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These results show that the sericin protein might improve glycogen synthesis, accelerate glycolysis, and inhibit gluconeogenesis by enhancing the anti-oxidation capability and reducing inflammatory reactions. Therefore, sericin recovered by Ca(OH)2 degradation has potential use in the development of functional health foods that can lower blood sugar.Severe COVID-19 disease leads to hypoxemia, inflammation and lymphopenia. Viral infection induces cellular stress and causes the activation of the innate immune response. The ubiquitin-proteasome system (UPS) is highly implicated in viral immune response regulation. The main function of the proteasome is protein degradation in its active form, which recognises and binds to ubiquitylated proteins. Some proteasome subunits have been reported to be upregulated under hypoxic and hyperinflammatory conditions. Here, we conducted a prospective cohort study of COVID-19 patients (n = 44) and age-and sex-matched controls (n = 20). In this study, we suggested that hypoxia could induce the overexpression of certain genes encoding for subunits from the α and β core of the 20S proteasome and from regulatory particles (19S and 11S) in COVID-19 patients. Furthermore, the gene expression of proteasome subunits was associated with lymphocyte count reduction and positively correlated with inflammatory molecular and clinical markers. Given the importance of the proteasome in maintaining cellular homeostasis, including the regulation of the apoptotic and pyroptotic pathways, these results provide a potential link between COVID-19 complications and proteasome gene expression.Metalloproteins are involved in key cell processes such as photosynthesis, respiration, and oxygen transport. However, the presence of transition metals (notably iron as a component of [Fe-S] clusters) often makes these proteins sensitive to oxygen-induced degradation. Consequently, their study usually requires strict anaerobic conditions. Although X-ray crystallography has been the method of choice for solving macromolecular structures for many years, recently electron microscopy has also become an increasingly powerful structure-solving technique. We have used our previous experience with cryo-crystallography to develop a method to prepare cryo-EM grids in an anaerobic chamber and have applied it to solve the structures of apoferritin and the 3 [Fe4S4]-containing pyruvate ferredoxin oxidoreductase (PFOR) at 2.40 Å and 2.90 Å resolution, respectively. The maps are of similar quality to the ones obtained under air, thereby validating our method as an improvement in the structural investigation of oxygen-sensitive metalloproteins by cryo-EM.Recently, disease-associated variants of the TUBA4A gene were identified in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we present the neuropathological report of a patient with the semantic variant of primary progressive aphasia with a family history of Parkinsonism, harboring a novel frameshift mutation c.187del (p.Arg64Glyfs*90) in TUBA4A. Immunohistochemistry showed abundant TAR DNA-binding protein 43 kDa (TDP-43) dystrophic neurite pathology in the frontal and temporal cortex and the dentate gyrus of the hippocampus, consistent with frontotemporal lobar degeneration (FTLD). The observed pathology pattern fitted best with that of FTLD-TDP Type C. qPCR showed the presence of mutant TUBA4A mRNA. However, no truncated TUBA4A was detected at the protein level. A decrease in total TUBA4A mRNA and protein levels suggests loss-of-function as a potential pathogenic mechanism. This report strengthens the idea that N-terminal TUBA4A mutations are associated with FTLD-TDP. These N-terminal mutations possibly exert their pathogenic effects through haploinsufficiency, contrary to C-terminal TUBA4A mutations which are thought to disturb the microtubule network via a dominant-negative mechanism.Cell adhesion molecule L1 is a cell surface glycoprotein that promotes neuronal cell migration, fosters regeneration after spinal cord injury and ameliorates the consequences of neuronal degeneration in mouse and zebrafish models. Counter-indicative features of L1 were found in tumor progression the more L1 is expressed, the more tumor cells migrate and increase their metastatic potential. L1's metastatic potential is further evidenced by its promotion of epithelial-mesenchymal transition, endothelial cell transcytosis and resistance to chemo- and radiotherapy. These unfortunate features are indicated by observations that cells that normally do not express L1 are induced to express it when becoming malignant. With the aim to ameliorate the devastating functions of L1 in tumors, we designed an alternative approach to counteract tumor cell migration. Libraries of small organic compounds were screened using the ELISA competition approach similar to the one that we used for identifying L1 agonistic mimetics. Whereas in the former approach, a function-triggering monoclonal antibody was used for screening libraries, we here used the function-inhibiting monoclonal antibody 324 that reduces the migration of neurons. We now show that the L1 antagonistic mimetics anagrelide, 2-hydroxy-5-fluoropyrimidine and mestranol inhibit the migration of cultured tumor cells in an L1-dependent manner, raising hopes for therapy.The p53 family has the following three members p53, p63 and p73. p53 is a tumor suppressor gene that frequently exhibits mutation in head and neck cancer. Most p53 mutants are loss-of-function (LoF) mutants, but some acquire some oncogenic function, such as gain of function (GoF). It is known that the aggregation of mutant p53 can induce p53 GoF. The p73 activators RETRA and NSC59984 have an anti-cancer