RESUMEN
Desmodium gangeticum (L.) belonging to family Fabaceae is an economically important medicinal plant which isutilised in Dashmoolarishta. Various bioactive compounds have been isolated from whole plant and roots, and one of them is an important phenolic compound - caffeic acid (CA). This phenolic acid and its derivatives have antioxidant, anti-inflammatory, anticarcinogenic and hepatocarcinoma, a highly aggressive and causing considerable mortality across the world. In the present study, leaf explants were placed on MS medium fortified with different concentration of cytokinin (BA/Kn) and auxin (IAA/NAA) for establishing callus cultures. MS medium fortified with BA (20 µM) and IAA (2 µM) was optimised for the same. Methanolic extracts of in vivo leaf sample (DG1) and in vitro sample (leaf derived callus) (DG2) were assessed for CA quantification using HPTLC. Thus, the chemical fingerprint that was obtained, confirmed that DG 2 of D. gangeticum exhibited the potency to synthesise more amount of CA (316 ± 7.5 µg/g DW) in comparison to DG1 which was 194 ± 2.3 µg/g DW.
RESUMEN
The lymphatic vasculature regulates lung homeostasis through drainage of fluid and trafficking of immune cells and plays a key role in the response to lung injury in several disease states. We have previously shown that lymphatic dysfunction occurs early in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) and that this is associated with increased thrombin and fibrin clots in lung lymph. However, the direct effects of CS and thrombin on lymphatic endothelial cells (LECs) in COPD are not entirely clear. Studies of the blood vasculature have shown that COPD is associated with increased thrombin after CS exposure that causes endothelial dysfunction characterized by changes in the expression of coagulation factors and leukocyte adhesion proteins. Here, we determined whether similar changes occur in LECs. We used an in vitro cell culture system and treated human lung microvascular lymphatic endothelial cells with cigarette smoke extract (CSE) and/or thrombin. We found that CSE treatment led to decreased fibrinolytic activity in LECs, which was associated with increased expression of plasminogen activator inhibitor 1 (PAI-1). LECs treated with both CSE and thrombin together had a decreased expression of tissue factor pathway inhibitor (TFPI) and increased expression of adhesion molecules. RNA sequencing of lung LECs isolated from mice exposed to CS also showed upregulation of prothrombotic and inflammatory pathways at both acute and chronic exposure time points. Analysis of publicly available single-cell RNA sequencing of LECs as well as immunohistochemical staining of lung tissue from COPD patients supported these data and showed increased expression of inflammatory markers in LECs from COPD patients compared to those from controls. These studies suggest that in parallel with blood vessels, the lymphatic endothelium undergoes inflammatory changes associated with CS exposure and increased thrombin in COPD. Further research is needed to unravel the mechanisms by which these changes affect lymphatic function and drive tissue injury in COPD.
RESUMEN
OBJECTIVE: It is unclear whether widespread use of biologics is reducing inflammatory bowel disease (IBD) surgical resection rates. We designed a population-based study evaluating the impact of early antitumour necrosis factor (TNF) on surgical resection rates up to 5 years from diagnosis. DESIGN: We evaluated all patients with IBD diagnosed in Cardiff, Wales 2005-2016. The primary measure was the impact of early (within 1 year of diagnosis) sustained (at least 3 months) anti-TNF compared with no therapy on surgical resection rates. Baseline factors were used to balance groups by propensity scores, with inverse probability of treatment weighting (IPTW) methodology and removing immortal time bias. Crohn's disease (CD) and ulcerative colitis (UC) with IBD unclassified (IBD-U) (excluding those with proctitis) were analysed. RESULTS: 1250 patients were studied. For CD, early sustained anti-TNF therapy was associated with a reduced likelihood of resection compared with no treatment (IPTW HR 0.29 (95% CI 0.13 to 0.65), p=0.003). In UC including IBD-U (excluding proctitis), there was an increase in the risk of colectomy for the early sustained anti-TNF group compared with no treatment (IPTW HR 4.6 (95% CI 1.9 to 10), p=0.001). CONCLUSIONS: Early sustained use of anti-TNF therapy is associated with reduced surgical resection rates in CD, but not in UC where there was a paradoxical increased surgery rate. This was because baseline clinical factors were less predictive of colectomy than anti-TNF usage. These data support the use of early introduction of anti-TNF therapy in CD whereas benefit in UC cannot be assessed by this methodology.