Low Cytotoxicity Research Articles

Biocompatibility of light responsive materials prepared for accommodative intraocular lenses manufacturing.

To investigate the biocompatibility and bacterial adhesion properties of light responsive materials (LRM) and analyze the feasibility and biosafety of employing LRM in the preparation of accommodative intraocular lenses (AIOLs). Employing fundamental experimental research techniques, LRM with human lens epithelial cells (hLECs) and human retinal pigment epithelium cells (ARPE-19 cells) were co-cultured. Commercially available intraocular lenses (IOLs) were used as controls to perform cell counting kit-8 (CCK-8), cell staining under varying light intensities, cell adhesion and bacterial adhesion experiments. LRM exhibited a stronger inhibitory effect on the proliferation of ARPE19 cells than commercially available IOLs when co-cultured with the undiluted extract for 96h (P<0.05). Under other culturing conditions, the effects on the proliferation of hLECs and ARPE-19 cells were not significantly different between the two materials. Under the influence of light irradiation at intensities of 200 and 300 mW/cm2, LRM demonstrated a markedly higher inhibitory effect on the survival of hLECs compared to commercially available IOLs (P<0.0001). They also showed a stronger suppressive effect on the survival rate of ARPE-19 cells, with significant differences observed at 200 mW/cm2 (P<0.001) and extremely significant differences at 300 mW/cm2 (P<0.0001). Additionally, compared to commercially available IOLs, LRM had a higher number of cells adhering to their surface (P<0.05), as well as a significantly greater number of adherent bacterium (P<0.0001). LRM, characterized by their excellent non-contact tunable deformability and low cytotoxicity to ocular tissues, show considerable potential for use in the fabrication of AIOLs. These materials demonstrate strong cell adhesion; however, during photothermal conversion processes involving shape deformation under various light intensities, the resultant temperature rise may harm surrounding cells. These factors suggest that while the material plays a positive role in reducing the incidence of posterior capsule opacification (PCO), it also poses potential risks for retinal damage. Additionally, the strong bacterial adhesion of these materials indicates an increased risk of endophthalmitis.

Therapeutic potential of Indonesian plant extracts in combating malaria and protozoan neglected tropical disease

BackgroundNeglected tropical diseases (NTDs) afflict nearly 2 billion people worldwide and are caused by various pathogens, such as bacteria, protozoa, and trypanosoma, prevalent in tropical and subtropical regions. Among the 17 NTDs recognized by the World Health Organization (WHO), protozoal infections caused by Plasmodium, Entamoeba, Leishmania, and Trypanosoma are particularly prominent and pose significant public health. Indonesia, endowed with a rich biodiversity owing to its tropical climate, harbors numerous plant species with potent biological activities that hold promise for therapeutic interventions. Hence, efforts have been directed towards exploring Indonesian plant extracts and isolated compounds for their potential in combating protozoal diseases.MethodsThis study evaluated the antiprotozoal properties of 48 plant extracts sourced from the Cratoxylum, Diospyros, and Artocarpus genera. These extracts were screened using cell-based assays against Plasmodium falciparum (Pf), Entamoeba histolytica (Eh), Leishmania donovani (Ld), Trypanosoma brucei rhodesiense (Tbr), and Trypanosoma cruzi (Tc).ResultsExtracts derived from the roots of Cratoxylum arborescens, obtained through dichloromethane extraction, exhibited significant activity against protozoa, with an IC50 value ranging from 0.1 to 8.2 µg/mL. Furthermore, cochinchinone C was identified as an active compound capable of inhibiting the growth of Pf, Eh, Ld, and Tbr, Tc trypomastigote, and Tc epimastigote with IC50 values of 5.8 µM, 6.1 µM, 0.2 µM, 0.1 µM, 0.7 µM, and 0.07 µM, respectively. Cochinchinone C is the first compound reported to exhibit activity against protozoal neglected tropical diseases, showing low cytotoxicity with a selectivity index greater than 10 when tested against carcinoma and normal cell lines. This suggests indicating its potential as a candidate for further drug development. This is the first report of cochinchinone C’s activity against these protozoans.ConclusionThese findings establish cochinchinone C as a strong candidate for antiprotozoal drug development, highlighting the untapped therapeutic potential of Indonesia’s rich plant biodiversity.

