bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Withaferin-A, Withanone, and Caffeic Acid Phenethyl Ester on
DNA Methyltransferases: Potential in Epigenetic Cancer Therapy
Authors: Kumar Vipul , Dhanjal Jaspreet Kaur , Sari Anissa Nofita , Khurana Mallika , Kaul Sunil C. , Wadhwa Renu , Sundar Durai 
Published: July 2023

Background:
DNA methyltransferases (DNMTs) have been reported to be potential
drug targets in various cancers. The major hurdle in inhibiting DNMTs is the lack of knowledge
about different DNMTs and their role in the hypermethylation of gene promoters in cancer cells.
Lack of information on specificity, stability, and higher toxicity of previously reported DNMT inhibitors
is the major reason for inadequate epigenetic cancer therapy. DNMT1 and DNMT3A are
the two DNMTs that are majorly overexpressed in cancers.

Objective:
In this study, we have presented computational and experimental analyses of the potential
of some natural compounds, withaferin A (Wi-A), withanone (Wi-N), and caffeic acid
phenethyl ester (CAPE), as DNMT inhibitors, in comparison to sinefungin (SFG), a known dual inhibitor
of DNMT1 and DNMT3A.

Methods:
We used classical simulation methods, such as molecular docking and molecular dynamics
simulations, to investigate the binding potential and properties of the test compounds with
DNMT1 and DNMT3A. Cell culture-based assays were used to investigate the inactivation of
DNMTs and the resulting hypomethylation of the p16INK4A promoter, a key tumour suppressor that
is inactivated by hypermethylation in cancer cells, resulting in upregulation of its expression.

Results:
Among the three test compounds (Wi-A, Wi-N, and CAPE), Wi-A showed the highest
binding affinity to both DNMT1 and DNMT3A; CAPE showed the highest affinity to DNMT3A,
and Wi-N showed a moderate affinity interaction with both. The binding energies of Wi-A and
CAPE were further compared with SFG. Expression analysis of DNMTs showed no difference between
control and treated cells. Cell viability and p16INK4A expression analysis showed a dose-dependent
decrease in viability, an increase in p16INK4A, and a stronger effect of Wi-A compared to
Wi-N and CAPE.

Conclusion:
The study demonstrated the differential binding ability of Wi-A, Wi-N, and CAPE to
DNMT1 and DNMT3A, which was associated with their inactivation, leading to hypomethylation
and desilencing of the p16INK4A tumour suppressor in cancer cells. The test compounds, particularly
Wi-A, have the potential for cancer therapy.
Antimicrobial Activity of Halogen- and Chalcogen-Functionalized Thiazoloquinazolines
Authors: Kut Diana , Kut Mykola , Komarovska-Porokhnyavets Olena , Kurka Maria , Onysko Mykhaylo , Lubenets Vira 
Published: July 2023

:
The investigation is devoted to the assessment of the potential antimicrobial use of new chalcogen-
functionalized thiazolo[2,3-b]quinazolin-5-ones, halides and trihalides of thiazolo[3,2-
a]quinazolin-10-ium and tribromides thiazino[3,2-a]quinazolin-11-ium. The compounds under study were
obtained by electrophilic intramolecular heterocyclization. A high bactericidal and fungicidal effect
against some gram-positive and gram-negative bacteria and fungi has been revealed for the investigated
compounds. The "structure-activity" relationship has been established; the influence of the chalcogen's
nature and the type of substituents in the thiazoline and pyrimidine cycles on the biological activity of the
investigated thiazolo- and thiazinoquinazolines is shown. Angular 4-methyl-5-oxo-1-
((trihalogenotellanyl)methylidene)-8-(trifluoromethyl)-1,2,4,5-tetrahydrothiazolo[3,2-a]quinazolin-10-
ium halides have been found to show the highest bactericidal activity to the gram-negative culture of
Escherichia coli.
Multiple Sclerosis Risk Among Anti-tumor Necrosis Factor Alpha Users:
A Methodological Review of Observational Studies Based on Real-world
Data
Authors: Li Lingyi , Etminan Mahyar , Kaplan Gilaad G. , Tremlett Helen , Xie Hui , Aviña-Zubieta J. Antonio 
Published: July 2023

