-
Drug Design, Development and Therapy 2022This study aimed to elucidate the potential molecular mechanisms by which GSRd improves cardiac inflammation and immune environment after MI.
PURPOSE
This study aimed to elucidate the potential molecular mechanisms by which GSRd improves cardiac inflammation and immune environment after MI.
MATERIALS AND METHODS
The potential target genes of GSRd were predicted using the STITCH database. In vivo, MI mice models were established by left anterior descending ligation and were divided into the sham group, MI + Vehicle group, and MI + GSRd group. DMSO, DMSO, and GSRd 50 μL/day were intraperitoneally injected, respectively. After 28 days, echocardiography, Masson staining, immunofluorescence staining, flow cytometry, RT-PCR, and Western blot were performed. Mice peritoneal macrophages were extracted in vitro, and Western blot was performed after GSRd and/or Akt inhibitor MK2206 intervention.
RESULTS
GSRd significantly improved mouse myocardial function, attenuated cardiac fibrosis, and inhibited inflammation and apoptosis in myocardial tissues after myocardial infarction. Meanwhile, GSRd increased non-classical Ly6C Mos/Mps while reduced of classical Ly6C Mos/Mps at the same time in myocardial tissues. In addition, GSRd significantly reversed the activity of p-Akt and p-mTOR in the heart Mos/Mps after MI. In vitro studies showed that the activity of p-Akt and p-mTOR in peritoneal macrophages were significantly increased in a dose-dependent manner after GSRd treatment. Furthermore, the AKT inhibitor MK2206 was found to block the enhanced activity of p-Akt and p-mTOR induced by GSRd in peritoneal macrophages.
CONCLUSION
GSRd can enhance the transformation of Ly6C Mos/Mps to Ly6C Mos/Mps in mice after MI by activating the Akt/mTOR signaling pathway, inhibiting cardiac dysfunction and promoting cardiac repair.
Topics: Animals; Dimethyl Sulfoxide; Ginsenosides; Inflammation; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Monocytes; Myocardial Infarction; Myocardium; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases
PubMed: 36033133
DOI: 10.2147/DDDT.S377624 -
Trauma Case Reports Feb 2022Gastric perforation with necrosis is rare following acute gastric dilation (AGD) and can be fatal. We present a case of a patient with AGD due to a binge-eating episode...
INTRODUCTION
Gastric perforation with necrosis is rare following acute gastric dilation (AGD) and can be fatal. We present a case of a patient with AGD due to a binge-eating episode who left the emergency department (ED) against medical advice (AMA) only to return with gastric perforation and necrosis requiring total splenectomy and partial gastrectomy.
CASE
A 28-year-old female without a remarkable past medical history presented to the ED with diffuse abdominal pain and obstipation after a three-day "food crawl." On admission, a computerized tomography (CT) scan revealed a markedly dilated stomach from the diaphragm to the pelvis with severe mass effect. The therapeutic plan at the time was gastric decompression via a nasogastric tube. The following day, the patient reported feeling better and left AMA only to return the same evening with worsening symptoms and peritoneal signs. The patient was then emergently taken to the operating room (OR). In the OR, laparotomy revealed frank spillage of partially digested food and necrosis along the greater curvature of the stomach that extended to the spleen. Damage control surgery was performed, which required a total splenectomy and a partial gastrectomy. The patient was admitted to the intensive care unit (ICU) and subsequently underwent five more trips to the OR due to severe edema that delayed the primary closure of the fascia. Once the patient was transferred out of the ICU, she was evaluated by psychiatry and diagnosed with a binge-eating disorder.
CONCLUSION
This case demonstrates the severity of acute gastric dilation and its potentially lethal consequences. In some cases, such as this one, the patient may present with mild symptoms and not comprehend the gravity of the situation. Therefore, it is important for clinicians to recognize this condition as a true emergency and perform immediate decompression and evaluation for surgery.
