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1.
Foods ; 13(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38611325

RESUMO

A significant fraction of the food produced worldwide is currently lost or wasted throughout the supply chain, squandering natural and economic resources. Food waste valorization will be an important necessity in the coming years. This work investigates the ability of food waste to serve as a viable nutritional substrate for the heterotrophic growth of Chlorella vulgaris. The impact of different pretreatments on the elemental composition and microbial contamination of seven retail food waste mixtures was evaluated. Among the pretreatment methods applied to the food waste formulations, autoclaving was able to eliminate all microbial contamination and increase the availability of reducing sugars by 30%. Ohmic heating was also able to eliminate most of the contaminations in the food wastes in shorter time periods than autoclave. However, it has reduced the availability of reducing sugars, making it less preferable for microalgae heterotrophic cultivation. The direct utilization of food waste containing essential nutrients from fruits, vegetables, dairy and bakery products, and meat on the heterotrophic growth of microalgae allowed a biomass concentration of 2.2 × 108 cells·mL-1, being the culture able to consume more than 42% of the reducing sugars present in the substrate, thus demonstrating the economic and environmental potential of these wastes.

2.
Nat Commun ; 14(1): 2779, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37188705

RESUMO

Reversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood-brain barrier. Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their glucose tolerance, liver steatosis and insulin sensitivity after treatment with harmol. Harmol or a combination of monoamine oxidase B and GABA-A receptor modulators extend the lifespan of hermaphrodite Caenorhabditis elegans or female Drosophila melanogaster. Finally, two-year-old male and female mice treated with harmol exhibit delayed frailty onset with improved glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis.


Assuntos
Envelhecimento , Antidepressivos , Harmina , Mitocôndrias , Mitofagia , Monoaminoxidase , Receptores de GABA-A , Harmina/análogos & derivados , Harmina/farmacologia , Antidepressivos/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Quinases Proteína-Quinases Ativadas por AMP/metabolismo , Músculo Esquelético/efeitos dos fármacos , Fígado/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Resistência à Insulina , Intolerância à Glucose/metabolismo , Estado Pré-Diabético/metabolismo , Monoaminoxidase/metabolismo , Receptores de GABA-A/metabolismo , Longevidade/efeitos dos fármacos , Caenorhabditis elegans , Drosophila melanogaster , Fragilidade/prevenção & controle , Condicionamento Físico Animal , Modelos Animais , Masculino , Feminino , Animais , Camundongos , Fígado Gorduroso/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos
3.
Diabetes Res Clin Pract ; 198: 110623, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36907358

RESUMO

AIMS: This study aimed to identify demographic, clinical, and psychological contributors to DFU healing and favorable healing process. METHODS: Patients with a chronic DFU were evaluated at baseline (T0; n = 153), two months later (T1; n = 108), and six months later (T2; n = 71). Patients were evaluated on health literacy, perceived stress, anxiety, depression, and illness perceptions. Cox proportional hazard models were built to analyze the predictors of DFU healing and favorable healing process (wound area reduction), including the assessment of time to achieve those outcomes. RESULTS: More than half of patients had their DFU healed (56.1%) or showed a favorable healing process (83.6%). Median time for healing was 112 days, while for favorable process was 30 days. Illness perceptions were the only predictor of wound healing. Being female , with adequate health literacy, and a first DFU predicted a favorable healing process. CONCLUSIONS: This is the first study showing that beliefs about DFU are significant predictors of DFU healing, and that health literacy is a significant predictor of a favorable healing process. Brief, comprehensive interventions should be implemented, at the treatment initial stage, in order to change misperceptions and to promote DFU literacy and better health outcomes.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Feminino , Masculino , Pé Diabético/tratamento farmacológico , Cicatrização , Modelos de Riscos Proporcionais , Fatores de Tempo
5.
Knee Surg Sports Traumatol Arthrosc ; 31(9): 3637-3645, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34409552

