RESUMO
Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor's phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.
Assuntos
Melanoma , Animais , Feminino , Humanos , Células Endoteliais/metabolismo , Macrófagos/metabolismo , Melanoma/metabolismo , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Microambiente Tumoral , CamundongosRESUMO
BACKGROUND/PURPOSE: Clarithromycin-based standard triple therapy is still commonly adopted by 81.4% of physicians in real-world practice but yields low eradication rates. Therefore, we conducted this study to compare the efficacy of gastric juice-guided therapy for first-line eradication with the standard triple therapy, in order to provide an alternative to real-world practice. METHODS: A total of 182 treatment-naïve Hp-infected patients were included and randomly allocated to either susceptibility-guided therapy (SGT) with gastric juice PCR or Clarithromycin-based standard triple therapy (STT) for 7 days. RESULTS: The intention-to-treat eradication rates were 89% (81/91) in SGT and 75.8% in STT (p < 0.031). The per-protocol eradication rates were 91.0% (81/89) in SGT and 79.3% (69/87) in STT (p < 0.034). Among the subgroups of different antibiotic resistance, patients with SGT demonstrated superior eradication rates (91.7% vs 45.5%, p < 0.027) in the subgroup of both clarithromycin resistance and levofloxacin resistance. CONCLUSION: This prospective randomized controlled trial demonstrated the reliable efficacy of susceptibility-guided therapy via gastric juice PCR for the first-line Hp eradication. In Asia-Pacific area, where standard triple therapy is still adopted by the majority of the physicians, it is a recommended alternative to overcome the increasing antibiotic resistance.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Quimioterapia Combinada , Suco Gástrico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/genética , Humanos , Reação em Cadeia da Polimerase , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
RATIONALE: Melamine is ubiquitously present in our daily life. It has a known effect on the kidneys, but it may also adversely affect the reproduction system. We have developed an analytical method for measuring melamine levels in maternal placenta and correlated these levels with melamine concentrations in urine, a necessary step in finding out if melamine might cross the placenta and enter the circulation of the fetus. METHODS: We used liquid-liquid extraction, clean up by solid-phase extraction (SPE), and isotope-dilution liquid chromatography/tandem mass spectrometry (LC/MS/MS) to measure melamine in placenta specimens. The results of this method were assessed for linearity, limits of quantitation (LOQs), and intra- and inter-assay precision as well as accuracy, matrix effect, and recovery rate. RESULTS: Calibration curves indicated good linearity (r >0.995) over concentrations ranging from 5 to 500 ng/mL in placenta specimens, intra- and inter-assay precision from 0.89% to 27.07%, and accuracy from 92.4% to123.5%. Recovery ranged from 63.9 to 83.9%, and the LOQ was 5 ng/mL in placenta (0.2 g). Placental melamine levels ranged from 7.87 to19.64 ng/mL, all detectable (n = 8). Pregnant women with higher levels of urinary melamine had higher placenta melamine levels than those with non-detectable urinary melamine, though the results were not significantly different (p = 0.149, n = 4 in each group). CONCLUSIONS: The results of this study suggest that pregnant women were exposed to low doses of melamine in their daily lives as measured in urine samples and placenta specimens. It is unclear whether placenta melamine concentrations can better represent long-term exposure than urine or whether melamine in the uterus can enter the fetus via this route.
