Inflammation-related Indicators Research Articles

Association between inflammation-related indicators and vertebral fracture in older adults in the United States: A cross-sectional study based on National Health and Nutrition Examination Survey 2013-2014.

This study was to examine the association between inflammation-related indexes SII (systemic immune-inflammation index), NLR (neutrophil-to-lymphocyte ratio), PPN (product of platelet count and neutrophil count), and PLR (platelet-to-lymphocyte ratio), and the occurrence of vertebral fractures in older Americans. Patients ⩾60 years of age from the 2013-2014 NHANES database were selected for this study. Restricted cubic spline models and weighted logistic regression models were used to assess the association between inflammation-related indexes and the occurrence of vertebral fractures in older Americans. The predictive value of the inflammation-related indexes on the occurrence of vertebral fractures was assessed using receiver operating characteristic curves (ROC). To examine the robustness of the main findings, a sensitivity analysis was conducted. A total of 1281 patients were included in the analysis, of whole 120 suffered vertebral fractures. Fully adjusted logistic regression showed a significant linear relationship between NLR and the occurrence of vertebral fracture in older Americans (p < .05), but no relationship was found between SII, PLR, and the occurrence of vertebral fracture in older Americans. Meanwhile, NLR was slightly better than other indicators in predicting vertebral fracture. This study found that NLR, as a novel inflammatory marker, can predict the risk of vertebral fracture in older Americans, which is of clinical significance for the prevention and treatment of vertebral fracture in older adults.

Guanxinning for Residual Inflammation of Stable Coronary Artery Disease: A Pilot Randomized Controlled Trial.

Despite statins and other medications central to atherosclerotic cardiovascular disease (ASCVD) secondary prevention, stable coronary artery disease (SCAD) patients remain at significant cardiovascular risk, partly due to residual inflammation risk (RIR). This study aims to assess if adding Guanxinning to standard ASCVD therapy further mitigates RIR in SCAD patients. In a prospective, randomized, single-blind endpoint design, 50 patients with SCAD who received ASCVD standardized treatment strategy were randomly assigned to either take Guanxinning tablets (4 tablets, thrice daily) or no Guanxinning tablets and were followed up for an average of 12weeks. The primary outcomes were changes in inflammation-related indicators, including interleukin-2 (IL-2), IL-4, IL-6, tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP). Compared with the control group, the intervention group showed significantly greater decreases in the levels of IL-2, IL-6, TNF-α, and hs-CRP (all P < 0.05). However, there was no significant difference in the IL-4 level between the two groups (P > 0.05). Compared with the control group, there were also significant improvements in endothelial function-related indicators (vascular endothelial growth factor (VEGF), nitric oxide (NO), and peroxisome proliferator-activated receptor-γ (PPAR-γ)), blood lipid profile (total cholesterol (Tch), low-density lipoprotein cholesterol (LDL-C)), and chest pain related scores (angina and Traditional Chinese medicine syndrome scores) in the intervention group (all P<0.05). There was no significant difference in the triglyceride (TG) and carotid intima-media thickness between the two groups (P<0.05). Compared to the control group, there was no significant difference in the white blood cell line, liver and kidney function, anemia, and bleeding in the intervention group (all P<0.05). The addition of Guanxinning tablets (4 tablets, thrice daily) to the standard treatment strategy for ASCVD was associated with a reduction in the RIR in patients with SCAD and demonstrated good safety.

Chicoric acid exerts therapeutic effects in DSS-induced ulcerative colitis by targeting the USP9X/IGF2BP2 axis.

