Healthy Tissue Cells Research Articles

Considerations for the Use of the DNA Damage Marker γ‐H2AX in Disease Modeling, Detection, Diagnosis, and Prognosis

ABSTRACTBackgroundDNA double‐strand breaks are known to be the most lethal kind of DNA damage as they cause genomic instability. Visualization and quantification of these breaks are possible via staining of the phosphorylated histone H2A variant H2AX at serine 139 with the anti‐phospho‐histone H2AX (γ‐H2AX) antibody.MethodsThe literature was searched with the following keywords: DNA damage, double‐strand break, PBMC, DNA repair, H2AX, γ‐H2AX.DiscussionThis review discusses various methods for the quantification of γ‐H2AX and the use of γ‐H2AX in cell culture, tissue biopsies, and peripheral blood mononuclear cells. The current research into basal DNA damage as quantified by γ‐H2AX is discussed in relation to cancer.ConclusionsThis review suggests that γ‐H2AX has the potential for use in the prediction of cancer risk when applied to healthy tissue and peripheral blood mononuclear cells.

Evidence of Programmed Death-Ligand 1 Expression in a Highly Inflammatory Prostate: A Literature Review and Our Experience.

Chronic inflammation (CI), a common finding in the human prostate, is associated with the most frequent socially important prostate diseases: prostatitis, benign prostatic hyperplasia, and prostate adenocarcinoma. Programmed cell death protein 1 (PD-1) and its ligand (PD-L1) expression are induced on the surface of immune and epithelial cells of healthy and tumor tissues in response to various cytokines. Here, we provide a comprehensive review of the PD-1/PD-L1 pathway in the non- and peri-tumoral inflammatory prostate, focusing on the structure and expression of PD-L1 and the diverse biological functions of PD-L1 signaling in health, high-grade CI (National Institutes of Health, category IV prostatitis or histologic prostatitis), and immune-related diseases, including autoimmunity, tumor microenvironmental immunity, and immune privilege. This review explores the possible pathophysiological interpretations of clearly visible, selective, and strong PD-L1 expression in the immuno-inflammatory-induced and related, histologically distinct sites of this expression: the ductal lymphoepitheliallesions and prostatic granulomas.

A simulation study on the effect of penetration of gold nanoparticles in the cytoplasm of healthy eye organs on dose enhancement of brachytherapy

Purpose Special properties and recent advances in the synthesis and biomolecular functionalization of gold nanoparticles (GNPs) have led to the evolution of their use in biomedical applications such as photon radiotherapy. Simulation-based studies on the effect of various parameters that govern the dose enhancement due to utilizing GNPs have facilitated the progress of knowledge in this field. Due to their flexibility and easier accessibility compared with experimental works, simulations have the potential to be considered for pre-clinical tests and, therefore, should be close to the realistic conditions as much as possible. Materials and methods To this aim, the present work investigates the effect of the presence of GNPs that are accumulated in the cytoplasm of the constituent cells in healthy tissues of a human eye phantom, inspired by the published experimental results which report that non-target tissues also receive the drugs containing GNPs. The GNPs’ concentrations are assumed to decrease by moving from the tumor toward the depth of the phantom through a suggested pattern. The MCNPX Monte Carlo code is used for the simulations. Results The results show that for four concentrations tested, the dose enhancement factor in the shallower layer reaches 6, and decreases to 1.2 in the last layer. The dose enhancements are also examined for critical structures of the iris, cornea, sclera, and lens, showing maximum deviations of about 3 to 200% compared with the absence of GNPs in the healthy tissue. Considering the reported doses to the lens by clinical institutions, the effect of penetration of GNPs to deep layers on treatment time is also investigated. Conclusions The results show that the penetration of GNPs from the tumor toward healthy tissues strongly controls the dose enhancement over the various eye structures and emphasizes the importance of modeling the GNPs’ distribution in the medium on the overall dose enhancement. Considering the current challenges in the clinical use of GNPs, more effort needs to be made to reach an effective endpoint in treatment.

