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1.
BMC Ophthalmol ; 23(1): 146, 2023 Apr 07.
Article in English | MEDLINE | ID: mdl-37029355

ABSTRACT

BACKGROUND: Premacular hemorrhage is among the causes of sudden deterioration of visual acuity. This study aimed to investigate the therapeutic outcomes of a new Q-switched Nd:YAG laser on premacular hemorrhage. METHODS: Retrospective, case series study of 16 eyes from 16 patients diagnosed with premacular hemorrhage, including 3 cases of Valsalva retinopathy, 8 cases of retinal macroaneurysm, 3 cases of diabetic retinopathy, 1 case of trauma-related hemorrhage and 1 case with leukemia. A 1064nm Q-switched Nd:YAG laser was performed to puncture the posterior hyaloid and inner limiting membrane to drain the hemorrhage. RESULTS: The success rate of 16 patients with premacular hemorrhage drainage was 100% in this study. Improved visual acuity was observed in each patient. CONCLUSIONS: In this case series of 16 patients, the new Q-switched Nd:YAG laser was successful in draining premacular hemorrhage with no serious complications.


Subject(s)
Laser Therapy , Lasers, Solid-State , Humans , Treatment Outcome , Lasers, Solid-State/therapeutic use , Retrospective Studies , Laser Therapy/adverse effects , Retinal Hemorrhage/diagnosis , Retinal Hemorrhage/etiology , Retinal Hemorrhage/surgery , Vitreous Body
2.
J Clin Lab Anal ; 36(10): e24684, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36045593

ABSTRACT

BACKGROUND: Cell division cycle 42 (CDC42) modulates the pathogenesis of allergic rhinitis (AR) through regulating immunity, allergic response, and T-helper (Th)1/Th2 imbalance. This study aimed to evaluate the potential of CDC42 to reflect disease risk, symptom scores, and Th1/Th2 axis of AR and the correlation of its vertical change with symptom amelioration after treatment. METHODS: CDC42, Th1 cells, and Th2 cells in the peripheral blood mononuclear cells (PBMCs) and interferon-γ and interleukin-4 in the serum were determined in 200 AR patients. Simultaneously, PBMC CDC42 was detected in 50 non-atopic obstructive snoring patients [as disease controls (DCs)] and 50 healthy controls (HCs). RESULTS: CDC42 was increased in AR patients compared with DCs and HCs (both p < 0.001) but showed no difference between DCs and HCs (p = 0.054). In AR patients, CDC42 was positively linked to rhinorrhea, itching, sneezing, and total nasal symptom scores (TNSS) (all p < 0.05), but not congestion score (p = 0.052). Meanwhile, CDC42 showed positive correlations with Th2 cells (p < 0.001) and interleukin-4 (p = 0.005), a negative correlation with Th1/Th2 axis (p = 0.001), but no correlation with Th1 cells (p = 0.095) or interferon-γ (p = 0.174). Notably, CDC42 at week 4 after treatment (W4) was reduced compared with that at enrollment (W0) (p < 0.001) and positively correlated with TNSS at W4 (p < 0.001); from W0 to W4, CDC42 change also positively correlated with TNSS change (p = 0.004). CONCLUSION: CDC42 is elevated and positively correlates with symptom scores and Th2 cells, whose short-term reduction reflects symptom alleviation in AR patients.


Subject(s)
Interleukin-4 , Rhinitis, Allergic , Cell Cycle , Cytokines/metabolism , Humans , Interferon-gamma/metabolism , Interleukin-4/metabolism , Leukocytes, Mononuclear/metabolism , Rhinitis, Allergic/epidemiology , Th2 Cells/metabolism , Th2 Cells/pathology , cdc42 GTP-Binding Protein
3.
BMC Ophthalmol ; 21(1): 49, 2021 Jan 19.
Article in English | MEDLINE | ID: mdl-33468097

