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1.
bioRxiv ; 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39372768

ABSTRACT

The continuous emergence of new SARS-CoV-2 variants requires that COVID vaccines be updated to match circulating strains. We generated B/HPIV3-vectored vaccines expressing 6P-stabilized S protein of the ancestral, B.1.617.2/Delta, or B.1.1.529/Omicron variants as pediatric vaccines for intranasal immunization against HPIV3 and SARS-CoV-2 and characterized these in hamsters. Following intranasal immunization, these B/HPIV3 vectors replicated in the upper and lower respiratory tract and induced mucosal and serum anti-S IgA and IgG. B/HPIV3 expressing ancestral or B.1.617.2/Delta-derived S-6P induced serum antibodies that effectively neutralized SARS-CoV-2 of the ancestral and B.1.617.2/Delta lineages, while the cross-neutralizing potency of B.1.1.529/Omicron S-induced antibodies was lower. Despite the lower cross-neutralizing titers induced by B/HPIV3 expressing S-6P from B.1.1.529/Omicron, a single intranasal dose of all three versions of B/HPIV3 vectors was protective against matched or heterologous WA1/2020, B.1.617.2/Delta or BA.1 (B.1.1.529.1)/Omicron challenge; hamsters were protected from challenge virus replication in the lungs, while low levels of challenge virus were detectable in the upper respiratory tract of a small number of animals. Immunization also protected against lung inflammatory response after challenge, with mild inflammatory cytokine induction associated with the slightly lower level of cross-protection of WA1/2020 and B.1.617.2/Delta variants against the BA.1/Omicron variant. Serum antibodies elicited by all vaccine candidates were broadly reactive against 20 antigenic variants, but the antigenic breadth of antibodies elicited by B/HPIV3-expressed S-6P from the ancestral or B.1.617.2/Delta variant exceeded that of the S-6P B.1.1.529/Omicron expressing vector. These results will guide development of intranasal B/HPIV3 vectors with S antigens matching circulating SARS-CoV-2 variants.

2.
Article in English | MEDLINE | ID: mdl-39384347

ABSTRACT

Background: This study addresses the gap in knowledge regarding the long-term mortality implications of postoperative acute kidney injury (PO-AKI) utilizing advanced machine learning techniques to predict outcomes more accurately than traditional statistical models. Methods: A retrospective cohort study was conducted using data from seven institutions between March 2009 and December 2019. Machine learning models were developed to predict all-cause mortality of PO-AKI patients using 23 preoperative variables and one postoperative variable. Model performance was compared to a traditional statistical approach with Cox regression analysis. The concordance index was used as a predictive performance metric to compare prediction capabilities among different models. Results: Among 199,403 patients, 2,105 developed PO-AKI. During a median follow-up of 144 months (interquartile range, 99.61-170.71 months), 472 in-hospital deaths occurred. Subjects with PO-AKI had a significantly lower survival rate than those without PO-AKI (p < 0.001). For predicting mortality, the XGBoost with an accelerated failure time model had the highest concordance index (0.7521), followed by random survival forest (0.7371), multivariable Cox regression model (0.7318), survival support vector machine (0.7304), and gradient boosting (0.7277). Conclusion: XGBoost with an accelerated failure time model was developed in this study to predict long-term mortality associated with PO-AKI. Its performance was superior to conventional models. The application of machine learning techniques may offer a promising approach to predict mortality following PO-AKI more accurately, providing a basis for developing targeted interventions and clinical guidelines to improve patient outcomes.

