Markers Of Damage Research Articles

Renal tubular damage as an independent risk factor for all-cause and cardiovascular mortality in a community-based population: the Takahata study.

Renal tubular damage plays a crucial role in the development of end-stage kidney disease, a risk factor for cardiovascular events and mortality. However, the relationship between renal tubular damage and all-cause and cardiovascular mortality rates in the general population remains unclear. To address this gap, we conducted a cohort study in the general population using the urinary β2-microglobulin-creatinine ratio (UBCR) as a marker of renal tubular damage. This study included 3427 residents aged ≥ 40years in Takahata, Japan. We examined the association between the UBCR values in single-spot urine samples at enrollment and all-cause and cardiovascular mortality rates within a median follow-up of 9.2years. The participants were divided into two groups based on their UBCR levels (< 300μg/g and ≥ 300μg/g groups). Kaplan-Meier analysis showed a significantly higher incidence of all-cause and cardiovascular mortality rates in the high UBCR group (log-rank P < 0.01). Multivariable Cox proportional hazards model adjusted for age, sex, estimated glomerular filtration rate (eGFR), urine albumin level, smoking, and comorbidities showed a significantly higher hazard ratio of 1.49 (95% confidence interval (CI) 1.10-2.03, P = 0.01) for all-cause mortality and a hazard ratio of 1.73 (95% CI 1.00-2.98, P = 0.048) for cardiovascular mortality in the high-UBCR group. The net reclassification index was significantly improved by adding a high UBCR to the conventional risk factors. UBCR is an independent risk factor for all-cause and cardiovascular mortality in the general population, independent of eGFR and urinary albumin levels.

Antioxidant supplementation boosts the advantages of CrossFit workouts on oxidative and muscle damage markers in obese males.

Supplementing with antioxidants may be one of the most efficient means of minimizing oxidative stress during workouts in obese individuals. The aim of this study is to identify the results after twelve weeks of CrossFit workouts combined with Spinach thylakoid extract on the levels of insulin resistance (insulin and Homeostatic Model Assessment of Insulin Resistance [HOMA-IR]), fasting blood sugar (FBS), malondialdehyde (MDA), creatine kinase (CK), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), and superoxide dismutase (SOD), glutathione peroxidase (GPx) in obese males. Sixty-eight males with an average age of 27 ± 8 yrs and a BMI of 32.6 ± 2.6kg.m- 2 were randomly split into four groups each consisting of seventeen individuals. : control group (CG), supplement group (SG), training group (TG), and training + supplement group (TSG). After initial assessments, the two training groups (TG and TSG) started on a 12 weeks of the CrossFit workouts program involving three sessions per week each lasting up to 60min. Participants in supplement groups ingested 30min before lunch, 5 gof Spinach thylakoid extract per day or one sachet of raw corn starch in the control group. Baseline and post-intervention measurements were performed 48h pre- and post-last session, respectively. The findings revealed noteworthy relationships between the exercise groups and timefor TAC, SOD, GPx, MDA, CK, and LDH (p < 0.001, ES: 0.88, 0.88, 0.8, 0.4, 0.7, and 0.7, respectively). In addition, there were statistically significant differences among study groups after attending the intervention program in TAC (ES: 0.88), SOD (ES: 0.92), GPX (ES: 0.85), MDA (ES: 0.5), CK (ES: 0.7) and LDH (ES: 0.8). The effect sizes of insulin (0.77), glucose (0.21), and HOMA-IR (0.44) varied significantly (p < 0.05) among the groups. The results demonstrated that CrossFit workouts for 12 weeks combined with Spinach thylakoid extract in men with obesity may prevent oxidative damage caused by obesity and CrossFit workouts.

Mechanistic Insights Into Redox Damage of the Podocyte in Hypertension.