The safety and efficacy of adipose tissue-derived exosomes in treating mild to moderate plaque psoriasis: A clinical study

AimThis study evaluates the safety and efficacy of autologous adipose-derived mesenchymal stem cell-derived exosomes as a treatment for Psoriasis, a chronic immune-related skin and joint disorder, compared to current treatments like topicals, phototherapy, and systemic. Materials and methodsThe study isolated exosomes from Mesenchymal Stem Cells(MSCs) of healthy adipose tissue using ultracentrifugation. 12 patients with plaque psoriasis were divided into three groups and given single doses of exosomes. Tissue samples were collected pre- and post-treatment and examined for inflammatory(TNFα, IL23, IL17, IFNγ, CD3) and anti-inflammatory (FOXP3, IL10) markers. The severity of the lesion was also evaluated. Key findingsIn this study, it was found that erythema and induration (P < 0.05) decreased significantly in patients receiving 200 μg. Still, this reduction in scaling was not significant, the thickness was significantly reduced in patients receiving 100 and 200 μg doses (P < 0.05). H&E evaluation showed that the decreasing trend in these patients was not significant (P > 0.05). IHC evaluation in patients receiving doses of 100 and 200 μg showed a decrease in the presence of IL17 (P < 0.05, <0.001) & CD3(P < 0.001, <0.05) and a considerable increase in FOXP3(P ≤ 0.001), in the tissue samples of the patients. Examining the expression of inflammatory factors also shows that dose 200 μg decreased the expression of IL17(P > 0.05), IFNγ(P > 0.05), IL23(P < 0.05), & TNFα(P ≤ 0.05) and increased the expression of the anti-inflammatory factor IL10(P < 0.05). SignificanceThe study indicates that a 200 μg dose is optimal for patients, but a larger patient population is needed for more reliable results. Additionally, higher doses or multiple injections with specific intervals can increase confidence.

Positronium lifetime measurement using a clinical PET system for tumor hypoxia identification

Positronium (Ps) imaging has been recently spotlighted for its potential applications in nuclear medicine. Among them, we expect that the Ps lifetime can be a sensor for tumor hypoxia; hence, we are aiming to achieve Ps lifetime imaging, Quantum PET (Q-PET), based on whole gamma imaging (WGI). A linear correlation was previously shown between the Ps lifetime and the oxygen partial pressure (pO2) in water by using a bench-top detector system. However, nobody has ever measured the Ps lifetimes for pO2 values of 10 mmHg and 40 mmHg, corresponding to hypoxic cancer cells and healthy tissue cells, respectively. Therefore, this study aimed at measuring the Ps lifetime of 22Na solutions each having such tiny differences in the pO2 value. For possible extension toward imaging, we used VRAIN, a clinical brain-dedicated time-of-flight (TOF) PET system. The pO2 values of the 22Na solutions were adjusted to 0, 10, 40, and 160 (air) mmHg by adjusting the inflow of nitrogen gas. Each 22Na solution was placed near the center of the detector geometry and measured. Three different energy windows (EWs) for 1275 keV gamma detection were compared (1100–1500 keV, 900–1500 keV and 700–1500 keV). Due to the increased number of events, the error values (σ: standard deviation) of the calculated Ps lifetimes decreased as the EW widened. The optimized EW was determined to be 700–1500 keV, which showed the lowest error value. The Ps lifetime values gradually became shorter as the pO2 values increased. The Ps lifetime values at 0 mmHg and 160 mmHg were 1.9389 ± 0.0025 ns and 1.9104 ± 0.0024 ns at the EW of 700–1500 keV. The difference between the lifetime values was more than three times the errors (±3σ), and we considered it was a statistically significant difference. The Ps lifetime values of 10 mmHg and 40 mmHg were 1.9360 ± 0.0026 ns and 1.9291 ± 0.0024 ns at the same condition, and the difference could be distinguished with an error value of more than ± 1σ.

