An integrated bioinformatic analysis of microarray datasets to identify biomarkers and miRNA-based regulatory networks in leishmaniasis.

Micro RNAs (miRNAs, miRs) and relevant networks might exert crucial functions during differential host cell infection by the different Leishmania species. Thus, a bioinformatic analysis of microarray datasets was developed to identify pivotal shared biomarkers and miRNA-based regulatory networks for Leishmaniasis. A transcriptomic analysis by employing a comprehensive set of gene expression profiling microarrays was conducted to identify the key genes and miRNAs relevant for Leishmania spp. infections. Accordingly, the gene expression profiles of healthy human controls were compared with those of individuals infected with Leishmania mexicana, L. major, L. donovani, and L. braziliensis. The enrichment analysis for datasets was conducted by utilizing EnrichR database, and Protein-Protein Interaction (PPI) network to identify the hub genes. The prognostic value of hub genes was assessed by using receiver operating characteristic (ROC) curves. Finally, the miRNAs that interact with the hub genes were identified using miRTarBase, miRWalk, TargetScan, and miRNet. Differentially expressed genes were identified between the groups compared in this study. These genes were significantly enriched in inflammatory responses, cytokine-mediated signaling pathways and granulocyte and neutrophil chemotaxis responses. The identification of hub genes of recruited datasets suggested that TNF, SOCS3, JUN, TNFAIP3, and CXCL9 may serve as potential infection biomarkers and could deserve value as prognostic biomarkers for leishmaniasis. Additionally, inferred data from miRWalk revealed a significant degree of interaction of a number of miRNAs (hsa-miR-8085, hsa-miR-4673, hsa-miR-4743-3p, hsa-miR-892c-3p, hsa-miR-4644, hsa-miR-671-5p, hsa-miR-7106-5p, hsa-miR-4267, hsa-miR-5196-5p, and hsa-miR-4252) with the majority of the hub genes, suggesting such miRNAs play a crucial role afterwards parasite infection. The hub genes and hub miRNAs identified in this study could be potentially suggested as therapeutic targets or biomarkers for the management of leishmaniasis.

Designing a Secretory form of RTX-A as an Anticancer Toxin: An In Silico Approach.

BACKGROUND: Cancer is a leading cause of death and a significant public health issue worldwide. Standard treatment methods such as chemotherapy, radiotherapy, and surgery are only sometimes effective. Therefore, new therapeutic approaches are needed for cancer treatment. Sea anemone actinoporins are pore-forming toxins (PFTs) with membranolytic activities. RTX-A is a type of PFT that interacts with membrane phospholipids, resulting in pore formation. The synthesis of recombinant proteins in a secretory form has several advantages, including protein solubility and easy purification. In this study, we aimed to discover suitable signal peptides for producing RTX-A in Bacillus subtilis in a secretory form. METHODS: Signal peptides were selected from the Signal Peptide Web Server. The probability and secretion pathways of the selected signal peptides were evaluated using the SignalP server. ProtParam and Protein-sol were used to predict the physico-chemical properties and solubility. AlgPred was used to predict the allergenicity of RTX-A linked to suitable signal peptides. Non-allergenic, stable, and soluble signal peptides fused to proteins were chosen, and their secondary and tertiary structures were predicted using GOR IV and I-TASSER, respectively. The PROCHECK server performed the validation of 3D structures. RESULTS: According to bioinformatics analysis, the fusion forms of OSMY_ECOLI and MALE_ECOLI linked to RTX-A were identified as suitable signal peptides. The final proteins with signal peptides were stable, soluble, and non-allergenic for the human body. Moreover, they had appropriate secondary and tertiary structures. CONCLUSION: The signal above peptides appears ideal for rationalizing secretory and soluble RTX-A. Therefore, the signal peptides found in this study should be further investigated through experimental researches and patents.

MicroRNAs and proteolytic cleavage of receptors in cancers: A comprehensive review of regulatory interactions and therapeutic implications.