ABSTRACT

BACKGROUND: Tears in Schwartz-Matsuo syndrome are generally confirmed by preoperative ophthalmoscopic examination. A case of Schwartz-Matsuo syndrome with a tear detected by ultrasound biomicroscopy (UBM) and treated by UBM-guided scleral buckling was reported, and its mechanism was analysed. CASE PRESENTATION: A 40-year-old Chinese man presented with blurry vision and intermittent eye pain in his left eye for three days. The visual acuity of the left eye decreased from 20/20 to 20/40, and the intraocular pressure (IOP) fluctuated dramatically from 24.0 mmHg to 56.7 mmHg at the first visit. Gonioscopy revealed that the chamber angle remained open. A macula-involving inferior retinal detachment extending from 4:30 to 9:30 with no obvious causative break was observed through ophthalmoscopic examination. However, a single small tear was detected at the nonpigmented epithelium of pars plana of the ciliary body at approximately 7-8 o'clock by UBM. The loss of photoreceptor outer segments and ellipsoid zone and the existence of macular microcysts in the inner and outer nuclear layers were observed in the detached macula by optical coherence tomography. Then, he underwent successful scleral buckling guided by UBM. Three months later, the retina was flat with normal IOP, and the best corrected visual acuity of his left eye gradually improved to 20/25. UBM confirmed the closure of the tear. CONCLUSIONS: Tear of the nonpigmented epithelium of the ciliary body is a rare condition associated with Schwartz-Matsuo syndrome. UBM plays a key role in detecting occult tears of the nonpigmented epithelium of the ciliary body, guiding scleral buckling surgery, and observing the closure of the tear postoperatively.


Subject(s)
Retinal Detachment , Scleral Buckling , Adult , Ciliary Body/diagnostic imaging , Ciliary Body/surgery , Epithelium , Humans , Male , Microscopy, Acoustic , Retinal Detachment/diagnosis , Retinal Detachment/etiology , Retinal Detachment/surgery
4.
BMC Ophthalmol ; 21(1): 161, 2021 Apr 05.
Article in English | MEDLINE | ID: mdl-33820544

ABSTRACT

BACKGROUND: To compare changes in retinal microvasculature of young and elderly patients with retinal vein occlusion (RVO) after anti-VEGF treatment. METHODS: RVO patients who underwent anti-VEGF treatment were retrospectively reviewed and categorized into two groups based on age. The OCT angiography images were obtained during each visit. Best corrected visual acuity (BCVA), vessel density (VD) and foveal avascular zone (FAZ) were measured and compared between the two groups. Vision improvements and retinal microvasculature changes were also correlated. RESULTS: Twenty patients with 20 eyes were enrolled in the younger group and 46 patients with 46 eyes were enrolled in the older group. Younger patients demonstrated better BCVA, higher VD and smaller FAZ than older patients at 12 months after the first anti-VEGF treatment. The improvement of VD was observed only in the younger group. A positive correlation between vision improvement and VD increase was noted. CONCLUSIONS: Young patients with RVO can achieve rapid rehabilitation of deep retinal vasculature which lead to a better visual outcome.


Subject(s)
Retinal Vein Occlusion , Aged , Fluorescein Angiography , Humans , Retinal Vein Occlusion/drug therapy , Retinal Vessels/diagnostic imaging , Retrospective Studies , Tomography, Optical Coherence , Visual Acuity
5.
BMC Ophthalmol ; 19(1): 17, 2019 Jan 14.
Article in English | MEDLINE | ID: mdl-30642294

