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Endoscopic transnasal approach to medial orbital lesions

Tan SH, Prepageran N

J Laryngol Otol, 2015 Sep;129(9):928-31.
PMID: 26193981 DOI: 10.1017/S0022215115001838

This case report presents our experience of endoscopic transnasal management of medial intra- and extraconal lesions.
Fulltext Comparison on phytochemical constituents in the patchouli oil of in vitro and ex vitro pogostemon cablin leaves

Wan Nurul Hidayah, W. A., Putri Shareen, R, Nur Atirah, H., Tan, S. H.

ESTEEM Academic Journal, 2021;17(2):123-134.
MyJurnal

Pogostemon cablin (patchouli) is a medicinal herb well known for its
essential oil derived from the leaves. Patchouli oil shows excellent base note
in fragrance industries for its fixatives properties and its patchouli alcohol
(patchoulol) is used as quality indicator for its oil. However, the P. cablin is
the only commercial source of patchoulol and cannot be obtained
synthetically in the laboratory. Higher demand in the production of its
essential oil gave a significant contribution for in vitro grown P.cablin to
meet the market supply for industries. Hence, in this study, the essential oil
in both in vitro and ex vitro P.cablin were extracted from its leaves by means
of hydrodistillation method and its phytochemical constituents were
identified and compared using Gas Chromatography Mass Spectrometry.
The yield and quality of its essential oil from both in vitro and ex vitro
P.cablin’s leaves were investigated. In vitro patchouli essential oil extraction
gaves higher yield (40 ml) than the ex vitro patchouli essential oil (26 ml)
under similar condition for hydrodistillation. Six major components were
identified through GC-MS and was compared between two samples which
are β- patchoulene, Caryophyllene, α- guaiene, α- cedrene, α- bulnesene and
Patchouli alcohol. The patchoulol, which is the main constituents that is
important in fixative had doubled (42.18 %) in the in vitro P.cablin essential
oil compared to ex vitro (29.24%). This finding was reflected based on the
peak area percentage of each substance through GC-MS. Other constituents
in the in vitro P.cablin were found still competitive to the ex vitro in slightly
lower values. Overall, in vitro P.cablin showed higher yield and quality
compared to the ex vitro grown P.cablin.
Pneumo-orbita causing optic nerve compression

Tan SH, Prepageran N

QJM, 2018 Oct 01;111(10):743.
PMID: 29660085 DOI: 10.1093/qjmed/hcy084
Narrow band imaging for sulcus vocalis-an often missed diagnosis

Tan SH, Sombuntham P

QJM, 2023 Feb 14;116(1):69-70.
PMID: 35993912 DOI: 10.1093/qjmed/hcac204
Isolation and characterization of cDNA clones encoding ADP-glucose pyrophosphorylase from sago palm (Metroxylon sagu)

Au SL, Tan SH, Harikrishna K, Napis S

J. Biochem. Mol. Biol. Biophys., 2002 Oct;6(5):301-8.
PMID: 12385964

Four ADP-glucose pyrophosphorylase cDNA clones were isolated from mature leaves and pith of sago palm by the polymerase chain reaction (PCR) technique. Three of them (agpp10, agpp12 and agpl19) encoded the AGP large subunit, while the fourth clone (agpl1) encoded the small subunit. agpp10 and agpp12 were isolated from pith, agpl19 was isolated from mature leaves, while agpl1 from both tissues. In addition, a full-length cDNA of agpl1 was successfully isolated from a cDNA library of mature leaves by a PCR-based screening technique. Semi-quantitative analysis suggests that agpp10 and agpp12 were detectable only in pith, agpl19 only in leaves, while agpl1 was expressed in both leaves and pith tissues.
Fulltext A new record of Iranihindia martellata (Senior-White,1924) (Diptera: Sarcophagidae) from peninsular Malaysia and female identification using both morphology and DNA-based approaches

