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This study evaluated albendazole (ABZ) nanostructured lipid carriers (NLCs) for hepatocellular carcinoma treatment. ABZ-NLCs were prepared using emulsification-ultrasonication and optimised using a Box-Behnken design. Independent variables-lipids concentration (X 1 ), surfactant concentration (X 2 ), and sonication duration (X 3 )-were assessed for their effect on mean diameter (Y 1 ), PDI (Y 2 ), and entrapment efficiency (Y 3 ). The optimised formulation exhibited a mean diameter of 166.13 ± 3.72 nm, a PDI of 0.17 ± 0.01, a zeta potential of -39.86 ± 1.84 mV, an entrapment efficiency of 94.25 ± 6.12%, and a loading capacity of 99.93 ± 7.15 mg/g. Following chitosan coating (ABZ-CS-NLCs), all parameters were maintained, and the zeta potential developed to +24.61 ± 1.32 mV, improving cellular interaction. The cytotoxicity assays revealed that ABZ-CS-NLCs were more effective than uncoated NLCs and free ABZ, with an IC50 value of 8.89 μM in HepG2 cells. Overall, ABZ-CS-NLCs demonstrate a promising and effective delivery platform for targeted hepatic cancer therapy.

This study aims to highlight the potential use of cTNAs in therapeutic applications. The COVID-19 pandemic has led to significant use of coding therapeutic nucleic acids (cTNAs) in terms of DNA and mRNA in the development of vaccines. The use of cTNAs resulted in a paradigm shift in the therapeutic field. However, the injection of DNA or mRNA into the human body transforms cells into biological factories to produce the necessary proteins. Despite the success of cTNAs in the production of corona vaccines, they have several limitations such as instability, inability to cross biomembranes, immunogenicity, and the possibility of integration into the human genome. The chemical modification and utilization of smart drug delivery cargoes resolve cTNAs therapeutic problems. The success of cTNAs in corona vaccine production provides perspective for the eradication of influenza viruses, Zika virus, HIV, respiratory syncytial virus, Ebola virus, malaria, and future pandemics by quick vaccine design. Moreover, the progress cTNAs technology is promising for the development of therapy for genetic disease, cancer therapy, and currently incurable diseases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Catechin is a naturally occurring flavonoid of the flavan-3-ol subclass with numerous biological functions; however, these benefits are diminished due to several factors, including low water solubility and degradation in the stomach's harsh environment. So, this study aimed to develop an intelligent catechin colon-targeting delivery system with a high loading capacity. This was done by coating surface-decorated mesoporous silica nanoparticles with a pH-responsive enteric polymer called Eudragit®-S100. The pristine wormlike mesoporous silica nanoparticles (< 100 nm) with high surface area and large total pore volume were effectively synthesized and modified with the NH 2 group using the post-grafting strategy. Various parameters, including solvent polarity, catechin-carrier mass ratio, and adsorption time, were studied to improve the loading of catechin into the aminated silica nanoparticles. Next, the negatively charged Eudragit®-S100 was electrostatically coated onto the positively charged aminated nanocarriers to shield the loaded catechin from the acidic environment of the stomach (pH 1.9) and to facilitate site-specific delivery in the acidic environment of the colon (pH 7.4). The prepared nanomaterials were evaluated using several methods, including The Brauner-Emmett-Teller, surface area analyzer, zeta sizer, Field Emission Scanning Electron Microscope, Powder X-Ray Diffraction, Fourier Transform Infrared Spectroscopy, Energy-Dispersive X-ray Spectroscopy, and Differential Scanning Calorimetry. In vitro dissolution studies revealed that Eudragit®-S100-coated aminated nanomaterials prevented the burst release of the loaded catechin in the acidic environment, with approximately 90% of the catechin only being released at colonic pH (pH > 