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1.
BMC Oral Health ; 24(1): 611, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802844

RESUMO

PURPOSE: This study aims to elucidate the biological functions of ferroptosis-related genes in periodontitis, along with their correlation to tumor microenvironment (TME) features such as immune infiltration. It aims to provide potential diagnostic markers of ferroptosis for clinical management of periodontitis. METHODS: Utilizing the periodontitis-related microarray dataset GSE16134 from the Gene Expression Omnibus (GEO) and a set of 528 ferroptosis-related genes identified in prior studies, this research unveils differentially expressed ferroptosis-related genes in periodontitis. Subsequently, a protein-protein interaction network was constructed. Subtyping of periodontitis was explored, followed by validation through immune cell infiltration and gene set enrichment analyses. Two algorithms, randomForest and SVM(Support Vector Machine), were employed to reveal potential ferroptosis diagnostic markers for periodontitis. The diagnostic efficacy, immune correlation, and potential transcriptional regulatory networks of these markers were further assessed. Finally, potential targeted drugs for differentially expressed ferroptosis markers in periodontitis were predicted. RESULTS: A total of 36 ferroptosis-related genes (30 upregulated, 6 downregulated) were identified from 829 differentially expressed genes between 9 periodontitis samples and the control group. Subsequent machine learning algorithm screening highlighted 4 key genes: SLC1A5(Solute Carrier Family 1 Member 5), SLC2A14(Solute Carrier Family 1 Member 14), LURAP1L(Leucine Rich Adaptor Protein 1 Like), and HERPUD1(Homocysteine Inducible ER Protein With Ubiquitin Like Domain 1). Exploration of these 4 key genes, supported by time-correlated ROC analysis, demonstrated reliability, while immune infiltration results indicated a strong correlation between key genes and immune factors. Furthermore, Gene Set Enrichment Analysis (GSEA) was conducted for the four key genes, revealing enrichment in GO/KEGG pathways that have a significant impact on periodontitis. Finally, the study predicted potential transcriptional regulatory networks and targeted drugs associated with these key genes in periodontitis. CONCLUSIONS: The ferroptosis-related genes identified in this study, including SLC1A5, SLC2A14, LURAP1L, and HERPUD1, may serve as novel diagnostic and therapeutic targets for periodontitis. They are likely involved in the occurrence and development of periodontitis through mechanisms such as immune infiltration, cellular metabolism, and inflammatory chemotaxis, potentially linking the ferroptosis pathway to the progression of periodontitis. Targeted drugs such as flurofamide, L-733060, memantine, tetrabenazine, and WAY-213613 hold promise for potential therapeutic interventions in periodontitis associated with these ferroptosis-related genes.


Assuntos
Ferroptose , Periodontite , Ferroptose/genética , Humanos , Periodontite/genética , Mapas de Interação de Proteínas/genética , Redes Reguladoras de Genes , Biomarcadores/metabolismo
2.
Nat Commun ; 15(1): 3173, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609390

RESUMO

Semaphorin-3A (SEMA3A) functions as a chemorepulsive signal during development and can affect T cells by altering their filamentous actin (F-actin) cytoskeleton. The exact extent of these effects on tumour-specific T cells are not completely understood. Here we demonstrate that Neuropilin-1 (NRP1) and Plexin-A1 and Plexin-A4 are upregulated on stimulated CD8+ T cells, allowing tumour-derived SEMA3A to inhibit T cell migration and assembly of the immunological synapse. Deletion of NRP1 in both CD4+ and CD8+ T cells enhance CD8+ T-cell infiltration into tumours and restricted tumour growth in animal models. Conversely, over-expression of SEMA3A inhibit CD8+ T-cell infiltration. We further show that SEMA3A affects CD8+ T cell F-actin, leading to inhibition of immune synapse formation and motility. Examining a clear cell renal cell carcinoma patient cohort, we find that SEMA3A expression is associated with reduced survival, and that T-cells appear trapped in SEMA3A rich regions. Our study establishes SEMA3A as an inhibitor of effector CD8+ T cell tumour infiltration, suggesting that blocking NRP1 could improve T cell function in tumours.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Animais , Humanos , Actinas , Linfócitos T CD8-Positivos , Citoesqueleto , Semaforina-3A/genética
4.
Nat Immunol ; 25(5): 834-846, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38561495

RESUMO

Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.