Cancer remains a challenging disease worldwide, necessitating innovative approaches to better comprehend its underlying molecular mechanisms and devise effective therapeutic strategies. Over the past decade, microRNAs (miRNAs) have emerged as crucial players in cancer progression due to their regulatory roles in various cellular processes. Moreover, the involvement of unwanted soluble receptors has gained increasing attention because they contribute to tumorigenesis or drug resistance by disrupting normal signaling pathways and neutralizing ligands. This comprehensive review explores the intricate interplay between miRNAs and unwanted-soluble receptors in the context of cancer biology. This study provides an analysis of the regulatory interactions between miRNAs and these receptors, elucidating how miRNAs can either suppress or enhance their expression. MiRNAs can directly target receptor transcripts, thereby regulating soluble receptor levels. They also modulate the proteolytic cleavage of membrane-bound receptors into soluble forms by targeting sheddases, such as ADAMs and MMPs. Furthermore, the review delves into the therapeutic potential of manipulating miRNAs to modulate unwanted soluble receptors. Various strategies, including synthetic miRNA mimics or anti-miRNAs, hold promise for restoring or inhibiting miRNA function to counteract aberrant receptor activity. Moreover, exploring miRNA-based delivery systems may provide targeted and precise therapies that minimizing off-target effects. In conclusion, this review sheds light on the intricate regulatory networks involving miRNAs and unwanted soluble receptors in cancer biology thereby uncovering novel therapeutic targets, and paving the way for developing innovative anti-cancer therapies.

Optimization of Spore Production in Bacillus coagulans Using Response Surface Methodology Approach.

Due to its spore-forming ability, Bacillus coagulans has advantages over the other non-spore-forming probiotics. Among them, survival and stability during food processing and storage, resistance to acid pH, and digestive enzymes are important. However, there are few studies on the quality and amount of sporulation in B. coagulans. This study investigated the spore densities and formation efficiency of B. coagulans. The optimal medium formulation consisted of yeast extract (1.00 g L-1), potassium acetate (20.00 g L-1), and MnSO4 (0.01 g L-1 and 0.03 g L-1). After reaching the optimal medium, a response surface regression equation was established based on the results of central composite design (CCD) experimental designs to optimize time, temperature, and pH parameters. The predicted results thus obtained were in good agreement (R2 = 95.19%) with the results obtained by performing experiments. Multiple regression analysis and analysis of variance (ANOVA) showed that pH is negative, and temperature and time dose are positive factors. The maximum spore cell densities by optimization plots have obtained 9.80 log at temperature 83.77 °C, pH 3.05, and time 111.19 h, considering that B. coagulans needs special environmental and cellular conditions to enter the sporulation stage. In this study, the composition of the culture medium and factors such as temperature, time, and pH were considered influencing factors in B. coagulans sporulation.

Targeting Efficient Features of Urate Oxidase to Increase Its Solubility.

With the demand for mass production of protein drugs, solubility has become a serious issue. Extrinsic and intrinsic factors both affect this property. A homotetrameric cofactor-free urate oxidase (UOX) is not sufficiently soluble. To engineer UOX for optimum solubility, it is important to identify the most effective factor that influences solubility. The most effective feature to target for protein engineering was determined by measuring various solubility-related factors of UOX. A large library of homologous sequences was obtained from the databases. The data was reduced to six enzymes from different organisms. On the basis of various sequence- and structure-derived elements, the most and the least soluble enzymes were defined. To determine the best protein engineering target for modification, features of the most and least soluble enzymes were compared. Metabacillus fastidiosus UOX was the most soluble enzyme, while Agrobacterium globiformis UOX was the least soluble. According to the comparison-constant method, positive surface patches caused by arginine residue distribution are appropriate targets for modification. Two Arg to Ala mutations were introduced to the least soluble enzyme to test this hypothesis. These mutations significantly enhanced the mutant's solubility. While different algorithms produced conflicting results, it was difficult to determine which proteins were most and least soluble. Solubility prediction requires multiple algorithms based on these controversies. Protein surfaces should be investigated regionally rather than globally, and both sequence and structural data should be considered. Several other biotechnological products could be engineered using the data reduction and comparison-constant methods used in this study.

Escherichia coli cytosine deaminase: Structural and biotechnological aspects.

Suicide gene therapy involves introducing viral or bacterial genes into tumor cells, which enables the conversion of a nontoxic prodrug into a toxic-lethal drug. The application of the bacterial cytosine deaminase (bCD)/5-fluorocytosine (5-FC) approach has been beneficial and progressive within the current field of cancer therapy because of the enhanced bystander effect. The basis of this method is the preferential deamination of 5-FC to 5-fluorouracil by cancer cells expressing cytosine deaminase (CD), which strongly inhibits DNA synthesis and RNA function, effectively targeting tumor cells. However, the poor binding affinity of toward 5-FC compared to the natural substrate cytosine and/or inappropriate thermostability limits the clinical applications of this gene therapy approach. Nowadays, many genetic engineering studies have been carried out to solve and improve the activity of this enzyme. In the current review, we intend to discuss the biotechnological aspects of Escherichia coli CD, including its structure, functions, molecular cloning, and protein engineering. We will also explore its relevance in cancer clinical trials. By examining these aspects, we hope to provide a thorough understanding of E. coli CD and its potential applications in cancer therapy.

