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1.
ACS Omega ; 9(25): 27610-27617, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38947845

RESUMEN

Glycol lignin (GL) is produced via the acid-catalyzed solvolysis of softwood meal using glycols such as polyethylene glycol. The physicochemical and thermal properties of GL are expected to be controllable by varying the glycol type. In this study, caprylyl glycol (CG), which is a biobased glycol derived from the caprylic acid component of coconut and palm oils, was used to investigate the effects on the acid-catalyzed solvolysis of softwood. The reactions were performed at 140, 150, and 160 °C for 30-120 min to obtain lignin derivatives (CG-lignin: CGL). The chemical and physical properties of CGLs were investigated. Two-dimensional heteronuclear single-quantum coherence nuclear magnetic resonance analysis suggested that CGL possesses an α-CG-ß-O-4 structure as CG is grafted onto the lignin structure. CGLs prepared at higher reaction temperatures exhibited lower molecular weights. The thermomechanical analysis of CGL revealed a glass transition temperature of 89-96 °C and a viscous thermal flow temperature of 134-155 °C.

2.
Vaccines (Basel) ; 12(7)2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39066433

RESUMEN

Current mRNA vaccines against SARS-CoV-2 effectively induce systemic and cell-mediated immunity and prevent severe disease. However, they do not induce mucosal immunity that targets the primary route of respiratory infection, and their protective effects wane after a few months. Intranasal vaccines have some advantages, including their non-invasiveness and the additional ability to activate mucosal immunity. In this study, we aimed to explore the effectiveness of an intranasally inoculated spike protein of SARS-CoV-2 mixed with a carboxy-vinyl polymer (S-CVP), a viscous agent. Intranasally inoculated S-CVP strongly induced antigen-specific IgG, including neutralizing antibodies, in the mucosal epithelium and serum and cellular immunity compared to the spike protein mixed with aluminum potassium sulfate. Furthermore, IgA production was detected only with S-CVP vaccination. S-CVP-inoculation in mice significantly suppressed the viral load and inflammation in the lung and protected mice against SARS-CoV-2 challenges, including an early circulating strain and the Omicron BA.1 variant in a manner dependent on CD8+ cells and monocytes/neutrophils. Surprisingly, high antibody responses and protective effects against multiple variants of SARS-CoV-2, including Omicron BA.5, persisted for at least 15 months after the S-CVP immunization. Hence, we propose intranasal inoculation with S-CVP as a promising vaccine strategy against SARS-CoV-2.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38928921

RESUMEN

Predictive factors associated with a decline in swallowing function after 2 years were examined in 3409 Japanese older people aged ≥ 75 years who had undergone a dental checkup in Gifu Prefecture, Japan. Participants with normal swallowing function in a baseline survey in April 2018 were followed for 2 years. Swallowing function was assessed using a repetitive saliva swallowing test. In our study, 429 participants (13%) who were swallowing less than three times in 30 s based on a repetitive saliva swallowing test after 2 years were diagnosed as those with decline in swallowing function. Multivariate logistic regression analyses showed the decline in swallowing function after 2 years was associated with the male gender (odds ratio [ORs]: 0.772; 95% confidence interval [CIs]: 0.615-0.969), age ≥ 81 years (presence; ORs: 1.523; 95% CIs: 1.224-1.895), support/care-need certification (presence; ORs: 1.815; 95% CIs: 1.361-2.394), periodontal pocket depth (PPD) ≥ 4 mm (presence; ORs: 1.469; 95% CIs: 1.163-1.856), difficulty in biting hard food (yes; ORs: 1.439; 95% CIs: 1.145-1.808), choking on tea and water (yes; ORs: 2.543; 95% CIs: 2.025-3.193), and dry mouth (yes; ORs: 1.316; 95% CIs: 1.052-1.646) at baseline. Therefore, the dental checkup items associated with a decline in swallowing function after 2 years were a PPD ≥ 4 mm, difficulty in biting hard food, choking on tea and water, and dry mouth. PPD status and confirming to the self-administered questionnaire about biting, choking, and dry mouth may be useful in predicting future decline in swallowing function.


