Browse publications by year: 2023

  1. David P, Lescure J, Savage JM, DAS I, Pauwels OSG, Vogel G, et al.
    Zootaxa, 2023 Jan 31;5231(3):331-339.
    PMID: 37045142 DOI: 10.11646/zootaxa.5231.3.8
    The purpose of this paper is to solve an overlooked nomenclatural problem involving two taxa of Colubridae, both described as Coluber korros. The first one is Coluber korros Schlegel, 1837, now Ptyas korros, a well-known and widespread species in south-east Asia. Its senior homonym is Coluber korros Lesson, 1831, a long forgotten taxon. Furthermore, these taxa are undoubtedly non-conspecific. We tentatively identify the holotype of this latter taxon as a large specimen of Coelognathus radiatus (F. Boie, 1827) and we specify its type locality as "Region of Kolkata, West Bengal State, eastern India" (the same specification of type-locality can hence be applied to the elapid Naja kaouthia Lesson, 1831). Nevertheless, following the strict principle of priority, Coluber korros Lesson, 1831 has priority over Coluber korros Schlegel, 1837. Based on the Code, we use Article 23.9 on reversal of precedence in order to preserve the use of the well-known taxon Coluber korros Schlegel, 1837 (now Ptyas korros) against its senior primary homonym Coluber korros Lesson, 1831. Finally, we consider Coluber boncorage Lesson, 1831 to be a nomen dubium.
    MeSH terms: Animals; Lizards*; Colubridae*; Elapidae
  2. Yu K, Wang C, Maddison WP, Zhang J
    Zootaxa, 2023 Jan 31;5231(3):201-248.
    PMID: 37045149 DOI: 10.11646/zootaxa.5231.3.1
    Two new genera of euophryine jumping spiders in the Laufeia group are established for species from Southeast Asia: Amoenema Yu & Zhang, gen. nov. and Lokina Yu, Maddison & Zhang, gen. nov., with descriptions of 12 new species: Amoenema erhai Yu & Zhang, sp. nov. (♂♀, type species), A. liuae Yu & Zhang, sp. nov. (♂♀), A. zizhongi Yu & Zhang, sp. nov. (♂♀), Lokina blombergi Yu, Maddison & Zhang, sp. nov. (♂♀), L. chiyou Yu & Zhang, sp. nov. (♂♀, type species), L. fuxi Yu & Zhang, sp. nov. (♂♀), L. kubah Yu, Maddison & Zhang, sp. nov. (♂), L. nyuewa Yu & Zhang, sp. nov. (♂♀), L. pixi Yu, Maddison & Zhang, sp. nov. (♂), L. tamasi Yu & Zhang, sp. nov. (♂♀), L. wuyi Yu & Zhang, sp. nov. (♂), L. zhishengi Yu & Zhang, sp. nov. (♂). In addition, three new combinations are proposed: Amoenema robusta (Lei & Peng, 2012) comb. nov. (transferred from Euophrys C. L. Koch, 1834), Lokina eximia (Zhang & Maddison, 2012) comb. nov. (transferred from Laufeia Simon, 1889) and L. tengchongensis (Lei & Peng, 2012) comb. nov. (transferred from Chalcovietnamicus Marusik, 1991).
    MeSH terms: Animals; China; Malaysia; Spiders*
  3. Park KT, Heppner JB
    Zootaxa, 2023 Mar 22;5256(5):434-456.
    PMID: 37045213 DOI: 10.11646/zootaxa.5256.5.2
    Sumatra is the second largest island that is fully within Indonesian territory, but it is one of the most poorly explored areas for species diversity of the family Lecithoceridae, with less than 10 known species. In the present paper, six new species of Thubana Walker, 1864 (T. sumatrana sp. nov., T. spiniosa sp. nov., T. lata sp. nov., T. prapatensis sp. nov., T. siantarensis sp. nov., and T. selenisa sp. nov.) and three new species of Torodora Meyrick (T. diehliella sp. nov., T. exilivalvata sp. nov., and T. squariella sp. nov.) are described from Sumatra. In addition, Thubana ochracea Park & Abang, 2005, which was described from Sarawak, Malaysia, is reported for the first time from Sumatra. Illustrations of adults and genitalia of all new species are given. A list of the known species of the subfamily Torodorinae from Indonesia is provided.
