Displaying publications 21 - 40 of 97 in total

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  1. Wu YS, Looi CY, Subramaniam KS, Masamune A, Chung I
    Oncotarget, 2016 Jun 14;7(24):36719-36732.
    PMID: 27167341 DOI: 10.18632/oncotarget.9165
    Pancreatic stellate cells (PSC), a prominent stromal cell, contribute to the progression of pancreatic ductal adenocarcinoma (PDAC). We aim to investigate the mechanisms by which PSC promote cell proliferation in PDAC cell lines, BxPC-3 and AsPC-1. PSC-conditioned media (PSC-CM) induced proliferation of these cells in a dose- and time-dependent manner. Nrf2 protein was upregulated and subsequently, its transcriptional activity was increased with greater DNA binding activity and transcription of target genes. Downregulation of Nrf2 led to suppression of PSC-CM activity in BxPC-3, but not in AsPC-1 cells. However, overexpression of Nrf2 alone resulted in increased cell proliferation in both cell lines, and treatment with PSC-CM further enhanced this effect. Activation of Nrf2 pathway resulted in upregulation of metabolic genes involved in pentose phosphate pathway, glutaminolysis and glutathione biosynthesis. Downregulation and inhibition of glucose-6-phosphate-dehydrogenase with siRNA and chemical approaches reduced PSC-mediated cell proliferation. Among the cytokines present in PSC-CM, stromal-derived factor-1 alpha (SDF-1α) and interleukin-6 (IL-6) activated Nrf2 pathway to induce cell proliferation in both cells, as shown with neutralization antibodies, recombinant proteins and signaling inhibitors. Taken together, SDF-1α and IL-6 secreted from PSC induced PDAC cell proliferation via Nrf2-activated metabolic reprogramming and ROS detoxification.
  2. Dawe K, Montgomery A, McGee H, Panagopoulou E, Morgan K, Hackshaw L, et al.
    J Health Psychol, 2016 05;21(5):607-18.
    PMID: 24829376 DOI: 10.1177/1359105314532970
    We synthesised evidence on biological correlates of psychological stress in hospital-based healthcare professionals, and examined whether there was evidence of consistent biological changes. Electronic databases were searched for empirical studies; 16 articles (0.6%) met the inclusion criteria. Evidence of a relationship between indices of psychological stress and biological parameters was limited and inconsistent. There was some evidence of a consistent relationship between natural killer cells and lymphocyte subpopulations. Considerable heterogeneity in the methods used was seen. Future prospective studies examining the relationship between indices of psychological stress and natural killer cells, including lymphocyte subsets, is required.
  3. Subramaniam KS, Tham ST, Mohamed Z, Woo YL, Mat Adenan NA, Chung I
    PLoS One, 2013;8(7):e68923.
    PMID: 23922669 DOI: 10.1371/journal.pone.0068923
    Endometrial cancer is the most commonly diagnosed gynecologic malignancy worldwide; yet the tumor microenvironment, especially the fibroblast cells surrounding the cancer cells, is poorly understood. We established four primary cultures of fibroblasts from human endometrial cancer tissues (cancer-associated fibroblasts, CAFs) using antibody-conjugated magnetic bead isolation. These relatively homogenous fibroblast cultures expressed fibroblast markers (CD90, vimentin and alpha-smooth muscle actin) and hormonal (estrogen and progesterone) receptors. Conditioned media collected from CAFs induced a dose-dependent proliferation of both primary cultures and cell lines of endometrial cancer in vitro (175%) when compared to non-treated cells, in contrast to those from normal endometrial fibroblast cell line (51%) (P<0.0001). These effects were not observed in fibroblast culture derived from benign endometrial hyperplasia tissues, indicating the specificity of CAFs in affecting endometrial cancer cell proliferation. To determine the mechanism underlying the differential fibroblast effects, we compared the activation of PI3K/Akt and MAPK/Erk pathways in endometrial cancer cells following treatment with normal fibroblasts- and CAFs-conditioned media. Western blot analysis showed that the expression of both phosphorylated forms of Akt and Erk were significantly down-regulated in normal fibroblasts-treated cells, but were up-regulated/maintained in CAFs-treated cells. Treatment with specific inhibitors LY294002 and U0126 reversed the CAFs-mediated cell proliferation (P<0.0001), suggesting for a role of these pathways in modulating endometrial cancer cell proliferation. Rapamycin, which targets a downstream molecule in PI3K pathway (mTOR), also suppressed CAFs-induced cell proliferation by inducing apoptosis. Cytokine profiling analysis revealed that CAFs secrete higher levels of macrophage chemoattractant protein (MCP)-1, interleukin (IL)-6, IL-8, RANTES and vascular endothelial growth factor (VEGF) than normal fibroblasts. Our data suggests that in contrast to normal fibroblasts, CAFs may exhibit a pro-tumorigenic effect in the progression of endometrial cancer, and PI3K/Akt and MAPK/Erk signaling may represent critical regulators in how endometrial cancer cells respond to their microenvironment.
  4. Katherason SG, Naing L, Jaalam K, Nik Mohamad NA, Bhojwani K, Harussani ND, et al.
    J Infect Dev Ctries, 2010 Mar 08;4(2):118-23.
    PMID: 20212345
    BACKGROUND: Hand decontamination is a critical infection control practice in the prevention of nosocomial infection. This study was conducted to observe the hand hygiene practices of nurses and doctors in two intensive care units (ICUs) in Malaysia.

