Reliability of magnetic resonance for temporomandibular joint disc perforation: A 12 years retrospective study.

The aim of this study was to evaluate the reliability of magnetic resonance imaging (MRI) in detecting disc perforations in the temporomandibular joint (TMJ), and to establish diagnostic criteria for this purpose. The retrospective analysis included patients who had undergone preoperative MRI and TMJ arthroscopy at the same hospital. Direct and indirect signs of disc abnormalities on MRI were compared with arthroscopic findings of disc perforation. Out of 355 joints evaluated in 185 patients, arthroscopy confirmed disc perforations in 14.7% of cases. Several MRI findings were significantly associated with disc perforation, including anterior disc displacement without reduction (ADDwoR), signal alterations in the mid-disc area, disc deformity (SAMD), retrocondylar disc fragments, osteophytes, condylar bone marrow degeneration (CBMD), and joint effusion in both joint spaces (ESJS-EIJS). Regression analysis revealed that SAMD, osteophytes, and CBDM were strongly associated with disc perforation. The ROC curve showed that MRI had an AUC = 0.791, with a sensitivity of 88.5% and a specificity of 61.5%. Two diagnostic methods, one based on three findings (osteophytes, ADDwoR, and SAMD) and one based on two direct signs (ADDwoR and SAMD), yielded high sensitivity and specificity values of 80.4% and 69.8%, and 84.3% and 62.5%, respectively. In conclusion, MRI demonstrated acceptable accuracy in the detection of TMJ disc perforations, with specific diagnostic criteria offering high sensitivity and specificity. Significant MRI indicators of disc perforation included SAMD, osteophytes, and CBDM. This study provides valuable information on the use of MRI as a diagnostic tool for TMJ disc perforations.

Capecitabine-Related Thrombotic Microangiopathy.

PURPOSE: Renal injury is common in cancer patients and its etiology is multifactorial. Different patterns of renal histological lesions have been described in relation to oncologic treatments, notably acute tubular necrosis and tubulointerstitial nephritis, but also thrombotic microangiopathy (TMA). METHODS: We report a case of TMA secondary to capecitabine in an 82-year-old woman diagnosed with localized colon adenocarcinoma. RESULTS: The patient, with previous normal kidney function, presented with renal impairment during the fourth cycle of chemotherapy. After potential nephrotoxic factors were ruled out, capecitabine was discontinued and a kidney biopsy was performed, which displayed TMA lesions. An improvement in renal function was observed after definitive cessation of cytotoxic chemotherapy. Although rare, renal toxicity in the form of TMA may be associated with the use of cytotoxic agents such as gemcitabine, but there is no reported evidence of its association to capecitabine. Early withdrawal of the drug and nephrology consultation is necessary to prevent irreversible damage. CONCLUSION: We describe, to our knowledge, the first case reported in the literature regarding the possible association of TMA and capecitabine.

Metabolic control analysis of the transsulfuration pathway and the compensatory role of the cysteine transport in Trypanosoma cruzi.

Trypanosoma cruzi is the causal agent of American Trypanosomiasis or Chagas Disease in humans. The current drugs for its treatment benznidazole and nifurtimox have inconveniences of toxicity and efficacy; therefore, the search for new therapies continues. Validation through genetic strategies of new drug targets against the parasite metabolism have identified numerous essential genes. Target validation can be further narrowed by applying Metabolic Control Analysis (MCA) to determine the flux control coefficients of the pathway enzymes. That coefficient is a quantitative value that represents the degree in which an enzyme/transporter determines the flux of a metabolic pathway; those with the highest coefficients can be promising drug targets. Previous studies have demonstrated that cysteine (Cys) is a key precursor for the synthesis of trypanothione, the main antioxidant metabolite in the parasite. In this research, MCA was applied in an ex vivo system to the enzymes of the reverse transsulfuration pathway (RTP) for Cys synthesis composed by cystathionine beta synthase (CBS) and cystathionine gamma lyase (CGL). The results indicated that CGL has 90% of the control of the pathway flux. Inhibition of CGL with propargylglycine (PAG) decreased the levels of Cys and trypanothione and depleted those of glutathione in epimastigotes (proliferative stage in the insect vector); these metabolite changes were prevented by supplementing with Cys, suggesting a compensatory role of the Cys transport (CysT). Indeed, Cys supplementation (but not PAG treatment) increased the activity of the CysT in epimastigotes whereas in trypomastigotes (infective stage in mammals) CysT was increased when they were incubated with PAG. Our results suggested that CGL could be a potential drug target given its high control on the RTP flux and its effects on the parasite antioxidant defense. However, the redundant Cys supply pathways in the parasite may require inhibition of the CysT as well. Our findings also suggest differential responses of the Cys supply pathways in different parasite stages.

