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BACKGROUND: Currently there are not enough studies that compared frequent types of collective sports with regard to the prevalence of pain and disability of the lower limb. OBJECTIVE: To determine the prevalence of lower limb pain and disability in team sports players. METHODS: 388 athletes with average age 27.26 ± 4.69, from sports clubs at the national level were included in the study. The Oxford Hip Score was used to determine the prevalence of hip pain. The International Knee Documentation Committee was used to determine the prevalence of knee pain. The Foot and Ankle Disability Index was used to determine the prevalence of ankle pain. RESULTS: Hockey players had a prevalence of hip pain of 97.2% and a 14.3 times higher risk of developing hip pain compared with football and floorball players. Floorball players had a 81.9% prevalence of knee pain, with a 3.8 times higher the risk of knee pain compared with football and hockey. Floorball players had a 62.3% prevalence of ankle pain and a 1.8 times higher the risk of developing ankle pain compared with football and hockey players. CONCLUSIONS: The highest percentage of knee 81.9% and ankle 62.3% pain, as well as the greatest risk of pain, was found among floorball players. Hockey players had the highest prevalence (97.2%) and risk of developing hip pain.
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Artralgia , Hóquei , Futebol , Adulto , Humanos , Adulto Jovem , Artralgia/epidemiologia , Extremidade Inferior , PrevalênciaRESUMO
Spisulosine (1-deoxysphinganine) is a sphingoid amino alcohol isolated from the sea clams that showed potent antiproliferative activity against a broad spectrum of solid tumors but failed in clinical trials due to neurotoxicity. However, its structural similarity to other bioactive sphingoids, interesting mode of action, and appreciable potency against cancer cells make it a suitable lead for future anticancer drug development. The present study was conducted to elucidate mechanisms of the antiproliferative/cytotoxic effects of newly synthesized spisulosine analog homospisulosine (KP7). The evaluation was performed on cervical carcinoma cells, representing an in vitro model of one of the most common cancer types and a significant worldwide cause of women's cancer mortality. Treatment with homospisulosine (2.0 µM) for 24, 48, and 72 h significantly inhibited the growth of HeLa cells in vitro and induced apoptosis detectable by DNA fragmentation, externalization of phosphatidylserine, dissipation of mitochondrial membrane potential, activation of caspase-3 and cleavage of PARP. In addition, treating HeLa cells with spisulosine increased p27 and Bcl-2 on protein levels and phosphorylation of Bcl-2 on Ser70 residue. These results support the potential for spisulosine analogs represented here by homospisulosine for future therapeutic development.
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Antineoplásicos , Carcinoma , Feminino , Humanos , Células HeLa , Regulação para Cima , Fosforilação , Apoptose , Antineoplásicos/farmacologiaRESUMO
Derivatives combining acridine, pyrrole, and thiazolidine rings have emerged as promising candidates in the field of antitumor drug discovery. This paper aims to highlight the importance of these three structural motifs in developing potent and selective anticancer agents. The integration of these rings within a single molecule offers the potential for synergistic effects, targeting multiple pathways involved in tumor growth and progression. Spiro derivatives were efficiently synthesized in a two-step process starting from isothiocyanates and 2-cyanoacetohydrazide. The thiourea side chain in spiro derivatives was utilized as a key component for the construction of the thiazolidine-4-one ring through regioselective reactions with bifunctional reagents, namely methyl-bromoacetate, dietyl-acetylenedicarboxylate, ethyl-2-bromopropionate, and ethyl-2-bromovalerate. These reactions resulted in the formation of a single regioisomeric product for each derivative. Advanced spectroscopic techniques, including 1D and 2D NMR, FT-IR, HRMS, and single-crystal analysis, were employed to meticulously characterize the chemical structures of the synthesized derivatives. Furthermore, the influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC50 values determined via MTT assays. Notably, derivatives containing ester functional groups exhibited exceptional activity against all tested cancer cell lines, boasting IC50 values below 10 µM. Particularly striking were the spiro derivatives with methoxy groups at position 3 and nitro groups at position 4 of the phenyl ring. These compounds displayed remarkable selectivity and exhibited heightened activity against HCT-116 and Jurkat cell lines. Additionally, 4-oxo-1,3-thiazolidin-2-ylidene derivatives demonstrated a significant activity against MCF-7 and HCT-116 cancer cell lines.
