Background/Objectives: Rheumatoid arthritis is an autoimmune disease that induces joint deformity and disability. There are great expectations for biomarkers that would predict the response to treatment. CHI3L1 and CHI3L2 are chitinase-like proteins (CLPs) which lack enzymatic activity. CHI3L1 is expressed by a variety of cells, while reports on CHI3L2 are limited. The aim of the current study is to evaluate gene and protein CHI3L1 and CHI3L2 expressions before and after treatment of patients with RA and to search for correlations with ultrasonography and conventional laboratory parameters. Methods: Twenty-four newly diagnosed RA patients (19 females and five males) were enrolled in the study. Fourteen patients were treated with tofacitinib (TOFA) and 10 patients with methotrexate (MTX) for twenty-four weeks. Conventional biochemical and immunological markers were examined at the start of the treatment and after the follow-up period. The activity of RA was assessed via the Disease Activity Score 28 (DAS28). Gene expression and protein analysis were performed. Results: Ultrasonographic and clinical laboratory parameters showed improvement after therapy in both groups. A decrease in plasma levels of CHI3L1 (p = 0.04 *) and CHI3L2 (p = 0.03 *) were found after treatment with TOFA. No changes in either protein level were detected after MTX therapy, nor were any differences discovered in the gene expression of CLPs after treatment with both therapeutics. Strong correlations between CRP, GUS7 and CLPs were also established. Conclusions: The similar dynamics of CLPs expression in naïve RA patients and their distinct interplay with disease-related parameters after therapy suggest that both proteins may display different functions in RA pathophysiology.

Photodynamic therapy (PDT) is an established light-based treatment modality that relies on the activation of photosensitizers to generate reactive oxygen species (ROS) and induce localized cytotoxicity. In recent years, microalgae have emerged as a promising and sustainable source of natural photosensitizers due to their ability to biosynthesize structurally diverse pigments with strong light-harvesting capacity. This review provides a comprehensive, application-oriented analysis of microalgae-derived photosensitizers, focusing on chlorophylls and their derivatives, carotenoids, and phycobiliproteins. Particular attention is given to analytical strategies for pigment extraction, purification, and characterization, as well as to photophysical properties, subcellular localization, and ROS-mediated mechanisms underlying photodynamic activity. Recent advances in the chemical modification of algal pigments, including chlorin-based derivatives and 5-aminolevulinic acid–related systems, are critically discussed in relation to structure–activity relationships and translational performance. The accumulated evidence demonstrates that microalgae-derived pigments and their synthetic analogues can achieve efficient singlet oxygen generation, organelle-specific phototoxicity, and favorable therapeutic selectivity. Taken together, these findings highlight microalgae as a renewable and versatile platform for developing next-generation photosensitizers with broad biomedical potential in oncology, dermatology, and antimicrobial photodynamic therapy.

Tropical almond tree (Terminalia catappa L.), belonging to the Combretaceae family, is an unfurling tree with different edible parts. This review discussed the nutritional content, ethnopharmacological applications, main bioactive components, biological effects and economic potential of T. catappa. T. catappa shows essential applications in medicine, cosmetics and pharmaceutics. The nutritional values of T. catappa are associated with its contents of carbohydrates, minerals, proteins, lipids, vitamins and amino acids. It is used in many ethnopharmacological applications, including a heart stimulator, anti-diarrhoeal, bactericidal, anti-parasitic and anti-stress. T. catappa is used to treat angina pectoris, asthma attacks and bronchitis. The main reported biological activities for T. catappa were antioxidant, antidiabetic, anti-atherosclerosis, antitumor, antimicrobial, anthelmintic, antimalaria, hepatoprotective, insecticidal, anti-inflammatory and antihyperlipidemic activities. The main bioactive components reported in T. catappa encompassed phenolic compounds, alkaloids, diterpenes, fatty acids, galloyl glucose and derivatives, steroids and coumarins. T. catappa shows great economic opportunities which need to be expanded and diversified, taking into account its sustainability.

Background: Cannabidiol (CBD) is a major non-psychoactive phytocannabinoid that exerts multiple biological effects in the body. It has been shown to exert anti-cancer effects in a variety of cancer cells, including acute lymphoblastic leukemia of pre-T cell origin (T-ALL), a highly aggressive hematological malignancy. However, the mechanisms underlying CBD’s anti-cancer effects are not fully understood. Furthermore, cancer cells abundantly express surface CD47, which is a negative regulator of phagocytosis and linked with cell survival/death. Little is known about CBD effects on the expression of CD47 in T-ALL cells. The objectives of this study were to address these issues. Methods: Studies were conducted in vitro using Jurkat cells and human peripheral blood mononuclear cells in different culture conditions, CBD concentrations, and in the presence or absence of different reagents. Results: CBD downregulates CD47 expression and induces apoptosis in Jurkat cells. Similar biological effects of CBD were also observed in primary human CD4+ T cells, albeit at reduced levels. The CBD’s effects on CD47 expression and apoptosis were not rescued by a cannabinoid receptor (CBR)-2 agonist, a CBR-2 antagonist, or an anion channel blocker. However, these effects on CD47 expression and apoptosis were significantly rescued by a Voltage-Dependent Anion Channel (VDAC)-1 oligomerization inhibitor. Conclusions: Overall, we conclude that CBD downregulates CD47 expression and induces apoptosis involving VDAC-1 oligomerization. Furthermore, they also suggest that CBD’s pro-apoptotic effects on primary human T cells should also be monitored if it is used as an anti-cancer adjuvant or neo-adjuvant therapeutic in cancer patients.

