Markers Of Inflammatory Response Research Articles

Acute inflammatory response following lower-and upper-body Wingate anaerobic test in elite gymnasts in relation to iron status

Introduction: Artistic gymnastics is one of the most demanding sports disciplines, with the athletes demonstrating extremely high levels of explosive power and strength. Currently, knowledge of the effect of gymnastic training adaptation on exercise-induced inflammatory response is limited. The study aimed to evaluate inflammatory response following lower- and upper-body high-intensity exercise in relation to the iron status in gymnasts and non-athletes. Methods: Fourteen elite male artistic gymnasts (EAG, 20.6 ± 3.3 years old) and 14 physically active men (PAM, 19.9 ± 1.0 years old) participated in the study. Venous blood samples were taken before and 5 min and 60 min after two variants of Wingate anaerobic test (WAnT), upper-body and lower-body WAnT. Basal iron metabolism (serum iron and ferritin) and acute responses of selected inflammatory response markers [interleukin (IL) 6, IL-10, and tumour necrosis factor α] were analysed.Results: EAG performed significantly better during upper-body WAnT than PAM regarding relative mean and peak power. The increase in IL-6 levels after upper-body WAnT was higher in EAG than in PAM; the opposite was observed after lower-body WAnT. IL-10 levels were higher in EAG than in PAM, and tumour necrosis factor α levels were higher in PAM than those in EAG only after lower-body WAnT. The changes in IL-10 correlated with baseline serum iron and ferritin in PAM.Discussion: Overall, gymnastic training is associated with the attenuation of iron-dependent post-exercise anti-inflammatory cytokine secretion.

Associations of three differential white blood cell counts, platelet counts, and their derived inflammatory indices with cancer-related fatigue in patients with breast cancer undergoing chemotherapy.

Inflammation is thought to be a vital element in the etiology of cancer-related fatigue (CRF), and circulating blood cell parameters could be important markers of inflammatory response. However, the associations of several major blood cell counts and their derived inflammatory indices with CRF are not well described. The present study aimed to establish whether a relationship exists between the counts of three white blood cell (WBC) types, platelets, and CRF and investigate whether several systemic inflammatory indices were associated with CRF in patients with breast cancer (BC). A cross-sectional survey was conducted with a sample of 824 patients with BC undergoing chemotherapy. The cancer fatigue scale was administered to assess CRF. Hematological indicators, including neutrophils, lymphocytes, monocytes, and platelets, were retrieved from routine blood test. Network analyses were used to examine the associations among them. Among 824 participants, the mean score of CRF was (27 ± 10), ranging from 0 to 57. The results of network models indicated that physical fatigue was negatively linked to lymphocyte counts (weight = - 0.161), and affective fatigue was positively associated with neutrophil counts (weight = 0.070). Additionally, physical fatigue was positively linked to the platelet-to-lymphocyte ratio (PLR) (weight = 0.049). There were preliminary associations of counts of three WBC types, platelet counts, and systemic inflammatory indices, with distinct dimensions of CRF in patients with BC. Findings provide empirical support for the cellular basis of fatigue-associated inflammatory states.

Neutrophil/lymphocyte ratio and cognitive performances in first-episode patients with schizophrenia and healthy controls

Abnormal immune and inflammatory responses are considered to contribute to schizophrenia (SZ). The neutrophil/lymphocyte ratio (NLR) is an inexpensive and reproducible marker of systemic inflammatory responses. Accumulating studies have demonstrated that NLR values are increased in SZ compared to healthy controls and closely related to clinical symptoms in antipsychotic-naïve first-episode SZ (ANFES) patients. However, to our knowledge, only one study has examined NLR in relation to neurocognition in 27 first-episode psychosis patients and 27 controls. This study aimed to examine the relationship of NLR values with cognitive performances in ANFES patients with a larger sample size. Whole blood cell counts were measured in ninety-seven ANFES patients and fifty-six control subjects. The neurocognitive functions of all subjects were measured by the repeatable battery for the assessment of neuropsychological status (RBANS). ANFES patients performed worse on cognition and had increased NLR values relative to healthy controls. In addition, increased NLR was negatively associated with cognitive functions in ANFES patients. Lymphocyte count was positively correlated with cognitive functions in patients. These findings suggest that the abnormal immune and inflammation system indicated by NLR may be involved in the cognitive functions in ANFES patients.

