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Diabetes detection is pivotal in disease management and complication prevention. Traditional screening methods, like blood tests, are invasive and time-consuming. Deep learning has emerged as a non-invasive and automated alternative for diabetes detection. Convolutional neural networks (CNNs) excel in image analysis tasks, making them ideal for this purpose. This paper employs a CNN-based method for diabetes prediction using retinal images, utilizing the DenseNet169 architecture for feature extraction and diabetic retinopathy (DR) prediction. The APTOS 2019 blindness detection dataset from Kaggle, containing around 13,000 retinal images, is used for training. Pre-processing and normalization precede feature extraction, followed by the prediction of the DR stage. The model aims to classify retinal images into five stages of DR (0 to 4), ranging from no DR to proliferative DR. Our model achieved over 82% accuracy, outperforming advanced algorithms. Model evaluation includes accuracy, precision, recall, and F1 score measures. [ABSTRACT FROM AUTHOR]

PurposeTo compare baseline levels of exploratory biomarkers in the vitreous fluid of patients with primary retinal detachment who subsequently develop proliferative vitreoretinopathy (PVR) versus those who do not.MethodsIn this exploratory case-control study, we evaluated the baseline protein biomarker levels from a biobank containing the vitreous fluid of patients who had undergone primary pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment. Undiluted samples were collected at the time of PPV and stored at -80°C. Samples from 13 patients who developed PVR within 6 months (PVR group) and 13 age- and gender-matched controls who did not develop PVR (control group) were included. Protein abundance levels were evaluated using a proximity extension assay, and a confirmatory enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of vimentin.ResultsBaseline vimentin (Normalized Protein eXpression [NPX], 8.6 vs. 6.4, P < 0.0001) and heme oxygenase 1 (NPX 8.9 vs. 7.0, P < 0.001) levels were found to be elevated in vitreous fluid of patients who subsequently developed PVR compared to those who did not. Confirmatory analysis using ELISA demonstrated mean vimentin concentrations of 7254 vs. 2727 ng/mL in the PVR versus control groups (P = 0.0152). The odds ratio for developing PVR was 14 (confidence interval, 1.4-168; P = 0.03), assuming a baseline vimentin threshold of 7500 ng/mL.ConclusionsVimentin is an intermediate filament protein expressed by retinal glial cells, and our data combined with prior evidence suggest that it may serve as an early vitreous biomarker for subsequent PVR formation and reactive gliosis. Furthermore, we found, for the first time, elevated baseline levels of heme oxygenase 1, a measurable indicator of oxidative stress.Translational relevanceOur positive findings could impact clinical care for retinal detachment patients by facilitating risk stratification for targeted interventions or closer monitoring in those at the highest risk of developing PVR.

Brenner tumors are rare ovarian neoplasms that are typically small and unilateral. Most cases are benign; less than 5% of all Brenner tumors are borderline or proliferative. Brenner tumors originate from the follicular epithelium and consist of ovarian transitional cells surrounded by fibrous tissue. Here we present a case of a 49‐year‐old premenopausal woman from Northern Tanzania. This patient presented to our facility with acute abdominal pain. She also reported abdominal distention which was first noticed 12 months prior to presentation. Magnetic resonance imaging (MRI) identified a 21 × 17 × 5 cm complex cyst with a thickened wall on the right ovary. The radiological findings were suggestive of an ovarian cystadenoma; multiple intramural and subserosal uterine leiomyomas were also noted. A total abdominal hysterectomy (TAH) and bilateral salpingo‐oophorectomy (BSO) was performed. Histopathological findings identified an atypical proliferative borderline Brenner tumor of the right ovary. Postoperative recovery was uneventful, the patient was discharged and managed conservatively postoperatively. [ABSTRACT FROM AUTHOR]

Measuring the ferritin content in the blood is the most informative test for detecting iron deficiency and is recommended by the protocols for the diagnosis of anemia. However, ferritin as a marker of acute and chronic inflammation is nonspecifically increased in various inflammatory conditions. Mechanisms reflecting the significant role of chronic low-intensity inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) are being actively studied. Our aim was to analyze the content of ferritin in the plasma of patients with different stages of diabetic retinopathy (DR) on the background of T2DM in comparison with hemogram indicators and inflammatory markers. Ferritin content in blood plasma was determined by enzyme immunoassay in 106 patients with non-proliferative DR, moderate and progressive proliferative DR. The patients showed an increase in ferritin content relative to the control group and a progressive increase with deepening of the stage of retinopathy. In the group of moderate proliferative DR, the indicator was higher than the control by 23%, and in the group of progressive proliferative DR by 26%. The difference in ferritin content was observed in patients depending on gender. In men, an increase in ferritin content was found by 1.6 times relative to the value in women, in groups of proliferative DR, the indicators differed by 1.1 and 1.3 times. Indicators of the number of erythrocytes and hemoglobin content in the blood of male patients had a tendency to decrease compared to similar indicators of healthy men. In patients with T2DM, the ferritin content was elevated regardless of the underlying anemic state, therefore, it cannot be used as a diagnostic test for iron deficiency. A significant two-way correlation of ferritin and interleukin-10 content was found (r = 0.235). No correlation was found with the index of interleukin-1b and non-neuronal enolase, which characterizes the content of ferritin in the blood of patients with DR on the background of T2DM as a marker of chronic inflammation. [ABSTRACT FROM AUTHOR]

Background: Endometrial disorders are among the most common gynecological conditions globally. Abnormal uterine bleeding (AUB) refers to any irregularity in the timing, volume, or pattern of menstrual blood flow. This study investigates the histopathological spectrum of endometrial changes across various age groups in patients presenting with AUB as their primary symptom. Materials and Methods: The study analyzed 226 endometrial biopsies/specimens collected over two years from patients with AUB as the main complaint. These specimens were processed, and slides stained with hematoxylin and eosin (H&E) were examined to determine the endometrial patterns. A chi-square test assessed the relationship between age and specific endometrial pathologies. Observations and Results: Most of the 226 cases were from perimenopausal women (40–49 years), representing 57% of the total, with proliferative endometrium being the most common pattern (40.9%). About 20% of the cases were in the reproductive age group (49 years), with endometrioid carcinoma being the most frequent pattern observed. Other endometrial patterns included disordered proliferative endometrium, endometritis, endometrial polyps, Arias–Stella reaction, and progesterone effects. Conclusion: Patients with AUB present with a wide range of endometrial patterns, from normal cyclic endometrium to malignancies. Histopathological examination remains the gold standard for diagnosing AUB, showing a significant association between endometrial lesions and age.

