Search

Backgrounds: The novel concept of microwave dynamic therapy (MDT) solves the problem of incomplete tumor eradication caused by non-selective heating and uneven temperature distribution of microwave thermal therapy (MWTT) in clinic, but the poor delivery of microwave sensitizer and the obstacle of tumor hypoxic microenvironment limit the effectiveness of MDT., Results: Herein, we engineer a liquid metal-based nanozyme LM@ZIF@HA (LZH) with eutectic Gallium Indium (EGaIn) as the core, which is coated with CoNi-bimetallic zeolite imidazole framework (ZIF) and hyaluronic acid (HA). The flexibility of the liquid metal and the targeting of HA enable the nanozyme to be effectively endocytosed by tumor cells, solving the problem of poor delivery of microwave sensitizers. Due to the catalase-like activity, the nanozyme catalyze excess H 2 O 2 in the tumor microenvironment to generate O 2 , alleviating the restriction of the tumor hypoxic microenvironment and promoting the production of ROS under microwave irradiation. In vitro cell experiments, the nanozyme has remarkable targeting effect, oxygen production capacity, and microwave dynamic effect, which effectively solves the defects of MDT. In the constructed patient-derived xenograft (PDX) model, the nanozyme achieves excellent MDT effect, despite the heterogeneity and complexity of the tumor model that is similar to the histological and pathological features of the patient. The tumor volume in the LZH + MW group is only about 1/20 of that in the control group, and the tumor inhibition rate is as high as 95%., Conclusion: The synthesized nanozyme effectively solves the defects of MDT, improves the targeted delivery of microwave sensitizers while regulating the hypoxic microenvironment of tumors, and achieves excellent MDT effect in the constructed PDX model, providing a new strategy for clinical cancer treatment., (© 2023. The Author(s).)

Trace elements and metals play critical roles in the normal functioning of the central nervous system (CNS), and their dysregulation has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In a healthy CNS, zinc, copper, iron, and manganese play vital roles as enzyme cofactors, supporting neurotransmission, cellular metabolism, and antioxidant defense. Imbalances in these trace elements can lead to oxidative stress, protein aggregation, and mitochondrial dysfunction, thereby contributing to neurodegeneration. In AD, copper and zinc imbalances are associated with amyloid-beta and tau pathology, impacting cognitive function. PD involves the disruption of iron and manganese levels, leading to oxidative damage and neuronal loss. Toxic metals, like lead and cadmium, impair synaptic transmission and exacerbate neuroinflammation, impacting CNS health. The role of aluminum in AD neurofibrillary tangle formation has also been noted. Understanding the roles of these elements in CNS health and disease might offer potential therapeutic targets for neurodegenerative disorders. The Codex Alimentarius standards concerning the mentioned metals in foods may be one of the key legal contributions to safeguarding public health. Further research is needed to fully comprehend these complex mechanisms and develop effective interventions.

Bacteria, similar to most organisms, have a love-hate relationship with metals: a specific metal may be essential for survival yet toxic in certain forms and concentrations. Metal ions have a long history of antimicrobial activity and have received increasing attention in recent years owing to the rise of antimicrobial resistance. The search for antibacterial agents now encompasses metal ions, nanoparticles and metal complexes with antimicrobial activity ('metalloantibiotics'). Although yet to be advanced to the clinic, metalloantibiotics are a vast and underexplored group of compounds that could lead to a much-needed new class of antibiotics. This Review summarizes recent developments in this growing field, focusing on advances in the development of metalloantibiotics, in particular, those for which the mechanism of action has been investigated. We also provide an overview of alternative uses of metal complexes to combat bacterial infections, including antimicrobial photodynamic therapy and radionuclide diagnosis of bacterial infections., (© 2023. Springer Nature Limited.)

Alzheimer's disease (AD), the most common form of neurodegeneration disorder in adults, is becoming the overwhelming burden on the healthcare and economic system. In this study, chrysin derivative with the morpholine moiety was designed, synthesized and evaluated based on the multi targets directed ligands strategy for the treatment of AD centered with therapeutic attempts to restore metal homeostasis. It selectively coordinated with the important bio-metal ions related AD, especially Cu 2+ . Notably, single crystals of both 1 and 1-Cu(II) were obtained and the single crystal structures were characterized by X-ray crystal diffraction, which provided a basis to further explore the possible structure-activity relationship at the molecular level. Compound 1 and 1-Cu(II) complex showed potent anti-oxidative activities, with respect to both ·OH and ·O 2 - scavenging properties In addition, 1 had good inhibitory activity on Aβ 1 - 42 aggregation, and it could target copper dyshomeostasis through extracting Cu 2+ from the amyloids. The studies in silico showed that 1 had brain availability and peroral bioavailability. Taken together, compound 1, as the derivative of chrysin, might be a promising advanced lead candidate for the development of new anti-AD drugs and it may provide a useful template for studying the structure-activity relationships of biometal-coordinating drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The slightest change in the extra/intracellular concentration of metal ions results in amplified effects by signaling cascades that regulate both cell fate within the tumor microenvironment and immune status, which influences the network of antitumor immunity through various pathways. Based on the fact that metal ions influence the fate of cancer cells and participate in both innate and adaptive immunity, they are widely applied in antitumor therapy as immune modulators. Moreover, nanomedicine possesses the advantage of precise delivery and responsive release, which can perfectly remedy the drawbacks of metal ions, such as low target selectivity and systematic toxicity, thus providing an ideal platform for metal ion application in cancer treatment. Emerging evidence has shown that immunotherapy applied with nanometallic materials may significantly enhance therapeutic efficacy. Here, we focus on the physiopathology of metal ions in tumorigenesis and discuss several breakthroughs regarding the use of nanometallic materials in antitumor immunotherapeutics. These findings demonstrate the prominence of metal ion-based nanomedicine in cancer therapy and prophylaxis, providing many new ideas for basic immunity research and clinical application. Consequently, we provide innovative insights into the comprehensive understanding of the application of metal ions combined with nanomedicine in cancer immunotherapy in the past few years., (© 2023. The Author(s).)

