Search Results (111)

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. Coronaviruses are a diverse group of RNA viruses classified into alpha, beta, gamma, and delta genera, with SARS-CoV-2 belonging to the beta-coronavirus family. The virus exhibits high transmissibility and causes a wide spectrum of clinical manifestations ranging from mild respiratory symptoms to severe complications such as acute respiratory distress syndrome, multi-organ failure, and death, particularly among elderly and immunocompromised individuals. Structurally, SARS-CoV-2 possesses a large single-stranded RNA genome encoding major structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, which play critical roles in host-cell recognition and viral infection. Understanding the molecular mechanisms of virus–host interactions, especially protein–protein interactions (PPIs), is essential for uncovering viral pathogenesis and identifying potential therapeutic targets. Traditional experimental techniques for PPI detection, such as yeast two-hybrid and affinity purification methods, are often expensive, labor-intensive, and prone to inaccuracies. Consequently, computational approaches based on machine learning (ML) and deep learning (DL) have gained significant attention for efficient and scalable PPI prediction. These methods use diverse biological information, including protein sequences, structural features, genomic data, Gene Ontology annotations, and interaction networks, to model complex biological relationships. This survey reviews computational approaches to PPI prediction, highlighting ML- and DL-based techniques, methodological advances, performance evaluation practices, and limitations that affect benchmark comparability. It also discusses biological databases and data sources commonly used in PPI studies and explicitly considers how models trained in coronavirus-centered settings may generalize to other viral families with different mechanisms of host interaction. Full article

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection remain a world health problem leading to fibrosis and cirrhosis. Liver damage is primarily mediated by the innate and adaptive immune responses since HBV and HCV are not directly cytotoxic. Kupffer cells and liver-recruited macrophages are heavily implicated in both viral elimination and progression of the disease. HBV and HCV proteins polarize macrophages into either an M1 pro-inflammatory phenotype, promoting hepatocyte damage or into an M2 immunosuppressive phenotype, leading to viral persistence and fibrogenesis via cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). In this review a brief overview of the heterogeneity of liver macrophages in health and during chronic viral infection is presented. Recognition of viruses by macrophages and the modulation of macrophages by viral proteins in the pathogenesis of liver inflammation and injury are discussed in detail. Most importantly, the mechanisms that HBV and HCV are using to manipulate macrophages and escape elimination are also presented. The role of macrophages in the evolution of acute-on-chronic liver failure is analyzed. Finally, a concise presentation of the emerging, but not yet clinically used, therapeutic strategies targeting macrophages to control chronic HBV infection and restore the dysregulated immune response is discussed. In conclusion, this integrated review of liver macrophage implication summarizes the pathophysiology and pathogenesis of HBV and HCV including acute-on-chronic- liver failure and viral cirrhosis. Full article