Epithelial-mesenchymal transition (EMT), which is well known for its role in embryonic development, malignant transformation, and tumor progression, has also been implicated in a variety of retinal diseases, including proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), and diabetic retinopathy. EMT of the retinal pigment epithelium (RPE), although important in the pathogenesis of these retinal conditions, is not well understood at the molecular level. We and others have shown that a variety of molecules, including the co-treatment of human stem cell-derived RPE monolayer cultures with transforming growth factor beta (TGF-β) and the inflammatory cytokine tumor necrosis factor alpha (TNF-α), can induce RPE-EMT; however, small molecule inhibitors of RPE-EMT have been less well studied. Here, we demonstrate that BAY651942, a small molecule inhibitor of nuclear factor kapa-B kinase subunit beta (IKKβ) that selectively targets NF-κB signaling, can modulate TGF-β/TNF-α-induced RPE-EMT. Next, we performed RNA-seq studies on BAY651942 treated hRPE monolayers to dissect altered biological pathways and signaling events. Further, we validated the effect of IKKβ inhibition on RPE-EMT-associated factors using a second IKKβ inhibitor, BMS345541, with RPE monolayers derived from an independent stem cell line. Our data highlights the fact that pharmacological inhibition of RPE-EMT restores RPE identity and may provide a promising approach for treating retinal diseases that involve RPE dedifferentiation and EMT.

Proliferative verrucous leukoplakia (PVL) is a rare, aggressive form of oral leukoplakia with a substantial risk of malignant transformation. The slowly progressive course and the lack of a single defining histopathologic characteristic for PVL make this entity a diagnostic challenge. We report on a patient who presented with a 7-year history of worsening oral lesions.

Background/aim Diabetic retinopathy (DR) is one of the leading causes of blindness in people whose ages range from 20 to 64 worldwide. This study aims to evaluate the association of serum 25-hydroxy (OH) vitamin D deficiency and DR in type 2 diabetes mellitus (T2DM) patients. Patients and methods A cross-sectional study was conducted on 90 Egyptian patients with T2DM. Patients were divided into two groups: group I included 44 patients without retinopathy and group II included 46 with retinopathy. Group II was subdivided into two subgroups, group IIa, which included 26 nonproliferative DR patients and group IIb, which included 20 proliferative DR patients. Anthropometric data and laboratory investigations, including fasting and the postprandial blood sugar, glycated hemoglobin, lipid profiles, and serum vitamin D level. A fundus examination was also performed. Results The present results exhibited a significant decrease (P

Huanhuan Zhu, Chen Chen, Luhan Geng, Qing Li, Chengning Zhang, Lin Wu, Bo Zhang, Suyan Duan,&ast; Changying Xing,&ast; Yanggang Yuan&ast; Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanggang Yuan, Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Tel/Fax +86-25-6813-6462, Email ygyuan@njmu.edu.cnBackground: Mounting evidence suggests that mitochondrial dysfunction contributes to lupus nephritis (LN) pathogenesis. Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) mediating pyruvate transport from the cytoplasm to the mitochondrial matrix, determines the cell survival and cellular energy supply. Here, we aimed to investigate the association of mitochondrial pyruvate carrier expression with the clinical and histological features in LN.Methods: Patients with biopsy-proven proliferative LN (class III and class IV, n=18) and membranous LN (class V, n=18) were included. Expression of MPC1 and MPC2 were examined by immunohistochemistry. MPC protein levels in the two groups were evaluated by the Student’s t-test. Correlation analysis between MPC levels and clinicopathological features was performed by Spearman’s rank correlation.Results: Both MPC1 and MPC2 were exclusively expressed in renal tubules of enrolled LN. Significantly lower MPC1 and MPC2 were observed in patients with proliferative LN compared to membranous LN. In addition, the MPC1 and MPC2 were negatively correlated with SLEDAI-2K score, renal function, and renal pathology activity index.Conclusion: Both MPC1 and MPC2 were localized in renal tubules, and decreased MPC content was more pronounced in proliferative LN than membranous LN. MPC levels were significantly correlated with renal functions and renal pathology activity.Keywords: lupus nephritis, mitochondrial pyruvate carrier, proliferative, membranous, tubulointerstitial lesions

Hong-Mei Li,&ast; Wei Huang,&ast; Chao Hu, Zi-Shu Zhang, Yu-Dong Xiao, Tian-Cheng Wang Department of Radiology, the Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian-Cheng Wang; Yu-Dong Xiao, Tel +8613637403027, Fax +86 0731-85533525, Email wangtiancheng94@csu.edu.cn; xiaoyudong222@csu.edu.cnPurpose: There is a scarcity of predictive models currently accessible for prognosticating proliferative hepatocellular carcinoma (HCC), an integrated class of subtype, characterized by a dismal prognosis. Consequently, this study aimed to develop and validate a novel prognostic model capable of accurately predicting the prognosis of proliferative HCC after curative resection.Patients and Methods: This retrospective multicenter study included patients with solitary HCC who underwent curative liver resection from August 2014 to December 2020 (n = 816). Patients were stratified into either the proliferative HCC cohort (n = 259) or the nonproliferative HCC cohort (n = 557) based on histological criteria. Disease-free survival (DFS) was compared between the two groups before and after one-to-one propensity score matching (PSM). Of all the proliferative HCC patients, 203 patients were assigned to training cohort, and 56 patients were assigned to validation cohort. Univariate and multivariate analyses were performed in training cohort to identify risk factors associated with worse DFS. Thereafter, a predictive model was constructed, subsequently validated in the validation cohort.Results: The DFS of proliferative HCC was significantly worse than nonproliferative HCC before and after PSM. Meanwhile, multivariate regression analysis revealed that liver cirrhosis (P = 0.032) and larger tumor size (P = 0.000) were independent risk factors of worse DFS. Lastly, the discriminative abilities of the predictive model for 1, 3, 5-year DFS rates, as determined by receiver operating characteristic (ROC) curves, were 0.702, 0.720, and 0.809 in the training cohort and 0.752, 0.776, and 0.851 in the validation cohort, respectively.Conclusion: This study developed a predictive model with satisfactory accuracy to predict the worse DFS in proliferative HCCs after liver resection. Moreover, this predictive model may serve as a valuable tool for clinicians to predict postoperative HCC recurrence, thereby enabling them to implement early preventative strategies.Keywords: hepatocellular carcinoma, proliferative, nonproliferative, predictive model, curative resection

Aims: To determine the prevalence and predictors of diabetic retinopathy (DR) in Saudi males and females with diabetes. Methods: This cross-sectional study enrolled 507 patients with diabetes between May and August 2018. The data extracted from patients’ records included demographic and clinical information and laboratory investigations. The retinopathy data were based on fundus photography graded into five categories: no DR, NPDR, MNPDR, SNPDR, and PDR. Results: The patients’ mean age was 47.3 years, the majority (59.3%) being female and T2DM being the most common type (52.4%). The prevalence of no DR was 51.4%; NPDR, 4.4%; MNPDR, 7.7%; SNPDR, 3.7%; and PDR, 5.1%. The duration of DM, as well as the severity of hypertension and neuropathy values rose significantly as DR progressed, underlining the pivotal role of hyperglycemia as the primary driver of diabetic complications. The odds ratio for the presence of hypertension was 1.8 (95% CI 0.9–3.5); hypertension showed the highest risk of DR. Stratification according to gender showed a significantly higher DR risk in females than males. Interestingly, nephropathy played a significant role in the DR risk in T1DM. Conclusions: Among T1DM and T2DM patients, the severity of DR is associated with risk factors including the DM duration, hyperglycemia, hypertension, and neuropathy. The impact of these factors varies with gender and diabetes type. Therefore, the severity of DR could define patients at a high risk of macro/microvascular complications and enable earlier interventions to reduce morbidity and mortality among T1DM and T2DM patients.

