RESUMEN
OBJECTIVE: This study aimed to explore the specific function of M2 macrophages in intervertebral disc degeneration (IDD). METHODS: Intervertebral disc (IVD) samples from normal (n = 4) and IDD (n = 6) patients were collected, and the expression of M2-polarized macrophage marker, CD206, was investigated using immunohistochemical staining. Nucleus pulposus cells (NPCs) in a TNF-α environment were obtained, and a mouse caudal IVD puncture model was established. Mice with Rheb deletions, specifically in the myeloid lineage, were generated and subjected to surgery-induced IDD. IDD-induced damage and cell apoptosis were measured using histological scoring, X-ray imaging, immunohistochemical staining, and TdT-mediated dUTP nick end labeling (TUNEL) assay. Finally, mice and NPCs were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in IDD. RESULTS: Accumulation of CD206 in human and mouse IDD tissues was detected. Rheb deletion in the myeloid lineage (RheBcKO) increased the number of CD206+ M2-like macrophages (mean difference 18.6% [15.7-21.6%], P < 0.001), decreased cell apoptosis (mean difference -15.6% [-8.9 to 22.2%], P = 0.001) and attenuated the IDD process in the mouse IDD model. NPCs treated with Rspo2 displayed increased extracellular matrix catabolism and apoptosis; co-culture with a conditioned medium derived from RheBcKO mice inhibited these changes. Anti-Rspo2 treatment in the mouse caudal IVD puncture model exerted protective effects against IDD. CONCLUSIONS: Promoting CD206+ M2-like macrophages could reduce Rspo2 secretion, thereby alleviating experimental IDD. Rheb deletion may help M2-polarized macrophages accumulate and attenuate experimental IDD partially by inhibiting Rspo2 production. Hence, M2-polarized macrophages and Rspo2 may serve as therapeutic targets for IDD.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Ratones , Animales , Degeneración del Disco Intervertebral/patología , Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Apoptosis , Modelos Animales de Enfermedad , Macrófagos/metabolismoRESUMEN
Biosynthesis of gamma-aminobutyric acid (GABA) can be achieved by naturally occurring microorganisms with the advantages of cost-effectiveness and safety. In this study, Bacillus amyloliquefaciens EH-9 strain (B. amyloliquefaciens EH-9), a soil bacterium, was used to promote the accumulation of GABA in germinated rice seed. Further, the topical application of supernatant from rice seed co-cultivated with soil B. amyloliquefaciens EH-9 can significantly increase the production of type I collagen (COL1) in the dorsal skin of mice. The knocking down of the GABA-A receptor (GABAA) significantly reduced the production of COL1 in the NIH/3T3 cells and in the dorsal skin of mice. This result suggests that topical application of GABA can promote the biosynthesis of COL1 via its interaction with the GABAA receptor in the dorsal skin of mice. In summary, our findings illustrate for the first time that soil B. amyloliquefaciens EH-9 elicits GABA production in germinated rice seed to upregulate the formation of COL1 in the dorsal skin of mice. This study is translational because the result shows a potential remedy for skin aging by stimulating COL1 synthesis using biosynthetic GABA associated with B. amyloliquefaciens EH-9.
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Bacillus amyloliquefaciens , Oryza , Animales , Ratones , Regulación hacia Arriba , Colágeno Tipo I , Bacillus amyloliquefaciens/genética , Ácido gamma-Aminobutírico , Semillas , SueloRESUMEN
Balanoposthitis is a common inflammatory condition of male genitalia, while the overall microbiota spectrum and its relevance to contributing factors have yet to be determined. This case-control study included patients with balanoposthitis (n = 26) and matched healthy controls (n = 29), both uncircumcised. Overt fungal infection in balanoposthitis was excluded, swab samples were collected, 16S rRNA gene sequenced and analysed. The profile of the microbiome was further analysed in relation to the clinical severity of the disease and the physical barrier status of the glans penis, including mucosa pH, transepidermal water loss, and mucosa hydration. In general, the microbiota composition was similar between patients with balanoposthitis and healthy controls, while it was different between patients with balanoposthitis and healthy controls with redundant prepuce. Decreased hydration of the mucosa and increased pH were found in patients with balanoposthitis. Staphylococcus warneri and Prevotella bivia are the 2 most abundant balanoposthitis-associated species and are positively correlated with disease severity.
