Therapeutic Use Research Articles

The importance of targeted next-generation sequencing based genomic profiling at diagnosis of childhood acute myeloid leukemia: a single center experience

Background. The management of pediatric acute myeloid leukemia (AML) is based on the prognostic risk classification of initial leukemia. Targeted next-generation sequencing (NGS) is a reliable method used to identify recurrently mutated genes of pediatric AML and associated prognosis. Methods. In this study, we retrospectively evaluated the prognostic, and therapeutic utility of a targeted NGS panel covering twenty-five genes, in 21 children with de novo and 8 with relapsed or secondary AML. Results. Variants were detected in 44.8% of patients, and 63.2% of them were in the signaling pathway genes. The number of variants per patient and diversity increased with age. The panel results affected hematopoietic stem cell transplantation decisions, especially in core binding factor AML, and allowed the categorization of diseases according to current classifications. Panel results also pointed out predisposition to germline leukemia to the extent of the panel coverage. No targeted therapy was used based on the variants, and none of the variants were used to monitor minimal residual disease. Conclusions. Targeted NGS results, along with well-known genetic aberrations and treatment responses, can guide treatment modalities. The coverage of the routine panels should include proven mutations of childhood AML and germline leukemia predisposition genes.

Striking Cardioprotective Effects of an Adiponectin Receptor Agonist in an Aged Mouse Model of Duchenne Muscular Dystrophy

Adiponectin (ApN) is a hormone with potent effects on various tissues. We previously demonstrated its ability to counteract Duchenne muscular dystrophy (DMD), a severe muscle disorder. However, its therapeutic use is limited. AdipoRon, an orally active ApN mimic, offers a promising alternative. While cardiomyopathy is the primary cause of mortality in DMD, the effects of ApN or AdipoRon on dystrophic hearts have not been investigated. Our recent findings demonstrated the significant protective effects of AdipoRon on dystrophic skeletal muscle. In this study, we investigated whether AdipoRon effects could be extended to dystrophic hearts. As cardiomyopathy develops late in mdx mice (DMD mouse model), 14-month-old mdx mice were orally treated for two months with AdipoRon at a dose of 50 mg/kg/day and then compared with untreated mdx and wild-type (WT) controls. Echocardiography revealed cardiac dysfunction and ventricular hypertrophy in mdx mice, which were fully reversed in AdipoRon-treated mice. AdipoRon also reduced markers of cardiac inflammation, oxidative stress, hypertrophy, and fibrosis while enhancing mitochondrial biogenesis via ApN receptor-1 and CAMKK2/AMPK pathways. Remarkably, treated mice also showed improved skeletal muscle strength and endurance. By offering protection to both cardiac and skeletal muscles, AdipoRon holds potential as a comprehensive therapeutic strategy for better managing DMD.

Series of Novel Integrastatins Analogues: In silico Study of Physicochemical and Bioactivity Parameters

Integrastatins are naturally occurring heterotetracyclic compounds with a broad spectrum of biological activity. A number of new structural analogues of integrastatins 2a-u have been synthesized using a novel one-step method [1], but a systematic theoretical study of their structural features and biological activity has not been realized. This study aimed to in silico investigate physicochemical and bioactivity properties for a series of 21 new synthetic analogues of natural integrastatins. Global chemical reactivity descriptors was assessed using DFT B3LYP 6-311++G(d, p) CPCM (solvent — water) calculations. High ionization potential IP in the range from 5.9 to 7.1 eV and electron affinity EA at the level of 2.1 to 3.2 eV were shown, which together with a sufficiently large energy gap DEgap from 3.8 to 4.6 eV indicates the hard nature of the compounds 2a-u. Antiviral activity and inhibitory potential as CYP2C19 inducers were identified using the PASSOnline resource. According to the results of molecular docking studies Human immunodeficiency virus HIV-1 reverse transcriptase protein (PDB ID: 3V81) and protein of the RNA-dependent RNA polymerase of the SARS-CoV-2 (PDB ID: 7AAP) can serve as a likely biological target for the compounds 2a-u. Potentially high oral efficacy and a promising safety profile for the therapeutic use were showed using ADMETlab 3.0 online portal. Further experimental in vitro and in vivo studies of the pharmaceutical potential of compounds 2a-u is need for more accurate evaluation the assumptions made on the basis of in silico approach.