7) with a supercase II transport mechanism. As a result, silica nanoparticles coated with Eudragit®-S100 would provide an innovative and promising approach in targeted nanomedicine for the oral delivery of catechin and related medicines for treating diseases related to the colon, such as colorectal cancer and irritable bowel syndrome., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Gene editing technologies (GETs) could induce gene knockdown or gene knockout for biomedical applications. The clinical success of gene silence by RNAi therapies pays attention to other GETs as therapeutic approaches. This review aims to highlight GETs, categories, mechanisms, challenges, current use, and prospective applications. The different academic search engines, electronic databases, and bibliographies of selected articles were used in the preparation of this review with a focus on the fundamental considerations. The present results revealed that, among GETs, CRISPR/Cas9 has higher editing efficiency and targeting specificity compared to other GETs to insert, delete, modify, or replace the gene at a specific location in the host genome. Therefore, CRISPR/Cas9 is talented in the production of molecular, tissue, cell, and organ therapies. Consequently, GETs could be used in the discovery of innovative therapeutics for genetic diseases, pandemics, cancer, hopeless diseases, and organ failure. Specifically, GETs have been used to produce gene-modified animals to spare human organ failure. Genetically modified pigs are used in clinical trials as a source of heart, liver, kidneys, and lungs for xenotransplantation (XT) in humans. Viral, non-viral, and hybrid vectors have been utilized for the delivery of GETs with some limitations. Therefore, extracellular vesicles (EVs) are proposed as intelligent and future cargoes for GETs delivery in clinical applications. This study concluded that GETs are promising for the production of molecular, cellular, and organ therapies. The use of GETs as XT is still in the early stage as well and they have ethical and biosafety issues., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Bacterial infections caused by different strains of bacteria still one of the most important disorders affecting humans worldwide. Polymers nanocomposite systems could be considered as an alternative to conventional antibiotics to eradicate bacterial infections., Significance: In an attempt to enhance the antibacterial performance of silver and iron oxide nanoparticles, decrease their aggregation and toxicity, a polymeric hybrid nanocomposite system combining both nanoparticles is produced., Methods: Magnetic Ag-Fe 3 O 4 @polymer hybrid nanocomposites prepared using different polymers, namely polyethylene glycol 4000, ethyl cellulose, and chitosan were synthesized via wet impregnation and ball-milling techniques. The produced nanocomposites were tested for their physical properties and antibacterial activities., Results: XRD, FT-IR, VSM, and TEM results confirmed the successful preparation of hybrid nanocomposites. Hybrid nanocomposites have average crystallite sizes in the following order Ag-Fe 3 O 4 @CS (8.9 nm) < Ag-Fe 3 O 4 @EC (9.0 nm) < Ag-Fe 3 O 4 @PEG4000 (9.4 nm) and active surface area of this trend Ag-Fe 3 O 4 @CS (130.4 m 2 g -1 ) > Ag-Fe 3 O 4 @EC (128.9 m 2 g -1 ) > Ag-Fe 3 O 4 @PEG4000 (123.4 m 2 g -1 ). In addition, they have a saturation magnetization in this order: Ag-Fe 3 O 4 @PEG4000 (44.82 emu/g) > Ag-Fe 3 O 4 @EC (40.14 emu/g) > Ag-Fe 3 O 4 @CS (22.90 emu/g). Hybrid nanocomposites have a pronounced antibacterial action against Bacillus cereus, Escherichia coli , Pseudomonas aeruginosa , and Staphylococcus intermedius compared to iron oxide nanoparticles and positive antibacterial drug. In addition, both Ag-Fe 3 O 4 @EC and Ag-Fe 3 O 4 @CS have a lower MIC values compared to Ag-Fe 3 O 4 @PEG and positive control., Conclusion: Magnetic Ag-Fe 3 O 4 hybrid nanocomposites could be promising antibacterial nanomaterials and could pave the way for the development of new materials with even more unique properties and applications.