ABSTRACT

BACKGROUND: To identify the clinical characteristics, prognostic factors and visual outcomes in posterior segment IOFBs patients managed by PPV in a tertiary hospital. METHODS: A retrospective chart review was performed for 56 patients, who had PPV for IOFBs removal between November 2013 and November 2015. The mechanisms of injury, the nature of the IOFBs, the BCVA before and after the surgery, the penetrating site and the complications of the surgery were all collected. Univariate analyses were conducted to evaluate the prognostic factors. RESULTS: The mean age of the patients was 36.4 years. The nature of IOFBs was mainly metal. Most injuries were commonly caused by hammering the metal. The mean preoperative VA was 2.30 logMAR, and mean final VA was 0.92 logMAR. From univariate analysis, good visual outcome was correlated with the good visual acuity before surgery and poor visual outcome was correlated with the macular break and multiple surgeries. CONCLUSIONS: In a tertiary hospital of eastern China, most cases of IOFBs were work-related. The prognosis of the patients was really well in the patients with good presenting visual acuity. Nevertheless the prognosis was not good for those patients who had macular injury or underwent several surgeries because of retinal detachment, epiretinal membrane or proliferative vitreous retinopathy. Good facilities for eye protection are urgently in demand for the workers indeed.


Subject(s)
Eye Foreign Bodies/surgery , Ophthalmologic Surgical Procedures , Posterior Eye Segment/surgery , Adult , Aged , Eye Foreign Bodies/etiology , Eye Foreign Bodies/physiopathology , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Visual Acuity/physiology , Vitrectomy/methods
6.
BMC Ophthalmol ; 19(1): 94, 2019 Apr 24.
Article in English | MEDLINE | ID: mdl-31014258

ABSTRACT

BACKGROUND: The exact pathogenesis of idiopathic choroidal neovascularization (ICNV) remains unclear. Cytokine-mediated inflammation has been thought to be involved in the pathophysiology of ICNV. The purpose of this study was to investigate serum cytokine profiles in patients with ICNV and to explore the relationship between serum cytokine levels and ICNV severity. METHODS: This case-control study was conducted in 32 ICNV patients and 30 healthy volunteers. Clinical and demographic information was obtained from the medical data platform and the serum was analysed with a multiplex assay to determine the levels of seven cytokines: interleukin (IL)-2, IL-10, IL-15, IL-17, basic fibroblast growth factor (basic FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF). RESULTS: Serum levels of IL-2, IL-10, IL-17, basic FGF, and VEGF were elevated in ICNV patients compared to controls. Serum GM-CSF levels were positively related to central retinal thickness, and serum IL-17 levels were positively related to CNV lesion area. CONCLUSION: Serum inflammatory cytokines were significantly elevated in ICNV patients compared to controls. This suggests that systemic inflammation may play a critical role in the physiopathology of ICNV.


Subject(s)
Choroidal Neovascularization/blood , Cytokines/blood , Adult , Biomarkers/blood , Case-Control Studies , Choroidal Neovascularization/physiopathology , Female , Humans , Inflammation/physiopathology , Male , Middle Aged , Retina/pathology , Visual Acuity/physiology
8.
Apoptosis ; 21(1): 96-109, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26481477

ABSTRACT

Heat shock proteins (HSPs) were originally identified as stress-responsive proteins and serve as molecular chaperones in different intracellular compartments. Translocation of HSPs to the cell surface and release of HSPs into the extracellular space have been observed during the apoptotic process and in response to a variety of cellular stress. Here, we report that UV irradiation and cisplatin treatment rapidly induce the expression of membrane-bound Hsp60, Hsp70, and Hsp90 upstream the phosphatidylserine exposure. Membrane-bound Hsp60, Hsp70 and Hsp90 could promote the release of IL-6 and IL-1ß as well as DC maturation by the evaluation of CD80 and CD86 expression. On the other hand, Hsp60, Hsp70 and Hsp90 on cells could facilitate the uptake of dying cells by bone marrow-derived dendritic cells. Lectin-like oxidized LDL receptor-1 (LOX-1), as a common receptor for Hsp60, Hsp70, and Hsp90, is response for their recognition and mediates the uptake of dying cells. Furthermore, membrane-bound Hsp60, Hsp70 and Hsp90 could promote the cross-presentation of OVA antigen from E.G7 cells and inhibition of the uptake of dying cells by LOX-1 decreases the cross-presentation of cellular antigen. Therefore, the rapid exposure of HSPs on dying cells at the early stage allows for the recognition by and confers an activation signal to the immune system.


