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 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.

Late side effects of cancer treatment in childhood cancer survivors.

INTRODUCTION: Childhood cancers are usually treated with chemotherapy and radiation. Therefore, understanding the late side effects of such treatments is important to improve the quality of life in childhood cancer survivors. The present study aimed to investigate the late complications of treatments in childhood cancer survivors. METHODS: This study is a retrospective descriptive study. A total number of 93 cases were enrolled in this study. These cases had a history of childhood cancer documented in their medical records at the Shafa Hospital, Ahvaz, Iran. The age range was 5.9-21.3 years and included 62 males and 31 female patients. RESULTS: Many of the patients at this hospital with childhood cancer had experienced chemotherapy side effects as well as late effects of cancer therapy. Hypothyroidism is a late complication of therapy in thoracic cancers and head/neck tumors with relative frequencies of 23.1% and 12.5%, respectively. Scoliosis was observed in the patients undergoing the ABVD + COPP and 8/1 regimens with relative frequencies of 4% and 50%, respectively. Lower growth percentiles were also late side effects of cancer therapy. The highest relative frequency of growth retardation was observed in the <5 age group (46.7%). Restrictive lung changes had an overall relative frequency of 6.5% in male patients with all types of tumors. Sensorineural hearing loss was observed in patients with leukemia and Hodgkin lymphoma with relative frequencies of 8.7% and 24.0, respectively. CONCLUSION: The occurrence of most side effects could be decreased through early diagnosis, dose adjustment of some drugs, and preventative measures.

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.

Association between extract of Euphorbia szovitsii and expression level of microRNAs in MDA-MB-231 cell line.

BACKGROUND: The miRNAs have been shown to be involved in breast cancer. The aim of the present research was to evaluate the impacts of extract from Euphorbia szovitsii Fisch & C.A. Mey on the expression level of microRNAs in triple-negative breast cancer (MDA-MB-231) cell line. METHODS AND RESULT: The alterations in the expression level of miRNAs in MDA-MB-231 cell line exposed to the extract of E. szovitsii were determined exploiting qRT-PCR technique. The expression of MDA-MB-231 cell microRNAs including miR-15, miR-16, miR-21, miR-29, miR-34a, miR-146b, miR-151, miR-155, miR-181b, miR-221, miR-222, and Let-7 was evaluated at 24 and 48 h after treatment with the E. szovitsii extract. The treatment of MDA-MB-231 cells with E. szovitsii caused a significant elevation in the expression of miR-155, miR-146b (P < 0.05), miR-16, miR-21, miR-151 (P < 0.01), and miR-34a (P < 0.001) after 24 h, and also miR-155, Let-7 (P < 0.05), miR-15, miR-29, miR-151 (P < 0. 01), miR-146b and miR-34a (P<0.001) after 48 h. CONCLUSIONS: The qRT-PCR findings at 24 and 48 h after treatment revealed that the MDA-MB-231 cell line in the presence of E. szovitsii extract showed an alteration in the expression profile of miRNAs implicated in the induction of cell proliferation, apoptosis and migration. These results may be helpful in determining the anticancer activity of E. szovitsii in MDA-MB-231 cell line.

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.

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.

Tranilast: a potential anti-Inflammatory and NLRP3 inflammasome inhibitor drug for COVID-19.