PubMed: 35024408
DOI: 10.1016/j.tcr.2021.100598 -
Biological & Pharmaceutical Bulletin 2023A methanol extract of rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) showed hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide...
A methanol extract of rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) showed hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. We had previously isolated 46 compounds, including several types of iridoid glycosides, phenylethanoid glycosides, and aromatics, etc., from the extract. Among them, picroside II, androsin, and 4-hydroxy-3-methoxyacetophenone exhibited active hepatoprotective effects at doses of 50-100 mg/kg, per os (p.o.) To characterize the mechanisms of action of these isolates and to clarify the structural requirements of phenylethanoid glycosides for their hepatoprotective effects, their effects were assessed in in vitro studies on (i) D-GalN-induced cytotoxicity in mouse primary hepatocytes, (ii) LPS-induced nitric oxide (NO) production in mouse peritoneal macrophages, and (iii) tumor necrosis factor-α (TNF-α)-induced cytotoxicity in L929 cells. These isolates decreased the cytotoxicity caused by D-GalN without inhibiting LPS-induced macrophage activation and also reduced the sensitivity of hepatocytes to TNF-α. In addition, the structural requirements of phenylethanoids for the protective effects of D-GalN-induced cytotoxicity in mouse primary hepatocytes were evaluated.
Topics: Mice; Animals; Rhizome; Picrorhiza; Lipopolysaccharides; Tumor Necrosis Factor-alpha; Iridoid Glycosides; Plant Extracts; Galactosamine
PubMed: 37258151
DOI: 10.1248/bpb.b23-00167 -
The Journal of Veterinary Medical... Apr 2020In camels, hepatic diseases are relatively common and most of them are misdiagnosed as a cause of illness because signs may be subtle. In addition, diagnostic laboratory... (Review)
Review
In camels, hepatic diseases are relatively common and most of them are misdiagnosed as a cause of illness because signs may be subtle. In addition, diagnostic laboratory methods are insufficient as hepatic enzymes can also be elevated in camels with cardiac or skeletal muscle damage. Examples of liver diseases in camels are hepatic lipidosis, hepatitis, cirrhosis, hepatic necrosis, choleostasis, hyperplasia of biliary epithelium, hydatid cysts, glycogen deposition, cholangitis, cholangiohepatitis, calcified hydatid cyst and hepatic abscesses. When the liver is examined by ultrasonography, the clinician gets sufficient information about the size, position, echopatterns of the hepatic parenchyma, bile ducts and outlines of the hepatic blood vessels. Ultrasonography has been used previously in camels only for reproductive purposes. However, during the past decade, it has been used for scanning of the healthy organs as well as evaluation and determining the diagnosis and prognosis of non-reproductive disorders. Examples of diseases evaluated by ultrasonography in camels are paratuberculosis, trypanosomiasis, abdominal and urinary disorders, thoracic diseases, renal tumors, pyelonephritis, renal abscessation, gastrointestinal tumors, chronic peritonitis and splenic abscessation. Ultrasound-guidance in biopsy of hepatic lesions and in portocentesis has also been reported in camels. This mini review article is written to shed light on ultrasonography of the liver and its blood vessels in healthy camels as well as finding in camels with hepatic disorders such as fatty infiltration of the liver, hepatic abscesses and calcification of the bile ducts.
Topics: Animals; Bile Ducts; Camelus; Liver; Liver Diseases; Ultrasonography
PubMed: 32101826
DOI: 10.1292/jvms.19-0690 -
Kidney Diseases (Basel, Switzerland) Jan 2020We have hypothesized that the problem of dyslipidemia in peritoneal dialysis (PD) patients lies beyond certain levels of plasma lipoprotein and involves cardiovascular...
BACKGROUND
We have hypothesized that the problem of dyslipidemia in peritoneal dialysis (PD) patients lies beyond certain levels of plasma lipoprotein and involves cardiovascular risk, but can also influence the development of chronic intraperitoneal inflammation.