    METHODOLOGY: Staff members were observed during patient contacts, and their hand washing techniques and hand hygiene practices were monitored. Five contact periods were observed for staff members while they cared for their assigned patients. Hand hygiene practices before and after patient contacts were categorized as clean uncontaminated, clean recontaminated, new gloves, and unchanged contaminated gloves. Compliance to hand-washing steps and time taken for hand washing were analyzed. Appropriate use of gloves based on CDC criteria also was assessed.

    RESULTS: Compliance to hand hygiene practices was 70% before each patient contact. Staff members did not completely adhere to the hand-washing steps. The average time taken to wash hands was 20 seconds, and the necessary steps (rubbing palm over dorsum; rubbing fingers interlaced, and rotational rubbing of thumbs) were practiced minimally by all staff. Hand washing protocol was generally followed by all staff (100%). Alcohol hand rubs were available but were used moderately (60%); when used, staff members did not wait for the alcohol to dry. Only 4% of staff changed contaminated gloves between patients.

    CONCLUSIONS: Hand hygiene compliance by ICU staff members needs to be improved. Improving adherence to correct hand hygiene techniques will require effective education programs and behavioral modification techniques. Moreover, hand hygiene guidelines must be incorporated into new staff orientation programs and the continuing education curriculum in the two hospitals studied.