Ce3D-IBEX: Achieving Multiplex 3-dimensional Imaging for Deep Phenotyping of Cells in Tissues

Abstract 2D multiplexed antibody-based imaging provides a framework to study cell-cell interactions in thin tissue sections but lacks the ability to interrogate spatial relationships in larger 3D micro-anatomical structures. Several methods for 3D imaging of optically cleared tissue exist, but current approaches do not provide a deep phenotyping capability as afforded by high content 2D imaging. Here,we developed a method to overcome this constraint by combining a fast hydrophilic tissue clearing technique, clearing-enhanced 3D (Ce3D), and the recently developed Iterative Bleaching Extends Multiplexity (IBEX) technique together with a robust image registration algorithm suite to create a highly multiplex 3D imaging method: Ce3D-IBEX. It has been used to analyze murine lung, lymph nodes, small intestine, retina, tumor, and cornea as well as human retina, kidney, liver, tonsil, and jejunum, yielding seamless views of large-scale tissue structures while enabling visualization of high dimensional phenotypic markers at single-cell resolution, permitting the identification of discrete cell subsets, quantification of protein expression level and their mutual spatial association within tissue structures. To date, 25+ markers have been visualized in a single 3D sample. This represents a major advance in the emerging field of highly multiplexed 3D imaging. With aims to open new avenues for characterization of spatial dynamics of immune cells in healthy and diseased tissue.

Azobenzene‐Based Linker Strategy for Selective Activation of Antibody–Drug Conjugates

AbstractExisting antibody–drug conjugate (ADC) linkers, whether cleavable or non‐cleavable, are designed to release highly toxic payloads or payload derivatives upon internalisation of the ADCs into cells. However, clinical studies have shown that only &lt;1 % of the dosed ADCs accumulate in tumour cells. The remaining &gt;99 % of ADCs are nonspecifically distributed in healthy tissue cells, thus inevitably leading to off‐target toxicity. Herein, we describe an intelligent tumour‐specific linker strategy to address these limitations. A tumour‐specific linker is constructed by introducing a hypoxia‐activated azobenzene group as a toxicity controller. We show that this azobenzene‐based linker is non‐cleavable in healthy tissues (O2 &gt;10 %), and the corresponding payload derivative, cysteine‐appended azobenzene‐linker–monomethyl auristatin E (MMAE), can serve as a safe prodrug to mask the toxicity of MMAE (switched off). Upon exposure to the hypoxic tumour microenvironment (O2&lt;1 %), this linker is cleaved to release MMAE and fully restores the high cytotoxicity of the ADC (switched on). Notably, the azobenzene linker‐containing ADC exhibits satisfactory antitumour efficacy in vivo and a larger therapeutic window compared with ADCs containing traditional cleavable or non‐cleavable linkers. Thus, our azobenzene‐based linker sheds new light on the development of next‐generation ADC linkers.

Azobenzene-Based Linker Strategy for Selective Activation of Antibody-Drug Conjugates.

Existing antibody-drug conjugate (ADC) linkers, whether cleavable or non-cleavable, are designed to release highly toxic payloads or payload derivatives upon internalisation of the ADCs into cells. However, clinical studies have shown that only <1 % of the dosed ADCs accumulate in tumour cells. The remaining >99 % of ADCs are nonspecifically distributed in healthy tissue cells, thus inevitably leading to off-target toxicity. Herein, we describe an intelligent tumour-specific linker strategy to address these limitations. A tumour-specific linker is constructed by introducing a hypoxia-activated azobenzene group as a toxicity controller. We show that this azobenzene-based linker is non-cleavable in healthy tissues (O2 >10 %), and the corresponding payload derivative, cysteine-appended azobenzene-linker-monomethyl auristatin E (MMAE), can serve as a safe prodrug to mask the toxicity of MMAE (switched off). Upon exposure to the hypoxic tumour microenvironment (O2<1 %), this linker is cleaved to release MMAE and fully restores the high cytotoxicity of the ADC (switched on). Notably, the azobenzene linker-containing ADC exhibits satisfactory antitumour efficacy in vivo and a larger therapeutic window compared with ADCs containing traditional cleavable or non-cleavable linkers. Thus, our azobenzene-based linker sheds new light on the development of next-generation ADC linkers.

Tumor-specific activation of folate receptor beta enables reprogramming of immune cells in the tumor microenvironment.

