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1.
Sci Rep ; 14(1): 6530, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503765

RESUMO

Nanoparticulate systems have the prospect of accounting for a new making of drug delivery systems. Nanotechnology is manifested to traverse the hurdle of both physical and biological sciences by implementing nanostructures indistinct fields of science, particularly in nano-based drug delivery. The low delivery efficiency of nanoparticles is a critical obstacle in the field of tumor diagnosis. Several nano-based drug delivery studies are focused on for tumor diagnosis. But, the nano-based drug delivery efficiency was not increased for tumor diagnosis. This work proposes a method called point biserial correlation symbiotic organism search nanoengineering-based drug delivery (PBC-SOSN). The objective and aim of the PBC-SOSN method is to achieve higher drug delivery efficiency and lesser drug delivery time for tumor diagnosis. The contribution of the PBC-SOSN is to optimized nanonengineering-based drug delivery with higher r drug delivery detection rate and smaller drug delivery error detection rate. Initially, raw data acquired from the nano-tumor dataset, and nano-drugs for glioblastoma dataset, overhead improved preprocessed samples are evolved using nano variational model decomposition-based preprocessing. After that, the preprocessed samples as input are subjected to variance analysis and point biserial correlation-based feature selection model. Finally, the preprocessed samples and features selected are subjected to symbiotic organism search nanoengineering (SOSN) to corroborate the objective. Based on these findings, point biserial correlation-based feature selection and a symbiotic organism search nanoengineering were tested for their modeling performance with a nano-tumor dataset and nano-drugs for glioblastoma dataset, finding the latter the better algorithm. Incorporated into the method is the potential to adjust the drug delivery detection rate and drug delivery error detection rate of the learned method based on selected features determined by nano variational model decomposition for efficient drug delivery.


Assuntos
Glioblastoma , Nanopartículas , Nanoestruturas , Humanos , Sistemas de Liberação de Medicamentos , Nanotecnologia/métodos , Preparações Farmacêuticas , Nanopartículas/química
2.
Arch Oral Biol ; 162: 105944, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38492547

RESUMO

OBJECTIVE: Oral submucous fibrosis is a frequently reported potentially malignant disorder characterized by fibrosis and a malignant transformation rate of 7-30%. The role of hypoxia-inducible factor-1/2α in malignant transformation mechanisms of oral submucous fibrosis remains uncharted territory owing to a scarcity of studies. Thus the present systematic review and meta-analysis aimed to determine the role of hypoxia-inducible factor-1/2α in the progression of fibrosis of oral submucous fibrosis and its malignant transformation. MATERIAL AND METHODS: Using PubMed, Google Scholar, and Cochrane Library databases, full-text articles that investigated hypoxia-inducible factor-1/2α in oral submucous fibrosis were entailed for review. A modified Newcastle-Ottawa scale was employed to evaluate risk of bias in all articles and Review Manager was utilized for meta-analysis. RESULTS: Eighteen and eight qualified articles respectively were included for qualitative and quantitative data synthesis. Progressive upregulation of hypoxia-inducible factor-1/2α in oral submucous fibrosis is associated with fibrosis-induced carcinogenesis. A Random-effects model uncloaked that oral submucous fibrosis cases with significantly increased expression of hypoxia-inducible factor-1α had an increased associated risk of malignant transformation compared with controls (combined odds ratio 523.83, 95% confidence interval 125.74- 2182.28, p < 0.00001). CONCLUSION: The existing evidence substantiates the notion that hypoxia-inducible factor-1/2α, a fundamental pathogenetic mechanism of progression and malignant transformation of oral submucous fibrosis in the background of fibrosis.