SARS-CoV-2 is a type of beta-CoV that develops acute pneumonia, which is an inflammatory condition. A cytokine storm has been recognized as one of the leading causes of death in patients with COVID-19. ALI and ARDS along with multiple organ failure have also been presented as the consequences of acute inflammation and cytokine storm. It has been previously confirmed that SARS-CoV, as another member of the beta-CoV family, activates NLRP3 inflammasome and consequently develops acute inflammation in a variety of ways through having complex interactions with the host immune system using structural and nonstructural proteins. Numerous studies conducted on Tranilast have further demonstrated that the given drug can act as an effective anti-chemotactic factor on controlling inflammation, and thus, it can possibly help the improvement of the acute form of COVID-19 by inhibiting some key inflammation-associated transcription factors such as NF-κB and impeding NLRP3 inflammasome. Several studies have comparably revealed the direct effect of this drug on the prevention of inappropriate tissue's remodeling; inhibition of neutrophils, IL-5, and eosinophils; repression of inflammatory cell infiltration into inflammation site; restriction of factors involved in acute airway inflammation like IL-33; and suppression of cytokine IL-13, which increase mucosal secretions. Therefore, Tranilast may be considered as a potential treatment for patients with the acute form of COVID-19 along with other drugs.

Differentiation of dental pulp stem cells into neuron-like cells.

Background and objectives: With regard to their ease of harvest and common developmental origin, dental pulp stem cells (DPSCs) may act as a favorable source of stem cells in generation of nerves. Moreover; cellular migration and differentiation as well as survival, self-renewal, and proliferation of neuroprogenitor species require the presence of the central nervous system (CNS) mitogens including EGF and bFGF. Accordingly, the possibility of the induction of neuronal differentiation of DPSCs by EGF and bFGF was evaluated in the present study.Materials and methods: DPSCs were treated with 20 ng/ml EGF, 20 ng/ml bFGF, and 10 µg/ml heparin. In order to further induce the neuroprogenitor differentiation, DPSC-derived spheres were also incubated in serum-free media for three days. The resulting spheres were then cultured in high-glucose Dulbecco's Modified Eagle Medium (DMEM) with 10% FBS. The morphology of the cells and the expression of the differentiation markers were correspondingly analyzed by quantitative polymerase chain reaction (qPCR), western blotting, and immunofluorescence (IF).Results: The EGF/bFGF-treated DPSCs showed significant increase in the expression of the neuroprogenitor markers of Nestin and SRY (sex determining region Y)-box 2 (SOX2), 72 h after treatment. The up-regulation of Nestin and SOX2 induced by growth factors was confirmed using western blotting and IF. The cultures also yielded some neuron-like cells with a significant rise in Nestin, microtubule-associated protein 2 (MAP2), and Neurogenin 1 (Ngn1) transcript levels; compared with cells maintained in the control media (p < 0.05).Conclusion: DPSCs seemed to potentially differentiate into neuron-like cells under the herein-mentioned treatment conditions.

The Effect of the MicroRNA-183 Family on Hair Cell-Specific Markers of Human Bone Marrow-Derived Mesenchymal Stem Cells.

Hearing loss is considered the most common sensory disorder across the world. Nowadays, a cochlear implant can be an effective treatment for patients. Moreover, it is often believed that sensorineural hearing loss in humans is caused by loss or disruption of the function of hair cells in the cochlea. In this respect, mesenchymal cells can be a good candidate for cell-based therapeutic approaches. To this end, the potential of human bone marrow-derived mesenchymal stem cells to differentiate into hair cells with the help of transfection of microRNA in vitro was investigated. MicroRNA mimics (miRNA-96, 182, and 183) were transfected to human bone marrow-derived mesenchymal stem cells using Lipofec-tamine as a common transfection reagent following the manufacturer's instructions at 50 nM for microRNA mimics and 50 nM for the scramble. The changes in cell morphology were also observed under an inverted microscope. Then, the relative expression levels of SOX2, POU4F3, MYO7A, and calretinin were assayed using real-time polymerase chain reaction according to the ΔΔCt method. The ATOH1 level was similarly measured via real-time polymerase chain reaction and Western blotting. The results showed that increased expression of miRNA-182, but neither miRNA-96 nor miRNA-183, could lead to higher expression levels in some hair cell markers. The morphology of the cells also did not change in this respect, but the evaluation of gene expression at the levels of mRNA could promote the expression of the ATOH1, SOX2, and POU4F3 markers. Furthermore, miRNA-182 could enhance the expression of ATOH1 at the protein level. According to the results of this study, it was concluded that miRNA-182 could serve as a crucial function in hair cell differentiation by the upregulation of SOX2, POU4F3, and ATOH1 to promote a hair cell's fate.

