Investigation of the molecular mechanisms underlying the anti-inflammatory and antitumour effects of isorhapontigenin: Insights from in vitro and in vivo studies.

Isorhapontigenin (ISO), a naturally-occurring stilbene derivative, has garnered significant attention due to its potent anticancer and anti-inflammatory properties. This review synthesizes current knowledge regarding the mechanisms of action, efficacy, and potential therapeutic applications of Isorhapontigenin acquired in vitro and in vivo. It systematically analyzes its effects on various cancer cell lines, tumor models, and inflammatory conditions, examining its impact on cell proliferation, apoptosis, metastasis, and inflammatory mediators. In vitro studies reveal that Isorhapontigenin induces cell cycle arrest, promotes apoptosis, and inhibits cancer cell migration through modulation of key signaling pathways, including EGFR-PI3K-Akt and NF-κB. It also demonstrates potent antioxidant and anti-inflammatory effects by enhancing Nrf2 signaling and suppressing pro-inflammatory cytokine production. These findings are corroborated by in vivo studies confirming its ability to inhibit tumor growth in xenograft models and attenuate inflammatory responses in various disease models. Notably, Isorhapontigenin exhibits superior pharmacokinetic profiles then resveratrol, with higher oral bioavailability. Isorhapontigenin demonstrates multi-target actions, including epigenetic modulation through microRNA regulation, which highlight its potential as a versatile therapeutic agent. This review also identifies current limitations in Isorhapontigenin research that require further investigation. Overall, Isorhapontigenin offers promise as a multi-faceted compound for the treatment of cancer, inflammatory diseases, and metabolic disorders, providing a solid foundation for future research and potential clinical applications.

Anti-Inflammatory and Anticancer Effects of Anthocyanins in In Vitro and In Vivo Studies.

Anthocyanins, a class of flavonoid compounds responsible for the vibrant colors of many fruits and vegetables, have received considerable attention in recent years due to their potential health benefits. This review, focusing on evidence from both in vitro and in vivo studies, provides a comprehensive overview of the current state of knowledge regarding the health-promoting properties of anthocyanins. The chemical structure and diversity of anthocyanins, their bioavailability, and their mechanisms of action at the cellular and molecular level are examined. Research on the antioxidant, anti-inflammatory, anticancer, and neuroprotective effects of anthocyanins is critically reviewed. Special emphasis is placed on the role of anthocyanins in the prevention and treatment of chronic diseases such as cardiovascular diseases, diabetes, and neurodegenerative diseases. This review also discusses the challenges of translating in vitro findings to in vivo and highlights the importance of considering dose, bioavailability, and metabolism when assessing the therapeutic potential of anthocyanins. This review concludes with the identification of gaps in current research and suggestions for future directions for anthocyanin studies, including the need for more long-term clinical trials and investigations into potential synergistic effects with other phytochemicals. This comprehensive analysis highlights the promising role of anthocyanins in promoting human health and provides valuable insights for researchers, health professionals, and the nutraceutical industry. This study provides new insights, as it comprehensively investigates the dual anti-inflammatory and anticancer effects of anthocyanins in both in vitro and in vivo models. By uncovering the biological properties of anthocyanins from a variety of natural sources, this research not only expands our knowledge of the action of these compounds at the cellular level, but also enhances their clinical relevance through in vivo validation. Furthermore, the innovative use of anthocyanins may lead to important advances in their therapeutic application in the future.

Coronaridine congeners induce anticonvulsant activity in rodents by hippocampal mechanisms involving mainly potentiation of GABAA receptors.

The coronaridine congeners catharanthine and 18-methoxycoronaridine (18-MC) display sedative, anxiolytic, and antidepressant properties by acting on mechanisms involving GABAergic and/or monoaminergic transmissions. Here, we expanded their pharmacological properties by studying their anticonvulsant activity in male and female mice using the pentylenetetrazole (PTZ)-induced seizure test. To determine potential neurochemical mechanisms, the effect of congeners on monoamine content and kainic acid (KA)-induced epileptiform discharge was studied in the hippocampus. The behavioral results showed that coronaridine congeners induce acute anticonvulsant activity in a dose-dependent but sex-independent manner. Repeated treatment with a subthreshold dose (20 mg/kg) of each congener produced anticonvulsant activity in a sex-independent manner, but was significantly higher in male mice when compared to its acute effect. Using a behaviourally relevant regimen, we found that PTZ increased dopamine metabolites and serotonin tissue content. Coronaridine congeners, which induced distinct effects on monoamines, blunted the effect of PTZ instead of potentiating it, suggesting the existence of another mechanism in their anticonvulsant activity. The electrophysiological results indicated that both congeners inhibit KA-induced epileptiform discharges in hippocampal slices. A key aspect of this study is that the activity of both congeners was observed only in the presence of GABA, supporting the notion that hippocampal GABAAR potentiation plays an important role. Our study showed that coronaridine congeners induce acute anticonvulsant activity in a sex-independent manner. However, a comparatively higher susceptibility was observed in male mice after repeated treatment. The underlying hippocampal mechanisms mainly involve GABAAR potentiation, whereas monoamines play a minor role in the anticonvulsive action.