Assuntos
Antígenos CD , Apirase , Cadeias alfa de Integrinas , Receptores de Antígenos de Linfócitos T , Transdução de Sinais , Animais , Humanos , Camundongos , Antígenos CD/metabolismo , Antígenos CD/imunologia , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Cadeias alfa de Integrinas/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias/imunologia , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/imunologia , Linfócitos T Citotóxicos/imunologia
5.
Heliyon ; 10(3): e25459, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38333863

RESUMO

Glucose is a sugar crucial for human health since it participates in many biochemical reactions. It produces adenosine 5'-triphosphate (ATP) and nucleosides through glucose metabolic and pentose phosphate pathways. These processes require many transporter proteins to assist in transferring glucose across cells, and the most notable ones are glucose transporter-2 (GLUT-2) and sodium/glucose cotransporter 1 (SGLT1). Glucose enters small intestinal epithelial cells from the intestinal lumen by crossing the brush boundary membrane via the SGLT1 cotransporter. It exits the cells by traversing the basolateral membrane through the activity of the GLUT-2 transporter, supplying energy throughout the body. Dysregulation of these glucose transporters is involved in the pathogenesis of several metabolic diseases, such as diabetes. Natural loss of GLUT-2 or its downregulation causes abnormal blood glucose concentrations in the body, such as fasting hypoglycemia and glucose tolerance. Therefore, understanding GLUT-2 physiology is necessary for exploring the mechanisms of diabetes and targeted treatment development. This article reviews how the apical GLUT-2 transporter maintains normal physiological functions of the human body and the adaptive changes this transporter produces under pathological conditions such as diabetes.

6.
Br J Ophthalmol ; 108(3): 424-431, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36878715

RESUMO

BACKGROUND/AIMS: This study evaluates the performance of the Airdoc retinal artificial intelligence system (ARAS) for detecting multiple fundus diseases in real-world scenarios in primary healthcare settings and investigates the fundus disease spectrum based on ARAS. METHODS: This real-world, multicentre, cross-sectional study was conducted in Shanghai and Xinjiang, China. Six primary healthcare settings were included in this study. Colour fundus photographs were taken and graded by ARAS and retinal specialists. The performance of ARAS is described by its accuracy, sensitivity, specificity and positive and negative predictive values. The spectrum of fundus diseases in primary healthcare settings has also been investigated. RESULTS: A total of 4795 participants were included. The median age was 57.0 (IQR 39.0-66.0) years, and 3175 (66.2%) participants were female. The accuracy, specificity and negative predictive value of ARAS for detecting normal fundus and 14 retinal abnormalities were high, whereas the sensitivity and positive predictive value varied in detecting different abnormalities. The proportion of retinal drusen, pathological myopia and glaucomatous optic neuropathy was significantly higher in Shanghai than in Xinjiang. Moreover, the percentages of referable diabetic retinopathy, retinal vein occlusion and macular oedema in middle-aged and elderly people in Xinjiang were significantly higher than in Shanghai. CONCLUSION: This study demonstrated the dependability of ARAS for detecting multiple retinal diseases in primary healthcare settings. Implementing the AI-assisted fundus disease screening system in primary healthcare settings might be beneficial in reducing regional disparities in medical resources. However, the ARAS algorithm must be improved to achieve better performance. TRIAL REGISTRATION NUMBER: NCT04592068.


