Mini Library Research Articles

Preferential HDAC6 inhibitors derived from HPOB exhibit synergistic antileukemia activity in combination with decitabine

Histone deacetylase 6 (HDAC6) is an emerging drug target to treat oncological and non-oncological conditions. Since highly selective HDAC6 inhibitors display limited anticancer activity when used as single agent, they usually require combination therapies with other chemotherapeutics. In this work, we synthesized a mini library of analogues of the preferential HDAC6 inhibitor HPOB in only two steps via an Ugi four-component reaction as the key step. Biochemical HDAC inhibition and cell viability assays led to the identification of 1g (highest antileukemic activity) and 2b (highest HDAC6 inhibition) as hit compounds. In subsequent combination screens, both 1g and especially 2b showed synergy with DNA methyltransferase inhibitor decitabine in acute myeloid leukemia (AML). Our findings highlight the potential of combining HDAC6 inhibitors with DNA methyltransferase inhibitors as a strategy to improve AML treatment outcomes.

Sequence- and Structure-Dependent Cytotoxicity of Phosphorothioate and 2'-O-Methyl Modified Single-Stranded Oligonucleotides.

Single-stranded oligonucleotides (SSOs) are a rapidly expanding class of therapeutics that comprises antisense oligonucleotides, microRNAs, and aptamers, with ten clinically approved molecules. Chemical modifications such as the phosphorothioate backbone and the 2'-O-methyl ribose can improve the stability and pharmacokinetic properties of therapeutic SSOs, but they can also lead to toxicity in vitro and invivo through nonspecific interactions with cellular proteins, gene expression changes, disturbed RNA processing, and changes in nuclear structures and protein distribution. In this study, we screened a mini library of 277 phosphorothioate and 2'-O-methyl-modified SSOs, with or without mRNA complementarity, for cytotoxic properties in two cancer cell lines. Using circular dichroism, nucleic magnetic resonance, and molecular dynamics simulations, we show that phosphorothioate- and 2'-O-methyl-modified SSOs that form stable hairpin structures through Watson-Crick base pairing are more likely to be cytotoxic than those that exist in an extended conformation. In addition, moderate and highly cytotoxic SSOs in our dataset have a higher mean purine composition than pyrimidine. Overall, our study demonstrates a structure-cytotoxicity relationship and indicates that the formation of stable hairpins should be a consideration when designing SSOs toward optimal therapeutic profiles.

Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity.

The MTS cell viability test was used to screen a mini library of natural and synthetic 1,4-naphthoquinone derivatives (1,4-NQs) from marine sources. This screening identified two highly effective compounds, U-443 and U-573, which showed potential in protecting Neuro-2a neuroblastoma cells from the toxic effects of rotenone in an in vitro model of neurotoxicity. The selected 1,4-NQs demonstrated the capability to reduce oxidative stress by decreasing the levels of reactive oxygen species (ROS) and nitric oxide (NO) in Neuro-2a neuroblastoma cells and RAW 264.7 macrophage cells and displayed significant antioxidant properties in mouse brain homogenate. Normal mitochondrial function was restored and the mitochondrial membrane potential was also regained by 1,4-NQs after exposure to neurotoxins. Furthermore, at low concentrations, these compounds were found to significantly reduce levels of proinflammatory cytokines TNF and IL-1β and notably inhibit the activity of cyclooxygenase-2 (COX-2) in RAW 264.7 macrophages. The results of docking studies showed that the 1,4-NQs were bound to the active site of COX-2, analogically to a known inhibitor of this enzyme, SC-558. Both substances significantly improved the behavioral changes in female CD1 mice with rotenone-induced early stage of Parkinson's disease (PD) in vivo. It is proposed that the 1,4-NQs, U-443 and U-573, can protect neurons and microglia through their potent anti-ROS and anti-inflammatory activities.

Revitalization of Taman Pendidikan Al Qur’an (TPA) in Padukuhan Nepi Kranggan Galur Kulonprogo

Abstract. As a nation with a majority Muslim population, early religious and moral education has a major contribution to the development of excellent Indonesian character in the future. Taman Pendidikan Al Qur'an (Qur’anic Education Center for Children -TPA) is a place to prepare the younger generation with good religious and moral provisions. Padukuhan Nepi, Kranggan Village, Galur Subdistrict also has a TPA which is managed by the mosque caretakers. However, due to the pandemic disaster which required people to reduce their social interactions in early 2020, TPA activities were temporarily suspended. For this reason, a TPA revitalization strategy is needed to attract students to return to study. The efforts to solve this problem were carried out in 2 (two) ways, firstly, organizing recitations for students by inviting little preachers, as an attraction for students to come back to TPA; Second, providing alternative learning tools, i.e. a mini library, to attract the attention of students to always come to TPA activities. The results of implementing this strategy show an increase in the attendance of students to participate in TPA activities.

