Search Results (205)

Obesity is a global health crisis with profound implications for cancer risk, particularly within the gastrointestinal (GI) tract. Mounting evidence demonstrates that excess adiposity contributes to the initiation, progression, and poor outcomes of GI malignancies through a constellation of interrelated mechanisms. This review comprehensively examines the biologic pathways linking obesity to cancers of the esophagus, stomach, colon, liver, pancreas, and gallbladder. Chronic low-grade inflammation, driven by adipose tissue-derived cytokines and immune cell infiltration, plays a central role in tumorigenesis via the activation of NF-κB, STAT3, and other pro-oncogenic signaling cascades. Hyperinsulinemia and insulin resistance increase mitogenic IGF-1 signaling, while dysregulated adipokines, particularly elevated leptin and reduced adiponectin, promote cellular proliferation and impair tumor suppression. Dysbiosis of the gut microbiome and alterations in bile acid metabolism generate carcinogenic metabolites that contribute to DNA damage and immune evasion. Additionally, obesity-induced tissue hypoxia fosters tumor growth through HIF-1α-mediated pathways. We further highlight organ-specific associations, such as visceral adiposity’s role in Barrett’s esophagus and hepatocellular carcinoma emerging from metabolic dysfunction-associated steatotic liver disease (MASLD). Importantly, emerging data suggest that weight loss, achieved via lifestyle, pharmacologic, or surgical interventions, may mitigate these carcinogenic pathways and improve tumor biology. As obesity prevalence continues to rise globally, elucidating its mechanistic ties to GI malignancies is essential for risk stratification, prevention strategies, and personalized care. By integrating epidemiologic and molecular insights, this review underscores the need for multidisciplinary approaches to curb the oncogenic burden of obesity and improve outcomes in GI oncology. Full article

Scarring is a prevalent and often undesirable outcome of the wound healing process, impacting millions worldwide. The complex and dynamic nature of wound healing, including hemostasis, inflammation, proliferation, and remodeling, necessitates precise, making it hard for stage-specific interventions to prevent pathological scarring. This study introduces a double-layer hydrogel system designed for sequential drug release, aligning with the stage-specific need for wound healing. The lower layer, containing curcumin-loaded chitosan nanoparticles, shows early anti-inflammatory and antioxidant effects, while the upper layer, with pirfenidone-encapsulated gelatin microspheres, presents late-stage anti-fibrotic activity. The hydrogel’s unique design, with varying degradation rates and mechanical properties in each layer, facilitates cascade drug release in synchrony with wound healing stages. Rapid release of curcumin from the lower layer promotes proliferation by mitigating inflammation and oxidative stress, while the sustained release of pirfenidone from the upper layer inhibits excessive fibrillation during late proliferation and remodeling. In a rat model of full-thickness skin defect, treatment with a double-layer hydrogel drug delivery system accelerated the wound closure, improved scar quality, and promoted the formation of hair follicles. Therefore, this innovative approach lays a promising foundation for future clinical applications in anti-scar therapies, offering a significant advancement in wound care and regenerative medicine. Full article

Background & Objectives: Targeted-release budesonide (TRB) is the first approved agent aimed at targeting the early pathogenetic cascade in IgA nephropathy (IgAN). Materials and Methods: This prospective study included Caucasian IgAN patients diagnosed within the last 5 years, who had started a 10-month TRB treatment and were followed in the outpatient clinic. All participants had been on the maximal supportive care dose for at least the previous 6 months. Kidney function and proteinuria levels were recorded at the start of TRB treatment (T0) and at 3, 6, and 10 months (T3, T6, and T10, respectively), while urinary monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and clusterin (CLU) levels were measured at T0 and T3. Results: In the cohort of all patients (mean age 53.24 ± 12.76 years, estimated glomerular filtration rate (eGFR 52.84 ± 25.93 mL/min/1.73 m², proteinuria 2.84 ± 1.26 g/24 h), significant correlations were observed at T0 between MMP-9 and MCP-1 (r = 0.74, p = 0.004), MMP-9 and uCLU (r = 0.77, p = 0.002), and MCP-1 and uCLU (r = 0.65, p = 0.01). At T3, a significant correlation between MMP-9 and urinary CLU (uCLU) persisted (r = 0.71, p = 0.03). Higher MCP-1 (r = −0.560, p = 0.046) and MMP-9 (r = −0.330, p = 0.012) levels at T0 were associated with reduced proteinuria. Conversely, increased clusterin at T3 (r = 0.599, p = 0.031) was associated with worsening proteinuria. Conclusions: The treatment response to TRB was heterogeneous, with recent diagnosis (RD) patients showing improved kidney function and proteinuria, while older diagnosis (OD) patients exhibited worsening biomarkers and declining kidney function. Therefore, early interventions are crucial in IgAN patients. Finally, the biomarkers studied can be used prognostically to monitor disease progression. Full article

