Adenine phosphoribosyl transferase deficiency leads to renal allograft dysfunction in kidney transplant recipients: a systematic review / A deficiência de adenina fosforibosiltransferase leva à disfunção do aloenxerto renal em receptores de transplante renal: uma revisão sistemática

Abstract Background: Adenine phosphoribosyl transferase (APRT) deficiency has great implications on graft survival in kidney transplant patients. This systematic review investigated the diagnostic pattern, treatment approach, and kidney transplant outcomes among kidney transplant patients with adenine phosphoribosyl transferase deficiency. Material and methods: Articles reporting the APRT enzyme deficiency and kidney allograft dysfunction were retrieved from PubMed/Medline, ScienceDirect, Cochrane library and Google scholar databases. Descriptive analysis was used to draw inferences. Results: The results from 20 selected studies covering 30 patients receiving 39 grafts had an average age of 46.37 years are presented. Graft survival time of more than 6 months was reported in 23 (76.7%) patients, while other 7 (23.3%) patients had graft survival time of less than 6 months. Only 4 (13.3%) patients had APRT deficiency before transplantation. After follow-up, one-third of the patients 10 (33.3%) had stable graft function, 1 patient had allograft loss, 8 (26.6%) patients had delayed graft function while the remaining 11 (36.6%) patients had chronic kidney graft dysfunction. Conclusions: APRT deficiency is an under-recognized, treatable condition that causes reversible crystalline nephropathy, leading to loss of allograft or allograft dysfunction. The study results showed that inclusion of genetic determination of APRT deficiency in the differential diagnosis of crystalline nephropathy, even in the absence of a history of nephrolithiasis, can improve renal outcomes and may improve allograft survival.

Resumo Antecedentes: A deficiência de adenina fosforibosiltransferase (APRT) tem grandes implicações na sobrevida do enxerto em pacientes transplantados renais. Esta revisão sistemática investigou o padrão diagnóstico, a abordagem de tratamento e os desfechos do transplante renal entre pacientes transplantados renais com deficiência de adenina fosforibosiltransferase. Material e métodos: Os artigos que relatam sobre a enzima APRT e a disfunção do aloenxerto renal foram recuperados do PubMed/Medline, ScienceDirect, Biblioteca Cochrane e bancos de dados do Google Acadêmico. Utilizou-se a análise descritiva para extrair inferências. Resultados: Foram incluídos participantes que receberam 39 enxertos, a maioria dos quais provenientes de doadores vivos seguidos por doadores falecidos e doadores cadáveres. Foi relatado tempo de sobrevida do enxerto superior a 6 meses em 23 (76,7%) pacientes, enquanto outros 7 (23,3%) pacientes tiveram tempo de sobrevida do enxerto inferior a 6 meses. Apenas 4 (13,3%) pacientes apresentaram deficiência de APRT antes do transplante. Após acompanhamento, um terço dos pacientes, 10 (33,3%) apresentaram função do enxerto estável, 1 paciente teve perda do aloenxerto, 8 (26,6%) pacientes apresentaram função retardada do enxerto, enquanto os 11 (36,6%) pacientes restantes tiveram disfunção crônica do enxerto renal. Conclusões: A deficiência de APRT é uma causa subestimada e reversível de nefropatia cristalina que leva à disfunção do aloenxerto renal ou à perda total do aloenxerto. Os resultados deste estudo pedem a inclusão desta condição no diagnóstico diferencial de nefropatia cristalina, mesmo na ausência de um histórico de nefrolitíase.

Use of Omega3 (PUFA) as a major Complementary and alternative Medicine (CAM) and Mind-body therapies to fight against the Breast Cancer in Ethiopian Women. A Case study

In our study the participants mean age was 44.5 ± 6.4, the breast cancer history of the participants are 21 (14%), the breast cancer in married women is high total 125(83.33), Ethiopian breast cancer patients most education is STD 12th is 75 (50%), most of the patients having the occupation is housework 70(46.66, smoker was 10(6.66), alcoholic were 7(4.66) the most interesting observation is the total 133(88.66) were having no addiction. Complementary medicines PUFA had been taken by the participants were total 110 (73.33), antioxidants taken by patients were 100(66.66), Vitamin Supplement taken by patients was total 109(72.66), DHA taken by patients were total 118 (78.66). These complementary medicines and mind-body therapies can be coupled with therapeutic strategies that collectively enhance breast cancer treatment efficacy and improve the prognosis for long term survival.

