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Frontiers in Medicine 2024Previous studies have reported Caspase-1 () is upregulated in mouse models of Juvenile X-linked Retinoschisis (XLRS), however no functional role for in disease...
PURPOSE
Previous studies have reported Caspase-1 () is upregulated in mouse models of Juvenile X-linked Retinoschisis (XLRS), however no functional role for in disease progression has been identified. We performed electroretinogram (ERG) and standardized optical coherence tomography (OCT) in mice deficient in the Retinoschisin-1 () and and Caspase-11 genes (-KO ) to test the hypothesis that may play a role in disease evolution and or severity of disease. Currently, no studies have ventured to investigate the longer-term effects of on phenotypic severity and disease progression over time in XLRS, and specifically the effect on electroretinogram.
METHODS
-KO; mice were generated by breeding -KO mice with mice. OCT imaging was analyzed at 2-, 4-, and 15-16 months of age. Outer nuclear layer (ONL) thickness and adapted standardized cyst severity score were measured and averaged from 4 locations 500 μm from the optic nerve. Adapted standardized cyst severity score was 1: absent cysts, 2: <30 μm, 3: 30-49 μm, 4: 50-69 μm, 5: 70-99 μm, 6: >99 μm. Electroretinograms (ERG) were recorded in dark-adapted and light-adapted conditions at 2 and 4 months. Results obtained from -KO and -KO; eyes were compared with age matched WT control eyes at 2 months.
RESULTS
Intraretinal schisis was not observed on OCT in WT eyes, while schisis was apparent in most -KO and -KO; eyes at 2 and 4 months of age. There was no difference in the cyst severity score from 2 to 4 months of age, or ONL thickness from 2 to 16 months of age between -KO and -KO; eyes. ERG amplitudes were similarly reduced in -KO and -KO; compared to WT controls at 2 months of age, and there was no difference between KO and -KO; eyes at 2 or 4 months of age, suggesting no impact on the electrical function of photoreceptors over time in the absence of .
CONCLUSION
Although has been reported to be significantly upregulated in KO mice, our preliminary data suggest that removing does not modulate photoreceptor electrical function or alter the trajectory of the retinal architecture over time.
PubMed: 38938378
DOI: 10.3389/fmed.2024.1347599 -
Frontiers in Human Neuroscience 2024Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating...
INTRODUCTION
Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating differential diagnosis, particularly in disorders featuring tremors. The presence of bradykinetic features in the subset of dystonic tremors (DT), either "pure" dystonic tremors or tremors associated with dystonia, remains currently unexplored. The aim of the current study was to evaluate upper limb bradykinesia in DT patients, comparing them with healthy controls (HC) and patients with PD by observing repetitive finger tapping (FT).
METHODS
The protocol consisted of two main parts. Initially, the kinematic recording of repetitive FT was performed using optical hand tracking system (Leap Motion Controller). The values of amplitude, amplitude decrement, frequency, frequency decrement, speed, acceleration and number of halts of FT were calculated. Subsequently, three independent movement disorder specialists from different movement disorders centres, blinded to the diagnosis, rated the presence of FT bradykinesia based on video recordings.
RESULTS
Thirty-six subjects participated in the study (12 DT, 12 HC and 12 early-stage PD). Kinematic analysis revealed no significant difference in the selected parameters of FT bradykinesia between DT patients and HC. In comparisons between DT and PD patients, PD patients exhibited bigger amplitude decrement and slower FT performance. In the blinded clinical assessment, bradykinesia was rated, on average, as being present in 41.6% of DT patients, 27.7% of HC, and 91.7% of PD patients. While overall inter-rater agreement was moderate, weak agreement was noted within the DT group.
DISCUSSION
Clinical ratings indicated signs of bradykinesia in almost half of DT patients. The objective kinematic analysis confirmed comparable parameters between DT and HC individuals, with more pronounced abnormalities in PD across various kinematic parameters. Interpretation of bradykinesia signs in tremor patients with DT should be approached cautiously and objective motion analysis might complement the diagnostic process and serve as a decision support system in the choice of clinical entities.
PubMed: 38938290
DOI: 10.3389/fnhum.2024.1395827 -
Animal Bioscience Jun 2024The improvement of carcass traits is essential for the Hanwoo industry because of the Hanwoo grade determination system, and Genome-Wide Association Study (GWAS)...
