Practical Access to Fused Carbazoles via Oxidative Benzannulation and their Photophysical Properties.

An aryne annulation strategy for the synthesis of fused carbazoles is developed using indolyl ß-ketonitrile in a cascade manner. The reaction sequence involves aryne-mediated [2 + 2] cycloaddition cleavage and intramolecular Michael addition, followed by oxidation under transition-metal-free reaction conditions. Subsequently, conversion of benzo[b]carbazole-6-carbonitrile to carbazole quinone is observed upon prolongation of the reaction time. Furthermore, these materials exhibit high quantum efficiency, which promotes the light-emitting diode applications.

Dithiophosphonate-Protected Eight-Electron Superatomic Ag21 Nanocluster: Synthesis, Isomerism, Luminescence, and Catalytic Activity.

The structure-property relationship considering isomerism-tuned photoluminescence and efficient catalytic activity of silver nanoclusters (NCs) is exclusive. Asymmetrical dithiophosphonate NH4[S2P(OR)(p-C6H4OCH3)] ligated first atomically precise silver NCs [Ag21{S2P(OR)(p-C6H4OCH3)}12]PF6 {where, R = nPr (1), Et (2)} were established by single-crystal X-ray diffraction and characterized by electrospray ionization mass spectrometry, NMR (31P, 1H, 2H), X-ray photoelectron spectroscopy, UV-visible, energy-dispersive X-ray spectroscopy, Fourier transforms infrared, thermogravimetric analysis, etc. NCs 1 and 2 consist of eight silver atoms in a cubic framework and enclose an Ag@Ag12-centered icosahedron to constitute an Ag21 core of Th symmetry, which is concentrically inscribed within the S24 snub-cube, P12 cuboctahedron, and the O12 truncated tetrahedron formed by 12 dithiophosphonate ligands. These NCs facilitate to be an eight-electron superatom (1S21P6), in which eight capping Ag atoms exhibit structural isomerism with documented isoelectronic [Ag21{S2P(OiPr)2}12]PF6, 3. In contrast to 3, the stapling of dithiophosphonates in 1 and 2 triggered bluish emission within the 400 to 500 nm region at room temperature. The density functional theory study rationalized isomerization and optical properties of 1, 2, and 3. Both (1, and 2) clusters catalyzed a decarboxylative acylarylation reaction for rapid oxindole synthesis in 99% yield under ambient conditions and proposed a multistep reaction pathway. Ultimately, this study links nanostructures to their physical and catalytic properties.

Role of serum microRNAs as biomarkers for endometriosis, endometrioid carcinoma of ovary & endometrioid endometrial cancer.

Background & objectives: Accurate and early diagnosis is imperial in the management of endometriosis, endometrioid carcinoma of ovary (ECO) and endometrioid endometrial cancer (EC), yet there are no definitive diagnostic methods available for these diseases. Therefore, the present study was aimed to evaluate the diagnostic potential of differentially expressed miRNAs in serum samples of women with endometriosis, ECO and EC to establish them as diagnostic biomarkers. Methods: Blood samples (5 ml) were obtained from 40 patients (n=10/study group) undergoing laparoscopy/laparotomy/hysterectomy. miRNA-rich RNA was extracted from the serum samples, and quantitative real-time (qRT)-PCR was performed to check the expression levels of miR-16, miR-99b, miR-20a, miR-145, miR-143 and miR-125a in all the samples. Receiver operating characteristic (ROC) curve analysis was done to check the diagnostic potential. Results: In endometriosis, miR-16 was downregulated (P<0.05) whereas miR-99b, miR-125a, miR-143 and miR-145 were upregulated (P<0.05). In ECO group, downregulated expression of miR-16 and miR-125a (P<0.05) was observed, whereas miR-99b, miR-143 and miR-145 were upregulated (P<0.05). In endometrioid EC, miR-16, miR-99b, miR-125 and miR-145 were downregulated (P<0.05), whereas miR-143 was upregulated (P<0.05). ROC curve analysis showed that, for endometriosis, miR-99b, miR-125a, miR-143 and miR-145 served as diagnostic markers. miR-145 showed diagnostic power for ECO, and for endometrioid EC, miR-16, miR-99b, miR-125a and miR-145 showed diagnostic potential. Interpretation & conclusions: The present findings suggested that certain circulating miRNAs (miB99b, miR-16, miR-125a, miR-145) might act as indicators and discriminators of endometriosis and endometrioid subtypes of EC and ovarian cancer and might serve as potential biomarkers for early diagnosis and management of these debilitating diseases.