Assuntos
Placenta/química , Espectrometria de Massas em Tandem/métodos , Triazinas/análise , Cromatografia Líquida/métodos , Feminino , Humanos , Limite de Detecção , Microextração em Fase Líquida/métodos , Gravidez , Extração em Fase Sólida/métodos , Triazinas/urinaRESUMO
The incidence and prevalence of inflammatory bowel disease have been increasing for decades and IBD has become a worldwide disease. Epidemiology studies demonstrated higher incidence rates in the more westernized countries. The change of habitual diets in these countries is perceived as the reason for the development of IBD. Besides, molecular biological studies showed some pathogenic substances produced after digestion of daily diet decrease the diversity of intestinal microbiota and cause dysbiosis of microbiome. Then, chronic inflammation occurs in some genetically susceptible subjects and IBD developed. As a result, many researchers started to investigate the potential therapeutic effects of nutrients and dietary intervention on the clinical course and pathogenesis of IBD. Carbohydrates, fats, proteins and fibers are investigated and their molecular roles in the inflammatory process are discovered gradually. The undigested carbohydrates are proved to cause overgrowth of colonic bacteria and inflammation occurs by altering colonic microbiome. ω-3 poly-unsaturated fatty acids are more favored over ω-6 poly-unsaturated fatty acids due to its less pro-inflammatory properties. High fibers produce more short-chain fatty acids in colon and facilitate the diversity of colonic microbiota. Moreover, some dietary interventions were designed and studied with promising results. Low FODMAP is recommended in IBS and is also suggested in patients of IBD with IBS-like symptoms. Specific Carbohydrate Diet was designed for celiac disease at first and is proved to be effective to decrease inflammation and to induce remission by decreasing non-digested carbohydrates into colon. Exclusive Enteral Nutrition has been investigated and is suggested to be the first line of management in pediatric CD in many literatures. Paleolithic diet and semi-vegetarian diet are evaluated and might be beneficial in some clinical settings. These findings are promising but limited to the evidence without high quality level. Some more well-designed studies with randomization and double-blind are needed and the primary endpoints should be more focused on the decrease of inflammation in pathology and mucosal healing in endoscopy instead of relief of the symptoms.
Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Dieta , Método Duplo-Cego , Disbiose , Humanos , Estado NutricionalRESUMO
BACKGROUND: Culture of Helicobacter pylori with previous eradication failure has been emphasized in clinical guidelines. The current unmet need to manage previously treated H pylori is one tool with diagnostic accuracy and ability for antibiotics susceptibility. Gastric juice PCR can provide diagnosis and antibiotics susceptibility; however, whether treatment failure affects its accuracy remains uninvestigated. Our study aimed to investigate diagnostic accuracy and antibiotics susceptibility of juice PCR in previously treated H pylori and to compare with the current standard of culture. METHODS: We categorized all 547 patients into treatment-naïve, post-1st treatment, post-2nd treatment, and post-3rd treatment. Helicobacter pylori infection was confirmed using gold standards. Sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve and area under ROC curve (AUC) of juice PCR and culture were calculated. Intra-gastric H pylori density was evaluated. Lastly, the antibiotics susceptibility results of gastric juice and culture were compared. RESULTS: Our findings demonstrated AUC was higher in juice PCR than culture in all patients (96.7% vs 91.3%, P < 0.0001). The superiority of juice PCR was statistically significant in previously treated patients (P < 0.0001) but not in treatment-naïve patients (P = 0.13). Antral H pylori density was less marked in previously treated patients (P = 0.014). The comparisons of PCR-RFLP and E-test for Clarithromycin resistance showed reliable AUC = 89.8%. CONCLUSION: Compared with the current standard of culture, the gastric juice PCR contains the strengths of performing the antibiotics susceptibility and overcomes the shortcomings of low accuracy. Consequently, gastric juice PCR suits the unmet need to manage previously treated H pylori.
Assuntos
Suco Gástrico/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carga Bacteriana , Biópsia , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Sensibilidade e Especificidade , Estômago/microbiologia , Falha de TratamentoRESUMO
Fecal microbiota transplantation (FMT) is a method to directly change the recipient's gut microbiota to normalize the composition and gain a therapeutic benefit. The history of FMT has been traced back to the 4th century and has been highly regarded since 2013, when the United States Food and Drug Administration approved FMT for treating recurrent and refractory Clostridium difficile infection. Since then, the range of FMT applications extended rapidly and broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Donor selection with questionnaire, interview, blood tests, and stool examinations should be strictly performed before FMT to reduce and prevent occurrence of any adverse events. Step-by-step cautious fecal and recipient preparation along with adequately choosing delivery methods based on individual clinical situations are key points of the FMT process. Although current evidence deems FMT as a generally safe therapeutic method with few adverse effects, the long-term outcomes of FMT have not been completely elucidated. Therefore, establishing periodicity and length of regular follow-up after FMT to monitor the clinical efficacy and long-term adverse events are other essential issues. In the future, we will look forward to personalized FMT for different patients and conditions according to varied hosts and diseases.
