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Retinal ganglion cell (RGC) death and axonal loss cause irreversible vision loss upon optic nerve (ON) injury. We have independently demonstrated that mesenchymal stem cells (MSCs) and green tea extract (GTE) promote RGC survival and axonal regeneration in rats with ON injury. Here we aimed to evaluate the combined treatment effect of human bone marrow-derived MSCs (hBM-MSCs) and GTE on RGC survival and axonal regeneration after ON injury. Combined treatment of hBM-MSCs and GTE promoted RGC survival and neurite outgrowth/axonal regeneration in ex vivo retinal explant culture and in rats after ON injury. GTE increased Stat3 activation in the retina after combined treatment, and enhanced brain-derived neurotrophic factor secretion from hBM-MSCs. Treatment of 10 µg/mL GTE would not induce hBM-MSC apoptosis, but inhibited their proliferation, migration, and adipogenic and osteogenic differentiation in vitro with reducing matrix metalloproteinase secretions. In summary, this study revealed that GTE can enhance RGC protective effect of hBM-MSCs, suggesting that stem cell priming could be a prospective strategy enhancing the properties of stem cells for ON injury treatment.
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Células-Tronco Mesenquimais , Traumatismos do Nervo Óptico , Ratos , Humanos , Animais , Traumatismos do Nervo Óptico/terapia , Traumatismos do Nervo Óptico/metabolismo , Células Ganglionares da Retina/metabolismo , Osteogênese , Chá/metabolismo , Regeneração Nervosa/fisiologia , Sobrevivência Celular/fisiologia , Axônios/metabolismoRESUMO
PURPOSE: To investigate the performance of 10 MHz ultrasonography in detecting posterior lens capsule defects before traumatic cataract surgery. METHODS: This retrospective analysis includes patients with traumatic cataracts who underwent cataract surgery. Preoperative 10 MHz ultrasonography was performed to evaluate whether the posterior lens capsule was defective or intact, and the results were compared to the intraoperative findings. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and kappa were calculated. RESULTS: The study included 140 eyes of 140 patients. There were 68 eyes with closed-globe injuries and 72 eyes with open-globe injuries. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and kappa of 10 MHz ultrasonography was 86.76%, 90.28%, 89.39%, 87.84%, 88.57% and 0.771, respectively. The accuracy was 86.11% and 91.18% in open-globe and closed-globe injury groups, respectively. CONCLUSION: The accuracy of 10 MHz ultrasonography in evaluating the posterior lens capsule in traumatic cataracts is high. Preoperative 10 MHz ultrasonography would help to make an appropriate surgical plan.
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BACKGROUND/AIM: To assess the refractive outcomes of secondary intraocular lenses (IOL) in patients with traumatic aphakic eyes with corneal penetrating injury and compare different corneal curvature measurement methods. METHODS: Patients with unilateral penetrating eye injuries underwent corneal wound repair and cataract extraction, followed by secondary IOL implantation. Corneal curvature measurements were taken on the contralateral healthy eye (Group A), from the affected eye before removing corneal sutures (Group B), or after suture removal (Group C). The refractive outcomes were compared among the three groups. RESULTS: The study included 261 eyes. The Mean Absolute Error (MAE) in Group C (0.99 ± 0.85 D) was significantly smaller than that in Group A (1.87 ± 1.71 D) and Group B (1.37 ± 1.20 D) (both P < 0.001). Moreover, the percentage of eyes with IOL prediction errors within ± 0.50 D in Group C (40%) was higher than that in group A (21.7%) (OR = 2.364, 95%CI: 1.272-4.392, P = 0.006) and group B (28.0%) (OR = 1.714, 95%CI: 0.948-3.099, P = 0.073), and the percentage of eyes with IOL prediction errors within ± 1.0 D in Group C (90.9%) was higher than that in group A (67.9%) (OR = 4.758, 95%CI: 2.131-10.626, P < 0.001) and group B (75.0%) (OR = 3.370, 95%CI: 1.483-7.660, P = 0.003) as well. CONCLUSIONS: In traumatic aphakic eyes with corneal sutures, IOL power calculation based on the corneal curvature of the injured eye after removing the corneal sutures yields the best refractive outcomes.
