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The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein. In addition, Peroxyredoxin 3 (PRXIII) protein decreased by 50 %, which on overall suggested the absence of induction of mitochondrial biogenesis by RSV in old Sol. A novel direct correlation between PGC-1α and PRXIII proteins was demonstrated by correlation analysis in RSV and ad-libitum (AL) rats, supporting the reciprocally coordinated expression of the proteins. RSV supplementation led to an unexpected 50 % increase in the frequency of the oxidized base OH8dG in mtDNA. Furthermore, RSV supplementation induced a 50 % increase in the DRP1 protein of mitochondrial dynamics. In both rat groups an inverse correlation between PGC-1α and the frequency of OH8dG as well as an inverse correlation between PRXIII and the frequency of OH8dG were also found, suggestive of a relationship between oxidative damage to mtDNA and mitochondrial biogenesis activity. Such results may indicate that the antioxidant activity of RSV in aged Sol impinged on the oxidative fiber-specific, ROS-mediated, retrograde communication, thereby affecting the expression of SIRT1, PGC-1α and PRXIII, reducing the compensatory responses to the age-related mitochondrial oxidative stress and decline.
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Envelhecimento , Mitocôndrias Musculares , Músculo Esquelético , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Ratos Wistar , Resveratrol , Sirtuína 1 , Animais , Resveratrol/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Masculino , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/metabolismo , Mitocôndrias Musculares/efeitos dos fármacos , Mitocôndrias Musculares/metabolismo , Ratos , Estilbenos/farmacologia , Antioxidantes/farmacologia , Peroxirredoxinas/metabolismo , DNA Mitocondrial/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Dinaminas/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacosRESUMO
Mitochondria play a key role in cancer and their involvement is not limited to the production of ATP only. Mitochondria also produce reactive oxygen species and building blocks to sustain rapid cell proliferation; thus, the deregulation of mitochondrial function is associated with cancer disease development and progression. In cancer cells, a metabolic reprogramming takes place through a different modulation of the mitochondrial metabolic pathways, including oxidative phosphorylation, fatty acid oxidation, the Krebs cycle, glutamine and heme metabolism. Alterations of mitochondrial homeostasis, in particular, of mitochondrial biogenesis, mitophagy, dynamics, redox balance, and protein homeostasis, were also observed in cancer cells. The use of drugs acting on mitochondrial destabilization may represent a promising therapeutic approach in tumors in which mitochondrial respiration is the predominant energy source. In this review, we summarize the main mitochondrial features and metabolic pathways altered in cancer cells, moreover, we present the best known drugs that, by acting on mitochondrial homeostasis and metabolic pathways, may induce mitochondrial alterations and cancer cell death. In addition, new strategies that induce mitochondrial damage, such as photodynamic, photothermal and chemodynamic therapies, and the development of nanoformulations that specifically target drugs in mitochondria are also described. Thus, mitochondria-targeted drugs may open new frontiers to a tailored and personalized cancer therapy.
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Mitocôndrias , Neoplasias , Humanos , Mitocôndrias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Fosforilação Oxidativa , Ciclo do Ácido Cítrico , Oxirredução , Espécies Reativas de Oxigênio/metabolismoRESUMO
Mitochondria and mitochondrial proteins represent a group of promising pharmacological target candidates in the search of new molecular targets and drugs to counteract the onset of hypertension and more in general cardiovascular diseases (CVDs). Indeed, several mitochondrial pathways result impaired in CVDs, showing ATP depletion and ROS production as common traits of cardiac tissue degeneration. Thus, targeting mitochondrial dysfunction in cardiomyocytes can represent a successful strategy to prevent heart failure. In this context, the identification of new pharmacological targets among mitochondrial proteins paves the way for the design of new selective drugs. Thanks to the advances in omics approaches, to a greater availability of mitochondrial crystallized protein structures and to the development of new computational approaches for protein 3D-modelling and drug design, it is now possible to investigate in detail impaired mitochondrial pathways in CVDs. Furthermore, it is possible to design new powerful drugs able to hit the selected pharmacological targets in a highly selective way to rescue mitochondrial dysfunction and prevent cardiac tissue degeneration. The role of mitochondrial dysfunction in the onset of CVDs appears increasingly evident, as reflected by the impairment of proteins involved in lipid peroxidation, mitochondrial dynamics, respiratory chain complexes, and membrane polarization maintenance in CVD patients. Conversely, little is known about proteins responsible for the cross-talk between mitochondria and cytoplasm in cardiomyocytes. Mitochondrial transporters of the SLC25A family, in particular, are responsible for the translocation of nucleotides (e.g., ATP), amino acids (e.g., aspartate, glutamate, ornithine), organic acids (e.g. malate and 2-oxoglutarate), and other cofactors (e.g., inorganic phosphate, NAD+, FAD, carnitine, CoA derivatives) between the mitochondrial and cytosolic compartments. Thus, mitochondrial transporters play a key role in the mitochondria-cytosol cross-talk by leading metabolic pathways such as the malate/aspartate shuttle, the carnitine shuttle, the ATP export from mitochondria, and the regulation of permeability transition pore opening. Since all these pathways are crucial for maintaining healthy cardiomyocytes, mitochondrial carriers emerge as an interesting class of new possible pharmacological targets for CVD treatments.
