Stress responses can impact bladder cancer (BC) outcomes via immune–inflammatory pathway modulation. This study explores heart rate variability (HRV) associations with serum immune–inflammatory biomarkers, blood count inflammatory markers, and psychosocial self-report measures in patients versus healthy controls. The TREM-1 and TREM-2 expressions on peripheral blood monocytes were analysed via flow cytometry; serum inflammatory biomarkers by ELISA; HRV (5-min ECG) pre-tumour resection; blood counts by haematology analyser; and psychosocial factors by validated questionnaires. Patients exhibited altered immune–inflammatory profiles with increased TREM-1/TREM-2, sTREM-1, sTREM-1/sTREM-2 ratio, BDNF, MCP-1, and NLR, and reduced IFN-γ, IL-10, LMR, and PMR. HRV analysis indicated sympathetic dominance (SNS, Stress indices, ACmod) and reduced parasympathetic modulation (PNS index, SDNN, RMSSD, 2UV%, DCmod, SD1). Sympathetic HRV indices correlated positively with sTREM-1, sTREM-1/sTREM-2 ratio, fractalkine, and inflammatory markers (SII, NLR, PLR) and negatively with parasympathetic HRV indices—correlations absent in controls. Only in patients, reduced physical function and social support, and higher anxiety, depression, and fatigue, associated positively with sympathetic HRV indices and inflammatory markers. This study links immune–inflammatory markers, HRV parameters, and psychosocial factors in BC, suggesting that immune and autonomic variations may relate to unfavourable outcomes. Incorporating these assessments could help tailor more personalised treatment strategies for BC patients.

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterised by progressive loss of memory. In the AD brain, matrix metalloproteinases (MMPs) are involved in the disruption of the blood-brain barrier resulting in a neuroinflammatory response. The objective of our investigation was to assess the association of MMP2 rs243866 and rs2285053 polymorphisms with susceptibility to AD, to assess the interaction of MMP2 variants with APOE ε4 risk allele, and to evaluate their influence on the age at disease onset and MoCA score. A total of 215 late-onset AD patients and 373 control subjects from Slovakia were genotyped for MMP2 rs243866 and rs2285053 polymorphisms. The MMP2 association with AD risk and clinical parameters was evaluated by logistic and linear regression analyses. No statistically significant differences in either MMP2 rs243866 and rs2285053 allele or genotype frequencies between AD patients and the control group have been observed (p > 0.05). However, the correlation with clinical findings revealed a higher age at disease onset in MMP2 rs243866 GG carriers in the dominant model as compared to other MMP2 genotype carriers (p = 0.024). Our results suggest that MMP2 rs243866 promoter polymorphism may have an impact on the age at AD onset in the patients.

The correlation between pancreatic ductal adenocarcinoma (PDAC) and diabetes-related mechanisms support the hypothesis that early therapeutic strategies targeting diabetes can contribute to PDAC risk reduction and treatment improvement. A systematic review was conducted, using PubMed, Embase and Cochrane Library databases, to evaluate the current evidence from clinical studies qualitatively examining the efficacy of four natural products: Curcumin—Curcuma longa L.; Thymoquinone—Nigella sativa L.; Genistein—Glycine max L.; Ginkgo biloba L.; and a low-carbohydrate ketogenic diet in type 2 diabetes (T2D) and PDAC treatment. A total of 28 clinical studies were included, showing strong evidence of inter-study heterogeneity. Used as a monotherapy or in combination with chemo-radiotherapy, the studied substances did not significantly improve the treatment response of PDAC patients. However, pronounced therapeutic efficacy was confirmed in T2D. The natural products and low-carbohydrate ketogenic diet, combined with the standard drugs, have the potential to improve T2D treatment and thus potentially reduce the risk of cancer development and improve multiple biological parameters in PDAC patients.

