Doxorubicin induced immune abnormalities and inflammatory responses via HMGB1, HIF1-α and VEGF pathway in progressive of cardiovascular damage.

Background: Doxorubicin (DOX) is a commonly used treatment for cancer and the mechanism of DOX-induced cardiomyocyte damage in cardiovascular disease is not fully understood. High-mobility group box 1 (HMGB1), strong induce proinflammatory cytokines via damage associated molecular pattern (DAMP) which its interaction with the receptor of advanced glycation end products (RAGE), that affect cytokine release, and angiogenesis via the role of HMBG1, HIF-1α and VEGF as an important regulator in these cardiac failure processes. Hypoxia-inducible factor-1α (HIF-1α) is plays an important role in the cellular response to systemic oxygen levels of cells and VEGF is an angiogenic factor and can stimulate cellular responses on the surface of endothelial cells will be described. Objective: The aim of this article is to comprehensively review the role of HMGB1, HIF-1α, and VEGF in DOX-induced Cardiovascular Disease and its molecular mechanisms. Methods: The data in this study were collect by search the keyword combinations of medical subject headings (MeSH) of "HMGB1", "HIF-1 α", "VEGF", "DOX" and "Cardiovascular disease" and relevant reference lists were manually searched in PubMed, EMBASE and Scopus database. All relevant articles in data base above were included and narratively discussed in this review article. Results: Several articles were revealed that molecular mechanisms of the DOX in cardiomyocyte damage and related to HMGB1, HIF-1α and VEGF and may potential treatment and prevention to cardiovascular disease in DOX intervention. Conclusion: HMGB1, HIF-1α and VEGF has a pivotal regulator in DOX-induce cardiomyocyte damage and predominantly acts through different pathways. The role of HMGB1 in DOX-induced myocardial damage suggests that HMGB1 is a mediator of DOX-induced damage. In addition, DOX can inhibit HIF-1α activity where DOX can decrease HIF-1α expression and HIF-1α is also responsible for upregulation of several angiogenic factors, including VEGF. VEGF plays an important role in angiogenesis and anti-angiogenesis both in vitro and in vivo and reduces the side effects of DOX markedly. In addition, the administration of anti-angiogenesis will show an inhibitory effect on angiogenesis mediated by the VEGF signaling pathway and triggered by DOX in cells.

Drug utilization study and cost analysis of adult ß-thalassemia major patient therapy at Dr. Soetomo General Hospital Surabaya.

OBJECTIVES: The main therapy of ß-thalassemia major are blood transfusion and iron chelation drugs. However, those therapies also have some adverse effects and problems such as iron overload, transfusion reactions, nutritional deficiencies, and patient compliance problems. Those arising problems also have an impact on therapy cost. Hence, this study was designed to analyze drug utilization study and cost of therapy in ß-thalassemia major adult patients at Dr. Soetomo General Hospital Surabaya. METHODS: This research was conducted in descriptive observational-retrospective design using secondary data obtained from patient's medical records and billing registrations from January 1-December 31, 2019. RESULTS: There were 18 patients out of 233 patients that were analyzed. Deferasirox was the most administered drug with doses between 500 mg/day-1,500 mg/day while deferiprone was ranged between 1,500 and 4,500 mg/day. Patients also received transfusion reaction drugs with dexamethasone injection 5 mg/ml which was administered the most. The most administered supplement was folic acid 1 mg. Patients had an increase in serum ferritin due to low compliance. Deferasirox had the most adherence number of patients with decrease of serum ferritin. The two highest costs of direct medical components were top-up medicines and consumable medical supplies. Overall, the hospital gained profit from national health insurance claims. CONCLUSIONS: The most administered chelating agent was deferasirox. Deferasirox also had the most adherence number of patients with decreased number of serum ferritin. However, deferasirox also yielded the highest cost. Yet, overall, the hospital gained profit from national health insurance claims.

Serum vitamin D receptor and High Mobility Group Box-1 (HMGB1) levels in HIV-infected patients with different immunodeficiency status: A cross-sectional study.

BACKGROUND: HIV-AIDS patients typically have hypovitaminosis D. Vitamin D is a key mediator in inflammatory and infectious diseases, which VDR mediates its biological effect. High-mobility group box 1 protein (HMGB1) modulates HIV-1 replication in vitro. Vitamin D played a role in inhibiting HMGB1 secretion in the animal study. OBJECTIVES: This study aimed to examine differences and correlation of vitamin D receptor and HMGB1 protein levels in HIV patients with mild and severe immunodeficiency and healthy control participants. METHODS: This study using a cross-sectional design conducted at Volunteer Counseling and Testing (VCT) Clinic in Mataram, West Nusa Tenggara, Indonesia, from January to June 2020. Three groups of study participants were classified as HIV patients with severe immune deficiency (SID), HIV patients with mild immune deficiency (MID), and healthy controls (HC). RESULTS: Mean level of vitamin D receptor in SID HIV group was 25.89 ± 3.95 ng/ml, lower than those in MID-HIV group; 33.72 ± 1.69 ng/ml and in HC group; 50.65 ± 3.64 ng/ml. Mean levels of HMGB1 protein in the SID HIV group were 3119.81 ± 292.38 pg/ml higher than those in the MID HIV group 1553.55 ± 231.08 pg/ml and HC 680.82 ± 365.51 pg/ml. There was a significant and strong negative correlation (r = -0.932) between vitamin D receptor and HMGB1 levels (p < 0.01). CONCLUSIONS: Strong negative correlation between VDR and HMGB1 in different immunodeficiency statuses suggesting an important role of vitamin D in inflammation control in HIV infection. However, it needs to be confirmed in a further prospective study.

Evaluation to the chemotherapy use in patients with diffuse large B-cell lymphoma.

Background Non-Hodgkin lymphoma (NHL) is a large group of primary malignancies of solid lymphoid tissue. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL. DLBCL has an aggressive natural history but responds well to chemotherapy. The objective of this study was to review the use of chemotherapy, identify its side effects, and examine the response to chemotherapy in patients with NHL at Dr. Soetomo General Hospital. Methods This study was a retrospective observational study using secondary data obtained from patients' medical records from 2016 to 2018. Demographic data (age, sex), clinical characteristics, chemotherapy regimens, side effects of chemotherapy, and response to chemotherapy were recorded. Results Results revealed that of the 43 patients (age ranged from 21 to 80 years) who were included in this study, the prevalence of DLBCL was higher in male patients (74%) and about 44% patients were at stage III. R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine/oncovin, prednisone) (53%) was the most used chemotherapy regimen in this study. A total of 65% of patients showed good responses and 35% showed no response to the therapy. The most common side effect was myelosuppression, including 25% and 8% of the patients having anemia and leukopenia, respectively. Conclusions R-CHOP is the most used regimen. Most of patients with NHL have a complete response and the predominant side effect is anemia.