ABSTRACT
Antimicrobial peptides, such as nisin, are proposed as promising agents for cancer treatment. While glycation has been recognized as an effective method for enhancing various physicochemical properties of nisin, its anticancer effects remain unexplored. Therefore, we aimed to assess the anticancer potential of glycated nisin against MDA-MB-231 cells. The MDA-MB cells were treated with increasing concentrations of nisin and glycated nisin for 24, 48, and 72 h. The IC50 values for nisin were higher than those for glycated nisin. Glycated nisin at concentrations of 20 and 40 µg/mL decreased cell viability more than nisin at the same concentrations. The rate of apoptosis in the group treated with 20 µg/mL of nisin was lower compared to other treatment groups, and no significant difference in apoptosis rates was observed at different time points (p > 0.05). However, in the glycated nisin groups with concentrations of 10, 20, and 40 µg/mL, the level of apoptosis was very high after 24 h (73-81% of cells undergoing apoptosis). Overall, our study suggests that glycated nisin exhibits stronger cytotoxic effects on MDA-MB-231 cells, primarily involving the induction of apoptosis. This indicates its potential utilization as an alternative approach to address the issue of drug resistance in cancer cells.
Subject(s)
Apoptosis , Breast Neoplasms , Cell Survival , Nisin , Nisin/pharmacology , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Apoptosis/drug effects , Cell Line, Tumor , Glycosylation/drug effects , Cell Survival/drug effects , Female , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistryABSTRACT
Lactoferrin is an antimicrobial peptide (AMP) playing a pivotal role in numerous biological processes. The primary antimicrobial efficacy of lactoferrin is associated with its N-terminal end, which contains various peptides, such as lactoferricin and lactoferrampin. In this context, our research team has developed a refined chimeric 42-mer peptide known as cLF36 over the past few years. This peptide encompasses the complete amino acid sequence of camel lactoferrampin and partial amino acid sequence of lactoferricin. The peptide's activity against human, avian, and plant bacterial pathogens has been assessed using different biological platforms, including prokaryotic (P170 and pET) and eukaryotic (HEK293) expression systems. The peptide positively influenced the growth performance and intestinal morphology of chickens challenged with pathogen bacteria. Computational methods and in vitro studies showed the peptide's antiviral effects against hepatitis C virus, influenza virus, and rotavirus. The chimeric peptide exhibited higher activity against certain tumor cell lines compared to normal cells, which may be attributed to the peptide's interaction with negatively charged glycosaminoglycans on the surface of tumor cells. Importantly, this peptide exhibited no toxicity against host cells and demonstrated remarkable thermal and protease stability in serum. In conclusion, while our investigations suggest that the chimeric peptide, cLF36, may offer potential as a candidate or complementary option to some available antibiotics, antiviral agents, and chemical pesticides, significant uncertainties remain regarding its cost-effectiveness, as well as its pharmacodynamic and pharmacokinetic characteristics, which require further elucidation.
ABSTRACT
The skin is a dynamic organ with a complex immune network critical for maintaining balance and defending against various pathogens. Different types of cells in the skin, such as mast cells (MCs) and group 2 innate lymphoid cells (ILC2s), contribute to immune regulation and play essential roles in the early immune response to various triggers, including allergens. It is beneficial to dissect cell-to-cell interactions in the skin to elucidate the mechanisms underlying skin immunity. The current manuscript concentrates explicitly on the communication pathways between MCs and ILC2s in the skin, highlighting their ability to regulate immune responses, inflammation, and tissue repair. Furthermore, it discusses how the interactions between MCs and ILC2s play a crucial role in various skin conditions, such as autoimmune diseases, dermatological disorders, and allergic reactions. Understanding the complex interactions between MCs and ILC2s in different skin conditions is crucial to developing targeted treatments for related disorders. The discovery of shared pathways could pave the way for novel therapeutic interventions to restore immunological balance in diseased skin tissues.
