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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]

Ferroptosis is a way of cell death mainly due to the imbalance between the production and degradation of lipid reactive oxygen species, which is closely associated with various diseases. Endogenous hypochlorous acid (HOCl) mainly produced in mitochondria is regarded as an important signal molecule of ferroptosis. Therefore, monitoring the fluctuation of endogenous HOCl is beneficial to better understand and treat ferroptosis-related diseases. Inspired by the promising aggregation-induced emission (AIE) properties of tetraphenylethene (TPE), herein, we rationally constructed a novel AIE-based fluorescent probe, namely QTrPEP, for HOCl with nice mitochondria-targeting ability and high sensitivity and selectivity. Probe QTrPEP consisted of phenylborate ester and the AIE fluorophore of quinoline-conjugated triphenylethylene (QTrPE). HOCl can brighten the strong fluorescence through a specific HOCl-triggered cleavage of the phenylborate ester bond and release of QTrPE, which has been demonstrated by MS, HPLC, and DLS experiments. In addition, combining QTrPE-doped test strips with a smartphone-based measurement demonstrated the excellent performance of the probe to sense HOCl. The obtained favorable optical properties and negligible cytotoxicity allowed the use of this probe for tracking of HOCl in three different cells. In particular, this work represents the first AIE-based mitochondria-targeting fluorescent probe for monitoring the fluctuation of HOCl in ferroptosis. [ABSTRACT FROM AUTHOR]

Hypoxia (low-oxygen) is one of the most common characteristics of solid tumours. Exploiting tumour hypoxia to reductively activate Pt(IV) prodrugs has the potential to deliver toxic Pt(II) selectively and thus overcome the systemic toxicity issues of traditional Pt(II) therapies. However, our current understanding of the behaviour of Pt(IV) prodrugs in hypoxia is limited. Here, we evaluated and compared the aryl carbamate fluorogenic Pt(IV) complexes, CisNap and CarboNap, as well as the previously reported OxaliNap, as potential hypoxia-activated Pt(IV) (HAPt) prodrugs. Low intracellular oxygen concentrations (<0.1%) induced the greatest changes in the respective fluorescence emission channels. However, no correlation between reduction under hypoxic conditions and toxicity was observed, except in the case for CarboNap, which displayed significant hypoxia-dependent toxicity. Other aryl carbamate Pt(IV) derivatives (including non-fluorescent analogues) mirrored these observations, where carboplatin(IV) derivative CarboPhen displayed a hypoxia-selective cytotoxicity similar to that of CarboNap. These findings underscore the need to perform extensive structure activity relationship studies on the cytotoxicity of Pt(IV) complexes under normoxic and hypoxic conditions. [ABSTRACT FROM AUTHOR]

This study describes the rational development and synthesis of a benzothiazole-salicylaldehyde Schiff base probe 1. This probe is designed to function as a ratiometric fluorescent probe specifically for detecting ClO− ions, utilizing the imine bond as the fluorophore unit. Upon interaction with ClO− ions, probe 1 exhibits a redshift in its absorption spectrum from 435 nm to 450 nm. Moreover, in its emission spectrum, there is a ratiometric emission enhancement observed at 610 nm, providing a clear indication of the presence of ClO− ions. The sensitivity of probe 1 for detecting ClO− ions is quantified, revealing a lowest detection limit of 5.5 μM, indicating its potential for sensitive detection even at low concentrations of ClO− ions. Additionally, it has been successfully utilized for biological imaging purposes, demonstrating low cytotoxicity, which is crucial for its applicability in biological systems. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) with excellent biocompatibility is an ideal biomaterial for tissue repair. However, naturally derived ECM is inefficient in preventing wound infections caused by bacterial invasion. Therefore, developing ECM materials with antibacterial activity is crucial for tissue regeneration. In this work, ZnO–TA nanoparticles (NPs) were synthesized by using tannic acid (TA) and zinc chloride, with an average size of 26.3 nm as investigated by transmission electron microscopy (TEM). Compared to pure ZnO NPs, ZnO–TA NPs have improved dispersibility and lower cytotoxicity. Then, ECM composites were prepared by modifying acellular fish swim bladders (AFSBs) with different concentrations of ZnO–TA NPs and pure ZnO NPs, respectively. Results show that the ZnO–TA NPs are distributed more uniformly in the AFSBs with a longer release behavior. According to the in vitro antibacterial and biocompatibility experiments, ZnO–TA NP-modified AFSBs can maintain sufficient antibacterial activity against Escherichia coli and Staphylococcus epidermidis after 14 and 21 days, respectively, demonstrating a longer-lasting antibacterial activity along with a lower biotoxicity compared with pure ZnO NP-modified AFSBs. These findings suggest that the introduction of biosynthesized ZnO NPs is a promising strategy to improve the antibacterial activity of AFSBs for biomedical applications. [ABSTRACT FROM AUTHOR]

In the present study, pyroligneous acid, also known as wood vinegar, has been employed as reducing and stabilizing agent in the synthesis of silver nanoparticles (AgNPs) anchored on nanocellulose (NC). The idea is to confer the latter bactericidal properties for its typical uses such as in cosmetics and food-packing. It has been demonstrated that AgNPs can be directly produced onto NC in one-pot fashion while dramatically enhancing the kinetics of AgNPs synthesis (2 h for reaction completion) in comparison to the NC-less counterpart (10 days for reaction completion). Furthermore, NC allowed for a narrower size distribution of AgNPs. NC-supported and non-supported AgNPs had sizes of 5.1 ± 1.6 nm and 16.7 ± 4.62 nm, respectively. Immortalized human keratinocytes (HaCat) cells were then employed as model to evaluate the cytotoxicity of the AgNPs-NC compound. The latter was found not to impact cell proliferation at any formulation, while decreasing the viability by only 6.8% after 72 h. This study contributes to the development of more environmentally benign routes to produce nanomaterials and to the understanding of their impact on cells. [ABSTRACT FROM AUTHOR]

Chemotherapy is one of the most common therapeutic approaches in most cancers like prostate cancer, which has always faced limitations. The purpose of the present study was to design and prepare the targeted polymeric nanoparticles for the co-delivery of Paclitaxel (PTX) and Chrysin (CHR) to prostate cancer cells to improve the PTX therapeutic efficacy. Through the current research, the surface modification of the PTX/CHR-loaded PCL-PEG-PCL nanoparticles with chitosan and hyaluronic acid (PTX/CHR-PCEC-CS/HA) was successfully performed through the physical adsorption process. SEM results showed that this polymeric NPs had a homogeneous spherical structure. The encapsulation efficiency was 78.6 and 93.28% for CHR and PTX, respectively. It is important to mention that the controlled drug-release behavior of the PTX/CHR-PCEC-CS/HA was also investigated. The results demonstrated that the dual drug-loaded PCEC-CS/HA NPs had a significant effect on reducing the survival of the cancer. Also, the results exhibited that the cytotoxicity of the dual drug-loaded polymeric NPs in the PC3 cell line is significantly higher than in the HUVEC cell line. Based on the findings, the targeted PTX/CHR-PCEC-CS/HA NPs could be employed as a suitable candidate for the effective treatment of the prostate cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] Although photothermal therapy (PTT) is effective at killing tumor cells, it can inadvertently damage healthy tissues surrounding the tumor. Nevertheless, lowering the treatment temperature will reduce the therapeutic effectiveness. In this study, we employed 2,2′-((2Z,2′Z)-((4,4,9,9-Tetrahexyl-4,9-dihydro-s-indaceno[1,2- b :5,6- b ']dithiophene-2,7-diyl)bis(methanylylidene))bis(3-oxo-2,3-dihydro-1H-indene-2,1-diylidene)) dimalononitrile (IDIC), a molecule possessing a conventional acceptor–donor-acceptor (A-D-A) structure, as a photothermal agent (PTA) to facilitate effective mild photothermal therapy (mPTT). IDIC promotes intramolecular charge transfer under laser irradiation, making it a promising candidate for mPTT. To enhance the therapeutic potential of IDIC, we incorporated quercetin (Qu) into IDIC to form IDIC-Qu nanoparticles (NPs), which can inhibit heat shock protein (HSP) activity during the process of mPTT. Moreover, IDIC-Qu NPs exhibited exceptional water dispersibility and passive targeting abilities towards tumor tissues, attributed to its enhanced permeation and retention (EPR) effect. These advantageous properties position IDIC-Qu NPs as a promising candidate for targeted tumor treatment. Importantly, the IDIC-Qu NPs demonstrated controllable photothermal effects, leading to outstanding in vitro cytotoxicity against cancer cells and effective in vivo tumor ablation through mPTT. IDIC-Qu NPs nano-system enriches the family of organic PTAs and holds significant promise for future clinical applications of mPTT. [ABSTRACT FROM AUTHOR]