Magnetic hydrogel applications in articular cartilage tissue engineering.

Articular cartilage defects afflict millions of individuals worldwide, presenting a significant challenge due to the tissue's limited self-repair capability and anisotropic nature. Hydrogel-based biomaterials have emerged as promising candidates for scaffold production in artificial cartilage construction, owing to their water-rich composition, biocompatibility, and tunable properties. Nevertheless, conventional hydrogels typically lack the anisotropic structure inherent to natural cartilage, impeding their clinical and preclinical applications. Recent advancements in tissue engineering (TE) have introduced magnetically responsive hydrogels, a type of intelligent hydrogel that can be remotely controlled using an external magnetic field. These innovative materials offer a means to create the desired anisotropic architecture required for successful cartilage TE. In this review, we first explore conventional techniques employed for cartilage repair and subsequently delve into recent breakthroughs in the application and utilization of magnetic hydrogels across various aspects of articular cartilage TE.

Non-apoptotic cell death programs in cervical cancer with an emphasis on ferroptosis.

BACKGROUND: Cervical cancer, a pernicious gynecological malignancy, causes the mortality of hundreds of thousands of females worldwide. Despite a considerable decline in mortality, the surging incidence rate among younger women has raised serious concerns. Immortality is the most important characteristic of tumor cells, hence the carcinogenesis of cervical cancer cells pivotally requires compromising with cell death mechanisms. METHODS: The current study comprehensively reviewed the mechanisms of non-apoptotic cell death programs to provide possible disease management strategies. RESULTS: Comprehensive evidence has stated that focusing on necroptosis, pyroptosis, and autophagy for disease management is associated with significant limitations such as insufficient understanding, contradictory functions, dependence on disease stage, and complexity of intracellular pathways. However, ferroptosis represents a predictable role in cervix carcinogenesis, and ferroptosis-related genes demonstrate a remarkable correlation with patient survival and clinical outcomes. CONCLUSION: Ferroptosis may be an appropriate option for disease management strategies from predicting prognosis to treatment.

The Role of Tissue Factor In Signaling Pathways of Pathological Conditions and Angiogenesis.

Tissue factor (TF) is an integral transmembrane protein associated with the extrinsic coagulation pathway. TF gene expression is regulated in response to inflammatory cytokines, bacterial lipopolysaccharides, and mechanical injuries. TF activity may be affected by phosphorylation of its cytoplasmic domain and alternative splicing. TF acts as the primary initiator of physiological hemostasis, which prevents local bleeding at the injury site. However, aberrant expression of TF, accompanied by the severity of diseases and infections under various pathological conditions, triggers multiple signaling pathways that support thrombosis, angiogenesis, inflammation, and metastasis. Protease-activated receptors (PARs) are central in the downstream signaling pathways of TF. In this study, we have reviewed the TF signaling pathways in different pathological conditions, such as wound injury, asthma, cardiovascular diseases (CVDs), viral infections, cancer and pathological angiogenesis. Angiogenic activities of TF are critical in the repair of wound injuries and aggressive behavior of tumors, which are mainly performed by the actions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF1-α). Pro-inflammatory effects of TF have been reported in asthma, CVDs and viral infections, including COVID-19, which result in tissue hypertrophy, inflammation, and thrombosis. TF-FVII induces angiogenesis via clotting-dependent and -independent mechanisms. Clottingdependent angiogenesis is induced via the generation of thrombin and cross-linked fibrin network, which facilitate vessel infiltration and also act as a reservoir for endothelial cells (ECs) growth factors. Expression of TF in tumor cells and ECs triggers clotting-independent angiogenesis through induction of VEGF, urokinase-type plasminogen activator (uPAR), early growth response 1 (EGR1), IL8, and cysteine-rich angiogenic inducer 61 (Cyr61).

LYZ2-SH3b as a novel and efficient enzybiotic against methicillin-resistant Staphylococcus aureus.

