scholarly journals Lure-and-kill macrophage nanoparticles alleviate the severity of experimental acute pancreatitis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiangzhe Zhang ◽  
Julia Zhou ◽  
Jiarong Zhou ◽  
Ronnie H. Fang ◽  
Weiwei Gao ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Membrane Lipids ◽  
Pancreatic Acinar Cells ◽  
Dependent Manner ◽  
Disease Mechanism ◽  
Effective Protection ◽  
Coated Nanoparticles ◽  
Wide Range ◽  
Dose Dependent ◽  
Macrophage Membrane

AbstractAcute pancreatitis is a disease associated with suffering and high lethality. Although the disease mechanism is unclear, phospholipase A2 (PLA2) produced by pancreatic acinar cells is a known pathogenic trigger. Here, we show macrophage membrane-coated nanoparticles with a built-in ‘lure and kill’ mechanism (denoted ‘MΦ-NP(L&K)’) for the treatment of acute pancreatitis. MΦ-NP(L&K) are made with polymeric cores wrapped with natural macrophage membrane doped with melittin and MJ-33. The membrane incorporated melittin and MJ-33 function as a PLA2 attractant and a PLA2 inhibitor, respectively. These molecules, together with membrane lipids, work synergistically to lure and kill PLA2 enzymes. These nanoparticles can neutralize PLA2 activity in the sera of mice and human patients with acute pancreatitis in a dose-dependent manner and suppress PLA2-induced inflammatory response accordingly. In mouse models of both mild and severe acute pancreatitis, MΦ-NP(L&K) confer effective protection against disease-associated inflammation, tissue damage and lethality. Overall, this biomimetic nanotherapeutic strategy offers an anti-PLA2 treatment option that might be applicable to a wide range of PLA2-mediated inflammatory disorders.

scholarly journals Necroptosis protects against exacerbation of acute pancreatitis

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Michittra Boonchan ◽  
Hideki Arimochi ◽  
Kunihiro Otsuka ◽  
Tomoko Kobayashi ◽  
Hisanori Uehara ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Necrotizing Pancreatitis ◽  
Neutrophil Infiltration ◽  
Dependent Manner ◽  
Protective Effects ◽  
Interacting Protein ◽  
Inflammatory Conditions ◽  
Edematous Pancreatitis ◽  
Genetic Deletion ◽  
Dose Dependent

AbstractThe sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3−/− or Mlkl−/− mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3−/− mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl−/− mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl−/− mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue damage. Genetic deletion of Mlkl resulted in downregulation of the antiapoptotic genes Bclxl and Cflar in association with increases in the numbers of apoptotic cells, as detected by TUNEL assay. These findings suggest that RIPK3 and MLKL-mediated necroptosis exerts protective effects in AP and caution against the use of necroptosis inhibitors for AP treatment.

scholarly journals NLRP3 Deficiency Alleviates Severe Acute Pancreatitis and Pancreatitis-Associated Lung Injury in a Mouse Model

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Qiang Fu ◽  
Zhensheng Zhai ◽  
Yuzhu Wang ◽  
Lixia Xu ◽  
Pengchong Jia ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Nlrp3 Inflammasome ◽  
Early Death ◽  
Neutrophil Infiltration ◽  
Multiple Organ ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Nlrp3 Expression

The rapid production and release of a large number of inflammatory cytokines can cause excessive local and systemic inflammation in severe acute pancreatitis (SAP) and multiple organ dysfunction syndrome (MODS), especially pancreatitis-associated acute lung injury (P-ALI), which is the main cause of early death in patients with SAP. The NLRP3 inflammasome plays an important role in the maturation of IL-1β and the inflammatory cascade. Here, we established a model of SAP using wild-type (NLRP3+/+) and NLRP3 knockout (NLRP3-/-) mice by intraperitoneal injections of caerulein (Cae) and lipopolysaccharide (LPS). Pathological injury to the pancreas and lungs, the inflammatory response, and neutrophil infiltration were significantly mitigated in NLRP3-/- mice. Furthermore, INF-39, an NLRP3 inflammasome inhibitor, could reduce the severity of SAP and P-ALI in a dose-dependent manner. Our results suggested that SAP and P-ALI were alleviated by NLRP3 deficiency in mice, and thus, reducing NLRP3 expression may mitigate SAP-associated inflammation and P-ALI.