Association between blood inflammatory indicators and prognosis of papillary thyroid carcinoma: a narrative review.

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer, accounting for up to 85-90% of cases, with the best overall prognosis and mostly inert tumors. However, some tumors are aggressive, causing metastasis, recurrence, and other bad outcomes. Preoperative inflammation indices, such as lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII) in peripheral blood, have recently gained attention as nonspecific markers of inflammatory response in thyroid. In this study, we reviewed the interactions between preoperative inflammatory factors and outcomes in patients with PTC. This is a narrative review. We searched for English articles published between January 2014 and December 2023 on PubMed and Web of Science to identify how do these blood indicators affect the prognosis of patients with papillary thyroid cancer. All retrievable indicators that have predictive significance for the prognosis of PTC were included, and the prognosis mainly included tumor-node-metastasis (TNM) staging, survival rate, recurrence, clinical and pathological risk factors such as lymph node metastasis (LNM), etc. From the general evidence, the prognostic predictive value of cell count alone was unknown, and low LMR was usually associated with poor prognosis, high NLR and high platelet-to-lymphocyte ratio (PLR) usually indicated poor prognosis. These minimally invasive, low-cost, and easily obtainable blood indicators provide convenience for precise prognosis management of PTC patients, but many of the findings are conflicting and need to be validated by prospective studies that are more multi-sample, multi-centre and incorporate factors such as age that affect the immune response.

Correlation between Neurotransmitters (Dopamine, Epinephrine, Norepinephrine, Serotonin), Prognostic Nutritional Index, Glasgow Prognostic Score, Systemic Inflammatory Response Markers, and TNM Staging in a Cohort of Colorectal Neuroendocrine Tumor Patients.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

Contrasting Disease Progression, Microglia Reactivity, Tolerance, and Resistance to Toxoplasma gondii Infection in Two Mouse Strains

Our study investigated the innate immune response to Toxoplasma gondii infection by assessing microglial phenotypic changes and sickness behavior as inflammatory response markers post-ocular tachyzoite instillation. Disease progression in Swiss albino mice was compared with the previously documented outcomes in BALB/c mice using an identical ocular route and parasite burden (2 × 105 tachyzoites), with saline as the control. Contrary to expectations, the Swiss albino mice displayed rapid, lethal disease progression, marked by pronounced sickness behaviors and mortality within 11–12 days post-infection, while the survivors exhibited no apparent signs of infection. Comparative analysis revealed the T. gondii-infected BALB/c mice exhibited reduced avoidance of feline odors, while the infected Swiss albino mice showed enhanced avoidance responses. There was an important increase in microglial cells in the dentate gyrus molecular layer of the infected Swiss albino mice compared to the BALB/c mice and their respective controls. Hierarchical cluster and discriminant analyses identified three microglial morphological clusters, differentially affected by T. gondii infection across strains. The BALB/c mice exhibited increased microglial branching and complexity, while the Swiss albino mice showed reduced shrunken microglial arbors, diminishing their morphological complexity. These findings highlight strain-specific differences in disease progression and inflammatory regulation, indicating lineage-specific mechanisms in inflammatory responses, tolerance, and resistance. Understanding these elements is critical in devising control measures for toxoplasmosis.

Analysis of Inflammatory Markers in Response to Induction of Reprometabolic Syndrome by a Eucaloric High Fat Diet in Normal Weight Women.

