Current protein & peptide science最新文献

Migraine is a neurological disease that, while not inherently causing "chronic headaches," can evolve into a chronic condition over time including major symptoms such as nausea, and light, sound, and allodynia, particularly in cases of frequent episodic migraine or due to factors such as medication overuse or inadequate management. This condition's complex pathophysiology makes treatment difficult. Genetics, trigeminovascular system activation, and cortical spreading depression are involved. Epidemiological research estimates that one in seven persons worldwide are affected, mostly women. Migraine prevalence has increased dramatically in recent decades; however, it varies by demographic and location. This review covers pharmaceutical and non-pharmacological migraine therapy methods and their future. Second-generation triptans have reduced side effects and administration issues, however, Zolmitriptan and Sumatriptan still treat migraines. Monoclonal antibodies that target calcitonin gene-related peptides may prevent migraines; however, their accessibility and safety are problems. Antiepileptics, beta-blockers, and neuromodulation devices are also available. Wearable technology offers customized monitoring and intervention. Precision medicine and gene-based medicines provide hope for tailored migraine treatments, but access, privacy, and informed consent raises ethical concerns. Stakeholder engagement must promote patient autonomy and well-being, responsible implementation, and equal access to novel therapies. A holistic and multidisciplinary approach is needed to manage migraines, taking into consideration present and future therapy developments and new challenges. Research, collaboration, and ethics can improve migraine outcomes and quality of life.

Background: Gastric cancer has become one of the major diseases threatening human health. This study aimed to investigate the mechanism of an anticancer bioactive peptide (ACBP) combined with oxaliplatin (OXA) on MKN-45, SGC7901, and NCI-N87 differentiated human gastric cancer cells and GES-1 immortalized human gastric mucosal epithelial cells. The therapeutic effect and action mechanism of short-term intermittent ACBP combined with OXA on nude mice with human gastric cancer were also investigated.

Methods: The half-maximal inhibitory concentrations of these agents in these cells were measured by an MTT assay, and cell morphological changes were observed by H&E staining. The expression of Lin28, miR-107, miR-609, and Let-7 in these four cell lines was determined by q-PCR after drug treatment. Lin28 protein expression in these four cell lines treated with these drugs was measured by western blotting. Furthermore, activity and quality of life were observed daily in all tumor-bearing nude mice, and the expression of Lin28 in tumor tissue was determined by immunohistochemistry and RT-PCR.

Results: The results showed that ACBP inhibited the proliferation of MKN-45, SGC7901, and NCI-N87 gastric cancer cells in a dose-dependent manner and weakly suppressed the proliferation of GES-1 cells. Moreover, its inhibitory effect on proliferation was stronger in poorly differentiated gastric cancer cells. ACBP, OXA, and the combination upregulated Lin28 gene expression in MKN-45 cells and downregulated it in SGC7901 and GES-1 cells. ACBP and the combination therapy downregulated Let-7 expression in MKN-45 cells and upregulated Let-7 expression in SGC7901 cells. The combination of ACBP with OXA demonstrated significant anticancer sensitization. Moreover, it also significantly improved the quality of life of tumor-bearing nude mice and reduced the toxic side effects of chemotherapeutic drugs on nude mice.

Conclusion: ACBP alone and in combination with oxaliplatin influenced the expression of tumor stem cell marker gene Lin28 and regulated the expression of microRNAs specifically regulated by Lin28. In addition, the anticancer effects and attenuated sensitization effects of ACBP may be related to the Lin28/miRNA-107 signaling pathway, acting by inhibiting the proliferation of cancerous stem cells. The findings of this study provide a scientific basis for exploring the antitumor mechanism of ACBP alone and combined with chemotherapeutic drugs.

Background: Actinomycetes, Gram-positive bacteria, are recognized for producing bioactive metabolites. Lonar Soda Lake, an alkaline ecosystem, hosts diverse actinomycetes with possible anticancer activities.

Aim: To assess the cytotoxic potential of fermentation metabolites from actinomycetes isolated from Lonar Soda Lake against HeLa cancer cells employing in-vitro and in-silico methods.

Objectives: Evaluate the cytotoxicity of fermentation metabolites from Lonar Lake actinomycetes on HeLa cells. Execute molecular docking to forecast metabolite connections with cancer-related proteins.