  5. Subramaniam KS, Omar IS, Kwong SC, Mohamed Z, Woo YL, Mat Adenan NA, et al.
    Am J Cancer Res, 2016;6(2):200-13.
    PMID: 27186396
    Cancer-associated fibroblasts (CAFs) secrete various pro-tumorigenic cytokines, yet the role of these cytokines in the progression of endometrial cancer remains unclear. We found that CAFs isolated from human endometrial cancer (EC) tissues secreted high levels of interleukin-6 (IL-6), which promotes EC cell proliferation in vitro. Neutralizing IL-6 in CAF-conditioned media reduced (47% inhibition) while IL-6 recombinant protein increased cell proliferation (~2.4 fold) of both EC cell lines and primary cultures. IL-6 receptors (IL-6R and gp130) were expressed only in EC epithelial cells but not in CAF, indicating a one-way paracrine signaling. In the presence of CAF-conditioned media, Janus kinase/signal transducers and activators of transcription (JAK/STAT3) pathway was activated in EC cells. Treatment with JAK and STAT3 specific inhibitors, AD412 and STATTIC, respectively, significantly abrogated CAF-mediated cell proliferation, indicating the role of IL-6 activation in EC cell proliferation. We further showed that one of STAT-3 target genes, c-Myc, was highly induced in EC cells after exposure to CAF-conditioned medium at both mRNA (>105-fold vs. control) and protein level (>2-fold vs. control). EC cell proliferation was dependent on c-Myc expression, as RNAi-mediated c-Myc down-regulation led to a significant 46% reduction in cell viability when compared with scrambled control. Interestingly, CAF-conditioned media failed to promote proliferation in EC cells with reduced c-Myc expression, suggesting that CAF-mediated cell proliferation was also dependent on c-Myc expression. Subcutaneous tumor xenograft model showed that EC cells grew at least 1.4 times larger when co-injected with CAF, when compared to those injected with EC cells alone. Mice injected with EC cells with down-regulated c-Myc expression, however, showed at least 2.5 times smaller tumor compared to those in control group. Notably, there was no increase of tumor size when co-injected with CAFs. Further immunohistochemical staining on human tissues showed positive expression of IL-6 receptors, phosphorylated-STAT3 and c-Myc in human EC tissues with less signals in benign endometrium. Taken together, our data suggests that IL-6 secreted by CAF induces c-Myc expression to promote EC proliferation in vitro and in vivo. IL-6 pathway can be a potential target to disrupt tumor-stroma interaction in endometrial cancer progression.
  6. Yang SP, Ying LS, Saw S, Tuttle RM, Venkataraman K, Su-Ynn C
    Endocr Pract, 2015 Nov;21(11):1255-68.
    PMID: 26247114 DOI: 10.4158/EP15850.OR
    OBJECTIVE: Numerous published guidelines have described the optimal management of thyroid cancer. However, these rely on the clinical availability of diagnostic and therapeutic modalities. We hypothesized that the availability of medical resources and economic circumstances vary in Asia-Pacific countries, making it difficult to implement guideline recommendations into clinical practice.

    METHODS: We surveyed participants at the 2009 and 2013 Congresses of the Association of Southeast Asian Nations Federation of Endocrine Societies by distributing questionnaires to attendees at registration.

    RESULTS: Responses were obtained from 268 respondents in 2009 and 163 respondents in 2013. Similar to the high prevalence of low-risk thyroid cancer observed in the Surveillance, Epidemiology, and End Results database, across the Asia-Pacific countries surveyed in 2009 and 2013, 50 to 100% of the respondents from the Philippines, Malaysia, Singapore, China, Taiwan, Thailand, Hong Kong, Korea, and Sri Lanka reported that more than 50% of the patients had low-risk thyroid cancer on follow-up. Importantly, there was much variation with regards to the perceived availability of investigation and treatment modalities.

    CONCLUSION: We found a wide variation in clinicians' perception of availability of diagnostic and therapeutic modalities in the face of a rise in thyroid cancer incidence and thyroid cancer management guidelines that emphasized their importance. The lack of availability of management tools and treatments will prove to be a major barrier to the implementation of thyroid cancer management guidelines in Southeast Asia, and likely in other parts of the world as well.

  7. Lai LW, Roslani AC, Yan YW, Bhojwani KM, Jamaluddin MFH
    ANZ J Surg, 2021 05;91(5):896-901.
    PMID: 33522667 DOI: 10.1111/ans.16567
    BACKGROUND: Conventional mass closure uses suture-to-wound length ratio of 4:1 ('long stitch', LS). 'Short stitch' (SS) has a suture-to-wound length ratio of more than 4 and incorporates only the linea alba, which may reduce tension and pain. We compared the post-operative pain after laparotomy closure using LS and SS.

    METHODS: Patients undergoing elective midline laparotomy through standardized incisions in two tertiary hospitals from February 2017 to September 2018 were randomized to either LS or SS. The primary outcome was post-operative patient-controlled analgesia morphine usage at 24 h. Secondary outcomes were presence of surgical site infection and length of hospital stay (LOHS). Categorical variables were analysed using chi-squared analysis. Outcomes of study were tested for normal distribution. Skewed data were analysed using Mann-Whitney U-test.