Background/Objectives: Necroptosis is a critical process in the pathogenesis of myocardial ischemia–reperfusion injury (MIRI). Tilianin (Til), a natural flavonoid glycoside derived from Dracocephalum moldavica L., exhibits significant therapeutic potential in cardiovascular diseases. However, its efficacy and mechanisms in mitigating necroptosis-induced MIRI remain incompletely understood. This study aimed to elucidate the molecular mechanisms by which Til regulates cardiomyocyte necroptosis to alleviate MIRI. Methods: A rat model of MIRI was established by ligating the left anterior descending coronary artery. Necroptosis in H9c2 cardiomyocytes was induced by oxygen–glucose deprivation/reoxygenation (H/R) combined with Z-VAD-FMK. Myocardial infarct size was assessed using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Histopathological injury in cardiac tissue was examined by hematoxylin–eosin (HE) staining. Fluorescent probes were used to detect reactive oxygen species (ROS) and mitochondria. The molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) method was used to predict the binding energy between Til and RIP3. Furthermore, RIP3 overexpression and knockdown, along with inhibition of the downstream protein CaMKII, were used to further investigate the mechanism. Results: Til treatment significantly reduced MIRI in rats, decreased myocardial infarct size, histopathological injury, and regulated myocardial enzyme levels. Til pretreatment effectively inhibited necroptosis in H9c2 cells induced by H/R and Z-VAD-FMK, as evidenced by reduced necroptosis rates, decreased inflammatory cytokine release, improved mitochondrial function, and suppressed phosphorylation of the necroptosis marker MLKL. Molecular docking and dynamics simulation demonstrated stable binding of Til to RIP3, which was verified through Western blot. The protective effects of Til on necroptosis were reversed by RIP3 overexpression. Furthermore, the CaMKII inhibitor KN93 abolished Til’s effect on mitochondria. Conclusions: Til alleviates MIRI by targeting RIP3 to inhibit the necroptosis pathway and mPTP opening. These findings provide a new therapeutic strategy for MIRI and necroptosis-related diseases.

Background: Recently, compounds such as pyrimidine, pyridazine, 1,2,4-triazepine, 1,3,4,6-oxatriazepine, pyridazino[1,2-a]pyrimidine, and pyridazino[1,2-c] pyrimidine, as well as their derivatives, have attracted attention due to their diverse biological activities. Objective: This study focuses on the synthesis of new heterocyclic compounds that feature a seven-membered ring, including pyridazinopyrimido[2,1-c] [1,2,4]triazepine-tetraones (4), pyridazinopyrimidotriazepine-triones (5–8), aminopyri-dazinopyrimido[2,1-c][1,2,4]triazepine-tetraone (9), and 6-amino-8-imino-pyridazino pyrimido[2,1-c] [1,2,4]triazepine-trione (10). These new compounds were synthesized starting from 1-(4-oxo-1,4-dihydropyrimidine)-1,2-dihydropyridazine-3,6-dione (3) and were then evaluated for their antimicrobial activity. Methods: A new series of pyridazino[1,2-a]pyrimido[2,1-c][1,2,4]triazepines and 1,3,4,6-oxatriazepines were synthesized using modern techniques and advanced technology, achieving yields between 72% and 90%. Results: All new compounds were confirmed through IR, 1H NMR, 13C NMR, and mass spectroscopy (MS) and tested for in vitro antimicrobial activity. Compounds (8-10) exhibited excellent antimicrobial activity. Computational analysis provided a comprehensive evaluation of the broad-spectrum inhibitory potential of four lead compounds (6, 8, 9, and 10) against key microbial and fungal targets. These compounds demonstrated consistently superior binding affinities compared to control drugs cefotaxime and nystatin across a range of enzymes essential for pathogen viability and virulence. Conclusions: The structure–activity relationship (SAR) study established a correlation between the tested compounds and their antimicrobial activity. Molecular docking analysis indicated that the in silico results strongly suggest that compounds (6, 8, 9, and 10) are promising multi-target agents capable of disrupting essential bacterial processes and critical fungal pathways, making them excellent candidates for the development of novel antimicrobial therapeutics. These consistent findings support the conclusion that both practical and theoretical studies of the new compounds align with their antimicrobial effectiveness.