    MeSH terms: Animals; Genitalia; Indonesia; Lepidoptera*; Moths*; Animal Distribution
  4. Tanveer S, Schluter PJ, Porter RJ, Boden J, Beaglehole B, Sulaiman-Hill R, et al.
    BMJ Open, 2023 Apr 12;13(4):e067886.
    PMID: 37045574 DOI: 10.1136/bmjopen-2022-067886
    INTRODUCTION: The COVID-19 pandemic exposed people to significant and prolonged stress. The psychosocial impacts of the pandemic have been well recognised and reported in high-income countries (HICs) but it is important to understand the unique challenges posed by COVID-19 in low- and middle-income countries (LMICs) where limited international comparisons have been undertaken. This protocol was therefore devised to study the psychosocial impacts of the COVID-19 pandemic in seven LMICs using scales that had been designed for or translated for this purpose.

    METHODS AND ANALYSIS: This cross-sectional study uses an online survey to administer a novel COVID Psychosocial Impacts Scale (CPIS) alongside established measures of psychological distress, post-traumatic stress, well-being and post-traumatic growth in the appropriate language. Participants will include adults aged 18 years and above, recruited from Indonesia, Iraq, Iran, Malaysia, Pakistan, Somalia and Turkey, with a pragmatic target sample size of 500 in each country.Data will be analysed descriptively on sociodemographic and study variables. In addition, CPIS will be analysed psychometrically (for reliability and validity) to assess the suitability of use in a given context. Finally, within-subjects and between-subjects analyses will be carried out using multi-level mixed-effect models to examine associations between key sociodemographic and study variables.

    ETHICS AND DISSEMINATION: Ethical approval was granted by the Human Ethics Committee, University of Otago, New Zealand (Ref. No. 21/102). In addition, international collaborators obtained local authorisation or ethical approval in their respective host universities before data collection commenced.Participants will give informed consent before taking part. Data will be collected and stored securely on the University of Otago, New Zealand Qualtrics platform using an auto-generated non-identifiable letter-number string. Data will be available on reasonable request. Findings will be disseminated by publications in scientific journals and/or conference presentations.

    TRIAL REGISTRATION NUMBER: NCT05052333.

    MeSH terms: Adult; Cross-Sectional Studies; Humans; Surveys and Questionnaires; Reproducibility of Results; Pandemics
  5. Abbasi M, Gholizadeh R, Kasaee SR, Vaez A, Chelliapan S, Fadhil Al-Qaim F, et al.
    Sci Rep, 2023 Apr 12;13(1):5987.
    PMID: 37046068 DOI: 10.1038/s41598-023-33095-1
    In recent years, mesoporous silica nanoparticles (MSNs) have been applied in various biomedicine fields like bioimaging, drug delivery, and antibacterial alternatives. MSNs could be manufactured through green synthetic methods as environmentally friendly and sustainable synthesis approaches, to improve physiochemical characteristics for biomedical applications. In the present research, we used Rutin (Ru) extract, a biocompatible flavonoid, as the reducing agent and nonsurfactant template for the green synthesis of Ag-decorated MSNs. Transmission electron microscopy (TEM), zeta-potential, x-ray powder diffraction (XRD), fourier transform infrared (FTIR) spectroscopy analysis, scanning electron microscopy (SEM), brunauer-emmett-teller (BET) analysis, and energy-dispersive system (EDS) spectroscopy were used to evaluate the Ag-decorated MSNs physical characteristics. The antimicrobial properties were evaluated against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and also different types of candida. The cytotoxicity test was performed by using the MTT assay. Based on the findings, the significant antimicrobial efficacy of Ru-Ag-decorated MSNs against both gram positive and gram negative bacteria and different types of fungi was detected as well as acceptable safety and low cytotoxicity even at lower concentrations. Our results have given a straightforward and cost-effective method for fabricating biodegradable Ag-decorated MSNs. The applications of these MSNs in the domains of biomedicine appear to be promising.