Assuntos
Retinopatia Diabética , Drusas Retinianas , Pessoa de Meia-Idade , Idoso , Humanos , Feminino , Masculino , Inteligência Artificial , Estudos Transversais , Sensibilidade e Especificidade , China/epidemiologia , Retinopatia Diabética/diagnóstico , Atenção Primária à Saúde , Programas de Rastreamento
7.
Retina ; 44(4): 680-688, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38011844

RESUMO

PURPOSE: To investigate the effectiveness of two regimens of ranibizumab-assisted pars plana vitrectomy in the treatment of patients with proliferative diabetic retinopathy. METHODS: This is a prospective, 6-month, randomized controlled trial. Eighty patients with 87 eyes requiring pars plana vitrectomy treatment for proliferative diabetic retinopathy were included and randomly divided into a 1.0-mg injection group and a 0.5-mg injection group. The ranibizumab was delivered intraoperatively, at the close of surgery. The vitreous hemorrhage grade, best-corrected visual acuity, central macular thickness, and safety data were assessed to Month 6. RESULTS: The 1.0-mg injection group had a milder grade and a lower reoccurrence rate of early postoperatively vitreous hemorrhage than the 0.5-mg injection group (35.0% and 63.4%, respectively, P = 0.0195). The mean best-corrected visual acuity of two groups was significantly improved from baseline to 6 months after surgery, 1.60 ± 0.72 Logarithm of the Minimum Angle of Resolution (LogMAR) (<20/200) to 0.47 ± 0.49 LogMAR (20/59) for the 1.0-mg injection group and 1.51 ± 0.69 LogMAR (<20/200) to 0.50 ± 0.31 LogMAR (20/63) for the 0.5-mg injection group, but there was no significant difference between the two groups ( P = 0.74). There was no significant difference in the mean decrease in central macular thickness and probability of postoperative adverse events between the two groups. CONCLUSION: Intravitreal injection of 1.0 mg of ranibizumab after pars plana vitrectomy compared with the recommended dose of 0.5 mg significantly reduced the recurrence and severity of early postoperative vitreous hemorrhage in patients with proliferative diabetic retinopathy. It also contributed to the early recovery of visual acuity after surgery and did not increase postoperative adverse events.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/tratamento farmacológico , Injeções Intravítreas , Estudos Prospectivos , Ranibizumab/efeitos adversos , Ranibizumab/uso terapêutico , Resultado do Tratamento , Vitrectomia/efeitos adversos , Hemorragia Vítrea/cirurgia
8.
Cell Mol Immunol ; 20(11): 1300-1312, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37666955

RESUMO

Solid organ transplant (SOT) recipients receive immunosuppressive drugs (ISDs) and are susceptible to developing severe COVID-19. Here, we analyze the Spike-specific T-cell response after 3 doses of mRNA vaccine in a group of SOT patients (n = 136) treated with different ISDs. We demonstrate that a combination of a calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and prednisone (Pred) treatment regimen strongly suppressed the mRNA vaccine-induced Spike-specific cellular response. Such defects have clinical consequences because the magnitude of vaccine-induced Spike-specific T cells was directly proportional to the ability of SOT patients to rapidly clear SARS-CoV-2 after breakthrough infection. To then compensate for the T-cell defects induced by immunosuppressive treatment and to develop an alternative therapeutic strategy for SOT patients, we describe production of 6 distinct SARS-CoV-2 epitope-specific ISD-resistant T-cell receptor (TCR)-T cells engineered using the mRNA electroporation method with reactivity minimally affected by mutations occurring in Beta, Delta, Gamma, and Omicron variants. This strategy with transient expression characteristics marks an improvement in the immunotherapeutic field and provides an attractive and novel therapeutic possibility for immunosuppressed COVID-19 patients.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Linfócitos T , COVID-19/terapia , Imunossupressores/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos , Anticorpos Antivirais
9.
Int J Ophthalmol ; 16(9): 1512-1520, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37724280

