Systemic Inflammatory Reaction Research Articles

Markers of enterocyte damage, microbial translocation and systemic inflammation following 9 hours of heat exposure in young and older adults.

Heat stress induced damage to the gastrointestinal barrier can induce local and systemic inflammatory reactions implicated in heat-stroke. Gastrointestinal barrier damage has been shown to be greater in older relative to young adults following hyperthermia. However, comparisons between young and older adults have been limited to brief exposures (3-h), which may not reflect the duration of heat stress experienced during heat waves. We therefore evaluated markers of intestinal epithelial damage (Log transformed intestinal fatty acid binding protein, IFABPLOG), microbial translocation (soluble cluster of differentiation 14, sCD14LOG), and systemic inflammation (tumour necrosis factor alpha, TNF-αLOG; interleukin 6, IL-6LOG; C-reactive protein, CRP) in 19 young (interquartile range: 21-27 yr; 10 females) and 37 older (68-73 yr; 10 females) adults before and after 9-h of rest in 40°C (9% relative humidity). The magnitude of the increase in IFABPLOG was 0.38 log pg/mL (95% CI, 0.10, 0.65 log pg/mL) greater in the older relative to young cohort (P=0.049) after 9-h heat exposure. At baseline both IL-6LOG and CRP concentrations were higher in the older (IL-6: 2.67 (1.5) log pg/mL, CRP: 0.28 (1.5) mg/mL) relative to the young (IL-6: 1.59 log pg/mL, SD 1.2; CRP: 0.11 mg/mL, SD 1.7) group (both P<0.001). The change in IL-6 and CRP was similar between groups following 9-h heat exposure (IL-6: P=0.053; CRP: P=0.24). Neither sCD14LOG and TNF-αLOG were different between groups at baseline nor altered after 9-h heat exposure. Our data indicate that age may modify intestinal epithelial injury following 9 h of passive heat exposure.

Clinical, radiological, and laboratory features of HIV-negative pulmonary cryptococcosis with regard to serum lateral flow assay

IntroductionCryptococcosis is the second most common invasive yeast infection in China. Pulmonary cryptococcosis (PC) is difficult to diagnose due to the lack of specific clinical features and the limitation of diagnostic techniques. Although lateral flow assay was very useful in diagnosing cryptococcal infection, quite a few patients with PC presented negative serum lateral flow assay (sLFA).MethodsWe conducted a retrospective study of HIV-negative patients who were diagnosed with PC in our hospital over the past decade to explore the potential relationship between the clinical profiles and sLFA in PC.ResultsIn total, 112 patients with sLFA tested were enrolled in this study, of which 58.93% were male. The positivity rate of sLFA for PC was 91.07%. The extent of pulmonary lesions was positively correlated with sLFA grade (Spearman r = 0.268, p &amp;lt; 0.01). Solitary nodule (SN) and pneumonia were the most common imaging findings in PC with negative and positive sLFA respectively. Among 65 symptomatic PC patients, 14 presented with fever and had higher hypersensitive C-reactive protein (hsCRP) level and more extensive pulmonary involvement (Mann-Whitney U test, p &amp;lt; 0.05) than those without fever. Symptomatic PC patients were more likely to have positive results of sLFA (Mann-Whitney U test, p = 0.05) compared against asymptomatic ones.DiscussionIn conclusion, negative sLFA cannot exclude PC in patients with a solitary nodule in lung. Positive sLFA is more reliable in diagnosing PC in symptomatic patients with diffused lesions in lung who generally experience a more severe systemic inflammatory reaction.

A Th2-type immune response and low-grade systemic inflammatory reaction as potential immunotoxic effects in intensive agriculture farmers exposed to pesticides

Pesticides are chemicals widely used in agriculture to keep crops healthy and prevent them from being destroyed by pests, thus contributing to a sustainable food and feed production. However, long-term exposure to these compounds may be harmful to human health as they can affect the function of various organs systems, including the immune system. There is growing evidence that pesticides may increase the risk of developing immune-based diseases and inflammation. This study assessed whether greenhouse farmers occupationally exposed to pesticides presented alterations in immunoregulatory proteins, used as surrogate biomarkers of immune function. The study population consisted of 175 greenhouse workers occupationally exposed to pesticides and 91 non-exposed controls. Serum levels of 27 cytokines, chemokines and growth factors were measured using a magnetic bead-based immunoassay in a subpopulation of 111 greenhouse workers and 79 non-exposed controls. Since analytical determinations were performed in two periods of the same crop season with different use of pesticides (period of high and low pesticide exposure), linear mixed models for repeated measures were used to optimize statistical inference. The increase in IL-13, IL-4 and IL-6 observed in greenhouse workers compared to controls, and in the period of high exposure to pesticides relative to that of low exposure, suggest an altered Th1/Th2 balance towards the Th2 response. This finding points to a type-2 inflammation commonly presented as allergic inflammation, which has often been reported in farm-workers and in which pesticide exposure is considered a risk factor. Furthermore, the increase in IL-1β and VEGF, mediators of inflammation and angiogenesis, may suggest a low-grade systemic inflammation that might underlie chronic pathological conditions linked to pesticide exposure.

