Changes In Inflammatory Markers Research Articles

Adipose tissue biology and effect of weight loss in women with lipedema.

Lipedema is a lipodystrophic disease that is typically characterized by a marked increase in lower-body subcutaneous adipose tissue that is purported to have increased inflammation and fibrosis, impaired microvascular/lymphatic circulation and to be resistant to reduction by weight loss therapy. However, these outcomes have not been adequately studied. We evaluated body composition, insulin sensitivity, metabolic health and adipose tissue biology in women with obesity and lipedema (Obese-LIP) before and after moderate (~9%) diet-induced weight loss. At baseline, people with Obese-LIP had ~23% greater leg fat mass, ~11% lower android-to-gynoid ratio and ~48% greater insulin sensitivity (all P<0.05) than women matched on age, BMI and whole-body adiposity. In Obese-LIP, macrophage content and expression of genes involved in inflammation and fibrosis were greater, whereas lymph/angiogenesis-related genes were lower in thigh than abdominal subcutaneous adipose tissue. Weight loss improved insulin sensitivity and decreased total fat mass, with similar relative reductions in abdominal and leg fat masses, but without changes in markers of inflammation and fibrosis. These results demonstrate that affected adipose tissue in women with lipedema is characterized by increased inflammation and fibrogenesis, and alterations in lymphatic and vascular biology. Moderate diet-induced weight loss improves metabolic function and decreases lower-body adipose tissue mass.

Systemic Administration of a Site-Targeted Complement Inhibitor Attenuates Chronic Stress-Induced Social Behavior Deficits and Neuroinflammation in Mice

Chronic stress, a risk factor for many neuropsychiatric conditions, causes dysregulation in the immune system in both humans and animal models. Additionally, inflammation and synapse loss have been associated with deficits in social behavior. The complement system, a key player of innate immunity, has been linked to social behavior impairments caused by chronic stress. However, it is not known whether complement inhibition can help prevent neuroinflammation and behavioral deficits caused by chronic stress. In this study, we investigated the potential of a site-targeted complement inhibitor to ameliorate chronic stress-induced changes in social behavior and inflammatory markers in the prefrontal cortex (PFC) and hippocampus. Specifically, we investigated the use of C2-Crry, which comprises a natural antibody-derived single-chain antibody (ScFv) targeting domain-designated C2, linked to Crry, a C3 activation inhibitor. The C2 targeting domain recognizes danger-associated molecular patterns consisting of a subset of phospholipids that become exposed following cell stress or injury. We found that systemic administration of C2-Crry attenuated chronic stress-induced social behavioral impairments in mice. Furthermore, C2-Crry administration significantly decreased microglia/macrophage and astrocyte activation markers in the PFC and hippocampus. These findings suggest that site-targeted complement inhibition could offer a promising, safe, and effective strategy for treating chronic stress induced behavioral and immune function disorders.

Volume and Distribution of Early Knee Effusion After TKA with a PEEK-Based Knee Prosthesis

Background: Early knee effusion is a common phenomenon after total knee arthroplasty (TKA), with potential clinical implications. Unlike traditional alloy knee prostheses, the polyetheretherketone (PEEK) knee system has radiographic transparency on magnetic resonance (MR) scans, which allows analysis of prosthetic knee effusion. We aimed to identify the distribution and volume of knee effusion after TKA with the PEEK prosthesis with use of MR imaging and to analyze whether dynamic changes in effusion were correlated with serum inflammatory marker changes and knee function recovery. Methods: Nine patients with osteoarthritis who were 59 to 74 years old underwent unilateral TKA with the PEEK prosthesis between June 2021 and August 2021. Dynamic early postoperative changes in the volume and distribution of knee effusion were evaluated with use of 3D MR stereoscopic images. Serum inflammatory markers were measured via blood tests, and joint function was evaluated with use of the subjective functional score of the Knee Society Score (KSS) and knee range of motion (ROM). Linear regression analyses were performed to assess for correlations between knee effusion volume and inflammatory markers and between knee effusion volume and joint function. Results: The mean serum inflammatory marker levels increased significantly at 1 week after TKA with the PEEK prosthesis and then gradually decreased with time from 1 to 6 months. The mean total knee effusion volume gradually decreased over time. Concurrently, the mean KSS subjective functional score and mean knee ROM improved with time. Total knee effusion volume was positively correlated with C-reactive protein level (R2 = 0.16; p = 0.007) and negatively correlated with the change in KSS score between the preoperative and postoperative time points (R2 = 0.19; p = 0.003). Using the 1-week total knee effusion volume as a reference, a positive correlation was observed between the reduction in total knee effusion volume and the actual value of the ROM (R2 = 0.36; p = 0.0001) from 3 to 24 months postoperatively. Conclusions: Through 3D MR imaging, the precise distribution and volume of, and dynamic changes in, knee effusion after TKA with the PEEK prosthesis were confirmed and were found to be correlated with inflammation and joint function in the early postoperative period. The results demonstrate the potential clinical benefit of the PEEK-based knee system for future use. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The effects of Omega-3 fatty acids and vitamin D supplementation on the quality of life and blood inflammation markers in newly diagnosed breast cancer women: An open-labelled randomised controlled trial

