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Plexiform granular cell odontogenic tumor: unicystic variant

Siar CH, Ng KH, Jalil NA

Oral Surg. Oral Med. Oral Pathol., 1991 Jul;72(1):82-5.
PMID: 1891247

Plexiform granular cell odontogenic tumor of the mandible has recently been described. The cardinal histopathologic feature, as its name suggests, is a monophasic plexiform pattern of granular cells; the principal tumor in the differential diagnosis is granular cell ameloblastoma. Unlike the two previously reported cases of plexiform granular cell odontogenic tumor, which occurred as solid tumors in elderly men, the lesion reported here is a unicystic variant occurring in a middle-aged woman.
Fulltext Hybrid composite laminates reinforced with Kevlar/carbon/glass woven fabrics for ballistic impact testing

Randjbaran E, Zahari R, Jalil NA, Majid DL

ScientificWorldJournal, 2014;2014:413753.
PMID: 24955400 DOI: 10.1155/2014/413753

Current study reported a facile method to investigate the effects of stacking sequence layers of hybrid composite materials on ballistic energy absorption by running the ballistic test at the high velocity ballistic impact conditions. The velocity and absorbed energy were accordingly calculated as well. The specimens were fabricated from Kevlar, carbon, and glass woven fabrics and resin and were experimentally investigated under impact conditions. All the specimens possessed equal mass, shape, and density; nevertheless, the layers were ordered in different stacking sequence. After running the ballistic test at the same conditions, the final velocities of the cylindrical AISI 4340 Steel pellet showed how much energy was absorbed by the samples. The energy absorption of each sample through the ballistic impact was calculated; accordingly, the proper ballistic impact resistance materials could be found by conducting the test. This paper can be further studied in order to characterise the material properties for the different layers.
Fulltext Prevalence of cancers of female organs among patients with diabetes type 2 in Kelantan, Malaysia: Observations over an 11 year period and strategies to reduce the incidence

Jalil NA, Zin AA, Othman NH

Asian Pac J Cancer Prev, 2015;16(16):7267-70.
PMID: 26514522

INTRODUCTION: Kelantan is one of the states in Malaysia which has a high prevalence of type 2 diabetes (DM2). Other than with endometrial carcinoma, the association of DM2 with particular female cancers is not known.
OBJECTIVE: To determine the proportion of breast, cervical, ovarian and endometrial cancers among females with DM2 diagnosed in Hospital Universiti Sains Malaysia (HUSM) over an 11 year period.
MATERIALS AND METHODS: All histologically confirmed cases of breast, endometrial, cervical and ovarian carcinomas admitted to the Hospital were included in the study. The patient diabetic status was traced from the hospital medical records.
RESULTS: There was a total of 860 cases of breast, cervical, ovarian and endometrial carcinomas over this period. Breast carcinoma was the commonest, accounting for 437/860 (50.8%) followed by cervix, 159/860 (18.5%), ovarian, 143/860 (16.6%) and endometrial carcinomas, 121/860 (14.1%). Out of these, 228/860 (26.5%) were confirmed diabetics. Endometrial carcinoma patients showed the highest proportion being diabetics, 42.1% (51/121), followed by ovarian cancer, 25.9% (37/143), breast carcinoma, 23.6% (103/437) and cervical cancer 23.3% (37/159).
CONCLUSIONS: There is a significant proportion of DM2 among women with these four cancers, endometrial carcinoma being the highest followed by ovarian, breast and cervical carcinoma. The rising trend of these four cancers is in tandem with an increasing trend of DM2 in the community. In populations where diabetes is prevalent, screening for epithelial cancers should be rigourous. Diabetic clinics should include screening for these cancers among their female patients and gynecology clinics should screen the women they treat for their diabetes status.
Relapse of B-cell acute lymphoblastic leukaemia presenting as right aural polyp with facial and mandibular nerves palsy

Shiun Chuen C, Md Daud MK, Che Jalil NA, Hazmi H

Med J Malaysia, 2017 10;72(5):318-320.
PMID: 29197892 MyJurnal

A patient presenting with an ear polyp is a common finding in otorhinolaryngology practice. The common causes include chronic otitis media and cholesteatoma. We report an adult female patient with a history of acute leukaemia presenting with chronic otitis media symptoms and right ear polyp. She was subsequently diagnosed as relapse of B-cell acute lymphoblastic leukaemia based on histopathological examination. The presentation may be similar to an inflammatory pathology of the middle ear, making it misleading.
Fulltext Partial mtDNA sequencing data of vulnerable Cephalopachus bancanus from the Malaysian Borneo

