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  1. Wu R, Abdulhameed AS, Yong SK, Li H, ALOthman ZA, Wilson LD, et al.
    Int J Biol Macromol, 2023 Aug 30;247:125806.
    PMID: 37453635 DOI: 10.1016/j.ijbiomac.2023.125806
    An effective hydrothermally prepared chitosan-benzaldehyde/SiO2 adsorbent (CTA-BZA/SiO2) employed functionalization of a CTA biopolymer with SiO2 nanoparticles and BZA. CTA-BZA/SiO2 is an adsorbent that was utilized for the adsorption of an acidic dye (acid red 88, AR88) from synthetic wastewater. The fundamental adsorption variables (A: CTA-BZA/SiO2 dosage (0.02-0.1 g); B: pH (4-10); and C: duration (10-60)) were optimized via the Box-Behnken design (BBD). The Langmuir and Freundlich isotherms (coefficients of determination R2 = 0.99) agreed well with empirical data of AR88 adsorption by CTA-BZA/SiO2. The pseudo-first-order model showed reasonable agreement with the kinetic data of AR88 adsorption by CTA-BZA/SiO2. The maximal AR88 adsorption capacity (qmax) for CTA-BZA/SiO2 was identified to be 252.4 mg/g. The electrostatic attractions between both the positively charged CTA-BZA/SiO2 adsorbent and the AR88 anions, plus the n-π, π-π, and H-bond interactions contribute to the favourable adsorption process. This study reveals that CTA-BZA/SiO2 has the capacity to be a suitable adsorbent for the removal of a wider range of organic dyes from industrial effluents.
  2. Abdulhameed AS, Hapiz A, Musa SA, Kashi E, Wu R, ALOthman ZA, et al.
    Int J Biol Macromol, 2024 Jan;256(Pt 2):128463.
    PMID: 38029908 DOI: 10.1016/j.ijbiomac.2023.128463
    In this study, a new biocomposite magnetic adsorbent (magnetic glyoxal-chitosan Schiff base/organically modified montmorillonite (MCTS-GOX/OMMT)) was synthesized and employed for the adsorption of reactive blue 19 dye (RB19) from aqueous environment. The physicochemical properties of the MCTS-GOX/OMMT were confirmed by using various characterization techniques such as BET, XRD, FTIR, SEM-EDX, VSM, and pHpzc. The adsorption key variables were statistically optimized via Box-Behnken design (BBD) And accordingly the best operational conditions to achieve maximum RB19 removal were recorded at MCTS-GOX/OMMT dosage = 0.1 g/0.1 L, solution pH = 4, and working temperature = 25 °C. The adsorption process for RB19 appeared to follow the pseudo-second-order kinetic and the Langmuir isotherm models, according to the findings of the adsorption kinetics and equilibrium investigations. The maximum adsorption capacity of the MCTS-GOX/OMMT towards RB19 was 122.3 mg/g, demonstrating its preferable adsorption capability. The successful development of this novel magnetic bioadsorbent with excellent adsorption ability towards organic dyes and efficient separation ability opens possibilities for its practical application in wastewater treatment and dye removal processes.
  3. Abdulhameed AS, Wu R, Musa SA, Agha HM, ALOthman ZA, Jawad AH, et al.
    Int J Biol Macromol, 2024 Jan;256(Pt 1):128267.
    PMID: 37992917 DOI: 10.1016/j.ijbiomac.2023.128267
    In this study, chitosan/nano SiO2 (CTS/NS) was chemically modified with bisphenol A diglycidyl ether (BADGE) cross-linker-assisted hydrothermal process to create an effective adsorbent, CTS-BADGE/NS, for the removal of reactive orange 16 (RO16) dye from aquatic systems. Box-Behnken design (BBD) was used to optimize the adsorption process by varying the adsorbent dose (0.02-0.1 g/100 mL), pH (4-10), and time (20-360 min). The adsorption isotherm results indicated that the Langmuir model fits the experimental data well, suggesting that the adsorption process involves a monolayer formation of RO16 on the surface of CTS-BADGE/NS. The kinetic modeling of RO16 adsorption by CTS-BADGE/NS demonstrated that the pseudo-first-order model fits the adsorption data. CTS-BADGE/NS achieved an adsorption capacity of 97.8 mg/g for RO16 dye at optimum desirability functions of dosage 0.099 g/100 mL, solution pH of 4.44, and temperature of 25 °C. Overall, the π-π electron donor-acceptor system significantly improved the adsorption performance of the CTS-BADGE/NS. The results of the regeneration investigation demonstrate that the CTS-BADGE/NS exhibits effective adsorption of RO16, even after undergoing five consecutive cycles. The results of this study suggest that the developed CTS-BADGE/NS composite can be a promising adsorbent for water purification applications.
  4. Zhan Y, Wen Y, Zheng F, Du LJ, Chen TY, Shen XL, et al.
    Mol Neurobiol, 2024 Mar;61(3):1543-1561.
    PMID: 37728849 DOI: 10.1007/s12035-023-03600-8
