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RESUMEN Introducción: La vitamina C es una sustancia que desde hace ya varios años ha suscitado debate debido a la cantidad de usos que se han demostrado. En algunos casos, las utilidades han ido desde profilaxis y acortamiento de la duración de resfriados, hasta estudios de acción en enfermedades, tales como el cáncer; los mecanismos de acción de esta han sido evaluados en forma de monoterapia o en combinación con quimioterapia para demostrar o descartar su utilidad en el cáncer. Objetivo: Demostrar si los efectos de la vitamina C fueron efectivos y si su uso, solo o en combinación con quimioterapia, es de utilidad. Método: Se realizó una investigación de tipo descriptiva documental, realizada con artículos científicos en el periodo comprendido desde 2016 hasta 2021, con un análisis detallado de los resultados del uso de la vitamina C y su posible efecto sobre los diferentes tipos de cáncer. Fueron buscados en las bases de datos de SciELO, Scopus y Medline. Resultados: La información hallada fue organizada según concentraciones plasmáticas de vitamina C y su acción en células cancerosas, dosis evaluadas de la vitamina C, mecanismos de acción en relación a células cancerígenas, desequilibrio redox, efecto específico en cánceres, vitamina C y cáncer de mama. Conclusiones: En la revisión realizada se evidencia que la vitamina C tiene un efecto benéfico en los cánceres hematopoyéticos, como: leucemia, melanoma, cáncer de mama o ciertos tipos de cáncer colorrectal y que disminuyen los efectos adversos producidos por medicamentos quimioterapéuticos.
ABSTRACT Introduction: Vitamin C is a water-soluble substance that has been in debate since a long time ago due to its wide demonstrated use. In some cases, its usage have ranged from prophylaxis and shortening the duration of colds, to studies of its action in diseases, such as cancer; Its mechanisms of action have been evaluated in the form of monotherapy or in combination with the chemotherapy to demonstrate or rule out its usefulness in cancer. Objective: To demonstrate whether the effects of vitamin C were effective and whether its use, alone or in combination with chemotherapy, is useful. Method: A documentary descriptive research was carried out, supported with scientific articles (period 2016 to 2021) which analyze in detail the results of the use of vitamin C and its possible effect on different types of cancer. Results: The information found was organized according to plasma concentrations of vitamin C, its action on cancer cells, evaluated doses of vitamin C, mechanisms of action in relation to cancer cells, redox imbalance, specific effect on cancers, vitamin C and breast cancer. Conclusions: The review shows that the use of vitamin C has a beneficial effect on hematopoietic cancers, such as leukemia, melanoma, breast cancer or certain types of colorectal cancer, and also reduces the adverse effects produced by chemotherapeutic drugs.
RESUMO Introdução: A vitamina C é uma substância que há vários anos desperta o debate devido ao número de usos que foram demonstrados. Em alguns casos, os benefícios vão desde a profilaxia e redução da duração dos resfriados, até estudos de ação em doenças, como o câncer; os mecanismos de ação deste foram avaliados como monoterapia ou em combinação com quimioterapia para provar ou descartar sua utilidade no câncer. Objetivo: Demonstrar se os efeitos da vitamina C foram eficazes e se seu uso, isoladamente ou em combinação com a quimioterapia, é útil. Método: Foi realizada uma pesquisa documental descritiva, realizada com artigos científicos no período de 2016 a 2021, com análise detalhada dos resultados do uso da vitamina C e seu possível efeito nos diferentes tipos de câncer. Eles foram pesquisados nas bases de dados SciELO, Scopus e Medline. Resultados: As informações encontradas foram organizadas de acordo com as concentrações plasmáticas de vitamina C e sua ação nas células cancerígenas, doses avaliadas de vitamina C, mecanismos de ação em relação às células cancerígenas, desequilíbrio redox, efeito específico sobre cânceres, vitamina C e câncer de mama. Conclusões: Na revisão realizada, fica evidente que a vitamina C tem efeito benéfico sobre os cânceres hematopoiéticos, como: leucemia, melanoma, câncer de mama ou certos tipos de câncer colorretal e que reduz os efeitos adversos produzidos pelos quimioterápicos.
