{"title":"Intercellular Interactions Mediated by HGF And TGF-Β Promote the 3D Spherical and Xenograft Growth of Liver Cancer Cells.","authors":"Zheng Peng, Xiaolan Lv, Pengfei Zhang, Qiao Chen, Hongyu Zhang, Jianlin Chen, Xingxuan Ma, Bohui Ouyang, Meng Hao, Haibo Tong, Dongwei Guo, Yi Luo, Shigao Huang","doi":"10.2174/1389203724666230825100318","DOIUrl":"10.2174/1389203724666230825100318","url":null,"abstract":"<p><strong>Background: </strong>Recently, the importance of the interactions between liver cancer cells and fibroblasts has been increasingly recognized; however, many details remain to be explored.</p><p><strong>Methods: </strong>In this work, we first studied their intercellular interactions using conditioned medium from mouse embryonic fibroblasts (MEFs), then through a previously established coculture model.</p><p><strong>Results: </strong>Culturing in a conditioned medium from MEFs could significantly increase the growth, migration, and invasion of liver cancer cells. The coculture model further demonstrated that a positive feedback loop was formed between transforming growth factor-β (TGF-β) from HepG2 cells and mHGF (mouse hepatocyte growth factor) from MEFs during coculture. In this feedback loop, c-Met expression in HepG2 cells was significantly increased, and its downstream signaling pathways, such as Src/FAK, PI3K/AKT, and RAF/MEK/ERK, were activated. Moreover, the proportion of activated MEFs was also increased. More importantly, the growth-promoting effects caused by the interaction of these two cell types were validated <i>in vitro</i> by a 3D spheroid growth assay and <i>in vivo</i> by a xenograft mouse model.</p><p><strong>Conclusion: </strong>Collectively, these findings provide valuable insights into the interactions between fibroblasts and liver cancer cells, which may have therapeutic implications for the treatment of liver cancer.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"71-82"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10111453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Comprehensive Review on the Significance of Cysteine in Various Metabolic Disorders; Particularly CVD, Diabetes, Renal Dysfunction, and Ischemic Stroke.","authors":"Namra Aziz, Pranay Wal, Rishika Sinha, Prashant Ramesh Shirode, GunoSindhu Chakraborthy, Mukesh Chandra Sharma, Pankaj Kumar","doi":"10.2174/0113892037287215240424090908","DOIUrl":"10.2174/0113892037287215240424090908","url":null,"abstract":"<p><p>Metabolic disorders have long been a challenge for medical professionals and are a leading cause of mortality in adults. Diabetes, cardiovascular disorders (CVD), renal dysfunction, and ischemic stroke are the most prevalent ailments contributing to a high mortality rate worldwide. Reactive oxygen species are one of the leading factors that act as a fundamental root cause of metabolic syndrome. All of these disorders have their respective treatments, which, to some degree, sabotage the pathological worsening of the disease and an inevitable death. However, they pose a perilous health hazard to humankind. Cysteine, a functional amino acid shows promise for the prevention and treatment of metabolic disorders, such as CVD, Diabetes mellitus, renal dysfunction, and ischemic stroke. In this review, we explored whether cysteine can eradicate reactive oxygen species and subsequently prevent and treat these diseases.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"682-707"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bile Acids as Signaling Molecules: Role of Ursodeoxycholic Acid in Cholestatic Liver Disease.","authors":"Eduardo Cifuentes-Silva, Claudio Cabello-Verrugio","doi":"10.2174/1389203724666230818092800","DOIUrl":"10.2174/1389203724666230818092800","url":null,"abstract":"<p><p>Ursodeoxycholic acid (UDCA) is a natural substance physiologically produced in the liver. Initially used to dissolve gallstones, it is now successfully used in treating primary biliary cirrhosis and as adjuvant therapy for various hepatobiliary cholestatic diseases. However, the mechanisms underlying its beneficial effects still need to be clarified. Evidence suggests three mechanisms of action for UDCA that could benefit humans with cholestatic liver disease (CLD): protection of cholangiocytes against hydrophobic bile acid (BA) cytotoxicity, stimulation of hepatobiliary excretion, and protection of hepatocytes against BA-induced apoptosis. These mechanisms may act individually or together to potentiate them. At the molecular level, it has been observed that UDCA can generate modifications in the transcription and translation of proteins essential in the transport of BA, correcting the deficit in BA secretion in CLD, in addition to activating signaling pathways to translocate these transporters to the sites where they should fulfill their function. Inhibition of BA-induced hepatocyte apoptosis may play a role in CLD, characterized by BA retention in the hepatocyte. Thus, different mechanisms of action contribute to the improvement after UDCA administration in CLD. On the other hand, the effects of UDCA on tissues that possess receptors that may interact with BAs in pathological contexts, such as skeletal muscle, are still unclear. This work aims to describe the main molecular mechanisms by which UDCA acts in the human body, emphasizing the interaction in tissues other than the liver.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"206-214"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Swati Tyagi, Srabani Kar, Amit Srivastava, Pratyoosh Shukla