Abstract:
Epidemiologic studies on the risk of multiple sclerosis (MS) or demyelinating events associated
with anti-tumor necrosis factor alpha (TNFα) use among patients with rheumatic diseases
or inflammatory bowel diseases have shown conflicting results. Causal directed acyclic graphs
(cDAGs) are useful tools for understanding the differing results and identifying the structure of potential
contributing biases. Most of the available literature on cDAGs uses language that might be
unfamiliar to clinicians. This article demonstrates how cDAGs can be used to determine whether
there is a confounder, a mediator or collider-stratification bias and when to adjust for them appropriately.
We also use a case study to show how to control for potential biases by drawing a cDAG
depicting anti-TNFα use and its potential to contribute to MS onset. Finally, we describe potential
biases that might have led to contradictory results in previous studies that examined the effect of
anti-TNFα and MS, including confounding, confounding by contraindication, and bias due to
measurement error. Clinicians and researchers should be cognizant of confounding, confounding
by contraindication, and bias due to measurement error when reviewing future studies on the risk
of MS or demyelinating events associated with anti-TNFα use. cDAGs are a useful tool for selecting
variables and identifying the structure of different biases that can affect the validity of observational
studies.
Targeting Glutamine Metabolism through Glutaminase Inhibition Suppresses Cell
Proliferation and Progression in Nasopharyngeal Carcinoma
Authors: Su Chang , Li Minghan , Yang Yuxin , Wang Ziying , Wang Qianru , Wang Weijia , Ma Xuemin , Jie Rongrong , Chen Huaihong , Li Xiangping , Lu Juan 
Published: July 2023

Background:
Glutaminase (GLS), the key enzyme involved in glutamine metabolism, has been identified as
a critical player in tumor growth and progression. The GLS inhibitor CB-839 has entered several clinical trials against
a variety of tumors.

Objective:
Our study aimed to investigate the role and underlying mechanism of GLS and its inhibitor CB-839 in nasopharyngeal
carcinoma (NPC).

Methods:
The expression, downstream genes, and signaling pathways of GLS in NPC were determined by real-time
polymerase chain reaction (RT-PCR), PCR array, western blotting (WB), and immunohistochemical staining (IHC),
and the phenotype of GLS was confirmed by in vivo experiments of subcutaneous tumor formation in mice and in vitro
experiments of functional biology, including Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry,
transwell migration, and Boyden invasion assay. Finally, it was also verified whether the treatment of NPC cells by
GLS inhibitor CB-839 can change various biological functions and protein expression to achieve the purpose of blocking
tumor progression.

Results:
GLS was remarkably overexpressed in NPC cells and tissues, predicting a poor overall survival of NPC patients.
GLS promoted cell cycle, proliferation, colony formation, migratory, and invasive capacities by regulating Cyclin
D2 (CCND2) via PI3K/AKT/mTOR pathway in NPC in vitro and in vivo. Notably, CB-839 showed an effective
anti-NPC tumor effect by blocking the biological functions of the tumor.

Conclusion:
The first innovative proof is that GLS promotes cell proliferation by regulating CCND2 via
PI3K/AKT/mTOR pathway in NPC, and GLS inhibitor CB-839 may serve as a new potential therapeutic target for
NPC treatment.
An Update on Herbal Products for the Management of Inflammatory
Bowel Disease
Authors: Arya Himanshu , Dass Rameshwar , Chopra Bhawna , Kriplani Priyanka , Deswal Geeta , Singh Grewal Ajmer , Dhingra Ashwani K. , Kumar Suresh 
Published: July 2023

