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Possible Role of Akt in Mossy Fiber Sprouting: Akt Activity and CA3 Mossy Fiber Sprouting in a Kainate Model of Epilepsy: Akt Activity and CA3 Mossy Fiber Sprouting in Epilepsy husna, Machlusil; Handono, Kusworini; Sujuti, Hidayat; Aulanni'am, Aulanni'am
Journal of Tropical Life Science Vol. 14 No. 3 (2024)
Publisher : Journal of Tropical Life Science

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.11594/jtls.14.03.09

Abstract

The most prevalent pathological phenomenon observed in patients with epilepsy is hippocampal mossy fiber sprouting (MFS), which is thought to be associated with epileptic progression, such as worsening seizure control, cognitive function, and behavior. MFS is discovered in the dentate gyrus and the hippocampal Cornu Ammon 3 (CA3) area. The CA3 area is involved in memory, so disturbances in that area can affect memory impairment in patients with epilepsy. The mammalian target of rapamycin complex-1 (mTORC1) is also associated with MFS. Akt is an upstream activator of mTORC1 and a downstream target of mammalian target of rapamycin complex-2 (mTORC2) and plays a role in cytoskeleton organization. We analyzed Akt activity and MFS in the CA3 zone in an in vitro model of kainate-induced epilepsy. We divided organotypic hippocampal slice cultures (OHSCs) into a kainate (epilepsy) group and a control (untreated) group. On the 10th day in vitro (DIV), the kainate group was exposed to 8 µM kainic acid for 48 h, diluted in the medium. At 32 DIV, we measured Akt activity through western blotting and CA3 MFS through synaptoporin fluorescence intensity observed using confocal laser scanning microscopy. We found that Akt activity increased significantly (p = 0.000) in the kainate group, and the synaptoporin fluorescence intensity also increased in the stratum oriens of the CA3 area (p = 0.049) in the kainate group. Our findings implied that Akt may play a role in MFS development. Because Akt is a main downstream target of mTORC2, mTORC2 may also be involved in MFS development. Further research is required to clarify these findings.
Association of clinical manifestations, disease activity, and medications on premature atherosclerosis in systemic lupus erythematosus Pratama, Mirza Zaka; Kusworini Handono; Cesarius Singgih Wahono; Ahmad Bayhaqi Nasir Aslam; Syahrul Chilmi
Heart Science Journal Vol. 6 No. 1 (2025): Challenges in Managing Acute Heart Failure
Publisher : Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.hsj.2025.006.01.11

Abstract

Background SLE is distinguished by the development of multiple autoantibodies that lead to chronic inflammation and increased risk of cardiovascular diseases, especially atherosclerosis. Objective This examination sought to explore the association between the disease activity, clinical manifestations, and medication with the atherosclerotic lesion from SLE patients. Methods This inquiry investigated forty-two female SLE patients (18-45 years old) who met the 2019 EULAR/ACR assortment decency with matched healthy individuals as control A cross-sectional study was sanctioned at the Rheumatology Clinic of Saiful Anwar General Hospital Malang between July and November 2023. Demographic data, clinical manifestations, and medication history was documented in the medical records. Disease activity was stelled by the SLEDAI-2K score. Carotid Intima-Media Thickness (cIMT) and Flow-Mediated Dilation (FMD) (after brachial BP cuff inflation up to 200 mmHg for five minutes) examinations were used as atherosclerosis marker. Results Markedly higher of cIMT mean was demonstrated in SLE patients compared to healthy individual (0.51±0.11 vs 0.40±0.11 mm, p<0.001). FMD was subtancially curtailed in SLE patients set side to side to control (0.00 (0.00-0.10) vs 0.10 (0.00-0.28) mm, p=0.022). There was no statistical distinctness of the cIMT and FMD among SLE patients according to the presence of clinical manifestations. Neither cIMT nor FMD showed a statistically correlated with the disease activity. Patients who received hydroxychloroquine (0.57±0.02 vs. 0.50±0.09 mm, p=0.043) and cyclophosphamide (0.55±0.09 vs. 0.48 ± 0.10 mm, p=0.031) had higher cIMT. Higher cIMT was demonstrated in subjects who received steroid (p=0.045) and the dosage of steroid was essentially enforced to cIMT (R=0.418, p=0.034). Conclusion Our study unveil that early atherosclerosis was evidenced in patients with SLE and several medications might affect the progressivity of atherosclerosis.
Menurunkan Angka Kejadian dan Mencegah Kekambuhan COVID-19, Lupus, Reumatik, dan Alergi Melalui Pembentukan Desa Binaan Dewi, Elvira Sari; Wahono, Cesarius Singgih; Barlianto, Wisnu; Handono, Kusworini; Sari, Tita Luthfia; Hasanah, Dian; Rahman, Perdana Aditya; Anshory, Muhammad; Wulandari, Desy; Sari, Dewi Purnama; Endharti, Agustina Tri; Nurdiana, Nurdiana; Kalsum, Umi; Susianti, Hani; Kalim, Handono
International Journal of Community Service Learning Vol. 5 No. 1 (2021): February 2021
Publisher : Universitas Pendidikan Ganesha