A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel for infected wounds

Bacterial infections during wound healing impede the healing process and trigger local or systemic inflammatory reactions. Consequently, there is an urgent need to develop a new material with antimicrobial and antioxidant properties to promote infected wound healing. A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel (HMn) is prepared by employing MnO2 nanosheets into 4ARM-PEG5000-SH crosslinked methacrylated hyaluronic acid (HAMA) network. The coordination between sulfhydryl groups of 4ARM-PEG5000-SH and MnO2 nanosheets ensures entrapment of the nanosheets within the hydrogel, while the interaction between 4ARM-PEG5000-SH and HAMA results in facile gelation through thiol-ene click reaction. MnO2 nanosheets exhibit strong photothermal properties and reactive oxygen species (ROS) scavenging abilities, while hyaluronic acid promotes wound healing. When subjected to near-infrared (NIR) irradiation, the HMn achieves a bactericidal rate of 95.24 % for Staphylococcus aureus and nearly 100 % for Escherichia coli. In animal experiments, treatment with the HMn under NIR irradiation results in the best wound healing outcomes. Both in vitro and vivo biocompatible assays demonstrate that the HMn has rarely cell cytotoxicity and tissue damage. The HMn is easy to prepare and has good biocompatibility as well as efficient antibacterial and antioxidant properties, providing a novel method for the treatment of infected wounds.

Aspects of pharmacotherapy with steroids in SARS-CoV-2 infection (literature review)

In recent years, the SARS-CoV-2 pandemic has posed a significant challenge to global public health. Furthermore, infection with SARS-CoV-2 can result in acute respiratory distress syndrome due to excessive systemic inflammation, leading to multiple organ failure and eventual death. Furthermore, the challenge of reducing excessive systemic inflammation, specifically by decreasing the production of pro-inflammatory cytokines in response to SARS-CoV-2, remains unresolved. The use of glucocorticosteroids for SARS-CoV-2 infection remains controversial. Further research is required to support the routine use of steroids in intensive care protocols for SARS-CoV-2, as the current basis is insufficient. This review provides an analysis of literary sources, guidelines, and modern international recommendations on pathogenetic therapy of SARS-CoV-2 to prevent and eliminate hyperproduction of pro-inflammatory cytokines using glucocorticosteroid agents. The aim of this work is to analyse contemporary literary sources on the clinical and pharmacological justification for the use of glucocorticosteroids in clinical practice for SARS-CoV-2 infection. The scientific literature analysis indicates that glucocorticosteroid therapy cannot be recommended for routine use in therapeutic practice for patients with SARS-CoV-2 infection. Thus, with a mild course of SARS-CoV-2 infection, when the patient does not need oxygen support, glucocorticosteroids are contraindicated. Whereas in severe course, in acute respiratory distress syndrome with severe respiratory failure, their use is absolutely necessary, and they are recommended for mandatory use. There is a need for a generalised definition of the optimal glucocorticosteroid agent, including indications, dosage, and duration of use in SARS-CoV-2 infection therapy programs. Keywords: systemic inflammatory reaction, proinflammatory cytokines, hypothalamic-pituitary-adrenal system, glucocorticosteroids.

