The synergistic effects of betanin and radiotherapy in a prostate cancer cell line: an in vitro study.

BACKGROUND: Prostate cancer is among the most common cancers in men with an increasing incidence rate. Radiation therapy (RT) is a therapeutic strategy for the management of prostate cancer after surgery; nonetheless, it has different side effects on neighboring healthy cells/tissues. Moreover, radioresistance has been an increasing phenomenon in the recent years. Therefore, there is an urgent need for the introduction of a safe and effective radiosensitizing agent. Accordingly, the recent trend in the development of novel drugs is accompanied by a push toward natural compounds. Our study evaluated the effects of betanin combined with RT as a potential radiosensitizing agent in the PC-3 cell line. METHODS AND RESULTS: MTT assay was utilized to determine the growth inhibitory impact of betanin. The possible synergistic effect was evaluated with CompuSyn software upon Trypan blue exclusion test. Apoptosis-related gene expression was evaluated via Real-time PCR and the protein expression of P21 was determined using western blotting. A synergistic anticancer effect with an optimal combination index of 0.61 was achieved by treating PC-3 cells with betanin and RT. The results pointed out that betanin synergistically triggered RT-mediated apoptosis and cell cycle arrest through modulating gene and protein expression in comparison with each of the monotherapies. CONCLUSION: These findings shed light on the synergistic antitumor effect of betanin and RT in prostate cancer, indicating the potential use of betanin as a radiosensitizer agent.

Ultrastructural characteristics of the accumulation of iron nanoparticles in the intestine of Cyprinus carpio (Linnaeus, 1758) under aquaculture.

During the development of nanotechnology, the production of many substances containing nanoparticles leads to the release of various nanoparticles into the environment, including the water ecosystem. The main goal of the current research was to study the ultrastructural characteristics of the entry and bioaccumulation of Fe3O4 nanoparticles in the small intestine of Cyprinus carpio (Linnaeus, 1758), as well as the pathomorphological changes in the fish organism. Two different doses (10 and 100 mg) of Fe3O4 nanoparticles were fed to fingerlings for 7 days and then intestinal samples were taken and studied. It was found that the extent of damages was boosted within the increment of nanoparticle concentration. The sequence and bioaccumulation of Fe3O4 nanoparticles in the small intestine of fish occurred as below: firstly, the nanoparticles passed into microvilli located in the apical part of enterocytes in the mucosa layer, from there into the cytoplasm of the epithelial cells, including cytoplasmatic organelles (nucleus, mitochondria, lysosomes, fat granules), and then into a lamina propria of the mucosa of the small intestine and passed into the endothelium of the blood vessels and to the erythrocytes of the vessels which located in the lumen. It was determined that although the nanoparticles were up to 30 nm in size, only particles with a maximum size of 20 nm could penetrate the intestinal wall. Thus, the release of Fe3O4 nanoparticles into the environment in high doses has a negative effect on the living ecosystem, including the body of fish living in the water.

Stem cells technology as a platform for generating reproductive system organoids and treatment of infertility-related diseases.

In recent years, stem cells have known as a helpful biological tool for the accurate diagnosis, treatment and recognition of diseases. Using stem cells as biomarkers have presented high potential in the early detection of many diseases. Another advancement in stem cell technology includes stem cell derived organoids model that could be a promising platform for diagnosis and modeling different diseases. Furthermore, therapeutic capabilities of stem cell therapy have increased hope in the face of different disability managements. All of these technologies are also widely used in reproductive related diseases especially in today's world that many couples encounter infertility problems. However, with the aid of numerous improvements in the treatment of infertility, over 80% of couples who dreamed of having children could now have children. Due to the fact that infertility has many negative effects on personal and social lives of young couples, many researchers have focused on the treatment of male and female reproductive system abnormalities with different types of stem cells, including embryonic stem cells, bone marrow mesenchymal stem cells (MSCs), and umbilical cord-derived MSCs. Also, design and formation of reproductive system organoids provide a fascinating window into disease modeling, drug screening, personalized therapy, and regeneration medicine. Utilizing these techniques to study, model and treat the infertility-related diseases has drawn attention of many scientists. This review explains different applications of stem cells in generating reproductive system organoids and stem cell-based therapies for male and female infertility related diseases treatment.

