Methods: Human neuroblastoma cells SH-SY5Y (as a neuronal model) and human glioblastoma cells T98G (as an astrocytic model), were treated with 100-500 µM PA, oleic acid (OA) or lauric acid (LA) for 24 h or 48 h, and their cell viability was assessed by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of stable overexpression of γ-synuclein (γ-syn), a neuronal protein recently recognized as a novel regulator of lipid handling in adipocytes, and transient overexpression of Parkinson's disease (PD) α-synuclein [α-syn; wild-type (wt) and its pathogenic mutants A53T, A30P and E46K] in SH-SY5Y and T98G cells, were also evaluated. The effects of co-treatment of PA with paraquat (PQ), a Parkinsonian pesticide, and leptin, a hormone involved in the brain-adipose axis, were also assessed. Cell death mode and cell cycle were analyzed by Annexin V/PI flow cytometry. Reactive oxygen species (ROS) level was determined using 2',7'-dichlorofluorescien diacetate (DCFH-DA) assay and lipid peroxidation level was determined using thiobarbituric acid reactive substances (TBARS) assay.
Results: MTT assay revealed dose- and time-dependent PA cytotoxicity on SH-SY5Y and T98G cells, but not OA and LA. The cytotoxicity was significantly lower in SH-SY5Y-γ-syn cells, while transient overexpression of wt α-syn or its PD mutants (A30P and E46K, but not A53T) modestly (but still significantly) rescued the cytotoxicity of PA in SH-SY5Y and T98G cells. Co-treatment of increasing concentrations of PQ exacerbated PA's neurotoxicity. Pre-treatment of leptin, an anti-apoptotic adipokine, did not successfully rescue SH-SY5Y cells from PA-induced cytotoxicity-suggesting a mechanism of PA-induced leptin resistance. Annexin V/PI flow cytometry analysis revealed PA-induced increase in percentages of cells in annexin V-positive/PI-negative quadrant (early apoptosis) and subG0-G1 fraction, accompanied by a decrease in G2-M phase cells. The PA-induced ROS production and lipid peroxidation was at greater extent in T98G as compared to that in SH-SY5Y.
Discussion: In conclusion, PA induces apoptosis by increasing oxidative stress in neurons and astrocytes. Taken together, the results suggest that HFD may cause neuronal and astrocytic damage, which indirectly proposes that CNS pathologies involving neuroinflammation and reactive gliosis could be prevented via the diet regimen.
Methods: EA cells were treated with conditioned media (CM) of LS 174T-γ-Syn or LS 174T-PrP, and their proliferation, invasion, migration, adhesion and ability to form angiogenic tubes were assessed using a range of biological assays. To investigate plausible background mechanisms in conferring the properties of EA cells above, nitrite oxide (NO) levels were measured and the expression of angiogenesis-related factors was assessed using a human angiogenesis antibody array.
Results: EA proliferation was significantly inhibited by LS 174T-PrP CM whereas its telomerase activity was reduced by CM of LS 174T-γ-Syn or LS 174T-PrP, as compared to EA incubated with LS 174T CM. Besides, LS 174T-γ-Syn CM or LS 174T-PrP CM inhibited EA invasion and migration in Boyden chamber assay. Furthermore, LS 174T-γ-Syn CM significantly inhibited EA migration in scratch wound assay. Gelatin zymography revealed reduced secretion of MMP-2 and MMP-9 by EA treated with LS 174T-γ-Syn CM or LS 174T-PrP CM. In addition, cell adhesion assay showed lesser LS 174T-γ-Syn or LS 174T-PrP cells adhered onto EA, as compared to LS 174T. In tube formation assay, LS 174T-γ-Syn CM or LS 174T-PrP CM induced EA tube formation. Increased NO secretion by EA treated with LS 174T-γ-Syn CM or LS 174T-PrP CM was also detected. Lastly, decreased expression of pro-angiogenic factors like CXCL16, IGFBP-2 and amphiregulin in LS 174T-γ-Syn CM or LS 174T-PrP CM was detected using the angiogenesis antibody array.
Discussion: These results suggest that overexpression of γ-Syn or PrPCcould possibly be involved in colorectal cancer-induced angiogenesis by inducing an endothelial proliferation-differentiation switch. NO could be the main factor in governing this switch, and modulation on the secretion patterns of angiogenesis-related proteins could be the strategy of colorectal cancer cells overexpressing γ-Syn or PrPCin ensuring this transition.
METHODS: This systematic review was performed conforming to preferred reporting items for systematic review and meta-analysis (PRISMA) model. Four different databases (PubMed, Science Direct, Scopus and Medline databases) as well as manual searching were adopted. Relevant studies from January 2000 till September 2021 were retrieved. Critical Appraisal Skills Programme (CASP) was used to assess the quality of the selected studies.
