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.

Malignant function of nuclear factor-kappaB axis in prostate cancer: Molecular interactions and regulation by non-coding RNAs.

Prostate carcinoma is a malignant situation that arises from genomic alterations in the prostate, leading to changes in tumorigenesis. The NF-κB pathway modulates various biological mechanisms, including inflammation and immune responses. Dysregulation of NF-κB promotes carcinogenesis, including increased proliferation, invasion, and therapy resistance. As an incurable disease globally, prostate cancer is a significant health concern, and research into genetic mutations and NF-κB function has the efficacy to facilitate the introduction of novel therapies. NF-κB upregulation is observed during prostate cancer progression, resulting in increased cell cycle progression and proliferation rates. Additionally, NF-κB endorses resistance to cell death and enhances the capacity for metastasis, particularly bone metastasis. Overexpression of NF-κB triggers chemoresistance and radio-resistance, and inhibition of NF-κB by anti-tumor compounds can reduce cancer progression. Interestingly, non-coding RNA transcripts can regulate NF-κB level and its nuclear transfer, offering a potential avenue for modulating prostate cancer progression.

Nanotechnology-empowered lung cancer therapy: From EMT role in cancer metastasis to application of nanoengineered structures for modulating growth and metastasis.

Lung cancer is one of the leading causes of death in both males and females, and it is the first causes of cancer-related deaths. Chemotherapy, surgery and radiotherapy are conventional treatment of lung cancer and recently, immunotherapy has been also appeared as another therapeutic strategy for lung tumor. However, since previous treatments have not been successful in cancer therapy and improving prognosis and survival rate of lung tumor patients, new studies have focused on gene therapy and targeting underlying molecular pathways involved in lung cancer progression. Nanoparticles have been emerged in treatment of lung cancer that can mediate targeted delivery of drugs and genes. Nanoparticles protect drugs and genes against unexpected interactions in blood circulation and improve their circulation time. Nanoparticles can induce phototherapy in lung cancer ablation and mediating cell death. Nanoparticles can induce photothermal and photodynamic therapy in lung cancer. The nanostructures can impair metastasis of lung cancer and suppress EMT in improving drug sensitivity. Metastasis is one of the drawbacks observed in lung cancer that promotes migration of tumor cells and allows them to establish new colony in secondary site. EMT can occur in lung cancer and promotes tumor invasion. EMT is not certain to lung cancer and it can be observed in other human cancers, but since lung cancer has highest incidence rate, understanding EMT function in lung cancer is beneficial in improving prognosis of patients. EMT induction in lung cancer promotes tumor invasion and it can also lead to drug resistance and radio-resistance. Moreover, non-coding RNAs and pharmacological compounds can regulate EMT in lung cancer and EMT-TFs such as Twist and Slug are important modulators of lung cancer invasion that are discussed in current review.

Harnessing function of EMT in hepatocellular carcinoma: From biological view to nanotechnological standpoint.

Management of cancer metastasis has been associated with remarkable reduction in progression of cancer cells and improving survival rate of patients. Since 90% of mortality are due to cancer metastasis, its suppression can improve ability in cancer fighting. The EMT has been an underlying cause in increasing cancer migration and it is followed by mesenchymal transformation of epithelial cells. HCC is the predominant kind of liver tumor threatening life of many people around the world with poor prognosis. Increasing patient prognosis can be obtained via inhibiting tumor metastasis. HCC metastasis modulation by EMT and HCC therapy by nanoparticles are discussed here. First of all, EMT happens during progression and advanced stages of HCC and therefore, its inhibition can reduce tumor malignancy. Moreover, anti-cancer compounds including all-trans retinoic acid and plumbaging, among others, have been considered as inhibitors of EMT. The EMT association with chemoresistance has been evaluated. Moreover, ZEB1/2, TGF-ß, Snail and Twist are EMT modulators in HCC and enhancing cancer invasion. Therefore, EMT mechanism and related molecular mechanisms in HCC are evaluated. The treatment of HCC has not been only emphasized on targeting molecular pathways with pharmacological compounds and since drugs have low bioavailability, their targeted delivery by nanoparticles promotes HCC elimination. Moreover, nanoparticle-mediated phototherapy impairs tumorigenesis in HCC by triggering cell death. Metastasis of HCC and even EMT mechanism can be suppressed by cargo-loaded nanoparticles.

