Protein and Peptide Letters最新文献

Despite significant research efforts, Alzheimer's disease (AD), the primary cause of dementia in older adults worldwide, remains a neurological challenge for which there are currently no effective therapies. There are substantial financial, medical, and personal costs associated with this condition.Important pathological features of AD include hyperphosphorylated microtubule-associated protein Tau, the formation of amyloid β (Aβ) peptides from amyloid precursor protein (APP), and continuous inflammation that ultimately results in neuronal death. Important histological markers of AD, amyloid plaques, and neurofibrillary tangles are created when Aβ and hyperphosphorylated Tau build-up. Nevertheless, a thorough knowledge of the molecular players in AD pathophysiology is still elusive. Recent studies have shown how noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), regulate gene expression at the transcriptional and posttranscriptional levels in a variety of diseases, including AD. There is increasing evidence to support the involvement of these ncRNAs in the genesis and progression of AD, making them promising as biomarkers and therapeutic targets. As a result, therapeutic approaches that target regulatory ncRNAs are becoming more popular as potential means of preventing the progression of AD. This review explores the posttranscriptional relationships between ncRNAs and the main AD pathways, highlighting the potential of ncRNAs to advance AD treatment. In AD, ncRNAs, especially miRNAs, change expression and present potential targets for therapy. MiR-346 raises Aβ through APP messenger Ribonucleic Acid (mRNA), whereas miR-107 may decrease Aβ by targeting beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). They are promising early AD biomarkers due to their stability in cerebrospinal fluid (CSF) and blood. Furthermore, additional research is necessary to determine the role that RNA fragments present in AD-related protein deposits play in AD pathogenesis.

Background: There have been great efforts in vaccine design against HIV-1 since 1981. Various approaches have been investigated, including optimized delivery systems and effective adjuvants to enhance the efficacy of selective antigen targets. In this study, we evaluated the efficiency of IMT-P8 and LDP12 cell penetrating peptides in eliciting immune responses against HIV-1 Nef-MPER-V3 fusion protein as an antigen candidate. Moreover, the potency of HP91 and HSP27 was compared as an adjuvant in female BALB/c mice through different regimens.

Methods: For this purpose, the recombinant Nef-MPER-V3, IMT-P8-Nef-MPER-V3 and LDP-Nef- MPER-V3 proteins were generated on a large scale. After mice immunization with different regimens, the secretion of antibodies, cytokines and granzyme B was evaluated by ELISA.

Results: Our results demonstrated that immunized mice receiving the Nef-MPER-V3 linked to IMT-P8 exhibited significantly higher levels of IgG compared to other groups. The IMT-P8-Nef- MPER-V3 with the Hp91 group showed the highest level of humoral response, which was significantly stronger than the LDP12 formulation using the same antigen (LDP-Nef-MPER-V3). Additionally, the combination of IMT-P8-Nef-MPER-V3 with either Hp91 or Hsp27 resulted in robust induction of IFN-γ compared to the LDP-Nef-MPER-V3 group. Furthermore, cytotoxic T lymphocyte (CTL) activation and proliferation assays indicated that IMT-P8 served as a more effective CPP, particularly when used in conjunction with the Hp91 adjuvant.

Conclusion: Altogether, the data indicated that Nef-MPER-V3 antigen in different formulations was effective in eliciting immune responses. This fusion protein has the high potency to induce both immunity arms, specifically when incorporated with IMT-P8, which showed priority to LDP12. Moreover, HP91 resulted in a greater humoral and cellular immune activation compared to HSP27. These findings suggest the potential of IMT-P8 as a superior delivery system for enhancing immune responses in vaccine development.

Background: Aloperine (ALO) is an important active ingredient in the traditional Chinese medicinal plant Sophora alopecuroides L and has a significant autophagy-stimulating effect. The effect of ALO on cytotoxicity caused by UVB radiation in skin fibroblasts and the potential mechanism remains unclear.

Objective: The present study aimed to assess the effect of ALO on UVB-induced damage in skin fibroblasts and investigate its possible mechanism.

Methods: Cell viability, cytotoxicity, caspase-Glo 3/7 activity, apoptosis, and protein expression were measured in UVB-treated skin fibroblasts in the presence or absence of ALO. Autophagy inhibitors (chloroquine and bafilomycin A1) and TFE3 siRNA transfection were used to elucidate the potential mechanisms further.

Results: These data demonstrate that ALO attenuated cell viability inhibition, apoptosis, cytotoxicity, and alterations in autophagy-related proteins caused by UVB exposure in skin fibroblasts. ALO stimulates autophagy activation and TFE3 nuclear localization in UVB-treated skin fibroblasts. Furthermore, treatment with autophagy inhibitors and TFE3 siRNA reversed the effects of ALO on UVB-treated skin fibroblasts.

