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This study presents a methodology for obtaining a precise impression of the crown margin of prepared teeth by utilizing a two-step impression technique. The method begins with the fabrication of a custom tray made from heat-cured acrylic resin, followed by the acquisition of an initial impression using putty elastomeric material. Subsequently, the impression is relieved around the prepared teeth, and vent holes are strategically placed through both the impression and the tray. Finally, a light-body consistency impression material is applied. This streamlined technique enhances efficiency and minimizes the errors commonly encountered with traditional two-step impression methods.
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STATEMENT OF PROBLEM: Data on the role of artificial intelligence (AI) in dental implant planning is insufficient. PURPOSE: The purpose of this systematic review with meta-analysis was to analyze and evaluate articles that assess the effectiveness of AI algorithms in dental implant planning, specifically in detecting edentulous areas and evaluating bone dimensions. MATERIAL AND METHODS: A systematic review was conducted across the MEDLINE/PubMed, Web of Science, Cochrane, and Scopus databases. In addition, a manual search was performed. The inclusion criteria consisted of peer-reviewed studies that examined the accuracy of AI-based diagnostic tools on dental radiographs for dental implant planning. The most recent search was conducted in January 2024. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the quality of the included articles. RESULTS: Twelve articles met the inclusion criteria for this review and focused on the application of AI in dental implant planning using cone beam computed tomography (CBCT) images. The pooled data indicated an overall accuracy of 96% (95% CI=94% to 98%) for the mandible and 83% (95% CI=82% to 84%) for the maxilla in identifying edentulous areas for implant planning. Eight studies had a low risk of bias, 2 studies had some concern of bias, and 2 studies had a high risk of bias. CONCLUSIONS: AI models have the potential to identify edentulous areas and provide measurements of bone as part of dental implant planning using CBCT images. However, additional well-conducted research is needed to enhance the accuracy, generalizability, and applicability of AI-based approaches.
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OBJECTIVES: To evaluate the peri-implant marginal bone loss (MBL) and prosthodontic complications of maxillary screw-retained implant prosthesis fabricated from digital versus conventional full- arch implant impression. MATERIAL AND METHODS: 28 participants with edentulous maxillary arches were randomly selected and enrolled in two equal groups; Group I conventional impression group (CIG) and Group II Digital impression group (DIG). All patients were rehabilitated with maxillary screwretained implant prosthesis retained by 6 implants. Peri-implant MBL and prosthodontic complications and were registered at 6, 12, and 24 months (m). Data was collected and statistically analyzed. RESULTS: Regarding the effect of time, there was a statistically significant increase in MBL at 6, 12 and 24 m follow-up periods (P<.001). As for the effect of groups, there was no statistically significant difference in MBL between CIG and DIG at 6, 12 and 24 m where P value was 0.083, 0.087 and 0.133 respectively. Prosthetic complications were recorded 19 times in the conventional group and 12 times in the digital group with no significant difference between both groups (P=.303). CONCLUSION: Digital full -arch implant impression is a reliable impression technique and may represent an alternative to conventional impression technique in the fabrication of maxillary screw-retained implant prosthesis.
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BACKGROUND: The efficacy of chemotherapy continues to be limited due to associated toxicity and chemoresistance. Thus, synthesizing and investigating novel agents for cancer treatment that could potentially eliminate such limitations is imperative. OBJECTIVE: The current study aims to explore the anticancer potency of cryptolepine (CPE) analog on Ehrlich ascites carcinoma cells (EACs) in mice. METHODS: The effect of a CPE analog on EAC cell viability and ascites volume, as well as malonaldehyde, total antioxidant capacity, and catalase, were estimated. The concentration of caspase-8 and mTOR in EACs was also measured, and the expression levels of PTEN and Akt were determined. RESULTS: Results revealed that CPE analog exerts a cytotoxic effect on EAC cell viability and reduces the ascites volume. Moreover, this analog induces oxidative stress in EACs by increasing the level of malonaldehyde and decreasing the level of total antioxidant capacity and catalase activity. It also induces apoptosis by elevating the concentration of caspase-8 in EACs. Furthermore, it decreases the concentration of mTOR in EACs. Moreover, it upregulates the expression of PTEN and downregulates the expression of Akt in EACs. CONCLUSION: Our findings showed the anticancer activity of CPE analog against EACs in mice mediated by regulation of the PTEN/Akt/mTOR signaling pathway.
