Autophagy as a self-digestion signal in human cancers: Regulation by microRNAs in affecting carcinogenesis and therapy response.

Autophagy is defined as a "self-digestion" signal, and it is a cell death mechanism its primary function is degrading toxic agents and aged organelles to ensure homeostasis in cells. The basic leve ls of autophagy are found in cells, and when its levels exceed to standard threshold, cell death induction is observed. Autophagy dysregulation in cancer has been well-documented, and regulation of this pathway by epigenetic factors, especially microRNAs (miRNAs), is interesting and noteworthy. miRNAs are considered short endogenous RNAs that do not encode functional proteins, and they are essential regulators of cell death pathways such as apoptosis, necroptosis, and autophagy. Accumulating data has revealed miRNA dysregulation (upregulation or downregulation) during tumor progression, and their therapeutic manipulation provides new insight into cancer therapy. miRNA/autophagy axis in human cancers has been investigated an exciting point is the dual function of both autophagy and miRNAs as oncogenic and onco-suppressor factors. The stimulation of pro-survival autophagy by miRNAs can increase the survival rate of tumor cells and mediates cancer metastasis via EMT inductionFurthermore, pro-death autophagy induction by miRNAs has a negative impact on the viability of tumor cells and decreases their survival rate. The miRNA/autophagy axis functions beyond regulating the growth and invasion of tumor cells, and they can also affect drug resistance and radio-resistance. These subjects are covered in the current review regarding the new updates provided by recent experiments.

In Vivo and In Vitro Biocompatibility Study of CuS Nanoparticles: Photosensitizer for Glioblastoma Photothermal Therapy.

Although photothermal treatment (PTT) has made significant progress in the fight against cancer, certain types of malignant tumors are still difficult to eradicate. PTT uses photothermal transforming agents to absorb NIR light and convert it to thermal energy, causing cancer cell death. In this study, we synthesized alginate (Alg)-coated CuS nanoparticles (CuS@Alg) as photothermal transforming agents to kill glioblastoma cancer cells. Nanoparticles were synthesized via a facile method, then, were characterized with different techniques such as ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared (FTIR), X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Nanoparticles show high stability, and are monodisperse. CuS@Alg was discovered to have a spherical shape, a hydrodynamic size of about 19.93 nm, and a zeta potential of - 9.74 mV. CuS@Alg is able to increase temperature of medium under NIR light. Importantly, in vitro investigations show that PTT based on CuS@Alg has a strong theraputic impact, resulting in much high effectiveness. The LD50 and histopathology assays were used to confirm the NPs' non-toxicity in vivo. Results from an in vivo subacute toxicity investigation showed that the fabricated NPs were perfectly safe to biomedical usage.

Implications of biomimetic nanocarriers in targeted drug delivery.

Nanomaterials and nanostructures have shown fascinating performances in various biomedicine fields, from cosmetic to cancer diagnosis and therapy. Engineered nanomaterials can encapsulate both lipophilic and hydrophilic substances/drugs to eliminate their limitations in the free forms, such as low bioavailability, multiple drug administration, off-target effects, and various side effects. Moreover, it is possible to deliver the loaded cargo to the desired site of action using engineered nanomaterials. One approach that has made nanocarriers more sophisticated is the "biomimetic" concept. In this scenario, biomolecules (e.g., natural proteins, peptides, phospholipids, cell membranes) are used as building blocks to construct nanocarriers and/or modify agents. For instance, it has been reported that specific cells tend to migrate to a particular site during specific circumstances (e.g., inflammation, tumor formation). Employing the cell membrane of these cells as a coating for nanocarriers confers practical targeting approaches. Accordingly, we introduce the biomimetic concept in the current study, review the recent studies, challenge the issues, and provide practical solutions.

Long non-coding RNAs: The modulators of innate and adaptive immune cells.