Apigenin in cancer therapy: Prevention of genomic instability and anticancer mechanisms.

The incidence of cancer has been growing worldwide. Better survival rates following the administration of novel drugs and new combination therapies may concomitantly cause concern regarding the long-term adverse effects of cancer therapy, for example, second primary malignancies. Moreover, overcoming tumour resistance to anticancer agents has been long considered as a critical challenge in cancer research. Some low toxic adjuvants such as herb-derived molecules may be of interest for chemoprevention and overcoming the resistance of malignancies to cancer therapy. Apigenin is a plant-derived molecule with attractive properties for chemoprevention, for instance, promising anti-tumour effects, which may make it a desirable adjuvant to reduce genomic instability and the risks of second malignancies among normal tissues. Moreover, it may improve the efficiency of anticancer modalities. This paper aims to review various effects of apigenin in both normal tissues and malignancies. In addition, we explain how apigenin may have the ability to protect usual cells against the genotoxic repercussions following radiotherapy and chemotherapy. Furthermore, the inhibitory effects of apigenin on tumours will be discussed.

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.

Coronavirus disease 2019 (COVID-19) update: From metabolic reprogramming to immunometabolism.

The field of immunometabolism investigates and describes the effects of metabolic rewiring in immune cells throughout activation and the fates of these cells. Recently, it has been appreciated that immunometabolism plays an essential role in the progression of viral infections, cancer, and autoimmune diseases. Regarding COVID-19, the aberrant immune response underlying the progression of diseases establishes two major respiratory pathologies, including acute respiratory distress syndrome (ARDS) or pneumonia-induced acute lung injury (ALI). Both innate and adaptive immunity (T cell-based) were impaired in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Current findings have deciphered that macrophages (innate immune cells) are involved in the inflammatory response seen in COVID-19. It has been demonstrated that immune system cells can change metabolic reprogramming in some conditions, including autoimmune diseases, cancer, and infectious disease, including COVID-19. The growing findings on metabolic reprogramming in COVID-19 allow an exploration of metabolites with immunomodulatory properties as future therapies to combat this hyperinflammatory response. The elucidation of the exact role and mechanism underlying this metabolic reprograming in immune cells could help apply more precise approaches to initial diagnosis, prognosis, and in-hospital therapy. This report discusses the latest findings from COVID-19 on host metabolic reprogramming and immunometabolic responses.

CAR-T cell combination therapy: the next revolution in cancer treatment.

In recent decades, the advent of immune-based therapies, most notably Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment. The promising results of numerous studies indicate that CAR-T cell therapy has had a remarkable ability and successful performance in treating blood cancers. However, the heterogeneity and immunosuppressive tumor microenvironment (TME) of solid tumors have challenged the effectiveness of these anti-tumor fighters by creating various barriers. Despite the promising results of this therapeutic approach, including tumor degradation and patient improvement, there are some concerns about the efficacy and safety of the widespread use of this treatment in the clinic. Complex and suppressing tumor microenvironment, tumor antigen heterogeneity, the difficulty of cell trafficking, CAR-T cell exhaustion, and reduced cytotoxicity in the tumor site limit the applicability of CAR-T cell therapy and highlights the requiring to improve the performance of this treatment. With this in mind, in the last decade, many efforts have been made to use other treatments for cancer in combination with tuberculosis to increase the effectiveness of CAR-T cell therapy, especially in solid tumors. The combination therapy results have promising consequences for tumor regression and better cancer control compared to single therapies. Therefore, this study aimed to comprehensively discuss different cancer treatment methods in combination with CAR-T cell therapy and their therapeutic outcomes, which can be a helpful perspective for improving cancer treatment in the near future.

Cancer combination therapies by angiogenesis inhibitors; a comprehensive review.

