Plac8-ERK pathway modulation of monocyte function in sepsis.

Sepsis, a life-threatening condition caused by infection, is characterized by the dysregulation of immune responses and activation of monocytes. Plac8, a protein, has been implicated in various inflammatory conditions. This study aimed to investigate the effect of Plac8 upregulation on monocyte proliferation and activation in sepsis patients. Peripheral blood samples were collected from healthy individuals and sepsis patients. Monocytes were stimulated with lipopolysaccharide (LPS) to create an in vitro sepsis model, while a murine sepsis model was established using cecal ligation and puncture (CLP). The levels of monocyte markers, proliferation index (PI), and pro-inflammatory cytokines were assessed using flow cytometry and qPCR, respectively. Plac8 and phosphorylated ERK protein levels were determined by western blot, and TNF-α, IL-6, and IL-10 levels were quantified using ELISA. The CCK-8 assay was used to evaluate PBMC proliferation and activation. The results showed that Plac8 was highly expressed in sepsis models, promoting the survival, proliferation, and activation of monocytes. Plac8 upregulation activated the ERK pathway, leading to increased phosphorylation of ERK protein and elevated levels of CD14, CD16, TNF-α, IL-6, Plac8, and IL-10. In sepsis mice, Plac8 overexpression similarly activated the ERK pathway and promoted the survival, proliferation, and activation of monocytes. In conclusion, the upregulation of Plac8 enhances the activation of the ERK pathway and promotes monocyte proliferation and activation in sepsis patients.

Genipin Attenuates Sepsis-Induced Splenocyte Apoptosis via the Inhibition of Endoplasmic Reticulum Stress.

Endoplasmic reticulum (ER) dysfunction is characterized by ER stress, which can be triggered by sepsis. Recent studies have reported that lessening ER stress is a promising therapeutic approach to improving the outcome of sepsis. Genipin is derived from gardenia fruit, which is a traditional Chinese medicinal herb for anti-inflammation. Here, mice were treated with genipin (2.5 mg/kg) intravenously to assess its biological effects and underlying mechanism against polymicrobial sepsis. Furthermore, the present study focused on detecting the levels of ER stress-related proteins, including protein kinase R-like ER kinase (PERK), glucose-regulated protein of 78 kDa (GRP78), phosphorylated-eukaryotic initiation factor 2α (p-eIF2α), and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP). The results demonstrated that genipin significantly decreased the serum concentrations of tumor necrosis factor-α and interleukin-6, alleviated histopathological damage to the lungs, livers and spleens, and even improved the survival rates of septic mice. Moreover, sepsis significantly upregulated the protein expression levels of splenic GRP78, PERK, p-eIF2α and CHOP, but their levels were significantly suppressed by genipin. Furthermore, genipin also significantly downregulated cleaved caspase-3 expression levels and reduced sepsis-induced splenocyte apoptosis. In conclusion, genipin potentially improved the survival rate of sepsis and attenuated sepsis-induced organ injury and an excessive inflammatory response in mice. The effects of genipin against sepsis were potentially associated with decreased splenocyte apoptosis via the attenuation of sepsis-induced ER stress to further inhibit ER stress-induced apoptosis.

The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance via Regulation of Monocyte Recruitment and Activity in Polymicrobial Septic Peritonitis.

The cholinergic anti-inflammatory pathway has been identified as an effective pathway to modify inflammatory responses. Here, we verified that delayed administration with a selective α7nAChR agonist GTS-21 enables a more efficient elimination of the offending pathogens, diminished inflammatory response and organ injury, and improved survival rates in the polymicrobial septic peritonitis model. We illustrated that the improved bacterial clearance upon GTS-21 stimulation was accompanied by enhanced recruitment of monocytes into the peritoneal cavity and simultaneously increased phagocytic activity and iNOS expression of these recruited monocytes. Mechanically, splenectomy prior to administration of GTS-21 attenuated the recruitment of monocytes into the peritoneal cavity and abolished the protective benefits of GTS-21 treatment. Meanwhile, GTS-21 administration accelerates the deployment of splenic monocytes during septic peritonitis. Collectively, these data suggested that appropriate selective pharmacological α7nAChR activation promotes monocytes trafficking in a spleen-dependent manner and upregulates the antibacterial activity of recruited monocytes during septic peritonitis, which may be utilized as a promising therapeutic modality for patients suffering from septic peritonitis.