Before very sensitive current genomics platforms were discovered, long non-coding RNAs (lncRNAs) as controllers of gene expression, were thought to be accumulated genetic garbage. The past few years have seen a lot of interest in a large classification of non-coding transcripts with an indeterminate length of more than 200 nucleotides [1]. lncRNAs' association with immunity and disease progression has been revealed by a growing body of experimental research. Only a limited subset of lncRNAs, however, has solid proof of their role. It is also clear that various immune cells express lncRNAs differently. In this review, we concentrated on the role of lncRNA expression in the regulation of immune cell function and response to pathological conditions in macrophages, dendritic cells, natural killer (NK) cells, neutrophils, Myeloid-derived suppressor cells (MDSCs), T cells, and B cells. The innate and adaptive immune response systems may be significantly regulated by lncRNAs, according to emerging research. To discover possible therapeutic targets for the therapy of different diseases, it may be helpful to have a better realization of the molecular mechanisms beyond the role of lncRNAs in the immune response. Therefore, it is crucial to investigate lncRNA expression and comprehend its significance for the immune system.

Microplastic and oil pollutant agglomerates synergistically intensify toxicity in the marine fish, Asian seabass, Lates calcalifer.

Asian seabass, Lates calcarifer frys were exposed to polystyrene (MP: 0.5 mg/l), oil (0.83 ml/l) and agglomerates (MP + oil + Corexit) as eight treatments in three replicates, and fresh synthetic marine water (control) for 15 days. The synergistic effect was confirmed (P ˂ 0.05) by bio-indicators including RBC count, total plasma protein, aspartate aminotransferase (AST), catalase (CAT), glutathione S-transferase (GST), basophils, thrombocyte and eosinophils percentages. Most of the significant and synergistic effects were observed in the highest doses (5 mg/l MP and 5 mg/l MP-oil-dispersant). Exposure to MP and a combination of MP+ oil caused tissue lesions in gill, liver and intestine. Our results suggest there are no critical health issues for Asian seabass in natural environments. However, the bioaccumulation of MPs, oil, and their agglomerates in consumers' bodies may remain a concern.

MicroRNA-32 Suppression: its Effects on Prostate Cancer Cells' Capability to Proliferate and Migrate.

INTRODUCTION: This paper sought to scrutinize the role of microRNA-32 (miR-32) on the growth and migration as well as on the expression of metastatic genes in PC3 cells of prostate cancer in vitro. METHODS: Subsequent transfection of cells with miR-32 mimics, miR-32 inhibitor, negative control (NC), cell proliferation using MTT, and apoptosis by ELISA were performed. Furthermore, qRT-PCR was directed to measure the expression levels of matrix metalloproteinase 2 (MMP2) and vascular endothelial growth factors (VEGF) as metastatic and angiogenesis genes in the progression of PC3. RESULTS: miR-32 was overexpressed in PC3 cells compared to normal cells (P<0.001). Down-regulation of miR-32 obstructs in vitro proliferation and migration while intensifying the apoptosis rate in PC3 cells. Also, we found that miR-32 negatively modulates the expression of VEGF and MMP2 in PC3 cells. CONCLUSION: These results indicate that the suppression of miR-32 might offer an auxiliary treatment procedure for addressing the invasion, progression, and metastasis in PCa patients by improving cell apoptosis.

The role of endoplasmic reticulum stress in endometriosis.

Endometriosis is a chronic gynecologic disorder characterized by abnormal growth of endometrium-like tissues in the ectopic regions of the pelvic peritoneum. The pathophysiology of endometriosis is not completely understood; however, excessive endometrial cell proliferation together with resistance to apoptosis facilitates the migration, implantation, and survival of endometrial cells in the distant sites. Endoplasmic reticulum (ER) stress response (also called unfolded protein response) is a cellular defense mechanism triggered by ER stress. When severe enough, the so-called response initiates cell suicide, i.e., apoptosis. Therefore, therapeutic induction of ER stress in endometriotic cells could promote apoptosis and contribute to the management of disease. In this review, we discuss the pathogenic role of ER stress in endometriosis and the most recent findings regarding the induction of ER stress in connection with endometriosis.