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Context: The ongoing pandemic has affected all the spheres of life and one of the severely affected avenues is the education of a child. The online education has seen an upward curve since the start of COVID-19 pandemic. Schools globally have adopted online class tutorials as the main method to impart education and directly increasing the screen time for a child. Aim: The aim of the present study was to evaluate the cytological effects of prolonged mobile phone usage on the buccal mucosa of children. Settings and Design: Stratified sampling was used for the selection of subjects for the study. After a questionnaire regarding the usage of a mobile phone was distributed among the parents of children. Among them, 90 children were selected on the basis of pattern and frequency of mobile phone usage in the child. Materials and Methodology: The children were divided into three groups based on the per day hours of viewing of mobile phone, i.e., Group 1: Usage of 1–2 h a day, Group 2: Usage of 3–6 h a day, and Group 3: Usage of >6 h a day. The time frame taken into consideration was 1 year after the pandemic started. This was specifically to understand the impact of the online education. Swab was obtained by using the conventional ice-cream stick method from the buccal mucosa. Statistical Analysis: The samples were subjected to histological and microscopical analysis to observe for cytological changes. One-way ANOVA was used to determine the statistical significance if any. Results: The results obtained clearly showed that Group 3 (>6 h usage per day) showed the highest number of cellular and chromosomal aberrations which was significant. Conclusion: The results indicated that impact due to the prolonged screen time on the buccal mucosa is significant. A direct proportionality was seen between the apoptotic changes and chromosomal aberrations and the number of daily hour usage.
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@#Introduction: Hepatocellular carcinoma is one of the most common cancers that affected human in more than half of the world population. Although there is yet any alternatives treatment found for this disease, the antitumor property of thymoquinone has been well studied in most of cancer cell lines. Nonetheless, poor bioavailability of TQ limits its efficiency. The encapsulation form of TQ, TQ-NLC is suggested to enhance its bioavailability as well as cytotoxicity towards cancer cells via increasing resistance time and targeting drug to specified location in the body. Therefore, it is a great advantage to look at the effects of TQ-NLC towards HepG2. This study is design to look at the anti-proliferative effect of TQ-NLC on HepG2 and the changes in the cells morphology. Methods: Both cells were bought from ATCC and cultured in supplemented DMEM. Cell viability was determined via MTT assay. Pro-apoptotic effect of TQ-NLC was further confirmed with Annexin V staining. Morphology hallmarks of apoptosis of treated cells were also analysed using inverted microscope. Images were captured at 24, 48 and 72 hours. Results: TQ-NLC was very potent towards HepG2 compared to 3T3 with the relative IC50 of 25 µM. TQ-NLC was also more potent compared to the non-encapsulated form, TQ. Further analysis confirmed that TQ-NLC capable to increase the percentage of apoptotic cells in time-dependent manner. Qualitatively, all treated cells displayed the apoptosis morphology with increasing concentration and longer time-point. Conclusion: TQ-NLC showed greater cytotoxic effects towards HepG2 which was further confirmed with the morphological analysis
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NeoplasmsABSTRACT
Our bodies produce a lot of apoptotic cells every day,and the timely removal of these apoptotic cells is essential to maintain the immune balance of the body. In the removal of apoptotic cells,macrophages play a major role,and their removal process is divided into three stages:recruitment,identification and phagocytosis. In the recruitment stage,apoptotic cells secrete′find me′signals, and phagocytes respond and are recruited to apoptotic cells. At the identification stage, the ′eat-me′ signal of apoptotic cells was identified with the phagocytic receptor on the surface of phagocytes. Phagocytic phase, the ′eat-me′ signal transmits signals to macrophages,such as activating the small GTPase Rac1,which leads to actin polymerization and cytoskeleton rearrangement to promote the phagocytosis of apoptotic cells. If the removal mechanism of apoptotic cells is obstructive,the apoptotic cells that have not been cleared in time will enter the secondary necrotic state and release the self-antigens. These self-antigens may stimulate the body′s immune system to produce autoantibodies,leading to autoimmune diseases such as SLE. The research progress of the macrophage on the removal mechanism of apoptosis cells is reviewed in this paper.
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Phosphatidylserine (PS) is a phospholipid that is abundant in eukaryotic plasma membranes,has crucial biological functions.Under cell apoptosis, cells can not generate enough ATP for energy and the concentration of cytoplasmic Ca 2 +increases, resulting in PS eversion.Apoptosis and the clearance of apoptotic cells are essential processes in animal development and homeostasis.For apoptotic cells to be cleared, they must display aneat me signal, most likely PS exposure, which prompts phagocytes to engulf the cells.PS is exposed by the action of scramblase on the cell's surface in biological processes such as apoptosis and platelet activation.Once exposed to the cell surface, PS acts as an eat me signal on dead cells, and creates a scaffold for blood-clotting factors on activated platelets.The molecular identities of the flippase and scramblase that work at plasma membranes have long eluded researchers.Indeed, their identity as well as the mechanism of the PS exposure to the cell surface has only recently been revealed.We describe how PS is exposed in activated platelets and in apoptotic cells, and discuss the clearance of apoptotic cells.
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Objective:To observe effect of acupuncture combined with hypothermia therapy on MAPK/ERK pathway and apoptosis related factorsin rats suffered cerebral ischemia reperfusion and to explore underlying mechanisms.Methods:Middle cerebral artery ischemia model were established.Ninety SD rats were randomly assigned into a blank group,a control group,a model group,an acupuncture group,a mild hypothermia group,and an acupuncture with hypothermia group.After 72 h treatment,nervefunction defect scores were observed,and infarction area percent was detected by 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) staining;expressions of Bcl-2 and Bax were examined by immunohistochemistry;apoptotic cells were detected by TUNEL assay;and expression levels of phospho-mitogen-activated protein kinase(p-MEK2) and phospho-extracellular signal regulated kinase 1/2 (p-ERK1/2) in the rats' hippocampus ischemic side were determined by Western blot.Results:In the rats of the model group,the neural function defect scores,the infarction area percent,the expression level of Bax,and apoptotic cells increased,while the level of Bcl-2 decreased significantly.The level of p-MEK2 and p-ERK1/2 increased obviously compared with the blank and control groups (P＜0.05 or P＜0.01).After treatment with acupuncture and hypothermia,the neural function defect scores,infarction area percent,and the level ofBax,apoptotic cells and the levels of p-MEK2 and p-ERK1/2 were significantly decreased,while the level of Bcl-2 in the treatment group was significantly elevated (P＜0.05 or P＜0.01) compared with the model group.Compared with the acupuncture group or the hypothermia group,the neural function defect scores and the levels of p-MEK2 and p-ERK1/2 in the acupuncture combined with hypothermia group were significantly reduced (P＜0.05 or P＜0.01).Conclusion:Acupuncture and hypothermia therapy can improve cerebral function,and reduce the cerebral injury through down-regulation of Bax level,and up-regulation of Bcl-2 level,which is related to reducing the levels of p-MEK2 and p-ERK1/2.The therapeutic effects on cerebral ischemia reperfusion injury for combination of acupuncture with hypothermia are better than those with single application of acupuncture or hypothermia.
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Fenthion (FEN) is an organophosphorus pesticide known for its wide toxic manifestations. In this study, the effects of FEN were evaluated on the cerebrum and cerebellum oxidant/antioxidant status and histopathological disorders in the suckling rats. Pregnant rats were divided into two groups: control group received pure water, while FEN group received daily by their drinking water 551 ppm of FEN from the 14th day of pregnancy until day 14 after delivery. Acetylcholine esterase (AChE) activity was inhibited in both the cerebrum and cerebellum of suckling rats whose mothers were treated with FEN. The cerebrum and cerebellum oxidative damage was demonstrated by a significant increase of malondialdehyde (MDA), advanced oxidation protein product and glutathione (GSH) levels and disturbance in the antioxidant enzyme activities. A significant decline of non-protein thiol and vitamin C levels was also observed. These changes were confirmed by histopathological observations which were marked by pyknotic neurons in the cerebrum and apoptotic cells in the cerebellum of FEN-treated rats. In the cerebellum of FEN-treated rats, the most conspicuous damage was the absence of external granular layer, indicating growth retardation. These data suggested that exposure of pregnant and lactating rats to FEN induced oxidative stress and histopathological disorders in the cerebrum and cerebellum of their pups. Thus, the use of FEN must be under strict control, especially for pregnant and lactating mothers.
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Animals , Animals, Suckling , Antioxidants/metabolism , Brain/drug effects , Brain/metabolism , Brain/pathology , Female , Fenthion/toxicity , Insecticides/toxicity , Male , Oxidants/metabolism , Rats , Rats, WistarABSTRACT
Objective To observe the therapeutic effect of minimally invasive evacuation of intracerebral hematoma in dog model of cerebral hemorrhage by using Purdy score, serum levels of neuron-specific-enolase (NSE) and numbers of perihematomal apoptotic cells. Method Twenty dogs were selected to prepoxe the model of cerebral hemorrhage, and they were randomly divided( random number) into minimally invasive treatment group and control group. Minimally invasive procedures were performed to evacuate the hematoma in minimally invasive treatment group in 6 hours after the models were established. The dogs of control group only received medical treatment. Purdy score and serum levels of neuron-specific-enolase were determined on 1,3,5,7 days after the evacuation of the hemotoma and apoptotic cells were counted after the dogs were sacrificed at 7 days after operation. All the results were compared with control group. Purdy score and serum levels of neuron-specific-enolase were compaired with variance analysis of repeated measurement design and apoptotic cells was compared with variance analysis of factorial design,the difference of the two groups showed with q test. P <0.01 showed the difference was significant. Results The Purdy scores in minimally invasive treatment group were 6.3 ± 1.702, 5.8 ± 1. 685,4.2 ± 1.762 and 4.1 ± 1.875 on 1,3,5 and 7 day after evacuation of the hematoma, significant difference was observed as compared with the control group(8.9 ± 1.632, 8.6± 1.342, 7.8±1.335, 7.9±1.468, P <0.01).The serum levels of neuron-specific-enolase were 0.632 ± 0.077, 0.721±0.771, 0.549±0.124 and 0.430 ±0.136 respectively in minimally invasive treatment group, while in the control group were 0.934 ± 0. 064, 0. 997 ±0.075, 0.986 ± 0.042, 0.874 ± 0.165, significant differences in serum levels of neuron-specific-enolase were found between the two groups(P < 0.01). The perihematomal apoptotic cells in minimally invasive treatment group(37.4 cells) was decreased significantly as compared with the control group(88.6 cells), with P < 0.01.Conclusions Minimally invasive procedures for evacuation of intracerbral hematoma might significantly reduce the neurological deficit score and decrease the serum neuron-specific enolase levels and numbers of apeptotic neurons.
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BACKGROUND: There is a strong evidence that administration of anti-tumor drugs triggers apoptotic death of target cells. Therefore, quantitation of the 0early apoptotic cells could provide a very useful information for clinicians planning anti-tumor strategies. Therefore, we measured the amount of early apoptotic cells using annexin-FITC/PI dual fuorescence method by which early changes of apoptotic cell membrane could be detected. We also measured DNA content of apoptotic cells by PI single stain and performed DNA fragment assay simultaneously. METHODS: HL-60 cell line were cultured under 100, 200 ng/mL adriamycin for 12, 24, 36, 48 hours. Quantitation of the early apoptotic cells was done using flow cytometry with annexin-FITC and Propidium iodide (PI) dual fluorescence stain. And DNA content of the HL-60 cells was measured using PI single stain after fixing the cells. DNA ladder assay was also performed by agarose gel electrophoresis. RESULTS: The early apoptotic cells were 40.5% at adriamycin 100 ng/mL, after 24 hours culture and the secondary necrotic cells were 94.7% at adriamycin 200 ng/mL after 48 hours culture. There was a good correlation between annexin-PI stain and DNA content analysis. We could find DNA fragmentation on agarose gel electrophoresis. CONCLUSION: Quantitation of the early apoptotic cells using flow cytometry with annexin-PI dual fluorochrome stain and the DNA content analysis with PI single stain could be a good parameter for anti-apoptotic strategies.
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Humans , Cell Membrane , DNA , DNA Fragmentation , Doxorubicin , Electrophoresis, Agar Gel , Flow Cytometry , Fluorescence , HL-60 Cells , PropidiumABSTRACT
Objective To study the protective effects of estrogen on brain injured by cerebral ischemia-reperfusion in ovariectomized rats.Methods 30 d after bilateral ovariectomy,the benzestrofol 100 ?g/(kg?d)were intramusculari injected in to the models of ovariectomied rats for 14 d. Then the rat models of focal cerebral ischemia-reperfusion were made. The expressions of CD54 and TNF-? in brain tissue were detected by immunohistochemistry. The apoptotic cells were assayed by TUNEL,and the ultramicrostructural changes of neuron membrane was observed by electron microscope. Results Compared with the ischemia-reperfusion group and ovariectomized group,the expressions of CD54 and TNF-? of brain tissue in the estrogen group were significantly lower,and the apoptosis was reduced (all P
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Objective To investigate the effect of transfusion of allogeneic apoptotic splenocytes on immunological tolerance to pancreatic islets transplantation in rat. Method Recipient SD rats were rendered diabetic mellitus by a single intraperitoneal injection of streptozotocin (STZ). The apoptosis of donor Wistar rat splenocytes was induced by X-irradiation with electron linear accelerator. Pancreatic islets were isolated by intraductal collagenase P, and were purified by Ficoll-400 discontinuous density gradient after culturing for 1-2 days from donor Wistar rat. The diabetic SD rats were randomly divided into 4 groups, and respectively received infusion of Hanks solution, donor normal splenocytes, donor apoptotic splenocytes, and donor necrotic splenocytes via dorsal veins of penis, and then they received pancreatic islets from the same donor rat underneath their renal subcapsular space 7 days later. Mixed lymphocyte reaction (MLR) was used as immunological parameter of transplantation tolerance besides the observation of blood glucose level and allograft survival time. Islet graft failure was defined as the presence of a plasma glucose concentration of at least 11.0mmol/L on 2 successive days. Results The pre-infusion of donor apoptotic splenocytes significantly prolonged the survival time of allograft as shown by the median survival time (MST) of graft of 31days, and the longest survival time of 42 day, and it apparently decreased the rejection response in recipient SD rat in one-way mixed lymphocyte culture. Conclusion Transfusion of donor apoptotic splenocytes could induce immunological tolerance of allogenic islets transplantation in rat.
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Objective To investigate the morphological characteristics of the autophagic structures in macrophages after phagocytosis of apoptotic lymphocytes and to explore the effects of autophagy on clearance of the apoptotic cells by macrophages. Methods Apoptosis of lymphocytes was induced with cyclophosphamide.The morphological changes of macrophages phagocytizing the apoptotic cells were viewed with a scanning electron microscope.The structural features of the autophagosome precursors,autophagosomes and autophagolysosomes in macrophages were examined with a transmission electron microscope,and the cross-section areas of the autophagic structures were measured with an image analyzer.The autophagosomes of macrophages were labeled with monodansylcaolaverine(MDC) staining and quantitated using laser scanning confocal microscopy.Results Macrophages actively phagocytized the apoptotic lymphocytes,apoptotic nuclei,apoptotic bodies and other cell debris to form heterophagosomes.When compared with the control group,numbers of autophagic cells and autophagosomes in these cells increase in the group of macrophages that engulfed the apoptotic cells.In addition,the ratios of the cross-sectional areas of the autophagic structures to that of the cytoplasm of the macrophages were greater.There were also apoptotic bodies or other cell debris in many the autophagosomes,and these autophagosomes were large and near the cell membrane.Autophagosomes containing the whole apoptotic cell or apoptotic nucleus were not observed.Conclusion The autophagic abilities of macrophages were significantly enhanced when the cells removed the apoptotic lymphocytes.Autophagy also plays an important direct or indirect roles in clearance of the apoptotic lymphocytes by macrophages.