BACKGROUND: Enzybiotics are promising alternatives to conventional antibiotics for drug-resistant infections. Exolysins, as a class of enzybiotics, show antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA). This study evaluated a novel exolysin containing an SH3b domain for its antibacterial activity against MRSA. METHODS: This study designed a chimeric exolysin by fusing the Cell-binding domain (SH3b) from Lysostaphin with the lytic domain (LYZ2) from the gp61 enzyme. Subsequently, LYZ2-SH3b was cloned and expressed in Escherichia coli (E. coli). Finally, the antibacterial effects of LYZ2-SH3b compared with LYZ2 and vancomycin against reference and clinical isolates of MRSA were measured using the disc diffusion method, the minimal inhibitory concentration (MIC), and the minimal bactericidal concentration (MBC) assays. RESULTS: Analysis of bioinformatics showed that LYZ2-SH3b was stable, soluble, and non-allergenic. Protein purification was performed with a 0.8 mg/ml yield for LYZ2-SH3b. The plate lysis assay results indicated that, at the same concentrations, LYZ2-SH3b has a more inhibitory effect than LYZ2. The MICs of LYZ2 were 4 µg/mL (ATCC 43,300) and 8 µg/mL (clinical isolate ST239), whereas, for LYZ2-SH3b, they were 2 µg/mL (ATCC 43,300) and 4 µg/mL (clinical isolate ST239). This suggests a higher efficiency of LYZ2-SH3b compared to LYZ2. Furthermore, the MBCs of LYZ2 were 4 µg/mL (ATCC 43,300) and 8 µg/mL (clinical isolate ST239), whereas, for LYZ2-SH3b, they were 2 µg/mL (ATCC 43,300) and 4 µg/mL (clinical isolate ST239), thus confirming the superior lytic activity of LYZ2-SH3b over LYZ2. CONCLUSIONS: The study suggests that phage endolysins, such as LYZ2-SH3b, may represent a promising new approach to treating MRSA infections, particularly in cases where antibiotic resistance is a concern. But further studies are needed.

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.

Identification of potential RapJ hits as sporulation pathway inducer candidates in Bacillus coagulans via structure-based virtual screening and molecular dynamics simulation studies.

BACKGROUND: The bacterium Bacillus coagulans has attracted interest because of its ability to produce spores and advantageous probiotic traits, such as facilitating food digestion in the intestine, managing some disorders, and controlling the symbiotic microbiota. Spore-forming probiotic bacteria are especially important in the probiotic industry compared to non-spore-forming bacteria due to their stability during production and high resistance to adverse factors such as stomach acid. When spore-forming bacteria are exposed to environmental stresses, they enter the sporulation pathway to survive. This pathway is activated by the final phosphorylation of the master regulator of spore response, Spo0A, and upon achieving the phosphorylation threshold. Spo0A is indirectly inhibited by some enzymes of the aspartate response regulator phosphatase (Rap) family, such as RapJ. RapJ is one of the most important Rap enzymes in the sporogenesis pathway, which is naturally inhibited by the pentapeptides. METHODS: This study used structure-based virtual screening and molecular dynamics (MD) simulation studies to find potential RapJ hits that could induce the sporulation pathway. The crystal structures of RapJ complexed with pentapeptide clearly elucidated their interactions with the enzyme active site. RESULTS: Based on the binding compartment, through molecular docking, MD simulation, hydrogen bonds, and binding-free energy calculations, a series of novel hits against RapJ named tandutinib, infigratinib, sitravatinib, linifanib, epertinib, surufatinib, and acarbose were identified. Among these compounds, acarbose obtained the highest score, especially in terms of the number of hydrogen bonds, which plays a major role in stabilizing RapJ-ligand complexes, and also according to the occupancy percentages of hydrogen bonds, its hydrogen bonds were more stable during the simulation time. Consequently, acarbose is probably the most suitable hit for RapJ enzyme. Notably, experimental validation is crucial to confirm the effectiveness of the selected ligands.

Molecular Mechanisms and Therapeutic Potential of Resolvins in Cancer - Current Status and Perspectives.