Materials and methods: The actinomycetes were isolated from the sediment sample of Lonar Lake using a selective medium and recognized by gene sequencing. Cytotoxicity on HeLa cells was assessed using the MTT assay, in consort with oxidative stress and apoptotic markers (GSH, MDA, TNF-α, and caspase 3). Molecular docking and molecular dynamics studies evaluated metabolite binding to cancer-related proteins (Bcl-2, TNF-α, caspase 3).

Results: Fermentation metabolites of three Lonar Lake Sediment isolates (LLSD), LLSD-5, LLSD- 7, and LLSD-9 showing promising cytotoxic activity against HeLa cell lines by MTT assay, also significantly modulate the oxidative stress parameters (GSH, MDA), and cell apoptotic marker (TNF-α, caspase 3). IC50 values were 82.9 μg/ml (LLSD-5), 162.3 μg/ml (LLSD-7), and 20.15 μg/ml (LLSD-9). Furthermore, molecular docking displayed robust binding affinities to cancer-related proteins, uncovering the possible mechanism of action.

Conclusion: The fermentation metabolites actinomycete isolates from Lonar Lake exhibit significant cytotoxic activity against HeLa cancer cell lines. Both in-vitro and in-silico analyses support the potential of these metabolites as anticancer agents.

Introduction: Ex vivo preconditioning increases the therapeutic potential of mesenchymal stem cells (MSCs) in terms of antioxidant activity, growth factor production, homing, differentiation, and immunomodulation. Therefore, it is considered an effective strategy to be used before transplantation and therapeutic application of MSCs. Histone deacetylase inhibitor (HDACi), valproic acid (VPA), has been reported to induce hepatic differentiation in MSCs. Although individual studies have shown that preconditioning and epigenetic modification enhance the survival and differentiation of MSCs, the combined effects of these therapies have not been fully explored. This study aims to investigate the combined effect of hydrogen peroxide (H2O2) preconditioning and HDACi (valproic acid) on the differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) into hepatic-like cells.

Methods: MSCs were first preconditioned with H2O2 and then cultured with VPA. The migration and proliferation potential of the treated cells were evaluated using wound healing and colony-- forming unit assays. Furthermore, the expression of hepatic genes (FOXA2, CK8, CK18, TAT) and proteins (AFP, ALB, TAT) was evaluated in all treated groups.

Results: The combined therapy group exhibited enhanced cell migration and proliferation, as evidenced by wound healing and colony-forming unit assays. Additionally, the combined treatment group showed higher expression of FOXA2, CK8, and CK18 hepatic genes and TAT protein, suggesting an improved differentiation of stem cells into hepatocytes.

Conclusion: In conclusion, the combination of H2O2 and VPA emerges as an important factor in promoting hepatocyte differentiation. However, further studies are required to optimize this protocol for future therapeutics.

Stroke is an acute cerebrovascular disease that causes brain tissue damage due to sudden blockage or rupture of blood vessels in the brain. According to the latest data from the Global Burden of Disease Study, the number of stroke patients worldwide is estimated to exceed 100 million, and more than 80% of patients suffer from stroke. Ischemic stroke is a type of stroke due to which two-thirds of the patients are disabled or even die, seriously affecting the patient's quality of life. Lactate is an indispensable substance in various physiological and pathological cells and plays a regulatory role in different aspects of energy metabolism and signal transduction. Studies have found that during cerebral ischemia and hypoxia, lactate concentration increases significantly, improving the energy supply to the ischemic area. Based on the scientific concept of lactate travelling through the brain, this article focuses on the important role of lactate as an energy source after ischemic stroke and analyzes the relationship between lactate as a signaling molecule and neuroprotection, angiogenesis, and anti-inflammatory effects. The aim of this study is to outline the molecular mechanisms by which lactate exerts its different effects in ischemic stroke. Some references are provided in this study for the research on lactate therapy for ischemic stroke.