Combined Growth Factor and Gene Therapy: An Approach for Hair Cell Regeneration and Hearing Recovery.

INTRODUCTION: Fibroblast growth factor, nerve growth factor neurotrophins, and insulin-like growth factor 1 are considered 3 families of growth factors that can be involved in the process of otic neurogenesis. In this respect, otic neurons can also be connected with mechanoreceptors in the ear, the hair cells (HCs), as well as the central nervous system. As a growth factor is combined with gene transfer technology, it can be used for hair cell regeneration. Gene therapy can be similarly employed to introduce genes into a system in order to induce the expression of genes for therapeutic agents, to replace defective genes, or to re-program supporting or surrounding cells to acquire the phenotype of lost or damaged cells in order to repair or regenerate the damaged tissue. OBJECTIVE: The purpose of this review article was to investigate the epigenetic and growth factors involved in the differentiation pathway of embryonic stem cells (ESCs) into HCs and auditory neurons (ANs). METHODS: To this end, the databases of Directory of Open Access Journals, Google Scholar, PubMed (NLM), LISTA (EBSCO), as well as Web of Science were searched. RESULTS: Given the results available in the related literature, the differentiation efficacy of ESCs toward the ANs and the HCs, the important role of growth factors, and 3 different strategies of application of miRNA, epigenetic regulation, and preparation of three-dimensional (3D) environments were suggested to be taken into consideration in order to improve these studies in the future. Furthermore, the role of epige-netic mechanisms and miRNA in this differentiation process became quite obvious; hence, the utilization of such procedures in the near future would be significant. CONCLUSION: Combining several techniques with a synergic effect (such as growth factor gene therapy and 3D environments) seemed to lead to obtaining the best results as a therapeutic strategy.

MicroRNAs: effective elements in ear-related diseases and hearing loss.

miRNAs are important factors for post-transcriptional process that controls gene expression at mRNA level. Various biological processes, including growth and differentiation, are regulated by miRNAs. miRNAs have been demonstrated to play an essential role in development and progression of hearing loss. Nowadays, miRNAs are known as critical factors involved in different physiological, biological, and pathological processes, such as gene expression, progressive sensorineural hearing loss, age-related hearing loss, noise-induced hearing loss, cholesteatoma, schwannomas, and inner ear inflammation. The miR-183 family (miR-183, miR-96 and miR-182) is expressed abundantly in some types of sensory cells in inner ear specially mechanosensory hair cells that exhibit a great expression level of this family. The plasma levels of miR-24-3p, miR-16-5p, miR-185-5p, and miR-451a were upregulated during noise exposures, and increased levels of miR-21 have been found in vestibular schwannomas and human cholesteatoma. In addition, upregulation of pro-apoptotic miRNAs and downregulation of miRNAs which promote differentiation and proliferation in age-related degeneration of the organ of Corti may potentially serve as a helpful biomarker for the early detection of age-related hearing loss. This knowledge represents miRNAs as promising diagnostic and therapeutic tools in the near future.

In Vitro Differentiation of Human Bone Marrow Mesenchymal Stem Cells to Hair Cells Using Growth Factors.

OBJECTIVE: In this study, we attempted to differentiated human bone marrow-derived mesenchymal stem cells (hBMSCs) to auditory hair cells using growth factors. METHODS: Retinoic acid (RA), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) were added to hBMSCs cell culture medium. The cells were evaluated morphologically and the expression of SOX2, POU4F3, MYO7A, and Calretinin at mRNA level and ATOH1 mRNA and protein expression. RESULTS: After treatment with the growth factors, the morphology of the cells did not change, but evaluation of gene expression at the mRNA level increased the expression of the ATOH1, SOX2, and POU4F3 markers. Growth factors increased the expression of ATOH1 at the protein level. The expression of calretinin showed decreased and MYO7A no significant change in expression. CONCLUSION: hBMSCs have the potential to differentiate to hair cell-like using the RA, bFGF, and EGF.

