Vasoactive Intestinal Peptide Receptor, CRTH2, Antagonist Treatment Improves Eosinophil and Mast Cell-Mediated Esophageal Remodeling and Motility Dysfunction in Eosinophilic Esophagitis.

BACKGROUND AND AIMS: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. METHODS: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. RESULTS: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. CONCLUSIONS: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.

Evaluating the Diagnostic Efficacy of 99mTc-Methionine Single-Photon Emission Computed Tomography-Computed Tomography: A Head-to-Head Comparison with 11C-Methionine Positron Emission Tomography-Magnetic Resonance Imaging in Glioma Patients.

Background: Amino acid positron emission tomography (PET) imaging plays a significant role in the diagnosis of gliomas and in differentiating tumor recurrence from necrosis. In this study, the authors have evaluated the diagnostic efficacy of [99mTc]Tc-methionine single-photon emission computed tomography-computed tomography (SPECT-CT) in comparison with [11C]methionine PET-magnetic resonance imaging (MRI) in delineating tumors. Methods: Thirty-one (primary: 16 and postoperative: 15) patients of confirmed (either MRI or histopathological proven) glioma underwent both [99mTc]Tc-methionine SPECT-CT and [11C]methionine PET-MRI. A comparative analysis was performed between SPECT, PET, and MR images to calculate the concordance between the modalities and to evaluate the diagnostic efficacy of the [99mTc]Tc-methionine SPECT. Results: [99mTc]Tc-methionine SPECT showed comparable uptake in the tumor lesions in comparison to [11C]methionine PET. A significant and strong positive correlation was observed between the volume of tumor (Vt) in PET and Vt MR (p < 0.004). Likewise, a significant and strong positive correlation was found between Vt SPECT and Vt MR. [99mTc]-methionine has a sensitivity and specificity of 91% and 75%, respectively, compared with 82% and 100% for [11C]methionine in postoperative cases to differentiate the tumor recurrence from necrosis. The sensitivity and specificity of [99mTc]Tc-methionine was 92% and 100%, respectively, compared with 92% and 67% for [11C]methionine in primary tumors. Conclusion: [99mTc]Tc-methionine SPECT-CT is as equally good as [11C]methionine for diagnosing and differentiating it from necrosis especially in high-grade glioma.

An Insight into the Effect of Schiff Base and their d and f Block Metal Complexes on Various Cancer Cell Lines as Anticancer Agents: A Review.

Over the last few decades, an alarming rise in the percentage of individuals with cancer and those with multi-resistant illnesses has forced researchers to explore possibilities for novel therapeutic approaches. Numerous medications currently exist to treat various disorders, and the development of small molecules as anticancer agents has considerable potential. However, the widespread prevalence of resistance to multiple drugs in cancer indicates that it is necessary to discover novel and promising compounds with ideal characteristics that could overcome the multidrug resistance issue. The utilisation of metallo-drugs has served as a productive anticancer chemotherapeutic method, and this approach may be implemented for combating multi-resistant tumours more successfully. Schiff bases have been receiving a lot of attention as a group of compounds due to their adaptable metal chelating abilities, innate biologic properties, and versatility to tweak the structure to optimise it for a specific biological purpose. The biological relevance of Schiff base and related complexes, notably their anticancer effects, has increased in their popularity as bio-inorganic chemistry has progressed. As a result of learning about Schiff bases antitumor efficacy against multiple cancer cell lines and their complexes, researchers are motivated to develop novel, side-effect-free anticancer treatments. According to study reports from the past ten years, we are still seeking a powerful anticancer contender. This study highlights the potential of Schiff bases, a broad class of chemical molecules, as potent anticancer agents. In combination with other anticancer strategies, they enhance the efficacy of treatment by elevating the cytotoxicity of chemotherapy, surmounting drug resistance, and promoting targeted therapy. Schiff bases also cause cancer cell DNA repair, improve immunotherapy, prevent angiogenesis, cause apoptosis, and lessen the side effects of chemotherapy. The present review explores the development of potential Schiff base and their d and f block metal complexes as anticancer agents against various cancer cell lines.

