Nanotechnology-based cancer chemoprevention in glioblastoma.

Brain tumours are heterogeneous and are classified comprehensively into molecular subtypes based on genetic alterations. Glioblastoma rapid progression, drug resistance, and recurrence have been scientifically linked to several factors, including its rapid growth rate, loss of apoptosis, pro-survival signalling, molecular heterogeneities and hallmark features to infiltrate vital brain structures. Because of the growing demand for design and development of delivery systems to overcome the existing limitations with the current therapeutic strategies, researchers are exploiting multifaceted aspects of nanotechnology to improve delivery of the drug payload. Firstly, nanotechnology procedures can improve the drug delivery methods with the help of nanoparticles (NPs) based nanovectors that can efficiently cross blood-brain barrier. Secondly, NPs also improve the cellular uptake of the drug as they can efficiently bind with the cell surface. Thirdly, NPs make the delivery of siRNAs and peptides possible, which can suppress the resistance of glioblastoma against TMZ or other chemo-preventive drugs. Fourthly, the use of metal NPs increases the efficiency of scanning or magnetic resonance imaging (MRI) procedures as they can produce contrasts in it. Lastly, NPs make it possible to use highly targeted co-administered strategies like chemoprevention and near infrared (NIR) or radiotherapy (RT). Hence, nanotechnology offers several promising solutions against glioblastoma by countering it on many fronts.

Molecular basis of acute coronary syndrome.

Cardiovascular diseases (CVD) comprise of various heart and blood vessels-related diseases. Acute coronary syndrome (ACS) is one of them. Basic researchers and cardiologists have witnessed landmark developments related to ACS and despite rapid refinement in our understanding; scientists are seeking answers for more questions. Scientists have mapped wide ranging proteins and intricate protein networks which play central role in the pathogenesis in ACS. In this review, we have attempted to summarize underlying causes of ACS. Better understanding of the disease pathology will enable us to get a step closer to an effective clinical management.

Regulation of RUNX proteins by long non-coding RNAs and circular RNAs in different cancers.

RUNX proteins have been shown to behave as "double-edge sword" in wide variety of cancers. Discovery of non-coding RNAs has played linchpin role in improving our understanding about the post-transcriptional regulation of different cell signaling pathways. Several new mechanistic insights and distinct modes of cross-regulation of RUNX proteins and non-coding RNAs have been highlighted by recent research. In this review we have attempted to provide an intricate interplay between non-coding RNAs and RUNX proteins in different cancers. Better conceptual and mechanistic understanding of layered regulation of RUNX proteins by non-coding RNAs will be helpful in effective translation of the laboratory findings to clinically effective therapeutics.

Regulation of TGFß/SMAD signaling by long non-coding RNAs in different cancers: Dark Knight in the Castle of molecular oncology.

One of the complex themes in recent years has been the multi-layered regulation of TGFß signaling in cancer cells. TGFß/SMAD signaling pathway is a highly complicated web of proteins which work spatio-temporally to regulate multiple steps of carcinogenesis. TGFß/SMAD has been shown to dualistically regulate cancer progression. Therefore, TGFß/SMAD signaling behaves as a "double-edged sword" in molecular oncology. Accordingly, regulation of TGFß/SMAD is multi-layered because of oncogenic and tumor suppressor long non-coding RNAs (LncRNAs). In this review, we have summarized most recent breakthroughs in our understanding related to regulation of TGFß/SMAD signaling by lncRNAs. We have comprehensively analyzed how different lncRNAs positively and negatively regulate TGFß/SMAD signaling in different cancers. We have gathered missing pieces of an incomplete jig-saw puzzle of lncRNA-interactome ranging from "sponge effects" of lncRNAs to mechanistic modulation of TGFß/SMAD signaling by lncRNAs.

Underlying causes of cerebral palsy: public health perspectives.

Cerebral palsy (CP) is a neurological pathology that is characterized by a combination of signs and symptoms that occur in neurodegenerative or metabolic disorder during the first few years of life. It is a complex pathology orchestrated by a plethora of different causes. The current diagnostic regimen for CP involves brain magnetic resonance imaging (MRI), and antenatal and perinatal insult. Despite advances in the field of genetics and molecular biology, the evaluating the underlying causes of this severe pathology are still bleak. In this review we have attempted to provide a landscape of the underlying mechanisms of cerebral palsy. We have partitioned this review broadly into genetic and proteomic-based studies, which have enriched our understanding about the pathogenesis of CP.

Vitamin C as an Anticancer Agent: Regulation of Signaling Pathways.

Treatment options for effective treatment of cancer with minimum off-target effects and maximum clinical outcomes have remained overarching goals in the clinical oncology. Vitamin C has remained in the shadows of controversy since the past few decades; burgeoning evidence has started to shed light on wide-ranging anticancer effects exerted by Vitamin C to induce apoptosis in drug-resistant cancer cells, inhibit uncontrolled proliferation of the cancer cells and metastatic spread. Landmark achievements in molecular oncology have ushered in a new era, and researchers have focused on the identification of oncogenic pathways regulated by Vitamin C in different cancers. However, there are visible knowledge gaps in our understanding related to the ability of Vitamin C to modulate a myriad of transduction cascades. There are scattered pieces of scientific evidence about promising potential of Vitamin C to regulate JAK-STAT, TGF/SMAD, TRAIL and microRNAs in different cancers. However, published data is insufficient and needs to be investigated comprehensively to enable basic and clinical researchers to reap full benefits and promote result-oriented transition of Vitamin C into various phases of clinical trials. In this review, we will emphasize on available evidence related to the regulation of oncogenic cell signaling pathways by Vitamin C in different cancers. We will also highlight the conceptual gaps, which need detailed and cutting-edge research.