Abstract:
Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn's Disease (CD), is a continuously increasing healthcare problem mainly characterized by chronic relapsing intestinal inflammation. The common symptoms of UC and CD include inflamma-tion, diarrhea, abdominal pain, bleeding, and weight loss. IBD is generally caused by an inter-action between genetic and environmental or microbial factors that influence the body's im-mune response and is responsible for digestive disorders and inflammation of the intestinal tract. However, a complete understanding of the pathophysiology and work-up of IBD is neces-sary to ensure appropriate treatment for the management of this complex disease. This review enlightens herbal therapeutics and drug delivery systems for the management of IBD, and thus provides new insights into this field and facilitates access to new treatments.
Tacrolimus and Cyclosporin Pharmacotherapy, Detection Methods,
Cytochrome P450 Enzymes after Heart Transplantation
Authors: Tolou-Ghamari Zahra 
Published: July 2023

Background:
Advances in organ transplantation were made after the discovery of the
pure form of cyclosporine by Dr Jean Borel in the 1970s. In fact, in clinical practice achieving a
delicate balance in circulating immunosuppressive necessitate focus on the difficult task of posttransplant
therapeutic drug monitoring.

Objective:
The purpose of this study was to determine the pharmacologic properties of cyclosporine-
tacrolimus, detection methods, and the effects on the activity of cytochrome P450 enzymes
when prescribing the most efficient treatments in forms of polypharmacy for the recipients of heart
transplantation.

Methods:
Scientific literature on the interactions of tacrolimus and cyclosporine with human cytochrome
P450 enzymes was searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/),
Web of Science, and Scopus.

Results:
Prescription immunosuppressive drugs based on polypharmacy accompanied by induction
agents could result in hidden neurotoxicity and nephrotoxicity. A literature search shows that
cyclosporine prescription with antihypertensives drugs needs close monitoring. Co-administration
of tacrolimus and diltiazem or verapamil needs a decrease in the tacrolimus dose by 20-50%. Vigilant
attention to the lowest possible statin dose is needed when coadministered with fluvastatin or
pravastatin. Polypharmacy based on ticlopidine, clopidogrel, and cyclosporine or tacrolimus needs
monitoring of immunosuppressive drug levels for several months. A prescription with clotrimazole
or fluconazole needs close monitoring, and itraconazole or ketoconazole needs to reduce the
initial dose by 50%. Combination with nefazodone needs to be avoided, and alternative drugs such
as sertraline or citalopram could be prescribed in addition to further monitoring consideration. In
prescription with phenytoin, the bound and free phenytoin levels need close monitoring.

Conclusion:
Polypharmacy based on tacrolimus or cyclosporine needs vigilant therapeutic drug
monitoring due to the cytochrome P450 enzymes associated with biochemical variables in metabolic
pathways. Further attention to polypharmacy should be given to circulate drugs that could
hide pharmacokinetics interactions associated with infections, malignancies, chronic kidney disease,
and rejection after organ transplantation.
Pendidikan karakter melalui karang taruna untuk membangun karakter sosial pada generasi digital native
Authors: Widiatmaka Pipit , Mujahidah Nelly , Rahmap Rahmap , Arifudin Arifudin 
Published: July 2023

