A Strategic Synthesis of Orange Waste-Derived Porous Carbon via a Freeze-Drying Method: Morphological Characterization and Cytocompatibility Evaluation.

Porous carbon materials from food waste have gained growing interest worldwide for multiple applications due to their natural abundance and the sustainability of the raw materials and the cost-effective synthetic processing. Herein, orange waste-derived porous carbon (OWPC) was developed through a freeze-drying method to prevent the demolition of the original biomass structure and then was pyrolyzed to create a large number of micro, meso and macro pores. The novelty of this work lies in the fact of using the macro-channels of the orange waste in order to create a macroporous network via the freeze-drying method which remains after the pyrolysis steps and creates space for the development of different types of porous in the micro and meso scale in a controlled way. The results showed the successful preparation of a porous carbon material with a high specific surface area of 644 m2 g-1 without any physical or chemical activation. The material's cytocompatibility was also investigated against a fibroblast cell line (NIH/3T3 cells). OWPC triggered a mild intracellular reactive oxygen species production without initiating apoptosis or severely affecting cell proliferation and survival. The combination of their physicochemical characteristics and high cytocompatibility renders them promising materials for further use in biomedical and pharmaceutical applications.

Clinical Impact of C-myc Oncogenic Diversity on Solid and Lymphoid Malignancies.

INTRODUCTION: Onset and progression of malignant tumors is a multistep process including a variety of gross chromosomal and specific genes' deregulation. Among oncogenes that are frequently altered in solid and also in hematological malignancies, the C-myc (gene locus: 8q24.21) plays a pivotal role. C-myc is a proto-oncogene encoding for a nuclear phosphoprotein implicated in cell cycle progression, apoptosis and cellular differentiation and transformation. OBJECTIVE: The purpose of the current molecular review was to explore the differences of C-myc oncogenic activity in solid and lymphoid malignancies that modify its clinical impact on them. MATERIAL AND METHOD: A systematic review of the literature in the international database PubMed was carried out. The year 2010 was set as a prominent time limit for the publication date of articles in the majority of them, whereas specific references of great importance and historical value in the field of C-myc gene discovery and analysis were also included. The following keywords were used: C-myc, oncogene, signaling pathway, malignancies, carcinoma, lymphoma. A pool of 43 important articles were selected for the present study at the basis of combining molecular knowledge with new targeted therapeutic strategies. RESULTS: C-myc oncogene demonstrates two different mechanisms of deregulation: amplification, mutation and translocation patterns. These particular aspects of gene alteration are unique for solid and non-solid (hematological) malignancies, respectively. CONCLUSIONS: C-myc is characterized by diversity regarding its deregulation mechanisms in malignancies derived from different tissues. C-myc translocation is sporadically combined with amplification ("complicon" formation) or mutations creating exotic genetic signatures. This "bi-phasic" C-myc deregulation model in the corresponding malignant tumor categories clinically affects the corresponding patients, also modifying the targeted therapeutic strategies on them.

Comparative Analysis of External and Internal Radiotherapy- Dependent Plans in Patients with Gynecological Cancer.

Background/Aim: Radiotherapy plays a key role in the treatment of gynecological cancer. Modern radiotherapy techniques with external beams (e-RT) are applied in a broad spectrum of gynecological cancer cases. However, high radiation doses, affecting normal tissue adjacent to cancer, represent the main disadvantage of e-RT regimens. For this reason, brachytherapy (BT), an internal beam-based technique (i-RT), is suggested following e-RT. Our purpose was to compare e-RT plans using volumetric-modulated arc therapy (VMAT) with those using 3D conformal techniques (3D-CRT) and compare BT plans guided by 3D or 2D imaging based on the potential corresponding toxicity levels. Materials and Methods: In this preliminary, non-randomized comparative retrospective study, 15 females suffering gynecological cancer were enrolled. Modern e-RT and i-RT (BT) techniques were applied. Results: Concerning e-RT, D95/D99/rectum 2cc/bladder 2cc and small intestine 2cc were measured and compared; in i-RT, rectum 2cc/bladder 2cc were measured and compared. The median dose to the planning target volume in VMAT was 97.4 Gy compared with 92.9 Gy in 3D-CRT. Τhe rectum received almost 5 Gy less in VMAT compared to 3D-CRT (median of 43.5 Gy vs. 48.6 Gy; p=0.001). In the bladder, dose differences were minimal, while the small intestine received 47.6 Gy in VMAT (p=0.001). Regarding 3D-BT, the rectum received 63.1 Gy compared with 49.9 Gy (p=0.009) in 2D-BT. Concerning the bladder, mean 2D-BT and 3D-BT doses were 71.9 and 65 Gy, respectively, differing non-significantly. Conclusion: VMAT was found to be superior to 3D-CRT, especially in dose distribution, volume coverage and protection of critical organs. Similarly, 3D-BT should be preferred over 2D-BT due to critical advantages.

