Current protein & peptide science最新文献

Antimicrobial peptides (AMPs) are recognized for their potential application as new generation antibiotics, however, up to date, they have not been widely commercialized as expected. Although current bioinformatics tools can predict antimicrobial activity based on only amino acid sequences with astounding accuracy, peptide selectivity and potency are not foreseeable. This, in turn, creates a bottleneck not only in the discovery and isolation of promising candidates but, most importantly, in the design and development of novel synthetic peptides. In this paper, we discuss the challenges faced when trying to predict peptide selectivity and potency, based on peptide sequence, structure and relevant biophysical properties such as length, net charge and hydrophobicity. Here, pore-forming alpha-helical antimicrobial peptides family isolated from anurans was used as the case study. Our findings revealed no congruent relationship between the predicted peptide properties and reported microbial assay data, such as minimum inhibitory concentrations against microorganisms and hemolysis. In many instances, the peptides with the best physicochemical properties performed poorly against microbial strains. In some cases, the predicted properties were so similar that differences in activity amongst peptides of the same family could not be projected. Our general conclusion is that antimicrobial peptides of interest must be carefully examined since there is no universal strategy for accurately predicting their behavior.

Ferritin, as an iron storage protein, has the potential to inhibit ferroptosis by reducing excess intracellular free iron concentrations and lipid reactive oxygen species (ROS). An insufficient amount of ferritin is one of the conditions that can lead to ferroptosis through the Fenton reaction mediated by ferrous iron. Consequently, upregulation of ferritin at the transcriptional or posttranscriptional level may inhibit ferroptosis. In this review, we have discussed the essential role of ferritin in ferroptosis and the regulatory mechanism of ferroptosis in ferritin-deficient individuals. The description of the regulatory factors governing ferritin and its properties in regulating ferroptosis as underlying mechanisms for the pathologies of diseases will allow potential therapeutic approaches to be developed.

Introduction: Preeclampsia (PE) is an immensely prevalent condition that poses a significant risk to both maternal and fetal health. It is recognized as a primary cause of perinatal morbidity and mortality. Despite extensive research efforts, the precise impact of JDP2 on trophoblast invasion and migration in the context of preeclampsia remains unclear.

Materials and methods: The present study aimed to investigate the differential expression of JDP2 between normal control and preeclampsia placentas through the use of quantitative polymerase chain reaction (qPCR), western blotting, and immunostaining techniques. Furthermore, the effects of JDP2 overexpression and silencing on the migration, invasion, and wound healing capabilities of HTR-8/SVneo cells were evaluated. In addition, this study also examined the impact of JDP2 on epithelial-mesenchymal transition (EMT)-associated biomarkers and the Wnt/β-catenin pathway.

Results: In the present investigation, it was ascertained that Jun dimerization protein 2 (JDP2) exhibited a substantial decrease in expression levels in placentae afflicted with preeclampsia in comparison to those of normal placentae. Impairment in migration and invasion was noted upon JDP2 down-regulation, whereas augmentation of migration and invasion was observed upon JDP2 overexpression in HTR-8/SVneo cells. Subsequently, western blot and immunofluorescence assays were conducted, revealing marked alterations in EMT-associated biomarkers, such as E-cadherin, N-cadherin, and β-catenin, thereby indicating that JDP2 can facilitate cell invasion by modulating the EMT process in HTR-8/SVneo cells. Finally, activation of Wnt/β-catenin signaling was observed as a result of JDP2. After that, IWR-1, a Wnt inhibitor, was used in the recovery study. IWR-1 could inhibit the role of JDP2 in promoting migration and invasion in HTR-8/SVneo cells.

Conclusion: Our findings elucidated the impact of JDP2 on trophoblast invasion and migration in preeclampsia by suppressing the EMT through the Wnt/β-catenin signaling pathway, thereby offering a potential prognostic and therapeutic biomarker for this condition.

Introduction: Caleosins are recognized as the key proteins found in Lipid Droplets (LDs) and are crucial for the creation, maintenance, and breakdown of LDs. Nevertheless, our understanding of caleosins remains limited within Theaceae, a prominent botanical family encompassing economically significant tea and oil tea species.