    RESULTS: Eighty-six patients were recruited (42 SS and 44 LS). The median age was 66 (interquartile range (IQR) 15). Majority were males (62.8%) and Chinese (50%). The median incision length was 17 cm in both groups. The median patient-controlled analgesia morphine usage 24 h post-operatively did not differ significantly (SS 21 mg, IQR 28.3; LS 18.5 mg, IQR 33.8, P = 0.829). The median pain score at rest (SS 1, IQR 1; LS 1, IQR 2, P = 0.426) and movement (SS 3, IQR 1; LS 3, IQR 2, P = 0.307) did not differ significantly. LOHS was shorter in the SS group (SS 6, IQR 4; LS 8, IQR 5, P = 0.034). The rate of surgical site infection trended lower in the SS group with no statistical difference.

    CONCLUSION: There were no differences in post-operative pain between SS and LS but we found that there were shorter LOHS in SS arm as secondary outcome.

  8. Chen WH, Chang CM, Mutuku JK, Lam SS, Lee WJ
    Environ Res, 2021 06;197:110975.
    PMID: 33689824 DOI: 10.1016/j.envres.2021.110975
    The deposition phenomenon of microparticle and SAR-CoV-2 laced bioaerosol in human airways is studied by Taguchi methods and response surface methodology (RSM). The data used herein is obtained from simulations of airflow dynamics and deposition fractions of drug particle aerosols in the downstream airways of asthma patients using computational fluid dynamics (CFD) and discrete particle motion (DPM). Three main parameters, including airflow rate, drug dose, and particle size, affecting aerosol deposition in the lungs of asthma patients are examined. The highest deposition fraction (DF) is obtained at the flow rate of 45 L min-1, the drug dose of 200 μg·puff-1, and the particle diameter of 5 μm. The optimized combination of levels for the three parameters for maximum drug deposition is performed via the Taguchi method. The importance of the influencing factors rank as particle size > drug dose > flow rate. RSM reveals that the combination of 30 L min-1, 5 μm, 200 μg·puff- has the highest deposition fraction. In part, this research also studied the deposition of bioaerosols contaminated with the SAR-CoV-2 virus, and their lowest DF is 1.15%. The low DF of bioaerosols reduces the probability of the SAR-CoV-2 virus transmission.
  9. Chen WH, Chang CM, Mutuku JK, Lam SS, Lee WJ
    J Hazard Mater, 2021 08 15;416:125856.
    PMID: 34492805 DOI: 10.1016/j.jhazmat.2021.125856
    Inhalation of aerosols such as pharmaceutical aerosols or virus aerosol uptake is of great concern to the human population. To elucidate the underlying aerosol dynamics, the deposition fractions (DFs) of aerosols in healthy and asthmatic human airways of generations 13-15 are predicted. The Navier-stokes equations governing the gaseous phase and the discrete phase model for particles' motion are solved using numerical methods. The main forces responsible for deposition are inertial impaction forces and complex secondary flow velocities. The curvatures and sinusoidal folds in the asthmatic geometry lead to the formation of complex secondary flows and hence higher DFs. The intensities of complex secondary flows are strongest at the generations affected by asthma. The DF in the healthy airways is 0%, and it ranges from 1.69% to 52.93% in the asthmatic ones. From this study, the effects of the pharmaceutical aerosol particle diameters in the treatment of asthma patients can be established, which is conducive to inhibiting the inflammation of asthma airways. Furthermore, with the recent development of COVID-19 which causes pneumonia, the predicted physics and effective simulation methods of bioaerosols delivery to asthma patients are vital to prevent the exacerbation of the chronic ailment and the epidemic.
  10. Reginald K, Tan CL, Chen S, Yuen L, Goh SY, Chew FT
    Sci Rep, 2018 08 06;8(1):11743.
    PMID: 30082894 DOI: 10.1038/s41598-018-30224-z
