Current protein & peptide science最新文献

Objectives: The aim of this study was to investigate the expression characteristics and interrelationships of FNDC5 and pyroptosis-associated molecules in peripheral blood mononuclear cells of patients with coronary heart disease (CHD).

Methods: Patients were divided into stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI) groups based on different clinical symptoms. According to the Gensini score, they were then divided into mild, moderate, and severe lesion groups. The control (NC) group was also set. ELISA assay was employed to detect the levels of Irisin, IL-1β, and IL-18, and the levels of pyroptosis-associated molecules, NF-κB p50, NF-κB p65, and FNDC5 were detected and compared by qRT-PCR and Western blot (WB). Logistic regression and Spearman's partial correlation analysis were used to analyze the pathogenic factors of CHD and explore the interrelationships between FNDC5 and the molecules.

Results: IL-1β and IL-18 of CHD patients were increased, while the Irisin was decreased. With the aggravation of symptoms and severity of coronary artery stenosis, the former increased, and the Irisin gradually decreased (P<0.05). About qRT-PCR and WB: With the aggravation of symptoms, the levels of pyroptosis-associated molecules and other indicators were increased, and FNDC5 was decreased (Pπ0.05). NLRP3, Caspase-1, and NF-κB p50 protein were positively correlated with the incidence of CHD, and FNDC5 was also negatively correlated with that of CHD. Even when common risk factors for CHD were taken into account, FNDC5 and NLRP3 were still found to be negatively connected.

Conclusion: The decreased expression level of FNDC5 and the increased level of pyroptosis-associated molecules may be related to CHD.

The three-dimensional structure of proteins, achieved through the folding of the nascent polypeptide chain in vivo, is largely facilitated by molecular chaperones, which are crucial for determining protein functionality. In addition to aiding in the folding process, chaperones target misfolded proteins for degradation, acting as a quality control system within the cell. Defective protein folding has been implicated in a wide range of clinical conditions, including neurodegenerative and metabolic disorders. It is now well understood that the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and Creutzfeldt-Jakob disease shares a common mechanism: the accumulation of misfolded proteins, which aggregate and become toxic to cells. Among the family of molecular chaperones, Heat Shock Proteins (HSPs) are highly expressed in response to cellular stress and play a pivotal role in preventing protein aggregation. Specific chaperones, particularly HSPs, are now recognized as critical in halting the accumulation and aggregation of misfolded proteins in these conditions. Consequently, these chaperones are increasingly considered promising pharmacological targets for the treatment of protein aggregation-related diseases. This review highlights research exploring the potential roles of specific molecular chaperones in disorders characterized by the accumulation of misfolded proteins.

Introduction: Membraneless organelles, such as nucleoli, stress granules, and P-bodies, are not enclosed by lipid membranes; rather, they are formed through a process known as liquid-liquid phase separation. To fully understand the biophysics behind the formation and regulation of these organelles, knowledge that has significant implications for cellular biology and disease research, the creation of phase diagrams is essential. Phase diagrams help clarify the physical and chemical conditions under which these organelles form, exist, and function within cells. However, methods for creating phase diagrams are often limited when the equation of state is unknown, a challenge that becomes more pronounced with increasing system complexity. While several methods exist to address this issue, their application is not universal.

Methods: We present a new method based on the SPACEBALL algorithm and cluster size monitoring, which enables the determination of binodal and spinodal line positions by analyzing system clustering during molecular dynamics simulations of a well-studied van der Waals fluid under various conditions.

Results: Based on an analysis of the system's clustering behavior, we constructed the phase diagram for the monoatomic van der Waals fluid simulated at various densities and temperatures, observing that uniformly distributed van der Waals beads aggregate, causing changes in the system's density.

Discussion: Using the generated data, we discuss how a fitting function can be used to determine the binodal line location, and how observations of the system's density fluctuations can be used to determine the spinodal line location and assess the critical temperature.

Conclusion: We have presented alternative methods for locating phase boundaries in protein solutions, where the absence of a validated equation of state necessitates innovative approaches and makes traditional methods challenging to apply. Our SPACEBALL-based approach enables the creation of phase diagrams using pure trajectories obtained from molecular dynamics simulations.

One of the most well-known instances of an interdisciplinary subject is tissue engineering, where experts from many backgrounds collaborate to address important health issues and improve people's quality of life. Many researchers are interested in using chitosan and its derivatives as an alternative to fabricating scaffold engineering and skin grafts in tissue because of its natural abundance, affordability, biodegradability, biocompatibility, and wound healing properties. Nanomaterials based on peptides can provide cells with the essential biological cues required to promote cellular adhesion and are easily fabricated. Due to such worthy properties of chitosan and peptide, they find their application in tissue engineering and regeneration processes. The implementation of hybrids of chitosan and peptide is increasing in the field of tissue engineering and scaffolding for improved cellular adherence and bioactivity. This review covers the individual applications of peptide and chitosan in tissue engineering and further discusses the role of their conjugates in the same. Here, the recent findings are also discussed, along with studies involving the use of these hybrids in tissue engineering applications.