The IPEDs assemblage: Tracing the entanglements of biomedicine, technology, enhancement and anti-doping policies in sport and society.

The US Anti-Doping Agency (USADA) and Ultimate Fighting Championship (UFC) recently ended their anti-doping partnership amidst controversy. We treat this decision, and the motivations underpinning it, as a means of exploring the complexities of anti-doping norms and the blurred lines between image and performance enhancing drug (IPED) use in sport and wider society. Drawing ideas from assemblage thinking, we analyse the evolving power dynamics surrounding IPED use, anti-doping policy, and the role of popular athletes in shaping societal perceptions of the use of, and potential harms associated with IPEDs. The study offers a case analysis of recent controversies in the UFC to investigate the entanglements of biomedicine, technology and celebrity culture in what we call the IPED assemblage. The 2023 termination of the USADA-UFC partnership has sparked debates about shifts in anti-doping standards, raising concerns about weaker testing protocols and perceptions of IPED normalisation. The case of Conor McGregor's injury recovery and alleged IPED use underscores the blurred lines between therapeutic and enhancement drug use within the IPED assemblage, challenging conventional distinctions between 'good' and 'bad' drugs in the context of sports management and anti-doping policy making. We highlight the inadequacy of current doping policies in responding to the IPED assemblage and highlight the need to shift public discourse to foster a more critical understanding of therapeutic and enhancement strategies to drive innovation in anti-doping frameworks.

Can a diet rich in Brassicaceae help control Helicobacter pylori infection? A systematic review

IntroductionHelicobacter pylori (Hp) infection is highly prevalent globally and poses a significant public health challenge due to its link with chronic gastritis, peptic ulcers, and gastric malignancies. Hp’s persistence within the gastric environment, particularly in case of infection with virulent strains, triggers chronic inflammatory responses and mucosal damage. Antibiotic therapy is the primary approach for Hp eradication, but antibiotic resistance and adverse effects hinder treatment efficacy. Emerging evidence suggests that Brassicaceae-derived metabolites could serve as adjunctive therapy for Hp infection, offering potential antimicrobial and anti-inflammatory benefits.MethodsA systematic literature review was conducted following PRISMA guidelines to assess the impact of Brassicaceae-rich diets on Hp infection control. Searches were performed in MEDLINE PubMed, Web of Science, and the Cochrane Library until 18 October 2023, without language or date restrictions. Eligible studies meeting PICOS criteria were included, encompassing populations infected with Hp or Hp-infected human cell cultures, interventions involving Brassicaceae consumption or its bioactive molecules, and outcomes related to Hp infection control, antibiotic therapy interactions, reduction of antibiotic side effects, and inflammation mitigation. Animal studies, cell line experiments, reviews unrelated to the research objectives, and studies on Hp-related gastric cancer were excluded.ResultsAvailable evidence indicates that Brassicaceae consumption exhibits the potential to reduce Hp colonization but achieving complete eradication of the pathogen remains challenging. Conflicting results regarding the efficacy of broccoli in Hp treatment emerge, with certain investigations suggesting limited effectiveness. Other studies point to a potential for heightened eradication rates when combined with standard triple therapy. Furthermore, promising outcomes are observed with broccoli extract supplements, indicating their role in mitigating Hp-induced gastric mucosal damage. In fact, it is noteworthy that sulforaphane and its derivatives manifest notable reductions in pro-inflammatory markers, indicative of their anti-inflammatory properties. Adverse events associated with antibiotic therapy seem unaffected by sulforaphane derivatives or probiotics. However, individual responses to these treatments vary, underscoring the unpredictability of their efficacy in ameliorating antibiotic therapy-related side effects.ConclusionOur systematic review highlights the potential of Brassicaceae-rich diets as adjunctive therapy for Hp infection, offering synergistic interactions with antibiotics and possibly mitigating antibiotic side effects and inflammation. Further research, particularly well-designed randomized trials, is warranted to elucidate the therapeutic efficacy and optimal utilization of Brassicaceae-derived metabolites in managing human Hp-related diseases.

