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Synthesis of Bioactive Peptides for Pharmaceutical Applications
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Jaison Jeevanandam, Ashish Kumar Solanki, Shailza Sharma, Prabir Kumar Kulabhusan, Sapna Pahil, Michael K. Danquah
Various Gram-negative and Gram-positive bacteria are associated with skin infections and drug-resistant biofilms formations. It has been reported that the human antimicrobial peptide named cathelicidin (LL-37), conjugated with silver nanoparticles inhibits skin infections and controls biofilm formation of P. aeruginosa. Fungal infections of oral cavity, including oral candidiasis were also reported to be curable with low dosages of AMP (Xia et al., 2017). The short synthetic bioactive peptides RRIKA and RR are found to be a potential microbial growth inhibition agent by the disruption of pore formation and bacterial membranes. Further, these peptides were also effective against clinical and drug-resistant isolates of S. aureus that cause skin infections (Pfalzgraff et al., 2018). A peptide (HPA3NT3) isolated from Helicobacter pylori exhibited high antimicrobial activity against Propionibacterium acnes-mediated skin acne. Numerous modified lipopeptides such as Lauryl-KPV-NH2, Palmitoyl-KPV-NH2, and Palmitoyl-KH-NH2 were also described to be efficient in the treatment of bacterial vaginosis, acne vulgaris, candidiasis, and atopic dermatitis (Kang et al., 2017). Recently, two AMPs, namely, Indolicidin and LL-37, were reported to reduce the spread of Herpes Simplex Virus I, which is responsible for fever blisters and cold sores in the face and mouth (Piotrowska et al., 2017).
Nanotherapeutics: Enabling Vitamin D3 as a Multifaceted Nutraceutical
Published in Bhupinder Singh, Minna Hakkarainen, Kamalinder K. Singh, NanoNutraceuticals, 2019
Krantisagar S. More, Vinod S. Ipar, Amit S. Lokhande, Anisha A. D’souza, Padma V. Devarajan
Psoriasis is a common, chronic autoimmune inflammatory skin disorder, characterized by sharply demarcated, erythematous patches or plaques, with potential systemic complications (Soleymani et al., 2015). In psoriatic skin, the erythematous scaling plaques are the result of keratinocyte hyperproliferation and abnormal differentiation. Vitamin D has been known to inhibit keratinocyte proliferation and exerts a selective proapoptotic effect as shown in Figure 11.3. Psoriasis is a disease based on T-cell dysregulation and cytokine dysregulation. During stressed conditions, proinflammatory cytokines (TNF-α, IFN-α, IL-2, and IL-8) induce T cell differentiation into Th1 and Th17 releasing inflammatory cytokines, which cause keratinocyte proliferation (Fu and Vender, 2011; Soleymani et al., 2015). Vitamin D modulates immune cell expression by inhibiting the production of cytokines required for Th1 and Th17 differentiation and stimulate T cells to produce anti-inflammatory Th2 cytokines such as IL-10, thus reducing the production of inflammatory cytokines (IL-2, IL-8, IFN-γ, and TNF-α) in dendritic cells. Vitamin D has also been shown to stimulate the antimicrobial peptide cathelicidin (LL-37) in keratinocytes. Cathelicidin serves as a first-line defense mechanism in the innate immune system and has anti-inflammatory effects. Cathelicidin is upregulated during wound healing and tissue repair. A study demonstrated that topical application of calcitriol and calcipotriol on psoriatic lesions induced Th2 differentiation and inhibited IL-12/23 production, with upregulation of cathelicidin (Fu and Vender, 2011; Soleymani et al., 2015).
Epigenotoxicity: a danger to the future life
Published in Journal of Environmental Science and Health, Part A, 2023
Farzaneh Kefayati, Atoosa Karimi Babaahmadi, Taraneh Mousavi, Mahshid Hodjat, Mohammad Abdollahi
A matched case-control study including 244 cases with knee OA and its matched controls reported that some DNMTs polymorphisms like rs2424913 of DNMT3B are responsible for the etiology of OA; thus, the footprint of DNA methylation and epigenetic pathways was proved.[205] Another primary research showed that upregulation of the cathelicidin antimicrobial peptide (CAMP) gene due to its hypo DNA methylation results in chondrocytes apoptosis through suppression of ROS levels and inflammatory responses. Therefore, it is really important in the pathogenesis of OA.[150] Chondrogenesis is an essential part of cartilage development. During this process, the H3K27me3 biomarker is reduced due to the upregulation of kdm6b histone deacetylase. It has been reported that altered expression of kdm6b dysregulates the chondrogenesis process and results in OA pathogenesis.[151] Recent studies showed that methylation of the IL-β promoter reduces this cytokine and causes OA through inflammatory pathways. Increased DNA methylation and decreased histone acetylation of the SOX9 gene resulted in the downregulation of this gene in advanced OA.[206]
Functional expression, purification, and antimicrobial activity of a novel antimicrobial peptide MLH in Escherichia coli
Published in Preparative Biochemistry and Biotechnology, 2018
Guo-Li Gong, Yuan Wei, Zhong-Zhong Wang
The mature peptide part of musca domestica cecropin (Md-Cec) consists of 40 amino acid residues, including two α-helixes, a hydrophobic C-terminal rich in glycine residues, and an amidated and alkline N-terminal which plays a major role in its bioactivity and preventing carboxypeptidase hydrolysis.[91011] LL-37 is the only amphipathic α-helix structure antimicrobial peptide in Cathelicidin family and found in humans to date, being the cutting product of Cathelicidin peptide Hcap-18′s C-terminal and was named as LL-37 due to the 37 amino acid residues in its mature peptide zone. LL-37 is susceptible to host or bacterial proteases and its central part (residue 13–34) could form typical amphipathic helix structure.[121314] Helicobacter pylori antibacterial peptide (Hp) is a short peptide (2–20) located in L1N terminal of Helicobacter pylori’s ribosomal protein, being highly homologous with cecropins, it has stronger antimicrobial activity against Gram-negative bacteria.[15,16] Although there are many reports about heterozygous peptides, no study about heterozygous peptides from Md-Cec, LL-37, and Hp peptide was reported. Therefore in this study, fragments of Md-Cec, LL-37, and Hp peptides were combined to design genes for the heterozygous peptide. Three primers were designed using SOE-PCR and target gene MLH was obtained by two rounds of amplifications. The target gene was connected to expression vector pET-32a (+), and the connected genes were transformed to Escherichia coli for constructing pET-32a-MLH/BL21 (DE3), a gene engineering bacterium. Fermentation conditions were optimized to obtain the highly expressed fusion proteins, which were then purified and renaturated. Finally, heterozygous peptides’ activity was assessed by agarose hole diffusion method.