A Review of Medicinal Plants for the Treatment of Earache and Tinnitus in Iran.

BACKGROUND AND PURPOSE: Despite numerous trials, there has not yet been any definite strategy to reduce replicable long-term tinnitus and earache. Complementary and alternative medical approaches have been used to decrease the symptoms of tinnitus and earache. This study was conducted to report medicinal plants that are used to treat ear disorders, especially earache and tinnitus in different regions of Iran. EVIDENCE ACQUISITIONS: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, LISTA (EBSCO), Embase, and Web of Science were searched using relevant search terms to retrieve eligible publications. RESULTS: Twenty-three species from sixteen families were used for the treatment of earache and tinnitus in Iran. Plants from families Asteraceae and Lamiaceae were the most commonly used plants for the treatment of earache. Ginkgo biloba was frequently reported for the treatment of tinnitus. CONCLUSION: This study shows the important role of medicinal plants in the treatment of earache and tinnitus in some regions of Iran. The medicinal plants reported in this review can be considered in treatments for earache and tinnitus if examined more extensively in clinical trials.

Ginkgo biloba in the treatment of tinnitus: An updated literature review.

INTRODUCTION: Tinnitus is one of the common diseases of the ear that is associated with numerous physical and mental disorders. One of the known mechanisms in the tinnitus area with unknown reason is oxidative events. Based on the prevalence and economic costs and physical- psychological side effects caused by tinnitus and the importance of finding a suitable solution for its prevention and treatment, the need for further studies becomes more obvious in this context. This review article aimed to review studies on the effectiveness of Ginkgo biloba as a medicinal plant on patients with tinnitus. EVIDENCE ACQUISITIONS: Google Scholar, Directory of Open Access Journals (DOAJ), PubMed, LISTA (EBSCO) and Web of Science have been searched. RESULTS: There are many studies on the therapeutic effect of Ginkgo biloba on patients with tinnitus. Most findings are in contrast with each other so that some of studies reported that Ginkgo biloba is effective in the treatment of tinnitus and other studies referred to it as ineffective herbal medicine. Generally, according to the previous studies and the present study, it can mention that the Ginkgo biloba may somewhat improve tinnitus. CONCLUSION: Since tinnitus is multifactorial, it is recommended to evaluate patients individually based on the cause of tinnitus, treatment formulas, and different doses of Ginkgo biloba at the more extensive level in future studies.

Comparison of Three Types of Mesenchymal Stem Cells (Bone Marrow, Adipose Tissue, and Umbilical Cord-Derived) as Potential Sources for Inner Ear Regeneration.

In this review, we compared the potential of mesenchymal stem cells derived from bone marrow, adipose tissue and umbilical cord as suitable sources for regeneration of inner ear hair cells and auditory neurons. Our intensive literature search indicates that stem cells in some of adult mammalian tissues, such as bone marrow, can generate new cells under physiological and pathological conditions. Among various types of stem cells, bone marrow-derived mesenchymal stem cells are one of the most promising candidates for cell replacement therapy. Mesenchymal stem cells have been reported to invade the damaged area, contribute to the structural reorganization of the damaged cochlea and improve incomplete hearing recovery. We suggest that bone marrow-derived mesenchymal stem cells would be more beneficial than other mesenchymal stem cells.

The prognostic potential of long noncoding RNA XIST in cardiovascular diseases: a review.