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Microbiota , Adulto , Estudios de Casos y Controles , Humanos , Inflamación/diagnóstico , Masculino , Membrana Mucosa , Pene , Prevotella , ARN Ribosómico 16S/genética , StaphylococcusRESUMEN
Collagen type I is a key structural component of dermis tissue and is produced by fibroblasts and the extracellular matrix. The skin aging process, which is caused by intrinsic or extrinsic factors, such as natural aging or free radical exposure, greatly reduces collagen expression, thereby leading to obstructed skin elasticity. We investigated the effective fermentation of Cetearyl isononanoate (CIN), a polyethylene glycol (PEG) analog, as a carbon source with the skin probiotic bacterium Staphylococcus epidermidis (S.epidermidis) or butyrate, as their fermentation metabolites could noticeably restore collagen expression through phosphorylated extracellular signal regulated kinase (p-ERK) activation in mouse fibroblast cells and skin. Both the in vitro and in vivo knockdown of short-chain fatty acid (SCFA) or free fatty acid receptor 2 (FFaR2) considerably blocked the probiotic effect of S. epidermidis on p-ERK-induced collagen type I induction. These results demonstrate that butyric acid (BA) in the metabolites of fermenting skin probiotic bacteria mediates FFaR2 to induce the synthesis of collagen through p-ERK activation. We hereby imply that metabolites from the probiotic S. epidermidis fermentation of CIN as a potential carbon source could restore impaired collagen in the dermal extracellular matrix (ECM), providing integrity and elasticity to skin.
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Ácido Butírico/metabolismo , Colágeno Tipo I/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Probióticos , Receptores Acoplados a Proteínas G/metabolismo , Envejecimiento de la Piel/efectos de los fármacos , Staphylococcus epidermidis/fisiología , Animales , Colágeno Tipo I/efectos de los fármacos , Matriz Extracelular/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/genética , Ácidos Grasos Volátiles/metabolismo , Femenino , Fermentación , Fibroblastos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Fosforilación , Receptores Acoplados a Proteínas G/genética , Piel/metabolismo , Piel/microbiologíaRESUMEN
Electrogenic bacteria can mediate electron transfer to conserve energy and promote growth. To examine bacterial electrogenicity, an L. mesenteroides EH-1 strain was cultured in rich media in the presence and absence of 2% glucose. After 12 h incubation, glucose triggered fermentation of L. mesenteroides EH-1 to produce >10 mmol/l acetate and elicit electricity measured by voltage changes. The electricity production was mediated by glucose fermentation since pre-treatment of L. mesenteroides EH-1 with furfural, a fermentation inhibitor, completely diminished the voltage increases. The deficiency of furfural pre-treated L. mesenteroides EH-1 in electricity production can be restored by the external addition of acetate into the bacterial culture, suggesting the function of acetate as an electron donor. Oral administration of HFD-fed mice with L. mesenteroides EH-1 in the presence or absence of glucose significantly attenuated the high level of pro-inflammatory IL-6 cytokine in blood. Bacterial electricity can be elicited by fermentation. Supplementation of fermenting and electrogenic L. mesenteroides EH-1 may provide a novel approach for the reduction of pro-inflammatory IL-6 cytokine that increased in chronic inflammation, autoimmune diseases, cancers, and infections.
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Electricidad , Fermentación/fisiología , Microbiología de Alimentos/métodos , Glucosa/metabolismo , Interleucina-6/sangre , Leuconostoc mesenteroides/metabolismo , Leuconostoc mesenteroides/fisiología , Acetatos/farmacología , Administración Oral , Animales , Dieta Alta en Grasa , Femenino , Furaldehído/farmacología , Leuconostoc mesenteroides/efectos de los fármacos , RatonesRESUMEN
Uremic pruritus with elevated levels of calcium phosphate (CaP) in skin is a common symptom in patients with chronic kidney disease (CKD). In this study, we demonstrate that intradermal injection of CaP into mice triggered scratching by up-regulating the IL-6 in skin and phosphorylation of ERKs in dorsal root ganglion (DRG) in a dose-dependent manner. IL-6 is essential because the CaP-induced up-regulation of phosphorylated (p)-ERK in DRG was considerably reduced in the IL-6 knockout mice. Microarray analysis in conjunction with real-time PCR revealed a higher mRNA expression of Bruton's tyrosine kinase (BTK) gene in DRG after CaP injection. The inhibition of BTK by ibrutinib noticeably diminish the CaP-induced up-regulation of IL-6 and p-ERK in mice. A high amount of IL-6 was detected in itchy skin and blood of patients with CKD. The expressions of p-BTK and p-ERK in DRG primary cells reached maximum levels at 1 and 10 min, respectively, after treatment of recombinant IL-6 and were significantly reduced by treatment of IL-6 along with ibrutinib. The mechanism by which the CaP-induced pruritus mediated by the IL-6/p-BTK/p-ERK signaling was revealed.-Keshari, S., Sipayung, A. D., Hsieh, C.-C., Su, L.-J., Chiang, Y.-R., Chang, H.-C., Yang, W.-C., Chuang, T.-H., Chen, C.-L., Huang, C.-M. IL-6/p-BTK/p-ERK signaling mediates calcium phosphate-induced pruritus.
