RESUMO
Ethanolic fermentation is frequently performed under conditions of low nitrogen. In Saccharomyces cerevisiae, nitrogen limitation induces macroautophagy, including the selective removal of mitochondria, also called mitophagy. Previous research showed that blocking mitophagy by deletion of the mitophagy-specific gene ATG32 increased the fermentation performance during the brewing of Ginjo sake. In this study, we tested if a similar strategy could enhance alcoholic fermentation in the context of fuel ethanol production from sugarcane in Brazilian biorefineries. Conditions that mimic the industrial fermentation process indeed induce Atg32-dependent mitophagy in cells of S. cerevisiae PE-2, a strain frequently used in the industry. However, after blocking mitophagy, no significant differences in CO2 production, final ethanol titers, or cell viability were observed after five rounds of ethanol fermentation, cell recycling, and acid treatment, which is commonly performed in sugarcane biorefineries. To test if S. cerevisiae's strain background influenced this outcome, cultivations were carried out in a synthetic medium with strains PE-2, Ethanol Red (industrial), and BY (laboratory) with and without a functional ATG32 gene and under oxic and oxygen restricted conditions. Despite the clear differences in sugar consumption, cell viability, and ethanol titers, among the three strains, we did not observe any significant improvement in fermentation performance related to the blocking of mitophagy. We concluded, with caution, that the results obtained with Ginjo sake yeast were an exception and cannot be extrapolated to other yeast strains and that more research is needed to ascertain the role of autophagic processes during fermentation. IMPORTANCE Bioethanol is the largest (per volume) ever biobased bulk chemical produced globally. The fermentation process is well established, and industries regularly attain nearly 85% of maximum theoretical yields. However, because of the volume of fuel produced, even a small improvement will have huge economic benefits. To this end, besides already implemented process improvements, various free energy conservation strategies have been successfully exploited at least in laboratory strains to increase ethanol yields and decrease byproduct formation. Cellular housekeeping processes have been an almost unexplored territory in strain improvement. It was previously reported that blocking mitophagy by deletion of the mitophagy receptor gene ATG32 in Saccharomyces cerevisiae led to a 2.1% increase in final ethanol titers during Japanese sake fermentation. We found in two commercially used bioethanol strains (PE-2 and Ethanol Red) that ATG32 deficiency does not lead to a significant improvement in cell viability or ethanol levels during fermentation with molasses or in a synthetic complete medium. More research is required to ascertain the role of autophagic processes during fermentation conditions.
Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Bebidas Alcoólicas , Proteínas Relacionadas à Autofagia , Etanol , Fermentação , Microbiologia Industrial , Mitofagia , Receptores Citoplasmáticos e Nucleares , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
BACKGROUND: The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. CASE PRESENTATION: A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. CONCLUSIONS: The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.
Assuntos
Cistostomia , Histerectomia Vaginal/efeitos adversos , Prolapso de Órgão Pélvico/cirurgia , Bexiga Urinária/cirurgia , Incontinência Urinária/etiologia , Idoso , Feminino , Humanos , Pós-Menopausa , Resultado do Tratamento , Bexiga Urinária/diagnóstico por imagem , Cateterismo Urinário , Procedimentos Cirúrgicos Urológicos , Vagina/cirurgiaRESUMO
Glucose levels and type 2 diabetes (T2D) are both associated with tumorigenesis and epithelial-mesenchymal transitions (EMTs). EMTs facilitate bladder cancer (BC) metastasis development, but the mechanism by which high-glucose levels promote these EMTs in BC remains unclear. Therefore, we sought to elucidate the mechanism underlying EMT promotion due to increased glucose levels. T24 and UMUC-3 cells were cultured in media containing different glucose concentrations. YAP1, TAZ, GLUT1 and EMT-associated marker expression was analysed via Western blotting and qPCR. BC cell proliferation and invasion were assessed using MTT and Transwell assays, respectively. A xenograft nude mouse model of diabetes was used to evaluate tumour growth and metastasis in vivo. T2D was positively associated with pathologic grade (P = .016) and TNM stage (P < .001) in BC. High glucose triggered BC cell proliferation and invasion in both in vitro and in vivo conditions. High-glucose levels also promoted EMTs in BC cells and increased YAP1 and TAZ expression. YAP1 or TAZ knockdown altered EMT marker expression and decreased GLUT1 expression. Overall, our results suggest that high-glucose levels promote EMTs in BC cells via YAP1 and TAZ regulation. These effector molecules may be promising therapeutic targets for BC cases comorbid with T2D.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucose/toxicidade , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Meios de Cultura , Feminino , Transportador de Glucose Tipo 1/metabolismo , Humanos , Hiperglicemia/complicações , Masculino , Metformina/farmacologia , Camundongos Nus , Pessoa de Meia-Idade , Modelos Biológicos , Invasividade Neoplásica , Metástase Neoplásica , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Sinalização YAPRESUMO
