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Experimental and Therapeutic Medicine Sep 2023Tetracaine hydrochloride (TTC) is a long-lasting local anesthetic commonly used for topical anesthesia. Inappropriate dosage or allergic reactions to TTC can lead to...
Tetracaine hydrochloride (TTC) is a long-lasting local anesthetic commonly used for topical anesthesia. Inappropriate dosage or allergic reactions to TTC can lead to local anesthetic toxicity. TTC exerts cytotoxic effects on certain cell types by inducing apoptosis and necrosis; however, the effects of TTC on macrophages are currently unclear. In the present study, the RAW 264.7 and BV2 cell lines, and murine peritoneal macrophages, were used to evaluate the cytotoxicity of TTC. The present study demonstrated that TTC caused a decrease in cell viability according to a Cell Counting Kit-8 assay, increased lactate dehydrogenase and IL-1β secretion according to ELISA, and induced morphological changes characteristic of pyroptosis according to western blotting. Moreover, TTC-induced macrophage pyroptosis was mediated by gasdermin (GSDM)D, and the cleavage of GSDMD was modulated by both caspase-1 and caspase-11. These results were experimentally validated using caspase-1 and caspase-11 inhibitors. Furthermore, it was observed that TTC and lipopolysaccharide (LPS) exerted similar effects on macrophages. However, the mechanism of induction of pyroptosis by TTC was different from that of LPS. The present study demonstrated that TTC alone could induce macrophage pyroptosis mediated by canonical and non-canonical inflammatory caspases. Therapies targeting pyroptosis may potentially provide a promising future strategy for the prevention and treatment of local anesthetic toxicity induced by TTC.
PubMed: 37602302
DOI: 10.3892/etm.2023.12127 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Jun 2023Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to...
OBJECTIVES
Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism.
METHODS
Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting.
RESULTS
Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1β and IL-18] (all <0.05) but not pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α (TNF-α) in septic mice (all >0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all <0.05). Ozonated triglyceride significantly suppressed the canonical and non-canonical activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (all <0.05) but not affected absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes in vitro (all >0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD.
CONCLUSIONS
Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.
Topics: Animals; Humans; Mice; Caspase 1; Cytokines; Disease Models, Animal; Inflammasomes; Lung Injury; NLR Family, Pyrin Domain-Containing 3 Protein; Ozone; Sepsis
PubMed: 37587065
DOI: 10.11817/j.issn.1672-7347.2023.220634 -
Frontiers in Pharmacology 2023Apolipoprotein A-I (apoA-I), 90% of which is present in high-density lipoprotein (HDL), is the main constituent of HDL, has anti-inflammatory and anti-oxidant...
Apolipoprotein A-I (apoA-I), 90% of which is present in high-density lipoprotein (HDL), is the main constituent of HDL, has anti-inflammatory and anti-oxidant properties, and has received extensive attention in anti-atherosclerosis. Yet little is known about apoA-I 's role in peritoneal dialysis. In this study, by analyzing PD patients ( = 81), we found that decreased apoA/HDL-C ratio is significantly associated with rapid decline in peritoneal function. Further studies were performed in animal experiments to determine the ascendancy of apolipoprotein A-I mimetic peptide (D-4F) on peritoneum, we found that D-4F administration reduced peritoneal fibrosis and peritoneal endothelial mesenchymal transformation (EMT) induced by high glucose peritoneal dialysate, such as N-cadherin, Fibronectin, Vimentin, and α-smooth muscle actin (α-SMA) expression decreased. In mechanism, D-4F can significantly inhibit Smad2/3 phosphorylation, which is the major pathway leading to fibrosis. Furthermore, D-4F treatment inhibited NADPH oxidase and thiobarbituric acid reactive substances (TBARS) expression, increased the activity of certain enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Finally, treatment with D-4F inhibits the expression of interleukins-6(IL-6), Interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Taken together, based on the above research evidence, apoA-I and its peptide mimic may regulate the oxidative stress, TGF- β1/Smads signaling pathway and inflammatory response to reduce peritoneal fibrosis due to peritoneal dialysis.
PubMed: 37576813
DOI: 10.3389/fphar.2023.1106339 -
World Journal of Pediatric Surgery 2023The aim of this study was to identify the state of surgical treatment of neonatal necrotizing enterocolitis (NEC) in China.
OBJECTIVE
The aim of this study was to identify the state of surgical treatment of neonatal necrotizing enterocolitis (NEC) in China.
METHODS
A total of 246 delegates (88.0% senior surgeons) completed a survey sent by the Neonatal Surgery Group of the Pediatric Surgery Branch of the Chinese Medical Association in 2022. Five centers were eliminated due to lack of experience.