Despite significant advancements in medical and surgical care, the morbidity and mortality rates of neonates and infants undergoing congenital cardiac surgery remain high. To identify new pathomechanisms associated with postoperative organ dysfunction, extracellular vesicles (EVs) were isolated from plasma from neonates and infants with or without organ dysfunction at three different time points around congenital cardiac surgery, and the EV miRNA expression profiles in the plasma were analyzed. A clear distinction was observed between the organ dysfunction (OD) and non-organ dysfunction (NOD) groups based on their EV miRNA expression profiles. Apoptosis and proinflammatory pathways were consistently upregulated across all time points in the OD group. Complement and coagulation cascades unexpectedly displayed downregulation at the end of the surgery in the OD group, which was verified further at the proteomic level in an independent patient cohort. The neutrophil extracellular trap (NET) formation was enhanced in the OD group across all time points compared to that in the NOD group. As NETs are known to consume complement components, these observed events might be interconnected. A feature selection machine learning method identified miR-200b-5p, miR-4800-5p, miR-363-3p, and miR-483-5p as robustly linked to organ dysfunction following congenital cardiac surgery (accuracy score = 9; SD in accuracy = 0.3162). In conclusion, our study suggested that neonates and infants with postoperative organ dysfunction were associated with enhanced NET formation and complement consumption. Full article

Coagulation testing is commonly used in the intensive care unit (ICU) to monitor and manage the hemostatic balance, assess bleeding risk, and guide anticoagulant therapy. Routine tests used for this purpose include prothrombin time, activated partial thromboplastin time, fibrinogen, and anti-Xa assays. Some of the drugs commonly used in critically ill patients may influence coagulation assays by interacting in vitro with reagents or in vivo with coagulation pathways, thus altering the coagulation cascade and the fibrinolytic pathway. While the pharmacological effects of drugs on coagulation are usually documented, to our knowledge, no comprehensive review article has been published to date. In this review, we have conducted a critical analysis of the literature to define: (1) the impact of hydroxocobalamin, intravenous lipid emulsion, and propofol on chromogenic assays; (2) the impact of PEGylated compounds, emicizumab, recombinant activated factor VII, antibiotics, and sugammadex on chronometric assays; (3) the challenges associated with bridging anticoagulation in the ICU as well as the effect of N-acetylcystein, serotonin reuptake inhibitors, and tramadol on the hemostasis system. For each drug, we specify the routine coagulation assay that is impacted, whether this is linked to an in vitro interference or an in vivo effect, and the potential consequences on patient management. Full article

The impacts of COVID-19 among men who have sex with men (MSM), who face limited access to HIV services due to stigma, discrimination, and violence, need to be assessed and quantified in terms of HIV treatment outcomes for future pandemic preparedness. This study aimed to evaluate the effects of the COVID-19 lockdown on the HIV treatment cascade among MSM in selected provinces of South Africa using routine programme data after the implementation of differentiated service delivery (DSD) models. An interrupted time series analysis was employed to observe the trends and patterns of HIV treatment outcomes among MSM in Gauteng, Mpumalanga, and KwaZulu-Natal from 1 January 2018 to 31 December 2022. Interrupted time series analysis was applied to quantify changes in the accessibility and utilisation of HIV treatment services using the R software version 4.4.1. The segmented regression models showed a decrease followed by an upward trend in all HIV treatment outcomes. After the implementation of the DSD model, significant increases in positive HIV tests (estimate = 0.001572; p < 0.001), linkage to HIV care (estimate = 0.001486; p < 0.001), ART initiations (estimate = 0.001003; p = 0.004), ART collection (estimate = 0.001748; p < 0.001), and taking viral load tests (estimate = 0.001109; p = 0.001) were observed. There was an overall increase in all HIV treatment outcomes during the COVID-19 lockdown in light of the DSD model. Full article

