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Frequency, geographical distribution, clinical characteristics, antivenom utilisation and outcomes of King Cobra (Ophiophagus hannah) bites in Malaysia

Renault A, Ng VERF, Goh WC, Hamid MNHA, Osman AMZ, Safferi RS, et al.

PLoS Negl Trop Dis, 2024 Jul 25;18(7):e0012359.
PMID: 39052675 DOI: 10.1371/journal.pntd.0012359

Snakebite envenomation remains an important, yet a neglected public health issue in most tropical and subtropical countries. Underdeveloped medical infrastructure, suboptimal medical services, poor documentation and failure to make snake-related injury a mandatory notifiable disease are important contributing factors. The King Cobra (Ophiophagus hannah) is a medically significant species encountered in Malaysia however, there have been few publications from the clinical perspective. The objectives of this study were to determine the frequency of King Cobra related injuries, geographical distribution, clinical presentation, type and frequency of antivenom utilization and the management outcome. This is a cross-sectional study of confirmed King Cobra related injuries consulted to Remote Envenomation Consultation Services (RECS) from 2015 to 2020. Data were extracted from the RECS database and descriptively analyzed. A total of 32 cases of King Cobra bite were identified. Most cases were from Peninsular Malaysia with the most frequent from the state of Pahang (n = 9, 28.1%). Most patients got bitten while attempting to catch or play with the snake (68.8%). Signs and symptoms of envenomation were documented in 24 (75.0%) cases and the most frequent systemic manifestation was ptosis (n = 13, 40.6%). Tracheal intubation and ventilatory support were required in 13 (40.6%) patients. Antivenom was administered to 22 (68.8%) patients with most (25.0%) receiving 10 vials (1 dose). The commonest antivenom used was monospecific King Cobra antivenom (50.0%) from Thai Red Cross. There was one death documented due to complications from necrotizing fasciitis and septicemia. Public awareness of the dangers and proper handling of King Cobras needs to be emphasised. Timely administration of the appropriate antivenom is the definitive treatment and leads to favorable outcomes.
Fulltext Protocol for a three-phase prospective study to develop educational resource of antimicrobial resistance and stewardship for medical programme

Dhaliwal JS, Mohamad Yusra MAM, Muharram SH, Akkawi ME, Hussain Z, Rahman H, et al.

BMJ Open, 2022 Feb 28;12(2):e049867.
PMID: 35228275 DOI: 10.1136/bmjopen-2021-049867

INTRODUCTION: Antimicrobial resistance (AMR) is one of the critical medical issues of the 21st century. Medical professionals are the primary prescribers of antimicrobials; their undergraduate education of antimicrobial stewardship (AMS) is considered one of the fundamental approaches in combating the issue of AMR. This education level provides a platform to bridge any gaps in their knowledge and competency in AMS. This study aims to develop an educational resource on microbes, hygiene and prudent antimicrobial use for the undergraduate medical programme. The guideline produced will then be assimilated into the existing curriculum which will help to improve the quality of education which in turn will improve rationale as the use of antimicrobials in the future.
METHODS AND ANALYSIS: A three-step approach consensus approach will be adopted for this study for the development of a validated medical curriculum guideline on AMR. A preliminary curriculum for the programme will be drafted from reviews of published literature including syllabi as well as national and international guidelines. A total of 26 potential sources were found to be relevant, and selected for this study. Subsequently, the drafted curriculum will be subjected for validation via online surveys by various infectious disease experts. Finally, a Delphi technique will be employed to obtain consensus on heterogeneous findings to the revised curriculum. The quantitative and qualitative responses will be analysed and discussed among the panel of researchers.
ETHICS AND DISSEMINATION: This study protocol has been approved by the Institute of Health Sciences Research Ethics Committee of Universiti Brunei Darussalam (Reference: UBD/PAPRSBIHSREC/2020/124). Informed consent declaration will be collected prior to data collections as indication of agreement of participation in the study. Results will be made available to medical educators and also researchers on AMR and stewardship. The results also will be disseminated at feedback sessions to officers at Ministry of Health and Ministry of Education, Brunei Darussalam.
Isolation and characterization of ssDNA aptamers against BipD antigen of Burkholderia pseudomallei

Selvam K, Najib MA, Khalid MF, Yunus MH, Wahab HA, Harun A, et al.