Non-coding RNAs, another side of immune regulation during triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is considered about 12-24 % of all breast cancer cases. Patients experience poor overall survival, high recurrence rate, and distant metastasis compared to other breast cancer subtypes. Numerous studies have highlighted the crucial roles of non-coding RNAs (ncRNAs) in carcinogenesis and proliferation, migration, and metastasis of tumor cells in TNBC. Recent research has demonstrated that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play a role in the regulation of the immune system by affecting the tumor microenvironment, the epithelial-mesenchymal transition, the regulation of dendritic cells and myeloid-derived stem cells, and T and B cell activation and differentiation. Immune-related miRNAs and lncRNAs, which have been established as predictive markers for various cancers, are strongly linked to immune cell infiltration and could be a viable therapeutic target for TNBC. In the current review, we discuss the recent updates of ncRNAs, including miRNAs and lncRNAs in TNBC, including their biogenesis, target genes, and biological function of their targets, which are mostly involved in the immune response.

Various types of electrochemical biosensors for leukemia detection and therapeutic approaches.

Leukemia often initiates following dysfunctions in hematopoietic stem cells lineages. Various types of leukemia, including acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), acute promyelocytic leukemia (APL), and human T-cell leukemia/lymphoma virus type 1 (HTLV-1) can thus call for different diagnosis and treatment options. One of the most important subjects in leukemia is the early detection of the disease for effective therapeutic purposes. In this respect, biosensors detecting the molecules of deoxyribonucleic acid (DNA) as analytes are called genosensors or DNA biosensors. Electrochemical sensors, as the most significant approach, also involve reacting of chemical solutions with sensors to generate electrical signals proportional to analyte concentrations. Biosensors can further help detect cancer cells in the early stages of the disease. Moreover, electrochemical biosensors, developed based on various nanomaterials (NMs), can increase sensitivity to the detection of leukemia-related genes, e.g., BCR/ABL as a fusion gene and promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα). Therefore, the present review reflects on previous studies recruiting different NMs for leukemia detection.

Mesenchymal stromal/stem cells and their exosomes application in the treatment of intervertebral disc disease: A promising frontier.

Today, the application of mesenchymal stromal/stem cells (MSCs) and their exosomes to treat degenerative diseases has received attention. Due to the characteristics of these cells, such as self-renewability, differentiative and immunomodulatory effects, their use in laboratory and clinical studies shows promising results. However, the allogeneic transplantation problems of MSCs limit the use of these cells in the clinic. Scientists propose the application of exosomes to use from the therapeutic effect of MSCs and overcome their defects. These vesicles change the target cell behaviour and transcription profile by transferring various cargo such as proteins, mi-RNAs, and lipids. One of the degenerative tissue diseases in which MSCs and their exosomes are used in their treatment is intervertebral disc disease (IDD). Different factors such as genetics, nutrition, ageing, and environmental factors play a significant role in the onset and progression of this disease. These factors affect the cellular and molecular properties of the disc, leading to tissue destruction. Nucleus pulposus cells (NPCs) are among the most important cells involved in the pathogenesis of disc degeneration. MSCs exert their therapeutic effects by differentiating, reducing apoptosis, increasing proliferation, and decreasing senescence in NPCs. In addition, the use of MSCs and their exosomes also affects the annulus fibrosus and cartilaginous endplate cells in disc tissue and prevents disc degeneration progression.

Dietary Thymol Improved Growth, Body Composition, Digestive Enzyme Activities, Hematology, Immunity, Antioxidant Defense, and Resistance to Streptococcus iniae in the Rainbow Trout (Oncorhynchus mykiss).