Background: Human leukocyte antigen G (HLA-G) is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities. It belongs to class I non-classical major histocompatibility complex molecules and has been upregulated in various cancer types. In bladder cancer (BC) tumors, the association of HLA-G with cancer progression has to be explained. Methods: A total of 89 BC patients and 74 control subjects were genotyped for the HLA-G 14 bp ins/del polymorphism. In urine cell samples, HLA-G mRNA expression was analyzed using real-time PCR. Soluble HLA-G (sHLA-G) serum levels were measured by ELISA. The associations between the HLA-G 14 bp ins/del polymorphism, HLA-G mRNA expression, and/or sHLA-G levels and selected variables including tumor grade, disease stage, body mass index, and heart rate variability (HRV) parameters were evaluated. Results: The protective HLA-G 14 bp ins/ins genotype under the recessive genetic model was associated with lower HLA-G mRNA expression in the BC group (p = 0.049). Significantly higher HLA-G mRNA expression was detected in patients with pT2 + pT3 as compared to those with pTa + pT1 stages (p = 0.0436). Furthermore, higher HLA-G mRNA expression was observed in high-grade muscle-infiltrating BC (MIBC) than in the low-grade non-MIBC group (p = 0.0365). Patients with a level of sHLA-G above 29 U/mL had shorter disease-free survival than patients with lower sHLA-G levels. Furthermore, the opposite HRV correlations with sHLA-G levels in BC patients as compared to controls probably reflect the different roles of HLA-G in health and cancer. Conclusions: Our results suggest the impact of the HLA-G 14 bp ins/del variant, HLA-G expression, and autonomic nervous system imbalance on advanced stages of BC.

Background: Bladder cancer (BC) remains a health concern with high recurrence rates, prompting novel approaches to risk assessment and monitoring. Beyond established clinicopathological markers, growing attention focuses on psychophysiological factors, including stress perception and autonomic nervous system (ANS) regulation. Heart rate variability (HRV), a non-invasive measure of ANS balance, may provide insights into physiological alterations in BC. Given individual variability in stress responses, this study examined whether HRV parameters and their associations with perceived stress differ between first-diagnosed patients, those with recurrent disease, and healthy controls. Methods: The study included 30 first-diagnosed, 43 recurrent patients and 88 controls. Five-minute ECG recordings for HRV analysis were obtained using the Bittium Faros 180 device. Perceived stress was assessed with the Perceived Stress Scale (PSS). Results: SNS and Stress indices were higher in first-diagnosed patients compared to recurrent patients and controls. Differences in mean HR, DFA-α2, and the PNS index were significant only between first-diagnosed patients and controls. Overall, BC patients showed lower vagally-related HRV parameters (SDNN, RMSSD, DCmod, SD1, PNS index), overall autonomic activity (TINN, total power), and higher sympathetically-related parameters (mean HR, ACmod, SNS, Stress index) than controls. Higher PSS correlated with increased sympathetic and decreased parasympathetic HRV, particularly in first-diagnosed patients. Conclusion: Slovak BC patients demonstrated autonomic imbalance, with sympathetic dominance more pronounced in newly-diagnosed than recurrent patients; both groups showed greater imbalance than controls. HRV parameters also correlated more strongly with perceived stress in first-diagnosed patients. These findings support the value of psychophysiological and HRV monitoring in early BC care.

Chronic inflammation contributes to bladder cancer (BC) development and progression through dysregulated cytokine signaling and tumor–immune interactions. This case–control study investigated associations between IL6 rs1800795, TNF rs1800629, CCL2 rs1024611, and VEGFA rs699947 polymorphisms, circulating cytokine levels, clinicopathological characteristics, and autonomic nervous system balance assessed by heart rate variability (HRV) in 73 BC patients and 88 controls. Genotyping was performed using PCR–RFLP, serum cytokine levels were measured by ELISA, and associations were evaluated using logistic, linear regression, and survival analyses. No significant associations with BC risk were observed for IL6, TNF, or VEGFA variants. However, the CCL2 rs1024611 GG genotype was associated with increased BC risk (recessive model: OR = 5.82, p = 0.026). Stratified analyses showed a lower frequency of the IL6 rs1800795 C allele and TNF rs1800629 GA genotype in high-grade and muscle-invasive tumors, suggesting potential associations with reduced tumor aggressiveness. No polymorphism was associated with serum cytokine levels or disease-free survival. In BC patients, the TNF rs1800629 A allele was associated with higher parasympathetic-related HRV indices and lower sympathetic parameters, whereas no such associations were observed in controls. These findings indicate that genetic variation within inflammatory pathways may contribute to BC susceptibility and tumor phenotype and may also modulate neuroimmune interactions.