Subject(s)
Hypersensitivity , Immunity, Innate , Humans , Lymphocytes , Mast Cells , SkinABSTRACT
BACKGROUND: Recently, immunotherapy has become very hopeful for cancer therapy. Cancer treatment through immunotherapy has excellent specificity and less toxicity than conventional chemoradiotherapy. Pathogens have been used in cancer immunotherapy for a long time. The current study aims to evaluate the possibility of Toxoplasma gondii (T. gondii) as a probable treatment for cancers such as melanoma, breast, ovarian, lung, and pancreatic cancer. RECENT FINDINGS: Nonreplicating type I uracil auxotrophic mutants of T. gondii can stimulate immune responses against tumors by reverse immunosuppression at the cellular level. T. gondii can be utilized to research T helper 1 (Th1) cell immunity in intracellular infections. Avirulent T. gondii uracil auxotroph vaccine can change the tumor's immunosuppression and improve the production of type 1 helper cell cytokines, i.e., Interferon-gamma (IFN-γ) and Interleukin-12 (IL-12) and activate tumor-related Cluster of Differentiation 8 (CD8+) T cells to identify and destroy cancer cells. The T. gondii profilin protein, along with T. gondii secreted proteins, have been found to exhibit promising properties in the treatment of various cancers. These proteins are being studied for their potential to inhibit tumor growth and enhance the effectiveness of cancer therapies. Their unique mechanisms of action make them valuable candidates for targeted interventions in ovarian cancer, breast cancer, pancreatic cancer, melanoma, and lung cancer treatments. CONCLUSION: In summary, the study underscores the significant potential of harnessing T. gondii, including its diverse array of proteins and antigens, particularly in its avirulent form, as a groundbreaking approach in cancer immunotherapy.
Subject(s)
Melanoma , Toxoplasma , Humans , Cytokines , Immunosuppression Therapy , UracilABSTRACT
New therapeutic approaches can significantly impact the control of colorectal cancer (CRC), which is increasing worldwide. In this study, we investigated the potential of targeting viral proteins to combat cancer cells. Specifically, we examined the anticancer potential of the matrix (M) protein of the mumps virus Hoshino strain in SW480 CRC cell lines. To begin, we individually transfected SW480 cells with pcDNA3 plasmids containing the mumps virus M gene. We then investigated the percentage of cell death, caspase activity, and the expression levels of genes involved in apoptosis pathways. Following this, we performed bioinformatics analysis on the M protein to identify any similarities with Bcl-2 family members and their viral homologs. Our diagnostic methods showed that treatment with the mumps M protein induced apoptosis and upregulated the expression and activity of pro-apoptotic proteins in SW480 CRC cells compared to the control and vector groups. Based on our bioinformatics studies, we proposed that the BH3 motif in the M protein may trigger apoptosis in CRC cells by interacting with cellular Bax. Overall, our study showed for the first time that the mumps virus M protein could be considered as a targeted treatment for CRC by inducing apoptotic pathways.
Subject(s)
Colorectal Neoplasms , Mumps virus , Humans , Mumps virus/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Cell Line, Tumor , Proto-Oncogene Proteins c-bcl-2 , Apoptosis/geneticsABSTRACT
Mast cells (MCs) are abundant at sites exposed to the external environment and pathogens. Local activation of these cells, either directly via pathogen recognition or indirectly via interaction with other activated immune cells and results in the release of pre-stored mediators in MC granules. The release of these pre-stored mediators helps to enhance pathogen clearance. While MCs are well known for their protective role against parasites, there is also significant evidence in the literature demonstrating their ability to respond to viral, bacterial, and fungal infections. Vitamin D is a fat-soluble vitamin and hormone that plays a vital role in regulating calcium and phosphorus metabolism to maintain skeletal homeostasis. Emerging evidence suggests that vitamin D also has immunomodulatory properties on both the innate and adaptive immune systems, making it a critical regulator of immune homeostasis. Vitamin D binds to its receptor, called the vitamin D receptor (VDR), which is present in almost all immune system cells. The literature suggests that a vitamin D deficiency can activate MCs, and vitamin D is necessary for MC stabilization. This manuscript explores the potential of vitamin D to regulate MC activity and combat pathogens, with a focus on its ability to fight viruses.