Nanoemulsion potentiates the anti-cancer activity of Myricetin by effective inhibition of PI3K/AKT/mTOR pathway in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is a heterogeneous tumor with a poor prognosis and high metastatic potential, resulting in poor clinical outcomes, necessitating investigation to devise effective therapeutic strategies. Multiple studies have substantiated the anti-cancer properties of the naturally occurring flavonoid "Myricetin" in various malignancies. However, the therapeutic application of Myricetin is impeded by its poor water solubility and low oral bioavailability. To overcome this limitation, we aimed to develop nanoemulsion of Myricetin (Myr-NE) and evaluate its advantage over Myricetin alone in TNBC cells. The nanoemulsion was formulated using Capryol 90 (oil), Tween 20 (surfactant), and Transcutol HP (co-surfactant). The optimized nano-formulation underwent an evaluation to determine its size, zeta potential, morphology, stability, drug encapsulation efficiency, and in vitro release properties. The anti-cancer activity of Myr-NE was further studied to examine its distinct impact on intracellular drug uptake, cell-viability, anti-tumor signaling, oxidative stress, clonogenicity, and cell death, compared with Myricetin alone in MDA-MB-231 (TNBC) cells. The in vitro drug release and intracellular drug uptake of Myricetin was significantly increased in Myr-NE formulation as compared to Myricetin alone. Moreover, Myr-NE exhibited significant inhibition of cell proliferation, clonogenicity, and increased apoptosis with ~ 2.5-fold lower IC50 as compared to Myricetin. Mechanistic investigation revealed that nanoemulsion augmented the anti-cancer efficacy of Myricetin, most likely by inhibiting the PI3K/AKT/mTOR pathway, eventually leading to enhanced cell death in TNBC cells. The study provides substantial experimental evidence to support the notion that the Myr-NE formulation has the potential to be an effective therapeutic drug for TNBC treatment.

Comparative study of functional outcomes of arthroscopic anterior cruciate ligament reconstruction using anteromedial portal and translateral all-inside technique.

Background: Anterior Cruciate Ligament (ACL) injuries are common in the active population of the Armed Forces. Symptomatic instability prompts individuals to seek a cure or a sheltered appointment. Despite the increasing numbers of ACL reconstructions performed, the outcomes have not been so spectacular with only a meager percentage of our patients returning to preinjury levels of activity. With the premise that an all-inside ACL reconstruction is likely to result in better functional outcomes, the aim of this study was to compare the short-term functional outcomes of a large consecutive series of patients undergoing ACL reconstruction using the translateral all-inside ACL reconstruction technique (AI) and standard anteromedial portal technique (AM) with a minimum follow-up of one year. Methods: A total of 240 patients with isolated ACL tear underwent ACL reconstruction via the AI or AM technique. Their preoperative and postoperative scores were compared to look for any significant differences in functional outcomes. Results: The two groups were matched for age, BMI, mechanism of injury, and interval from injury to surgery. There was no difference in their preoperative scores. Postoperatively, although there were significant improvements across both groups, there was no significant difference between the groups at any point of time. Conclusion: The AI technique has garnered interest in recent literature in addressing ACL injuries. This study found no discernible benefit of the AI technique when compared to the AM technique in terms of functionality following an ACL reconstruction at any point of time up to 1 year following surgery.

Preclinical and Clinical Use of Indigenously Developed 99mTc-Diethylenetriaminepentaacetic Acid-Bis-Methionine: l-Type Amino Acid Transporter 1-Targeted Single Photon Emission Computed Tomography Radiotracer for Glioma Management.

A new era in tumor classification, diagnosis, and prognostic evaluation has begun as a consequence of recent developments in the molecular and genetic characterization of central nervous system tumors. In this newly emerging era, molecular imaging modalities are essential for preoperative diagnosis, surgical planning, targeted treatment, and post-therapy evaluation of gliomas. The radiotracers are able to identify brain tumors, distinguish between low- and high-grade lesions, confirm a patient's eligibility for theranostics, and assess post-radiation alterations. We previously synthesized and reported the novel l-type amino acid transporter 1 (LAT-1)-targeted amino acid derivative in light of the use of amino acid derivatives in imaging technologies. Further, we have developed a single vial ready to label Tc-lyophilized kit preparations of diethylenetriaminepentaacetic acid-bis-methionine [DTPA-bis(Met)], also referred to as methionine-diethylenetriaminepentaacetic acid-methionine (MDM) and evaluated its imaging potential in numerous clinical studies. This review summarizes our previous publications on 99mTc-DTPA-bis(Met) in different clinical studies such as detection of breast cancer, as a prognostic marker, in detection of recurrent/residual gliomas, for differentiation of recurrent/residual gliomas from radiation necrosis, and for comparison of 99mTc-DTPA-bis(Met) with 11C-L-methionine (11C-MET), with relevant literature on imaging modalities in glioma management.