Hemorrhagic Cysts in the Pancreas: Risk Factors, Treatment, and Outcomes - Insights from a Single-Center Study.

BACKGROUND Hemorrhagic cysts are rarely discussed subtypes of pancreatic pseudocysts that occur in about 10% of these cases. They are caused by erosion of the walls of neighboring vessels by extravasated proteolytic pancreatic enzymes. A retrospective analysis was performed to clinically characterize risk factors, treatment, and outcome in patients with hemorrhagic cysts of the pancreas. MATERIAL AND METHODS The retrospective study included patients from the Department of Digestive Tract Surgery in Katowice, Poland, who were treated surgically for a pancreatic hemorrhagic cyst from January 2016 to November 2022. We gathered and assessed data on cyst etiology, symptoms, imaging examinations, risk factors, time, type, and complications of surgery. RESULTS The main symptom was abdominal pain, noted in 5 (62.5%) patients. The most common etiology of cyst was acute pancreatitis, which occurred in 5 patients (62.5%). The most common localization was the tail of pancreas, found in 3 patients (36.5%). The largest dimension of the cyst was 98±68 (30-200) mm. Every patient needed surgical intervention. Patients underwent distal pancreatectomy (n=3) or marsupialization (n=5). One (12.5%) postoperative complication was observed, while mortality was 0%. CONCLUSIONS Hemorrhagic cyst is a life-threatening complication of pancreatitis requiring immediate treatment. In most cases, open surgery is the treatment of choice. Despite the continuous development of minimally invasive techniques, surgical treatment remains the only effective treatment method. Depending on the cyst localization and technical possibilities, pancreatectomy or marsupialization can be applied, and both of them have low complication and mortality rates.

Exploring the Anticancer Potential of Semisynthetic Derivatives of 7α-Acetoxy-6ß-hydroxyroyleanone from Plectranthus sp.: An In Silico Approach.

The diterpene 7α-acetoxy-6ß-hydroxyroyleanone isolated from Plectranthus grandidentatus demonstrates promising antibacterial, anti-inflammatory and anticancer properties. However, its bioactivity may be enhanced via strategic structural modifications of such natural products through semisynthesis. The anticancer potential of 7α-acetoxy-6ß-hydroxyroyleanone and five derivatives was analyzed in silico via the prediction of chemicals absorption, distribution, metabolism, excretion, and toxicity (ADMET), quantum mechanical calculations, molecular docking and molecular dynamic simulation. The protein targets included regulators of apoptosis and cell proliferation. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Derivatives 7α-acetoxy-6ß-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6ß-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone achieved high predicted binding affinities towards their respective protein panels, with stable molecular dynamics trajectories. Both compounds demonstrated favorable ADMET parameters and toxicity profiles. Their stability and reactivity were confirmed via geometry optimization. Network analysis revealed their involvement in cancer-related pathways. Our findings justify the inclusion of 7α-acetoxy-6ß-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6ß-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone in in vitro analyses as prospective anticancer agents. Our binding mode analysis and stability simulations indicate their potential as selective inhibitors. The data will guide studies into their structure optimization, enhancing efficacy and drug-likeness.

Anticancer Effects of Abietane Diterpene 7α-Acetoxy-6ß-hydroxyroyleanone from Plectranthus grandidentatus and Its Semi-Synthetic Analogs: An In Silico Computational Approach.

