Foodborne diseases triggered by various infectious micro-organisms are contributing significantly to the global disease burden as well as to increasing mortality rates. Salmonella enterica belongs to the most prevalent form of bacteria accountable for significant burden of foodborne illness across the globe. The conventional therapeutic approach to cater to Salmonella enterica-based infections relies on antibiotic therapy, but the rapid emergence of the antibiotic resistance strains of Salmonella sp. necessitates the development of alternative treatment and prevention strategies. In light of this growing concern, the scientific community is rigorously exploring novel phytochemicals harnessed from medicinally important plants as a promising approach to curb Salmonella enterica infections. A variety of phytochemicals belonging to alkaloids, phenols, flavonoid, and terpene classes are reported to exhibit their inhibitory activity against bacterial cell communication, membrane proteins, efflux pumps, and biofilm formation among drug resistant Salmonella strains. The present review article delves to discuss the emergence of antibiotic resistance among Salmonella enterica strains, various plant sources, identification of phytochemicals, and the current state of research on the use of phytochemicals as antimicrobial agents against Salmonella enterica, shedding light on the promising potential of phytochemicals in the fight against this pathogen.

• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• Drug Resistance, Bacterial MeSH
• Phytochemicals * pharmacology   chemistry   MeSH
• Humans MeSH
• Foodborne Diseases microbiology   prevention & control   drug therapy   MeSH
• Salmonella enterica * drug effects   MeSH
• Salmonella Infections * microbiology   drug therapy   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

One of the main challenges in analyzing chemical messengers in the brain is the optimization of tissue sampling and preparation protocols. Limiting postmortem time and terminating enzyme activity is critical to identify low-abundance neurotransmitters and neuropeptides. Here, we used a rapid and uniform conductive heat transfer stabilization method that was compared with a conventional fresh freezing protocol. Together with a selective chemical derivatization method and an optimized quantitation approach using deuterated internal standards, we spatially mapped neurotransmitters and their related metabolites by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in rat brain tissue sections. Although the heat stabilization did not show differences in the levels of dopamine, norepinephrine, and serotonin, their related metabolites 3,4-dihydroxyphenylacetaldehyde, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylacetaldehyde, dihydroxyphenylethyleneglycol, and 5-hydroxyindoleacetic acid were all significantly lower, indicating reduced neurotransmitter postmortem turnover ratios. Heat stabilization enabled detection of an increased number and higher levels of prodynorphin, proenkephalin, and tachykinin-derived bioactive neuropeptides. The low-abundant C-terminal flanking peptide, neuropeptide-γ, and nociceptin remained intact and were exclusively imaged in heat-stabilized brains. Without heat stabilization, degradation fragments of full-length peptides occurred in the fresh frozen tissues. The sample preparation protocols were furthermore tested on rat brains affected by acute anesthesia induced by isoflurane and medetomidine, showing comparable results to non-anesthetized animals on the neurotransmitters level without significant changes. Our data provide evidence for the potential use of heat stabilization prior to MALDI-MSI analyses to improve the examination of the in vivo state of neuronal chemical messengers in brain tissues not impacted by prior acute anesthesia.

• MeSH
• Rats MeSH
• Brain Chemistry * physiology   MeSH
• Brain * metabolism   MeSH
• Neurons * metabolism   chemistry   MeSH
• Neurotransmitter Agents * metabolism   analysis   MeSH
• Rats, Sprague-Dawley MeSH
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization * methods   MeSH
• Hot Temperature * MeSH
• Freezing MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Rare and unknown actinobacteria from unexplored environments have the potential to produce new bioactive molecules. This study aimed to use 16 s rRNA metabarcoding to determine the composition of the actinobacterial community, particularly focusing on rare and undescribed species, in a nature reserve within the Brazilian Cerrado called Sete Cidades National Park. Since this is an inaccessible area without due legal authorization, it is understudied, and, therefore, its diversity and biotechnological potential are not yet fully understood, and it may harbor species with groundbreaking genetic potential. In total, 543 operational taxonomic units (OTUs) across 14 phyla were detected, with Actinobacteria (41.2%), Proteobacteria (26.5%), and Acidobacteria (14.3%) being the most abundant. Within Actinobacteria, 107 OTUs were found, primarily from the families Mycobacteriaceae, Pseudonocardiaceae, and Streptomycetaceae. Mycobacterium and Streptomyces were the predominant genera across all samples. Seventeen rare OTUs with relative abundance < 0.1% were identified, with 82.3% found in only one sample yet 25.5% detected in all units. Notable rare and transient genera included Salinibacterium, Nocardia, Actinomycetospora_01, Saccharopolyspora, Sporichthya, and Nonomuraea. The high diversity and distribution of Actinobacteria OTUs indicate the area's potential for discovering new rare species. Intensified prospection on underexplored environments and characterization of their actinobacterial diversity could lead to the discovery of new species capable of generating innovative natural products.

