Displaying publications 41 - 60 of 73 in total

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  1. Fulltext Oxidative stress-induced premature senescence in Wharton's jelly-derived mesenchymal stem cells
    Choo KB, Tai L, Hymavathee KS, Wong CY, Nguyen PN, Huang CJ, et al.
    Int J Med Sci, 2014;11(11):1201-7.
    PMID: 25249788 DOI: 10.7150/ijms.8356
    On in vitro expansion for therapeutic purposes, the regenerative potentials of mesenchymal stem cells (MSCs) decline and rapidly enter pre-mature senescence probably involving oxidative stress. To develop strategies to prevent or slow down the decline of regenerative potentials in MSC culture, it is important to first address damages caused by oxidative stress-induced premature senescence (OSIPS). However, most existing OSIPS study models involve either long-term culture to achieve growth arrest or immediate growth arrest post oxidative agent treatment and are unsuitable for post-induction studies.
  2. Fulltext PIK3CA gene amplification and PI3K p110α protein expression in breast carcinoma
    Firoozinia M, Zareian Jahromi M, Moghadamtousi SZ, Nikzad S, Abdul Kadir H
    Int J Med Sci, 2014;11(6):620-5.
    PMID: 24782652 DOI: 10.7150/ijms.8251
    A family of PI3Ks is the lipid kinases, which enhance intracellular pools of phosphatidyl inositol 3,4,5-tri-phosphate (PIP3) through phosphorylating its precursor. Amplifications and deletions of genes, as well as somatic missense of the PIK3CA gene have been described in many human cancer varieties, including of the brain, colon, liver, lung and stomach. Immunohistochemistry and Real-time quantitative PCR tests were used to determine the PIK3CA gene amplification (gene copy number) and to detect protein expression, respectively. The results obtained were analysed and the ratio of PIK3CA to β-actin gene copy number was calculated. Positive gene amplification of PIK3CA was appointed as a copy number of ≥4. Also, PI3K p110α protein expression was scored from 0 to 3+ and the scores of 2+ and 3+ were considered as positive for PI3K p110α protein expression. We studied 50 breast carcinoma samples for PI3K p110α protein expression and PIK3CA gene copy numbers. In general, 36 out of 50 (72%) breast carcinoma samples showed a significant increase in PIK3CA gene amplification. 12 out of 50 (24%) showed positive staining, and 38 out of 50 (76%) showed negative staining for PI3K p110α expression. We have identified no significant relationship between PIK3CA amplification, race (p= 0.630) and histological type (p=0. 731) in breast carcinoma, but correlation of PIK3CA amplification and age showed a significant relationship (p=0. 003) between them. No significant relationship has been identified in correlation of PI3K p110α protein expression compared to age (p=0. 284), race (p=0. 546) and histological type (p=0. 285). Amplification of PIK3CA was frequent in breast carcinoma and occurs in stages of breast carcinoma. Our result shows that there is a relationship between gene amplification and age in breast carcinoma. We suggest that PIK3CA is significant in breast tumorigenesis serve as a prevalent mechanism contributes to the oncogenic activation pathway of PIK3CA in breast cancer.
  3. Fulltext Papillary Thyroid Cancer: Genetic Alterations and Molecular Biomarker Investigations
    Abdullah MI, Junit SM, Ng KL, Jayapalan JJ, Karikalan B, Hashim OH
    Int J Med Sci, 2019;16(3):450-460.
    PMID: 30911279 DOI: 10.7150/ijms.29935
    Papillary thyroid cancer (PTC) is the most prevalent form of malignancy among all cancers of the thyroid. It is also one of the few cancers with a rapidly increasing incidence. PTC is usually contained within the thyroid gland and generally biologically indolent. Prognosis of the cancer is excellent, with less than 2% mortality at 5 years. However, more than 25% of patients with PTC developed a recurrence during a long term follow-up. The present article provides an updated condensed overview of PTC, which focuses mainly on the molecular alterations involved and recent biomarker investigations.
  4. Fulltext Paratyphoid fever: splicing the global analyses
    Teh CS, Chua KH, Thong KL
    Int J Med Sci, 2014;11(7):732-41.
