DSpace Community:

Penilaian peranan neuroprotektif metalotionin dalam model penyakit parkinson aruhan rotenone pada danio rerio: kajian in vivo

Tue, 19 May 2026 00:00:00 GMT

Title: Penilaian peranan neuroprotektif metalotionin dalam model penyakit parkinson aruhan rotenone pada danio rerio: kajian in vivo Authors: Nies Yong Hui Abstract: Penyakit Parkinson (PD) ialah gangguan neurodegeneratif progresif yang dikaitkan dengan degenerasi neuron dopaminergik (DA) secara selektif dalam substantia nigra pars compacta akibat tekanan oksidatif, disfungsi mitokondria, dan disregulasi imun. Kajian ini bertujuan untuk menyiasat kesan rawatan Metalotionin-2 manusia (hMT2) dalam model PD zebrafish (Danio rerio) yang dicetuskan oleh rotenone. Sejumlah 228 ekor zebrafish dewasa telah dibahagikan kepada empat kumpulan eksperimen: kawalan (n=58), rotenone (n = 60), prarawatan hMT2 (n=55), dan pascarawatan hMT2 (n = 55). Zebrafish didedahkan kepada rotenone pada kepekatan 5 μg/L di dalam air selama 28 hari untuk mencetuskan fenotip PD. Protein hMT2 eksogen (0.2 μg/ikan) kemudiannya disuntik secara intrakranium ke dalam zebrafish satu hari sebelum pendedahan kepada rotenone bagi intervensi profilaksis (prarawatan hMT2) dan 28 hari selepas pendedahan kepada rotenone bagi intervensi terapeutik (pascarawatan hMT2). Parameter analisis yang dinilai secara holistik termasuklah analisis aktiviti lokomotor, analisis biokimia bagi tekanan oksidatif (TBARS), penilaian respirasi mitokondria menggunakan MitoPlate I-1, pewamaan imunohisto-kimia pada neuron DA, serta analisis mikrosusunan yang disahkan melalui qPCR. Hasil kajian menunjukkan bahawa pendedahan kepada rotenone berjaya memanifestasikan ciri-ciri patologi klinikal PD melalui penurunan aktiviti lokomotor (p<0.05), peningkatan fenotip keresahan (p< 0.001), dan ketahanan terhadap perencat kompleks II rantai pengangkutan elektron (ETC) serta meklizin mitokondria yang membawa kepada peningkatan dalam tekanan oksidatif (TBARS, p<0.001). Pada peringkat sel, neurotoksisiti rotenone mengganggu homeostasis DA (dat, th1, th2; p<0.001), mengurangkan sokongan neurotropik (bdnf. p<0.001), dan mencetuskan neuroinflamasi progresif melalui pencetusan sitokin pro- keradangan (il-la, il-lb. cox-2, tnf-a;p<0.001), mikrogliosis reaktif (tyrobp; p< 0.001), dan pengaktifan agresif sistem imun adaptif yang dikawal perantara oleh sel T sitotoksik CD8 (gzm3, cd8a, themis, Ick, p < 0.001). Kerosakan neuron ini dikawal perantara oleh peningkatan regulasi gen pro-apoptosis (deddl; p < 0.001) yang mencetuskan pelaksanaan apoptosis melalui laluan ekstrinsik. Walau bagaimanapun, intervensi menggunakan hMT2 telah terbukti menunjukkan neuroprotektor multisasaran yang berkesan. hMT2 berjaya menstabilkan semula aktiviti lokomotor, melemahkan mikropersekitaran CNS yang meradang melalui penindasan lata sitokin, menyekat pengaktifan mikroglia (tyrobp;p<0.001), dan menormalkan pengekspresan gen pengaktifan sel T patogenik (gzm3, cd8a, themis, lck, p<0.05). Dapatan paling berimpak menyimpulkan bahawa kecekapan hMT2 adalah dinamik dan bersandarkan masa. Pendekatan profilaksis didapati unggul dalam perlindungan struktur sel hulu melalui pemeliharaan populasi neuron DA (p < 0.05), penstabilan mitokondria (p < 0.001), dan rintangan terhadap fasa pelaksanaan apoptosis melalui penindasan genetik bagi gen deddl (p<0.05). Sebaliknya, pendekatan terapeutik menunjukkan keunggulan dalam pemulihan berfungsi hilir dengan menyediakan pengurangan maksimum bagi beban tekanan oksidatif sistemik (TBARS; p<0.001), meringankan keradangan akut (il-la, il-lb, cox-2, tnf-a; p < 0.001), dan mengaktifkan gen pertahanan endogenus zebrafish (mt2 dan smtb; p<0.001) untuk pemulihan motor yang lebih cekap. Secara keseluruhan, data daripada kajian ini menyediakan asas praklinikal yang kukuh untuk mencadangkan hMT2 sebagai modaliti rawatan dwifungsi (profilaksis dan terapeutik) yang berpotensi dalam menghentikan atau memperlahan perkembangan neurodegenerasi untuk pengurusan PD pada masa hadapan.