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Córnea , Lesões da Córnea , Implante de Lente Intraocular , Refração Ocular , Acuidade Visual , Humanos , Feminino , Masculino , Implante de Lente Intraocular/métodos , Adulto , Pessoa de Meia-Idade , Lesões da Córnea/diagnóstico , Lesões da Córnea/cirurgia , Lesões da Córnea/etiologia , Lesões da Córnea/complicações , Refração Ocular/fisiologia , Córnea/cirurgia , Córnea/patologia , Estudos Retrospectivos , Adulto Jovem , Adolescente , Lentes Intraoculares , Ferimentos Oculares Penetrantes/cirurgia , Ferimentos Oculares Penetrantes/diagnóstico , Ferimentos Oculares Penetrantes/complicações , Afacia Pós-Catarata/cirurgia , Afacia Pós-Catarata/fisiopatologia , Idoso , Afacia/cirurgia , Afacia/diagnóstico , Afacia/fisiopatologia , Extração de Catarata/métodos , Topografia da Córnea/métodos , CriançaRESUMO
Both Warrensburg (WS) and Marfan syndrome (MFS) can impair the vision. Here, we recruited a Chinese family consisting of two WS affected individuals (II:1 and III:3) and five MFS affected individuals( I:1, II:2, III:1, III:2, and III:5) as well as one suspected MFS individual (II:4). Using whole exome sequencing (WES) and subsequent PCR-Sanger sequencing, we identified one novel heterozygous variant NM_000438 (PAX3) c.208 T > C, (p.Cys70Arg) from individuals with WS and one previous reported variant NM_000138 (FBN1) c.2740 T > A, (p.Cys914Ser) from individuals with MFS and co-segregated with the diseases. Real-time PCR and Western blot assay showed that, compared to their wild-type, both mRNAs and proteins of PAX3 and FBN1 mutants reduced in HKE293T cells. Together, our study identified two disease-causing variants in a same Chinese family with WS and MFS, and confirmed their damaged effects on their genes' expression. Therefore, those findings expand the mutation spectrum of PAX3 and provide a new perspective for the potential therapy.
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Síndrome de Marfan , Humanos , Síndrome de Marfan/genética , Sequenciamento do Exoma , População do Leste Asiático , Mutação , Heterozigoto , Linhagem , Fator de Transcrição PAX3/genética , Fibrilina-1/genéticaRESUMO
The long-range magnetic ordering in frustrated magnetic systems is stabilized by coupling magnetic moments to various degrees of freedom, for example, by enhancing magnetic anisotropy via lattice distortion. Here, the unconventional spin-lattice coupled metamagnetic properties of atomically-thin CrOCl, a van der Waals antiferromagnet with inherent magnetic frustration rooted in the staggered square lattice, are reported. Using temperature- and angle-dependent tunneling magnetoconductance (TMC), in complementary with magnetic torque and first-principles calculations, the antiferromagnetic (AFM)-to-ferrimagnetic (FiM) metamagnetic transitions (MTs) of few-layer CrOCl are revealed to be triggered by collective magnetic moment flipping rather than the established spin-flop mechanism, when external magnetic field (H) enforces a lattice reconstruction interlocked with the five-fold periodicity of the FiM phase. The spin-lattice coupled MTs are manifested by drastic jumps in TMC, which show anomalous upshifts at the transition thresholds and persist much higher above the AFM Néel temperature. While the MTs exhibit distinctive triaxial anisotropy, reflecting divergent magnetocrystalline anisotropy of the c-axis AFM ground state, the resulting FiM phase has an a-c easy plane in which the magnetization axis is freely rotated by H. At the 2D limit, such a field-tunable FiM phase may provide unique opportunities to explore exotic emergent phenomena and novel spintronics devices.