    PMID: 24904229 DOI: 10.7150/ijms.7768
    The incidence of enteric fever caused by Salmonella enterica serovar Paratyphi A (S. Paratyphi A) is increasing in many parts of the world. Although there is no major outbreak of paratyphoid fever in recent years, S. Paratyphi A infection still remains a public health problem in many tropical countries. Therefore, surveillance studies play an important role in monitoring infections and the emergence of multidrug resistance, especially in endemic countries such as India, Nepal, Pakistan and China. In China, enteric fever was caused predominantly by S. Paratyphi A rather than by Salmonella enterica serovar Typhi (S. Typhi). Sometimes, S. Paratyphi A infection can evolve into a carrier state which increases the risk of transmission for travellers. Hence, paratyphoid fever is usually classified as a "travel-associated" disease. To date, diagnosis of paratyphoid fever based on the clinical presentation is not satisfactory as it resembles other febrile illnesses, and could not be distinguished from S. Typhi infection. With the availability of Whole Genome Sequencing technology, the genomes of S. Paratyphi A could be studied in-depth and more specific targets for detection will be revealed. Hence, detection of S. Paratyphi A with Polymerase Chain Reaction (PCR) method appears to be a more reliable approach compared to the Widal test. On the other hand, due to increasing incidence of S. Paratyphi A infections worldwide, the need to produce a paratyphoid vaccine is essential and urgent. Hence various vaccine projects that involve clinical trials have been carried out. Overall, this review provides the insights of S. Paratyphi A, including the bacteriology, epidemiology, management and antibiotic susceptibility, diagnoses and vaccine development.
  5. Fulltext Peptides as Therapeutic Agents for Dengue Virus
    Chew MF, Poh KS, Poh CL
    Int J Med Sci, 2017;14(13):1342-1359.
    PMID: 29200948 DOI: 10.7150/ijms.21875
    Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.
  6. Fulltext Positive association between metabolic syndrome and bone mineral density among Malaysians
    Chin KY, Chan CY, Subramaniam S, Muhammad N, Fairus A, Ng PY, et al.
    Int J Med Sci, 2020;17(16):2585-2593.
    PMID: 33029101 DOI: 10.7150/ijms.49030
    Objectives: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that elevates the individual risk of cardiovascular diseases. These abnormalities are also known to alter bone remodelling. Therefore, MetS may be associated with osteoporosis. This study aims to determine the association between MetS and its components and bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) among Malaysians. Methods: 400 Malaysians aged ≥ 40 years (52.5% women) residing in Klang Valley, Malaysia, were recruited. Subjects' demographic and lifestyle details were collected using a questionnaire, and blood pressure and body anthropometry were measured. Subjects' lumbar spine and total hip BMD were measured by DXA. Their fasting blood was collected for blood glucose level and lipid profile analysis. Regression analysis was used to analyze the relationship between MetS or its components and BMD. Results: Subjects with MetS had higher BMD compared to subjects without MetS in models unadjusted for BMI (spine p=0.008; hip p<0.001). This difference was attenuated with BMI adjustment (spine p=0.625; hip p=0.478). Waist circumference was associated positively with BMD in models unadjusted for BMI (spine p=0.012; hip p<0.001), but the association became negative with BMI adjustment (spine p=0.044; hip p=0.021). Systolic blood pressure was associated positively with total hip BMD (p=0.019) but BMI adjustment attenuated the relationship (p=0.080). Triglyceride level was associated with osteoporosis in a fully adjusted model (p=0.001). Overall, MetS was associated with osteoporosis (p=0.019) but lifestyle (p=0.188) and BMI adjustment attenuated the relationship (p=0.904). Conclusion: MetS is positively associated with BMD, and this relationship is predominantly mediated by BMI. Although MetS is not a significant risk factor for osteoporosis, the inverse relationship between waist circumference, a marker of central obesity, and BMD highlights the need to prevent adiposity to improve metabolic and skeletal health.
  7. Fulltext Potential immunogenic polypeptides of Burkholderia pseudomallei identified by shotgun expression library and evaluation of their efficacy for serodiagnosis of melioidosis
    Puah SM, Puthucheary SD, Chua KH
    Int J Med Sci, 2013;10(5):539-47.