Tujuan penelitian ini mendeskripsikan implementasi pendidikan karakter melalui kegiatan yang dilakukan di karang taruna yang berperan dalam membangun karakter sosial pada generasi digital native dan menganalisis kendala yang dihadapi karang taruna dalam membangun karakter sosial pada generasi digital native. Penelitian ini menggunakan pendekatan kualitatif dengan metode studi kasus. Pengumpulan data dalam penelitian ini melalui studi dokumen dan analisis data yang digunakan yaitu analisis deskriptif kualitatif. Hasil penelitian menunjukkan bahwa pendidikan karakter dapat diimplementasikan di karang taruna, yang merupakan wadah berkumpulnya generasi digital native untuk mengembangkan bakat dan keterampilannya. Peran karang taruna dalam membangun karakter sosial melalui berbagai kegitan seperti, gotong royong, kegiatan kerohanian, pembinaan dari pengurus, membantu masyarakat yang sedang mengalami kesulitan dan lain sebagainya. Kendala yang dihadapi oleh karang taruna dalam membangun karakter sosial generasi digital native yaitu partisipasi generasi ini mulai menurun karena teknologi internet, intervensi oknum yang memiliki kepentingan politik, dan kurangnya dukungan dari pemerintah khususnya pemerintah desa terhadap kegiatan yang diselenggarakan oleh karang taruna.The purpose of this study is to describe the implementation of character education through activities carried out in Karang Taruna (youth organization), that play a role in building social character in the digital native generation, and to analyze the obstacles faced by Karang Taruna in building social character in the digital native generation. This study uses a qualitative approach with a case study method. The data collection in this study is through document study and the data analysis used is descriptive qualitative analysis. The results of the study show that character education can be implemented in Karang Taruna, which is a gathering place for the digital native generation to develop their talents and skills. The role of Karang Taruna in building social character is through various activities such as mutual cooperation, spiritual activities, coaching from administrators, helping people experiencing difficulties, and so on. The obstacles faced by Karang Taruna in building the social character of the digital native generation is that the participation of this generation has begun to decline due to internet technology, the intervention of individuals with political interests, and the lack of support from the government, especially the village government, for activities organized by Karang Taruna in building social character is very effective through several activities
Degradasi moral siswa dalam penerapan nilai-nilai pancasila ditinjau
Authors: Revalina Atiqah , Moeis Isnarmi , Indrawadi Junaidi 
Published: July 2023

Penelitian ini bertujuan untuk menganalisis masalah degradasi moral siswa terkait penerapan nilai-nilai Pancasila ditinjau dari makna dan hakikat pendidikan kewarganegaraan (PKn) sebagai pendidikan karakter. Penelitian ini juga mendeskripsikan bentuk-bentuk degradasi moral siswa, faktor penyebab degradasi moral, dan implikasi degradasi moral dalam penerapan nilai-nilai Pancasila. Penelitian ini menggunakan pendekatan kualitatif dengan metode deskriptif. Data dikumpulkan melalui wawancara, observasi, dan studi dokumen. Hasil penelitian menunjukkan bahwa ada berbagai bentuk degradasi moral siswa dalam penerapan nilai-nilai Pancasila dan yang paling signifikan yaitu: penurunan nilai religius, penurunan nilai kemanusiaan, dan penurunan nilai persatuan. Faktor penyebab degradasi moral siswa yakni lemahnya pengetahuan dan paham nilai-nilai Pancasila, kelalaian orang tua dalam mendidik anak, dan pengaruh gadget atau media sosial. Implikasi dari degradasi moral siswa dalam penerapan nilai-nilai Pancasila, jika ditinjau dari makna dan hakikat PKn sebagai pendidikan karakter, yaitu tidak adanya perilaku yang mengindikasikan hubungan manusia dengan Tuhan, karakter peduli sosial terhadap hubungan hidup sesama manusia, karakter patriotisme dan kebersamaan, karakter demokratis dan adil bagi semua pihak tanpa pandang bulu. This study aims to analyze the problem of students’ moral degradation related to the application of Pancasila values in terms of the meaning and nature of civic education (PKn) as character education. This study also describes the forms of student moral degradation, the factors causing moral degradation, and the implications of moral degradation in the application of Pancasila values. The study uses a qualitative approach with descriptive method. Data was collected through interview, observation, and document study. The results of the study show that there are various forms of student moral degradation in the application of Pancasila values, and the most significant of which are: a decrease in religious valuess, a decrease in human values, and decrease in the values of unity. Factors causing student moral degradation are the lack of knowledge and understanding of Pancasila values, negligence of parents in educating children, and the influence of gadgets or social media. The implications of student moral degradation in applying Pancasila values, when viewed from the meaning and nature of civic education as character education, are namely the absence of behavior that indicates a human relationship with God, the character of social care for the living relationships of fellow human beings, the character of patriotism and togetherness, democratic character and fair to all parties indiscriminately.
EMPOWERING MAQĀṢID AL-SYARĪ‘AH
Authors: Sabil Jabbar 
Published: July 2023