Anal Biochem, 2024 Aug 28;695:115655.
PMID: 39214325 DOI: 10.1016/j.ab.2024.115655

BACKGROUND: Melioidosis is difficult to diagnose due to its wide range of clinical symptoms. The culture method is time-consuming and less sensitive, emphasizing the importance of rapid and accurate diagnostic tests for melioidosis. Burkholderia invasion protein D (BipD) of Burkholderia pseudomallei is a potential diagnostic biomarker. This study aimed to isolate and characterize single-stranded DNA aptamers that specifically target BipD.
METHODS: The recombinant BipD protein was produced, followed by isolation of BipD-specific aptamers using Systematic Evolution of Ligands by EXponential enrichment. The binding affinity and specificity of the selected aptamers were evaluated using Enzyme-Linked Oligonucleotide Assay.
RESULTS: The fifth SELEX cycle showed a notable enrichment of recombinant BipD protein-specific aptamers. Sequencing analysis identified two clusters with a total of seventeen distinct aptamers. AptBipD1, AptBipD13, and AptBipD50 were chosen based on their frequency. Among them, AptBipD1 exhibited the highest binding affinity with a Kd value of 1.0 μM for the recombinant BipD protein. Furthermore, AptBipD1 showed significant specificity for B. pseudomallei compared to other tested bacteria.
CONCLUSION: AptBipD1 is a promising candidate for further development of reliable, affordable, and efficient point-of-care diagnostic tests for melioidosis.
Development of N-alkylated benzimidazole based cubosome hydrogel for topical treatment of burns

Nawaz M, Hayat S, Farooq U, Iqbal MA, Khalid SH, Nee TW, et al.

RSC Adv, 2024 Oct 09;14(44):32008-32020.
PMID: 39391623 DOI: 10.1039/d4ra04816d

The current study focuses on assessing the activity of the N-alkylated benzimidazole based cubosomal hydrogel (cubogel) for the topical treatment of burn wounds. The study involves the synthesis of six benzimidazole derivatives (1-6) and their characterization by FT-IR and 1H and 13C NMR spectroscopy. The further study involves the design and formation of nanoparticles known as cubosomes loaded with selected 1-benzyl-1-benzimidazole (API 6) and the development of a cubogel for the topical treatment of burn wounds. Cubosomes were prepared by the homogenization method, using glyceryl monooleate (GMO) as a lipid polymer and poloxamer 407 (P407) as a surfactant. Cubosomes undergo in vitro characterizations (measurement of particle size, zeta potential, polydispersity index (PDI), % entrapment efficiency, drug release in phosphate buffer saline of pH 6.8, and surface morphology by utilizing TEM (transmission electron microscopy). Formulation D3 (2.5% of GMO, 1% of P407, and 2.5% of PVA) emerged as the optimized formulation, displaying a minimum particle size (PS) of 129.9 ± 1 nm, entrapment efficiency (%EE) of 96.67 ± 0.89%, and a drug release of 86 ± 2.7% at 24 h. Carbopol 940 hydrogel was prepared and incorporated with the optimized formulation to prepare cubogel. This optimized cubogel provided 92.56 ± 0.014% in vitro drug release within 24 h. An in vivo histopathological study was conducted on an animal model (rabbit) to assess the efficacy of cubogel in wound healing and wound contraction. Then cubogel was compared with the commercially available creams Clotrimazole® and Polyfax®. The wound treated with newly developed cubogel has maximum wound contraction (96.70%) as compared to the standard creams. The findings revealed that the newly formulated cubogel was highly effective in treating burns, showing superior performance to commercial products without inducing side effects. Additionally, benzimidazole derivative loaded cubogel caused a sustained release for treating burn wounds without any bacterial infections. The current results further suggested phase 0 clinical trials.
Rheological and chemical properties of reclaimed asphalt pavement using polyethylene terephthalate (PET) additive as a modifier

Odubela CA, Yaacob H, Warid MNBM, Karim KJA, Kamaruddin NHBM, Al-Saffar ZH, et al.

Environ Sci Pollut Res Int, 2025 Mar;32(13):8025-8034.
PMID: 40048063 DOI: 10.1007/s11356-025-36193-x

Utilizing waste materials and reclaimed asphalt pavement (RAP) in road construction is gaining research interest. The pricey nature of building roads is attributed to the energy required for new material production and its environmental impact. The study investigated rheological and chemical properties of reclaimed asphalt pavement using PET additive as a modifier. The materials used in this study are virgin bitumen (VB), RAP bitumen (RB), and PET bottles. The synthesis of PET bottle into PET-derived additives was carried out, using aminolysis method in the presence of triethylenetriamine (TETA) as a solvent. Additionally, polymer-modified bitumen (PMB) was created by adding 2% PET additive with VB. The findings showed that utilizing PMB with RB in asphalt blend improved RB's brittle effect and has high resistance to deformation at high temperature. Moreover, the effect of the PMB on the asphalt binder did not alter the functional group while there was a reduced mass loss for PMB. Consequently, PET additives can be used to improve the quality of asphalt mixture in road construction, thus enhancing sustainability.
Accelerating crop improvement via integration of transcriptome-based network biology and genome editing

Razalli II, Abdullah-Zawawi MR, Tamizi AA, Harun S, Zainal-Abidin RA, Jalal MIA, et al.