RESULTS
Generally, 38.2% of surgeons work in centers where more than 20 cases of surgical NEC are treated per year. A total of 81.3% of surgeons reported the use of ultrasonography; the most used biomarkers were white blood cell count (95.9%), C-reactive protein (93.8%), and procalcitonin (76.3%). Most surgeons (80.9%) used a combination of two (67.2%) antibiotics or single (29.5%) antibiotic for a treatment period of 7-14 days, and most used antibiotics were carbapenems (73.9%), penicillin and cephalosporins (56.0%). Patients are issued the fasting order for 5-7 days by nearly half surgeons (49.8%) for conservative treatment. 70.1% of surgeons deemed that the most difficult decision was to evaluate the optimal timing of surgery. Most surgeons (76.3%) performed diagnostic aspiration of peritoneal fluid. Laparoscopy was performed for the diagnosis and/or treatment of NEC by 40.2% of surgeons. A total of 53.5% of surgeons reported being able to identify localized intestinal necrosis preoperatively. Surgeons relied the most on pneumoperitoneum (94.2%) and failure of conservative treatment (88.8%) to evaluate the surgical indications. At laparotomy, surgical treatments vary according to NEC severity. Infants are fasted for 5-7 days by 55.2% of surgeons postoperatively. Most surgeons (91.7%) followed up with patients with NEC after discharge for up to 5 years (53.8%).
CONCLUSIONS
The most difficult aspect of surgical NEC is evaluating the timing of surgery, and surgeons in the children's specialized hospitals are experienced. The treatment of NEC totalis is controversial, and the indications for laparoscopy need to be further clarified. More multicenter prospective studies are needed to develop surgical guidelines in the future.
PubMed: 37575368
DOI: 10.1136/wjps-2023-000588 -
Cureus Jul 2023Perforation peritonitis is one of the most common emergency presentations in Indian hospitals. Stercoral perforations are rare due to increased intraluminal pressure on...
Perforation peritonitis is one of the most common emergency presentations in Indian hospitals. Stercoral perforations are rare due to increased intraluminal pressure on the gut wall from impacted feces. This is associated with transmural necrosis. We present a 31-year-old pregnant woman who reported abdominal pain and vomiting at 34 weeks of gestation. The diagnosis was unclear from examination and imaging studies, and a provisional diagnosis of acute appendicitis was made. The patient underwent laparotomy and was found to have fecal contamination and multiple stercoral ileal perforations. The bowel segment was resected and exteriorized as a stoma.
PubMed: 37551234
DOI: 10.7759/cureus.41529 -
Archives of Iranian Medicine Feb 2023We aimed to determine the effects of systemic therapy with autologous adipose tissue derived mesenchymal stem cells (AD-MSCs) on different parameters of peritoneal...
BACKGROUND
We aimed to determine the effects of systemic therapy with autologous adipose tissue derived mesenchymal stem cells (AD-MSCs) on different parameters of peritoneal function and inflammation in peritoneal dialysis (PD) patients.
METHODS
We enrolled nine PD patients with ultrafiltration failure (UFF). Patients received 1.2±0.1×10 cell/kg of AD-MSCs via cubital vein and were then followed for six months at time points of baseline, 3, 6, 12, 16 and 24 weeks after infusion. UNI-PET was performed for assessment of peritoneal characteristics at baseline and weeks 12 and 24. Systemic and peritoneal levels of tumor necrosis factor α (TNF-α), , IL-2 and CA125 (by ELISA) and gene expression levels of transforming growth factor beta (TGF-β), smooth muscle actin (𝛼-SMA) and fibroblast-specific protein-1 (FSP-1) in PD effluent derived cells (by quantitative real-time PCR) were measured at baseline and weeks 3, 6, 12, 16 and 24.
RESULTS
Slight improvement was observed in the following UF capacity indices: free water transport (FWT, 32%), ultrafiltration - small pore (UFSP, 18%), ultrafiltration total (UFT, 25%), osmotic conductance to glucose (OCG, 25%), D/P creatinine (0.75 to 0.70), and Dt/D0 glucose (0.23 to 0.26). There was a slight increase in systemic and peritoneal levels of CA125 and a slight decrease in gene expression levels of TGF-β, α-SMA and FSP-1 that was more prominent at week 12 and vanished by the end of the study.
CONCLUSION
Our results for the first time showed the potential of MSCs for treatment of peritoneal damage in a clinical trial. Our results could be regarded as hypothesis suggestion and will need confirmation in future studies.