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Doenças Cardiovasculares , Hipertensão , Traumatismo por Reperfusão , Humanos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Malatos/metabolismo , Ácido Aspártico/metabolismo , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Hipertensão/metabolismo , Proteínas Mitocondriais/metabolismo , Traumatismo por Reperfusão/metabolismo , Trifosfato de Adenosina/metabolismoRESUMO
BACKGROUND AND AIM: Supracondylar humeral fractures are the most common skeletal injury of childhood elbow. Treatment option for Gartland type II-III-IV fractures is based on closed reduction and percutaneous pinning (CRPP) fixation using Kirshner wires. Seldom open reduction is needed. Literature described different method of CRPP. The aim of the study is to report our experience in the surgical management of supracondylar humeral fractures comparing it with the literature, in order to identify useful information for a correct and better approach to reduce complications and improve clinical outcomes. METHODS: 148 patients with a mean age of 5.72 ± 2.52 years and with Gartland type II-III-IV humeral supracondylar fractures were treated with CRPP at our Orthopedic Pediatric Unit. They were divided into three groups according to surgical technique. Group A was represented by patients treated with cross pinning (1 medial and 1 lateral pin), Group B represented by 2 lateral pins while Group C represented by 2 lateral and one medial pin. Evaluation criteria are based on Mayo Elbow Performance Index (MEPI); Bauman's and Carrying Angle and Flynn's criteria. Data were recorded at the following times: T0 (before surgical procedure); T1 (one-month post-surgery); T2 (six months post-surgery). RESULTS: The three surgical techniques showed comparable results according to MEPI, Bauman's angle, Carrying's angle and Flynn's criteria from T0 to T1. There is an improvement for all Groups. Group C reported the best MEPI outcome at T2. However, 2 patients in this group did not show excellent results according to Flynn's criteria. CONCLUSIONS: There is no single and superior treatment for displaced humeral supracondylar fractures and that each fracture has its own personality.
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Angiomatoid fibrous histiocytoma (AFH) is a rare neoplasm described for the first time by Enzinger in 1979, and classified by World Health Organization 2020 as intermediate malignant potential neoplasm. It mostly occurs in the subcutis and is characterized by varying proportions of epithelioid, ovoid and spindle cells in a nodular and syncytial growth pattern, with some hemorrhagic pseudovascular spaces. In this paper, we report the clinical case of a 62-year-old man who presented with AFH on the right arm, and relapsed three years after first surgical excision. After a further three years, the patient presented with an intramuscular localization of AFH, and 12 months after this, a pulmonary metastasis of AFH was diagnosed. Given the rarity of the spreading of AFH, we performed Fluorescence In Situ Hybridization (FISH) and we detected EWSR1::CREB1 gene fusion.
