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7 cells, which may suggest its anti-inflammatory activity.Osteoarthritis (OA) is marked by transcriptional factors. Twist-related protein 1 (TWIST-1) leads to the down-regulation of functional transcriptional regulators such as transforming growth factor-beta 1 (TGF-β1) and Wnt signals, thus blocking the growth and maturation of chondrocytes and providing new pathways to the production of therapeutic targets in OA therapy. Our research assesses the role of aberrant expressions TWIST1 and TGF-β1 as therapeutic targets in the regulation of osteoarthritis by treating with piperlongumine, a known biological agent. Monosodium iodoacetate (MIA) was administered to 32 male Wistar rats into their knee joints to provoke osteoarthritis. A week later, piperlongumine (PL) was orally administered to these rats for a duration of 28 days. AZ 960 The radiographic photos of these rats were documented. The histopathological and serum factors, namely interleukin-1beta (IL-1β), matrix metaloproteinases MMP-1 and MMP-3, were evaluated and their respective results were reported. RNA was extracted and real-time-PCR technique was optimized for TWIST1, TGF-1β and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) determination and sample values were recorded. When treated with PL at 100 mg/kg, our radiographic and histological studies revealed a substantial reduction of OA in rat models but no major improvements were observed at PL 50 mg/kg. Serum levels of IL-1β, MMP-1, and MMP-3 were greatly decreased when treated with PL 100 mg/kg. When administered with a dose higher than PL-100 mg/kg, the relative expressions of TWIST1, mRNA and TGF-β1 mRNA proteins were drastically reduced. Our results suggested that high-dose treatment with piperlongumine was beneficial and effective. TWIST1 and TGF-β1 aberrant expressions contributed as a new transcription factor function and supported the reduction of osteoarthritis intensity with piperlongumine therapy.Chronic epigastric pain syndrome (CEPS) is an important diagnostic problem, especially in patients without macroscopic and microscopic changes in gastric mucosa. The cause of this ailment is unclear. The aim of this study was the assessment of coexistence between symptoms of this syndrome and secretion level of dopamine (DA), as well as the efficacy of peripheral and central D2 receptors antagonist. Sixty depressive patients with CEPS occurring independently of the diet and with no Helicobacter pylori infection and 30 healthy subjects were enrolled in this study. Plasma DA and urinary homovanilic acid (HVA) concentration were measured by ELISA, and the mRNA expression of dopa decarboxylase (DDC) in gastric mucosa was evaluated by RT-PCR in 30 patients with CEPS and 30 controls. Severity of epigastric pain before and after 12 weeks 2 x 50 mg itopride or sulpiride treatment was evaluated using the modified 10-point Visual Analogue Scale. Higher average levels of plasma DA and urinary HVA levels in CEPS patients than controls 129.5 ± 22.0 versus 109.1 ± 18.4 pg/ml (p less then 0.001) and 6.82 ± 1.55 versus 5.39 ± 1.04 mg/24 h, respectively were obtained. Moreover, the expression of DDC in gastric mucosa of CEPS patients was higher than in healthy subjects (p less then 0.01). Sulpiride subsided epigastric pain in 73.3%, but itopride reduced it only in 6.6% of CEPS patients. We concluded that altered dopamine signalling may affect locally-and-centrally mediated chronic epigastric pain.Physical activity is crucial for maintaining health. Here we investigated the preconditioning effects of exercise on the vulnerability of gastric mucosa to ulcerogenic action of indomethacin (IM, 35 mg/kg, s.c.) or cold-restraint stressor (CR, 3 h, 10°C) in male rats. Single or repeated (5 days) training was used either voluntarily (2 h/day, wheel running) or in a forced way (treadmill). The intensity of the later was either "moderate" (9 m/min, 15 min) or "intensive" (15 m/min, 30 min). All protocols were confirmed by elevated plasma corticosterone and increased tail flick latencies (analgesia). IM-induced ulceration was attenuated by single intensive forced exercise, repeated voluntary and moderate forced exercise. On the contrary, single 2 h voluntary session aggravated the IM-induced ulceration. The ulcerogenic effect of CR was aggravated by single and repeated voluntary and single intensive forced exercise, while repeated moderate forced running was gastroprotective. Single moderate forced running did not influence the ulcerogenic effect of both agents. The results suggest that physical training might have both beneficial and harmful effects on the vulnerability of gastric mucosa to ulcerogenic stimuli depending on the nature of ulcerogenic stimulus as well as the intensity of running and its duration.The research focused on the diagnostic usefulness of urinary glycosaminoglycans excretion as new markers related to the ECM remodeling in the intestine. Their possible suitability in the diagnosis, differential diagnosis and treatment monitoring in the course of the two most common forms of inflammatory bowel diseases (IBD), i.e. ulcerative colitis (UC) and Crohn's disease (CD) were assessed in this study. Urinary excretion of total sulfated glycosaminoglycans (TGAG) and fraction of chondroitin sulfates (CS) were analysed in 47 patiens with IBD, including 31 patients with UC and 16 patients with CD at baseline and after one year of therapy. Sulfated GAGs excreted in urine were quantitated using standardized dye-binding method. A several-fold increase in urinary excretion of total GAG and CS fraction in both UC and CD patients compared to healthy subjects indicates the potential usefulness of quantitative urinary GAG analysis in the diagnosis of IBD. No differences were found in the amount of GAG excreted in the urine in patients with UC and CD. Adalimumab resulted in a decrease in the activity of the inflammatory process and the activity of the disease expressed in the Mayo scale, which was accompanied by an increase in the amount of CS excreted in the urine of UC patients. Moreover, significant correlation was found between Mayo scale and urinary total GAG and CS excretion in UC patients. The quantitative assessment of total glycosaminoglycans and chondroitin sulfates fraction in urine may be a marker helpful in the early diagnosis of IBD.
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