Exosomal microRNAs and long noncoding RNAs: as novel biomarkers for endometriosis.

Endometriosis is a gynecological inflammatory disorder characterized by the development of endometrial-like cells outside the uterine cavity. This disease is associated with a wide range of clinical presentations, such as debilitating pelvic pain and infertility issues. Endometriosis diagnosis is not easily discovered by ultrasound or clinical examination. Indeed, difficulties in noninvasive endometriosis diagnosis delay the confirmation and management of the disorder, increase symptoms, and place a significant medical and financial burden on patients. So, identifying specific and sensitive biomarkers for this disease should therefore be a top goal. Exosomes are extracellular vesicles secreted by most cell types. They transport between cells' bioactive molecules such as noncoding RNAs and proteins. MicroRNAs and long noncoding RNAs which are key molecules transferred by exosomes have recently been identified to have a significant role in endometriosis by modulating different proteins and their related genes. As a result, the current review focuses on exosomal micro-and-long noncoding RNAs that are involved in endometriosis disease. Furthermore, major molecular mechanisms linking corresponding RNA molecules to endometriosis development will be briefly discussed to better clarify the potential functions of exosomal noncoding RNAs in the therapy and diagnosis of endometriosis.

Cell membrane biomimetic nanoparticles in drug delivery.

Despite the efficiency of nanoparticle (NP) therapy, in vivo investigations have shown that it does not perform as well as in vitro. In this case, NP confronts many defensive hurdles once they enter the body. The delivery of NP to sick tissue is inhibited by these immune-mediated clearance mechanisms. Hence, using a cell membrane to hide NP for active distribution offers up a new path for focused treatment. These NPs are better able to reach the disease's target location, leading to enhanced therapeutic efficacy. In this emerging class of drug delivery vehicles, the inherent relation between the NPs and the biological components obtained from the human body was utilized, which mimic the properties and activities of native cells. This new technology has shown the viability of using biomimicry to evade immune system-provided biological barriers, with an emphasis on restricting clearance from the body before reaching its intended target. Furthermore, by providing signaling cues and transplanted biological components that favorably change the intrinsic immune response at the disease site, the NPs would be capable interacting with immune cells regarding the biomimetic method. Thus, we aimed to provide a current landscape and future trends of biomimetic NPs in drug delivery.

The role of efferocytosis and transplant rejection: Strategies in promoting transplantation tolerance using apoptotic cell therapy and/or synthetic particles.

Recently, efforts have been made to recognize the precise reason(s) for transplant failure and the process of rejection utilizing the molecular signature. Most transplant recipients do not appreciate the unknown length of survival of allogeneic grafts with the existing standard of care. Two noteworthy immunological pathways occur during allogeneic transplant rejection. A nonspecific innate immune response predominates in the early stages of the immune reaction, and allogeneic antigens initiate a donor-specific adaptive reaction. Though the adaptive response is the major cause of allograft rejection, earlier pro-inflammatory responses that are part of the innate immune response are also regarded as significant in graft loss. The onset of the innate and adaptive immune response causes chronic and acute transplant rejection. Currently employed immunosuppressive medications have shown little or no influence on chronic rejection and, as a result, on overall long-term transplant survival. Furthermore, long-term pharmaceutical immunosuppression is associated with side effects, toxicity, and an increased risk of developing diseases, both infectious and metabolic. As a result, there is a need for the development of innovative donor-specific immunosuppressive medications to regulate the allorecognition pathways that induce graft loss and to reduce the side effects of immunosuppression. Efferocytosis is an immunomodulatory mechanism with fast and efficient clearance of apoptotic cells (ACs). As such, AC therapy strategies have been suggested to limit transplant-related sequelae. Efferocytosis-based medicines/treatments can also decrease the use of immunosuppressive drugs and have no detrimental side effects. Thus, this review aims to investigate the impact of efferocytosis on transplant rejection/tolerance and identify approaches using AC clearance to increase transplant viability.

Macrophage efferocytosis in health and disease.

