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Evaluating the Indigenous Probiotic Lactococcus lactis D4 as an Adjuvant to Capecitabine: Modulation of NF-κB in a Colorectal Carcinogenesis Model Arli Suryawinata; M Iqbal Rivai; Rini Suswita; Irwan; Avit Suchitra; Raflis Rustam
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i5.1572

Abstract

Background: Chronic inflammation driven by the nuclear factor kappa-B (NF-κB) signaling pathway is a fundamental driver of colorectal cancer (CRC) pathogenesis, promoting tumor survival, mucosal proliferation, and profound chemoresistance. Capecitabine is a standard first-line fluoropyrimidine chemotherapy; however, its clinical utility is frequently compromised by dose-limiting toxicities and the activation of inflammatory feedback loops. Lactococcus lactis D4, a novel probiotic strain isolated from traditional Indonesian fermented buffalo milk (dadih), possesses well-documented immunomodulatory properties. Methods: A randomized controlled experimental study was conducted utilizing male Sprague-Dawley rats (n=37). Colorectal carcinogenesis was chemically induced via intraperitoneal administration of 1,2-dimethylhydrazine (DMH). Following strict histopathological confirmation of malignancy, the cohort was randomized into five distinct groups: Negative Control, Positive Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Interventions were administered daily for 14 days. Outcomes included NF-κB protein expression assessed via immunohistochemistry (IHC) and targeted gene expression quantification via RT-qPCR. Results: Immunohistochemical analysis demonstrated that the positive control group exhibited significantly elevated NF-κB protein expression (35.87 ± 13.53%). Capecitabine monotherapy significantly reduced this expression to 16.07 ± 3.79% (p=0.003). The Combination therapy achieved a profound reduction in NF-κB protein expression down to 12.99 ± 4.92%; however, this was not statistically superior to Capecitabine alone (p=1.000). Conversely, RT-qPCR analysis revealed no statistically significant difference in NF-κB mRNA levels among the experimental groups (p=0.094). Conclusion: The combination of L. lactis D4 and Capecitabine effectively reduces NF-κB protein expression in a preclinical CRC model, achieving suppression levels comparable to primary chemotherapy. The distinct discordance between the significant protein suppression and the sustained mRNA expression levels suggests potential post-transcriptional or post-translational regulatory mechanisms that warrant further targeted molecular investigation.
Latihan Range of Motion sebagai Intervensi Keperawatan dalam Peningkatan Kekuatan Otot Pasien Stroke: Literature Review Oktaviani; Akbar Nur; Rita Ningsih; Sumarli; Irwan
Journal Kiara : Nursing and Midwifery Vol. 2 No. 1 (2025): Journal Kiara : Nursing and Midwifery - Advancing Sustainability Future Nursing
Publisher : Journal Kiara : Nursing and Midwifery

Show Abstract | Download Original | Original Source | Check in Google Scholar

Abstract

Latar Belakang: Stroke merupakan gangguan neurologis akibat gangguan suplai darah ke otak yang sering menimbulkan hemiparesis dan penurunan kekuatan otot. Rehabilitasi dini melalui latihan Range of Motion (ROM) menjadi salah satu intervensi non-farmakologis yang direkomendasikan untuk mencegah komplikasi dan meningkatkan fungsi motorik pasien. Tujuan: Menelaah dan menganalisis bukti ilmiah mengenai efektivitas latihan ROM terhadap peningkatan kekuatan otot pada pasien stroke. Metode: Penelitian ini merupakan literature review dengan penelusuran artikel pada database elektronik seperti PubMed, Scopus, ProQuest, CINAHL, dan ScienceDirect menggunakan kata kunci: stroke, range of motion, dan muscle strength. Kriteria inklusi meliputi artikel tahun 2016–2020, desain quasi-eksperimental, systematic review, dan studi observasional yang menilai kekuatan otot sebelum dan sesudah intervensi ROM. Sebanyak 15 artikel memenuhi kriteria dan dianalisis secara deskriptif. Hasil: Sebagian besar studi (n=10) menggunakan desain quasi-eksperimental dan menunjukkan peningkatan signifikan kekuatan otot setelah latihan ROM (p<0,05). Sebanyak 11 artikel membahas ROM aktif dan 4 artikel ROM pasif. Latihan dilakukan 2 kali sehari selama 15–35 menit dengan durasi intervensi minimal 4 minggu. Instrumen yang umum digunakan adalah Manual Muscle Testing (MMT) dan handgrip dynamometer. Kesimpulan: Latihan ROM, baik aktif maupun pasif, efektif meningkatkan kekuatan otot pada pasien stroke dan direkomendasikan sebagai bagian dari program rehabilitasi keperawatan berbasis bukti.
Synergistic Attenuation of the TNF-α/NF-κB Inflammatory Axis in Colorectal Carcinogenesis: Lactococcus lactis D4 as a Mucosal-Protective Adjuvant to Capecitabine Leonard Khriestsandi Saleh; M Iqbal Rivai; Rini Suswita; Irwan; Avit Suchitra
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 4 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i4.1571

