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Background: It is well known that periodontitis affects the gums and surrounding connective tissue. The chronic inflammatory response induced by bacteria in the gingival tissue leads to the loss of the collagen connection between the tooth and the bone and ultimately to bone loss.

Methods: In this context, the aim of this research was the obtaining and characterization of a drug release supports in the form of sponges based on collagen, hyaluronic acid as a support and metronidazole as an antibiotic for the treatment of periodontitis. The sponges were characterized by FT-IR spectroscopy, water uptake, contact angle, SEM microscopy, in vitro metronidazole release analysis from sponges and data modeling.

Results: The results showed that all the sponges had a porous structure with interconnected pores, the pore sizes being influenced by hyaluronic acid and metronidazole; the spongious structure became much more dense for samples with metronidazole content. All metronidazole-loaded sponges showed good surface wettability and an adequate swelling capacity for a suitable antimicrobial release at the periodontal pocket. The porous structures allow a controlled release, fast in the first hour, essential to control the initial microbial load at the periodontal level, which continues slowly in the following hours to ensure an effective treatment of periodontitis.

Conclusions: Correlating all physical-chemical and bio-pharmaceutical results obtained, a promising solution for periodontitis treatment could be a met-ronidazole-collagen-hyaluronic system consisting of 1% collagen, 1.5% metronidazole and 0.8% hyaluronic acid, and in vitro and in vivo tests are recommended to continue studies.

Background: This study aims to explore the protective role of JB-V-60-a novel synthetic derivative of decur-sin-against lipopolysaccharide (LPS)-induced inflammation.

Methods: We examined the effects of JB-V-60 on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human pulmonary artery endothelial cells (HPAECs). Additionally, we assessed its effects on iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in LPS-exposed mice.

Results: JB-V-60 enhanced HO-1 levels, inhibited NF-κB activation, reduced COX-2/PGE2 and iNOS/NO concentra-tions, and lowered phosphorylation of signal transducer and activator of transcription 1. It also promoted the translocation of Nrf2 into the nucleus, allowing its binding to antioxidant response elements and resulting in reduced IL-1β in LPS-stimulated HPAECs. The reduction in iNOS/NO levels by JB-V-60 was reversed when HO-1 was inhibited via RNAi. In the animal model, JB-V-60 sig-nificantly decreased iNOS expression in lung tissues and TNF-α levels in bronchoalveolar lavage fluid.

Conclusions: These findings highlight the anti-inflammatory effects of JB-V-60 and its potential as a treat-ment for inflammatory disorders.

Background: Plants have long been recognized for their potential to influence neurological health, with both neuroprotective and neurotoxic properties. This review explores the dual nature of plant-derived compounds and their impact on the human brain.

Discussion: Numerous studies have highlighted the neuroprotective effects of various phytoconstituents, such as those found in Ginkgo biloba, Centella asiatica, Panax ginseng, Withania somnifera, and Curcuma longa. The neuroprotective compounds have demonstrated antioxidant, anti-inflammatory, and cognitive-enhancing properties, making them promising candidates for combating neurodegenerative diseases and improving brain function. Polyphenolic compounds, triterpenic acids, and specific phytocompounds like the ones from EGb 761 extract have shown interactions with key enzymes and receptors in the brain, leading to neuroprotective outcomes. However, this review also acknowledges the neurotoxic potential of certain plants, such as the Veratrum species, which contains steroidal alkaloids that can cause DNA damage and disrupt neurological function, or Atropa belladonna, which interfere with the normal functioning of the cholinergic system in the body, leading to a range of symptoms associated with anticholinergic toxicity.

Conslusions: This review also emphasizes the need for further research to elucidate the complex mechanisms underlying the neuroprotective and neurotoxic effects of plant-derived compounds, as well as to identify novel phytoconstituents with therapeutic potential. Understanding the complex relationship between plants and the human brain is crucial for harnessing the benefits of neuroprotective compounds while mitigating the risks associated with neurotoxic substances. This review provides a comprehensive overview of the knowledge on the neurological properties of plants and highlights the importance of continued research in this field for the development of novel therapeutic strategies targeting brain health and neurological disorders.

ADCs have emerged as a promising class of therapeutics, combining the targeting specificity of monoclonal antibodies with the cytotoxic potency of small-molecule drugs. Although the majority of approved ADCs are still based on microtubule binder payloads, the recent success of topoisomerase I inhibitors has revitalized interest in the identification of novel agents overcoming present limitations in the field including narrow therapeutic window and chemoresistance. The success of DNA binders as payload for ADCs has been very limited, up to now, due, among other factors, to high hydrophobicity and planar chemical structures resulting in most cases in ADCs with a strong tendency to aggregate, poor plasma stability, and limited therapeutic index. Some of these molecules, however, continue to be of interest due to their favorable properties in terms of cytotoxic potency even in chemoresistant settings, bystander and immunogenic cell death effects, and known combinability with approved drugs. We critically evaluated several clinically tested ADCs containing DNA binders, focusing on payload physicochemical properties, cytotoxic potency, and obtained clinical results. Our analysis suggests that further exploration of certain chemical classes, specifically anthracyclines and duocarmycins, based on the optimization of physicochemical parameters, reduction of cytotoxic potency, and careful design of targeting molecules is warranted. This approach will possibly result in a novel generation of payloads overcoming the limitations of clinically validated ADCs.