Graphene oxide and oxidized carbon nanodiscs as biomedical scaffolds for the targeted delivery of quercetin to cancer cells.

Targeting cancer cells without affecting normal cells poses a particular challenge. Nevertheless, the utilization of innovative nanomaterials in targeted cancer therapy has witnessed significant growth in recent years. In this study, we examined two layered carbon nanomaterials, graphene and carbon nanodiscs (CNDs), both of which possess extraordinary physicochemical and structural properties alongside their nano-scale dimensions, and explored their potential as nanocarriers for quercetin, a bioactive flavonoid known for its potent anticancer properties. Within both graphitic allotropes, oxidation results in heightened hydrophilicity and the incorporation of oxygen functionalities. These factors are of great significance for drug delivery purposes. The successful oxidation and interaction of quercetin with both graphene (GO) and CNDs (oxCNDs) have been confirmed through a range of characterization techniques, including FTIR, Raman, and XPS spectroscopy, as well as XRD and AFM. In vitro anticancer tests were conducted on both normal (NIH/3T3) and glioblastoma (U87) cells. The results revealed that the bonding of quercetin with GO and oxCNDs enhances its cytotoxic effect on cancer cells. GO-Quercetin and oxCNDs-Quercetin induced G0/G1 cell cycle arrest in U87 cells, whereas oxCNDs caused G2/M arrest, indicating a distinct mode of action. In long-term survival studies, cancer cells exhibited significantly lower viability than normal cells at all corresponding doses of GO-Quercetin and oxCNDs-Quercetin. This work leads us to conclude that the conjugation of quercetin to GO and oxCNDs shows promising potential for targeted anticancer activity. However, further research at the molecular level is necessary to substantiate our preliminary findings.

Firing Alterations of Neurons in Alzheimer's Disease: Are They Merely a Consequence of Pathogenesis or a Pivotal Component of Disease Progression?

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, yet its underlying causes remain elusive. The conventional perspective on disease pathogenesis attributes alterations in neuronal excitability to molecular changes resulting in synaptic dysfunction. Early hyperexcitability is succeeded by a progressive cessation of electrical activity in neurons, with amyloid beta (Aß) oligomers and tau protein hyperphosphorylation identified as the initial events leading to hyperactivity. In addition to these key proteins, voltage-gated sodium and potassium channels play a decisive role in the altered electrical properties of neurons in AD. Impaired synaptic function and reduced neuronal plasticity contribute to a vicious cycle, resulting in a reduction in the number of synapses and synaptic proteins, impacting their transportation inside the neuron. An understanding of these neurophysiological alterations, combined with abnormalities in the morphology of brain cells, emerges as a crucial avenue for new treatment investigations. This review aims to delve into the detailed exploration of electrical neuronal alterations observed in different AD models affecting single neurons and neuronal networks.

Comparative Expression Analysis of TP53 Tumor Suppressor and MDM2 Oncogene in Colorectal Adenocarcinoma.