Background and aimsNutritional intervention is one of the primary steps to improvement of health status and quality of life (QoL) in patients with cancer treated by chemotherapy. There is limited evidence on the potential nutritional intervention to complement active oncological treatment strategies in breast cancer (BC) patients in developing countries. The aim of the present study was to assess the effects of omega-3 fatty acids (ω3) and vitamin D3 (VitD) supplementations on the QoL and blood inflammation markers of tumor necrosis factor-alpha (TNF-α) and high-sensitive C-reactive protein (hsCRP) assessed among women newly diagnosed with BC in the Gaza Strip, Palestine MethodsA total of 88 BC women were randomly assigned into one of four groups: i) omega-3 fatty acid (ω3) group; ii) vitamin D (VitD) group; iii) ω3+VitD group, and iv) the control. Participants were received either two 300mg ω3 capsules daily, or one 50,000IU VitD tablet weekly, or both supplementation for 9-weeks. The QoL status was assessed by the European Organization for Research and Treatment of Cancer (EORTC) instruments of QLQ-C30 and QLQ-BR23 tools, while blood inflammatory markers of TNF-α hsCRP were used. All measurements were taken from baseline to the end of the intervention period. The detailed procedures of the present study were registered on ClinicalTrial.gov with the identifier NCT05331807. ResultsAt the end of the trial, participants in the ω3+VitD group showed a significant increase in overall global health status (p <0.01) compared to other groups. Additionally, this group showed significantly higher functional scores (all p <0.05) and lower scores for fatigue (p <0.01), nausea and vomiting, pain, and appetite loss (all p <0.05) at the end of the trial compared to baseline. Furthermore, comparisons between the intervention groups revealed a significant difference in blood concentrations of TNF-α and hsCRP (p <0.05). These significant differences were identified in hsCRP between ω3 and control groups (p <0.01). The ω3+VitD group demonstrated a significant reduction in both hsCRP and TNF-α levels (both p <0.05) from baseline. No significant changes in blood inflammatory markers were observed within the ω3 or VitD groups alone. ConclusionParticipants receiving daily ω3 and weekly VitD supplementation for 9 weeks showed a significant improved in QoL and blood inflammation markers among the newly diagnosed BC during their chemotherapy treatment.

Carnosine Supplementation Has No Effect on Inflammatory Markers in Adults with Prediabetes and Type 2 Diabetes: A Randomised Controlled Trial.

In vitro studies suggest that carnosine reduces inflammation by upregulating anti-inflammatory mediators and downregulating pro-inflammatory cytokines. However, human clinical trials examining the effects of carnosine on inflammatory biomarkers are scant. We conducted a secondary analysis of a double-blind randomised controlled trial (RCT) to examine the effects of carnosine supplementation on inflammatory markers and adipokines in participants with prediabetes or well-controlled type 2 diabetes (T2D). Out of 88 participants who were recruited, 49 adults with prediabetes or well-controlled T2D (HbA1c: 6.6 ± 0.7% [mean ± SD]) who were treated with diet and/or metformin were eligible for inclusion. Participants were randomised to receive 2 g/day of carnosine or a matching placebo for 14 weeks. We measured serum concentrations of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, IL-10, C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), adiponectin, leptin, adipsin, serpin, and resistin levels at baseline and after 14 weeks. The trial was registered at clinicaltrials.gov (NCT02917928). Forty-one participants (M = 29/F = 12) aged 53 (42.6, 59.3) years [median (IQR)] completed the trial. After 14 weeks of supplementation, changes in pro- and anti-inflammatory cytokine and adipokine levels did not differ between the carnosine and placebo groups (p > 0.05 for all). The results remained unchanged after adjustment for confounders including age, sex, and anthropometric measures (e.g., body fat percentage and visceral adipose tissue). In individuals with prediabetes and well-controlled T2D, carnosine supplementation did not result in any significant changes in inflammatory markers. Larger RCTs with longer follow-up durations are needed to evaluate whether carnosine may be beneficial in individuals with poorly controlled T2D.

