Protective potential of naringenin and its nanoformulations in redox mechanisms of injury and disease.

Increasing evidence suggests that elevated intracellular levels of reactive oxygen species (ROS) play a significant role in the pathogenesis of many diseases. Increased intracellular levels of ROS can lead to the oxidation of lipids, DNA, and proteins, contributing to cellular damage. Hence, the maintenance of redox hemostasis is essential. Naringenin (NAR) is a flavonoid included in the flavanones subcategory. Various pharmacological actions have been ascribable to this phytochemical composition, including antioxidant, anti-inflammatory, antibacterial, antiviral, antitumor, antiadipogenic, neuro-, and cardio-protective activities. This review focused on the underlying mechanism responsible for the antioxidative stress properties of NAR and its' nanoformulations. Several lines of in vitro and in vivo investigations suggest the effects of NAR and its nanoformulation on their target cells via modulating signaling pathways. These nanoformulations include nanoemulsion, nanocarriers, solid lipid nanoparticles (SLN), and nanomicelle. This review also highlights several beneficial health effects of NAR nanoformulations on human diseases including brain disorders, cancer, rheumatoid arthritis, and small intestine injuries. Employing nanoformulation can improve the pharmacokinetic properties of NAR and consequently efficiency by reducing its limitations, such as low bioavailability. The protective effects of NAR and its' nanoformulations against oxidative stress may be linked to the modulation of Nrf2-heme oxygenase-1, NO/cGMP/potassium channel, COX-2, NF-κB, AMPK/SIRT3, PI3K/Akt/mTOR, BDNF, NOX, and LOX-1 pathways. Understanding the mechanism behind the protective effects of NAR can facilitate drug development for the treatment of oxidative stress-related disorders.

Detection of Coronavirus Disease 2019 (COVID-19) by TaqMan Real-Time PCR in Iran.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known as a positivesense single-strand RNA virus and leads to Coronavirus disease 2019 (COVID-19). Coronaviruses significantly impact the human respiratory tract. Coronavirus disease is potentially fatal and transmissible in the world. In this study we evaluated the presence or absence of SARS-CoV-2 in 220 patients with un-explained pneumonia by TaqMan real-time PCR assay regarding open reading frame (ORF1ab) and nucleocapsid (N) protein genes. Materials and methods: Totally, 224 patients entered the study. Upper and lower respiratory tract secretion samples were obtained during 2020 from patients. Samples contained nose and throat swabs with viral transport medium. RNA was isolated from clinical samples with the GenePure Plus fully automatic Nucleic Acid Purification System, NPA-32+ (Hangzhou Bioer Technology Co. Ltd, Hangzhou, China). Outcomes: 72.32% of cases were positive for COVID-19. All positive cases had the most common symptoms of illness regarding fatigue, dry cough, dyspnea, headache, abdominal pain, nausa, vomiting and myalgia. Fever was observed in 50% of positive cases. Chest computed tomography (CT) scan of all tested patients indicated two-sided chest involvement. Conclusion:Detection of COVID-19 by TaqMan real-time PCR seems to be a powerful method for the screening and detection of novel corona virus infection.

Enhanced wound-healing efficacy of electrospun mesoporous hydroxyapatite nanoparticle-loaded chitosan nanofiber developed using pluronic F127.

