Systemic allergic contact dermatitis to palladium, platinum, and titanium: mechanisms, clinical manifestations, prevalence, and therapeutic approaches.

Contact dermatitis (CD) is an inflammatory skin disease of eczema that is elicited by chemicals or metal ions that have toxic effects without eliciting a T-cell response (contact elicitation) or by small reactive chemicals that modify proteins and induce innate and adaptive immune responses (contact allergens). The clinical condition is characterized by localized skin rash, pruritus, redness, swelling, and lesions, which are mainly detected by patch tests and lymphocyte stimulation. Heavy metals such as palladium (Pd), platinum (Pt), and titanium (Ti) are ubiquitous in our environment. These heavy metals have shown CD effects as allergic agents. Immunological responses result from the interaction of cytokines and T cells. Occupational metal CD accounts for most cases of work-related cutaneous disorders. In this systematic review, the allergic effects of heavy metals, including Pd, Pt, and Ti, and the mechanisms, clinical manifestations, prevalence, and therapeutic approaches are discussed in detail. Furthermore, the therapeutic approaches introduced to treat CD, including corticosteroids, topical calcineurin inhibitors, systemic immunosuppressive agents, phototherapy, and antihistamines, can be effective in the treatment of these diseases in the future. Ultimately, the insights identified could lead to improved therapeutic and diagnostic pathways.

Polyvinyl Alcohol (PVA)-Based Nanoniosome for Enhanced in vitro Delivery and Anticancer Activity of Thymol.

Introduction: There is an unmet need to develop potent therapeutics against cancer with minimal side effects and systemic toxicity. Thymol (TH) is an herbal medicine with anti-cancer properties that has been investigated scientifically. This study shows that TH induces apoptosis in cancerous cell lines such as MCF-7, AGS, and HepG2. Furthermore, this study reveals that TH can be encapsulated in a Polyvinyl alcohol (PVA)-coated niosome (Nio-TH/PVA) to enhance its stability and enable its controlled release as a model drug in the cancerous region. Materials and Methods: TH-loaded niosome (Nio-TH) was fabricated and optimized using Box-Behnken method and the size, polydispersity index (PDI) and entrapment efficiency (EE) were characterized by employing DLS, TEM and SEM, respectively. Additionally, in vitro drug release and kinetic studies were performed. Cytotoxicity, antiproliferative activity, and the mechanism were assessed by MTT assay, quantitative real-time PCR, flow cytometry, cell cycle, caspase activity evaluation, reactive oxygen species investigation, and cell migration assays. Results: This study demonstrated the exceptional stability of Nio-TH/PVA at 4 °C for two months and its pH-dependent release profile. It also showed its high toxicity on cancerous cell lines and high compatibility with HFF cells. It revealed the modulation of Caspase-3/Caspase-9, MMP-2/MMP-9 and Cyclin D/ Cyclin E genes by Nio-TH/PVA on the studied cell lines. It confirmed the induction of apoptosis by Nio-TH/PVA in flow cytometry, caspase activity, ROS level, and DAPI staining assays. It also verified the inhibition of metastasis by Nio-TH/PVA in migration assays. Conclusion: Overall, the results of this study revealed that Nio-TH/PVA may effectively transport hydrophobic drugs to cancer cells with a controlled-release profile to induce apoptosis while exhibiting no detectable side effects due to their biocompatibility with normal cells.

Chitosan-based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy.

Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS-based nanoparticles (CS-NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS-NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P-glycoprotein (P-gp) to reverse drug resistance. These nanoarchitectures can provide co-delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co-loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid-, carbon-, polymeric- and metal-based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS-NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS-NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH-sensitive release of DOX can occur. Furthermore, redox- and light-responsive CS-NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS-NPs, we expect to soon see significant progress towards clinical translation.

Nanobiotechnological approaches in anticoagulant therapy: The role of bioengineered silver and gold nanomaterials.

Nanotechnology is a novel area that has exhibited various remarkable applications, mostly in medicine and industry, due to the unique properties coming with the nanoscale size. One of the notable medical uses of nanomaterials (NMs) that attracted enormous attention recently is their significant anticoagulant activity, preventing or reducing coagulation of blood, decreasing the risk of strokes, heart attacks, and other serious conditions. Despite successful in vitro experiments, in vivo analyses are yet to be confirmed and further research is required to fully prove the safety and efficacy of nanoparticles (NPs) and to introduce them as valid alternatives to conventional ineffective anticoagulants with various shortcomings and side-effects. NMs can be synthesized through two main routes, i.e., the bottom-up route as a more preferable method, and the top-down route. In numerous studies, biological fabrication of NPs, especially metal NPs, is highly suggested given its eco-friendly approach, in which different resources can be employed such as plants, fungi, bacteria, and algae. This review discusses the green synthesis and characterization of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) as two of the most useful metal NPs, and also their alloys in different studies focussing on their anticoagulant potential. Challenges and alternative approaches to the use of these NPs as anticoagulants have also been highlighted.