Human paraoxonase 1 (hPON1) is a Ca2+-dependent metalloenzyme with multifunctional properties. Due to its diverse activities (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 conditions. 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.

Introduction/objectives: Silver nanoparticles (AgNPs) are promising antimicrobial agents, but their synthesis often involves toxic reducing agents. To address this, we developed a green synthesis methodology employing an in-situ approach for synthesizing AgNPs within self- -assembled ultrashort peptide hydrogels through photochemical synthesis, eliminating the need for toxic chemicals.

Methods: A novel tetrapeptide was designed and synthesized to form hydrogels in aqueous solutions. AgNPs were incorporated into the hydrogel via in-situ photochemical synthesis using sunlight. The hydrogel and AgNPs were characterized through spectroscopic and microscopic techniques. The antibacterial efficacy of the AgNP-loaded hydrogel was assessed against gram-positive and gram-negative bacteria, and its wound-healing potential in mammalian cell lines was evaluated.

Results: Among the peptides synthesized, PHG-2 formed a hydrogel at a 1% w/v concentration in aqueous solution. Characterization using the gel inversion assay, circular dichroism (CD) spectroscopy, and transmission electron microscopy (TEM) revealed uniform nanofibril self-assembly. UV spectroscopy and TEM confirmed the formation of AgNPs within the hydrogel. While the peptide hydrogel exhibited moderate antibacterial activity alone, the AgNP-loaded hydrogel demonstrated synergistic antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. A docking study of all the synthesized peptides was performed against FmtA (an enzyme for cell wall synthesis of MRSA) and results were correlated with the obtained docking score. The silver-loaded peptide hydrogel showed a twofold increase in antibacterial activity against MRSA compared to silver nitrate solutions. The hydrogel significantly promoted wound healing in HEK-293T and MCF-7 cells compared to the control.

Conclusions: This study introduces a novel ultrashort tetrapeptide sequence for developing antibacterial agents that are effective against infected wounds while supporting wound healing. Utilizing in-situ photochemical synthesis, the green synthesis approach provides an environmentally friendly and sustainable alternative to conventional methods.

Background: Hypogalactia and agalactia in lactating mothers are the major causes of child malnutrition, mortality, morbidity, and overall ill health. The development of such treatments requires a well-designed preclinical study with suitable laboratory animals, which needs to be improved. Thus, a suitably designed study with a laboratory animal to analyse galactagogue activity, along with an assessment of the quality and quantity of milk, is required.

Objectives: This study aimed to evaluate the potential of rabbit as an animal model for studying lactogenic activity.

Methods: The structural homology of prolactin, gene prolactin receptor, and prolactin hormone in humans, rabbit, and rat was studied using BLAST and PyMol to assess similarity in the lactogenic system. Daily and cumulative milk production and pre-treatment (control) and post-treatment (three drugs) in rabbits were recorded and evaluated by analysing protein, fat, lactose, solid non-- fat, and ash values. All parameters were recorded on the 0th day and at the end of weeks 1, 2, and 3. Mammary gland histopathology was performed to evaluate the effects on mammary glands.

Results: Homology studies revealed that the sequences of the human and rabbit prolactin genes, receptors, and hormones had a high similarity index. Treatment with Domperidone, Metoclopramide, and Shatavari significantly enhanced milk production by enhancing prolactin secretion; only Shatavari increased milk nutrition. Enlargement of the tubuloalveolar ducts of the mammary glands was observed.

Conclusion: Our findings suggest that rabbits are robust, reproducible, ethically superior, and preclinically relevant animals for assessing lactogenic activity.

Klotho, an anti-aging protein, plays a vital role in diverse biological functions, such as regulating calcium and vitamin D levels, preventing chronic fibrosis, acting as an antioxidant and anti-inflammatory agent, safeguarding against cardiovascular and neurodegenerative conditions, as well as exerting anti-apoptotic, anti-senescence effects. Additionally, it contributes to metabolic processes associated with diabetes and exhibits anti-cancer properties. This protein is commonly expressed in organs, such as kidneys, brain, pancreas, parathyroid glands, ovaries, and testes. Recent research has highlighted its significance in human fertility. This narrative review provides insight into the involvement of Klotho protein in male and female fertility, as well as its potential role in managing human infertility in the future. In this study, a search was conducted on literature spanning from November 1997 to June 2024 across multiple databases, including PUBMED, SCOPUS, and Google Scholar, focusing on Klotho proteins. The search utilized keywords, such as "discovery of Klotho proteins," "Biological functions of Klotho," "Klotho in female fertility," "Klotho and PCOS," "Klotho and cryopreservation," and "Klotho in male infertility." Inclusion criteria comprised full-length original or review articles, as well as abstracts, discussing the role of Klotho protein in human fertility, published in English in various peer-reviewed journals. Exclusion criteria involved articles published in languages other than English. Hence, due to its anti-aging characteristics, Klotho protein presents potential roles in male and female fertility and holds promising prospects for reproductive medicine. Further, it holds the potential to become a valuable asset in addressing infertility concerns for both males and females.