Development of Hydrogel Delivery Systems for Anti-Inflammatory Action

Hydrogels' biocompatibility, adjustable characteristics, and capacity for controlled drug release have made them attractive delivery systems for anti-inflammatory drugs. These technologies lessen the drawbacks of traditional medication delivery techniques, namely their low bioavailability and systemic side effects. The development, workings, and developments of hydrogel-based delivery methods specifically designed to reduce inflammation are examined in this paper. It explores the various kinds of hydrogels, their potential for therapeutic use, and the present difficulties in bringing these systems from the lab to the clinic.

The Relevance of the Concept of Psychic Energy in Contemporary Psychology

The article focuses on the historical development and contemporary research in the fields of bioelectrical processes and psychic energy, emphasizing their significance in medicine and psychology. Special attention is given to Luigi Galvani’s contribution, who discovered bioelectrical activity through experiments on animals, leading to the concept of galvanization — the therapeutic use of electricity. The article also examines ideas of psychic energy introduced by Sigmund Freud, who defined libido as a form of psychic energy, and Carl Jung, who expanded the concept to include spiritual aspects. Additionally, modern approaches such as Mihaly Csikszentmihalyi’s theory of "flow" are discussed, exploring the relationship between psychic energy and states of productivity and well-being. The author emphasizes the need for interdisciplinary collaboration in further research on these topics and the importance of standardizing terminology to ensure the scientific and clinical applicability of the concept of psychic energy in contemporary studies and practice.

A narrative review of thalassotherapy and the health benefits of seawater and coastal climates.

Thalassotherapy refers to the therapeutic use of controlled exposure to marine environments and their natural elements for health promotion. This review aims to summarize evidence-based clinical applications of thalassotherapy. A narrative review was conducted, with PubMed searched in September 2024 for clinical studies evaluating the efficacy of thalassotherapy. Relevant evidence was summarized and critically analyzed. A total of 566 articles were identified, of which 16 studies met the inclusion criteria. Thalassotherapy was primarily studied for its effects on skin disorders, including psoriasis, atopic dermatitis, and vitiligo, as well as rheumatic conditions like fibromyalgia and ankylosing spondylitis. The intervention showed significant improvements in disease severity and patient quality of life, with the strongest evidence seen in psoriasis and fibromyalgia treatment. Thalassotherapy appears beneficial for symptom relief in several conditions, particularly skin and rheumatic disorders. However, further research is needed to quantify its effect size, evaluate long-term benefits, assess potential risks, and identify factors that may influence treatment outcomes.

Longitudinal assessment of DNA recovery from post-mortem whole blood stored in EDTA, sodium fluoride/potassium oxalate and additive-free tubes.

Adverse drug reactions and fatalities can result from therapeutic drug use due to genetic deficiencies in drug-metabolizing enzymes. In cases where ancillary testing may not reveal a clear cause of death, molecular autopsies can be valuable. However, forensic mortuaries do not retain DNA samples in all cases, which hinders subsequent genetic testing if it is later deemed necessary. This study aimed to evaluate whether post-mortem whole blood samples collected for toxicological analysis, could provide viable DNA for genetic testing after varying storage periods. Thirty deceased individuals were recruited with informed consent. Blood collected at autopsy from each individual was stored in two sodium fluoride/potassium oxalate (gray-top) tubes, two additive-free (red-top) tubes and one ethylenediaminetetraacetic acid (EDTA; purple-top) tube- the latter recommended for DNA analysis. Blood from one gray-top and one red-top tube were sampled for toxicological analysis prior to DNA analysis, while the remaining samples (acting as controls) underwent DNA analysis immediately. DNA analysis involved DNA extraction and DNA concentration and degradation assessment. Blood samples were stored at 4°C and DNA extraction and analysis was repeated one year and then five years later. Toxicological sampling did not significantly influence DNA results. DNA concentration and quality significantly decreased over time for all sample types, with DNA from red-top tubes showing the greatest decline. The study showed that DNA testing for drug-metabolizing enzymes was feasible on whole blood that had been stored for five years. This finding supports the potential for retrospective genetic testing in cases of adverse drug reactions and fatalities.

