In this work, we present and experimentally validate a fully implantable radio frequency system capable of inducing mild heating as a response to a received electromagnetic wave. The heating process is initiated by a transmitter antenna located outside the human body. It is received by a compact meandered miniaturized loop antenna integrated through a differential matching network with a planar inductive resonant LC heating circuit. The design process incorporates the complexities of the human body propagation channel, and the system is validated through phantom-based experiments and ex-vivo testing. Experimental results demonstrate strong agreement with simulation data, and thermal assessments reveal a consistent and controlled temperature increase, confirming the effectiveness of the proposed system. The experimental results provide a 0.01 degrees C increase in temperature per minute in phantom testing, whereas ex-vivo testing reveals an average change in temperature of around 0.06 degrees C per minute when relying on stacked organs from sacrificed mice. Such subtle temperature increases are in the range reported to modulate metabolic activity in biological tissues. This work establishes a foundational platform for future medical interventions utilizing continuous, non-invasive wireless heating within the human body.

This paper presents a microwave sensing platform for quantitative evaluation of creatinine concentration in urine using a 3D-printed bifilar helical resonant structure. The proposed sensing system integrates two conductive helices with a slotted cylindrical shell incorporating volumetric split-ring resonators, enabling enhanced confinement of near-field electromagnetic energy within the sensing region. This design strengthens the interaction between the electromagnetic fields and the urine sample, resulting in increased sensitivity to variations in creatinine concentration. The sensing structure is fabricated using precision additive manufacturing to ensure high reproducibility and stable electromagnetic performance. Operating in the 4–6.5 GHz frequency range, the sensor response is characterized through measured scattering parameters, which are processed using artificial intelligence techniques for both regression and classification tasks. Gaussian Process regression is employed to estimate creatinine concentration, achieving a mean absolute relative difference (MARD) of 10% for artificial urine samples, between 6.94% and 10% for ex-vivo rat studies, and 7.2% for clinical human urine samples. In addition, a support vector machine classifier is used to detect creatinine in the presence of common interferers, achieving an accuracy ranging from 92.5% to 97.5%, a sensitivity between 90% and 100%, and a specificity between 91.6% and 100%. The proposed platform demonstrates a robust, reagent-free, and noninvasive approach for real-time creatinine monitoring, offering promising potential for future point-of-care diagnostic applications and early assessment of kidney function.

Diabetic kidney disease (DKD) is a major complication of diabetes characterized by progressive renal dysfunction driven by oxidative stress and inflammation involving mammalian target of rapamycin (mTOR) and NADPH oxidase (NOX) pathways. Mesenchymal stem cells (MSCs) have gained attention for their regenerative and immunomodulatory properties in attenuating DKD, but the mechanisms behind their protective effects are still being explored. Moreover, concerns regarding tumorigenic risks hinder their direct clinical use. In this study, we compared MSCs and their conditioned media (MSCs-CM; secretome) in a type 1 diabetic rodent model, demonstrating that both treatments attenuated glomerular injury, preserved podocyte integrity, reduced NOX4 expression and activity, and tempered inflammation, by inhibiting mTORC1 and mTORC2 signaling. Importantly, MSCs-CM replicated the renoprotective effects of MSCs, indicating that soluble factors mediate these benefits. To our knowledge, this is the first study to directly compare MSCs and their conditioned media (MSCs-CM) in DKD, revealing that MSCs-CM delivers equivalent therapeutic efficacy while circumventing the safety concerns inherent to cell-based therapies. These findings identify the mTOR/NOX axis as a therapeutic target and support MSCs-CM as a promising, safer, cell-free alternative for DKD treatment, potentially advancing regenerative strategies to mitigate diabetic renal injury. ARTICLE HIGHLIGHTS:Despite advances in diabetes management, diabetic kidney disease (DKD) remains a leading cause of end-stage renal disease. We investigated whether mesenchymal stem cells (MSCs) and their conditioned medium, containing the MSC-derived secretome, protect against DKD by modulating the mammalian target of rapamycin (mTOR)/NADPH oxidase (NOX) pathway. MSCs and MSCs-conditioned medium both reduced kidney injury, podocyte structural integrity, oxidative stress, and inflammation by inhibiting mTORC1/mTORC2 and NOX4. MSCs-conditioned medium offers a safe, secretome-based, cell-free approach for DKD therapy.

