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Arthritis Research & Therapy Jul 2018The findings of a previous study by Jin et al. have shown that microRNA (miR)-155 was upregulated in patients with acute gouty arthritis and enhanced the proinflammatory...
BACKGROUND
The findings of a previous study by Jin et al. have shown that microRNA (miR)-155 was upregulated in patients with acute gouty arthritis and enhanced the proinflammatory cytokines. There is no direct evidence to support that miR-155 is indeed involved in monosodium urate (MSU)-induced inflammatory responses in vivo. The aim of this study was to investigate the role of miR-155 knock-out (KO) or knock-in (KI) mice in MSU-induced animal models to mimic acute gout.
METHODS
MiR-155 expression in cultured bone marrow-derived macrophages (BMDMs) from miR-155 KO, miR-155 KI, and wild-type (WT) mice treated with MSU crystals in vitro was detected by real-time quantitative polymerase chain reaction (qPCR). MiR-155 KO and WT mice were used to induce an acute gouty inflammatory response with MSU crystals including models of foot pad inflammation, ankle arthritis, air pouch inflammation, and peritonitis. Furthermore, the proinflammatory interleukin (IL)-1β levels in lavage fluids from air pouch and peritoneal cavity models were measured by enzyme-linked immunosorbent assay (ELISA), and tumor necrosis factor (TNF)-α production from BMDMs of miR-155 KI mice treated with MSU were measured by flow cytometry.
RESULTS
MiR-155 expression was quickly upregulated in BMDMs from WT mice following MSU treatment in vitro. In comparison with WT mice in vivo, the swelling index of miR-155 KO mice showed no significant difference in the murine foot pad and ankle arthritis models for the indicated different time points. There were similar changes in total cell numbers of lavage fluids in the air pouch and peritoneal cavity models between miR-155 KO and WT mice following MSU crystal injection. Moreover, the IL-1β levels of lavage fluids in the air pouch and peritonitis models from miR-155 KO mice were almost the same as those from WT mice. TNF-α levels were comparable from BMDMs treated with MSU crystals in vitro between miR-155 KI mice and WT mice.
CONCLUSIONS
MiR-155 is dispensable in MSU-induced gouty inflammation in mice. Deletion of miR-155 might not be an effective therapeutic approach to relieve the inflammation in acute gout.
Topics: Animals; Arthritis, Experimental; Arthritis, Gouty; Gene Knock-In Techniques; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Uric Acid
PubMed: 29996893
DOI: 10.1186/s13075-018-1550-y -
Cureus Dec 2021Scrotal necrosis is a rare occurrence that is scarcely reported among patients having undergone heated intra-peritoneal chemotherapy (HIPEC) procedures. Due to anatomic...
Scrotal necrosis is a rare occurrence that is scarcely reported among patients having undergone heated intra-peritoneal chemotherapy (HIPEC) procedures. Due to anatomic factors and the thermally enhanced cytotoxicity of chemotherapeutic agents, this complication can have debilitating post-operative effects. We herein highlight the presentation of scrotal necrosis in a patient who underwent HIPEC procedure for peritoneal metastasis secondary to colorectal carcinoma, and how it contrasts to previously documented cases of a similar nature. Furthermore, we describe a successful management strategy that consisted of conservative measures followed by surgical debridement and primary repair, and enabled the patient to experience significant functional and cosmetic improvement.
PubMed: 34976544
DOI: 10.7759/cureus.20638 -
International Journal of Molecular... Jun 2022Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival,...
Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival, its prognosis remains poor. Established chemotherapeutics include mitomycin C (MMC) and cisplatin (CP), both characterized by severe side effects. GP-2250 is a novel antineoplastic agent, currently under clinical investigation. This in vitro study aims to investigate effects of GP-2250 including combinations with CP and MMC on malignant mesothelioma. JL-1 and MSTO-211H mesothelioma cell lines were treated with increasing doses of GP-2250, CP, MMC and combination therapies of GP-2250 + CP/MMC. Microscopic effects were documented, and a flow-cytometric apoptosis/necrosis assay was performed. Synergistic and antagonistic effects were analyzed by computing the combination index by Chou-Talalay. GP-2250 showed an antiadhesive effect on JL-1 and MSTO-211H spheroids. It had a dose-dependent cytotoxic effect on both monolayer and spheroid cultured cells, inducing apoptosis and necrosis. Combination treatments of GP-2250 with MMC and CP led to significant reductions of the effective doses of CP/MMC. Synergistic and additive effects were observed. GP-2250 showed promising antineoplastic effects on malignant mesothelioma cells in vitro especially in combination with CP/MMC. This forms the basis for further in vivo and clinical investigations in order to broaden treatment options.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Cisplatin; Humans; Mesothelioma; Mesothelioma, Malignant; Mitomycin; Necrosis; Peritoneal Neoplasms
PubMed: 35806313
DOI: 10.3390/ijms23137293 -
BMC Nephrology Apr 2019Mitochondrial DNA (mtDNA) released into extracellular subsequent to cell injury and death can promote inflammation in patients and animal models. However, the effects of...
BACKGROUND
Mitochondrial DNA (mtDNA) released into extracellular subsequent to cell injury and death can promote inflammation in patients and animal models. However, the effects of peritoneal dialysate cell-free mtDNA on intraperitoneal inflammation and peritoneal solute transport rate (PSTR) in peritoneal dialysis (PD) patients remain unclear.
METHODS
We select the incident patients who began PD therapy between January 1, 2009, and December 30, 2010. Peritoneal dialysate was collected at the time of peritoneal equilibration test. The cell-free mtDNA, IL-6, IL-17A, TNF-α and IFN-γ were measured. All patients were followed till December 2017. The results were compared with PSTR and patient survival.
RESULTS
One hundred and eighty-nine patients were included in the study. The average age was 47.1 ± 13.5 years, 55.6% of the patients were males. The average PSTR was 0.66 ± 0.12, the median dialysate mtDNA levels were 4325 copies/ul. The median concentrations of IL-6, IL-17A, TNF-α and IFN-γ were 25.9, 10.8, 25.8 and 17.9 pg/ml, respectively. We found that dialysate mtDNA was significantly correlated with PSTR (r = 0.461, P < 0.001), IL-6 (r = 0.568, P < 0.001), TNF-α (r = 0.454, P < 0.001) and IFN-γ (r = 0.203, P = 0.005). After adjustment for multiple covariates, dialysate mtDNA levels were independently correlated with IL-6 and PSTR. Dialysate mtDNA levels were not associated with patient survival.
CONCLUSIONS
We found that dialysate mtDNA levels correlated with the degree of intraperitoneal inflammatory status in PD patients. Peritoneal effluent mtDNA was an independent determinant of PSTR but did not affect patient survival.
Topics: Adult; Ascitic Fluid; Biomarkers; DNA, Mitochondrial; Dialysis Solutions; Female; Humans; Interleukin-17; Interleukin-6; Kidney Failure, Chronic; Male; Middle Aged; Outcome Assessment, Health Care; Peritoneal Dialysis; Peritonitis; Tumor Necrosis Factors
PubMed: 30975091
DOI: 10.1186/s12882-019-1284-3 -
Experimental Gerontology Jan 2023Malnutrition is considered one of the most common problems in the elderly population worldwide and can significantly interfere in health evolution in these individuals,...
Malnutrition is considered one of the most common problems in the elderly population worldwide and can significantly interfere in health evolution in these individuals, predisposing them to increased infection susceptibility. The immune response triggered by infections comprises several mechanisms, and macrophages play important roles in this response. This study aimed to evaluate mechanisms related to macrophage function in a model of protein malnutrition in the elderly. Two age groups (young: 3-5 months and elderly: 18-19 months) male C57BL/6NTac mice were subjected to protein malnutrition with a low-protein diet (2 %). The nutritional status, hemogram and number of peritoneal cells were affected by both age and nutritional status. Additionally, the spreading capacity as well as the phagocytic and fungicidal activity of peritoneal macrophages were affected by the nutritional status and age of the animal. Interestingly, the percentages of F4/80/CD11b and CD86 cells were reduced mostly in elderly animals, while the TLR-4 population was more affected by nutritional status than by age. The production of pro-inflammatory cytokines such as TNF-α, IL-1α, and IL-6 was also influenced by nutritional status and/or by age, and malnourished animals of advanced age produced higher amounts of the anti-inflammatory cytokine IL-10. Furthermore, the phosphorylation ratio of the transcription factor NFκB (pNFκB/NFκB) was directly affected by the nutritional status, independently of age. Thus, these results allow us to conclude that aging and protein malnutrition compromise macrophage function, likely affecting their immune function, and in aged protein-malnourished animals, this impairment tends to be more pronounced.
Topics: Aged; Humans; Mice; Male; Animals; Macrophages, Peritoneal; Mice, Inbred BALB C; Mice, Inbred C57BL; NF-kappa B; Tumor Necrosis Factor-alpha; Malnutrition
PubMed: 36372284
DOI: 10.1016/j.exger.2022.112025 -
Molecules (Basel, Switzerland) Mar 2018Acute inflammation is a protective response of the host to physical injury and invading infection. Timely treatment of acute inflammatory reactions is essential to...
Acute inflammation is a protective response of the host to physical injury and invading infection. Timely treatment of acute inflammatory reactions is essential to prevent damage to organisms that can eventually lead to chronic inflammation. Forsythoside A (FTA), an active constituent of , has been reported to have anti-inflammatory, antioxidant, and antibacterial properties. Despite increasing knowledge of its anti-inflammatory effects, the mechanism and the effects on acute inflammation are poorly understood. This study is aimed at exploring the pro-resolving effects of FTA on zymosan-induced acute peritonitis. FTA significantly alleviated peritonitis as evidenced by the decreased number of neutrophils and levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in the peritoneal cavity, without interfering with interleukin-10 (IL-10). FTA showed marked regulation of inflammatory cytokines and chemokine levels in zymosan-stimulated RAW 264.7 macrophages. Moreover, FTA could suppress the activation of NF-κB. In conclusion, FTA alleviated zymosan-induced acute peritonitis through inhibition of NF-κB activation.
Topics: Animals; Anti-Inflammatory Agents; Cytokines; Glycosides; Inflammation Mediators; Mice; NF-kappa B; Neutrophils; Peritoneal Cavity; Peritonitis; RAW 264.7 Cells; Zymosan
PubMed: 29509714
DOI: 10.3390/molecules23030593 -
Mediators of Inflammation 2017(.) is the most common causative pathogen in peritonitis, the second most common cause of sepsis. Granzymes (gzms) are serine proteases traditionally implicated in...
(.) is the most common causative pathogen in peritonitis, the second most common cause of sepsis. Granzymes (gzms) are serine proteases traditionally implicated in cytotoxicity and, more recently, in the inflammatory response. We here sought to investigate the role of gzms in the host response to -induced peritonitis and sepsis in vivo. For this purpose, we used a murine model of intraperitoneal infection, resembling the clinical condition commonly associated with septic peritonitis by this bacterium, in wild-type and gzmA-deficient ( ), , and mice. GzmA and gzmB were predominantly expressed by natural killer cells, and during abdominal sepsis, the percentage of these cells expressing gzms in peritoneal lavage fluid decreased, while the amount of expression in the gzm cells increased. Deficiency of gzmA and/or gzmB was associated with increased bacterial loads, especially in the case of gzmB at the primary site of infection at late stage sepsis. While gzm deficiency did not impact neutrophil recruitment into the abdominal cavity, it was accompanied by enhanced nucleosome release at the primary site of infection, earlier hepatic necrosis, and more renal dysfunction. These results suggest that gzms influence bacterial growth and the host inflammatory response during abdominal sepsis caused by .
Topics: Animals; Escherichia coli; Female; Granzymes; Male; Mice; Mice, Inbred C57BL; Neutrophil Infiltration; Nucleosomes; Peritonitis; Sepsis
PubMed: 28694562
DOI: 10.1155/2017/4137563 -
Reproductive Sciences (Thousand Oaks,... May 2015Endometriosis is a multifactorial disease mostly affecting women of reproductive age. An additive effect between inflammation and stress reaction on the growth of...
Endometriosis is a multifactorial disease mostly affecting women of reproductive age. An additive effect between inflammation and stress reaction on the growth of endometriosis has been demonstrated. Here we investigated the combined effect between 17β-estradiol (E2) and lipopolysaccharide (LPS) on pelvic inflammation and growth of endometriotic cells. Peritoneal fluid was collected from 46 women with endometriosis and 30 control women during laparoscopy. Peritoneal macrophages (Mφ) and stromal cells from eutopic/ectopic endometrial stromal cells (ESCs) were isolated from 10 women each with and without endometriosis in primary culture. Changes in cytokine secretion (interleukin 6 [IL-6] and tumor necrosis factor α [TNF-α]) by Mφ and proliferation of ESCs in response to single and combined treatment with E2 and LPS were measured by enzyme-linked immunosorbent assay and by bromodeoxyuridine incorporation assay, respectively. A significantly increased secretion of IL-6 and TNF-α in Mφ culture media was found in response to E2 (10(-8) mol/L) compared to nontreated Mφ. This effect of E2 was abrogated after pretreatment of cells with ICI 182720 (10(-6) mol/L; an estrogen receptor [ER] antagonist). Combined treatment with E2 and LPS (10 ng/mL) additively promoted IL-6 and TNF-α secretion by peritoneal Mφ and growth of eutopic/ectopic ESCs. The additive effects of E2 + LPS on cytokine secretion and growth of ESCs were effectively suppressed after combined blocking of ER and Toll-like receptor 4. An additive effect was observed between E2 and LPS on promoting proinflammatory response in pelvis and growth of endometriosis.
Topics: Adolescent; Adult; Anti-Inflammatory Agents; Case-Control Studies; Cell Proliferation; Cells, Cultured; Endometriosis; Endometrium; Estradiol; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Humans; Inflammation Mediators; Interleukin-6; Lipopolysaccharides; Macrophages, Peritoneal; Receptors, Estrogen; Stromal Cells; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 25355803
DOI: 10.1177/1933719114556487 -
PloS One 2022Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy but the underlying mechanism remains obscure. The aims of this study are to...
Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy but the underlying mechanism remains obscure. The aims of this study are to examine if omental adipose tissue (OMAT) and subcutaneous AT (SCAT) differentially express proinflammatory and lipid metabolic adipokines, and if so, whether their regional differences have implications on lipid metabolism in GDM. Paired samples of OMAT and SCAT were excised from pregnant women in scheduled Cesarean sections with non-obese (NOBS), obese (OBS) and GDM. The results showed that the mRNA of monocyte chemoattractant protein (MCP)-1, macrophage marker CD68, and cytokines IL-6, IL-8, and TNF-α are increased in OMAT from GDM women compared to that in NOBS and OBS women (P<0.05). Glucose and TNF-α dose-dependently enhanced ADM and its receptor components CRLR and RAMPs in human adipocytes. Immunofluorescence showed that ADM and its receptor components are higher in OMAT from GDM women compared to non-GDM women. Further, basal lipolysis was greater in OMAT than in SCAT and ADM stimulates further glycerol release in OMAT, but not in SCAT, and these increases are reduced by ADM antagonist, ADM22-52. We therefore conclude that elevated ADM and its receptor expressions by OMAT, but not by SCAT appear to contribute to the lipid dysregulation in GDM women, and manipulation of ADM may represent one of the novel approaches in minimizing the risk of GDM-related fetal overgrowth.
Topics: Adipose Tissue; Adrenomedullin; Diabetes, Gestational; Female; Fetal Macrosomia; Humans; Lipids; Obesity; Omentum; Pregnancy; Subcutaneous Fat; Tumor Necrosis Factor-alpha
PubMed: 35390031
DOI: 10.1371/journal.pone.0265419 -
World Journal of Gastroenterology Apr 2020Hepatic portal venous gas (HPVG) generally indicates poor prognoses in patients with serious intestinal damage. Although surgical removal of the damaged portion is...
BACKGROUND
Hepatic portal venous gas (HPVG) generally indicates poor prognoses in patients with serious intestinal damage. Although surgical removal of the damaged portion is effective, some patients can recover with conservative treatments.
AIM
To establish an optimal treatment strategy for HPVG, we attempted to generate computed tomography (CT)-based criteria for determining surgical indication, and explored reliable prognostic factors in non-surgical cases.
METHODS
Thirty-four cases of HPVG (patients aged 34-99 years) were included. Necessity for surgery had been determined mainly by CT findings (. free-air, embolism, lack of contrast enhancement of the intestinal wall, and intestinal pneumatosis). The clinical data, including treatment outcomes, were analyzed separately for the surgical cases and non-surgical cases.
RESULTS
Laparotomy was performed in eight cases (surgical cases). Seven patients (87.5%) survived but one (12.5%) died. In each case, severe intestinal damage was confirmed during surgery, and the necrotic portion, if present, was removed. Non-occlusive mesenteric ischemia was the most common cause ( = 4). Twenty-six cases were treated conservatively (non-surgical cases). Surgical treatments had been required for twelve but were abandoned because of the patients' poor general conditions. Surprisingly, however, three (25%) of the twelve inoperable patients survived. The remaining 14 of the 26 cases were diagnosed originally as being sufficiently cured by conservative treatments, and only one patient (7%) died. Comparative analyses of the fatal ( = 10) and recovery ( = 16) cases revealed that ascites, peritoneal irritation signs, and shock were significantly more frequent in the fatal cases. The mortality was 90% if two or all of these three clinical findings were detected.
CONCLUSION
HPVG related to intestinal necrosis requires surgery, and our CT-based criteria are probably useful to determine the surgical indication. In non-surgical cases, ascites, peritoneal irritation signs and shock were closely associated with poor prognoses, and are applicable as predictors of patients' prognoses.
Topics: Adult; Aged; Aged, 80 and over; Ascites; Conservative Treatment; Embolism, Air; Female; Gases; Humans; Intestinal Mucosa; Male; Mesenteric Ischemia; Necrosis; Pneumatosis Cystoides Intestinalis; Portal Vein; Prognosis; Retrospective Studies; Risk Factors; Shock; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 32327911
DOI: 10.3748/wjg.v26.i14.1628