Host immune response in chronic hepatitis C infection: involvement of cytokines and inflammasomes.

Chronic liver disease is a major health issue worldwide and chronic hepatitis C (CHC) is associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC). There is evidence that the hepatitis C virus (HCV) infection is correlated with immune senescence by way of immune activation and chronic inflammation, which lead to increased metabolic and cardiovascular risk, as well as progressive liver damage. Both the innate and adaptive immunity are firmly tied to the prognosis of an infection with HCV and its response to antiviral therapy. HCV is therefore associated with increased pro-inflammatory status, heightened production of cytokines, prolonged systemic inflammation, as well as increased morbidity and mortality, mainly due to the progression of hepatic fibrosis and HCC, but also secondary to cardiovascular diseases. Viral hepatic pathology is increasingly considered a disease that is no longer merely limited to the liver, but one with multiple metabolic consequences. Numerous in vitro studies, using experimental models of acute or chronic inflammation of the liver, has brought new information on immunopathological mechanisms resulting from viral infections and have highlighted the importance of involving complex structures, inflammasomes complex, in these mechanisms, in addition to the involvement of numerous proinflammatory cytokines. Beyond obtaining a sustained viral response and halting the aforementioned hepatic fibrosis, the current therapeutic "treat-to-target" strategies are presently focused on immune-mediated and metabolic disorders, to improve the quality of life and long-term prognosis of CHC patients.

The role of mediating factors involved in angiogenesis during implantation.

Angiogenesis is a critical component of normal implantation and placentation and underlines the importance of vascularization in early pregnancy. Differentiated expression of angiogenesis factors in different decision tissues during different stages of implantation, indicates their involvement in the regulation of vascular remodeling and angiogenesis. Disorders in vascular development may play a role in the pathogenesis of recurrent abortions. The success of implantation, placentation and subsequent pregnancy evolution requires coordination of vascular development and adaptations at both sides of the maternal-fetal interface. The human implantation process is a continuous process, which begins with the apposition and attachment of the blastocyst to the apical surface of the luminal endometrial epithelium and continues throughout the first trimester of pregnancy until the extravillous trophoblast invades and remodels maternal vascularization. Numerous regulatory molecules play functional roles in many processes, including preparation of the endometrial stroma (decidualization), epithelium for implantation, control of trophoblastic adhesion and invasion. These regulatory molecules include cytokines, chemokines, and proteases, many of which are expressed by different cell types, having slightly different functions as the implant progresses.

Toxicity and health impact of nanoparticles. Basic biology and clinical perspective.

Stroke has limited restorative treatment options. In search of new therapeutic strategies for the ischemic brain, cell-based therapies offered new hope, which has been, in the meanwhile, converted into a more realistic approach recognizing difficulties related to unfavorable environments causing low survival rates of transplanted neuronal precursors. Stem cell therapies are based on the transplantation of neuronal precursor cells (NPCs), adult stem cells propagated in cell culture or inducible pluripotent cells (iPSCs) obtained from patients and trans-differentiated into neural cells. Of these, autologous iPSCs have the advantage to be used in stroke patients because they do not raise ethical concerns and the risk of graft rejection is low. However, the use of stem cells for stroke therapy in humans has to take into account many factors including, dosage, route of administration, toxicity and side effects. For example, nanoparticles (NPs) may increase the efficacy of drugs and therapeutic cells delivery to the diseased brain. Medication dosages are generally determined by clinical trials done in relatively young, healthy people. However, in vivo and clinical data evaluating the toxic effects of NPs on neural cells are still scarce especially in the aged brain, which has a decreased homeostatic capacity and a reduced ability to cope with internal and environmental stress, as compared to the young brain. Previous studies in rodents indicate that aging along with neurodegenerative diseases may promote a proinflammatory state and leads to the development of gliosis in the aged brains. On the other hand, the nonspecific interaction between the shell of NPs and brain proteins leads to the adsorption of opsonins on their surface, forming the so-called "corona", thereby becoming ideal candidates to attract phagocytic microglia resulting in NPs engulfment and thus exacerbating neuronal death. Therefore, when designing NPs for clinical use, it should be considered that their systemic administration is associated with potential risks, especially in the aged subjects. Recently, NPs have been shown in recent years to play a crucial role in cell signaling processes involved in stroke recovery. Extracellular vesicles (EVs) are secreted by virtually all type of cells in the body and have been shown to reflect the physiological and metabolic status of the host cells. Thus, understanding the disease-specific contents of EVs would enable the discovery of novel predictive biomarkers.

Serological and immunohistochemical biomarkers for discrimination between benign and malignant ovarian tumors.