Abstract

Background: Capecitabine serves as a standard chemotherapeutic agent for colorectal cancer, but its clinical efficacy is frequently hindered by severe gastrointestinal toxicity and incomplete suppression of the inflammatory tumor microenvironment. We evaluated the synergistic potential of Lactococcus lactis D4, a probiotic strain isolated from traditional fermented buffalo milk, as an immunonutritional adjuvant to Capecitabine in a 1,2-dimethylhydrazine-induced colorectal cancer rat model. Methods: Sprague-Dawley rats were maintained on a standardized AIN-93G diet and induced with 1,2-dimethylhydrazine. Animals were randomized into Negative Control, Cancer Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Treatments were administered for 14 days. We assessed cachexia, macroscopic microadenoma multiplicity, and TNF-α expression utilizing immunohistochemistry. Synergy was mathematically validated using the Coefficient of Drug Interaction. Results: The Combination group significantly prevented chemotherapy-induced cachexia, demonstrating a 2.1% weight gain compared to a 4.5% weight loss in the Capecitabine monotherapy group (p < 0.05). Macroscopic microadenomas were rapidly reduced in the combination group. Furthermore, the combination therapy synergistically suppressed colonic TNF-α protein expression (Coefficient of Drug Interaction = 0.83). Additionally, L. lactis D4 entirely mitigated capecitabine-induced mucositis. Conclusion: L. lactis D4 functions as a highly potent adjuvant to Capecitabine. It prevents cachexia, protects mucosal architecture, and exerts a mathematically proven synergistic suppression of the TNF-α inflammatory axis.
Evaluating the Indigenous Probiotic Lactococcus lactis D4 as an Adjuvant to Capecitabine: Modulation of NF-κB in a Colorectal Carcinogenesis Model Arli Suryawinata; M Iqbal Rivai; Rini Suswita; Irwan; Avit Suchitra; Raflis Rustam
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i5.1572

Abstract

Background: Chronic inflammation driven by the nuclear factor kappa-B (NF-κB) signaling pathway is a fundamental driver of colorectal cancer (CRC) pathogenesis, promoting tumor survival, mucosal proliferation, and profound chemoresistance. Capecitabine is a standard first-line fluoropyrimidine chemotherapy; however, its clinical utility is frequently compromised by dose-limiting toxicities and the activation of inflammatory feedback loops. Lactococcus lactis D4, a novel probiotic strain isolated from traditional Indonesian fermented buffalo milk (dadih), possesses well-documented immunomodulatory properties. Methods: A randomized controlled experimental study was conducted utilizing male Sprague-Dawley rats (n=37). Colorectal carcinogenesis was chemically induced via intraperitoneal administration of 1,2-dimethylhydrazine (DMH). Following strict histopathological confirmation of malignancy, the cohort was randomized into five distinct groups: Negative Control, Positive Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Interventions were administered daily for 14 days. Outcomes included NF-κB protein expression assessed via immunohistochemistry (IHC) and targeted gene expression quantification via RT-qPCR. Results: Immunohistochemical analysis demonstrated that the positive control group exhibited significantly elevated NF-κB protein expression (35.87 ± 13.53%). Capecitabine monotherapy significantly reduced this expression to 16.07 ± 3.79% (p=0.003). The Combination therapy achieved a profound reduction in NF-κB protein expression down to 12.99 ± 4.92%; however, this was not statistically superior to Capecitabine alone (p=1.000). Conversely, RT-qPCR analysis revealed no statistically significant difference in NF-κB mRNA levels among the experimental groups (p=0.094). Conclusion: The combination of L. lactis D4 and Capecitabine effectively reduces NF-κB protein expression in a preclinical CRC model, achieving suppression levels comparable to primary chemotherapy. The distinct discordance between the significant protein suppression and the sustained mRNA expression levels suggests potential post-transcriptional or post-translational regulatory mechanisms that warrant further targeted molecular investigation.
IMPLEMENTATION OF ISSUANCE OF LAND TITLE CERTIFICATES IN PEAT AREAS IN PEKANBARU CITY Irwan; Harahap, Irawan; Libra, Robert
JILPR Journal Indonesia Law and Policy Review Vol. 7 No. 2 (2026): Journal Indonesia Law and Policy Review (JILPR), February 2026
Publisher : International Peneliti Ekonomi, Sosial dan Teknologi