Is Silver a Precious Metal for G-Quadruplex Stabilization Mediated by Porphyrins?

Cancer is a leading cause of death, so continuous efforts into cancer therapy are imperative. In tumor cells, telomerase and oncogene activity are key points for uncontrolled cell growth. Targeting these processes with ligands that inhibit telomerase and/or reduce oncogene expression has been identified as a promising cancer therapy. This study evaluated the selectivity and affinity of the silverII complex of 5,10,15,20-tetrakis(N-methyl-4-pyridinium)porphyrin (AgTMPyP) to stabilize DNA sequences capable of forming G4 structures mimicking the telomeric and oncogene regions, using spectroscopic, biochemical methods and in vitro assays. The tetracationic silver complex was compared with the free base, H2TMPyP, and the zincII complex, ZnTMPyP. The results obtained from UV-Vis and fluorescence methods pointed to a great affinity and good selectivity of AgTMPyP to G4 structures, especially for the oncogene MYC. In general, an increase in the ability of the studied ligands for 1O2 generation when interacting with oncogenic and telomeric G4 sequences was found. The results of the PCR stop assays proved that AgTMPyP has the ability to inhibit Taq polymerase. Additionally, in vitro assays demonstrated that the silverII complex exhibits low cytotoxicity against HaCaT— an immortalized, non-tumorigenic, skin keratinocytes cell line—and, although nonexclusive, AgTMPyP shows nuclear co-localization.

Natural Deep Eutectic Solvents (NADES) Research Framework: Bibliometric Analysis

Aims: The Natural Deep Eutectic Solvents (NADES) method is an extraction method currently being developed using affordable green solvents with low cytotoxicity. This research aims to (a) identify developments in NADES research, and (b) develop research gaps for NADES for future research. Study Design: This research was conducted using bibliometric analysis. Place and Duration of Study: Library sources refer to research articles available online that can be accessed via websites or search engines by entering specific keywords related to the topic. Methodology: A research approach using quantitative methods was carried out using bibliometric analysis. Data analysis using bibliometric analysis of “Natural Deep Eutectic Solvents” sourced by article tittle, abstract, and keywords that produced 1,045 Scopus documents. Results: The results show a growing research trend in NADES, but there are still several gaps that need to be addressed as mentioned in the proposed research framework. Conclusion: Future research should focus on more comprehensive comparisons, more detailed method explanations, deeper understanding of molecular mechanisms, and long-term stability evaluations to improve the applicability of NADES in various fields. This paper contributes to the development of NADES.

Investigating the C2 modulation of the imidazo[1,2-a]pyrazine-based hit compound CTN1122: synthesis, in vitro antileishmanial activity, cytotoxicity and casein kinase 1 inhibition.

Our research group previously discovered CTN1122, an imidazo[1,2-a]pyrazine compound with promising antileishmanial activity against intramacrophage amastigotes of Leishmania major and L. donovani strains. CTN1122 effectively targets Leishmania casein kinase 1 (L-CK1.2) and exhibits a favorable safety profile. To further explore its chemical space, we developed a convergent strategy to modify the C2 position of the imidazo[1,2-a]pyrazine core using Suzuki-Miyaura coupling of the corresponding triflate intermediate. Among 15 newly synthesized analogs, seven derivatives featuring variously substituted phenyl rings at C2 demonstrated L-CK1.2 inhibition within micromolar to submicromolar ranges and antileishmanial activity in vitro with low cytotoxicity in macrophages. Compounds 7d and 7l were particularly potent, with IC50 values of 1.25 µM and 0.92 µM against L. major, and 1.44 µM and 2.34 µM against L. donovani, respectively. They showed IC50 L-CK1.2 = 0.3 μM and 0.57 µM with enhanced selectivity indices (SI = 3.8 and 1.6) over the human CK1ε ortholog. Additionally, four C2 analogs and two C5 isomers exhibited notable antiparasitic effects without strongly inhibiting L-CK1.2, indicating a possible alternative mechanism of action. Compound 7k displayed the highest general activity, with IC50 values of 0.31 µM on L. major and 0.27 µM on L. donovani, coupled with favorable selectivity indexes.

