The revealing of the Cyto-genotoxic properties (Allium and MTT) and the effect of chicken meat quality of characterized zein-eugenol nanofibers.

Electrospun zein-based eugenol nanofibers (ZEnF) with diameters (148.19-631.52 nm) were fabricated. Thermal degradation was found as <15 % until 300 °C while the nanofiber diffraction pattern presented three main peaks among the 5o and 45o positions. ZEnF was not only evaluated as non-toxic to cells but also possessed anticancer characteristics revealing with the MCF-7 cell line at 800 µg/mL (reduction: 18.08 %) and 1600 µg/mL (reduction: 41.64 %). Allium tests revealed that ZEnF did not have any adverse impact on the health status (chromosomes-DNA) of exposed organisms. Following the nanofiber coating for chicken meat parts (thigh and breast), it was observed up to 1.25 log CFU/g limitation in total viable bacteria counts (p < 0.05). The sensory score (difference: 3.64 in 10 points scoring on the 6th day of the cold storage) and odor score of chicken meat samples were found to be as higher than control samples (p < 0.05).

Critical new insights into the interactions of hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) with albumin at molecular and cellular levels.

A key characteristic to be elucidated, to address the harmful health risks of environmental perfluorinated alkyl substances (PFAS), is their binding modes to serum albumin, the most abundant protein in blood. Hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) is a new industrial replacement for the widespread linear long-chain PFAS. However, the detailed interaction of new-generation short-chain PFAS with albumin is still lacking. Herein, the binding characteristics of bovine serum albumin (BSA) to GenX were explored at the molecular and cellular levels. It was found that this branched short-chain GenX could bind to BSA with affinity lower than that of legacy linear long-chain perfluorooctanoic acid (PFOA). Site marker competitive study and molecular docking simulation revealed that GenX interacted with subdomain IIIA to form BSA-GenX complex. Consistent with its weaker affinity to albumin protein, the cytotoxicity of branched short-chain GenX was less susceptible to BSA binding compared with that of the linear long-chain PFOA. In contrast to the significant effects of strong BSA-PFOA interaction, the weak affinity of BSA-GenX binding did not influence the structure of protein and the cytotoxicity of GenX. The detailed characterization and direct comparisons of serum albumin interaction with new generation short-chain GenX will provide a better understanding for the toxicological properties of this new alternative.

Design, Synthesis, and Anticancer and Antibacterial Activities of Quinoline-5-Sulfonamides.

A series of new unique acetylene derivatives of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonamide 3a-f and 6a-f were prepared by reactions of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonyl chlorides with acetylene derivatives of amine. A series of new hybrid systems containing quinoline and 1,2,3-triazole systems 7a-h were obtained by reactions of acetylene derivatives of quinoline-5-sulfonamide 6a-d with organic azides. The structures of the obtained compounds were confirmed by 1H and 13C NMR spectroscopy and HR-MS spectrometry. The obtained quinoline derivatives 3a-f and 6a-f and 1,2,3-triazole derivatives 7a-h were tested for their anticancer and antimicrobial activity. Human amelanotic melanoma cells (C-32), human breast adenocarcinoma cells (MDA-MB-231), and human lung adenocarcinoma cells (A549) were selected as tested cancer lines, while cytotoxicity was investigated on normal human dermal fibroblasts (HFF-1). All the compounds were also tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis. Only the acetylene derivatives of 8-hydroxyquinoline-5-sulfonamide 3a-f were shown to be biologically active, and 8-hydroxy-N-methyl-N-(prop-2-yn-1-yl)quinoline-5-sulfonamide (3c) showed the highest activity against all three cancer lines and MRSA isolates. Its efficacies were comparable to those of cisplatin/doxorubicin and oxacillin/ciprofloxacin. In the non-cancer HFF-1 line, the compound showed no toxicity up to an IC50 of 100 µM. In additional tests, compound 3c decreased the expression of H3, increased the transcriptional activity of cell cycle regulators (P53 and P21 proteins), and altered the expression of BCL-2 and BAX genes in all cancer lines. The unsubstituted phenolic group at position 8 of the quinoline is the key structural fragment necessary for biological activity.

Novel Insights into the Biological Activity of Croton lechleri Twigs Extracts and Advancements in Their Sustainable Recovery.

