspected bowel obstruction.


Subject(s)
Abdomen, Acute , Intestinal Obstruction , Abdomen, Acute/diagnostic imaging , Decision Making , Humans , Radiography, Abdominal/methods , Retrospective Studies
17.
Front Immunol ; 13: 1080897, 2022.
Article in English | MEDLINE | ID: mdl-36618412

ABSTRACT

Background: Drug repurposing is a fast and effective way to develop drugs for an emerging disease such as COVID-19. The main challenges of effective drug repurposing are the discoveries of the right therapeutic targets and the right drugs for combating the disease. Methods: Here, we present a systematic repurposing approach, combining Homopharma and hierarchal systems biology networks (HiSBiN), to predict 327 therapeutic targets and 21,233 drug-target interactions of 1,592 FDA drugs for COVID-19. Among these multi-target drugs, eight candidates (along with pimozide and valsartan) were tested and methotrexate was identified to affect 14 therapeutic targets suppressing SARS-CoV-2 entry, viral replication, and COVID-19 pathologies. Through the use of in vitro (EC50 = 0.4 µM) and in vivo models, we show that methotrexate is able to inhibit COVID-19 via multiple mechanisms. Results: Our in vitro studies illustrate that methotrexate can suppress SARS-CoV-2 entry and replication by targeting furin and DHFR of the host, respectively. Additionally, methotrexate inhibits all four SARS-CoV-2 variants of concern. In a Syrian hamster model for COVID-19, methotrexate reduced virus replication, inflammation in the infected lungs. By analysis of transcriptomic analysis of collected samples from hamster lung, we uncovered that neutrophil infiltration and the pathways of innate immune response, adaptive immune response and thrombosis are modulated in the treated animals. Conclusions: We demonstrate that this systematic repurposing approach is potentially useful to identify pharmaceutical targets, multi-target drugs and regulated pathways for a complex disease. Our findings indicate that methotrexate is established as a promising drug against SARS-CoV-2 variants and can be used to treat lung damage and inflammation in COVID-19, warranting future evaluation in clinical trials.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Cricetinae , Methotrexate/pharmacology , Methotrexate/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Inflammation/drug therapy , Computational Biology
18.
Front Neurosci ; 15: 728905, 2021.
Article in English | MEDLINE | ID: mdl-34803580

ABSTRACT

Purpose: The rearranged during transfection (RET) receptor tyrosine kinase plays a key role in transducing signals related to cell growth and differentiation. Ret mutant mice show abnormal retinal activity and abnormal levels and morphology of bipolar cells, yet die on the 21st day after birth as a result of renal underdevelopment. To extend the observation period, we generated the Ret conditional knockout Chx10-Cre;C-Ret lx/lx mouse model and analyzed the retinal function and morphological changes in mature and aging Chx10-Cre;C-Ret lx/lx mice. Methods: Retina-specific depletion of Ret was achieved using mice with floxed alleles of the Ret gene with CHX10-driven Cre recombinase; floxed mice without Cre expression were used as controls. Retinal function was examined using electroretinography (ERG), and 2-, 4-, 12-, and 24-month-old mice were analyzed by hematoxylin staining and immunohistochemistry to evaluate retinal morphological alterations. The ultrastructure of photoreceptor synapses was evaluated using electron microscopy. Results: The results of the ERG testing showed that b-wave amplitudes were reduced in Chx10-Cre;C-Ret lx/lx mice, whereas a-waves were not affected. A histopathological analysis revealed a thinner and disorganized outer plexiform layer at the ages of 12 and 24 months in Chx10-Cre;C-Ret lx/lx mice. Moreover, the data provided by immunohistochemistry showed defects in the synapses of photoreceptor cells. This result was confirmed at the ultrastructural level, thus supporting the participation of Ret in the morphological changes of the synaptic ribbon. Conclusion: Our results provide evidence of the role of Ret in maintaining the function of the retina, which was essential for preserving the structure of the synaptic ribbon and supporting the integrity of the outer plexiform layer.

19.
Int Heart J ; 62(5): 1026-1034, 2021 Sep 30.
Article in English | MEDLINE | ID: mdl-34544973

ABSTRACT

Studies conducted in developed nations have shown that increase in life expectancy has brought with it a rise in the incidence and treatment of degenerative aortic and mitral heart valve diseases. Current standards recommend valve replacement among even some asymptomatic patients. In this research, we examine the epidemiology of valvular heart disease and rate of valve replacement in Taiwan, where life expectancy now stands at 80.69 years. Patients were enrolled based on claims from a widely used national database and categorized into cohorts defined by type of valve disease and, further, by valve replacements and type of valve (mechanical, porcine, or bovine). Data, including disease type, age, and gender, were analyzed to determine annual and cumulative incidence rates and prosthetic usage from 2000 to 2017. Results showed that across the cohorts, the cumulative incidence rate in 2017 was 3.59%, and in the aortic valve cohort, the percentage of surgical valve replacement for those ≥60 years was 6.99%. Compared with other developed nations, this demonstrates that incidence rates are slightly higher, yet surgical replacements are less than half that of other developed nations. This under-treatment of patients with valvular heart disease presents an important public health challenge in Taiwan.


Subject(s)
Aortic Valve/surgery , Heart Valve Diseases/epidemiology , Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/methods , Mitral Valve/surgery , Aged , Aged, 80 and over , Aortic Valve/pathology , Bioprosthesis/statistics & numerical data , Bioprosthesis/trends , Cohort Studies , Databases, Factual , Female , Heart Valve Prosthesis/statistics & numerical data , Humans , Incidence , Life Expectancy , Male , Middle Aged , Mitral Valve/pathology , Public Health/legislation & jurisprudence , Retrospective Studies , Taiwan/epidemiology
20.
BMC Ophthalmol ; 21(1): 322, 2021 Sep 06.
Article in English | MEDLINE | ID: mdl-34488687

ABSTRACT

BACKGROUND: Full-thickness macular hole (FTMH) is a rare complication in retinitis pigmentosa (RP) patients and may increase intraoperative challenges. Furthermore, lens capsular flap transplantation and inverted internal limiting membrane (ILM) flap were reported to close complicated FTMH successfully. Here, we present a case of bilateral advanced RP complicated by a FTMH treated with a novel lens capsular flap transplantation and inverted internal limiting membrane flap. CASE PRESENTATION: A 46-year-old presented to our hospital with a complaint of progressively blurred vision and metamorphopsia in both eyes. Spectral-domain optical coherence tomography revealed a FTMH with retinoschisis in the right eye and another FTMH in the left eye. ILM peeling with inverted ILM flap technique was performed on the right eye and ILM peeling with anterior lens capsular flap technique was performed on the left eye. Post-operative follow-up showed successful closure of the FTMH and improved vision in both eyes. CONCLUSIONS: In our present case, flap-assisted techniques for retinitis pigmentosa with macular hole result in excellent visual and anatomic outcomes.


Subject(s)
Retinal Perforations , Retinitis Pigmentosa , Basement Membrane , Humans , Middle Aged , Retinal Perforations/diagnosis , Retinal Perforations/etiology , Retinal Perforations/surgery , Retinitis Pigmentosa/complications , Retrospective Studies , Tomography, Optical Coherence , Visual Acuity , Vitrectomy
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