Abstract Background To investigate the viscoelastic signatures of proliferative hepatocellular carcinoma (HCC) using three-dimensional (3D) magnetic resonance elastography (MRE). Methods This prospective study included 121 patients with 124 HCCs as training cohort, and validation cohort included 33 HCCs. They all underwent preoperative conventional magnetic resonance imaging (MRI) and tomoelastography based on 3D multifrequency MRE. Viscoelastic parameters of the tumor and liver were quantified as shear wave speed (c, m/s) and loss angle (φ, rad), representing stiffness and fluidity, respectively. Five MRI features were evaluated. Multivariate logistic regression analyses were used to determine predictors of proliferative HCC to construct corresponding nomograms. Results In training cohort, model 1 (Combining cirrhosis, hepatitis virus, rim APHE, peritumoral enhancement, and tumor margin) yielded an area under the curve (AUC), sensitivity, specificity, accuracy of 0.72, 58.73%,78.69%, 67.74%, respectively. When adding MRE properties (tumor c and tumor φ), established model 2, the AUC increased to 0.81 (95% CI 0.72–0.87), with sensitivity, specificity, accuracy of 71.43%, 81.97%, 75%, respectively. The C-index of nomogram of model 2 was 0.81, showing good performance for proliferative HCC. Therefore, integrating tumor c and tumor φ can significantly improve the performance of preoperative diagnosis of proliferative HCC (AUC increased from 0.72 to 0.81, p = 0.012). The same finding was observed in the validation cohort, with AUC increasing from 0.62 to 0.77 (p = 0.021). Conclusions Proliferative HCC exhibits low stiffness and high fluidity. Adding MRE properties (tumor c and tumor φ) can improve performance of conventional MRI for preoperative diagnosis of proliferative HCC. Critical relevance statement We investigated the viscoelastic signatures of proliferative hepatocellular carcinoma (HCC) using three-dimensional (3D) magnetic resonance elastography (MRE), and find that adding MRE properties (tumor c and tumor φ) can improve performance of conventional MRI for preoperative diagnosis of proliferative HCC. Graphical Abstract

Proliferative lupus nephritis, which is diagnosed by renal biopsy, has significant impact on the treatment choices and long-term prognosis of juvenile SLE (jSLE). Renal biopsies are however not always possible or available, thus leading to an ongoing search for alternative biomarkers. This study aimed to develop a clinical predictive machine learning model using routine standard parameters as an alternative tool to evaluate the probability of proliferative lupus nephritis (ISN/RPS Class III or IV). Data were collected retrospectively from jSLE patients seen at Selayang Hospital from 2004 to 2021. A total of 22 variables including demographic, clinical and laboratory features were analyzed. A recursive feature elimination technique was used to identify factors to predict pediatric proliferative lupus nephritis. Various models were then used to build predictive machine learning models and assessed for sensitivity, specificity and accuracy. There were 194 jSLE patients (165 females), of which 111 had lupus nephritis (54 proliferative pattern). A combination of 11 variables consisting of gender, ethnicity, fever, nephrotic state, hypertension, urine red blood cells (RBC), C3, C4, duration of illness, serum albumin, and proteinuria demonstrated the highest accuracy of 79.4% in predicting proliferative lupus nephritis. A decision-tree model performed the best with an AROC of 69.9%, accuracy of 73.85%, sensitivity of 78.72% and specificity of 61.11%. A potential clinically useful predictive model using a combination of 11 non-invasive variables to collectively predict pediatric proliferative lupus nephritis in daily practice was developed.

Diabetic Retinopathy (DR) is a micro vasculardisorder that affects the eyes and is a long term effectofDiabetesmellitus. The likelihood to develop diabetic retinopathy is directly proportional to the age and duration of the diabetes, as well as increase in the level of blood glucose level and fluctuation in blood pressure levels. A person who has diabetes has more probability to develop diabetic retinopathy. The ration of people with diabetes started to increase from 285 million in 2010 and will reach up to 439 million in the year of 2030.Out of the total number of people with Diabetic Retinopathy, approximately one-fourth of the people have vision-threatening disease. Earlier detection and classificationof Diabetic Retinopathy has to be taken much care in order to sustain a patient’s vision. The diabetic Retinopathy may be classified into various stages like Mild non-proliferative retinopathy, Moderate nonproliferative retinopathy, severe nonproliferative Retinopathy and Proliferative diabetic retinopathy. Theproblem associated with the manual detection of diabetic retinopathy is that the processing time is high, effortconsumingandrequiresanophthalmologist to examine the eye retinal fund us images. The manual analysis includes Visual Acuity testing, Tonometry and Pupil dilation. The vision lost due to Diabetic retinopathy is sometimes irreparable. Hence there is a need for earlier detection and treatment to reduce the risk of blindness.Hence there are various automated methods of diabetic retinopathy screening that have made good progress using image classification, pattern recognition, and machine learning. The input to the automated image classification model can be the color fundus photography or optical Coherence tomography images.

PurposeTo compare the efficiency of releasable scleral buckling (RSB) and pars plana vitrectomy (PPV) in the treatment of phakic patients with primary rhegmatogenous retinal detachment.MethodsThe current study was a prospective randomized clinical trial. One hundred and ten eyes from 110 patients with primary rhegmatogenous retinal detachment and proliferative vitreoretinopathy of Grade B or less were included in this study. The patients were randomly allocated into an RSB group and a PPV group. The functional and anatomical success was compared between groups.ResultsThe primary anatomical success rate (PPV 41/43 [95.35%] and RSB 38/41 [92.68%]) and final anatomical success rate (PPV and RSB 100%) showed a nonsignificant difference. The best-corrected visual acuity, intraocular pressure, and complications were not different between the groups. However, the incidence of cataract progression was higher in the PPV group (26 of 43 [60.47%]) than in the RSB group (4 of 41 [9.76%]) at the 12-month follow-up. The subfoveal choroidal thickness increased significantly in the RSB group 3 months after surgery, but no longer differed at the postoperative 6-month and 12-month follow-ups. The axial length had increased significantly 1 month after surgery, but the difference was no longer significant at 3 months, 6 months, and 12 months.ConclusionThe RSB and PPV procedures have the same effects on the functional and anatomical success for patients with phakic primary rhegmatogenous retinal detachment. Nevertheless, based on the few cases of intraocular complications and cataract progression, we believe that the RSB technique should be preferentially recommended.