Assuntos
Infecções por Clostridium/terapia , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/métodos , Gastroenteropatias/terapia , Clostridioides difficile , Transplante de Microbiota Fecal/tendências , Humanos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Helicobacter pylori (H. pylori) infection causes elevation of lipid peroxidation product malondialdehyde (MDA) and this association may be due to the bacterium causing reactive oxygen species-mediated damage to DNA in the gastric epithelium. The aim of this study was to investigate the gastric juice MDA levels in relation to H. pylori infection and associated gastric diseases. METHODS: Gastric juice samples were obtained from 117 patients undergoing endoscopy, and gastric juice MDA levels were determined by high-performance liquid chromatography (HPLC) system. We compared the MDA levels between patients with and without H. pylori infection and assessed the differences of MDA levels between chronic gastritis, gastric intestinal metaplasia, and gastric cancer postsurgical resection. RESULTS: Malondialdehyde levels in gastric juice were significantly higher in chronic gastritis patients with H. pylori infection than in those without H. pylori infection (P < .0001). In patients without H. pylori infection, patients with gastric intestinal metaplasia and gastric cancer postsurgical resection had significantly higher gastric juice MDA level than patients with chronic gastritis. As a whole, patients with gastric intestinal metaplasia and gastric cancer postsurgical resection also had significantly higher MDA levels in gastric juice as compared to patients with chronic gastritis (P < .01). However, the difference of gastric juice MDA levels between gastric intestinal metaplasia and gastric cancer postsurgical resection was not significant. CONCLUSION: Malondialdehyde in gastric juice could be used as a potential diagnostic biomarker for H. pylori infection and associated gastric diseases. The gastric juice MDA levels increased proportionally with the severity of gastric diseases.
Assuntos
Suco Gástrico/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/patogenicidade , Malondialdeído/metabolismo , Idoso , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/metabolismo , Gastrite/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologiaRESUMO
Few studies have focused on premenstrual symptoms in employees. This study explored the prevalence of premenstrual symptoms in 7,193 female employees aged 18-55 years in a large electronics manufacturer in Taiwan from August 2014 to December 2014 and examined whether regular exercise was associated with premenstrual symptoms. Information was collected on demographics, lifestyle, menstrual history, menstrual pain, and premenstrual symptoms. Half of the participants reported irregular menstruation; 79.4% reported a moderate menstruation amount, and half reported little impact of menstrual pain at work. In order of prevalence, symptoms were "easy to fatigue" (24%), "backache" (21.2%), and "abdominal bloating" (17.4%). Participants who engaged in regular exercise reported fewer backaches (adjusted odds ratio [aOR] = 0.79, 95% confidence interval [CI] = 0.68-0.91), somatic discomfort (aOR = 0.78, 95% CI = 0.63-0.96), headache (OR = 0.82, 95% CI = 0.69-0.98), diarrhea (aOR = 0.76, 95% CI = 0.60-0.96), constipation (aaOR = 0.59, 95% CI = 0.44-0.78), less irritability (aOR = 0.78, 95% CI = 0.65-0.94), feeling morose and depressed (aOR = 0.75, 95% CI = 0.58-0.95), crying (aOR = 0.51, 95% CI = 0.27-0.87), and emotional lability (aOR = 0.73, 95% CI = 0.58-0.91). Regular exercise was associated with decreased menstrual pain (aOR = 0.85, 95% CI = 0.76-0.96). Our findings provide a better understanding of premenstrual symptoms in female workers, allowing for the development of premenstrual health programs to improve their health and quality of life.