Background: Currently, the demands for restorations have increased considerably; thus, improvements and modifications have been made in dental composite technologies especially using materials that have been claimed to improve color stability., Objective: This study aimed to determine the effect of various solutions on the color stability of different restorative materials in vitro study., Methods: This study used three types of esthetic restorative materials. The samples comprised 45 discs, including 15 micro-hybrids, 15 nano-hybrids, and 15 glass ionomers). These discs were immersed in various beverages an hour a day for one month at room temperature. The color stability was measured using a spectrophotometer before/after immersion (days 7 and 30)., Results: We realized a significant difference in color change with Coca-Cola and tea-milk solution after seven days and 30 days (p < 0.05). However, no significant difference was found in the samples immersed in DM after seven days and 30 days (p > 0.05). The highest value of lightness (∆L) and stainability (∆a) was seen in micro-hybrid after 30 days of immersion in tea-milk solution (- 12.16 ± 1.74 and 11.4 ± 3.82, respectively), while most samples had a positive ∆b value., Conclusion: After one month, the tea-milk solution affected the color stability of all used restorative materials. In addition, micro-hybrid had higher color stability than nano-hybrid and glass ionomer., (© 2023. The Author(s).)

Tumor necrosis factor (TNF- α ) and inflammatory cytokine (IL-6) play a vital role in various cellular incidents such as the proliferation and death of cells during carcinogenesis. Hence, regulation of these biomarkers could be a promising tool for controlling tumor progression using nanoformulations. Silver nanoparticles-poly (vinyl pyrrolidone) (AgNPs-PVP) were prepared using the reduction of silver nitrate and stabilized with PVP. They are characterized through yield percentage, UV-VIS, FT-IR, size, charge, and morphology. The obtained AgNPs were tested for anticancer activity against prostate cancer (PC 3) and human skin fibroblast (HFS) cell lines. Moreover, biomarker-based confirmations like TNF- α and IL-6 were estimated. The synthesized AgNPs-PVP were stable, spherical in shape, with particle sizes of 122.33 ± 17.61 nm, a polydispersity index of 0.49 ± 0.07, and a negative surface charge of -19.23 ± 0.61 mV. In vitro cytotoxicity testing showed the AgNPs-PVP exhibited antiproliferation properties in PC3 in a dose-dependent manner. In addition, when compared to control cells, AgNPs-PVP has lower TNF- α with a significant value ( ∗ p < 0.05); the value reached 16.84 ± 0.71 pg/ml versus 20.81 ± 0.44 pg/ml, respectively. In addition, HSF cells showed a high level of reduction ( ∗∗∗ p < 0.001) in IL-6 production. This study suggested that AgNPs-PVP could be a possible therapeutic agent for human prostate cancer and anti-IL-6 in cancerous and noncancerous cells. Further studies will be performed to investigate the effect of AgNPs-PVP in different types of cancer., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Ahmed A. H. Abdellatif et al.)

Objective: Silver nanoparticles (AgNPs) are known to exhibit anti-inflammatory and anticancer activities. They have been reported to reduce the levels of tumor necrosis factor (TNF) - a proinflammatory cytokine involved in cell proliferation, differentiation, and apoptosis - in cell lines. As patients with breast cancer have been reported to have higher serum TNF levels, we aimed at developing a novel treatment for breast cancer by evaluating the effect of Trigonella foenum-graecum extract (TFG)-reduced AgNPs on the MCF-7 cell line, which serves as a model of human breast cancer., Materials and Methods: TFG-capped AgNPs were synthesized using a green reduction method, in which TFG reduced silver nitrate to generate AgNPs-TFG. The particle size, surface charge, ultraviolet (UV)-visible (VIS) spectra, surface morphology, % yield, and in vitro Ag+ release of the formulated AgNPs-TFG were evaluated. Additionally, the prepared NPs were examined for cytotoxicity using real-time polymerase chain reaction (real-time PCR), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and enzyme-linked immunosorbent assay (ELISA)., Results: The prepared AgNPs-TFG were uniform, small, discrete, and non-aggregated with a particle size of 22.5±0.75 nm and ζ-potential of -47.45±0.666 mV. The yield of AgNPs-TFG was 224.545±3.9 µM. Furthermore, the AgNP-TFG thin film exhibited a prolonged release of Ag+ in phosphate buffer for up to 11 h. AgNPs-TFG suppressed TNF-α expression at mRNA and protein levels in MCF-7 cells. Additionally, the formulated AgNPs-TFG did not exhibit any toxicity toward MCF-7 cells., Conclusions: This study showed that AgNP-TFG could effectively inhibit TNF-α. These results provide significant insights for developing new therapeutic strategies for cancer and other inflammatory illnesses.

