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Fish & Shellfish Immunology Sep 2023Di (2-ethylhexyl) phthalate (DEHP) is a neuroendocrine disruptor that can cause multi-tissue organ damage by inducing oxidative stress. Evodiamine (EVO) is an indole...
Di (2-ethylhexyl) phthalate (DEHP) is a neuroendocrine disruptor that can cause multi-tissue organ damage by inducing oxidative stress. Evodiamine (EVO) is an indole alkaloid with anti-inflammatory, antitumor, and antioxidant pharmacological activity. In this manuscript, the effects of DEHP and EVO on the pyroptosis, necroptosis and immunology of grass carp hepatocytes (L8824) were investigated using DCFH-DA staining, PI staining, IF staining, AO/EB staining, LDH kit, qRT-PCR and protein Western blot. The results showed that DEHP exposure upregulated reactive oxygen species (ROS) levels, promoted the expression of TLR4/MyD88/NF-κB pathway, increased the expression of genes involved in cell pyroptosis pathway (LDH, NLRP3, ASC, caspase1, IL-1β, IL-18 and GSDMD) and necroptosis-related genes (RIPK1, RIPK3 and MLKL). The expression of DEHP can also affect immune function, which can be demonstrated by variationsin the activation of antimicrobial peptides (LEAP2, HEPC, and β-defensin) and inflammatory cytokines (TNF-α, IL-2, IL-6 and IL-10). EVO regulates cellular antioxidant capacity by inhibiting ROS burst, reduces DEHP-induced cell pyroptosis and necroptosis to some extent, and restores cellular immune function, after co-exposure with EVO. The TLR4 pathway was inhibited by the co-treatment of TLR4 inhibitor TLR-IN-C34 and DEHP, which attenuated the expression of cell pyroptosis, necroptosis, and immunosuppression. Thus, DEHP induced pyroptosis, necroptosis and abnormal immune function in L8824 cells by activating TLR4/MyD88/NF-κB pathway. In addition, EVO has a therapeutic effect on DEHP-induced toxic injury. This study further provides a theoretical basis for the risk assessment of plasticizer DEHP on aquatic organisms.
Topics: Animals; NF-kappa B; Reactive Oxygen Species; Pyroptosis; Diethylhexyl Phthalate; Myeloid Differentiation Factor 88; Toll-Like Receptor 4; Antioxidants; Carps; Necroptosis; Hepatocytes; Immunosuppression Therapy
PubMed: 37573970
DOI: 10.1016/j.fsi.2023.108995 -
Frontiers in Plant Science 2023Peanut is a segmental allotetraploid in the section of the genus along with the Section Section has several diploid species along with and . The section comprises... (Review)
Review
Peanut is a segmental allotetraploid in the section of the genus along with the Section Section has several diploid species along with and . The section comprises polyploid species. Several species in the genus are highly tolerant to biotic and abiotic stresses and provide excellent sets of genotypes for studies on differential gene expression. Though there were several studies in this direction, more studies are needed to identify more and more gene combinations. Next generation RNA-seq based differential gene expression study is a powerful tool to identify the genes and regulatory pathways involved in stress tolerance. Transcriptomic and proteomic study of peanut plants under biotic stresses reveals a number of differentially expressed genes such as genes (NBS-LRR, LRR-RLK, protein kinases, MAP kinases), pathogenesis related proteins (PR1, PR2, PR5, PR10) and defense related genes (defensin, F-box, glutathione S-transferase) that are the most consistently expressed genes throughout the studies reported so far. In most of the studies on biotic stress induction, the differentially expressed genes involved in the process with enriched pathways showed plant-pathogen interactions, phenylpropanoid biosynthesis, defense and signal transduction. Differential gene expression studies in response to abiotic stresses, reported the most commonly expressed genes are transcription factors (MYB, WRKY, NAC, bZIP, bHLH, AP2/ERF), LEA proteins, chitinase, aquaporins, F-box, cytochrome p450 and ROS scavenging enzymes. These differentially expressed genes are in enriched pathways of transcription regulation, starch and sucrose metabolism, signal transduction and biosynthesis of unsaturated fatty acids. These identified differentially expressed genes provide a better understanding of the resistance/tolerance mechanism, and the genes for manipulating biotic and abiotic stress tolerance in peanut and other crop plants. There are a number of differentially expressed genes during biotic and abiotic stresses were successfully characterized in peanut or model plants (tobacco or ) by genetic manipulation to develop stress tolerance plants, which have been detailed out in this review and more concerted studies are needed to identify more and more gene/gene combinations.
