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Topic Review
α-Lipoic Acid
α-lipoic acid (ALA, thioctic acid) is an organosulfur component produced from plants, animals, and humans. It has various properties, among them great antioxidant potential and is widely used as a racemic drug for diabetic polyneuropathy-associated pain and paresthesia. Naturally, ALA is located in mitochondria, where it is used as a cofactor for pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase complexes. Despite its various potentials, ALA therapeutic efficacy is relatively low due to its pharmacokinetic profile. Data suggests that ALA has a short half-life and bioavailability (about 30%) triggered by its hepatic degradation, reduced solubility as well as instability in the stomach. However, the use of various innovative formulations has greatly improved ALA bioavailability. The R enantiomer of ALA shows better pharmacokinetic parameters, including increased bioavailability as compared to its S enantiomer. Indeed, the use of amphiphilic matrices has capability to improve ALA bioavailability and intestinal absorption. 
  • 674
  • 29 Jul 2021
Topic Review
α-Lactalbumin
α-Lactalbumin (α-LA) is a small (Mr 14,200), acidic (pI 4-5), Ca2+-binding protein. α-LA is a regulatory component of lactose synthase enzyme system. α-LA is very important in infant nutrition since it constitutes a large part of the whey and total protein in human milk. The protein possesses a single strong Ca2+-binding site, which can also bind Mg2+, Mn2+, Na+, K+, and some other metal cations. It contains several distinct Zn2+-binding sites. Physical properties of α-LA strongly depend on the occupation of its metal binding sites by metal ions. In the absence of bound metal ions α-LA is in the molten globule-like state. The binding of metal ions, and especially of Ca2+, increases stability of α-LA against action of heat, various denaturing agents, and proteases, while the binding of Zn2+ to the Ca2+-loaded protein decreases its stability and causes its aggregation. The thermal unfolding of apo-α-LA takes place in the temperature region from 10 to 30 °C. The binding of Ca2+ under the conditions of low ionic strength shifts the thermal transition to higher temperatures by more than 40 °C. The binding of Mg2+, Na+, and K+ increases protein stability as well. The stronger an ion binds to the protein, the more pronounced the thermal transition shift. All four classes of surfactants (anionic, cationic, non-ionic, and zwitterionic) denature α-LA and the denaturation involves at least one intermediate. The position of any denaturation transition in α-LA (half-transition temperature, half-transition pressure, half-transition denaturant concentration) depends upon metal ion concentration in solution (especially if this metal ion is Ca2+). Therefore, values of denaturation temperature or urea or guanidine hydrochloride denaturing concentration are relatively meaningless for α-LA without specifying the metal ion content(s) and their solution concentration(s). At a neutral or slightly acidic pH at a physiological temperature, α-LA can associate with membranes. The conformations of the membrane-bound protein range from native-like to molten globule-like states. At a low pH, α-LA penetrates the interior of the negatively charged membranes and exhibits a molten globule conformation. Depending on external conditions, α-LA can form amyloid fibrils, amorphous aggregates, nanoparticles, and nanotubes. At pH 2, α-LA in the classical molten globule conformation can form amyloid fibrils. Some of these aggregated states of α-LA (nanoparticles, nanotubes) can be used in practical applications such as drug delivery to tissues and organs. The structure and self-assembly behavior of α-LA are governed by a subtle balance between hydrophobic and polar interactions and this balance can be finely tuned through the addition of selected substances. Small size nanoparticles of α-LA (100 to 200 nm) can be obtained with the use of various desolvating agents. Partially hydrolyzed α-LA can form nanotubes. α-LA and some of its fragments possess bactericidal and antiviral activities. Complexes of partially unfolded α-LA with oleic acid showed significant cytotoxicity to various tumor and bacterial cells. α-LA in such complexes plays a role of a delivery carrier of cytotoxic fatty acid molecules into tumor cells across the cell membrane. Cytotoxic protein–oleic acid complexes possess a common core-shell structure, where an oily core is made of a micellar oleic acid, whereas a proteinaceous shell, which stabilizes the oleic acid micelle, is formed from the flexible, partially unfolded proteins. These complexes called liprotides (lipids and partially denatured proteins), which are potential novel anti-tumorous drugs, can be considered as molten globular containers filled with the toxic oil.
  • 1.6K
  • 31 Aug 2020
Topic Review
α-Helices in the T3SEs
Type III Secretion Systems (T3SSs) are multicomponent nanomachines located at the cell envelope of Gram-negative bacteria. Their main function is to transport bacterial proteins either extracellularly or directly into the eukaryotic host cell cytoplasm. Type III Secretion effectors (T3SEs), latest to be secreted T3S substrates, are destined to act at the eukaryotic host cell cytoplasm and occasionally at the nucleus, hijacking cellular processes through mimicking eukaryotic proteins. T3SE families adopt novel folds to target eukaryotic functions. These folds comprise a high helical content, which possibly reflects the specific requirements from T3SS effectors. In particular, effectors must (i) be able to be easily unfolded, (ii) cross the narrow T3S channel, (iii) be highly folded as soon as they will be found inside the host cell, in order to evade the host defense mechanisms, and (iv) display functional competence and structural plasticity in their final destination. α-helices can optimally fulfil these requirements.
