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Obesity is defined as an increase in the number and size of the adipocytes. Nutrient overload causes the adipocyte to secrete its own cytokines and attract more macrophages, exacerbating the inflammatory process. Neuro-inflammation has been associated with many neurodegenerative diseases and is considered a critical promoter of cognitive impairment. Alliin, the main organosulfide compound in garlic, has demonstrated potential medicinal properties. However, its anti-inflammatory potential in the brain has not yet been studied. The aim was to evaluate the effect of alliin on the expression of inflammatory markers in different brain regions after diet-induced obesity. The mice were divided into 5 groups (n=5): normal weight with standard diet (GC), obese (GO), and three concentrations of alliin (GE1-3) fed with high fat diet (HFD) for 8 weeks to induce obesity, after this period, the GE1-3 groups were supplemented with alliin (1, 5 and 10 mg/kg weight) for 5 weeks. At week 13 the mice were stimulated with LPS, then sacrificed and the brains were dissected. The gene expression of pro-inflammatory cytokines in different brain regions was determined by RT-qPCR and analyzed by the 2-ΔΔCT method. The expression of the analyzed cytokines was higher in the hippocampus. In addition, the 1 mg dose of alliin induces a greater response, and higher doses induce a reduction in the expression of IL1-β, IL-6 and TNF-α, except in the case of MCP-1, which with higher doses increased its relative expression. In conclusion, Alliin can act as an immunomodulatory molecule on the expression of cytokines involved in brain inflammation. [ABSTRACT FROM AUTHOR]

Cancer is a global health issue, increasingly prevalent and a leading cause of mortality. Despite extensive research, conventional treatments remain aggressive, often damaging healthy cells, and exhibit limited efficacy. Addressing drug resistance and enhancing treatment effectiveness are critical challenges in advancing cancer therapy. This review examines the potential of natural plant compounds, particularly phytochemicals and their derivatives, in developing novel anticancer agents. These metabolites have a long history in traditional medicine, with 42% of molecules approved for cancer treatment between 1981 and 2019 being either natural products or derivatives. The Cactaceae family, which comprises more than 1,500 species, represents a largely untapped source of potentially useful chemopreventive and anticancer agents. Although more than 3,000 plants and their derivatives have contributed to chemotherapeutic development, cactus species have received limited attention until recently. Emerging evidence highlights the anticancer potential of fruits, stems, and cladodes from various cactus species. This review provides a comprehensive and current overview of experimental studies on Cactaceae in cancer research, aiming to pave the way for the development of innovative, natural cancer therapeutics and contribute to the ongoing battle against this formidable disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Orozco-Barocio, Sánchez-Sánchez, Rojas-Mayorquín, Godínez-Rubí, Reyes-Mata and Ortuño-Sahagún.)

Background: There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the expression of C4d in FSGS subtypes in percutaneous native renal biopsies in a second-level hospital and its correlation with clinical, biochemical and histological variables., Material and Methods: A retrospective study in paraffin blocks of patients with biopsy with FSGS aged 16-65 years, indistinct sex, not diabetic or obese. Immunohistochemistry was performed for C4d and their expression was analyzing in non-sclerosed glomerular capillaries (GC) and sclerosis areas (SA). Clinical and biochemical variables were recorded. The cases were divided into C4d positive and C4d negative groups and compared. The correlation between C4d staining scores in CG and SA with clinical and biochemical variables were analyzed., Results: Twenty samples were analyzed, 4 for each subtype. At the time of biopsy average age 38.8 ± 18.6 years, 65% male, 8.7% were hypertension. The percentage of positivity for C4d was 40% in GC, 30% SA and 35% in mesangium. The highest expression was for cellular and collapsing subtypes. C4d positivity cases had increased proteinuria (p = 0.035). A significant correlation was found between percentage of C4d expression in CG with SA (p = 0.012) and SA with tubular atrophy and interstitial fibrosis (p < 0.05)., Conclusions: C4d expression in FSGS predominated in the cellular and collapsing subtypes, which translates complement activation. C4d is a possible surrogate marker in GSFS., (Copyright © 2023 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Cervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express phenotypic markers like fibroblast activation protein (FAP), vimentin, S100A4, α-smooth muscle actin (αSMA), and functional markers such as MMP9. This study aimed to evaluate the protein expression of vimentin, S100A4, αSMA, FAP, and MMP9 in mesenchymal stem cells (MSC)-CAF cells, as well as in cervical cancer samples. MSC cells were stimulated with HeLa and SiHa tumor cell supernatants, followed by protein evaluation and cytokine profile to confirm differentiation towards a CAF phenotype. In addition, automated immunohistochemistry (IHQa) was performed to evaluate the expression of these proteins in CC samples at different stages. Our findings revealed a high expression of FAP in stimulated MSC cells, accompanied by the secretion of pro/anti-inflammatory cytokines. In the other hand, CC samples were observed to have high expression of FAP, vimentin, αSMA, and MMP9. Most importantly, there was a high expression of their activation proteins αSMA and FAP during the different stages. In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA- FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression.

