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Purpose: To assess the antioxidant and antineoplastic effects of Hibiscus sabdariffa Linn. on oral squamous cell carcinoma cells. Materials and Methods: Human squamous cell carcinoma HSCC cells were tested for cytotoxicity by a methanol extract of Hibiscus sabdariffa (MEHSP). After 24, 48, and 72 h, the MTT assay and Trypan blue exclusion test were used to determine cell survival and death. 2, 2-diphenyl-1-picrylhydrazyl (DPPH), DNA Protection Assay (DPA), and ferric reducing antioxidant power assay (FRAPA) measured the antioxidant activity of MEHSP. Results: The antioxidant activity (%) ranged from 47.92-82.24 in the DPPH test, 11.61-73.65 in the DPA, and 4.97-52.09 in the FRAPA. The HSCC in-vitro cytotoxicity assay showed dose- and time-dependent cell viability. MEHSP at 5 μg/ml inhibited viable cells, while increasing MEHSP doses decreased cell viability. The Trypan blue exclusion test showed that MEHSP significantly reduced cell viability at 24, 48, and 72 h. Conclusion:Hibiscus sabdariffa contains antioxidant and HSCC-cytotoxic properties. [ABSTRACT FROM AUTHOR]

Lithium disilicate (LD) glass-ceramics used for bone repair need to have good mechanical properties and biological activity. Ion-exchange can lead a significant surficial strengthening and bioactivity of LD glass-ceramics. In this work, LD glass-ceramics were Li+/Ca2+@Li+/K+ exchanged in a mixed salt bath of 30 % Ca(NO 3) 2 + 70 % KNO 3 (in mol %) at 400 °C for 16 h, 32 h and 64 h respectively. LD glass-ceramics were significantly strengthened after Li+/Ca2+@Li+/K+ exchange. However, due to the shallow depth of the ion-exchange layer and stress relaxation, the strengthening effect deteriorated with the prolongation of the ion-exchange time. The Li+/Ca2+@Li+/K+ exchanged LD glass-ceramics could be conducive to the formation of the hydroxyapatite (HA) after soaking in the simulated body fluid (SBF). Moreover, the protein adsorption, cytotoxicity, cell adhesion, osteoblast proliferation and alkaline phosphatase (ALP) activity expression of Li+/Ca2+@Li+/K+ exchanged LD glass-ceramics were investigated. Ca2+ release might promote the bioactivity of ion-exchanged LD glass-ceramics. Therefore, Li+/Ca2+@Li+/K+ exchange can improve the mechanical properties and bioactivity of LD glass-ceramics, which has important significance for its application in orthopedic reconstruction. [ABSTRACT FROM AUTHOR]

Although various iron-based magnetic materials have been extensively studied in biomedical field for many years, iron boride compounds with interesting chemical and magnetic properties are relatively less explored, and their potential applications are not as widely known. In this study, the synthesis, coating, surface modification, and cytotoxicity tests of the Fe–Zn–B system were presented. Iron boride-based nanoparticles (NPs) containing elemental zinc (Zn) were developed by using a direct chemical synthesis of FeCl 3 , ZnCl 2 and NaBH 4 , and investigated for potential use in biomedical applications. Powders having the phases of pure FeB with small amount of elemental Zn were obtained with a uniform morphology and an average particle size of 68 nm. The NPs were then coated with oleic acid (OA) and surface modified with sodium tricitrate, to increase their stability and biocompatibility, and well-dispersed NPs were obtained with sizes below 30 nm. TEM investigations revealed the presence of hybrid clusters with nanoparticle – OA structures, indicating that FeB nanoparticles were stabilized by being embedded in OA clusters, forming both agglomerated sub-micron and free nano-sized structures. Obtained NPs showed ferromagnetic property, with a saturation magnetization of 25.9 emu/g and a low coercivity of 90 Oe. As a result of testing different types of healthy and cancer cell lines with NPs, Zn-doped-FeB@OA NPs exhibited a high biocompatibility. Results suggested that highly biocompatible and magnetic OA-coated Zn-doped FeB particles can be potential candidates for biomedical applications such as medical imaging or drug delivery systems. [ABSTRACT FROM AUTHOR]

The zinc doped calcium phosphate biomaterials have recently attracted much attention. In this study, we have investigated the bioactivity, cytotoxicity and antibacterial activity of zinc doped calcium phosphate-sulfate hydroxyapatites Ca 9-x Zn x Na(PO 4) 5 (SO 4)(OH) 2 (x = 0, 0.2, 0.5). The samples have been synthesized by the solid-state reaction at high temperature and then have been characterized using X-ray diffraction, Infrared spectroscopy and Raman scattering spectroscopy. The surface analysis was conducted by scanning electron microscopy (SEM) in combination with energy-dispersive spectroscopy (EDX) and Zeta-potential measurements. The bioactivity investigation involved immersing the samples in a simulated body fluid (SBF), providing valuable insights into the samples capability to stimulate the formation of an apatite layer similar to that found in bones. The antibacterial activity of the materials was studied using pathogenic bacteria. The assessment of sample cytotoxicity was involved using artemia salina as the experimental model. X-ray diffraction patterns reveal that the samples crystallize in the hexagonal system with the P 6 3 / m space group. The x = 0.2 material exhibited the best crystallinity and the highest negative Zeta potential, making it the most bioactive sample when immersed in simulated body fluid (SBF). SEM analysis confirmed that this sample effectively promotes the formation of a new apatite layer, highlighting its promising potential for biomedical applications. The results of the study highlight the significantly beneficial effect of doped hydroxyapatite (x = 0.2) on the biological properties, compared to the other samples analyzed in this study, thus underscoring the strong potential of this material for promising applications in the fields of bioengineering and tissue regeneration. [ABSTRACT FROM AUTHOR]

Electrochemical anodization, under a constant voltage of 45 V and for 15, 30, and 45 min, was performed to fabricate highly ordered TiO 2 nanotubes. Depending on the processing paramters, the diameter of the TiO 2 nanotubes was found to be around 95 ± 6 nm, while the thickness of TNT layer exhibited a change with anodizing time, varying from 1 to 4 μm. Subsequent to the anodization α-Fe 2 O 3 /TiO 2 heterogeneous structure was created by the spin coating of iron precursor based solutions on TiO 2 nanotubes. X-ray diffraction (XRD) and scanning electron microscopy (SEM) analysis were utilized to ascertain the phase structure and morphology of TiO 2 nanotubes. The change of optical band gap values depending on the processing parameters was calculated using UV–Vis spectrophotometer data. The photocatalytic performances of the samples, namely the degradation rates and kinetics, were evaluated by examining the photodegradation of methylene blue (MB). The (TC15) sample, obtained by anodizing for 15 min and decorated with α-Fe 2 O 3 , exhibited the highest photocatalytic activity, with a degradation efficiency of 70 % at the end of 7 h of light exposure. On the other hand, the inhibition percentages of bacterial growth were examined and it was seen that the TC30 sample with the highest value was 88.89 % for E.coli bacteria and 70.57 % for S.aureus. To assess the mechanism of antimicrobial activity, ROS (Reactive Oxygen Species) Analysis were perfomed on T30 and TC30 groups and the ROS amount of TC30 was higher than T30. According to the results of the L929 mouse fibroblast cytotoxicity experiment with indirect contact according to ISO 10993-5 standards, all samples showed a successful performance in terms of cell viability. The cell viability of TC15 was higher in comparison to the control group. [ABSTRACT FROM AUTHOR]