Podocytes are specialized cells within the glomerular filtration barrier, which are crucial for maintaining glomerular structural integrity and convective ultrafiltration. Podocytes exhibit a unique arborized morphology with foot processes interfacing by slit diaphragms, ladder-like, multimolecular sieves, which provide size and charge selectivity for ultrafiltration and transmembrane signaling. Podocyte dysfunction, resulting from oxidative stress, dysregulated prosurvival signaling, or structural damage, can drive the development of proteinuria and glomerulosclerosis in hypertensive nephropathy. Functionally, podocyte injury leads to actin cytoskeleton rearrangement, foot process effacement, dysregulated slit diaphragm protein expression, and impaired ultrafiltration. Notably, the renin-angiotensin system plays a pivotal role in podocyte function, with beneficial AT2R (angiotensin receptor 2)-mediated nitric oxide (NO) signaling to counteract AT1R (angiotensin receptor 1)-driven calcium (Ca2+) influx and oxidative stress. Disruption of this balance contributes significantly to podocyte dysfunction and drives albuminuria, a marker of kidney damage and overall disease progression. Oxidative stress can also lead to sustained ion channel-mediated Ca2+ influx and precipitate cytoskeletal disorganization. The complex interplay between GPCR signaling, ion channel activation, and redox injury pathways underscores the need for additional research aimed at identifying targeted therapies to protect podocytes and preserve glomerular function. Earlier detection of albuminuria and podocyte injury through routine noninvasive diagnostics will also be critical in populations at the highest risk for the development of hypertensive kidney disease. In this review, we highlight the established mechanisms of oxidative stress-mediated podocyte damage in proteinuric kidney diseases, with an emphasis on a hypertensive renal injury. We will also consider emerging therapies that have the potential to selectively protect podocytes from redox-related injury.

Point‐of‐care testing of DNA damage markers‐8‐hydroxy‐2′‐deoxyguanosine based on cobalt‐iron‐platinum‐ruthenium/N doped ordered mesoporous carbon

AbstractIn this work, we achieved point of care detection of DNA damage marker 8‐hydroxy‐2’‐deoxyguanosine (8‐OH‐dG) on tetrapartite metal nanoparticles loaded ordered mesoporous carbon composite nanomaterials (Co‐Fex‐Pt−Pd@NOMC). Nitrogen doping and co‐metal loading were achieved using dopamine as nitrogen, carbon sources and metal linker. In addition, the presence of catechol groups in dopamine with strong affinity for metal ions, make the simultaneous confinement of metals inside and outside the pores of ordered mesoporous carbon. Then, Fe, Pt and Pd metal nanoparticles were introduced to interact with Co nanoparticles to form four‐in‐one alloy nanoparticles by oil bath and carbonisation. The finally formed Co−Fe6‐Pt−Pd@NOMC nanocomposites exhibited excellent catalytic performance for the determination of 8‐OH‐dG. A lower limit of detection (LOD) of 0.044 μM, a wide linear range (0.175 μM–118.375 μM) and strong stability, reproducibility and selectivity were obtained. In addition, Co−Fe6‐Pt−Pd@NOMC realised the detection of 8‐OH‐dG in real human urine sample. At the same time, 8‐OH‐dG after DNA damage and guanine damage were also studied in this work. The electrochemical response of 8‐OH‐dG was combined with DNA damage to verify the mechanism of DNA damage. New solutions and idea were provided for the preparation of inorganic nanocomposites for the detection of 8‐OH‐dG in this work.

A real-life clinical application of cardiac magnetic resonance imaging in patients with acute myocarditis - one-center observational retrospective study.

The diagnosis of acute myocarditis is complex, with cardiac magnetic resonance (CMR) being a recommended diagnostic method. This study aimed to evaluate the real-life use of CMR in the diagnosis of acute myocarditis and to correlate CMR results with the degree of myocardial damage. This is a retrospective, observational tertiary single-center study of 90 consecutive patients (F/M:18/72, mean age:39 ± 14 years) hospitalized between 2015-2022 with a clinical diagnosis of acute myocarditis. The study population was divided into two groups: patients who underwent CMR+ and those who did not undergo CMR - In the CMR+ group, various sequences, including T1/T2-weighted imaging, late gadolinium enhancement (LGE), and mapping techniques, were used to assess myocardial inflammation and damage. CMR was performed in 39 patients (43.3%, F/M:10/29, mean age:41 ± 16 years). In this group, myocardial edema (increased T2 signal intensity) was detected in 29 patients, and LGE (signal intensity 2 standard deviations cabove normal on T1 images) was found in 39 patients. Diagnosis based on Lake Louise Criteria was possible in 29 cases. Edema negatively correlated with TnT levels (r = -0.412, p < 0.05) and positively with the number of LGE segments (r = 0.372, p < 0.05). Significant correlations were found between LVEF and LGE mass (r = -0.360, p < 0.05), and maximal TnT levels (r = -0.38, p < 0.05). CMR+ patients had lower myocardial damage markers and CRP concentrations compared to CMR- patients. CMR is underused in diagnosing acute myocarditis. Myocardial damage markers correlate with CMR-detected edema and volumetric measures, but not LGE extent. More research is needed to enhance risk assessment and treatment.