Covid-19 and kidney injury: Pathophysiology and molecular mechanisms.

The novel coronavirus (SARS-CoV-2) has turned into a life-threatening pandemic disease (Covid-19). About 5% of patients with Covid-19 have severe symptoms including septic shock, acute respiratory distress syndrome, and the failure of several organs, while most of them have mild symptoms. Frequently, the kidneys are involved through direct or indirect mechanisms. Kidney involvement mainly manifests itself as proteinuria and acute kidney injury (AKI). The SARS-CoV-2-induced kidney damage is expected to be multifactorial; directly it can infect the kidney podocytes and proximal tubular cells and based on an angiotensin-converting enzyme 2 (ACE2) pathway it can lead to acute tubular necrosis, protein leakage in Bowman's capsule, collapsing glomerulopathy and mitochondrial impairment. The SARS-CoV-2-driven dysregulation of the immune responses including cytokine storm, macrophage activation syndrome, and lymphopenia can be other causes of the AKI. Organ interactions, endothelial dysfunction, hypercoagulability, rhabdomyolysis, and sepsis are other potential mechanisms of AKI. Moreover, lower oxygen delivery to kidney may cause an ischaemic injury. Understanding the fundamental molecular pathways and pathophysiology of kidney injury and AKI in Covid-19 is necessary to develop management strategies and design effective therapies.

The Role of Cytokines in Nephrotic Syndrome.

Idiopathic nephrotic syndrome (INS) is an important primary glomerular disease characterized by severe proteinuria. Evidence supports a role for T cell dysfunction in the pathogenesis of INS. Glucocorticoids are the primary therapy for INS; however, steroid-resistant NS (SRNS) patients are at a higher risk of drug-induced side effects and harbor poor prognosis. Although the exact mechanism of the resistance is unknown, the imbalances of T helper subtype 1 (Th1), Th2, and regulatory T cells (Tregs) and their cytokines may be involved in the pathogenesis of glucocorticoid responsiveness. Up to now, no confirmed biomarkers have been able to predict SRNS; however, a panel of cytokines may predict responsiveness and identify SRNS patients. Thus, the introduction of distinctive cytokines as novel biomarkers of SRNS enables both preventions of drug-related toxicity and earlier switch to more effective therapies. This review highlights the impacts of T cell population imbalances and their downstream cytokines on response to glucocorticoid responsiveness state in INS.

Curcumin nanoformulations: Beneficial nanomedicine against cancer.

Curcumin is a phytochemical achieved from the plant turmeric. It is extensively utilized for the treatment of several types of diseases such as cancers. Nevertheless, its efficiency has been limited because of rapid metabolism, low bioavailability, poor water solubility, and systemic elimination. Scientists have tried to solve these problems by exploring novel drug delivery systems such as lipid-based nanoparticles (NPs) (e.g., solid lipid NPs, nanostructured lipid carriers, and liposomes), polymeric NPs, micelles, nanogels, cyclodextrin, gold, and mesoporous silica NPs. Among these, liposomes have been the most expansively studied. This review mainly focuses on the different curcumin nanoformulations and their use in cancer therapy in vitro, in vivo, and clinical studies. Despite the development of curcumin-containing NPs for the treatment of cancer, potentially serious side effects, including interactions with other drugs, some toxicity aspects of NPs may occur that require more high-quality investigations to firmly establish the clinical efficacy.

Therapeutic benefits of rutin and its nanoformulations.

