139 research outputs found

    The challenges of using Escherichia coli as a host in recombinant insulin production

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    Diabetes mellitus is a metabolic disease characterised by elevation of blood glucose level which leads to serious damage to the blood vessels, eyes, heart, kidney, and nerves affecting about 830 million people worldwide. The most common diabetes is type 2 which usually happened in adults when the body becomes resistant to insulin, or the body does not produce enough insulin. Type 1 diabetes mellitus is dependent on insulin which required accessible and affordable insulin (Diabetes, 2025). In Malaysia, the prevalence of diabetes mellitus (DM), depends on factors such as gender, age, and ethnicity, with women, the elderly, and the Indian community having the highest prevalence of DM. In the 103,063 participants that made up the study's sample, the combined prevalence of diabetes by gender in the population-based studies was 13.80% for men and 14.54% for women, while the combined prevalence of prediabetes was 11.40% for women and 10.98% for men (Akhtar et al., 2022). For age, from this study, it can be observed that the prevalence of diabetes showed a notable upward trend as people aged, rising from 3.16% in the 20–29 age group to 13.71% in the 30-45 age group, 25.66% in the 46–59 age group, and 33.45% in the 60 and older age group (Akhtar et al., 2022). Ethnicity and races can also affect the prevalence of DM. The subpopulation of Indian had the greatest prevalence of diabetes which is 25.10%, among all ethnic groups, followed by Malay with 15.25%, Chinese with 12.87%, Bumiputera with 8.62%, and others with 6.91%. The prevalence demands oral hypoglycaemic agents (OHAs) market size in Malaysia at USD282.22 million in 2025 with a CAGR of greater than 3% during forecast period (2025-2030). The drugs are mainly fall under the following segment: biguanides, alpha-glucosidase inhibitors, dopamine-d2 receptor agonists, sodium-glucose cotransport-2 (SGLT-2) inhibitor, dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas, and meglitinides (Malaysia Oral Anti-Diabetic Drug Market Size | Mordor Intelligence, 2025)

    The Validation of the Exegetical Views of al-Mizan and al-Manar about “Raising the Mountains” and “Metamorphosis of Bani Isra’il”

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    Despite the different and sometimes contradictory perceptions and interpretations of the Noble Qur’an within the past 14 centuries, the unprecedented developments in the realm of empirical science at the contemporary age have made the commentators to boost their scientific and rational look at the Qur’anic verses regardless of their different exegetical methods and principles. Muhammad Abduh as one of the founding figures of Neo-Mu’tazilism has attempted to adopt a moderate approach to the extraordinary events in the Qur’an. Therefore, although he has admitted those events he has also proposed some scientific probabilities and justifications for them. However, the author of Tafsir al-Mizan holds that bringing scientific justifications denotes the denial of the extraordinary events in the Qur’an. Allameh Tabatabaii believes that the appropriate perception is to accept the miracles as extraordinary events beyond scientific rules. He has also focused on the philosophical and rational interpretation of those extraordinary events that seems to be more logical in his view. The subject of the present study is the comparative study of “raising the mountain” and “metamorphosis of Bani Isra’il” as two extraordinary events in the Qur’an and the validation of the evidences for them. © Razawi, S.M; Taher, M; Nabavi, S.M. (2020) The Validation of the Exegetical Views of al-Mizan and al-Manar about “Raising the Mountains” and “Metamorphosis of Bani Isra’il”. Biannual Journal of Comparative Exegetical Researches, 6 (11) 207-234.  Doi: 10.22091/ptt.2020.4428.157

    In vitro antioxidant, cholinesterase and tyrosinase inhibitory activities of calophyllum symingtonianum and calophyllum depressinervosum (guttiferae)

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    Objective: To screen the antioxidant, cholinesterase and tyrosinase enzymatic inhibition activities of the leaves and heartwood of Calophyllum symingtonianum (C. symingtonianum), and the bark of Calophyllum depressinervosum (C. depressinervosum). Methods: Samples of leaves and heartwood of C. symingtonianum and bark of C. depressinervosum were tested for their total phenolic content and in vitro antioxidant assay by 2,2-diphenyl-1-picrylhydrazyl radical scavenging and β-carotene bleaching. Cholinesterase inhibition by Ellman’s method and tyrosinase inhibition using L-3,4-dihydroxyphenylalanine as a substrate were also tested. Results: All methanol extracts were found to exhibit strong 2,2-diphenyl-1-picrylhydrazyl radical scavenging effects. Extracts from the heartwood of C. symingtonianum gave a low IC50 (5.17±0.04) µg/mL followed by bark of C. depressinervosum [(7.30±0.14) µg/mL] and C. symingtonianum leaves [(15.70±1.43) µg/mL]. The methanol extract of C. depressinervosum bark showed 95.08% inhibition of β-carotene bleaching. All extracts showed moderate inhibition towards tyrosinase activity with an IC50 of more than 100 µg/mL. The methanol extract of C. depressinervosum stem bark showed the highest inhibition (78.46%) against butyrylcholinesterase. Conclusions: These results showed that both Calophyllum species are potential sources of antioxidant and cholinesterase inhibitors. Further study is needed for the isolation and characterization of the active metabolites responsible for both activities

