Use Of Agents Research Articles

Comprehensive Overview of Methods of Pregnancy Termination in Macaques and Marmosets

Limited information is available concerning the termination of pregnancy in non-human primates. Thus, a comprehensive review of this topic will be beneficial for veterinary staff in laboratories, zoos, and wildlife rehabilitation centers. The most relevant studies concerning the termination of viable and non-viable pregnancy in non-human primates were analyzed, and dosages, administration routes, adverse effects, and the efficacy of the drugs used are reported. The literature revealed that termination of pregnancy is most commonly performed in marmosets and macaques. The combination of mifepristone and misoprostol was reported to be effective and fast-acting in terminating first-trimester pregnancy in macaques, while cloprostenol was identified as the best agent for use in marmosets. This review also provides insights about the limitations of previously described methods of pregnancy termination and discusses potential alternatives and areas for future investigation.

8-Anilino-1-naphthalenesulfonate-Conjugated Carbon-Coated Ferrite Nanodots for Fluoromagnetic Imaging, Smart Drug Delivery, and Biomolecular Sensing

Background: Superparamagnetic properties and excitation independence have been incorporated into carbon-decorated manganese ferrite nanodots (MnFe@C) to introduce an economical and safer multimodal agent for use in both T1-T2 MRI and fluorescence-based imaging to replace the conventional highly toxic heavy metal contrast agents. Methods: The surface conjugation of 8-anilino-1-naphthalenesulfonate (ANS) to MnFe@C nanodots (ANS-MnFe@C) enhances both longitudinal and transverse MRI relaxation, improves fluorescence for optical imaging, and increases protein detection sensitivity, showing higher multimodal efficacy in terms of molar relaxivity, radiant efficiencies, and fluorescence sensitivity compared to MnFe@C. Results: The band gap energy was determined using Tauc’s equation to be 3.32 eV, while a 72% quantum yield demonstrated that ANS-MnFe@C was highly fluorescent, with the linear range and association constant calculated using the Stern–Volmer relation. The synthesized ANS-MnFe@C demonstrated excellent selectivity and sensitivity for bovine serum albumin (BSA), with a nanomolar detection limit of 367.09 nM and a broad linear range from 0.015 to 0.225 mM. Conclusions: In conclusion, ANS-MnFe@C holds ease of fabrication, good biocompatibility, as assessed in A375 cells, and an effective pH-sensitive doxorubicin release profile to establish anticancer activity in lung cancer cell line (A549), highlighting its potential as an affordable therapeutic agent for multimodal imaging, drug delivery, and protein sensing.

Functional response and predatory potential of Neoseiulus newsami (Acari: Phytoseiidae) against Megalurothrips usitatus (Thysanoptera: Thripidae)

Megalurothrips usitatus, is an important pest of cowpeas Vigna unguiculata, that causes severe damage to cowpea crops in Southeast Asia and Hainan Province in China. Neoseiulus newsami is a natural enemy of M. usitatus that was first reported from Ledong Li Autonomous County, Hainan, China. Here, we evaluated the potential of N. newsami as a biocontrol agent for use against M. usitatus. In laboratory tests, N. newsami showed a similar rate of attack on this pest as did the better-known species Neoseiulus barkeri. The functional response curve of N. newsami fed M. usitatus showed that more 1st instar prey were consumed by N. newsami at higher prey densities, indicating a Type III functional. The maximum attack coefficient (a) was 0.063 ± 0.011 and the handling time per consumed prey (Th) was 0.58 ± 0.09. The maximum attack rate (T/Th) was 41.37. Neoseiulus newsami showed higher predation and oviposition rates than did N. barkeri or Neoseiulus cucumeris. Our results suggest that N. newsami has a higher predation capacity against M. usitatus.

Penetration of Intracoronal Bleaching Agents Across a Calcium Silicate-Based Coronal Barrier in Pulpless Immature Permanent Teeth: An In Vitro Study.