Realizing the Potential of Blueberry as Natural Inhibitor of Metastasis and Powerful Apoptosis Inducer: Tapping the Treasure Trove for Effective Regulation of Cell Signaling Pathways.

Blueberries belong to the genus Vaccinium of the family Ericaceae. Rapidly accumulating experimentally verified data is uncovering the tremendous pharmacological properties of biologically active constituents of blueberries against different diseases. Our rapidly evolving knowledge about the multifaceted nature of cancer has opened new horizons to search for different strategies to target multiple effectors of oncogenic networks to effectively inhibit cancer onset and progression. Excitingly, whole blueberry powder and various bioactive constituents (pterostilbene, malvidin-3-galactoside) of blueberries have been shown to efficiently inhibit metastasis in animal models. These results are encouraging and future studies must focus on the identification of cell signaling pathways effectively modulated by blueberries in different cancers. It seems exciting to note that researchers are focusing on metastasis inhibitory effects of blueberry; however, to reap full benefits, it is necessary to take a step back and critically re-interpret the mechanisms used by active components of blueberry to inhibit or prevent metastasis. JAK/STAT, TGF/SMAD, Notch, SHH/GLI, and Wnt/ ß-Catenin have been shown to be directly involved in the regulation of metastasis. However, because of limited studies, it is difficult to critically assess the true potential of blueberry. Loss of apoptosis, metastasis and deregulation of signaling pathways are branching trajectories of molecular oncology. Accordingly, we have to emphasize on these essential facets to realistically claim blueberry as "Superfood". Different clinical trials have been conducted to gather clinical evidence about the chemopreventive role of blueberry or its bioactive components in cancer patients. But it seems clear that because of the lack of sufficient proof-of-concept studies, we cannot extract significant information about the transition of blueberry into the next phases of clinical trials. Overview of the existing scientific evidence revealed visible knowledge gaps and a better understanding of the targets of blueberry will be helpful in efficient and meaningful translation of laboratory findings to clinically effective therapeutics.

Recent updates on true potential of an anesthetic agent as a regulator of cell signaling pathways and non-coding RNAs in different cancers: Focusing on the brighter side of propofol.

There has always been a quest to search for synthetic and natural compounds having premium pharmacological properties and minimum off-target and/or side effects. Therefore, in accordance with this approach, scientists have given special attention to the molecules having remarkable ability to target oncogenic protein network, restore drug sensitivity and induce apoptosis in cancer cells. The mechanisms through which general anesthetics modulated wide-ranging deregulated cell signaling pathways and non-coding RNAs remained unclear. However, rapidly accumulating experimentally verified evidence has started to resolve this long-standing mystery and a knowledge about these important molecular targets has surfaced and how these drugs act at the molecular level is becoming more understandable. In this review we have given special attention to available evidence related to ability of propofol to modulate Wnt/ß-catenin, JAK/STAT and mTOR-driven pathway. Excitingly, great strides have been made in sharpening our concepts related to potential of propofol to modulate non-coding RNAs in different cancers. Collectively, these latest findings offer interesting, unexplored opportunities to target deregulated signaling pathways to induce apoptosis in drug-resistant cancers.

Regulation of signaling pathways by Ampelopsin (Dihydromyricetin) in different cancers: exploring the highways and byways less travelled.

Ampelopsin or Dihydromyricetin is gradually emerging as a high-quality natural product because of its ability to modulate wide-ranging signaling pathways. Ampelopsin (Dihydromyricetin) has been reported to effectively modulate growth factor receptor (VEGFR2 and PDGFRß) mediated signaling,  TRAIL/TRAIL-R pathway, JAK/STAT and mTOR-driven signaling in different cancers. Ampelopsin (Dihydromyricetin) has also been shown to exert inhibitory effects on the versatile regulators which trigger EMT (Epithelial-to-Mesenchymal Transition). Findings obtained from in-vitro studies are encouraging and there is a need to comprehensively analyze how Ampelopsin (Dihydromyricetin) inhibits tumor growth in different cancer models. Better knowledge of efficacy of Ampelopsin (Dihydromyricetin) in tumor bearing mice will be helpful in maximizing its translational potential.

Focusing on the brighter side of Sevoflurane: Realizing true potential of an anesthetic agent as a regulator of cell signaling pathways and microRNAs in different cancers.

Reconceptualization of different anesthetics as anticancer agents has opened new horizons for a better and sharper analysis of true potential of Sevoflurane as a promising and frontline candidate in the pipeline of anticancer agents. Sevoflurane mediated regulation of cell signaling pathways and non-coding RNAs has leveraged our understanding to another level. There have been remarkable advancements in unraveling mechanistic insights related to the ability of sevoflurane to modulate microRNAs in different cancers. Astonishingly, sevoflurane mediated regulation of miRNAs and long non-coding RNAs have been more comprehensively addressed in ischemia-reperfusion injuries. However, researchers yet have to gather missing pieces of premium research-work to uncover mechanistic regulation of long non-coding RNAs by sevoflurane in various cancers. Sevoflurane modulated control of miRNAs have been reported in glioma, colorectal cancer, breast cancer and hepatocellular carcinoma. In this review we have attempted to summarize most recent cutting edge and high-impact experimental researches which have elucidated myriad of underlying mechanisms modulated by sevoflurane to inhibit cancer development and progression. Despite some of the amazing pharmacological properties of sevoflurane, it has been shown to possess darker side because of its involvement in positive regulation of metastasis.  In accordance with this notion we have also summarized how sevoflurane enhanced migratory potential of different cancer cells in a separate section. Therefore, these aspects have to be tested in better designed experimental models to identify most relevant types of cancers which can be therapeutically targeted by sevoflurane.