Asunto(s)
Deglución , Humanos , Anciano , Masculino , Femenino , Japón , Anciano de 80 o más Años , Deglución/fisiología , Trastornos de Deglución , Factores de Riesgo , Pueblos del Este de Asia
4.
J Anus Rectum Colon ; 8(2): 132-136, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38689780

RESUMEN

Background: Spatial and temporal heterogeneities of RAS and other molecular genes should be considered in the treatment of metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs); acquired RAS mutation is sometimes observed at disease progression of treatment with the anti-EGFR mAb. At the same time, discrepancy of RAS status from tissues and circulating tumor DNA (ctDNA) in the same patient is sometimes observed. Based on this, we commenced two observational studies to clarify these heterogeneities of RAS and BRAF in mCRC, using next generation sequencing from liquid biopsy. Methods/Design: RAS-trace study is an observational study to monitor ctDNA RAS/BRAF/PIK3CA status every 4-12 weeks using the Plasma-SeqSensei™ CRC RUO Kit (Sysmex Inostics GmbH) in mCRC with RAS/BRAF wild-type (wt) on tumor tissue. The primary endpoint was the time to the acquired RAS mutations. A total of 42 patients has been accrued. RAS-trace-2 study is also an observational study aimed at comparing the efficacy of the anti-EGFR mAb in ctDNA RAS/BRAF wt with ctDNA RAS or BRAF mutant mCRC patients, whose RAS/BRAF are wt in tumor tissue. The primary endpoint was progression-free survival in patients with ctDNA RAS/BRAF wt and RAS or BRAF mutant. A total of 240 patients will be accrued over 2 years. Discussion: These trials will help us understanding the clinical significance of spatial and temporal heterogeneities of RAS, BRAF and other genes, while optimizing the anti-EGFR mAb treatment strategies in mCRC.

5.
Microbiol Spectr ; 12(5): e0041724, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38606982

RESUMEN

Paramyxo- and filovirus genomes are equipped with bipartite promoters at their 3' ends to initiate RNA synthesis. The two elements, the primary promoter element 1 (PE1) and the secondary promoter element 2 (PE2), are separated by a spacer region that must be precisely a multiple of 6 nucleotides (nts), indicating these viruses adhere to the "rule of six." However, our knowledge of PE2 has been limited to a narrow spectrum of virus species. In this study, a comparative analysis of 1,647 paramyxoviral genomes from a public database revealed that the paramyxovirus PE2 can be clearly categorized into two distinct subcategories: one marked by C repeats at every six bases (exclusive to the subfamily Orthoparamyxovirinae) and another characterized by CG repeats every 6 nts (observed in the subfamilies Avulavirinae and Rubulavirinae). This unique pattern collectively mirrors the evolutionary lineage of these subfamilies. Furthermore, we showed that PE2 of the Rubulavirinae, with the exception of mumps virus, serves as part of the gene-coding region. This may be due to the fact that the Rubulavirinae are the only paramyxoviruses that cannot propagate without RNA editing. Filoviruses have three to eight consecutive uracil repeats every six bases (UN5) in PE2, which is located in the 3' end region of the genome. We obtained PE2 sequences from 2,195 filoviruses in a public database and analyzed the sequence conservation among virus species. Our results indicate that the continuity of UN5 hexamers is consistently maintained with a high degree of conservation across virus species. IMPORTANCE: The genomic intricacies of paramyxo- and filoviruses are highlighted by the bipartite promoters-promoter element 1 (PE1) and promoter element 2 (PE2)-at their 3' termini. The spacer region between these elements follows the "rule of six," crucial for genome replication. By a comprehensive analysis of paramyxoviral genome sequences, we identified distinct subcategories of PE2 based on C and CG repeats that were specific to Orthoparamyxovirinae and Avulavirinae/Rubulavirinae, respectively, mirroring their evolutionary lineages. Notably, the PE2 of Rubulavirinae is integrated into the gene-coding region, a unique trait potentially linked to its strict dependence on RNA editing for virus growth. This study also focused on the PE2 sequences in filovirus genomes. The strict conservation of the continuity of UN5 among virus species emphasizes its crucial role in viral genome replication.