Humans have been using plants in the treatment of various diseases for millennia. Currently, even with allopathic medicines available, numerous populations globally still use plants for therapeutic purposes. Although plants constitute a safer alternative compared to synthetic agents, it is well established that medicinal plants might also exert adverse effects. Thus, the present investigation aimed to assess the phytotoxic, cytotoxic, and genotoxic potential of two plants from the Brazilian Cerrado used in popular medicine, Davilla nitida (Vahl) Kubitzki, and Davilla elliptica (A. St.-Hil.). To this end, germination, growth, and cell cycle analyses were conducted using the plant model Lactuca sativa. Seeds and roots were treated with 0.0625 to 1 g/L for 48 hr under controlled conditions. The germination test demonstrated significant phytotoxic effects for both species at the highest concentrations tested, while none of the extracts produced significant effects in the lettuce growth test. In the microscopic analyses, the aneugenic and cytotoxic action of D. elliptica was evident. In the case of D. nitida greater clastogenic action and induction of micronuclei, (MN) were noted suggesting that the damage initiated by exposure to these extracts was not repaired or led to apoptosis. These findings indicated that the observed plant damage was transmitted to the next generation of cells by way of MN. These differences in the action of the two species may not be attributed to qualitative variations in the composition of the extracts as both are similar, but to quantitative differences associated with synergistic and antagonistic interactions between the compounds present in these extracts. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive type of skin cancer, with few therapeutic alternatives following metastasis development. In recent years, drug delivery-associated nanotechnology has shown promising targeted results with diminished adverse effects compared to conventional treatments. This study aimed to (1) examine the effects of plant-derived α-arbutin, a natural compound and (2) compare these findings with bioactively developed liposomes containing α-arbutin utilizing the B16-F10 murine melanoma cell line as a model. Liposomes were obtained through reversed-phase evaporation by applying a spray dryer to assess their stability. The following biologic assays were measured cytotoxicity/antiproliferative (MTT, Neutral Red, and dsDNA PicoGreen). In addition, the levels of melanin and purinergic enzymes were also measured. The production of reactive oxygen species (ROS) and nitric oxide (NO) was determined as a measure of oxidative state. Treatment with nano-liposome containing alpha-arbutin induced a significant 68.4% cytotoxicity, similar to the positive control, in the B16-F10 murine melanoma cell line at 72 hr. Further, arbutin and liposomes containing alpha-arbutin increased levels of ROS and nitrite formation at 72 hr at the highest concentration (100 and 300 µg/ml) of treatments. Arbutin and liposomes containing alpha-arbutin reduced melanin levels at all tested concentrations. In addition, arbutin and alpha-arbutin containing liposomes lowered nucleotides (AMP, ADP, and ATP) and nucleoside (adenosine) levels in melanoma cells. Evidence suggests that α-arbutin containing liposome can be considered as an alternative immunosuppressive agent stimulated in melanoma treatment. [ABSTRACT FROM AUTHOR]

• Astrocytes-derived EVs reduce cytotoxicity in HBECs treated with Na 2 Cr 2 O 7. • Exposure to Na 2 Cr 2 O 7 suppressed immune response genes. • Astrocyte-derived EVs affect lncRNA expression that regulates brain development. • Exposure to Na 2 Cr 2 O 7 is associated with an increase in 8OHdG genomic levels. This study investigates the therapeutic effect of astrocyte-derived extracellular vesicles (EVs) in mitigating neurotoxicity-induced transcriptome changes, mitochondrial function, and base excision repair mechanisms in human brain endothelial cells (HBECs). Neurodegenerative disorders are marked by inflammatory processes impacting the blood–brain barrier (BBB) that involve its main components- HBECs and astrocytes. Astrocytes maintain homeostasis through various mechanisms, including EV release. The effect of these EVs on mitigating neurotoxicity in HBECs has not been investigated. This study assesses the impact of astrocyte-derived EVs on global transcriptome changes, cell proliferation, cytotoxicity, oxidative DNA damage, and mitochondrial morphology in HBECs exposed to the neurotoxic reagent Na 2 Cr 2 O 7. Exposure to Na 2 Cr 2 O 7 for 5 and 16 h induced oxidative DNA damage, measured by an increase in genomic 8OHdG, while the EVs reduced the accumulation of the adduct. A neurotoxic environment caused a non-statistically significant upregulation of the DNA repair enzyme OGG1 while the addition of astrocyte-derived EVs was associated with the same level of expression. EVs caused increased cell proliferation and reduced cytotoxicity in Na 2 Cr 2 O 7 -treated cells. Mitochondrial dysfunction associated with a reduced copy number and circular morphology induced by neurotoxic exposure was not reversed by astrocyte-derived EVs. High-throughput RNA sequencing revealed that exposure to Na 2 Cr 2 O 7 suppressed immune response genes. The addition of astrocyte-derived EVs resulted in the dysregulation of long noncoding RNAs impacting genes associated with brain development and angiogenesis. These findings reveal the positive impact of astrocytes-derived EVs in mitigating neurotoxicity and as potential therapeutic avenues for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

A series of C21 steroidal glycosides were isolated from the root bark of Periploca sepium, including a new compound, perisepiumoside A1 (1), and six known compounds (2-7). Their structures were elucidated by analysis of HR-ESI-MS, and 1D and 2D NMR spectroscopic data. All these compounds were tested for their NO production inhibitory activity in LPS-stimulated RAW 264.7 cells. Results showed that these C21 steroidal glycosides could remarkably inhibit NO production, particularly 1 and 2 with IC50 values of 30.81 ± 0.18 μM and 44.39 ± 0.21 μM, respectively. In addition, the cytotoxicity of these compounds was measured on A549, MCF-7, and HeLa cancer cell lines. Among them, compounds 1 and 7 displayed cytotoxicity against the A549 cell line with IC50 values of 28.41 ± 0.12 μM and 39.06 ± 0.05 μM, respectively. [ABSTRACT FROM AUTHOR]

The leaves of Citrus deliciosa Tenore were collected in southern Brazil, dried, and subjected to the hydrodistillation process to obtain the essential oil. The extraction of essential oil yielded 0.97% ± 0.04. The chromatographic profile of this compound revealed 11 substances, being methyl N-methyl-anthranilate (75.1%), γ-terpinene (13.8%), and Limonene (7%) as major substances. The essential oil shows antifungal action against all tested yeasts, with promising action against Cryptococcus neoformans, Cryptococcus gattii, and Trichosporon asahii. This compound was also able to inhibit the biofilm production of Candida albicans, Candida glabrata, Candida parapsilosis, and T. asahii. The essential oil of tangerine showed weak antioxidant action. It did not show cytotoxicity in human mononuclear cells. It is hoped that these results may guide future studies for the production of formulations that can be used in the treatment of biofilms caused by yeasts, as well as in candidiasis, cryptococcosis, and/or trichosporonosis. [ABSTRACT FROM AUTHOR]

Natural products, especially fungal secondary metabolites, have been served as valuable sources of drug leads in pharmaceutical industry. Medicinal plants-associated endophytic fungi possess a well-developed secondary metabolism. In this study, chemical investigation on Penicillium ochrochloron YT2022-65, an endophytic fungus associated with Lonicera Japonica, led to the isolation of six structurally diversified indole alkaloids, including a new one, namely peniochroloid A (1), as well as five previously reported alkaloids, flavonoid B (2), brocaeloid C (3), isoroquefortine C (4), roquefortine C (5), and dihydrocarneamide A (6). Their structures, including the absolute configuration of 1, were determined by a combined analysis of HRESIMS, NMR spectroscopic data, and calculation of the optical rotation. Their cytotoxicity against A549, HepG2, MCF-7, and THP-1 cell lines were evaluated in vitro. The new compound 1 was found to possess considerable cytotoxicity against MCF-7 and THP-1 cell lines with IC50 values of 10.2 and 11.0 μM, respectively. [ABSTRACT FROM AUTHOR]

A new lactone, collectindolide (1), as well as three known compounds, (S)-sydonic acid (2), (S)-hidroxysydonic acid (3), and indole-3-aceticacid (4) were obtained from the liquid media of Colletotrichum gloeosporioides, which was obtained from Artocarpus heterophyllus. The chemical structures of 1-4 were established by spectroscopic analyses, including NMR experiments and by HR-ESI-TOF-MS mass spectroscopy. Compounds 1-4 were evaluated for their cytotoxicity against murine leukaemia P-388 cell lines by MTT assay. Antibacterial activity of compounds 1-4 was also assayed against four bacteria. Phytochemical investigation of the genus Colletotrichum derived from the plant genus Artocarpus is reported for the first time. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus generates extracellular membrane vesicles (MVs) during both in vitro culture and in vivo infection. S. aureus MVs are generated by either blebbing of the cytoplasmic membrane or explosive cell lysis. Proteins and nucleic acids encapsulated within S. aureus MVs are protected from degradation or neutralization by host factors. S. aureus MVs exhibit cytotoxicity to a variety of host cell types and induce both host innate and adaptive immune responses in animal infection models. MVs exploit different endocytic pathways for the delivery of their cargo into host cells. Deciphering the intracellular fate of S. aureus MVs after cellular entry may deepen our limited understanding of how MVs impact the host during staphylococcal infections. Staphylococcus aureus is an important bacterial pathogen that causes a wide variety of human diseases in community and hospital settings. S. aureus employs a diverse array of virulence factors, both surface-associated and secreted, to promote colonization, infection, and immune evasion. Over the past decade, a growing body of research has shown that S. aureus generates extracellular membrane vesicles (MVs) that package a variety of bacterial components, many of which are virulence factors. In this review, we summarize recent advances in our understanding of S. aureus MVs and highlight their biogenesis, cargo, and potential role in the pathogenesis of staphylococcal infections. Lastly, we present some emerging questions in the field. [ABSTRACT FROM AUTHOR]