PubMed: 38023864
DOI: 10.3389/fpls.2023.1275854 -
Current Issues in Molecular Biology Aug 2023After sperm enter the female reproductive tract, the physicochemical and biochemical microenvironment undergoes significant changes. In particular, the large changes in... (Review)
Review
After sperm enter the female reproductive tract, the physicochemical and biochemical microenvironment undergoes significant changes. In particular, the large changes in various ions encountered by sperm may alter the physiology of sperm, ultimately compromising capacitation and fertilization. Thus, the rapid response to environmental variations is vital for sperm functions. For example, Calcium, the most crucial ion for sperm functions, enters into sperm via Ca permeable ion channels. The cation channel of sperm (CatSper) is a sperm-specific, pH-sensitive, and Ca-permeable ion channel. It is responsible for the predominant Ca entry in mammalian sperm and is involved in nearly every event of sperm to acquire fertilizing capability. In addition, CatSper also serves as a pivotal polymodal chemosensor in mammalian sperm by responding to multiple chemical cues. Physiological chemicals (such as progesterone, prostaglandins, β-defensins, and odorants) provoke Ca entry into sperm by activating CatSper and thus triggering sperm functions. Additionally, synthetic and natural chemicals (such as medicines, endocrine disrupting chemicals, drugs of abuse, and antioxidants) affect sperm functions by regulating CatSper-dependent Ca signaling. Therefore, understanding the interactions between CatSper and extracellular ligands sheds light on the mechanisms underlying male infertility and offers innovative diagnostic and treatment approaches. This underscores the importance of CatSper as a crucial regulatory target in male reproduction, linking sperm function with the extracellular environment. In conclusion, this review comprehensively summarizes the relevant studies describing the environmental factors that affect CatSper in humans and rodents.
PubMed: 37754226
DOI: 10.3390/cimb45090442 -
Vestnik Otorinolaringologii 2024Children's and adults' rhinosinusitis are two diseases that have both similarities and differences in anatomy, epidemiology, causes, pathogenesis, diagnosis and...
Children's and adults' rhinosinusitis are two diseases that have both similarities and differences in anatomy, epidemiology, causes, pathogenesis, diagnosis and treatment. At the same rhinosinusitis is one of the most common in otorhinolaryngology's practice, both in children and adults. The of adults paranasal sinuses (PNS) anatomy differs from children's PNS anatomy. Although ostiomeatal complex occlusion is recognized as a major cause of poor ventilation and drainage of the adult paranasal sinuses, it does not have a strong effect on pediatric rhinosinusitis, but adenoids play a key role. Adenoids are bacteria and biofilms reservoirs that cause chronic refractory rhinosinusitis regardless of pharyngeal tonsil size. The prevalence of chronic rhinosinusitis (CRS) is lower in children than in adults. Diagnosis of children's rhinosinusitis is more difficult because nasal cavity endoscopic examination is performed rarely due to the occasional need of general anesthesia during the procedure. Moreover, it's necessary to take into account prevailing etiological role of viruses in ARS at children's age and chronic adenoiditis often accompanies pediatric CRS, which requires attention prescribing medical therapy as the basis of rhinosinusitis treatment. The DysheLORz based on roots is highly effective and safe for children's and adults ARS and CRS treatment, both as monotherapy and in combination with topical steroids and antibiotics. This herbal medicine immunomodulatory effect is mediated mainly by stimulating the production of TNF-α, IL-1, IL-12 and IFN-γ. It activates macrophages and improves their phagocytic activity. IL-12, together with TNF-α, enhances NK and cytotoxic CD8 lymphocytes' activity against infected cells. IL-12 effect on Th1 lymphocytes maturation provides a link between innate and adaptive immunity. This is also increasing MCP-1, IP-10 and MIP-1β chemokines synthesis and decreasing MIP-1α, ENA-78, GROα and IL-8 production in PNS and nasal mucosa. This leads to decrease of neutrophils chemotaxis to the inflammation site, and decline of serine proteases concentration (neutrophils main enzymes), that increases mucous membrane epithelial barrier permeability, reducing bacterial infections risk. Additionally, increases epithelial cells beating cilia frequency and inhibits hemagglutinin and neuraminidase present on influenza virus surface. The drug increases antimicrobial peptides production as defensins, human neutrophil peptides (HNP) and bactericidal permeability-increasing protein (BPI), which is also important for rapid inflammation regression in rhinosinusitis. It causes bacterial adhesion to epithelial cells inhibition, phagocytosis stimulation, nitric oxide (NO) release and oxidative burst. The medicine had a direct effect on and . Based on these data, it is possible to explain the high effectiveness and safety of the drugs based on in ENT organs inflammation treatment, for both adults and children over 1 year old.
