Metal ions and nanometallic materials in antitumor immunity: Function, application, and perspective.

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.

Engineering liquid metal-based nanozyme for enhancing microwave dynamic therapy in breast cancer PDX model.

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 H2O2 in the tumor microenvironment to generate O2, 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.

Common and Trace Metals in Alzheimer's and Parkinson's Diseases.

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.

New anti-cancer explorations based on metal ions.

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.

Transition metals and metal complexes in autophagy and diseases.

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.

Multienzymes activity of metals and metal oxide nanomaterials: applications from biotechnology to medicine and environmental engineering.

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.

p-Cymene metallo-derivatives: An overview on anticancer activity.

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.

Liquid metal based theranostic nanoplatforms: Application in cancer therapy, imaging and biosensing.

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.

Challenges in Bone Tissue Regeneration: Stem Cell Therapy, Biofunctionality and Antimicrobial Properties of Novel Materials and Its Evolution.

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.

Metallosis after knee replacement: a review.

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.

Does cup position differ between trabecular metal and titanium cups? A radiographic propensity score matched study of 300 hips.

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.

Metal complexes in medicine and pharmacy - the past and the present II.

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.

Improvement in Hyperphosphatemia Using Phosphate Education and Planning Talks.

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.

Radiometals for imaging and theranostics, current production, and future perspectives.

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.

Development of Natural Product-Conjugated Metal Complexes as Cancer Therapies.

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.

Mycobacteria, metals, and the macrophage.

Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate metal cation trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here, we describe the recent fascinating discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with copper and zinc, two metals which are essential nutrients in small quantities but are toxic in excess. M. tuberculosis has developed multi-faceted resistance mechanisms to protect itself from metal toxicity including control of uptake, sequestration inside the cell, oxidation, and efflux. The host response to infections combines this metal poisoning strategy with nutritional immunity mechanisms that deprive M. tuberculosis from metals such as iron and manganese to prevent bacterial replication. Both immune mechanisms rely on the translocation of metal transporter proteins to the phagosomal membrane during the maturation process of the phagosome. This review summarizes these recent findings and discusses how metal-targeted approaches might complement existing TB chemotherapeutic regimens with novel anti-infective therapies.

A systematic review of the influence of the implant-abutment connection on the clinical outcomes of ceramic and metal implant abutments supporting fixed implant reconstructions.

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.

Toxicity of Metal Oxide Nanoparticles.

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.

Cost Analysis of All-Polyethylene Compared to Metal-Backed Implants in Total Knee Arthroplasty.

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.

Applications of Metals for Bone Regeneration.

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.