Nanocomplexes of curcumin and glycated bovine serum albumin: The formation mechanism and effect of glycation on their physicochemical properties.

Bovine serum albumin (BSA) and BSA-glucose conjugates (GBSAⅠ and GBSAⅠI) with different extent of glycation were complexed with curcumin (CUR). The formation mechanism of BSA/GBSA-CUR complexes and the effect of glycation on their physicochemical properties were investigated. Fluorescence quenching and FTIR analysis indicated that the BSA/GBSA-CUR nanocomplexes were formed mainly by hydrophobic interactions. XRD analysis demonstrated that CUR was present in an amorphous state in the nanocomplexes. BSA with a greater extent of glycation (BSA < GBSAⅠ

Inhibition of ultraviolet-induced sea cucumber (Stichopus japonicus) autolysis by maintaining coelomocyte intracellular calcium homeostasis.

Apoptosis plays a critical role in sea cucumber autolysis. To investigate the ultraviolet (UV)-induced apoptosis, sea cucumbers with and without injection of BAPTA-AM (cytosolic calcium chelator) were exposed to UV (15 W/m2) for 30 min. The results showed that UV irradiation caused several changes in sea cucumber coelomocytes, including calcium imbalance, abnormal morphology of endoplasmic reticulum, upregulation of pro-apoptotic proteins CRT, CHOP, and caspases 9 and 3, and downregulation of anti-apoptotic protein Bcl-2. A comparison between the two groups showed that injection of the calcium chelator into sea cucumbers helped maintain coelomocyte intracellular calcium homeostasis and suppressed other abnormal changes caused by ER stress, indicating apoptosis in sea cucumbers is mediated by calcium imbalance and follows the activation of the ER stress pathway. Therefore, this study broadens understanding of the apoptotic mechanism involved in sea cucumber autolysis, which is helpful in developing preservative agents for sea cucumbers.

Adenosine stress thallium-201 myocardial perfusion imaging for detecting coronary artery disease at an early stage.

The aims of this study were to evaluate the diagnostic value of adenosine thallium-201 myocardial perfusion imaging and to compare it with exercise stress thallium-201 myocardial perfusion imaging for detecting coronary artery disease (CAD) at an early stage. Forty-one patients suspected with CAD were randomly divided into two groups. In Group 1 (n=21) adenosine stress was undertaken; the exercise stress myocardial perfusion imaging was performed in Group 2 (n=20). Coronary angiography (CAG) was performed in each patient within 2 weeks before or after single photon emission computed tomography (SPECT). Adenosine stress group vs. exercise stress group, the sensitivity was 92.86% vs. 100.0%, specificity 57.14% vs. 60.0%, positive predictive value 81.25% vs. 71.43%, negative predictive value 80.0% vs. 100.0%, accuracy 80.95% vs. 80.0% respectively. Detection rates of vessels of coronary artery lesions were 66.67% in Group 1 and 72.22% in Group 2 (P> 0.05). The side effects were mild and transient. Our results demonstrated that adenosine stress myocardial perfusion imaging is a safe and reliable diagnostic method for an early stage of CAD. As a comparative sensitivity and accuracy with exercise stress thallium-201 myocardial perfusion imaging, adenosine stress testing may provide a feasible alternative pharmacological stress method in myocardial SPECT for detection of CAD.

Highly metabolic thrombus of the portal vein: 18F fluorodeoxyglucose positron emission tomography/computer tomography demonstration and clinical significance in hepatocellular carcinoma.