Prostate cancer (PCa) is the most prevalent cause of death in the male population worldwide. The G Protein-Coupled Estrogen Receptor (GPER) has been gaining relevance in the development of PCa. Hedgehog (Hh) pathway activation is associated with aggressiveness, metastasis, and relapse in PCa patients. To date, no studies have evaluated the crosstalk between the GPER and the Hh pathway along different group grades in PCa. We conducted an analysis of paraffin-embedded tissues derived from patients with different prognostic grade of PCa using immunohistochemistry. Expression and correlation between GPER and glioma associated oncogene homologue (GLI) transcriptional factors in the parenchyma and stroma of PCa tumors were evaluated. Our results indicate that GPER is highly expressed in the nucleus and increases with higher grade groups. Additionally, GPER's expression correlates with pGLI3 nuclear expression across different grade groups in PCa tissues; however, whether the receptor induces the activation of GLI transcriptional factors, or the latter modulate the expression of GPER is yet to be discovered, as well as the functional consequence of this correlation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rico-Fuentes, López-Pulido, Pérez-Guerrero, Godínez-Rubí, Villegas-Pineda, Villanueva-Pérez, Sierra-Díaz, Zepeda-Nuño, Pereira-Suárez and Ramírez-de-Arellano.)

YKL-40 increase according to the aging process, and its functions have been associated with tissue remodeling and systemic inflammation. In Rheumatoid Arthritis (RA) it has been proposed as a possible biomarker of activity and severity, however; in the field of idiopathic inflammatory myopathies (IIM) the role of YKL-40 in IIM is not clear. Thus, we aimed to evaluate if there is an association between the serum levels and muscle tissue expression of YKL-40 with age, IIM phenotype, muscle strength and myositis disease activity. The main finding was that age is the most important variable that affects the YKL-40 serum levels. In muscle biopsy, we observed that YKL-40 is mainly expressed in infiltrating lymphoid cells than in muscle tissue. Using ANCOVA according to the b-coefficients, YKL-40 serum levels are predicted by inflammatory state, age, and IIM diagnosis., (© 2023. The Author(s).)

During embryonic and fetal development, the cerebellum undergoes several histological changes that require a specific microenvironment. Pleiotrophin (PTN) has been related to cerebral and cerebellar cortex ontogenesis in different species. PTN signaling includes PTPRZ1, ALK, and NRP-1 receptors, which are implicated in cell differentiation, migration, and proliferation. However, its involvement in human cerebellar development has not been described so far. Therefore, we investigated whether PTN and its receptors were expressed in the human cerebellar cortex during fetal and early neonatal development. The expression profile of PTN and its receptors was analyzed using an immunohistochemical method. PTN, PTPRZ1, and NRP-1 were expressed from week 17 to the postnatal stage, with variable expression among granule cell precursors, glial cells, and Purkinje cells. ALK was only expressed during week 31. These results suggest that, in the fetal and neonatal human cerebellum, PTN is involved in cell communication through granule cell precursors, Bergmann glia, and Purkinje cells via PTPRZ1, NRP-1, and ALK signaling. This communication could be involved in cell proliferation and cellular migration. Overall, the present study represents the first characterization of PTN, PTPRZ1, ALK, and NRP-1 expression in human tissues, suggesting their involvement in cerebellar cortex development.

