ITF2357 regulates NF-κB signaling pathway to protect barrier integrity in retinal pigment epithelial cells.

The robust integrity of the retinal pigment epithelium (RPE), which contributes to the outer brain retina barrier (oBRB), is compromised in several retinal degenerative and vascular disorders, including diabetic macular edema (DME). This study evaluates the role of a new generation of histone deacetylase inhibitor (HDACi), ITF2357, in regulating outer blood-retinal barrier function and investigates the underlying mechanism of action in inhibiting TNFα-induced damage to RPE integrity. Using the immortalized RPE cell line (ARPE-19), ITF2357 was found to be non-toxic between 50 nM and 5 µM concentrations. When applied as a pre-treatment in conjunction with an inflammatory cytokine, TNFα, the HDACi was safe and effective in preventing epithelial permeability by fortifying tight junction (ZO-1, -2, -3, occludin, claudin-1, -2, -3, -5, -19) and adherens junction (E-cadherin, Nectin-1) protein expression post-TNFα stress. Mechanistically, ITF2357 depicted a late action at 24 h via attenuating IKK, IκBα, and p65 phosphorylation and ameliorated the expression of IL-1ß, IL-6, and MCP-1. Also, ITF2357 delayed IκBα synthesis and turnover. The use of Bay 11-7082 and MG132 further uncovered a possible role for ITF2357 in non-canonical NF-κB activation. Overall, this study revealed the protection effects of ITF2357 by regulating the turnover of tight and adherens junction proteins and modulating NF-κB signaling pathway in the presence of an inflammatory stressor, making it a potential therapeutic application for retinal vascular diseases such as DME with compromised outer blood-retinal barrier.

Investigating the effect of wall material and pressure homogenisation on encapsulation parameters and thermal stability in chia seed oil microcapsules.

AIM: To evaluate the effect of different wall material (WM) matrices followed by homogenisation to encapsulate chia seed oil (CSO) using freeze drying technology. METHODS: CSO was encapsulated using three ratios (100/0, 50/50, and 100/0) of two WM matrices: MTS/WPC (modified tapioca starch-whey protein concentrate) and MD/WPC (maltodextrin-whey protein concentrate). The evaluation included encapsulation efficiency (EE), oxidative stability, and α-linolenic acid (ALA) retention. Homogenised microcapsules (-H) were then assessed for storage and thermal stability, along with cumulative oil release. RESULTS: The MD-WPC-H 50/50 microcapsules had superior EE (97.32%), higher ALA retention (60.2%), storage stability (up to 30 days), higher thermal stability (up to 700 °C), and desirable oil release in simulated condition. CONCLUSION: Selecting suitable WM and homogenisation is key for improving EE, storage, thermal stability, and targeted release. The CSO microcapsule can serve as a functional ingredient to improve the quality of diverse food products.

Pathophysiology, diagnosis, and herbal medicine-based therapeutic implication of rheumatoid arthritis: an overview.

Rheumatoid arthritis (RA) stands as an autoimmune disorder characterized by chronic joint inflammation, resulting in profound physiological alterations within the body. Affecting approximately 0.4-1.3% of the global population, this condition poses significant challenges as current therapeutic approaches primarily offer symptomatic relief, with the prospect of complete recovery remaining elusive. This review delves into the contemporary advancements in understanding the pathophysiology, diagnosis, and the therapeutic potential of herbal medicine in managing RA. Notably, early diagnosis during the initial stages emerges as the pivotal determinant for successful recovery post-treatment. Utilizing tools such as Magnetic Resonance Imaging (MRI), anti-citrullinated peptide antibody markers, and radiography proves crucial in pinpointing the diagnosis of RA with precision. Unveiling the intricate pathophysiological mechanisms of RA has paved the way for innovative therapeutic interventions, incorporating plant extracts and isolated phytoconstituents. In the realm of pharmacological therapy for RA, specific disease-modifying antirheumatic drugs have showcased commendable efficacy. However, this conventional approach is not without its drawbacks, as it is often associated with various side effects. The integration of methodological strategies, encompassing both pharmacological and plant-based herbal therapies, presents a promising avenue for achieving substantive recovery. This integrated approach not only addresses the symptoms but also strives to tackle the underlying causes of RA, fostering a more comprehensive and sustainable path towards healing.

Coral red beads and arthritis.