    MeSH terms: Anti-Bacterial Agents/chemistry; Escherichia coli; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Rutin/pharmacology; Silicon Dioxide/chemistry; Staphylococcus aureus
  6. Kuan XY, Fauzi NSA, Ng KY, Bakhtiar A
    Mol Neurobiol, 2023 Aug;60(8):4169-4183.
    PMID: 37046137 DOI: 10.1007/s12035-023-03337-4
    Telomeres, also known as the "protective caps" of our chromosomes, shorten with each cell cycle due to the end replication problem. This process, termed telomere attrition, is associated with many age-related disorders, such as Alzheimer's disease (AD). Despite the numerous studies conducted in this field, the role of telomere attrition in the onset of the disease remains unclear. To investigate the causal relationship between short telomeres and AD, this review aims to highlight the primary factors that regulate telomere length and maintain its integrity, with an additional outlook on the role of oxidative stress, which is commonly associated with aging and molecular damage. Although some findings thus far might be contradictory, telomere attrition likely plays a crucial role in the progression of AD due to its close association with oxidative stress. The currently available treatments for AD are only symptomatic without affecting the progression of the disease. The components of telomere biology discussed in this paper have previously been studied as an alternative treatment option for several diseases and have exhibited promising in vitro and in vivo results. Hence, this should provide a basis for future research to develop a potential therapeutic strategy for AD. (Created with BioRender.com).
    MeSH terms: Aging/genetics; Biology; Humans; Telomere/genetics; Telomere/metabolism; Telomere Shortening
  7. Mekzali NW, Chee CW, Abdullah I, Lee YK, Rashid NN, Lee VS, et al.
    Med Chem, 2023;19(9):897-905.
    PMID: 37046198 DOI: 10.2174/1573406419666230410134213
    BACKGROUND: KRAS and p53 are two of the most common genetic alterations associated with colorectal cancer. New drug development targeting these mutated genes in colorectal cancer may serve as a potential treatment avenue to the current regimen.

    OBJECTIVE: The objective of the present study was to investigate the effects of alkoxy chain length and 1-hydroxy group on anticolorectal cancer activity of a series of 2-bromoalkoxyanthraquinones and corroborate it with their in silico properties.

    METHODS: In vitro anticancer activity of 2-bromoalkoxyanthraquinones was evaluated against HCT116, HT29, and CCD841 CoN cell lines, respectively. Molecular docking was performed to understand the interactions of these compounds with putative p53 and KRAS targets (7B4N and 6P0Z).

    RESULTS: 2-Bromoalkoxyanthraquinones with the 1-hydroxy group were proven to be more active than the corresponding counterparts in anticancer activity. Among the tested compounds, compound 6b with a C3 alkoxy chain exhibited the most promising antiproliferation activity against HCT116 cells (IC50 = 3.83 ± 0.05 μM) and showed high selectivity for HCT116 over CCD841 CoN cells (SI = 45.47). The molecular docking reveals additional hydrogen bonds between the 1-hydroxy group of 6b and the proteins. Compound 6b has adequate lipophilicity (cLogP = 3.27) and ligand efficiency metrics (LE = 0.34; LLE = 2.15) close to the proposed acceptable range for an initial hit.

    CONCLUSION: This work highlights the potential of the 1-hydroxy group and short alkoxy chain on anticolorectal cancer activity of 2-bromoalkoxyanthraquinones. Further optimisation may be warranted for compound 6b as a therapeutic agent against colorectal cancer.