The public is increasingly reporting using cannabis for anxiety relief. Both cannabis use and the endocannabinoid system have been connected with anxiety relief/anxiolytic properties, but these relationships are complex, and the underlying mechanisms for them are unclear. Background/Objectives: Work is needed to understand how the endocannabinoid system, including the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may be impacted by the main constituents of cannabis, Δ9-tetrahydrocannabinol (THC), and cannabidiol (CBD). Methods: The current study examined how the ab libitum use of products differing in THC and CBD affected AEA and 2-AG among 292 individuals randomly assigned to THC-dominant use (N = 92), CBD-dominant use (N = 97), THC + CBD use (N = 74), or non-use (N = 29). Results: The findings suggest that AEA levels do not change differently based on 4 weeks of cannabis use or by cannabinoid content, as AEA similarly increased across all conditions from study weeks 2 to 4. In contrast, AEA decreased at an acute administration session with product conditions containing any THC having greater AEA levels on average than the non-use condition. With regard to 2-AG, its levels appeared to primarily be affected by THC-dominant use, both acutely and over 4 weeks, when controlling for baseline cannabis use and examining study product use frequency among use conditions. Conclusions: Overall, the results continue to shed light on the complicated relationship between cannabinoid content and endocannabinoid production, and highlight the need for continued research on their interplay in human subjects.

Background/Objectives: The role of the gut microbiome in the development and progression of many diseases has received increased attention in recent years. Boron, a trace mineral found in dietary sources, has attracted interest due to its unique electron depletion and coordination characteristics in chemistry, as well as its potential role in modulating the gut microbiota. This study investigates the effects of inorganic boron derivatives on the gut microbiota of mice. Methods: For three weeks, boric acid (BA), sodium pentaborate pentahydrate (NaB), and sodium perborate tetrahydrate (SPT) were dissolved (200 mg/kg each) in drinking water and administered to wild-type BALB/c mice. The composition of the gut microbiota was analyzed to determine the impact of these treatments. Results: The administration of BA significantly altered the composition of the gut microbiota, resulting in a rise in advantageous species such as Barnesiella and Alistipes. Additionally, there was a decrease in some taxa associated with inflammation and illness, such as Clostridium XIVb and Bilophila. Notable increases in genera like Treponema and Catellicoccus were observed, suggesting the potential of boron compounds to enrich microbial communities with unique metabolic functions. Conclusions: These findings indicate that boron compounds may have the potential to influence gut microbiota composition positively, offering potential prebiotic effects. Further research with additional analyses is necessary to fully understand the interaction between boron and microbiota and to explore the possibility of their use as prebiotic agents in clinical settings.

Evaluation of pharmacokinetic properties is a significant step at the early stages of drug development. In this study, an in vitro evaluation of the pharmacokinetic properties of five newly synthesized compounds was performed. These compounds belong to N-hydroxyurea and hydroxamic acid derivatives and analogs of NSAIDs indomethacin, flurbiprofen, diclofenac, ibuprofen, and naproxen (compounds 1, 2, 3, 11, and 12, respectively) with dual COX-2 and 5-LOX inhibitory activity. Two in vitro methods (biopartitioning micellar chromatography (BMC) and PAMPA) were used to evaluate passive gastrointestinal absorption, while high-performance affinity chromatography (HPAC) and differential pulse voltammetry (DPV) were used to evaluate binding to human serum albumin (HSA). The introduction of N-hydroxyurea and hydroxamic acid groups into the structure of NSAIDs decreases both expected passive gastrointestinal absorption (BMC k values were from 3.02 to 9.50, while for NSAIDs were from 5.29 to 13.36; PAMPA -logPe values were between 3.81 and 4.76, while for NSAIDs were ≤3.46) and HSA binding (HPAC logk values were from 2.03 to 9.54, while for NSAIDs were ≥11.03; DPV peak potential shifts were between 7 and 34, while for NSAIDs were ≥54). Structural modifications of all tested compounds that increase lipophilicity could be considered to enhance their passive gastrointestinal absorption. Considering lower expected HSA binding and higher lipophilicity of tested compounds compared to corresponding NSAIDs, it can be expected that the volume of distribution of compounds 1, 2, 3, 11, and 12 will be higher. Reduced HSA binding may also decrease interactions with other drugs in comparison to corresponding NSAIDs. All tested compounds showed significant microsomal instability (25.07-58.44% decrease in concentration) in comparison to indomethacin (14.47%) and diclofenac (20.99%).