Validation and optimization of AFP-based biomarker panels for early HCC detection in Latin America and Europe.

BACKGROUND: HCC is a major cause of cancer death worldwide. Serum biomarkers such as alpha-fetoprotein (AFP), protein induced by vitamin K absence-II, and the Gender, Age, AFP-L3, AFP, Des-gamma-carboxy prothrombin (GALAD) score have been recommended for HCC surveillance. However, inconsistent recommendations in international guidelines limit their clinical utility. METHODS: In this multicenter study, over 2000 patient samples were collected in 6 Latin American and 2 European countries. The performance of the GALAD score was validated in cirrhotic cases, and optimized versions were tested for early-stage HCC and prediagnostic HCC detection. RESULTS: The GALAD score could distinguish between HCC and cirrhosis in Latin American patients with an AUC of 0.76, sensitivity of 70%, and specificity of 83% at the conventional cutoff value of -0.63. In a European cohort, GALAD had an AUC of 0.69, sensitivity of 66%, and specificity of 72%. Optimizing the score in the 2 large multicenter cohorts revealed that AFP-L3 contributed minimally to early-stage HCC detection. Thus, we developed a modified GALAD score without AFP-L3, the ASAP (age, sex, AFP, and protein induced by vitamin K absence-II), which showed promise for early-stage HCC detection upon validation. The ASAP score also identified patients with cirrhosis at high risk for advanced-stage HCC up to 15 months before diagnosis (p < 0.0001) and differentiated HCC from hemangiomas, with a specificity of 100% at 71% sensitivity. CONCLUSION: Our comprehensive analysis of large sample cohorts validates the GALAD score's utility in Latin American, Spanish, and Dutch patients for early-stage HCC detection. The optimized GALAD without AFP-L3, the ASAP score, is a good alternative and shows greater promise for HCC prediction.

S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats.

Hepatic ischemia/reperfusion injury (IRI) can seriously impair liver function. It is initiated by oxidative stress, resulting in inflammation and apoptosis-induced cellular damage. Glutathione (GSH) prevents oxidative stress. S-Adenosylmethionine (SAMet) is a GSH synthesis precursor that avoids the deficit in SAMet-synthetase activity and contributes to intracellular ATP repletion. It also acts as a methyl group donor, stabilizing hepatocyte membranes, among other functions. This study investigated the effect of SAMet on bacterial translocation and levels of proinflammatory cytokines, oxidative stress and apoptosis markers in male Wistar rats subjected to hepatic IRI. Animals were randomly divided into six groups: (1) sham operation, (3) animals undergoing 60 min of ischemia of the right lateral lobe for temporary occlusion of the portal vein and hepatic artery plus 10 min of reperfusion, and (5) the same as (3) but with a reperfusion period of 120 min. Groups 2, 4 and 6, respectively, are the same as (1), (3) and (5), except that animals received SAMet (20 mg/kg) 15 min before ischemia. GSH, ATP, lipid peroxidation (LPO), TNF-α, IL-1ß, IL-6, total caspase-1 and caspase-9, total and cleaved caspase-3, and phosphatidylcholine were determined in the liver. Endotoxin, TNF-α, IL-1ß, IL-6, IL-10 and LPO in vena cava and portal vein blood samples were also measured. Endotoxin and LPO levels as well as proinflammatory cytokines and apoptotic markers increased significantly in animals undergoing IRI, both after 10 and 120 min of reperfusion. IRI produced a significant decrease in GSH, ATP, portal IL-10 and phosphatidylcholine. SAMet treatment prevented these effects significantly and increased survival rate. The study suggests that SAMet exerts protective effects in hepatic IRI.

The unfolded protein response transcription factor XBP1s ameliorates Alzheimer's disease by improving synaptic function and proteostasis.

Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main adaptive pathway to cope with protein folding stress at the ER. Inositol-requiring enzyme-1 (IRE1) operates as a central ER stress sensor, enabling the establishment of adaptive and repair programs through the control of the expression of the transcription factor X-box binding protein 1 (XBP1). To artificially enforce the adaptive capacity of the UPR in the AD brain, we developed strategies to express the active form of XBP1 in the brain. Overexpression of XBP1 in the nervous system using transgenic mice reduced the load of amyloid deposits and preserved synaptic and cognitive function. Moreover, local delivery of XBP1 into the hippocampus of an 5xFAD mice using adeno-associated vectors improved different AD features. XBP1 expression corrected a large proportion of the proteomic alterations observed in the AD model, restoring the levels of several synaptic proteins and factors involved in actin cytoskeleton regulation and axonal growth. Our results illustrate the therapeutic potential of targeting UPR-dependent gene expression programs as a strategy to ameliorate AD features and sustain synaptic function.

Design and biopharmaceutical preclinical characterisation of a new thermosensitive hydrogel for the removal of gastric polyps.

BACKGROUND AND AIMS: Submucosal injection agents are widely used solutions in gastric polyp resection techniques. Currently, many different solutions are used in clinical practice, but most are not authorised for this use or are not biopharmaceutical characterised. The objective of this multidisciplinary work is to test the efficacy of a novel thermosensitive hydrogel designed specifically for this indication. METHODS: A mixture design of various components (Pluronic®, hyaluronic acid and sodium alginate) was carried out to select the combination with optimal properties for this use. Three final thermosensitive hydrogels were selected on which biopharmaceutical characterisation was performed and stability and biocompatibility were analysed. Efficacy in maintaining elevation was tested ex vivo on pig mucosa and in vivo in pigs RESULTS: The mixture design allowed selection of the ideal combinations of agents for the characteristics sought. The thermosensitive hydrogels studied showed high values of hardness and viscosity at 37 °C, maintaining good syringeability. One of them demonstrated superiority in maintaining polyp elevation in the ex vivo assay and non-inferiority in the in vivo assay. CONCLUSION: The thermosensitive hydrogel specifically designed for this use is promising both for its biopharmaceutical characteristics and for its demonstrated efficacy. This study lays the foundation for evaluating the hydrogel in humans.

Guía de práctica clínica para el tratamiento de la rinosinusitis crónica: versión completa / Clinical practice guideline for the treatment of chronic rhinosinusitis: full version

La rinosinusitis (RS) se define como la inflamación de la nariz y los senos paranasales con dos o más síntomas como bloqueo/obstrucción/congestión o secreción nasal (goteo nasal anterior/posterior) más dolor/presión facial y/o reducción o pérdida del sentido del olfato. Adicional, se tienen en cuenta los hallazgos objetivos como la presencia de pólipos nasales y/o descarga mucopurulenta en meato medio y/o edema u obstrucción de la mucosa en el meato medio en la endoscopia nasal. Se pueden considerar o no, los cambios tomográficos como cambios mucosos en el complejo osteomeatal y la mucosa de los senos paranasales. Se reconoce que los síntomas tienen alta sensibilidad, pero baja especificidad, de ahí la necesidad de hallazgos objetivos.

Rhinosinusitis (RS) is defined as inflammation of the nose and sinuses with two or more symptoms such as blockage/obstruction/congestion or nasal discharge. with two or more symptoms such as nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior runny nose) plus facial pain/pressure and/or reduction or loss of the sense of smell. sense of smell. In addition, objective findings such as the presence of nasal polyps and/or nasal presence of nasal polyps and/or mucopurulent discharge from the middle meatus and/or edema or mucosal obstruction or mucosal obstruction in the middle meatus on nasal endoscopy. Tomographic changes may or may not tomographic changes may or may not be considered as mucosal changes in the osteomeatal complex and mucosal osteomeatal complex and the mucosa of the paranasal sinuses. It is recognized that the symptoms symptoms have high sensitivity but low specificity, hence the need for objective findings. findings.