Chicoric acid, a hydroxycinnamic acid, exhibits anti-inflammation activities. However, the specific mechanisms underlying the effects of chicoric acid on dextran sulfate sodium (DSS)-induced colitis remain unclear. Here, we aimed to elucidate the molecular mechanisms underlying the protective effects of chicoric acid in DSS-induced colitis. Mice with DSS-induced colitis (UC mice) were treated for a week with chicoric acid. Symptoms of colitis, colonic pathology, inflammation-related indicators, and intestinal mucosal barrier function were evaluated. RNA sequencing was performed on colon tissues to obtain differentially expressed genes. The deubiquitinating enzyme USP9X was selected, and the inhibitory and targeting effects of chicoric acid on USP9X were subsequently determined. In vivo and in vitro, DSS-induced colitis was treated with USP9X inhibitors WP1130 and EOAI3402143. Ubiquitination label-free quantitative proteomic analysis was performed to identify protein peptides that may undergo de-ubiquitination by USP9X. Co-immunoprecipitation (Co-IP), immunohistochemistry and western blotting were used to validate in vivo and in vitro results. Chicoric acid significantly alleviated clinical activity and histological changes, inhibited pro-inflammatory cytokine production and improved integrity of the intestinal barrier in UC mice. Moreover, chicoric acid suppressed USP9X expression in colonic tissues from UC mice. Furthermore, USP9X contributed to promoting the onset of UC and that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) was deubiquitinated by USP9X. Chicoric acid ameliorated DSS-induced colitis by targeting the USP9X/IGF2BP2 axis, indicating that targeting the USP9X/IGF2BP2 axis presents a promising and innovative therapeutic approach for the treatment of UC.

ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway.

Adenosine deaminases acting on RNA 1 (ADAR1), an RNA editing enzyme, holds a role in cancer, inflammation, and immunity. However, its specific function in the nephropathy and high-glucose-induced human renal tubular epithelial cells (HK-2) injury in diabetic db/db mice is not clear. This study explored the expression characteristics of ADAR1 in proximal renal tubular cells of diabetic db/db mice, examining its function in the mechanism of high-glucose-induced HK-2 cell injury. Furthermore, it elucidated the molecular mechanism underlying the protective effect of ADAR1, the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt)/mammalian target of the rapamycin (mTOR) signaling. We observed a decrease in ADAR1 expression in proximal tubular cells of diabetic db/db mice, accompanied by an increase in the expression of inflammation-related markers (PI3K/AKT/mTOR). We constructed and validated ADAR1-overexpression plasmids and used an ADAR1 inhibitor (8-azaadenosine) to carry out cell experiments. The upregulation of ADAR1 expression alleviated high-glucose-induced endoplasmic reticulum stress, reduced HK-2 cell apoptosis, and reduced the expression of inflammation-related indicators (PI3K/AKT/mTOR). Taken together, the pivotal roles of ADAR1 in the progression of proximal renal tubulopathy and the mechanism of high-glucose-induced HK-2 injury in diabetic db/db mice suggest that ADAR1 may be a potential key factor in slowing the progression of diabetic kidney disease.

A Novel Nomogram Developed Based on Preoperative Immune Inflammation-Related Indicators for the Prediction of Postoperative Delirium Risk in Elderly Hip Fracture Cases: A Single-Center Retrospective Cohort Study.

Postoperative delirium (POD) commonly occurs in elderly individuals following hip fracture surgery, with unclear pathophysiological mechanism. Inflammation is a known factor affecting the onset of delirium. The current work aimed to examine the associations of preoperative immune inflammation-related indicators with POD occurrence in elderly cases following hip fracture surgery. The current retrospective cohort study included 437 elderly cases administered hip fracture surgery from January 2018 to December 2023. The clinicodemographic data and laboratory findings of all cases were retrospectively analyzed. Immune inflammation-related indicators were assessed, eg, MLR, NLR and PLR, as well as SII and SIRI. The bootstrap method was employed to assign cases at 7:3 to the training (48 and 258 cases in the POD and no-POD groups, respectively) and internal validation (13 and 118 cases in the POD and no-POD groups, respectively) cohorts. Next, LASSO, univariable and multivariable logistic regression analyses were applied to determine risk factors in the training cohort, based on which a nomogram model was built. The obtained nomogram was examined for accuracy by calibration plot analysis. Finally, the nomogram's clinical value was assessed by decision curve analysis (DCA), followed by internal validation based on the training cohort. Of all 437 cases, 61 developed POD, indicating a POD incidence of 13.96%. LASSO regression and multivariable analyses revealed preoperative SIRI independently predicted POD in the training cohort. The developed nomogram had an area under the curve (AUC) of 0.991 (95% CI 0.983~0.998) in the training cohort versus 0.986 (95% CI 0.966~1.000) in the validation cohort. Calibration curve analysis revealed nomogram-predicted and actual probabilities were in line. DCA demonstrated the novel nomogram could confer net benefits for POD prediction in elderly cases administered hip fracture surgery. The immune inflammation-related indicators SIRI could predict POD in elderly cases following hip fracture surgery.