3.
Brain Res ; : 149272, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39395645

ABSTRACT

OBJECTIVE: Adolescents with depression is characterized by high rates of recurrence and functional impairment, with a significant association with suicide risk. Antidepressants are commonly prescribed to treat depression, yet few reproducible neurobiological markers for depression and antidepressant treatment response have been identified. Therefore, discovering a stable and reliable neurobiological marker holds significant value for both the clinical diagnosis and treatment of depression in adolescents. METHODS: One hundred and seven patients with major depressive disorder (MDD group, 30 males, 77 females, mean age: 14.80 years), and 25 healthy subjects (HC group, 13 males, 12 females, mean age: 15.72 years) were recruited to perform a two-choice oddball task related to negative emotional cues. All participants completed a self-administered questionnaire to gather demographic information. A trained psychiatrist administered the Hamilton Depression Scale (HAMD-17) to assess depression severity. Of the 107 adolescents with depression, 61 received antidepressant medication for 8 weeks, and 61 of these patients were followed up. Multichannel EEG was recorded continuously from 64 scalp electrodes using the Curry 8 system. EEG signal preprocessing and analysis was performed offline using the EEGLAB toolbox in MATLAB. The ERP component characteristics associated with emotional processing were extracted from the difference waves and statistically analyzed. RESULTS: Adolescents with depression exhibited significantly larger P300 amplitudes than healthy controls in response to both neutral and negative emotional cues. Following sertraline treatment, both depression scores and P300 amplitudes decreased significantly in adolescents with depression. Moreover, a strong positive correlation was observed between changes in depression scores and changes in P300 amplitude in response to negative emotional cues before and after treatment. CONCLUSIONS: Changes in neural reactivity to negative emotional stimuli among adolescents with depression can be selectively modulated by sertraline and are significantly associated with improvements in depressive symptoms. SIGNIFICANCE: Changes in P300 amplitude to negative emotional stimuli significantly correlate with treatment responsiveness to sertraline in adolescents with depression.

4.
J Perianesth Nurs ; 2024 09 18.
Article in English | MEDLINE | ID: mdl-39297820

ABSTRACT

PURPOSE: To explore the analgesic characteristics of ultrasound-guided great auricular nerve (GAN) block to further improve pain management. DESIGN: Single-center, prospective, randomized, controlled, and double-blind preliminary clinical trial. METHODS: Thirty-seven patients who underwent middle ear surgery were included in this study: 15 in the GAN block group (the large ear nerve block [NB] group) and 22 in the traditional anesthesia group (control [CON] group). After induction of anesthesia, the NB group was given an ultrasound-guided GAN block (0.25 % Ropivacaine 2 mL), while the CON group was exempt from the GAN block. The patient's basic information, perioperative information, the region, and numeric rating scale of postoperative pain (at 1 hour, 6 hours, 12 hours, and 24 hours), and adverse reactions were recorded. Repeated measurement analysis, t test, and Fisher exact probability method were used for statistical analysis. FINDINGS: Compared with the CON group, the numeric rating scale in the NB group was lower after surgery (1 hour: 1.18 ± 0.35 vs 0.27 ± 0.20, P = .023; 6 hours: 1.82 ± 0.37 vs 1.13 ± 0.39, P = .203; 12 hours: 1.05 ± 0.19 vs 0.20 ± 0.10, P < .001; 24 hours: 0.55 ± 0.17 vs 0.13 ± 0.09, P = .029). In the NB group, the region of pain was merely concentrated in the ear canal. In the CON group, the pain extended to areas outside the ear canal, such as tragus and mastoid (at 12 hours, P = .006). There was no significant difference in the risk of postoperative adverse reactions between the two groups. CONCLUSIONS: Ultrasound-guided GAN block can relieve patients' pain after middle ear surgery, especially in the area outside the ear canal.

5.
Biomed Pharmacother ; 179: 117338, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39278187

ABSTRACT

A recent study has introduced a recombinant fusion protein, consisting of the extracellular domain (ECD) of p75 and the Fc fragment of human immunoglobulin IgG1 (p75ECD-Fc), as a multifaceted agent within the nervous system. This research aimed to assess the effects of p75ECD-Fc on neuronal growth and the restoration of neurological functions in rats afflicted with neonatal hypoxic-ischemic encephalopathy (NHIE). In vitro analyses revealed that 1 µM p75ECD-Fc treatment markedly increased cell viability and facilitated neurite outgrowth in neurons exposed to oxygen-glucose deprivation (OGD). Subsequent in vivo studies determined that a dose of 78.6 µg/3 µl of p75ECD-Fc significantly mitigated brain damage and both acute and long-term neurological impairments, outperforming the therapeutic efficacy of hypothermia, as evidenced through behavioral assessments. Additionally, in vivo immunostaining showed that p75ECD-Fc administration enhanced neuronal survival and regeneration, and reduced astrocytosis and microglia activation in the cortex and hippocampus of NHIE rats. A noteworthy shift from A1 to A2 astrocyte phenotypes and from M1 to M2 microglia phenotypes was observed after p75ECD-Fc treatment. Furthermore, a co-expression of the p75 neurotrophin receptor (p75NTR) and Nestin was identified, with an overexpression of Nestin alleviating the neurological dysfunction induced by NHIE. Mechanistically, the neuroprotective effects of p75ECD-Fc, particularly its inhibition of neuronal apoptosis post-OGD, may be attributed to Nestin. Taken together, these results highlight the neuroprotective and anti-inflammatory effects of p75ECD-Fc treatment through the modulation of glial cell phenotypes and the Nestin-mediated inhibition of neuronal apoptosis, positioning it as a viable therapeutic approach for NHIE.