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Agammaglobulinemia Tirosina Quinasa/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ganglios Espinales/metabolismo , Interleucina-6/metabolismo , Prurito/metabolismo , Adenina/análogos & derivados , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Agammaglobulinemia Tirosina Quinasa/genética , Animales , Fosfatos de Calcio , Quinasas MAP Reguladas por Señal Extracelular/genética , Femenino , Ganglios Espinales/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Interleucina-6/genética , Interleucina-6/farmacología , Ratones Endogámicos C57BL , Ratones Noqueados , Fosforilación/efectos de los fármacos , Piperidinas , Prurito/inducido químicamente , Prurito/genética , Pirazoles/farmacología , Pirimidinas/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patologíaRESUMEN
The probiotic activity of skin Staphylococcus epidermidis (S. epidermidis) bacteria can elicit diverse biological functions via the fermentation of various carbon sources. Here, we found that polyethylene glycol (PEG)-8 Laurate, a carbon-rich molecule, can selectively induce the fermentation of S. epidermidis, not Cutibacterium acnes (C. acnes), a bacterium associated with acne vulgaris. The PEG-8 Laurate fermentation of S. epidermidis remarkably diminished the growth of C. acnes and the C. acnes-induced production of pro-inflammatory macrophage-inflammatory protein 2 (MIP-2) cytokines in mice. Fermentation media enhanced the anti-C. acnes activity of a low dose (0.1%) clindamycin, a prescription antibiotic commonly used to treat acne vulgaris, in terms of the suppression of C. acnes colonization and MIP-2 production. Furthermore, PEG-8 Laurate fermentation of S. epidermidis boosted the activity of 0.1% clindamycin to reduce the sizes of C. acnes colonies. Our results demonstrated, for the first time, that the PEG-8 Laurate fermentation of S. epidermidis displayed the adjuvant effect on promoting the efficacy of low-dose clindamycin against C. acnes. Targeting C. acnes by lowering the required doses of antibiotics may avoid the risk of creating drug-resistant C. acnes and maintain the bacterial homeostasis in the skin microbiome, leading to a novel modality for the antibiotic treatment of acne vulgaris.
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Clindamicina/administración & dosificación , Lauratos/metabolismo , Polietilenglicoles/metabolismo , Propionibacteriaceae/efectos de los fármacos , Staphylococcus epidermidis/metabolismo , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/microbiología , Animales , Antibacterianos/administración & dosificación , Fermentación , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Técnicas In Vitro , Ratones , Ratones Endogámicos ICR , Probióticos/metabolismo , Propionibacteriaceae/crecimiento & desarrollo , Propionibacterium acnes/efectos de los fármacos , Propionibacterium acnes/crecimiento & desarrollo , Piel/efectos de los fármacos , Piel/metabolismo , Piel/microbiologíaRESUMEN
The glycerol fermentation of probiotic Staphylococcus epidermidis (S. epidermidis) in the skin microbiome produced butyric acid in vitro at concentrations in the millimolar range. The exposure of dorsal skin of mice to ultraviolet B (UVB) light provoked a significant increased production of pro-inflammatory interleukin (IL)-6 cytokine. Topical application of butyric acid alone or S. epidermidis with glycerol remarkably ameliorated the UVB-induced IL-6 production. In vivo knockdown of short-chain fatty acid receptor 2 (FFAR2) in mouse skin considerably blocked the probiotic effect of S. epidermidis on suppression of UVB-induced IL-6 production. These results demonstrate that butyric acid in the metabolites of fermenting skin probiotic bacteria mediates FFAR2 to modulate the production of pro-inflammatory cytokines induced by UVB.