Dihydroartemisinin and its anticancer activity against endometrial carcinoma and cervical cancer: involvement of apoptosis, autophagy and transferrin receptor

INTRODUCTION@#Dihydroartemisinin (DHA) is a first-line antimalarial drug with relatively low toxicity. DHA has been speculated to possess a broad-spectrum antitumour effect. However, the potential value of DHA for the treatment of endometrial carcinoma or cervical cancer is unclear.@*METHODS@#We used human endometrial cancer cells and cervical cancer cells to assess whether DHA alone or when combined with cisplatin would induce cell death. We aimed to elucidate the role of autophagy in DHA-induced cytotoxicity in both endometrial and cervical cancer cells, and explore the impact of DHA treatment on cell proliferation, apoptosis and autophagy.@*RESULTS@#DHA alone or in combination with cisplatin induced cell death in a dose- and time-dependent manner. Caspase-3 mRNA and cleaved caspase-3 protein levels were markedly elevated following DHA treatment either in the presence or absence of cisplatin, suggesting a role of apoptosis in DHA-induced cell death. DHA treatment activated the autophagic pathway, as evidenced by increased monodansylcadaverine-positive staining, elevated microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I ratio, and enhanced p62/sequestosome 1 degradation. Inhibition of autophagy by 3-methyladenine further enhanced the cytotoxicity of DHA towards tumour cells. mRNA levels of transferrin receptor (TfR) were suppressed upon DHA treatment and knockdown of TfR by RNA interference caused further DHA induction of cancer cell death.@*CONCLUSION@#Our results suggest a clinical value for DHA in the treatment of endometrial carcinoma and cervical cancer. Our data revealed possible anticancer mechanisms of DHA that involve regulating apoptosis, autophagy pathway and levels of TfR.

Effect of Arsenic Trioxide Combined with Dihydroartemisinin on THP-1 Cells Proliferation and Apoptosis / 中国实验方剂学杂志

Objective:To investigate the effects of arsenic trioxide combined with dihydroartemisinin on proliferation, cell cycle, and apoptosis of THP-1 cells, and explore the mechanism. Method:The thiazolyl blue （MTT） method was applied to detect the effect of different concentrations of arsenic trioxide, dihydroartemisinin and arsenic trioxide combined with dihydroartemisinin on the proliferation of THP-1 cells. Annexin V/propidium iodide（PI）assay was used to detect the change of THP-1 cell cycle and apoptosis．Western blot was performed to assess the expression of cysteine protease-3（Caspase-3）, cleaved Caspase-3, B-lymphocytoma-2（Bcl-2） and Bcl-2 associated X protein （Bax）. The changes of cell morphology were observed under high intension microscope. Result:Compared with blank group, arsenic trioxide and dihydroartemisinin both exhibited obvious antiproliferative effect on the human acute monocytic leukemia cell line THP-1 in time-dose dependence （P<0.01）. After 48 h, compared with the same dose of arsenic trioxide or that of dihydroartemisinin alone, the inhibition effect of 1 µmol·L-1 arsenic trioxide combined with 2 µmol·L-1 dihydroartemisinin on proliferation of THP-1 cells was significantly stronger （P<0.01）. Compared with the control group, arsenic trioxide combined with dihydroartemisinin significantly arrested the cells in G1 phase （P<0.01）, induced the downregulation of Caspase-3 and Bcl-2 （P<0.01） and upregulation of cleaved Caspase-3 significantly（P<0.05）. Conclusion:Arsenic trioxide combined with dihydroartemisinin can significantly inhibit the proliferation and induce apoptosis of THP-1 cells. The possible mechanism may be related to arrest the cells in G1 phase, reduce the expression of Caspase-3 and Bcl-2, increase the expression of cleaved Caspase-3.

Preliminary study of dihydroartemisin in inhibiting invasion and metastasis of hepatoma cells / 中国中药杂志

It is reported that dihydroartemisinin could reduce the expression of phosphorylated adhesion kinase and matrix metalloproteinase-2, inhibit the growth, migration and invasion of ovarian cancer cells, promote the formation of Treg cells through TGF-beta/Smad signaling pathway, and play an immunosuppressive role; dihydroartemisinin could also inhibit the growth of lung cancer cells by inhibiting the expression of vascular endothelial growth factor(VEGF) receptor KDR. However, there are few studies on dihydroartemisinin in hepatocellular carcinoma cells. In order to preliminarily explore the effect of dihydroartemisinin on invasion and metastasis of hepatocellular carcinoma cells, CCK-8 method and crystal violet staining were used to detect the effect of dihydroartemisinin on the growth of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H. The effects of dihydroartemisinin on the invasion and metastasis of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H were studied by using cell wound healing and Transwell. Western blot was used to detect the protein expression of epidermal growth factor receptor(EGFR) and its downstream signaling pathway in cells treated with dihydroartemisinin for 48 hours. The results showed that dihydroartemisinin could inhibit the growth of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H at 25 μmol·L~(-1). As compared with the control group, the number of cell clones was significantly reduced, and the ability of cell migration and invasion was weakened. Western blot results showed that as compared with the control group, dihydroartemisinin group could down-regulate the protein expression of EGFR and its downstream signaling pathways p-AKT, p-ERK, N-cadherin, Snail and Slug, and up-regulate the expression of E-cadherin protein, thus affecting the migration, invasion and metastasis of hepatocellular carcinoma cells 7402 and MHCC97 H.

