Gabriele Froemming | Universiti Malaysia Sarawak (UNIMAS) (original) (raw)

Papers by Gabriele Froemming

Zenodo (CERN European Organization for Nuclear Research), Dec 26, 2012

Supplementation of palm vitamin E has been reported to prevent loss of bone density in ovariectom... more Supplementation of palm vitamin E has been reported to prevent loss of bone density in ovariectomised female rats. The mechanism by which palm vitamin E exerts these effects is still unknown. We hypothesized that palm vitamin E may act by preventing the protein expression changes. Two dimensional poly acyrilamide gel electrophoresis (2-D PAGE) and PD Quest software genomic solutions Investigator (proteomics) was used to analyze the differential protein expression profile in femoral and humeri bones harvested from three groups of rats; sham-operated rats (SO), ovariectomised rats (Ovx) and ovariectomised rats supplemented for 2 months with palm vitamin E. The results showed that there were over 300 valued spot on each of the groups PVE and OVX as compared to about 200 in SO. Comparison between the differential protein expression between OVX and PVE groups showed that ten spots were down-regulated in OVX but up-regulated in PVE. The ten differential spots were separately named P1-P10. The identification and understanding of the pathway of the differential protein expression among the groups is ongoing and may account for the molecular mechanism through which palm vitamin E exert its anti-osteoporotic effect.

Jurnal teknologi, Dec 13, 2017

Inhibition of telomerase activity has emerged as a promising strategy to combat cancer cells, esp... more Inhibition of telomerase activity has emerged as a promising strategy to combat cancer cells, especially ones with no specific molecular targets such as triple negative breast cancer (TNBC). Cisplatin, a chemotherapeutic drug, is causing DNA damage while apigenin, a plant-derived antioxidant, induces apoptosis in various cancer cell types. Little is known about their combined ability to inhibit telomerase activity in TNBC cells. In the current study, the effect of cisplatin in combination with apigenin was investigated with regards to telomerase activity and expression of the telomerase catalytic subunit hTERT as well as Heat Shock Protein 90 (Hsp90) and p23 in two types of TNBC (MDA-MB-231; HCC1806) and one non-tumorigenic (MCF10A) epithelial cell line. The results showed that the combined treatment of cisplatin and apigenin significantly down-regulated telomerase activity. The inhibition of telomerase activity was accompanied by a down-regulation of hTERT, Hsp90 and p23 at transcriptional and translational level in both TNBC cells, as compared to control cells. The results of the current study suggest that apigenin and cisplatin synergistically inhibit telomerase activity by downregulating the enzyme's catalytic subunit. However, the exact roles of Hsp90 and p23 in the regulation of telomerase activity requires further investigation as they seem to be TNBC subtype-specific.

international food research journal, Jun 30, 2022

The present work evaluated the protective effects of Spirulina against the bone fragility caused ... more The present work evaluated the protective effects of Spirulina against the bone fragility caused by Garcinia cambogia in high-fat diet induced obese rats. High-fat diet and high-fat emulsion (HFD+HFE) were administered via oral gavage to 30 six-week-old female Sprague Dawley rats for six weeks to induce obesity, except for a normal group (n = 6). Following four weeks of treatment, the diet-induced obese groups were orally administered, daily, with (1) G. cambogia (GC); (2) Spirulina (S); and (3) G. cambogia + Spirulina (GC+S). The normal and obese control groups were treated with equal volumes of 0.9% saline water. It was found that GC significantly decreased body mass index (BMI) below the obese range (0.68 g/cm 2). Additionally, GC altered bone mineral density (BMD), increased phosphate and calcium levels, and decreased maximum force and mineral apposition rates (MAR) as compared to the obese control group (p < 0.05). Bone fragility caused by GC was confirmed by the decrease in bone formation marker osteocalcin (OCN), as well as an increase in bone resorption markers receptor activator of nuclear factor kappa-B ligand (RANKL) and tartrate-resistant acid phosphatase type 5b (TRAP5b) as compared to the obese control group. Spirulina also decreased the BMI of the obese rats. Spirulina also increased blood bone markers, BMD, maximum force, and Young's modulus. Rats supplemented with GC+S demonstrated higher double-labelled surface (dLS/BS) and MAR as compared to those in the GC group (p < 0.05). Meanwhile, the S group demonstrated improvement in all dynamic histomorphometric indices. S and GC+S groups demonstrated bone formation upregulation and bone resorption downregulation, thus indicating a bone protective effect of Spirulina. Overall, GC treatment led to bone fragility. GC+S treatment significantly augmented bone formation and mineralisation in obese rats as compared to the GC treatment alone. Rats in the S group demonstrated effective weight reduction while showing no destructive effects on the bone.