Planta, 2025 Mar 17;261(4):92.
PMID: 40095140 DOI: 10.1007/s00425-025-04666-5

Big data and network biology infer functional coupling between genes. In combination with machine learning, network biology can dramatically accelerate the pace of gene discovery using modern transcriptomics approaches and be validated via genome editing technology for improving crops to stresses. Unlike other living things, plants are sessile and frequently face various environmental challenges due to climate change. The cumulative effects of combined stresses can significantly influence both plant growth and yields. In navigating the complexities of climate change, ensuring the nourishment of our growing population hinges on implementing precise agricultural systems. Conventional breeding methods have been commonly employed; however, their efficacy has been impeded by limitations in terms of time, cost, and infrastructure. Cutting-edge tools focussing on big data are being championed to usher in a new era in stress biology, aiming to cultivate crops that exhibit enhanced resilience to multifactorial stresses. Transcriptomics, combined with network biology and machine learning, is proving to be a powerful approach for identifying potential genes to target for gene editing, specifically to enhance stress tolerance. The integration of transcriptomic data with genome editing can yield significant benefits, such as gaining insights into gene function by modifying or manipulating of specific genes in the target plant. This review provides valuable insights into the use of transcriptomics platforms and the application of biological network analysis and machine learning in the discovery of novel genes, thereby enhancing the understanding of plant responses to combined or sequential stress. The transcriptomics as a forefront omics platform and how it is employed through biological networks and machine learning that lead to novel gene discoveries for producing multi-stress-tolerant crops, limitations, and future directions have also been discussed.
Integrating geostatistics and landsat-8 OLI imagery for regional-scale spatial mapping and remote assessment of soil and foliar nitrogen status in citrus agroecosystem

Ahmed H, Hameed MA, Javed N, Yousra M, Niaz M, Baloch B, et al.

Environ Geochem Health, 2026 Aug 19;48(13).
PMID: 42618830 DOI: 10.1007/s10653-026-03435-x

Nitrogen (N) deficiency and inefficient fertilizer use pose serious challenges to sustainable citrus production in Pakistan, particularly in major citrus-growing regions such as Sargodha. This study integrated pedometric mapping, geostatistics, and satellite remote sensing to diagnose the nitrogen status of citrus orchards in District Sargodha, Pakistan. Geo-referenced soil samples were collected from 90 orchard sites at three depths (0-20, 20-40, and 40-60 cm) and analyzed for plant-available nitrate-N (NO3--N), while diagnostic leaf samples were analyzed for total nitrogen content. Spatial variability was assessed using semivariogram modeling and ordinary kriging to generate digital nutrient distribution maps. Landsat-8 OLI imagery was used to compute 43 vegetation indices (VIs) involving two and three spectral bands, and their relationships with soil NO3--N and foliage N were evaluated through correlation and regression analyses. Results revealed widespread deficiency of plant-available NO₃⁻-N in soils and total N in foliage across the study area. Surface soil NO3--N showed significant positive relationships with deeper soil layers, indicating that surface soil analysis can reliably predict N availability within the 0-60 cm soil profile. Geostatistical analysis indicated moderate to strong spatial dependence for soil NO3--N and strong spatial dependence for foliage N content. Several vegetation indices, particularly Ratio Vegetation Indices (RVI-1, RVI-2, RVI-3), NDVI-based indices, and soil-adjusted indices, exhibited strong correlations with both soil NO3--N and foliage N, explaining up to 70% of variability. The findings demonstrate the strong potential of combining pedometric mapping and Landsat-based remote sensing for regional-scale diagnosis of nitrogen status in citrus orchards, providing a foundation for site-specific and precision nitrogen management strategies.
A novel classical machine learning framework for early sepsis prediction using electronic health record data from ICU patients

Prithula J, Islam KR, Kumar J, Tan TL, Reaz MBI, Rahman T, et al.

