Synthesis of Temporin-SHa Retro Analogs with Lysine Addition/Substitution and Antibiotic Conjugation to Enhance Antibacterial, Antifungal, and Anticancer Activities.

In the face of rising the threat of resistant pathogens, antimicrobial peptides (AMPs) offer a viable alternative to the current challenge due to their broad-spectrum activity. This study focuses on enhancing the efficacy of temporin-SHa derived NST-2 peptide (), which is known for its antimicrobial and anticancer activities. We synthesized new analogs of using three strategies, i.

Through Space π-Electrons Communication in [2,2]-Paracyclophanes: Unprecendented Stabilization of Radicals.

Efforts to understand radical stability have led to considerable progress in radical chemistry. In this article, we investigated a novel approach to enhancing the radical stability of carbon-centered radicals through space electron delocalization within [2,2]-paracyclophanes. Alkoxyamines possessing a paracyclophane scaffold exploit face-to-face π-π-interactions between the aromatic rings to effectively lower bond dissociation energy (BDE) for NO-C bond homolysis.

ZNF143 is a transcriptional regulator of nuclear-encoded mitochondrial genes that acts independently of looping and CTCF.

Gene expression is orchestrated by transcription factors, which function within the context of a three-dimensional genome. Zinc-finger protein 143 (ZNF143/ZFP143) is a transcription factor that has been implicated in both gene activation and chromatin looping. To study the direct consequences of ZNF143/ZFP143 loss, we generated a ZNF143/ZFP143 depletion system in mouse embryonic stem cells.

Optimized prime editing of the Alzheimer's disease-associated APOE4 mutation.

Gene editing strategies to safely and robustly modify the Alzheimer's disease-associated APOE4 isoform are still lacking. Prime editing (PE) enables the precise introduction of genetic variants with minimal unintended editing and without donor templates. However, it requires optimization for each target site and has not yet been applied to APOE4 gene editing.

Engineered PsCas9 enables therapeutic genome editing in mouse liver with lipid nanoparticles.

Clinical implementation of therapeutic genome editing relies on efficient in vivo delivery and the safety of CRISPR-Cas tools. Previously, we identified PsCas9 as a Type II-B family enzyme capable of editing mouse liver genome upon adenoviral delivery without detectable off-targets and reduced chromosomal translocations. Yet, its efficacy remains insufficient with non-viral delivery, a common challenge for many Cas9 orthologues.

Antibacterial Materials: Influence of the Type and Conditions of Biological Tests on the Measured Antibacterial Activity.

In recent years, the growing problem of antibiotic resistance has highlighted the need for antibacterial materials to prevent the development of infections. Different types of tests exist to certify the antibacterial properties of materials. Variations in results can occur due to the unique requirements of each test technique.

Screening of antimicrobial activity in venom: Exploring key parameters.

The escalating challenge of antibiotic resistance significantly threatens global health, underscoring the critical need for new antimicrobial agents. Venoms, increasingly recognized as reservoirs of bioactive compounds with diverse pharmacological effects, have been the focus of recent research. This work evaluates the use of various screening methodologies in assessing the antimicrobial activities of 185 venoms against some gram positive and gram negative bacteria, including E.

Combining culture optimization and synthetic biology to improve production and detection of secondary metabolites in : application to myxoprincomide.

Microbial secondary metabolites play crucial ecological roles in governing species interactions and contributing to their defense strategies. Their unique structures and potent bioactivities have been key in discovering antibiotics and anticancer drugs. Genome sequencing has undoubtedly revealed that myxobacteria constitute a huge reservoir of secondary metabolites as the well-known producers, actinomycetes.

Quaternized 1,2,3-Triazolyl Content and Modulation Potentiate Antibacterial and Antifungal Activities of Amphipathic Peptoids.

Bioinspired from cationic antimicrobial peptides, sequence-defined triazolium-grafted peptoid oligomers (6- to 12-mer) were designed to adopt an amphipathic helical polyproline I-type structure. Their evaluation on a panel of bacterial strains (, , , and ), pathogenic fungi (, , and ), and human cells (hRBC, BEAS-2B, Caco-2, HaCaT, and HepG2) enabled the identification of two heptamers with improved activity to selectively fight pathogens. Modulation of parameters such as the nature of the triazolium and hydrophobic/lipophilic side chains, the charge content, and the sequence length drastically potentiates activity and selectivity.

Metabolomic profiling of COVID-19 using serum and urine samples in intensive care and medical ward cohorts.

The COVID-19 pandemic remains a significant global health threat, with uncertainties persisting regarding the factors determining whether individuals experience mild symptoms, severe conditions, or succumb to the disease. This study presents an NMR metabolomics-based approach, analysing 80 serum and urine samples from COVID-19 patients (34 intensive care patients and 46 hospitalized patients) and 32 from healthy controls. Our research identifies discriminant metabolites and clinical variables relevant to COVID-19 diagnosis and severity.

Microbiome-derived antimicrobial peptides show therapeutic activity against the critically important priority pathogen, Acinetobacter baumannii.

Acinetobacter baumannii is designated by the World Health Organisation as a critical priority pathogen. Previously we discovered antimicrobial peptides (AMPs), namely Lynronne-1, -2 and -3, with efficacy against bacterial pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa. Here we assessed Lynronne-1, -2 and -3 structure by circular dichroism and efficacy against clinical strains of A.

Synthesis of Second-Generation Analogs of Temporin-SHa Peptide Having Broad-Spectrum Antibacterial and Anticancer Effects.