Conclusion: These results suggest that ALO protects skin fibroblasts against UVB-induced cytotoxicity by stimulating TFE3/Beclin-1-mediated autophagy.

Background: Colorectal cancer (CRC) is a prevalent form of cancer globally, characterized by a high mortality rate. Therefore, discovering effective therapeutic approaches for CRC treatment is critical.

Methods: The levels of KIF20A in CRC clinical samples were determined using Western Blot and immunofluorescence assay. SW480 cells were transfected with siRNA targeting KIF20A, while HT-29 cells were transfected with a KIF20A overexpression vector. Cell viability and apoptosis of CRC cells were assessed using CCK-8 and TUNEL analysis. Migration ability was investigated using Transwell. The levels of pyruvate, lactate and ATP were determined through corresponding assay kits. Western Blot was applied to confirm the level of proteins associated with glycolysis, c- Myc, HIF-1α, PKM2 and LDHA. Subsequently, functional rescue experiments were conducted to investigate further the regulatory relationship between KIF20A, c-Myc, and HIF-1α in colorectal cancer (CRC), employing the c-Myc inhibitor 10058-F4 and c-Myc overexpression plasmids.

Results: KIF20A was up-regulated in vivo and in vitro in CRC. KIF20A knockdown inhibited cell viability and migration while promoting cell apoptosis in SW480 cells. Conversely, overexpression of KIF20A yielded contrasting effects in HT-29 cells. Moreover, inhibition of KIF20A restrained the pyruvate, lactate production and ATP level, whereas overexpression of KIF20A enhanced the Warburg effect. Western Blot indicated that knockdown KIF20A attenuated the levels of c-Myc, HIF-1α, PKM2 and LDHA. In addition, rescue experiments further verified that KIF20A enhanced the Warburg effect by the KIF20A/c-Myc/HIF-1α axis in CRC.

Conclusion: KIF20A, being a crucial regulator in the progression of CRC, has the potential to be a promising therapeutic target for the treatment of CRC.

Background: The Disintegrin and Metalloproteinase (ADAM) family, also known as the metalloproteinase/disintegrin/cysteine-rich (MDC) proteins, includes both secreted and transmembrane molecules involved in critical biological processes, such as cell migration, adhesion, and signaling. This study aimed to investigate the evolutionary relationships and structural characteristics of disintegrin and metalloproteinase proteins identified in the venom gland transcriptome of the scorpion Hemiscorpius lepturus.

Methods: Using bioinformatics tools, we analyzed the open reading frame, conserved motifs, and primary, secondary, and tertiary structures of these proteins. Five proteins, named HLDisMet1, HLDisMet2, HLDisMet3, HLDisMet4, and HLDisMet5, were identified. Their predicted 3-D structures were within normal ranges (Z-score between -4 to -9).

Results: Phylogenetic analysis revealed that HLDisMet1 shares similarities with proteins from various spider species (Nephila pilipes, Argiope bruennichi, Araneus ventricosus, and Trichonephila inaurata madagascariensis), HLDisMet2 with the scorpion Centruroides sculpturatus, HLDis- Met4 with the scorpion Tityus serrulatus, and HLDisMet5 with several snake species (Python bivittatus, Vipera anatolica senliki, Protobothrops mucrosquamatus, and Naja naja).

Conclusion: These findings highlight the significant similarities between HLDisMet proteins and those found in other venomous species, suggesting a complex and diverse evolutionary pathway for venom components. The cross-species conservation observed may indicate a convergent evolutionary strategy, where different species independently develop similar venom components to adapt to similar ecological niches or prey types. This study highlights the evolutionary significance of venom diversification and its potential applications in understanding venom biology across different species.

An error was found in the affiliations of the author in the article titled 'Investigation of the Expression and Regulation of SCG5 in the Context of the Chromogranin-Secretogranin Family in Malignant Tumors'', published in Protein and Peptide Letters, 2024, 31(9), 657-666 [1]. Details of the error and a correction are provided here. Original: *Address correspondence to these authors at the Department of Thoracic Surgery, The Sixth Affiliated Hospital of Nantong University, Yancheng Third People's Hospital, Yancheng 224000, P.R. China; E-mail: jxsongycsy@163.com (J.S.) Corrected: *Address correspondence to these authors at the Department of Thoracic Surgery, The Sixth Affiliated Hospital of Nantong University, Yancheng Third People's Hospital, Yancheng 224000, P.R. China; E-mail: jxsongycsy@163.com (J.S.); Department of General Medicine, The Sixth Affiliated Hospital of Nantong University, Yancheng Third People's Hospital, Yancheng 224000, P.R. China; E-mail: ycsy161317@163.com (X.L.). We regret the error and apologize to readers. The original article can be found online at: http://dx.doi.org/10.2174/0109298665325956240819064853 PMID: 39219421.

