Search Results (146)

The increase in multidrug resistance in microorganisms and the rise of emergent infectious diseases worldwide is a threat to human and animal health. Therefore, research on new molecules with antibiotic potential is a priority. Lichens have a unique secondary metabolism with relatively untapped potential, yet their essential oils (EOs) and volatile organic compounds (VOCs) remain a relatively untapped resource. This systematic review was conducted following PRISMA 2020 guidelines, with a comprehensive search performed in the Web of Science database for studies published up to 2023. From 254 identified records, six studies involving nine lichen species (Evernia prunastri, Evernia divaricata, Cladonia rangiformis, Cladonia furcata, Parmotrema perlatum, Lichina pygmaea, Parmelia perlata, Hypogymnia physodes, and Parmelia sulcata) met the eligibility criteria. The synthesized data show that these volatile fractions possess significant antimicrobial potential, with minimum inhibitory concentrations (MICs) generally lower than 1 mg/mL. Major bioactive constituents identified include atraric acid, orsellinates, and various sesquiterpenes. While the current evidence highlights a strong potential of lichen volatiles against pathogens, research is limited to a small fraction of known species. This review identifies a critical gap in testing these compounds directly against MDR clinical isolates and suggests that future research should focus on high-biomass species and the heterologous expression of lichen biosynthetic genes to develop sustainable antimicrobial applications. Full article

Sand extraction drastically alters ecosystem structure and initiates conditions for primary succession development. Forest stands aged 9, 16, 19, and 28 years were surveyed to assess understory vegetation and epiphytic lichen communities in post-mining sand and gravel quarries in eastern Latvia. Community structure and functional traits were analyzed. Younger stands (9–19 years) exhibited the highest understory species diversity, dominated by hemicryptophytes, open-habitat grasses, and low-to-moderate ecological value lichens, while older stands (28 years) supported high-value epiphytic lichens and understory species typical of oligotrophic boreal forests. In 9-year-old stands, high-value epiphytic lichens comprised, on average, 5.7% (SE = 1.6) total lichen cover, while in 28-year-old stands it was 24.8% (SE = 1.9). Species with animal-mediated seed dispersal were more prevalent in younger stands, reflecting indications of animal presence based on vegetation composition and observed animal damage on trees. No invasive species were recorded, likely due to quarry isolation (≥1 km closest edge of the forest ecosystem) and proximity to mature forest margins. Our results highlight the multidimensionality of biodiversity by integrating two taxonomic groups and indicate high potential for passive natural regeneration toward Western Taiga 9010 habitat conditions under an oligotrophic environment. Full article

Objectives: This systematic review aimed to evaluate malignant transformation (MT) in extraoral lichen planus to help contextualize the debated malignant potential of oral lichen planus in a mucocutaneous disease model. Methods: A comprehensive literature search was conducted across five databases and gray literature sources, without date restrictions. Observational studies reporting MT in cutaneous or genital LP were included. Data extraction, risk of bias assessment using Joanna Briggs Institute (JBI), and meta-analysis of proportions were performed. Subgroup analyses by anatomical site were conducted where possible. Results: Ten studies (15,829 patients) were included, with a predominance of women (93.1%). The pooled MT rate of extraoral LP was 1% (95% CI: 0.00–0.03). Subgroup analysis revealed a significantly higher rate in vulvar LP (2%; 95% CI: 0.02–0.03) compared to cutaneous LP (0%; 95% CI: 0.00–0.01) (p < 0.0001). Squamous cell carcinoma was the most frequent malignancy. The erosive and hypertrophic subtypes of LP were more commonly associated with cancer development. Conclusions: MT of extraoral LP appears to be rare, particularly in cutaneous forms. However, the risks observed in the genital mucosa reinforce the need for accurate diagnosis and long-term follow-up, especially in erosive presentations. Full article

In this study, sixteen secondary metabolites, including two chromones, four dibenzofurans, three lipids, three depsides, two aromatic compounds, a quinone, and a terpene, were detected in the methanol:acetone (1:1 v/v) extract of the lichen Hypotrachyna enderythraea (Zahlbr.) Hale, using High-Performance Liquid Chromatography coupled to Orbitrap Electrospray Ionization tandem Mass Spectrometry (HPLC-Orbitrap ESI tandem MS/MS). These metabolites were characterized by analysis of their exact molecular masses and corresponding fragmentation patterns. The retention times of the identified metabolites were compared with those of standard compounds, confirming the presence of naturally occurring bioactive compounds. Density Functional Theory (DFT) calculations were employed to investigate preferential deprotonation sites in representative polyprotic metabolites. All these findings may contribute to expanding the spectrum of compounds identified within the genus Hypotrachyna and to evaluating their potential biological activities. Full article

