Current protein & peptide science最新文献

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.

Platinum (II) drugs, including cisplatin, carboplatin, and oxaliplatin, have achieved significant clinical success in cancer treatment. However, their clinical application has been greatly hindered by various adverse factors such as non-specific activation and drug resistance. Compared with Pt(II) drugs, the axial ligands within Pt(IV) compounds can improve the pharmacokinetic properties, selectivity, and biological activity, implementing alternative cytotoxic mechanisms beyond DNA cross-linking and partially overcoming drug resistance. The controlled conversion of Pt(IV) prodrugs into Pt(II) agents at the tumor site has been extensively explored internationally. In this review, Pt(IV) prodrug modification strategies are first summarized, next the development of the predominant external and internal photosensitizers is listed. Finally, three representative photoreduction mechanisms and strategies for developing corresponding Pt(IV) prodrugs are discussed. This work provides constructive instruction for the subsequent molecular design of Pt(IV) prodrugs.

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 SDS-- PAGE, 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.

Background: Chemotherapy is the mainstay of cancer treatment, bringing patients optimism about recurrence and survival. However, the clinical effectiveness of chemotherapeutic drugs is frequently jeopardized by their intrinsic toxicity, resulting in side effects affecting the quality of life of cancer patients. This analysis explores the ethnopharmacological impact of phytopharmaceuticals, highlighting their traditional use in many cultures. The present study, which takes its cues from indigenous knowledge, aims to close the knowledge gap between traditional medicine and modern medicine in reducing the toxicities of chemotherapy treatments.

Aim: The present in-depth study aims to highlight the current research and upcoming developments in phytopharmaceuticals for reducing the toxicity of chemotherapeutic drugs. Further, we address the mechanisms through which phytopharmaceuticals may reduce chemotherapy-induced side effects that include nausea, vomiting, myelosuppression, nephropathy, neuropathy, and cardiotoxicity using data from a variety of preclinical and clinical investigations.

Materials and methods: The literature search was carried out by employing search engines such as PubMed and Google Scholar with keywords such as cancer, chemotherapy, CNS toxicity, hematopoietic toxicity, renal toxicity, GI toxicity, CNS toxicity, and phytopharmaceuticals.

Results: Bioactive chemicals found in plants, such as fruits, vegetables, herbs, and spices, are being studied for their capacity to improve the safety and acceptability of chemotherapy regimens. The current review also dives into the investigation of phytopharmaceuticals as adjuvant medicines in cancer treatment, which is a viable path for addressing the pressing need to lessen chemotherapy-induced toxicities.

Conclusion: The present review revealed that the potential of phytopharmaceuticals in alleviating chemotherapeutic drug toxicities would pave the way for better cancer treatment and patient outcomes, harmonizing with the larger trend towards personalized and holistic approaches to chemotherapy.

Unconventional Post-Translational Modifications (PTMs) have gained increasing attention as crucial players in cancer development and progression. Understanding the role of unconventional PTMs in cancer has the potential to revolutionize cancer diagnosis, prognosis, and therapeutic interventions. These modifications, which include O-GlcNAcylation, glutathionylation, crotonylation, including hundreds of others, have been implicated in the dysregulation of critical cellular processes and signaling pathways in cancer cells. This review paper aims to provide a comprehensive analysis of unconventional PTMs in cancer as diagnostic markers and therapeutic targets. The paper includes reviewing the current knowledge on the functional significance of various conventional and unconventional PTMs in cancer biology. Furthermore, the paper highlights the advancements in analytical techniques, such as biochemical analyses, mass spectrometry and bioinformatic tools etc., that have enabled the detection and characterization of unconventional PTMs in cancer. These techniques have contributed to the identification of specific PTMs associated with cancer subtypes. The potential use of Unconventional PTMs as biomarkers will further help in better diagnosis and aid in discovering potent therapeutics. The knowledge about the role of Unconventional PTMs in a vast and rapidly expanding field will help in detection and targeted therapy of cancer.

Background: Antibiotic resistance is one of the main concerns of public health, and the whole world is trying to overcome such a challenge by finding novel therapeutic modalities and approaches. This study has applied the sequence hybridization approach to the original sequence of two cathelicidin natural parent peptides (BMAP-28 and LL-37) to design a novel HLM peptide with broad antimicrobial activity.

Methods: The physicochemical characteristics of the newly designed peptide were determined. As well, the new peptide's antimicrobial activity [Minimum Inhibitory Concentration (MIC), Minimum Bacterial Eradication Concentration (MBEC), and antibiofilm activity] was tested on two control (Staphylococcus aureus ATCC 29213, Escherichia Coli ATCC 25922) and two resistant [Methicillin-resistant Staphylococcus aureus (MRSA) ATCC BAA41, New Delhi metallo-beta- lactamase-1 Escherichia coli ATCC BAA-2452) bacterial strains. Furthermore, synergistic studies have been applied to HLM-hybridized peptides with five conventional antibiotics by checkerboard assays. Also, the toxicity of HLM-hybridized peptide was studied on Vero cell lines to obtain the IC50 value. Besides the percentage of hemolysis action, the peptide was tested in freshly heparinized blood.

Results: The MIC values for the HLM peptide were obtained as 20, 10, 20, and 20 μM, respectively. Also, the results showed no hemolysis action, with low to slightly moderate toxicity action against mammalian cells, with an IC50 value of 10.06. The Biomatik corporate labs, where HLM was manufactured, determined the stability results of the product by Mass Spectrophotometry (MS) and High-performance Liquid Chromatography (HPLC) methods. The HLM-hybridized peptide exhibited a range of synergistic to additive antimicrobial activities upon combination with five commercially available different antibiotics. It has demonstrated the biofilm-killing effects in the same concentration required to eradicate the control strains.

Conclusion: The results indicated that HLM-hybridized peptide displayed a broad-spectrum activity toward different bacterial strains in planktonic and biofilm forms. It showed synergistic or additive antimicrobial activity upon combining with commercially available different antibiotics.

The distortion of the cellular membrane transport pathway has a profound impact on cell dynamics and can drive serious physiological consequences during the process of cell sorting. SNX17 is a member of the Sorting Nexin (SNX) family and plays a crucial role in protein sorting and transport in the endocytic pathway. SNX17, SNX27, and SNX31 belong to the SNX-FERM subfamily and possess the FERM domain, which can assist in endocytic transport and lysosomal degradation. The binding partners of SNX27 have been discovered to number over 100, and SNX27 has been linked to the development of Alzheimer's disease progression, tumorigenesis, cancer progression, and metastasis. However, the role and potential mechanisms of SNX17 in human health and disease remain poorly understood, and the function of SNX17 has not been fully elucidated. In this review, we summarize the structure and basic functions of SNX protein, focusing on providing current evidence of the role and possible mechanism of SNX17 in human neurodegenerative diseases and cardiovascular diseases.