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Topic Review
Biography
Topic Review
Challenges in Adoptive T Cell Therapy for AML
Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed-refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything, considering only around 30% of patients show a response but with consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. Below information first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML.
414
29 May 2023
Topic Review
Anti-RAS-p21 Peptides from Expression Libraries
X-ray crystallographic structures of wild-type and oncogenic RAS-p21 bound to GDP and GTP suggested that there is an absence of surface-exposed clefts to which drug molecules can bind, suggesting that RAS-p21 may be “undruggable”. This impression has proved false by a series of studies that have resulted in a number of cyclic peptides and small molecules that bind to mutant RAS-p21 proteins in their switch 2 domains in a binding “pocket” involving the switch 2 loop (residues 55–67) and the α-2 helix (residues 67–73). This binding is very much dependent on the specific amino acid substitutions that occur. When these agents bind, they strongly inhibit either GTP-bound RAS-p21 or GDP-RAS-p21. In the former case, GTP-bound RAS-p21 cannot bind to the RBD of ras, and in the latter case, GDP-bound RAS-p21 is “frozen” in an inactivated state such that it cannot exchange GDP for GTP and, since it cannot bind to GTP, it cannot adopt an activated conformation in which it presumably interacts with RAF.
503
29 May 2023
Topic Review
Plasma Clearance Receptors of FVIII and VWF
Congenital deficiency in blood coagulation factor (F) VIII (FVIII) results in excessive bleeding. The disease (hemophilia A) is treated with infusions of therapeutic FVIII concentrates, either plasma-derived (pdFVIII) or produced with recombinant DNA technology (rFVIII). Due to the relatively short FVIII plasma half-life (~12 h), such treatment requires frequent FVIII infusions (3–4 per week in prophylaxis) that calls for developing more efficient longer-acting FVIII products, in particular with an extended plasma lifetime, commonly termed half-life (EHL). Relevant protein modifications are performed via genetic and/or chemical modification of rFVIII, and efficient designs require understanding the molecular mechanisms of FVIII plasma clearance.
409
29 May 2023
Topic Review
PGPB and Microalgae for Restoration of Degraded Soil
Plant-growth-promoting bacteria (PGPB) are bacterial strains isolated from diverse environments with the potential to positively influence the growth and yield of diverse plants, mostly of agricultural importance. Microalgae (including cyanobacteria) and PGPB can be used as promoters of soil recovery.
340
29 May 2023
Topic Review
Bone Regeneration Medicine
Bone regenerative medicine is a clinical approach combining live osteoblast progenitors, such as mesenchymal stromal cells (MSCs), with a biocompatible scaffold that can integrate into host bone tissue and restore its structural integrity.
286
29 May 2023
Topic Review
Liposomes-Based Drug Delivery Systems of Anti-Biofilm Agents
All currently approved antibiotics are being met by some degree of resistance by the bacteria they target. Biofilm formation is one of the crucial enablers of bacterial resistance, making it an important bacterial process to target for overcoming antibiotic resistance. Accordingly, several drug delivery systems that target biofilm formation have been developed. One of these systems is based on lipid-based nanocarriers (liposomes), which have shown strong efficacy against biofilms of bacterial pathogens. Liposomes come in various types, namely conventional (charged or neutral), stimuli-responsive, deformable, targeted, and stealth. This research reviews studies employing liposomal formulations against biofilms of medically salient gram-negative and gram-positive bacterial species reported recently.
384
29 May 2023
Topic Review
Cryptococcus neoformans/C. gattii
Complex
The epidemiology of the Cryptococcus species complex (SC) is well known and briefly summarized below. Among these species, most clinical isolates are C. neoformans; C. gattii has been isolated in the U.S., mostly in the Pacific Northwest area.
352
29 May 2023
Topic Review
Protein–DNA Interactions in Human Papillomavirus
Human papillomavirus (HPV) is a group of alpha papillomaviruses that cause various illnesses, including cancer. There are more than 160 types of HPV, with many being “high-risk” types that have been clinically linked to cervical and other types of cancer. “Low-risk” types of HPV cause less severe conditions, such as genital warts. Numerous studies have shed light on how HPV induces carcinogenesis. The HPV genome is a circular double-stranded DNA molecule that is approximately 8 kilobases in size. Replication of this genome is strictly regulated and requires two virus-encoded proteins, E1 and E2. E1 is a DNA helicase that is necessary for replisome assembly and replication of the HPV genome. On the other hand, E2 is responsible for initiating DNA replication and regulating the transcription of HPV-encoded genes, most importantly the E6 and E7 oncogenes.
391
29 May 2023
Topic Review
Impact of Wort Amino Acids on Beer Flavour
The process by which beer is brewed has not changed significantly since its discovery thousands of years ago. Grain is malted, dried, crushed and mixed with hot water to produce wort. Yeast is added to the sweet, viscous wort, after which fermentation occurs. The biochemical events that occur during fermentation reflect the genotype of the yeast strain used, and its phenotypic expression is influenced by the composition of the wort and the conditions established in the fermenting vessel. Although wort is complex and not completely characterized, its content in amino acids indubitably affects the production of some minor metabolic products of fermentation which contribute to the flavour of beer.
623
29 May 2023
Topic Review
Mitochondria in Health and Disease
Mitochondrial alterations have been implicated in a wide range of diseases, such as neurodegenerative disorders, metabolic disorders, and cancer.
459
29 May 2023
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