Proliferative vitreoretinopathy (PVR) is a significant threat for vision recovery from retinal detachment or ocular trauma. Currently, no approved pharmacological intervention to prevent PVR. Daunorubicin (DNR) and dexamethasone (DEX) were sequentially loaded into oxidized porous silicon (pSiO2) particles by covalent conjugation. The DNR + DEX-loaded particles, and control particles loaded with DNR only and DEX only were incubated with RPE-populated collagen for daily gel surface quantitation. Toxicity was monitored by ophthalmic examinations and histological evaluation 21 days after injection. At 3rd week following intravitreal injection, a localized retinal detachment (RD) was created by subretinal injection of Healon in all pretreated eyes in addition to 3 non-interventional control eyes. 10 µg of bromodeoxyuridine (BrdU) was injected into the vitreous 4 h before sacrifice on day 3 after RD induction. Retinal sections were stained for glial fibrillary green protein (GFAP) and BrdU to identify activated glial cells and retinal cell proliferation. The studies demonstrated that all three pSiO2 particle types were well tolerated in vivo. DNR alone and DNR + DEX combination formulations demonstrated equally strong suppression on gel contraction (least square mean area of the gel: control = 1.71 vs. 30DNR = 1.85 or 30/40Dual = 1.83, p

This article discusses a retrospective case-control study that compares the prevalence of psychiatric illness in young patients with type 1 diabetes and proliferative diabetic retinopathy (PDR) who undergo either pars plana vitrectomy (PPV) surgery or panretinal photocoagulation (PRP) laser treatment. The study found that patients who underwent surgery had a higher prevalence of psychiatric diagnoses compared to those who received laser treatment alone. The article emphasizes the need for further research to understand the relationship between PDR and psychiatric illness and highlights the importance of physicians and ophthalmologists being aware of the potential impact of psychiatric illness on diabetic control. [Extracted from the article]

Proliferative glomerulonephritis in myelofibrosis is a very rare. Mesangial proliferation and sclerosis with changes of chronic thrombotic microangiopathy have been reported, but pauci-immune focal crescentic glomerulonephritis has not been described so far. Herein, we present a 68-year-old male who was a known case of myelofibrosis and presented with rapidly progressive glomerulonephritis and nephrotic range proteinuria. He was diagnosed as anti-neutrophil cytoplasmic antibody (ANCA)-negative focal crescentic glomerulonephritis, and he responded well to a course of intravenous methylprednisolone and cyclophosphamide. Pauci-immune focal crescentic glomerulonephritis may occur in myelofibrosis without ANCA and may be related to unknown pathogenetic mechanisms in myeloproliferative disorders or suggest any superimposed pathology that might respond well to immunosuppressants. [ABSTRACT FROM AUTHOR]

BackgroundKeloids are defined as a benign dermal fibroproliferative disorder with no malignant potential. They tend to occur following trivial trauma or any form of trauma in genetically predisposed individuals. Keloids are known to grow beyond the margins of the wound and are common in certain body parts. The pathophysiology of keloid remains unclear, and fibroblasts have been presumed to be the main cells involved in keloid formation. Understanding the mechanism(s) of keloid formation could be critical in the identification of novel therapeutic regimen for the treatment of the keloids.ObjectiveTo review the pertinent literature and provide updated information on keloid pathophysiology.Data sourceA Medline PubMed literature search was performed for relevant publications.ResultsA total of 66 publications were retrieved, with relevant publications on the etiology and pathogenesis as well as experimental studies on keloids. All articles were critically analyzed, and all the findings were edited and summarized.ConclusionThere is still no consensus as on what is the main driving cell to keloid formation. One may, however, hypothesize that keloid formation could be a result of an abnormal response to tissue injury, hence resulting in an exaggerated inflammatory state characterized by entry of excessive inflammatory cells into the wound, including macrophages, lymphocytes, and mast cells. These cells seem to release cytokines including transforming growth factor β1 that stimulate fibroblasts to synthesize excess collagen, which is a hallmark of keloid disease.

Background: To investigate the viscoelastic signatures of proliferative hepatocellular carcinoma (HCC) using three-dimensional (3D) magnetic resonance elastography (MRE). Methods: This prospective study included 121 patients with 124 HCCs as training cohort, and validation cohort included 33 HCCs. They all underwent preoperative conventional magnetic resonance imaging (MRI) and tomoelastography based on 3D multifrequency MRE. Viscoelastic parameters of the tumor and liver were quantified as shear wave speed (c, m/s) and loss angle (φ, rad), representing stiffness and fluidity, respectively. Five MRI features were evaluated. Multivariate logistic regression analyses were used to determine predictors of proliferative HCC to construct corresponding nomograms. Results: In training cohort, model 1 (Combining cirrhosis, hepatitis virus, rim APHE, peritumoral enhancement, and tumor margin) yielded an area under the curve (AUC), sensitivity, specificity, accuracy of 0.72, 58.73%,78.69%, 67.74%, respectively. When adding MRE properties (tumor c and tumor φ), established model 2, the AUC increased to 0.81 (95% CI 0.72–0.87), with sensitivity, specificity, accuracy of 71.43%, 81.97%, 75%, respectively. The C-index of nomogram of model 2 was 0.81, showing good performance for proliferative HCC. Therefore, integrating tumor c and tumor φ can significantly improve the performance of preoperative diagnosis of proliferative HCC (AUC increased from 0.72 to 0.81, p = 0.012). The same finding was observed in the validation cohort, with AUC increasing from 0.62 to 0.77 (p = 0.021). Conclusions: Proliferative HCC exhibits low stiffness and high fluidity. Adding MRE properties (tumor c and tumor φ) can improve performance of conventional MRI for preoperative diagnosis of proliferative HCC. Critical relevance statement: We investigated the viscoelastic signatures of proliferative hepatocellular carcinoma (HCC) using three-dimensional (3D) magnetic resonance elastography (MRE), and find that adding MRE properties (tumor c and tumor φ) can improve performance of conventional MRI for preoperative diagnosis of proliferative HCC. Key points: HCC demonstrates a distinct viscoelasticity signature on 3D MRE. Proliferative HCC exhibits low stiffness and high fluidity. Combining MRE properties can improve the preoperative diagnostic performance of proliferative HCC. [ABSTRACT FROM AUTHOR]

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Four Lactiplantibacillus plantarum strains newly isolated and identified from human breast milk in Türkiye, have probiotic, functional and proliferative inhibition potential of metabolites against colon cancer cell lines were evaluated. In simulated gastric and intestinal media, all strains exhibited strong probiotic character by showing resistance, although decreasing with time and concentration. The strains were sensitive to penicillin G, rifampin and chloramphenicol and showed antibacterial effect on all pathogenic bacteria. Citric acid, malic acid, tartaric acid, pyruvic acid and fumaric acid were not detected in the strains, while the highest amount of acetic acid was detected. The quantitative-qualitative analysis and structural characterization of exopolysaccharide (EPS) was confirmed and it was determined that the strains synthesized similar amounts. Compared to standard antioxidants, the strains showed less DPPH activity and similar ABTS activity. High amounts of metabolites of the strains showed good antiproliferative effect on Caco-2, while lower amounts showed good antiproliferative effect on the HT-29 cell line. When all the data were considered, it was determined that the strains were close to each other, but the YAAS 23 strain showed slightly better properties. In conclusion, breast milk is a unique environment harboring beneficial bacteria such as L. plantarum for human health. • Four Lactiplantibacillus plantarum strains were isolated from human breast milk. • Probiotic properties may vary among strains. • Differences among strains may affect the amount of metabolite synthesis. • Metabolites synthesized by strains exhibit different biological activities. • EPS was confirmed by quantitative-qualitative analysis and structural characterization. [ABSTRACT FROM AUTHOR]