SARS-CoV-2 and the reproductive system: known and the unknown..!!

BACKGROUND: COVID-19 is the most recent zoonotic outbreak of coronaviruses. Mostly, it invades the cells of the respiratory system by binding to the receptor angiotensin-converting enzyme 2 (ACE2) which is also present in other organs like the kidney, testis, ovaries, breast, heart, and intestine, rendering them prone to be infected. The reproductive potential is a must for the sustenance of any species and it is our prime duty to safeguard the reproductive system of the present generation from such a deadly virus. The previously reported coronaviruses like severe acute respiratory syndrome coronavirus (SARS-CoV) had a detrimental impact on reproductive organs. There is a dearth of sufficient research to provide substantial evidence for the harmful effects of this novel virus on the reproductive system. Hence, our review compiles the knowledge available until now to boost research in this regard and to take the necessary steps in time. MAIN BODY OF ABSTRACT: Here we tried to compile all the data available on the effect of SARS-CoV-2 on the reproductive system as well as vertical transmission of the virus. All related articles published from February to August 2020 were reviewed and thoroughly analyzed. SARS-CoV-2 has been found to affect the sperm concentration and motility, thus degrading the fertility of males. In females, it is suspected that this virus affects the oocyte quality and ovarian function, resulting in infertility or miscarriage. Traces of SARS-CoV-2 virus have also been found in the breast milk of the infected mothers and the semen of infected males. Vertical transmission of SARS-CoV-2 has also been reported in some cases. CONCLUSION: Based on the literature review, SARS-CoV-2 seems to have the potential of affecting both male and female reproductive tracts. This review brings together the findings and observations made in the area of reproductive health during the current pandemic. The reproductive system of the young population is preordained for subsequent disorders, infertility, reduced sperm count, and motility. Therefore, the research and medical practices should focus on possible vulnerability being posed by SARS-CoV-2 to the gametes and future generations. We, hereby, recommend close monitoring of young and pregnant COVID-19 patients concerning reproductive health with utmost priority.

Re-annotation of the Theileria parva genome refines 53% of the proteome and uncovers essential components of N-glycosylation, a conserved pathway in many organisms.

BACKGROUND: The apicomplexan parasite Theileria parva causes a livestock disease called East coast fever (ECF), with millions of animals at risk in sub-Saharan East and Southern Africa, the geographic distribution of T. parva. Over a million bovines die each year of ECF, with a tremendous economic burden to pastoralists in endemic countries. Comprehensive, accurate parasite genome annotation can facilitate the discovery of novel chemotherapeutic targets for disease treatment, as well as elucidate the biology of the parasite. However, genome annotation remains a significant challenge because of limitations in the quality and quantity of the data being used to inform the location and function of protein-coding genes and, when RNA data are used, the underlying biological complexity of the processes involved in gene expression. Here, we apply our recently published RNAseq dataset derived from the schizont life-cycle stage of T. parva to update structural and functional gene annotations across the entire nuclear genome. RESULTS: The re-annotation effort lead to evidence-supported updates in over half of all protein-coding sequence (CDS) predictions, including exon changes, gene merges and gene splitting, an increase in average CDS length of approximately 50 base pairs, and the identification of 128 new genes. Among the new genes identified were those involved in N-glycosylation, a process previously thought not to exist in this organism and a potentially new chemotherapeutic target pathway for treating ECF. Alternatively-spliced genes were identified, and antisense and multi-gene family transcription were extensively characterized. CONCLUSIONS: The process of re-annotation led to novel insights into the organization and expression profiles of protein-coding sequences in this parasite, and uncovered a minimal N-glycosylation pathway that changes our current understanding of the evolution of this post-translational modification in apicomplexan parasites.

Correction to: Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential.

Please note, following publication of the original article [1], the authors have advised of two errors that are present in the published article.

Triazole Linked N-Acetylglucosamine Based Gelators for Crude Oil Separation and Dye Removal.

Marine oil-spills have a long-lasting impact on the environment; therefore, it is a major concern in the scientific community to find a solution for remediation. Recently, phase selective organo-gelators emerged as potential materials for removal of oil from water through selective gelation. Herein, we report synthesis of a series of C-6 triazole linked N-acetylglucosamine derivatives, among which three have shown excellent selective gelation of organic solvents, diesel, petrol, and crude oils in water and seawater. We have studied phase selective gelation against different API grade crude oils (from light to heavy), and the gelation was achieved using nontoxic carrier solvent at room temperature in less than 15 min, and gelators were found useful for recovering crude oils. Critical gel concentration (CGC) of crude oil gelators was found to be 2.3-12% (w/v). The variable temperature NMR and FTIR experiments reveal that intermolecular hydrogen bonding was responsible for gel formation. Furthermore, a gelator was utilized for selective dye removal from water.

Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential.

BACKGROUND: Malaria is one of the deadliest infectious diseases caused by protozoan parasite of Plasmodium spp. Increasing resistance to anti-malarials has become global threat in control of the disease and demands for novel anti-malarial interventions. Naturally-occurring coumarins, which belong to a class of benzo-α-pyrones, found in higher plants and some essential oils, exhibit therapeutic potential against various diseases. However, their limited uptake and non-specificity has restricted their wide spread use as potential drug candidates. METHODS: Two series of carbohydrate fused pyrano[3,2-c]pyranone carbohybrids which were synthesized by combination of 2-C-formyl galactal and 2-C-formyl glucal, with various freshly prepared 4-hydroxycoumarins were screened against Plasmodium falciparum. The anti-malarial activity of these carbohybrids was determined by growth inhibition assay on P. falciparum 3D7 strain using SYBR green based fluorescence assay. Haemolytic activity of carbohybrid 12, which showed maximal anti-malarial activity, was determined by haemocompatibility assay. The uptake of the carbohybrid 12 by parasitized erythrocytes was determined using confocal microscopy. Growth progression assays were performed to determine the stage specific effect of carbohybrid 12 treatment on Pf3D7. In silico studies were conducted to explore the mechanism of action of carbohybrid 12 on parasite microtubule dynamics. These findings were further validated by immunofluorescence assay and drug combination assay. RESULTS: 2-C-formyl galactal fused pyrano[3,2-c]pyranone carbohybrid 12 exhibited maximum growth inhibitory potential against Plasmodium with IC50 value of 5.861 µM and no toxicity on HepG2 cells as well as no haemolysis of erythrocytes. An enhanced uptake of this carbohybrid compound was observed by parasitized erythrocytes as compared to uninfected erythrocytes. Further study revealed that carbohybrid 12 arrests the growth of parasite at trophozoite and schizonts stage during course of progression through asexual blood stages. Mechanistically, it was shown that the carbohybrid 12 binds to α,ß-heterodimer of tubulin and affects microtubule dynamics. CONCLUSION: These findings show carbohydrate group fusion to 4-hydroxycoumarin precursor resulted in pyrano-pyranones derivatives with better solubility, enhanced uptake and improved selectivity. This data confirms that, carbohydrate fused pyrano[3,2-c]pyranones carbohybrids are effective candidates for anti-malarial interventions against P. falciparum.

A theoretical study on the dynamics of a compound vesicle in shear flow.

The dynamics of nucleate cells in shear flow is of great relevance in cancer cells and circulatory tumor cells where they determine the flow properties of blood. Buoyed by the success of giant unilamellar vesicles in explaining the dynamics of anucleate cells such as red blood cells, compound vesicles have been suggested as a simple model for nucleate cells. A compound vesicle consists of two concentric unilamellar vesicles with the inner, annular and outer regions filled with aqueous Newtonian solvents. In this work, a theoretical model is presented to study the deformation and dynamics of a compound vesicle in linear shear flow using small deformation theory and spherical harmonics with higher order approximation to the membrane forces. A coupling of viscous and membrane stresses at the membrane interface of the two vesicles results in highly nonlinear shape evolution equations for the inner and the outer vesicles which are solved numerically. The results indicate that the size of the inner vesicle (χ) does not affect the tank-treading dynamics of the outer vesicle. The inner vesicle admits a greater inclination angle than the outer vesicle. However, the transition to trembling/swinging and tumbling is significantly affected. The inner and outer vesicles exhibit identical dynamics in the parameter space defined by the nondimensional rotational (Λan) and extensional (S) strength of the general shear flow. At moderate χ, a swinging mode is observed for the inner vesicle while the outer vesicle exhibits tumbling. The inner vesicle also exhibits modification of the TU mode to IUS (intermediate tumbling swinging) mode. Moreover, synchronization of the two vesicles at higher χ and a Capillary number sensitive motion at lower χ is observed in the tumbling regime. These results are in accordance with the few experimental observations reported by Levant and Steinberg. A reduction in the inclination angle is observed with an increase in χ when the inner vesicle is replaced by a solid inclusion. Additionally, a very elaborate phase diagram is presented in the Λan-S parameter space, which could be tested in future experiments or numerical simulations.