Background/Aim: The tumor protein 53 (TP53) tumor suppressor protein (17p13.1) acts as a significant regulator for the cell cycle normal function. The gene is frequently mutated in colorectal adenocarcinoma (CRC) patients and is associated to poor prognosis and low response rates to chemo-targeted therapy. Our purpose was to correlate TP53 expression with Mouse Double Minute 2 Homolog (MDM2), a proto-oncogene (12q14.3) and a major negative regulator in the TP53-MDM2 auto-regulatory pathway. Materials and Methods: A total of forty (n=40) colorectal adenocarcinoma (CRC) cases were included in this study. An immunohistochemistry-based assay was implemented by using anti-TP53 and anti-MDM2 antibodies in the corresponding tissue sections. Additionally, a digital image analysis assay was implemented for objectively measuring TP53/MDM2 immunostaining intensity levels. Results: TP53 protein overexpression was detected in 27/40 (67.5%), whereas MDM2 overexpression in 28/40 (70%) cases. Interestingly, in 21/40 (52.5%) cases, a combined TP53/MDM2 co-expression was detected, whereas in 6/40 (15%), a combined loss of expression was identified (overall co-expression: p=0.119). p53 overexpression was significantly correlated to grade of the examined cases (p=0.001), whereas MDM2 to stage and max diameter of the malignancies (p=0.001 and 0.024, respectively). Conclusion: TP53/MDM2 over expression is a frequent and significant genetic event in CRCs associated with an aggressive biological behavior, as a result of increased dedifferentiation grade and advanced stage/elevated tumor volume, respectively. MDM2 oncogene overactivation combined with mutated and overexpressed TP53 is observed in sub-groups of patients leading to specific gene/protein signatures - targets for personalized chemotherapeutic approaches.

Longitudinal Muscle Biopsies Reveal Inter- and Intra-Subject Variability in Cancer Cachexia: Paving the Way for Biopsy-Guided Tailored Treatment.

In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research.

Glioblastoma research on zebrafish xenograft models: a systematic review

Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal model for preclinical GBM xenograft studies without a standardized methodology. This systematic review aims to summarize the advances in zebrafish GBM xenografting, compare research protocols to pinpoint advantages and underlying limitations, and designate the predominant xenografting parameters. Based on the PRISMA checklist, we systematically searched PubMed, Scopus, and ZFIN using the keywords “glioblastoma,” “xenotransplantation,” and “zebrafish” for papers published from 2005 to 2022, available in English. 46 articles meeting the review criteria were examined for the zebrafish strain, cancer cell line, cell labeling technique, injected cell number, time and site of injection, and maintenance temperature. Our review designated that AB wild-type zebrafish, Casper transparent mutants, transgenic Tg(fli1:EGFP), or crossbreeding of these predominate among the zebrafish strains. Orthotopic transplantation is more commonly employed. A number of 50–100 cells injected at 48 h post-fertilization in high density and low infusion volume is considered as an effective xenografting approach. U87 cells are used for GBM angiogenesis studies, U251 for GBM proliferation studies, and patient-derived xenograft (PDX) to achieve clinical relevance. Gradual acclimatization to 32–33 °C can partly address the temperature differential between the zebrafish and the GBM cells. Zebrafish xenograft models constitute valuable tools for preclinical studies with clinical relevance regarding PDX. The GBM xenografting research requires modification based on the objective of each research team. Automation and further optimization of the protocol parameters could scale up the anticancer drug trials (AU)

Developmental Dyslexia: Insights from EEG-Based Findings and Molecular Signatures-A Pilot Study.

Developmental dyslexia (DD) is a learning disorder. Although risk genes have been identified, environmental factors, and particularly stress arising from constant difficulties, have been associated with the occurrence of DD by affecting brain plasticity and function, especially during critical neurodevelopmental stages. In this work, electroencephalogram (EEG) findings were coupled with the genetic and epigenetic molecular signatures of individuals with DD and matched controls. Specifically, we investigated the genetic and epigenetic correlates of key stress-associated genes (NR3C1, NR3C2, FKBP5, GILZ, SLC6A4) with psychological characteristics (depression, anxiety, and stress) often included in DD diagnostic criteria, as well as with brain EEG findings. We paired the observed brain rhythms with the expression levels of stress-related genes, investigated the epigenetic profile of the stress regulator glucocorticoid receptor (GR) and correlated such indices with demographic findings. This study presents a new interdisciplinary approach and findings that support the idea that stress, attributed to the demands of the school environment, may act as a contributing factor in the occurrence of the DD phenotype.

Enhancement of the biological activity of hydroxytyrosol through its oxidation by laccase from Trametes versicolor.