OBJECTIVE
The improvement of carcass traits is essential for the Hanwoo industry because of the Hanwoo grade determination system, and Genome-Wide Association Study (GWAS) analysis is an instrumental tool for identifying the genetic factors that impact these traits. While GWAS analysis utilizing family data offers advantages in minimizing genetic bias, research on family-based GWAS in Hanwoo is currently lacking.
METHODS
This study classified Group A using both parental and offspring genetic information, and Group B based solely on offspring genetic information, to compare GWAS analysis results of Hanwoo carcass traits.
RESULTS
16 significant SNP markers (carcass weight (CWT) 7, back fat thickness (BFT) 3, marbling score (MS) 6) were identified in Group A, and 7 significant SNP markers (CWT 3, eye muscle area (EMA) 1, BFT 1, MS 2) were identified in Group B. Functional annotation analysis revealed only one common function related to carcass traits between the groups, while Protein-protein interaction (PPI) analysis indicated more gene interactions in Group A. The reliability of estimated values for common SNP markers identified between the groups was higher in Group A.
CONCLUSION
GWAS analysis utilizing parental genetic information holds greater potential for application, owing to its higher reliability of estimated values and the ability to explore numerous candidate genes.
PubMed: 38938028
DOI: 10.5713/ab.24.0303 -
Genes and Environment : the Official... Jun 2024Long non-coding RNA (lncRNA) is a group of RNA transcripts that contribute to tumor development by post-transcriptionally regulating cancer-related genes. Nasopharyngeal...
BACKGROUND
Long non-coding RNA (lncRNA) is a group of RNA transcripts that contribute to tumor development by post-transcriptionally regulating cancer-related genes. Nasopharyngeal carcinoma (NPC) is an epithelial tumor that occurs in the nasopharynx and is common in North Africa and Southeast Asia. The study investigated the functions of lncRNA TMPO-AS1 in NPC cell proliferation and apoptosis as well as its related competing endogenous RNA (ceRNA) mechanism.
METHODS
Candidate microRNA and genes that may regulated by TMPO-AS1 were predicted with the bioinformatic tool starBase. TMPO-AS1 expression in NPC tissue, cells, nuclear part, and cytoplasmic part was measured by RT-qPCR. MTT assay, EdU assay, and flow cytometry analysis were carried out to evaluate NPC cell viability, proliferation, and apoptosis, respectively. RNA immunoprecipitation assay and luciferase reporter assay were conducted to detect the binding between TMPO-AS1 and let-7c-5p or that between let-7c-5p and BCAT1.
RESULTS
TMPO-AS1 and BCAT1 showed high expression in NPC tissue and cells, while let-7c-5p was downregulated in NPC. The silencing of TMPO-AS1 suppressed NPC cell proliferation while promoting cell apoptosis. Moreover, TMPO-AS1 interacted with let-7c-5p and negatively regulated let-7c-5p expression. BCAT1 was a target of let-7c-5p and was inversely regulated by let-7c-5p in NPC cells. The repressive impact of TMPO-AS1 knockdown on NPC cell growth was countervailed by overexpressed BCAT1.
CONCLUSION
TMPO-AS1 accelerates NPC cell proliferation and represses cell apoptosis by interacting with let-7c-5p to regulate BCAT1 expression.
PubMed: 38937856
DOI: 10.1186/s41021-024-00308-6 -
Journal of Biomedical Science Jun 2024The endoplasmic reticulum (ER) employs stringent quality control mechanisms to ensure the integrity of protein folding, allowing only properly folded, processed and... (Review)
Review
The endoplasmic reticulum (ER) employs stringent quality control mechanisms to ensure the integrity of protein folding, allowing only properly folded, processed and assembled proteins to exit the ER and reach their functional destinations. Mutant proteins unable to attain their correct tertiary conformation or form complexes with their partners are retained in the ER and subsequently degraded through ER-associated protein degradation (ERAD) and associated mechanisms. ER retention contributes to a spectrum of monogenic diseases with diverse modes of inheritance and molecular mechanisms. In autosomal dominant diseases, when mutant proteins get retained in the ER, they can interact with their wild-type counterparts. This interaction may lead to the formation of mixed dimers or aberrant complexes, disrupting their normal trafficking and function in a dominant-negative manner. The combination of ER retention and dominant-negative effects has been frequently documented to cause a significant loss of functional proteins, thereby exacerbating disease severity. This review aims to examine existing literature and provide insights into the impact of dominant-negative effects exerted by mutant proteins retained in the ER in a range of autosomal dominant diseases including skeletal and connective tissue disorders, vascular disorders, neurological disorders, eye disorders and serpinopathies. Most crucially, we aim to emphasize the importance of this area of research, offering substantial potential for understanding the factors influencing phenotypic variability associated with genetic variants. Furthermore, we highlight current and prospective therapeutic approaches targeted at ameliorating the effects of mutations exhibiting dominant-negative effects. These approaches encompass experimental studies exploring treatments and their translation into clinical practice.