Degeneration of retinal astrocytes precedes hypoxia-driven pathologic neovascularization and vascular leakage in ischemic retinopathies. However, the molecular events that underlie astrocyte loss remain unclear. Astrocytes abundantly express connexin 43 (Cx43), a transmembrane protein that forms gap junction (GJ) channels and hemichannels. Cx channels can transfer toxic signals from dying cells to healthy neighbors under pathologic conditions. Here we show that Cx43 plays a critical role in astrocyte apoptosis and the resulting preretinal neovascularization in a mouse model of oxygen-induced retinopathy. Opening of Cx43 hemichannels was not observed following hypoxia. In contrast, GJ coupling between astrocytes increased, which could lead to amplification of injury. Accordingly, conditional deletion of Cx43 maintained a higher density of astrocytes in the hypoxic retina. We also identify a role for Cx43 phosphorylation in mediating these processes. Increased coupling in response to hypoxia is due to phosphorylation of Cx43 by casein kinase 1δ (CK1δ). Suppression of this phosphorylation using an inhibitor of CK1δ or in site-specific phosphorylation-deficient mice similarly protected astrocytes from hypoxic damage. Rescue of astrocytes led to restoration of a functional retinal vasculature and lowered the hypoxic burden, thereby curtailing neovascularization and neuroretinal dysfunction. We also find that absence of astrocytic Cx43 does not affect developmental angiogenesis or neuronal function in normoxic retinas. Our in vivo work directly links phosphorylation of Cx43 to astrocytic coupling and apoptosis and ultimately to vascular regeneration in retinal ischemia. This study reveals that targeting Cx43 phosphorylation in astrocytes is a potential direction for the treatment of proliferative retinopathies.

Objective: To assess the major risk factors of diabetic retinopathy in patients presenting to the eye OPD of the Holy Family Hospital, Rawalpindi. Study Design: Descriptive Cross-sectional study. Setting: Department of Ophthalmology, Holy Family Hospital, Rawalpindi. Period: March 2018 to September 2018. Material & Methods: 330 patients presenting at the diabetic clinic of Holy Family Hospital aged between 30-70 years with both type I and type II diabetes for ≥5 years (diagnosed by checking fasting blood sugar or HbA1C). History including age, gender, weight, height, duration of diabetes mellitus and control of diabetes mellitus was taken on a pre-designed proforma. Slit lamp examination was performed by the consultant ophthalmologist to check for Diabetic Retinopathy (NPDR and PDR). Results: Mean age of the patients was 50.4±9.8. Patients were distributed according to the age groups showing that 56(56%) of the patients were diabetics, 61(49.9%) with NPDR and 48(48%) with PDR in the 30-50 year group. While 51-70 year group included 44(44%) diabetics, 69(53.1%) with NPDR and 52(52%) with PDR. There was no significant association between history of hypertension and diabetic retinopathy (p=0.804) or BMI and diabetic retinopathy (p=0.451). There was significant association between diabetic retinopathy and duration of diabetes (p=0.035) as well as diabetic retinopathy and Hb1Ac levels (p=0.001). Gender variations were statistically significant (p=0.001), with females being more affected than males. Conclusion: Diabetic retinopathy is strongly associated with female gender, longer duration of diabetes and poor glycemic control. [ABSTRACT FROM AUTHOR]

Abstract Background High-grade serous ovarian carcinoma (HGSOC) is classified into four molecular subtypes; mesenchymal, proliferative, immunoreactive, and differentiated, with suggested different prognosis. Addressing the presence of histopathological and immunohistochemical differences in HGSOC that parallel the molecular subtypes can help in tailoring the management protocol to improve therapeutic response and patient outcome. Methods This retrospective study was conducted on 85 specimens for cases of HGSOC. Cases were classified according to histopathological findings into mesenchymal, proliferative, immunoreactive, and differentiated subtypes. Cases were immunostained with ER, PR, Ki67, CD8, E-cadherin, and vimentin. Results By applying histopathological data, cases were subdivided into 4 groups; mesenchymal type represented by 25 cases, proliferative type which included 14 cases, the immunoreactive type included 14 cases, and differentiated type represented by 32 cases; 13 of them had SET features and 19 had papillary architectural features. A significant correlation was found between Ki67 and proliferative subtype, as well as between CD8 and immunoreactive subtype. ER showed significantly higher expression in proliferative subtype in the group treated by primary debulking. CD8 showed a significant correlation with solid endometroid transitional (SET) pattern in the group that underwent interval debulking. In terms of prognosis, the shortest median progression-free survival (PFS) was for mesenchymal subtype, while the longest median PFS was for differentiated subtype with SET architectural pattern with statistically significant correlation. No correlation was found between any of the studied parameters and overall survival. Conclusion Histopathological features and immunohistochemistry can help to stratify HGSOC into prognostic distinct groups.

Blinding retinal diseases become more epidemic as the population ages. These diseases, such as diabetic retinopathy and macular edema, are of chronic nature and require protracted drug presence at the disease site. A sustained intravitreal porous silicon delivery system with dexamethasone (pSiO2-COO-DEX) was evaluated in a new rabbit model of proliferative vitreoretinopathy (PVR) in a real treatment design. In contrast to the pretreatment design model, pSiO2-COO-DEX was intravitreally injected into the eyes with active inflammation. Subretinal injection of vascular endothelial growth factor (VEGF) and Matrigel induced a late-onset vitreoretinal inflammation that gradually developed into PVR. This method mimics the human disease better than PVR induced by either intravitreal cell injection or trauma. The pSiO2-COO-DEX intervened eyes had minimal PVR, while balanced saline solution or free dexamethasone intervened eyes had significantly more PVR formation. In addition, adding VEGF to the Matrigel for subretinal injection induced greater inflammation and retinal neovascularization in comparison to only Matrigel injected under the medullary ray. Clinical and pathological examinations, including fundus fluorescein angiography and optical coherence tomography, confirmed these changes. In the current study, neither subretinal injection of Matrigel or subretinal injection of VEGF and Matrigel induced choroidal neovascularization. However, the current PVR model demonstrates a chronic course with moderate severity, which may be useful for drug screening studies.

