Regulation of Cell Signaling Pathways and miRNAs by Resveratrol in Different Cancers

Genomic and proteomic studies have helped improve our understanding of the underlying mechanism(s) of cancer development and progression. Mutations, overexpressed oncogenes, inactivated/downregulated tumor suppressors, loss of apoptosis, and dysregulated signal transduction cascades are some of the well-studied areas of research. Resveratrol has gained considerable attention in the last two decades because of its pleiotropic anticancer activities. In this review, we have summarized the regulation of WNT, SHH (sonic hedgehog)/GLI (glioma-associated oncogene homolog), TGFβ1 (transforming growth factor beta 1)/SMAD, NOTCH, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), STAT (signal transducer and activator of transcription), and microRNAs by resveratrol in different cancers. The importance of these signaling pathways in cancer progression, along with their modulation by resveratrol, is discussed. Further, we also evaluate the mechanisms and implications of the downregulation of oncogenic miRNAs and the upregulation of tumor suppressor miRNAs by resveratrol, both of which also define its ability to inhibit tumor growth and metastasis. It is envisioned that designing effective clinical trials will be helpful for the identification of resveratrol responders and non-responders and the elucidation of how this phytochemical can be combined with current therapeutic options to improve their clinical efficacy and reduce off-target effects

Effects of SLC22A2 (rs201919874) and SLC47A2 (rs138244461) genetic variants on Metformin Pharmacokinetics in Pakistani T2DM patients

Objective: To determine the frequencies of single nucleotide polymorphisms rs201919874 and rs138244461 in genes SLC22A2 and SLC47A2 respectively in Pakistani diabetes patients in order to characterise the genetic variants and determine their association with the pharmacokinetics of metformin. Methods: The case-control study was conducted at the International Islamic University, Islamabad, Pakistan, from June 2016 to June 2017, and comprised genotypes of diabetic cases and matching controls which were determined following allele-specific polymerase chain reaction. Cases were further divided into Group A and Group B. The former consisted of diabetics who were on monotherapy of metformin, while the latter consisted of diabetics treated with a combination of metformin and sulfonylureas. In-silico analysis was performed to verify the effect of single nucleotide polymorphisms rs201919874 and rs138244461 on the structure of genes. Association was statistically determined using SPSS 18. Results: Of the 1200 subjects, 800(66.6%) were cases and 400(33.3%) were controls. Among the cases, 400(50%) each were in Group A and Group B. Significant difference was observed in the distribution of rs201919874 between Group A and controls (p<0.05) and between Group B and controls (p<0.05) for heterozygous genotypic frequency and for allelic frequency. Conversely, statistically significant difference was observed in rs138244461 (p<0.05) for all genotypic and allelic frequencies. Genotypes were significantly associated with glycated haemoglobin, random and fasting glucose levels in Group A compared to Group B (p<0.05). In-silico analysis showed that both single nucleotide polymorphisms were expected to create significantly damaging structural changes in domains and helix (p<0.05 each). Conclusions: Both exonic single nucleotide polymorphisms were found to be associated with the pharmacokinetics of metformin

Regulation of cancer cell signaling pathways by mushrooms and their bioactive molecules: Overview of the journey from benchtop to clinical trials

Mushrooms represent a tremendous source of biologically useful and pharmacologically active molecules. Recent breakthroughs in cancer genetics, genomics, proteomics and translational research have helped us to develop a better understanding of the underlying mechanisms which are contributory in cancer development and progression. Different signaling pathways particularly, Wnt, SHH, TGF/SMAD and JAK/STAT have been shown to modulate cancer progression and development. Increasingly it is being realized that genetic/epigenetic mutations and loss of apoptosis also mandate a 'multi-molecular' perspective for the development of therapies to treat cancer. In this review we attempted to provide an overview of the regulation of different signaling pathways by mushrooms and their bioactive compounds. Regulation of Wnt and JAK-STAT pathways by mushrooms is deeply studied but we do not have comprehensive information about regulation of TGF/SMAD, Notch and TRAIL induced signaling pathways because of superficially available data. There are outstanding questions related to modulation of oncogenic and tumor suppressor microRNAs by mushrooms in different cancers. Therefore, detailed mechanistic insights related to targeting of multiple pathways by extracts or bioactive compounds from mushrooms will be helpful in bridging our current knowledge gaps and translation of medicinally precious bioactive molecules to clinically effective therapeutics