The laccase-catalyzed oxidation of hydroxytyrosol (HT) towards the formation of its bioactive oligomer derivatives was investigated. The biocatalytic oligomerization was catalyzed by laccase from Trametes versicolor in aqueous or various water-miscible organic solvents and deep eutectic solvent (DES)-based media. Mass Spectroscopy and Nuclear Magnetic Resonance were used for the characterization of the products. The solvent system used significantly affects the degree of HT oligomerization. The use of 50 % v/v methanol favored the production of the HT dimer, while other organic solvents as well as DESs led to the formation of hydroxytyrosol trimer and other oligomers. In vitro studies showed that the HT dimer exhibits 3- to 4-fold enhanced antibacterial activity against Gram-positive and Gram-negative bacteria compared to the parent compound. Moreover, the ability of HT dimer to inhibit the activity of soybean lipoxygenase and Candida rugosa lipase was 1.5-fold higher than HT, while molecular docking supported these results. Furthermore, HT dimer showed reduced cytotoxicity against HEK293 cells and exhibited a strong ability to inhibit ROS formation. The enhanced bioactivity of HT dimer indicates that this compound could be considered for use in cosmetics, skin-care products, and nutraceuticals.

PTEN Deregulation Mechanisms in Salivary Gland Carcinomas.

Among the tumour suppressor genes that affect critically cell functions and homeostasis, phosphatase and tensin homolog deleted in chromosome 10 (PTEN- gene locus: 10q21) regulates the PI3K/Akt/mTOR signalling pathway. PTEN is deleted, mutated or epigenetically hyper-methylated in a variety of human solid malignancies. Salivary gland carcinomas (SGCs) belong to the head and neck carcinomas (HNCs) super category of solid malignancies. Histo-pathologically, they demonstrate a significant diversity due to a variety of distinct and mixed subtypes. Genetically, they are characterized by a broad spectrum of gene and chromosomal imbalances. Referring specifically to suppressor genes, PTEN deregulation plays a critical role in signaling transduction in the corresponding SGC pre- and malignant epithelia modifying the response rates to potential targeted therapeutic strategies. In the current review, we explored the role of PTEN deregulation mechanisms that are involved in the onset and progression of SGCs.

Cell replacement therapy with stem cells in multiple sclerosis, a systematic review.

Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination and axonal loss. It is induced by attack of autoreactive lymphocytes on the myelin sheath and endogenous remyelination failure, eventually leading to accumulation of neurological disability. Disease-modifying agents can successfully address inflammatory relapses, but have low efficacy in progressive forms of MS, and cannot stop the progressive neurodegenerative process. Thus, the stem cell replacement therapy approach, which aims to overcome CNS cell loss and remyelination failure, is considered a promising alternative treatment. Although the mechanisms behind the beneficial effects of stem cell transplantation are not yet fully understood, neurotrophic support, immunomodulation, and cell replacement appear to play an important role, leading to a multifaceted fight against the pathology of the disease. The present systematic review is focusing on the efficacy of stem cells to migrate at the lesion sites of the CNS and develop functional oligodendrocytes remyelinating axons. While most studies confirm the improvement of neurological deficits after the administration of different stem cell types, many critical issues need to be clarified before they can be efficiently introduced into clinical practice.

Glioblastoma research on zebrafish xenograft models: a systematic review.

Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal model for preclinical GBM xenograft studies without a standardized methodology. This systematic review aims to summarize the advances in zebrafish GBM xenografting, compare research protocols to pinpoint advantages and underlying limitations, and designate the predominant xenografting parameters. Based on the PRISMA checklist, we systematically searched PubMed, Scopus, and ZFIN using the keywords "glioblastoma," "xenotransplantation," and "zebrafish" for papers published from 2005 to 2022, available in English. 46 articles meeting the review criteria were examined for the zebrafish strain, cancer cell line, cell labeling technique, injected cell number, time and site of injection, and maintenance temperature. Our review designated that AB wild-type zebrafish, Casper transparent mutants, transgenic Tg(fli1:EGFP), or crossbreeding of these predominate among the zebrafish strains. Orthotopic transplantation is more commonly employed. A number of 50-100 cells injected at 48 h post-fertilization in high density and low infusion volume is considered as an effective xenografting approach. U87 cells are used for GBM angiogenesis studies, U251 for GBM proliferation studies, and patient-derived xenograft (PDX) to achieve clinical relevance. Gradual acclimatization to 32-33 °C can partly address the temperature differential between the zebrafish and the GBM cells. Zebrafish xenograft models constitute valuable tools for preclinical studies with clinical relevance regarding PDX. The GBM xenografting research requires modification based on the objective of each research team. Automation and further optimization of the protocol parameters could scale up the anticancer drug trials.