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Acridinas , Antineoplásicos , Humanos , Pirróis/farmacologia , Tiazolidinas/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Antineoplásicos/farmacologia , Células HCT116RESUMO
BACKGROUND Low back pain (LBP) is a common concern among professional athletes, potentially hindering performance and career longevity. However, comparative assessments of LBP prevalence and severity across various sports remain scarce. This study aimed to evaluate the factors associated with LBP in 388 professional athletes, including football, ice hockey, and floorball players. MATERIAL AND METHODS Conducted from June 2021 to September 2022, this cross-sectional study incorporated 388 athletes from national elite clubs, including football (n=148), ice hockey (n=179), and floorball (n=61). The Oswestry Disability Index (ODI), comprising sections like pain intensity, self-care, lifting, walking, sitting, standing, sleeping, sexual life, social life, and traveling, was employed to evaluate spinal pain and disability. RESULTS The study found no significant disparities in the LBP assessment among the groups. The relative risk (OR) of LBP and disability varied among the sports: football players displayed a lower risk (OR=0.49; 95% CI 0.32-0.74, P≤0.001), while ice hockey players had a higher risk (OR=2.18; 95% CI 1.45-3.29, P≤0.001) compared to the others. In contrast, the risk for floorball players (OR=0.82; 95% CI 0.47-1.41) did not significantly deviate from that of the other two sports. CONCLUSIONS LBP prevalence stood at 42.6% for football players, 60.1% for ice hockey players, and 49.2% for floorball players. Among these, ice hockey players exhibited a 2.18-fold increased risk of developing LBP and associated disability when compared to their football and floorball counterparts.
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Futebol Americano , Hóquei , Dor Lombar , Humanos , Estudos Transversais , Atletas , Medição de RiscoRESUMO
BACKGROUND: The minimum clinically important difference (MCID) for the St George's Respiratory Questionnaire (SGRQ) is debated in chronic obstructive pulmonary disease (COPD) quality-of-life (QoL) assessments. This study aimed to determine whether there is a difference in predictors of clinically significant improvement between the traditional (value of 4) and newly proposed MCID SGRQ (value of 7) after climatic rehabilitation treatment. Climatic rehabilitation treatment consists of two main parts: climatotherapy, which typically involves the controlled exposure of individuals to natural environmental elements, and climatic rehabilitation, which includes other therapeutic factors such as physical activities as well as educating the patient to change their lifestyle. METHODS: This study included 90 consecutive patients diagnosed with COPD who underwent structured complex pulmonary rehabilitation in High Tatras, part of the Carpathian Mountains. The examination before and after treatment included spirometry, QoL assessment using the SGRQ, 6 min walk test (6-MWT), and the Borg, Beck and Zung scale. RESULTS: Patients showed statistically significant improvement after the intervention in FEV1, FEV1/FVC, 6-MWT, (p < 0.001), anxiety scores, depression, and improvement in dyspnoea both before and after the 6-MWT (p < 0.001). For both MCID for SGRQ levels 4 and 7, we confirmed the same predictors of clinical improvement for bronchial obstruction grade (spirometry) and exercise capacity (6-MWT), for quality of life in activity score and total score. CONCLUSION: The results suggest that both the proposed MCID for SGRQ values could be sufficient to assess the clinical significance of the achieved change in health status when assessing the need for pulmonary rehabilitation comprising climatotherapy in patients with COPD.