Tan SH, Mohd Aris E, Kurahashi H, Mohamed Z

Trop Biomed, 2010 Aug;27(2):287-93.
PMID: 20962727

Iranihindia martellata (Senior-White, 1924) is recorded from peninsular Malaysia for the first time. Male and female specimens in the recent collections of forensically important sarcophagid flies were examined and identified based on morphology and DNA sequencing analysis. Male genitalia offer unambiguous species identification characteristics in the traditional taxonomy of flesh flies but the female flies are very similar to one another in general morphology. Female of I. martellata was determined by DNA sequencing (COI and COII) and PCR-RFLP (COI) analysis. Identified females were carefully examined and compared with the morphologically similar species, Liopygia ruficornis (Fabricius, 1794). Female genitalia are re-described and illustrated in this paper.
The cloning of Ty1-copia-like retrotransposons from 10 varieties of banana (Musa Sp.)

Teo CH, Tan SH, Othman YR, Schwarzacher T

J. Biochem. Mol. Biol. Biophys., 2002 Jun;6(3):193-201.
PMID: 12186754

Ty1-copia-like retrotransposons have been identified and investigated in several plant species. Here, the internal region of the reverse transcriptase (RT) gene of Ty1-copia-like retrotransposons was amplified by PCR from total genomic DNA of 10 varieties of banana. Two to four clones from each variety were sequenced. Extreme heterogeneity in the sequences of Ty1-copia-like retrotransposons from all the varieties was revealed following sequence analysis of the reverse transcriptase (RT) fragments. The size of the individual RT gene fragments varied between 213 and 309 bp. Southern blots of genomic DNA digested from Musa acuminata and other banana varieties probed with W8 clone from M. acuminata and A4 clone from Pisang Abu Nipah showed similar strong, multiple restriction fragments together with other faint hybridization band patterns with variable intensities indicating the presence of many copies of the Ty1-copia-like retrotransposons in the genomes. There was no correlation between retroelement sequence and the banana species (with A or B genomes) from which it arose, suggesting that the probes are not useful for tracking genomes through breeding populations.
Coxsackievirus A16 in a 1-Day-Old Mouse Model of Central Nervous System Infection Shows Lower Neurovirulence than Enterovirus A71

Hooi YT, Ong KC, Tan SH, Perera D, Wong KT

J Comp Pathol, 2020 Apr;176:19-32.
PMID: 32359633 DOI: 10.1016/j.jcpa.2020.02.001

Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) are the major causes of hand, foot and mouth disease in young children. Although less so with CV-A16, both viruses are associated with serious neurological syndromes, but the differences between their central nervous system infections remain unclear. We conducted a comparative infection study using clinically-isolated CV-A16 and EV-A71 strains in a 1-day-old mouse model to better understand the neuropathology and neurovirulence of the viruses. New serotype-specific probes for in situ hybridization were developed and validated to detect CV-A16 and EV-A71 RNA in infected tissues. Demonstration of CV-A16 virus antigens/RNA, mainly in the brainstem and spinal cord neurons, confirmed neurovirulence, but showed lower densities than in EV-A71 infected animals. A higher lethal dose50 for CV-A16 suggested that CV-A16 is less neurovirulent. Focal virus antigens/RNA in the anterior horn white matter and adjacent efferent motor nerves suggested that neuroinvasion is possibly via retrograde axonal transport in peripheral motor nerves.
In vitro antiviral activity of medicinal mushroom Ganoderma neo-japonicum Imazeki against enteroviruses that caused hand, foot and mouth disease

Ang WX, Sarasvathy S, Kuppusamy UR, Sabaratnam V, Tan SH, Wong KT, et al.

