Phaleria macrocarpa (Scheff.) Boerl fruit aqueous extract enhances LDL receptor and PCSK9 expression in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Phaleria macrocarpa (Scheff.) Boerl (Pm) has been shown to reduce cholesterol level in vitro and in vivo experiment. AIM OF THE STUDY: This study investigated the effects of Pm fruit on weight control and mechanistic basis of its anti-hypercholesterolemic effect in both in vivo and in vitro. MATERIALS AND METHOD: In the in vivo study, thirty six male Sprague Dawley were randomized to six groups. Five groups were induced into hypercholesterolemia by giving 3% cholesterol enriched-diet for 52 days while one group acted as control. The rats were then treated with Pm extract (0, 20, 30 and 40 mg/ml) or simvastatin for 84 days. The following parameters were determined: (1) body weight, (2) blood lipid profile (total cholesterol, triglyceride, HDL and LDL) and (3) hepatic LDL receptor (160 kDa and 120 kDa) and PCSK9 proteins. In the in vitro study, HepG2 cells were cultured in serum-free RPMI supplemented with 0.2% BSA with or without LDL and in the presence of Pm extract (0, 0.1, 2, 40 and 1,000 μg/ml) or simvastatin (4.60 μg/ml) for 24h. The abundance of both LDL receptor and PCSK9 proteins and mRNA were investigated. RESULTS: Pm extract significantly (P<0.05) reduced body weight gain, total cholesterol, triglycerides, HDL LDL levels and upregulated hepatic LDL receptor as well as PCSK9 proteins of hypercholesterolemic rats. These results were supported by studies in HepG2 cells whereby Pm extract also significantly upregulated both LDL receptor and PCSK9 at protein and mRNA levels. CONCLUSION: This study enhances the potential usage of Pm fruit for controlling the body weight of obese people and for treating hypercholesterolemia

In vivo and in vitro effects of phaleria macrocarpa (scheff.) boerl on low density lipoprotein and pcsk9 expression

Phaleria macrocarpa.iPm) fruit is traditionally used to treat high cholesterol level. .However itsanti-hypercholesterolemic property is still unknown. LDL receptor is a ligand that involves in the cholesterol metabolism by taking in LDL which has -high proportion of cholesterol whereas PCSK9 is a protein that mediates the degradation of LDL receptor. This study investigat-ed the effects of Pm fruit aqueous extract on weight control and mechanistic basis of its anti-hypercholesterolemic effect in both in vivo and in vitro conditions. In vivo study, 36 male Sprague dawley rats were randomized to 6 groups. 5 groups were given 3% (v/v) cholesterol enriched-diet for 52 days to induced to become hypercholesterolemia, followed by Pm fruit aqueous extract (0, 20, 30 and 40 mg -extract/kg bw) or .simvastatin (40 mg/kg) treatment for 84 days. The sixth group was used as a negative controL The effects of Pm fruit aqueous extr-acttreatment were determined on the following parameters: 1) body weight, 2) liver weight 3) liver weight-to-body weight ratio 4) blood lipid profiles (TC, TG: HDL and LDL) and 5) expression level of hepatic LDL receptor (160 kDa and 120 kDa) and PCSK9 proteins. Pm fruit aqueous extract significantly (p<0.05) reduced body weight gain but tends to reduce liver weight and liver weight-to-body weight ratio. As for the blood lipid profiles, 20 mgextract! kg bw of Pm significantly (P<0.05) reduced TC (1.54 mmol/L), TG (0.38 mmol/L), HDL (0.68 mmol/L) and LDL (0.94 mmollL) -whereas 30 mg extract! kg bw of Pm significantly (p<0.05) reduced TC (1-.55 mmol/L), TG (0.33 mmol/L) and LDL (0.93 mmol/L) as compared I to the untreated hypercholesterolemic group [TC (2.4 mmol/L), TG (1.13 mmol/L), HDL JO.94 mmollL) and LDL-(1.51 mmol/Lj], 40 mg. extract! kg bw of Pm signiIicantly-(p<0.05) reduced TC (1.85 mmol/L) and LDL (1.03 mmol/L). On the other hand, 20 mg extract! kg bw of Pm significantly (P<0.05Y increased LDL receptor and PCSK9 proteins by l-fold whereas 30 and 40 mg extract! kg bw of Pm had no effect on LDL receptor and PCSK9. Effect of Pm fruit aqueous extract in- in vivo model was then further analyzed in in vitro study. In vitro study, HepG2 cells were cultured in serum-free RPM! 1640, supplemented with 0.2% BSA with or without LDL (200 llM) and in the presence of Pm fruit aqueous extract (0, 0.1,2,40 and 1000 ug/ml) or simvastatin (10 llM) for 24 hours. The abundance of both LDL receptor (1-60 kDa) and -PCSK9 proteins and mRNA were then investigated. Similar to the in vivo study, Pm fruit aqueous extract was found to have increased -LDL receptor and PCSK9 proteins by l-fold in HepG2 cells with significant increment (P<0.05) at the concentration of 0.1 ug/ml. Besides that, Pm fruit aqueous extract at the concentration of 0.1 ug/ml also significantly (P<0.05) increased both LDL receptor and PCSK9 mRNA transcripts, comparable to simvastatin treated group. These study indicated that Pm fruit aqueous extract reduces body weight gain, liver weight, liver weight-to-body weight ratio and exhibited anti-hypercholesterolemic effect by reducing blood lipid profile of hypercholesterolemic rats and upregulating LDL receptor and PCSK9 at both protein and rnRNA level

