Berberine Chloride and Hyperthermia Promote Osterix Expression and Suppress Cell Cycle Genes in Osteosarcoma Cells

Objectives: The aim of the current study was to investigate the effects of berberine chloride and various heat conditions on the gene expression of Osterix, RUNX-2, RANKL, CDK2, CDK4, IL-6 and IL-11. Methods:  Six groups of cells were treated with hyperthermia for 1 h: Two groups at mild, two at moderate and two at severe hyperthermia (39, 43 and 45°C respectively). Berberine chloride (80 µg/mL) was selected for treating one group of mild, moderate and severe hyperthermia (combination). All treated groups were recovered at 37°C for 24 h. Another exposure for hyperthermia (1 h) and recovery for 3 h at 37°C were applied. Results: The expression of Osterix was highly upregulated in all groups except in the severe hyperthermia and mild hyperthermia with berberine groups. Only the mild hyperthermia without berberine induced a slight increase in the expression of RUNX2, whereas severe hyperthermia alone suppressed the levels on a significant manner. Berberine alone was more effective in significantly up-regulating RANKL expression. On the other hand, CDK2 mRNA was downregulated in all groups. CDK4 showed a similar regulation in the mild hyperthermia group with control, but the expression was downregulated in the other groups, especially in severe hyperthermia the expression was significantly downregulated (p<0.5). IL-6 was upregulated highly and significantly in the group of berberine and all groups of combinations, whereas mild and moderate hyperthermia stimulated significant expression of IL-11 mRNA. Conclusion:  These results suggest that hyperthermia and berberine chloride can promote osteosarcoma cells differentiation and arrest cell-cycle

Human MG-63 osteosarcoma cells responses to long and short term hyper- and hypothermia stress

Hyper- and hypothermia are utilized as treatment modalities in cancer treatment or as a protection against ischemia-reperfusion induced cell damage. The under-lying mechanism of hyper- and hypothermia, on cell death in osteosarcoma cells are not well understood. The aim of this study is to investigate the short- and long-term effects of various severities of hyper- and hypothermia on osteoblast-like osteosarcoma cells (MG-63). MG-63 cells were treated with mild and severe hyper- and hypothermia for short, medium and long-term periods. Severe hypothermia and hyperthermia showed a time-dependent toxicity; hence viability was reduced in a significant manner at all time points and the cells were undergoing apoptosis. Mild hypothermia, on the other hand, showed a protective effect and long term exposure increased the cell viability. Severe hyperthermia induced significant DNA damage at all time points. Caspase 3/7 activity showed a significant increase at 1 h of severe hyperthermia and 72 h of severe hypothermia (p<0.05). Hsp90 expression was significantly increased at 72 h of mild hyperthermia (p<0.01), whereas Hsp70 showed a significant increase after 24 and 72 h (p<0.01 and p<0.001). Hsp27 mRNA was increased significantly at 24 h only under mild hyperthermia (p<0.01). In conclusion, hyperthermia especially severe hyperthermia induced cellular stress in MG-63 cells leading to apoptosis. Hypothermia, on the other hand caused severe cell stress only when the cells were challenged for a prolonged period with severe low temperatures

Mild hyperthermia (39°C) attenuates berberine chloride cytotoxicity against osteosarcoma cells

Many studies reported that antioxidants and dietary supplements increase tumour progress and reduce survival. Hyperthermia is an adjuvant treatment to sensitise cancer cells for radio- or chemotherapy. The current study was carried out to determine the effects of berberine chloride and hyperthermia on bone cancer cells. MG-63 osteosarcoma cells were treated with hyperthermia (39, 43 and 45°C, respectively) for 1 h. Then, the cells were treated with a low toxic dose of berberine chloride (80 μg/mL). After that, all treated groups were recovered at 37°C for 24 h. Finally, all groups were treated with hyperthermia (39, 43 and 45°C) for the second time (1 h) and were recovered for 3 h at 37°C. Cells exposed to hyperthermia without treatment of berberine chloride were used as hyperthermia control. Cells treated with 80 μg/mL of berberine at 37°C served as berberine control and cells incubated at 37°C were used as an untreated control. All treated groups showed significant apoptosis compared to the control group (p<0.05) except 39°C. On the other hand, mild hyperthermia treatment (39°C) resulted in a reduction of berberine-induced apoptosis (p<0.001). Severe and moderate hyperthermia did not show a significant increase in the rate of apoptosis compared to berberine treated cells. Mild hyperthermia treatment can effectively reduce berberine cytotoxicity and implying negative effects on cancer therapy

Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia

<p>Abstract</p> <p>Background</p> <p>Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.</p> <p>We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan). The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide substitutions, and by multiplex ligation-dependent probe amplification to detect large rearrangements.</p> <p>Results</p> <p>A total of 29 gene sequence variants were reported in 117(76.0%) of the studied subjects. Eight different mutations (1 large rearrangement, 1 short deletion, 5 missense mutations, and 1 splice site mutation), and 21 variants. Eight gene sequence variants were reported for the first time and they were noticed in familial hypercholesterolemic patients, but not in controls (p.Asp100Asp, p.Asp139His, p.Arg471Gly, c.1705+117 T>G, c.1186+41T>A, 1705+112C>G, Dup exon 12 and p.Trp666ProfsX45). The incidence of the p.Arg471Gly variant was 11%. Patients with pathogenic mutations were younger, had significantly higher incidences of cardiovascular disease, xanthomas, and family history of hyperlipidemia, together with significantly higher total cholesterol and low density lipoprotein levels than patients with non-pathogenic variants.</p> <p>Conclusions</p> <p>Twenty-nine gene sequence variants occurred among FH patients; those with predicted pathogenicity were associated with higher incidences of cardiovascular diseases, tendon xanthomas, and higher total and low density lipoprotein levels compared to the rest. These results provide preliminary information on the mutation spectrum of this gene among patients with FH in Malaysia.</p

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Lipid Profile Parameters in Malaysian Dyslipidemic Patients

The importance of serum lipids as cardiovascular risk factors is well recognized. However, most published studies have focused on western countries. The present study aimed to describe and analyze the lipid profile parameters in Malaysian dyslipidemic patients, and to identify concomitant clinical problems and risk factors associated with cardiovascular disease (CVD) among such patients. Methods: A retrospective record review was carried out at Hospital Universiti Sains Malaysia.The records were reviewed for 890 dyslipidemic patients who attended the hospital in 2007. Data were collected for age at time of presentation, sex, ethnicity, smoking status, pre-treatment lipid levels, and presence of associated illnesses. The study sample was classified according to the National Cholesterol Education Program Adult Treatment Panel III risk groups. Results: The mean (SD) values for total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides were 6.4 (1.3), 4.1 (1.3), 1.4 (0.5) and 1.9 (1.2) mmol/l, respectively. Less than half of study sample (43.1%) had coronary heart disease and coronary heart diseases equivalents, 24.3% were at moderate risk, and 32.6% were at low risk. Hypertension was present in 79.9% of the study sample, while 27.5% were diabetics. Cardiovascular disease was reported among 17.9%. Logistic regression revealed that family history of premature cardiovascular disease, higher age risk group; ethnicity and total cholesterol were predictors for the development of cardiovascular disease. Conclusion: The present review showed that dyslipidemic patients had high total cholesterol levels, according to National Cholesterol Education Program Adult Treatment Panel III guidelines. They were clinically diagnosed at middle age. Hypertension and diabetes were the commonest associated clinical problems. A large proportion of the patients were within the coronary heart disease or coronary heart disease risk equivalent group. Family history of premature cardiovascular disease, age, ethnicity, and total cholesterol are important risk factors for the development of cardiovascular disease in Malaysian dyslipidemic patients