Subject(s)
Animals, Newborn , Apoptosis , Hypoxia-Ischemia, Brain , Immunoglobulin Fc Fragments , Nestin , Rats, Sprague-Dawley , Animals , Hypoxia-Ischemia, Brain/drug therapy , Hypoxia-Ischemia, Brain/pathology , Hypoxia-Ischemia, Brain/metabolism , Apoptosis/drug effects , Nestin/metabolism , Immunoglobulin Fc Fragments/pharmacology , Rats , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Neuroprotective Agents/pharmacology , Recombinant Fusion Proteins/pharmacology , Male , Cell Survival/drug effects , Microglia/drug effects , Microglia/pathology , Microglia/metabolism , Humans , Receptors, Nerve Growth Factor/metabolism , Disease Models, Animal
6.
Int J Biol Macromol ; 280(Pt 2): 135856, 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39313049

ABSTRACT

Triphala-based carbon dots (T-CDs) were successfully prepared using a simple one-step hydrothermal method. T-CDs were characterized by absorbance, fluorescence, Fourier-transform infrared, X-ray photoelectron spectroscopy, and high-resolution transmission electron microscopy. T-CDs showed bright blue fluorescence at 434 nm upon excitation at 360 nm. Functional composite films were prepared using poly(vinyl alcohol) and gelatin mixture by incorporating T-CDs and applied as a packaging film to extend the shelf life of chicken. The antibacterial activity of T-CDs against Listeria monocytogenes and Staphylococcus aureus was evaluated using well diffusion and colony count methods. T-CDs were evenly dispersed throughout the PVA/Gel solution to form a dense and uninterrupted film. They also formed strong bonds with polymer chains, which improved the tensile strength of the film from 32.44 to 42.70 MPa. Furthermore, the presence of T-CDs significantly enhanced the UV-blocking ability of the PVA/Gel films, achieving 99.7 % for UV-B and 97.2 % for UV-A. In addition, the PVA/Gel/T-CDs composite films showed excellent antioxidant, antimicrobial and UV-barrier properties, extending the shelf life of chicken. Therefore, the PVA/Gel/T-CDs composite films showed great potential as an active food packaging material to extend the shelf life and preserve the visual quality of packaged meat.

7.
Sci Rep ; 14(1): 19996, 2024 08 28.
Article in English | MEDLINE | ID: mdl-39198694

ABSTRACT

Titrating tacrolimus concentration in liver transplantation recipients remains a challenge in the early post-transplant period. This multicenter retrospective cohort study aimed to develop and validate a machine-learning algorithm to predict tacrolimus concentration. Data from 443 patients undergoing liver transplantation between 2017 and 2020 at an academic hospital in South Korea were collected to train machine-learning models. Long short-term memory (LSTM) and gradient-boosted regression tree (GBRT) models were developed using time-series doses and concentrations of tacrolimus with covariates of age, sex, weight, height, liver enzymes, total bilirubin, international normalized ratio, albumin, serum creatinine, and hematocrit. We conducted performance comparisons with linear regression and populational pharmacokinetic models, followed by external validation using the eICU Collaborative Research Database collected in the United States between 2014 and 2015. In the external validation, the LSTM outperformed the GBRT, linear regression, and populational pharmacokinetic models with median performance error (8.8%, 25.3%, 13.9%, and - 11.4%, respectively; P < 0.001) and median absolute performance error (22.3%, 33.1%, 26.8%, and 23.4%, respectively; P < 0.001). Dosing based on the LSTM model's suggestions achieved therapeutic concentrations more frequently on the chi-square test (P < 0.001). Patients who received doses outside the suggested range were associated with longer ICU stays by an average of 2.5 days (P = 0.042). In conclusion, machine learning models showed excellent performance in predicting tacrolimus concentration in liver transplantation recipients and can be useful for concentration titration in these patients.