RESUMO

AIM: To explore the effect of orthokeratology (OK) fitting on retinal vessel density in low to moderate myopia adolescents by using optical coherence tomography angiography. METHODS: Children aged 10 to 14y with a cycloplegic spherical equivalent refraction of -0.50 diopter (D) to -5.00 D and astigmatism with more than -1.50 D were recruited. The enrolled adolescents were divided into OK group and spectacle group. During regular follow-up, adolescents were measured respectively at pre-wear, 1, 3, and 6mo after treatment. The follow-up included uncorrected distance visual acuity (UDVA), axial length (AL), superficial capillary plexus density (SCPD), deep capillary plexus density (DCPD), central retinal thickness (CRT), foveal avascular zone area (FAZ-A), foveal avascular zone perimeter (FAZ-P) and foveal vessel density in a 300-µm-wide region around foveal avascular zone (FD-300). The collected data were analyzed using statistical methods. RESULTS: By one month, SCPD significantly increased in the fovea and superior retina, and DCPD significantly increased inferiorly in OK group compared to spectacle group (P<0.05). By three months, there were significant increases in SCPD in the fovea and inferior retina, and DCPD in the parafovea, superior, and inferior retina in OK group (P<0.05), while the increase in SCPD and DCPD in the fovea were observed by six months (P<0.05). The FD-300 significantly increased at every follow-up in OK group compared to spectacle group (P<0.05). No significant differences in the CRT, FAZ-A and FAZ-P and FD-300 were observed between two groups (P>0.05). OK group showed a significant improvement in UDVA after wearing OK, compared to spectacle group (P<0.01), while the AL did not show a significant difference between two groups (P>0.05). CONCLUSION: Short-term OK worn can increase local retinal vessel density in adolescents with low-to-moderate myopia.

10.
Graefes Arch Clin Exp Ophthalmol ; 261(12): 3415-3423, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37561145

RESUMO

PURPOSE: The aim of this study was to assess the efficacy and safety of a novel releasing-closing-tapping approach in the treatment of persistent macular holes (PMHs) after initial surgery with internal limiting membrane (ILM) peeling. METHODS: We retrospectively analyzed patients with PMHs after initial surgery with ILM peeling who were treated with a novel releasing-closing-tapping approach. After repeated pars plana vitrectomy (PPV), the surgeon effectively released the adhesion between the edges and retinal pigment epithelium (RPE) by gently scraping the retinal neuroepithelium. Then, the hole was converted into a transverse slit, and the edges were gently tapped flat so that they attached to the RPE, and no space was left under the edges. Finally, air tamponade was carried out. The primary outcome measures included MH closure and the change in best-corrected visual acuity (BCVA) from preoperatively to postoperatively. RESULTS: The study included 11 PMH patients with a mean age of 63.82 ± 3.31 years. The mean minimum linear diameter of PMHs was 666.3 ± 208.1 µm, and the mean basal diameter was 1547.2 ± 351.8 µm. MH closure was achieved in 90.9% (10/11) of eyes, with significant improvement of visual acuity from 1.19 ± 0.30 logMAR to 0.65 ± 0.29 logMAR postoperatively. CONCLUSION: The releasing-closing-tapping approach with repeated PPV is a simple, effective, and safe surgical procedure for refractory PMHs after initial surgery with ILM peeling that can significantly improve the visual outcome and achieve a high surgical success rate.


Assuntos
Membrana Epirretiniana , Perfurações Retinianas , Humanos , Pessoa de Meia-Idade , Idoso , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Membrana Epirretiniana/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Vitrectomia/métodos , Membrana Basal/cirurgia , Cadáver , Resultado do Tratamento
11.
Cell Rep ; 42(5): 112470, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37141092

RESUMO

Most existing studies characterizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses are peptide based. This does not allow evaluation of whether tested peptides are processed and presented canonically. In this study, we use recombinant vaccinia virus (rVACV)-mediated expression of SARS-CoV-2 spike protein and SARS-CoV-2 infection of angiotensin-converting enzyme (ACE)-2-transduced B cell lines to evaluate overall T cell responses in a small cohort of recovered COVID-19 patients and uninfected donors vaccinated with ChAdOx1 nCoV-19. We show that rVACV expression of SARS-CoV-2 antigen can be used as an alternative to SARS-CoV-2 infection to evaluate T cell responses to naturally processed spike antigens. In addition, the rVACV system can be used to evaluate the cross-reactivity of memory T cells to variants of concern (VOCs) and to identify epitope escape mutants. Finally, our data show that both natural infection and vaccination could induce multi-functional T cell responses with overall T cell responses remaining despite the identification of escape mutations.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , ChAdOx1 nCoV-19 , Vacinação , Anticorpos Antivirais
12.
Clinics (Sao Paulo) ; 78: 100208, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37148830