Sangre de drago, the sap of Croton lechleri Müll. Arg. tree, has been used for centuries in traditional medicine owing to its diverse biological activities. Extracts derived from different parts of the species contain a multitude of phytochemicals with varied applications. Twigs, however, are among the least studied parts of the plant. This study unveils new biological activities of Croton lechleri twig extracts recovered by applying Soxhlet and advanced green techniques. For all extracts, total phenolic content and antioxidant activity were determined. Subsequently, four were selected, and their cytotoxic effects were assessed on both normal (HaCat) and malignant melanoma (A375) skin cell lines using the MTT assay and trypan blue exclusion assay. All showed dose-dependent cytotoxicity, with the Soxhlet ethanol extract demonstrating the highest selectivity towards A375 cells over HaCat cells. The extracts induced apoptosis and necrosis, as confirmed by Annexin V/PI dual-labeling and flow cytometry, highlighting their ability to trigger programmed cell death in cancer cells. The selective inhibition of cell cycle progression in A375 compared to HaCat observed both for Soxhlet ethanol and pressurized ethanol extracts induces cell cycle arrest at multiple points, primarily in the G1 and G2/M phases, and significantly reduces DNA synthesis as evidenced by the decrease in the S-phase population, confirmed by the EdU assay. Consequently, the Soxhlet extract composition was analyzed using LC-MS, which revealed their richness in polyphenolic compounds, particularly flavonoids from the flavonol subclass.

Synthesis and evaluation of in vitro antioxidant, anticancer, and antibacterial properties of new benzylideneiminophenylthiazole analogues.

A series of new benzylideneiminophenylthiazole analogues were designed and synthesized. Common spectroscopic methods, such as FT-IR, 1H-, 13C-NMR, and MASS spectra, and elemental analysis, were used to confirm the molecular structures. Then, the antioxidant, cytotoxicity, and anti-bacterial effects of synthesized analogues were assessed against 2,2-diphenyl-1-picrylhydrazyl (DPPH), three cancer cell lines, and two bacterial strains, respectively. Among the analogues, 7f was detected as the most potent compound for antioxidant activity. Moreover, the compounds 7b, 7f, and 7 g exhibited the maximum cytotoxicity activity against MCF-7, HepG-2, and A549 cell lines, respectively. Finally, 7e showed the highest anti-bacterial activity against both S. aureus and E. coli strains. It was concluded from the antioxidant, cytotoxicity, and anti-bacterial effects that the benzylideneiminophenylthiazoles might serve as candidate molecules for the development of small molecules with medicinal potential.

NKG2D (Natural Killer Group 2, Member D) ligand expression and ameloblastoma recurrence: a retrospective immunohistological pilot study.

BACKGROUND/PURPOSE: This retrospective immunohistological pilot study aimed to investigate the influence of natural killer group 2, member D (NKG2D) ligand expression on ameloblastoma recurrence after surgical resection. It also aimed to elucidate additional clinical factors that could serve as predictors of ameloblastoma recurrence. MATERIALS AND METHODS: This study included 96 patients who were histologically diagnosed with ameloblastoma after surgical resection. The expression of NKG2D ligands, including UL16-binding proteins (ULBPs) 1-3 and major histocompatibility complex class I chain-related molecule (MIC) A/B, was evaluated in formalin-fixed paraffin-embedded tumor tissues via immunohistochemistry assays. Furthermore, the patients' electronic medical records were reviewed. Multivariate Cox regression analysis was conducted, and data were expressed as adjusted hazard ratios [HRs] with 95% confidence intervals [95% CIs]. RESULTS: Multivariate analysis revealed that recurrent tumors (ref.: primary; adjusted HR [95% CI]: 2.780 [1.136, 6.803], p = 0.025) and positive MICA/B expression (ref.: negative; adjusted HR [95% CI]: 0.223 [0.050, 0.989], p = 0.048) independently affected recurrence-free survival in ameloblastoma. CONCLUSION: This study identified recurrent cases and loss of MICA/B expression as independent predictors of early ameloblastoma recurrence following surgical resection. The findings suggest that decreased MICA/B expression might undermine NKG2D-mediated tumor immunosurveillance, thereby influencing early recurrence.

Toxicity of Dibutyl phthalate (DBP) toward isolated human blood lymphocytes: Apoptosis initiated from intracellular calcium enhancement and mitochondrial/lysosomal cross talk.