Tooth bleaching procedures on nonvital teeth have been performed for crown discoloration caused by regenerative endodontic therapy (RET). However, leakage of bleaching agents across the root canal can be detrimental. This study aimed to assess and compare the penetration levels of hydrogen peroxide (HP) from different bleaching agents across calcium silicate-based coronal barriers in immature permanent teeth. Fifty extracted single-rooted human teeth were randomly divided into four groups (n = 10): Group I (HH)-35% hydrogen peroxide (HP); Group II (SS)-a mixture of sodium perborate (SP) powder and saline; Group III (SH)-a mixture of SP powder and 30% HP liquid; Group IV (CP)-10% carbamide peroxide gel. The control group (Group V, CC) was treated with distilled water. The bleaching agent was replaced on the 4th day, and penetration analysis was performed on the 7th day using ferro thiocyanate (FTC) method and a UV-spectrophotometer at a wavelength of 480 nm. Compared with the control group, the SH group (SP mixed with HP) showed a significant difference, indicating substantial HP penetration across the root canal space (p value < 0.0001). Intergroup comparisons also revealed a significant difference between the SS and SH groups (p value < 0.0001), suggesting that the SS group had less penetration. Compared with other bleaching agents, SP mixed with saline/water resulted in the lowest HP penetration in the pulp canals of the RET-simulated tooth models. This study is the first to investigate HP penetration from different bleaching agents in teeth that have undergone RET, identifying the safest bleaching agent for use in these cases. This study also provides a foundation for further research to develop precise guidelines for nonvital tooth bleaching protocols in RET-treated teeth.

Immunomodulatory Activity and Inhibitory Effects of Viscum album on Cancer Cells, Its Safety Profiles and Recent Nanotechnology Development.

Viscum album has been employed traditionally to treat various ailments including as add-on therapy for cancer treatment. V.album formulations have been employed as adjuvants in cancer treatment due to their immunomodulatory activities as well as to alleviate the side effects of conventional cancer therapies. The present review provides updated information from the past 10 years on the immunomodulatory activity and inhibitory effects of V.album on cancer cells, its safety profile, and recent nanotechnology development. V.album extracts and their bioactive phytochemicals, particularly lectins, viscotoxins, and polyphenols, have demonstrated immunomodulatory activity and inhibitory effects against various types of cancer, with low cytotoxicity and side effects, in experimental studies and demonstrated promising anticancer activity in clinical studies in cancer patients. V.album extracts have been shown to enhance immune function by promoting cytokine secretion and inducing both innate and adaptive immune responses, which can help improve immune surveillance against cancer cells. The development of V.album nanoparticles has boosted their biological activities, including inhibitory activity on cancer cells, and could possibly reduce undesired side effects of the plant. Further prospective studies on the plant as a source of new medicinal agents for use as an adjuvant in the treatment of cancer must be performed to provide sufficient efficacy and safety data.

Anastatus japonicus Ashmead, a potential biological control agent of Riptortus pedestris (Fabricius)

Riptortus pedestris (Fabricius) (Hemiptera: Alydidae) is a significant pest of soybean production in China. While biological control would be a desirable means to manage this pest, little research on the use of parasitoids against R. pedestris has been done. In this study, for the parasitoid Anastatus japonicus Ashmead (Hymenoptera: Eupelmidae), we measured the parasitism rate in R. pedestris, the emergence rate of parasitoid progeny, and mortality of eggs from host-feeding. Parasitoids of different ages were assessed against R. pedestris eggs of various ages under laboratory conditions. In addition, the development and longevity of A. japonicus reared on R. pedestris egg were also measured. We found the maximum parasitism rate of A. japonicus was 54.6% on R. pedestris egg. And the maximum emergence rate of A. japonicus was 50.0% from all offered R. pedestris eggs. Mortality from parasitoid host-feeding was 43.8% when 1-day-old R. pedestris eggs were offered to 6-day-old A. japonicus parasitoids. For older eggs, parasitism rates were lower, making 1-day old eggs the optimal host age for use in mass rearing. Longevity of the offspring (F1) generation of A. japonicus were 10 (males) and 23 (females) days. The developmental times of the F1 offspring were 21.9 (males) and 21.7 (females) days. The parasitism rate and the rate of mortality due to host feeding caused by parasitoid progeny (F1) generation were 56.3, and 43.8%, respectively. Among all the eggs parasitized not subjected to host feeding, 98.5% yielded adult parasitoids. Among all emerging A. japonicus, the sex ratio (as % female) in the F2 generation was 45%, which was significantly higher than that in the first generation (F1) (18%). These results suggest that A. japonicus could be a potential biological control agent for use against R. pedestris.