The muscle fiber ultrastructure in Idiopathic Inflammatory Myopathies (IIM) has been scarcely explored, especially in Inclusion Body Myositis. The aim of this study was to implement the Scanning Electron Microscopy (SEM) in a small cohort of IIM patients, together with the characterization of immunological profile for a better understanding of the pathophysiology. For immunological profile characterization, we identified the presence of autoantibodies (Ro-52, OJ, EJ, PL7, PL12, SRP, Jo-1, PMScl75, PMScl100, Ku, SAE1, NXP2, MDA5, TIF1γ, Mi-2α, Mi-2β) and quantified cytokines (IL-1β, IFN-α2, IFN-γ, TNF-α, IL-6, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33) and chemokines (CCL2, CXCL8). The histological analysis was made by hematoxylin-eosin staining while the muscle fiber ultrastructure was characterized by SEM. We observed changes in the morphology and structure of the muscle fiber according to muscle strength and muscle enzymes. We were able to find and describe muscle fiber ultrastructure with marked irregularities, porosities, disruption in the linearity and integrity of the fascicle, more evident in patients with increased serum levels of muscle enzymes and diminished muscle strength. Despite the scarce reports about the use of SEM as a tool in all clinical phenotypes of IIM, our work provides an excellent opportunity to discuss and reframe the clinical usefulness of SEM in the diagnostic approach of IIM., (© 2022. The Author(s).)

Cancer is an increasingly common disease and is considered one of the main causes of death in the world. Lophocereus schottii ( L. schottii ) is a cactus used in Mexico in traditional medicine for cancer treatment. This study aimed to determine the effect of the ethanolic extract and the polar and nonpolar fractions of L. schottii in murine L5178Y lymphoma cells in vitro , analyzing their effect on the proliferative activity of splenocytes, and establishing the effective concentration 50 (EC 50 ) of the polar fraction. In addition, the secondary metabolites present in the extracts were determined by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The study establishes that the three extracts of L. schottii have a cytotoxic effect on L5178Y cells and on the splenocytes stimulated with ConA. Additionally, the polar fraction has a significantly greater effect being three times more effective than cyclophosphamide on inhibiting the viability of L5178Y cells. Secondary metabolites present are mainly flavonoids and alkaloids, but there are also some terpenoids and sterols. Ultimately, polar fraction can be considered an anticancer substance, since its EC 50 of 15 μg/mL is within the parameters established by the National Cancer Institute., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Orozco-Barocio, Robles-Rodríguez, Camacho-Corona, Méndez-López, Godínez-Rubí, Peregrina-Sandoval, Rivera, Rojas Mayorquín and Ortuno-Sahagun.)

Pregnancy is a unique immunological condition in which an "immune-diplomatic" dialogue between trophoblasts and maternal immune cells is established to protect the fetus from rejection, to create a privileged environment in the uterus and to simultaneously be alert to any infectious challenge. The maternal-placental-fetal interface (MPFI) performs an essential role in this immunological defense. In this review, we will address the MPFI as an active immuno-mechanical barrier that protects against viral infections. We will describe the main viral infections affecting the placenta and trophoblasts and present their structure, mechanisms of immunocompetence and defensive responses to viral infections in pregnancy. In particular, we will analyze infection routes in the placenta and trophoblasts and the maternal-fetal outcomes in both. Finally, we will focus on the cellular targets of the antiviral microRNAs from the C19MC cluster, and their effects at both the intra- and extracellular level., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Macrophage migration inhibitory factor (MIF) has been associated with the pathogenesis of several rheumatic diseases. In systemic sclerosis (SSc) it has been shown that MIF expression is dysregulated in serum and skin. However, the MIF receptor, CD74, has been poorly investigated and its potential role in the pathogenesis of SSc remains unknown. This study aimed to analyze mRNA, tissue, and serum expression of MIF and CD74 in patients with limited (lcSSc) and diffuse (dcSSc) systemic sclerosis. A case-control study in 20 SSc patients and 20 control subjects (CS) from southern México was conducted. MIF and CD74 mRNA expression levels were quantified by real-time PCR, MIF serum levels were measured by an ELISA kit, and MIF and its receptor CD74 were evaluated by immunohistochemistry of skin biopsies. MIF mRNA expression was significantly higher in CS than in SSc patients (p = 0.02), while CD74 showed no differences between patients and CS. MIF serum levels were similar between SSc patients and CS: dcSSc = 3.82 ng/ml, lcSSc = 3.57 ng/ml, and CS = 3.28 ng/ml. In skin biopsies of SSc, MIF and CD74 were enhanced in keratinocytes, while they showed decreased expression in endothelial cells. On the other hand, the staining of CD74 was high in fibroblasts of dcSSc patients. Our findings show MIF and CD74 deregulation at the transcriptional and translational levels in SSc, which might be associated with the proinflammatory process leading to tissue remodeling and excessive fibrosis in SSc., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Termedia.)

