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Islamic Perspectives on CRISPR/Cas9-Mediated Human Germline Gene Editing: A Preliminary Discussion

Isa NM, Zulkifli NA, Man S

Sci Eng Ethics, 2020 02;26(1):309-323.
PMID: 30830592 DOI: 10.1007/s11948-019-00098-z

The recent development of CRISPR/Cas9 technology has rekindled the ethical debate concerning human germline modification that has begun decades ago. This inexpensive technology shows tremendous promise in disease prevention strategies, while raising complex ethical concerns about safety and efficacy of the technology, human dignity, tampering with God's creation, and human genetic enhancement. Germline gene editing may result in heritable changes in the human genome, therefore the question of whether it should be allowed requires deep and careful discussion from various perspectives. This paper explores Islamic perspectives on the concerns raised and highlights the ethical principles in Islam that should be taken into consideration when assessing the permissibility of CRISPR/ Cas9-mediated human germline gene editing. As argued in this paper, human germline gene editing would be considered lawful for medical purpose under certain conditions. It should not be applied on humans until the safety and efficacy issues are resolved. Robust ethical guidelines and strict regulations are necessary to preserve human dignity and to prevent premature and misuse of the technology. Maqasid al-shariah's principles of preservation of human life, lineage, and dignity and 'preventing harm takes precedence over securing benefit' are among the guiding principles in assessing the permissibility of CRISPR/Cas9-mediated human germline editing from an Islamic perspective. Further discussions are important to address the controversies as well as to explore the related ethical principles.
Anti-diabetic medication burden amongst older persons with diabetes and associated quality of life

Shalihin SE, Fauzi A, Zulkifli NA, Aziz AA

Med J Malaysia, 2020 09;75(5):525-530.
PMID: 32918421

BACKGROUND: Older persons with diabetes are the major demographic of diabetic patients followed up in primary health clinics. Despite their increasing age and morbidities, they are still being managed strictly towards good sugar control in order to achieve the ideal HbA1c level without taking their quality of life into consideration. This study aimed to determine the prevalence in the use of antidiabetic drugs among older persons with diabetes and its association with their quality of life.
METHODOLOGY: A cross-sectional study was conducted among 269 older persons with diabetes in all government health clinics in Kuantan using Diabetes Quality of Life questionnaire. SPSS version 23 was used for the statistical analysis.
RESULTS: Majority of the respondents were females (61%), Malays (84.8%), pensioners (54.3%) with education up to primary school (52%) and are staying with family members (93.7%). Most of the patients were on two antidiabetic agents (48%) followed by a single antidiabetic agent (32%). Despite the risk of hypoglycaemia, 0.4% of them are on glibenclamide. The use of insulin is still common among 21% of them that are on intermediate-acting insulin, 15.6% on premixed insulin and 7.8% on short-acting insulin. Those taking a higher number of antidiabetic agents were found to be associated with poorer quality of life (p=0.001) compared to those taking one or two antidiabetic medications. Those on insulin also have significantly poorer quality of life score (p=0.012).
CONCLUSION: Despite aiming for controlled diabetes, older persons suffer poor quality of life with further intensification of their antidiabetic medications according to the guidelines. This includes the complexity of insulin usage and polypharmacy, which contribute to the low quality of life score.
EMT markers gene expression in BPIFB2 overexpressed gastric cancer cell lines

Karim Z, Zulkifli NA, Sheikh Abdul Kadir SH, Abd Khalil K, Musa M

Ann Oncol, 2018 Nov;29 Suppl 9:ix55.
PMID: 32178067 DOI: 10.1093/annonc/mdy432.026
Clinical outcomes of children with COVID-19 infection in a low-risk centre in Malaysia