The abietane diterpenoid 7α-acetoxy-6ß-hydroxyroyleanone (Roy) isolated from Plectranthus grandidentatus demonstrates cytotoxicity across numerous cancer cell lines. To potentiate anticancer attributes, a series of semi-synthetic Roy derivatives were generated and examined computationally. ADMET predictions were used to evaluate drug-likeness and toxicity risks. The antineoplastic potential was quantified by PASS. The DFT models were used to assess their reactivity and stability. Molecular docking determined cancer-related protein binding. MS simulations examined ligand-protein stability. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Favorable ADME attributes and acceptable toxicity profiles were determined for all compounds. Strong anticancer potential was shown across derivatives (Pa 0.819-0.879). Strategic modifications altered HOMO-LUMO gaps (3.39-3.79 eV) and global reactivity indices. Favorable binding was revealed against cyclin-dependent kinases, BCL-2, caspases, receptor tyrosine kinases, and p53. The ligand exhibited a stable binding pose in MD simulations. Network analysis revealed involvement in cancer-related pathways. In silico evaluations predicted Roy and derivatives as effective molecules with anticancer properties. Experimental progress is warranted to realize their chemotherapeutic potential.

Halimane Derivatives from Plectranthus ornatus Codd. as Novel Anti-cancer Agents.

The Plectranthus genus is often cited for its medicinal properties. Plectranthus ornatus Codd. is traditionally used in Africa for the treatment of gastric and liver diseases and their leaves are used for their antibiotic action. The main constituent of P. ornatus is the halimane compound, 11 R∗-acetoxyhalima-5,13E-dien-15-oic acid (Hal), described for its antimicrobial and anticancer properties. The objective of this work was to improve the activity of the halimane lead molecule. Further physiochemical characterisation was performed on Hal. To the best of our knowledge, this work constitutes the first published data of the absolute configurations by SCXRD and thermal stability of Hal. Using Hal, reactions with different amines were carried out to afford novel semi-synthetic derivatives and their structural elucidation was completed. The cytotoxicity of the derivatives was assessed against three leukaemia cancer cell lines (CCRF-CEM, K562 and HL-60). The antioxidant activity was investigated using H2O2-induced HGF-1 cells and their anti-inflammatory activity was studied using RT-PCR and ELISA. Our data showed that amide derivatives of Hal presented moderate cytotoxicity and more potent activity when compared to the parent molecule, giving insight into the SAR of Hal. The derivatives also displayed protection against oxidative damage to DNA. Finally, the derivatives possessed anti-inflammatory properties at the level of gene and protein expression for the cytokines IL-1ß, TNF-α and IL-6, induced by LPS in normal HGF-1 cells. Overall, our study provides useful insight into the enhanced biological activities of semi-synthetic Hal derivatives, as a starting point for novel drug formulations in cancer therapy.

The Precious Potential of the Sacred Tree Chamaecyparis obtusa (Siebold & Zucc.) Endl. as a Source of Secondary Metabolites with Broad Biological Applications.

Chamaecyparis obtusa (Siebold & Zucc.) Endl., which belongs to the Cupressaceae family, occurs naturally in North America and Asia, especially in Korea, Taiwan and Japan, where it is an evergreen, coniferous, sacred, ethnic tree. It has many useful varieties that are widespread throughout the world and grown for decorative purposes. It is most commonly used as an ornamental plant in homes, gardens or parks. It is also widely used in many areas of the economy; for example, its wood is used in architecture as well as furniture production. In addition, oil extracted from Chamaecyparis obtusa is increasingly used in cosmetology for skin care. Due to its wide economic demand, mainly in Japan, it represents the largest area of plantation forest. Despite this, it is on the red list of endangered species. Its use in ethnopharmacology has led to more and more research in recent years in an attempt to elucidate the potential mechanisms of its various biological activities, such as antimicrobial, antioxidant, anticancer, antidiabetic, antiasthmatic, anti-inflammatory, antiallergic, analgesic and central nervous system effects. It has also been shown that Chamaecyparis obtusa can be used as an insect repellent and an ingredient in plant disease treatment. This thesis provides a comprehensive review of the biological studies to date, looking at different areas of the economic fields of potential use of Chamaecyparis obtusa.

Electrospun Antimicrobial Drug Delivery Systems and Hydrogels Used for Wound Dressings.