Usnic acid (UA) is one of the most extensively studied specialized metabolites of lichens, attracting considerable interest due to its antimicrobial, anti-inflammatory, and cytotoxic properties. The efficiency of UA extraction from lichens depends on multiple interrelated biological and technological factors. This systematic review aims to synthesize and critically evaluate reported strategies for UA extraction from wild-grown lichen biomass, with particular emphasis on extraction efficiency, practicality, and application potential. This systematic literature review, based on the Scopus database was conducted by including original research articles reporting UA extraction from wild-growing lichens. The analysis covered species selection, sample pre-treatment, solvent type, and extraction methodology. A total of 117 studies were included. Due to the predominantly non-polar nature of UA, higher extraction efficiencies were generally achieved using solvents, including acetone, supercritical CO₂, vegetable oils, and lipophilic green solvent systems. Pre-treatment strategies such as grinding or flaking significantly enhanced extraction performance by improving mass transfer. Alongside conventional methods (maceration, reflux, Soxhlet), non-conventional techniques such as Supercritical Fluid Extraction (SFE), Ultrasound- (UAE), and Microwave-Assisted Extraction (MAE) enabled faster and more selective UA extraction with reduced solvent use. Notably, SFE have been reported as particularly promising in terms of selectivity, process control, and potential suitability for scale-up, with commercially available supercritical CO₂ extracts of Usnea species supporting the feasibility of this approach. This review provides a consolidated and application-oriented overview of UA extraction, highlighting strategies that balance efficiency, selectivity, sustainability, and practical implementation. Full article

This study presents a comparative analysis of secondary metabolites and antioxidant, antimicrobial, and anticancer activities of acetone extracts obtained from the lichens Lepraria incana and Pertusaria amara. HPLC-UV analysis identified divaric acid, divaricatinic acid, norstictic acid, divaricatic acid and usnic acid in L. incana, and conprotocetraric acid, protocetraric acid, picrolichenic acid and atranorin in P. amara. Free radical scavenging capacity and reducing power assays were employed to assess the antioxidant activity of the extracts. The IC₅₀ values in the free radical scavenging assay were 664.23 μg/mL for L. incana and 750.50 μg/mL for P. amara, while reducing power absorbances varied between 0.0875–0.2562 and 0.0336–0.2011, respectively. Total phenolic contents in L. incana and P. amara extracts were 40.81 and 33.67 μg PE/mg of extract, while total flavonoid contents were 24.74 and 23.61 μg RE/mg of extract, respectively. Antimicrobial activity, determined by the microdilution method, ranged from 156 to 20 × 10³ μg/mL for L. incana and from 312 to 20 × 10³ μg/mL for P. amara. Cytotoxicity was tested using the MTT method. Among the tested samples, the L. incana extract showed the strongest cytotoxic activity toward A549 cells, with an IC₅₀ value of 47.53 μg/mL. Based on the results, the lichens examined demonstrate promise for future studies and potential development in biopharmaceutical applications. Full article

Background/Objectives: The global rise in multidrug-resistant (MDR) bacteria, particularly methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA and MSSA), continues to pose a major public health challenge, including in Hawaii. This underscores the need to discover new antimicrobial agents from natural sources. Guided by teachings from a Buddhist master regarding the medicinal value of lichens, we investigated the endemic Hawaiian lichen Cladonia skottsbergii. Methods: Specimens of C. skottsbergii were collected from the Lotus Buddhist Monastery in Mountain View, Hawaii. A methanolic extract was prepared and purified using chromatographic techniques, and compound structures were elucidated through spectroscopic analyses and single-crystal X-ray diffraction. The antibacterial activity of the compounds was assessed against Gram-positive strains (MRSA, MSSA) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa). Cytotoxicity was assessed using A549 (non-small cell lung cancer) and Vero E6 (non-tumorigenic) cell lines. Results: Three compounds were isolated: clarosione (1), a newly identified trichlorinated xanthone, and two known metabolites, (S)-usnic acid (2) and perlatolic acid (3). Compounds 2 and 3 demonstrated strong inhibitory effects against MRSA and MSSA. Their minimum inhibitory concentrations (MICs) ranged from 2 to 4 µg/mL, compared with vancomycin (0.5–1 µg/mL). Cytotoxicity testing showed higher sensitivity in A549 cells than in Vero E6 cells, resulting in favorable selectivity indices for the active compounds. Conclusions: In the current study, a new compound, clarosione (1) was discovered. This enhances our understanding of the constituents of C. skottsbergii and its potential antibacterial properties. Lichen-derived compounds may serve as lead candidates for further development, and further study is warranted. Full article

