Generating a Peptide Library Using the Repeats of Amino Acid Scaffolds Created by Sliding the Framework of a 7-mer Human Chemerin Segment and Discovery of Potent Antibacterial and Antimycobacterial Peptides.

The quest for new approaches for generating novel bioactive designer proteins/peptides has continued with their success in various biomedical applications. Previously, we designed a 14-mer α-helical peptide with antimicrobial and antimycobacterial activities by employing a tandem repeat of the 7-mer, "KVLGRLV" human chemerin segment. Herein, we devised a new method of "sliding framework" with this segment to create amino acid scaffolds of varying sizes and sequences and explored the design of a peptide library with antibacterial and antimycobacterial activities.

Innovative Strategies and Methodologies in Antimicrobial Peptide Design.

Multiple lines of research have led to the hypothesis that antimicrobial peptides (AMPs) are an important component of the innate immune response, playing a vital role in the defense against a wide range of infectious diseases. In this review, we explore the occurrence and availability of antimicrobial proteins and peptides across various species, highlighting their natural abundance and evolutionary significance. The design of AMPs has been driven by the identification of key structural and functional features, which are essential for optimizing their antimicrobial activity and reducing toxicity to host cells.

Corannulene Amino Acid-Derived Water-Soluble Amphiphilic Buckybowls as Broad-Spectrum Membrane Targeting Antibacterial Agents.

To date, the use of corannulene has been restricted in the area of material science, but its application in biomedical research has yet to be established due to its nonsolubility in an aqueous environment and synthetic infeasibility. Herein, we detail the development of a new family of highly curved π-conjugated corannulene-containing unnatural α-amino acid (CAA) derivatives to overcome this challenge. These CAAs have been extended as novel constituents for the synthesis of corannulene-containing water-soluble cationic peptides (CCPs), which display inhibitory activity against broad-spectrum pathogenic bacteria along with drug-resistant bacteria via a membrane-damaging mechanism.

Myofibrosarcoma of Maxilla - Case Report and Review of Literature.

Myofibrosarcoma is a distinct mesenchymal malignancy which commonly occurs in head and neck region. It has a high tendency for local recurrence and distant metastasis. 39-year-old male presented with epistaxis, nasal obstruction and left sided complete loss of vision.

Robotic Neck Dissection in Head and Neck Cancer via Modified BABA Technique.

Introduction: Neck dissection forms an important component in the surgical management of head and neck cancers. By using the conventional techniques of neck dissection, a conspicuous scar is inevitable for the patients. The development of robotic assisted neck dissection provides for a scar-free neck along with good oncological and functional outcomes.

Evaluation of Pharmacokinetic and Pharmacodynamic (PK/PD) of Novel Fluorenylmethoxycarbonyl- Phenylalanine Antimicrobial Agent.

Objective: To assess the pharmacokinetic profile, in-vivo toxicity, and efficacy of 9-Fluorenylmethoxycarbonyl-L-phenylalanine (Fmoc-F) as a potential antibacterial agent, with a focus on its suitability for clinical translation.

Methods: An RP-HPLC-based bio-analytical method was developed and qualified to quantify Fmoc-F levels in mouse plasma for pharmacokinetic analysis. Oral bioavailability was determined, and in-vivo toxicity was evaluated following intra-peritoneal administration.

Extraskeletal Myxoid Chondrosarcoma of Floor of Mouth-A Rare Case Report and Review of Literature.

Introduction: Chondrosarcomas are rare malignancies of the cartilage and myxoid chondrosarcoma is its variant which commonly occurs in soft tissue of extremities. Extraskeletal chondrosarcoma is a rare malignant neoplasm of bone or soft tissue origin and is characterized by the presence of spindle cells admixed with well differentiated cartilage or chondroid stroma. They are mostly radioresistant tumours and surgical resections with adequate margins is considered as the ideal treatment modality with adjuvant radiotherapy in high grade tumours and add on chemotherapy, in case of presence of poor prognostic factors.

10-Residue MyD88-Peptide Adopts β-Sheet Structure, Self-Assembles, Binds to Lipopolysaccharides, and Rescues Mice from Endotoxin-Mediated Lung-Infection and Death.

Naturally occurring cationic antimicrobial peptides (AMPs) mostly adopt α-helical structures in bacterial membrane mimetic environments. To explore the design of novel β-sheet AMPs, we identified two short cationic amphipathic β-strand segments from the crystal structure of the innate immune protein, MyD88. Interestingly, of these, the 10-residue arginine-valine-rich synthetic MyD88-segment, KRCRRMVVVV (M3), exhibited β-sheet structure when bound to the outer membrane Gram-negative bacterial component, LPS.

Spermine-Conjugated Short Proline-Rich Lipopeptides as Broad-Spectrum Intracellular Targeting Antibacterial Agents.

Toward the design of new proline-rich peptidomimetics, a short peptide segment, present in several proline-rich antimicrobial peptides (AMPs), was selected. Fatty acids of varying lengths and spermine were conjugated at the N- and C-terminals of the peptide, respectively. Spermine-conjugated lipopeptides, C-PR-Spn and C-PR-Spn, exhibited minimum inhibitory concentrations within 1.

Self-Assembling Nano-Globular Peptide from Human Lactoferrin Acts as a Systemic Enhancer of Bone Regeneration: A Novel Peptide for Orthopedic Application.

A technology for systemic and repeated administration of osteogenic factors for orthopedic use is an unmet medical need. Lactoferrin (∼80 kDa), present in milk, is known to support bone growth. We discovered a lactoferrin-mimetic peptide, LP2 (an 18-residue fragment from the N-terminus of the N-lobe of human lactoferrin), which self-assembles into a nano-globular assembly with a β-sheet structure in an aqueous environment.

A Noncytotoxic Temporin L Analogue with Antibacterial and Antiendotoxin Activities and a Nonmembrane-Lytic Mode of Action.

Cytotoxic frog antimicrobial peptide Temporin L (TempL) is an attractive molecule for the design of lead antimicrobial agents due to its short size and versatile biological activities. However, noncytotoxic TempL variants with desirable biological activities have rarely been reported. TempL analogue Q3K,TempL is water-soluble and possesses a significant antiendotoxin property along with comparable cytotoxicity to TempL.

A collagen domain-derived short adiponectin peptide activates APPL1 and AMPK signaling pathways and improves glucose and fatty acid metabolisms.

Adiponectin is a fat tissue-derived adipokine with beneficial effects against diabetes, cardiovascular diseases, and cancer. Accordingly, adiponectin-mimetic molecules possess significant pharmacological potential. Oligomeric states of adiponectin appear to determine its biological activity.

Understanding variation in chronic disease outcomes.

We propose an explanation for variation in disease outcomes based on patient adaptation to the conditions of chronic disease. We develop a model of patient adaptation using the example of Type 2 diabetes mellitus and assumptions about the process entailed in transforming self-care behaviors of compliance with treatment, compliance with glucose monitoring, and patient's knowledge seeking behavior into health outcomes of glycemic control and patient satisfaction. Using data from 609 adults with diagnosed Type 2 diabetes we develop an efficiency (fitness) frontier in order to identify best practice (maximally adapted) patients and forms (archetypes) of patient inefficiency.