Assuntos
Exercício Físico , Menstruação/psicologia , Síndrome Pré-Menstrual/epidemiologia , Qualidade de Vida , Adolescente , Adulto , Sintomas Afetivos/epidemiologia , Sintomas Afetivos/psicologia , Estudos Transversais , Fadiga/epidemiologia , Fadiga/psicologia , Feminino , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Síndrome Pré-Menstrual/etnologia , Síndrome Pré-Menstrual/psicologia , Prevalência , Autorrelato , Inquéritos e Questionários , Taiwan/epidemiologia , Adulto JovemRESUMO
The management of proton pump inhibitor-refractory GERD (rGERD) is a challenge in clinical practice. Since up to one-third of patients with typical GERD symptoms (heartburn and/or acid regurgitation) are not satisfied with proton pump inhibitor (PPI) therapy, new drug development targeting different pathophysiologies of GERD is imperative. At present, no other drugs serve as a more potent acid suppression agent than PPIs. As an add-on therapy, histamine type-2 receptor antagonists, alginates, prokinetics and transient lower esophageal sphincter relaxation inhibitors have some impact on the subgroups of rGERD, but greater effectiveness and fewer adverse effects for widespread use are required. Visceral hypersensitivity also contributes to the perception of GERD symptoms, and neuromodulators including antidepressants play a role in this category. Esophageal pH-impedance monitoring helps to distinguish functional heartburn from true GERD, and psychologic medication and cognitive behavior therapy are further therapy options instead of PPIs.
Assuntos
Alginatos/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Esfíncter Esofágico Inferior/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Fármacos Gastrointestinais/uso terapêutico , Ácido Glucurônico/uso terapêutico , Ácidos Hexurônicos/uso terapêutico , HumanosRESUMO
Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs-mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin-8 (IL-8) protein. Administration of IL-8 specific neutralizing antibody significantly inhibits HBMMSCs-mediated gastric cancer motility. Treatment of recombinant IL-8 soluble protein confirmed the role of IL-8 in mediating HBMMSCs-up-regulated cell motility. IL-8 up-regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17ß -estradiol inhibit HBMMSCS-induced cell motility via suppressing activation of IL8-Src signalling in human gastric cancer cells. 17ß-estradiol inhibits IL8-up-regulated Src downstream target proteins including p-Cas, p-paxillin, p-ERK1/2, p-JNK1/2, MMP9, tPA and uPA. These results suggest that 17ß-estradiol significantly inhibits HBMMSCS-induced invasive motility through suppressing IL8-Src signalling axis in human gastric cancer cells.
Assuntos
Células Epiteliais/efeitos dos fármacos , Estradiol/farmacologia , Regulação Neoplásica da Expressão Gênica , Interleucina-8/genética , Células-Tronco Mesenquimais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Técnicas de Cocultura , Proteína Substrato Associada a Crk/antagonistas & inibidores , Proteína Substrato Associada a Crk/genética , Proteína Substrato Associada a Crk/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Mucosa Gástrica/metabolismo , Humanos , Interleucina-8/antagonistas & inibidores , Interleucina-8/metabolismo , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Paxilina/antagonistas & inibidores , Paxilina/genética , Paxilina/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/antagonistas & inibidores , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Transdução de Sinais , Estômago/patologiaRESUMO
BACKGROUND: The acid-suppressive agents have been linked with an increased risk of infectious disease. The relationship between these drugs and Mycobacterium Tuberculosis (TB) was not been reported. METHODS: We conducted a case-control study using data from National Health Insurance research database of Taiwan. From 1996 till 2008, and 6541 cases were defined as TB infection/activation (ICD-9 coding plus prescription two of four first-line anti-TB regimen for at least one month). Control subjects who were matched to the TB cases by age and sex were selected with 10:1 ratio. Medical records including acid-suppressive agent prescription and comorbidity, and socioeconomic status were analyzed. RESULTS: TB infection/activation was more frequent to comorbidity with chronic diseases, alcohol abuse, malignancy, immune deficient/suppression status and acid-related disease (peptic ulcer, reflux esophagitis). Among the TB cases, there was higher exposure record to acid-suppressive agents within 3 months before TB index date (OR 2.43(2.06-2.88) and 1.90 (1.68-2.14) for proton pump inhibitor (PPI) and histamine 2 receptor antagonist (H2RA) respectively). After adjusting confounding factors, PPIs prescription 3 months before TB index date had an association of TB infection/activation (adjusted OR 1.63(1.61-1.63)). Similar result was found in H2RA user (adjusted OR 1.51(1.50-1.52)). The association of acid-suppressive agents in TB infection/activation was fade gradually when the drug prescription period extended. CONCLUSIONS: Recent prescription of acid-suppressive agent seems to associate the TB infection/activation. In the society where TB was prevalent, evaluation of pulmonary TB before prescription of PPI or H2RA is warranted.