Background/Objective: To comprehensively characterize the genetic landscape of medullary thyroid carcinoma (MTC) in a Romanian cohort. Methods: Germline and somatic RET testing were performed in 164 MTC patients (105 sporadic, 59 hereditary) consecutively enrolled at a single tertiary center (2021–2024) using genomic DNA or DNA extracted from fresh surgical or paraffin-embedded pathology specimens. Results: Hereditary MTC (hMTC) accounted for 59/164 (35.9%) cases. Among hMTC, 58/59 (98.3%) had MEN2 (72.4% classic, 5.2% with cutaneous lichen amyloidosis, 5.2% with Hirschsprung disease, and 17.2% with familial medullary thyroid carcinoma), and 1/59 (1.7%) had MEN3. Codon 634 mutations were the most prevalent (33/59, 55.9%). Extracellular cysteine-rich domain mutations were significantly more prevalent in syndromic cases (p = 0.006), while non-cysteine mutations were predominant in apparently sporadic cases (p = 0.006). In advanced MTC (stage III/IV or metastatic), the somatic M918T mutation was the most common (15/20, 75% cases). Conclusions: Germline RET screening is mandatory for all MTC cases. Somatic testing is critical in advanced disease, where M918T prevails in 75% of cases and guides tyrosine kinase inhibitor therapy. Codon 634 is the most frequent mutation in Romanian MTC, highlighting regional variation warranting population-adjusted screening and earlier prophylactic thyroidectomy. Full article

Lichens are a source of diverse compounds with a wide range of biological activities, making them of significant interest for novel drug development. In this study, metabolites were extracted from Lobariaceae lichens, and their antioxidant and antibacterial properties were experimentally investigated and explained using various computational approaches. Specifically, four lichen metabolites were analyzed using three methods to assess their antioxidant capacity. Antibacterial activity assays were conducted against four pathogens, and the minimum inhibitory concentrations (MICs) of the most promising compounds were determined. Ab initio studies were performed to evaluate radical stability. A pharmacological target responsible for the antibacterial effect was identified, and possible binding sites and modes were studied in silico. Metabolite IX, physciosporin, exhibited the highest antioxidant activity, which was associated with the theoretical stability of the radical. Additionally, IX exhibited an MIC of 0.97 μg/mL against S. pyogenes, surpassing the potency of streptomycin. The RecA protein was identified as a potential target, and a possible binding site and pattern of interactions at that site were described. Finally, IX showed low cytotoxicity in human cancer cell lines and was predicted to have favorable oral absorption properties, supporting its potential as a promising antioxidant and antibacterial agent against S. pyogenes. Full article

Lichens are complex symbiotic systems known for synthesizing diverse secondary metabolites with documented antimicrobial, antioxidant, and antiproliferative activities. The present study focused on Pseudevernia furfuracea, a species widely distributed across Moroccan habitats. Two hydrodistillation-derived extracts (HE1 and HE2) were analyzed through ultra-high-Performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) to characterize their metabolite composition, and their effects were evaluated on Jurkat cells, a representative human cell line of the immune system. As the results of the characterization, the main compounds identified were Caprolactam, N,N-Diethylaniline, Erucamide, and 4-Isopropylaniline. Cytotoxicity assessment revealed that both HE1 and HE2 decreased the viability of Jurkat cells in a concentration-dependent manner. The mean effective concentrations (EC₅₀) after 24 h of treatment were 53.79 ± 2.92 µg/mL for HE1 and 59.76 ± 2.01 µg/mL for HE2. Cell death mechanisms were further examined by flow cytometry, revealing that apoptosis predominated after 24 h of treatment, progressing mainly to late apoptotic stages after 48 h. In parallel, the expression levels of key cytokine genes, including IL-2, TNF-α, and IFN-γ, were quantified at the mRNA level to evaluate potential immunomodulatory effects. Up-regulation was observed in IL-2 after exposure to both extracts for 24 and 48 h, and in the case of IFN-γ after exposure to HE2 for 24 h; in contrast, HE1 and HE2 produced down-regulation in TNF-α at 24 h. These findings suggest that HE1 and HE2 have immunomodulatory activity in Jurkat cells. Further investigations are needed to elucidate the underlying mechanisms and to clarify how HE1 and HE2 influence immune responses in human systems. Full article