Asunto(s)
Filoviridae , Genoma Viral , Filogenia , Regiones Promotoras Genéticas , Regiones Promotoras Genéticas/genética , Genoma Viral/genética , Filoviridae/genética , Filoviridae/clasificación , Paramyxoviridae/genética , Paramyxoviridae/clasificación , Humanos , ARN Viral/genética , Evolución Molecular , Animales
6.
Sci Rep ; 14(1): 5858, 2024 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-38467855

RESUMEN

The relationship between oral functions and dementia was examined in 7384 older adults (age ≥ 75 years) who visited a dental clinic in Gifu, Japan. Participants without dementia in a baseline survey in April 2018 were followed until March 2021. As oral functions, chewing function, tongue and lip function, and swallowing function were assessed by self-administered questionnaire, by oral diadochokinesis test, and by repetitive saliva swallowing test, respectively. The presence of systemic diseases was based on data obtained from the National Database of Health Insurance of Japan. At follow-up, 415 (6%) participants were diagnosed with dementia. Multivariate logistic regression analyses showed the presence of dementia at follow-up was associated with female (odds ratio [OR] 1.386; 95% confidence interval [CI] 1.117-1.719), age (OR 1.078; CI 1.056-1.101), regular dental checkups (absence; OR 1.452; CI 1.180-1.788), brushing frequency ≥ twice/day (absence; OR 1.510; CI 1.194-1.911), decayed teeth (presence; OR 1.328; CI 1.071-1.648), swallowing function (poor; OR 1.484; CI 1.135-1.939) at baseline. It was found that poor swallowing function was associated with the future onset of dementia.


Asunto(s)
Trastornos de Deglución , Demencia , Humanos , Femenino , Anciano , Japón/epidemiología , Deglución , Cepillado Dental , Demencia/epidemiología , Salud Bucal
7.
Front Immunol ; 14: 1209945, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37545501

RESUMEN

Intranasal vaccines that elicit mucosal immunity are deemed effective against respiratory tract infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their ability to induce humoral immunity characterized by immunoglobulin A (IgA) and IgG production is low. It has been reported that vaccination with a mixture of a viscous base carboxyvinyl polymer (CVP) and viral antigens induced robust systemic and mucosal immune responses. In this study, we analyzed the behavior of immunocompetent cells in the nasal cavity over time by spatial transcriptome profiling induced immediately after antigen vaccination using CVP. We established a method for performing spatial transcriptomics using the Visium system in the mouse nasal cavity and analyzed gene expression profiles within the nasal cavity after intranasal vaccination. Glycoprotein 2 (Gp2)-, SRY-box transcription factor 8 (Sox8)-, or Spi-B transcription factor (Spib)-expressing cells were increased in the nasal passage (NP) region at 3-6 hr after SARS-CoV-2 spike protein and CVP (S-CVP) vaccination. The results suggested that microfold (M) cells are activated within a short period of time (3-6 hr). Subsequent cluster analysis of cells in the nasal cavity showed an increase in Cluster 9 at 3-6 hr after intranasal vaccination with the S-CVP. We found that Il6 in Cluster 9 had the highest log2 fold values within the NP at 3-6 hr. A search for gene expression patterns similar to that of Il6 revealed that the log2 fold values of Edn2, Ccl20, and Hk2 also increased in the nasal cavity after 3-6 hr. The results showed that the early response of immune cells occurred immediately after intranasal vaccination. In this study, we identified changes in gene expression that contribute to the activation of M cells and immunocompetent cells after intranasal vaccination of mice with antigen-CVP using a time-series analysis of spatial transcriptomics data. The results facilitated the identification of the cell types that are activated during the initial induction of nasal mucosal immunity.