Abstract 6884: Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract cancer

Abstract Background: The tumor microenvironment (TME) is composed of not only cancer cells but also an extracellular matrix and many types of non-cancerous cells, including fibroblasts and immune cells. In recent years, infiltrating immune cells in TME are known as a predictor of chemotherapy and immunotherapy effectiveness. The purpose of this study is to evaluate infiltrations of lymphocytes and macrophages in biliary tract cancers (BTCs). Methods: Clinical data and tissues were obtained from 130 patients who underwent surgical treatment for BTCs (intrahepatic, perihilar, and distal bile duct cancer, gallbladder cancer, and ampullary cancer) at our institution between 2001 and 2017.The immunohistochemical evaluation was performed to evaluate the number of CD8+ T cells, CD4+ T cells and FOXP3+ T cells and CD68+ Macrophages around the tumor cells. We defined Immunoscore based on the status of infiltrating immune cells. With CD8-high, CD4-high, and FOXP3-high TILs and CD68-low TAMs as one factor, the number of factors was counted in each case, and Immunoscore was assigned a score of 5 stages, from 0 to 4. It was high for the score of 3-4 and low for the score of 0-2. Also, to evaluate the correlation with TME and systemic inflammatory reaction, we examined blood inflammatory biomarker from peripheral blood samples. Results: A total of 59 cases had high Immunoscore and 71 cases had low Immunoscore. Patients with high Immunoscore showed significantly superior overall survival (OS) and recurrence free survival (RFS) than those with low Immunoscore (median OS 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p &amp;lt; 0.001). For OS, low Immunoscore, positive lymph node metastasis, presence of distant metastasis, and high serum CA19-9 level were independent poor prognostic factors (hazards ratio 2.05, 3.48, 1.7, and 2.05; p = 0.01, p = 0.005, p = 0.05, and p = 0.01, respectively). For RFS, low Immunoscore, T classification of pT3-4, and presence of distant metastasis were independent poor prognostic factors with hazards ratio of 2.41 (p = 0.001), 2.16 (p = 0.005), and 3.58 (p = 0.005), respectively. Patients with high preoperative Neutrophil-to-lymphocyte ratio (NLR) had a significantly lower average number of CD8+ T cells as compared to patients with low NLR (p = 0.02). Preoperative NLR was associated with infiltrating CD8+ T cells in TME. Conclusions: High Immunoscore group had significantly longer OS and RFS and was an independent good prognostic factor. Also, infiltrating CD8+ T cells in TME correlated preoperative NLR. Our findings indicated that in biliary tract cancer, the evaluation of infiltrating immune cells in TME was useful to predict patient prognosis, and preoperative NLR may predict the tumor infiltrating CD8+ T cells. Citation Format: Kousuke Hatta, Ryota Tanaka, Kenjiro Kimura, Shinpei Eguchi, Go Ohira, Hiroji Shinkawa, Kohei Nishio, Masahiko Kinoshita, Shigeaki Kurihara, Shuhei Kushiyama, Takahito Kawaguchi, Naoki Tani, Koichi Nakanishi, Mizuki Yoshida, Takeaki Ishizawa. Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6884.

Protective role of forsythoside B in Kawasaki disease-induced cardiac injury: Inhibition of pyroptosis via the SIRT1–NF-κB–p65 signaling pathway

Kawasaki disease (KD), an acute exanthematous febrile pediatric illness involving systemic non-specific inflammatory reactions in small- and medium-sized arteries, poses a significant risk of coronary artery and myocardial inflammatory injury. Developing new KD treatments with improved safety and fewer side-effects is highly desirable. Forsythoside B (FTS-B), extracted from the Forsythia suspensa plant, exerts anti-inflammatory activity by inhibiting NF-κB, which is regulated by SIRT1, the reduced expression of which is strongly associated with cardiovascular disease. However, it has yet to be established whether FTS-B influences KD-related inflammatory damage. In this study, we investigated the effects of FTS-B on inflammation in cellular and murine models of KD. Our findings revealed that KD is associated with cardiac dysfunction and inflammatory injury to myocardial and human coronary artery endothelial cells (HCAECs), resulting in a pyroptosis-feedback loop. Both cellular and KD models were characterized by reduced SIRT1 expression and increased NF-κB p65 expression. Contrastingly, the rates of pyroptosis in both murine model myocardial tissues and HCAECs were significantly alleviated in response to FTS-B treatment. Also in both models, we detected an increase of SIRT1 expression and a decrease in the expression of p65. Further examination of the protective mechanism of FTS-B using the SIRT1-specific inhibitor, EX 527, revealed that this inhibitor blocked the palliative effects of FTS-B on inflammatory injury-induced pyroptosis. These results highlight the potential utility of the SIRT1–NF-κB–p65 pathway as a therapeutic target for KD treatment and demonstrate that FTS-B can alleviate KD-induced cardiac and HCAEC inflammatory injury via inhibition of pyroptosis.

Expression of Siglec-9 in peripheral blood neutrophils was increased and associated with disease severity in patients with AECOPD