Allergen-induced NLRP3/caspase1/IL-18 signaling initiate eosinophilic esophagitis and respective inhibitors protect disease pathogenesis.

The current report describes a stepwise mechanistic pathway of NLRP3/caspase1/IL-18-regulated immune responses operational in eosinophilic esophagitis (EoE). We show that esophageal epithelial cells and macrophage-derived NLRP3 regulated IL-18 initiate the disease and induced IL-5 facilitates eosinophil growth and survival. We also found that A. fumigatus-exposed IL-18-/- mice or IL-18-neutralized mice are protected from EoE induction. Most importantly, we present that intravascular rIL-18 delivery to ΔdblGATA mice and CD2-IL-5 mice show the development of EoE characteristics feature like degranulated and intraepithelial eosinophils, basal cell hyperplasia, remodeling and fibrosis. Similarly, we show an induced NLRP3-caspase1-regulated IL-18 pathway is also operational in human EoE. Lastly, we present the evidence that inhibitors of NLRP3 and caspase-1 (MCC950, BHB, and VX-765) protect A. fumigatus- and corn-extract-induced EoE pathogenesis. In conclusion, the current study provides a new understanding by implicating NLRP3/caspase1-regulated IL-18 pathway in EoE pathogenesis. The study has the clinical significance and novel therapeutic strategy, which depletes only IL-18-responsive pathogenic eosinophils, not naïve IL-5-generated eosinophils critical for maintaining innate immunity.

Percutaneous Suspensory Stabilization of Chronic Distal Radioulnar Joint (DRUJ) Dislocation Using an Adjustable Loop Endobutton Construct: Case Report.

Chronic distal radioulnar joint (DRUJ) dislocation has been treated historically with complex osteotomies and reconstructive procedures, often resulting in intractable stiffness and loss of function. It is desirable to use a technique of fixation that will not only restore the wrist biomechanics but also be cosmetically appealing to the individual. We present a novel technique of reduction and fixation of a chronically dislocated DRUJ in a 26-year-old male using a minimally invasive approach, with successful restoration of DRUJ function and no postoperative complications.

Radiolabelled folate micellar carriers as proposed diagnostic aid for CNS tumors by nasal route.

Glioma refers to the most atypical variant of the malignant central nervous system tumors posturing massive challenge to the research fraternity owing to the flimsy improvement in the patient survival rate over the past years. The aim of the proposed work was developing a diagnostic aid for brain tumors, which could be administered via the non-invasive intranasal route. Since overexpression of folate receptors in the central nervous system tumors is 500 times more than the normal healthy cells, we aimed at fabricating a radiolabeled folate encapsulated micellar delivery system to be given via the nasal route. Folate conjugated bifunctional chelating agent was synthesized, radiolabeled with 99mTc, and encapsulated in a micellar carrier. The fabricated micelles were further evaluated for in vivo nasal toxicity in rats and the same were found safe for intranasal administration. The fabricated micelles owing to their nano size, mucoadhesive nature, and enhanced permeation were observed to have a higher uptake into the brain (around 16% in 4 h) than as compared to the radiolabeled conjugated folate solution when studied for in vivo biodistribution in mice. Single-photon emission computerized tomography imaging performed in higher animals upon intranasal administration of the micellar formulation revealed enhanced uptake of the micelles into the animal brain. It is believed that the aforementioned formulation can be of a great diagnostic value in the detection of not only brain tumors but also other folate expressing cancers such as cervical, breast, and lungs as the system is fast, non-toxic, accurate, non-invasive, and simple.