Folate receptors can perform folate transport, cell adhesion, and/or transcription factor functions. The beta isoform of the folate receptor (FRβ) has attracted considerable attention as a biomarker for immunosuppressive macrophages and myeloid-derived suppressor cells, however, its role in immunosuppression remains uncharacterized. We demonstrate here that FRβ cannot bind folate on healthy tissue macrophages, but does bind folate after macrophage incubation in anti-inflammatory cytokines or cancer cell-conditioned media. We further show that FRβ becomes functionally active following macrophage infiltration into solid tumors, and we exploit this tumor-induced activation to target a toll-like receptor 7 agonist specifically to immunosuppressive myeloid cells in solid tumors without altering myeloid cells in healthy tissues. We then use single-cell RNA-seq to characterize the changes in gene expression induced by the targeted repolarization of tumor-associated macrophages and finally show that their repolarization not only changes their own phenotype, but also induces a proinflammatory shift in all other immune cells of the same tumor mass, leading to potent suppression of tumor growth. Because this selective reprogramming of tumor myeloid cells is accompanied by no systemic toxicity, we propose that it should constitute a safe method to reprogram the tumor microenvironment.

The impact of radio-chemotherapy on tumour cells interaction with optimal control and sensitivity analysis

Oncologists and applied mathematicians are interested in understanding the dynamics of cancer-immune interactions, mainly due to the unpredictable nature of tumour cell proliferation. In this regard, mathematical modelling offers a promising approach to comprehend this potentially harmful aspect of cancer biology. This paper presents a novel dynamical model that incorporates the interactions between tumour cells, healthy tissue cells, and immune-stimulated cells when subjected to simultaneous chemotherapy and radiotherapy for treatment. We analysed the equilibria and investigated their local stability behaviour. We also study transcritical, saddle–node, and Hopf bifurcations analytically and numerically. We derive the stability and direction conditions for periodic solutions. We identify conditions that lead to chaotic dynamics and rigorously demonstrate the existence of chaos. Furthermore, we formulated an optimal control problem that describes the dynamics of tumour-immune interactions, considering treatments such as radiotherapy and chemotherapy as control parameters. Our goal is to utilize optimal control theory to reduce the cost of radiotherapy and chemotherapy, minimize the harmful effects of medications on the body, and mitigate the burden of cancer cells by maintaining a sufficient population of healthy cells. Cost-effectiveness analysis is employed to identify the most economical strategy for reducing the disease burden. Additionally, we conduct a Latin hypercube sampling-based uncertainty analysis to observe the impact of parameter uncertainties on tumour growth, followed by a sensitivity analysis. Numerical simulations are presented to elucidate how dynamic behaviour of model is influenced by changes in system parameters. The numerical results validate the analytical findings and illustrate that a multi-therapeutic treatment plan can effectively reduce tumour burden within a given time frame of therapeutic intervention.

In silico, in vitro, and in vivo validation of a microwave imaging system using a low‐profile Ultra Wide Band Archimedean spiral antenna to detect skin cancer

AbstractMicrowave imaging (MI) is a noninvasive and nonionizing procedure for detection of cancerous cells in healthy body tissues using radiofrequency (RF) and microwaves. The procedure involves the use of Ultra Wide Band (UWB) antennas for sensing purposes. Therefore, this research article presents the design, development, and testing of a low‐profile UWB Archimedean spiral microstrip‐patch antenna (ASMA) for detection of skin cancer using monostatic radar‐based microwave imaging. The proposed ASMA consists of a spiral resonator with a defective ground structure and a slotted microstrip feed line with dimensions of 38 × 38 × 0.87 mm3. The proposed antenna shows an impedance bandwidth for the frequency range of 2.2–13.9 GHz, with a peak gain of 6.8 dB at 7.8 GHz. In silico analysis of the proposed ASMA for MI is carried out with Gaustav model using Computer Simulation Technology Microwave Studio. To validate the performance of the ASMA as a sensor for MI, a prototype of the same is fabricated and a four‐layered bio‐phantom of the human forearm is prepared for in vitro and in vivo testing of the proposed procedure. The validation of ASMA radiation properties is done using a Vector Network Analyser (E‐5063A) (VNA) and an anechoic chamber with the fabricated antenna at 10 mm away from the prepared bio‐phantom. The recorded S parameter data with bio‐phantom and the VNA is processed using different beamforming algorithms like Delay and Sum and Coherent Factor‐Delay Multiply and Sum (CF‐DMAS) to reconstruct the image of the scanned area. The reconstructed images are 97%–98% accurate. The proposed ASMA sensor is also safe for human exposure as it has a specific absorption rate of 0.0546 W/Kg at 5 GHz that complies with the safety guidelines of the Federal Communications Commission to minimize potential health risks associated with exposure to RF and microwave radiation.

