Development, validation and application of single molecule molecular inversion probe based novel integrated genetic screening method for 29 common lysosomal storage disorders in India.

BACKGROUND: Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India. RESULTS: 903 smMIPs were designed to target exon and exon-intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood. CONCLUSION: We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.

Genetic alterations in prostate cancer as diagnostic and prognostic markers.

Prostate cancer is the second-most frequently diagnosed cancer in men worldwide. Serum prostatespecific antigen is currently used for the early detection of prostate cancer. However, new biomarkers are needed to decrease over diagnosis and over treatment of prostate cancer due to limitations of prostate-specific antigen. Recently, molecular biomarkers have shown promising results for diagnosis and prognosis of prostate cancer. Molecular biomarkers have improved the sensitivity and specificity of prostate-specific antigen and studies are ongoing to identify molecular biomarkers as a replacement for prostate-specific antigen. This review aims to give an overview of emerging molecular biomarkers for diagnosis and prognosis of prostate cancer.

Design, synthesis, in vitro and in silico bioactivity profiles of new urea/thiourea derivatives of 2-pyridyl piperazine as potent antioxidant and antimicrobial agents: chemo-bio-computational approach.

Synthesis of a series of new urea and thiourea derivatives of 2-pyridyl piperazine was accomplished by reacting various isocyanates and isothiocyanates in the presence of triethylamine (TEA) at 50 °C. All the title compounds were obtained in high yields and their structures were characterized by IR, 1H, 13C NMR, Mass spectral, and Elemental analysis. The synthesized compounds were screened for in vitro and in silico antioxidant and antimicrobial activities. All the title compounds exhibited potent antioxidant and antimicrobial activities. Out of all, 2c and 2f against DPPH, H2O2 and Nitro oxide have exhibited significant activity and the levels of activity were higher than the reference compounds, ascorbic acid and BHT. Whereas 2a, 2c, 2f and 2j have shown prominent activity in terms of zone of inhibition against all the microbial strains tested than the standards such as levofloxacin and nystatin. In addition in silico studies also conveyed the same that is 2a, 2c, 2f and 2j have displayed the highest binding energies against peroxiredoxins and DNA gyrase protein than the standards akin to the rest of the compounds. In overall, 2c and 2f have exhibited most promising antioxidant and antimicrobial activity than the rest of the title compounds in vitro and in silico. Hence, 2c and 2f will stand as a lead and promising antioxidant and antimicrobial drug candidates in future.Communicated by Ramaswamy H. Sarma.

Synthesis, in silico and in vitro anti-cancer studies of phosphorylated derivatives of didanosine targeting MDA-MB-231 breast cancer cell lines.

A series of new phosphorylated derivatives of didanosine were designed, synthesized and evaluated their anticancer effects on human breast cancer cells. Their binding affinities were evaluated against aromatase enzyme and the molecular docking studies demonstrated that 9a, 9h and 9i exhibited high binding interactions than the parent molecule (ddI) and other derivatives; evaluated the aromatase enzyme inhibition. The cell viability, cell proliferation, lactate dehydrogenase showed potential anti-proliferative in dose dependent manner, these results were well correlated with hoesch stain and DNA fragmentation on MDA-MB-231 breast cancer cell lines. Cytotoxicity results disclosed that tryptophan amino acid ester substituted derivative 9i showed potential cell death against MDA-MB-231 cancer cell lines. Furthermore, compound 9i has great potential significance for further investigations (in vivo).

Metabolic risk factors in first acute coronary syndrome (MERIFACS) Study.