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Antineoplásicos , Carcinoma de Ehrlich , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Estresse Oxidativo , PTEN Fosfo-Hidrolase , Proteínas Proto-Oncogênicas c-akt , Quinolinas , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , PTEN Fosfo-Hidrolase/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Carcinoma de Ehrlich/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quinolinas/farmacologia , Quinolinas/química , Quinolinas/síntese química , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Estrutura Molecular , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Alcaloides IndólicosRESUMO
OBJECTIVES: Mandibular single-implant overdenture is a well-established treatment modality for the management of completely edentulous patients. The use of CAD/CAM printing technology to fabricate complete dentures and overdentures is burgeoning. The trial aimed to clinically evaluate 3D-printed single-implant overdentures and compare outcomes to those of overdentures manufactured using conventional techniques. MATERIALS AND METHODS: A randomized clinical trial (RCT) was designed. Twenty-eight participants were randomly allocated into two equal groups. Participants in the control group received conventionally manufactured single-implant overdentures, while participants in the printed group received digital light processing (DLP) printed single-implant overdentures. An evaluation was conducted to assess the rates of implant survival and success, as well as overdenture survival and success, along with the measurement of maximum biting force (MBF) over a one-year follow-up period. Data was collected and subjected to statistical analysis. Statistical significance was determined using a two-sided p-value with a threshold of less than 0.05. RESULTS: The printed denture group had higher implant survival (100%) and success rates (92.8%) compared to the conventional denture group (85.7% survival, 85.7% success). Overdenture survival and success rates were 100% in the printed group and 78.6% in the conventional group. Both groups showed a significant increase in maximum biting force (MBF) at 3, 6, and 12 months of follow-up (P<0.001). The printed group demonstrated a statistically significant improvement in MBF compared to the conventional group (P<0.001). CONCLUSIONS: 3D-printed mandibular single-implant overdentures may represent an alternative to conventionally fabricated ones.
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STATEMENT OF PROBLEM: The evidence regarding the application of artificial intelligence (AI) in identifying dental implant systems is currently inconclusive. The available studies present varying results and methodologies, making it difficult to draw definitive conclusions. PURPOSE: The purpose of this systematic review with meta-analysis was to comprehensively analyze and evaluate articles that investigate the application of AI in identifying and classifying dental implant systems. MATERIAL AND METHODS: An electronic systematic review was conducted across 3 databases: MEDLINE/PubMed, Cochrane, and Scopus. Additionally, a manual search was performed. The inclusion criteria consisted of peer-reviewed studies investigating the accuracy of AI-based diagnostic tools on dental radiographs for identifying and classifying dental implant systems and comparing the results with those obtained by expert judges using manual techniques-the search strategy encompassed articles published until September 2023. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the quality of included articles. RESULTS: Twenty-two eligible articles were included in this review. These articles described the use of AI in detecting dental implants through conventional radiographs. The pooled data showed that dental implant identification had an overall accuracy of 92.56% (range 90.49% to 94.63%). Eleven studies showed a low risk of bias, 6 demonstrated some concern risk, and 5 showed a high risk of bias. CONCLUSIONS: AI models using panoramic and periapical radiographs can accurately identify and categorize dental implant systems. However, additional well-conducted research is recommended to identify the most common implant systems.
