Mcgarryskafte5973
Alterations of plasma membrane fluidity are characteristic of many diseases but the intentional modulation of membrane fluidity with drugs has been less studied. We examined the therapeutic potential of the membrane fluidizer diethyl azelate (DEA) and related azelates.
The effects of azelates on plasma membrane fluidity and cell signaling were examined in primary human and murine cells and in vivo. Endpoints were queried using single target and multiplexed immunoassays.
Unique membrane-fluidizing properties and biomarker signatures suggest that azelates are not prodrugs. DEA decreased cytokine signaling from pattern recognition receptors in human dendritic cells, disabled membrane attack of cholera toxin in vitro, and prevented immunosuppression by anthrax lethal toxin in vitro and in vivo. In the murine sepsis model, DEA increased survival and reduced organ damage.
Azelates represent a new class of drugs, membrane active immunomodulators, which target an innate homeostatic mechanism, adaptive membrane fluidity modulation.
Azelates represent a new class of drugs, membrane active immunomodulators, which target an innate homeostatic mechanism, adaptive membrane fluidity modulation.
Triple-negative matrix-producing breast carcinoma (MPBC) is rare, recalcitrant, and highly aggressive. The present study aimed to determine the efficacy of tumor-targeting leucine-arginine auxotroph Salmonella typhimurium (S. typhimurium) A1-R on a triple-negative MPBC in a patient-derived orthotopic xenograft (PDOX) model.
The PDOX MPBC model was established in the left second mammary gland of nude mice by surgical orthotopic implantation (SOI). PDOX models were randomized into two groups when the tumor volume reached over 70 mm
a control group (n=6); and a tumor-targeting S. typhimurium A1-R group (n=7), [intravenous (i.v.) injection of S. typhimurium A1-R via the tail vein, weekly, for two weeks]. All mice were sacrificed on day 14. Tumor volume and body weight were measured once per week.
S. typhimurium A1-R exquisitely targeted and arrested the growth of the MPBC PDOX compared to the control group (p=0.017).
S. typhimurium A1-R has future clinical potential for triple-negative MPBC patients.
S. typhimurium A1-R has future clinical potential for triple-negative MPBC patients.
The role of senescence and bone marrow-derived cells in silica-induced pulmonary fibrosis is unknown.
C57BL/6HNsd, p16
, and tdTOMp16+ mice were intratracheally injected with 200 mg/kg crystalline silica or irradiated (20 Gy) to the thoracic cavity and followed for the development of lung fibrosis.
The p16
mice demonstrated senescence by day 7 after silica exposure. C57BL/6 mice exposed to silica demonstrated upregulation of p16, p21, and tyrosine kinase Fgr by day 7, whereas thoracic irradiation induced p21 and Fgr by day 50 and p16 by day 110. Silica exposed GFP+ bone marrow chimeric C57BL/6 mice demonstrated senescent cells and gfp+/Fgr+ monocyte/macrophages in the lungs on day 21. The Fgr inhibitor TL02-59 abrogated monocyte/macrophages recruitment in in vitro transwell experiments.
Both silica and radiation exposure induce senescence and upregulate tyrosine kinase Fgr for the recruitment of bone marrow-derived monocyte/macrophages and the development of pulmonary fibrosis.
Both silica and radiation exposure induce senescence and upregulate tyrosine kinase Fgr for the recruitment of bone marrow-derived monocyte/macrophages and the development of pulmonary fibrosis.Adamantinoma is a biphasic tumor, with a low potential for malignancy, characterized by clusters of epithelial cells surrounded by a relatively bland spindle-cell osteofibrous component. The aim of the present study was to review the updated data regarding epidemiology; pathogenesis; clinical presentation; radiological, histopathological and ultrastructural findings; and treatment options of adamantinoma. In X-ray, it is usually seen as an eccentric and sometimes central, lobular, lytic lesion with sclerotic margins of overlapping radiolucency, and a characteristic 'soap-bubble' appearance. Magnetic resonance imaging seems to be the most appropriate examination for differential diagnosis between adamantinoma and other skeletal tumors. Histologically, adamantinoma is identified as classic adamantinoma or osteofibrous-like adamantinoma. Classic adamantinoma is classified into four patterns of growth Basaloid, tubular, spindle cell, and squamous. The preferable treatment of this tumor type is en bloc resection within wide operative margins, which may include suspicious regional lymph nodes, with limb reconstruction and limb salvage.Certain diseases and age groups are associated with a higher incidence of cancer. learn more Cancer prevention can be achieved using repositioned drugs that have anticancer ability, thereby reducing the incidence of cancer in susceptible individuals. This implies that the selection of repositioned drugs can have dual benefits controlling pre-existing diseases and facilitating cancer prevention. This report outlines the rationale underlying drug repositioning for medications with an anticancer effect and discusses its advantages. We discuss repositioned drugs with anticancer effects that may contribute to cancer prevention in susceptible individuals and the general population with temporary, treatable conditions. The discussion of drug repositioning in this review should facilitate the initiation of clinical trials and lead to therapeutic application of such drugs to reduce the incidence of cancer in susceptible individuals.Lipomatous meningioma (LM) is a form of metaplasia, originating from intracellular lipid bodies accumulation due to metabolic alterations. A comprehensive literature review was performed introducing further elements of evaluation. The parameters utilized were age, sex, location, clinical presentation, imaging features, treatment, and recurrences. Seizure and headache are the primary onsets of symptoms. Further LM clinical features, such as visual disturbances and visual epileptic seizures were examined. Symptoms may occur ten years prior to LM finding and it can resolve completely with the indicated surgery. LM computed tomography imaging analysis reveals hypodense regions due to the presence of fat content. On magnetic resonance imaging, the lesion displays hyperintense signal in T1-T2 with signal loss in the fat-suppression sequences. Immunohistochemically, lipidized meningioma cells are positive for Epithelial-Membrane Antigen, Vimentin, CD99, S-100 protein, and progesterone receptor. The recurrence risk rate of LM is estimated to be around 17%. Precise immune-histological findings have been correlated with imaging features to help with early diagnosis. A defined diagnosis of LM is a crucial factor in the choice of treatment.