Ácidos grasos en cepas de microalgas del Banco de Germoplasma de Organismos Acuáticos del Instituto del Mar del Perú (IMARPE)

Se determinó la composición de ácidos grasos de 54 cepas microalgales colectadas del Perú y mantenidas en el Banco de Germoplasma de Organismos Acuáticos (IMARPE) con la finalidad de determinar su uso nutricional en la acuicultura. Para ello se realizaron cultivos en un volumen de 50 mL y se determinaron los porcentajes relativos de ácidos grasos mediante transesterificación directa y cromatografía de gases. En el grupo Chlorophyta las microalgas que presentaron los mayores valores de porcentaje relativo de ácidos grasos fueron Chlamydomonas reinhardtii (16:0; 41.2%), Scenedesmus obtusus (18:1n-7; 33.6%), Acutodesmus dimorphus (18:1n-9; 37.1%), Desmodesmus armatus (18:3n-3; 32.2%) y Tetraselmis contracta (16:4n-3; 16.5%). En cambio en el grupo Bacillariophyta, los ácidos grasos más abundantes fueron 16:1n-7 en Chaetoceros didymus (20.2%), 18:4n-3 en Navicula sp. (28.3%) y EPA en Asterionellopsis sp. (31.5%). Por otro lado, en el grupo Dinophyta, todas las cepas superaron el 20% de DHA, en particular, la cepa de Akashiwo sanguinea presentó el mayor porcentaje relativo de este ácido graso (29.9%) y de los ácidos grasos 16:0 (24.8%) y EPA (16%). Se discute el uso de estas cepas según su contenido de ácidos grasos.

In This work, we determinate the fatty acids composition and their nutritional value in 54 microalgal strains, collected from Peru and stored in Banco de Germoplasma de Organismos Acuáticos (IMARPE). The cultures were grown to 50 mL and analyzed by direct transesterification and gas chromatography. In the Chlorophyta group, the microalgaes that present the highest relative percentage of fatty acids were Chlamydomonas reinhardtii (16:0; 41.2%), Scenedesmus obtusus (18:1n-7; 33.6%), Acutodesmus dimorphus (18:1n-9; 37.1%), Desmodesmus armatus (18:3n-3; 32.2%) and Tetraselmis contracta (16:4n-3; 16.5%). Moreover in the Bacillariophyta group, the most abundant fatty acids were 16:1n-7 in Chaetoceros didymus (20.2%), 18:4n-3 in Navicula sp. (28.3%) and EPA in Asterionellopsis sp. (31.5%). By the other hand, in the Dinophyta group, all strains exceed the 20% of DHA, in particular Akashiwo sanguinea, it was strain to have the highest percentage of this fatty acid (29.9%) in addition to 16: 0 (24.8%) and EPA (16%). We discussed uses of these strains is according to their fatty acids content.

Avaliação do perfil lipídico de ovos comerciais enriquecidos com omega 3 / Lipid profile of eggs with fatty acids omega 3

Objetivou-se com este estudo determinar o perfil de ácidos graxos de ovos comercializados como enriquecidos com ω3. Para o estudo foram adquiridas cartelas de uma dúzia de ovos de diferentes marcas comerciais. A determinação do perfil lipídico foi realizada a partir do ovo inteiro, sendo realizada a extração dos lipídeos, seguido de esterificação e análise cromatográfica para a identificação dos de ácidos graxos. Ocorreu uma maior variação entre os produtos para os ácidos graxos monoinsaturados e poli-insaturados. Para os teores de ácidos graxos ω3 ocorreu variação de 0,77 a 34,51%, principalmente para EPA que variou de 0,01 a 6,50% e, DHA que variou de 0,51 a 27,19%. Para ω6 os valores variaram de 5,35 a 21,91%. A quantidade de ácidos graxos ω3 em ovos enriquecidos é variável nos produtos, o que denota uma necessidade de padronização.

Perfil lipidico de produtos comercializados como fonte de omega 3 / Lipid profile of products with fatty acids omega 3

O presente estudo foi realizado com o objetivo de avaliar o perfil lipídico de produtos comercializados como enriquecidos com ácidos graxos ω3. Foi realizada a extração, esterificação e determinação cromatográfica dos ácidos graxos. Foram encontradas maiores concentrações dos ácidos graxos (C18:2ω6c), total de ácidos graxos ω6 e maior relação ω6/ ω3 para margarina. O salmão apresentou os maiores valores para os ácidos graxos C18:1ω9C, C18:3ω3 e total de monoinsaturados. Nas avaliações do suplemento foram encontradas as maiores concentrações dos ácidos graxos C20:5ω3 (EPA), C22:6ω3 (DHA) e total de ω3. Nos alimentos que são enriquecidos com ω3, a quantidade de EPA e DHA são baixas, sendo maiores de ácido linolênico (C18:3ω3). Nutricionalmente o suplemento de EPA e DHA e o salmão foram as melhores fontes de ácidos graxos ω3. E, todos os produtos apresentaram bons índices de aterogenicidade e trombogenicidade.