OBJECTIVES: In acute coronary syndrome (ACS) patients the focus is on major conventional risk factors - CRF [diabetes, hypertension, elevated low-density cholesterol (LDL-C) and smoking] whereas others - specific metabolic risk factors - MRF [high-density lipoprotein cholesterol (HDL-C), body-mass index (BMI), waist-hip ratio (WHR), and triglycerides, and HbA1c get less attention. METHODS: This is a prospective case-control observational study from 15 tertiary care hospitals in India. CRF and MRF in patients presenting with first incidence of ACS (n = 2153) were compared with matched controls (n = 1210). RESULTS: Propensity score matching (PSM) yielded 1193 cases and matched 1210 controls. Risk factor prevalence in cases vs. controls were CRF: hypertension - 39.4% vs 16.4% (p < 0.0001), diabetes - 42.6% vs 12.7% (p < 0.0001), smoking - 28.3% vs 9.3% (p < 0.0001) and elevated LDL-C - 70.2% vs 57.9% (p < 0.0001). MRF: High BMI - 54.7% vs 55.1% (p = 0.84), increased waist: hip ratio 79.5% vs 63.6% (p < 0.0001), high HbA1c - 37.8% vs 14.9% (p < 0.0001), low HDL-C - 56.2% vs 42.8% (p < 0.0001) and elevated triglycerides - 49.7% vs 44.2% (p = 0.007). Adjusted Odds ratios by multivariate analysis were CRF: hypertension - 2.3 (p < 0.001), diabetes - 4.7 (p < 0.001), high LDL-C - 3.3 (p < 0.001) and smoking- 6.3 (p < 0.001). MRF: High waist: hip ratio - 2.4 (p < 0.001) high HbA1c - 3.2 (p < 0.001), low HDL-C 2.2 (p < 0.001) and elevated triglycerides - 0.878 p = 0.17. CONCLUSION: In India, the risk of ACS conferred by specific metabolic risk factors (High waist: hip ratio, Low HDL-C and High HbA1c) is comparable to that caused by CRF.

The association between diabetes and obesity with Dengue infections.

Dengue, an arboviral disease is a global threat to public health as the number of Dengue cases increases through the decades and this trend is predicted to continue. Non-communicable diseases such as diabetes and obesity are also on an upward trend. Moreover, past clinical studies have shown comorbidities worsen the clinical manifestation of especially Severe Dengue. However, discussion regarding the underlying mechanisms regarding the association between these comorbidities and dengue are lacking. The hallmark of Severe Dengue is plasma leakage which is due to several factors including presence of pro-inflammatory cytokines and dysregulation of endothelial barrier protein expression. The key factors of diabetes affecting endothelial functions are Th1 skewed responses and junctional-related proteins expression. Additionally, obesity alters the lipid metabolism and immune response causing increased viral replication and inflammation. The similarity between diabetes and obesity individuals is in having chronic inflammation resulting in endothelial dysfunction. This review outlines the roles of diabetes and obesity in severe dengue and gives some insights into the plausible mechanisms of comorbidities in Severe Dengue.

Quality changes in fish sausages supplemented with pangas protein isolates as affected by frozen storage and casing material.

Influence of pangas protein isolates (10PI) and casing material on frozen storage (-18 °C) characteristics of pangas mince sausages was studied for a period of three months along with control sausages (CO). The expressible fluid content of sausage emulsion increased as storage progressed to 3 months, reaching 31.32 and 17.57 g 100 g-1 for control and 10% PI emulsions, respectively. Water holding capacity and cooking yield values showed a gradual and significant (p < 0.05) reduction with progress in the storage time. The G' and G″ values decreased during storage, indicating the change in protein structure and gelling ability. Sausages packed in LDPE casings had higher oxidation and bacterial counts than sausages packed in cellulose casings. Irrespective of the casing material and protein isolates, the sensory scores varied non-significantly in all the sausages during the initial storage phase. After three months, sausages from COCL and 10PICL were still acceptable with sensory scores of 5.6 and 5.8, respectively, indicating better quality of sausages stuffed into cellulose casings than LDPE casings. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-021-05222-1.

Utilization of protein isolates from rohu (Labeo rohita) processing waste through incorporation into fish sausages; quality evaluation of the resultant paste and end product.

BACKGROUND: Fish processing waste could be valorized by recuperating the nutrients for human consumption. Employing a suitable process would address the pollution problems associated with its dumping and would contribute to food security. In this study, protein isolates obtained from rohu (Labeo rohita) processing waste through the pH shift process (pH 13.0) were valorized through incorporation into pangasius (Pangasius pangasius) mince sausages (0.0, 50, 100, 250, and 500 g kg-1 ). These sausages were analyzed for their proximate composition, and their physical and eating quality. RESULTS: Increasing the isolate content (11.57% to 16.14%) in sausages increased their protein content and whiteness values (P < 0.05). At 250 g kg-1 level, the cooking yield was maximum, and the expressible fluid content of paste was minimum. Moreover, adding rohu protein isolates in pangasius mince increased the expressible moisture and decreased its folding and gel strength values (P < 0.05). The gel strength values were highest for the sausages without isolates (2648.67 g cm). In contrast, in the sausages containing 250, 100, and 500 g kg-1 isolate, the values were determined to be 847.88, 731.21, and 611.06 g cm, respectively. Replacing pangasius mince with rohu protein isolates had a non-significant effect on the sensory attributes of the sausages. CONCLUSION: Replacing pangasius mince with rohu protein isolates at 250 g kg-1 resulted in superior quality sausages compared with other levels tested. Incorporating rohu protein isolates in fish sausages improved the nutritional value without significantly reducing their eating quality. The findings of this study indicate promising potential for developing nutrient-rich foods using fish protein isolates. © 2021 Society of Chemical Industry.