Studies on the role of moderate doses of ionizing radiation-induced cellular senescence in mouse lung tissue

Purpose To investigate the role of moderate doses of ionizing radiation-induced cellular senescence in mouse lung tissue and whole-body inflammation levels. Material and methods Forty-two C57BL/6J mice were randomly divided into the control group, the 1, 3, and 7 days after 2 Gy irradiation group, and the 1, 3, and 7 days after 4 Gy irradiation group, with six mice in each group. The histopathology, cellular senescence, oxidative-antioxidant, DNA damage repair, and inflammation-related indicators of irradiated mice were examined. Results Compared with the control group, the histopathological scores, the positive area of senescence-associated-β-galactosidase (SA-β-Gal) staining, and the mRNA levels of senescence-related genes in the lung tissues in all dose groups increased on 1, 3, and 7 days after irradiation. In peripheral blood, erythrocytes, leukocytes, platelets, hemoglobin, 8-hydroxydeoxyguanosine (8-OHdG), C-reactive protein, and other indicators showed a different trend in all dose groups. The levels of malondialdehyde(MDA), superoxide dismutase (SOD), glutathione (GSH), and 8-OHdG in the lung tissue showed different trends after 2 Gy and 4 Gy irradiation. The 8-Oxoguanine DNA glycosylase 1 (hOGG1) and O-6-methylguanine-DNA methyltransferase (MGMT) mRNA levels showed a trend of increasing and then decreasing. The levels of whole-body inflammation were significantly correlated with the levels of indicators related to cellular senescence and damage repair in the lung tissue of mice. Conclusions The moderate doses of ionizing radiation induce oxidative stress, and DNA damage and increase DNA repair gene expression in mouse lung tissue. The lung tissue cellular senescence correlates with the level of whole-body inflammation.

The effect of preoperative supplementary parenteral nutrition on nutrition and inflammation in gastric cancer patients

ObjectivesSupplemental parenteral nutrition (SPN) is recommended to add when enteral nutrition alone is not sufficient. This research aims to evaluate the effect of preoperative SPN in patients with gastric cancer.MethodsA total of 180 patients with gastric cancer were divided into three groups (60 patients per group) according to different nutritional support scheme. The primary endpoint was the changes in nutrition and inflammatory, while the secondary endpoint included the changes in prognosis.ResultsCompared with the control group, there were significant differences in nutrition and inflammation related indicators in the oral nutrition supplement (ONS) group and the SPN + ONS group (P < 0.05). Compared with the ONS group, the SPN + ONS group showed significant differences in the above indicators (P < 0.05). However, no significant changes were observed in the incidence of complications, the postoperative exhaust time, and the hospitalization time.ConclusionsPreoperative SPN had a positive effect on nutrition and inflammation of gastric cancer patients undergoing surgery, but had no significant effect on their prognosis.

The role of sarcopenia in pre- and postoperative inflammation: implications of outcomes in patients with colorectal cancer

BackgroundPatients with colorectal cancer (CRC) with sarcopenia often have a poor prognosis, and the timing of preoperative intervention to improve sarcopenia is unclear. Sarcopenia can affect the body’s overall inflammatory status. This study aimed to investigate whether sarcopenia exacerbates the inflammatory response in patients with CRC after surgical stimulation and its effect on the prognosis. MethodsA retrospective analysis was conducted on a cohort of 215 patients with CRC who were categorized into either the sarcopenia group or the nonsarcopenia group based on their skeletal muscle index values. Inflammation-related indicators were collected from patients before and after surgery, allowing for the calculation of the differences in preoperative and postoperative changes. In addition, the correlation between inflammatory markers and postoperative complications was assessed. All patients were followed up for a period ranging from 2 to 5 years, with an average follow-up duration of 3 years, during which their recurrence and mortality rates were recorded. In addition, the relationship between inflammation indicators was explored. ResultsOf note, 45 of 215 patients with sarcopenia had higher levels of preoperative baseline inflammation markers, such as C-reactive protein (P = .002), immune-inflammation index (IBI; P < .001), systemic inflammatory response index (SIRI; P = .009), and systemic immune-inflammation index (SII; P = .002) than patients without sarcopenia. There was a significant difference in inflammatory indicators before and after surgery between dIBI, dSIRI, and dSII, with the largest effect observed. In addition, the predictive capabilities of dIBI, dSIRI, and dSII for postoperative complications, as measured using the area under the receiver operating characteristic curve, were found to be 0.938, 0.877, and 0.818, respectively. Furthermore, survival analysis indicated that the differences in preoperative and postoperative alterations in IBI (dIBI), SIRI (dSIRI), and SII (dSII) were effective in predicting long-term postoperative mortality. ConclusionOur findings suggest that sarcopenia plays a significant role in exacerbating postoperative inflammatory response in patients with CRC, leading to an increased risk of postoperative complications and influencing long-term survival outcomes.