Screening for hyper-accumulating lipid mutants in Aurantiochytrium limacinum using high-throughput fluorescence-based method / 生物工程学报

Docosahexaenoic acid (DHA) has many unique physiological functions such as promoting the development of brain and retina in infants. Therefore, it is widely applied to food, pharmacy, breeding and other industries. To obtain engineered strains of Aurantiochytrium limacinum SR21 suitable for industrial application with increased lipid and DHA production, we designed a simple, fast, accurate and high-throughput screening method based on Nile red staining of oil droplets. First, ultraviolet C (UVC) mutagenesis was used to generate a random mutant library of A. limacinum. Second, screening conditions were optimized including staining conditions of Nile red and the sorting criterion. Thereby, three putative high-lipid mutants (D03432, D05106 and D01521) were selected from the mutant library containing 3 648 mutated clones. The three mutants grew faster and produced higher amounts of lipids and DHA compared to wild type (WT). In 100 mL cultures, the lipid content of D03432 and D05106 mutants reached 64.74% and 63.13% of dry cell weight respectively, whereas the wild strain exhibited only 43.19%. DHA yield in these two mutants were even 2.26-fold and 2.37-fold higher than that of the wild strain. Experiment with 5 L fermentor further confirmed that D03432 and D05106 mutants had better performance than the wild strain on DHA yield (45.51% and 66.46% more than that of the wild strain, respectively), and demonstrated their high potential for industrial application. This work not only generated several high-DHA content mutants with high potential for industrial use, but also provided vital guidance for high-throughput screening of lipid hyper-accumulating mutants in other oil-producing microorganisms.

Risk Assessment of “Other Substances” –Eicosapentaenoic Acid, Docosapentaenoic Acid and Docosahexaenoic Acid

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of “other substances” in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating the addition of “other substances” to food supplements and other foods. “Other substances” are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional or physiological effect. The substance is added mainly to food supplements, but also to energy drinks and other foods. VKM has not in this series of risk assessments of “other substances” evaluated any potential beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) in food supplements, and is based on previous risk assessments and a literature search. It is emphasised that this risk assessment concerns the single fatty acids EPA, DPA or DHA separately and not mixtures of these as found in e.g. fish oil/cod liver oil. For risk assessment of combined mixtures of n-3 LCPUFAs in e.g. fish oil/cod liver oil, see the EFSA opinion from 2012 or the VKM assessment from 2011 (EFSA, 2012; VKM, 2011). In the reviewed literature of this risk assessment, no studies investigating ratios between EPA, DPA, DHA or other fatty acids in mixtures have been identified. EPA, DPA and DHA are long chain n-3 polyunsaturated fatty acids (n-3 LCPUFA) and in food these fatty acids are incorporated in triacylglycerols (TAGs) and phospholipids (PLs). Dietary sources are fatty fish, cod liver-, seal-, whale-, fish- and krill oils and human milk, containing various ratios of these fatty acids in combination. EPA can be metabolised to eicosanoids such as prostaglandins, prostacyclins and leukotrienes, all groups are biologically active substances. The eicosanoids participate in the regulation of blood pressure, renal function, blood coagulation, inflammatory and immunological reactions. DHA is an essential structural component of the brain, skin, sperm, testicles and retina. DPA can be retro-converted to EPA or converted to DHA. Still little is known of the biological effects of DPA. Humans have a limited capacity to synthesise EPA, DPA and subsequently DHA from the precursor alpha-linolenic acid (ALA), and this endogenous production is negligible in comparison to the doses used in supplementation studies. According to information from the NFSA, EPA, DPA and DHA are food supplement ingredients in Norway, and NFSA has requested a risk assessment of these fatty acids in the following doses in food supplements: EPA: 1500, 1750 and 1825 mg/day DPA: 100, 125 and 150 mg/day DHA: 1050 and 1290 mg/day Children below 10 years were not included in the terms of reference. Information about intake of EPA, DPA and DHA from the diet is scarce, but calculations performed in the Norwegian Mother and Child Cohort Study indicate a mean total intake (SD) from food and supplements of EPA around 330 (340) mg/day, DPA 43 (30) mg/day and DHA 430 (380) mg/day among pregnant women (2002 to 2008). Mean combined intake of EPA, DPA and DHA from fish oil/ cod liver oil in adults participating in a nationally representative dietary survey was 735 mg/day (VKM, 2014). The major concerns with high intake of EPA and DHA have been increased bleeding time, adverse effects related to immune function, lipid peroxidation and glucose homeostasis. EFSA concluded in 2012 that long-term supplemental intakes of 5 g/day of the n-3 LCPUFA do not raise safety concerns for adults with regard to an increased risk of spontaneous bleeding episodes or bleeding complications, or affect glucose homeostasis, immune function or lipid peroxidation. In 2011, VKM concluded that an intake n-3 LCPUFA up to 6.9 g/day was not associated with increased risk of any serious adverse events. Some adverse health effects related to gastrointestinal function, including abdominal cramps, flatulence, eructation, vomiting and diarrhea have been reported, but seem to be associated with intake of an oily substance and not related specifically to EPA, DPA and/or DHA. EPA: In the report from 2012, EFSA concluded that 1.8 g/day of supplemental EPA does not raise safety concerns in adults. None of the included studies from our literature searches limited to 2012 and onwards have investigated bleeding complications. The dosages of EPA in the three included studies in this report range from 1.8 to 3.8 g/day for 12 weeks. The main endpoints in the studies included lipid peroxidation, inflammation biomarkers of cardiovascular diseases and no serious adverse events were found related to the main endpoints. In general, adverse events were described as gastrointestinal discomforts and not related to dosage. Studies of longer duration are necessary before an intake above 1.8 g of EPA can be considered safe. The Norwegian Scientific Committee for Food Safety (VKM) concludes that the specified doses of 1500, 1750, 1825 mg/day of EPA in food supplements are unlikely to cause adverse health effects in adults (≥18 years). In 2012, EFSA did not make conclusions for children or adolescents for EPA. No new studies with EPA supplementation have been identified in children or adolescents after 2012, and therefore no risk assessment can be made for children (≥10 years) or adolescents. DPA: No dosage of DPA in food supplements can be evaluated due to lack of data. DHA: EFSA concluded that 1 g/day of supplemental DHA does not raise safety concerns for the general population (including children and adolescents). The dosages of DHA in the included trials in this report range from 1.0 to 3.6 g/day and the duration from five weeks to four years. Six out of seven studies have used dosages from 1 to 2 g DHA/day. The last study included up to 3.6 g DHA/day for four years and the age spanned from 7 to 31 years. The main endpoints in all studies included lipid peroxidation, inflammation, cognitive performance, blood pressure and biomarkers of cardiovascular diseases and no serious adverse events were found related to the main endpoints. In general, adverse events were described as gastrointestinal discomforts and not related to dosage. VKM therefore considers that the specified daily doses of DHA that moderately exceed 1 g per day (1050 and 1290 mg/day) are unlikely to cause adverse health effects in the general population including children ≥10 years and adolescents. VKM concludes that the specified doses of 1050 and 1290 mg/day of DHA in food supplements are unlikely to cause adverse health effects in the general population including children (≥10 years), adolescents and adults (≥18 years).

