Tanshinone IIA Against Cerebral Ischemic Stroke and Ischemia-Reperfusion Injury: A Review of the Current Documents.

Stroke is a well-known neurological disorder that carries significant morbidity and mortality rates worldwide. Cerebral Ischemic Stroke (CIS), the most common subtype of stroke, occurs when thrombosis or emboli form elsewhere in the body and travel to the brain, leading to reduced blood perfusion. Cerebral Ischemia/Reperfusion Injury (CIRI) is a common complication of CIS and arises when blood flow is rapidly restored to the brain tissue after a period of ischemia. The therapeutic approaches currently recognized for CIS, such as thrombolysis and thrombectomy, have notable side effects that limit their clinical application. Recently, there has been growing interest among researchers in exploring the potential of herbal agents for treating various disorders and malignancies. One such herbal agent with medicinal applications is tanshinone IIA, an active diterpene quinone extracted from Salvia miltiorrhiza Bunge. Tanshinone IIA has shown several pharmacological benefits, including anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective properties. Multiple studies have indicated the protective role of tanshinone IIA in CIS and CIRI. This literature review aims to summarize the current findings regarding the molecular mechanisms through which this herbal compound improves CIS and CIRI.

RNA therapeutics for kidney injury.

RNA therapy involves utilizing RNA-based molecules to control biological pathways, aiming to cure specific diseases. As our understanding of RNA functions and their roles has expanded, the application of RNA therapies has broadened to target various therapeutic points. This approach holds promise for treating a range of diseases, including kidney diseases. Therapeutic RNA can be employed to target specific genes or pathways implicated in the development of kidney conditions, such as inflammation, fibrosis, and oxidative stress. This review highlights the therapeutic potential of RNA-based therapies across different types of kidney diseases, encompassing infection, inflammation, nephrotoxicity, and ischemia/reperfusion injury. Furthermore, studies have pinpointed the specific kidney cells involved in RNA therapy. To address challenges hindering the potential impact of RNA-based drugs on their targets, nanotechnology is integrated, and RNA-loaded vehicles with ligands are explored for more efficient outcomes.

Function of MicroRNAs in Normal and Abnormal Ovarian Activities: A Review Focus on MicroRNA-21.

Some failures in ovary function, like folliculogenesis and oogenesis, can give rise to various infertility-associated problems, including polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). PCOS influences 8 to 20% of women; while POI occurs in at least 1% of all women. Regrettably, the current therapies for these diseases have not sufficiently been effective, and finding a suitable strategy is still a puzzle. One of the helpful strategies for managing and treating these disorders is understanding the contributing pathogenesis and mechanisms. Recently, it has been declared that abnormal expression of microRNAs (miRNAs), as a subset of non-coding RNAs, is involved in the pathogenesis of reproductive diseases. Among the miRNAs, the roles of miRNA-21 in the pathogenesis of PCOS and POI have been highlighted in some documents; hence, the purpose of this mini-review was to summarize the evidences in conjunction with the functions of this miRNA and other effective microRNAs in the normal or abnormal functions of the ovary (i.e., PCOS and POI) with a mechanistic insight.

Noncoding RNAs and programmed cell death in hepatocellular carcinoma: Significant role of epigenetic modifications in prognosis, chemoresistance, and tumor recurrence rate.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high death rate in the world. The molecular mechanisms related to the pathogenesis of HCC have not been precisely defined so far. Hence, this review aimed to address the potential cross-talk between noncoding RNAs (ncRNAs) and programmed cell death in HCC. All related papers in the English language up to June 2023 were collected and screened. The searched keywords in scientific databases, including Scopus, PubMed, and Google Scholar, were HCC, ncRNAs, Epigenetic, Programmed cell death, Autophagy, Apoptosis, Ferroptosis, Chemoresistance, Tumor recurrence, Prognosis, and Prediction. According to the reports, ncRNAs, comprising long ncRNAs, microRNAs, circular RNAs, and small nucleolar RNAs can affect cell proliferation, migration, invasion, and metastasis, as well as cell death-related processes, such as autophagy, ferroptosis, necroptosis, and apoptosis in HCC by regulating cancer-associated genes and signaling pathways, for example, phosphoinositide 3-kinase/Akt, extracellular signal-regulated kinase/MAPK, and Wnt/ß-catenin signaling pathways. It seems that ncRNAs, as epigenetic regulators, can be utilized as biomarkers in diagnosis, prognosis, survival and recurrence rates prediction, chemoresistance, and evaluation of therapeutic response in HCC patients. However, more scientific evidence is suggested to be accomplished to confirm these results.