Guinea grass seed starch nanoparticles (GSNPs) Were prepared via nanoprecipitation and dual‐modified with 3% octenyl succinic anhydride (OSA) and pulsed electric fields (PEF) (1.5, 3.0, and 4.5 kV cm⁻¹). Native and modified GSNPs Were assessed for cytotoxicity (Caco‐2 cells), in vitro digestibility, and their ability to stabilize Pickering emulsions. The cytotoxicity results showed no significant impact on cell viability or metabolic activity across all concentrations and modifications. The digestibility profile revealed that native GSNPs Were more digestible (62.61%) compared to modified samples (53.49%). The logarithmic slope analysis indicated that the digestion profiles of all samples followed a linear trend (r² 〉 0.86), characterized by first‐order kinetics. Pickering emulsions containing 0.25–2% GSNPs exhibited good stability, with higher concentrations (1–2%) ensuring 100% emulsified phase coverage and excellent storage stability. Droplet sizes ranged from 171.32 to 536.41 nm, and zeta potentials from −28.68 to −9.87 mV over two months. Microscopy confirmed that all emulsion droplets Were spherical, with smaller droplet sizes observed. The emulsions displayed shear‐thinning flow behavior, where apparent viscosity decreased with increasing shear rate, and increased with modification. These findings suggest that GSNPs have significant potential for use in forming stable Pickering emulsions. [ABSTRACT FROM AUTHOR]

In this study, phenyl (1,4,6-triphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methanone was obtained by using the Biginelli reaction method. The structure of this compound was analyzed using elemental analysis, IR, 1H, and 13C NMR. The quantum chemical calculations (QCC) of this compound were performed density functional theory (DFT) method, 6–31 G (d, p) base set, and B3LYP functions with the Gaussian09W software package. Literature shows that pyrimidine-derived compounds have very active biological properties. For this reason, the biologically active properties of the synthesized compound were also examined. To determine embryotoxic, genotoxic, and cytotoxic effects of compound, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, micronucleus (MN) and 8-OH-dG assays were carried out. On the other hand, pharmacokinetic and toxicity properties (ADMET) were predicted in silico via SwissADME and Protox-II web tools. In silico estimates of this compound used in the study showed that the compound has the covetable physicochemical properties for bioavailability. In conclusion, the obtained results of our study clearly showed that this compound exerted strong toxicity potential. [ABSTRACT FROM AUTHOR]

In the present investigation, we employed the hydrothermal approach for crafting mesoporous KIT-6 scaffolds and the post-impregnation technique for incorporating the drug. The concentration of berberine within the mesoporous channels of KIT-6 was assessed through UV–visible spectrophotometer. The results showed that the drug molecules were well integrated into the structure of KIT-6, displaying the material's 3D cubic mesoporous shape and its notable specific surface area of 1376 m2/g. The in vitro drug release profile was investigated in phosphate-buffered saline (pH = 6.8), and the findings point to the possibility of controlling the drug release quantity by loading the drug into the carrier. Using Vero cell lines, the toxicity of the drug-free and drug-loaded samples was examined and it was concluded that by adding berberine to the mesoporous matrix, the drug's toxicity was dramatically lowered. [ABSTRACT FROM AUTHOR]

According to the World Health Organization, cancer is a leading cause of death worldwide. Several bioactive molecules, such as peptides, have been developed to adjuvate in cancer therapy. Previous evidence showed that the peptides KLKKNL, MLKSKR, KKYRVF, FRTKKK, and SVVAKAPVGKR, identified from a protein fraction of S. hispanica seeds, may serve as adjuvant therapy based on their physicochemical properties. Thus, this work aimed to evaluate the cytotoxic effect of these peptides on cancer cells through in silico and in vitro assays. Molecular dynamics simulations were performed to determine the interaction of the peptides with a cancer cell membrane model. Additionally, cell viability assays were performed to assess the effect of the peptides on MCF-7, Caco2, HepG2, DU145, HeLa, and hFB cell lines, and on erythrocytes. Both in silico and in vitro evaluations reported that KLKKNL, MLKSKR, KKYRVF, FRTKKK, and SVVAKAPVGKR interacted with the cancer cell membrane, significantly decreasing their viability. Molecular dynamics of KKYRVF exhibited a stable interaction with the cancer cell membrane model (-3.2 Kcal·mol-1), and experimentally showed selective cytotoxicity on the cancer cell lines. These findings support the continuous assessment of these peptides as adjuvants in cancer treatment for their potential as ingredients in functional foods or nutraceuticals. [Display omitted] • Lung, colorectum, liver and breast cancers are the top types of cancer to cause death. • In silico and in vitro assays successfully predict the anticancer activity of peptides. • KLKKNKL, MLKSKR, KKYRVF, FRTKKK, and SVVAKAPVGKR report anticancer properties. • The five peptides reported interaction with the cancer cell membrane in silico. • The predictions were validated since the peptides decreased the cancer cells' viability. [ABSTRACT FROM AUTHOR]

BamA, an Omp85 superfamily member, is universally conserved and essential for cell viability. Using anti‐Oma87 antibodies, we focus on understanding the effect of Oma87 of Acinetobacter baumannii on pathogenicity. Oma87 was expressed, purified, and used to induce anti‐Oma87 antibodies in BALB/c mice. Acute toxicity of the protein was evaluated in mice. HeLa cells were infected with both live and killed A. baumannii 19606 and a clinical isolate. The effects of anti‐Oma87 sera on A. baumannii adherence, internalization, and proliferation in HeLa cells were studied. The roles of microfilaments and microtubules in A. baumannii invasion were demonstrated by Actin disruption. Reduced bacterial population and biofilm formation were noted. The ability of A. baumannii to provoke autophagy through Oma87 induction leads to incomplete autophagy and potentially facilitates bacterial replication. Actin‐mediated uptake, attachment, and invasion demonstrated A. baumannii survival and multiplication within vacuoles in the host cell. The findings underscore the potential of Oma87 as a therapeutic intervention target in infections caused by A. baumannii. This comprehensive analysis contributes valuable information for understanding the virulence mechanisms of A. baumannii, potentially guiding future strategies to combat infections caused by this pathogen. [ABSTRACT FROM AUTHOR]

In this work, we conceived and developed antibody-drug conjugates (ADCs) that could efficiently release the drug after enzymatic cleavage of the linker moiety by tumoral proteases. The antibody-drug linkers we used are the result of a rational optimization of a previously reported PEGylated linker, PUREBRIGHT® MA-P12-PS, which showed excellent drug loading capacities but lacked an inbuilt drug discharge mechanism, thus limiting the potency of the resulting ADCs. To address this limitation, we chose to incorporate a protease-sensitive trigger into the linker to favor the release of a "PEGless" drug inside the tumor cells and, therefore, obtain potent ADCs. Currently, most marketed ADCs are based on the Val-Cit dipeptide followed by a self-immolative spacer for releasing the drug in its unmodified form. Here, we selected two untraditional peptide sequences, a Phe-Gly dipeptide and a Val-Ala-Gly tripeptide and placed one or the other in between the drug on one side (N-terminus) and the rest of the linker, including the PEG moiety, on the other side (C-terminus), without a self-immolative group. We found that both linkers responded to cathepsin B, a reference lysosomal enzyme, and liberated a PEG-free drug catabolite, as desired. We then used the two linkers to generate ADCs based on trastuzumab (a HER2-targeting antibody) and DM1 (a microtubule-targeted cytotoxic agent) with an average drug-to-antibody ratio (DAR) of 4 or 8. The ADCs showed restored cytotoxicity in vitro , which was proportional to the DM1 loading and generally higher for the ADCs bearing Val-Ala-Gly in their structure. In an ovarian cancer mouse model, the DAR 8 ADC based on Val-Ala-Gly behaved better than Kadcyla® (an approved ADC of DAR 3.5 used as control throughout this study), leading to a higher tumor volume reduction and more prolonged median survival. Taken together, our results depict a successful linker optimization process and encourage the application of the Val-Ala-Gly tripeptide as an alternative to other existing protease-sensitive triggers for ADCs. [Display omitted] • Hydrophilic linkers are necessary to accommodate high drug loadings on antibodies. • The proposed linker features two pendant PEG arms to create a hydrated shell around the drug. • The proposed linker uses a protease-sensitive trigger for controlled "PEGless" drug release. • The linker optimization process led to a DAR 8 ADC active in a xenograft tumor model. [ABSTRACT FROM AUTHOR]

