Angiogenesis, defined as the formation of new microvasculature from preexisting blood vessels and mature endothelial cells, plays a major role in wound healing and scar formation, and it is associated with inflammatory responses. Angiogenesis can occur in physiological conditions, such as during liver regeneration, and in pathological situations, such as during the progression of fibrosis to cirrhosis and also during tumor angiogenesis. Cellular cross-talk among liver sinusoidal endothelial cells (LSECs), hepatic stellate cells and hepatocytes is believed to play an important role in the angiogenesis process during both liver regeneration and development of cirrhosis. In addition to mature endothelial cells, bone marrow (BM)-derived circulating endothelial progenitor cells (EPCs) have been recently identified for their contribution to post-natal vasculogenesis/angiogenesis. In vivo, EPCs are mobilized into the peripheral blood in response to tissue ischemia or traumatic injury, migrate to the sites of injured endothelium and differentiate into mature endothelial cells. In our recent studies, we have explored the role of EPC-mediated angiogenesis in liver regeneration and/or cirrhosis. Results have demonstrated significantly increased endogenous levels of circulating EPCs in cirrhotic patients in comparison to the controls. Also, EPCs from cirrhotic patients have been observed to stimulate substantial angiogenesis by resident LSECs in vitro via paracrine factors such as vascular endothelial growth factor and platelet-derived growth factor. This review gives an overview of the angiogenesis process in liver regeneration and disease and discusses a new mechanism for intrahepatic angiogenesis mediated by BM-derived EPCs.

Background: Atherosclerosis is a chronic inflammation disease that is caused by the interaction between monocyte and endothelial injury in tunica intima. One of the major factor of atherosclerosis is dyslipidemia. Chronic dyslipidemia, especially hypercholesterolemia, can directly alter endothelial cell through reactive oxygen species (ROS) production that oxidizes low-density lipoprotein (LDL) to become oxidized LDL (Ox-LDL). Proinflammatory cytokines, the products of perivascular adipocyte tissue (PVAT), may draw macrophage. Macrophage then engulfs Ox-LDL and becomes foam cell within tunica intima. Lipoprotein-associated phospholipase A 2 (Lp-pLA 2) is an enzyme that cleaves Ox-LDL to become proatherosclerotic products. Darapladib, an Lp-pLA 2 inhibitor, is expected to inhibit atherosclerotic lesion progressivity. Aims and Objective: To know the effects of darapladib on Ox-LDL level, PVAT thickness, and foam cell number. Materials and Methods: This study used in vivo posttest controlled group design with two time series. Thirty male Sprague-Dawley rats divided into two group based on time series (8 weeks and 16 weeks). Each time serial was divided into three groups which were: standard diet group ;high-fat diet group; and dyslipidemia model with darapladib administration group with dose of 200 mg/200 g body weight (BW). The parameters that was measured in this study were lipid profile [total cholesterol, LDL/very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL)], Ox-LDL level, number of foam cells, and PVAT thickness. Result: Ox-LDL level and foam cell number decreased significantly (p = 0.000 and p = 0.005, respectively), while PVAT thickness did not show significant difference (p = 0.912). Conclusion: In this, study, it has been proven that darapladib decreases Ox-LDL levels and foam cell numbers but not in PVAT thickness, even though a decreasing pattern was observed histologically. Further study needed to know the optimum dosage of darapladib administration.