    We previously identified an expressed sequence tag clone, Der f 22, showing 41% amino acid identity to published Der f 2, and show that both genes are possible paralogues. The objective of this study was to characterize the genomic, proteomic and immunological functions Der f 22 and Der f 2. The full-length sequence of Der f 2 and Der f 22 coded for mature proteins of 129 and 135 amino acids respectively, both containing 6 cysteine residues. Phylogenetic analysis of known group 2 allergens and their homologues from our expressed sequence tag library showed that Der f 22 is a paralogue of Der f 2. Both Der f 2 and Der f 22 were single gene products with one intron. Both allergens showed specific IgE-binding to over 40% of the atopic patients, with limited of cross-reactivity. Both allergens were detected at the gut region of D. farinae by immunostaining. Der f 22 is an important allergen with significant IgE reactivity among the atopic population, and should be considered in the diagnostic panel and evaluated as future hypoallergen vaccine therapeutic target.
  11. Singh Y, Gupta G, Satija S, Pabreja K, Chellappan DK, Dua K
    Drug Dev Res, 2020 09;81(6):647-649.
    PMID: 32329083 DOI: 10.1002/ddr.21674
  12. Kavita A, Abdul Onny MA, Suppiah S, Abdul Aziz AF, Hashim H, Raja Shariff RE, et al.
    Med J Malaysia, 2021 Sep;76(5):762-767.
    PMID: 34508392
    Cardiac amyloidosis (CA) is a rare form of protein deposition disease, leading to restrictive cardiomyopathy that often presents with signs and symptoms of unexplained heart failure with preserved ejection fraction (HFpEF). There are two main subtypes of CA, namely light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), which are conventionally confirmed by endomyocardial biopsy (EMB). The prognosis and treatment of the subtypes differ extensively, making it crucial to distinguish between the two. Although echocardiography (ECHO) and cardiac magnetic resonance imaging (CMR) are useful to aid in the diagnosis, they are unable to differentiate between the subtypes. Advantageously, the transthyretin cardiac amyloidosis (ATTR-CA) subtype can be diagnosed based on nuclear medicine bone scintigraphy imaging using Technetiumlabelled bone-seeking radiotracers. We report a case of a previously well, elderly gentleman who presented with acute heart failure symptoms, whereby ECHO findings were suspicious for CA. Technetium-99m pyrophosphate (99mTc- PYP) bone scintigraphy performed with complementary single photon emission computed tomography/computed tomography (SPECT/CT) at three hours post-injection revealed radiotracer uptake in the myocardium that was higher than the skeletal bone uptake. This corresponded to Perugini score of 3 along with an increased heart to contralateral lung ratio (H:CL) of 1.69. The bone scintigraphy findings together with his symptoms, ECHO, CMR, and laboratory results enabled the diagnosis of ATTR-CA to be made. In summary, bone scintigraphy offers a reliable and non-invasive method for the diagnosis of ATTR-CA. We also highlight the diagnostic pitfalls and recommendations in reporting bone scintigraphy for the indication of typing cardiac amyloidosis.
  13. Satyavert, Gupta S, Choudhury H, Jacob S, Nair AB, Dhanawat M, et al.
    Pharmacol Rep, 2021 Dec;73(6):1734-1743.
    PMID: 34283375 DOI: 10.1007/s43440-021-00312-5
    BACKGROUND: Curcumin, a natural polyphenol from Curcuma longa, is known to possess diversified pharmacological roles including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic properties; however, its bioavailability is severely limited due to its poor solubility, poor absorption, rapid metabolism, and significant elimination. Hydrazinocurcumin (HZC), a novel analogue of curcumin has been reported to overcome the limitations of curcumin and also possesses multiple pharmacological activities. The present study aimed to evaluate the unexplored pharmacokinetic profile of this agent in experimental rats.

    METHODS: Drug formulations were administered to the experimental animals via oral, intravenous and intraperitoneal routes. Blood samples were collected at different pre-determined time intervals to determine the pharmacokinetic parameters. To understand the biodistribution profile of HCZ, tissue samples were isolated from different groups of Sprague-Dawley rats at different time points. The pharmacokinetic parameters of HZC were evaluated after administration through oral (100 mg/kg), intraperitoneal (100 mg/kg) and intravenous (10 mg/kg) routes.