Yusof Z. Lipid profile parameters in Malaysian dyslipidemic patients. The Kobe journal of the medical sciences

ABSTRACT Introduction The importance of serum lipids as cardiovascular risk factors is well recognized. However, most published studies have focused on western countries. The present study aimed to describe and analyze the lipid profile parameters in Malaysian dyslipidemic patients, and to identify concomitant clinical problems and risk factors associated with cardiovascular disease (CVD) among such patients. Methods: A retrospective record review was carried out at Hospital Universiti Sains Malaysia.The records were reviewed for 890 dyslipidemic patients who attended the hospital in 2007. Data were collected for age at time of presentation, sex, ethnicity, smoking status, pre-treatment lipid levels, and presence of associated illnesses. The study sample was classified according to the National Cholesterol Education Program Adult Treatment Panel III risk groups. Results: The mean (SD) values for total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides were 6.4 (1.3), 4.1 (1.3), 1.4 (0.5) and 1.9 (1.2) mmol/l, respectively. Less than half of study sample (43.1%) had coronary heart disease and coronary heart diseases equivalents, 24.3% were at moderate risk, and 32.6% were at low risk. Hypertension was present in 79.9% of the study sample, while 27.5% were diabetics. Cardiovascular disease was reported among 17.9%. Logistic regression revealed that family history of premature cardiovascular disease, higher age risk group; ethnicity and total cholesterol were predictors for the development of cardiovascular disease. Conclusion: The present review showed that dyslipidemic patients had high total cholesterol levels, according to National Cholesterol Education Program Adult Treatment Panel III guidelines. They were clinically diagnosed at middle age. Hypertension and diabetes Phone: +6019-9875767 Fax: +609-7676922 E-mail: [email protected] E38 LIPID PROFILES IN MALAYSIAN DYSLIPIDEMIC PATIENTS were the commonest associated clinical problems. A large proportion of the patients were within the coronary heart disease or coronary heart disease risk equivalent group. Family history of premature cardiovascular disease, age, ethnicity, and total cholesterol are important risk factors for the development of cardiovascular disease in Malaysian dyslipidemic patients

Undertreatment and Underachievement of LDL-C Target among Individuals with High and Very High Cardiovascular Risk in the Malaysian Community

Dyslipidaemia is a major cause of morbidity and mortality. The aims of this study are to determine the prevalence of dyslipidaemia subtypes, the proportions of lipid-lowering therapy (LLT) use, and the achievement of low-density lipoprotein cholesterol (LDL-C) treatment targets for high-risk (HR) and very high-risk (VHR) Malaysians. This cross-sectional study involves 5279 participants across 11 states in Malaysia. The data were obtained through a standardised questionnaire, anthropometric measurements, venous glucose and lipid profile. The participants with existing cardiovascular disease (CVD) or diabetes with at least one of the other major risk factors (smoking, hypertension or dyslipidaemia) were grouped into the VHR category. Other participants were risk-categorised using the Framingham General CVD Risk Score (FRS-CVD). The prevalence of elevated LDL-C, LLT use and LDL-C target were set according to respective risk categories. Pearson&rsquo;s chi-squared test was used to test the difference in the proportions. The mean &plusmn; standard deviation (SD) age was 41.1 &plusmn; 14.8 years, and 62.2% (3283/5279) of the group were females. Within the participant group, 51.5% were found to have elevated total cholesterol, 28.8% had low HDL-C, and 33.8% had high triglyceride. As for elevated LDL-C, 9.8% were in VHR, 8.6% in HR, 5.8% in MR and 34.9% in LR categories. Among the VHR group, 75.8% were not on LLT, and only 15.9% achieved the LDL-C target. As for the HR category, 87.7% were not on LLT, and only 16.1% achieved the LDL-C target. Dyslipidaemia is highly prevalent among Malaysians. The majority of VHR and HR participants were not on LLT and did not achieve LDL-C treatment targets. Proactive programs are warranted to combat dyslipidaemia-associated CVD events in these groups