Corn is the second most cultivated crop in Brazil, the number-one country in pesticide consumption. Chemical control of weeds is performed using herbicides such as S-metolachlor with pre- and post-emergence action and thus the toxicity of herbicides constitutes a matter of great concern. The present investigation aimed to examine the effects of an S-metolachlor-based herbicide on Lactuca sativa L. (lettuce) and Zea mays L. (maize) utilizing various bioassays. The test solutions were prepared from commercial products containing the active ingredient. Seeds from the plant models were exposed in petri dishes and maintained under biochemical oxygen demand (BOD) at 24°C. Distilled water was negative and aluminium positive control. Macroscopic analyses (germination and growth) were conducted for both plant species, and microscopic analysis (cell cycle and chromosomal alterations) were performed for L. sativa root tip cells. Detrimental interference of S-metolachlor-based herbicide was noted with lettuce for all parameters tested reducing plant germination by over 50% and the germination speed by over 45% and showing a significant decrease in mitotic index, from 16.25% to 9,28% even on the lowest concentration tested. In maize, there was no significant interference in plant germination; however, speed of germination was significantly hampered, reaching a 51.22% reduction for the highest concentration tested. Data demonstrated that the herbicide was toxic as evidenced by its phyto- and cytotoxicity in L. sativa L. and Z. mays L. [ABSTRACT FROM AUTHOR]

Diabetic wound treatment continues to be a significant clinical issue due to higher levels of oxidative stress, susceptibility to bacterial infections, and chronic inflammatory responses during healing. We rationally developed and synthesized an ultra-small carbon dots (C-dots) loaded with zinc single-atom nanozyme (Zn/C-dots) with the aim of promoting wounds healing by nanocatalytic treatment, especially targeting its complex pathological microenvironment. Zinc single atoms and C-dots form a dual catalytic system with higher enzymatic activity. Furthermore, the Zn/C-dots nanozyme effectively enters cells, accumulates at mitochondria, and removes excess ROS, protecting cells from oxidative stress damage and limiting the release of pro-inflammatory cytokines, hence reducing inflammation. Zinc can synergistically increase the antibacterial action of C-dots (the effective antibacterial rate of 100 µg/mL Zn/C-dots was above 90 %). Unlike traditional C-dots, Zn/C-dots can cause endothelial cell migration and the formation of new blood vessels. In vitro cytotoxicity, blood compatibility, and in vivo toxicity studies of Zn/C-dots show that they are biocompatible. We subsequently utilized the Zn/C-dots nanozymes to treat diabetic rats' chronic wounds for external use, combining them with ROS-responsive hydrogels to create an antioxidative system (H-Zn/C-dots). The hydrogels anchored the Zn/C-dots nanozymes to the wound, allowing for long-term treatment. The results revealed that H-Zn/C-dots can considerably reduce inflammation, accelerate angiogenesis, collagen deposition, and promote tissue remodeling at the diabetic wound site. After 14 days, the wound area had decreased to approximately 9.19 %, making it a potential treatment. An ultra-small carbon dot with a zinc single-atom nanozyme was designed and manufactured. Zn/C-dots possess antibacterial, ROS-scavenging, and angiogenesis activities. In vivo , the multifunctional ROS-responsive hydrogel incorporating Zn/C-dots could speed up diabetic wound healing. [Display omitted] [ABSTRACT FROM AUTHOR]

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Summary Since the approval of the CD20‐targeting monoclonal antibody (mAb) rituximab for the treatment of lymphoma in 1997, mAb therapy has significantly transformed cancer treatment. With over 90 FDA‐approved mAbs for the treatment of various hematological and solid cancers, modern cancer treatment relies heavily on these therapies. The overwhelming success of mAbs as cancer therapeutics is attributed to their broad applicability, high safety profile, and precise targeting of cancer‐associated surface antigens. Furthermore, mAbs can induce various anti‐tumor cytotoxic effector mechanisms including antibody‐dependent cellular cytotoxicity (ADCC), antibody‐dependent cellular phagocytosis (ADCP), and complement‐dependent cytotoxicity (CDC), all of which are mediated via their fragment crystallizable (Fc) domain. Over the past decades, these effector mechanisms have been substantially improved through Fc domain engineering. In this review, we will outline the different approaches to enhance Fc effector functions via Fc engineering of mAbs, with a specific emphasis on the so‐called “HexaBody” technology, which is designed to enhance the hexamerization of mAbs on the target cell surface, thereby inducing greater complement activation, CDC, and receptor clustering. The review will summarize the development, preclinical, and clinical testing of several HexaBodies designed for the treatment of B‐cell malignancies, as well as the potential use of the HexaBody technology beyond Fc‐mediated effector functions. [ABSTRACT FROM AUTHOR]

Magnesium-enriched hydroxyapatite was synthesized and integrated with chitosan, forming a bio-compatible biocomposite (CH/Mg·HAP) to be applied as a carrier of oxaliplatin (OXN) with enhanced loading, release, and therapeutic activities. The developed CH/Mg·HAP displayed better loading (234.8 mg g−1) behavior as compared to the single phase of Mg·HAP (148.9 mg g−1). Based on steric analysis and advanced equilibrium modeling, the integration of chitosan enhanced the existence of loading sites up to 88.3 mg g−1 as compared to the existing loading receptors throughout Mg·HAP (69.4 mg g−1). This validates the impact of the integrated chemical groups and enhanced surface area. Additionally, the hybridizing reactions considerably affected the loading capacity of each receptor (n = 2.66 for CH/Mg·HAP and 2.15 for Mg·HAP). This also determined the orientation of the loaded OXN ions in a vertically oriented configuration that involves various types of multi-molecular processes. The energetic parameters, including loading energy (<40 KJ mol−1), suggested the dominant mechanistic impact of the physical processes (hydrogen binding and van der Waals forces). The composite also displays conterminous and regulated release patterns that extend for about 160 h at pH 5.5 and 200 h at pH 7.4. The kinetic modeling of the release activities, in addition to the obtained diffusion exponent (>0.45), indicated that erosion and diffusion reactions interact to control the releasing pathways. The unloaded CH/Mg·HAP exhibits considerable cytotoxicity against HCT-116 cancerous cells (17.8% cell viability) and its OXN-loaded sample exhibits significantly enhanced cytotoxicity (0.87% cell viability). [ABSTRACT FROM AUTHOR]