Study of the amino acid composition of Chimáphila umbelláta herb

The therapeutic use of amino acids is a promising direction of modern pharmacy and medicine. Amino acids play an important role in the complex pharmacological action of herbal medicines, and also improve the assimilation of other biologically active substances (BAS) and are able to potentiate their pharmacological activity. A sufficiently rich source of amino acids are medicinal plants that combine in their composition a complex of groups of BAS, thanks to which they have a combined effect on the body The purpose of the work was the study the amino acids of Chimáphila umbelláta herb with the aim of expanding the knowledge about the chemical composition of the herbal raw material and the development of a phytotherapeutic agent with nephroprotective and anti-inflammatory properties in the future. The object of the study was Chimáphila umbelláta dried herb (supplier «World of Herbs», Kharkiv). The research was performed by gas chromatography-mass spectrometry using a SHIMADZU GC-MS-QP2010 chromatographic system connected to an electron ionization ion source and a single-quadrupole MS 5975C (Shimadzu Technologies). A robotic autosampler and a split/non-split injection port were used. The separation of amino acids was carried out in an Rxi-5 ms (capillary column of Restek Corporation – length 30 m, outer diameter 0.25 mm and thickness liquid–stationary phase 0.25 μm) with a liquid stationary phase of 5% diphenyl and 95% polysiloxane, with helium at purity 99.99% as a carrier gas at a constant flow of 1.47 ml/min. Standard mixtures of L-amino acids: alanine, serine, valine, threonine, leucine, isoleucine, proline, aspartic acid, glutamic acid, lysine, methionine, phenylalanine, and tyrosine (Sigma-Aldrich GmbH, Steinheim, Germany) were used for the analysis. Amino acids were identified by comparing the mass spectra of compounds with data from the NIST14 and WRT10 libraries, and a mixture of standard samples was used to identify and quantify amino acids. The content of 7 amino acids, of which 3 are essential amino acids (L-valine, isoleucine, L-leucine) were identified in Chimáphila umbelláta herb. The largest amount contains L-glutamic acid (14.469 µg/g), the smallest – L-leucine (0.050 µg/g). The obtained results are important in the development of a phytotherapeutic agent for use in diseases of the kidneys and urinary tract. The amino acids identified in the studied raw materials play an important role, so L-glutamic acid participates in protein and carbohydrate metabolism, stimulates oxidation processes, helps detoxify and remove ammonia from the body, increases the body’s resistance to hypoxia. Alanine has the ability to reduce the risk of developing kidney stones, it is the basis of normal metabolism in the body, helps fight hypoglycemia; helps to moderate fluctuations in blood glucose levels between meals. The content of aspartic acid is also important – the precursor of lysine and the donor of amino groups in the biosynthesis of substitute amino acids. The quantitative content of amino acids in Chimáphila umbelláta herb was studied by the method of gas chromatography-mass spectroscopy. According to the results of the study, the content of amino acids was determined in the following order: L-glutamic acid &gt; L-alanine &gt; L-aspartic acid &gt; L-valine &gt; L-proline &gt; isoleucine &gt; L-leucine. The results of the conducted research indicate a rather high and diverse content of amino acids in Chimáphila umbelláta herb, which can improve the balance of phytoremedies and dietary supplements for the purpose of prevention of deficiency of this class of biologically active substances.

Macrophages directly kill bladder cancer cells through TNF signaling as an early response to BCG therapy.

The Bacillus Calmette-Guérin (BCG) vaccine is the oldest cancer immunotherapeutic agent in use. Despite its effectiveness, its initial mechanisms of action remain largely unknown. Here, we elucidate the earliest cellular mechanisms involved in BCG-induced tumor clearance. We developed a fast preclinical in vivo assay to visualize in real time and at single-cell resolution the initial interactions among bladder cancer cells, BCG and innate immunity using the zebrafish xenograft model. We show that BCG induced the recruitment and polarization of macrophages towards a pro-inflammatory phenotype, accompanied by induction of the inflammatory cytokines tnfa, il1b and il6 in the tumor microenvironment. Macrophages directly induced apoptosis of human cancer cells through zebrafish TNF signaling. Macrophages were crucial for this response as their depletion completely abrogated the BCG-induced phenotype. Contrary to the general concept that macrophage anti-tumoral activities mostly rely on stimulating an effective adaptive response, we demonstrate that macrophages alone can induce tumor apoptosis and clearance. Thus, our results revealed an additional step to the BCG-induced tumor immunity model, while providing proof-of-concept experiments demonstrating the potential of this unique model to test innate immunomodulators.

