2020

Permanent URI for this collectionhttps://hdl.handle.net/1807/98905

Browse

Now showing 1 - 20 of 46

The mechanism of BAF60c in myocardial metabolism through the PGC1α/PPARα/mTOR signaling pathway in rats with heart failure
(Canadian Science Publishing, 2020-09-30) Chen, Qiang; Chen, Lizhu; Jian, Jianguo; Li, Junping; Zhang, Xiaomiao
BRM-associated factor (BAF) 60c promotes muscle glycolysis and improves glucose homeostasis. This study explored the mechanism of BAF60c in heart failure (HF). Fetal/adult rat models of HF were established, and the levels of cardiac contractile proteins and energy metabolism-, oxidative metabolism- and glycolysis-related factors were detected. Overexpression/siRNA BAF60c plasmids were injected into adult HF rats to estimate myocardial glucose uptake, high-energy phosphate contents, mitochondrial function, and cell proliferation and apoptosis. The overexpression/siRNA BAF60c plasmids were transfected into cardiac hypertrophic H9C2 cells to explore the in vitro effects. The interaction of BAF60c and PGC1α was detected. The results suggested that adult HF rats presented increased levels of fetal proteins (ssTnI and fTnT), BAF60c and glycolysis-related factors, and reduced levels of cardiac contractile proteins, PGC1α, PPARα, and oxidative metabolism-related factors. BAF60c knockdown improved glucose uptake, maintained the oxidative metabolism/glycolysis balance, promoted H9C2 cell proliferation, and inhibited apoptosis. PGC1α interacted with BAF60c. Knocking down BAF60c also activated the PGC1α/PPARα/mTOR pathway. Overexpression of PGC1α decreased the damage to H9C2 cells caused by BAF60c. Altogether, BAF60c downregulation activated the PGC1α/PPARα/mTOR pathway, maintained the oxidative metabolism/glycolysis balance and improved mitochondrial function in rat models of HF. This study may offer novel insights into HF treatment.
EGFR activity upregulates lactate dehydrogenase A (LDHA) expression, LDH activity and lactate secretion in cultured IB3-1 cystic fibrosis lung epithelial cells
(Canadian Science Publishing, 2020-12-29) Massip-Copiz, Mara Macarena; Valdivieso, ngel Gabriel; Clauzure, Maringeles; Mori, Consuelo; Asensio, Cristian J. A.; Aguilar, Mara ngeles; Santa-Coloma, Toms
Cystic fibrosis (CF) is caused by mutations in the CFTR gene. It has been postulated that a reduced HCO3
EDTA as a chelating agent in quantitative 1H-NMR of biologically important ions
(Canadian Science Publishing, 2020-12-17) Mathuthu, Emmanuel; Janse van Rensburg, Angelique; Du Plessis, Dean; Mason, Shayne
Biologically important ions (Ca, K, Mg, Fe, and Zn) play major roles in numerous biological processes, with their homeostatic balance being necessary for the maintenance of cellular mechanisms. Sudden and severe loss in homeostasis of just one biologically important ion can cause cascading negative effects. Being able to quickly, accurately and reliably quantify biologically important ions in human bio-fluid samples is something that has been sorely lacking within the field of metabolomics. 1H-NMR is a well-known analytical platform in metabolomics but ions are invisible on 1H-NMR spectra. The foundation of our investigation was based upon a priori knowledge that free EDTA produce two clear single peaks on 1H-NMR spectra, and that EDTA chelated to different ions produce unique 1H-NMR spectral patterns due to 3D conformational changes in the chemical structure of chelated-EDTA and varying degrees of electronegativity. The aim of this study was to develop and test a 1H-NMR-based method, with application specifically to the field of metabolomics, to quantify biologically important ions within the physiological pH range of 6.50-7.50 using EDTA as a chelating agent. Our method produced linear, accurate, precise and repeatable results for Ca, Mg and Zn; however, K and Fe did not chelate with EDTA
Metastatic TNBC is highly associated with a fused mitochondrial morphology and a glycolytic and lipogenic metabolism programmation
(Canadian Science Publishing, 2020-11-21) Prez-Trevio, Perla; Aguayo-Milln, Claudia D.; Santuario-Facio, Sandra Karina; Vela-Guajardo, Jorge E.; Salazar, Esteban; Camacho-Morales, Alberto; Ortiz, Roco; Garca, Noem