Background: Carbapenem-resistant K. pneumoniae (CRKP) represents a major challenge in hospitalized patients because of its association with healthcare exposure, restricted antimicrobial options, and adverse clinical outcomes. Microbiological isolation alone does not define invasive disease; therefore, clinical interpretation requires separation of colonization, localized infection, invasive infection, and carbapenem-resistant Enterobacterales (CRE)-associated sepsis. This study evaluated epidemiological features, resistance phenotypes, treatment adequacy, and clinical outcomes among hospitalized adults with K. pneumoniae isolates, using a clinical framework that distinguishes colonization from active infection and invasive disease. Methods: This single-center retrospective observational cohort study included 157 consecutive adults admitted between January and July 2025 to a tertiary-care hospital with at least one microbiologically confirmed K. pneumoniae isolate recovered from clinical specimens and/or CRE surveillance rectal swabs. Isolates were assigned hierarchically to four mutually exclusive phenotypic groups: carbapenem-susceptible K. pneumoniae (CSKP), extended-spectrum beta-lactamase (ESBL)-producing carbapenem-susceptible K. pneumoniae (ESBL), carbapenem-resistant non-carbapenemase-producing K. pneumoniae (CRKP), and carbapenemase-producing K. pneumoniae (CP-KP). A prespecified secondary analysis compared carbapenem-resistant isolates (CRKP + CP-KP) with non-carbapenem-resistant isolates (CSKP + ESBL). Clinical adjudication distinguished colonization-only cases, non-invasive infection, bloodstream infection, device-associated infection, and CRE-associated sepsis; ventilator-associated pneumonia (VAP) was considered when source data allowed reliable attribution. Sepsis was defined according to Sepsis-3 criteria; quick Sequential Organ Failure Assessment (qSOFA) was used only as a bedside screening tool. Statistical tests were selected according to variable type, distribution, and expected cell counts. Results: The cohort comprised 157 unique patients, with a median age of 71 years (interquartile range [IQR], 61–76). Current CRE colonization was documented in 79/154 patients with available colonization status (51.3%). Complete-case in-hospital mortality was higher in the carbapenem-resistant group (CRKP + CP-KP, n = 46) than in the non-carbapenem-resistant group (CSKP + ESBL, n = 111): 11/42 (26.2%) versus 5/108 (4.6%; Fisher exact odds ratio (OR) 7.31, 95% confidence interval (CI) 2.36–22.65; p < 0.001); overall complete-case mortality was 16/150 (10.7%). Multivariable logistic regression for carbapenem resistance (N = 150; five prespecified covariates; events per variable (EPV) = 9.0) identified age 65 years or older (adjusted odds ratio [aOR] 3.78, 95% CI 1.32–10.86), recent hospitalization within 30 days (aOR 2.56, 95% CI 1.16–5.63), and current colonization (aOR 2.96, 95% CI 1.24–7.05) as independent predictors. CRE-associated sepsis was excluded a priori because of definitional circularity with the case definition. Male sex showed a non-significant protective trend (aOR 0.50, 95% CI 0.22–1.12). CRE-associated sepsis showed a strong bivariate association with carbapenem resistance (OR 9.90, 95% CI 3.91–25.09; p < 0.001), and this association is reported descriptively because the variable was excluded from the multivariable model owing to definitional circularity. Model performance was acceptable, with area under the curve (AUC) 0.77, Hosmer–Lemeshow p = 0.95, and Nagelkerke R² = 0.25. Of 99 molecularly characterized isolates, OXA-48-like was detected in 78 (78.8%), NDM in 71 (71.7%), KPC in 6 (6.1%), and NDM + OXA-48-like dual production in 54 (54.5%); VIM and IMP were uniformly negative. Conclusions: In this high-risk hospital cohort, carbapenem resistance in K. pneumoniae was associated with advanced age, recent healthcare exposure, current CRE colonization, and a pronounced unadjusted mortality signal. Interpretation of sepsis and mortality requires explicit separation of colonization from active infection and invasive disease. These findings support intensified CRE surveillance, source-specific clinical interpretation, rapid resistance detection, and risk-adapted empirical antimicrobial strategies in high-risk hospital settings. Full article

Fetal growth restriction (FGR) is frequently defined as the failure of the fetus to reach its genetically predetermined growth potential. Heat shock proteins (HSPs) are extreme-temperature-resistant molecules that help proteostasis. The aim of this prospective case–control immunohistochemistry study is to evaluate the expression of HSP90 and HSP70 in the placentas of pregnancies complicated with FGR and compare their levels with the control placentas of normal-growth pregnancies. A prospective case–control study was conducted including people undergoing singleton pregnancies who gave birth in a tertiary university hospital in Central Greece. Participants were divided into two equal groups: an FGR pregnancy group and a control group with normal growth. Immunohistochemistry of placental samples was assessed using anti-HSP90 alpha/beta antibody (clone F-8, Santa Cruz Biotechnology, Dallas, TX, USA) and anti-HSC70/HSP70 antibody (clone W27, sc-24, Santa Cruz Biotechnology, Dallas, TX, USA). A scoring system was created to quantify the expression of HSP90 and HSP70 in each sample, and the grade of staining was measured at four points. A total of 80 pregnant people were prospectively enrolled in our study, with 40 in each group. Both constitutive (HSP90β and HSC70/HSPA8) and stress-inducible (HSP90α and HSP70/HSPA1A/B) isoforms were analyzed. When comparing the total score of HSP expression, a statistically significant difference was observed for both HSP90 and HSP70. For HSP90 expression, only the Hofbauer cell’s stain was identified as a statistically significant independent factor, meaning that its positive expression was observed in Hofbauer cells. For HSP70 expression, only the staining of syncytiotrophoblasts was identified as an independent factor. FGR is a common pregnancy complication and a leading cause of stillbirth, neonatal mortality, and short- and long-term neonatal morbidity worldwide. Based on our findings, the lower expression levels of both HSP90 and HSP70 are associated with FGR, revealing a possible association with stress response in FGR pathophysiology. However, more robust data from larger-scale prospective studies are needed to elucidate the possible role of HSPs as potential FGR biomarkers. Full article