RESUMO

OBJECTIVE: Oral ulcers are a lesion in the oral mucosa that impacts chewing or drinking. Epoxyeicosatrienoic Acids (EETs) have enhanced angiogenic, regenerative, anti-inflammatory, and analgesic effects. The present study aims to evaluate the effects of 1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea (TPPU), a soluble epoxide hydrolase inhibitor for increasing EETs level, on the healing of oral ulcers. METHODS: The chemically-induced oral ulcers were established in Sprague Dawley rats. The ulcer area was treated with TPPU to evaluate the healing time and pain threshold of ulcers. The expression of angiogenesis and cell proliferation-related protein in the ulcer area was detected using immunohistochemical staining. The effects of TPPU on migration and angiogenesis capability were measured with scratch assay and tube formation. RESULTS: Compared with the control group, TPPU promoted wound healing of oral ulcers with a shorter healing time, and raised pain thresholds. Immunohistochemical staining showed that TPPU increased the expression of angiogenesis and cell proliferation-related protein with reduced inflammatory cell infiltration in the ulcer area. TPPU enhanced cell migration and tube-forming potential in vitro. CONCLUSIONS: The present results support the potential of TPPU with multiple biological effects for the treatment of oral ulcers by targeting soluble epoxide hydrolase.


Assuntos
Úlceras Orais , Ratos , Animais , Ratos Sprague-Dawley , Úlceras Orais/tratamento farmacológico , Epóxido Hidrolases/metabolismo , Úlcera , Eicosanoides , Cicatrização , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico
13.
BJUI Compass ; 4(3): 322-330, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37025470

RESUMO

Objectives: This study aimed to investigate the anti-PD-1 inhibitor pembrolizumab as a potential agent for use in non-muscle-invasive bladder cancer (NMIBC) by conducting a Phase 1 safety run-in study to assess the safety and tolerability of intravesical pembrolizumab after transurethral resection of the bladder tumour (TURBT). Patients and methods: Eligible patients had recurrent NMIBC for which adjuvant treatment post TURBT was a reasonable treatment option, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 and adequate end-organ function. Pembrolizumab was administered by intravesical instillation once weekly for a total of six doses. Intra-patient dose escalation was performed in three paired patient cohorts with doses starting at 50 mg and increasing through 100 mg to a maximum of 200 mg. Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 with dose limiting toxicity (DLT) defined as a clinically significant, drug-related, Grade 4 haematological or Grade 3 or higher non-haematological toxicity occurring within 7 days of administration of the first treatment at a given dose for that patient. Results: Six patients were treated with no DLTs seen during dose escalation. Drug-related AEs were of low grade and included dysuria and fatigue. All patients completed six doses of treatment as planned. Pharmacokinetic and pharmacodynamic assays did not detect any pembrolizumab in the serum following repeated intravesical administration, and no changes in peripheral immune cell populations were observed. Conclusions: Administration of intravesical pembrolizumab was well tolerated and did not raise any safety concerns in patients with NMIBC following TURBT. There was no evidence of systemic absorption or systemic immune effects following intravesical administration. Further studies are required to assess whether intravesical administration has anti-tumour activity.

14.
Biochem Biophys Res Commun ; 661: 75-81, 2023 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-37087801

RESUMO

Cisplatin resistance is the main reason for uveal melanoma (UM) treatment failure. Thus, developing strategy that increasing cisplatin sensitivity is needed. In this study, we performed drug repositioning analysis with the Connectivity Map database using a panel of previously identified cisplatin sensitivity-associated genes and cisplatin resistance-associated genes as the signature and obtained the antiparasitic drug selamectin. We demonstrated that the selamectin and cisplatin combination showed a synergistic effect on inhibiting UM cell growth. Experiments in tumor-bearing nude mice further showed that selamectin and cisplatin have synergistic effects in reducing tumor growth. Previous studies have linked increased autophagy with tumor resistance to chemotherapy. We found that selamectin inhibited the expression of the autophagy-related gene ATG9B, thus reducing autophagy. The cisplatin resistance-associated genes PDGFRB, DUSP1, MAST1 and IL11 were significantly downregulated in UM cells treated with selamectin. In summary, our study shows that selamectin enhanced the sensitivity of UM to cisplatin, through the mechanism of inhibiting cisplatin resistance-associated gene expression and autophagy. These findings may provide a new strategy for the treatment of UM.