Assuntos
Antiulcerosos/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Tuberculose/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Fatores de TempoRESUMO
Gender differences in terms of mortality among many solid organ malignancies have been proved by epidemiological data. Estrogen has been suspected to cast a protective effect against cancer because of the lower mortality of gastric cancer in females and the benefits of hormone replacement therapy (HRT) in gastric cancer. Hence, it suggests that 17ß-estradiol (E2) may affect the behavior of cancer cells. One of the key features of cancer-related mortality is metastasis. Accumulating evidences suggest that human bone marrow mesenchymal stem cells (HBMMSCs) and its secreted CCL-5 have a role in enhancing the metastatic potential of breast cancer cells. However, it is not clear whether E2 would affect HBMMSCs-induced mobility in gastric cancer cells. In this report, we show that CCL-5 secreted by HBMMSCs enhanced mobility in human AGS gastric cancer cells via activation of Src/Cas/Paxillin signaling pathway. Treatment with specific neutralizing antibody of CCL-5 significantly inhibited HBMMSCs-enhanced mobility in human AGS gastric cancer cells. We further observe that 17ß-estradiol suppressed HBMMSCs-enhanced mobility by down-regulating CCL5-Src/Cas/paxillin signaling pathway in AGS cells. Collectively, these results suggest that 17ß-estradiol treatment significantly inhibits HBMMSCS-induced mobility in human AGS gastric cancer cells.
Assuntos
Quimiocina CCL5/metabolismo , Estradiol/farmacologia , Células-Tronco Mesenquimais/patologia , Paxilina/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Quinases da Família src/metabolismo , Anticorpos Neutralizantes/farmacologia , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Quimiocina CCL5/genética , Quimiocina CCL5/imunologia , Proteína Substrato Associada a Crk/metabolismo , Regulação para Baixo/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/metabolismo , Quinases da Família src/antagonistas & inibidoresRESUMO
Mitochondria are essential for energy supplementation and metabolic homeostasis of cancer cells. Using mitochondria transplantation to reduce the malignancy of gastric cancer (GC) cells is herein proposed. In our study normal human gastric mucous epithelium cell line (GES-1) showed a lower mitochondrial membrane potential (MMP) compared to immortalized human vascular endothelial cell line (EAhy 926) and human gastric adenocarcinoma cell line (AGS). The transplantation of GES-1 mitochondria to AGS were confirmed both by confocal microscopy and flow cytometry. After transplanting GES-1 mitochondria, the AGS showed a reduced cell migration, and invasion without affecting cell viability and apoptosis. Investigating the expression of proteins involved in epithelial-mesenchymal-transition (EMT), transplanted GES-1 mitochondria reduced the expression of mesenchymal markers α-SMA, MMP-9, snail, vimentin and N-cadherin, whereas the epithelial markers E-cadherin and clauding-1 were not changed. The proteins implicated in the cell cycle such as cyclin B1 and D1 were decreased. In mice, inoculation with AGS carrying the transplanted GES-1 mitochondria resulted in smaller sized tumors. Further investigating the mitochondrial balance, the transplanted GES-1 mitochondria were more stably preserved compared to endogenous AGS mitochondria. The MMP, ATP production and mitochondrial mass decreased in GES-1 mitochondria and the mitophagic proteins LC3 II and PINK1 were up-regulated. In conclusion the decreased malignancy of AGS was a result of exogenous GES-1 mitochondria transplantation. This suggests for a therapy with low efficiency mitochondria transplantation in the treatment of cancer cells.