    MeSH terms: Drug Screening Assays, Antitumor; Humans; Structure-Activity Relationship; Molecular Structure; Tumor Suppressor Protein p53/metabolism; Tumor Suppressor Protein p53/pharmacology; Proto-Oncogene Proteins p21(ras)/metabolism; Proto-Oncogene Proteins p21(ras)/pharmacology; HCT116 Cells; Cell Line, Tumor; Cell Proliferation; Molecular Docking Simulation
  8. Hassan MRA, Chan HK, Nordin M, Yahya R, Sulaiman WRW, Merican SAA, et al.
    Harm Reduct J, 2023 Apr 12;20(1):48.
    PMID: 37046294 DOI: 10.1186/s12954-023-00780-3
    BACKGROUND: Despite advancements in hepatitis C virus (HCV) treatment, low uptake among hard-to-reach populations remains a global issue. The current study aimed to assess the feasibility of a modified same-day test-and-treat model in improving HCV care for people who inject drugs (PWID) living in resource-constrained rural areas.

    METHODS: A pilot study was conducted in four primary healthcare (PHC) centers in Malaysia. The model's key features included on-site HCV ribonucleic acid (RNA) testing using a shared GeneXpert® system; noninvasive biomarkers for cirrhosis diagnosis; and extended care to PWID referred from nearby PHC centers and outreach programs. The feasibility assessment focused on three aspects of the model: demand (i.e., uptake of HCV RNA testing and treatment), implementation (i.e., achievement of each step in the HCV care cascade), and practicality (i.e., ability to identify PWID with HCV and expedite treatment initiation despite resource constraints).

    RESULTS: A total of 199 anti-HCV-positive PWID were recruited. They demonstrated high demand for HCV care, with a 100% uptake of HCV RNA testing and 97.4% uptake of direct-acting antiviral treatment. The rates of HCV RNA positivity (78.4%) and sustained virologic response (92.2%) were comparable to standard practice, indicating the successful implementation of the model. The model was also practical, as it covered non-opioid-substitution-therapy-receiving individuals and enabled same-day treatment in 71.1% of the participants.

    CONCLUSIONS: The modified same-day test-and-treat model is feasible in improving HCV care for rural PWID. The study finding suggests its potential for wider adoption in HCV care for hard-to-reach populations.

    MeSH terms: Antiviral Agents/therapeutic use; Feasibility Studies; Humans; Pilot Projects; RNA/therapeutic use; Hepacivirus/genetics; Drug Users*
  9. Albarrak J, Al-Shamsi H
    Cancers (Basel), 2023 Mar 28;15(7).
    PMID: 37046662 DOI: 10.3390/cancers15072001
    The burden of hepatocellular carcinoma (HCC) is on the rise in the Gulf region, with most patients being diagnosed in the intermediate or advanced stages. Surgery is a treatment option for only a few, and the majority of patients receive either locoregional treatment (percutaneous ethanol injection, radiofrequency ablation, transarterial chemoembolization [TACE], radioembolization, radiotherapy, or transarterial radioembolization) or systemic therapy (for those ineligible for locoregional treatments or who do not benefit from TACE). The recent emergence of novel immunotherapies such as immune checkpoint inhibitors has begun to change the landscape of systemic HCC treatment in the Gulf. The combination of atezolizumab and bevacizumab is currently the preferred first-line therapy in patients not at risk of bleeding. Additionally, the HIMALAYA trial has demonstrated the superiority of the durvalumab plus tremelimumab combination (STRIDE regimen) therapy in efficacy and safety compared with sorafenib in patients with unresectable HCC. However, there is a lack of data on post-progression treatment after first-line therapy with either atezolizumab plus bevacizumab or durvalumab plus tremelimumab regimens, highlighting the need for better-designed studies for improved management of patients with unresectable HCC in the Gulf region.
  10. Nik Ab Kadir MN, Mohd Hairon S, Ab Hadi IS, Yusof SN, Muhamat SM, Yaacob NM
    Cancers (Basel), 2023 Mar 30;15(7).