    RESULTS: Significantly (p 

  14. Reginald K, Wong YR, Shah SMR, Teh KF, Freddy Jalin EJ, Khan NA
    Microbes Infect, 2021 07 28;23(9-10):104876.
    PMID: 34332091 DOI: 10.1016/j.micinf.2021.104876
    BACKGROUND: Insects models are excellent models of the innate immune system, as they are free from the influences of vertebrate adaptive immunity. Crickets are hemimetabolous insects belonging to the order Orthopteran order that have not been as extensively characterized as other holometabolous insects, and may provide new insights into the insect immune responses. In this study, we aim to characterize the innate immune responses of the common house cricket, Acheta domesticus in response to a human pathogenic bacterium E. coli K1.

    METHODS: Crickets were injected with sterile buffer, live E. coli K1 or heat-killed E. coli K1. Physiological effects such as mortality and weight change of the crickets were determined 24-, 48- and 72-h post injection while immunological effects such as hemocyte counts, bacteremia, phenoloxidase and lysozyme activity of the crickets were measured at 2- and 24-h post-injection.

    RESULTS: The injection of E. coli K1 in crickets resulted in >85% mortality 3-days post injection, accompanied by significant weight loss. E. coli K1 injection caused a significant increase in both phenoloxidase and lysozyme activities in cricket hemolymphs 24-h post injection. Live E. coli K1 injected crickets resulted in a significant reduction in circulating hemocytes 24-h post injection which was not observed in other treatment groups. This was consistent with the resolution of bacteremia observed 24-h post infection in live E. coli K1 injected crickets.

    CONCLUSION: Our study provides new insights on the innate immune response to pathogenic E. coli K1 in a cricket model.

  15. Siner A, Liew ST, Kadir KA, Mohamad DSA, Thomas FK, Zulkarnaen M, et al.
    Malar J, 2017 Oct 17;16(1):417.
    PMID: 29041929 DOI: 10.1186/s12936-017-2064-9
    BACKGROUND: Plasmodium knowlesi, a simian malaria parasite, has become the main cause of malaria in Sarawak, Malaysian Borneo. Epidemiological data on malaria for Sarawak has been derived solely from hospitalized patients, and more accurate epidemiological data on malaria is necessary. Therefore, a longitudinal study of communities affected by knowlesi malaria was undertaken.

    METHODS: A total of 3002 blood samples on filter paper were collected from 555 inhabitants of 8 longhouses with recently reported knowlesi malaria cases in the Betong Division of Sarawak, Malaysian Borneo. Each longhouse was visited bimonthly for a total of 10 times during a 21-month study period (Jan 2014-Oct 2015). DNA extracted from blood spots were examined by a nested PCR assay for Plasmodium and positive samples were then examined by nested PCR assays for Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, Plasmodium knowlesi, Plasmodium cynomolgi and Plasmodium inui. Blood films of samples positive by PCR were also examined by microscopy.

    RESULTS: Genus-specific PCR assay detected Plasmodium DNA in 9 out of 3002 samples. Species-specific PCR identified 7 P. knowlesi and one P. vivax. Malaria parasites were observed in 5 thick blood films of the PCR positive samples. No parasites were observed in blood films from one knowlesi-, one vivax- and the genus-positive samples. Only one of 7 P. knowlesi-infected individual was febrile and had sought medical treatment at Betong Hospital the day after sampling. The 6 knowlesi-, one vivax- and one Plasmodium-infected individuals were afebrile and did not seek any medical treatment.

    CONCLUSIONS: Asymptomatic human P. knowlesi and P. vivax malaria infections, but not P. cynomolgi and P. inui infections, are occurring within communities affected with malaria.