Guía de práctica clínica para el tratamiento de la rinosinusitis crónica: versión corta para profesionales de la salud. Colombia-2023 / Clinical practice guideline for the management of chronic rhinosinusitis: short version for health care professionals. Colombia-2023

La rinosinusitis (RS) se define como la inflamación de la nariz y los senos paranasales con dos o más síntomas como bloqueo/obstrucción/congestión o secreción nasal (goteo nasal anterior/posterior) más dolor/presión facial y/o reducción o pérdida del sentido del olfato. Adicional, se tienen en cuenta los hallazgos objetivos como la presencia de pólipos nasales y/o descarga mucopurulenta en meato medio y/o edema u obstrucción de la mucosa en el meato medio en la endoscopia nasal.

Rhinosinusitis (RS) is defined as inflammation of the nose and sinuses with two or more symptoms such as blockage/obstruction/congestion or nasal discharge with two or more symptoms such as nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior runny nose) plus facial pain/pressure and/or reduced or lost sense of smell sense of smell. Additionally, objective findings such as the presence of nasal polyps and/or nasal presence of nasal polyps and/or mucopurulent discharge in the middle meatus and/or edema or mucous or mucosal obstruction in the middle meatus on nasal endoscopy.

HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells.

Pancreatic cancer has a high mortality rate due to its aggressive nature and high metastatic rate. When coupled to the difficulties in detecting this type of tumor early and the lack of effective treatments, this cancer is currently one of the most important clinical challenges in the field of oncology. Melitherapy is an innovative therapeutic approach that is based on modifying the composition and structure of cell membranes to treat different diseases, including cancers. In this context, 2-hydroxycervonic acid (HCA) is a melitherapeutic agent developed to combat pancreatic cancer cells, provoking the programmed cell death by apoptosis of these cells by inducing ER stress and triggering the production of ROS species. The efficacy of HCA was demonstrated in vivo, alone and in combination with gemcitabine, using a MIA PaCa-2 cell xenograft model of pancreatic cancer in which no apparent toxicity was evident. HCA is metabolized by α-oxidation to C21:5n-3 (heneicosapentaenoic acid), which in turn also showed anti-proliferative effect in these cells. Given the unmet clinical needs associated with pancreatic cancer, the data presented here suggest that the use of HCA merits further study as a potential therapy for this condition.

MutSß regulates G4-associated telomeric R-loops to maintain telomere integrity in ALT cancer cells.

Up to 15% of human cancers maintain their telomeres through a telomerase-independent mechanism, termed "alternative lengthening of telomeres" (ALT) that relies on homologous recombination between telomeric sequences. Emerging evidence suggests that the recombinogenic nature of ALT telomeres results from the formation of RNA:DNA hybrids (R-loops) between telomeric DNA and the long-noncoding telomeric repeat-containing RNA (TERRA). Here, we show that the mismatch repair protein MutSß, a heterodimer of MSH2 and MSH3 subunits, is enriched at telomeres in ALT cancer cells, where it prevents the accumulation of telomeric G-quadruplex (G4) structures and R-loops. Cells depleted of MSH3 display increased incidence of R-loop-dependent telomere fragility and accumulation of telomeric C-circles. We also demonstrate that purified MutSß recognizes and destabilizes G4 structures in vitro. These data suggest that MutSß destabilizes G4 structures in ALT telomeres to regulate TERRA R-loops, which is a prerequisite for maintenance of telomere integrity during ALT.

Grado de satisfacción e impacto social y medioambiental en pacientes incluidos en un programa de seguimiento remoto de marcapasos / Degree of satisfaction and social and environmental impact in patients included in a remote pacemaker monitoring program

Resumen Objetivo: Describir el grado de satisfacción y el impacto sociolaboral y medioambiental de los pacientes de un programa de seguimiento remoto de marcapasos. Método: Estudio observacional prospectivo que incluyó 160 pacientes del programa de seguimiento remoto entre 2016 y 2017. Se pasó una encuesta de satisfacción a dichos pacientes y se cuantificó la disminución del CO2 emitido al reducir el número de visitas. Resultados: Los pacientes acudían acompañados (86%) y en coche (66%) la mayoría de las veces, y mostraron un grado de satisfacción «bueno o excelente¼ en un 96%. Se estima un ahorro de emisión de CO2 de casi un 10% por ciclo de seguimiento. Conclusiones: El seguimiento remoto de marcapasos implantado en nuestra unidad de arritmias reduce el impacto sociolaboral, económico y medioambiental.

