Browse publications by year: 2016

  1. Mohd Kamil A, Draman CR, Seman MR, Kalavathy R, Mubarak MY
    Saudi J Kidney Dis Transpl, 2016 Jul-Aug;27(4):787-90.
    PMID: 27424699 DOI: 10.4103/1319-2442.185259
    Malignancy is a significant long-term complication of successful renal transplantation. Not only the rate is higher but also cases are highly aggressive. We report a case of metastatic, small cell, neuroendocrine tumor in a post-renal transplant patient with progressive left inguinal nodes and right lumbar swellings. He had a remarkably elevated serum lactate dehydrogenase levels with multiple metastatic masses in the left inguinal, left iliac fossa, and right lower abdominal wall on abdominal computed tomography scan. Excisional biopsy of a left inguinal node revealed extensive infiltration with malignant cells in it. Immunohistochemistry staining was positive for synaptophysin, prostatic specific antigen, and CD56. While the primary small cell carcinoma of genitourinary organs is rare, the case illustrates the highly aggressive nature of the disease in a kidney transplant recipient.
    MeSH terms: Humans; Kidney; Kidney Neoplasms; Lymphatic Metastasis; Male; Kidney Transplantation; Neuroendocrine Tumors*
  2. Jameel RA, Khan SS, Abdul Rahim ZH, Bakri MM, Siddiqui S
    J Pak Med Assoc, 2016 Jul;66(7):843-8.
    PMID: 27427133
    To understand early dental erosion induced by different beverages and the equipment for its detection.
  3. Chin YT, Lim YA, Chong CW, Teh CS, Yap IK, Lee SC, et al.
    Infect Dis Poverty, 2016;5(1):77.
    PMID: 27430215 DOI: 10.1186/s40249-016-0168-z
    Intestinal parasitic infections (IPIs) among indigenous people have been widely documented in Malaysia, however, the prevalence of these infections remains high. In the past, most studies have focused on specific species of parasites but polyparasitism has received limited attention. In addition, epidemiology studies on indigenous people tend to consider them as a homogenous group, whereas in reality different sub-ethnic groups have different cultural and living practices. Variations in living habits such as personal hygiene practices may predispose different groups to different parasitic infections. To better understand prevalence and risk factors of intestinal parasitism among different sub-ethnic groups, the present study was conducted among two sub-ethnic groups of indigenous people (Temuan and Mah Meri) residing in Selangor state, Malaysia.
  4. Brant HL, Ewers RM, Vythilingam I, Drakeley C, Benedick S, Mumford JD
    Malar J, 2016 07 19;15(1):370.
    PMID: 27430261 DOI: 10.1186/s12936-016-1416-1
    BACKGROUND: Malaria cases caused by Plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques, are increasing rapidly in Sabah, Malaysia. One hypothesis is that this increase is associated with changes in land use. A study was carried out to identify the anopheline vectors present in different forest types and to observe the human landing behaviour of mosquitoes.

    METHODS: Mosquito collections were carried out using human landing catches at ground and canopy levels in the Tawau Division of Sabah. Collections were conducted along an anthropogenic disturbance gradient (primary forest, lightly logged virgin jungle reserve and salvage logged forest) between 18:00 and 22:00 h.

    RESULTS: Anopheles balabacensis, a vector of P. knowlesi, was the predominant species in all collection areas, accounting for 70 % of the total catch, with a peak landing time of 18:30-20:00 h. Anopheles balabacensis had a preference for landing on humans at ground level compared to the canopy (p 