BackgroundThe pathogenesis and treatment strategies for chronic obstructive pulmonary disease (COPD) require further exploration. Abnormal neutrophil inflammation and the overexpression of neutrophil extracellular traps (NETs) are closely associated with acute exacerbations of COPD (AECOPD). Siglec-9, a specific receptor expressed on neutrophils that inhibits their function, prompted us to investigate its relationship with NETs found in induced sputum and the severity of the disease. MethodsWe collected clinical data from patients with AECOPD and assessed the expression of Siglec-9 in peripheral blood neutrophils and the presence of NETs in induced sputum. We then observed the correlation between Siglec-9, the inflammatory response, and the severity of AECOPD. ResultsWe observed an increase in the expression of Siglec-9 in the peripheral blood neutrophils of patients with AECOPD. Concurrently, these patients exhibited more severe clinical symptoms, higher systemic inflammation levels, and a reduced quality of life compared to those with induced sputum NET expression. Further subgroup analysis of AECOPD patients with high Siglec-9 expression revealed worsened quality of life and more severe inflammation, particularly in indicators such as the BODE index, CRP, peripheral blood neutrophil count, IL-6, IL-8, TNF-α expression, and others. Furthermore, we noted a significant increase in NET-specific expression in the sputum of patients with high Siglec-9 expression levels. In comparison to patients with low Siglec-9 expression, those with high expression experienced more systemic inflammatory reactions and a lower quality of life. Correlation analysis of the aforementioned indicators revealed that the expression ratio of Siglec-9 in the peripheral blood of patients correlated with lung function, quality of life, and NETs in the induced sputum of patients with AECOPD. ConclusionThe increased expression of Siglec-9 in peripheral blood neutrophils of AECOPD patients leads to elevated NET expression in induced sputum, exacerbating the systemic inflammatory response and worsening lung function and quality of life in these patients.

The shrapnel-crushed wounds in dogs: status evaluation and therapy for wound healing

Determining the clinical and laboratory status of animals with crushed wounds as a result of the traumatic effect of ammunition fragments, as well as the wound healing effect of ecologically safe drugs based on natural beekeeping products is of great importance under the conditions of the animals' stay in the war zone and territories subject to rocket-bomb and artillery fire. The aim of the research is to study the clinical condition of dogs with shrapnel-crushed wounds, observing its dynamics during systemic therapy and evaluating the therapeutic effect of wound healing using the universal biological ointment Unibiol®. During the research, various physical, hematological, biochemical, hemorheological, hemodynamic, and statistical methods were employed. Six animals with shrapnel-crushed wounds on their limbs and groin were analyzed. It was established that due to the traumatic factor, injuries in dogs are characterized by extensive tissue destruction and deconstruction. The overall condition of the animals, based on clinical signs, is described as toxemic-septic. Hematological changes such as anemia, leukocytosis, thrombocytopenia, left shift in the nucleus, monocytosis, and lymphocytosis indicate a systemic inflammatory reaction and a septic state in the dogs' bodies. Biochemical studies revealed hypoalbuminemia leading to hypoproteinemia, creatinine elevation, uremia, elevated levels of indicator transaminases, suggesting multi-organ failure. A significant decrease in circulating blood volume, increased spontaneous platelet aggregation, characterizes a moderate traumatic circulatory shock, while a 5-fold increase in the circulation of D-dimer levels indicates a significant potential for disseminated intravascular coagulation syndrome. Following infusion and antibiotic therapy, wound sanitation over 5 days led to a significant restoration of the clinical-laboratory status of the injured dogs, setting the stage for Unibiol® ointment wound-healing therapy. As a result of the treatment conducted over 21 days, the wound defect healed with the formation of complete granulation tissue and an elastic scar. The clinical trials conducted allow recommending Unibiol® ointment for effective and environmentally safe healing of severe shrapnel-crushed wounds.

Mapping the Landscape of Obesity Effects on Male Reproductive Function: A Bibliometric Study.

Due to changes in lifestyle and dietary habits, the global population with obesity is increasing gradually, resulting in a significant rise in the number of individuals having obesity. Obesity is caused by an imbalance between energy intake and consumption, leading to excessive fat accumulation, which interferes with normal human metabolism. It is also associated with cardiovascular disease, metabolic syndrome, male reproductive endocrine regulation disorders, systemic and local inflammatory reactions, excessive oxidative stress, and apoptosis. All these factors can damage the internal environment for sperm generation and maturation, resulting in male sexual dysfunction, a decline in sperm quality, and lower fertility. This study analyzes the trends and priorities of the effects of obesity on male reproductive disorders from a bibliometric perspective. This study uses the Web of Science as the statistical source, covering all time spans. Tools like Web of Science, VOSviewer, and CiteSpace are used to analyze countries, institutions, authors, journals, and keywords in the field. Total publications, total citations, and average number of citations are selected for statistics. The results show that the research on the impact of obesity on male reproductive function can be roughly divided into three stages: the initial stage, the slow development stage, and the rapid development stage. Our statistical scope includes 463 highly relevant articles that we have screened. We found that the journal with the most publications in this field is Andrologia, and the institution with the highest total citations is the University of Utah. The most influential countries, institutions, and authors in this field are the United States, the University of Utah, and Carrell, Douglas. Currently, research related to the impact of obesity on male reproduction focuses mainly on three aspects: biochemistry, molecular biology, and reproductive biology. The keyword explosion results indicate that sperm, obesity, and male reproduction are at the forefront and trends of future research in this field. There has been a shift from basic biochemical and molecular research to research on molecular mechanisms relying on omics technologies. However, we have observed that the number of papers published in 2022 is lower than in 2021, indicating a growth interruption during this period. Considering that this deviation may be due to the impact of the COVID-19 pandemic, it may hinder the progress of certain experiments in 2022. In recent years, China has rapidly developed research in this field. However, the average citation rate is relatively low, indicating the need for Chinese scholars to improve the quality of their articles further. Based on our research and in the context of global obesity, men are at risk of increased infertility. Addressing this issue relies on our continued research into the mechanisms of obesity-related male reproductive disorders. Over the past forty-three years, with the contributions of scientists worldwide, research in this field has flourished. The impact of obesity on male reproductive disorders has been extensively studied. Currently, research in this field primarily focuses on male sperm function, sperm quality, and the effects or mechanisms of cells on male reproduction. Future trends in this field should concentrate on the relationship between male fertility and energy metabolism, as well as the endocrine function of adipose tissue. This study comprehensively analyzes the current research status and global trends in obesity and male reproductive disorders. We also discuss the future developments in this field, making it easier for researchers to understand its developmental history, current status, and trends, providing valuable reference for effective exploration in this area.