Some contemporary Muslim scholars try to utilize maqāṣid as an istinbat method, including fiqh al-maqāṣid proposed by Yusuf al-Qaraḍawī and fiqh al-maṣāliḥ offered by Fatḥī al-Duraynī. Unfortunately, fiqh al-maqāṣid cannot be operated as a method because its character is axiology. In addition, the abstract nature of maqāṣid makes it not applicative, except as a moral guide. Therefore, Ibn 'Āsyūr proposed the discovery of maqāṣid at a specific level, namely maqāṣid al-syarī'at al-khāṣṣah. Meanwhile, fiqh al-maṣāliḥ also experiences problems because of its descriptive characteristics, even though the legal istinbat method demands prescriptive results. The solution for this problem is combining the two offerings and then integrating them into an istinbat methodology which is composed of two stages of research; the descriptive stage and the prescriptive stage. This method is built based on the means-end model (wasā'il-maqāṣid), where maqāṣid is the approach in it. This study uses philosophy as a method and epistemology as an approach.
LEGAL BASIS OF IMPOSING SANCTIONS ON ILLEGAL PARKING RETRIBUTION COLLECTORS FROM THE MAQĀṢID PERSPECTIVE
Authors: Isnawan T.M. Rianda 
Published: July 2023

The phenomenon of illegal parking fees in Banda Aceh City has caused public unrest. Unfortunately, the authorities cannot take action because there are no rules. In the context of the Sharia Law implementation in Aceh, the qanun (law) that enforces must have a basis of shar'ī sovereignty. Therefore, this study examines the legal basis for imposing sanctions on collectors of illegal parking fee from the perspective of maqāṣid al-sharīa. This study is a normative legal research that using the maqāṣidī approach. The researcher found that the City of Banda Aceh Qanun Number 4 of 2012 did not contain sanctions against collectors of illegal parking retribution, even though the collectors of illegal parking fees take advantage of this qanun. The researchers found that fake collectors must to punish because of acts of treason against the state. The legal basis is the specific purpose of the Shari'a (maqāṣid al-khāṣṣah) contained in verse 105 of Surah an-Nisa'. This study concludes that the government must not defend traitors, so government must impose sanctions.
A Congruous Model of Matrilineal Culture Inheritance
Authors: Firdaus Dwi Rini Sovia 
Published: July 2023

De Fleur's communication model inserts the mass media device, gives the possibility to two-way feedback, and stated that noise might occur at any stage. In contrast, the flowthing model introduced by Al-Fedaghi describes the information flow. This research adapts both concepts to produce cultural inheritance communication models. Minangkabau was chosen because of its unique matrilineal cultural pattern, where customary leaders take part in the wider family communication besides the role of the father and the mother. All concepts inculcate the soul of leadership, entrepreneurial spirit, and high social spirit. This answers the stereotype of Minangkabau people as hard-working entrepreneurs.
Konsep Pemikiran Ekonomi Dan Kebijakan Pasar Dalam Perspektif Yahya Bin Umar Dan Relevansinya Pada Sistem Ekonomi Modern
Authors: Suparno Suparno , Mukhlishin Ahmad 
Published: July 2023

This paper will explain the contribution of Yahya bin Umar's economic thinking regarding the role of the state in the economy in the market. Yahya bin Umar had contributed his thoughts in the 9th century AD. According to him, the role of the state in regulating the market and prices of goods was not very dominant, because the state intervened if in the mechanism of price of goods in the market experienced monopolistic practices such as ihtikar, cartels and hoarding of goods. So, the role of the state is indispensable for controlling prices and goods for the benefit and welfare of society. Keywords: thinking, market,,Ihtikar (hoarding of goods) Tasy'ir (pricing)
مفهوم الذات البدنية ودافعية الإنجاز وعلاقتهما بأداء مهارتي الخداع البسيط والتصويب من القفز عاليا ً بكرة اليد لدى طلبة جامعة الكوفة
Authors:   كلية التربية البدنية وعلوم الرياضة ، جامعة الكوفة ، العراق, Al Mawashi Ghassan , Abdulaziz Rehab Nabeel ,   كلية التربية البدنية وعلوم الرياضة ، جامعة الكوفة ، العراق, Abod Mustafa Alaa ,   كلية التربية البدنية وعلوم الرياضة ، جامعة الكوفة ، العراق
Published: July 2023