Background/Objectives: Annona squamosa is used in folk medicine to treat pain and arthritis. Palmatine is an alkaloid isolated from several plants, including A. squamosa leaves. The aim of the present study was to investigate the analgesic, anti-arthritic, and anti-inflammatory potential of the methanolic extract of A. squamosa (EMAS) and palmatine. Methods: The chemical profile of EMAS was evaluated by ultra high-performance liquid chromatography with electrospray ionization coupled to mass spectrometry (UHPLC-ESI/MS). EMAS and palmatine were evaluated in carrageenan-induced pleurisy, zymosan-induced joint inflammation, formalin-induced nociception, and tumor necrosis factor (TNF)-induced mechanical hyperalgesia in experimental models in mice. A cytotoxicity test of EMAS and palmatine was performed using a methylthiazolidiphenyl-tetrazolium (MTT) bromide assay. Results: The analysis of the chemical profile of the extract showed the presence of palmatine, liriodenine, and anonaine. Oral administration of EMAS and palmatine significantly reduced leukocyte migration and oxide nitric production in the carrageenan-induced pleurisy model. EMAS and palmatine reduced mechanical hyperalgesia, leukocyte migration, and edema formation in the joint inflammation induced by zymosan. In the formalin test, palmatine was effective against the second-phase nociceptive response, mechanical hyperalgesia, and cold allodynia. In addition, palmatine reduced mechanical hyperalgesia induced by TNF. EMAS and palmatine did not demonstrate cytotoxicity. Conclusions: The present study showed that A. squamosa and palmatine are analgesic and anti-inflammatory agents, and that the anti-hyperalgesic properties of palmatine may involve the TNF pathway. Palmatine may be one of the compounds responsible for the anti-hyperalgesic and/or anti-arthritic properties of this medicinal plant.

Background/Objectives: Parenteral nutrition (PN) is used when enteral feeding is not possible. It is a complex mixture of nutrients that must meet a patient's needs but can face stability issues, such as lipid emulsion destabilisation and precipitate formation. Stability studies are complex, and the methodologies used are very varied in the literature. In addition, many studies are outdated and use outdated components. This study conducts a stability analysis of PN solutions using optical microscopy. Methods: Samples were prepared according to clinical practice standards and previous studies. We used a counting chamber for optical microscopic observations and different storage conditions (RT, 4 °C 1-14 days). Results: Precipitates larger than 5 µm were found in 8 out of 14 samples after 14 days of storage at room temperature, and none were observed in refrigerated samples. More lipid globules larger than 5 µm were detected in samples stored at room temperature than in those stored in a refrigerator after 14 days. Additionally, the number of large globules generally increased from day 1 to day 14 in most samples. Conclusions: The observed precipitates were probably calcium oxalate crystals, the formation of which is possible in PN but is not expected under the usual storage conditions in a hospital environment. Prolonged storage time and storage at room temperature increases the formation of these precipitates. These findings highlight the importance of using filters during both the preparation and administration of PN to prevent large particles from reaching patients.

Background/Objectives: This study investigates the development of 3D chitosan-x-cobalt ferrite scaffolds (x = 5, 7.5, and 10 wt%) with interconnected porosity for potential biomedical applications. The objective was to evaluate the effects of magnetic particle incorporation on the scaffolds' structural, mechanical, magnetic, and biological properties, specifically focusing on their biocompatibility and antimicrobial performance. Methods: Scaffolds were synthesized using freeze-drying, while cobalt ferrite nanoparticles were produced via a pilot-scale combustion reaction. The scaffolds were characterized for their physical and chemical properties, including porosity, swelling, and mechanical strength. Hydrophilicity was assessed through contact angle measurements. Antimicrobial efficacy was evaluated using time kill kinetics and agar diffusion assays, and biocompatibility was confirmed through cytotoxicity tests. Results: The incorporation of cobalt ferrite increased magnetic responsiveness, altered porosity profiles, and influenced swelling, biodegradation, and compressive strength, with a maximum value of 87 kPa at 7.5 wt% ferrite content. The scaffolds maintained non-toxicity and demonstrated bactericidal activity. The optimal concentration for achieving a balance between structural integrity and biological performance was found at 7.5 wt% cobalt ferrite. Conclusions: These findings suggest that magnetic chitosan-cobalt ferrite scaffolds possess significant potential for use in biomedical applications, including tissue regeneration and advanced healing therapies. The incorporation of magnetic properties enhances both the structural and biological functionalities, presenting promising opportunities for innovative therapeutic approaches in reconstructive procedures.