{"title":"Protein Engineering in Cyanobacterial Biotechnology: Tools and Recent Updates.","authors":"Swati Tyagi, Srabani Kar, Amit Srivastava, Pratyoosh Shukla","doi":"10.2174/1389203724666230822100104","DOIUrl":"10.2174/1389203724666230822100104","url":null,"abstract":"<p><p>Cyanobacteria have emerged as a microbial cell factory to produce a variety of bioproducts, including peptides and proteins. Cyanobacteria stand out among other organisms due to their photoautotrophic metabolism and ability to produce a wide range of metabolites. As photoautotrophic hosts can produce industrial compounds and proteins by using minimal resources such as sunlight, atmospheric carbon dioxide, and fewer nutrients, cyanobacteria are cost-effective industrial hosts. Therefore, the use of protein engineering tools for rational protein design, and the desired modification of enzyme activity has become a desirable undertaking in cyanobacterial biology. Protein engineering can improve their biological functions as well as the stability of their intracellular proteins. This review aims to highlight the success of protein engineering in the direction of cyanobacterial biotechnology and outlines the emerging technologies, current challenges, and prospects of protein engineering in cyanobacterial biotechnology.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"95-106"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10041969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zohreh Salimi, Mehdi Rostami, Yaser Eshaghi Milasi, Alireza Mafi, Ramin Raoufinia, Amirhossein Kiani, Fariba Sakhaei, Behrooz Ghezelbash, Alexandra E Butler, Maryam Mohammad-Sadeghipour, Amirhossein Sahebkar
{"title":"Unfolded Protein Response Signaling in Hepatic Stem Cell Activation in Liver Fibrosis.","authors":"Zohreh Salimi, Mehdi Rostami, Yaser Eshaghi Milasi, Alireza Mafi, Ramin Raoufinia, Amirhossein Kiani, Fariba Sakhaei, Behrooz Ghezelbash, Alexandra E Butler, Maryam Mohammad-Sadeghipour, Amirhossein Sahebkar","doi":"10.2174/1389203724666230822085951","DOIUrl":"10.2174/1389203724666230822085951","url":null,"abstract":"<p><p>Frequent exposure to various external and internal adverse forces (stresses) disrupts cell protein homeostasis through endoplasmic reticulum (ER) capacity saturation. This process leads to the unfolded protein response (UPR), which aims to re-establish/maintain optimal cellular equilibrium. This complex mechanism is involved in the pathogenesis of various disorders, such as metabolic syndrome, fibrotic diseases, neurodegeneration, and cancer, by altering cellular metabolic changes integral to activating the hepatic stellate cells (HSCs). The development of hepatic fibrosis is one of the consequences of UPR activation. Therefore, novel therapies that target the UPR pathway effectively and specifically are being studied. This article covers the involvement of the UPR signaling pathway in cellular damage in liver fibrosis. Investigating the pathogenic pathways related to the ER/UPR stress axis that contribute to liver fibrosis can help to guide future drug therapy approaches.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"59-70"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10051372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An Update on Dipeptidyl Peptidase-IV Inhibiting Peptides.","authors":"Sachithanantham Annapoorani Sivaraman, Varatharajan Sabareesh","doi":"10.2174/0113892037287976231212104607","DOIUrl":"10.2174/0113892037287976231212104607","url":null,"abstract":"<p><p>Diabetes is a chronic metabolic disorder. According to the International Diabetes Federation, about 537 million people are living with diabetes. The two types of diabetes are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), among which the population affected by T2DM is relatively higher. A major reason for T2DM is that insulin stimulation is hampered due to the inactivation of incretin hormones. Dipeptidyl peptidase-IV (DPP-IV) is a serine protease that is directly involved in the inactivation of incretin hormones, e.g., glucagon-like peptide-1 (GLP-1). Therefore, the inhibition of DPP-IV can be a promising method for managing T2DM, in addition to other enzyme inhibition strategies, such as inhibition of α-amylase and α -glucosidase. Currently, about 12 different gliptin drugs are available in the market that inhibit DPP-IV in a dose-dependent manner. Instead of gliptins, 'peptides' can also be employed as an alternative and promising way to inhibit DPP-IV. Peptide inhibitors of DPP-IV have been identified from various plants and animals. Chemically synthesized peptides have also been experimented for inhibiting DPP-IV. Most peptides have been analysed by biochemical assays, whereas some <i>in vitro</i> assays have also been reported. Molecular docking analysis has been applied to comprehend the mechanism of inhibition. In this review, certain aspects of natural as well as synthetic peptides are described that have been proven to inhibit DPP-IV.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"267-285"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Majed M Masadeh, Haneen Alshogran, Mohammad Alsaggar, Salsabeel H Sabi, Enaam M Al Momany, Majd M Masadeh, Nasr Alrabadi, Karem H Alzoubi