Glioblastomas (GBMs), among the most aggressive and resilient brain tumors, characteristically exhibit high angiogenic potential, leading to the formation of a dense yet aberrant vasculature, both morphologically and functionally. With these premises, numerous expectations were initially placed on anti-angiogenic therapies, soon dashed by their limited efficacy in concretely improving patient outcomes. Neovascularization in GBM soon emerged as a complex, dynamic, and heterogeneous process, hard to manage with the classical standard of care. Growing evidence has revealed the existence of numerous non-canonical strategies of angiogenesis, variously exploited by GBM to meet its ever-increasing metabolic demand and differently involved in tumor progression, recurrence, and escape from treatments. In this review, we provide an accurate description of each neovascularization mode encountered in GBM tumors to date, highlighting the molecular players and signaling cascades primarily involved. We also detail the key architectural and functional aspects characteristic of the GBM vascular compartment because of an intricate crosstalk between the different angiogenic networks. Additionally, we explore the repertoire of emerging therapies against GBM that are currently under study, concluding with a question: faced with such a challenging scenario, could combined therapies, tailored to the patient’s genetic signatures, represent an effective game changer? Full article

Background: Sickle cell disease (SCD) is consequently associated with increased rates of infant and childhood morbidity and mortality. Therefore, early detection is a crucial aspect of managing SCD to mitigate complications and improve health outcomes for SCD children. Neonatal screening is the primary method for identifying newborns with SCD, enabling early diagnosis, family screening, and comprehensive medical care. The protocol presented in this paper describes a study aimed at screening newborns for SCD in high-prevalence SCD states of India to understand the magnitude of the problem and the benefits of early comprehensive care along with the genotypic and phenotypic correlation. Methods: A prospective cohort study will be conducted across seven sites in six states of India (Rajasthan, Odisha, Tamil Nadu, Maharashtra, Madhya Pradesh, and Gujarat), having a high prevalence of SCD. The cord blood or heel prick samples of all the live-born babies delivered within the facilities of selected regions will be collected for screening SCD by HPLC (High-Performance Liquid Chromatography). All the sickle cell homozygous (SS) babies will be confirmed at 6 weeks for Sickle genotype along with cascade screening. Further, SS babies will be followed up from six weeks up to five years of life with initiation of folic acid, antibiotic prophylaxis, and hydroxyurea treatment at appropriate times. Results: The protocol aims to lay the groundwork for the smooth implementation of newborn screening programs and effective follow-up strategies. Conclusions: It will pave the way for developing a strategic framework for implementing newborn screening programs for haemoglobinopathies in India. Full article

The use of autologous biological preparations (ABPs) and their combinations fills the void in healthcare treatment options that exists between surgical procedures, like plastic reconstructive, cosmetic, and orthopedic surgeries; non-surgical musculoskeletal biological procedures; and current pharmaceutical treatments. ABPs, including high-density platelet-rich plasma (HD-PRP), bone marrow aspirate concentrates (BMACs), and adipose tissue preparations, with their unique stromal vascular fractions (SVFs), can play important roles in tissue regeneration and repair processes. They can be easily and safely prepared at the point of care. Healthcare professionals can employ ABPs to mimic the classical wound healing cascade, initiate the angiogenesis cascade, and induce tissue regenerative pathways, aiming to restore the integrity and function of damaged tissues. In this review, we will address combining autologous HD-PRP with adipose tissue, in particular the tissue stromal vascular fraction (t-SVF), as we believe that this biocellular combination demonstrates a synergistic effect, where the HD-PRP constituents enhance the regenerative potential of t-SVF and its adipose-derived mesenchymal stem cells (AD-MSCs) and pericytes, leading to improved functional tissue repair, tissue regeneration, and wound healing in variety of clinical applications. We will address some relevant platelet bio-physiological aspects, since these properties contribute to the synergistic effects of combining HD-PRP with t-SVF, promoting overall better outcomes in chronic inflammatory conditions, soft tissue repair, and tissue rejuvenation. Full article

