Transplanted Fibroblasts Proliferate in Host Bronchial Tissue and Enhance Bronchial Anastomotic Healing in a Rodent Model

2017 ◽  
Vol 40 (9) ◽  
pp. 515-521
Author(s):  
Mario Vitacolonna ◽  
Fabian Doyon ◽  
Djeda Belharazem ◽  
Charalambos Tsagogiorgas ◽  
Peter Hohenberger ◽  
...  
Keyword(s):  
Cell Tracking ◽  
Cell Concentration ◽  
Main Bronchus ◽  
Subcutaneous Fat ◽  
Clinical Problem ◽  
Underlying Mechanism ◽  
Preoperative Irradiation ◽  
Fischer 344 ◽  
A Cell ◽  
Bronchial Tissue

Introduction Healing of airway anastomoses after preoperative irradiation can be a significant clinical problem. The augmentation of bronchial anastomoses with a fibroblast-seeded human acellular dermis (hAD) was shown to be beneficial, although the underlying mechanism remained unclear. Therefore, in this study we investigated the fate of the fibroblasts transplanted to the scaffold covering the anastomosis. Material and methods 32 Fisher rats underwent surgical anastomosis of the left main bronchus. In a 2 × 2 factorial design, they were randomized to receive preoperative irradiation of 20 Gy and augmentation of the anastomosis with a fibroblast-seeded transplant. Fibroblasts from subcutaneous fat of Fischer-344 rat were transduced retrovirally with tdTomato for cell tracking. After 7 and 14 days, animals were sacrificed and cell concentration of transplanted and nontransplanted fibroblasts in the hAD as well as in the bronchial tissue was measured using RT-PCR. Results Migration of transplanted fibroblasts from dermis to bronchus were demonstrated in both groups, irradiated and nonirradiated. In the irradiated groups, there was a cell count of 7 × 104 ± 1 × 104 tomato+-fibroblasts in the bronchial tissue at day 7, rising to 1 × 105 ± 1 × 104 on day 14 (p<0.0001). Tomato+-cell concentration in hAD increased from 6 × 103 ± 1 × 103 at day 7 to 6 × 104 ± 1 × 104 at day 14 (p<0.0001). In the nonirradiated groups, tomato+-cell concentration in bronchus was 4 × 103 ± 1 × 103 on day 7 and 4 × 103 ± 1 × 103 at day 14. In the hAD tomato+ cell concentration rising from 1 × 104 ± 1 × 103 at day 7 to 2 × 104 ± 3 × 103 cells at day 14 (p = 0.0028). Conclusions Transplanted fibroblasts in the irradiated groups proliferate and migrate into the irradiated host bronchial tissue, but not in the nonirradiated groups.

scholarly journals Repression of Acetaminophen-Induced Hepatotoxicity in HepG2 Cells by Polyphenolic Compounds from Lauridia tetragona (L.f.) R.H. Archer

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2118 ◽  
Author(s):  
Samuel Odeyemi ◽  
John Dewar
Keyword(s):  
Hepg2 Cells ◽  
Antioxidant Properties ◽  
Reducing Power ◽  
Underlying Mechanism ◽  
Hepatoprotective Activity ◽  
Polyphenolic Compounds ◽  
Hepatocellular Injury ◽  
Liver Glutathione ◽  
Total Antioxidant ◽  
A Cell

Lauridia tetragona (L.f) R.H. Archer is routinely used in traditional medicine; however, its hepatoprotective property is yet to be scientifically proven. To this effect, the hepatoprotective activity of the polyphenolic-rich fractions (PPRFs) was investigated against acetaminophen (APAP) injured HepG2 cells. The ability of the PPRF to scavenge free radicals was tested against 2,2-diphenyl-1-picrylhydrazyl (DPPH), and [2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonicacid)] (ABTS). The ferric ion reducing power (FRAP) was also evaluated as a cell-free antioxidant assay. The hepatoprotective activity was then investigated by observing the effect of PPRFs against APAP-induced reduction in cell viability of HepG2 cells. The concentrations of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and lactate dehydrogenase (LDH) released into the medium were evaluated while the underlying mechanism was further explored through western blot analysis. Thereafter, the isolated PPRFs were identified using UHPLC-QToF-MS. All six fractions of the PPRFs isolated showed significant antioxidant properties that were evident by the effective scavenging of DPPH, ABTS, and higher FRAP. The results indicated that PPRF pretreatments ameliorated APAP-induced hepatocellular injury by significantly inhibiting the leakage of AST, ALT, and LDH into the medium. The most active fractions for hepatoprotection were PPRF4 and PPRF6 with IC50 of 50.243 ± 8.03 and 154.59 ± 1.9 μg/mL, respectively. PPRFs markedly increased activities of liver superoxide dismutase, total antioxidant capacity, and liver glutathione concentration. Both PPRF4 and PPRF6 significantly increased the expression of Nrf2 and translocation. The LC-MS analysis revealed the presence of a wide variety of polyphenolics such as coumarin, ferulic acid, and caffeine among the dominant constituents. In conclusion, this study demonstrates that the isolated PPRFs have potential hepatoprotective activity that may be due to the increased expression of antioxidative genes dependent on Nrf2.