Abstract 4139191: ETX-258 - A GalOmic™ siRNA for the Treatment of Heart Failure Following Myocardial Infarction

Introduction: Heart failure with reduced ejection fraction (HFrEF) remains a significant clinical challenge, evidenced by high hospitalization rates and five-year mortality. Current treatments are limited by side effects, poor patient compliance, and the necessity for gradual drug titration. These challenges highlight the need for new therapies that are both safe and effective in targeting the structural remodeling pivotal to disease progression post-myocardial infarction (MI). e-therapeutics (ETX) uniquely combines computation and RNAi to discover life-transforming medicines. ETX’s RNAi platform, GalOmic™, enables generation of specific, potent, and long-acting siRNA therapies that effectively silence novel gene targets in hepatocytes. This highly specific mechanism of action limits unwanted side effects, positioning it as a promising approach to HFrEF treatment. Methods: Potent siRNAs against a hepatic target with cardioprotective potential were designed in silico. Candidate siRNAs were screened in vitro in HEK293 cells and in vivo in C57BL/6J mice to select the lead GalOmic™ siRNA, ETX-258. MI was induced by ligation of the left anterior descending artery in C57BL/6J mice after which ETX-258 was injected subcutaneously weekly for 6 weeks. Eplerenone, a mineralocorticoid receptor antagonist which is part of the current treatment regimen for HFrEF, was used as a comparator. Cardiac function was assessed by echocardiography at 2-, 4- and 6-weeks post-MI. Cardiac damage and structural remodeling were evaluated using circulating biomarkers of cardiac function and histological assessment. Results: ETX-258 was selected as a highly active siRNA for the treatment of heart failure with a long duration of action. Post-MI treatment with ETX-258 significantly improved key echocardiographic parameters of cardiac function, including ejection fraction and total cardiac output, achieving results comparable to eplerenone. Additionally, both structural cardiac parameters and markers of damage and remodeling showed significant improvements, reaching similar levels in both ETX-258 and eplerenone-treated mice. Conclusions: High unmet need remains for HFrEF patients despite existing therapies. These results highlight the potential of ETX-258 to improve cardiac function and pathogenic structural remodeling post-MI. This, paired with the long duration of action and favorable safety profile of GalOmic™ siRNAs, makes ETX-258 a promising candidate for further clinical development.

Functional and vascular neuroimaging in maritime pilots with long-term sleep disruption.

The mechanism underlying the possible causal association between long-term sleep disruption and Alzheimer's disease remains unclear Musiek et al. 2015. A hypothesised pathway through increased brain amyloid load was not confirmed in previous work in our cohort of maritime pilots with long-term work-related sleep disruption Thomas et al. Alzheimer's Res Ther 2020;12:101. Here, using functional MRI, T2-FLAIR, and arterial spin labeling MRI scans, we explored alternative neuroimaging biomarkers related to both sleep disruption and AD: resting-state network co-activation and between-network connectivity of the default mode network (DMN), salience network (SAL) and frontoparietal network (FPN), vascular damage and cerebral blood flow (CBF). We acquired data of 16 maritime pilots (56 ± 2.3years old) with work-related long-term sleep disruption (23 ± 4.8 working years) and 16 healthy controls (59 ± 3.3years old), with normal sleep patterns (Pittsburgh Sleep Quality Index ≤ 5). Maritime pilots did not show altered co-activation in either the DMN, FPN, or SAL and no differences in between-network connectivity. We did not detect increased markers of vascular damage in maritime pilots, and additionally, maritime pilots did not show altered CBF-patterns compared to healthy controls. In summary, maritime pilots with long-term sleep disruption did not show neuroimaging markers indicative of preclinical AD compared to healthy controls. These findings do not resemble those of short-term sleep deprivation studies. This could be due to resiliency to sleep disruption or selection bias, as participants have already been exposed to and were able to deal with sleep disruption for multiple years, or to compensatory mechanisms Mentink et al. PLoS ONE. 2021;15(12):e0237622. This suggests the relationship between sleep disruption and AD is not as strong as previously implied in studies on short-term sleep deprivation, which would be beneficial for all shift workers suffering from work-related sleep disruptions.

