Interrelation of Hypoxia-Inducible Factor-1 Alpha (HIF-1 α) and the Ratio between the Mean Corpuscular Volume/Lymphocytes (MCVL) and the Cumulative Inflammatory Index (IIC) in Ulcerative Colitis.

We intended to investigate the presence and medical application of serum hypoxia-inducible factor-1 alpha (HIF-1α) along with the already known systemic inflammatory markers and the new one's inflammatory indices, the proportion of mean corpuscular volume and lymphocytes (MCVL) and the cumulative inflammatory index (IIC), for patients with ulcerative colitis (UC). We sought to establish correlations that may be present between the serum levels of HIF-1α and these inflammatory indices, as well as their relationship with disease activity and the extent of UC, which can provide us with a more precise understanding of the evolution, prognosis, and future well-being of patients. Serum samples were collected from 46 patients diagnosed with UC and 23 controls. For our assessment of the serum levels of HIF-1α, we used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. Thus, for HIF-1α we detected significantly higher values in more severe and more extensive UC. When it came to MCVL and IIC, we observed statistically significant differences between the three groups being compared (Severe, Moderate, and Mild). Our study highlighted that HIF-1α correlated much better with a disease activity score, MCVL, and IIC. With MCVL and IIC, a strong and very strong correlation had formed between them and well-known inflammation indices. By examining the ROC curves of the analyzed parameters, we recognized that TWI (accuracy of 83.70%) provides the best discrimination of patients with early forms of UC, followed by HIF-1α (73.90% accuracy), MCVL (70.90% accuracy), and PLR (70.40%). In our study, we observed that HIF-1α, MCVL, and PLR had the same sensitivity (73.33%) but HIF-1α had a much better specificity (60.87% vs. 58.70%, and 54.35%). Also, in addition to the PLR, HIF-1α and MCVL can be used as independent predictor factors in the discrimination of patients with early forms of UC.

New insights into IL-17/IL-23 signaling in ankylosing spondylitis (Review).

Ankylosing spondylitis (AS) is a progressive common autoimmune inflammatory disease, part of the spondylarthritis group, characterized, besides clinical spinal and peripheral joint inflammation, by enthesitis and new bone formation, that can lead to severe functional impairment. Beyond intensive and continuous research on the pathogenic process extensively performed in recent years, their impact on therapeutic management remains open to future development. Better knowledge of AS pathogenesis have shown results progressively and studies are being performed to advance our current understanding of the disease. It is well known that tumor necrosis factor (TNF) exerts a central role, along with interleukin-17 (IL-17) and interleukin-23 (IL-23), demonstrated by several clinical studies. Similar to other rheumatic inflammatory conditions, SA is associated with an early process of systemic bone loss, both trabecular and cortical, consecutive osteopenia, osteoporosis, and high fracture risk. Current personalized therapeutic options benefit from new published data, to prevent future complications and to improve quality of life.

JAK/STAT pathway in pathology of rheumatoid arthritis (Review).

Rheumatoid arthritis (RA) is classified as an inflammatory, chronic autoimmune and disabling disease based on the intricate interplay between environmental and genetic factors. With a prevalence ranging from 0.3 to 1%, RA is the most prevalent inflammatory joint disease observed in adults. Disruption of immune tolerance becomes evident when abnormal stimulation of the innate and adaptive immune system occurs. This cascade of events causes persistent joint inflammation, proliferative synovitis and, ultimately, damage of the underlying cartilage as well as the subchondral bone, leading to permanent joint destruction, deformity and subsequent loss of function. With cytokines being the key to a multitude of biological processes, including inflammation, hematopoiesis and overall immune response, one must inevitably look at the main pathways through which a significant number of those molecules exert their function. Janus kinase/signal transducers and activators of transcription (JAK/STATs) represent one such pathway and, recently, JAK inhibitors (JAKinibs) have shown promise in the treatment of several inflammatory diseases, including RA. This narrative review focuses on the intricate signaling pathways involved as well as on the clinical aspects and safety profiles of JAKinibs approved for the treatment of RA.

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.

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.