{"title":"Evaluation of Novel HLM Peptide Activity and Toxicity against Planktonic and Biofilm Bacteria: Comparison to Standard Antibiotics.","authors":"Majed M Masadeh, Haneen Alshogran, Mohammad Alsaggar, Salsabeel H Sabi, Enaam M Al Momany, Majd M Masadeh, Nasr Alrabadi, Karem H Alzoubi","doi":"10.2174/0113892037291252240528110516","DOIUrl":"10.2174/0113892037291252240528110516","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (<i>Staphylococcus aureus</i> ATCC 29213, <i>Escherichia coli</i> ATCC 25922) and two resistant (Methicillin-resistant <i>Staphylococcus aureus</i> (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 IC<sub>50</sub> value. Besides the percentage of hemolysis action, the peptide was tested in freshly heparinized blood.</p><p><strong>Results: </strong>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 IC<sub>50</sub> 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"826-843"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the Potential Role of Phytopharmaceuticals in Alleviating Toxicities of Chemotherapeutic Agents.","authors":"Ujwal N Katolkar, Sanjay J Surana","doi":"10.2174/0113892037307940240606075208","DOIUrl":"10.2174/0113892037307940240606075208","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"753-779"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yasmim A Grangeiro, Ana L E Santos, Flávia E V Barbosa, Renato R Roma, Racquel O S Souza, Cláudio G L Silva, Claudener S Teixeira
{"title":"A Review of the Leishmanicidal Properties of Lectins.","authors":"Yasmim A Grangeiro, Ana L E Santos, Flávia E V Barbosa, Renato R Roma, Racquel O S Souza, Cláudio G L Silva, Claudener S Teixeira","doi":"10.2174/0113892037275751231221053730","DOIUrl":"10.2174/0113892037275751231221053730","url":null,"abstract":"<p><p>Lectins are proteins widely distributed among plants, animals and microorganisms that have the ability to recognize and interact with specific carbohydrates. They have varied biological activities, such as the inhibition of the progression of infections caused by fungi, bacteria, viruses and protozoa, which is related to the interaction of these proteins with the carbohydrates present in the cell walls of these microorganisms. Leishmaniasis are a group of endemic infectious diseases caused by protozoa of the genus <i>Leishmania. In vitro</i> and <i>in vivo</i> tests with promastigotes and amastigotes of <i>Leishmania</i> demonstrated that lectins have the ability to interact with glycoconjugates present on the cell surface of the parasite, it prevents their development through various mechanisms of action, such as the production of ROS and alteration of membrane integrity, and can also interact with defense cells present in the human body, thus showing that these molecules can be considered alternative pharmacological targets for the treatment of leishmaniasis. The objective of the present work is to carry out a bibliographic review on lectins with leishmanicidal activity, emphasizing the advances and perspectives of research in this theme. Through the analysis of the selected studies, we were able to conclude that lectins have great potential for inhibiting the development of leishmaniasis. However, there are still few studies on this subject.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"443-453"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Oluwatobi Otun, Richard Graca, Ikechukwu Achilonu
{"title":"Combating Aminoglycoside Resistance: From Structural and Functional Characterisation to Therapeutic Challenges with RKAAT.","authors":"Sarah Oluwatobi Otun, Richard Graca, Ikechukwu Achilonu","doi":"10.2174/0113892037278814231226104509","DOIUrl":"10.2174/0113892037278814231226104509","url":null,"abstract":"<p><p>A comprehensive knowledge of aminoglycoside-modifying enzymes (AMEs) and their role in bacterial resistance mechanisms is urgently required due to the rising incidence of antibiotic resistance, particularly in <i>Klebsiella pneumoniae</i> infections. This study explores the essential features of AMEs, including their structural and functional properties, the processes by which they contribute to antibiotic resistance, and the therapeutic importance of aminoglycosides. The study primarily examines the Recombinant <i>Klebsiella pneumoniae</i> Aminoglycoside Adenylyl Transferase (RKAAT), particularly emphasizing its biophysical characteristics and the sorts of resistance it imparts. Furthermore, this study examines the challenges presented by RKAAT-mediated resistance, an evaluation of treatment methods and constraints, and options for controlling infection. The analysis provides a prospective outlook on strategies to address and reduce antibiotic resistance. This extensive investigation seeks to provide vital insights into the continuing fight against bacterial resistance, directing future research efforts and medicinal approaches.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"454-468"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}