Creating cellular homeostasis within a defined tissue typically relates to the processes of apoptosis and efferocytosis. A great example here is cell debris that must be removed to prevent unwanted inflammatory responses and then reduce autoimmunity. In view of that, defective efferocytosis is often assumed to be responsible for the improper clearance of apoptotic cells (ACs). This predicament triggers off inflammation and even results in disease development. Any disruption of phagocytic receptors, molecules as bridging groups, or signaling routes can also inhibit macrophage efferocytosis and lead to the impaired clearance of the apoptotic body. In this line, macrophages as professional phagocytic cells take the lead in the efferocytosis process. As well, insufficiency in macrophage efferocytosis facilitates the spread of a wide variety of diseases, including neurodegenerative diseases, kidney problems, types of cancer, asthma, and the like. Establishing the functions of macrophages in this respect can be thus useful in the treatment of many diseases. Against this background, this review aimed to recapitulate the knowledge about the mechanisms related to macrophage polarization under physiological or pathological conditions, and shed light on its interaction with efferocytosis.

The cross-talk between soluble "Find me" and "Keep out" signals as an initial step in regulating efferocytosis.

The rapid clearance of apoptotic cells (ACs), known as efferocytosis, prompts the inhibition of inflammatory responses and autoimmunity and maintains homeostatic cell turnover by controlling the release of intracellular contents. The fast clearance of ACs requires professional and nonprofessional phagocytic cells that can accurately and promptly recognize ACs and migrate towards them. Cells undergoing apoptosis alarm their presence by releasing special soluble chemotactic factors, such as lactoferrin, that act as "Find me," "Keep out," or "Stay away" signals to recruit phagocytic cells, such as macrophages or prevent granulocyte migration. Efferocytosis effectively serves to prevent damage-associated molecular pattern release and secondary necrosis and inhibit inflammation/autoimmunity at the very first step. Since less attention has been given to the cross-talk and balance of "Find me" and "Keep out" signals released from ACs in efferocytosis, we set out to investigate the current knowledge of the roles of "Find me" and "Keep out" signals in the efferocytosis process.

Potential diagnostic and prognostic of efferocytosis-related unwanted soluble receptors/ligands as new non-invasive biomarkers in disorders: a review.

Efferocytosis is the process by which apoptotic cells are removed without inflammation to maintain tissue homeostasis, prevent unwanted inflammatory responses, and inhibit autoimmune responses. Coordination of efferocytosis occurs via many surfaces and chemotactic molecules and adaptors. Recently, soluble positive or negative mediators of efferocytosis, have been more noticeable as non-invasive valuable biomarkers in prognosis and targeted therapy. These soluble factors can be detected in different bodily fluids, such as serum, plasma, and urine as a non-invasive method. There are lots of studies that have tried to show the importance of receptors and ligands in disorders; while a few studies tried to indicate the importance of soluble forms of receptors/ligands and their clinical aspects as a systemic compound and shedding of targets related to efferocytosis. Some of these soluble forms also can be as sensitive as specific biomarkers for certain diseases compared with routine biomarkers, such as soluble circulatory Lectin-like oxidized low-density lipoprotein receptor-1 vs. troponin T in the acute coronary syndrome. Thus, this review tried to gain more understanding about efferocytosis-related unwanted soluble receptors/ligands, their roles, the clinical significance, and potential for diagnosis, and prognosis related to different diseases.

2q35-rs13387042 variant and the risk of breast cancer: a case-control study.

BACKGROUND: Breast Cancer is the most frequent neoplasm diagnosed among women worldwide. Genetic background and lifestyle/environment play a significant role in the disease etiology. According to Genome-wide association studies, some single-nucleotide polymorphisms such as 2q35-rs13387042-(G/A) have been introduced to be associated with breast cancer risk and features. In this study, we aimed to evaluate the association between this variant and the risk of breast cancer in a cohort of Iranian women. METHODS: Demographics and clinical information were collected by interview and using patients' medical records, respectively. DNA was extracted from 506 blood samples, including 184 patients and 322 controls, and genotyping was performed using allele specific-PCR. SPSS v16 was used for statistical analysis. RESULT: Statistically significant association was observed between AA genotype and disease risk in all patients [padj = 0.048; ORadj = 2.13, 95% CI (1.01-4.50)] and also ER-positive breast cancers [padj = 0.015; ORadj = 2.12, 95% CI (1.16-3.88)]. There was no association between rs13387042 and histopathological characteristics of the disease. Furthermore, overall survival was not statistically associated with genotype and allelic models even after adjustment for stage and receptor status (p > 0.05). CONCLUSION: There is a statistically significant association between 2q35-rs13387042 and breast cancer risk. rs13387042-AA genotype might be a risk-conferring factor for breast cancer development in the Iranian population. However, further consideration is suggested to confirm its role in risk assessment and probable association with other genetic markers.