Types of RNA therapeutics.

RNA therapy is one of the new treatments using small RNA molecules to target and regulate gene expression. It involves the application of synthetic or modified RNA molecules to inhibit the expression of disease-causing genes specifically. In other words, it silences genes and suppresses the transcription process. The main theory behind RNA therapy is that RNA molecules can prevent the translation into proteins by binding to specific messenger RNA (mRNA) molecules. By targeting disease-related mRNA molecules, RNA therapy can effectively silence or reduce the development of harmful proteins. There are different types of RNA molecules used in therapy, including small interfering RNAs (siRNAs), microRNAs (miRNAs), aptamer, ribozyme, and antisense oligonucleotides (ASOs). These molecules are designed to complement specific mRNA sequences, allowing them to bind and degrade the targeted mRNA or prevent its translation into protein. Nanotechnology is also highlighted to increase the efficacy of RNA-based drugs. In this chapter, while examining various methods of RNA therapy, we discuss the advantages and challenges of each.

Does crocin create new hope for the treatment of oral problems? A focus on periodontitis.

According to the World Health Organization (WHO) reports, oral health has an indispensable role in the maintenance of human public health. However, oral problems, especially periodontitis, are known as bad players in this issue. Periodontitis, as the most prevalent oral disease, is a type of chronic illness mediated by bacterial pathogens and immune system reactions, which is linked with the destruction of tooth-protecting tissues, such as alveolar bone and periodontal ligament. Periodontitis has a high prevalence (over 40% in the United States) and can be associated with other systemic ailments, for instance, arthritis, osteoporosis, metabolic syndrome, cancer, respiratory diseases, chronic kidney disease, and Alzheimer's disease. The common treatments for periodontitis are classified into invasive (surgical) and noninvasive (antibiotic therapy, scaling, and root planning) methods; however, these therapies have not reflected enough effectiveness for related patients. New documents inform the beneficial effects of plant-based compounds in healing various disorders, like periodontitis. In conjunction with this subject, it has been revealed that crocin, as an active component of saffron, regulates the balance between osteoclasts and osteoblasts and has a stroking role in the accumulation of the most common collagen in teeth and bone (type 1 collagen). Besides, this carotenoid compound possesses anti-inflammatory and anti-oxidative effects, which can be associated with the therapeutic processes of crocin in this oral disease. Hence, this narrative review study was performed to reflect the reparative/regenerative aspects of crocin agonist periodontitis.

Mesenchymal stem cells and ovarian cancer: Is there promising news?

Ovarian cancer (OC) is described as a heterogeneous complex condition with high mortality, weak prognosis, and late-stage presentation. OC has several subgroups based on different indices, like the origin and histopathology. The current treatments against OC include surgery followed by chemotherapy and radiotherapy; however, these methods have represented diverse side effects without enough effectiveness on OC. Recently, mesenchymal stem cell (MSC)-based therapy has acquired particular attention for treating diverse problems, such as cancer. These multipotent stem cells can be obtained from different sources, such as the umbilical cord, adipose tissues, bone marrow, and placenta, and their efficacy has been investigated against OC. Hence, in this narrative review, we aimed to review and discuss the present studies about the effects of various sources of MSCs on OC with a special focus on involved mechanisms.

Breast cancer prediction using different machine learning methods applying multi factors.

OBJECTIVE: Breast cancer (BC) is a multifactorial disease and is one of the most common cancers globally. This study aimed to compare different machine learning (ML) techniques to develop a comprehensive breast cancer risk prediction model based on features of various factors. METHODS: The population sample contained 810 records (115 cancer patients and 695 healthy individuals). 45 attributes out of 85 were selected based on the opinion of experts. These selected attributes are in genetic, biochemical, biomarker, gender, demographic and pathological factors. 13 Machine learning models were trained with proposed attributes and coefficient of attributes and internal relationships were calculated. RESULT: Compared to other methods random forest (RF) has higher performance (accuracy 99.26%, precision 99%, and area under the curve (AUC) 99%). The results of assessing the impact and correlation of variables using the RF method based on PCA indicated that pathology, biomarker, biochemistry, gene, and demographic factors with a coefficient of 0.35, 0.23, 0.15, 0.14, and 0.13 respectively, affected the risk of BC (r2 = 0.54). CONCLUSION: Breast cancer has several risk factors. Medical experts use these risk factors for early diagnosis. Therefore, identifying related risk factors and their effect can increase the accuracy of diagnosis. Considering the broad features for predicting breast cancer leads to the development of a comprehensive prediction model. In this study, using RF technique a breast cancer prediction model with 99.3% accuracy was developed based on multifactorial features.