New signaling pathways govern the host response to C. albicans infection in various niches.

Candida albicans, the major invasive fungal pathogen of humans, can cause both debilitating mucosal infections and fatal invasive infections. Understanding the complex nature of the host-pathogen interaction in each of these contexts is essential to developing desperately needed therapies to treat fungal infections. RNA-seq enables a systems-level understanding of infection by facilitating comprehensive analysis of transcriptomes from multiple species (e.g., host and pathogen) simultaneously. We used RNA-seq to characterize the transcriptomes of both C. albicans and human endothelial cells or oral epithelial cells during in vitro infection. Network analysis of the differentially expressed genes identified the activation of several signaling pathways that have not previously been associated with the host response to fungal pathogens. Using an siRNA knockdown approach, we demonstrate that two of these pathways-platelet-derived growth factor BB (PDGF BB) and neural precursor-cell-expressed developmentally down-regulated protein 9 (NEDD9)-govern the host-pathogen interaction by regulating the uptake of C. albicans by host cells. Using RNA-seq analysis of a mouse model of hematogenously disseminated candidiasis (HDC) and episodes of vulvovaginal candidiasis (VVC) in humans, we found evidence that many of the same signaling pathways are activated during mucosal (VVC) and/or disseminated (HDC) infections in vivo. Our analyses have uncovered several signaling pathways at the interface between C. albicans and host cells in various contexts of infection, and suggest that PDGF BB and NEDD9 play important roles in this interaction. In addition, these data provide a valuable community resource for better understanding host-fungal pathogen interactions.

Stereoselective synthesis of natural product inspired carbohydrate fused pyrano[3,2-c]quinolones as antiproliferative agents.

Pyrano[3,2-c]quinolone structural motifs are commonly found in natural products with diverse biological activities. As part of a research programme aimed at developing the efficient synthesis of natural product-like small molecules, we designed and developed the microwave assisted, facile stereoselective synthesis of two series of carbohydrate fused pyrano[3,2-c]quinolone derivatives (n = 23) starting from 2-C-formyl galactal and 2-C-formyl glucal, reacting with various 4-hydroxyquinolones in shorter reaction times (15-20 min). The antiproliferative activity of these synthesized pyrano[3,2-c]quinolones was determined against MCF-7 (breast) and HepG2 (liver) cancer cells. The selected library members displayed low micromolar (3.53-9.68 µM) and selective antiproliferative activity. These findings on carbohydrate fused pyrano[3,2-c]quinolone derivatives are expected to provide new leads for anticancer drug discovery.

Correction: Stereoselective synthesis of natural product inspired carbohydrate fused pyrano[3,2-c]quinolones as antiproliferative agents.

Correction for 'Stereoselective synthesis of natural product inspired carbohydrate fused pyrano[3,2-c]quinolones as antiproliferative agents' by Priti Kumari et al., Org. Biomol. Chem., 2018, DOI: 10.1039/c7ob03186f.

Drosophila anti-nematode and antibacterial immune regulators revealed by RNA-Seq.

BACKGROUND: Drosophila melanogaster activates a variety of immune responses against microbial infections. However, information on the Drosophila immune response to entomopathogenic nematode infections is currently limited. The nematode Heterorhabditis bacteriophora is an insect parasite that forms a mutualistic relationship with the gram-negative bacteria Photorhabdus luminescens. Following infection, the nematodes release the bacteria that quickly multiply within the insect and produce several toxins that eventually kill the host. Although we currently know that the insect immune system interacts with Photorhabdus, information on interaction with the nematode vector is scarce. RESULTS: Here we have used next generation RNA-sequencing to analyze the transcriptional profile of wild-type adult flies infected by axenic Heterorhabditis nematodes (lacking Photorhabdus bacteria), symbiotic Heterorhabditis nematodes (carrying Photorhabdus bacteria), and Photorhabdus bacteria alone. We have obtained approximately 54 million reads from the different infection treatments. Bioinformatic analysis shows that infection with Photorhabdus alters the transcription of a large number of Drosophila genes involved in translational repression as well in response to stress. However, Heterorhabditis infection alters the transcription of several genes that participate in lipidhomeostasis and metabolism, stress responses, DNA/protein synthesis and neuronal functions. We have also identified genes in the fly with potential roles in nematode recognition, anti-nematode activity and nociception. CONCLUSIONS: These findings provide fundamental information on the molecular events that take place in Drosophila upon infection with the two pathogens, either separately or together. Such large-scale transcriptomic analyses set the stage for future functional studies aimed at identifying the exact role of key factors in the Drosophila immune response against nematode-bacteria complexes.