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RESEARCH QUESTION: Is it possible to develop a quantitative method for detecting parental DNA contamination in conventional IVF using preimplantation genetic testing for aneuploidy (PGT-A)? DESIGN: In this study, a quantification method was established for the parental contamination test (qPCT), which ensured more reliable results, and then verified its effectiveness for vitrified conventional IVF embryos. A total of 120 surplus vitrified blastocysts from patients who underwent prior routine IVF cycles were available for study. RESULTS: The results of the prospective clinical study of qPCT-PGT-A showed that the maternal contamination rate was 0.83% (1/120) and that the risk of paternal contamination was negligible. The 24 frozen embryo transfer cycles resulted in 16 clinical pregnancies, including 13 live births, one late inevitable miscarriage and two ongoing pregnancies. CONCLUSIONS: The risk of PGT in embryos with potential parental contamination is relatively low, and PGT-A is applicable for vitrified conventional IVF embryos.
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Diagnóstico Pré-Implantação , Gravidez , Masculino , Feminino , Humanos , Diagnóstico Pré-Implantação/métodos , Estudos Prospectivos , Testes Genéticos/métodos , Aneuploidia , Blastocisto , Pais , Pai , Fertilização in vitro/métodosRESUMO
BACKGROUND: The two-child policy implemented in China resulted in a surge of high-risk pregnancies among advanced maternal aged women and presented a window of opportunity to identify a large number of placenta accreta spectrum (PAS) cases, which often invoke severe blood loss and hysterectomy. We thus had an opportunity to evaluate the surgical outcomes of a unique conservative PAS management strategy for uterus preservation, and the impacts of magnetic resonance imaging (MRI) in PAS surgical planning. METHODS: Cross-sectional study, comparing the outcomes of a new uterine artery ligation combined with clover suturing technique (UAL + CST) with the existing conservative surgical approaches in a maternal public hospital with an annual birth of more than 20,000 neonates among all placenta previa cases suspecting of PAS between January 1, 2015 and December 31, 2018. RESULTS: From a total of 89,397 live births, we identified 210 PAS cases from 400 singleton pregnancies with placenta previa. Aside from 2 self-requested natural births (low-lying placenta), all PAS cases had safe cesarean deliveries without any total hysterectomy. Compared with the existing approaches, the evaluated UAL + CST had a significant reduction in intraoperative blood loss (ß=-312 ml, P < .001), RBC transfusion (ß=-1.08 unit, P = .001), but required more surgery time (ß = 16.43 min, P = .01). MRI-measured placenta thickness, when above 50 mm, can increase blood loss (ß = 315 ml, P = .01), RBC transfusion (ß = 1.28 unit, P = .01), surgery time (ß = 48.84 min, P < .001) and hospital stay (ß = 2.58 day, P < .001). A majority of percreta patients resumed normal menstrual cycle within 12 months with normal menstrual fluid volume, without abnormal urination or defecation. CONCLUSIONS: A conservative surgical management approach of UAL + CST for PAS is safe and effective with a low complication rate. MRI might be useful for planning PAS surgery. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2000035202.
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Placenta Acreta , Placenta Prévia , Idoso , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Transversais , Placenta Acreta/cirurgia , Placenta Prévia/cirurgia , Estudos Retrospectivos , Útero/diagnóstico por imagem , Útero/cirurgiaRESUMO
PURPOSE: To conduct a retrospective evaluation of a large clinical implementation of combined pulse oximeter (POX) and cardiac auscultation as a fast-screening device for congenital heart disease (CHD). METHODS: Every newborn in a large maternity healthcare center received auscultation and POX screening within 24 hours after delivery. When an abnormal heart murmur or SpO2 level was detected, an echocardiogram was ordered to confirm the diagnosis of CHD. RESULTS: From January 1, 2018 to December 31, 2019, there were 44,147 livebirths at the studied hospital where 498 suspected CHD were identified: 27 newborns by POX screening and 471 by cardiac auscultation. The diagnosis was further confirmed in 458 neonates through echocardiogram. This result put forth an overall diagnosis rate of 92.0%. Cardiac auscultation detected the majority of CHD cases 438 (95.6%) while POX only screened 20 (4.4%) cases. Interestingly, no CHD case was detected by both auscultation examination and POX screening. Auscultation detected most of the common types of CHD, but POX excelled in identifying rare and critical cases. POX screening alone had a very low accuracy of 74.07% in positive predict value (PPV). On the other hand, auscultation functioned well in terms of PPV and negative predict value (NPV) (92.99 and 99.95%, respectively), but the addition of POX improved the overall screening performance resulting in 100% NPV. We also validate the finding with the data 6 months after the study period. CONCLUSION: Our study demonstrated that addition of pulse oximetry to routine cardiac auscultation could be used as an accurate and feasible screening for early screening of CHD in newborns in large-scale clinical practice.