Asunto(s)
COVID-19 , Transcriptoma , Humanos , Animales , Ratones , Cavidad Nasal/química , Interleucina-6 , Anticuerpos Antivirales , SARS-CoV-2 , Vacunación/métodos , Perfilación de la Expresión Génica
8.
Int J Rheum Dis ; 26(12): 2572-2575, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37287416

RESUMEN

Gastrointestinal manifestations are a very rare complication of dermatomyositis (DM) and are much less frequent in adult cases than in juvenile cases. Only a few previous papers have reported adult patients who had DM with anti-nuclear matrix protein 2 (anti-NXP2) antibodies and who developed gastrointestinal ulcers. Herein, we report a similar case of a 50-year-old man who had DM with anti-NXP2 antibodies followed by relapsing multiple gastrointestinal ulcers. Even after the administration of prednisolone, his muscle weakness and myalgia deteriorated and gastrointestinal ulcers relapsed. In contrast, intravenous immunoglobulin and azathioprine improved his muscle weakness and gastrointestinal ulcers. Based on the parallel disease activity of the muscular and gastrointestinal symptoms, we considered that his gastrointestinal ulcers were a complication of DM with anti-NXP2 antibodies. We also propose that early intensive immunosuppressive therapy would be required for the muscular and gastrointestinal symptoms in DM with anti-NXP2 antibodies.


Asunto(s)
Dermatomiositis , Masculino , Adulto , Humanos , Persona de Mediana Edad , Dermatomiositis/complicaciones , Dermatomiositis/diagnóstico , Dermatomiositis/tratamiento farmacológico , Úlcera/diagnóstico , Úlcera/tratamiento farmacológico , Úlcera/etiología , Inmunoglobulinas Intravenosas , Inmunosupresores/uso terapéutico , Debilidad Muscular , Autoanticuerpos
9.
Open Vet J ; 13(12): 1769-1775, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38292717

RESUMEN

Background: Macrorhabdus ornithogaster, a yeast-like fungus, has the potential to infect various bird species, including companion birds. Although birds infected with M. ornithogaster may often remain asymptomatic, the infection can develop into chronic wasting gastritis and even progress to gastric cancer, highlighting the importance of early detection of M. ornithogaster infection. Despite direct fecal examination being a commonly used diagnostic method, the polymerase chain reaction (PCR) is anticipated to offer a higher detection rate. However, the actual diagnostic accuracy of the PCR for M. ornithogaster remains unknown. Case Description: Ninety fecal samples collected from companion birds that visited or were admitted to a hospital, regardless of their stage of Macrorhabdus diagnosis or treatment, were subjected to PCR testing. An accuracy analysis was then performed, considering symptomatology, direct fecal testing (FT), and sequencing. The PCR test had a sensitivity of 83.33%, specificity of 95.00%, false negative rate of 16.67%, false positive rate of 5.00%, positive predictive value of 89.29%, negative predictive value of 91.94%, prevalence of 33.33%, positive likelihood ratio of 16.67, negative likelihood ratio of 0.18, and diagnostic odds ratio of 95.00. Conclusion: The findings suggest that the PCR for Macrorhabdus possesses high diagnostic accuracy, with the ability to accurately identify uninfected individuals as negative. While the direct fecal examination is appropriate for routine primary screening, in cases where M. ornithogaster is not detected by FT, the PCR may provide a more accurate and definitive diagnosis due to its high specificity.


Asunto(s)
Enfermedades de las Aves , Aves , Micosis , Animales , Enfermedades de las Aves/microbiología , Aves/microbiología , Heces , Micosis/microbiología , Micosis/veterinaria , Reacción en Cadena de la Polimerasa/veterinaria
10.
Front Microbiol ; 13: 967019, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36466631

RESUMEN

As long as the coronavirus disease-2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with altered antigenicity will emerge. The development of vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 variants is urgently required. We have developed a vaccine consisting of the attenuated vaccinia virus Dairen-I (DIs) strain platform carrying the SARS-CoV-2 S gene (rDIs-S). rDIs-S induced neutralizing antibody and T-lymphocyte responses in cynomolgus macaques and human angiotensin-converting enzyme 2 (hACE2) transgenic mice, and the mouse model showed broad protection against SARS-CoV-2 isolates ranging from the early-pandemic strain (WK-521) to the recent Omicron BA.1 variant (TY38-873). Using a tandem mass tag (TMT)-based quantitative proteomic analysis of lung homogenates from hACE2 transgenic mice, we found that, among mice subjected to challenge infection with WK-521, vaccination with rDIs-S prevented protein expression related to the severe pathogenic effects of SARS-CoV-2 infection (tissue destruction, inflammation, coagulation, fibrosis, and angiogenesis) and restored protein expression related to immune responses (antigen presentation and cellular response to stress). Furthermore, long-term studies in mice showed that vaccination with rDIs-S maintains S protein-specific antibody titers for at least 6 months after a first vaccination. Thus, rDIs-S appears to provide broad and durable protective immunity against SARS-CoV-2, including current variants such as Omicron BA.1 and possibly future variants.