Recent findings on the role of microRNAs in genetic kidney diseases.

BACKGROUND: MicroRNAs (miRNAs) are non-coding, endogenous, single-stranded, small (21-25 nucleotides) RNAs. Various target genes at the post-transcriptional stage are modulated by miRNAs that are involved in the regulation of a variety of biological processes such as embryonic development, differentiation, proliferation, apoptosis, inflammation, and metabolic homeostasis. Abnormal miRNA expression is strongly associated with the pathogenesis of multiple common human diseases including cardiovascular diseases, cancer, hepatitis, and metabolic diseases. METHODS AND RESULTS: Various signaling pathways including transforming growth factor-ß, apoptosis, and Wnt signaling pathways have also been characterized to play an essential role in kidney diseases. Most importantly, miRNA-targeted pharmaceutical manipulation has represented a promising new therapeutic approach against kidney diseases. Furthermore, miRNAs such as miR-30e-5p, miR-98-5p, miR-30d-5p, miR-30a-5p, miR-194-5p, and miR-192-5p may be potentially employed as biomarkers for various human kidney diseases. CONCLUSIONS: A significant correlation has also been found between some miRNAs and the clinical markers of renal function like baseline estimated glomerular filtration rate (eGFR). Classification of miRNAs in different genetic renal disorders may promote discoveries in developing innovative therapeutic interventions and treatment tools. Herein, the recent advances in miRNAs associated with renal pathogenesis, emphasizing genetic kidney diseases and development, have been summarized.

Quercetin and its role in modulating endoplasmic reticulum stress: A review.

The endoplasmic reticulum (ER) is the place where proteins and lipids are biosynthesized and where transmembrane proteins are folded. Both pathological and physiological situations may disturb the function of the ER, resulting in ER stress. Under stress conditions, the cells initiate a defensive procedure known as the unfolded protein response (UPR). Cases of severe stress lead to autophagy and/or the induction of cell apoptosis. Many studies implicate ER stress as a major factor contributing to many diseases. Therefore, the modulation of ER stress pathways has become an attractive therapeutic target. Quercetin is a plant-derived metabolite belonging to the flavonoids class which presents a range of beneficial effects including anti-inflammatory, cardioprotective, anti-oxidant, anti-obesity, anti-carcinogenic, anti-atherosclerotic, anti-diabetic, anti-hypercholesterolemic, and anti-apoptotic activities. Quercetin also has anti-cancer activity, and can be used as an adjuvant to decrease resistance to cancer chemotherapy. Furthermore, the effect of quercetin can be increased with the help of nanotechnology. This review discusses the role of quercetin in the modulation of ER stress (and related diseases) and provides novel evidence for the beneficial use of quercetin in therapy.

The regulation of CD47-SIRPα signaling axis by microRNAs in combination with conventional cytotoxic drugs together with the help of nano-delivery: a choice for therapy?