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.56371/jirpl.v7i2.592

Abstract

Land certificates are expected to guarantee legal certainty, protect community rights, while still paying attention to the ecological function of peat as part of the environment. The purpose of this study is to analyze the implementation, obstacles, and efforts to overcome obstacles in the issuance of land title certificates in peat areas in Pekanbaru City. The method used is sociological legal research. Based on the results of the study, it is known that the implementation of the issuance of land title certificates in peat areas in Pekanbaru City has not been carried out optimally, because the issuance of land title certificates in peat areas also has the potential to cause conflicts between the legal certainty of land rights and the interests of protecting the peat ecosystem if not accompanied by strict spatial use controls. Therefore, land certification in peat areas cannot be interpreted solely as legalization of land ownership, but must be placed within a conditional legal framework that takes into account the social function of land and environmental sustainability. Obstacles are complex and multidimensional in nature, including the unclear status and function of peat areas, which requires caution from land officials to avoid conflict with spatial planning and environmental protection provisions. Furthermore, the unstable physical condition of peatland causes difficulties in measuring and establishing boundaries, thus slowing the technical certification process. From an administrative and legal perspective, weak land rights, poorly documented land ownership histories, and overlapping land ownership claims are still common. This is exacerbated by the lengthy coordination process between agencies. Meanwhile, from the community perspective, obstacles also arise from a lack of understanding of land and environmental law, as well as minimal outreach and assistance, often making it difficult for applicants to meet the stipulated requirements.
Co-Authors AA Sudharmawan, AA Abdul Azis Abdul Jabbar Abdul Jalil Abdurahman Abdurrahman Acoci Adi Hermawan Adi Sumandiyar Adiatma Adnan Sauddin Agahirber Agustinus Bayu Suseno Ahmad Muktamar B Ahmad Safran Ahmad Syahird Ahmad Syahird ahmad yani Ahmad Zaki Ahmad Zikir Ahmad, Regina Maharani H. Ahmadin Ahmed J. Obaid Aidi, Khasnatul Akbar Iskandar Akbar Nur Akbar, Azaz Akhsan Akhwan Ali Aksan, Muhammad Ali, Lalu Usman Ali, Nur Fitriana Muhammad Alimbran, Fadhilah Adawiyyah Alimuddin Aliza, Nur Alparisi, Bima Diokta Amalia, Nindy Putri Aman Ma’arij Amanda Sari, Dina Amanda, Samira Ami Pratama Ananda, M. Dea Putra Ananda, M.Riski Anang Arya N Anasrudin Andi Asmawati AR Andi Mutiah Sari Andi Rizal Andi Uceng Andinata, Muhammad Pebri Anhar Anita Kaimuddin Anwar, Rydho