Is systemic inflammation a missing link between cardiometabolic index with mortality? Evidence from a large population-based study

BackgroundThis study sought to elucidate the associations of cardiometabolic index (CMI), as a metabolism-related index, with all-cause and cardiovascular mortality among the older population. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), we further explored the potential mediating effect of inflammation within these associations.MethodsA cohort of 3029 participants aged over 65 years old, spanning six NHANES cycles from 2005 to 2016, was enrolled and assessed. The primary endpoints of the study included all-cause mortality and cardiovascular mortality utilizing data from National Center for Health Statistics (NCHS). Cox regression model and subgroup analysis were conducted to assess the associations of CMI with all-cause and cardiovascular mortality. The mediating effect of inflammation-related indicators including leukocyte, neutrophil, lymphocyte, systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) were evaluated to investigate the potential mechanism of the associations between CMI and mortality through mediation package in R 4.2.2.ResultsThe mean CMI among the enrolled participants was 0.74±0.66, with an average age of 73.28±5.50 years. After an average follow-up period of 89.20 months, there were 1,015 instances of all-cause deaths and 348 cardiovascular deaths documented. In the multivariable-adjusted model, CMI was positively related to all-cause mortality (Hazard Ratio (HR)=1.11, 95% CI=1.01-1.21). Mediation analysis indicated that leukocytes and neutrophils mediated 6.6% and 13.9% of the association of CMI with all-cause mortality.ConclusionElevated CMI is positively associated with all-cause mortality in the older adults. The association appeared to be partially mediated through inflammatory pathways, indicating that CMI may serve as a valuable indicator for poor prognosis among the older population.

Evaluation of Menopausal Syndrome Relief and Anti-Obesity Efficacy of the Korean Fermented Food Doenjang: A Randomized, Double-Blind Clinical Trial.

Foods that help improve menopausal syndrome are being studied worldwide. Doenjang is a traditional Korean fermented soybean food with potential health benefits for menopausal women. In this clinical trial using Doenjang, we aimed to compare the effectiveness of traditional Doenjang and commercial Doenjang in menopausal women. Furthermore, we compared whether Doenjang has a better effect if the number of beneficial microbes is higher. The analyses included the following groups: traditional Doenjang containing either a high dose (HDC; n = 18) or low dose (LDC; n = 18) of beneficial microbes and commercial Doenjang (CD; n = 20). The Kupperman index and hematological changes were examined before and after the use of Doenjang pills. The effects of Doenjang on obesity and body composition were studied before and after ingestion. Lastly, the microorganisms and short-chain fatty acid changes in the stool were compared. The Kupperman index decreased after Doenjang consumption in all three groups, with the greatest decrease in the LDC group. Only the groups that took traditional Doenjang pills exhibited reduced LDL cholesterol. No changes in obesity and inflammation-related indicators were observed. The number of Firmicutes, associated with obesity, decreased in the CD group but the numbers of Bacteroidetes increased in the HDC and CD groups. Thus, traditional Doenjang is more effective in alleviating menopausal syndrome than commercial Doenjang. Further research on the anti-obesity effect or changes in microbiomes and short-chain fatty acids in feces is needed.