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (189.075 KB) | DOI: 10.23887/ijcsl.v5i1.30161

Abstract

Kurangnya pengetahuan masyarakat tentang COVID-19, lupus, reumatik, dan alergi mempengaruhi keberhasilan terapi, penurunan angka kejadian, dan pencegahan kekambuhan. Tujuan pengabdian masyarakat adalah membangun desa-desa binaan tanggap COVID-19, lupus, reumatik, dan alergi di Malang oleh Tim Kelompok Kajian Lupus, Autoimun, Reumatik, dan Alergi (LAURA) Universitas Brawijaya. Warga desa binaan diberikan penyuluhan berupa seminar awam dan pelatihan tentang pertolongan awal pada penyakit COVID-19, lupus, reumatik, dan alergi, kemudian diminta mengisi kuesioner posttest untuk mengukur pemahaman. Desa-desa binaan diberikan thermo-gun dan wastafel untuk menerapkan protokol kesehatan. Satu bulan kemudian dievaluasi adanya kejadian COVID-19, lupus, reumatik, dan alergi di desa binaan. Hasil evaluasi menunjukkan rata-rata warga desa binaan memahami 78,3% materi yang diberikan dan menerapkan protokol kesehatan sesuai yang diajarkan saat penyuluhan. Dilaporkan tidak ada kejadian COVID-19 serta kekambuhan lupus, reumatik, dan alergi dalam satu bulan terakhir kegiatan. Kesimpulan: pembangunan desa-desa binaan di Malang meningkatkan tanggap warga terhadap COVID-19, lupus, reumatik, dan alergi.
Exploring Knowledge Gaps in Systemic Lupus Erythematosus Among Pre-Clinical Students and Junior Doctors in Medical Faculty Pratama, Mirza Zaka; Rahman, Perdana Aditya; Wahono, Cesarius Singgih; Handono, Kusworini
CoMPHI Journal: Community Medicine and Public Health of Indonesia Journal Vol. 6 No. 1 (2025): June
Publisher : Perhimpunan Dokter Kedokteran Komunitas dan Kesehatan Masyarakat Indonesia (PDK3MI)

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

Abstract

Understanding knowledge gaps is essential for developing more effective educational interventions that can bridge theory and practice. This study aimed to evaluate knowledge gaps in Systemic Lupus Erythematosus between pre-clinical students and junior doctors at a medical faculty. A cross-sectional study was conducted with 250 participants, divided equally between pre-clinical students and junior doctors (N=125 each). Variables such as gender, educational year, GPA, and study time were analyzed. Knowledge was assessed in five domains: pathophysiology, clinical manifestations, diagnosis, treatment, and complications. Linear regression analysis was used to identify factors associated with mean knowledge scores. No significant differences in gender distribution or study time (p = 0.899, p = 0.633, respectively). However, GPA scores were significantly higher among junior doctors (p < 0.001). Pre-clinical students scored higher than junior doctors in all SLE-related domains. GPA and study time were the strongest predictors of higher scores (Beta = 0.917, p < 0.001; Beta = 0.261, p < 0.001). GPA and study time significantly contributed to SLE knowledge scores, while gender and educational year did not. These findings suggest that academic performance and consistent study habits play critical roles in mastering SLE concepts among medical trainees.
Nano Liposomal Curcumin as an Adjuvant: Enhancing Cisplatin Anticancer Effects in HeLa Cells Subandi, Subandi; Balindra, Fredlina Rossa; Gizta, Aura Bella; Khotimah, Husnul; Handono, Kusworini
Sciences of Pharmacy Volume 4 Issue 2
Publisher : ETFLIN Publishing House