Background: Awareness, diagnosis, and treatment of familial hypercholesterolemia (FH) starting from childhood are a cornerstone of cardiovascular disease prevention. The LIPIGEN Paediatric Group, a network of specialised centres for the diagnosis and management of familial genetic dyslipidemia, is an active part of this mission. Materials and Methods: This is the second exploratory survey organised within the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) paediatric centres. A digital questionnaire consisting of 16 questions was proposed to the principal investigators of 35 LIPIGEN centres in September 2023. We analysed the main FH screening strategies implemented in Italy, which are the referral characteristics to the lipid clinics and clinical and biochemical criteria considered to diagnose FH in paediatric patients. Results: Centres frequently reported conducting cascade screening (88.6%) and reverse screening (57.1%), whereas 28.6% of respondents indicated using selective screening and only 5.7% reported employing child–parent screening. We documented a detailed biochemical characterisation of paediatric patients (62.9% of respondents usually perform full lipoprotein profile and 80% determine lipoprotein(a) for each patient) and a high percentage of genetic analysis (82.9%). We have also highlighted a quite low awareness of FH as a genetic condition involving paediatric patients among primary care paediatricians and general practitioners. Conclusions: The results of our survey show that specialised lipid centres usually have good diagnostic competence when dealing with paediatric patients with hypercholesterolemia. However, FH awareness and the importance of early diagnosis and treatment initiation in childhood still need to be further improved. Full article

Background/Objectives: Spinal cord injury (SCI) is a complex medical condition with widespread effects that extend beyond motor and sensory impairments. In addition to nervous system damage, SCI patients experience various secondary complications, including vascular dysfunction, altered body composition, and metabolic disturbances. Among the most common secondary pathologies is the development of pressure injuries (PIs), chronic wounds that significantly affect quality of life and can be challenging to treat. Understanding the physiological and cellular mechanisms behind these complications is crucial for improving care and therapeutic outcomes. Methods: We conducted a comprehensive literature search in PubMed, Scopus, and Google Scholar using keywords related to spinal cord injury, pressure ulcer/pressure injuries, metabolic and vascular dysfunction, biomechanics, and regenerative therapies. Studies were selected based on their relevance to the pathophysiology, risk factors, and novel therapeutic approaches for PIs in SCI patients. Results: Vascular dysfunction, characterized by impaired blood flow and microcirculatory issues, predisposes SCI patients to ischemia and tissue necrosis, particularly in areas subjected to prolonged pressure. Additionally, changes in body composition, such as increased adiposity and muscle atrophy, further compromise tissue integrity and healing capacity. The inflammatory response, mediated by cytokines such as IL-1, IL-6, and TNF-α, exacerbates these effects by sustaining a pro-inflammatory environment that delays the transition of macrophages to the M2 phenotype, critical for wound healing. External factors, such as poor nutrition, infections, and immobility, also play a significant role in worsening the wound healing process. Conclusions: Chronic SCI induces a cascade of physiological changes that predispose patients to the development of PIs and complicate their recovery. The intricate interplay of vascular, metabolic, and inflammatory responses creates a hostile environment for wound healing. A deeper understanding of these systemic effects is essential not only for developing targeted therapeutic strategies to improve chronic wound healing but also for refining preventive approaches that minimize their occurrence. Advancing this knowledge will ultimately help enhance the quality of life for individuals with SCI. Full article

Mucociliary clearance, the ability of the respiratory tract to protect the integrity of the airways through the mechanical removal of potentially harmful substances, is of enormous importance during intensive care treatment. The present study aimed to evaluate the influence of clinically relevant inotropic agents on mucociliary clearance. The particle transport velocity (PTV) of isolated murine tracheae was measured as a surrogate for mucociliary clearance in the presence of dobutamine, epinephrine, and milrinone. Inhibitory substances were applied to elucidate the signal transduction cascades and the value and origin of calcium ions which provoke alterations in mucociliary clearance function. Dobutamine, epinephrine, and milrinone increased the PTV in a dose-dependent manner with half maximal effective concentrations of 75.7 nM, 87.0 nM, and 13.7 µM, respectively. After the depletion of intracellular calcium stores, no increase in PTV was observed after administering any of the three inotropic agents. While dobutamine and epinephrine activated β-adrenergic receptors, epinephrine used both the phospholipase C (PLC) and protein kinase A (PKA) pathway to promote the release of intracellular Ca²⁺. However, dobutamine primarily acted on the PKA pathway, having only a minor influence on the PLC pathway. The induced changes in PTV following milrinone administration required both the PKA and PLC pathway, although the PKA pathway was responsible for most of the induced changes. In conclusion, the common inotropic agents dobutamine, epinephrine, and milrinone increase murine PTV in a concentration-dependent manner and ultimately release Ca²⁺ from intracellular calcium stores, suggesting the function of changes in mucociliary clearance in the respiratory tract. Full article