Background: A thorough understanding of the original root and canal anatomy is a critical technical prerequisite for performing cleaning and shaping treatments. Therefore, this research aimed to characterize maxillary first premolar teeth' root morphology and canal architecture., Methods: One hundred forty-two extracted human adult maxillary first premolar teeth have been retrieved. The extracted teeth were thoroughly cleaned and irrigated to eliminate any remaining debris or blood. They were then preserved in formalin solution until they were eligible for screening. To begin, a visual examination was employed to ascertain the number of roots and their geometry in each sample. Then, utilizing digital radiography in two plains, mesiodistal and distomesial, to further determine those parameters. Finally, a sectioning technique had been used to have the samples cut mesiodistally into slices to validate the internal root canal architecture and identify the number of root canals and their varieties in accordance with Vertucci's categorization system. The canal layout, the pulp chamber, and the root canals were all highlighted (marked) using a fine tip marker in a permanent orange hue to make the canal features more accessible and accurate to visualize. All of the processes were conducted by two highly qualified dentists. The sample size was estimated statistically using the Sealed Envelope program, and the percentage of each configuration was derived in proportion to the overall sample size in order to establish the percentage of each type in each configuration., Results: From the 142 teeth examined, 42 (29.57%) had one root, 97 (68.31%) had two roots, and only three premolars (2.12%) had three roots. Concerning canal configurations, 100 teeth (70.43%) had type (IV) canal configuration, followed by 37 teeth (26.05%) had types (V), three teeth (2.12%) had type (VIII), and one tooth (0.70%) for each of type (I) and type (II)., Conclusions: The anatomical pattern of inspected maxillary first premolars are mainly two rooted and predominantly have a type (IV) canal morphology., (© 2022. The Author(s).)

The study aimed to develop a new glutathione (GSH) oral formulation to enhance the delivery of GSH and counter the nephrotoxicity of the anticancer drug, cyclophosphamide (CP). A nanostructured lipid carrier glutathione formulation (GSH-NLCs) composed of glutathione (500 mg), stearic and oleic acid (300 mg, each), and Tween ® 80 (2%, w / v ) was prepared through the emulsification-solvent-evaporation technique, which exhibited a 452.4 ± 33.19 nm spheroidal-sized particulate material with narrow particle size distributions, -38.5 ± 1.4 mV zeta potential, and an entrapment efficiency of 79.8 ± 1.9%. The GSH formulation was orally delivered, and biologically tested to ameliorate the CP-induced renal toxicity in a rat model. Detailed renal morphology, before and after the GSH-NLCs administration, including the histopathological examinations, confirmed the ameliorating effects of the prepared glutathione formulation together with its safe oral delivery. CP-induced oxidative stress, superoxide dismutase depletion, elevation of malondialdehyde levels, depletion of Bcl-2 concentration levels, and upregulated NF-KB levels were observed and were controlled within the recommended and near normal/control levels. Additionally, the inflammatory mediator marker, IL-1β, serum levels were marginally normalized by delivery of the GHS-NLCs formulation. Oral administration of the pure glutathione did not exhibit any ameliorating effects on the renal tissues, which suggested that the pure glutathione is reactive and is chemically transformed during the oral delivery, which affected its pharmacological action at the renal site. The protective effects of the GSH-NLCs formulation through its antioxidant and anti-inflammatory effects suggested its prominent role in containing CP-induced renal toxicity and renal tissue damage, together with the possibility of administrating higher doses of the anticancer drug, cyclophosphamide, to achieve higher and effective anticancer action in combination with the GSH-NLCs formulation.