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Tsetse flies are the cyclical vectors of African trypanosomes and one of several methods to manage this vector is the sterile insect technique (SIT). The ability to determine the sex of tsetse pupae with the objective to separate the sexes before adult emergence has been a major goal for decades for tsetse management programmes with an SIT component. Tsetse females develop faster and pharate females inside the pupae melanise 1-2 days before males. This earlier melanisation can be detected by infrared cameras through the pupal shell, and the newly developed Near InfraRed Pupae Sex Sorter (NIRPSS) takes advantage of this. The melanisation process is not homogeneous for all fly organs and the pupa needs to be examined ventrally, dorsally and laterally to ensure accurate classification by an image analysis algorithm. When the pupae are maturing at a constant temperature of 24 °C and sorted at the appropriate age, 24 days post-larviposition for Glossina palpalis gambiensis, the sorting machine can efficiently separate the sexes. The recovered male pupae can then be sterilised for field releases of males, while the rest of the pupae can be used to maintain the laboratory colony. The sorting process with the new NIRPSS had no negative impact on adult emergence and flight ability. A mean male recovery of 62.82 ± 3.61% was enough to provide sterile males to an operational SIT programme, while mean contamination with females (4.69 ± 3.02%) was low enough to have no impact on the maintenance of a laboratory colony.
Title: Imagerie dans l'infrarouge proche pour le tri automatisé du sexe des pupes de glossines comme aide à la technique de l'insecte stérile. Abstract: Les glossines sont les vecteurs cycliques des trypanosomes africains et la technique de l'insecte stérile (TIS) est l'une des méthodes de gestion de ce vecteur. La capacité à déterminer le sexe des pupes de glossines dans le but de séparer les sexes avant l'émergence des adultes a été un objectif majeur, pendant des décennies, pour les programmes de lutte contre les glossines avec une composante TIS. Les femelles tsé-tsé se développent plus rapidement et les pharates femelles à l'intérieur des pupes se mélanisent 1 à 2 jours avant les mâles. Cette mélanisation précoce peut être détectée par des caméras infrarouges à travers la coque de la pupe, ce que le nouveau trieur de sexe des pupes dans le proche infrarouge (TSPPIR) utilise. Le processus de mélanisation n'est pas homogène pour tous les organes de la mouche et la pupe doit être examinée ventralement, dorsalement et latéralement pour assurer une classification précise par un algorithme d'analyse d'image. Lorsque les pupes mûrissent à une température constante de 24 °C et sont triées à l'âge approprié, 24 jours après la larviposition pour Glossina palpalis gambiensis, la machine de tri peut séparer efficacement les sexes. Les pupes mâles récupérées peuvent ensuite être stérilisées pour les lâchers de mâles sur le terrain tandis que le reste des pupes peut être utilisé pour maintenir la colonie de laboratoire. Le processus de tri avec le nouveau TSPPIR n'a eu aucun impact négatif sur l'émergence et la capacité de vol des adultes. Une récupération moyenne des mâles de 62,82 ± 3,61% était suffisante pour fournir des mâles stériles à un programme TIS opérationnel, tandis que la contamination moyenne par les femelles (4,69 ± 3,02%) était suffisamment faible pour n'avoir aucun impact sur le maintien d'une colonie de laboratoire.
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Infertilidade Masculina , Trypanosoma , Moscas Tsé-Tsé , Humanos , Animais , Feminino , Masculino , Pupa , TemperaturaRESUMO
Cancer is a fatal disease with a complex pathophysiology. Lack of specificity and cytotoxicity, as well as the multidrug resistance of traditional cancer chemotherapy, are the most common limitations that often cause treatment failure. Thus, in recent years, significant efforts have concentrated on the development of a modernistic field called nano-oncology, which provides the possibility of using nanoparticles (NPs) with the aim to detect, target, and treat cancer diseases. In comparison with conventional anticancer strategies, NPs provide a targeted approach, preventing undesirable side effects. What is more, nanoparticle-based drug delivery systems have shown good pharmacokinetics and precise targeting, as well as reduced multidrug resistance. It has been documented that, in cancer cells, NPs promote reactive oxygen species (ROS) production, induce cell cycle arrest and apoptosis, activate ER (endoplasmic reticulum) stress, modulate various signaling pathways, etc. Furthermore, their ability to inhibit tumor growth in vivo has also been documented. In this paper, we have reviewed the role of silver NPs (AgNPs) in cancer nanomedicine, discussing numerous mechanisms by which they render anticancer properties under both in vitro and in vivo conditions, as well as their potential in the diagnosis of cancer.