Colorectal cancer (CRC) remains a leading cause of cancer morbidity worldwide, highlighting the need for improved therapies. Metformin, a widely used antihyperglycemic agent, has gained attention for its potential antitumor properties. In this study, we evaluated the effects of the tumor suppressor genes TP53 and CDKN1A on metformin responsiveness in a KRAS-mutant CRC in vitro model using HCT116 cells harboring a G13D mutation in KRAS. Using parental (p53+/+, p21+/+) and isogenic knockout cell lines, we assessed cell-cycle distribution and transcriptomic responses following metformin treatment. In parental wild-type cells, metformin exposure was associated with a dose- and time-dependent reduction in cell viability and an increased proportion of cells in the G0/G1 phase, with significance levels across treatment conditions ranging from p = 0.03 to p < 0.0001. Loss of p53 or p21 was associated with attenuated cellular responses to metformin, with p21-deficient cells responding primarily at higher doses and prolonged exposure (72 h). Transcriptomic profiling revealed extensive differential gene expression in parental cells (1399 DEGs), compared with more limited responses in p53-/- (270 DEGs) and p21-/- cells (32 DEGs). Differentially expressed genes associated with MAPK signaling (DUSP5) and inflammatory regulation (TNFAIP3) were observed across genotypes, whereas pathway enrichment of DNA replication and chromatin organization was specific to p53-deficient cells. These findings provide a transcriptomic and phenotypic characterization of genotype-dependent cellular responses to metformin and establish a basis for future mechanistic and functional validation studies.

Diabetic kidney disease (DKD) and diabetic cardiomyopathy continue to drive excess morbidity and mortality in diabetes, underscoring a critical gap between mechanistic insight and clinical translation. Growth differentiation factor-15 (GDF-15), a stress-inducible cytokine of the transforming growth factor-β superfamily, has emerged as a critical biomarker and putative modulator of metabolic inflammation. Yet the field remains divided on a fundamental question: is GDF-15 simply reporting tissue distress, or does it shape disease trajectories? In this article, we explore how GDF-15 may both signal and shape DKD and cardiovascular disease. Drawing on evidence from experimental models, longitudinal clinical studies, and multi-omics analyses, we highlight the context-dependent biology of GDF-15, protective during acute metabolic or inflammatory stress but potentially pathogenic when chronically elevated in diabetes. We examine its regulation via the GFRAL-RET signaling axis, its segment-specific expression across renal tubular compartments, and its emerging role in cardiac remodeling and metabolic inflammation. Recent clinical data position circulating GDF-15 as an early and sensitive indicator of DKD progression and cardiovascular events. At the same time, mechanistic studies increasingly implicate sustained GDF-15 signaling in mitochondrial dysfunction, inflammatory amplification, and maladaptive tissue remodeling. Together, these observations place GDF-15 at a critical inflection point between risk stratification and disease mechanism. A key unresolved challenge is defining when, where, and how GDF-15 signaling exerts adaptive versus maladaptive effects-knowledge that will be essential for determining whether GDF-15 should be targeted, harnessed, or restrained in diabetes. ARTICLE HIGHLIGHTS:GDF-15 is a stress-responsive cytokine of the TGF-β superfamily regulated by p53, mitochondrial dysfunction, and inflammatory signaling. Circulating GDF-15 levels are low under physiological conditions but rise markedly in response to cellular and metabolic stress. Elevated GDF-15 predicts incident diabetes and reflects hyperglycemia-induced oxidative and cellular stress. GDF-15 correlates with albuminuria, estimated glomerular filtration rate decline, and progression risk in diabetic kidney disease. Increased levels predict heart failure, myocardial infarction, and cardiovascular mortality in diabetes. Targeting the GDF-15-GFRAL axis and leveraging GDF-15 as a biomarker offer emerging translational potential.