Trop Biomed, 2021 Sep 01;38(3):239-247.
PMID: 34362866 DOI: 10.47665/tb.38.3.063

Hand, foot and mouth disease (HFMD) is a highly contagious viral disease that predominantly affects children younger than 5 years old. HFMD is primarily caused by enterovirus A71 (EVA71) and coxsackievirus A16 (CV-A16). However, coxsackievirus A10 (CV-A10) and coxsackievirus A6 (CV-A6) are being increasingly reported as the predominant causative of HFMD outbreaks worldwide since the past decade. To date, there are still no licensed multivalent vaccines or antiviral drugs targeting enteroviruses that cause HFMD, despite HFMD outbreaks are still being frequently reported, especially in Asia-Pacific countries. The high rate of transmission, morbidity and potential neurological complications of HFMD is indeed making the development of broad-spectrum antiviral drugs/agents against these enteroviruses a compelling need. In this study, we have investigated the in vitro antiviral effect of 4 Ganoderma neo-japonicum Imazeki (GNJI) crude extracts (S1-S4) against EV-A71, CV-A16, CV-A10 and CV-A6. GNJI is a medicinal mushroom that can be found growing saprophytically on decaying bamboo clumps in Malaysian forests. The antiviral effects of this medicinal mushroom were determined using cytopathic inhibition and virus titration assays. The S2 (1.25 mg/ml) hot aqueous extract demonstrated the highest broad-spectrum antiviral activity against all tested enteroviruses in human primary oral fibroblast cells. Replication of EV-A71, CV-A16 and CVA10 were effectively inhibited at 2 hours post-infection (hpi) to 72 hpi, except for CV-A6 which was only at 2 hpi. S2 also has virucidal activity against EV-A71. Polysaccharides isolated and purified from crude hot aqueous extract demonstrated similar antiviral activity as S2, suggesting that polysaccharides could be one of the active compounds responsible for the antiviral activity shown by S2. To our knowledge, this study demonstrates for the first time the ability of GNJI to inhibit enterovirus infection and replication. Thus, GNJI is potential to be further developed as an antiviral agent against enteroviruses that caused HFMD.
Antiviral activity of povidone-iodine gargle and mouthwash solution against Enterovirus A71, Coxsackieviruses A16, A10 and A6

Ang WX, Tan SH, Wong KT, Perera D, Kuppusamy UR, Ong KC

Trop Biomed, 2024 Sep 01;41(3):241-250.
PMID: 39548776 DOI: 10.47665/tb.41.3.002

Hand, Foot and Mouth Disease (HFMD), a highly contagious viral disease common among infants and young children, is primarily caused by Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA16). Nonetheless, emerging enteroviruses, such as CV-A10 and CV-A6, have also caused widespread outbreaks globally, in part due to the absence of effective antiviral therapies, and the high personto-person transmission rate. Person-to-person transmission is usually through fecal-oral or oral-oral routes, and sometimes via droplets. As the oral cavity is a primary site for early virus infection and replication, controlling oral viral shedding can mitigate the risk of transmission through this route. Povidone-iodine (PVP-I), a widely used antiseptic, has shown broad-spectrum antimicrobial properties but antiviral studies against HFMD-causing enteroviruses are limited, especially for CV-A10 and CVA6. Our study demonstrated that a 1% PVP-I solution (final concentration of 0.5%) exhibited virucidal activity against EV-A71, CV-A16, CV-A10, and CV-A6. All seven EV-A71 isolates and five CV-A16 isolates showed a significant virus titer reduction after a 1-minute incubation, while five CV-A10 isolates and two CV-A6 isolates required a 5-minute incubation to achieve this. The virucidal activity was confirmed through the EN14476:2013+A2:2019 virucidal quantitative suspension test, wherein all four viruses were completely inactivated after a 30-minute incubation with PVP-I at 37°C under both clean and dirty conditions. Western blot analysis suggested that PVP-I could affect the VP1 structural proteins of EV-A71. Our results suggest that PVP-I could serve as a potential virucidal agent to reduce the risk of person-to-person transmission of HFMD.
Fulltext Mutant p53-R273H mediates cancer cell survival and anoikis resistance through AKT-dependent suppression of BCL2-modifying factor (BMF)

Tan BS, Tiong KH, Choo HL, Chung FF, Hii LW, Tan SH, et al.