Obesity is associated with chronic low-level inflammation and is known to contribute to metabolic dysfunction and hypogonadotropic hypogonadism, which we have previously termed the 'Reprometabolic Syndrome.' To investigate potential factors involved in obesity-related reproductive endocrine dysfunction, we conducted a secondary analysis of inflammatory markers in a sample of normal weight women exposed to a one-month eucaloric high-fat diet (HFD), which, as reported earlier, induced the relative hypogonadotropic hypogonadism characteristic of Reprometabolic Syndrome. Eighteen healthy women with a BMI between 18.0-24.9kg/m2 and regular menstrual cycles participated in the study. Frequent blood sampling was performed during the early follicular phase before and after the one-month eucaloric HFD intervention (48% of calories from fat). Serum samples pooled from each participant were analyzed using immunoassay to measure levels of 30 cytokines, interleukins, and chemokines. Differences between pre- and post-HFD intervention measures were examined by one-sample t-tests. Exposure to the eucaloric HFD did not result in changes in body weight. HFD-induction of Reprometabolic Syndrome in normal weight women was associated with a significant elevation only in the anti- inflammatory cytokine IL-10 (p = 0.04). Eotaxin, IL-6 and MIP-1β also increased in response to the HFD, but not statistically significantly (p = 0.07). Results suggest that the increase in multiple inflammatory markers, typically associated with obesity, are not primary mediators of the relative hypogonadotropic hypogonadism of Reprometabolic Syndrome. Clinical Trials Registration Number: NCT02653092; Date of Registration: January 6, 2016.

Predictive value of pretreatment circulating inflammatory response markers in the neoadjuvant treatment of breast cancer: meta-analysis.

Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting the response to neoadjuvant chemotherapy in breast cancer is uncertain. A systematic review and meta-analysis of the literature was carried out to investigate this. A systematic search of electronic databases was conducted to identify studies that explored the predictive value of circulating systemic inflammatory response markers in patients with breast cancer before commencing neoadjuvant therapy. A meta-analysis was undertaken for each inflammatory marker where three or more studies reported pCR rates in relation to the inflammatory marker. Outcome data are reported as ORs and 95% confidence intervals. A total of 49 studies were included, of which 42 were suitable for meta-analysis. A lower pretreatment neutrophil-to-lymphocyte ratio was associated with an increased pCR rate (pooled OR 1.66 (95% c.i. 1.32 to 2.09); P < 0.001). A lower white cell count (OR 1.96 (95% c.i. 1.29 to 2.97); P = 0.002) and a lower monocyte count (OR 3.20 (95% c.i. 1.71 to 5.97); P < 0.001) were also associated with a pCR. A higher lymphocyte count was associated with an increased pCR rate (OR 0.44 (95% c.i. 0.30 to 0.64); P < 0.001). The present study found the pretreatment neutrophil-to-lymphocyte ratio, white cell count, lymphocyte count, and monocyte count of value in the prediction of a pCR in the neoadjuvant treatment of breast cancer. Further research is required to determine their value in specific breast cancer subtypes and to establish optimal cut-off values, before their adoption in clinical practice.

AB055. SOH24AB_245. Value of pre-treatment circulating inflammatory response markers in predicting response to neoadjuvant treatment of breast cancer: a systematic review &amp; meta-analysis

AB055. SOH24AB_245. Value of pre-treatment circulating inflammatory response markers in predicting response to neoadjuvant treatment of breast cancer: a systematic review &amp; meta-analysis

Role of Molecular Biomarkers in Endometriosis-Related Infertility: A Narrative Review of the Literature.

Endometriosis is a chronic benign inflammatory disease that affects womenof reproductive age. The clinical presentations of endometriosis include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. There is awell-established association between endometriosis and infertility. Therefore, there is a need for an early diagnosis of endometriosis-related infertility. In this study, we aim to identify the role of biomarkers as predictive factors of the presence of the disease and its severity and their correlation with the pregnancy outcome. We performed an electronic database search of all published studies in PubMed and EMBASE from January 2018 to May 2023. Numerous innovative biomarkers identified in cases of endometriosis and infertility have been studied over the past years, including micro-RNAs, BCL6 endometrial expression, cytotoxic T-lymphocyte antigen 4, human leukocyte antigen G, programmed cell death protein 1, programmed cell death ligand 1 immune checkpoint molecules, plasma fibronectin-fibrin complexes, homeobox A10 gene, systemic inflammatory response markers, uterine natural killer cells, and the eutopic endometrium proteome. Considerable research has been done to identify diagnostic biomarkers for the early detection and prevention of endometriosis-associated infertility. However, none of these biomarkers displayed enough diagnostic accuracy to be used in daily clinical practice. Future research is valuable to establish them as reliable diagnostic tools.