    PMID: 23532805 DOI: 10.7150/ijms.5516
    The search for novel immunogenic polypeptides to improve the accuracy and reliability of serologic diagnostic methods for Burkholderia pseudomallei infection is ongoing. We employed a rapid and efficient approach to identify such polypeptides with sera from melioidosis patients using a small insert genomic expression library created from clinically confirmed local virulent isolates of B. pseudomallei. After 2 rounds of immunoscreening, 6 sero-positive clones expressing immunogenic peptides were sequenced and their identities were: benzoate 1,2-dioxygenase beta subunit, a putative 200 kDa antigen p200, phosphotransferase enzyme family protein, short chain dehydrogenase and 2 hypothetical proteins. These immunogens were then transferred to an ELISA platform for further large scale screening. By combining shotgun expression library and ELISA assays, we identified 2 polypeptides BPSS1904 (benzoate 1,2-dioxygenase beta subunit) and BPSL3130 (hypothetical protein), which had sensitivities of 78.9% and 79.4% and specificities of 88.1% and 94.8%, respectively in ELISA test, thus suggesting that both are potential candidate antigens for the serodiagnosis of infections caused by B. pseudomallei.
  8. Fulltext Potential mechanisms linking psychological stress to bone health
    Ng JS, Chin KY
    Int J Med Sci, 2021;18(3):604-614.
    PMID: 33437195 DOI: 10.7150/ijms.50680
    Chronic psychological stress affects many body systems, including the skeleton, through various mechanisms. This review aims to provide an overview of the factors mediating the relationship between psychological stress and bone health. These factors can be divided into physiological and behavioural changes induced by psychological stress. The physiological factors involve endocrinological changes, such as increased glucocorticoids, prolactin, leptin and parathyroid hormone levels and reduced gonadal hormones. Low-grade inflammation and hyperactivation of the sympathetic nervous system during psychological stress are also physiological changes detrimental to bone health. The behavioural changes during mental stress, such as altered dietary pattern, cigarette smoking, alcoholism and physical inactivity, also threaten the skeletal system. Psychological stress may be partly responsible for epigenetic regulation of skeletal development. It may also mediate the relationship between socioeconomic status and bone health. However, more direct evidence is required to prove these hypotheses. In conclusion, chronic psychological stress should be recognised as a risk factor of osteoporosis and stress-coping methods should be incorporated as part of the comprehensive osteoporosis-preventing strategy.
  9. Fulltext Pre-operative serum alkaline phosphatase as a predictor for hypocalcemia post-parathyroid adenectomy
    Loke SC, Tan AW, Dalan R, Leow MK
    Int J Med Sci, 2012;9(7):611-6.
    PMID: 23028244 DOI: 10.7150/ijms.4861
    Post-operative hypocalcemia (POH) may complicate parathyroidectomy for primary hyperparathyroidism. This study investigates the relationship between POH and pre-operative risk factors to identify a simple method to predict POH risk.
  10. Fulltext Recombinant human adiponectin as a potential protein for treating diabetic tendinopathy promotes tenocyte progenitor cells proliferation and tenogenic differentiation in vitro
    Rothan HA, Suhaeb AM, Kamarul T
    Int J Med Sci, 2013;10(13):1899-906.
    PMID: 24324367 DOI: 10.7150/ijms.6774
    Adiponectin is an adipocyte-secreting hormone that increases cell sensitivity to insulin. It has been previously demonstrated that this hormone protects against Type II Diabetes and, is found to concurrently promote cell proliferation and differentiation. It is postulated that diabetic patients who suffer from tendinopathy may benefit from using adiponectin, which not only improves the metabolism of diabetic ridden tenocytes but also promotes progenitor cell proliferation and differentiation in tendons. These changes may result in tendon regeneration, which, in diabetic tendinopathy, is difficult to treat. Considering that such findings have yet to be demonstrated, a study was thus conducted using diabetic ridden human tenocyte progenitor cells (TPC) exposed to recombinant adiponectin in vitro. TPC were isolated from tendons of diabetic patients and exposed to 10 μg/ml adiponectin. Cell proliferation rate was investigated at various time points whilst qPCR were used to determine the tenogenic differentiation potential. The results showed that adiponectin significantly reduced blood glucose in animal models. The proliferation rate of adiponectin-treated TPCs was significantly higher at 6, 8 and 10 days as compared to untreated cells (p<0.05). The levels of tenogenic genes expression (collagen I, III, tenomodulin and scleraxis) were also significantly upregulated; whilst the osteogenic (Runx2), chondrogenic (Sox9) and adipogenic (PPARУγ) gene expressions remained unaltered. The results of this study suggest that adiponectin is a potential promoter that not only improves diabetic conditions, but also increases tendon progenitor cell proliferation and differentiation. These features supports the notion that adiponectin may be potentially beneficial in treating diabetic tendinopathy.