RESULTS: Out of 755 articles, only 14 which met the eligibility criteria were included. Six studies found that titanium dioxide nanotube (TNT) reduced oxidative stress and promoted osteoblastic activity through its effect on Wnt, mitogen-activated protein kinase (MAPK) and forkhead box protein O1 (FoxO1) signaling pathways. On the other hand, three studies confirmed that titanium dioxide nanoparticles (TiO2NPs) induce oxidative stress, reduce ostegenesis and impair antioxidant defense system as a significant negative correlation was found between decreased SIR3 protein level and increased superoxide (O2 •-). Moreover, five studies proved that titanium implant alloy enhances the generation of ROS and induces cytotoxicity of osteoblast cells via its effect on NOX pathway.
CONCLUSION: TiO2NPs stimulate a wide array of oxidative stress related pathways. Scientific evidence are in favor to support the use of TiO2 nanotube-coated titanium implants to reduce oxidative stress and promote osteogenesis in bone remodeling. To validate the cellular and molecular cross talk in bone remodeling of the present review, well-controlled clinical trials with a large sample size are required.
Methods: Experiments were conducted to determine the appropriate technique of corn-legume intercropping in conjunction with the supplemental use of chemical fertilizers, organic manure, and biofertilizers (BFs). Acetylene reduction assays (ARAs) were also performed on corn and soybean roots.
Results: Combining chemical fertilizers with chicken manure (CM) in a 50:50 ratio and applying 50% NPK+50% CM+BF produced fresh forage and dry matter (DM) yields that were similar to those produced in the 100% nitrogen (N), phosphorus (P), potassium (K) treatment. Among the lone fertilizer treatments, the inorganic fertilizer (100% NPK) treatment produced the highest DM yield (13.86 t/ha) of forage and outyielded the 100% CM (9.74 t/ha) treatment. However, when CM was combined with NPK, the resulting DM yield of forage (13.86 t/ha) was the same as that resulting from 100% NPK (13.68 t/ha). Compared with CM applications alone, combinations of NPK and CM applications resulted in increased plant height, crop growth rates (CGRs) and leaf area index (LAI), but the values of these parameters were similar to those resulting from 100% NPK application. Fertilizers in which the ratio was 50% CM+50% NPK or 50% CM+50% NPK+BF resulted in protein yields that were similar to those resulting from conventional fertilizers. Similarly, the CP content did not significantly differ between applications of the 100% NPK and 50% CM+50% NPK fertilizers. The use of BFs had no significant impact on improving either the yield or quality of forage fertilized with inorganic or organic fertilizer. Lactic acid responded differently to different fertilizer applications and was significantly higher in the fertilized plots than in the unfertilized plots. Compared with treatments of lone chemical and lone organic manure fertilizers, treatments involving applications of BF and a combination of BF and NPK or CM resulted in higher ARA values.
Discussion: There is no simple and easy approach to increase biological nitrogen fixation (BNF) in grain legumes grown as part of a cropping system under realistic farm field conditions. Overall, evidence recorded from this study proves that, compared with corn monocrops combined with CM and chemical fertilizers, corn-soybean intercrops could increase forage yields and quality, produce higher total protein yields, and reduce the need for protein supplements and chemical fertilizers.
METHODS: This study investigated the effects of two different training interventions based on individualized load velocity profiles (LVP) on maximal bench press strength (i.e., 1RM), maximum throwing velocity (TV), and skeletal muscle mass (SKMM). Twenty-two university handball players were randomly assigned to Group 1 (low-movement speed training) or Group 2 (high-movement speed training). Group 1 exercised with a bar speed of 0.75-0.96 m/s, which corresponds to a resistance of approximately 60% 1RM, whereas Group 2 trained at 1.03-1.20 m/s, corresponding to a resistance of approximately 40% 1RM. Both groups exercised three times a week for five weeks, with strength and throwing tests performed at baseline and post-intervention.
RESULTS: A two-way repeated measures ANOVA was applied, and the results showed the interaction between group and time was not statistically significant for SKMM (p = 0.537), 1RM (p = 0.883), or TV (p = 0.774). However, both groups significantly improved after the five weeks of training: SKMM (3.1% and 3.5%, p
Methods: The sample consisted of 11 cone-beam computed tomography (CBCT) scans data, evaluated using the Invivo5 (Anatomage) and Romexis (version 3.8.2.R, Planmeca) software which afford image reconstruction, and airway analysis. The measurements were done twice with one week gap between the two measurements. The measurement obtained was analyzed with t-tests and intraclass correlation coefficient (ICC), with confidence intervals (CI) was set at 95%.
Results: From the analysis, the mean reading of volume and minimum area is not significantly different between Invivo5 and Romexis. Excellent intrarater reliability values were found for the both measurement on both software, with ICC values ranging from 0.940 to 0.998.
