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Virus Research Oct 2023Cetacean morbillivirus (CeMV) is an enveloped, non-segmented, negative-stranded RNA virus that infects marine mammals, spreading across species and causing lethal...
Cetacean morbillivirus (CeMV) is an enveloped, non-segmented, negative-stranded RNA virus that infects marine mammals, spreading across species and causing lethal disease outbreaks worldwide. Among the eight proteins encoded by the CeMV genome, the haemagglutinin (H) glycoprotein is responsible for the virus attachment to host cell receptors. CeMV H represents an attractive target for antiviral and diagnostic research, yet the elucidation of the molecular mechanisms underlying its role in infection and inter-species transmission was hampered thus far due to the unavailability of recombinant versions of the protein. Here we present the cloning, expression and purification of a recombinant CeMV H ectodomain (rH-ecto), providing an initial characterization of its biophysical and structural properties. Sodium dodecyl sulphate - polyacrylamide gel electrophoresis (PAGE) combined to Western blot analysis and periodic acid Schiff assay showed that CeMV rH-ecto is purifiable at homogeneity from insect cells as a secreted, soluble and glycosylated protein. Miniaturized differential scanning fluorimetry, Blue Native PAGE and size exclusion chromatography coupled to multiangle light scattering revealed that CeMV rH-ecto is globularly folded, thermally stable and exists in solution in the oligomeric states of dimer and multiple of dimers. Furthermore, negative stain electron microscopy single particle analysis allowed us to delineate a low-resolution molecular architecture of the CeMV rH-ecto dimer, which recapitulates native assemblies from other morbilliviral H proteins, such as those from measles virus and canine distemper virus. This set of experiments by orthogonal techniques validates the CeMV rH-ecto as an experimental model for future biochemical studies on its structure and functions.
PubMed: 37769814
DOI: 10.1016/j.virusres.2023.199231 -
World Journal of Gastrointestinal... Mar 2024The Alcian blue (AB) and periodic acid Schiff (PAS) stains are representative mucus markers in gastric signet ring cell carcinoma (SRCC). They are low-cost special...
BACKGROUND
The Alcian blue (AB) and periodic acid Schiff (PAS) stains are representative mucus markers in gastric signet ring cell carcinoma (SRCC). They are low-cost special staining methods used to detect acidic mucus and neutral mucus, respectively. However, the clinical importance of the special combined AB and PAS stain is unclear.
AIM
To investigate AB expression, PAS expression and the AB-to-PAS (A/P) ratio in gastric SRCC patients and to assess patient prognosis.
METHODS
Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS, and signet ring cell positivity was assessed quantitatively. Immunohistochemical staining for Ki67, protein 53 (P53) and human epidermal growth factor receptor 2 (HER2) was performed simultaneously. The cancer-specific survival (CSS) rate was estimated Kaplan-Meier analysis. Cox proportional hazards models were used for univariate and multivariate survival analyses.
RESULTS
Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup ( < 0.001). The 3-year CSS rate in the A/P ≤ 0.5 group was significantly greater than that in the A/P > 0.5 group ( = 0.042). Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter, lymph node metastasis, vessel carcinoma embolus, tumor stage, the A/P ratio and the expression of Ki67, P53 and the PAS. Cox multivariate regression analysis confirmed that low PAS expression [hazard ratio (HR) = 3.809, 95% confidence interval (CI): 1.563-9.283, = 0.003] and large tumor diameter (HR = 2.761, 95%CI: 1.086-7.020, = 0.033) were independent risk factors for poor prognosis.
CONCLUSION
A/P > 0.5 is potentially a risk factor for prognosis, and low PAS expression is an independent risk factor in the prognosis of gastric SRCC. PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.
PubMed: 38577442
DOI: 10.4251/wjgo.v16.i3.687 -
International Journal of Ophthalmology 2023To investigate the effects of diquafosol sodium (DQS) for dry eye model induced with povidone-iodine (PI) solution.
AIM
To investigate the effects of diquafosol sodium (DQS) for dry eye model induced with povidone-iodine (PI) solution.
