Current protein & peptide science最新文献

ASXL2, as a transcription regulator, is a research hotspot for tumor detection. The aberrant expression of ASXL2 protein has been mainly implicated in malignant hematological and heart diseases. To further explore the predictive value of ASXL2 in diseases, we reviewed the structure and function of ASXL2 protein, the post-translational modification mechanism, and the expression of ASXL2 protein in the pathogenesis of different diseases to provide a theoretical basis and support for the development of future treatments.

Typically, materials used to create optical devices have chemical and physical properties that have been precisely designed for a narrowly defined purpose, allowing for changes in design to account for device variability. There is a growing need for devices built of materials with changeable optical responses, as optical systems are incorporated into platforms with much functionality. Regenerated silk fibroin is described in this article as an enabling gadget with an active optical response as a result of the inherent characteristics of proteins. Silk's capacity for controlled movement, to swell and shrink reversibly, alter conformation and degradation that is customizable, impacts both the shape and the response of the optical structure-representative silk-based gadgets. The diversity of silk material is shown and discussed in this paper, concentrating on architectures that show reconfigurable behavior, an optical waveguide that is physically temporary and provides reversible responses. Finally, innovative research directions for silk-based materials and optical devices are presented in this paper. Since ancient times, silk, a natural biopolymer, has been used as a repair material in medicine. In the past 20 years, it has attracted a lot of interest to be used in several biomedical applications. Various healthcare items with silk as their substrate have been developed thanks to significant advancements in silk biomaterial research. Silk is a fabric created from spider and silkworm cocoons. Hierarchical structures and conventional structural elements are present in them. Different silk types can be produced using certain methods, such as films, fibers, microspheres, sponges, and hydrogels. The structural characteristics of secondary proteins present in silk can also be modified. This paper investigates the use of silk in biomedical and optical applications, and examines the technical trend in electronic fields.

Platelets and their progenitors express high levels of integrin αIIbβ3, which plays a key role in platelet functions, hemostasis, and arterial thrombosis. Because of their quick and high efficacy, the three anti-αIIbβ3 drugs, abciximab, eptifibatide, and tirofiban, are regarded as potent anti-thrombotics and clinically approved by US Food and Drug Administration. However, because they interfere with the inside-out signaling of αIIbβ3, which is required for stable platelet adhesion and aggregation, the application of abciximab, eptifibatide, and tirofiban is restricted to patients undergoing percutaneous coronary intervention. On the other hand, the outside-in signaling of αIIbβ3 in platelets appears to be responsible for thrombus stabilization, and selective interference with the propagation of outside-in signals might signify a new therapeutic strategy to preferentially inhibit platelet-rich arterial thrombosis with less bleeding issues caused by way of compromised major hemostasis. The purpose of this review is to describe the bidirectional signal transduction of integrin αIIbβ3 in platelets with a focus on outside-in signaling, more efficient and safer anti-αIIbβ3 peptides, and the potential drug targets for future anti-platelet research.

Background: Osteoporosis is a systemic bone disease with low bone mass, destruction of bone microstructure, and increased bone fragility. Gender and metabolic status are well-known risk factors for osteoporosis. Irisin is a newly discovered myokine that is secreted by skeletal muscle and adipose tissue. Serum Irisin was reported to be decreased in type 2 diabetes mellitus (T2DM) and/or osteoporosis patients, and it is correlated with bone mineral density (BMD) of neck bone, but its role in postmenopausal T2DM with osteoporosis remains largely unknown.

Methods: Postmenopausal T2DM patients with or without osteoporosis were recruited, and 50 agematched healthy postmenopausal women were employed as healthy control. C57BL/6J mice were intraperitoneally injected with 65 mg/kg Streptozotocin (STZ) daily for consecutive 5 days to induce diabetes, and 1 mg/kg recombinant Irisin protein was injected into diabetic mice through the tail vein once a week for 4 months.

Results: Compared to that of healthy control, serum Irisin levels and BMD in L1-L4 lumbar spine, femoral neck, total hip, and Wards were decreased in postmenopausal T2DM patients and further decreased in T2DM patients with osteoporosis. Moreover, serum Irisin levels were also correlated with BMD in the above body parts in T2DM patients. Furthermore, recombinant Irisin protein improved diabetic osteoporosis and inflammation in STZ-induced diabetic mice with osteoporosis.