The synthesis and characterization of metal complexes have garnered significant attention due to their versatile applications in scientific and biomedical fields. In this research, two novel copper (Cu) complexes, [Cu(L)(L′)(H2O)2] (1) and [Cu(L)(Im)H2O] (2), where L = pyridine-2,6-dicarboxylic acid, L′ = 2,4-diamino-6-hydroxypyrimidine, and Im = imidazole, were investigated concerning their sonochemical synthesis, spectroscopic analysis, and biological activity. The complexes' structural characterization was achieved using analytical techniques, including single-crystal X-ray structure determination, FTIR, PXRD, TGA and DTA, SEM, TEM, and EDS. Complex (1) displayed a six-coordinated Cu2+ ion, while complex (2) exhibited a five-coordinated Cu2+ ion. The crystal structures revealed monoclinic (C2/c) and triclinic (P-1) space groups, respectively. Both complexes showcased zero-dimensional (0D) supramolecular networks, primarily driven by hydrogen bonding and π–π stacking interactions, which played pivotal roles in stabilizing the structures and shaping the unique supramolecular architecture. Both complexes demonstrated significant antioxidant activity, suggesting their capability to neutralize free radicals and mitigate oxidative stress-related diseases. Hemolysis percentages were less than 2%, per the ASTM F756-00 standard, indicating non-hemolytic behavior. Low cytotoxicity was observed against fibroblast and MCF-7 cell lines. They do not exhibit antibacterial activity against Escherichia coli and Staphylococcus aureus. These findings suggest that the synthesized Cu2+‒complexes hold considerable promise for applications in drug delivery and cancer treatment. This research contributes to the advancement of supramolecular chemistry and the development of multifunctional materials for diverse scientific and medical applications. [ABSTRACT FROM AUTHOR]

AbstractGeraniol, an acyclic monoterpene alcohol, has significant potential applications in various fields, including: food, cosmetics, biofuels, and pharmaceuticals. However, the current sources of geraniol mainly include plant tissue extraction or chemical synthesis, which are unsustainable and suffer severely from high energy consumption and severe environmental problems. The process of microbial production of geraniol has recently undergone vigorous development. Particularly, the sustainable construction of recombinant Escherichia coli (13.2 g/L) and Saccharomyces cerevisiae (5.5 g/L) laid a solid foundation for the microbial production of geraniol. In this review, recent advances in the development of geraniol-producing strains, including: metabolic pathway construction, key enzyme improvement, genetic modification strategies, and cytotoxicity alleviation, are critically summarized. Furthermore, the key challenges in scaling up geraniol production and future perspectives for the development of robust geraniol-producing strains are suggested. This review provides theoretical guidance for the industrial production of geraniol using microbial cell factories. [ABSTRACT FROM AUTHOR]

Antibacterial resistance requires an advanced strategy to increase the efficacy of current therapeutics in addition to the synthesis of new generations of antibiotics. In this study, copper oxide nanoparticles (CuO-NPs) were green synthesized using Moringa oleifera root extract. CuO-NPs fabricated into a form of aspartic acid-ciprofloxacin-polyethylene glycol coated copper oxide-nanotherapeutics (CIP-PEG-CuO) to improve the antibacterial activity of NPs and the efficacy of the drug with controlled cytotoxicity. These NPs were charachterized by Fourier transform infrared spectroscopy (FTIR), x-rays diffraction spectroscopy (XRD), scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). Antibacterial screening and bacterial chemotaxis investigations demonstrated that CIP-PEG-CuO NPs show enhanced antibacterial potential against Gram-positive and Gram-negative clinically isolated pathogenic bacterial strains as compared to CuO-NPs. In ex-vivo cytotoxicity CIP-PEG-CuO-nano-formulates revealed 88% viability of Baby Hamster Kidney 21 cell lines and 90% RBCs remained intact with nano-formulations during hemolysis assay. An in-vivo studies on animal models show that Staphylococcus aureus were eradicated by this newly developed formulate from the infected skin and showed wound-healing properties. By using specially designed nanoparticles that are engineered to precisely transport antimicrobial agents, these efficient nano-drug delivery systems can target localized infections, ensure targeted delivery, enhance efficacy through increased drug penetration through physical barriers, and reduce systemic side effects for more effective treatment. [ABSTRACT FROM AUTHOR]

COVID-19 remains a severe condition for many including immunocompromised individuals. There remains a need for effective measures against this and other respiratory infections, which transmit via virus-laden droplets that reach the nasal or oral mucosae. Nasal sprays offer potential protection against viruses. Such formulations should preserve normal nasal mucociliary function. The antiviral barrier efficacy and effects on mucociliary function of astodrimer sodium nasal spray (AS-NS) were evaluated and compared with other available nasal sprays—low pH hydroxypropyl methylcellulose (HPMC-NS), iota-carrageenan (Carr-NS), nitric oxide (NO-NS), and povidone iodine (PI-NS). Assays simulated clinical conditions. Antiviral barrier function and cell viability were assessed in airway cell monolayers, while a model of fully differentiated human nasal epithelium (MucilAir™) was utilized to evaluate tissue integrity, cytotoxicity, cilia beating frequency, and mucociliary clearance. AS-NS reduced infectious virus in cell monolayers and demonstrated a benign cytotoxicity profile. In human nasal epithelium ex vivo, AS-NS had no impact on mucociliary function (cilia beating nor mucociliary clearance). Carr-NS, HPMC-NS, NO-NS and PI-NS demonstrated limited antiviral effects, while HPMC-NS caused inhibition of mucociliary function. Astodrimer sodium nasal spray demonstrates an acceptable nonclinical efficacy and safety profile as a barrier nasal spray against respiratory viral infection in the nasal cavity. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles have wide range biological, biomedical and environmental applications. However, traditional nanofabrication of ZnONPs uses various toxic chemicals and organic solvents which limit their bio-applications. To overcome this hurdle, Bauhinia variegata derived buds extract was utilized to fabricate ZnONPs. The greenly generated ZnONPs were successfully prepared and extensively characterized using different analytical tools and the average crystalline size was calculated as 25.47 nm. Further, bioengineered ZnONPs were explored for multiple biological activities that revealed excellent therapeutic potentials. The antibacterial potential was determined using different bacterial strains. Pseudomonas aeruginosa (MIC: 137.5 µg/mL) was reported to be the most resistant variant while Bacillus subtilis (MIC: 34.38 µg/mL) was observed to be most susceptible bacterial strain. DPPH radical scavenging potential was measured to determine the antioxidant capacity of ZnONPs and the highest scavenging potential was observed as 82% at highest of 300 µg/mL. The fungicidal effect of green ZnONPs in comparison with Amphotericin B was assessed against five selected pathogenic fungal strains. The results revealed, Fusarium solani (MIC: 46.875 µg/mL) was least resistant and Aspergillus flavus (MIC: 187.5 µg/mL) was most resistant in fungicidal examination. Cytotoxicity potential of B.V@ZnONPs was analyzed against newly hatched nauplii of brine shrimps. The results for greenly produced ZnONPs was recorded as 39.78 µg/mL while 3.006 µg/mL was reported for positive control vincristine sulphate. The results confirmed the category of general cytotoxic for greenly synthesized nano sized B.V@ZnONPs. [ABSTRACT FROM AUTHOR]

Glioblastoma is one of the most aggressive and treatment‐resistant forms of primary brain cancer, posing significant challenges in effective therapy. This study aimed to enhance the effectiveness of glioblastoma therapy by developing a unique nanomedicine composed of Pluronic F127‐complexed PEGylated poly(glutamic acid)‐cisplatin (PLG‐PEG/PF127‐CDDP). PLG‐PEG/PF127‐CDDP demonstrated an optimal size of 133.97 ± 12.60 nm, facilitating efficient cell uptake by GL261 glioma cells. In vitro studies showed significant cytotoxicity against glioma cells with a half‐maximal (50%) inhibitory concentration (IC50) of 12.61 µg mL−1 at 48 h and a 72.53% ± 1.89% reduction in cell invasion. Furthermore, PLG‐PEG/PF127‐CDDP prolonged the circulation half‐life of cisplatin to 9.75 h in vivo, leading to a more than 50% reduction in tumor size on day 16 post‐treatment initiation in a murine model of glioma. The treatment significantly elevated lactate levels in GL261 cells, indicating enhanced metabolic disruption. Therefore, PLG‐PEG/PF127‐CDDP offers a promising approach for glioblastoma therapy due to its effects on improving drug delivery efficiency, therapeutic outcomes, and safety while minimizing systemic side effects. This work underscores the potential of polymer‐based nanomedicines in overcoming the challenges of treating brain tumors, paving the way for future clinical applications. [ABSTRACT FROM AUTHOR]