Hypertonic saline inhalation therapy among patients with moderate asthma and functional dyspepsia commorbidity

Aim: Dry powder hypertonic saline inhalation use possibilities evaluation in moderate asthma and functional dyspepsia patients. Materials and Methods: 68 moderate asthma and functional dyspepsia patients were examined and treated according to the standard protocols, serum and erythrocytes membrane fatty acid levels were evaluated. The groups of patients with (n=35) and without (n=33) additional dry powder hypertonic saline inhalation use were compared after 1 month. Results: After additional use of dry powder hypertonic saline inhalations vs only standard treatment the rate of well controlled asthma was 3 fold higher with significantly higher FEV1. We also observed positive dynamics of serum arachidonic and docosahexaenoic acids levels indicating resolution of inflammatory reaction with erythrocytes membranes linoleic acid level normalization (source of antiinflammatory cytokines synthesis) among patients with dry powder hypertonic saline inhalation use vs without it. Among patients who used only standard therapy compared to the control group, the erythrocytes membrane linoleic acid level remained decreased with high serum arachidonic and docosahexaenoic acids levels. Follow-up results (after 1 year) showed a significant decrease in exacerbations frequency among patients who underwent dry powder hypertonic saline inhalation vs only the standard treatment. Conclusions: Among moderate asthma patients with functional dyspepsia use of dry powder hypertonic saline inhalation therapy additionally to the standard treatment allows to improve not only clinical and functional parameters but serum and erythrocytes membranes fatty acids spectrum as well leading to the systemic inflammatory reaction reduction and exacerbations prevention in remote period.

Coronavirus infection and systemic inflammatory reaction syndrome.

Aim: The purpose of this study was a clinical approbation of the Kometad drug (international non-proprietary name sodium colistimethate), an antibiotic from the polymyxin group in patients with severe course of confirmed сoronavirus infection in the intensive care unit of the Branch of the I. Zhekenova Municipal Clinical Infectious Diseases Hospital.. Materials and Methods: The methodology is based on both theoretical and empirical methods of scientific cognition. During the study, the features of the Coronavirus infection and the inflammatory reaction syndrome were considered, which became quite a big problem during the pandemic. Results: The main indications for the tested drug and the consequences of its use for one age group were also determined. Conclusions: The conclusion was made about the positive dynamics of the patients' health status, and recommendations were given for further research in this area. The practical significance of this study lies in the first clinical approbation of the Kometad drug, which can be used in medicine to reduce the severity of the systemic inflammatory reaction syndrome and improve the patient's health as a result of the disease of Coronavirus infection, after further clinical trials of the drug with different age groups of patients.

Investigation of the Effects of Boric Acid Used in the Treatment of Rat Models with Knee Osteoarthritis Induced by Monosodium Iodoacetate on Liver Tissue

Osteoarthritis (OA) is a significant joint disease that can affect the health of individuals in many sectors. Although OA is primarily known as a joint disease in the field of health, it can also cause damage to organs such as the liver due to the systemic inflammatory reactions (SIRS) it triggers. Boric acid (BA), which has been the subject of many studies and has been shown to have anti-inflammatory, anti-apoptotic, antimicrobial, and anticancer properties, is widely used in various areas of the healthcare sector. In this study conducted for this purpose, the protective effect of BA against liver damage caused by OA was investigated. A total of 28 rats were divided into four groups, each consisting of 7 rats. Except for the control group, all animals were induced with monosodium iodoacetate (MIA) to develop OA, and then rats were administered doses of BA ranging 4 and 10 mg/kg for 21 days. In histopathological examinations, severe hepatitis and degenerative changes were observed in the liver tissue of the OA-induced group, while it was found that BA application reduced these damages dose-dependently. Similarly, in immunohistochemical analyses, it was observed that OA induction significantly increased the expression levels of TNF-α, IL-1β, iNOS, and MMP-13 in the liver, but in the groups treated with BA, this expression level significantly decreased depending on the dose. This study observed that BA exhibited anti-inflammatory properties and had a protective effect on liver tissue against SIRS caused by OA.