Pembuatan Perpustakaan Mini Guna MeningkatkanMinat Baca Anak Di Desa Buana Bhakti

One of the problems that exists in the community of Buana Bhakti Village, Kerinci Kanan District, Siak Regency nowadays is the lack of interest in reading. One of the programs implemented in Buana Bhakti Village is the creation of a mini library. The aim of creating a mini library is to help the community, especially children, develop a love for the culture of interest in reading, increase learning experiences other than in the classroom and also as a center for community empowerment to develop literacy-based potential. The result of this program is that children are enthusiastic about visiting the library to study and read.

Analisis Pembiasaan Perilaku Berliterasi dalam Upaya Peningkatan Karakter oleh Siswa Kelas VI SD

Beginning reading and writing are stages of the learning process for elementary school students. Various studies have shown that the habit of reading quality literature contributes to a person's level of intelligence. Reading helps someone to see problems from various perspectives and consider them as challenges that must be solved. It's the same with literacy. Has the meaning and implications of basic reading and writing skills to the acquisition and manipulation of knowledge through written texts, from the metalinguistic analysis of grammatical units to the structure of spoken and written texts. From the several survey institutions, Indonesia ranks bottom and this shows that literacy skills in Indonesia are still low. This research aims to determine the literacy skills of students at SMP St. Ignatius and know the right strategy to improve students' literacy skills. Exclusive data collection was carried out in class VI with a total of 22 students. This research starts from October to December 2022. The results of this mini research are that the class mini library is efficient for students' reading habits. Then, it can be seen that students basically have a desire to read even though there are those who read only at a glance and see the title first. This can be overcome if the teacher regularly pays attention to students' reading activities until finally they get used to reading activities. Thus it can be concluded that SD Negeri 165730 students are still at the stage of reading habit.
 
 Keywords: books, literacy, students, mini library, school

Strategies and Efforts to Increase Children's Interest in Reading in Gampong Mamplam

The purpose of this study is to find alternatives to increase interest in reading among children, as an effort to overcome low interest in reading. Good reading interest is an indicator of literacy progress as well as an indicator of the nation's progress. The steps taken in this service are by having a mini library filled with interesting story books where every 5 days a week before starting the activity there is a reading together. This strategy is created and implemented by students with the aim of increasing reading interest in children in Mamplam village, with frequent reading every day makes children accustomed to reading activities. These strategies and efforts show the result that having a mini library is able to develop an interest in reading in children in Gampong Mamplam, which becomes a change in the children and makes them more enthusiastic about reading.

Urgensi Administrasi Kependudukan Desa Lau Tawar Kabupaten Dairi Perspektf UU No. 23 Tahun 2006

The problem in this research is how is the role of the Lau Tawar Village government in increasing awareness of the orderly population administration and civil registration in Lau Tawar Village, Tanah Pinem District, Dairi Regency. Because if you look at it, there are still many people in Lau Tawar Village who don't care about their population administration. Based on the Law of the Republic of Indonesia Number 23 of 2006 concerning the State Population Administration, it is obligated to provide protection and acknowledgment of the determination of personal status and legal status of every demographic and important event experienced by residents who are inside or outside the territory of the Republic of Indonesia.The purpose of this study is to analyze and describe how the role of the Lau Tawar Village government in increasing awareness of the orderly population administration and civil registration in Lau Tawar Village. and civil registration in Lau Tawar Village. The research method used by the researcher in this research is a sociological juridical approach. The data collection instruments used in this study consisted of interviews, observations, and documentation. The results of this study are the Lau Tawar Village government issued an appeal to the community, came directly to the house, provided a wifi network, printer and laptop. Factors supporting the orderly population administration are the availability of wifi at the village office and a mini library where data is stored. Inhibiting factors are human resources that are still lacking, lack of discipline in the village apparatus, low public awareness, and inadequate facilities.