Wounds and chronic wounds can be caused by bacterial infections and lead to discomfort in patients. To solve this problem, scientists are working to create modern wound dressings with antibacterial additives, mainly because traditional materials cannot meet the general requirements for complex wounds and cannot promote wound healing. This demand is met by material engineering, through which we can create electrospun wound dressings. Electrospun wound dressings, as well as those based on hydrogels with incorporated antibacterial compounds, can meet these requirements. This manuscript reviews recent materials used as wound dressings, discussing their formation, application, and functionalization. The focus is on presenting dressings based on electrospun materials and hydrogels. In contrast, recent advancements in wound care have highlighted the potential of thermoresponsive hydrogels as dynamic and antibacterial wound dressings. These hydrogels contain adaptable polymers that offer targeted drug delivery and show promise in managing various wound types while addressing bacterial infections. In this way, the article is intended to serve as a compendium of knowledge for researchers, medical practitioners, and biomaterials engineers, providing up-to-date information on the state of the art, possibilities of innovative solutions, and potential challenges in the area of materials used in dressings.

Biological Properties of Extracts Obtained from In Vitro Culture of Plectranthus scutellarioides in a Cell Model.

Plectranthus scutellarioides (L.) R.Br. is a medicinal plant that has long been used in traditional medicine to treat conditions such as abscesses, ulcers, and ear and eye infections. It is known to have a wide range of biological properties, such as antibacterial, antioxidant, antifungal, anti-inflammatory, anti-diabetic and anti-cancer effects. In this study, we established in vitro cultures from both the aerial parts and roots of Plectranthus scutellarioides. Subsequently, we compared the basic phytochemical profile of the obtained extracts and conducted a biological analysis to assess their potential for inducing apoptosis in breast (MCF-7) and lung (A549) cancer cells. Phytochemical analysis by HPLC-MS revealed the presence of compounds belonging to phenolic acids (ferulic, syringic, vanillic, rosmarinic, chlorogenic, caffeic, coumaric, dihydroxybenzoic acids), flavonoids (eriodyctiol and cirsimaritin), and terpenes such as 6,11,12,14,16-Pentahydroxy-3,17diacetyl-8,11,13-abietatrien-7-one, 6,11,12,14,16-Pentahydroxy-3,17-diacetyl5,8,11,13-abietatetraen-7-one, and 3,6,12-Trihydroxy-2-acetyl-8,12-abietadien7,11,14-trione. The results show that both extracts have a cytotoxic and genotoxic effect against MCF-7 and A549 cancer cells, with a different degree of sensitivity. It was also shown that both extracts can induce apoptosis by altering the expression of apoptotic genes (Bax, Bcl-2, TP53, Fas, and TNFSF10), reducing mitochondrial membrane potential, increasing ROS levels, and increasing DNA damage. In addition, it has been shown that the tested extracts can alter blood coagulation parameters. Our results indicate that extracts from in vitro cultures of Plectranthus scutellarioides aerial parts and roots have promising therapeutic application, but further research is needed to better understand the mechanisms of their action in the in vitro model.

Osteogenic Potential of Human Dental Pulp Stem Cells (hDPSCs) Growing on Poly L-Lactide-Co-Caprolactone and Hyaluronic Acid (HYAFF-11TM) Scaffolds.

Bone tissue engineering using different scaffolds is a new therapeutic approach in regenerative medicine. This study explored the osteogenic potential of human dental pulp stem cells (hDPSCs) grown on a hydrolytically modified poly(L-lactide-co-caprolactone) (PLCL) electrospun scaffold and a non-woven hyaluronic acid (HYAFF-11™) mesh. The adhesion, immunophenotype, and osteogenic differentiation of hDPSCs seeded on PLCL and HYAFF-11™ scaffolds were analyzed. The results showed that PLCL and HYAFF-11™ scaffolds significantly supported hDPSCs adhesion; however, hDPSCs' adhesion rate was significantly higher on PLCL than on HYAFF-11™. SEM analysis confirmed good adhesion of hDPSCs on both scaffolds before and after osteogenesis. Alizarin red S staining showed mineral deposits on both scaffolds after hDPSCs osteogenesis. The mRNA levels of runt-related transcription factor 2 (Runx2), collagen type I (Coll-I), osterix (Osx), osteocalcin (Ocn), osteopontin (Opn), bone sialoprotein (Bsp), and dentin sialophosphoprotein (Dspp) gene expression and their proteins were higher in hDPSCs after osteogenic differentiation on both scaffolds compared to undifferentiated hDPSCs on PLCL and HYAFF-11™. These results showed that PLCL scaffolds provide a better environment that supports hDPSCs attachment and osteogenic differentiation than HYAFF-11™. The high mRNA of early osteogenic gene expression and mineral deposits observed after hDPSCs osteogenesis on a PLCL mat indicated its better impact on hDPSCs' osteogenic potential than that of HYAFF-11™, and hDPSC/PLCL constructs might be considered in the future as an innovative approach to bone defect repair.