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An artificial replacement for a lost limb or portion of a limb, known as a prosthesis, is a tool that can assist a person to regain their independence. The aim of this project was to evaluate the effect of a self-care program for adults with lower limb prostheses. We used a quasi-experimental research design. We conducted our study at the Physical Medicine and Rehabilitation and Rheumatology Center affiliated with the Armed Forces, located in the Al-Geza Governorate of Egypt using a purposeful sample of 81 adults with lower limb prostheses. We used two tools for data collection: a structured interviewing questionnaire and the Trinity Amputation and Prosthesis Experience Scales (TAPES). The mean age of adults with lower limb prosthesis in our study was 38.91 years (10.53). A total of 64.2% of the study participants (n = 51) were men. We found that before the self-care program, 22.2% of the participants (n = 18) had a satisfactory level of knowledge about self-care, which increased to 88.9% (n = 72) after the program. Before the self-care program, the number of participants with adequate practice levels was 13.6% (n = 11), which increased to 100.0% (n = 81) after the program. We concluded that implementing the self-care program provided a significant improvement in the attendee's total satisfactory knowledge (χ2[79,81] = 72.90, p < .000) and adequate practice levels (p < .001).
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Membros Artificiais , Implantação de Prótese , Autocuidado , Adulto , Feminino , Humanos , Masculino , Amputação Cirúrgica , Implantação de Prótese/reabilitação , Inquéritos e Questionários , Avaliação de Programas e Projetos de Saúde , Pessoa de Meia-Idade , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
BACKGROUND: Genetic instability leads to genome mutations, changes in nucleotide sequences, rearrangements, and gains or losses of part of the chromosomes. This instability can initiate and develop cancer. This study evaluated genomic stability in methotrexate and anthocyanin-treated mammary adenocarcinoma model. Seventy albino mice were divided into seven groups: negative control, anthocyanin, methotrexate, Ehrlich's solid tumor; Ehrlich's solid tumor and methotrexate; Ehrlich's solid tumor and anthocyanin; and Ehrlich's solid tumor, methotrexate, and anthocyanin groups. RESULTS: Tumor weight and size were evaluated. Serum arylesterase activity was low in all the induced tumors and those treated with anthocyanin, methotrexate, or both. Poly[adenosine diphosphate (ADP)-ribose] polymerase activity was high, and glutathione S-transferase activity was low in the tumors treated with anthocyanin, methotrexate, or both, compared with that of the untreated tumor. There was an increase in DNA damage in the mice with solid tumors and those injected with methotrexate or methotrexate and anthocyanin, compared with that in the untreated mice. CONCLUSIONS: There was a decrease in genetic instability and DNA damage in the tumor-bearing mice treated with anthocyanin, with a concomitant increase in nuclear poly[adenosine diphosphate (ADP)-ribose] polymerase activity, compared with those of the untreated group. Anthocyanin exerted positive effects in the treatment of mammary adenocarcinoma.
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AIM: To compare the clinical outcomes of conventional and digital implant impressions in all-on-4 mandibular implant prostheses. MATERIALS AND METHODS: Fifty-six participants were randomly stratified into two control groups (Axial Conventional Impression Group [ACIG] and Tilted Conventional Impression Group [TCIG]), and two test groups (Axial Digital Impression Group [ADIG] and Tilted Digital Impression Group [TDIG]). Conventional pick-up and digital impressions were made for each group, respectively. Participants in ACIG and ADIG received four axial implants, and those in TCIG and TDIG received two anterior axial and two distal tilted implants. All participants received all-on-4 mandibular prostheses and maxillary complete dentures. Implant survival, prosthetic complications, and marginal bone loss were recorded at 6, 12, and 24 months. Data were statistically described in terms of mean ± standard deviation. RESULTS: After 24 months, the implant survival rate was 100%. A significant difference in bone loss was shown between ACIG and ADIG at 6, 12, and 24 months, with P = 0.647, 0.821, and 0.505, respectively. An insignificant difference in bone loss was shown between TCIG and TDIG at 6 ,12, and 24 months, with P = 0.671, 0.935, and 0.687, respectively. No significant difference was shown in prosthodontic complications between all groups throughout the follow-up period. CONCLUSIONS: The digital impressions showed clinically better implant survival, stable peri-implant marginal bone level, and reasonable prosthodontic complications. The present study represents a steppingstone and proof of concept that supports the routine clinical use of digital impressions, especially in a post-COVID-19 world.