Tan MS, Zulkifli NA, Teng W, Lim PT

Med J Malaysia, 2023 Dec;78(7):853-856.
PMID: 38159917

INTRODUCTION: According to WHO, long-COVID or post- COVID-19 condition is defined as the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. A systematic review and meta-analyses published in 2022, which mainly focus on the Western population, revealed that the prevalence of long COVID was 25.24%. Literature regarding long-COVID in children in Asia was scarce. The objectives of our study were to assess the long-term effect of COVID-19 infection in children and its correlation to their acute COVID- 19 infection.
MATERIALS AND METHODS: This study was conducted in Hospital Kepala Batas (HKB), a district hospital in Penang State, Malaysia, which was the designated regional COVID hospital during the pandemic. It was a retrospective observational study, where children who were admitted from November 2020 to March 2021, and attended follow-up clinics from Jan 2021 to May 2021, were recruited.
RESULTS: This study comprised 90 subjects, from 3 months old to 12 years old, mean of 6.5 years old. When comparing asymptomatic and symptomatic children, children with comorbidities were more likely to be symptomatic with a pvalue of 0.045 using the Pearson Chi-square test. All our patients' symptoms resolved upon discharge. During followup at 2-4 months after COVID-19 infection, all children were reported as back to their usual selves. Fifteen patients had recurrent symptoms. Most of their symptoms pointed towards an acute infection. One patient had two episodes of illness, while the rest had one. The most common symptoms were cough, fever and runny nose. The average duration of illness of these 16 episodes was 4.5 days with a standard deviation of 2.48. None of these symptoms lasted more than seven days. None of them required hospital admission. None of them had recurrent COVID-19 infections. Tweleve out of 72 children who had been going to school stopped physical school after COVID-19 infection. Our findings differed from other studies. These could be due to the limitations that we faced.
CONCLUSION: Most children who contracted COVID-19 infection recovered fully after acute infection, and most of them recovered fully without long-term sequelae.
Fulltext Psychosocial Factors Associated with Depression and Anxiety During COVID-19 Pandemic Among Outpatients with Depression

Zulkifli NA, Guan NC, Zainal NZ, Ling TS

Alpha Psychiatry, 2021 Jul;22(4):185-193.
PMID: 36424937 DOI: 10.5152/alphapsychiatry.2021.21107

OBJECTIVE: Long-term social distancing, isolation, and economic fallout may be significant psychological triggers during pandemic, such as COVID-19, especially for those with underlying psychiatric illness. This study was conducted to address the psychological impact of COVID-19 pandemic among patients with depression based at a teaching hospital in Malaysia.
METHODS: This is a cross-sectional online study among patients with depression from University Malaya Medical Centre, using Generalized Anxiety Disorder-7 (GAD-7), Montgomery-Åsberg Depression Rating Scale-Self Assessment (MADRS-S), Insomnia Severity Index (ISI), Multidimensional Scale of Perceived Social Support (MSPSS), Knowledge, Attitudes, and Practices (KAP), and Social Media Addiction during COVID-19 Pandemic (SMACOP).
RESULTS: One hundred seventy-eight patients participated in this study. The mean total of the KAP score is 12.65 (SD = 2.65), with knowledge section (mean = 7.34 [SD = 2.13]), attitudes section (mean = 2.63 [SD = 0.58]), and practices section (mean = 2.69 [SD = 1.00]). They scored moderately on the MADRS-S (mean = 21.03 [SD = 4.62]) and ISI (mean = 20.25 [SD = 4.62]) but had high GAD-7 scores (mean = 16.8 (SD = 6.27]). From the multiple logistic regression analyses, depressive symptoms of greater severity (MADRS-S 18-34) are significantly associated with more severe insomnia (P < .001, adjusted OR = 9.101, 95% CI: 3.613-22.924). Furthermore, the high anxiety level is associated with the younger age group (P = .029, Adjusted OR = 2.274, 95% CI: 1.090-4.746), greater severity of insomnia (P < .001, Adjusted OR = 22.9, 95% CI: 6.145-85.343), and higher risk of COVID-19 related social media addiction (P = .011, adjusted OR = 2.637, 95% CI: 1.253-5.550).
CONCLUSION: This study demonstrates the high levels of sleep disturbances and anxiety symptoms experienced by outpatients with depression during the COVID-19 pandemic. These are closely linked to the younger age group and at-risk social media addiction related to COVID-19.
Impact of photoluminescent carbon quantum dots on photosynthesis efficiency of rice and corn crops

