Emerging roles of HOTAIR lncRNA in the pathogenesis and prognosis of cardiovascular diseases.

Highlights HOTAIR, a long noncoding RNA, plays a role in the regulation of proteins involved in the pathogenesis of cardiovascular disease. Furthermore, it has been identified as a biomarker of this type of disease. Several factors and cells contribute to atherosclerosis, a progressive disease. However, the prognosis of HOTAIR in this disease varies depending on the path in which it plays a role. For this condition, there is no single prognosis to consider.

The Role of Rosavin in the Pathophysiology of Bone Metabolism.

Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor κ B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant attention in the neuroscience and oncological community regarding its neuroimmunomodulatory and oncogenic functions. This review of the literature summarizes and updates contemporary knowledge about PGRN, its associated receptors and signalling pathway involvement in GBM pathogenesis, indicating possible cellular and molecular mechanisms with potential diagnostic, prognostic and therapeutic targets in order to yield successful individual therapeutic strategies. After a review of the literature, we found that there are possible PGRN-targeted therapeutic approaches for implementation in GBM treatment algorithms both in preclinical and future clinical studies. Furthermore, PGRN-targeted therapies exerted their highest efficacy in combination with other established chemotherapeutic agents, such as temozolomide. The results of the analysis suggested that the possible implementation of routine determinations of PGRN and its associated receptors in tumour tissue and biofluids could serve as a diagnostic and prognostic biomarker of GBM. Furthermore, promising preclinical applications of PGRN-related findings should be investigated in clinical studies in order to create new diagnostic and therapeutic algorithms for GBM treatment.

lncRNA TUG1 as potential novel biomarker for prognosis of cardiovascular diseases.

Globally, cardiovascular diseases (CVDs) are among the leading causes of death. In light of the high prevalence and mortality of CVDs, it is imperative to understand the molecules involved in CVD pathogenesis and the signaling pathways that they initiate. This may facilitate the development of more precise and expedient diagnostic techniques, the identification of more effective prognostic molecules and the identification of potential therapeutic targets. Numerous studies have examined the role of lncRNAs, such as TUG1, in CVD pathogenesis in recent years. According to this review article, TUG1 can be considered a biomarker for predicting the prognosis of CVD.

Considering that cardiovascular diseases (CVDs) are very common and can be fatal, we must have a method for assessing heart health and its probability of worsening in order to prevent and treat these diseases. In order to accomplish this, it is possible to look for biomarkers in bodily fluids that are indicative of CVD. The purpose of this article is to examine a molecule called TUG1, which is found in varying levels in patients suffering from CVD. There is an impact of TUG1 on the growth, death and inflammation response of heart cells. The potential application of TUG1 as a biomarker to predict the severity and progression of heart disease is therefore not surprising.

The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke.

Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines. Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke.

Regulatory factors involved in Th17/Treg cell balance of immune thrombocytopenia.

Immune thrombocytopenia is a common heterogeneous autoimmune disease that is characterized by decreasing peripheral blood platelet counts and increasing risk of bleeding. Studies have shown that an imbalance between T helper 17 (Th17) and Regulatory T (Treg) cells differentiated from CD4+T-cells is a key factor influencing the development and pathogenesis of immune thrombocytopenia. Th17 cells promote the development of chronic inflammatory disorders and induce autoimmune diseases, whereas Treg cells regulate immune homeostasis and prevent autoimmune diseases. Several regulators affecting the production and maintenance of these cells are also essential for proper regulation of Th17/Treg balance; these regulatory factors include cell surface proteins, miRNAs, and cytokine signaling. In this review, we focus on the function and role of balance between Th17 and Treg cells in immune thrombocytopenia, the regulatory factors, and therapeutic goals of this balance in immune thrombocytopenia.

Progranulin (PGRN) as a regulator of inflammation and a critical factor in the immunopathogenesis of cardiovascular diseases.