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Approximately 20% of sleeping sickness patients exhibit respiratory complications, however, with a largely unknown role of the parasite. Here we show that tsetse fly-transmitted Trypanosoma brucei parasites rapidly and permanently colonize the lungs and occupy the extravascular spaces surrounding the blood vessels of the alveoli and bronchi. They are present as nests of multiplying parasites exhibiting close interactions with collagen and active secretion of extracellular vesicles. The local immune response shows a substantial increase of monocytes, macrophages, dendritic cells and γδ and activated αß T cells and a later influx of neutrophils. Interestingly, parasite presence results in a significant reduction of B cells, eosinophils and natural killer cells. T. brucei infected mice show no infection-associated pulmonary dysfunction, mirroring the limited pulmonary clinical complications during sleeping sickness. However, the substantial reduction of the various immune cells may render individuals more susceptible to opportunistic infections, as evident by a co-infection experiment with respiratory syncytial virus. Collectively, these observations provide insights into a largely overlooked target organ, and may trigger new diagnostic and supportive therapeutic approaches for sleeping sickness.
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Trypanosoma brucei brucei , Tripanossomíase Africana , Moscas Tsé-Tsé , Camundongos , Animais , Tripanossomíase Africana/parasitologia , Moscas Tsé-Tsé/parasitologia , Tórax , Alvéolos PulmonaresRESUMO
Metallodrugs form a large family of therapeutic agents against cancer, among which is cisplatin, a paradigmatic member. Therapeutic resistance and undesired side effects to Pt(II) related drugs, prompts research on different metal-ligand combinations with potentially enhanced biological activity. We present the synthesis and biological tests of novel palladium(II) complexes containing bisdemethoxycurcumin (BDMC) 1 and 2. Complexes were fully characterized and their structures were determined by X-ray diffraction. Their biological activity was assessed for several selected human tumor cell lines: Jurkat (human leukaemic T-cell lymphoma), HCT-116 (human colorectal carcinoma), HeLa (human cervix epitheloid carcinoma), MCF-7 (human breast adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), A549 (human alveolar adenocarcinoma), Caco-2 (human colorectal carcinoma), and for non-cancerous 3T3 cells (murine fibroblasts). The cytotoxicity of 1 is comparable to that of cisplatin, and superior to that of 2 in all cell lines. It is a correlation between IC50 values of 1 and 2 in the eight studied cell types, promising a potential use as anti-proliferative drugs. Moreover, for Jurkat cell line, complexes 1 and 2, show an enhanced activity. DFT and docking calculations on the NF-κB protein, Human Serum Albumin (HSA), and DNA were performed for 1 and 2 to correlate with their biological activities.
