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Molecular pathogenesis of preeclampsia: microRNA hypothesis Mohd. Andalas; H. Harapan; Diky Mudhakir; Muhammad Ichsan; Natalia C. Pedroza; Saurabh Laddha
Proceedings of The Annual International Conference, Syiah Kuala University - Life Sciences & Engineering Chapter Vol 1, No 1 (2011): Life Sciences
Publisher : Syiah Kuala University

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (143.314 KB)

Abstract

The discovery of micro RNA (miRNA) in 1993 by Ambros and colleagues has a huge influence in pathogenesis theory, diagnosis and treatment approach of some diseases. Some studies have conducted to seek the association alterations of miRNA expression to incidences and severity of preeclampsia (PE). We have reviewed some studies that conducted to seek the association of miRNA and PE and we discussed the role of various miRNAs in PE pathogenesis. In summary, we have shown that many researchers have given evident that the different placental and plasma miRNA expression is associated with PE. Some studies also identified the novel candidate of miRNAs (and their pathways) that may be of etiologic relevance in the pathogenesis of PE. Base on review, specific miRNA have a role to down regulate of anti apoptosis genes, regulate angiogenics growth factors such as angiogenin, vascular endothelial growth factor (VEGF) B (VEGF-β), cysteine-rich 61 (CYR61), Placental growth factor (PlGF) and VEGF-A that have a role in angiogenesis. miRNA also have a role in  survival, migration, and capillary tube formation of HUVEC by targeted of c-kit. Some miRNAs target genes that participate in immunologic dysfunction, cell adhesion, cell cycle, and signaling. miRNA also have a roles in endothelial cell response to hypoxia, cell differentiation, and survival. A miRNA influence calcium signaling through negative regulations of the calmodulin-coding mRNAs, Mef2a and Gata4, mainly in smooth muscle cells that contribute to PE pathogenesis. These investigations provide novel targets for further investigation of the pathogenesis of PE and these differential miRNAs may be potential markers for the diagnosis and provide a potential therapeutic target for PE. Further investigations on posttranscriptional regulation in PE to evaluate biologic effects of identified miRNAs (including confirmations of miRNA and target gene interactions) are needed
TARGETING DESIGN TO THE LUNGAND PULMONARY INTRACELLULAR STRUCTURE OF ENDOGENOUS GENE BY IRQ MODIFIED NANO CARRIER Diky Mudhakir; Hidetaka Akita; Hideyoshi Harashima
Jurnal Sains Materi Indonesia Vol 12, No 2: FEBRUARI 2011
Publisher : Center for Science & Technology of Advanced Materials - National Nuclear Energy Agency

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (189.503 KB) | DOI: 10.17146/jsmi.2011.12.2.4606

Abstract

TARGETING DESIGN TO THE LUNGAND PULMONARY INTRACELLULAR STRUCTURE OF ENDOGENOUS GENE BY IRQ MODIFIED NANO CARRIER. Inhibition of angiogenesis is a novel strategy for the treatment of lung cancer. For efficient therapy, vectors must firstly reach the target tissue and subsequently demonstrate an efficient intracellular targeting. In this study, we attempted to design a vector for in vivo pulmonary targeting which was able to deliver small interfering RibonucleicAcid (siRNA) for endogenous gene of angiogenesis in pulmonary endothelial cells. siRNA was condensed with polycation agent and encapsulated in lipidous nano carrier. To obtain high level of lung accumulation, we controlled the surface of nano-carrier by changing the length of Polyethylene glycol (PEG) moiety. These nano carriers showed prominent Ribonucleic acid interference (RNAi) effect, when luciferase gene was used as a target. In addition, an efficient transgene knockdown of Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), a responsible gene of angiogenesis, can be obtained by the Instantaneous Respiratory Exchange Ratio (IRQ) modified nano carrier with the use of Stearyl-R8 (STR-R8) peptide, known as an endosomal membrane inducer. In conclusion, pulmonary targeting of nano carrier by encapsulating siRNA can be developed by controlling the PEG length and the structure of nano carrier for efficient intracellular targeting.
Hydrogenated Palm Fatty Acid Distillate as Raw Materials for Magnesium Stearate Alternatives Dianika Lestari; Abdu Ravi Zakaria; Dwi Rokhmat Setiawan; Shelly Shelly; Melia Laniwati; Ardiyan Harimawan; Muhamad Insanu; Diky Mudhakir
Journal of Engineering and Technological Sciences Vol. 53 No. 3 (2021)
Publisher : Institute for Research and Community Services, Institut Teknologi Bandung

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.5614/j.eng.technol.sci.2021.53.3.3