Subject(s)
Immunosuppressive Agents , Liver Transplantation , Machine Learning , Tacrolimus , Humans , Tacrolimus/pharmacokinetics , Tacrolimus/administration & dosage , Tacrolimus/blood , Male , Female , Retrospective Studies , Middle Aged , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/administration & dosage , Adult , Republic of Korea , Aged
8.
J Neurosci ; 44(36)2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39117456

ABSTRACT

Monocular deprivation (MD) causes an initial decrease in synaptic responses to the deprived eye in juvenile mouse primary visual cortex (V1) through Hebbian long-term depression (LTD). This is followed by a homeostatic increase, which has been attributed either to synaptic scaling or to a slide threshold for Hebbian long-term potentiation (LTP) rather than scaling. We therefore asked in mice of all sexes whether the homeostatic increase during MD requires GluN2B-containing NMDA receptor activity, which is required to slide the plasticity threshold but not for synaptic scaling. Selective GluN2B blockade from 2-6 d after monocular lid suture prevented the homeostatic increase in miniature excitatory postsynaptic current (mEPSC) amplitude in monocular V1 of acute slices and prevented the increase in visually evoked responses in binocular V1 in vivo. The decrease in mEPSC amplitude and visually evoked responses during the first 2 d of MD also required GluN2B activity. Together, these results support the idea that GluN2B-containing NMDA receptors first play a role in LTD immediately following eye closure and then promote homeostasis during prolonged MD by sliding the plasticity threshold in favor of LTP.


Subject(s)
Dominance, Ocular , Excitatory Postsynaptic Potentials , Mice, Inbred C57BL , Neuronal Plasticity , Receptors, N-Methyl-D-Aspartate , Animals , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/metabolism , Mice , Male , Dominance, Ocular/physiology , Female , Neuronal Plasticity/physiology , Neuronal Plasticity/drug effects , Excitatory Postsynaptic Potentials/physiology , Excitatory Postsynaptic Potentials/drug effects , Evoked Potentials, Visual/physiology , Visual Cortex/physiology , Visual Cortex/drug effects , Excitatory Amino Acid Antagonists/pharmacology , Sensory Deprivation/physiology , Long-Term Potentiation/physiology , Long-Term Potentiation/drug effects , Long-Term Synaptic Depression/physiology , Long-Term Synaptic Depression/drug effects , Photic Stimulation/methods
9.
Cell Death Dis ; 15(8): 589, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39138148

ABSTRACT

It is still challenging to predict the efficacy of cisplatin-based therapy, particularly in relation to the activation of macroautophagy/autophagy in oral squamous cell carcinoma (OSCC). We studied the effect of selected chromatin remodeling genes on the cisplatin resistance and their interplay with autophagy in 3-dimensional tumor model and xenografts. We analyzed gene expression patterns in the cisplatin-sensitive UMSCC1, and a paired cisplatin-resistant UM-Cis cells. Many histone protein gene clusters involved in nucleosome assembly showed significant difference of expression. Gain- and loss-of-function analyses revealed an inverse correlation between cisplatin resistance and HIST1H3D expression, while a positive correlation was observed with HIST3H2A or HIST3H2B expression. In UM-Cis, HIST3H2A- and HIST3H2B-mediated chromatin remodeling upregulates autophagy status, which results in cisplatin resistance. Additionally, knockdown of HIST3H2A or HIST3H2B downregulated autophagy-activating genes via chromatin compaction of their promoter regions. MiTF, one of the key autophagy regulators upregulated in UM-Cis, negatively regulated transcription of HIST1H3D, suggesting an interplay between chromatin remodeling-dependent cisplatin resistance and autophagy. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, protein expression pattern of the selected histone protein genes were matched with the in vitro data. By examining the relationship between autophagy and chromatin remodeling genes, we identified a set of candidate genes with potential use as markers predicting chemoresistance in OSCC biopsy samples.


