Reactive oxidative species (ROS) toxicity remains an undisputed cause and link between Alzheimer’s disease (AD) and Type-2 Diabetes Mellitus (T2DM). Patients with both AD and T2DM have damaged, oxidized DNA, RNA, protein and lipid products that can be used as possible disease progression markers. Although the oxidative stress has been anticipated as a main cause in promoting both AD and T2DM, multiple pathways could be involved in ROS production. The focus of this review is to summarize the mechanisms involved in ROS production and their possible association with AD and T2DM pathogenesis and progression. We have also highlighted the role of current treatments that can be linked with reduced oxidative stress and damage in AD and T2DM.

Background: Relatively few genes have been shown to directly affect the metastatic phenotype of breast cancer epithelial cells in vivo. The Rho family of proteins, including the Rho, Rac and Cdc42 subfamilies, are related to the small GTP binding protein Ras and regulate diverse biological processes including gene transcription, cytoskeletal organization, cell proliferation and transformation. The effects of Cdc42, Rac and Rho on the actin cytoskeleton suggested a possible role for Rho proteins in cellular motility and metastasis, however a formal analysis of the role of Rho proteins in breast cancer cellular growth and metastasis in vivo had not previously been performed. Materials and Methods:We generated a panel of MTLn3 rat mammary adenocarcinoma cells that expressed similar levels of dominant inhibitory mutants of Cdc42-, Rac-and Rho-dependent signaling, to examine the contribution of these GTPases to cell spreading, guided chemotaxis, and metastasis in vivo. The ability of Rho proteins to regulate intravasation into the peripheral blood was determined by implanting MTLn3 cell stable dominant negative lines in nude mice and measuring the formation of breast cancer cell colonies grown from the peripheral blood. Serial sectioning of the lungs was performed to determine the presence of metastasis in mice in which mammary tumors expressing the dominant negative Rho family proteins had grown to a similar size. Results: Cell spreading of MTLn3 cells was selectively abrogated by N17Rac1. N19RhoA and N17Cdc42 reduced the number of focal contacts (FCs) and disrupted the colocalization of vinculin with phosphotyrosine at FCs. While N17Rac1 and N17Cdc42 preferentially inhibited colony formation in soft agar, all three GTPases affected cell growth in vivo. To distinguish effects on tumorigenicity from intravasation into the bloodstream, implanted tumors were grown to the same size in nude mice. Each dominant inhibitory Rho protein reduced intravasation into the peripheral blood. Lung metastasis of MTLn3 cells was also abrogated by the dominant inhibitory Rho proteins, despite the presence of residual CFU. Conclusions: These studies demonstrate for the first time a critical role for the Rho GTPases involving independent signaling pathways to limit mammary tumor cellular growth and metastasis in vivo.

The observations suggest that ONOO- and perhaps other reactive oxygen species are being produced in the sickle cell kidney. The mechanism may be ischemia/reperfusion due to intermittent vascular occlusion by sickle cells. The resulting hypoxia could result in iNOS activation, superoxide radical and peroxynitrite formation. Two consequences of these reactions appear to be nitration of tyrosine residues of some renal proteins and enhanced apoptosis.

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Multi-scale models integrating biomolecular data from genetic, transcriptional, and translational levels, coupled with extracellular microenvironments can assist in decoding the complex mechanisms underlying system-level diseases such as cancer. To investigate the emergent properties and clinical translation of such cancer models, we present Theatre for in silico Systems Oncology (TISON, https://tison.lums.edu.pk), a next-generation web-based multi-scale modeling and simulation platform for in silico systems oncology. TISON provides a “zero-code” environment for multi-scale model development by seamlessly coupling scale-specific information from biomolecular networks, microenvironments, cell decision circuits, in silico cell lines, and organoid geometries. To compute the temporal evolution of multi-scale models, a simulation engine and data analysis features are also provided. Furthermore, TISON integrates patient-specific gene expression data to evaluate patient-centric models towards personalized therapeutics. Several literature-based case studies have been developed to exemplify and validate TISON’s modeling and analysis capabilities. TISON provides a cutting-edge multi-scale modeling pipeline for scale-specific as well as integrative systems oncology that can assist in drug target discovery, repositioning, and development of personalized therapeutics.