11.
Artículo en Inglés | MEDLINE | ID: mdl-36554840

RESUMEN

The aim was to examine the relationships between oral functions and support/care-need certification in older people aged ≥ 75 years using the National Health Insurance (NHI) database system and data from Kani City, Gifu, Japan. In total, 732 older Japanese people aged ≥ 75 years who did not have support/care-need certification and underwent dental check-ups in Kani City in 2017 were followed up until 2020. Chewing state, tongue and lip function, and swallowing function were assessed by a self-administered questionnaire, an oral diadochokinesis test, and a repetitive saliva-swallowing test, respectively. The presence or absence of systemic diseases and of support/care-need certification was based on data collected by the NHI database. At follow up, 121 (17%) participants had support/care-need certification. The participants with support/care-need certification included more women (p < 0.001) and older people (p < 0.001); and had more hypertension (p = 0.003), musculoskeletal disorders (p < 0.001), pneumonia (p = 0.044), poor chewing state (p < 0.001), and poor swallowing function (p = 0.003) than those without support/care-need certification. Furthermore, the presence of support/care-need certification at follow up was associated with sex (woman: odds ratio [OR], 2.120; 95% confidence interval [CI], 1.354 to 3.317), age (OR, 1.203; CI, 1.139 to 1.270), chewing state (poor: OR, 2.534; CI, 1.409 to 4.557), and swallowing function (poor: OR, 2.372; CI, 1.248 to 4.510) at baseline. However, tongue and lip function were not associated with support/care-need certification. The results indicate that older Japanese people aged ≥ 75 years with a poor chewing state and poor swallowing function at baseline had a higher risk for support/care-need certification after three years.


Asunto(s)
Trastornos de Deglución , Pueblos del Este de Asia , Humanos , Femenino , Anciano , Estudios de Cohortes , Deglución , Lengua , Japón
12.
Clin Med Insights Oncol ; 16: 11795549221137135, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36408335

RESUMEN

Background: A trial with trifluridine/tipiracil (FTD/TPI) versus placebo in patients with heavily pretreated metastatic gastric cancer showed that FTD/TPI is effective with manageable toxicity in these patients. However, real-world data on the effects of FTD/TPI in patients with advanced gastric cancer (AGC) are limited. Methods: We retrospectively collected and analyzed the clinicopathological data of patients with AGC who received FTD/TPI monotherapy at our institutions (Kobe City Medical Center General Hospital, Osaka Red Cross Hospital, Himeji Red Cross Hospital, and Kansai Medical University Hospital) between September 2019 and July 2021. Tumor responses were evaluated based on the Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival (OS) and progression-free survival were estimated using the Kaplan-Meier method. Results: A total of 53 patients were included in the study. The median age was 70 (range, 37-85) years; 39 patients (74%) were men; the numbers of patients with Eastern Cooperative Oncology Group performance status scores of 0, 1, and 2 were 10 (19%), 39 (74%), and 4 (8%), respectively; and 27 patients (51%) had diffuse-type histology. A total of 29 patients (56%) had ascites. Prior nivolumab therapy was administered to 49 patients (92%). The response rate and disease control rate (DCR) were 2% and 35%, respectively. The median progression-free survival was 2.4 months, and OS was 5.8 months. Patients with ascites exhibited significantly shorter OS (8.6 vs 4.7 months, P = .0291) than those without ascites, and DCR (54% vs 18%, P = .0055) was significantly worse in patients with ascites. There was no significant difference in the frequency of adverse events of grade 3 or higher between patients with and without ascites. Conclusion: In a real-world setting, FTD/TPI has similar effectiveness as late-line chemotherapy for patients with AGC, including those who previously had received nivolumab.