In this study, thymol (TYM) at dietary levels of 0, 1, 1.5, 2, and 2.5 g/kg diet was used to evaluate its effects on growth, digestive performance, immunity, and resistances to the infection induced by Streptococcus iniae in the rainbow trout, Oncorhynchus mykiss. A number of 450 fish (35.8 ± 4.4 g; Mean ± SD) were distributed to 15 tanks (30 fish/tank) in three replicates and fed TYM for 60 days. After feeding period, Fish fed 1.5-2.5 g TYM showed better growth, higher digestive enzyme activity, and body protein content compared to other diets (P < 0.05). Regression analysis indicated a polynomial relationship between growth parameters and dietary TYM levels. Based upon the varied growth parameters, the optimum dietary TYM level was 1.89% for FCR. TYM at dietary levels of 1.5-2.5 g significantly enhanced liver antioxidant enzyme activity [superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)], immune components in blood [alternative complement activity (C3), total immunoglobulin (Ig), lysozyme activity, bactericidal activity, and total protein], and in mucus [alkaline phosphatase (ALP), protease activity, lysozyme activity, bactericidal activity, and total protein] compared to other diets (P < 0.05). TYM at dietary levels of 2-2.5 g significantly decreased malondialdehyde (MDA) levels compared to other experimental groups (P < 0.05). In addition, use of TYM at dietary levels of 1.5-2.5 g upregulated the expression of the immune-related genes (C3, Lyz, and Ig) (P < 0.05). In contrast, the expression of inflammatory genes, tumor necrosis factor (TNF-α) and Interleukin-8 (IL-8) significantly were downregulated in response to 2-2.5 g TYM (P < 0.05). The hematology of the fish also altered in response to dietary TYM, where the values of corpuscular hemoglobin concentration (MCHC), hemoglobin (Hb), red blood cell (RBC), hematocrit (Hct), and white blood cell (WBC) significantly increased in fish fed 2-2.5 g TYM compared to other diets (P < 0.05). In addition, MCV significantly decreased in response to 2-2.5 g TYM (P < 0.05). After challenge with Streptococcus iniae, the survival rate was significantly higher in fish fed 2-2.5 g TYM compared to other diets (P < 0.05). The results of the present study concluded that TYM in the diet of rainbow trout can improve the fish growth and immunity and increase the resistance of the fish to Streptococcus iniae infection. The results of this study recommend an optimized dietary level of 2-2.5 g TYM for the fish.

CAR-engineered NK cells; a promising therapeutic option for treatment of hematological malignancies.

Adoptive cell therapy has received a great deal of interest in the treatment of advanced cancers that are resistant to traditional therapy. The tremendous success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells in the treatment of cancer, especially hematological cancers, has exposed CAR's potential. However, the toxicity and significant limitations of CAR-T cell immunotherapy prompted research into other immune cells as potential candidates for CAR engineering. NK cells are a major component of the innate immune system, especially for tumor immunosurveillance. They have a higher propensity for immunotherapy in hematologic malignancies because they can detect and eliminate cancerous cells more effectively. In comparison to CAR-T cells, CAR-NK cells can be prepared from allogeneic donors and are safer with a lower chance of cytokine release syndrome and graft-versus-host disease, as well as being a more efficient antitumor activity with high efficiency for off-the-shelf production. Moreover, CAR-NK cells may be modified to target various antigens while also increasing their expansion and survival in vivo. Extensive preclinical research has shown that NK cells can be effectively engineered to express CARs with substantial cytotoxic activity against both hematological and solid tumors, establishing evidence for potential clinical trials of CAR-NK cells. In this review, we discuss recent advances in CAR-NK cell engineering in a variety of hematological malignancies, as well as the main challenges that influence the outcomes of CAR-NK cell-based tumor immunotherapies.

Mesenchymal Stem/Stromal Cell-Based Delivery: A Rapidly Evolving Strategy for Cancer Therapy.

Mesenchymal stem/stromal cell (MSC)-based therapy has become an attractive and advanced scientific research area in the context of cancer therapy. This interest is closely linked to the MSC-marked tropism for tumors, suggesting them as a rational and effective vehicle for drug delivery for both hematological and solid malignancies. Nonetheless, the therapeutic application of the MSCs in human tumors is still controversial because of the induction of several signaling pathways largely contributing to tumor progression and metastasis. In spite of some evidence supporting that MSCs may sustain cancer pathogenesis, increasing proofs have indicated the suppressive influences of MSCs on tumor cells. During the last years, a myriad of preclinical and some clinical studies have been carried out or are ongoing to address the safety and efficacy of the MSC-based delivery of therapeutic agents in diverse types of malignancies. A large number of studies have focused on the MSC application as delivery vehicles for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), chemotherapeutic drug such as gemcitabine (GCB), paclitaxel (PTX), and doxorubicin (DOX), prodrugs such as 5-fluorocytosine (5-FC) and ganciclovir (GCV), and immune cell-activating cytokines along with oncolytic virus. In the current review, we evaluate the latest findings rendering the potential of MSCs to be employed as potent gene/drug delivery vehicle for inducing tumor regression with a special focus on the in vivo reports performed during the last two decades.