Subject(s)
Mast Cells , Vitamin D , Vitamin D/pharmacology , Immune System , Immunity , VitaminsABSTRACT
Colorectal cancer (CRC) is a common and highly malignant neoplasm, ranking as the fourth most frequent cause of cancer-related deaths worldwide. Recently, non-human oncolytic viruses such as Peste des petits ruminants virus (PPRV) are considered as a potent candidate in the viral therapy of cancer. In the current study, the apoptotic effects of matrix (M) protein of PPRV was investigated on SW480 CRC cells. The M gene was cloned into the pcDNA™3.1/Hygro(+) expression vector and transfected into the cancer cells. The cytotoxic effects of the M protein on SW480 cells were confirmed using MTT assay. Furthermore, flow cytometry results showed that the M protein induces apoptosis in 91 % of CRC cells. Interestingly, the expression of the M gene in SW480 cells led to the up-regulation of genes including Bax, p53, and Caspase-9, as well as an increase in the Bax/Bcl-2 ratio. By using bioinformatics modeling, we hypothesized that the M protein could interact with Bax factor through its BH3-like motif and could further activate the intrinsic apoptosis pathway. Ultimately, this study provided the first evidence of the pro-apoptotic activity of PPRV M protein indicating its possible development as a promising novel anti-cancer agent.
Subject(s)
Colorectal Neoplasms , Peste-des-Petits-Ruminants , Peste-des-petits-ruminants virus , Animals , Humans , Peste-des-petits-ruminants virus/genetics , bcl-2-Associated X Protein/genetics , Apoptosis , GoatsABSTRACT
Given the development of drug-resistant cancer cells, designing alternative approaches for cancer treatment seems essential. In this study, we evaluated the anti-tumor effects of nisin A and Newcastle disease virus (NDV) on triple-negative MDA-MB-231 cell line. The MDA-MB-231 cell line was separately and in combination subjected to the different concentrations of a Vero-adapted NDV (JF820294.1) and nisin A. The oncolytic effects of these treatments were analyzed by different cytotoxic and apoptosis techniques including trypan blue staining, MTT assay, acridine orange (EB/AO) staining, colony assay and flow cytometry over time. Nisin A at doses of more than 20.00 µg mL-1 could represent the anti-viral effects and interfere with the oncolytic activity of NDV. Moreover, the analyses indicated that the anti-proliferative and cytotoxic features of combination therapy were stronger than those of individual NDV groups. However, the most apoptotic effect was seen in NDV experimental groups. Taken together, the results from cytotoxicity tests, flow cytometry and colony assay showed that either of the oncolytic agents had significant effects at low concentrations 72 hr post-treatment. Thereby, they had the potential to be used as new approaches in cancer treatment.
ABSTRACT
BACKGROUND: Bovine immunodeficiency virus (BIV) is a member of the Retroviridae family causing a progressive lifelong infection in cattle and buffaloes. OBJECTIVE: Despite the worldwide distribution of the virus, the studies concerning the prevalence of BIV in buffalo populations have not been conducted in Iran as yet. METHODS: The BIV proviral DNA was surveyed in 120 whole blood samples of water buffaloes in southwestern Iran. Nested PCR was employed to amplify a 298-bp fragment of the pol gene. The BIV Pol sequence was detected in 9.1% of the samples. Among PCR-positive samples, two amplified fragments were confirmed by nucleotide sequencing. RESULTS AND CONCLUSIONS: The studied sequences were completely identical to each other and had more than 98%-99% nucleotide homology to R-29 and HXB3 sequences previously deposited in GenBank. Some point mutations that caused coding substitutions were observed in the studied isolates, compared to other strains. A phylogenetic tree was generated based on the BIV Pol nucleotide sequences reported from other countries. All the BIV strains originated from a unique main cluster and then separated from each other over time. This is the first report on the molecular detection of BIV infections in water buffalo populations in Iran. The wide distribution of BIV in different countries including Iran indicates the importance of the infection as it relates to animal health. Although buffaloes show greater resistance to diseases, they should be considered a health risk to cattle. Furthermore, BIV has negative effects on buffalo milk production and can predispose them to secondary infections. Hence, the findings of this study can advance our understanding of the occurrence of BIV infection in Iran, which can play an important role in the distribution of the disease worldwide.