Assuntos
Fibrose Oral Submucosa , Humanos , Fibrose Oral Submucosa/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia , Transformação Celular Neoplásica , Fibrose , Hipóxia
3.
Indian J Pathol Microbiol ; 66(4): 815-818, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38084538

RESUMO

Natural killer (NK) cells are one of the most important effector T -lymphocytes having antitumor effect. Only a few studies are present in the literature, correlating the expression of cluster of differentiation 57 (CD-57) in NK cells in oral squamous cell carcinoma (OSCC). To analyze the effect of the presence of NK cells in the stroma of OSCC and their effect on the tumor progression and prognosis. A retrospective study was performed over 122 OSCC patients who had undergone surgical treatment between 2014 and 16. Wax blocks were obtained and subjected to immunohistochemical (IHC) analysis for CD-57 expression. Patients were followed up for 3 years and 100 cases were finally included in the study and divided into three groups. The association between variable were studied through the Chi-square test, Kruskal-Wallis test, and Mann-Whitney U test. A total of 91% of cases showed positive staining for CD-57. Maximum positive expression (96.6%) was observed in the patients who were alive and without recurrence (Group-II) as compared to dead patients (Group-I) and in well-differentiated squamous cell carcinoma (WDSCC) cases (96.8%) than in poorly differentiated cases. Also, the mean CD-57 positive cells count was found to be highest in Group-II and WDSCC cases. A significant correlation was observed between CD-57 expression and patients' health status. As the expression of CD-57 increased in the tumor stroma of OSCC, the chances for the patient to be alive were increased; therefore, it may serve as a good prognostic marker.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estudos Retrospectivos , Imuno-Histoquímica
4.
J Maxillofac Oral Surg ; 22(3): 533-537, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37534343

RESUMO

Background: Maxillofacial tuberculosis is a diagnostic challenge for surgeons. The aim of this study was to present a detailed analysis of Xpert test in diagnosing maxillofacial tuberculosis and to analyse the accuracy of Xpert test results for various tissues of maxillofacial region. Materials and Methods: In this cross-sectional study, patients were selected randomly from outpatient department. The patients who had clinical picture and differential diagnosis highly suggestive of maxillofacial tuberculosis were included. Patients were divided into three different groups depending upon the site of involvement. The samples collected from the patients were further subdivided depending upon the type of specimen. Patients were screened first by routine tests, and the negative cases were followed by Xpert test for tuberculosis. Results: A total of 54 patients were enrolled in the study, 13 patients were found to be positive for maxillofacial tuberculosis on routine screening tests for tuberculosis, and 41 tested negative on routine test and were evaluated further through Xpert test. Specimens from bone (n12), soft tissue and skin biopsy (n15) and aspirates from lymph nodes (n14) were obtained and tested. Twenty-one samples were found to be positive, and 20 were negative upon Xpert testing. There was a statistically significant difference seen between the test groups (p < 0.01) with higher frequency of negative results in routine test. The p value for various specimens containing pus, biopsies and aspirates was 0.045, 0.023 and 0.067, respectively. Conclusion: Xpert test is more accurate when compared to routine test for diagnosing maxillofacial tuberculosis. Although accuracy of Xpert test is better for pus and biopsy samples in the specimens from bone and soft tissue, it gives poor accuracy for aspirated cells. The aspirates from lymph nodes were more susceptible for false negative test.

5.
Adv Cancer Res ; 159: 251-283, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37268398

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is the most common (∼90% cases) pancreatic neoplasm and one of the most lethal cancer among all malignances. PDAC harbor aberrant oncogenic signaling that may result from the multiple genetic and epigenetic alterations such as the mutation in driver genes (KRAS, CDKN2A, p53), genomic amplification of regulatory genes (MYC, IGF2BP2, ROIK3), deregulation of chromatin-modifying proteins (HDAC, WDR5) among others. A key event is the formation of Pancreatic Intraepithelial Neoplasia (PanIN) that often results from the activating mutation in KRAS. Mutated KRAS can direct a variety of signaling pathways and modulate downstream targets including MYC, which play an important role in cancer progression. In this review, we discuss recent literature shedding light on the origins of PDAC from the perspective of major oncogenic signaling pathways. We highlight how MYC directly and indirectly, with cooperation with KRAS, affect epigenetic reprogramming and metastasis. Additionally, we summarize the recent findings from single cell genomic approaches that highlight heterogeneity in PDAC and tumor microenvironment, and provide molecular avenues for PDAC treatment in the future.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Transdução de Sinais , Mutação , Microambiente Tumoral , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pancreáticas
6.
J Oral Maxillofac Pathol ; 27(Suppl 1): S41-S44, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37082279