Background: Traditional medicine claims that Anodendron parviflorum has benefits for treating various human diseases. The present study seeks to understand better the phytochemical and LC–MS/MS-QTOF profiling of A. parviflorum's ethanolic extract and to investigate the properties of the different solvents of A. parviflorum for anti-inflammatory, antioxidant, antimicrobial, toxicity, and cytotoxic effects. Results: The quantitative methods exhibited higher total phenolics (327.16 ± 2.4 mg GAE/g dw), total flavonoid (109.82 ± 1.9 mg QE/g dw), and total alkaloid (14.13 ± 0.09%) content in ethanol extract. In contrast, a higher total extraction value (22.8 ± 0.6%) and total terpenoid (57.23 ± 0.06 mg LL/g dw) content was shown in the methanol extract of A. parviflorum. LC–MS/MS-QTOF analysis of its ethanolic extract revealed a notable occurrence of phenols and flavonoids. The ethanolic extract of A. parviflorum exhibited significant antioxidant activities with lower IC50 values in DPPH, phosphomolybdenum, and metal chelating and reducing power assay. The methanolic extract of A. parviflorum had the more significant anti-inflammatory property (94.55 ± 0.1%) in the bovine serum albumin assay. The extracts also demonstrated a higher inhibition zone against pathogenic bacteria. The ethanolic extract of A. parviflorum demonstrated substantial cytotoxicity against A549 cells. Conclusion: Consequently, these findings validate the use of A. parviflorum in traditional medical practices due to its bioactive compounds, which may have potential therapeutic value in various biomedical applications. Highlights: A. parviflorum leaves extract showed the presence of significant levels of alkaloids, flavonoids, phenols, and terpenoids. LC–MS/MS-QTOF analysis revealed notable bioactive compounds of A. parviflorum. The different extracts showed remarkable antioxidant and antimicrobial activities. The extracts exhibited less hemolytic and higher thrombolytic activities. It demonstrated significant cytotoxicity against A549 cell lines. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Five unreported and oxygenated ent‐rosane diterpenoids (ent‐RDs), Euphomillanols A—E (1—5), were isolated from Euphorbia milii. Among them, compounds 1 and 2 are unprecedented 7/7/6‐fused tricyclic 5,10‐seco‐ent‐RDs and possess a unique 11‐oxabicyclo[4.4.1]undeca‐1(10),5‐diene moiety, while 3 is characterized by a 1‐methyl‐6‐oxabicyclo[3.2.1]oct‐2‐ene motif of ring A. Their structures with absolute configurations were unambiguously determined by the extensive spectroscopic methods, X‐ray crystallography, and ECD calculation. Putative biosynthetic pathways for compounds 1—3 are proposed. All compounds exhibited antiadipogenic effects in 3T3‐L1 adipocytes, and the most potent compound 4 showed an EC50 value of 3.92 μmol/L with low cytotoxicity (IC50 > 89.54 μmol/L). [ABSTRACT FROM AUTHOR]

The repair and regeneration of cartilage is a challenge for scientists and clinical surgery. Achieving cell adhesion and regeneration, anti‐inflammatory, lubrication, targeted drug delivery and controlled release simultaneously in cartilage treatment are the goals of researchers. Polymer composites and hybrids have the potential to realize above functions in cartilage tissue engineering. This review refers to cartilage injuries, current clinical techniques, and their benefits and limitations, focusing on the most relevant and state of art of advanced polymers for cartilage tissue engineering. The frontier applications of multifunctional polymer composites and hybrids in cartilage tissue engineering are discussed in depth, including polymer scaffold, polymer bio‐lubricant, and zwitterionic polymer for drug delivery and sustained drug release. A summary of comprehensive properties of polymers such as processability, mechanical properties, biocompatibility, biodegradability, hydrophilicity, cytotoxicity, etc., and their mechanisms are analyzed. Furthermore, some key challenges and outstanding concerns on polymer‐based materials for cartilage tissue engineering are presented followed by future perspectives. Highlights: The state of art of advanced polymers for cartilage tissue engineering.The advanced bionic property and mechanism of polymer composites and hybrids.Polymers for scaffold, biolubricant, drug delivery, sustained drug release.Future perspectives on polymer composites, hybrids‐based cartilage materials. [ABSTRACT FROM AUTHOR]

Combining phytochemicals and nanotechnology to improve the unfavorable innate properties of phytochemicals and develop them into potent nanomedicines to enhance antitumor efficacy has become a novel strategy for cancer chemoprevention. Melanoma is the most aggressive, metastatic, and deadly disease of the primary cutaneous neoplasms. In this study, we fabricated phytoconstituent-derived zingerone nanoparticles (NPs) and validated their effects on cell adhesion and motility in melanoma B16F10 cells. Our data indicated that zingerone NPs significantly induced cytotoxicity and anti-colony formation and inhibited cell migration and invasion. Moreover, zingerone NPs dramatically interfered with the cytoskeletal reorganization and markedly delayed the period of cell adhesion. Our results also revealed that zingerone NPs-mediated downregulation of MMPs (matrix metalloproteinases) activity is associated with inhibiting cell adhesion and motility. We further evaluated the effects of zingerone NPs on Src/FAK /Paxillin signaling, our data showed that zingerone NPs significantly inhibited the protein activities of Src, FAK, and Paxillin, indicating that they play important roles in zingerone NP-mediated anti-motility and anti-invasion in melanoma cells. Accordingly, the phytoconstituent-zingerone NPs can strengthen the inhibition of tumor growth, invasion, and metastasis in malignant melanoma. Altogether, these multi-pharmacological benefits of zingerone NPs will effectively achieve the purpose of melanoma prevention and invasion inhibition. [Display omitted] • Nanosizing ginger phytoconstituent zingerone possesses superior anti-tumorigenesis. • Zingerone NPs promoted cytotoxicity and anti-cell adhesion in melanoma cells. • Zingerone NPs-mediated downregulation of cell invasion and MMPs activity. • Src/FAK/Paxillin signaling is involved in zingerone NP-mediated anti-cell motility. [ABSTRACT FROM AUTHOR]

Populus × tomentiglandulosa (PT), a tree endemic to Korea, shows promising potential as a natural therapeutic agent owing to its potent anti-inflammatory properties. However, the isolation and analysis of phytochemical compounds in PT and related species remains underexplored. Therefore, this study aims to investigate the biochemical profile of PT and evaluate its extracts and fractions for anti-inflammatory activities. Nine compounds were isolated, including two novel flavonoids (luteolin 7-O-ß-D-glucuronide butyl ester and chrysoeriol 7-O-ß-Dglucuronide butyl ester) from the Salicaceae family for the first time. The ethyl acetate fraction exhibited significant radical scavenging activity against various radicals, including DPPH, ABTS+, •OH, and O2 - radicals. PT extracts and the ethyl acetate fraction showed minimal cytotoxicity in Raw 264.7 macrophages at concentrations below 500 and 100 µg/mL, respectively. Furthermore, PT extracts and fractions significantly suppressed the protein expression of proinflammatory mediators (iNOS and IL-6) in LPS-stimulated Raw 264.7 macrophages, highlighting their potent anti-inflammatory effects. These findings suggest that PT holds promise as a valuable natural therapeutic intervention for various oxidative stress and inflammation-related disorders, underscoring the need for further exploration of its clinical applications. [ABSTRACT FROM AUTHOR]