Maternal ethanol consumption during pregnancy is one of the main causes of Neurodevelopmental disorders (NDD). Prenatal alcohol exposure (PAE) produces several adverse manifestations. Even low or moderate intake has been associated with long-lasting behavioral and cognitive impairment in offspring. In this study we examined the gene expression profile in the rat nucleus accumbens using microarrays, comparing animals exposed prenatally to ethanol and controls. Microarray gene expression showed an overall downward regulatory effect of PAE. Gene cluster analysis reveals that the gene groups most affected are related to transcription regulation, transcription factors and homeobox genes. We focus on the expression of the C-X-C motif chemokine ligand 16 ( Cxcl16 ) which was differentially expressed. There is a significant reduction in the expression of this chemokine throughout the brain under PAE conditions, evidenced here by quantitative polymerase chain reaction qPCR and immunohistochemistry. Chemokines are involved in neuroprotection and implicated in alcohol-induced brain damage and neuroinflammation in the developing central nervous system (CNS), therefore, the significance of the overall decrease in Cxcl16 expression in the brain as a consequence of PAE may reflect a reduced ability in neuroprotection against subsequent conditions, such as excitotoxic damage, inflammatory processes or even hypoxic-ischemic insult.

MicroRNAs (miRNAs) are small noncoding RNAs that function as epigenetic modulators regulating almost any gene expression. Similarly, other noncoding RNAs, as well as epigenetic modifications, can regulate miRNAs. This reciprocal interaction forms a miRNA-epigenetic feedback loop, the deregulation of which affects physiological processes and contributes to a great diversity of diseases. In the present review, we focus on miR-615, a miRNA highly conserved across eutherian mammals. It is involved not only during embryogenesis in the regulation of growth and development, for instance during osteogenesis and angiogenesis, but also in the regulation of cell growth and the proliferation and migration of cells, acting as a tumor suppressor or tumor promoter. It therefore serves as a biomarker for several types of cancer, and recently has also been found to be involved in reparative processes and neural repair. In addition, we present the pleiad of functions in which miR-615 is involved, as well as their multiple target genes and the multiple regulatory molecules involved in its own expression. We do this by introducing in a comprehensible way the reported knowledge of their actions and interactions and proposing an integral view of its regulatory mechanisms.

Background: Pericoronal radiolucent lesions are a common radiographic finding, but it is rare that they occur in multiple forms. Multiple calcifying hyperplastic dental follicles (MCHDF) are entities with few cases described to date; nevertheless, they appear to have a very particular phenotypic pattern., Cases Presentation: Case 1: A 10-year-old male was evaluated radiographically, revealing four impacted canines, each accompanied by unilocular pericoronal radiolucency. Case 2: A 16-year-old male was planning orthodontic treatment; following his radiological evaluation all third molars were found to be accompanied with pericoronal radiolucencies. Enucleation, and third molar removal along with the pericoronal tissue were the respective treatments. Microscopically, in both cases, the specimens shown odontogenic epithelium, and type I and II calcifications in the hyperplastic follicles, all these characteristics were consistent with MCHDF., Conclusion: Although MCHDF are a rare entity, they must be considered in the differential diagnosis of multiple pericoronal lesions. Under the light of the current evidence, the histological findings may be relatively heterogeneous, but their integration with both the clinical data, which are apparently particular, and with the radiographic characteristics, can lead to a definitive diagnosis.

