Circulation microRNA expression profiles in patients with complete responses to chemoradiotherapy in nasopharyngeal carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is endemic cancer in Southeast Asia with a relatively poor prognosis. Chemoradiotherapy is a primary treatment that advantages certain patients, particularly in the early stages. New predictive and prognostic biomarkers are required to guide and select the best treatment. Aims: To evaluate the circulation expression profile of microRNAs (miRNAs) associated with responses to chemoradiotherapy in nasopharyngeal carcinoma. Methods: Peripheral blood from 17 patients was collected before and after chemotherapy and radiotherapy. Differential expression circulating miRNAs were analyzed using microRNA Cancer Panels and were compared among patients with complete responses. Differential expression analysis using GenEx 7 Multid, statistic represented by GraphPad Prism 9. Alterations mechanism signaling pathways and biological function using IPA (Ingenuity Pathways Analysis). Results: Using microRNAs Cancer Plate consisting of 116 miRNAs, we identified ten circulating miRNAs that were differentially expressed in NPC patients after chemoradiotherapy. Unsupervised clustering and confirmation using qRT-PCR showed that miR-483-5p, miR-584-5p, miR-122-5p, miR-7-5p, miR-150-5p were overexpressed and miRNA are miR-421, miR-133a-3p, miR-18a-5p, miR-106b-3p, miR-339-5p were significantly downregulated after chemoradiotherapy (p < 0.0001). In addition, ROC analysis through AUC (Area Under Curve) with 99% confidence interval (CI) p value < 0.0001. Gene enrichment analysis of microRNAs and the targeted proteins revealed that the main involved pathways for chemoradiotherapy in NPC were cell death and survival signaling pathways. Conclusion: qPCR profiling in circulating blood compared before and after chemoradiotherapy in nasopharyngeal carcinoma can identify pathways involved in treatment responses. miR-483-5p, miR-584-5p, miR-122-5p, miR-7-5p, miR-150-5p, miR-421, miR-133a-3p, miR-18a-5p, miR-106b-3p, miR-339-5p are differentially regulated after chemoradiotherapy in NPC.

Anticancer Activity of Pasak Bumi Root Extract (Eurycoma longifolia Jack) on Raji Cells.

<b>Background and Objective:</b> The use of the roots of the pasak bumi (<i>E. longifolia</i> Jack) to treat cancer has been studied widely, however, the scientific basis of these plants used as an anticancer drug is widely unknown. The purpose of this study was to examine the anticancer activity of ethyl acetate and non-ethyl acetate fractions of pasak bumi roots in Raji cells. <b>Materials and Methods:</b> The cytotoxicity test is using the direct cell count method with trypan blue staining. The growth inhibition is using doubling time analysis of Raji cells. Observation of the apoptotic events of Raji cells used ethidium bromide staining, while observing the expression of p53 protein in Raji cells was done by immunohistochemical staining. <b>Results:</b> The results of the cytotoxicity and doubling time test showed that the activity of the non-ethyl acetate fraction was greater than that of the roots of pasak bumi. The lower concentration of non-ethyl acetate fraction of pasak bumi roots was able to delay the multiplication time of Raji cells which was greater than that of ethyl acetate. The results of the cytotoxicity and doubling time test showed that the activity of the non-ethyl acetate fraction was greater than that of the roots of pasak bumi. <b>Conclusion:</b> It can be concluded that the ethyl acetate and non-ethyl acetate fractions of the roots of pasak bumi have cytotoxic and antiproliferative activity on Raji cells, however they cannot induce apoptosis in Raji cells. The death of Raji cells is through the mechanism of inhibiting Raji cell proliferation as evidenced by an increase in p53 protein expression.

Effect of Papaya Leaves (Carica papaya L.) Extract on Immune Response (TLR-7, TLR-9) and Inflammation (COX-2) in Rats Induces DMBA (7,12-Dimethylbenz[a]antrasen).

BACKGROUND AND OBJECTIVE: TLR is known to regulate the immune system in cancer. TLR-7 and TLR-9 can enhance the antitumor immune system in many types of solid tumors. Cyclooxygenase-2 (COX-2) is a biomarker of inflammation. This study aimed to investigate the effect of papaya leaves extract on immune response (TLR 7, TLR 9) and inflammation (COX-2) in rats induced DMBA. MATERIALS AND METHODS: This experimental study used Sprague dawley female rats of age more less 50 days. Rats were divided into 4 groups: Negative Control (NC), Positive Control (PC), Cancer Drug Doxorubicin (DOXO) and Papaya Leaves Extract (PLE). The study was conducted for 13 weeks. DMBA induction performed for 5 weeks with administration of 2 times per week. RESULTS: the expression of TLR-7 of PLE and DOXO was higher than PC groups significantly different (p<0.05). The expression of TLR-9 of PLE was higher than NC, PC and DOXO groups but not significantly different (p>0.05) while the expression of COX-2 of PLE and DOXO groups was lower than NC and PC groups but not significantly different (p>0.05). CONCLUSION: It can be concluded that papaya leaves extract can improve the immune system and reduce inflammation. It shows that papaya leaves extract has potent as anti-cancer.

Anti-proliferation and Apoptosis Induction of Aqueous Leaf Extract of Carica papaya L. on Human Breast Cancer Cells MCF-7.

BACKGROUND AND OBJECTIVE: Breast cancer is the most frequently diagnosed cancer in women. Chemotherapy is the main method of breast cancer treatment but there are side effects. Carica papaya leaves is vegetable foods consumed by most people of Indonesia have potential as anticancer. The aim of this study was to investigate anti-proliferative and apoptotic induced effect of aqueous papaya leaves extracts on human breast cancer cell lines MCF-7. MATERIALS AND METHODS: Inhibitory on cell proliferation was measured by MTT assay while apoptosis induction was measured using Annexin V. RESULTS: The results showed that papaya leaf can inhibit the proliferation of human breast cancer cells MCF-7 with IC50 in 1319.25 µg mL-1. The IC50 values of papaya leaf extract was higher than the IC50 value quercetin and doxorubicin. Papaya leaf extract can also induce apoptosis of breast cancer cells MCF-7 about 22.54% for concentration 659.63 µg mL-1 and about 20.73% for concentration 329.81 µg mL-1. The percentage of cell apoptosis of papaya leaf extract lower than doxorubicin but higher than quercetin. CONCLUSION: This study indicated that papaya leaf extract have potential as anticancer through mechanism anti-proliferation and apoptosis induction.

Evolutionary dynamics of SARS-CoV-2 circulating in Yogyakarta and Central Java, Indonesia: sequence analysis covering furin cleavage site (FCS) region of the spike protein / Dinámica evolutiva del SARS-CoV-2 que circula en Yogyakarta y Java Central, Indonesia: análisis de secuencia que cubre la región del sitio de escisión de furina (FCS) de la proteína espiga

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus responsible for the COVID-19 pandemic. The emergence of the new SARS-CoV-2 has been attributed to the possibility of evolutionary dynamics in the furin cleavage site (FCS) region. This study aimed to analyze the sequence of the FCS region in the spike protein of SARS-CoV-2 isolates that circulated in the Special Region of Yogyakarta and Central Java provinces in Indonesia. The RNA solution extracted from nasopharyngeal swab samples of confirmed COVID-19 patients were used and subjected to cDNA synthesis, PCR amplification, sequencing, and analysis of the FCS region. The sequence data from GISAID were also retrieved for further genome analysis. This study included 52 FCS region sequences. Several mutations were identified in the FCS region, i.e., D614G, Q675H, Q677H, S680P, and silent mutation in 235.57 C > T. The most important mutation in the FCS region is D614G. This finding indicated the G614 variant was circulating from May 2020 in those two provinces. Eventually, the G614 variant totally replaced the D614 variant from September 2020. All Indonesian SARS-CoV-2 isolates during this study and those deposited in GISAID showed the formation of five clade clusters from the FCS region, in which the D614 variant is in one specific cluster, and the G614 variant is dispersed into four clusters. The data indicated there is evolutionary advantage of the D614G mutation in the FCS region of the spike protein of SARS-CoV-2 circulating in the Special Region of Yogyakarta and Central Java provinces in Indonesia.(AU)