OBJECTIVES
The aim of our work was to define whether the association of dyslipidemia with intraperitoneal inflammation really exists and if it could it be used in a prospective cohort of PD patients.
PATIENTS AND METHODS
We performed a cross-sectional, single-center, pilot study involving 40 nondiabetic PD patients (27 men and 13 women with an average age of 49.3 ± 12.2 years). The median time on PD was 29 (18.5-37) months. The parameters dialysis adequacy, blood lipid profile, and the concentrations of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-10 in peritoneal dialysate effluent (PDE) were determined. Cohen's effect size was computed post hoc to determine the differences between groups in the concentrations of pro- and anti-inflammatory mediators.
RESULTS
PD patients with atherogenic dyslipidemia had significantly high levels of MCP-1 compared with dyslipidemia-free patients (Cohen's = 1.32). A reduced high-density lipoprotein cholesterol level was associated with a high intraperitoneal production of the proinflammatory mediator TNF-α ( < 0.0001) and anti-inflammatory IL-10 ( < 0.0001). Atherogenic index of plasma was directly correlated with MCP-1 ( < 0.0001) and TNF-α ( < 0.0001). In multiple regression analysis, MCP-1 appeared to predict PD inadequacy ( = 0.58; ratio = 9.4; = 0.006) independently of age and blood C-reactive protein level. Effect size was 1.38 with α = 0.05, = 40, and 3 predictors.
CONCLUSIONS
Our cross-sectional pilot study first demonstrated a close interaction between the atherogenic lipid profile and a high concentration of MCP-1 in PDE; this might be a prognostic marker for PD inadequacy. The potential significance of our finding is that it provides useful preliminary information necessary for further research into this area.
PubMed: 32021872
DOI: 10.1159/000503632 -
Journal of Clinical Medicine Apr 2024: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor family involved in processes in many inflammatory states. OPG concentration is enhanced in the...
: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor family involved in processes in many inflammatory states. OPG concentration is enhanced in the majority of chronic kidney disease (CKD) patients and those undergoing renal replacement therapy. The aim of the study was to assess the relation of OPG and chronic inflammation in peritoneal dialysis (PD) patients and to evaluate whether OPG concentrations in plasma and dialysate were related to plasma and dialysate levels of proinflammatory mediators (interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), interleukin 33 (IL-33) and interleukin 1 receptor-like 1IL-1RL1 (IL-1RL1, sST2)). : The study included 37 patients of the Peritoneal Dialysis Center, Department of Nephrology, Transplantology and Internal Medicine, Szczecin, Poland, 4-6 weeks after the onset of peritoneal dialysis therapy. During a peritoneal equilibration test, plasma (at 2 h) and dialysate (at 4 h) OPG, IL-33, 1IL-1RL1 (sST2), IL-6 and hsCRP concentrations were determined. : Plasma concentration of OPG did not correlate with dialysate OPG level ( = 0.04, = 0.8). There was a strong positive correlation between plasma OPG concentrations and plasma IL-1RL1 (sST2) ( = 0.41; = 0.01), plasma IL-6 ( = 0.38; = 0.01) and plasma hsCRP ( = 0.35; = 0.02). Dialysate OPG concentrations were positively associated with dialysate IL-1RL1 (sST2) ( = 0.37; = 0.02) and dialysate IL-6 levels ( = 0.44; = 0.005). Multivariate analysis showed that higher IL-1RL1 (sST2) ( = +0.38, = 0.006), higher plasma hsCRP ( = +0.32, = 0.02) and older age ( = +0.35, = 0.01) were independent determinants of higher plasma OPG concentration and that higher concentrations of dialysate IL-6 ( = +0.37, = 0.02) were independent determinants of higher dialysate OPG concentration. : Both plasma and dialysate OPG levels are associated with the severity of systemic and local inflammation illustrated by the plasma and dialysate concentrations of IL-1RL1 (sST2), hsCRP and IL-6, suggesting that OPG might have a pivotal role in explaining the milieu of systemic and intraperitoneal inflammation.
