Cancer Vaccines in the Immunotherapy Era: Promise and Potential.

Therapeutic vaccines are a promising alternative for active immunotherapy for different types of cancers. Therapeutic cancer vaccines aim to prevent immune system responses that are not targeted at the tumors only, but also boost the anti-tumor immunity and promote regression or eradication of the malignancy without, or with minimal, adverse events. Clinical trial data have pushed the development of cancer vaccines forward, and the US Food and Drug Administration authorized the first therapeutic cancer vaccine. In the present review, we discuss the various types of cancer vaccines and different approaches for the development of therapeutic cancer vaccines, along with the current state of knowledge and future prospects. We also discuss how tumor-induced immune suppression limits the effectiveness of therapeutic vaccinations, and strategies to overcome this barrier to design efficacious, long-lasting anti-tumor immune responses in the generation of vaccines.

Chemotherapy-Mediated Neuronal Aberration.

Chemotherapy is a life-sustaining therapeutic option for cancer patients. Despite the advancement of several modern therapies, such as immunotherapy, gene therapy, etc., chemotherapy remains the first-line therapy for most cancer patients. Along with its anti-cancerous effect, chemotherapy exhibits several detrimental consequences that restrict its efficacy and long-term utilization. Moreover, it effectively hampers the quality of life of cancer patients. Cancer patients receiving chemotherapeutic drugs suffer from neurological dysfunction, referred to as chemobrain, that includes cognitive and memory dysfunction and deficits in learning, reasoning, and concentration ability. Chemotherapy exhibits neurotoxicity by damaging the DNA in neurons by interfering with the DNA repair system and antioxidant machinery. In addition, chemotherapy also provokes inflammation by inducing the release of various pro-inflammatory cytokines, including NF-kB, IL-1ß, IL-6, and TNF-α. The chemotherapy-mediated inflammation contributes to chemobrain in cancer patients. These inflammatory cytokines modulate several growth signaling pathways and reactive oxygen species homeostasis leading to systemic inflammation in the body. This review is an effort to summarize the available information which discusses the role of chemotherapy-induced inflammation in chemobrain and how it impacts different aspects of therapeutic outcome and the overall quality of life of the patient. Further, this article also discusses the potential of herbal-based remedies to overcome chemotherapy-mediated neuronal toxicity as well as to improve the quality of life of cancer patients.

Efficacy of Bioactive Compounds in the Regulation of Metabolism and Pathophysiology in Cardiovascular Diseases.

PURPOSE OF REVIEW: An imbalance in reactive oxygen species (ROS) homeostasis can wreak damage to metabolic and physiological processes which can eventually lead to an advancement in cardiovascular diseases (CVD). Mitochondrial dysfunction is considered as a key source of ROS. The purpose of the current review is to concisely discuss the role of bioactive compounds in the modulation of cardiovascular metabolism and their potential application in the management of cardiovascular diseases. RECENT FINDINGS: Recently, it has been shown that bioactive compounds exhibit immunomodulatory function by regulating inflammatory pathways and ROS homeostasis. It has also been reported that bioactive compounds regulate mitochondria dynamics, thus modulating the autophagy and energy metabolism in the cells. In the present article, we have discussed the roles of different bioactive compounds in the modulation of different inflammatory drivers. The functional properties of bioactive compounds in mitochondrial dynamics and its impact on cardiac disease protection have been briefly summarized. Furthermore, we have also discussed various aspects of bioactive compounds with respect to metabolism, immune modulation, circadian rhythm, and its impact on CVD's pathophysiology.

Machine Learning and Image Processing Enabled Evolutionary Framework for Brain MRI Analysis for Alzheimer's Disease Detection.

Alzheimer's disease is characterized by the presence of abnormal protein bundles in the brain tissue, but experts are not yet sure what is causing the condition. To find a cure or aversion, researchers need to know more than just that there are protein differences from the usual; they also need to know how these brain nerves form so that a remedy may be discovered. Machine learning is the study of computational approaches for enhancing performance on a specific task through the process of learning. This article presents an Alzheimer's disease detection framework consisting of image denoising of an MRI input data set using an adaptive mean filter, preprocessing using histogram equalization, and feature extraction by Haar wavelet transform. Classification is performed using LS-SVM-RBF, SVM, KNN, and random forest classifier. An adaptive mean filter removes noise from the existing MRI images. Image quality is enhanced by histogram equalization. Experimental results are compared using parameters such as accuracy, sensitivity, specificity, precision, and recall.

The HBx oncoprotein of hepatitis B virus potentiates cell transformation by inducing c-Myc-dependent expression of the RNA polymerase I transcription factor UBF.