Significance of nanoparticle's radius, heat flux due to concentration gradient, and mass flux due to temperature gradient: The case of Water conveying copper nanoparticles.

The performance of copper selenide and effectiveness of chemical catalytic reactors are dependent on an inclined magnetic field, the nature of the chemical reaction, introduction of space heat source, changes in both distributions of temperature and concentration of nanofluids. This report presents the significance of increasing radius of nanoparticles, energy flux due to the concentration gradient, and mass flux due to the temperature gradient in the dynamics of the fluid subject to inclined magnetic strength is presented. The non-dimensionalization and parameterization of the dimensional governing equation were obtained by introducing suitable similarity variables. Thereafter, the numerical solutions were obtained through shooting techniques together with 4th order Runge-Kutta Scheme and MATLAB in-built bvp4c package. It was concluded that at all the levels of energy flux due to concentration gradient, reduction in the viscosity of water-based nanofluid due to a higher radius of copper nanoparticles causes an enhancement of the velocity. The emergence of both energy flux and mass flux due to gradients in concentration and temperature affect the distribution of temperature and concentration at the free stream.

Design, synthesis, characterization and in vitro, in vivo and in silico antimicrobial and antiinflammatory activities of a new series of sulphonamide and carbamate derivatives of a nebivolol intermediate.

A series of new sulphonamide and carbamate derivatives of Nebivolol drug intermediate (5) were designed and synthesized by reacting various biopotent sulphonylchlorides and chloroformates. The synthesized compounds are structurally characterized by spectral (IR, 1H & 13C NMR and mass) and screened for their in vitro antimicrobial activity against four bacterial and three fungal strains, in vitro and in vivo antiinflammatory activity against LPS-induced inflammation in RAW 264.7, in vitro COX-1 and COX-2 inhibition potentiality, antagonistic profiles of carrageenan induced paw edema and cotton pellet induced granuloma in rat. Further, the compounds were screened for their antimicrobial and antiinflammatory activity against DNA gyrase A, COX-1 and COX-2 by using molecular docking approach. The bioactivity and toxicity risks were analysed through Molecular Operating Environment. The results revealed that the compounds 8b, 8c, 8d, 8e, 8f, 8g and 9a exhibited the most promising antimicrobial activity against all the bacterial and fungal strains tested when compared with the standard drugs streptomycin and fluconazole. In view of in antiinflammatory activity, the compounds, 8b, 8c, 8d, 8e, 8f, 8g and 9a have shown potent antiinflammatory activity by inhibiting the LPS-induced inflammation in RAW 264.7 cell line, concentration dependent inhibition of COX-1 and COX-2, dose response dependent antagonism of carrageenan induced paw edema and granuloma tissue in rat. Molecular docking, ADMET and QSAR studies predicted that the recorded in silico profiles are in strong correlation with in vitro and in vivo antimicrobial and antiinflammatory results. In addition, the elevated toxicology risks of the title compounds are identified with in the potential limits of drug candidates. Hence, it is suggested that the synthesized derivatives will stand as the promising antimicrobial and anti-inflammatory drug candidates in future.

Bidirectional interaction of airway epithelial remodeling and inflammation in asthma.

