The role of peroxisomes in oxidative stress

Peroxisomes are one of the main sites in the cell where oxygen free radicals are both generated and scavenged. The balance between these two processes is believed to be of great importance for proper functioning of cells and has been implicated in aging and carcinogenesis. To gain more insight in the functioning of the peroxisome, we developed a new method to measure the biophysical properties of these organelles in the living cell. To achieve this we made use of small fluorescently labelled polypeptides with a peroxisomal targeting signal of type I. Using such a probe, we determined the peroxisomal matrix is alkaline and that the peroxisomal membrane is impermeable to protons under physiological conditions. Oxidative stress deriving from peroxisomal b-oxidation is to be detoxified by a set of anti-oxidant enzymes. In this thesis I show that next to the well known enzymes catalase and MnSOD, the sterol carrier protein 2 (SCP2) plays a role in the protection against oxidative stress. We show that mice lacking this protein have higher basal levels of lipid-peroxidation in the liver and develop liver tumours. In a model I propose that this peroxisomal protein shields poly-unsaturated fatty acyl-CoA esters from free radicals that are present in the organellar matrix. The regulation of anti-oxidant activity in the cell has been a matter of study. We show that MnSOD is directly regulated by the daf-16 like Forkhead transcription factors. Forkhead transcription factors are negatively regulated by phosphatidyl-inositol-3-OH-kinase (PI-3-kinase) through phosphokinase B (PKB). Catalase and SCP2 are also increased upon activation of the Forkheads, but until now we do not know whether this reflects a direct regulation. A model is proposed for the regulation of anti-oxidant capacity of the cell in relation to metabolism

Pengaruh Kualitas Tidur Terhadap Kejadian Kejang Pada Pasien Epilepsi

Background: Epilepsy is the most common neurological disorder. In developing countries, the incidence of epilepsy is higher than in developed countries. The incidence of seizures in epilepsy can be reduced with regular treatment, but not a few who experience recurrent seizures, this can be influenced by several factors other than irregular treatment. One of the factors is the influence of sleep quality. Objective: To find out more about the effect of sleep quality on the incidence of seizures in epilepsy. Methods: Using literature studies from several national and international journals. Conclusion: There is an effect of sleep quality on the incidence of seizures in epileptic patients.Latar Belakang : Epilepsi adalah kondisi gangguan neurologik yang paling sering ditemui. Pada negara berkembang, insidensi epilepsi lebih tinggi dari negara maju. Kejadian kejang pada epilepsi dapat dikurangi dengan pengobatan yang teratur akan tetapi tidak sedikit juga yang mengalami kejadian kejang berulang, hal ini dapat dipengaruhi beberapa faktor selain pengobatan yang tidak teratur. Salah satu faktornya adalah pengaruh dari kualitas tidur. Tujuan : Mengetahui lebih lanjut pengaruh kualitas tidur terhadap kejadian kejang pada epilepsy.  Metode : Menggunakan studi literatur dari beberapa jurnal nasional dan internasional. Kesimpulan : Terdapat pengaruh kualitas tidur terhadap kejadian kejang pada pasien epilepsi

Release of Mps1 from kinetochores is crucial for timely anaphase onset

Mps1 regulates its own turnover at kinetochores to ensure mitotic checkpoint silencing in metaphase

PENINGKATAN PENGETAHUAN KESEHATAN KULIT PADA SISWA SMA METHODIST JAKARTA UTARA MELALUI KEGIATAN PROMOSI KESEHATAN

Kegiatan promosi kesehatan kulit pada siswa SMA Methodist, Jakarta Utara yang dilaksanakan pada tanggal 20 Juli 2023 berhasil meningkatkan pengetahuan siswa tentang kesehatan kulit. Hal ini terlihat dari peningkatan nilai rata-rata pengetahuan siswa dari 4,42 menjadi 9,49. Kegiatan ini juga mendapatkan umpan balik yang sangat baik dari peserta. Secara keseluruhan, 95,16% peserta menyatakan puas dengan kegiatan ini. Kegiatan ini menggunakan metode ceramah, workshop, dan pemberian flyer. Ceramah disampaikan oleh dosen farmasi dari Universitas Katolik Indonesia Atma Jaya, sedangkan workshop pembuatan masker peel-off dipandu oleh mahasiswa/i program studi Farmasi, FKIK Universitas Katolik Indonesia Atma Jaya. Flyer kesehatan kulit yang disusun secara sistematis, singkat, dan padat juga diberikan kepada peserta. Selain itu, kegiatan ini juga menghasilkan satu series video edukasi dengan topik ‘Perawatan Kulit Wajah’ yang terdiri dari tiga video pendek berdurasi tidak lebih dari 4 menit. Ketiga video ini diunggah di platform media sosial Instagram agar dapat menjangkau masyarakat yang lebih luas tidak hanya peserta seminar dan workshop. Kegiatan promosi kesehatan kulit ini diharapkan dapat meningkatkan kesadaran masyarakat, khususnya remaja, tentang pentingnya perawatan kulit yang aman dan sesuai dengan kebutuhan kulit.&nbsp

Роль совершенствования бухгалтерского учета в управлении производственными запасами

Целью проведения исследования является обоснование направлений повышения эффективности использования материальных производственных запасов на предприятии в условиях рыночной экономики

Bcl-xL gain of function and p19ARF loss of function cooperate oncogenically with Myc in vivo by distinct mechanisms

SummaryOverexpression of Bcl-xL, loss of p19ARF, and loss of p53 all accelerate Myc oncogenesis. All three lesions are implicated in suppressing Myc-induced apoptosis, suggesting that this is a common mechanism by which they synergize with Myc. However, using an acutely switchable model of Myc-induced tumorigenesis, we demonstrate that each lesion cooperates with Myc in vivo by a distinct mechanism. While Bcl-xL blocks Myc-induced apoptosis, inactivation of p19ARF enhances it. However, this increase in apoptosis is matched by increased Myc-induced proliferation. p53 inactivation shares features of both lesions, partially suppressing apoptosis while augmenting proliferation. Bcl-xL and p19ARF loss together synergize to further accelerate Myc oncogenesis. Thus, differing lesions cooperate oncogenically with Myc by discrete mechanisms that can themselves synergize with each other

The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help

Germinal center (GC) B cells cycle between two states, the light zone (LZ) and the dark zone (DZ), and in the latter they proliferate and hypermutate their immunoglobulin genes. How this functional transition takes place is still controversial. In this study, we demonstrate that ablation of Foxo1 after GC development led to the loss of the DZ GC B cells and disruption of the GC architecture, which is consistent with recent studies. Mechanistically, even upon provision of adequate T cell help, Foxo1-deficient GC B cells showed less proliferative expansion than controls. Moreover, we found that the transcription factor BATF was transiently induced in LZ GC B cells in a Foxo1-dependent manner and that deletion of BATF similarly led to GC disruption. Thus, our results are consistent with a model where the switch from the LZ to the DZ is triggered after receipt of T cell help, and suggest that Foxo1-mediated BATF up-regulation is at least partly involved in this switch

Возможность прогнозирования клеточного типа увеальных меланом без использования инвазивных методов диагностики

Резюме. С помощью дискриминантного анализа установлена возможность определения клеточного типа меланомы увеального тракта в процессе проведения комбинированного (фотокоагуляция + брахитерапия) лечения. Разработана высокозначимая (l = 0,08; р = 0,002) дискриминантная модель, включающая ряд клинических (степень пигментации, пол, скорость роста меланомы) и иммунологических (количество Т- и В-лимфоцитов, процент Т-хелперов и др.) показателей. Особое место в модели занимают признаки, в наибольшей степени отражающие биологические особенности увеальных меланом различного клеточного состава, а именно — скорость изменения размера опухоли в процессе лечения и изменение показателей клеточного иммунитета. Ключевые слова: увеальная меланома, клеточный тип, клинико-морфологические, иммунологические показатели, дискриминантный анализ.Summary. Application of the discriminant analysis shows that it is possible to define the cell type of melanoma of uveal tract of the eye in the process of combined (photocoagulation + brachytherapy) treatment. A highly reliable (l= 0,08; р = 0,002) discriminant model was elaborated, involving a number of both clinical (pigmentation level, gender, melanoma growth rate) and immunological (number of T and B lymphocytes, T helper rate, etc.) indicators. In this model, especially important are those traits that most pronouncedly reflect the biological peculiarities of uveal melanomas of various cellular compositions, namely — the pace of tumor size growth in the process of treatment and changes in cell immunity indicators. Key Words: uveal melanoma, cell type, clinical and morphological, immunological indicators, discriminant analysis

DNA damage and oxidant stress activate p53 through differential upstream signaling pathways

Stabilization and activation of the p53 tumor suppressor are triggered in response to various cellular stresses, including DNA damaging agents and elevated Reactive Oxygen Species (ROS) like H2O2. When cells are exposed to exogenously added H2O2, ATR/CHK1 and ATM/CHK2 dependent DNA damage signaling is switched on, suggesting that H2O2 induces both single and double strand breaks. These collective observations have resulted in the widely accepted model that oxidizing conditions lead to DNA damage that subsequently mediates a p53-dependent response like cell cycle arrest and apoptosis. However, H2O2 also induces signaling through stress-activated kinases (SAPK, e.g., JNK and p38 MAPK) that can activate p53. Here we dissect to what extent these pathways contribute to functional activation of p53 in response to oxidizing conditions. Collectively, our data suggest that p53 can be activated both by SAPK signaling and the DDR independently of each other, and which of these pathways is activated depends on the type of oxidant used. This implies that it could in principle be possible to modulate oxidative signaling to stimulate p53 without inducing collateral DNA damage, thereby limiting mutation accumulation in both healthy and tumor tissues