Adding plasmonic diagnostics and also microfluidics

Diabetes mellitus (DM) is one of the major metabolic diseases. Xerostomia and salivary gland dysfunction are of its common oral complications. Exosomes, as a new therapeutic potential containing nucleic acids, proteins and lipids, act as effective vehicles for target molecules delivery. Accordingly, their therapeutic use is gaining much interest. Therefore, this work aimed to assess the therapeutic efficacy of salivary exosomes in ameliorating DM and combating xerostomia as a complication of salivary gland dysfunction in diabetic rats. In the current study, salivary exosomes were injected intravenously to rats of group II (Salivary Exo-treated group) one week after diabetes induction. Group I (Diabetic group) was left untreated. Blood sugar level was checked weekly. Water intake, salivary flow rate, salivary amylase and serum nitric oxide were assessed before and after diabetes induction and at the end of the study. After 5 weeks from the beginning of the study, salivary gland tissues were dissected and examined histologically and ultrastructurally. Gene expression of the inflammatory markers NFκB/p65 and TNFα was assessed by polymerase chain reaction. The results showed that salivary exosomes reduced blood glucose levels and enhanced salivary glands' function. This was indicated by a decrease in water intake, salivary amylase and serum nitric oxide in addition to an increase in salivary flow rate. This was confirmed histologically, ultrastructurally and via downregulation of NFκB/p65 and TNFα gene expression. Our results concluded that salivary exosomes could be considered as a novel cell free based therapy in treatment of xerostomia and salivary gland dysfunction in DM.Small molecule RNA host gene 1 (SNHG1) has been found to be an important regulator in the neurotoxicity of Parkinson's disease (PD). However, the underlying molecular mechanisms of SNHG1 in PD remains elusive. The expression of SNHG1, microRNA (miR)-181a-5p, and C-X-C motif chemokine 12 (CXCL12) mRNA was detected using quantitative real-time polymerase chain reaction. Cell viability and apoptosis were analyzed by cell counting kit-8 and Flow cytometry, respectively. Western blot was utilized to determine the levels of B-cell lymphoma-2 (Bcl-2), CyclinD1, Cleaved-caspase-3, and CXCL12 protein. The interaction between miR-181a-5p and SNHG1 or CXCL12 was confirmed by the dual-luciferase reporter assay. We discovered that SNHG1 was significantly elevated, while miR-181a-5p was decreased in N-methyl-4-phenylpyridinium (MPP+)-treated neuroblastoma cells in dose-dependent manners. MPP+ induced cell viability inhibition and apoptosis promotion, while these effects were reversed by SNHG1 knockdown or miR-181a-5p re-expression. SNHG1 directly bound to miR-181a-5p, and miR-181a-5p inhibition could block the action of SNHG1 knockdown on MPP+-induced neurotoxicity in neuroblastoma cells. CXCL12 was identified as a downstream target of miR-181a-5p, and the impact of miR-181a-5p on MPP+-induced neuronal damage could be attenuated by CXCL12 overexpression. Besides, SNHG1 could indirectly regulate CXCL12 expression via miR-181a-5p. We demonstrated that SNHG1 promoted MPP+ induced neuronal injury in neuroblastoma cells by regulating miR-181a-5p/CXCL12 axis, suggesting SNHG1 might contribute to the development of PD, which provided a novel insight into the pathogenesis and treatment of PD.LDLR-related protein 1B (LRP1B) is believed to internalize ligands through receptor-mediated endocytosis. Previous epigenetic and genetic studies have indicated that impaired LRP1B mRNA expression might be related to gastric carcinogenesis. However, expression and prognostic significance of LRP1B protein remain to be elucidated. This study aimed to unravel the clinicopathological characteristics of LRP1B protein expression in gastric cancer. Immunohistochemical staining with antibodies specific to LRP1B peptide, which has an EXXXLL motif-containing region in the C-terminal flexible loop for intracellular sorting, was performed with 100 gastric cancer tissue specimens. Out of 100 tissue specimens, 45 exhibited cytoplasmic localization of LRP1B immunoreactivity. This cytoplasmic localization of LRP1B was significantly higher (P = 0.044) in intestinal-type gastric cancer (25 of 44) than in diffuse-type gastric cancer (20 of 56). Notably, cytoplasmic LRP1B immunoreactivity was significantly associated with low clinicopathological stage and favorable prognosis of patients with diffuse-type gastric cancer (P = 0.014), but nor with intestinal-type gastric cancer (P = 0.994). Multivalent analysis revealed that cytoplasmic LRP1B immunoreactivity had an independent favorable prognostic value in diffuse-type gastric cancer (P = 0.046; hazard ratio 3.058, 95% confidence interval 1.022-9.149). In contrast, no significant relation of cytoplasmic LRP1B immunoreactivity to patients' prognosis was found in intestinal-type gastric cancer. Double immunocytochemical staining demonstrated that cytoplasmic LRP1B was co-localized with RAB11FIP1, which constituted the endocytic recycling compartments in diffuse-type gastric cancer cells. The findings of this study indicated that impaired endocytosis of the cytoplasmic domain of LRP1B, resulting in insufficient ligand internalization, is related to poor prognosis of patients with diffuse-type gastric cancer.
