Histology and histopathology Vol.36, nº1 (2021)
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- PublicationOpen AccessFragmentation of the Golgi complex of dopaminergic neurons in human substantia nigra: new cytopathological findings in Parkinson's disease(Universidad de Murcia. Departamento de Biología Celular e Histología, 2021) Tomás, Mónica; Martínez Martínez, Narcisa; Cara Esteban, Mireia; Martínez Alonso, Emma; Martínez Menárguez, José ÁngelFragmentation of the Golgi ribbon is a common feature of Parkinson's disease and other neurodegenerative diseases. This alteration could be the consequence of the anterograde and retrograde transport imbalance, α-synuclein aggregates, and/or cytoskeleton alterations. Most information on this process has been obtained from cellular and animal experimental models, and as such, there is little information available on human tissue. If the information on human tissue was available, it may help to understand the cytopathological mechanisms of this disease. In the present study, we analyzed the morphological characteristics of the Golgi complex of dopaminergic neurons in human samples of substantia nigra of control and Parkinson's disease patients. We measured the expression levels of putative molecules involved in Golgi fragmentation, including α-synuclein, tubulin, and Golgi-associated regulatory and structural proteins. We show that, as a consequence of the disease, the Golgi complex is fragmented into small stacks without vesiculation. We found that only a limited number of regulatory proteins are altered. Rab1, a small GTPase regulating endoplasmic reticulum-to-Golgi transport, is the most dramatically affected, being highly overexpressed in the surviving neurons. We found that the SNARE protein syntaxin 5 forms extracellular aggregates resembling the amyloid plaques characteristic of Alzheimer's disease. These findings may help to understand the cytopathology of Parkinson's disease.
- PublicationOpen AccessIn Memoriam: Professor Francisco Hernández-Calvo (1931-2020)(2021) Díaz Flores, Lucio; Madrid Cuevas, Juan Francisco
- PublicationOpen AccessOutside-in signaling by femoral cuff injury induces a distinct vascular lesion in adipose triglyceride lipase knockout mice(Universidad de Murcia. Departamento de Biología Celular e Histología, 2021) Noguchi, Hirotsugu; Yamada, Sohsuke; Hirano, Ken Ichi; Yamaguchi, Satoshi; Suzuki, Akira; Guo, Xin; Zaima, Nobuhiro; Li, Ming; Kobayashi, Kunihisa; Ikeda, Yoshihiko; Nakayama, Toshiyuki; Sasaguri, YasuyukiGenetic deficiency of adipose triglyceride lipase (ATGL), a rate-limiting enzyme for intracellular triglyceride (TG) hydrolysis, causes TG-deposit cardiomyovasculopathy (TGCV), a recently identified rare cardiovascular disorder (ORPHA code: 565612) in humans. One of the major characteristics of TGCV is a novel type of diffuse and concentric coronary atherosclerosis with ATGL-deficient smooth muscle cells (SMCs). Patients with TGCV have intractable coronary artery disease. Therefore, it is crucial to investigate the mechanisms underlying vascular lesions in ATGL deficiency using animal models. Cuff injury is an experimental procedure to induce vascular remodeling with neointimal formation with SMCs after placing a cuff around the adventitial side of the artery without direct influence on endothelium. We report the effect of cuff injury on femoral arteries of ATGLknockout (ATGL–/–) mice. Cuff-induced concentric neointimal formation with migrating SMCs was exacerbated in ATGL–/– mice, mimicking atherosclerotic lesions in patients with TGCV. In the media, cell death of SMCs and loss of elastic fibers increased. Perivascular infiltrating cells expressing tumor necrosis factor-α (TNF-α) were more prominent in ATGL–/– mice than in wild-type (WT) mice. In Boyden chamber experiments, a greater number of ATGL–/– SMCs migrated in response to TNF-α compared to WT SMCs. These data, for the first time, demonstrated that outsidein signaling by cuff-induced neointimal formation where paracrine stimuli from adventitial infiltrating cells may lead to neointimal formation and mediolysis in ATGLdeficient conditions. Cuff injury might be a valuable model for understanding the mechanisms underlying the development of atherosclerotic lesions in patients with TGCV
- PublicationOpen AccessIdentifying specific Notch1 target proteins in lung carcinoma cells(Universidad de Murcia. Departamento de Biología Celular e Histología, 2021) Hassan, Wael Abdo; Ito, TakaakiBackground. The Notch signaling pathway has different roles in many human neoplasms, being either tumor-promoting or anti-proliferative. In addition, Notch signaling in carcinogenesis can be tissue dependent. The aim of the current study is to elucidate the relation between Notch1 protein expression in lung cancer cells and the following Notch related proteins: Hes1, c-Myc, Jagged1 and Jagged2. Methods. Notch1 and its related proteins were detected in human lung cancer cell lines and in 54 surgically resected different lung carcinoma tissues. Then, we used small interfering RNA (siRNA) technology, to down-regulate the expression of Notch1 in H69AR and SBC3 small cell lung carcinoma (SCLC) cells. Also, we transfected venus Notch1 intracellular domain (v.NICD) plasmid into human SCLC lines; H69. Results. The expression of Hes1, c-Myc and Jagged2 is affected by Notch1 in SCLC. Conclusion. There is a strong association between the expression of Notch1 protein and the expression of Hes1, c-Myc and Jagged2 proteins, which could aid in better understanding tumorigenesis in SCLC.
- PublicationOpen AccessImmunology of tissue homeostasis, ovarian cancer growth and regression, and long lasting cancer immune prophylaxis - review of literature(Universidad de Murcia. Departamento de Biología Celular e Histología, 2021) Bukovsky, AntoninData on the substantial physiological role of the immune system in the organism’s ability to manage proper differentiation and function of normal tissues (tissue homeostasis), and detailed causes of the immune system’s essential role for the in vivo stimulation of cancer growth, are severely lacking. This results in a lack of effective cancer immunotherapy without adverse events, and in the lack of long-lasting cancer immune prophylaxes, particularly in ovarian cancers. Elimination of blood auto-antibodies blocking anti-cancer T cell effectors by intermittent moderate doses of cyclophosphamide, facilitation of the immune system reactivity against alloantigens of cancer cells by two subsequent blood transfusions, and augmentation of anticancer immunity by weekly intradermal injections of bacterial toxins, caused during the subsequent treatmentfree period, lasting for two to four weeks, regression of inoperable epithelial ovarian cancers and regeneration of the tremendously metastatically altered abdominal tissues into normal healthy conditions without multivisceral cytoreductive surgery, which can result in life-threatening consequences. An otherwise untreated rectal cancer, progressing over 3 years, regressed after severe toxic dermatitis lasting over one week. This was caused by an accidental consumption of a large raw shiitake mushroom. Subsequent daily consumptions of 2 g Metformin ER and honeybee propolis ethanol extract, and weekly single larger raw shiitake mushroom, which all stimulate immune system reactivity against cancer stem cells, prevented malignant recurrence over the next 29 years without recurring dermatitis, and maintained healthy organism’s conditions. These observations indicate that regression of advanced inoperable cancers and long-lasting cancer immune prophylaxis can be reached by simple approaches