RESUMO
OBJECTIVES: This prospective study was designed to compare the efficacies of levofloxacin-containing and high-dose metronidazole-containing quadruple therapies after failure of standard triple therapies. METHODS: A total of 150 Helicobacter pylori-infected patients were enrolled in our study and randomly assigned to levofloxacin-containing quadruple therapy (EBTL group) (40 mg of esomeprazole twice daily, 300 mg of bismuth subcitrate four times daily, 500 mg of tetracycline four times daily and 500 mg of levofloxacin once daily for 10 days) (n = 76) or high-dose metronidazole-based quadruple therapy (EBTM group) (40 mg of esomeprazole twice daily, 300 mg of bismuth subcitrate four times daily, 500 mg of tetracycline four times daily and 500 mg of metronidazole four times daily for 10 days) (n = 74). Follow-up endoscopy or urea breath test was done 16 weeks later to assess the treatment response. Patients' responses, CYP2C19 genotypes and antibiotic resistances were also examined. All participants, caregivers and those assessing the outcomes were blinded to group assignment. RESULTS: Intention-to-treat analysis revealed that both groups showed similar eradication rates: EBTL, 78.9% (60/76) (95% CI 69.7%-88.1%) and EBTM, 79.7% (59/74) (95% CI 70.5%-88.7%) [risk ratio (RR) 0.97, 95% CI 0.44-2.14]. Per-protocol results were EBTL = 87.0% (60/69) (95% CI 79.4%-94.9%) and EBTM = 90.8% (59/65) (95% CI 83.8%-97.8%) (RR 0.68, 95% CI 0.23-2.0). We did not find significant differences in compliance (RR 0.5, 95% CI 0.54-2.3) and adverse events (RR 1.11, 95% CI 0.54-2.3) between the two groups. Logistic regression analysis showed that only compliance was an important predictor for eradication failure. CYP2C19 polymorphism did not influence the eradicating effect. CONCLUSIONS: The 10 day bismuth quadruple therapies with high-dose metronidazole or levofloxacin were effective even in areas with high resistance. These two therapies were equally safe and tolerated. Besides this, the metronidazole-containing therapy was cheaper. So it is persuasive that high-dose metronidazole-containing quadruple therapy could be a good choice for second-line H. pylori eradication in areas with high resistance.
Assuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Levofloxacino , Metronidazol/administração & dosagem , Ofloxacino/administração & dosagem , Compostos Organometálicos/administração & dosagem , Adulto , Idoso , Antibacterianos/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Although the association between chronic Helicobacter pylori infection and type 2 diabetes has been suggested, findings have been inconsistent. This study evaluated the association between chronic H. pylori infection and glucose regulation. MATERIALS AND METHODS: We evaluated H. pylori infection status of participants recruited from the gastroenterology clinic at our hospital. At baseline, we performed blood tests including fasting plasma glucose, insulin, glycated haemoglobin A1c (HbA1c) and other biochemical measurements. Insulin resistance and beta-cell function were assessed by homoeostasis model assessment (HOMA-IR and HOMA-B, respectively). RESULTS: A total of 2070 participants were recruited. Those who had H. pylori infections had higher serum HbA1c levels and lower HOMA-B than those who did not (5.78% vs. 5.69%, P = 0.01 and 53.85 + 38.43 vs. 60.64 + 43.40, P = 0.009, respectively). They also had a significantly higher prevalence of type 2 diabetes (8.97% vs. 5.57%, P= 0.02). Chronic H. pylori infection was significantly associated with high levels of HbA1c and type 2 diabetes in participants above 65 years old (P = 0.001) and decreased insulin secretion and sensitivity in those under 45 years (P = 0.05). CONCLUSIONS: Long-term H. pylori infection is significantly associated with high levels of HbA1c and