The proven efficacy of immunotherapy in fighting tumors has been firmly established, heralding a new era in harnessing both the innate and adaptive immune systems for cancer treatment. Despite its promise, challenges such as inefficient delivery, insufficient tumor penetration, and considerable potential toxicity of immunomodulatory agents have impeded the advancement of immunotherapies. Recent endeavors in the realm of tumor prophylaxis and management have highlighted the use of living biological entities, including bacteria, oncolytic viruses, and immune cells, as a vanguard for an innovative class of live biotherapeutic products (LBPs). These LBPs are gaining recognition for their inherent ability to target tumors. However, these LBPs must contend with significant barriers, including robust immune clearance mechanisms, cytotoxicity and other in vivo adverse effects. Priority must be placed on enhancing their safety and therapeutic indices. This review consolidates the latest preclinical research and clinical progress pertaining to the exploitation of engineered biologics, spanning bacteria, oncolytic viruses, immune cells, and summarizes their integration with combination therapies aimed at circumventing current clinical impasses. Additionally, the prospective utilities and inherent challenges of the biotherapeutics are deliberated, with the objective of accelerating their clinical application in the foreseeable future. This abstract graphic takes concerted action with abstract section and illustrates the engineered live oncolytic biotherapeutics (microbe/virus/cells) from preclinical research to clinical progress. [Display omitted] [ABSTRACT FROM AUTHOR]

Breast cancer represents the most prevalent tumor type worldwide, with hormone-responsive breast cancer the most common subtype. Despite the effectiveness of endocrine therapy, advanced disease forms represent an unmet clinical need. While drug combination therapies remain promising, differences in pharmacokinetic profiles result in suboptimal ratios of free drugs reaching tumors. We identified a synergistic combination of bisdemethoxycurcumin and exemestane through drug screening and rationally designed star -shaped poly-L-glutamic acid-based combination conjugates carrying these drugs conjugated through pH-responsive linkers for hormone-responsive breast cancer treatment. We synthesized/characterized single and combination conjugates with synergistic drug ratios/loadings. Physicochemical characterization/drug release kinetics studies suggested that lower drug loading prompted a less compact conjugate conformation that supported optimal release. Screening in monolayer and spheroid breast cancer cell cultures revealed that combination conjugates possessed enhanced cytotoxicity/synergism compared to physical mixtures of single-drug conjugates/free drugs; moreover, a combination conjugate with the lowest drug loading outperformed remaining conjugates. This candidate inhibited proliferation-associated signaling, reduced inflammatory chemokine/exosome levels, and promoted autophagy in spheroids; furthermore, it outperformed a physical mixture of single-drug conjugates/free drugs regarding cytotoxicity in patient-derived breast cancer organoids. Our findings highlight the importance of rational design and advanced in vitro models for the selection of polypeptide-based combination conjugates. [Display omitted] • Rational design and 3D breast cancer preclinical models support candidate selection. • Drug loading impacts release due to alterations in conjugate solution conformation. • Combination conjugates outperform physical mixtures of single-drug conjugates. • Screening in cancer organoids recapitulates advantages of combination conjugates. [ABSTRACT FROM AUTHOR]

Immunotherapy is a rapidly developing and effective strategy for cancer therapy. Among various immunotherapy approaches, peptides have garnered significant attention due to their potent immunomodulatory effects. In particular, melittin emerged as a promising candidate to enhance cancer immunotherapy by inducing immunogenic cell death, promoting the maturation of antigen-presenting cells, activating T cells, enhancing the infiltration and cytotoxicity of effector lymphocytes, and modulating macrophage phenotypes for relieving immunosuppression. However, the clinical application of melittin is limited by poor targeting and systemic toxicity. To overcome these challenges, melittin has been incorporated into biomaterials and related nanotechnologies, resulting in extended circulation time in vivo , improved targeting, reduced adverse effects, and enhanced anti-cancer immunological action. This review provides an in-depth analysis of the immunomodulatory effects of melittin-incorporated nanomedicines and examines their development and challenges for clinical cancer immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Four isomeric nitrosyl ruthenium complexes [RuCl(2mqn)(Val)(NO)] (1 – 4) were prepared (2mqn, 2-methyl-8-hydroxyquinoline; Val, l -valine) and characterized by 1H NMR, 13C NMR, absorption spectrum, electrospray ionization mass spectrometry, and X-ray crystal diffraction. Time-resolved FT-IR and fluorescence spectroscopy were used to monitor photo-induced NO release in solution, while NO released in living cells was imaged using a selective fluorescent probe. The isomeric complexes showed different levels of cytotoxicity against HeLa cells, and slightly photo-enhanced anti-proliferative activity was observed. The isomeric complexes 1 – 4 inhibited the growth of HeLa cells by inducing apoptosis and promoted cell cycle arrest in the S phase. Furthermore, they showed relatively lower cytotoxicity against the human liver cell line HL-7702. The different spatial configurations of the complexes is close related with the selective binding of the isomeric complexes with serum albumin, which provide insight into the potential applications of the nitrosyl ruthenium complexes. [Display omitted] • Nitrosyl ruthenium isomeric complexes were synthesized. • Photo-induced NO release was observed. • The cytotoxicity of the isomeric complexes was evaluated. • The interaction model with human serum albumin was determined. [ABSTRACT FROM AUTHOR]

The common carp is one of the most economically valuable freshwater fish worldwide and its aquaculture can be severely affected by the koi sleepy disease (KSD)/carp edema virus disease (CEVD). This study explores a natural outbreak of CEVD in a pond containing both clinically healthy and diseased fish of various origins exposed to the virus. We investigated mRNA expression of genes associated with known antiviral immune mechanisms, such as type I interferon signalling and cell‐mediated cytotoxicity, and performed a comprehensive protein expression analysis to highlight differences between the two groups in various organs. Significant differences in expression profiles of common carp with and without clinical signs were found to be strongly dependent on the organ from which the sample originated. Components of the complement cascade, including various C3 proteins, exhibited upregulation only in less affected organs, specifically the head kidney and spleen. Other complement proteins such as B/C2 and C9 showed upregulation in the kidney, spleen, and gills but not in the skin. Conversely, lysozymes C and G, were observed to be upregulated in the most affected organs of the skin and gills. This study submits the first description of the immune system related proteome using a mass spectrometry on the samples isolated from fish infected with CEV. It also offers a unique comparison of immune reaction of CEV infected and healthy fish under an infectious pressure. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells has shown promising results in early-phase clinical studies. However, advancing CAR-NK cell therapeutic efficacy is imperative. In this study, we investigated the impact of a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27 on NK-92 cells. We observed a significant improvement in NK-92 cell proliferation and cytotoxicity activity against B-cell cancer cell lines, both in vitro and in a xenograft mouse B-cell lymphoma model. Our systematic transcriptome analysis of the activated NK-92 CAR variants further supports the potential of IL-27 in fourth-generation CARs to overcome limitations of NK cell-based targeted tumor therapies by providing essential growth and activation signals. Integrating IL-27 into CAR-NK cells emerges as a promising strategy to enhance their therapeutic potential and elicit robust responses against cancer cells. These findings contribute substantially to the mounting evidence supporting the potential of fourth-generation CAR engineering in advancing NK cell-based immunotherapies. [Display omitted] [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells make only a small fraction of immune cells in the human body, however, play a pivotal role in the fight against cancer by the immune system. They are capable of eliminating abnormal cells via several direct or indirect cytotoxicity pathways in a self-regulating manner, which makes them a favorable choice as a cellular therapy against cancer. Additionally, allogeneic NK cells, unlike other lymphocytes, do not or only minimally cause graft-versus-host diseases opening the door for an off-the-shelf therapy. However, to date, the production of NK cells faces several difficulties, especially because the critical process parameters (CPPs) influencing the critical quality attributes (CQAs) are difficult to identify or correlate. There are numerous different cultivation platforms available, all with own characteristics, benefits and disadvantages that add further difficulty to define CPPs and relate them to CQAs. Our goal in this contribution was to summarize the current knowledge about NK cell expansion CPPs and CQAs, therefore we analyzed the available literature of both dynamic and static culture format experiments in a systematic manner. We present a list of the identified CQAs and CPPs and discuss the role of each CPP in the regulation of the CQAs. Furthermore, we could identify potential relationships between certain CPPs and CQAs. The findings based on this systematic literature research can be the foundation for meaningful experiments leading to better process understanding and eventually control. [ABSTRACT FROM AUTHOR]