scholarly journals Rhein Induces a Necrosis-Apoptosis Switch in Pancreatic Acinar Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Xianlin Zhao ◽  
Juan Li ◽  
Shifeng Zhu ◽  
Yiling Liu ◽  
Jianlei Zhao ◽  
...  
Keyword(s):  
Annexin V ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Necrotic Cell ◽  
Ar42j Cells ◽  
Associated Proteins ◽  
Apoptosis And Necrosis ◽  
Dose Dependent

Objectives. The Chinese herbal medicine Da-Cheng-Qi decoction can regulate a necrosis-apoptosis switch in injured pancreatic acinar cells. This study investigated the effects of rhein, a component of this medicine, on a necrosis-apoptosis switch in pancreatic rat AR42J cells.Methods. Cerulein-treated AR42J cells were used. After pretreatment with 479, 119.8, or 29.9 μg/L rhein, cells were cocultured with rhein and cerulein (10−8 M) for 4, 8, or 16 h. Apoptosis and necrosis were examined using annexin V and propidium iodide costaining. Mitochondria-dependent apoptosis-associated proteins were examined using enzyme-linked immunosorbent assays and western blotting.Results. Few cells died in untreated samples. The number was significantly higher in 16-h-cerulein-treated samples and treatment with 479 μg/L rhein most effectively increased the apoptotic-to-necrotic cell ratio (P<0.05). In cerulein-treated cells, rhein increased the concentrations of p53, cytochrome C, and caspase-3, and increased the Bax/Bcl-2 ratio in a time- and dose-dependent manner, with the maximum effect in cells treated with 479 μg/L rhein for 16 h (P<0.05).Conclusions. Rhein induces the necrosis-apoptosis switch in injured pancreatic acinar cells in a time- and dose-dependent manner. Mitochondria-dependent apoptosis signaling pathways might play an important role in this effect.

scholarly journals Calcium and calmodulin in the regulation of human thyroid adenylate cyclase activity

1985 ◽  
Vol 225 (3) ◽  
pp. 581-589 ◽  
Author(s):  
T Lakey ◽  
S Mac Neil ◽  
H Humphries ◽  
S W Walker ◽  
D S Munro ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Metal Ion ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Human Thyroid ◽  
Dependent Manner ◽  
Biphasic Response ◽  
Thyroid Stimulating Immunoglobulins ◽  
Wide Range ◽  
Dose Dependent

TSH (thyrotropin)-stimulated human thyroid adenylate cyclase has a biphasic response to Ca2+, being activated by submicromolar Ca2+ (optimum 22nM), with inhibition at higher concentrations. Calmodulin antagonists caused an inhibition of TSH-stimulated adenylate cyclase in a dose-dependent manner. Inhibition of TSH-and TSIg-(thyroid-stimulating immunoglobulins)-stimulated activity was more marked than that of basal, NaF- or forskolin-stimulated activity. This inhibition was not due to a decreased binding of TSH to its receptor. Addition of pure calmodulin to particulate preparations of human non-toxic goitre which had not been calmodulin-depleted had no effect on adenylate cyclase activity. EGTA was ineffective in removing calmodulin from particulate preparations, but treatment with the tervalent metal ion La3+ resulted in a loss of up to 98% of calmodulin activity from these preparations. Addition of La3+ directly to the adenylate cyclase assay resulted in a partial inhibition of TSH- and NaF-stimulated activity, with 50% inhibition produced by 5.1 microM and 4.0 microM-La3+ respectively. Particulate preparations with La3+ showed a decrease of TSH- and NaF-stimulated adenylate cyclase activity (approx. 40-60%). In La3+-treated preparations there was a decrease in sensitivity of TSH-stimulated adenylate cyclase to Ca2+ over a wide range of Ca2+ concentrations, but most markedly in the region of the optimal stimulatory Ca2+ concentration. In particulate preparations from which endogenous calmodulin had been removed by La3+ treatment, the addition of pure calmodulin caused an increase (73 +/- 22%; mean +/- S.E.M., n = 8) in TSH-stimulated thyroid adenylate cyclase activity. This was seen in 8 out of 13 experiments.