Mitochondria modify their function and morphology to satisfice the bioenergetic demand of the cells. Cancer cells take advantage of these features to sustain their metabolic, proliferative, metastatic, and survival necessities. Therefore, the understanding of mitochondrial morphologic changes of the different grades of Triple-Negative Breast Cancer (TNBC) could be relevant for the design of novel treatments. Consequently, this research aimed to explore the mitochondria morphology and gene expression of some proteins related to mitochondrial dynamics as well as proteins related to oxidative and non-oxidative metabolism of metastatic and non-metastatic TNBC. We found that mitochondrial-morphology and metabolism are different between metastatic and non-metastatic TNBC. Metastatic TNBC showed overexpression of genes related to mitochondrial dynamics, fatty acids, and glycolytic metabolism. These features were accompanied by a fused mitochondrial morphology. In contrast, the non-metastatic TNBC presented a stress-associated mitochondrial morphology, hyperfragmented mitochondria accompanied by upregulated expression of mitochondrial biogenesis-related genes, both characteristics related to the higher ROS production observed in this cell line. These differences found between metastatic and non-metastatic TNBC will allow a better understanding of the metastasis process and the improvement of the development of a specific and personalized TNBC therapy.
Thidiazuron suppresses breast cancer progression via targeting miR-132 and miR-202-5p/PTEN axis mediated dysregulation of PI3K/AKT signaling pathway
(Canadian Science Publishing, 2020-10-02) Ibrahim, Hairul-Islam; Ismail, Mohammad Bani; Ammar, Rebai Ben; Ahmed, Emad
Chemo-resistance and metastatic disease development are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator, its biological role on human and animals has not been yet clarified. In the present study, we investigated the anticancer activity of this plant phytohormone on the drug resistant-triple negative breast cancer MDA-MB-231 cell line. Treatment of the breast cancer cells with TDZ (1-50 μM) caused more stressful environment and induced a significant increase in percentages of active caspases positive cells. In addition, TDZ treatment (5 and 10 μM) significantly attenuated the migration and the invasion activities of these highly metastatic cancer cells. Mechanistically, TDZ reducesd cancer progression and invasive activity through targeting miR-202-5p, which stimulatesd the expression of the phosphatase and tensin homolog (PTEN), the tumor suppressor that downregulates PI3K/AKT signaling pathway. In the meantime, TDZ treatment statistically upregulatesd the suppressor of breast cancer proliferation, miRNA-132 that is also implicated in dysregulating the TEN-AKT/the nuclear factor NFκB signaling pathway. Interestingly, our molecular docking analysis revealed potential non-covalent interaction between TDZ with AKT, PTEN and PI3K. These findings suggest that TDZ may suppresses breast cancer metastasis through targeting miRNA-132, miR-202-5p/PTEN and PI3K/AKT downstream molecules.
TFAP2A inhibits microRNA-126 expression at a transcriptional level to aggravate ischemic neuronal injury
(Canadian Science Publishing, 2020-11-21) Gao, Zhiqiang; Zhang, Jiang; Wu, Yunxia
Neuronal injury induced by cerebral ischemia poses a serious risk to health worldwide, which lacks effective clinical therapies currently. This study was performed to investigate the effect of transcription factor AP-2 alpha (TFAP2A) and the underlying mechanism in oxygen-glucose deprivation (OGD) cell model and transient global cerebral ischemia (tGCI) rat model. Based on CCK-8 and Hoechst staining results, silencing of TFAP2A could enhance the viability of OGD-treated PC12 cells and decrease the apoptotic rate of cells. ChIP assay was performed to detect the binding of TFAP2A to the promoter region of microRNA (miR)-126, and we found that TFAP2A could inhibit miR-126 expression. Further mechanistic investigation showed that miR-126 targeted polo like kinase 2 (PLK2), while overexpression of PLK2 activated the IκBα/NF-κB pathway and further suppressed the growth of OGD-treated PC12 cells. As for in vivo assay, proportion of infarction area in brain tissues of rats was analyzed by TTC staining, whereas Nissl staining was applied to evaluate the number of surviving brain neurons. The pathological condition of neuronal injury in rat brain tissues was monitored using HE staining. Results suggested that TFAP2A downregulated miR-126 to upregulate PLK2 and activate IκBα/NF-κB pathway, which deteriorated neuronal injury following ischemia in vivo.