Comput Biol Med, 2025 Jan;184:109284.
PMID: 39579661 DOI: 10.1016/j.compbiomed.2024.109284

Sepsis, a life-threatening condition triggered by the body's response to infection, remains a significant global health challenge, annually affecting millions in the United States alone with substantial mortality and healthcare costs. Early prediction of sepsis is critical for timely intervention and improved patient outcomes. This study introduces an innovative predictive model leveraging machine learning techniques and a specific data-splitting approach on highly imbalanced electronic health records (EHRs). Using PhysioNet/CinC Challenge 2019 data from 40,336 patients, including vital signs, lab values, and demographics. Preliminary assessments using classical and stacked ML models with Synthetic Minority Oversampling Technique (SMOTE) augmentation were conducted, showing improved performance. It is found that stacking ML models enhances overall accuracy but faces limitations in precision, recall, and F1 score for positive class prediction. A novel data-splitting approach with 5-fold cross-validation and SMOTE and COPULA augmentation techniques demonstrated promise, with F1 scores ranging from 93 % to 94 % using the COPULA technique. COPULA excelled at predictions for different hours' onsets compared to the SMOTE technique. The proposed model outperformed existing studies, suggesting clinical viability for early sepsis prediction.
Fulltext Neurological Sequelae of Post-COVID-19 Fatigue: A Narrative Review of Dipeptidyl Peptidase IV-Mediated Cerebrovascular Complications

Che Mohd Nassir CMN, Che Ramli MD, Jaffer U, Abdul Hamid H, Mehat MZ, Mohamad Ghazali M, et al.

Curr Issues Mol Biol, 2024 Nov 28;46(12):13565-13582.
PMID: 39727939 DOI: 10.3390/cimb46120811

Coronavirus disease 2019 (COVID-19) has been a global pandemic affecting millions of people's lives, which has led to 'post-COVID-19 fatigue'. Alarmingly, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) not only infects the lungs but also influences the heart and brain. Endothelial cell dysfunction and hypercoagulation, which we know occur with this infection, lead to thrombo-inflammation that can manifest as many myriad cardio-cerebrovascular disorders, such as brain fog, fatigue, cognitive dysfunction, etc. Additionally, SARS-CoV-2 has been associated with oxidative stress, protein aggregation, cytokine storm, and mitochondrial dysfunction in neurodegenerative diseases. Accordingly, the identification of molecular targets involved in these actions could provide strategies for preventing and treating this disease. In particular, the very common enzyme dipeptidyl peptidase IV (DPPIV) has recently been identified as a candidate co-receptor for the cell entry of the SARS-CoV-2 virus with its involvement in infection. In addition, DPPIV has been reported as a co-receptor for some viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV). It mediates immunologic reactions and diseases such as type 2 diabetes mellitus, obesity, and hypertension, which have been considered the prime risk factors for stroke among other types of cardio-cerebrovascular diseases. Unlike angiotensin-converting enzyme 2 (ACE2), DPPIV has been implicated in aggravating the course of infection due to its disruptive effect on inflammatory signaling networks and the neuro-glia-vascular unit. Regarding the neurological, physiological, and molecular grounds governing post-COVID-19 fatigue, this review focuses on DPPIV as one of such reasons that progressively establishes cerebrovascular grievances following SARS-CoV infection.
Phytochemical Profiling and Biological Activities of Nigella sativa Vinegar Extract: An Insight Into Hypoglycemic Potential Using In Vivo and In Silico Studies

Akhtar MT, Qadir R, Altaf U, Almas T, Batool S, Ikram MS, et al.

Chem Biodivers, 2024 Dec 29.
PMID: 39804576 DOI: 10.1002/cbdv.202402512

The current study was conducted to characterize the vinegar extract of Nigella sativa and evaluate its biological activities using in vitro and in vivo studies. The N. sativa extract (NSE) was prepared by macerating seeds in a mixture of water and synthetic vinegar (1:10). The antioxidant potential of NSE was assessed, revealing high total phenolic contents (431.66 mg/100 g), total flavonoid contents (73.45 mg/100 g), total antioxidant capacity (118.55 mg/100 g), and strong radical scavenging potential (89.67%). The anticancer activity of NSE showed insignificant cytotoxic effects on HepG2 liver cell lines (96.61 ± 3.00). An in vivo animal trial was performed, and NSE significantly (p
Fulltext Benchmarking the high conductive two-dimensional layered structured NbS2, ZrS2, ReS2 and NbSe2 materials with zero energy bandgap (E g) for photocatalytic application: a DFT study

Jameel MH, Yasin A, Tuama AN, Jabbar AH, Kousar S, Mayzan MZH, et al.

