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Topic Review
Cyclotide Scaffold for Drug Development
Cyclotides are a novel class of micro-proteins (≈30–40 residues long) with a unique topology containing a head-to-tail cyclized backbone structure further stabilized by three disulfide bonds that form a cystine knot. This unique molecular framework makes them exceptionally stable to physical, chemical, and biological degradation compared to linear peptides of similar size. The cyclotides are also highly tolerant to sequence variability, aside from the conserved residues forming the cystine knot, and are orally bioavailable and able to cross cellular membranes to modulate intracellular protein–protein interactions (PPIs), both in vitro and in vivo. These unique properties make them ideal scaffolds for many biotechnological applications, including drug discovery. 
  • 639
  • 13 Aug 2021
Topic Review
Biological Clock in Liver Cancer
The biological clock controls at the molecular level several aspects of mammalian physiology, by regulating daily oscillations of crucial biological processes such as nutrient metabolism in the liver. Disruption of the circadian clock circuitry has recently been identified as an independent risk factor for cancer and classified as a potential group 2A carcinogen to humans. Hepatocellular carcinoma (HCC) is the prevailing histological type of primary liver cancer, one of the most important causes of cancer-related death worldwide. HCC onset and progression is related to B and C viral hepatitis, alcoholic and especially non-alcoholic fatty liver disease (NAFLD)-related milieu of fibrosis, cirrhosis, and chronic inflammation.
  • 487
  • 13 Aug 2021
Topic Review
CD147
Microenvironment plays a crucial role in tumor development and progression. Cancer cells modulate the tumor microenvironment, which also contribute to resistance to therapy. Identifying biomarkers involved in tumorigenesis and cancer progression represents a great challenge for cancer diagnosis and therapeutic strategy development. CD147 is a glycoprotein involved in the regulation of the tumor microenvironment and cancer progression by several mechanisms—in particular, by the control of glycolysis and also by its well-known ability to induce proteinases leading to matrix degradation, tumor cell invasion, metastasis and angiogenesis. 
  • 863
  • 12 Aug 2021
Topic Review
NO Signaling Pathways in Aging
Nitric Oxide (NO) is a potent signaling molecule involved in the regulation of various cellular mechanisms and pathways under normal and pathological conditions. NO production, its effects, and its efficacy, are extremely sensitive to aging-related changes in the cells. 
  • 455
  • 12 Aug 2021
Topic Review
Photoimmunotherapy of Ovarian Cancer
Ovarian cancer (OvCa) is the leading cause of gynecological cancer-related deaths in the United States, with five-year survival rates of 15–20% for stage III cancers and 5% for stage IV cancers. The standard of care for advanced OvCa involves surgical debulking of disseminated disease in the peritoneum followed by chemotherapy. Despite advances in treatment efficacy, the prognosis for advanced stage OvCa patients remains poor and the emergence of chemoresistant disease localized to the peritoneum is the primary cause of death. Therefore, a complementary modality that is agnostic to typical chemo- and radio-resistance mechanisms is urgently needed. Photodynamic therapy (PDT), a photochemistry-based process, is an ideal complement to standard treatments for residual disease. The confinement of the disease in the peritoneal cavity makes it amenable for regionally localized treatment with PDT. PDT involves photochemical generation of cytotoxic reactive molecular species (RMS) by non-toxic photosensitizers (PSs) following exposure to non-harmful visible light, leading to localized cell death. However, due to the complex topology of sensitive organs in the peritoneum, diffuse intra-abdominal PDT induces dose-limiting toxicities due to non-selective accumulation of PSs in both healthy and diseased tissue. In an effort to achieve selective damage to tumorous nodules, targeted PS formulations have shown promise to make PDT a feasible treatment modality in this setting. This targeted strategy involves chemical conjugation of PSs to antibodies, referred to as photoimmunoconjugates (PICs), to target OvCa specific molecular markers leading to enhanced therapeutic outcomes while reducing off-target toxicity. 
  • 549
  • 12 Aug 2021
Topic Review
Nanomaterials as Inhibitors in EMT
Epithelial-mesenchymal transition (EMT) has emerged as a key regulator of cell invasion and metastasis in cancers. However, although EMT represents a relevant therapeutic target for cancer treatment, its application in the clinic is still limited due to various reasons, including appropriate drug delivery. Different nanomaterials may be used to counteract EMT induction, providing novel therapeutic tools against many different cancers. We discuss the application of various nanomaterials for EMT-based therapies in cancer, the therapeutic relevance of some of the proposed EMT targets, and the potential benefits and weaknesses of each approach.
  • 551
  • 11 Aug 2021
Topic Review
Carotenoids in Age-Related Macular Degeneration
Age-related macular degeneration (AMD) remains a leading cause of modifiable vision loss in older adults. Chronic oxidative injury and compromised antioxidant defenses represent essential drivers in the development of retinal neurodegeneration. Overwhelming free radical species formation results in mitochondrial dysfunction, as well as cellular and metabolic imbalance, which becomes exacerbated with increasing age. Thus, the depletion of systemic antioxidant capacity further proliferates oxidative stress in AMD-affected eyes, resulting in loss of photoreceptors, neuroinflammation, and ultimately atrophy within the retinal tissue.
  • 875
  • 11 Aug 2021
Topic Review
Maternal Selenium and Developmental Programming
Selenium (Se) is an essential trace element of fundamental importance to health due to its antioxidant, anti-inflammatory, and chemopreventive properties, attributed to its presence within at least 25 selenoproteins (Sel).
  • 529
  • 11 Aug 2021
Topic Review
Heme Burden and Kidney
As it pertains to the kidney, several clinical conditions have been recognized that are associated with significant amount of free heme and subsequent kidney damage. The kidney is frequently involved during clinical settings, with the common denominator of increased heme burden given its primary function of filtration. Moreover, the proximal tubules possess a high number of mitochondria that upon injury release their cytochrome heme content leading to higher levels of local heme and hence potentiating the cycle of injury.
  • 560
  • 11 Aug 2021
Topic Review
Endoscopic Papillary Abnormalities and EPSR
The increasing efficiency of the different lasers and the improved performance of endoscopic devices have led to smaller stone fragments that impact the accuracy of microscopic evaluation (morphological and infrared). Before the stone destruction, the urologist has the opportunity to analyze the stone and the papillary abnormalities endoscopically (endoscopic papillary recognition (EPR) and endoscopic stone recognition (ESR)). Our objective was to evaluate the value for those endoscopic descriptions.
  • 427
  • 10 Aug 2021
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