RESUMO

Oncocytomas are one of the infrequent neoplasms seen in the oral cavity accounting for less than 2% of all neoplasms in the oral cavity with less than 1% chance of malignant transformation. They affect the major salivary glands and have a female predilection. The cognisance of the unique clinical and histopathological features is very important to conclude a confirmatory diagnosis. This paper reviews a case of oncocytoma presented in our department and also elucidates the diagnostic criteria for the same.

7.
J Cancer Res Ther ; 18(Supplement): S205-S209, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36510965

RESUMO

Background: The benign neoplasms are normally slow growing, indolent with no invasive potential. However, there exist a few locally aggressive benign odontogenic tumors that have a tendency to invade and deform the surrounding structures. The exact reason for the aggressiveness of these benign neoplasms remained an enigma. Their biology and clinical expression can often be destructive and ominous. An appropriate treatment protocol needs to be followed to combat the high recurrence rate and aggressiveness of these entities. Aggressive and noniaggressive epithelial odontogenic tumors were analyzed immunohistochemically with Ki-67 and glypican 3 (GPC3). Materials and Methods: Fifty-nine cases of tumors were divided into aggressive odontogenic tumors (20 solid ameloblastomas, four unicystic ameloblastoma, and 28 keratocystic odontogenic tumors) and nonaggressive odontogenic tumors (five adenomatoid odontogenic tumors and two calcifying cystic odontogenic itumors). Results: Statistical analysis using Pearson correlation showed Ki-67 to be a better marker for differentiating aggressive from nonaggressive odontogenic tumor as compared to GPC3 (P < 0.001, highly significant), whereas among aggressive tumors, GPC3 turned out to be more useful as compared to Ki-67 (P < 0.001, highly significant). Conclusion: The present study provides an insight into the different biological behavior of odontogenic tumors, which can thus be helpful in determining the therapy strategies for more aggressive odontogenic tumors.


Assuntos
Ameloblastoma , Cistos Odontogênicos , Tumores Odontogênicos , Humanos , Ameloblastoma/patologia , Glipicanas , Imuno-Histoquímica , Antígeno Ki-67 , Cistos Odontogênicos/patologia , Tumores Odontogênicos/patologia
8.
Cureus ; 14(5): e24801, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35686274

RESUMO

Interlocking nailing is a well-established procedure for managing unstable tibial shaft fractures. Closed reduction and internal fixation of the tibial shaft fractures require ease of intraoperative positioning, maneuvering, and biplane imaging. We describe the use of an innovative modular tibia-nailing stand, which greatly enhances the ergonomics of the tibia nailing procedure.

9.
Nat Chem Biol ; 18(5): 511-519, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35289328

RESUMO

Cone snail venoms contain a wide variety of bioactive peptides, including insulin-like molecules with distinct structural features, binding modes and biochemical properties. Here, we report an active humanized cone snail venom insulin with an elongated A chain and a truncated B chain, and use cryo-electron microscopy (cryo-EM) and protein engineering to elucidate its interactions with the human insulin receptor (IR) ectodomain. We reveal how an extended A chain can compensate for deletion of B-chain residues, which are essential for activity of human insulin but also compromise therapeutic utility by delaying dissolution from the site of subcutaneous injection. This finding suggests approaches to developing improved therapeutic insulins. Curiously, the receptor displays a continuum of conformations from the symmetric state to a highly asymmetric low-abundance structure that displays coordination of a single humanized venom insulin using elements from both of the previously characterized site 1 and site 2 interactions.