Analysis Of Stress And Deformation In Parametric Furniture Using The Finite Element Method

One method of designing furniture is to use parametric design. Parametric design method is a design method in which design uses certain patterns. With the parametric design method, furniture that is very good in shape and aesthetics is produced, one of which is parametric TV table furniture. TV table is a type of furniture that has the function of placing a TV, multimedia supporting tv, mini library, and storage of other mini equipment. To carry out its function, furniture must also be tested for strength, one of which uses the finite element method with the help of ANSYS software version 18.1. The analysis aims to determine the stress and deformation. The simulation results with loads of 400N, 600N, 800N and 1.000N are maximum equivalent stress of 7,05x10-5 Pa, 1,05x106 Pa, 1,41x10-6 Pa, and 1,76x10-6 Pa. The highest maximum principal stress is equal to 1,16x10-5, 1,75x10-5, 2,33x10-5, and 2,92x10-5. Total deformation of 8,27x10-6m, 1,24x10-5m, 1,65x105m, and 2,06x10-5m. The conclusion of this study shows that the results of stress and deformation analysis have no change in shape and failure in load bearing. This shows that parametric TV table furniture can perform its function by being able to withstand TV loads and other furniture until 100Kg (1.000N) with safety factor 1,8.

Development of a Lysine-Based Poly(ester amide) Library with High Biosafety and a Finely Tunable Structure for Spatiotemporal-Controlled Protein Delivery

With the fast growth of protein therapeutics, efficient, precise, and universal delivery platforms are highly required. However, very few reports have discussed the progress of precisely spatiotemporal-controlled protein delivery. Therefore, a mini library of well-designed amino acid-based poly(ester amide)s derived from lysine (Lys-aaPEAs) has been developed. Lys-aaPEAs can interact with and encapsulate proteins into nanocomplexes via electrostatic interactions. The chemical structure of Lys-aaPEAs can be finely tuned by changing the type and molar ratio of the monomers. Studies of structure-function relationships reveal that the carbon chain length of diacid/diol segments, hydrophilicity, and electrical properties affect the polymer-protein interaction, cell-material interaction, and, therefore, the outcome of protein delivery. By modulating the structures of Lys-aaPEAs, the delivery systems could present customized physiochemical and biological properties and perform time- and space-specific protein release and delivery without causing any systematic toxicity. The screened systems exhibited prolonged hypoglycemic activity and superior biosafety in vivo, using insulin as a model protein and a mouse model bearing type 1 diabetes mellitus (T1DM). This work establishes a novel lysine-based polymer platform for spatiotemporal-controlled protein delivery and offers a paradigm of precise structure-function controllability for designing the next generation of polymers.

Nurturing Reading Culture: Establishing a Mini Library to Promote Literacy and Foster Children's Reading Interest in Cidikit Village, Bayah, Lebak, Banten

Nurturing Reading Culture: Establishing a Mini Library to Promote Literacy and Foster Children's Reading Interest in Cidikit Village, Bayah, Lebak, Banten

Screening of Big Pharma's Library against Various in-house Biological Targets.

Open innovation initiatives provide opportunities for collaboration and sharing of knowledge and experience between industry, academia, and government institutions. Through open innovation, Merck is offering a Mini Library of 80 carefully selected compounds from previous research and development projects to a broader scientific community for testing in academic drug discovery projects. These compounds are predominantly drug-like and cover a broad range of molecular targets. They could potentially interact with other enzymes, receptors, transporters, and ion channels of interest. The Mini Library was tested on seven in-house enzymes (bacterial MurA, MurC ligase, and DdlB enzyme, human MAO-A/B, human BChE, and murine AChE), and several hits were identified. A follow-up series of structural analogues provided by Merck gave a more detailed insight into the accessibility and the quality of the hit compounds. For example, sartan derivatives were moderate inhibitors of MurC, whereas bisarylureas were potent, selective, nanomolar inhibitors of hMAO-B. Importantly, 3-n-butyl-substituted indoles were identified as low nanomolar selective inhibitors of hBChE. All in all, the hit derivatives provide new starting points for the further exploration of the chemical space of high-quality enzyme inhibitors.

EKSISTENSI TOKOH UTAMA SEBAGAI PEREMPUAN JAWA DALAM NOVEL NAWUNG KARYA GALUH LARASATI: TINJAUAN FEMINISME EKSISTENSIALIS

The purpose of this study is to describe the existence of the main character as a Javanese woman in the novel Nawung by Galuh Larasati. To find out the existence of the main character, this research uses the feminist existentialist proposed by Simone De Beauvoir. The method in this research is descriptive qualitative analysis. The results of this study indicate that; 1) the main character is a Javanese woman who is labeled as intellectual; 2) the main character is a Javanese woman who works, and pursues many professions; 3) the main character is a Javanese woman who achieves social transformation, becomes an agent of change in her area by establishing a mini library since childhood, establishing a school for underprivileged children, and turning her village garden into a large natural park; and 4) the main character as a Javanese woman who refuses to be someone else, but independent and free to determine her own future.