Impacts of IL-27 and IL-32 in the pathogenesis and outcome of COVID-19 associated mucormycosis.

Changes in the immune system participate in the pathogenesis and development of infectious diseases. Previous studies have indicated immune dysregulation in patients suffering from COVID-19 and mucormycosis. Therefore, this study investigated whether interleukin-27 (IL-27) and interleukin-32 (IL-32) levels may participate in the development and outcome of COVID-19 associated mucormycosis (CAM). The blood samples were obtained from 79 patients suffering from COVID-19 and mucormycosis and 25 healthy subjects. The serum samples were isolated from the whole blood and frequencies of some immune cells were measured by a cell counter. The levels of IL-27 and IL-32 were assessed by enzyme-linked immunosorbent assay. IL-27 and IL-32 levels were significantly lower in patients with COVID-19 and mucormycosis than healthy subjects (P < .05), although there was no significant difference in IL-27 between patients with COVID-19 and CAM. IL-27 level was significantly higher in severe COVID-19 survivors than dead cases (P < .01). Patients with CAM had significant increases in NLR compared to COVID-19 patients and healthy individuals (P < .0001-0.01). NLR was significantly associated with COVID-19 outcome (P < .05). Severe COVID-19 survivors had a significant reduction in NLR compared to non-survivors (P < .05). Changes in IL-27 and IL-32 levels may contribute to the pathogenesis of CAM. IL-27 may relate to the pathogenesis and outcomes of mucormycosis in COVID-19 patients.

Human umbilical cord mesenchymal stem cells: Heralding an effective treatment against esophageal cancer?

Esophageal cancer (EC), as one of the leading causes of cancer-associated mortality, influences a remarkable population of subjects globally and is histologically divided into two types, comprising esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Although several therapeutic approaches are present for EC, such as radiotherapy, chemotherapy, and surgery, these options have low success with serious side effects, for example, gastrointestinal toxicity, esophagitis, and pulmonary complications. Thus, utilizing an effective tool with low side effects is urgent. Newly, mesenchymal stem cells (MSCs) have received special interest for treating diverse diseases, such as cancer. Among different sources of MSCs, human umbilical cord MSCs have notable benefits, and reports expressed that they may be effective in EC treatment. For this purpose, in this review study, we aimed to summarize evidence regarding the effects of human umbilical cord MSCs on EC with a mechanistic insight.

Predicting roles of IL-27 and IL-32 in determining the severity and outcome of COVID-19.

OBJECTIVE: Immune changes play fundamental roles in the pathogenesis and severity of coronavirus disease 2019 (COVID-19). Previous studies have revealed alterations in immune responses of patients with non-severe and severe COVID-19. Therefore, this study investigated whether interleukin-27 (IL-27) and interleukin-32 (IL-32) levels may be considered as predicting factors for determining the severity and outcome of COVID-19. METHODS: The blood samples were collected from 50 non-severe and severe patients infected with COVID-19 and 25 healthy subjects. The serum samples were isolated from the whole blood. The levels of IL-27 and IL-32 were measured by enzyme-linked immunosorbent assay and percentages of some immune cells were studied by cell counter. RESULTS: The levels of IL-27 and IL-32 were significantly higher in COVID-19 patients than healthy subjects (p < 0.0001-0.01). IL-27 was significantly reduced in severe COVID-19 patients who needed to undergo ICU therapy (p < 0.05). Disease severity was significantly associated with IL-27 level in patients with COVID-19 (p < 0.05), unlike IL-32 level. There was a significant association between IL-27 and IL-32 in participants (p < 0.0001, odds ratio (OR) = 0.9873; 95% confidence interval (CI) = 0.9998 to 1.000; p < 0.05, OR = 0.4462; 95% CI = 0.08,579 to 0.7802; p < 0.01, OR = 0.6640, 95% CI = 0.3007-0.8590). IL-27 level was significantly higher in the recovered subjects than dead cases (p < 0.0001). IL-27 and IL-32 levels in patients who had fever were significantly higher than those who did not have (p < 0.01-0.05), unlike patients who suffered from cough (p < 0.001-0.01). The IL-27 level in patients with non-severe COVID-19 was directly correlated with CRP value (p < 0.05, OR = 0.5,722,357, 95% CI = 0.06,807,176-0.8,435,928). IL-27 and IL-32 levels in non-severe patients were positively associated with NLR (p < 0.01, OR = 0.7292; 95% CI = 0.2809 to 0.9163; p < 0.01, OR = 0.6537, 95% CI = 0.1425-0.8896). Patients with severe COVID-19 had a significant increase in NLR (p < 0.0001-0.05). NLR was significantly correlated with the disease severity (p < 0.0001-0.05). Survivors had a significant reduction in NLR compared with those who succumbed to COVID-19 (p < 0.05). CONCLUSION: Change in IL-27 level along with the frequencies of some immune cells may serve as a predictor of the severity and outcome of COVID-19.

