Type I diabetes is characterized by the gradual loss of β cells in the pancreas leading to insulin deficiency, hyperglycemia, and if left untreated, death. Since the 1920’s Type I diabetes has been treated with multiple daily injections of insulin in an attempt to restore glucose metabolism and stave off ketoacidosis - the life-threatening consequence of chronic hyperglycemia. While insulin injections have allowed millions of people to successfully live with Type I diabetes, it is by no means a perfect treatment. Multiple daily injections and the short half-life of insulin combine to cause daily bouts of hypoglycemia and hyperglycemia, which can cause multiple detrimental sequelae including microvascular damage, nerve damage, fat buildup/obesity, and cardiovascular disease (Smith-Marsh and Zeller 2017). Thus, Type I diabetics have been waiting for a new and better therapy to be developed.
Recent studies have demonstrated that leptin can prolong life chronically in rats with poorly-controlled type 1 diabetes (T1D). Multiple explanations have been proposed to explain leptin’s chronic antihyperglycemic effect, including suppression of glucagon release and/or signaling, reductions in hyperphagia and ectopic lipid content, and improvements in insulin sensitivity; it is leptin’s ability to reduce plasma glucose relies on all of these effects. In addition, leptin reverses hyperglycemia and diabetic ketoacidosis (DKA) acutely, within 6 hours of leptin infusion, by suppressing hypothalamic-pituitary-adrenal (HPA) axis activity in insulinopenic rats. Thus current evidence suggests that leptin’s acute, insulin-independent effect to reverse DKA by suppressing HPA axis activity occurs through a different mechanism from its chronic, pleotropic, insulin-dependent effect to reverse hyperglycemia and prolong survival in rodents with T1D. Leptin may therefore represent an attractive therapeutic target to improve glycemic control in humans with poorly-controlled T1D.
Cancer is a highly heterogeneous disease and each cancer has its individual metabolic fingerprint. Even within a single cancer, its constituent cells are heterogeneous and the metabolic fingerprint varies from one cell to another (Jie Zheng 2012). Unlike normal cells, glycolysis is enhanced in cancer cells (Warburg 1927, 1956; Robert A. Gatenby et.al. 2004; Jie Zheng 2012). This was first described by German scientist Otto Warburg in the 1920s. Following Warburg’s observations that cancer cells have a higher rate of glycolysis than normal cells, interest in the metabolic property of cancers has steadily increased. In recent years, understanding the features and complexity of the metabolism and energetics of cancer cells has been rekindled, mainly because therapy targeting metabolism hits the “core” of the cancer and has the potential to cripple a cancer cell’s ability to self-renew.
Glycolysis is highly upregulated in head and neck squamous cell carcinoma (HNSCC). HNSCC glycolysis is an important contributor to disease progression and decreases sensitivity to radiation or chemotherapy. Despite therapeutic advances, the survival rates for HNSCC patients remain low. Understanding glycolysis regulation in HNSCC will facilitate the development of effective therapeutic strategies for this disease. In this review, we will evaluate the regulation of altered HNSCC glycolysis and possible therapeutic approaches by targeting glycolytic pathways.
Cellular communication is an important process for animal development, which guides cell fate specification and the movement of cells within and between tissues. During growth, cell-cell communication plays a critical role in decisions that determine whether cells survive to contribute to the organism. Cell competition is one such remarkable phenomenon that is conserved from invertebrate to mammals, that causes the elimination of relatively less fit cells from tissues, helping to maintain overall tissue health. Cell competition is not only functional during development but it also replaces less fit cells in adult tissues. This suggests that the properties of individual cells are monitored and that variant clones of progenitor cells can be favored or eliminated accordingly. Progress has been made in recent years to understand the mechanisms of cell competition by several approaches but still much remains to be learned. Cell competition has been implicated in regenerative medicine, cancer and aging. It was assumed that molecular signals between cells are necessary and sufficient for cell competition. However, recent reports illustrate an interesting mechanism that has been previously speculated but never proven. In this review, we will discuss the process of cell competition and its’ implications and mechanisms.
In recent years, biology has steadily become a more interdisciplinary field. Advances in technology have pioneered the development of many tools that allow concepts in physics, math, computer science, and chemistry to be applied to biological problems. As an example, next generation sequencing (NGS) technologies have been rapidly developed with these tools becoming more and more accessible to biologists. NGS is also known as high-throughput sequencing and is an all-inclusive term used to describe modern sequencing technologies including Illumina, 454, Ion torrent, and SOLiD sequencing that can generate billions of reads. With the advent of NGS and big data, many biological quandaries ranging from the microbiome to human population studies can now be explored in ways that were not previously possible.
Conventional microbiological methods have been readily taken over by newer molecular techniques due to the ease of use, reproducibility, sensitivity and speed of working with nucleic acids. These tools allow high throughput analysis of complex and diverse microbial communities, such as those in soil, freshwater, saltwater, or the microbiota living in collaboration with a host organism (plant, mouse, human, etc). For instance, these methods have been robustly used for characterizing the plant (rhizosphere), animal and human microbiome specifically the complex intestinal microbiota. The human body has been referred to as the Superorganism since microbial genes are more numerous than the number of human genes and are essential to the health of the host. In this review we provide an overview of the Next Generation tools currently available to study microbial ecology, along with their limitations and advantages.
L-proline, a natural α-amino acid, has been found useful as an osmoprotectant and antioxidant. It can prevent the denaturation of peptides and increase the survival rate of freeze-dried fungi by inhibiting the generation of intracellular reactive oxygen species. L-proline was shown to effectively preserve the structure and function of the frozen vesicles. But there is evidence showing that L-proline was able to destabilize the lamellar liquid-crystalline phases in both fully hydrated and freeze-dried lipids, which is undesirable. Given the complex role of L-proline in the stabilization of biologics, the current study conducted molecule dynamics simulations of hydrated 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers in the presence of L-proline to elucidate the interactions between L-proline and lipid bilayers. The results show that the proline molecules can slightly perturb lipid headgroups with an occasional insert of proline molecules between lipid headgroups. In the fully hydrated state, proline molecules prefer to hydrogen-bond with water molecules rather than lipids. The MD simulation results do not support the 'water replacement' hypothesis for the mechanism of membrane protection by proline.
Despite continued scientific research efforts and technological advancement to find an effective cure, Cancer remains an enigma. This article aims to propose a different scientific approach to studying the biology of Cancer by offering insights into the striking similarities between the psyche of humans and the behavior of cancer cells. Without attempting to trivialize the complexity of the disease, the article will discuss the fundamental connection between humans and cells that extend beyond just signaling pathways and molecular bonds. The discussion will introduce Cancer Cell Psychology as a new area of study that should be closely considered to further our understanding of this disease.
The dynamic interplay between resident microbiota, host immunity and anti-cancer therapy has generated a captivating enigma underlying the assignment of cause-effect relationships among these factors. The diverse effects of microbes on carcinogenesis, ranging from preventing or promoting cancer to dictating therapeutic outcomes, complicates the understanding of the relationship between the microbiota and the host. Understanding how host-microbe interactions are influenced by genes and environment in carcinogenesis, and applying that knowledge for cancer detection and treatment are gathering prime interest. This review scrutinizes the host-microbe relationship in the context of cancer by discussing the latest findings involving the host-microbe-drug interaction axes.