Topics: Adult; Humans; Child; Infant; Rhinitis; Rhinosinusitis; Tumor Necrosis Factor-alpha; Sinusitis; Nasal Mucosa; Inflammation; Interleukin-12; Chronic Disease
PubMed: 38506028
DOI: 10.17116/otorino20248901164 -
Fish & Shellfish Immunology Dec 2023Bis(2-ethylhexyl) phthalate (DEHP) is not only a widely used plasticizer but also a common endocrine disruptor that frequently lingers in water, posing a threat to the...
Bis(2-ethylhexyl) phthalate (DEHP) is not only a widely used plasticizer but also a common endocrine disruptor that frequently lingers in water, posing a threat to the health of aquatic organisms. Quercetin (Que) is a common flavonol found in the plant kingdom known for its antioxidant, anti-inflammatory, and immunomodulatory effects. However, it is still unclear whether DEHP can cause pyroptosis and affect the expression of cytokines of grass carp L8824 cells and whether Que has antagonistic effect in this process. In our study, grass carp L8824 cells were treated into four groups after 24 h, namely NC group, DEHP group (1000 μM DEHP), Que group (5 μM Que), and DEHP + Que group (1000 μM DEHP + 5 μM Que). Our results indicate a significant increase in the level of ROS in L8824 cells after exposure to DEHP. DEHP upregulated oxidative stress markers (HO and MDA) and downregulated antioxidant markers (CAT, GSH, SOD, and T-AOC). DEHP also upregulated MAPK and NF-κB signal pathway-related proteins and mRNA expressions (p-p38, p-JNK, p-EPK, and p65). As for cell pyroptosis and its related pathways, DEHP upregulated pyroptosis-related protein and mRNA expressions (GSDMD, IL-1β, NLRP3, Caspase-1, LDH, pro-IL-18, IL-18, and ASC). Finally, DEHP can up-regulated cytokines (IL-6 and TNF-α) expression, down-regulated cytokines (IL-2 and IFN-γ) expression, and antimicrobial peptides (β-defensin, LEAP2, and HEPC). The co-treatment of L8824 cells with DEHP and Que inhibited the activation of the ROS/MAPK/NF-κB axis, alleviated pyroptosis, and restored expression of immune-related indicators. Finally, NAC was applied to reverse intervention of oxidative stress. In summary, Que inhibited DEHP-induced pyroptosis and the influence on cytokine and antimicrobial peptide expression in L8824 cells by regulating the ROS/MAPK/NF-κB pathway. Our results demonstrate the threat to fish health from DEHP exposure and confirmed the harm of DEHP to the aquatic ecological environment and the detoxification effect of Que to DEHP, which provides a theoretical basis for environmental toxicology.
Topics: Animals; NF-kappa B; Cytokines; Antioxidants; Diethylhexyl Phthalate; Reactive Oxygen Species; Quercetin; Interleukin-18; Pyroptosis; Carps; Hydrogen Peroxide; Cell Line; RNA, Messenger
PubMed: 37972744
DOI: 10.1016/j.fsi.2023.109223 -
Journal of Cancer Research and Clinical... Aug 2023Antimicrobial peptides (AMPs) are active molecules in the human innate immune system, that participate in host defense and regulate the inflammation process. Previous...
BACKGROUND
Antimicrobial peptides (AMPs) are active molecules in the human innate immune system, that participate in host defense and regulate the inflammation process. Previous reports have confirmed that antimicrobial peptides play a critical role in carcinogenesis.
OBJECTIVE
The present study aimed to evaluate the correlations between plasma concentrations of AMPs and spectrophotometric parameters of skin color in patients with basal cell carcinoma and compare the results with those of healthy controls.
METHODS
The plasma concentrations of cathelicidin and beta-defensin-2 in 100 patients (50 with skin cancer and 50 healthy control subjects) were measured, and skin color parameters were tested using a DermaSpectrophotometer.
RESULTS
In patients with basal cell carcinoma, the concentrations of cathelicidin and beta-defensin-2 were significantly higher than those in healthy controls. In healthy control patients, when erythema increases, the levels of cathelicidin and beta-defensin-2 also increase. The direction of the relationship is opposite in people with basal cell carcinoma-the concentration of antimicrobial peptides decreases and the level of erythema increases.