The Role of Leu-Enkephalin Synthetic Analogue in Regulation of Systemic Inflammatory Response and Prevention of ARDS in Severe Combined Injury

The aim of the study. To study the effect of ley-enkephalin synthetic analogue on the dynamics of inflammatory response markers and organ dysfunction in patients with severe combined trauma.Materials and methods. A prospective clinical study with historical control from two clinical centers — N. I. Pirogov State Clinical Hospital No. 1 and N.V. Sklifosovsky Clinical and Research Institute for Emergency Medicine — included men and women with severe combined trauma and the ISS scores values of 18–44, aged 18 to 70 years. Diagnostic and therapeutic approaches in all patients followed current international, national&amp; local protocols and 2022 clinical recommendations of the Russian Society of Surgeons «Combined and multiple trauma in combination with shock (Polytrauma)». In the study group, treatment was supplemented with extended (72 hours from the admission) infusion of the test drug through a syringe dispenser following the study protocol. Effects of the test drug prolonged infusion were evaluated for the following laboratory parameters: levels of cortisol, procalcitonin, interleukin 6, NTproBNP and leukocyte count. Laboratory tests were performed at 4 time points: prior to test drug infusion, 24 hours and 72 hours after initiation of infusion, and on Day 7. The study evaluated patient’s dynamics using APACHE II, SOFA and SAPS II scales and percentage of patients developing organ dysfunction (renal, respiratory, cardiovascular), rates of sepsis complications and mortality.Results. Patients who received the test drug had significantly lower concentrations of systemic inflammatory response markers, i. e. PCT (P=0.001) and IL-6 (P=0.010) after 24 hours of follow-up vs the control group patients. The incidence of ARDS has also decreased in the study group (P=0.011 vs control). Acute kidney injury (AKI) rate was insignificantly higher in the control group (P=0.349). The duration of hospital stay in the control group was 35 (17; 51) days vs 18 (14; 30) days in the study group (P=0.140)Conclusion. The use of ley-enkephalin synthetic analogue inhibits production of such key systemic inflammatory response markers as PCT and IL-6, and reduces PCT concentrations within 24 hours in patients with severe combined trauma. ARDS developed less frequently in the study group, but there was no significant difference in the incidence of AKI, AHF and infectious complications between the groups.

Intelligent berberine-loaded erythrocytes attenuated inflammatory cytokine productions in macrophages

Erythrocytes are impressive tools for drug delivery, especially to macrophages. Therefore, berberine was loaded into erythrocytes using both hypotonic pre-swelling and endocytosis methods to target macrophages. Physicochemical and kinetic parameters of the resulting carrier cells, such as drug loading/release kinetics, osmotic fragility, and hematological indices, were determined. Drug loading was optimized for the study using Taguchi experimental design and lab experiments. Loaded erythrocytes were targeted to macrophages using ZnCl2 and bis-sulfosuccinimidyl-suberate, and targeting was evaluated using flow cytometry and Wright–Giemsa staining. Differentiated macrophages were stimulated with lipopolysaccharide, and the inflammatory profiles of macrophages were evaluated using ELISA, western blotting, and real-time PCR. Findings indicated that the endocytosis method is preferred due to its low impact on the erythrocyte’s structural integrity. Maximum loading achieved (1386.68 ± 22.43 μg/ml) at 1500 μg/ml berberine treatment at 37 °C for 2 h. Berberine successfully inhibited NF-κB translation in macrophages, and inflammatory response markers such as IL-1β, IL-8, IL-23, and TNF-α were decreased by approximately ninefold, sixfold, twofold, eightfold, and twofold, respectively, compared to the LPS-treated macrophages. It was concluded that berberine-loaded erythrocytes can effectively target macrophages and modulate the inflammatory response.