Prognostic nutritional index and albuminuria in adults aged 20 years and above: a cross-sectional analysis in the United States

Background and objectiveAlbuminuria is an important early marker of kidney damage and progression of chronic kidney disease and is also linked to several chronic systemic diseases. The Prognostic Nutritional Index (PNI) is widely used in the assessment of multiple diseases. However, research dealing with the relationship between PNI and albuminuria remains scarce. This research project aims to examine this association.Methods and materialsThe present study employed data from the National Health and Nutrition Examination Survey (NHANES) between 2017 and 2020, including 7,737 adult participants who met the study criteria. PNI was analyzed as a quartile-categorized variable. Multivariable regression models and smoothing curve fitting were adopted to examine the relationship between PNI and albuminuria. In order to ascertain the stability of the association across different populations, subgroup analyses were performed.ResultsThe study found a statistically significant inverse relationship between higher PNI levels and the prevalence of albuminuria. The fully adjusted model indicates that a one-unit increase in PNI is associated with a 4% reduced odds of albuminuria prevalence [0.96 (0.93, 0.98)]. Quartile analysis showed a stable inverse relationship, with the highest PNI quartile having the significantly lower odds of albuminuria prevalence [0.76 (0.62, 0.94), p for trend = 0.0004]. Smooth curve fitting and two-piecewise linear regression models indicated a nonlinear relationship between PNI and albuminuria, with a turning point at 42. Subgroup analysis confirmed the reliability of the inverse relationship between PNI and albuminuria across all groups.ConclusionThe findings of this study indicated that higher PNI levels are significantly inversely related to the odds prevalence of albuminuria. PNI could serve as an important predictor for the occurrence of albuminuria. Further prospective studies are needed to validate this association.

Abstract 4137913: Role of serial evaluation of myocardial inflammatory activity and oxidative stress in determining the therapeutic efficacy of immunosuppression and clinical outcome in patients with cardiac sarcoidosis

Background: Cardiac sarcoidosis (CS) was characterized by formation of granulomas in the heart. Enhancement in myocardial inflammatory activity and oxidative stress is a crucial cause of major cardiovascular adverse events (MACE). Although immunosuppressive therapy is recommended for active CS, there is no established markers for treatment and prognosis. Hypothesis: We hypothesized that the inflammation and oxidative stress in heart were associated with MACE after steroid therapy. Aims: We identified prognostic markers for MACE in patients with CS after steroid therapy. Methods: This study was a prospective observational cohort study. Patients with CS diagnosed according to Japanese criteria were enrolled in this study. Patients with abnormal accumulation of 18 F-FDG in heart were treated with steroids with standard guideline-recommended protocol. 18 F-FDG PET were performed after more than 6 months of induction. Urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage, and indices of cardiac and renal function were measured. The major outcome was a composite of the first sustained ventricular tachycardia (sVT) /sudden cardiac death (SCD), hospitalization for heart failure, and radiological relapse with exacerbation of clinical manifestation. Results: Fifty consecutive patients with CS underwent steroid therapy and followed up (median follow-up period of 58 months). 39 of 50 patients underwent 18F-FDG PET/CT more than 6 months after steroid therapy. During the follow-up period, 17 of 39 patients showed MACE, consisting of sVT/SCD (N= 11), hospitalization (N= 2) and radiological relapse (N= 4). A Cox proportional-hazard model showed that the U-8-OHdG and SUV max value of FDG-PET were independent predictors of MACE. ROC analysis revealed that the cut-off values of U-8-OHdG and SUV max for predicting the MACE were 11.6 ng/mg Cr (AUC 0.913, sensitivity 86.7%, specificity 90.0%) and 4.64 (AUC 0.878, sensitivity 76.5%, specificity 91.0%), respectively (Fig.1). Patients with a U-8-OHdG ≧11.6 ng/mg Cr or SUV max ≧4.64 had a significantly higher MACE risk (P values for U-8-OHdG and SUV max were both 0.001 by Log Rank analysis) (Fig.2). It is noted that U-8-OHdG &lt;11.6 ng/mg Cr and SUV max &lt;4.64 after steroid therapy indicate the good responses to the immunosuppressive therapy and better prognosis (Fig.3). Conclusion: U-8-OHdG and SUV max may be useful markers in determining the therapeutic efficacy and clinical outcome in patients with CS.

Bactericidal effect of far ultraviolet-C irradiation at 222 nm against bacterial peritonitis.