Postdural puncture headache (PDPH) is one of the earliest recognized complications of regional anesthesia after inadvertent dural puncture. Epidural blood patch (EBP) is the "gold standard" for the treatment of PDPH. Several alternatives have been suggested as peripheral nerve blocks. The aim of this systematic review was to find out the potential efficacy and safety of peripheral nerve blocks for the treatment of PDPH.
The main databases were systematically searched in September 2020 for studies examining regional anesthesia and PDPH.
Nineteen studies were identified, including a total of 221 patients. Sphenopalatine ganglion block, greater occipital nerve block, and lesser occipital nerve block were performed. All participants reported a numeric rating scale (NRS) <4 after peripheral nerve blocks at 1, 24 and 48 h. Only patients with PDPH after diagnostic lumbar puncture reported NRS ≥4 after 48 h. No major adverse events were reported. Approximately, 17% of patients underwent a second or more peripheral nerve blocks. In 30 participants, EBP was required.
To our knowledge, this is the first systematic review on the use of peripheral nerve blocks to treat PDPH. Peripheral nerve blocks can be considered as analgesic options in the management of PDPH.
To our knowledge, this is the first systematic review on the use of peripheral nerve blocks to treat PDPH. Peripheral nerve blocks can be considered as analgesic options in the management of PDPH.In many medical disciplines, the process of drilling into the bone plays a crucial role for the implantation or fixation of implants or reconstruction plates. During the bone drilling process, heat is generated on the drill head and within the surrounding tissue. As a result, the increased temperature can lead to thermal damage and related necrosis of the (bone) tissue. This tissue damage is dependent on different drilling parameters and can have important influence on the following tissue healing cascade and finally on implant surveillance. In this context, the present short review elucidates the current state of scientific knowledge with regard to the heat-triggering factors during the bony drilling process and how these factors can be better understood and prevented, now and in the future, through new research approaches. External and internal influencing factors during the drilling process are distinguished and methods to examine the temperature changes are compared. This mini-review further demonstrates first preliminary results of the inflammatory tissue reactions to inadequate drilling processes. Furthermore, possible solutions of new standardized ex vivo-measurement methods to better understand the factors influencing the development of heat and to reduce animal experiments are herein discussed.The elderly people are characterized by multiple comorbidities, dementia, and are at risk of developing sarcopenia and frailty. Sarcopenia is defined by loss of muscle mass and muscle strength or physical decline. Sarcopenia is a main component of physical frailty. Screening tools for sarcopenia that can be easily determined in daily practice are useful and include the SARC-F screening tool. SARC-F is a questionnaire consisting of five questions Strength (S), Assistance walking (A), Rising from a chair (R), Climbing stairs (C), and Falls (F) on a scale of 0 to 2. The recommended cutoff value is ≥4 points. The SARC-F has been shown to correlate well with clinical outcomes in the elderly and various underlying diseases, while it is also true that the SARC-F has its shortcomings such as low sensitivity for sarcopenia. In this review, we mainly outline the SARC-F and mention other screening tools for sarcopenia.The structure of the plasma membrane affects its function. Changes in membrane fluidity with concomitant effects on membrane protein activities and cellular communication often accompany the transition from a healthy to a diseased state. Although deliberate modulation of membrane fluidity with drugs has not been exploited to date, the latest data suggest the "druggability" of the membrane. Azelaic acid esters (azelates) modulate plasma membrane fluidity and exhibit a broad range of immunomodulatory effects in vitro and in vivo. Azelates represent a new class of drugs, membrane active immunomodulators (MAIMs), which use the entire plasma membrane as the target, altering the dynamics of an innate feedback regulated homeostatic system, adaptive membrane fluidity modulation (AMFM). A review of the literature data spanning >200 years supports the notion that molecules in the MAIMs category including known drugs do exert immunomodulatory effects that have been either neglected or dismissed as off-target effects.
