METHODS: The prevalence of G6PD deficiency among 408 Thai participants diagnosed with malaria by microscopy (71), and malaria-negative controls (337), was assessed using a phenotypic test based on water-soluble tetrazolium salts. High-resolution melting (HRM) curve analysis was developed from a previous study to enable the detection of 15 common missense, synonymous and intronic G6PD mutations in Asian populations. The identified mutations were subjected to biochemical and structural characterisation to understand the molecular mechanisms underlying enzyme deficiency.
RESULTS: Based on phenotypic testing, the prevalence of G6PD deficiency (T) and intronic (c.1365-13T>C and c.486-34delT) mutations was detected with intermediate to normal enzyme activity. The double missense mutations were less catalytically active than their corresponding single missense mutations, resulting in severe enzyme deficiency. While the mutations had a minor effect on binding affinity, structural instability was a key contributor to the enzyme deficiency observed in G6PD-deficient individuals.
CONCLUSIONS: With varying degrees of enzyme deficiency, G6PD genotyping can be used as a complement to phenotypic screening to identify those who are eligible for 8-aminoquinolines. The information gained from this study could be useful for management and treatment of malaria, as well as for the prevention of unanticipated reactions to certain medications and foods in the studied population.
MATERIALS AND METHODS: The different primer sets were developed using bioinformatics software DNASTAR. The E. coli cells were used for recombinant protein expression.
RESULTS: The NiV 'G' region primers were designed and amplified for 1 kb fragment and cloned. The NiV 'G' fragments were sub-cloned in pET-28(+) B and pGEX-5x-1. Recombinant protein thus obtained in soluble form in both the cases was essayed using western blot. The result showed the protein expression yield was more in pET-28(+) B with low stability and vice versa for pGEX-5x-1.
CONCLUSION: The antibodies raised from the protein can be used as diagnostic reagent for detection of NiV. Thus, a new diagnostic technique can be industrialized.
OBJECTIVE: To determine the prevalence and sociodemographic factors predicting high-risk HPV infection in Malaysia based on a public, community-based cervical cancer screening registry targeting women at risk of getting HPV infection.
METHODS: The study used data from the Malaysian cervical cancer screening registry established by the Family Health Development Division from 2019 to 2021. The registry recorded sociodemographic data, HPV test details and results of eligible women who underwent HPV screening at public primary healthcare facilities. A vaginal sample (via self-sampling or assisted by a healthcare provider) was used for DNA extraction for HPV detection and genotyping. Registry data were extracted and analysed to determine prevalence estimates of high-risk HPV infection. Multifactorial logistic regression analysis was conducted to determine predictors of high-risk HPV infection. All analyses were performed using Stata version 14.
RESULTS: The programme screened a total of 36,738 women during the study period. Women who attended the screening programme were mainly from urban areas, aged 30-39 years, and of Malay ethnicity. The prevalence of high-risk HPV infection was 4.53% among women screened, with the yearly prevalence ranging from 4.27 to 4.80%. A higher prevalence was observed among urban settling women, those aged 30-49 years, those of Indian ethnicity, and those without children. The results from logistic regression showed that women from urban areas, lower age groups, of Indian or Chinese ethnicity, and who are self-employed were more likely to be infected with high-risk HPV.
CONCLUSION: Targeted and robust strategies to reach identified high-risk groups are needed in Malaysia. In addition, the registry has the potential to be expanded for an improved cervical cancer elimination plan.
TRIAL REGISTRATION: Trial registration number: NMRR ID-22-00187-DJU.
METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.
RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population.
CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.
PURPOSE: We compared the frequencies of potentially functional CD38 gene single nucleotide polymorphisms rs1130169 (T > C) in 86 healthy controls and 90 colorectal cancer (CRC) cases to assess their association with cancer risk and CD38 gene expression.
RESULTS: The association between allele C rs1130169 and CRC risk was observed. Allele C was also significantly correlated with an increased CD38 mRNA level and CD38 positive cell percentages in peripheral blood of healthy controls that could be a possible explanation for CRC risk in C allele carriers. In peripheral blood of CRC patients CD38 mRNA and serum soluble CD38 protein levels significantly differed from those in healthy controls. Calculation of the CD38 full-length and with the third exon deletion mRNA ratio in corresponding samples showed that the mRNA isoform ratio was significantly higher in CRC cases than in controls. It suggests that alternative splicing regulates elevation of CD38 full-length mRNA level in peripheral blood of CRC patients. We also have observed higher expression levels of CD38 full-length mRNA in peripheral blood of CRC patients with lymph node metastases compared to patients without metastases.
CONCLUSION: This study indicated biological significance of rs1130169 variations that can alter differences in CRC risk by regulating CD38 gene expression.
METHODS: Forty male Sprague Dawley rats were randomly divided into five groups: (1) healthy control, (2) Alzheimer's control, (3) endurance training, (4) crocin consumption, and (5) endurance training + crocin. Alzheimer's induction was achieved in groups 2-5 through intraperitoneal injection of 8 mg/kg TMT. Rats in groups 3 and 5 engaged in treadmill running three sessions per week, 15-30 min per session, at a speed of 15-20 m/min for eight weeks, and groups 4 and 5 received daily crocin supplementation of 25 mg/kg.
RESULTS: Alzheimer's induction with TMT showed significant reduction in memory, learning, NGF, BDNF, and TrkB gene expression, and increase in tau gene expression (all p
METHODS: The proliferative effect of the identified protein on MCF-7 cells that interacted non-adhesively with BMSCs pre-treated with pioglitazone and/or rosiglitazone was evaluated using cell culture inserts and conditioned media. The mRNA expression of proliferation and lipid accumulation markers was also evaluated in the interacted MCF-7 cells by reverse transcription-quantitative PCR. Finally, the correlation between the identified protein and fibroblast growth factor 4 (FGF-4) protein in the conditioned media of the pre-treated BMSCs was evaluated by ELISA.
RESULTS: The present study identified vimentin as the specific protein among the complex intracellular proteins that likely plays a role in MCF-7 cell proliferation when the breast cancer cells interacted non-adhesively with BMSCs pre-treated with a combination of pioglitazone and rosiglitazone. The inhibition of this protein promoted the proliferation of MCF-7 cells when the breast cancer cells interacted with pre-treated BMSCs. Gene expression analysis indicated that pre-treatment of BMSCs with a combination of pioglitazone and rosiglitazone decreased the mRNA expression of Ki67 and proliferating cell nuclear antigen in MCF-7 cells. The pre-treatment did not induce mRNA expression of PPARγ, which is a sign of lipid accumulation. The level of vimentin protein was also associated with the FGF-4 protein expression level in the conditioned media of the pre-treated BMSCs. Bioinformatics analysis revealed that vimentin regulated the expression of FGF-4 through its interaction with SRY-box 2 and POU class 5 homeobox 1.
CONCLUSIONS: The present study identified a novel intracellular protein that may represent the promising target in pre-treated BMSCs to decrease the proliferation of breast cancer MCF-7 cells for human health and wellness.