R Soc Open Sci, 2025 Mar;12(3):241560.
PMID: 40061220 DOI: 10.1098/rsos.241560

Two-dimensional materials are among the most scientifically accessible materials in material science at the beginning of the twenty-first century. There has been interest in the monolayer transition metal dichalcogenide (TMDC) family because of its large active site surface area for UV photons of light for wastewater treatment. In the present work, density functional theory (DFT) is utilized to model the optical, structural and electrical properties of TMDCs such as NbS2, ZrS2, ReS2 and NbSe2 using the GGA-PBE simulation approximation. Based on DFT calculations, it is determined that NbS2, ZrS2, ReS2 and NbSe2 have zero energy bandgap (E g). The additional gamma-active states that are generated in NbS2, ZrS2, ReS2 and NbSe2 materials aid in the construction of the conduction and valence bands, resulting in a zero E g. In the ultraviolet (UV) spectrum, the increase in optical conductance peaks from 4.5 to 15.7 suggests that the material exhibits stronger absorption or interaction with UV light due to the excitation of electronic transitions or inter-band transitions. The highest optical conductivity and absorbance of two-dimensional TMDCs NbS2, ZrS2, NbSe2 and ReS2 show 2.4 × 105, 2.5 × 105, 2.8 × 105 and 7 × 105 Ω - 1 c m - 1 , respectively. The TMDC family, including two-dimensional TMDCs NbS2, ZrS2, NbSe2 and ReS2, is known for its unique electronic and optical properties. Their layered structure and high surface area make them excellent candidates for applications involving light absorption and photodetection. These materials reduce photon recombination and improve charge transport, making them suitable for photocatalytic and photoanode applications.
Fulltext Fracture resistance of mandibular molar endocrown with different preparation designs: an in vitro study

Awang Iskanderdzulkarnein PMB, Raja Mohd N, Ahmad Ubaidillah AH, Noor Zari MAI, Ahmad SF, Sulaiman E

PeerJ, 2026;14:e21801.
PMID: 42928894 DOI: 10.7717/peerj.21801

BACKGROUND: Endocrowns have gained popularity as a conservative option for restoring endodontically treated molars because their success rates are comparable to those of conventional crowns. However, there is limited evidence on the effectiveness of different endocrown marginal designs, particularly concerning their fracture resistance and failure modes under axial and oblique loading. This in vitro study aimed to evaluate the fracture resistance and failure modes of three different endocrown marginal designs on mandibular molars and compare them with endocrowns under axial and oblique loading.
METHODS: Sixty-four extracted mandibular molars were root-treated and lined with flowable composite (1.5 mm thickness) before being embedded in epoxy resin blocks. The samples were divided into four groups (n = 16): three endocrown groups with different preparation designs (butt-joint, 0.8 mm chamfer, and 1.0 mm shoulder) and one group with conventional crowns. Crown preparations were performed with a high-speed handpiece mounted on a modified milling device, targeting a 2.0 mm anatomical occlusal reduction for conventional crowns and a 4.0 mm central chamber depth with a 2.0 mm axial wall height (ferrule) for endocrowns (except the butt-joint design, which had no ferrule preparation). Restorations were fabricated using the Chairside Economical Restoration of Esthetic Ceramics (CEREC) Computer-Aided Design and Computer-Aided Manufacturing (CAD/CAM) system with lithium disilicate (IPS e.max CAD; minimum occlusal thickness: 1.5 mm) as the restorative material and cemented with the RelyX Ultimate dual-cure resin adhesive. After 1,500 thermocycling cycles, the samples were divided into two subgroups (n = 8) for axial and oblique loading tests. The fracture resistance was tested using a universal testing machine at a crosshead speed of 0.5 mm/min, applying a load of up to 5,000 N until fracture. Failure modes were examined using a stereomicroscope at 5x magnification and categorized as catastrophic or non-catastrophic. The mean fracture resistance was compared using one-way Analysis of Variance (ANOVA) with Bonferroni post-hoc tests, and Fisher's exact test was used to assess the association between preparation designs and failure modes (p < 0.05).
RESULTS: Endocrowns with shoulder margins showed significantly higher fracture resistance (3,042.83 ± 850.76 N) than conventional crowns (1,908.28 ± 635.82 N) under axial loading (p = 0.02). No significant differences were found under oblique loading between the preparation designs. The preparation design significantly influenced the failure mode under axial loading (p = 0.049). Endocrowns exhibited a higher rate of catastrophic fractures than conventional crowns, regardless of loading direction.
CONCLUSIONS: Endocrowns provide a conservative alternative to conventional crowns, offering a higher fracture resistance under axial loading. Further research is needed to evaluate the endocrown performance under oblique loading.
Mechanisms of β-adrenergic receptors agonists in mediating pro and anti-apoptotic pathways in hyperglycemic Müller cells

Safi SZ, Saeed L, Shah H, Latif Z, Ali A, Imran M, et al.