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Cardiopatias Congênitas , Triagem Neonatal , Auscultação , Feminino , Cardiopatias Congênitas/diagnóstico , Humanos , Recém-Nascido , Triagem Neonatal/métodos , Oximetria/métodos , Gravidez , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Sentinel lymph node biopsy (SLNB) plays an essential role in the evaluation of lymph node (LN) metastasis status and the extent of LN dissection in gastric cancer. The aim of our study was to perform a systematic review and meta-analysis for corresponding identification rate and sensitivity of different SLNB techniques. METHODS: Systematic search using PubMed, Embase, and Cochrane library databases was conducted for studies on SLNB in patients with gastric cancer. Studies were stratified according to the sentinel lymph node (SLN) biopsy technique: blue dye (BD), radiocolloid tracer (RI), indocyanine green (ICG), a combination of radiocolloid with blue dye (RI + BD), and a combination of radiocolloid with ICG (RI + ICG). A random-effect model was used to pool the identification rate, sensitivity, and accuracy. RESULTS: A total of 54 eligible studies (3767 patients) was included. The pooled identification rates of SLNB using BD, RI, ICG, RI + BD, RI + ICG were 95% (95%CI: 92-97%), 95% (95%CI: 93-97%), 99% (95%CI: 97-99%), 97% (95%CI: 96-98%), and 95% (95%CI: 87-99%), respectively. The pooled sensitivities were 82% (95%CI: 77-86%), 87% (95%CI: 81-92%), 90% (95%CI: 82-95%), 89% (95%CI: 84-93%), and 88% (95%CI: 79-94%), respectively. The pooled accuracies were 94% (95%CI: 91-96%), 95% (95%CI: 92-97%), 98% (95%CI: 95-99%), 97% (95%CI: 95-99%), and 98% (95%CI: 95-99%), respectively. CONCLUSIONS: The current meta-analysis provides reliable evidence that favors the use of ICG and dual tracer method (RI + BD/ICG) for the identification of the SLN. Considering the high costs and potential biohazard of using radioactive substances in dual tracer method, performing SLNB with ICG is the technique of choice for experienced surgeons.
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Neoplasias da Mama , Linfonodo Sentinela , Neoplasias Gástricas , Corantes , Feminino , Humanos , Verde de Indocianina , Linfonodos/diagnóstico por imagem , Metanálise como Assunto , Linfonodo Sentinela/diagnóstico por imagem , Biópsia de Linfonodo Sentinela , Neoplasias Gástricas/diagnóstico por imagem , Revisões Sistemáticas como AssuntoRESUMO
Periodontal ligament (PDL) stem cell properties are critical in the periodontal tissue regeneration for periodontitis. Previously, we have demonstrated that cigarette smoking attenuates PDL-derived stem cell (PDLSC) regenerative properties. Here, we report the findings on the regenerative properties of human PDLSCs with different donor ages and the underlying mechanisms. Human PDLSCs from 18 independent donors were divided into different age groups (≤ 20, 20-40, and > 40 years old). The proliferation of PDLSCs with donor age of ≤ 20 years old was significantly higher than that of the 20-40- and > 40-years-old groups, whereas the migration of PDLSCs with donor age of ≤ 20 and 20-40 years old was significantly higher than that of the > 40-years-old group. Moreover, the mesodermal lineage differentiation capabilities of PDLSCs were also higher in the donor age group of ≤ 20 years old than the donor age of > 40 years old. In addition, shorter telomere length and lower expression of SSEA4 were found in PDLSCs with donor age of > 40 years old, compared with those with donor age of ≤ 20-years-old group. Besides, PDLSCs with donor age of 20-40 and > 40 years old had higher IL6 and CXCL8 gene expressions. In summary, results from this study revealed the attenuated proliferation, migration, and mesodermal lineage differentiation properties in human PDLSCs with older donor ages. Donor age of PDLSCs should be considered as the selection criteria for the periodontal tissue regeneration treatment.
