MyMedR

Displaying publications 21 - 40 of 172 in total

Abstract:

Sort:

Fulltext Corticosteroid Therapy in Optic Neuropathy Secondary to Nasopharyngeal Carcinoma

Wahab Z, Tai E, Wan Hitam WH, Sonny Teo KS

Cureus, 2021 Mar 06;13(3):e13735.
PMID: 33842113 DOI: 10.7759/cureus.13735

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells of the nasopharynx. NPC can spread and invade the base of skull, nasal cavity, paranasal sinuses, pterygopalatine fossa, and apex of the orbit. However, the involvement of the optic nerve in NPC is rare. The purpose of this case report is to report the efficacy of corticosteroid therapy in optic neuropathy secondary to NPC.
CLINICAL CASE: A 56-year-old Chinese woman, an active smoker, presented with a hearing deficit, persistent tinnitus and nasal congestion. Examination and investigations revealed the presence of a mass in the nasopharynx. Tissue biopsy revealed nasopharyngeal carcinoma. However, the Epstein-Barr virus was not tested. She was counseled for chemotherapy, but refused and was subsequently lost to follow up. She presented one year later with right eye ptosis associated with progressive worsening of diplopia and blurring of vision. Examination revealed multiple (second, third, fourth and sixth) cranial nerve involvement. Systemic examination and investigations revealed cervical lymphadenopathy and liver metastasis. Repeated imaging showed that the mass had invaded the base of the skull, cavernous sinus and orbital apices. Pulse dosing of corticosteroid therapy was commenced, resulting in dramatic improvement of vision.
CONCLUSION: Optic neuropathy may be the presenting sign of NPC. Corticosteroid therapy can offer immediate visual improvement.

Matched MeSH terms: Epithelial Cells
Rutin-loaded liquid crystalline nanoparticles attenuate oxidative stress in bronchial epithelial cells: a PCR validation

Mehta M, Paudel KR, Shukla SD, Shastri MD, Satija S, Singh SK, et al.

Future Med Chem, 2021 03;13(6):543-549.
PMID: 33538615 DOI: 10.4155/fmc-2020-0297

Aim: In the present study, the inhibitory potential of rutin-loaded liquid crystalline nanoparticles (LCNs) on oxidative stress was determined in human bronchial epithelial cells (BEAS-2B) by analysing the expression levels of different antioxidant (NADPH quinine oxidoreductase-1 (NQO1); γ-glutamyl cysteine synthetase catalytic subunit (GCLC)) and pro-oxidant (NADPH oxidase (Nox)-4; Nox2B) genes. Results: Our findings revealed that the rutin-loaded LCNs inhibited the genes, namely Nox2B and Nox4, which caused oxidative stress. In addition, these nanoparticles demonstrated an upregulation in the expression of the antioxidant genes Gclc and Nqo-1 in a dose-dependent manner. Conclusion: The study indicates the promising potential of rutin-loaded LCNs as an effective treatment strategy in patients with high oxidant loads in various respiratory diseases.

Matched MeSH terms: Epithelial Cells/cytology; Epithelial Cells/drug effects; Epithelial Cells/metabolism
Experience in managing glaucoma filtration surgery complications with oral doxycycline: A case series

Yong GY, Mohamed-Noor J, Ong PY, Suliman NB, Lim CW, Zahari M

Eur J Ophthalmol, 2021 Feb 07.
PMID: 33550831 DOI: 10.1177/1120672121992953

PURPOSE: To report the clinical profile and effectiveness of oral doxycycline as a non-invasive treatment for glaucoma filtering surgery complications.
METHOD: Prospective case series.
RESULTS: Doxycycline is widely used in treating corneal melts, ocular surface diseases, meibomian gland disease, recurrent epithelial cell erosion, rosacea, and keratitis sicca. This prospective case series highlights the successful treatment of five patients with leaking blebs and conjunctiva erosion from glaucoma filtration surgery with the use of oral doxycycline. There was no adverse event reported in our cases.
CONCLUSIONS: This study suggests that oral doxycycline may be a feasible non-surgical treatment modality due to its ability to inhibit collagenolysis, restore the Meibomian gland function, thereby stopping breakdown and promote conjunctival tissue healing.