Zahidin MA, Jalil NA, Naharuddin NM, Abd Rahman MR, Gani M, Abdullah MT

Data Brief, 2019 Aug;25:104133.
PMID: 31321260 DOI: 10.1016/j.dib.2019.104133

Tarsier is an endangered nocturnal primate in the family Tarsiidae and is an endemic to Sundaic islands of Philippine (Carlito syrichta), Sulawesi (Tarsius tarsier-complex) and Borneo (Cephalopachus bancanus). Recent records indicated that most molecular studies were done on the Eastern Tarsier and little information for the other group of tarsiers. Here, we present a partial cytochrome b data set of C. bancanus in Sarawak, Malaysian Borneo. Standard mist nets were deployed at strategic locations in various habitat types. A total of 18 individuals were caught, measured and weighed. Approximately, 2 × 2 mm of tissue samples were taken and preserved in molecular grade alcohol. Out of 18, only 11 samples were screened with partial mtDNA (cytochrome b) and the DNA sequences were registered in the GenBank (accession numbers: KY794797-KY794807). Phylogenetic trees were constructed with 20 additional mtDNA sequences downloaded from GenBank. The data are valuable for the management authorities to regulate the type of management units for the metapopulation to sustain population genetics integrity of tarsiers in the range countries across the Sunda Shelf.
Expression of IGFBP-rP1 in ovarian and breast cancers in association with diabetes mellitus status

Mohd Nafi SN, Siti Azrin AH, Mat Zin AA, Othman NH, Che Jalil NA

Malays J Pathol, 2019 Apr;41(1):33-39.
PMID: 31025635

INTRODUCTION: Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is an important component of the IGF system that regulates insulin resistance-related to tumour development. The aim of this study is to investigate the expression of IGFBP-rP1 among female cancer patients who are known or not known to have Type 2 Diabetes Mellitus (T2DM).
MATERIALS AND METHODS: Using a cross-sectional design, cases of ovarian and breast cancer with clinical status of T2DM were selected over a 10-year period in Hospital Universiti Sains Malaysia. Immunohistochemical staining for IGFBP-rP1 was performed on paraffin-embedded tissues and the results were correlated with the patient's demographic and clinicopathological data.
RESULTS: A total of 152 breast cancer patients were recruited into the current study with 33.5% (51/152) patients were positive T2DM. Most of the breast cancer patients with T2DM were IGFBP-rP1-negative (66.7%, 34/51). The IGFBP-rP1 expression was significantly difference between breast cancer subjects with and without T2DM (p<0.001). There was no significant association of IGFBP-rP1 expression with data on the demographic and clinicopathological profiles of patients with breast cancer. Meanwhile, positive IGFBP-rP1 expression was evident in 44 out of 108 (40.74%) ovarian cancer cases. Among these cases, 36 were T2DM. In contrast to breast cancer cases, IGFBP-rP1 was mostly expressed among ovarian cancer patients with T2DM (66.7%, 24/36, p < 0.001). However, the -positive expression was not significantly associated with any sociodemographic and clinicopathological features of ovarian cancers.
CONCLUSIONS: Majority of breast cancer patients with T2DM did not express IGFBP-rP1. In contrast, majority of the ovarian cancer patients with T2DM expressed IGFBP-rP1.
Metastatic leiomyosarcoma of the thyroid: A rare entity