We report a patient presenting with cutaneous papulonodular lesions associated with painful stiff joints. Histopathological examination showed positivity for CD68 and CD45. There was no atypia.

Stability enhancement of beetroot betalains through copigmentation.

BACKGROUND: Like other natural pigments, betalains have a stability problem. Copigmentation can be explored to address this issue. In this study, black carrot anthocyanins were used for the first time as copigment with betalains so that copigmented betalains with enhanced stability could be developed to withstand deteriorative processing and storage conditions. RESULTS: Increase in hyperchromic and bathochromic shift with subsequent increase in black carrot anthocyanin extract (0.250 g L-1 ) addition from 0.2 to 1.0 mL L-1 was observed in native betalain pigments from 0.28 to 1.90 and 538 nm to 564 nm, respectively. For maximum recorded bathochromic shift, 0.8 mL L-1 addition of copigment was optimized. Copigmented betalain pigment showed better stability in comparison with native pigment, when exposed to light, temperature more than 60 °C and ≥1.0 g L-1 NaCl. At constant incubation time (3 h), copigmented betalains degraded up to 20.79-41.43% whereas the non-copigmented counterpart degraded up to 83.49-86.86% at 60, 75 and 90 °C, respectively. Lower rate constant (k) and enhanced activation energy (Ea ) showed higher thermostability of copigmented betalains. With constant light exposure, the half-life value of betalains was 145.2 h, which increased approximately twofold (274.08 h) after copigmentation. The t1/2 of betalain pigment at 10%, 15% and 18% salt addition was 81.12, 75.36 and 83.52 h, which increased to 186.96, 226.56 and 152.88 h after copigmentation. CONCLUSION: These findings support that black carrot anthocyanin is a potential and compatible copigment for water-soluble betalain pigment that enhances stability of betalains under extreme processing conditions. © 2022 Society of Chemical Industry.

Real-time confirmation of tracheal decompression.

AIMS: The primary objective was to highlight the role of intraoperative bronchoscopic guidance during the management of central airway obstruction. MATERIALS & METHODS: A 6-month-old child presented with recurrent chest infections due to innominate artery compression of distal trachea. Aortopexy was performed under real-time bronchoscopic guidance. RESULTS: Intraoperative bronchoscopic guidance helped in confirm a successful release of the central airway obstruction. DISCUSSION: When operations similar to aortopexy are performed for release of airway obstructions, intraoperative bronchoscopic guidance is a valuable tool for confirming a successful outcome. CONCLUSION: The successful surgical management of central airway obstruction due to an innominate artery compression of the distal trachea under real-time bronchoscopic guidance in a 6-month-old child is described.

Evaluation of Cellulolytic Enzyme-Assisted Microwave Extraction of Punica granatum Peel Phenolics and Antioxidant Activity.

Conventional techniques for phenolics extraction from pomegranate (Punica granatum) peel (PP) have several insufficiencies like longer time duration, bioactive degradation, excess use of harmful chemicals and solvents. In the present study, we established the synergistic use of two non-conventional extraction strategies i.e., enzyme-assisted extraction (EAE) using a cellulolytic enzyme preparation (Viscozyme) followed by microwave-assisted extraction (MAE) for efficient recovery of phenolics from PP. This optimized method was individually compared with EAE, MAE, and conventional solvent extraction (CSE) methods for recovering PP phenolics with maximum antioxidant activity (AOA). Extracts were analyzed for AOA using ferric reducing antioxidant power (FRAP) and cupric reducing AOA (CUPRAC) methods. Response surface methodology (RSM), was used as an optimization tool to achieve maximum yield of phenolics and with highest AOA at power 443.5 W, time 131.0 min, and solvent-to-solid ratio 23.6:1. The predicted values for maximum phenolics and AOA obtained through RSM were 305 mg GAE/g, 1788 µmol TE/g (FRAP) and 2641 µmol TE/g (CUPRAC), respectively. Phenolic contents of only 94.6, 165.46, and 197.6 mg GAE/g were achieved through CSE, EAE and MAE, respectively. Here we substantiate the auxiliary role of Viscozyme and microwave treatment in achieving high phenolic content and AOA from PPs. Phenolic rich extracts are known to act as multi-target ligands that inhibit various enzymes involved in diseases like Alzheimer's, Parkinson's, and diabetes mellitus. The extract can be commercially exploited for the development of functional foods, supplements, and natural preservatives.