Subject(s)
Autophagy , Carcinoma, Squamous Cell , Chromatin Assembly and Disassembly , Cisplatin , Drug Resistance, Neoplasm , Mouth Neoplasms , Cisplatin/pharmacology , Cisplatin/therapeutic use , Humans , Autophagy/drug effects , Autophagy/genetics , Drug Resistance, Neoplasm/genetics , Chromatin Assembly and Disassembly/drug effects , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/drug therapy , Animals , Cell Line, Tumor , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/drug therapy , Gene Expression Regulation, Neoplastic/drug effects , Mice , Histones/metabolism , Mice, Nude , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Xenograft Model Antitumor Assays
10.
J Microbiol Biotechnol ; 34(8): 1592-1598, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39081248

ABSTRACT

Genotype V (GV) Japanese encephalitis virus (JEV) has been predominantly reported in the Republic of Korea (ROK) since 2010. GV JEV exhibits higher virulence and distinct antigenicity compared to other genotypes, which results in reduced efficacy of existing vaccines. Research on GV JEV is essential to minimize its clinical impact, but the only available clinical strain in the ROK is K15P38, isolated from the cerebrospinal fluid of a patient in 2015. We obtained this virus from National Culture Collection for Pathogens (NCCP) and isolated a variant forming small plaques during our research. We identified that this variant has one amino acid substitution each in the PrM and NS5 proteins compared to the reported K15P38. Additionally, we confirmed that this virus exhibits delayed propagation in vitro and an attenuated phenotype in mice. The isolation of this variant is a critical reference for researchers intending to study K15P38 obtained from NCCP, and the mutations in the small plaque-forming virus are expected to be useful for studying the pathology of GV JEV.


Subject(s)
Encephalitis Virus, Japanese , Encephalitis, Japanese , Genotype , Encephalitis Virus, Japanese/genetics , Encephalitis Virus, Japanese/isolation & purification , Encephalitis Virus, Japanese/classification , Encephalitis, Japanese/virology , Animals , Humans , Mice , Republic of Korea , Virulence , Viral Plaque Assay , Amino Acid Substitution , Female , Mutation , Cell Line , Mice, Inbred BALB C , Virus Replication
11.
Arthritis Res Ther ; 26(1): 137, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030584

ABSTRACT

OBJECTIVES: To determine the risk factors for mortality in Korean patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) in comparison to patients with RA but without ILD (RA-nonILD). METHODS: Data were extracted from a single-centre prospective cohort of RA patients with a chest computed tomography scan at an academic referral hospital in Korea. Patients with RA-ILD enroled between May 2017 and August 2022 were selected, and those without ILD were selected as comparators. The mortality rate was calculated, and the causes of each death were investigated. We used Cox proportional hazard regression with Firth's penalised likelihood method to identify the risk factors for mortality in patients with RA-ILD. RESULTS: A total of 615 RA patients were included: 200 with ILD and 415 without ILD. In the RA-ILD group, there were 15 deaths over 540.1 person-years (PYs), resulting in mortality rate of 2.78/100 PYs. No deaths were reported in the RA-nonILD group during the 1669.9 PYs. The primary causes of death were infection (nine cases) and lung cancer (five cases), with only one death attributed to ILD aggravation. High RA activity (adjusted HR 1.87, CI 1.16-3.10), baseline diffusing capacity for carbon monoxide (DLCO) < 60% (adjusted HR 4.88, 95% CI 1.11-45.94), and usual interstitial pneumonia (UIP) pattern (adjusted HR 5.13, 95% CI 1.00-57.36) were identified as risk factors for mortality in RA-ILD patients. CONCLUSION: Patients with RA-ILD have an elevated risk of mortality compared with those without ILD. Infection-related deaths are the main causes of mortality in this population. High RA activity, low DLCO, and the UIP pattern are significantly associated with the mortality in patients with RA-ILD.


Subject(s)
Arthritis, Rheumatoid , Lung Diseases, Interstitial , Humans , Lung Diseases, Interstitial/mortality , Arthritis, Rheumatoid/mortality , Arthritis, Rheumatoid/complications , Male , Female , Middle Aged , Risk Factors , Prospective Studies , Aged , Republic of Korea/epidemiology , Cohort Studies , Adult
12.
Ibrain ; 10(2): 164-171, 2024.
Article in English | MEDLINE | ID: mdl-38915949