Umbilical cord mesenchymal stem cells and breast cancer: a good therapeutic candidate or not? A minireview.

Breast cancer (BC), as the most common cancer among women, affects a great number of subjects around the world. This heterogenic disease is divided into several types and subtypes, and each subtype has various phenotypes and genotypes. Against BC, several options have been proposed, such as surgery, radiotherapy, and chemotherapeutic agents. However, these approaches may have detrimental effects on health and life quality of patients. Hence, harnessing a therapeutic tool with high effectiveness and low side effects is required. Recently, mesenchymal stem cells (MSCs) have created a new window to treat various disorders, like cancer, and among these, umbilical cord (UC)-derived MSCs have acquired much interest due to their advantages. Therefore, in this narrative review, the influences of UC-derived MSCs on BC were reviewed and summarized with a focus on the molecular mechanisms involved in its pathogenesis and treatment.

Quercetin and Osteoarthritis: A Mechanistic Review on the Present Documents.

BACKGROUND: Osteoarthritis (OA), as one of the chronic debilitating conditions, affects 15% of people globally and is linked with serious problems, such as cardiovascular diseases, metabolic syndrome, and autoimmune inflammatory disorders. The current therapeutic options for this disease include nonsteroidal anti-inflammatory drugs, surgery, gene therapy, intrasynovial gel injection, and warm needle penetration. However, these approaches may be accompanied by considerable side effects, high costs, and some limitations for patients. Thus, using an alternative way is needed. SUMMARY: Presently, natural compounds based-therapies, like flavonoids, have acquired much attention in the current era. One of the compounds belonging to the flavonoid family is quercetin, and its therapeutic effects on disorders related to joints and cartilage have been addressed in vivo and in vitro studies. KEY MESSAGES: In this review, we summarized evidence indicating its curative capacity against OA with a mechanistic insight.

Can mesenchymal stem cells derived from adipose tissue and their conditioned medium improve ovarian functions? A mini-review.

Stable ovarian function is a key factor in the performance of the reproductive system. In contrast, some ovarian function-related diseases, such as polycystic ovarian syndrome, premature ovarian failure (POF), and ovarian cancer, are the main cause of infertility and death of women around the world. Despite multiple attempts, there are no effective tools against these conditions; however, mesenchymal stem cell-based therapy, especially using adipose tissue, has attracted much attention in medicine in light of its advantages such as easy isolation and accessibility. Conversely, it has been suggested that MSC-conditioned medium (CM) can restore injured tissues and has high immunocompatibility. So, here, we will summarize the effects of administration of MSCs and CM derived from adipose tissue on ovarian functions and related diseases.

Impact of oligomerization on the allergenicity of allergens.

Type I hypersensitivity (allergic reaction) is an unsuitable or overreactive immune response to an allergen due to cross-link immunoglobulin E (IgE) antibodies bound to its high-affinity IgE receptors (FcεRIs) on effector cells. It is needless to say that at least two epitopes on allergens are required to the successful and effective cross-linking. There are some reports pointing to small proteins with only one IgE epitope could cross-link FcεRI-bound IgE through homo-oligomerization which provides two same IgE epitopes. Therefore, oligomerization of allergens plays an indisputable role in the allergenic feature and stability of allergens. In this regard, we review the signaling capacity of the B cell receptor (BCR) complex and cross-linking of FcεRI which results in the synthesis of allergen-specific IgE. This review also discusses the protein-protein interactions involved in the oligomerization of allergens and provide some explanations about the oligomerization of some well-known allergens, such as calcium-binding allergens, Alt a 1, Bet v 1, Der p 1, Per a3, and Fel d 1, along with the effects of their concentrations on dimerization.

Impacts of FcγRIIB and FcγRIIIA gene polymorphisms on systemic lupus erythematous disease activity index.