Resolvins are specialized pro-resolving mediators derived from omega-3 fatty acids that can suppress several cancer-related molecular pathways, including important activation of transcription parameters in the tumor cells and their microenvironment, inflammatory cell infiltration, cytokines as well as chemokines. Recently, an association between resolvins and an important anti-inflammatory process in apoptotic tumor cell clearance (efferocytosis) was shown. The inflammation status or the oncogene activation increases the risk of cancer development via triggering the transcriptional agents, including nuclear factor kappa-light-chain-enhancer of activated B cells by generating the pro-inflammatory lipid molecules and infiltrating the tumor cells along with the high level of pro-inflammatory signaling. These events can cause an inflammatory microenvironment. Resolvins might decrease the leukocyte influx into the inflamed tissues. It is widely accepted that resolvins prohibit the development of debris-triggered cancer via increasing the clearance of debris, especially by macrophage phagocytosis in tumors without any side effects. Resolvins D2, D1, and E1 might suppress tumor-growing inflammation by activation of macrophages clearance of cell debris in the tumor. Resolvin D5 can assist patients with pain during treatment. However, the effects of resolvins as anti-inflammatory mediators in cancers are not completely explained. Thus, based on the most recent studies, we tried to summarize the most recent knowledge on resolvins in cancers.

Quercetin potentiates the anti-osteoporotic effects of alendronate through modulation of autophagy and apoptosis mechanisms in ovariectomy-induced bone loss rat model.

BACKGROUND: Osteoporosis is a bone disease leading to bone fracture and affects 200 million women worldwide. Autophagy and apoptosis are two fundamental mechanisms that are involved in the development of osteoporosis. In this study we aim to investigate the combined effects of quercetin and alendronate on the markers of osteoporosis, autophagy, and apoptosis in the bone of ovariectomized rats. METHODS AND RESULTS: Fifty adult female Sprague-Dawley rats were ovariectomized and treated with alendronate alone (5 µg/kg/day) or alendronate (5 µg/kg/day) in combination with quercetin (15 mg/kg/day) for 12 weeks. Then, ELISA, stereological tests, Real-time PCR analysis, and immunofluorescence assay were used to measure the markers of osteoporosis, autophagy, and apoptosis in the serum and tibia of rats. The serum osteocalcin was significantly decreased in ovariectomized rats that received quercetin and alendronate compared with alendronate only. Stereological data showed that except for osteoclasts, the total trabecular volume, bone weight, bone volume, osteocyte, and osteoblast numbers were increased in an ovariectomized group that was treated with quercetin and alendronate compared with alendronate alone. Except for Bcl2, the autophagy markers (Beclin-1 and LC3B) and Caspase-3 were significantly downregulated in ovariectomized rats that received quercetin and alendronate compared with those treated with alendronate alone. CONCLUSION: Our results show that quercetin enhances the anti-osteoporotic effects of alendronate, possibly through the regulation of autophagy and apoptosis mechanisms. These findings suggest that the combination of quercetin and alendronate could be a useful therapeutic strategy in the treatment of osteoporosis in postmenopausal women.

Clinical Utility of Soluble CD163 and its Diagnostic and Prognostic Value in a Variety of Neurological Disorders.

Nowadays, many people suffer from Neurological Diseases (NDs), particularly neurodegenerative diseases. Hence, there is an urgent need to discover new and more effective diagnostic and prognostic biomarkers as well as therapeutic strategies for the treatment of NDs. In this context, detecting biomarkers can provide helpful information on various levels of NDs. Up to now, there has been a lot of progress in recognizing these diseases, but they are not completely clear yet. NDs are associated with inflammatory conditions and there are several differences in NDs' immune biomarkers compared to normal conditions. Among these biomarkers, soluble CD163 (sCD163) levels (as a new biomarker) increase in biofluids, relating to the activation of macrophage/microglia and inflammation levels in NDs. ADAM17/TACE and ADAM10 are the responsible enzymes for producing sCD163 from macrophages. Increased shedding of CD163 is caused by inflammatory stimuli, and a function has been hypothesized for sCD163 in immunological suppression. When the body confronts an inflammation or infection, the concentration of sCD163 drives up. sCD163 is stable and can be easily quantified in the serum. In addition to its role as a biomarker, sCD163 can be a good modulator of adaptive immune suppression after stroke. sCD163, with a long half-life, has been proposed to be a surrogate for some critical markers such as Tumor Necrosis Factor-α (TNF- α). Furthermore, sCD163 production can be regulated by some regents/approaches such as zidovudine, nanotechnology, combination antiretroviral treatment, and aprepitant. Considering the importance of the issue, the critical role of sCD163 in NDs was highlighted for novel diagnostic and prognostic purposes.

Exosomal lncRNAs in gastrointestinal cancer.