    MeSH terms: Animals; Anopheles/parasitology; Anopheles/physiology*; Feeding Behavior*; Humans; Malaysia; Plasmodium knowlesi/isolation & purification; Rainforest*; Mosquito Vectors/physiology*
  5. Rashid M, Tiwari AK, Goss JP, Rayson MJ, Briddon PR, Horsfall AB
    Phys Chem Chem Phys, 2016 Aug 03;18(31):21676-85.
    PMID: 27430278 DOI: 10.1039/c6cp03775e
    Density functional calculations are performed for OH-, F- and H-terminated 4H-SiC 10-20 Å diameter clusters to investigate the effect of surface species upon the optical absorption properties. H-termination results in a pronounced size-dependent quantum-confinement in the absorption, whereas F- and OH-terminations exhibit much reduced size dependent absorption due to surface states. Our findings are in good agreement with recent experimental studies, and are able to explain the little explored dual-feature photoluminescence spectra of SiC quantum dots. We propose that along with controlling the size, suitable surface termination is the key for optimizing optical properties of 4H-SiC quantum structures, such as might be exploited in optoelectronics, photovoltaics and biological applications.
  6. Do TC, Boettiger D, Law M, Pujari S, Zhang F, Chaiwarith R, et al.
    HIV Med, 2016 08;17(7):542-9.
    PMID: 27430354 DOI: 10.1111/hiv.12358
    OBJECTIVES: The aim of the study was to assess the prevalence and characteristics associated with current smoking in an Asian HIV-positive cohort, to calculate the predictive risks of cardiovascular disease (CVD), coronary heart disease (CHD) and myocardial infarction (MI), and to identify the impact that simulated interventions may have.

    METHODS: Logistic regression analysis was used to distinguish associated current smoking characteristics. Five-year predictive risks of CVD, CHD and MI and the impact of simulated interventions were calculated utilizing the Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D) algorithm.

    RESULTS: Smoking status data were collected from 4274 participants and 1496 of these had sufficient data for simulated intervention calculations. Current smoking prevalence in these two groups was similar (23.2% vs. 19.9%, respectively). Characteristics associated with current smoking included age > 50 years compared with 30-39 years [odds ratio (OR) 0.65; 95% confidence interval (CI) 0.51-0.83], HIV exposure through injecting drug use compared with heterosexual exposure (OR 3.03; 95% CI 2.25-4.07), and receiving antiretroviral therapy (ART) at study sites in Singapore, South Korea, Malaysia, Japan and Vietnam in comparison to Thailand (all OR > 2). Women were less likely to smoke than men (OR 0.11; 95% CI 0.08-0.14). In simulated interventions, smoking cessation demonstrated the greatest impact in reducing CVD and CHD risk and closely approximated the impact of switching from abacavir to an alternate antiretroviral in the reduction of 5-year MI risk.

    CONCLUSIONS: Multiple interventions could reduce CVD, CHD and MI risk in Asian HIV-positive patients, with smoking cessation potentially being the most influential.