Proliferative vitreoretinopathy (PVR) is a blinding eye disease and there is no effective pharmacological measure to prevent PVR development. The difficulty comes from lack of potent antiproliferative agent and lack of sustained delivery to cover high-risk time window for PVR to develop. Lipid prodrug of PMEG, hexadecyloxypropyl 9-[(2-phosphonomethoxy)ethyl]guanine (HDP-PMEG), was prepared and was evaluated as a pharmacological adjuvant to surgical management of PVR. A dose-escalation study determined that the highest nontoxic dose for intravitreal use in pigmented rabbits was 3 µg per eye. The genotoxicity of HDP-PMEG was harnessed as a perioperative preventative measure against PVR in a rabbit eye model while the sustained intravitreal pharmacological effect was evaluated on a laser-induced fibrovascular model in rat eye. After intravitreal 3 µg, HDP-PMEG particles in the rabbit vitreous was visible for at least 6 weeks. A single 50-min intravitreal infusion of HDP-PMEG demonstrated significant inhibition of PVR formation when compared with the eyes infused with only BSS (BSS vs. HDP-PMEG: estimate = 1.14, OR = 3.1, p = .027). A single intravitreal 104 ng (equivalent to 3 µg for rabbit eye) of HDP-PMEG significantly inhibit laser-induced fibrovascular proliferation in rat eye by 55% (least square mean pixel, BSS = 4763569.5 vs. HDP-PMEG = 2148129.7, p

This study analyzed the transcriptional changes in primary human corneal stromal fibroblasts (hCSFs) grown under quiescent (serum-free) and proliferating (serum-supplemented) culture conditions to identify genes, pathways, and protein‒protein interaction networks influencing corneal repair and regeneration. Primary hCSFs were isolated from donor human corneas and maintained in serum-free or serum-laden conditions. RNA was extracted from confluent cultures using Qiagen kit and subjected to RNA sequencing (RNAseq) analysis. Differential gene expression (DGE) and pathway enrichment analyses were conducted using DESeq2 and Gene Set Enrichment Analysis (GSEA), respectively. Protein‒protein interaction (PPI) networks were created exploiting the STRING database and analyzed with Cytoscape and the cytoHubba plugin. RNA-seq revealed 5,181 genes that were significantly differentially expressed/changed among the 18,812 annotated genes (p value ˂0.05). A cutoff value of a log2-fold change of ±1.5 or greater was used to identify 674 significantly upregulated and 771 downregulated genes between quiescent and proliferating hCSFs. Pathway enrichment analysis revealed significant changes in genes linked to cell cycle regulation, inflammatory, and oxidative stress response pathways, such as E2F Targets, G2M Checkpoint, and MYC Targets, TNFA signaling via NF-kB, and oxidative phosphorylation. Protein-protein interaction network analysis highlighted critical hub genes. The FGF22, CD34, ASPN, DPT, LUM, FGF10, PDGFRB, ECM2, DCN, VEGFD, OMD, OGN, ANGPT1, CDH5, and PRELP were upregulated, whereas genes linked to cell cycle regulation and mitotic progression, such as BUB1, TTK, KIF23, KIF11, BUB1B, DLGAP5, NUSAP1, CCNA2, CCNB1, BIRC5, CDK1, KIF20A, AURKB, KIF2C, and CDCA8, were downregulated. The RNA sequences and gene count files have been submitted to the Gene Expression Omnibus (accession # GSE260476). Our study provides a comprehensive information on the transcriptional and molecular changes in hCSFs under quiescent and proliferative conditions and highlights key pathways and hub genes. • Total 5,181 significantly regulated genes between quiescent and proliferating hCSFs, show serum's impact on gene expression • The key enriched pathways in the quiescent-hCSFs are related to cell cycle regulation and stress response • Most enriched pathways include E2F Targets, G2M Checkpoint, MYC Targets, TNFA signaling, and oxidative phosphorylation • The study emphasizes the roles of cell cycle and stress response pathways in quiescent-hCSFs [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR), a progressive condition due to diabetes that can lead to blindness, is typically characterized by a number of stages, including non-proliferative (mild, moderate and severe) and proliferative DR. These stages are marked by various vascular abnormalities, such as intraretinal microvascular abnormalities (IRMA), neovascularization (NV), and non-perfusion areas (NPA). Automated detection of these abnormalities and grading the severity of DR are crucial for computer-aided diagnosis. Ultra-wide optical coherence tomography angiography (UW-OCTA) images, a type of retinal imaging, are particularly well-suited for analyzing vascular abnormalities due to their prominence on these images. However, accurate detection of abnormalities and subsequent grading of DR is quite challenging due to noisy data, presence of artifacts, poor contrast and subtle nature of abnormalities. In this work, we aim to develop an automated method for accurate grading of DR severity on UW-OCTA images. Our method consists of various components such as UW-OCTA scan quality assessment, segmentation of vascular abnormalities and grading the scans for DR severity. Applied on publicly available data from Diabetic retinopathy analysis challenge (DRAC 2022), our method shows promising results with a Dice overlap metric and recall values of 0.88 for abnormality segmentation, and the coefficient-of-agreement (κ) value of 0.873 for DR grading. We also performed a radiomics analysis, and observed that the radiomics features are significantly different for increasing levels of DR severity. This suggests that radiomics could be used for multimodal grading and further analysis of DR, indicating its potential scope in this area. • Proposed an automated method for accurate grading of DR severity on UW-OCTA images. • Performs quality assessment, vascular abnormality segmentation and DR grading. • Our method achieved recall values of 0.88 for vascular abnormality segmentation. • For DR grading, our method achieved coefficient-of-agreement value (kappa) of 0.873. • The radiomics features differed significantly for increasing levels of DR severity. [ABSTRACT FROM AUTHOR]

Case series of seven patients with ischemic retinopathy displaying a smokestack leakage pattern on fundus fluorescein angiography outside the clinical setting of central serous chorioretinopathy. Purpose: To report a series of cases with smokestack leakage on fundus fluorescein angiography outside the clinical setting of central serous chorioretinopathy. Methods: A multicenter, observational retrospective case series evaluating fundus fluorescein angiography on Topcon and Optos systems. Results: Seven patients with neovascularization due to ischemic retinopathy demonstrated a unique smokestack pattern of angiographic leakage. The patients' ages ranged between 44 and 71 years and were seen at 3 academic teaching hospitals in the Washington–Baltimore metropolitan area. Five patients had been diagnosed with proliferative diabetic retinopathy, one with sickle cell ischemic retinopathy, and one with branch retinal artery occlusion; none of the patients had a known history or clinical signs of current or past central serous chorioretinopathy. Conclusion: This is the first published case series to the author's knowledge of ischemic retinopathy displaying a smokestack leakage pattern on fundus fluorescein angiography that is classically described with idiopathic central serous chorioretinopathy. [ABSTRACT FROM AUTHOR]

Machine learning and deep learning methods have become exponentially more accurate. These methods are now as precise as experts of respective fields, so it is being used in almost all areas of life. Nowadays, people have more faith in machines than men, so, in this vein, deep learning models with the concept of transfer learning of CNN are used to detect and classify diabetic retinopathy and its different stages. The backbone of various CNN-based models such as InceptionResNetV2, InceptionV3, Xception, MobileNetV2, VGG19, and DenceNet201 are used to classify this vision loss disease. In these base models, transfer learning has been applied by adding some layers like batch normalization, dropout, and dense layers to make the model more effective and accurate for the given problem. The training of the resulting models has been done for the Kaggle retinopathy 2019 dataset with about 3662 fundus fluorescein angiography colored images. Performance of all six trained models have been measured on the test dataset in terms of precision, recall, F1 score, macro average, weighted average, confusion matrix, and accuracy. A confusion matrix is based on maximum class probability prediction that is the incapability of the confusion matrix. The ROC-AUC of different classes and the models are analyzed. ROC-AUC is based on the actual probability of different categories. The results obtained from this study show that InceptionResNetV2 is proven the best model for diabetic retinopathy detection and classification, among other models considered here. It can work accurately in case of less training data. Thus, this model may detect and classify diabetic retinopathy automatically and accurately at an early stage. So it would be beneficial for humans to reduce the effects of diabetes. As a result of this, the impact of diabetes on vision loss can be minimized, and that would be a blessing in the medical field. [ABSTRACT FROM AUTHOR]