CD47, a member of the immunoglobulin superfamily, is an important "Don't Eat-Me" signal in phagocytosis process [clearance of apoptotic cells] as well as a regulator of the adaptive immune response. The lower level of CD47 on the cell surface leads to the clearance of apoptotic cells. Dysregulation of CD47 plays a critical role in the development of disorders, particularly cancers. In cancers, recognition of CD47 overexpression on the surface of cancer cells by its receptor, SIRPα on the phagocytic cells, inhibits phagocytosis of cancer cells. Thus, blocking of CD47-SIRPα signaling axis might be as a promising therapeutic target, which promotes phagocytosis of cancer cells, antigen-presenting cell function as well as adaptive T cell-mediated anti-cancer immunity. In this respect, it has been reported that CD47 expression can be regulated by microRNAs (miRNAs). MiRNAs can regulate phagocytosis of macrophages apoptotic process, drug resistance, relapse of disease, radio-sensitivity, and suppress cell proliferation, migration, and invasion through post-transcriptional regulation of CD47-SIRPα signaling axis. Moreover, the regulation of CD47 expression by miRNAs and combination with conventional cytotoxic drugs together with the help of nano-delivery represent a valuable opportunity for effective cancer treatment. In this review, we review studies that evaluate the role of miRNAs in the regulation of CD47-SIRPα in disorders to achieve a novel preventive, diagnostic, and therapeutic strategy.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Also, kindly confirm the details in the metadata are correct. Confirmed.Journal standard instruction requires a structured abstract; however, none was provided. Please supply an Abstract with subsections..Not confirmed. This is a review article. According to submission guidelines: "The abstract should be presented divided into subheadings (unless it is a mini or full review article)". Kindly check and confirm whether the corresponding authors and mail ID are correctly identified. Confirmed.

The significant role of a functional polymorphism in the NF-κB1 gene in breast cancer: evidence from an Iranian cohort.

Aims: Breast cancer (BC) is one of the most common cancers among women. The influence of genetic variations on BC risk has been thus far assessed via genome-wide association studies. NF-κB has been recognized as a major player in BC progression. In this study, the association between rs28362491 and BC was evaluated in a population from northeastern Iran. Materials & methods: This study was conducted on 476 patients with BC and 524 healthy controls. The genotyping method used was an amplification-refractory mutation system. Results: The INS/DEL genotype conferred a statistically significant increased risk in patients in comparison with controls. Additionally, in the recessive model, INS/INS + INS/DEL versus DEL/DEL was statistically significant (OR = 0.34; 95% CI: 0.12-0.96; p = 0.042). Conclusion: This study found that rs28362491, as a susceptibility genetic factor, may affect BC risk in the Iranian population.

MicroRNAs in temporal lobe epilepsy: a systematic review.

OBJECTIVE: About 30% of patients with epilepsy have drug-resistant seizures. The aim of the current endeavor was to systematically review the existing evidence on the potential applications of microRNAs as biomarkers in people with difficult to treat temporal lobe epilepsy (TLE). METHODS: MEDLINE (accessed from PubMed) and Scopus from inception to March 18, 2020 were systematically searched for related published articles. In both electronic databases, the following search strategy was implemented, and these keywords (in the title/abstract) were used: "microRNA" AND "temporal lobe epilepsy." Articles written in English that were human studies in people with epilepsy were all included in this search. RESULTS: We could identify 16 articles about different aspects of microRNAs in the serum of patients with TLE. However, only three studies robustly investigated microRNAs as potential biomarkers in the diagnosis of drug-resistant TLE (microRNA-155 (upregulated), microRNA-129-2-3p (upregulated), microRNA-153 (downregulated)). One small study provided class II, and two small studies provided class III evidence. CONCLUSION: While this systematic review identified three studies that provided some evidence on the potential applications of circulating serum microRNAs as biomarkers in people with drug-resistant TLE, the evidence is not robust yet. While these findings provide a new horizon, substantial challenges remain before the roles of microRNAs as biomarkers in the diagnosis of drug-resistant TLE can be translated into clinical practice.

Age-Specific Differences in the Severity of COVID-19 Between Children and Adults: Reality and Reasons.

In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, children experience mild symptoms compared to adults. However, the precise explanations for this disparity are not clear. Thus, we attempted to identify rational explanations about age-related differences as reported in different studies. Given the incomplete data on SARS-CoV-2, some information has been gathered from other studies of earlier coronavirus or influenza outbreaks. Age-related differences in disease severity are important with regard to diagnosis, prognosis, and treatment of SARS-CoV-2 infections. In addition, these differences impact social distancing needs, since pediatric patients with mild or asymptomatic are likely to play a significant role in disease transmission.