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The aim of study was to evaluate the efficacy of blood loss prevention with Tranexamic acid in patients undergoing total knee arthroplasty (TKA). The Authors defined a new protocol that foresees the use of Tranexamic acid both pre-intra and post-operatively. Seventy patients indicated for TKA were enrolled. Thirty-five patients (control group) followed standard protocol without Tranexamic acid and the other 35 patients (study group) followed standard protocol with Tranexamic acid. We analyzed the values of hemoglobin (Hb), hematocrit (HCT) and red blood cells (RBCs) both pre-operatively (T0) and post-operatively: immediately after surgery (T1), at one day (T2) and three days post-op (T3). We observed statistical differences at T0 and T3 regarding the Hb, HT and RBCs value between the two groups. Moreover, 11.4% in the study and 28.5% in the control group required blood transfusion. No thrombotic or thrombo-embolic events were reported. We conclude that Tranexamic acid use, as in our protocol, reduces postoperative bleeding in primary knee arthroplasty, with the absence of thrombo-embolic events.
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Background: During the COVID-19 emergency, the incidence of fragility fractures in elderly patients remained unchanged. The management of these patients requires a multidisciplinary approach. The study aimed to assess the best surgical approach to treat COVID-19 patients with femoral neck fracture undergoing hemiarthroplasty (HA), comparing direct lateral (DL) versus direct anterior approach (DAA). Methods: A single-center, observational retrospective study including 50 patients affected by COVID-19 infection (30 males, 20 females) who underwent HA between April 2020 to April 2021 was performed. The patients were allocated into two groups according to the surgical approach used: lateral approach and anterior approach. For each patient, the data were recorded: age, sex, BMI, comorbidity, oxygen saturation (SpO2), fraction of the inspired oxygen (FiO2), type of ventilation invasive or non-invasive, HHb, P/F ratio (PaO2/FiO2), hemoglobin level the day of surgery and 1 day post operative, surgical time, Nottingham Hip Fractures Score (NHFS) and American Society of Anesthesiologists Score (ASA). The patients were observed from one hour before surgery until 48 h post-surgery of follow-up. The patients were stratified into five groups according to Alhazzani scores. A non-COVID-19 group of patients, as the control, was finally introduced. Results: A lateral position led to a better level of oxygenation (p < 0.01), compared to the supine anterior approach. We observed a better post-operative P/F ratio and a reduced need for invasive ventilation in patients lying in the lateral position. A statistically significant reduction in the surgical time emerged in patients treated with DAA (p < 0.01). Patients within the DAA group had a significantly lower blood loss compared to direct lateral approach. Conclusions: DL approach with lateral decubitus seems to preserved respiratory function in HA surgery. Thus, the lateral position may be associated with beneficial effects on gas exchange.
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Calcaneal fractures are a challenging clinical problem. Management of this type of injury remains controversial, especially in the context of intra-articular fractures. Surgical treatment with open reduction and internal synthesis (ORIF) is considered the standard treatment for CF, but it is associated with many complications. Several minimally invasive techniques such as balloon-assisted reduction, pin fixation, and tricalcium phosphate augmentation have been proposed to avoid the frequent and recurrent postoperative problems related to these fractures. We retrospectively examined 20 patients (mean age was 54.5), all undergoing minimally invasive calcaneoplasty surgery at our Department of Orthopaedics and Traumatology between 2012 and 2016. X-ray and CT scan were performed preoperatively and at 5 years of follow-up (57.9 ± 6 months). The American Orthopaedic Foot and Ankle Society (AOFAS) score was used for clinical examination, and the Short-Form (36) Health Survey (SF-36) score and Visual Analogue Scale (VAS) were used to assess the Health-Related Quality of Life (HRQoL). All 20 patients were available at the final follow-up. The mean AOFAS score was 82.25/100. The VAS results attest an overall average of 2.7/10 (0-9). The average of the parameters "Physical Health" and "Mental Health" was, respectively, 81.25 and 83.55. In terms of postoperative complications, we observed no cases of superficial or deep infections. Clinical response after balloon-assisted reduction, pin fixation, and tricalcium phosphate augmentation has shown a comparable or better outcome according to the AOFAS and VAS score. Quality-of-life scores, obtained according to the SF-36 questionnaire, are considered high. From both a clinical and quality-of-life point of view, our study highlights that there is not gender distinction. Further comparative studies with a higher number of patients are needed which assess the quality of life in the various techniques used to treat calcaneal fractures.