Abstract

Palm fatty acid distillate (PFAD) was used as raw material to produce solid lubricant, or anti-adherent, for confectionery or pharmaceutical products. To improve the degree of saturation, the PFAD was hydrogenated by using two methods: gaseous hydrogenation (GH) and catalytic transfer hydrogenation (CTH) using ammonium formate to produce hydrogenated PFAD (HPFAD). The HPFAD was saponified with MgO to produce magnesium salts of hydrogenated PFAD (Mg-HPFAD). The objective of this research was to investigate the effect of hydrogen concentration and reaction temperature on the iodine value of HPFAD and to investigate the characteristics of paracetamol tablets when using Mg-HPFAD as lubricant compared to commercial Mg-stearate. The HPFAD produced by CTH had a lower iodine value than the HPFAD produced by GH. The lowest iodine value was obtained after CTH using 3.6 M ammonium formate at 90°C. Paracetamol tablets with Mg-PFAD or Mg-HPFAD lubricant showed higher dissolution of active compounds with similar friability, frictiability, and hardness compared to paracetamol tablets with Mg-stearate.
Vitamin E Extraction from Magnesium Salts of Palm Fatty Acid Distillates Dianika Lestari; Khalisa Putri Aqilah; Salsafia Putri; Ardiyan Harimawan; Diky Mudhakir; Muhamad Insanu
Journal of Engineering and Technological Sciences Vol. 54 No. 1 (2022)
Publisher : Institute for Research and Community Services, Institut Teknologi Bandung

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.5614/j.eng.technol.sci.2022.54.1.2

Abstract

This research studied how the type of organic solvent and the number of extraction stages affect the vitamin E cumulative extraction yield and recovery rate from Mg-PFAD. First, PFAD was saponified to produce Mg-PFAD, then vitamin E was extracted from the Mg-PFAD using ethanol, isopropanol, or hexane, followed by evaporation to produce vitamin E concentrate. Three-stage hexane extraction with a solvent to Mg-PFAD mass ratio of 3 kg solvent/kg Mg-PFAD produced the highest vitamin E recovery rate. Organic solvent with a lower polarity gave a higher extraction yield and recovery rate of vitamin E from Mg-PFAD. In general, an increase of the number of extraction stages led to an increase of the vitamin E extraction yield and recovery rate from Mg-PFAD.
Antioxidant Activity of Vitamin E Concentrate from Magnesium Salts of Palm Fatty Acid Distillate (Mg-PFAD) Dianika Lestari; Khalisa Putri Aqilah; Salsafia Putri; Ardiyan Harimawan; Diky Mudhakir; Muhamad Insanu
Reaktor Volume 21 No. 1 March 2021
Publisher : Dept. of Chemical Engineering, Diponegoro University

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (829.293 KB) | DOI: 10.14710/reaktor.21.1.35-43

Abstract

Vitamin E concentrate was produced through saponification of palm fatty acid distillates (PFAD) and magnesium oxide to form Mg-PFAD, followed by three-stages vitamin E extraction with isopropanol, hexane, or ethanol. The vitamin E-rich extracts were evaporated to remove solvent and produced vitamin E concentrate. The objectives of this research were to investigate the effect of organic solvent’s types and solvent to Mg-PFAD mass ratios on vitamin E concentration, solvent selectivity, and antioxidant activity of the vitamin E concentrate. Vitamin E concentrates obtained after isopropanol extraction had vitamin E concentration of 784 ppm with vitamin E recovery of 16 mg tocopherol/100 mg tocopherol in Mg-PFAD, while vitamin E concentrates obtained after hexane extraction had vitamin E concentration of 574 ppm with vitamin E recovery of 35 mg tocopherol/100 mg tocopherol in Mg-PFAD. Isopropanol extraction produced vitamin E concentrate with the highest selectivity for vitamin E and the highest antioxidant activity of 79% IC. It was found that vitamin E concentration was not proportional to the antioxidant activity of the vitamin E concentrate.Keywords: Direct solvent extraction, palm fatty acid distillate, saponification, vitamin E, unsaponifiable matter 
EVALUASI SEDIAAN FISIK EMULGEL MENGANDUNG MINYAK ATSIRI RIMPANG TEMU PUTIH (Curcuma zedoaria, (Berg.) Roscoe) Nur Mahdi; Diky Mudhakir; Dolih Gozali
Media Farmasi: Jurnal Ilmu Farmasi Vol 15, No 2: September 2018
Publisher : Universitas Ahmad Dahlan

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (674.893 KB) | DOI: 10.12928/mf.v15i2.12657

