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Topic Review
Mitochondria and Ageing
Declining mitochondrial function, reflected in defects in ATP synthesis and increased generation of toxic reactive oxygen species is a universal feature of natural ageing. It accompanies the other hallmarks of ageing which include progressive loss of function in multiple organs, sarcopenia and increasing maladaptive low-grade inflammation. These end in death, which is a cumulative result of loss of function, leading to either increased vulnerability to environmental hazards such as predation and disease or to failure of critical organ systems such as the heart, liver or kidney. Several processes that may contribute mechanistically to age related degeneration have been identified, including oxidative damage, accumulation of toxic protein aggregates, autoinflammatory processes, loss of stem cell populations and an increasing load of malfunctional senescent cells.  Mitochondrial dysfunction has connections with each of these processes.  The following is a brief overview of some of these connections.
  • 1.2K
  • 02 Nov 2020
Topic Review
Autophagy in Glioma
Abstract: Glioblastoma multiforme is the most malignant and aggressive type of brain neoplasm, with a mean life expectancy of less 15 months after diagnosis, despite a diversity of treatments, including surgery, radiation, chemotherapy, and immunotherapy. The resistance of GBM to various therapies is due to a highly mutated genome; these genetic changes induce a de-regulation of several signaling pathways and result in higher cell proliferation rates, angiogenesis, invasion, and a marked resistance to apoptosis; this latter trait is a hallmark of highly invasive tumor cells, such as glioma cells. Due to a defective apoptosis in gliomas, induced autophagic death can be an alternative to remove tumor cells. Paradoxically, however, autophagy in cancer can promote either a cell death or survival. Modulating the autophagic pathway as a death mechanism for cancer cells has prompted the use of both inhibitors and autophagy inducers. The autophagic process, either as a cancer suppressing or inducing mechanism in high-grade gliomas is discussed in this section.  
  • 1.4K
  • 02 Nov 2020
Topic Review
Dermal Fibroblasts
Scarring and regeneration are two physiologically opposite endpoints to skin injuries, with mammals, including humans, typically healing wounds with fibrotic scars. We aim to provide an updated review on fibroblast heterogeneity as determinants of the scarring–regeneration continuum. We discuss fibroblast-centric mechanisms that dictate scarring–regeneration continua with a focus on intercellular and cell–matrix adhesion. Improved understanding of fibroblast lineage-specific mechanisms and how they determine scar severity will ultimately allow for the development of antiscarring therapies and the promotion of tissue regeneration.
  • 1.4K
  • 30 Oct 2020
Topic Review
Human Neural Stem Cell Systems
       Building and functioning of the human brain requires the precise orchestration and execution of myriad molecular and cellular processes, across a multitude of cell types and over an extended period of time. Neural Stem Cells (NSCs) represent the heart of these processes, since they increase the pool of neural progenitors and are the founders of all the neural progeny which will constitute the adult human brain.
  • 1.4K
  • 30 Oct 2020
Topic Review
Breast cancer cell growth/motility is influenced by metal compounds
Triple-negative breast cancer (TNBC) is a  highly "aggressive" malignant neoplasm with limited treatment options due to the lack of expression of estrogen and progesterone receptors and HER2/neu. In search of novel molecules displaying anti-TNBC activities, the TNBC cell line MDA-MB231 was exposed to cadmium chloride and/or manganese chloride, and a biological characterization of the effect observed was performed. The data obtained demonstrate a cytotoxic effect exerted by cadmium chloride with drastic changes affecting gene expressions and production of reactive oxygen species. Conversely, manganese chloride was effective in increasing cell number and promoting cell invasive ability.  Such effect was reverted by coexposure with cadmium chloride. Thus, metal compounds appear to be able to modulate the biological behavior of TNBC cells, although addressing them to different fates. The data obtained suggest that high environmental pollution with manganese chloride might increase the risk of breast tumorigenesis. On the other hand, the restraining modulatory property of cadmium chloride looks promising and deserves a more detailed mechanistic study aimed to the identification of possible molecular targets instrumental in inhibiting the expansion of malignant breast cancer.