Impact of antiplatelets, anticoagulants and cyclic nucleotide stimulators on neutrophil extracellular traps (NETs) and inflammatory markers during COVID-19.

While the association between coronavirus disease-19 (COVID-19) and neutrophils extracellular traps (NETs) is recognized, uncertainties remain regarding its precise onset, timing of resolution and target therapy. To assess changes in inflammatory and NET markers during the first week of COVID-19 hospitalization, and the association with disease severity. "In vitro" experiments investigated the effect of antiplatelets, anticoagulants, and cyclic nucleotide stimulators on NETs release. Prospective cohort study, changes in interleukin (IL)-6, IL-8, IL-17, TNF-α, RANTES, PF4, and citrullinated-H3 (citH3) levels within each outcome group was evaluated using ANOVA. Differences between moderately ill, critically ill, and non-survivors were determined using Kruskal-Wallis and logistic regression. Healthy neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) or COVID-19 sera and treated with unfractionated heparin (UFH), low molecular weight heparin (LMWH), aspirin (ASA), ticagrelor, cinaciguat, sildenafil, and milrinone. The proportion of NETosis was assessed using IncuCyte Cell Imager. Of the 125 patients, 40.8% had moderate COVID-19, 40.8% had critical COVID-19 but recovered, and 18.4% died. From admission to hospitalization day 8, IL-6 levels decreased in moderately and critically ill, but not in non-survivors, while citH3 levels increased in critically ill and non-survivors. IL-6, IL-8, and TNF-α levels were associated with critical and fatal COVID-19. The release of NETs by neutrophils stimulated with PMA or COVID-19 sera was decreased in the presence of ASA, UFH, LMWH and cyclic nucleotide stimulators in a dose-dependent manner. In the first week of hospitalization, NET markers rose later than inflammatory markers in severe COVID-19 cases. Cyclic nucleotide stimulators, ASA and heparin may emerge as treatment approaches as they may modulate NETosis.

Single and consecutive 10-day remote ischemic preconditioning modify physical performance, post-exercise exerkine levels, and inflammation.

Remote ischemic preconditioning (RIPC) is a method of protection against induced ischemia reperfusion injury, and an increasing number of studies showed some of its inconclusive ergogenic effects in sports. RIPC involves short cycles of cuff inflation followed by its deflation which may affect many body systems. While most of the studies focus on single RIPC effects, there is insufficient data regarding training-like repeated RIPC interventions. Thus, in this study, we analyzed the effect of a single- and consecutive 10-day RIPC procedure on a single leg, focusing on the exerkine levels and changes in inflammation markers following the Wingate Anaerobic Test (WAnT). Two single-blinded, sham-controlled protocols were designed to evaluate the 1) single (crossover study) and 2) consecutive 10-day (parallel study) RIPC effects on the WAnT performance and exercise-induced lactate, glucose, exerkine, and inflammation markers (BDNF; IL-6; IL-10; IL-15; LIF; oncostatin M). In each protocol, 37 physically active men (19.98 ± 1.17 years) were randomly assigned into two groups according to a particular study design. An increase in participants' mean (4.81%, p < 0.05) and peak power (6.25%, p < 0.05) during the WAnT was observed only after the consecutive 10-day RIPC. Similarly, a significant 15.5% (p < 0.05) decrease in the IL-6 concentration 120 min after the WAnT was observed only in the consecutive 10-day RIPC protocol, as well as a 12.2% (p < 0.01) increase in oncostatin M 60 min after the WAnT. The results demonstrate the efficacy of the consecutive 10-day RIPC procedure in modulating exercise performance and post-exercise inflammation markers.

Impact of remimazolam on postoperative inflammatory markers and complications in thoracoscopic pulmonary lobectomy patients: A retrospective analysis.