Dibutyl phthalate (DBP) is a phthalate ester with wide application in industrial products, so human exposure can happen in workplaces and environment. Conflicting results have been acquired in researches which measured the influences of phthalates contact on immune responses in laboratory animals. Nevertheless, the straight influence of DBP on human lymphocytes and entire mechanisms of its effect against these cells continue to be unexplored. The major purpose of present research was to evaluate the mechanisms which lead to the DBP toxicity on human lymphocytes using accelerated cytotoxicity mechanisms screening (ACMS) technique. Cell viability was determined following12h incubation of lymphocytes with 0.05-1 mM DBP, and mechanistic parameters were assessed after 2, 4 and 6 h of lymphocyte treatment with ½ the IC5012h (0.3 mM), the IC5012h (0.6 mM) and twice the IC5012h (1.2 mM) of DBP. The IC5012 h of a chemical/toxicant is defined as concentration that kills 50 % of cells after 12 h of exposure. The results indicate that DBP exerts toxic effects on isolated human lymphocytes, probably through mitochondrial and lysosomal damage induced by glutathione depletion and oxidative stress. In this study, suppression of cytokines (IL2, INF-gamma and TNF-alpha) production and increase in intracellular calcium were also related to DBP induced lymphocyte toxicity.

Synthesis and characterization of new hexahydroquinoline derivatives and evaluation of their cytotoxicity, intracellular ROS production, and inhibitory effects on inflammatory mediators.

Inflammation is a response to injury and infection in an organism. It can be categorized as acute or chronic. Chronic inflammation is the underlying cause of many diseases such as Alzheimer disease, diabetes, rheumatoid arthritis, atherosclerosis, and cardiovascular diseases. Recent studies have proven the antiinflammatory properties of 1,4-dihydropyridines (1,4-DHPs) and their derivatives, which have many biological activities including the blocking of calcium channels. In this study, 15 compounds that are condensed derivatives of 1,4-DHPs, with the general structure of hexahydroquinoline-3-carboxylate, were synthesized. These compounds, expected to show inhibitory activity against inflammatory mediators, were obtained by the reaction of 4-(difluoromethoxy)benzaldehyde, substituted/nonsubstituted 1,3-cyclohexanedione derivatives, and appropriate alkyl acetoacetate compounds in the presence of ammonium acetate as a nitrogen source according to the Hantzsch synthesis method. The structures of the synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, and HRMS methods. The cytotoxic properties of the compounds were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method in the 3T3 cell line. Among the 15 compounds, the three compounds with the lowest levels of cytotoxic effects were selected for further experiments. Inflammation was induced by lipoxygenase and the effects of the selected compounds on the levels of reactive oxygen species, cytokines, and complement C3 and C9 regulatory proteins were investigated. It was found that the three selected compounds decreased the levels of transforming growth factor-beta 1 (TGF-ß1). Among these compounds, compound 3e provided the most significant decrease in this cytokine. Moreover, 3e increased both C3 and C9 levels. Molecular modeling studies also showed that 3e had better affinity for TGF-ß1. When the binding modes of these compounds in the active site of TGF-ß1 were analyzed, it was found that compound 3e had hydrophobic interactions with amino acids Leu142, Tyr84, and Ile13; halogen bond interactions with Asp92; and hydrogen bond interactions with Ser89, Gly88, and Gly14 in the active binding site. Further in vitro and in vivo studies are needed to show the possible mechanism of action of compound 3e.

Cytotoxicity and mechanisms of perfluorobutane sulfonate (PFBS) in umbilical cord fibroblast cells of Yangtze finless porpoise.

Yangtze finless porpoises (YFP) accumulate high levels of per- and polyfluoroalkyl substances (PFASs). However, the health impacts of PFASs to YFP are still unknown because it is technically and ethically unfeasible to use the critically endangered YFP in toxicological exposures. To uncover the potential toxicities of PFASs to YFP, this study exposed a YFP umbilical cord fibroblast cell line to perfluorobutane sulfonate (PFBS), an emerging PFASs pollutant in the aquatic environments. After exposure, the cytotoxicity and mechanisms of PFBS were explored. Our preliminary experiments found that PFBS compromised the cell viability in a concentration and duration dependent manner. In an exposure of 48-h duration, the maximum no observed effect concentration (NOEC) of PFBS was determined to be 400 µM. High-throughput proteomics were then conducted to identify the differentially expressed proteins in YFP cells exposed to 400 µM PFBS for 48 h. The results found that PFBS exposure significantly perturbed the proteome fingerprints of YFP umbilical cord fibroblast cells. Functional annotation of differential proteins showed that PFBS had the potential to impair a variety of biological processes associated with the immunity, oxidative stress, metabolism, and proteolysis. Consistently, the intracellular levels of reactive oxygen species (ROS) and proinflammatory cytokine IL-1ß were significantly increased by PFBS in YFP umbilical cord fibroblast cells. Overall, this study highlights the toxic effects of emerging PFASs on YFP and provides reference data to evaluate the health risks of aquatic pollution under the context of national YFP protection. To our knowledge, this is the first omics study using YFP umbilical cord fibroblast cells in ecotoxicology of PFASs, which is applicable to various cetacean species and pollutants.