Far ultraviolet-C irradiation at 222 nm has potent bactericidal effects against severe infections such as peritonitis, with minimal cytotoxicity. Bacterial peritonitis due to bowel perforation is a serious condition with high mortality despite current treatments. This study investigated the safety and efficacy of intraperitoneal far ultraviolet-C irradiation at 222 nm. In vitro experiments optimized the fluid conditions for bacterial or protein concentrations prior to in vivo evaluation. In vivo efficacy was assessed in a rat peritonitis model induced by Escherichia coli, measuring intra-abdominal bacterial concentration, blood cytokine levels, and mortality rates. Safety was evaluated by analyzing cyclobutane pyrimidine dimers as markers of DNA damage in five abdominal organs: stomach, small intestine, colon, liver, and spleen. Statistical analyses employed parametric methods for normally distributed data and non-parametric methods for data without normality. Optimal in vitro conditions included 106 CFU/mL bacteria, 0.5 mW/cm2 irradiation, and 10-3 mg/mL protein. In the rat model, far ultraviolet-C irradiation at 222 nm significantly decreased intra-abdominal bacteria, reduced blood cytokines (interleukin-1β and interleukin-6), and elevated survival rates from 20% to 60%, compared to lavage alone. The formation of cyclobutane pyrimidine dimers was significantly lower with 222 nm irradiation than with 254 nm, suggesting reduced DNA damage. These findings indicate that far ultraviolet-C irradiation at 222 nm, when combined with lavage, represents a promising therapeutic strategy for bacterial peritonitis, providing effective bacterial reduction and a favorable safety profile. Further research is needed to verify these findings and investigate long-term safety and potential clinical applications.

Abstract 4134777: Predictive Factors for Early Recovery from Mechanical Circulatory Support in Patients with Fulminant Myocarditis

Background: Fulminant myocarditis (FM) requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is fatal and has a complicated clinical course. In such FM cases, predicting which cases are likely to achieve early recovery is crucial for developing acute-phase treatment strategies. We aimed to examine the factors predicting early recovery in fatal cases of FM requiring VA-ECMO using multicenter cohort of patients with myocarditis. Methods: We retrospectively analysed 343 patients with FM requiring VA-ECMO between April 2012 and March 2017. The early recovery group was defined as patients who were successfully weaned off mechanical circulatory support (MCS) within 7 days from MCS deployment and discharged with favorable outcomes. We divided patients into early recovery group and non-early recovery group. Predictors of early recovery were investigated by performing a multivariate analysis, including significant variables ( p &lt;0.05) identified from a univariate analysis of baseline clinical parameters and meaningful variables from previous reports. Results: Among the eligible patients, 71 were assigned to the early recovery group, whereas 272 were assigned to the non-early recovery group. The baseline patient demographics showed the early recovery group was significantly younger (45 [30-63] years vs. 56.5 [40-67] years, p =0.003), had higher WBC counts (11,400 [8,500-16,000] /μL vs. 9,900 [7,162.5-13,297.5] /μL, p =0.009), and had lower CK-MB levels (38.5 [18.0-75.3] U/L vs. 73.0 [42.5-137.0] U/L, p &lt;0.001), than the non-early recovery group. In the histological diagnosis, the proportions of lymphocytic and eosinophilic myocarditis were similar between the two groups, whereas the proportions of giant cell myocarditis tended to be higher in the non-early recovery group. Multivariate analysis showed the independent predictors of early recovery were age ≤40 years (OR: 3.25; 95% CI: 1.42-7.44), WBC ≥ 11,000 /μL (OR: 3.10; 95% CI: 1.39-6.86) and CK-MB ≤ 61 U/L (OR: 2.46; 95% CI: 1.06-5.72), and if all conditions were fulfilled, the early recovery rate increased to 61.5%. Conclusions: Early recovery group had higher inflammatory parameter levels but lower myocardial damage marker levels on admission in addition to age ≤40 years, suggesting that patients having a strong acute-phase inflammatory response with a lower degree of myocardial damage, could recover earlier.

Scalp condition improvement with botanical extracts possessing chemical and physical antioxidant activity.

Oxidative stress is implicated in scalp and hair health manifesting in several ways, including skin barrier, hair retention, healthy hair appearance and scalp sensation. We previously linked markers of oxidative damage to dandruff and skin barrier impairment and have linked key anti-dandruff technologies to the resolution of these issues. Here we expand the therapeutic space demonstrating many botanical extracts offer protective benefits against ROS stress via both chemical and biological antioxidant mechanisms. Chemical antioxidant activity of 10 botanical extracts was measured using oxygen radical absorbance capacity (ORAC) and biological antioxidant activity was measured using a Nrf-2 cell assay. A three-dimensional human keratinocyte skin equivalent model from MatTek was used to measure efficacy of reducing reactive oxygen species (ROS) from both the botanicals added as a solution and from a shampoo product. A 4-week consumer study with 56 panels was conducted with a leave-on treatment containing a botanical extract. Measurement of the oxidized lipids (9 and 13-Hydroxy-10E 12Z-octadecadienoic acid, HODE) extracted from scalp tape strips was made using gradient reversed-phase high-performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS). We demonstrated invitro that many botanical extracts exert antioxidant activity by quenching radicals in ORAC testing as well as activating biological antioxidant pathways via nrf-2 up-regulation in a cellular reporter system. Furthermore, we demonstrate these antioxidant activities for these botanicals in 3D skin models and ultimately show the reduction of lipid oxidation products in a consumer use context with a rosemary extract. Improved scalp condition can be achieved with incorporation of botanicals having the potential to exert antioxidant activity in hair/scalp care products.