13.
J Clin Med ; 11(20)2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-36294421

RESUMEN

Nivolumab improves overall survival (OS) in patients with advanced gastric cancer (AGC) refractory to at least two previous chemotherapy regimens. We investigated whether changes in body weight and nutrition from first-line chemotherapy to nivolumab affected its efficacy. The correlation between weight change and nutritional status up to the start of nivolumab treatment and OS and progression-free survival (PFS) after starting nivolumab treatment was determined. Nutritional status was examined using the C-reactive protein/albumin ratio (CAR). A loss in body weight (LBW) from the onset of the first treatment of <4.5% led to OS prolongation and improved PFS outcomes. The median OS values in the LBW < 4.5% and ≥4.5% groups were 11.4 and 3.6 months, respectively. Similarly, changes in CAR from first-line chemotherapy (ΔCAR) affected OS; the ΔCAR < 0.01 group had a better prognosis than the ΔCAR ≥ 0.01 group. The median OS values in the ΔCAR < 0.01 and ≥0.01 groups were 9.4 and 4.5 months, respectively. The median OS in the group with LBW < 4.5% and ΔCAR < 0.01 was 12.9 months. LBW and deterioration of nutritional status following first-line chemotherapy are poor prognostic factors in AGC patients who received nivolumab as third- or later-line therapy. Early intervention to maintain body weight and nutritional status may improve the efficacy of immune checkpoint inhibitors.

14.
J Cardiol Cases ; 26(4): 286-288, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36187311

RESUMEN

A 71-year-old male with history of a right lung lobectomy for cancer of the right lung complained of resting chest pain. Through the typical echocardiographic findings, takotsubo syndrome was suspected; however, because of dextroversion of the heart, the standard 12­lead electrocardiogram did not show the typical findings of takotsubo syndrome. Based on the finding of the chest-X-ray, in order to adjust for his dextroversion of the heart, the electrodes were then placed on the right side of his chest as modified right-sided precordial leads, in which leads V1-2 were equivalent to basal portion and V5-6 to the apex of the dextroversion of his heart. Negative T waves in the apical leads (V5-6) as a typical finding of takotsubo syndrome were clearly seen. Based on coronary angiogram and left ventriculogram, takotsubo syndrome was definitively diagnosed. Learning objectives: The proper modification of the precordial leads with consideration of the heart position can provide a valuable finding and may be very useful in diagnosing patients with cardiac malposition complicated by cardiac diseases in which identification of impaired site is important.

15.
Sci Rep ; 12(1): 13560, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35945265

RESUMEN

Members of the order Bunyavirales infect a wide variety of host species, including plants, animals and humans, and pose a threat to public health. Major families in this order have tri-segmented negative-sense RNA genomes, the 5' and 3' ends of which form complementary strands that serve as a replication promoter. Elucidation of the mechanisms by which viral polymerases recognize the promoter to initiate RNA synthesis is important for understanding viral replication and pathogenesis, and developing antivirals. A list of replication promoter configuration patterns may provide details on the differences in the replication mechanisms among bunyaviruses. By using public sequence data of all known bunyavirus species, we constructed a comprehensive list of the replication promoters comprising 40 nucleotides in both the 5' and 3' ends of the genome that form a specific complementary strand. Among tri-segmented bunyaviruses, members of the family Nairoviridae, including the highly pathogenic Crimean-Congo hemorrhagic fever virus, have evolved a GC-rich promoter structure differing from that of other families. The unique promoter structure might be related to the large genome size of the family Nairoviridae among bunyaviruses, and the large genome architecture might confer pathogenic advantages. The promoter list provided in this report is useful for predicting the virus family-specific replication mechanisms of bunyaviruses.