OxLDL Inhibits Brain Angiogenesis in Dose Dependent Manner via Reducing Level of VEGF and Angiopoietin-2: A Comprehensive Study

2017 ◽  
Author(s):  
Tasneem Alniqrish ◽  
Saed Khawaldeh
Keyword(s):  
Endothelial Cells ◽  
Human Brain ◽  
Angiogenic Factor ◽  
Microvascular Endothelial Cells ◽  
Dependent Manner ◽  
Brain Microvascular Endothelial Cells ◽  
Wide Range ◽  
Microvascular Endothelial ◽  
Dose Dependent ◽  
Brain Angiogenesis

Hyperlipidemia is recognized as a major health problem worldwide, moreover, it is considered as a major risk factor for cardiovascular and cerebrovascular diseases development. Since the majority of studies were performed to investigate the effect of hyperlipidemia on the angiogenesis of peripheral derived endothelial cell, this study aims to assess the effect of hyperlipidemia on the angiogenic response of human brain cells in a fast, easy and inexpensive method. Furthermore, it aims also to assess the involvement of Vascular Endothelial Growth Factor (VEGF) and angiopoietin. To achieve this aim, human Brain Microvascular Endothelial Cells (hBMECs) were treated with different concentration of Oxidized Low Density Lipoprotein (OxLDL) (1-100 μg/ml) for 24 hours. Migration rate and tube formation as markers of angiogenesis were performed, also Coomassie blue was used to detect protein level. OxLDL was found to inhibit brain angiogenesis in dose dependent manner over a wide range of concentrations (1-100 μg/ml). Using 1 μg/ml of OxLDL made minimum reduction of 10% whereas using 100 μg/ml of OxLDL resulted 70-80% reduction in the angiogenic potential of hBMECs within 24 hours. Moreover, OxLDL mediated its effect through reduced VEGF level and this effect was partially reversed by administered 5 ng/ml of VEGF. Additionally, OxLDL reduced the level of angiopoitin-2. This further supports the assumption that OxLDL has an anti-angiogenic effect in hBMECs and surely in the brain also. As a conclusion, OxLDL inhibits brain angiogenesis in dose dependent manner through reducing the level of angiogenic factor in human brain microvascular endothelial cells. We achieved our goal of having a preliminary indicator of brain angiogenesis under hyperlipidemia by using a simple but well-developed technique that incorporated the minimal number of tests and the cheapest.

scholarly journals Antioxidant, anti-inflammatory and anticoagulant activities of three Thymus species grown in southeastern Morocco

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Abdelbassat Hmidani ◽  
Eimad Dine Tariq Bouhlali ◽  
Tarik Khouya ◽  
Mhamed Ramchoun ◽  
Younes Filali-Zegzouti ◽  
...  
Keyword(s):  
Anticoagulant Activity ◽  
Activated Partial Thromboplastin Time ◽  
Dependent Manner ◽  
Thrombin Time ◽  
Thymus Zygis ◽  
Wide Range ◽  
Thymus Satureioides ◽  
Anti Inflammatory ◽  
Dose Dependent

Abstract Background Thyme has been used for centuries in southeastern Morocco to treat a wide range of diseases such as inflammation disorders. The aim of the current study is to examine and to compare in vitro the anti-inflammatory, antioxidant, and anticoagulant activities of three thyme species grown in southeastern Morocco. Results Data showed that all studied species possess an important antioxidant activity: Thymus atlanticus (IC50 = 16.59 μg/mL), Thymus zygis (IC50 = 15.43 μg/mL), and Thymus satureioides (IC50 = 14.65 μg/mL). Concerning the anti-inflammatory activity, the highest effect was depicted in Thymus atlanticus followed by Thymus zygis and Thymus satureioides. With regard to the anticoagulant activity, the aqueous extract of these species prolongs activated partial thromboplastin time, prothrombin time, and thrombin time significantly (p < 0.05) in a dose-dependent manner. Conclusion Our results provide evidence that thymus extract exhibits marked antioxidant, anticoagulant, and anti-inflammatory effects, thus justifying the popular uses of these plants to treat some inflammatory and cardiovascular illnesses.

Studies on the Antimicrobial Activity of Juglans regia

1997 ◽  
Vol 25 (02) ◽  
pp. 175-180 ◽  
Author(s):  
Abdulaziz M. Alkhawajah
Keyword(s):  
Antimicrobial Activity ◽  
Juglans Regia ◽  
Dependent Manner ◽  
Pathogenic Yeast ◽  
Gram Positive Bacteria ◽  
Additive Action ◽  
Esherichia Coli ◽  
Wide Range ◽  
Micro Organisms ◽  
Dose Dependent

Juglans regia L. bark is used in some countries as a toothbrush and as a dye for coloring the lips for cosmetic purposes. Its extract showed a broad spectrum antimicrobial activity in a dose dependent manner. It inhibited the growth of several species of pathogenic micro-organisms representing Gram-positive bacteria (Staphylococcus aureus and Streptococcus mutans), Gram-negative bacteria (Esherichia coli and Pseudomonas aeruginosa) and a pathogenic yeast (Candida albicans). The extract has either synergistic or additive action when tested with a wide range of antibacterial drugs. It also increased the pH of saliva. Thus, brushing the teeth with this bark may improve oral hygiene, prevent plaque and caries formation, and reduce the incidence of gingival and periodontal infections.