    Enteric glial cells (EGCs) are the major component of the enteric nervous system and affect the pathophysiological process of intestinal motility dysfunction. MicroRNAs (miRNAs) play an important role in regulating gastrointestinal homeostasis. However, the mechanism of miRNA-mediated regulation of EGCs in intestinal dysmotility remains unclear. In this study, we investigated the effect of EGC apoptosis on intestinal dysmotility, and the effect of miR-26b-3p on EGC proliferation and apoptosis in vivo and in vitro. A loperamide hydrochloride (Lop)-induced constipated mouse model and an in vitro culture system of rat EGCs were established. The transcriptome was used to predict the differentially expressed gene miR-26b-3p and the target gene Frizzled 10 (FZD10), and their targeting binding relationship was verified by luciferase. EGCs were transfected with miR-26b-3p mimic or antagomir, and the FZD10 expression was down-regulated by siRNA. Immunofluorescence and flow cytometry were used to detect EGC apoptosis. MiR-26b-3p and FZD10 expressions were examined using quantitative real-time PCR (qRT-PCR). The CCK-8 assay was used to detect EGC proliferation. The protein levels were detected by Western blotting and enzyme-linked immunosorbent assay (ELISA). The results showed that miR-26b-3p was up-regulated in the Lop group, whereas FZD10 was down-regulated, and EGC apoptosis was increased in the colon of intestinal dysmotility mice. FZD10 down-regulation and miR-26b-3p mimic significantly increased glycogen synthase kinase-3β phosphorylation (p-GSK3β) levels, decreased β-catenin expression, and promoted EGC apoptosis. MiR-26b-3p antagomir alleviated intestinal dysmotility, promoted EGC increased activity of EGCs, and reduced EGC apoptosis in vivo. In conclusion, this study indicated that miR-26b-3p promotes intestinal motility disorders by targeting FZD10 to block GSK3β/β-catenin signaling and induces apoptosis in EGCs. Our results provide a new research target for the treatment and intervention of intestinal dysmotility.
  5. Zheng Y, Lamoureux E, Finkelstein E, Wu R, Lavanya R, Chua D, et al.
    Invest Ophthalmol Vis Sci, 2011;52(12):8799-805.
    PMID: 21969296 DOI: 10.1167/iovs.11-7700
    It is known that a person's socioeconomic status (SES; individual-level SES) is closely correlated with his or her degree of visual impairment. Whether there is an independent relationship between area-level measures of SES (e.g., living in a lower SES environment) and visual impairment is unclear. This study describes the associations of area-level SES with visual impairment.
  6. Jiang X, Li Y, Feng JL, Nik Nabil WN, Wu R, Lu Y, et al.
    Front Cell Dev Biol, 2020;8:598620.
    PMID: 33392189 DOI: 10.3389/fcell.2020.598620
    The re-proliferation of quiescent cancer cells is considered to be the primary contributor to prostate cancer (Pca) recurrence and progression. In this study, we investigated the inhibitory effect of safranal, a monoterpene aldehyde isolated from Crocus sativus (saffron), on the re-proliferation of quiescent Pca cells in vitro and in vivo. The results showed that safranal efficiently blocked the re-activation of quiescent Pca cells by downregulating the G0/G1 cell cycle regulatory proteins CDK2, CDK4, CDK6, and phospho-Rb at Ser807/811 and elevating the levels of cyclin-dependent kinase inhibitors, p21 and p27. Further investigation on the underlying mechanisms revealed that safranal suppressed the mRNA and protein expression levels of Skp2, possibly through the deregulation of the transcriptional activity of two major transcriptional factors, E2F1 and NF-κB subunits. Moreover, safranal inhibited AKT phosphorylation at Ser473 and deregulated both canonical and non-canonical NF-κB signaling pathways. Safranal suppressed the tumor growth of quiescent Pca cell xenografts in vivo. Furthermore, safranal-treated tumor tissues exhibited a reduction in Skp2, E2F1, NF-κB p65, p-IκBα (Ser32), c-MYC, p-Rb (Ser807), CDK4, CDK6, and CDK2 and an elevation of p27 and p21 protein levels. Therefore, our findings demonstrate that safranal suppresses cell cycle re-entry of quiescent Pca cells in vitro and in vivo plausibly by repressing the transcriptional activity of two major transcriptional activators of Skp2, namely, E2F1 and NF-κB, through the downregulation of AKT phosphorylation and NF-κB signaling pathways, respectively.
  7. Wu R, Zou P, Tan G, Hu Z, Wang Y, Ning Z, et al.
    Ecol Evol, 2019 May;9(10):5766-5776.
    PMID: 31160997 DOI: 10.1002/ece3.5160