BACKGROUND: The HBx oncoprotein of hepatitis B virus has been implicated in the development and progression of hepatocellular carcinoma (HCC). HBx engages multiple signalling and growth-promoting pathways to induce cell proliferation and enhance ribosome biogenesis. Interestingly, the levels of Upstream Binding Factor (UBF) required for rDNA transcription and ribosome biogenesis are found elevated in the HCC patients. However, the molecular mechanism of UBF overexpression under the HBx microenvironment and consequent cell transformation remains elusive. METHODS: The UBF gene expression was investigated after co-expressing HBx in immortalized human hepatocytes (IHH) and human hepatoma Huh7 cells. Gene expression analysis involved estimation of mRNA level by real-time PCR, western blotting of protein, chromatin immune-precipitation assay, BrdU incorporation assay and soft agar colony formation assay. UBF expression was also investigated in an HBx transgenic mouse model of HCC to get a better mechanistic insight under more physiological conditions. RESULTS: Ectopic expression of HBx in IHH as well as Huh7 cells led to a marked increase in UBF expression both at mRNA and protein levels. Elevated levels of UBF were also observed in the hepatic tumors of HBx transgenic mice. Our ChIP studies revealed a marked increase in the occupancy of c-Myc on the UBF gene promoter in the presence of HBx and increase in its transcription. Enhanced UBF expression under the HBx microenvironment led to a marked increase in cell proliferation and transformation of IHH cells. CONCLUSIONS: Our study provides some compelling evidences in support of HBx-mediated increase in UBF levels that abets oncogenic onslaught in hepatic cells by increasing rDNA transcription and ribosome biogenesis.

Hepatitis B virus X protein and c-Myc cooperate in the upregulation of ribosome biogenesis and in cellular transformation.

Viral and cellular oncogenes are well known to enhance rRNA synthesis, leading to increased ribosome biogenesis and cell proliferation. Our study on the molecular underpinnings of the interaction between viral HBx and c-Myc, which is implicated in the development of hepatocellular carcinoma, showed a marked increase in the biosynthesis of rRNA, ribosomes and protein in hepatoma cells. A profound alteration in the nucleolar morphology and biochemical content of these cells was also observed. Increased biosynthetic activity was associated with increased cell proliferation and transformation of immortalized human hepatocytes. Furthermore, inhibition of RNA polymerase III activity impaired the proliferative advantage of hepatoma cells and transformation of immortalized hepatocytes as effectively as cisplatin treatment. These findings were corroborated in a transgenic HBx-myc microenvironment, in which an elevated hepatic level of rRNA was associated with conspicuous morphological and biochemical changes in the hepatocytic nucleoli. Thus, HBx and c-Myc seem to work cooperatively to support ribosome biogenesis and cellular transformation.

Screening of Bacterial Strains for Polygalacturonase Activity: Its Production by Bacillus sphaericus (MTCC 7542).

At present almost all the pectinolytic enzymes used for industrial applications are produced by fungi. There are a few reports of pectinase production by bacterial strains. Therefore, in the present study, seventy-four bacterial strains, isolated from soil and rotten vegetable samples, were screened for polygalacturonase production. The strain PG-31, which gave maximum activity, was identified as Bacillus sphaericus (MTCC 7542). Maximal quantities of polygalacturonase were produced when a 16-hours-old inoculum was used at 7.5% (v/v) in production medium and incubated in shaking conditions (160 rpm) for 72 hours. The optimal temperature and pH for bacterial growth and polygalacturonase production were found to be 30°C and 6.8, respectively. Maximum enzyme production resulted when citrus pectin was used as the carbon source at a concentration of 1.25% (w/v), whereas other carbon sources led to a decrease (30%-70%) in enzyme production. Casein hydrolysate and yeast extract used together as organic nitrogen source gave best results, and ammonium chloride was found to be the most suitable inorganic nitrogen source. The supplementation of media with 0.9% (w/v) D-galacturonic acid led to a 23% increase in activity. Bacillus sphaericus, a bacterium isolated from soil, produced good amount of polygalacturonase activity at neutral pH; hence, it would be potentially useful to increase the yield of banana, grape, or apple juice.

Chemopreventive and anti-cancer properties of the aqueous extract of flowers of Butea monosperma.

ETHNOPHARMACOLOGICAL RELEVANCE: Butea monosperma (Lam.) (Fabaceae) popularly known as 'flame of the forest' has been widely used in the traditional Indian medical system of 'Ayurveda' for the treatment of a variety of ailments including liver disorders. AIM OF THE STUDY: To evaluate the antioxidative, anti-inflammatory, hepatoprotective and anti-cancer activities of the aqueous extract of Butea monosperma flowers. MATERIALS AND METHODS: Dried flowers of Butea monosperma were extracted with water. The extract was tested for its anti-proliferative, pro-apoptotic and anti-carcinogenic effects in hepatoma cell lines. The chemopreventive and anti-angiogenic effects of the extract were evaluated by its daily oral administration in a HBV-related X15-myc mouse model of hepatocellular carcinoma (HCC). RESULTS: Treatment with the aqueous extract inhibited cell proliferation and accumulation of cells in G1 phase. This was accompanied by a marked reduction in the levels of activated Erk1/2 and SAPK/JNK and induction of apoptotic cell death. Oral administration of the extract in transgenic mice conferred hepatoprotection as is evident from normal serum ALT levels and improved liver histopathology and lowered serum VEGF level. CONCLUSIONS: The ability of aqueous extract of Butea monosperma flowers to impose growth arrest and trigger pro-apoptotic death in cell culture strongly correlated with its strong chemopreventive effect in vivo when given orally.