BACKGROUND: Rutin as a natural flavonoid compound has revealed an extensive range of therapeutic potentials. PURPOSE: The current paper is focused on the numerous studies on rutin nanoformulations regarding its broad spectrum of therapeutic potentials. STUDY AND METHODS: A review was conducted in electronic databases (PubMed) to identify relevant published literature in English. No restrictions on publication date were imposed. RESULTS: The literature search provided 7,078 results for rutin. Among them, 25 papers were related to the potential biological activities of rutin nanoformulations. Polymeric nanoparticles were the most studied nanoformulations for rutin (14 titles) and lipid nanoparticles (5 titles) were in second place. The reviewed literature showed that rutin has been used as an antimicrobial, antifungal, and anti-allergic agent. Improving the bioavailability of rutin using novel drug-delivery methods will help the investigators to use its useful effects in the treatment of various chronic human diseases. CONCLUSION: It can be concluded that the preparation of rutin nanomaterials for the various therapeutic objects confirmed the enhanced aqueous solubility as well as enhanced efficacy compared to conventional delivery of rutin. However, more investigations should be conducted to confirm the improved bioavailability of the rutin nanoformulations.

The Use of Infrapatellar Fat Pad-Derived Mesenchymal Stem Cells in Articular Cartilage Regeneration: A Review.

Cartilage is frequently damaged with a limited capacity for repair. Current treatment strategies are insufficient as they form fibrocartilage as opposed to hyaline cartilage, and do not prevent the progression of degenerative changes. There is increasing interest in the use of autologous mesenchymal stem cells (MSC) for tissue regeneration. MSCs that are used to treat articular cartilage defects must not only present a robust cartilaginous production capacity, but they also must not cause morbidity at the harvest site. In addition, they should be easy to isolate from the tissue and expand in culture without terminal differentiation. The source of MSCs is one of the most important factors that may affect treatment. The infrapatellar fat pad (IPFP) acts as an important reservoir for MSC and is located in the anterior compartment of the knee joint in the extra-synovial area. The IPFP is a rich source of MSCs, and in this review, we discuss studies that demonstrate that these cells have shown many advantages over other tissues in terms of ease of isolation, expansion, and chondrogenic differentiation. Future studies in articular cartilage repair strategies and suitable extraction as well as cell culture methods will extend the therapeutical application of IPFP-derived MSCs into additional orthopedic fields, such as osteoarthritis. This review provides the latest research concerning the use of IPFP-derived MSCs in the treatment of articular cartilage damage, providing critical information for the field to grow.

Pre-Eclampsia: Microbiota possibly playing a role.

Pre-eclampsia (PE) is a complication of pregnancy that is associated with mortality and morbidity in mothers and fetuses worldwide. Oxygen dysregulation in the placenta, abnormal remodeling of the spiral artery, defective placentation, oxidative stress at the fetal-maternal border, inflammation and angiogenic impairment in the maternal circulation are the main causes of this syndrome. These events result in a systemic and diffuse endothelial cell dysfunction, an essential pathophysiological feature of PE. The impact of bacteria on the multifactorial pathway of PE is the recent focus of scientific inquiry since microbes may cause each of the aforementioned features. Microbes and their derivatives by producing antigens and other inflammatory factors may trigger infection and inflammatory responses. A mother's bacterial communities in the oral cavity, gut, vagina, cervix and uterine along with the placenta and amniotic fluid microbiota may be involved in the development of PE. Here, we review the mechanistic and pathogenic role of bacteria in the development of PE. Then, we highlight the impact of alterations in a set of maternal microbiota (dysbiosis) on the pathogenesis of PE.

Effects of quercetin loaded nanostructured lipid carriers on the paraquat-induced toxicity in human lymphocytes.