Scale-invariant entropy-based theory for dynamic ordering.

Dynamically Ordered self-organized dissipative structure exists in various forms and at different scales. This investigation first introduces the concept of an isolated embedding system, which embeds an open system, e.g., dissipative structure and its mass and/or energy exchange with its surroundings. Thereafter, scale-invariant theoretical analysis is presented using thermodynamic principles for Order creation, existence, and destruction. The sustainability criterion for Order existence based on its structured mass and/or energy interactions with the surroundings is mathematically defined. This criterion forms the basis for the interrelationship of physical parameters during sustained existence of dynamic Order. It is shown that the sufficient condition for dynamic Order existence is approached if its sustainability criterion is met, i.e., its destruction path is blocked. This scale-invariant approach has the potential to unify the physical understanding of universal dynamic ordering based on entropy considerations.

Synthesis of triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones as anticancer agents and their in silico docking studies.

In the pursuit of novel therapeutic agents, we present a comprehensive study on the design, synthesis, and evaluation of a diverse library of triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones, employing a microwave-assisted synthetic approach via 'click chemistry'. This methodology offers efficient and accelerated access to the glycohybrids, showcasing improved reaction conditions that yield high-quality products. In this research endeavor, we have successfully synthesized a series of twenty-seven triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones. Our investigation extends beyond synthetic endeavors to explore the potential therapeutic relevance of these compounds. We subjected them to rigorous in vitro screening against prominent breast cancer cell lines MCF-7, MDA-MB231, and MDA-MB453. Among the library of compounds synthesized, (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-((5-(4-methoxyphenyl)-7-oxopyrazolo[1,5-a]pyrimidin-1(7H)-yl)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate emerged as a potent compound, exhibiting remarkable anti-cancer activity with an IC50 value of 27.66 µM against the MDA-MB231 cell line. Additionally, (2S,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-((7-oxo-5-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyrimidin-1(7H)-yl)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate displayed notable inhibitory potential against the MCF-7 cell line, with an IC50 value of 4.93 µM. Furthermore, in silico docking analysis was performed to validate our experimental findings. These findings underscore the promise of our triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones as potential anti-cancer agents. This research not only enriches the field of glycohybrid synthesis but also contributes valuable insights into the development of novel anti-cancer therapeutics.

Narcissistic self-sorting in Zn(II) porphyrin derived semiconducting nanostructures.

The narcissistic self-sorted phenomenon is explicitly attributed to the structural similarities in organic molecules. Although such relevant materials are rarely explored, self-sorted structures from macrocyclic π-conjugated-based p- and n-type organic semiconductors facilitate the increase of exciton dissociation and charge separation in bulk heterojunction solar cells. Herein, we report two extended π-conjugated derivatives consisting of zinc-porphyrin-linked benzothiadiazole acting as an acceptor (PB) and anthracene as a donor (PA). Despite having the same porphyrin π-conjugated core in PA and PB, variations in donor and acceptor moieties make the molecular packing form one-dimensional (1D) self-assembled nanofibers via H- and J-type aggregates. Interestingly, a dissimilar aggregate of PA and PB exists as a mixture (PA + PB), promoting narcissistic self-sorted structures. Electrochemical impedance investigation reveals that the electronic characteristics of self-sorting assemblies are influenced by the difference in electrostatic potentials for PA and PB, resulting in a transitional electrical conductivity of 0.14 S cm-1. Therefore, the design of such materials for the fabrication of effective photovoltaics is promoted by these extraordinary self-sorted behaviors in comparable organic π-conjugated molecules.

Efficient and stereoselective synthesis of sugar fused pyrano[3,2-c]pyranones as anticancer agents.