The neurodegenerative disorders are age-related illnesses that cause the morphology or activity of neurons to deteriorate over time. Alzheimer's disease is the most frequent neurodegenerative illness in the long run. The rate of advancement might vary, even though it is a progressive neurological illness. Various explanations have been proposed, however the true etiology of Alzheimer's disease remains unclear. Most pharmacological interventions are based on the cholinergic theory, that is earliest idea. In accordance with the amyloid hypothesis, the buildup of beta-amyloid in brain regions is the primitive cause of illness. There is no proof that any one strategy is useful in avoiding Alzheimer's disease, though some epidemiological studies have suggested links within various modifiable variables, such as cardiovascular risk, diet and so on. Different metals like zinc, iron, and copper are naturally present in our bodies. In metal chelation therapy drugs are used to jam the metal ions from combining with other molecules in the body. Clioquinol is one of the metal chelation drugs used by researchers. Research on metal chelation is still ongoing. In the present review, we go over the latest developments in prevalence, incidence, etiology, or pathophysiology of our understanding of Alzheimer's disease. Additionally, a brief discussion on the development of therapeutic chelating agents and their viability as Alzheimer's disease medication candidates is presented. We also assess the effect of clioquinol as a potential metal chelator., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Due to the urgent demand for more anti-cancer methods, the new applications of metal ions in cancer have attracted increasing attention. Especially the three kinds of the new mode of cell death, including ferroptosis, calcicoptosis, and cuproptosis, are of great concern. Meanwhile, many metal ions have been found to induce cell death through different approaches, such as interfering with osmotic pressure, triggering biocatalysis, activating immune pathways, and generating the prooxidant effect. Therefore, varieties of new strategies based on the above approaches have been studied and applied for anti-cancer applications. Moreover, many contrast agents based on metal ions have gradually become the core components of the bioimaging technologies, such as MRI, CT, and fluorescence imaging, which exhibit guiding significance for cancer diagnosis. Besides, the new nano-theranostic platforms based on metal ions have experimentally shown efficient response to endogenous and exogenous stimuli, which realizes simultaneous cancer therapy and diagnosis through a more controlled nano-system. However, most metal-based agents have still been in the early stages, and controlled clinical trials are necessary to confirm or not the current expectations. This article will focus on these new explorations based on metal ions, hoping to provide some theoretical support for more anti-cancer ideas., (© 2022. The Author(s).)

Transition metals refer to the elements in the d and ds blocks of the periodic table. Since the success of cisplatin and auranofin, transition metal-based compounds have become a prospective source for drug development, particularly in cancer treatment. In recent years, extensive studies have shown that numerous transition metal-based compounds could modulate autophagy, promising a new therapeutic strategy for metal-related diseases and the design of metal-based agents. Copper, zinc, and manganese, which are common components in physiological pathways, play important roles in the progression of cancer, neurodegenerative diseases, and cardiovascular diseases. Furthermore, enrichment of copper, zinc, or manganese can regulate autophagy. Thus, we summarized the current advances in elucidating the mechanisms of some metals/metal-based compounds and their functions in autophagy regulation, which is conducive to explore the intricate roles of autophagy and exploit novel therapeutic drugs for human diseases., (© 2021 Wiley Periodicals LLC.)

The current understanding of osteoarthritis is developing from a mechanical disease caused by cartilage wear to a complex biological response involving inflammation, oxidative stress and other aspects. Nanoparticles are widely used in drug delivery due to its good stability in vivo and cell uptake efficiency. In addition to the above advantages, metal/metal oxide NPs, such as cerium oxide and manganese dioxide, can also simulate the activity of antioxidant enzymes and catalyze the degradation of superoxide anions and hydrogen peroxide. Degrading of metal/metal oxide nanoparticles releases metal ions, which may slow down the progression of osteoarthritis by inhibiting inflammation, promoting cartilage repair and inhibiting cartilage ossification. In present review, we focused on recent research works concerning osteoarthritis treating with metal/metal oxide nanoparticles, and introduced some potential nanoparticles that may have therapeutic effects., (© 2021. The Author(s).)

Controlling spread of resistance genes from wastewater to aquatic systems requires more knowledge on how resistance genes are acquired and transmitted. Whole genomic sequences from sewage-associated staphylococcus isolates (20 S. aureus , 2 Staphylococcus warneri , and 2 Staphylococcus delphini ) were analyzed for the presence of antibiotic resistance genes (ARGs) and metal resistance genes (MRGs). Plasmid sequences were identified in each isolate to investigate co-carriage of ARGs and MRGs within. BLASTN analysis showed that 67% of the isolates carried more than one ARG. The carriage of multiple plasmids was observed more in CC5 than CC8 S. aureus strains. Plasmid exchange was observed in all staphylococcus species except the two S. delphini isolates that carried multiple MRGs, no ARGs, and no plasmids. 85% of S. aureus isolates carried the blaZ gene, 76% co-carried blaZ with cadD and cadX , with 62% of these isolates carrying blaZ , cadD , and cadX on the same plasmid. The co-carriage of ARGs and MRGs in S. warneri isolates, and carriage of MRGs in S. delphini , without plasmids suggests non-conjugative transmission routes for gene acquisition. More studies are required that focus on the transduction and transformation routes of transmission to prevent interspecies exchange of ARGs and MRGs in sewage-associated systems.

The levels of many essential minerals decrease during pregnancy if un-supplemented, including calcium, iron, magnesium, selenium, zinc, and possibly chromium and iodine. Sub-optimal intake of minerals from preconception through pregnancy increases the risk of many pregnancy complications and infant health problems. In the U.S., dietary intake of minerals is often below the Recommended Dietary Allowance (RDA), especially for iodine and magnesium, and 28% of women develop iron deficiency anemia during their third trimester. The goal of this paper is to propose evidence-based recommendations for the optimal level of prenatal supplementation for each mineral for most women in the United States. Overall, the evidence suggests that optimal mineral supplementation can significantly reduce a wide range of pregnancy complications (including anemia, gestational hypertension, gestational diabetes, hyperthyroidism, miscarriage, and pre-eclampsia) and infant health problems (including anemia, asthma/wheeze, autism, cerebral palsy, hypothyroidism, intellectual disability, low birth weight, neural tube defects, preterm birth, rickets, and wheeze). An evaluation of 180 commercial prenatal supplements found that they varied widely in mineral content, often contained only a subset of essential minerals, and the levels were often below our recommendations. Therefore, there is a need to establish recommendations on the optimal level of mineral supplementation during pregnancy., Competing Interests: JBA is the Chair of the Scientific Advisory Board of the Neurological Health Foundation (NHF), Chair of the NHF Task Force on Pregnancy-Safe Products, co-leader of the Scientific Advisory Board of the Autism Research Institute, member of the Scientific Advisory Board for an autism study of Finch Therapeutics, President of the Autism Nutrition Research Center, President of Autism Diagnostics, President of Autism Therapeutics, and President of the Autism Society of Greater Phoenix. He has received grant funding from the Department of Defense, Finch Therapeutics, Autism Research Institute, Autism Nutrition Research Center, and BHARE Foundation. He is a consultant for Finch Therapeutics and Healthy Nest, and in the latter case, he led the development of their prenatal supplement. He has patents/pending patents licensed to Finch Therapeutics and Autism Diagnostics.