Remazolam is widely used for procedural sedation in intensive care units. It has been shown to have anti-inflammatory and organ-protecting properties. However, the changes in inflammatory markers and analgesic effects of remazolam after thoracoscopic pulmonary lobectomy remain unclear. This study aims to assess the effects of the novel drug remimazolam on inflammatory factor levels and postoperative complications in thoracoscopic pulmonary lobectomy patients, providing a scientific basis for clinical use. This retrospective study analyzed 200 thoracoscopic pulmonary lobectomy patients, who were divided into a control group and a remimazolam group based on their anesthesia method. Patients in ramazolam group were anesthetized with ramazolam, while patients in control group were anesthetized with propofol. All patients were performed by the same physician team and anesthesia team. Inflammatory factors (including interleukin-6 [IL-6], C-reactive protein [CRP], including interleukin-8) were measured preoperatively and postoperatively, and postoperative complication rates were compared between the 2 groups. The levels of IL-6 and CRP were significantly higher in the remimazolam group at 7 days postoperatively compared to the control group. No significant differences were observed in preoperative inflammatory factors or postoperative including interleukin-8 levels between the 2 groups. Additionally, there were no significant differences in the overall incidence of postoperative complications or in specific complications such as pulmonary infection, atelectasis, subcutaneous emphysema, pneumothorax, surgical site infection, and arrhythmia. Patients receiving remimazolam had higher postoperative IL-6 and CRP levels compared to the control group, without an increase in postoperative complications. In clinical use, attention should be paid to the control of inflammatory indicators in patients using remazolam. However, due to potential confounding factors and the retrospective design, we cannot establish a causal relationship between remimazolam and elevated inflammatory markers. These findings suggest a possible association that requires cautious interpretation. Further research is needed to assess the clinical relevance and explore the underlying mechanisms.

Systemic Immune-Inflammatory Index and Other Inflammatory Marker Variations in Oral Squamous Cell Carcinoma Management.

Background and Objectives: With the greatest rate of morbidity and death, OSCC is one of the world's most critical public health problems. Being a complex pathology, the management process that includes diagnostic, surgical, and adjuvant treatments must as well take into account the involvement of the immune system. This study aims to evaluate various biomarkers such as neutrophils, lymphocytes, platelets, SII, and NLR in the different stages of OSCC treatment and in correlation with TNM stages, in order to observe the inflammatory response of the host. Materials and Methods: A total of 154 patients diagnosed with OSCC were included in the present retrospective study. Routine blood samples were collected from all patients both before and after surgery. Using the detected values of platelets, neutrophils, and lymphocyte count, the systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) were calculated. Based on the oncologist's recommendation, 46 patients underwent adjuvant radiotherapy as part of their oncologic treatment plan. For these patients, additional blood samples were collected before the first and after the last radiotherapy session for determining the values of platelets, neutrophils, and lymphocyte count, and SII and NLR calculation. Results: Prior to the first radiotherapy session, neutrophils decreased slightly to 4.35, lymphocytes increased to 2.23, and platelets rose to 258.62. The SII and NLR were 641.02 and 2.19, respectively. Following the last radiotherapy session, neutrophils increased substantially to 10.30, while lymphocytes decreased to 1.21. Platelets showed a slight reduction to 227.08. Notably, the SII rose dramatically to 3084.19, and the NLR increased significantly to 15.49, suggesting an important immune and inflammatory response of the host. Conclusions: The host's immunological and inflammatory responses are impacted by both surgery and adjuvant radiation administered following surgery. The parameters assessed-neutrophils, lymphocytes, platelets, SII, and NLR-qualify as significant variables that need to be monitored before, during, and following OSCC therapy. This study's findings validated significant changes in immunological and inflammatory markers in the management of OSCC.

Changes in anthropometry, adiposity, and inflammation in Black and White women engaged in intentional weight loss.

We examined associations among changes in anthropometry, regional adiposity, and inflammatory markers in Black and White women participating in intentional weight loss. A total of 104 women with BMI ≥ 25 kg/m2 self-selected bariatric surgery (n = 66) or a diet and exercise program (n = 38). Anthropometric, dual-energy x-ray absorptiometry-quantified regional adiposity, and inflammatory markers (C-reactive protein [CRP], tumor necrosis factor α [TNF-α], soluble TNF receptor I [sTNFRI], sTNFRII, interleukin [IL]-6, and soluble IL-1 receptor antagonist) were measured at baseline and 6 months. Weight, BMI, visceral adipose tissue, and regional (android and gynoid) adiposity declined in the bariatric surgery group. Among bariatric surgery participants, Black women experienced declines of lesser magnitude in terms of weight and BMI than White women, but changes in regional adiposity and visceral adipose tissue did not differ. In the bariatric surgery group, decreases in weight and BMI were associated with decreases in CRP and IL-6 among White women, but not Black women. Decreases in weight, BMI, and android fat were associated with increases in TNF-α, sTNFRI, and sTNFRII among Black women, but not White women. Decreases in anthropometry and adiposity were observed among Black and White bariatric surgery participants; however, associations among changes in adiposity, anthropometry, and inflammation differed by race.