    Hybridization is very common in flowering plants and it plays a significant role in plant evolution and adaptation. Melastoma L. (Melastomataceae) comprises about 80-90 species in tropical Asia and Oceania, among which 41 species occur in Borneo. Natural hybridization is frequently reported in Melastoma in China, but so far there have been no confirmed cases of hybridization in Southeast Asia (including Borneo), where most species occur. Here, we identified a case of natural hybridization between Melastoma malabathricum L. and Melastoma beccarianum Cogn. in Sarawak, Malaysia, by using sequence data of three nuclear genes and one chloroplast intergenic spacer. Melastoma malabathricum is the most widespread species of this genus, occurring in almost the whole range of this genus, while M. beccarianum is a local species endemic to northern Borneo. Our results showed that natural hybridization and introgression occur between M. malabathricum and M. beccarianum, and the introgression was asymmetrical, mainly from M. malabathricum to M. beccarianum. As adaptive traits can be transferred by introgression, our study suggests that natural hybridization should be a significant mechanism for the evolution and adaptation of Melastoma in Southeast Asia. However, introgression from the common species M. malabathricum to the relatively rare species M. beccarianum may cause the decline of M. beccarianum, incurring conservation concern. With a large number of species of Melastoma and almost year-around flowering in Southeast Asia, more cases of natural hybridization are expected to be found and identified in near future.
  8. Wu R, Abdulhameed AS, Jawad AH, Yong SK, Li H, ALOthman ZA, et al.
    Int J Biol Macromol, 2023 Dec 01;252:126342.
    PMID: 37591432 DOI: 10.1016/j.ijbiomac.2023.126342
    Herein, the polymer nanomatrix of chitosan/SiO2 (CHI/n-SiO2) was enriched with a π-π electron donor-acceptor system using diaromatic rings of benzil (BEZ) assisted via a hydrothermal process to obtain an effective adsorbent of chitosan-benzil/SiO2 (CHI-BEZ/n-SiO2). The polymer nanomatrix (CHI/n-SiO2) and the resulting adsorbent (CHI-BEZ/n-SiO2) were applied to remove the anionic acid red 88 (AR88) dye from aqueous media in a comparative mode. Box-Behnken design (BBD) was adopted to optimize AR88 adsorption onto CHI/n-SiO2 and CHI-BEZ/n-SiO2 with respect to variables that influence AR88 adsorption (adsorbent dose: 0.02-0.1 g/100 mL; pH: 4-10; and time: 10-90). The adsorption studies at equilibrium were conducted with a variety of initial AR88 dye concentrations (20-200 mg/L). The adsorption isotherm results reveal that the AR88 adsorption by CHI/n-SiO2 and CHI-BEZ/n-SiO2 are described by the Langmuir model. The kinetic adsorption profiles of AR88 with CHI/n-SiO2 and CHI-BEZ/n-SiO2 reveal that the pseudo-first-order model provides the best fit results. Interestingly, CHI-BEZ/n-SiO2 has a high adsorption capacity (261.2 mg/g), which exceeds the adsorption capacity of CHI/n-SiO2 (215.1 mg/g) that relates to the surface effects of SiO2 and the functionalization of chitosan with BEZ. These findings show that CHI-BEZ/n-SiO2 represents a highly efficient adsorbent for the removal of harmful pollutants from water, which outperforming the CHI/n-SiO2 system.
  9. Huang Y, Li Y, Wu M, Wang HQ, Yuan X, Gholam T, et al.
    J Synchrotron Radiat, 2020 Jan 01;27(Pt 1):83-89.
    PMID: 31868740 DOI: 10.1107/S160057751901381X
    Surface polarity with different crystal orientations has been demonstrated as a crucial parameter in determining the physical properties and device applications in many transition metal oxide and semiconductor compound systems. The influences of surface polarity on electronic structures in nitrogen-incorporated ZnO lattices have been investigated in the present work. The successful doping of nitrogen atoms in ZnO lattices is suggested by the existence of N-related chemical bonds obtained from X-ray photoelectron spectroscopy analysis where a pronounced N-Zn peak intensity has been observed in the (000\bar 1)-terminated polar ZnO compound compared with the (10\bar 10)-terminated nonpolar ZnO compound. An energy shift of the valence band maximum towards the Fermi level has been resolved for both polar and nonpolar ZnO lattices, whereas a charge redistribution of the O 2p hybridized states is only resolved for o-plane ZnO with a polar surface. Angular-dependent X-ray absorption analyses at the O K-edge reveal enhanced surface-state contributions and asymmetric O 2p orbital occupations in the (000\bar 1)-terminated o-plane ZnO compound. The results shed light on the efficient nitrogen doping in ZnO lattices with polar surfaces. The comprehensive electronic structure investigations of correlations between impurity doping and surface polarity in ZnO lattices may also offer guidance for the material design in other transition metal oxide and semiconductor systems.
  10. Young G, Srivastava A, Kavakli K, Ross C, Sathar J, You CW, et al.
    Lancet, 2023 Mar 29.
    PMID: 37003287 DOI: 10.1016/S0140-6736(23)00284-2
    BACKGROUND: Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance haemostasis in people with haemophilia A or haemophilia B, irrespective of inhibitor status. We evaluated the efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors.