METHODS
Ten Sprague Dawley rats as the control group. Thirty Sprague Dawley rats were used to establish the dry eye model with stimulation of 10 g/L PI for 14d, then divided rats into three groups: dry eye group with no treatment (DED group, =10); phosphate buffer saline treated group (PBS group, =10); diquafosol treated group (DQS group, =10). Clinical changes were observed by tear production test, fluorescein staining, tear break-up time (TBUT) test, corneal confocal microscope and ocular surface comprehensive analyzer. Eyeballs were collected on day 10 of treatment for hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and alcian blue staining. TUNEL assay, polymorphonuclear (PMN) and mucin 1 (MUC1) immunofluorescence were performed and corneal ultrastructural changes were detected by electron microscopy.
RESULTS
Compared with DED and PBS groups, tear production (7.26±0.440 4.07±0.474 mm; 7.26±0.440 3.74±0.280 mm; all <0.01) and TBUT (7.37±0.383s 1.49±0.260s; 7.37±0.383s 1.42±0.437s; all <0.01) were significantly increased in DQS group. HE, PAS, and alcian blue staining and MUC1 immunofluorescence showed mucins and conjunctival goblet cells density (8.45±0.718 5.21±0.813 cells/0.1 mm; 8.45±0.718 5.36±0.615 cells/0.1 mm; all <0.01) increased in DQS group. Confocal microscopy, PMN immunofluorescence and TUNEL staining showed inflammatory infiltration and corneal epithelial cells apoptosis decreased in DQS group. The increased number of microvilli in corneal epithelial and the recovered cell junction were observed in DQS group.
CONCLUSION
PI instillation can induce goblet cells and mucin loss, epithelial cell apoptosis and inflammation, which are consistent with the pathological manifestations of dry eye. Diquafosol can repair the ocular surface damage caused by PI, reduce corneal inflammation, inhibit corneal epithelial cell apoptosis, promote mucin secretion and maintain tear film stability.
PubMed: 38111924
DOI: 10.18240/ijo.2023.12.02 -
Advanced Science (Weinheim,... Aug 2023DNA has been used as a robust material for the building of a variety of nanoscale structures and devices owing to its unique properties. Structural DNA nanotechnology... (Review)
Review
DNA has been used as a robust material for the building of a variety of nanoscale structures and devices owing to its unique properties. Structural DNA nanotechnology has reported a wide range of applications including computing, photonics, synthetic biology, biosensing, bioimaging, and therapeutic delivery, among others. Nevertheless, the foundational goal of structural DNA nanotechnology is exploiting DNA molecules to build three-dimensional crystals as periodic molecular scaffolds to precisely align, obtain, or collect desired guest molecules. Over the past 30 years, a series of 3D DNA crystals have been rationally designed and developed. This review aims to showcase various 3D DNA crystals, their design, optimization, applications, and the crystallization conditions utilized. Additionally, the history of nucleic acid crystallography and potential future directions for 3D DNA crystals in the era of nanotechnology are discussed.
Topics: Nucleic Acid Conformation; DNA; Nanotechnology
PubMed: 37327311
DOI: 10.1002/advs.202302021 -
Nature Communications Jul 2023Enzymes fold into unique three-dimensional structures to distribute their reactive amino acid residues, but environmental changes can disrupt their essential folding and...
Enzymes fold into unique three-dimensional structures to distribute their reactive amino acid residues, but environmental changes can disrupt their essential folding and lead to irreversible activity loss. The de novo synthesis of enzyme-like active sites is challenging due to the difficulty of replicating the spatial arrangement of functional groups. Here, we present a supramolecular mimetic enzyme formed by self-assembling nucleotides with fluorenylmethyloxycarbonyl (Fmoc)-modified amino acids and copper. This catalyst exhibits catalytic functions akin those of copper cluster-dependent oxidases, and catalytic performance surpasses to date-reported artificial complexes. Our experimental and theoretical results reveal the crucial role of periodic arrangement of amino acid components, enabled by fluorenyl stacking, in forming oxidase-mimetic copper clusters. Nucleotides provide coordination atoms that enhance copper activity by facilitating the formation of a copper-peroxide intermediate. The catalyst shows thermophilic behavior, remaining active up to 95 °C in an aqueous environment. These findings may aid the design of advanced biomimetic catalysts and offer insights into primordial redox enzymes.
Topics: Copper; Biomimetics; Oxidoreductases; Metalloproteins; Amino Acids; Nucleotides
PubMed: 37419896
DOI: 10.1038/s41467-023-39779-6 -
International Journal of Molecular... Dec 2023Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid‑β (Aβ) in the brain. The gut/brain axis may serve a role in AD...