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Fatores Etários , Periodontite Crônica/terapia , Ligamento Periodontal/citologia , Antígenos Embrionários Estágio-Específicos/metabolismo , Células-Tronco/citologia , Telômero/ultraestrutura , Adulto , Proliferação de Células , Células Cultivadas , Feminino , Regeneração Tecidual Guiada Periodontal , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Osteogênese , Adulto JovemRESUMO
Cataracts are a significant public health problem with no proven methods for prevention. Discovery of novel disease mechanisms to delineate new therapeutic targets is of importance in cataract prevention and therapy. Herein, we report that mutations in the RagA GTPase (RRAGA), a key regulator of the mechanistic rapamycin complex 1 (mTORC1), are associated with autosomal dominant cataracts. We performed whole exome sequencing in a family with autosomal dominant juvenile-onset cataracts, and identified a novel p.Leu60Arg mutation in RRAGA that co-segregated with the disease, after filtering against the dbSNP database, and at least 123,000 control chromosomes from public and in-house exome databases. In a follow-up direct screening of RRAGA in another 22 families and 142 unrelated patients with congenital or juvenile-onset cataracts, RRAGA was found to be mutated in two unrelated patients (p.Leu60Arg and c.-16G>A respectively). Functional studies in human lens epithelial cells revealed that the RRAGA mutations exerted deleterious effects on mTORC1 signaling, including increased relocation of RRAGA to the lysosomes, up-regulated mTORC1 phosphorylation, down-regulated autophagy, altered cell growth or compromised promoter activity. These data indicate that the RRAGA mutations, associated with autosomal dominant cataracts, play a role in the disease by acting through disruption of mTORC1 signaling.
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Catarata/genética , Células Epiteliais/patologia , Cristalino/patologia , Proteínas Monoméricas de Ligação ao GTP/genética , Complexos Multiproteicos/genética , Serina-Treonina Quinases TOR/genética , Adolescente , Adulto , Autofagia/genética , Sequência de Bases , Proliferação de Células/genética , Análise Mutacional de DNA , Exoma/genética , Feminino , Humanos , Cristalino/citologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Pessoa de Meia-Idade , Complexos Multiproteicos/metabolismo , Análise de Sequência de DNA , Serina-Treonina Quinases TOR/metabolismo , Adulto JovemRESUMO
This study aimed to determine the antibacterial mechanism of cinnamaldehyde fumigation in Escherichia coli (E. coli). Through vapour fumigation, cinnamaldehyde was confirmed to exhibit effective antibacterial activity against E. coli. The minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) were 0.25 µL/mL and 0.5 µL/mL, respectively. Based on transmission electron microscopy, the wrinkled bacterial cells observed after fumigation could be related to the leakage of intracellular substances. Laser tweezers Raman spectroscopy revealed changes in the main chain of proteins, the hydrogen bond system and spatial structure, and single- and double-stranded DNA breaks. In addition, breakage of the fatty acyl chain backbone was found to affect the vertical order degree of the lipid bilayer and cell membrane fluidity, thereby inhibiting the growth of E. coli. Overall, our findings indicate that cinnamaldehyde fumigation inhibits E. coli growth by inducing changes in intracellular biological macromolecules.