effect in p53 mutation cells, but we found that p73 activators were not effective in all head and neck squamous cell carcinoma (HNSCC) cell lines, with different p53 mutants. A comparison of the gene expression profiles of several regulator(s) in mutant HNSCC cells with or without aggregation of p53 revealed that nicotinamide phosphoribosyltransferase (NAMPT) is a key regulator of mutant p53 aggregation. An NAMPT inhibitor, to reduce abnormal aggregation of mutant p53, used in combination with a p73 activator, was able to effectively repress growth in HNSCC cells with p53 GoF mutants. This study, therefore, suggests a potential combination therapy approach for HNSCC with a p53 GoF mutation.Within this review, sex-specific differences in alveolar epithelial functions are discussed with special focus on preterm infants and the respiratory disorders associated with premature birth. First, a short overview about fetal lung development, the challenges the lung faces during perinatal lung transition to air breathing and respiratory distress in preterm infants is given. Next, clinical observations concerning sex-specific differences in pulmonary morbidity of human preterm infants are noted. The second part discusses potential sex-specific causes of pulmonary complications, including pulmonary steroid receptors and local lung steroid metabolism. With regard to pulmonary steroid metabolism, it is important to highlight which steroidogenic enzymes are expressed at which stage during fetal lung development. Thereafter, we review the knowledge concerning sex-specific aspects of lung growth and maturation. Special focus is given to alveolar epithelial Na+ transport as a driver of perinatal lung transition and the sex differences that were noted in this process.The distinct neuropathological features of the different α-Synucleinopathies, as well as the diversity of the α-Synuclein (α-Syn) intracellular inclusion bodies observed in post mortem brain sections, are thought to reflect the strain diversity characterizing invasive α-Syn amyloids. However, this "one strain, one disease" view is still hypothetical, and to date, a possible disease-specific contribution of non-amyloid factors has not been ruled out. In Multiple System Atrophy (MSA), the buildup of α-Syn inclusions in oligodendrocytes seems to result from the terminal storage of α-Syn amyloid aggregates first pre-assembled in neurons. This assembly occurs at the level of neuronal cytoplasmic inclusions, and even earlier, within neuronal intranuclear inclusions (NIIs). Intriguingly, α-Syn NIIs are never observed in α-Synucleinopathies other than MSA, suggesting that these inclusions originate (i) from the unique molecular properties of the α-Syn fibril strains encountered in this disease, or alternatively, (ii)injection of the fibril strain in mice. Our data thus show that the ability to seed NIIs is a strain property that is integrally encoded in the fibril supramolecular architecture. Upstream alterations of cellular mechanisms are not required. Cytoskeletal Signaling agonist In contrast to the lentiform TDP-43 NIIs, which are observed in certain frontotemporal dementias and which are conditional upon GRN or VCP mutations, our data support the hypothesis that the presence of α-Syn NIIs in MSA is instead purely amyloid-strain-dependent.Different approaches to develop engineered scaffolds for periodontal tissues regeneration have been proposed. In this review, innovations in stem cell technology and scaffolds engineering focused primarily on Periodontal Ligament (PDL) regeneration are discussed and analyzed based on results from pre-clinical in vivo studies and clinical trials. Most of those developments include the use of polymeric materials with different patterning and surface nanotopography and printing of complex and sophisticated multiphasic composite scaffolds with different compartments to accomodate for the different periodontal tissues' architecture. Despite the increased effort in producing these scaffolds and their undoubtable efficiency to guide and support tissue regeneration, appropriate source of cells is also needed to provide new tissue formation and various biological and mechanochemical cues from the Extraccellular Matrix (ECM) to provide biophysical stimuli for cell growth and differentiation. Cell sheet engineering is a novel promising technique that allows obtaining cells in a sheet format while preserving ECM components. The right combination of those factors has not been discovered yet and efforts are still needed to ameliorate regenerative outcomes towards the functional organisation of the developed tissues.Proinflammatory joint environment, coupled with impeded chondrogenic differentiation of mesenchymal stromal cells (MSCs), led to inferior cartilage repair outcomes. Nuclear translocation of phosphorylated-NFκB downregulates SOX9 and hinders the chondrogenesis of MSCs. Strategies that minimize the deleterious effects of NFκB, while promoting MSC chondrogenesis, are of interest. This study establishes the ability of continuous low-intensity ultrasound (cLIUS) to preserve MSC chondrogenesis in a proinflammatory environment. MSCs were seeded in alginatecollagen hydrogels and cultured for 21 days in an ultrasound-assisted bioreactor (5.0 MHz, 2.5 Vpp; 4 applications/day) in the presence of IL1β and evaluated by qRT-PCR and immunofluorescence. The differential expression of markers associated with the NFκB pathway was assessed upon a single exposure of cLIUS and assayed by Western blotting, qRT-PCR, and immunofluorescence. Mitochondrial potential was evaluated by tetramethylrhodamine methyl ester (TMRM) assay. The chondroinductive potential of cLIUS was noted by the increased expression of SOX9 and COLII.