Heat Shock Proteins' Expression Profiles in Odontogenic Ameloblastomas and Cysts.

Tumors and cysts with odontogenic origin represent a family of lesions with specific histo-genetic and clinical characteristics. Among them, ameloblastomas are common benign neoplasms, predominantly detected in the anatomic areas of the jaws and also in the mandible and maxilla. Although they are characterized by a slow and stable growing pattern, a subset of them shows a tendency for local tissue invasiveness and partially increased recurrence rates after surgical excision. Furthermore, heat shock proteins (HSPs) are potentially implicated in ameloblastoma onset and progression. HSPs regulate the folding and refolding of proteins and are induced in response to oxidative stress. They are crucial members of the chaperone intracellular system and are categorized based on their molecular weight (i.e., HSP27, HSP60, HSP70, HSP90). In the current review, we describe HSPs origin and function, focusing on their deregulation mechanisms and impact predominantly on ameloblastomas and also on inflammatory and developmental odontogenic cystic lesions.

Effect of Highly Hydrophilic Superparamagnetic Iron Oxide Nanoparticles on Macrophage Function and Survival.

Superparamagnetic iron oxide nanoparticles (SPIONs) have garnered significant attention in the medical sector due to their exceptional superparamagnetic properties and reliable tracking capabilities. In this study, we investigated the immunotoxicity of SPIONs with a modified surface to enhance hydrophilicity and prevent aggregate formation. The synthesized SPIONs exhibited a remarkably small size (~4 nm) and underwent surface modification using a novel "haircut" reaction strategy. Experiments were conducted in vitro using a human monocytic cell line (THP-1). SPIONs induced dose-dependent toxicity to THP-1 cells, potentially by generating ROS and initiating the apoptotic pathway in the cells. Concentrations up to 10 µg/mL did not affect the expression of Nrf2, HO-1, NF-κB, or TLR-4 proteins. The results of the present study demonstrated that highly hydrophilic SPIONs were highly toxic to immune cells; however, they did not activate pathways of inflammation and immune response. Further investigation into the mechanisms of cytotoxicity is warranted to develop a synthetic approach for producing effective, highly hydrophilic SPIONs with little to no side effects.

Impact of Amplified Oncogenes on Salivary Gland Carcinomas.

In normal epithelia, proto-oncogenes regulate critical intra- or intercellular functions, including cell growth and proliferation, apoptosis, and signaling transduction from the cell periphery (extracellular space) to the nucleus mediated by different pathways. Oncogenes are the mutated or amplified forms of the corresponding proto-oncogenes that are crucially involved in cell neoplastic and malignant transformation during carcinogenesis. Salivary gland carcinomas (SGCs) demonstrate a variety of histogenetic types. They are characterized by a broad spectrum of chromosomal and gene alterations. In particular, amplifications in specific genes [human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 4 (HER4), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), Mouse double minute 2 homolog (MDM2), androgen receptor (AR), programmed death (ligand 1 (PD-L1), neurogenic differentiation factor 2 (NEUROD2), phosphatidylinositol 3,4,5-trisphosphate-dependent RAC exchanger 1 protein (PREX1), cyclin-dependent kinase4/6 (CDK4/6), proline-rich acidic protein 1 (PRAP1), kell antigen system (KEL), glutamate receptor subunit epsilon 2 (GRIN2D), Ewing sarcoma RNA-binding protein 1 (EWSR1), MYC proto-oncogene (MYC)] combined or not with chromosomal numerical imbalances (aneuploidy/ polysomy/monosomy) form different genetic signatures affecting the response to monoclonal antibody-based, oncologicaly targeted regimens. Different SGC histotypes demonstrate specific combinations of mutated/amplified genes that modify their clinicohistological features. In the current molecular review, we present the most important amplified oncogenes and their impact on the biological behavior of SGCS.

Hydroxytyrosol produced by engineered Escherichia coli strains activates Nrf2/HO-1 pathway: An in vitro and in vivo study.