Abstract

Temu putih atau disebut juga kunir putih merupakan salah satu spesies dari familiZingiberaceae yang telah dikomersilkan penggunaan rimpangnya sebagai tanaman obat.Komponen terbesar dari rimpang temu putih, yaitu minyak atsiri yang mempunyai efekantiinflamasi. Penggunaan rimpang temu putih sebagai antiinflamasi di masyarakatmasih secara empiris, dengan mengoleskan air perahan rimpang temu putih pada kulit.Untuk meningkatkan efektivitas penggunaan minyak atsiri yang terkandung dalam temuputih, dilakukan formulasi emulgel yang mengandung minyak atsiri denganpenambahan PEG 8 beeswax agar didapat sediaan emulgel yang stabil, baik dan amandigunakan. Tahap penelitian yang dilakukan meliputi penyiapan bahan, determinasibahan, skrining fitokimia, destilasi menggunakan uap-air, analisis komponen kimiadengan GC-MS, serta uji kualitatif minyak atsiri dengan sediaan emulgel yangmengandung minyak atsiri, formulasi emulgel mengandung minyak atsiri denganmenggunakan emulsifying wax konsentrasi 6,5%, 7%, 7,5%, dan 8%. Evaluasi sediaanmeliputi pengamatan organoleptik, pH, viskositas, sentrifugasi, serta uji hedoniksediaan. Berdasarkan hasil evaluasi pengamatan organoleptik, pH, viskositas,sentrifugasi, serta uji hedonik sediaan menunjukkan bahwa kestabilan dalam batasrentang yang dibolehkan. Formulasi emulgel yang terbaik ditunjukkan pada formula ke-4 pada konsentrasi PEG 8 beeswax 8%.
Uji Disolusi Terbanding Zat Karbamazepin dalam Bentuk Sediaan Tablet - Satrialdi; Sukmadjaja Asyarie; Diky Mudhakir
Acta Pharmaceutica Indonesia Vol. 36 No. 1 & 2 (2011)
Publisher : School of Pharmacy Institut Teknologi Bandung

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Abstract

Dalam penelitian ini telah dilakukan uji ekivalensi produk tablet karbamazepin secara in vitro dengan menggunakan uji disolusi terbanding. Uji dilakukan terhadap produk inovator, produk bermerek I, dan produk bermerek II menggunakan 3 medium uji yaitu medium pH 1,2; pH 4,5; dan pH 6,8 dengan pengambilan sampel pada menit ke-10, 15, 30, 45, dan 60. Penetapan kadar dilakukan menggunakan metode spektrofotometri UV pada panjang gelombang 285 nm. Hasil uji disolusi terbanding dianalisis menggunakan faktor kemiripan (f2). Dari hasil uji disolusi terbanding, kedua produk uji tidak ekivalen terhadap produk inovator.
Effects of gelatin and glutaraldehyde concentrations on characteristics of Cantigi (Vaccinium varingiaefolium Miq.) extract loaded gelatin nanoparticles as antioxidant Kosasih Kosasih; Wahono Sumaryono; Diky Mudhakir; Agus Supriyono; Yulius Evan Christian; Ruth Debora
Journal of halal product and research (JPHR) Vol. 4 No. 1 (2021): Journal of Halal Product and Research (JHPR)
Publisher : Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/jhpr.vol.4-issue.1.1-7

Abstract

Cantigi is an endemic plant of sub-alpine area of Mount Tangkuban Parahu in Bandung, Indonesia. Previous study showed ethanol extract of young red leaves had antioxidant activity, however no information on this activity if changed into nanoparticles. The purpose of this study was to determine the effects of gelatin and glutaraldehyde concentrations on the characteristics of Cantigi extract loaded gelatin nanoparticles and to evaluate the antioxidant activity of nanoparticles. Cantigi leaves were extracted by maceration using n-hexane, ethyl acetate, and ethanol 96%. The ethanol extract was dried, made into nanoparticles by varying gelatin (0.1; 0.2; and 0.3 g) and glutaraldehyde (0.1; 0.2; and 0.3 mL) amounts, and conducted at 500 rpm and 40 °C for 3 hours. Nanoparticles were evaluated for particle size, zeta potential, morphology, and antioxidant activity. Nanoparticles with glutaraldehyde amount variation had particle sizes (PS) of 105.9±26.2; 37.1±8.7; and 32.5±7.4 nm; polydispersity indeces (PI) of 0.508; 0.717; and 0.563; zeta potential values (ZPV) of 0.55; 0.89; and 0.78 mV; and antioxidant activities (IC50) of 56.15±0.16; 53.67±0.10; and 51.57±0.39 ppm, respectively. Then, nanoparticles with gelatin amounts variation had PS of 22.5±5.1; 37.1±8.7; and 83.3±21 nm; PI of 0.604; 0.717; 0.326; ZPV of 1.27; 0.89; 0.18 mV; and antioxidant activities of 51.58±0.19; 53.67±0.12; and 55.46±0.04 ppm, respectively. Nanoparticle morphology was spherical. Cantigi leaf extract can be made into gelatin nanoparticles; the smaller the concentration of the polymer used and higher the concentration of the glutaraldehyde, the smaller the resulted particle size and increased antioxidant activity. Antioxidant activities of nanoparticles was lower than those of the extract (IC50 16.84±0.30 ppm).
Enhanced delivery of anti-inflammatory therapeutics using pH-responsive histidine-modified poly-L-lysine on mesoporous silica nanoparticles Permana, Zuliar; Xeliem, Jovinka N.; Zefrina, Normalita F.; Hanum, Latifa F.; Nirmalayanti, Ni LPKV.; Permana, Benny; Mudhakir, Diky
Narra J Vol. 5 No. 1 (2025): April 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i1.1815