Synthesis, Antiplasmodial, and Antileukemia Activity of Dihydroartemisinin-HDAC Inhibitor Hybrids as Multitarget Drugs.

Artemisinin-based combination therapies (ACTs) are the gold standard for the treatment of malaria, but the efficacy is threatened by the development of parasite resistance. Histone deacetylase inhibitors (HDACis) are an emerging new class of potential antiplasmodial drugs. In this work, we present the design, synthesis, and biological evaluation of a mini library of dihydroartemisinin–HDACi hybrid molecules. The screening of the hybrid molecules for their activity against selected human HDAC isoforms, asexual blood stage P. falciparum parasites, and a panel of leukemia cell lines delivered important structure–activity relationships. All synthesized compounds demonstrated potent activity against the 3D7 and Dd2 line of P. falciparum with IC50 values in the single-digit nanomolar range. Furthermore, the hybrid (α)-7c displayed improved activity against artemisinin-resistant parasites compared to dihydroartemisinin. The screening of the compounds against five cell lines from different leukemia entities revealed that all hydroxamate-based hybrids (7a–e) and the ortho-aminoanilide 8 exceeded the antiproliferative activity of dihydroartemisinin in four out of five cell lines. Taken together, this series of hybrid molecules represents an excellent starting point toward the development of antimalarial and antileukemia drug leads.

Overcoming the Impact of COVID-19 in the Densely Populated Area through “Taman Momong”

The COVID-19 Pandemic in Indonesia attacked public health and disrupted child care, especially for those in dense settlements and classified as low-income households. This research aims to help densely populated communities provide care facilities to optimize children's playgrounds and learning spaces for free to optimize children's physical and psychological growth and development during the Pandemic. By using the Participatory Action Research (PAR) method, this study resulted in three “Taman Momong” facilities equipped with children's play facilities, a mini library for children, the implementation of various educational activities needed by the community in the form of parenting workshops, the importance of parenting based on the fulfillment of children's rights, training on the use of Moringa and aloe vera plants to improve family nutrition, fulfill children's nutrition and herbal medicines to maintain family health. Thus, “Taman Momong” as green space can be beneficial in improving the physical and mental health of the community. Community activities at “Taman Momong” such as community parenting, gardening, recreation, and learning together show that psychologically and sociologically Taman Momong is the answer in overcoming parenting problems during the COVID-19 pandemic. This study shows that other communities can also use the existing vacant land to build “Taman Momong”. The society collaborates with the government to facilitate the park as a public space to support optimal care for their children

Identification of interacting proteins of Arabidopsis cyclophilin38 (AtCYP38) via multiple screening approaches reveals its possible broad functions in chloroplasts

AtCYP38, a thylakoid lumen localized immunophilin, is found to be essential for photosystem II assembly and maintenance, but how AtCYP38 functions in chloroplast remains unknown. Based on previous functional studies and its crystal structure, we hypothesize that AtCYP38 should function via binding its targets or cofactors in the thylakoid lumen. To identify potential interacting proteins of AtCYP38, we first adopted ATTED-II and STRING web-tools, and found 12 proteins functionally related to AtCYP38. We then screened a yeast two-hybrid library including an Arabidopsis genome wide cDNA with different domain of AtCYP38, and five thylakoid lumen-localized targets were identified. In order to specifically search interacting proteins of AtCYP38 in the thylakoid lumen, we generated a yeast two-hybrid mini library including the thylakoid lumenal proteins and lumenal fractions of thylakoid membrane proteins, and we obtained six thylakoid membrane proteins and nine thylakoid lumenal proteins as interacting proteins of AtCYP38. The interactions between AtCYP38 and several potential targets were further confirmed via pull-down and co-immunoprecipitation assays. Together, a couple of new potential candidate interacting proteins of AtCYP38 were identified, and the results will lay a foundation for unveiling the regulatory mechanisms in photosynthesis by AtCYP38.