PubMed: 38673616
DOI: 10.3390/jcm13082345 -
Iranian Journal of Allergy, Asthma, and... Dec 2020The presence of ambient particulate matter (PM) poses more dangers to human health than that of other common air pollutants such as Carbon dioxide (Co2) and ozone. ...
The presence of ambient particulate matter (PM) poses more dangers to human health than that of other common air pollutants such as Carbon dioxide (Co2) and ozone. Epidemiologic studies show a direct correlation between PM and the risk of respiratory and cardiovascular diseases. The immune system seems to play a critical role in the process of these diseases. The main goal of this study was to investigate the effect of Tehran particulate matter in two aerodynamic diameters (PM2.5 and PM10) on alveolar macrophages (AM) from C57/BL6 mice. To evaluate the inflammatory effects of PMs, cultured alveolar, and peritoneal macrophages were treated with PM2.5 and PM10 (concentrations of 5 µg/mL and 10 µg/mL). Tumor necrosis factor-alpha (TNF-α) and IL-10 (representatives of inflammatory and anti-inflammatory cytokines, respectively) were assessed in the culture supernatant by ELISA. Expression of arginase and inducible nitric oxide synthase (iNOS) genes was carried out by quantitative real-time PCR. Different functional types of cultured alveolar macrophages (M1, M2) were also determined in this study. Our results suggest that PM2.5 induces M1 inflammatory phenotype in comparison with PM10. We found Also, an increase in TNF-α and M1-related gene expression (iNOS), as well as a decrease in both IL-10 and M2 phenotype genes (Arginase). Moreover, a reduction in phagocytic capacity and increased apoptosis function of macrophage cells were detected. PM2.5 as a major component in hydrocarbons has a considerable effect on polarizing the alveolar macrophages to an inflammatory phenotype and eliciting lung inflammation in mice.
Topics: Air Pollutants; Animals; Apoptosis; Arginase; Cytokines; Gene Expression; Inflammation; Interleukin-10; Macrophages, Alveolar; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II; Particulate Matter; Phagocytes; Phenotype; Tumor Necrosis Factor-alpha
PubMed: 33463134
DOI: 10.18502/ijaai.v19i6.4934 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Dec 2022To investigate the mechanism by which the small molecule compound WP1130 inhibits NLRP3 inflammasome activation and alleviates septic shock.
OBJECTIVE
To investigate the mechanism by which the small molecule compound WP1130 inhibits NLRP3 inflammasome activation and alleviates septic shock.
METHODS
Mouse bone marrow-derived macrophages (BMDM) and human THP-1 cells were pre-treated with WP1130 before stimulation with different NLRP3 inflammasome agonists (Nigericin, ATP, MSU and intracellular LPS transfection), and AIM2 inflammasomes were activated with poly A: T. The levels of caspase-1 and IL-1β in the cell culture supernatant were determined using Western blotting and ELISA, and mitochondrial damage in the cells was observed using confocal microscopy. In the animal experiment, male C57BL/6 mice were randomized into blank control group, septic shock group (LPS group) and WP1130 treatment group (WP1130+LPS group), and the levels of IL-1β and TNF-α in the serum and peritoneal cavity were detected using ELISA.
RESULTS
In murine BMDM and human THP-1 cells, WP1130 significantly inhibited NLRP3 agonists-induced caspase-1 and IL-1β secretion in a dose-dependent manner ( < 0.05) but did not obviously affect the secretion of such inflammatory factors as IL-6 and TNF-α that were not associated with inflammasomes (>0.05). Treatment with WP1130 did not significantly affect poly A: T-induced activation of AIM2 inflammasomes (>0.05) or induce obvious changes in mitochondrial damage, an upstream signal of NLRP3 inflammasome activation. In the mouse model of LPS-induced septic shock, WP1130 treatment significantly reduced the level of IL-1β ( < 0.05) without obviously affecting TNF-α level either in the serum or in the peritoneal cavity (>0.05).
