Inflammatory Biomarkers Research Articles

Gut dysbiosis mediates the association between antibiotic exposure and chronic disease

Antibiotics are safe, effective drugs and continue to save millions of lives and prevent long-term illness worldwide. A large body of epidemiological, interventional and experimental evidence shows that exposure to antibiotics has long-term negative effects on human health. We reviewed the literature data on the links between antibiotic exposure, gut dysbiosis, and chronic disease (notably with regard to the “developmental origins of health and disease” (“DOHaD”) approach). Molecular biology studies show that the systemic administration of antibiotic to infants has a rapid onset but also often a long-lasting impact on the microbial composition of the gut. Along with other environmental factors (e.g., an unhealthy “Western” diet and sedentary behavior), antibiotics induce gut dysbiosis, which can be defined as the disruption of a previously stable, functionally complete microbiota. Gut dysbiosis many harmful long-term effects on health. Associations between early-life exposure to antibiotics have been reported for chronic diseases, including inflammatory bowel disease, celiac disease, some cancers, metabolic diseases (obesity and type 2 diabetes), allergic diseases, autoimmune disorders, atherosclerosis, arthritis, and neurodevelopmental, neurodegenerative and other neurological diseases. In mechanistic terms, gut dysbiosis influences chronic disease through direct effects on mucosal immune and inflammatory pathways, plus a wide array of direct or indirect effects of short-chain fatty acids, the enteric nervous system, peristaltic motility, the production of hormones and neurotransmitters, and the loss of intestinal barrier integrity (notably with leakage of the pro-inflammatory endotoxin lipopolysaccharide into the circulation). To mitigate dysbiosis, the administration of probiotics in patients with chronic disease is often (but not always) associated with positive effects on clinical markers (e.g., disease scores) and biomarkers of inflammation and immune activation. Meta-analyses are complicated by differences in probiotic composition, dose level, and treatment duration, and large, randomized, controlled clinical trials are lacking in many disease areas. In view of the critical importance of deciding whether or not to prescribe antibiotics (especially to children), we suggest that the DOHaD concept can be logically extended to “gastrointestinal origins of health and disease” (“GOHaD”) or even “microbiotic origins of health and disease” (“MOHaD”).

Pre-transplant Screening for MMP-9 in Allogeneic HSCT Candidates

Purpose: InflammaDry® (Quidel Eye Health, San Diego, California), an FDA-approved point-of-care commercial test, measures matrix metalloproteinase-9 (MMP-9) levels in the tear film. MMP-9 is an inflammatory biomarker that is elevated in response to ocular surface stress, particularly observed in ocular graft-versus-host disease (oGVHD). The purpose of this study is to assess the prevalence of MMP-9 positivity and a score >4 on the OSDI-6 questionnaire in patients before allogeneic hematopoietic stem cell transplant (HSCT). Methods: A prospective, observational, cross-sectional single center pilot study was conducted among 23 patients (46 eyes) undergoing planned allogenic HSCT. InflammaDry® results, OSDI-6 questionnaire results, and development of oGVHD were collected. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and chi-square test were calculated. Results: InflammaDry® demonstrated high sensitivity (1.0) but low specificity (0.1429) for oGVHD development. The PPV was 0.25, while the NPV was 1.0. No statistical significance was found between InflammaDry® result and development of oGVHD (p-value> 0.05). Conclusion: InflammaDry® is not an effective tool for detecting the onset or predicting the risk of developing oGVHD. A significant percentage of patients exhibited ocular inflammation before allogeneic HSCT, suggesting that initiating prophylactic treatment could be valuable in reducing oGVHD development.