Sex-Specific Associations Between Leucocyte Measures and Obstructive Sleep Apnea in Han Chinese.

White blood cell (WBC) and its subset counts are standard, inexpensive, direct markers of inflammation. Obstructive sleep apnea (OSA) is implicated in changes in inflammation markers, and sex differences are evident in both OSA and inflammation. It is unknown whether sex modulates the relationship between OSA severity and leukocyte measures. 1222 patients (914 males, 308 females) underwent overnight laboratorial polysomnography and measurement of WBC and its subset (lymphocyte, neutrophil, monocyte) counts. Patients were divided into primary snoring and mild, moderate, and severe OSA groups, and differences in leukocyte parameters were analyzed separately by sex in multivariable analyses. In multiple regression models, higher apnea-hypopnea index (AHI) was independently associated with neutrophil counts only in men, and with higher total WBC, lymphocyte and monocyte counts both in women and men. Further ordinal logistic regression analysis revealed a significant association between AHI and total WBC (OR 1.87, 95% CI 1.09-3.23) and neutrophil (OR 1.77, 95% CI 1.02-3.07) counts in men only. Correlation analysis also revealed more robust relationships between leukocyte measures and cardiometabolic risk markers in men than in women. This study provides novel data suggesting a significant association between neutrophil count and OSA severity only in men but not women. Similarly, the relationship between leukocyte parameters and cardiometabolic risk markers were more pronounced in men than women. Our findings suggest a sex-specific impact of OSA on leukocyte measures and on their relationship with indices of cardiometabolic risk.

Weight neutral early time-restricted eating improves glycemic variation and time-in-range without changes in inflammatory markers.

Weight neutral early time-restricted eating improves glycemic variation and time-in-range without changes in inflammatory markers.

Outcomes and inflammation changes in different types of immunocompromised patients with critically ill COVID-19 admitted to ICU: a national multicenter study

BackgroundImmunocompromised patients face higher risks of Severe Acute Respiratory Syndrome Coronavirus 2 infection and co-infections, leading to a possibility of high disease severity and poor outcomes. Conversely, immunosuppression can mitigate the excessive inflammatory response induced by the virus, potentially reducing disease severity. This study aims to investigate the prognostic differences and early inflammatory response characteristics in various types of immunocompromised patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU), summarize their clinical features, and explore potential mechanisms.MethodsA retrospective analysis was conducted on critically ill COVID-19 patients admitted to the ICU of 59 medical centers in mainland China during the Omicron outbreak from November 2022 to February 2023. Patients were categorized into two groups based on their immunosuppression status: immunocompromised and immunocompetent. Immunocompromised patients were further subdivided by etiology into cancer patients, solid organ transplant (SOT) patients, and other immunocompromised groups, with immunocompetent patients serving as controls. The mortality rates, respiratory support, complications, and early inflammatory cytokine dynamics upon ICU admission among different populations were analyzed.ResultsA total of 2030 critically ill COVID-19 patients admitted to ICU were included, with 242 in the immunocompromised group and 1788 in the immunocompetent group. Cancer patients had a higher median age of 69 years (IQR 59, 77), while SOT patients were generally younger and had less severe illness upon ICU admission, with a median APACHE II score of 12.0 (IQR 8.0, 20.0). Cancer patients had a twofold increased risk of death (OR = 2.02, 95% CI 1.18–3.46, P = 0.010) compared to immunocompetent patients. SOT and cancer patients exhibited higher C-reactive protein and serum ferritin levels than the immunocompetent group in their early days of ICU admission. The CD8+ T cells dynamics were inversely correlated in cancer and SOT patients, with Interleukin-6 levels consistently lower in the SOT group compared to both immunocompetent and cancer patients.ConclusionCritically ill COVID-19 patients admitted to the ICU exhibit distinct clinical outcomes based on their immunosuppression status, with cancer patients facing the highest mortality rate due to variations in inflammatory responses linked to their immunosuppression mechanisms. Monitoring dynamic changes in inflammatory markers and immune cells, particularly CD8+ T lymphocytes and IL-6, may offer valuable prognostic insights for these patients.