Subject(s)
Chaperonin 60/genetics , Cross-Priming , Dendritic Cells/immunology , HSP70 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/genetics , Mitochondrial Proteins/genetics , Animals , Apoptosis/drug effects , B7-1 Antigen/genetics , B7-1 Antigen/immunology , B7-2 Antigen/genetics , B7-2 Antigen/immunology , CHO Cells , Cell Membrane/drug effects , Cell Membrane/immunology , Cell Membrane/metabolism , Chaperonin 60/immunology , Cricetulus , Dendritic Cells/cytology , Dendritic Cells/drug effects , Gene Expression Regulation , HL-60 Cells , HSP70 Heat-Shock Proteins/immunology , HSP90 Heat-Shock Proteins/immunology , Humans , Interleukin-1beta/genetics , Interleukin-1beta/immunology , Interleukin-6/genetics , Interleukin-6/immunology , Mice , Mice, Inbred C57BL , Mitochondrial Proteins/immunology , Ovalbumin/pharmacology , Phosphatidylserines/immunology , Phosphatidylserines/metabolism , Protein Binding , Scavenger Receptors, Class E/genetics , Scavenger Receptors, Class E/immunology , Signal Transduction
9.
Proc Natl Acad Sci U S A ; 108(6): 2623-8, 2011 Feb 08.
Article in English | MEDLINE | ID: mdl-21262818

ABSTRACT

Site-specific and rare cutting nucleases are valuable tools for genome engineering. The generation of double-strand DNA breaks (DSBs) promotes homologous recombination in eukaryotes and can facilitate gene targeting, additions, deletions, and inactivation. Zinc finger nucleases have been used to generate DSBs and subsequently, for genome editing but with low efficiency and reproducibility. The transcription activator-like family of type III effectors (TALEs) contains a central domain of tandem repeats that could be engineered to bind specific DNA targets. Here, we report the generation of a Hax3-based hybrid TALE nuclease with a user-selected DNA binding specificity. We show that the engineered TALE nuclease can bind to its target sequence in vitro and that the homodimeric TALE nuclease can cleave double-stranded DNA in vitro if the DNA binding sites have the proper spacing and orientation. Transient expression assays in tobacco leaves suggest that the hybrid nuclease creates DSB in its target sequence, which is subsequently repaired by nonhomologous end-joining repair. Taken together, our data show the feasibility of engineering TALE-based hybrid nucleases capable of generating site-specific DSBs and the great potential for site-specific genome modification in plants and eukaryotes in general.


Subject(s)
DNA Breaks, Double-Stranded , DNA/chemistry , Deoxyribonucleases/chemistry , Recombinant Fusion Proteins/chemistry , Trans-Activators/chemistry , Deoxyribonucleases/genetics , Protein Engineering/methods , Recombinant Fusion Proteins/genetics , Substrate Specificity , Trans-Activators/genetics
10.
Ophthalmic Genet ; 45(2): 153-158, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38419580

ABSTRACT

BACKGROUND: ATF6-associated Achromatopsia (ACHM) is a rare autosomal recessive disorder characterized by reduction of visual acuity, photophobia, nystagmus, and poor color vision. METHODS: Detailed ophthalmological examinations were performed in a Chinese patient with ACHM. Whole exome sequencing and Sanger sequencing were performed to detect the disease-causing gene in the patient. RESULTS: A 6-year-old girl presented photophobia, low vision and reduced color discrimination. Small yellow lesion in the macula of both eyes was observed. FAF demonstrated hypofluorescence in the macular fovea. OCT images revealed interruption of ellipsoid and interdigitation zone in the foveal area and a loss of the foveal pit. ERG showed relatively normal rod responses and unrecordable cone responses. Sequencing result identified a novel splicing variant c.354 + 6T>C in the ATF6 gene (NM_007348.4). CONCLUSIONS: We reported detailed clinical features and genetic analysis of a new Chinese ATF6-associated patient with ACHM.