It is widely recognized that innate macrophage immune reactions to implant debris are central to the inflammatory responses that drive biologic implant failure over the long term. Less common, adaptive lymphocyte immune reactions to implant debris, such as delayed type hypersensitivity (DTH), can also affect implant performance. It is unknown which key patient factors, if any, mediate these adaptive immune responses that potentiate particle/macrophage mediated osteolysis. The objective of this investigation was to determine to what degree known adaptive immune responses to metal implant debris can affect particle-induced osteolysis (PIO); and if this pathomechanism is dependent on: 1) innate immune danger signaling, i.e., NLRP3 inflammasome activity, 2) sex, and/or 3) age. We used an established murine calvaria model of PIO using male and female wild-type C57BL/6 vs. Caspase-1 deficient mice as well as young (12-16 weeks old) vs. aged (18-24 months old) female and male C57BL/6 mice. After induction of metal-DTH, and Cobalt-alloy particle (ASTM F-75, 0.4um median diameter) calvaria challenge, bone resorption was assessed using quantitative micro-computed tomography (micro-CT) analysis and immune responses were assessed by measuring paw inflammation, lymphocyte transformation test (LTT) reactivity and adaptive immune cytokines IFN-gamma and IL-17 (ELISA). Younger aged C57BL/6 female mice exhibited the highest rate and severity of metal sensitivity lymphocyte responses that also translated into higher PIO compared to any other experimental group. The absence of inflammasome/caspase-1 activity significantly suppressed DTH metal-reactivity and osteolysis in both male and female Caspase-1 deficient mice. These murine model results indicate that young female mice are more predisposed to metal-DTH augmented inflammatory responses to wear debris, which is highly influenced by active NLRP3 inflammasome/caspase-1 danger signaling. If these results are clinically meaningful for orthopedic patients, then younger female individuals should be appropriately assessed and followed for DTH derived peri-implant complications., Competing Interests: The authors have declared that no competing interests exist.

The bone regenerative capacity of synthetic calcium phosphates (CaPs) can be enhanced through the enrichment with selected metal trace ions. However, defining the optimal elemental composition required for bone formation is challenging due to many possible concentrations and combinations of these elements. We hypothesized that the ideal elemental composition exists in the inorganic phase of the bone extracellular matrix (ECM). To study our hypothesis, we first obtained natural hydroxyapatite through the calcination of bovine bone, which was then investigated its reactivity with acidic phosphates to produce CaP cements. Bioceramic scaffolds fabricated using these cements were assessed for their composition, properties, and in vivo regenerative performance and compared with controls. We found that natural hydroxyapatite could react with phosphoric acid to produce CaP cements with biomimetic trace metals. These cements present significantly superior in vivo bone regenerative performance compared with cements prepared using synthetic apatite. In summary, this study opens new avenues for further advancements in the field of CaP bone biomaterials by introducing a simple approach to develop biomimetic CaPs. This work also sheds light on the role of the inorganic phase of bone and its composition in defining the regenerative properties of natural bone xenografts., (© 2020 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

With the rapid advancement and progress of nanotechnology, nanomaterials with enzyme-like catalytic activity have fascinated the remarkable attention of researchers, due to their low cost, high operational stability, adjustable catalytic activity, and ease of recycling and reuse. Nanozymes can catalyze the same reactions as performed by enzymes in nature. In contrast the intrinsic shortcomings of natural enzymes such as high manufacturing cost, low operational stability, production complexity, harsh catalytic conditions and difficulties of recycling, did not limit their wide applications. The broad interest in enzymatic nanomaterial relies on their outstanding properties such as stability, high activity, and rigidity to harsh environments, long-term storage and easy preparation, which make them a convenient substitute instead of the native enzyme. These abilities make the nanozymes suitable for multiple applications in sensing and imaging, tissue engineering, environmental protection, satisfactory tumor diagnostic and therapeutic, because of distinguished properties compared with other artificial enzymes such as high biocompatibility, low toxicity, size dependent catalytic activities, large surface area for further bioconjugation or modification and also smart response to external stimuli. This review summarizes and highlights latest progress in applications of metal and metal oxide nanomaterials with enzyme/multienzyme mimicking activities. We cover the applications of sensing, cancer therapy, water treatment and anti-bacterial efficacy. We also put forward the current challenges and prospects in this research area, hoping to extension of this emerging field. In addition to therapeutic potential of nanozymes for disease prevention, their practical effects in diagnostics, to monitor the presence of SARS-CoV-2 and related biomarkers for future pandemics will be predicted.

An aging population leads to increasing demand for sustained quality of life with the aid of novel implants. Patients expect fast healing and few complications after surgery. Increased biofunctionality and antimicrobial behavior of implants, in combination with supportive stem cell therapy, can meet these expectations. Recent research in the field of bone implants and the implementation of autologous mesenchymal stem cells in the treatment of bone defects is outlined and evaluated in this review. The article highlights several advantages, limitations and advances for metal-, ceramic- and polymer-based implants and discusses the future need for high-throughput screening systems used in the evaluation of novel developed materials and stem cell therapies. Automated cell culture systems, microarray assays or microfluidic devices are required to efficiently analyze the increasing number of new materials and stem cell-assisted therapies. Approaches described in the literature to improve biocompatibility, biofunctionality and stem cell differentiation efficiencies of implants range from the design of drug-laden nanoparticles to chemical modification and the selection of materials that mimic the natural tissue. Combining suitable implants with mesenchymal stem cell treatment promises to shorten healing time and increase treatment success. Most research studies focus on creating antibacterial materials or modifying implants with antibacterial coatings in order to address the increasing number of complications after surgeries that are mostly caused by bacterial infections. Moreover, treatment of multiresistant pathogens will pose even bigger challenges in hospitals in the future, according to the World Health Organization (WHO). These antibacterial materials will help to reduce infections after surgery and the number of antibiotic treatments that contribute to the emergence of new multiresistant pathogens, whilst the antibacterial implants will help reduce the amount of antibiotics used in clinical treatment.

Therapy of malignant tumors is among the oldest and at the same time the most promising application areas of therapeutic metal complexes. The second part of our survey on metallopharmaceuticals deals with historical development and current state of coordination compounds in cancer therapy. It starts with the most famous and most successful metallodrug - cisplatin. After a brief account of the discovery of the anticancer properties of this substance follows the discussion of its chemical properties, toxicity, clinical application and resistance. Hereafter, complexes of other metals along with innovative research directions are addressed. The aim of this brief survey is to provide basic overview of the area of metallopharmacy, aimed at specialists in pharmacy and chemistry as well as at the general educated public.

Background and purpose - The use of trabecular metal cups in primary total hip arthroplasty (THA) is increasing, despite the survival of Continuum cups being slightly inferior compared with other uncemented cups in registries. This difference is mainly explained by a higher rate of dislocation revisions. Cup malpositioning is a risk factor for dislocation and, being made of a highly porous material, Continuum cups might be more difficult to position. We evaluated whether Continuum cups had worse cup positioning compared with other uncemented cups. Patients and methods - Based on power calculation, 150 Continuum cups from 1 center were propensity score matched with 150 other uncemented cups from 4 centers. All patients had an uncemented stem, femoral head size of 32 mm or 36 mm, and BMI between 19 and 35. All operations were done for primary osteoarthrosis through a posterior approach. Patients were matched using age, sex, and BMI. Cup positioning was measured from anteroposterior pelvic radiograph using the Martell Hip Analysis Suite software. Results - There was no clinically relevant difference in mean inclination angle between the study group and the control group (43° [95% CI 41-44] and 43° [CI 42-45], respectively). The study group had a larger mean anteversion angle compared with the control group, 19° (CI 18-20) and 17° (CI 15-18) respectively. Interpretation - Continuum cups had a greater anteversion compared with the other uncemented cups. However, the median anteversion was acceptable in both groups and this difference does not explain the larger dislocation rate in the Continuum cups observed in earlier studies.