Neoplastic transformation of B cells of the post-germinative center can lead to oncohematological dyscrasias, which often results in an abnormal production of monoclonal immunoglobulin light chains. The non-physiological production of large amounts of IgG light chains leads to the formation of extracellular deposits called 'aggregomas' and rare conditions such as light chain crystal deposition disease. Kidney manifestations and heavy-chain deposition disease can also occur in plasma cell dyscrasias, emphasizing the role of IgG misfolding and aggregation. This minireview describes molecular mechanisms of IgG light-chain aggregation, as well as the consequences and therapeutic implications of IgG light chain misfolding in these disorders. By elucidating the mechanisms of IgG light chain misfolding and aggregation, researchers can identify specific molecular and cellular pathways. This knowledge opens the door to novel therapeutic targets, offering the potential for interventions that can either prevent the initial misfolding events, promote the proper folding and processing of immunoglobulins, or enhance the clearance of misfolded proteins and aggregates. These protein folding-related issues persist even after the successful elimination of the malignant B cells. Such targeted protein-folding therapies could significantly improve patients' quality of life and contribute to their recovery. Thus, a deep understanding of IgG light chain misfolding and its consequences not only sheds light on the complex biology of oncohematological dyscrasias but also opens the way for innovative treatment strategies that could transform patient care in these conditions, instilling hope and motivation in the healthcare professionals and researchers in this field.

Background: Ganoderma spp. are a great source of bioactive molecules. The production and recovery of bioactive molecules vary according to strain, growth substrate, and extraction solution. Variations in protease and their inhibitors in basidiomata from a commercial strain (G. lingzhi) and an Amazonian isolate (Ganoderma sp.) cultivated in Amazonian lignocellulosic wastes and extracted with different solutions are plausible and were investigated in our study.

Methods: Basidiomata from cultivation in substrates based on açaí seed, guaruba-cedro sawdust and three lots of marupá sawdust were submitted to extraction in water, Tris-HCl, and sodium phosphate. Protein content, proteases, and protease inhibitors were estimated through different assays. The samples were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR).

Results: Tris-HCl provided higher protein extraction from Ganoderma sp. and higher caseinolytic, gelatinolytic, and fibrinolytic activity for G. lingzhi cultivated in açaí. Water extracts of Ganoderma sp., in general, exhibited higher trypsin and papain inhibitor activities compared to G. lingzhi. Extracts in Tris-HCl and sodium phosphate showed more intense protein bands in SDSPAGE, highlighting bands of molecular weights around 100, 50, and 30 kDa. FTIR spectra showed patterns for proteins in all extracts, with variation in transmittance according to substrate and extractor.

Conclusion: Water extract from Amazonian Ganoderma sp. cultivated in marupá wastes are promising as a source of protease inhibitors, while the Tris-HCL extract of G. lingzhi from açaí cultivation stands out as a source of proteases with fibrinolytic, caseinolytic, and gelatinolytic activities.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) is a broad condition characterized by lipid accumulation in the liver tissue, which can progress to fibrosis and cirrhosis if left untreated. Traditionally, liver biopsy is the gold standard for evaluating fibrosis. However, non-invasive biomarkers of liver fibrosis are developed to assess the fibrosis without the risk of biopsy complications. Novel serum biomarkers have emerged as a promising tool for non-invasive assessment of liver fibrosis in MAFLD patients. Several studies have shown that elevated levels of Mac-2 binding protein glycosylation isomer (M2BPGi) are associated with increased liver fibrosis severity in MAFLD patients. This suggests that M2BPGi could serve as a reliable marker for identifying individuals at higher risk of disease progression. Furthermore, the use of M2BPGi offers a non-invasive alternative to liver biopsy, which is invasive and prone to sampling errors. Overall, the usage of M2BPGi in assessing liver fibrosis in MAFLD holds great promise for improving risk stratification and monitoring disease progression in affected individuals. Further research is needed to validate its utility in clinical practice and establish standardized protocols for its implementation.

The biotechnology field has witnessed rapid advancements, leading to the development of numerous proteins and peptides (PPs) for disease management. The production and isolation of bioactive milk peptides (BAPs) involve enzymatic hydrolysis and fermentation, followed by purification through various techniques such as ultrafiltration and chromatography. The nutraceutical potential of bioactive milk peptides has gained significant attention in nutritional research, as these peptides may regulate blood sugar levels, mitigate oxidative stress, improve cardiovascular health, gut health, bone health, and immune responses, and exhibit anticancer properties. However, to enhance BAP bioavailability, the encapsulation method can be used to offer protection against protease degradation and controlled release. This article provides insights into the composition, types, production, isolation, bioavailability, and health benefits of BAPs.