Extranodal natural killer/T cell lymphoma (ENKTL) shows a high rate of recurrence after chemoradiotherapy. Drug resistance can be mediated by the cargo of small extracellular vesicles (sEVs). Here, we show that high abundance of the transmembrane glycoprotein CD98hc in tumor cells and serum sEVs was associated with ENKTL progression and drug resistance. Mechanistically, PEGylated-asparaginase (PEG-asp) treatment, a common therapy against ENKTL, promoted the translocation of the transcription factor ATF4 to the nucleus, where it was stabilized by USP1 and subsequently increased CD98hc expression. CD98hc delivered in tumor cell–derived sEVs increased tumor cell proliferation and drug resistance in a cultured human NK lymphoma cell line, animal models, and samples from patients with refractory/relapse ENKTL. Moreover, inhibiting both USP1 and EV secretion synergistically enhanced the cytotoxicity of PEG-asp. These data suggest that targeting CD98hc in the treatment of ENKTL may be beneficial in overcoming drug resistance. Editor's summary: Extranodal natural killer/T cell lymphoma (ENKTL) is treated with PEGylated asparaginase (PEG-asp), but drug resistance is common. Liao et al. found that limiting the trafficking of a glycoprotein could overcome drug resistance. Ubiquitin carboxyl-terminal hydrolase 1 (USP1) stabilized the transcription factor ATF4, which promoted CD98hc expression. Knocking out CD98hc in tumor cells and small extracellular vesicles (sEVs) sensitized cells to PEG-asp treatment, whereas CD98hc-enriched sEVs suppressed the effects of PEG-asp in mice, suggesting that targeting CD98hc may be explored in the treatment of ENKTL. —Amy E. Baek [ABSTRACT FROM AUTHOR]

Pasteurella multocida toxin (PMT) is one of the most important virulence factors of Pasteurella multocida type D. Pasteurella multocida infection has caused enormous economic losses in the pig farming industry. Although it is well known that this bacterial infection causes progressive atrophic rhinitis, its effects on other organ tissues in pigs are unclear. In this study, PMT was expressed and purified, and the cytotoxic effects of PMT on four types of swine cells, LLC-PK1, PAM, IPEC, and ST, were investigated. LLC-PK1 exhibited the highest sensitivity to the cytotoxic effects of PMT. Our studies revealed that a PMT concentration of 0.1 µg/kg can lead to weight loss, whereas a PMT concentration of 0.5 µg/kg can lead to death in mice. PMT causes damage to the intestines, kidneys, lungs, livers, and spleens of mice. Furthermore, PMT caused acute death in pigs at treatment concentrations greater than 5 µg/kg; at PMT concentration of 2.5 µg/kg, weight loss occurred until death. PMT mainly caused damage to the hearts, lungs, livers, spleens and kidneys of pigs. The organ coefficient showed that damage to the heart and kidneys was the most severe and caused the renal pelvis and renal pyramid to dissolve and become cavitated. Pathology revealed hemorrhage in the lungs, liver, and spleen, and the kidneys were swollen and vacuolated, which was consistent with the damaged target organs in the mice. In conclusion, these findings demonstrate that PMT is extremely toxic in vitro and in vivo, causing damage to various organs of the body, especially the kidneys and lungs. This study provides a theoretical basis for the in-depth exploration of the cytotoxic effects of PMT on target organs. [ABSTRACT FROM AUTHOR]

AbstractPeptaibols are fungal peptides that exhibit efficacy against pathogen microorganisms. Trichokonin VI (TK-VI) and trichokonin VIII (TK-VIII) are known peptaibols isolated from the endolichenic fungi Hypocrea sp. Previous investigations reported that trichokonin VI presents antiproliferative effects on tumor cells. This study is pioneering in elucidating the genotoxic effects of TK-VI and TK-VIII, contributing to the thorough assessment of their safety as potential therapeutic agents. The present investigation aimed to evaluate the genotoxicity of TK-VI and TK-VIII on CHO-K1 cells. Cytotoxicity was evaluated using the XTT assay and clonogenic survival assays, followed by evaluation of DNA damage using the comet assay and micronucleus test conducted in vitro. The XTT assay results indicated IC50 values of 10.30 µM and 9.89 µM for TK-VI and TK-VIII, respectively. The clonogenic survival assay indicated that concentrations of 10 µM or higher completely inhibited the cell colony formation. In the comet assay, both TK-VI and TK-VIII increased the DNA damage score and the frequency of comet nuclei in all tested concentrations. In the micronucleus assay, TK-VI and TK-VIII at 10 µM increased the frequency of MN in CHO-K1 cells. Both TK-VI and TK-VIII exhibited genotoxic effects. Our findings underscore the importance of considering the genotoxicological safety of peptaibols, particularly when assessing their potential for other biological activities. [ABSTRACT FROM AUTHOR]

Chemodynamic therapy represents a novel tumor therapeutic modality via triggering catalytic reactions in tumors to yield highly toxic reactive oxygen species (ROS). Nevertheless, low efficiency catalytic ability, potential systemic toxicity and inefficient tumor targeting, have hindered the efficacy of chemodynamic therapy. Herein, a rationally designed catalytic nanoplatform, composed of folate acid conjugated liposomes loaded with copper peroxide (CP) and chloroquine (CQ; a clinical drug) (denoted as CC@LPF), could power maximal tumor cytotoxicity, mechanistically via maneuvering endogenous and exogenous copper for a highly efficient catalytic reaction. Despite a massive autophagosome accumulation elicited by CP-powered autophagic initiation and CQ-induced autolysosomal blockage, the robust ROS, but not aberrant autophagy, underlies the synergistic tumor inhibition. Otherwise, this combined mode also elicits an early onset, above all, long-term high-level existence of immunogenic cell death markers, associated with ROS and aberrant autophagy -triggered endoplasmic reticulum stress. Besides, CC@LPF, with tumor targeting capability and selective tumor cytotoxicity, could elicit intratumor dendritic cells (mainly attributed to CQ) and tumor infiltrating CD8+ T cells, upon combining with PD-L1 therapeutic antibody, further induce significant anti-tumor effect. Collectively, the rationally designed nanoplatform, CC@LPF, could enhance tumor chemoimmunotherapy via deploying endogenous plus exogenous copper and remodeling tumor microenvironment. [ABSTRACT FROM AUTHOR]

Lemna aequinoctialis (duckweed) is the smallest and fast-growing aquatic plant species producing protein-rich biomass with high protein nutritional value, phytoremediation capacity, and nutrient removal from wastewater. Duckweed may also be used as a new potential bioreactor for biological products, such as vaccines, antibodies, and pharmaceutical proteins. Based upon the potential importanc of L. aequinoctialis in phytoremediation and as a bioreactor the aim of this study was to (1) characterize the chemical and nutritional profiles of L. aequinoctialis biomass utilizing an integrated multi-trophic aquaculture system (IMTA) and a pond, and (2) investigate the cytotoxic potential of different concentrations of organic extracts and fractions using the MTT bioassay. EDXRF and ICP-MS analyses indicated the presence of trace elements in lower amounts in relation to the biomass of L. aequinoctialis in the lagoon, emphasizing the importance of plant inclusion management to reduce bioaccumulation of these elements. Analysis of mineral profiles, fatty acids, and amino acids indicated a satisfactory nutritional composition for the use of biomass as a bioproduct. Pigment analysis showed a high concentration of carotenoids, especially astaxanthin. After standardizing the controls, the MTT cell viability test was carried out utilizing rat hepatoma cell line (HTC), which are metabolizing cells that were treated with aqueous or ethanolic extracts and the dichloromethane, ethyl acetate, and methanol fractions at different concentrations. No apparent cytotoxic potential was observed following treatments, since there was no significant reduction in cell viability. Therefore, this study provides information regarding the biomass of L. aequinoctialis derived from the IMTA system, which might support further research into the application of this species as a bioproduct. [ABSTRACT FROM AUTHOR]