Assuntos
Insulina , Venenos de Moluscos , Microscopia Crioeletrônica , Humanos , Insulina/metabolismo , Venenos de Moluscos/química , Venenos de Moluscos/metabolismo , Peptídeos , Conformação Proteica
10.
Motor Control ; 26(1): 36-47, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34784587

RESUMO

Human rolling, as turning in bed, is a fundamental activity of daily living. A quantitative analysis of rolling could help identify the neuromusculoskeletal disorders that prohibit rolling and develop interventions for individuals who cannot roll. This study sought to determine whether crossing the arms over the chest would alter fundamental coordination patterns when rolling. Kinematic data were collected from 24 subjects as they rolled with and without their arms crossed over their chest. Crossing the arms decreased the mean peak angular velocities of the shoulders (p = .001) and pelvis (p = .013) and influenced the mean duration of the roll (p = .057). There were no fundamental differences in shoulder and pelvis coordination when rolling with the arms crossed over the chest, implying that the arms may not have a major role in rolling.


Assuntos
Ombro , Tronco , Braço , Fenômenos Biomecânicos , Humanos , Amplitude de Movimento Articular , Extremidade Superior
11.
Front Pharmacol ; 12: 681455, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483899

RESUMO

We investigated the effects of chronic oral administration of mineral oil, versus corn oil as control, on intestinal permeability, inflammatory markers, and plasma lipids in APOE*3-Leiden.CETP mice. Mice received mineral oil or corn oil 15 or 30 µL/mouse/day for 16 weeks (15 mice/group). Intestinal permeability was increased with mineral versus corn oil 30 µL/day, shown by increased mean plasma FITC-dextran concentrations 2 h post-administration (11 weeks: 1.5 versus 1.1 µg/ml, p = 0.02; 15 weeks: 1.7 versus 1.3 µg/ml, p = 0.08). Mean plasma lipopolysaccharide-binding protein levels were raised with mineral versus corn oil 30 µL/day (12 weeks: 5.8 versus 4.4 µg/ml, p = 0.03; 16 weeks: 5.8 versus 4.5 µg/ml, p = 0.09), indicating increased intestinal bacterial endotoxin absorption and potential pro-inflammatory effects. Plasma cholesterol and triglyceride concentrations were decreased with mineral oil, without affecting liver lipids among treated groups. Fecal neutral sterol measurements indicated increased fecal cholesterol excretion with mineral oil 30 µL/day (+16%; p = 0.04). Chronic oral administration of mineral oil in APOE*3-Leiden.CETP mice increased intestinal permeability, with potential pro-inflammatory effects, and decreased plasma cholesterol and triglyceride levels. Our findings may raise concerns about the use of mineral oil as a placebo in clinical studies.

12.
Am J Physiol Endocrinol Metab ; 321(1): E156-E163, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34056920

RESUMO

The brain has been traditionally thought to be insensitive to insulin, primarily because insulin does not stimulate glucose uptake/metabolism in the brain (as it does in classic insulin-sensitive tissues such as muscle, liver, and fat). However, over the past 20 years, research in this field has identified unique actions of insulin in the brain. There is accumulating evidence that insulin crosses into the brain and regulates central nervous system functions such as feeding, depression, and cognitive behavior. In addition, insulin acts in the brain to regulate systemic functions such as hepatic glucose production, lipolysis, lipogenesis, reproductive competence, and the sympathoadrenal response to hypoglycemia. Decrements in brain insulin action (or brain insulin resistance) can be observed in obesity, type 2 diabetes (T2DM), aging, and Alzheimer's disease (AD), indicating a possible link between metabolic and cognitive health. Here, we describe recent findings on the pleiotropic actions of insulin in the brain and highlight the precise sites, specific neuronal population, and roles for supportive astrocytic cells through which insulin acts in the brain. In addition, we also discuss how boosting brain insulin action could be a therapeutic option for people at an increased risk of developing metabolic and cognitive diseases such as AD and T2DM. Overall, this perspective article serves to highlight some of these key scientific findings, identify unresolved issues, and indicate future directions of research in this field that would serve to improve the lives of people with metabolic and cognitive dysfunctions.