Alanine mother liquor as a nitrogen source for docosahexaenoic acid production by Schizochytrium sp. B4D1

Alanine mother liquor, a type of industrial waste from alanine fermentation, was used as a nitrogen source to produce docosahexaenoic acid (DHA) by Schizochytrium sp. B4D1. The results indicated that yeast extract could trigger the utilization of the alanine mother liquor. Additionally, the alanine can be quenched during the culture, which aids in DHA accumulation. The medium components were optimized via response surface methodology as follows: 99.98-g/L glucose, 0.05-g/L yeast extract and a 183.17 dilution factor of the alanine mother liquid (v/v, with an alanine content of 0.72 g/L) and 17.98% inoculum concentration (v/v). Finally, in a 50-mL shake-flask fermentation, the DHA yield was 2.29 g/L.

Interferências da suplementação de óleo de peixe na qualidade de vida de pacientes em tratamento neoadjuvante de carcinoma de reto / Interferences of fish oil supplementation in the quality of life of patients in neoadjuvant treatment for rectum carcinoma

Introdução: Segundo a Organização Mundial de Saúde qualidade de vida (QV) compreende "a percepção do ser humano de sua posição na vida no contexto da cultura e sistema de valores nos quais ele vive e em relação aos seus objetivos, expectativas, padrões e preocupações". Já foi comprovado os benefícios da terapia neoadjuvante na redução do risco de recorrência local, melhora da margem de ressecção cirúrgica e maiores chances de cura através da resposta patológica completa. Porém, apesar dos benefícios desses tratamentos, existem efeitos adversos relacionados à toxicidade e complicações cirúrgicas e pós-cirúrgicas que interferem drasticamente na qualidade de vida dos pacientes. Em estudos pré-clínicos a incorporação de ácidos graxos eicosapentaenoico (EPA) e docosaexaenoico (DHA) - provenientes do óleo de peixe - tem mostrado interferir em vias de inflamação, sinalização celular e transcrição gênica melhorando a resposta ao tratamento e consequentemente a qualidade de vida. Objetivo: O objetivo primário desta pesquisa foi verificar se o consumo diário de 2,4g de EPA+DHA concomitante a terapia neoadjuvante e até um dia antes da cirurgia interferiria na qualidade de vida de pacientes com câncer de reto durante o tratamento. Os objetivos secundários foram avaliar complicações intra e pós-cirúrgicas, resposta patológica e estado nutricional dos pacientes e relacionar essas informações com qualidade de vida e ingestão de óleo de peixe. Metodologia: Um total de 111 pacientes com adenocarcinoma de reto foram randomizados quanto à suplementação diária de 2,4 g de EPA+DHA concomitante ao tratamento neoadjuvante. Após necessidade de exclusão de alguns pacientes 106 estavam aptos para participação das avaliações do projeto, que aconteceram em cinco momentos: M1 - pré-tratamento, M2 - ao termino da quimioradioterapia, M3 - quatro semanas após quimioradioterapia e M4 - um dia antes da cirurgia. No pós-operatório as informações foram adquiridas através do prontuário eletrônico. A qualidade de vida foi avaliada através dos questionários da Organização Europeia de Pesquisa e Tratamento do Câncer, EORTC QLQ-C30 e QLQ-CR29, que foram aplicados em todos os momentos do estudo. Resultados: Não houve diferenças significativas entre os grupos controle (GC) e o grupo intervenção (GI) quanto as características sociodemográficas e clínicas. Com relação às variáveis do estado nutricional foi possível perceber que a quimioradioterapia resultou em deterioração do estado nutricional em ambos os grupos sendo percebida melhora do estado nutricional no M3 e M4, não havendo, porém, diferenças significativas entre os grupos para todas as variáveis. Os resultados dos questionários de qualidade de vida mostraram no M1 (primeira avaliação) que o GC se apresentava mais sintomático para disúria (P = 0,041) e distensão abdominal (P = 0,036), sendo que ao final da radio e quimioterapia o sintoma disúria permaneceu prevalente para o GC (P = 0,031). No M3 o GI apresentou-se menos sintomático para dor (P = 0,045), dor anorretal (P = 0,009) e dispaurenia (P = 0,041), e para escala de função apresentou menos ansiedade (P = 0,033) quando comparados ao GC. Um dia antes da cirurgia (M4) o GC apresentou-se com maior perda de apetite (P = 0,016) e distensão abdominal (P = 0,007) quando comparado com o GI. Com relação aos efeitos adversos do tratamento neoadjuvante o GI apresentou-se com menor quantidade de sintomas relatados do que o GC (P = 0,045). Conclusão: A suplementação com EPA e DHA em pacientes com câncer de reto melhorou a QV ao diminuir disúria, dor, dor anorretal, dispaurenia, distensão abdominal, perda de apetite e ansiedade quando comparados ao GC e interferiu nos efeitos adversos da RDT e QT ao diminuir significativamente a quantidade de toxicidades relatadas pelos pacientes do GI quando comparados ao GC (AU)

