Current protein & peptide science最新文献

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.

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.

Recently, a new type of cow's milk has been commercialized in the markets, called A2 milk. It is derived from a specific allelic composition on chromosome 6. The only difference between A1 and A2 milk results from the polymorphism at the 67 amino acid chain. In this position, A2 milk has a proline amino acid, while A1 milk has a histidine amino acid. Proteins are one of the most important components of milk, especially casein, and have received significant attention as they are the source of bioactive opioid peptides called beta-casomorphin-7. Peptides are released through enzymatic digestion of casein and whey proteins. More precisely, this bioactive peptide is produced by sequential gastrointestinal digestion of bovine A1 variants proteins, while this phenomenon is not present in variant A2. Studies have reported that A1 milk can be harmful to health not only for adults but also for infants and that β-casein A2 becomes a safer choice following the relationship between disease risk and consumption of the beta-casomorphin-7 peptide. Indeed, epidemiological studies suggest that the released beta-casomorphin-7 peptide is a risk factor for the development of diseases in humans, but this has not yet been validated by other studies. In contrast, A2 milk has been suggested as an appropriate substitute for A1 milk since populations consuming milk containing high levels of the A2 beta-casein variant have lower rates of diseases, such as diabetes, coronary heart disease, autism, and schizophrenia.

The COVID-19 outbreak, caused by the SARS-CoV-2 coronavirus, has threatened and taken many lives since the end of 2019. Given the importance of COVID-19 worldwide, since its spread, many research groups have been seeking blood markers that could help to understand the disease establishment and prognosis. Usually, those markers are proteins with a differential accumulation only during infection. Based on that, proteomic studies have played a crucial role in elucidating diseases. Mass spectrometry (MS) is a promising technique in COVID-19 studies, allowing the identification and quantification of proteins present in the plasma or serum of affected patients. It helps us to understand pathological mechanisms, predict clinical outcomes, and develop specific therapies. MS proteomics revealed biomarkers associated with infection, disease severity, and immune response. Plasma or blood serum is easy to collect and store; however, its composition and the higher concentration of proteins (e.g., albumins) shadow the identification of less abundant proteins, which usually are essential markers. So, clean-up approaches such as depletion strategies and fractionating are often required to analyze blood samples, allowing the identification of low-abundant proteins. This review will discuss many proteomic approaches to discovering new plasma biomarkers of COVID-19 employed in recently published studies. The challenges inherent to blood samples will also be discussed, such as sample preparation, data processing, and identifying reliable biomarkers.

Gastric cancer remains one of the leading cancer-related deaths worldwide. Despite the research advances, many challenges persist because the diseases are usually diagnosed at an advanced stage and have a complex treatment protocol. Conventional treatments such as chemotherapy, radiation, and surgery pose several side effects and low efficiency. The growing worldwide interest in herbal products, particularly, their bioactive ingredients, presents a promising prospect for auxiliary or alternative therapies for gastric cancer. In vivo experiments show that the given compounds increase the effectiveness and decrease the cumulative harmful impact of conventional anticancer treatments, which may have additive effects. Furthermore, clinical trials have revealed that phytoconstituents have possible anti-gastric cancer properties in humans. Nonetheless, these encouraging preclinical observations have not progressed into clinical practice all that much due to the absence of adequately powered Phase III trials for GC. Therefore, this review stresses the need for well-controlled human interventions to confirm the effectiveness and safety of herb- based therapies. In the long run, the incorporation of these herbal products could present a new approach to constructing the gastric cancer prevention and treatment outlook while minimizing the side effects of conventional treatments and opening up arenas of functional foods and pharmaceuticals.

Background: Dihydropyrimidinase (DPYS), a pivotal enzyme in the pyrimidine synthesis pathway, has been increasingly studied for its potential role in cancer therapy. While its presence has been noted in various cancers, its specific impact on sarcoma (SARC) still needs to be fully understood.

Objective: This study sought to explore the correlation between DPYS expression and SARC, utilizing data from The Cancer Genome Atlas (TCGA), bioinformatics tools, and experimental validation.

Methods: The study employed statistical analysis and logistic regression to assess the link between DPYS expression levels and clinical features in SARC patients. Survival analysis was conducted using the Kaplan-Meier method and Cox regression, evaluating the prognostic significance of DPYS expression. Gene set enrichment analysis and immuno-infiltration analysis were conducted to uncover the potential regulatory mechanisms of the DPYS gene. We validated the expression of DPYS using GSE17674. Quantitative reverse transcription PCR was utilized to measure DPYS expression levels in SARC cell lines.

Results: The study found that reduced DPYS expression in SARC correlated with therapeutic response (P = 0.011), histological subtype (P = 0.003), and the presence of residual tumor (P = 0.043). Reduced DPYS expression was a predictor of inferior Overall Survival (OS), with a Hazard Ratio (HR) of 0.56 and a 95% Confidence Interval (CI) of 0.37-0.84 (P = 0.005), as well as Disease-Specific Survival (DSS), with an HR of 0.64 and a 95% CI of 0.41-1.00 (P = 0.048). DPYS expression was also identified as an independent factor for OS in SARC (HR: 0.335; 95% CI: 0.169-0.664; P = 0.002). The gene was associated with various pathways, including GPCR ligand binding, signaling by interleukins, G alpha (i) signaling events, Class A/1 Rhodopsin-like receptors, cytokine-cytokine receptor interaction, and platelet activation. DPYS expression also showed a correlation with certain immune cell infiltrates and was found to be significantly downregulated in SARC cell lines.

Conclusion: DPYS may serve as a potential prognostic biomarker and therapeutic target for SARC.

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.

The phenomenon of Liquid-Liquid Phase Separation (LLPS) serves as a vital mechanism for the spatial organization of biomolecules, significantly influencing the elementary processes within the cellular milieu. Intrinsically disordered proteins, or proteins endowed with intrinsically disordered regions, are pivotal in driving this biophysical process, thereby dictating the formation of non-membranous cellular compartments. Compelling evidence has linked aberrations in LLPS to the pathogenesis of various neurodegenerative diseases, underscored by the disordered proteins' proclivity to form pathological aggregates. This study meticulously evaluates the arsenal of contemporary experimental and computational methodologies dedicated to the examination of intrinsically disordered proteins within the context of LLPS. Through a discerning discourse on the capabilities and constraints of these investigative techniques, we unravel the intricate contributions of these ubiquitous proteins to LLPS and neurodegeneration. Moreover, we project a future trajectory for the field, contemplating on innovative research tools and their potential to elucidate the underlying mechanisms of LLPS, with the ultimate goal of fostering new therapeutic avenues for combating neurodegenerative disorders.