Paraquat (PQ) as a herbicide and an environmental pollutant with increasing importance due to its toxicity to humans and animals. This study aimed to evaluate the protective and antioxidant activity of quercetin loaded Nanostructured Lipid Carriers (QNLC) against toxicity induced by PQ. Blood lymphocytes were prepared using Ficoll polysaccharide and subsequently by gradient centrifugation. The QNLC was prepared using an ultra-sonication method, which was characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The viability, reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), lysosome membrane integrity, Bax and Bcl2 gene expression were evaluated in human isolated lymphocytes. The results showed spherical QNLCs with nano-size range (52.7 nm) and high drug encapsulation efficiency (98.5% -96%). The results also indicated that PQ induced cell death, as well as ROS production, decreased by QNLC in human lymphocytes. Also, QNLC meaningfully restored MMP reduction, lysosomal membrane destabilization, and lipid peroxidation and were capable of preventing PQ-treated change in Bax and Bcl2 gene expression. We report that QNLC, have a significantly higher capacity to prevent PQ-induced toxicity than Q itself. It is suggested that the QNLC is a promising antioxidant for drug delivery to be used as a therapeutic and prophylactic agent for PQ poisoning.

The Use of Nanomaterials in Tissue Engineering for Cartilage Regeneration; Current Approaches and Future Perspectives.

The repair and regeneration of articular cartilage represent important challenges for orthopedic investigators and surgeons worldwide due to its avascular, aneural structure, cellular arrangement, and dense extracellular structure. Although abundant efforts have been paid to provide tissue-engineered grafts, the use of therapeutically cell-based options for repairing cartilage remains unsolved in the clinic. Merging a clinical perspective with recent progress in nanotechnology can be helpful for developing efficient cartilage replacements. Nanomaterials, < 100 nm structural elements, can control different properties of materials by collecting them at nanometric sizes. The integration of nanomaterials holds promise in developing scaffolds that better simulate the extracellular matrix (ECM) environment of cartilage to enhance the interaction of scaffold with the cells and improve the functionality of the engineered-tissue construct. This technology not only can be used for the healing of focal defects but can also be used for extensive osteoarthritic degenerative alterations in the joint. In this review paper, we will emphasize the recent investigations of articular cartilage repair/regeneration via biomaterials. Also, the application of novel technologies and materials is discussed.

Stem Cell Therapy: Curcumin Does the Trick.

Curcumin is a dietary polyphenol and a bioactive phytochemical agent that possesses anti-inflammatory, antioxidant, anticancer, and chemopreventive properties. Some of the predominant activities of stem cells include regeneration of identical cells and the ability to maintain the proliferation and multipotentiality. However, these cells could be stimulated to differentiate into specific cell types. Curcumin protects some stem cells from toxicity and can stimulate proliferation and differentiation of stem cells. In the present review, we summarize the antioxidant, stemness activity, antiaging, and neuroprotective as well as wound healing and regenerative effects of curcumin.

A review on potential toxicity of dental material and screening their biocompatibility.

OBJECTIVES: A wide range of compounds are utilized in dentistry such as dental composites, resins, and implants. The successful clinical use of dental materials relies on theirm physiochemical properties as well as biological and toxicological reliability. Different local and systemic toxicities of dental materials have been reported. Placement of these materials in oral cavity for a long time period might yield unwanted reactions. An extensive variety of materials is used in dentistry including filling materials, restorative materials, intracanal medicines, prosthetic materials, different types of implants, liners, and irrigants. The increasing rate in development of the novel materials with applications in the dental field has led to an increased consciousness of the biological risks and tempting restrictions of these materials. The biocompatibility of a biomaterial used for the replacement or filling of biological tissue such as teeth always had a high concern within the health care disciplines for patients. MATERIALS AND METHODS: Any material used in humans should be tested before clinical application. There are many tests evaluating biocompatibility of these materials at the point of in vitro, in vivo, and clinical investigations. RESULTS: The current review discusses the potential toxicity of dental material and screening of their biocompatibility. CLINICAL RELEVANCE: It is essential to use healthy and safe materials medical approaches. In dentistry, application of different materials in long-term oral usage demands low or nontoxic agents gains importance for both patients and the staff. Furthermore, screening tests should evaluate any potential toxicity before clinical application.

Betanin reduces organophosphate induced cytotoxicity in primary hepatocyte via an anti-oxidative and mitochondrial dependent pathway.

