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Background/Aims@#Endoscopic mucosal resection (EMR) is the primary treatment for duodenal adenomas; however, it is associated with a high risk of perforation and bleeding, especially with larger lesions. The goal of this study was to demonstrate the feasibility and safety of endoscopic suturing (ES) for the closure of mucosal defects after duodenal EMR. @*Methods@#Consecutive adult patients who underwent ES of large mucosal defects after EMR of large (>2 cm) duodenal adenomas were retrospectively enrolled. The OverStitch ES system was employed for closing mucosal defects after EMR. Clinical outcomes and complications, including delayed bleeding and perforation, were documented. @*Results@#During the study period, ES of mucosal defects was performed in seven patients in eight sessions (six for prophylaxis and two for the treatment of perforation). All ES sessions were technically successful. No early or delayed post-EMR bleeding was recorded. In addition, no clinically obvious duodenal stricture or recurrence was encountered on endoscopic follow-up evaluation, and no patients required subsequent surgical intervention. @*Conclusions@#ES for the prevention and treatment of duodenal perforation after EMR is technically feasible, safe, and effective. ES should be considered an option for preventing or treating perforations associated with EMR of large duodenal adenomas.
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BACKGROUND: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments. OBJECTIVE: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aß)-induced microglial toxicity associated with the production of pro-inflammatory mediators. METHOD: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aß. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay. RESULTS: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1ß, IL-6 and TNF-α in Aß-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aß-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1ß, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators. CONCLUSIONS: These findings provided evidence that PS root extracts confer neuroprotection against Aß- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer's disease (AD).
Assuntos
Peptídeos beta-Amiloides/metabolismo , Citocinas/metabolismo , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Piper , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular Tumoral , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Microglia/metabolismo , Neuroproteção/efeitos dos fármacos , Neuroproteção/fisiologia , Raízes de Plantas , ProibitinasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum Roxb. (PS), belonging to Piperaceae family, is an edible plant with medicinal properties. It is traditionally used by the Malays to treat headache and boost memory. Pharmacological studies revealed that PS exhibits anti-inflammatory, anti-oxidant, anti-acetylcholinesterase, and anti-depressant-like effects. In view of this, the present study aimed to investigate the anti-inflammatory actions of PS and its potential neuroprotective effects against beta-amyloid (Aß)-induced microglia-mediated neurotoxicity. MATERIALS AND METHODS: The inhibitory effects of hexane (LHXN), dichloromethane (LDCM), ethyl acetate (LEA) and methanol (LMEOH) extracts from leaves of PS on Aß-induced production and mRNA expression of pro-inflammatory mediators in BV-2 microglial cells were assessed using colorimetric assay with Griess reagent, ELISA kit and real-time RT-PCR respectively. Subsequently, MTT reduction assay was used to evaluate the neuroprotective effects of PS leaf extracts against Aß-induced microglia-mediated neurotoxicity in SH-SY5Y neuroblastoma cells. The levels of tau proteins phosphorylated at threonine 231 (pT231) and total tau proteins (T-tau) were determined using ELISA kits. RESULTS: Polar extracts of PS leaves (LEA and LMEOH) reduced the Aß-induced secretion of pro-inflammatory cytokines (IL-1ß and TNF-α) in BV-2 cells by downregulating the mRNA expressions of pro-inflammatory cytokines. The inhibition of nitric oxide (NO) production could be due to the free radical scavenging activity of the extracts. In addition, conditioned media from Aß-induced BV-2 cells pre-treated with LEA and LMEOH protected SH-SY5Y cells against microglia-mediated neurotoxicity. Further mechanistic study suggested that the neuroprotective effects were associated with the downregulation of phosphorylated tau proteins. CONCLUSIONS: The present study suggests that polar extracts of PS leaves confer neuroprotection against Aß-induced microglia-mediated neurotoxicity in SH-SY5Y cells by attenuating tau hyperphosphorylation through their anti-inflammatory actions and could be a potential therapeutic agent for Alzheimer's disease.