Journal of Traditional and Complementary Medicine, Aug 1, 2021

Spirulina (blue-green algae) contains a wide range of nutrients with medicinal properties which i... more Spirulina (blue-green algae) contains a wide range of nutrients with medicinal properties which include β-carotene, chromium, and moderate amounts of vitamins B12. This study aims to determine the preventive effect of spirulina against bone fragility linked to type 2 diabetes mellitus. Thirty Sprague-Dawley rats were divided into five groups (n = 6) and diabetes was induced using streptozocin. Rats with a plasma glucose level of 10 mmol/L and above were orally treated for twelve weeks with either a single dose of spirulina, metformin, or a combined dose of spirulina + metformin per day. After the treatment, blood and bones were taken for biochemical analysis, three-dimensional imaging, 3-point biomechanical analysis, histology imaging and gene expression using qPCR. Results showed that diabetes induction and treatment with metformin caused destruction in the trabecular microarchitecture of the femur bone, reduction in serum bone marker and expression of bone formation marker genes in the experimental rats. Spirulina supplementation showed improved trabecular microarchitecture with a denser trabecular network, increased 25-OH vitamin D levels, and lowered the level of phosphate and calcium in the serum. Biomechanical tests revealed increased maximum force, stress strain, young modulus and histology images showed improvement in regular mesh and an increase in osteoblasts and osteocytes. There was an increase in the expression of bone formation marker osteocalcin. The results suggest that spirulina supplementation was more effective at improving bone structural strength and stiffness in diabetic rats compared to metformin. Spirulina may be able to prevent T2DM-related brittle bone, lowering the risk of fracture.

Current Pharmaceutical Biotechnology, Feb 1, 2021

Background: Diabetes Mellitus (DM) is characterized by hyperglycemia (high blood glucose levels) ... more Background: Diabetes Mellitus (DM) is characterized by hyperglycemia (high blood glucose levels) which is due to the destruction of insulin-producing β-cells in the islets of Langerhans in the pancreas. It is associated with oxidative and endoplasmic reticulum stress. The plant alkaloid Palmatine has been previously reported to possess antidiabetic and antioxidant properties as well as other protective properties against kidney and liver tissue damage. Objective: Here, we investigated the ability of Palmatine to reduce the up-regulation of chaperone proteins Glucose Regulatory Protein 78 (GRP78), and Calreticulin (CALR) protein in a Streptozotocin (STZ)-induced diabetic rat model. Methods: Streptozotocin (STZ) induced diabetes in Sprague Dawley rats treated with 2mg/kg of Palmatine for 12 weeks after the elevation of plasma glucose levels above 11mmol/L post-STZ administration. Proteins were extracted from the pancreas after treatment and Two-Dimensional gel electrophoresis (2-DE), PDQuest 2-D analysis software genomic solutions and mass spectrometer were used to analyze differentially expressed protein. Mass Spectrometry (MS/MS), Multidimensional Protein Identification Technology (MudPIT) was used for protein identification. Results: There was an up-regulation of the expression of chaperone proteins CALR and GRP78 and down-regulation of the expression of antioxidant and protection proteins peroxidoxin 4 (Prdx4), protein disulfide isomerase (PDIA2/3), Glutathione-S-Transferase (GSTs), and Serum Albumin (ALB) in non-diabetic rats. Palmatine treatment down-regulated the expression of chaperone proteins CALR and GRP78 and up-regulated the expression of Prdx4, PDIA2/3, GST, and ALB. Conclusion: Palmatine may have activated antioxidant proteins, which protected the cells against reactive oxygen species and endoplasmic stress. The result is in consonance with our previous report on Palmatine.