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Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação , Citotoxinas , DNA de Neoplasias , Diarileptanoides , Simulação de Acoplamento Molecular , Paládio , Células 3T3 , Animais , Células CACO-2 , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Citotoxinas/química , Citotoxinas/farmacologia , DNA de Neoplasias/química , DNA de Neoplasias/metabolismo , Diarileptanoides/química , Diarileptanoides/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Células HeLa , Humanos , Células Jurkat , Células MCF-7 , Camundongos , Paládio/química , Paládio/farmacologiaRESUMO
BACKGROUND/AIM: A series of experiments on HeLa cells were conducted to provide new information concerning the anti-cancer properties of jaspine B hydrochloride (JBH). MATERIALS AND METHODS: HeLa cells treated with 0.5 µmol/l JBH for 24, 48, and 72 h underwent flow cytometric analysis of the cell cycle, and measurement of phosphatidylserine externalization, mitochondrial membrane potential (MMP), casp-3 activation, cleavage of PARP, ceramide levels, aSMase activity, and Bcl-2 release. nSMase activity was measured by a colorimetric assay. Gene expression was determined by qRT-PCR. Immunocytochemistry was performed to detect p21 and p27 expression. RESULTS: JBH-induced apoptosis in HeLa cells associated with externalization of phosphatidylserine, reduced MMP, activation of casp-3, and cleavage of PARP as well as up-regulation of TNF-α, FasL, and casp-8. Significant increase in nSMase activity, ceramide levels, Bcl-2 release (predominantly in the inactive form), and pro-apoptotic nuclear localization of p21 and p27 were also detected. CONCLUSION: JBH-induced apoptosis in HeLa cells is associated with disrupted sphingolipid homeostasis resulting in increased ceramide levels.
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Apoptose/efeitos dos fármacos , Ceramidas/metabolismo , Esfingolipídeos/metabolismo , Esfingosina/análogos & derivados , Proliferação de Células/efeitos dos fármacos , Células HeLa , Humanos , Transdução de Sinais/efeitos dos fármacos , Esfingosina/farmacologiaRESUMO
Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature of this gene product and involvement in the activity of certain nucleoside analogues indicates that it represents a potential novel drug target.
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Cerebral palsy (CP) is a group of the most common developmental disorders affecting movement and posture of the body, causing activity limitations and participation restrictions. The motor disorders of persons with CP are often accompanied by disturbances of sensation, cognition, communication and perception. The symptoms of CP are very diverse and persons with CP are usually presented with a mixed type of symptoms. The non-progressive disturbances can be attributed to disorders that were developed during pregnancy, birth and/or infant stage. The aim of this study was to improve physicians' professional practice of Physical and Rehabilitation Medicine for persons with cerebral palsy in order to improve their functionality, social and community integration, and to reduce activity limitations and/or participation restrictions. A systematic review of the literature including an 18-year period and consensus procedure by means of a Delphi process was performed and involved the delegates of all European countries represented in the Union of European Medical Specialists Physical and Rehabilitation Medicine (UEMS PRM) Section. As the result of a Consensus Delphi procedure, 74 recommendations are presented together with the systematic literature review. The PRM physician's role for persons with cerebral palsy is to lead and coordinate the multiprofessional team, working in an interdisciplinary way. They should propose and manage the complex but individual PRM program developed in conjunction with other health professionals, medical specialists and importantly in agreement with the patient, their family and care giver. This should be, according to the specific medical diagnosis to improve patients' health, functioning, social and education status, considering all impairments, comorbidities and complications, activity limitations and participation restrictions. This evidence-based position paper is representing the official position of The European Union through the UEMS PRM Section and designates the professional role of PRM physicians in persons with cerebral palsy.
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Paralisia Cerebral , Medicina Física e Reabilitação , Europa (Continente) , Humanos , Prática ProfissionalRESUMO
Tsetse flies (genus Glossina), the sole vectors of African trypanosomiasis, are distinct from most other insects, due to dramatic morphological and physiological adaptations required to support their unique biology. These adaptations are driven by demands associated with obligate hematophagy and viviparous reproduction. Obligate viviparity entails intrauterine larval development and the provision of maternal nutrients for the developing larvae. The reduced reproductive capacity/rate associated with this biology results in increased inter- and intra-sexual competition. Here, we use phase contrast microcomputed tomography (pcMicroCT) to analyze morphological adaptations associated with viviparous biology. These include (1) modifications facilitating abdominal distention required during blood feeding and pregnancy, (2) abdominal and uterine musculature adaptations for gestation and parturition of developed larvae, (3) reduced ovarian structure and capacity, (4) structural features of the male-derived spermatophore optimizing semen/sperm delivery and inhibition of insemination by competing males and (5) structural features of the milk gland facilitating nutrient incorporation and transfer into the uterus. Three-dimensional analysis of these features provides unprecedented opportunities for examination and discovery of internal morphological features not possible with traditional microscopy techniques and provides new opportunities for comparative morphological analyses over time and between species.