Effect of high-pressure microfluidization on nutritional quality of carrot (Daucus carota L.) juice.

In this study, the effect of high-pressure microfluidization on the colour and nutritional qualities of the orange carrot juice was investigated. The juice was processed at three different pressures (34.47 MPa, 68.95 MPa and 103.42 MPa) with three different passes (1, 2 and 3 passes). After that, total phenolic content (TPC), antioxidant activity, carotenoids, color properties, and total soluble solids content of the processed carrot juice were evaluated. As a result, no specific trends in TPC and antioxidant activity of the juice were observed through the variations of processing conditions. However, microfluidization significantly (p < 0.05) improved the carotenoids content in carrot juice. With increasing number of pass, concentrations of ß-carotene and lutein had increased significantly. Similarly, increasing process pressure initially increased carotenoid content significantly (up to 68.95 MPa), further increase pressure to 103.42 MPa did not cause significant changes in carotenoid concentration. Furthermore, color properties such as lightness, redness, yellowness, and chroma value were reduced significantly with the increase of pressure and the number of passes. The results indicated that high-pressure microfluidization could be used as a novel alternative nonthermal technology to heat pasteurization to improve the color and nutritional qualities in orange carrot juice, resulting in a desirable, high-quality juice for consumers.

Lichen Planus Pemphigoides Mimicking Toxic Epidermal Necrolysis.

Lichen planus pemphigoides (LPP) is an immunobullous disorder characterized by a combination of lesions resembling bullous pemphigoid and lichen planus (LP). Immunofluorescence studies typically show linear deposition of IgG and C3 along the basement membrane zone and circulating antibodies to the hemidesmosome protein BP180 also known as type XVII collagen. It is now recognized that drug-induced linear IgA disease may present with lesions mimicking toxic epidermal necrolysis (TEN). However, to date, there have been no reported cases of LPP presenting with TEN-like lesions. This report describes a 70-year-old woman with LPP who presented with extensive erosions mimicking TEN. This case also highlights the need to consider important etiologies such as drug-induced and paraneoplastic LPP.

Targeted metabolite profiling to gain chemometric insight into Indian pomegranate cultivars and elite germplasm.

BACKGROUND: Pomegranate fruit is an excellent source of bioactive polyphenolics, known to contribute significantly to human health. India is the largest producer of pomegranate in the world and produces the finest quality fruit with highly desirable consumer traits such as soft seeds, low acidity, and attractive fruit and aril color. Knowledge of the extent of variation in key metabolites (sugars, organic acids, phenolics, and anthocyanins) is key to selecting superior genotypes for germplasm improvement. Relevant information with respect to Indian genotypes is scarce. The present study therefore aims to evaluate quantitatively important metabolites in some cultivars and elite germplasm of pomegranate in India. RESULTS: Identification and quantification of primary and secondary metabolites such as sugars, organic acids, vitamin C, polyphenolics, and anthocyanins were conducted using a liquid chromatography - mass spectrometry (LC-MS) platform. Fructose and citric acid were the predominant sugar and organic acid, respectively. Wild genotypes had significantly higher concentrations of organic acids, antioxidant activity, and phenolics, namely punicalagin, ellagic acid, sinapic, and ferulic acid. CONCLUSION: Cyanidin and delphinidin derivatives of anthocyanins were more abundant in red aril commercial genotypes. Results suggest that wild-sour accessions represent a rich source of polyphenolics that can be utilized in future breeding programs to breed healthier varieties, food supplements, and pharmaceutical products. © 2019 Society of Chemical Industry.

Potentiality of freeze-thaw treatment to produce soft textured aonla (Emblica officinalis) candies.

Aonla, due to its astringency, is converted into various processed products. Candy is the most popular of among them. Commercially available aonla candies in India are hard in texture. However, soft textured candies are preferred more over harder ones. Hence, study was undertaken to produce soft textured candies. Whole fruits and fruit segments were blanched in boiled water, frozen in domestic freezer for 12 h and thawed at room temperature (15-20 °C). Fresh, blanched, frozen and thawed samples were subjected to textural analysis. Some of the blanched and thawed segments were used to prepare candies and subjected to textural analysis. Results indicated that force-deformation behavior of all samples differed significantly. Fresh, blanched, thawed and frozen segments required 14.39, 0.84, 0.22 and 0.18 N force, respectively to compress them till 1 mm deformation. Similarly, peak force (5 mm deformation) was maximum in fresh segments (172.25 N) followed by blanched (8.77 N), frozen (1.06 N) and thawed (0.85 N). Peak force values for control and soft candies were 13.14 and 6.86 N, respectively. Based on results, it was found that freeze-thaw treatment significantly reduced the firmness of segments and produced soft textured candies.