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid‑β (Aβ) in the brain. The gut/brain axis may serve a role in AD pathogenesis. The present study investigated deposition of Aβ in the intestinal epithelium and its potential effects on intestinal barrier function in a transgenic mouse model of AD. To investigate alterations in the structure and functionality of the intestinal mucosal barrier in AD model mice, hematoxylin and eosin staining for Paneth cell count, Alcian blue‑periodic acid Schiff staining for goblet cells, immunohistochemistry and immunofluorescence for mucin (MUC)2 and wheat germ agglutin expression, transmission electron microscopy for mucosal ultrastructure, FITC‑labeled dextran assay for intestinal permeability, quantitative PCR for goblet cell precursor expression and western blot analysis for tight junction proteins, MUC2 and inflammatory cytokine detection were performed. The results showed that AD model mice exhibited excessive Aβ deposition in the intestinal epithelium, which was accompanied by increased intestinal permeability, inflammatory changes and decreased expression of tight junction proteins. These alterations in the intestinal barrier led to an increased proliferation of goblet and Paneth cells and increased mucus synthesis. Dysfunction of gut barrier occurs in AD and may contribute to its etiology. Future therapeutic strategies to reverse AD pathology may involve early manipulation of gut physiology and its microbiota.
Topics: Mice; Animals; Mucins; Alzheimer Disease; Tight Junctions; Intestinal Mucosa; Mice, Transgenic; Permeability; Tight Junction Proteins
PubMed: 37830152
DOI: 10.3892/ijmm.2023.5316 -
Journal of Pharmacy & Bioallied Sciences Jul 2023Gingival recession is defined as the apical migration of gingival margin to the cementoenamel junction. Recently, amnion membrane, the third-generation membrane which is...
Comparison of Amnion Membrane and Hyaluronic Acid in Gingival Recession Coverage and Gain in Clinical Attachment Level following Coronally Advanced Flap Procedure-A Clinical Study.
BACKGROUND
Gingival recession is defined as the apical migration of gingival margin to the cementoenamel junction. Recently, amnion membrane, the third-generation membrane which is a placental-derived tissue, has been introduced.
MATERIALS AND METHODS
Study included 45 subjects with age group of 20-60 years of both genders. Patients with Miller's Class I and Class II gingival recession were selected for the study. The progress was assessed at baseline one, three, and six months observation interval through clinical parameters RD, RW, PD, and CAL at the end of six months.
RESULTS
Recession depths in the first, third, and sixth month were 1.82 ± 0.442, 1.31 ± 0.47 mm, and 0.91 ± 0.29, respectively, which showed a significant reduction from the baseline. Recession widths in the first, second, and third weeks were 3.04 ± 0.442 mm, 1.31 ± 0.47 mm, and 1.49 ± 0.59 mm, respectively. There was a statistically significant reduction ( > 0.005) when compared to the baseline. Pocket depths in the first, third, and sixth month were 0.93 ± 0.447, 0.42 ± 0.50, and 0.24 ± 0.43 ( > 0.005) which is significant when compared to baseline. Clinical attachment levels in the first, third, and sixth month were 2.73 ± 0.751, 1.78 ± 0.70, and 1.18 ± 0.53 ( > 0.005) which is significant compared to six months.
CONCLUSION
Within the limitations of the present study, the data obtained by periodic assessment of the clinical parameters indicate the use of amnion membrane and hyaluronic acid, and proper technique may thus be the panacea for root coverage procedure.
PubMed: 37694043
DOI: 10.4103/jpbs.jpbs_202_23 -
Korean Journal of Family Medicine Feb 2024This study aimed to identify barriers and facilitators of iron and folic acid supplementation and deworming programs among school-going adolescents.
BACKGROUND
This study aimed to identify barriers and facilitators of iron and folic acid supplementation and deworming programs among school-going adolescents.
METHODS
A mixed-method observational study was conducted among adolescents in the 8th to 10th standards and their teachers across four schools in Deoghar, Jharkhand, India, using simple random sampling. The study included a questionnaire on socio-demographics, knowledge (34 items) (α=0.894), attitudes (2 items) (α=0.711) toward iron deficiency anemia, awareness of the Weekly Iron and Folic Acid Supplementation (WIFS) program and deworming (20 items) (α=0.783), and practices related to iron folic acid supplementation (IFS) and deworming, along with qualitative components. Data were analyzed using jamovi.
