Arbidol increases the survival rate by mitigating inflammation in suckling mice infected with human coronavirus OC43 virus.

Human coronavirus OC43 (HCoV-OC43) often causes common cold and is able to neuroinvasive, but it can also induce lower respiratory tract infections (LRTI) especially in children and the elderly adults with underlying diseases. HCoV-OC43 infections currently have no approved antiviral treatment. Arbidol (ARB) is a broad-spectrum antiviral and is an antiviral medication for the treatment of influenza used in Russia and China. Due to its multiple mechanisms of action, such as inhibition of viral fusion and entry, immunomodulation, and modulation of host cell signaling pathways, ARB has the potential to be an effective treatment option for viral infections. Therefore, the study aims to investigate the activities of ARB against HCoV-OC43 infections. Suckling mice were infected with HCoV-OC43 and treated with ARB (50, 25 and 12.5 mg/kg/d) by gavage once daily for 4 days. the survival rates and body weight were recorded, the viral titer was measured by real-time quantitative polymerase chain reaction, cytokine levels were measured by Bio-Plex assays. Histopathological changes of the lungs and brain were analyzed. Our results show ARB increased the survival rate, reduced viral copy numbers in the lung, mitigated pro-inflammatory cytokine production, and improved brain and lung histopathology significantly without any significant toxicity or side effects in vivo. Our results suggest ARB could be a promising approach for the prevention and treatment of HCoV-OC43 while further studies are needed to address these possibilities and the underlying mechanism.

Cardiac arrest secondary to pulmonary embolism treated with extracorporeal cardiopulmonary resuscitation: Six case reports.

BACKGROUND: Massive pulmonary embolism (PE) results in extremely high mortality rates. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide circulatory and oxygenation support and rescue patients with massive PE. However, there are relatively few studies of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with cardiac arrest (CA) secondary to PE. The aim of the present study is to investigate the clinical use of ECPR in conjunction with heparin anticoagulation in patients with CA secondary to PE. CASE SUMMARY: We report the cases of six patients with CA secondary to PE treated with ECPR in the intensive care unit of our hospital between June 2020 and June 2022. All six patients experienced witnessed CA whilst in hospital. They had acute onset of severe respiratory distress, hypoxia, and shock rapidly followed by CA and were immediately given cardiopulmonary resuscitation and adjunctive VA-ECMO therapy. During hospitalization, pulmonary artery computed tomography angiography was performed to confirm the diagnosis of PE. Through anticoagulation management, mechanical ventilation, fluid management, and antibiotic treatment, five patients were successfully weaned from ECMO (83.33%), four patients survived for 30 d after discharge (66.67%), and two patients had good neurological outcomes (33.33%). CONCLUSION: For patients with CA secondary to massive PE, ECPR in conjunction with heparin anticoagulation may improve outcomes.

Simultaneous profiling and quantification of 25 eicosanoids in human serum by ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry.

The eicosanoid metabolic pathway is responsible for mediating the production of various inflammatory factors that are closely related to the development and resolution of inflammation. In biological matrices, the major quantifying obstacles were shown to be the oxidation and low quantities of eicosanoids and their metabolites. This study aimed to develop a reliable, sensitive ultrahigh-performance liquid chromatography coupled to a tandem mass spectrometry (UPLC-MS/MS) method to quantify eicosanoids in human serum. Solid-phase extraction (SPE) was used for sample preparation. The approach employed continuous ionization polarity switching. The target eicosanoids showed good linearity over the investigated concentration range (r2 > 0.99). The recovery rates were over 64.5%, and the matrix effects ranged from 73.0 to 128.0%. The limits of quantification were 0.048 ~ 0.44 ng/mL. For the broad concentration range, the CV % for accuracy and precision were less than ± 20%. We successfully applied this method to rapidly analyse 74 serum samples from severe influenza pneumonia, severe bacterial pneumonia and healthy individuals. Eicosanoid-related metabolite concentrations were quantified within a range similar to those of previously published articles. Compared to healthy individuals, our application found that 20-HETE, 14,15-EET and 11,12-EET were upregulated in severe influenza pneumonia patients, while LTB4 was downregulated. 8-HETE and 5-HETE were upregulated in severe bacterial pneumonia patients, while LTE4 was downregulated. This approach provides a means for monitoring the low quantities of eicosanoids in biological matrices, and our finding that different characteristic metabolite profiles may help discriminate the induction of severe pneumonia patients.

Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19.

Background: The current COVID-19 pandemic is posing a major challenge to public health on a global scale. While it is generally believed that severe COVID-19 results from over-expression of inflammatory mediators (i.e., a "cytokine storm"), it is still unclear whether and how co-infecting pathogens contribute to disease pathogenesis. To address this, we followed the entire course of the disease in cases with severe or critical COVID-19 to determine the presence and abundance of all potential pathogens present-the total "infectome"-and how they interact with the host immune system in the context of severe COVID-19. Methods: We examined one severe and three critical cases of COVID-19, as well as a set of healthy controls, with longitudinal samples (throat swab, whole blood, and serum) collected from each case. Total RNA sequencing (meta-transcriptomics) was performed to simultaneously investigate pathogen diversity and abundance, as well as host immune responses, in each sample. A Bio-Plex method was used to measure serum cytokine and chemokine levels. Results: Eight pathogens, SARS-CoV-2, Aspergillus fumigatus (A. fumigatus), Mycoplasma orale (M. orale), Myroides odoratus (M. odoratus), Acinetobacter baumannii (A. baumannii), Candida tropicalis, herpes simplex virus (HSV) and human cytomegalovirus (CMV), identified in patients with COVID-19 appeared at different stages of the disease. The dynamics of inflammatory mediators in serum and the respiratory tract were more strongly associated with the dynamics of the infectome compared with SARS-CoV-2 alone. Correlation analysis revealed that pulmonary injury was directly associated with cytokine levels, which in turn were associated with the proliferation of SARS-CoV-2 and co-infecting pathogens. Conclusions: For each patient, the cytokine storm that resulted in acute lung injury and death involved a dynamic and highly complex infectome, of which SARS-CoV-2 was a component. These results indicate the need for a precision medicine approach to investigate both the infection and host response as a standard means of infectious disease characterization.

[Protection of curcumin to intestinal mucosal barrier by inhibiting enterocyte apoptosis in septic rats].

OBJECTIVE: To study the effect of curcumin on enterocyte apoptosis and its protective effect on intestinal mucosal barrier in septic rats. METHODS: Eighty-seven 3-month male Sprague-Dawley (SD) rats were divided into Sham group, model group and curcumin group by random number table method, with 29 rats in each group. The septic rat model was reproduced by cecal ligation and puncture (CLP). 4 mL dimethyl sulfoxide solution were intraperitoneally injected in both Sham group and model group, 200 mg/kg curcumin dissolved by 4 mL dimethyl sulfoxide solution were intraperitoneally injected in curcumin group 10 minutes after operation. The blood samples (15 rats in each group) were collected 2, 12, 24 hours after operation, and the levels of serum procalcitonin (PCT), tumor necrosis factor-α (TNF-α), D-lactic acid and diamine oxidas (DAO) were tested by enzyme linked immunosorbent assay (ELISA). The ileum tissues were collected 12 hours, 24 hours after operation in three groups, water content was tested by weighting, pathologic structure was observed by light microscope, the enterocyte apoptosis was tested by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling method (TUNEL). The 7-day survival rate was observed in three groups (14 rats in each group). RESULTS: The serum levels of PCT, TNF-α, D-lactic acid and DAO were higher in model group at 2, 12, 24 hours after operation than those in Sham group, PCT, TNF-α levels were significantly higher in model group than those in Sham group 2 hours after operation [PCT (µg/L): 1.89±0.17 vs. 0.10±0.02, TNF-α (ng/L): 216.51±1.47 vs. 85.25±8.20, both P < 0.01], D-lactic acid, DAO levels were significantly higher in model group than those in Sham group 12 hours after operation [D-lactic acid (mg/L): 40.53±7.76 vs. 11.29±1.28, DAO (ng/L): 1 120.40±302.35 vs. 330.02±81.28, both P < 0.01]. Compared with model group, the levels of serum PCT, TNF-α, D-lactic acid and DAO were lower in curcumin group 2, 12, 24 hours after operation, the statistical difference appeared from 12 hours after operation [PCT (µg/L): 5.37±0.44 vs. 8.67±0.64, TNF-α (ng/L): 211.12±4.31 vs. 313.30±18.46, D-lactic acid (mg/L): 29.74±1.41 vs. 40.53±7.76, DAO (ng/L): 810.71±201.41 vs. 1 120.40±302.35, all P < 0.05], curcumin group had lower water content in ileum tissues 12 hours, 24 hours after operation [(68.34±0.68)% vs. (70.55±0.87)%, (69.41±0.59)% vs. (71.69±0.87)%, both P < 0.05]. The pathologic structures of intestinal villus were normal in Sham group, however, in model group intestinal villus were atrophic, edematous and shorten 12 hours after operation, it was further exacerbated 24 hours after operation. Compared with model group, the pathologic structures of intestinal villus in curcumin group were relived 12 hours, 24 hours after operation. The number of apoptotic enterocytes were significantly increased in model group compared with Sham group 24 hours after operation (cells: 25.48±6.10 vs. 4.00±2.04, P < 0.05), and the number of apoptotic enterocytes was lower in curcumin group than that in model group at the same time (cells: 15.48±3.75 vs. 25.48±6.10), the difference was statistically significant (both P < 0.05). Seven-day survival rate was significantly lower in curcumin than that in model group [42.9% (6/14) vs. 50.0% (7/14)], however, the difference was not statistically significant (P > 0.05). CONCLUSIONS: Curcumin can protect the intestinal mucosal barrier by inhibiting enterocyte apoptosis in septic rats.