ABSTRACT

This study aimed to provide a recommendable protocol for the preparation of brain cryosections of rats to reduce and avoid ice crystals. We have designed five different dewatering solutions (Scheme 1: dehydrate with 15%, 20%, and 30% sucrose-phosphate-buffered saline solution; Scheme 2: 20% sucrose and 30% sucrose; Scheme 3: 30% sucrose; Scheme 4: 10%, 20%, and 30% sucrose; and Scheme 5: the tissue was dehydrated with 15% and 30% sucrose polyacetate I until it sank to the bottom, followed by placement in 30% sucrose polyacetate II) to minimize the formation of ice crystals. Cryosections from different protocols were stained with Nissl staining and compared with each other by density between cells and the distance of intertissue spaces. The time required for the dehydration process from Scheme 1 to Scheme 5 was 24, 23, 24, 24, and 33 h, respectively. Density between cells gradually decreased from Scheme 1 to Scheme 5, and the distance of intertissue spaces was differentiated and irregular in different schemes according to the images of Nissl staining. We recommend the dewatering method of Scheme 4 (the brain tissues were dehydrated in 10%, 20% and 30% sucrose solution in turn until the tissue samples were completely immersed in the solution and then immersed in the next concentration solution for dehydration).

13.
Proc Natl Acad Sci U S A ; 121(25): e2316376121, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38861603

ABSTRACT

Human parainfluenza virus type 3 (HPIV3) is a major pediatric respiratory pathogen lacking available vaccines or antiviral drugs. We generated live-attenuated HPIV3 vaccine candidates by codon-pair deoptimization (CPD). HPIV3 open reading frames (ORFs) encoding the nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin-neuraminidase (HN), and polymerase (L) were modified singly or in combination to generate 12 viruses designated Min-N, Min-P, Min-M, Min-FHN, Min-L, Min-NP, Min-NPM, Min-NPL, Min-PM, Min-PFHN, Min-MFHN, and Min-PMFHN. CPD of N or L severely reduced growth in vitro and was not further evaluated. CPD of P or M was associated with increased and decreased interferon (IFN) response in vitro, respectively, but had little effect on virus replication. In Vero cells, CPD of F and HN delayed virus replication, but final titers were comparable to wild-type (wt) HPIV3. In human lung epithelial A549 cells, CPD F and HN induced a stronger IFN response, viral titers were reduced 100-fold, and the expression of F and HN proteins was significantly reduced without affecting N or P or the relative packaging of proteins into virions. Following intranasal infection in hamsters, replication in the nasal turbinates and lungs tended to be the most reduced for viruses bearing CPD F and HN, with maximum reductions of approximately 10-fold. Despite decreased in vivo replication (and lower expression of CPD F and HN in vitro), all viruses induced titers of serum HPIV3-neutralizing antibodies similar to wt and provided complete protection against HPIV3 challenge. In summary, CPD of HPIV3 yielded promising vaccine candidates suitable for further development.


Subject(s)
Codon , Parainfluenza Virus 3, Human , Vaccines, Attenuated , Virus Replication , Animals , Parainfluenza Virus 3, Human/immunology , Parainfluenza Virus 3, Human/genetics , Humans , Vaccines, Attenuated/immunology , Vaccines, Attenuated/genetics , Codon/genetics , Cricetinae , Respirovirus Infections/immunology , Respirovirus Infections/prevention & control , Respirovirus Infections/virology , Chlorocebus aethiops , Vero Cells , Open Reading Frames/genetics , Mesocricetus , Antibodies, Viral/immunology , Antibodies, Viral/blood , Viral Vaccines/immunology , Viral Vaccines/genetics , Viral Proteins/immunology , Viral Proteins/genetics , Parainfluenza Vaccines/immunology , Parainfluenza Vaccines/genetics
14.
Emerg Microbes Infect ; 13(1): 2362392, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38808613

ABSTRACT

Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV) infection, continues to pose significant public health challenges worldwide despite efficient vaccines. The virus is classified into five genotypes, among which genotype V (GV) was not detected for a long period after its initial isolation in 1952, until reports emerged from China and the Republic of Korea (ROK) since 2009. The characteristics of the virus are crucial in estimating its potential epidemiological impact. However, characterization of GV JEVs has so far been limited to two strains: Muar, the original isolate, and XZ0934, isolated in China. Two additional ROK GV JEV isolates, NCCP 43279 and NCCP 43413, are currently available, but their characteristics have not been explored. Our phylogenetic analysis revealed that GV virus sequences from the ROK segregate into two clades. NCCP 43279 and NCCP 43413 belong to different clades and exhibit distinct in vitro phenotypes. NCCP 43279 forms larger plaques but demonstrates inefficient propagation in cell culture compared to NCCP 43413. In vivo, NCCP 43279 induces higher morbidity and mortality in mice than NCCP 43413. Notably, NCCP 43279 shows more severe blood-brain barrier damage, suggesting superior brain invasion capabilities. Consistent with its higher virulence, NCCP 43279 displays more pronounced histopathological and immunopathological outcomes. In conclusion, our study confirms that the two ROK isolates are not only classified into different clades but also exhibit distinct in vitro and in vivo characteristics.