    METHODS: This multicentre, randomised, open-label phase 3 study was done at 26 sites (primarily secondary or tertiary centres) in 12 countries. Men, boys, and young adults aged 12 years or older with severe haemophilia A or haemophilia B with inhibitors previously treated with on-demand bypassing agents were randomly assigned (2:1) to receive once-a-month 80 mg subcutaneous fitusiran prophylaxis (fitusiran prophylaxis group) or to continue with bypassing agents on-demand (bypassing agents on-demand group) for 9 months. The primary endpoint was mean annualised bleeding rate during the efficacy period in the intention-to-treat population estimated by negative binomial model. Safety was assessed as a secondary endpoint in the safety population. This trial is complete and is registered with ClinicalTrials.gov, NCT03417102.

    FINDINGS: Between Feb 14, 2018, and June 23, 2021, 85 participants were screened for inclusion, of whom 57 (67%; 57 [100%] men; median age 27·0 years [IQR 19·5-33·5]) were randomly assigned: 19 (33%) participants to the bypassing agent on-demand group and 38 (67%) participants to the fitusiran prophylaxis. Negative binomial model-based mean annualised bleeding rate was significantly lower in the fitusiran prophylaxis group (1·7 [95% CI 1·0-2·7]) than in the bypassing agents on-demand group (18·1 [10·6-30·8]), corresponding to a 90·8% (95% CI 80·8-95·6) reduction in annualised bleeding rate in favour of fitusiran prophylaxis (p<0·0001). 25 (66%) participants had zero treated bleeds in the fitusiran prophylaxis group versus one (5%) in the bypassing agents on-demand group. The most frequent treatment-emergent adverse event in the fitusiran prophylaxis group was increased alanine aminotransferase in 13 (32%) of 41 participants in the safety population; there were no increased alanine aminotransferase treatment-emergent adverse events in the bypassing agents on-demand group. Suspected or confirmed thromboembolic events were reported in two (5%) participants in the fitusiran prophylaxis group. No deaths were reported.