Organophosphates (OP) are potent pesticide commonly utilized in agricultural and domestic use. However, plentitude of data represent their side effects in different body tissues. We attempted to study whether betanin (a natural pigment) is able to mitigate some OPs-induced hepatotoxicity in primary rat hepatocytes. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) formation, lipid peroxidation (LPO), glutathione (GSH) depletion and mitochondrial depolarization were tested as toxicity markers. The outcomes revealed that betanin (25µM) significantly increased cell viability, plummeted ROS formation and LPO, restored cellular GSH reservoirs and protected mitochondria after chlorpyrifos (CPF) (300µM), diazinon (DZN) (600µM) and dichlrovos (DDVP) (400µM) treatment. Taken together, all data suggests the potential protective role of betanin in OPs-induced hepatotoxicity in which the mechanism appears to be inhibition of ROS formation and mitochondrial protection.

Protective effects of coenzyme Q10 nanoparticles on dichlorvos-induced hepatotoxicity and mitochondrial/lysosomal injury.

Development of biocompatible antioxidant nanoparticles for xenobiotic-induced liver disease treatment by oral or parenteral administration is of great interest in medicine. In the current study, we demonstrate the protective effects of coenzyme Q10 nanoparticles (CoQ10-NPs) on hepatotoxicity induced by dichlorvos (DDVP) as an organophosphate. Although CoQ10 is an efficient antioxidant, its poor bioavailability has limited the applications of this useful agent. First, CoQ10-NPs were prepared then characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). In DDVP-treated and non-treated hepatocytes in the presence of CoQ10-NPs, cell viability, the level of reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), lysosome membrane integrity, and cellular glutathione (GSH) content were measured. The prepared CoQ10-NPs were mono-dispersed and had narrow size distribution with average diameter of 54 nm. In the in vivo study, we evaluated the enzymes, which are involved in the antioxidant system for maintenance of normal liver function. In comparison to nonparticulate CoQ10, the CoQ10-NPs efficiently decreased the ROS formation, lipid peroxidation and cell death. Also, particulate form of CoQ10 improved MMP, GSH level and lysosome membrane integrity. In the in vivo, study, we revealed that CoQ10-NPs were better hepatoprotective than its nonparticulate form (P < .05). Altogether, we propose that the CoQ10-NPs have potential capability to be used as a therapeutic and prophylactic agent for poisoning that is induced by organophosphate agents, especially in the case of DDVP. Furthermore, these positive remarks make this nanoparticle amenable for the treatment of xenobiotic-induced liver diseases.

In vitro/vivo studies towards mechanisms of risperidone-induced oxidative stress and the protective role of coenzyme Q10 and N-acetylcysteine.

The hepatotoxic effects of the antipsychotic agent, risperidone (RIS) were investigated for better understanding the pathogenesis of RIS in liver toxicity in vivo and in in vitro. Isolated rat hepatocytes were obtained by collagenase perfusion technique and were then incubated with RIS, different antioxidants in particular coenzyme Q10 (CoQ10), N-acetyl cysteine (NAC). Our results showed that RIS could induce cytotoxicity via rising reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation. All of these effects were significantly (p < 0.05) inhibited by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate (ATP) generators. Similar outcomes were obtained from the in vivo experiments. Liver function enzyme test and histopathological evaluation confirmed RIS-(6 mg/kg) induced damage. Based on these results, it is suggested that RIS-induced liver toxicity is associated with mitochondrial/lysosomal cross-talk following the initiation of oxidative stress. Thus, the use of CoQ10 and/or NAC seems to be a safe therapeutic option in this context.

Cardiorenal syndrome: Plasmonic biosensors.