Synthesis and antiproliferative activity of cisplatin-3-chloropiperidine conjugates.

We report the synthesis and characterization of two novel cisplatin- alkylating agents conjugates. Combining a platinum based cytostatic agent with a sterically demanding alkylating agent could potentially induce further DNA damage, block cell repair mechanisms and keep the substrate active against resistant tumor cell lines. The 3-chloropiperidines utilized as ligands in this work are cyclic representatives of the N-mustard family and were not able to coordinate platinum on their own. The introduction of a second coordination site, in form of a pyridine moiety, led to the isolation of the desired conjugates. They were characterized with HRMS, CHN-analyses and XRD. We concluded this work by examining the cytotoxicity of the ligands and the obtained complexes with MTT assays in human cancer cell lines. While the ligands showed hardly any activity, the novel conjugates both displayed a high antiproliferative and cytotoxic potency in a panel of three cell lines. Moreover, both complexes were able to largely circumvent the acquired cisplatin resistance of A2780cisR ovarian cancer cells, both in the MTT assay and a flow-cytometric apoptosis assay.

Synthesis of New Chromen-5-one Derivatives from Dimedone and their Antiproliferative Evaluations against Selected Cancer Cell Lines Together with Hepatocellular Carcinoma and Cervical Carcinoma.

BACKGROUND: The coumarin nuclei, which exist in many heterocyclic compounds, has gained a lot of attention over the past decade due to their wide range of biological activities such as antibacterial, anticoagulant, antiviral, antifungal, anticancer, and anti-inflammatory properties. OBJECTIVE: The multi-component reactions of 5,5-dimethylcyclohexane-1,3-dione with acetophenone derivatives and triethoxymethane produced biologically active target chromene molecules and their fused derivatives. METHODS: The reaction of 5,5-dimethylcyclohexane-1,3-dione and each of triethoxymethane and acetophenone derivatives 3a-g in absolute ethanol containing triethylamine gave the 4,6,7,8-tetrahydro-5H-chromen-5-one derivatives 4a-g. Compounds 4a-d were used for further heterocyclization reactions to produce biologically active fused pyrazole, thiophene, and thiazole derivative corporate with the chromenes caffold. RESULTS: The cytotoxicity of the synthesized compounds were evaluated using six cancer cell lines together with c-Met kinase and PC-3 cell line inhibitions. In addition, cytotoxicity toward hepatocellular carcinoma HepG2 and cervical carcinoma HeLa was carried out as well as the in-vitro cytotoxic potential for all compounds against peripheral blood lymphocytes (PBL) extracted from healthy donors. Morphological changes of the A549 cell line by the two most active compounds were also studied. CONCLUSION: The synthesized heterocyclic compounds were originally obtained from 5,5-dimethylcyclohexane1,3-dione. Several of the produced compounds exhibited high inhibitions toward several cancer cell lines proving high inhibitions, therefore, encouraging further studies to synthesize heterocyclic compounds based on chromene scaffold.

Feeder cell training shapes the phenotype and function of in vitro expanded natural killer cells.

Natural killer (NK) cells are candidates for adoptive cell therapy, and the protocols for their activation and expansion profoundly influence their function and fate. The complexity of NK cell origin and feeder cell cues impacts the heterogeneity of expanded NK (eNK) cells. To explore this, we compared the phenotype and function of peripheral blood-derived NK (PB-NK) and umbilical cord blood-derived NK (UCB-NK) cells activated by common feeder cell lines, including K562, PLH, and 221.AEH. After first encounter, most PB-NK cells showed degranulation independently of cytokines production. Meanwhile, most UCB-NK cells did both. We observed that each feeder cell line uniquely influenced the activation, expansion, and ultimate fate of PB eNK and UCB eNK cells, determining whether they became cytokine producers or killer cells. In addition, they also affected the functional performance of NK cell subsets after expansion, that is, expanded conventional NK (ecNK) and expanded FcRγ- NK (eg-NK) cells. Hence, the regulation of eNK cell function largely depends on the NK cell source and the chosen expansion system. These results underscore the significance of selecting feeder cells for NK cell expansion from various sources, notably for customized adoptive cell therapies to yield cytokine-producing or cytotoxic eNK cells.