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BACKGROUND: Large language models (LLMs), such as ChatGPT, have considerable implications for various medical applications. However, ChatGPT's training primarily draws from English-centric internet data and is not tailored explicitly to the medical domain. Thus, an ophthalmic LLM in Chinese is clinically essential for both healthcare providers and patients in mainland China. METHODS: We developed an LLM of ophthalmology (MOPH) using Chinese corpora and evaluated its performance in three clinical scenarios: ophthalmic board exams in Chinese, answering evidence-based medicine-oriented ophthalmic questions and diagnostic accuracy for clinical vignettes. Additionally, we compared MOPH's performance to that of human doctors. RESULTS: In the ophthalmic exam, MOPH's average score closely aligned with the mean score of trainees (64.7 (range 62-68) vs 66.2 (range 50-92), p=0.817), but achieving a score above 60 in all seven mock exams. In answering ophthalmic questions, MOPH demonstrated an adherence of 83.3% (25/30) of responses following Chinese guidelines (Likert scale 4-5). Only 6.7% (2/30, Likert scale 1-2) and 10% (3/30, Likert scale 3) of responses were rated as 'poor or very poor' or 'potentially misinterpretable inaccuracies' by reviewers. In diagnostic accuracy, although the rate of correct diagnosis by ophthalmologists was superior to that by MOPH (96.1% vs 81.1%, p>0.05), the difference was not statistically significant. CONCLUSION: This study demonstrated the promising performance of MOPH, a Chinese-specific ophthalmic LLM, in diverse clinical scenarios. MOPH has potential real-world applications in Chinese-language ophthalmology settings.
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The discovery of various primary ferroic phases in atomically-thin van der Waals crystals have created a new two-dimensional wonderland for exploring and manipulating exotic quantum phases. It may also bring technical breakthroughs in device applications, as evident by prototypical functionalities of giant tunneling magnetoresistance, gate-tunable ferromagnetism and non-volatile ferroelectric memory etc. However, two-dimensional multiferroics with effective magnetoelectric coupling, which ultimately decides the future of multiferroic-based information technology, has not been realized yet. Here, we show that an unconventional magnetoelectric coupling mechanism interlocked with heterogeneous ferrielectric transitions emerges at the two-dimensional limit in van der Waals multiferroic CuCrP2S6 with inherent antiferromagnetism and antiferroelectricity. Distinct from the homogeneous antiferroelectric bulk, thin-layer CuCrP2S6 under external electric field makes layer-dependent heterogeneous ferrielectric transitions, minimizing the depolarization effect introduced by the rearrangements of Cu+ ions within the ferromagnetic van der Waals cages of CrS6 and P2S6 octahedrons. The resulting ferrielectric phases are characterized by substantially reduced interlayer magnetic coupling energy of nearly 50% with a moderate electric field of 0.3 V nm-1, producing widely-tunable magnetoelectric coupling which can be further engineered by asymmetrical electrode work functions.
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Purpose: To evaluate the refractive status and ocular biometric parameters in primary angle-closure glaucoma (PACG) eyes with different axial lengths (ALs). Methods: In total, 742 Chinese PACG subjects with complete ophthalmic examinations were enrolled. The refractive status was categorized as myopia (spherical equivalent [SE] ≤-0.5 D), emmetropia (-0.5 D < SE < +0.5 D), and hyperopia (SE ≥+0.5 D), whereas the AL was divided into short (AL <22.5 mm), regular (22.5 ≤ AL <23.5 mm), and long (AL ≥23.5 mm). The refractive status and ocular biometric parameters were compared among different AL groups. Results: The mean AL of the PACG eyes was 22.53 ± 0.84 mm (range: 19.68-25.57 mm). The refractive status was significantly different among different AL groups (P < 0.001). Also, 92.6% of hyperopic PACG eyes showed AL <23.5 mm, and 19.0% of myopic PACG eyes showed AL ≥23.5 mm. The SE showed significant differences among different AL groups only in the hyperopic subjects (P = 0.012). The AL was significantly longer in myopic eyes (P < 0.001). The PACG eyes with longer AL exhibited lower keratometry, longer central anterior chamber depth and corneal diameter, and lens position and relative lens position closer to the anterior (P < 0.001). Conclusion: Axial hyperopia was common in PACG eyes, and axial myopia was not uncommon. Relatively anterior lens position could explain the occurrence of PACG in the eyes with long AL.