Che Jalil NA, Rama Chandran P, Samsudin AHZ, Yahya MM, Wan Abdul Rahman WF

Malays J Pathol, 2021 Apr;43(1):69-73.
PMID: 33903308

Cancer metastasis to the thyroid gland from non-thyroid sites is a rare presentation in clinical practice. The most frequent primary cancers that metastasise to the thyroid are renal cell carcinoma, followed by colorectal, lung and breast. We report a case of a 64-year-old Malay lady who presented with anterior neck swelling 4 years after an initial diagnosis of uterine leiomyosarcoma. She had undergone a hysterectomy procedure four years ago. Fine needle aspiration cytology of the thyroid mass suggested undifferentiated thyroid carcinoma. After multi-disciplinary discussion, the patient underwent thyroidectomy and the final histopathological diagnosis was metastatic leiomyosarcoma of the thyroid. The diagnosis was aided by an immunohistochemistry panel of positive myogenic markers, negative epithelial markers as well as the previous medical history of uterine leiomyosarcoma. Metastatic leiomyosarcoma of the thyroid may mimic primary undifferentiated (anaplastic) thyroid carcinoma (UTC) with a sarcomatoid pattern, medullary thyroid carcinoma (MTC) with spindle cells morphology and spindle cell tumour with thymus-like differentiation (SETTLE). Hence, a multidisciplinary approach must be practised by pathologists, surgeons and radiologists to consider metastatic lesions of the thyroid gland, especially when a previous history of cancer exists or is suspected.
Heterotopic pancreatitis complicated with septic shock: An unusual presentation

Rahman WF, Jalil NA, Samsudin H, Merican SR, Lam AK

Pathology, 2016 Feb;48 Suppl 1:S160.
PMID: 27772966 DOI: 10.1016/j.pathol.2015.12.439
Endometrial Cancer in Hospital Universiti Sains Malaysia

Wan-Nor-Asyikeen WA, Siti-Azrin AH, Jalil NA, Othman NH, Zain AA

Asian Pac J Cancer Prev, 2016;17(6):2867-70.
PMID: 27356704

BACKGROUND: Endometrial cancer is the most common gynecological malignancy among females worldwide, approximately 320,000 women being diagnosed with the disease each year and 76,000 dying. To date, there is limited knowledge of endometrial cancer in Malaysia.
OBJECTIVES: To identify the epidemiological profile and prognostic factors of survival.
MATERIALS AND METHODS: A list of endometrial cancer patients in 2000-2011 was obtained from the hospital Record Department. Only cases confirmed by histopathology examination were included. We excluded those with incomplete medical records or referral cases. Simple and multiple Cox regression approaches were used for data analysis.
RESULTS: Only 108 cases were included with a mean (SD) age of 62.7 (12.3) years, with 87.0% Malay ethnicity. Grade of cancer was: 29.1% grade 1, 43.7% grade 2 and 27.2% grade 3. The majority of patients had non-endometrioid type (60.2%), with myometrial invasion (82.2%) and lymphovascular invasion (57.3%). The significant prognostic factors were age (HR 1.05; 95% CI: 1.02, 1.08, p=0.002) and having lymphovascular invasion (HR 2.15; 95% CI: 1.08, 4.29; p=0.030).
CONCLUSIONS: Endometrial cancer patients should be diagnosed earlier to reduce the risk of mortality. The public should be given education on the signs and symptoms of the disease.
Fulltext Hepatoprotective Effect of Bee Bread in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Rats: Impact on Oxidative Stress and Inflammation

Zakaria Z, Othman ZA, Suleiman JB, Che Jalil NA, Ghazali WSW, Nna VU, et al.

Antioxidants (Basel), 2021 Dec 20;10(12).
PMID: 34943134 DOI: 10.3390/antiox10122031

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a pathological accumulation of hepatic lipid closely linked with many metabolic disorders, oxidative stress and inflammation. We aimed to evaluate the hepatoprotective effect of bee bread on oxidative stress and inflammatory parameters in MAFLD rats. Twenty-eight male Sprague-Dawley rats were assigned into four groups (n = 7/group): normal control (NC), high-fat diet (HFD), bee bread (HFD + Bb, HFD + 0.5 g/kg/day bee bread) and orlistat (HFD + Or, HFD + 10 mg/kg/day orlistat) groups. After 12 weeks, the HFD group demonstrated significantly higher body weight gain, serum levels of lipids (TG, TC, LDL), liver enzymes (AST, ALT, ALP) and adiponectin, liver lipids (TG, TC) and insulin resistance (HOMA-IR). Furthermore, the HFD group showed significantly decreased antioxidant enzyme activities (GPx, GST, GR, SOD, CAT) and GSH level, and increased liver oxidative stress (TBARS, NO), translocation of Nrf2 to the nucleus, Keap1 expression and inflammation (TNF-α, NF-κβ, MCP-1) together with histopathological alterations (steatosis, hepatocyte hypertrophy, inflammatory cell infiltration, collagen deposition), which indicated the presence of non-alcoholic steatohepatitis (NASH) and fibrosis. Bee bread significantly attenuated all these changes exerted by HFD feeding. In conclusion, our results suggest that bee bread might have antioxidant, anti-inflammatory, anti-steatotic and anti-fibrotic effects that are beneficial in protecting liver progression towards NASH and fibrosis.
Fulltext Therapeutic Potential of Honey and Propolis on Ocular Disease