Aneurysmal subarachnoid hemorrhage (SAH) involves a significant influx of blood into the cerebrospinal fluid, representing a severe form of stroke. Despite advancements in aneurysm closure and neuro-intensive care, outcomes remain impaired due to cerebral vasospasm and delayed cerebral ischemia (DCI). Previous pharmacological therapies have not successfully reduced DCI while improving overall outcomes. As a result, significant efforts are underway to better understand the cellular and molecular mechanisms involved. This review focuses on the activation and effects of immune cells after SAH and their interactions with neurotoxic and vasoactive substances as well as inflammatory mediators. Particular attention is given to clinical studies highlighting the roles of natural killer (NK) cells and regulatory T cells (Treg) cells. Alongside microglia, astrocytes, and oligodendrocytes, NK cells and Treg cells are key contributors to the inflammatory cascade following SAH. Their involvement in modulating the neuro-inflammatory response, vasospasm, and DCI underscores their potential as therapeutic targets and prognostic markers in the post-SAH recovery process. We conducted a systematic review on T cell- and natural killer cell-mediated inflammation and their roles in cerebral vasospasm and delayed cerebral ischemia. We conducted a meta-analysis to evaluate outcomes and mortality in studies focused on NK cell- and T cell-mediated mechanisms. Full article

In the era where digital technologies are becoming increasingly prevalent, it is anticipated that a majority of the global population will have at least a basic understanding of informatics. However, empirical evidence suggests that a significant portion of the global population remains digitally illiterate. This phenomenon is particularly pronounced in the case of the senior adult population. In light of the aforementioned challenges, this work integrates Computer Science Unplugged exercises, based on games and recreational activities without the use of computers, and L2T2L, a learning-by-teaching methodology whereby university students learn and then, in turn, teach that learning to other populations in a cascading manner. A case study was conducted in Lima, Peru, with the participation of 140 volunteers from centres for the elderly. Thirty-five students and one teacher from the Universidad Científica del Sur were responsible for initiating the transfer of knowledge from the university to the senior citizens, with the assistance of twelve individuals responsible for their care. The results demonstrate that the participants attained a commendable level of comprehension when attempting to complete all of the assigned tasks. Furthermore, the efficacy of L2T2L is evident in its adaptability and suitability for scenarios beyond those for which it was originally designed. Full article

Impedance-based biosensing has emerged as a critical technology for high-sensitivity biomolecular detection, yet traditional approaches often rely on bulky, costly impedance analyzers, limiting their portability and usability in point-of-care applications. Addressing these limitations, this paper proposes an advanced biosensing system integrating a Silicon Nanowire Field-Effect Transistor (SiNW-FET) biosensor with a high-gain amplification circuit and a 1D Convolutional Neural Network (CNN) implemented on FPGA hardware. This attempt combines SiNW-FET biosensing technology with FPGA-implemented deep learning noise reduction, creating a compact system capable of real-time viral detection with minimal computational latency. The integration of a 1D CNN model on FPGA hardware for adaptive, non-linear noise filtering sets this design apart from conventional filtering approaches by achieving high accuracy and low power consumption in a portable format. This integration of SiNW-FET with FPGA-based CNN noise reduction offers a unique approach, as prior noise reduction techniques for biosensors typically rely on linear filtering or digital smoothing, which lack adaptive capabilities for complex, non-linear noise patterns. By introducing the 1D CNN on FPGA, this architecture enables real-time, high-fidelity noise reduction, preserving critical signal characteristics without compromising processing speed. Notably, the findings presented in this work are based exclusively on comprehensive simulations using COMSOL and MATLAB, as no physical prototypes or biomarker detection experiments were conducted. The SiNW-FET biosensor, functionalized with antibodies specific to viral antigens, detects impedance shifts caused by antibody–antigen interactions, providing a highly sensitive platform for viral detection. A high-gain folded-cascade amplifier enhances the Signal-to-Noise Ratio (SNR) to approximately 70 dB, verified through COMSOL and MATLAB simulations. Additionally, a 1D CNN model is employed for adaptive noise reduction, filtering out non-linear noise patterns and achieving an approximate 75% noise reduction across a broad frequency range. The CNN model, implemented on an Altera DE2 FPGA, enables high-throughput, low-latency signal processing, making the system viable for real-time applications. Performance evaluations confirmed the proposed system’s capability to enhance the SNR significantly while maintaining a compact and energy-efficient design suitable for portable diagnostics. This integrated architecture thus provides a powerful solution for high-precision, real-time viral detection, and continuous health monitoring, advancing the role of biosensors in accessible point-of-care diagnostics. Full article