  16. Siner A, Liew ST, Kadir KA, Mohamad DSA, Thomas FK, Zulkarnaen M, et al.
    Malar J, 2017 11 06;16(1):445.
    PMID: 29110664 DOI: 10.1186/s12936-017-2093-4
    After publication of the article [1], it has been brought to our attention that two of the labels on Figure 4 have transposed. The labels "S-type SSU rRNA" and "A-type SSU rRNA" should be in opposite places.
  17. Gupta G, Chellappan DK, Agarwal M, Ashwathanarayana M, Nammi S, Pabreja K, et al.
    Cent Nerv Syst Agents Med Chem, 2017;17(3):196-200.
    PMID: 27834136 DOI: 10.2174/1871524917666161111095335
    BACKGROUND: Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory deficiencies. In Chinese medicine, Morus alba is used as a neuroprotective herb. The current study was intended to discover the recuperative effect of morusin against aluminium trichloride (AlCl3)-induced memory impairment in rats along with biochemical mechanism of its protective action.

    METHODS: Memory deficiency was produced by AlCl3 (100 mg/kg; p.o.) in experimental animals. Learning and memory activity was measured using Morris water maze (MWM) test model. Central cholinergic activity was evaluated through the measurement of brain acetylcholinesterase (AChE) activity. In addition to the above, oxidative stress was determined through assessment of brain thiobarbituric acid-reactive species (TBARS) and glutathione (GSH) levels.

    RESULTS: AlCl3 administration prompted significant deficiency of learning and memory in rats, as specified by a noticeable reduction in MWM presentation. AlCl3 administration also produced a significant deterioration in brain AChE action and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Treatment with morusin (5.0 and 10.0 mg/kg, dose orally) significantly overturned AlCl3- induced learning and memory shortages along with diminution of AlCl3-induced rise in brain AChE activity and brain oxidative stress levels.

    CONCLUSION: It may be concluded that morusin exerts a memory-preservative outcome in mental discrepancies of rats feasibly through its various activities.

  18. Lim JJ, Reginald K, Say YH, Liu MH, Chew FT
    Int Arch Allergy Immunol, 2023;184(10):975-984.
    PMID: 37393903 DOI: 10.1159/000530948
    INTRODUCTION: Frequent dietary patterns for fast food diets are suggested to be a risk factor for atopic disease development. Excessive dietary fats in fast foods are postulated to promote low-grade chronic inflammation. However, no studies in Asia have yet to characterize the dietary pattern for high-fat foods with atopic diseases. Thus, this study aims to assess the association between dietary fats with the prevalence of atopic diseases in an allergic cohort.

    METHODS: Through an investigator-administered questionnaire that follows the International Study of Asthma and Allergies in Childhood (ISAAC) protocol, we evaluated the eating habits, lifestyle behaviours, sociodemographics, and atopic symptoms, and history among 11,494 young Chinese adults in Singapore and Malaysia. A skin prick test (SPT) for common house dust mites was also conducted to determine the atopic (allergic) status. We identified 1,550 atopic dermatitis (AD), 1,301 allergic asthma (AS), and 3,757 allergic rhinitis (AR) atopic cases. We derived a novel dietary index, Diet Quality based on Total Fat Amount (DQTFA), to examine the association between eating patterns for estimated total fat amount with various atopic outcomes.

    RESULTS: There was a preponderance of subjects having positive SPT reaction (69.0%) with the prevalence of AR being the highest (32.7%), then AD (13.5%), and AS (11.3%). Additionally, there is a significantly higher proportion of subjects with an atopy background and atopic diseases consume diets with a high estimated mean fat amount. The adherence to a dietary pattern of the higher estimated total fat amount was shown to be strongly associated with all atopic diseases and exhibited dose-dependent responses in the univariate analysis. These associations remained significant even with the adjustments for age, gender, body mass index, use of alcohol, sedentary lifestyles, and physical activity. A dietary pattern for high-fat amount is more strongly associated with AS (adjusted odds ratio [AOR]: 1.524; 95% confidence interval [CI]: 1.216-1.725; p < 0.001) and AR (AOR: 1.294; 95% CI: 1.107-1.512; p < 0.001) compared to AD (AOR: 1.278; 95% CI: 1.049-1.559; p < 0.05). Finally, it was shown that having either one of the atopic comorbidities was strongly associated with a dietary pattern of high-fat amounts (AOR: 1.360; 95% CI: 1.161-1.594; p < 0.001).