Abd Rashid N, Mohammed SNF, Syed Abd Halim SA, Ghafar NA, Abdul Jalil NA

Pharmaceuticals (Basel), 2022 Nov 17;15(11).
PMID: 36422549 DOI: 10.3390/ph15111419

Honey and propolis have recently become the key target of attention for treating certain diseases and promoting overall health and well-being. A high content of flavonoids and phenolic acids found in both honey and propolis contributes to the antioxidant properties to scavenge free radicals. Honey and propolis also exhibited antibacterial effects where they act in two ways, namely the production of hydrogen peroxide (H2O2) and gluconic acids following the enzymatic activities of glucose oxidase, which exerts oxidative damage on the bacteria. Additionally, the anti-inflammatory effects of honey and propolis are mainly by reducing proinflammatory factors such as interleukins and tumor necrosis factor alpha (TNF-α). Their effects on pain were discovered through modulation at a peripheral nociceptive neuron or binding to an opioid receptor in the higher center. The aforementioned properties of honey have been reported to possess potential therapeutic topical application on the exterior parts of the eyes, particularly in treating conjunctivitis, keratitis, blepharitis, and corneal injury. In contrast, most of the medicinal values of propolis are beneficial in the internal ocular area, such as the retina, optic nerve, and uvea. This review aims to update the current discoveries of honey and propolis in treating various ocular diseases, including their antioxidant, anti-inflammatory, antibacterial, and anti-nociceptive properties. In conclusion, research has shown that propolis and honey have considerable therapeutic promise for treating various eye illnesses, although the present study designs are primarily animal and in vitro studies. Therefore, there is an urgent need to translate this finding into a clinical setting.
Bee bread attenuates the progression of atherosclerosis by activating Nrf2/Keap1 and modulating TNF-α/NF-κβ-associated mast cell migration and a mitochondrial-dependent apoptotic pathway in the obese rat model

Othman ZA, Zakaria Z, Suleiman JB, Che Jalil NA, Wan Ghazali WS, Mohamed M

Food Funct, 2022 Aug 01;13(15):8119-8130.
PMID: 35796099 DOI: 10.1039/d2fo00949h

This study explores the anti-atherosclerotic effects of bee bread in the context of oxidative stress, inflammation, and apoptosis phenomena in an obesity animal model, and its vitamin composition. Forty male Sprague-Dawley rats were administered with a normal diet (Normal group) and a high-fat diet (HFD) to induce obesity. After 6 weeks, obese rats that received the HFD were treated either with distilled water (Ob group), bee bread at 0.5 g per kg per day (Ob + Bb group), or orlistat at 10 mg per kg per day (Ob + Or group) concomitant with the HFD for another 6 weeks. Bee bread significantly improved atherosclerotic changes by enhancing the immunoexpressions of Nrf2/Keap1, impeding the immunoexpressions of NF-κβ downstream proteins, and intensifying Bcl-2 upregulation, attributed to the improvement in mast cell adherence and collagen deposition in the aortic wall of the Ob + Bb group. We have demonstrated that the treatment with bee bread attenuates the progression of atherosclerosis through its inhibition of vascular oxidative stress, and retardation of inflammatory reaction and apoptosis in obese rats, indicating its potential therapeutic targets for obesity-related vascular diseases. This could be partly attributed to the components of vitamins such as vitamins A, C and E that are present in bee bread, which need further study for the exact molecular mechanism of action.
Fulltext KRAS Mutational Profiles among Colorectal Cancer Patients in the East Coast of Peninsular Malaysia