RESULTS
Compliance rates for IFS and deworming were 27.5% and 67.9%, respectively. The multivariable logistic regression analysis showed that sex, religion, caste, father's educational status, per capita monthly family income (PCMI), diet type, adequate knowledge, and positive attitude toward anemia influenced IFS compliance. Religion, PCMI, and prior information on the importance of deworming facilitate compliance. Implementation barriers included irregular medication supply and a lack of student awareness.
CONCLUSION
Periodic evaluation, regular sensitization, and a consistent drug supply are necessary to effectively implement WIFS and deworming programs in the study area.
PubMed: 38414372
DOI: 10.4082/kjfm.23.0100 -
Environment International Jul 2023Bioelectric field is a stimulated force to degrade xenobiotic pollutants in soils. However, the effect of bioelectric field on microplastics (MPs) aging is unclear. The...
Bioelectric field is a stimulated force to degrade xenobiotic pollutants in soils. However, the effect of bioelectric field on microplastics (MPs) aging is unclear. The degradation behavior of polyvinyl chloride (PVC), polyethylene (PE) and polylactic acid (PLA) was investigated in an agricultural soil microbial electrochemical system in which bioelectric field was generated in-situ by native microbes. Based on the density function theory, the energy gaps between the highest and the lowest occupied molecular orbitals of the three polymers with periodic structure were 4.20, 7.24 and 10.09 eV respectively, and further decreased under the electric field, indicating the higher hydrolysis potential of PLA. Meanwhile, the mass loss of PLA in the closed-circuit group (CC) was the highest on day 120, reaching 8.94%, which was 3.01-3.54 times of that without bioelectric field stimulation. This was mainly due to the enrichment of plastic-degrading bacteria and a robust co-occurrence network as the deterministic assembly process, e.g., the abundance of potential plastic-degrading bacteria on the surface of PLA and PVC in the CC increased by 1.92 and 1.30 times, respectively, compared to the open-circuit group. In terms of functional genes, the xenobiotic biodegradation and metabolism capacity of plasticsphere in the CC were stronger than that in soil, and determined by the bioaccessibility of soil nitrogen and carbon. Overall, this study explored the promoting effect of bioelectric field on the degradation of MPs and reveled the mechanism from quantum chemical calculations and microbial community analysis, which provides a novel perception to the in-situ degradation of MPs.
Topics: Microplastics; Plastics; Soil; Xenobiotics; Soil Microbiology; Polyesters
PubMed: 37329759
DOI: 10.1016/j.envint.2023.108035 -
Diabetes Research and Clinical Practice Feb 2024Robust evidence exists regarding initiation, intensification or modification of treatments. Recommendations to de-escalate therapy are lacking, specifically in diabetes.... (Review)
Review
INTRODUCTION
Robust evidence exists regarding initiation, intensification or modification of treatments. Recommendations to de-escalate therapy are lacking, specifically in diabetes. A successful treatment de-intensification reduces overtreatment, polypharmacy, and risk of adverse effects.
OBJECTIVE
To encompass current recommendations for deprescribing common drugs and create a consensus among health professionals.
METHODS
We reviewed four databases for deprescribing approaches published between 2010 and 2022. Articles were divided into different groups of drugs (for uric-acid, hypoglycemic, lipid-lowering, and psychotropic drugs).
RESULTS
Hypoglycemic agents: strategies were limited to newer agents and insulin regimens for elderly individuals. Reducing insulin was associated with 1.1% reduction of A1c over time. SGLT2i and GLP-1RAs dose reduction depends on adverse events. Lipid-lowering agents: studies show that patients with very low cholesterol have fewer cardiovascular events without associated increased risk. Antihypertensive agents: Younger patients, lower systolic blood pressure, and few comorbidities are ideal characteristics for discontinuation. Uric acid therapy: we found no recommendation for dose de-escalation. Poor treatment adherence is associated with episodes of gout and deforming arthritis in the long term.
CONCLUSION
Deprescribing hypoglycemic, statins, antihypertensives, and urate-lowering agents may be feasible in selected patients, but periodic surveillance is important. More evidence is necessary to support this decision entirely.
Topics: Humans; Aged; Goals; Hypoglycemic Agents; Diabetes Mellitus; Antihypertensive Agents; Insulin; Lipids
PubMed: 38244782
DOI: 10.1016/j.diabres.2024.111096