The Effect of Cigarette Smoke Exposure on Efferocytosis in Chronic Obstructive Pulmonary Disease; Molecular Mechanisms and Treatment Opportunities.

Cigarette smoking-related inflammation, cellular stresses, and tissue destruction play a key role in lung disease, such as chronic obstructive pulmonary disease (COPD). Notably, augmented apoptosis and impaired clearance of apoptotic cells, efferocytosis, contribute to the chronic inflammatory response and tissue destruction in patients with COPD. Of note, exposure to cigarette smoke can impair alveolar macrophages efferocytosis activity, which leads to secondary necrosis formation and tissue inflammation. A better understanding of the processes behind the effect of cigarette smoke on efferocytosis concerning lung disorders can help to design more efficient treatment approaches and also delay the development of lung disease, such as COPD. To this end, we aimed to seek mechanisms underlying the impairing effect of cigarette smoke on macrophages-mediated efferocytosis in COPD. Further, available therapeutic opportunities for restoring efferocytosis activity and ameliorating respiratory tract inflammation in smokers with COPD were also discussed.

Modeling land cover change dynamic using a hybrid model approach in Qeshm Island, Southern Iran.

Multiple factors including natural and human-induced ones lead to land cover change in the landscape. Therefore, identifying the pattern of land cover change can help inform land-use management and prevent associated issues which can affect the natural resources of the landscape. The aim of this study is to assess land cover change in the Qeshm Island in southern Iran by combining the resulting outputs of multiple modeling methods, cellular automata (CA), Markov chains, and artificial neural networks (ANN) based on land cover maps for the years 1996, 2006, and 2016 that have been extracted from satellite imagery (Landsat 5, 7, and 8). In order to evaluate the accuracy of modeling, the Kappa coefficient was calculated to be 0.8. Then, land cover changes for 2025 were predicted by a hybrid model (CA-Markov-ANN). The results indicate that the classes of built-up areas, vegetation, and mangrove forests have changed more significantly from 1996 to 2016 compared with other classes. Land cover maps generated in this study showed that built-up areas have grown significantly in recent decades due to the region's growing population and development of ports, commercial, and industrial areas. Due to the climate change, the land area covering vegetation has decreased dramatically. The size of the mangrove forests has increased over the time period of the study (1996-2025). The findings of this study can inform land-use planning decisions by providing them with a comprehensive overview of land cover conditions in the future.

The clinical importance of CD4+ CD7- in human diseases.

The CD7 antigen is a member of the immunoglobulin superfamily that expresses on the surface of all thymocytes, a majority of mature T cells, and also natural killer cells. Interestingly, under physiological and different pathological conditions, the loss of CD7 antigen occurred in the subset of CD4+ memory T cells. Various functions have been proposed for CD7, including its role in the activation and intercellular adhesiveness of T cells. Several studies indicate that the number of CD4+ CD7- T cells increases in diseases such as chronic inflammation and T-cell malignancies, these being skin inflammatory lesions. Therefore, this can be useful for the diagnosis of cancer cells, especially with reference to blood origin, treatment monitoring, and establishment of new therapies. Therefore, a comprehensive review could be useful to increase our knowledge about the clinical importance of these cells in human disease.

The prognostic and therapeutic values of long noncoding RNA PANDAR in colorectal cancer.

Long noncoding RNAs (lncRNAs) consist of 200 nucleotide sequences that play essential roles in different processes, including cell proliferation, and differentiation. There is evidence showing that the dysregulation of lncRNAs promoter of CDKN1A antisense DNA damage-activated RNA (PANDAR) leads to the development and progression in several cancers including colorectal cancer, via p53-dependent manner. This suggests that these lncRNAs may be of value as prognostic indices and a therapeutic target, as a high expression of lncRNAs PANDAR is associated with poor prognosis. Furthermore, modulating lncRNAs PANDAR has been reported to induce apoptosis and inhibit the tumor growth through modulation of cell cycle and epithelial-mesenchymal transition (EMT) pathway. The aim of the current review was to provide an overview of the prognostic and therapeutic values of lncRNAs PANDAR in colorectal cancer.

Prevalence of CCR5delta32 in Northeastern Iran.