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Ácido Butírico/farmacología , Interleucina-6/metabolismo , Microbiota/efectos de los fármacos , Probióticos/farmacología , Receptores Acoplados a Proteínas G/metabolismo , Piel/microbiología , Staphylococcus epidermidis/química , Rayos Ultravioleta , Acetolactato Sintasa/metabolismo , Animales , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/efectos de la radiación , Ácidos Grasos Volátiles/metabolismo , Femenino , Fermentación , Glicerol/farmacología , Inflamación/patología , Ratones Endogámicos ICR , Microbiota/efectos de la radiación , Piel/efectos de los fármacos , Piel/patología , Piel/efectos de la radiaciónRESUMEN
BACKGROUND: To compare the acute gastrointestinal (GI) and genitourinary (GU) toxicity profiles between intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in rectal cancer patients treated with neoadjuvant chemoradiation (NCRT) using meta-analysis and pooled-analysis from published articles. METHODS: Literature search was performed in PubMed and EMBASE from inception to March 2017. The odd ratios (ORs) were calculated and random effects model was used for meta-analysis. Chi-square or Fisher's exact test was performed for the pooled-analysis. RESULTS: Six studies including a total of 859 patients met the inclusion criteria. Most patients (98.7%) received NCRT. In the meta-analysis, IMRT reduced grade ≥ 2 acute overall GI toxicity, diarrhea and proctitis with ORs of 0.38, 0.32 and 0.60, respectively (all P < 0.05), compared to 3DCRT. IMRT also reduced acute grade ≥ 3 proctitis compared to 3D-CRT (OR, 0.24; P = 0.03). No significant heterogeneity or publication bias was detected. In the pooled-analysis, IMRT reduced the incidence of grade ≥ 2 acute overall GI toxicity, diarrhea, proctitis and GU toxicity (all P < 0.05). Moreover, lower incidence of grade ≥ 3 acute overall GI toxicity, diarrhea and proctitis were observed in the patients treated with IMRT (all P < 0.05). CONCLUSIONS: IMRT significantly reduced acute toxicity in locally advanced rectal cancer patients treated with NCRT compared to 3DCRT.
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Quimioradioterapia/efectos adversos , Terapia Neoadyuvante/efectos adversos , Radioterapia Conformacional/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , Neoplasias del Recto/radioterapia , Anciano , Quimioradioterapia/métodos , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Radioterapia Conformacional/métodos , Radioterapia de Intensidad Modulada/métodos , Neoplasias del Recto/patologíaRESUMEN
Antibiotics without selectivity for acne treatment may destroy the beneficial microbes in the human microbiome that helps to fight Cutibacterium acnes (C. acnes), a bacterium associated with inflammatory acne vulgaris. Probiotic treatment by direct application of live Staphylococcus epidermidis (S. epidermidis) onto the open acne lesions may run the risk of bloodstream infections. Here, we fabricated the polysulfone microtube array membranes (PSF MTAM) to encapsulate probiotic S. epidermidis. We demonstrate that the application of the encapsulation of S. epidermidis in PSF MTAM enhanced the glycerol fermentation activities of S. epidermidis. To mimic the granulomatous type of acne inflammatory acne vulgaris, the ears of mice were injected intradermally with C. acnes to induce the secretion of macrophage inflammatory protein-2 (MIP-2), a murine counterpart of human interleukin (IL)-8. The C. acnes-injected mouse ears were covered with a PST MTAM encapsulated with or without S. epidermidis in the presence of glycerol. The application of S. epidermidis-encapsulated PST MTAM plus glycerol onto the C. acnes-injected mouse ears considerably reduced the growth of C. acnes and the production of MIP-2. Furthermore, no S. epidermidis leaked from PSF MTAM into mouse skin. The S. epidermidis-encapsulated PST MTAM functions as a probiotic acne patch.