    MeSH terms: Adult; Asia/epidemiology; Cardiovascular Diseases/epidemiology*; Female; Humans; Male; Middle Aged; Smoking/adverse effects*; Smoking/epidemiology*; Cohort Studies; HIV Infections/complications*; Risk Assessment
  7. Noviendri D, Jaswir I, Taher M, Mohamed F, Salleh HM, Noorbatcha IA, et al.
    J Oleo Sci, 2016 Jul 15.
    PMID: 27430384
    Microencapsulation is a promising approach in drug delivery to protect the drug from degradation and allow controlled release of the drug in the body. Fucoxanthin-loaded microsphere (F-LM) was fabricated by two step w/o/w double emulsion solvent evaporation method with poly (L-lactic-co-glycolic acid) (PLGA) as carrier. The effect of four types of surfactants (PVA, Tween-20, Span-20 and SDS), homogenization speed, and concentration of PLGA polymer and surfactant (PVA), respectively, on particle size and morphology of F-LM were investigated. Among the surfactants tested, PVA showed the best results with smallest particle size (9.18 µm) and a smooth spherical surface. Increasing the homogenization speed resulted in a smaller mean F-LM particle size [d(0.50)] from 17.12 to 9.18 µm. Best particle size results and good morphology were attained at homogenization speed of 20 500 rpm. Meanwhile, increased PLGA concentration from 1.5 to 11.0 (% w/v) resulted in increased F-LM particle size. The mean particle size [d(0.5)] of F-LM increased from 3.93 to 11.88 µm. At 6.0 (% w/v) PLGA, F-LM showed the best structure and external morphology. Finally, increasing PVA concentration from 0.5 to 3.5 (% w/v) resulted in decreased particle size from 9.18 to 4.86 µm. Fucoxanthin characterization before and after microencapsulation was carried out to assess the success of the microencapsulation procedure. Thermo gravimetry analysis (TGA), glass transition (Tg) temperature of F-LM and fucoxanthin measured using DSC, ATR-FTIR and XRD indicated that fucoxanthin was successfully encapsulated into the PLGA matrix, while maintaining the structural and chemical integrity of fucoxanthin.
  8. O'Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, et al.
    Lancet, 2016 Aug 20;388(10046):761-75.
    PMID: 27431356 DOI: 10.1016/S0140-6736(16)30506-2
    BACKGROUND:Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke.
    METHODS:We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals.
    FINDINGS: Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001).
    INTERPRETATION: Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke.
    FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.
    MeSH terms: Adult; Africa/epidemiology; Aged; Alcohol Drinking/adverse effects; Alcohol Drinking/epidemiology; Apolipoproteins B/blood; Asia/epidemiology; Atrial Fibrillation/complications; Atrial Fibrillation/epidemiology; Australia/epidemiology; Cerebral Hemorrhage/blood; Cerebral Hemorrhage/complications; Cerebral Hemorrhage/epidemiology*; Brain Ischemia/blood; Brain Ischemia/complications; Brain Ischemia/epidemiology*; China/epidemiology; Europe/epidemiology; Feeding Behavior; Female; Humans; Hypertension/blood; Hypertension/complications*; Hypertension/epidemiology*; International Cooperation; Malaysia; Male; Middle Aged; Middle East/epidemiology; Motor Activity; Risk Factors; Smoking/adverse effects; Smoking/epidemiology; Biomarkers/blood; Health Behavior; Odds Ratio; Case-Control Studies; Apolipoprotein A-I/blood; Evidence-Based Medicine; Stroke/blood; Stroke/etiology; Stroke/epidemiology*; Stroke/pathology; Stroke/prevention & control*; Risk Reduction Behavior*; Diabetes Complications/epidemiology; Diabetes Complications/prevention & control; Waist-Hip Ratio; Obesity, Abdominal/complications; Obesity, Abdominal/epidemiology; Self Report
  9. Jin XY, Khan TM
    J Formos Med Assoc, 2016 Sep;115(9):689-702.
    PMID: 27431691 DOI: 10.1016/j.jfma.2016.05.006