    PMID: 37046725 DOI: 10.3390/cancers15072064
    The PREDICT breast cancer is a well-known online calculator to estimate survival probability. We developed a new prognostic model, myBeST, due to the PREDICT tool's limitations when applied to our patients. This study aims to compare the performance of the two models for women with breast cancer in Malaysia. A total of 532 stage I to III patient records who underwent surgical treatment were analysed. They were diagnosed between 2012 and 2016 in seven centres. We obtained baseline predictors and survival outcomes by reviewing patients' medical records. We compare PREDICT and myBeST tools' discriminant performance using receiver-operating characteristic (ROC) analysis. The five-year observed survival was 80.3% (95% CI: 77.0, 83.7). For this cohort, the median five-year survival probabilities estimated by PREDICT and myBeST were 85.8% and 82.6%, respectively. The area under the ROC curve for five-year survival by myBeST was 0.78 (95% CI: 0.73, 0.82) and for PREDICT was 0.75 (95% CI: 0.70, 0.80). Both tools show good performance, with myBeST marginally outperforms PREDICT discriminant performance. Thus, the new prognostic model is perhaps more suitable for women with breast cancer in Malaysia.
  11. Mat Lazim N, Yousaf A, Abusalah MAH, Sulong S, Mohd Ismail ZI, Mohamud R, et al.
    Cancers (Basel), 2023 Mar 31;15(7).
    PMID: 37046772 DOI: 10.3390/cancers15072111
    Salivary gland carcinomas (SGCs) are a diverse collection of malignant tumors with marked differences in biological activity, clinical presentation and microscopic appearance. Although the etiology is varied, secondary radiation, oncogenic viruses as well as chromosomal rearrangements have all been linked to the formation of SGCs. Epigenetic modifications may also contribute to the genesis and progression of SGCs. Epigenetic modifications are any heritable changes in gene expression that are not caused by changes in DNA sequence. It is now widely accepted that epigenetics plays an important role in SGCs development. A basic epigenetic process that has been linked to a variety of pathological as well as physiological conditions including cancer formation, is DNA methylation. Transcriptional repression is caused by CpG islands hypermethylation at gene promoters, whereas hypomethylation causes overexpression of a gene. Epigenetic changes in SGCs have been identified, and they have been linked to the genesis, progression as well as prognosis of these neoplasms. Thus, we conduct a thorough evaluation of the currently known evidence on the involvement of epigenetic processes in SGCs.
  12. Morshed AKMH, Paul S, Hossain A, Basak T, Hossain MS, Hasan MM, et al.
    Cancers (Basel), 2023 Apr 03;15(7).
    PMID: 37046789 DOI: 10.3390/cancers15072128
    Despite significant therapeutic advancements for cancer, an atrocious global burden (for example, health and economic) and radio- and chemo-resistance limit their effectiveness and result in unfavorable health consequences. Natural compounds are generally considered safer than synthetic drugs, and their use in cancer treatment alone, or in combination with conventional therapies, is increasingly becoming accepted. Interesting outcomes from pre-clinical trials using Baicalein in combination with conventional medicines have been reported, and some of them have also undergone clinical trials in later stages. As a result, we investigated the prospects of Baicalein, a naturally occurring substance extracted from the stems of Scutellaria baicalensis Georgi and Oroxylum indicum Kurz, which targets a wide range of molecular changes that are involved in cancer development. In other words, this review is primarily driven by the findings from studies of Baicalein therapy in several cancer cell populations based on promising pre-clinical research. The modifications of numerous signal transduction mechanisms and transcriptional agents have been highlighted as the major players for Baicalein's anti-malignant properties at the micro level. These include AKT serine/threonine protein kinase B (AKT) as well as PI3K/Akt/mTOR, matrix metalloproteinases-2 & 9 (MMP-2 & 9), Wnt/-catenin, Poly(ADP-ribose) polymerase (PARP), Mitogen-activated protein kinase (MAPK), NF-κB, Caspase-3/8/9, Smad4, Notch 1/Hes, Signal transducer and activator of transcription 3 (STAT3), Nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein-1 (Keap 1), Adenosine monophosphate-activated protein kinase (AMPK), Src/Id1, ROS signaling, miR 183/ezrin, and Sonic hedgehog (Shh) signaling cascades. The promise of Baicalein as an anti-inflammatory to anti-apoptotic/anti-angiogenic/anti-metastatic medicinal element for treating various malignancies and its capability to inhibit malignant stem cells, evidence of synergistic effects, and design of nanomedicine-based drugs are altogether well supported by the data presented in this review study.