Introduction: Although metallosis is a well-known complication after total hip arthroplasty, little is known about this phenomenon after total (TKA) or unicompartmental knee arthroplasty (UKA). The aim of the present work was to review the current knowledge about the reasons and the diagnostic as well as therapeutic management of metallosis after knee arthroplasty., Materials and Methods: A literature search was performed through PubMed until April 2019. Search terms were "metallosis" in combination with "knee", "knee prosthesis", "knee arthroplasty" and "knee replacement", respectively. All publications were analyzed regarding publication year, level of evidence, number of knees/patients treated, type of prosthesis, metallosis cause, time period between primary implantation and metallosis emergence, laboratory examination, treatment, complications and follow up., Results: A total of 38 studies reporting on a total of 97 knees were identified. 29 studies reported on metallosis after TKA, 8 after UKA, and one study after both procedures. The time period between the primary implantation and metallosis emergence ranged between 6 weeks and 26 years. The most common reason was the failure of a metal-backed patellar component in 40%, followed by implant/structural- and PE failure (wear/dislocation) in 27% and 18% of the cases, respectively. Complete blood cell count, serum chemistry, erythrocyte sedimentation rate or C-reactive protein serum values were not indicative to diagnose metallosis. The diagnosis was confirmed by histopathological analyses and macroscopic evaluation during surgery. Depending on the particular cause various surgical procedures have been performed. Complete prosthesis exchange was the most common one showing no complications in 89.4% of the cases., Conclusions: Metallosis after knee arthroplasty is a rare and perhaps underestimated or under published complication. A systematic diagnostic approach is necessary for the timely and correct diagnosis. A thorough debridement as well as a (sub)total synovectomy should be always performed. In cases with a damaged component, a partial/complete prosthesis exchange leads to the best results. Should a malalignment be the cause of the metallosis, then it should be corrected within the revision surgery.

Aims: Total knee arthroplasty is an established treatment for knee osteoarthritis with excellent long-term results, but there remains controversy about the role of uncemented prostheses. We present the long-term results of a randomized trial comparing an uncemented tantalum metal tibial component with a conventional cemented component of the same implant design., Methods: Patients under the age of 70 years with symptomatic osteoarthritis of the knee were randomized to receive either an uncemented tantalum metal tibial monoblock component or a standard cemented modular component. The mean age at time of recruitment to the study was 63 years (50 to 70), 46 (51.1%) knees were in male patients, and the mean body mass index was 30.4 kg/m 2 (21 to 36). The same cruciate retaining total knee system was used in both groups. All patients received an uncemented femoral component and no patients had their patella resurfaced. Patient outcomes were assessed preoperatively and postoperatively using the modified Oxford Knee Score, Knee Society Score, and 12-Item Short-Form Health Survey questionnaire (SF-12) score. Radiographs were analyzed using the American Knee Society Radiograph Evaluation score. Operative complications, reoperations, or revision surgery were recorded. A total of 90 knees were randomized and at last review 77 knees were assessed. In all, 11 patients had died and two were lost to follow-up., Results: At final review all patients were between 11 and 15 years following surgery. In total, 41 of the knees were cemented and 36 uncemented. There were no revisions in the cemented group and one revision in the uncemented group for fracture. The uncemented group reported better outcomes with both statistically and clinically significant (p = 0.001) improvements in knee-specific Oxford and Knee Society scores compared with the cemented group. The global SF-12 scores demonstrated no statistical difference (p = 0.812). Uncemented knees had better radiological analysis compared with the cemented group (p < 0.001)., Conclusion: Use of an uncemented trabecular metal tibial implant can afford better long-term clinical outcomes when compared to cemented tibial components of a matched design. However, both have excellent survivorship up to 15 years after implantation. Cite this article: Bone Joint J 2020;102-B(8):1025-1032.

Metallo-drugs have gained a huge attention among scientific community in the couple years. These drugs types have become important compounds in cancer therapy, where, for instance, platinum complexes are being used against many tumors worldwide. Nonetheless, to p-cymene metallo-derivatives a promising anticancer potential has also been increasingly proposed. In this sense, the present review aims to provide an in-depth revision of p-cymene metallo-drugs possible mechanisms of anticancer action for upcoming pharmaceutical and biotechnological prospects. p-cymene metallo-derivatives have revealed very interesting anticancer activities in various test systems, including cancer cells, being thus worth of note to deepen knowledge through clinical trials on their upcoming use for cancer chemotherapy combination.

Objective: To evaluate the efficacy of noble-metal coated catheters in reducing catheter-associated urinary tract infections (CAUTI) in adult patients requiring short term catheterization., Methods: An electronic literature search of PubMed, BioMed Central, Embase, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar was carried out from inception to 10th October 2019. Any prospective study or randomized controlled trial (RCT) on adult patients comparing noble-metal coated urinary catheters with any standard catheter and evaluating the incidence of CAUTI or bacteriuria was included., Results: A total of 13 studies were included in the systematic review. 12 were RCTs and one was a prospective cross-over trial. Catheters employed in the study group were grouped into two sub-groups: Silver alloy coated or Noble metal alloy-coated (Gold, Silver, and Palladium) catheters. Bacteriuria was the most commonly studied outcome variable across trials. Meta-analysis indicated that silver alloy-coated catheters (RR 0.63, 95%CI 0.44-0.90, P = 0.01; I2 = 72%) and noble metal alloy catheters (RR 0.58, 95%CI 0.41-0.81, P = 0.001; I2 = 0%) significantly reduce the risk of bacteriuria. Sub-group analysis based on the duration of catheterization demonstrated that silver alloy catheters reduce the risk of bacteriuria with >1week of catheterization (RR 0.46, 95%CI 0.26-0.81, P = 0.007; I2 = 63%). Symptomatic CAUTI was evaluated only in four studies with variable results. The quality of the included studies was not high., Conclusions: Our review indicates that bacteriuria may be reduced with the use of noble metal-coated catheters during short-term catheterization of adults, however, the quality of evidence is not high. It is not clear if these catheters reduce the risk of symptomatic CAUTI. Further homogenous RCTs are needed to provide clarity., Competing Interests: The authors have declared that no competing interests exist.