The role of peripheral inflammation-related biomarkers in distinguishing Parkinson's disease

BackgroundPeripheral inflammation plays a significant role in Parkinson's disease (PD). Conflicting studies on whether inflammatory indicators in blood could serve as biomarkers to distinguish PD. ObjectiveInclude a wider range of biomarkers and control confounding factors to comprehensively evaluate the value of peripheral inflammation-related indicators. MethodsA total of 80 PD patients were recruited and 80 one-to-one matched healthy controls (HCs). The levels of B-cell, T-cell, and natural killer (NK)-cell in blood were measured using flow cytometry. The levels of neurodegeneration-related proteins in serum were detected and clinical blood test results were collected. Multivariable logistic regression analysis was conducted to explore the role of significant variables in PD. Receiver operating characteristic curve analysis was performed to assess the potential value of these variables. ResultsCompared to HCs, PD patients showed lower levels of lymphocyte, B-cell, T-cell, high-density lipoprotein cholesterol (HDL-C) and lymphocyte-to-monocyte ratio, while the levels of neutrophil, NK-cell, β-amyloid40, neurofilament light chain, neutrophil-to-lymphocyte ratio, and neutrophil-to-HDL-C ratio (NHR) were increased. A higher B-cell count was associated with a lower risk of PD, while higher levels of NK-cell and NHR were associated with a higher risk of PD. B-cell, NK-cell and NHR have potential value in distinguishing PD from non-PD. B-cell and NHR levels were significantly correlated with PD dyskinesia scores. ConclusionsB-cell, NK-cell, and NHR may potentially contribute to distinguishing PD patients from HCs. There could be a correlation between the number of B-cell, the level of NHR, and the severity of PD dyskinesia.

The Role of Hepcidin, sTfR, and sTfR/Log Ferritin Index for the Differential Diagnosis of Iron Deficiency Anemia and Anemia of Chronic Disease

Background: In chronic diseases characterized by persistent inflammation, anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are commonly encountered forms of anemia and can often co-occur. In such situations, the conventional iron status tests used for differential diagnosis are influenced by inflammation, reducing their diagnostic accuracy. The primary objective of this study was to assess the significance of hepcidin as a crucial diagnostic marker for ACD and to investigate the correlation between hepcidin and inflammation-related indicators. Furthermore, a significant secondary aim of this research was to ascertain the diagnostic role of novel biochemical markers, specifically soluble transferrin receptor (sTfR) and the derived sTfR/log ferritin index (sTfR-F index). Methods and Results: This study was conducted at the Laboratory Service of the University Hospital Center "Mother Teresa" and included a cohort of 187 subjects, comprising 156 patients (83 females and 73 males) who were admitted to and received treatment at the Rheumatology and Cardiology Departments of the "Mother Teresa" University Hospital Center in Tirana. Additionally, 31 individuals without anemia and inflammatory conditions were included as a control group. All subjects incorporated into the study were classified into five distinct groups based on a comprehensive analysis of their complete blood profiles, iron status, and inflammation-related biomarkers: IDA, ACD, ACD+IDA, RA/CHF patients without anemia, and the control group without anemia. The comparison between groups showed that the mean values of pro-hepcidin, TNFα, IL6, Hs-PCR, and ferritin are significantly decreased in IDA vs. ACD, while sTFR and sTfR-F index are significantly increased. In comparing ACD vs. ACD+IDA groups, ferritin increased significantly in the ACD group, while sTFR and sTfR-F index decreased significantly in ACD, compared to the ACD+IDA group. The ROC curves analysis of the biochemical parameters selected for the comparison of ACD vs IDA showed that the pro-hepcidin test is a perfect test for the differential diagnosis of ACD vs. IDA. The suggested cut-off value for pro-hepcidin was ≥153 ng/ml, yielding a sensitivity of 100% and a specificity of 100% for the diagnosis of ACD. As regards sTFR, the suggested cut-off value for the diagnosis of IDA vs. ACD was≥ 4.9 µg/ml resulting in 84% sensitivity and 100% specificity. The sTfR-F index was also very useful for the diagnosis of IDA vs. ACD: for a cut-off value of ≥2.06, the sensitivity was 90% and the specificity was 96%. sTfR resulted in a good test for the diagnosis of ACD+IDA vs. ACD: the cut-off value was ≥ 3.7µ/ml, the sensitivity was 92.3% and the specificity was 93.2%. Similarly, the parameter sTfR-F index resulted in a very good test for the diagnosis of ACD+IDA vs. ACD: for the suggested cut-off value of ≥2.3, the sensitivity was 92.3% and the specificity was 100%. Conclusion: As a result of the study, it was found that the pro-hepcidin test was a highly accurate test for distinguishing between ACD and IDA. Meanwhile, sTfR and the sTfR-F index proved to be excellent indicators for the differential diagnosis of IDA in chronic inflammatory conditions.