  • 540
  • 06 Jun 2021
Topic Review
α Cell in Diabetes Pathogenesis
The involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon’s secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans’ islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (β) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to β cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (KATP) opening have also been linked to glucagon hypersecretion. 
  • 382
  • 27 Oct 2021
Topic Review
Zwitterionic Dental Biomaterials
Biofilms are formed on surfaces inside the oral cavity covered by the acquired pellicle and develop into a complex, dynamic, microbial environment. Oral biofilm is a causative factor of dental and periodontal diseases. Accordingly, novel materials that can resist biofilm formation have attracted significant attention. Zwitterionic polymers (ZPs) have unique features that resist protein adhesion and prevent biofilm formation while maintaining biocompatibility. Recent literature has reflected a rapid increase in the application of ZPs as coatings and additives with promising outcomes. 
  • 5.7K
  • 29 Dec 2020
Topic Review
Zuotin-Related Factor 1
Recently, Zuotin-related factor 1 (ZRF1), an epigenetic regulator, was found to be involved in transcriptional regulation. In animals and humans, ZRF1 specifically binds to monoubiquitinated histone H2A through a ubiquitin-binding domain and derepresses Polycomb target genes at the beginning of cellular differentiation. In addition, ZRF1 can work as a tumor suppressor. According to bioinformatics analysis, ZRF1 homologs are widely found in plants.
  • 596
  • 18 Aug 2021
Topic Review
Zoos as Conservation Institutions
Zoological institutions, which were once exclusively for entertainment, are now leaders of wildlife conservation. This centuries-long transition was punctuated by key milestones that reformed wild animal exploitation into a mission of protection. Modern zoos perform ex situ activities to preserve natural resources, which are enabled by the housing of wild species. Zoo-managed animals facilitate new scientific knowledge, public education, and strategic breeding to maintain genetic diversity.
  • 444
  • 30 Nov 2023
Topic Review
Zoopharmacology
Zoopharmacognosy is the multidisciplinary approach of the self-medication behavior of many kinds of animals. Recent studies showed the presence of antitumoral secondary metabolites in some of the plants employed by animals and their use for the same therapeutic purposes in humans. Other related and sometimes confused term is Zootherapy, which consists on the employment of animal parts and/or their by-products such as toxins, venoms, etc., to treat different human ailments. Therefore, the aim of this work is to provide a brief insight for the use of Zoopharmacology (comprising Zoopharmacognosy and Zootherapy) as new paths to discover drugs studying animal behavior and/or using compounds derived from animals.
  • 714
  • 28 Jun 2021
Topic Review
Zoonotic Visceral Leishmaniasis: Blood Macrophages and Kupffer Cells
Leishmania infantum is a parasite that causes zoonotic visceral leishmaniasis, a disease that affects humans, wild and domestic animals, mainly domestic dogs. Macrophages are cells of the immune system, existing in the peripheral blood and associated with different tissues in the mammal body, having the task to protect against microbiological threats. Interestingly, Leishmania can manipulate the macrophages into a non-active ghost-like state, allowing the parasite to stay in the host. The liver, which is a vital organ and a target for the parasite, has a resident population of macrophages designated as Kupfer cells. Therefore, a better understanding of the immune mechanisms exhibited by the macrophages when facing Leishmania parasite is needed to improve control strategies.
  • 422
  • 13 Jan 2022
Topic Review
Zoo Food Preparation and Presentation
From its foundations in agricultural science, zoo animal nutrition has developed into a biologically informed, evidence-based discipline. However, some facets of nutrition still make use of a more traditional approach, such as the field of zoo presentation. For example, it is common practice to prepare animal diets by chopping them into bite-size chunks, yet there is limited peer-reviewed evidence that explains the benefits and welfare implications of this practice. The chopping and placement of foods can alter desiccation rates, nutrient breakdown, and food contamination, so it is important to evaluate the implications of current practices. Here, the published literature on the behavioral impacts of different food presentation formats (such as clumped and scattered, and chopped and whole) is reviewed, with reference to a range of taxa. The current state of knowledge of the nutritional and microbiological effects of food presentation practices are also reviewed. Relevant research is available on the behavioral effects of some forms of zoo food presentation; however, relatively little research has been conducted on their nutrient composition effects or desiccation rates. Similarly, there are gaps in terms of the species that have been investigated, with a few mammalian taxa dominating the food presentation literature. Future research projects covering social, behavioral, and welfare impacts, and the nutritional and microbiological consequences of food presentation would further evidence-based zoo and aquarium management practices. Similarly, qualitative research surrounding keeper perception of food presentation formats would help to identify challenges and opportunities in this field.
  • 2.7K
  • 15 Oct 2020
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