Dystonin loss-of-function leads to impaired autophagy-endolysosomal pathway dynamics
(Canadian Science Publishing, 2020-12-11) Lynch-Godrei, Anisha; De Repentigny, Yves; Ferrier, Andrew; Gagnon, Sabrina; Kothary, Rashmi
The neuronal dystonin protein (DST-a) is a large cytoskeletal linker important for integrating the various components of the cytoskeleton. Recessive Dst mutations lead to a sensory neuropathy in mice known as dystonia musculorum (Dst
Upregulation of Bromodomain PHD‑finger transcription factor in ovarian cancer and its critical role for cancer cell proliferation and survival
(Canadian Science Publishing, 2020-08-28) Miao, Juan; Zhang, Min; Huang, Xiaohao; Xu, Lei; Tang, Ranran; Wang, Huan; Han, Suping
Abstract: Bromodomain PHD finger transcription factor (BPTF) is a core subunit of nucleosome-remodeling factor (NURF) complex, which plays an important role in the development of several cancers. However, it is unknown whether BPTF regulates ovarian cancer (OC) progression. Relative expression of BPTF in cell lines and tissues of OC were measured by Western blot and immunohistochemistry respectively. Clinical significance of BPTF in OC was analyzed by Chisquare test. BPTF knockdown effects on the proliferation, migration, invasion and apoptosis of OC cells were examined. Mechanism studies revealed that these effects were achieved through simultaneous modulation of multiple signaling pathways. We found that BPTF was highly expressed in OC cell lines and tissues compared with normal human ovarian epithelial cell and non-cancerous tissues (p
MiR-494-3p alleviates acute lung injury through regulating NLRP3 activation by targeting CMPK2
(Canadian Science Publishing, 2020-08-17) Wang, Hong; Wang, Shuqin; Huang, Shanshan
Acute lung injury (ALI) is a severe respiratory disorder with high mortality, and is characterized by excessive cell apoptosis and inflammation. MicroRNAs (miRNAs) play pivotal roles in ALI. The present study aimed to probe into the biological function of miR-494-3p in cell apoptosis and inﬂammatory response in ALI. Mice were injected with lipopolysaccharide (LPS) to mimic the in vivo ALI model. WI-38 cells were stimulated with LPS to mimic the in vitro ALI model. MiR-494-3p was significantly downregulated in ALI mice and in LPS induced WI-38 cells. Overexpression of miR-494-3p inhibited inflammation and cell apoptosis in LPS-induced WI-38 cells, as well as improved lung injury of ALI mice. Then, cytidine/uridine monophosphate kinase 2 (CMPK2) was identified as a novel target of miR-494-3p in WI-38 cells. Furthermore, miR-494-3p suppressed cell apoptosis and inflammatory response in LPS-treated WI-38 cells through targeting CMPK2. NLRP3 inflammasome has been reported to be responsible for the activation of inflammatory processes. In our study, CMPK2 was confirmed to activate NLRP3 inflammasome in LPS-treated WI-38 cells. In conclusion, miR-494-3p attenuates ALI through inhibiting cell apoptosis and inflammatory response by targeting CMPK2, which may shed light on the improvement of the treatment for ALI.