Liquid metals in recent years have grabbed the attention of researchers due to their expanded applicability not only in the field of therapeutics but also in theranostic. Acknowledged as a nuclear medicine due to its radioactivity, Gallium finds its widespread application in disorders of bone, calcium metabolism, and cancer. The present article deals with the advancement of gallium based nanoplatforms for therapy, imaging, and biosensing of cancers. The article describes the gallium based nanoconjugates and furnishes one's understanding of various therapeutic approaches such as photothermal therapy, sonodynamic therapy, radiotherapy, and immunotherapy along with various imaging platforms and biosensing platforms. A brief section related to patents on gallium based nanoplatforms in cancer has been included along with various molecular docking and simulation studies done on gallium. The recent advancement with respect to drug delivery gives an insight into the future perspective of gallium based nanoplatforms in the field of cancer theranostic., Competing Interests: Declaration of competing interest Authors report no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cichoric acid (CA) belongs to the group of polyphenols, which occurs in a variety of plant species and it is characterized by anticancer, antibacterial, and antiviral properties. Selected polyphenols have the ability to combine with metal ions to form chelate complexes that reveal greater biological activity than free compounds. In order to study possible antimicrobial and anticancer effect of CA and its complexes with copper(II)/zinc(II)/nickel(II)/cobalt(II) we decided to conduct cytotoxicity tests to estimate the most effective concentrations of tested compounds. The results of the presented study demonstrated, for the first time, that the treatment with newly synthesized CA-metal complexes has anticancer and antimicrobial effects, which were examined in seven different cell lines: MCF-7, MDA-MB-231, and ZR-75-1 breast cancer cell lines, A375 melanoma cell line, DLD-1 cell line, LN-229 cell line, FN cell line; five bacterial strains: Escherichia coli , Pseudomonas aeruginosa , Staphylococcus epidermidis , Proteus vulgaris, Lactobacillus rhamnosus , yeast Sacchcaromyces boulardii , and pathogenic yeast-like fungi Candida albicans . The presented study indicates that CA-metal complexes could be considered as a potential supplementary tool in anticancer therapy, however, because of their possible toxic activity on fibroblasts, they should be used with caution. Some of the tested complexes have also preservative properties and positive influence on normal non-pathogenic microorganisms, which was demonstrated in selected microbial strains, therefore they may serve as food preservatives of natural origin with cytoprotective properties.

Today, drug delivery systems based on nanostructures have become the most efficient to be studied. Recent studies revealed that the fullerenes can be used as drug carriers and transport drugs in a target cell. The aim of the present work is to study the interaction of C60 fullerene containing porphyrin-like transition metal-N4 clusters (TMN4C55, TM = Fe, Co, and Ni) with a non-steroidal anti-inflammatory drug (ibuprofen (Ibp)) by employing the method of the density functional theory. Results showed that the C60 fullerene with TMN4 clusters could significantly enhance the tendency of C60 for adsorption of ibuprofen drug. Also, our ultraviolet-visible results show that the electronic spectra of Ibp/TMN4C55 complexes exhibit a blue shift toward lower wavelengths (higher energies). It was found that the NiN4C55 fullerene had high chemical reactivity, which was important for binding of the drug onto the carrier surface. In order to gain insight into the binding features of Ibp/TMN4C55 complexes, the atoms in molecules analysis was also performed. Our results exhibit the electrostatic features of the Ibp/TMN4C55 bonding. Consequently, this study demonstrated that the TMN4C55 fullerenes could be used as potential carriers for delivery of Ibp drug in the nanomedicine domain. Graphical Abstract The TMN4C55 (TM=Fe, Co, and Ni) fullerenes could be used as potential carriers for delivery of ibuprofen drug in the nanomedicine domain.

Several metal-based phosphorus dendrimers were prepared. The first series developed by us was the Cu(II) series. In this series, the most potent is the third generation-Cu(II) showing original mechanism of action with activation of the pro-apoptotic Bax protein. To our knowledge, it is the first example of nanoparticles displaying Bax protein activation and then cell death through apoptosis process. Interestingly, this dendritic-Cu(II) complex showed synergistic effect with doxorubicin. Based on these interesting anti-proliferative activities, we developed Au(III)-conjugated phosphorus dendrimers. The most potent is the third generation-Au(III) dendrimer which represents also a new and promising first-in-class anti-proliferative agent against both solid and liquid tumor cell lines. Then, in order to analyze the influence of the metal moiety distribution of Cu(II) and Au(III) on the surface of dendrimers, mix Cu(II)-Au(III)-conjugated phosphorus dendrimers were also prepared and tested as anti-proliferative agents. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology., (© 2019 Wiley Periodicals, Inc.)

Metal wear debris and released ions (CoCrMo), which are widely generated in metal-on-metal bearings of hip implants, are also found in patients with metal-on-polyethylene bearings due to the mechanically assisted crevice corrosion of modular taper junctions, including head-neck and neck-stem taper interfaces. The resulting adverse reactions to metal debris and metal ions frequently lead to early arthroplasty revision surgery. National guidelines have since been published where the blood metal ion concentration of patients must consistently be monitored after joint replacement to prevent serious complications from developing after surgery. However, to date, the effect of metal particles and metal ions on local biological reactions is complex and still not understood in detail; the present study sought to elucidate the complex mechanism of metal wear-associated inflammation reactions. The knee joints in 4 groups each consisting of 10 female BALB/c mice received injections with cobalt chrome ions, cobalt chrome particles, and ultra-high-molecular-weight polyethylene (UHMWPE) particles or PBS (control). Seven days after injection, the synovial microcirculation and knee joint diameter were assessed via intravital fluorescence microscopy followed by histological evaluation of the synovial layer. Enlarged knee diameter, enhanced leukocyte to endothelial cell interactions, and an increase in functional capillary density within cobalt chrome particle-treated animals were significantly greater than those in the other treatment groups. Subsequently, pseudotumor-like tissue formations were observed only in the synovial tissue layer of the cobalt chrome particle-treated animals. Therefore, these findings strongly suggest that the cobalt chrome particles and not metal ions are the cause for in vivo postsurgery implantation inflammation., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Alexander C. Paulus et al.)

In this study, we report a metallogel developed based on metal-phenolic coordination of natural low-cost polyphenolic molecule and metal ions. Gelation occurs by mixing tannic acid (TA) and group (IV) titanium ions (Ti IV ) to form TA-Ti IV gel. The TA-Ti IV gel exhibits good capability to incorporate diverse metal ions by in situ co-gelation. Herein, five antimicrobial metal ions, i.e. ferric (Fe III ), copper (Cu II ), zinc (Zn II ), cobalt (Co II ) and nickel (Ni II ) ions, were employed to include in TA-Ti IV gels for developing intelligent dressings for infected wounds. The chemical and coordinative structures of TA-Ti IV metallogels were characterized by UV-Vis and Fourier-transform infrared (FT-IR) spectroscopies. Cytotoxicity of antimicrobial metallogels was explored by MTT assay with NIH 3T3 fibroblasts. The release of metal ions was evaluated by inductively coupled plasma mass spectrometry (ICP-MS), indicating the different releasing profiles upon the coordinative interactions of metal ions with TA. The formation and disassembly of metallogels are sensitive to the presence of acid and an oxidizer, H 2 O 2 , which are substances spontaneously generated in infected wounds due to the metabolic activity of bacteria and the intrinsic immune response. The Cu II releasing rates of TA-Ti IV -Cu II metallogels at different pH values of 5.5, 7.4 and 8.5 have been studied. In addition, addition of H 2 O 2 trigger fast release of Cu II as a result of oxidation of galloyl groups in TA. Consequently, the antimicrobial potency of TA-Ti IV -Cu II metallogels can be simultaneously activated while the wounds are infected and healing. The antimicrobial property of metallogels against Gram-negative Escherichia coli, and Gram-positive Methicillin-Resistant Staphylococcus aureus (USA300) and Staphylococcus epidermidis has been investigated by agar diffusion test. In an animal model, the TA-Ti IV -Cu II metallogels were applied as dressings for infected wounds, indicating faster recovery in the wound area and extremely lower amount of bacteria around the wounds, compared to TA-Ti IV gels and gauze. Accordingly, the intelligent nature derived metallogels is a promising and potential materials for medical applications.