Obesity generates a chronic low-grade inflammatory state which promotes oxidativestress and triggers comorbidities. Alliin is the main organosulfur compound in garlic and has beenshown to induce a decrease in the expression of proinflammatory cytokines; its systemic effect onmetabolic parameters and adipose tissue is not yet known, however. After nine weeks of HFD andwith obesity established in C57BL/6 mice, we observed that a daily treatment with alliin for 3.5weeks (15 mg/kg) did not affect body weight, but significantly improved insulin sensitivity andglucose tolerance, both evaluated through a blood glucose monitoring system. Once alliin treatmentwas completed, serum, adipose tissue, and organs of interest related to metabolism were removedfor further analysis. We observed that alliin significantly decreased the size of adipocytes fromepididymal adipose tissue, evaluated via microscopy. A decrease in gene expression and serumprotein levels of the adipocytokines leptin and resistin, as well as decreased serum IL-6concentration, were detected by qRT-PCR and ELISA, respectively. It did not, however, affectmRNA expression of antioxidant enzymes in the liver. Taken altogether, these results indicate thattreatment with alliin reduces metaflammation markers in DIO mice and improves some metabolicparameters without affecting others.

Objective: Trigeminal neuralgia (TN) is a neuropathic disorder that can be treated surgically. This study aimed to present the surgical findings and the clinical outcomes of 26 patients with TN treated by minimally invasive asterional surgery., Methods: Longitudinal descriptive study. Twenty-six patients with TN underwent minimally invasive asterional surgery. The medical history, surgical findings, therapeutic response, and complications were registered. They were followed for 36 months., Results: Nineteen cases were associated with vascular compression; five were associated with arachnoiditis. The two remaining cases were associated with multiple sclerosis and post-herpetic neuralgia. The pain was substantially reduced in all patients in the immediate postoperative period. At 36 months, in 25 patients, total or acceptable pain control was achieved. In the long term, 22 patients evolved with no permanent complications., Conclusion: The microvascular decompression surgery by an asterional approach is an alternative with similar results to the classic retrosigmoid approach to treat TN, but that adds the benefits of the principles of minimally invasive surgery. Constant efforts need to be made to optimize minimally invasive surgical techniques for TN., (Copyright: © 2019 Permanyer.)

Objective: Trigeminal neuralgia (TN) is a neuropathic disorder that can be treated surgically. This study aimed to present the surgical findings and the clinical outcomes of 26 patients with TN treated by minimally invasive asterional surgery., Methods: Longitudinal descriptive study. Twenty-six patients with TN underwent minimally invasive asterional surgery. The medical history, surgical findings, therapeutic response, and complications were registered. They were followed for 36 months., Results: Nineteen cases were associated with vascular compression; five were associated with arachnoiditis. The two remaining cases were associated with multiple sclerosis and post-herpetic neuralgia. The pain was substantially reduced in all patients in the immediate postoperative period. At 36 months, in 25 patients, total or acceptable pain control was achieved. In the long term, 22 patients evolved with no permanent complications., Conclusion: The microvascular decompression surgery by an asterional approach is an alternative with similar results to the classic retrosigmoid approach to treat TN, but that adds the benefits of the principles of minimally invasive surgery. Constant efforts need to be made to optimize minimally invasive surgical techniques for TN., (Copyright: © 2019 SecretarÍa de Salud.)

Objective: The purpose of the present study was to describe an OrBitoZygomatic (OBZ) surgical variant that implies the drilling of the orbital roof and lateral wall of the orbit without orbitotomy., Methods: Design : cross-sectional study. Between January 2010 and December 2014, 18 patients with middle fossa lesions underwent the previously mentioned OBZ surgical variant. Gender, age, histopathological diagnosis, complications, and percentage of resection were registered. The detailed surgical technique is described., Results: Of the 18 cases listed in the study, nine were males and nine females. Seventeen cases (94.5%) were diagnosed as primary tumoral lesions, one case (5.5%) presented with metastasis of a carcinoma, and an additional one had a fibrous dysplasia. Age ranged between 27 and 73 years. Early complications were developed in four cases, but all of these were completely resolved. None developed enophthalmos., Conclusion: The present study illustrates a novel surgical OBZ approach that allows for the performance of a simpler and faster procedure with fewer complications, and without increasing surgical time or cerebral manipulation, for reaching lesions of the middle fossa. Thorough knowledge of the anatomy and surgical technique is essential for successful completion of the procedure.