Lung dECM matrikine-based hydrogel reverses bleomycin-induced pulmonary fibrosis by suppressing M2 macrophage polarization.

Recent studies have shown promising results using decellularized extracellular matrix (dECM) matrikines-based hydrogel as attractive strategies for preventing and alleviating fibrosis.&#xD;Methods & Results: Porcine lung decellularization and pepsin digestion were used to prepare the lung dECM hydrogel. Proteomic analysis revealed that the lung dECM hydrogel was enriched in glycoproteins, collagens, laminins, fibrinogen, held receptors, and bound growth factors. With porous structures and good mechanical properties and stability, the lung dECM hydrogel showed low cytotoxicity and good biocompatibility both in vitro and in vivo. The lung dECM hydrogel was further administered to verify the safety and effectiveness of reversing pulmonary fibrosis in a bleomycin induced rat model. The results revealed a relatively complete alveolar structure with less inflammatory infiltration and a reduced amount of collagen fiber deposition. TMT quantification proteomic analyses revealed significant downregulation of proteins, pathways, and interactions involved in the regulation of ECM components, tissue remodeling, inflammation, and the cytoskeleton and indicated that fibrosis-related proteins were obviously downregulated and inflammation-related proteins were significantly changed, particularly in macrophages, after administration of the lung dECM hydrogel. Multiplex immunohistochemical (mIHC) staining of lung tissue revealed that the inflammatory response was regulated by the lung dECM hydrogel, as indicated by a decrease in the number of CD3+ T cells and macrophages and the suppression of M2 macrophage polarization. Gene set enrichment analysis revealed that downregulated ficolin signaling was enriched in macrophages after lung dECM hydrogel administration, and the findings were verified in lung tissue by mIHC. Additionally, the effects of ficolin B proteins on macrophage polarization were proved in vitro.&#xD;Conclusion: This study suggested that the lung dECM hydrogel can reverse pulmonary fibrosis by suppressing M2 macrophage polarization through downregulation of the ficolin signaling pathway. Thus, the dECM hydrogel represent a promising class of biological materials for use in regenerative medicine.

Development and Evaluation of Poly(Lactic‐Co‐Glycolic Acid) Encapsulated Betulinic Acid Nanocarrier for Improved Anti‐Tumor Efficacy

AbstractBetulinic acid (BA) is a promising natural anti‐tumor agent renowned for its activity against various tumor cell types. Despite its favorable profile of low cytotoxicity to normal cells, BA's inherent hydrophobic nature and relatively short systematic half‐life impose hurdles for clinical application. This study introduces a strategy to surmount these obstacles by developing a drug delivery system employing poly(lactic‐co‐glycolic acid) (PLGA)‐encapsulated BA nanoparticles (PLGA‐BA NPs). Rigorous characterization techniques such as dynamic light scattering (DLS), x‐ray diffraction (XRD), and scanning electron microscopy (SEM) analyses are employed to confirm the integrity of the drug within the nanocarriers. The PLGA‐BA NPs demonstrated a mean particle size of 196 ± 6.80 nm. XRD analysis demonstrated the amorphous state of the PLGA‐BA formulation, a characteristic vital for sustained drug release and enhanced bioavailability. The PLGA‐BA NPs exhibited spherical morphology with encapsulation and loading efficiency of 83 ± 9.24% and 7.0 ± 0.4%, respectively, highlighting efficient encapsulation of the drug within the PLGA NPs. In vitro, cytotoxicity assessments demonstrated enhanced anti‐proliferative efficacy against breast and lung tumor cells when utilizing PLGA‐BA NPs in comparison to free BA. This research underlines the potential of employing the developed PLGA‐based nanocarrier to optimize the therapeutic efficacy of BA.

