The life expectancy for pancreatic cancer patients has seen no substantial changes in the last 40 years as very few and mostly just palliative treatments are available. As the five years survival rate remains around 5%, the identification of novel pharmacological targets and development of new therapeutic strategies are urgently needed. Here we demonstrate that inhibition of the G protein-coupled receptor GPR55, using genetic and pharmacological approaches, reduces pancreatic cancer cell growth in vitro and in vivo and we propose that this may represent a novel strategy to inhibit pancreatic ductal adenocarcinoma (PDAC) progression. Specifically, we show that genetic ablation of Gpr55 in the KRAS/TP53/Pdx1-Cre (KPC) mouse model of PDAC significantly prolonged survival. Importantly, KPC mice treated with a combination of the GPR55 antagonist Cannabidiol (CBD) and gemcitabine (GEM, one of the most used drugs to treat PDAC), survived nearly three times longer compared to mice treated with vehicle or GEM alone. Mechanistically, knockdown or pharmacologic inhibition of GPR55 reduced anchorage-dependent and independent growth, cell cycle progression, activation of mitogen-activated protein kinase (MAPK) signalling and protein levels of ribonucleotide reductases in PDAC cells. Consistent with this, genetic ablation of Gpr55 reduced proliferation of tumour cells, MAPK signalling and ribonucleotide reductase M1 levels in KPC mice. Combination of CBD and GEM inhibited tumour cell proliferation in KPC mice and it opposed mechanisms involved in development of resistance to GEM in vitro and in vivo. Finally, we demonstrate that the tumour suppressor p53 regulates GPR55 protein expression through modulation of the microRNA miR34b-3p. Our results demonstrate the important role played by GPR55 downstream of p53 in PDAC progression. Moreover our data indicate that combination of CBD and GEM, both currently approved for medical use, might be tested in clinical trials as a novel promising treatment to improve PDAC patients' outcome.

Metabolism is a chemical process used by cells to transform food-derived nutrients, such as proteins, carbohydrates and fats, into chemical and thermal energy. Whenever an alteration of this process occurs, the chemical balance within the cells is impaired and this can affect their growth and response to the environment, leading to the development of a metabolic disease. Metabolic syndrome, a cluster of several metabolic risk factors such as abdominal obesity, insulin resistance, high cholesterol and high blood pressure, and atherogenic dyslipidaemia, is increasingly common in modern society. Metabolic syndrome, as well as other diseases, such as diabetes, obesity, hyperlipidaemia and hypertension, are associated with abnormal lipid metabolism. Cellular lipids are the major component of cell membranes; they represent also a valuable source of energy and therefore play a crucial role for both cellular and physiological energy homeostasis. In this review, we will focus on the physiological and pathophysiological roles of the lysophospholipid mediator lysophosphatidylinositol (LPI) and its receptor G-protein coupled receptor 55 (GPR55) in metabolic diseases. LPI is a bioactive lipid generated by phospholipase A (PLA) family of lipases which is believed to play an important role in several diseases. Indeed LPI can affect various functions such as cell growth, differentiation and motility in a number of cell-types. Recently published data suggest that LPI plays an important role in different physiological and pathological contexts, including a role in metabolism and glucose homeostasis.

Proses pembelajaran ataupun kegiatan belajar-mengajar tidak bisa lepas dari keberadaan guru. Tanpa adanya guru pembelajaran akan sulit dilakukan, apalagi dalam rangka pelaksanaan pendidikan formal, guru menjadi pihak yang sangat vital. Guru memiliki peran yang paling aktif dalam pelaksanaan pendidikan demi mencapai tujuan pendidikan yang hendak dicapai. Guru melaksanakan pendidikan melalui kegiatan pembelajaran dengan mengajar peserta didik atau siswa. Pendidikan jasmani mempunyai peran yang sangat penting terutama dalam meningkatkan kualitas sumber daya manusia yang dilakukan dengan berbagai aktivitas jasmani, sehingga diperoleh kesehatan dan kebugaran tubuh. Melalui pendidikan jasmani, baik aspek fisik (kualitas fisik) maupun aspek nonfisik (kualitas non-fisik) yang menyangkut kemampuan kerja, berfikir dan keterampilan dapat teratasi. Oleh sebab itu, keduanya harus saling terkait dan mendukung, sehingga peningkatan kualitas sumber daya manusia yang tangguh dapat tercapai.Kata Kunci: Peran Guru, Pendidikan Jasmani dan Karakter Peserta didik.

In Indonesian national system of education, Islamic religious education is compulsory for all levels of formal education. Taking into account such a position, Islamic religious education is potentially strategic in responding to some of the main issues in religious life. One issue examined in this paper is radicalism that continues to overshadow the dynamics of religious life in In- donesia. Although numerous attempts (mainly security approach) to eradi- cate radicalism have been taken, radicalism is still a prominent problem in Indonesia. This paper argues that Islamic religious education should be em- powered in order to reduce the spread of radicalism. In order to bring these ideas into reality, this paper further offers Living Values E education (LVE) as a theoretical framework to develop Islamic religious education which is com- patible with this goal. Pendidikan agama Islam dalam sistem pendidikan nasional di Indonesia merupakan salah satu materi yang wajib diajarkan dalam institusi pendidikan formal mulai dari jenjang pendidikan dasar sampai ke jenjang pendidikan tinggi. Dengan mempertimbangkan posisinya yang demikian, pendidikan agama Is- lam memiliki potensi strategis untuk merespons beberapa persoalan utamanya dalam kehidupan agama. Salah satu persoalan yang hendak dikaji dalam tulisan ini adalah radikalisme yang terus membayangi kehidupan umat beragama di Indonesia. Meskipun telah dirancang berbagai upaya untuk membendung radikalisme terutama dengan menggunakan pendekatan keamanan, radikalisme ternyata masih eksis di Indonesia. Tulisan ini menawarkan pendidikan agama Islam sebagai salah satu institusi pendidikan yang perlu diberdayakan untuk membendung arus radikalisme. Untuk mewujudkan pemikiran tersebut, tulisan ini selanjutnya menawarkan living values education (LVE) sebagai suatu kerangka teoritik untuk mengembangkan pendidikan agama Islam.