Percutaneous Suspensory Stabilization of Chronic Distal Radioulnar Joint (DRUJ) Dislocation Using an Adjustable Loop Endobutton Construct: Case Report / Fixação suspensiva percutânea de luxação crônica da articulação radioulnar distal (ARUD) usando um dispositivo de endobutton de laço ajustável: Relato de caso

Abstract Chronic distal radioulnar joint (DRUJ) dislocation has been treated historically with complex osteotomies and reconstructive procedures, often resulting in intractable stiffness and loss of function. It is desirable to use a technique of fixation that will not only restore the wrist biomechanics but also be cosmetically appealing to the individual. We present a novel technique of reduction and fixation of a chronically dislocated DRUJ in a 26-year-old male using a minimally invasive approach, with successful restoration of DRUJ function and no postoperative complications.

Resumo Luxação crônica da articulação radioulnar distal (ARUD) foi tratada historicamente com osteotomias complexas e procedimentos reconstrutivos, geralmente resultando em rigidez intratável e perda de função. É desejável usar uma técnica de fixação que não apenas restaure a biomecânica do punho, mas também seja esteticamente atraente para o indivíduo. Apresentamos uma nova técnica de redução e fixação de uma ARUD deslocada cronicamente em um homem de 26 anos, usando uma abordagem minimamente invasiva, com restauração bem-sucedida da função da ARUD e sem complicações pós-operatórias.

Targeting of rainwater harvesting structures using geospatial tools and analytical hierarchy process (AHP) in the semi-arid region of Rajasthan (India).

Burgeoning population growth and subsequent demand for freshwater, besides competition among irrigation, domestic, and industrial sectors, coupled with a changing climate, have necessitated prudent and effective management of water resources. Rainwater harvesting (RWH) is considered one of the most effective strategies for water management. However, the location and design of RWH structures are essential for proper implementation, operation, and maintenance. An attempt has been made in this study to locate the most suitable site for RWH structure and design using one of the robust multi-criteria decision analysis techniques, viz. analytic hierarchy process, using geospatial tools in the Gambhir watershed, Rajasthan, India. High-resolution Sentinel-2A data and a digital elevation model of the Advanced Land Observation Satellite were used in this study. Five biophysical parameters, viz. land use and land cover, slope, soil texture, surface runoff, and drainage density, were considered to identify suitable locations for RWH structures. It was observed that runoff is the prime factor in determining the location of RWH structures compared to other parameters. It was revealed that 75.54 km2 (13% of the total area) was very highly suited for the construction of RWH structures, while 114.56 km2 (19%) was highly suitable. A total of 43.77 km2 (7%) of land was determined to be unsuitable for the construction of any type of RWH structure. Farm ponds, check dams, and percolation ponds were suggested for the study area. Furthermore, Boolean logic was used to target a particular type of RWH structure. The study indicated that a total of 25 farm ponds, 14 check dams, and 16 percolation ponds can be constructed at identified locations in the watershed. Water resource development maps of the watershed generated using an analytical approach would be useful for policymakers and hydrologists for targeting and implementing RWH structures in the study watershed.

Assessment of genetic diversity of the fat-tailed Dumba sheep of India by mitochondrial and microsatellite markers.

India has a centuries-old tradition of sheep production and breeding that accomplish economic, agricultural, and religious roles. In addition to the 44 registered sheep breeds, there is a fat-tailed sheep population referred to as Dumba. This study evaluated genetic variation in Dumba sheep and its differentiation from other Indian sheep breeds using mitochondrial DNA and genomic microsatellite loci. Haplotype and nucleotide diversity based on mitochondrial DNA analysis revealed substantially high maternal genetic diversity in Dumba sheep. Major ovine haplogroups A and B observed in sheep populations across the globe registered their presence in the Dumba sheep. The molecular genetic analysis using microsatellite markers also showed high measures of allele (10.125 ± 0.762) and gene diversity (0.749 ± 0.029). Results correspond to the non-bottleneck population that is near mutation-drift equilibrium despite some deficiency in the number of heterozygotes (FIS = 0.043 ± 0.059). Phylogenetic clustering confirmed Dumba to be a distinct population. Results of this study endow authorities with critical information imperative for sustainable utilization and conservation of Indian fat-tailed sheep, which is considered to be an untapped genetic resource contributing to the food security, livelihood, and economic sustainability of rural households in marginal areas of the country.