Role of clinical pharmacists in multidisciplinary collaborative management of blood glucose in COVID-19 patients with hyperglycemia

BackgroundDuring the ongoing global pandemic of COVID-19, the association between hyperglycemia and COVID-19 infection has emerged as a notable concern. Therefore, finding effective methods to manage hyperglycemia in patients with COVID-19 is crucial. ObjectiveTo introduce the clinical pharmacists participating in multidisciplinary collaborative whole hospital blood glucose management mode, and to explore its effect on blood glucose control in patients with coronavirus disease 2019 infection and complicated with hyperglycemia. MethodsPatients with COVID-19 treated at Nanjing Drum Tower Hospital from December 2022 to January 2023 were assigned to routine diagnosis and treatment group and whole hospital blood glucose management group according to the blood glucose management plan received by patients. The groups were compared in regards to their adherence to management advice, blood glucose levels, fluctuation, inflammation-related indicators, medical service-related indicators, and incidence of hypoglycemia and adverse events. ResultsAfter 5 days of glucose management, both groups showed a decrease in fasting and postprandial blood glucose. Postprandial blood glucose in the whole hospital glucose management group was significantly lower than the routine group (P < 0.05). The whole hospital glucose management group showed a significant increase in compliance rate, improved inflammation-related indicators, and higher detection rates for hemoglobin and islet function (P < 0.05). Implementation rates for medical orders and treatment plans were also higher in the whole hospital group (P < 0.05). There was no significant difference in incidence of adverse events. ConclusionsMultidisciplinary blood glucose management is highly recommended for patients with COVID-19 who have hyperglycemia due to its effectiveness, standardization, safety, and improvement of inflammation indicators.

Association of lymphocyte count and serum albumin concentration with telomere length in Chinese sanitation workers.

This study aimed to examine the association between inflammation-related indicators (IRIs) and telomere length (TL) in Chinese sanitation workers. This study adopted a case-control design, conducted from January to December 2022 in Shenzhen, a city in eastern China. A total of 80 sanitation workers, as well as 80 matched controls, were randomly recruited from the Luohu district of Shenzhen city in China. Their blood samples were collected and analyzed for the IRIs and TL in the Medical Laboratory of Shenzhen Prevention and Treatment Center for Occupational Diseases. The relationship between IRIs and TL was analyzed using multivariate linear regression, and their dose-response relationship was explored using restricted cubic spline analysis. The systemic inflammatory index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were significantly elevated in the sanitation workers in comparison to the controls. Moreover, the lymphocyte count (LYM), serum albumin concentration (ALB), and TL were found to be lower in the sanitation workers compared to the controls (P < 0.05). After adjusting for potential confounding variables, LYM was negatively correlated with TL in the sanitation workers (β = -0.31, 95% CI: -0.57, -0.05), whereas no correlation was observed in the controls. Furthermore, ALB demonstrated a non-linear relationship with TL in sanitation workers. We found higher novel inflammatory markers (SII, PLR, and NLR) in the sanitation workers, and identified a correlation between LYM and ALB with shortened TL in them, providing new evidence for the effect of elevated inflammation on accelerated aging in Chinese sanitation workers.

Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.

Gansui Banxia decoction modulates immune-inflammatory homeostasis to ameliorate malignant ascites in rats