Among the most important aquaculture resources for our country, salmon and trout stand out. Their production has increased significantly in recent decades, making them two of the most valuable resources in economic terms. However, high aquaculture production has allowed many pathogens to proliferate, causing infectious diseases and significant production losses. Piscirickettsia salmonis is a gram‐negative, facultative intracellular bacterium that is responsible for causing severe disease in a variety of salmonid fish species. Despite the significant impact of P. salmonis on aquaculture, effective treatments for this disease remain limited. Current prevention and control strategies often include antibiotics and vaccines. However, these treatments have shown varying degrees of efficacy. A promising approach involves synthesizing bioactive analog compounds with antibacterial properties. Quinones, secondary metabolites that are abundant in nature, have become a focal point of interest due to their diverse physiological activities, including antibiotic, insecticidal, antifungal, and anticancer properties. In this study, it is shown the synthesis of series 6‐bromo‐7‐arylaminoisoquinoline‐5,8‐quinones, the characterization of these compounds using classical spectroscopic methods such as one‐dimensional nuclear magnetic resonance (NMR), FT‐IR (infrared), mass spectrometry, and the biological activity against Piscirickettsia salmonis. The brominated derivative compounds showed no cytotoxicity at any concentration evaluated. Furthermore, the infectivity of P. salmonis after treatment with the analog compounds indicated that derivatives methyl 6‐bromo‐7‐((4‐methoxyphenyl)amino)‐1,3‐dimethy‐5,8‐dioxo‐5,8‐dihydroisoquinoline‐4‐carboxylate (4b) and methyl 7‐((4′‐amino‐[1,1′‐biphenyl]‐4‐yl)amino)‐6‐bromo‐1,3‐dimethy‐5,8‐dioxo‐5,8‐dihydroisoquinoline‐4‐carboxylate (4g) reduced the bacterial load at 25 μg/mL concentration. [ABSTRACT FROM AUTHOR]

ABSTRACT Nano‐sized bivalent metal complexes, specifically [M(L)2] with L = 2‐((E)‐((4,5‐dimethyl‐2‐(((E)‐4‐methylbenzylidene)amino)phenyl)‐imino)methyl)benzenethiol] (C23H22N2S) and M = Cu (II) (C1), Co (II) (C2), Ni (II) (C3), and Zn (II) (C4), underwent synthesis and subsequent characterization. Elemental analyses, infrared, NMR, mass, electronic, magnetic susceptibility, conductivity assessments, and X‐ray diffraction studies were used to assess our bivalent metal complexes. DFT studies were used to study the tautomeric equilibrium of the tridentate thio‐Schiff base ligand (HL), via the DFT\B3LYP method in connection with a 6–311G* correlation consistent basis set. Two tautomers, which are thione and thiol forms, were studied to estimate the predominant one. The metal formed four coordinated with the tridentate N2S donor thio‐Schiff base to form octahedral geometry complexes. The SEM, TEM, XRD, AFM, and EDX of the studied complexes unveiled distinct and strong diffraction peaks, signifying their crystalline nature and providing evidence of their particle sizes being within the nano‐size. The crystal sizes calculated for all complexes were determined to be ranging from 27.73 to 76.39 nm. The interactions between metal complexes and calf thymus DNA, and their potential for mimicking insulin activity, were investigated in a controlled lab setting by measuring their ability to inhibit alpha‐amylase. The antimicrobial potential of thio‐Schiff base ligand (HL) plus complexes (C1–C4) were tested. The viscosity and UV–Vis absorption determinations were utilized to assess the calf thymus DNA (CT‐DNA) interaction with the nano‐sized metal (II) chelates. Our flow cytometry data indicate significant levels of apoptosis and cell cycle arresting in both liver and breast cancer cell lines. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Phytocannabinoids inhibit the aggregation and neurotoxicity of the neurotoxic Alzheimer's disease protein β amyloid (Aβ). We characterised the capacity of five proprietary medical cannabis extracts, heated and non‐heated, with varying ratios of cannabidiol and Δ9‐tetrahydrocannabinol and their parent carboxylated compounds to protect against lipid peroxidation and Aβ‐evoked neurotoxicity in PC12 cells.Neuroprotection against lipid peroxidation and Aβ1–42‐induced cytotoxicity was assessed using the thiazolyl blue tetrazolium bromide (MTT) assay. Transmission electron microscopy was used to visualise phytocannabinoid effects on Aβ1–42 aggregation and fluorescence microscopy.Tetrahydrocannabinol (THC)/tetrahydrocannabinolic acid (THCA)‐predominant cannabis extracts demonstrated the most significant overall neuroprotection against Aβ1–42‐induced loss of PC12 cell viability. These protective effects were still significant after heating of extracts, while none of the extracts provided significant neuroprotection to lipid peroxidation via tbhp exposure. Modest inhibition of Aβ1–42 aggregation was demonstrated only with the non‐heated BC‐401 cannabis extract, but overall, there was no clear correlation between effects on fibrils and conferral of neuroprotection.These findings highlight the variable neuroprotective activity of cannabis extracts containing major phytocannabinoids THC/THCA and cannabidiol (CBD)/cannabidiolic acid (CBDA) on Aβ‐evoked neurotoxicity and inhibition of amyloid β aggregation. This may inform the future use of medicinal cannabis formulations in the treatment of Alzheimer's disease and dementia. [ABSTRACT FROM AUTHOR]

Recent advances in whole genome sequencing have revealed an immense microbial potential for the production of therapeutic small molecules, even from well‐known producers. To access this potential, we subjected prominent antimicrobial producers to alternative antiproliferative assays using persistent cancer cell lines. Described herein is our discovery of hirocidins, novel secondary metabolites from Streptomyces hiroshimensis with antiproliferative activities against colon and persistent breast cancer cells. Hirocidin A is an unusual nine‐membered carbocyclic maleimide and hirocidins B and C are relatives with an unprecedented, bridged azamacrocyclic backbone. Mode of action studies show that hirocidins trigger mitochondrion‐dependent apoptosis by inducing expression of the key apoptotic effector caspase‐9. The discovery of new cytotoxins contributes to scaffold diversification in anticancer drug discovery and the reported modes of action and concise total synthetic route for variant A set the stage for unraveling specific targets and biochemical interactions of the hirocidins. [ABSTRACT FROM AUTHOR]

Significant advances have been made in materials for biomedical applications, including tissue engineering, bioimaging, cancer treatment, etc. In the past few decades, nanostructure-mediated therapeutic strategies have been developed to improve drug delivery, targeted therapy, and diagnosis, maximizing therapeutic effectiveness while reducing systemic toxicity and side effects by exploiting the complicated interactions between the materials and the cell and tissue microenvironments. This review briefly introduces the differences between the cells and tissues of tumour or normal cells. We summarize recent advances in tumour microenvironment-mediated therapeutic strategies using nanostructured materials. We then comprehensively discuss strategies for fabricating nanostructures with cancer cell-specific cytotoxicity by precisely controlling their composition, particle size, shape, structure, surface functionalization, and external energy stimulation. Finally, we present perspectives on the challenges and future opportunities of nanotechnology-based toxicity strategies in tumour therapy. [ABSTRACT FROM AUTHOR]

Background: GALNTs (UDP-GalNAc; polypeptide N-acetylgalactosaminyltransferases) initiate mucin-type O-GalNAc glycosylation by adding N-GalNAc to protein serine/threonine residues. Abnormalities in O-GalNAc glycosylation are involved in various disorders such as Parkinson's disease (PD), a neurodegenerative disorder. GALNT9 is potentially downregulated in PD patients. Methods: To determine whether GALNT9 enrichment ameliorates cytotoxicity related to PD-like variations, a pcDNA3.1-GALNT9 plasmid was constructed and transfected into SH-SY5Y cells to establish a GALNT9-overexpressing cell model. Results: Downregulation of GALNT9 and O-GalNAc glycosylation was confirmed in our animal and cellular models of PD-like variations. GALNT9 supplementation greatly attenuated cytotoxicity induced by MPP+ (1-Methyl-4-phenylpyridinium iodide) since it led to increased levels of tyrosine hydroxylase and dopamine, reduced rates of apoptosis, and significantly ameliorated MPP+-induced mitochondrial dysfunction by alleviating abnormal levels of mitochondrial membrane potential and reactive oxygen species. A long-lasting mPTP (mitochondrial permeability transition pores) opening and calcium efflux resulted in significantly lower activity in the cytochrome C-associated apoptotic pathway and mitophagy process, signifying that GALNT9 supplementation maintained neuronal cell health under MPP+ exposure. Additionally, it was found that glycans linked to proteins influenced the formation of protein aggregates containing α-synuclein, and GALNT9 supplement dramatically reduced such insoluble protein aggregations under MPP+ treatment. Glial GALNT9 predominantly appears under pathological conditions like PD-like variations. Conclusions: GALNT9 enrichment improved cell survival, and glial GALNT9 potentially represents a pathogenic index for PD patients. This study provides insights into the development of therapeutic strategies for the treatment of PD. [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]