AIM: To assess the ability of (18)F-fluorodeoxyglucose positron emission tomography/computer tomography ((18)F-FDG PET/CT) to differentiate between benign and malignant portal vein thrombosis in hepatocellular carcinoma (HCC) patients. METHODS: Five consecutive patients who had HBV cirrhosis, biopsy-proven HCC, and thrombosis of the main portal vein and/or left/right portal vein on ultrasound (US), computer tomography (CT) or magnetic resonance imaging (MRI) were studied with (18)F-FDG PET/CT. The presence or absence of a highly metabolic thrombus on (18)F-FDG PET/CT was considered diagnostic for malignant or benign portal vein thrombosis, respectively. All patients were followed-up monthly with US, CT or MRI. Shrinkage of the thrombus or recanalization of the vessels on US, CT or MRI during follow-up was considered to be definitive evidence of the benign nature of the thrombosis, whereas enlargement of the thrombus, disruption of the vessel wall, and parenchymal infiltration over follow-up were considered to be consistent with malignancy. (18)F-FDG PET/CT, and US, CT or MRI results were compared. RESULTS: Follow-up (1 to 10 mo) showed signs of malignant thrombosis in 4 of the 5 patients. US, CT or MRI produced a true-positive result for malignancy in 4 of the patients, and a false-positive result in 1. (18)F-FDG PET/CT showed a highly metabolic thrombus in 4 of the 5 patients. (18)F-FDG PET/CT achieved a true-positive result in all 4 of these patients, and a true-negative result in the other patient. No false-positive result was observed using (18)F-FDG PET/CT. CONCLUSION: (18)F-FDG PET/CT may be helpful in discriminating between benign and malignant portal vein thrombi. Patients may benefit from (18)F-FDG PET/CT when portal vein thrombi can not be diagnosed exactly by US, CT or MRI.

Positron emission tomography/computer tomography in guidance of extrahepatic hepatocellular carcinoma metastasis management.

Hepatocellular carcinoma (HCC) is one of the most common primary cancers in the world. Surgery is the gold standard for treatment of patients with HCC. Recurrence and metastasis are the major obstacles to further improve the prognosis of HCC. Most recurrences are intrahepatic. However, 30% of the recurrences are extrahepatic. The role of resection in intrahepatic recurrences is widely accepted. The role of resection in extrahepatic HCC recurrence and metastasis is not well established. 18F fluorodeoxyglucose (18F-FDG) positron emission tomography/computer tomography (PET/CT) is useful in detecting distant metastasis from a variety of malignancies and shows superior accuracy to conventional imaging modalities in identification of intrahepatic and extrahepatic metastasis. We present one patient with one new isolated omental lymph node metastasis, who had a history of huge HCC resected six years ago. The metastatic focus was identified with 18 F-FDG PET/CT and resected. The follow-up revealed good prognosis with a long-term survival potential after resection of the omental lymphatic metastasis.

[Clinical evaluation of eschar grinding and biological dressing A for treatment of deep partial-thickness burn wound on the extremities].

OBJECTIVE: To evaluate the clinical effect of eschar grinding and wound coverage by biological dressing A in the management of deep partial-thickness burn wound on the extremities. METHODS: Seventy-three patients with deep partial-thickness burns on the extremities were divided into two groups to receive different managements. The patients in group 1 were treated with eschar grinding and wound coverage with biological dressing A, and group 2 received conventional treatment. The white blood cell count, body temperature, incidence of wound infection and wound healing time were observed. RESULTS: Compared with conventional treatment, wound management with eschar grinding and coverage by biological dressing A could increase the effective rate (29/32 vs 31/41, P<0.05), inhibit systemic inflammation and scar hypertrophy, and shorten the wound healing time (13.79-/+5.72 vs 17.08-/+8.39, P<0.01). CONCLUSION: Eschar grinding and wound coverage by biological dressing A can be effective for management of deep partial-thickness burns on the extremities, and earlier treatment with the dressing A achieves better effect.