Cell Death Dis, 2015;6:e1826.
PMID: 26181206 DOI: 10.1038/cddis.2015.191

p53 is the most frequently mutated tumor-suppressor gene in human cancers. Unlike other tumor-suppressor genes, p53 mutations mainly occur as missense mutations within the DNA-binding domain, leading to the expression of full-length mutant p53 protein. Mutant p53 proteins not only lose their tumor-suppressor function, but may also gain new oncogenic functions and promote tumorigenesis. Here, we showed that silencing of endogenous p53-R273H contact mutant, but not p53-R175H conformational mutant, reduced AKT phosphorylation, induced BCL2-modifying factor (BMF) expression, sensitized BIM dissociation from BCL-XL and induced mitochondria-dependent apoptosis in cancer cells. Importantly, cancer cells harboring endogenous p53-R273H mutant were also found to be inherently resistant to anoikis and lack BMF induction following culture in suspension. Underlying these activities is the ability of p53-R273H mutant to suppress BMF expression that is dependent on constitutively active PI3K/AKT signaling. Collectively, these findings suggest that p53-R273H can specifically drive AKT signaling and suppress BMF expression, resulting in enhanced cell survivability and anoikis resistance. These findings open the possibility that blocking of PI3K/AKT will have therapeutic benefit in mutant p53-R273H expressing cancers.
Gemcitabine, carboplatin, and Epstein Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized Phase 3 trial

Toh HC, Yang MH, Wang HM, Hsieh CY, Chitapanarux I, Ho KF, et al.

Ann Oncol, 2024 Sep 04.
PMID: 39241963 DOI: 10.1016/j.annonc.2024.08.2344

BACKGROUND: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous Phase 2 trial of locally recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective anti-tumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared to conventional chemotherapy treatment.
PATIENTS AND METHODS: This multicenter, randomized, Phase 3 trial evaluated the efficacy and safety of GC followed by EBV-CTL vs. GC alone as first-line treatment for R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the United States (US) were included. Subjects were randomized to first-line GC (4 cycles) and EBV-CTL (6 cycles) or GC (6 cycles) in a 1:1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety.
CLINICALTRIALS: gov identifier: NCT02578641.
RESULTS: 330 subjects with NPC were enrolled. Most subjects in both treatment arms received ≥4 cycles of chemotherapy and most subjects in the GC+EBV-CTL group received ≥2 infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC+EBV-CTL subjects. The median OS was 25.0 months in the GC+EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% CI: 0.91, 1.56; P = 0.194). Only 1 subject experienced a Grade 2 serious adverse event related to EBV-CTL.
CONCLUSION: GC+EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS vs. chemotherapy. This is the largest adoptive T cell therapy trial reported in solid tumors to date.
Fulltext The aquaculture supply chain in the time of covid-19 pandemic: Vulnerability, resilience, solutions and priorities at the global scale

Mangano MC, Berlino M, Corbari L, Milisenda G, Lucchese M, Terzo S, et al.

Environ Sci Policy, 2022 Jan;127:98-110.
PMID: 34720746 DOI: 10.1016/j.envsci.2021.10.014

The COVID-19 global pandemic has had severe, unpredictable and synchronous impacts on all levels of perishable food supply chains (PFSC), across multiple sectors and spatial scales. Aquaculture plays a vital and rapidly expanding role in food security, in some cases overtaking wild caught fisheries in the production of high-quality animal protein in this PFSC. We performed a rapid global assessment to evaluate the effects of the COVID-19 pandemic and related emerging control measures on the aquaculture supply chain. Socio-economic effects of the pandemic were analysed by surveying the perceptions of stakeholders, who were asked to describe potential supply-side disruption, vulnerabilities and resilience patterns along the production pipeline with four main supply chain components: a) hatchery, b) production/processing, c) distribution/logistics and d) market. We also assessed different farming strategies, comparing land- vs. sea-based systems; extensive vs. intensive methods; and with and without integrated multi-trophic aquaculture, IMTA. In addition to evaluating levels and sources of economic distress, interviewees were asked to identify mitigation solutions adopted at local / internal (i.e., farm-site) scales, and to express their preference on national / external scale mitigation measures among a set of a priori options. Survey responses identified the potential causes of disruption, ripple effects, sources of food insecurity, and socio-economic conflicts. They also pointed to various levels of mitigation strategies. The collated evidence represents a first baseline useful to address future disaster-driven responses, to reinforce the resilience of the sector and to facilitate the design reconstruction plans and mitigation measures, such as financial aid strategies.

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