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Glaucoma de Ângulo Fechado , Hiperopia , Cristalino , Miopia , Humanos , Hiperopia/diagnóstico , Glaucoma de Ângulo Fechado/diagnóstico , Refração Ocular , Miopia/complicações , Miopia/diagnóstico , Córnea , Biometria , Câmara Anterior/diagnóstico por imagemRESUMO
Ferroptosis is a newly discovered type of cell death mainly triggered by uncontrolled lipid peroxidation, and it could potentially have a significant impact on the development and progression of tetralogy of Fallot (TOF). Our project aims to identify and validate potential genes related to ferroptosis in TOF. We obtained sequencing data of TOF from the GEO database and ferroptosis-related genes from the ferroptosis database. We employed bioinformatics methods to analyze the differentially expressed mRNAs (DEmRNAs) and microRNAs between the normal control group and TOF group and identify DEmRNAs related to ferroptosis. Protein-protein interaction analysis was conducted to screen hub genes. Furthermore, a miRNA-mRNA-TF co-regulatory network was constructed to utilize prediction software. The expression of hub genes was further validated through quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). After conducting the differential gene analysis, we observed that in TOF, 41 upregulated mRNAs and three downregulated mRNAs associated with ferroptosis genes were found. Further Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis revealed that these genes were primarily involved in molecular functions and biological processes related to chemical stress, oxidative stress, cellular response to starvation, response to nutrient levels, cellular response to external stimulus, and cellular response to extracellular stimulus. Furthermore, we constructed a miRNA-mRNA-TF co-regulatory network. qRT-PCR analysis of the right ventricular tissues from human cases showed an upregulation in the mRNA levels of KEAP1 and SQSTM1. Our bioinformatics analysis successfully identified 44 potential genes that are associated with ferroptosis in TOF. This finding significantly contributes to our understanding of the molecular mechanisms underlying the development of TOF. Moreover, these findings have the potential to open new avenues for the development of innovative therapeutic approaches for the treatment of this condition.
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Non-adherent culture is critical for the transdifferentiation of stem cells from mesoderm to neuroectoderm. Sphere culture has been reported to directly induce the adipose tissue cells to neural stem cells. Here we aimed to evaluate continuous non-adherent culture on the transdifferentiation potential of human adipose-derived stem cells (ASCs) into retinal lineage. Human ASCs were induced into retinal lineage by the treatment of noggin, dickkopf-related protein 1, and IGF-1 (NDI) under adherent and non-adherent culture. The NDI induction treatment with the adherent culture for 21 days promoted robust expression of retinal markers in the induced ASCs as compared to those without NDI induction on the adherent culture. With continuous non-adherent culture for 21 days, human ASCs could highly express retinal marker genes even without NDI induction treatment as compared to those on the adherent culture. The combination of continuous non-adherent culture with the NDI induction did not show a significant upregulation of the retinal marker expression as compared to either NDI induction with the adherent culture or continuous non-adherent culture without NDI induction treatment. In summary, both non-adherent culture and NDI induction medium could independently promote the transdifferentiation of human ASCs into retinal lineage. Yet, their combination did not produce an enhancement effect.
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This study aimed to evaluate the association of body mass index (BMI) and the weight-related gene, peroxidasin-like (PXDNL), with acute primary angle closure (APAC) and primary angle-closure glaucoma (PACG) in southern Chinese population. Total 4700 study subjects (1024 APAC, 781 PACG, and 2895 control subjects) with complete ophthalmic examinations were enrolled into this study. The association of BMI with APAC, PACG and ocular biometric parameters was evaluated. Three PXDNL missense variants were genotyped by TaqMan assay, and their association with APAC and PACG was also investigated. Multivariable logistic regression analysis showed that BMI and body weight were significantly associated with both APAC and PACG (P < 0.01). Multiple linear regression analysis demonstrated that each 1 kg/m2 increased in BMI was associated with 0.038 mm increase in axial length, 0.018 mm increase in central anterior chamber depth, 0.002 mm increase in lens position, 0.012 mm increase in corneal diameter and 0.014 mm decrease in lens thickness among the APAC subjects (P < 0.001), but not with PACG. Genetic association analysis identified that PXDNL rs11985241-rs16916207 CT haplotype conferred a higher risk to APAC (OR = 1.25, P = 0.004) than the TG haplotype, but not with PACG. The APAC subjects carrying the rs11985241 C or rs16916207 T alleles showed significantly lower weight than those carrying the corresponding protective alleles. In summary, this study revealed that lower BMI could be associated with higher risk of APAC. PXDNL could be a new associated gene for APAC.