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BACKGROUND Lymphedema is a clinical manifestation of lymphatic system failure, caused by an imbalance between the transport capacity of the lymphatic system and the volume of the produced lymph. Lymphedema is complication and significantly worsens quality of life (QoL). MATERIAL AND METHODS There were 50 patients diagnosed with secondary lymphedema of the lower extremities after gynecological cancer followed by radiotherapy included in this study. The average age was 57.76 years (standard deviation±10.08). Patients were treated at the Department of Physiotherapy, Balneology and Medical Rehabilitation, in hospital NsP in Bardejov. During therapy, we applied manual lymphatic drainage, instrumental lymphatic drainage, multilayer bandage, vascular gymnastics (with loaded external compression), hydrotherapy, and patient education on the adjustment necessary for a life-long regimen. The circumference of the limb was measured using the Kuhnkes disk method, QoL was assessed using the LYMQOL LEG questionnaire, and for assessment of pain the Visual Analogue Scale (VAS) was used. RESULTS After treatment, we found a reduction in lymphedema (P<0.001), an increase in QoL (P<0.001), and a reduction in pain (P<0.001). We found a significant relationship between QoL change and pain in the domains of symptoms, function, and overall QoL (P<0.005). The results showed that reduction of lymphedema was not a significant predictor of QoL (P>0.001). CONCLUSIONS We found a positive effect in the treatment of secondary lymphedema of the lower extremity on the QoL of women after uterine cancer surgery, and also found that reduction of lymphedema and age were not predictors of improvement in QoL.
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Bandagens Compressivas , Neoplasias dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos em Ginecologia , Linfedema/terapia , Modalidades de Fisioterapia , Complicações Pós-Operatórias/terapia , Qualidade de Vida , Idoso , Feminino , Humanos , Hidroterapia/métodos , Linfedema/fisiopatologia , Drenagem Linfática Manual/métodos , Pessoa de Meia-Idade , Medição da Dor , Educação de Pacientes como Assunto/métodos , Complicações Pós-Operatórias/fisiopatologia , Resultado do TratamentoRESUMO
The ability of horse chestnut extract (HCE) to induce contraction force in fibroblasts, a process with remarkable significance in skin repair, motivated us to evaluate its wound healing potential in a series of experiments. In the in vitro study of the ability of human dermal fibroblasts to form myofibroblast-like cells was evaluated at the protein level (Western blot and immunofluorescence). The in vivo study was conducted on male Sprague-Dawley rats with inflicted wounds (one open circular and one sutured incision) on their backs. Rats were topically treated with two tested HCE concentrations (0.1% and 1%) or sterile water. The control group remained untreated. The incisions were processed for wound tensile strength (TS) measurement whereas the open wounds were subjected to histological examination. On the in vitro level the HCE extract induced fibronectin-rich extracellular matrix formation, but did not induced α-smooth muscle actin (SMA) expression in dermal fibroblasts. The animal study revealed that HCE increased wound TS and improved collagen organization. In conclusion, the direct comparison of both basic wound models demonstrated that the healing was significantly increased following HCE, thus this extract may be found useful to improve healing of acute wounds. Nevertheless, the use of an experimental rat model warrants a direct extrapolation to the human clinical situation.