Assuntos
Cisplatino , Neoplasias Uveais , Animais , Camundongos , Cisplatino/farmacologia , Camundongos Nus , Linhagem Celular Tumoral , Neoplasias Uveais/tratamento farmacológico , Autofagia
15.
Elife ; 122023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36626205

RESUMO

Virus-based tumour vaccines offer many advantages compared to other antigen-delivering systems. They generate concerted innate and adaptive immune response, and robust CD8+ T cell responses. We engineered a non-replicating pseudotyped influenza virus (S-FLU) to deliver the well-known cancer testis antigen, NY-ESO-1 (NY-ESO-1 S-FLU). Intranasal or intramuscular immunization of NY-ESO-1 S-FLU virus in mice elicited a strong NY-ESO-1-specific CD8+ T cell response in lungs and spleen that resulted in the regression of NY-ESO-1-expressing lung tumour and subcutaneous tumour, respectively. Combined administration with anti-PD-1 antibody, NY-ESO-1 S-FLU virus augmented the tumour protection by reducing the tumour metastasis. We propose that the antigen delivery through S-FLU is highly efficient in inducing antigen-specific CD8+ T cell response and protection against tumour development in combination with PD-1 blockade.


Assuntos
Inibidores de Checkpoint Imunológico , Orthomyxoviridae , Masculino , Camundongos , Animais , Antígenos de Neoplasias , Proteínas de Membrana , Imunização , Anticorpos , Linfócitos T CD8-Positivos
16.
Retina ; 43(12): 2075-2079, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35174805

RESUMO

PURPOSE: We present a new technique that allows an intraocular lens to be explanted through the small incisions used in modern cataract surgery. METHODS AND RESULTS: The intraocular lens optic is cut into three connected pieces at the 1-mm-wide end with scissors. Then, with the stabilizing counterforce provided by a pair of vitreoretinal forceps through a paracentesis, the middle piece is removed first, followed by the two side pieces connected with haptics flipped over at the connected part. These two parts overlap each other when passing through the incision, eventually resulting in the explantation of the intraocular lens, as an intact piece. CONCLUSION: We believe this method provides a simple and effective way to remove intraocular lens through very small incisions, which could also reduce complications and hasten patient's recovery.


Assuntos
Extração de Catarata , Lentes Intraoculares , Humanos , Reoperação , Remoção de Dispositivo/métodos , Olho
17.
Clin Genet ; 103(5): 529-539, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36541162

RESUMO

Thymic epithelial tumors (TETs) are rare mediastinal tumors whose tumorigenesis mechanism is poorly understood. Characterization of molecular alterations in TETs may contribute to a better understanding of tumorigenesis and prognosis. Hybrid capture-based next-generation sequencing was performed on tumor tissues from 47 TETs (39 thymomas and 8 thymic carcinomas) to detect mutations in 315 tumor-associated genes. In total, 178 nonsynonymous mutations were identified, with a median of 3.79 per tumor in 47 TETs. Higher tumor mutation burden (TMB) level was more common in older TET patients, and significantly associated with the more advanced pathological type, especially in thymic carcinomas (TC) patients. The gene mutation profiles of B1-3, A/AB, and TC patients varied greatly. In the actionable mutations analysis, we found 32 actionable mutations in 24 genes. Among them, NFKBIA and TP53 mutations was the most frequently, which were only identified in TCs. Additionally, TCGA database analysis found that the expression of NFKBIA mRNA in the TCs were significantly higher than thymomas. TET patients with high NFKBIA expression had shorter overall survival compared with patients with low/medium NFKBIA expression, thus providing insights to consider NFKBIA as a potential prognosis biomarker and therapeutic target in TETs.