IL-18-mediated neutrophil recruitment promotes acute lung injury in inflammation-mediated chronic pancreatitis.

Lung injury is the most common secondary complication of pancreatitis and pancreatic malignancy. Around 60-70% of pancreatitis-related deaths are caused by lung injury; however, there is no animal model of the inflammation-mediated progressive pulmonary pathological events that contribute to acute lung injury in chronic pancreatitis (CP). Hence, we developed an inflammation-mediated mouse model and studied the pathological events that have a critical role in promoting the pathogenesis of lung injury. Our proteomic analysis of lung tissue revealed neutrophil-associated induction of neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase enzyme, further supporting a role for neutrophils in promoting IL-18-associated lung injury. We show that neutrophils released IL-18-induced p-NF-κB along with profibrotic and oncogenic proteins like TTF1, PDX1, and SOX9 in lung tissues of a mouse model of chronic pancreatitis. We also show that neutrophil infiltration induces TGF-ß and SMAD4 and activates epithelial cells to produce other profibrotic proteins like ZO-1 and MUC2, along with the fibroblast markers FGF-1 and αSMA, that cause mesenchymal transition and accumulation of extracellular matrix collagen. Most importantly, we present evidence that IL-18 inhibition significantly alleviates CP-induced lung injury. This was further established by the finding that IL-18 gene-deficient mice showed improved lung injury by inhibition of TGF-ß and fibroblast to mesenchymal transition and reduced collagen accumulation. The present study suggests that inhibition of IL-18 may be a novel treatment for CP-associated induced acute lung injury.

Development and Characterization of Novel Chronic Eosinophilic Inflammation- Mediated Murine Model of Malignant Pancreatitis.

AIMS: Develop a novel murine models of malignant pancreatitis. BACKGROUND: Although patients with chronic pancreatitis are at a greater risk of developing pancreatic cancer, there is no definitive mouse model that currently develops chronic pancreatitis-induced pancreatic cancer. OBJECTIVE: Characterization of eosinophilic inflammation-mediated malignant pancreatitis in novel murine model. METHODS: We developed a murine model of chronic eosinophilic inflammation associated with pancreatitis that also shows characteristic features of pancreatic malignancy. The mouse received cerulein and azoxymethane via intraperitoneal administration developed pathological malignant phenotype, as well as concomitant lung inflammation. RESULTS: We discovered pathological alterations in the pancreas that were associated with chronic pancreatitis, including a buildup of eosinophilic inflammation. Eosinophil degranulation was reported nearby in the pancreas tissue sections that show acinar-to-ductal metaplasia and acinar cell atrophy, both of which are characteristic of pancreatic malignancies. Additionally, we also observed the formation of PanIN lesions after three initial doses of AOM and eight weeks of cerulein with the AOM treatment regimen. We discovered that persistent pancreatic eosinophilic inflammation linked with a pancreatic malignant phenotype contributes to pulmonary damage. The RNA seq analysis also confirmed the induction of fibro-inflammatory and oncogenic proteins in pancreas and lung tissues. Further, in the current manuscript, we now report the stepwise kinetically time-dependent cellular inflammation, genes and proteins involved in the development of pancreatitis malignancy and associated acute lung injury by analyzing the mice of 3 AOM with 3, 8, and 12 weeks of the cerulein challenged protocol regime. CONCLUSION: We first show that sustained long-term eosinophilic inflammation induces time-dependent proinflammatory, profibrotic and malignancy-associated genes that promote pancreatic malignancy and acute lung injury in mice.

A rare case of syphilitic Charcot joint involving left elbow.

Charcot arthropathy is characterized by joint dislocations, pathologic fractures, and debilitating deformities. Syphilis was believed to be the most common cause of Charcot arthropathy a century back, but now, it is one of the rare causes which get missed in the routine evaluation. We present a rare case of syphilitic Charcot joint in a middle aged, paraplegic, wheel-chaired bound male, who presented with a history of recurrent painless joint swelling. He underwent multiple surgeries on the left elbow to deal with his soft tissues and bony infections along with multiple courses of systemic high end antibiotics including anti-tubercular drugs without much benefit. He was even planned for midarm amputation. Timely opinion of dermatologist and correct interpretation of serological tests clinched the diagnosis. This case highlights a high index of suspicion and correct interpretation of serological test of syphilis is essential to diagnose tertiary syphilis. Timely management with injection benzathine penicllin resulted in life time gratifying outcome.