  13. Sahrizan NSA, Manan HA, Abdul Hamid H, Abdullah JM, Yahya N
    Cancers (Basel), 2023 Apr 06;15(7).
    PMID: 37046828 DOI: 10.3390/cancers15072168
    Working memory, language and speech abilities, motor skills, and visual abilities are often impaired in children with brain tumours. This is because tumours can invade the brain's functional areas and cause alterations to the neuronal networks. However, it is unclear what the mechanism of tumour invasion is and how various treatments can cause cognitive impairment. Therefore, this study aims to systematically evaluate the effects of tumour invasion on the cognitive, language, motor, and visual abilities of paediatric patients, as well as discuss the alterations and modifications in neuronal networks and anatomy. The electronic database, PubMed, was used to find relevant studies. The studies were systematically reviewed based on the type and location of brain tumours, cognitive assessment, and pre- and post-operative deficits experienced by patients. Sixteen studies were selected based on the inclusion and exclusion criteria following the guidelines from PRISMA. Most studies agree that tumour invasion in the brain causes cognitive dysfunction and alteration in patients. The effects of a tumour on cognition, language, motor, and visual abilities depend on the type of tumour and its location in the brain. The alteration to the neuronal networks is also dependent on the type and location of the tumour. However, the default mode network (DMN) is the most affected network, regardless of the tumour type and location.Furthermore, our findings suggest that different treatment types can also contribute to patients' cognitive function to improve or deteriorate. Deficits that persisted or were acquired after surgery could result from surgical manipulation or the progression of the tumour's growth. Meanwhile, recovery from the deficits indicated that the brain has the ability to recover and reorganise itself.
  14. Mustafa AS, Ali N, Dhillon JS, Sedera D
    Healthcare (Basel), 2023 Apr 06;11(7).
    PMID: 37046978 DOI: 10.3390/healthcare11071051
    Mobile health (mHealth) apps are designed to support health behavior outcomes and improve well-being. The existing body of literature confirms mHealth's overall efficacy in promoting physical activity; however, more research on its utility in sustaining user engagement is needed. Understanding the determinants of an individual's willingness to continue using mHealth is vital to improving the intervention's success. This study developed a unified model and survey instrument adapted from extant literature while introducing new constructs to predict the sustained use of gamified mHealth. A pilot study was conducted to validate the survey instrument using 48 gamified fitness app users in Malaysia. The survey instrument was tested following rigorous guidelines for quantitative research in the information system context. According to the findings, the reliabilities of most measurement items met the criterion, and those items were retained. Overall, this paper contributes by integrating social comparison theory and the self-determination theory for sustaining user engagement with gamified mHealth through an extrinsic and intrinsic motivation perspective.
  15. Simon C, Soga T, Parhar I
    Int J Mol Sci, 2023 Mar 23;24(7).