Exploring the effect and mechanism of cucurbitacin B on cholestatic liver injury based on network pharmacology and experimental verification

Ethnopharmacological relevanceCholestatic liver injury (CLI) is a pathologic process with the impairment of liver and bile secretion and excretion, resulting in an excessive accumulation of bile acids within the liver, which leads to damage to both bile ducts and hepatocytes. This process is often accompanied by inflammation. Cucumis melo L is a folk traditional herb for the treatment of cholestasis. Cucurbitacin B (CuB), an important active ingredient in Cucumis melo L, has significant anti-inflamamatory effects and plays an important role in diseases such as neuroinflammation, skin inflammation, and chronic hepatitis. Though numerous studies have confirmed the significant therapeutic effect of CuB on liver diseases, the impact of CuB on CLI remains uncertain. Consequently, the objective of this investigation is to elucidate the therapeutic properties and potential molecular mechanisms underlying the effects of CuB on CLI. Aim of the studyThe aim of this paper was to investigate the potential protective mechanism of CuB against CLI. MethodsFirst, the corresponding targets of CuB were obtained through the SwissTargetPrediction and SuperPre online platforms. Second, the DisGeNET database, GeneCards database, and OMIM database were utilized to screen therapeutic targets for CLI. Then, protein-protein interaction (PPI) was determined using the STRING 11.5 data platform. Next, the OmicShare platform was employed for the purpose of visualizing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The molecular docking technique was then utilized to evaluate the binding affinity existing between potential targets and CuB. Subsequently, the impacts of CuB on the LO2 cell injury model induced by Lithocholic acid (LCA) and the CLI model induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) were determined by evaluating inflammation in both in vivo and in vitro settings. The potential molecular mechanism was explored by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) techniques. ResultsA total of 122 CuB targets were collected and high affinity targets were identified through the PPI network, namely TLR4, STAT3, HIF1A, and NFKB1. GO and KEGG analyses indicated that the treatment of CLI with CuB chiefly involved the inflammatory pathway. In vitro study results showed that CuB alleviated LCA-induced LO2 cell damage. Meanwhile, CuB reduced elevated AST and ALT levels and the release of inflammatory factors in LO2 cells induced by LCA. In vivo study results showed that CuB could alleviate DDC-induced pathological changes in mouse liver, inhibit the activity of serum transaminase, and suppress the liver and systemic inflammatory reaction of mice. Mechanically, CuB downregulated the IL-6, STAT3, and HIF-1α expression and inhibited STAT3 phosphorylation. ConclusionBy combining network pharmacology with in vivo and in vitro experiments, the results of this study suggested that CuB prevented the inflammatory response by inhibiting the IL-6/STAT3/HIF-1α signaling pathway, thereby demonstrating potential protective and therapeutic effects on CLI. These results establish a scientific foundation for the exploration and utilization of natural medicines for CLI.

Evaluation of the effectiveness of detoxification in the immunorehabilitation of cancer patients

Purpose. Evaluation of the effectiveness of detoxification using enterosorbents in the immunorehabilitation of cancer patients.&#x0D; Materials and methods. 87 patients with metastatic forms of solid tumors of various localizations with metastatic lesions were examined. The patients were divided into 2 groups: study group (41 patients who received detoxification therapy in addition to standard therapy) and comparison group (46 patients who received only standard therapy). The effectiveness of therapy with these drugs was evaluated after one month by assessing clinical and immunological parameters. The assessment of the state of cellular immunity was carried out by flow cytometry.&#x0D; Results. Disturbances in the function of the immune system in the form of insufficiency of the cellular effector link of immunity were detected in all examined patients before the start of therapy. The state of the cellular link of immunity was characterized by an increase in the number of transitional and non-classical subsets of monocytes, an increase in the content of T-, B- and NKT-cells, but with a decrease in NK-cells. An increase in the ratio between the number of T-helpers (CD3+CD4+) and the number of cytotoxic T-cells (CD3+CD8+) was observed in the examined patients. Restoration of cell subsets to the level of control values was found in the examined patients after detoxification therapy as part of immunorehabilitation measures. Significant changes in the number of cells in the blood were absent in the comparison group after the therapy which indicated the absence of a complete relief of the systemic inflammatory response.&#x0D; Conclusion. Chronic toxicosis with the development of a systemic inflammatory reaction on the background of the immune system dysfunctions were found in cancer patients. The use of enterosorbents in complex immunorehabilitation therapy is substantiated and confirmed by the relief of asthenovegetative and dyspeptic syndromes, normalization of the immune system which makes it possible to recommend detoxification therapy during immunorehabilitation measures.