Learning Multi-Agent Cooperation via Considering Actions of Teammates.

Recently value-based centralized training with decentralized execution (CTDE) multi-agent reinforcement learning (MARL) methods have achieved excellent performance in cooperative tasks. However, the most representative method among these methods, Q-network MIXing (QMIX), restricts the joint action Q values to be a monotonic mixing of each agent's utilities. Furthermore, current methods cannot generalize to unseen environments or different agent configurations, which is known as ad hoc team play situation. In this work, we propose a novel Q values decomposition that considers both the return of an agent acting on its own and cooperating with other observable agents to address the nonmonotonic problem. Based on the decomposition, we propose a greedy action searching method that can improve exploration and is not affected by changes in observable agents or changes in the order of agents' actions. In this way, our method can adapt to ad hoc team play situation. Furthermore, we utilize an auxiliary loss related to environmental cognition consistency and a modified prioritized experience replay (PER) buffer to assist training. Our extensive experimental results show that our method achieves significant performance improvements in both challenging monotonic and nonmonotonic domains, and can handle the ad hoc team play situation perfectly.

Development and Optimization of Nasal Composition of a Neuroprotective Agent for Use in Neonatology after Prenatal Hypoxia.

The intranasal route of drug administration is characterized by high bioavailability and is considered promising for rapid delivery of drugs with systemic action to the central nervous system (CNS), bypassing the blood-brain barrier. This is particularly important for the use of neuroprotective drugs in the treatment of brain tissue damage in infants caused by the effects of intrauterine hypoxia. The creation of new dosage forms for neonatology using mathematical technologies and special software in pharmaceutical development allows for the creation of cerebroprotective drugs with controlled pharmaco-technological properties, thus reducing time and resources for necessary research. We developed a new nasal gel formulation with Angiolin using a Box-Behnken experiment design for the therapy of prenatal CNS damage. It was found that the consistency characteristics of the nasal gel were significantly influenced by the gelling agent and mucoadhesive component-sodium salt of carboxymethylcellulose. We optimized the composition of nasal gel formulation with Angiolin using the formed models and relationships between the factors. The optimized nasal gel composition demonstrated satisfactory thixotropic properties. The 1% gel for neuroprotection with Angiolin, developed for intranasal administration, meets all safety requirements for this group of drug forms, showing low toxicity and no local irritant or allergic effects.

Implications of eucalyptol anaesthesia on juvenile tambaqui Colossoma macropomum: Examining behavioural, muscular, cardiac, and haematological responses

This study aimed to evaluate the anaesthetic efficacy and safety of eucalyptol (ECL) in promoting full body immobilisation (anaesthesia), muscle relaxation, and cardiac activity in juvenile tambaqui, C. macropomum. Fish with an average weight of 30.8 ± 4.3 g and a length of 11.9 ± 0.7 cm were used. Initially, specimens underwent anaesthetic baths at ECL concentrations of 300, 400, 500, 600, 700, and 800 μL.L−1 for behavioural assessment. Thereafter, concentrations of 600, 700, and 800 μL.L−1 were arbitrarily selected for further testing, including electrophysiological recordings (EMG and ECG) over 300 s. Additionally, blood samples were collected before and after anaesthesia at 700 μL.L−1 ECL to analyse haematological responses. A total of 10 juveniles were used in each test and recording, divided into three groups: a) control (baseline recording), b) fish exposed only to the vehicle (water mixed with ethanol), and c) fish subjected to ECL for induction and subsequent recovery. The results indicated that higher concentrations of ECL more effectively promoted full body immobilisation (full anaesthesia). The electromyogram revealed significant decreases in muscle contraction power during anaesthetic induction at the three tested concentrations, indicating pronounced muscle relaxation. The electrocardiogram demonstrated a significant reduction in heart rate in fish induced with 700 μL.L−1 (41 ± 4 BPM) and 800 μL.L−1 ECL (35 ± 5 BPM), and the traces from exposure to ECL (600, 700, and 800 μL.L−1 ECL) showed slight, albeit reversible, arrhythmia, which preceded a bradycardic state. All animals gradually returned to sinus rhythm within the appropriate time threshold, suggesting a safe condition for recovery at all concentrations. Haematological results showed that only glucose levels (146.625 ± 30.95 mg.dL−1) were significantly altered compared to the control (76 ± 19.94 mg.dL−1) and ethanol (97.5 ± 16.15 mg.dL−1) groups, with homeostasis resuming after manipulation. In conclusion, ECL was effective in promoting anaesthesia, leading to complete body immobilisation of C. macropomum at concentrations ranging from 300 to 800 μL.L−1 with appropriate induction and recovery times. Concentrations of 600 to 800 μL.L−1 induced pronounced muscle relaxation and cardiac depression without posing a life-threatening scenario. ECL can act safely and reversibly as an anaesthetic agent for use in non-invasive procedures in tambaqui and potentially in other teleost species.