Assuntos
Encéfalo/fisiologia , Insulina/fisiologia , Doença de Alzheimer , Ansiedade , Barreira Hematoencefálica/metabolismo , Peso Corporal , Encéfalo/efeitos dos fármacos , Colesterol/biossíntese , Cognição , Depressão , Ingestão de Alimentos , Glucose/biossíntese , Humanos , Insulina/metabolismo , Insulina/farmacologia , Metabolismo dos Lipídeos/fisiologia
13.
Eur J Pharm Sci ; 161: 105776, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33667667

RESUMO

We investigated the effects of mineral oil on statin pharmacokinetics and inflammatory markers in animal models. A new synthesis strategy produced regioisomers that facilitated the characterization of the main metabolite (M1) of atorvastatin, a lipophilic statin, in C57BL/6NCrl mice. The chemical structure of M1 in mice was confirmed as ortho-hydroxy ß-oxidized atorvastatin. Atorvastatin and M1 pharmacokinetics and inflammatory markers were assessed in C57BL6/J mice given atorvastatin 5 mg/kg/day or 10 mg/kg/day, as a single dose or for 21 days, with or without 10 µL or 30 µL mineral oil. No consistent differences in plasma exposure of atorvastatin or M1 were observed in mice after single or repeat dosing of atorvastatin with or without mineral oil. However, mice administered atorvastatin 10 mg/kg with 30 µL mineral oil for 21 days had significantly increased plasma levels of serum amyloid A (mean 9.6 µg/mL vs 7.9 µg/mL without mineral oil; p < 0.01) and significantly increased proportions of C62Lhigh B cells (mean 18% vs 12% without mineral oil; p = 0.04). There were no statistically significant differences for other inflammatory markers assessed. In dogs, pharmacokinetics of atorvastatin, its two hydroxy metabolites and pravastatin (a hydrophilic statin) were evaluated after single administration of atorvastatin 10 mg plus pravastatin 40 mg with or without 2 g mineral oil. Pharmacokinetics of atorvastatin, hydroxylated atorvastatin metabolites or pravastatin were not significantly different after single dosing with or without mineral oil in dogs. Collectively, the results in mice and dogs indicate that mineral oil does not affect atorvastatin or pravastatin pharmacokinetics, but could cause low-grade inflammation with chronic oral administration, which warrants further investigation.


Assuntos
Ácidos Heptanoicos , Inibidores de Hidroximetilglutaril-CoA Redutases , Animais , Atorvastatina , Cães , Camundongos , Camundongos Endogâmicos C57BL , Óleo Mineral , Pravastatina , Pirróis
14.
Front Bioinform ; 1: 693836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-36303746

RESUMO

Gene expression profiling techniques, such as DNA microarray and RNA-Sequencing, have provided significant impact on our understanding of biological systems. They contribute to almost all aspects of biomedical research, including studying developmental biology, host-parasite relationships, disease progression and drug effects. However, the high-throughput data generations present challenges for many wet experimentalists to analyze and take full advantage of such rich and complex data. Here we present GeneCloudOmics, an easy-to-use web server for high-throughput gene expression analysis that extends the functionality of our previous ABioTrans with several new tools, including protein datasets analysis, and a web interface. GeneCloudOmics allows both microarray and RNA-Seq data analysis with a comprehensive range of data analytics tools in one package that no other current standalone software or web-based tool can do. In total, GeneCloudOmics provides the user access to 23 different data analytical and bioinformatics tasks including reads normalization, scatter plots, linear/non-linear correlations, PCA, clustering (hierarchical, k-means, t-SNE, SOM), differential expression analyses, pathway enrichments, evolutionary analyses, pathological analyses, and protein-protein interaction (PPI) identifications. Furthermore, GeneCloudOmics allows the direct import of gene expression data from the NCBI Gene Expression Omnibus database. The user can perform all tasks rapidly through an intuitive graphical user interface that overcomes the hassle of coding, installing tools/packages/libraries and dealing with operating systems compatibility and version issues, complications that make data analysis tasks challenging for biologists. Thus, GeneCloudOmics is a one-stop open-source tool for gene expression data analysis and visualization. It is freely available at http://combio-sifbi.org/GeneCloudOmics.