  11. Fulltext Repurposing New Use for Old Drug Chloroquine against Metabolic Syndrome: A Review on Animal and Human Evidence
    Wong SK
    Int J Med Sci, 2021;18(12):2673-2688.
    PMID: 34104100 DOI: 10.7150/ijms.58147
    Chloroquine (CQ) and hydroxychloroquine (HCQ) are traditional anti-malarial drugs that have been repurposed for new therapeutic uses in many diseases due to their simple usage and cost-effectiveness. The pleiotropic effects of CQ and HCQ in regulating blood pressure, glucose homeostasis, lipid, and carbohydrate metabolism have been previously described in vivo and in humans, thus suggesting their role in metabolic syndrome (MetS) prevention. The anti-hyperglycaemic, anti-hyperlipidaemic, cardioprotective, anti-hypertensive, and anti-obesity effects of CQ and HCQ might be elicited through reduction of inflammatory response and oxidative stress, improvement of endothelial function, activation of insulin signalling pathway, inhibition of lipogenesis and autophagy, as well as regulation of adipokines and apoptosis. In conclusion, the current state of knowledge supported the repurposing of CQ and HCQ usage in the management of MetS.
  12. Fulltext Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells
    Phang WM, Tan AA, Gopinath SC, Hashim OH, Kiew LV, Chen Y
    Int J Med Sci, 2016;13(5):330-9.
    PMID: 27226773 DOI: 10.7150/ijms.14341
    Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer.
  13. Fulltext Self-emulsified annatto tocotrienol improves bone histomorphometric parameters in a rat model of oestrogen deficiency through suppression of skeletal sclerostin level and RANKL/OPG ratio
    Mohamad NV, Ima-Nirwana S, Chin KY
    Int J Med Sci, 2021;18(16):3665-3673.
    PMID: 34790038 DOI: 10.7150/ijms.64045
    Menopause is the leading cause of osteoporosis for elderly women due to imbalanced bone remodelling in the absence of oestrogen. The ability of tocotrienol in reversing established bone loss due to oestrogen deficiency remains unclear despite the plenitude of evidence showcasing its preventive effects. This study aimed to investigate the effects of self-emulsified annatto tocotrienol (SEAT) on bone histomorphometry and remodelling in ovariectomised rats. Female Sprague Dawley rats (n=36) were randomly assigned into baseline, sham, ovariectomised (OVX) control, OVX-treated with annatto tocotrienol (AT) (60 mg/kg), SEAT (60 mg/kg) and raloxifene (1 mg/kg). Daily treatment given through oral gavage was started two months after castration. The rats were euthanised after eight weeks of treatment. Blood was collected for bone biomarkers. Femur and lumbar bones were collected for histomorphometry and remodelling markers. The results showed that AT and SEAT improved osteoblast numbers and trabecular mineralisation rate (p<0.05 vs untreated OVX). AT also decreased skeletal sclerostin expression in OVX rats (p<0.05 vs untreated OVX). Similar effects were observed in the raloxifene-treated group. Only SEAT significantly increased bone formation rate and reduced RANKL/OPG ratio (p<0.05 vs untreated OVX). However, no changes in osteoclast-related parameters were observed among the groups (p>0.05). In conclusion, SEAT exerts potential skeletal anabolic properties by increasing bone formation, suppressing sclerostin expression and reducing RANKL/OPG ratio in rats with oestrogen deficiency.
  14. Fulltext Senescence affects endothelial cells susceptibility to dengue virus infection
    AbuBakar S, Shu MH, Johari J, Wong PF
    Int J Med Sci, 2014;11(6):538-44.