Comparison of Antiviral Immune Responses in Healthy Cats Induced by Two Immune Therapeutics.

Effective immunotherapeutic agents for use in cats are needed to aid in the management of intractable viral diseases, including feline infectious peritonitis (FIP) infection. The objectives of this study were to compare two different immune stimulants for antiviral activity in cats: (1) TLR 2/6-activating compound polyprenyl immunostimulant; (PI) and (2) liposome Toll-like receptor 3/9 agonist complexes (LTCs) to determine relative abilities to stimulate the induction of type I (IFN-α, IFN-β) and type II (IFN-γ) interferon immune responses in vitro and to study the effects of treatment on immune responses in healthy cats. Cytokine and cellular immune responses to PI and LTC were evaluated using peripheral blood mononuclear cells (PBMCs) from healthy cats incubated with LTC and PI at indicated concentrations using reverse transcriptase polymerase chain reaction assays and ELISA assays. The effects of the immune stimulants on inhibiting FIPV replication were assessed using a feline macrophage cell line (fcwf-4). Cytokine and cellular immune responses to PI and LTC were evaluated in blood samples from healthy cats treated with PI and LTC, using reverse transcriptase polymerase chain reaction (RT-PCR) and ELISA assays. In the in vitro studies, both compounds triggered the upregulated expression of IFN-α, IFN-γ, and IL-1β genes in cat PBMC, whereas treatment with LTC induced significantly greater expression of IFN-α and IFN-γ on Day 1 and IL-1b on Day 3. There was significant protection from FIPV-induced cytopathic effects when fcwf-4 cells were treated with conditioned medium from LTC-activated leukocytes. In the healthy cat study (in vivo), both PI and LTC increased the mRNA signal for IFN-α, IFN-γ, and IL-1β above baseline at multiple time points with statistically greater increases in the LTC group on either Day 1 (IFN-α, IFN-γ) or Day 3 (IL-1β). In addition, RANTES increased over time in cats treated with the LTC. Both LTC and PI protocols induced immune-enhancing effects, suggesting a possible clinical use for the management of chronic infectious diseases like FIP. Activating the TLR 3 and 9 pathways (LTC) induced superior broad interferon production in vitro than the activation of the TLR 2 and 6 pathways (PI).

Immunomodulatory Effect of Cordyceps militaris Polysaccharide on RAW 264.7 Macrophages by Regulating MAPK Signaling Pathways.

Polysaccharide is one of the principal bioactive components found in medicinal mushrooms and has been proven to enhance host immunity. However, the possible mechanism of immunomodulatory activity of Cordyceps militaris polysaccharide is not fully understood. Hot water extraction and alcohol precipitation, DEAE-Sephadex A-25 chromatography, and Sephadex G-100 chromatography were used to isolate polysaccharide from C. militaris. A high-molecular-weight polysaccharide isolated from C. militaris was designated as HCMP, which had an Mw of 6.18 × 105 Da and was composed of arabinose, galactose, glucose, mannose, and xylose in a mole ratio of 2.00:8.01:72.54:15.98:1.02. The polysaccharide content of HCMP was 91.2% ± 0.16. The test in vitro showed that HCMP activated mouse macrophage RAW 264.7 cells by enhancing phagocytosis and NO production, and by regulating mRNA expressions of inflammation-related molecules in RAW 264.7 cells. Western blotting revealed that HCMP induced the phosphorylation of mitogen-activated protein kinases (MAPKs). Moreover, using inhibitors of MAPKs decreased the mRNA levels of inflammation-related molecules induced by HCMP. These data evidenced that the immunomodulatory effect of HCMP on RAW 264.7 macrophages was mediated via the MAPK signaling pathway. These findings suggested that HCMP could be developed as a potent immunomodulatory agent for use in functional foods and dietary supplements.