Purpose: To determine how photopic negative response (PhNR) of elctroretinogram (ERG) is affected in diabetes subjects with and without retinopathy and to compare it with the controls in Indian subjects. Methods: Fifty-nine subjects were divided into control, diabetes with no retinopathy, non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) groups. All subjects photopic ERG parameters were measured using short duration (4 milli seconds) red flashes (1.7 cd..m-2) on blue background (8cd. m-2). Photopic ERG parameters, a-wave amplitude, a-wave implicit time, b-wave amplitude, b-wave implicit time and PhNR amplitudes were measured in all the subjects. Results: 25 eyes of 14 subjects with diabetes, 37 eyes of 30 subjects with various stages of diabetic retinopathy and 24 eyes of 15 age matched control subjects were studied. There is a significant reduction (p < 0.05) in PhNR amplitude along with other ERG parameters such as a-wave amplitude, a-wave implicit time, b-wave amplitude, b-wave implicit time in diabetic retinopathy subjects when compared to control and diabetes subjects but there is no significant difference (p > 0.05) in photopic ERG parameters between controls and diabetic subjects and also between NPDR and PDR subjects. Conclusion: PhNR amplitude along with the other photpic ERG parameters is useful for the evaluation of inner retinal function in cases of diabetic retinopathy when compared to early stages of diabetes. [ABSTRACT FROM AUTHOR]

PurposeTo determine the level of epithelial membrane protein-2 (EMP2) expression in preretinal membranes from surgical patients with proliferative vitreoretinopathy (PVR) or epiretinal membranes (ERMs). EMP2, an integrin regulator, is expressed in the retinal pigment epithelium and understanding EMP2 expression in human retinal disease may help determine whether EMP2 is a potential therapeutic target.MethodsPreretinal membranes were collected during surgical vitrectomies after obtaining consents. The membranes were fixed, processed, sectioned, and protein expression of EMP2 was evaluated by immunohistochemistry. The staining intensity (SI) and percentage of positive cells (PP) in membranes were compared by masked observers. Membranes were categorized by their cause and type including inflammatory and traumatic.ResultsAll of the membranes stained positive for EMP2. Proliferative vitreoretinopathy-induced membranes (all causes) showed greater expression of EMP2 than ERMs with higher SI (1.81 vs. 1.38; P = 0.07) and PP (2.08 vs. 1.54; P = 0.09). However all the PVR subgroups had similar levels of EMP2 expression without statistically significant differences by Kruskal-Wallis test. Inflammatory PVR had higher expression of EMP2 than ERMs (SI of 2.58 vs. 1.38); however, this was not statistically significant. No correlation was found between duration of PVR membrane and EMP2 expression. EMP2 was detected by RT-PCR in all samples (n = 6) tested.ConclusionsAll studied ERMs and PVR membranes express EMP2. Levels of EMP2 trended higher in all PVR subgroups than in ERMs, especially in inflammatory and traumatic PVR. Future studies are needed to determine the role of EMP2 in the pathogenesis and treatment of various retinal conditions including PVR.

Shaarif Bashir,1 Mudassar Hussain,1 Aurangzeb Afzal,2 Usman Hassan,1 Maryam Hameed,1 Sajid Mushtaq1 1Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, 54000, Pakistan; 2Department of Nephrology, Lahore General Hospital, Lahore, 54000, PakistanCorrespondence: Shaarif BashirDepartment of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, PakistanTel +923334245144Email shaarifbashir@yahoo.comBackground: Post-infectious glomerulonephritis (PIGN) (immune complex-mediated glomerulonephritis) and C3 glomerulopathy are sub-types of glomerulonephritis (GN) with hypercellularity. Both have overlapping clinical and morphologic features on a kidney biopsy, however, the treatment and prognosis of these diseases are quite different making their distinction of utmost importance. Immune complex-mediated glomerulonephritis arises from glomerular deposition of immune-complexes (Igs) and C3 as a result of activation of classical (CP) and lectin pathways (LP). C4d is produced as a result of activation of the CP/LP. On the other hand, C3 glomerulopathy results from activation of alternative pathway of complement.Aim: To distinguish between PIGN and C3 glomerulopathy with the help of C4d IHC stain.Materials and Methods: We studied 28 biopsies reported as GN with hypercellularity from January 2015 to January 2020. Clinical information, histological features and immunofluorescence patterns were analyzed. C4d IHC was performed on all the biopsies. Six known cases of immune complex-mediated GN were selected to act as a positive control for C4d staining.Results: Amongst 28 cases originally reported as GN with hypercellularity, 18 were labeled as post-infectious GN and 10 as C3 glomerulopathy based on clinical information and serological findings. 13 of 18 (72.2%) cases of PIGN had mild to moderate (1– 2+) C4d staining, 2 (11.1%) had strong (3+) staining and 3 (16.7%) cases were negative for C4d staining. In the 10 biopsies of C3 glomerulopathy, mild (1+) C4d staining was noted only in 3 (30%) biopsies. C4d had moderate to strong (2– 3+) staining in the control group.Conclusion: C4d IHC stain can be helpful in distinguishing PIGN from C3 glomerulopathy.Keywords: proliferative, post-infectious, C3 glomerulopathy, C4d

Objective To investigate the diagnosis and clinical treatment of maxillofacial connective tissue hyperplastic trichoepithelioma. Methods The clinical data of two cases of maxillofacial connective tissue hyperplastic trichoepithelioma were summarized and analyzed along with the literature. Results Two cases of maxillofacial connective tissue hyperplastic trichoepithelioma were male, aged 21 and 30 years. The clinical manifestations were painless pale brown and pale white plaques in the maxillofacial region. The lesion was tough and clear, with no ulcers in the middle depression. The course was 10-16 months, with 1-3 months before medical treatment, and the tumor had a significant history of enlargement. After surgery, the skin was cut 3 mm along the outer circumference of the tumor, and local tissue defects were repaired by the adjacent flap. The pathological report showed that the tumor cells were located in the dermis, and were striped, trabecular or nested. The tiny sac contained fibrous connective tissue proliferation. The tumor cells were amorphous without obvious nuclear division. Immunohistochemical analysis reported bcl-2(-), CK7(-), CK19(-), CD34(+), P63(+), CK56(+), and Ki67(±). The pathological diagnosis was connective tissue proliferative hair epithelial tumor. The patient was followed up for 24 months. There was no recurrence of the tumor, no obvious scarring, and no deformity or dysfunction of the maxillofacial region. Conclusion Pathological and immunohistochemical examination is the basis for the differential diagnosis of maxillofacial connective tissue hyperplastic trichoepithelioma, and surgical removal of tumors is an effective treatment.