Conclusion: Serum Irisin levels in postmenopausal T2DM patients with osteoporosis were significantly decreased, which may be related to the decreased BMD and the occurrence of osteoporosis in postmenopausal T2DM patients. The combined measurement of serum Irisin levels and BMD in patients with T2DM in the early stage has a certain effect on the diagnosis and treatment of osteoporosis.

Hypoxia, a prevalent characteristic of both solid and liquid malignancies, is found to regulate how genes are expressed in a way that promotes cellular adaptability and survival. Metastasis is controlled by hypoxia-inducible factors (HIFs). HIFs are dimeric protein molecules made up of an oxygen (O₂) responsive HIF-1α, HIF-2α, or HIF-3α domain and a periodically produced HIF-1β portion (also known as ARNT). Nevertheless, it is important to note that HIFs degrade under normoxic conditions. A large multitude of different biological operations, including vessels generation, oxygen delivery, stemness, pluripotency, multiplication, epithelial to mesenchymal shift, metastatic prevalence and intrusion, redox equilibrium, and programmed cell death, are strictly controlled by over 70 immediate HIF target genes that have been reported. Metabolic reprogramming, which modulates cellular energy generation aside from oxidative phosphorylation and concerning glycolysis, is among the core tasks of HIF target genes. As a result, choosing HIFs as a primary target in the treatment of various tumors is essential. We have a very limited understanding of this extremely complex topic, which is characterised by hypoxia- induced resistance. In order to combat this, scientists are investigating numerous cutting-edge approaches. Traditional chemotherapeutic drugs used to treat cancer are frequently linked to unfavourable side effects and the development of chemoresistance. The use of natural compounds in conjunction with chemotherapy drugs is rising as a result of their capacity to alter a number of molecular practices with a lower detrimental impact. Experimental and clinical research is accumulating evidence that phytochemicals can influence the genesis and progression of cancer by favourably modulating a number of signalling pathways. Combinations of phytochemicals are potent cancer treatment options because they incentivise apoptosis, limit cell prevalence, make cancerous cells more susceptible, and escalate immunity. Despite being characterised, HIF-1-independent mechanisms for medication resistance in hypoxia are still infrequently reported. The prime aim of the article is to summarise the most recent research on the molecular basis of hypoxia-induced chemoresistance and how chemotherapy and phytochemicals can be used to treat cancer patients who are resistant to drugs.

Background: A hallmark pathology of Alzheimer's disease (AD) is the construction of neurofibrillary tangles, which are made of hyperphosphorylated Tau. The cis-proline isomer of the pThr/Ser-Pro sequence has been suggested to act as an aggregation precursor according to the 'Cistauosis' hypothesis; however, this aggregation scheme is not yet completely approved. Various peptidyl-prolyl isomerases (PPIases) may specifically isomerize cis/trans-proline bonds and restitute Tau's ability to attach microtubules and may control Tau amyloid aggregation in AD.

Methods: In this study, we provided experimental evidence for indicating the effects of the plant Cyclophilin (P-Cyp) from Platanus orientalis pollens on the Tau aggregation by various spectroscopic techniques.

Results: Our findings disclosed that the rate/extent of amyloid formation in the Tau sample which is incubated with P-Cyp decreased and these observations do not seem to be due to the macromolecular crowding effect. Also, as proven that 80% of the prolines in the unfolded protein are in the trans conformation, urea-induced unfolding analyses confirmed this conclusion and showed that the aggregation rate/extent of urea-treated Tau samples decreased compared with those of the native protein. Also, XRD analysis indicated the reduction of scattering intensities and beta structures of amyloid fibrils in the presence of P-Cyp. Therefore, the ability of P-Cyp to suppress Tau aggregation probably depends on cis to trans isomerization of proline peptide bonds (X-Pro) and decreasing cis isomers in vitro.

Conclusion: The findings of the current study may inspire possible protective/detrimental effects of various types of cyclophilins on AD onset/progression through direct regulation of intracellular Tau molecules and provides evidence that a protein from a plant source is able to enter the cell cytoplasm and may affect the behavior of cytoplasmic proteins.

Aims: To reveal the prognostic role of unfolded protein response (UPR) -related genes in hepatocellular carcinoma (HCC).