Natural Gomesin-like Peptides with More Selective Antifungal Activities

Background: Antimicrobial peptides are generally considered promising drug candidates for combating resistant bacterial infections. However, the selectivity of their action may vary significantly. Natural gomesin, isolated from haemocytes of the tarantula Acanthoscurria gomesiana, demonstrates a broad spectrum of antimicrobial activities, being the most effective against pathogenic fungi. Methods: Here, we searched for variants of natural gomesin-like peptides and produced their recombinant analogs in the bacterial expression system. The antimicrobial activities of the obtained peptides were tested against a panel of bacterial and yeast strains, and their toxicity towards human cells was examined. Results: Most of the new analogs of gomesin have primary structures homologous to that of the natural gomesin; however, they have fewer amino acid residues and post-translational modifications. One of the discovered analogs, the His-rich shorter peptide from the spider Dysdera sylvatica, designated as DsGom, displays antifungal activity comparable with that of natural gomesin. In the process of the structural–functional study of DsGom, it was shown that this analog retains a basic mechanism of action similar to that of natural gomesin. The DsGom analog has a significantly better toxicity profile as compared to gomesin. At the same time, the loss of the first Arg residue reduces, but does not annul, the antifungal activity of DsGom. Moreover, the acidification of the growth medium reduces the loss of the antifungal activity of this analog. Conclusions: The discovered natural gomesin-like peptides display more selective antifungal activities as compared to gomesin. The low cytotoxicity of DsGom, combined with its high antifungal activity and stability, allows us to consider it a promising drug candidate for the treatment of fungal infections, especially those caused by fungi of the Candida genus.

Screening of an Antibacterial and Coagulation Multifunctional Peptide and Its Application in Wound Healing.

As a new type of drug developed in the era of antibiotics, antimicrobial peptides (AMPs) have great potential in antibacterial, antiviral and antitumor aspects. Different from the principle of action of antibiotics, AMPs have a better effect on resisting drug-resistant bacteria. We synthesized a peptide library using solid-phase synthesis and successfully screened the antimicrobial peptide RKGAK. AMPs provide effective defense against both bacteria and fungi. Research has found that the lowest inhibitory concentrations of RKGAK against S. aureus, E. coli, and C. albicans are 75 μg/mL, 100 μg/mL, and 300 μg/mL. Not only that, this antibacterial peptide also has certain antiviral and coagulation effects. It is a multifunctional peptide that has great potential in many biomedical fields. It also has the advantages of being less likely to develop drug resistance, low hemolytic activity and low cytotoxicity. Loading the peptide into hydrogels has achieved good results in applications that promote wound healing.

Antimalarial and antimicrobial substances from the endophytic fungus Chaetomium globosum BCC71876

Three previously undescribed compounds including 2′,3′-dihydroxy-4,5′,4″-trimethoxy-p-terphenyl (1), 5-methoxyhydroperoxyco­chliodinol (2), and 5-(3′,3′-dimethylallyl)indole-3-oxoacetic acid (17), along with fifteen known compounds (3 – 16 and 18), were isolated from the endophytic fungus, Chaetomium globosum BCC71876. The chemical structures were determined by NMR spectral information as well as the comparison with those closely related compounds reported in the literature. The compounds isolated were evaluated for biological properties including antimalarial, anti-TB, anti-plant pathogenic fungal, antibacterial, and cytotoxicity. The isolated compounds exhibited a wide range of biological activities against the tested cell lines and showed very low cytotoxicity against both cancerous (MCF-7 and NCI-H187) and non-cancerous (Vero) cells, except for compounds 5, 10, 11, 17, and 18 (IC50 0.47 − 114.8 µM). Cochliodinol (5) had the strongest antimalarial activity (IC50 4.39 µM), whereas chaetomugilin J (11) showed the strongest anti-TB activity (MIC 3.13 µg/mL).