Discussion: The results suggested that both software can be used in further studies to investigate upper airway, thereby contributing to the diagnosis of upper airway obstructions.
Methods: A retrospective analysis was performed on 946 patients with CRC diagnosed from 1997 to 2017 at Universiti Kebangsaan Malaysia Medical Centre. The time trend was assessed by dividing the two decades into four 5-year periods. The mean age-standardized and age-specific incidence rates were calculated by using the 5-year cumulative population of Kuala Lumpur and World Health Organization standard population. The mean incidence was expressed per 100,000 person-years.
Results: After a stable (all age groups) CRC incidence rate during the first decade (3.00 per 100,000 and 3.85 per 100,000), it sharply increased to 6.12 per 100,000 in the 2008-2012 period before decreasing to 4.54 per 100,000 in the 2013-2017 period. The CRC incidence trend in later-onset CRC showed a decrease in the 2013-2017 period. Contrariwise, for age groups of 40-44 and 45-49 years, the trends showed an increase in the latter 15 years of the study period (40-44 years: 1.44 to 1.92 to 2.3 per 100,000; 45-49 years: 2.87 to 2.94 to 4.01 per 100,000). Malays' EOCRC incidence rate increased from 2008-2012 to 2013-2017 for both the age groups 40-44 years (1.46 to 2.89 per 100,000) and 45-49 years (2.73 to 6.51 per 100,000). Nearly one-fifth of EOCRC cases were diagnosed at an advanced stage (Dukes D: 19.9%), and the majority of them had rectal cancer (72.8%).
Conclusion: The incidence of EOCRC increased over the period 1997-2017; the patients were predominantly Malays, diagnosed at a later stage, and with cancer commonly localized in the rectal region. All the relevant stakeholders need to work on the management and prevention of CRC in Malaysia.
Method: Thirty-five full-length pk41 sequences from clinical isolates of Malaysia along with four laboratory lines (along with H-strain) were downloaded from public databases. For comparative analysis between species, orthologous P41 genes from P. falciparum, P. vivax, P. coatneyi and P. cynomolgi were also downloaded. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 software. Phylogenetic relationships between Pk41 genes were determined using MEGA 5.0 software.
Results: Analysis of 39 full-length pk41 sequences along with the H-strain identified 36 SNPs (20 non-synonymous and 16 synonymous substitutions) resulting in 31 haplotypes. Nucleotide diversity across the full-length gene was low and was similar to its ortholog in P. vivax; pv41. Domain-wise amino acid analysis of the two s48/45 domains indicated low level of polymorphisms for both the domains, and the glutamic acid rich region had extensive size variations. In the central domain, upstream to the glutamate rich region, a unique two to six (K-E)n repeat region was identified within the clinical isolates. Overall, the pk41 genes were indicative of negative/purifying selection due to functional constraints. Domain-wise analysis of the s48/45 domains also indicated purifying selection. However, analysis of Tajima's D across the genes identified non-synonymous SNPs in the s48/45 domain II with high positive values indicating possible epitope binding regions. All the 6-cysteine residues within the s48/45 domains were conserved within the clinical isolates indicating functional conservation of these regions. Phylogenetic analysis of full-length pk41 genes indicated geographical clustering and identified three subpopulations of P. knowlesi; one originating in the laboratory lines and two originating from Sarawak, Malaysian Borneo.
Conclusion: This is the first study to report on the polymorphism and natural selection of pk41 genes from clinical isolates of Malaysia. The results reveal that there is low level of polymorphism in both s48/45 domains, indicating that this antigen could be a potential vaccine target. However, genetic and molecular immunology studies involving higher number of samples from various parts of Malaysia would be necessary to validate this antigen's candidacy as a vaccine target for P. knowlesi.
Method: A total of 89 methicillin-resistant S. aureus (MRSA) [pus (n = 55), blood (n = 27), respiratory (n = 5), eye (n = 2)] isolates and 109 methicillin-susceptible S. aureus (MSSA) [pus (n = 79), blood (n = 24), respiratory (n = 3), eye (n = 2) and urine (n = 1)] isolates were subjected to spa typing with sequences analysed using BioNumerics version 7.
Results: The spa sequence was successfully amplified from 77.8% of the strains (154/198) and 47 known spa types were detected. The distribution of known spa types in MRSA (36.2%, 17/47) was less diverse than in MSSA (70.2%, 33/47). The most predominant spa types were t032 (50%) in MRSA, and t127 (19%) and t091 (16.7%) in MSSA, respectively. spa type t091 in MSSA was significantly associated with skin and soft tissue infections (p = 0.0199).
Conclusion: The previously uncommon spa type t032 was detected in the Malaysian MRSA strains, which also corresponded to the most common spa type in Europe and Australia, and has replaced the dominant spa type t037 which was reported in Malaysia in 2010.