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Antibiosis , Probióticos , Propionibacteriaceae/fisiología , Piel/microbiología , Staphylococcus epidermidis/fisiología , Animales , Quimiocina CXCL2/metabolismo , Dermatitis/metabolismo , Dermatitis/microbiología , Fermentación , Glicerol/metabolismo , Humanos , RatonesRESUMEN
Unlike USA300, a strain of community-acquired methicillin-resistant Staphylococcus aureus (MRSA), commensal Staphylococcus aureus (S. aureus) bacteria isolated from human skin demonstrated the ability to mediate the glycerol fermentation to produce short-chain fatty acids (SCFAs). Quantitative proteomic analysis of enzymes involved in glycerol fermentation demonstrated that the expression levels of six enzymes, including glycerol-3-phosphate dehydrogenase (GPDH) and phosphoglycerate mutase (PGM), in commensal S. aureus are more than three-fold higher than those in USA300. Western blotting validated the low expression levels of GPDH in USA300, MRSA252 (a strain of hospital-acquired MRSA), and invasive methicillin-susceptible S. aureus (MSSA). In the presence of glycerol, commensal S. aureus effectively suppressed the growth of USA300 in vitro and in vivo. Active immunization of mice with lysates or recombinant α-hemolysin of commensal S. aureus or passive immunization with neutralizing sera provided immune protection against the skin infection of USA300. Our data illustrate for the first time that commensal S. aureus elicits both innate and adaptive immunity via glycerol fermentation and systemic antibody production, respectively, to fight off the skin infection of pathogenic MRSA.
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Staphylococcus aureus Resistente a Meticilina/inmunología , Microbiota/inmunología , Infecciones Cutáneas Estafilocócicas/inmunología , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Células Cultivadas , Femenino , Glicerol/metabolismo , Glicerolfosfato Deshidrogenasa/genética , Glicerolfosfato Deshidrogenasa/metabolismo , Inmunización Pasiva , Ratones , Ratones Endogámicos ICR , Fosfoglicerato Mutasa/genética , Fosfoglicerato Mutasa/metabolismo , Piel/inmunología , Piel/microbiología , Infecciones Cutáneas Estafilocócicas/prevención & controlRESUMEN
BACKGROUND: Platinum resistance enhances DNA damage repair through nucleotide excision repair mechanisms involving the excision repair cross-complementing group 1 (ERCC1), X-ray cross-complementing group 1 (XRCC1), and excision repair cross-complementing group 2 (ERCC2). We evaluated the correlation between the expression of these three DNA repair genes and clinical outcomes in patients with rectal cancer receiving FOLFOX-based preoperative chemoradiotherapy (CRT). METHODS: Using immunohistochemistry, we examined the expression of ERCC1, ERCC2, and XRCC1 in pre-CRT cancer tissues from 86 patients with rectal cancer who had undergone curative resection and preoperative CRT with FOLFOX-4 to identify potential predictors of clinical outcomes. RESULTS: Following CRT, 57 and 29 patients were classified as responders (pathological tumor regression grade TRG 0 and TRG 1) and poor responders (TRG 2 and TRG 3), respectively. The multivariate analysis revealed that ERCC1 overexpression was correlated with a poor CRT response [p < 0.0001; odds ratio (OR), 9.397; 95% confidence interval (CI) 2.721-32.457]. Furthermore, a poor response to CRT (pathological TRG of 2-3) (p = 0.18; OR 5.685; 95% CI 1.349-23.954) and abnormal pre-CRT serum carcinoembryonic antigen levels (>5 ng/mL) (p = 0.03; OR 6.288; 95% CI 1.198-33.006) were independent predictors of postoperative relapse. By contrast, ERCC2 and XRCC1 expression did not play predictive roles in the analyzed patients. CONCLUSIONS: ERCC1 overexpression is associated with a poor preoperative CRT response in patients with rectal cancer receiving FOLFOX-based preoperative CRT. ERCC1 is a potential biomarker for identifying patients who can benefit from customized treatment programs.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia Adyuvante , Proteínas de Unión al ADN/metabolismo , Endonucleasas/metabolismo , Neoplasias del Recto/metabolismo , Neoplasias del Recto/terapia , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/metabolismo , Proteína de la Xerodermia Pigmentosa del Grupo D/metabolismo , Adulto , Anciano , Femenino , Fluorouracilo/uso terapéutico , Humanos , Inmunohistoquímica , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Neoplasias del Recto/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: After a low anterior resection, creating a defunctioning stoma is vital for securing the anastomosis in low-lying rectal cancer patients receiving concurrent chemoradiotherapy. Although it decreases the complication and reoperation rates associated with anastomotic leakage, the complications that arise before and after stoma closure should be carefully evaluated and managed. METHODS: This study enrolled 95 rectal cancer patients who received neoadjuvant concurrent chemoradiotherapy and low anterior resection with anastomosis of the bowel between July 2010 and November 2012. A defunctioning stoma was created in 63 patients during low anterior resection and in another three patients after anastomotic leakage. RESULTS: The total complication rate from stoma creation to closure was 36.4%. Ileostomy led to greater renal insufficiency than colostomy did and significantly increased the readmission rate (all p < 0.05). The complication rate related to stoma closure was 36.0%. Patients with ileostomy had an increased risk of developing complications (p = 0.017), and early closure of the defunctioning stoma yielded a higher incidence of morbidity (p = 0.006). Multivariate analysis revealed that a time to closure of ≤109 days was an independent risk factor for developing complications (p = 0.007). CONCLUSIONS: The optimal timing of stoma reversal is at least 109 days after stoma construction in rectal cancer patients receiving concurrent chemoradiotherapy and low anterior resection.