Physico-Chemical and Biological Features of Fluorine-Substituted Hydroxyapatite Suspensions.

Infections related to orthopedic/stomatology surgery are widely recognized as a significant health concern. Therefore, the development of new materials with superior biological properties and good stability could represent a valuable alternative to the classical treatments. In this paper, the fluorine-substituted hydroxyapatite (FHAp) suspension, with the chemical formula Ca10(PO4)6(OH)2-2xF2x (where x = 0.05), was prepared using a modified coprecipitation technique. Stability studies were conducted by zeta potential and ultrasound measurements for the first time. The X-ray diffraction (XRD) patterns of FHAp powders displayed a hexagonal structure akin to that of pure hydroxyapatite (HAp). The XPS general spectrum revealed peaks corresponding to the constituent elements of fluorine-substituted hydroxyapatite such as calcium, phosphorus, oxygen, and fluorine. The purity of the obtained FHAp samples was confirmed by energy-dispersive X-ray spectroscopy (EDS) studies. The FHAp morphology was evaluated by scanning electron microscopy (SEM) measurements. Fourier-transform infrared spectroscopy (FTIR) studies were performed in order to study the vibrational properties of the FHAp samples. The FHAp suspensions were tested for antibacterial activity against reference strains such as Staphylococcus aureus 25923 ATCC, Escherichia coli ATCC 25922, and Candida albicans ATCC 10231. Additionally, the biocompatibility of the FHAp suspensions was assessed using human fetal osteoblastic cells (hFOB 1.19 cell line). The results of our biological tests suggest that FHAp suspensions are promising candidates for the future development of new biocompatible and antimicrobial agents for use in the biomedical field.

Bioactivity and antibacterial effect of star anise biosynthesized silver nanoparticles against Streptococcus mutans: an in vitro study

BackgroundSilver nanoparticles (AgNPs) are receiving a lot of attention as a prospective antibacterial agent for use in caries prevention. The objective of this study was to investigate the bioactivity and antibacterial effect of silver nanoparticles biosynthesized using Star Anise against Streptococcus mutans (S.mutans).MethodsThe bioactive components of the Star Anise were assessed by employing the gas chromatography-mass spectrometry technique. The antibacterial activities of Star Anise Biosynthesized Silver Nanoparticles against S.mutans bacteria were evaluated using Bauer and Kirby’s disc diffusion mechanism and the minimum inhibitory concentration.ResultsSilver nanoparticles biosynthesized using Star Anise revealed high antioxidant activity. AgNPs inhibited S. mutans with a 16 mm inhibition zone diameter and demonstrated an 80 µg/ml minimum inhibitory concentration.ConclusionsBiologically synthesized AgNPs made from aqueous extract of Star anise appear to be a potential and effective bactericidal agent against S.mutans that can be used to prevent dental caries.

Arsenic Trioxide Suppresses Angiogenesis in Non-small Cell Lung Cancer via the Nrf2-IL-33 Signaling Pathway.