scholarly journals Isolation, Identification and Molecular Characterization of Pathogenic Fungus causing bud Rot Disease to Coconut: Its Inhibition using Silkworm Fecal Matter Mediated Synthesized Silver and Copper Nanoparticles

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Avinash B
Keyword(s):  
Copper Nanoparticles ◽  
Pathogenic Fungus ◽  
Nano Particles ◽  
Phytophthora Palmivora ◽  
Dependent Manner ◽  
Fecal Matter ◽  
Wide Range ◽  
Rot Disease ◽  
Dose Dependent

Coconut is one the major economic crop in India; a considerable amount of crop will be lost every year due to bud rot disease. Phytophthora palmivora is an omnipresent pathogen which causes many different diseases on a wide range of plants including bud rot of coconut. In the present investigation, we have successfully isolated bud rot disease causing fungus from the infected coconut plant samples. The isolated fungus was primarily identified by observing in microscopy further the same sample was sent for molecular identification. The presence of Phytophthora palmivora was confirmed in 18s rRNA sequencing. The growth of isolated fungus was effectively inhibited using biosynthesized Silver and Copper nanoparticles. The inhibition effects of nanoparticles against Phytophthora palmivora were observed excellent in dose-dependent manner. The silver nanoparticles synthesized using Silkworm fecal matter was shown superior inhibition activity towards Phytophthora palmivora compare to standard fungicide Fluconazole. Hence, these silver Nano particles could be successfully used in inhibiting the pathogenic fungus causing bud rot disease to coconut.

Diarylheptanoids: Potent Anticancer Agents

2021 ◽  
Vol 08 ◽  
Author(s):  
Rabia Hameed
Keyword(s):  
T Cell Activation ◽  
Anticancer Agents ◽  
Cell Activation ◽  
Dependent Manner ◽  
Current Review ◽  
Tnf Α ◽  
Wide Range ◽  
The Family ◽  
Dose Dependent

Abstract: Diarylheptanoids are widely distributed among species belonging to the family Betulaceae. Being highly polar in nature, they can either be isolated from plants by using sophisticated chromatographic techniques or can be synthesized in the laboratory. They are found to exhibit a wide range of activities, from very simple analgesics to anticancer agents. Recently, they have gained considerable attention due to inhibitory activity against NF-κB activation, NO and TNF-α production, reduction in NO and COX-2 levels in a dose-dependent manner, and suppression of T-cell activation. The current review article highlights the role of diarylheptanoids as potent anticancer agents in a variety of cancers.

Evaluation of antigenotoxic effects of diosgenin in mice exposed to cyclophosphamide

2018 ◽  
Vol 9 (1) ◽  
pp. 96
Author(s):  
Hema G ◽  
Subbarao D ◽  
Thippeswamy BS
Keyword(s):  
Lipid Peroxidation ◽  
Reduced Glutathione ◽  
Steroidal Saponin ◽  
Dependent Manner ◽  
Chemotherapeutic Drugs ◽  
Immune Parameters ◽  
Wide Range ◽  
Dose Dependent ◽  
Antigenotoxic Effects ◽  
Wild Yam

Diosgenin is a steroidal saponin found in a variety of plants including fenugreek and roots of wild yam and is widely used in traditional medicine systems. Diosgenin is shown to have anti-invasive, anti-proliferative and proapoptotic activities on wide range of cancer cells and a well known precursor of various synthetic steroidal drugs that are extensively used in the pharmaceutical industry. The present investigation explores the genotoxic and antigenotoxic properties of diosgenin in experimental mice exposed to cyclophosphamide. CP increases the formation of micronucleated PCEs in the bone marrow of mice significantly and lowers the total WBC. In mice pre-treated with diosgenin, the formation of mnPCEs is lowered in a dose dependent manner and the immune parameters are restored. Diosgenin also reduces the lipid per oxidation levels indicated by MDA assessment and restores the antioxidant GSH in the liver tissues of the mice, counteracting the effects of CP. In our study, Diosgenin did not exhibit inherent genotoxic properties nor had a synergistic effect with CP. These results indicate the potential of diosgenin as an antigenotoxic agent with a possibility to be used as an adjuvant, to counteract the side-effects of chemotherapeutic drugs.  Keywords: Antigenotoxicity; Cyclophosphamide; Diosgenin; Micronucleated PCEs; WBC; Lipid peroxidation; Reduced glutathione

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