Cardiorenal syndrome (CRS) is defined as a broad spectrum of conditions encompassing both the heart and kidneys in which acute or chronic heart disorder may induce acute or chronic tubular injury in the kidneys and vice versa. Early diagnosis allows timely intervention and attenuates disease progression. Two well-established biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and brain (B-type) natriuretic peptide (BNP), are reflective of impaired cardiac and kidney function associated with poor prognosis in various cardiac disorders, including heart failure and coronary artery disease. Given the ongoing contribution of CRS to the high morbidity and mortality post-MI, early risk stratification and preventive measures are highly significant. In this review, we examine Surface Plasmon Resonance (SPR) optical biosensors for detection of these biomarkers and discuss potential implications of this highly sensitive and specific technology in CRS detection, treatment and outcomes.

Nanofiber scaffolds based on extracellular matrix for articular cartilage engineering: A perspective.

Articular cartilage has a low self-repair capacity due to the lack of vessels and nerves. In recent times, nanofiber scaffolds have been widely used for this purpose. The optimum nanofiber scaffold should stimulate new tissue's growth and mimic the articular cartilage nature. Furthermore, the characteristics of the scaffold should match those of the cellular matrix components of the native tissue to best merge with the target tissue. Therefore, selective modification of prefabricated scaffolds based on the structure of the repaired tissues is commonly conducted to promote restoring the tissue. A thorough analysis is required to find out the architectural features of scaffolds that are essential to make the treatment successful. The current review aims to target this challenge. The article highlights different optimization approaches of nanofibrous scaffolds for improved cartilage tissue engineering. In this context, the influence of the architecture of nanoscaffolds on performance is discussed in detail. Finally, based on the gathered information, a future outlook is provided to catalyze development in this promising field.

Natural and synthetic nanovectors for cancer therapy.

Nanomaterials have been extensively studied in cancer therapy as vectors that may improve drug delivery. Such vectors not only bring numerous advantages such as stability, biocompatibility, and cellular uptake but have also been shown to overcome some cancer-related resistances. Nanocarrier can deliver the drug more precisely to the specific organ while improving its pharmacokinetics, thereby avoiding secondary adverse effects on the not target tissue. Between these nanovectors, diverse material types can be discerned, such as liposomes, dendrimers, carbon nanostructures, nanoparticles, nanowires, etc., each of which offers different opportunities for cancer therapy. In this review, a broad spectrum of nanovectors is analyzed for application in multimodal cancer therapy and diagnostics in terms of mode of action and pharmacokinetics. Advantages and inconveniences of promising nanovectors, including gold nanostructures, SPIONs, semiconducting quantum dots, various nanostructures, phospholipid-based liposomes, dendrimers, polymeric micelles, extracellular and exome vesicles are summarized. The article is concluded with a future outlook on this promising field.

The Possible Association of IL-6R Gene Polymorphisms in the Development of Diabetic Nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a common complication of type 2 diabetes (T2D). Chronic inflammation and a combination of environmental and genetic factors are involved in the pathogenesis and development of DN. OBJECTIVE: This case-control study aimed to determine the relationship between rs7529229 and rs2228145 polymorphisms of the IL-6R gene with the incidence of nephropathy among T2D patients. METHODS: Fifty-six diabetic patients with nephropathy and 57 T2D patients without nephropathy were included based on inclusion criteria, along with 150 healthy individuals. METHODS: Fifty-six diabetic patients with nephropathy and 57 T2D patients without nephropathy were included based on inclusion criteria, along with 150 healthy individuals. RESULTS: The frequencies of AC and CC genotype distributions of the rs2228145 polymorphism in DN patients were significantly higher than in healthy individuals (24.1 and 9.3% versus 10.7 and 6.7%, respectively, P= 0.02). Moreover, the frequency of allele C was higher in DN patients compared to healthy controls (21.30% versus 12%, P=0.025). However, genotype distribution and allele frequencies of the rs7529229 IL-6R polymorphism in DN patients were not statistically significant in comparison with diabetic patients and healthy individuals (P> 0.05). CONCLUSION: The results showed that the allele and genotype distribution frequencies of rs2228145 IL-6R gene polymorphism in patients with DN were significantly higher than in healthy individuals. Therefore, the presence of this polymorphism may be involved in the development of diabetic nephropathy in this population.