A highly stereoselective, efficient and facile route was achieved for the synthesis of novel and biochemically potent sugar fused pyrano[3,2-c]pyranone derivatives starting from inexpensive, naturally occurring d-galactose and d-glucose. First, ß-C-glycopyranosyl aldehydes were synthesized from these d-hexose sugars in six steps, with overall yields 41-55%. Next, two different 1-C-formyl glycals were synthesized from these ß-C-glycopyranosyl aldehydes by treatment in basic conditions. The optimization of reaction conditions was carried out following reactions between 1-C-formyl galactal and 4-hydroxycoumarin. Next, 1-C-formyl galactal and 1-C-formyl glucal were treated with nine substituted 4-hydroxy coumarins at room temperature (25 °C) in ethyl acetate for ∼1-2 h in the presence of l-proline to obtain exclusively single diastereomers of pyrano[3,2-c]pyranone derivatives in excellent yields. Four compounds were found to be active for the MCF-7 cancer cell line. The MTT assay, apoptosis assay and migration analysis showed significant death of the cancer cells induced by the synthesized compounds.

Analysis and Visualization of Longitudinal Genomic and Clinical Data from the AACR Project GENIE Biopharma Collaborative in cBioPortal.

International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data from 19 cancer centers, makes data from >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model. Several thousand of these cases are now also available in cBioPortal. We have significantly enhanced the functionalities of cBioPortal to support the visualization and analysis of this rich clinico-genomic linked dataset, as well as datasets generated by other centers and consortia. Examples of these enhancements include (i) visualization of the longitudinal clinical and genomic data at the patient level, including timelines for diagnoses, treatments, and outcomes; (ii) the ability to select samples based on treatment status, facilitating a comparison of molecular and clinical attributes between samples before and after a specific treatment; and (iii) survival analysis estimates based on individual treatment regimens received. Together, these features provide cBioPortal users with a toolkit to interactively investigate complex clinico-genomic data to generate hypotheses and make discoveries about the impact of specific genomic variants on prognosis and therapeutic sensitivities in cancer. SIGNIFICANCE: Enhanced cBioPortal features allow clinicians and researchers to effectively investigate longitudinal clinico-genomic data from patients with cancer, which will improve exploration of data from the AACR Project GENIE Biopharma Collaborative and similar datasets.

Revisiting the forgotten remnant: Imaging spectrum of Meckel's diverticulum.

Meckel's diverticulum is a true diverticulum of the alimentary tract occurring resulting from the persistence of remnants of the vitello-intestinal duct. They are often asymptomatic and incidentally diagnosed during surgery. Complications such as intestinal obstruction, diverticulitis, intestinal haemorrhage and perforation may occur with Meckel's diverticulum, which renders them symptomatic. The clinical and imaging diagnosis of Meckel's diverticulum is very challenging. As a result of the rare occurrence of complicated Meckel's diverticulum and the difficult preoperative diagnosis, knowledge of its imaging features is limited. The presented case series describes a spectrum of complications caused by Meckel's diverticulum and its CT imaging features. It highlights the importance of a high clinical suspicion by carefully searching for a Meckel's diverticulum on CT in its characteristic location to avoid missing it preoperatively.

Promoter methylation status of key genes and its implications in the pathogenesis of endometriosis, endometrioid carcinoma of ovary and endometrioid endometrial cancer.

Background: Epigenetic processes play an important role in various physiological processes as well as in the pathogenesis of many diseases. The role of altered DNA methylation in the pathogenesis of endometriosis and associated ovarian and endometrial cancers has not been explored in detail. Therefore, this study aimed to determine the promoter methylation status of genes involved in key biological processes in the pathogenesis of these three gynecological diseases. Methods: Tissue samples of endometriosis, endometrioid carcinoma of the ovary, endometrioid endometrial cancer, and control endometrium (n = 10 each) were obtained. DNA was extracted and subjected to bisulfite conversion using commercially available kits. The methylation status of COX2, VEGF, HIF1A, TNF, MYC, and TP53 genes was checked by methylation-specific PCR. The mRNA levels of MYC and TP53 were determined using qRT-PCR in all tissue samples. Results: The promoter methylation status of COX2, VEGF, HIF1A, and TNF genes was significantly reduced in all three diseased study subjects (P < 0.05), whereas no significant difference was observed in the promoter methylation frequency of MYC and TP53 genes. Transcriptional expression of the MYC gene was significantly increased in all diseased groups (P < 0.001) whereas, transcriptional expression of the TP53 gene was significantly reduced in endometriosis and endometrioid carcinoma of the ovary and significantly increased in endometrioid endometrial cancer subjects compared to control subjects (P < 0.001). Conclusion: The findings suggest that the promoter regions of pro-inflammatory and pro-angiogenic genes involved in the common molecular pathophysiology of these three disorders were significantly hypomethylated and could be the reason for their over-expression associated with them. This indicates the role of epigenetics in the pathogenesis of these three diseases.