BACKGROUND: A 32-base pair deletion (∆32) in the open reading frame (ORF) of C-C motif chemokine receptor 5 (CCR5) seems to be a protective variant against immune system diseases, especially human immunodeficiency virus type 1 (HIV-1). We aimed to assess the frequency of CCR5∆32 in the healthy Iranian population. METHODS: In this study, 400 normal samples from Khorasan, northeastern Iran, were randomly selected. The frequency of CCR5∆32 carriers was investigated using PCR analysis. Allele prevalence and the fit to the Hardy-Weinberg equilibrium were analyzed. RESULTS: The prevalence of CCR5∆32 in the northeastern population of Iran was 0.016. Four hundred samples were studied, among which one with CCR5∆32/∆32 and 11 with CCR5Wild/∆32 genotype were detected. CONCLUSION: This study was the first investigation for an assessment of the prevalence of CCR5∆32 in northeastern Iran. The low prevalence of CCR5∆32 allele in the Iranian population may result in the increased susceptibility to HIV-1. In addition, this prevalence is the same as that of reported in East Asia, while is lower than that in the Europeans.

Significant association of TOX3/LOC643714 locus-rs3803662 and breast cancer risk in a cohort of Iranian population.

Genome-wide association studies normally focus on low penetrance and moderate to high-frequency single nucleotide polymorphisms (SNPs), which lead to genetic susceptibility to breast cancer. In this regard, the T allele of rs3803662 has been associated with breast cancer risk and with lower expression level of TOX3. We aimed to assess the risk of breast cancer associated with this polymorphism in an Iranian population. Using Tetra Primer ARMS PCR, rs3803662 was analyzed in a total of 943 individuals (430 cases and 513 healthy controls form North East of Iran). Allele frequencies and genotype distribution were analyzed in case and control samples to find out any association using the Chi-squared test and Logistic regression. All cases were pathologically confirmed; all controls were mainly healthy individuals. Genotype frequencies were found to be in agreement with HWE in controls and cases. TOX3-rs3803662 SNP was associated with breast cancer risk in our study (T vs. C allele contrast model: OR 1.36, 95% CI 1.12-1.64, Pvalue = 0.002; TT vs. CT + TT dominant model: OR 0.67, 95% CI 0.51-0.87, Pvalue = 0.003; TT vs. CT + CC recessive model: OR 1.54, 95% CI 1.02-2.30, Pvlue = 0.036). Moreover, after adjusting for age, BMI, history of previous cancer and also family history of cancer, all results, except for the recessive model, were remained significant. TOX3-rs3803662, may confer some degrees of risk of breast cancer in Iranian population. This finding is in line with similar results in other populations. It highlights the importance of TOX3 pathway in tumorigenesis.

A method for improving the efficiency of DNA extraction from clotted blood samples.

BACKGROUND: The efficient and rapid extraction of high-quality genomic DNA from clotted blood samples, which normally have a low yield and poor quality, is an important factor in genomic research. The objective of this study was to develop a simple and safe technique for dispersing the blood clots by the ball bearing metal shots. Normally, such clot samples may not have an acceptable yield by conventional DNA extraction methods. Also, in the present study, we have further investigated to improve salting-out DNA extraction methods. METHODS: Initially, 500 µL phosphate-buffered saline (PBS) (1×) and two ball bearing metal shots were added to each tube of the clotted blood sample and then were gently rotated in an electric laboratory rotator for 1 hour at room temperature (18-25°C). Genomic DNA was then extracted from samples using a modified salting-out method and a modified QIAamp® DNA Blood Midi Kit and was compared with QIAamp® DNA Blood Midi Kit as a control. An assessment of the concentration and quality of the extracted DNA was performed using the UV-visible spectrophotometer. The isolated DNA proved amenable to PCR amplification and gel electrophoresis. RESULTS: The yield and purity of DNA obtained by these three methods were significantly different (P < 0.001), with a higher yield in the modified salting-out method. CONCLUSIONS: Our proposed modified salting-out method is simple and efficient for the isolation of DNA from old blood clot samples. It is both easy to use and is of low cost in routine laboratory tasks.