    CONCLUSION: Our findings altogether provide initial evidence that the dietary pattern of a diet high in fat amount is associated with an increased risk of atopy and atopic diseases in young Chinese adults in Singapore and Malaysia. Balancing the consumption of dietary fats and changing personal dietary habits by choosing foods of the lower fat amount may reduce the associated odds of atopic diseases.

  19. Lim JJ, Reginald K, Say YH, Liu MH, Chew FT
    BMC Public Health, 2023 Sep 19;23(1):1818.
    PMID: 37726698 DOI: 10.1186/s12889-023-16736-y
    BACKGROUND: The prevalence of atopic dermatitis (AD) has been increasing in recent years, especially in Asia. There is growing evidence to suggest the importance of dietary patterns in the development and management of AD. Here, we seek to understand how certain dietary patterns in a Singapore/Malaysia population are associated with various risks of AD development and exacerbation.

    METHODS: A standardized questionnaire following the International Study of Asthma and Allergies in Childhood (ISAAC) guidelines was investigator-administered to a clinically and epidemiology well-defined allergic cohort of 13,561 young Chinese adults aged 19-22. Information on their sociodemographic, lifestyle, dietary habits, and personal and family medical atopic histories were obtained. Allergic sensitization was assessed by a skin prick test to mite allergens. Spearman's rank-order correlation was used to assess the correlation between the intake frequencies of 16 food types. Dietary patterns were identified using principal component analysis. Four corresponding dietary scores were derived to examine the association of identified dietary patterns with allergic sensitization and AD exacerbations through a multivariable logistic regression that controlled for age, gender, parental eczema, BMI, and lifestyle factors.

    RESULTS: The correlation is the strongest between the intake of butter and margarine (R = 0.65). We identified four dietary patterns, "high-calorie foods", "plant-based foods", "meat and rice", and "probiotics, milk and eggs", and these accounted for 47.4% of the variance in the dietary habits among the subjects. Among these patterns, moderate-to-high intake of "plant-based foods" conferred a negative association for chronic (Adjusted odds ratio (AOR): 0.706; 95% confidence interval (CI): 0.589-0.847; p 

  20. Abd El-Aal AAA, Jayakumar FA, Lahiri C, Tan KO, Reginald K
    Sci Rep, 2023 Sep 06;13(1):14673.
    PMID: 37673929 DOI: 10.1038/s41598-023-41581-9
    Cryptides are a subfamily of bioactive peptides that exist in all living organisms. They are latently encrypted in their parent sequences and exhibit a wide range of biological activities when decrypted via in vivo or in vitro proteases. Cationic cryptides tend to be drawn to the negatively charged membranes of microbial and cancer cells, causing cell death through various mechanisms. This makes them promising candidates for alternative antimicrobial and anti-cancer therapies, as their mechanism of action is independent of gene mutations. In the current study, we employed an in silico approach to identify novel cationic cryptides with potential antimicrobial and anti-cancer activities in atypical and systematic strategy by reanalysis of a publicly available RNA-seq dataset of Pacific white shrimp (Penaus vannamei) in response to bacterial infection. Out of 12 cryptides identified, five were selected based on their net charges and potential for cell penetration. Following chemical synthesis, the cryptides were assayed in vitro to test for their biological activities. All five cryptides demonstrated a wide range of selective activity against the tested microbial and cancer cells, their anti-biofilm activities against mature biofilms, and their ability to interact with Gram-positive and negative bacterial membranes. Our research provides a framework for a comprehensive analysis of transcriptomes in various organisms to uncover novel bioactive cationic cryptides. This represents a significant step forward in combating the crisis of multi-drug-resistant microbial and cancer cells, as these cryptides neither induce mutations nor are influenced by mutations in the cells they target.
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