To more comprehensively evaluate the ability of the parameters reflecting the morphological and biomechanical properties of the cornea to distinguish clinical keratoconus (CKC) and forme fruste keratoconus (FFKC) from normal.
Normal eyes (n = 50), CKC (n = 45) and FFKC (n = 15) were analyzed using Pentacam, Corvis ST and ORA. Stepwise logistic regression of all parameters was performed to obtain the optimal combination model capable of distinguishing CKC, FFKC from normal, named SLR1 and SLR2, respectively. see more Receiver operating characteristic (ROC) curves were applied to determine the predictive accuracy of the parameters and the two combination models, as described by the area under the curve (AUC). AUCs were compared using the DeLong method.
The SLR1 model included only the TBI output by Pentacam, while the SLR2 model included the morphological parameter F.Ele.Th and two parameters from the Corvis ST, HC DfA and SP-A1. The majority of the parameters had sufficient strength to differentiate the CKC from normal corneas, even the seven separate parameters and the SLR1 model had a discrimination efficiency of 100%. The predictive accuracy of the parameters was moderate for FFKC, and the SLR2 model (0.965) presented an excellent AUC, followed by TBI, F.Ele.Th and BAD-D.
The F.Ele.Th from Pentacam was the most sensitive morphological parameter for FFKC, and the combination of F.Ele.Th, HC DfA and SP-A1 made the diagnosis of FFKC more efficient. The CRF and CH output by ORA did not improve the combined diagnosis, despite the corneal combination of morphological and biomechanical properties that optimized the diagnosis of FFKC.
The F.Ele.Th from Pentacam was the most sensitive morphological parameter for FFKC, and the combination of F.Ele.Th, HC DfA and SP-A1 made the diagnosis of FFKC more efficient. The CRF and CH output by ORA did not improve the combined diagnosis, despite the corneal combination of morphological and biomechanical properties that optimized the diagnosis of FFKC.
To evaluate the performance of an AI-based diabetic retinopathy (DR) grading model in real-world community clinical setting.
Participants with diabetes on record in the chosen community were recruited by health care staffs in a primary clinic of Zhengzhou city, China. Retinal images were prospectively collected during December 2018 and April 2019 based on intent-to-screen principle. A pre-validated AI system based on deep learning algorithm was deployed to screen DR graded according to the International Clinical Diabetic Retinopathy scale. Kappa value of DR severity, the sensitivity, specificity of detecting referable DR (RDR) and any DR were generated based on the standard of the majority manual grading decision of a retina specialist panel.
Of the 193 eligible participants, 173 (89.6%) were readable with at least one eye image. Mean [SD] age was 69.3 (9.0) years old. Total of 321 eyes (83.2%) were graded both by AI and the specialist panel. The κ value in eye image grading was 0.715. The sensitivity, onsistency was found between AI and manual grading. These prospective evidences were essential for regulatory approval.
To compare two commercially available staining solutions (MembraneBlue Dual® by D.O.R.C., Netherlands, and TWIN by AL.CHI.MI.A. S.R.L., Italy), in terms of intraoperative handling, staining efficacy and safety, in eyes undergoing surgery for idiopathic epiretinal membrane (ERM).
In this observational cross-sectional study, the performance of the dyes used during the procedure (cohesion, ERM and internal limiting membrane [ILM] staining efficacy) was scored by the surgeon using a customized questionnaire after 10 procedures with each of the two dyes. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), blue-light fundus autofluorescence (BAF), and microperimetry-determined retinal sensitivity were reviewed preoperatively and then at 1 and 3months after surgery.
ILM staining efficacy with TWIN was scored 2.89 ± 0.33 by the surgeons, which turned out to be higher than with MembraneBlue Dual® (1.90 ± 0.31, P = 0.0002). The cohesion score was 2.70 ± 0.48 for TWIN and resulted significantly higher than with MembraneBlue Dual® (1.60 ± 0.51, P = 0.0010). BCVA, CFT and retinal sensitivity were similar in the two groups, 1 and 3months postoperatively (P nonsignificant for all).
Both TWIN and MembraneBlue Dual® dyes showed suitable staining properties and equivalent safety and efficacy profiles, both intra- and postoperatively. The TWIN dye might offer a solution for surgeons who prefer a more cohesive and stable dye.
Both TWIN and MembraneBlue Dual® dyes showed suitable staining properties and equivalent safety and efficacy profiles, both intra- and postoperatively. The TWIN dye might offer a solution for surgeons who prefer a more cohesive and stable dye.
The aim of this study was to employ newly developed advanced image analysis software to evaluate changes in retinal layer thickness following hemodialysis.
A non-randomized prospective study of patients with end-stage renal disease assessed on the same day before and after hemodialysis. Intraocular pressure and central corneal thickness were analyzed, and spectral domain optical coherence tomography results were automatically segmented using the Orion software and then compared. All patients had normal retinal optical coherence tomography findings before hemodialysis.
Of the 31 suitable end-stage renal disease patients treated with hemodialysis who provided consent to participate, seven were unable to complete all evaluations, leaving 24 patients for analysis in the final study group. Their mean age was 66.67±14.3 years (range 35-88), and 62.5% were males. Mean central corneal thickness did not change following hemodialysis (563.4±30.2 µm to 553.1±47.2 µm, p=.247), while mean intraocular pressure decreased (14.