    A systematic assessment of literature was done to estimate the impact of pruritus on health-related quality of life among patients with cholestatic liver disease (CLD). All the articles were reviewed manually for study design, population, outcomes, and study quality. A qualitative approach was used to analyze and extract data from included studies. A total of eight studies were retrieved, of which one was a cohort study and the other seven were cross-sectional studies. Overall, it appears that the incidence of pruritus was a common complication reported by most of the studies. Among patients with CLD incidence of pruritus was 29%. Pruritus was found to have a substantial impact on patients' health-related quality of life. Greater health-related quality of life impairment was observed with increased severity of pruritus. Pruritus was found to have a significant association (p<0.05) in quality-of-life instrument domains such as role limitation-physical, role limitation-emotional, bodily pain, vitality, energy, and physical mobility. Evidence suggests that pruritus has a substantial impact on health-related quality of life among patients with CLD. More research is required to support the evidence.
    MeSH terms: Cross-Sectional Studies; Humans; Liver Diseases; Pain; Plant Extracts; Pruritus; Quality of Life; Research Design; Cohort Studies; Incidence; Qualitative Research
  10. Chin VK, Atika Aziz NA, Hudu SA, Harmal NS, Syahrilnizam A, Jalilian FA, et al.
    J Virol Methods, 2016 10;236:117-125.
    PMID: 27432115 DOI: 10.1016/j.jviromet.2016.07.012
    Human respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection in infants and young children globally and is a significant pathogen of the elderly and immunocompromised. The M2-2 protein of respiratory syncytial virus (RSV) is particularly important in regulation of viral RNA transcription and replication that could be a potential anti-viral candidate against RSV infection. In this study, we designed and validated siRNAs that specifically target the RSV M2-2 gene. Four siRNAs targeting different regions of the M2-2 gene were designed using web tool. In-vitro evaluation of silencing effect was performed by using RSV infected Vero cell line. Viral M2-2 linked GFP recombinant plasmid was co-transfected with non-targeted siRNA, Pooled siRNA, siRNA 1, siRNA 2, siRNA 3 and siRNA 4 using synthetic cationic polymer. The silencing effect of M2-2 gene at the protein level was measured both qualitatively and quantitatively by using fluorescence microscopy and flow cytometry. Meanwhile, the silencing effect at the mRNA level was assessed by using RT-qPCR. This study showed that all four designed siRNAs can effectively and efficiently silence M2-2 gene. siRNA 2 showed the highest (98%) silencing effect on protein level and siRNA 4 with 83.1% at the mRNA level. The viral assay showed no significant cytopathic effects observed after 6days post-infection with siRNAs. In conclusion, this study showed the effectiveness of siRNA in silencing M2-2 gene both at the protein and mRNA level which could potentially be used as a novel therapeutic agent in the treatment of RSV infection. However, further study is warranted to investigate the silencing effect of M2-2 protein and inhibition of RSV infection.
    MeSH terms: Animals; Antiviral Agents/metabolism*; Cercopithecus aethiops; Flow Cytometry; Fluorometry; Recombinant Fusion Proteins/analysis; Recombinant Fusion Proteins/genetics; Vero Cells; Viral Proteins/antagonists & inhibitors*; Viral Proteins/genetics*; Virus Replication/drug effects*; Respiratory Syncytial Virus, Human/drug effects*; Respiratory Syncytial Virus, Human/physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA, Small Interfering/genetics*; RNA, Small Interfering/metabolism*; Green Fluorescent Proteins/analysis; Green Fluorescent Proteins/genetics; Real-Time Polymerase Chain Reaction
  11. Kar SP, Beesley J, Amin Al Olama A, Michailidou K, Tyrer J, Kote-Jarai Z, et al.
    Cancer Discov, 2016 Sep;6(9):1052-67.
    PMID: 27432226 DOI: 10.1158/2159-8290.CD-15-1227
    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis.

    SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

    MeSH terms: Breast Neoplasms/genetics*; Breast Neoplasms/metabolism; Chromosome Mapping; Enhancer Elements, Genetic; Female; Humans; Male; Organ Specificity/genetics; Ovarian Neoplasms/genetics*; Prostatic Neoplasms/genetics*; Prostatic Neoplasms/metabolism; Meta-Analysis as Topic; Signal Transduction; Case-Control Studies; Genetic Predisposition to Disease*; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Gene Regulatory Networks; Genome-Wide Association Study*; Genetic Loci*; Datasets as Topic
  12. Manshor NA, Wali Q, Wong KK, Muzakir SK, Fakharuddin A, Schmidt-Mende L, et al.
    Phys Chem Chem Phys, 2016 Aug 21;18(31):21629-39.
    PMID: 27432518 DOI: 10.1039/c6cp03600g
    Despite the high efficiency of over 21% reported for emerging thin film perovskite solar cells, one of the key issues prior to their commercial deployment is to attain their long term stability under ambient and outdoor conditions. The instability in perovskite is widely conceived to be humidity induced due to the water solubility of its initial precursors, which leads to decomposition of the perovskite crystal structure; however, we note that humidity alone is not the major degradation factor and it is rather the photon dose in combination with humidity exposure that triggers the instability. In our experiment, which is designed to decouple the effect of humidity and light on perovskite degradation, we investigate the shelf-lifetime of CH3NH3PbI3 films in the dark and under illumination under high humidity conditions (Rel. H. > 70%). We note minor degradation in perovskite films stored in a humid dark environment whereas upon exposure to light, the films undergo drastic degradation, primarily owing to the reactive TiO2/perovskite interface and also the surface defects of TiO2. To enhance its air-stability, we incorporate CH3NH3PbI3 perovskite in a polymer (poly-vinylpyrrolidone, PVP) matrix which retained its optical and structural characteristics in the dark for ∼2000 h and ∼800 h in room light soaking, significantly higher than a pristine perovskite film, which degraded completely in 600 h in the dark and in less than 100 h when exposed to light. We attribute the superior stability of PVP incorporated perovskite films to the improved structural stability of CH3NH3PbI3 and also to the improved TiO2/perovskite interface upon incorporating a polymer matrix. Charge injection from the polymer embedded perovskite films has also been confirmed by fabricating solar cells using them, thereby providing a promising future research pathway for stable and efficient perovskite solar cells.
  13. Kennedy KM, Flaherty GT
    J Travel Med, 2016 May;23(5).
    PMID: 27432905 DOI: 10.1093/jtm/taw048
    MeSH terms: Attitude of Health Personnel*; Humans; Malpractice/legislation & jurisprudence*; Professional-Patient Relations; Safety Management/legislation & jurisprudence; Medical Errors/prevention & control*; Professional Role*; Travel Medicine/legislation & jurisprudence*
  14. Kaur R, Kumar AC, Garg R, Sharma S, Rastogi T, Gupta VV
    Indian J Dent, 2016 Apr-Jun;7(2):66-9.
    PMID: 27433048 DOI: 10.4103/0975-962X.184644
    The impaction rate is higher for the third molars than for any other tooth in modern human population. This study was conducted with the aim to evaluate the validity of linear and angular measurements on the digital panoramic radiograph as a reference for early prediction of mandibular third molar eruption/impaction.
    MeSH terms: Humans; Molar; Molar, Third; Tooth Eruption; Tooth, Impacted
  15. Wei SC
    Intest Res, 2016 Jul;14(3):218-23.
    PMID: 27433143 DOI: 10.5217/ir.2016.14.3.218
    The cost of caring for patients with inflammatory bowel disease (IBD) is high. Without government support, the cost burden will unavoidably rest on the patients and their family. However, the government providing full support will place a large financial burden on the health-care systems of a country. The aim of this study is to understand the current status of public medical insurance systems in caring for IBD patients among Asian countries.
    MeSH terms: Asia; Delivery of Health Care; Patient Care; Government; Humans; Inflammatory Bowel Diseases
  16. Song HK, Lee KM, Jung SA, Hong SN, Han DS, Yang SK, et al.
    Intest Res, 2016 Jul;14(3):240-7.
    PMID: 27433146 DOI: 10.5217/ir.2016.14.3.240
    The quality of care in inflammatory bowel disease (IBD) has not been systematically estimated. The aim of this study was to investigate the current status of quality of IBD care in Asian countries.
    MeSH terms: Asia; Quality of Health Care; Inflammatory Bowel Diseases
  17. Ridzuan N, John CM, Sandrasaigaran P, Maqbool M, Liew LC, Lim J, et al.
    World J Diabetes, 2016 Jul 10;7(13):271-8.
    PMID: 27433296 DOI: 10.4239/wjd.v7.i13.271
    To assess the amount and pattern of reactive oxygen species (ROS) production in diabetic patient-derived neutrophils.
  18. Aziz J, Shezali H, Radzi Z, Yahya NA, Abu Kassim NH, Czernuszka J, et al.
    Skin Pharmacol Physiol, 2016;29(4):190-203.
    PMID: 27434176 DOI: 10.1159/000447017
    Collagen and elastin networks make up the majority of the extracellular matrix in many organs, such as the skin. The mechanisms which are involved in the maintenance of homeostatic equilibrium of these networks are numerous, involving the regulation of genetic expression, growth factor secretion, signalling pathways, secondary messaging systems, and ion channel activity. However, many factors are capable of disrupting these pathways, which leads to an imbalance of homeostatic equilibrium. Ultimately, this leads to changes in the physical nature of skin, both functionally and cosmetically. Although various factors have been identified, including carcinogenesis, ultraviolet exposure, and mechanical stretching of skin, it was discovered that many of them affect similar components of regulatory pathways, such as fibroblasts, lysyl oxidase, and fibronectin. Additionally, it was discovered that the various regulatory pathways intersect with each other at various stages instead of working independently of each other. This review paper proposes a model which elucidates how these molecular pathways intersect with one another, and how various internal and external factors can disrupt these pathways, ultimately leading to a disruption in collagen and elastin networks.
    MeSH terms: Animals; Biomechanical Phenomena/physiology; Collagen/metabolism*; Collagen/radiation effects; Collagen/ultrastructure*; Elastin/metabolism*; Elastin/radiation effects; Elastin/ultrastructure*; Environmental Exposure/adverse effects; Extracellular Matrix/metabolism; Extracellular Matrix/ultrastructure; Humans; Skin/metabolism*; Skin/pathology; Skin/ultrastructure; Signal Transduction/physiology; Oxidative Stress/physiology*
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