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PURPOSE: To identify a disease-causing paired box 6 (PAX6) gene mutation in a Chinese family affected by autosomal dominant congenital aniridia. METHODS: All participants in the study, including the aniridia family and 100 unrelated senile cataract controls, received a comprehensive ophthalmic examination. Genomic DNA was extracted from their whole blood. Mutation screen in all exons and their adjacent splicing junctions of PAX6 was performed by direct sequencing of polymerase chain reaction (PCR) products. PCR products of heterozygous mutation were further cloned into T-vectors and confirmed by sequencing. Multiple alignments were performed using ClustalX to compare PAX6 protein sequences among vertebrates. MicroRNA binding sites were predicted by TargetScan. RESULTS: A novel heterozygous PAX6 deletion c.1251_1353del103 (p.Pro418Serfs*87) affecting exon 14 and the 3'-untranslated-region (3'-UTR) was identified in the congenital aniridia family. The mutation was exclusively observed in all affected family members but not in any unaffected family member or unrelated control. Bioinformatics analysis showed that the deletion led to remarkable changes of the PAX6 protein, including a frameshift, changes of protein sequence, and a COOH-terminal extension. Multiple alignments showed that the affected region of PAX6 shared high sequence identity (100%) among its vertebrate orthologs. The COOH-terminal extension might also affect microRNA binding sites in the 3'-UTR as predicted by TargetScan. CONCLUSIONS: In the current study we reported a novel PAX6 deletion resulting in an abnormal PAX6 COOH-terminal extension in the Chinese family affected by aniridia. Our findings thus add to the mutation spectrum of PAX6.
Assuntos
Aniridia/genética , Povo Asiático/genética , Proteínas do Olho/genética , Proteínas de Homeodomínio/genética , Fatores de Transcrição Box Pareados/genética , Proteínas de Ligação a RNA/genética , Proteínas Repressoras/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Estudos de Casos e Controles , Criança , Pré-Escolar , Éxons , Mutação da Fase de Leitura , Genes Dominantes , Heterozigoto , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Dados de Sequência Molecular , Fator de Transcrição PAX6 , Linhagem , Proteínas de Ligação a RNA/metabolismo , Alinhamento de SequênciaRESUMO
BACKGROUND: To date, studies on the role played by cigarette smoking in primary open-angle glaucoma (POAG) remains controversial. The current study evaluated cigarette smoking as a risk factor of POAG and its relationships with vertical cup-to-disc ratio (VCDR), central corneal thickness (CCT) and intraocular pressure (IOP) in a Chinese cohort. METHODS: In a total of 248 unrelated individuals including 30 juvenile-onset POAG (JOAG), 92 adult-onset POAG (AOAG) and 126 sex-matched senile cataract controls, underwent comprehensive ophthalmic examination. Their smoking was obtained and documented by questionnaire. Association of cigarette smoking with POAG was performed using logistic regression controlled for age and sex. Effects of cigarette smoking on VCDR, IOP and CCT were analyzed with multiple linear regression. RESULTS: In either JOAG or AOAG, no association of cigarette smoking was found with disease onset (P = 0.692 and 0.925 respectively). In controls and JOAG, no significant effects of smoking were found on VCDR, IOP or CCT (all P > 0.05). Smoking was found to be correlated with decreased CCT in AOAG and combined POAG (JOAG + AOAG) (P = 0.009 and 0.003), but no association with VCDR or IOP was observed (P > 0.05). CONCLUSIONS: Although cigarette smoking was not found to be risk factor for onset of POAG, it was correlated with CCT in AOAG, and thus might still play a role in the disease course, especially for AOAG.