The aim of this review is to make the reader familiar with currently available radiometals, their production modes, capacities, and quality concerns related to their medical use, as well as new emerging radiometals and irradiation technologies from the perspective of their diagnostic and theranostic applications. Production methods of 177 Lu serve as an example of various issues related to the production yield, specific activity, radionuclidic and chemical purity, and production economy. Other radiometals that are currently used or explored for potential medical applications, with particular focus on their theranostic value, are discussed. Using radiometals for diagnostic imaging and therapy is on the rise. The high demand for radiometals for medical use prompts investigations towards using alternative irradiation reactions, while using existing nuclear reactors and accelerator facilities. This review discusses these production capacities and what is necessary to cover the growing demand for theranostic nuclides., (© 2019 John Wiley & Sons, Ltd.)

Dental implants are often made of titanium alloys. Implant therapy currently promises a good long-term result without impacting health; however, its success depends on many factors. In this article, the authors focus on the most common risk factors associated with metallic surgical implants. Titanium-induced hypersensitivity can lead to symptoms of implant rejection. Corrosion and biofilm formation are additional situations in which these symptoms may occur. For medical purposes, it is important to define and discuss the characteristics of metals used in implantable devices and to ensure their biocompatibility. To avoid hypersensitivity reactions to metallic dental implants, precautionary principles for primary prevention should be established.

Objective: Hyperphosphatemia is a common complication in patients with end-stage renal disease on hemodialysis. The mainstay of phosphate management involves a low-phosphate diet and use of phosphate binders, yet these are often insufficient. This study was the first to use behavioral change techniques to encourage the use of phosphate binders and dietary modifications through a series of Phosphate Education and Planning (PEP) talks., Design and Methods: A total of 46 hemodialysis patients with hyperphosphatemia were enrolled. All patients were eligible to receive a series of 4 talks, each with defined goals of the long-term management of serum phosphate levels. Qualitative data from the talks were gathered during each intervention, whereas serum phosphate was selected as an outcome measure., Results: There was a modest improvement (-0.31 mg/dL) in the serum phosphate levels of the patients who received the entire PEP talk series. Furthermore, the most common self-identified barriers for patients were phosphate binder prescriptions not tailored to their eating routines and lack of resources for suitable dietary changes., Conclusions: The PEP talk series model is appropriate to manage persistent hyperphosphatemia despite usual management in outpatient dialysis unit by identifying patient-specific barriers and providing resources that can mitigate them. The strength of this model lies in using a multifaceted approach by applying both pharmacotherapy and dietary changes, along with behavioral change, to achieve lasting improvements in serum phosphate levels in hemodialysis patients with persistently elevated serum phosphate levels., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Although total hip arthroplasty is considered to be an effective surgical procedure for treating hip joint diseases, it is hindered by implant wear debris, which induces aseptic loosening. Various cell types are involved in this pathogenesis; however, the interactions between wear debris and osteoblasts, which serve a crucial role in bone formation, have not been clearly illustrated. In the present study, minor metallic wear particles were collected from the interfacial membrane around loosened implants of patients, and the biological effects of these particles on rat primary osteoblasts were then explored. The results demonstrated that metallic wear debris was able to induce the apoptosis of treated cells in a concentration‑ and time‑dependent manner. Furthermore, it was identified that reactive oxygen species (ROS) generation increased, the mitochondrial membrane potential collapsed, and the mitochondria‑caspase‑dependent and endoplasmic reticulum (ER) stress apoptotic pathways were activated following metallic wear debris application. In addition, apoptosis and associated pathways were inhibited by the use of N‑acetyl‑L‑cysteine, an antioxidant that suppresses ROS production, indicating that the ROS generation triggered ER stress, mitochondrial dysfunction and downstream cascades that contributed to cell apoptosis. These findings suggest that metallic wear debris‑induced ROS serve an important role in the apoptosis of osteoblasts. This provides a valuable insight, not only into understanding the mechanisms underlying the involvement of osteoblasts in osteolysis, but also into a potential novel therapeutic approach to treat implant aseptic loosening.

Platinum-based drugs have revolutionized cancer care, but are unfortunately associated with various adverse effects. Meanwhile, natural product scaffolds exhibit multifarious bioactivities and serve as an attractive resource for cancer therapy development. Thus, the conjugation of natural product scaffolds to metal complexes becomes an attractive strategy to reduce the severe side effects arising from the use of metal bearing drugs. This review aims to highlight the recent examples of natural product-conjugated metal complexes as cancer therapies with enhanced selectivity and efficacy. We discuss the mechanisms and features of different conjugate complexes and present an outlook and perspective for the future of this field.

Metal ions are indispensable for living organisms. However, the roles of metal ions in humans is complex, and remains poorly understood. Imbalances in metal ion levels, due to genetic or environmental sources, are associated with a number of significant health issues. However, in clinical medicine, the role of metal ions and metal-based drugs is notable in three major areas: as metal-related diseases; as metal-based medicines (including drugs, imaging agents, and metal chelators); and as agents of metal-based toxicity.

Purpose: To study the effect of a metal tracheal stent on radiation dose distribution., Method: A metal tube bracket is placed in a self-made foam tube sleeve, and micro-computed tomography scanning is performed directly. The foam sleeve containing the metal bracket is placed in a nonuniform phantom for a routine computed tomography scan. The stents in conventional computed tomography images are replaced by the stents in micro-computed tomography images. Subsequently, 2 sets of computed tomography images are obtained and then imported to a radiotherapy treatment planning system. A single photon beam at 0° is designed in a field size of 10 cm × 10 cm, a photon beam of 6 MV, and a monitor unit of 200 MU. Monte Carlo algorithm is used to calculate the dose distribution and obtain the dose curve of the central axis of the field. The dose is verified with thermoluminescence dose tablets., Results: The micro-computed tomography images of the tracheal stent are clearer and less false-like than its conventional computed tomography images. The planned dose curves of the 2 groups are similar. In comparison with the images without any stents in place, the doses at the incident surface of the stent in the conventional computed tomography images and at the stent exit surface in the rear of the stent increase by 1.86% and 2.76%, respectively. In the micro-computed tomography images, the doses at the incident surface of the stent and at the exit surface behind the stent increase by 1.32% and 1.19%, respectively. Conventional computed tomography reveals a large deviation between the measured and calculated values., Conclusion: Tracheal stent based on micro-computed tomography imaging has a less effect on radiotherapy calculation than that based on conventional computed tomography imaging.