Optimization and comparison of non-conventional extraction technologies for Citrus paradisi L. peels: a valorization approach.

The phenolics from grapefruit peel were obtained by ultrasound assisted extraction (UAE) and enzyme-assisted extraction (EAE). Extraction parameters were optimized using response surface methodology to maximize the yield of total phenolic content (TPC) and total flavonoid content (TFC). The optimized extracts from UAE and EAE were then compared with conventional solvent extraction for their TPC, TFC, antioxidant activity and phenolic composition. The best optimized conditions for UAE was obtained at 33.12 min extraction time, 71.11% amplitude and a solvent-solid (SS) ratio of 39.63 mL/g. The optimized parameters for EAE were 4.81 h extraction time, 0.9% enzyme concentration and 40 mL/g SS ratio. Similar values of experimental and predicted TPC and TFC at optimized conditions indicates the suitability of the quadratic model in optimizing the extraction parameters. Further characterization of extracts suggested EAE as most efficient process in extracting bioactive compounds.

Valorisation of black carrot pomace: microwave assisted extraction of bioactive phytoceuticals and antioxidant activity using Box-Behnken design.

The present study compares three methods viz. microwave assisted extraction (MAE), ultrasonic-assisted extraction (UAE) and conventional solvent extraction (CSE) for extraction of phenolic compounds from black carrot pomace (BCP). BCP is the major by-product generated during processing and poses big disposal problem. Box-Behnken design using response surface methodology was employed to investigate and optimize the MAE of phenolics, antioxidant activity and colour density from BCP. The conditions for maximum recovery of polyphenolics were: microwave power (348.07 W), extraction time (9.8 min), solvent-solid ratio (19.3 mL/g) and ethanol concentration (19.8%). Under these conditions, the extract contained total phenolic content of 264.9 ± 10.02 mg gallic acid equivalents (GAE)/100 mL, antioxidant capacity (AOC) of 13.14 ± 1.05 µmol Trolox equivalents (TE)/mL and colour density of 68.63 ± 5.40 units. The total anthocyanin content at optimized condition was 753.40 ± 31.6 mg/L with low % polymeric colour of 7.40 ± 0.42. At optimized conditions, MAE yielded higher colour density (68.63 ± 5.40), polyphenolic content (264.9 ± 10.025 mg GAE/100 mL) and AOC (13.14 ± 1.05 µmol TE/mL) in a short time as compared to UAE and CSE. Overall results clearly indicate that MAE is the best suited method for extraction in comparison to UAE and CSE. The phenolic rich extract can be used as an effective functional ingredient in foods.

Phytonutrient composition, antioxidant activity and acceptability of muffins incorporated with red capsicum pomace powder.

Enzymatic liquefaction (EL) ensures fast extraction and enhanced recovery of bioactives from red capsicum along with reduced degradation of these compounds remained in the pomace. Hence, red capsicum pomace obtained as byproduct after EL was freeze dried to produce capsicum pomace powder (CP). CP had almost 80% of bioactives (total carotenoids 91.23 ± 2.35 mg/100 g) and antioxidant activity (DPPH 1.61 ± 0.12 µmol TE/g) compared to fresh pomace. CP was further used to develop muffins. Different concentrations (2-10%) of CP were mixed in wheat flour for preparation of muffins. Wheat flour was fortified with CP at different levels (2-10%) and subsequently, effect of CP fortification on height, texture, bioactives and sensory quality of muffins was observed. CP fortification improved the quality in terms of color, flavor and texture. During storage, hardness values (34.42-32.56 N) showed decreasing trend with increase in CP content. Overall, 6% CP fortification was found most acceptable without causing significant change in porosity and crust uniformity of fortified muffins. Thus, present study demonstrated that fortification of muffins with 6% CP as functional ingredient offers an opportunity to develop quality muffins with enhanced antioxidant activity (DPPH 13.04 ± 0.02 µmol TE/g) and total carotenoids (3.46 ± 2.41 mg/100 g).