Biomarkers of Frailty in Patients with Advanced Chronic Liver Disease Undergoing a Multifactorial Intervention Consisting of Home Exercise, Branched-Chain Amino Acids, and Probiotics

Frailty in cirrhosis or advanced chronic liver disease (ACLD) is a relevant prognostic factor. In the present study, we aimed to analyze potential biomarkers associated with frailty and its improvement in patients with ACLD. We analyzed the serum of outpatients with ACLD who participated in a previous study (Román, Hepatol Commun 2024) in which frailty was assessed using the liver frailty index (LFI), and patients who were frail or prefrail were randomized to a multifactorial intervention (home exercise, branched-chain amino acids, and probiotics) or control for 12 months. We determined a biomarker battery of inflammation, bacterial translocation, and liver damage in blood and urine and blood metabolomics by 1H-NMR. Thirty-seven patients were included. According to the LFI, 32 patients were frail or prefrail, and 5 were robust. At baseline, LFI correlated with LBP, sCD163, mtDNA, FGF-21, urinary NGAL, urinary claudin-3, and the metabolites mannose, ethanol, and isoleucine. During the study, patients in the intervention group showed an improvement in LFI and a decrease in CRP, LBP, sCD163, and ccK18 compared to the control group. Metabolomics showed a decrease in dimethyl sulfone and creatinine and an increase in malonate, ornithine, isoleucine, and valine in the intervention group. We conclude that frailty in patients with ACLD is associated with biomarkers of systemic inflammation, bacterial translocation, and liver damage, and alterations of amino acid and short-chain fatty acid metabolism.

Type-2 Inflammation in Health and Disease: Prevalence, Risk Factors and Multimorbidity

Background: In patients with airflow obstruction, the levels of biomarkers of Type-2 (T2) inflammation serve to predict the effectiveness of inhaled corticosteroid and biological therapies. Elevated biomarkers of T2 inflammation, including fractional exhaled nitric oxide (FeNO, ≥20 ppb) and blood eosinophil counts (BEC, ≥300 cells/µL), were investigated in a population-based cohort of the Austrian LEAD study. Methods: A total of 4976 individuals (aged 18–82 years) were categorised into four groups based on their FeNO and BEC levels: normal with FeNO < 20 ppb and BEC < 300 cells/µL (n = 2634); FeNO ≥ 20 ppb only (n = 1623); BEC ≥ 300 cells/µL only (n = 340); and FeNO ≥ 20 ppb and BEC ≥ 300 cells/µL (n = 379). Results: In age- and sex-adjusted regression models, individuals with elevated BEC only were most associated with chronic cough and sputum production (odds ratios [95% CI]: 1.22 [0.78, 1.84] and 1.37 [1.13, 2.62], respectively), whilst individuals with both elevated T2 biomarkers were most associated with wheezing, dyspnoea and asthma (odds ratios [95% CI]: 2.27 [1.56, 3.26], 1.32 [0.64, 2.50] and 3.63 [2.69, 4.88] respectively). Elevated levels of both FeNO and BEC presented an additive effect in extrapulmonary conditions, particularly in allergy, eczema and rhino conjunctivitis (odds ratios [95% CI]: 2.30 [1.84, 2.88], 1.37 [1.03, 1.81] and 2.95 [2.34, 3.70], respectively). Conclusions: T2 inflammation marked by elevated levels of FeNO and/or BEC is not only associated with respiratory conditions but also extends to extrapulmonary characteristics, with an additive effect.

Association between Lactate dehydrogenase and 28-day all-cause mortality in patients with non-traumatic Intracerebral hemorrhage: A retrospective analysis of the MIMIC-IV database