Background“Gansui Banxia decoction” (GBD) is a classical traditional Chinese medicine formula for treating abnormal accumulation of fluid, such as malignant ascites (MA). Although GBD has shown definite water-expelling effects, its exact underlying mechanism has not been elucidated. PurposeThis study aimed to investigate the drug effects of GBD on MA rats and its underlying mechanisms. MethodsThe main chemical composition was determined by ultra-high performance liquid chromatography. The drug effects of GBD was evaluated in the established cancer cell-induced MA rat model. The symptoms were analyzed, and biological samples were collected for detecting immune and inflammation-related indicators by enzyme-linked immunosorbent assays, western blot, and flow cytometry. ResultsGBD increased urine discharge, decreased ascites production, and alleviated cachexia. After GBD treatment, the expression of TLR4, MyD88, and NF-кB and the release of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were reduced. In addition, GBD increased G1 phase arrest and inhibit excessive proliferation of cells in bone marrow while alleviating G1 phase arrest and increasing proliferation of cells in the thymus. Correspondingly, the development and maturation of T cells also changed. GBD increased the proportion of mature T-cells (CD4+CD8− and CD4−CD8+ single-positive (SP) T-cells), and decrease the proportion of immature cells (CD4+CD8+ double-positive (DP) T-cells and CD4−CD8− double-negative (DN) T-cells) in the blood or tumor microenvironment (TME, the ascites microenvironment). Finally, we further analysis of immune cell subsets, GBD decreased the proportion of immunosuppressive T-cells in the blood (CD4+CD25+Foxp3+T-cells) and TME (CD8+CD25+Foxp3+T-cells), and increased the proportion of anti-tumor immune cells (CD8+CD28+T-cells and NK cells) in the TME. ConclusionThese findings indicated that the drug effects of GBD were attributed to regulating the immune-inflammatory homeostasis, thereby mitigating the destruction of cancer cells and reducing the generation of ascites, which provided theoretical support for the clinical rational application and extended the scientific connotation of “water-expelling” of GBD.

SeMet alleviates LPS-induced eggshell gland necroptosis mediated inflammation by regulating the Keap1/Nrf2/HO-1 pathway

Exposure to lipopolysaccharide (LPS) can lead to inflammation in a variety of tissues and organs. Selenium (Se) plays a crucial role in mitigating inflammatory damage. Compared with inorganic selenium, organic selenium, such as selenomethionine (SeMet), has the advantages of a higher absorption rate and lower toxicity in animals. This study examined the protective effects of SeMet on eggshell gland tissue damage caused by LPS. Hy-Line Brown laying hens were chosen as the experimental animals and were randomly assigned to four groups: control group (C), lipopolysaccharide group (LPS), SeMet group (Se), and SeMet + lipopolysaccharide group (Se + LPS). H&E staining and transmission electron microscope were performed to observe the pathological changes of eggshell glands, oxidative stress related indicators were measured using relevant kits, qRT‒PCR and western blotting were used to evaluate the mRNA and protein levels of the Nrf2 pathway, necroptosis, and inflammation related indicators. The results showed that LPS treatment increased the content of malondialdehyde (MDA), decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and decreased the content of glutathione (GSH). LPS increased the levels of Keap1, RIPK1, RIPK3, MLKL, TNF-α, COX-2, and NF-κB, while decreasing the levels of HO-1, NQO1, Nrf2, and Caspase-8. However, SeMet treatment effectively reversed the changes of the above indicators, indicating that SeMet alleviates eggshell gland cell necroptosis-mediated inflammation induced by LPS via regulating the Keap1/Nrf2/HO-1 pathway. This study elucidated the mechanism by which SeMet alleviates LPS-induced eggshell gland tissue damage in Hy-Line Brown laying hens and provided a new direction for expanding the application of SeMet in the feeding and production of laying hens.

Atorvastatin Promotes Pro/anti-inflammatory Phenotypic Transformation of Microglia via Wnt/β-catenin Pathway in Hypoxic-Ischemic Neonatal Rats.

Inflammatory reaction plays a key role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonates. Microglia are resident innate immune cells in the central nervous system and are profoundly involved in neuroinflammation. Studies have revealed that atorvastatin exerts a neuroprotective effect by regulating neuroinflammation in adult animal models of brain stroke and traumatic brain injury, but its role regarding damage to the developing brain remains unclear. This study aimed to clarify the effect and mechanism of atorvastatin on the regulation of microglia function in neonatal hypoxic-ischemic brain damage (HIBD). The oxygen glucose deprivation (OGD) of microglia and neonatal rat HIBD model was established. Atorvastatin, recombinant sclerostin protein (SOST), and XAV939 (degradation of β-catenin) were administered to OGD microglia and HIBD rats. The pathological changes of brain tissue, cerebral infarction volume, learning and memory ability of rats, pro-inflammatory (CD16+/Iba1+) and anti-inflammatory (CD206+/Iba1+) microglia markers, inflammation-related indicators (Inos, Tnfα, Il6, Arg1, Tgfb, and Mrc1), and Wnt/β-catenin signaling molecules were examined. Atorvastatin reduced OGD-induced pro-inflammatory microglia and pro-inflammatory factors, while increasing anti-inflammatory microglia and anti-inflammatory factors. In vivo, atorvastatin attenuated hypoxia-ischemia (HI)-induced neuroinflammation and brain damage. Mechanistically, atorvastatin decreased SOST expression and activated the Wnt/β-catenin signaling pathway, and the administration of recombinant SOST protein or XAV939 inhibited Wnt/β-catenin signaling and attenuated the anti-inflammatory effect of atorvastatin. Atorvastatin promotes the pro/anti-inflammatory phenotypic transformation of microglia via the Wnt/β-catenin pathway in HI neonatal rats. Atorvastatin may be developed as a potent agent for the treatment of HIE in neonates.

