Curcumin in the treatment of liver cancer: From mechanisms of action to nanoformulations.

Liver cancer is the sixth most prevalent cancer and ranks third in cancer-related death, after lung and colorectal cancer. Various natural products have been discovered as alternatives to conventional cancer therapy strategies, including radiotherapy, chemotherapy, and surgery. Curcumin (CUR) with antiinflammatory, antioxidant, and antitumor activities has been associated with therapeutic benefits against various cancers. It can regulate multiple signaling pathways, such as PI3K/Akt, Wnt/ß-catenin, JAK/STAT, p53, MAPKs, and NF-ĸB, which are involved in cancer cell proliferation, metastasis, apoptosis, angiogenesis, and autophagy. Due to its rapid metabolism, poor oral bioavailability, and low solubility in water, CUR application in clinical practices is restricted. To overcome these limitations, nanotechnology-based delivery systems have been applied to use CUR nanoformulations with added benefits, such as reducing toxicity, improving cellular uptake, and targeting tumor sites. Besides the anticancer activities of CUR in combating various cancers, especially liver cancer, here we focused on the CUR nanoformulations, such as micelles, liposomes, polymeric, metal, and solid lipid nanoparticles, and others, in the treatment of liver cancer.

CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment.

CXC chemokine receptor type 4 (CXCR4) is a member of the G protein-coupled receptors (GPCRs) superfamily and is specific for CXC chemokine ligand 12 (CXCL12, also known as SDF-1), which makes CXCL12/CXCR4 axis. CXCR4 interacts with its ligand, triggering downstream signaling pathways that influence cell proliferation chemotaxis, migration, and gene expression. The interaction also regulates physiological processes, including hematopoiesis, organogenesis, and tissue repair. Multiple evidence revealed that CXCL12/CXCR4 axis is implicated in several pathways involved in carcinogenesis and plays a key role in tumor growth, survival, angiogenesis, metastasis, and therapeutic resistance. Several CXCR4-targeting compounds have been discovered and used for preclinical and clinical cancer therapy, most of which have shown promising anti-tumor activity. In this review, we summarized the physiological signaling of the CXCL12/CXCR4 axis and described the role of this axis in tumor progression, and focused on the potential therapeutic options and strategies to block CXCR4.

Mesenchymal stem cell-released oncolytic virus: an innovative strategy for cancer treatment.

Oncolytic viruses (OVs) infect, multiply, and finally remove tumor cells selectively, causing no damage to normal cells in the process. Because of their specific features, such as, the ability to induce immunogenic cell death and to contain curative transgenes in their genomes, OVs have attracted attention as candidates to be utilized in cooperation with immunotherapies for cancer treatment. This treatment takes advantage of most tumor cells' inherent tendency to be infected by certain OVs and both innate and adaptive immune responses are elicited by OV infection and oncolysis. OVs can also modulate tumor microenvironment and boost anti-tumor immune responses. Mesenchymal stem cells (MSC) are gathering interest as promising anti-cancer treatments with the ability to address a wide range of cancers. MSCs exhibit tumor-trophic migration characteristics, allowing them to be used as delivery vehicles for successful, targeted treatment of isolated tumors and metastatic malignancies. Preclinical and clinical research were reviewed in this study to discuss using MSC-released OVs as a novel method for the treatment of cancer. Video Abstract.

The emerging crosstalk between atherosclerosis-related microRNAs and Bermuda triangle of foam cells: Cholesterol influx, trafficking, and efflux.

In atherosclerosis, the gradual buildup of lipid particles into the sub-endothelium of damaged arteries leads to numerous lipid alterations. The absorption of these modified lipids by monocyte-derived macrophages in the arterial wall leads to cholesterol accumulation and increases the likelihood of foam cell formation and fatty streak, which is an early characteristic of atherosclerosis. Foam cell formation is related to an imbalance in cholesterol influx, trafficking, and efflux. The formation of foam cells is heavily regulated by various mechanisms, among them, the role of epigenetic factors like microRNA alteration in the formation of foam cells has been well studied. Recent studies have focused on the potential interplay between microRNAs and foam cell formation in the pathogenesis of atherosclerosis; nevertheless, there is significant space to progress in this attractive field. This review has focused to examine the underlying processes of foam cell formation and microRNA crosstalk to provide a deep insight into therapeutic implications in atherosclerosis.

The protective effects of silymarin on the reproductive toxicity: a comprehensive review.