Estimating the value of statistical life and evaluating quality of life outcomes among motorcycle crash survivors at selected public health providers

Mon, 25 May 2026 00:00:00 GMT

Title: Estimating the value of statistical life and evaluating quality of life outcomes among motorcycle crash survivors at selected public health providers Authors: Shamsinar Ibrahim Abstract: Road Traffic Injuries (RTIs) remain a pressing public health concern, particularly in assessing survivors' Quality of Life (QoL) and economic valuations. This cross- sectional study estimated the Value of Statistical Life (VOSL) through Willingness to Pay (WTP) per year for reductions in fatality and injury risk, national road safety programs, and medical treatment (initial and follow-up) among motorcycle crash survivors. It also evaluated QoL one month post-discharge. Data were collected between August 2022 and September 2023 at the emergency departments of Hospital Sultanah Bahiyah (Alor Setar) and Hospital Sungai Buloh (Selangor). The Contingent Valuation Method (CVM) estimated VOSL from WTP, while the Revised Trauma Quality of Life (RT-QoL) instrument assessed QoL. Descriptive statistics, Generalized Linear Models (GLM) with Gamma distribution, and Binary Logistic Regression (BLR) were used. Of 546 respondents, 81% were pillion riders and 364 were male. Mean WTP per year was RM28 for fatality risk reduction, RM53 for injury risk, RM36 for safety programs, RM64 for emergency eare, and RM59 for follow-up treatment, estimating fatality costs at RM94,058 - RM101,294 and injury at RM24,495 - RM28,850. WTP for national safety programs was valued at RM725,333 - RM768,000. WTP for fatality risk reduction was influenced by education, income, insurance, and travel purpose; injury risk WTP by age, education, occupation, insurance, travel purpose, and crash history; and WTP for safety programs by similar factors as injury risk. Emergency treatment WTP was higher among younger individuals, those with higher education, mid-skilled workers, and lower among B40 groups, reflecting healthcare access disparities. Follow-up WTP was shaped by occupation, income, injury type, insurance, license status, and travel purpose. QoL outcomes were predicted by education, ethnicity, and occupation across emotional, functional, and physical domains. Emotional QoL was reduced by low income, lack of license or insurance, and fractures, with fractures associated with 38.3% lower odds of high emotional well-being. Functional QoL was linked to injury severity (MAIS), license status, pillion riding, insurance, and crash history. Physical QoL was associated with income, household size, insurance, travel purpose, and rider type, with pillion riders reporting better outcomes. Overall, the study emphasizes the role of socio-demographic and pre-crash factors in shaping both WTP and QoL, highlighting the need for targeted policies, equitable healthcare, and educational interventions for vulnerable road users.

Pengaruh mineral lempung terhadap potensi hakisan tanah bercerun berdasarkan mekanisme penyerakan dan pengasingan

Tue, 18 Feb 2025 00:00:00 GMT

Title: Pengaruh mineral lempung terhadap potensi hakisan tanah bercerun berdasarkan mekanisme penyerakan dan pengasingan Authors: Azlan Shah Nerwan Shah @ Nintin (P110363) Abstract: Mineral lempung merupakan bahan mudah terhakis yang wujud sebagai sebahagian komponen tanah baki dengan litologi batuan yang berbeza. Serakan dan pengasingan merupakan mekanisme hakisan utama apabila mineral lempung berinteraksi dengan air. Kemampuan tanah untuk terhakis secara permukaan dan dalaman berpotensi untuk menyumbang kepada kejadian tanah runtuh. Objektif kajian ini dijalankan untuk mencirikan sifat fiziko-kimia tanah baki, menentukan kebolehupayaan serakan tanah berdasarkan jenis mineral lempung, mengukur morfometrik rekahan dan menentukan kadar pengasingan bagi melihat kebolehupayaan tanah untuk terhakis di bawah pengaruh penyerakan dan daya aliran air. Pengukuran kadar pengasingan tanah dijalankan melalui simulasi flum menggunakan sampel tanah kering manakala ujian penyerakan lubang pin menggunakan sampel tanah lembab. Kawasan persampelan tanah baki melibatkan beberapa kawasan cerun di negeri Sabah, Selangor, Kedah dan Negeri Sembilan dengan berpandukan kepada tiga jenis batuan induk yang berbeza (igneus, metamorf, sedimen). Berdasarkan analisis sifat indeks, tanah baki sedimen merekodkan kandungan lempung (Lg) yang lebih tinggi dengan julat 3.08–43.70% berbanding tanah baki igneus (1.49–5.08%) dan metamorf (0.26–9.30%). Tanah baki sedimen mempunyai kewujudan mineral dominan seperti kuarza di samping variasi mineral lempung seperti kaolinit, ilit, montmorilonit dan vermikulit yang mempengaruhi kapasiti pengembangan-pengecutan tanah. Analisis tahap serakan menunjukkan mineral lempung montmorilonit lebih cenderung untuk terserak diikuti ilit, kaolinit dan vermikulit. Analisis morfometrik rekahan tanah menunjukkan tanah terserak merekodkan nilai faktor intensiti rekahan (CIF) dan faktor ketumpatan rekahan (CDF) yang lebih tinggi berbanding tanah tidak terserak dengan masing-masing berjulat 16.70–28.20% dan 27.99–38.90%. Nilai pengasingan tanah terserak yang ditentukan daripada simulasi flum adalah lebih rendah dengan julat 0.000174–0.000328 kg/m2/s berbanding nilai pengasingan daripada ujian penyerakan lubang pin dengan julat 0.01252–0.02055 kg/m2/s. Analisis komponen prinsipal (PCA) menjelaskan hakisan dalaman adalah dipengaruhi oleh faktor serakan tanah manakala hakisan permukaan lebih dipengaruhi oleh daya dan kuasa aliran air. Pemerhatian menunjukkan tindakan aliran air di permukaan tanah menyebabkan hakisan mengufuk lebih dominan berbanding hakisan menegak akibat pembebasan tekanan ke atas permukaan yang luas. Sebaliknya, penumpuan aliran air di dalam ruang terkekang (confined) di dalam tanah menyebabkan penumpukan tenaga di kawasan yang lebih kecil sekaligus menyebabkan hakisan menegak lebih dominan berbanding hakisan mengufuk. Keadaan ini menyumbang kepada pembukaan rongga tanah secara paip dan mengurangkan ketumpatan tanah lalu membentuk zon lemah di dalam tanah. Secara keseluruhannya, kadar pengasingan minimum tanah untuk terhakis secara dalaman adalah 66 kali ganda lebih tinggi berbanding hakisan permukaan. Keadaan ini membuktikan kapasiti ketahanan tanah terhadap hakisan adalah sangat rendah di sub-permukaan berbanding permukaan walaupun tindakan air lebih dominan di permukaan. Dominasi hakisan dalaman berbanding permukaan juga menyebabkan kaviti tanah meningkat secara agresif di bawah pengaruh serakan dan berpotensi membentuk zon lemah yang mampu mengganggu struktur tanah. Penemuan ini juga menunjukkan faktor hakisan dalaman tanah perlu diberi perhatian dalam menilai kestabilan cerun tanah terserak bagi mengawal risiko pembentukan satah gelinciran yang berpotensi menyebabkan kejadian tanah runtuh.