Asunto(s)
Bunyaviridae , Virus de la Fiebre Hemorrágica de Crimea-Congo , Virus ARN , Animales , Bunyaviridae/química , Bunyaviridae/genética , Virus de la Fiebre Hemorrágica de Crimea-Congo/genética , Humanos , ARN , Virus ARN/genética , Replicación Viral/genética
16.
Sci Rep ; 12(1): 4150, 2022 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-35264719

RESUMEN

Models of animals that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can usefully evaluate the efficacy of vaccines and therapeutics. In this study, we demonstrate that infection with the SARS-CoV-2 B.1.351 variant (TY8-612 strain) induces bodyweight loss and inflammatory cytokine/chemokine production in wild-type laboratory mice (BALB/c and C57BL/6 J mice). Furthermore, compared to their counterparts, BALB/c mice had a higher viral load in their lungs and worse symptoms. Importantly, infecting aged BALB/c mice (older than 6 months) with the TY8-612 strain elicited a massive and sustained production of multiple pro-inflammatory cytokines/chemokines and led to universal mortality. These results indicated that the SARS-CoV-2 B.1.351 variant-infected mice exhibited symptoms ranging from mild to fatal depending on their strain and age. Our data provide insights into the pathogenesis of SARS-CoV-2 and may be useful in developing prophylactics and therapeutics.


Asunto(s)
COVID-19/patología , SARS-CoV-2/fisiología , Envejecimiento , Animales , COVID-19/mortalidad , COVID-19/virología , Quimiocinas/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Pulmón/patología , Pulmón/virología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Análisis de Componente Principal , ARN Viral/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Carga Viral
17.
J Virol ; 96(4): e0206721, 2022 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-34878809

RESUMEN

Paramyxovirus genomes, like that of human parainfluenza virus type 2 (hPIV2), have lengths of precisely multiples-of-six nucleotides ("rule of six"), where each nucleoprotein subunit (NP) binds exactly six nucleotides. Ten residues of its RNA binding groove contact the genome RNA; but only one, Q202, directly contacts a nucleotide base. The mutation of NPQ202 leads to two phenotypes: the ability of the viral polymerase to replicate minigenomes with defective bipartite promoters where NPwt is inactive, and the inability to rescue rPIV2 carrying this point mutation by standard means. The absence of an rPIV2 NPQ202A prevented further study of the latter phenotype. By extensive and repeated cocultivation of transfected cells, an rPIV2 carrying this mutation was finally recovered, and this virus was apparently viable due to the presence of an additional NP mutation (I35L). Our results suggest that these two phenotypes are due to separate effects of the Q202 mutation, and that the problematic rescue phenotype may be due to the inability of the transfected cell to incorporate viral nucleocapsids during virus budding. IMPORTANCE Paramyxovirus genomes are contained within a noncovalent homopolymer of its nucleoprotein (NP) and form helical nucleocapsids (NC) whose 3' ends contain the promoters for the initiation of viral RNA synthesis. This work suggests that these NC 3' ends may play another role in the virus life cycle via their specific interaction with virus-modified cell membranes needed for the incorporation of viral NCs into budding virions.


Asunto(s)
Proteínas de la Nucleocápside/genética , Virus de la Parainfluenza 2 Humana/genética , Replicación Viral/genética , Animales , Línea Celular , Nucleocápside/genética , Nucleocápside/metabolismo , Proteínas de la Nucleocápside/metabolismo , Virus de la Parainfluenza 2 Humana/crecimiento & desarrollo , Mutación Puntual , Liberación del Virus
18.
J Epidemiol ; 32(2): 105-111, 2022 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-34776499