Tan TL, Zulkifli NA, Zaman ASK, Jusoh MB, Yaapar MN, Rashid SA

Plant Physiol Biochem, 2021 May;162:737-751.
PMID: 33799185 DOI: 10.1016/j.plaphy.2021.03.031

Photosynthesis is one of the most fundamental biochemical processes on earth such that it is vital to the existence of most lives on this planet. In fact, unravelling the potentials in enhancing photosynthetic efficiency and electron transfer process, which are thought to improve plant growth is one of the emerging approaches in tackling modern agricultural shortcomings. In light of this, zero-dimensional carbon quantum dots (CQD) have emerged and garnered much interest in recent years which can enhance photosynthesis by modulating the associated electron transfer process. In this work, CQD was extracted from empty fruit bunch (EFB) biochar using a green acid-free microwave method. The resulting CQD was characterized using HRTEM, PL, UV-Vis and XPS. Typical rice (C3) and corn (C4) crops were selected in the present study in order to compare the significant effect of CQD on the two different photosynthetic pathways of crops. CQD was first introduced into crop via foliar spraying application instead of localised placement of CQD before seedling development. The influence of CQD on the photosynthetic efficiency of rice (C3) and corn (C4) leaves was determined by measuring both carbon dioxide conversion and the stomatal conductance of the leaf. As a result, the introduction of CQD greatly enhanced the photosynthesis in CQD-exposed crops. This is the first study focusing on phylogenetically constrained differences in photosynthetic responses between C3 and C4 crops upon CQD exposure, which gives a better insight into the understanding of photosynthesis process and shows considerable promise in nanomaterial research for sustainable agriculture practices.
Fulltext Sequence variation data of the mitochondrial DNA D-loop region of the captive Malayan Gaur (Bos gaurus hubbacki)

Md-Zain BM, Abdul-Aziz A, Aifat NR, Mohd-Yusof NS, Zulkifli NA, Japning JRR, et al.

Data Brief, 2019 Jun;24:103532.
PMID: 31193484 DOI: 10.1016/j.dib.2018.11.117

This article contains data of the sequence variation in the mitochondrial DNA D-loop region of the Malayan gaur (Bos gaurus hubbacki), locally known as the seladang, from two captive centers. Thirty fecal samples of Malayan gaur were collected from Jenderak Selatan Wildlife Conservation Center (Pahang) and the Sungkai Wildlife Reserve (Perak) for DNA extraction and amplification with polymerase chain reactions. DNA sequences were then analyzed using neighbor joining (NJ) and maximum parsimony (MP) methods. Based on the 652 base pairs obtained, we found seven variable characters with a value of 1%. The genetic distance between the two captive centers was 0.001. Haplotype analyses detected only four haplotypes between these two captive centers. Both NJ and MP trees demonstrate that all individuals in the Jenderak and Sungkai captive centers are in the same clade. Genetic variation of the Malayan gaur in these centers is considered low, possibly because individuals share the same common parent. This sequence variation data are of paramount importance for designing a proper breeding and management program of the Malayan gaur in the future.
Fulltext The potential neuroprotective effects of stingless bee honey

Zulkifli NA, Hassan Z, Mustafa MZ, Azman WNW, Hadie SNH, Ghani N, et al.

Front Aging Neurosci, 2022;14:1048028.
PMID: 36846103 DOI: 10.3389/fnagi.2022.1048028