    Antimicrobial, antioxidant, anti-inflammatory and cytotoxic activities of Garcinia Eugenifolia and Calophyllum Enervosum

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    Chemical investigation of Garcinia eugenifolia and Calophyllum enervosum yielded six compounds. One of these was found to be a novel compound identified as enervosanone. Five known compounds cambogin, epicatechin, osajaxanthone, rubraxanthone and isocowanol, were also isolated. These compounds were tested for their bioactivity as antimicrobial, antioxidant and cytotoxicagents. Antimicrobial assay was performed using disc diffusion method. The antioxidative activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method by electron spin resonance. The cytotoxicity was measured by the MTT assay against MCF7 cell line. Enervosanone and rubraxanthone were active against Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus with MIC value of 26.82, 26.82, 26.82, 26.82 and 60.97, 30.48, 60.97, 60.97 mM, respectively. Rubraxanthone and epicatechin exhibited antioxidant activities with IC50 of 0.89 mM and 2.6 mM, respectively. The cytotoxicity assay on MCF7 cell line showed that enervosanone was found to be active in inhibiting cell proliferation of MCF7 with IC50 of 1.07 mM

    The role of podoplanin inhibitors in controlling oral cancer progression

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    Objective: In this article, we review the current studies on the role of podoplanin in oral cancer and the potential application of podoplanin inhibitors as a therapeutic agent for oral cancer. Design: The narrative review approach was conducted, providing a comprehensive perspective of related literature. Publications addressing podoplanin and its inhibitors in the context of oral cancer were retrieved from PubMed and Scopus databases. Results: Podoplanin has emerged as a biomarker and therapeutic agent for oral cancer. Numerous studies have reported high podoplanin expression in oral cancer and pre-cancerous lesions compared to normal cells. A specific inhibitor targeting podoplanin may have the potential to prevent oral carcinogenesis via interfering with the pathway of cancerous cells involved in cell proliferation and metastasis. Antibodies, chimeric antigen receptor (CAR)-T cells, cancer-specific mAb (CasMab), synthetic molecules, and lectins are among the materials used as anticancer agents targeting podoplanin. Plant-derived lectins appear to demonstrate a unique advantage against alternative candidates. Conclusions: The use of podoplanin inhibitors in place of existing therapeutic approaches could be a promising and novel approach to the prevention and treatment of oral cancer. Nevertheless, further research is required to investigate the practical application of such inhibitors

    Cellular mechanosensitivity in vitro: cell-ECM, cell-cell, and cell-material interactions