Matched MeSH terms: Epithelial Cells
Fulltext Reduced occludin and claudin-7 expression is associated with urban locations and exposure to second-hand smoke in allergic rhinitis patients

Nur Husna SM, Siti Sarah CO, Tan HT, Md Shukri N, Mohd Ashari NS, Wong KK

Sci Rep, 2021 01 13;11(1):1245.
PMID: 33441633 DOI: 10.1038/s41598-020-79208-y

The breakdown of nasal epithelial barrier occurs in allergic rhinitis (AR) patients. Impairment of cell junction molecules including tight junctions (TJs) and desmosomes plays causative roles in the pathogenesis of AR. In this study, we investigated the transcript expression levels of TJs including occludin (OCLN), claudin-3 and -7 (CLDN3 and CLDN7), desmoglein 3 (DSG3) and thymic stromal lymphopoietin (TSLP) in AR patients (n = 30) and non-allergic controls (n = 30). Nasal epithelial cells of non-allergic controls and AR patients were collected to examine their mRNA expression levels, and to correlate with clinico-demographical and environmental parameters. We demonstrated that the expression of OCLN (p = 0.009), CLDN3 (p = 0.032) or CLDN7 (p = 0.004) transcript was significantly lower in AR patients compared with non-allergic controls. No significant difference was observed in the expression of DSG3 (p = 0.750) or TSLP (p = 0.991) transcript in AR patients compared with non-allergic controls. A significant association between urban locations and lower OCLN expression (p = 0.010), or exposure to second-hand smoke with lower CLDN7 expression (p = 0.042) was found in AR patients. Interestingly, none of the TJs expression was significantly associated with having pets, frequency of changing bedsheet and housekeeping. These results suggest that defective nasal epithelial barrier in AR patients is attributable to reduced expression of OCLN and CLDN7 associated with urban locations and exposure to second-hand smoke, supporting recent findings that air pollution represents one of the causes of AR.

Matched MeSH terms: Epithelial Cells/metabolism*; Epithelial Cells/pathology
Fulltext Pharmacological Evaluation of Safoof-e-Pathar Phori- A Polyherbal Unani Formulation for Urolithiasis

Ahmad W, Khan MA, Ashraf K, Ahmad A, Daud Ali M, Ansari MN, et al.

Front Pharmacol, 2021;12:597990.
PMID: 33935697 DOI: 10.3389/fphar.2021.597990

Safoof-e-Pathar phori (SPP) is an Unani poly-herbomineral formulation, which has for a long time been used as a medicine due to its antiurolithiatic activity, as per the Unani Pharmacopoeia. This powder formulation is prepared using six different plant/mineral constituents. In this study, we explored the antiurolithiatic and antioxidant potentials of SPP (at 700 and 1,000 mg/kg) in albino Wistar rats with urolithiasis induced by 0.75% ethylene glycol (EG) and 1% ammonium chloride (AC). Long-term oral toxicity studies were performed according to the Organization for Economic Co-operation and Development (OECD) guidelines for 90 days at an oral dose of 700 mg/kg of SPP. The EG urolithiatic toxicant group had significantly higher levels of urinary calcium, serum creatinine, blood urea, and tissue lipid peroxidation and significantly (p < 0.001 vs control) lower levels of urinary sodium and potassium than the normal control group. Histopathological examination revealed the presence of refractile crystals in the tubular epithelial cell and damage to proximal tubular epithelium in the toxicant group but not in the SPP treatment groups. Treatment of SPP at 700 and 1,000 mg/kg significantly (p < 0.001 vs toxicant) lowered urinary calcium, serum creatinine, blood urea, and lipid peroxidation in urolithiatic rats, 21 days after induction of urolithiasis compared to the toxicant group. A long-term oral toxicity study revealed the normal growth of animals without any significant change in hematological, hepatic, and renal parameters; there was no evidence of abnormal histology of the heart, kidney, liver, spleen, or stomach tissues. These results suggest the usefulness of SPP as an antiurolithiatic and an antioxidant agent, and long-term daily oral consumption of SPP was found to be safe in albino Wistar rats for up to 3 months. Thus, SPP may be safe for clinical use as an antiurolithiatic formulation.