Bitter gourd (Momordica charantia) as a rich source of bioactive components to combat cancer naturally: Are we on the right track to fully unlock its potential as inhibitor of deregulated signaling pathways

Research over decades has progressively explored pharmacological actions of bitter gourd (Momordica charantia). Biologically and pharmacologically active molecules isolated from M. charantia have shown significant anti-cancer activity in cancer cell lines and xenografted mice. In this review spotlight was set on the bioactive compounds isolated from M. charantia that effectively inhibited cancer development and progression via regulation of protein network in cancer cells. We summarize most recent high-quality research work in cancer cell lines and xenografted mice related to tumor suppressive role-play of M. charantia and its bioactive compounds. Although M. charantia mediated health promoting, anti-diabetic, hepatoprotective, anti-inflammatory effects have been extensively investigated, there is insufficient information related to regulation of signaling networks by bioactive molecules obtained from M. charantia in different cancers. M. charantia has been shown to modulate AKT/mTOR/p70S6K signaling, p38MAPK-MAPKAPK-2/HSP-27 pathway, cell cycle regulatory proteins and apoptosis-associated proteins in different cancers. However, still there are visible knowledge gaps related to the drug targets in different cancers because we have not yet developed comprehensive understanding of the M. charantia mediated regulation of signal transduction pathways. To explore these questions, experimental platforms are needed that can prove to be helpful in getting a step closer to personalized medicine

Regulation of Cell Signaling Pathways by Berberine in Different Cancers: Searching for Missing Pieces of an Incomplete Jig-Saw Puzzle for an Effective Cancer Therapy

There has been a renewed interest in the identification of natural products having premium pharmacological properties and minimum off-target effects. In accordance with this approach, natural product research has experienced an exponential growth in the past two decades and has yielded a stream of preclinical and clinical insights which have deeply improved our knowledge related to the multifaceted nature of cancer and strategies to therapeutically target deregulated signaling pathways in different cancers. In this review, we have set the spotlight on the scientifically proven ability of berberine to effectively target a myriad of deregulated pathways

Developing future heat-resilient vegetable crops

Climate change seriously impacts global agriculture, with rising temperatures directly affecting the yield. Vegetables are an essential part of daily human consumption and thus have importance among all agricultural crops. The human population is increasing daily, so there is a need for alternative ways which can be helpful in maximizing the harvestable yield of vegetables. The increase in temperature directly affects the plants’ biochemical and molecular processes; having a significant impact on quality and yield. Breeding for climate-resilient crops with good yields takes a long time and lots of breeding efforts. However, with the advent of new omics technologies, such as genomics, transcriptomics, proteomics, and metabolomics, the efficiency and efficacy of unearthing information on pathways associated with high-temperature stress resilience has improved in many of the vegetable crops. Besides omics, the use of genomics-assisted breeding and new breeding approaches such as gene editing and speed breeding allow creation of modern vegetable cultivars that are more resilient to high temperatures. Collectively, these approaches will shorten the time to create and release novel vegetable varieties to meet growing demands for productivity and quality. This review discusses the effects of heat stress on vegetables and highlights recent research with a focus on how omics and genome editing can produce temperature-resilient vegetables more efficiently and faster

MiRNAs and their interplay with PI3K/AKT/mTOR pathway in ovarian cancer cells. a potential role in platinum resistance

Ovarian cancer is a leading cause of death among gynecologic malignancies. This disappointing prognosis is closely related to intrinsic or acquired resistance to conventional platinum-based chemotherapy, which can affect a third of patients. As such, investigating relevant molecular targets is crucial in the fight against this disease. So far, many mutations involved in ovarian cancer pathogenesis have been identified. Among them, a few pathways were implicated. One such pathway is the P13K/AKT/mTOR with abnormalities found in many cases. This pathway is considered to have an instrumental role in proliferation, migration, invasion and, more recently, in chemotherapy resistance. Many miRNAs have been found to influence P13K/AKT/mTOR pathway with different potential role in tumor genesis and ovarian cancer behaviour. In particular, their biological function was recently investigated as regards chemoresistance, therefore, leading to the identification of potential specific indirect biomarker of platinum sensitivity in ovarian cancer