The Role of Ferroptosis in the Pathogenesis of Osteoarthritis.

Osteoarthritis (OA) is the most common type of arthritis. Its high prevalence, especially in the elderly, and its negative impact on physical function make it a leading cause of disability in the elderly. Joint pain as well joint stiffness are the common classic signs of OA. Chondrocyte death together with loss of articular cartilage integrity are the main pathologic changes in OA. Non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are commonly used for the management of OA; still, their effectiveness is limited, and no therapeutic strategy is able to fully stop OA progression. Ferroptosis is a kind of cell death, distinct from apoptosis and necroptosis, caused by iron-dependent peroxidation of membrane phospholipids that terminates cell life by disintegrating all plasma membranes. It has been suggested that ferroptosis has a critical role in decreased viability of chondrocytes in OA, and here, we review recent findings regarding the pathologic pathways that lead to chondrocyte ferroptosis, and discuss the possible therapeutic utility of ferroptosis inhibition in OA.

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.

Carbon nanoparticles-based hydrogel nanocomposite induces bone repair in vivo.

The main objective of the current study is to fabricate a 3D scaffold using alginate hydrogel implemented with carbon nanoparticles (CNPs) as the filler. The SEM imaging revealed that the scaffold possesses a porous internal structure with interconnected pores. The swelling value of the scaffolds (more than 400%) provides a wet niche for bone cell proliferation and migration. The in vitro evaluations showed that the scaffolds were hemocompatible (with hemolysis induction lower than 5%) and cytocompatible (inducing significant proliferative effect (cell viability of 121 ± 4%, p < 0.05) for AlG/CNPs 10%). The in vivo studies showed that the implantation of the fabricated 3D nanocomposite scaffolds induced a bone-forming effect and mediated bone formation into the induced bone defect. In conclusion, these results implied that the fabricated NFC-integrated 3D scaffold exhibited promising characteristics beneficial for bone regeneration and can be applied as the bone tissue engineering scaffold.

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.

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.

Synthesis characterization of Zn-based MOF and their application in degradation of water contaminants.

Metal-organic frameworks (MOFs) are currently popular porous materials with research and application value in various fields such as medicine and engineering. Aiming at the application of MOFs in photocatalysis, this paper mainly reviews the main synthesis methods of ZnMOFs and the latest research progress of Zn MOF-based photocatalysts to degrade organic pollutants in water, such as organic dyes. This nanomaterial is being used to treat wastewater and has proven to be very efficient because of its exceptionally large surface area and porous nature. The results show that Zn-MOFs are capable of high degradation of the above pollutants and over 90% of degradation was observed in publications. In addition, the reusability percentage was examined and studies showed that the Zn-MOF nanostructure has very good stability and can continue to degrade a high percentage of pollutants after several cycles. This review focuses on Zn-MOFs and their composites. First, the methods of synthesis and characterization of these compounds are given. Finally, the application of these composites in the process of photocatalytic degradation of dye pollutants such as methylene blue, methyl orange, crystal violet, rhodamine B, etc. is explained.

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.

WITHDRAWN: Application of Nanoparticles in the Management of Polycystic Ovary Syndrome

The article has been withdrawn at the request of the Corresponding author.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Epidural Administration of Curcumin-Loaded Polycaprolactone/Gelatin Electrospun Nanofibers for Extended Analgesia After Laminectomy in Rats.

Several clinical studies have reported the analgesic effect of curcumin (Curc) in various situations such as rheumatoid arthritis, osteoarthritis, and postsurgical pain. Therefore, in this work, Curc-loaded electrospun nanofibers (NFs) are designed to evaluate their sustained release on analgesic effect duration in rats after epidural placement via repeated formalin and tail-flick tests. The Curc-loaded polycaprolactone/gelatin NFs (Curc-PCL/GEL NFs) are prepared through an electrospinning technique and introduced to the rat's epidural space after laminectomy. The physicochemical and morphology features of the prepared Curc-PCL/GEL NFs were characterized via FE-SEM, FTIR, and degradation assay. The in vitro and in vivo concentrations of Curc were measured to evaluate the analgesic efficacy of the drug-loaded NFs. Rat nociceptive responses are investigated through repeated formalin and tail-flick tests for 5 weeks after the placement of NFs. Curc had a sustained release from the NFs for 5 weeks, and its local pharmaceutical concentrations were much greater than plasma concentrations. Rat's pain scores in both early and late phases of the formalin test were remarkably decreased in the experimental period. Rat's tail-flick latency was remarkably enhanced and remained constant for up to 4 weeks. Our findings show that the Curc-PCL/GEL NFs can supply controlled release of Curc to induce extended analgesia after laminectomy.