Silencing linc00662 inhibits cell proliferation and colony formation of lung cancer cells via regulating miR-145-5p/PAFAH1B2 axis
(Canadian Science Publishing, 2020-03-24) Xu, Zhe-yuan; Peng, Jun; Shi, Zhi-zhou; Chen, Xin-long; Cheng, Hong-zhong; Wang, Han; Wang, Yang; Wang, Guo-ping; Jiang, Wen; Peng, Hao
Lung cancer is the most common cause of cancer-related death in the world. Long non-coding RNAs (lncRNAs) are longer than 200 nucleotides transcripts which are not translated into protein. Linc00662 is overexpressed in lung cancer. However, the roles of linc00662 involved in lung cancer progression are still unknown. In our study, we found that linc00662 was overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) by analyzing the TCGA data. We knockdown the linc00662 expression using siRNAs and found that silencing linc00662 significantly inhibited the proliferation and colony formation of A549 and H460 cells. We further found that knockdown of linc00662 increased the miR-145-5p expression and decreased PAFAH1B2 expression. We further showed that linc00662 could bind with miR-145-5p, and miR-145-5p could bind to the 3’UTR of PAFAH1B2. miR-145-5p could negatively regulate PAFAH1B2 both in the mRNA and protein levels. Loss of miR-145-5p could abolish the inhibitory effects of silencing linc00662 on the proliferation and colony formation of A549 and H460 cells. All these findings revealed that linc00662 functioned as an oncogene by acting as competing endogenous RNA (ceRNA) to sponge and regulate miR-145-5p in lung cancer and may provide a potential target of lung cancer treatment.
Circ_0000043 promotes breast cancer cell proliferation, migration, invasion and epithelial-mesenchymal transition via the miR-136/ Smad3 axis
(Canadian Science Publishing, 2020-09-08) Leng, Xiaoling; Huang, Guofu; Ding, Jianbing; Ma, Fucheng
Circular RNAs (circRNAs) are a type of tissue-specific RNA with more stable structure than linear RNAs, and its association with breast cancer (BC) is poorly understood. This study aimed at probing the biological effect of circ_0000043 in the progression of BC. In this study, expression of circ_0000043 in BC tissue samples was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) and Western blot were used to detect the expression of Smad family member 3 (Smad3). CCK-8, wound healing and Transwell assays were used to assess the effect of circ_0000043 in regulating BC cell proliferation, migration and invasion. Moreover, the binding relationships between circ_0000043 and miR-136, and miR-136 and Smad3 were detected by dual-luciferase reporter assay. Additionally, Western blot was used to detect the expressions of markers related to epithelial-mesenchymal transition (EMT), including E-cadherin, N-cadherin and vimentin. Our results showed that circ_0000043 expression was up-regulated in BC tissues and cell lines. Proliferation, migration, invasion and EMT of BC cells were significantly inhibited by circ_0000043 knockdown, and overexpression of circ_0000043 had the opposite effects. Additionally, circ_0000043 could up-regulate Smad3 expression by sponging miR-136. In conclusion, our study demonstrates that circ_0000043 can promote BC progression via regulating the miR-136/Smad3 axis.
Automated classification of mitotic catastrophe by use of the centromere fragmentation morphology.
(Canadian Science Publishing, 2020-08-28) Roy, Kaushiki; Lewis, Cody W; Chan, Gordon; Bhattacharjee, Debotosh
Mitotic catastrophe is a common mode of tumor cell death. Cancer cells with defective cell-cycle checkpoint often enter mitosis with damaged or under replicated chromosomes following genotoxic treatment. Premature condensation of the under-replicated (or damaged) chromosomes results in double-stranded DNA breaks at the centromere (centromere fragmentation). Centromere fragmentation is a morphological marker of mitotic catastrophe and is distinguished by the clustering of centromeres away from the chromosomes. We present an automated 2-step system for segmentation of cells exhibiting centromere fragmentation. The first step segments individual cells from clumps. We added two new terms, Weighted Local Repelling term (WLRt) and Weighted Gradient term (WGt), in the energy functional of the traditional Chan Vese based level set method. WLRt was used to generate a repelling force when contours of adjacent cells merged and then penalized the overlap. WGt enhances gradients between overlapping cells. The second step consists of a new algorithm, SBaN (Shape-Based analysis of each nuclei), which extracts features like circularity, major-axis length, minor-axis length, area, and eccentricity from each chromosome to identify cells with centromere fragmentation. The performance of SBaN algorithm for centromere fragmentation detection was statistically evaluated and the results were robust.