Background: Multiple myeloma is a plasmatic cell neoplasm that is characterized by skeletal destruction, renal failure, anemia and hypercalcemia. The skull plasmacytomas represent less than 1% of the head and neck tumors, they can be the primary lesion or occur as a secondary manifestation of multiple myeloma in 20-30% of the patients, or they can even manifest several years later after the diagnosis of plasmacytoma. Although some of the lesions may be surgically accessible, the aggressive natural behavior will complicate the evolution of the patients. We present two cases of Mexican women with intracranial plasmacytomas, one of them associated with multiple myeloma., Clinical Cases: The first case was a 24 year-old woman diagnosed with a multiple myeloma with plasmacytic-plasmablastic bone infiltration that was removed in 90%. She presented a local recurrence that required a second intervention for removal. The second case was a 62 year-old female with a malignant intracranial tumor of plasma cells that was totally resected. Both patients received adjuvant treatment based on chemotherapy and radiation therapy with favorable results. The patients died at 5 and 1.5 years respectively due to renal failure secondary to systemic disease., Conclusions: We propose chemotherapy and radiation therapy as an essential part of treatment for this condition, as the aggressive behavior of the neoplasms can complicate the evolution, despite being surgically accessible.

Purpose: The aim of this study was to assess the use of a new medical device to elevate depressed skull fractures (DSFs) in newborns and minor infants., Methods: Nine patients (ranging from 1 day to 9 months of age) with simple DSF underwent skull elevation by a new elevator medical device. This medical device comprises two elements: a pediatric resuscitator (CPR mask) connected to a 50-ml syringe. Pediatric CPR face mask is placed on the depressed region and negative pressure is generated through syringe plunger elevation until fracture reduction is observed., Results: Fracture reduction was confirmed in eight of nine patients by computed tomography scan without underlying brain damage and associated complications. Skull asymmetry was eliminated recovering normal shape. Up to now, there are no neurological concerns. Another treatment was chosen to be applied for one patient who did not respond to manipulation., Conclusion: The new device is a safe, affordable, and effective choice in the treatment of simple depressed skull fractures in newborns and minor infants.

Cerebral ischemia initiates a cascade of detrimental events including glutamate-associated excitotoxicity, intracellular calcium accumulation, formation of Reactive oxygen species (ROS), membrane lipid degradation, and DNA damage, which lead to the disruption of cellular homeostasis and structural damage of ischemic brain tissue. Cerebral ischemia also triggers acute inflammation, which exacerbates primary brain damage. Therefore, reducing oxidative stress (OS) and downregulating the inflammatory response are options that merit consideration as potential therapeutic targets for ischemic stroke. Consequently, agents capable of modulating both elements will constitute promising therapeutic solutions because clinically effective neuroprotectants have not yet been discovered and no specific therapy for stroke is available to date. Because of their ability to modulate both oxidative stress and the inflammatory response, much attention has been focused on the role of nitric oxide donors (NOD) as neuroprotective agents in the pathophysiology of cerebral ischemia-reperfusion injury. Given their short therapeutic window, NOD appears to be appropriate for use during neurosurgical procedures involving transient arterial occlusions, or in very early treatment of acute ischemic stroke, and also possibly as complementary treatment for neurodegenerative diseases such as Parkinson or Alzheimer, where oxidative stress is an important promoter of damage. In the present paper, we focus on the role of NOD as possible neuroprotective therapeutic agents for ischemia/reperfusion treatment.

A randomized clinical trial is a prospective experiment to compare one or more interventions against a control group, in order to determine the effectiveness of the interventions. A clinical trial may compare the value of a drug vs. placebo. It may compare surgical with medical interventions. The principles apply to any situation in which the issue of who is exposed to which condition is under the control of the experimenter, and that the method of assignment is through randomization. A negative clinical trial is that in which no significant difference is found between the comparison groups. Results without statistical difference may be useful either to discard useless treatments or to demonstrate that one intervention is as effective as the one it was compared with. Eliminating useless treatments may be adequate. However, if this is the result of studies with methodological errors, new interventions that are actually useful may not be available for patients. In this review we present some of the possible methodological errors that may lead to false negative results in clinical trials.