• Antigen expression is heterogeneous in high-risk neuroblastoma. • sCAR-T cells show greater anti-tumor activity after SmAb stimulation. • Combination therapy successfully overcomes antigenic heterogeneity in high-risk neuroblastoma. Chimeric antigen receptor T (CAR-T) cells targeting single antigens show limited activity against solid tumors due to poor T cell persistence, low efficiency infiltration, and exhaustion together with heterogeneous tumor-associated antigen (TAA) expression. This is also true in high-risk neuroblastoma (HRNB), a lethal pediatric extracranial malignancy. To overcome these obstacles, a combinational strategy using GD2-specific and GPC2-specific CAR-T cells was developed to improve immunotherapeutic efficacy. We individually developed GD2-specific and GPC2-specific CARs containing a selective domain (sCAR) which was a peptide of 10 amino acids derived from human nuclear autoantigen La/SS-B. These constructs allowed us to generate two different HRNB antigen-specific CAR-T cells with enhanced biological activity through stimulating sCAR-engrafted T cells via a selective domain-specific monoclonal antibody (SmAb). Binding affinity and stimulation of GD2- and GPC2-specific sCARs by SmAb were measured, and transient and persistent anti-tumor cytotoxicity of GD2sCAR-T and GPC2sCAR-T cells were quantified in neuroblastoma cell lines expressing different TAA levels. The anti-tumor pharmaceutical effects and cellular mechanisms mediated by single or combinational sCAR-T cells were evaluated in vitro and in vivo. GD2- and GPC2-specific sCARs had antigen-specific binding affinity similar to their parental counterparts and were recognized by SmAb. SmAb-mediated stimulation selectively activated sCAR-T proliferation and increased central memory T cells in the final products. SmAb-stimulated sCAR-T cells had enhanced transient cytolytic activity, and combination therapy extended long-term anti-tumor activity in vitro through TNF-α and IL-15 release. Stimulated sCAR-T cells overcame heterogeneous antigen expression in HRNB, and the multi-TAA-targeting strategy was especially efficacious in vivo , inducing apoptosis through the caspase-3/PARP pathway and inhibiting the release of several tumor-promoting cytokines. These data suggest that combined targeting of multiple TAAs is a promising strategy to overcome heterogenous antigen expression in solid tumors and extend CAR-T cell persistence for HRNB immunotherapy. [ABSTRACT FROM AUTHOR]

In the fields of cultured meat, biopharmaceuticals, cell therapy, and tissue engineering, large numbers of mammalian cells are required; thus, highly-concentrated cell cultures are widely adopted. In general, such cultures can lead to cell damage caused by waste product accumulation and nutritional inadequacy. In this study, a novel co-culture system where the recombinant lactate-assimilating cyanobacterial strain, KC0110, derived from euryhaline Picosynechococcus sp. PCC 7002, and mammalian muscle cells cultured across porous membranes been developed. By using the KC0110 strain, the amount of ammonium and lactate excreted from C2C12 mouse muscle cells into the culture significantly decreased. Importantly, pyruvate and some amino acids, including pyruvate-derived amino acids, also increased significantly compared to those in monoculture of C2C12 cells. It is believed that the organic acids secreted by the KC0110 strain enhance the growth of mammalian cells, leading to a reduction in high-concentration culture-induced mammalian cell damage [lactate dehydrogenase (LDH) release] through cyanobacterial co-culture. These results show that, through co-cultivation with cyanobacteria, it is possible to culture mammalian cells, alleviating cell damage, even in highly-concentrated cultures. This study demonstrated an in vitro "symbiotic circular system" that can interchange metabolites produced by phototrophs and mammalian cells. [ABSTRACT FROM AUTHOR]

Minor ginsenosides produced by β-glucosidase are interesting biologically and pharmacologically. In this study, new ginsenoside-hydrolyzing glycosidase from Furfurilactobacillus rossiae DCYL3 was cloned and expressed in Escherichia coli strain BL21. The enzyme converted Rb1 and Gyp XVII into Rd and compound K following the pathways: Rb1→Rd and Gyp XVII→F2→CK, respectively at optimal condition: 40 °C, 15 min, and pH 6.0. Furthermore, we examined the cytotoxicity, NO production, ROS generation, and gene expression of Gynostemma extract (GE) and bioconverted Gynostemma extract (BGE) in vitro against A549 cell lines for human lung cancer and macrophage RAW 264.7 cells for antiinflammation, respectively. As a result, BGE demonstrated significantly greater toxicity than GE against lung cancer at a dose of 500 µg/mL but in normal cells showed lower toxicity. Then, we indicated an enhanced generation of ROS, which may be boosting cancer cell toxicity. By blocking the intrinsic way, BGE increased p53, Bax, Caspase 3, 9, and while Bcl2 is decreased. At 500 µg/mL, the BGE sample was less toxic in normal cells and decreased the LPS-treated NO and ROS level to reduce inflammation. In addition, BGE inhibited the expression of pro-inflammatory genes COX-2, iNOS, IL-6, and IL-8 in RAW 264.7 cells than the sample of GE. In conclusion, FrBGL3 has considerable downstream applications for high-yield, low-cost, effective manufacture of minor ginsenosides. Moreover, the study's findings imply that BGE would be potential materials for anti-cancer and anti-inflammatory agent after consideration of future studies. [ABSTRACT FROM AUTHOR]

The present study summarizes the current available literature regarding the viability of MCF7 breast cancer cells treated with gold (Au), silver (Ag) or zinc oxide (ZnO) nanoparticles at varying doses for 48 h. The data for this study were obtained from diverse research articles published between 2013 and 2023 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The evaluation focused on 20 PRISMA-compliant articles concerning MCF7 cells, yielding 137 outcome measures for meta-analysis. A generalized linear mixed model meta-analysis approach was employed to glean insights into the effects of novel nanoparticles on MCF7 breast cancer cells. The analysis covered a wide range of concentrations: Ag nanoparticles from 1.25 to 1,000 µg/ml, Au nanoparticles from 50 to 150 µg/ml, and ZnO nanoparticles from 1 to 1,000 µg/ml. Both intra-nanoparticle and inter-nanoparticle comparisons were conducted to detect differences. The findings showed that when concentrations reached or exceeded 60 µg/ml, considerable variation of cell viability was observed: Treatment with Ag nanoparticles resulted in cell viability ranging from 9 to 45%, ZnO nanoparticles resulted in cell viability ranging from 20 to 40%, and Au nanoparticles resulted in cell viability ranging from 3 to 58%. These findings indicated the signifi- cance of thoroughly exploring nanoparticle dosage to acquire a comprehensive understanding of their influence on cell viability. [ABSTRACT FROM AUTHOR]