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Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/etiología , Quimioradioterapia/efectos adversos , Ileostomía/efectos adversos , Complicaciones Posoperatorias , Neoplasias del Recto/terapia , Estomas Quirúrgicos/efectos adversos , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/patología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The robotic system has advantages of high-definition three-dimensional vision and articular instruments with high dexterity, allowing more precise dissection in the deep and narrow pelvic cavity. METHODS: We enrolled 95 patients with stage I-III rectal cancer (adenocarcinoma) who underwent totally robotic-assisted total mesorectal excision (TME) with single-docking technique at a single institution between September 2013 and December 2016. RESULTS: Of the 95 patients, 48 (50.5%) and 30 (31.6%) patients had lower and middle rectal cancers, respectively. Of the 75 (78.9%) patients undergoing preoperative concurrent chemoradiotherapy (CCRT), 27 (28.4%) exhibited pathologic complete response (pCR). Only four (4.2%) patients underwent abdominoperineal resection and the sphincter preservation rate was 95.8%. R0 resection was performed in 92 (96.8%) patients. Circumferential resection margin (CRM) and distal resection margin (DRM) were positive in 2 (2.1%) and 1 (1.1%) patients, respectively. The anastomotic leakage rate was 5.4% (5/95 patients). The overall complication rate was 17.9% (17/95 patients); most of them were mild. No 30-day hospital mortality occurred, and no patients required conversion to open surgery. In 92 patients undergoing R0 resection, 2-year overall survival was 94% and 2-year disease-free survival was 83%. CONCLUSIONS: The results demonstrated that totally robotic-assisted TME with the single-docking technique is safe and feasible for patients with rectal cancer, with or without preoperative CCRT. Moreover, favorable pCR rate, R0 resection rate, CRM, DRM, sphincter preservation rate, and short-term oncological outcomes can be achieved by combining this approach with appropriate preoperative CCRT.
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Adenocarcinoma/cirugía , Neoplasias del Recto/cirugía , Recto/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Neoplasias del Recto/mortalidad , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/instrumentación , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Chewing areca nut is closely associated with oral squamous cell carcinoma (OSCC). The current study aimed to investigate potential associations between areca nut extract (ANE) and cisplatin toxicity in OSCC cells. OSCC cells (Cal-27 and Scc-9) viability and apoptosis were analyzed after treatment with ANE and/or cisplatin. The expressions of proteins associated with autophagy and the AMP-activated protein kinase (AMPK) signaling network were evaluated. We revealed that advanced OSCC patients with areca nut chewing habits presented higher LC3 expression and poorer prognosis. Reactive oxygen species (ROS)-mediated autophagy was induced after pro-longed treatment of ANE (six days, 3 µg). Cisplatin toxicity (IC50, 48 h) was decreased in OSCC cells after ANE treatment (six days, 3 µg). Cisplatin toxicity could be enhanced by reversed autophagy by pretreatment of 3-methyladenine (3-MA), N-acetyl-l-cysteine (NAC), or Compound C. Cleaved-Poly-(ADP-ribose) polymerase (cl-PARP) and cleaved-caspase 3 (cl-caspase 3) were downregulated in ANE-treated OSCC cells in the presence of cisplatin, which was also reversed by NAC and Compound C. Collectively, ANE could decrease cisplatin toxicity of OSCC by inducing autophagy, which involves the ROS and AMPK/mTOR signaling pathway.