• MeSH
• Actinobacteria * chemistry   classification   genetics   isolation & purification   MeSH
• Biodiversity MeSH
• Metagenome MeSH
• Soil chemistry   MeSH
• Soil Microbiology * MeSH
• RNA, Ribosomal, 16S analysis   MeSH
• DNA Barcoding, Taxonomic MeSH
• Parks, Recreational MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Brazil MeSH

Current antibiotics and chemotherapeutics are becoming ineffective because pathogenic bacteria and tumor cells have developed multiple drug resistance. Therefore, it is necessary to find new substances that can be used in treatment, either alone or as sensitizing molecules in combination with existing drugs. Peptaibols are bioactive, membrane-active peptides of non-ribosomal origin, mainly produced by filamentous fungi such as Trichoderma spp. This study focused on producing peptaibol-rich extracts from Trichoderma atroviride O1, cultivated on malt extract agar (MA) under circadian and constant darkness conditions for 13 days. Peptaibol production was detected by MALDI-TOF mass spectrometry after six days of cultivation. The extracts demonstrated antibacterial activity against Staphylococcus aureus strains, particularly the methicillin-resistant variant, but not against the Gram-negative Pseudomonas aeruginosa. Quorum sensing interference revealed that a peptaibol-rich extract suppressed Vibrio campbellii BAA-1119's AI-2 signaling system to a degree comparable with gentamycin. Beyond antibacterial properties, the extracts exhibited notable antiproliferative activity against human ovarian cancer cells and their adriamycin-resistant subline in both 2D and 3D models. Specifically, MA-derived extracts reduced ovarian cancer cell viability by 70% at 50 μg/mL, especially under light/dark regime of cultivation. Compared to previously published results for PDA-based extracts, MA cultivation shifted the biological effects of peptaibol-containing extracts toward anticancer potential. These findings support the idea that modifying fungal cultivation parameters, the bioactivity of secondary metabolite mixtures can be tailored for specific therapeutic applications.

• MeSH
• Agar * chemistry   MeSH
• Anti-Bacterial Agents * pharmacology   metabolism   MeSH
• Hypocreales MeSH
• Culture Media chemistry   MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Cell Line, Tumor MeSH
• Peptaibols * pharmacology   metabolism   biosynthesis   chemistry   MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Agents * pharmacology   metabolism   MeSH
• Pseudomonas aeruginosa drug effects   MeSH
• Staphylococcus aureus drug effects   MeSH
• Trichoderma * metabolism   growth & development   chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Food hydrocolloids, derived from natural sources such as plants, algae, and microbes, possess bioactive properties that significantly contribute to cardiovascular health. This review focuses on six key hydrocolloids: alginate, astragalus polysaccharides, carrageenan, fucoidan, lunasin, and psyllium, while also considering other important natural hydrocoloids such as short chain fatty acids (SCFAs), plant-derived food hydrocolloids, plant-derived gums, plant-derived mucilages, pectin, modified citrus pectin, inulin, naringenin, chia seeds, gelatine, whey protein, casein, microbial exopolysaccharides and gums, ulvan, and laminarin. Alginate, from brown seaweed, aids in cardiac tissue regeneration and repair. Astragalus polysaccharides, from the Astragalus plant, provide antioxidant, anti-inflammatory, and immunomodulatory benefits. Carrageenan, sourced from red seaweed, supports lipid profile balance and heart health. Fucoidan, another brown seaweed derivative, offers antihypertensive and lipid-lowering effects. Lunasin, a peptide found in soybeans, oats, and barley, is known for its cholesterol-lowering properties and anti-inflammatory effects. Psyllium, rich in soluble fiber, helps lower LDL cholesterol and improve overall cardiovascular function. These hydrocolloids, along with other mentioned compounds, are utilized in drug formulations, cosmetics, processed foods, and dietary supplements, enhancing food texture and stability while delivering health benefits. Upon consumption, they can be absorbed into the bloodstream or metabolized by gut microbiota into bioactive metabolites. This review examines their effects on cardiovascular function, highlighting their mechanisms in regulating vascular tone, blood pressure, vascular inflammation, and cardiac function. It consolidates current research, emphasizing the potential of these hydrocolloids and related compounds in the prevention and management of cardiovascular diseases (CVDs).