Differential cytotoxicity of methanol and water extracts from Bacopa monnieri (L.) Wettst and Ceratophyllum demersum L. on HepG2 and THLE2 cells

This study evaluated the cytotoxic effects of methanol and water extracts from Bacopa monnieri (L.) Wettst and Ceratophyllum demersum L. on HepG2 (liver cancer) and THLE2 (normal liver) cell lines using XTT assay. The extracts were tested at concentration range of 12.5-400 µg/mL. In HepG2 cells, the water extract of B. monnieri at 400 µg/mL exhibited the highest cytotoxicity, reducing cell viability to 11.08%, which was statistically significant (p &lt; 0.05) compared to other treatments. The methanol extract of C. demersum at 12.5 µg/mL had the least effect, maintaining 94.84% cell viability. For THLE2 cells, the water extract of B. monnieri (400 µg/mL) also showed the greatest reduction in cell viability (30.85%). The water extract of C. demersum at the same concentration resulted in similar viability (32.01%), with no significant statistical difference (p &gt; 0.05). The lowest concentrations of methanol and water extracts of C. demersum showed minimal effects (97.55% and 97.74% viability, respectively). Median inhibitor concentration (IC50) analysis revealed that B. monnieri’s water extract was most effective, with IC50 values of 68.45 µg/mL for HepG2 and 127.05 µg/mL for THLE2 cells. In contrast, C. demersum’s methanol extract had the highest IC50 values (173.35 µg/mL and 228.46 µg/mL, respectively), indicating lower cytotoxicity. Heatmap and cluster analyses highlighted the selective cytotoxicity of C. demersum on cancer cells with minimal effects on normal cells, showing its potential for targeted cancer therapy.

The Potential of Tecoma stans (Linn.) Flower Extract as a Natural Antioxidant and Anti-Aging Agent for Skin Care Products

Tecoma stans belongs to the Bignoniaceae family and possesses various pharmacological activities, including antimicrobial, anti-inflammatory, antifungal, antioxidant, and wound-healing activities. Although numerous studies have highlighted the beneficial effects of T. stans extracts, the impacts of different solvents on its biological activities, particularly its inhibitory effect on skin degradation enzymes (collagenase, elastase, and hyaluronidase assay), have not been reported. This study aims to explore the effects of different solvent extractions on the total phenolic and total flavonoid contents, antioxidant and anti-aging activities, and cytotoxicity. The most suitable extract was selected for incorporation into an anti-aging product. T. stans flowers were extracted using hexane, ethyl acetate, absolute ethanol, and deionized water through maceration. The aqueous extract yielded the highest extraction efficiency (40.73%), followed by absolute ethanol, ethyl acetate, and hexane. The phytochemical screening results revealed that all T. stans flower extracts contained phenolics, flavonoids, terpenoids, and alkaloids. Among the various solvents tested for T. stans flower extraction, absolute ethanol demonstrated the highest total phenolic content (24.10 ± 2.07 mg gallic acid equivalents (GAE)/g extract), followed by deionized water (20.83 ± 1.28 mg GAE/g extract). The highest total flavonoid content was observed in the ethyl acetate extract (205.11 ± 7.83 mg catechin equivalents (CE)/g extract), with ethanol showing a significantly lower concentration (140.67 ± 1.92 mg CE/g extract). In terms of antioxidant activity, the aqueous extract exhibited the most potent effects, with IC50 values of 0.600 ± 0.005 mg/mL for the DPPH• assay and 0.207 ± 0.001 mg/mL for the ABTS•+ assay. For anti-aging assays, the absolute ethanolic extract demonstrated the highest enzyme inhibition activity at 1 mg/mL, with collagenase, elastase, and hyaluronidase inhibition rates of 89.49% ± 2.96%, 94.61% ± 2.33%, and 82.56% ± 2.27%, respectively. Moreover, at a concentration of 50 µg/mL, the absolute ethanolic extract exhibited lower cytotoxicity, with human keratinocyte (HaCaT) cell viability of 78% ± 8.47%, which was significantly higher than that of the other extracts. An anti-aging gel containing 0.05% w/w of the ethanolic T. stans extract demonstrated physical and physicochemical stability during three months of storage at ambient temperatures, 4 °C, 45 °C, as well as after six cycles of heating/cooling tests. These findings suggest that the ethanolic extract of T. stans flower has potential as a safe and effective anti-aging agent for cosmeceutical products.