Matched MeSH terms: Epithelial Cells
Fulltext Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines

Morais C, Rajandram R, Blakeney JS, Iyer A, Suen JY, Johnson DW, et al.

PLoS One, 2021;16(3):e0248983.
PMID: 33765016 DOI: 10.1371/journal.pone.0248983

Expression of the protease sensing receptor, protease activated receptor-2 (PAR2), is elevated in a variety of cancers and has been promoted as a potential therapeutic target. With the development of potent antagonists for this receptor, we hypothesised that they could be used to treat renal cell carcinoma (RCC). The expression of PAR2 was, therefore, examined in human RCC tissues and selected RCC cell lines. Histologically confirmed cases of RCC, together with paired non-involved kidney tissue, were used to produce a tissue microarray (TMA) and to extract total tissue RNA. Immunohistochemistry and qPCR were then used to assess PAR2 expression. In culture, RCC cell lines versus primary human kidney tubular epithelial cells (HTEC) were used to assess PAR2 expression by qPCR, immunocytochemistry and an intracellular calcium mobilization assay. The TMA revealed an 85% decrease in PAR2 expression in tumour tissue compared with normal kidney tissue. Likewise, qPCR showed a striking reduction in PAR2 mRNA in RCC compared with normal kidney. All RCC cell lines showed lower levels of PAR2 expression than HTEC. In conclusion, we found that PAR2 was reduced in RCC compared with normal kidney and is unlikely to be a target of interest in the treatment of this type of cancer.

Matched MeSH terms: Epithelial Cells/metabolism
[Exploring molecular mechanisms of fucoidan in improving human proximal renal tubular epithelial cells aging by targeting autophagy signaling pathways]

Fang QJ, Liu JJ, Wan YG, Liu BH, Tu Y, Wu W, et al.

Zhongguo Zhong Yao Za Zhi, 2020 Dec;45(24):6003-6011.
PMID: 33496141 DOI: 10.19540/j.cnki.cjcmm.20200709.401

Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 μg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated β-galactosidase(SA-β-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.

Matched MeSH terms: Epithelial Cells
Relative quantification of human β‑defensins gene expression in pterygium and normal conjunctiva samples

Abubakar SA, Isa MM, Omar N, Tan SW

Mol Med Rep, 2020 Dec;22(6):4931-4937.
PMID: 33174018 DOI: 10.3892/mmr.2020.11560

The human ocular surface produces highly conserved cationic peptides. Human β‑defensins (HBDs) serve an important role in innate and adaptive immunity. They are primarily expressed in epithelial cells in response to infection and provide the first line of defence against invading microbes. Defensin β1 (DEFB1) is constitutively expressed and regulated by inflammatory mediators including interferon‑γ, lipopolysaccharide and peptidoglycans. DEFB4A is locally induced in response to microbial infection while DEFB109 is induced via Toll‑like receptor 2. The present study examined the expression of the HBD DEFB1, DEFB4A and DEFB109 genes in pterygium. The pterygium tissues and normal conjunctiva samples were obtained from 18 patients undergoing pterygium surgery. The reverse transcription‑quantitative polymerase chain reaction method was employed to determine the expression of DEFB1, DEFB4A and DEFB109 genes. The results revealed that the expression of DEFB1 and DEFB4A was significantly higher and upregulated in pterygium samples when compared with normal conjunctiva samples from each patient (P<0.05), while the expression of DEFB109 was observed to be lower in pterygium samples when compared with normal samples from the same patient. Previous studies have revealed that DEFB1 and DEFB4A genes are present in low concentrations inside the human eye, and they are upregulated during the maturation of keratinocytes, suggesting a possible role in cell differentiation. The DEFB109 gene is present in higher concentrations inside the human eye, though it is newly discovered. It has also been reported that DEFB1 may be involved in carcinogenesis epithelial tumours. Collectively, the current data suggests that HBDs may serve a crucial role in the pathogenesis and development of pterygia, and thus may be considered as novel molecular targets in understanding pterygia development.