RESUMO

PURPOSE: The relationship between osteotomies around the knee and ankle alignment has been well established. However, little is known about the incidence of new-onset ankle pain after knee osteotomies in the setting of both varus and valgus lower limb malalignments. The purpose of this study is to determine the incidence and characteristics of ankle pain after knee osteotomies; and to clarify the relationship between knee alignment correction, coronal changes suffered by the ankle joint and the development of new-onset ankle pain. METHODS: Fifty-four lower limbs in 51 consecutive patients, who underwent realignment osteotomies around the knee between April 2013 and October 2020, were retrospectively reviewed. Ultimately, 39 patients (42 knees) were enrolled: 34 had varus deformities and eight had valgus deformities. Ankle pain was assessed according to the Numerical Pain Rating Scale by telephonic interview. The magnitude of alignment correction and the consequent change of both knee and ankle joint lines were analyzed. Correlation between the former and the onset of post-operative ankle pain was evaluated. Patient satisfaction and complications were also noted. RESULTS: The incidence of new-onset ankle pain after knee realignment osteotomy was 14%, at a mean follow-up of 55 ± 26 months (range 12-93 months). The mean time between osteotomy and onset of ankle pain was 21 ± 25 months (range 2-60 months). The degree of coronal correction was significantly correlated with ankle joint obliquity changes. However, a significant correlation with post-operative ankle pain was not found (p > 0.05). CONCLUSION: Fourteen percent of the patients who underwent osteotomies around the knee developed new-onset persistent low-intensity ankle pain. The knee and ankle joint biomechanics are closely related, however, only a small percentage of patients suffer from low-intensity ankle pain which is successfully managed with occasional analgesics. Most osteotomies around the knee seem to require no particular concern for the ipsilateral ankle function.


Assuntos
Articulação do Tornozelo , Tornozelo , Humanos , Tornozelo/cirurgia , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Estudos Retrospectivos , Tíbia/cirurgia , Articulação do Joelho/cirurgia , Extremidade Inferior , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Osteotomia/efeitos adversos
6.
Br J Nutr ; 129(3): 395-405, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35506448

RESUMO

Colorectal cancer is the third most diagnosed cancer worldwide and linked to dietary/lifestyle factors. Arthrospira (Spirulina) platensis (AP) contains bioactive compounds with beneficial effects in vivo/in vitro. We evaluated the effects of AP feeding against 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Male Sprague Dawley rats were given subcutaneous injections of DMH (4 × 40 mg/kg body weight) (G1-G3) or vehicle (G4-G5) twice a week (weeks 3-4). During weeks 1-4, animals were fed a diet containing 1 % (G2) or 2 % (G3-G4) AP powder (w/w). After this period, all groups received a balanced diet until week 12. Some animals were euthanised after the last DMH injection (week 4) for histological, immunohistochemical (Ki-67, γ-H2AX and caspase-3) and molecular analyses (real time-PCR for 91 genes), while other animals were euthanised at week 12 for preneoplastic aberrant crypt foci (ACF) analysis. Both AP treatments (G2-G3) significantly decreased the DMH-induced increase in γ-H2AX (DNA damage) and caspase 3 (DNA damage-induced cell death) in colonic crypts at week 4. In addition, Cyp2e1 (Drug metabolism), Notch1, Notch2 and Jag1 genes (Notch pathway) and Atm, Wee1, Chek2, Mgmt, Ogg1 and Xrcc6 genes (DNA repair) were also down-regulated by 2 % AP feeding (G3) at week 4. A significant reduction in ACF development was observed in both AP-treated groups (G2-G3) at week 12. In conclusion, findings indicate that AP feeding reduced acute colonic damage after DMH, resulting in fewer preneoplastic lesions. Our study provided mechanistic insights on dietary AP-preventive effects against early colon carcinogenesis.


Assuntos
Focos de Criptas Aberrantes , Neoplasias do Colo , Lesões Pré-Cancerosas , Spirulina , Ratos , Animais , Masculino , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/prevenção & controle , 1,2-Dimetilidrazina/toxicidade , Ratos Sprague-Dawley , Carcinogênese/patologia , Colo , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/prevenção & controle , Carcinógenos/toxicidade , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/prevenção & controle
7.
Plant Foods Hum Nutr ; 78(1): 93-99, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36334234