يرى الباحثون أن معرفة اللاعب أو الطالب لقدراته البدنيه ومستواه المهاري تؤثر وبشكل كبير على نجاحه في تنفيذ المهام الموكله به سواء كان ذلك في الدرس أو في ممارسته لأي فعالية يهتم بها. وقد أكدت الكثير من الدراسات على أهمية العلاقة بين مفهوم الذات ودافعية الانجاز والأداء الفني أو المهاري علاقة طردية اي انه اذا كان مفهوم الطالب عن ذاته جيدا او ايجابيا فان أداءه هو الاخر جيد وايجابي. لذا فإن فهم الطالب لذاته البدنيه ومستوى دافعيته يسهمان بشكل كبير في تحسين أداء المهارات ، لذا اختار الباحثون أن يخوضو غمار معرفة مدى تأثير متغيري مفهوم الذات البدنيه ومستوى الدافعية على تعلم وأداء مهارتي التصويب من القفز عاليا ً والخداع البسيط لطلبة المرحلة الرابعة في كلية التربية البدنيه وعلوم الرياضة جامعة الكوفة .	وقد هدف البحث الى : التعرف على مستويات متغيري مفهوم الذات البدنيه ودافعية الانجاز ومهارتي الخداع البسيط والتصويب من القفز عاليا ً وما هي العلاقة بين هذه المتغيرات لدى طلبة المرحلة الرابعة.	واستخدم الباحثون المنهج الوصفي وبالأسلوب المسحي (العلاقات الارتباطية), وقد حدد مجتمع الدراسة بطلاب المرحلة الرابعة لكلية التربية البدنيه وعلوم الرياضة / جامعة الكوفة ، للعام الدراسي 2021-2022 والبالغ عددهم (117) طالباً , وتم اختيار عينة منهم بالطريقة العشوائية البسيطة بواقع (80) طالباً , وتم تقسيمهم الى عينتين الاولى العينة الاستطلاعية وبعدد (20) طلاب والثانية عينة التطبيق وبعدد (60) طالب وبواقع (30) طالب من كل شعبة يصبح مجموع العينة الكلي (80), وبعد الانتهاء من تطبيق المقاييس والاختبارات الخاصة بمتغيرات البحث ، قام الباحثون بجمع البيانات وتمت معالجتها إحصائياً ببرنامج (spss).	أما عن أهم الإستنتاجات فهي: أن مفهوم الذات البدنيه للطلبة من أهم المتغيرات التي يجب الاعتماد عليها في اتقان تعلم وأداء المهارات ، وذلك للوقوف في نقطة شروع واحدة للبدء في عملية التعليم من قبل المدرس . تكون الدافعية لتحقيق الانجاز مبينة على أساس الفهم الحقيقي لمعرفة الطالب لقدراته الجسدية ، فلا يمكن أداء مهارة معينة فوق مستوى الطالب وهو يعلم ذلك دون التدريب عليها. للمهارات الأساسية بكرة اليد طابع خاص تحتاج إلى إدراك كبير من الطالب لقدراته ورفع دافعيته للإنجاز قبل الشروع في تعلم أي مهارة جديدة ومركبة.	أما عن أهم التوصيات فهي: يجب أن يفهم الطالب ذاته البدنيه كي تؤهله لكيفية أداء المهارات الرياضية حسب امكاناته . يجب تحسين مستويات الدافعية للطلاب لما لها من أثر على أداء المهارات الحركية وتحقيق الانجاز