Hasbullah HH, Sulong S, Che Jalil NA, Abdul Aziz AA, Musa N, Musa M

Diagnostics (Basel), 2023 Feb 21;13(5).
PMID: 36899966 DOI: 10.3390/diagnostics13050822

BACKGROUND: KRAS is a key driver gene in colorectal carcinogenesis. Despite this, there are still limited data on the mutational status of KRAS amongst colorectal cancer (CRC) patients in Malaysia. In the present study, we aimed to analyze the KRAS mutational profiles on codons 12 and 13 amongst CRC patients in Hospital Universiti Sains Malaysia, Kelantan, located on the East Coast of Peninsular Malaysia.
METHODS: DNA were extracted from formalin-fixed, paraffin-embedded tissues obtained from 33 CRC patients diagnosed between 2018 and 2019. Amplifications of codons 12 and 13 of KRAS were conducted using conventional polymerase chain reaction (PCR) followed by Sanger sequencing.
RESULTS: Mutations were identified in 36.4% (12/33) of patients, with G12D (50%) being the most frequent single-point mutation observed, followed by G12V (25%), G13D (16.7%), and G12S (8.3%). No correlation was found between mutant KRAS and location of the tumor, staging, and initial carcinoembryonic antigen (CEA) level.
CONCLUSION: Current analyses revealed that a significant proportion of CRC patients in the East Coast of Peninsular Malaysia have KRAS mutations, where this frequency is higher compared to those in the West Coast. The findings of this study would serve as a precursor for further research that explores KRAS mutational status and the profiling of other candidate genes among Malaysian CRC patients.
Fulltext Essential Oils in Cervical Cancer: Narrative Review on Current Insights and Future Prospects

Abd Rashid N, Mohamad Najib NH, Abdul Jalil NA, Teoh SL

Antioxidants (Basel), 2023 Dec 13;12(12).
PMID: 38136228 DOI: 10.3390/antiox12122109

Cervical cancer is a prevalent and often devastating disease affecting women worldwide. Traditional treatment modalities such as surgery, chemotherapy, and radiation therapy have significantly improved survival rates, but they are often accompanied by side effects and challenges that can impact a patient's quality of life. In recent years, the integration of essential oils into the management of cervical cancer has gained attention. This review provides an in-depth exploration of the role of various essential oils in cervical cancer, offering insights into their potential benefits and the existing body of research. The review also delves into future directions and challenges in this emerging field, emphasizing promising research areas and advanced delivery systems. The encapsulation of essential oils with solid lipid nanoparticles, nanoemulsification of essential oils, or the combination of essential oils with conventional treatments showed promising results by increasing the anticancer properties of essential oils. As the use of essential oils in cervical cancer treatment or management evolves, this review aims to provide a comprehensive perspective, balancing the potential of these natural remedies with the challenges and considerations that need to be addressed.
Estimating natural frequency of pipe with various geometries: Improvement of frequency factors

Saari NF, Putra A, Irianto, Dan RM, Zeli MA, Ramlan R, et al.

Heliyon, 2024 Feb 29;10(4):e26148.
PMID: 38390043 DOI: 10.1016/j.heliyon.2024.e26148

Piping system is the main structure in many industrial applications, especially for large industry relating with processing and transporting fluids, such as oil and gas industries. The fluid-induced vibration is often the cause of structural fatigue in pipes and therefore piping vibration need to be closely monitored. In case of high piping vibration, knowledge of the natural frequency of a pipe section is crucial for an engineer to propose the right troubleshoot action, either for a temporary or even for a long-term solution for the piping vibration. Therefore, prediction of the pipe natural frequency using a simple formulae is thus of interest, without dealing with complex numerical simulation using a commercial software which consumes cost and time. In this paper, the vibration mode shapes of various possible geometries of pipes in practice were simulated in ANSYS and the simulated natural frequency is related to a natural frequency of an Euler-Bernoulli beam using a correction factor for each corresponding piping geometry. This paper extends the previous work by allowing the boundary conditions of the pipe ends to be simply supported, in addition to the clamped edges. In this way, the frequency factor charts are presented in the range of possible correction factor values to accommodate the real conditions of pipe arrangement in practical application. An experiment from a case study to verify the proposed method is also presented.
Fulltext Median Survival Time of Endometrial Cancer Patients with Lymphovascular Invasion at the Hospital Universiti Sains Malaysia