The lncRNA TUG1 promotes cell growth and migration via the TUG1/miR-145-5p/TRPC6 pathway in colorectal cancer
(Canadian Science Publishing, 2020-06-05) Wang, Xiaoqiang; Bai, Xiaomin; Yan, Zhonghui; Guo, Xinyu; Zhang, Youcheng
Colorectal cancer (CRC) is the third most prevalent malignant tumor. Taurine upregulated gene 1 (TUG1), a long non-coding RNA (lncRNA), has been shown to be involved in the physiological and pathological processes of CRC. However, the role of TUG1 in the progression of CRC and its underlying mechanism are largely unknown. Here, we measured TUG1 expression in clinical samples from CRC patients and found that TUG1 expression was higher in CRC tissues as compared to that in normal adjacent tissues. We then inhibited TUG1 with siRNAs in two CRC cell lines and found that TUG1 knockdown inhibited the viability, proliferation, and migration of CRC cells and lowered the ability of CRC cells to form subcutaneous tumors. Furthermore, we revealed that TUG1 affected the cellular processes in CRC cells by sponging miR-145-5p. We further found that miR-145-5p inhibited TRPC6 expression, and overexpression of TRPC6 restored the role of miR-145-5p in CRC cells. Collectively, we illustrated that TUG1 manifests its functions by modulating the TUG1/miR-145-5p/TRPC6 regulatory axis. In conclusion, our study revealed a novel molecular mechanism of TUG1 in CRC progression and suggested the potential of the TUG1/miR-145-5p/TRPC6 pathway to serve as a target for the diagnosis and treatment of CRC.
A Canadian perspective on severe acute respiratory syndrome coronavirus 2 infection and treatment: how prevalent underlying inflammatory disease contributes to pathogenesis
(Canadian Science Publishing, 2020-09-16) Willows, Steven Derald; Alam, Syed Benazir; Sandhu, Jagdeep K.; Kulka, Marianna
The coronavirus disease 2019 (COVID-19), a serious respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a global pandemic. Canada reported its first case of COVID-19 on 25th January 2020. By March 2020 the virus had spread within Canadian communities reaching the most frail and vulnerable elderly population in long-term care facilities. The majority of cases were reported in the provinces of Quebec, Ontario, Alberta and British Columbia and the highest mortality was seen among individuals aged 65 years or older. Canada has the highest prevalence and incidence rates of several chronic inflammatory diseases, such as multiple sclerosis, inflammatory bowel disease and Parkinson’s disease. Many elderly Canadians also live with comorbid medical illnesses, such as hypertension, diabetes, cardiovascular disease and chronic lung disease and are more likely to suffer from severe COVID-19 with a poor prognosis. It is becoming increasingly evident that underlying inflammatory disease contributes to SARS-CoV-2 pathogenesis. Here, we review the mechanisms of SARS-CoV-2 infection and the host inflammatory responses that lead to resolution or progression to severe COVID-19 disease. Furthermore, we discuss the landscape of COVID-19 therapeutics that are currently in development in Canada.
hCINAP is a potential direct HIF-1 target gene and is required for hypoxia-induced EMT and apoptosis in cervical cancer cells
(Canadian Science Publishing, 2020-06-08) zhang, yong; jiang, li; qin, nianqun; Cao, Mi; Liang, xiujuan; Wang, Rensheng
The early metastasis of cervical cancer is a multi-step process requiring the cancer cells to adapt to the signal input from different tissue environments, including hypoxia. Hypoxia-induced epithelial-to-mesenchymal transition (EMT) plays a critical role in the acquisition of the ability to invade surrounding tissue. However, the molecular mechanism underlying EMT in cervical cancer remains to be elucidated. Herein, we showed that HIF‑1α and ARNT are recruited to the hCINAP promoter and initiate hCINAP expression in hypoxia. Ablation of hCINAP decreased the migratory capacity and EMT of cervical cancer cells in hypoxia. Furthermore, hCINAP regulates EMT through Akt/mTOR signaling and inhibits hypoxia-induced p53-dependent apoptosis. Our data collectively showed that hCINAP may have essential roles in the metastasis of cervical cancer and could be a potential target for curing cervical cancer.