Human post-infection serological response to the spike and nucleocapsid proteins of SARS-CoV-2.

To inform seroepidemiological studies, we characterized the IgG- responses in COVID-19 patients against the two major SARS-CoV-2 viral proteins, spike (S) and nucleocapsid (N). We tested 70 COVID-19 sera collected up to 85 days post-symptom onset and 230 non-COVID-19 sera, including 27 SARS sera from 2003. Although the average SARS-CoV-2 S and N-IgG titers were comparable, N-responses were more variable among individuals. S- and N-assay specificity tested with non-COVID-19 sera were comparable at 97.5% and 97.0%, respectively. Therefore, S will make a better target due to its lower cross-reactive potential and its' more consistent frequency of detection compared to N.

[Protective effect of curcumin on hepatocytes in rats with sepsis].

OBJECTIVE: To investigate the protective effect of curcumin on hepatocytes in rats with sepsis. METHODS: Eighty healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, Xuebijing group and curcumin group (20 rats in each group) according to the random number table method. The animal model of sepsis was established by cecal ligation and puncture (CLP). In the sham operation group, the cecum was removed only after the operation. The rats in Xuebijing group and curcumin group were injected with 4 mL/kg Xuebijing, 100 mg/kg curcumin intraperitoneally at 0, 8 and 16 hours after operation (diluted with normal saline to 4 mL/kg) respectively; Sham operation group and sepsis group were injected with the same volume of normal saline. Five rats in each group were sacrificed at 2, 6, 12 and 24 hours after operation, the blood sample was collected, and liver tissues were harvested. The levels of serum procalcitonin (PCT), tumor necrosis factor-α (TNF-α) and interleukin (IL-6, IL-1ß) were measured by enzyme linked immunosorbent assay (ELISA), the pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining, and apoptosis index (AI) was measured by TdT-mediated dUTP nick end labeling (TUNEL) method. RESULTS: The degree of hepatocyte injury in sepsis group increased gradually with time, the apoptotic cells gradually increased, and the AI of liver cells increased to 24 hours; serum levels of PCT, TNF-α, IL-6 and IL-1ß were significantly higher than those in the sham operated group at 2 hours after operation and gradually increased to peak at 12 hours. The injury degree of liver tissue in Xuebijing group and curcumin group was significantly lighter than that in sepsis group, and the number of apoptotic cells were significantly decreased; the AI of hepatocytes and serum levels of PCT, TNF-α, IL-6 and IL-1ß were significantly lower than those of sepsis group from 2 hours [AI: (11.89±1.34)%, (11.56±0.96)% vs. (23.59±2.00)% at 2 hours, (28.95±1.40)%, (30.35±1.20)% vs. (52.05±1.31)% at 24 hours; PCT (µg/L): 1.27±0.18, 1.13±0.19 vs. 2.41±0.21 at 2 hours, 5.07±0.45, 5.09±0.42 vs. 8.68±0.58 at 12 hours; TNF-α (ng/L): 127.93±9.53, 124.73±7.47 vs. 217.28±14.24 at 2 hours, 171.03±8.58, 168.68±6.95 vs. 314.13±14.39 at 12 hours; IL-6 (ng/L): 132.15±9.27, 136.14±8.42 vs. 153.35±12.64 at 2 hours, 211.65±8.52, 213.37±8.96 vs. 298.11±12.35 at 12 hours; IL-1ß (ng/L): 33.59±1.49, 35.05±1.00 vs. 61.84±3.21 at 2 hours; 81.76±2.80, 84.06±3.42 vs. 132.24±2.58 at 12 hours, all P < 0.05]. There was no significant difference in the above indexes between Xuebijing group and curcumin group. CONCLUSIONS: Curcumin can inhibit the inflammatory response of hepatocytes in sepsis rats and reduce the apoptosis of hepatocytes, which can protect hepatocytes from sepsis.