A Comprehensive Study on the Renal Protective Effects of Polyherbal Extract Formulation and Their Impact on Kidney Function in Rats

Background: The nephroprotective effects of herbal extracts have increasingly gained attention due to the rise in kidney diseases and the limitations of conventional treatments. This study explores the renal protective properties of a polyherbal extract formulation composed of Ziziphus spina-christi, Trigonella foenum-graecum and Nigella sativa (ZTN) in Wistar albino rats. Methods: Three groups of adult male and female Wistar albino rats consisting of the control group that received only water, another group was administered with 100 mg/kg of the polyherbal (ZTN herbal) formulation, while the last group was administered with 250 mg/kg of the ZTN polyherbal extract formulation. The treatments administered for 14 days and thereafter Kidney weight, uric acid, Blood Urea Nitrogen (BUN) and creatinine levels were assessed to assess renal function. Histological analysis was conducted for tissue integrity evaluation. Result: The polyherbal extract formulation of ZTN induced a dose-dependent increase in kidney weight in both male and female rats. Uric acid levels decreased significantly in a dose-dependent manner, with the most substantial reduction at 250 mg/kg. BUN levels also showed a notable decrease, particularly at the higher dose, indicating enhanced renal function. Creatinine levels exhibited a significant dose-dependent reduction, with female rats showing higher baseline levels but greater overall reductions. Histological analysis revealed mild histological changes at 100 mg/mL and severe changes at 250 mg/mL. Histological changes include glomerular hypertrophy and tubular necrosis, more pronounced at higher doses. The polyherbal extract formulation of ZTN demonstrated significant nephroprotective effects, reducing uric acid, BUN and creatinine levels in a dose-dependent manner. Interestingly, an observation of gender-based differences occur in female rats showing higher baseline levels but greater reductions with treatment. These findings support the potential therapeutic use of polyherbal extracts in managing renal health, emphasizing the importance of dose regulation to avoid adverse effects.

Development and validation of a clinical prediction model for blastocyst formation during IVF/ICSI-ET

PurposeThis study aims to create and validate a clinical model that predict the probability of blastocyst formation in IVF/ICSI-ET cycles.MethodsThis study employed a retrospective methodology, gathering data from 4961 cleavage-stage embryos that cultured in the reproductive center’s of the Fourth Hospital of Hebei Medical University between June 2020 and March 2024. 3472 were in the training set and 1489 were in the validation set when it was randomly split into the training set and validation set in a 7:3 ratio. The study employed both univariate and multivariate logistic regression analysis to determine the factors those influence in the process of blastocyst formation. Based on the multiple regression model, a predictive model of blastocyst formation during IVF was created. The calibration and decision curves were used to assess the effectiveness and therapeutic usefulness of this model.ResultsThe following factors independently predicted the probability of blastocyst formation: the method of insemination, number of oocytes retrieved, pronuclear morphological score, the number of cleavage ball, cleavage embryo symmetry, fragmentation rate and morphological score and basal P levels of female. The receiver operating characteristic curve’s area under the curve (AUC) in the training set is 0.742 (95% CI: 0.724,0.759), while the validation set’s AUC is 0.729 (95% CI: 0.703,0.755), indicating a rather high clinical prediction capacity.ConclusionOur generated nomogram has the ability to forecast the probability of blastocyst formation in IVF, hence can assist clinical staff in making informed decisions.

Novel Schiff Base Sulfonate Derivatives as Carbonic Anhydrase and Acetylcholinesterase Inhibitors: Synthesis, Biological Activity, and Molecular Docking Insights.