RESUMO

Capsaicin (CAP) is the compound responsible for pungency in chili peppers, presenting several biological properties. But its general safety and effectiveness in the context of carcinogenesis has not been fully clarified. Thus, the present study evaluated whether dietary CAP modifies the development of urothelial lesions induced by the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male Sprague-Dawley rats. Animals were randomly allocated into 6 groups: G1 - treated with 0.05% BBN in drinking water (weeks 1-12) and received a balanced diet (weeks 1-20); G2 and G3-treated with BBN (weeks 1-12) and received a balanced diet with 0.01 or 0.02% CAP (weeks 1-20), respectively; G4 and G5- only received a balanced diet with 0.01 or 0.02% CAP (weeks 1-20), respectively; G6 - only received a balanced diet (weeks 1-20). At the end of week 20, the incidence and types of urothelial lesions, proliferating cell nuclear antigen (PCNA) labeling index, and matrix metalloproteinases (MMP) 2 and 9 activities were analyzed. A significant reduction was observed in the incidence and multiplicity of simple (p = 0.020 and p = 0.011) and nodular/papillary (p = 0.030 and p = 0.003) hyperplasias and papillomas/carcinomas (p = 0.023 and p = 0.020), epithelial proliferation (p = 0.007) and in the activity of the intermediate form of MMP-2 (p < 0.001) and pro-MMP-9 activities (p < 0.002), in BBN + 0.02% CAP (G3) group in comparison to BBN (G1) group. Capsaicin intake per se did not alter body weight, liver and kidney weights, urothelial histology or serum biochemical parameters. Thus, dietary CAP was safe and showed a protective effect against rat BBN-induced urothelial carcinogenesis.


Assuntos
Neoplasias da Bexiga Urinária , Ratos , Animais , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Capsaicina/farmacologia , Ratos Sprague-Dawley , Carcinógenos/farmacologia , Carcinogênese/patologia , Dieta
8.
Histol Histopathol ; : 18692, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38179656

RESUMO

Globally, colorectal cancer (CRC) is one of the most frequently diagnosed human gastrointestinal neoplasia and the second leading cause of cancer-related death in both men and women. Despite considerable efforts currently devoted to the study of the biology and treatment of CRC, patient prognosis and survival are still poor. Sporadic CRC is a complex multistep disease and usually emerges in the setting of lifestyle and dietary changes mainly observed in industrialized countries with high human development index (HDI) (westernized style). The molecular pathogenesis of sporadic CRC presents genetic heterogeneity with APC, RAS, PIK3CA, TGFBR, SMAD4, and TP53 mutations usually detected during the progression of this malignancy. The establishment of sporadic CRC models has become essential for both basic and translational research to improve our understanding of the pathophysiology, unravel new molecular drivers, and preventive/therapeutic improvement of this malignancy. Chemically induced rodent models of sporadic CRC recapitulate most key morphological and genetic/epigenetic events observed during the promotion and progression of this malignancy, establishing effective diagnostic and prevention strategies to be translated into clinical practice. The present review gathers the main features of the state-of-the-art evidence on chemically induced rodent models, widely applied for translational modelling of sporadic CRC with a specific focus on histopathology and prevention perspectives. Our narrative review reinforces the persistent value of these bioassays and encourages the use of multimodel strategies for further investigations.

9.
Nat Commun ; 13(1): 5677, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36167809

RESUMO

Fasting exerts beneficial effects in mice and humans, including protection from chemotherapy toxicity. To explore the involved mechanisms, we collect blood from humans and mice before and after 36 or 24 hours of fasting, respectively, and measure lipid composition of erythrocyte membranes, circulating micro RNAs (miRNAs), and RNA expression at peripheral blood mononuclear cells (PBMCs). Fasting coordinately affects the proportion of polyunsaturated versus saturated and monounsaturated fatty acids at the erythrocyte membrane; and reduces the expression of insulin signaling-related genes in PBMCs. When fasted for 24 hours before and 24 hours after administration of oxaliplatin or doxorubicin, mice show a strong protection from toxicity in several tissues. Erythrocyte membrane lipids and PBMC gene expression define two separate groups of individuals that accurately predict a differential protection from chemotherapy toxicity, with important clinical implications. Our results reveal a mechanism of fasting associated with lipid homeostasis, and provide biomarkers of fasting to predict fasting-mediated protection from chemotherapy toxicity.