Molecular docking studies of 1,3,4 -thiadiazoles as myeloperoxidase inhibitors

Myeloperoxidase (MPO) is a heterodimeric, cationic and glycosylated haeme enzyme which gets released under increased oxidative stress producing neutrophil oxidant, hypochlorous acid having the capacity to modify various biomolecules by chlorination and/or oxidation of sulfhydryl groups in proteins causing their inactivation and promoting inflammatory tissue damage. Different levels of hypochlorus acid are used as a trait marker for prescribing the disorders e.g. atherosclerosis, rheumatoid arthritis, lung cancer, Immuno-reactivity. Mini library of 22500 2,5disubstituted 1,3,4 thiadiazoles were docked with Myeloperoxidase in order to identify the potent inhibitor against the enzyme. The chemical nature of the protein and ligands greatly influence the performance of docking process. Keeping this fact in view, critical evaluation of the performance was performed by GLIDE by HTVS, SP and XP. The ADME parameters by QIKPROP and protein-ligand binding free energies were calculated using the Prime/MM-GBSA module of Schrödinger.Both hydrogen bonding and hydrophobic interactions contributed significantly for its ligand binding and core influence the target site through prominent hydrophobic and charged interaction with the backbone and side chain residues in the target site that improves the affinity of the molecule. The compound selected as potent inhibitor is having minimum binding affinity, maximum GScore and minimum FlexX energy. The amino acids residues ASP98, ASP94, THR100 and GLU 102 in the MPO gene domain active site form hydrogen bonds with the ligand. Compounds 3350-5150 showed better interaction with haeme enzyme for further understanding of structures, reliability and Biomolecularactivityy in connection with oxidative stress induced disorders.

Pendidikan Kewirausahaan Melalui Pengembangan Ekonomi Kreatif Sablon Cukil

The background of the service is that the development of the Kawruh Lumbung Studio is needed so that it can be further developed through the Cukil Screen Printing Business. The Cukil screen printing business is considered to be important expertise to accommodate creativity and improve the community's economy, especially young people to not migrate but focus on working to support the progress of Petir Village. The lumbung kawruh studio has several routine activities, including learning to read and write Javanese script, learning to dance and a mini library. The various creative potentials above, on the other hand, can be used as a medium for entrepreneurship education for youth in the area. The purpose of this service is to develop the art of Cukil (Cukil screen printing) which is applied to tshirts and bags, and to make it a medium for entrepreneurship education for youth in the area. The results of this service process include young people who have had cut-out screen printing skills through the entrepreneurship education process using the focus group discussion method, workshops andthe practice of screen printing.

Solid-phase synthesis of curcumin mimics and their anticancer activity against human pancreatic, prostate, and colorectal cancer cell lines

Curcumin is a bioactive natural compound with a wide range of pharmacological properties, including antitumor activity; however, its clinical application has been limited because of its low solubility, stability, and bioavailability. In this study, a solid phase approach was proposed for the combinatorial synthesis of a mini library of the mimics of curcumin in good purity and yield. The non-effective findings in pancreatic cancer cells switched to strong growth inhibition and cell death efficacy for PC3 prostate cancer cells, and mimic 9, in which tyrosol (TYR) and homovanillyl alcohol (HVA) units were linked by a phosphodiester bond, was quite effective not only in cell growth inhibition but also in causing strong cell death under the study conditions and treatments that were not effective in PANC1 cells. The results got more exciting when we also consider the findings in SW480 human colorectal carcinoma cell line, where the growth inhibitor effects were more in line with that of the PC3 cells, but the lack of cell death effect was more in line with the PANC1 cells.

STRATEGI MENINGKATKAN MUTU PENDIDIKAN MELALUI PROGRAM KELAS EXCELLENT SMP PLUS DARUSSALAM BANYUWANGI

Improving the quality of education is one of the main pillars in building education in Indonesia, because if education is of good quality, it will produce intelligent and competitive human resources. In order to improve the quality of education it is necessary to organize one of them by providing educational program services that accommodate the needs of special students to optimize their potential. One of the forums for special students, one of which is the holding of an excellent class program. This study aims to determine the strategy in improving the quality of education through the excellent class program at SMP Plus Darussalam Blokagung Tegalsari Banyuwangi. The subject of this research is the principal, WKS. The curriculum and the head of the excellent class dormitory are Al-Aziziyyah. This research method uses descriptive qualitative, data collection methods through observation, interviews, documentation, archival records and physical devices. The validity of the data uses credibility, transferability, dependability, and confirmability. The data analysis used is SWOT analysis. From the results of this study, the strategies used in improving the quality of education through the excellent class program at SMP Plus Darussalam Blokagung Tegalsari Banyuwangi include: (1) There is a selective selection process, (2) Improving the quality of teachers, (3) The existence of a study club, (4) The existence of a special dormitory for superior students, (5) The existence of a mini library, and (6) Strengthening the plus value in the community both in terms of academic and non-academic.