Effect of single intravenous injection of esketamine on postpartum depression after labor analgesia and potential mechanisms: a randomized, double-blinded controlled trial

BackgroundThe study was designed to investigate effects of single intravenous injection of esketamine on the incidence of postpartum depression (PPD) after labor analgesia and explore the potential mechanisms.MethodsA total of 120 women who underwent labor analgesia by epidural analgesia pump were enrolled and divided into two groups randomly. Esketamine at a dose of 0.2 mg/kg was intravenously injected after fetal disengagement in the test group and placebo was administered in the control group. The occurrence of PPD and side effects after delivery were recorded. Some indicators related to stress and inflammation were measured before labor analgesia and at 24 h, 1 week, and 6 weeks after delivery in this study. Data were analyzed by independent t-test, repeated measures analysis of variance and Chi-square test in SPSS software (version 25.0). It was considered statistically significant since a p value less than 0.05.ResultsThe incidence of PPD was significantly decreased both for one week and six weeks after delivery by using of esketamine (3.4% vs. 15.3%, p = 0.004 and 5.2% vs. 18.6%, p = 0.006, respectively). There were also significant differences between the stress and inflammation-related indicators in different time points in this study, while the side effects for 48 h after delivery were similar between the two groups.ConclusionsSingle intravenous injection of esketamine after delivery in participants underwent labor analgesia can decrease the occurrence of postpartum depression for one week and six weeks after delivery, while the side effects were not increased. The antidepressant effects of esketamine may be related to the reduction of stress response and inflammation.Trial registrationThe trial was registered at the Chinese Clinical Trial Registry on 5/30/2022 (CTRI registration number—ChiCTR2200060387). URL of registry: https://www.chictr.org.cn/bin/home.

Fenpropathrin induces neurotoxic effects in common carp (Cyprinus carpio L.)

Fenpropathrin (FEN) is a synthetic pyrethroid that has been frequently detected in aquatic environments, yet the neurotoxic impacts and underlying mechanisms on nontarget organisms are lacking. In this experiment, common carp were exposed to 0.45 and 1.35 μg/L FEN for 14 d and exhibited abnormal locomotor behaviour. Biochemical and molecular analysis results indicated that FEN altered the contents of tight junction proteins (claudin-1, occludin, and ZO-1), disturbed Na+-K+-ATPase and AChE activities, caused abnormal expression of neurotransmitters (ACh, DA, GABA, 5-HT, and glutamate) and caused histological damage in the brain, suggesting that FEN may damage the blood–brain barrier and induce neurotoxicity in carp. Furthermore, FEN also promoted an increase in ROS, changed SOD and CAT activities, and generally upregulated the contents of MDA, 8-OHdG, and protein carbonyl in the brain, indicating that FEN can induce oxidative stress and cause damage to lipids, DNA, and proteins. Moreover, inflammation-related indicators (TNF-α, IL-1β, IL-6, and IL-10), mitophagy-related genes (PINK1, parkin, ulk1, beclin1, LC3, p62, tfeb, and atg5), and apoptosis-related parameters (p53, bax, bcl-2, caspase-3, caspase-8, and caspase-9) were also significantly changed, suggesting that inflammation, mitophagy, and apoptosis may participate in FEN-induced neurotoxicity in carp. This study refines the understanding of the toxicity mechanism of FEN and thus provides data support for the risk assessment of FEN.