Abstract Objective: To describe the degree of satisfaction and social, occupational and environmental impact of patients on our remote pacemaker monitoring programme run. Method: Prospective observational study including 160 patients on the remote pacemaker monitoring programme between 2016 and 2017. We handed out a satisfaction survey and quantified the decrease in CO2 emitted by reducing the number of visits. Results: The patients attended visits accompanied (86%) and by car (66%) most of the time. 96% of respondents said their degree of satisfaction was "good or excellent". We estimated a saving in CO2 emissions of almost 10% for each remote monitoring cycle. Conclusions: The remote monitoring of pacemakers implemented by our arrhythmia unit reduces the social, occupational, financial and environmental impact.

Effect of self-expandable metal stent on morbidity and mortality and oncological prognosis in malignant colonic obstruction: retrospective analysis of its use as curative and palliative treatment.

INTRODUCTION: Acute gastrointestinal obstruction due to colorectal cancer occurs in 7-30% of cases and is an abdominal emergency that requires urgent decompression. The safety and oncological effect of self-expandable metal stents (SEMS) in these patients remains controversial. This study aimed to evaluate its impact on these variables and compare it with that of emergency surgery (ES). METHODS: Descriptive, retrospective and single-centre study, performed between 2008 and 2015, with follow-up until 2017. One hundred eleven patients with diagnosis of left malignant colonic obstruction were included and divided according to the treatment received: stent as bridge to surgery (SBTS group: 39), palliative stent (PS group: 30) and emergency surgery with curative (ECS group: 34) or palliative intent (EPS group: 8). Treatment was decided by the attending surgeon in charge. RESULTS: Technical and clinical general success rates for colorectal SEMS were 95.7% and 91.3%, respectively, with an associated morbimortality of 23.2%, which was higher in the PS group (p = 0.002). The SBTS group presented a higher laparoscopic approach and primary anastomosis (p < 0.001), as well as a lower colostomy rate than the ECS group (12.8% vs. 40%; p = 0.023). Postoperative morbidity and mortality were significantly lower in the SBTS group compared to the ECS group (41% vs. 67.6%; p = 0.025). Overall survival (OS) and disease-free survival (DFS) were similar between the analysed groups. CONCLUSION: Colonic stent placement is a safe and effective therapeutic alternative to emergency surgery in the management of left-sided malignant colonic obstruction in both curative and palliative fields. It presents a lower postoperative morbimortality and a similar oncological prognosis.

Usefulness of peripheral blood monocyte count to predict relapse in patients with inflammatory bowel disease: a prospective longitudinal cohort study.

BACKGROUND: monocytes play an important role in the pathogenesis of inflammatory bowel disease but data are scarce regarding activity biomarkers, above all in patients under biologic therapies. OBJECTIVE: the aim of this study was to evaluate the value of monocyte measurements in predicting flares in inflammatory bowel disease patients under maintenance treatment with anti-TNF. METHODS: a prospective, observational cohort study was designed. Relapse was defined as a Harvey-Bradshaw score > 4 in Crohn's disease, and a partial Mayo score ≥ 2 in ulcerative colitis. Monocyte concentration was quantified at 4-month intervals for twelve months. A total of 95 consecutive patients were included. Median age was 42 years, 50.5 % were female, and 75 % had Crohn's disease. RESULTS: sixteen months after inclusion, 65 (68.4 %) patients remained in clinical remission. Mean monocyte count preceding a relapse was 563 (standard deviation: 144) compared to 405 (standard deviation: 177) in patients who remained in remission. Final monocyte count was significantly different between relapse and remission in Crohn's disease (0.82; 95 % CI: 0.71-0.90; p < 0.005). According to the multivariate analysis, only monocytes and fecal calprotectin were related to more relapses. CONCLUSION: in conclusion, in inflammatory bowel disease patients under anti-TNF therapy, repeat monocyte counts could help monitor patients, at least in Crohn's disease.

Celecoxib and Dimethylcelecoxib Block Oxidative Phosphorylation, Epithelial-Mesenchymal Transition and Invasiveness in Breast Cancer Stem Cells.

