Tannic acid prevents macrophage-induced pro-fibrotic response in lung epithelial cells via suppressing TLR4-mediated macrophage polarization

Background

Polarized macrophages induce fibrosis through multiple mechanisms, including a process termed epithelial-to-mesenchymal transition (EMT). Mesenchymal cells contribute to the excessive accumulation of fibrous connective tissues, leading to organ failure. This study was aimed to investigate the effect of tannic acid (TA), a natural dietary polyphenol on M1 macrophage-induced EMT and its underlying mechanisms.

Materials

First, we induced M1 polarization in macrophage cell lines (RAW 264.7 and THP-1). Then, the conditioned-medium (CM) from these polarized macrophages was used to induce EMT in the human adenocarcinomic alveolar epithelial (A549) cells. We also analysed the role of TA on macrophage polarization.

Results

We found that TA pre-treated CM did not induce EMT in epithelial cells. Further, TA pre-treated CM showed diminished activation of MAPK in epithelial cells. Subsequently, TA was shown to inhibit LPS-induced M1 polarization in macrophages by directly targeting toll-like receptor 4 (TLR4), thereby repressing LPS binding to TLR4/MD2 complex and subsequent signal transduction.

Conclusion

It was concluded that TA prevented M1 macrophage-induced EMT by suppressing the macrophage polarization possibly through inhibiting the formation of LPS-TLR4/MD2 complex and blockage of subsequent downstream signal activation. Further, our findings may provide beneficial information to develop new therapeutic strategies against chronic inflammatory diseases.

     

Heart-rate tuned comb filters for processing photoplethysmogram (PPG) signals in pulse oximetry

Journal of Clinical Monitoring and Computing - Calculation of peripheral capillary oxygen saturation $${\text{(SpO}}_{{\text{2}}} {\text{)}}$$ levels in humans is often made with a pulse oximeter,...     

Chylous ascites: a rare complication of radical gastrectomy

Chylous ascites is the accumulation of lymphatic fluid within the peritoneal cavity, due to trauma or obstruction to the lymphatic system. Postoperative chylous ascites is a rare complication of abdominal surgery. This is frequently reported after retroperitoneal dissections, and results in high morbidity and mortality. The treatment options are varied and include total parenteral nutrition (TPN), elemental diet with medium chain triglycerides (MCT), repeated paracentesis and surgical ligation. We report a case of post-operative chylous ascites after D2 distal gastrectomy. Treatment by fasting, TPN followed by fat-free diet resulted in complete resolution of ascites within 3 weeks. To our knowledge this is the first report of such a complication following radical gastrectomy. We review the literature and briefly discuss the management options.     

Prolonged growth of activated B lymphocytes requires interaction with helper T cells

Resting B lymphocytes acquire upon activation responsiveness to soluble factors that support their growth and differentiation. We have studied the growth requirements of anti-mu pre-activated B lymphocytes in vitro. We found that activated B lymphocytes did respond to soluble factors from helper T cells by entering the cell cycle but cell-cell contact with specific helper T cells was required for prolonged growth of activated B lymphocytes. Thus, activated B lymphocytes must receive activation signals from helper T cells in order to stay in the proliferative phase of the cell cycle.     

T-cell anergy: a consequence of interaction between T cells and allogeneic rat renal epithelial cells

Abstract In order to study the immunogenicity of parenchymal cells within an allograft, renal tubular cells were propagated from both PVG and DA strain rats. These cells were induced to express class II major histocompatibility (MHC) antigens by stimulation for 4 days with interferon-gamma (IFN- y ). It was found that resting lymphoid cells derived from Lewis rats responded vigorously after stimulation with irradiated splenic cells from PVG rats. However, stimulation with renal cells from PVG rats did not result in interleukin (IL-2) production or lymphoprolife-ration. Furthermore, lymphocytes from this mixture failed to respond to secondary stimulation by PVG splenic cells; lymphocytes primed by mixture with DA renal cells responded normally to secondary stimulation by PVG splenic cells. These results indicate that renal epithelial cells can specifically anergise allogeneic lymphocytes.     

Renoprotective action of L-carnitine in fructose-induced metabolic syndrome

Aim:  Rats fed high dosage of fructose that form a well-known experimental model of the metabolic syndrome also display progressive renal disturbances. The present study evaluates the influence of l -carnitine (CA) administration on oxidant–antioxidant balance, protein damage and lipid levels in kidney of rats administered high dose of fructose.
Methods:  Adult male Wistar rats were divided into four groups of 10 rats each. Groups I and IV animals received starch-based control diet, while groups II and III rats were fed a high-fructose diet (60 g/100 g). Groups III and IV animals additionally received CA (300 mg/kg/day) for 60 days. The extent of lipid peroxidation, enzymatic and non-enzymatic antioxidants and lipid levels were measured after 60 days. The accumulation of nitrated and oxidatively modified proteins in kidney was also measured by immunohistochemical study with specific antibodies.
Results:  Fructose-fed rats exhibited increased levels of peroxidation end products, diminished antioxidant status, increased staining for the presence of 4-hydroxy-2-nonenal, 2,4-dinitrophenol and 3-nitrotyrosine protein adducts and lipid accumulation in kidney. CA administration attenuated these pathological renal alterations.
Conclusions:  The benefits of CA in this model suggest the therapeutic use of CA to counter the kidney changes associated with metabolic syndrome.     

Implications of contrast-enhanced CT-based and MRI-based target volume delineations in radiotherapy treatment planning for brain tumors

Delineation of various target volumes using contrast-enhanced magnetic resonance imaging (MRI) and/or computed tomography (CT) constitutes the primary step for radiation therapy planning (RTP) in brain tumors. This study presents a quantification and comparative evaluation of the various clinical target volumes (CTV) and gross target volumes (GTV) as outlined by contrast-enhanced CT and MRI, along with its implications for postoperative radiotherapy of brain tumors. Twenty-one patients of gliomas were considered for this prospective study. Peritumoral edema as CTV and residual tumor as GTV were delineated separately in postoperative contrast-enhanced CT and MRI. These volumes were estimated separately and their congruence studied for contrast-enhanced CT and MRI. Compared to MRI, CT underestimated the volumes, with significant differences seen in the mean CTV (mean +/- SD: -62.92 +/- 93.99 cc; P = 0.006) and GTV (mean +/- SD: -21.08 +/- 36.04 cc; P = 0.014). These differences were found to be significant for high-grade gliomas (CTV: P = 0.045; GTV: P = 0.044), while they were statistically insignificant for low-grade gliomas (CTV: P = 0.080; GTV: P = 0.117). The mean differences in the volumes for CTV and GTV were estimated to be -106.7% and -62.6%, respectively, taking the CT volumes as the baseline. Thus, even though, electron density information from CT is essential for RTP, target delineation during postoperative radiotherapy of brain tumors, especially for high-grade tumors, should be based on MRI so as to avoid inadvertent geographical misses, especially in the regions of peritumoral edema.