Antimicrobial peptides (AMPs) are a promising class of therapeutic alternatives with broad-spectrum activity against resistant pathogens. Small AMPs like temporin-SHa () and its first-generation analog [G10a]-SHa () possess notable efficacy against Gram-positive and Gram-negative bacteria. In an effort to further improve this antimicrobial activity, second-generation analogs of were synthesised by replacing the natural glycine residue at position-10 of the parent molecule with atypical amino acids, such as D-Phenylalanine, D-Tyrosine and (2-Naphthyl)-D-alanine, to study the effect of hydrophobicity on antimicrobial efficacy.

: A Comprehensive Review of Its Phytochemical Composition and Pharmacological Activities.

(Forsskål and Niebuhr) Ascherson is a small marine seagrass that belongs to the Hydrocharitaceae family. It is native to the Red Sea, Persian Gulf, and Indian Ocean and has successfully invaded the Mediterranean and Caribbean Seas. This article summarizes the pharmacological activities and phytochemical content of , along with its botanical and ecological characteristics.

Tyrosinase Inhibition and Antimelanogenic Effects of Resorcinol-Containing Compounds.

Tyrosinases (TYRs) are copper-containing metalloenzymes present in a large diversity of species. In human, hTYR is responsible for pivotal steps in melanogenesis, catalysing the oxidation of l-tyrosine to l-DOPA and further to dopaquinone. While numerous TYR inhibitors have been reported, polyphenolic compounds tend to dominate the literature.

The Antioxidant Potential and Anticancer Activity of Ethanolic Extract against Triple-Negative Breast Cancer Cells.

Natural remedies have been indispensable to traditional medicine practices for generations, offering therapeutic solutions for various ailments. In modern times, these natural products continue to play a pivotal role in the discovery of new drugs, especially for cancer treatment. The marine ecosystem offers a wide range of plants with potential anticancer activities due to their distinct biochemical diversity and adaptation to extreme situations.

Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities.

The development of new and effective antimicrobial compounds is urgent due to the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules, but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new aurone derivatives bearing acetamido and amino groups at the position 5 of the A ring and managing various monosubstitutions at the B ring.

Interactions of Phenylalanine Derivatives with Human Tyrosinase: Lessons from Experimental and Theoretical tudies.

The pigmentation of the skin, modulated by different actors in melanogenesis, is mainly due to the melanins (protective pigments). In humans, these pigments' precursors are synthetized by an enzyme known as tyrosinase (TyH). The regulation of the enzyme activity by specific modulators (inhibitors or activators) can offer a means to fight hypo- and hyper-pigmentations responsible for medical, psychological and societal handicaps.

Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis.

Apoptosis is a programmed cell death comprising two signaling cascades including the intrinsic and extrinsic pathways. This process has been shown to be involved in the therapy response of different cancer types, making it an effective target for treating cancer. Cancer has been considered a challenging issue in global health.

Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus.

Background: Mycobacterium abscessus, a fast-growing non-tuberculous mycobacterium, is an emerging opportunistic pathogen responsible for chronic bronchopulmonary infections in people with respiratory diseases such as cystic fibrosis (CF). Due to its intrinsic polyresistance to a wide range of antibiotics, most treatments for M. abscessus pulmonary infections are poorly effective.

Design and synthesis of 4-amino-2',4'-dihydroxyindanone derivatives as potent inhibitors of tyrosinase and melanin biosynthesis in human melanoma cells.

Melanogenesis inhibition constitutes a privileged therapeutic solution to treat skin hyperpigmentation, a major dermatological concern associated with the overproduction of melanin by human tyrosinase (hsTYR). Despite the existence of many well-known TYR (tyrosinase) inhibitors commercialized in skin formulations, their hsTYR-inhibition efficacy remains poor since most of them were investigated over mushroom tyrosinase (abTYR), a model with low homology relative to hsTYR. Considering the need for new potent hsTYR inhibitors, we designed and synthesized a series of indanones starting from 4-hydroxy compound 1a, one of the two most active derivatives reported to date against the human enzyme, together with marketed thiamidol.

Gaillardin inhibits autophagy and induces apoptosis in MCF-7 breast cancer cells by regulating JAK/STAT pathway.

Background: Gaillardin is a potent anti-cancer sesquiterpene lactone found in Inula oculus-christi.

Aim: The present study examined the effects of gaillardin on apoptosis and autophagy in the MCF-7 breast cancer cell line.

Methods: The MTT assay was used to unravel the antiproliferative effects of gaillardin on MCF-7 cells.

Identification of a muropeptide precursor transporter from gut microbiota and its role in preventing intestinal inflammation.

The gut microbiota is a considerable source of biologically active compounds that can promote intestinal homeostasis and improve immune responses. Here, we used large expression libraries of cloned metagenomic DNA to identify compounds able to sustain an anti-inflammatory reaction on host cells. Starting with a screen for NF-κB activation, we have identified overlapping clones harbouring a heterodimeric ATP-binding cassette (ABC)-transporter from a Firmicutes.

The effect of a combined rehabilitation program on the temporomandibular joint in systemic sclerosis evaluated by ultrasound exam.

Purpose: Temporomandibular joint (TMJ) involvement is frequent in Systemic Sclerosis (SSc). Dysfunction and X-ray changes of TMJ were described only in few observational studies. Treatment as well has been seldom considered.

Ethnopharmacology and therapeutic potential of : a comprehensive review.

Banks and Sol. is a rough flowering plant of the Boraginaceae family native to Eastern Mediterranean region that is widely used in traditional herbal medicine, mainly for the treatment of wounds, abdominal pain, and arthritis, to name a few. This article aims to gather knowledge related to the medicinal properties of .