Effect of crude polysaccharide from seaweed, Dictyopteris divaricata (CDDP) on gut microbiota restoration and anti-diabetic activity in streptozotocin (STZ)-induced T1DM mice.

Type-1 Diabetes Mellitus (T1DM) is regarded as a multifunctional, immune-related disease which causes massive destruction of islet ß-cells in pancreas resulting in hyperglycemic, hypoinsulinemia and hyperlipidimic conditions. The aim of the present study, was to investigate the hypothesis that streptozotocin (STZ)-induced T1DM in Balb/c mice when treated with crude polysaccharide from seaweed, Dictyopteris divaricata (CDDP) depicts improvement in diabetes-related symptoms. Treatment with CDDP resulted in decreased body weight loss, improved food consumption and water intake disbalances. The CDDP effectively improved fasting blood glucose, oral glucose tolerance (OGTT), serum insulin, insulin secretion, rejuvenation of ß-cells mass, serum lipid profile and pro-inflammatory cytokines levels. Additionally, treatment with CDDP increased the population of beneficial bacteria such as Firmicutes, Bacteroidetes and Lactobacillus at phylum, family and genus levels by 16S rRNA sequencing. Furthermore, immunohistological examination confirmed that CDDP reduces the inflammation and restored the structural morphology of colon and upraised the levels of insulin receptor substrate-1 (IRS-1), Mucin-2 (MUC-2) and tight-junction proteins (TJs) whereby maintaining the gut structures and barrier permeability. Thus, the above presented data, highlights the safe and therapeutic effects of crude polysaccharide (CDDP) from D. divaricata in the treatment and restoration of T1DM disorders and can be used as a food supplement alternative to diabetes medicine.

The Anticancer Potential of Apigenin Via Immunoregulation.

Apigenin is an edible flavonoid widely distributed in natural plants, including most vegetables and fruits. Previous studies have revealed that apigenin possesses multiple biological functions by demonstrating antiinflammatory, anti-oxidative, anti-bacterial, anti-viral, anti-tumor and cardiovascular protective effects. Furthermore, recent progressions have disclosed a novel perspective of the anti-cancer roles of apigenin through its immunoregulatory functions. With the rapid progression of the groundbreaking strategies being developed for cancer immunotherapy, its immunoregulatory roles are being recognized as intriguing features of the multifaceted apigenin. However, the current understanding of this emerging role of apigenin still remains limited. Therefore, in the present review, recent advances on the immunoregulatory properties of apigenin in various diseases with a special focus on neoplasm, are summarized. Clinical strategies of cancer immunotherapy are briefly introduced and findings on apigenin linked to immunoregulatory roles in immunotherapy-associated aspects are brought together. The bioactivity, bioavailability, toxicity and potential of apigenin, to be considered as a therapeutic agent in anti-tumor immunotherapy, is discussed. Disclosed molecular mechanisms underlying the immunoregulatory roles of apigenin in cancer immunotherapy are also summarized. Based on findings from the literature, apigenin has the potential to serve as a prospective adjuvant for anti-cancer immunotherapy and warrants further investigations.

Region-Based Segmentation and Wiener Pilot-Based Novel Amoeba Denoising Scheme for CT Imaging.

Computed tomography (CT) is one of the most common and beneficial medical imaging schemes, but the associated high radiation dose injurious to the patient is always a concern. Therefore, postprocessing-based enhancement of a CT reconstructed image acquired using a reduced dose is an active research area. Amoeba- (or spatially variant kernel-) based filtering is a strong candidate scheme for postprocessing of the CT image, which adapts its shape according to the image contents. In the reported research work, the amoeba filtering is customized for postprocessing of CT images acquired at a reduced X-ray dose. The proposed scheme modifies both the pilot image formation and amoeba shaping mechanism of the conventional amoeba implementation. The proposed scheme uses a Wiener filter-based pilot image, while region-based segmentation is used for amoeba shaping instead of the conventional amoeba distance-based approach. The merits of the proposed scheme include being more suitable for CT images because of the similar region-based and symmetric nature of the human body anatomy, image smoothing without compromising on the edge details, and being adaptive in nature and more robust to noise. The performance of the proposed amoeba scheme is compared to the traditional amoeba kernel in the image denoising application for CT images using filtered back projection (FBP) on sparse-view projections. The scheme is supported by computer simulations using fan-beam projections of clinically reconstructed and simulated head CT phantoms. The scheme is tested using multiple image quality matrices, in the presence of additive projection noise. The scheme implementation significantly improves the image quality visually and statistically, providing better contrast and image smoothing without compromising on edge details. Promising results indicate the efficacy of the proposed scheme.

The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer.

ErbB2 overexpression identifies a subclass of breast cancer as ErbB2-positive that is frequently associated with poor prognosis. Current ErbB2-targeted therapies have profoundly improved patient outcomes, but mutations occurring in ErbB2 have been shown to confer drug resistance. Induction of ErbB2 degradation was proposed as an intriguing strategy to battle with ErbB2-positive breast cancer and reduced mutation-incurred drug resistance. Although multiple HSP90 inhibitors have been demonstrated to effectively trigger ErbB2 degradation, none succeeded in the clinical evaluations. To develop novel ErbB2-targeting strategies, we investigated the endocytic degradation and reversible ubiquitylation of ErbB2 in breast cancer. In this study, we reveal that HSP90 inhibition leads to efficient ubiquitylation and endocytic degradation of ErbB2 through the canonical endo-lysosomal route. USP2 associates with internalized ErbB2 and prevents its lysosomal sorting and degradation via exerting deubiquitylase activity. Accordingly, the USP2 inhibitor ML364 is capable of inducing ErbB2 ubiquitylation and accelerating its turnover. ML364 potentiates the pro-degradation effects of HSP90 inhibitors on ErbB2 and hence sensitizes ErbB2-positive breast cancer cells to HSP90 inhibition. The combination of USP2 and HSP90 inhibitors effectively restrains ErbB2-positive breast cancer xenograft growth in vivo. Based on these observations, we conclude that USP2 safeguards ErbB2 surface levels by antagonizing its ubiquitylation-mediated endocytic degradation, which can be exploited to design novel therapeutic strategies against ErbB2-driven malignancies as combinatorial treatment with HSP90 inhibitors.