OBJECTIVE: Systemic lupus erythematous (SLE) disease is a chronic autoimmune disease with unknown etiology that can involve different organs. Polymorphisms in Fcγ receptors have been identified as genetic factors in susceptibility to SLE. This study was aimed to investigate effects of two single nucleotide polymorphisms (SNPs) within FcγRIIB and FcγRIIIA genes on systemic lupus erythematous disease activity index (SLEDAI) in an Iranian population. RESULTS: Our findings indicated TT and GG genotypes were the common genotypes of FcγRIIB and FcγRIIIA SNPs in SLE patients, respectively. There were no significant differences in genotype and allele frequencies of FcγRIIB and FcγRIIIA SNPs in SLE and healthy subjects. However, the frequencies of genotypes and alleles of FcγRIIB and FcγRIIIA SNPs were significantly associated with some clinical manifestations used to determine SLEDAI (P < 0.001-0.5).

The Therapeutic Potential of Common Herbal and Nano-Based Herbal Formulations against Ovarian Cancer: New Insight into the Current Evidence.

Ovarian cancer (OCa) is characterized as one of the common reasons for cancer-associated death in women globally. This gynecological disorder is chiefly named the "silent killer" due to lacking an association between disease manifestations in the early stages and OCa. Because of the disease recurrence and resistance to common therapies, discovering an effective therapeutic way against the disease is a challenge. According to documents, some popular herbal formulations, such as curcumin, quercetin, and resveratrol, can serve as an anti-cancer agent through different mechanisms. However, these herbal products may be accompanied by some pharmacological limitations, such as poor bioavailability, instability, and weak water solubility. On the contrary, using nano-based material, e.g., nanoparticles (NPs), micelles, liposomes, can significantly solve these limitations. Therefore, in the present study, we will summarize the anti-cancer aspects of these herbal and-nano-based herbal formulations with a focus on their mechanisms against OCa.

The expression levels of MicroRNA-146a, RANKL and OPG after non-surgical periodontal treatment.

OBJECTIVE: MicroRNA-146a (miR-146a) is a regulator of inflammatory response. Periodontitis is a disease with immune pathophysiology of the periodontium in which the inflammation results in the destruction of the soft tissues and alveolar bone. Therefore, the aim of this study was to investigate the expressions of miR-146a, OPG, and RANKL in diseased and healthy periodontal tissues to understand whether miR-146a expression level may associate with OPG and RANKL mRNA levels and OPG/RANKL ratio after non-surgical periodontal treatment. METHODS: The levels of miR-146a, RANKL, and OPG in gingival tissues from patients with generalized periodontitis stages II and III and grades A and B (n = 15, group A), patients with generalized periodontitis stages III and IV and grade C (n = 15, group B), and healthy individuals (n = 10) were determined by real-time PCR. The associations of miR-146a expression with OPG and RANKL levels were evaluated. RESULTS: The levels of miR-146a in two subgroups within periodontitis patients were significantly higher than healthy subjects (P < 0.0001). MiR-146a showed the increased level in group A of patients compared with group B (P < 0.05). Clinical parameters such as probing depth (PD) and clinical attachment loss (CAL) were significantly higher in patients than control group (P < 0.05). The levels of OPG and RANKL were increased in patients compared with healthy subjects, although the elevated levels were not statistically significant. MiR-146a was not associated with OPG and RANKL levels and OPG/RANKL ratio. CONCLUSIONS: The results of this study failed to show the associations of miR-146a level with OPG and RANKL levels and OPG/RANKL ratio in periodontitis after non-surgical periodontal treatment.

Therapeutic Aspects of Mesenchymal Stem Cell-Based Cell Therapy with a Focus on Human Amniotic Epithelial Cells in Multiple Sclerosis: A Mechanistic Review.

Multiple sclerosis (MS) is an inflammatory disease of central nervous system (CNS). The mmune system plays an important role in its pathogenesis. Current treatments are unable to cure patients and prevent the progression of MS lesions. Stem cell-based cell therapy has opened a new window for MS treatment. Stem cells regulate immune responses and improve axonal remyelination. Stem cells can be obtained from different origins such as embryonic, neural, bone marrow, and adipose tissues. But yet there is a challenge for the selection of the best cell source for stem cell therapy. Mesenchymal stem cells (MSCs) are a type of stem cell obtained from different origins and have significant immunomodulatory effects on the immune system. The increasing evidence have suggested that umbilical cord and adipose tissue can be a suitable source for isolation of MSCs. Moreover, human amniotic epithelial cells (hAECs) as novel stem cell origins by having immunoregulatory effects, regenerative effects, and less capacity of antigenicity can be a candidate for MS treatment. This review discussed the mechanistic effects of MSCs with a focus on human amniotic epithelial cells, which can be used to treatment and improvement of outcome in MS disease.