• MeSH
• Alginates * chemistry   pharmacology   MeSH
• Carrageenan * chemistry   pharmacology   MeSH
• Cardiovascular Diseases * prevention & control   MeSH
• Cardiovascular System * drug effects   MeSH
• Colloids chemistry   pharmacology   MeSH
• Humans MeSH
• Polysaccharides * chemistry   pharmacology   MeSH
• Psyllium * chemistry   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

To address the challenge of drug accumulation and penetration at the tumor site(s), herein we describe a first-in-class nanocarrier containing 24 copies each of two bioactive peptides (BAPs) genetically fused in frame to the 24 N-termini of a human ferritin H-type construct, named THE-10. The two BAPs are specific for PD-L1 and integrin αVβ3/αVβ5 plus Neuropilin (iRGD) respectively, conferring immune checkpoint blockade and drug-internalization properties. In turn, the THE-10 backbone brings 48 BAPs contiguous for synergism, prolonged blood half-life, and release into the tumor microenvironment upon conditional cleavage of a metalloprotease-sensitive site. Predicted THE-10 multitasking activity was experimentally supported as follows. Size-exclusion chromatography and surface plasmon resonance demonstrated BAP cleavage/release and receptor binding (nanomolar KD). Live-cell/time-lapse imaging demonstrated 4-fold-increased internalization of naked therapeutic antibodies, mirrored by enhanced cytotoxicity of the corresponding Antibody-Drug Conjugate. Slight antitumor effects were observed in vivo by treating immune checkpoint-sensitive syngeneic mouse colorectal model with THE-10 alone. Drug boosting was instead considerable on colorectal and pancreatic tumor allografts when THE-10 was co-administered with both small and large chemotherapeutic agents, outperforming the original iRGD cyclic peptide. Thus, THE-10 may enhance target therapy, chemotherapy and immunotherapy altogether, e.g. it candidates as a multitasking, all-round, antineoplastic therapy booster.

• MeSH
• Ferritins * chemistry   genetics   pharmacology   MeSH
• Immunotherapy * MeSH
• Humans MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Nanoparticles * chemistry   MeSH
• Drug Carriers * chemistry   MeSH
• Antineoplastic Agents pharmacology   chemistry   MeSH
• Recombinant Proteins chemistry   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The objective of our in vitro study was to quantify the biochemical profile where the total polyphenol, flavonoid and phenolic acid content was determined. The antioxidant potential of microgreen extract from Trigonella foenum-graecum L., was measured molybdenum reducing power assay. Specifically, the study assessed parameters such as metabolic activity (AlamarBlueTM assay), membrane integrity (CFDA-AM assay), mitochondrial potential (JC-1 assay), as well as reactive oxygen species generation (NBT assay). In addition, the steroid hormone release in TM3 murine Leydig cells after 12 h and 24 h exposures were quantified by enzyme-linked immunosorbent assay. The gained results indicate the highest value in total flavonoid content (182.59+/-2.13 mg QE) determination, supported by a significant (108.25+/-1.27 mg TE) antioxidant activity. The effects on metabolic activity, cell membrane integrity, and mitochondrial membrane potential were found to be both time- and dose-dependent. Notably, a significant suppression in reactive oxygen species generation was confirmed at 150, 200 and 250 microg/ml after 24 h exposure. In addition, progesterone and testosterone release was stimulated up to 250 microg/ml dose of Trigonella, followed by a decline in both steroid production at 300 and 1000 microg/ml. Our results indicate, that Trigonella at lower experimental doses (up to 250 microg/ml) may positively affect majority of monitored cell parameters in TM3 Leydig cells. Overleaf, increasing experimental doses may negatively affect the intracellular parameters already after 12 h of in vitro exposure. Key words Microgreens, Trigonella foenum-graecum L., Fenugreek, Leydig cells, Male reproduction.