Lactate dehydrogenase (LDH), a nonspecific inflammatory biomarker, has been used in the assessment of acute myocardial infarction, acute hepatitis, acute lung injury, and other severe diseases. However, no studies have evaluated the prognostic value of LDH in patients with non-traumatic intracerebral hemorrhage (ICH). This cohort study aims to assess the association between LDH levels and 28-day all-cause mortality in patients with non-traumatic ICH. Data for this retrospective cohort analysis were obtained from the MIMIC-IV (v2.2) database, and the study included patients with non-traumatic ICH as defined by the International Classification of Diseases, 9th and 10th editions. Patients were categorized into four distinct groups based on their LDH levels. The primary outcome of interest was the 28-day mortality rate. To analyze these associations and assess the consistency of interactions, subgroup analyses, Cox regression analysis, Kaplan-Meier (KM) curves, and nonlinear analysis were conducted. A total of 406 patients with non-traumatic ICH were enrolled in the study and were divided into quartiles based on LDH levels. The KM curve indicated that the 28-day all-cause mortality rate of patients in the Q4 group (LDH > 287.25) was significantly higher than in the Q1 (LDH < 194.7) (P < 0.001) and Q2 (194.7 < LDH < 233.0) (P < 0.001) groups, though not significantly different from Q3 (P = 0.140). Multivariate Cox proportional hazards analysis revealed that patients in the highest LDH quartile had a significantly increased risk of mortality compared to those in the lowest quartile across three models: unadjusted [HR, 3.401; 95% CI, 1.719–6.731; P < 0.001], partially adjusted [HR, 2.422; 95% CI, 1.211–4.846; P = 0.012], and fully adjusted [HR, 3.054; 95% CI, 1.522–6.126; P = 0.002]. Restricted cubic spline (RCS) models revealed an L-shaped association between LDH levels and the 28-day all-cause mortality rate, indicating a non-linear relationship (P < 0.001). No significant interactions were observed between LDH levels and other factors in the subgroup analyses (all P for interaction > 0.05). Our findings indicate a significant association between 28-day all-cause mortality and LDH levels in patients with non-traumatic intracerebral hemorrhage. Specifically, patients with elevated LDH levels within the first 24 hours of ICU admission are at a higher risk of mortality.

Noninvasive, Multimodal Inflammatory Biomarker Discovery for Systemic Inflammation (NOVA Study): Protocol for a Cross-Sectional Study.

Prolonged systemic inflammation is recognized as a major contributor to the development of various chronic inflammatory diseases. Daily measurements of inflammatory biomarkers can significantly improve disease monitoring of systemic inflammation, thus contributing to reducing the burden on patients and the health care system. There exists, however, no scalable, cost-efficient, and noninvasive biomarker for remote assessment of systemic inflammation. To this end, we propose a novel, multimodal, and noninvasive approach for measuring inflammatory biomarkers. This study aimed to evaluate the relationship between the levels of inflammatory biomarkers in serum (gold standard) and those measured noninvasively in urine, sweat, saliva, exhaled breath, stool, and core body temperature in patients with systemic inflammation. This study is a single-center, cross-sectional study and includes a total of 20 participants (10 patients with systemic inflammation and 10 control patients). Eligible participants provide serum, urine, sweat, saliva, exhaled breath, and stool samples for biomarker analyses. Core body temperature is measured using a sensor. The primary end point is the level of C-reactive protein (CRP). The secondary end points are interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α levels. The tertiary end points are fractional exhaled nitric oxide, calprotectin, and core body temperature. Samples will be collected in 2 batches, enabling preliminary analysis of the first batch (patients 1-5 from each group). The full analysis will include both batches. CRP and cytokine levels will be measured using enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay. For statistical analysis, the Shapiro-Wilk test will be used to evaluate the normality of the distribution in each variable. We will perform the 2-tailed t test or Wilcoxon rank sum test to compare the levels of inflammatory biomarkers between patients with systemic inflammations and control patients. Pearson and Spearman correlation coefficients will assess the relationship between inflammatory biomarkers from noninvasive methods and serum biomarkers. Using all-subset regression analysis, we will determine the combination of noninvasive methods yielding the highest predictive accuracy for serum CRP levels. Participants' preferences for sampling methods will be assessed through a questionnaire. The study received ethics approval from the independent research ethics committee of Canton Zurich on October 28, 2022. A total of 20 participants participated in the study measurements. Data collection started on February 22, 2023, and was completed on September 22, 2023. Participants were on average 52.8 (SD 14.4; range 24-82) years of age, and 70% (14/20) of them were women. The analysis results reporting findings are expected to be published in 2025. This study aims to evaluate the feasibility of noninvasive, multimodal assessment of inflammatory biomarkers in patients with systemic inflammation. Promising results could lead to the creation of noninvasive and potentially digital biomarkers for systemic inflammation, enabling continuous monitoring and early diagnosis of inflammatory activity in a remote setting. DERR1-10.2196/62877.