Matched MeSH terms: Epithelial Cells/metabolism
In Vitro Analyses of Interactions Between Colonic Myofibroblasts and Colorectal Cancer Cells for Anticancer Study

Musa M, Ouaret D, Bodmer WF

Anticancer Res, 2020 Nov;40(11):6063-6073.
PMID: 33109544 DOI: 10.21873/anticanres.14627

BACKGROUND/AIM: Interactions between colorectal cancer (CRC) cells and myofibroblasts govern many processes such as cell growth, migration, invasion and differentiation, and contribute to CRC progression. Robust experimental tests are needed to investigate the nature of these interactions for future anticancer studies. The purpose of the study was to design and validate in vitro assays for studying the communication between myofibroblasts and CRC epithelial cell lines.
MATERIALS AND METHODS: The influence of co-culture of myofibroblasts and CRC cell lines is discussed using various in vitro assays including direct co-culture, transwell assays, Matrigel-based differentiation and cell invasion experiments.
RESULTS: The results from these in vitro assays clearly demonstrated various aspects of the crosstalk between myofibroblasts and CRC cell lines, which include cell growth, differentiation, migration and invasion.
CONCLUSION: The reported in vitro assays provide a basis for investigating the factors that control the myofibroblast-epithelial cell interactions in CRC in vivo.

Matched MeSH terms: Epithelial Cells/drug effects
Fulltext Preparation, characterization and therapeutic properties of gum arabic-stabilized gallic acid nanoparticles

Hassani A, Azarian MMS, Ibrahim WN, Hussain SA

Sci Rep, 2020 10 20;10(1):17808.
PMID: 33082415 DOI: 10.1038/s41598-020-71175-8

Gallic acid (GA) is a natural phenolic compound with therapeutic effects that are often challenged by its rapid metabolism and clearance. Therefore, GA was encapsulated using gum arabic into nanoparticles to increase its bioavailability. The formulated nanoparticles (GANPs) were characterized for physicochemical properties and size and were then evaluated for antioxidant and antihypertensive effects using various established in vitro assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging (NO), β-carotene bleaching and angiotensin-converting enzyme (ACE) inhibitory assays. The GANPs were further evaluated for the in vitro cytotoxicity, cell uptake and cell migration in four types of human cancer cell lines including (MCF-7, MDA-MB231) breast adenocarcinoma, HepG2 hepatocellular cancer, HT-29 colorectal adenocarcinoma, and MCF-10A breast epithelial cell lines. The GANPs demonstrated potent antioxidant effects and have shown promising anti-cancer properties in a dose-dependent manner with a predilection toward HepG2 and MCF7 cancer cells. The uptake of GANPs was successful in the majority of cancer cells with a propensity to accumulate in the nuclear region of the cells. The HepG2 and MCF7 cancer cells also had a significantly higher percentage of apoptosis and were more sensitive to gallic acid nanoparticle treatment in the cell migration assay. This study is the first to confirm the synergistic effects of gum arabic in the encapsulation of gallic acid by increasing the selectivity towards cancer cells and enhancing the antioxidant properties. The formulated nanoparticles also had remarkably low toxicity in normal cells. Based on these findings, GANPs may have promising therapeutic applications towards the development of more effective treatments with a probable targeting precision in cancer cells.

Matched MeSH terms: Epithelial Cells/drug effects; Epithelial Cells/physiology*
Rutin loaded liquid crystalline nanoparticles inhibit lipopolysaccharide induced oxidative stress and apoptosis in bronchial epithelial cells in vitro

Paudel KR, Wadhwa R, Mehta M, Chellappan DK, Hansbro PM, Dua K

Toxicol In Vitro, 2020 Oct;68:104961.
PMID: 32771431 DOI: 10.1016/j.tiv.2020.104961