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Proteínas Quinasas Activadas por AMP/metabolismo , Areca/química , Autofagia/efectos de los fármacos , Cisplatino/farmacología , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cisplatino/toxicidad , Resistencia a Antineoplásicos , Humanos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Modelos Biológicos , Neoplasias de la Boca/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
PURPOSE: We present the preliminary experiences with and short-term outcomes of 50 consecutive patients with rectal cancer who underwent preoperative concurrent chemoradiotherapy (CCRT) followed by robotic surgery by using the high dissection and low ligation technique. METHODS: Between October 2013 and August 2015, 50 patients with rectal cancer underwent robotic surgery after preoperative CCRT at a single institution. We performed D3 lymph node dissection and low tie ligation of the inferior mesenteric artery (IMA); this technique is referred to as the high dissection and low ligation technique. Clinicopathological features, perioperative parameters, and postoperative outcomes were retrospectively analyzed. RESULTS: FOLFOX regimen was used for preoperative CCRT in 26 (52 %) patients. Long-course radiotherapy was concurrently administered. A pathological complete response (pCR) was obtained in 14 (28 %) patients. Of the 50 patients, 23 (46 %) patients received intersphincteric resection (ISR) with coloanal anastomosis, 25 (50 %) patients received lower anterior resection (LAR), and 2 (4 %) patients received abdominoperineal resection (APR). Apical nodes were pathologically harvested in 47 (94 %) patients, and the median number of harvested apical lymph nodes was 2 (range, 0-10). The overall complication rate was 24 % (10 patients with 12 episodes), and most complications were mild. CONCLUSION: Roboic rectal surgery combined with appropriate preoperative CCRT helps in achieving a favorable pCR, circumferential resection margin, and sphincter preservation. Moreover, high dissection and low ligation of the IMA can be safely performed using the da Vinci(®) Surgical System safely which yield favorable short-term clinical outcomes.
Asunto(s)
Quimioradioterapia , Disección , Ligadura/métodos , Cuidados Preoperatorios , Neoplasias del Recto/terapia , Procedimientos Quirúrgicos Robotizados/métodos , Adulto , Anciano , Anciano de 80 o más Años , Cirugía Colorrectal , Femenino , Humanos , Curva de Aprendizaje , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tempo Operativo , Atención Perioperativa , Cuidados Posoperatorios , Complicaciones Posoperatorias/etiología , Neoplasias del Recto/cirugía , Resultado del TratamientoRESUMEN
Carbon monoxide (CO) poisoning from natural gas water heaters is a common household accident in Taiwan. We propose a wireless and batteryless intelligent CO sensor for improving the safety of operating natural gas water heaters. A micro-hydropower generator supplies power to a CO sensor without battery (COSWOB) (2.5 W at a flow rate of 4.2 L/min), and the power consumption of the COSWOB is only ~13 mW. The COSWOB monitors the CO concentration in ambient conditions around natural gas water heaters and transmits it to an intelligent gateway. When the CO level reaches a dangerous level, the COSWOB alarm sounds loudly. Meanwhile, the intelligent gateway also sends a trigger to activate Wi-Fi alarms and sends notifications to the mobile device through the Internet. Our strategy can warn people indoors and outdoors, thereby reducing CO poisoning accidents. We also believe that our technique not only can be used for home security but also can be used in industrial applications (for example, to monitor leak occurrence in a pipeline).
RESUMEN
Acne dysbiosis happens when there is a microbial imbalance of the over-growth of Propionibacterium acnes (P. acnes) in the acne microbiome. In our previous study, we demonstrated that Staphylococcus epidermidis (S. epidermidis, a probiotic skin bacterium) can exploit glycerol fermentation to produce short-chain fatty acids (SCFAs) which have antimicrobial activities to suppress the growth of P. acnes. Unlike glycerol, sucrose is chosen here as a selective fermentation initiator (SFI) that can specifically intensify the fermentation activity of S. epidermidis, but not P. acnes. A co-culture of P. acnes and fermenting S. epidermidis in the presence of sucrose significantly led to a reduction in the growth of P. acnes. The reduction was abolished when P. acnes was co-cultured with non-fermenting S. epidermidis. Results from nuclear magnetic resonance (NMR) analysis revealed four SCFAs (acetic acid, butyric acid, lactic acid, and succinic acid) were detectable in the media of S. epidermidis sucrose fermentation. To validate the interference of S. epidermidis sucrose fermentation with P. acnes, mouse ears were injected with both P. acnes and S. epidermidis plus sucrose or phosphate buffered saline (PBS). The level of macrophage-inflammatory protein-2 (MIP-2) and the number of P. acnes in ears injected with two bacteria plus sucrose were considerably lower than those in ears injected with two bacteria plus PBS. Our results demonstrate a precision microbiome approach by using sucrose as a SFI for S. epidermidis, holding future potential as a novel modality to equilibrate dysbiotic acne.