Tropical Meliponini bees produce stingless bee honey (SBH). Studies have shown beneficial properties, including antibacterial, bacteriostatic, anti-inflammatory, neurotherapeutic, neuroprotective, wound, and sunburn healing capabilities. High phenolic acid and flavonoid concentrations offer SBH its benefits. SBH can include flavonoids, phenolic acids, ascorbic acid, tocopherol, organic acids, amino acids, and protein, depending on its botanical and geographic origins. Ursolic acid, p-coumaric acid, and gallic acid may diminish apoptotic signals in neuronal cells, such as nuclear morphological alterations and DNA fragmentation. Antioxidant activity minimizes reactive oxygen species (ROS) formation and lowers oxidative stress, inhibiting inflammation by decreasing enzymes generated during inflammation. Flavonoids in honey reduce neuroinflammation by decreasing proinflammatory cytokine and free radical production. Phytochemical components in honey, such as luteolin and phenylalanine, may aid neurological problems. A dietary amino acid, phenylalanine, may improve memory by functioning on brain-derived neurotrophic factor (BDNF) pathways. Neurotrophin BDNF binds to its major receptor, TrkB, and stimulates downstream signaling cascades, which are crucial for neurogenesis and synaptic plasticity. Through BDNF, SBH can stimulate synaptic plasticity and synaptogenesis, promoting learning and memory. Moreover, BDNF contributes to the adult brain's lasting structural and functional changes during limbic epileptogenesis by acting through the cognate receptor tyrosine receptor kinase B (TrkB). Given the higher antioxidants activity of SBH than the Apis sp. honey, it may be more therapeutically helpful. There is minimal research on SBH's neuroprotective effects, and the related pathways contribute to it is unclear. More research is needed to elucidate the underlying molecular process of SBH on BDNF/TrkB pathways in producing neuroprotective effects.
Cu(II) complexes based on benzimidazole ligands: synthesis, characterization, DFT, molecular docking & bioactivity study

Hamali MA, Roney M, Dubey A, Uddin MN, Zulkifli NA, Fasihi Mohd Aluwi MF, et al.

Future Med Chem, 2024 Nov 12.
PMID: 39530504 DOI: 10.1080/17568919.2024.2419353

Aim: The biggest cause of cancer deaths globally was lung cancer. New cancer fighting drugs are needed due to the rising number of cancer patients and cancer cells' treatment resistance.Results: Two Cu(II) complexes, synthesized from ligands based on 2-aminomethyl benzimidazole and salicylaldehyde derivatives, were designed and evaluated for their effectiveness against A549 lung cancer. The compounds were subjected to computational calculation using Density Functional Theory (DFT) to gather information on their reactivity. Furthermore, molecular docking are utilized to simulate the interaction between the compound and the MPP-9 protein. The synthesis of the ligands and their Cu(II) metal complexes are efficient and straightforward. The complexation between copper atom and the ligand are in 1:1 ratio. The MTT assay of the compounds against A549 lung carcinoma reveals that the both Cu(II) complexes good cytotoxicity activity, in comparison to their respective ligands. The low HOMO-LUMO band gap based on the DFT calculation predicts the high reactivity of the compounds. Furthermore, the low binding energy and the numbers of interactions of the Cu(II) complexes with MMP-9 protein binding site coincide with the antiproliferative activity tested in vitro.Conclusion: The cytotoxicity studies performed for Cu(L1Br) are promising, indicating a good candidate for a future drug.
Fulltext A new subspecies identification and population study of the Asian small-clawed otter (Aonyx cinereus) in Malay Peninsula and southern Thailand based on fecal DNA method

Rosli MK, Syed-Shabthar SM, Abdul-Patah P, Abdul-Samad Z, Abdul SN, Burhanuddin MN, et al.

ScientificWorldJournal, 2014;2014:457350.
PMID: 24715812 DOI: 10.1155/2014/457350

Three species of otter can be found throughout Malay Peninsula: Aonyx cinereus, Lutra sumatrana, and Lutrogale perspicillata. In this study, we focused on the A. cinereus population that ranges from the southern and the east coast to the northern regions of Malay Peninsula up to southern Thailand to review the relationships between the populations based on the mitochondrial D-loop region. Forty-eight samples from six populations were recognized as Johor, Perak, Terengganu, Kelantan, Ranong, and Thale Noi. Among the 48 samples, 33 were identified as A. cinereus, seven as L. sumatrana, and eight as L. perspicillata. Phylogenetically, two subclades formed for A. cinereus. The first subclade grouped all Malay Peninsula samples except for samples from Kelantan, and the second subclade grouped Kelantan samples with Thai sample. Genetic distance analysis supported the close relationships between Thai and Kelantan samples compared to the samples from Terengganu and the other Malaysian states. A minimum-spanning network showed that Kelantan and Thailand formed a haplogroup distinct from the other populations. Our results show that Thai subspecies A. cinereus may have migrated to Kelantan from Thai mainland. We also suggest the classification of a new subspecies from Malay Peninsula, the small-clawed otter named A. cinereus kecilensis.

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