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COVID-19 , Implantes Dentários , Prótese Total , Humanos , Maxila/cirurgia , ProstodontiaRESUMO
AIM: To evaluate the oral health-related quality of life (OHRQoL) of patients rehabilitated with conventional or 3D-printed implant overdentures. MATERIALS AND METHODS: A randomized clinical trial (RCT) was designed. Twenty-eight completely edentulous participants were randomly allocated into two equal groups. All participants received two implants with ball attachments. Participants in the control group were rehabilitated with conventionally manufactured polymethyl methacrylate (PMMA) maxillary complete dentures (CDs) and mandibular implant overdentures, while those in the intervention group received digital light processing (DLP)-printed photopolymerizable PMMA maxillary CDs (NextDent) and mandibular implant overdentures. Follow-up appointments were scheduled at 3, 6, and 12 months where Oral Health Impact Profile 19 (OHIPEDENT19) data were used to assess the OHRQoL of the participants. Denture retention was measured using a digital force gauge device. RESULTS: The OHRQoL values were significantly higher (less improvement) in the conventional overdenture group at 6 months (P = 0.02) and 12 months (P = 0.04). A statistically significant difference was found between the mean retention values of the conventional and 3D-printed overdenture groups. For all the follow-up periods, the mean retention values were higher for the 3D-printed overdenture group (P = 0.001). CONCLUSION: 3D-printed overdentures may represent an alternative to conventionally fabricated ones. This study represents a stepping stone and proof of concept that support the potential future use of 3D-printed dentures.
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Implantes Dentários , Revestimento de Dentadura , Prótese Dentária Fixada por Implante , Retenção de Dentadura , Humanos , Mandíbula , Saúde Bucal , Satisfação do Paciente , Impressão Tridimensional , TecnologiaRESUMO
BACKGROUND: Obesity is associated with increased oncological risk and outcomes but the evidence surrounding the effect of body mass index (BMI) on increased risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is still questionable. The purpose of this retrospective study of a large cohort of adult patients transplanted for HCC was to investigate the effect of BMI on the incidence of HCC recurrence and outcome. METHODS: Data from 427 adult recipients transplanted for HCC between 2000 and 2017 were collected. Patients were classified at time of LT according to the World Health Organization BMI classification into 3 groups; group 1: BMI <25 (n=166), group 2: BMI 25-29.9 (n=150) and group 3: BMI ≥30 (n=111). RESULTS: There were no significant changes of mean BMI overtime 26.8±5.0 kg/m2 at time of LT and 28.8±23.1 at 5 years. The recurrence rates of HCC after LT in the three groups were 19%, 16% and 17% respectively. The 5, 10 and 15-year recurrence free survival (RFS) rates were respectively 68.6%, 47.3% and 40.8% in group 1, 73.3%, 66.2% and 49.5% in group 2 and 68.8%, 57.5% and 47.7% in group 3 (log rank P=0.47). CONCLUSIONS: Recipient BMI at time of transplant and during follow-up didn't impact the incidence of HCC recurrence nor long-term patient survival, irrespective to the status of the patients and their tumor characteristic at time of LT. The present study clearly confirms that obesity should not be considered, when selecting patients with HCC to LT, as a predictive factor of recurrence.
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BACKGROUND: Occlusal appliances can distribute aggressive loads which are generated by bruxism and can reduce their frequency. The facebow record, when used in the construction of occlusal appliances, helps in minimizing occlusal discrepancies. This study aimed to compare the effect of CAD/CAM stabilization occlusal splint made with and without facebow for management of bruxer patients. METHOD: 24 Patients who were diagnosed as bruxers were randomly assigned into two equal groups and obtained maxillary CAD/CAM occlusal stabilizing splint recorded with centric relation either with or without using a facebow. The patient satisfaction using the visual analog scale (VAS) was recorded at baseline, one month and three months' follow-up periods. The adjustment time of both splints, from the start of splint delivery until becoming well-fitted and occlusally adjusted, was calculated using a stopwatch. RESULTS: The CAD/CAM occlusal splints with or without the use of facebow improved the patient's satisfaction with no statistically significant difference between both groups at baseline, one month and three months with p values of 0.73, 0.24 and 0.45 respectively. The comparison between the two modalities regarding the adjustment time showed no statistically significant difference between both groups (P = 0.06). CONCLUSION: According to the results of this study; no difference was detected in patient satisfaction and the time required for adjustment of CAD/CAM occlus.