Growing reports indicate that long noncoding RNA (lncRNA) are involved in the regulation of various biological processes of cancer cells. LINC00319 is an ill investigated lncRNA and has been shown to regulate lung cancer, nasopharyngeal carcinoma and ovarian cancer. Nevertheless, its roles in bladder cancer (BCa) remain unclear. In our research, LINC00319 was shown to be an upregulated lncRNA in BCa tissues. LINC00319 expression is negatively correlated with the patient's prognosis. Silencing of LINC00319 suppressed BCa proliferation and invasiveness. In addition, the data indicated LINC00319 was a sponge for miR-4492 and miR-4492 suppressed ROMO1 expression in BCa. Furthermore, our results illustrated miR-4492/ROMO1 axis regulates proliferation, migration, and invasion and LINC00319 exerts oncogenic roles through modulating miR-4492/ROMO1 axis. In sum, this study suggested that LINC00319 acts as oncogenic roles in BCa progression.
Assuntos
Proteínas de Membrana/genética , MicroRNAs/genética , Proteínas Mitocondriais/genética , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Camundongos , Transdução de Sinais/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
Traumatic brain injury (TBI)-induced coagulopathy is a common and well-recognized risk for poor clinical outcomes, but its pathogenesis remains poorly understood, and treatment options are limited and ineffective. We discuss the recent progress and knowledge gaps in understanding this lethal complication of TBI. We focus on (1) the disruption of the brain-blood barrier to disseminate brain injury systemically by releasing brain-derived molecules into the circulation and (2) TBI-induced hypercoagulable and hyperfibrinolytic states that result in persistent and delayed intracranial hemorrhage and systemic bleeding.
Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Lesões Encefálicas Traumáticas/complicações , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/mortalidade , Testes de Coagulação Sanguínea , Plaquetas/metabolismo , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/metabolismo , Endotélio/metabolismo , Fibrinólise , Humanos , Fenótipo , Avaliação de SintomasRESUMO
Coagulopathy is common in patients with traumatic brain injury (TBI) and predicts poor clinical outcomes. We have shown that brain-derived extracellular microvesicles, including extracellular mitochondria, play a key role in the development of TBI-induced coagulopathy. Here, we further show in mouse models that the apoptotic cell-scavenging factor lactadherin, given at a single dose of 400 µg/kg 30 minutes before (preconditioning) or 30 minutes after cerebral fluid percussion injury, prevented coagulopathy as defined by clotting time, fibrinolysis, intravascular fibrin deposition, and microvascular bleeding of the lungs. Lactadherin also reduced cerebral edema, improved neurological function, and increased survival. It achieved these protective effects by enhancing the clearance of circulating microvesicles through phosphatidylserine-mediated phagocytosis. Together, these results identify the scavenging system for apoptotic cells as a potential therapeutic target to prevent TBI-induced coagulopathy and improve the outcome of TBI.
Assuntos
Antígenos de Superfície/uso terapêutico , Transtornos da Coagulação Sanguínea/prevenção & controle , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/genética , Micropartículas Derivadas de Células/efeitos dos fármacos , Proteínas do Leite/uso terapêutico , Fagocitose/efeitos dos fármacos , Animais , Antígenos de Superfície/genética , Antígenos de Superfície/farmacologia , Transtornos da Coagulação Sanguínea/genética , Transtornos da Coagulação Sanguínea/mortalidade , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/patologia , Micropartículas Derivadas de Células/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Leite/genética , Proteínas do Leite/farmacologia , Fagocitose/genética , Sobrevida , Índices de Gravidade do TraumaRESUMO
von Willebrand factor (VWF) is an adhesive ligand, and its activity is proteolytically regulated by the metalloprotease ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat 13). An elevated level of plasma VWF has been widely considered a marker for endothelial cell activation in trauma and inflammation, but its causal role in these pathological conditions remains poorly defined. Using a fluid percussion injury mouse model, we demonstrated that VWF released during acute traumatic brain injury (TBI) was activated and became microvesicle-bound. The VWF-bound microvesicles promoted vascular leakage and systemic coagulation. Recombinant ADAMTS-13 given either before or after TBI reduced the VWF reactivity with minimal influence on VWF secretion. rADAMTS-13 protected the integrity of endothelial cell barriers and prevented TBI-induced coagulopathy by enhancing VWF cleavage without impairing basal hemostasis. Promoting microvesicle clearance by lactadherin had efficacy similar to that of rADAMTS-13. This study uncovers a novel synergistic action between VWF and cellular microvesicles in TBI-induced vascular leakage and coagulopathy and demonstrates protective effects of rADAMTS-13.