Mol Biol Rep, 2022 Oct;49(10):9473-9480.
PMID: 35925485 DOI: 10.1007/s11033-022-07816-0

BACKGROUND: The current study aimed to investigate the stimulatory effect of beta-adrenergic receptors (β-ARs) on brain derived neurotropic factor (BDNF) and cAMP response element binding protein (CREB).
METHODS: Human Müller cells were cultured in low and high glucose conditions. Cells were treated with xamoterol (selective agonist for β1-AR), salmeterol (selective agonist for β2-AR), isoproterenol (β-ARs agonist) and propranolol (β-ARs antagonist), at 20 µM concentration for 24 h. Western Blotting assay was performed for the gene expression analysis. DNA damage was evaluated by TUNEL assay. DCFH-DA assay was used to check the level of reactive oxygen species (ROS). Cytochrome C release was measured by ELISA.
RESULTS: Xamoterol, salmeterol and isoproterenol showed no effect on Caspase-8 but it reduced the apoptosis and increased the expression of BDNF in Müller cells. A significant change in the expression of caspase-3 was observed in cells treated with xamoterol and salmeterol as compared to isoproterenol. Xamoterol, salmeterol and isoproterenol significantly decreased the reactive oxygen species (ROS) when treated for 24 hours. Glucose-induced cytochrome c release was disrupted in Müller cells.
CONCLUSION: β-ARs, stimulated by agonist play a protective role in hyperglycemic Müller cells, with the suppression of glucose-induced caspase-3 and cytochrome c release. B-Ars may directly mediate the gene expression of BDNF.
Suppression of miR426 enhances photoprotection and chlorophyll stability via upregulation of ELIP2 in Arabidopsis thaliana

Mustaffa AF, Othman SMIS, Mohd Zahid NII, Hafiz Che-Othman M, Goh HH, Sajad M, et al.

Mol Biol Rep, 2026 Jan 03;53(1):248.
PMID: 41483062 DOI: 10.1007/s11033-025-11306-4

BACKGROUND: Plants require light energy to undergo photosynthesis, a process that is essential for their growth and development. However, excessive light can lead to photooxidative stress and photoinhibition, compromising key photosynthetic components, particularly chlorophyll pigments. Early light-induced protein 2 (ELIP2) plays a key role in photoprotection by suppressing chlorophyll biosynthesis, preventing chlorophyll bleaching, and enhancing photosynthetic efficiency. The expression of ELIP2 is regulated through multiple mechanisms, including post-transcriptional and translational controls. This study aims to elucidate the role of plant microRNA (miRNA) in regulating ELIP2 gene activity at the post-transcriptional level, thereby enhancing plant defence mechanisms and maintaining chlorophyll stability under conditions of photooxidative stress and photoinhibition. METHODS AND RESULTS: An in silico analysis identified miR426 as a key post-transcriptional regulator of ELIP2. Using short tandem target mimic (STTM), transgenic Arabidopsis thaliana plants constitutively expressing STTM426 were developed and exposed to varying light intensities alongside wild type (WT) plants. Expression profiling revealed a significant reduction in miR426 levels and increased ELIP2 transcript abundance in transgenic plants compared to WT (n = 3). Interestingly, transgenic plants displayed minimal changes in chlorophyll content under normal light and maintained stability even under extreme light conditions (n = 9). Gas exchange and chlorophyll a fluorescence analyses further demonstrated enhanced photosynthetic efficiency and photoprotective mechanisms in the transgenic plants (n = 9). These physiological improvements were supported by morphological observations, as transgenic plants consistently exhibited reduced rosette diameter and total biomass across all light intensities (n = 9). CONCLUSION: These preliminary findings suggest that suppression of miR426 may serve as a promising strategy to enhance plant resilience against photooxidative and photoinhibitory stress by strengthening photoprotective mechanisms and maintaining chlorophyll stability.
Hydrazinyl arylthiazole based pyridine scaffolds: Synthesis, structural characterization, in vitro α-glucosidase inhibitory activity, and in silico studies

Ali F, Khan KM, Salar U, Taha M, Ismail NH, Wadood A, et al.