Transcriptional regulation of human abraxas brother protein 1 expression by yin yang 1
(Canadian Science Publishing, 2020-07-07) Song, Pan; Hong, Jian; Wang, Yuan; Yao, Xuelian; Zhan, Yiqun; Yin, Ronghua; Yu, Miao; Li, Changyan; Yang, Xiaoming; Ge, Changhui
Abraxas brother protein 1 (ABRO1) is a subunit of the deubiquitinating enzyme BRCC36-containing isopeptidase complex and plays important roles in cellular responses to stress by interacting with its binding partners, such as ubiquitin-specific peptidase 7, p53, activating transcription factor 4, THAP-domain containing 5, and serine hydroxymethyltransferase. However, the transcriptional regulation of ABRO1 remains unexplored. In this study, we identified and characterized the core regulatory elements of the human ABRO1 gene and mapped them to the ABRO1 promoter region. Additionally, 5′ rapid amplification of cDNA ends revealed that the transcriptional start site (TSS) was located −13 bp upstream from the start codon. Reporter gene, chromatin immunoprecipitation, and electrophoretic mobility shift assays demonstrated that ABRO1 transcription was regulated through cis-acting elements located in the region −89 to −59 bp upstream of the ABRO1 TSS and that these elements were targeted by yin yang 1 transcription factor (YY1). Moreover, YY1 overexpression increased human ABRO1 mRNA and protein expression, and small-interfering RNA-mediated downregulation of YY1 attenuated ABRO1 expression. These results suggested that YY1 positively regulated human ABRO1 expression by binding to cis-acting elements located in the ABRO1 TSS.
Astragaloside IV enhanced carboplatin sensitivity in prostate cancer by suppressing AKT/NF-κB signaling pathway
(Canadian Science Publishing, 2020-07-03) He, Yi; Zhang, Qimei; Chen, Huan; Guo, Qingxi; Zhang, Liming; Zhang, Zhuo; Li, Yingchuan
In our study, we explored the effect of AgIV on carboplatin chemotherapy in prostate cancer cell lines in vitro and in vivo. Cell viability assay, colony formation assay, flow cytometry, western blot, immunohistochemistry (IHC), immunofluorescence and tumor xenograft growth assay were conducted. We found that AgIV significantly decreased the half maximal inhibitory concentration (IC50) of carboplatin in prostate cancer cell lines LNCap and PC-3. Moreover, AgIV enhanced the effect of carboplatin in suppressing colony formation and inducing cell apoptosis. A low dose carboplatin treatment upregulated N-cadherin and Vimentin expression and downregulated E-cadherin expression, but this effect was abolished by combining with AgIV. Carboplatin treatment increased the levels of p-AKT and p-p65 and decreased p-IκBα, but AgIV treatment suppressed this. In addition, AgIV synergized with carboplatin to suppress tumor xenograft growth of PC-3 cells, and decreased pAKT and p-p65 levels in vivo. In summary, our results suggested that AgIV enhanced carboplatin sensitivity in prostate cancer cell lines by suppressing AKT/NF-кB signaling, thus suppressed EMT induced by carboplatin. Our findings provided a new mechanism for AgIV in overcoming drug resistance of platinum-based chemotherapy, and suggested a potential combination therapy of AgIV and carboplatin in prostate cancer.