decreased insulin secretion in this Chinese population. Proper screening for H. pylori infection combined with regular monitoring of blood glucose and HbA1c levels might be effective for the early detection of glucose dysregulation and prevention of type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Hemoglobinas Glicadas/metabolismo , Infecções por Helicobacter/complicações , Helicobacter pylori , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Diagnóstico Precoce , Feminino , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Homeostase/fisiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND/PURPOSE: This study aims to establish reference intervals for important biochemical parameters in cord blood of newborn male and female infants in Taiwan and to investigate their sex difference. We also examined the correlation of the same markers between maternal blood levels and neonatal cord blood levels. METHODS: 2,136 pregnant women receiving regular routine prenatal health assessments in their third trimester (weeks 29-40) were recruited from nine hospitals in Taiwan between 2012 and 2015. After exclusion, we were left with 580 cord blood samples to include in this study. RESULTS: Cord blood thyroid-stimulating hormone was higher in males than females (p < 0.05). Males also had significantly higher sex hormone levels (estradiol, follicle-stimulating hormone, and sex hormone-binding globulin), while females had higher levels of luteinizing hormone. Male newborns had higher cord blood immunoglobulin E (IgE), while females had higher insulin-like growth factor-1 (IGF-1) levels. We found a slight positive link between maternal blood and cord blood in thyroid hormones and sex hormones. CONCLUSION: This study found sex differences in cord blood thyroid hormone, sex hormone, IGF-1, and IgE levels and a link between maternal blood levels of thyroid and sex hormones and those in the cord blood of their infants.
Assuntos
Sangue Fetal , Fator de Crescimento Insulin-Like I , Feminino , Gravidez , Masculino , Recém-Nascido , Humanos , Hormônios Tireóideos , Hormônios Esteroides Gonadais , Imunoglobulina ERESUMO
Helicobacter pylori infection is an important issue worldwide, and several guidelines have been published for clinicians to achieve successful eradication. However, there are still some patients who remain infected with H. pylori after treatment. Clinicians should identify the reasons that caused treatment failure and find strategies to manage them. We have searched and organized the literature and developed methods to overcome factors that contribute to prior treatment failure, such as poor compliance, inadequate intragastric acid suppression, and antibiotic resistance. To improve compliance, telemedicine or smartphone applications might play a role in the modern world by increasing doctor-patient relationships, while concomitant probiotics could be administered to reduce adverse effects and enhance adherence. For better acid suppression, high-potency and high-dose proton-pump inhibitors or potassium-competitive acid blockers have preferable efficacy. To overcome antibiotic resistance, susceptibility tests either by culture or by genotyping are the most commonly used methods and have been suggested for antibiotic selection before rescue therapy, but empirical therapy according to detailed medical history could be an alternative. Eradication with a longer treatment period (14 days) has a better outcome than shorter period (7 or 10 days). Ultimately, clinicians should select antibiotics based on the patient's history of drug allergy, previous antibiotic exposure, local antibiotic resistance, available medications, and cost. In addition, identifying patients with a high risk of cancer and shared decision-making are also essential for those who have experienced eradication failure.