Abstract

Mesoporous silica nanoparticles (MSNs) are effective platforms for drug delivery due to their high surface area, adjustable pore sizes, and biocompatibility. The aim of this study was to explore the application of histidine-modified poly-L-lysine (PLL-His) as a pH-responsive gatekeeper to control the release of an anti-inflammatory agent, celecoxib, from MSNs. MSNs were synthesized through a sol-gel process using cetyltrimethylammonium bromide (CTAB) as a template and were functionalized with amine groups using (3-aminopropyl)triethoxysilane (APTES). Drug loading was achieved via adsorption in ethanol. Subsequently, poly-L-lysine (PLL) and PLL-His were conjugated to the MSNs using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC) and N-hydroxysuccinimide (NHS) to form MSN-NH2-Drug-PLL and MSN-NH2-Drug-PLL-His constructs. Characterization of these particles was conducted using Fourier-transform infrared (FT-IR) spectroscopy, Brunauer-Emmett-Teller (BET) analysis, and particle size analysis. Results showed that the particle size of MSN-NH2-drug-PLL and MSN-NH2-drug-PLL-His was 237.10±6.56 nm and 234.03±14.65 nm, respectively, indicating suitability for cellular uptake. BET analysis confirmed the increased surface area and pore volume after the removal of CTAB, demonstrating successful mesopore formation. Drug release tests were performed in simulated gastric (pH 1.2) and physiological (pH 7.4) conditions, showing that PLL-His-modified MSNs exhibited minimal release in acidic conditions and sustained release at physiological pH. The PLL-His effectively functioned as a pH-responsive gatekeeper, enhancing drug targeting and reducing premature release. This study highlights the potential of PLL-His-modified MSNs as a promising model for pH-sensitive, targeted drug delivery, with potential applications across various therapeutic areas requiring precise release profiles. This approach could significantly improve therapeutic outcomes and patient compliance, particularly in disease contexts where pH variability is a critical factor. Overall, the integration of PLL-His as a pH-responsive gatekeeper represents a significant advancement in the design of smart drug delivery systems.
Design of lipid nanoparticle (LNP) containing genetic material CRISPR/Cas9 for familial hypercholesterolemia Prasetia, I GNJA.; Kurniati, Neng F.; Riani, Catur; Mudhakir, Diky
Narra J Vol. 5 No. 1 (2025): April 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i1.2217

Abstract

Familial hypercholesterolemia is a genetic disorder caused by mutations in the low-density lipoprotein receptor gene (LDLR) and the current treatment still focuses on symptom management. The aim of this study was to develop a lipid nanoparticle (LNP)-based delivery system for the CRISPR/Cas9 component in correcting LDLR gene mutations. LNPs were prepared using an ultrasonic-solvent emulsification technique by varying the surfactant: oil ratio (SOR), homogenization speed and time, and sonication time. Next, the LNP surface was modified by adding DSPE-PEG2000-NH2 and polyethyleneimine. The next stage is to design the single guide RNA (sgRNA) and Donor DNA wildtype (Donor DNA wt). This genetic material was complexed with LNP and then transfected into Hepa1-6 LDLR mt cells, an in vitro representation of cells suffering from familial hypercholesterolemia. This optimization process produced LNPs with a particle size of 118.6±0.8 nm and a polydispersity index of 0.34±0.03. The LNP surface modification resulted in a zeta potential of +7.5 mV. A transmission electron microscope (TEM) analysis howed spherical morphology with size distribution following a regular pattern. LNP cell viability tests showed good biocompatibility at concentrations <15 mM with a half-maximal inhibitory concentration (IC50) value of 27.7 mM. The dominant cellular uptake mechanism of LNP was through the clathrin-mediated endocytosis (CME) pathway. The Hepa1-6 LDLR mt cell model was successfully produced with the transfecting agent Lipofectamine 3000 by homology-directed repair (HDR) mechanism. The LNP-genetic material complex with a ratio of sgRNA:Cas9:Donor DNA wt (1:1:0.04) showed an increase in LDLR gene expression of 3.3±0.2 times and LDLR protein levels reached 12.95±0.25 ng/mL on day 4 after transfection. The results of this study indicate that the developed LNP-based delivery system has the potential for gene therapy applications in familial hypercholesterolemia.