Assuntos
Transtornos da Coagulação Sanguínea/metabolismo , Lesões Encefálicas/metabolismo , Células Endoteliais/metabolismo , Microvasos/metabolismo , Fator de von Willebrand/metabolismo , Animais , Transtornos da Coagulação Sanguínea/genética , Transtornos da Coagulação Sanguínea/patologia , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Modelos Animais de Doenças , Células Endoteliais/patologia , Masculino , Camundongos , Camundongos Knockout , Microvasos/patologia , Fator de von Willebrand/genéticaRESUMO
Coagulopathy often develops soon after acute traumatic brain injury and its cause remains poorly understood. We have shown that injured brains release cellular microvesicles that disrupt the endothelial barrier and induce consumptive coagulopathy. Morphologically intact extracellular mitochondria accounted for 55.2% of these microvesicles, leading to the hypothesis that these extracellular mitochondria are metabolically active and serve as a source of oxidative stress that activates platelets and renders them procoagulant. In testing this hypothesis experimentally, we found that the extracellular mitochondria purified from brain trauma mice and those released from brains subjected to freeze-thaw injury remained metabolically active and produced reactive oxygen species. These extracellular mitochondria bound platelets through the phospholipid-CD36 interaction and induced α-granule secretion, microvesiculation, and procoagulant activity in an oxidant-dependent manner, but failed to induce aggregation. These results define an extracellular mitochondria-induced and redox-dependent intermediate phenotype of platelets that contribute to the pathogenesis of traumatic brain injury-induced coagulopathy and inflammation.
Assuntos
Transtornos da Coagulação Sanguínea , Micropartículas Derivadas de Células , Animais , Plaquetas , Camundongos , Mitocôndrias , Agregação Plaquetária , Espécies Reativas de OxigênioRESUMO
Traumatic brain injury (TBI)-induced coagulopathy has long been recognized as a significant risk for poor outcomes in patients with TBI, but its pathogenesis remains poorly understood. As a result, current treatment options for the condition are limited and ineffective. The lack of information is most significant for the impact of blood transfusions on patients with isolated TBI and in the absence of confounding influences from trauma to the body and limbs and the resultant hemorrhagic shock. Here we discuss recent progress in understanding the pathogenesis of TBI-induced coagulopathy and the current state of blood transfusions for patients with TBI and associated coagulopathy.
Assuntos
Transtornos da Coagulação Sanguínea , Transfusão de Sangue , Lesões Encefálicas Traumáticas , Choque Hemorrágico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/terapia , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/terapia , Humanos , Choque Hemorrágico/sangue , Choque Hemorrágico/complicações , Choque Hemorrágico/terapiaRESUMO
OBJECTIVEThe purpose of this study was to compare total cost and length of stay (LOS) between spine surgery patients enrolled in an enhanced perioperative care (EPOC) pathway and patients receiving traditional perioperative care (TRDC).METHODSAll spine surgery candidates were screened for inclusion in the EPOC pathway. This cohort was compared to a retrospective cohort of patients who received TRDC and a concurrent group of patients who met inclusion criteria but did not receive the EPOC (no pathway care [NOPC] group). Direct and indirect costs as well as hospital and intensive care LOSs were analyzed between the 3 groups.RESULTSTotal costs after pathway implementation decreased by $19,344 in EPOC patients compared to a historical cohort of patients who received TRDC and $5889 in a concurrent cohort of patients who did not receive EPOC (NOPC group). Hospital and intensive care LOS were significantly lower in EPOC patients compared to TRDC and NOPC patients.CONCLUSIONSThe implementation of a multimodal EPOC pathway decreased LOS and cost in major elective spine surgeries.