Subject(s)
Color Vision Defects , Child , Female , Humans , Activating Transcription Factor 6/genetics , China , Color Vision Defects/diagnosis , Photophobia/diagnosis , Photophobia/pathology , Retinal Cone Photoreceptor Cells/pathology , Tomography, Optical Coherence/methods
11.
Stem Cell Rev Rep ; 19(8): 2929-2942, 2023 11.
Article in English | MEDLINE | ID: mdl-37707669

ABSTRACT

Cell-based therapies have shown great potential because of their abilities to replace dying retinal neuron cells and preserve vision. The migration, proliferation and differentiation of retinal progenitor cells(RPCs) plays a vital role in the integration of the RPCs into the retina when transplanted into the host. Our study aimed to explore the effects of Hyaluronan(HA)-CD44 interactions on the regulation of RPCs migration, proliferation and differentiation, and investigate the underlying regulatory mechanisms. We found that CD44 was expressed in RPCs, and the HA-CD44 interaction markedly improved RPCs adhesion and migration. The stimulation of microRNA-21(miR-21) expression by the HA-CD44 interaction was protein kinase C (PKC)/Nanog-dependent in RPCs. Treatment of RPCs with PKC- or Nanog-specific ASODN or miR-21 antagomir effectively blocked HA-mediated RPCs adhesion and migration. Moreover, Rho-Kinase(ROK)/ Grb2-associated binders(Gab-1) associated phosphatidylinositol 3-kinase(PI3K)/AKT signalling activation was required for HA-CD44 interaction mediated RPCs proliferation and neuronal differentiation. Our findings demonstrated new roles for the HA-CD44 interaction in regulating the migration, proliferation and neuronal differentiation of RPCs. HA-CD44 signalling could represent a novel approach to controlling RPC fates, and the findings may be instructive for the application of RPCs for future therapeutic applications.


Subject(s)
Hyaluronic Acid , MicroRNAs , Animals , Mice , Hyaluronic Acid/pharmacology , Phosphatidylinositol 3-Kinases , Retina , Cell Differentiation , Stem Cells , Cell Proliferation , MicroRNAs/genetics
12.
Am J Ophthalmol Case Rep ; 32: 101907, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37560557

ABSTRACT

Purpose: To report 2 polypoidal choroidal vasculopathy (PCV) patients whose massive hemorrhagic pigment epithelial detachments (PEDs) were flattened within a short period after surgery. Observations: Two PCV patients who presented with submacular hemorrhage and massive hemorrhagic PEDs with sizes of more than 50 disc areas underwent pars plana vitrectomy combined with subretinal injection of tissue plasminogen activator (tPA), intravitreous injection of anti-vascular endothelial growth factor medicine, and perfluoropropane tamponade. The massive hemorrhagic PEDs were flattened within a short period after both surgeries, and both patients experienced improved visual acuity. Conclusions: These findings suggest that subretinal injection of tPA together with perfluoropropane tamponade promotes the rapid clearance of hemorrhage under RPE.

13.
Ocul Immunol Inflamm ; : 1-12, 2023 Apr 06.
Article in English | MEDLINE | ID: mdl-37023410

ABSTRACT

PURPOSE: Diabetic retinopathy (DR) has become a major cause of blindness with increased prevalence of diabetic mellitus. Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) plays a part in pathological neovascularization. This study aimed to investigate the role of CEACAM1 in the progression of DR. METHODS: Aqueous and vitreous samples were collected from proliferative or non-proliferative DR and the control group. Multiplex fluorescent bead-based immunoassays were used to detect the levels of Cytokines. Expression of CEACAM1, VEGF, VEGF receptor 2 (VEGFR2) and hypoxia-induced factor-1α (HIF-1α) were detected in human retinal microvascular endothelial cells (HRECs). RESULTS: CEACAM1 and VEGF levels were significantly upregulated in PDR group and positively correlated with PDR progression. Expression CEACAM1 and VEGFR2 were increased in HRECs under hypoxic conditions. The HIF-1α/VEGFA/VEGFR2 pathway was blocked by CEACAM1 siRNA in vitro. CONCLUSIONS: CEACAM1 might play a role in the pathology of PDR. CEACAM1 might be a therapeutic target for retinal neovasculariztion.