Methods: In this research, we conducted a comprehensive genome-wide exploration and examination of the caleosin family in Theaceae species with sequenced genomes. The gene number of caleosin was similar among Theaceae species. Segmental duplication was the main form of caleosin expansion in Shuchazao (SCZ), Huangdan (HD), Biyun (BY), Tieguanyin (TGY), Longjing (LJ), C. lanceoleosa (Cla) and C. chekiangoleosa (CCH). Synteny analysis revealed one-to-more and more-to-one collinear relationships of caleosin genes among Theaceae species.

Results: Caleosins in Theaceae are categorized into either the H-family or the L-family, each exhibiting distinct motif structures and physicochemical properties. Expression analysis revealed an apparent flower-predominant expression pattern of caleosin genes in Theaceae species. In addition, most paralogous pairs displayed expression divergence.

Conclusion: This research enhanced our understanding of the lineage-specific evolution of caleosin genes in Theaceae, and is valuable for future functional analysis of this gene family in tea and oil-tea species.

Diet has emerged as a pivotal factor in the current time for diet-induced obesity (DIO). A diet overloaded with fats and carbohydrates and unhealthy dietary habits contribute to the development of DIO through several mechanisms. The prominent ones include the transition of normal gut microbiota to obese microbiota, under-expression of AMPK, and abnormally high levels of adipogenesis. DIO is the root of many diseases. The present review deals with various aspects of DIO and its target proteins that can be specifically used for its treatment. Also, the currently available treatment strategies have been explored. It was found that the expression of five proteins, namely, PPARγ, FTO, CDK4, 14-3-3 ζ protein, and Galectin-1, is upregulated in DIO. They can be used as potential targets for drug-designing studies. Thus, with these targets, the treatment strategy for DIO using natural bioactive compounds can be a safer alternative to medications and bariatric surgeries.

The diagnosis of intestinal injury remains a challenge as it is rare in occurrence and transpires in multiple traumatized patients. The deferred finding of injury of intestines upsurges multiple risks such as septicemia, numerous organ failures as well as mortality. In this review, we corroborate with the goals of proposing surrogate biomarkers that consent to the measurement of the permeability of intestines more effortlessly. The expression of intestinal fatty acid binding protein (I-FABP) is exclusive in the intestine and has beenreported to release extracellularly upon damage caused to tissues. This work focuses on evaluating the legitimacy of I-FABP as an initial biomarker to distinguish abdominal damage predominantly from an injury to the intestine.

Human paraoxonase 1 (hPON1) is a Ca2+-dependent metalloenzyme with multifunctional properties. Due to its diverse roles as arylesterase, phosphotriesterase, and lactonase, it plays a significant role in disease conditions. Researchers across the globe have demonstrated different properties of PON1, like anti-oxidant, anti-inflammatory, anti-atherogenic, anti-diabetic, and OPneutralization. Due to its pleotropic role in disease conditions like atherosclerosis, diabetes, cardiovascular diseases, neurodegenerative disorders, and OP-poisoning, it can be considered as a potential candidate for the development of therapeutic interventions. Attempts are being made in this direction to identify the exact role of PON1 in these disease conditions. Different approaches like directed evolution, genetic as well as chemical fusion, liposomal delivery of PON1, etc., are being developed and evaluated for their therapeutic effects in different pathological pathways. In this review, we outline the exact role and involvement of different properties of PON1 in the pathophysiology of different diseases and how it can be utilized and developed as a therapeutic intervention in PON1-associated disease conditions.