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Caseinolytic protease P (ClpP) is a mitochondrial serine protease. In mammalian cells, the heterodimerization of ClpP and its AAA+ ClpX chaperone results in a complex called ClpXP, which has a relevant role in protein homeostasis and in maintaining mitochondrial functionality through the degradation of mitochondrial misfolded or damaged proteins. Recent studies demonstrate that ClpP is upregulated in primary and metastatic human tumors, supports tumor cell proliferation, and its overexpression desensitizes cells to cisplatin. Interestingly, small modulators of ClpP activity, both activators and inhibitors, are able to impair oxidative phosphorylation in cancer cells and to induce apoptosis. This review provides an overview of the role of ClpP in regulating mitochondrial functionality, in supporting tumor cell proliferation and cisplatin resistance; finally, we discuss whether this protease could represent a new prognostic marker and therapeutic target for the treatment of cancer.
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Biomarcadores Tumorais/metabolismo , Endopeptidase Clp/metabolismo , Mitocôndrias/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Animais , Apoptose/genética , Biomarcadores Tumorais/genética , Proliferação de Células/genética , Endopeptidase Clp/genética , Humanos , Mitocôndrias/genética , Mitocôndrias/patologia , Metástase Neoplásica , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/patologiaRESUMO
ADP/ATP carriers (AACs) are mitochondrial transport proteins playing a strategic role in maintaining the respiratory chain activity, fueling the cell with ATP, and also regulating mitochondrial apoptosis. To understand if AACs might represent a new molecular target for cancer treatment, we evaluated AAC expression levels in cancer/normal tissue pairs available on the Tissue Cancer Genome Atlas database (TCGA), observing that AACs are dysregulated in most of the available samples. It was observed that at least two AACs showed a significant differential expression in all the available kidney cancer/normal tissue pairs. Thus, we investigated AAC expression in the corresponding kidney non-cancer (HK2)/cancer (RCC-Shaw and CaKi-1) cell lines, grown in complete medium or serum starvation, for investigating how metabolic alteration induced by different growth conditions might influence AAC expression and resistance to mitochondrial apoptosis initiators, such as "staurosporine" or the AAC highly selective inhibitor "carboxyatractyloside". Our analyses showed that AAC2 and AAC3 transcripts are more expressed than AAC1 in all the investigated kidney cell lines grown in complete medium, whereas serum starvation causes an increase of at least two AAC transcripts in kidney cancer cell lines compared to non-cancer cells. However, the total AAC protein content is decreased in the investigated cancer cell lines, above all in the serum-free medium. The observed decrease in AAC protein content might be responsible for the decrease of OXPHOS activity and for the observed lowered sensitivity to mitochondrial apoptosis induced by staurosporine or carboxyatractyloside. Notably, the cumulative probability of the survival of kidney cancer patients seriously decreases with the decrease of AAC1 expression in KIRC and KIRP tissues making AAC1 a possible new biomarker of metabolic remodeling and survival in kidney cancers.
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Translocador 2 do Nucleotídeo Adenina/genética , Translocador 3 do Nucleotídeo Adenina/genética , Arilamina N-Acetiltransferase/genética , Isoenzimas/genética , Neoplasias Renais/genética , Translocases Mitocondriais de ADP e ATP/genética , Sequência de Aminoácidos/genética , Apoptose/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Rim/metabolismo , Rim/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Translocases Mitocondriais de ADP e ATP/metabolismo , Fosforilação OxidativaRESUMO
Type I endometrial cancer (EC) is the most common form of EC, displaying less aggressive behavior than type II. The development of type I endometrial cancer is considered a multistep process, with slow progression from normal endometrium to hyperplasia, the premalignant form, and endometrial cancer as a result of an unopposed estrogenic stimulation. The role of mitochondria in type I EC tumor progression and prognosis is currently emerging. This review aims to explore mitochondrial alterations in this cancer and in endometrial hyperplasia focusing on mitochondrial DNA mutations, respiratory complex I deficiency, and the activation of mitochondrial quality control systems. A deeper understanding of altered mitochondrial pathways in type I EC could provide novel opportunities to discover new diagnostic and prognostic markers as well as potential therapeutic targets.