Apriyani, Ika Ardaniansyah Arham Rusli, Arham Ariesta Ariyansah, Febri Arli Suryawinata Ashari, Asty Asmira Asmi Citra Malina, Asmi Citra Asniwati Asran, Asran Asri Asri Asriza, Muhammad Arif Auliah Ambarwati Avit Suchitra Ayu Rofia Nurfadillah Ayumar, Andi Azaz Akbar Azwani Lubis B, Sofyan Badaruddin Badrus Zaman, Akhmad Roja Baiq Nurkhalishah Bakri, Faldi Barany Fachri Basir Benti Yulius, Benti Catur Budi Wicaksono Chaliluddin Christin Mellenia Dahruji Damara, Dedy Darja, Rahma Darmeli Nasution Davy Anggara Saragih, Muhammad de Lima, Filda Vionita Irene Deddy Saputra Dedi Fazriansyah Putra Dedy Rahmad Sitinjak Delfi Enida Deswita Deswita Dewi, Andi Ratna Sari Dhea Setyaningsih Putri Dikky Mooy Djohar Eka Desy Purnama Eka Putra Elisa Dwi Irvina Elpira Asmin Elvawati Ernawita Erwinsyah Eti Yerizel F, Annisa Maida Fachri, Barany Fahira, Raihan Fahmi Arfan Fajar Ryanda Falah, Nurul Fatrina M. Gani Fedrianus Korintius Lektawan FERY ARDIANSYAH Fifi Alfirah Fiisyatin Rodiah Firhansyah Fikri Khair Fitri Fitriani Fitriyanti Kasim Fransisca, Amanda Fransiskus Heryman Surya Gadur Gajah, Sufi Maulana Gunawan Abdul Wahab Haeruddin Syarifuddin Hafni Hajerah Hamdi Handayani, Mita Puri Haq Hataul, Is Asma'ul Harahap, Irawan Hardianto Ramadhan Hartoto Haryadi HB, Erlina Helena, Shifa Helman Hendra HENDRA SETIAWAN Hendry . Herman, Daniel Herry Sonjaya Hery Winoto TJ Hukiyanto, Hudan Ibrahim, Nur Wahyuningsih Ichsan Setiawan Ilham Akbar Ilham Zulfahmi imran saputra Inah Mutmainna Indra Sabdarudin Indradewa, Rhian Irwan Amar Irwan Surya Darmawan Irwan, Muh. Ismarica Iswandi J. Kalatasik, S.Si, Arniati Ja'faruddin Jaelani Jafri, Dafa Umar Jaidan Jaja Miharja Jannah, Khusnul Ja’faruddin Jetro Sihombing Johamran Pransisto Jufri Jumriana Junaid, Ninis Ramadhani Junaidi M. Affan K, Muh. Arif Rezki Ananda Kailola, Nathalie Kamarudin Kamarudin Karlina Bte Muhammad Kartini, Siti Agus Kasma, Andi Yulia Kasman Ediputra Khadijah , Ummul Khaerul Kholidi, Ahmad Khairunnas Khumairoh, Annisa Kittisak Wongmahesak Krisnawati Kusuma, Jaya L, Syahrir Lakoro, Rezha Rafsanjani Latief, Rahmi R. Latuconsina, Vina Zakiah Leonard Khriestsandi Saleh Libra, Robert Liedeman Lola Lubis, Akhyar Lucky Hartanti, Lucky Luthfita Datau M Iqbal Rivai M Ridwan Yunus M. Chaisar M. Ihsan M. Iqbal Rivai M. Yunus Madison Mahmud Mustapa Maila, Siti Maila Faiza Tanjung Mallolongeng, Fitrah Manan Mansyur Margaretha, Solang Marianus Dinata Alnija Marlina, Triya Mawar Jingga Ing Purwani Mayurni Firdayana Malik Megawati Mei Indra Jayanti Melani Koniyo Meliala, Sofian Sauri Milhan Minsas, Sukal Moch. Syauki Moh. Rivai Nakoe Mohamad Sutrisno Mohammad Tasyrik Zakaria Monalisa Ibrahim Mooy, Hersi Marthalitha Muh Irwan Muh. Irwan Muh. Rusdi Muh. Tamrin Muhaemin Muhajir Muhajir, Muhajir Muhamad Habib Muhammad Muhammad Amri Amin Muhammad Ikhsan Muhammad Iqbal Nugraha