Eco-friendly synthesis of carbon nanotubes and their cancer theranostic applications.

Carbon nanotubes (CNTs) with attractive physicochemical characteristics such as high surface area, mechanical strength, functionality, and electrical/thermal conductivity have been widely studied in different fields of science. However, the preparation of these nanostructures on a large scale is either expensive or sometimes ecologically unfriendly. In this context, plenty of studies have been conducted to discover innovative methods to fabricate CNTs in an eco-friendly and inexpensive manner. CNTs have been synthesized using various natural hydrocarbon precursors, including plant extracts (e.g., tea-tree extract), essential oils (e.g., eucalyptus and sunflower oil), biodiesel, milk, honey, and eggs, among others. Additionally, agricultural bio-wastes have been widely studied for synthesizing CNTs. Researchers should embrace the usage of natural and renewable precursors as well as greener methods to produce various types of CNTs in large quantities with the advantages of cost-effectiveness and environmentally benign features. In addition, multifunctionalized CNTs with improved biocompatibility and targeting features are promising candidates for cancer theranostic applications owing to their attractive optical, chemical, thermal, and electrical properties. This perspective discusses the recent developments in eco-friendly synthesis of CNTs using green chemistry-based techniques, natural renewable resources, and sustainable catalysts, with emphasis on important challenges and future perspectives and highlighting techniques for the functionalization or modification of CNTs. Significant and promising cancer theranostic applications as well as their biocompatibility and cytotoxicity issues are also discussed.

"Cutting the Mustard" with Induced Pluripotent Stem Cells: An Overview and Applications in Healthcare Paradigm.

Treatment of numerous ailments has been made accessible by the advent of genetic engineering, where the self-renewal property has unfolded the mysteries of regeneration, i.e., stem cells. This is narrowed down to pluripotency, the cell property of differentiating into other adult cells. The generation of induced pluripotent stem cells (iPSCs) was a major breakthrough in 2006, which was generated by a cocktail of 4 Yamanaka Factors, following which significant advancements have been reported in medical science and therapeutics. The iPSCs are reprogrammed from somatic cells, and the fascinating results focused on developing authentic techniques for their generation via molecular reprogramming mechanisms, with a plethora of molecules, like NANOG, miRNAs, and DNA modifying agents, etc. The iPSCs have exhibited reliable results in assessing the etiology and molecular mechanisms of diseases, followed by the development of possible treatments and the elimination of risks of immune rejection. The authors formulate a comprehensive review to develop a clear understanding of iPSC generation, their advantages and limitations, with potential challenges associated with their medical utility. In addition, a wide compendium of applications of iPSCs in regenerative medicine and disease modeling has been discussed, alongside bioengineering technologies for iPSC reprogramming, expansion, isolation, and differentiation. The manuscript aims to provide a holistic picture of the booming advancement of iPSC therapy, to attract the attention of global researchers, to investigate this versatile approach in treatment of multiple disorders, subsequently overcoming the challenges, in order to effectively expand its therapeutic window.

Nanobiotechnological prospects of probiotic microflora: Synthesis, mechanism, and applications.

Nanotechnology-driven solutions have almost touched every aspect of life, such as therapeutics, cosmetics, agriculture, and the environment. Physical and chemical methods for the synthesis of nanoparticles involve hazardous reaction conditions and toxic reducing as well as stabilizing agents. Hence, environmentally benign green routes are preferred to synthesize nanoparticles with tunable size and shape. Bacteria, fungi, algae, and medicinal plants are employed to synthesize gold, silver, copper, zinc, and other nanoparticles. However, very little literature is available on exploring probiotic bacteria for the synthesis of nanoparticles. In view of the background, this review gives the most comprehensive report on the nanobiotechnological potential of probiotic bacteria like Bacillus licheniformis, Bifidobacterium animalis, Brevibacterium linens, Lactobacillus acidophilus, Lactobacillus casei, and others for the synthesis of gold (AuNPs), selenium (SeNPs), silver (AgNPs), platinum (PtNPs), tellurium nanoparticles (TeNPs), zinc oxide (ZnONPs), copper oxide (CuONPs), iron oxide (Fe3O4NPs), and titanium oxide nanoparticles (TiO2NPs). Both intracellular and extracellular synthesis are involved as potential routes for biofabrication of polydispersed nanoparticles that are spherical, rod, or hexagonal in shape. Capsular exopolysaccharide associated carbohydrates such as galactose, glucose, mannose, and rhamnose, cell membrane-associated diglycosyldiacylglycerol (DGDG), 1,2-di-O-acyl-3-O-[O-α-D-galactopyranosyl-(1 → 2)-α-d-glucopyranosyl]glycerol, triglycosyl diacylglycerol (TGDG), NADH-dependent enzymes, amino acids such as cysteine, tyrosine, and tryptophan, S-layer proteins (SLP), lacto-N-triose, and lactic acid play a significant role in synthesis and stabilization of the nanoparticles. The biogenic nanoparticles can be recovered by rational treatment with sodium dodecyl sulfate (SDS) and/or sodium hydroxide (NaOH). Eventually, diverse applications like antibacterial, antifungal, anticancer, antioxidant, and other associated activities of the bacteriogenic nanoparticles are also elaborated. Being more biocompatible and effective, probiotic-generated nanoparticles can be explored as novel nutraceuticals for their ability to ensure sustained release and bioavailability of the loaded bioactive ingredients for diagnosis, targeted drug delivery, and therapy.