Gene inactivation by promoter hypermethylation is a common occurrence in the development of vario... more Gene inactivation by promoter hypermethylation is a common occurrence in the development of various human cancers including oral cancer. Previous evidences observed that DNA methylation play a vital role in the carcinogenesis of oral cancer. The aim of this study was to analyze methylation status and protein expression of RRM2 in oral cancer. Archival tissues of oral cancer and healthy mucosa tissues were retrieved for the study. The methylation status of RRM2 was examined by methylation specific polymerase chain reaction and its protein expression was measured by immunohistochemistry. In the present study, frequency of aberrant methylation of RRM2 was 80% (n=32) in tumour tissues, whereas such methylation status was negatively detected in normal mucosa. In addition, 20 % (n=8) for RRM2 immunoreactivity was revealed in tumour tissues. In tumour tissues, RRM2 promoter hypermethylation was frequently associated with its reduced protein expression. Thus, epigenetic inactivation of RRM2 through promoter hypermethylation may be important in the oral cancer progression and assessment of RRM2 methylation status in oral cancer may become a potential biomarker for early detection in oral cancer.

Fundamental & Clinical Pharmacology

Streptozotocin (STZ) is a broad‐spectrum antibiotic that is toxic to the insulin‐producing beta c... more Streptozotocin (STZ) is a broad‐spectrum antibiotic that is toxic to the insulin‐producing beta cells of the pancreatic islets. STZ is currently used clinically for the treatment of metastatic islet cell carcinoma of the pancreas and the induction of diabetes mellitus (DM) in rodents. So far, there has been no previous research to show that STZ injection in rodents causes insulin resistance in type 2 diabetes mellitus (T2DM). The purpose of this study was to determine if rats (Sprague–Dawley) developed type 2 diabetes mellitus (insulin resistance) after 72 h of intraperitoneal administration of 50 mg/kg STZ. Rats with fasting blood glucose levels above 11.0 mM, 72 h post‐STZ induction, were used. The body weight and plasma glucose levels were measured every week throughout the 60‐day treatment period. The plasma, liver, kidney, pancreas, and smooth muscle cells were harvested for antioxidant, biochemical analysis, histology, and gene expression studies. The results revealed that STZ...

Medicinal Plants - International Journal of Phytomedicines and Related Industries

The FASEB Journal, 2020

BackgroundPalmatine is a protoberberine alkaloid which identified to be the bioactive compound pr... more BackgroundPalmatine is a protoberberine alkaloid which identified to be the bioactive compound present in stem extract of Cosininum Fenestratum plant. Our previous research have reported the plasma glucose lowering activity of Palmatine and its effect on liver, kidney and antioxidant enzymes parameters in STZ induced diabetic rat model. We also reported that the molecular mechanism of action of palmatine insulin release is through activation insulin‐dependent pathway in vivo and in vitro.ObjectiveThe focus of this study was to determine the effect of Palmatine on insulin dependent signaling pathway in insulin resistance rat skeletal muscle ex‐vivo.MethodNormal Male SD rats (180–200g) were sacrificed and skeletal muscles were harvested. The smaller size skeletal muscles from rats were mounted in the Krebs‐Henseleit buffer (KHB) buffer to maintain the resting position. The tissues were then incubated at 37°C under 95% O2‐ 5%CO2 in Glucose free KHB containing 01% BSA and 1mM pyruvate f...