Glioma and post-translational modifications: A complex relationship.

Post-translational modifications (PTMs) are common covalent processes in biochemical pathways that alter protein function and activity. These modifications occur through proteolytic cleavage or attachment of modifying groups, such as phosphoryl, methyl, glycosyl, or acetyl groups, with one or more amino acid residues of a single protein. Some PTMs also present crosstalk abilities that affect both protein functionality and structure, creating new proteoforms. Any alteration in organism homeostasis may be a cancer hallmark. Cataloging PTMs and consequently, emerging proteoforms, present new therapeutic targets, approaches, and opportunities to discover additional discriminatory biomarkers in disease diagnostics. In this review, we focus on experimentally confirmed PTMs and their potential crosstalk in glioma research to introduce new opportunities for this tumor type, which emerge within the PTMomics area.

The Potential Preventive and Therapeutic Roles of NSAIDs in Prostate Cancer.

Prostate cancer (PC) is the second most common type of cancer and the leading cause of death among men worldwide. Preventing the progression of cancer after treatments such as radical prostatectomy, radiation therapy, and hormone therapy is a major concern faced by prostate cancer patients. Inflammation, which can be caused by various factors such as infections, the microbiome, obesity and a high-fat diet, is considered to be the main cause of PC. Inflammatory cells are believed to play a crucial role in tumor progression. Therefore, nonsteroidal anti-inflammatory drugs along with their effects on the treatment of inflammation-related diseases, can prevent cancer and its progression by suppressing various inflammatory pathways. Recent evidence shows that nonsteroidal anti-inflammatory drugs are effective in the prevention and treatment of prostate cancer. In this review, we discuss the different pathways through which these drugs exert their potential preventive and therapeutic effects on prostate cancer.

Enhanced Natural Strength: Lamiaceae Essential Oils and Nanotechnology in In Vitro and In Vivo Medical Research.

The Lamiaceae is one of the most important families in the production of essential oils known to have a wide spectrum of biological activity. Recent research has highlighted the dermatological capabilities of various Lamiaceae essential oils, which appear to offer potential in free radical scavenging and anti-inflammatory activity. Some have also been extensively studied for their tissue remodeling and wound-healing, anti-aging, anti-melanogenic, and anti-cancer properties. Certain Lamiaceae essential oils are promising as novel therapeutic alternatives for skin disorders. This potential has seen substantial efforts dedicated to the development of modern formulations based on nanotechnology, enabling the topical application of various Lamiaceae essential oils. This review provides a comprehensive summary of the utilization of various essential oils from the Lamiaceae family over the past decade. It offers an overview of the current state of knowledge concerning the use of these oils as antioxidants, anti-inflammatory agents, wound-healers, anti-aging agents, anti-melanogenic agents, and anticancer agents, both alone and in combination with nanoparticles. Additionally, the review explores their potential applicability in patents regarding skin diseases.

In Vitro Evaluation and In Silico Calculations of the Antioxidant and Anti-Inflammatory Properties of Secondary Metabolites from Leonurus sibiricus L. Root Extracts.