Asyikeen WA, Siti-Azrin AH, Jalil NA, Zin AA, Othman NH

Malays J Med Sci, 2016 Nov;23(6):44-51.
PMID: 28090178 MyJurnal DOI: 10.21315/mjms2016.23.6.5

Endometrial cancer is the most common gynaecologic malignancy among females worldwide. The purpose of this study was to determine the median survival time of endometrial cancer patients at the Hospital Universiti Sains Malaysia (USM).
INFLUENZA VACCINATION UPTAKE AMONG HEALTHCARE WORKERS AT A MALAYSIAN TEACHING HOSPITAL

Rashid ZZ, Jasme H, Liang HJ, Yusof MM, Sharani ZZ, Mohamad M, et al.

Southeast Asian J. Trop. Med. Public Health, 2015 Mar;46(2):215-25.
PMID: 26513924

Annual influenza vaccination is the most important preventive strategy against influenza illness in healthcare workers (HCWs), who could acquire influenza from and transmit influenza to patients and other HCWs. Despite the well established benefits and strong recommendations for influenza vaccination for all HCWs, influenza vaccination uptake at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) for the past 3 years has been low and is decreasing. We aimed to determine the factors associated with influenza vaccination uptake among HCWs at UKMMC. We conducted a cross sectional study via questionnaire among 211 randomly selected HCWs, consisting of 106 HCWs who were vaccinated in 2011 and 105 HCWs who were not vaccinated in 2010 or 2011. We had a 100% response rate. Influenza vaccination uptake was significantly associated with age and previous vaccination history, with older HCWs being more likely to be vaccinated (adjusted OR = 12.494; 95% CI:6.278-24.863; p < 0.001) and HCWs with previous vaccination history being more likely to be vaccinated (adjusted OR = 1.038; 95% CI:1.001-1.077; p = 0.045). Influenza vaccination uptake was not associated with gender (p = 0.926) or job category (p = 0.220). Publicity at the workplace was the main source of information about the vaccine (51.2% of respondents), followed by colleagues (29.9%). Despite the low uptake, 85.3% of respondents believed influenza vaccination was important for disease prevention. The most common reason given for vaccination was protection against influenza infection (73.6%). The most common reason for not having the vaccine was time constraints (56.2%). An evidenced-based strategy needs to be developed to improve vaccine uptake or having mandatory vaccination.
Fulltext The role of natural antioxidants in cisplatin-induced hepatotoxicity

Abd Rashid N, Abd Halim SAS, Teoh SL, Budin SB, Hussan F, Adib Ridzuan NR, et al.

Biomed Pharmacother, 2021 Dec;144:112328.
PMID: 34653753 DOI: 10.1016/j.biopha.2021.112328

Cisplatin is a potent platinum-based anticancer drug approved by the Food Drug Administration (FDA) in 1978. Despite its advantages against solid tumors, cisplatin confers toxicity to various tissues that limit its clinical uses. In cisplatin-induced hepatotoxicity, few mechanisms have been identified, which started as excess generation of reactive oxygen species that leads to oxidative stress, inflammation, DNA damage and apoptosis in the liver. Various natural products, plant extracts and oil rich in flavonoids, terpenoids, polyphenols, and phenolic acids were able to minimize oxidative stress by restoring the level of antioxidant enzymes and acting as an anti-inflammatory agent. Likewise, treatment with honey and royal jelly was demonstrated to decrease serum transaminases and scavenge free radicals in the liver after cisplatin administration. Medicinal properties of these natural products have a promising potential as a complementary therapy to counteract cisplatin-induced hepatotoxicity. This review concentrated on the protective role of several natural products, which has been proven in the laboratory findings to combat cisplatin-induced hepatotoxicity.
Fulltext Identification of AOC3 and LRRC17 as Colonic Fibroblast Activation Markers and Their Potential Roles in Colorectal Cancer Progression

Ahmad Zawawi SS, Mohd Azram NAS, Sulong S, Zakaria AD, Lee YY, Che Jalil NA, et al.