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DNA Mitocondrial/genética , Neoplasias do Endométrio/genética , Mitocôndrias/genética , Mutação , Lesões Pré-Cancerosas/genética , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Mitocôndrias/metabolismo , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Lesões Pré-Cancerosas/metabolismo , PrognósticoRESUMO
Intravascular papillary endothelial hyperplasia is a rare benign vascular lesion of the skin and subcutaneous tissues, characterized by a reactive proliferation of endothelial cells that can present de novo in normal blood vessels (primary intravascular papillary endothelial hyperplasia), but it can also develop from a pre-existing vascular process (type II intravascular papillary endothelial hyperplasia), or it can arise in an extravascular location from a post-traumatic haematoma. The differential diagnosis between intravascular papillary endothelial hyperplasia and malignant vascular tumours can be challenging, due to the lacking of a specific radiologic description. We present a case of intravascular papillary endothelial hyperplasia of the hand radiologically mimicking a hemangiopericytoma.
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Mitochondrial structural and functional integrity is maintained through the coordination of several processes (e.g., biogenesis, dynamics, mitophagy), collectively referred to as mitochondrial quality control (MQC). Dysfunctional MQC and inflammation are hallmarks of aging and are involved in the pathogenesis of muscle wasting disorders, including sarcopenia and cachexia. One of the consequences of failing MQC is the release of mitochondria-derived damage-associated molecular patterns (DAMPs). By virtue of their bacterial ancestry, these molecules can trigger an inflammatory response by interacting with receptors similar to those involved in pathogen-associated responses. Mitochondria-derived DAMPs, especially cell-free mitochondrial DNA, have recently been associated with conditions characterized by chronic inflammation, such as aging and degenerative diseases. Yet, their actual implication in the aging process and muscle wasting disorders is at an early stage of investigation. Here, we review the contribution of mitochondria-derived DAMPs to age-related systemic inflammation. We also provide arguments in support of the exploitation of such signaling pathways for the management of muscle wasting conditions.
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Envelhecimento/patologia , DNA Mitocondrial/sangue , Inflamação/sangue , Inflamação/patologia , Mitocôndrias/patologia , Sarcopenia/sangue , Sarcopenia/patologia , Animais , Humanos , Estresse OxidativoRESUMO
Chemotherapy can cause cachexia, which consists of weight loss associated with muscle atrophy. The exact mechanisms underlying this skeletal muscle toxicity are largely unknown and co-therapies to attenuate chemotherapy-induced side effects are lacking. By using a rat model of cisplatin-induced cachexia, we here characterized the mitochondrial homeostasis in tibialis anterior cachectic muscle and evaluated the potential beneficial effects of the growth hormone secretagogues (GHS) hexarelin and JMV2894 in this setting. We found that cisplatin treatment caused a decrease in mitochondrial biogenesis (PGC-1α, NRF-1, TFAM, mtDNA, ND1), mitochondrial mass (Porin and Citrate synthase activity) and fusion index (MFN2, Drp1), together with changes in the expression of autophagy-related genes (AKT/FoxO pathway, Atg1, Beclin1, LC3AII, p62) and enhanced ROS production (PRX III, MnSOD). Importantly, JMV2894 and hexarelin are capable to antagonize this chemotherapy-induced mitochondrial dysfunction. Thus, our findings reveal a key-role played by mitochondria in the mechanism responsible for GHS beneficial effects in skeletal muscle, strongly indicating that targeting mitochondrial dysfunction might be a promising area of research in developing therapeutic strategies to prevent or limit muscle wasting in cachexia.
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Caquexia/induzido quimicamente , Cisplatino/efeitos adversos , Hormônio do Crescimento/farmacologia , Indóis/farmacologia , Mitocôndrias/patologia , Músculo Esquelético/metabolismo , Oligopeptídeos/farmacologia , Piperidinas/farmacologia , Secretagogos/farmacologia , Triazóis/farmacologia , Animais , Autofagia/efeitos dos fármacos , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Caquexia/patologia , Modelos Animais de Doenças , Proteína Forkhead Box O3/metabolismo , Hormônio do Crescimento/administração & dosagem , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Biogênese de Organelas , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Secretagogos/administração & dosagemRESUMO
OBJECTIVES: Tenosynovial chondromatosis is an uncommon type of chondro-dysplasia of synovial and connective tissue. We report a case of a patient with a primary right wrist extra-articular chondromatosis extending to the flexor and the extensor compartments. METHODS: Until now, there has been no study describing double surgical access for such a case. RESULTS: Due to the extension, two surgical accesses are required to completely remove the neoformation. CONCLUSIONS: At 2 years of follow-up, the good functional-clinical results and absence of recurrence confirm the validity of our surgical strategy.