The value of lung function assessment and Testin expression detection in clinicopathological features and prognosis of NSCLC patients.

The aim of this study is to investigate the clinical value and potential prognostic significance of lung function assessment and Testin expression in non-small cell lung cancer (NSCLC) patients. The NSCLC patients were classified into three groups according to lung function: group of normal lung function, group of PRISm (preserved ratio impaired spirometry) (FEV1, forced expiratory volume during the first second < 80% predicted and FEV1/FVC (forced vital capacity) ≥ 70%) and group of COPD (chronic obstructive pulmonary disease) (FEV1/FVC < 70%). The pre-operational clinicopathological characteristics of these patients were recorded and the markers of systemic inflammatory response, including neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) and eosinophils (EOS), were compared between three groups. The expression of Testin in NSCLC samples was detected by IHC and we further explored the correlation between Testin expression and clinicopathological characteristics and prognosis of NSCLC patients. Finally, Cox regression analysis was conducted to study the prognostic factors of NSCLC patients. Of the 158 NSCLC patients, percentages of normal lung function, PRISm and COPD were 41.4%, 22.8% and 36.1%, respectively. Patients with tumor in the left lung were more likely to have pulmonary dysfunction (PRISm and COPD) than the right lung. The markers of systemic inflammatory response showed differences to various degree in the three groups and NSCLC patients with PRISm or COPD presented more unfavorable prognosis than patients with normal function. The expression of Testin correlated with lymph node metastasis, TNM stage and tumor invasion of NSCLC patients. Moreover, patients with low Testin expression exhibited poorer disease-free survival and overall survival than those with high Testin expression. In Cox regression analysis, we found that PRISm, COPD and Testin expression served as prognostic factors in NSCLC patients. The presence of COPD or PRISm influenced systemic inflammatory response and prognosis of NSCLC patients. Testin expression correlated with clinicopathological features and could be potentially used as a prognostic marker in NSCLC.

Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats

Pirfenidone (PFD), one acceptable medication for treating idiopathic pulmonary fibrosis (IPF), is not well tolerated by patients at full doses. Hence, employing of some approaches such as combination therapy may be applicable for increasing therapeutic efficacy of PFD. Losartan (LOS), an angiotensin II receptor antagonist, could be a suitable candidate for combination therapy because of its stabilizing effect on the pulmonary function of IPF patients. Therefore, this study aimed to investigate the effects of LOS in combination with PFD on bleomycin (BLM)-induced lung fibrosis in rats. BLM-exposed rats were treated with LOS alone or in combination with PFD. The edema, pathological changes, level of transforming growth factor-β (TGF-β1), collagen content, and oxidative stress parameters were assessed in the lung tissues. Following BLM exposure, the inflammatory response, collagen levels, and antioxidant markers in rat lung tissues were significantly improved by PFD, and these effects were improved by combination with LOS. The findings of this in vivo study suggest that the combined administration of PFD and LOS may provide more potent protection against IPF than single therapy through boosting its anti-inflammatory, anti-fibrotic, and anti-oxidant effects. These results hold promise in developing a more effective therapeutic strategy for treating of lung fibrosis.

The potential molecular markers of inflammatory response in KOA with AD based on single-cell transcriptome sequencing analysis and identification of ligands by virtual screening.