Abnormal vasculature is one of the most conspicuous traits of tumor tissue, largely contributing to tumor immune evasion. The deregulation mainly arises from the potentiated pro-angiogenic factors secretion and can also target immune cells' biological events, such as migration and activation. Owing to this fact, angiogenesis blockade therapy was established to fight cancer by eliminating the nutrient and oxygen supply to the malignant cells by impairing the vascular network. Given the dominant role of vascular-endothelium growth factor (VEGF) in the angiogenesis process, the well-known anti-angiogenic agents mainly depend on the targeting of its actions. However, cancer cells mainly show resistance to anti-angiogenic agents by several mechanisms, and also potentiated local invasiveness and also distant metastasis have been observed following their administration. Herein, we will focus on clinical developments of angiogenesis blockade therapy, more particular, in combination with other conventional treatments, such as immunotherapy, chemoradiotherapy, targeted therapy, and also cancer vaccines. Video abstract.

Detection of HPV16 viral load in L2 gene as a related predictor of cervical cancer among women in Dhi-Qar province by qRT-PCR.

BACKGROUND: The most common infection among young women that increases the risk of developing cervical cancer (CC) is human papillomavirus (HPV). In this study, we are going to assess whether HPV16 DNA concentration helps indicate cervical cancer progression ,As well as for age groups and their relationship to cervical cancer. METHODS: Present study included 93 adult females suffering from cervical cancer during the period from 2017 to 2020. Molecular detection of HPV was done using amplification of the L2 gene (minor capsid protein). RESULTS: Present results showed that 60 (65%) of the patients from 93 cervical cancer cases were infected by HPV16 while only 5 (8%) of healthy patients from the control group were positive for HPV16. So, the current study revealed high HPV16 load in cervical cancer ranged from 1.09 × 102 IU/ml to 5.07 × 103 IU/ml with a mean ± SD of viral load was 1043.25 ± 8.50 IU/ml while in healthy individuals very low viral load ranging from 88 IU/ml to 101 IU/ml and mean ± SD of viral load was 91.25 ± 2.90 IU/ml was reported. CONCLUSION: HPV16 viral load is significantly associated with cervical carcinoma among women in Dhi-Qar Province.

Apigenin alleviates resistance to doxorubicin in breast cancer cells by acting on the JAK/STAT signaling pathway.

BACKGROUND: Breast cancer is the most frequent cancer among women. Despite the effectiveness of Doxorubicin (DOX) as a chemotherapeutic for the treatment of breast cancer, the therapy-resistance remains unsolvable. Apigenin is a natural dietary flavonoid with potential anticancer activities. Our study's intention was to evaluate the effect of Apigenin on DOX resistance in MCF-7 cells. METHODS: DOX-resistant MCF-7 cell line (MCF-7R) was developed by treating MCF-7 cells with increasing concentrations of DOX (0-100 µM). The viability of cell lines was assayed using MTT method. Quantitative polymerase chain reaction method was performed to measure multidrug-resistance 1 (MDR1) gene expression level. The expression of MDR1, Janus kinase 2 (JAK2) and Signal transducer and activator of transcription 3 (STAT3) proteins were determined by western blotting. RESULTS: MCF-7R cell line showed resistance to DOX in comparison to MCF-7 cells. Apigenin had a significant effect on the reduction of viability of both MCF-7 and MCF-7R cell lines. However, DOX-resistance in the MCF-7 cell line was considerably decreased due to the co-treatment of MCF-7R cells with Apigenin. This natural compound also downregulated the expression of MDR1 at mRNA and protein levels both in resistant and non-resistant cells. Apigenin significantly prohibited the phosphorylation and activation of JAK2 and STAT3 proteins both in MCF-7 and MCF-7R cell lines. CONCLUSIONS: The present results suggested, for the first time, Apigenin as an ideal therapeutic for ameliorating DOX resistance in breast cancer. These data also proposed a novel mechanism for the anti-resistance activity of Apigenin by regulating the JAK2/STAT3/MDR1 axis.

Pathogenic role of 25-hydroxycholesterol in cancer development and progression.

Cholesterol is an essential lipid that serves several important functions, including maintaining the homeostasis of cells, acting as a precursor to bile acid and steroid hormones and preserving the stability of membrane lipid rafts. 25-hydroxycholesterol (25-HC) is a cholesterol derivative that may be formed from cholesterol. 25-HC is a crucial component in various biological activities, including cholesterol metabolism. In recent years, growing evidence has shown that 25-HC performs a critical function in the etiology of cancer, infectious diseases and autoimmune disorders. This review will summarize the latest findings regarding 25-HC, including its biogenesis, immunomodulatory properties and role in innate/adaptive immunity, inflammation and the development of various types of cancer.