    PMID: 37047030 DOI: 10.3390/ijms24076056
    The hypothalamic neurohormone kisspeptin-10 (KP-10) was inherently implicated in cholinergic pathologies when aberrant fluctuations of expression patterns and receptor densities were discerned in neurodegenerative micromilieus. That said, despite variable degrees of functional redundancy, KP-10, which is biologically governed by its cognate G-protein-coupled receptor, GPR54, attenuated the progressive demise of α-synuclein (α-syn)-rich cholinergic-like neurons. Under explicitly modeled environments, in silico algorithms further rationalized the surface complementarities between KP-10 and α-syn when KP-10 was unambiguously accommodated in the C-terminal binding pockets of α-syn. Indeed, the neuroprotective relevance of KP-10's binding mechanisms can be insinuated in the amelioration of α-syn-mediated neurotoxicity; yet it is obscure whether these extenuative circumstances are contingent upon prior GPR54 activation. Herein, choline acetyltransferase (ChAT)-positive SH-SY5Y neurons were engineered ad hoc to transiently overexpress human wild-type or E46K mutant α-syn while the mitigation of α-syn-induced neuronal death was ascertained via flow cytometric and immunocytochemical quantification. Recapitulating the specificity observed on cell viability, exogenously administered KP-10 (0.1 µM) substantially suppressed wild-type and E46K mutant α-syn-mediated apoptosis and mitochondrial depolarization in cholinergic differentiated neurons. In particular, co-administrations with a GPR54 antagonist, kisspeptin-234 (KP-234), failed to abrogate the robust neuroprotection elicited by KP-10, thereby signifying a GPR54 dispensable mechanism of action. Consistent with these observations, KP-10 treatment further diminished α-syn and ChAT immunoreactivity in neurons overexpressing wild-type and E46K mutant α-syn. Overall, these findings lend additional credence to the previous notion that KP-10's binding zone may harness efficacious moieties of neuroprotective intent.
    MeSH terms: Humans; Neurons/metabolism; Apoptosis; alpha-Synuclein/genetics; alpha-Synuclein/metabolism
  16. Chau SC, Chong PS, Jin H, Tsui KC, Khairuddin S, Tse ACK, et al.
    Int J Mol Sci, 2023 Mar 23;24(7).
    PMID: 37047062 DOI: 10.3390/ijms24076089
    Cerebellar ataxia is a neurodegenerative disorder with no definitive treatment. Although previous study demonstrated the neuroprotective effects of Hericium erinaceus (H.E.), the mechanisms of H.E. treatment on the neuroinflammatory response, neurotransmission, and related metabolites remain largely unknown. We demonstrated that 3-AP rats treated with 25 mg/kg H.E. extracts had improved motor coordination and balance in the accelerated rotarod and rod tests. We showed that the H.E. treatment upregulated the expression of Tgfb1, Tgfb2, and Smad3 genes to levels comparable to those in the non-3-AP control group. Interestingly, we also observed a significant correlation between Tgfb2 gene expression and rod test performance in the 3-AP saline group, but not in the non-3-AP control or H.E.+3-AP groups, indicating a relationship between Tgfb2 gene expression and motor balance in the 3-AP rat model. Additionally, we also found that the H.E. treatment increased mitochondrial COX-IV protein expression and normalized dopamine-serotonin neurotransmission and metabolite levels in the cerebellum of the H.E.+3-AP group compared to the 3-AP saline group. In conclusion, our findings suggest that the H.E. treatment improved motor function in the 3-AP rat model, which was potentially mediated through neuroprotective mechanisms involving TGFB2-Smad3 signaling via normalization of neurotransmission and metabolic pathways.
    MeSH terms: Animals; Anti-Inflammatory Agents/therapeutic use; Disease Models, Animal; Rats
  17. Mohd Zawawi Z, Kalyanasundram J, Mohd Zain R, Thayan R, Basri DF, Yap WB
    Int J Mol Sci, 2023 Mar 24;24(7).
    PMID: 37047115 DOI: 10.3390/ijms24076142
    The coronavirus disease 2019 (COVID-19) became a worldwide concern at the beginning of 2020 and has affected millions. Several previous studies revealed the impact of the imbalanced innate immune response on the progression of COVID-19 and its disease outcomes. High levels of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins are produced readily by innate immune cells to fight Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infections. Nonetheless, cytokine-mediated inflammatory events are also linked to detrimental lung injury and respiratory failure, which can result in deaths among COVID-19 patients. TNF-α is amongst the early cytokines produced to mediate proinflammatory responses and enhance immune cell infiltration in response to SARS-CoV-2 infections. In COVID-19, TNF-α-mediated inflammation can cause detrimental tissue damage and gradually promotes lung fibrosis, which later results in pneumonia, pulmonary edema, and acute respiratory distress syndrome. This review, therefore, aims to deliberate the immunomodulatory roles of TNF-α in promoting inflammation and its relation with COVID-19 morbidity and mortality. In addition, this review also proposes the potential of TNF-α as a biomarker for the prognosis of severe COVID-19 and its related complications and as a molecular target for anti-TNF-α therapy.
