SZ168 treats LPS-induced acute lung injury by inhibiting the activation of NF-κB and MAPKs pathways.

BACKGROUND: This study aimed to elucidate the effect and underlying molecular mechanisms of SZ168 (Podoplanin (PDPN) monoclonal antibody) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and LPS-induced MH-S cells. METHODS: The survival rate was calculated by recording the death of mice in each group. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of interleukin (IL)- 6 and tumor necrosis factor-alpha (TNF-α) in blood and bronchoalveolar lavage fluid (BALF) of mice. Hematoxylin-eosin (H&E) staining were performed to evaluate the pathological changes in pulmonary tissues. Additionally, the phagocytosis of cells was tested by flow cytometry, and the expression levels of caveolin-1 (CAV-1) and Occludin proteins in lung tissue and the expression of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway-related proteins in MH-S cells were determined by western blot. RESULTS: SZ168 significantly improved the survival rate of ALI mice. Briefly speaking, SZ168 protected pulmonary vascular permeability, reduced the level of pro-inflammatory cytokines, improved the pathological changes of lung tissue, reduced the infiltration of inflammatory cells, increased CAV-1 and Occludin protein expression, and then effectively relieved lung injury. In addition, SZ168 could significantly reduce the phagocytic ability of LPS-induced MH-S cells and inhibit the expression of hospho-extracellular regulated protein kinases (p-ERK), Phospho-Jun N-terminal kinase (p-JNK), Phospho-NF-κB p65 (p-p65) and Phospho-IkappaB-alpha (p-IκBα). CONCLUSION: SZ168 can treat ALI by inhibiting the activation of NF-κB and MAPK signaling pathways and restoring tight junction protein expression.

miR-106a Targets Anoctamin 1 (ANO1) to Regulate Lipopolysaccharide (LPS)-Induced Inflammatory Response in Macrophages.

BACKGROUND Sepsis is an organ dysfunction characterized by systemic inflammatory response. Micro(mi)ribonucleic acids take part in the regulation of the inflammatory response in many conditions. However, the role and mechanism of miR-106a and anoctamin 1 (ANO1) in the inflammatory response in sepsis remain largely unknown. MATERIAL AND METHODS The serum samples were collected from 31 sepsis patients and healthy volunteers. Lipopolysaccharide (LPS)-treated RAW264.7 cells were used for the study in vitro. The inflammatory response was investigated via interleukin-6 and tumor necrosis factor-alpha levels using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay. The expression abundances of miR-106a and ANO1 were detected via qRT-PCR or western blot. The target association between miR-106a and ANO1 was explored using dual-luciferase reporter analysis. RESULTS The inflammatory response was trigged in sepsis and LPS-treated RAW264.7 cells. miR-106a expression was enhanced and ANO1 declined in sepsis and LPS-treated RAW264.7 cells. Overexpression of ANO1 suppressed the inflammatory response and knockdown of ANO1 promoted the inflammatory response in RAW264.7 cells. ANO1 was directly targeted via miR-106a, and miR-106a reversed ANO1-mediated inflammatory inhibition in LPS-treated RAW264.7 cells. CONCLUSIONS MiR-106a regulated LPS-induced inflammatory response by targeting ANO1 in RAW264.7 cells, indicating the potential value of miR-106a for treatment of inflammatory diseases, including sepsis.

[Effects of body temperature on the prognosis of patients with septic shock].

OBJECTIVE: To observe the effects of abnormal body temperature and the area under temperature curve on the prognosis of patients with septic shock. METHODS: A retrospective cohort study was conducted. Patients with septic shock admitted to intensive care unit (ICU) of Wuxi People's Hospital Affiliated to Nanjing Medical University from September 2013 to June 2019 were enrolled. Data were obtained from the hospital case database, including the gender, age, infection source, the length of ICU stay, sequential organ failure assessment (SOFA) score, 21-day prognosis; within the first 24 hours and throughout the period in ICU, the maximum temperature (24 h Tmax, Tmax), lowest temperature (24 h Tmin, Tmin), and the temperature range (24 h Tmax-min, Tmax-min) were aggregated. The area under temperature curve when body temperature was higher than T (A> T), or lower than T (A< T), and area section between T1 and T2 (AT1-T2) was calculated respectively. Patients were divided into survival group and death group according to 21-day prognosis. Binary Logistic regression was used to analyze the effect of the above temperature indices on the prognosis. RESULTS: 635 septic shock patients were enrolled in the study. 476 patients were survived and 159 died within 21 days. Compared with the survival group, the age, SOFA score were higher in the death group, while the length of ICU stay was shorter. There was no significant difference in gender or infection source between two groups. After adjusting for gender, age, the length of ICU stay and SOFA score, binary Logistic regression analysis showed that the increase of Tmax, decrease of Tmin, and increase of Tmax-min were risk factors for 21-day mortality [Tmax: odds ratio (OR) = 2.959, 95% confidence interval (95%CI) was 1.620-5.398, P > 0.001; Tmin: OR = 0.329, 95%CI was 0.140-0.790, P = 0.012; Tmax-min: OR = 3.258, 95%CI was 1.840-5.471, P > 0.001], while 24 h Tmax, 24 h Tmin and 24 h Tmax-min were not related to prognosis. A< 36.0 centigrade (OR = 1.335, 95%CI was 1.102-1.745, P = 0.014), and A> 38.0 centigrade (OR = 1.041, 95%CI was 1.019-1.077, P = 0.001) showed positive correlation with 21-day mortality. When the T level was set at 38.0-40.0 centigrade, for every 1 centigrade×hour increase in A> T, the 21-day relative risk of death increased by 4.1%-83.2%. CONCLUSIONS: When the body temperature of patients with septic shock is lower than 36.0 centigrade, or higher than 38.0 centigrade, the 21-day relative risk of death rose with the increase of the magnitude and duration of abnormal body temperature.

Relationship between disease severity and thyroid function in Chinese patients with euthyroid sick syndrome.

Euthyroid sick syndrome (ESS) is commonly observed in various acute and chronic illness as risk factor for mortality in patients with severe diseases, with lower triiodothyronine (T3) and free triiodothyronine (fT3).To explore the relationship between disease severity and thyroid function in critically ill Chinese patients with ESS.A total of 51 patients admitted to intensive care unit were examined to determine acute physiology and chronic health assessment II (APACHE II) scores within 24 hours of admission; thyroid function tests (TSH, fT3, fT4, tT3, tT4) and rT3 levels were determined on the second day. Based on the test results, patients were divided into euthyroid (n = 13), decreased fT3 or fT4 (n = 17), and decreased TSH (n = 21) groups. APACHE II scores and thyroid function were compared between the 3 groups. Furthermore, the relationship between the severity of disease and euthyroid sick syndrome was assessed.Out of 51 patients, 38 were men and 13 were women [mean age (± SD): 60.39 (± 19.32) years; range, 15-88 years]. APACHE II scores and rT3 levels were increased in all the 3 groups (P > .05). APACHE II scores showed a positive correlation with rT3 (P = .004, r = 0.379).Critically ill Chinese patients with ESS have a poor health state. Higher rT3 values are associated with severe disease.