14.
Adv Ophthalmol Pract Res ; 3(2): 67-79, 2023.
Article in English | MEDLINE | ID: mdl-37846376

ABSTRACT

Background: The fast development of swept-source optical coherence tomography (SS-OCT) and swept-source optical coherence tomography angiography (SS-OCTA) enables both anterior and posterior imaging of the eye. These techniques have evolved from a research tool to an essential clinical imaging modality. Main text: The longer wavelength and faster speed of SS-OCT and SS-OCTA facilitate better visualization of structure and vasculature below pigmented tissue with a larger field of view of the posterior segment and 360-degree visualization of the anterior segment. In the past 10 years, algorithms dealing with OCT and OCTA data also vastly improved the image quality and enabled the automated quantification of OCT- and OCTA-derived metrics. This technology has enriched our current understanding of healthy and diseased eyes. Even though the high cost of the systems currently limited the widespread use of SS-OCT and SS-OCTA at the first beginning, the gap between research and clinic practice got obviously shortened in the past few years. Conclusions: SS-OCT and SS-OCTA will continue to evolve rapidly, contributing to a paradigm shift toward more widespread adoption of new imaging technology in clinical practice.

15.
Plant Mol Biol ; 78(3): 311-21, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22167390

ABSTRACT

Transcriptional activator-like effectors (TALEs) are proteins secreted by Xanthomonas bacteria when they infect plants. TALEs contain a modular DNA binding domain that can be easily engineered to bind any sequence of interest, and have been used to provide user-selected DNA-binding modules to generate chimeric nucleases and transcriptional activators in mammalian cells and plants. Here we report the use of TALEs to generate chimeric sequence-specific transcriptional repressors. The dHax3 TALE was used as a scaffold to provide a DNA-binding module fused to the EAR-repression domain (SRDX) to generate a chimeric repressor that targets the RD29A promoter. The dHax3.SRDX protein efficiently repressed the transcription of the RD29A::LUC transgene and endogenous RD29A gene in Arabidopsis. Genome wide expression profiling showed that the chimeric repressor also inhibited the expression of several other genes that contain the designer TALE-target sequence in their promoters. Our data suggest that TALEs can be used to generate chimeric repressors to specifically repress the transcription of genes of interest in plants. This sequence-specific transcriptional repression by direct on promoter effector technology is a powerful tool for functional genomics studies and biotechnological applications.


Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/genetics , Repressor Proteins/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Base Sequence , DNA, Plant/genetics , Genes, Plant , Molecular Sequence Data , Plants, Genetically Modified , Promoter Regions, Genetic , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Repressor Proteins/metabolism
16.
Plant Mol Biol ; 78(4-5): 407-16, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22271303

ABSTRACT

Transcription activator-like effectors (TALEs) can be used as DNA-targeting modules by engineering their repeat domains to dictate user-selected sequence specificity. TALEs have been shown to function as site-specific transcriptional activators in a variety of cell types and organisms. TALE nucleases (TALENs), generated by fusing the FokI cleavage domain to TALE, have been used to create genomic double-strand breaks. The identity of the TALE repeat variable di-residues, their number, and their order dictate the DNA sequence specificity. Because TALE repeats are nearly identical, their assembly by cloning or even by synthesis is challenging and time consuming. Here, we report the development and use of a rapid and straightforward approach for the construction of designer TALE (dTALE) activators and nucleases with user-selected DNA target specificity. Using our plasmid set of 100 repeat modules, researchers can assemble repeat domains for any 14-nucleotide target sequence in one sequential restriction-ligation cloning step and in only 24 h. We generated several custom dTALEs and dTALENs with new target sequence specificities and validated their function by transient expression in tobacco leaves and in vitro DNA cleavage assays, respectively. Moreover, we developed a web tool, called idTALE, to facilitate the design of dTALENs and the identification of their genomic targets and potential off-targets in the genomes of several model species. Our dTALE repeat assembly approach along with the web tool idTALE will expedite genome-engineering applications in a variety of cell types and organisms including plants.