One of the goals of wound repairing is to mimic the function and architecture of the native extracellular matrix (ECM). To this end, for the first time, we used pluronic F127 and mesoporous rod-like hydroxyapatite nanoparticles (mr-HAP NPs) simultaneously to prepare a novel low-diameter electrospun ECM-mimicking wound dressing based on a mixture of chitosan and polyethylene oxide. F127 is used as a surface tension regulator of the polymer solution. In addition, F127 has the special ability to reduce the size of nanofibers. mr-HAP NPs are used as cell proliferation accelerators which also improve the mechanical properties and water uptake capacity of the as-prepared dressing. The average size of nanofibers in the presence of F127 was about 110 nm which was more than 2.5 times lower than nanofibers prepared without F127. The water uptake capacity was evaluated to investigate the wound exudate absorption capacity of the wound dressing. It was observed that the incorporation of mr-HAP NPs into wound dressing structure increases the water uptake capacity by more than 2.5 times. Alongside the evaluation of cytocompatibility through in vitro cell viability assay, the wound healing efficacy was also determined in full-thickness skin wounds in a rat model for 15 days. The cytocompatible wound dressing showed significantly higher wound closure efficacy than the control group so the wounds healed entirely on the last day of the treatment period. As well, the pathology analysis proved better granulation tissue development and greater re-epithelialization. These findings are by virtue of the improved mechanical properties, accelerated cell migration and proliferation, proper environment for oxygen exchange, and enhanced exudate uptake of the wound dressing. These all are due to the presence of F127 and mr-HAP.

Antioxidant Materials in Oral and Maxillofacial Tissue Regeneration: A Narrative Review of the Literature.

Oral and maxillofacial tissue defects caused by trauma, tumor reactions, congenital anomalies, ischemic diseases, infectious diseases, surgical resection, and odontogenic cysts present a formidable challenge for reconstruction. Tissue regeneration using functional biomaterials and cell therapy strategies has raised great concerns in the treatment of damaged tissue during the past few decades. However, during biomaterials implantation and cell transplantation, the production of excessive reactive oxygen species (ROS) may hinder tissue repair as it commonly causes severe tissue injuries leading to the cell damage. These products exist in form of oxidant molecules such as hydrogen peroxide, superoxide ions, hydroxyl radicals, and nitrogen oxide. These days, many scientists have focused on the application of ROS-scavenging components in the body during the tissue regeneration process. One of these scavenging components is antioxidants, which are beneficial materials for the treatment of damaged tissues and keeping tissues safe against free radicals. Antioxidants are divided into natural and synthetic sources. In the current review article, different antioxidant sources and their mechanism of action are discussed. The applications of antioxidants in the regeneration of oral and maxillofacial tissues, including hard tissues of cranial, alveolar bone, dental tissue, oral soft tissue (dental pulp, periodontal soft tissue), facial nerve, and cartilage tissues, are also highlighted in the following parts.

Curcumin-based nanoformulations alleviate wounds and related disorders: A comprehensive review.

Despite numerous advantages, curcumin's (CUR) low solubility and low bioavailability limit its employment as a free drug. CUR-incorporated nanoformulation enhances the bioavailability and angiogenesis, collagen deposition, fibroblast proliferation, reepithelization, collagen synthesis, neovascularization, and granulation tissue formation in different wounds. Designing nanoformulations with controlled-release properties ensure the presence of CUR in the defective area during treatment. Different nanoformulations encompassing nanofibers, nanoparticles (NPs), nanospray, nanoemulsion, nanosuspension, nanoliposome, nanovesicle, and nanomicelle were described in the present study comprehensively. Moreover, for some other systems which contain nano-CUR or CUR nanoformulations, including some nanofibers, films, composites, scaffolds, gel, and hydrogels seems the CUR-loaded NPs incorporation has better control of the sustained release, and thereby, the presence of CUR until the final stages of wound healing is more possible. Incorporating CUR-loaded chitosan NPs into nanofiber increased the release time, while 80% of CUR was released during 240 h (10 days). Therefore, this system can guarantee the presence of CUR during the entire healing period. Furthermore, porous structures such as sponges, aerogels, some hydrogels, and scaffolds disclosed promising performance. These architectures with interconnected pores can mimic the native extracellular matrix, thereby facilitating attachment and infiltration of cells at the wound site, besides maintaining a free flow of nutrients and oxygen within the three-dimensional structure essential for rapid and proper wound healing, as well as enhancing mechanical strength.

Acute and sub-acute toxicity assessment of the standardized extract of Sanguisorba minor in vivo.