Leonurus sibiricus L. has great ethnobotanical and ethnomedicinal significance. This study aimed to assess the antioxidant and anti-inflammatory properties of Leonurus sibiricus L. transgenic roots extracts transformed by Rhizobium rhizogenes, with and without the AtPAP1 transcriptional factor. The study determined the total phenolic and flavonoid contents, as well as in vitro antioxidant assays, including hydrogen peroxide and nitric oxide scavenging activity. In addition, in silico computational studies and molecular docking were conducted to evaluate the antioxidant and anti-inflammatory potential of the identified compounds. The ligands were docked to NADPH oxidase, cyclooxygenase 2,5-lipoxygenase, inducible nitric synthase and xanthine oxidase: enzymes involved in the inflammatory process. The total phenolic and flavonoid contents ranged from 85.3 ± 0.35 to 57.4 ± 0.15 mg/g GAE/g and 25.6 ± 0.42 to 18.2 ± 0.44 mg/g QUE/g in hairy root extracts with and without AtPAP1, respectively. H2O2 scavenging activity (IC50) was found to be 29.3 µg/mL (with AtPAP1) and 37.5 µg/mL (without AtPAP1 transcriptional factor), and NO scavenging activity (IC50) was 48.0 µg/mL (with AtPAP1) and 68.8 µg/mL (without AtPAP1 transcriptional factor). Leonurus sibiricus L. transformed root extracts, both with and without AtPAP1, are a source of phytochemicals belonging to different classes of molecules, such as flavonoids (catechin and rutin), phenolic compounds (caffeic acid, coumaric acid, chlorogenic acid, ferulic acid) and phenylpropanoid (verbascoside). Among the radicals formed after H removal from the different -OH positions, the lowest bond dissociation enthalpy was observed for rutin (4'-OH). Rutin was found to bind with cyclooxygenase 2, inducible nitric synthases and xanthine oxidase, whereas chlorogenic acid demonstrated optimal binding with 5-lipoxygenase. Therefore, it appears that the Leonurus sibiricus L. transformed root extract, both with and without the AtPAP1 transcriptional factor, may serve as a potential source of active components with antioxidant and anti-inflammatory potential; however, the extract containing AtPAP1 demonstrates superior activities. These properties could be beneficial for human health.

Chitosan Nanoparticles-Preparation, Characterization and Their Combination with Ginkgo biloba Extract in Preliminary In Vitro Studies.

Nanoparticles (NPs), due to their size, have a key position in nanotechnology as a spectrum of solutions in medicine. NPs improve the ability of active substances to penetrate various routes: transdermal, but also digestive (active endocytosis), respiratory and injection. Chitosan, an N-deacetylated derivative of chitin, is a natural biodegradable cationic polymer with antioxidant, anti-inflammatory and antimicrobial properties. Cross-linked chitosan is an excellent matrix for the production of nanoparticles containing active substances, e.g., the Ginkgo biloba extract (GBE). Chitosan nanoparticles with the Ginkgo biloba extract (GBE) were obtained by ion gelation using TPP as a cross-linking agent. The obtained product was characterized in terms of morphology and size based on SEM and Zeta Sizer analyses as well as an effective encapsulation of GBE in nanoparticles-FTIR-ATR and UV-Vis analyses. The kinetics of release of the active substance in water and physiological saline were checked. Biological studies were carried out on normal and cancer cell lines to check the cytotoxic effect of GBE, chitosan nanoparticles and a combination of the chitosan nanoparticles with GBE. The obtained nanoparticles contained and released GBE encapsulated in research media. Pure NPs, GBE and a combination of NPs and the extract showed cytotoxicity against tumor cells, with no cytotoxicity against the physiological cell line.

Food Anthocyanins: Malvidin and Its Glycosides as Promising Antioxidant and Anti-Inflammatory Agents with Potential Health Benefits.

Anthocyanins are flavonoid compounds that are abundantly present in fruits and vegetables. These compounds contribute to the color of these foods and offer various health benefits to consumers due to their biological properties. There are more than 1000 types of anthocyanins in nature, all derived from 27 anthocyanidin aglycones that have different glycosylations and acylations. Malvidin is one of the most well-known anthocyanidins. Several studies, including those conducted on cell lines, animals, and humans, have suggested that malvidin and its glycosides possess anti-carcinogenic, diabetes-control, cardiovascular-disease-prevention, and brain-function-improvement properties. These health benefits are primarily attributed to their antioxidant and anti-inflammatory effects, which are influenced by the molecular mechanisms related to the expression and modulation of critical genes. In this article, we review the available information on the biological activity of malvidin and its glycosides concerning their health-promoting effects.

Creating an Innovative Artificial Intelligence-Based Technology (TCRact) for Designing and Optimizing T Cell Receptors for Use in Cancer Immunotherapies: Protocol for an Observational Trial.