Alzheimer's disease (AD) and osteoarthritis (OA) are both senile degenerative diseases.Clinical studies have found that OA patients have a significantly increased risk of AD in their later life. This study hypothesized that chronic aseptic inflammation might lead to AD in KOA patients. However, current research has not yet clarified the potential mechanism between AD and KOA. Therefore, this study intends to use KOA transcriptional profiling and single-cell sequencing analysis technology to explore the molecular mechanism of KOA affecting AD development, and screen potential molecular biomarkers and drugs for the prediction, diagnosis, and prognosis of AD in KOA patients. It was found that the higher the expression of TXNIP, MMP3, and MMP13, the higher the risk coefficient of AD was. In addition, the AUC of TXNIP, MMP3, and MMP13 were all greater than 0.70, which had good diagnostic significance for AD. Finally, through the virtual screening of core proteins in FDA drugs and molecular dynamics simulation, it was found that compound Cobicistat could be targeted to TXNIP, Itc could be targeted to MMP3, and Isavuconazonium could be targeted to MMP13.To sum up, TXNIP, MMP3, and MMP13 are prospective molecular markers in KOA with AD, which could be used to predict, diagnose, and prognosis.

Microenvironment, systemic inflammatory response and tumor markers considering consensus molecular subtypes of colorectal cancer.

Introduction: Colorectal carcinomas (CRC) are one of the most frequent malignancies worldwide. Based on gene expression profile analysis, CRCs can be classified into four distinct subtypes also known as the consensus molecular subtypes (CMS), which predict biological behaviour. Besides CMS, several other aspects of tumor microenvironment (TME) and systemic inflammatory response (SIR) influence the outcome of CRC patients. TME and inflammation have important role in the immune (CMS1) and mesenchymal (CMS4) subtypes, however, the relationship between these and systemic inflammation has not been assessed yet. Our objective was to evaluate the connection between CMS, TME and SIR, and to analyze the correlation between these markers and routinely used tumor markers, such as CEA (Carcinoembryonic Antigen) and CA19-9 (Carbohydrate Antigen 19-9). Methods: FFPE (Formalin Fixed Paraffin Embedded) samples of 185 CRC patients were collected. TME was described using tumor-stroma ratio (TSR), Klintrup-Makinen (KM) grade, and Glasgow Microenvironment Score (GMS). CMS classification was performed on tissue microarray using MLH1, PMS2, MSH2 and MSH6, and pan-cytokeratin, CDX2, FRMD6, HTR2B and ZEB1 immunohistochemical stains. Pre-operative tumor marker levels and inflammatory markers [C-reactive protein - CRP, albumin, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute platelet count (APC)] and patient history were retrieved using MedSolution database. Results: Amongst TME-markers, TSR correlated most consistently with adverse clinicopathological features (p < 0.001) and overall survival (p < 0.001). Elevated CRP and modified Glasgow Prognostic Score (mGPS) were associated with worse outcome and aggressive phenotype, similarly to tumor markers CEA and CA19-9. Stroma-Tumor Marker score (STM score), a new combined score of CA19-9 and TSR delivered the second best prognostication after mGPS. Furthermore, CMS4 showed association with TSR and several laboratory markers (albumin and platelet derived factors), but not with other SIR descriptors. CMS did not show any association with CEA and CA19-9 tumor markers. Conclusion: More routinely available TME, SIR and tumor markers alone and in combination deliver reliable prognostic data for choosing the patients with higher risk for propagation. CMS4 is linked with high TSR and poor prognosis, but in overall, CMS-classification showed only limited effect on SIR- and tumor-markers.

The effectiveness of a Lactobacillus probiotic on measures of psychosocial health in adults diagnosed with subthreshold depression: a double-blind, randomised, placebo-controlled trial