Myocardial ischaemia continues to be a predominant global cause of mortality, leaving survivors with compromised quality of life and significant loss of functional cardiomyocytes. The main therapeutic approach, which attempts to restore heart function, generally involves myocardial reperfusion. However, this intervention is frequently complicated by the occurrence of myocardial reperfusion injury, which undermines its therapeutic benefits. Consequently, there is an increasing focus on alternative regenerative approaches, such as stem and progenitor cell therapies. Since their initial and successful use in oncology, stem cells have emerged as promising tools for mitigating various pathological conditions. Nonetheless, their efficacy in post-ischaemic myocardial environments is questioned due to their rapid degradation following delivery. Interestingly, small extracellular vesicles, particularly exosomes secreted by stem cells, demonstrate reparative properties akin to those of the stem cells themselves. Indeed, evidence strongly shows that exosomes derived from mesenchymal stem cells, cardiac progenitor cells, and induced pluripotent stem cells exert anti-apoptotic and pro-angiogenic effects in post-ischaemic cardiomyocytes while concomitantly offering protection against myocardial reperfusion injury. In this review, we critically appraise the pivotal findings supporting the potential clinical application of stem cell-derived exosomes, and underscore key considerations necessary to optimise their therapeutic efficacy.

Background: Diabetic kidney disease (DKD) represents a chronic microvascular complication with diabetes, affecting around one-third of diabetic individuals. Despite current therapies, progression to end-stage kidney disease remains a challenge. Abnormal hyperphosphorylation of the Tau protein is implicated in various age-related diseases. This study aimed to explore the link between renal Tau protein hyperphosphorylation and kidney damage in type 2 diabetes mellitus (T2DM). Methods: Sprague Dawley rats were administered lithium chloride (LiCl), an inhibitor of a glycogen synthase kinase-3 (GSK3) inhibitor known to reduce Tau hyperphosphorylation. LiCl was administered either daily or every other day at a dosage of 1 mmol/kg. The effects of LiCl on kidney function were assessed through proteinuria, the kidney-to-bodyweight ratio, inflammation, fibrosis, and TGF-β1 expression levels. Results: Diabetic rats exhibited increased proteinuria, renal hypertrophy, inflammation, fibrosis, and elevated TGF-β1 expression. Lithium chloride treatment reduced kidney hypertrophy, inflammation, and fibrosis, indicating that Tau hyperphosphorylation contributes to the pathogenesis of DKD. LiCl also regulated TGF-β1 expression, which was associated with improved renal outcomes. Conclusions: The inhibition of Tau hyperphosphorylation by lithium chloride offers a potential therapeutic strategy for mitigating kidney damage in diabetic kidney disease. This study proposes LiCl as a novel treatment approach to attenuate DKD progression.

Diabetes Mellitus is the leading risk factor for kidney failure, yet current biomarkers such as urinary albumin-to-creatinine ratio (UACR) lack tissue specificity and sensitivity for early detection of Diabetic Kidney Disease (DKD). DNA methylation provides insight into kidney-specific epigenetic mechanisms, but most studies rely on blood rather than renal tissue. We evaluated the feasibility of profiling DNA methylation from archived formalin-fixed paraffin-embedded (FFPE) kidney biopsies to uncover renal epigenetic signatures of DKD. Genomic DNA was extracted from FFPE biopsies of nine individuals with type 2 diabetes and varying albuminuria. DNA methylation was enriched using the MethylMiner protocol and quantified by methyl-CpG-binding domain qPCR (MBD-qPCR), targeting seven DKD-associated Differentially Methylated Gene Network (DDN): MTOR, RPTOR, IRS2, COL1A2, TXNRD1, LCAT, and SMPD3. Despite DNA degradation in archival FFPE samples, methylation profiling was successful. A strong inverse correlation was observed between DDN methylation and UACR (Pearson R = –0.79, p = 0.01). Hypomethylation of MTOR, COL1A2, and LCAT was particularly evident in individuals with elevated UACR, highlighting their potential as markers of DKD severity. This pilot study demonstrates the feasibility of MBD-qPCR-based DNA methylation profiling from FFPE kidney biopsies, supporting the use of archival tissue epigenetic biomarker discovery and risk stratification in DKD.

This article discusses the design of circularly polarized V-band antenna arrays for continuous and wireless blood glucose monitoring. The proposed system is designed to be integrated into earrings to sense glucose variations at a distance and without physical contact with the sensed area. Sensing occurs when one antenna array transmits its radiated beam across the neck veins to be received by a second antenna array integrated into a second earring on the other side of the neck. The analysis of received signals versus transmitted signals using machine learning algorithms enables this system to track glucose variation in blood instantaneously with great fidelity. Experiments executed on fetal bovine serum (FBS) solutions and in vivo experiments on animal models demonstrate high accuracy in the ability of the proposed antenna array system to continuously track glucose concentrations across the diabetic range [30-500 mg/dl]. Furthermore, executed clinical studies reveal an accuracy of 94.82% in continuously monitoring glucose variations.