Simple Summary: Ovarian cancer (OC) comprises a heterogeneous group of hormone-dependent diseases with very high mortality. Estrogens have been shown to promote the progression of OC; however, their exact role in OC subtypes remains unknown. Here, we investigated the local estrogen biosynthesis in OC. We performed targeted transcriptomics and estrogen metabolism analyses in high-grade serous OC (HGSOC) cell lines that differed in chemoresistance status and compared these data with publicly available transcriptome and proteome data for HGSOC tissues. In HGSOC cells, estrogen metabolism decreased with increasing chemoresistance. In highly chemoresistant cells and platinum-resistant HGSOC tissues, HSD17B14 expression was increased. Proteome data showed differential levels of HSD17B10, SULT1E1, CYP1B1, and NQO1 between the four HGSOC subtypes. Our results confirm that estrogen biosynthesis differs between different HGSOC cell models and possibly between different HGSOC subtypes. Such differentially expressed enzymes have potential as targets in the search of new treatment options. Ovarian cancer (OC) is highly lethal and heterogeneous. Several hormones are involved in OC etiology including estrogens; however, their role in OC is not completely understood. Here, we performed targeted transcriptomics and estrogen metabolism analyses in high-grade serous OC (HGSOC), OVSAHO, Kuramochi, COV632, and immortalized normal ovarian epithelial HIO-80 cells. We compared these data with public transcriptome and proteome data for the HGSOC tissues. In all model systems, high steroid sulfatase expression and weak/undetected aromatase (CYP19A1) expression indicated the formation of estrogens from the precursor estrone-sulfate (E1-S). In OC cells, the metabolism of E1-S to estradiol was the highest in OVSAHO, followed by Kuramochi and COV362 cells, and decreased with increasing chemoresistance. In addition, higher HSD17B14 and CYP1A2 expressions were observed in highly chemoresistant COV362 cells and platinum-resistant tissues compared to those in HIO-80 cells and platinum-sensitive tissues. The HGSOC cell models differed in HSD17B10, CYP1B1, and NQO1 expression. Proteomic data also showed different levels of HSD17B10, CYP1B1, NQO1, and SULT1E1 between the four HGSOC subtypes. These results suggest that different HGSOC subtypes form different levels of estrogens and their metabolites and that the estrogen-biosynthesis-associated targets should be further studied for the development of personalized treatment. [ABSTRACT FROM AUTHOR]

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Arsenic trioxide (ATO) and statins have been demonstrated to have anti‐neoplastic properties; however, the data regarding their combination therapy is limited. Thus, we aimed to study the effects of ATO, Simvastatin and their combination in proliferation, apoptosis and pathological angiogenesis in prostate cancer cell lines. The human prostate cell lines were treated with different concentrations of Simvastatin and ATO alone and combined to find effective doses and IC50 values. In addition, the percentage of apoptotic cells was evaluated by annexin/PI staining, and mRNA expression levels of the apoptotic gene, including OPN isoforms and VEGF, were investigated using real‐time PCR. Our data displayed that Simvastatin (12 and 8 μM in PC3 and LNCaP cell lines respectively), ATO (8 and 5 μM in PC3 and LNCaP cell lines respectively), and also their combination (12 μM Simvastatin and 8 μM ATO in PC3, 8 μM Simvastatin and 5 μM ATO in LNCaP cell lines respectively) significantly increased the percentage of apoptotic cells. Also, we showed that the combination therapy by Simvastatin and ATO increased cell apoptosis and inhibited cell proliferation, providing anti‐proliferative and anti‐angiogenic properties, possibly via downregulation of the expression of VEGF and OPN genes. These results provide new perceptions regarding the anticancer roles of ATO and statins' combination therapy in prostate cancer. [ABSTRACT FROM AUTHOR]

Previous studies have reported that exosomes bearing certain microRNAs (miRNAs) are related to the physiological functions of different types of cancer cells. Our study aimed to elucidate the role of miR-200a in esophageal squamous cell carcinoma (ESCC). We observed that miR-200a expression is higher in esophageal carcinoma cells, tissues, and exosomes than in normal cells and healthy tissues. We showed that exosome-shuttled miR-200a promotes the proliferation, migration, and invasion of esophageal cells and inhibits apoptosis, thereby leading to the progression of ESCC. We showed that miR-200a exerts its effects through its interaction with Keap1, thus altering the Keap1/Nrf2 signaling pathway. Our results suggest that exosome-shuttled miR-200a might be useful as a biomarker for prognosis in patients with ESCC. [ABSTRACT FROM AUTHOR]

Panretinal photocoagulation in diabetic retinopathy improves oxygen saturation in the retina which results in regression of neovascularisation. This study is aimed at evaluating the plasma levels of angiogenic and angiostatic factors after panretinal photocoagulation for retinopathy. Thirty controls and 29 proliferative diabetic retinopathy subjects who were advised panretinal photocoagulation were recruited for the study. Plasma was collected both before and four weeks after the last dose of the therapy and analysed for angiogenic and angiostatic factors using ELISA technique. The plasma concentration of HIF-1α and VEGF were significantly decreased after laser therapy compared to baseline levels. The plasma concentration of MMP-9 and PEDF was increased significantly after photocoagulation. A significant improvement in the visual acuity was also observed following laser therapy. Panretinal photocoagulation significantly reduced plasma angiogenic and angiostatic factors. These factors may be used to assess therapeutic outcomes in proliferative retinopathy.

Abstract Background To investigate non-histologic factors that can discriminate proliferative lupus nephritis (LN) from membranous LN in patients with systemic lupus erythematosus with renal manifestations. Methods Patients with biopsy-proven proliferative LN (class III ± V and class IV ± V) and membranous LN (class V) were included. Non-histologic factors were compared between the two groups. A logistic regression analysis was performed to identify the factors associated with proliferative LN. To assess the accuracy of these factors in discriminating between proliferative LN and membranous LN, we performed a receiver-operating characteristic analysis. Results Of the total 168 patients with biopsy-proven LN, 150 patients (89.3%) had proliferative LN, and 18 patients (10.7%) had membranous LN. In the multivariable logistic regression analysis, positive anti-double-stranded DNA (anti-dsDNA) antibody (adjusted OR = 11.200, 95% CI = 2.202–56.957, p = 0.004) was associated with proliferative LN, while positive anti-U1RNP antibody (adjusted OR = 0.176, 95% CI = 0.040–0.769, p = 0.021) and higher glomerular filtration rate (GFR) (adjusted OR = 0.973, 95% CI = 0.951–0.994, p = 0.013) were inversely associated with proliferative LN. Among these covariates, the anti-dsDNA antibody (area under the curve = 0.806, 95% CI = 0.695–0.916) had the highest accuracy in discriminating between proliferative LN and membranous LN. Conclusion The positivity of anti-dsDNA antibody was associated with proliferative LN, while the positivity of anti-U1RNP antibody and GFR were inversely associated with proliferative LN. The anti-dsDNA antibody had a good accuracy in discriminating proliferative LN from membranous LN.