Gastrointestinal cancer (GIC) remains a leading cause of morbidity and mortality worldwide. Unfortunately, these cancers are diagnosed in advanced metastatic stages due to lack of reliable biomarkers that are sufficiently specific and sensitive in early disease. There has been growing evidence that circulating exosomes can be used to diagnose cancer non-invasively with limited risks and side effects. Furthermore, exosomal long non-coding RNAs (lncRNAs) are emerging as a new class of promising biomarkers in cancer. This review provides an overview of the extraction and detection of exosomal lncRNAs with a focus on their potential role in GIC.

Review of electrochemical and optical biosensors for testosterone measurement.

Testosterone is an anabolic steroid and a major sex hormone in males. It plays vital roles, including developing the testis, penis, and prostate, increasing muscle and bone, and sperm production. In both men and women, testosterone levels should be in normal ranges. Besides, testosterone and its analogs are major global contributors to doping in sport. Due to the importance of testosterone testing, novel, accurate biosensors have been developed. This review summarizes the various methods for testosterone measurement. Also, recent optical and electrochemical approaches for the detection of testosterone and its analogs have been discussed.

Understanding the regulation of "Don't Eat-Me" signals by inflammatory signaling pathways in the tumor microenvironment for more effective therapy.

INTRODUCTION: Receptor/ligand pair immune checkpoints are inhibitors that regulate immunity as vital "Don't Find-Me" signals to the adaptive immune system, additionally, the essential goals of anti-cancer therapy. Moreover, the immune checkpoints are involved in treatment resistance in cancer therapy. The immune checkpoints as a signal from "self" and their expression on healthy cells prevent phagocytosis. Cells (e.g., senescent and/or apoptotic cells) with low immune checkpoints, such as low CD47 and/or PD-L1, are phagocytosed, which is necessary for tissue integrity and homeostasis maintenance. In other words, cancer cells induce increased CD47 expression in the tumor microenvironment (TME), avoiding their clearance by immune cells. PD-L1 and/or CD47 expression tumors have also been employed as biomarkers to guide cure prospects. Thus, targeting innate and adaptive immune checkpoints might improve the influence of the treatments on tumor cells. However, the CD47 regulation in the TME stands intricate, so much of this process has stayed a riddle. In this line, less attention has been paid to cytokines in TME. Cytokines are significant regulators of tumor immune surveillance, and they do this by controlling the actions of the immune cell. Recently, it has been suggested that different types of cytokines at TME might cooperate with others that contribute to the regulation of CD47 and/or PD-L1. MATERIALS AND METHODS: The data were searched in available databases and a Web Search engine (PubMed, Scopus, and Google Scholar) using related keywords in the title, abstract, and keywords. CONCLUSION: Given the significant role of pro/anti-inflammatory signaling in the TME, we discuss the present understanding of pro/anti-inflammatory signaling implications in "Don't Eat-Me" regulation signals, particularly CD47, in the pathophysiology of cancers and come up with innovative opinions for the clinical transformation and personalized medicine.

The Regulation, Functions, and Signaling of miR-153 in Neurological Disorders, and Its Potential as a Biomarker and Therapeutic Target.

Treatment of neurological disorders has always been one of the challenges facing scientists due to poor prognosis and symptom overlap, as well as the progress of the disease process. Neurological disorders such as Huntington's, Parkinson's, Alzheimer's diseases, and Amyotrophic Lateral Sclerosis are very debilitating. Therefore, finding a biomarker is essential for early diagnosis and treatment goals. Recent studies have focused more on molecular factors and gene manipulation to find effective diagnostic and therapeutic biomarkers. Among these factors, microRNAs (miRNAs/ miRs) have attracted much attention. On the other hand, a growing correlation between miRNAs and neurological disorders has caused scientists to consider it as a diagnostic and therapeutic target. In this line, the miR-153 is one of the most important and highly conserved miRNAs in mice and humans, whose expression level is not only altered in neurological disorders but also improves neurogenesis. MiR-153 can regulate multiple biological processes by targeting various factors. Furthermore, the miR-153 expression also can be regulated by important regulators, such as long non-coding RNAs (e.g., KCNQ1OT1) and some compounds (e.g., Tanshinone IIA) altering the expression of miR-153. Given the growing interest in miR-153 as a biomarker and therapeutic target for neurological diseases as well as the lack of comprehensive investigation of miR-153 function in these disorders, it is necessary to identify the downstream and upstream targets and also it's potential as a therapeutic biomarker target. In this review, we will discuss the critical role of miR-153 in neurological disorders for novel diagnostic and prognostic purposes and its role in multi-drug resistance.