Abstract This study proposes a highly sensitive portable device that utilizes electromagnetic waves and data analytics for instantaneous Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS‐CoV‐2) detection. The device consists of a Radio Frequency (RF) circuit that interprets reflected and transmitted electromagnetic waves to identify virus signatures in physiologically significant matrices, including human saliva and diluted nasopharyngeal swabs. The sensor's accuracy is validated in both pre‐clinical and clinical settings, where clinical measurements demonstrate an instantaneous detection accuracy of 94%, sensitivity of 95%, and specificity of 97.5% between the sensor's physical parameters and SARS‐CoV‐2 detection. The sensor's accurate real‐time response is due to its unique design and precise modeling techniques. In addition, the same sensing system is tested across different viruses and its ability to differentiate between influenza A, respiratory syncytial, and SARS‐CoV‐2 viruses is proven. Hence this work presents a holistic system that can predict the viral concentration of SARS‐CoV‐2, as well as differentiate between different viruses instantaneously and without adding any amplifying agent.

Body-responsive sensing using electromagnetic waves transforms radio frequency-based sensors and medical devices into interactive tools that disseminate the body’s interaction with electromagnetic fields and correlate it with medical diagnostics. This sensing offers non-invasive, real-time insights into the human body, revolutionizing disease detection, continuous monitoring, and personalized healthcare management. Unlike traditional methods often burdened by cost and radiation risk, electromagnetic sensors seamlessly integrated into medical devices like implants, wearables, and imaging equipment, showcase remarkable benefits in biomarker detection, vital signs tracking, and early cancer screening. In this paper, we delve deep into the world of electromagnetic sensors and their applications in healthcare diagnostics. Moreover, we explore the challenges and prospects of these electromagnetic devices, paving the way for their seamless integration into clinical practice.

Advanced Sensor ResearchVolume 3, Issue 4 202470013 Inside Front CoverOpen Access Instantaneous Viral Detection of SARS-CoV-2 and Beyond using Electromagnetic Sensing (Adv. Sensor Res. 4/2024) Rayan Al Sayed Ali, Rayan Al Sayed AliSearch for more papers by this authorNader Shafi, Nader ShafiSearch for more papers by this authorFatima Asadallah, Fatima AsadallahSearch for more papers by this authorRachel Njeim, Rachel NjeimSearch for more papers by this authorHabib Al Kalamouni, Habib Al KalamouniSearch for more papers by this authorHassan Zaraket, Hassan ZaraketSearch for more papers by this authorRouwaida Kanj, Rouwaida KanjSearch for more papers by this authorAssaad Eid, Assaad EidSearch for more papers by this authorJoseph Costantine, Joseph CostantineSearch for more papers by this authorYoussef Tawk, Youssef TawkSearch for more papers by this author Rayan Al Sayed Ali, Rayan Al Sayed AliSearch for more papers by this authorNader Shafi, Nader ShafiSearch for more papers by this authorFatima Asadallah, Fatima AsadallahSearch for more papers by this authorRachel Njeim, Rachel NjeimSearch for more papers by this authorHabib Al Kalamouni, Habib Al KalamouniSearch for more papers by this authorHassan Zaraket, Hassan ZaraketSearch for more papers by this authorRouwaida Kanj, Rouwaida KanjSearch for more papers by this authorAssaad Eid, Assaad EidSearch for more papers by this authorJoseph Costantine, Joseph CostantineSearch for more papers by this authorYoussef Tawk, Youssef TawkSearch for more papers by this author First published: 11 April 2024 https://doi.org/10.1002/adsr.202470013AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Graphical Abstract SARS-CoV-2 Sensing and Detection In article 2300135, Youssef Tawk and co-workers introduce an advanced portable device that leverages electromagnetic waves and data analytics to instantaneously detect and differentiate between the SARS-CoV-2 virus and different respiratory viruses. It employs a radio frequency (RF) circuit to electromagnetically identify virus signatures in diluted nasopharyngeal swabs with a detection accuracy of 94%, a sensitivity of 95%, and a specificity of 97.5%. Volume3, Issue4April 2024202470013 RelatedInformation