Topics: Humans; Peritoneal Fibrosis; Pilot Projects; Dialysis Solutions; Transforming Growth Factor beta; Glucose
PubMed: 37543930
DOI: 10.34172/aim.2023.16 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Aug 2023To summarize and analyze the clinical characteristics of patients diagnosed with hepatic portal venous gas (HPVG). (Observational Study)
Observational Study
OBJECTIVE
To summarize and analyze the clinical characteristics of patients diagnosed with hepatic portal venous gas (HPVG).
METHODS
This was a single center retrospective observational study. All of the patients were diagnosed with HPVG. The patients were admitted to Peking University Third Hospital from January 2017 to January 2021. Demographic characteristics, clinical manifestations, laboratory tests, abdominal imaging, treatment of the primary disease, and clinical outcomes of the patients were collected via electronic medical records. The study was approved by institutional review board and the information of all the patients was kept de-identified.
RESULTS
A total of seven cases were included in the study. The median age of the patients was 67 (63, 81) years. Six of the patients were male. The seven patients all presented with sudden onset of severe abdominal pain, which was the most common symptom. Six patients developed septic shock after admission. The signs of HPVG were detected by CT scans in all the patients, showing gas embolization. It might also be found as unique "aquarium sign" in abdominal ultrosonography. Four cases were caused by intestinal lesions, including acute volvulus, intestinal obstruction, and rectal abscess. Two were caused by ischemic bowel disease and the other one was caused by severe acute pancreatitis. The gas accumulation could disappear after effective anti-shock therapy and surgery (Cases 1, 2, and 6). Two patients had good postoperative outcomes, and one patient was discharged after non-surgical treatment. However, the prognosis was poor in the patients with intestinal ischemia necrosis accompanied by shock and multiple organ dysfunction (Cases 3, 4, 5, and 7 all died).
CONCLUSION
The HPVG patients generally have acute abdominal pain and show up at Emergency Department. The prognosis depends on the potential cause of HPVG. The mechanism and clinical management for the appearance of gas in the portal vein is not well understood. Patients complicated with shock, ascites, and peritonitis may have intestinal necrosis, which indicates surgical intervention and higher mortality. CT is the preferred diagnostic method in standard clinical practice. Physicians need to have a comprehensive understanding of the proactive diagnostic strategy, and active treatment for the primary disease.
Topics: Humans; Male; Female; Acute Disease; Pancreatitis; Portal Vein; Vascular Diseases; Necrosis; Abdominal Pain
PubMed: 37534661
DOI: 10.19723/j.issn.1671-167X.2023.04.028 -
Immunity & Ageing : I & A Jul 2023More and more evidences are proving that microglia play a crucial role in the pathogenesis of Alzheimer's disease (AD) and the plasma Aβ levels significantly increased...
More and more evidences are proving that microglia play a crucial role in the pathogenesis of Alzheimer's disease (AD) and the plasma Aβ levels significantly increased 15 years before the onset of dominantly inherited AD. However, the effects of high plasma levels of Aβ on mononuclear macrophage, the peripheral counterparts of microglia, remain unclear. In the present study, we used APP/PS1 transgenic (Tg) mice and a parabiotic model of wild type (Wt) mice and Tg mice (Parabiotic Wt-Tg, Pa (Wt-Tg)) to investigate the effects of high plasma levels of Aβ on peripheral mononuclear macrophage. Our results showed that in the early stage of Tg mice (7 months) and Pa (Wt-Tg) mice (4 months), the proportions of pro-inflammatory macrophages in peritoneal cavity, myeloid derived suppressor cells (MDSCs) in spleen, granulocyte-monocyte progenitors (GMPs) in bone marrow, and the plasma levels of interleukin-6 (IL-6) were significantly decreased. While the proportions of pro-inflammatory macrophages, MDSCs, GMPs, and the plasma levels of IL-6 and tumor necrosis factor (TNF)-α, as well as the numbers of bone marrow-derived macrophages (BMDMs) in mice brain were increased in the late stage of Tg mice (11 months) and Pa (Wt-Tg) mice (8 months). In addition, the proportions of monocytes in spleen and the proliferation of bone marrow cells (BMCs) were enhanced consistently, and the phagocytic function of macrophages kept stably after high plasma levels of Aβ sustaining stimulation. These results demonstrated that high plasma levels of Aβ play a biphasic regulating role at different stages of the disease, namely inhibiting effects on peripheral pro-inflammatory macrophages in the early stage of AD model, while promoting effects in the late stage of AD model. The mechanism behind this may be associated with their effects on MDSCs in spleen and myeloid progenitor cells in bone marrow. Therefore, intervening the effects of plasma Aβ on pro-inflammatory macrophages might offer a new therapeutic approach to AD.
PubMed: 37525137
DOI: 10.1186/s12979-023-00366-4