Asian Pac J Cancer Prev, 2023 Sep 01;24(9):3099-3107.
PMID: 37774061 DOI: 10.31557/APJCP.2023.24.9.3099

BACKGROUND: Accumulation of cancer-associated fibroblasts (CAFs) in the tumor stroma is linked to poor prognosis in colorectal cancer (CRC). CAF-cancer cell interplay, facilitated by secretomes including transforming growth factor-beta 1 (TGF-β1), supports fibroblast activation, drives colorectal carcinogenesis, and contributes to CRC aggressive phenotypes. Although widely used, traditional CAF biomarkers are found to have heterogeneous and non-specific expression. Amine oxidase copper containing 3 (AOC3) and leucine-rich repeat-containing 17 (LRRC17) have been reported to be emerging markers of myofibroblasts.
AIM: Our objective was to investigate the potential of AOC3 and LRRC17 as biomarkers for fibroblast activation thus predicting their roles in CRC progression.
METHODS: Immunofluorescence (IF) staining of AOC3 and LRRC17 was performed on myofibroblast line (CCD-112CoN), primary fibroblasts from colorectal tumor (CAFs), and adjacent normal tissue (normal fibroblasts-NFs). SW620 (epithelial CRC cell line) was used as a control. Conventional CAF biomarker (alpha-smooth muscle actin - α-SMA) was included in the IF analysis. Fluorescence intensity was compared between groups using ImageJ software. Proliferation and contractility of treated cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and collagen gel contraction assays, respectively. Fibroblast contraction under TGF-β1 treatment was compared to those treated with complete medium (addition of 10% serum) and serum free (SF) medium.
RESULTS: Positive AOC3, LRRC17, and α-SMA expression were observed in colonic fibroblasts, more prominent in CAFs, whereas negative staining was found in SW620. Significant downregulation of AOC3, and upregulations in LRRC17 and α-SMA expression was found in TGF-β1-treated fibroblasts compared to SF medium treatment (p-value<0.05). All fibroblasts exhibited higher proliferation in complete medium and under treatment with conditioned medium from SW620 than SF medium. Significant contraction of NFs was recorded in complete medium and TGF-β1 (p-value<0.01).
CONCLUSION: Our results demonstrate AOC3 and LRRC17 as the potential markers of CAF activation which promote CRC progression.
Polygonum minus essential oil modulates cisplatin-induced hepatotoxicity through inflammatory and apoptotic pathways

Abd Rashid N, Hussan F, Hamid A, Adib Ridzuan NR, Halim SASA, Abdul Jalil NA, et al.

EXCLI J, 2020;19:1246-1265.
PMID: 33122975 DOI: 10.17179/excli2020-2355

Oxidative stress, inflammation and apoptosis are thought as primary mediators of cisplatin-induced hepatotoxicity. The objective of this study was to determine the protective effect of Polygonum minus essential oil in cisplatin-induced hepatotoxicity. A total of forty-two male rats were randomly divided into seven groups: control, cisplatin, β-caryophyllene 150 mg/kg (BCP), PmEO 100 mg/kg + cisplatin (PmEO100CP), PmEO 200 mg/kg + cisplatin (PmEO200CP), PmEO 400 mg/kg + cisplatin (PmEO400CP) and PmEO 400 mg/kg (PmEO400). Rats in the BCP, PmEO100CP, PmEO200CP, PmEO400CP and PmEO400 group received respective treatment orally for 14 consecutive days prior to cisplatin injection. All animals except for those in the control group and PmEO400 were administered with a single dose of cisplatin (10 mg/kg) intraperitoneally on day 15 and all animals were sacrificed on day 18. PmEO100CP pretreatment protected against cisplatin-induced hepatotoxicity by decreasing CYP2E1 and indicators of oxidative stress including malondialdehyde, 8-OHdG and protein carbonyl which was accompanied by increased antioxidant status (glutathione, glutathione peroxidase, superoxide dismutase and catalase) as compared to cisplatin group. PmEO100CP pretreatment also modulated changes in liver inflammatory markers (TNF-α, IL-1α, IL-1β, IL-6 and IL-10). PmEO100CP administration also notably reduced cisplatin-induced apoptosis significantly as compared to cisplatin group. In conclusion, our results suggested that P. minus essential oil at a dose of 100 mg/kg may protect against cisplatin-induced hepatotoxicity possibly via inhibition of oxidative stress, inflammation and apoptosis.

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