Muhammad Isbar Pratama Muhammad Muhadir Aludin Muhammad Rais Rahmat Muhammad Rizki Muhammad Rusdi Muhammad Zen, Muhammad Muhjria Muslim Musnar Indra Daulay Mustafa Parinduri Mustanir, Ahmad Nadia Azzahra Naifa Naila, Aisya Nailah, Dea Anjani Nasaruddin Nasrullah Nasution, Fikri Haikal Fadly Nini Andriani Nofridayati Nur Fikriyah, Aisyah Nur Ida Nur Wahida , Zam Nurahmayanti, Annisa Nurani, Kahvi Nurazizah Nurfadilah, Khalilah Nurfazlin Nova Nurhasanah Nurlatipah, Diah Nurrahmayanti, Annisa Nursyirwan Nurwijayanti Oktaviani PANDI FIRMAN Pandjajangi, Andi Muhammad Ridho Yusuf Sainon Andi Parlindungan Banjarnahor Parman Prabowo, Humam Eddy Pradeva Zebua, Yan Fitra Pratiwi, Leny Pratiwi, Puteri Ayu Priscilla Beverly Putri Putri Utami Putri, Ariella Ramadhani Putri, Arina Putri, Fatia Aisyah Rabukit Rachmawati Dwi Agustin Raflis Rustam Rahanra, Sartika Riry Rahman, Muhammad Fathur Rahman, Rahmaniar Rahmat Makmur Rahmat R, Muh. Faisal Rahmawati Rakhmat Wahyudin Sagala, Rakhmat Wahyudin Ramadhani Kirana Putra Ramly Abudi Rangkuti, Rahmadsyah Rasdianah Ratisa Razali Thaib Restu Nur Hasanah Haris Revalina, Atiqah Rezky Dwi Fitriani Ricky Ramadhan Harahap Rika Fitriani Rini Malau Risnawati Ibnas Rita Ningsih Rizal, Chairul Rizky Amelia Rosalinda Rosidah Rr. Dian Anggraeni Rudi Rudi Arafah Rusmin Nuryadin Rustam, Ilmi Nurfaizah Rustim Sabila, Puji Chairu Sadam Husen Saifullah Salam, Agus Salikim Samritin Santi Anwar Santi Niati SAP, Andi Muh. Ridho Yusuf Saptino Miro, Saptino Sari, Eka Rosmitha Sariani, Dona Sayyid Afdhal El Rahimi Sekha Anggita Maulidina Sella Mawarni Sellang, Kamaruddin Sembe, Imanuel Agung Sepmiko, Jorza Setiawan, Eka Shaleh, Muhammad Sidjara, Sahlan Sihombing, Hubertus L. SRI RAHAYU Sri Rahmadani Sri Wira Utami Sriwati Sriwati Sudariyah Sulaiman Sumarli Sunarso Suparno, Antoni Supiyandi Supiyandi Surahman, Suryansyah Susanto Wibowo Suswita, Rini Suwardi Annas Suyanto Syafrizal Nasution Syafruddin Side Syahirah, Nurul Syarif Hidayat Syarifuddin Syauket, Amalia Syukri, Khairiadi Tahirah Hasan Talamoa, Moh Fauzan Tanjung, Aulia Rachman Teguh Hilmansyah Thaib Rizwan Tiara Amelia Tohap Pandapotan Simaremare Tri Indah Rezeki, Tri Indah Tri Septian Maksum Tua Natalis Situmorang, Marningot Tullah, Muh. Firdaus Ulfa Aulia Ulfa, Maryam Umar Umar P Ummiati Rahmah Usman Mulbar USWATUN HASANAH Utami, Sri Wira vido valentino Wa Ode Masrida Wahidah Sanusi Wahyuni, Maya Sari Waode, Yully Sofyah Warsidah, Warsidah Wathan, M.Hizbul Wicaksono, A. Dharmawan Wiwin WIWIN SEPTIADI Wotu, Asma H.J Yang Agita Rindri Yanti, Nur Eva Yenti Arsini Yerizon Yesi Yohanes Mardinata Rusli, Yohanes Mardinata Yugatama, Andyan Yuliana, Fika Yusfi Hasanah Yusnan, Muhammad Yusnelli Yusran Yusran, Andi Muhammad Fauzan Shadiq Yusri Dianne Jurnalis Yusril, Muh. Yustini Alioes Zahra, Nora Auliya Zuhri Zulfitra, Muhammad