Evaluation of In Vitro Inhibition of β-Hematin Formation: A Step Towards a Comprehensive Understanding of the Mechanism of Action of New Arylamino Alcohols

Currently, artemisinin-based combination therapy is recommended as first-line treatment of uncomplicated falciparum malaria. Arylamino alcohols (AAAs) such as mefloquine (MQ) are the preferred partner drugs due to their longer half-life, reliable absorption and strong antimalarial activity. However, the mode of action of MQ remains poorly understood and its neurotoxicity limits its use. Furthermore, the emergence of drug-resistant parasites requires development of new antimalarial drugs. The aim of this study was to evaluate the β-hematin inhibition capacity of three pairs of enantiopure AAAs 1–3 (a/S and b/R) derived from MQ or enpiroline (ENP), a pyridine-based MQ analog with strong antimalarial activity. Inhibition of β-hematin—the synthetic counterpart of hemozoin formation—was determined for each compound. Antimalarial activity against W2 and 3D7 Plasmodium falciparum strains as well as percentages of inhibition of β-hematin formation were compared to those of reference molecules, i.e., chloroquine (CQ), MQ and ENP. Furthermore, a cytotoxicity study on the human-derived hepatocarcinoma cell line HepG2 was performed. With high antimalarial activity, stronger ability to inhibit β-hematin formation and low cytotoxicity, AAAs 1a-b and 2a are the most promising. These findings provide a better understanding of their potential mechanisms of action and may pave the way toward developing new lead compounds.

Design, Synthesis, and Biological Evaluation of Novel 2-Heteroaryl-oxazolidine-4-one Derivatives as Novel HBV Capsid Assembly Modulators.

Using 2-pyrazole oxazolidine-4-one derivative 1 as the lead compound, a series of novel 2-heteroaryl-oxazolidine-4-one derivatives were designed and synthesized by replacing pyrazole moiety with other heterocycles, including methyl pyrazole, oxazole, thiazole, triazole, and reverse pyrazoles, based on the principle of bioisosterism. The structures of target compounds were established by 1H-NMR, 13C-NMR, and electrospray ionization (ESI)-MS. Majority of these compounds showed moderate to good inhibitory activities against hepatitis B virus (HBV) DNA proliferation with low cytotoxicities. Especially, compound 7g showed the most potent anti-HBV activity with EC50 value of 0.059 µM, accompanied with better selectivity index (SI) value than that of lead compound. Our research revealed the structure-activity relationship (SAR) of these newly designed compounds and compound 7g was identified as the potential HBV capsid assembly modulator.

Identification of cepharanthine as an effective inhibitor of African swine fever virus replication