P-suPAR may reflect the inflammatory response after pancreatic surgery

BackgroundSeveral different scoring systems have been developed to predict post-pancreatectomy complications. Currently used inflammatory markers are of only limited value in predicting complications after pancreatic surgery. Plasma soluble urokinase plasminogen activator receptor (P-suPAR) is a prognostic biomarker associated with different inflammatory conditions. The aim of this study was to investigate P-suPAR levels before and after pancreatic surgery. MethodsOne hundred and seventy-six patients evaluated for pancreatic surgery due to suspected malignant or premalignant lesion were recruited for this study at Tampere University Hospital between 2016 and 2021. P-suPAR was analyzed before the planned operation and on postoperative days (PODs) one and three. ResultsOne hundred and thirty-three patients [median age 67 (range 33–84) years, 50 % male] underwent a pancreatic surgery procedure. Compared to preoperative values [median 3.7 (IQR 3.1–4.7) ng/mL], P-suPAR was significantly lower on PODs 1 [3.2 (2.5–3.9) ng/mL; p < 0.001] and 3 [3.2 (2.7–4.1) ng/mL; p < 0.001]. P-suPAR on POD 1 was significantly lower in patients with postoperative pancreatic fistula (POPF) [2.6 (2.1–3.4) ng/mL] than in patients with no POPF [3.2 (2.6–3.8) ng/mL; p = 0.007]. Similar decreases in P-suPAR values were seen in patients with postoperative acute pancreatitis (POAP) and surgical site infection (SSI). ConclusionsAfter pancreatic surgery, P-suPAR level on POD 1 is significantly lower in patients with POPF, POAP or SSI. P-suPAR is decreased after pancreatic resection in all patients. This type of postoperative P-suPAR profile has not previously been described, and may reflect the compensatory anti-inflammatory reaction following the initial systemic inflammatory reaction caused by surgical trauma.

Novel Substituted Azoloazines with Anticoagulant Activity

Hypercytokinemia, or cytokine storm, often complicates the treatment of viral and bacterial infections, including COVID-19, leading to the risk of thrombosis. However, the use of currently available direct anticoagulants for the treatment of COVID-19 patients is limited due to safety reasons. Therefore, the development of new anticoagulants remains an urgent task for organic and medicinal chemistry. At the same time, new drugs that combine anticoagulant properties with antiviral or antidiabetic activity could be helpfull in the treatment of COVID-19 patients, especially those suffering from such concomitant diseases as arterial hypertension or diabetes. We have synthesized a number of novel substituted azoloazines, some of which have previously been identified as compounds with pronounced antiviral, antibacterial, antidiabetic, antiaggregant, and anticoagulant activity. Two compounds from the family of 1,2,4-triazolo[1,5-a]pyrimidines have demonstrated anticoagulant activity at a level exceeding or at least comparable with that of dabigatran etexilate as the reference compound. 7,5-Di(2-thienyl)-4,5-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine has shown the highest ability to prolong the thrombin time, surpassing this reference drug by 2.2 times. This compound has also exhibited anticoagulant activity associated with the inhibition of thrombin (factor IIa). Moreover, the anticoagulant effect of this substance becomes enhanced under the conditions of a systemic inflammatory reaction.

Gebeliğin birinci trimesterinde sistemik inflamatuar belirteçler ile yüksek uterin arter pulsatilite indeksi ilişkisi

Introduction: Preeclampsia is a serious complication of pregnancy leading to maternal and perinatal morbidity and mortality. The etiopathogenesis still remains unsolved, however, various theories currently become well-proved. The leading etiopathogenetic mechanisms are impaired placentation, and placental hypoxia, immune mechanisms, systemic inflammatory reaction, endothelial damage and maternal cardiovascular maladaptation. These mechanisms overlap and induce each other. There are some preventive interventions only if the patients at high-risk are identified timely. This study aimed to investigate the relationship between the inflammatory pathway and placental insufficiency in the first trimester, utilizing the clinical markers of both. It also aims to find out a cheap and easy test to identify those who absolutely need to undergo a comprehensive risk assessment. Methods: This retrospective observational study included 28 patients with high uterine artery resistance (pulsatility index &amp;gt;90th centile) in the first trimester as study group and 67 patients with normal uterine artery resistance in the first trimester as control group. The two groups were compared in terms of risk factors for preeclampsia. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio as systemic inflammatory markers were compared between the groups. ROC analysis was performed to obtain a cut-off value for predicting high uterine artery pulsatility index. Results: Demographic data, anamnestic and examination risk factors for preeclampsia did not differ between the groups. However, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were significantly higher in the patients with uterine artery pulsatility index above 90th centile. A cut off value of 3.58 and 136.9 of Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, respectively were determined for predicting first trimester uterine artery pulsatility index above 90th centile. Conclusions: Neutrophil/lymphocyte and platelet/lymphocyte ratio can simply be used to identify the patients who need referral for uterine artery doppler assessment. Keywords: preeclampsia, uterine artery, pulsatil flow, neutrophil, lymphocyte, placenta