15.
JAMA ; 324(22): 2268-2280, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33190147

RESUMO

Importance: It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk. Objective: To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk. Design, Setting, and Participants: A double-blind, randomized, multicenter trial (enrollment October 30, 2014, to June 14, 2017; study termination January 8, 2020; last patient visit May 14, 2020) comparing omega-3 CA with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). A total of 13 078 patients were randomized at 675 academic and community hospitals in 22 countries in North America, Europe, South America, Asia, Australia, New Zealand, and South Africa. Interventions: Participants were randomized to receive 4 g/d of omega-3 CA (n = 6539) or corn oil, which was intended to serve as an inert comparator (n = 6539), in addition to usual background therapies, including statins. Main Outcomes and Measures: The primary efficacy measure was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. Results: When 1384 patients had experienced a primary end point event (of a planned 1600 events), the trial was prematurely halted based on an interim analysis that indicated a low probability of clinical benefit of omega-3 CA vs the corn oil comparator. Among the 13 078 treated patients (mean [SD] age, 62.5 [9.0] years; 35% women; 70% with diabetes; median low-density lipoprotein [LDL] cholesterol level, 75.0 mg/dL; median triglycerides level, 240 mg/dL; median HDL-C level, 36 mg/dL; and median high-sensitivity C-reactive protein level, 2.1 mg/L), 12 633 (96.6%) completed the trial with ascertainment of primary end point status. The primary end point occurred in 785 patients (12.0%) treated with omega-3 CA vs 795 (12.2%) treated with corn oil (hazard ratio, 0.99 [95% CI, 0.90-1.09]; P = .84). A greater rate of gastrointestinal adverse events was observed in the omega-3 CA group (24.7%) compared with corn oil-treated patients (14.7%). Conclusions and Relevance: Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events. These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02104817.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Óleo de Milho/uso terapêutico , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Adulto , Colesterol/sangue , Método Duplo-Cego , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertrigliceridemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Triglicerídeos/sangue
16.
Natl J Maxillofac Surg ; 11(1): 67-75, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041580

RESUMO

OBJECTIVE: This study compared and evaluated the clinical and radiographic results of guided bone regeneration using platelet-rich fibrin (PRF) and collagen membrane as barrier membrane in immediately placed implants with severe buccal bone defect (with respect to marginal bone level, implant stability quotient [ISQ]), and histological analysis of new bone formation. MATERIALS AND METHODS: Sixteen implants were placed in patients requiring immediate implant placement and having a buccal wall defect and randomly divided into two groups one receiving PRF membranes and other collagen membrane. The sites were grafted with bone-substitute material in both the groups. After 4 months, at the time of second-stage surgery, implant stability is measured by Osstell Mentor, crestal bone level on mesial and distal sides of implant by digital intraoral periapical, buccal defect clinically by probe and histological analysis of biopsied bone. RESULTS: The results were insignificant and comparable in both the groups when comparison was made between the groups. The mean buccal defect, mean values of average ISQ, crestal bone level in both the groups at baseline and after 4 months were compared. No significant difference between both the groups was found after 4 months. Bone quality seemed to be equal in both groups after histological analysis. Within the limits of the study, both the groups had shown similar results in all criteria. CONCLUSION: Within the limitation of the study, it can be concluded that both the treatment modalities are successful in terms of buccal defect reduction, stability, and increase in crestal bone level.

17.
Mol Nutr Food Res ; 64(23): e2000788, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33063454

RESUMO

SCOPE: The influence of docosahexaenoic acid (DHA) on cardiometabolic and cognitive phenotypes, and multi-omic alterations in the brain under two metabolic conditions is explored to understand context-specific nutritional effects. METHODS AND RESULTS: Rats are randomly assigned to a DHA-rich or a control chow diet while drinking water or high fructose solution, followed by profiling of metabolic and cognitive phenotypes and the transcriptome and DNA methylome of the hypothalamus and hippocampus. DHA reduces serum triglyceride and improves insulin resistance and memory exclusively in the fructose-consuming rats. In hippocampus, DHA affects genes related to synapse functions in the chow group but immune functions in the fructose group; in hypothalamus, DHA alters immune pathways in the chow group but metabolic pathways in the fructose group. Network modeling reveals context-specific regulators of DHA effects, including Klf4 and Dusp1 for chow condition and Lum, Fn1, and Col1a1 for fructose condition in hippocampus, as well as Cyr61, JunB, Ier2, and Pitx2 under chow condition and Hcar1, Cdh1, and Osr1 under fructose condition in hypothalamus. CONCLUSION: DHA exhibits differential influence on epigenetic loci, genes, pathways, and metabolic and cognitive phenotypes under different dietary contexts, supporting population stratification in DHA studies to achieve precision nutrition.