scholarly journals A 10-Year Study on the Characteristics of Thunderstorms in Belgium Based on Cloud-to-Ground Lightning Data

2014 ◽  
Vol 142 (12) ◽  
pp. 4839-4849 ◽  
Author(s):  
Dieter R. Poelman
Keyword(s):  
Cell Tracking ◽  
Total Activity ◽  
The West ◽  
European Cooperation ◽  
Lightning Detection ◽  
Cloud To Ground Lightning ◽  
A Cell ◽  
Direction Of Movement ◽  
Temporal And Spatial ◽  
The Individual

Abstract Temporal and spatial distributions of cloud-to-ground (CG) lightning in Belgium are analyzed. Based on data from the European Cooperation for Lightning Detection (EUCLID) network, spanning a period of 10 years between 2004 and 2013, mean CG flash densities vary between 0.3 km−2 yr−1 in the west up to 2.4 km−2 yr−1 toward the east of Belgium, with an average flash density of 0.7 km−2 yr−1. The same behavior is found in terms of thunderstorm days and hours, where in the east most of the activity is observed, with a drop-off toward the coast. The majority of lightning activity takes place in the summer months between May and August, accounting for nearly 90% of the total activity. Furthermore, the thunderstorm season reaches its highest activity in July in terms of CG detections, while the diurnal cycle peaks between 1500 and 1600 UTC. A correlation is found between the estimated peak currents and altitude, with on average higher absolute peak currents at lower elevations and vice versa. In addition, a cell tracking algorithm is applied to the data to monitor the behavior of the individual cells. It is found that the lightning cells travel at an average speed of about 25 km h−1, with a preferred northeasterly direction of movement. At last, CG flash rates are strongly related to the cell area.

scholarly journals In B cells, phosphatidylinositol 5-phosphate 4-kinase–α synthesizes PI(4,5)P2 to impact mTORC2 and Akt signaling

2016 ◽  
Vol 113 (38) ◽  
pp. 10571-10576 ◽  
Author(s):  
Simon J. Bulley ◽  
Alaa Droubi ◽  
Jonathan H. Clarke ◽  
Karen E. Anderson ◽  
Len R. Stephens ◽  
...  
Keyword(s):  
Time Course ◽  
Mammalian Target Of Rapamycin ◽  
Underlying Mechanism ◽  
Phosphatidylinositol 3 Kinase ◽  
Akt Phosphorylation ◽  
Endogenous Protein ◽  
Lipid Kinases ◽  
A Cell ◽  
Genetic Deletion ◽  
Dt40 Cells

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are enigmatic lipid kinases with physiological functions that are incompletely understood, not the least because genetic deletion and cell transfection have led to contradictory data. Here, we used the genetic tractability of DT40 cells to create cell lines in which endogenous PI5P4Kα was removed, either stably by genetic deletion or transiently (within 1 h) by tagging the endogenous protein genomically with the auxin degron. In both cases, removal impacted Akt phosphorylation, and by leaving one PI5P4Kα allele present but mutating it to be kinase-dead or have PI4P 5-kinase activity, we show that all of the effects on Akt phosphorylation were dependent on the ability of PI5P4Kα to synthesize phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] rather than to remove PI5P. Although stable removal of PI5P4Kα resulted in a pronounced decrease in Akt phosphorylation at Thr308 and Ser473, in part because of reduced plasma membrane PIP3, its acute removal led to an increase in Akt phosphorylation only at Ser473. This process invokes activation primarily of mammalian target of rapamycin complex 2 (mTORC2), which was confirmed by increased phosphorylation of other mTORC2 substrates. These findings establish PI5P4Kα as a kinase that synthesizes a physiologically relevant pool of PI(4,5)P2 and as a regulator of mTORC2, and show a phenomenon similar to the “butterfly effect” described for phosphatidylinositol 3-kinase Iα [Hart JR, et al. (2015) Proc Natl Acad Sci USA 112(4):1131–1136], whereby through apparently the same underlying mechanism, the removal of a protein’s activity from a cell can have widely divergent effects depending on the time course of that removal.