The reproductive system is extremely vulnerable to chemotherapy drugs, ionizing radiation, toxic heavy metals, chemicals, and so on. These harmful stimuli are able to induce oxidative damage, apoptosis, inflammation, and other mechanisms in the reproductive organs, leading to different adverse reproductive effects. It was shown that using medicinal plants (medicinal herbs) can be an effective medication for the prevention and treatment of multiple health conditions. Silymarin is a medicinal herb extract, obtained from the seeds of Silybum marianum. This herbal agent is a nontoxic agent even at relatively high physiological dose values, which suggests that it is safe for use in the treatment of different diseases. The hepato-, neuro-, cardio- and nephro-protective effects of silymarin have been assessed previously. The protective activities of silymarin can point to anti-oxidant, anti-apoptotic, anti-inflammatory, anti-fibrotic, immunomodulatory, and membrane-stabilizing properties. In this review, we aim to summarize current studies on the protective potentials of silymarin against reproductive toxicity. The molecular mechanisms of silymarin protection against cellular toxicity are also studied. Moreover, the findings obtained from improved formulations and delivery systems of silymarin have been addressed.

The association between prenatal exposure to polycyclic aromatic hydrocarbons and childhood intelligence: a systematic review of observational studies.

Exposure to polycyclic aromatic hydrocarbons (PAHs) during pregnancy has been associated with many adverse child health. However, the evidence on such associations with child brain development was not reviewed systemically. Therefore, in this study, we systemically reviewed the observational studies on prenatal exposure to PAHs and childhood intelligence quotient (IQ). The Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines were applied to perform this review. We systematically searched Scopus, PubMed, and Web of Science for all relevant articles published in English until 15 October 2022. The quality of retrieved studies was evaluated based on the Gascon et al. method. We retrieved a total of 351 citations through the initial search, of which an overall of six articles ([Formula: see text] participants) were included in our final review. The quality assessment indicated that four studies had excellent and two studies had good quality. Three reviewed studies reported a significant negative association between prenatal exposure to PAHs and children's IQ. One study reported that exposure to PAHs combined with material hardship was associated with lower child IQ and one study indicated lower child IQ through lower LINE1 DNA methylation-related maternal exposure to PAHs. However, another study did not observe a significant association between prenatal PAH exposure and child IQ. Overall, our review indicated that exposure to PAHs during pregnancy has an adverse impact on childhood IQ.

Recent progressions in biomedical and pharmaceutical applications of chitosan nanoparticles: A comprehensive review.

Nowadays, the most common approaches in the prognosis, diagnosis, and treatment of diseases are along with undeniable limitations. Thus, the ever-increasing need for using biocompatible natural materials and novel practical modalities is required. Applying biomaterials, such as chitosan nanoparticles (CS NPs: FDA-approved long-chain polymer of N-acetyl-glucosamine and D-glucosamine for some pharmaceutical applications), can serve as an appropriate alternative to overcome these limitations. Recently, the biomedical applications of CS NPs have extensively been investigated. These NPs and their derivatives can not only prepare through different physical and chemical approaches but also modify with various molecules and bioactive materials. The potential properties of CS NPs, such as biocompatibility, biodegradability, serum stability, solubility, non-immunogenicity, anti-inflammatory properties, appropriate pharmacokinetics and pharmacodynamics, and so forth, have made them excellent candidates for biomedical applications. Therefore, CS NPs have efficiently applied for various biomedical applications, like regenerative medicine and tissue engineering, biosensors for the detection of microorganisms, and drug delivery systems (DDS) for the suppression of diseases. These NPs possess a high level of biosafety. In summary, CS NPs have the potential ability for biomedical and clinical applications, and it would be remarkably beneficial to develop new generations of CS-based material for the future of medicine.

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.

Smartphone-Facilitated Mobile Colorimetric Probes for Rapid Monitoring of Chemical Contaminations in Food: Advances and Outlook.

Smartphone-derived colorimetric tools have the potential to revolutionize food safety control by enabling citizens to carry out monitoring assays. To realize this, it is of paramount significance to recognize recent study efforts and figure out important technology gaps in terms of food security. Driven by international connectivity and the extensive distribution of smartphones, along with their built-in probes and powerful computing abilities, smartphone-based sensors have shown enormous potential as cost-effective and portable diagnostic scaffolds for point-of-need tests. Meantime, the colorimetric technique is of particular notice because of its benefits of rapidity, simplicity, and high universality. In this study, we tried to outline various colorimetric platforms using smartphone technology, elucidate their principles, and explore their applications in detecting target analytes (pesticide residues, antibiotic residues, metal ions, pathogenic bacteria, toxins, and mycotoxins) considering their sensitivity and multiplexing capability. Challenges and desired future perspectives for cost-effective, accurate, reliable, and multi-functions smartphone-based colorimetric tools have also been debated.