Although Sanguisorba minor has been used as herbal medicine, no study has ever examined its potential toxicity. This study investigated acute and subacute toxicities of S. minor hydroalcoholic extract (SE). In the acute toxicity test, a single oral dose (300, 2,000, and 3,000 mg/kg) of SE was given to mice. The oral administration of SE (100, 200, and 400 mg/kg for 4 weeks) was performed to evaluate subacute toxicity. After the treatments, neurobehavioral, histopathology, hematological, and biochemical parameters were monitored. In vitro cytotoxicity was also assessed. Moreover, high-performance liquid chromatography fingerprint was done for the standardization of SE. The no-observed-adverse-effect level of SE was up to 2,000 mg/kg, and the LD50 of the prepared extract was over 3,000 mg/kg. The rats exposed to the extract did not show any marked change in their body weight. The extract at used doses did not affect neuromuscular coordination. According to the hematological, biochemical, and histological examinations, no significant treatment-related adverse effect of the extract was observed, even at 400 mg/kg. Only 48 h exposure to 400 µg/mL of SE reduced the viability of PC12 cells. The findings revealed that this plant could be well-tolerated, regarded safe, and used as herbal medicine.

Doped-carbon dots: Recent advances in their biosensing, bioimaging and therapy applications.

As a fascinating class of fluorescent carbon dots (CDs), doped-CDs are now sparked intense research interest, particularly in the diverse fields of biomedical applications due to their unique advantages, including low toxicity, physicochemical, photostability, excellent biocompatibility, and so on. In this review, we have summarized the most recent developments in the literature regarding the employment of doped-CDs for pharmaceutical and medical applications, which are published over approximately the past five years. Accordingly, we discuss the toxicity and optical properties of these nanomaterials. Beyond the presentation of successful examples of the application of these multifunctional nanoparticles in photothermal therapy, photodynamic therapy, and antibacterial activity, we further highlight their application in the cellular labeling, dual imaging, and in vitro and in vivo bioimaging by use of fluorescent-, photoacoustic-, magnetic-, and computed tomography (CT)-imaging. The potency of doped-CDs was also described in the biosensing of ions, small molecules, and drugs in biological samples or inside the cells. Finally, the advantages, disadvantages, and common limitations of doped-CD technologies are reviewed, along with the future prospects in biomedical research. Therefore, this review provides a concise insight into the current developments and challenges in the field of doped-CDs, especially for biological and biomedical researchers.

Silica-Quantum Dot Nanomaterials as a Versatile Sensing Platform.

Traditional analytical methods are bounded due to required high consumption of reagents, time, expensive equipment and complicated sample preparation. Thus, there is a demand for easy, fast and sensitive procedure to determine various analytes. In this regards, quantum dots (QDs) as fluorescent nanomaterials have attracted considerable attention due to their unique optical properties. Numerous studies have been reported regarding the application of QDs in sensor development for the detection of different analytes. Moreover, mesoporous silica nanoparticles which show ideal properties including biocompatibility, uniform pore size, stability in wide range of pH and an extremely high surface area could offer great opportunity in combination with QDs for the construction of sensing platforms. The fluorescent, chemiluminescent and electrochemical sensors based on silica-QDs materials could be used for the quantitative recognition of an extensive range of analytes like organic compounds, metal cations, toxic industrial compounds, drugs, and biogenic composites. In this review, we have summarized sensors based on combined QD-silica nanomaterials and their applications in the recognition of different analytes which are published over approximately the past five years.

Sensors design based on hybrid gold-silica nanostructures.

Hybrid silica-gold based sensors show attractive performance in sensing technologies. Due to their interesting optical properties and biological compatibility, gold nanoparticles (AuNPs) have been extensively implemented in sensing technology. Hybridization of AuNPs with silica NPs as a material with unique characteristic comprising large surface area, narrow pore distribution, tunable pore size and excellent charge transport provides great opportunity to fabricate promising sensing materials. This review summarizes the current developments on sensing devices based on gold-silica hybrid materials and discussing their interest in designing biosensors for improved analytes detection.