Effects of oral bovine lactoferrin on a mouse model of inflammation associated colon cancer
(Canadian Science Publishing, 2020-08-24) Tanaka, Hajime; Gunasekaran, Sivagami; Saleh, Dina Mourad; Alexander, William T.; Alexander, David B.; Ohara, Hirotaka; Tsuda, Hiroyuki
Patients with ulcerative colitis or colonic Crohn’s disease have a significantly increased risk of developing colorectal cancer. Bovine lactoferrin (bLF) reportedly inhibited the development of colon cancer in rats and mice, and in a placebo controlled trial, ingestion of bLF inhibited the growth of intestinal polyps. In addition, in a case study, a patient with Crohn’s disease was reported to have remained in remission for over 7 years while ingesting 1 g of bLF daily. Thus, bLF has an inhibitory effect on colon carcinogenesis, and it may also promote remission of Crohn’s disease. The purpose of this study was to investigate the effects of bLF in a mouse model of colorectal cancer related to irritable bowel disease (IBD). The mice were divided into 4 groups: (i) no treatment; (ii) treated with bLF only; (iii) treated with azoxymethane plus dextran sulfate sodium (AOM + DSS); and (iv) treated with AOM + DSS + bLF. AOM was used to initiate intestinal cancer, and DSS was used to induce IBD-like inflammation in the intestine of the C57BL/6 mice. At the end of the study, the mice treated with AOM + DSS + bLF had a better fecal score, fewer lesions in the colon, and less weight loss than the mice treated with AOM + DSS without bLF. However, there were no statistically significant differences between the two groups with respect to tumor burden.
Lactoferrin and hematoma detoxification after intracerebral hemorrhage
(Canadian Science Publishing, 2020-06-19) Zhao, Xiurong; Kruzel, Marian; Aronowski, Jaroslaw
In this minireview we discuss the role of lactoferrin (LTF) in detoxifying hematoma after intracerebral hemorrhage (ICH). Subsequent to ICH, neutrophils enter the ICH-affected brain, where they release various granule contents, including LTF. LTF is an iron-binding glycoprotein that binds Fe3+ with high affinity. Unlike other iron-binding proteins, LTF can retain Fe3+ at the low pH associated with inflamed tissue. LTF’s ability to sequester Fe3+ is of particular importance to ICH pathogenesis, because large quantities of free iron, which is pro-oxidative and pro-inflammatory, are generated in the ICH-affected brain owing to blood hemolysis. LTF delivered to ICH-affected brain, either as a therapeutic agent or through infiltrated polymorphonuclear neutrophils (cells containing high levels of LTF), could limit the pathogenesis of ICH. LTF is a protein with a high isoelectric point (8.7), a property that enables it to bind to negatively-charged apoptotic cells or proteins. Here, LTF could act as a bridging molecule that couples the apoptotic cells to LTF receptors on the cellular membranes of microglia/macrophages to facilitate the efferocytosis/erythrophagocytosis of apoptotic cells and damaged red blood cells. Thus, by virtue of sequestrating iron and facilitating efferocytosis, LTF may contribute to hematoma detoxification and hematoma/inflammation resolution after ICH.
Evidence from systematic reviews of randomized trials on enteral lactoferrin supplementation in preterm neonates
(Canadian Science Publishing, 2020-07-03) Pammi, Mohan; Preidis, Geoffrey A.; Tarnow-Mordi, William O.
In this commentary, we summarize the current evidence from randomized controlled trials on enteral lactoferrin supplementation in preterm neonates. Our recently completed systematic review includes 12 randomized controlled trials performed all over the world. Our meta-analysis suggests clinical benefit in decreasing late-onset sepsis, late-onset fungal sepsis, length of stay in the hospital and urinary tract infections. There were no adverse effects. There was no statistically significant decrease in necrotizing enterocolitis, mortality or neurodevelopmental impairment in lactoferrin supplemented preterm infants. There was significant statistical heterogeneity in the effects of lactoferrin on late-onset sepsis between larger and smaller studies, which may reflect either small study biases, differences in the effectiveness, dose or duration of supplemental lactoferrin products, or differences in underlying population risk, or any or all of these.

Browse

Recent Submissions