Fluorophlogopite is a well-known fluorosilicate glass-ceramic derivative known for its bioactivity, machinability and optimal mechanical properties. There is limited information regarding its antibacterial and biocompatible properties. This research paper presents the synthesis and characterization of a novel Boron-doped Fluorphlogopite [KMg 3 (Al 0.5 B 0.5)Si 3 O 10 F 2 ] aiming to improve its antibacterial properties intended for anticariogenic applications. The combustion synthesis method was employed, with oxalyl dihydrazide (ODH) (C 2 H 6 N 4 O 2) serving as the fuel. X-ray Diffraction (XRD) analyses unveiled a monoclinic crystal system, showcasing a P2 1 space group, and an average crystallite size of approximately 28 nm. Morphological scrutiny divulged clustered, irregularly shaped, cluster-like structures. The energy gap was determined to be around 4.97 ± 0.0062 eV. Fourier-Transform Infrared (FTIR) spectroscopy depicted the presence of characteristic bonds. BET analysis indicated the presence of a large surface area and porous structure (mesopores), which may contribute to lower MIC and MBC values, enhancing antibacterial effectiveness. The antibacterial activity, evaluated via agar well diffusion, yielded an 8 mm zone of inhibition. Furthermore, the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) against S mutans were determined to be 2 mg/ml and 16 mg/ml, respectively. The biocompatibility of the synthesized KMg 3 (Al 0.5 B 0.5)Si 3 O 10 F 2 was assessed through the MTT assay, indicating non-toxic behavior at a concentration of 12 μg/ml with 98 % cell viability, while showing moderate toxicity with 61 % viable cells at its highest concentration of 200 μg/ml. [ABSTRACT FROM AUTHOR]

An in‐depth investigation was conducted on a promising composite material (BiVO4/TiO2), focusing on its potential toxicity, photoinduced catalytic properties, as well as its antibiofilm and antimicrobial functionalities. The preparation process involved the synthesis of 2D TiO2 using the lyophilization method, which was subsequently functionalized with sphere‐like BiVO4 through wet impregnation. Finally, we developed BiVO4/TiO2 S‐scheme heterojunctions which can greatly promote the separation of electron‐hole pairs to achieve high photocatalytic performance. The evaluation of concentration‐ and time‐dependent viability inhibition was performed on human lung carcinoma epithelial A549 cells. This assessment included the estimation of glutathione levels and mitochondrial dehydrogenase activity. Significantly, the BiVO4/TiO2 composite demonstrated minimal toxicity towards A549 cells. Impressively, the BiVO4/TiO2 composite exhibited notable photocatalytic performance in the degradation of rhodamine B (k=0.135 min−1) and phenol (k=0.016 min−1). In terms of photoinduced antimicrobial performance, the composite effectively inactivated both gram‐negative E. coli and gram‐positive E. faecalis bacteria upon 60 minutes of UV‐A light exposure, resulting in a significant log 6 (log 10 CFU/mL) reduction in bacterial count. In addition, a 49 % reduction of E. faecalis biofilm was observed. These promising results can be attributed to the unique 2D morphology of TiO2 modified by sphere‐like BiVO4, leading to an increased generation of (intracellular) hydroxyl radicals, which plays a crucial role in the treatments of both organic pollutants and bacteria. This research has significant potential for various applications, particularly in addressing environmental contamination and microbial infections. [ABSTRACT FROM AUTHOR]

Prior research has indicated that bisphosphonates (BPs) can improve periodontal disease because of their anti-osteoporosis properties. In vitro studies have shown that BPs induce cytotoxicity, inhibit wound healing, and thus affect periodontal disease. Denosumab and BPs have alternative indications. BP and denosumab are not known to correlate with gingival disorders. We assessed such a relationship by applying Bayesian and nonproportional analyses to data in the US FDA Adverse Event Reporting System (FAERS) database. The study analyzed BPs and denosumab-reported incidents with preferred terms found in the narrow Standardized MedDRA Queries for gingival disorders. A total of 5863 reported cases of gingival disorders were associated with five BPs (alendronate, pamidronate, ibandronate, risedronate, and zoledronate) and denosumab. More than 15% of patients with gingival disorders related to BPs and denosumab other than denosumab were hospitalized over short- or long-term periods. Our findings indicated BPs and denosumab had significant reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) with respect to gingival disorders. Pamidronate had the highest association (ROR = 64.58, PRR = 57.99, IC = 5.71), while the weakest association was found with denosumab (ROR = 3.61, PRR = 3.60, IC = 1.77). Significant associations were found between the six drugs and gingival pain, gingival recession, gingivitis, periodontal disease, and periodontitis. In conclusion, our comprehensive overview of the correlations, clinical characteristics, and prognoses of BPs and denosumab-related gingival disorders suggests that these issues deserve continued surveillance and appropriate management. [ABSTRACT FROM AUTHOR]

In this paper, we describe the synthesis of indolyl aryl sulfonamide conjugates (6 a–n). The anti‐tumour activity was assessed on three human cancer cell lines: A‐549 (lung), HeLa (cervix), and MCF‐7 (breast). Nocodazole was used as a standard drug by employing the MTT assay method. The results show that the compounds 6 b, 6 l, and 6 m have shown more potent activity as compared to the standard drug Nocodazole. In a cell survivability test (MCF‐10 A), three potent compounds (6 b, 6 l, and 6 m) were evaluated against the normal breast cell line, although neither of them displayed any significant cytotoxicity with IC50 values greater than 78.45 μM. Furthermore, the compounds 6 b, 6 l, and 6 m were tested for tyrosine kinase EGFR inhibitory action using Combretastatin A‐4 as the reference drug. The in vitro tubulin polymerization inhibitory activity indicates that the compounds 6b and 6 l showed promising potency with IC50 values of 2.40±0.02 and 2.34±0.03 mM, respectively. In addition to this, molecular docking studies of compounds 6 b, 6 l, and 6 m demonstrated that these compounds had more EGFR binding interactions. The potent compounds 6 b, 6 l, and 6 m were subjected to in silico pharmacokinetic assessment by SWISS, ADME, and pkCSM. While the compounds 6 b, 6 l, and 6 m followed five filters (Lipinski rule, Ghose rule, Veber rule, Egan rule, and Muegge rule) without any deviation. [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]

High molecular weight polyethylenimine (HMW PEI; branched 25 kDa PEI) has been widely investigated for gene delivery due to its high transfection efficiency. However, the toxicity and lack of targeting to specific cells have limited its clinical application. In the present investigation, L-3, 4‐dihydroxyphenylalanine (L-DOPA) was conjugated on HMW PEI in order to target L-type amino acid transporter 1 (LAT-1) and modulate positive charge density on the surface of polymer/plasmid complexes (polyplexes). The results of biophysical characterization revealed that the PEI conjugates are able to form nanoparticles ≤ 180 nm with the zeta potential ranging from + 9.5–12.4 mV. These polyplexes could condense plasmid DNA and protect it against nuclease digestion at the carrier to plasmid ratios higher than 4. L-DOPA conjugated PEI derivatives were complexed with a plasmid encoding human interleukin-12 (hIL-12). Targeted polyplexes showed up to 2.5 fold higher transfection efficiency in 4T1 murine mammary cancer cell line, which expresses LAT-1, than 25 kDa PEI polyplexes prepared in the same manner. The cytotoxicity of these polyplexes was also substantially lower than the unmodified parent HMW PEI. These results support the use of L-3, 4‐dihydroxyphenylalanine derivatives of PEI in any attempt to develop a LAT-1 targeted gene carrier. [ABSTRACT FROM AUTHOR]