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.58920/sciphar0402347

Abstract

Cervical cancer, mainly driven by oncogenic HPV infections, remains a global health burden. Cisplatin is standard chemotherapy for advanced cases but is limited by toxicity. Nano liposomal curcumin, with improved bioavailability, may enhance cisplatin’s efficacy. This study investigated the combination’s effect on HeLa cells by analyzing Cyclin E1 and Bcl-2 expression. Nano liposomal curcumin was synthesized using thin-film hydration, yielding stable 32 nm nanoparticles. HeLa cells were divided into control and treatment groups, and varying doses of nano liposomal curcumin with cisplatin were received. Flow cytometry revealed significant reductions in Cyclin E1 (from 18.62 ± 1.45 to 5.79 ± 0.47) and Bcl-2 (from 32.56 ± 0.82 to 28.19 ± 0.30) at the highest dose (p < 0.05). Cell viability decreased to 9% with cisplatin alone and 1% with the combination. These results indicate that nano liposomal curcumin enhances cisplatin’s antiproliferative and pro-apoptotic effects, supporting its potential as an adjuvant to lower cisplatin doses while maintaining efficacy. Further research involving additional molecular markers, in vivo models, and clinical trials is needed to optimize dosing, confirm safety, and evaluate therapeutic potential.
A Synergistic Approach: Enhanced Apoptotic and Proliferative Inhibition of Cisplatin by Nanocurcumin in HeLa Cells Subandi, Subandi; Gizta, Aura Bella; Balindra, Fredlina Rossa; Handono, Kusworini; Khotimah, Husnul
Journal of Food and Pharmaceutical Sciences Vol 13, No 2 (2025): J.Food.Pharm.Sci
Publisher : Integrated Research and Testing Laboratory (LPPT) Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/jfps.21389

Abstract

Cisplatin is a widely used chemotherapeutic agent for cervical cancer, but its effectiveness is often limited by cellular resistance and severe side effects. Curcumin has demonstrated potential to enhance cisplatin's anticancer effects by inducing apoptosis and inhibiting cell proliferation; however, its clinical use is constrained by poor solubility and low bioavailability. To overcome these limitations, liposomal nanocurcumin was developed. This study aimed to evaluate the synergistic effects of cisplatin and nanocurcumin on Bax and BrdU expression as markers of apoptosis and proliferation in HeLa cervical cancer cells. A true experimental post-test only design was employed with five groups: HeLa cell control (no treatment), positive control (cisplatin 5 µg/mL), and three treatment groups receiving cisplatin 2.5 µg/mL combined with nanocurcumin at 25, 50, and 100 µg/mL. Cells were incubated for 48 hours and analyzedusing flow cytometry. The combination treatment significantly increased Bax expression and reduced BrdU expression compared to cisplatin alone, with the strongest effect observed at 100 µg/mL nanocurcumin. These findings suggest that nanocurcumin may serve as a promising adjuvant to enhance the therapeutic efficacy of cisplatin by promoting apoptosis and suppressing proliferation in cervical cancer cells.
Performance of Soluble CD28 and CTLA4 as a Potential Marker of Immunosenescence Pratama, Mirza Zaka; Handono, Kusworini; Poetri, Levrita Nindya; Maghfirah, Halimi Bidaimi
Clinical and Research Journal in Internal Medicine Vol. 6 No. 1 (2025): Volume 6 No 1, May 2025
Publisher : Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.mrj.2025.006.01.05