In the original publication [...]

Background: A benzotriazole is a heterocycle frequently used in medicinal chemistry to obtain potent drug candidates, including anticancer agents. Nonetheless, the available literature lacks a comprehensive review of the in vitro and in vivo studies regarding these derivatives. Thus, our study aims to review the preclinical evidence on benzotriazole derivatives that showed potential as anticancer candidates, focusing on the cytotoxicity, mechanisms of action, structure–activity relationship, and methodological rigor of the included studies. Methods: We searched PubMed, Scopus, and Web of Science and included 41 studies in our analysis following the selection process. Additionally, we assessed the risk of bias using the QUIN tool for in vitro and the SYRCLE tool for in vivo studies in order to assess the methodological rigor of the included studies. Results: The benzotriazole derivatives were classified according to their structure in four classes, namely N-derivatives, C-derivatives, fused derivatives, and organometallic compounds. The in vitro results showed that certain derivatives, such as halogen, alkyl-aryl, or natural-base hybrids, can have superior cytotoxicity compared to parent molecules, exerted through multiple mechanisms, such as apoptosis and cell cycle arrest. Additionally, the in vivo analysis highlighted that benzotriazole derivatives can reduce tumor mass in a dose-dependent manner, with only a slight degree of hepatotoxicity reported in one case. However, histopathological data were generally absent or limited and based on a very limited number of in vivo studies. Conclusions: Overall, benzotriazole derivatives remain promising candidates for cancer treatment. However, limited mechanistic and toxicity data, as well as the moderate risk of bias identified across studies, may limit our assessment. Therefore, future studies should employ more rigorous methodologies and explore the underlying anticancer and toxicity mechanisms to fully assess the therapeutic potential of benzotriazole derivatives.

Background/Objectives: This study aimed to perform a comparative analysis of the original Viagra® product and sildenafil-containing tablets obtained from illegal sources (the darknet). Specifically, the analyzed material consisted of samples seized by Polish law enforcement authorities from unverified vendors operating within the Central European darknet market. The study utilized thermal methods, specifically Thermogravimetry (TG), Derivative Thermogravimetry (DTG), and calculated Differential Thermal Analysis (c-DTA), as well as colorimetric analysis based on the International Commission on Illumination (CIE) L*a*b* system. Methods: Thermal analyses enabled the assessment of the thermal stability of the tested samples, identification of characteristic stages of thermal decomposition, and determination of differences in thermal behavior between the pure substance, the original preparation, and darknet samples. In turn, color measurements in the CIE L*a*b* space allowed for an objective comparison of tablet appearance and determination of the degree of color similarity to the original product. Results: The obtained results showed that only a few samples (V1, V3, V4, V6, V8) exhibited features similar to the original Viagra®, both in terms of thermal profile and color. Most of the tested tablets were characterized by significant variability in physicochemical properties, indicating a lack of quality control and inconsistency in formulation. Samples V2 and V7 deviated particularly strongly—both thermally and visually—suggesting that they might not contain the original active substance or contained it in a different chemical form. Conclusions: The use of combined thermal and colorimetric methods proved to be an effective tool in the identification of counterfeit pharmaceutical products, enabling simultaneous evaluation of their composition and authenticity. The results confirm the validity of employing integrated physicochemical analyses for the detection of falsified medicines present on the illegal market.

Background/Objectives: This study aimed to evaluate the pharmacokinetics (PK), effectiveness, and safety of the direct interleukin-6 (IL-6) inhibitor olokizumab (OKZ) in adolescent patients with active polyarticular juvenile idiopathic arthritis (pJIA) who had an inadequate response or intolerance to methotrexate (MTX). Methods: We analyzed results from an open-label, single-arm trial of OKZ therapy at a dose of 64 mg every 4 weeks for 24 weeks. We evaluated pharmacokinetic (PK) parameters, clinical effectiveness, serum C-reactive protein (CRP) dynamics, and adverse events (AEs). Results: Sixteen patients were included in the study, of whom 13 (81.2%) received OKZ through Week 24. The PK profile was consistent with observations in adults with rheumatoid arthritis (RA). By Week 16, 12 (80%) patients achieved an ACRpedi30 response, 11 (73.3%) achieved an ACRpedi50 response, and 2 (13.3%) reached inactive disease status. This response was sustained through Week 24, and no disease flares were observed. A trend toward a better response was noted among patients with baseline CRP > 10 mg/L, higher baseline IL-6, and those naïve to biologic DMARDs. Twelve patients (75.0%) experienced twenty-three mild or moderate AEs. Infections were the most frequent AEs (in 6 patients, 37.5%). No serious AEs or deaths occurred. Conclusions: OKZ treatment reduced pJIA disease activity and was well tolerated. The safety profile was consistent with that of other IL-6 inhibitors, and the PK profile matched that seen in adult RA patients.