Asthma is a chronic disease of the airways that has long been viewed predominately as an inflammatory condition. Accordingly, current therapeutic interventions focus primarily on resolving inflammation. However, the mainstay of asthma therapy neither fully improves lung function nor prevents disease exacerbations, suggesting involvement of other factors. An emerging concept now holds that airway remodeling, another major pathological feature of asthma, is as important as inflammation in asthma pathogenesis. Structural changes associated with asthma include disrupted epithelial integrity, subepithelial fibrosis, goblet cell hyperplasia/metaplasia, smooth muscle hypertrophy/hyperplasia, and enhanced vascularity. These alterations are hypothesized to contribute to airway hyperresponsiveness, airway obstruction, airflow limitation, and progressive decline of lung function in asthmatic individuals. Consequently, targeting inflammation alone does not suffice to provide optimal clinical benefits. Here we review asthmatic airway remodeling, focusing on airway epithelium, which is critical to maintaining a healthy respiratory system, and is the primary defense against inhaled irritants. In asthma, airway epithelium is both a mediator and target of inflammation, manifesting remodeling and resulting obstruction among its downstream effects. We also highlight the potential benefits of therapeutically targeting airway structural alterations. Since pathological tissue remodeling is likewise observed in other injury- and inflammation-prone tissues and organs, our discussion may have implications beyond asthma and lung disease.

Cigarette smoke downregulates Nur77 to exacerbate inflammation in chronic obstructive pulmonary disease (COPD).

Cigarette smoke (CS) contains multiple gaseous and particulate materials that can cause lung inflammation, and smoking is the major cause of chronic obstructive pulmonary disease (COPD). We sought to determine the mechanisms of how CS triggers lung inflammation. Nur77, a nuclear hormone receptor belonging to the immediate-early response gene family, controls inflammatory responses, mainly by suppressing the NF-κB signaling pathway. Because it is unknown if Nur77's anti-inflammatory role modulates COPD, we assessed if and how Nur77 expression and activity are altered in CS-induced airway inflammation. In lung tissues and bronchial epithelial cells from COPD patients, we found Nur77 was downregulated. In a murine model of CS-induced airway inflammation, CS promoted lung inflammation and also reduced Nur77 activity in wild type (WT) mice, whereas lungs of Nur77-deficient mice showed exaggerated CS-induced inflammatory responses. Our findings in in vitro studies of human airway epithelial cells complemented those in vivo data in mice, together showing that CS induced threonine-phosphorylation of Nur77, which is known to interfere with its anti-inflammatory functions. In summary, our findings point to Nur77 as an important regulator of CS-induced inflammatory responses and support the potential benefits of Nur77 activation for COPD treatment.

Glucocorticoid Receptor α Mediates Roflumilast's Ability to Restore Dexamethasone Sensitivity in COPD.

Background: Glucocorticoids are commonly prescribed to treat inflammation of the respiratory system; however, they are mostly ineffective for controlling chronic obstructive pulmonary disease (COPD)-associated inflammation. This study aimed to elucidate the molecular mechanisms responsible for such glucocorticoid inefficacy in COPD, which may be instrumental to providing better patient outcomes. Roflumilast is a selective phosphodiesterase-4 (PDE4) inhibitor with anti-inflammatory properties in severe COPD patients who have a history of exacerbations. Roflumilast has a suggested ability to mitigate glucocorticoid resistance, but the mechanism is unknown. Methods: To understand the mechanism that mediates roflumilast-induced restoration of glucocorticoid sensitivity in COPD, we tested the role of glucocorticoid receptor α (GRα). Roflumilast's effects on GRα expression and transcriptional activity were assessed in bronchial epithelial cells from COPD patients. Results: We found that both GRα expression and activity are downregulated in bronchial epithelial cells from COPD patients and that roflumilast stimulates both GRα mRNA synthesis and GRα's transcriptional activity in COPD bronchial epithelial cells. We also demonstrate that roflumilast enhances dexamethasone's ability to suppress pro-inflammatory mediator production, in a GRα-dependent manner. Discussion: Our findings highlight the significance of roflumilast-induced GRα upregulation for COPD therapeutic strategies by revealing that roflumilast restores glucocorticoid sensitivity by sustaining GRα expression.

Molecular, chemical, and structural characterization of prostaglandin A2 as a novel agonist for Nur77.