BACKGROUND: Cancer continues to be the leading cause of mortality in high-income countries, necessitating the development of more precise and effective treatment modalities. Immunotherapy, specifically adoptive cell transfer of T cell receptor (TCR)-engineered T cells (TCR-T therapy), has shown promise in engaging the immune system for cancer treatment. One of the biggest challenges in the development of TCR-T therapies is the proper prediction of the pairing between TCRs and peptide-human leukocyte antigen (pHLAs). Modern computational immunology, using artificial intelligence (AI)-based platforms, provides the means to optimize the speed and accuracy of TCR screening and discovery. OBJECTIVE: This study proposes an observational clinical trial protocol to collect patient samples and generate a database of pHLA:TCR sequences to aid the development of an AI-based platform for efficient selection of specific TCRs. METHODS: The multicenter observational study, involving 8 participating hospitals, aims to enroll patients diagnosed with stage II, III, or IV colorectal cancer adenocarcinoma. RESULTS: Patient recruitment has recently been completed, with 100 participants enrolled. Primary tumor tissue and peripheral blood samples have been obtained, and peripheral blood mononuclear cells have been isolated and cryopreserved. Nucleic acid extraction (DNA and RNA) has been performed in 86 cases. Additionally, 57 samples underwent whole exome sequencing to determine the presence of somatic mutations and RNA sequencing for gene expression profiling. CONCLUSIONS: The results of this study may have a significant impact on the treatment of patients with colorectal cancer. The comprehensive database of pHLA:TCR sequences generated through this observational clinical trial will facilitate the development of the AI-based platform for TCR selection. The results obtained thus far demonstrate successful patient recruitment and sample collection, laying the foundation for further analysis and the development of an innovative tool to expedite and enhance TCR selection for precision cancer treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04994093; https://clinicaltrials.gov/ct2/show/NCT04994093. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45872.

New Data on Anti-Inflammatory and Wound Healing Potential of Transgenic Senna obtusifolia Hairy Roots: In Vitro Studies.

Asthma is an inflammatory disease whose etiology remains unclear. Its characteristics encompass a wide range of clinical symptoms, inflammatory processes, and reactions to standard therapies. Plants produce a range of constitutive products and secondary metabolites that may have therapeutic abilities. The aim of this study was to determine the effects of Senna obtusifolia transgenic hairy root extracts on virus-induced airway remodeling conditions. Three cell lines were incubated with extracts from transformed (SOA4) and transgenic (SOPSS2, with overexpression of the gene encoding squalene synthase 1) hairy roots of Senna obtusifolia in cell lines undergoing human rhinovirus-16 (HRV-16) infection. The effects of the extracts on the inflammatory process were determined based on the expression of inflammatory cytokines (IL-8, TNF-α, IL-1α and IFN-γ) and total thiol content. The transgenic Senna obtusifolia root extract reduced virus-induced expression of TNF, IL-8 and IL-1 in WI-38 and NHBE cells. The SOPSS2 extract reduced IL-1 expression only in lung epithelial cells. Both tested extracts significantly increased the concentration of thiol groups in epithelial lung cells. In addition, the SOPPS2 hairy root extract yielded a positive result in the scratch test. SOA4 and SOPPS2 Senna obtusifolia hairy root extracts demonstrated anti-inflammatory effects or wound healing activity. The SOPSS2 extract had stronger biological properties, which may result from a higher content of bioactive secondary metabolites.

PD-1 and PD-L1 Expression Levels as a Potential Biomarker of Chronic Rhinosinusitis and Head and Neck Cancers.

Inflammation is an etiological factor of various chronic diseases contributing to more than 50% of worldwide deaths. In this study, we focus on the immunosuppressive role of the programmed death-1 (PD-1) receptor and its ligand (PD-L1) in inflammatory-related diseases, including chronic rhinosinusitis and head and neck cancers. The study included 304 participants. Of this number, 162 patients had chronic rhinosinusitis with nasal polyps (CRSwNP), 40 patients had head and neck cancer (HNC) and there were 102 healthy subjects. The expression level of the PD-1 and PD-L1 genes in the tissues of the study groups was measured by qPCR and Western blot methods. The associations between the age of the patients and the extent of disease and genes' expression were evaluated. The study showed a significantly higher mRNA expression of PD-1 and PD-L1 in the tissues of both the CRSwNP and HNC patient groups compared to the healthy group. The severity of CRSwNP significantly correlated with the mRNA expression of PD-1 and PD-L1. Similarly, the age of the NHC patients influenced PD-L1 expression. In addition, a significantly higher level of PD-L1 protein was noticed also for both the CRSwNP and HNC patient groups. The increased expression of PD-1 and PD-L1 may be a potential biomarker of inflammatory-related diseases, including chronic rhinosinusitis and head and neck cancers.