Assuntos
Jejum , MicroRNAs , Animais , Biomarcadores , Doxorrubicina/toxicidade , Jejum/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos Monoinsaturados , Homeostase , Humanos , Insulina , Leucócitos Mononucleares/metabolismo , Camundongos , Oxaliplatina
10.
Int J Oral Maxillofac Implants ; 37(4): 812-822, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35904839

RESUMO

PURPOSE: To observe whether the initial implant stability, evaluated by two different methods-the insertion torque value (ITV) and implant stability quotient (ISQ)-may be influenced by different clinical conditions as well as to understand whether it is possible to establish an overall positive correlation between both methods and whether the obtained correlation is maintained for each clinical variable under scope. MATERIALS AND METHODS: The initial implant stability was evaluated by assessing and recording the ITV and the ISQ for each implant included in the study. The independent evolution of each method was observed considering clinical conditions grouped by gender (male or female), age (≤ 60 or > 60 years), arch (mandible or maxilla), location (incisors, canines and premolars, or molars), implant geometry (aggressive tapered or traditional parallel), diameter (3.5, 3.75, 4.3, or 5 mm), length (≥ 10 or < 10 mm), and immediate implantation (yes or no). The Mann-Whitney-Wilcoxon and Kruskal-Wallis localization tests were used to identify intragroup differences. To determine the level of correlation between both methods, the Spearman rank correlation was used. RESULTS: The intragroup comparisons showed that the mandible (P = .03), short implants (P = .03), and delayed implantation (P = .07) subgroups exhibited higher ITVs. The other groups did not show significant differences. The higher ISQ measurements were obtained in the mandible (P = .0002), younger patients (P = .02), diameters of 3.75 mm and 4.3 mm (P = .04), and delayed implantation (P < .0001) subgroups. No differences were found for the other groups. A strong overall correlation (rho = 0.541; P = 8.023e-06) was found between both methods for ITVs up to 40 Ncm once they were accompanied by a linear increase in the ISQ to a value up to 78. From this value, the overall correlation decreased (rho = 0.237; P = .0055). Regarding the clinical conditions, different levels of significant correlations were found for both genders, older patients, maxilla, molar area, aggressive tapered implant geometries, diameters of 4.3 mm, diameters of 5 mm, lengths ≥ 10 mm, and implants placed in healed bone. The other clinical conditions under scope did not exhibit an important correlation between both methods. CONCLUSION: When analyzed separately, clinical conditions such as the arch, implant length and diameter, patient age, and timing of implantation showed an influence on the ITV and the ISQ. An important overall correlation between both methods was found for ITVs of ≤ 40 Ncm. This correlation was maintained for several of the clinical conditions studied.


Assuntos
Implantes Dentários , Animais , Dente Pré-Molar/cirurgia , Implantação Dentária Endóssea/métodos , Feminino , Masculino , Mandíbula/cirurgia , Maxila/cirurgia , Torque
11.
Math Biosci Eng ; 19(7): 6435-6454, 2022 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-35730265

RESUMO

Generalized additive models provide a flexible and easily-interpretable method for uncovering a nonlinear relationship between response and covariates. In many situations, the effect of a continuous covariate on the response varies across groups defined by the levels of a categorical variable. When confronted with a considerable number of groups defined by the levels of the categorical variable and a factor-by-curve interaction is detected in the model, it then becomes important to compare these regression curves. When the null hypothesis of equality of curves is rejected, leading to the clear conclusion that at least one curve is different, we may assume that individuals can be grouped into a number of classes whose members all share the same regression function. We propose a method that allows determining such groups with an automatic selection of their number by means of bootstrapping. The validity and behavior of the proposed method were evaluated through simulation studies. The applicability of the proposed method is illustrated using real data from an experimental study in neurology.