Non-Small Cell Lung Cancer (NSCLC) ranks as a leading cause of cancer-related mortality, necessitating the urgent search for cost-effective and efficient anti-NSCLC drugs. Our preliminary research has demonstrated that arsenic trioxide (ATO) significantly inhibits NSCLC angiogenesis, exerting anti-tumor effects. In conjunction with existing literature reports, the Nrf2-IL-33 pathway is emerging as a novel mechanism in NSCLC angiogenesis. This study aimed to elucidate whether ATO can inhibit NSCLC angiogenesis through the Nrf2-IL-33 pathway. Immunohistochemistry was employed to assess the expression of Nrf2, IL-33, and CD31 in tumor tissues from patients with NSCLC. DETA-NONOate was used as a nitric oxide (NO) donor to mimic high levels of NO in the tumor microenvironment. Western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay were utilized to evaluate the expression of Nrf2 and IL-33 in the NCI-H1299 cell line. Subcutaneous xenograft models were established in nude mice by implanting NCI-H1299 cells to assess the anti-tumor efficacy of ATO. High expression levels of Nrf2 and IL-33 were observed in tumor samples from patients with NSCLC, and Nrf2 expression positively correlated with microvascular density in NSCLC. In vitro, NO (released from 1mM DETA-NONOate) promoted activation of the Nrf2-IL-33 signaling pathway in NCI-H1299 cells, which was reversed by ATO. Additionally, both Nrf2 deficiency and ATO treatment significantly attenuated NOinduced IL-33 expression. In vivo, both ATO and the Nrf2 inhibitor ML385 demonstrated significant inhibitory effects on angiogenesis tumor growth. Nrf2-IL-33 signaling is usually activated in NSCLC and positively correlates with tumor angiogenesis. ATO effectively disrupts the activation of the Nrf2-IL-33 pathway in NSCLC and thus inhibits angiogenesis, suggesting its potential as an anti-angiogenic agent for use in the treatment of NSCLC.

Infrared Fluorescence-guided Surgery for Tumor and Metastatic Lymph Node Detection in Head and Neck Cancer.

In patients with head and neck cancer (HNC), surgical removal of cancerous tissue presents the best overall survival rate. However, failure to obtain negative margins during resection has remained a steady concern over the past 3 decades. The need for improved tumor removal and margin assessment presents an ongoing concern for the field. While near-infrared agents have long been used in imaging, investigation of these agents for use in HNC imaging has dramatically expanded in the past decade. Targeted tracers for use in primary and metastatic lymph node detection are of particular interest, with panitumumab-IRDye800 as a major candidate in current studies. This review aims to provide an overview of intraoperative near-infrared fluorescence-guided surgery techniques used in the clinical detection of malignant tissue and sentinel lymph nodes in HNC, highlighting current applications, limitations, and future directions for use of this technology within the field. Keywords: Molecular Imaging-Cancer, Fluorescence © RSNA, 2024.

Remimazolam for anesthesia and sedation in pediatric patients: a scoping review.

Anesthetic management of pediatric patients poses several challenges and the optimal anesthetic agent for use in this population is still a matter of debate. We systematically searched PubMed/MEDLINE and Google Scholar from their inception for studies that investigated the role and potential applications of remimazolam, a novel ultra-short-acting benzodiazepine, in pediatric patients. Furthermore, in March 2024, an update of the literature search along with an additional post-hoc search on the EMBASE database were performed. A total of fourteen pertinent studies which spanned the 2021-2023 period explored remimazolam as either the primary or adjuvant hypnotic agent for inducing and/or maintaining general anesthesia or sedation. Preliminary evidence derived from these studies highlighted that remimazolam is a safe and effective option for both sedation and general anesthesia in pediatric patients, particularly those with concurrent mitochondrial disorders, myopathic diseases, or at risk for malignant hyperthermia. Moreover, the current evidence suggested that remimazolam may contribute to reducing preoperative anxiety and postoperative delirium in children. Its favorable pharmacodynamic and pharmacokinetic profile demonstrated potential safety, effectiveness, and ease-of-use in various perioperative pediatric contexts, making it suitable for integration into specific protocols, such as intraoperative monitoring of evoked potentials and management of difficult intubation. Notwithstanding these promising findings, further research is essential to determine optimal dosages, establish conclusive evidence of its superiority over other benzodiazepines, and elucidate the impact of genetic factors on drug metabolism.