Assuntos
Procedimentos Cirúrgicos Eletivos/economia , Recuperação Pós-Cirúrgica Melhorada , Procedimentos Neurocirúrgicos/economia , Assistência Perioperatória/economia , Coluna Vertebral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Redução de Custos , Cuidados Críticos/economia , Feminino , Custos Hospitalares , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the therapeutic effect of low-dose tadalafil on BPH-induced lower urinary tract symptoms (LUTS) complicated with ED. METHODS: We randomly assigned 126 patients with BPH-induced LUTS and ED to receive daily administration of tadalafil (5 mg) plus tamsulosin hydrochloride sustained-release capsules (0.2 mg) (treatment group â ï¼»T-â ï¼½, n = 42), tadalafil (5 mg) only (treatment group â ¡ ï¼»T-â ¡ï¼½, n = 42) or placebo (control group, n = 42), all for 12 weeks. Before and after 6 and 12 weeks of medication, and at 4 and 8 weeks after drug withdrawal, we recorded and compared the IPSS sub-item scores in the voiding stage and urinary storage symptoms, total IPSS, IIEF-5 scores, and the frequency of sexual activities among the three groups of patients. RESULTS: As for the IPSS sub-item scores in the voiding stage symptoms, T-â showed statistically significant differences between any two of the five time points (P < 0.05), but not T-â ¡ between the baseline and 6-week medication or 8-week withdrawal (P > 0.05), or between 6-week medication and 8-week withdrawal (P > 0.05), nor did the control group among the five time points (P > 0.05). Statistically significant differences were observed between any two of the three groups at 12 weeks of medication and 4 weeks after drug withdrawal (P < 0.05), but not between the T-â ¡ and control groups at 6 weeks of medication or 8 weeks after withdrawal (P > 0.05). As to the IPSS sub-item scores in the urinary storage symptoms, there were significant differences between any two time points in T-â and T-â ¡ (P < 0.05), but not in the control (P > 0.05), nor between T-â and T-â ¡ at 6 or 12 weeks of medication or at 4 or 8 weeks after drug withdrawal (P > 0.05). With regard to the total IPSS, statistically significant differences were found between any two of the three groups at 6 and 12 weeks of medication and 4 and 8 weeks after drug withdrawal (P < 0.05), but not between 6-week medication and 8-week withdrawal in T-â or T-â ¡ (P > 0.05), nor among the five time points in the control group (P > 0.05). Concerning the IIEF-5 scores, there was no significant difference in the frequency of sexual activities between the three groups ï¼ï¼°>0.05ï¼.There were statistically significant differences between any two of the three groups at 6 weeks of medication and 8 weeks after drug withdrawal (ï¼°<0.05), but not between 6-week medication and 4- or 8-week withdrawal (P > 0.05) or between 4- and 8-week withdrawal (P > 0.05) in T-â , nor between 6-week medication and 8-week withdrawal in T-â ¡ (P > 0.05) or among the five time points in the control (P > 0.05), nor between T-â and T-â ¡ at 12 weeks of medication (P > 0.05) or 4 weeks after drug withdrawal (P > 0.05). CONCLUSIONS: Daily administration of tadalafil at 5 mg can effectively improve the IPSS sub-item scores in the urinary storage symptoms and IIEF-5 scores, with a persistent effect after withdrawal similar to that of its combination with other drugs, and therefore can be recommended for the treatment of BPH-induced LUTS complicated with ED.
Assuntos
Disfunção Erétil/tratamento farmacológico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática , Tadalafila/uso terapêutico , Carbolinas , Método Duplo-Cego , Disfunção Erétil/complicações , Humanos , Sintomas do Trato Urinário Inferior/complicações , Masculino , Inibidores da Fosfodiesterase 5 , Tansulosina/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The objective of this study was to assess the relationship between exposure to methylprednisolone (MP) and improvements in motor function among patients with acute traumatic spinal cord injury (TSCI). MP therapy for patients with TSCI is controversial because of the current conflicting evidence documenting its benefits and risks. METHODS: We conducted a retrospective cohort study from September 2007 to November 2014 of 311 patients with acute TSCI who were enrolled into a model systems database of a regional, level I trauma center. We linked outcomes and covariate data from the model systems database with MP exposure data from the electronic medical record. The primary outcomes were rehabilitation discharge in American Spinal Injury Association (ASIA) motor scores (sum of 10 key muscles bilaterally as per International Standards for Neurological Classification of Spinal Cord Injury, range, 0-100) and Functional Independence Measure (FIM) motor scores (range, 13-91). Secondary outcomes measured infection risk and gastrointestinal (GI) complications among MP recipients. For the primary outcomes, multivariable linear regression was used. RESULTS: There were 160 MP recipients and 151 nonrecipients. Adjusting for age, sex, weight, race, respective baseline motor score, surgical intervention, injury level, ASIA Impairment Scale (AIS) grade, education, and insurance status, there was no association with improvement in discharge ASIA motor function or FIM motor score among MP recipients: -0.34 (95% CI, -2.8, 2.1) and 0.75 (95% CI, -2.8, 4.3), respectively. Adjusting for age, sex, race, weight, injury level, and receipt of surgery, no association with increased risk of infection or GI complications was observed. CONCLUSIONS: This retrospective cohort study involving patients with acute TSCI observed no short-term improvements in motor function among MP recipients compared with nonrecipients. Our findings support current recommendations that MP use in this population should be limited.