Effects of almond intake on oxidative stress parameters: A systematic review and meta-analysis of clinical trials.

BACKGROUND AND AIMS: Several randomized controlled trials (RCTs) have shown that almonds can improve oxidative stress indices, but the results are controversial. Therefore, the goal of this research was to carry out a systematic review and meta-analysis of all RCTs that evaluated the effect of almonds on selected oxidative stress indices. METHODS: A systematic search was conducted up to April 2022 on PubMed, Scopus, Web of Science, and Google Scholar. We have selected the studies that investigated the effects of almonds on malondialdehyde (MDA), and oxidized low-density lipoprotein (Ox-LDL) levels in adults. Data were pooled by using the random-effects model. The risk of bias in individual studies was assessed using the Cochrane Collaboration risk of bias tool. RESULTS: Seven RCTs involving 424 participants were analyzed. The results indicated that almond intake led to a significant decrease in MDA levels (WMD: - 6.63 nmol/ml; 95 % CI: - 8.72 to - 4.54; P < 0.001). However, no significant effect was observed on Ox-LDL (Hedges' g: - 0.12; 95 % CI: - 0.34 to 0.10; P = 0.28). Sensitivity analysis showed that overall estimates were not affected by the elimination of any study. We did not observe any evidence regarding publication bias. CONCLUSION: The present meta-analysis suggests that almond intake can improve MDA levels and might play a beneficial role in the reinforcement of the antioxidant defense system and amelioration of oxidative stress in adults. There is a need for more studies with larger groups to better estimate this effect.

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.

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.

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.

Exploring the impact of miR-128 in inflammatory diseases: A comprehensive study on autoimmune diseases.

microRNAs (miRNAs) play a crucial role in various biological processes, including immune system regulation, such as cell proliferation, tolerance (central and peripheral), and T helper cell development. Dysregulation of miRNA expression and activity can disrupt immune responses and increase susceptibility to neuroimmune disorders. Conversely, miRNAs have been shown to have a protective role in modulating immune responses and preventing autoimmunity. Specifically, reducing the expression of miRNA-128 (miR-128) in an Alzheimer's disease (AD) mouse model has been found to improve cognitive deficits and reduce neuropathology. This comprehensive review focuses on the significance of miR-128 in the pathogenesis of neuroautoimmune disorders, including multiple sclerosis (MS), AD, Parkinson's disease (PD), Huntington's disease (HD), epilepsy, as well as other immune-mediated diseases such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Additionally, we present compelling evidence supporting the potential use of miR-128 as a diagnostic or therapeutic biomarker for neuroimmune disorders. Collectively, the available literature suggests that targeting miR-128 could be a promising strategy to alleviate the behavioral symptoms associated with neuroimmune diseases. Furthermore, further research in this area may uncover new insights into the molecular mechanisms underlying these disorders and potentially lead to the development of novel therapeutic approaches.

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.

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.

SRF/MRTF-A and liver cirrhosis: Pathologic associations.

Liver cirrhosis results from prolonged and extensive liver fibrosis in which fibrotic tissues replace functional hepatic cells. Chronic liver disease due to various viral, chemical, or metabolic factors initiates hepatic fibrogenesis. Cirrhosis is associated with multiple clinical complications and a poor patient prognosis; therefore, developing novel antifibrotic therapies to prevent cirrhosis is of high priority. Mounting evidence points to the key role of serum response factor (SRF) and myocardin-related transcription factor (MRTF)-A in the pathogenesis of liver fibrosis. SRF is a transcription factor and MRTF-A is a co-activator of SRF and normally resides in the cytoplasm. Upon the induction of fibrotic pathways, MRTF-A translocates into the nucleus and forms the active SRF/MRTF-A complex, leading to the expression of a multitude of fibrotic proteins and components of extracellular matrix. Silencing or inhibiting MRTF-A impedes hepatic stellate cell transdifferentiation into myofibroblasts and slows down the deposition of extracellular matrix in the liver, making it a potential therapeutic target. Here, we review the recent findings regarding the role of the SRF/MRTF-A complex in liver fibrosis and its therapeutic potential for the management of cirrhosis.

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.