Transitory cystic cavities in the developing mammalian brain - normal or anomalous?

Transitory cavities associated with the ventricular system represent probably one of the most unique features in the developing mammalian brain. In rodents, the cavities exist transiently in the developing brain and do not appear to be associated with any pathological events. Among the various cavities, the pyramidal-shaped cavum septum pellucidum (CSP) located beneath the corpus callosum and between the lateral ventricles is most well defined. In addition to the CSP are the bilateral subependymal cysts that are consistently associated with the third and fourth ventricles as well as the aqueduct. The cavities/cysts contain a large number of amoeboid microglia expressing surface receptors and hydrolytic enzymes common to tissue macrophages. The significance of these cavities in the developing brain remains a conjecture. Firstly, the cavity walls are free of an apparent epithelial lining; hence, it is speculated that the cavities that appear to communicate with the widened neighboring interstitial tissue spaces may have resulted from physical traction due to the rapid growth of the perinatal brain. Secondly, the cavities contain prominent clusters of amoeboid microglia that may be involved in clearing the debris of degenerating axons and cells resulting from the early brain tissue remodeling. With the increase in brain tissue compactness following the beginning of myelination in the second postnatal week, all cavities are obliterated; concomitantly, the number of amoeboid microglia in them diminishes and all this might signal further maturation of the brain.

Factors influencing the uptake of neonatal bereavement support services - Findings from two tertiary neonatal centres in the UK.

BACKGROUND: Research on perinatal bereavement services is limited. The aim of the study was to compare the uptake of bereavement support services between two tertiary neonatal units (NNU), and to investigate influencing factors. METHOD: The medical and bereavement records of all neonatal deaths were studied from January 2006 to December 2011. Data collected included parent and baby characteristics, mode of death, consent for autopsy and bereavement follow-up. The categorical data were compared by chi-square or Fisher's exact test and continuous data by Wilcoxon signed-rank test; a multivariable regression analysis was performed using STATA 12.0. RESULTS: The neonatal deaths of 297 babies (182 in NNU1 and 115 in NNU2) with full datasets were analysed. Baby characteristics were similar between units except for lower median gestational age in NNU1 (p = 0.03). Significantly more NNU1 parents were non-Caucasian (p < 0.01), from lower socio-economic status (p = 0.01) and had previous stillbirth/miscarriage (p = 0.03). More babies had care withdrawn in NNU2 (p < 0.01). A significantly higher proportion of parents from NNU1 (61 %) attended bereavement follow-up compared to NNU2 (34 %; p < 0.01). On multivariable analysis, significantly more parents who were married or co-habiting (p = 0.02) and consented for an autopsy (p = 0.01) attended bereavement services. CONCLUSION: Uptake of bereavement services varied between the two NNUs, which could be due to differences in the ethnic and socio-economic mix of the population. Significantly more parents who were married or co-habiting, or consented for autopsy, attended bereavement follow up services.

MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction.

Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40 mM glucose) and at various time intervals (6, 12, 24 and 48 h). miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a) to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.

Vascular changes in the developing rat retina in response to hypoxia.

This study was carried out to investigate the roles of tight junction (TJ) proteins and other factors in the increased permeability of the blood retinal barrier (BRB) affecting the immature neonatal retina following a hypoxic insult. The expression of endothelial TJ proteins such as claudin-5, occludin and zonula occludens-1 (ZO-1) and endothelial cell specific molecule-1 (ESM-1), and associated structural changes in the blood vessels were analyzed in the retinas of 1-day-old Wistar rats subjected to hypoxia for 2 h and subsequently sacrificed at different time points ranging from 3 h to 14 d. The mRNA and protein expression of claudin-5, occludin & ZO-1 was found to be reduced in the hypoxic retina, although, at the ultrastructural level, the TJ between the endothelial cells and retinal pigment epithelial cells appeared to be intact. Following the hypoxic insult vascular endothelial cells frequently showed presence of cytoplasmic vacuoles, vacuolated mitochondria and multivesicular aggregations projecting into the lumen of the capillaries. The expression of ESM-1 in the immature retinas was found to be increased following hypoxic exposure. The structural and molecular changes in the hypoxic neonatal retinas were consistent with a hypoxia induced impairment of the BRB. Hypoxia reduced the expression of TJ proteins in the neonatal retina, but the role of increased ESM-1 expression in this process warrants further investigation.