There is a significant mortality rate associated with cardiovascular disease despite advances in treatment. long Non-coding RNAs (lncRNAs) play a critical role in many biological processes and their dysregulation is associated with a wide range of diseases in which their downstream pathways are disrupted. A lncRNA X-inactive specific transcript (XIST) is well known as a factor that regulates the physiological process of chromosome dosage compensation for females. According to recent studies, lncRNA XIST is involved in a variety of cellular processes, including apoptosis, proliferation, invasion, metastasis, oxidative stress and inflammation, through molecular networks with microRNAs and their downstream targets in neoplastic and non-neoplastic diseases. Because these cellular processes play a role in the pathogenesis of cardiovascular diseases, we aim to investigate the role that lncRNA XIST plays in this process. Additionally, we wish to determine whether it is a prognostic factor or a potential therapeutic target in these diseases.

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MIR96 Has Good Potential to Differentiate Human Bone Marrow-Derived Mesenchymal Stem Cells into Photoreceptor-Like Cells.

OBJECTIVES: MicroRNAs play an important role in the development and function of neuron cells. Among these, the miRNA known as MIR96 is abundantly expressed in mammalian retina and significantly affects differentiation, maturation, and survival of human photoreceptor cells. In this study, a mimic to miRNA-96 was transfected into human bone marrowderived mesenchymal stem cells to explore the biological functions of MIR96 at differentiation processing. MATERIALS AND METHODS: A mimic to miRNA-96 and a competitive control were transfected into human bone marrow-derived mesenchymal stem cells using Lipofectamine. After 24 and 48 hours, we evaluated changes in expression levels of genes associated with neural progenitor and photoreceptor differentiation (OTX2, NRL, protein kinase C, SLC1A1, and recoverin) by real-time polymerase chain reaction. In addition, we measured expression of mRNA and protein of the CRX gene (neuroretinal progenitor cell marker) and the RHO gene (terminal differentiation marker) using real-time polymerase chain reaction and immunocytochemistry, respectively. RESULTS: Real-time polymerase chain reaction results showed increased levels of RHO and recoverin mRNA after 24 hours in transfected cells. In addition, mRNA levels of OTX2, CRX, NRL, RHO, recoverin, and protein kinase C increased after 48 hours in transfected cells. Immunocytochemistry results confirmed these findings by demonstrating RHO and CRX at both 24 and 48 hours in transfected cells. CONCLUSIONS: Control of the expression of MIR96 can be a good strategy to promote cell differentiation and can be used in cell therapy for retinal degeneration. Our results showed that human bone marrow-derived mesenchymal stem cells can differentiate into photoreceptor cells after transfection with MIR96. These results support therapeutic use of MIR96 in retinal degeneration and suggest human bone marrowderived mesenchymal stem cells as a promising tool for interventions.

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 Effects of Convalescent Plasma Transfusion on Serum Levels of Macrophage-Associated Inflammatory Biomarkers in Patients with Severe COVID-19.

As an antibody-based therapy, plasma therapy has been used as an emergency therapeutic strategy against severe acute respiratory syndrome coronavirus type 2 infection. Due to the critical role of macrophages in coronavirus disease-19 (COVID-19)-associated hyperinflammation, the main objective of this study was to assess the effect of plasma transfusion on the expression levels of the inflammatory biomarkers involved in activation and pulmonary infiltration of macrophages. The target population included 50 severe hospitalized COVID-19 patients who were randomly assigned into 2 groups, including intervention and control. Serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL-3, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction (PCR) was carried out to assess the relative expression of nuclear factor (NF)-κB1, NF-κB2, nuclear factor erythroid 2 p45-related factor 2 (NRF-2), and thioredoxin-interacting protein genes. Sampling was done at baseline and 72 h after receiving plasma. The intervention group demonstrated significantly lower serum levels of IL-6, TNF-α, and CCL-3. In addition, real-time PCR data analyses showed that the relative expression of NF-κB2 was significantly declined in the patients who received plasma. The use of convalescent plasma probably has a significant inhibitory effect on the cytokines, chemokines, and inflammatory genes related to macrophage activation, which are closely associated with the worsening of clinical outcomes in severe COVID-19.