19.
Nat Struct Mol Biol ; 27(7): 615-624, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32483339

RESUMO

Human insulin and its current therapeutic analogs all show propensity, albeit varyingly, to self-associate into dimers and hexamers, which delays their onset of action and makes blood glucose management difficult for people with diabetes. Recently, we described a monomeric, insulin-like peptide in cone-snail venom with moderate human insulin-like bioactivity. Here, with insights from structural biology studies, we report the development of mini-Ins-a human des-octapeptide insulin analog-as a structurally minimal, full-potency insulin. Mini-Ins is monomeric and, despite the lack of the canonical B-chain C-terminal octapeptide, has similar receptor binding affinity to human insulin. Four mutations compensate for the lack of contacts normally made by the octapeptide. Mini-Ins also has similar in vitro insulin signaling and in vivo bioactivities to human insulin. The full bioactivity of mini-Ins demonstrates the dispensability of the PheB24-PheB25-TyrB26 aromatic triplet and opens a new direction for therapeutic insulin development.


Assuntos
Antígenos CD/química , Insulina/química , Venenos de Moluscos/química , Venenos de Moluscos/metabolismo , Receptor de Insulina/química , Substituição de Aminoácidos , Animais , Antígenos CD/metabolismo , Sítios de Ligação , Cristalografia por Raios X , Insulina/análogos & derivados , Insulina/metabolismo , Insulina/farmacologia , Camundongos Endogâmicos C57BL , Modelos Moleculares , Simulação de Dinâmica Molecular , Venenos de Moluscos/genética , Venenos de Moluscos/farmacologia , Peptídeos/química , Peptídeos/genética , Peptídeos/metabolismo , Conformação Proteica , Ratos Sprague-Dawley , Receptor de Insulina/metabolismo , Relação Estrutura-Atividade , Tirosina
20.
J Clin Orthop Trauma ; 11(Suppl 2): S228-S233, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32189946

RESUMO

Background: Appropriate component sizing plays an important role in determining the functional outcome following total knee arthroplasty. Comparative studies of different populations have shown significant differences in the anthropometric parameters of knees in different race groups which negates the possibility of using a single sized implant system across different ethnic groups. This study evaluates the dimensions of femoral and tibial articular surfaces of Indian patients and compares the parameters with other ethnic groups and correlates the dimensions with five different commercially available knee systems.Material & Methods: Computerized tomography (CT) scans of contralateral normal knees of patients who underwent the scan for various ailments of the knee were retrieved retrospectively from the hospital database and 3D reconstruction of the images was done. Mediolateral dimensions (fML,tML), Anteroposterior dimensions (fAP, tAP) and aspect ratio (fML/fAP, tML/tAP) of the femur and tibia respectively were calculated and compared with the dimensions of different ethnic groups as well as the femoral and tibial components of five different knee prosthesis systems. RESULTS: The average fML in the study group was less than that of Caucasian knees but was marginally larger than other ethnic groups. The fAP, tML and tAP was found to be smaller than all other ethnic groups but a larger femoral aspect ratio was reported than other ethnic groups. Among the implant systems, only NexGen LPS and Scorpio NRG implant femoral components closely matched the femoral dimensions in the study group whereas all implant systems showed significant mismatch with tibial component dimensions when compared to the study populations. CONCLUSION: This study concludes that the dimensions of Indian knees are different from other ethnic groups and the use of commercially available knee Implants designed based on measurements in Caucasian populations can lead to significant mismatch between implant and resected bone surfaces.

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