Nucleotide probes for detection of candida species.

The distinctive sequences of the Candida species internal transcribed spacer 2 regions are biotin-labeled and amplified for the subsequent species identification. Oligonucleotides which used as probes for identifying the Candida species are described. These oligonucleotides are useful in methods for the detection, identification, differentiation and diagnosis of Candida infection in a sample or subject

β-Lactam resistance in upper respiratory tract pathogens isolated from a tertiary hospital in Malaysia

The rise of antimicrobial resistance (AMR) among clinically important bacteria, including respiratory pathogens, is a growing concern for public health worldwide. Common causative bacteria for upper respiratory tract infections (URTIs) include Streptococcus pneumoniae and Haemophilus influenzae, and sometimes Staphylococcus aureus. We assessed the β-lactam resistant trends and mechanisms of 150 URTI strains isolated in a tertiary care hospital in Kuala Lumpur Malaysia. High rates of non-susceptibility to penicillin G (38%), amoxicillin-clavulanate (48%), imipenem (60%), and meropenem (56%) were observed in S. pneumoniae. Frequent mutations at STMK and SRNVP motifs in PBP1a (41%), SSNT motif in PBP2b (32%), and STMK and LKSG motifs in PBP2x (41%) were observed in S. pneumoniae. H. influenzae remained highly susceptible to most β-lactams, except for ampicillin. Approximately half of the ampicillin non-susceptible H. influenzae harboured PBP3 mutations (56%) and only blaTEM was detected in the ampicillin-resistant strains (47%). Methicillin-susceptible S. aureus (MSSA) strains were mostly resistant to penicillin G (92%), with at least two-fold higher median minimum inhibitory concentrations (MIC) for all penicillin antibiotics (except ticarcillin) compared to S. pneumoniae and H. influenzae. Almost all URTI strains (88–100%) were susceptible to cefcapene and flomoxef. Overall, β-lactam antibiotics except penicillins remained largely effective against URTI pathogens in this region

Recurrent candidaemia in a neonate with Hirschsprung’s disease: fluconazole resistance and genetic relatedness of eight Candida tropicalis isolates