    INTERPRETATION: Subcutaneous fitusiran prophylaxis resulted in statistically significant reductions in annualised bleeding rate in participants with haemophilia A or haemophilia B with inhibitors, with two-thirds of participants having zero bleeds. Fitusiran prophylaxis might show haemostatic efficacy in participants with haemophilia A or haemophilia B with inhibitors; therefore, the therapeutic might have the potential to improve the management of people with haemophilia.

    FUNDING: Sanofi.

  11. Wu R, Xi Z, Liu M, Ren H, Dai R, Jiang X, et al.
    Chin Med, 2023 May 28;18(1):61.
    PMID: 37246229 DOI: 10.1186/s13020-023-00774-0
    BACKGROUND: Pancreatic cancer (PAC), a malignancy that is fatal and commonly diagnosed at a late stage. Despite considerable advancements in cancer treatment, the survival rate of PAC remains largely consistent for the past 60 years. The traditional Chinese medicine formula Pulsatilla Decoction (PD) has been clinically used to treat inflammatory diseases for millennia and recently as a supplementary anti-cancer treatment in China. However, the bioactive ingredients and mechanisms underlying its anti-cancer effect remains unclear.

    METHODS: The composition and quality control of PD were verified through analysis by high performance liquid chromatography. Cell viability was determined using Cell Counting Kit-8 assay. The cell cycle distribution was analyzed through PI staining and flow cytometry analysis, while apoptotic cells were measured by double staining with Annexin V-FITC and PI. We used immunoblotting to examine protein expressions. The in vivo effects of β-peltatin and podophyllotoxin were evaluated on a subcutaneously-xenografted BxPC-3 cell nude mice model.

    RESULTS: The current study demonstrated that PD markedly inhibited PAC cell proliferation and triggered their apoptosis. Four herbal PD formula was then disassembled into 15 combinations of herbal ingredients and a cytotoxicity assay showed that the Pulsatillae chinensis exerted the predominant anti-PAC effect. Further investigation indicated that β-peltatin was potently cytotoxic with IC50 of ~ 2 nM. β-peltatin initially arrested PAC cells at G2/M phase, followed by apoptosis induction. Animal study confirmed that β-peltatin significantly suppressed the growth of subcutaneously-implanted BxPC-3 cell xenografts. Importantly, compared to podophyllotoxin that is the parental isomer of β-peltatin but clinically obsoleted due to its severe toxicity, β-peltatin exhibited stronger anti-PAC effect and lower toxicity in mice.

    CONCLUSIONS: Our results demonstrate that Pulsatillae chinensis and particularly its bioactive ingredient β-peltatin suppress PAC by triggering cell cycle arrest at G2/M phase and apoptosis.

  12. Vithana EN, Aung T, Khor CC, Cornes BK, Tay WT, Sim X, et al.
    Hum Mol Genet, 2011 Feb 15;20(4):649-58.
    PMID: 21098505 DOI: 10.1093/hmg/ddq511
    Central corneal thickness (CCT) is a risk factor of glaucoma, the most common cause of irreversible blindness worldwide. The identification of genetic determinants affecting CCT in the normal population will provide insights into the mechanisms underlying the association between CCT and glaucoma, as well as the pathogenesis of glaucoma itself. We conducted two genome-wide association studies for CCT in 5080 individuals drawn from two ethnic populations in Singapore (2538 Indian and 2542 Malays) and identified novel genetic loci significantly associated with CCT (COL8A2 rs96067, p(meta) = 5.40 × 10⁻¹³, interval of RXRA-COL5A1 rs1536478, p(meta) = 3.05 × 10⁻⁹). We confirmed the involvement of a previously reported gene for CCT and brittle cornea syndrome (ZNF469) [rs9938149 (p(meta) = 1.63 × 10⁻¹⁶) and rs12447690 (p(meta) = 1.92 × 10⁻¹⁴)]. Evidence of association exceeding the formal threshold for genome-wide significance was observed at rs7044529, an SNP located within COL5A1 when data from this study (n = 5080, P = 0.0012) were considered together with all published data (reflecting an additional 7349 individuals, p(Fisher) = 1.5 × 10⁻⁹). These findings implicate the involvement of collagen genes influencing CCT and thus, possibly the pathogenesis of glaucoma.
  13. Khor CC, Do T, Jia H, Nakano M, George R, Abu-Amero K, et al.
    Nat Genet, 2016 May;48(5):556-62.
    PMID: 27064256 DOI: 10.1038/ng.3540
    Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.
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