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Clinically, the use of doxorubicin (DOX) is limited due to DOX-induced cardiotoxicity (DIC). The current study aimed to evaluate the cardioprotective effect of trehalose (TRE) against DIC in a female Swiss albino mouse model. Mice were divided into five experimental groups: Gp. I: saline control group (200 µl/mouse saline three times per week for 3 weeks day after day), Gp. II: DOX-treated group (2 mg/kg body weight three times per week for 3 weeks day after day), Gp. III: TRE group (200 µg/mouse three times per week for 3 weeks day after day), Gp. IV: DOX + TRE cotreatment group (animals were coadministered with DOX and TRE as in Gp. II and III, respectively), and Gp. V: DOX + TRE posttreatment group (animals were treated with DOX as in Gp. II followed by treatment with TRE as in Gp. III). DOX-treated mice showed significant elevation in cardiac injury biomarkers (lactate dehydrogenase, creatine kinase isoenzyme-MB, and cardiac troponin I), cardiac oxidative stress (OS) markers (malondialdehyde and myeloperoxidase), and cardiac levels of autophagy-related protein 5. Moreover, DOX significantly reduced the levels of total antioxidant capacity and activities of catalase and glutathione S-transferase. In contrast, TRE treatment of DOX-administered mice significantly improved almost all of the above-mentioned assessed parameters. Furthermore, histopathological changes of cardiac tissues observed in mice treated with TRE in combination with DOX were significantly improved as compared to DOX-treated animals. Taken together, the present study provides evidence that TRE has cardioprotective effects against DIC, which is likely mediated via suppression of OS and autophagy.
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Autofagia/efeitos dos fármacos , Cardiotônicos/farmacologia , Cardiotoxicidade/tratamento farmacológico , Doxorrubicina/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Trealose/farmacologia , Animais , Biomarcadores/metabolismo , Cardiotoxicidade/metabolismo , Doxorrubicina/farmacologia , Feminino , Camundongos , Miocárdio/metabolismoRESUMO
The current study aims to evaluate the modulatory effect of zinc oxide nanoparticles (ZnO NPs) on the bioenergetic signature biomarkers in the Ehrlich ascitic carcinoma (EAC) model. To achieve this goal, 90 female albino mice were included in this study and were divided into six equal groups (n =15 per group): saline-treated group, ZnO NP-treated, EACs-bearing mice, and three groups of EACs-bearing mice treated with ZnO NPs at a dose of 20 mg/kg every other day, 10 mg/kg every other day, 10 mg/kg every day, respectively, for 14 days. The tissues from treated groups and control groups were homogenized and used for the assay of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and F1 beta subunit of adenosine triphosphate (ATP) synthase levels, as well as the determination of lactate level. The survival time of mice was improved in all ZnO NP-treated groups, especially in EACs-bearing mice treated with ZnO NPs at a dose of 10 mg/kg every other day. This improvement was associated with an increased F1 beta subunit of ATP synthase level and a decreased GAPDH level. Also, the lactate level was significantly decreased in all treated groups when compared with the untreated group. The overall effect was the increased bioenergetic signature as compared with EC.These results implied that ZnO NPs have a significant efficacy against cancer cells and they significantly increased the bioenergetic signature.
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Carcinoma de Ehrlich/patologia , Metabolismo Energético , Nanopartículas Metálicas/química , Óxido de Zinco/química , Animais , Biomarcadores/metabolismo , Relação Dose-Resposta a Droga , Feminino , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Ácido Láctico/sangue , Nanopartículas Metálicas/administração & dosagem , Camundongos , ATPases Translocadoras de Prótons/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The anticancer effect of sulforaphane (SFN) is mediated by several signalling pathways. However, little is known regarding the underlying mechanism in Ehrlich solid tumours (ESTs) in mice. This study was conducted to determine molecular changes associated with the anticancer effect of SFN and to compare its preventive (cotreatment) and therapeutic (posttreatment) effects. Ehrlich (murine mammary adenocarcinoma) solid tumour was selected and changes in the gene expression were determined in tumour tissues by the real-time polymerase chain reaction. The results showed that SFN increased the expression of the oxidative stress gene NrF2 and its downstream targets (HO1 and CAT). Conversely, SFN administration decreased the expression of the epigenesis-related genes (HDAC1 and DNMT1) and inflammation-related genes (TNFa, NFkB and Cox2). Overall, SFN cotreatment presented notable molecular changes than the posttreatment strategy. These data suggest that molecular changes associated with the anticancer effects of SFN against EST involved induction of oxidative stress, inhibition of inflammation and epigenetic modifications.