CONCLUSION
WP1130 specifically inhibits NLRP3 inflammasome activation to alleviate LPS-induced septic shock in mice.
Topics: Male; Humans; Animals; Mice; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Shock, Septic; Tumor Necrosis Factor-alpha; Lipopolysaccharides; Mice, Inbred C57BL; Caspase 1; Interleukin-1beta
PubMed: 36651241
DOI: 10.12122/j.issn.1673-4254.2022.12.01 -
Radiology Case Reports Oct 2022Gynecological malignancies including primary cervical cancers are frequently treated with chemotherapy and radiation. Fistulas affecting the gynecological organs and...
Gynecological malignancies including primary cervical cancers are frequently treated with chemotherapy and radiation. Fistulas affecting the gynecological organs and surrounding cavities are a known consequence of radiotherapy due to focal necrosis of the regional mucosa. In this report, we will demonstrate a rare case of a posterior vaginal wall rupture with resulting fistulization into the peritoneal cavity in a 50-year-old female patient with squamous cell carcinoma of the cervix status postchemoradiotherapy. Magnetic resonance imaging (MRI) showed a discontinuity in the posterior vaginal wall near the fornix with extravasation of ultrasound gel used as contrast into the intraperitoneal compartment. Patient later presented with peritonitis like signs and symptoms and was treated successfully with antibiotics. Vaginal gel should be used with caution in patients with prior history of radiation due to the possibility of vaginal rupture which may lead to peritoneal vaginal fistula and contrast extravasation.
PubMed: 35965925
DOI: 10.1016/j.radcr.2022.06.083 -
Acta Pharmacologica Sinica May 2022Monosodium urate (MSU) crystals, the etiological agent of gout, are formed in joints and periarticular tissues due to long-lasting hyperuricemia. Although MSU...
Monosodium urate (MSU) crystals, the etiological agent of gout, are formed in joints and periarticular tissues due to long-lasting hyperuricemia. Although MSU crystal-triggered NLRP3 inflammasome activation and interleukin 1β (IL-1β) release are known to have key roles in gouty arthritis, recent studies revealed that MSU crystal-induced necrosis also plays a critical role in this process. However, it remains unknown what forms of necrosis have been induced and whether combined cell death inhibitors can block such necrosis. Here, we showed that MSU crystal-induced necrosis in murine macrophages was not dependent on NLRP3 inflammasome activation, as neither genetic deletion nor pharmacological blockade of the NLRP3 pathway inhibited the necrosis. Although many cell death pathways (such as ferroptosis and pyroptosis) inhibitors or reactive oxygen species inhibitors did not have any suppressive effects, necroptosis pathway inhibitors GSK'872 (RIPK3 inhibitor), and GW806742X (MLKL inhibitor) dose-dependently inhibited MSU crystal-induced necrosis. Moreover, a triple combination of GSK'872, GW806742X, and IDN-6556 (pan-caspase inhibitor) displayed enhanced inhibition of the necrosis, which was further fortified by the addition of MCC950 (NLRP3 inhibitor), suggesting that multiple cell death pathways might have been triggered by MSU crystals. Baicalin, a previously identified inhibitor of NLRP3, inhibited MSU crystal-induced inflammasome activation and suppressed the necrosis in macrophages. Besides, baicalin gavage significantly ameliorated MSU crystal-induced peritonitis in mice. Altogether, our data indicate that MSU crystals induce NLRP3-independent necrosis, which can be inhibited by combined inhibitors for multiple signaling pathways, highlighting a new avenue for the treatment of gouty arthritis.
Topics: Animals; Arthritis, Gouty; Gout; Inflammasomes; Interleukin-1beta; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Necrosis; Signal Transduction; Uric Acid
PubMed: 34376811
DOI: 10.1038/s41401-021-00749-7