Topics: Humans; Endoplasmic Reticulum; Genes, Dominant; Endoplasmic Reticulum-Associated Degradation; Protein Folding; Mutation
PubMed: 38937821
DOI: 10.1186/s12929-024-01054-1 -
Thrombosis Journal Jun 2024In recent years, extracorporeal membrane oxygenation (ECMO) has been increasingly used in critically ill patients with respiratory or cardiac failure. Heparin is usually...
BACKGROUND
In recent years, extracorporeal membrane oxygenation (ECMO) has been increasingly used in critically ill patients with respiratory or cardiac failure. Heparin is usually used as anticoagulation therapy during ECMO support. However, heparin-induced thrombocytopenia (HIT) in ECMO-supported patients, which results in considerable morbidity and mortality, has not yet been well described. This meta-analysis and systematic review aimed to thoroughly report the incidence of HIT on ECMO, as well as the characteristics and outcomes of HIT patients.
METHODS
We searched the PubMed, Embase, Cochrane Library, and Scopus databases for studies investigating HIT in adult patients supported by ECMO. All studies conforming to the inclusion criteria were screened from 1975 to August 2023. Nineteen studies from a total of 1,625 abstracts were selected. The primary outcomes were the incidence of HIT and suspected HIT.
RESULTS
The pooled incidence of HIT in ECMO-supported patients was 4.2% (95% CI: 2.7-5.6; 18 studies). A total of 15.9% (95% CI: 9.0-22.8; 12 studies) of patients on ECMO were suspected of having HIT. Enzyme-linked immunosorbent assay (ELISA) is the most commonly used immunoassay. The median optical density (OD) of the ELISA in HIT-confirmed patients ranged from 1.08 to 2.10. In most studies, the serotonin release assay (SRA) was performed as a HIT-confirming test. According to the subgroup analysis, the pooled incidence of HIT in ECMO patients was 2.7% in studies whose diagnostic mode was functional assays, which is significantly lower than the incidence in studies in which the patients were diagnosed by immunoassay (14.5%). Argatroban was most commonly used as an alternative anticoagulation agent after the withdrawal of heparin. Among confirmed HIT patients, 45.5% (95% CI: 28.8-62.6) experienced thrombotic events, while 50.1% (95% CI: 24.9-75.4) experienced bleeding events. Overall, 46.6% (95% CI: 30.4-63.1) of patients on ECMO with HIT died.
CONCLUSION
According to our study, the pooled incidence of HIT in ECMO-supported patients is 4.2%, and it contributes to adverse outcomes. Inappropriate diagnostic methods can easily lead to misdiagnosis of HIT. Further research and development of diagnostic algorithms and laboratory assays are warranted.
PubMed: 38937784
DOI: 10.1186/s12959-024-00624-5 -
Cell & Bioscience Jun 2024Microvascular destabilization is the primary cause of the inner blood-retinal barrier (iBRB) breakdown and increased vascular leakage in diabetic retinopathy (DR).... (Review)
Review
Microvascular destabilization is the primary cause of the inner blood-retinal barrier (iBRB) breakdown and increased vascular leakage in diabetic retinopathy (DR). Microvascular destabilization results from the combinational effects of increased levels of growth factors and cytokines, involvement of inflammation, and the changed cell-to-cell interactions, especially the loss of endothelial cells and pericytes, due to hyperglycemia and hypoxia. As the manifestation of microvascular destabilization, the fluid transports via paracellular and transcellular routes increase due to the disruption of endothelial intercellular junctional complexes and/or the altered caveolar transcellular transport across the retinal vascular endothelium. With diabetes progression, the functional and the structural changes of the iBRB components, including the cellular and noncellular components, further facilitate and aggravate microvascular destabilization, resulting in macular edema, the neuroretinal damage and the dysfunction of retinal inner neurovascular unit (iNVU). Although there have been considerable recent advances towards a better understanding of the complex cellular and molecular network underlying the microvascular destabilization, some still remain to be fully elucidated. Recent data indicate that targeting the intricate signaling pathways may allow to against the microvascular destabilization. Therefore, efforts have been made to better clarify the cellular and molecular mechanisms that are involved in the microvascular destabilization in DR. In this review, we discuss: (1) the brief introduction of DR and microvascular destabilization; (2) the cellular and molecular components of iBRB and iNVU, and the breakdown of iBRB; (3) the matrix and cell-to-cell contacts to maintain microvascular stabilization, including the endothelial glycocalyx, basement membrane, and various cell-cell interactions; (4) the molecular mechanisms mediated cell-cell contacts and vascular cell death; (5) the altered cytokines and signaling pathways as well as the intricate network of the cytokines involved in microvascular destabilization. This comprehensive review aimed to provide the insights for microvascular destabilization by targeting the key molecules or specific iBRB cells, thus restoring the function and structure of iBRB and iNVU, to treat DR.