Impact of combining ablation index-guided and very high-power short-duration ablation at posterior wall adjacent to esophagus during perioperative period on procedural factors.

The impact of combining ablation index (AI)-guided and very high-power short-duration (vHPSD) ablation on procedural factors at the posterior wall near the esophagus is unclear. Atrial fibrillation patients who underwent initial ablation using three-dimensional mapping were enrolled. Patients were classified into two groups: those who underwent only AI-guided pulmonary vein isolation (PVI) (AI group) and those who underwent vHPSD ablation at the posterior wall adjacent to the esophagus in addition to AI-guided PVI (AI + vHPSD group). Differences in myocardial injury, inflammation, procedural characteristics, and pulmonary vein (PV) reconnection patterns were assessed between the two groups. This study included 167 patients (AI group, 83 patients; AI+vHPSD group, 84 patients). No significant differences in high-sensitive troponin I or changes in inflammatory markers between pre- and Postablation were observed in either group. Total application time and total application energy were significantly lower in the AI+vHPSD group than in the AI group (p < 0.001 for both) despite no significant difference in the total number of applications between the groups. The incidence of esophagus temperature ≥40 degrees was significantly lower in the AI+vHPSD group than in the AI group (p = 0.036). However, the incidence of PV reconnections near the esophagus was significantly higher in the AI+vHPSD group than in the AI group (11.9% vs 3.6%, p = 0.046), despite no significant difference in the incidence of PV reconnections overall. The combination of AI-guided PVI and vHPSD adjacent to the esophagus demonstrated reduced application energy requirements and maintained safety and effectiveness during the perioperative period.

Weight Loss, Pathological Changes, and Inflammatory Effects from a Short-Term Ketogenic Diet in Overweight and Obese Men with Untreated Prostate Cancer on Active Surveillance.

Active Surveillance (AS) is a favored strategy for the management of indolent prostate cancers (PCs). Overweight and obese men harbor an increased risk of cancer progression during AS. We aim to prospectively evaluate the feasibility and outcomes of a ketogenic diet (KD) weight-loss intervention in overweight men with PC. Men with PC and a BMI > 25 kg/m2 undergoing AS were placed on an 8-week ad libitum KD program before a scheduled surveillance biopsy to assess the impact on clinical grade group (CGG). Blood ketone levels were tracked to ensure compliance. BMI, PSA, and inflammatory marker data (TNF-α, TNFR1, TNFR2, sICAM-1, sVCAM-1, IL-6, IL1-RA, CRP, and SAA) were collected before and after the KD intervention. A Shapiro-Wilk test was performed to assess the normality of all continuous study variables. Paired t-tests and Wilcoxon rank sum tests were utilized to compare normally and non-normally distributed study outcomes, respectively. Ten AS patients aged 62.1 (±5.4) years were enrolled with an average BMI of 31.7 kg/m2 (±11.8). Post-KD intervention mean blood ketone levels were 0.32 (±0.12) mmol/L with a mean BMI reduction of 7.4% (p < 0.0003). There were no meaningful changes in PSA or inflammatory biomarkers (p > 0.05). Nine patients completed re-biopsy following a KD with four patients showing no evidence of cancer; one downgraded to a lower CGG; two had unchanged CGG scores; and two had higher CGG scores compared to baseline. Short-term KD interventions for BMI reduction are feasible in men undergoing AS for PC and may result in favorable pathological effects without inflammatory marker changes. Larger studies with longer follow-up are needed to explore whether KD-induced weight loss can improve clinical outcomes with AS in PC.

The Efficacy and Safety of NOVAponin (Dolichos lablab Linne Extract Powder) in Mild Functional Dyspepsia: A Single-center, Randomized, Double-Blind, Placebo-controlled Study.