Biocompatible Naringin loaded low molecular peptide Nanogels are effective against human melanoma cells

Abstract Melanoma, a type of cancer, has the ability to metastasize and can be fatal. The lack of success in the treatment of melanoma with chemotherapeutic agents and the side effects have led to the search for new agents. Moreover, developing systems that will provide reduce side effects by using biocompatible carriers, may be beneficial. Naringin (NAR), from Citrus plants, has anticancer and anti-inflammatory properties. NAR is useful in formulations where it is used with a carrier due to its low water solubility and bioavailability with few toxicity. This study aimed to evaluate the effects of NAR-loaded peptide based Fmoc-FF nanogels on human melanoma (SK-MEL-30) cells. Characterization of NAR-loaded Fmoc-FF nanogels was carried out. The biocompatibility properties of Fmoc-FF and NAR-loaded nanogels were evaluated in mouse fibroblast (L929) cells, and their cytotoxic effects were evaluated in human melanoma (SK-MEL-30) cells by the MTT method. While the DCF-DA method was used to measure the effects on reactive oxygen species (ROS) release, the changes in oxidative stress biomarkers were examined by spectrophotometric analysis, tyrosinase enzyme activity and inflammation biomarkers were investigated by ELISA method. Comet method was used to evaluate antigenotoxic effects. It has been observed that loading NAR into Fmoc peptide gels may be effective in causing cytotoxic, genotoxic, anti-inflammatory and anti-tyrosinase effects and an increase in ROS release in melanoma cells. These results indicate that NAR-loaded Fmoc-FF gels, which have the feature of easy application to the skin, may be effective in the treatment of melanoma without causing toxic effects.

Maternal Dietary Improvement or Leptin Supplementation During Suckling Mitigates the Long-Term Impact of Maternal Obesogenic Conditions on Inflammatory and Oxidative Stress Biomarkers in the Offspring of Diet-Induced Obese Rats

This study investigates the impact of maternal nutrition during lactation on inflammation and oxidative stress in the offspring of diet-induced obese rats, along with the potential benefits of leptin supplementation during suckling. Dams were fed either a standard diet (SD), a western diet (WD) before and during gestation and lactation (WD-dams), or a WD switched to an SD during lactation (Rev-dams). Offspring were supplemented with leptin or vehicle during suckling and then fed an SD or WD until four months. Offspring of the Rev-dams exhibited improved metabolic indicators, including lower body weight, reduced plasma levels of TNF-alpha, a higher adiponectin/leptin (A/L) ratio, enhanced liver antioxidant defenses, and decreased inflammation markers in white adipose tissue (WAT) compared to WD-dams, with sex differences. Leptin supplementation further modulated these markers, reducing oxidative stress in liver and inflammation in WAT and liver (e.g., hepatic Tnfa expression decreased by 45% (males) and 41% (females) in the WD group on an SD), and improving the A/L ratio, with effects varying by maternal conditions and sex. In conclusion, this study underscores the importance of maternal nutrition and leptin intake during suckling in shaping long-term metabolic and inflammatory health in offspring, offering strategies to mitigate the adverse effects of maternal obesity on future generations.

The Effect of Black Chokeberry (Aronia melanocarpa) on Human Inflammation Biomarkers and Antioxidant Enzymes: A Systematic Review of Randomized Controlled Trials.

Consuming antioxidant-rich foods has been associated with potential benefits in managing chronic diseases by reducing oxidative stress and inflammation. This systematic review aimed to evaluate the effects of Aronia melanocarpa (aronia berry or chokeberry) on human inflammation biomarkers and antioxidant enzymes. A systematic search was conducted across multiple databases, including PubMed, Scopus, Science Direct, and Web of Science, to identify relevant studies investigating the potential effects of aronia on human inflammation biomarkers and antioxidant enzymes between April 2022 and November 2023. The selection of studies followed the PRISMA guidelines, data screening was conducted by 4 independent reviewers, and data extraction and risk-of-bias assessments were performed by 2 independent reviewers using the Cochrane Risk of Bias 2 tool. A total of 1986 studies were screened, and 18 studies that met the inclusion criteria were included in a systematic review that investigated the anti-inflammatory effects of aronia on various health parameters. These studies primarily focused on the effects of aronia on cardiometabolic diseases, performance in sport, and other health parameters. This study examined the effects of Aronia intervention on human health outcomes using aronia juice, extract, or oven-dried powder for a period of 4 to 13 weeks. The primary health parameters considered were C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1ß (IL-1ß), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione peroxidase (GSH-Px). The results showed that aronia had a beneficial effect on several inflammatory cytokines, including reductions in CRP, TNF-α and IL-6 concentrations, as well as elevated IL-10 levels. Moreover, positive changes have been observed in antioxidant enzyme systems, including; elevated SOD, GSH-Px and CAT activity. The findings of the presented studies provide evidence that Aronia melanocarpa may have beneficial effects on inflammatory markers. PROSPERO registration No. CRD42022325633.

Characterization of genetic landscape and novel inflammatory biomarkers in patients with adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is systemic autoinflammatory disorder of unknown aetiology. Genetic studies have been limited. Here, we conducted detailed genetic and inflammatory biomarker analysis of a large AOSD cohort to investigate the underlying pathology and identify novel targets for potential treatment. We investigated AOSD cases (n=60) for rare germline and somatic variants using whole exome sequencing with virtual gene panels. Transcriptome profiles were investigated by bulk RNA sequencing whole blood. Cytokine profiling was performed on an extended patient cohort (n=106), alongside measurements of NLRP3 inflammasome activation using a custom assay, and Type I Interferon (IFN) score using a novel method. We observed higher-than-expected frequencies of rare germline variants associated with monogenic autoinflammatory disorders in AOSD cases (AOSD 38.4% vs healthy controls 20.4%), and earlier onset of putative somatic variants associated with clonal haematopoiesis of indeterminate potential. Transcriptome profiling revealed positive correlation between Still's activity score (SAS) and gene expression associated with the innate immune system. ASC/NLRP3 specks levels and Type I IFN scores were significantly elevated in AOSD cases compared to healthy controls (p=0.0001 and 0.0015 respectively), in addition to several cytokines: IL-6 (p<0.0001), IL-10 (p<0.0075), IL-12p70 (p=0.0005), IL-18 (p<0.0001), IL-23 (p<0.0001), IFN-α2 (p=0.0009), and IFNγ (p=0.0002). Our study shows considerable genetic complexity within AOSD and demonstrates the potential utility of the ASC/NLRP3 specks assay for disease stratification and targeted treatment. The enriched genetic variants identified may not, by themselves, be sufficient to cause disease but may contribute to a polygenic model for AOSD.

Investigating Anti-Oxidative and Anti-Inflammatory Effects regarding Ethanol Extract of Allium Porrum L. in Rats with Type 2 Diabetes Mellitus

Background: Type 2 diabetes mellitus (T2D) is a common endocrine and metabolic disorder worldwide. Meanwhile, Allium Porrum L. (AP) has been recognized as one of the most eminent traditional herbal medicines with substantial health benefits. The aim of the present study is to evaluate anti-oxidative and anti-inflammatory effects of ethanol extract of AP in rats with T2D. Methods: 70 male Sprague-Dawley rats were randomly divided into 7 groups of 10 animals each. The study groups were as follows: The study groups were as follows: healthy control (HC); healthy control rats receiving 100 mg/kg of AP extract (HC.AP.100); diabetic control (DC); diabetic rats receiving 10 mg/kg metformin (DT.M.10); diabetic animals receiving 50 mg/kg of AP extract (DT.AP.50); diabetic rats receiving 100 mg/kg of AP extract (DT.AP.100); and diabetic animals receiving 200 mg/kg of AP extract (DT.AP.200). Results: After 6 weeks of intervention, the level of serum malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) were significantly increased (P=0.02) and (P=0.002), respectively; while superoxide dismutase (SOD) concentration was notably reduced (P=0.04) in DC.M.10 in comparison with that of the HC.AP.100 group. Also, compared to DC.M.10 group, all rats treated with metformin and AP showed a significant decrease in the level of MDA and TNF-α, along with an enhancement of SOD concentration (All P&lt;0.001). Moreover, in comparison with DT.M.10, DT.AP.50, and DT.AP.100 treatments, the DT.AP.200 group revealed a significantly higher improvement in serum TNF-α concentration (P=0.04, P=0.003 and P=0.003, respectively). Conclusion: The findings revealed that the use of AP extract for 6 weeks may have beneficial effects on oxidative stress and inflammatory biomarkers in T2D-induced rat models.

The Impact of Combined Cranberry Supplementation and Weight Loss Diet on Inflammatory, Antioxidant, and Apoptosis Biomarkers in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized, Double-Blinded, Controlled Clinical Trial

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease. The aim of this study is to evaluate the effect of combined weight loss diet and cranberry supplementation on anthropometric measurements, inflammation and antioxidant biomarkers in patients with NAFLD. Methods: In this randomized, double-blinded, and controlled clinical trial, 41 NAFLD patients were supplemented with either cranberry or placebo tablets for 12 weeks. Both groups followed a diet of 500-1000 calories less than the estimated energy requirements. Serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), cytokeratin 18 M30 (CK-18 M30), chemokine C-C motif ligand 2 (CCL2) and tumor necrosis factor alpha (TNF-α) were measured at both baseline and the end of the study. Results: Significant improvements in TAC were observed in the cranberry group and between the two groups (P=0.006 and P=0.011, respectively), but the changes in the placebo group were not significant (P=0.325). There were no statistically significant differences in the serum levels of MDA, CK-18 M30, CCL2 and TNF-α between the cranberry and the placebo groups (P&gt;0.05). Conclusions: It seems that daily consumption of cranberry supplement would be beneficial in increasing serum levels of TAC. Further studies are needed to investigate the effects of anti-inflammatory and antioxidant properties of cranberry on NAFLD.

Relationship between Diet-Related Inflammation and Hospitalization Risk and Disease Severity in Patients with COVID-19

Background: Increased serum concentrations of inflammatory biomarkers in patients indicate a strong association between COVID-19 and inflammation. However, the association between diet-related inflammation and COVID-19 has been less investigated. The aim of this study is to investigate whether the inflammatory scores of the diet are associated with the severity of COVID-19 disease and the probability of hospitalization of patients. Methods: The authors conducted a cross-sectional study involving 141 patients with COVID-19. The empirical dietary inflammatory pattern (EDIP) and dietary inflammation scores (DIS) were calculated based on a 147-item semi-quantitative food frequency questionnaire. The association between serum levels of inflammatory biomarkers and diet-related inflammation was also investigated. Results: 74 inpatients and 87 outpatients participated in this study. Higher DIS scores were significantly associated with an increased risk of COVID-related hospitalization (Tertile3 vs. tertile1: OR = 3·62; 95 % CI 1·43 to 9·14, P=0·008 after fully adjustment). This association with EDIP was also observed, but it was not significant. Conclusion: The data from this provide evidence that a pro-inflammatory diet was associated with higher risk of hospitalization due to high severity of COVID-19.

Evidence in Reaching Consensus in Usage of Mandibular Advancement Device for Pre- and Post-obstructive Sleep Apnea Treatment with Blood and Salivary Inflammatory Biomarkers Profiles

Evidence in Reaching Consensus in Usage of Mandibular Advancement Device for Pre- and Post-obstructive Sleep Apnea Treatment with Blood and Salivary Inflammatory Biomarkers Profiles

Neuroinflammatory Proteins in Huntington’s Disease: Insights into Mechanisms, Diagnosis, and Therapeutic Implications

Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by a CAG tract expansion in the huntingtin gene (HTT). HD is characterized by involuntary movements, cognitive decline, and behavioral changes. Pathologically, patients with HD show selective striatal neuronal vulnerability at the early disease stage, although the mutant protein is ubiquitously expressed. Activation of the immune system and glial cell-mediated neuroinflammatory responses are early pathological features and have been found in all neurodegenerative diseases (NDDs), including HD. However, the role of inflammation in HD, as well as its therapeutic significance, has been less extensively studied compared to other NDDs. This review highlights the significantly elevated levels of inflammatory proteins and cellular markers observed in various HD animal models and HD patient tissues, emphasizing the critical roles of microglia, astrocytes, and oligodendrocytes in mediating neuroinflammation in HD. Moreover, it expands on recent discoveries related to the peripheral immune system’s involvement in HD. Although current immunomodulatory treatments and inflammatory biomarkers for adjunctive diagnosis in HD are limited, targeting inflammation in combination with other therapies, along with comprehensive personalized treatment approaches, shows promising therapeutic potential.