Depression is the leading cause of disability worldwide(1). The microbiota-gut-brain axis may play a role in the aetiology of depression, and probiotics show promise for improving mood and depressive state(2). Further evidence is required to support mechanisms and in high-risk populations, such as those with sub-threshold depression (which may be 2-3 times more prevalent than diagnosed depression)(3). The aims were to assess the efficacy of a probiotic compared with placebo in reducing the severity of depressive symptoms in participants with subthreshold depression, and to investigate potential mechanistic markers of inflammatory, antioxidant status and stress response. A double-blind, randomised, placebo-controlled trial was conducted in participants meeting diagnosis of subthreshold depression (DSM-5); aged 18-65 years; ≥18.5 kg/m2 body mass index; not taking antidepressants, centrally acting medications, probiotics nor antibiotics for at least 6 weeks. The probiotic (4 × 109 AFU/CFU, 2.5 g freeze-dried powder containing Lactobacillus fermentum LF16 (DSM26956), L. rhamnosus LR06 (DSM21981), L. plantarum LP01 (LMG P-21021), Bifidobacterium longum BL04 (DSM 23233)) or placebo was taken daily for 3-months. Data was collected at 3 study visits (pre-, mid- (6 weeks), post-intervention). Self-reported questionnaires measured psychological symptoms (Beck Depression Inventory, BDI; Hospital Anxiety Depression Scale, HADS) and quality of life. Blood and salivary samples were collected for biomarkers including cortisol awakening response (CAR). General linear models examined within-group and between-group differences across all time points. Thirty-nine participants completed the study (n = 19 probiotic; n = 20 placebo) using intention-to-treat analysis. The probiotic group decreased in BDI score by −6.5 (95% CI −12.3; −0.7) and −7.6 (95% CI −13.4; −1.8) at 6 and 12 weeks, respectively. The HADS-A score decreased in the probiotic group by −2.8 (95% CI −5.2; −0.4) and −2.7 (95% CI −5.1; −0.3) at 6 and 12, respectively. The HADS-D score decreased in the probiotic group by −3.0 (95% CI −5.4; −0.7) and −2.5 (−4.9; −0.2) at 6 and 12 weeks of intervention, respectively. No between group differences were found. There were no changes in perceived stress or quality of life scores. The probiotic group had reduced hs-CRP levels (7286.2 ± 1205.8 ng/dL vs. 5976.4 ± 1408.3; P = 0.003) and increased total glutathione (14.2 ± 8.9 ng/dL vs. 9.3 ± 4.7; P = 0.049) compared to placebo, post intervention. Lower levels of CAR were found in the probiotic compared to placebo (−0.04 ± 0.17 μg/dL vs. 0.16 ± 0.25; P = 0.009). A significant reduction in depressive symptoms and anxiety was observed within the probiotic group only. These results were supported by improvements observed in biomarkers, suggesting probiotics may improve psychological wellbeing in adults experiencing sub-threshold depression, by potential pathways involved in central nervous system homeostasis and inflammation. Future analyses are required to understand changes within the intestinal microbiota and to clarify how their metabolites facilitate emotional processing.

Characteristics Of Pathogenetic Links In Vascular Remodeling And Bone Tissue Destruction In Postmenopausal Women With Arterial Hypertension

Background — Much attention is drawn to the role of the nonspecific immune inflammatory vascular response as a link of general pathogenetic mechanisms with changes in the elastic properties of arteries and the phenomena of destructive changes in bones. Objective — We aimed to study the role of nonspecific immune inflammatory markers, parathyroid hormone and female sex hormones as predictors of cardiovascular and degenerative bone changes in postmenopausal women with arterial hypertension (AH) and osteoporosis (OP). Methods — We examined 104 patients (mean age: 54.03±9.56 years) distributed among three groups: healthy women, females with AH and osteopenia, and women with AH and OP. The markers of immune inflammatory response, endothelial dysfunction, hormonal, mineral, and vitamin statuses were analyzed simultaneously with 24-hour ambulatory monitoring of blood pressure, and parameters of vascular wall stiffness and densitometry to elucidate the predictors of cardiovascular and degenerative bone changes in postmenopausal women. Results — For patients with AH and osteopenia, a significant parameter associated with the risk of OP was pulse wave velocity (PWV); its increase exceeding 12.05 m/s was associated with a 3.8-fold increase in the risk of OP. Levels of proinflammatory indicators, interleukins IL-6 and IL-8, tumor necrosis factor-α, high-sensitivity C-reactive protein, and parathyroid hormone were elevated, while levels of progesterone and IL-10 were decreased. Conclusion — Timely specialized multidirectional research of biochemical and instrumental parameters (PWV and densitometry) could become the basis for the development of a personalized strategy for the prevention and treatment of women in order to avoid dangerous cardiovascular and bone complications.