Abstract

Background: Immunosenescence is a condition of decreased function of the immune system that is generally found in elderly individuals. Several costimulatory molecules, such as CD28 and CTLA-4 have been investigated for their essential role in the immune aging process. Aim: This study aimed to determine the role of the soluble costimulatory molecules in immunosenescence. Methods: This study was observational research with cross-sectional approach. Samples were tested using ELISA and flow cytometry examination. Statistical analysis was conducted using independent T-test or Kruskal-Wallis comparison test. Correlation between each biomarker was determined with Pearson or Spearman correlation test. Diagnostic performances of each biomarked were assessed using ROC curve. Results: This study involved 52 subjects, of which 20 were young individuals aged between 20 to 28 years and 32 were elderly individuals aged between 60 to 85 years. In this study we found that CD4CD28+ and CD8CD28+ T cells were lower in elderly group (p<0.001), while CD4CD57+ and CD8CD57+ T cells were higher in elderly group (p<0.001). sCD28 and sCTLA-4 were significantly higher (p 0.039 and p 0.025 respectively) in old individuals than in young individuals. CD8CD28+ and sCD28 exhibit a significant negative moderate correlation (p=0.007, r= -0.368) meanwhile sctla4 has no correlation with surface immunosenescence markers. Based on the results of roc analysis, sCTLA-4 was the best predictor to determine immunosenescence with area under curve of 0.7. The cut-off value for sCTLA-4 to determine immunosenescence is 26.5 ng/ml with sensitivity and specificity 58.6% and 63.2% respectively. Conclusion: sCTLA-4 as a soluble costimulatory molecule can be developed as promising predictive biomarkers of immunosenescence, which could be detected more quickly and efficiently using elisa as an alternative to flowcytometry.
Impact of walking exercise intensity on cartilage IL-1, TNF-α, IL-4, MMP-13 and pain threshold in osteoarthritis rat models Handono, Kusworini; Prasetyo, Dwi A.; Kurnianingsih, Nia; Wahono, Cesarius S.; Albaar, Thoha M.
Narra J Vol. 5 No. 2 (2025): August 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i2.2109

Abstract

Pro-inflammatory cytokines produced by chondrocytes play a crucial role in activating matrix metalloproteinase-13 (MMP-13), leading to an imbalance between the synthesis and degradation of the extracellular matrix (ECM) in osteoarthritis (OA). Although regular walking exercise has been shown to reduce inflammatory cytokine levels in OA animal models, the optimal exercise intensity remains underexplored. Therefore, the aim of this study was to investigate the effects of different intensities of regular walking exercise on the levels of pro-inflammatory cytokines (interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α)), anti-inflammatory cytokine (interleukin-4 (IL-4)), as well as MMP-13 expression in cartilage and pain thresholds in an OA animal model. A total of 30 adult male Rattus norvegicus (6–8 weeks old) were divided into five groups: (1) healthy control; (2) monosodium iodoacetate (MIA)-induce OA model; (3) OA with light-intensity walking (OA1); (4) OA with moderate-intensity walking (OA2); (5) and OA with high-intensity walking (OA3). The exercise intervention began one week after MIA injection and continued for six weeks. Pain threshold, inflammatory cytokine (IL-1, TNF-α, IL-4) levels, and MMP-13 expression were measured using an analgesymeter, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC), respectively. The results demonstrated a significant reduction in IL-1 and TNF-α levels, along with decreased MMP-13 expression and increased IL-4 levels, in all exercise groups (OA1, OA2, OA3) compared to the untreated OA group. Additionally, pain thresholds improved following exercise. However, no significant differences were observed among the three exercise intensities in terms of cytokine levels, MMP-13 expression, or pain threshold. This study highlights that the light-intensity regular walking exercise effectively reduces inflammation, MMP-13 expression, and pain in OA. Further research is needed to elucidate the underlying mechanisms of exercise in OA management.
Coenzyme Q10 as adjuvant therapy could reduce oxidative stress and enhance sperm quality in cryptorchidism animal models Nurhadi, Pradana; Daryanto, Besut; Dhani, Fauzan K.; Purnomo, Athaya F.; Kusworini, Kusworini; Alfandy, Tommy N.
Narra J Vol. 5 No. 2 (2025): August 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i2.2474