A recent scientific investigation has shown promising results of selenium nanoparticles (SeNPs) for the anticancer and antimicrobial activities. This study aims to evaluate the effects of PVP SeNPs on bacterial strains, including Staphylococcus aureus (S. aureus), Bacillus cereus (B. cereus), Klebsiella pneumoniae (K. pneumoniae), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa). Also, its antitumor activity against the MRC-5 carcinoma cell line. SeNPs were prepared via gamma irradiation using PVP as a capping agent, and their size and morphological structure were determined using HRTEM. The size of the SeNPs ranged from 36 to 66.59 nm. UV–vis spectra confirmed the formation of SeNPs, while FTIR measurement confirmed a change in the PVP structure after adding selenium nanoparticles. The highest effect was reported on HepG2 by an IC50 with a value of 8.87 µg/ml, followed by HeLa, PC3, MCF-7, and Caco2 cell lines, respectively. Furthermore, ZOI reached 36.33 ± 3.05 mm. The best value of the minimum inhibitory concentration (MIC) was 0.313 µg/ml. Scanning electron microscope (SEM) imaging against bacteria showed deformations and distortions in their structures. Transmission electron (TEM) revealed ultrastructure changes in treated bacteria because of the free radicals that made cytotoxicity which confirmed by Electron spin resonance (ESR). [ABSTRACT FROM AUTHOR]

Background: Toxoplasmosis, caused by Toxoplasma gondii , poses serious health issues for humans and animals. Individuals with impaired immune systems are more susceptible to severe toxoplasmosis. Pregnant women infected by T. gondii can face the possibility of birth defects and miscarriages. While pyrimethamine and sulfadiazine are commonly used drugs in clinical practice, concerns over their side effects and resistance are on the rise. A spider peptide XYP1 isolated from Lycosa coelestis had potent anti-T. gondii effects, but it had a high synthesis cost and strong cytotoxicity. Methods: This study intended to modify XYP1 for producing derived peptides via amino acid truncation and substitution. The anti-T. gondii effect was evaluated by trypan blue staining assay and killing experiment of RH strain tachyzoites. The CCK8 and hemolysis assays were used to compare their safeties. The morphological changes of T. gondii were observed by scanning electron microscope and transmission electron microscope. In addition, the mechanism of XYP1 against T. gondii through RNA-sequencing was further explored. Results: In vivo and in vitro experiments revealed that XYP1-18 and XYP1-18-1 had excellent anti-T. gondii activity with lower cytotoxicity and hemolysis activity than XYP1. XYP1, XYP1-18, and XYP1-18-1 were able to disrupt the surface membrane integrity of T. gondii tachyzoites, forming pores and causing the disruption of organelles. Furthermore, RNA-sequencing analysis indicated that XYP1 could stimulate the host immune response to effectively eliminate T. gondii and lessen the host's inflammatory reaction. Conclusions: XYP1-18 had lower cytotoxicity and hemolysis activity than XYP1, as well as significantly extending the survival time of the mice. XYP1 played a role in host inflammation and immune responses, revealing its potential mechanism. Our research provided valuable insights into the development and application of peptide-based drugs, offering novel strategies and directions for treating toxoplasmosis. [ABSTRACT FROM AUTHOR]

Cancer continues to pose a significant global health challenge, with gastrointestinal (GI) cancers among the most prevalent and deadly forms. These cancers often lead to high mortality rates and demand the use of potent cytotoxic chemotherapeutics. For example, 5-fluorouracil (5-FU) forms the backbone of chemotherapy regimens for various GI cancers, including colorectal cancer. While these chemotherapeutics efficiently kill cancer cells, they frequently cause off-target effects such as chemotherapy-induced mucositis (CIM), characterized by debilitating symptoms like pain, nausea, and diarrhoea, necessitating medical intervention. In this study, we elucidated the potential of melatonin and misoprostol to reduce 5-FU-induced small intestinal mucositis. Morphological and cellular changes in the jejunum, along with colonic faecal water content were quantified in rats as markers for CIM. Additionally, the effects of melatonin were investigated in vitro on 5-FU treated murine intestinal organoids. The results showed that melatonin prevented villus atrophy in the rat jejunal mucosa and upheld cell viability in murine intestinal organoids. In contrast, misoprostol alone or in combination with melatonin did not significantly affect CIM caused by 5-FU. These in vivo and in vitro experiments provided promising insights that melatonin may be used as a preventive and/or adjuvant combination therapy to prevent and reduce CIM, holding the potential to enhance cancer treatment outcomes and improve patient quality-of-life. [ABSTRACT FROM AUTHOR]

The strasseriolide macrolides show promising in vitro and in vivo activities against P. falciparum and T. cruzi, the parasites causing malaria and Chagas disease, respectively. However, the as yet poor understanding of structure/activity relationships and the fact that one family member proved systemically toxic for unknown reasons render a more detailed assessment of these potential lead compounds difficult. To help overcome these issues, a collective total synthesis was devised. The key steps consisted of a ring closing alkyne metathesis (RCAM) reaction to forge a common macrocyclic intermediate followed by a hydroxy‐directed ruthenium catalyzed trans‐hydrostannation of the propargyl alcohol site thus formed. The resulting alkenyltin derivative served as the central node of the synthesis blueprint, which could be elaborated into the natural products themselves as well as into a set of non‐natural analogues according to the concept of diverted total synthesis. The recorded biological data confirmed the potency of the compounds and showed the lack of any noticeable cytotoxicity. The "northern" allylic alcohol subunit was recognized as an integral part of the pharmacophore, yet it provides opportunities for chemical modification. [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]

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]

AbstractThe vibrations were attributed to 5-chloro-2-mercaptobenzimidazole using FTIR and FT-Raman spectroscopy. The optimized geometrical parameters, IR intensity, and the Raman activity of the vibrational bands were estimated using the Becke three-parameter Lee-Yang-Parr functional and the 6-311++G(d,p) level of theory. These findings are compared with the experimental data. The molecule’s HOMO-LUMO energy gap is found to be 4.418 eV. UV-Vis analysis reveals that the π→π* transition, which happens when electron density shifts from nitrogen, sulfur, and chlorine atoms in the molecule, to the electrons of the C-C bonds of the ring. Total density of states was used to assess the molecular orbital contributions. There are 47α and 47β electrons totaling 94 electrons in the DOS spectrum. NBO investigations indicate that a considerable stabilizing energy of 30.37 and 30.90 Kcal/mol was revealed by the lone pair transition of N1 and N3 atoms to π*(C7-C8) and π*(C4-C9). The more electrophilic region, as seen by the red zone in MEP mapping, lies in the vicinity of the nitrogen and sulfur atoms. The molecule’s hydrogen atoms are found in the blue nucleophilic area. The theoretical chemical shifts for 1H and 13C NMR ranged from 7.03 to 8.23 ppm and 113.10 to 207.31 ppm, respectively. The docking research showed that the molecule attached to protein 1AQU with a greater binding energy of −6.8 Kcalmol−1. The cytotoxicity of the sample was evaluated against a MCF-7 cell line (IC50 = 16.54 µg/ml) and exhibited a good breast cancer action. In addition, ADMET prediction has been used to estimate the medicinal applicability of the chemical. [ABSTRACT FROM AUTHOR]