RESUMO
Maternal exposure to di-(2-ethylhexyl)-phthalate (DEHP), an environmental endocrine disruptor, may lead to developmental immunotoxicity in offspring. The causal relationship and underlying mechanism require further study. A subset of Taiwan Maternal and Infant Cohort Study data (n = 283) was analyzed and found a significant association between urinary DEHP metabolite levels from the third trimester of pregnancy and plasma levels of IL-28A and IL-29, named IFNλs, in cord blood. A trans-maternal murine model mimicking human DEHP exposure way showed that bone marrow-derived dendritic cells from maternal DEHP-exposed F1 offspring secreted higher IL-28A levels than control cells, indicating a potential causal relationship. Human bronchial epithelial cell lines treated with DEHP or its primary metabolite, mono-(2-ethyl-5-hexyl) phthalate (MEHP), expressed significantly higher levels of IFNλs mRNA or protein than controls. MEHP's effect on IFNλs expression was blocked by peroxisome proliferator-activated receptor α (PPARα) and PPARγ antagonists, and inhibited by a histone acetyltransferase inhibitor or a histone methyltransferase inhibitor. Chromatin immunoprecipitation assay showed that MEHP treatment promoted histone modifications at H3 and H4 proteins at the promoter regions of Il28a and Il29 genes. These results suggest maternal DEHP exposure could result in high IFNλ expression in offspring, and the health risk of early-life exposure requires further investigation.
Assuntos
Dietilexilftalato , Lactente , Feminino , Gravidez , Humanos , Animais , Camundongos , Regulação para Cima , Interferon lambda , Coorte de Nascimento , Estudos de Coortes , Modelos Animais de Doenças , Exposição Materna , CitocinasRESUMO
Background: Few studies assess cord blood biomarkers to predict prenatal exposure to di(2-ethylhexyl) phthalate (DEHP) on the development of allergic diseases later in childhood. IL-33 has been indicated to play an important role in allergic diseases. We evaluated the association of prenatal DEHP exposure and IL-33 in cord blood on the development of allergic diseases. We also investigated the mechanism of DEHP in human lung epithelial cells and asthma animal models. Methods: 66 pregnant women were recruited, and their children followed when they were aged 3 years. Maternal urinary DEHP metabolites were determined using liquid chromatography-electrospray-ionization-tandem mass spectrometry. The effect of DEHP on IL-33 production was investigated in human lung epithelial cells and club cell-specific aryl hydrocarbon receptor (AhR) deficiency mice. ELISA and RT-PCR, respectively, measured the IL-33 cytokine concentration and mRNA expression. Results: The concentrations of maternal urinary DEHP metabolites and serum IL-33 in cord blood with childhood allergy were significantly higher than those in the non-childhood allergy group. DEHP and MEHP could induce IL-33 production and reverse by AhR antagonist and flavonoids in vitro. Enhanced ovalbumin-induced IL-4 and IL-33 production in bronchoalveolar lavage fluid (BALF) by DEHP exposure and suppressed in club cell-specific AhR null mice. Kaempferol has significantly reversed the DEHP effect in the asthma animal model. Conclusions: Cord blood IL-33 level was correlated to childhood allergy and associated with maternal DEHP exposure. IL-33 might be a potential target to assess the development of DEHP-related childhood allergic disease. Flavonoids might be the natural antidotes for DEHP.
Assuntos
Asma , Dietilexilftalato , Hipersensibilidade , Interleucina-33 , Animais , Feminino , Humanos , Camundongos , Gravidez , Asma/induzido quimicamente , Dietilexilftalato/toxicidade , Receptores de Hidrocarboneto Arílico/genética , Pré-Escolar , Exposição MaternaRESUMO
Recent experimental and observational research has suggested that childhood allergic asthma and other conditions may be the result of prenatal exposure to environmental contaminants, such as di-(2-ethylhexyl) phthalate (DEHP). In a previous epidemiological study, we found that ancestral exposure (F0 generation) to endocrine disruptors or the common plasticizer DEHP promoted allergic airway inflammation via transgenerational transmission in mice from generation F1 to F4. In the current study, we employed a MethylationEPIC Beadchip microarray to examine global DNA methylation in the human placenta as a function of maternal exposure to DEHP during pregnancy. Interestingly, global DNA hypomethylation was observed in placental DNA following exposure to DEHP at high concentrations. Bioinformatic analysis confirmed that DNA methylation affected genes related to neurological disorders, such as autism and dementia. These results suggest that maternal exposure to DEHP may predispose offspring to neurological diseases. Given the small sample size in this study, the potential role of DNA methylation as a biomarker to assess the risk of these diseases deserves further investigation.