    PMID: 24782642 DOI: 10.7150/ijms.7896
    Alteration in the endothelium leading to increased vascular permeability contributes to plasma leakage seen in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). An earlier study showed that senescent endothelial cells (ECs) altered the ECs permeability. Here we investigated the susceptibility of senescing human umbilical vein endothelial cells (HUVECs) to dengue virus infection and determined if dengue virus infection induces HUVECs senescence. Our results suggest that DENV type-2 (DENV-2) foci forming unit (FFU) and extracellular virus RNA copy number were reduced by at least 35% and 85% in infection of the intermediate young and early senescent HUVECs, respectively, in comparison to infection of young HUVECs. No to low infectivity was recovered from infection of late senescent HUVECs. DENV infection also increases the percentage of HUVECs expressing senescence-associated (SA)-β-gal, cells arrested at the G2/M phase or 4N DNA content stage and cells with enlarged morphology, indicative of senescing cells. Alteration of HUVECs morphology was recorded using impedance-based real-time cell analysis system following DENV-2 infection. These results suggest that senescing HUVECs do not support DENV infection and DENV infection induces HUVECs senescence. The finding highlights the possible role of induction of senescence in DENV infection of the endothelial cells.
  15. Fulltext Serum osteocalcin is significantly related to indices of obesity and lipid profile in Malaysian men
    Chin KY, Ima-Nirwana S, Mohamed IN, Ahmad F, Ramli ES, Aminuddin A, et al.
    Int J Med Sci, 2014;11(2):151-7.
    PMID: 24465160 DOI: 10.7150/ijms.7152
    Recent studies revealed a possible reciprocal relationship between the skeletal system and obesity and lipid metabolism, mediated by osteocalcin, an osteoblast-specific protein. This study aimed to validate the relationship between serum osteocalcin and indices of obesity and lipid parameters in a group of Malaysian men.
  16. Fulltext Sex-steroid regulation of relaxin receptor isoforms (RXFP1 & RXFP2) expression in the patellar tendon and lateral collateral ligament of female WKY rats
    Dehghan F, Muniandy S, Yusof A, Salleh N
    Int J Med Sci, 2014;11(2):180-91.
    PMID: 24465164 DOI: 10.7150/ijms.6283
    The incidence of non-contact knee injury was found higher in female than in male and is related to the phases of the menstrual cycle. This raised the possibility that female sex-steroids are involved in the mechanism underlying this injury via affecting the expression of the receptors for relaxin, a peptide hormone known to modulate ligament laxity. Therefore, this study aims to investigate the effect of sex-steroids on relaxin receptor isoforms (RXFP1 & RXFP2) expression in the ligaments and tendons of the knee.

    METHODS: Ovariectomized adult female WKY rats were treated with different doses of estrogen (0.2, 2, 20 μg/kg), progesterone (4mg) and testosterone (125 & 250μg/kg) for three consecutive days. At the end of the treatment, the animals were sacrificed and the patellar tendon and lateral collateral ligament were harvested for mRNA and protein expression analyses by Real Time PCR and Western blotting respectively.

    RESULTS: RXFP1, the main isoform expressed in these knee structures and RXFP2 showed a dose-dependent increase in expression with estrogen. Progesterone treatment resulted in an increase while testosterone caused a dose-dependent decrease in the mRNA and protein expression of both relaxin receptor isoforms.

    DISCUSSION: Progesterone and high dose estrogen up-regulate while testosterone down-regulates RXFP1 and RXFP2 expression in the patellar tendon and lateral collateral ligament of rat's knee.

    CONCLUSION: Relaxin receptor isoforms up-regulation by progesterone and high dose estrogen could provide the basis for the reported increase in knee laxity while down-regulation of these receptor isoforms by testosterone could explain low incidence of non-contact knee injury in male.

  17. Fulltext Smoking and Unstable Plaque in Acute Coronary Syndrome: A Systematic Review of The Role of Matrix Metalloproteinases
    Aminuddin A, Cheong SS, Roos NAC, Ugusman A
    Int J Med Sci, 2023;20(4):482-492.
    PMID: 37057211 DOI: 10.7150/ijms.79889
    Smoking is a risk factor of acute coronary syndrome (ACS) that could increase matrix metalloproteinases (MMPs) levels, leading to unstable coronary artery plaque. The current review aimed to identify the relationship between smoking and MMPs in patients with ACS. Literature search was conducted from inception until March 2022 in three online databases. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was performed, and the odds ratio (OR) together with its 95% confidence interval (CI) were determined. A total of 7,843 articles were identified, and only seven studies were included. Four studies investigated the MMP-3 and MMP-9 related genes and found that smokers with certain MMPs genotypes had high risk of ACS. Smoking also increased the MMPs level in patients with ACS compared with non-smokers. Additionally, a meta-analysis of two studies resulted in an increased odd of ACS in smokers with MMP-3 5A allele versus non-smokers with MMP-3 6A6A allele (OR: 15.94, 95% CI: 10.63-23.92; I2 =55%). In conclusion, the current review highlights the role of MMPs in relation to smoking and ACS. The determination of these roles may help in identifying new ACS markers among smokers and the development of drug-targeted treatment.
