Holgersenmorris9484

Intermediate filaments (IFs) perform a diverse set of well-known functions including providing structural support for the cell and resistance to mechanical stress, yet recent evidence has revealed unexpected roles for IFs as stress response proteins. Previously, it was shown that the type III IF protein vimentin forms cage-like structures around centrosome-associated proteins destined for degradation, structures referred to as aggresomes, suggesting a role for vimentin in protein turnover. However, vimentin's function at the aggresome has remained largely understudied. In a recent report, vimentin was shown to be dispensable for aggresome formation, but played a critical role in protein turnover at the aggresome through localizing proteostasis-related machineries, such as proteasomes, to the aggresome. Here, we review evidence for vimentin's function in proteostasis and highlight the organismal implications of these findings.Cyanophyta-phycocyanin (C-PC) is the main constituent of the rod of phycobilisome (PBS), which is a highly ordered and large peripheral light-harvesting protein complex present on the cytoplasmic side of the thylakoid membrane in cyanobacteria and red algae. The C-PC monomer comprises two chains, α- and β-subunits, and aggregates to form ring-shaped trimers (αβ)3 with rotational symmetry. The ring-shaped trimer (αβ)3 is a structural block unit (SBU) that forms the rod of PBS. Two (αβ)3 SBUs are arranged in a face-to-face manner to form an (αβ)6 -hexamer. In this study, the electronic states of three phycocyanobilins, α84, β84, and β155 in C-phycocyanin, constituting the rod of the PBS, were calculated for both the trimer and hexamer models by considering the effect of the electrostatic field of protein moieties and water molecules. For the hexamer, the absorption wavelengths of α84, β84, and β155 were similar to those obtained experimentally; however, for the trimer, only the absorption wavelength of β155 shifted toward a shorter-wavelength. The nature of the hexamer structure as a hierarchical structure is revealed by considering the calculated absorption wavelength and energy transfer.Over the years, developments in oncology led to significantly improved clinical outcome for cancer patients. However, cancer recurrence after initial treatment response still poses a major challenge, as it often involves more aggressive, metastatic disease. The presence of dormant cancer cells is associated with recurrence, metastasis, and poor clinical outcome, suggesting that these cells may play a crucial role in the process of disease relapse. Cancer cell dormancy typically presents as growth arrest while retaining proliferative capacity and can be induced or reversed by a wide array of cell-intrinsic and cell-extrinsic factors. Conventional therapies preferentially target fast-dividing cells, leaving dormant cancer cells largely insensitive to these treatments. In this review, we discuss the role of dormant cancer cells in cancer recurrence and highlight how novel therapy strategies based on cell-cycle modulation, modifications of existing drugs, or enhanced drug-delivery vehicles may be used to specifically target this subpopulation of tumor cells, and thereby have the potential to prevent disease recurrence.The severity of coronavirus disease 2019 (COVID-19) is a crucial problem in patient treatment and outcome. HADA chemical manufacturer The aim of this study is to evaluate circulating level of sphingosine-1-phosphate (S1P) along with severity markers, in COVID-19 patients. One hundred eleven COVID-19 patients and forty-seven healthy subjects were included. The severity of COVID-19 was found significantly associated with anemia, lymphocytopenia, and significant increase of neutrophil-to-lymphocyte ratio, ferritin, fibrinogen, aminotransferases, lactate dehydrogenase (LDH), C-reactive protein (CRP), and D-dimer. Serum S1P level was inversely associated with COVID-19 severity, being significantly correlated with CRP, LDH, ferritin, and D-dimer. The decrease in S1P was strongly associated with the number of erythrocytes, the major source of plasma S1P, and both apolipoprotein M and albumin, the major transporters of blood S1P. Not last, S1P was found to be a relevant predictor of admission to an intensive care unit, and patient's outcome. Circulating S1P emerged as negative biomarker of severity/mortality of COVID-19 patients. Restoring abnormal S1P levels to a normal range may have the potential to be a therapeutic target in patients with COVID-19.Osteonecrosis of the femoral head (ONFH) is a common clinical disease with a high disability rate. Apoptosis of osteoblasts caused by high-dose short-term or low-dose long-term glucocorticoid (GC) administration is the biological basis of steroid-induced avascular necrosis of the femoral head (SANFH). The pathogenesis of SANFH has not yet been fully elucidated, and there is currently a lack of effective clinical treatments. Here, we investigated the role of the reactive oxygen species (ROS)/JNK/c-Jun signaling pathway in SANFH. Dexamethasone (Dex) was used to induce apoptosis in osteoblasts, and this resulted in a significant increase in levels of p-JNK, p-c-Jun, Bax, caspase-3, caspase-9, cytochrome C, Beclin-1, and LC3, and a decrease in levels of P62 and Bcl-2. In addition, intracellular ROS levels were increased and mitochondrial membrane potential was decreased. Administration of 3-MA, an autophagy inhibitor, attenuated Dex-mediated changes in autophagy and apoptosis. A rat model of ONFH exhibited severe bone trabecular hollow bone pits along with a significant increase in femoral head cell apoptosis compared with the control group. Additionally, micro-CT analysis showed that both bone tissue content and femoral head integrity were significantly reduced in the ONFH group. Furthermore, 3-MA treatment decreased the effect of Dex on GC-induced ONFH and osteoblast apoptosis in rats and could counteract microstructure destruction due to femoral head necrosis. In summary, our data suggest that GC can induce osteoblast apoptosis and autophagy through the ROS/JNK/c-Jun signaling pathway, which contributes to ONFH.