Advances in Biosensing of Chemical Food Contaminants Based on the MOFs-Graphene Nanohybrids.

Food safety issue is becoming an international challenge for human health owing to the presence of contaminants. In this context, reliable, rapid, and sensitive detecting technology is extremely demanded to establish food safety assurance systems. MOFs (Metal-organic frameworks) are a new type of porous crystalline material with particular physical and chemical characteristics presented in food safety requirements. (Bio)sensors driven MOF materials have emerged as a promising alternative and complementary analytical techniques, owing to their great specific area, high porosity, and uniform and fine-tunable pore buildings. Nevertheless, the insufficient stability and electrical conductivity of classical MOFs limit their utilization. Employing graphene-derived nanomaterials with high functional elements as patterns for the MOF materials not only improves the structural instability and poor conductivity but also impedes the restacking and aggregation between graphene layers, thus significantly extending the MOFs application. A review of MOFs-graphene-based material used in food contamination detection is urgently needed for encouraging the advance of this field. Herein, this paper systematically outlines current breakthroughs in MOF-graphene-based nanoprobes, outlines their principles, and illustrates their employments in identifying mycotoxins, heavy metal ions, pathogens, antibiotics, and pesticides, referring to their multiplexing and sensitivity ability. The challenges and limitations of applying MOF-graphene composite for precise and efficient assessment of food were also debated. This paper would maybe offer some inspired concepts for an upcoming study on MOF-based composites in the food security context.

The radioprotective potentials of silymarin/silibinin against radiotherapy-induced toxicities: A systematic review of clinical and experimental studies.

BACKGROUND: Although radiotherapy is one of the main cancer treatment modalities, exposing healthy organs/tissues to ionizing radiation during treatment can lead to different adverse effects. In this regard, it has been shown that the use of radioprotective agents may alleviate the ionizing radiation-induced toxicities. OBJECTIVE: The present study aims to review the radioprotective potentials of silymarin/silibinin in the prevention/reduction of ionizing radiation-induced adverse effects on healthy cells/tissues. METHODS: Based on PRISMA guideline, a comprehensive and systematic search was performed for identifying relevant literature on the "potential protective role of silymarin/silibinin in the treatment of radiotherapy-induced toxicities" in the different electronic databases of Web of Science, PubMed, and Scopus up to April 2022. Four hundred and fifty-five articles were obtained and screened in accordance with the inclusion and exclusion criteria of the current study. Finally, 19 papers were included in this systematic review. RESULTS: The findings revealed that the ionizing radiation-treated groups had reduced survival rate and body weight in comparison with the control groups. It was also found that radiation can induce mild to severe adverse effects on skin, digestive, hematologic, lymphatic, respiratory, reproductive, and urinary systems. Nevertheless, the administration of silymarin/silibinin could mitigate the ionizing radiation-induced adverse effects in most cases. This herbal agent exerts its radioprotective effects through anti-oxidant, anti-apoptosis, anti-inflammatory activities, and other mechanisms. CONCLUSION: The results of the current systematic review showed that co-treatment of silymarin/silibinin with radiotherapy alleviates the radiotherapy-induced adverse effects in healthy cells/tissues.

Stem cell-derived exosomes in bone healing: focusing on their role in angiogenesis.

Fractures in bone, a tissue critical in protecting other organs, affect patients' quality of life and have a heavy economic burden on societies. Based on regenerative medicine and bone tissue engineering approaches, stem cells have become a promising and attractive strategy for repairing bone fractures via differentiation into bone-forming cells and production of favorable mediators. Recent evidence suggests that stem cell-derived exosomes could mediate the therapeutic effects of their counterpart cells and provide a cell-free therapeutic strategy in bone repair. Since bone is a highly vascularized tissue, coupling angiogenesis and osteogenesis is critical in bone fracture healing; thus, developing therapeutic strategies to promote angiogenesis will facilitate bone regeneration and healing. To this end, stem cell-derived exosomes with angiogenic potency have been developed to improve fracture healing. This review summarizes the effects of stem cell-derived exosomes on the repair of bone tissue, focusing on the angiogenesis process.