Eur J Med Chem, 2017 Sep 29;138:255-272.
PMID: 28672278 DOI: 10.1016/j.ejmech.2017.06.041

Acarbose, miglitol, and voglibose are the inhibitors of α-glucosidase enzyme and being clinically used for the management of type-II diabetes mellitus. However, many adverse effects are also associated with them. So, the development of new therapeutic agents is an utmost interest in medicinal chemistry research. Current study is based on the identification of new α-glucosidase inhibitors. For that purpose, hydrazinyl arylthiazole based pyridine derivatives 1-39 were synthesized via two step reaction and fully characterized by spectroscopic techniques EI-MS, HREI-MS, (1)H-, and (13)C NMR. However, stereochemistry of the iminic bond was confirmed by NOESY. All compounds were subjected to in vitro α-glucosidase inhibitory activity and found many folds active (IC50 = 1.40 ± 0.01-236.10 ± 2.20 μM) as compared to the standard acarbose having IC50 value of 856.45 ± 5.60 μM. A limited structure-activity relationship was carried out in order to make a presumption about the substituent's effect on inhibitory activity which predicted that substituents of more negative inductive effect played important role in the activity as compared to the substituents of less negative inductive effect. However, in order to have a good understanding of ligand enzyme interactions, molecular docking study was also conducted. In silico study was confirmed that substituents like halogens (Cl) and nitro (NO2) which have negative inductive effect were found to make important interactions with active site residues.
Fulltext Employment of single-diode model to elucidate the variations in photovoltaic parameters under different electrical and thermal conditions

Muhammad FF, Yahya MY, Hameed SS, Aziz F, Sulaiman K, Rasheed MA, et al.

PLoS One, 2017;12(8):e0182925.
PMID: 28793325 DOI: 10.1371/journal.pone.0182925

In this research work, numerical simulations are performed to correlate the photovoltaic parameters with various internal and external factors influencing the performance of solar cells. Single-diode modeling approach is utilized for this purpose and theoretical investigations are compared with the reported experimental evidences for organic and inorganic solar cells at various electrical and thermal conditions. Electrical parameters include parasitic resistances (Rs and Rp) and ideality factor (n), while thermal parameters can be defined by the cells temperature (T). A comprehensive analysis concerning broad spectral variations in the short circuit current (Isc), open circuit voltage (Voc), fill factor (FF) and efficiency (η) is presented and discussed. It was generally concluded that there exists a good agreement between the simulated results and experimental findings. Nevertheless, the controversial consequence of temperature impact on the performance of organic solar cells necessitates the development of a complementary model which is capable of well simulating the temperature impact on these devices performance.
p16 Tumor Suppressor Gene Methylation in Diffuse Large B Cell Lymphoma: A Study of 88 Cases at Two Hospitals in the East Coast of Malaysia

Mohd Ridah LJ, A Talib N, Muhammad N, Hussain FA, Zainuddin N

Asian Pac J Cancer Prev, 2017 10 26;18(10):2781-2785.
PMID: 29072413

Introduction: p16 gene plays an important role in the normal cell cycle regulation. Methylation of p16 has been reported to be one of the epigenetic events contributing to the pathogenesis of diffuse large B-cell lymphoma (DLBCL) which occurring at varying frequency. DLBCL is an aggressive and high-grade malignancy which accounts for approximately 30% of all non-Hodgkin lymphoma cases. However, little is known regarding the epigenetic alterations of p16 gene in DLBCL cases in Malaysia. Therefore, the objective of this study was to examine the status of p16 methylation in DLBCL. Methods: A total of 88 formalin-fixed paraffin-embedded DLBCL tissues retrieved from two hospitals located in the east coast of Malaysia, namely Hospital Tengku Ampuan Afzan (HTAA) Pahang and Hospital Universiti Sains Malaysia (HUSM) Kelantan, were chosen for this study. DNA specimens were isolated and subsequently subjected to bisulfite treatment prior to methylation specific-PCR. Two pairs of primers were used to amplify methylated and unmethylated regions of p16 gene. The PCR products were then separated using agarose gel electrophoresis and visualised under UV illumination. SPSS version 12.0 was utilised to perform all statistical analysis. Result: p16 methylation was detected in 65 of 88 (74%) samples. There was a significant association between p16 methylation status and patients aged >50 years old (p=0.04). Conclusion: Our study demonstrated that methylation of p16 tumor suppressor gene in our DLBCL cases is common and significantly increased among patients aged 50 years and above. Aging is known to be an important risk factor in the development of cancers and we speculate that this might be due to the increased transformation of malignant cells in aging cell population. However, this has yet to be confirmed with further research and correlate the findings with clinicopathological parameters.
Fulltext Prevalence and management of anemia in pre-dialysis Malaysian patients: A hospital-based study

Salman M, Khan AH, Adnan AS, Sulaiman SA, Hussain K, Shehzadi N, et al.