Assuntos
Neoplasias Epiteliais e Glandulares , Timoma , Neoplasias do Timo , Humanos , Idoso , Timoma/genética , Timoma/patologia , Neoplasias do Timo/genética , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/patologia , Neoplasias Epiteliais e Glandulares/genética , Prognóstico , Carcinogênese , Genômica
18.
Clinics ; 78: 100208, 2023. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1447975

RESUMO

Abstract Objective Oral ulcers are a lesion in the oral mucosa that impacts chewing or drinking. Epoxyeicosatrienoic Acids (EETs) have enhanced angiogenic, regenerative, anti-inflammatory, and analgesic effects. The present study aims to evaluate the effects of 1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea (TPPU), a soluble epoxide hydrolase inhibitor for increasing EETs level, on the healing of oral ulcers. Methods The chemically-induced oral ulcers were established in Sprague Dawley rats. The ulcer area was treated with TPPU to evaluate the healing time and pain threshold of ulcers. The expression of angiogenesis and cell proliferation-related protein in the ulcer area was detected using immunohistochemical staining. The effects of TPPU on migration and angiogenesis capability were measured with scratch assay and tube formation. Results Compared with the control group, TPPU promoted wound healing of oral ulcers with a shorter healing time, and raised pain thresholds. Immunohistochemical staining showed that TPPU increased the expression of angiogenesis and cell proliferation-related protein with reduced inflammatory cell infiltration in the ulcer area. TPPU enhanced cell migration and tube-forming potential in vitro. Conclusions The present results support the potential of TPPU with multiple biological effects for the treatment of oral ulcers by targeting soluble epoxide hydrolase.

19.
Chinese Journal of School Health ; (12): 1610-1613, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-998785

RESUMO

Abstract@#Through in-depth investigation into Japanese nutrition health educators post content, configuration, training mode, advanced education practice and the difficulties, the paper explores the effective ways of integrating nutrition health education into the school health education teacher and curriculum system as well as health promotion, so as to guide teachers and students to establish a correct concept of health, enhance health literacy and develop a healthy lifestyle. Additionally, the paper aims at providing suggestions for the construction of nutrition and health school as well as the future development of nutrition health education in China.

20.
Journal of Preventive Medicine ; (12): 861-865, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-997143

RESUMO

Objective@#To investigate the effects of lactoprotein iron chelates on rats with iron deficiency anaemia (IDA), so as to provide insights into developing and utilizing novel iron supplements.@*Methods@#Seventy weaning female SPF-graded rats of the SD strain were randomly divided into the control group (A), model group (B), ferrous sulfate group (C), lactoferrin group (D), lactoferrin iron chelate group (E), Casein oligopeptide iron chelate group (F) and whey protein oligopeptide iron chelate group (G), with 10 rats in each group. The rats in group A were fed with normal diet, and the others were fed with poor iron diet for IDA modeling. The corresponding interventions were given by intragastric administration once a day. The iron ion concentrations of group C, E, F and G were 2.0 mg/kg, and the protein and oligopeptide concentrations of group D, E, F and G were 2 000 mg/kg. Body weight and hemoglobin of rats were measured weekly during 21-day intervention. At the end, peripheral blood samples were collected, and blood routine, iron metabolism and liver function indicators were determined. @*Results@#After the intervention, among blood routine indicators, the rats in group C, E, F and G showed elevated hemoglobin, red blood cell, mean corpuscular volume and hematocrit, and decreased free protoporphyrin and mean corpuscular hemoglobin concentration when compared with the rats in group B (all P<0.05); among iron metabolism indicators, the rats in group C, E and G showed elevated serum ferritin, the rats in group C, E, F and G showed elevated serum iron, the rats in group C, D, E, F and G showed decreased unsaturated iron binding capacity and total iron binding capacity when compared with the rats in group B (all P<0.05); among liver function indicators, the rats in group E and G showed decreased alanine transaminase when compared with the rats in group B (both P<0.05). @*Conclusions@#Lactoprotein alone could not completely improve IDA in rats compared with traditional iron supplement (ferrous sulfate). Lactoprotein iron chelate, especially whey protein oligopeptide iron chelate, could significantly improve IDA, iron reserve and liver function damage in rats.

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