Sulfonate derivatives are an essential class of compounds with diverse pharmacological applications. This study presents the synthesis and detailed characterization of six novel Schiff base sulfonate derivatives (L1-L6) through spectroscopic techniques (FTIR and NMR). Their inhibitory potential was evaluated against human carbonic anhydrase isoenzymes (hCA I and hCA II) and acetylcholinesterase (AChE), which are crucial therapeutic targets for diseases such as glaucoma, epilepsy, and Alzheimer's disease. The Kivalues for the compounds concerning AChE, hCA I, and hCA II enzymes were in the ranges of, 106.10 ± 14.73-422.80 ± 17.64 nM (THA: 159.61± 8.41 nM), 116.90 ± 24.40-268.00 ± 35.84 nM (AAZ: 439.17 ± 9.30 nM), and 177.00 ± 35.03-435.20 ± 75.98 nM (AAZ: 98.28 ± 1.69 nM), respectively. Molecular docking analyses revealed key interactions within the active sites of the enzymes, including hydrogen bonding with critical residues and π-π stacking interactions. Notably,L3demonstrated superior inhibition against hCA I (Ki: 116.90 ± 24.40 nM) and AChE (Ki: 106.10 ± 14.73 nM), positioning it as a promising lead compound. This comprehensive investigation contributes to the development of isoform-specific inhibitors for therapeutic use and provides valuable insights into their binding mechanisms.

Chronic inorganic nitrate supplementation does not improve metabolic health and worsens disease progression in mice with diet-induced obesity.

Inorganic nitrate (NO3-) has been proposed to be of therapeutic use as a dietary supplement in obesity and related conditions including the Metabolic Syndrome (MetS), type-II diabetes and metabolic dysfunction associated steatotic liver disease (MASLD). Administration of NO3- to endothelial nitric oxide synthase-deficient mice reversed aspects of MetS, however the impact of NO3- supplementation in diet-induced obesity is not well understood. Here we investigated the whole-body metabolic phenotype and cardiac and hepatic metabolism in mice fed a high-fat high-sucrose (HFHS) diet for up to 12-months of age, supplemented with 1 mM NaNO3 (or NaCl) in their drinking water. HFHS-feeding was associated with a progressive obesogenic and diabetogenic phenotype, which was not ameliorated by NO3-. Furthermore, HFHS-fed mice supplemented with NO3- showed elevated levels of cardiac fibrosis, and accelerated progression of MASLD including development of hepatocellular carcinoma in comparison with NaCl-supplemented mice. NO3- did not enhance mitochondrial b-oxidation capacity in any tissue assayed and did not suppress hepatic lipid accumulation, suggesting it does not prevent lipotoxicity. We conclude that NO3- is ineffective in preventing the metabolic consequences of an obesogenic diet and may instead be detrimental to metabolic health against the background of HFHS-feeding. This is the first report of an unfavorable effect of long-term nitrate supplementation in the context of the metabolic challenges of overfeeding, warranting urgent further investigation into the mechanism of this interaction.

Assembly of Recombinant Proteins into β-Sheet Fibrillating Peptide-Driven Supramolecular Hydrogels for Enhanced Diabetic Wound Healing.

Supramolecular hydrogels offer a noncovalent binding platform that preserves the bioactivity of structural molecules while enhancing their stability, particularly in the context of diabetic wound repair. In this study, we developed protein-peptide-based supramolecular hydrogels by assembling β-sheet fibrillizing peptides (designated Q11) with β-tail fused recombinant proteins. The Q11 peptides have the ability to drive the gradated assembly of N- or C-terminal β-sheet structure (β-tail) fused recombinant proteins. We first investigated the assembly properties of Q11 and assessed its stability under varying pH and temperature conditions by combining Q11 with two β-tail fused fluorescent proteins. The results showed that Q11 enhanced the tolerance of the fluorescent proteins to changes in pH and temperature. Building upon these findings, we designed collagen-like proteins and Sonic Hedgehog-fused recombinant proteins (CLP-Shh) that could be assembled with Q11 to form peptide-protein supramolecular hydrogels. These hydrogels demonstrated the ability to improve cell viability and migration and upregulate key markers of cell growth. Further in vivo studies revealed that the Q11-driven supramolecular hydrogel effectively enhances diabetic wound healing and epidermal regeneration by promoting the expression of epidermal-related proteins and immune factors. This study highlights the potential of supramolecular hydrogels for clinical applications and their promise in the development of biofunctional hydrogels for therapeutic use.