TLR4 stands at the forefront of innate immune responses, recognizing various pathogen- associated molecular patterns and endogenous ligands, thus serving as a pivotal mediator in the immune system's defense against infections and tissue damage. Beyond its canonical role in infection, emerging evidence highlights TLR4's involvement in numerous non-infectious human diseases, ranging from metabolic disorders to neurodegenerative conditions and cancer. Targeting TLR4 signaling pathways presents a promising therapeutic approach with broad applicability across these diverse pathological states. In metabolic disorders such as obesity and diabetes, dysregulated TLR4 activation contributes to chronic low-grade inflammation and insulin resistance, driving disease progression. In cardiovascular diseases, TLR4 signaling promotes vascular inflammation and atherogenesis, implicating its potential as a therapeutic target to mitigate cardiovascular risk. Neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, exhibit aberrant TLR4 activation linked to neuroinflammation and neuronal damage, suggesting TLR4 modulation as a strategy to attenuate neurodegeneration. Additionally, in cancer, TLR4 signaling within the tumor microenvironment promotes tumor progression, metastasis, and immune evasion, underscoring its relevance as a target for anticancer therapy. Advances in understanding TLR4 signaling cascades and their contributions to disease pathogenesis have spurred the development of various pharmacological agents targeting TLR4. These agents range from small molecule inhibitors to monoclonal antibodies, with some undergoing preclinical and clinical evaluations. Furthermore, strategies involving TLR4 modulation through dietary interventions and microbiota manipulation offer additional avenues for therapeutic exploration. Hence, targeting TLR4 holds significant promise as a therapeutic strategy across a spectrum of human diseases, offering the potential to modulate inflammation, restore immune homeostasis, and impede disease progression.

Alzheimer's disease (AD), the most common kind of dementia worldwide, is characterized by elevated levels of the amyloid-β (Aβ) peptide and hyperphosphorylated tau protein in the neurons. The complexity of AD makes the development of treatments infamously challenging. Apolipoprotein E (APOE) genes's ɛ4 allele is one of the main genetic risk factors for AD. While the APOE gene's ɛ4 allele considerably increases the chance of developing AD, the ɛ2 allele is protective compared to the prevalent ɛ3 variant. It is fiercely discussed how APOE affects the development and course of disease since it has a variety of activities that influence both neuronal and non-neuronal cells. ApoE4 contributes to the formation of tau tangles, deposition of Aβ, neuroinflammation, and other processes. Four decades of research have provided a significant understanding of the structure of APOE and how this may affect the neuropathology and pathogenesis of AD. APOE is a crucial lipid transporter essential for the growth of the central nervous system (CNS), upkeep, and repair. The mechanisms by which APOE contributes to the pathophysiology of AD are still up for discussion, though. Evidence suggests that APOE affects the brain's clearance and deposition of Aβ. Additionally, APOE has Aβ-independent pathways in AD, which has led to the identification of new functions for APOE, including mitochondrial dysfunction. This study summarizes important studies that describe how APOE4 affects well-known AD pathologies, including tau pathology, Aβ, neuroinflammation, and dysfunction of neural networks. This study also envisions some of the therapeutic approaches being used to target APOE4 in the hopes of preventing or treating AD.

Introduction: Clinic infections caused by various microorganisms are a public health concern. The rise of new strains resistant to traditional antibiotics has exacerbated the problem. Thus, the search for new antimicrobial molecules remains highly relevant.

Methods: The current study purified, characterized, and assessed the antimicrobial activity of a papain inhibitor from Terminalia catappa L. seeds.

Results: The inhibitor was purified by heating the crude extract at 80°C for 30 min, followed by ion exchange chromatography on a DEAE cellulose column. The purification index was 9-fold, yielding 2.3%. SDS-PAGE and size exclusion chromatography revealed that the protease inhibitor (TcPI) is a 15.9 kDa monomeric protein. The inhibition kinetics showed that TcPI is a competitive inhibitor specific to papain (Ki = 1.02 x 10-4 M). TcPI remained active even after heating at 100 ºC for 120 min and at pH conditions varying from 2.0 to 10.0. Even after 60 min, TcPI was resistant to papain proteolysis. TcPI exhibited antimicrobial activity against Candida parapsilosis and Staphylococcus aureus.

Conclusion: Here, we show that TcPI is a highly stable type-1 cystatin with the potential to combat infections caused by C. parapsilosis and S. aureus. Additional investigations into TcPI's structural aspects and mechanism of action, as well as safety assessments, are essential prerequisites for its potential application as a novel therapeutic intervention.