The goal of this study is to investigate the antibacterial activity and sustained release of Centella Asiatica (CA) extract loaded in gelatin-based hydrogels, reinforced with MIL-53(Fe) (Fe-MOF) for the potential use as wound dressing. To induce antibacterial activity to the designed wound dressing, CA-extract was incorporated within the nanocomposite hydrogels. FT-IR analysis showed the distinctive peaks related to the Fe-MOF and CA-extract, with little shift, for hydrogel samples, which confirm the successful synthesis of nanocomposite hydrogels containing Fe-MOF and CA-extract. GC-mass analysis showed the antibacterial potential for CA-extract because of the presence of phenol, caryophyllene, and propanoic acid. SEM micrograph demonstrates the presence of Fe-MOF enhancing the porous of hydrogels. The antibacterial activity of prepared nanocomposite hydrogels was investigated by disk diffusion method revealing the significant inhibition zone growth for Basillus, Staphylococcus, and Streptococcus, as gram-positive and E. coli, Klebsiella, and P. aeruginosa as gram-negative bacteria and the "Candida albicans as fungi. Also, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by the micro-broth dilution method. The results showed that the nanocomposite hydrogel has a MIC values of 3.125 mg/ml and 6.25 mg/ml against both groups of bacteria. Cytotoxicity results obtained from MTT tests showed that the prepared hydrogels are biocompatible. The immunohistochemistry-stained hydrogel images revealed that the growth of cells on the CA-extract containing hydrogels was significantly increased in comparison to neat hydrogels. [ABSTRACT FROM AUTHOR]

The potential substitution of traditional cutting fluids with green Metalworking fluids (MWFs) is frequently explored because of their non-toxic and environmentally friendly characteristics. These green MWFs have often been evaluated for their tribological behavior and machining performance under various operating conditions. However, very few studies have analyzed the green metalworking fluids' ecological and eco-toxicological characteristics. With an aim to explore the potential impact and the related concerns of the developed green MWFs on the environment and eco-life, ecological and eco-toxicological experimental studies were performed in this research. This research study offers a comprehensive analysis of the biodegradability, soil eco-toxicity, cell viability, corrosion responsiveness, and reusability characteristics of the in-house developed nanoparticles-modified vegetable oil MWFs (MVO-MWFs). The findings from biodegradability studies demonstrate the inherent and readily biodegradable nature of the developed MWFs. Subsequently, soil eco-toxicity tests reveal the non-harmful nature of developed MWFs to the ecological organisms at the tested concentrations. Furthermore, during the cell viability assays, no evidence of cell death was observed in normal and cancer-affected cells under tested conditions. Additionally, the reusability studies on MQL imply that a considerable amount of MWF can be collected and reused to enhance the sustainability of the MWF system. This study established a decision-making approach to identify the optimal NP-based MWF combination by correlating multivariate data. Based on this work, a step-by-step methodology is recommended with four decision points to conduct a series of ecological and eco-toxicological protocols for the new or existing NP-based MWFs. This study contributes to the manufacturing research community and industry by shedding light on hitherto unexplored aspects of ecological and eco-toxicological investigations on the NP-based MVO-MWFs. [ABSTRACT FROM AUTHOR]

Eclipta prostrata is traditionally used in Asian medicine to treat skin diseases. Given the side effects and bacterial resistance of conventional treatments, especially in aging populations, alternative therapies are needed. This study assesses the antibacterial, antioxidant, and cytotoxic properties of E. prostrata extracts, focusing on optimizing extraction and fractionation methods for better efficacy. Dried whole plants were extracted with ethanol. Antibacterial activity was tested against Staphylococcus aureus, MRSA, S. epidermidis, and Pseudomonas aeruginosa using broth microdilution to determine minimum inhibitory concentrations (MIC). Antioxidant activity was assessed using a DPPH radical scavenging assay, and cytotoxicity was tested in Vero cells using an MTT assay. The MIC values for crude ethanol extracts ranged from 1.56 to 3.12 mg/ml, and from 0.78 to 1.56 mg/ml for fractionated compounds, indicating increased antibacterial efficacy in fractionated compounds. Antioxidant assays showed an IC50 of 0.666 mg/ml for crude extracts and 0.174 mg/ml for fractionated compounds, indicating higher antioxidant activity. Total phenolic content was 23.25±2.03 mg GAE/g for crude extracts and 95.56±1.09 mg GAE/g for fractionated compounds. Cytotoxicity assays showed IC50 values of 0.10±0.02 mg/ml for crude extracts and 0.06±0.01 mg/ml for fractionated compounds. This study advances extraction and fractionation methods, yielding extracts with significantly increased antibacterial and antioxidant properties. E. prostrata extracts, particularly fractionated compounds, show promising therapeutic potential, though high cytotoxicity in some fractions requires further investigation. These findings support the potential of E. prostrata in modern pharmaceutical formulations for treating skin conditions, especially those associated with aging. [ABSTRACT FROM AUTHOR]

Poly(vinyl alcohol) (PVA) based hydrogels have gained more interest in the field of biomaterials because of their many biomedical uses (i.e., wound healing, drug delivery, and tissue engineering) and intrinsic physicochemical and biological characteristics. They can be made using a variety of synthetic techniques, but all of them are very time-consuming. Among them, photopolymerization also referred to as light-induced polymerization, has drawn a lot of attention because of its benefits, which include not requiring the use of solvents, easy and quick network formation, energy efficiency, quick processing, control over both space and time and reliability of crosslinking density and matrix strength. Ultraviolet (UV)-curable hydrogels containing PVA as a main component are gaining interest because of their excellent properties, including biodegradability, biocompatibility, less cytotoxicity and remarkable mechanical strength. This review highlights the significance of UV curable systems and their components, types, advantages and disadvantages of photoinitiators (PIs), UV curable monomers and their structures, properties of UV-cured PVA hybrid hydrogels, and their characterizations and applications in different fields. The photopolymerization mechanisms, tunable properties, and unique advantages of these hydrogels have been explored in detail. Furthermore, it sheds light on recent advancements in PVA-based hydrogels research and future exploration in this domain. [ABSTRACT FROM AUTHOR]

An imine-based nanoscale COF has been synthesized and functionalized with a pyridone-derived structure to create a singlet oxygen-storing nanoplatform, which can continuously produce and release singlet oxygen to realize "afterglow" photodynamic therapy. [Display omitted] Photodynamic therapy (PDT) is an emerging treatment but often restricted by the availability of oxygen. Enhancing the lifespan of singlet oxygen (1O 2) by fractionated generation is an effective approach to improve the efficacy of PDT. Herein, an imine-based nanoscale COF (TpDa-COF) has been synthesized and functionalized with a pyridone-derived structure (Py) to create a 1O 2 -storing nanoplatform TpDa-COF@Py, which can reversibly capture and release 1O 2. Under 660 nm laser exposure, Py interacts with 1O 2 produced by the porphyrin motif in COF backbones to generate 1O 2 -enriched COF (TpDa-COF@Py + hv), followed by the release of 1O 2 through retro -Diels-Alder reactions at physiological temperatures. The continuous producing and releasing of 1O 2 upon laser exposure leads to an "afterglow" effect and a prolonged 1O 2 lifespan. In vitro cytotoxicity assays demonstrates that TpDa-COF@Py + hv exhibits an extremely low half-maximal inhibitory concentration (IC 50) of 0.54 µg/mL on 4T1 cells. Remarkably, the Py-mediated TpDa-COF@Py nanoplatform demonstrates enhanced cell-killing capability under laser exposure, attributed to the sustained 1O 2 cycling, compared to TpDa-COF alone. Further in vivo assessment highlights the potential of TpDa-COF@Py + hv as a promising strategy to enhance phototheronostics and achieve effective tumor regression. Accordingly, the study supplies a generalized 1O 2 "afterglow" nanoplatform to improve the effectiveness of PDT. [ABSTRACT FROM AUTHOR]

Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. Rhodiola, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from Rhodiola rosea, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of Rhodiola and salidroside against H2O2‐induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H2O2 for 4 h, and subsequently treated with Rhodiola or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin‐like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H2O2 (100 μM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with Rhodiola (12.5, 25, and 50 μg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H2O2‐induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R‐activated phosphorylation of ERK1/2, leading to the inhibition of Fas‐dependent proteins, HIF‐1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of Rhodiola and salidroside in H9c2 cells against oxidative damage. Our findings suggest that Rhodiola and salidroside possess antioxidative properties that mitigate H2O2‐induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose Rhodiola and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health. [ABSTRACT FROM AUTHOR]