Assuntos
Anti-Inflamatórios/uso terapêutico , Bases de Dados Factuais , Metilprednisolona/uso terapêutico , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/tratamento farmacológico , Adulto , Anti-Inflamatórios/farmacologia , Estudos de Coortes , Feminino , Humanos , Modelos Lineares , Masculino , Metilprednisolona/farmacologia , Pessoa de Meia-Idade , Recuperação de Função Fisiológica/efeitos dos fármacos , Estudos Retrospectivos , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
There are contradictory results about the effect of angiotensin-converting enzyme inhibitors (ACEIs) on bone. This study was performed to address the skeletal renin-angiotensin system (RAS) activity and the effects of the ACEI, captopril, on the bone of streptozotocin-induced type 1 diabetic mice. Histochemical assessment on bone paraffin sections was conducted by Safranin O staining and tartrate-resistant acid phosphatase staining. Micro-computed tomography was performed to analyze bone biological parameters. Gene and protein expression were determined by real-time polymerase chain reaction and immunoblotting, respectively. Type 1 diabetic mice displayed osteopenia phenotype and captopril treatment showed no osteoprotective effects in diabetic mice as shown by the reduction of bone mineral density, trabecular thickness and bone volume/total volume. The mRNA expression of ACE and renin receptor, and the protein expression of renin and angiotensin II were markedly up-regulated in the bone of vehicle-treated diabetic mice compared to those of non-diabetic mice, and these molecular changes of skeletal RAS components were effectively inhibited by treatment with captopril. However, treatment with captopril significantly elevated serum tartrate-resistant acid phosphatase 5b levels, reduced the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand expression, increased carbonic anhydrase II mRNA expression and the number of matured osteoclasts and decreased transforming growth factor-ß and osteocalcin mRNA expression in the tibia compared to those of diabetic mice. The present study demonstrated that the use of the ACEI, captopril, has no beneficial effect on the skeletal biological properties of diabetic mice. However, this could be attributed, at least partially, to its suppression of osteogenesis and stimulation of osteoclastogenesis, even though it could effectively inhibit high activity of local RAS in the bone of diabetic mice.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Osso e Ossos/efeitos dos fármacos , Captopril/farmacologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/patologia , Fosfatase Ácida/genética , Fosfatase Ácida/metabolismo , Angiotensina II/genética , Angiotensina II/metabolismo , Animais , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/genética , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos DBA , NF-kappa B/genética , NF-kappa B/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , RNA Mensageiro/genética , Distribuição Aleatória , Renina/genética , Renina/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Estreptozocina , Fosfatase Ácida Resistente a Tartarato , Tíbia/efeitos dos fármacos , Tíbia/metabolismo , Tíbia/patologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
The skeletal reninangiotensin system (RAS) is involved in the progression of osteoporosis and the active peptide within the RAS, angiotensin II (ANG II), has deleterious effects on bones. This study was performed to investigate whether suppression of the rate-limiting step of the RAS cascade by the renin inhibitor aliskiren has a benefit on trabecular bone in osteoporotic mice. A postmenopausal osteoporosis model was induced by bilateral ovariectomy. The ovariectomized (OVX) mice were treated with a low (5 mg/kg) or high (25 mg/kg) dose of aliskiren for 6 weeks. Micro-computed tomography was performed to detect trabecular bone parameters of lumbar vertebra and to obtain 3-dimensional (3D) images. Treatment with aliskiren markedly increased bone volume over total volume (p<0.05), trabecular bone number (p<0.05), connectivity density (p<0.05), and bone mineral density (p<0.05) and reduced trabecular bone separation (p<0.05) compared to vehicle-treated OVX mice. Similarly, the 3D images were consistent with the quantitative data that showed aliskiren could markedly reverse the ovariectomy-induced pathological changes of trabecular bone. Thus, this study indicated that the treatment of estrogen-deficient mice with aliskiren could markedly increase bone mass and improve trabecular bone structure, suggesting its potential application in treating postmenopausal osteoporosis.