ABSTRACT African swine fever virus (ASFV) causes highly contagious swine disease, African swine fever (ASF), thereby posing a severe socioeconomic threat to the global pig industry and underscoring that effective antiviral therapies are urgently required. To identify safe and efficient anti-ASFV compounds, a natural compound library was screened by performing an established cell-based ELISA in an ASFV-infected porcine alveolar macrophage (PAM) model. In total, 6 effective anti-ASFV compounds with low cytotoxicity were identified. Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid, was the most potent inhibitor effect with an IC50 of 0.3223 μM. To further investigate the mechanism through which CEP inhibits ASFV replication, transcriptome profiles were generated in PAMs treated with CEP and/or infected with ASFV. ASFV infection dramatically altered immune response-associated gene expression. CEP treatment upregulated the expression of cholesterol biosynthesis-related genes, regardless of infection status. According to time-of-addition experiments, CEP primarily exerts its antiviral effect during the early stages of ASFV infection, specifically by inhibiting viral entry. Transcriptomic analysis suggested that CEP blocks ASFV entry through the clathrin-mediated endocytosis pathway by increasing EHD2 gene expression in macrophages. Disrupting EHD2 with small interfering RNA promoted ASFV entry into clathrin-positive vesicles. Finally, the protective effect of CEP in vivo was evaluated using ASFV-infected pigs. CEP could provide partial protection against ASFV infection, as indicated by an increase in survival time from 9.67 days to 16.67 days. Our findings imply that CEP exhibits potential antiviral activity against ASFV infection in PAMs, positioning it as a promising therapeutic strategy for ASF.

Simultaneous elimination mechanism of formaldehyde and acrolein by resveratrol in food and the cytotoxicity of the products.

Polyphenols have been intensively investigated for scavenging single harmful aldehydes, such as formaldehyde (FA) and acrolein (ACR). However, there is a lack of studies on the effect and mechanism of eliminating co-existing harmful aldehydes by polyphenols. In this study, resveratrol (RV) was found to simultaneously scavenge FA and ACR by forming various adducts, with the RV-ACR adduct (RA, molecular formula: C17H16O4) and RV-ACR-FA adduct (RAF, molecular formula: C18H18O5) being the dominant ones. The elimination of co-existing FA and ACR by RV were further confirmed in real food systems. RA (IC50, 67.22 and 147.70μM in GES-1 and Caco-2 cells, respectively) and RAF (127.50 and over 250μM, respectively) showed significantly lower cytotoxicity than the co-existing FA and ACR (18.27 and 5.26μM, respectively) in the gastrointestinal cell lines. This study provided data support for food safety control by employing RV as a dietary supplement to scavenge harmful aldehydes in foods.

Ellagic Acid Potentiates the Inhibitory Effects of Fluconazole Against Candida albicans

Background/Objectives: Antifungal resistance to azoles, coupled with the increasing prevalence of Candida albicans infections, represents a significant public health challenge and has driven the search for new natural compounds that can act as alternatives or adjuvants to the current antifungals. Ellagic acid (EA) has demonstrated antifungal activity; however, its effects are not fully understood. In this study, we investigated the in vitro anti-Candida activity of EA and its ability to potentiate the effects of fluconazole (FLZ) on C. albicans. Methods: The Minimum Inhibitory Concentration (MIC) of EA was determined by broth microdilution and its interaction with FLZ was assessed using a checkerboard assay. Additionally, we examined the effects of EA on yeast-to-hypha transition, inhibition of biofilm formation, time–kill kinetics, hemolytic activity, and cytotoxicity in HeLa ATCC® CCL-2™ cells. Results: EA exhibited MIC values ranging from 250 to 2000 µg/mL and showed synergistic and additive interactions with FLZ, resulting in a marked reduction in the MIC values of FLZ (up to 32-fold) and EA (up to 16-fold). In the time–kill assay, the most effective combinations were 4× EA MIC, 2× EA MIC, and FIC EA + FLZ, which showed fungicidal activity. Furthermore, EA did not show hemolytic activity and demonstrated low and dose-dependent cytotoxicity in HeLa cells, with no cytotoxic effects observed in combination with FLZ. EA and the synergistic combination of EA and FLZ interfered with both the yeast-to-hypha transition process in C. albicans cells and biofilm formation. In addition to its antifungal efficacy, EA demonstrated a favorable safety profile at the concentrations used. Conclusions: This study presents promising results regarding the potential use of EA in combination with FLZ for the treatment of C. albicans infections.

