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Artocarpus heterophyllus Lam., which is commonly known as jackfruit is a tropical fruit, belonging to Moraceae family, native to Western Ghats of India and common in Asia, Africa, and some regions in South America. It is known to be the largest edible fruit in the world. The Jackfruit is an extremely versatile and sweet tasting fruit that possess high nutritional value. Jackfruit is rich in nutrients including carbohydrates, proteins, vitamins, minerals, and phytochemicals. The jackfruit has diverse medicinal uses especially antioxidant, anti-inflammatory, antimicrobial and antiviral properties, anticancer and antifungal activity, anthelminthic activity. Traditionally, this plant is used in the treatment of various diseases especially for treatment against inflammation, malarial fever, diarrhoea, diabetes and tapeworm infection. Jackfruit is a good natural source of phytochemicals such as phenolics, flavonoids and tannins, saponins. The health benefits of jackfruit have been attributed to its wide range of physicochemical applications. The use of jackfruit bulbs and its parts has also been reported since ancient times for their therapeutic qualities. The beneficial physiological effects may also have preventive application in a variety of pathologies.

Background Increased risk of a second primary malignancy (SPM) before or after diagnosis of anal squamous cell carcinoma (ASCC) has been reported in a previous single‐institution study. We hypothesize that patients diagnosed with ASCC are at increased risk for developing SPMs before or after the diagnosis of ASCC. The primary objective of this study was to identify the diagnoses of cancer most likely to occur as SPMs before or after ASCC. Methods This work employs the Surveillance, Epidemiology, and End Results (SEER) Program registry data to conduct a US‐population‐based study of patients diagnosed with ASCC between 1975 and 2016. In patients diagnosed with ASCC, we evaluated the risk of SPMs and the risk of developing ASCC as an SPM after another cancer using standardized incidence ratios (SIR) for all SPMs by calculating the ratio of observed events in the ASCC cohort compared to expected (O/E) events in a matched reference cohort of the general population. Results A total of 7,594 patients with primary ASCC were included. Patients with ASCC were at increased risk of the diagnosis of an SPM (SIR = 1.45), particularly cancers of the lung, vulva, oropharynx, or colon. Patients with ASCC had an increased rate of previous malignancy (SIR = 1.23), especially Kaposi sarcoma or vulvar cancer. Overall elevated incidence of SPMs was unrelated to prior radiation treatment. Radiation treatment was associated with increased risk for SPMs in the female genital system but appeared protective against prostate cancer as SPMs. Conclusions Our findings support increased surveillance and screening for second malignancies in patients with these diagnoses, as patients with ASCC are often either survivors of a prior cancer diagnosis or are at increased risk of developing later malignancies., Survivors of anal squamous cell carcinoma are at increased risk for particular second malignancies and should be screened for these. Risk of second malignancies is sometimes related to radiation therapy, but radiation can also be protective against second cancers in some cases.

A lysine-to-methionine mutation at lysine 27 of histone 3 (H3K27M) has been shown to promote oncogenesis in a subset of pediatric gliomas. While there is evidence that this "oncohistone" mutation acts by inhibiting the histone methyltransferase PRC2, the details of this proposed mechanism nevertheless continue to be debated. Recent evidence suggests that PRC2 must simultaneously bind both H3K27M and H3K27me3 to experience competitive inhibition of its methyltransferase activity. In this work, we used PRC2 inhibitor treatments in a transgenic H3K27M cell line to validate this dependence in a cellular context. We further used designer chromatin inhibitors to probe the geometric constraints of PRC2 engagement of H3K27M and H3K27me3 in a biochemical setting. We found that PRC2 binds to a bivalent inhibitor unit consisting of an H3K27M and an H3K27me3 nucleosome and exhibits a distance dependence in its affinity for such an inhibitor, which favors closer proximity of the 2 nucleosomes within a chromatin array. Together, our data precisely delineate fundamental aspects of the H3K27M inhibitor and support a model wherein PRC2 becomes trapped at H3K27M-H3K27me3 boundaries.

Polycomb Repressive Complex 2 (PRC2) catalyzes mono-, di-, and trimethylation of lysine 27 on histone H3 (H3K27me1-3) to control expression of genes important for differentiation and maintenance of cell identity. PRC2 activity is regulated by a number of different inputs, including allosteric activation by its product, H3K27me3. This positive feedback loop is thought to be important for the establishment of large domains of condensed heterochromatin. In addition to other chromatin modifications, ancillary subunits of PRC2, foremost JARID2, affect the rate of H3K27 methylation. Many gaps remain in our understanding of how PRC2 integrates these various signals to determine where and when to deposit H3K27 methyl marks. In this study, we utilize designer chromatin substrates to demonstrate that propagation of H3K27 methylation by the PRC2 core complex has geometrically defined preferences that are overridden by the presence of JARID2. Our studies also show that phosphorylation of JARID2 can partially regulate its ability to stimulate PRC2 activity. Collectively, these biochemical insights further our understanding of the mechanisms that govern PRC2 activity, and highlight a role for JARID2 in de novo deposition of H3K27me3-containing repressive domains.

Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2), the enzyme that catalyzes monomethylation, dimethylation, and trimethylation of lysine 27 on histone H3 (H3K27). Trimethylation at H3K27 (H3K27me3) is associated with transcriptional silencing of developmentally important genes. Intriguingly, H3K27me3 is mutually exclusive with H3K36 trimethylation on the same histone tail. Disruptions in this cross-talk result in aberrant H3K27/H3K36 methylation patterns and altered transcriptional profiles that have been implicated in tumorigenesis and other disease states. Despite their importance, the molecular details of how PRC2 “senses” H3K36 methylation are unclear. We demonstrate that PRC2 is activated in cis by the unmodified side chain of H3K36, and that this activation results in a fivefold increase in the k(cat) of its enzymatic activity catalyzing H3K27 methylation compared with activity on a substrate methylated at H3K36. Using a photo-cross-linking MS strategy and histone methyltransferase activity assays on PRC2 mutants, we find that EZH2 contains a specific sensing pocket for the H3K36 methylation state that allows the complex to distinguish between modified and unmodified H3K36 residues, altering enzymatic activity accordingly to preferentially methylate the unmodified nucleosome substrate. We also present evidence that this process may be disrupted in some cases of Weaver syndrome.

Locally advanced rectal cancer has broadly been defined as T3, T4, or lymph node-positive disease. In the 1990s, adjuvant chemoradiation was considered the optimal management for locally advanced rectal cancer. However, the paradigm shifted when the German CAO/ARO/AIO-94 Rectal Cancer trial established neoadjuvant chemoradiation as the standard of care, based on reduced rates of toxicity and local recurrence, as well as higher rates of sphincter preservation compared with postoperative chemoradiation. Both short-course radiation and long-course chemoradiation are currently accepted methods for neoadjuvant treatment, with recent trials showing equivalence in outcomes. While surgery remains the cornerstone of treatment, there are data supporting the use of magnetic resonance imaging for risk stratification in rectal cancer and encouraging prospective data regarding nonoperative management. This review summarizes data on the evolution of treatment for locally advanced rectal cancer and discusses emerging evidence for nonoperative management.

This article uses daily market value data on credit default swap spreads and intraday stock prices to measure systemic risk in the insurance sector. Using the systemic risk measure, we examine the interconnectedness between banks and insurers with Granger causality tests. Based on linear and nonlinear causality tests, we find evidence of significant bidirectional causality between insurers and banks. However, after correcting for conditional heteroskedasticity, the impact of banks on insurers is stronger and of longer duration than the impact of insurers on banks. Stress tests confirm that banks create significant systemic risk for insurers but not vice versa. INTRODUCTION Systemic risk is often triggered by financial institutions that are too big to fail or too interconnected to fail. From a statistical perspective, systemic risk involves the comovement of key financial variables measuring the health or stability of financial institutions; it has also been described as the potential for multiple simultaneous defaults of major financial institutions. Traditional measures such as correlation coefficients generally are not adequate to measure systemic risk because systemic risk tends to involve tail behavior, which is not captured by conventional measures. Conventional measures also rely on balance sheet or accounting information that is only available on a relatively low-frequency basis and often with a lag. There is a growing literature on systemic risk in banking, as banks have long been known to be a source of systemic risk. However, little research has been conducted on measuring systemic risk in the insurance industry. (1) In the past, researchers argued that insurers were not systemically risky because they lacked the "special character" of banks, primarily the susceptibility to bank runs due to the liquidity of bank deposits (Swiss Re, 2003). However the near collapse and government bailout of American International Group (AIG) has challenged this traditional view of insurance. Two prior papers measure systemic risk in banking and insurance using market data. Billio et al. (2011) propose several econometric measures of systemic risk to capture the interconnectedness among the monthly stock returns of hedge funds, banks, brokers, and insurance companies based on principal components analysis and linear Granger causality tests. They find that all four sectors have become highly interrelated over the past decade, increasing the level of systemic risk in the finance and insurance industries. Acharya et al. (2010) model systemic risk using daily stock price data. An institution's contribution to systemic risk, denoted systemic expected shortfall (SES), is its propensity to be undercapitalized when the system as a whole is undercapitalized. They provide empirical evidence of the ability of SES to predict emerging systemic risk during the financial crisis of 2007-2009. This article adds to the sparse information on the interconnectedness of the banking and insurance industries. The purpose of the article is to create and implement a robust systemic risk measure for the insurance sector and investigate the interconnectedness between the banking and insurance industries during the financial crisis using this measure. The systemic risk measure is based on Huang et al. (2009) and relies on daily-frequency market data on credit default swap (CDS) spreads as well as intraday trading data on stock prices. (2) This measure is risk neutral, forward looking, and economically intuitive. Also, the direction of any interconnectedness found between banking and insurance is investigated using linear and nonlinear Granger causality tests, providing information on whether the insurance industry is the source or victim of systemic risk. By way of preview, we find linear and nonlinear causal effects between systemic risk measures of banks and insurers in both directions. …