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.
View Article and Find Full Text PDFFormononetin (FNT) has limited application due to poor water solubility and substantial phase II metabolism. In the present study, we used phospholipid complex (PC) containing FNT and UDP-glucuronosyltransferase (UGT1A1) inhibitor piperine (PIP) to overcome FNT limitations. We characterized and compared both FNT-PC and FNT-PIP-PC complexes.
View Article and Find Full Text PDFThe implementation of the laser sintering for inkjet-printed nanoparticles and metal organic decomposition (MOD) inks on a flexible polymeric film has been analyzed in detail. A novel approach by implementing, next to a commonly 3.2 mm diameter spot laser optic, a line laser optic with a laser beam area of 2 mm × 80 mm, demonstrates the high potential of selective laser sintering to proceed towards a fast and efficient sintering methodology in printed electronics.
View Article and Find Full Text PDFThe Apicomplexa phylum encompasses numerous obligate intracellular parasites, some associated with severe implications for human health, including Plasmodium, Cryptosporidium, and Toxoplasma gondii. The iron-sulfur cluster [Fe-S] biogenesis ISC pathway, localized within the mitochondrion or mitosome of these parasites, is vital for parasite survival and development. Previous work on T.
View Article and Find Full Text PDFTo 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.
View Article and Find Full Text PDFThe present study aimed at identifying the genetic mutation responsible for teratozoospermic infertility in a case with coiled sperm tails. A 33-year-old infertile male was diagnosed with teratozoospermic infertility, with sperm head in coiled (HIC) tail as the most common deformity. We employed whole exome sequencing to identify the genetic cause in this case.
View Article and Find Full Text PDFLeishmaniasis is a neglected tropical disease (endemic in 99 countries) caused by parasitic protozoa of the genus Leishmania. As treatment options are limited, there is an unmet need for new drugs. The hydroxynaphthoquinone class of compounds demonstrates broad-spectrum activity against protozoan parasites.
View Article and Find Full Text PDFMycobacterium tuberculosis (Mtb), causative agent of tuberculosis (TB) and non-tubercular mycobacterial (NTM) pathogens such as Mycobacterium abscessus are one of the most critical concerns worldwide due to increased drug-resistance resulting in increased morbidity and mortality. Therefore, focusing on developing novel therapeutics to minimize the treatment period and reducing the burden of drug-resistant Mtb and NTM infections are an urgent and pressing need. In our previous study, we identified anti-mycobacterial activity of orally bioavailable, non-cytotoxic, polycationic phosphorus dendrimer 2G0 against Mtb.
View Article and Find Full Text PDFGenome-wide association studies in inflammatory bowel disease have identified risk loci in the orosomucoid-like protein 3/ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) gene to confer susceptibility to ulcerative colitis (UC), but the underlying functional relevance remains unexplored. Here, we found that a subpopulation of the UC patients who had higher disease activity shows enhanced expression of ORMDL3 compared to the patients with lower disease activity and the non-UC controls. We also found that the patients showing high ORMDL3 mRNA expression have elevated interleukin-1β cytokine levels indicating positive correlation.
View Article and Find Full Text PDFMyeloid differentiation factor 2 (MD2), the TLR4 coreceptor, has been shown to possess opsonic activity and has been implicated in phagocytosis and intracellular killing of Gram-negative bacteria. However, any MD2 protein segment involved in phagocytosis of Gram-negative bacteria is not yet known. A short synthetic MD2 segment, MD54 (amino acid regions 54 to 69), was shown to interact with a Gram-negative bacterial outer membrane component, LPS, earlier.
View Article and Find Full Text PDFObjectives: To compare predictive significance of sarcopenia and clinical frailty scale (CFS) in terms of postoperative mortality in patients undergoing emergency laparotomy METHODS: In compliance with STROCSS statement standards, a retrospective cohort study with prospective data collection approach was conducted. The study period was between January 2017 and January 2022. All adult patients with non-traumatic acute abdominal pathology who underwent emergency laparotomy in our centre were included.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
February 2024
Arbortristoside-A (Arbor-A) is a naturally occurring iridoid glycoside and herbal-based lead molecule with proven medicinal potential. Aiming at the development of an efficient analytical tool for the quantification of Arbor-A in pharmaceutical dosage forms, in the presented work, we developed an economical, fast, and sensitive RP-HPLC-UV method and validated the procedure as per the ICH guidelines, Q2(R1). The chromatographic separation was accomplished under the optimised experimental conditions using an HPLC system with an LC-2010 autosampler, a PDA detector, and a Phenomenex C18 column with the mobile phase composed of a 70:30 (v/v) water-acetonitrile mixture eluting isocratically at a flow rate of 1 mL/min at ambient temperature, and UV detection at 310 nm.
View Article and Find Full Text PDFBackground: Hepatocellular carcinoma (HCC) continues to pose a significant health challenge and is often diagnosed at advanced stages. Metabolic reprogramming is a hallmark of many cancer types, including HCC and it involves alterations in various metabolic or nutrient-sensing pathways within liver cells to facilitate the rapid growth and progression of tumours. However, the role of STAT3-NFκB in metabolic reprogramming is still not clear.