Background: Hepatocellular carcinoma is a genetically heterogeneous tumor, and the prediction of its prognosis remains a challenge. Studies elucidating the molecular mechanisms of UPR have rapidly increased. However, the UPR molecular subtype characteristics of the related genes in HCC progression have yet to be thoroughly studied.

Objective: Conducting a comprehensive assessment of the prognostic signature of genes related to the UPR in patients with HCC can advance our understanding of the cellular processes contributing to the progression of HCC and offer innovative strategies in precise therapy.

Methods: Based on the gene expression profiles associated with UPR in HCC, we explored the molecular subtypes mediated by UPR-related genes and constructed a UPR-related genes signature that could precisely predict the prognosis for HCC.

Results: Using microarray data of HCC patients, differentially expressed UPR-related genes (DEGs) were discovered in malignancies and normal tissues. The HCC was classified into two molecular subtypes by the NMF algorithm based on DEGs modification of the UPR. Moreover, we developed a UPR-related model for predicting HCC patients' prognosis. The robustness of the UPR- related model was confirmed in external validation. Moreover, we analyzed immune responses in different risk groups. Analysis of immune functions revealed that Treg, Macrophages, aDCs, and MHC class-I were significantly up-regulated in high-risk HCC. At the same time, cytolytic activity and type I and II INF response were higher in a low-risk subgroup.

Conclusion: This study identified two UPR molecular subtypes of HCC and developed a ten-gene HCC prognostic signature model (EXTL3, PPP2R5B, ZBTB17, CCT3, CCT4, CCT5, GRPEL2, HSP90AA1, PDRG1, and STC2), which can robustly forecast the progression of HCC.

Background: Multidrug-resistant (MDR) methicillin-resistant Staphylococcus aureus (MRSA) has become a prime health concern globally. These bacteria are found in hospital areas where they are regularly dealing with antibiotics. This brings many possibilities for its mutation, so drug resistance occurs.

Introduction: Nowadays, these nosocomial MRSA strains spread into the community and live stocks. Resistance in Staphylococcus aureus is due to mutations in their genetic elements.

Methods: As the bacteria become resistant to antibiotics, new approaches like antimicrobial peptides (AMPs) play a vital role and are more efficacious, economical, time, and energy saviours.

Results: Machine learning approaches of Artificial Intelligence are the in silico technique which has their importance in better prediction, analysis, and fetching of important details regarding AMPs.

Conclusion: Anti-microbial peptides could be the next-generation solution to combat drug resistance among Superbugs. For better prediction and analysis, implementing the in silico technique is beneficial for fast and more accurate results.

Introduction: The proteins of the Bin/Amphiphysin/Rvs167 (BAR) domain superfamily are believed to induce membrane curvature. PICK1 is a distinctive protein that consists of both a BAR and a PDZ domain, and it has been associated with numerous diseases. It is known to facilitate membrane curvature during receptor-mediated endocytosis. In addition to understanding how the BAR domain facilitates membrane curvature, it's particularly interesting to unravel the hidden links between the structural and mechanical properties of the PICK1 BAR domain.

Methods: This paper employs steered molecular dynamics (SMD) to investigate the mechanical properties associated with structural changes in the PICK1 BAR domains.

Results: Our findings suggest that not only do helix kinks assist in generating curvature of BAR domains, but they may also provide the additional flexibility required to initiate the binding between BAR domains and the membrane.

Conclusion: We have observed a complex interaction network within the BAR monomer and at the binding interface of the two BAR monomers. This network is crucial for maintaining the mechanical properties of the BAR dimer. Owing to this interaction network, the PICK1 BAR dimer exhibits different responses to external forces applied in opposite directions.

Cancer diseases account for about 15% of deaths globally right now, and the percentage may increase in the future. There are more than 100 types of cancer, and each of them is distinct in its origin, microenvironment, growth, metastasis, and signalling pathways. Cancer stem cells are the specialised cells that make cancer more aggressive and difficult to treat. Moreover, cancer aetiology may exist at the genomic, proteomic, or habitat level in any combination. Hence, a unanimous treatment protocol for the different cancers is an uphill task at the present juncture. In this context, this review aims to provide a comprehensive reappraisal concisely of anti-apoptotic proteins, which are shown to be overexpressed in most cancers, if not all, and to forthrightly rationalise the apoptotic proteins as potential biomarkers and druggable targets of the cancers by effectively killing cancer stem cells.