• MeSH
• Antioxidants pharmacology   MeSH
• Cell Line MeSH
• Phytochemicals pharmacology   MeSH
• Leydig Cells * drug effects   metabolism   MeSH
• Membrane Potential, Mitochondrial drug effects   MeSH
• Mice MeSH
• Reactive Oxygen Species metabolism   MeSH
• Plant Extracts * pharmacology   MeSH
• Testosterone metabolism   MeSH
• Trigonella * chemistry   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. The manifestation of MS is related to steroid changes during the menstrual cycle and pregnancy. As data focusing on the effect of anti-MS drug treatment on steroidome are scarce, we evaluated steroidomic changes (79 steroids) in 61 female MS patients of reproductive age 39 (29, 47) years (median with quartiles) after treatment with anti-MS drugs on the GC-MS/MS platform and immunoassays (cortisol and estradiol). The changes were assessed using steroid levels and steroid molar ratios (SMRs) that may reflect the activities of steroidogenic enzymes (SMRs). A repeated measures ANOVA, followed by multiple comparisons and OPLS models, were used for statistical analyses. The anti-MS treatment decreased steroid levels in the follicular phase. Anti-CD20 monoclonal antibodies (mAb), such as ofatumumab and ocrelizumab; inhibitors of the sphingosine-1-phosphate receptor (S1PRI); and IFNβ-1a decreased circulating 17-hydroxy-pregnanes and shifted the CYP17A1 functioning from the hydroxylase- toward the lyase step. Decreased conjugated/unconjugated steroid ratios were found after treatment with anti-MS drugs, especially for glatiramer acetate and anti-CD20 mAb. In the luteal phase, IFN-β1a treatment increased steroidogenesis; both IFN-β1a and ocrelizumab increased AKR1D1, and S1PRI increased SRD5A functioning. Anti-CD20 mAb reduced the functioning of enzymes catalyzing the synthesis of immunomodulatory 7α/β and 16α-hydroxy-androgens, which may affect the severity of MS. The above findings may be important concerning the alterations in bioactive steroids, such as cortisol; active androgens and estrogens; and neuroactive, neuroprotective, and immunomodulatory steroids in terms of optimization of anti-MS treatment.

• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Multiple Sclerosis * drug therapy   metabolism   MeSH
• Steroids therapeutic use   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Skin represents the largest organ in the human body, functioning as a protective barrier against environmental factors while playing a critical role in thermoregulation. Acne vulgaris is recognized as the most common dermatological condition affecting adolescents, and if left untreated, it can result in lasting skin damage and associated psychosocial challenges. This study aims to develop innovative polymeric biomaterials that could effectively support the treatment of acne vulgaris. The synthesis of these biomaterials involves the use of polyethylene glycol 6000, sodium alginate, and the antioxidant protein glutathione (GHS) to create polymeric hydrogels. These hydrogels were generated via a UV-mediated crosslinking process. To enhance the functional properties of the hydrogels, zinc oxide microparticles (ZnO), synthesized through a wet precipitation method, were incorporated into the formulations. Characterization of the ZnO was performed using Fourier-Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), particle sizer analysis, and Scanning Electron Microscopy (SEM). Additionally, the bioactivity of the synthesized materials was evaluated through incubation in media simulating physiological body fluids. The cytotoxic effects of the biomaterials were assessed using an indirect test on mouse fibroblast (L929) cells, in accordance with ISO 10993-5 guidelines. The results of our research indicate that the developed biomaterials exhibit potential as a carrier for active substances, contributing positively to the treatment of acne vulgaris and potentially improving overall skin health.

• MeSH
• Acne Vulgaris drug therapy   MeSH
• Alginates chemistry   MeSH
• Biocompatible Materials chemistry   pharmacology   MeSH
• Cell Line MeSH
• Fibroblasts drug effects   metabolism   MeSH
• Glutathione * metabolism   MeSH
• Hydrogels * chemistry   MeSH
• Skin * drug effects   metabolism   MeSH
• Humans MeSH
• Mice MeSH
• Drug Carriers chemistry   MeSH
• Zinc Oxide * chemistry   pharmacology   MeSH
• Regeneration drug effects   MeSH
• Spectroscopy, Fourier Transform Infrared MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Platinum(IV) compounds possess distinct properties that set them apart from platinum(II) compounds. Often designed as prodrugs, they are reduced within cancer cells to their active platinum(II) form, enabling their cytotoxic effects. Their versatility also lies in their ability to be functionalized and conjugated with bioactive molecules to enhance cancer cell targeting. This report introduces new prodrugs that combine antitumor cisplatin with axially coordinated eugenol, leveraging their synergistic action to target cancer stem cells. A third bioactive ligand, 4-phenylbutyrate or octanoate, was added to further enhance biological activity, creating 'triple action' prodrugs. These new platinum(IV) prodrugs offer a novel approach to cancer therapy by improving targeting, increasing efficacy, overcoming drug resistance, and reducing tumor invasiveness while sparing healthy tissue.

• MeSH
• Cisplatin * pharmacology   MeSH
• Eugenol * pharmacology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Neoplastic Stem Cells * drug effects   pathology   MeSH
• Colonic Neoplasms * drug therapy   pathology   MeSH
• Prodrugs * pharmacology   chemistry   MeSH
• Antineoplastic Agents * pharmacology   chemistry   MeSH
• Drug Synergism MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH