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Nutrients Sep 2023A high-fat diet (HFD) is a major risk factor for cardiovascular diseases. Many pure compounds have been demonstrated to be effective in treating cardiovascular diseases....
A high-fat diet (HFD) is a major risk factor for cardiovascular diseases. Many pure compounds have been demonstrated to be effective in treating cardiovascular diseases. In this study, we investigated the alleviating effects of oral ovatodiolide and antcin K (OAK) supplements on HFD-induced cardiovascular dysfunction in apolipoprotein E (ApoE)-knockout mice. Cardiovascular dysfunction was induced in ApoE-knockout mice by feeding them an HFD for 12 weeks. The degree of cardiovascular dysfunction was assessed through echocardiography, hematological and biochemical analyses, and immunofluorescence and immunohistochemical staining. The HFD-fed mice exhibited cardiovascular dysfunction-abnormal blood biochemical index. The arterial wall tissue exhibited the marked deposition of lipids, upregulated expression of vascular cell adhesion molecule-1 and CD36 receptors, and downregulated expression of the ABCA1 receptor. Macrophages isolated from the peritoneal cavity of the mice exhibited increased levels of lipid accumulation, reactive oxygen species, and CD11b expression but reduced mitochondrial membrane potential. The expression of superoxide dismutase 2 was downregulated and that of tumor necrosis factor-α was upregulated in the myocardial tissue. Oral OAK supplements twice a day for 12 weeks significantly mitigated HFD-induced cardiovascular dysfunction in the experimental mice. Oral OAK supplements appear to be a promising strategy for treating HFD-induced cardiovascular dysfunction. The underlying mechanisms may involve the reduction of lipid accumulation in the artery and oxidative stress and inflammation in the cardiovascular tissue.
Topics: Animals; Mice; Diet, High-Fat; Cardiovascular Diseases; Oxidative Stress; Apolipoproteins E
PubMed: 37764856
DOI: 10.3390/nu15184074 -
Antioxidants (Basel, Switzerland) Sep 2023Acute kidney injury and chronic kidney disease are among the most common non-communicable diseases in the developed world, with increasing prevalence. Patients with... (Review)
Review
Acute kidney injury and chronic kidney disease are among the most common non-communicable diseases in the developed world, with increasing prevalence. Patients with acute kidney injury are at an increased risk of developing chronic kidney disease. One of kidney injury's most common clinical sequelae is increased cardiovascular morbidity and mortality. In recent years, new insights into the pathophysiology of renal damage have been made. Oxidative stress is the imbalance favoring the increased generation of ROS and/or reduced body's innate antioxidant defense mechanisms and is of pivotal importance, not only in the development and progression of kidney disease but also in understanding the enhanced cardiovascular risk in these patients. This article summarizes and emphasizes the role of oxidative stress in acute kidney injury, various forms of chronic kidney disease, and also in patients on renal replacement therapy (hemodialysis, peritoneal dialysis, and after kidney transplant). Additionally, the role of oxidative stress in the development of drug-related nephrotoxicity and also in the development after exposure to various environmental and occupational pollutants is presented.
PubMed: 37760075
DOI: 10.3390/antiox12091772 -
Frontiers in Immunology 2023C-reactive protein (CRP) levels are elevated in patients with abdominal aortic aneurysms (AAA). However, it has not been investigated whether CRP contributes to AAA...
BACKGROUND
C-reactive protein (CRP) levels are elevated in patients with abdominal aortic aneurysms (AAA). However, it has not been investigated whether CRP contributes to AAA pathogenesis.
METHODS
CRP deficient and wild type (WT) male mice were subjected to AAA induction via transient intra-aortic infusion of porcine pancreatic elastase. AAAs were monitored by measurements of maximal infrarenal aortic external diameters immediately prior to and 14 days following elastase infusion. Key AAA pathologies were assessed by histochemical and immunohistochemical staining procedures. The influence of CRP deficiency on macrophage activation was evaluated in peritoneal macrophages .
RESULTS
CRP protein levels were higher in aneurysmal than that in non-aneurysmal aortas. Aneurysmal aortic dilation was markedly suppressed in CRP deficient (aortic diameter: 1.08 ± 0.11 mm) as compared to WT (1.21 ± 0.08 mm) mice on day 14 after elastase infusion. More medial elastin was retained in CRP deficient than in WT elastase-infused mice. Macrophage accumulation was significantly less in aneurysmal aorta from CRP deficient than that from WT mice. Matrix metalloproteinase 2 expression was also attenuated in CRP deficient as compared to WT aneurysmal aortas. CRP deficiency had no recognizable influence on medial smooth muscle loss, lymphocyte accumulation, aneurysmal angiogenesis, and matrix metalloproteinase 9 expression. In assays, mRNA levels for tumor necrosis factor α and cyclooxygenase 2 were reduced in lipopolysaccharide activated peritoneal macrophages from CRP deficient as compared to wild type mice.
CONCLUSION
CRP deficiency suppressed experimental AAAs by attenuating aneurysmal elastin destruction, macrophage accumulation and matrix metalloproteinase 2 expression.
Topics: Humans; Male; Animals; Mice; Swine; Matrix Metalloproteinase 2; C-Reactive Protein; Elastin; Aortic Aneurysm, Abdominal; Aorta, Abdominal
PubMed: 37753091
DOI: 10.3389/fimmu.2023.1233807 -
PNAS Nexus Sep 2023Malignant ascites in hepatocellular carcinoma is usually a sign of advanced disease and poor prognosis and is also thought to be associated with chronic inflammation...
Malignant ascites in hepatocellular carcinoma is usually a sign of advanced disease and poor prognosis and is also thought to be associated with chronic inflammation mediated by neutrophil extracellular trap (NET) networks. Although ozone, a strong oxidant, has significant antibacterial and anti-inflammatory effects, its effectiveness in treating malignant liver ascites is unclear. We first measured the levels of NETs in the peripheral blood of patients with liver cancer and healthy individuals. Next, we constructed the H22 tumor-bearing mouse model and observed the abdominal girth, body weight, survival rate, and survival time in each group; we marked the proteins associated with NETs in mouse intestinal tissues by immunofluorescence; cf-DNA and cytokines in ascites such as: tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), matrix metalloprotein 9 (MMP-9), and interferon gamma (IFN-γ) levels in ascites were measured by enzyme-linked immunosorbent assay. The expression levels of phosphorylated adenylate-activated protein kinase (P-AMPK) and scavenger receptor-A (SR-A) were detected by immunocytochemistry in the intestinal tissues of each group of mice. We further examined the expression of P-AMPK and SR-A proteins in ascites deposits by Western blotting. The results show, the plasma levels of NETs were higher in patients with hepatocellular carcinoma than in normal subjects ( < 0.01). Abdominal girth and body weight were significantly reduced in the ozone-treated group compared with the model group, while survival and survival time were dose dependently increased (both < 0.05). NET-associated guanine histone H3 and myeloperoxidase were abundantly expressed at neutrophil aggregates in the intestinal tissues of the model mice, whereas their expression was significantly reduced in the ozone-treated group. The levels of cf-DNA, IL-6, IFN-γ, MMP-9, VEGF, and TNF-α were dose dependently increased in the ascites of H22 tumor-bearing mice in the ozone-treated group compared with the model group (all < 0.01), while the expression of P-AMPK and SR-A proteins was increased in the ozone-treated group compared with the model group. Ozone showed significant antiperitoneal fluid production properties in H22 tumor-bearing mice, and ozone reduced peritoneal fluid production by activating AMPK and up-regulating SR-A phagocytosis damage-associated molecular patterns to reduce the production of NETs. This suggests that ozone could be used as a new drug for the treatment of malignant ascites in hepatocellular carcinoma.
PubMed: 37693209
DOI: 10.1093/pnasnexus/pgad280 -
Mediators of Inflammation 2023Sepsis is a life-threatening clinical condition caused by infection and transposition of pathogens and pathogen-associated molecular patterns (PAMPs) into the host...
Sepsis is a life-threatening clinical condition caused by infection and transposition of pathogens and pathogen-associated molecular patterns (PAMPs) into the host bloodstream. During sepsis, activation of toll-like receptors (TLRs) on immune cells triggers the release of pro-inflammatory cytokines and overstimulates the production of vasodilatory mediators such as nitric oxide (NO). These vascular changes lead to widespread inflammation, tissue damage, multiple organ failure, and often death. New therapeutic options are urgently needed. To this end, thiostrepton (TST) has emerged as a candidate for sepsis treatment due to its action as an antibiotic and anti-inflammatory molecule (TLR7-9 inhibitor). Reports in the literature suggest that TLR9 inhibition substantially suppresses the excessive host inflammatory response and attenuates sepsis-induced mortality in the cecal ligation and puncture (CLP) murine model of sepsis. However, to the best of our knowledge, TST has never been directly tested as a therapeutic option for the management of sepsis, possibly due to its low water solubility and drug delivery issues. These facts prompted us to test the central hypothesis that TST encapsulated in phospholipid sterically stabilized micelles (TST-SSM) could be developed into a novel treatment for sepsis. Thus, using our published method of encapsulating the hydrophobic antibiotic TST-SSM, we evaluated the efficacy of TST-SSM nanomedicine in the murine model of polymicrobial sepsis. We found that TST-SSM increased the median survival of CLP-induced septic mice from 31 to 44 hr by reducing the bacterial burden in the blood and peritoneal lavage. Moreover, plasma levels of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor-alpha) and NO derivatives were also reduced, whereas renal and hepatic function biomarkers creatinine and aspartate transferase were significantly improved. In conclusion, we identified that TST-SSM nanomedicine has significant potential as a therapeutic agent for sepsis management, primarily due to its anti-inflammatory and antibiotic properties.
Topics: Animals; Mice; Thiostrepton; Toll-Like Receptor 9; Disease Models, Animal; Nanomedicine; Sepsis; Inflammation; Anti-Bacterial Agents; Cytokines
PubMed: 37662481
DOI: 10.1155/2023/4035516 -
Cureus Jul 2023The present study focuses on ileosigmoid knotting (ISK), an infrequent but potentially lethal surgical emergency. ISK is more frequently observed in males and is...
The present study focuses on ileosigmoid knotting (ISK), an infrequent but potentially lethal surgical emergency. ISK is more frequently observed in males and is prevalent in regions with high rates of sigmoid volvulus. The current medical scenario revolves around the intricate intertwining of the ileum and sigmoid colon, leading to a complicated volvulus. This condition often results in acute intestinal obstruction, which can subsequently cause bowel necrosis. The clinical presentation of the condition is characterized by symptoms such as abdominal distention, pain, vomiting, and obstipation, which can be misleading as they are similar to other common abdominal conditions. A delay in definitive diagnosis and intervention is likely, which can lead to severe consequences such as peritonitis, bowel necrosis, sepsis, and even septic shock. Our case report discusses an instance of ISK presenting as an acute abdomen requiring an emergency laparotomy and detorsion of the volvulus-knotted segment, followed by an elective sigmoidectomy. The significance of a heightened level of suspicion, prompt decision-making, and timely surgical intervention in achieving better patient outcomes cannot be overstated. The objective is to enhance the medical community's understanding of ISK, focusing on early diagnosis and effective treatment of this rare but life-threatening disease.
PubMed: 37654963
DOI: 10.7759/cureus.42749 -
The Pan African Medical Journal 2023Mesenteric panniculitis is a primary inflammation of the mesentery with variable necrosis, inflammation and fibrosis of the fatty tissue. It can be idiopathic (primary)...
[A rare triple combination of mesenteric panniculitis, acute appendicitis and König´s syndrome in a patient operated for acute febrile intestinal obstruction: a case report].
Mesenteric panniculitis is a primary inflammation of the mesentery with variable necrosis, inflammation and fibrosis of the fatty tissue. It can be idiopathic (primary) or secondary (associated) to other diseases, asymptomatic and accidentally discovered or revealed by abdominal pain or complications (intestinal obstruction or peritonitis). We here report the case of a 53-year-old patient, admitted with acute abdominal pain, cessation of the transit of materials and gases, in a febrile context. Patient's history included chronic abdominal pain suggesting König´s syndrome and epigastralgia lasting several years. Physical examination showed sore face and abdominal examination revealed mild bloating, marked tenderness in the right iliac fossa (RIF) and in the periumbilical region, without guarding or rigidity and borygms heard on auscultation and with normal rectal examination. A diagnosis of bowel obstruction and fever was made, with suspicion of meso-celiac appendicitis. Abdominal X-ray without preparation and ultrasound confirmed the diagnosis of bowel occlusion. Exploratory laparotomy revealed functional stenosis of the ileum (König´s syndrome) at 1.20m from the ileocecal junction, with multiple adhesions. Adhesiolysis revealed hyperemic appendix measuring 15cm long, whose anatomo pathological examination showed a mucous membrane with inflammatory infiltrate and a wall rich in polynuclear cells. Infiltration of the ileal mesentery causing color change (reddish and greyish in some areas) and small nodosities with friability and tearing on simple handling led to suspicion of mesenteric panniculitis, then confirmed by anatomopathological examination, showing inflammatory reaction in the fatty tissue specimen with infiltration by macrophages, associated with necrotic patches and degeneration. Treatment was based on bowel emptying, anterograde appendectomy, and a combination of corticosteroid (Dexamethasone 24 mg/day) and chymotrypsin (10000 IU/day). The patient´s outcome was good and he was discharged in the 10 postoperative day. The patient underwent clinical and paraclinical follow-up (3 months) for another unknown associated pathology or a pathology that may have occurred early.
Topics: Male; Humans; Middle Aged; Appendicitis; Panniculitis, Peritoneal; Digestive System Diseases; Intestinal Obstruction; Inflammation; Acute Disease; Abdominal Pain
PubMed: 37637396
DOI: 10.11604/pamj.2023.45.57.19448 -
Indian Journal of Critical Care... Aug 2023A serious problem in cirrhosis is acute renal injury. The study aimed to examine the urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a diagnostic and...
Urinary Neutrophil Gelatinase-associated Lipocalin as a Diagnostic and Prognostic Marker for Acute Kidney Injury in Hospitalized Cirrhotic Patients: A Study from North Indian Population.
BACKGROUND
A serious problem in cirrhosis is acute renal injury. The study aimed to examine the urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a diagnostic and prognostic marker of acute kidney injury (AKI) in cirrhotic patients.
METHODS
A prospective study was carried out over a period of 1 year. A total of 490 patients suffering from cirrhosis who visited an indoor hospital were screened, and after the exclusion, a total of 90 subjects admitted to the medicine intensive care unit (MICU) fulfilling inclusion criteria were enrolled. Those having a history of renal diseases, on nephrotoxic drugs, in septic shock, peritonitis, UTI, and no urine output were excluded. On admission, for the estimation of uNGAL, urinary levels of sodium, creatinine, fresh urine samples were obtained, and blood samples were taken for serum creatinine estimation.
RESULTS
Out of 90 patients, 33.3% did not develop AKI, and 66.7% developed AKI. Urinary neutrophil gelatinase-associated lipocalin levels were six times higher in patients with acute tubular necrosis (259.08 ± 118.41 ng/mL) and three times higher in Hepatorenal syndrome (HRS)-AKI (124.97 ± 16.38) as compared with patients with normal kidney function (39.76 + 5.7). Those who died had a higher uNGAL (171.6 ng/mL) in comparison to those who survived (133.7 ng/mL). At a cutoff value of ≥114.9 (ng/mL), urinary NGAL represents a sensitivity of 86.92% and specificity of 100% to diagnose AKI and AUC 0.966 (95% CI: 0.919-0.990) in cirrhotic patients.
CONCLUSION
Urinary NGAL is good for diagnosing AKI and is a marker to distinguish the types of AKI in liver cirrhosis.