Occurrence of enteric viruses causing clinical diarrhea in small ruminants in northern Indian plains: a reverse transcription PCR based molecular study.

Fowlpox virus (FPV) infects chickens and turkeys giving rise to pock lesions on various body parts like combs, wattles, legs, shanks, eyes, mouth, etc. The birds, affected with FPV, also show anemia and a ruffled appearance which are clinical symptoms of reticuloendotheliosis. Interestingly, the field strains of FPV are integrated with the provirus of reticuloendotheliosis virus (REV). Due to this integration, the infected birds, upon replication of FPV, give rise to free REV virions, causing severe immunosuppression and anemia. Pox scabs, collected from the infected birds, not only show positive PCR results upon performing FPV-specific 4b core protein gene PCR but also show positive results for the PCR of REV-specific env gene and FPV-REV 5'LTR junction. Homogenized suspension of the pock lesions, upon inoculating to the chorio-allantoic membrane (CAM) of 10-day-old specific pathogen-free embryonated chicken eggs, produces characteristic pock lesions in serial passages. However, the lesions also harbor REV mRNA or free virion, which can be identified by performing REV-specific env gene PCR using REV RNA from FPV-infected CAMs. The study suggests successful replication and availability of REV mRNA and free virion alongside the FPV, although the CAM is an ill-suited medium for any retroviral (like REV) growth and replication.

Long term Th2 cytokines immunotherapy beneficial for EoE pediatric patients?

Eosinohilic esophagitis (EoE) and gastroesophageal reflux diseases (GERD) are closely related esophageal disorders, and both accumulate eosinophils in the esophagus. However, origin of both these diseases are very different. The evidence indicates that acid reflux is the main cause of GERD; whereas EoE is induced in response to food or environment allergens exposed accumulation of inflammatory cells like eosinophils, mast cells and T cell subsets. EoE is a global problem, and effect even 1 year old children to adult population. Currently, mepolizumab (anti-IL-5) neutralization therapy sdata showed reduced epithelial layer eosinophilia in EoE,1, 2 and most recently FDA approved FDA has also approved Dupixent (anti-IL4R and anti-IL-13) for EoE following Phase 3 randomized, double-blind, placebo-controlled trial. The efficacy and safety of Dupixent 300 mg weekly patients 12 year or older on limited patient number, 69% and 64% reduction in EoE symptoms from baseline compared to 32% and 41% for placebo (FDA, 2022). In this commentary, we raised few concerns to be considered on these therapies based on the significance of IL-5, IL-4 in maintaining the innate immunity of the young children are mostly effected by EoE that require long term immunotherapy of mepolizumab (anti-IL-5) or Dupixent (anti-IL4R and anti-IL-13).

Kinetic and Computational Study of Degradation of Two Azo Dyes, Metanil Yellow and Orange II, by Iron Oxide Nanoparticles Synthesized Using Hylocereus undatus.

Wastewater treatment is an unavoidable necessity and requires immediate action with the aim of saving future generations from water crises and ensuring the sustainability of clean and drinkable water. In the present work, green synthesis of iron oxide nanoparticles (IONPs) was carried out from fruit extract of Hylocereus undatus to observe its photocatalytic activity towards two azo dyes, namely, Metanil yellow and Orange II dye. IONPs served as an efficient photocatalyst for the degradation of Metanil yellow dye, and the reaction followed pseudo-first-order kinetics. The effect of the initial dye concentration, amount of photocatalyst added, and effect of pH on photocatalytic degradation of Metanil yellow and Orange II dye using IONPs was studied. The results were compiled to reveal the most effective conditions for degradation to occur. A computational study of two dyes using DFT (Density Functional Theory) calculations were also performed to calculate thermodynamic properties such as the free energy, dipole moment, HOMO-LUMO energy gap, chemical potential, global hardness, softness, global electrophilicity index, ionization potential, electron affinity, etc. These parameters were used to describe the reactivity of dye toward the active photocatalytic species responsible for the degradation of dye. Natural population analysis was also performed, and Fukui indices were also calculated to explain the possible attacking sites of dyes by active photocatalytic species.