THE ROLE OF REPAIR PROCESSES IN THE FORMATION OF RADIOSENSITIVITY OF HEALTHY AND TUMOUR CELLS IN HUMANS

Despite significant progress in the development and implementation of new radiotherapeutic techniques over the past decade and positive results of radiotherapy for cancer patients, overall and progression-free survival rates are still poor. The analysis of literature data and our own research in the field of clinical radiobiology and radiation oncology shows that cellular DNA repair systems increase the radioresistance of tumours and thus hinder the improvement of the effectiveness of patient therapy. The role of repair processes in shaping the radiosensitivity of tumours compared to healthy tissues is discussed in detail, and their differences are described. It is emphasized that the repair of irradiated DNA damage in tumour cells is more intensive than in healthy tissue cells due to increased expression of repair enzymes. Together with the instability of the tumour cell genome, this causes a large variation in their radiosensitivity and indicates the priority of research aimed at finding and developing radioprotectors to protect the genome of healthy cells from the environment of the irradiated tumour without affecting (reducing) its radiosensitivity. Such a way to optimize the results of therapeutic radiation will help minimize radiation complications that require additional therapy and worsen the quality of life of treated patients.

Immunotherapy Using CAR T Cells: Current Challenges and Solutions to Overcome On-Target, Off-Tumor Toxicity

Blood cancers like leukemia and lymphoma currently affect approximately 1.3 million Americans and account for about 10% of all cancer related deaths in the US. However, immunotherapies such as chimeric antigen receptor (CAR) T cells have been developed to provide a cure for many of these patients where refractory/relapsed disease was previously a death sentence. Current approaches for CAR T treatment involve the modification of autologous T cells ex vivo in order to engineer these cells with a CAR which binds to a B cell cancer antigen and results in T cell mediated clearance of the target tumor cell. With exception to CD19 and other B cell antigens, targeting other tumor cell types has been largely unsuccessful for many reasons, including antigen escape and on-target off-tumor toxicity (OTOT), which occurs when the target cancer antigen is co-expressed on healthy tissue cells and becomes targeted by the CAR T cell therapy. The purpose of this review is to understand the challenges in antigen escape and OTOT. We will discuss current strategies to overcome these obstacles which allow CAR T therapy to be more applicable to other tumor cell types. We will highlight novel approaches such as logic gated CARs and epitope editing as potential solutions to overcome antigen escape and OTOT.

Selective reprogramming of regulatory T cells in solid tumors can strongly enhance or inhibit tumor growth.

Folate receptor delta (FRδ) has been used as a biomarker for regulatory T cells (Tregs), because its expression is limited to Tregs and ovum. Although FRδ is unable to bind folate, we have used molecular docking software to identify a folate congener that binds FRδ with high affinity and have exploited this FRδ-specific ligand to target attached drugs (imaging agents, immune activators, and immune suppressors) specifically to Tregs in murine tumor xenografts. Analysis of treated tumors demonstrates that targeting of a Toll-like receptor 7 agonist inhibits Treg expression of FOXP3, PD-1, CTLA4, and HELIOS, resulting in 40-80% reduction in tumor growth and repolarization of other tumor-infiltrating immune cells to more inflammatory phenotypes. Targeting of the immunosuppressive drug dexamethasone, in contrast, promotes enhanced tumor growth and shifts the tumor-infiltrating immune cells to more anti-inflammatory phenotypes. Since Tregs comprise <1% of cells in the tumor masses examined, and since the targeted drugs are not internalized by cancer cells, these data demonstrate that Tregs exert a disproportionately large effect on tumor growth. Because the targeted drug did not bind to Tregs or other immune cells in healthy tissues, the data demonstrate that the immunosuppressive properties of Tregs in tumors can be manipulated without causing systemic toxicities associated with global reprogramming of the immune system.