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Curcumin has been shown to regulate the expression of genes implicated in tumor cell proliferation, metastasis, chemotherapy resistance, and angiogenesis. Endothelial progenitor cells (EPCs) have been recently described in the peripheral blood as cells contributing to both physiological and pathological angiogenesis. In the current study, we evaluated the effect of curcumin on these angiogenic cells. EPCs were isolated, expanded, and characterized ex vivo. These cells were then treated with different concentrations of curcumin. The formation of EPC colonies in culture and their proliferation was analyzed by 5'-bromo-2'-deoxyuridine assays in absence and presence of curcumin. Further, the expression of two important cell cycle inhibitory proteins, p21 and p53, in the curcumin- and culture medium-treated cells without curcumin was evaluated by intracellular flow cytometry. The results showed that there was a significant decrease in the formation of EPC colonies in culture. EPC proliferation was significantly inhibited by curcumin in a dose-dependent manner. Flow cytometry analysis showed a twofold increase in the expression of both p21 and p53 in curcumin-treated cells as compared to the medium-treated cells, suggesting that curcumin inhibits EPC growth by mainly inhibiting the G1 to S phase transition in the cell cycle. It would be further worthwhile to study the effect of curcumin on EPC-mediated angiogenic activity.

Metabolic inflammation (low-grade inflammation) remains an etiopathogenic key factor in the development of metabolic syndrome. Nuclear Factor Kappa Beta (NF-κβ) is a transcription regulator of genes having a role in immunity, the inflammatory response which can be associated with obesity-related pathological conditions like nonalcoholic fatty liver (NAFLD). Various stimuli, such as metabolic stress (hyperglycemia, ROS, fat metabolism) and proinflammatory cytokines (TNF-α, IL-6, IL-1β) could activate NF-κβ. This study was aimed to investigate the underlying molecular mechanisms of NAFLD in rats fed a modified AIN-93M HFHF (High Fat High Fructose) diet. The design of this study was experimental post-test only controlled group design. Thirty male Sprague Dawley rats were distributed into 2 treatment groups by a completely randomized design (CRD) technique. The sacrifice was performed after 17 weeks of treatment. NF-κβ expression was assessed by an immunohistochemical method (IRS score). The results showed there were significant differences in feed intake and energy intake between groups P1 and P2 (p = 0,000, p = 0,000). The average NF-κβ expression in the P2 group was significantly higher (p = 0.000) compared to the control group (P1). The correlation test between dietary intake and NF-κβ expression proved that there was a positive correlation between energy, carbohydrate and fat intake on NF-κβ expression (p = 0.001, 0.000, 0.046). However, there was a negative relationship between protein intake and NF-κβ expression (p = 0.000). This study concluded the modified AIN-93M HFHF diet increased NF-κβ expression in the liver tissue of male Sprague Dawley rats.

Lead is one of the pollutants widely spread in the environment because it is not easily decomposed. Lead can affect system functions such as the ovary and endometrium. Lead can trigger oxidative stress by reducing antioxidant enzymes and increasing Reactive Oxygen Species (ROS). Lead can also reduce Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels by disturbing the hypothalamus. Chitosan is an antioxidant compound that can reduce the toxic effects of lead. The purpose of this study was to study the effects of chitosan administration on the diameter of antral follicles, the number of endometrial arterioles, and the thickness of endometrial rats after lead acetate exposure. This study was an experimental laboratory using a posttest-only control group design approach applied on 25 female rats aged 8 weeks old, body weight 125-175 grams. Lead and chitosan were given orally with a sonde. There were 5 groups, namely, negative control group (without any treatment), positive control group (lead 175mg/kg/BW), treatment group 1 (lead 175mg/kg/BW + chitosan 16mg/kg/BW, treatment group 2 (lead 175mg/kg/BW + chitosan 32mg/kg/BW), and treatment group 3 (lead 175mg/kg/BW + chitosan 64mg/kg/BW) for 30 days. The rats were sacrificed at proestrus phase, which was proven from vaginal swab. Observations were carried out using the Hematoxylin Eosin (HE) staining method. The observations were analyzed using One Way ANOVA and followed by Least Significant Differences (LSD) test. The results showed significant results (p-value <0.05). Chitosan can increase the diameter of the antral follicle, increase the number of endometrial arterioles, and increase the thickness of endometrial rats exposed by lead acetate.