NCOG-27. HIGHER LEVELS OF SERUM ICAM-1 AND IL-10 ARE ASSOCIATED WITH COGNITIVE DYSFUNCTION IN BOTH IDH-WILDTYPE AND IDH-MUTANT GLIOMA

Abstract BACKGROUND Cognitive dysfunction is common among glioma patients, but the contribution of specific mechanisms to the development of cognitive symptoms is unclear. Circulating levels of proteins linked to neurodegeneration, inflammation, and vascular damage have been associated with cognitive symptoms in neurological diseases and aging, but their prognostic value in glioma is unknown. Here, we examined associations between cognitive symptoms and serum levels of protein biomarkers in glioma patients. METHODS Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA, scores ≤ 25 = cognitive dysfunction). Cytokines (interleukin-1β [IL-1β], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ [IFN-γ], tumor necrosis factor-α [TNF-α]), and neurodegeneration (neurofilament light chain [NfL], tau, glial fibrillary acidic protein [GFAP]), and vascular damage markers (Serum amyloid A [SAA], C-reactive protein [CRP], vascular cell adhesion molecule 1 [VCAM-1], and intercellular adhesion molecule 1 [ICAM-1]) were measured using ultrasensitive assays (Meso Scale Discovery). RESULTS Patients (n=73) were predominantly male (58%), white (74%), with a median age of 44 (range=24,74). Cognitive dysfunction was found in 53% of the patients. Levels of NfL (p=0.035), IL-6 (p=0.006), IL-10 (p=0.007), TNF-α (p=0.035), IFN-γ (p=0.011), CRP (p=0.016), VCAM-1 (p=0.012), and ICAM-1 (p&amp;lt;0.001) were higher in patients with cognitive dysfunction when compared to those with normal cognition. After adjusting for isocitrate dehydrogenase (IDH) tumor mutation status, age, tumor grade, and number of surgeries, higher levels of ICAM-1 and IL-10, but not other markers, remained associated with cognitive dysfunction. MoCA scores were negatively correlated with GFAP (r=-0.24, p=0.038), IFN-γ (r=-0.31, p=0.008), IL-6 (r=-0.29, p=0.014), IL-10 (r=-0.24, p=0.039), and ICAM-1 (r=-0.39, p&amp;lt;0.001). CONCLUSIONS ICAM-1 and IL-10 levels were higher in patients with MOCA determined cognitive dysfunction, suggesting an association between cognitive symptoms and inflammation and vascular impairment in glioma patients. Future analyses in larger longitudinal cohorts are warranted to assess the predictive value of protein biomarkers.

Evaluation of the cell death markers for aberrated cell free DNA release in high altitude pulmonary edema.

The effect of high altitude (HA, altitude >2500 m) can trigger a maladaptive response in unacclimatized individuals, leading to various HA illnesses such as high altitude pulmonary edema (HAPE). The present study investigates circulating cell free (cf) DNA, a minimally invasive biomarker that can elicit a pro-inflammatory response. Our earlier study observed altered cfDNA fragment patterns in HAPE patients and the significant correlation of these patterns with peripheral oxygen saturation levels. However, the unclear release mechanisms of cfDNA in circulation limit its characterization and clinical utility. The present study not only observed a significant increase in cfDNA levels in HAPE patients (27.03 ± 1.37 ng/ml; n = 145) compared to healthy HA sojourners (controls, 14.57 ± 0.74 ng/ml; n = 65) and highlanders (HLs, 15.50 ± 0.8 ng/ml; n = 34) but also assayed the known cell death markers involved in cfDNA release at HA. The study found significantly elevated levels of the apoptotic marker, annexin A5, and secondary necrosis or late apoptotic marker, High mobility group box 1, in HAPE patients. In addition, we observed ahigher oxidative DNA damage marker, 8-hydroxy-2'-deoxyguanosine, in HAPE compared to controls, suggestive of the role of oxidative DNA status in promoting the inflammatory potential of cfDNA fragments and their plausible role in manifesting HAPE pathophysiology. Extensive in vitro future assays can confirm theimmunogenic role of cfDNA fragments that may act as a danger-associated molecular pattern and associate with markers of cellular stresses in HAPE.