BACKGROUND: The major hurdles for successful cancer treatment are drug resistance and invasiveness developed by breast cancer stem cells (BCSC). OBJECTIVE: As these two processes are highly energy-dependent, the identification of the main ATP supplier required for stem cell viability may result advantageous in the design of new therapeutic strategies to deter malignant carcinomas. METHODS: The energy metabolism (glycolysis and oxidative phosphorylation, OxPhos) was systematically analyzed by assessing relevant protein contents, enzyme activities, and pathway fluxes in BCSC. Once identified as the main ATP supplier, selective energy inhibitors and canonical breast cancer drugs were used to block stem cell viability and metastatic properties. RESULTS: OxPhos and glycolytic protein contents, as well as HK and LDH activities were several times higher in BCSC than in their parental line, MCF-7 cells. However, CS, GDH, COX activities, and both energy metabolism pathway fluxes were significantly lower (38-86%) in BCSC than in MCF-7 cells. OxPhos was the main ATP provider (>85%) in BCSC. Accordingly, oligomycin (a specific and potent canonical OxPhos inhibitor) and other non-canonical drugs with inhibitory effect on OxPhos (celecoxib, dimethylcelecoxib) significantly decreased BCSC viability, levels of epithelial-mesenchymal transition proteins, invasiveness, and induced ROS over-production, with IC50 values ranging from 1 to 20 µM in 24 h treatment. In contrast, glycolytic inhibitors (gossypol, iodoacetic acid, 3-bromopyruvate, 2-deoxyglucose) and canonical chemotherapeutic drugs (paclitaxel, doxorubicin, cisplatin) were much less effective against BCSC viability (IC50> 100 µM). CONCLUSION: These results indicated that the use of some NSAIDs may be a promising alternative therapeutic strategy to target BCSC.

Lipids in Pathophysiology and Development of the Membrane Lipid Therapy: New Bioactive Lipids.

Membranes are mainly composed of a lipid bilayer and proteins, constituting a checkpoint for the entry and passage of signals and other molecules. Their composition can be modulated by diet, pathophysiological processes, and nutritional/pharmaceutical interventions. In addition to their use as an energy source, lipids have important structural and functional roles, e.g., fatty acyl moieties in phospholipids have distinct impacts on human health depending on their saturation, carbon length, and isometry. These and other membrane lipids have quite specific effects on the lipid bilayer structure, which regulates the interaction with signaling proteins. Alterations to lipids have been associated with important diseases, and, consequently, normalization of these alterations or regulatory interventions that control membrane lipid composition have therapeutic potential. This approach, termed membrane lipid therapy or membrane lipid replacement, has emerged as a novel technology platform for nutraceutical interventions and drug discovery. Several clinical trials and therapeutic products have validated this technology based on the understanding of membrane structure and function. The present review analyzes the molecular basis of this innovative approach, describing how membrane lipid composition and structure affects protein-lipid interactions, cell signaling, disease, and therapy (e.g., fatigue and cardiovascular, neurodegenerative, tumor, infectious diseases).

The Novel Antitumor Compound HCA Promotes Glioma Cell Death by Inducing Endoplasmic Reticulum Stress and Autophagy.

Glioblastoma (GBM) is the most common and aggressive type of primary brain tumor in adults, and the median survival of patients with GBM is 14.5 months. Melitherapy is an innovative therapeutic approach to treat different diseases, including cancer, and it is based on the regulation of cell membrane composition and structure, which modulates relevant signal pathways. Here, we have tested the effects of 2-hydroxycervonic acid (HCA) on GBM cells and xenograft tumors. HCA was taken up by cells and it compromised the survival of several human GBM cell lines in vitro, as well as the in vivo growth of xenograft tumors (mice) derived from these cells. HCA appeared to enhance ER stress/UPR signaling, which consequently induced autophagic cell death of the GBM tumor cells. This negative effect of HCA on GBM cells may be mediated by the JNK/c-Jun/CHOP/BiP axis, and it also seems to be provoked by the cellular metabolite of HCA, C21:5n-3 (heneicosapentaenoic acid). These results demonstrate the efficacy of the melitherapeutic treatment used and the potential of using C21:5n-3 as an efficacy biomarker for this treatment. Given the safety profile in animal models, the data presented here provide evidence that HCA warrants further clinical study as a potential therapy for GBM, currently an important unmet medical need.