Extra virgin olive oil beneficial effects on memory, synaptic function, and neuroinflammation in a mouse model of Down syndrome.

Clinical and preclinical studies have shown that extra virgin olive oil (EVOO), a major component of the Mediterranean diet, has beneficial effects on brain aging and cognition. Individuals with Down syndrome develop age-dependent cognitive decline and synaptic dysfunction. However, whether EVOO intake is beneficial in Down syndrome is not known. In this study, by implementing a mouse model of Down syndrome, we aimed to investigate the effect that chronic administration of EVOO has on memory, synaptic function, and neuroinflammation. Starting at 4 months of age Ts65dn mice were randomized to receive EVOO for 5 months in their diet, after which they were tested for learning and memory impairment. After euthanasia, synaptic function was measured in freshly obtained hippocampal slices, whereas brain tissues were assessed for inflammatory biomarkers. Compared with controls, mice receiving EVOO had a significant improvement in learning and spatial memory. Additionally, field potential recordings showed that treated mice had an improvement in synaptic function. Finally, array analysis showed that EVOO modulated the expression levels of several inflammatory biomarkers. Chronic administration of EVOO to a mouse model of Down syndrome has beneficial effects on memory impairments, synaptic function deficits and neuroinflammation. Our findings provide additional support for the potential therapeutic effects of EVOO also in individuals with Down syndrome.

The Effect of Exercise Program Interventions on Frailty, Clinical Outcomes, and Biomarkers in Older Adults: A Systematic Review

Background: Frailty is characterized by the decreased ability in older adults to handle daily or acute stressors due to age-related declines in physiological reserve and organ system performance. This condition results from the interaction of multiple physiological pathways and changes in biomarkers. Exercise programs are currently recommended to promote “healthy aging” in frail older adults. Objective: This systematic review aimed to evaluate the effectiveness of exercise program interventions in improving outcomes related to frailty, physical function, cognitive performance, and biomarkers in frail older adults. Methods: This study was designed according to the PRISMA guidelines. A systematic search was conducted in PubMed, Embase, and Scopus for studies published between 2014 and 2024. Two independent reviewers extracted data, with disagreements resolved by a third reviewer. Randomized controlled trials involving pre-frail or frail older adults aged 60 and above in all settings were included. The focus was on the impact of exercise programs, especially multicomponent interventions, on frailty outcomes and biomarkers. Results: Nine studies involving a total of 2083 participants met the inclusion criteria. The age range of participants was 65.35 ± 5.15 to 86.7 ± 4.00 years, with 64.7% being female. The results demonstrated that multicomponent exercise programs significantly improved frailty status, enhanced physical and cognitive function, and improved emotional well-being. Additionally, these programs led to significant reductions in inflammatory biomarkers, such as IL-6 and TNF-α, which are associated with frailty. Conclusion: This review highlights the beneficial effects of multicomponent exercise programs on pre-frail and frail older adults, providing evidence that these interventions improve physical and cognitive functions and emotional well-being, and reduce inflammation. These findings offer valuable insights into developing targeted interventions to manage frailty in clinical practice.

Assessing the evidence for health benefits of low-level weight loss: a systematic review.