Immune dysregulation has been identified as a critical cause of the most common types of cardiovascular diseases (CVDs). Notably, the innate and adaptive immune responses under physiological conditions are typically regulated with high sensitivity to avoid the exacerbation of inflammation, but any dysregulation can probably be associated with CVDs. In this respect, progranulin (PGRN) serves as one of the main components of the regulation of inflammatory processes, which significantly contributes to the immunopathogenesis of such disorders. PGRN has been introduced among the secreted growth factors as one related to wound healing, inflammation, and human embryonic development, as well as a wide variety of autoimmune diseases. The relationship between the serum PGRN and TNF-α ratio with the spontaneous bacterial peritonitis constitute one of the independent predictors of these conditions. The full-length PGRN can thus effectively reduce the calcification of valve interstitial cells, and the granulin precursor (GRN), among the degradation products of PGRN, can be beneficial. Moreover, it was observed that, PGRN protects the heart against ischemia-reperfusion injury. Above all, PGRN also provides protection in the initial phase following myocardial ischemia-reperfusion injury. The protective impact of PGRN on this may be associated with the early activation of the PI3K/Akt signaling pathway. PGRN also acts as a protective factor in hyperhomocysteinemia, probably by down-regulating the wingless-related integration site Wnt/ß-catenin signaling pathway. Many studies have further demonstrated that SARS-CoV-2 (COVID-19) has dramatically increased the risks of CVDs due to inflammation, so PGRN has drawn much more attention among scholars. Lysosomes play a pivotal role in the inflammation process, and PGRN is one of the key regulators in their functioning, which contributes to the immunomodulatory mechanism in the pathogenesis of CVDs. Therefore, investigation of PGRN actions can help find new prospects in the treatment of CVDs. This review aims to summarize the role of PGRN in the immunopathogenesis of CVD, with an emphasis on its treatment.

Long non-coding RNA signatures and related signaling pathway in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy caused by clonal proliferation of T-cell pre-cursors arising from the thymus. Although the optimized chemotherapy regimen could improve the outcome of such patients, some challenges such as higher risk for induction failure, early relapse and isolated central nervous system (CNS) relapse occurring in T-ALL patients are of great significance, leading to increased mortality rates. Long non-coding RNA (lncRNA) is a key component involved in cell signaling through a variety of mechanisms in regulating gene expression. Oncogenes and tumor suppressors are no exception and their expression can be affected by lncRNAs. In addition, accumulating researches in samples from T-ALL patients as well as pre-clinical studies in mice suggest that the expression profile of lncRNAs in T-ALL could be aberrant, resulting in deregulation of target genes and downstream signaling pathways. In addition, accumulating researches in samples from T-ALL patients as well as pre-clinical studies in mice suggest that the expression profile of lncRNAs in T-ALL could be aberrant, resulting in deregulation of target genes and downstream signaling pathways. These lncRNAs may be determinants of proliferation, apoptosis, and drug resistance observed in T-ALL. Thus, lncRNAs can be a good tool to develop novel strategies against cancer cells in the treatment of relapsed and refractory T-ALL. They can also act as promoting biomarkers in assessing T-ALL and differentiating between patients with poor prognosis and good prognosis.

Omega-3 fatty acids in the treatment of spinal cord injury: untapped potential for therapeutic intervention?

Omega-3 fatty acids constitute a group of fatty acids with anti-inflammatory and preventive effects against various diseases. Studies in animal models have demonstrated the preventive and therapeutic effects of omega-3 fatty acids after spinal cord injury (SCI) in reducing inflammatory reactions and promoting neuroregeneration. However, studies on the efficacy of omega-3 fatty acids in treatment and prevention after SCI seem to be questionable. This study evaluates potential reasons for omega-3 fatty acid therapy oversight in populations after SCI. Therefore, some of the reasons could cover heterogeneous patient groups in size, level of injury, quality of life assessment, time since injury, no single standardised dose, various follow-up durations and metabolic changes, often insufficient to record. Due to the difficulty of collecting cases for the study, especially in the acute phase after SCI, multicenter, coordinated studies are needed to establish the effects of omega-3 fatty acids on treatment, recovery, and disease prevention in patients after SCI. Although the present results of such studies are still inconclusive, the failure to exploit the potential properties of omega-3 fatty acids in the treatment of patients with SCI solely due to methodological difficulties should be considered a potential waste.

Association of human papillomavirus with breast cancer: a new perspective on an old debate.

Breast cancer is a common cancer in the female population. Despite remarkable progress in the treatment of this cancer, its exact etiology is still unknown. Since the first evidence of an association between breast cancer and human papillomavirus (HPV) was provided in 1992, numerous studies have explored this subject but have reached contradictory results. In this review, the authors examine the existing evidence and hypotheses regarding the pathways whereby HPV infection can reach breast cells and the mediators linking HPV oncoproteins to breast cancer pathogenesis. Furthermore, the authors discuss contradictory findings regarding the association of HPV with breast cancer. Showing the link between HPV infection and increased genomic instability, reduced apoptosis, immune system dysfunction and progression of metastasis, the reviewed findings highlight the importance of active presence or history of HPV infection as a prognostic factor for breast tumor development.

Breast cancer is a common cancer in the female population. Although the exact cause of this cancer is still unknown, it has several major risk factors including family history, hormonal problems and age. It has been suggested that various viral infections, including human papillomavirus, can increase the likelihood of developing breast cancer. This review discusses the evidence regarding the association of human papillomavirus with breast cancer.

The role of inflammatory mediators in the pathogenesis of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome.