Airway inflammation and infections are the primary causes of damage in the airway epithelium, that lead to hypersecretion of mucus and airway hyper-responsiveness. The role of reactive oxygen species (ROS) and their components in the pathophysiological mechanisms of airway inflammation have been well-studied and emphasized for the past several decades. Rutin, a potent bioflavonoid, is well-known for its antioxidant, anti-inflammatory, especially in bronchial inflammation. However, poor solubility and rapid metabolism have led to its low bioavailability in biological systems, and hence limit its application. The present study aims to investigate the beneficial effects of rutin-loaded liquid crystalline nanoparticles (LCNs) against lipopolysaccharide (LPS) induced oxidative damage in human bronchial epithelial cell line (BEAS-2-B) cells in vitro. LPS was used to stimulate BEAS-2-B cells, causing the generation of nitric oxide (NO) and other reactive oxygen species (ROS) that had led to cellular apoptosis. The levels of NO and ROS were detected by, Griess reagent kit and dichlorodihydrofluorescein diacetate (DCFH-DA) respectively, whereas, cell apoptosis was studied by Annexin V-FITC and PI staining. The findings revealed that rutin-loaded LCNs significantly reduced NO, ROS levels and prevented apoptosis in BEAS-2B cells. The observations and findings provide a mechanistic understanding of the effectiveness of rutin-loaded LCNs in protecting the bronchial cells against airway inflammation, thus possessing a promising therapeutic option for the management of airway diseases.

Matched MeSH terms: Epithelial Cells/drug effects*
Cytokine Induction in Nipah Virus-Infected Primary Human and Porcine Bronchial Epithelial Cells

Elvert M, Sauerhering L, Maisner A

J Infect Dis, 2020 05 11;221(Suppl 4):S395-S400.
PMID: 31665348 DOI: 10.1093/infdis/jiz455

During the Nipah virus (NiV) outbreak in Malaysia, pigs and humans were infected. While pigs generally developed severe respiratory disease due to effective virus replication and associated inflammation processes in porcine airways, respiratory symptoms in humans were rare and less severe. To elucidate the reasons for the species-specific differences in NiV airway infections, we compared the cytokine responses as a first reaction to NiV in primary porcine and human bronchial epithelial cells (PBEpC and HBEpC, respectively). In both cell types, NiV infection resulted in the expression of type III interferons (IFN-λ). Upon infection with similar virus doses, viral RNA load and IFN expression were substantially higher in HBEpC. Even if PBEpC expressed the same viral RNA amounts as NiV-infected HBEpC, the porcine cells showed reduced IFN- and IFN-dependent antiviral gene expression. Despite this inherently limited IFN response, the expression of proinflammatory cytokines (IL-6, IL-8) in NiV-infected PBEpC was not decreased. The downregulation of antiviral activity in the presence of a functional proinflammatory cytokine response might be one of the species-specific factors contributing to efficient virus replication and acute inflammation in the lungs of pigs infected with the Malaysian NiV strain.

Matched MeSH terms: Epithelial Cells/virology*
The differential effects of commercial specialized media on cell growth and transforming growth factor beta 1-induced epithelial-mesenchymal transition in bronchial epithelial cells

Hasan NAHM, Harith HH, Israf DA, Tham CL

Mol Biol Rep, 2020 May;47(5):3511-3519.
PMID: 32279207 DOI: 10.1007/s11033-020-05439-x

Epithelial-mesenchymal transition (EMT) is one of the mechanisms that contribute to bronchial remodelling which underlie chronic inflammatory airway diseases such as chronic obstructive pulmonary disorder (COPD) and asthma. Bronchial EMT can be triggered by many factors including transforming growth factor β1 (TGFβ1). The majority of studies on TGFβ1-mediated bronchial EMT used BEGM as the culture medium. LHC-9 medium is another alternative available which is more economical but a less common option. Using normal human bronchial epithelial cells (BEAS-2B) cultured in BEGM as a reference, this study aims to validate the induction of EMT by TGFβ1 in cells cultured in LHC-9. Briefly, the cells were maintained in either LHC-9 or BEGM, and induced with TGFβ1 (5, 10 and 20 ng/ml) for 48 h. EMT induction was confirmed by morphological analysis and EMT markers expression by immunoblotting. In both media, cells induced with TGFβ1 displayed spindle-like morphology with a significantly higher radius ratio compared to non-induced cells which displayed a cobblestone morphology. Correspondingly, the expression of the epithelial marker E-cadherin was significantly lower, whereas the mesenchymal marker vimentin expression was significantly higher in induced cells, compared to non-induced cells. By contrast, a slower cell growth rate was observed in LHC-9 compared to that of BEGM. This study demonstrates that neither LHC-9 nor BEGM significantly influence TGFβ1-induced bronchial EMT. However, LHC-9 is less optimal for bronchial epithelial cell growth compared to BEGM. Thus, LHC-9 may be a more cost-effective substitute for BEGM, provided that time is not a factor.