Individuals with excess weight are at a higher risk for various physical and mental health conditions. Interventions targeting weight loss can improve health, with modest weight loss of five to ten percent of body weight often considered clinically meaningful for enhancing health outcomes. However, the benefits of achieving low-level weight loss ( < 5% body weight) are poorly understood. We aimed to systematically review relevant literature and synthesise the evidence that assessed the potential health benefits of losing less than five percent body weight. We searched seven academic databases and included studies in any language, from any country, with no time constraints. We included any intervention studies that assessed the impact of less than five percent weight loss on any measured physical or mental health markers or indices. 70 studies from 68 articles were included, with study participants ranging from 14 to 10,742. In total, 137 health markers were assessed, categorised into metabolic markers (n = 42), cardiovascular markers (n = 32), anthropometric measures (n = 19), quality of life indices (n = 10), inflammatory biomarkers (n = 10), renal and hepatic markers (n = 9), psychosocial and behavioural measures (n = 8), pulmonary function (n = 3), total mortality (n = 2), ovulatory function (n = 1), and muscle strength (n = 1). Overall, 60% of studies reported improvements, 37% found no change or mixed results, and 3% observed a worsening of health markers or indices. Based on the available data, 87% of participants (n = 15,839) in the studies reported improvements in health markers or indices as a result of low-level weight loss. Our findings suggest that low-level weight loss can lead to various health benefits and challenges the conventional threshold for effective weight loss.Preregistration The review protocol was pre-registered with PROSPERO (CRD42023406342).

Addition of neutrophil-to-lymphocyte ratio to Pre-DAA FIB-4 does not increase prediction value for de novo liver complications in hepatitis C

Background and aimsDirect-acting antiviral agents (DAAs) achieve high sustained virologic response (SVR) in chronic hepatitis C patients; yet a proportion of patients still experience de novo liver complications after SVR. Identification of risk factors is clinically important. FIB-4 index is a useful noninvasive tool to assess fibrosis, while neutrophil-to-lymphocyte ratio (NLR) is a biomarker for systemic inflammation. Our study aimed to investigate whether the addition of NLR can increase the prediction power of pre-DAA FIB-4 for de novo liver complications after SVR. MethodsWe recruited patients via The Taiwan HCV Registry (TACR) and National Health Insurance Registry Database. The inclusion criteria were patients who achieved SVR12 after DAA and were followed for at least 24 months after SVR12. Liver complications included ascites, hepatic encephalopathy, variceal bleeding, and HCC. ResultsTotally 7657 patients were recruited from 2013 to 2018. Among them, 3674 patients (48.0%) had a FIB-4 value > 3.25 and 491 patients (6.4%) had a NLR >4 before DAA. After two-year of follow-up after SVR 12, 214 patients (2.8%) developed de novo liver complications. Factors associated with liver complications included male gender, diabetes mellitus, hyperlipidemia, chronic kidney disease, and pre-DAA FIB-4 >3.25 in multivariate analyses. Addition of NLR slightly did not increase the power of predicting liver complications. ConclusionsThe overall incidence of de novo liver complications after SVR is low during short-term follow-up. Elevated pre-DAA FIB-4 is associated with de novo liver complications after SVR, whereas the addition of pre-DAA NLR does not increase the prediction power.

An inflammatory cytokine signature predicts IgA nephropathy severity and progression.

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, resulting in end-stage renal disease and increased mortality rates. Prognostic biomarkers reflecting molecular mechanisms for effective IgAN management are urgently needed. Analysis of kidney single-cell transcriptomic sequencing data demonstrated that IgAN expressed high-expression levels of inflammatory cytokines TNFSF10, TNFSF12, CCL2, CXCL1, and CXCL12 than healthy controls (HCs). We also measured the urine proteins in 120 IgAN (57 stable and 63 progressive) and 32 HCs using the proximity extension assay (PEA), and the multivariable and least absolute shrinkage and selection operator (LASSO) logistic regression analysis both revealed that CXCL12, MCP1 were the prognostic significant variables to predict IgAN progression severity. These two proteins exhibited negative correlation with the estimated glomerular filtration rate (eGFR) and patients with higher expression levels of these two proteins had a higher probability to have poorer renal outcome. We further developed a risk index model utilizing CXCL12, MCP1, and baseline clinical indicators, which achieved an impressive area under the curve (AUC) of 0.896 for prediction of IgAN progression severity. Our study highlights the significance of the inflammatory protein biomarkers for noninvasive prediction of IgAN severity and progression, offering valuable insights for clinical management.