Nur77 is a transcription factor belonging to the NR4A subfamily of nuclear hormone receptors. Upon induction, Nur77 modulates the expression of its target genes and controls a variety of biological and pathophysiological processes. Prior research that revealed a structurally atypical ligand-binding domain (LBD) and failed to locate an endogenous ligand had led to a classification of Nur77 as an orphan receptor. However, several more recent studies indicate that small synthetic molecules and unsaturated fatty acids can bind to Nur77. Discovery of additional endogenous ligands will facilitate our understanding of the receptor's functions and regulatory mechanisms. Our data have identified prostaglandin A2 (PGA2), a cyclopentenone prostaglandin (PG), as such a ligand. Cyclopentenone PGs exert their biological effects primarily by forming protein adducts via the characteristic electrophilic ß-carbon(s) located in their cyclopentenone rings. Our data show that PGA2 induces Nur77 transcriptional activity by forming a covalent adduct between its endocyclic ß-carbon, C9, and Cys566 in the receptor's LBD. The importance of this endocyclic ß-carbon was substantiated by the failure of PGs without such electrophilic properties to react with Nur77. Calculated chemical properties and data from reactive molecular dynamic simulations, intrinsic reaction co-ordinate modeling, and covalent molecular docking also corroborate the selectivity of PGA2's C9 ß-carbon towards Nur77's Cys. In summary, our molecular, chemical, and structural characterization of the PGA2-Nur77 interaction provides the first evidence that PGA2 is an endogenous Nur77 agonist.

Effect of organic acid on recovery yields and characteristics of rohu (Labeo rohita) protein isolates extracted using pH shift processing.

BACKGROUND: Proteins recovery using hydrochloric acid (HCl) in acid-aided solubilization could cause greater loss in its functionality over alkali-aided solubilization. Moreover, using HCl in edible foods is also a health concern. Replacing HCl with organic acids for acid-aided solubilization could address these problems. The aim was to study the effect of organic acid (glacial acetic acid) as a replacement for HCl during pH shift processing on the characteristics and functionality of rohu (Labeo rohita) protein isolates. Rohu proteins were obtained by solubilizing at pH 3.0 and pH 11.0 using glacial acetic acid and sodium hydroxide (10 mol L-1 ). RESULTS: Results showed that solubilization at pH 11.0 gave higher protein yields (766.8 ± 2.4 g kg-1 ) compared to solubilization at pH 3.0 (735.7 ± 7.1 g kg-1 ) (P < 0.05). Isolates from acid-aided solubilization had higher whiteness and total pigment content over isolates obtained by alkali-aided solubilization. Rohu isolates recovered by alkaline solubilization showed higher water and oil holding capacity, gel strength, folding scores, foaming and emulsion capacity than acid processed isolates (P < 0.05). Solubilization of rohu proteins using glacial acetic acid produced isolates with low breaking force (149.0 g), low storage modulus (G') values and low folding test score (1.0) over the alkaline isolates (P < 0.05). CONCLUSION: Results indicated that, recovering rohu proteins using organic acid (glacial acetic acid) could produce isolates with poor functional properties, while using the organic acid to precipitate the proteins solubilized by alkali-aided processing could produce proteins with better yields and functionality. © 2019 Society of Chemical Industry.

Sulfamethoxazole removal in membrane-photocatalytic reactor system - experimentation and modelling.

In this study, the efficacy of membrane-photocatalytic reactor (MPR) in sulfamethoxazole (SMX) removal was explored at a fixed initial SMX concentration, i.e. 100 mg/L. A supported catalyst, i.e. TiO2 on granular activated carbon (GAC-TiO2), was used for MPR experiments. The SMX removal efficiency of the MPR was investigated under a range of hydraulic retention time (i.e. HRT from 51 to 152.5 min) and TiO2 catalyst dosage (55-50 mg/L). A maximum SMX removal efficiency of 83.6% was observed under 220 mg/L catalyst dosage and 80 min HRT. The increase in catalyst dosage from 55 to 550 mg/L has increased the transmembrane pressure of the reactor from 9.8 to 22.2 kPa. A multiple non-linear regression model was developed based on the experimental data and its significance was analyzed using two-way ANOVA. Based on the model, the optimal HRT and catalyst dosage for complete SMX removal (100%) were found out. The comparison of photocatalytic degradation experiments with sorption experiments conducted earlier revealed that SMX removal in the MPR was mainly by photocatalytic degradation and not by adsorption onto GAC-TiO2 catalyst. However, the performance of MPR in removing other emerging pollutants from real-time wastewaters could be explored before its field-scale application.

Zika virus modulates blood-brain barrier of brain microvascular endothelial cells.