  • 1.3K
  • 30 Oct 2020
Topic Review
The origin cell of cancer
       Tumours may develop from stem cells as well as differentiated cells able to divide. Phenotypically, the two principal  types of cell of origin convert with the degree of genetic changes as the stem cell derived tumours stop earlier in the differentiation and the differentiated cells  gradually lose specific traits. However, the growth regulation of the cell of origin, which depends on its receptors conveying signals influencing proliferation, is essential in tumourigenesis since every cell division carries a small risk of mutation. Moreover, some normal cells have properties making them prone to develop into tumours as neuroendocrine cells which display low adherence as they occur spread by other cells, and also because they release signal substances affecting the vascular bed (for instance histamine).. Therefore, these cells may be the origin of tumours more malignant than apparent from their phenotype. Knowledge of the receptors of the cell of origin gives increased possibility to understand the tumourigenesis and also  improvement of prophylaxis and treatment of the tumours. Finally, spread of nearly normal tumour cells at an early phase gives a plausible explanation of quiescent tumor cell/dormant tumours.
  • 712
  • 30 Oct 2020
Topic Review
FTO Intronic SNP
Browning of white adipose tissue shifts adipocytes from energy storage white to energy expenditure beige types. The balance between the two adipocyte populations in white adipose tissue is highly determined by noncoding variants of the Fat mass and obesity-associated (FTO) locus which has the strongest association with obesity. The rs1421085 FTO risk allele results in a loss of ARID5B repression of IRX3 and IRX5 which promotes excess white adipocyte formation. Recent studies have revealed the presence of brown adipose tissues at several anatomical sites in humans including the deep-neck (DN).  We found that the characteristic gene expression profile and associated pathways of DN brown adipocytes were determined by partially overlapping effects of tissue site specific commitments of the stem cells, PPARγ stimulation and the FTO status of donors. The presence of FTO rs1421085 risk alleles had a strong influence, manifested during differentiation, on browning resulting in compromised expression of metabolic and mitochondrial genes as well as pathways which are decisive in thermogenesis.
  • 773
  • 30 Oct 2020
Topic Review
Aldosterone
Aldosterone is a steroid hormone that is produced in the adrenal cortex. Its major renal effect is to regulate electrolyte and water homeostasis in the distal tubule, thus maintaining blood pressure and extracellular fluid homeostasis through the activation of mineralocorticoid receptors (MR) in epithelial cells [2]. Aldosterone enters an epithelial cell and binds to the MR. The complex of aldosterone and MR translocates into the nucleus and regulates gene transcription of, among others, the epithelial sodium channel (ENaC) and the signaling proteins and kinases that impact channel and transporter activity, such as serum/glucocorticoid kinases (SGKs).
  • 1.8K
  • 30 Oct 2020
Topic Review
Monoubiquitin Signaling in Genetic Diseases
Ubiquitination is a reversible post-translational modification that controls protein function and stability. Different types of ubiquitination were described including polyubiquitination, the attachment of multiple ubiquitin residues, or monoubiquitination, the attachment of a single ubiquitin molecule. While most of the studies have described the role of polyubiquitination, recent evidences show that monoubiquitination is a key regulator of different cellular processes, including vesicular trafficking and protein complex formation and degradation. Enzymes regulating monoubiquitination such as E2 conjugating enzymes, E3 ligases or ubiquitin hydrolases, are found altered in several genetic diseases, including Parkinson's disease or Noonan syndrome.
  • 709
  • 29 Oct 2020
Topic Review
Cryptosporidium Parvum
Cryptosporidium parvum is a zoonotic intracellular protozoan responsible for the diarrheal illness cryptosporidiosis in humans and animals. Although a number of zoite surface proteins are known to be expressed during, and believed to be involved in, attachment and invasion of host cells, the molecular mechanisms by which C. parvum invades the host epithelial cells are not well understood. In the present study, we investigated the gene expression patterns, protein localization in developmental stages in culture, and in vitro neutralization characteristics of Cpgp40/15 and Cpgp40. Indirect immunoflfluorescence assay showed that Cpgp40/15 is associated with the parasitophorous vacuole membrane (PVM) during intracellular development. Both anti-gp40/15 and anti-gp40 antibodies demonstrated the ability to neutralize C. parvum infection in vitro. Further studies are needed to fully understand the specifific role and functional mechanism of Cpgp40/15 (or gp40/15 complex) in the invasion of the host or in the PVM and to determine the feasibility of gp40/15 as a vaccine candidate for cryptosporidiosis in vivo.
  • 785
  • 29 Oct 2020
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