Assuntos
Córtex Pré-Frontal , Projetos de Pesquisa , Simulação por Computador , Humanos , Modelos Estatísticos
12.
J Ment Health ; 31(6): 792-800, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33100065

RESUMO

BACKGROUND: One of the most serious complications of diabetes mellitus (DM) is a diabetic foot ulcer (DFU), with lower extremity amputation (LEA). AIMS: This study aims to explore the role of anxiety and depression on mortality, reamputation and healing, after a LEA due to DFU. METHODS: A sample of 149 patients with DFU who underwent LEA answered the Hospital Anxiety and Depression Scale and a sociodemographic and clinical questionnaire. This is a longitudinal and multicenter study with four assessment moments that used Cox proportional hazards models adjusted for demographic and clinical variables. RESULTS: Rate of mortality, reamputation and healing, 10 months after LEA were 9.4%, 27.5% and 61.7%, respectively. Anxiety, at baseline, was negatively associated with healing. However, depression was not an independent predictor of mortality. None of the psychological factors was associated with reamputation. CONCLUSION: Results highlight the significant contribution of anxiety symptoms at pre-surgery, to healing after a LEA. Suggestions for psychological interventions are made.


Assuntos
Amputação Cirúrgica , Pé Diabético , Humanos , Pé Diabético/cirurgia , Ansiedade , Transtornos de Ansiedade , Fatores de Risco
13.
BMC Ecol Evol ; 21(1): 210, 2021 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809580

RESUMO

BACKGROUND: The contribution of North Africa to the assembly of biodiversity within the Western Palaearctic is still poorly documented. Since the Miocene, multiple biotic exchanges occurred across the Strait of Gibraltar, underlying the high biogeographic affinity between the western European and African sides of the Mediterranean basin. We investigated the biogeographic and demographic dynamics of two large Mediterranean-adapted snakes across the Strait and assess their relevance to the origin and diversity patterns of current European and North African populations. RESULTS: We inferred phylogeographic patterns and demographic history of M. monspessulanus and H. hippocrepis, based on range-wide multilocus data, combined with fossil data and species distribution modelling, under present and past bioclimatic envelopes. For both species we identified endemic lineages in the High Atlas Mountains (Morocco) and in eastern Iberia, suggesting their persistence in Europe during the Pleistocene. One lineage is shared between North Africa and southern Iberia and likely spread from the former to the latter during the sea-level low stand of the last glacial stage. During this period M. monspessulanus shows a sudden demographic expansion, associated with increased habitat suitability in North Africa. Lower habitat suitability is predicted for both species during interglacial stages, with suitable areas restricted to coastal and mountain ranges of Iberia and Morocco. Compiled fossil data for M. monspessulanus show a continuous fossil record in Iberia at least since the Pliocene and throughout the Pleistocene. CONCLUSIONS: The previously proposed hypothesis of Pleistocene glacial extinction of both species in Europe is not supported based on genetic data, bioclimatic envelopes models, and the available fossil record. A model of range retraction to mountain refugia during arid periods and of glacial expansion (demographic and spatial) associated to an increase of Mediterranean habitats during glacial epochs emerges as a general pattern for mesic vertebrates in North Africa. Moreover, the phylogeographic pattern of H. hippocrepis conforms to a well-established biogeographic partition between western and eastern Maghreb.


Assuntos
Colubridae , Variação Genética , Animais , Demografia , Gibraltar , Filogenia
14.
Int J Implant Dent ; 7(1): 81, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467461

RESUMO

BACKGROUND: Crown-to-implant ratio and crown height space, associated with the use of short implants, have been related with marginal bone loss. However, it is unclear which of the two entities would play the most important role on the bone remodelling process. Using a finite element analysis, the present work aims to help clarifying how those two factors contribute for the stress generation at the marginal bone level. A numerical model (reference model), with a crown-to-implant ratio of 4, was double validated and submitted to a numerical calculation. Then, it was modified in two different ways: (a) by decreasing the prosthetic height obtaining crown-to-implant ratios of 3, 2.5 and 2 and (b) by increasing the implants length obtaining a crown-to-implant ratio of 2.08. The new models were also submitted to numerical calculations. RESULTS: The reference model showed a marginal bone stress of 96.9 MPa. The increase in the implants' length did not show statistically significant differences in the marginal bone stress (p-value = 0.2364). The decrease in the prosthetic height was accompanied with a statistically significant decrease in the marginal bone stresses (p-value = 2.2e- 16). CONCLUSIONS: The results represent a paradigm change as the crown height space appears to be more responsible for marginal bone stress than the high crown-to-implant ratios or the implants' length. New prosthetic designs should be attempted to decrease the stress generated at the marginal bone level.