INTRODUCTION: As a recurrent disease, periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is characterized by episodes of febrile attacks and is often prominent in children under five years of age. However, the etiology of this condition has not been fully understood yet. MATERIALS AND METHODS: The search in the extensive literature of peer-reviewed articles published from the inception to December 2021 was conducted to identify the relevant studies, using the electronic databases of MEDLINE/PubMed, Embase, Scopus, the Cochrane Library, and the Web of Science. RESULTS: The analysis of complex relationships indicates that inflammatory factors, such as various cytokines and acute-phase proteins (APPs), play leading roles in the pathogenesis of this disease. Accordingly, this article summarizes the current state of knowledge to explain the mechanisms involved in inflammatory responses among patients with PFAPA syndrome and investigate its role in the pathogenesis of this disease. Moreover, the possibilities for further implementation of new therapeutic strategies are pointed out. CONCLUSION: It is concluded that some pathophysiological processes are associated with immune dysregulation, which itself may be secondary to environmental factors, genetic background, and underlying diseases, including latent infections that multiply inflammatory mediators. elevated inflammatory markers similarly play a significant part in the clinical outcomes of this condition, whose pyrogenic nature is the reason for the development of episodes of febrile attacks in the population of patients suffering from PFAPA syndrome.

Involvement of progranulin (PGRN) in the pathogenesis and prognosis of breast cancer.

Breast cancer constitute a common type of oncological disease with a highlighted mortality rate. In recent years, researchers have introduced progranulin (PGRN) as an novel potential biomarker and associated its function with higher risk factor for development of breast cancer. The present review article collects evidence on the association of PGRN with clinicopathological features and drug resistance in the patients with breast cancer. The results of this study suggested the use of routine determination of PGRN in the clinic as a reliable biomarker for screening people at high risk or as early indication of breast cancer. Targeting PGRN and its associated signaling pathways and receptors, such as sortilin (SORT1), could also cover a novel therapeutic strategy in the breast cancer.

CD markers polymorphisms as prognostic biomarkers in hematological malignancies.

The clusters of differentiation (CD) are surface molecules used for immunophenotyping of cells. The expression of CD markers is widely used to classify hematological malignancies, including leukemia and lymphoma. Single nucleotide polymorphisms (SNPs) are crucial genetic changes that can be associated with abnormal expression and function of CD markers. In this paper, we assess the prognostic effect of CD markers' SNPs in hematological malignancies. Materials and methods and relevant literature was identified by a PubMed search (2001-2019) of English language papers using the following terms: 'polymorphism', 'CD marker', 'leukemia', 'lymphoma', 'prognosis', 'CD marker', and 'polymorphism'. Many studies have demonstrated the effects of CD markers' polymorphisms on risk of hematological malignancies. Also, SNPs of CD markers can be related with clinicopathological features, invasiveness, and response to therapy of these disorders. Considering the importance of SNPs in the expressions of CD markers, these genetic changes could be used as potential prognostic biomarkers in hematological malignancies. It is hoped that the evaluation of SNPs in CD markers will enable early diagnosis, prognosis, and detection of response to treatment. However, better understanding of SNPs in CD markers that are involved in hematological malignancies requires further studies on different populations of the worldwide.

Prognostic significance of aberrant CD5 expression in B-cell leukemia.

Aberrant expression of CD5 (as a T-cell marker) is seen in some leukemia and lymphoma of B lineage origin. Given that the signaling resulting from the expression of this marker plays an essential role in the development of leukemia and lymphoma, evaluating the expression of this marker is of paramount importance. Therefore, our goal in this study was to investigate the prognostic importance of CD5 expression in B-cell leukemia and lymphoma. We evaluate CD5 expression in normal and leukemic B-cells by identifying relevant literature through a PubMed search (1998-2018) of English language papers using the terms: 'CD5,' 'B-cell,' 'Leukemia,' and 'Lymphoma.' We are doing this thorough comparison of results from CD5 positive and negative cases to make a correct decision about prognostic importance of CD5 expression in these malignancies. In a number of B-cell malignancies, CD5 is expressed in varying degrees. Due to the different origins and characteristics of these malignancies, the results of CD5 expression evaluations are heterogeneous and impossible to generalize. However, CD5 expression is sometimes associated with clinicopathologic findings, more invasive clinical course, and even resistance to treatment (specifically in DLBCL) among CD5- positive patients, which appears to be a function of CD5 signaling and its downstream factors such as STAT3. Depending on the type of malignancy, CD5 expression is associated with good or bad prognosis, which can be used as an auxiliary prognostic factor to assess the clinical course of B-cell malignancies. Moreover, the difference in expression levels of CD5 in a variety of B-cell malignancies allows for differential diagnosis of these malignancies, which can be helpful when diagnosis is difficult.