Zika virus (ZIKV) is a mosquito-borne Flaviviruses. ZIKV is known to cause birth defect in pregnant women, especially microcephaly in the fetus. Hence, more study is required to understand the infection of Zika virus towards human brain microvascular endothelial cells (MECs). In this study, brain MECs were infected with ZIKV at MOI of 1 and 5 in vitro. The changes in barrier function and membrane permeability of ZIKV-infected brain MECs were determined using electric cell-substrate impedance sensing (ECIS) system followed by gene expression of ZIKV-infected brain MECs at 24 hours post infection using one-color gene expression microarray. The ECIS results demonstrated that ZIKV infection enhances vascular leakage by increasing cell membrane permeability via alteration of brain MECs barrier function. This was further supported by high expression of proinflammatory cytokine genes (lnc-IL6-2, TNFAIP1 and TNFAIP6), adhesion molecules (CERCAM and ESAM) and growth factor (FIGF). Overall, findings of this study revealed that ZIKV infection could alter the barrier function of brain MECs by altering adhesion molecules and inflammatory response.

Incorporating Optical Coherence Tomography in the Cataract Preoperative Armamentarium: Additional Need or Additional Burden?

PURPOSE: To determine the usefulness of preoperative optical coherence tomography (OCT) examination to detect asymptomatic macular abnormalities in patients scheduled for cataract surgery. METHODS: Design: Prospective, interventional case series. SETTING: Iladevi Cataract and Visakha Eye Center, Ahmedabad, India. STUDY POPULATION: Patients undergoing cataract surgery and intraocular lens (IOL) implantation for senile cataracts. Preoperatively no retinal/macular pathology was identified on clinical evaluation. INTERVENTION: All eyes underwent macular 5-line raster evaluation using spectral-domain OCT before and after cataract surgery (monthly for 3 months). Central subfield thickness (CST) analysis was done. OUTCOME MEASURES: The primary outcome measure was determining the incidence of asymptomatic retinal lesions on OCT examination in clinically "normal" maculas. Secondary outcome measures included documenting change in corrected distance visual acuity and OCT thickness postoperatively. RESULTS: A total of 1444 eyes were evaluated. OCT revealed asymptomatic lesions in 133 (9.21%) patients. At 3 months, all eyes showed significant median visual improvement (from 0.45 ± 0.13 logMAR to 0.06 ± 0.08 logMAR; P = .015) and insignificant median CST change (from 223.34 ± 21.1 µm to 249.12 ± 19.24 µm; P = .19). One eye showed increased vitreomacular traction (3 months). Patients with asymptomatic lesions did not have significantly worse postoperative visual outcomes at 3 months (from 0.52 ± 0.16 logMAR to 0.14 ± 0.1 logMAR; P = .12). CONCLUSION: A total of 9.21% patients with clinically normal maculas had subtle pathology detected on OCT, but this subset of patients did not have worse postoperative visual outcomes compared to eyes with normal OCT scans. Thus, a careful pre-cataract surgery fundus examination remains an essential part of the presurgical patient evaluation.

Key Functions and Therapeutic Prospects of Nur77 in Inflammation Related Lung Diseases

The transcription factor Nur77 belongs to the NR4A subfamily of nuclear hormone receptors. It features an atypical ligand-binding site that precludes canonical ligand binding, leading to the designation orphan nuclear receptor. However, recent studies show that small molecules can interact with the receptor and modulate its activity by inducing a conformational change in the Nur77 ligand-binding site. Nur77 expression and activation are rapidly induced by various physiological and pathologic stimuli. Once expressed, Nur77 initiates transcriptional activity and modulates expression of its target genes. Both in vitro and in vivo evidence shows that Nur77 dampens the immune response to proinflammatory stimuli, such as tumor necrosis factor-α, Toll-like receptor ligands, and oxidized lipids, primarily by suppressing NF-κB signaling. Although studies focusing on Nur77's role in lung pathophysiology are currently incomplete, available data support its involvement in the pathogenesis of lung diseases, including asthma, acute lung injury, and pulmonary fibrosis, and thus suggest a therapeutic potential for Nur77 activation in these diseases. This review addresses the mechanisms that control Nur77 as well as its known roles in inflammation-related lung diseases. Evidence regarding the therapeutic potential of Nur77-targeting molecules will also be presented. Although current knowledge is limited, additional research followed by clinical studies may firmly identify Nur77 as a pharmacologic target for inflammation-related lung diseases.