Analysis of Differences in FIB, D-D, and Inflammatory Factor Levels between Patients Undergoing Pelvic Fracture Surgery through the Pararectus Abdominis Approach and Traditional Ilioinguinal Approach

Background: Pelvic fractures require surgery to restore pelvic stability and ensure the restoration of normal physiological structure and function. In pelvic fracture surgery, the choice of surgical approach may have a significant impact on the postoperative recovery and prognosis of patients. This study compared the postoperative recovery effect, coagulation function, and inflammatory indicators of patients through two different surgical approaches: the pararectus abdominis approach and the traditional ilioinguinal approach, aiming to provide more evidence and guidance for clinical practice. Objectives: To observe the differences in fibrinogen (FIB), D-dimer (D-D), and inflammatory factor levels between patients undergoing pelvic fracture surgery through the Pararectus abdominis approach and traditional ilioinguinal approach. Methods: A total of 86 patients with pelvic fractures were divided into a control group (n=43) and an observation group (n=43). The control group received traditional ilioinguinal approach surgery, while the observation group underwent surgery through the Pararectus abdominis approach. Comparisons were between the two groups for the postoperative coagulation function level, inflammatory factor level, and postoperative hip joint function scores. Results: Before surgery, there was no difference in FIB and D-D levels between the two groups (P&gt;0.05). At 3 days and 7 days after the surgery, the levels of FIB and D-D in the two groups increased compared to before the surgery; however, the observation group was lower in this regard than the control group at the same time (P&lt;0.05). The results of the repeated analysis of variance showed that there were group, time, and interaction effects between the two groups (P&lt;0.05). One week after the operation, the scores of hip joint function were compared between the two groups (P&gt;0.05). The hip joint function scores of the two groups were higher at 1 month and 3 months postoperatively than at 1 week, and the observation group was higher than the control group at the same time. Conclusion: Compared with traditional ilioinguinal approach surgery, surgery through the Pararectus abdominis approach can reduce surgical stimulation, decrease coagulation factor secretion, and alleviate systemic inflammatory reactions after the surgery, promoting the recovery of hip joint function.

Melatonin attenuates chronic intermittent hypoxia-induced intestinal barrier dysfunction in mice

Background and purposeChronic intermittent hypoxia (CIH) triggers subclinical intestinal barrier disruption prior to systemic low-grade inflammation. Increasing evidence suggests therapeutic effects of melatonin on systemic inflammation and gut microbiota remodelling. However, whether and how melatonin alleviates CIH-induced intestinal barrier dysfunction remains unclear. Experimental approachC57BL/6 J mice and Caco-2 cell line were treated. We evaluated gut barrier function spectrophotometrically using fluorescein isothiocyanate (FITC)-labelled dextran. Immunohistochemical and immunofluorescent staining were used to detect morphological changes in the mechanical barrier. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) revealed the expression of tight junctions, signal transducer and activator of transcription 3 (STAT3) levels. 16 S rRNA analysis of the colonic contents microflora. Flow cytometry was used to detect cytokines and Th17 cells with and without melatonin supplementation. Key resultsWe found that CIH could induce colonic mucosal injury, including reduction in the number of goblet cells and decrease the expression of intestinal tight junction proteins. CIH could decrease the abundance of the beneficial genera Clostridium, Akkermansia, and Bacteroides, while increasing the abundance of the pathogenic genera Desulfovibrio and Bifidobacterium. Finally, CIH facilitated Th17 differentiation via the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in vitro and elevated the circulating pro-inflammatory cytokine in vivo. Melatonin supplementation ameliorated CIH-induced intestinal mucosal injury, gut microbiota dysbiosis, enteric Th17 polarization, and systemic low-grade inflammation reactions mentioned-above. Conclusion and implicationsMelatonin attenuated CIH-induced intestinal barrier dysfunction by regulating gut flora dysbiosis, mucosal epithelium integrity, and Th17 polarization via STAT3 signalling.