The SCG5 gene has been demonstrated to play an essential role in the development and progression of a range of malignant neoplasms. The regulation of SCG5 expression involves multiple biological pathways. According to relevant studies, SCG5 is differentially expressed in different cancers, and its up- or down-regulation may even affect tumour growth, invasion, and migration, which caught our attention. Therefore, we summarise the regulatory roles played by the SCG5 gene in a variety of cancers and the biological regulatory mechanisms associated with its possible promotion or inhibition of tumour biological behavior, to further explore the potential of SCG5 as a new tumour marker and hopefully provide theoretical guidance for subsequent disease research and treatment.

Objectives: In this study, we employed an in vitro culturing technique to investigate the impact of p53 on the modulation of growth-associated protein-43 (GAP-43) within the primary cortical neurons of rat specimens.

Methods: (1) Within the first 24 hours after birth, the bilateral cortex was extracted from newborn Wistar rats and primary cortical neurons were cultured and identified. (2) The changes in the mRNA and protein expressions of GAP-43 induced by p53 in rat primary cortical neurons cultured in vitro were identified utilizing real-time polymerase chain reaction and western blot techniques.

Results: (1) Lentiviral transfection of p53 within primary cortical neurons of rats elicited elevated levels of both mRNA and protein expressions of GAP-43, consequently culminating in a noteworthy augmentation of p53 expression. (2) The introduction of a p53 inhibitor in rat primary cortical neurons resulted in a reduction in both mRNA and protein expressions of GAP-43.

Conclusion: Within primary rat cortical neurons, p53 has the potential to prompt an augmentation in both the transcriptional and protein expression levels of the GAP-43 protein.

Background: Staphylococcus aureus is a common pathogen with strains that are resistant to existing antibiotics. MurJ from S. aureus (SaMurJ), an integral membrane protein functioning as Lipid II flippase, is a potential target for developing new antibacterial agents against this pathogen. Successful expression and purification of this protein shall be useful in the development of drugs against this target.

Objective: In this study, we demonstrated the optimized expression and purification procedures of SaMurJ, identified suitable detergent for extracting and solubilizing the protein, and examined the peptidisc system to generate a detergent-free environment.

Methods: SaMurJ fused with N-terminal ten-His tag was expressed without induction. Six detergents were selected for screening the most efficient candidate for extraction and solubilization of the protein. The thermostability of the detergent-solubilized protein was assessed by evaluated temperature incubation. Different ratios of peptidisc bi-helical peptide (NSPr) to SaMurJ were mixed and the on-bead peptidisc assembly method was applied.

Results: SaMurJ expressed in BL21(DE3) was confirmed by peptide fingerprinting, with a yield of 1 mg SaMurJ per liter culture. DDM was identified as the optimum detergent for solubilization and the nickel affinity column enabled SaMurJ purification with a purity of ~88%. However, NSPr could not stabilize SaMurJ.

Conclusion: The expression and purification of SaMurJ were successful, with high purity and good yield. SaMurJ can be solubilized and stabilized by a DDM-containing buffer.

Malaria caused by Plasmodium falciparum (Pf) is an illness that contributes significantly to the global health burden. Pf makes significant alterations to the host cell to meet its metabolic demands and escape the immune response of the host. These include the export of a large number of parasite proteins to the infected Red Blood Cells (iRBC). Variable Surface Antigens (VSAs), which are highly polymorphic protein families with important roles in immune evasion, form an important component of the exported proteins. A total of five protein families constitute the VSAs, viz. PfEMP1 (Pf erythrocyte membrane protein 1), RIFIN (repetitive interspersed family), STEVOR (sub-telomeric open reading frame), SURFIN (surface-associated interspersed gene family), and PfMC-2TM (Pf Maurer's cleft two transmembrane). With orthologues present in various simian-infecting species, VSAs take up a variety of domain topologies and organizational structures while exhibiting differential expressions throughout the parasite life cycle. Their expression varies across clinical isolates and laboratory strains, which suggests their crucial role in host cell survival and defense. Members of VSAs are reported to contribute significantly to disease pathogenesis through immune evasion processes like cytoadherence, iRBC sequestration in the host vasculature, rosetting, reduced erythrocyte deformability, and direct immunosuppression. In this study, we have gathered information on various aspects of VSAs, like their orthologues, domain architecture, surface topology, functions and interactions, and three-dimensional structures, while emphasizing discoveries in the field. Considering the vast repertoire of Plasmodial VSAs with new emergent functions, a lot remains unknown about these families and, hence, malaria biology.