Chemical Profiling and Antioxidant, Anti-Inflammatory, Cytotoxic, Analgesic, and Antidiarrheal Activities from the Seeds of Commonly Available Red Grape (Vitis vinifera L.).

Objectives: The current study aimed to conduct a phytochemical screening of commonly known fruit red grape (Vitis vinifera L.) seed methanolic extract through gas chromatography and mass spectrometry (GC-MS) to identify the bioactive compounds responsible for its health benefits and evaluate the pharmacological potentialities of the extract and its fractions against oxidation, inflammation, pain, and diarrhea. Methods: The in vitro antioxidant, anti-inflammatory, and cytotoxic characteristics of methanolic extracts and various solvent fractions of V. vinifera were evaluated using the DPPH free radical scavenging assay, membrane stabilizing, and brine shrimp lethality bioassay. Furthermore, the study assessed the effects of crude extracts (200, 400, and 600 mg/kg of body weight) on pain relief and reduction of diarrhea in animals using methods such as tail immersion, the acetic acid-induced writhing technique, and a diarrheal mouse model induced with castor oil. Results: A total of 73 phytoconstituents were predominantly found in the seed extract based on the GC-MS analysis. Among the identified compounds, 9-octadecenamide (13.7%), and (9E,11E)-octadeca-9,11-dienoate (11.07%) are most abundant. Several notable constituents, such as gamma-sitosterol, stigmasterol, paromomycin, 4,6-cholestadienol, gamma-tocotrienol, 24-Propylidenecholest-5-en-3beta-ol, and alpha-tocopherol acetate, are also present. The methanolic extract of V. vinifera seed and its different solvent fractions showed promising antioxidant properties (IC50 = 1.19-17.42 µg/mL) compared to the standard antioxidant butylated hydroxytoluene (IC50 = 20.46 µg/mL). Aqueous soluble fraction exerted inhibition of nearly 50% heat-induced hemolysis compared to the standard acetylsalicylic acid (42%). Besides, all the tested doses (200, 400, and 600 mg/kg bw) of the crude extract showed significant (P < .05) analgesic and antidiarrheal effects. Conclusion: The current findings endorsed the health benefits of V. vinifera by revealing potent antioxidant, anti-inflammatory, analgesic, and antidiarrheal effects. Nevertheless, further in-depth analysis of the plant's chemical constituents and pharmacological effects on health is warranted for novel drug discovery from V. vinifera.

Drug response-based precision therapeutic selection for tamoxifen-resistant triple-positive breast cancer.

Breast cancer adaptability to the drug environment reduces the chemotherapeutic response and facilitates acquired drug resistance. Cancer-specific therapeutics can be more effective against advanced-stage cancer than standard chemotherapeutics. To extend the paradigm of cancer-specific therapeutics, clinically relevant acquired tamoxifen-resistant MCF-7 proteome was deconstructed to identify possible druggable targets (N = 150). Twenty-eight drug inhibitors were used against identified druggable targets to suppress non-resistant (NC) and resistant cells (RC). First, selected drugs were screened using growth-inhibitory response against NC and RC. Seven drugs were shortlisted for their time-dependent (10-12 days) cytotoxic effect and further narrowed to three effective drugs (e.g., cisplatin, doxorubicin, and hydroxychloroquine). The growth-suppressive effectiveness of selected drugs was validated in the complex spheroid model (progressive and regressive). In the progressive model, doxorubicin (RC: 83.64 %, NC: 54.81 %), followed by cisplatin (RC: 76.66 %, NC: 68.94 %) and hydroxychloroquine (RC: 68.70 %, NC: 61.78 %) showed a significant growth-suppressive effect. However, in fully grown regressive spheroid, after 4th drug treatment, cisplatin significantly suppressed RC (84.79 %) and NC (40.21 %), while doxorubicin and hydroxychloroquine significantly suppressed only RC (76.09 and 76.34 %). Our in-depth investigation effectively integrated the expression data with the cancer-specific therapeutic investigation. Furthermore, our three-step sequential drug-screening approach unbiasedly identified cisplatin, doxorubicin, and hydroxychloroquine as an efficacious drug to target heterogeneous cancer cell populations. SIGNIFICANCE STATEMENT: Hormonal-positive BC grows slowly, and hormonal-inhibitors effectively suppress the oncogenesis. However, development of drug-resistance not only reduces the drug-response but also increases the chance of BC aggressiveness. Further, alternative chemotherapeutics are widely used to control advanced-stage BC. In contrast, we hypothesized that, compared to standard chemotherapeutics, cancer-specific drugs can be more effective against resistant-cancer. Although cancer-specific treatment identification is an uphill battle, our work shows proteome data can be used for drug selection. We identified multiple druggable targets and, using ex-vivo methods narrowed multiple drugs to disease-condition-specific therapeutics. We consider that our investigation successfully interconnected the expression data with the functional disease-specific therapeutic investigation and selected drugs can be used for effective resistant treatment with higher therapeutic response.