The present study aimed to review major depression, including its types, epidemiology, association with different diseases status and treatments, as well as its correlation with the current COVID-19 pandemic. Mental depression is a common disorder that affects most individuals at one time or another. During depression, there are changes in mood and behavior, accompanied by feelings of defeat, hopelessness, or even suicidal thoughts. Depression has a direct or indirect relation with a number of other diseases including Alzheimer's disease, stroke, epilepsy, diabetes, cardiovascular disease and cancer. In addition, antidepressant drugs have several side effects including sedation, increased weight, indigestion, sexual dysfunction, or a decrease in blood pressure. Stopping medication may cause a relapse of the symptoms of depression and pose a risk of attempted suicide. The pandemic of COVID-19 has affected the mental health of individuals, including patients, individuals contacting patients and medical staff with a number of mental disorders that may adversely affect the immune ability of their bodies. Some of the drugs currently included in the protocols for treating COVID-19 may negatively affect the mental health of patients. Evidence accumulated over the years indicates that serotonin (5HT) deficiencies and norepinephrine (NE) in the brain can lead to mental depression. Drugs that increase levels of NE and 5HT are commonly used in the treatment of depression. The common reason for mood disorders, including mania and bipolar disease are not clearly understood. It is assumed that hyperactivity in specific parts of the brain and excessive activity of neurotransmitters may be involved. Early diagnosis and developing new treatment strategies are essential for the prevention of the severe consequences of depression. In addition, extensive research should be directed towards the investigation of the mental health disturbances occurring during and/or after COVID-19 infection. This may lead to the incorporation of a suitable antidepressant into the current treatment protocols.

Simvastatin (SV) repurposing has emerged as an alternative approach for the treatment of cancer. In this study, SV chitosan nanoparticles co-crosslinked with tripolyphosphate and chondroitin sulfate (SVCSChSNPs) were developed in order to maximize SV therapeutic efficiency. The hepatic targeting was realized using N-acetylgalactosamine (GalNAc) residues of ChS, which can be identified by the ASGPR receptors specifically expressed in hepatocytes. SV was repurposed as an anticancer agent against hepatocellular carcinoma (HCC). NPs were fabricated by the ionic gelation method, and the formulation variables (CS concentration, CS:ChS ratio, and CS solution pH) were optimized using a three-factor, three-level Box-Behnken design. The optimized NPs were investigated for particle size, size distribution, zeta potential, morphology, in vitro cytotoxicity, apoptotic effects against human hepatocellular carcinoma HepG2 cells, and detection of intracellular localization. The NPs were further evaluated for in vitro release behavior of SV and pharmacokinetics using Wister albino rats. Transmission electron microscopy (TEM) imaging showed a spherical shape with regular surface NPs of < 100 nm diameter. In vitro cytotoxicity testing showed that the SVCSChSNPs exhibited greater inhibition of proliferation in HepG2 cells and high cellular uptake through ASGPR-mediated endocytosis. The in vitro dissolution profile was 2.1-fold greater than that of pure SV suspension. Furthermore, in vivo oral pharmacokinetics revealed that the obtained NPs enhanced the bioavailability of SV by up to 2- and 1.6-fold for SV and SVA, respectively, compared to the pure SV suspension. These findings demonstrated that hepatic-targeted CSChSNPs delivering SV could potentially serve as a promising platform for HCC and other liver-related diseases., (© 2020 The Author(s).)

Intracellular compartment drug delivery is a promising strategy for the treatment of diseases. By this way, medicines can delivered to particular intracellular compartments. This maximizes the therapeutic efficacy and safety of medicines, particularly of anticancer and antiviral drugs. Intracellular compartment drug delivery is either indirectly by targeting of cell nucleus as central compartment of the cell or directly through the targeting of compartments itself. Drugs or nanoshuttles labeled with compartment's localization signal represent a smart tactic for subcellular compartment targeting. There are several boundaries prevent the arrival of shuttles to the specified intracellular compartments. These boundaries include selective permeability of biomembranes, efflux transporters, and lysosomes. The utilization of specific ligands during design of drug delivery nanoshuttles permits the targeting of specified intracellular compartment. Therefore drugs targeting could correct the diseases associated organelles. This review highlights the direct targeting of the medicines into subcellular compartment as a promising therapeutic strategy.