Pharmaceutical and therapeutic utility of Hingula

Rasashastra is a branch of Ayurveda which deals with the various pharmaceutical processes viz. Shodhana, Marana, etc. and gives detailed description regarding the Metals, Minerals, Poisonous herbal drugs and Animal products commonly used as therapeutically in practice of Ayurveda. Hingula, a significant component in Rasashastra, is categorized as a Sadharana Rasa, meaning a common yet potent substance used in various Ayurvedic formulations. Known in the modern context as cinnabar, Hingula primarily contains mercury sulfide and has been utilized for centuries in the many preparations. Its importance in Rasashastra lies in its ability to enhance the potency and efficacy of formulations, particularly those aimed at rejuvenation, longevity, and the treatment of complex diseases. The careful detoxification and processing of Hingula is crucial, as it is a potent substance that can be toxic if not properly handled. This paper explores the traditional methods of Hingula purification, its pharmacological properties, and its role in the preparation of various Ayurvedic medicines.

A Comprehensive Review on the Chinese Herbal Medicine Quzhiqiao

Quzhiqiao is a Chinese herbal medicine widely used in Zhejiang Province of China, which originates from the cultivar Citrus aurantiun ‘Changshanhuyou’, named Changshanhuyou in Chinese. Citrus aurantiun ‘Changshanhuyou’ is a botanical variety of C. aurantium L., which is obtained after long-term domestication. It belongs to the Rutaceae family and mainly grows in Changshan County, Zhejiang Province, China. Quzhiqiao is an authentic Chinese medicinal material in the Zhejiang area with various pharmacological and curative effects. A comprehensive review and indepth analysis of scientific literature on Quzhiqiao was conducted, utilizing diverse electronic databases and additional sources. This review provides a comprehensive overview of its chemical components, standardized quality control, pharmacological activity, and mechanism of action, which also outlines future perspectives, highlighting the necessity for further research for harnessing the potential of the therapeutic use of Quzhiqiao.

Pharmacokinetic Prediction of Immediate- and Extended-Release Tablets for Patients with Liver Disease Using Whole Body Physiologically-Based Pharmacokinetic Modeling for the Antipsychotic Drug Quetiapine.

Although quetiapine metabolism occurs extensively in the liver and careful dosing is recommended in patients with liver disease, there has been a paucity of pharmacometric studies to adjust the clinical dose of quetiapine according to liver-disease severity. This study aimed to establish a whole-body, physiologically-based pharmacokinetic (WB-PBPK) model to explain interindividual variability in quetiapine PK and quantitatively predict PK in patients with liver disease. The developed WB-PBPK model well described the PK characteristics of different quetiapine regimens in healthy populations. The PK predictions could also be applied to patients with schizophrenia (without significant differences from healthy subjects). For the same total dose of quetiapine, both immediate-release (IR) and extended-release (ER) tablets showed significantly increased exposure and decreased clearance in patients with liver disease compared to healthy subjects. The model showed that steady-state plasma quetiapine concentrations exceeded the usual therapeutic range after multiple doses of IR tablets 250mg three times daily or ER tablets 800mg once daily in patients with liver disease. Therefore, the doses of quetiapine IR or ER tablets could be reduced by 0.10-0.50 times depending on liver-disease severity, so that mean steady-state plasma concentrations could be positioned near the therapeutic range. WB-PBPK modeling for quetiapine enabled quantitative prediction of PK according to IR or ER formulation and liver-disease severity. The results of this study provide useful data for improving the therapeutic use of quetiapine by enabling dose selection based on formulation and liver-disease severity.