Optimizing a Novel Fate-Mapping Strategy to Assess Tissue Resident Macrophages in Muscle Regeneration

Tissue resident macrophages (TRMs) are heterogenous innate immune cells involved in tissue homeostasis and repair, yet their role in muscle regeneration is currently unknown. TRMs differ from classical monocyte-derived macrophages (MDMs) in both ontogeny and function. Our inability to differentiate TRMs from MDMs has limited the development of subset specific immunotherapies. The novel Cx3cr1CreER/+:RosaTd/+ fate-mapping mouse model employs tamoxifen inducible labeling of MDMs and TRMs with a TdTomato reporter (Td) that persists only in self-renewing TRMs, while MDMs are replaced by Td- monocyte progenitors over a 4-week period. This strategy has been successfully used in adult mice heart and brain tissue. However, in the skeletal muscle, expression level of the Cx3cr1 reporter gene is unknown. We assessed muscle TRM Cx3cr1 expression in neonate (P3), young (P21), and adult (10wk) mice to optimize a pulse/chase strategy to label muscle TRMs with the Td reporter. Like heart and brain tissue, we found muscle TRMs express high levels of Cx3cr1 throughout development and adulthood suggesting viability of this strategy. We performed a single injection of tamoxifen in adult Cx3cr1CreER/+:RosaTd/+ mice and showed ~20% induction in blood monocytes and muscle TRMs. Although Td induction was poor, levels were similar between the blood and muscle, suggesting accuracy of the model. The next step is to optimize tamoxifen administration to achieve &gt;90% labelling in blood and muscle. To assess spatial localization of TRMs with muscle resident stem cells (satellite cells) we optimized immunofluorescence staining on tissue sections. We found a statistically significant increase in colocalization of macrophages with satellite cells in healthy and injured gastrocnemius tissue, consistent with their predicted role in satellite cell proliferation. Once complete, our fate-mapping approach will allow for the labelling of muscle TRM subsets and reveal their role in the regeneration process.

Stability and bifurcation analysis for a fractional-order cancer model with two delays

Considering that healthy tissue cells and tumor cells restrain each other’s the average growth rate with a corresponding delay, a fractional-order cancer model with time delays is established. Firstly, by selecting different delays as bifurcation parameters, the delay-independent stability and Hopf bifurcation conditions of such system are derived. Then, some interesting dynamical phenomena of the system under different initial values can be observed, such as a pair of coexisted stable periodic solution, equilibrium point transition, and even chaos. Finally, some numerical simulations are exhibited to substantiate the obtained results. The work reveals that the fractional order and delays play an important role in the stability behavior and bifurcation characteristics of the system, and that a suitable control strategy of the system can be designed by selecting reasonable system parameters (fractional orders and time delays).

The Effect of Xevinapant Combined with Ionizing Radiation on HNSCC and Normal Tissue Cells and the Impact of Xevinapant on Its Targeted Proteins cIAP1 and XIAP

The poor prognosis of HNSCC is partly due to treatment resistance. The SMAC mimetic Xevinapant is a promising new approach to targeted cancer therapy. Xevinapant inhibits cIAP1/2 and XIAP, leading to apoptosis, necroptosis and inhibition of prosurvival signaling. Combining Xevinapant with IR could improve therapeutic potential. The effect of Xevinapant in combination with IR on HNSCC and healthy tissue cells was investigated. Cell growth, cell death, clonogenic survival and DNA double-strand breaks (DSBs) were studied, and intracellular cIAP1 and XIAP levels were evaluated. Xevinapant had cytostatic and cytotoxic, as well as radiosensitizing, effects on the malignant cells, while healthy tissue cells were less affected. Apoptotic and necrotic cell death was particularly affected, but the increase in residual DSBs and the reduced survival implied an additional effect of Xevinapant on DNA damage repair and other cell inactivation mechanisms. cIAP1 and XIAP levels varied for each cell line and were affected by Xevinapant and IR treatment. There was an association between higher IAP levels and increased cell death. Xevinapant appears to be a potent new drug for HNSCC therapy, especially in combination with IR. IAP levels could be an indicator for impaired DNA damage repair and increased susceptibility to cellular stress.