scholarly journals A Curious Case of PTH Independent Hypercalcemia Secondary to Silicone Injections

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A176-A176
Author(s):  
Moises Matos ◽  
Ahsan Farooq ◽  
Heidi Jackeline Peynado De Pena ◽  
Hanford Yau ◽  
Asif Uddin
Keyword(s):  
African American Woman ◽  
Subcutaneous Fat ◽  
American Woman ◽  
Clinical Problem ◽  
Surgical Debridement ◽  
Severe Hypercalcemia ◽  
Granulomatous Tissue ◽  
Granulomatous Diseases ◽  
Silicone Injections

Abstract Background: Hypercalcemia is a commonly encountered clinical problem with numerous etiologies. Granulomas formed secondary to foreign bodies are a rare but increasingly recognized cause of hypercalcemia. Clinical Case: A 49-year old African American woman, who had received silicone injections for buttock augmentation 15 years ago, was found to have severe hypercalcemia after she presented with complaints of chronic constipation, muscle cramping, polyuria, and mental fog. Her labs on admission showed severe hypercalcemia Ca 17.9mg/dL (normal: 8.4–10.6 mg/dL), with a suppressed PTH 4 pg/mL (normal 14–54 pg/mL). Prior labs from 5 years earlier, had shown an elevated 1,25(OH)2D, therefore differentials including lymphoma and chronic granulomatous diseases, particularly sarcoidosis, were high on the list of possible diagnosis. Additional labs showed a normal PTH-RP 19 pg/mL (normal 14–27 pg/mL), normal ACE levels 64 U/L (normal 9–67 U/L), low 25(OH)D2 1 ng/mL and normal 1,25(OH)2D 62 pg/mL. Her exam was notable for multiple indurated and firm masses palpable over the bilateral gluteal region and lateral thighs. CT abdomen/pelvis showed extensive and markedly confluent infiltration with intervening globules of macroscopic fat throughout the subcutaneous fat layers of the buttocks and lateral hips and speckled linear calcifications consistent with granulomatous reaction. With aggressive fluid hydration and calcitonin, her calcium levels decreased over the following 48 hours, but remained at 12–13 mg/dL. She was started on 30 mg of prednisone daily and her calcium levels dropped to 10.9 mg/dL the following day. She was discharged home on prednisone, her calcium levels remained suppressed, and her prednisone dose was slowly tapered during the following months. She was referred for plastic surgery evaluation and is being evaluated for possible surgical debridement. Conclusion: Hypercalcemia secondary to foreign body granulomas is a rare clinical entity. The diagnosis is usually established through a thorough history and examination. Lab findings may be variable. Treatment of these patients can be challenging, and corticosteroids are the mainstay of treatment in most cases1. Surgical debridement of granulomas has been reported with good results; however, further investigation and longer follow-up is needed2. References: 1.Tachamo, N., Donato, A., Timilsina, B., Nazir, S., Lohani, S., Dhital, R., & Basnet, S. Hypercalcemia associated with cosmetic injections: A systematic review. European Journal of Endocrinology, 2018; 178(4): 425–4302.Edwards, B.J., Saraykar, S., Suna, M., Murphy, W. A., Lin, P., Gagel, R. Resection of granulomatous tissue resolves silicone induced hypercalcemia, Bone Reports, 2016; 5:163–7

scholarly journals Calcium Ion Chelation Preserves Platelet Function During Cold Storage

2020 ◽  
Author(s):  
Binggang Xiang ◽  
Guoying Zhang ◽  
Yan Zhang ◽  
Congqing Wu ◽  
Smita Joshi ◽  
...  
Keyword(s):  
Platelet Function ◽  
Cold Storage ◽  
Calcium Ion ◽  
Platelet Transfusion ◽  
Room Temperature ◽  
Underlying Mechanism ◽  
Integrin Activation ◽  
Life Saving ◽  
A Cell ◽  
Rapid Clearance