CONCLUSION
A significantly higher level of plasma concentrations of cathelicidin and HBD-2 are correspondent to the presence of basal cell carcinoma. Skin cancer modifies the relationship between intensity of skin erythema and the levels of cathelicidin and HBD-2. This can be related to inadequate immunological response in patients with skin cancers. New direction of research may be pioneered in searching for cytokine or mast cells disorders.
Topics: Humans; Cathelicidins; Antimicrobial Cationic Peptides; Antimicrobial Peptides; beta-Defensins; Skin Pigmentation; Carcinoma, Basal Cell; Skin Neoplasms; Erythema
PubMed: 36542158
DOI: 10.1007/s00432-022-04530-z -
Cureus Dec 2023Introduction lipopolysaccharide (Pg-LPS) is one of the crucial virulence factors of periodontitis. Antimicrobial peptides (AMPs) are emerging as alternatives or...
Introduction lipopolysaccharide (Pg-LPS) is one of the crucial virulence factors of periodontitis. Antimicrobial peptides (AMPs) are emerging as alternatives or adjuncts to antibiotics in the treatment of microbial infections. In this study, cytotoxicity, anti-inflammatory activity, anti-oxidative stress, cell cycle analysis, and apoptosis properties of AMP, β-defensin 1, were studied in Pg-LPS-stimulated THP-1 (Tohoku Hospital Pediatrics - 1) cell line. Methods The cytotoxic nature of Pg-LPS and β-defensin 1 was studied by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The cytotoxic effect of β-defensin 1 on Pg-LPS-stimulated THP-1 cells was also studied by the same method. The anti-inflammatory role of β-defensin 1 against cyclooxygenase (COX), lipoxygenase (LOX), myeloperoxidase (MPO), and inducible nitric oxide synthase activities were studied. The anti-oxidative nature of β-defensin 1 was analyzed by measuring reactive oxygen species (ROS) generation by dichlorodihydrofluorescein diacetate (DCFDA) assay. Cell cycle distribution and apoptosis were studied by flow cytometry. The hemolytic nature of β-defensin 1 was predicted using the HemoPred web tool. Results The results of the study demonstrated that Pg-LPS showed dose-dependent cytotoxicity to THP-1 cells. β-Defensin 1 had dose-dependent cytotoxicity to THP-1 cells and showed a protective effect on THP-cells up to 1 µg/mL of Pg-LPS, beyond which cell viability decreased. β-Defensin 1 inhibited COX, LOX, MPO, and inducible nitric oxide synthase activities in a concentration-dependent manner. β-Defensin 1 showed anti-oxidative activity by suppressing the generation of ROS measured through fluorescence intensity. From the cell cycle analysis, it was found that β-defensin 1 was able to reduce the Pg-LPS-induced cell cycle arrest at the G0/G1 phase. From the apoptosis profile, β-defensin 1 was found to increase the live cells when compared to THP-1 cells stimulated only with Pg-LPS, indicating that β-defensin 1 provided a protective role to THP-1 cells. β-Defensin 1 was found to be hemolytic in nature by the HemoPred web tool. Conclusion β-Defensin 1 exerted multifunctional activities and can be considered a promising agent for controlling periodontitis.
PubMed: 38249288
DOI: 10.7759/cureus.50880 -
Frontiers in Plant Science 2023Plant defensins are widely distributed in the leaves, fruits, roots, stems, seeds, and tubers. Research shows that defensin in plants play a significant role in...
Plant defensins are widely distributed in the leaves, fruits, roots, stems, seeds, and tubers. Research shows that defensin in plants play a significant role in physiological metabolism, growth and development. Plant defensins can kill and suppress a variety of pathogenic bacteria. In this study, we understand the phylogenetic relationships, protein characterization, chromosomal localization, promoter and gene structural features of the family through sequence alignment and conserved protein structural domain analysis. A total of 73 gene members in wheat, 15 genes in maize, and 11 genes in rice were identified. A total of 35, 65, and 34 gene members were identified in the genomes of , , and , respectively. and were constructed into pART27 vector with YFP by homologous recombination for subcellular localization analysis. Subcellular localization results showed that and were basically located in the cell membrane and cytoplasm, and was also located in the nucleus. and could inhibit the infection of strain '88069'. The results suggest that may be able to improve disease resistance. The study of wheat defensins will be beneficial for improving wheat yield and provides a theoretical basis for research on resistance to wheat diseases.