Despite the therapeutic advances in treating malignancies, the efficient radiotherapeutic approaches with deprived adverse reactions still represent a potential clinical inquiry. The current study aims to elucidate the role of gallic acid (GA) in modifying the hazardous renal cytotoxicity induced by acute exposure to radiation. The MTT test was used to evaluate the viability of Vero cells exposed to 2 Gy gamma radiation with or without incubation of GA. In an in vivo model, male Wistar rats were divided into four experimental groups (n = 6): Control, Irradiated (IRR, 5 Gy), GA (100 mg/kg, i.p.) + IRR, and Glycogen synthase kinase inhibitor (GSKI, 3 mg/kg, i.p.) + IRR. Based on the MTT toxicity assay, from 0 and up to 5 μM dosages of GA did not demonstrate any cytotoxicity to Vero cells. The optimal GA dose that could protect the cells from radiation was 5 μM. Furthermore, GA exerted a protective effect from gamma radiation on renal tissue as indicated by corrected renal functions, decreased LDH level in serum, and balanced oxidative status, which is indicated by decreased tissue contents of NOx and TBARS with a significant increase of reduced GSH. These outcomes were inferred by the upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2) expression. The overall molecular impact of radiation in damaging the renal tissue may be explained by modifying the upstream AKT activity and its downstream targets GSK‐3β/Notch‐1. Here, we concluded that the anticipated adverse reaction in the course of radiation exposure could be protected by daily administration of GA. [ABSTRACT FROM AUTHOR]

Copyright of Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas is the property of Universidad de Santiago de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas is the property of Universidad de Santiago de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nickel and titanium (NiTi) based shape memory alloys (SMAs) are novel materials endowed with exceptional super-elasticity, corrosion resistance, and shape memory capabilities, making them well-suited for biomedical and industrial applications. The current study explores the impact of process parameters in powder mixed micro-electrical discharge milling (µ-EDM) on NiTi SMA, focusing on pulse on time (TON), voltage, pulse off time (TOFF), and RPM individually, employing a one factor at a time (OFAT) methodology to analyze surface characteristics, surface roughness (Ra), and material removal rate (MRR). The impact of black phosphorus powder combined with sesame oil (dielectric) on the surface of fabricated channels in commonly used biomaterials was investigated. The cytotoxicity test for biocompatibility was carried out to enhance the cell viability up to 79.89% after machining, which showed enhanced cell viability. The highest MRR the lowest Ra were obtained at the best input factors combination of 24 µs (TON), 6 µs (TOFF), 240 V, and 50 RPM tool rotation. Improved micro-channel quality was observed with lower TON, voltage, and RPM. [ABSTRACT FROM AUTHOR]

Isoflurane, a commonly used inhaled anesthetic, has been found to have a cardioprotective effect. However, the precise mechanisms have not been fully elucidated. Here, we found that isoflurane preconditioning enhanced OGD/R‐induced upregulation of miR‐210, a hypoxia‐responsive miRNA, in AC16 human myocardial cells. To further test the roles of miR‐210 in regulating the effects of isoflurane preconditioning on OGD/R‐induced cardiomyocyte injury, AC16 cells were transfected with anti‐miR‐210 or control anti‐miRNA. Results showed that isoflurane preconditioning attenuated OGD/R‐induced cardiomyocyte cytotoxicity (as assessed by cell viability, LDH and CK‐MB levels), which could be reversed by anti‐miR‐210. Isoflurane preconditioning also prevented OGD/R‐induced increase in apoptotic rate, caspase‐3 and caspase‐9 activities, and Bax level and decrease in Bcl‐2 expression level, while anti‐miR‐210 blocked these effects. We also found that anti‐miR‐210 prevented the inhibitory effects of isoflurane preconditioning on OGD/R‐induced decrease in adenosine triphosphate content; mitochondrial volume; citrate synthase activity; complex I, II, and IV activities; and p‐DRP1 and MFN2 expression. Besides, the expression of BNIP3, a reported direct target of miR‐210, was significantly decreased under hypoxia condition and could be regulated by isoflurane preconditioning. In addition, BNIP3 knockdown attenuated the effects of miR‐210 silencing on the cytoprotection of isoflurane preconditioning. These findings suggested that isoflurane preconditioning exerted protective effects against OGD/R‐induced cardiac cytotoxicity by regulating the miR‐210/BNIP3 axis. Isoflurane preconditioning elicited cardioprotection against OGD/R‐induced cardiomyocyte injury via maintaining mitochondrial function by regulating the miR‐210/BNIP3 axis. Our study provided new evidence for the underlying molecular mechanisms of protective effects of isoflurane preconditioning against OGD/R‐induced injury in cardiomyocytes. [ABSTRACT FROM AUTHOR]

Leaves of Stevia rebaudiana are rich source of sweet glycosides of steviol. The major glycoside, stevioside, diterpenoid glycoside--is used in India and various countries as a food sweetener for diabetic patients. Its medical use is also reported in various ailments like heart, liver, pancrease etc. Besides this it is also being used against obesity, stomach burn and to lower uric acid levels in blood. In present study the leaf extract with various extract were tested for immunomodulatry properties. We performed MTT assay to check the cell viability and cytotoxicity in peripheral blood mononuclear cell (PBMC) and also calculated the Trolox equivalent values to assess the antioxidant properties of Stevia rebaudiana.. Percent cell viability values of cells were found to be more than 50 percentages with increase in concentration. At higher dose all these extract showed significant inhibitory effects on proliferation. The aqueous extracts shown the maximum value of Trolox equivalent with 1:16 dilution. It means with the increase in the concentration of extract there is substantial increase in antioxidant property or we can assume antioxidant is dose dependent. But in same time cell viability gets reduced with increase in concentration. [ABSTRACT FROM AUTHOR]

The ecological threats of microplastics (MPs) have sparked research worldwide. However, changes in the topics of MP research over time and space have not been evaluated quantitatively, making it difficult to identify the next frontiers. Here, we apply topic modeling to assess global spatiotemporal dynamics of MP research. We identified nine leading topics in current MP research. Over time, MP research topics have switched from aquatic to terrestrial ecosystems, from distribution to fate, from ingestion to toxicology, and from physiological toxicity to cytotoxicity and genotoxicity. In most of the nine leading topics, a disproportionate amount of independent and collaborative research activity was conducted in and between a few developed countries which is detrimental to understanding the environmental fates of MPs in a global context. This review recognizes the urgent need for more attention to emerging topics in MP research, particularly in regions that are heavily impacted but currently overlooked. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Methods Results Conclusion To compare and evaluate the differences between EGCG and phosphatidylcholine‐encapsulated EGCG in terms of their anti‐inflammatory and antioxidant capacities.In this study, transdermal absorption experiments were conducted to compare the absorption capacity of EGCG and phosphatidylcholine‐encapsulated EGCG. Subsequently, the disparity in anti‐inflammatory and antioxidant efficacy between EGCG and phosphatidylcholine‐encapsulated EGCG were evaluated through cytotoxicity experiments, as well as the determination of cellular inflammatory factors and the measurement of ROS content under different treatment conditions.The concentration of EGCG, encapsulated in phosphatidylcholine, in porcine skin is 40.76 ± 1.29 μg/cm2, which is significantly higher than the concentration of EGCG alone (31.62 ± 2.01 μg/cm2). Also, the ability of phosphatidylcholine‐encapsulated EGCG to suppress inflammatory factors such as tumor necrosis factor‐α (TNF‐α), cyclooxygenase‐2 (COX‐2), and prostaglandin E2 (PGE2) was notably superior to that of EGCG alone. Both phosphatidylcholine‐encapsulated EGCG and EGCG showed excellent ROS scavenging ability in terms of antioxidant capacity.The percutaneous absorption and anti‐inflammatory impact of EGCG encapsulated within phosphatidylcholine were substantially enhanced when compared to EGCG by itself. Additionally, both formulations exhibited enhanced ROS scavenging capacities, albeit the variance between them was not pronounced. These insights furnish a vital theoretical underpinning for the utilization of phosphatidylcholine‐encapsulated EGCG in cosmetic applications, specifically for fostering products with anti‐inflammatory and antioxidant benefits. [ABSTRACT FROM AUTHOR]