Epidemiology, Pathophysiology, and Current Treatment Strategies in Stroke.

Both ischemic and hemorrhagic strokes are critical health issues and the incidence is on the rise. The rapid neurological degeneration that can occur with either type of stroke warrants prompt medical attention. In the article, we critically reviewed the literature examining their incidence, pathophysiology, and present treatment strategies. Clinical trials show conflicting findings, with ischemic strokes accounting for 87% of all strokes. Brain injury following an ischemic stroke results in cell death and necrosis, immune cells being the primary actors in the process of neuroinflammation. In order to develop neuroprotective drugs against ischemic stroke, detailed investigation of glutamate production and metabolism as well as downstream pathways controlled by glutamate receptors provides significant information on the underlying mechanisms. The permeability of the blood-brain barrier and the degradation of glutamine synthase are two potential mechanisms by which peritoneal dialysis accelerates brain-to-blood glutamate clearance and thus reduces glutamate levels in the brain after a stroke. Oxidative stress in an ischemic stroke disturbs the oxidant-antioxidant balance, which is particularly problematic for brain cells that are high in polyunsaturated fatty acids. Because of demographic factors like age, sex, race/ethnicity, and socioeconomic status, the incidence and prevalence of stroke differ across people and regions. For rapid diagnosis and treatment decisions, diagnostic imaging tools such as vascular imaging, CT, and MRI are essential. To aid in the recovery and lessen neurological impairments following a stroke, novel avenues of research are under investigation on neuroprotective medications that target inflammation, oxidative stress, and neuronal death.

Synthesis, antimicrobial activity, and mechanistic studies of enterocin DD14, a leaderless two-peptide bacteriocin.

Bacteriocins are promising alternatives to antibiotics in the food, veterinary and medical sectors, but their study and use is often hampered by the low yields and high costs associated with their purification from naturally occurring bacteria. Chemical synthesis has emerged as a means to overcome this limitation and design more active variants. In this study, microwave-assisted solid-phase peptide synthesis was used to produce the leaderless two-peptide bacteriocin enterocin DD14 (EntDD14), composed of EntDD14A (44 amino acids) and EntDD14B (43 amino acids). The resulting synthetic peptides, syn-EntDD14A and syn-EntDD14B, were tested against Gram-positive bacteria including Listeria, Staphylococcus and Enterococcus strains. Both peptides were found to be necessary for optimal, but not synergistic, antibacterial activity and to act through a pore-forming mechanism. Both peptides exhibited moderate cytotoxicity against eukaryotic cells.

Citral: A potent inhibitor of advanced glycation end products.

Advanced glycation end products (AGEs), which are produced during food processing, pose health risks to humans. This study found that citral (Cit) effectively inhibited the formation of both fluorescent and non-fluorescent AGEs in the bovine serum albumin (BSA)-glucose (Glc) system. Cit achieved an average inhibition rate of over 80 % for fluorescent AGEs and reduced the levels of N-ε-carboxymethyllysine (CML) and N-ε-carboxyethyllysine (CEL) by up to 45.85 % and 59.32 %, respectively. The comprehensive characterizations and high-resolution mass spectrometry analysis demonstrated that the carbonyl group and CC group present on Cit could compete with Glc for the amino groups on BSA, thereby reducing the formation of AGEs. Additionally, the cytotoxicity assay demonstrated that the BSA-Cit adducts were non-toxic. This research indicated that Cit was a potent and safe inhibitor of AGEs.