Subject(s)
Protein Engineering/methods , Trans-Activators/genetics , DNA Breaks, Double-Stranded , DNA Cleavage , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Deoxyribonucleases, Type II Site-Specific , Endonucleases/genetics , Endonucleases/metabolism , Homeodomain Proteins/genetics , Plant Leaves/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Repetitive Sequences, Nucleic Acid , Reproducibility of Results , Nicotiana/genetics
17.
Inflamm Res ; 61(11): 1257-63, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22820943

ABSTRACT

OBJECTIVE AND DESIGN: To determine whether the neurokinin-1 receptor (NK1R) plays a role in the activation of RBL-2H3 mast cells after FcεRΙ aggregation. MATERIALS AND METHODS: NK1R expression in RBL-2H3 cells was inhibited by small hairpin RNA (shRNA) against NK1R, and determined by western blotting. For activation, both NK1R knockdown and control RBL-2H3 cells were sensitized by dinitrophenol (DNP)-specific IgE and stimulated with the antigen DNP-bovine serum albumin (BSA). Following the activation of RBL-2H3 cells, monocyte chemoattractant protein (MCP-1) production and intracellular calcium flux were monitored by ELISA and confocal microscopy assay, respectively. For investigation of the signaling mechanism, phosphorylation of mitogen-activated protein kinases (MAPKs) after RBL-2H3 cell activation was assessed by western blotting. RESULTS: shRNA-NK1R mediated an effective inhibition of NK1R expression in RBL-2H3 cells. Protein production of MCP-1 was reduced by more than 55 % in NK1R knockdown RBL-2H3 cells compared with control RBL-2H3 cells. In addition, both calcium mobilization and phosphorylation levels of MAPKs (Erk1/2, JNK, and p38) after DNP-BSA stimulation (via FcεRΙ) were decreased due to the inhibition of NK1R expression. CONCLUSION: NK1R is required for the activation of RBL-2H3 cells following FcεRΙ engagement and involved in the regulation of MAPK signaling pathways.


Subject(s)
Mast Cells/metabolism , Mitogen-Activated Protein Kinases/metabolism , Receptors, IgE/metabolism , Receptors, Neurokinin-1/metabolism , Animals , Calcium/metabolism , Cell Line, Tumor , Chemokine CCL2/metabolism , Gene Knockdown Techniques , RNA, Small Interfering/genetics , Rats , Receptors, Neurokinin-1/genetics
18.
Curr Oncol ; 29(2): 490-496, 2022 01 24.
Article in English | MEDLINE | ID: mdl-35200544

ABSTRACT

Cytomegalovirus (CMV) retinitis is a rare end-organ disease of CMV infection and is a marker of severe immunosuppression, especially in human immunodeficiency virus (HIV)-positive patients. In multiple myeloma (MM) patients, CMV retinitis has been reported in the post-transplant setting, with an incidence lower than 0.2%, and in patients receiving lenalidomide. Here, we describe the first case of CMV retinitis in myeloma patients following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T (BCMA CAR-T) cell therapy. In addition to CMV, the patient developed multiple infections including a mouth ulcer, pneumonia, and fungal enteritis. While the complete remission (CR) status of MM was maintained, he regained a visual acuity of 20/1000 after appropriate ophthalmologic treatment. This single case illustrates the potential of BCMA CAR-T therapy to induce profound humoral immunosuppression, and demonstrates an imperative need for an established standard of monitoring and prophylaxis of post-CAR-T infections.