Abstract

The role of coenzyme Q10 (CoQ10) as an antioxidant in the context of cryptorchidism is increasingly recognized due to its potential protective effects against oxidative stress, a key contributor to testicular dysfunction in this condition. The aim of this study was to evaluate the antioxidant activity of CoQ10 and its impact on sperm parameters as an adjuvant therapy in a cryptorchidism mouse model. A total of 36 male Sprague Dawley mice were divided into six groups: control (negative control), cryptorchidism (positive control), orchidopexy only, and orchidopexy treated with CoQ10 at 5, 10 and 20 mg/kg body weight (BW). After seven days of induction into the cryptorchidism model, the mice underwent orchidopexy, and CoQ10 was administered orally from day 1 to day 7 post-orchidopexy. At the end of the treatment period, all mice were euthanized, and the left testes were collected for immunohistochemical analysis of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as histological examination and sperm parameter assessment. Testicular tissue damage was assessed using the Cosentino grade, while spermatogenesis was evaluated using the Johnsen scoring system. Additionally, sperm parameters were analyzed from the left testis. MDA expression in the cryptorchidism group was significantly lower than in all CoQ10-treated groups (p<0.001). In contrast, SOD expression was significantly higher in the cryptorchidism group compared to the 10 mg/kg BW and 20 mg/kg BW CoQ10 groups (both had p<0.001). Cosentino grade and Johnsen score showed no significant differences between the control group and the group treated with 20 mg/kg BW CoQ10 (p=0.891 and p=0.123, respectively). Furthermore, the 20 mg/kg BW CoQ10 group had significantly greater sperm concentration and motility compared to the cryptorchidism group (p<0.001 for both). These findings demonstrated that CoQ10 had significant antioxidant activity as an adjuvant therapy in a cryptorchidism mouse model. CoQ10 supplementation could reduce oxidative stress markers, enhance antioxidant enzyme expression, and improve sperm parameters, supporting its potential to mitigate testicular damage associated with cryptorchidism.
A Synergistic Approach: Enhanced Apoptotic and Proliferative Inhibition of Cisplatin by Nanocurcumin in HeLa Cells Subandi, Subandi; Gizta, Aura Bella; Balindra, Fredlina Rossa; Handono, Kusworini; Khotimah, Husnul
Journal of Food and Pharmaceutical Sciences Vol 13, No 2 (2025): J.Food.Pharm.Sci
Publisher : Integrated Research and Testing Laboratory (LPPT) Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/jfps.21389