Several reproductive issues in both men and women are caused by changes in the pulsatile secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). For males to sustain spermatogenesis and Leydig cell function, and for females to ensure orderly folliculogenesis, ovulation, and ovarian steroidogenesis, precise coordination of LH and FSH secretion is necessary. Pituitary responsiveness, the frequency or amplitude of gonadotropin-releasing hormone pulses, or the dysregulation of feedback signals mediated by sex steroids and inhibins all disrupt the balance between LH and FSH secretion. Oligozoospermia, luteal-phase abnormalities, anovulation, or complete spermatogenic failure are possible clinical signs of these alterations. In addition to functional neuroendocrine disturbances, emerging genetic and epigenetic evidence, including pathogenic variants in genes such as gonadotropin-releasing hormone receptor, kisspeptin, kisspeptin receptor, luteinizing hormone beta subunit, follicle-stimulating hormone beta subunit, follicle-stimulating hormone receptor, and luteinizing hormone/choriogonadotropin receptor, has highlighted the role of inherited and acquired molecular defects in disrupting gonadotropin regulation. This narrative review synthesizes contemporary mechanistic, clinical, translational, and genetic evidence elucidating how dysregulated secretion of LH and FSH contributes to reproductive dysfunction. The molecular processes that regulate gonadotropin synthesis and release, as well as neuroendocrine regulation, gene-level determinants of hypothalamic–pituitary–gonadal (HPG) axis dysfunction, and the clinical phenotypes that result from their disruption, are all given special attention. We conclude with a discussion of new treatment strategies that target local intragonadal regulators to enhance gametogenic capacity, modulate gonadotropin signaling, or restore physiological gonadotropin-releasing hormone (GnRH) pulsatility, with consideration of how genetic insights may inform personalized therapeutic approaches. Full article

Peritoneal dialysis (PD)-associated peritonitis in children represents a complex interplay between microbial virulence, host immune activation and progressive peritoneal membrane remodeling. It should not be viewed solely as an acute infectious episode, but as a process unfolding within a chronically conditioned immune environment shaped by prolonged exposure to glucose-based dialysis solutions, oxidative stress and persistent biofilm formation on the Tenckhoff catheter. Mesothelial cells act as immunologically active sentinel cells, recognizing pathogen-associated molecular patterns through Toll-like receptors and related innate pathways. Subsequent activation of nuclear factor kappa B, inflammasome signaling and neutrophil extracellular trap formation further amplifies local inflammatory responses. Repeated inflammatory stimulation promotes mesothelial–mesenchymal transition, angiogenesis and extracellular matrix deposition driven by transforming growth factor beta 1 and interconnected profibrotic networks. In pediatric patients, prolonged PD vintage during critical stages of growth may intensify cumulative structural injury and increase the risk of ultrafiltration failure or encapsulating peritoneal sclerosis. Emerging strategies targeting inflammation, fibrosis and biofilm persistence, together with earlier molecular risk detection, may support preservation of the peritoneal membrane. A unified host–pathogen framework may therefore deepen pathophysiological insight and facilitate more individualized therapeutic strategies in pediatric PD. Full article