Subject(s)
Cytomegalovirus Retinitis , Multiple Myeloma , Receptors, Chimeric Antigen , Retinal Detachment , B-Cell Maturation Antigen/therapeutic use , Cell- and Tissue-Based Therapy , Cytomegalovirus Retinitis/etiology , Humans , Male , Multiple Myeloma/drug therapy , Receptors, Chimeric Antigen/therapeutic use
19.
Front Nutr ; 9: 890277, 2022.
Article in English | MEDLINE | ID: mdl-35669071

ABSTRACT

The essential fatty acids (EFA), n3 alpha-linolenic acid (ALA), and n6 linoleic acid (LA) are of benefit in diabetes mellitus, but their mechanisms of action are unknown. We, therefore, examined the effects of EFAs on the metabolism, gut microbiota, and inflammatory and retinal histopathology indices in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) animals, and we assessed the levels of vitreal lipoxin A4 (LXA4)-derived from LA-in subjects with diabetic retinopathy (DR). STZ-induced T1DM rats received LA or ALA 100 µg/day intraperitoneally on alternate days for 21 days, and their blood glucose; lipid profile; plasma, hepatic, and retinal fatty acid profiles (by gas chromatography); retinal histology; activities of hepatic and retinal desaturases; and inflammatory markers (by qRT-PCR) were evaluated. Gut microbiota composition was assayed by 16S rDNA sequencing technology of the fecal samples, and their short-chain fatty acids and bile acids were assayed by gas chromatography, liquid chromatography coupled with tandem mass spectrometry, respectively. The human vitreal fatty acid profiles of subjects with proliferative DR and LXA4 levels were measured. LA and ALA significantly improved the plasma glucose and lipid levels; increased the abundance of Ruminococcaceae (the ALA-treated group), Alloprevotella, Prevotellaceae_Ga6A1_group, Ruminococcaceae_UCG_010, and Ruminococcus_1 (the LA-treated group) bacteria; enhanced acetate and butyrate levels; and augmented fecal and hepatic concentrations of cholic acid, chenodeoxycholic acid, and tauro ursodeoxycholic acid in ALA- and LA-treated animals. Significant STZ-induced decreases in plasma LA, gamma-linolenic acid, arachidonic acid, and ALA levels reverted to near normal, following LA and ALA treatments. Significant changes in the expression of desaturases; COX-2, 5-LOX, and 12-LOX enzymes; and cytokines in T1DM were reverted to near normal by EFAs. DR subjects also had low retinal LXA4 levels. The results of the present study show that ALA and LA are of significant benefit in reversing metabolism, gut microbiota, and inflammatory and retinal index changes seen in T1DM, suggesting that EFAs are of benefit in diabetes mellitus.

20.
Front Plant Sci ; 13: 806765, 2022.
Article in English | MEDLINE | ID: mdl-35154223

ABSTRACT

KNOTTED1-like homeobox (KNOX) transcription factors (TFs) belonging to the homeobox TF family play important roles in plant growth, development, and responses to abiotic and biotic stress. However, little information is available on KNOX TF in pear (Pyrus). In this study, 19 PbKNOXs TFs were re-identified in pear (Pyrus bretschneideri Rehd.). Phylogenetic analysis revealed that the TFs were clustered into three groups with 10 conserved motifs, some of which were group- or subgroup-specific, implying that they are important for the functions of the KNOX in these clades. PbKNM1 and PbKNM2 are KNM (encodes a MEINOX domain but not a homeodomain) genes identified in pear for the first time. KNOX genes in Pyrus and Malus were closely related, and a collinear relationship among PbKNOX genes in Pyrus and Malus was observed. Analysis of the expression patterns of PbKNOX genes in different tissues, at various growth stages, and in response to abiotic and biotic stress revealed that PbKNOXs are involved in plant growth and development. Our comparative transcriptional analysis of dwarf mutant varieties revealed that genes belonging to class I are highly expressed compared with genes in other classes. Analysis of the expression of PbKNOX genes in the hybrid offspring of vigorous and dwarf varieties revealed that PbKNOX genes were highly expressed in the vigorous offspring and weakly expressed in the dwarf offspring. These findings provide new insight into the function of KNOX TFs in pear and will aid future studies of dwarf fruit trees.

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