Assuntos
Coroas , Análise de Elementos Finitos , Estresse Mecânico
15.
Phys Rev E ; 103(4-1): 042904, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34005892

RESUMO

We propose a granular architecture as a potential impact protector and signal filter. The system consists of monodispersed granular chains decorated with side beads fixed (welded) on sidewalls. Numerical results from usual monodispersed chains and simple tapered chains are employed as reference. An appropriate material combination and an optimal radii ratio between the side and axial granules show that more than 90% of the momentum amplitude of solitary pulses can be attenuated using a small and scalable system composed of five axial granules. Considering sinusoidal signals, the findings suggest that regular chains (monodispersed and tapered) are low-pass filters with cutoff frequencies as functions of the driven amplitude, restitutional losses, and tapering. The granular chain with fixed decoration filters all the input signals.

16.
J Transl Autoimmun ; 4: 100099, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997753

RESUMO

Pyoderma gangrenosum manifests as an ulceration of the skin often associated with several systemic diseases. The diagnosis is usually made by exclusion criteria with suggestions made by clinical findings and histological features. It can occur any site but more common in the legs. Advances in translational medicine led to the development of new forms of therapy in chronic inflammatory diseases by the oral administration of Janus kinase inhibitors. We report two cases of chronic ulceration of the skin consistent with the diagnosis of Pyoderma Gangrenosum that went into complete remission after the use of baricitinib.

17.
Cell Rep ; 34(11): 108851, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33730574

RESUMO

Devil facial tumor disease (DFTD) and its lack of available therapies are propelling the Tasmanian devil population toward extinction. This study demonstrates that cholesterol homeostasis and carbohydrate energy metabolism sustain the proliferation of DFTD cells in a cell-type-dependent manner. In addition, we show that the liver-X nuclear receptor-ß (LXRß), a major cholesterol cellular sensor, and its natural ligand 24S-hydroxycholesterol promote the proliferation of DFTD cells via a metabolic switch toward aerobic glycolysis. As a proof of concept of the role of cholesterol homeostasis on DFTD proliferation, we show that atorvastatin, an FDA-approved statin-drug subtype used against human cardiovascular diseases that inhibits cholesterol synthesis, shuts down DFTD energy metabolism and prevents tumor growth in an in vivo DFTD-xenograft model. In conclusion, we show that intervention against cholesterol homeostasis and carbohydrate-dependent energy metabolism by atorvastatin constitutes a feasible biochemical treatment against DFTD, which may assist in the conservation of the Tasmanian devil.


Assuntos
Colesterol/metabolismo , Neoplasias Faciais/metabolismo , Neoplasias Faciais/veterinária , Homeostase , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Receptores X do Fígado/metabolismo , Marsupiais/metabolismo , Aerobiose/efeitos dos fármacos , Animais , Atorvastatina/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Faciais/patologia , Feminino , Glicólise/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oxisteróis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Mol Phylogenet Evol ; 155: 106969, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33031930

RESUMO

Plate tectonics constitute one of the main mechanisms of biological diversification on Earth, often being associated with cladogenetic events at different phylogenetic levels, as well as with exchange of faunas and floras across previously isolated biogeographic regions. North Africa and Arabia share a complex geological history that dates back to the break-up of the Arabian plate from the African plate ~30-25 Mya, followed by various geological events, such as the formation of the Red Sea or the connection between the African, Arabian and Eurasian plates. Species with Saharo-Arabian distributions have shown a close association between their evolutionary history and these geological events. In this study, we investigate the systematics, biogeography and evolution of the genus Tropiocolotes, a group of small ground-dwelling geckos, comprised by 12 species distributed from the Atlantic coast of North Africa to southwestern Iran. Species delimitation analyses uncovered the existence of high levels of undescribed diversity, with forms here considered at the species level including Tropiocolotes tripolitanus (Mauritania and southern Morocco), T. nattereri (southern Israel) and T. scorteccii (Yemen and Oman). Phylogenetic and biogeographic analyses recovered two main clades, an exclusively African clade and a Saharo-Arabian clade, that split ~25 Mya following the vicariant event mediated by the separation of the Arabian and African plates. The complex geological activity around the Red Sea is associated with the diversification within the Saharo-Arabian clade, including the colonization of North Africa from a second Tropiocolotes group. Results also provide new insights into the geographic distribution of Tropiocolotes nubicus, previously considered as exclusively associated to the Nile River valley, extending its known distribution further west, up to the Central Mountains of the Sahara. Accordingly, the Nile River seems to act as a major biogeographic barrier, separating Tropiocolotes nubicus and T. steudneri in their western and eastern margins, respectively.