Folate conjugation improved uptake and targeting of porous hydroxyapatite nanoparticles containing epirubicin to cancer cells.

As hydroxyapatite (HAp) with the hexagonal crystal structure is biocompatible and bioactive. In the present study, HAp nanoparticles were synthesized and functionalized with polyethylene glycol and folic acid. The anticancer drug, epirubicin, was loaded to the folic acid-conjugated polyethylene glycol-coated HAp (FA-PEG-HAp) nanoparticles. The prepared nanoparticles were used for in vitro and in vivo experiments. Particle size analyzer showed that the hydrodynamic size of PEG-HAp and FA-PEG-HAp nanoparticles was 150.3 ± 1.5 nm and 217.2 ± 14.9 nm, respectively. The release behavior of epirubicin from nanoparticles showed an increase in the rate of release in acidic pH. The released drug in acidic pH was 2.5 fold more than pH 7.4. The results of in vitro study indicated an increase in cellular uptake of nanoparticles due to folate ligand. In vivo treatment with both PEG-HAp and FA-PEG-HAp nanoparticles had notably higher inhibition efficacy towards tumor growth than free epirubicin. In conclusion, folate conjugation provided higher uptake and better targeting of hydroxyapatite nanoparticles to cancer cells.

Enhanced gene delivery by polyethyleneimine coated mesoporous silica nanoparticles.

Due to large surface area, tunable pore size, easy surface manipulation, and low-toxicity mesoporous silica nanoparticles (MSNs) may act as a suitable vector for gene delivery. In order to make MSNs as a suitable gene delivery system, we modified the surface of phosphonated MSNs (PMSN) with polyethyleneimine (PEI) 10 and 25 KDa. Then nanoparticles were loaded with chloroquine (CQ) (a lysosomotropic agent) and complexed with plasmid DNA. The transfection efficiency and cytotoxicity of these nanoparticles was examined using green fluorescent protein plasmid (pGFP) and cytotoxicity assay. All PEI coated nanoparticles showed positive zeta potential and mean size was ranged between 170 and 215 nm with polydispersity index bellow 0.35. PEI-coated MSNs significiantly enhanced GFP gene expression in Neuro-2 A cells compared to PEI 10 and 25 KDa. The results of the cytotoxicity assays showed that these nanoparticles have an acceptable level of viability but CQ loaded nanoparticles showed higher cytotoxicity and lower transfection activity than CQ free nanoparticles.

Improved anticancer efficacy of epirubicin by magnetic mesoporous silica nanoparticles: in vitro and in vivo studies.

The development of magnetic nanoparticles as delivery carriers to magnetically accumulate anticancer drug in cancer tissue has attracted immense interest. In the present study, magnetic mesoporous silica nanoparticles (MMSNs) with magnetite core and silica shell were synthesized. The obtained MMSNs were characterized by DLS, XRD, FT-IR, TEM and VSM in order to investigate the nanoparticle characteristics. With the focus on in vivo validation of such magnetic drug delivery systems, we selected epirubicin (EPI) as the drug. The anticancer properties of EPI-loaded MMSNs were evaluated in a C-26 colon carcinoma model. Alongside monitoring of drug in the tissues with animal imaging system, the tissue distribution was also determined quantitavely. The average size of MMSNs determined with TEM images was about 18.68 ± 2.31 nm. The cellular uptake test indicated that geometric mean fluorescence intensity (MFI) of cells treated with MMSN + EPI in presence of external magnetic field was increasing 27% compared with free EPI. In addition, treatment with drug-loaded MMSNs with the aid of external magnetic gradient had significantly higher inhibition efficacy towards tumor growth than the free EPI treated mice. The targeted drug delivery through external magnet-attraction using EPI-loaded MMSNs resulted in high tumor cell uptake, which leads to elimination of cancer cells effectively.

Silica based hybrid materials for drug delivery and bioimaging.