The incidence of candidaemia among immunocompromised patients in Malaysia is increasing at an alarming rate. Isolation of clinical strains that are resistant to fluconazole has also risen markedly. We report here the repeated isolation of Candida tropicalis from the blood of a neonatal patient with Hirschsprung's disease. In vitro fluconazole susceptibility tests of the eight isolates obtained at different time points showed that seven of the isolates were resistant and one isolate was scored as susceptible dose-dependent. Random amplification of polymorphic DNA fingerprinting of the isolates using three primers and subsequent phylogenetic analysis revealed that these isolates were highly similar strains having minor genetic divergence, with a mean pairwise similarity coefficient of 0·893±0·041. The source of the infectious agent was thought to be the central venous catheter, as culture of its tip produced fluconazole-resistant C. tropicalis. This study demonstrates the utility of applying molecular epidemiology techniques to complement traditional mycological culture and drug susceptibility tests for accurate and appropriate management of recurrent candidaemia and highlights the need for newer antifungals that can combat the emergence of fluconazole-resistant C. tropicalis strains

Genomic comparison and phenotypic profiling of small colony variants of Burkholderia pseudomallei

Burkholderia pseudomallei (B. pseudomallei) is an intracellular pathogen that causes melioidosis, a life-threatening infection in humans. The bacterium is able to form small colony variants (SCVs) as part of the adaptive features in response to environmental stress. In this study, we characterize the genomic characteristics, antimicrobial resistance (AMR), and metabolic phenotypes of B. pseudomallei SCV and wild type (WT) strains. Whole-genome sequence analysis was performed to characterize the genomic features of two SCVs (CS and OS) and their respective parental WT strains (CB and OB). Phylogenetic relationship between the four draft genomes in this study and 19 publicly available genomes from various countries was determined. The four draft genomes showed a close phylogenetic relationship with other genomes from Southeast Asia. Broth microdilution and phenotype microarray were conducted to determine the AMR profiles and metabolic features (carbon utilization, osmolytes sensitivity, and pH conditions) of all strains. The SCV strains exhibited identical AMR phenotype with their parental WT strains. A limited number of AMR-conferring genes were identified in the B. pseudomallei genomes. The SCVs and their respective parental WT strains generally shared similar carbon-utilization profiles, except for D,L-carnitine (CS), g-hydroxybutyric acid (OS), and succinamic acid (OS) which were utilized by the SCVs only. No difference was observed in the osmolytes sensitivity of all strains. In comparison, WT strains were more resistant to alkaline condition, while SCVs showed variable growth responses at higher acidity. Overall, the genomes of the colony morphology variants of B. pseudomallei were largely identical, and the phenotypic variations observed among the different morphotypes were strain-specific

Immunohistochemistry study of tumor vascular normalization and anti-angiogenic effects of sunitinib versus bevacizumab prior to dose-dense doxorubicin/cyclophosphamide chemotherapy in HER2-negative breast cancer

10.1007/s10549-021-06470-7BREAST CANCER RESEARCH AND TREATMENT1921131-14

Serial Tumor Molecular Profiling of Newly Diagnosed HER2-Negative Breast Cancers During Chemotherapy in Combination with Angiogenesis Inhibitors

10.1007/s11523-022-00886-xTARGETED ONCOLOGY173355-36

Genome-wide association study of Parkinson’s disease in East Asians

Genome-wide association studies (GWAS) on Parkinson’s disease (PD) have mostly been done in Europeans and Japanese. No study has been done in Han Chinese, which make up nearly a fifth of the world population. We conducted the first Han Chinese GWAS analysing a total of 22,729 subjects (5,125 PD cases and 17,604 controls) from Singapore, Hong Kong, Malaysia, Korea, mainland China and Taiwan. We performed imputation, merging and logistic regression analyses of 2,402,394 SNPs passing quality control filters in 779 PD cases, 13,227 controls, adjusted for the first three principal components. 90 SNPs with association P  1.45) on PD risk. Our results also demonstrate some differences in the genetic contribution to PD between Europeans and Asians. Further pan-ethnic meta-analysis with European GWAS cohorts may unravel new PD loci.NRF (Natl Research Foundation, S’pore)ASTAR (Agency for Sci., Tech. and Research, S’pore)NMRC (Natl Medical Research Council, S’pore)Accepted versio