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    Made available in DSpace on 2015-09-29T21:02:41Z (GMT). No. of bitstreams: 2 ALI-DISSERTATION-2015.pdf: 4946984 bytes, checksum: 649de0269d74763792c883cf2346193d (MD5) LICENSE.txt: 4215 bytes, checksum: b416febe9eaf70ac46d72a4e366da385 (MD5) Previous issue date: 2015-05-13Embargo set by: Seth Robbins for item 89520 Lift date: 2017-09-29T21:03:28Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 89520 Lift date: 2017-09-29T21:08:35Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 89520 on 2017-09-30T09:15:30Z.In recent years it has become increasingly evident that physical cues like mechanical micro-environment and geometry, in addition to bio-chemical factors, plays an important role in regulating cell functionalities. Cancer cells also respond to 2D and 3D matrix stiffness in a complex manner using a coordinated, hierarchical mechano-chemical system composed of adhesion receptors and associated signal transduction membrane proteins, the cytoskeletal architecture, and molecular motors. Mechanosensitivity of different cancer cells in vitro are investigated primarily with immortalized human cancer cell lines or murine derived primary cells, not with primary human cancer cells. Hence, little is known about the mechanosensitivity of primary human colon cancer cells in vitro. In the first part of this dissertation, an optimized protocol is described that demonstrates the isolation of primary human colon cells from healthy and cancerous surgical human tissue samples. Isolated colon cells are then successfully cultured on soft (2 kPa stiffness) and stiff (10 kPa stiffness) polyacrylamide (PA) hydrogels and rigid polystyrene (~3.6 GPa stiffness) substrates functionalized by an extracellular matrix (fibronectin in this case). Fluorescent microbeads are embedded in soft gels near the cell culture surface, and traction assay is performed to assess cellular contractile stresses. Our findings suggest that both the healthy and tumor cells are mechanosensitive. Their average spread area increased with increase in substrate stiffness, and they displayed actin stress fibers and elongated focal adhesions on rigid polystyrene substrates only. Traction cytometry results on soft gels are the first experimental evidence that primary colon tumor cells can generate augmented traction compared to their healthy counterparts. In addition, the contrast between traction patterns and metastatic staging raises the possibility of introducing a potent biophysical marker of cancer metastasis with other molecular biomarkers. In the second part, we study the role of cell-cell adhesions on the substrate elasticity mediated metastasis-like phenotype (MLP) of human colon carcinoma (HCT-8) cells. HCT-8 cells on PA gels is an attractive in vitro biomaterial platform as they exhibit a dissociative, metastasis-like phenotype (MLP) when cultured on extra-cellular matrix (ECM) coated gels with appropriate mechanical stiffness (20–47 kPa), but not on very stiff (3.6 GPa) polystyrene substrates. We ask the question whether similar morphological transition occurs on cell-cell adhesion molecule, i.e., E-cadherin coated PA gels and if so, how the actin cytoskeleton and focal adhesions compare with ECM mediated response on gels. Experimental results suggest that MLP of HCT-8 cells on PA gels is independent of cell to gel adhesion in 2D in vitro culture. Finally, we challenge the classical readouts of cellular mechanosensing by examining cell response on soft biological gel, namely, collagen. Our results show that different types of fibroblasts can exhibit spread morphology, well defined actin stress fibers, and larger focal adhesions even on very soft collagen gels (modulus in hundreds of Pascals) as if they are on hard glass substrate (modulus in GPa, several orders of magnitude higher). Strikingly, we show, for the first time, that augmented cell spreading and other hard substrate cytoskeleton architecture on soft collagen gels are not correlated with cell proliferation pattern unlike PA gels and do not require nuclear transcriptional regulator YAP (Yes associated protein) localization in cell nucleus. HCT-8 cell clusters also show augmented spreading/wetting on soft collagen gels unlike PA gels and eventually form confluent monolayer as on rigid glass substrates and MLP is completely inhibited on soft collagen gels. Overall, these results in the third part suggest that cell-material interaction (soft collagen gels in this case) can induce cellular phenotype and cytoskeleton organization in a remarkably distinct manner compared to a classical synthetic polyacrylamide (PA) hydrogel cell culture model and may contribute in designing new functional biomaterials.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2017-08-01The student, Muhammad Yakut Ali, accepted the attached license on 2015-05-06 at 19:14.The student, Muhammad Yakut Ali, submitted this Dissertation for approval on 2015-05-06 at 19:15.This Dissertation was approved for publication on 2015-05-13 at 13:58.DSpace SAF Submission Ingestion Package generated from Vireo submission #8214 on 2015-09-29 at 15:04:5

    Antimicrobial and cytotoxicity activities of sterculia parviflora

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    In this modern world, plants and natural resources are being so significant in various pharmacological and drug research. The search for new antimicrobial and anticancer remedies is among the most prominent research fields nowadays. The aims of the present study are to evaluate the antimicrobial and cytotoxic activity of Sterculiaparviflora against the selected microorganisms and breast cancer cell line (MCF-7) respectively. S. parviflora’s leaves were extracted with n-hexane, ethyl acetate and methanol by using Soxhlet apparatus. At first, the extracts were analyzed for their phytochemical constituents such as alkaloids, flavonoids, saponins, steroids, terpenoids and phenolic. In the antimicrobial screening, the crude extracts were evaluated through disc diffusion and micro dilution methods against two Gram-positive bacteria (S. aureus and B. cereus), two Gram-negative bacteria (P. aeruginosa and E. coli) and two fungi (C. albicanand Aspergillus spp.). In disc diffusion method, the methanol extract exhibited antimicrobial potency against S. aureus and B. cereus which ranged within 8 to 10.7 mm of inhibition zone while ethyl acetate only inhibited B. cereus ranged within 14.7 to 26.3 mm. The Minimum Inhibitory Concentration (MIC) values of methanol extract against both S. aureus and B. cereus is 25 mg/mL while 50 mg/mL against B. cereus for ethyl acetate. The Minimum Bactericidal Concentration (MBC) values which indicated completely inhibition without visible growth of bacteria is at concentration of 50 mg/mL for methanol extract against both S. aureus and B. cereus while 100 mg/mL for ethyl acetate extract against B. cereus. In cytotoxicity study, MTT assay and tryphan blue exclusion methods were done to assess the percentage of viable cells of MCF-7 cell line after being treated with S. parviflora extracts. The results showed that all extracts did not exhibit significant cytotoxic effect on MCF-7 cancer cell line at concentrations of 100, 50, 25, 12.5, 6.25 and 3.125 mg/mL after 24 hours incubation. Moreover, the IC50 values of each extracts also would not be determined due to inability of extracts to reduce the viable cells percentage to be lower than 50%. In conclusion, the S. parviflora extracts exhibited potential antimicrobial activity against S. aureus and B. cereus while possessed no cytotoxic potency against MCF-7 breast cancer cell line