Folate-Targeted Curcumin-Loaded Niosomes for Site-Specific Delivery in Breast Cancer Treatment: In Silico and In Vitro Study.

As the most common cancer in women, efforts have been made to develop novel nanomedicine-based therapeutics for breast cancer. In the present study, the in silico curcumin (Cur) properties were investigated, and we found some important drawbacks of Cur. To enhance cancer therapeutics of Cur, three different nonionic surfactants (span 20, 60, and 80) were used to prepare various Cur-loaded niosomes (Nio-Cur). Then, fabricated Nio-Cur were decorated with folic acid (FA) and polyethylene glycol (PEG) for breast cancer suppression. For PEG-FA@Nio-Cur, the gene expression levels of Bax and p53 were higher compared to free drug and Nio-Cur. With PEG-FA-decorated Nio-Cur, levels of Bcl2 were lower than the free drug and Nio-Cur. When MCF7 and 4T1 cell uptake tests of PEG-FA@Nio-Cur and Nio-Cur were investigated, the results showed that the PEG-FA-modified niosomes exhibited the most preponderant endocytosis. In vitro experiments demonstrate that PEG-FA@Nio-Cur is a promising strategy for the delivery of Cur in breast cancer therapy. Breast cancer cells absorbed the prepared nanoformulations and exhibited sustained drug release characteristics.

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.

CAR-NK cell in cancer immunotherapy; A promising frontier.

Chimeric antigen receptors (CARs) have a unique facet of synthetic biology and offer a paradigm shift in personalized medicine as they can use and redirect the patient's immune cells to attack cancer cells. CAR-natural killer (NK) cells combine the targeted specificity of antigens with the subsequent intracellular signaling ability of the receptors to increase their anti-cancer functions. Importantly, CAR-NK cells can be utilized as universal cell-based therapy without requiring human leukocyte antigen (HLA) matching or earlier contact with tumor-associated antigens (TAAs). Indeed, CAR-NK cells can be adapted to recognize various antigens, hold higher proliferation capacity, and in vivo persistence, show improved infiltration into the tumors, and the ability to overcome the resistant tumor microenvironment leading to sustained cytotoxicity against tumors. Accumulating evidence from recent in vivo studies rendering CAR-NK cell anti-cancer competencies renewed the attention in the context of cancer immunotherapy, as these redirected effector cells can be used in the development of the "off-the-shelf" anti-cancer immunotherapeutic products. In the current review, we focus on the therapeutic efficacy of CAR-NK cell therapies for treating various human malignancies, including hematological malignancies and solid tumors, and will discuss the recent findings in this regard, with a special focus on animal studies.

A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine.

Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

The use of combination therapy for the improvement of colistin activity against bacterial biofilm.

Colistin is used as a last resort for the management of infections caused by multi-drug resistant (MDR) bacteria. However, the use of this antibiotic could lead to different side effects, such as nephrotoxicity, in most patients, and the high prevalence of colistin-resistant strains restricts the use of colistin in the clinical setting. Additionally, colistin could induce resistance through the increased formation of biofilm; biofilm-embedded cells are highly resistant to antibiotics, and as with other antibiotics, colistin is impaired by bacteria in the biofilm community. In this regard, the researchers used combination therapy for the enhancement of colistin activity against bacterial biofilm, especially MDR bacteria. Different antibacterial agents, such as antimicrobial peptides, bacteriophages, natural compounds, antibiotics from different families, N-acetylcysteine, and quorum-sensing inhibitors, showed promising results when combined with colistin. Additionally, the use of different drug platforms could also boost the efficacy of this antibiotic against biofilm. The mentioned colistin-based combination therapy not only could suppress the formation of biofilm but also could destroy the established biofilm. These kinds of treatments also avoided the emergence of colistin-resistant subpopulations, reduced the required dosage of colistin for inhibition of biofilm, and finally enhanced the dosage of this antibiotic at the site of infection. However, the exact interaction of colistin with other antibacterial agents has not been elucidated yet; therefore, further studies are required to identify the precise mechanism underlying the efficient removal of biofilms by colistin-based combination therapy.