Bioengineering of green-synthesized silver nanoparticles: In vitro physicochemical, antibacterial, biofilm inhibitory, anticoagulant, and antioxidant performance.

Green-synthesized nanobiomaterials can be engineered as smart nanomedicine platforms for diagnostic and therapeutic purposes in medicine. Herein, we investigated the bioengineering of silver nanoparticles (AgNPs) and evaluated their physicochemical, antibacterial, biofilm inhibitory, anticoagulant, and antioxidant performance. Characterization of the AgNPs was performed utilizing UV-visible, transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray diffraction (XRD), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FT-IR). The spherical shaped AgNPs were proven by TEM and SEM techniques. Moreover, the XRD diffraction patterns demonstrated that the nanoparticles were in a crystalline state. The DLS represented the hydrodynamic particle size of the NPs at 49.62 nm at a pH of 9. The calculated minimum inhibitory concentration (MIC) of AgNPs toward Staphylococcus aureus (ATCC 25923) was 8 µg mL-1, which was almost similar to tetracycline by the value of 4 µg mL-1. Moreover, the minimum bactericidal concentration (MBC) of AgNPs was 64 µg mL-1, which was significantly less than the determined value of 256 µg mL-1 for tetracycline. Considering the pathogenic and standard S. aureus, the evaluated concentrations of AgNPs and tetracycline showed significant biofilm inhibitory performance. Furthermore, the bioengineered AgNPs exhibited significant anticoagulant activity at 500 µg mL-1 compared to saline (P < 0.001). In addition, the biogenic AgNPs inhibited 69.73 ± 0.56% of DPPH free radicals at 500 µg mL-1, indicating considerable antioxidant potential.

Calcium-based nanomaterials and their interrelation with chitosan: optimization for pCRISPR delivery.

There have been numerous advancements in the early diagnosis, detection, and treatment of genetic diseases. In this regard, CRISPR technology is promising to treat some types of genetic issues. In this study, the relationship between calcium (due to its considerable physicochemical properties) and chitosan (as a natural linear polysaccharide) was investigated and optimized for pCRISPR delivery. To achieve this, different forms of calcium, such as calcium nanoparticles (CaNPs), calcium phosphate (CaP), a binary blend of calcium and chitosan including CaNPs/Chitosan and CaP/Chitosan, as well as their tertiary blend including CaNPs-CaP/Chitosan, were prepared via both routine and green procedures using Salvia hispanica to reduce toxicity and increase nanoparticle stability (with a yield of 85%). Such materials were also applied to the human embryonic kidney (HEK-293) cell line for pCRISPR delivery. The results were optimized using different characterization techniques demonstrating acceptable binding with DNA (for both CaNPs/Chitosan and CaNPs-CaP/Chitosan) significantly enhancing green fluorescent protein (EGFP) (about 25% for CaP/Chitosan and more than 14% for CaNPs-CaP/Chitosan). Supplementary Information: The online version contains supplementary material available at 10.1007/s40097-021-00446-1.

Selenium Nanomaterials to Combat Antimicrobial Resistance.

The rise of antimicrobial resistance to antibiotics (AMR) as a healthcare crisis has led to a tremendous social and economic impact, whose damage poses a significant threat to future generations. Current treatments either are less effective or result in further acquired resistance. At the same time, several new antimicrobial discovery approaches are expensive, slow, and relatively poorly equipped for translation into the clinical world. Therefore, the use of nanomaterials is presented as a suitable solution. In particular, this review discusses selenium nanoparticles (SeNPs) as one of the most promising therapeutic agents based in the nanoscale to treat infections effectively. This work summarizes the latest advances in the synthesis of SeNPs and their progress as antimicrobial agents using traditional and biogenic approaches. While physiochemical methods produce consistent nanostructures, along with shortened processing procedures and potential for functionalization of designs, green or biogenic synthesis represents a quick, inexpensive, efficient, and eco-friendly approach with more promise for tunability and versatility. In the end, the clinical translation of SeNPs faces various obstacles, including uncertain in vivo safety profiles and mechanisms of action and unclear regulatory frameworks. Nonetheless, the promise possessed by these metalloid nanostructures, along with other nanoparticles in treating bacterial infections and slowing down the AMR crisis, are worth exploring.