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Bladder cancer (BC) is a major cause of mortality worldwide as it currently lacks fully reliable markers of disease outcome and effective molecular targets for therapy. Mitochondria play a key role in cell metabolism but the role of mitochondrial dysfunctions in BC has been scarcely investigated. In this review, we explored current evidence for the potential role of mitochondrial DNA (mtDNA) alterations (point mutations and copy number) as disease markers in BC. Some germline mtDNA mutations detectable in blood could represent a non-invasive tool to predict the risk of developing BC. MtDNA copy number and tumor specific mtDNA mutations and RNAs showed encouraging results as novel molecular markers for early detection of BC in body fluids. Moreover, mitochondrial proteins Lon protease, Mitofusin-2, and TFAM may have prognostic/predictive value and may represent potential therapeutic targets. A deeper understanding of mitochondrial dysfunctions in BC could therefore provide novel opportunities for targeted therapeutic strategies.
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Biomarcadores/metabolismo , DNA Mitocondrial/genética , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Neoplasias da Bexiga Urinária/complicações , Animais , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Prognóstico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
We previously reported the ability of dietary supplementation with acetyl-l-carnitine (ALCAR) to prevent age-related decreases of mitochondrial biogenesis in skeletal muscle and liver of old rats. Here, we investigate the effects of ALCAR supplementation in cerebral hemispheres and cerebellum of old rats by analyzing several parameters linked to mitochondrial biogenesis, mitochondrial dynamics and antioxidant defenses. We measured the level of the coactivators PGC-1α and PGC-1ß and of the factors regulating mitochondrial biogenesis, finding an age-related decrease of PGC-1ß, whereas PGC-1α level was unvaried. Twenty eight-month old rats supplemented with ALCAR for one and two months showed increased levels of both factors. Accordingly, the expression of the two transcription factors NRF-1 and TFAM followed the same trend of PGC-1ß. The level of mtDNA, ND1 and the activity of citrate synthase, were decreased with aging and increased following ALCAR treatment. Furthermore, ALCAR counteracted the age-related increase of deleted mtDNA. We also analyzed the content of proteins involved in mitochondrial dynamics (Drp1, Fis1, OPA1 and MNF2) and found an age-dependent increase of MFN2 and of the long form of OPA1. ALCAR treatment restored the content of the two proteins to the level of the young rats. No changes with aging and ALCAR were observed for Drp1 and Fis1. ALCAR reduced total cellular levels of oxidized PRXs and counteracted the age-related decrease of PRX3 and SOD2. Overall, our findings indicate a systemic positive effect of ALCAR dietary treatment and a tissue specific regulation of mitochondrial homeostasis in brain of old rats. Moreover, it appears that ALCAR acts as a nutrient since in most cases its effects were almost completely abolished one month after treatment suspension. Dietary supplementation of old rats with this compound seems a valuable approach to prevent age-related mitochondrial dysfunction and might ultimately represent a strategy to delay age-associated negative consequences in mitochondrial homeostasis.
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Acetilcarnitina/farmacologia , Envelhecimento/metabolismo , Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Suplementos Nutricionais , Mitocôndrias/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Biogênese de Organelas , Fatores Etários , Envelhecimento/genética , Envelhecimento/patologia , Animais , Encéfalo/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas Mitocondriais/metabolismo , Mutação , Estresse Oxidativo/efeitos dos fármacos , Ratos Endogâmicos F344 , Fatores de Transcrição/metabolismoRESUMO
Pathogenic mtDNA mutations associated with alterations of respiratory complex I, mitochondrial proliferation (oncocytic-like phenotype) and increase in antioxidant response were previously reported in type I endometrial carcinoma (EC). To evaluate whether in the presence of pathogenic mtDNA mutations other mitochondrial adaptive processes are triggered by cancer cells, the expression level of proteins involved in mitochondrial dynamics, mitophagy, proteolysis and apoptosis were evaluated in type I ECs harboring pathogenic mtDNA mutations and complex I deficiency. An increase in the fission protein Drp1, in the mitophagy protein BNIP3, in the mitochondrial protease CLPP, in the antioxidant and anti-apoptotic protein ALR and in Bcl-2 as well as a decrease in the fusion protein Mfn2 were found in cancer compared to matched non malignant tissue. Moreover, the level of these proteins was measured in type I EC, in hyperplastic (the premalignant form) and in non malignant tissues to verify whether the altered expression of these proteins is a common feature of endometrial cancer and of hyperplastic tissue. This analysis confirmed in type I EC samples, but not in hyperplasia, an alteration of the expression level of these proteins. These results suggest that in this cancer mitochondrial fission, antioxidant and anti-apoptotic response may be activated, as well as the discharge of damaged mitochondrial proteins as adaptation processes to mitochondrial dysfunction.