Introduction: According to the Health World Organization, Quality of Life (QoL) comprises "the perception of a human being regarding their position in life in the context of culture and a value system in which they live, related to their goals, expectations, standards and concerns". The benefits of neoadjuvant therapy have already been proven, such as risk reduction of local recurrence, margin improvement of surgical resection and greater chances of cure through the complete pathological response. However, despite the benefits of these treatments, there are adverse effects related to toxicity and surgical and post-surgical complications which drastically interfere with patient's quality of life. In pre-clinical studies, the incorporation of fatty acids as eicosapentaenoic (EPA) and docosahexaenoic (DHA) ­ derived from fish oil ­ have shown to interfere in inflammation pathways, cellular signaling and gene transition, improving treatment response and therefore the quality of life. Objective: The primary goal of the present research was to verify if daily consumption of 2,4 g of EPA+DHA concomitant to neoadjuvant therapy and up to one day before surgery would interfere in patient's quality of life during treatment. The secondary objectives were to assess intra and post-surgical complications, pathological response and nutritional state of patients and to relate this information with quality of life and fish oil intake. Method: A total of 111 patients with rectum adenocarcinoma were randomly assigned for daily supplementation of 2,4 g of EPA+DHA concomitant to neoadjuvant treatment. After the need for exclusion of some patients 106 were suitable for participation in the projects assessments, which occurred in five moments: M1 ­ pre-treatment, M2 ­ at the end of chemoradiotherapy, M3 ­ four weeks after chemoradiotherapy and M4 ­ one day before surgery. At post-operative information were obtained through electronic record. Quality of life was assessed through the European Organization of Research and Treatment for Cancer, EORTC QLQ-C30 and QLQ-CR29, which were applied in all moments of the study. Results: There were no significant differences between control group (CG) and intervention group (IG) regarding sociodemographic and clinical characteristics. About nutritional state variables, it was possible to notice that chemoradiotherapy resulted in the deterioration of the nutritional state in both groups, improvement of the nutritional state was noticed in M3 and M4, however, there were no significant differences among groups for all variables. The results of quality of life questionnaires showed that in M1 (first assessment) the CG was presented more symptomatic for dysuria (P = 0,041) and abdominal distention (P = 0,036), in that at the end of radio and chemotherapy the dysuria symptom remained prevalent for CG (P = 0,031). In M3 the IG was presented less symptomatic for pain (P = 0,045), anorectal pain (P = 0,009) and dyspareunia (P = 0,041), and for scale function presented less anxiety (P = 0,033) when compared to the CG. One day before surgery (M4) the CG presented greater loss of appetite (P = 0,016) and abdominal distention (P = 0,007) when compared to the IG. Regarding adverse effects of neoadjuvant treatment, the IG presented less quantity of reported symptoms than the CG (P = 0,045). Conclusion: The supplementation with EPA and DHA in patients with rectum cancer improved QoL by decreasing dysuria, pain, anorectal pain, dyspareunia, abdominal distention, loss of appetite and anxiety when compared to the CG and interfered in the adverse effects of chemoradiotherapy by significantly decreasing the amount of toxicity reported by the IG patients when compared to the CG (AU)

Effect of dihydroartemisinin on permeability of human erythrocyte membrane infected plasmodium / 中国中药杂志