Concanavalin A as a promising lectin-based anti-cancer agent: the molecular mechanisms and therapeutic potential.

Concanavalin A (ConA), the most studied plant lectin, has been known as a potent anti-neoplastic agent for a long time. Since initial reports on its capacity to kill cancer cells, much attention has been devoted to unveiling the lectin's exact molecular mechanism. It has been revealed that ConA can bind to several receptors on cancerous and normal cells and modulate the related signaling cascades. The most studied host receptor for ConA is MT1-MMP, responsible for most of the lectin's modulations, ranging from activating immune cells to killing tumor cells. In this study, in addition to studying the effect of ConA on signaling and immune cell function, we will focus on the most up-to-date advancements that unraveled the molecular mechanisms by which ConA can induce autophagy and apoptosis in various cancer cell types, where it has been found that P73 and JAK/STAT3 are the leading players. Moreover, we further discuss the main signaling molecules causing liver injury as the most significant side effect of the lectin injection. Altogether, these findings may shed light on the complex signaling pathways controlling the diverse responses created via ConA treatment, thereby modulating these complex networks to create more potent lectin-based cancer therapy. Video Abstract.

A novel approach based on the ultrasonic-assisted microwave method for the efficient synthesis of Sc-MOF@SiO2 core/shell nanostructures for H2S gas adsorption: A controllable systematic study for a green future.

In this work, for the first time, novel Sc-MOF@SiO2 core/shell nanostructures have been synthesized under the optimal conditions of ultrasonic-assisted microwave routes. The final products showed small particle size distributions with homogeneous morphology (SEM results), high thermal stability (TG curve), high surface area (BET adsorption/desorption techniques), and significant porosity (BJH method). The final nanostructures of Sc-MOF@SiO2 core/shell with such distinct properties were used as a new compound for H2S adsorption. It was used with the systematic investigation based on a 2K-1 factorial design, which showed high-performance adsorption of about 5 mmol/g for these novel adsorbents; the optimal experimental conditions included pressure, 1.5 bar; contact time, 20 min; and temperature, 20°C. This study and its results promise a green future for the potential control of gas pollutants.

Ketoprofen suppresses triple negative breast cancer cell growth by inducing apoptosis and inhibiting autophagy.

BACKGROUND: Triple-negative breast cancer (TNBC) is an invasive phenotype with undesirable clinical features, poor prognosis, and therapy resistance. Ketoprofen is a Non-steroidal anti-inflammatory drug (NSAID) with anti-tumor properties. AIM: To investigate the effects of Ketoprofen on apoptosis and autophagy in TNBC cell line MDA-MB-231. METHODS: The cytotoxic activity of Ketoprofen was assayed by the MTS method. Flowcytometry was utilized to measure the number of apoptotic MDA-MB-231 cells. The expression levels of apoptosis and autophagy markers, JAK2 and STAT3 were determined using quantitative real time-PCR (qRT-PCR) and western blotting methods. RESULTS: Ketoprofen significantly decreased the proliferation of MDA-MB-231 cells compared to control cells. It also considerably induced apoptosis and apoptotic markers in these cells in comparison to controls. Treating the MADA-MB-231 cell line with Ketoprofen had an inhibitory effect on autophagy markers in this cell line. The use of FasL, as a death ligand, and ZB4, as an antibody that blocks the extrinsic pathway of apoptosis, revealed the involvement of the extrinsic pathway in the apoptosis-stimulating effect of Ketoprofen in the MADA-MB-231 cell line. Ketoprofen also hindered the phosphorylation and activation of JAK2 and STAT molecules leading to the inhibition of the JAK/STAT pathway in this TNBC cell line. CONCLUSION: The outcomes of this study uncovered the anti-TNBC activity of Ketoprofen by inducing apoptosis and inhibiting viability and autophagy in MADA-MB-231 cells. Our data also suggested that Ketoprofen impedes apoptosis in TNBC cells by two different mechanisms including the induction of the extrinsic apoptotic pathway and inhibition of the JAK/STAT signaling.

Phosphate Ion Removal from Synthetic and Real Wastewater Using MnFe2O4 Nanoparticles: A Reusable Adsorbent.