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Aesculus/química , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Extratos Vegetais/química , Ratos , Regeneração , Resistência à TraçãoRESUMO
Chalcones are naturally occurring phytochemicals with diverse biological activities including antioxidant, antiproliferative, and anticancer effects. Some studies indicate that the antiproliferative effect of chalcones may be associated with their pro-oxidant effect. In the present study, we evaluated contribution of oxidative stress in the antiproliferative effect of acridine chalcone 1C ((2 E)-3-(acridin-9-yl)-1-(2,6-dimethoxyphenyl)prop-2-en-1-one) in human colorectal HCT116 cells. We demonstrated that chalcone 1C induced oxidative stress via increased reactive oxygen/nitrogen species (ROS/RNS) and superoxide production with a simultaneous weak adaptive activation of the cellular antioxidant defence mechanism. Furthermore, we also showed chalcone-induced mitochondrial dysfunction, DNA damage, and apoptosis induction. Moreover, activation of mitogen activated phosphokinase (MAPK) signalling pathway in 1C-treated cancer cells was also observed. On the other hand, co-treatment of cells with strong antioxidant, N-acetyl cysteine (NAC), significantly attenuated all of the above-mentioned effects of chalcone 1C, that is, decreased oxidant production, prevent mitochondrial dysfunction, DNA damage, and induction of apoptosis, as well as partially preventing the activation of MAPK signalling. Taken together, we documented the role of ROS in the antiproliferative/pro-apoptotic effects of acridine chalcone 1C. Moreover, these data suggest that this chalcone may be useful as a promising anti-cancer agent for treating colon cancer.
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Acridinas/farmacologia , Chalcona/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Chalcona/metabolismo , Chalconas/farmacologia , Humanos , Estresse Oxidativo/fisiologia , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
In recent decades, several spices have been studied for their potential in the prevention and treatment of cancer. It is documented that spices have antioxidant, anti-inflammatory, immunomodulatory, and anticancer effects. The main mechanisms of spices action included apoptosis induction, proliferation, migration and invasion of tumour inhibition, and sensitization of tumours to radiotherapy and chemotherapy. In this study, the ability of clove buds extract (CBE) to induce oxidative stress, DNA damage, and stress/survival/apoptotic pathways modulation were analysed in MCF-7 cells. We demonstrated that CBE treatment induced intrinsic caspase-dependent cell death associated with increased oxidative stress mediated by oxygen and nitrogen radicals. We showed also the CBE-mediated release of mitochondrial pro-apoptotic factors, signalling of oxidative stress-mediated DNA damage with modulation of cell antioxidant SOD (superoxide dismutase) system, and modulation activity of the Akt, p38 MAPK, JNK and Erk 1/2 pathways.
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Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Syzygium/química , Antineoplásicos Fitogênicos/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Humanos , Células MCF-7 , Extratos Vegetais/químicaRESUMO
BACKGROUND: Multiprofessional teamwork in physical and rehabilitation medicine (PRM) allows achieving patient-centered goals in accordance with the assumptions of the bio-psycho-social model of functioning. Team composition and methods of collaboration depend of the specificity of goals to be achieved, as well local contextual factors. International comparative studies on rehabilitation teamwork are lacking, despite data on how teams differ between countries are crucial for the process of harmonization of PRM practice across Europe. AIM: To compare models of collaboration within rehabilitation teams in Central Europe. DESIGN: A cross-sectional explorative study. SETTING: The data were collected in Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Slovakia between February and June 2018. POPULATION: PRM physicians. METHODS: An anonymous questionnaire inquiring of rehabilitation teamwork details was spread through national PRM societies, and other organizations associating PRM physicians. An ordered logit regression was applied to analyze the results. RESULTS: Responses were obtained from 455 respondents. Significant differences between the studied countries in the composition of rehabilitation teams and frequencies of team meetings were detected. In the analyzed population of PRM physicians, we found positive associations between the chance of participation in team meetings and working in a hospital, the amount of time devoted to PRM practice, and older age. The chance for patients and caregivers to participate in rehabilitation team meetings was correlated with PRM physician's hospital practice, activity as a PRM teacher, older age and devoting more time to PRM practice. Country specificities of rehabilitation team content were analyzed with regards to local economic, legal, and historical backgrounds, and availability of human resources. Underrepresentation of key professionals (e.g. occupational therapists, orthotists/prosthetists), inadequate distribution of professionals in healthcare and as well as outdated educational systems in some countries may affect the efficacy of the comprehensive care in rehabilitation. CONCLUSIONS: Central European countries differ in rehabilitation teamwork with regard to the contribution of professionals, meeting frequencies, and participation of patients and caregivers. Well-designed studies on teamwork models delineating ways to improve teamwork efficacy are in demand. CLINICAL REHABILITATION IMPACT: Between-country diversity of rehabilitation team content should be considered while planning activities aimed at European harmonization of PRM practice.
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Comunicação Interdisciplinar , Equipe de Assistência ao Paciente , Assistência Centrada no Paciente , Medicina Física e Reabilitação/organização & administração , Estudos Transversais , Europa (Continente) , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND/AIM: Development of new potential drugs to overcome multidrug resistance to chemotherapy is a big challenge for cancer treatment. Attention is also given to the natural compounds and their derivatives. The study aimed at evaluating the impact of a new chalcone derivative (1C) on multidrug resistant cell lines, focusing on P-glycoprotein (P-gp, ABCB1) inhibition, as well as 1C-doxorubicin interaction in vitro. MATERIALS AND METHODS: Cytotoxic and antiproliferative effects of the 1C compound were assessed by thiazolyl blue tetrazolium bromide (MTT) method in mouse T-cell lymphoma and human colon adenocarcinoma cells expressing ABCB1. Alterations in ABCB1 activity were evaluated by rhodamine 123 accumulation assay using flow cytometry. Drug-drug interaction was studied using combination assay. RESULTS: Our results confirmed antiproliferative, cytotoxic, as well as ABCB1 inhibitory potential of 1C in both tested ABCB1-expressing cancer cell lines. Furthermore, 1C displayed synergistic interaction with doxorubicin. CONCLUSION: Our results suggest the 1C chalcone derivative as a promising compound against resistant lymphoma and colon cancer, which could be used in monotherapy or in combination with other chemotherapeutics.
Assuntos
Adenocarcinoma/metabolismo , Chalconas/farmacologia , Neoplasias do Colo/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linfoma de Células T/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Adenocarcinoma/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Regulação para Baixo , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Linfoma de Células T/tratamento farmacológicoRESUMO
BACKGROUND: Tsetse flies (Glossina sp.) are the vectors of human and animal trypanosomiasis throughout sub-Saharan Africa. Tsetse flies are distinguished from other Diptera by unique adaptations, including lactation and the birthing of live young (obligate viviparity), a vertebrate blood-specific diet by both sexes, and obligate bacterial symbiosis. This work describes the comparative analysis of six Glossina genomes representing three sub-genera: Morsitans (G. morsitans morsitans, G. pallidipes, G. austeni), Palpalis (G. palpalis, G. fuscipes), and Fusca (G. brevipalpis) which represent different habitats, host preferences, and vectorial capacity. RESULTS: Genomic analyses validate established evolutionary relationships and sub-genera. Syntenic analysis of Glossina relative to Drosophila melanogaster shows reduced structural conservation across the sex-linked X chromosome. Sex-linked scaffolds show increased rates of female-specific gene expression and lower evolutionary rates relative to autosome associated genes. Tsetse-specific genes are enriched in protease, odorant-binding, and helicase activities. Lactation-associated genes are conserved across all Glossina species while male seminal proteins are rapidly evolving. Olfactory and gustatory genes are reduced across the genus relative to other insects. Vision-associated Rhodopsin genes show conservation of motion detection/tracking functions and variance in the Rhodopsin detecting colors in the blue wavelength ranges. CONCLUSIONS: Expanded genomic discoveries reveal the genetics underlying Glossina biology and provide a rich body of knowledge for basic science and disease control. They also provide insight into the evolutionary biology underlying novel adaptations and are relevant to applied aspects of vector control such as trap design and discovery of novel pest and disease control strategies.