A Principal Componet Analysis to detect cancer cell line aggressiveness

In this paper, we propose the use of Principal Component Analysis (PCA) as a new post-processing method for the detection of breast and bone cancer cell lines cultured in vitro using a microwave biosensor. MDA-MB-231 and MCF7 breast cancer cell lines and SaOS-2 and 143B osteosarcoma cell lines were characterized using a circular patch resonator in the 1 MHz – 3 GHz frequency range. The return loss of each cancer cell line was analyzed, and the differences among each other were determined through Principal Component Analysis according to a protocol previously proposed mainly for electrocardiogram processing and X-ray photoelectron spectroscopy. Our results showed that the four cancer cell lines analyzed exhibited peculiar dielectric properties when compared to each other and the growth medium, confirming that PCA could be employed as an alternative methodology to analyze microwave characterization of cancer cell lines which, in turn, may be deeply exploited as a tool for the detection of cancer cells in healthy tissues.

Evaluation of IL-4, MIP-1α, and MMP-9 gene expression levels in peri-implant tissues in peri-implantitis.

This case-control study evaluated the gene expression levels of interleukin (IL)-4, macrophage inflammatory protein type 1 alpha (MIP-1α), and metalloproteinase (MMP)-9, factors involved in the formation of giant cells in healthy peri-implant tissue and peri-implantitis. Thirty-five subjects (15 healthy and 20 with peri-implantitis), who met the inclusion and exclusion criteria, were included in this study. The peri-implant tissue biopsies were subjected to total RNA extraction, DNAse treatment, and cDNA synthesis. Subsequently, the reaction of real-time PCR was performed to evaluate the gene expression levels of IL-4, MIP-1α, and MMP-9 concerning the reference gene. IL-4 gene expression showed higher (18-fold) values in the Peri-Implantitis Group of Patients when compared with the Healthy (Control) Group (p<0.0001). Although MIP- 1α and MMP-9 gene expression levels were higher in diseased implants, they showed no significant differences (p=0.06 and p=0.2337), respectively. Within the limitations of this study, the results showed that in tissues affected by peri-implantitis, only levels of Il-4 were increased when compared with tissues in the control group.

Catalytic Nanomedicine as a Therapeutic Approach to Brain Tumors: Main Hypotheses for Mechanisms of Action.

Glioblastoma multiforme (GBM) is the most aggressive primary malignant tumor of the brain. Although there are currently a wide variety of therapeutic approaches focused on tumor elimination, such as radiotherapy, chemotherapy, and tumor field therapy, among others, the main approach involves surgery to remove the GBM. However, since tumor growth occurs in normal brain tissue, complete removal is impossible, and patients end up requiring additional treatments after surgery. In this line, Catalytic Nanomedicine has achieved important advances in developing bionanocatalysts, brain-tissue-biocompatible catalytic nanostructures capable of destabilizing the genetic material of malignant cells, causing their apoptosis. Previous work has demonstrated the efficacy of bionanocatalysts and their selectivity for cancer cells without affecting surrounding healthy tissue cells. The present review provides a detailed description of these nanoparticles and their potential mechanisms of action as antineoplastic agents, covering the most recent research and hypotheses from their incorporation into the tumor bed, internalization via endocytosis, specific chemotaxis by mitochondrial and nuclear genetic material, and activation of programmed cell death. In addition, a case report of a patient with GBM treated with the bionanocatalysts following tumor removal surgery is described. Finally, the gaps in knowledge that must be bridged before the clinical translation of these compounds with such a promising future are detailed.