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Complexo I de Transporte de Elétrons/deficiência , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Mitocôndrias/metabolismo , Mitofagia , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/metabolismo , Complexo I de Transporte de Elétrons/genética , Feminino , Humanos , Proteínas Mitocondriais , Proteínas de Neoplasias , Proteólise , Células Tumorais CultivadasRESUMO
The aim of the virgin olive oil extraction process is mainly to obtain the best quality oil from fruits, by only applying mechanical actions while guaranteeing the highest overall efficiency. Currently, the mechanical methods used to extract virgin oils from olives are basically of two types: the discontinuous system (obsolete) and the continuous one. Anyway the system defined as "continuous" is composed of several steps which are not all completely continuous, due to the presence of the malaxer, a device that works in batch. The aim of the paper was to design, realize and test the first full scale sono-exchanger for the virgin olive oil industry, to be placed immediately after the crusher and before the malaxer. The innovative device is mainly composed of a triple concentric pipe heat exchanger combined with three ultrasound probes. This mechanical solution allows both the cell walls (which release the oil droplets) along with the minor compounds to be destroyed more effectively and the heat exchange between the olive paste and the process water to be accelerated. This strategy represents the first step towards the transformation of the malaxing step from a batch operation into a real continuous process, thus improving the working capacity of the industrial plants. Considering the heterogeneity of the olive paste, which is composed of different tissues, the design of the sono-exchanger required a thorough fluid dynamic analysis. The thermal effects of the sono-exchanger were monitored by measuring the temperature of the product at the inlet and the outlet of the device; in addition, the measurement of the pigments concentration in the product allowed monitoring the mechanical effects of the sono-exchanger. The effects of the innovative process were also evaluated in terms of extra virgin olive oil yields and quality, evaluating the main legal parameters, the polyphenol and tocopherol content. Moreover, the activity of the polyphenol oxidase enzyme in the olive paste was measured.
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Fracionamento Químico/instrumentação , Modelos Teóricos , Azeite de Oliva/isolamento & purificação , Ondas Ultrassônicas , Engenharia , Desenho de Equipamento , Qualidade dos Alimentos , HidrodinâmicaRESUMO
Three different flavoring methods of olive oil were tested employing two different herbs, thyme and oregano. The traditional method consist in the infusion of herbs into the oil. A second scarcely diffused method is based on the addition of herbs to the crushed olives before the malaxation step during the extraction process. The third innovative method is the implementation of the ultrasound before the olive paste malaxation. The objective of the study is to verify the effect of the treatments on the quality of the product, assessed by means of the chemical characteristics, the phenol composition and the radical scavenging activity of the resulting oils. The less favorable method was the addition of herbs directly to the oil. A positive effect was achieved by the addition of herbs to the olive paste and other advantages were attained by the employment of ultrasound. These last two methods allow to produce oils "ready to sell", instead the infused oils need to be filtered. Moreover, the flavoring methods applied during the extraction process determine a significant increment of phenolic content and radical scavenging activity of olive oils. The increments were higher when oregano is used instead of thyme. Ultrasound inhibited the olive polyphenoloxidase, the endogenous enzyme responsible for olive oil phenol oxidation. This treatment of olive paste mixed with herbs before malaxation was revealed as the most favorable method due to the best efficiency, reduced time consumption and minor labor, enhancing the product quality of flavored olive oil.