Grigoraş A

Ovarian cancer: insights into genetics and pathogeny.

Starting from the information on ovarian cancer provided by the mainstream publications, we construct a review focusing on the following issues: (i) the genetic profile, (ii) the role of the epithelial-mesenchymal transition in the acquirement of malignant features, (iii) the controversial hypothesis regarding the origin, and (iv) the involvement of the immune system in the tumoral microenvironment. Advances in the decipherment at the genetic level in the pathogenic mechanisms progressively lead to the idea of a genetic signature for the ovarian cancer. Moreover, the complementary approaches oriented towards the decryption of the intrinsic structure of the expressed molecules and, implicitly, the development of proteomics open new perspectives for an early diagnosis and an appropriate treatment. The research on the epithelial-mesenchymal transition (mainly those exploring the signaling pathways responsible for the switch between the loss of the epithelial characteristics and the gain of a mesenchymal cell phenotype, with results in the amplification of differentiation, motility and tumoral invasion) allow a deeper understanding of the complex pathogenic mechanism which governs ovarian carcinogenesis. The classic conception of ovarian cancer pathogeny, based on the role of the ovarian surface epithelium, is currently reconsidered, and a novel hypothesis is formulated, which supports direct involvement of the Fallopian tubes for the serous type. Although recent research suggests the implication of immune/inflammatory cells by specific mechanisms in ovarian cancer pathogenesis, there is yet reliable evidence concerning their modality of direct action and/or modulation of tumoral growth. Thus, ovarian carcinogenesis remains a research challenge, due to still numerous unknown factors involved in the malignant transformation sequences, originating from the genetic-molecular alterations and reflected by cellular and tissue expression patterns.

Adipocytes spectrum — From homeostasia to obesity and its associated pathology

Firstly identified by anatomists, the fat tissue is nowadays an area of intense research due to increased global prevalence of obesity and its associated diseases. Histologically, there are four types of fat tissue cells which are currently recognized (white, brown, beige, and perivascular adipocytes). Therefore, in this study we are reviewing the most recent data regarding the origin, structure, and molecular mechanisms involved in the development of adipocytes. White adipocytes can store triglycerides as a consequence of lipogenesis, under the regulation of growth hormone or leptin and adiponectin, and release fatty acids resulted from lipolysis, under the regulation of the sympathetic nervous system, glucocorticoids, TNF-α, insulin, and natriuretic peptides. Brown adipocytes possess a mitochondrial transmembrane protein thermogenin or UCP1 which allows heat generation. Recently, thermogenic, UCP positive adipocytes have been identified in the subcutaneous white adipose tissue and have been named beige adipocytes. The nature of these cells is still controversial, as current theories are suggesting their origin either by transdifferentiation of white adipocytes, or by differentiation from an own precursor cell. Perivascular adipocytes surround most of the arteries, exhibiting a supportive role and being involved in the maintenance of intravascular temperature. Thoracic perivascular adipocytes resemble brown adipocytes, while abdominal ones are more similar to white adipocytes and, consequently, are involved in obesity-induced inflammatory reactions. The factors involved in the regulation of adipose stem cells differentiation may represent potential pathways to inhibit or to divert adipogenesis. Several molecules, such as pro-adipogenic factors (FGF21, BMP7, BMP8b, and Cox-2), cell surface proteins or receptors (Asc-1, PAT2, P2RX5), and hypothalamic receptors (MC4R) have been identified as the most promising targets for the development of future therapies. Further investigations are necessary to complete the knowledge about adipose tissue and the development of a new generation of therapeutic tools based on molecular targets.

Periostin in bronchial asthma – a brief update

Periostin is an extracellular matrix protein which intervenes in the regulation of angiogenesis, and in tumoral cells proliferation and invasion. Recent studies, mainly experimental models, have demonstrated the intervention of this molecule in asthmatic disease, by eosinophils recruitment, bronchial wall remodeling, and by stimulation of inflammatory cytokines production. Currently, periostin is considered a marker of type 2 inflammation in asthma, being secreted by respiratory epithelial cells triggered by IL-13 and IL-4. Concomitantly, periostin accumulated at the bronchial epithelial-connective tissue interface is involved in fibrogenesis and mucus secretion, in correlation with the intensity of bronchial mucosa eosinophilic inflammatory infiltrate. However, the intimate molecular mechanisms of periostin involvement in the pathogenic pathway of asthmatic diseases is far away from elucidation, further research being necessary to certify its value as a biomarker useful in diagnosis and in establishment of therapeutic schemes in bronchial asthma.

Cryptogenic organizing pneumonia - a rare lung condition

Cryptogenic organizing pneumonia is characterized by excessive proliferation of granulation tissue within small airways and alveolar ducts associated with chronic inflammation in the surrounding alveoli. Complete resolution occurs in 65-85% of patients treated with corticosteroid therapy, and recurrence is not uncommon. Within this context, we present the case of a 60 year-old men who died in same day after admission in hospital. Standard microscopy of necroptic specimens revealed edema, vascular congestion, interstitial lung fibrosis, buds of endoalveolar connective tissue and an inflammatory infiltrate in bronchiolar wall. The histopathological examination provides a better understanding of clinical symptoms that lead to dead in this case.

Multiorganic fat embolism in a case of post-traumatic fracture of the humerus

Fat embolism syndrome is a known complication in traumatology, especially in long bone fractures. The incidence of the fat embolism syndrome depends on the bone involved, whether fractures are isolated or multiple, the age of the patient, and the gender. It rarely occurs as a result of medical conditions. Classically, patients presents with a triad consisting of pulmonary distress, mental status changes, and petechial rash, occurred 24 to 48 hours after long-bone fracture. We present the case of an 88 year old woman, a victim of a traffic accident (pedestrian), who died in the same day. Autopsy and microscopic examination of fragments of tissue stained with Sudan III confirmed the presence of a multiorganic fat embolism in this case of post-traumatic fracture of the humerus.