MiR-198 targets TOPORS: implications for oral squamous cell carcinoma pathogenesis.

miRNAs play a critical role in the progression of various diseases, including oral squamous cell carcinoma (OSCC), which represents a major health concern and is one of the leading causes for new cancer cases worldwide. The miRNA dysregulation causes havoc and could be attributed to various factors, with epigenetic silencing of tumor suppressor genes being a major contributor to tumorigenesis. In this study, we have explored the tumor suppressive role of miR-198 in OSCC. The tumor suppressive effect of miR-198 is established using miRNA analysis in OSCC cell lines, patient samples and xenograft nude mice model. The relationship between the miR-198 and TOPORS is explored using bioinformatics analyses, qRT-PCR, dual-luciferase reporter assay, Western blotting and cancer hall marks assays. The hypermethylation of the MIR198 promoter is confirmed using bisulfite sequencing PCR. We have found miR-198 to be upregulated in OSCC cells treated with 5-Azacytidine, a known DNA methyltransferase inhibitor. Upregulation of miR-198 in 5-Azacytidine treated OSCC cells appears to be due to methylation of the MIR198 promoter. Using bioinformatics analysis and dual-luciferase reporter assay, we have identified TOPORS (TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase) as a novel gene target for miR-198. miR-198-mediated repression of TOPORS decreases cell proliferation and anchorage-independent growth and enhances apoptosis of OSCC cells, which is dependent on the presence of the 3'UTR in TOPORS. An inverse correlation between the expression levels of miR-198 and TOPORS is observed in OSCC patient samples, highlighting the biological relevance of their interaction. Delivery of a synthetic miR-198 mimic to OSCC cells results in a significant decrease in xenograft size in nude mice, potentiating its use in therapeutics. These results suggest that miR-198 is epigenetically silenced in OSCC, which promotes tumor growth, in part, by upregulating the levels of TOPORS.

Evidence for therapeutic use of cannabidiol for nail-patella syndrome-induced pain in a real-world pilot study

Nail-patella syndrome (NPS) is a rare genetic disease characterized by dysplastic nails, patella abnormalities, skeletal malformation, and chronic pain. Although chronic pain in NPS is mainly due to bone and musculoskeletal symptoms, it can also result from neurological dysfunction. Conventional analgesics are often insufficient to relieve NPS-associated chronic pain. Cannabinoids, which act on the serotonergic and/or noradrenergic pain systems, may therefore represent valuable non-psychoactive alternatives for managing pain in these patients. The effectiveness and safety of synthetic cannabidiol (CBD) for the management of NPS-associated pain was assessed using real-world data from a pilot cohort of patients with NPS who received a 3-month treatment with oral CBD. The treatment (median dose of 900 mg/day) was associated with a significant reduction in pain intensity (mean score of 7.04 ± 0.24 at initiation versus 4.04 ± 0.38 at 3 months, N = 28, p < 0.0001), which correlated with changes in the peripheral concentration of noradrenaline (r = 0.705, 95% CI [0.44–0.86], p < 0.0001). Health-related quality of life and other NPS-associated symptoms also improved in most patients. CBD treatment was well tolerated and no elevations in liver enzyme levels were reported. Synthetic CBD therefore appears to be a safe and effective treatment option for managing NPS-associated chronic pain.

Immunomodulation via the Endocannabinoid System: Mechanisms and Therapeutic Potentials

The endocannabinoid system (ECS) plays a crucial role in regulating immune responses, influencing both innate and adaptive immunity through its interaction with cannabinoid receptors, particularly CB2, which is predominantly expressed on immune cells. This review explores the mechanisms of ECS-mediated immunomodulation, focusing on its ability to balance pro-inflammatory and anti-inflammatory processes, thereby contributing to immune homeostasis. Endocannabinoids, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), modulate immune cell activity, cytokine production, and migration. These actions make the ECS a promising therapeutic target for chronic inflammatory and autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Additionally, the ECS has potential applications in cancer immunotherapy by modulating the tumor microenvironment and enhancing anti-tumor immune responses. Non-psychoactive cannabinoids like cannabidiol (CBD) have emerged as attractive candidates for therapeutic use, offering anti-inflammatory benefits without the adverse psychoactive effects associated with tetrahydrocannabinol (THC). However, challenges remain in understanding the ECS’s complex interactions within the immune system and optimizing cannabinoid-based therapies for clinical use. As research progresses, the ECS may provide novel therapeutic avenues for immune regulation and disease management, contributing to improved outcomes in a variety of immune-related disorders. Keywords: Endocannabinoid system, Immunomodulation, CB2 receptors, Inflammation, Autoimmune diseases