Understanding Platelet Thrombogenicity Cascade Of The Biodegradable Chitosan Derivatives In Von Willebrand Disease In Vitro

Biobahan kitosan diperolehi daripada cengkerang hidupan laut mempunyai potensi yang besar bagi kegunaan klinikal kerana ia dapat bertindak balas dengan sel-sel platelet secara bebas untuk membantu proses pembekuan darah. Penyelidikan ini mengesahkan keupayaan biobahan kitosan untuk merangsangkan mekanisma platelet dari penderma darah normal dan pesakit von Willebrand disease (vWD) in vitro. Chitosan has become one of the most promising local hemostatic agents because it is of particular interest as it functions independently on platelets and normal clotting mechanisms. The present study was designed with the aim to test the ability of the mechanisms of blood platelets towards the action of biodegradable chitosan in normal donors and von Willebrand disease (vWD) patients in vitro

Expression of P-selectin, TXA2, TGF-β1 and PDGF-AB in the Presence of Bioadhesive Chitosan Derivatives

Chitosan is a natural macromolecular polysaccharide, derived from chitin extracted from the exoskeleton of some marine invertebrates. This study was designed to evaluate the expression of P-selectin, thromboxane A2 (TXA2), transforming growth factor-β1 (TGF- β1) and platelet derived growth factor-AB (PDGF-AB) using enzyme-linked immunosorbent assays (ELISAs). The chitosan derivatives utilized were 7% N,Ocarboxymethylchitosan (NO-CMC) (with 0.45 mL collagen), 8% NO-CMC, oligo - chitosan (O-C) and oligo -chitosan 53 (O-C 53). We found that O-C showed a significantly superior effect compared to NO-CMC in achieving hemostasis. Post-hoc multiple comparisons using Scheffe test indicated that p-values between the mean differences of all the assayed chitosan derivatives were not significant. However, our analyses successfully identified distinctions between the O-C and NO-CMC test groups and blood alone. These results may expand the understanding of the ability of chitosan derivatives to promote inflammatory responses and angiogenesis depending on their physical and chemical structure

Report on von Willebrand Disease in Malaysia

BACKGROUND: Von Willebrand disease (vWD) is an inherited hemostatic disorder that affects the hemostasis pathway. The worldwide prevalence of vWD is estimated to be 1% of the general population but only 0.002% in Malaysia.AIM: Our present paper has been written to disclose the statistical counts on the number of vWD cases reported from 2011 to 2013.MATERIAL AND METHODS: This article is based on sociodemographic data, diagnoses and laboratory findings of vWD in Malaysia. A total of 92 patients were reported to have vWD in Malaysia from 2011 to 2013.RESULTS: Sociodemographic-analysis revealed that 60% were females, 63% were of the Malay ethnicity, 41.3% were in the 19-44 year old age group and 15.2% were from Sabah, with the East region having the highest registered number of vWD cases. In Malaysia, most patients are predominately affected by vWD type 1 (77.2%). Factor 8, von Willebrand factor: Antigen and vWF: Collagen-Binding was the strongest determinants in the laboratory profiles of vWD.CONCLUSION: This report has been done with great interest to provide an immense contribution from Malaysia, by revealing the statistical counts on vWD from 2011-2013

Hybrid Derivative of Cathelicidin and Human Beta Defensin-2 Against Gram-Positive Bacteria: A Novel Approach for the Treatment of Bacterial Keratitis

Bacterial keratitis (BK) is a major cause of corneal blindness globally. This study aimed to develop a novel class of antimicrobial therapy, based on human-derived hybrid host defense peptides (HyHDPs), for treating BK. HyHDPs were rationally designed through combination of functional amino acids in parent HDPs, including LL-37 and human beta-defensin (HBD)-1 to -3. Minimal inhibitory concentrations (MICs) and time-kill kinetics assay were performed to determine the concentration- and time-dependent antimicrobial activity and cytotoxicity was evaluated against human corneal epithelial cells and erythrocytes. In vivo safety and efficacy of the most promising peptide was examined in the corneal wound healing and Staphylococcus aureus (ATCC SA29213) keratitis murine models, respectively. A second-generation HyHDP (CaD23), based on rational hybridization of the middle residues of LL-37 and C-terminal of HBD-2, was developed and was shown to demonstrate good efficacy against methicillin-sensitive and methicillin-resistant S. aureus [MIC = 12.5–25.0 μg/ml (5.2–10.4 μM)] and S. epidermidis [MIC = 12.5 μg/ml (5.2 μM)], and moderate efficacy against P. aeruginosa [MIC = 25-50 μg/ml (10.4–20.8 μM)]. CaD23 (at 25 μg/ml or 2× MIC) killed all the bacteria within 30 min, which was 8 times faster than amikacin (25 μg/ml or 20× MIC). After 10 consecutive passages, S. aureus (ATCC SA29213) did not develop any antimicrobial resistance (AMR) against CaD23 whereas it developed significant AMR (i.e. a 32-fold increase in MIC) against amikacin, a commonly used treatment for BK. Pre-clinical murine studies showed that CaD23 (0.5 mg/ml) achieved a median reduction of S. aureus bioburden by 94% (or 1.2 log10 CFU/ml) while not impeding corneal epithelial wound healing. In conclusion, rational hybridization of human-derived HDPs has led to generation of a potentially efficacious and safe topical antimicrobial agent for treating Gram-positive BK, with no/minimal risk of developing AMR

Rationalisation of antifungal properties of α-helical pore-forming peptide, mastoparan B

The high mortality associated with invasive fungal infections, narrow spectrum of available antifungals, and increasing evolution of antifungal resistance necessitate the development of alternative therapies. Host defense peptides are regarded as the first line of defense against microbial invasion in both vertebrates and invertebrates. In this work, we investigated the effectiveness of four naturally occurring pore-forming antimicrobial peptides (melittin, magainin 2, cecropin A, and mastoparan B) against a panel of clinically relevant pathogens, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida glabrata. We present data on the antifungal activities of the four pore-forming peptides, assessed with descriptive statistics, and their cytocompatibility with cultured human cells. Among the four peptides, mastoparan B (MB) displayed potent antifungal activity, whereas cecropin A was the least potent. We show that MB susceptibility of phylogenetically distant non-candida albicans can vary and be described by different intrinsic physicochemical parameters of pore-forming α-helical peptides. These findings have potential therapeutic implications for the design and development of safe antifungal peptide-based drugs.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionThis research was funded by the Singapore Ministry of Health’s National Medical Research Council (NMRC) under its Centre Grant Program—Optimization of Core Platform Technologies for Ocular Research (INCEPTOR)-NMRC/CG/M010/2017, Open Fund—Large Collaborative Grant (OFLCG18May-0028), the SingHealth Foundation (SHF/FG663P/2017) and the Agency for Science, Technology and Research (A*STAR) under its Wound Care Innovation for the Tropics (WCIT) Industry Alignment Fund Pre-Positioning (IAF-PP) grant (H17/01/a0/0K9). The work was also supported by the Singapore Ministry of Education (MOE) Academic Research Fund (AcRF) Tier 1 grants (2020-T1-001-062 and R-148-000-309-114). The APC was funded by R1875/3/2022

Hybrid derivative of cathelicidin and human beta defensin-2 against Gram-positive bacteria: A novel approach for the treatment of bacterial keratitis

10.1038/s41598-021-97821-3SCIENTIFIC REPORTS11