In view of the fact that the antimalarial effects of artemisinins are significant but the mechanism has not yet been clarified and there are many different opinions, it is possible that artemisinins can produce high anti-malarial efficacy through various mechanisms and multiple pathways. In addition, the researches on the pathogenesis of malaria "erythrocyte membrane plasmodial surface anion channel (PSAC)" in the past few years have provided more positive findings, which may confirm and discover the new antimalarial mechanism of artemisinins. This paper was as to study the effect of dihydroartemisinin (DHA) in vitro on erythrocyte membrane permeability of HB3 plasmodium infection, with using the mechanism of 5% sorbitol can be used to kill the Plasmodium falciparum in red blood cell membrane selectively, the effectual difference of sorbitol on the killing of P. falciparum with adding DHA or not was detected, so as to investigate whether DHA can affect the permeability of the erythrocyte membrane. Result showed that, Pre-stimulation with 10 nmol·L⁻¹ DHA (the final concentration of plasmodium in vitro culture system) for 30 min could significantly decrease the killing effect of sorbitol on the HB3 plasmodium in the P. falciparum erythrocytic cycle, and DHA may inhibit the permeability of the erythrocyte membrane for preventing sorbitol through the red blood cell membrane, thereby reducing the killing effect of sorbitol on the P. falciparum.

The effect of docosahexaenoic acid combined with cyclooxygenase-2 selective inhibitor NS-398 on the apoptosis of bile duct cancer cells QBC939 / 中华肝胆外科杂志

Objective To investigate the effect of docosahexaenoic acid (DHA) combined with cyclooxygenase-2 (COX-2) selective inhibitor NS-398 on the apoptosis of cholangiocarcinoma QBC939 cells and the mechanism.Methods In vitro,cholangiocarcinoma QBC939 cells were treated with 0,15,30,45,60 and 75 μg/ml DHA with 0,25,50,100,150 and 200 μmol/L NS-398,respectively.The absorbances of the QBC939 cells were measured by CCK8 and its growth inhibition ratios were analyzed.Flow cytometry was applied to detect cell apoptosis.The level of β-catenin and COX-2 mRNA and protein were measured by real-time PCR,immunocytochemistry and enzyme-linked immunoadsordent assay,respectively.Results DHA combined with NS-398 could significantly suppress the growth of QBC939 cells (P ＜ 0.05).When the concentration of DHA went up to 45 μg/ml and NS-398 was 100 μmol/L,the relative growth inhibition rate of QBC939 cells was 90.0％.If the concentrations were increased,the result showed no significant differences.Furthermore,flow cytometry analysis indicated that DHA combined with NS-398 could induce QBC939 cells apoptosis at the early stage,and the apoptosis rate was significantly different between the experimental and control groups (P ＜ 0.01).Real-time PCR showed low β-catenin and COX-2 expression in QBC939 cells disposed by DHA combined with NS-398,and their expression were significantly different between the experimental and control groups (P ＜ 0.01).Immunocytochemistry and ELISA demonstrated that DHA combined with NS-398 could decrease β-catenin and COX-2 protein expression in QBC939 cells.Conclusion DHA combined with NS-398 induced apoptosis and inhibited proliferation of cholangiocarcinoma cells QBC939 in vitro through targeting β-catenin and COX-2.

Effectiveness of omega-3 polyunsaturated fatty acids against microbial pathogens / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Microorganisms provide both beneficial and harmful effects to human beings. Beneficial effects come from the symbiotic relationship that exists between humans and microbiota, but then several human illnesses have turned some friendly microbes into opportunistic pathogens, causing several microbial-related diseases. Various efforts have been made to create and utilize antimicrobial agents in the treatment and prevention of these infections, but such efforts have been hampered by the emergence of antimicrobial resistance. Despite extensive studies on drug discovery to alleviate this problem, issues with the toxicity and tolerance of certain compounds and continuous microbial evolution have forced researchers to focus on screening various phytochemical dietary compounds for antimicrobial activity. Linolenic acid and its derivatives (eicosapentaenoic acid and docosahexaenoic acid) are omega-3 fatty acids that have been studied due to their role in human health, being important for the brain, the eye, the cardiovascular system, and general human growth. However, their utilization as antimicrobial agents has not been widely appreciated, perhaps due to a lack of understanding of antimicrobial mechanisms, toxicity, and route of administration. Therefore, this review focuses on the efficacy, mechanism, and toxicity of omega-3 fatty acids as alternative therapeutic agents for treating and preventing diseases associated with pathogenic microorganisms.

Selection of Schizochytrium limacinum mutants based on butanol tolerance

Background: Mutation breeding is one of the most important routes to achieving high docosahexaenoic acid (DHA) productivity using Schizochytrium. However, few selection strategies have been reported that aim to generate a high DHA content in Schizochytrium lipids. Results: First, culture temperature altered the butanol tolerance of Schizochytrium limacinum B4D1. Second, S. limacinum E8 was obtained by selecting mutants with high butanol tolerance. This mutant exhibited a 17.97% lower proportion of DHA than the parent strain S. limacinum B4D1. Third, a negative selection strategy was designed in which S. limacinum F6, a mutant with poor butanol tolerance, was obtained. The proportion of DHA in S. limacinum F6 was 11.22% higher than that of parent strain S. limacinum B4D1. Finally, the performances of S. limacinum B4D1, E8 and F6 were compared. These three strains had different fatty acid profiles, but there was no statistical difference in their biomasses and lipid yields. Conclusion: It was feasible to identified the relative DHA content of S. limacinum mutants based on their butanol tolerance.

A single administration of fish oil inhibits the acute inflammatory response in rats

Objective To investigate the antiinflammatory effects of a single administration of fish oil (FO) on the acute inflammatory response. Methods The paw edema and pleurisy models were used to evaluate the effects of FO dissolved in olive oil (FOP) orally administered in a single dose in rats. Nitric oxide (NO) concentrations in the pleural exudate were performed according to the Griess method and the cytokine concentrations were determined by Luminex bead-based multiplex assay. Results FOP treatment (30 and 300 mg/kg) significantly reduced paw edema. FOP treatment at 18.75, 37.5, 75.0, 150.0, and 300 mg/kg decreased both the volume of pleural exudate and cellular migration into the pleural cavity and each of these doses presented the same effectiveness. Treatment with FOP (300 mg/kg) reduced NO, TNF-α IL-1β and IL-6 concentrations in the pleural exudate. Conclusions The present data provide evidence that FO has inhibitory effects on the acute inflammatory response when administered in a single dose in rats. This effect might be attributable to a direct inhibitory effect of FO on the production or release of inflammatory mediators that are involved in the pathological processes evaluated herein.

A single administration of fish oil inhibits the acute inflammatory response in rats

OBJECTIVE@#To investigate the antiinflammatory effects of a single administration of fish oil (FO) on the acute inflammatory response.@*METHODS@#The paw edema and pleurisy models were used to evaluate the effects of FO dissolved in olive oil (FOP) orally administered in a single dose in rats. Nitric oxide (NO) concentrations in the pleural exudate were performed according to the Griess method and the cytokine concentrations were determined by Luminex bead-based multiplex assay.@*RESULTS@#FOP treatment (30 and 300 mg/kg) significantly reduced paw edema. FOP treatment at 18.75, 37.5, 75.0, 150.0, and 300 mg/kg decreased both the volume of pleural exudate and cellular migration into the pleural cavity and each of these doses presented the same effectiveness. Treatment with FOP (300 mg/kg) reduced NO, TNF-α, IL-1β, and IL-6 concentrations in the pleural exudate.@*CONCLUSIONS@#The present data provide evidence that FO has inhibitory effects on the acute inflammatory response when administered in a single dose in rats. This effect might be attributable to a direct inhibitory effect of FO on the production or release of inflammatory mediators that are involved in the pathological processes evaluated herein.

Chemopreventive and Chemotherapeutic Effects of Fish Oil derived Omega-3 Polyunsaturated Fatty Acids on Colon Carcinogenesis

Colorectal cancer is the third most common cause of cancer related death in the world. Multiple lines of evidence suggest that there is an association between consumption of dietary fat and colon cancer risk. Not only the amount but also the type and the ratio of fatty acids comprising dietary fats consumed have been implicated in the etiology and pathogenesis of colon cancer. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been known to inhibit development of colon cancer by downregulating the expression of genes involved in colon carcinogenesis and also by altering the membrane lipid composition. Data from laboratory, epidemiological, and clinical studies substantiate the beneficial role of n-3 PUFAs in preventing colitis and subsequent development of colon cancer. In addition, recent studies suggest that some n-3 PUFAs can be effective as an adjuvant with chemotherapeutic agents and other natural anticancer compounds in the management of colon cancer. In this review, we discuss chemopreventive and therapeutic effects of fish oil derived long chain n-3 PUFAs, particularly EPA and DHA, with focus on synergetic effects of which they exert when combined with chemotherapeutic agents and other natural compounds.

Strategy of oxygen transfer coefficient control on the L-erythrulose fermentation by newly isolated Gluconobacter kondonii

Background: The effect of diverse oxygen transfer coefficient on the L-erythrulose production from meso-erythritol by a newly isolated strain, Gluconobacter kondonii CGMCC8391 was investigated. In order to elucidate the effects of volumetric mass transfer coefficient (K La) on the fermentations, baffled and unbaffled flask cultures, and fed-batch cultures were developed in present work. Results: With the increase of the K La value in the fed-batch culture, L-erythrulose concentration, productivity and yield were significantly improved, while cell growth was not the best in the high K La. Thus, a two-stage oxygen supply control strategy was proposed, aimed at achieving high concentration and high productivity of L-erythrulose. During the first 12 h, Klawas controlled at 40.28 h-1 to obtain high value for cell growth, subsequently K La was controlled at 86.31 h-1 to allow for high L-erythrulose accumulation. Conclusions: Under optimal conditions, the L-erythrulose concentration, productivity, yield and DCW reached 207.9 ± 7.78 g/L, 6.50 g/L/h, 0.94 g/g, 2.68 ± 0.17 g/L, respectively. At the end of fermentation, the L-erythrulose concentration and productivity were higher than those in the previous similar reports.