Molecules involved in the development of Barrett's esophagus phenotype in chronic eosinophilic esophagitis.

This paper aims to investigate the molecules involved in development of Barrett's esophagus (BE) in human eosinophilic esophagitis (EoE). Histopathological, immunohistochemical, real-time PCR Immuno blot, and ELISA analyses are performed to identify the signature genes and proteins involved in the progression of BE in EoE. We detected characteristic features of BE like intermediate columnar-type epithelial cells, induced BE signature genes like ErbB3, CDX1, ErbB2IP in the esophageal mucosa of patients with EoE. In addition, we had observed several BE-associated proteins such as TFF3, p53 and the progression markers like EGFR, p16, MICA, MICB, and MHC molecules in esophageal biopsies of patients with chronic EoE. Interestingly, we also detected mucin-producing columnar cells and MUC-2, MUC-4, and MUC5AC genes and proteins along with induced IL-9 in patients with chronic EoE. A strong correlation of IL-9 with mucin genes is observed that implicated a possible role for IL-9 in the transformation of esophageal squamous epithelial cells to columnar epithelial cells in patients with EoE. These findings indicate that IL-9 may have an important role in BE development in patients with chronic EoE. We also discovered that IL-9 stimulates mucin-producing and barrier cell transcripts and proteins such CK8/18, GATA4, SOX9, TFF1, MUC5AC, and tight junction proteins in primary esophageal epithelial cells when exposed to IL-9. Taken together, these findings provide evidence that indeed IL-9 has a role in the initiation and progression of BE characteristics like development of mucin-producing columnar epithelial cells in patients with chronic EoE.NEW & NOTEWORTHY Intermediate columnar-type epithelial cells are observed in biopsies of patients with EoE. Induced BE signature genes (CK8/18, CDX1 GATA4, SOX9, and Occludin) were observed in patients with chronic EoE. Induction of IL-9 and its correlation with eosinophils mucin-producing genes and proteins was observed in patients with EoE. Induced IL-9 may be responsible for the development of BE in patients with chronic EoE.

Nontoxic In Vivo Clearable Nanoparticle Clusters for Theranostic Applications.

Disintegrable inorganic nanoclusters (GIONs) with gold seed (GS) coating of an iron oxide core with a primary nanoparticle size less than 6 nm were prepared for theranostic applications. The GIONs possessed a broad near-infrared (NIR) absorbance at ∼750 nm because of plasmon coupling between closely positioned GSs on the iron oxide nanoclusters (ION) surface, in addition to the ∼513 nm peak corresponding to the isolated GS. The NIR laser-triggered photothermal response of GIONs was found to be concentration-dependent with a temperature rise of ∼8.5 and ∼4.5 °C from physiological temperature for 0.5 and 0.25 mg/mL, respectively. The nanoclusters were nonhemolytic and showed compatibility with human umbilical vein endothelial cells up to a concentration of 0.7 mg/mL under physiological conditions. The nanoclusters completely disintegrated at a lysosomal pH of 5.2 within 1 month. With an acute increase of over 400% intracellular reactive oxygen species soon after γ-irradiation and assistance from Fenton reaction-mediated supplemental oxidative stress, GION treatment in conjunction with radiation killed ∼50% of PLC/PRF/5 hepatoma cells. Confocal microscopy images of these cells showed significant cytoskeletal and nuclear damage from radiosensitization with GIONs. The cell viability further decreased to ∼10% when they were sequentially exposed to the NIR laser followed by γ-irradiation. The magnetic and optical properties of the nanoclusters enabled GIONs to possess a T2 relaxivity of ∼223 mM-1 s-1and a concentration-dependent strong photoacoustic signal toward magnetic resonance and optical imaging. GIONs did not incur any organ damage or evoke an acute inflammatory response in healthy C57BL/6 mice. Elemental analysis of various organs indicated differential clearance of gold and iron via both renal and hepatobiliary routes.