Liposomal and Nanostructured Lipid Nanoformulations of a Pentacyclic Triterpenoid Birch Bark Extract: Structural Characterization and In Vitro Effects on Melanoma B16-F10 and Walker 256 Tumor Cells Apoptosis

Background/Objectives: Pentacyclic triterpenoids are increasingly studied as anticancer agents with many advantages compared to synthetic chemotherapeutics. The aim of this study was to prepare liposomal and nanostructured lipid formulations including a standardized extract of silver birch (Betula pendula) outer bark (TTs) and to evaluate their potential as anticancer agents in vitro, using Melanoma B16-F10 and Walker carcinoma cells. Methods: Appropriate solvents were selected for efficient TTs extraction, and original recipes were used to obtain Pegylated liposomes and nanolipid complexes with entrapped TTs, comparative to pure standards (betulinic acid and doxorubicin) in similar conditions. The composition, morphology, and sizes of all nanoformulations were checked by high-performance liquid chromatography/mass spectrometry, Transmission Electronic Microscopy, and Diffraction Light Scattering. The entrapment efficiency and its impact on cell viability, cell cycle arrest, and apoptosis by flow cytometry was also measured on both cancer cell lines. Conclusions: The standardized TTs, including betulin, lupeol, and betulinic acid, showed good stability and superior activity compared to pure betulinic acid. According to experimental data, TTs showed good entrapment in liposomal and NLC nanoformulations, both delivery systems including natural, biodegradable ingredients and enhanced bioavailability. The apoptosis and necrosis effects were more pronounced for TTs liposomal formulations in both types of cancer cells, with lower cytotoxicity compared to Doxorubicin, and can be correlated with their increased bioavailability.

A Fully Degradable, Bio‐Safe Supercapacitor Targeting for Harmless Disposal of Energy Storage Devices

ABSTRACTSupercapacitors show broad application prospects as promising energy supply units for future integrated or even implantable electronic devices, but their poor degradability and high biotoxicity severely limit their further development. Regarding this, future‐oriented supercapacitors with fully degradable behavior and excellent biosafety have been prepared through the wide application of degradable polymers and a rational encapsulation and isolation strategy. The combination of self‐supporting pulp fiber/graphene composite electrodes and guar gum gel electrolyte endows the devices with ideal rate performance and long lifetime. The devices demonstrate extremely low cytotoxicity and satisfactory biocompatibility. The implantation caused no significant rejection and did not affect the survival status of the SD rats, suggesting the possibility of powering implantable electronics. Notably, all components of the device (electrodes, electrolyte, substrate, and encapsulation materials) do not contain hazardous or non‐degradable materials, allowing for true complete degradability. The preparation strategy and material selection in the study are expected to be generalized to a wide range of energy storage systems, providing some reference and guidance for the harmless disposal of energy storage devices and even microelectronics. image

Discovery of Non-Covalent Inhibitors for SARS-CoV-2 PLpro: Integrating Virtual Screening, Synthesis, and Experimental Validation.

The SARS-CoV-2 pandemic has significantly challenged global public health, highlighting the need for effective therapeutic options. This study focuses on the papain-like protease (PLpro) of SARS-CoV-2, which is a critical enzyme for viral polyprotein processing, maturation, and immune evasion. We employed a combined approach that began with computational models in a virtual screening campaign, prioritizing compounds from our in-house chemical library against PLpro. Out of 81 virtual hits evaluated through enzymatic and biophysical assays, we identified a modest inhibitor featuring a naphthyridine core with an IC50 of 73.61 μM and a K i of 22 μM. Expanding our exploration, we synthesized and assessed 30 naphthyridine analogues, three of which emerged as promising noncovalent, nonpeptidomimetic inhibitors with IC50 values between 15.06 and 51.81 μM. Furthermore, in vitro ADMET assays revealed these compounds to possess moderate aqueous solubility, low cytotoxicity, and high microsomal stability, making them excellent candidates for further development targeting SARS-CoV-2 PLpro.