Monocyte-Mediated Thrombosis Linked to Circulating Tissue Factor and Immune Paralysis in COVID-19.

SARS-CoV-2 infections cause COVID-19 and are associated with inflammation, coagulopathy, and high incidence of thrombosis. Myeloid cells help coordinate the initial immune response in COVID-19. Although we appreciate that myeloid cells lie at the nexus of inflammation and thrombosis, the mechanisms that unite the two in COVID-19 remain largely unknown. In this study, we used systems biology approaches including proteomics, transcriptomics, and mass cytometry to define the circulating proteome and circulating immune cell phenotypes in subjects with COVID-19. In a cohort of subjects with COVID-19 (n=35), circulating markers of inflammation (CCL23 [C-C motif chemokine ligand 23] and IL [interleukin]-6) and vascular dysfunction (ACE2 [angiotensin-converting enzyme 2] and TF [tissue factor]) were elevated in subjects with severe compared with mild COVID-19. Additionally, although the total white blood cell counts were similar between COVID-19 groups, CD14+ (cluster of differentiation) monocytes from subjects with severe COVID-19 expressed more TF. At baseline, transcriptomics demonstrated increased IL-6, CCL3, ACOD1 (aconitate decarboxylase 1), C5AR1 (complement component 5a receptor), C5AR2, and TF in subjects with severe COVID-19 compared with controls. Using stress transcriptomics, we found that circulating immune cells from subjects with severe COVID-19 had evidence of profound immune paralysis with greatly reduced transcriptional activation and release of inflammatory markers in response to TLR (Toll-like receptor) activation. Finally, sera from subjects with severe (but not mild) COVID-19 activated human monocytes and induced TF expression. Taken together, these observations further elucidate the pathological mechanisms that underlie immune dysfunction and coagulation abnormalities in COVID-19, contributing to our growing understanding of SARS-CoV-2 infections that could also be leveraged to develop novel diagnostic and therapeutic strategies.

Application of mesenchymal stem cells in severe acute experimental pancreatitis

Background. The significance of the problem of acute pancreatitis is due to an increase in the incidence with an increase in the number of common forms of pancreatic necrosis, accompanied by a high incidence of severe complications.Aim. To determine the effect of regional application of mesenchymal stromal cells on the systemic manifestations of severe acute experimental pancreatitis.Material and methods. This experimental study was carried out on 42 adults Wistar rats. Acute pancreatitis was induced by administering 0.3 ml of 5% solution of non-ionic polyethylene glycol octylphenol ether detergent into the caudal part of the pancreas. The animals were randomly divided into 4 groups: Group I (n=6) consisting of intact animals, Group II (control group) (n=12) of rats with untreated pancreatitis, Group III (n=12) of rats with pancreatitis treated: anesthesia + infusions of 0.9% sodium chloride solution (saline), and Group IV (n=12) of rats with pancreatitis treated: anesthesia + infusions of saline + regional application of mesenchymal stromal cells. Animals were taken out of the experiment by euthanasia on the 3rd and 7th day. The hematological parameters, markers of systemic manifestation of the pathological process (pancreatic amylase, aspartate aminotransferase, alanine aminotransferase, urea, creatinine), markers of endogenous intoxication (lipid peroxidation activity, nitric oxide level), markers of systemic inflammatory response (C-reactive protein, tumour necrosis factor-alpha, interleukin-6) have been evaluated.Results. The application of mesenchymal stromal cells in the early stages of acute pancreatitis made a favourable effect on the platelet count, the level of glycemia, helped to reduce the content of endogenous intoxication elements (malonic dialdehyde, nitric oxide) and of those of the systemic inflammatory response (interleukin-6, tumor necrosis factor-α, C-reactive protein), which are key links in the pathogenesis of severe acute pancreatitis.Conclusion. Comparison of different treatment regimens for acute experimental pancreatitis has shown that the early use of mesenchymal stromal cells has a systemic positive effect and confirms the therapeutic efficacy of the method in the treatment of this disease.