Formation of human bone via tissue engineering technique with the addition of growth factors and telomerase gene transfection

Mon, 07 Jul 2008 00:00:00 GMT

Title: Formation of human bone via tissue engineering technique with the addition of growth factors and telomerase gene transfection Authors: Ng Min Hwei Abstract: Tissue engineering aims to create an autologous or universal tissue or organ in order to restore and enhance biological function by combining the principles of engineering and life sciences. This study is an endeavour to devise a strategy for human bone tissue engineering that encompasses the process of sample harvesting, cell expansion, three-dimensional construct formation in vitro and the implantation of the autologous engineered bone construct to repair critical-sized bone defect in an animal model. There were five distinct phases in the study. In Phase I, four cell sources: periosteum, cancellous bone, cortical bone and bone marrow aspirate were harvested and expanded in culture. The four cell sources exhibited osteogenic differentiation capabilities and hence can be pooled for generating three-dimensional bone construct. Periosteum proved to be superior in terms of growth profile and the degree of osteogenic advancement. However, bone marrow mesenchymal stem cells (BMSCs), a potential candidate for future clinical applications had been further characterized for surface markers (CD markers) and telomerase activity. Due to the decreased proliferation capacity and telomerase activity in BMSCs of aged individuals, it was hypothesized that the ectopic expression of human telomerase reverse transcriptase (hTERT), the key component of telomerase activity, in BMSCs will increase cellular proliferation and life span. The effect of BMSC transfection with hTERT gene was hence being studied. Phase II of the study then explored the use of growth factors to expedite the proliferation and differentiation of BMSCs in vitro. The effect of transforming growth factor-beta 1 (TGF-B1), insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (bFGF) and bone morphogenetic protein 2 (BMP-2) in different dosages on the monolayer cultures were evaluated. bFGF addition effected a significant increase in BMSCs proliferation in parallel with increasing dosage. Phase III embarked on the formation of three-dimensional bone constructs. Ceramic hydroxyapatite (HA) and a composite of tricalcium phosphate and hydroxyapatite (TCP/HA) were selected for use as the scaffolding material. Continuous seeding is the method of choice for cell seeding when compared to static seeding and human plasma derivative, upon polymerization, acted as a cell carrier and growth factor delivery. In Phase IV, the two ceramic materials; HA and TCP/HA were compared in parallel. Evaluations of in vitro and in vivo constructs supported the hypothesis that TCP/HA, due to its higher biodegradability accelerated new bone formation and is the preferred scaffold material for bone tissue engineering. Finally, for proof of concept, one- centimeter tubular bone was removed from the right tibia of 21 three-month old New Zealand White Rabbits and was replaced with autologous tissue engineered bone constructs, allografts, fresh bone marrow loaded scaffolds or were left blank as controls. New bone developed in the tissue engineered bone constructs, which fused onto adjacent native bone. Greater biomechanical strength and physiological function were achieved in tissue engineered bones when compared to other approaches. In conclusion, we have proved that bone repair using the tissue engineering approach is feasible.