HOW TO CITE THIS ARTICLE
Patel ML, Shyam R, Chaudhary A, Sachan R, Ali W. Urinary Neutrophil Gelatinase-associated Lipocalin as a Diagnostic and Prognostic Marker for Acute Kidney Injury in Hospitalized Cirrhotic Patients: A Study from North Indian Population. Indian J Crit Care Med 2023;27(8):545-551.
PubMed: 37636847
DOI: 10.5005/jp-journals-10071-24497 -
International Journal of Molecular... Aug 2023Turbot aquaculture production is an important economic activity in several countries around the world; nonetheless, the incidence of diseases, such furunculosis, caused...
Turbot aquaculture production is an important economic activity in several countries around the world; nonetheless, the incidence of diseases, such furunculosis, caused by the etiological agent subsp. , is responsible for important losses to this industry worldwide. Given this perspective, this study aimed to evaluate early immune responses in turbot ( L.) following infection with subsp. . For this, 72 fish were individually weighed and randomly distributed into 6 tanks in a circulating seawater system. For the bacterial challenge, half of the individuals (3 tanks with 36 individuals) were infected using a peritoneal injection with the bacterial suspension, while the other half of individuals were injected with PBS and kept as a control group. Several factors linked to the innate immune response were studied, including not only haematological (white blood cells, red blood cells, haematocrit, haemoglobin, mean corpuscular volume, mean cell haemoglobin, mean corpuscular haemoglobin concentration, neutrophils, monocytes, lymphocytes, thrombocytes) and oxidative stress parameters, but also the analyses of the expression of 13 key immune-related genes (, , , , , , , , , , , , ). No significant differences were recorded in blood or innate humoral parameters (lysozyme, anti-protease, peroxidase) at the selected sampling points. There was neither any evidence of significant changes in the activity levels of the oxidative stress indicators (catalase, glutathione S-transferase, lipid peroxidation, superoxide dismutase). In contrast, pro-inflammatory (, ), anti-inflammatory (), and innate immune-related genes () were up-regulated, while another gene linked with the lipid metabolism () was down-regulated. The results showed new insights about early responses of turbot following infection with subsp. .
Topics: Animals; Flatfishes; Immunity, Innate; Interleukin-10; Tumor Necrosis Factor-alpha
PubMed: 37629124
DOI: 10.3390/ijms241612944 -
World Journal of Clinical Cases Aug 2023Chest wall tuberculosis (TB) and triple-negative essential thrombocythemia (TN-ET) are rare medical conditions, and their combination is extremely rare globally. Only...
BACKGROUND
Chest wall tuberculosis (TB) and triple-negative essential thrombocythemia (TN-ET) are rare medical conditions, and their combination is extremely rare globally. Only one case of TB peritonitis with thrombocytosis has been reported, which was identified in 1974.
CASE SUMMARY
Herein, we report the case of a 23-year-old man with concurrent chest wall mass and TN-ET. The patient presented to a local hospital due to having a headache and low-grade fever for 2 d, with their bodily temperature fluctuating at around 36.8 °C. Hematological analysis showed a high platelet count of 1503 × 10/L. Subsequently, the patient visited our hospital for further investigation. Computed tomography of the chest suggested a submural soft tissue density shadow in the left lower chest wall. After surgical resection, the pathological findings of the swelling were reported as TB with massive caseous necrosis. According to the World Health Organization diagnostic criteria, the patient was diagnosed with TN-ET, as they met the requirement of four main criteria or the first three main criteria and one secondary criterion. The patient was eventually diagnosed with chest wall TB with TN-ET, which is extremely rare.
CONCLUSION
Chest wall TB is rare. TN-ET diagnosis requires secondary factor exclusion and satisfaction of primary diagnostic criteria. miRNA, combined with the methylation process, could explain suppressor of cytokine signaling (SOCS) 1 and SOCS3 downregulation in ET-JAK2V617F-negative patients. The miRNA could participate in JAK2 pathway activation. SOCS3 may be a novel MPN biomarker.
PubMed: 37621591
DOI: 10.12998/wjcc.v11.i22.5365