Matched MeSH terms: Epithelial Cells/cytology; Epithelial Cells/drug effects; Epithelial Cells/metabolism
Fulltext Good Visual Outcome Following Corticosteroid Treatment for Compressive Optic Neuropathy Secondary to Sinonasal Carcinoma

Mohammad Razali A, Mohd Zain A, Bt Wan Abdul Halim WH, Md Din N

Cureus, 2020 Apr 18;12(4):e7732.
PMID: 32440379 DOI: 10.7759/cureus.7732

Most patients with sinonasal carcinoma present to the otorhinolaryngologist with nasal symptoms. It is however uncommon for them to present with acute visual loss at first presentation. We report a case of compressive optic neuropathy secondary to sinonasal carcinoma, which presented acutely with right eye blurring of vision upon waking up. Computed tomography (CT) of the brain and orbit with contrast showed a locally invasive nasopharyngeal mass extending into the right orbit and cranial fossa. Histopathological examination revealed squamous cell sinonasal carcinoma. Her visual acuity improved with a three-day course of pulsed intravenous methylprednisolone 1 g per day, followed by a gradual tapering dose of oral prednisolone (1 mg/kg/day).

Matched MeSH terms: Epithelial Cells
Fulltext Monoamine oxidase A is down-regulated in EBV-associated nasopharyngeal carcinoma

Lee HM, Sia APE, Li L, Sathasivam HP, Chan MSA, Rajadurai P, et al.

Sci Rep, 2020 04 09;10(1):6115.
PMID: 32273550 DOI: 10.1038/s41598-020-63150-0

Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we identify for the first time a role for monoamine oxidase A (MAOA) in NPC. MAOA is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines. Depending on the cancer type, MAOA can either have a tumour-promoting or tumour-suppressive role. We show that MAOA is down-regulated in primary NPC tissues and its down-regulation enhances the migration of NPC cells. In addition, we found that EBV infection can down-regulate MAOA expression in both pre-malignant and malignant nasopharyngeal epithelial (NPE) cells. We further demonstrate that MAOA is down-regulated as a result of IL-6/IL-6R/STAT3 signalling and epigenetic mechanisms, effects that might be attributed to EBV infection in NPE cells. Taken together, our data point to a central role for EBV in mediating the tumour suppressive effects of MAOA and that loss of MAOA could be an important step in the pathogenesis of NPC.

Matched MeSH terms: Epithelial Cells/metabolism
Gene expression changes in human bronchial epithelial cells (BEAS-2B) and human pulmonary alveolar epithelial cells (HPAEpiC) after interaction with Cladosporium sphaerospermum