    MeSH terms: Humans; Inflammation; Tumor Necrosis Factor-alpha; Cytokines
  18. Yusoff NA, Abd Hamid Z, Budin SB, Taib IS
    Int J Mol Sci, 2023 Mar 28;24(7).
    PMID: 37047305 DOI: 10.3390/ijms24076335
    Previous research reported that prolonged benzene exposure during in utero fetal development causes greater fetal abnormalities than in adult-stage exposure. This phenomenon increases the risk for disease development at the fetal stage, particularly carcinogenesis, which is mainly associated with hematological malignancies. Benzene has been reported to potentially act via multiple modes of action that target the hematopoietic stem cell (HSCs) niche, a complex microenvironment in which HSCs and multilineage hematopoietic stem and progenitor cells (HSPCs) reside. Oxidative stress, chromosomal aberration and epigenetic modification are among the known mechanisms mediating benzene-induced genetic and epigenetic modification in fetal stem cells leading to in utero carcinogenesis. Hence, it is crucial to monitor exposure to carcinogenic benzene via environmental, occupational or lifestyle factors among pregnant women. Benzene is a well-known cause of adult leukemia. However, proof of benzene involvement with childhood leukemia remains scarce despite previously reported research linking incidences of hematological disorders and maternal benzene exposure. Furthermore, accumulating evidence has shown that maternal benzene exposure is able to alter the developmental and functional properties of HSPCs, leading to hematological disorders in fetus and children. Since HSPCs are parental blood cells that regulate hematopoiesis during the fetal and adult stages, benzene exposure that targets HSPCs may induce damage to the population and trigger the development of hematological diseases. Therefore, the mechanism of in utero carcinogenicity by benzene in targeting fetal HSPCs is the primary focus of this review.
    MeSH terms: Child; Female; Fetus/pathology; Hematopoiesis; Hematopoietic Stem Cells/pathology; Humans; Pregnancy; Tumor Microenvironment; Carcinogenesis/pathology
  19. Abuhamad AY, Mohamad Zamberi NN, Vanharanta S, Mohd Yusuf SNH, Mohtar MA, Syafruddin SE
    Int J Mol Sci, 2023 Mar 29;24(7).
    PMID: 37047421 DOI: 10.3390/ijms24076447
    Clear cell renal cell carcinoma (ccRCC) is a hypervascular tumor that is characterized by bi-allelic inactivation of the VHL tumor suppressor gene and mTOR signalling pathway hyperactivation. The pro-angiogenic factor PDGFB, a transcriptional target of super enhancer-driven KLF6, can activate the mTORC1 signalling pathway in ccRCC. However, the detailed mechanisms of PDGFB-mediated mTORC1 activation in ccRCC have remained elusive. Here, we investigated whether ccRCC cells are able to secrete PDGFB into the extracellular milieu and stimulate mTORC1 signalling activity. We found that ccRCC cells secreted PDGFB extracellularly, and by utilizing KLF6- and PDGFB-engineered ccRCC cells, we showed that the level of PDGFB secretion was positively correlated with the expression of intracellular KLF6 and PDGFB. Moreover, the reintroduction of either KLF6 or PDGFB was able to sustain mTORC1 signalling activity in KLF6-targeted ccRCC cells. We further demonstrated that conditioned media of PDGFB-overexpressing ccRCC cells was able to re-activate mTORC1 activity in KLF6-targeted cells. In conclusion, cancer cell-derived PDGFB can mediate mTORC1 signalling pathway activation in ccRCC, further consolidating the link between the KLF6-PDGFB axis and the mTORC1 signalling pathway activity in ccRCC.
    MeSH terms: Humans; Gene Expression Regulation, Neoplastic; Proto-Oncogene Proteins c-sis/metabolism; Cell Line, Tumor; Von Hippel-Lindau Tumor Suppressor Protein/genetics
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