BACKGROUND: Ovarian tumors are difficult to diagnose because symptoms are nonspecific, occurring in late stages when the tumor mass reaches large proportions, when complications arise or when dissemination occurs in neighboring organs. Research over the past decades has been aimed at clarifying the mechanisms of ovarian oncogenesis, to identify ways of transforming normal cells into a neoplastic cell, as well as discovering of tumor markers used in the detection of neoplastic processes, along with the synthesis of therapeutic substances, which would influence its development. AIMS: In our study, we aimed to determine the serum concentrations of cancer antigen 125 (CA125), human epididymis protein 4 (HE4) and the risk of ovarian malignancy algorithm (ROMA) in patients with ovarian tumors, as well as assessing their diagnostic performance. Furthermore, another objective of the study was to identify a concordant relation between serological and immunohistochemical (IHC) biomarkers in supporting and aiding the differentiation between benign and malignant tumors, here including the group of borderline tumors. PATIENTS, MATERIALS AND METHODS: We accomplished a study that included a group of 92 patients diagnosed with ovarian tumors (benign and malignant), who were examined and treated between January 2015 and July 2018. The study was conducted at the Clinics of Obstetrics and Gynecology, "Filantropia" Municipal Hospital of Craiova, Romania. The patients were divided into two groups: the group of patients with benign tumors, subdivided into pre-menopausal (51 cases, 55.43%) and post-menopausal (30 cases, 32.6%) patients, and a group of patients who presented with malignant formation (seven cases with malignant tumors, 7.61% and four cases with borderline tumors, 4.34%, respectively). In parallel, we investigated 35 women as control subjects, who did not have a personal history of ovarian tumors. RESULTS: In our study, we have observed that for the analyzed parameters, CA125, HE4, and the ROMA index, significantly higher serum concentrations were detected in the malignant tumor group, when these have been compared to the values obtained for the pre-menopausal and for the post-menopausal subgroup, respectively. The IHC results also showed different expression patterns for the different markers studied. Corroboration of the results of the serological biomarkers with the IHC data is necessary and useful for differentiating borderline tumors and for their final integration as benign or malignant ovarian tumors. This can only be done for the cases with surgical resections, thus having tissue available. CONCLUSIONS: The serum levels of CA125 and HE4, ROMA index and IHC markers for surgical tissue fragments play a very important role in discriminating and reporting borderline ovarian tumors, as well as benign or malignant ovarian forms. Due to the superior sensitivity and specificity of CA125 and HE4, we can consider these markers as an alternative or additional diagnostic criterion to the ROMA index.

Determination of VEGFR-2 (KDR) -604A>G polymorphism in recurrent pregnancy loss.

BACKGROUND: Placental angiogenesis and vascular adaptation during pregnancy, along with diminished placental trophoblastic vascular endothelial growth factor immunoreactivity, play an important role in the early stages of human pregnancy, being possible causes of recurrent pregnancy loss (RPL). AIMS: Our focus was directed towards investigating a possible association between vascular endothelial growth factor receptor-2 (kinase insert domain receptor) VEGFR-2 (KDR) -604A>G (rs 2071559) gene polymorphism and RPL in the study area of Dolj County, Romania. PATIENTS, MATERIALS AND METHODS: In this study, 169 women, diagnosed with RPL, were included. They were hospitalized in the Clinics of Obstetrics and Gynecology, "Filantropia" Municipal Hospital, Craiova, during the following period: October 2009-October 2016. The control group consisted of 145 women. All subjects were genotyped by means of allelic discrimination TaqMan polymerase chain reaction assay with specific probes. RESULTS: No statistically significant difference was observed between the RPL patients and the control group, when one genotype was compared to another [in a dominant model, -604 AG+GG vs. AA: odds ratio (OR) 1.71, 95% confidence interval (CI) 0.99-2.96, p=0.051]. While studying the overall risk of RPL by the genotype frequencies of KDR polymorphism between controls and RPL patients, which were stratified according to the number of consecutive pregnancy losses (PLs), the chi-square test showed a significant association between the presence of this polymorphism and the increased risk observed in patients with four or more consecutive PLs, to develop RPL (in a dominant model - G allele carriers, KDR -604 AG+GG vs. AA: OR 1.91, 95% CI 1.03-3.52, p=0.037). These results prove that G allele carriers have an increased risk of RPL about 1.91-fold higher than those with the AA genotype do. Although our results bear limited statistical significance, the study nonetheless represents a step forward in the evaluation of recurrent abortion, which has not yet been explored sufficiently. CONCLUSIONS: VEGFR-2 (KDR) polymorphism does not influence RPL susceptibility in the study area of Dolj County, Romania. Therefore, further studies, which include a larger sample size, are required in order to clarify the role of KDR polymorphism in RPL.