Lo SG, Wong SF, Mak JW, Choo KK, Ng KP

Med Mycol, 2020 Apr 01;58(3):333-340.
PMID: 31309220 DOI: 10.1093/mmy/myz061

Cladosporium is one of the most abundant spore. Fungi of this genus can cause respiratory allergy and intrabronchial lesion. We studied the differential expression of host genes after the interaction of Cladosporium sphaerospermum conidia with Human Bronchial Epithelial Cells (BEAS-2B) and Human Pulmonary Alveolar Epithelial Cells (HPAEpiC). C. sphaerospermum conidia were harvested and co-cultured with BEAS-2B cells or HPAEpiC cells for 48 hours respectively. This culture duration was chosen as it was associated with high germination rate. RNA was extracted from two biological replicates per treatment. RNA of BEAS-2B cells was used to assess changes in gene expression using AffymetrixGeneChip® Human Transcriptome Array 2.0. After co-culture with Cladosporium spores, 68 individual genes were found differentially expressed (P ≤ 0.05) and up-regulated ≥ 1.5 folds while 75 genes were found differentially expressed at ≤ -1.5 folds compared with controls. Reverse transcription and qPCR were performed on the RNA collected from both BEAS-2B cells and HPAEpiC cells to validate the microarray results with 7 genes. Based on the findings, infected pulmonary epithelial cells exhibited an increase in cell death-related genes and genes associated with innate immunity.

Matched MeSH terms: Epithelial Cells
Fulltext Zonula occludens and nasal epithelial barrier integrity in allergic rhinitis

Siti Sarah CO, Md Shukri N, Mohd Ashari NS, Wong KK

PeerJ, 2020;8:e9834.
PMID: 32953271 DOI: 10.7717/peerj.9834

Allergic rhinitis (AR) is a common disease affecting 400 million of the population worldwide. Nasal epithelial cells form a barrier against the invasion of environmental pathogens. These nasal epithelial cells are connected together by tight junction (TJ) proteins including zonula occludens-1 (ZO-1), ZO-2 and ZO-3. Impairment of ZO proteins are observed in AR patients whereby dysfunction of ZOs allows allergens to pass the nasal passage into the subepithelium causing AR development. In this review, we discuss ZO proteins and their impairment leading to AR, regulation of their expression by Th1 cytokines (i.e., IL-2, TNF-α and IFN-γ), Th2 cytokines (i.e., IL-4 and IL-13) and histone deacetylases (i.e., HDAC1 and HDAC2). These findings are pivotal for future development of targeted therapies by restoring ZO protein expression and improving nasal epithelial barrier integrity in AR patients.

Matched MeSH terms: Epithelial Cells
Fulltext Differential Response of Gestational Tissues to TLR3 Viral Priming Prior to Exposure to Bacterial TLR2 and TLR2/6 Agonists

Rasheed ZBM, Lee YS, Kim SH, Rai RK, Ruano CSM, Anucha E, et al.

Front Immunol, 2020;11:1899.
PMID: 32983111 DOI: 10.3389/fimmu.2020.01899

Background: Infection/inflammation is an important causal factor in spontaneous preterm birth (sPTB). Most mechanistic studies have concentrated on the role of bacteria, with limited focus on the role of viruses in sPTB. Murine studies support a potential multi-pathogen aetiology in which a double or sequential hit of both viral and bacterial pathogens leads to a higher risk preterm labour. This study aimed to determine the effect of viral priming on bacterial induced inflammation in human in vitro models of ascending and haematogenous infection. Methods: Vaginal epithelial cells, and primary amnion epithelial cells and myocytes were used to represent cell targets of ascending infection while interactions between peripheral blood mononuclear cells (PBMCs) and placental explants were used to model systemic infection. To model the effect of viral priming upon the subsequent response to bacterial stimuli, each cell type was stimulated first with a TLR3 viral agonist, and then with either a TLR2 or TLR2/6 agonist, and responses compared to those of each agonist alone. Immunoblotting was used to detect cellular NF-κB, AP-1, and IRF-3 activation. Cellular TLR3, TLR2, and TLR6 mRNA was quantified by RT-qPCR. Immunoassays were used to measure supernatant cytokine, chemokine and PGE2 concentrations. Results: TLR3 ("viral") priming prior to TLR2/6 agonist ("bacterial") exposure augmented the pro-inflammatory, pro-labour response in VECs, AECs, myocytes and PBMCs when compared to the effects of agonists alone. In contrast, enhanced anti-inflammatory cytokine production (IL-10) was observed in placental explants. Culturing placental explants in conditioned media derived from PBMCs primed with a TLR3 agonist enhanced TLR2/6 agonist stimulated production of IL-6 and IL-8, suggesting a differential response by the placenta to systemic inflammation compared to direct infection as a result of haematogenous spread. TLR3 agonism generally caused increased mRNA expression of TLR3 and TLR2 but not TLR6. Conclusion: This study provides human in vitro evidence that viral infection may increase the susceptibility of women to bacterial-induced sPTB. Improved understanding of interactions between viral and bacterial components of the maternal microbiome and host immune response may offer new therapeutic options, such as antivirals for the prevention of PTB.