[The dose-dependent protective effect of curcumin on hepatocyte of rats with sepsis].

Objective: To observe the protective effect of different doses of curcumin on hepatocytes of rats with sepsis. Methods: 100 healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, and low, medium, high dose curcumin intervention groups (L-cur, M-cur, H-cur groups), with 20 rats in each group. The animal model of sepsis was reproduced by cecal ligation and puncture (CLP) method, and in the sham operation group the cecum was just taken out and returned. In the L-cur, M-cur, H-cur groups curcumin was immediately injected after CLP with a dose of 50, 100, 150 mg/kg, respectively, and the rats in sham operation group and sepsis group were given the same amount of normal saline. Five rats in each group were sacrificed at 2, 6, 12, 24 hours after operation, and the hepatic tissues and blood samples were obtained. The pathological changes in hepatic tissues were observed under a microscope, and hepatocytes apoptosis and apoptosis index (AI) of hepatocytes were determined with transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method, and the levels of serum procalcitonin (PCT), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were determined with enzyme linked immunosorbent assay (ELISA) method. Results: Microscopic examination showed that the damage degree of hepatic tissues was significantly increased in sepsis group; the number of apoptotic cells and damage degree of hepatic tissues were increased gradually over time. The damage degree of hepatic tissues in curcumin groups was lessened as compared with sepsis group, especially in M-cur group. There were no significant changes in AI and serum PCT, TNF-α, and IL-1ß levels at any of the time points tested in the sham operation group. The AI, serum PCT, TNF-α, and IL-1ß levels in the sepsis group were significantly higher than those in the sham operation group from 2 hours after operation on [AI: (23.59±2.00)% vs. (2.02±0.13)%, PCT (µg/L): 2.41±0.21 vs. 0.81±0.01, TNF-α (ng/L): 217.28±14.24 vs. 80.02±2.26, IL-1ß (ng/L): 61.84±3.21 vs. 25.78±1.29, all P < 0.05], and they showed a gradually increasing tendency. AI reached peak value at 24 hours after operation [(52.05±1.31)%]; PCT, TNF-α and IL-1ß reached the peak values at 12 hours after operation [(8.68±0.58) µg/L, (314.13±14.39) ng/L, (132.24±2.58) ng/L, respectively]. Curcumin intervention significantly reduced the levels of AI, TNF-α, PCT and IL-1ß in hepatocytes of septic rats, especially in M-cur group [AI: (11.56±0.96)% vs. (23.59±2.00)% at 2 hours, (30.35±1.20)% vs. (52.05±1.31)% at 24 hours; PCT (µg/L): 1.13±0.19 vs. 2.41±0.21 at 2 hours, 5.09±0.42 vs. 8.68±0.58 at 12 hours; TNF-α (ng/L): 124.73±7.47 vs. 217.28±14.24 at 2 hours, 168.68±6.95 vs. 314.13±14.39 at 12 hours; IL-1ß (ng/L): 35.05±1.00 vs. 61.84±3.21 at 2 hours, 84.06±3.42 vs. 132.24±2.58 at 12 hours; all P < 0.05]. Conclusions: Curcumin can inhibit the inflammatory reaction of hepatocytes of rats, prevent apoptosis, and protect the hepatocytes of rats with sepsis. The concentration of curcumin with the most significant effect is 100 mg/kg, which is the medium dosage.