The cytotoxic effect of islet amyloid polypeptide (IAPP) misfolding and aggregation has a well-recognized role in the pathogenesis of type 2 diabetes mellitus, mediated by failure of the beta cell’s protein quality control system to rescue the cell from overwhelming proteotoxic stress induced by IAPP aggregates, ultimately leading to apoptosis. A small but growing body of research also links IAPP-mediated proteotoxic stress to the pathogenesis of type 1 diabetes and to the functional decline of transplanted islets. Among the most promising therapeutic approaches under investigation are small organic molecules that may act as direct chemical chaperones to prevent IAPP aggregation, promote the activity of endogenous chaperones, or alter gene networks of the unfolded protein response (UPR) to promote pro-survival rather than pro-apoptotic pathways in response to IAPP-mediated proteotoxic stress. Compounds warranting special attention include 4-phenylbutyrate (PBA), tauroursodeoxycholic acid (TUDCA), and epigallocatechin gallate (EGCG), as each has a growing body of evidence supporting their ability to ameliorate this process, and given that each of these are already known to have good safety profiles in humans, potentially accelerating the timeline to interventional studies. This review explores the evidence for IAPP-mediated proteotoxicity in multiple forms of diabetes, the mechanisms of cytotoxicity at different levels of the cell’s protein quality control systems, how these small organic compounds may act on these processes including new insights on the role of thioredoxin-interacting protein (TXNIP), and the current evidence supporting each of these compounds in mitigating diabetogenesis. Full article

Severe fever with thrombocytopenia syndrome (SFTS) is a newly discovered tick-borne disease caused by SFTS virus (SFTSV) infection. Patients present with high fever, thrombocytopenia, and multiple organ dysfunction, with a high mortality rate and a lack of specific treatment, all of which indicate that research on the deterioration mechanism and treatment of this disease is urgent. Currently, multiple studies have indicated that cytokine storm is one of the core factors contributing to the deterioration of the disease. SFTSV inhibits the host’s type I interferon response through its non-structural protein NSs, thereby promoting immune evasion and viral replication. Extensive viral stimulation leads to dysfunction and abnormal polarization of immune cells (including monocytes, macrophages, dendritic cells, T cells, and B cells), triggering the massive release of pro-inflammatory factors(such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β)), anti-inflammatory factors (such as interleukin-10 (IL-10)), and chemokines(such as interferon-gamma inducible protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8)). This cytokine storm exacerbates the imbalance between pro-inflammatory and anti-inflammatory factors, as well as immune paralysis, leading to vascular endothelial damage, microthrombosis, and ultimately, multi-organ failure, which determines the clinical outcome. Simultaneously, specific cytokines and immune cell phenotypes can serve as biomarkers for disease severity and prognosis. In terms of treatment, this article further summarizes the intervention strategies targeting the aforementioned immune links, including intravenous immunoglobulin (IVIG), tocilizumab (targeting the IL-6 receptor), inhibitors of Janus kinase (JAK) and nuclear factor-kappa B (NF-κB) signaling pathways, interferon, neutralizing antibodies, and other immunotherapy methods. By analyzing the dynamic changes and mechanisms of cytokine storm in the course of SFTS, and summarizing current potential immunotherapy methods, this article aims to provide a theoretical framework for the future treatment of SFTS. Full article

Background/Objectives: The micronutrient iron is closely connected to inflammation and is among the complex factors contributing to beta-cell failure in diabetes. High levels of dietary iron increase the risk of developing type 2 diabetes, and excessive iron uptake by beta-cells can cause oxidative stress and inhibit function. Elevated levels of proinflammatory cytokines in obese individuals, such as interleukin (IL)-1beta and IL-6, increase the risk of developing type 2 diabetes, and there is evidence that these low levels of circulating cytokines can lead to islet dysfunction. Methods: In this study, gene microarray and other data were analyzed for expression differences in islets treated for 48 h with 10 pg/mL IL-1beta + 20 pg/mL IL-6 as a model of low-grade inflammation versus untreated. Results: Three iron-associated genes were among the most cytokine-sensitive in the mouse genome: Hamp, Steap4, and Lcn2. These proteins are all involved with increasing/retaining cellular iron. We hypothesized that increased cellular iron would lead to increased susceptibility to ferroptosis. Surprisingly, 24 h pre-exposure to low-grade inflammation, which upregulates this iron-gene network, prevented subsequent erastin-induced ferroptosis. We also found that Steap4 overexpression reduced islet dysfunction caused by high-dose proinflammatory cytokines (10× low-dose), suggesting an overall protective effect. Steap4 overexpression also upregulated Hamp and Lcn2, suggesting Steap4 regulates these cytokine-sensitive iron genes.; in contrast, ferritin and ferroportin gene expression, which are not sensitive to cytokines, were unchanged. Conclusions: These data suggest an inflammation-induced network of genes involved in cellular iron uptake and retention plays a protective role in islets against oxidative stress and ferroptosis. Full article