Rev Assoc Med Bras (1992), 2016 Nov;62(8):742-747.
PMID: 27992014 DOI: 10.1590/1806-9282.62.08.742

Objective:: Anemia, a common complication of chronic kidney diseases (CKD), is involved in significant cardiovascular morbidity. Therefore, the objective of our study was to investigate the prevalence and severity of anemia in pre-dialysis patients, as well as to determine the predictors of anti-anemic therapy.
Method:: A retrospective, observational study was conducted on adult pre-dialysis patients receiving treatment at the Hospital Universiti Sains Malaysia from January 2009 to December 2013.
Results:: A total of 615 eligible cases were included. The mean age of patients was 64.1±12.0 years. The prevalence of anemia was 75.8%, and the severity of anemia was mild in 47.7% of the patients, moderate in 32.2%, and severe in 20%. Based on morphological classification of anemia, 76.9% of our patients had normochromic-normocytic anemia whereas 21.8 and 1.3% had hypochromic-microcytic anemia and macrocytic anemia, respectively. Oral iron supplements were prescribed to 38.0% of the patients and none of the patients was given erythropoietin stabilizing agents (ESA) or intravenous iron preparations. In logistic regression, significant predictors of anti-anemic preparation use were decreased hemoglobin and hematocrit, and advanced stages of CKD.
Conclusion:: The results of the present study suggest that the prevalence of anemia in pre-dialysis patients is higher than currently accepted and it is found to be correlated with renal function; prevalence increases with declined renal function. An earlier identification as well as appropriate management of anemia will not only have a positive impact on quality of life but also reduce hospitalizations of CKD patients due to cardiovascular events.
Computational study of structural, optoelectronic and nonlinear optical properties of dynamic solid-state chalcone derivatives

Chaudhry AR, Irfan A, Muhammad S, Al-Sehemi AG, Ahmed R, Jingping Z

J Mol Graph Model, 2017 08;75:355-364.
PMID: 28651184 DOI: 10.1016/j.jmgm.2017.05.012

In the present study, we use the state of art density functional theory (DFT) techniques to calculate the structural, optoelectronic and nonlinear optical (NLO) properties for two novel chalcone derivatives. The geometrical structures of chalcone derivatives compound 1 and 2 are optimized using periodic boundary conditions (PBC) in solid-state phase as well as isolated single molecular geometry in the gas phase. The reasonable agreement is found among experimental, solid-state and gas phase single molecular geometries, which provide us, further confidence to explore the potential of above-entitled derivatives as good functional materials for electro-optical applications. For instance, the frequency dependent real parts of dielectric functions are calculated for compound 1 and 2. The maximum value of real part of the dielectric function for compound 1 and 2 at 0eV are computed as 4.35 and 6.68 for the polarization vectors of (001) directions, respectively, which reveals the fact that the compound 1 and 2 might be good charge transport materials. The reflectivities of the compound 1 and 2 are 0.64 and 0.45 revealing that the compound 2 might be more efficient material for organic photovoltaic (OPV) applications. The results of the refractive index improved by doping the strong electron withdrawing groups (EWGs) shows that the compound 2 might be good refractor of the photon as compared to compound 1. The calculated values for static second-order polarizability are 3498 and 10464 a. u. and for frequency dependent second harmonic generations are 2557 and 6429 a. u. for compound 1 and 2, respectively, which indicates their significant potential for possible nonlinear optical applications.
Synthesis, molecular docking study and thymidine phosphorylase inhibitory activity of 3-formylcoumarin derivatives

Taha M, Adnan Ali Shah S, Afifi M, Imran S, Sultan S, Rahim F, et al.

Bioorg Chem, 2018 08;78:17-23.
PMID: 29525348 DOI: 10.1016/j.bioorg.2018.02.028

Thymidine phosphorylase (TP) over expression plays role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. The inhibitor of this enzyme plays an important role in preventing the serious threat due to over expression of TP. In this regard, a series of seventeenanalogs of 3-formylcoumarin (1-17) were synthesized, characterized by 1HNMR and EI-MS and screened for thymidine phosphorylaseinhibitory activity. All analogs showed a variable degree of thymidine phosphorylase inhibition with IC50 values ranging between 0.90 ± 0.01 and 53.50 ± 1.20 μM when compared with the standard inhibitor 7-Deazaxanthine having IC50 value 38.68 ± 1.12 μM. Among the series, fifteenanalogs such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16 and 17 showed excellent inhibition which is many folds better than the standard 7-Deazaxanthine whiletwo analogs 13 and 14 showed good inhibition. The structure activity relationship (SAR) was mainly based upon by bring about difference of substituents on phenyl ring. Molecular docking study was carried out to understand the binding interaction of the most active analogs.

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