  18. Fulltext T Cell Immunity To Enterovirus 71 Infection In Humans And Implications For Vaccine Development
    Yee PTI, Poh CL
    Int J Med Sci, 2018;15(11):1143-1152.
    PMID: 30123051 DOI: 10.7150/ijms.26450
    Enterovirus 71 (EV-A71) is one of the major pathogens causing hand, foot and mouth disease (HFMD). Some strains can lead to neurological disease and fatality in children. Up to date, there is no FDA-approved vaccine to prevent severe HFMD and mortality. Although the inactivated vaccine has advanced to production in China, lack of long-term protection and the requirement of multiple boosters have necessitated the development of other types of vaccines. Recent studies indicate that cellular and not humoral immunity determines the clinical outcome of EV-A71 infections. High levels of cytokines such as IL-1β, IL-6, IL-10 and IFN-γ tend to correlate with clinical severity in patients with pulmonary edema and encephalitis. The live attenuated vaccine may serve as the preferred choice as it can induce excellent humoral and cellular immunity as well as live-long immunity. Expression of certain HLA alleles such as TNF-α promoter type II (-308 allele), HLA-A33 and HLA-DR17 responses have been linked to severe HFMD. However, the high variability of MHC genes could restrict T cell recognition and be a major obstacle in the design of peptide vaccines. Hence, the development of a T cell universal vaccine (incorporating both CD4+ and CD8+ T cell epitopes) that induces broad, multifunctional and cross-reactive CD8+ T cell responses maybe desirable.
  19. Fulltext The Conserved Molecular Determinants of Virulence in Dengue Virus
    Ahmad Z, Poh CL
    Int J Med Sci, 2019;16(3):355-365.
    PMID: 30911269 DOI: 10.7150/ijms.29938
    Dengue virus belongs to the Flaviviridae family which also includes viruses such as the Zika, West Nile and yellow fever virus. Dengue virus generally causes mild disease, however, more severe forms of the dengue virus infection, dengue haemorrhagic fever (DHF) and dengue haemorrhagic fever with shock syndrome (DSS) can also occur, resulting in multiple organ failure and even death, especially in children. The only dengue vaccine available in the market, CYD-TDV offers limited coverage for vaccinees from 9-45 years of age and is only recommended for individuals with prior dengue exposure. A number of mutations that were shown to attenuate virulence of dengue virus in vitro and/or in vivo have been identified in the literature. The mutations which fall within the conserved regions of all four dengue serotypes are discussed. This review hopes to provide information leading to the construction of a live attenuated dengue vaccine that is suitable for all ages, irrespective of the infecting dengue serotype and prior dengue exposure.
  20. Fulltext The Emerging Roles of π Subunit-Containing GABAA Receptors in Different Cancers
    Juvale IIA, Hassan Z, Has ATC
    Int J Med Sci, 2021;18(16):3851-3860.
    PMID: 34790061 DOI: 10.7150/ijms.60928
    Cancer is one of the leading causes of death in both developed and developing countries. Due to its heterogenous nature, it occurs in various regions of the body and often goes undetected until later stages of disease progression. Feasible treatment options are limited because of the invasive nature of cancer and often result in detrimental side-effects and poor survival rates. Therefore, recent studies have attempted to identify aberrant expression levels of previously undiscovered proteins in cancer, with the hope of developing better diagnostic tools and pharmaceutical options. One class of such targets is the π-subunit-containing γ-aminobutyric acid type A receptors. Although these receptors were discovered more than 20 years ago, there is limited information available. They possess atypical functional properties and are expressed in several non-neuronal tissues. Prior studies have highlighted the role of these receptors in the female reproductive system. New research focusing on the higher expression levels of these receptors in ovarian, breast, gastric, cervical, and pancreatic cancers, their physiological function in healthy individuals, and their pro-tumorigenic effects in these cancer types is reviewed here.
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