Matched MeSH terms: Epithelial Cells/drug effects; Epithelial Cells/immunology; Epithelial Cells/metabolism
Fulltext Correlation between salivary estrogen levels and oral epithelial cytokeratin 5 expression

Handajani J, Effendi N, Sosroseno W

F1000Res, 2020;9:186.
PMID: 32399205 DOI: 10.12688/f1000research.22536.2

Background: Estrogen expression levels may be associated with age and may affect keratinization of the hard palate. Keratinized epithelium expresses cytokeratin 5 and 14 in the basal layer. The aim of this study was to determine the correlation between the levels of salivary estrogen and number of cytokeratin 5-positive oral epithelial cells. Methods: A total of 30 female subjects were recruited and divided into children, adults and elderly (N=10 per group). Salivary estrogen levels and cytokeratin 5-expressing oral epithelial cells were assessed using ELISA and immunohistological methods, respectively. Data were analyzed using ANOVA with post hoc LSD test and Pearson's correlation coefficient. Results: The results showed that both the number of cytokeratin 5-positive cells and the level of salivary estrogen were significantly higher in adults but decreased in the elderly, as compared with those in children (p<0.05). Furthermore, the levels of salivary estrogen were significantly correlated with the number of cytokeratin 5-positive cells (r=0.815). The ANOVA result showed significance difference cytokeratin 5 expression and estrogen level (p<0.05). The post hoc LSD test revealed cytokeratin 5 expression and estrogen level to be significantly different in children, adults, and elderly participants (p<0.05). Conclusions: These results suggest that the profile of salivary estrogen and oral epithelial cell-expressed cytokeratin 5 may be positively correlated with age and depend on age.

Matched MeSH terms: Epithelial Cells/metabolism*
Fulltext Detrimental Effects of UVB on Retinal Pigment Epithelial Cells and Its Role in Age-Related Macular Degeneration

Mahendra CK, Tan LTH, Pusparajah P, Htar TT, Chuah LH, Lee VS, et al.

Oxid Med Cell Longev, 2020;2020:1904178.
PMID: 32855763 DOI: 10.1155/2020/1904178

Retinal pigment epithelial (RPE) cells are an essential part of the human eye because they not only mediate and control the transfer of fluids and solutes but also protect the retina against photooxidative damage and renew photoreceptor cells through phagocytosis. However, their function necessitates cumulative exposure to the sun resulting in UV damage, which may lead to the development of age-related macular degeneration (AMD). Several studies have shown that UVB induces direct DNA damage and oxidative stress in RPE cells by increasing ROS and dysregulating endogenous antioxidants. Activation of different signaling pathways connected to inflammation, cell cycle arrest, and intrinsic apoptosis was reported as well. Besides that, essential functions like phagocytosis, osmoregulation, and water permeability of RPE cells were also affected. Although the melanin within RPE cells can act as a photoprotectant, this photoprotection decreases with age. Nevertheless, the changes in lens epithelium-derived growth factor (LEDGF) and autophagic activity or application of bioactive compounds from natural products can reverse the detrimental effect of UVB. Additionally, in vivo studies on the whole retina demonstrated that UVB irradiation induces gene and protein level dysregulation, indicating cellular stress and aberrations in the chromosome level. Morphological changes like retinal depigmentation and drusen formation were noted as well which is similar to the etiology of AMD, suggesting the connection of UVB damage with AMD. Therefore, future studies, which include mechanism studies via in vitro or in vivo and other potential bioactive compounds, should be pursued for a better understanding of the involvement of UVB in AMD.

Matched MeSH terms: Epithelial Cells/pathology; Epithelial Cells/radiation effects*

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links