The role of Drp1 - Pink1 - Parkin - mediated mitophagy in perfluorobutane sulfonate- induced hepatocyte damage.

Perfluorobutane sulfonate (PFBS) is recognized as a highly persistent environmental contaminant, notorious for its chemical stability and enduring presence in ecosystems. Its propensity for persistence and environmental mobility allows PFBS to infiltrate the human body, predominantly accumulating in the liver where it poses a potential risk for hepatic damage. This investigation aimed to explore the outcomes of PFBS on the physiological functionalities of hepatocytes in vitro. To this end, hepatocytes were exposed to 750 ug/ml PFBS, followed by an analysis of various cellular phenotypes and functionalities, including assessments of cell viability and mitochondrial integrity. The findings indicated that PFBS exposure led to a suppression of cell proliferation and an increase in apoptotic cell death. Moreover, PFBS exposure was found to augment the generation of reactive oxygen species (ROS) and induce significant mitochondrial dysfunction. Gene expression analysis identified significant changes in genes associated with numerous tumor signaling pathways and autophagy signaling pathways. Further examinations revealed an increase in cellular mitophagy following PFBS exposure, coupled with the activation of the mitophagy-associated Drp1/Pink1/Parkin pathway. Inhibition of mitophagy was observed to concurrently amplify cellular damage and inhibit the Drp1/Pink1/Parkin pathway. Together, these findings highlight PFBS's capacity to inflict hepatocyte injury through mitochondrial disruption, positioning Drp1/Pink1/Parkin-mediated mitophagy as a crucial cellular defense mechanism against PFBS-induced toxicity.

Novel thiazole-based cyanoacrylamide derivatives: DNA cleavage, DNA/BSA binding properties and their anticancer behaviour against colon and breast cancer cells.

A novel series of 2-cyano-3-(pyrazol-4-yl)-N-(thiazol-2-yl)acrylamide derivatives (3a-f) were synthesized using Knoevenagel condensation and characterized using various spectral tools. The weak nuclease activity of compounds (3a-f) against pBR322 plasmid DNA was greatly enhanced by irradiation at 365 nm. Compounds 3b and 3c, incorporating thienyl and pyridyl moieties, respectively, exhibited the utmost nuclease activity in degrading pBR322 plasmid DNA through singlet oxygen and superoxide free radicals' species. Furthermore, compounds 3b and 3c affinities towards calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were investigated using UV-Vis and fluorescence spectroscopic analysis. They revealed good binding characteristics towards CT-DNA with Kb values of 6.68 × 104 M-1 and 1.19 × 104 M-1 for 3b and 3c, respectively. In addition, compounds 3b and 3c ability to release free radicals on radiation were targeted to be used as cytotoxic compounds in vitro for colon (HCT116) and breast cancer (MDA-MB-231) cells. A significant reduction in the cell viability on illumination at 365 nm was observed, with IC50 values of 23 and 25 µM against HCT116 cells, and 30 and 9 µM against MDA-MB-231 cells for compounds 3b and 3c, respectively. In conclusion, compounds 3b and 3c exhibited remarkable DNA cleavage and cytotoxic activity on illumination at 365 nm which might be associated with free radicals' production in addition to having a good affinity for interacting with CT-DNA and BSA.

Pluripotent stem cell-derived CTLs targeting FGFR3-TACC3 fusion gene in osteosarcoma.

Osteosarcoma, a highly aggressive bone cancer, poses significant treatment challenges. This study investigates a novel approach utilizing induced pluripotent stem cells (iPSCs) engineered with the FGFR3-TACC3 fusion gene to generate cytotoxic T lymphocytes (CTLs) targeting osteosarcoma. The aim was to assess the efficacy of iPSC-derived CTLs in combating osteosarcoma progression. Abnormal expression of the FGFR3-TACC3 fusion gene was confirmed in osteosarcoma samples. iPSCs were successfully modified to express the fusion gene and were then differentiated into CTLs. In vitro experiments demonstrated that these modified CTLs effectively killed osteosarcoma cells, induced apoptosis, and inhibited migration and invasion. Findings were validated in in vivo experiments. This study suggests that iPSC-derived CTLs targeting FGFR3-TACC3 hold promise for personalized immunotherapy against osteosarcoma.