The cannabidiol (CBD)-rich cannabis extract CAN296 shows anti-inflammatory and anticancer activity relevant to oral lichen planus (OLP), oral graft-versus-host disease (oGVHD), and oral squamous cell carcinoma (OSCC), but its high lipophilicity limits aqueous dispersion. This study developed a stable Tween-based nanoemulsion optimized for oral mucosal delivery. Ethanol-dissolved CAN296 was nanoemulsified using a 1% Tween/Span system. Physical stability was visually assessed; droplet size and morphology were examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM); and wettability was measured by static contact angle (SCA). Additional evaluations included temperature stability (25 °C vs. 4 °C), in vitro release using a dialysis membrane, and scanning electron microscopy (SEM) of membrane-associated droplets. Nanoemulsions with ≥80% Tween 80 incorporated CAN296 up to 800 µg/mL, clear at 400 µg/mL, and uniformly turbid at 800 µg/mL. DLS and TEM confirmed spherical nanoscale droplets, and SCA indicated favorable cohesion and wettability. Stability was maintained for 30 days at 4 °C. Dialysis studies demonstrated strong membrane association with limited diffusion, supported by SEM visualization of membrane-bound droplets. The Tween-dominant (≥80%) nanoemulsion stably incorporated CAN296 up to 800 µg/mL, demonstrated nanoscale uniformity, improved 4 °C stability, and strong membrane retention under static conditions, suggesting potential for localized oral delivery. Full article

The lipid composition of the mycobint and photobiont symbiotic partners of lichenized ascomycetes varies greatly. The aim of this study was to compare the profile of the major sterols in two closely related lichens from the genus Lobaria with different photobionts. The three-component lichen Lobaria pulmonaria has two photobionts. While the main photobiont is the chlorophycean alga Symbiochloris reticulata, this lichen contains small amounts of the cyanobacterium Nostoc. By contrast, the cyanobacterium Nostoc is the main photobiont in Lobaria retigera. Relatively loosely bound sterols were extracted using a chloroform–methanol mixture, and subsequently, more tightly bound sterols by alkaline saponification. The initial chloroform–methanol extraction step indicated that ergosterol is the principal sterol in both species, with phytosterols constituting a minor fraction. However, the addition of an alkaline saponification step to the standard protocol of sterol extraction greatly increases the release of tightly bound phytosterols, such as campesterol, stigmasterol, and β-sitosterol from L. pulmonaria, but not from L. retigera. Therefore, the mycobionts and Nostoc mainly possess sterols extractable by the standard mixture of chloroform/methanol, while the chlorophycean algal photobiont contains tightly bound sterols. This observation could be important when studying the roles of sterols in the stress tolerance of lichens. Full article

This study investigates the immunomodulatory effects of a well-characterized cannabidiol (CBD)-rich cannabis extract, CAN296, on T lymphocytes (T cells), particularly Cluster of Differentiation 4 (CD4⁺) helper and Cluster of Differentiation 8 (CD8⁺) cytotoxic subsets, by examining T-cell activation, cytokine secretion, and cytotoxic molecule expression in comparison with the conventional treatments dexamethasone (DEX) and tacrolimus (TAC). It addresses key processes involved in the formation of premalignant immune-mediated lesions, such as those seen in oral lichen planus (OLP) and oral manifestations of graft-versus-host disease (oGVHD). CD4⁺ and CD8⁺ T cells were isolated from healthy donors and assessed in vitro for T cell activation via CD69 expression, secreted tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels according to enzyme-linked immunosorbent assay (ELISA), and cytotoxic molecule expression Granzyme B, Perforin, Fas Ligand (Fas-L) quantified by flow cytometry. Cells were treated with different doses of CAN296 (2, 4, 8 µg/mL), DEX (0.4, 4, 40 µg/mL), or TAC (0.1, 1, 10 ng/mL), and all parameters were compared to untreated controls. CAN296 significantly inhibited T cell activation, reducing CD69 expression in CD4⁺ T cells to 2–11% and in CD8⁺ T cells to 5–17%. It also markedly suppressed TNF-α secretion in CD4⁺ T cells at all concentrations (p < 0.0001). In CD8⁺ T cells, CAN296 led to a near-complete reduction in TNF-α and IFN-γ, leaving both cytokines barely detectable at all tested doses (p < 0.0001). The effect of cell inhibition was significantly more pronounced than that observed with DEX or TAC, displaying dose-dependent reductions. TAC inconsistently lowered TNF-α while paradoxically increasing IFN-γ at lower concentrations. Additionally, CAN296 consistently suppressed cytotoxic molecule expression, reducing Granzyme B by 81–82%, Perforin by 40–53%, and Fas-L by 40–44%. DEX showed variable effects on cytotoxic molecule expression. At the same time, TAC demonstrated inconsistent modulation of Perforin and Granzyme B. Overall, CAN296 outperformed DEX and TAC, demonstrating more potent and consistent immunomodulatory effects. CBD-rich cannabis extract, CAN296, exhibits potent immunomodulatory properties by effectively inhibiting T cell activation, lowering pro-inflammatory cytokines, and suppressing cytotoxic molecule expression. Its efficacy surpasses conventional therapies like DEX and TAC, offering a promising novel treatment modality for T cell-mediated disorders, including OLP and oGVHD. These findings support further development of CAN296 formulations to optimize dosing and delivery, followed by clinical trials to validate its therapeutic potential. Full article