Subject(s)
Encephalitis Virus, Japanese , Encephalitis, Japanese , Genotype , Phylogeny , Encephalitis Virus, Japanese/genetics , Encephalitis Virus, Japanese/isolation & purification , Encephalitis Virus, Japanese/classification , Animals , Republic of Korea/epidemiology , Encephalitis, Japanese/virology , Encephalitis, Japanese/veterinary , Encephalitis, Japanese/epidemiology , Mice , Humans , Virulence , Cell Line , Female
15.
PLoS Pathog ; 20(5): e1012198, 2024 May.
Article in English | MEDLINE | ID: mdl-38739647

ABSTRACT

Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory illness worldwide, but there is no approved pediatric vaccine. Here, we describe the development of the live-attenuated RSV vaccine candidate Min AL as well as engineered derivatives. Min AL was attenuated by codon-pair deoptimization (CPD) of seven of the 11 RSV open reading frames (ORFs) (NS1, NS2, N, P, M, SH and L; 2,073 silent nucleotide substitutions in total). Min AL replicated efficiently in vitro at the permissive temperature of 32°C but was highly temperature sensitive (shut-off temperature of 36°C). When serially passaged at increasing temperatures, Min AL retained greater temperature sensitivity compared to previous candidates with fewer CPD ORFs. However, whole-genome deep-sequencing of passaged Min AL revealed mutations throughout its genome, most commonly missense mutations in the polymerase cofactor P and anti-termination transcription factor M2-1 (the latter was not CPD). Reintroduction of selected mutations into Min AL partially rescued its replication in vitro at temperatures up to 40°C, confirming their compensatory effect. These mutations restored the accumulation of positive-sense RNAs to wild-type (wt) RSV levels, suggesting increased activity by the viral transcriptase, whereas viral protein expression, RNA replication, and virus production were only partly rescued. In hamsters, Min AL and derivatives remained highly restricted in replication in the upper and lower airways, but induced serum IgG and IgA responses to the prefusion form of F (pre F) that were comparable to those induced by wt RSV, as well as robust mucosal and systemic IgG and IgA responses against RSV G. Min AL and derivatives were fully protective against challenge virus replication. The derivatives had increased genetic stability compared to Min AL. Thus, Min AL and derivatives with selected mutations are stable, attenuated, yet highly-immunogenic RSV vaccine candidates that are available for further evaluation.


Subject(s)
Open Reading Frames , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Vaccines , Vaccines, Attenuated , Virus Replication , Animals , Respiratory Syncytial Virus Vaccines/immunology , Respiratory Syncytial Virus Vaccines/genetics , Vaccines, Attenuated/immunology , Vaccines, Attenuated/genetics , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/virology , Cricetinae , Administration, Intranasal , Codon , Immunity, Mucosal , Antibodies, Viral/immunology , Antibodies, Viral/blood , Humans , Respiratory Syncytial Virus, Human/immunology , Respiratory Syncytial Virus, Human/genetics , Mesocricetus , Respiratory Syncytial Viruses/immunology , Respiratory Syncytial Viruses/genetics
16.
Int J Biol Macromol ; 270(Pt 1): 132343, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38750841

ABSTRACT

Color indicator films incorporating aronia extract powder (AEP) and biopolymers like agar, carrageenan, and cellulose nanofiber (CNF) were developed to monitor kimchi freshness. AEP-containing films showed strong UV-barrier properties, and reduced light transmittance by 99.12 % for agar, 98.86 % for carrageenan, and 98.67 % for CNF-based films. All AEP-films exhibited high sensitivity to pH changes and vapor exposure to ammonia and acetic acid. Color change notably influenced by the polymer type, particularly evident with ammonia vapor exposure, especially in the AEP/carrageenan film. The chemical structure and thermal stability of the biopolymers remained unchanged after AEP-addition. Tensile strength increased by 24.2 % for AEP/CNF but decreased by 19.4 % for AEP/agar and 24.3 % for AEP/carrageenan films. AEP-containing films displayed strong antioxidant activity, with 99 % free radical scavenging in ABTS and ~ 80 % in DPPH assays. Alkalized AEP-indicator films were more effective in detecting color changes during kimchi packaging tests. Among the labels, alkalized AEP/agar film showed the most obvious color change from green-gray (fresh kimchi, pH 5.5, acidity 0.48 %) to pale brown (optimal fermentation, pH 4.6, acidity 0.70 %), and pale violet-brown (over-fermented, pH 3.80, acidity 1.35 %). Alkalized AEP-indicator films offer promising real-time detection of packed fermented foods like kimchi.


Subject(s)
Agar , Carrageenan , Cellulose , Colorimetry , Food Packaging , Nanofibers , Plant Extracts , Carrageenan/chemistry , Nanofibers/chemistry , Agar/chemistry , Cellulose/chemistry , Colorimetry/methods , Food Packaging/methods , Plant Extracts/chemistry , Antioxidants/chemistry , Antioxidants/analysis , Tensile Strength , Color , Hydrogen-Ion Concentration
17.
Gastroenterology ; 167(2): 418-419, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38582269
18.
Ann Hepatobiliary Pancreat Surg ; 28(3): 337-343, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-38566519

ABSTRACT

Backgrounds/Aims: Challenges arise when translating pure laparoscopic donor right hepatectomy (PLDRH) results from Asian to Western donors, due to differences in body mass index (BMI). This study compares the outcomes of PLDRH and conventional open donor right hepatectomy (CDRH) in donors with BMI over 30. Methods: Medical records of live liver donors (BMI > 30) undergoing right hepatectomy (2010-2021) were compared: 25 PLDRH cases vs. 19 CDRH cases. Donor and recipient demographics, operative details, and outcomes were analyzed. Results: PLDRH and CDRH had similar donor and recipient characteristics. PLDRH had longer liver removal and warm ischemic times, but a shorter post-liver removal duration than CDRH. Donor complication rates were comparable, with the highest complication being grade IIIa in PLDRH, necessitating needle aspiration for biloma on postoperative day 11. Fortunately, this donor fully recovered without additional treatment. No complications exceeding Clavien-Dindo grade IIIa occurred in either group. Recipient outcomes between the groups were similar. Conclusions: This study supports PLDRH as a viable option for donors with BMI over 30, challenging the notion that high BMI should deter considering PLDRH. The findings provide valuable insights into the safety and feasibility of PLDRH, encouraging further exploration of this technique in diverse donor populations.

20.
Int J Biol Macromol ; 267(Pt 2): 131606, 2024 May.
Article in English | MEDLINE | ID: mdl-38631566

ABSTRACT

This study aimed to investigate the effect of cinnamon essential oil (CEO)-loaded metal-organic frameworks (CEO@MOF) on the properties of gelatin/pullulan (Gel/Pull)-based composite films (Gel/Pull-based films). The incorporation of CEO@MOF into Gel/Pull-based films demonstrated significant antimicrobial activity against S. aureus, S. enterica, E. coli, and L. monocytogenes. Additionally, CEO@MOF integrated film exhibited a 98.16 % ABTS radical scavenging, with no significant change in the mechanical properties of the neat Gel/Pull film. The UV blocking efficiency of the composite films increased significantly from 81.38 to 99.56 % at 280 nm with the addition of 3 wt% CEO@MOF. Additionally, Gel/Pull/CEO@MOF films effectively extended the shelf life of meat preserved at 4 °C by reducing moisture loss by 3.35 %, maintaining the pH within the threshold limit (6.2), and inhibiting bacterial growth by 99.9 %. These results propose that CEO@MOF has significant potential as an effective additive in active packaging to improve shelf life and food safety.


Subject(s)
Cinnamomum zeylanicum , Food Packaging , Gelatin , Glucans , Metal-Organic Frameworks , Oils, Volatile , Gelatin/chemistry , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Cinnamomum zeylanicum/chemistry , Food Packaging/methods , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Glucans/chemistry , Glucans/pharmacology , Food Preservation/methods , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Meat/microbiology , Animals , Microbial Sensitivity Tests
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