The study was carried out to explore the effects of replacing wheat straw with fungal treated wheat straw as an ingredient of total mixed ration (TMR) on the growth performance and nutrient digestibility in Nili Ravi buffalo male calves. Fungal treated wheat straw was prepared using Arachniotus sp. Four TMRs were formulated where wheat straw was replaced with 0 (TMR1), 33 (TMR2), 67 (TMR3), and 100% (TMR4) fungal treated wheat straw in TMR. All TMRs were iso-caloric and iso-nitrogenous. The experimental TMRs were randomly assigned to four groups of male calves (n = 6) according to completely randomized design and the experiment continued for four months. The calves fed TMR2 exhibited a significant improve in dry matter intake, average daily weight gain, feed conversion ratio and feed economics compared to other groups. The same group also showed higher digestibility of dry matter, crude protein, neutral-, and acid detergent fibers than those fed on other TMRs. It is concluded that TMR with 33% fungal-treated wheat straw replacement has a potential to give an enhanced growth performance and nutrient digestibility in male Nili Ravi buffalo calves.

The study was planned to investigate the effects of dried citrus pulp on nutrient intake, digestibility, nitrogen balance, blood metabolites, growth performance and economics in Nilli Ravi buffalo calves. Twenty buffalo male calves of 18 to 24 months of age having 200 to 250 kg body weight were used in a randomized complete block design. Four iso-caloric and iso-nitrogenous diets containing 5, 10, 15 and 20% dried citrus pulp were formulated. The experiment lasted for adaptation period while last five days of each month served as collection period. Feed was offered ad libitum twice a day. Animals were weighed fortnightly before morning feeding to assess their growth performance. The results showed non-significant effects of various levels of dried citrus pulp on nutrient intake and digestibility. Nitrogen metabolism was also remained unaltered among the treatments. There were non-significant differences in weight gain and blood metabolites in calves fed various levels of dried citrus pulp. However, a linear reduction in price per kg diet was observed as the level of dried citrus pulp was increased from 5 to 20% in the diet. The study showed that dried citrus pulp can be used successfully up to 20% in the diet of calves without any ill effect on feed intake, digestibility and growth performance.

Breast cancer poses a serious health risk for women throughout the world. Among the Asian population, Pakistani women have the highest risk of developing breast cancer. One out of nine women is diagnosed with breast cancer in Pakistan. The etiology and the risk factor leading to breast cancer are largely unknown. In the current study the risk factors that are most pertinent to the Pakistani population, the etiology, molecular mechanisms of tumor progression, and therapeutic targets of breast cancer are studied. A correlative, cross-sectional, descriptive, and questionnaire-based study was designed to predict the risk factors in breast cancer patients. Invasive Ductal Carcinoma (90%) and grade-II tumor (73.2%) formation are more common in our patient’s data set. Clinical parameters such as mean age of 47.5 years (SD ± 11.17), disturbed menstrual cycle (> 2), cousin marriages (repeated), and lactation period (< 0.5 Y) along with stress, dietary and environmental factors have an essential role in the development of breast cancer. In addition to this in silico analysis was performed to screen the miRNA regulating the TGF-beta pathway using TargetScanHuman, and correlation was depicted through Mindjet Manager. The information thus obtained was observed in breast cancer clinical samples both in peripheral blood mononuclear cells, and biopsy through quantitative real-time PCR. There was a significant dysregulation (**P>0.001) of the TGF-β1 signaling pathway and the miRNAs (miR-29a, miR-140, and miR-148a) in patients’ biopsy in grade and stage specifically, correlated with expression in blood samples. miRNAs (miR-29a and miR-140, miR-148a) can be an effective diagnostic and prognostic marker as they regulate SMAD4 and SMAD2 expression respectively in breast cancer blood and biopsy samples. Therefore, proactive therapeutic strategies can be devised considering negatively regulated cascade genes and amalgamated miRNAs to control breast cancer better.