Kanker prostat yang didominasi oleh adenokarsinoma prostat adalah salah satu keganasan yang sering didapatkan pada laki-laki. Studi terkini menyebutkan bahwa estrogen receptor berhubungan dengan kanker prostat. namun masih didapatkan kontroversi hubungan reseptor ini dengan kanker prostat dan prognosis kanker prostat. Sejauh ini, di Indonesia belum ada penelitian yang dilakukan untuk mencari hubungan ER dengan prognosis pasien kanker prostat. Penelitian ini bertujuan untuk membuktikan adanya hubungan antara ekspresi ER dengan skor Gleason, derajat diferensiasi, dan prognostic grade group pasien adenokarsinoma prostat. Desain penelitian adalah observasional analitik, menggunakan 31 sampel adenokarsinoma prostat berdasarkan perhitungan statistik. Ekspresi ER diukur pada kelompok spesimen jaringan adenokarsinoma prostat, yang kemudian dilakukan uji korelasi Spearman terhadap skor Gleason, derajat diferensiasi serta prognostic grade group (PGG). Pada penelitian ini didapatkan nilai p > 0,05 pada uji korelasi spearman antara ekspresi reseptor estrogen terhadap skor Gleason (p = 0,601), derajat diferensiasi (p = 0,754 ) dan prognostic grade group (p = 0,596) pada adenokarsinoma prostat. Hasil penelitian juga menunjukkan kecenderungan rerata ekspresi reseptor estrogen pada kelompok poorly differentiated adenokarsinoma prostat lebih tinggi dibandingkan kelompok moderately differentiated. Namun, pada prognostic grade group terdapat kecenderungan rerata ekspresi reseptor estrogen meningkat pada PGG yang lebih tinggi. Kesimpulannya, tidak didapatkan korelasi yang bermakna antara ekspresi reseptor estrogen dengan skor Gleason, derajat diferensiasi, dan prognostic grade group pada adenokarsinoma prostat. Disarankan untuk menentukan prognosis kanker prostat dari berbagai aspek, tidak hanya dari skor Gleason, derajat diferensiasi, dan prognostic grade group, tetapi juga mempertimbangkan stadium TNM dan kadar prostate spesific antigen (PSA).

Sebagian besar karsinoma kolorektal adalah adenokarsinoma, dan lebih dari 95% karsinoma kolorektal diawali oleh lesi prekursor yaitu adenoma. Risiko suatu adenoma berubah menjadi suatu karsinoma akan lebih tinggi pada adenoma dengan ukuran lebih dari 1 cm, tipe villous, dan disertai displasia high grade. Telah diketahui bahwa grading dan stadium merupakan faktor prognostik penting baik pada adenoma maupun adenokarsinoma. Perkembangan adenoma menjadi adenokarsinoma melibatkan peran banyak gen dan protein, salah satunya cyclin D1 yang berperan meningkatkan proliferasi sel, angiogenesis dan invasi sel. Penelitian ini bertujuan untuk mengetahui perbedaan ekspresi cyclin D1 antara adenoma dan adenokarsinoma kolorektal, serta hubungannya dengan grading dan stadium tumor. Lalu, ditentukan 30 sampel untuk masing-masing adenoma dan adenokarsinoma yang diambil dari Instalasi Patologi Anatomi RS. dr. Saiful Anwar Malang. Keseluruhan sampel dilakukan pulasan imunohistokimia dengan antibodi cyclin D1 kemudian dihitung persentase ekspresinya, dan dianalisis hubungan antara cyclin D1 tersebut dengan grading pada adenoma dan grading serta stadium pada adenokarsinoma. Hasil penelitian menunjukkan terdapat perbedaan ekspresi cyclin D1 yang bermakna antara kelompok adenoma dan adenokarsinoma dengan p < 0,01. Tidak terdapat hubungan yang bermakna antara ekspresi cyclin D1 dengan grading adenoma serta grading dan stadium adenokarsinoma (p > 0,05). Kesimpulan penelitian ini adalah ekspresi cyclin D1 dapat digunakan untuk membedakan antara adenoma dan adenokarsinoma, tetapi ekspresi tersebut tidak berhubungan dengan grading dan stadium tumor.