Abstract

Cisplatin is a widely used chemotherapeutic agent for cervical cancer, but its effectiveness is often limited by cellular resistance and severe side effects. Curcumin has demonstrated potential to enhance cisplatin's anticancer effects by inducing apoptosis and inhibiting cell proliferation; however, its clinical use is constrained by poor solubility and low bioavailability. To overcome these limitations, liposomal nanocurcumin was developed. This study aimed to evaluate the synergistic effects of cisplatin and nanocurcumin on Bax and BrdU expression as markers of apoptosis and proliferation in HeLa cervical cancer cells. A true experimental post-test only design was employed with five groups: HeLa cell control (no treatment), positive control (cisplatin 5 µg/mL), and three treatment groups receiving cisplatin 2.5 µg/mL combined with nanocurcumin at 25, 50, and 100 µg/mL. Cells were incubated for 48 hours and analyzedusing flow cytometry. The combination treatment significantly increased Bax expression and reduced BrdU expression compared to cisplatin alone, with the strongest effect observed at 100 µg/mL nanocurcumin. These findings suggest that nanocurcumin may serve as a promising adjuvant to enhance the therapeutic efficacy of cisplatin by promoting apoptosis and suppressing proliferation in cervical cancer cells.
Co-Authors Abd. Rasyid Syamsuri Abdurrachman Abdurrachman Achmad Rifa’i, Achmad Achmad Rudijanto Achmad Rudijanto Agustina T Endharti, Agustina T Agustina Tri E Agustina Tri Endharti Ahmad Bayhaqi Nasir Aslam Airlangga, Dimas Ikhsan Albaar, Thoha M. Alfandy, Tommy N. Asih, Sari Wulan Ati Rastini Atma Gunawan Atma Gunawan Atma Gunawan Aulanni'am, Aulanni'am Balindra, Fredlina Rossa Bambang Rahardjo Benny A Pradana, Benny A Bowo Hery Prasetyo, Bowo Hery BP Putra Suryana BP Putra Suryana Cesarius Singgih Wahono Dalhar, Mochamad Dantara, Tri W.I. Dany Farida Desfryda, Elynca Putri Dessy Setiawati desy wulandari Dewi Purnama Sari Dewi, Elvira S. Dhani, Fauzan K. Dhian E. P. Harnandari Dian Ayu Wulansari, Dian Ayu Dian Hasanah Dian Sukma Hanggara Dimas Ikhsan Airlangga Djoko W. Soeatmadji Dona Marisa, Dona Dwinadella, Sephia Eko, Mudjiwijono Handaru Elvira Sari Dewi Ema Pristi Yunita Ema Pristi Yunita, Ema Pristi Engli, Katherina Enny Listyawati Erawati, Dini Rachma Erna Amin Faisal Faisal Farida ** Fatchiyah Fatchiyah Firdaningrum, Nimas Eka Gizta, Aura Bella Handono Kalim Hani Susanti, Hani Hani Susianti Hanik Ruliani Haribowo, A S Hidayat Sujuti HMS Chandra Kusuma I Putu A.S Ibrahim Njoto Ihda Dian Kusuma Indah Jayani Ivan A Hartono, Ivan A Janasti, Laksmitha Krisni Subandiyah Kurnianingsih, Nia L Enggar Fitri Laksmi Karunia Tanuwijaya Laksmi Karunia Tanuwijaya Lisyani Suromo Loeki Enggar Fitri M Rasjad Indra Machlusil Husna, Machlusil Maghfirah, Halimi Bidaimi Marsetyawan HNE Soesatyo Muhammad Anshory, Muhammad Muhammad Masyhur Nelly Ismayasih Nurdiana Nurdiana Nurhadi, Pradana Perdana Aditya Rahman Poetri, Levrita Nindya Pramadhani, Almira Prasetyo, Dwi A. Pratama, Mirza Z. Pratama, Mirza Zaka Purnomo, Athaya F. Purwanto Adipireno Putri, Choirinnisa Meilia Ayu Putu A. Herliawati R.I R.I Radhitio A Nugroho, Radhitio A Rahmawati, Hanifa Rizky Ria Famuji, Siti Roziah Rifa’i, A Rizky Fachry, Ade Wlidan Rossy Meilani Rulli Rosandi Safrina Dewi Ratnaningrum, Safrina Dewi Sari, Riana Trinovita Sari, Tita Luthfia Satrio Wibowo Singgih Wahono Solly Aryza Sri Andarini Indreswari Sri Poeranto, Sri Subandi Subandi Suharyo Hadisaputro Sulistomo, Hikmawan Wahyu Sulistyorini Sulistyorini Sumarno . Sumarta, Norma Hanifah Suryana, Bagus Putu Putra Sutrisno Sutrisno Suwito, Mat Syahrul Chilmi Tatit Nurseta Tatit Nurseta Torajasa Achamar Tri Yudani Mardining Raras VALENTINA YURINA VALENTINA YURINA Wahono, Caesarius Singgih Wahono, Cesarius S. Wahono, Cesarius Singgih Wisnu Barlianto Wisnu Barlianto Wisnu Barlianto Yahya Irwanto Yona One Sidarta, Yona One Yudhanto, Hendy Setyo Yuliana Salman Zaenal Kusuma