Silica hybrid materials play an important role in improvement of novel progressive functional nanomaterials. Study in silica hybrid functional materials is supported by growing interest in providing intelligent materials that combine best of the inorganic silica structure along with organic or biological realms. Hybrid silica materials do not only provide fantastic opportunities for the design of novel materials for research but their represented unique properties open versatile applications specifically in nanomedicine since it was recognized by US FDA as a safe material for human trials. By combining various materials with different characteristics along with silica NPs as building blocks, silica-based hybrid vehicles were developed. In this regard, silica-based hybrid materials have shown great capabilities as unique carriers for bioimaging and/or drug delivery purposes. In the aforementioned hybrid systems, silica was preferred as a main building block of the hybrid structure, which is easily functionalized with different materials, bio-molecules and targeting ligands while providing biocompatibility for the system. This review will cover a full description of different hybrids of silica nanoparticles including silica-polymer, silica-protein, silica-peptide, silica-nucleic acid, silica-gold, silica-quantum dot, and silica-magnetic nanoparticles and their applications as therapeutic or imaging systems.

MUC1 aptamer-conjugated mesoporous silica nanoparticles effectively target breast cancer cells.

In the present study, we developed aptamer (Apt) conjugated mesoporous silica nanoparticles (MSNs) for specific delivery of epirubicin (EPI) to breast cancer cells. MSNs were synthesized and functionalized with 3-mercaptopropyltrimethoxysilane (3-MPTMS), followed by MUC1 aptamer conjugation through disulfide bonds. The nanoparticles were analyzed by transmission electron microscopy (TEM), particle size analyzer, zeta potential, elemental analysis (CHNS), aptamer conjugation efficiency, drug loading efficiency, and drug release profile. Cell uptake and in vitro cytotoxicity of different formulations were performed. The results of MSNs characterization confirmed spherical nanoparticles with thiol functional groups. Particle size of obtained nanoparticles was 163 nm in deionized water. After conjugation of MUC1 aptamer and EPI loading (MSN-MUC1-EPI), particle size increased to 258 nm. The aptamer conjugation to MSNs with disulfide bonds were confirmed using gel retardation assay. Cellular uptake studies revealed better cell uptake of MSN-MUC1-EPI compared to MSN-EPI. Moreover, cytotoxicity study results in MCF7 cell lines showed improved cytotoxicity of MSN-MUC1-EPI in comparison with MSN-EPI or EPI at the same concentration of drug. These results exhibited that MSN-MUC1-EPI has the potential for targeted drug delivery into MUC1 positive breast cancer cells to improve drug efficacy and alleviate side effects.

Magnetic silica nanocomposites for magnetic hyperthermia applications.

This article summarises nearly all magnetic silica nanocomposites that have been synthesised for biomedical applications and evaluated under alternating magnetic field (AMF) from the point of view of heat generation. The use of these nanocomposites as a drug delivery system for remote control of drug release via applying AMF is described. Different parameters that affect the magnetic properties and, therefore, affect the amount of generated heat and the fact that sometimes these parameters are in conflict with each other are discussed. This review article presents insight into the synthesis of nanocomposites with optimal characteristics and use of them in optimal conditions to achieve the optimal magnetic properties for magnetic hyperthermia.

Codelivery of anticancer drugs and siRNA by mesoporous silica nanoparticles.

The most common method for cancer treatment is chemotherapy. Multidrug resistance (MDR) is one of the major obstacles in chemotherapeutic treatment of many human cancers. One strategy to overcome this challenge is the delivery of anticancer drugs and siRNA simultaneously using nanoparticles. Mesoporous silica nanoparticles are one of the most popular nanoparticles for cargo delivery because of their intrinsic porosity. This paper highlights recent advances in codelivery of chemotherapeutic and siRNA with mesoporous silica nanoparticles for cancer therapy. In addition, synthesis and functionalization approaches of these nanoparticles are summarized. This review presents insight into the utilization of nanoparticles and combination therapy to achieve more promising results in chemotherapy.