Journal of Fundamental and Applied Sciences, 2018

Oral cancer is the sixth most common cancer worldwide and Malaysia ranked 14 in the world for ora... more Oral cancer is the sixth most common cancer worldwide and Malaysia ranked 14 in the world for oral cancer incidence. Despite recent advancement in treatment and survival rates for oral cancer patients have not improved significantly over the past decades. Ganodermalucidum has medicine for prevention and treatment of various diseas towards oral cancer cell line was determined in this study using in vitro model study. After 24 h treatment with G. lucidum, the IC Thus, this study shows a prelimi cancer cell line, ORL-48T.

Asian Pacific Journal of Cancer Prevention, 2014

Background: Promoter hypermethylation leads to altered gene functions and may result in malignant... more Background: Promoter hypermethylation leads to altered gene functions and may result in malignant cellular transformation. Thus, identification of biomarkers for hypermethylated genes could be useful for diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). Objectives: To screen hypermethylated genes with a microarray approach and to validate selected hypermethylated genes with the methylation-specific polymerase chain reaction (MSPCR). Materials and Methods: Genome-wide analysis of normal oral mucosa and OSCC tissues was conducted using the Illumina methylation microarray. The specified differential genes were selected and hypermethylation status was further verified with an independent cohort sample of OSCC samples. Candidate genes were screened using microarray assay and run by MSPCR analysis. Results: TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential hypermethylation status. Conclusions: Our microarray screening and MSPCR approaches revealed that the signature candidates of differentially hypermethylated genes may possibly become potential biomarkers which would be useful for diagnostic, prognostic and therapeutic targets of OSCC in the near future.

Asian Pacific Journal of Cancer Prevention, 2016

Background: Promoter hypermethylation is a frequent epigenetic mechanism for gene transcription r... more Background: Promoter hypermethylation is a frequent epigenetic mechanism for gene transcription repression in cancer and is one of the hallmarks of the disease. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) contributes to cell contact-mediated communication. Dysregulation of promoter methylation has been reported in various cancers. Objectives: The objectives of this study were to investigate the CELSR3 hypermethylation level in oral squamous cell carcinomas (OSCCs) using methylation-sensitive high-resolution melting analysis (MS-HRM) and to correlate CELSR3 methylation with patient demographic and clinicopathological parameters. Materials and Methods: Frozen tissue samples of healthy subjects' normal mucosa and OSCCs were examined with regard to their methylation levels of the CELSR3 gene using MS-HRM. Results: MS-HRM analysis revealed a high methylation level of CELSR3 in 86% of OSCC cases. Significant correlations were found between CELSR3 quantitative methylation levels with patient ethnicity (P=0.005), age (P=0.024) and pathological stages (P=0.004). A moderate positive correlation between CELSR3 and patient age was also evident (R=0.444, P=0.001). Conclusions: CELSR3 promoter hypermethylation may be an important mechanism involved in oral carcinogenesis. It may thus be used as a biomarker in OSCC prognostication.

Asia Pacific Journal of Molecular Biology and Biotechnology

Nisin, a known food preservative, has antimicrobial and anticancer properties. Nisin is a polycyc... more Nisin, a known food preservative, has antimicrobial and anticancer properties. Nisin is a polycyclic polypeptide with five internal rings; a feature that strongly influence the choice of solvent to attain effectivity of the compound for all cell culture experiments. Previous studies used a number of solvents but comparison between these to identify the best solvent have not been reported. Aim: To investigate the effect of nisin ZP (NZP) when dissolved in four different solvents on the viability of MG63 osteosarcoma cells. Materials and methods: MG-63 cells were incubated overnight at 37°C, 5% CO2 and treated with increasing concentration of dimethyl sulfoxide (DMSO), methanol and acetic acid to observe the cytotoxic effects of these chemicals onto the cells via MTS assay. NZP was then dissolved in distilled water and the three solvents in increasing concentrations and applied to the cultured cells. Cell viability and morphology were documented. Results: Acetic acid, DMSO and methano...

Malaysian Journal of Microscopy

Materials Science and Engineering: C, 2015

Life

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY