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11 result(s) for "Mahendra, Isa"
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Radiosynthesis, Stability, Lipophilicity, and Cellular Uptake Evaluations of 131IIodine-α-Mangostin for Breast Cancer Diagnosis and Therapy
The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [131I]Iodine-α-mangostin ([131I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [131I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including −20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [131I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [131I]I-AM has an RCP above 90% after three days of storage at −20 °C. A significant difference was obtained between [131I]I-AM uptake in T47D and Vero cells. Based on these results, [131I]I-AM has been prepared with high RCP, stable at −20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [131I]I-AM as a diagnostic and therapeutic agent for breast cancer.
Biogas Production from Coffee Pulp and Chicken Feathers Using Liquid- and Solid-State Anaerobic Digestions
Agricultural waste, particularly lignocellulose, has been used in the second generation of biogas. Coffee pulp and chicken feathers can be developed as biogas raw materials because of their suitability as a biogas substrate. This study investigates the effect of the percentage of total solids (TS), carbon to nitrogen ratio (C/N, g/g), and delignification pretreatment on biogas production from coffee pulp and chicken feathers, and aims to compose kinetics using the modified Gompertz model. The results show that adjusting the percentage of TS at low-level speeds up the degradation process, which increases chemical oxygen demand (COD) reduction and biogas production. COD reduction and biogas production increase optimally at the 25 (g/g) C/N ratio. Pretreatment delignification aids microorganisms in substrate decomposition, resulting in faster COD reduction and biogas conversion. The 25% TS and 25 (g/g) C/N ratio with the delignification process achieved the best biogas production, with biogas production of 10,438.04 mL. The Gompertz method shows that the difference in TS percentage can influence biogas production. Moreover, the method shows that biogas production is higher with the delignification process than without it.
Molecular Docking Study of Pramipexole Derivatives as Radiopharmaceutical Candidates for Brain Imaging
Neurodegenerative diseases are a global priority disease. According to the World Health Organization (WHO), it is estimated that by 2050, there will be 152 million people with neurodegenerative diseases. Currently, the method used for brain imaging is PET/CT, with the most widely used radiopharmaceutical being 18F-FDG [7,8]. 18F-FDG is used to determine brain glucose metabolism, however the 18F-FDG does not have a specific receptor. Pramipexole compounds can cross the blood-brain barrier and have high specificity for dopamine receptors. By modifying and labelling the structure of pramipexole derivatives, it is expected to obtain pramipexole derivatives with a good affinity to the dopamine receptor. In order to reduce the risk of failure, radiation hazard, and research funds, in this research, a molecular docking study was carried out using the targeted docking method between dopamine receptor proteins and 22 pramipexole derivatives using AutoDock 4, GaussView software for structure preparation, Gaussian software for energy calculation, and Biovia Discovery Studio for structure visualization. The experimental results showed that the free binding energy of pramipexole derivatives for the dopamine receptor was obtained in the range of -2.81 to -5.84 kcal/mol. The best free binding energy value was obtained for compound PD-7, with a free binding energy value of -5.84 kcal/mol, while the RMSD value obtained was 0.6 A°, and amino acid residues that interacted with compound PD-7 among others: Leu347, Leu343, Tyr198, Leu199, Glu202, Phe201, and Val203 with hydrophobic and hydrogen bond interactions. The PD-7 compound was labeled using the radioisotope iodine-131 based on the free binding energy value. From the experimental results, compound 131I-PD-7 showed a free binding energy value of -4.66 kcal/mol and interacts with the similar amino acid residues as compound PD-7. These results indicate that the compound 131 I-PD-7 is a potential candidate to be studied further as a radiopharmaceutical candidate for brain imaging.
Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2—A Candidate for Passive Immunization against COVID-19
The coronavirus disease 2019 (COVID-19) has become a substantial threat to the international health sector and the global economy. As of 26 December 2021, the number of mortalities resulting from COVID-19 exceeded 5.3 million worldwide. The absence of an effective non-vaccine treatment has prompted the quest for prophylactic agents that can be used to combat COVID-19. This study presents the feasibility of chicken egg yolk antibody (IgY) anti-receptor-binding domain (RBD) spike SARS-CoV-2 as a strong candidate to neutralize the virus for application in passive immunization. For the purpose of preclinical studies, we radiolabeled IgY anti-RBD spike SARS-CoV-2 with radionuclide iodine-131. This allowed us to evaluate several biological characteristics of IgY in vitro, in vivo, and ex vivo. The preclinical data suggest that IgY anti-RBD spike SARS-CoV-2 could specifically bind to the SARS-CoV-2 antigens; however, little uptake was observed in normal cells (MRC-5) (<2%). Furthermore, the ex vivo biodistribution study revealed that IgY predominantly accumulated in the trachea of normal mice compared to other organs. We also found that IgY possessed a good safety profile when used as an intranasal agent. Taken together, we propose that IgY anti-RBD spike SARS-CoV-2 has the potential for application in passive immunization against COVID-19.
Translocator Protein 18 kDa (TSPO): A Promising Molecular Target for Image-Guided Surgery of Solid Cancers
Translocator protein 18-kDa, broadly known as TSPO, is a mitochondrial membrane protein, previously identified as the peripheral benzodiazepine receptor (PBR). TSPO involves in a broad number of biochemical events, such as steroidogenesis, mitochondrial cholesterol transport, cell survival and death, cell proliferation, and carcinogenesis. Several investigations have reported the roles of TSPO in various types of cancers, including colorectal cancer, brain cancer, melanoma, breast cancer, prostate cancer, and lung cancer. It was found that TSPO is upregulated in cancer cells, and it appears that its expression is parallel with an aggressive phenotype and/or poor prognosis. As a consequence, there is great potential for developing diagnostic and prognostic tools targeting the TSPO. In this regard, several radioligands targeting the TSPO have been identified, and some of the candidates have advanced to clinical trials. In recent years, image-guided surgery using hybrid probes bearing radioactive and fluorescence molecules has demonstrated promising outcomes in animal and human studies, and thus might serve as a valuable surgical navigator during cancer surgery. In general, current hybrid probes are built from various molecular platforms, including small molecules, nanoparticles, and antibodies. Although several TSPO-targeted imaging probes have been developed, their development for image-guided surgery of cancers is scarce. This review highlights recent findings of the involvement of TSPO in carcinogenesis, and provides a new perspective on the potential application of TSPO-targeted hybrid probes for image-guided surgery.
Evaluation of Silver Nanoparticles Addition in Periodontal Dressing For Wound Tissue Healing By 99mTc-ciprofloxacin
Objective: Periodontal dressing is a protective material that is used on post-surgical periodontal to protect the surface of the wound and provides a comfort sense to patient. This study was conducted to determine the effect of periodontal dressings containing silver nanoparticles by evaluating inflammatory parameters using 99mTc-ciprofloxacin; a radiopharmaceutical that can be used for diagnosing infection and inflammation. Methods: This research was carried out using purely experimental 24 male Sprague Dawley rats and divided into 4 groups. First group is a group without any treatment, second group was the positive control group (excision procedure and given CoePak(R)), third group was negative group (only excision procedure) and fourth group (excision procedure and given CoePak (R) with silver nanoparticles). On second and fourth days after the procedure, each group was observed of inflammation inside of the excision by injecting 99mTc-ciprofloxacin through vein and after one hour the rat was sacrificed and dextra palate organ of each rat was counted by Single Channel Analyzer to determine the accumulation of 99mTc-ciprofloxacin. Results: In rats given CoePak (R) with silver nanoparticles showed a tendency or inclination data which is good in giving effect to promote healing compare to positive control group on day 4 with less accumulation of 99mTc-ciprofloxacin in dextra palate. Conclusion: Addition of silver nanoparticles in periodontal dressing gave a good effect for wound tissue healing.
Phosphorus-32 labelled irradiated bovine hydroxyapatite for radiosynovectomy
Radiosynovectomy is a treatment for patients with rheumatoid arthritis (RA) that affects joints by injecting beta-emitting radiopharmaceuticals into the synovial membrane of inflamed joints. In this study, we established 32 Phosphorus labelled hydroxyapatite ( 32 P-HAp) using gamma-irradiated hydroxyapatite material from bovine. Our results showed that gamma-irradiation of bovine HAp tends to agglomerate the particle and form a micro-sized HAp. In addition, irradiated HAp exhibited Ca/P ratio higher than non-irradiated HAp. The ex-vivo biodistribution studies exhibited a high accumulation of irradiated 32 P-HAp in the inflamed joints, resulting in good therapeutic effectiveness. Our study demonstrated the potential of 32 P-HAp from irradiated bovine hydroxyapatite for radiosynovectomy therapy.
Radiosynthesis, Stability, Lipophilicity, and Cellular Uptake Evaluations of 131IIodine-α-Mangostin for Breast Cancer Diagnosis and Therapy
The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [131I]Iodine-α-mangostin ([131I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [131I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including -20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [131I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [131I]I-AM has an RCP above 90% after three days of storage at -20 °C. A significant difference was obtained between [131I]I-AM uptake in T47D and Vero cells. Based on these results, [131I]I-AM has been prepared with high RCP, stable at -20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [131I]I-AM as a diagnostic and therapeutic agent for breast cancer.The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [131I]Iodine-α-mangostin ([131I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [131I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including -20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [131I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [131I]I-AM has an RCP above 90% after three days of storage at -20 °C. A significant difference was obtained between [131I]I-AM uptake in T47D and Vero cells. Based on these results, [131I]I-AM has been prepared with high RCP, stable at -20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [131I]I-AM as a diagnostic and therapeutic agent for breast cancer.
Radiosynthesis, Stability, Lipophilicity, and Cellular Uptake Evaluations of sup.131IIodine-α-Mangostin for Breast Cancer Diagnosis and Therapy
The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [[sup.131I]]Iodine-α-mangostin ([[sup.131]I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [[sup.131]I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including −20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [[sup.131]I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [[sup.131]I]I-AM has an RCP above 90% after three days of storage at −20 °C. A significant difference was obtained between [[sup.131]I]I-AM uptake in T47D and Vero cells. Based on these results, [[sup.131]I]I-AM has been prepared with high RCP, stable at −20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [[sup.131]I]I-AM as a diagnostic and therapeutic agent for breast cancer.
Synthesis and Biological Evaluation of New Fluorescent Probe BPN-01: A Model Molecule for Fluorescence Image-guided Surgery
Fluorescence image-guided surgery (FIGS) can serve as a tool to achieve successful resection of tumour tissues during surgery, serving as a surgical navigator for surgeons. FIGS relies on the use of fluorescent molecules that can specifically interact with cancer cells. In this work, we developed a new model of fluorescent probe based on benzothiazole-phenylamide moiety featuring the visible fluorophore nitrobenzoxadiazole (NBD), namely BPN-01 . This compound was designed and synthesised for potential applications in the tissue biopsy examination and ex-vivo imaging during FIGS of solid cancers. The probe BPN-01 exhibited favourable spectroscopic properties, particularly in nonpolar and alkaline solvents. Moreover, in vitro fluorescence imaging revealed that the probe appeared to recognise and be internalised in the prostate (DU-145) and melanoma (B16-F10) cancer cells, but not in the normal cells (myoblast C2C12). The cytotoxicity studies revealed that probe BPN-01 was not toxic to the B16 cells, suggesting excellent biocompatibility. Furthermore, the computational analysis showed that the calculated binding affinity of the probe to both translocator protein 18 kDa (TSPO) and human epidermal growth factor receptor 2 (HER2) was considerably high. Hence, probe BPN-01 displays promising properties and may be valuable for visualising cancer cells in vitro. Furthermore, ligand 5 can potentially be labelled with NIR fluorophore and radionuclide, and serves as a dual imaging agent for in vivo applications.