Ameliorative effect of rutecarpine supplementation against cisplatin-induced nephrotoxicity in rats via inhibition of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, high-mobility group box 1, and nuclear factor kappa B.

Cisplatin, the pioneering heavy metal compound, stands out as a potent drug for the treatment of various solid tumors. However, its clinical utility is hampered by notable toxicity and adverse effects, particularly nephrotoxicity. The potency of rutecarpine, a phytochemical, in mitigating cisplatin-induced nephrotoxicity was assessed in the present study. In this experimental setup, healthy male Wistar rats were grouped into four and Group I rats served as the control group, receiving only vehicle control. Group II rats were subjected to cisplatin treatment alone, administered intraperitoneally at a dosage of 7mg/kg body weight on the 19th, 20th, and 21st days. Group III and IV rats were orally administered with rutecarpine at doses of 10 and 20mg/kg body weight, respectively, starting from Day 1 and continuing daily for 21 days. Additionally, they were injected intraperitoneally with cisplatin at the same dosage and schedule as Group II. Relative kidney weight and renal biochemical markers blood urea nitrogen, lactate dehydrogenase, serum urea, and creatinine were measured to assess rutecarpine inhibitory potency against cisplatin toxicity. Markers of oxidative damage and antioxidants levels were quantified in the ruteacarpine- and cisplatin-treated rats. The study investigated the anti-inflammatory property of rutecarpine in cisplatin-induced nephrotoxicity by analyzing inflammatory cytokines. Renal tissue levels of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, high-mobility group box 1, and nuclear factor kappa B, key markers of nephrotoxicity, were quantified to assess rutecarpine's potential to mitigate cisplatin-triggered damage. Histopathological examinations were performed to confirm the impact of rutecarpine against cisplatin-induced nephrotoxicity. Treatment with rutecarpine notably reduced renal biochemical markers, prevented renal edema, and attenuated oxidative stress-induced damage in cisplatin-treated rats. Both inflammatory and nephrotoxicity markers showed significant decreases in rats treated with rutecarpine along with cisplatin. Histological analysis affirmed that rutecarpine pretreatment effectively prevented cisplatin-induced nephrotoxicity. The study findings demonstrate that rutecarpine ameliorates cisplatin-triggered nephrotoxicity through its antioxidant and anti-inflammatory properties, suggesting that rutecarpine supplementation alongside cisplatin treatment could potentially reduce nephrotoxicity in cancer patients.

Proteinuria and Progression of Renal Damage: The Main Pathogenetic Mechanisms and Pharmacological Approach

The integrity of the glomerular filtration barrier maintains protein excretion below 150 mg/day. When urinary proteins increase, this indicates damage to the filtration barrier. However, proteinuria is not only a marker of kidney damage but also exacerbates it through various mechanisms involving the glomerular and tubulointerstitial compartments. Therefore, it is essential to intervene with renoprotective action that reduces the proteinuria. In this context, Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are cornerstone treatments. Recent advancements include sodium–glucose cotransporter 2 inhibitors, initially used for glycemic control, now recognized for their renoprotective properties in both diabetic and non-diabetic populations. Another drug, Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has emerged as a promising agent, offering anti-inflammatory and antifibrotic benefits with fewer side effects than traditional steroidal options. Finally, dual inhibition of angiotensin II and endothelin-1 receptors through agents like Sparsentan presents a novel approach with significant antiproteinuric effects in IgA nephropathy and focal segmental glomerulosclerosis. This brief review summarizes the mechanisms by which proteinuria promotes kidney damage and the renoprotective therapeutic approaches available, which can be combined with lifestyle modifications and specific treatments for underlying diseases to mitigate the progression of chronic kidney disease.

Lipid-core nanocapsules containing simvastatin do not affect the biochemical and hematological indicators of toxicity in rats.

Our research group previously studied the effectiveness of lipid-core nanocapsules (LNC) containing simvastatin (SV-LNC) in treating cognitive impairment in rats. While our results were promising, we needed to evaluate the potential toxicity of the nanoparticles themselves. This study aimed to compare the biochemical and hematological parameters of adult Wistar rats receiving LNC or SV-LNC to those receiving low doses of simvastatin crystals dispersed in a saline solution over 45days. We discovered that LNC and SV-LNC, which are both nanometers in size with low polydispersity index, negative zeta potential, and high SV encapsulation efficacy, were not more toxic than SV crystals based on various biochemical markers of hepatic, pancreatic, renal, mineral, bony, alkaline phosphatase, glucose, and uric acid damage. Furthermore, LNC exhibited no toxicity for hematological parameters, including red and white blood cell counts. Based on this animal model of toxicological study, our findings suggest that long-term administration of LNC is a safe and promising nanocarrier.