Proof of stability of an RSV Controlled Human Infection Model challenge agent

In 2018, SGS Belgium NV developed RSV-NICA (Respiratory Syncytial Virus-Nasobronchial Infective Challenge Agent), an RSV type A challenge agent for use in RSV Controlled Human Infection Model (CHIM) studies.It is widely recognized that the stability of RSV can be influenced by a variety of environmental parameters, such as temperature and pH. Consequently, our objective was to evaluate the stability of the viral titer of RSV-NICA following five years of controlled storage and to determine the uniformity of the viral titers across different vials of a GMP-qualified batch of RSV-NICA. In addition, we examined the capacity of RSV-NICA to infect human primary airway epithelial cells (MucilAir™), the principal target cells of RSV, and evaluated the influence of single and recurrent freeze–thaw cycles on the infectious viral titer of the challenge agent.The aliquoted RSV-NICA virus stock was subjected to standard virological and molecular methods to gather data on the titer and consistency of the viral titer contained within 24 representative vials of the stock. Our findings illustrate that over a span of five years of cryo-storage, the infectious viral titer in 75% of the tested vials exhibited a comparable average infectious viral titer (4.75 ± 0.06 vs 4.99 ± 0.11; p-value = 0.14). A considerable reduction down to an undetectable level of infectious virus was observed in the remaining vials. RSV-NICA demonstrated its capacity to effectively infect differentiated human airway epithelial cells, with active virus replication detected in these cells through increasing RSV genome copy number over time. Virus tropism for ciliated cells was suggested by the inhibition of cilia beating coupled with an increase in viral RNA titers. No discernable impact on membrane barrier function of the epithelial lung tissues nor cytotoxicity was detected. Pooling of vials with infectious titers > 4.0 log10 TCID50/ml and freeze-thawing of these combined vials showed no deterioration of the infectious titer. Furthermore, pooling and re-aliquoting of vials spanning the entire range of viral titers (including vials with undetectable infectious virus) along with subjecting the vials to three repeated freeze–thaw cycles did not result in a decrease of the infectious titers in the tested vials.Taken together, our findings indicate that long-term cryo-storage of vials containing RSV-NICA challenge agent may influence the infectious viral titer of the virus, leading to a decrease in the homogeneity of this titer throughout the challenge stock. However, our study also demonstrates that when heterogeneity of the infectious titer of an RSV stock is observed, rounds of pooling, re-aliquoting and subsequent re-titration serve as an effective method not only to restore the homogeneity of the infectious titer of an RSV-A stock, but also to optimize patient-safety, scientific and operational aspects of viral inoculation of study participants during at least the period of one RSV CHIM trial. RSV-NICA is a stable, suitable CHIM challenge agent that can be utilized in efficacy trials for RSV vaccines and antiviral entities.

In vitro assessment of the effect of magnetic fields on efficacy of biosynthesized selenium nanoparticles by Alborzia kermanshahica

Cyanobacteria represent a rich resource of a wide array of unique bioactive compounds that are proving to be potent sources of anticancer drugs. Selenium nanoparticles (SeNPs) have shown an increasing potential as major therapeutic platforms and led to the production of higher levels of ROS that can present desirable anticancer properties. Chitosan–SeNPs have also presented antitumor properties against hepatic cancer cell lines, especially the Cht-NP (Chitosan–NPs), promoting ROS generation and mitochondria dysfunction. It is proposed that magnetic fields can add new dimensions to nanoparticle applications. Hence, in this study, the biosynthesis of SeNPs using Alborzia kermanshahica and chitosan (CS) as stabilizers has been developed. The SeNPs synthesis was performed at different cyanobacterial cultivation conditions, including control (without magnetic field) and magnetic fields of 30 mT and 60 mT. The SeNPs were characterized by uv-visible spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), Dynamic light scattering (DLS), zeta potential, and TEM. In addition, the antibacterial activity, inhibition of bacterial growth, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC), as well as the antifungal activity and cytotoxicity of SeNPs, were performed. The results of uv-visible spectrometry, DLS, and zeta potential showed that 60 mT had the highest value regarding the adsorption, size, and stabilization in compared to the control. FTIR spectroscopy results showed consistent spectra, but the increased intensity of peaks indicates an increase in bond number after exposure to 30 mT and 60 mT. The results of the antibacterial activity and the inhibition zone diameter of synthesized nanoparticles showed that Staphylococcus aureus was more sensitive to nanoparticles produced under 60 mT. Se-NPs produced by Alborzia kermanshahica cultured under a 60 mT magnetic field exhibit potent antimicrobial and anticancer properties, making them a promising natural agent for use in the pharmaceutical and biomedical industries.