Assuntos
Amidas/uso terapêutico , Fumaratos/uso terapêutico , Vértebras Lombares/patologia , Osteoporose/tratamento farmacológico , Ovariectomia/efeitos adversos , Renina/antagonistas & inibidores , Animais , Anti-Hipertensivos/uso terapêutico , Feminino , Vértebras Lombares/efeitos dos fármacos , Camundongos , Osteoporose/etiologia , Sistema Renina-Angiotensina/fisiologia , Microtomografia por Raio-XRESUMO
Determining the evolutionary history of mantle oxygen fugacity (fo2) is crucial, as it controls the fo2 of mantle-derived melts and regulates atmospheric composition through volcanic outgassing. However, the evolution of mantle fo2 remains controversial. Here, we present a comprehensive dataset of plume-derived komatiites, picrites, and ambient mantle-derived (meta)basalts, spanning from ~3.8 Ga to the present, to investigate mantle thermal and redox states evolution. Our results indicate that fo2 of both mantle plume-derived and ambient mantle-derived melts was lower during the Archean compared to the post-Archean period. This increase in the fo2 of mantle-derived melts over time correlates with decreases in mantle potential temperature and melting depth. By normalizing fo2 to a constant reference pressure (potential oxygen fugacity), we show that the fo2 of both the mantle plume and ambient upper mantle has remained constant since the Hadean. These findings suggest that secular mantle cooling reduced melting depth, increasing the fo2 of mantle-derived melts and contributing to atmospheric oxygenation.
RESUMO
SHORT VEGETATIVE PHASE (SVP), a member of the MADS-box transcription factor family, has been reported to regulate bud dormancy in deciduous perennial plants. Previously, three LcSVPs (LcSVP1, LcSVP2 and LcSVP3) were identified from litchi genome, and LcSVP2 was highly expressed in the terminal buds of litchi during growth cessation or dormancy stages and down-regulated during growth stages. In this study, the role of LcSVP2 in governing litchi bud dormancy was examined. LcSVP2 was highly expressed in the shoots, especially in the terminal buds at growth cessation stage, whereas low expression was showed in roots, female flowers and seeds. LcSVP2 was found to be located in the nucleus and have transcription inhibitory activity. Overexpression of LcSVP2 in Arabidopsis thaliana resulted in a later flowering phenotype compared to the wild-type control. Silencing LcSVP2 in growing litchi terminal buds delayed re-entry of dormancy, resulting in significantly lower dormancy rate. The treatment also significantly up-regulated litchi FLOWERING LOCUS T2 (LcFT2). Further study indicates that LcSVP2 interacts with an AP2-type transcription factor, SMALL ORGAN SIZE1 (LcSMOS1). Silencing LcSMOS1 promoted budbreak and delayed bud dormancy. Abscisic acid (200 mg/L), which enforced bud dormancy, induced a short-term increase in the expression of LcSVP2 and LcSMOS1. Our study reveals that LcSVP2 may play a crucial role, likely together with LcSMOS1, in dormancy onset of the terminal bud and may also serve as a flowering repressor in evergreen perennial litchi.
RESUMO
Despite modern antiseptic techniques, surgical site infection (SSI) remains a leading complication of surgery. However, the origins of SSI and the high rates of antimicrobial resistance observed in these infections are poorly understood. Using instrumented spine surgery as a model of clean (class I) skin incision, we prospectively sampled preoperative microbiomes and postoperative SSI isolates in a cohort of 204 patients. Combining multiple forms of genomic analysis, we correlated the identity, anatomic distribution, and antimicrobial resistance profiles of SSI pathogens with those of preoperative strains obtained from the patient skin microbiome. We found that 86% of SSIs, comprising a broad range of bacterial species, originated endogenously from preoperative strains, with no evidence of common source infection among a superset of 1610 patients. Most SSI isolates (59%) were resistant to the prophylactic antibiotic administered during surgery, and their resistance phenotypes correlated with the patient's preoperative resistome (P = 0.0002). These findings indicate the need for SSI prevention strategies tailored to the preoperative microbiome and resistome present in individual patients.
Assuntos
Anti-Infecciosos , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/microbiologia , Antibioticoprofilaxia , Pele , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
ABSTRACT: Coagulopathy after traumatic brain injury (TBI) is common and has been closely associated with poor clinical outcomes for the affected patients. Traumatic brain injury-induced coagulopathy (TBI-IC) is consumptive in nature and evolves rapidly from an injury-induced hypercoagulable state. Traumatic brain injury-induced coagulopathy defined by laboratory tests is significantly more frequent than clinical coagulopathy, which often manifests as secondary, recurrent, or delayed intracranial or intracerebral hemorrhage. This disparity between laboratory and clinical coagulopathies has hindered progress in understanding the pathogenesis of TBI-IC and developing more accurate and predictive tests for this severe TBI complication. In this review, we discuss laboratory tests used in clinical and research studies to define TBI-IC, with specific emphasis on what the tests detect and what they do not. We also offer perspective on developing more accurate and predictive tests for this severe TBI complication.
Assuntos
Transtornos da Coagulação Sanguínea , Lesões Encefálicas Traumáticas , Lesões Encefálicas , Trombofilia , Humanos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/complicações , Lesões Encefálicas/complicações , Trombofilia/complicaçõesRESUMO
BACKGROUND AND IMPORTANCE: Spinal vascular malformations (sVMs) are relatively uncommon, accounting for 5% to 10% of all spinal cord lesions. Spetzler and Kim developed a paradigm to classify sVMs based on a variety of characteristics into 1 of 6 types, including a subcategory for exclusively epidural sVMs. There is a paucity of literature focused on this category, specifically sources describing the clinical manifestation and management of these lesions. CLINICAL PRESENTATION: We report 2 cases of purely epidural spinal arteriovenous fistula, with an emphasis on the radiographic features and combined endovascular and microsurgical treatment. We report 2 patients known to have epidural spinal arteriovenous fistula who underwent both embolization and surgical resection between May 2019 and August 2020 at our institution. Data collected included demographic, clinical, and operative course, including age, sex, medical history, presenting symptoms, and preoperative and postoperative imaging. Both of these patients were managed with a combination of an endovascular approach for embolization of feeding arterial source and surgical exploration/resection. In both cases, no residual vascular malformation was identified, and the patients went on to be symptom free after 6 weeks. CONCLUSION: This report describes the use of a combination of endovascular and surgical approaches to achieve maximal benefit for 2 patients. These cases reinforce the value of a staged multimodal treatment approach in achieving good functional outcomes for patients with these rare and challenging entities.
Assuntos
Fístula Arteriovenosa , Malformações Arteriovenosas , Embolização Terapêutica , Humanos , Resultado do Tratamento , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/cirurgia , Embolização Terapêutica/métodos , Fístula Arteriovenosa/cirurgia , Microcirurgia/métodosRESUMO
This study explores the relationship between the storage quality and bacterial microflora in the mushroom Lyophyllum decastes. The surface bacteria of L. decastes were separated by combining the traditional culture plate separation and 16S rRNA sequencing method, to study the effects of ultrasonic (US) treatment on the surface bacteria of L. decastes during storage. The results demonstrated that Pantoea agglomerans and Pseudomonas fluorescens were among the 15 culturable bacteria isolated with traditional plate method during storage, belonging to 2 phyla and 7 genera. US treatment could inhibit the growth and significantly increase cell membrane permeability, and contents extravasation in P. agglomerans, though its inhibitory effect on P. fluorescens was less. The 16S rRNA sequencing revealed, bacteria from 9 phyla and 35 genera were isolated, and P. fluorescens was the dominant species throughout the storage time. These results indicated that the composition of mushroom surface microflora of Control (CK) and US groups are similar, and the bacterial microflora networks analysis also showed a positive correlation. The KEGG annotation for the functional classification of the bacteria showed that a total of 328 pathways were acquired at the KEGG l3 level, and the relative abundance of membrane transport, amino acid metabolism, carbohydrate metabolism, and energy metabolism pathway was high. Moreover, the relative abundance of the surface bacteria of L. decastes also decreased. Hence, the US treatment had a better bacteriostatic effect, maintained the whiteness index and firmness, and improved the sensory quality of L. decastes during storage.