    The antimalarial properties of essential oils of the leaves of Malaysian Plectranthus amboinicus (Lour) spreng in mice infected with Plasmodium berghei

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    This study was conducted to evaluate the phytochemical contents and antimalarial properties of the oils extracted from the leaves of Malaysian Plectranthus amboinicus in mice infected with Plasmodium berghei. The essential oils were extracted and prepared by using steam distillation technique and subjected to phytochemical screening by using GC-MS. Antimalarial activity of different extract doses of the essential oil was tested in vivo in ICR mice infected with Plasmodium berghei (PZZ1/100) during early, established and residual infections. In all, 5 compounds made up 88.34% of total oil and the major chemical compounds were carvacrol (85.14%), thymoquinone (1.65%), terpinen-4-ol (0.70%), octenol (0.62%) and thymol (0.23%). Antimalarial assay showed this essential oil as a potential prophylactic agent with the percentage chemosuppression of 45.23%, 18.28%, 45.38% and 58.26% while treated with 50, 200, 400 and 1000 μL/kg respectively of essential oil and curative agent with percentage of chemo suppression of 54.10%, 47.35%, 56.75% and 65.38% while treated with the above dose of essential oil. Statistically no reduction of parasitemia was calculated for suppressive test. The extract has prophylactic and curative effects on P.berghei in mice

    The antihyperglycaemic and antiobesity effects of selected compounds from garcinia malaccensis on 3t3-l1 adipocytes

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    The increase incidence in diabetes-and obesity-related diseases in developed and developing countries has driven serious efforts towards the discovery of adipogenic differentiation-inhibitory compounds in natural products. Mangostins and triterpenoids from Garcinia have been reported to contain a wide range of bioactivities. However, its antidiabetic and antiobesity activity has not been previously addressed. With regard to the fact, this research is designed to study the antihperglycaemic and antiobesity effects of selected phytochemicals isolated from Garcinia malaccensis namely beta-mangostin and cycloartane triterpenoid. The compounds were tested for their antihyperglycaemic and antiobesity effects in 3T3-L1 adipocytes. In this study, we first elucidated the effects the compounds on the lipid accumulation of 3T3-L1 preadipocytes by using Oil Red O staining. The ability of the cell to uptake glucose was measured by liquid scintillation counter. Peroxisome proliferator-activated receptors gamma (PPARy), glucose transporter four (GLUT4) and leptin genes expression was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The results showed that β-mangostin reduced the triglyceride accumulation in 3T3-L1 adipocytes with highest lipid inhibition activity was observed at 50 μM concentration (p<0.05) when compared to MDI (0.5 mM 3-isobutyl-1-methyl-xanthine (IBMX), 0.25 mM dexamethasone, 1 μg/mL insulin) treated cells. On the other hand, treatment with cycloartane triterpenoid significantly induced lipid accumulation. Analyses of 2-deoxy-D-[3H] glucose uptake activities showed that all the compounds including the MDI, metformin and sodium orthovanadate (positive control) significantly (p<0.05) improved the glucose uptake when compared to the basal cell. In addition, evaluation by using the adipolysis kit (Cayman Chemicals) showed that β-mangostin increases the amount of free fatty acid (FFA) release. Further evaluation by the gene expression analysis showed that β-mangostin may reduce lipid accumulation by inhibition of the expression of PPARγ genes. In addition, induction of glucose uptake and free fatty acid release by β-mangostin was accompanied by increasing of mRNA expression of GLUT4 and leptin. Interestingly, mature 3T3-L1 cells treated with cycloartane triterpenoid was shown to enhance PPARγ and GLUT4 gene expression and decreased leptin expression. As a conclusion, these line of evidences indicated that β-mangostin and cycloartane triterpenoid derived from Garcinia malaccensis may become an interesting candidate for the prevention of metabolic disorders such as diabetes and obesity
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