RESUMEN

BACKGROUND: Tokyo, the capital of Japan, is a densely populated city of >13 million people, so the population is at high risk of epidemic severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. A serologic survey of anti-SARS-CoV-2 IgG would provide valuable data for assessing the city's SARS-CoV-2 infection status. Therefore, this cross-sectional study estimated the anti-SARS-CoV-2 IgG seroprevalence in Tokyo. METHODS: Leftover serum of 23,234 hospital visitors was tested for antibodies against SARS-CoV-2 using an iFlash 3000 chemiluminescence immunoassay analyzer (Shenzhen YHLO Biotech, Shenzhen, China) with an iFlash-SARS-CoV-2 IgG kit (YHLO) and iFlash-SARS-CoV-2 IgG-S1 kit (YHLO). Serum samples with a positive result (≥10 AU/mL) in either of these assays were considered seropositive for anti-SARS-CoV-2 IgG. Participants were randomly selected from patients visiting 14 Tokyo hospitals between September 1, 2020 and March 31, 2021. No participants were diagnosed with coronavirus disease 2019 (COVID-19), and none exhibited COVID-19-related symptoms at the time of blood collection. RESULTS: The overall anti-SARS-CoV-2 IgG seroprevalence among all participants was 1.83% (95% confidence interval [CI], 1.66-2.01%). The seroprevalence in March 2021, the most recent month of this study, was 2.70% (95% CI, 2.16-3.34%). After adjusting for population age, sex, and region, the estimated seroprevalence in Tokyo was 3.40%, indicating that 470,778 individuals had a history of SARS-CoV-2 infection. CONCLUSIONS: The estimated number of individuals in Tokyo with a history of SARS-CoV-2 infection was 3.9-fold higher than the number of confirmed cases. Our study enhances understanding of the SARS-CoV-2 epidemic in Tokyo.


Asunto(s)
COVID-19 , Anticuerpos Antivirales , Estudios Transversales , Hospitales , Humanos , Inmunoglobulina G , SARS-CoV-2 , Estudios Seroepidemiológicos , Tokio/epidemiología
19.
Carbohydr Polym ; 269: 118312, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34294326

RESUMEN

Highly-stretchable self-standing curdlan (1,3-ß-d-glucan) hydrogels were prepared via chemical cross-linking using various cross-linkers, including ethylene glycol diglycidyl ether, 1,4-butandiol diglycidyl ether, and 1,6-hexanediol diglycidyl ether. Tensile testing of the curdlan hydrogels revealed that the hydrogels had good elongation properties with 600%-900% elongation strain from their original length regardless of the cross-linker length. Stretched-dried-gel films were prepared by stretching of the hydrogels and subsequent drying. The tensile strength and Young's modulus of the stretched-dried-gel-films were 117-148 MPa and 1.6 GPa, respectively, and these values were markedly improved compared with the non-stretched films. X-ray measurements revealed that the stretched dried-gel films had oriented crystalline domains with an 80% of degree of orientation. These results indicate that the curdlan molecular chains were oriented and crystallized during the process of stretching and drying of the hydrogels. As a result, the stretched-dried-films showed a high tensile strength owing to strain-induced crystallization.

20.
Carbohydr Polym ; 251: 116794, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33142549

RESUMEN

We prepared self-standing chemically cross-linked hydrogels from 1,3-α-d-glucan (Mw = 2.0 × 105) and 1,3-ß-d-glucans (low-molecular-weight (LMW): Mw = 2.0 × 105, high-molecular-weight (HMW): Mw = 1.0 × 106), using ethylene glycol diglycidyl ether (EGDGE) as a cross-linker. Uniaxial compressive tests using cylindrical hydrogels of the cross-linked glucans were conducted. Both the 1,3-α-d-glucan and LMW-1,3-ß-d-glucan hydrogels were highly deformable and shape-deformable; they could be compressed without breaking to 60% and 80% strain, respectively, and recovered 80% of their original height. The Young's moduli of the 1,3-α-d-glucan and LMW-1,3-ß-d-glucan hydrogels indicated that the 1,3-α-d-glucan hydrogels were harder than the 1,3-ß-d-glucan hydrogels. The HMW-1,3-ß-d-glucan hydrogels were more deformable and had better shape recovery than the LMW-1,3-ß-d-glucans; they could be compressed by up to 90% maximum strain, and recovered almost 100% of their original height from 80% strain. Cyclic compression tests were performed to study their network structure.


Asunto(s)
Glucanos/química , beta-Glucanos/química , Secuencia de Carbohidratos , Fuerza Compresiva , Reactivos de Enlaces Cruzados , Módulo de Elasticidad , Resinas Epoxi , Hidrogeles/química , Fenómenos Mecánicos , Estructura Molecular , Peso Molecular
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