Assuntos
Evolução Biológica , Lagartos/classificação , Filogeografia , África do Norte , Animais , Teorema de Bayes , Haplótipos/genética , Funções Verossimilhança , Filogenia , Especificidade da Espécie , Fatores de Tempo
19.
Nutr Cancer ; 73(5): 817-828, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32400193

RESUMO

Capsaicin (CPS), an ingredient of Capsicum plants, has anti-inflammatory, antioxidant and antitumoral properties. The mechanisms of CPS on hepatocarcinogenesis preclinical bioassays are not described. Thus, the protective effects CPS were evaluated in the early stages of chemically-induced hepatocarcinogenesis. Male Wistar rats received diet containing 0.01% or 0.02% CPS for 3 weeks. Afterwards, animals received a dose of hepatocarcinogen diethylnitrosamine (DEN, 100 mg/kg body weight). From weeks 4-12, groups had their diet replaced by a 0.05% phenobarbital supplemented one to promote DEN-induced preneoplastic lesions. Animals were euthanized 24 h after DEN administration (n = 5/group) or at week 12 (n = 9/group). The estimated CPS intake in rats resembled human consumption. At the end of week 3, dietary 0.02% CPS attenuated DEN-induced oxidative damage and, consequently, hepatocyte necrosis by reducing serum alanine aminotransferase levels, liver CD68-positive macrophages, lipid peroxidation, while increasing antioxidant glutathione system. Additionally, 0.02% CPS upregulated vanilloid Trpv1 receptor and anti-inflammatory epoxygenase Cyp2j4 genes in the liver. Ultimately, previous 0.02% CPS intake decreased the number of GST-P-positive preneoplastic lesions at week 12. Thus, CPS attenuated preneoplastic lesion development, primarily by diminishing DEN-induced oxidative liver injury. Findings indicate that CPS is a promising chemopreventive agent when administered after and during the early stages of hepatocarcinogenesis.


Assuntos
Capsaicina , Neoplasias Hepáticas Experimentais , Animais , Capsaicina/farmacologia , Família 2 do Citocromo P450 , Dieta , Dietilnitrosamina/toxicidade , Glutationa Transferase , Fígado , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/prevenção & controle , Masculino , Ratos , Ratos Wistar
20.
J Child Orthop ; 15(6): 532-539, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34987662

RESUMO

PURPOSE: Distal radius fractures represent one of the most common fractures in children. Our purpose is to analyze risk factors for redisplacement in children with distal radius fractures treated by means of closed reduction and plaster cast immobilization. METHODS: Retrospective study, including children under the age of 17 years, who underwent closed manipulation and cast immobilization for a distal third radius fracture, between 2012 and 2015. Preoperative radiographs were reviewed for initial translation, angulation and shortening, distance of the fracture from the physis, degree of fracture obliquity and the presence of an ulna fracture. Postoperative radiographs were analyzed for translation, angulation and shortening, as well as the quality of closed reduction. Cast index, gap index and three-point index, were measured on the postoperative radiographs. Redisplacement and re-intervention during follow-up were registered. RESULTS: A total of 26 patients were included in this study. Comparison between post-reduction and immediate post-cast removal radiographs did not show any statistically significant difference between translation or shortening. Coronal (p = 0.002) and sagittal (p = 0.002) angulation showed a statistically significant difference, but both median values remained below cut-off values for redisplacement. Redisplacement was observed in four patients. Only one patient underwent remanipulation. All four had full remodelling and proper radiological alignment at final follow-up. Quality of reduction was found to be a statistically significant risk factor for redisplacement (p = 0.013). CONCLUSION: Closed reduction and cast immobilization under general anaesthesia yields good results in the treatment of distal forearm fractures in paediatric patients. Quality of reduction was the only risk factor that we found to be predictive of redisplacement. LEVEL OF EVIDENCE: Level III - Retrospective comparative study.

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