PubMed: 38937783
DOI: 10.1186/s13578-024-01269-7 -
Scientific Reports Jun 2024Cerium vanadate/modified bentonite (CeVO/mbt) nanocomposite with different composition percentages was synthesized through a simple one-step hydrothermal method at 180...
Cerium vanadate/modified bentonite (CeVO/mbt) nanocomposite with different composition percentages was synthesized through a simple one-step hydrothermal method at 180 ℃, and then its photocatalytic activity was evaluated by decolorizing methylene blue (MB) in an aqueous solution under light exposure. In order to increase the surface area as an important parameter in photocatalytic processes, bentonite was modified by ball mill method. The structural and optical properties of the synthesized composites were determined by XRD, FT-IR, DRS, FESEM, EDS, and BET measurements. XRD and EDS results confirmed the successful synthesis of pure CeVO. FESEM images and EDS mapping showed a proper distribution of rice-like CeVO nanoparticles on bentonite. The removal efficiency of MB with only 0.1 g of CeVO/mbt nanocomposite in 15 min was about 99%, which is significant compared to neat bentonite and pure CeVO with efficiency of 30% and 57%. The mentioned nanocomposite followed the first-order kinetics, had a reaction rate constant equal to 0.1483 min, and showed acceptable stability in five consecutive cycles.
PubMed: 38937600
DOI: 10.1038/s41598-024-65793-9 -
Scientific Reports Jun 2024We demonstrate in a proof-of-concept experiment spectral-domain optical coherence tomography where steering of the optical beam that probes the sample in a transverse...
We demonstrate in a proof-of-concept experiment spectral-domain optical coherence tomography where steering of the optical beam that probes the sample in a transverse scan does not make use of any mechanical element. Steering is done with the help of a phase-only spatial light modulator, that introduces a spatially-dependent phase between the two orthogonal polarization components of an optical beam, and some optical elements that control the polarization of light. We demonstrate that making use of the non-mechanical beam steering system considered here, we can reproduce the main traits of imaging with standard OCT that makes use of mechanical-assisted optical beam steering.
PubMed: 38937546
DOI: 10.1038/s41598-024-65125-x -
Nature Communications Jun 2024Optical spatiotemporal vortices with transverse photon orbital angular momentum (OAM) have recently become a focal point of research. In this work we theoretically and...
Optical spatiotemporal vortices with transverse photon orbital angular momentum (OAM) have recently become a focal point of research. In this work we theoretically and experimentally investigate optical spatiotemporal vortices with radial and azimuthal quantum numbers, known as spatiotemporal Laguerre-Gaussian (STLG) wavepackets. These 3D wavepackets exhibit phase singularities and cylinder-shaped edge dislocations, resulting in a multi-ring topology in its spatiotemporal profile. Unlike conventional ST optical vortices, STLG wavepackets with non-zero and values carry a composite transverse OAM consisting of two directionally opposite components. We further demonstrate mode conversion between an STLG wavepacket and an ST Hermite-Gaussian (STHG) wavepacket through the application of strong spatiotemporal astigmatism. The converted STHG wavepacket is de-coupled in intensity in space-time domain that can be utilized to implement the efficient and accurate recognition of ultrafast STLG wavepackets carried various and This study may offer new insights into high-dimensional quantum information, photonic topology, and nonlinear optics, while promising potential applications in other wave phenomena such as acoustics and electron waves.
PubMed: 38937504
DOI: 10.1038/s41467-024-49819-4