PubMed: 37941661
DOI: 10.3389/fpls.2023.1279502 -
Biomolecules Mar 2024Antimicrobial peptides (AMPs), as well as host defense peptides (HDPs), constitute the first line of defense as part of the innate immune system. Humans are known to... (Review)
Review
Antimicrobial peptides (AMPs), as well as host defense peptides (HDPs), constitute the first line of defense as part of the innate immune system. Humans are known to express antimicrobial precursor proteins, which are further processed to generate AMPs, including several types of α/β defensins, histatins, and cathelicidin-derived AMPs like LL37. The broad-spectrum activity of AMPs is crucial to defend against infections caused by pathogenic bacteria, viruses, fungi, and parasites. The emergence of multi-drug resistant pathogenic bacteria is of global concern for public health. The prospects of targeting antibiotic-resistant strains of bacteria with AMPs are of high significance for developing new generations of antimicrobial agents. The 37-residue long LL37, the only cathelicidin family of AMP in humans, has been the major focus for the past few decades of research. The host defense activity of LL37 is likely underscored by its expression throughout the body, spanning from the epithelial cells of various organs-testis, skin, respiratory tract, and gastrointestinal tract-to immune cells. Remarkably, apart from canonical direct killing of pathogenic organisms, LL37 exerts several other host defense activities, including inflammatory response modulation, chemo-attraction, and wound healing and closure at the infected sites. In addition, LL37 and its derived peptides are bestowed with anti-cancer and anti-amyloidogenic properties. In this review article, we aim to develop integrative, mechanistic insight into LL37 and its derived peptides, based on the known biophysical, structural, and functional studies in recent years. We believe that this review will pave the way for future research on the structures, biochemical and biophysical properties, and design of novel LL37-based molecules.
Topics: Humans; Cathelicidins; Antimicrobial Cationic Peptides; Anti-Infective Agents; Wound Healing; Skin
PubMed: 38540740
DOI: 10.3390/biom14030320 -
Virology Journal Mar 2024Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate...
Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate of mutation of H5N1 viruses makes the whole process of designing vaccines extremely challenging. Here, we used an in silico approach to design a multi-epitope vaccine against H5N1 influenza A virus using hemagglutinin (HA) and neuraminidase (NA) antigens. B-cell epitopes, Cytotoxic T lymphocyte (CTL) and Helper T lymphocyte (HTL) were predicted via IEDB, NetMHC-4 and NetMHCII-2.3 respectively. Two adjuvants consisting of Human β-defensin-3 (HβD-3) along with pan HLA DR-binding epitope (PADRE) have been chosen to induce more immune response. Linkers including KK, AAY, HEYGAEALERAG, GPGPGPG and double EAAAK were utilized to link epitopes and adjuvants. This construct encodes a protein having 350 amino acids and 38.46 kDa molecular weight. Antigenicity of ~ 1, the allergenicity of non-allergen, toxicity of negative and solubility of appropriate were confirmed through Vaxigen, AllerTOP, ToxDL and DeepSoluE, respectively. The 3D structure of H5N1 was refined and validated with a Z-Score of - 0.87 and an overall Ramachandran of 99.7%. Docking analysis showed H5N1 could interact with TLR7 (docking score of - 374.08 and by 4 hydrogen bonds) and TLR8 (docking score of - 414.39 and by 3 hydrogen bonds). Molecular dynamics simulations results showed RMSD and RMSF of 0.25 nm and 0.2 for H5N1-TLR7 as well as RMSD and RMSF of 0.45 nm and 0.4 for H5N1-TLR8 complexes, respectively. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) confirmed stability and continuity of interaction between H5N1-TLR7 with the total binding energy of - 29.97 kJ/mol and H5N1-TLR8 with the total binding energy of - 23.9 kJ/mol. Investigating immune response simulation predicted evidence of the ability to stimulate T and B cells of the immunity system that shows the merits of this H5N1 vaccine proposed candidate for clinical trials.
Topics: Animals; Humans; Influenza A Virus, H5N1 Subtype; Epitopes, T-Lymphocyte; Toll-Like Receptor 7; Toll-Like Receptor 8; Epitopes, B-Lymphocyte; Vaccines; Computational Biology; Molecular Docking Simulation; Vaccines, Subunit
PubMed: 38509569
DOI: 10.1186/s12985-024-02337-7