Objective: Platelet transfusion is a life-saving therapy to prevent or treat bleeding in patients with thrombocytopenia or platelet dysfunction. However, for >6 decades, safe and effective strategies for platelet storage have been an impediment to widespread use of platelet transfusion. Refrigerated platelets are cleared rapidly from circulation, precluding cold storage of platelets for transfusion. Consequently, platelets are stored at room temperature with an upper limit of 5 days due to risks of bacterial contamination and loss of platelet function. This practice severely limits platelet availability for transfusion. This study is to identify the mechanism of platelet clearance after cold storage and develop a method for platelet cold storage. Approach and Results: We found that rapid clearance of cold-stored platelets was largely due to integrin activation and apoptosis. Deficiency of integrin β3 or caspase-3 prolonged cold-stored platelets in circulation. Pretreatment of platelets with EGTA, a cell impermeable calcium ion chelator, reversely inhibited cold storage-induced platelet activation and consequently prolonged circulation of cold-stored platelets. Moreover, transfusion of EGTA-treated, cold-stored platelets, but not room temperature-stored platelets, into the mice deficient in glycoprotein Ibα significantly shortened tail-bleeding times and diminished blood loss. Conclusions: Integrin activation and apoptosis is the underlying mechanism of rapid clearance of platelets after cold storage. Addition of a cell impermeable calcium ion chelator to platelet products is potentially a simple and effective method to enable cold storage of platelets for transfusion.

scholarly journals Validation of Short-Term Forecasting of Meso-^|^gamma;-Scale Convective Systems Based on a Cell-Tracking System

SOLA ◽  
2012 ◽  
Vol 8 (0) ◽  
pp. 141-144 ◽  
Author(s):  
Syo Yoshida ◽  
Ryohei Misumi ◽  
Shingo Shimizu ◽  
Takeshi Maesaka ◽  
Koyuru Iwanami ◽  
...  
Keyword(s):  
Cell Tracking ◽  
Tracking System ◽  
Short Term ◽  
Convective Systems ◽  
A Cell ◽  
Short Term Forecasting

scholarly journals Mechanisms of Human intelligence — From RNA and Synapse to Broadband

2019 ◽  
Author(s):  
Robert Traill
Keyword(s):  
Underlying Mechanism ◽  
Long Term Memory ◽  
Optical Signals ◽  
A Cell ◽  
Impossible Task ◽  
The Many ◽  
The Right ◽  
Label Sequence

Simple thought has been explained by the action-potential (AP) system with its synapses. In contrast, in-depth details for “Declarative” intellectual thought have been a complete mystery because (it is argued here) its main underlying mechanism is fundamentally different. Declarative thinking depends heavily on linear coding based on digit-like elements — something which an unaided AP system could never offer......Looking instead to psychology, Piaget (1920s) proposed basic units of action-sequences (“schèmes” whereby one could mentally construct object-concepts). There is now evidence that some ncRNA serves this verb-like action-coding role. — (Other ncRNA demonstrably serves as adjectival/adverbial “regulators” — while the remaining ≈3% of RNA encodes physical structures, the traditional noun-like role). If valid, then:–•NEW FOCUS ONTO ULTRAMICRO: — The whole Piagetian structure-coding for a concept could fit into one of the many 125nm capsids (“granules”). Moreover, many more concepts (and duplicates) could fit into a cell-body. — The vast abundance of coding-sites would allow comprehensive “wasteful” rapid use of Jerneian/Darwinian selection instead of problematic “writing down” of new learnings. — Estimates of memory-capacity increase vastly. — And hereditary-schèmes obviously explain inherited behaviour-traits. — Piaget’s other theory about develop¬mental stages also seems compatible.•Quantum-constraints ensure that such micro-sites would USE OPTICAL FREQUENCY signalling. That opens the way to greatly enhanced “Gigabit” rates, and optical-interference tricks.•MYELIN gets the EXTRA ROLE OF OPTIC-CABLE.So nerve-fibres become seen as simultan¬eous paths for two different types of signal (also demonstrated by Sun-et-al, 2010), with AP still dominant in some roles, but subservient to “UPE” optical signals elsewhere.•LOCATING MEMORIES? Choosing the right address means selecting some sort of “phone-number or numbered plug-socket.” That is best provided as an “address-label” sequence on the transmitted version of the schème-coding — in which case, actual destination-location may be less important.•“Moving-house” TO CORTICAL LONG-TERM MEMORY. The memory-move must preserve existing (i) memory-structure, and (ii) links to distant static archives. This “impossible” task would seem feasible if memories are actually held within individual cells (as above). There is indeed lifelong flow of such neurons in some mammals; but these flows seem to cease in adulthood for humans and dolphins! So the search continues.

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