Carbon Nanotubes: Smart Drug/Gene Delivery Carriers.

The unique properties of carbon nanotubes (CNTs) (such as their high surface to volume ratios, enhanced conductivity and strength, biocompatibility, ease of functionalization, optical properties, etc.) have led to their consideration to serve as novel drug and gene delivery carriers. CNTs are effectively taken up by many different cell types through several mechanisms. CNTs have acted as carriers of anticancer molecules (including docetaxel (DTX), doxorubicin (DOX), methotrexate (MTX), paclitaxel (PTX), and gemcitabine (GEM)), anti-inflammatory drugs, osteogenic dexamethasone (DEX) steroids, etc. In addition, the unique optical properties of CNTs have led to their use in a number of platforms for improved photo-therapy. Further, the easy surface functionalization of CNTs has prompted their use to deliver different genes, such as plasmid DNA (PDNA), micro-RNA (miRNA), and small interfering RNA (siRNA) as gene delivery vectors for various diseases such as cancers. However, despite all of these promises, the most important continuous concerns raised by scientists reside in CNT nanotoxicology and the environmental effects of CNTs, mostly because of their non-biodegradable state. Despite a lack of widespread FDA approval, CNTs have been studied for decades and plenty of in vivo and in vitro reports have been published, which are reviewed here. Lastly, this review covers the future research necessary for the field of CNT medicine to grow even further.

Current developments in green synthesis of metallic nanoparticles using plant extracts: a review.

Metal nanoparticles (MNPs) produced by green approaches have received global attention because of their physicochemical characteristics and their applications in the field of biotechnology. In recent years, the development of synthesizing NPs by plant extracts has become a major focus of researchers because of these NPs have low hazardous effect in the environment and low toxicity for the human body. Synthesized NPs from plants are not only more stable in terms of size and shape, also the yield of this method is higher than the other methods. Moreover, some of these MNPs have shown antimicrobial activity which is consistently confirmed in past few years. Plant extracts have been used as reducing agent and stabilizer of NPs in which we can reduce the toxicity in the environment as well as the human body only by not using chemical agents. Furthermore, the presence of some specific materials in plant extracts could be extremely helpful and effective for the human body; for instance, polyphenol, which may have antioxidant effects has the capability for capturing free radicals before they can react with other biomolecules and cause serious damages. In this article, we focused on of the most common plants which are regularly used to synthesize MNPs along with various methods for synthesizing MNPs from plant extracts.

Effects of vitamin A, C and E, or omega-3 fatty acid supplementation on the level of paraoxonase and arylesterase activity in streptozotocin-induced diabetic rats: an investigation of activities in plasma, and heart and liver homogenates.

INTRODUCTION: This study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus. METHODS: A total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured. RESULTS: Arylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors. CONCLUSION: Vitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications.

Protective role of calcium ion against stress-induced osmotic fragility of red blood cells in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus can increase osmotic fragility of red blood cells. Osmotic fragility test is an index of the function of cytoskeletal proteins and of the calcium pump activity in RBC membrane. The aim of this study is to determine the effect of physiological calcium supplement on red blood cell osmotic fragility of patients with type 2 diabetes mellitus. Osmotic fragility of red cells was determined for 30 healthy subjects and 30 patients in a NaCl gradient medium. 5 mg/dl of calcium was added to media and the osmotic fragility were evaluated for RBCs of patients and healthy subjects. Comparison of patients and control group showed higher sensitivity of red cells of patients to osmotic fragility upon exposure to higher sodium chloride concentrations. Comparison of initial, fifty percent and total hemolysis showed significant difference on initial and fifty percent hemolysis between two groups (P < 0.001). In healthy subjects, Fifty percent hemolysis index showed a smaller change after addition of calcium, from 4.1 ± 0.22 to 3.9 ± 0.2 (P < 0.05). Fifty percent hemolysis index for patients significantly decreased from 4.45 ± 0.17 to 4 ± 0.17 after addition of calcium (P < 0.001). Osmotic fragility increases in patients with diabetes. The role of calcium in cell membrane integrity was more prominent in the patients with diabetes than the healthy subjects, emphasizing the role of calcium on the membrane stability. We showed for the first time that controlling calcium ion concentration in patients with diabetes could exert a protective and beneficial role against membrane-affecting conditions.