Multi-Omic characterization of the effects of Ocrelizumab in patients with relapsing-remitting multiple sclerosis

The study examined changes in the plasma proteome, metabolome, and lipidome of N = 14 patients with relapsing-remitting multiple sclerosis (RRMS) initiating treatment with ocrelizumab, assayed at baseline, 6 months, and 12 months. Analyses of >4000 circulating biomarkers identified depletion of B-cell associated proteins as the early effect observed following ocrelizumab (OCR) initiation, accompanied by the reduction in plasma abundance of cytokines and cytotoxic proteins, markers of neuronaxonal damage, and biologically active lipids including ceramides and lysophospholipids, at 6 months. B-cell depletion was accompanied by decreases in B-cell receptor and cytokine signaling but a pronounced increase in circulating plasma B-cell activating factor (BAFF). This was followed by an upregulation of a number of signaling and metabolic pathways at 12 months. Patients with higher baseline brain MRI lesion load demonstrated both higher levels of cytotoxic and structural proteins in plasma at baseline and more pronounced biomarker change trajectories over time. Digital cytometry identified a putative increase in myeloid cells and a pro-inflammatory subset of T-cells. Therapeutic effects of ocrelizumab extend beyond CD20-mediated B-cell lysis and implicate metabolic reprogramming, juxtaposing the early normalization of immune activation, cytokine signaling and metabolite and lipid turnover in periphery with changes in the dynamics of immune cell activation or composition. We identify BAFF increase following CD20 depletion as a tentative compensatory mechanism that contributes to the reconstitution of targeted B-cells, necessitating further research.

A healthy lifestyle is prospectively associated with lower onset of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an unhealthy lifestyle. However, there is limited prospective evidence regarding the association between combined lifestyle factors and MASLD. This study aims to test the association of a combination of lifestyle components, expressed as a healthy lifestyle index (HLI), and unhealthful eating behavior habits with MASLD, insulin resistance (IR), liver fibrosis, and metabolic dysfunction-associated steatohepatitis. A prospective cohort study was conducted among participants of metabolic and hepatic screening surveys. MASLD was evaluated by ultrasonography or controlled attenuation parameter at 2 time points to assess new-onset, persistence, or remission, and IR was estimated by homeostasis model assessment. Presumed liver fibrosis and metabolic dysfunction-associated steatohepatitis were evaluated using FibroMax biomarkers. The HLI was calculated as the sum of 4 lifestyle components: nonsmoking, healthy weight, healthy diet, and physical activity. The final cohort included 315 subjects with 6.7 years of follow-up, 40-70 years old. In multivariable analyses, a favorable lifestyle (≥3 components) was independently associated with lower odds of new-onset MASLD (OR = 0.42; 95% CI: 0.19-0.90). Similarly, a favorable lifestyle was associated with lower odds of new-onset/persistent (vs. never/remission) MASLD and IR, respectively (OR = 0.49; 95% CI: 0.30-0.80; OR = 0.40; 95% CI: 0.24-0.66). There was a dose-response association between HLI and new-onset/persistent MASLD and IR. A favorable lifestyle was associated with lower odds of new-onset metabolic dysfunction-associated steatohepatitis (OR = 0.50; 95% CI: 0.27-0.95). Adjusting for HLI, unhealthful eating behavior habits were associated with higher odds of MASLD prevalence (OR = 1.81; 95% CI: 1.07-3.06). Adherence to a healthy lifestyle is prospectively associated with lower odds of MASLD, markers of liver damage, and IR. A holistic approach that considers overall lifestyle and eating behavior may be useful for preventing MASLD.

Biological markers of bronchiolitis obliterans syndrome in recipients of allogeneic hematopoietic stem cell transplantation

Bronchiolitis obliterans syndrome (BOS) is a rare non-infectious pulmonary complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) or lung transplantation. Early diagnosis of BOS requires new approaches including the search for biological markers of pulmonary damage after allo-HSCT. The aim of this work is to review literary data on biological markers of BOS. Conclusion. Literary data on biomarkers of BOS in allo-HSCT recipients are limited. Further research is needed.