NOVAponin, a functional health food derived from Dolichos lablab Linne extract improves gastric mucosal injury and increases regeneration and proliferation. This study aims to investigate the efficacy and safety of NOVAponin in individuals with mild functional dyspepsia (FD). In this single-center, double-blind, randomized clinical trial, 131 patients with FD meeting the Rome IV criteria were enrolled. Changes in the gastrointestinal symptom rating scale (GSRS), FD-related quality of life (FD-QoL), gastrointestinal symptom (GIS) scores, inflammatory and anti-inflammatory markers, and adverse effects before and after administration were compared. After 12 weeks of administration, GSRS upper abdominal symptom scores were significantly improved in the test group compared to the control group (-5.30 ± 0.60 vs -2.35 ± 0.56, P < 0.001). GSRS upper abdominal symptom scores (-5.13 ± 0.55 vs -1.92 ± 0.44, P < 0.001), GSRS total scores (-7.02 ± 0.91 vs -3.33 ± 0.73, P < 0.001), GIS total scores (-11.21 ± 0.53 vs -6.65 ± 0.70, P < 0.001) after 6 weeks of administration, GSRS total scores (-7.54 ± 0.94 v. -3.31 ± 0.85, P < 0.001), GIS total scores (-11.90 ± 0.52 vs -7.61 ± 0.73, P < 0.001), and FD-QoL total scores (-11.41 ± 1.75 vs -5.55 ± 1.20, P = 0.007) after 12 weeks of administration also showed significant differences between groups. The differences were slightly more pronounced in epigastric pain syndrome subtypes and in females than the others, although more females were assigned to the test group. There were no significant changes in inflammatory and anti-inflammatory markers or adverse reactions. NOVAponin significantly improved mild FD symptoms especially in epigastric pain syndrome subtype and in females, and was found to be safe.

Renal Inflammation, Oxidative Stress, and Metabolic Abnormalities During the Initial Stages of Hypertension in Spontaneously Hypertensive Rats.

Background: Hypertension is a major cause of mortality worldwide. The kidneys play a crucial role in regulating blood pressure and fluid volume. The relationship between the kidneys and hypertension is complex, involving factors such as the renin-angiotensin system, oxidative stress, and inflammation. This study aims to assess the levels of inflammatory markers, oxidative stress, and metabolic factors in the kidneys, focusing on their potential role in early renal damage and their association with the development of hypertension. Methods: This study was designed to compare the levels of selected inflammatory markers, e.g., interleukins, tumor necrosis factor-α (TNF-α), transforming growth factor, and serine/threonine-protein (mTOR); oxidative stress markers such as malondialdehyde, sulfhydryl group, and glucose (GLC); and metabolic markers among other enzymes, such as alanine transaminase (ALT), aspartate transaminase (AST), hexokinase II (HK-II), and hypoxia-inducible factor-1α (HIF-1α), as well as creatinine in the kidneys of spontaneously hypertensive rats (SHR/NCrl, n = 12) and Wistar Kyoto rats (WKY/NCrl, n = 12). Both juvenile (5 weeks old) and maturing (10 weeks old) specimens were examined using spectrophotometric methods, e.g., ELISA. Results: Juvenile SHRs exhibited reduced renal levels of all studied cytokines and chemokines, with lower oxidative stress and deficits in the mTOR and HK-II levels compared to the age-matched WKYs. Maturing SHRs showed increased renal levels of interleukin-1β (IL-1β), IL-6, IL-18, and TNF-α, alongside elevated carbonyl stress and increased HIF-1α as opposed to their control peers. The levels of all other studied markers were normalized in these animals, except for ALT (increased), ALP, and GLC (both reduced). Conclusions: This study underscores the significant impact of inflammatory, oxidative stress, and metabolic marker changes on renal function. Juvenile SHRs display lower marker levels, indicating an immature immune response and potential subclinical kidney damage that may contribute to hypertension development. In contrast, mature SHRs exhibit chronic inflammation, oxidative dysregulation, and metabolic disturbances, suggesting cellular damage. These changes create a feedback loop that worsens kidney function and accelerates hypertension progression, highlighting the kidneys' crucial role in both initiating and exacerbating this condition.