C-peptide, a byproduct of insulin synthesis believed to be biologically inert, is emerging as a multifunctional molecule. C-peptide serves an anti-inflammatory and anti-atherogenic role in type 1 diabetes mellitus (T1DM) and early T2DM. C-peptide protects endothelial cells by activating AMP-activated protein kinase α, thus suppressing the activity of NAD(P)H oxidase activity and reducing reactive oxygen species (ROS) generation. It also prevents apoptosis by regulating hyperglycemia-induced p53 upregulation and mitochondrial adaptor p66shc overactivation, as well as reducing caspase-3 activity and promoting expression of B-cell lymphoma-2. Additionally, C-peptide suppresses platelet-derived growth factor (PDGF)-beta receptor and p44/p42 mitogen-activated protein (MAP) kinase phosphorylation to inhibit vascular smooth muscle cells (VSMC) proliferation. It also diminishes leukocyte adhesion by virtue of its capacity to abolish nuclear factor kappa B (NF-kB) signaling, a major pro-inflammatory cascade. Consequently, it is envisaged that supplementation of C-peptide in T1DM might ameliorate or even prevent end-organ damage. In marked contrast, C-peptide increases monocyte recruitment and migration through phosphoinositide 3-kinase (PI-3 kinase)-mediated pathways, induces lipid accumulation via peroxisome proliferator-activated receptor γ upregulation, and stimulates VSMC proliferation and CD4+ lymphocyte migration through Src-kinase and PI-3K dependent pathways. Thus, it promotes atherosclerosis and microvascular damage in late T2DM. Indeed, C-peptide is now contemplated as a potential biomarker for insulin resistance in T2DM and linked to increased coronary artery disease risk. This shift in the understanding of the pathophysiology of diabetes from being a single hormone deficiency to a dual hormone disorder warrants a careful consideration of the role of C-peptide as a unique molecule with promising diagnostic, prognostic, and therapeutic applications.

BackgroundThe effect of gadolinium-based contrast agents (GBCA) on the spinal cord is not established, especially in patients with diabetes mellitus.PurposeTo investigate neuronal and myelin loss in the spinal cord when employing macrocyclic ionic Gadoterate Meglumine (Gd-DOTA) and non-ionic Gadobuterol (Gd-BT-DO3A) GBCA in rats with and without diabetes mellitus.Materials and methodsThis study was performed between November 2018 and February 2020. Sixty young Sprague Dawley white rats (n = 6/group) were given injections of two macrocyclic GBCA: 0.5 mmol/ml Gd-DOTA and 1 mmol/ml Gd-BT-DO3A, using volumes based of the recommended doses (0.1 ml and 0.2 ml) for 42 days in both healthy and diabetic rats. Control groups received saline injections. Morphological assessment of spinal cord tissues was performed on three spinal segments. Neuronal counts in the ventral horns and myelin sparing percentage in the white matter were determined and compared in each group employing one-way ANOVA and Dunnett test for each category followed by three-way factorial analysis.ResultsLow neuronal count and myelin percentage-area were obtained in groups receiving 0.2 ml Gd-DOTA (p = .001;p = .002;p < .001 neurons; and p < .001;p = .007;p = .001 myelin %) and Gd-BT-DO3A (p = .01;p = .048;p = .006 neurons; p < .001;p = .01;p = .001 myelin %). Similarly, neuronal loss was seen in diabetics receiving low volume-injection (0.1 ml) of Gd-DOTA (p = .04;p = .03;p = .42), Gd-BT-DO3A (p = .002;p = .007;p = .01); or high volume-injection (0.2 ml) of Gd-DOTA (p = .001;p = .003;p = .01) or Gd-BT-DO3A (p < .001,p = .002;p = .002), with associated decrease in myelin sparing for each category with low dose Gd-DOTA (p < .001, p = .001; p. = 09),Gd-BT-DO3A (p = .003;p = .003;p = .007); or the higher dose counterparts of Gd-DOTA (p < .001; p < .00; p = .001) and Gd-BT-DO3A (p < .001, p < .001, p < .001).Damage was observed using the standard dose (equivalent of 0.1 mmol/kg for rats) of Gd-DOTA (0.2 ml) but not that of Gd-BT-DO3A (0.1 ml) in healthy rats.ConclusionMultiple high-volume injections of gadoterate meglumine and gadobuterol are associated with neuronal and myelin injury in the spinal cord, more so in rats with diabetes mellitus.