Despite improvements in the 5-year survival rate to over 80% in cancers, such as Hodgkin lymphoma and testicular cancer, more aggressive tumors including pancreatic and brain cancer still have extremely low survival rates. The establishment of chemoresistance, responsible for the reduction in treatment efficiency and cancer relapse, is one possible explanation for this setback. Metal-based compounds, a class of anticancer drugs, are largely used in the treatment of cancer. Herein, we will review the use of metal-based small molecules in chemotherapy, focusing on recent studies, and we will discuss how new nonplatinum-based agents are prompting scientists to increase drug specificity to overcome chemoresistance in cancer cells.

Cancer is developed by rapid, uncontrolled, and abnormal cell proliferation and one of the leading causes of deaths worldwide in human beings. For the remedial measures of preventing different types of cancers, one of the research domains that have gained substantial importance in medical science is the development of new metallo-drugs and their investigations as potential anticancer drug agents by using various analytical techniques. Since metal-based complexes show weak absorption bands, electrochemical methods are considered more feasible and preferable over spectroscopic methods for easy characterization. Due to closer resemblance of electrochemical and biological processes, cyclic voltammetry among different electrochemical methods is considered the most versatile for the study of in-vitro metal-based drug-DNA interactions in terms of changes in the redox activities. Current potential data of a metal complex leads to determine binding kinetics in terms of binding constant and binding site size that involve determining the binding mode of drug with DNA, i.e., electrostatic interactions, intercalation, or minor-major groove binding. Binding parameters and modes of interactions, further, help to develop the mechanism of action of drug with the DNA. In this review, we emphasize on cyclic voltammetric DNA binding studies on some metal complexes that have been carried out in the last three decades for the investigation of their anticancer potentials.

Due to the increasing number of primary hip arthroplasty procedures, revision surgery will be an increasing challenge. The surgeon is frequently confronted with important acetabular defects. Careful preoperative planning is essential to achieve functional and long-term success. Treatment options include porous hemispheric cups, porous metal augments, oblong cups, cemented implants, rings, allografts, patient specific implants and component combinations. In addition to large hemispherical cups, modular porous metal revision systems are increasingly being used to treat severe acetabular bone loss. This article provides an overview of relevant literature and implant-specific features of different reconstruction strategies., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: The objective of this systematic review was to assess the influence of implant-abutment connection and abutment material on the outcome of implant-supported single crowns (SCs) and fixed dental prostheses (FDPs)., Methods: An electronic Medline search complemented by manual searching was conducted to identify randomized controlled clinical trials, prospective and retrospective studies with a mean follow-up time of at least 3 years. Patients had to have been examined clinically at the follow-up visit. Failure and complication rates were analyzed using robust Poisson regression, and comparisons were made with multivariable Poisson regression models., Results: The search provided 1511 titles and 177 abstracts. Full-text analysis was performed for 147 articles resulting in 60 studies meeting the inclusion criteria. Meta-analysis of these studies indicated an estimated 5-year survival rate of 97.6% for SCs and 97.0% for FDPs supported by implants with internal implant-abutment connection and 95.7% for SCs and 95.8% for FDPs supported by implants with external connection. The 5-year abutment failure rate ranged from 0.7% to 2.8% for different connections with no differences between the types of connections. The total number of complications was similar between the two connections, yet, at external connections, abutment or occlusal screw loosening was more predominant. Ceramic abutments, both internally and externally connected, demonstrated a significantly higher incidence of abutment fractures compared with metal abutments., Conclusion: For implant-supported SCs, both metal and ceramic abutments with internal and external connections exhibited high survival rates. Moreover, implant-supported FDPs with metal abutments with internal and external connections for also showed high survival rates., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The growing trends of total knee arthroplasty (TKA) foreshadow an inevitable increase in the financial burden on healthcare expenditure estimated to almost nine billion dollars annually. This study aims to demonstrate the potential savings when using all-polyethylene (AP) compared to metal-backed (MB) tibial components and describes the cost variability amongst three major commercially available implants., Materials and Methods: The cost of AP versus MB implants was analyzed using a large nationwide database, Emergency Care Research Institute (ECRI). Cost of femoral components and patellar buttons were excluded. The three manufacturers included in the study were DePuy, Smith&Nephew, and Stryker (Zimmer data was not available for analysis)., Results: Our results show that AP components were significantly less costly in comparison to other manufacturers, and the average AP price was $1,009. The average MB (baseplate plus liner) price was $2,054 (p<0.01). Analysis of variance (ANOVA) of the means of the AP components showed no significant difference in prices among the three studied manufacturers (p=0.946)., Discussion: Our results demonstrate that, regardless of the manufacturing company, AP tibial components are significantly cheaper than their MB counterparts. A literature review revealed that, when indicated, AP implants are not inferior to MB in terms of survivorship or outcome. The average savings was more than $1,000 per TKA when multiplied even by a small portion of the large volume of TKAs completed annually. This can translate into millions of dollars in savings in healthcare expenditures. With the impending legislation of the bundled-payment initiative, orthopaedic surgeons should be aware of less costly implant options that can positively impact outcomes and/or quality of care.

The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum . In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between new bone tissue formation and material degradation has not been found, until now. The addition of different substances such as collagen or growth factors and also of different cell types has already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are used differently as a basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue, playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designed for bone regeneration, with the aim to provide an overview of currently existing knowledge about the effects of metals in the field of bone regeneration., Competing Interests: The authors declare no conflict of interest.

Background: Although cisplatin and a number of platinum complexes have widely been used for the treatment of neoplasia, patients receiving these treatments have frequently suffered from their severe toxic side effects, the development of resistance with consequent relapse. In the recent decades, numerous complexes of coinage metals including that of gold, copper and silver have been reported to display promising in vitro and/or in vivo anti-cancer activities as well as potent activities towards cisplatin-resistant tumors. Nevertheless, the medical development of these metal complexes has been hampered by their instability in aqueous solutions and the nonspecific binding in biological systems., Methods: One of the approaches to overcome these problems is to design and develop adequate drug delivery systems (DDSs) for the transport of these complexes. By functionalization, encapsulation or formulation of the metal complexes, several types of DDSs have been reported to improve the desired pharmacological profile of the metal complexes, improving their overall stability, bioavailability, anti-cancer activity and reducing their toxicity towards normal cells., Conclusion: In this review, we summarized the recent findings for different DDSs for various anti- cancer active complexes of some coinage metals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

In the recent times, nanomaterials are used in many sectors of science, medicine and industry, without revealing its toxic effects. Thus, it is in urgent need for exploring the toxicity along with the application of such useful nanomaterials. Nanomaterials are categorized with a particle size of 1-100 nm. They have gained increasing attention because of their novel properties, including a large specific surface area and high reaction activity. The various fundamental and practical applications of nanomaterials include drug delivery, cell imaging, and cancer therapy. Nanosized semiconductors have their versatile applications in different areas such as catalysts, sensors, photoelectronic devices, highly functional and effective devices etc. Metal oxides contribute in many areas of chemistry, physics and materials science. Mechanism of toxicity of metal oxide nanoparticles can occur by different methods like oxidative stress, co-ordination effects, non-homeostasis effects, genotoxicity and others. Factors that affect the metal oxide nanoparticles were size, dissolution and exposure routes. This chapter will explain elaborately the toxicity of metal oxide nano structures in living beings and their effect in ecosystem.