Effects of probiotics and fibers on markers of nephropathy, inflammation, intestinal barrier dysfunction and endothelial dysfunction in individuals with type 1 diabetes and albuminuria. The ProFOS Study

AimsTo estimate whether a mix of pre- and probiotics would strengthen the gut barrier and protect the kidneys in individuals with type 1 diabetes and albuminuria. MethodsRandomized, placebo-controlled, crossover study. Forty-one participants received synbiotic (pre- and probiotics) mix or placebo for 12 weeks with 6 weeks washout. Primary endpoint was change from baseline to end-of-period in UACR. Secondary endpoints were changes in endothelial glycocalyx thickness, inflammatory and intestinal barrier dysfunction markers, glomerular filtration rate (GFR) and ambulatory systolic blood pressure. ResultsThirty-five participants completed the study. Mean age was 58 (SD 10) years, 73 % (n = 30) were male, median UACR was 134 (IQR 63–293) mg/g, estimated GFR was 75 (30) ml/min/1.73m2. There was no significant difference in UACR with a mean relative change (CI 95 %) from baseline to end-of-treatment of −3.0 (−18.4; 15.5) % in the synbiotic group and −12.0 (−29.6; 9.6) % in the placebo group with no significant difference between treatment periods (9.37 (−25.2; 44.0) percentage points; p = 0.60). No significant beneficial difference in the secondary end points was demonstrated. ConclusionTwelve weeks treatment with synbiotic mix had no effect on UACR or on any of the secondary endpoints in subjects with type 1 diabetes and albuminuria.

Novel pilot study on plasma metabolites and biomarkers in a rat model of silica-induced lung inflammation and fibrosis

Silica-induced lung damage may be associated with changes in distinct metabolites potentially serving as biomarkers. Due to the lack of metabolomic data from animal models, this pilot study aimed to evaluate changes in markers of inflammation and fibrosis, as well as plasma metabolites in rats at 14 and 28 days after silica instillation.Adult male Wistar rats were administered a single oropharyngeal intratracheal dose of silica suspension or sterile saline in controls. Selected markers of inflammation, oxidative stress, fibrosis, and cell counts in blood and bronchoalveolar lavage fluid have been evaluated. Finally, plasma metabolites were detected using a targeted metabolomics approach with an MxP® Quant 500 kit.Silica instillation induced noticeable inflammatory, oxidative, and fibrotic changes in lung tissue within the first 14 days. During the next two weeks, the shifts in some markers were further accentuated. After exposure to silica, the metabolomic analysis identified significant changes in metabolites associated with lipid metabolism, biogenic amines, amino acid derivatives, carboxylic acids, bile acids, putrescine, glycosylceramides, and acylcarnitines.This pilot study provides initial evidence that significant alterations in plasma metabolite profiles accompany silica-induced lung injury in rats. These findings suggest a possible systemic impact, particularly on lipid metabolism, and indicate the urgent need for a deeper understanding of the metabolic reprogramming associated with silica-induced lung injury to pave the way for the discovery of novel biomarkers.

The Impact of RNA Interference on Atherosclerotic Plaque Progression: A Meta-Analysis of Preclinical Studies

Background: Atherosclerosis, a chronic inflammatory disease characterized by the buildup of plaque within arteries, remains a leading cause of cardiovascular morbidity and mortality. RNA interference (RNAi) has emerged as a promising therapeutic strategy for atherosclerosis by targeting genes involved in plaque formation and progression. This meta-analysis aimed to evaluate the efficacy of RNAi in preclinical models of atherosclerosis. Methods: A systematic search of PubMed, Embase, and Web of Science databases was conducted from January 2013 to December 2023 to identify preclinical studies investigating the impact of RNAi on atherosclerotic plaque progression. Studies utilizing various RNAi modalities (siRNA, miRNA mimics/inhibitors, shRNA) targeting different genes involved in atherosclerosis were included. The primary outcome was plaque size reduction. Secondary outcomes included changes in plaque composition, lipid profiles, and inflammatory markers. A random-effects model was used to pool data and calculate standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Results: Seven preclinical studies met the inclusion criteria, encompassing a total of 210 animals. RNAi interventions significantly reduced atherosclerotic plaque size compared to controls (SMD -1.51; 95% CI -2.36 to -0.66; p&lt;0.00001; I²=12%). Analysis of secondary outcomes revealed favorable effects of RNAi on plaque composition, with a significant decrease in lipid content and an increase in collagen content. Furthermore, RNAi significantly improved lipid profiles by reducing total cholesterol and LDL-cholesterol levels. A significant reduction in inflammatory markers, such as TNF-α and IL-6, was also observed. Conclusion: This meta-analysis provides compelling evidence supporting the therapeutic potential of RNAi in attenuating atherosclerotic plaque progression in preclinical models. RNAi effectively reduced plaque size, improved plaque stability, and modulated lipid metabolism and inflammation.