Autoimmune type 1 diabetes (T1D) results from the failure of the physiologic regulatory mechanisms that are designed to maintain immune tolerance to pancreatic beta cells. Consequently, the design of strategies to restore tolerance to beta cell antigens is an attractive objective of translational research. We have designed ultrasmall nanoparticles (NPs) loaded with a proinsulin (PI) fusion protein and an agonist for the aryl hydrocarbon receptor (AhR), a transcription factor promoting tolerance induction by different immune cells. We report that a 4 week-treatment with these NPs in non-obese diabetic (NOD) mice starting at disease onset induces temporary and sometimes durable disease remission. Mechanistically, short-term NP treatment induces a rapid depletion of islet infiltrates with a dramatic reduction in the number of CD8⁺ T cells and dendritic cells. This is accompanied by the emergence of B lymphocytes producing IL-10. In the rare mice that undergo durable disease remission, the disappearance of islet infiltrates is associated with the emergence of Foxp3⁺ CD4⁺ regulatory T cells, IFN-γ-producing memory T cells in the spleen, and draining lymph nodes (LNs). We conclude that treatment with these NPs could be of interest in the treatment of recent-onset autoimmune diabetes, but is unlikely to be sufficient for the induction of long-term remission as a stand-alone therapy. Full article

Post-translational modifications (PTMs) provide an integrated regulatory layer that couples nutrient and hormonal signals to whole-body energy homeostasis across metabolic organs. PTMs modulate protein activity, localization, stability, and metabolic networks in a tissue- and state-specific manner. Through network remodeling, PTMs integrate receptor signaling with chromatin and organelle function and align transcriptional control with mitochondrial function, proteostasis, and membrane trafficking. PTM crosstalk connects kinase cascades, nutrient-sensing pathways, and ubiquitin-family modifiers to orchestrate gluconeogenesis, lipolysis, glucose uptake, thermogenesis, and insulin secretion in response to nutrient cues. The metabolic state regulates PTM enzymes through changes in cofactors, redox tone, and compartmentalization, and PTM-dependent changes in transcription and signaling feedback to metabolic tone. In obesity and diabetes, dysregulated post translational modification networks disrupt insulin receptor signaling, disturb organelle quality control, and impair beta cell function, which promotes insulin resistance and beta cell failure. Consequently, PTMs organize metabolic information flow and modulate tissue responses to overnutrition and metabolic stress. A systems-level understanding of PTMs clarifies mechanisms of whole-body energy homeostasis and supports the discovery of new therapeutic targets in metabolic disease. Full article

Spinal health depends on the dynamic interplay between mechanical forces, biochemical signaling, and cellular behavior. This review explores how key molecular pathways, including integrin, yeas-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), Piezo, and Wingless/Integrated (Wnt) with β-catenin, actively shape the structural and functional integrity of spinal tissues. These signaling mechanisms respond to physical cues and interact with inflammatory mediators such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), driving changes that lead to disc degeneration, vertebral fractures, spinal cord injury, and ligament failure. New research is emerging that shows scaffold designs that can directly harness these pathways. Further, new stem cell-based therapies have been shown to promote disc regeneration through targeted differentiation and paracrine signaling. Interestingly, many novel bone and ligament scaffolds are modulating anti-inflammatory signals to enhance tissue repair and integration, as well as prevent scaffold degradation. Neural scaffolds are also arising. These mimic spinal biomechanics and activate Piezo signaling to guide axonal growth and restore motor function. Scientists have begun combining these biological platforms with brain–computer interface technology to restore movement and sensory feedback in patients with severe spinal damage. Although this technology is not fully clinically ready, this field is advancing rapidly. As implantable technology can now mimic physiological processes, molecular signaling, biomechanical design, and neurotechnology opens new possibilities for restoring spinal function and improving the quality of life for individuals with spinal disorders. Full article

Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, such as in metabolic dysfunction-associated steatohepatitis (MASH), idiopathic pulmonary fibrosis (IPF), chronic kidney disease (CKD), and myocardial fibrosis, which can lead to heart failure, cystic fibrosis, and fibrosis in pancreatic tumors, to name a few. MASH is a progressive inflammatory and fibrotic liver condition that has reached pandemic proportions, now considered the largest non-viral contributor to the need for liver transplantation. Methods: We previously studied Oxy210, an anti-fibrotic and anti-inflammatory, orally bioavailable, oxysterol-based drug candidate for MASH, using APOE*3-Leiden.CETP mice, a humanized hyperlipidemic mouse model that closely recapitulates the hallmarks of human MASH. In this model, treatment of mice with Oxy210 for 16 weeks caused significant amelioration of the disease, evidenced by reduced hepatic inflammation, lipid deposition, and fibrosis, atherosclerosis and adipose tissue inflammation. Results: Here we demonstrate increased hepatic expression of senescence-associated genes and senescence-associated secretory phenotype (SASP), correlated with the expression of pro-fibrotic and pro-inflammatorygenes in these mice during the development of MASH that are significantly inhibited by Oxy210. Using the HepG2 human hepatocyte cell line, we demonstrate the induced expression of senescent-associated genes and SASP by TGF-β and inhibition by Oxy210. Conclusions: These findings further support the potential therapeutic effects of Oxy210 mediated in part through inhibition of senescence-driven hepatic fibrosis and inflammation in MASH and perhaps in other senescence-associated fibrotic diseases. Full article

Loop diuretics like furosemide are commonly used in heart failure (HF) treatment, but their effects on disease progression are still unclear. Furosemide treatment accelerates HF deterioration in a swine model, but the mechanism of acceleration is poorly understood. We hypothesized that furosemide activates inflammatory signaling in the failing left ventricular (LV) myocardium, leading to adverse remodeling of the extracellular matrix (ECM). A total of 14 Yorkshire pigs underwent permanent transvenous pacemaker implantation and were paced at 200 beats per minute; 9 non-instrumented pigs provided controls. Seven paced animals received normal saline, and seven received furosemide at a dose of 1 mg/kg intramuscularly. Weekly echocardiograms were performed. Furosemide-treated animals reached the HF endpoint a mean of 3.2 days sooner than saline-treated controls (mean 28.9 ± 3.8 SEM for furosemide and 32.1 ± 2.5 SEM for saline). The inflammatory signaling protein transforming growth factor-beta (TGF-β) and its downstream proteins were significantly (p ≤ 0.05) elevated in the LV after furosemide treatment. The regulatory factors in cell proliferation, mitogen-activated protein kinase signaling pathway proteins, and matrix metalloproteinases were elevated in the furosemide-treated animals (p ≤ 0.05). Our data showed that furosemide treatment increased ECM remodeling and myocardial fibrosis, reflecting increased TGF-β signaling factors, supporting prior results showing worsened HF. Full article

Several studies showed that the incidence of Alzheimer’s disease (AD) is significantly lower in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical bacillus Calmette–Guérin (BCG) instillations compared to treatment by alternative methods. Hypothetically, failure to clear misfolded and aggregated proteins (i.e., beta-amyloid) in AD brains and peripheral blood mononuclear cells (PBMCs) implicates BCG in upgrading the unfolded protein response (UPR). To test this hypothesis, pre- versus post-BCG PBMC proteins of the UPR pathway were compared in six NMIBC patients by capillary immunoelectrophoresis on an Abby instrument. PERK, the endoplasmic reticulum (ER) resident kinase, a stress-activated sensor, and its substrate alpha component of the eIF2 translation factor (eIF2a) complex inactivation were considered as potentially proapoptotic via a downstream proapoptotic transcription factor only if persistently high. GAPDH, a glycolytic marker of innate immunocyte training by BCG, and eight other UPR proteins were considered antiapoptotic. Summation of antiapoptotic %change scores per patient showed that the older the age, the lower the antiapoptotic %change. Higher antiapoptotic scores were observed upon a longer time from BCG treatment (with the exception of the patient in her ninth decade of life). Studies with more individuals could substantiate that BCG enhances the antiapoptotic aggregate-clearance effect of the UPR in PBMCs of NMIBC patients, which hypothetically protects brain cells against AD. Full article