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Anticarcinógenos/uso terapêutico , Carcinoma de Ehrlich/tratamento farmacológico , Isotiocianatos/uso terapêutico , Sulfóxidos/uso terapêutico , Animais , Anticarcinógenos/farmacologia , Carcinoma de Ehrlich/genética , Epigênese Genética/efeitos dos fármacos , Feminino , Inflamação/genética , Inflamação/prevenção & controle , Isotiocianatos/farmacologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Sulfóxidos/farmacologiaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is currently the first indication of liver transplantation (LT) in Europe and Asia-Pacific region and the third in the United States. HCC recurrence is the main complication affecting short- and medium-term outcomes after LT. METHODS: A total of 433 consecutive adult recipients transplanted for HCC between 2000 and 2017 (mean age: 57.8 ± 8.5 y; 83.8% were males) with a mean follow-up of 74.6 ± 58.6 months were included. Patients had to meet Milan criteria and, since 2014, alpha-fetoprotein score to be listed. Patients with HCC recurrence were classified into early (≤2 y) and late recurrence (>2 y) and were retrospectively reviewed. RESULTS: Patients who developed recurrence (75 patients, 17%) had more tumors outside Milan and University of California San Francisco criteria, high alpha-fetoprotein score, and microvascular invasion at pathology. Early recurrence developed in 46 patients (61.3%); the overall 5- and 10-year survival rates of these patients from time of LT were 6.7% and 0%, which were significantly lower than those with late recurrence 64.0% and 27.1%, respectively (P < 0.001). The median survival times from the diagnosis of HCC recurrence were 15 and 17 months, respectively, in the 2 groups (P < 0.001). Multivariable Cox regression analysis identified alcoholic cirrhosis as etiology of the underlying liver disease (hazard ratio [HR] = 3.074; P = 0.007), bilobar tumor at time of LT (HR = 2.001; P = 0.037), and a tumor size (>50 mm) in the explant (HR = 1.277; P = 0.045) as independent predictors of early recurrence. CONCLUSIONS: Improving the prediction of early HCC recurrence could optimize patient selection for LT, potential adjuvant therapy with new targeted drugs and hence, improve long-term survival.
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Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Recidiva Local de Neoplasia/etiologia , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
Neurodegenerative diseases are a common cause of morbidity and mortality worldwide, with oxidative stress, inflammation, and protein aggregation representing the main underlying mechanisms that ultimately lead to cell death. Ethanol has shown strong neurodegenerative consequences in experimental animal brains. Statins are a class of lipid-lowering drugs with many pleotropic effects. Therefore, the aim of the present study was to explore the modulatory effect of simvastatin (10 mg·kg-1·day-1) before and after the development of neurodegeneration (for 55 and 25 days, respectively) on redox state, caspase-3 expression, p-protein kinase B (p-Akt), and brain-derived neurotrophic factor (BDNF) in ethanol-induced (15% ethanol solution for 55 days) neurodegeneration. Seventy female Albino Swiss mice were included and randomly divided into five groups: C, control group; E, ethanol group; ES, group treated with simvastatin from the first day of ethanol intake; E + S, group treated with simvastatin after neurodegeneration development; and S, simvastatin group. Administration of simvastatin from the first day improved the biochemical changes, suppressed apoptosis, and induced autophagy and neurogenesis; however, its administration after the development of neurodegeneration resulted in partial improvement. The histopathological findings confirmed the biochemical changes. In conclusion, simvastatin has a neuroprotective effect against the development of ethanol-induced neurodegeneration and its progression.
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Fator Neurotrófico Derivado do Encéfalo , Animais , Camundongos , Proteínas Proto-Oncogênicas c-akt , SinvastatinaRESUMO
Cancer cells have extra biosynthetic demands to sustain cell growth and redox homeostasis. Glycolysis and autophagy are crucial to fuel and recycle these biosynthetic demands. This plasticity of cancer cell metabolism participates in therapy resistances. The current study was designed to assess the therapeutic efficacy of dual targeting of glycolysis and autophagy in cancer. Using 3-bromopyruvate (3-BP; antiglycolytic inhibitor) and hydroxychloroquine (HCQ; autophagy inhibitor), we demonstrate their antitumor activity in Ehrlich ascites carcinoma (EAC)-bearing mice. A combination of 3-BP and HCQ significantly decreases tumor ascitic volume and cell count as compared with the EAC group and individual treatment groups. The enhanced antitumor activity is accompanied by hexokinase inactivation, inhibition of cellular protective autophagy, elevated antioxidant activity, and reduced oxidative stress levels. Together, these results suggest targeting both pathways in cancer as an effective therapeutic strategy. Further studies are required to validate this strategy in different cancer models and preclinical trials.
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Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Carcinoma de Ehrlich/tratamento farmacológico , Glicólise/efeitos dos fármacos , Hidroxicloroquina/farmacologia , Piruvatos/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Hexoquinase/antagonistas & inibidores , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/metabolismo , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacosRESUMO
Hexokinase-2 is overexpressed in several carcinomas including breast cancer to sustain energy for rapidly dividing cells and associates with chemoresistance. However, the impact of chemo drugs (alone or in combination) on hexokinase activity and autophagic cell death is unclear. In this report, we used an in vivo murine adenocarcinoma model to validate the effects of As2 O3 and cisplatin on hexokinase activity and autophagic cancer cell death. We found that the two drugs inhibit hexokinase activity and induce autophagic marker, beclin 1 expression. Interestingly, combining As2 O3 with cisplatin synergistically enhanced these effects and alleviated oxidative stress often encountered in As2 O3 treatment. Altogether, our data provide direct evidence that inhibition of hexokinase activity and induction of autophagic cell death are mediating the antineoplastic effects of As2 O3 and cisplatin. Our findings raise the potential of combining As2 O3 with cisplatin as an approach to augment cisplatin-induced cell death and combat cisplatin chemoresistance in cancer.
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Antineoplásicos/toxicidade , Trióxido de Arsênio/toxicidade , Carcinoma de Ehrlich/patologia , Cisplatino/toxicidade , Hexoquinase/antagonistas & inibidores , Animais , Antineoplásicos/administração & dosagem , Trióxido de Arsênio/administração & dosagem , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Sinergismo Farmacológico , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacosRESUMO
STATEMENT OF PROBLEM: Osteoporosis is a risk factor for implant success. Evidence for the prognosis of dental implants in patients with osteoporosis is still unclear. PURPOSE: The purpose of this systematic review was to compare implant success in patients with low versus normal bone density and to evaluate special techniques used to enhance implant success in these patients. MATERIAL AND METHODS: Searches were performed electronically in 4 databases (PubMed, LILACS, Cochrane, and Grey Literature) through July 2017 and manually to identify studies addressing the subject. Randomized and nonrandomized clinical trials and cohort studies were included. RESULTS: Eleven studies met the eligibility criteria, with a total of 1071 participants. Seven studies compared implant success in low and normal bone density, and 4 compared implant success in special and conventional techniques of implant placement. The risk of bias in the assessment of cohort studies was critical; of nonrandomized clinical trials, serious; and of randomized clinical trials, high. The meta-analysis showed no significant difference between implant survival in patients with low and normal bone density 5 years after implant placement. CONCLUSIONS: Implant survival in patients with low bone density seems to be feasible with special precautions. Implant placement using special adopted techniques might provide equivalent implant stability, survival, and marginal bone loss to normal bone. The quality of evidence is still unclear.