This study explores the biological effects of hydroxytyrosol (HT), produced by the metabolic engineering of Escherichia coli, in a series of in vitro and in vivo experiments. In particular, a metabolically engineered Escherichia coli strain capable of producing HT was constructed and utilized. HEK293 and HeLa cells were exposed to purified HT to determine non-toxic doses that can offer protection against oxidative stress (activation of Nrf2/HO-1 signaling pathway). Male CD-1 mice were orally supplemented with HT to evaluate (1) renal and hepatic toxicity, (2) endogenous system antioxidant response, and (3) activation of Nrf2/HO-1 system in the liver. HT protected cells from oxidative stress through the activation of Nrf2 regulatory network. Activation of Nrf2 signaling pathway was also observed in the hepatic tissue of the mice. HT supplementation was safe and produced differential effects on mice's endogenous antioxidant defense system. HT biosynthesized from genetically modified Escherichia coli strains is an alternative method to produce high-quality HT that exerts favorable effects in the regulation of the organism's response to oxidative stress. Nonetheless, further investigation of the multifactorial action of HT on the antioxidant network regulation is needed.

Mutational Signatures in Salivary Gland Carcinomas.

Salivary gland carcinomas belong to the head and neck carcinoma super category of malignancies. They are characterized by histopathological diversity and comprise a variety of entities and subtypes. Mucoepidermoid, adenoid cystic and salivary duct carcinomas represent the most prominent malignancies. Concerning their corresponding genetic background, a broad spectrum of gene and chromosomal imbalances has been detected. Point mutations and deletions, amplifications and translocations, combined or not with chromosomal aneuploidy/polysomy/monosomy, create a landscape of specific genetic signatures that affect the biological behavior of these tumors and modify response rates to potential targeted therapeutic strategies. In the current molecular review, we focused on the categorization and description of the most important mutational signatures in salivary gland carcinomas.

Cellular Localization of Orexin 1 Receptor in Human Hypothalamus and Morphological Analysis of Neurons Expressing the Receptor.

The orexin system is related to food behavior, energy balance, wakefulness and the reward system. It consists of the neuropeptides orexin A and B, and their receptors, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). OX1R has selective affinity for orexin A, and is implicated in multiple functions, such as reward, emotions, and autonomic regulation. This study provides information about the OX1R distribution in human hypothalamus. The human hypothalamus, despite its small size, demonstrates a remarkable complexity in terms of cell populations and cellular morphology. Numerous studies have focused on various neurotransmitters and neuropeptides in the hypothalamus, both in animals and humans, however, there is limited experimental data on the morphological characteristics of neurons. The immunohistochemical analysis of the human hypothalamus revealed that OX1R is mainly found in the lateral hypothalamic area, the lateral preoptic nucleus, the supraoptic nucleus, the dorsomedial nucleus, the ventromedial nucleus, and the paraventricular nucleus. The rest of the hypothalamic nuclei do not express the receptor, except for a very low number of neurons in the mammillary bodies. After identifying the nuclei and neuronal groups that were immunopositive for OX1R, a morphological and morphometric analysis of those neurons was conducted using the Golgi method. The analysis revealed that the neurons in the lateral hypothalamic area were uniform in terms of their morphological characteristics, often forming small groups of three to four neurons. A high proportion of neurons in this area (over 80%) expressed the OX1R, with particularly high expression in the lateral tuberal nucleus (over 95% of neurons). These results were analyzed, and shown to represent, at the cellular level, the distribution of OX1R, and we discuss the regulatory role of orexin A in the intra-hypothalamic areas, such as its special role in the plasticity of neurons, as well as in neuronal networks of the human hypothalamus.

Calpain-mediated Mechanoptosis in Breast Adenocarcinoma.

Calpains belong to a family of important calcium-dependent cysteine proteases. They are involved in intracellular processes including cytoskeleton disorganization and substrate proteolysis. They also enhance apoptosis and cell to cell adhesion. Calpains demonstrate also a mechanosensory function in neoplastic and malignant cells due to their implication in mechanoptosis. This is a specific type of apoptotic death induced by strong external mechanical stimuli. Anti-cytoskeleton rigidity inhibition strategies based on calpain induction lead to increased apoptosis of tumor transformed cells. Elevated intracellular calcium concentration mediated by specific receptors and channels activates calpains. In the current molecular review, we explored the role of calpains in calcium-dependent signa transduction pathways in breast adenocarcinoma in conjunction with novel agents that activate their important anti-tumor functions.