View Article and Find Full Text PDFReplication of the malarial parasite in human erythrocytes requires massive zinc fluxes, necessitating the action of zinc transporters across the parasite plasma and organellar membranes. Although genetic knockout studies have been conducted on a few "orphan" zinc transporters in spp., none of them have been functionally characterized.
View Article and Find Full Text PDFBackground The National Emergency Laparotomy Audit (NELA) mortality risk score is currently used in the UK to estimate mortality risk after emergency laparotomy. The HAS (Hajibandeh Index, American Society of Anesthesiologists status, and sarcopenia) is a novel model with excellent accuracy in predicting the risk of mortality after emergency laparotomy. This study aimed to compare the predictive performance of the HAS model and NELA score in estimating mortality risk following emergency laparotomy.
View Article and Find Full Text PDFIn the present investigation, we have strategically synthesized Glutathione (GSH) stimuli-sensitive analogues using carbamate linkers (CL) of DOX (DOX-CL) and RB (RB-CL) which were then anchored to gold nanoparticles (Au-DOX-CL, Au-RB-CL) using mPEG as a spacer. It was observed that carbamate linkage (CL) with four carbon spacer is critical, to position the terminal thiol group, to access the carbamate group efficiently to achieve GSH-assisted release of DOX and RB in tumor-specific environment. When assessed for GSH reductase activity in MDA-MB 231 cell lines, Au-DOX-CL and Au-RB-CL showed nearly 4.
View Article and Find Full Text PDFThe most prevalent clinical option for treating cancer is combination chemotherapy. In combination therapy, assessment and optimization for obtaining a synergistic ratio could be obtained by various preclinical setups. Currently, in vitro optimization is used to get synergistic cytotoxicity while constructing combinations.
View Article and Find Full Text PDFTowards identification of novel therapeutic candidates, a series of quinazolinone-based acetamide derivatives were synthesized and assessed for their anti-leishmanial efficacy. Amongst synthesized derivatives, compounds F12, F27 and F30 demonstrated remarkable activity towards intracellular L. donovani amastigotes in vitro, with IC values of 5.
View Article and Find Full Text PDFAltered mitochondrial function without a well-defined cause has been documented in patients with ulcerative colitis (UC). In our efforts to understand UC pathogenesis, we observed reduced expression of clustered mitochondrial homolog (CLUH) only in the active UC tissues compared with the unaffected areas from the same patient and healthy controls. Stimulation with bacterial Toll-like receptor (TLR) ligands similarly reduced CLUH expression in human primary macrophages.
View Article and Find Full Text PDFThe present research was designed to develop a nanoemulsion (NE) of triphenylphosphine-D-α-tocopheryl-polyethylene glycol succinate (TPP-TPGS) and paclitaxel (PTX) to effectively deliver PTX to improve breast cancer therapy. A quality-by-design approach was applied for optimization and and characterization were performed. The TPP-TPGS-PTX-NE enhanced cellular uptake, mitochondrial membrane depolarization and GM cell cycle arrest compared with free-PTX treatment.
View Article and Find Full Text PDFObjectives: To develop and validate a predictive model to predict the risk of postoperative mortality after emergency laparotomy taking into account the following variables: age, age ≥ 80, ASA status, clinical frailty score, sarcopenia, Hajibandeh Index (HI), bowel resection, and intraperitoneal contamination.
Summary Background Data: The discriminative powers of the currently available predictive tools range between adequate and strong; none has demonstrated excellent discrimination yet.
Methods: The TRIPOD and STROCSS statement standards were followed to protocol and conduct a retrospective cohort study of adult patients who underwent emergency laparotomy due to non-traumatic acute abdominal pathology between 2017 and 2022.
According to WHO, to combat the resistant strains, new effective anti-microbial agents are needed on an urgent basis and global researchers should focus their efforts and discovery programs on developing them against antibiotic-resistant pathogens or priority pathogens like ESKAPE. In this context, Cationic antimicrobial peptides (AMPs) are being explored extensively as promising next-generation antimicrobials due to their broad range, fast kinetics and multifunctional role. Despite recent advances, it is still a daunting challenge to identify and design a potent AMP with no cytotoxicity, but with broad specific antimicrobial activity, stability and efficacy under conditions in a cost-effective and robust manner.
View Article and Find Full Text PDFOwing to its ability to induce cellular senescence, inhibit PCNA, and arrest cell division cycle by negatively regulating CDKs as well as being a primary target of p53, p21 is traditionally considered a tumor suppressor. Nonetheless, several reports in recent years demonstrated its pro-oncogenic activities such as apoptosis inhibition by cytosolic p21, stimulation of cell motility, and promoting assembly of cyclin D-CDK4/6 complex. These opposing effects of p21 on cell proliferation, supported by the observations of its inconsistent expression in human cancers, led to the emergence of the concept of "antagonistic duality" of p21 in cancer progression.
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