Purpose: To evaluate the clinical efficacy of percutaneous trans-hepatic integrated 125I seed stents implantation for malignant lower biliary tract obstruction., Methods: Thirty-two patients with malignant lower biliary obstruction were randomly divided into two groups. One group underwent the therapy with integrated 125I seed stents (Test group, n = 13), and another group received conventional metal stents implantation for treatment (Control group, n = 19). The pre- and post-operative changes in biochemical indices, white blood cell count, IgG level, stent patency, survival time, tumor size and complications were compared between the two groups. RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) was used to evaluate therapeutic effects. The average follow-up time was 12.3 months., Results: The differences between pre- and post-operative (30 days) intragroup biochemical indices had statistically significant difference (P < 0.05), but there were no significant differences (P > 0.05) in leukocyte counts and IgG levels. As to the median time of stent patency and patients' survival, there were significant differences (P < 0.05) between Control and Test groups (3.9 months vs. 8.1 months, 139 days vs. 298 days, respectively). Three months after the operation, the average tumor size was reduced in the Test group, but was increased in the Control group (P < 0.05). There was no significant difference in the incidence of complications between the two groups. The evaluation results using RECIST 1.1 showed that there were statistically significant differences between the two groups in terms of the rates of remission, control, and progression (χ2 = 17.5, P < 0.05)., Conclusions: The study indicates that integrated 125I seed stents are effective in reducing jaundice symptoms, inhibiting tumor growth, improving stent patency and prolonging patient survival, which may serve as a safer and more feasible method in treating malignant lower biliary obstruction with minimal invasiveness.

This paper presents a novel stretchable pulse sensor fabricated by a selective liquid-metal plating process (SLMP), which can conveniently attach to the human skin and monitor the patient's heartbeat. The liquid metal-based stretchable pulse sensor consists of polydimethylsiloxane (PDMS) thin films and liquid metal functional circuits with electronic elements that are embedded into the PDMS substrate. In order to verify the utility of the fabrication process, various complex liquid-metal patterns are achieved by using the selective wetting behavior of the reduced liquid metal on the Cu patterns of the PDMS substrate. The smallest liquid-metal pattern is approximately 2 μm in width with a uniform surface. After verification, a transparent flowing LED light with programmed circuits is realized and exhibits stable mechanical and electrical properties under various deformations (bending, twisting and stretching). Finally, based on SLMP, a wireless pulse measurement system is developed which is composed of the liquid metal-based stretchable pulse sensor, a Bluetooth module, an Arduino development board, a laptop computer and a self-programmed visualized software program. The experimental results reveal that the portable non-invasive pulse sensor has the potential to reduce costs, simplify biomedical diagnostic procedures and help patients to improve their life in the future.

The targeting and delivery of therapeutic and diagnostic agents to bone tissue presents both a challenge and opportunity. Osteoporosis, Paget's disease, cancer, and bone metastases are all skeletal diseases whose treatment would benefit from new targeted therapeutic strategies. Osteoporosis, in particular, is a very prevalent disease, affecting over one in three women and one in five men in Canada alone with the cost to the healthcare system estimated at over $2.3 billion in 2010. Bone tissue is often considered a rigid structure when in reality there is a process of continuous remodeling that takes place via complex endocrine-regulated cell signaling pathways in addition to the signaling pathways unique to bone tissue. It is these specific boneremodeling processes that provide unique targeting opportunities but also present a number of challenges.

Precise localization of a rib lesion for its resection remains a challenge because of multiple factors including nonpalpable pathology, unfavorable body habitus, inaccurate clinical examination, and unreliable rib count on physical examination, unfavorable lesion location within a rib (its posterior aspect), and resection of sclerotic lesions with grossly intact rib cortex. We describe a novel rib localization technique that eliminates potential mistakes and avoids resection of an inappropriate rib. Our method of rib localization includes placement of metallic coils by interventional radiologists under computed tomography guidance where two coils are deployed within the intercostal spaces, one superior and one inferior to the rib lesion. Intraoperative use of fluoroscopy results in precise localization of rib lesions even in cases where the pathology is not grossly apparent. We implemented this approach in 2014 and have since performed it in five patients for both lytic and sclerotic lesions. Placement of markers superficial to the intercostal spaces resulted in their displacement in one case. Successfully, we removed the correct ribs in each patient without technical difficulties or complications. Our series demonstrates a novel strategy for a highly accurate and relatively easy way to identify the exact portion of the rib for surgical resection. Intercostal space positioning of the coil markers superior and inferior to the lesion prevents their dislodgement during patient transport and positioning on the operating room table, which improves rib identification accuracy and reliability. When combined with intraoperative fluoroscopy, it will greatly eliminate resection of incorrect ribs.

Most biomaterial-associated infections are caused by opportunistic pathogens and bacteria that are regularly found within the microflora of the implant site. In addition, a biomaterial implant or device remains at risk of infection by hematogenous spread of bacteria disseminated from infections elsewhere in the body or from infected peri-implant tissue in revision surgery. The resulting infections are frequently accompanied by patient morbidity and discomfort and can lead to surgical replacement of the implant after lengthy, unsuccessful attempts to mitigate infections with antibiotic treatments. Therefore, extensive study is aiming to find new infection-resistant antimicrobial biomaterials and coatings for implants and devices to effectively reduce the incidence of biomaterial-associated infections. An overview of the in vitro and in vivo antimicrobial efficacies of the numerous biomaterials currently available is beyond the scope of this review. Herein, we provide a comprehensive review of bioactive glasses as biomaterial delivery systems for antimicrobial agents., (© 2016 The Society for Applied Microbiology.)

The aim of this study was to carry out a representative survey on the implementation of and experience with repairs of single-tooth restorations among dentists in the Canton of Zurich, Switzerland. An anonymous questionnaire was sent to all 1,411 dentists registered in the Canton of Zurich; 38.9% of the delivered questionnaires were returned and 35.3% could be evaluated. The statistical analysis comprised Kendall’s rank correlation coefficient (tau), Wilcoxon signed-rank tests, and Kruskal-Wallis tests. The level of significance was set at p≤0.05. Repair restorations are frequently made (composite: 98.5%, ceramic: 88.9%, crowns: 86.5%, metal: 54.6%, amalgam: 51.5%). Main indications for repairs were the partial loss of an existing restoration or of the adjacent dental hard substance, while restoration failures due to secondary caries were repaired to a lesser extent. The decision to repair is largely dependent on the size of the defect (90%), the size of the original restoration (63%), and the material of the failed restoration (84%). Repair restorations are most frequently made with composite following adequate conditioning of the repair surface. A majority of the dentists rate the lifespan of repair restorations as reduced in comparison with newly made restorations. In summary, repairs of defective single-tooth restorations are frequently performed by dentists in the Canton of Zurich, Switzerland, and constitute a well-established treatment procedure.