Nanomaterial-mediated plant genetic engineering holds promise for developing new crop cultivars but can be hindered by nanomaterial toxicity to protoplasts. We present a fast, high-throughput method for assessing protoplast viability using resazurin, a non-toxic dye converted to highly fluorescent resorufin during respiration. Protoplasts isolated from hypocotyl canola (Brassica napus L.) were evaluated at varying temperatures (4, 10, 20, 30 ˚C) and time intervals (1–24 h). Optimal conditions for detecting protoplast viability were identified as 20,000 cells incubated with 40 µM resazurin at room temperature for 3 h. The assay was applied to evaluate the cytotoxicity of silver nanospheres, silica nanospheres, cholesteryl-butyrate nanoemulsion, and lipid nanoparticles. The cholesteryl-butyrate nanoemulsion and lipid nanoparticles exhibited toxicity across all tested concentrations (5-500 ng/ml), except at 5 ng/ml. Silver nanospheres were toxic across all tested concentrations (5-500 ng/ml) and sizes (20–100 nm), except for the larger size (100 nm) at 5 ng/ml. Silica nanospheres showed no toxicity at 5 ng/ml across all tested sizes (12–230 nm). Our results highlight that nanoparticle size and concentration significantly impact protoplast toxicity. Overall, the results showed that the resazurin assay is a precise, rapid, and scalable tool for screening nanomaterial cytotoxicity, enabling more accurate evaluations before using nanomaterials in genetic engineering. [ABSTRACT FROM AUTHOR]

Chronic graft rejection represents a significant threat to long-term graft survival. Early diagnosis, understanding of the immunological mechanisms and appropriate therapeutic management are essential to improve graft survival and quality of life for transplant patients. Knowing which immune cells are responsible for chronic vascular rejection would allow us to provide effective and appropriate treatment for these patients. It is now widely accepted that natural killer (NK) cells play an important role in chronic vascular rejection. They can either initiate chronic vascular rejection by recognizing missing self on the graft or be recruited by donor-specific antibodies to destroy the graft during antibody-mediated rejection.Whatever the mechanisms of activation of NK cells, they need to be primed to become fully activated and damaging to the graft. A better understanding of the signaling pathways involved in NK cell priming and activation would pave the way for the development of new therapeutic strategies to cure chronic vascular rejection. This review examines the critical role of NK cells in the complex context of chronic vascular rejection. [ABSTRACT FROM AUTHOR]

Quantum dots (QDs), also known as nanoparticle-based fluorescent probes, are luminescent semiconductor particles with a size range of 2-20 nm. The unique optical and electronic capabilities of QDs have led to expanded applications in several fields such as optoelectronics, transistors, sensors, photodetection, catalysis, and medicine. The distinct quantum effects of nanocrystals can be controlled by changing their sizes and shapes using a variety of top-down and bottom-up tactics. QDs were traditionally fabricated using complex, expensive, toxic, and aggressive chemical techniques, which limited their application in a variety of disciplines. A unique approach for the biosynthesis of nanomaterials has been devised, which employs living organisms in the synthesis process and adheres to green chemistry principles. Biogenic QDs have favorable physicochemical features, biocompatibility, and fewer cytotoxic effects as a result of using natural biomolecules and enzymatic processes for mineralization, detoxification, and nucleation of metals and nonmetals to synthesize QDs. This is the first comprehensive review of its kind that highlights the synthesis of several doped and undoped QDs, including graphene QDs, carbon dots, silicon QDs, N/S-CDs, silver-CDs, cadmium-selenium QDs, and zinc oxide QDs, exclusively using photoautotrophic algae and plants. The different plausible mechanisms behind phyco- and phyto-fabrication of QDs are also discussed in detail along with their applications that include detection of organic and inorganic compounds, degradation of hazardous dyes, free radical scavenging, antimicrobial activity, cytotoxicity and bioimaging. Thus, this review aims to give valuable insights for the rational fabrication of photoluminescent nanomaterials with tunable structural and functional properties. [ABSTRACT FROM AUTHOR]

Melittin is a bioactive peptide and the predominant component in bee venom (BV), studied for its many medical properties, such as antibacterial, anti-inflammatory, anti-arthritis, nerve damage reduction, and muscle cell regeneration. Melittin is primarily obtained through natural extraction and chemical synthesis; however, both methods have limitations and cannot be used for mass production. This study established a heterologous melittin expression system in the probiotic yeast Kluyveromyces marxianus. This yeast was selected for its advantages in stress tolerance and high secreted protein yields, simplifying purification. A > 95% high-purity melittin (MET) and its precursor promelittin (ProMET) were successfully produced and purified at 1.68 μg/mL and 3.33 μg/mL concentrations and verified through HPLC and mass spectrum. The functional test of the NSC-34 cell regeneration revealed that MET achieved the best activity compared to ProMET and the natural-extracted BV groups. Growth-related gene expressions were evaluated, including microtubule-associated protein 2 (MAP2), microtubule-associated protein Tau (MAPT), growth-associated protein 43 (GAP-43), choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), and acetylcholine esterase (AChE). The results indicated that treating MET increased MAP2, GAP-43, and VAChT expressions, in which cholinergic signaling is related to neurological functions. A heterologously expressed melittin in a probiotic yeast and its potential for promoting NSC-34 regeneration described here facilitate commercial and therapeutic use. Key points: • MET and its precursor ProMET were successfully hetero-expressed in K. marxianus • > 95% high-purity MET and ProMET were purified at 1.68 μg/mL and 3.33 μg/mL • MET has no cytotoxicity toward NSC-34 and significantly promotes NSC-34 growth [ABSTRACT FROM AUTHOR]

Novel nanoprism-shaped manganese-doped copper sulfide (Mn–CuS) was fabricated by two-phase colloidal method (Mn percentages = 0%, 1%, 3%, and 5%). The Mn–CuS was analyzed by XRD, FTIR, UV–Vis spectrometer, and TEM. The XRD shows that the hexagonal covellite copper sulfide peaks appeared at 2θ=47.9∘,31.9∘,47.8∘, and 31.8∘ for 0%, 1%, 3%, and 5% respectively, and orthorhombic chalcocite copper sulfide appeared at the peaks that are corresponding the planes (412), (275), (029) and (106). According to UV–Vis analysis, the optical absorption of manganese-doped copper sulfide 0%, 1%, 3%, and 5% clearly appeared in the UV–Vis region at 518, 440, 478, and 477nm respectively, and there are broad peaks for localized surface plasmon resonances (LSPR) of CuS located at 970, 1061, 1002, and 1006nm for Mn–CuS 0%, 1%, 3%, and 5%, respectively. The favored nanoprism-shaped sample (manganese-doped copper sulfide 1%) was coated with gum Arabic (GA) in order to decrease the cytotoxicity and enhance the biocompatibility. The antibacterial activity of manganese-doped copper sulfide and GA@Mn–CuS 1% nanostructure toward Staphylococcus aureus and Escherichia coli bacteria was determined by inhibition zone. It was found that the fabrecated Mn–CuS 1% nanoprisms were more active toward both E. coli and S. aureus bacteria and the doping enhanced the antibacterial activity. [ABSTRACT FROM AUTHOR]

ABSTRACT In recent years, significant attention has been given to the strategy of linking novel active molecules with different biological targets and antitumor mechanisms to the axial positions of Pt(IV) complexes, aiming to synthesize new Pt(IV) antitumor complexes with excellent properties. In this study, Satraplatin analogs and the highly lipophilic bioactive molecule cannabidiol (CBD) were chosen as the main research subjects. By combining these two and introducing other bioactive small molecules, we aimed to enrich the functionalities of Pt(IV) antitumor complexes. Five new multifunctional Pt(IV) antitumor complexes, P1–P5, were prepared. All Pt(IV) prodrugs demonstrated antitumor effects in various tumor cell lines. Notably, compound P1 exhibited significant inhibitory effects, with half‐maximal inhibitory concentration (IC50) values that were 2.1, 1.5, and 1.3 times higher than those of satraplatin in HCT‐116, A549, and HeLa cell lines, respectively, and 2.4, 1.5, and 2.0 times higher than those of the combination of satraplatin and CBD. The cytotoxicity of P1 toward cancer cell lines is significantly higher than that of the combination therapy group, providing preliminary evidence that the strategy of combining CBD and platinum‐based antitumor drugs into a complex is highly effective in simultaneously enhancing the cytotoxicity of both, resulting in a good synergistic antitumor effect. Further research shows that after treating cells with P1, the induced ROS generation increases in a dose‐dependent manner, disrupting the cell's redox homeostasis, leading to oxidative stress, and ultimately causing cell apoptosis. This strategy of introducing the bioactive molecule CBD into platinum‐based drug formation complexes to improve efficacy has been shown to be feasible and deserves further study. [ABSTRACT FROM AUTHOR]