The purpose of this study was to eliminate phosphate (P) from wastewater using MnFe2O4 nanoparticles. BET, TGA/DTG, FTIR, SEM, TEM, VSM, XRD and EDX/Map analyses were used to determine the MnFe2O4 surface properties. The specific surface area of the adsorbent was 196.56 m2/g and VSM analysis showed that the adsorbent has a ferromagnetic property. The maximum P sorption efficiency using MnFe2O4 (98.52%) was achieved at pH 6, temperature of 55 °C, P concentration of 10 mg/L, time of 60 min, and sorbent dosage of 2.5 g/L, which is a significant value. Also, the thermodynamic study indicated that the P sorption process is spontaneous and endothermic. Moreover, the utmost sorption capacity of P using MnFe2O4 was 39.48 mg/g. Besides, MnFe2O4 can be used for up to 6 reuse cycles with high sorption efficiency (>91%). Also, MnFe2O4 was able to remove phosphate, COD, and BOD5 from municipal wastewater with considerable removal efficiencies of 82.7%, 75.8%, and 77.3%, respectively.

Functions and therapeutic interventions of non-coding RNAs associated with TLR signaling pathway in atherosclerosis.

Nowadays, emerging data demonstrate that the toll-like receptor (TLR) signaling pathway plays an important role in the progression of inflammatory atherosclerosis. Indeed, dysregulated TLR signaling pathway could be a cornerstone of inflammation and atherosclerosis, which contributes to the development of cardiovascular diseases. It is interesting to note that this pathway is heavily controlled by several mechanisms, such as epigenetic factors in which the role of non-coding RNAs (ncRNAs), particularly microRNAs and long noncoding RNAs as well as circular RNAs in the pathogenesis of atherosclerosis has been well studied. Recent years have seen a significant surge in the amount of research exploring the interplay between ncRNAs and TLR signaling pathway downstream targets in the development of atherosclerosis; however, there is still considerable room for improvement in this field. The current study was designed to review underlying mechanisms of TLR signaling pathway and ncRNA interactions to shed light on therapeutic implications in patients with atherosclerosis.

Mitofusin-2 in cancer: Friend or foe?

Cancer is a category of disorders characterized by excessive cell proliferation with the ability to infiltrate or disseminate to other organs of the body. Mitochondrial dysfunction, as one of the most prominent hallmarks of cancer cells, has been related to the onset and development of various cancers. Mitofusin 2 (MFN2) is a major mediator of mitochondrial fusion, endoplasmic reticulum (ER)-mitochondria interaction, mitophagy and axonal transport of mitochondria. Available data have shown that MFN2, which its alterations have been associated with mitochondrial dysfunction, could affect cancer initiation and progression. In fact, it showed that MFN2 may have a double-edged sword effect on cancer fate. Precisely, it demonstrated that MFN2, as a tumor suppressor, induces cancer cell apoptosis and inhibits cell proliferation via Ca2+ and Bax-mediated apoptosis and increases P21 and p27 levels, respectively. It also could suppress cell survival via inhibiting PI3K/Akt, Ras-ERK1/2-cyclin D1 and mTORC2/Akt signaling pathways. On the other hand, MFN2, as an oncogene, could increase cancer invasion via snail-mediated epithelial-mesenchymal transition (EMT) and in vivo tumorigenesis. While remarkable progress has been achieved in recent decades, further exploration is required to elucidate whether MFN2 could be a friend or it's an enemy. This study aimed to highlight the different functions of MFN2 in various cancers.

Synthesis of efficient cobalt-metal organic framework as reusable nanocatalyst in the synthesis of new 1,4-dihydropyridine derivatives with antioxidant activity.

Efficient cobalt-metal organic framework (Co-MOF) was prepared via a controllable microwave-assisted reverse micelle synthesis route. The products were characterized by SEM image, N2 adsorption/desorption isotherm, FTIR spectrum, and TG analysis. Results showed that the products have small particle size distribution, homogenous morphology, significant surface area, and high thermal stability. The physicochemical properties of the final products were remarkable compared with other MOF samples. The newly synthesized nanostructures were used as recyclable catalysts in the synthesis of 1,4-dihydropyridine derivatives. After the confirmation of related structures, the antioxidant activity of derivatives based on the DPPH method was evaluated and the relationship between structures and antioxidant activity was observed. In addition to recyclability, the catalytic activity of Co-MOF studied in this research has remarkable effects on the synthesis of 1,4 dihydropyridine derivatives.