Asunto(s)
Acné Vulgar/terapia , Antibiosis , Disbiosis/terapia , Fermentación/efectos de los fármacos , Probióticos/farmacología , Staphylococcus epidermidis/efectos de los fármacos , Sacarosa/farmacología , Acné Vulgar/microbiología , Acné Vulgar/patología , Animales , Carga Bacteriana/efectos de los fármacos , Biomarcadores/metabolismo , Quimiocina CXCL2/genética , Quimiocina CXCL2/metabolismo , Técnicas de Cocultivo , Disbiosis/microbiología , Disbiosis/patología , Oído/microbiología , Oído/patología , Femenino , Expresión Génica , Glicerol/metabolismo , Glicerol/farmacología , Humanos , Ratones , Ratones Endogámicos ICR , Microbiota , Probióticos/metabolismo , Propionibacterium acnes/efectos de los fármacos , Propionibacterium acnes/crecimiento & desarrollo , Propionibacterium acnes/patogenicidad , Piel/efectos de los fármacos , Piel/microbiología , Piel/patología , Staphylococcus epidermidis/crecimiento & desarrollo , Staphylococcus epidermidis/metabolismo , Sacarosa/metabolismoRESUMEN
PURPOSE: Bone marrow-derived cells (BMDCs) for clinical transplantation were carried out many years in treating spinal cord injury (SCI) without a clear conclusion. This study aimed to evaluate the safety and efficacy of BMDC transplantation in treatment of SCI patients. METHOD: Electronic databases, including PubMed, EMBASE, MEDLINE, and the Cochrane library, were searched to identify clinical therapeutic trials studying the application of BMDC transplantation in SCI. RESULTS: Overall the quality of the 24 studies was low, including one Grade I level of evidence, six Grade II levels, three Grade III levels, and 14 Grade IV levels. With a maximum of six-yr follow-up, the procedure-related complications were minor and temporary, without serious adverse events (p = 0, n = 594). AIS improvement rate was analyzed in favor of BMDCs 6.13 (95% CI, 3.0-12.51; p < 0.001). In patient with complete (AIS A) and chronic SCI, the application of cell transplantation numbers between n × (10(7) -10(8) ) seemed to be more beneficial (p < 0.05 for all groups). CONCLUSIONS: Based on short-medium terms following up, BMDC transplantation appears to be safe and valid in SCI patients, more effective in chronic and complete injury. Nonetheless, prospective, randomized trials in larger cohorts are still needed.
Asunto(s)
Trasplante de Médula Ósea , Traumatismos de la Médula Espinal/cirugía , Trasplante de Células Madre , Ensayos Clínicos como Asunto , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: SMAD3, which is accumulated in the nucleus, transcriptionally regulates TGF-ß target genes, playing a significant role in mediating the activities of TGF-ß. In this study, we assessed the roles of TGF-ß1, SMAD3, and phosphorylated SMAD3 expressions in patients with locally advanced rectal cancer following preoperative fluoropyrimidine-based chemoradiotherapy. METHODS: Using immunohistochemistry, we examined TGF-ß1, SMAD3, and phosphorylated SMAD3 expressions in pre-chemoradiotherapy cancer tissues from 86 locally advanced rectal cancer patients. After chemoradiotherapy, 64 of 86 (74.4 %) locally advanced rectal cancer patients were classified as responders (pathological tumor regression grades of 2-4). RESULTS: A multivariate analysis showed that phosphorylated SMAD3 overexpression correlated to poor preoperative chemoradiotherapy responses (P = 0.015; OR 7.218; 95 % CI 1.479-35.229). Furthermore, a poor response (pathological tumor regression grades of 0-1) was an independent predictor of postoperative relapse (P = 0.021; OR 5.452; 95 % CI 1.286-23.113). Additionally, patients with phosphorylated SMAD3 overexpression were found to have a worse disease-free survival (P = 0.023). CONCLUSIONS: Our data suggested that analyzing pre-chemoradiotherapy tumors for phosphorylated SMAD3 overexpression would assist physicians in identifying locally advanced rectal cancer patients who may have a poor response risk to preoperative fluoropyrimidine-based chemoradiotherapy.