Subject(s)
Cattle Diseases , Immunodeficiency Virus, Bovine , Lentivirus Infections , Animals , Buffaloes , Cattle , Cattle Diseases/epidemiology , Immunodeficiency Virus, Bovine/genetics , Iran/epidemiology , Lentivirus Infections/epidemiology , Lentivirus Infections/veterinary , Nucleotides , PhylogenyABSTRACT
Evidence suggests that neutrophils exert specialized effector functions during infection and inflammation, and that these cells can affect the duration, severity, and outcome of the infection. These functions are related to variations in phenotypes that have implications in immunoregulation during viral infections. Although the complexity of the heterogeneity of neutrophils is still in the process of being uncovered, evidence indicates that they display phenotypes and functions that can assist in viral clearance or augment and amplify the immunopathology of viruses. Therefore, deciphering and understanding neutrophil subsets and their polarization in viral infections is of importance. In this review, the different phenotypes of neutrophils and the roles they play in viral infections are discussed. We also examine the possible ways to target neutrophil subsets during viral infections as potential anti-viral treatments.
Subject(s)
Neutrophils , Virus Diseases , Humans , Immunity , Inflammation/pathology , Neutrophils/pathology , Virus Diseases/pathology , Virus Diseases/therapyABSTRACT
A cytokine storm is an abnormal discharge of soluble mediators following an inappropriate inflammatory response that leads to immunopathological events. Cytokine storms can occur after severe infections as well as in non-infectious situations where inflammatory cytokine responses are initiated, then exaggerated, but fail to return to homeostasis. Neutrophils, macrophages, mast cells, and natural killer cells are among the innate leukocytes that contribute to the pathogenesis of cytokine storms. Neutrophils participate as mediators of inflammation and have roles in promoting homeostatic conditions following pathological inflammation. This review highlights the advances in understanding the mechanisms governing neutrophilic inflammation against viral and bacterial pathogens, in cancers, and in autoimmune diseases, and how neutrophils could influence the development of cytokine storm syndromes. Evidence for the destructive potential of neutrophils in their capacity to contribute to the onset of cytokine storm syndromes is presented across a multitude of clinical scenarios. Further, a variety of potential therapeutic strategies that target neutrophils are discussed in the context of suppressing multiple inflammatory conditions.
Subject(s)
Autoimmune Diseases/immunology , Cytokine Release Syndrome , Cytokines/immunology , Inflammation/immunology , Neoplasms/immunology , Animals , Humans , Immunity, Innate , Neutrophils/cytology , Neutrophils/immunologyABSTRACT
Influenza viruses have affected the world for over a century, causing multiple pandemics. Throughout the years, many prophylactic vaccines have been developed for influenza; however, these viruses are still a global issue and take many lives. In this paper, we review influenza viruses, associated immunological mechanisms, current influenza vaccine platforms, and influenza infection, in the context of immunocompromised populations. This review focuses on the qualitative nature of immune responses against influenza viruses, with an emphasis on trained immunity and an assessment of the characteristics of the host-pathogen that compromise the effectiveness of immunization. We also highlight innovative immunological concepts that are important considerations for the development of the next generation of vaccines against influenza viruses.